MedWorm: Ataxia

Diffuse pulmonary uptake on FDG-PET with normal CT diagnosed as intravascular large B-cell lymphoma: a case report and a discussion of the causes of diffuse FDG uptake in the lungs.

Cancer Imaging — Wed, 08 Feb 2012 00:30:02 +0100

Authors: Wagner T, Brechemier D, Dugert E, Le Guellec S, Julian A, Hitzel A, Beyne-Rauzy O Abstract A 71-year-old woman was admitted to our hospital with asthenia, weight loss, fever, cognitive impairment and shortness of breath. Physical examination showed hemiparesis and cerebellar ataxia. There was no superficial lymphadenopathy. Blood tests showed raised levels of C-reactive protein and lactate dehydrogenase. Bone marrow aspiration and biopsy were negative. [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) showed intense uptake within a right apical nodule and intense and diffuse uptake of FDG in the lungs without corresponding structural CT abnormality. Lung biopsy showed intravascular large B-cell lymphoma (IVLBCL). FDG-PET findings i...

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What Are the Major Diseases Involving Copper Metabolism?

PediatricEducation.org — Mon, 06 Feb 2012 00:08:49 +0100

Discussion Nutritional problems can occur in all parts of the world and in all socioeconomic strata. Caloric and/or protein inadequacy unfortunately plagues too many people because of inadequate supplies or availability. Supplemental food programs around the world attempt to provide appropriate nutrition, but can be stymied because of war, political instability, economic instability and many other social factors. The most common specific nutrient deficiencies are iron and Vitamin D deficiencies. Minerals important for essential nutrition include copper, iodine, selenium and zinc. A typical mixed diet usually provides enough minerals. In the United States, mineral deficiencies are usually uncommon unless there is an underlying disease process or abnormal food restrictions or diet. Vegan an...

Wernekink commissure syndrome: a rare midbrain syndrome

Neurological Sciences — Fri, 03 Feb 2012 17:52:59 +0100

We present two cases of the Wernekink commissure syndrome with acute onset of bilateral cerebellar dysfunction confirmed by magnetic resonance imaging. One patient presented internuclear ophthalmoplegia, but neither showed palatal tremor. It is notable that the bilateral cerebellar dysfunction may be ascribed to midbrain lesion involving the Wernekink commissure, and it may be the sole manifestation of the midbrain lesion. Content Type Journal ArticleCategory Case ReportPages 1-3DOI 10.1007/s10072-012-0966-4Authors Huayan Liu, Department of Neurology, First Affiliated Hospital, China Medical University, No.155, North Nanjing Street, 110001 Shenyang, ChinaLei Qiao, Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang, ChinaZhiyi He, Department of N...

Identification of Delta/notch‐like EGF‐related receptor (DNER) as the Tr antigen in paraneoplastic cerebellar degeneration

Annals of Neurology — Wed, 01 Feb 2012 05:00:00 +0100

AbstractObjective:Anti‐Tr is one of the better described autoantibodies in paraneoplastic cerebellar degeneration (PCD) combined with Hodgkin lymphoma (HL), however the Tr antigen remains unidentified.Methods:We used immunoprecipitation of total rat brain extract followed by mass spectrometry to identify the antigen recognized by anti‐Tr positive sera. By Western blotting and cell‐based assays we tested a total of 12 anti‐Tr positive and 191 control sera and determined the region of the epitope recognized by the anti‐Tr antibodies. Deletion and mutant constructs were generated to further map the antigenic region.Results:Mass spectrometry analysis of immuno‐purified rat brain extract using 4 different anti‐Tr positive sera led to the identification of Delta/Notch‐like epider...

Clinical, Genetic, and Therapeutic Diversity in 2 Patients With Severe Mevalonate Kinase Deficiency

PEDIATRICS — Wed, 01 Feb 2012 05:00:00 +0100

Mevalonic aciduria (MA) represents the severest form of mevalonate kinase deficiency due to recessively inherited, loss-of-function MVK mutations. MA is an early-onset disorder characterized by a marked failure to thrive, diverse neurologic symptoms, dysmorphic features, and recurrent febrile episodes. However, significant clinical differences have been reported in the few cases published to date. Here we describe 2 unrelated Spanish patients with MA, emphasizing the clinical heterogeneity observed. One patient presented with the severe classic MA phenotype due to the homozygous p.Ile-268-Thr MVK genotype, with a poor response to conventional treatments. However, the anti-interleukin 1 agent anakinra in this patient resulted in improvement in many clinical and laboratory parameters. The se...

Evaluation of Levetiracetam as Adjunctive Treatment for Refractory Canine Epilepsy: A Randomized, Placebo‐Controlled, Crossover Trial

Journal of Veterinary Internal Medicine — Wed, 01 Feb 2012 05:00:00 +0100

Conclusions and Clinical ImportanceAdjunctive treatment with LEV appears safe in epileptic dogs. Efficacy of LEV over placebo was not demonstrated, although the power of the study was limited. Further evaluation of LEV as treatment for epilepsy in dogs is warranted. (Source: Journal of Veterinary Internal Medicine)

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HER2/HER3 Signaling Regulates NK Cell-Mediated Cytotoxicity via MHC Class I Chain-Related Molecule A and B Expression in Human Breast Cancer Cell Lines.

Journal of Immunology — Wed, 01 Feb 2012 05:00:00 +0100

In this study, we demonstrate that HER2/HER3 signaling regulates the expression of MHC class I-related chain A and B (MICA and MICB) in breast cancer cell lines. The MICA and MICB (MICA/B) molecules act as key ligands for the activating receptor NK group 2, member D (NKG2D) and promote NK cell-mediated recognition and cytolysis. Genetic silencing of HER3 but not HER2 downregulated the expression of MICA/B, and HER3 overexpression significantly enhanced MICA expression. Among the major pathways activated by HER2/HER3 signaling, the PI3K/AKT pathway was shown to predominantly regulate MICA/B expression. Treatment with the HER3-specific ligand neuregulin 1β promoted the expression in a process that was antagonized by pharmacological and genetic interference with HER3 but not by the ataxia-te...

Spinocerebellar ataxia type 1 (SCA1): New pathoanatomical and clinico‐pathological insights

Neuropathology and Applied Neurobiology — Wed, 01 Feb 2012 05:00:00 +0100

Conclusions: These findings show for the first time that the extent and severity of brain damage in SCA1 is very similar to that of clinically closely related spinocerebellar ataxias (i.e. SCA2, SCA3 and SCA7). They offer suitable explanations for poorly understood SCA1 disease symptoms and will facilitate the interpretation of further morphological and experimental SCA1 studies.© 2012 The Authors. Neuropathology and Applied Neurobiology © 2012 British Neuropathological Society (Source: Neuropathology and Applied Neurobiology)

Mitochondrial dysfunction and Purkinje cell loss in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) [Medical Sciences]

Proceedings of the National Academy of Sciences — Tue, 31 Jan 2012 05:00:00 +0100

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood-onset neurological disease resulting from mutations in the SACS gene encoding sacsin, a 4,579-aa protein of unknown function. Originally identified as a founder disease in Québec, ARSACS is now recognized worldwide. Prominent features include pyramidal spasticity and cerebellar ataxia, but the underlying pathology and pathophysiological mechanisms are unknown. We have generated an animal model for ARSACS, sacsin knockout mice, that display age-dependent neurodegeneration of cerebellar Purkinje cells. To explore the pathophysiological basis for this observation, we examined the cell biological properties of sacsin. We show that sacsin localizes to mitochondria in non-neuronal cells and primary neurons and tha...

Altered Kv3.3 Channel Gating in Early Onset Spinocerebellar Ataxia Type 13.

The Journal of Physiology — Mon, 30 Jan 2012 05:00:00 +0100

We report that one R420H subunit and at least one R423H subunit can co-assemble with the wild type protein to form active channels. The functional properties of channels containing R420H and wild type subunits strongly resemble those of wild type alone. In contrast, channels containing R423H and wild type subunits show significantly altered gating, including a hyperpolarized shift in the voltage dependence of activation, slower activation, and modestly slower deactivation. Notably, these effects resemble the modified gating seen in channels containing a mixture of F448L and wild type subunits, although the F448L subunit slows deactivation more dramatically than the R423H subunit. Our results suggest that the clinical severity of R423H reflects its dual dominant negative and dominant gain o...

Is cerebral white matter involvement helpful in the diagnosis of dentatorubral-pallidoluysian atrophy?

Journal of Neurology — Fri, 27 Jan 2012 17:56:41 +0100

We describe three cases of genetically confirmed DRPLA that developed changes in cerebral white matter in the early stage of middle-aged patients. Our results of our study indicate that cerebral white matter changes are not rare in DRPLA and might be helpful for differentiation in ataxia patients with brainstem and cerebellum atrophy. Content Type Journal ArticleCategory Original CommunicationPages 1-4DOI 10.1007/s00415-011-6401-6Authors Won Tae Yoon, Department of Neurology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaJinyoung Youn, Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul, 135-710 Republic of KoreaJin Whan Cho, Department of Neurology, Samsung M...

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Effect of sub-acute exposure to acrylamide on GABAergic neurons and astrocytes in weaning rat cerebellum

Toxicology and Industrial Health current issue — Fri, 27 Jan 2012 05:00:00 +0100

In this study, we tested whether ACR would affect cerebellar function through the regulation of gamma-aminobutyric acid (GABA) and glial fibrillary acidic protein (GFAP) expression in cerebellum. Weaning male Sprague-Dawley rats were gavaged with ACR (5, 15, 30 mg/kg, 5 days per week) or saline for 4 weeks. Effects of ACR on the cerebellum were observed. For the 5 mg/kg group, no obvious change was observed, whereas moderate and severe ataxia were observed in the 15 mg/kg and 30 mg/kg groups, respectively. For the 15 mg/kg and 30 mg/kg groups, cerebellum concentrations of glutamate and GABA were dose-dependently decreased and increased, respectively. Moreover, the expression of GABA, the GABAergic presynaptic marker glutamate acid decarboxylase-65 (GAD65) and GFAP were significantly increa...

Mutations in rare ataxia genes are uncommon causes of sporadic cerebellar ataxia

Movement Disorders — Fri, 27 Jan 2012 05:00:00 +0100

Conclusions:The rare genetic ataxias examined here do not significantly contribute to sporadic cerebellar ataxia in our tertiary care population. © 2012 Movement Disorder Society (Source: Movement Disorders)

Unilateral thalamic stimulation safely improved fragile X–associated tremor ataxia: A case report

Movement Disorders — Fri, 27 Jan 2012 05:00:00 +0100

(Source: Movement Disorders)

PI3K-like kinases restrain Pim gene expression in endothelial cells

Journal of Huazhong University of Science and Technology -- Medical Sciences -- — Thu, 26 Jan 2012 16:50:00 +0100

Summary Pim kinases contribute to tumor formation and development of lymphoma, which shows enhanced DNA replication, DNA recombination and repair. Endothelial cells^(ECs) express all the three members of Pim kinase gene family. We hypothesized that DNA repair gene would regulate Pim expression in ECs. Human umbilical vein endothelial cells (HUVECs) were isolated and maintained in M199 culture medium. The cellular distribution of Pim-3 in ECs was determined by immunofluorescent staining. The siRNA fragments were synthesized and transfected by using Lipofectamine LTX. The total cellular RNA was extracted from the cells by using Trizol reagent. cDNAs were quantified by semi-quantity PCR. The effects of LY294002 and wortmannin on RNA stability in ECs were also examined. Our da...

Lack of ataxia telangiectasia mutated kinase induces structural and functional changes in the heart: role in β‐adrenergic receptor‐stimulated apoptosis

Experimental Physiology — Thu, 26 Jan 2012 05:00:00 +0100

Ataxia telangiectasia mutated kinase (ATM) is involved in cell cycle checkpoints, DNA repair and apoptosis. β‐Adrenergic receptor (β‐AR) stimulation induces cardiac myocyte apoptosis. Here we analysed basal myocardial structure and function in ATM knockout (KO) mice and tested the hypothesis that ATM modulates β‐AR‐stimulated myocyte apoptosis. Left ventricular (LV) structure and function, myocyte apoptosis, fibrosis and expression of fibrosis‐, hypertrophy‐ and apoptosis‐related proteins were examined in wild‐type (WT) and KO mice with or without l‐isoprenaline treatment for 24 h. Body and heart weights were lower in KO mice. M‐Mode echocardiography showed reduced septal wall thicknesses and LV diameters in KO mice. Doppler echocardiography showed an increased ratio...

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A practical approach to late-onset cerebellar ataxia: putting the disorder with lack of order into order.

Practical Neurology — Thu, 26 Jan 2012 03:31:35 +0100

Authors: van Gaalen J, van de Warrenburg BP Abstract The clinical management of cerebellar ataxia is challenging, mainly because ataxia is a symptom of many neurological diseases. Many types of ataxia disorders are genetic and some are extremely rare. Here, the authors suggest a diagnostic approach to ataxia developed around a case of sporadic, late-onset, slowly progressive ataxia. Clinical information such as age of onset, rate of progression, family history and certain non-cerebellar features can narrow the differential diagnosis. Brain MRI is almost obligatory and may reveal valuable diagnostic clues. Having ruled out structural lesions, the two other most common diagnoses are inflammatory and degenerative (including genetic) disorders. Although only a minority of underlying di...

Clinical Manifestations of Foot‐and‐Mouth Disease During the 2010/2011 Epidemic in the Republic of Korea

Transboundary and Emerging Diseases — Wed, 25 Jan 2012 05:00:00 +0100

In this study, the clinical signs of FMD were described on the basis of the subjective observations by the farm workers. The present results highlight the clinical signs expected on specific body parts of different types of susceptible animals, and therefore, they may be useful for generating public awareness, particularly among farm workers, as well as for early detection of future FMD outbreaks. (Source: Transboundary and Emerging Diseases)

Autophagy-dependent senescence in response to DNA damage and chronic apoptotic stress.

Autophagy — Tue, 24 Jan 2012 09:56:09 +0100

Authors: Singh K, Matsuyama S, Drazba JA, Almasan A Abstract Autophagy regulates cell survival and cell death upon various cellular stresses, yet the molecular signaling events involved are not well defined. Here, we established the function of a proteolytic Cyclin E fragment (p18-CycE) in DNA damage-induced autophagy, apoptosis, and senescence. p18-CycE was identified in hematopoietic cells undergoing DNA damage-induced apoptosis. In epithelial cells exposed to DNA damage, chronic but not transient expression of p18-CycE leads to higher turnover of LC3 I/II and increased emergence of autophagosomes and autolysosomes. Levels of p18-CycE, which was generated by proteolytic cleavage of endogenous Cyclin E, were greatly increased by chloroquine and correlated with LC 3II conversion. P...

Movement disorders: role of imaging in diagnosis

Journal of Magnetic Resonance Imaging — Tue, 24 Jan 2012 08:15:38 +0100

AbstractMagnetic resonance imaging (MRI and single‐photon emission computed tomography (SPECT) have a considerable role in the diagnosis of the single patient with movement disorders. Conventional MRI demonstrates symptomatic causes of parkinsonism but does not show any specific finding in Parkinson's disease (PD). However, SPECT using tracers of the dopamine transporter (DAT) demonstrates an asymmetric decrease of the uptake in the putamen and caudate from the earliest clinical stages. In other degenerative forms of parkinsonism, including progressive supranuclear palsy (PSP), multisystem atrophy (MSA), and corticobasal degeneration (CBD), MRI reveals characteristic patterns of regional atrophy combined with signal changes or microstructural changes in the basal ganglia, pons, middle an...

The adverse event profile of pregabalin across different disorders: a meta-analysis

European Journal of Clinical Pharmacology — Tue, 24 Jan 2012 07:20:02 +0100

Conclusions Although drug-resistant partial epilepsy is associated with a higher probability of developing vestibulo-cerebellar AEs, the risk for PGB toxicity does not differ across distinct disorders. Content Type Journal ArticleCategory Clinical TrialPages 1-10DOI 10.1007/s00228-012-1213-xAuthors Gaetano Zaccara, U.O. Neurologia, Azienda Sanitaria di Firenze, Firenze, ItalyPiero Perucca, Montreal Neurological Institute, McGill University, Montreal, Quebec, CanadaPier Franco Gangemi, Anffas Rehabilitation Institute, Firenze, Italy Journal European Journal of Clinical PharmacologyOnline ISSN 1432-1041Print ISSN 0031-6970 (Source: European Journal of Clinical Pharmacology)

Middle Cerebellar Peduncles and Pontine T2 Hypointensities in ARSACS

Journal of Neuroimaging — Mon, 23 Jan 2012 05:00:00 +0100

CONCLUSIONNot only pontine but also middle cerebellar peduncle hypointensity lesions observed in T2‐weighted and FLAIR images could be specific findings for ARSACS even in cases with variable clinical phenotypes. J Neuroimaging 2012;XX:1–4. (Source: Journal of Neuroimaging)

Drugs of abuse (amfetamines, BZP, cannabis, cocaine, GHB, LSD)

Medicine — Sat, 21 Jan 2012 13:58:54 +0100

Abstract: The features of amfetamine poisoning are related predominantly to stimulation of central and peripheral adrenergic receptors, and in severe cases, excitability, agitation, paranoid delusions, hallucinations with violent behaviour, hypertonia and hyperreflexia develop. Convulsions, rhabdomyolysis, hyperthermia, intracerebral haemorrhage and cardiac arrhythmias are less common. In addition, hyperthermia and hyponatraemia are features of severe MDMA toxicity.Benzylpiperazine (BZP) has stimulant and amfetamine-like properties. Those severely poisoned may develop seizures, collapse, hyperthermia, myoclonic jerks, extrapyramidal features and respiratory failure.Features of cannabis use include euphoria, distorted and heightened images, colours and sounds, altered tactile sensations, im...

Genetics of the Dominant Ataxias

Seminars in Neurology — Sat, 21 Jan 2012 05:00:00 +0100

Semin Neurol 2011; 31: 461-469DOI: 10.1055/s-0031-1299785ABSTRACTThe relevant clinical, genetic, and cell biologic aspects of the dominantly inherited spinocerebellar ataxias (SCAs) are reviewed in this article. SCAs are diseases of the entire nervous system; in addition to cerebellar ataxia, the central (but not obligate) disease feature, many noncerebellar complications can be present as well. There are over 35 genetic subtypes: although those caused by expanded CAG repeats are still the more common ones, the majority of the recent SCAs have been caused by more conventional mutations. Genotype–phenotype correlations do exist and are most clear for the repeat expansion, where repeat length partially explains age at onset, disease severity and progression, and the core clinical phenotype...

Genetics of Hereditary Spastic Paraplegias

Seminars in Neurology — Sat, 21 Jan 2012 05:00:00 +0100

Semin Neurol 2011; 31: 484-493DOI: 10.1055/s-0031-1299787ABSTRACTHereditary spastic paraplegias (HSPs) are clinically and genetically highly heterogeneous. The key symptom of spastic paraparesis of lower limbs can be complicated by a variety of signs and symptoms including cognitive impairment, optic atrophy, cerebellar ataxia, peripheral nerve involvement, or seizures. At least 48 loci have been identified, termed SPG1–SPG48. Ten genes for autosomal dominant HSP are currently known, SPG4 being by far the most common subtype accounting for ∼50% of cases. SPG3 is especially common in young-onset cases. Autosomal recessive HSP seems to be even more heterogeneous. The known 12 autosomal recessive HSP genes collectively explain about one third of cases only. The most common causes for pure...

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Dbf4 Is Direct Substrate of ATM and ATR [Cell Biology]

Journal of Biological Chemistry — Fri, 20 Jan 2012 05:00:00 +0100

Dbf4/Cdc7 (Dbf4-dependent kinase (DDK)) is activated at the onset of S-phase, and its kinase activity is required for DNA replication initiation from each origin. We showed that DDK is an important target for the S-phase checkpoint in mammalian cells to suppress replication initiation and to protect replication forks. We demonstrated that ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) proteins directly phosphorylate Dbf4 in response to ionizing radiation and replication stress. We identified novel ATM/ATR phosphorylation sites on Dbf4 and showed that ATM/ATR-mediated phosphorylation of Dbf4 is critical for the intra-S-phase checkpoint to inhibit DNA replication. The kinase activity of DDK, which is not suppressed upon DNA damage, is required for fork p...

Administration of ON 01210.Na after exposure to ionizing radiation protects bone marrow cells by attenuating DNA damage response

Radiation Oncology — Fri, 20 Jan 2012 05:00:00 +0100

Conclusions: ON 01210.Na treatment significantly mitigated the hematopoietic toxicity induced by a sub-lethal radiation dose. Mechanistically, attenuation of ATM-p53 mediated DNA damage response by ON 01210.Na is contributing to the mitigation of radiation-induced hematopoietic toxicity. (Source: Radiation Oncology)

ENU mutagenesis in mice identifies candidate genes for hypogonadism

Mammalian Genome — Thu, 19 Jan 2012 06:55:00 +0100

Abstract Genome-wide mutagenesis was performed in mice to identify candidate genes for male infertility, for which the predominant causes remain idiopathic. Mice were mutagenized using N-ethyl-N-nitrosourea (ENU), bred, and screened for phenotypes associated with the male urogenital system. Fifteen heritable lines were isolated and chromosomal loci were assigned using low-density genome-wide SNP arrays. Ten of the 15 lines were pursued further using higher-resolution SNP analysis to narrow the candidate gene regions. Exon sequencing of candidate genes identified mutations in mice with cystic kidneys (Bicc1), cryptorchidism (Rxfp2), restricted germ cell deficiency (Plk4), and severe germ cell deficiency (Prdm9). In two other lines with severe hypogonadism, candidate sequencin...

Principal Component Analysis of Cerebellar Shape on MRI Separates SCA Types 2 and 6 into Two Archetypal Modes of Degeneration.

Cerebellum — Thu, 19 Jan 2012 05:00:00 +0100

Authors: Jung BC, Choi SI, Du AX, Cuzzocreo JL, Geng ZZ, Ying HS, Perlman SL, Toga AW, Prince JL, Ying SH Abstract Although "cerebellar ataxia" is often used in reference to a disease process, presumably there are different underlying pathogenetic mechanisms for different subtypes. Indeed, spinocerebellar ataxia (SCA) types 2 and 6 demonstrate complementary phenotypes, thus predicting a different anatomic pattern of degeneration. Here, we show that an unsupervised classification method, based on principal component analysis (PCA) of cerebellar shape characteristics, can be used to separate SCA2 and SCA6 into two classes, which may represent disease-specific archetypes. Patients with SCA2 (n = 11) and SCA6 (n = 7) were compared against controls (n = 15) using PCA to clas...

Magnetic Resonance Imaging Lesions in the Central Nervous System of a Dog with Canine Monocytic Ehrlichiosis

Diagnostic and Therapeutic Endoscopy — Wed, 18 Jan 2012 12:06:54 +0100

This report describes MRI central nervous system findings in a dog with ehrlichiosis. (Source: Diagnostic and Therapeutic Endoscopy)

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[Life-threatening complication of schizophrenia].

Praxis — Wed, 18 Jan 2012 05:00:00 +0100

Authors: Felix O, Felleiter P, Sturzenegger M Abstract The Wernicke Encephalopathy (WE) as a result of a (sub)acute thiamine deficiency remains, unfortunately, still under-diagnosed, especially among non-alcoholics. It should be considered in each occurrence of delirium as well as in any ocular motor disorder and ataxia, in particular if there is a history of weight loss with or without gastrointestinal symptoms. In cases with suspected WE an immediate intravenous substitution of 3×200 mg/d is recommended. PMID: 22252595 [PubMed - in process] (Source: Praxis)

Sleep-Disordered Breathing in Neurodegenerative Diseases

Current Neurology and Neuroscience Reports — Tue, 17 Jan 2012 07:06:32 +0100

Abstract Sleep disorders are common in neurodegenerative diseases such as Parkinson’s disease (PD), multiple system atrophy (MSA), amyotrophic lateral sclerosis (ALS), hereditary ataxias, and Alzheimer’s disease (AD). Type, frequency, and severity of sleep disturbances vary depending on each of these diseases. Cell loss of the brainstem nuclei that modulates respiration, and dysfunction of bulbar and diaphragmatic muscles increase the risk for sleep-disordered breathing (SDB) in MSA and ALS. The most relevant SDB in MSA is stridor, whereas in ALS nocturnal hypoventilation due to diaphragmatic weakness is the most common sleep breathing abnormality. Stridor and nocturnal hypoventilation are associated with reduced survival in MSA and ALS. In contrast, sleep apnea seems ...

Scripps research scientists create novel RNA repair technology

EurekAlert! - Biology — Tue, 17 Jan 2012 05:00:00 +0100

(Scripps Research Institute) Scientists from the Florida campus of the Scripps Research Institute have identified a compound that can help repair a specific type of defect in RNA, a type of genetic material. The methods in the new study could accelerate the development of therapeutics to treat a variety of incurable diseases such as Huntington's disease, Spinocerebellar ataxia, and Kennedy disease. (Source: EurekAlert! - Biology)

Disseminated protothecosis diagnosed by evaluation of CSF in a dog

Veterinary Clinical Pathology — Tue, 17 Jan 2012 05:00:00 +0100

AbstractA 5‐year‐old female spayed Shetland Sheepdog Mix dog was evaluated for a history of recent seizure activity, progressive hind limb ataxia, polyuria, and polydipsia and no history of gastrointestinal signs. Physical examination findings included conscious proprioceptive deficits, ataxia, and anterior uveitis along with a hypermature cataract in the right eye. Results of a CBC, serum biochemical profile, urinalysis, and computed tomography scan of the brain were unremarkable. Cerebrospinal fluid (CSF) analysis revealed marked eosinophilic pleocytosis and rare organisms consistent with Prototheca spp within neutrophils and macrophages. On postmortem histologic examination, mononuclear inflammation and numerous intralesional algal organisms, similar to those seen on the cytologic p...

The E3 ubiquitin ligase Mule acts through the ATM-p53 axis to maintain B lymphocyte homeostasis

The Journal of Experimental Medicine — Mon, 16 Jan 2012 05:00:00 +0100

Cellular homeostasis is controlled by pathways that balance cell death with survival. Mcl-1 ubiquitin ligase E3 (Mule) is an E3 ubiquitin ligase that targets the proapoptotic molecule p53 for polyubiquitination and degradation. To elucidate the role of Mule in B lymphocyte homeostasis, B cell–specific Mule knockout (BMKO) mice were generated using the Cre–LoxP recombination system. Analysis of BMKO mice showed that Mule was essential for B cell development, proliferation, homeostasis, and humoral immune responses. p53 transactivation was increased by two- to fourfold in Mule-deficient B cells at steady state. Genetic ablation of p53 in BMKO mice restored B cell development, proliferation, and homeostasis. p53 protein was increased in resting Mule-deficient mouse embryonic fibro...

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Ataxic sensory neuronopathy in a patient with systemic lupus erythematosus.

Lupus — Mon, 16 Jan 2012 05:00:00 +0100

We report the case of a young woman who presented with ASN, characterized by sensory ataxia, with elevated antinuclear antibodies, leukopenia and anemia; she fulfilled the diagnostic criteria for SLE about 7 years after the onset of sensory ataxia. Our case points out that ASN may be the initial presenting feature of SLE. SLE should be included in the differential diagnosis of ASN, especially in patients of young age. PMID: 22249650 [PubMed - as supplied by publisher] (Source: Lupus)

Gulf War Syndrome as a part of the autoimmune (autoinflammatory) syndrome induced by adjuvant (ASIA).

Lupus — Sun, 15 Jan 2012 14:30:03 +0100

Authors: Israeli E Abstract Gulf War syndrome (GWS) is a multi-symptom condition comprising a variety of signs and symptoms described in the literature, which not been fully resolved. The various symptoms of the condition include muscle fatigue and tiredness, malaise, myalgia, impaired cognition, ataxia, diarrhoea, bladder dysfunction, sweating disturbances, headaches, fever, arthralgia, skin rashes, and gastrointestinal and sleep disturbances. In addition, excessive chemical sensitivity and odour intolerance is reported. The aetiology of the condition is unclear, but many reviews and epidemiological analyses suggest association with pyridostigmine bromide (PB), certain vaccination regimes, a variety of possible chemical exposures, including smoke from oil-well fires or depleted ur...

Valproate-induced encephalopathy with predominant pancerebellar syndrome

Indian Journal of Pharmacology — Sat, 14 Jan 2012 05:00:00 +0100

Rajesh Verma, Prakash KoriIndian Journal of Pharmacology 2012 44(1):129-130Valproate-induced hyperammonemic encephalopathy is a rare event clinically characterized by impaired sensorium, vomiting, headache, seizures and focal neurological deficits. The pathogenesis of this dreadful complication is not well understood, although hyperammonemia has been implicated in causation of encephalopathy. In this submission, we have highlighted a case of valproate-induced encephalopathy who presented mainly with bilateral cerebellar features and generalized slowing on electroencephalogram. High index of suspicion of valproate-induced hyperammonemic encephalopathy is required if diffuse ataxia is present as it is a potentially reversible clinical disorder. (Source: Indian Journal of Pharmacology)

Oxidative stress induces an ATM-independent senescence pathway through p38 MAPK-mediated lamin B1 accumulation

The EMBO Journal AOP — Fri, 13 Jan 2012 05:00:00 +0100

Authors: Aurelia Barascu, Catherine Le Chalony, Gaëlle Pennarun, Diane Genet, Naima Imam, Bernard Lopez & Pascale Bertrand (Source: The EMBO Journal AOP)

Iron dysregulation in movement disorders.

Neurobiology of Disease — Thu, 12 Jan 2012 05:00:00 +0100

Authors: Dusek P, Jankovic J, Le W Abstract Iron is an essential element necessary for energy production, DNA and neurotransmitter synthesis, myelination and phospholipid metabolism. Neurodegeneration with brain iron accumulation (NBIA) involves several genetic disorders, two of which, aceruloplasminemia and neuroferritinopathy, are caused by mutations in genes directly involved in iron metabolic pathway, and others, such as pantothenate-kinase 2, phospholipase-A2 and fatty acid 2-hydroxylase associated neurodegeneration, are caused by mutations in genes coding for proteins involved in phospholipid metabolism. Phospholipids are major constituents of myelin and iron accumulation has been linked to myelin derangements. Another group of NBIAs is caused by mutations in lysosomal enzyme...

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Legionellosis presenting as singultus and external ophthalmoplegia

Neurological Sciences — Tue, 10 Jan 2012 16:57:06 +0100

We report a 71-year-old man with legionellosis, who presented with abducens nerve palsy, singultus, confusion, memory impairment, ataxia, and hyporeflexia. Legionella pneumonia was diagnosed on the basis of detection of Legionella pneumophila antigen in the urine. The cerebrospinal fluid was negative for the antigen and antibody, but an oligoclonal band was detected, and the IgG index was elevated. It was speculated that an undetermined immune-mediated mechanism had contributed to the development of the neurological manifestations. Content Type Journal ArticleCategory Case ReportPages 1-3DOI 10.1007/s10072-011-0927-3Authors Shingo Konno, Division of Neurology, Department of Internal Medicine, Toho University Ohashi Medical Center, 2-17-6 Ohashi, Meguro-ku, Tokyo, 153-8515 JapanHa...

SRD5A3-CDG: A patient with a novel mutation.

European Journal of Paediatric Neurology — Tue, 10 Jan 2012 05:00:00 +0100

We report on a patient with SRD5A3-CDG carrying a novel (homozygous) mutation. The diagnostic features of this novel inborn error of glycosylation are psychomotor retardation, nystagmus, visual impairment due to variable eye malformations, cerebellar abnormalities/ataxia, and often ichthyosiform skin lesions. PMID: 22240719 [PubMed - as supplied by publisher] (Source: European Journal of Paediatric Neurology)

High Width Variability during Spiral Drawing: Further Evidence of Cerebellar Dysfunction in Essential Tremor.

Cerebellum — Tue, 10 Jan 2012 05:00:00 +0100

Authors: Louis ED, Gillman A, Boschung S, Hess CW, Yu Q, Pullman SL Abstract Essential tremor (ET) is among the most prevalent neurological diseases, yet the location of the primary disease substrate continues to be a matter of debate. The presence of intention tremor and mild gait ataxia suggests an underlying abnormality of the cerebellum and/or cerebellar pathways. Uncovering additional signs of cerebellar dysfunction would further substantiate the proposition that ET is a disease of the cerebellar system. We evaluated 145 ET cases and 34 normal controls clinically and by computerized spiral analysis. Spiral analysis is a program that objectively characterizes kinematic and physiologic features of hand-drawn spirals using specific calculated spiral indices that correlate with sp...

Phenotypic and genotypic variability in Alpers syndrome.

European Journal of Paediatric Neurology — Mon, 09 Jan 2012 05:00:00 +0100

CONCLUSION: Alpers syndrome is a heterogeneous syndrome that should be considered in patients with early-onset progressive cortical encephalopathy regardless of liver involvement. The phenotype is different depending on the presence or absence of POLG1 mutations. PMID: 22237560 [PubMed - as supplied by publisher] (Source: European Journal of Paediatric Neurology)

Novel Hypomyelinating Leukoencephalopathy Affecting Early Myelinating Structures [Observation]

Archives of Neurology — Mon, 09 Jan 2012 05:00:00 +0100

Conclusions The patients share a striking pattern of MRI abnormalities and have a similar clinical picture, suggesting that they have the same disorder. The hypomyelination in this disorder specifically occurs in structures that normally myelinate early. We hypothesize that the disease is caused by a defect in a gene involved in early myelination. (Source: Archives of Neurology)

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Topiramate Effect in Opsoclonus-Myoclonus-Ataxia Syndrome [Images in Neurology]

Archives of Neurology — Mon, 09 Jan 2012 05:00:00 +0100

(Source: Archives of Neurology)

Temperature profoundly affects ataxin-3 fibrillogenesis.

Biochimie — Sat, 07 Jan 2012 05:00:00 +0100

We report here that AT3Q24, when gradually heated up to 85 °C, undergoes aggregation similar to that observed at 37 °C; in contrast, AT3Q55 only generates large, amorphous aggregates. We propose a possible interpretation of the mechanism by which temperature affects the outcome of fibrillogenesis. PMID: 22234302 [PubMed - as supplied by publisher] (Source: Biochimie)

Mutations in Genomic Integrity Gene Increase Hereditary Pancreatic Cancer Risk

Cancer Network — Fri, 06 Jan 2012 12:00:00 +0100

Inherited mutations in the ataxia telangiectasia mutated (ATM) gene increase the odds of developing pancreatic cancer according to a new study. While there is predisposition for pancreatic cancer with up to 10% of cases occurring among families with a history of the disease, the genetic basis for this had not been previously discovered. (Source: Cancer Network)

An unusual case of miller fisher syndrome presenting with proptosis and chemosis

Muscle and Nerve — Fri, 06 Jan 2012 05:00:00 +0100

Adult-onset cerebellar ataxia due to mutations in CABC1/ADCK3

Journal of Neurology, Neurosurgery and Psychiatry — Fri, 06 Jan 2012 05:00:00 +0100

Conclusions These observations highlight the importance of screening for a potentially treatable cause, CABC1/ADCK3 mutations, not only in severe childhood-onset ataxia, but also in patients with mild cerebellar ataxia in adult life. (Source: Journal of Neurology, Neurosurgery and Psychiatry)

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Cerebellar-type multiple system atrophy presenting with leucoencephalopathy

Journal of Neurology, Neurosurgery and Psychiatry — Fri, 06 Jan 2012 05:00:00 +0100

In June 2004, a 52-year-old woman was admitted to our department with a walking impairment and scanning speech that had persisted over the previous few months. A neurological examination revealed exclusively cerebellar signs with gait ataxia, slight oculomotor dysfunction and impaired coordination. Known medical and family history were unremarkable up to this point (however, no information could be provided on the patient's father). MRI scans showed a severe cerebellar atrophy of both hemispheres without any additional pathologies. Electrophysiological (evoked potentials) and blood examination, including vitamin E, vitamin B12, antineuronal antibodies and genetic testing for spinocerebellar ataxia genotypes 1, 2, 3 and 6, were negative for pathological findings. Over the following months t...

Murder by poisoned cat stew

The Poison Review — Thu, 05 Jan 2012 20:19:10 +0100

Gelsemium elegans Today’s New York Times reports that the death of Chinese billionaire Long Liyuan last month was caused by poison slipped into the cat-meat hot pot on which he was dining. Mr. Long was having lunch with a local government official, Huang Guang, whose corruption he apparently had discovered and was about to expose. Three people at the luncheon — including Mr. Huang — became sick and were hospitalized. Police now believe that Mr. Huang slipped the toxic herb Gelsemium elegans into the stew, and ate some himself in an attempt to divert suspicion. G. elegans is a flowering plant native to southeast Asia. It is nicknamed “heartbreak grass” because it is commonly used in that area as an agent in suicides. The plant contains several toxins, incl...

Is there delayed gastric emptying in patients with multiple system atrophy? An analysis using the 13C-acetate breath test

Journal of Neurology — Thu, 05 Jan 2012 06:52:09 +0100

Abstract Autonomic failure is one of the criteria according to the second consensus statement for the diagnosis of multiple system atrophy (MSA). Gastrointestinal symptoms are frequent complaints in patients with MSA and may be associated with reduced gastrointestinal motility due to autonomic nervous system dysfunction. However, there are few reports on gastric emptying in patients with MSA. We investigated gastric emptying in 25 patients with MSA, 20 patients with sporadic adult-onset ataxia of unknown etiology (SAOA), and 20 healthy volunteers using the 13C-acetate breath test. Gastric emptying function is estimated by this test as the half-emptying time (HET) and peak time of the 13C-%-dose-excess curve (T max), with expirations collected for 4 h after a test meal...

Tcl1 interacts with Atm and enhances NF-{kappa}B activation in hematologic malignancies

Blood — Thu, 05 Jan 2012 05:00:00 +0100

The T-cell leukemia/lymphoma 1 (TCL1) oncogene is a target of chromosomal translocations and inversions at 14q31.2, and its rearrangement in T cells causes T-cell prolymphocytic leukemias. TCL1 dysregulation in B cells is responsible for the development of an aggressive form of chronic lymphocytic leukemia (CLL), the most common human leukemia. We have investigated the mechanisms underlying the oncogenic functions of Tcl1 protein using a mass spectrometry approach and have identified Atm (ataxia-telangiectasia mutated) as a candidate Tcl1-interacting protein. The Tcl1-Atm complex formation was validated by coimmunoprecipitation experiments. Importantly, we show that the association of Atm with Tcl1 leads to enhanced IBα phosphorylation and ubiquitination and subsequent activation of ...

Genotype–phenotype correlation in interstitial 6q deletions: a report of 12 new cases

Neurogenetics — Wed, 04 Jan 2012 17:00:00 +0100

We report 12 individuals with overlapping, 200-kb to 16.4-Mb interstitial deletions within 6q15q22.33 characterized by microarray-based comparative genomic hybridization to better correlate deletion regions with specific phenotypes. Four individuals have a PW-like phenotype, though only two have deletion of SIM1, the candidate gene for this feature. Therefore, other genes on 6q may contribute to this phenotype including multiple genes on 6q16 and our newly proposed candidate, the transcription cofactor gene VGLL2 on 6q22.2. Two individuals present with movement disorders as a major feature, and ataxia is present in a third. The 4.1-Mb 6q22.1q22.2 critical region for movement disorders includes the cerebellar-expressed candidate gene GOPC. Observed brain malformations include thick cor...

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Phase I dose-escalating study of ES-285 given as a three-hour intravenous infusion every three weeks in patients with advanced malignant solid tumors

Investigational New Drugs — Wed, 04 Jan 2012 06:58:28 +0100

Conclusion Dose level VIII (200 mg/m2) was considered the MTD, and dose level IX (160 mg/m2) was defined as the RD. Limited antitumor activity was observed. Content Type Journal ArticleCategory PHASE I STUDIESPages 1-9DOI 10.1007/s10637-011-9772-8Authors C. Massard, Departement de Médecine, Institut Gustave Roussy, University Paris South XI, SITEP, 39, rue Camille Desmoulins, 94805 Villejuif, FranceR. Salazar, Institut Català d’Oncologia, Barcelona, SpainJ. P. Armand, Departement de Médecine, Institut Gustave Roussy, University Paris South XI, SITEP, 39, rue Camille Desmoulins, 94805 Villejuif, FranceM. Majem, Institut Català d’Oncologia, Barcelona, SpainE. Deutsch, Departement de Médecine, Institut Gustave Roussy, University Paris South XI, SITEP, 39, rue Camille...

Erythropoietin in friedreich ataxia: No effect on frataxin in a randomized controlled trial

Movement Disorders — Wed, 04 Jan 2012 05:00:00 +0100

AbstractBackground:Friedreich ataxia is a rare disease caused by GAA‐trinucleotide‐repeat expansions in the frataxin gene, leading to marked reduction of qualitatively normal frataxin protein. Recently, human recombinant erythropoietin was reported to increase frataxin levels in patients with Friedreich ataxia.Methods:We performed a 6‐month, randomized placebo‐controlled, double‐blind, dose‐response pilot trial to assess the safety and efficacy of erythropoietin in increasing frataxin levels. Sixteen adult patient with Friedreich ataxia were randomly assigned to erythropoietin (n = 11) or matching placebo (n = 5). All patients continued Idebenone treatment (5 mg/kg/day). Treatment consisted of a 6‐month scaling‐up phase, in which erythropoietin was administered intravenousl...

Oncolytic Virus-Mediated Manipulation of DNA Damage Responses: Synergy With Chemotherapy in Killing Glioblastoma Stem Cells

JNCI — Tue, 03 Jan 2012 05:00:00 +0100

Conclusions The combination of G47 and TMZ acts synergistically in killing GSCs through oHSV-mediated manipulation of DNA damage responses. This strategy is highly efficacious in representative preclinical models and warrants clinical translation. (Source: JNCI)

A distinct response to endogenous DNA damage in the development of Nbs1-deficient cortical neurons.

Cell Research — Tue, 03 Jan 2012 05:00:00 +0100

Authors: Li R, Yang YG, Gao Y, Wang ZQ, Tong WM Abstract Microcephaly is a clinical characteristic for human nijmegen breakage syndrome (NBS, mutated in NBS1 gene), a chromosomal instability syndrome. However, the underlying molecular pathogenesis remains elusive. In the present study, we demonstrate that neuronal disruption of NBS (Nbn in mice) causes microcephaly characterized by the reduction of cerebral cortex and corpus callosum, recapitulating neuronal anomalies in human NBS. Nbs1-deficient neocortex shows accumulative endogenous DNA damage and defective activation of Ataxia telangiectasia and Rad3-related (ATR)-Chk1 pathway upon DNA damage. Notably, in contrast to massive apoptotic cell death in Nbs1-deficient cerebella, activation of p53 leads to a defective neuroprogenitor...

Checkpoint kinase 1 (Chk1)-short is a splice variant and endogenous inhibitor of Chk1 that regulates cell cycle and DNA damage checkpoints [Cell Biology]

Proceedings of the National Academy of Sciences — Tue, 03 Jan 2012 05:00:00 +0100

Checkpoint kinase 1 (Chk1) is a key regulator of checkpoint signaling in both the unperturbed cell cycle and DNA damage response. Under these conditions, Chk1 becomes active to prevent premature CDK1 activation and mitotic entry until DNA is properly replicated or repaired. It is unclear how Chk1 activity is controlled in the unperturbed cell cycle. During DNA damage, Chk1 is activated by ataxia telangiectasia and Rad3 related (ATR)-mediated phosphorylation; however, it is not entirely clear how this phosphorylation results in Chk1 activation. Here we report an N-terminally truncated alternative splice variant of Chk1, Chk1-S. Importantly, we show that Chk1-S is an endogenous repressor and regulator of Chk1. In the unperturbed cell cycle, Chk1-S interacts with and antagonizes Chk1 to promo...

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Segmental myoclonus and marked ataxia in a patient of pulmonary tuberculosis

Neurology India — Mon, 02 Jan 2012 05:00:00 +0100

VV Ashraf, Praveenkumar , EK Sureshkumar, Rajeev Anand, Shalini Kuruvilla, AS GirijaNeurology India 2011 59(6):904-906 (Source: Neurology India)

Divergent clinical and neuropathological phenotype in a Gerstmann–Sträussler–Scheinker P102L family

Acta Neurologica Scandinavica — Sun, 01 Jan 2012 05:00:00 +0100

ConclusionsThis is the first Scandinavian family carrying the P102L mutation in the PRNP gene. Gerstmann–Sträussler–Scheinker syndrome should be considered in the differential diagnosis when handling with patients with ataxia and/or dementia of unclear aetiology. (Source: Acta Neurologica Scandinavica)

Discoveries Could Slow Dysfunction in Spinocerebellar Ataxia Type 1

Clinical Neurology News — Sun, 01 Jan 2012 05:00:00 +0100

Two different approaches to treating spinocerebellar ataxia type 1 – aerobic exercise or delivery of vascular endothelial growth factor – appeared to halt or slow the dysfunction of vulnerable cerebellar and brain stem cells in separate studies of a mouse model that closely mirrors the human disease. (Source: Clinical Neurology News)

Progressive ataxia with palatal tremor due to gluten sensitivity

Movement Disorders — Sun, 01 Jan 2012 05:00:00 +0100

(Source: Movement Disorders)

Celiac disease, wheat allergy, and gluten sensitivity: when gluten free is not a fad.

JPEN Journal Of Parenteral And Enteral Nutrition — Sun, 01 Jan 2012 05:00:00 +0100

Authors: Pietzak M Abstract As the gluten-free diet (GFD) gains in popularity with the general public, health practitioners are beginning to question its real health benefits. For those patients with celiac disease (CD), the GFD is considered medical nutrition therapy, as well as the only proven treatment that results in improvements in symptomatology and small bowel histology. Those with wheat allergy also benefit from the GFD, although these patients often do not need to restrict rye, barley, and oats from their diet. Gluten sensitivity is a controversial subject, where patients who have neither CD nor wheat allergy have varying degrees of symptomatic improvement on the GFD. Conditions in this category include dermatitis herpetiformis (DH), irritable bowel syndrome (IBS), and neu...

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Characterization of glioma stem cells through multiple stem cell markers and their specific sensitization to double strand breaks‐inducing agents by pharmacological inhibition of Ataxia Telangiectasia Mutated protein

Brain Pathology — Sun, 01 Jan 2012 05:00:00 +0100

In conclusion, pharmacological inhibition of ATM may specifically sensitize GSC to DSB‐inducing agents while sparing non‐stem cells. (Source: Brain Pathology)

Serious invasive saffold virus infections in children, 2009.

Emerging Infectious Diseases — Sun, 01 Jan 2012 05:00:00 +0100

Authors: Nielsen AC, Böttiger B, Banner J, Hoffmann T, Nielsen LP Abstract The first human virus in the genus Cardiovirus was described in 2007 and named Saffold virus (SAFV). Cardioviruses can cause severe infections of the myocardium and central nervous system in animals, but SAFV has not yet been convincingly associated with disease in humans. To study a possible association between SAFV and infections in the human central nervous system, we designed a real-time PCR for SAFV and tested cerebrospinal fluid (CSF) samples from children <4 years of age. SAFV was detected in 2 children: in the CSF and a fecal sample from 1 child with monosymptomatic ataxia caused by cerebellitis; and in the CSF, blood, and myocardium of another child who died suddenly with no history of illness. ...

Prevalence and severity of voice and swallowing difficulties in mitochondrial disease.

International Journal of Language and Communication Disorders — Sun, 01 Jan 2012 05:00:00 +0100

Conclusions & Implications: Dysphagia and dysarthria have been identified as symptoms in previous research, however the prevalence and pathophysiology of these symptoms have not been explored. This paper indicates that voice and swallow problems are a common, though predominantly mild feature of mitochondrial disease and that there is a core group of pathophysiological symptoms linked to the presence of voice and swallowing problems. This paper recommends early referral to speech and language therapists to identify emerging dysphonia and dysphagia and to provide appropriate intervention. PMID: 22268906 [PubMed - in process] (Source: International Journal of Language and Communication Disorders)

Differentiating profiles of speech impairments in Friedreich's ataxia: a perceptual and instrumental approach.

International Journal of Language and Communication Disorders — Sun, 01 Jan 2012 05:00:00 +0100

Conclusions & Implications: The distinct profiles of dysarthria associated with FRDA indicate that approaches that address multiple subsystems are necessary for the accurate characterization and quantification of the motor speech disorder. Further research is required to investigate the decline in speech function as the disease progresses, as changes in speech function over time may be a good indicator of neurological decline in FRDA. PMID: 22268902 [PubMed - in process] (Source: International Journal of Language and Communication Disorders)

Lhermitte - duclos disease with syrinx: case report and literature review.

Turkish Neurosurgery — Thu, 29 Dec 2011 18:00:03 +0100

We report an 18-year-old female patient who presented to us with history of headache and gait ataxia and was observed to have Lhermitte-Duclos disease with cervical cord syrinx on imaging. DISCUSSION: To our knowledge this is the fifth case of Lhermitte-Duclos disease with syringomyelia in the pediatric age group. The treatment of this condition is decompression of the lesion. Malignant transformation never occurs and the prognosis is excellent. PMID: 22194132 [PubMed - in process] (Source: Turkish Neurosurgery)

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Ataxia and HIV: Clinicopathologic Correlations in a Case of HIV-Associated Cerebellar Leukoencephalopathy.

Cerebellum — Thu, 29 Dec 2011 05:00:00 +0100

Authors: Ganos C, Bernreuther C, Matschke J, Gerloff C, Münchau A, Leypoldt F PMID: 22205440 [PubMed - as supplied by publisher] (Source: Cerebellum)

Transgenic neuronal overexpression reveals that stringently regulated p23 expression is critical for coordinated movement in mice

Molecular Neurodegeneration — Wed, 28 Dec 2011 05:00:00 +0100

Conclusions: These results demonstrate that proper level of p23 expression is critical for neuronal function, and perturbing p23 function by overexpression initiates a cascade of cellular reactions in brainstem that leads to severe motor deficits and other neurological problems, which culminate in premature death. The neurological phenotype observed in Hup23 mice highlights significant adverse effects associated with manipulating neuronal expression of p23, a previously described negative modulator of gamma-secretase activity and beta-amyloid production. Moreover, our report has broader relevance to molecular mechanisms in several neurodegenerative diseases as it highlights the inherent vulnerability of the early secretory pathway mechanisms that ensure proteostasis in neurons. (Source: Mo...

Association between ATM polymorphisms and cancer risk: a meta-analysis.

Molecular Biology Reports — Wed, 28 Dec 2011 05:00:00 +0100

In conclusion, ATM rs664143 polymorphism was associated with cancer susceptibility. ATM rs664143 polymorphism was significantly associated with lung cancer risk. ATM rs664677 polymorphism was associated with decreased lung cancer risk as well as increased breast cancer risk. PMID: 22203481 [PubMed - as supplied by publisher] (Source: Molecular Biology Reports)

The cerebellar cognitive profile

Brain — Mon, 26 Dec 2011 05:00:00 +0100

The cerebellar role in non-motor functions is supported by the clinical finding that lesions confined to cerebellum produce the cerebellar cognitive affective syndrome. Nevertheless, there is no consensus regarding the overall cerebellar contribution to cognition. Among other reasons, this deficiency might be attributed to the small sample sizes and narrow breadths of existing studies on lesions in cerebellar patients, which have focused primarily on a single cognitive domain. The aim of this study was to examine the expression of cerebellar cognitive affective syndrome with regard to lesion topography in a large group of subjects with cerebellar damage. We retrospectively analysed charts from patients in the Ataxia Lab of Santa Lucia Foundation between 1997 and 2007. Of 223 charts, 156 we...

Triplet repeat RNA structure and its role as pathogenic agent and therapeutic target

Nucleic Acids Research — Sun, 25 Dec 2011 05:00:00 +0100

We describe various concepts and approaches aimed at the selective inhibition of mutant transcript activity in experimental therapies developed for repeat-associated diseases. (Source: Nucleic Acids Research)

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NF-{kappa}B regulates DNA double-strand break repair in conjunction with BRCA1-CtIP complexes

Nucleic Acids Research — Sun, 25 Dec 2011 05:00:00 +0100

NF-B is involved in immune responses, inflammation, oncogenesis, cell proliferation and apoptosis. Even though NF-B can be activated by DNA damage via Ataxia telangiectasia-mutated (ATM) signalling, little was known about an involvement in DNA repair. In this work, we dissected distinct DNA double-strand break (DSB) repair mechanisms revealing a stimulatory role of NF-B in homologous recombination (HR). This effect was independent of chromatin context, cell cycle distribution or cross-talk with p53. It was not mediated by the transcriptional NF-B targets Bcl2, BAX or Ku70, known for their dual roles in apoptosis and DSB repair. A contribution by Bcl-xL was abrogated when caspases were inhibited. Notably, HR induction by NF-B required the targets ATM and BRCA2. Additionally, we provide evid...

Pathoanatomy of Cerebellar Degeneration in Spinocerebellar Ataxia Type 2 (SCA2) and Type 3 (SCA3).

Cerebellum — Sat, 24 Dec 2011 05:00:00 +0100

This study demonstrates that the cerebellar Purkinje cell layer and all four deep cerebellar nuclei consistently undergo considerable neuronal loss in SCA2 and SCA3. These cerebellar findings contribute substantially to the pathogenesis of clinical symptoms (i.e., dysarthria, intention tremor, oculomotor dysfunctions) of SCA2 and SCA3 patients and may facilitate the identification of the initial pathological alterations of the pathological processes of SCA2 and SCA3 and reconstruction of its spread through the brain. PMID: 22198871 [PubMed - as supplied by publisher] (Source: Cerebellum)

[Acute disseminated encephalomyelitis associated with herpes virus infection: A case report.]

Archives de Pediatrie — Sat, 24 Dec 2011 05:00:00 +0100

We report a case of ADEM in a 4-year-old girl, who was diagnosed based on the data from a brain MRI, which revealed multiple demyelinization foci in the periventricular white matter, the semi-oval centers, and the thalamic regions, both bilaterally and symmetrically. The clinical course was characterized by complete recovery 10 days after steroid therapy. In the literature, more than the half of the patients treated for ADEM had a good prognosis, with recovery and no sequelae. Clinical improvement is generally noted in the hours or days following the initiation of treatment. However, in the most severe cases of ADEM, the most frequent neurological sequelae consist in focal deficiencies of the limbs and ataxia or visual disorders. Cognitive and behavioral disorders are noted in 6 to 50% of ...

Lack of ATM induces structural and functional changes in the heart: Role in β‐adrenergic receptor‐stimulated apoptosis

Experimental Physiology — Wed, 21 Dec 2011 05:00:00 +0100

Abstract Ataxia telangiectasia mutated kinase (ATM) is involved in cell cycle checkpoints, DNA repair and apoptosis. β‐adrenergic receptor (β‐AR) stimulation induces cardiac myocyte apoptosis. Here we analyzed basal myocardial structure and function in ATM knockout (KO) mice, and tested the hypothesis that ATM modulates β‐AR‐stimulated myocyte apoptosis. Left ventricular (LV) structure and function, myocyte apoptosis, fibrosis and expression of fibrosis‐, hypertrophy‐ and apoptosis‐related proteins were examined in wild‐type (WT) and KO mice with or without L‐isoproterenol treatment for 24h. Body and heart weights were lower in KO mice. M‐mode echocardiography showed reduced septal wall thicknesses and LV diameters in KO mice. Doppler echocardiography showed incre...

Apogeotropic central positional nystagmus as a sole sign of nodular infarction

Neurological Sciences — Tue, 20 Dec 2011 16:45:56 +0100

We present a patient with nodular infarction who had positional vertigo with nystagmus as a sole manifestation. Video-oculography showed apogeotropic positional horizontal nystagmus during head turning while supine, which was consistent with apogeotropic BPPV involving the horizontal canal. MRI disclosed acute infarct in the nodulus. Nodulus infarction should be considered in a patient with positional nystagmus, especially when the presenting symptoms and signs are consistent with BPPV involving the horizontal canal. Content Type Journal ArticleCategory Case ReportPages 1-3DOI 10.1007/s10072-011-0884-xAuthors Hyun-Ah Kim, Department of Neurology, Keimyung University School of Medicine, 194 Dongsan dong, Daegu, 700-712 South KoreaHyon-Ah Yi, Department of Neurology, Keimyung Univ...

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Phase Ib trial of radiotherapy in combination with combretastatin-A4-phosphate in patients with non-small-cell lung cancer, prostate adenocarcinoma, and squamous cell carcinoma of the head and neck

Annals of Oncology — Tue, 20 Dec 2011 05:00:00 +0100

Conclusions: Radiotherapy with CA4P appears well tolerated in most patients. The combination of CA4P, cetuximab, and radiotherapy needs further scrutiny before it can be recommended for clinical studies. (Source: Annals of Oncology)

The ToxTracker Assay: Novel GFP Reporter Systems that Provide Mechanistic Insight into the Genotoxic Properties of Chemicals

Toxicological Sciences — Tue, 20 Dec 2011 05:00:00 +0100

People are exposed to an ever-increasing number of chemical compounds that are developed by industry for a wide range of applications. These compounds may harmfully react with different cellular components and activate specific defense mechanisms that provide protection against the toxic, mutagenic, and possibly oncogenic consequences of exposure. Monitoring the activation of specific cellular signaling pathways upon exposure may therefore allow reliable and mechanism-based assessment of potential (geno)toxic properties of chemicals, while providing insight into their primary mode of toxicity. By whole-genome transcription profiling of mouse embryonic stem cells, we identified genes that were transcriptionally activated upon exposure to either genotoxic compounds or pro-oxidants. For selec...

Ataxia telangiectasia mutated (ATM) modulates long interspersed element-1 (L1) retrotransposition in human neural stem cells [Neuroscience]

Proceedings of the National Academy of Sciences — Tue, 20 Dec 2011 05:00:00 +0100

Long interspersed element-1 (L1) retrotransposons compose ∼20% of the mammalian genome, and ongoing L1 retrotransposition events can impact genetic diversity by various mechanisms. Previous studies have demonstrated that endogenous L1 retrotransposition can occur in the germ line and during early embryonic development. In addition, recent data indicate that engineered human L1s can undergo somatic retrotransposition in human neural progenitor cells and that an increase in human-specific L1 DNA content can be detected in the brains of normal controls, as well as in Rett syndrome patients. Here, we demonstrate an increase in the retrotransposition efficiency of engineered human L1s in cells that lack or contain severely reduced levels of ataxia telangiectasia mutated, a serine/threonine ki...

Reduction and Fixation of Cranial Cervical Fracture/Luxations using Screws and Polymethylmethacrylate (PMMA) Cement: A Distraction Technique Applied to the Base of the Skull in Thirteen Dogs

Veterinary Surgery — Tue, 20 Dec 2011 05:00:00 +0100

ConclusionsThis surgical distraction technique was a reliable, relatively simple method to obtain reduction of fracture/luxations of C1‐2 to re‐align the spinal canal. Mortality in this series appears lower than that previously reported and supports surgical management of these injuries. (Source: Veterinary Surgery)

Genetics Home Reference: PRICKLE1-related progressive myoclonus epilepsy with ataxia

NLM General Announcements — Fri, 16 Dec 2011 20:30:12 +0100

(Source: NLM General Announcements)

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Obatoclax Plus Fludarabine/Rituximab Is Well Tolerated and Active in Patients With Relapsed CLL/SLL

Clinical Care Options Oncology - Leukemia — Fri, 16 Dec 2011 15:57:05 +0100

Capsule Summary - In this phase I trial involving 13 patients, the most frequent adverse events with obatoclax plus fludarabine and rituximab were grade 1-2 euphoria, dizziness, and ataxia and grade 3 or higher neutropenia. (Source: Clinical Care Options Oncology - Leukemia)

Ionizing radiation induced signaling of DNA damage response molecules in RAW 264.7 and CD4(+) T cells.

Molecular and Cellular Biochemistry — Fri, 16 Dec 2011 05:00:00 +0100

Authors: Dhariwala FA, Narang H, Krishna M Abstract Ionizing radiation (IR) treatment results in activation of several DNA damage response molecules, such as ataxia telangiectasia, mutated (ATM), and DNA-dependent protein kinase (DNAPK) in mammals that are increasingly recognized for their potential roles in the sensing of DNA damage and initiating the subsequent protein kinase cascade. In vitro evidence indicates that both ATM and DNA-PK are responsible for efficient repair of DNA double strand breaks in response to IR exposure. To unravel the role of ATM and DNA-PK, we studied the mRNA and protein levels of ATM, DNA-PK and their downstream substrates in two different cell types after irradiation viz. macrophage like RAW264.7 cells and CD4(+) T cells isolated from mice spleen. Our...

Development of a romifidine constant rate infusion with or without butorphanol for standing sedation of horses

Veterinary Anaesthesia and Analgesia — Wed, 14 Dec 2011 17:32:34 +0100

Conclusion Romifidine bolus, followed by CRI, provided constant sedation assessed by HHAG. Butorphanol was ineffective in reducing romifidine requirements in unstimulated horses, but prolonged the sedation caused by the initial romifidine bolus.Clinical relevance Both protocols need to be tested under clinical conditions. (Source: Veterinary Anaesthesia and Analgesia)

Multispectral imaging flow cytometry reveals distinct frequencies of γ‐H2AX foci induction in DNA double strand break repair defective human cell lines

Cytometry Part A — Tue, 13 Dec 2011 05:00:00 +0100

In this study, we have employed the novel technique of multispectral imaging flow cytometry to compare the induction and repair of γ‐H2AX foci in three human cell types with different capacities for the repair of DNA double strand breaks (DSB). A repair normal fibroblast cell line MRC5‐SV1, a DSB repair defective ataxia telangiectasia (AT5BIVA) cell line, and a DNA‐PKcs deficient cell line XP14BRneo17 were exposed to 2 Gy gamma radiation from a 60Cobalt source. Thirty minutes following exposure, we observed a dramatic induction of foci in the nuclei of these cells. After 24 hrs, there was a predictable reduction on the number of foci in the MRC5‐SV1 cells, consistent with the repair of DNA DSB. In the AT5BIVA cells, persistence of the foci over a 24‐hr period was due to the fail...

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Neonatal seizures associated with a severe neonatal myoclonus like dyskinesia due to a familial KCNQ2 gene mutation.

European Journal of Paediatric Neurology — Tue, 13 Dec 2011 05:00:00 +0100

CONCLUSION: KCNQ2 mutations can present with a neonatal onset multifocal myoclonus-like dyskinesia. PMID: 22169383 [PubMed - as supplied by publisher] (Source: European Journal of Paediatric Neurology)

Use of Acetazolamide in Sulfonamide-Allergic Patients With Neurologic Channelopathies [Observation]

Archives of Neurology — Mon, 12 Dec 2011 05:00:00 +0100

Conclusions These 3 cases confirm that the carbonic anhydrase inhibitor acetazolamide can be given to patients with a history of allergic skin rash with antibiotic sulfonamide. (Source: Archives of Neurology)

The APOE {varepsilon}2 Allele Increases the Risk of Earlier Age at Onset in Machado-Joseph Disease [Original Contribution]

Archives of Neurology — Mon, 12 Dec 2011 05:00:00 +0100

Conclusion The polymorphism at the APOE gene plays a role as a genetic modifier of MJD phenotype. (Source: Archives of Neurology)

The cerebellar cognitive profile

Brain — Sun, 11 Dec 2011 05:00:00 +0100

Fragile X–Associated tremor ataxia syndrome in FMR1 gray zone allele carriers

Movement Disorders — Sun, 11 Dec 2011 05:00:00 +0100

Conclusions:Our cases suggest that the definition of the FXTAS may need to be broadened to include individuals with FMR1 repeat expansions in the gray zone. These neurological signs may be due to elevated levels of expanded CGG repeat FMR1 mRNA in the gray zone carriers, similar to the changes seen in premutation carriers with FXTAS. © 2011 Movement Disorder Society (Source: Movement Disorders)

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Sorting out childhood ataxias

The Journal of Pediatrics — Sat, 10 Dec 2011 19:07:32 +0100

Ataxia is a somewhat unusual complaint in children, and the differential diagnosis is daunting. From the standpoint of the primary care pediatrician, however, perhaps the most important initial classification is the differentiation between genetic and acquired causes. Within each of these categories, there are a host of possible diagnoses. (Source: The Journal of Pediatrics)

Substantia nigra hypoechogenicity in friedreich ataxia

Movement Disorders — Fri, 09 Dec 2011 05:00:00 +0100

(Source: Movement Disorders)

Mammosphere cells from high-passage MCF7 cell line show variable loss of tumorigenicity and radioresistance

Cancer Letters — Fri, 09 Dec 2011 05:00:00 +0100

In this study, we report that mammospheres derived from MCF-7 sublines after different passage numbers were consistently enriched for CD44+/CD24−/low cells but were not consistently enriched for tumorigenic and radioresistant cells. The tumorigenicity and radioresistance of MSs were associated with their sphere-forming ability, proliferation ability in vitro, and intracellular reactive oxygen species (ROS) levels. The radioresistant MSs showed significant cell cycle arrest in G2/M phase after X-ray irradiation and expressed higher ataxia telangiectasia mutated (ATM) mRNA levels. These results suggest that MSs from high-passage cancer cell lines were not consistently enriched for stem-like cancer cells with higher tumorigenicity and enhanced radioresistance. (Source: Cancer Letters)

Bilateral achilles tendon enlargement.

Orthopedics — Thu, 08 Dec 2011 22:48:02 +0100

Authors: Huang L, Miao XD, Yang DS, Tao HM Abstract Cerebrotendinous xanthomatosis is a rare, autosomal-recessive, lipid-storage disease with accumulation of cholestanol in most tissues, particularly within the Achilles tendons. It has been characterized both clinically and biochemically, and recently from the molecular biological aspect as well. Juvenile cataract, childhood diarrhea, mental retardation, cerebellar ataxia, and tendon xanthomas are the most prominent features of this disease. Bilateral symmetrical firm masses of Achilles tendons may be the first symptom the patient recognizes because it can jeopardize his or her ability to walk. However, the treatment strategies for tendon tumors vary.In a recent case, we diagnosed the disease properly, according to the clinical man...

Phase I study of the safety, tolerability and pharmacokinetics of PHA-848125AC, a dual tropomyosin receptor kinase A and cyclin-dependent kinase inhibitor, in patients with advanced solid malignancies

Investigational New Drugs — Thu, 08 Dec 2011 18:11:27 +0100

Conclusion The RP2D of PHA-848125AC was 150 mg/day on both schedules. Based on the responses noted in thymic carcinoma, a phase II study for patients with that disease is currently enrolling. Content Type Journal ArticleCategory PHASE I STUDIESPages 1-10DOI 10.1007/s10637-011-9774-6Authors Glen J. Weiss, Virginia G. Piper Cancer Center at Scottsdale Healthcare (VGPCC), 10510 N 92nd St, Ste 200, Scottsdale, AZ 85258, USAManuel Hidalgo, Johns Hopkins, Baltimore, MD, USAMitesh J. Borad, Virginia G. Piper Cancer Center at Scottsdale Healthcare (VGPCC), 10510 N 92nd St, Ste 200, Scottsdale, AZ 85258, USADaniel Laheru, Johns Hopkins, Baltimore, MD, USARaoul Tibes, Virginia G. Piper Cancer Center at Scottsdale Healthcare (VGPCC), 10510 N 92nd St, Ste 200, Scottsdale, AZ 85258, USARam...

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Devastating 'Founder Effect' Genetic Disorder Raced To Defective Mitochondria In Cerebellar Neurons

Health News from Medical News Today — Thu, 08 Dec 2011 08:00:00 +0100

Defective mitochondria, the energy-producing powerhouses of the cell, trigger an inherited neurodegenerative disorder that first shows itself in toddlers just as they are beginning to walk, Canadian scientists reported at the American Society for Cell Biology Annual Meeting in Denver. The disorder, Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS), was first identified in the late 1970s among the descendants of a small population of 17th century French immigrants who settled in the Charlevoix and the Saguenay River regions northeast of Quebec City... (Source: Health News from Medical News Today)

The yeast metacaspase is implicated in oxidative stress response in frataxin-deficient cells

FEBS Letters — Wed, 07 Dec 2011 05:00:00 +0100

Highlights: ► Sensitivity of yeast frataxin-deficient cells to hydrogen peroxide is partially mediated by metacaspase. ► In the absence of metacaspase, frataxin-deficient cells recover antioxidant capacity and heme biosynthesis. ► Metacaspase is implicated in mitochondrial energy metabolism and intracellular redox control.Abstract: Friedreich ataxia is the most common recessive neurodegenerative disease and is caused by reduced expression of mitochondrial frataxin. Frataxin depletion causes impairment in iron–sulfur cluster and heme biosynthesis, disruption of iron homeostasis and hypersensitivity to oxidants. Currently no pharmacological treatment blocks disease progression, although antioxidant therapies proved to benefit patients. We show that sensitivity of yeast frataxin-defic...

Severe reaction to radiotherapy for breast cancer as the presenting feature of ataxia telangiectasia

British Journal of Cancer AOP — Tue, 06 Dec 2011 05:00:00 +0100

Authors: P J Byrd, V Srinivasan, J I Last, A Smith, P Biggs, E F Carney, A Exley, C Abson, G S Stewart, L Izatt & A M Taylor (Source: British Journal of Cancer AOP)

PTEN regulates synaptic plasticity independently of its effect on neuronal morphology and migration.

The Journal of Physiology — Tue, 06 Dec 2011 05:00:00 +0100

Authors: Sperow M, Berry RB, Bayazitov IT, Zhu G, Baker SJ, Zakharenko SS Abstract The tumor suppressor phosphatase and tensin homolog (PTEN) is the central negative regulator of the phosphatidylinositol 3-kinase (PI3K)- signaling pathway, which mediates diverse processes in various tissues. In the nervous system, the PI3K pathway modulates proliferation, migration, cellular size, synaptic transmission, and plasticity. Neurologic abnormalities such as autism, seizures, and ataxia are associated with inherited PTEN mutations. PTEN loss during early development is associated with extensive deficits in neuronal migration and substantial hypertrophy of neurons and synaptic densities; however, whether its effect on synaptic transmission and plasticity is direct or mediated by structural...

Prevalence Rate and Functional Status of Cerebellar Ataxia in Korea.

Cerebellum — Tue, 06 Dec 2011 05:00:00 +0100

Authors: Joo BE, Lee CN, Park KW Abstract Cerebellar ataxia (hereinafter referred to as CA) designate a group of neurodegenerative disorders. CA is distinguished into a group of hereditary and non-hereditary disorders. CA shows clinically progressive features and accompanies various neurological abnormalities. However, there are very few studies and case reports in Korean patients. To estimate the prevalence rate and current status of the CA patients in Korea, we used data from the Health Insurance Review and Assessment Service (HIRAS) and from the National Health Insurance Corporation. To evaluate the functional status of CA patient in Korea, we conducted a simple random sampling among the 500 members of Korea Ataxia Society registered on its homepage. We evaluated the functional ...

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Oncogenic stress sensitizes murine cancers to hypomorphic suppression of ATR

Journal of Clinical Investigation — Fri, 02 Dec 2011 08:01:27 +0100

Oncogenic Ras and p53 loss-of-function mutations are common in many advanced sporadic malignancies and together predict a limited responsiveness to conventional chemotherapy. Notably, studies in cultured cells have indicated that each of these genetic alterations creates a selective sensitivity to ataxia telangiectasia and Rad3-related (ATR) pathway inhibition. Here, we describe a genetic system to conditionally reduce ATR expression to 10% of normal levels in adult mice to compare the impact of this suppression on normal tissues and cancers in vivo. Hypomorphic suppression of ATR minimally affected normal bone marrow and intestinal homeostasis, indicating that this level of ATR expression was sufficient for highly proliferative adult tissues. In contrast, hypomorphic ATR reduction potentl...

Cytosolic DNA Triggers Mitochondrial Apoptosis via DNA Damage Signaling Proteins Independently of AIM2 and RNA Polymerase III.

Journal of Immunology — Fri, 02 Dec 2011 05:00:00 +0100

Authors: Wenzel M, Wunderlich M, Besch R, Poeck H, Willms S, Schwantes A, Kremer M, Sutter G, Endres S, Schmidt A, Rothenfusser S Abstract A key host response to limit microbial spread is the induction of cell death when foreign nucleic acids are sensed within infected cells. In mouse macrophages, transfected DNA or infection with modified vaccinia virus Ankara (MVA) can trigger cell death via the absent in melanoma 2 (AIM2) inflammasome. In this article, we show that nonmyeloid human cell types lacking a functional AIM2 inflammasome still die in response to cytosolic delivery of different DNAs or infection with MVA. This cell death induced by foreign DNA is independent of caspase-8 and carries features of mitochondrial apoptosis: dependence on BAX, APAF-1, and caspase-9. Although ...

[Ophthalmoplegia with bilateral mydriasis.]

Der Ophthalmologe — Fri, 02 Dec 2011 05:00:00 +0100

We report the case history of a 41-year-old patient who, following bronchial infection, presented with progressive ophthalmoplegia in both eyes, dilated pupils unresponsive to light or convergence and ataxia. The suspected diagnosis of Miller-Fisher syndrome was confirmed by the detection of anti-ganglioside GQ1b antibodies. PMID: 22130723 [PubMed - as supplied by publisher] (Source: Der Ophthalmologe)

Monoclonal Gammopathy of Undetermined Significance (MGUS) in a Man with Fragile X-associated Tremor/Ataxia Syndrome

Infectious Diseases in Obstetrics and Gynecology — Thu, 01 Dec 2011 16:31:38 +0100

We report the clinical presentation and laboratory findings of a 69-year-old man with fragile X-associated tremor ataxia syndrome (FXTAS), a progressive neurodegenerative disorder, who was noted to have monoclonal gammopathy of undetermined significance (MGUS), a plasma cell proliferative disorder and a precursor disease of multiple myeloma. Both MGUS and FXTAS are associated with microRNA (miRNA) dysregulation. We speculate that individuals with FXTAS may be predisposed to MGUS and further studies are warranted regarding this association. (Source: Infectious Diseases in Obstetrics and Gynecology)

Aspirin: Ataxia in an infant following accidental poisoning: case report

Reactions — Thu, 01 Dec 2011 07:29:01 +0100

(Source: Reactions)

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Long-term observation of absence of REM sleep caused by pontine cavernous hemangioma

Sleep Medicine — Thu, 01 Dec 2011 05:00:00 +0100

We report here on a 17-year-old girl in whom no rapid eye movement (REM) sleep has been detected for three years due to pontine cavernous hemangioma (A). She manifested truncal ataxia, facial nerve palsy, and disturbance in ocular motility. Polysomnography (PSG) revealed obstructive sleep apneas (OSA) (apnea/hypopnea index; AHI: 15.4/h) with significant snoring and central apnea (central AHI: 6.7/h) but without any periods of REM sleep (B). PSG was repeated four times in the next two years and eight months and none of the recording demonstrated typical epochs of REM sleep in spite of successful treatment for OSA by non-invasive positive pressure ventilation. No REMs were detected, although her spontaneous eye movements were documented in wakefulness. There were abundant muscle twitches not...

Evaluation of thoracic epidural analgesia induced by lidocaine, ketamine, or both administered via a lumbosacral approach in dogs.

American Journal of Veterinary Research — Thu, 01 Dec 2011 05:00:00 +0100

Conclusions and Clinical Relevance-Thoracic epidural administration of lidocaine plus ketamine resulted in longer duration of analgesia of the thorax and forelimbs bilaterally in conscious dogs, compared with administration of ketamine or lidocaine alone. Additional studies are needed to determine whether this technique adequately relieves postoperative pain after thoracic surgical procedures and whether it causes respiratory depression in dogs. PMID: 22126684 [PubMed - in process] (Source: American Journal of Veterinary Research)

Incidental findings of mass lesions on neuroimages in children.

Neurosurgical Focus — Thu, 01 Dec 2011 05:00:00 +0100

Authors: Perret C, Boltshauser E, Scheer I, Kellenberger CJ, Grotzer MA Abstract Increasing use of neuroimaging in children has led to more incidental findings of CNS mass lesions, the management of which is uncertain. The authors' aims in this study are to describe these mass lesions and their evolution, as well as to discuss the management options and determine the prevalence of incidental CNS mass lesions at their pediatric clinic. A retrospective study was undertaken in children with primary CNS tumors who were younger than 18 years old and were admitted to the University Children's Hospital of Zurich, Switzerland, between January 1995 and December 2010. In 19 (5.7%) of 335 patients with newly diagnosed CNS tumors, the diagnosis of a CNS mass lesion was an incidental finding. R...

Association of laterality and size of perfusion lesions on neurological deficit in acute supratentorial stroke

International Journal of Stroke — Thu, 01 Dec 2011 05:00:00 +0100

ConclusionsLarger perfusion defects contribute to higher scores on the total and most individual items of the National Institutes of Health Stroke Scale. However, lesion laterality contributes substantially to half the item scores, with greater association of left than right‐brain side. These findings indicate that imaging‐deficit correlations will be improved by designating lesions into an atlas, taking into account side in addition to size. (Source: International Journal of Stroke)

Transient improvement of acquired hepatocerebral degeneration with parkinsonian symptoms after failed liver transplant: case report and literature review.

Thu, 01 Dec 2011 05:00:00 +0100

Conclusions: Our experience demonstrates that orthotopic liver transplant may lead to resolution of acquired hepatocerebral degeneration; however, acquired hepatocerebral degeneration may return with recurrent liver disease. Future studies with long-term follow-up are needed. PMID: 22142042 [PubMed - in process] (Source: Experimental and Clinical Transplantation : official journal of the Middle East Society for Organ Transplantation)

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Propylene glycol intoxication in a dog

Journal of Veterinary Emergency and Critical Care — Thu, 01 Dec 2011 05:00:00 +0100

AbstractObjectiveTo describe the clinical course, treatment, and outcome of a dog with propylene glycol intoxication.Case SummaryAn adult castrated male Australian cattle dog presented to an emergency clinic for an acute onset of ataxia and disorientation after roaming a construction site unsupervised. He tested positive for ethylene glycol using a point‐of‐care test kit. Treatment for ethylene glycol intoxication included intermittent intravenous boluses of 20% ethanol and hemodialysis. Predialysis and postdialysis blood samples were submitted to the toxicology lab to assess for both ethylene and propylene glycol. The patient tested negative for ethylene glycol and positive for propylene glycol at 1100 mg/dL predialysis and 23 mg/dL postdialysis. The dog made a full recovery.New or Un...

Inhibition of poly(ADP‐ribose) polymerase (PARP) and ataxia telangiectasia mutated (ATM) on the chemosensitivity of mantle cell lymphoma to agents that induce DNA strand breaks

Hematological Oncology — Thu, 01 Dec 2011 05:00:00 +0100

AbstractThere is a high incidence of genomic aberration of ataxia telangiectasia mutated (ATM) and genes encoding proteins involved in the ATM pathway in mantle cell lymphoma (MCL). It has been shown that poly(ADP‐ribose) polymerase inhibitor (PARPi) strongly enhances the cytotoxicity of agents, causing single‐strand DNA breaks in cells with impaired homologous recombination repair. Here, we show that PARPi AG14361 potentiates the cytotoxicity induced by topotecan treatment in MCL cell lines, which was not dependent on either TP53 or CHEK2 status. Inhibition and/or knockdown of ATM and BRCA2 did not potentiate the cytotoxic effect of treatment with PARPi and topotecan. With loss of function of ATM, other kinases can still mediate activation of ATM substrates as demonstrated by continue...

How best to address these common movement disorders.

The Journal of Family Practice — Thu, 01 Dec 2011 05:00:00 +0100

Authors: Yaman A, Akdeniz M, Yaman H Abstract This review describes how to manage everything from Parkinson's disease and tic disorders to restless legs syndrome and ataxia. PMID: 22163354 [PubMed - in process] (Source: The Journal of Family Practice)

New-onset psychosis in a patient with spinocerebellar ataxia type 10.

The American Journal of Psychiatry — Thu, 01 Dec 2011 05:00:00 +0100

Authors: Wexler E, Fogel BL PMID: 22193677 [PubMed - in process] (Source: The American Journal of Psychiatry)

Long‐term strategies for the treatment of Refsum's disease using therapeutic apheresis

Journal of Clinical Apheresis — Thu, 01 Dec 2011 05:00:00 +0100

We report on the long‐term lipid apheresis treatment of four patients with severe Refsum's disease. Retinitis pigmentosa, peripheral polyneuropathy, cerebellar ataxia, anosmia, and sensorineural hearing loss were major symptoms exhibiting a progressive course. Lipid apheresis was performed for 5–13 years without severe complications. Maximum levels of phytanic acid before commencing chronic lipid apheresis were >300 mg/l. During steady state with lipid apheresis, mean phytanic acid before treatments was 87 mg/l and was reduced to 36 mg/l. Mean reduction rate was 59% per treatment. In all patients, abnormal motor nerve conduction velocity with signs of chronic denervation improved, morphological and functional stabilization of eye involvement was observed. Lipid apheresis prevented t...

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ATM Gene and Risk of Breast CancerATM Gene and Risk of Breast Cancer

Medscape Today Headlines — Tue, 29 Nov 2011 11:50:23 +0100

Can the ataxia-telangiectasia mutated (ATM) gene provide useful information on breast cancer risk, or is it just too rare? Breast Cancer Research (Source: Medscape Today Headlines)

The role of the central flexible region on the aggregation and conformational properties of human ataxin‐3

FEBS Journal — Tue, 29 Nov 2011 05:00:00 +0100

SummaryAggregation of human ataxin‐3 (AT3) into amyloid fibrils is responsible for the spinocerebellar ataxia type 3. This protein consists of a folded N‐terminal domain (Josephin domain, residues 1‐182), a central flexible region (residues 183‐291), a poly‐glutamine (polyQ) sequence of variable length, and a short C‐terminal flexible region. Very little is known on the influence of the central flexible region on the conformational and aggregation properties of this protein. The goal of this work was to investigate the specific role of this portion of the protein (residues 183‐291). To this purpose, the protein fragments 1‐182 (AT3/182) and 1‐291 (AT3/291) have been produced and compared by Thioflavin‐T (ThT) fluorescence, Fourier transform infrared (FTIR) spectroscopy,...

DNA-damage accumulation and replicative arrest in Hutchinson-Gilford progeria syndrome.

Biochemical Society Transactions — Tue, 29 Nov 2011 04:28:23 +0100

Authors: Musich PR, Zou Y Abstract A common feature of progeria syndromes is a premature aging phenotype and an enhanced accumulation of DNA damage arising from a compromised repair system. HGPS (Hutchinson-Gilford progeria syndrome) is a severe form of progeria in which patients accumulate progerin, a mutant lamin A protein derived from a splicing variant of the lamin A/C gene (LMNA). Progerin causes chromatin perturbations which result in the formation of DSBs (double-strand breaks) and abnormal DDR (DNA-damage response). In the present article, we review recent findings which resolve some mechanistic details of how progerin may disrupt DDR pathways in HGPS cells. We propose that progerin accumulation results in disruption of functions of some replication and repair factors, caus...

Amelioration of caudal thoracic syringohydromyelia following surgical management of an adjacent arachnoid cyst

The Journal of Small Animal Practice — Mon, 28 Nov 2011 05:00:00 +0100

A nine‐year‐old male, neutered, pug was presented for investigation of progressive ambulatory paraparesis and pelvic limb ataxia of three months' duration. Magnetic resonance imaging was suggestive of caudal thoracic syringohydromyelia with an adjacent intradural arachnoid cyst. The cyst was marsupialised following dorsal laminectomy. Neurological status had improved 10 weeks following surgery when repeat magnetic resonance imaging revealed reduced spinal cord compression both as a result of resolution of the cyst and reduction in size of the syringohydromyelia. At 17 months following surgery, the dog showed further improvements in neurological status, exhibiting mild pelvic limb ataxia and proprioceptive deficits. Improved cerebrospinal fluid flow following surgery may have played a r...

Vincristine‐induced central neurotoxicity in a collie homozygous for the ABCB1Δ mutation

The Journal of Small Animal Practice — Mon, 28 Nov 2011 05:00:00 +0100

A six‐year‐old, neutered, female collie was presented to an oncology specialty service after developing tetraparesis and self‐mutilation that progressively worsened while receiving chemotherapy for lymphoma. Neurologic examination revealed ataxia, paresis and diminished conscious proprioception in all limbs with entire spinal reflexes. Magnetic resonance imaging of the brain and spinal cord was normal. Electromyography of the limbs ruled out a vincristine‐induced peripheral neuropathy. Cerebrospinal fluid analysis and cerebrospinal fluid and serum testing for Neospora and Toxoplasma were normal. Results of MDR1 genotyping revealed that the dog was homozygous for the ABCB1‐1Δ (MDR1) mutation. This clinical presentation strongly resembled the effects seen from inadvertent intrathe...

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Gesundheit! Sneezing, paraesthesiae and ataxia in a 35-year-old man.

Practical Neurology — Sat, 26 Nov 2011 13:13:44 +0100

Authors: Stokes V, Küker W, Schulz UG PMID: 22100948 [PubMed - in process] (Source: Practical Neurology)

Basic Research on Cerebellar Gene Therapy Using Lentiviral Vectors.

Brain Research — Sat, 26 Nov 2011 05:00:00 +0100

Authors: Hirai H Abstract Postmitotic neurons are resistant to gene delivery. However, lentiviral vectors allow the introduction of a foreign gene efficiently into neurons without significant toxicity to the infected cells (Sawada et al., Cerebellum 9(3):291-302, 2010). In addition, these vectors show a high tropism for neurons, and the transgenes they carry have been shown to be continuously expressed for at least a couple of years (Hirai, Cerebellum 7(3):273-8, 2008). We developed a method to express a foreign gene efficiently in cerebellar Purkinje cells in vivo (Takayama et al., Neurosci Lett 443(1):7-11, 2008; Torashima et al., Brain Res 1082(1):11-22, 2006, The Eur J Neurosci 24(2):371-80, 2006). Using our method, various experiments were carried out to study the pathophysiol...

Heterogeneity of Marinesco-Sjögren Syndrome: Report of Two Cases

Pediatric Neurology — Fri, 25 Nov 2011 13:48:58 +0100

We describe two Turkish patients with clinical characteristics of Marinesco-Sjögren syndrome, but without mutations in SIL1. These two patients also manifested cerebral white matter involvement in cranial imaging, which was previously described in Marinesco-Sjögren syndrome. Marinesco-Sjögren syndrome is genetically heterogeneous, and mutations of SIL1 are often not evident. Consequently, we presume that new genes for Marinesco-Sjögren syndrome await discovery. New genes hold the promise of furthering the mechanistic understanding of the condition, enabling clinically meaningful genetic classification schemes to be designed. (Source: Pediatric Neurology)

Hashimoto’s Encephalopathy in Children and Adolescents

Pediatric Neurology — Fri, 25 Nov 2011 13:48:58 +0100

We describe the clinical and laboratory findings of four children (aged 9-15 years) with Hashimoto’s encephalopathy. The clinical features of two patients at presentation included epileptic seizures and confusion. The other presenting signs included breath-holding spells, behavioral problems, psychosis, and ataxia (one patient each). During their presentation, three patients were euthyroid, and one was hyperthyroid. All patients manifested increased antithyroid antibodies, and all improved with steroid treatment. Hashimoto’s encephalopathy is rarely suspected at presentation. Therefore, greater awareness of its signs by clinicians is necessary for proper diagnoses. (Source: Pediatric Neurology)

FXN methylation predicts expression and clinical outcome in friedreich ataxia

Annals of Neurology — Fri, 25 Nov 2011 05:00:00 +0100

AbstractObjective:Friedreich ataxia (FRDA) is the most common ataxia and results from an expanded GAA repeat in the first intron of FXN. This leads to epigenetic modifications and reduced frataxin. We investigated the relationships between genetic, epigenetic and clinical parameters in a large case‐control study of FRDA.Methods:Clinical data and samples were obtained from individuals with FRDA during annual visits to our dedicated FRDA clinic. GAA expansions were evaluated by PCR and restriction endonuclease digest. DNA methylation was measured using bisulfite‐based EpiTYPER MassARRAY (Sequenom). FXN expression was determined using real‐time RT‐PCR. Significant correlations between the different parameters were examined using the non‐parametric Spearman's rank correlation coeffic...

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Cerebellar Stimulation in Ataxia.

Cerebellum — Fri, 25 Nov 2011 05:00:00 +0100

Authors: Groiss SJ, Ugawa Y Abstract The cerebellum plays an important role in movement execution and motor control by modulation of the primary motor cortex (M1) through cerebello-thalamo-cortical connections. Transcranial magnetic stimulation (TMS) allows direct investigations of neural networks by stimulating neural structures in humans noninvasively. The motor evoked potential to single-pulse TMS of M1 is used to measure the motor cortical excitability. A conditioning stimulus over the cerebellum preceding a test stimulus of the contralateral M1 enables us to study the cerebellar regulatory functions on M1. In this brief review, we describe this cerebellar stimulation method and its usefulness as a diagnostic tool in clinical neurophysiology. PMID: 22116658 [PubMed - as sup...

Effect of Long-Term Climbing Training on Cerebellar Ataxia: A Case Series

Clinical and Developmental Immunology — Thu, 24 Nov 2011 23:55:40 +0100

Conclusion. Climbing training has the potential to serve as a new rehabilitation method for patients with upper and lower limb ataxia. (Source: Clinical and Developmental Immunology)

Phosphorylation of polynucleotide kinase/ phosphatase by DNA-dependent protein kinase and ataxia-telangiectasia mutated regulates its association with sites of DNA damage

Nucleic Acids Research — Wed, 23 Nov 2011 05:00:00 +0100

Human polynucleotide kinase/phosphatase (PNKP) is a dual specificity 5'-DNA kinase/3'-DNA phosphatase, with roles in base excision repair, DNA single-strand break repair and non-homologous end joining (NHEJ); yet precisely how PNKP functions in the repair of DNA double strand breaks (DSBs) remains unclear. We demonstrate that PNKP is phosphorylated by the DNA-dependent protein kinase (DNA-PK) and ataxia-telangiectasia mutated (ATM) in vitro. The major phosphorylation site for both kinases was serine 114, with serine 126 being a minor site. Ionizing radiation (IR)-induced phosphorylation of cellular PNKP on S114 was ATM dependent, whereas phosphorylation of PNKP on S126 required both ATM and DNA-PK. Inactivation of DNA-PK and/or ATM led to reduced PNKP at DNA damage sites in vivo. Cells exp...

Excitation-induced ataxin-3 aggregation in neurons from patients with Machado–Joseph disease

Nature AOP — Wed, 23 Nov 2011 05:00:00 +0100

Excitation-induced ataxin-3 aggregation in neurons from patients with Machado–Joseph disease Nature advance online publication 23 November 2011. doi:10.1038/nature10671 Authors: Philipp Koch, Peter Breuer, Michael Peitz, Johannes Jungverdorben, Jaideep Kesavan, Daniel Poppe, Jonas Doerr, Julia Ladewig, Jerome Mertens, Thomas Tüting, Per Hoffmann, Thomas Klockgether, Bernd O. Evert, Ullrich Wüllner & Oliver Brüstle Machado–Joseph disease (MJD; also called spinocerebellar ataxia type 3) is a dominantly inherited late-onset neurodegenerative disorder caused by expansion of polyglutamine (polyQ)-encoding CAG repeats in the MJD1 gene (also known as ATXN3). Proteolytic liberation of highly aggregation-prone polyQ fragments from the protective sequence of the MJD1...

Evaluation of anti‐nociceptive effect of epidural tramadol, tramadol‐lidocaine and lidocaine in goats

Veterinary Anaesthesia and Analgesia — Tue, 22 Nov 2011 05:00:00 +0100

Conclusions and clinical relevance The combination of tramadol‐lidocaine given by epidural injection produced an anti‐nociceptive effect in the perineal region, which was rapid in onset and had a longer duration of action than lidocaine alone. This combination might prove useful clinically to provide analgesia in goats for long‐duration obstetrical and surgical procedures but surgical stimuli were not investigated in this study. (Source: Veterinary Anaesthesia and Analgesia)

Development of a xylazine constant rate infusion with or without butorphanol for standing sedation of horses

Veterinary Anaesthesia and Analgesia — Tue, 22 Nov 2011 05:00:00 +0100

Conclusion Xylazine bolus, followed by CRI, provided constant sedation. Additional butorphanol was ineffective in reducing xylazine requirements and increased ataxia and apparent early recovery from sedation in unstimulated horses.Clinical relevance Data were obtained on unstimulated healthy horses and extrapolation to clinical conditions requires caution. (Source: Veterinary Anaesthesia and Analgesia)

Instability of syllable repetition in patients with spinocerebellar ataxia and Parkinson's disease

Movement Disorders — Tue, 22 Nov 2011 05:00:00 +0100

Conclusions:Cerebellar function may be required for the general precision of interval timing, whereas basal ganglia rather serve to maintain rhythm stability over time. © 2011 Movement Disorder Society (Source: Movement Disorders)

Fibromyalgia in fragile X mental retardation 1 gene premutation carriers

Rheumatology — Tue, 22 Nov 2011 05:00:00 +0100

Conclusion. Since FM affects 2–4% of the world's population and about 1 in 250 females are FMR1 carriers, a study screening females with FM for the presence of the FMR1 premutation is worthwhile. A finding of increased prevalence of FMR1 carriers among females with FM would impact the standard evaluation of FM. Presently, guidelines for FMR1 genetic testing includes early menopause, congenital intellectual disability, autism spectrum disorder, tremor or ataxia, and a family history of FXTAS or fragile X syndrome. The latter is a common cause of autism and developmental delay. Such testing is important because female carriers are at risk of having a child with fragile X syndrome. (Source: Rheumatology)

Lycopene inhibits Helicobacter pylori-induced ATM/ATR-dependent DNA damage response in gastric epithelial AGS cells.

Free Radical Biology and Medicine — Sun, 20 Nov 2011 05:00:00 +0100

In conclusion, lycopene may be beneficial for treatment of H. pylori-induced gastric diseases associated with oxidative DNA damage. PMID: 22178412 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)

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[Case Report] A strange case of waitress headache

LANCET — Sat, 19 Nov 2011 05:00:00 +0100

In September, 2010, a 21-year-old woman, who worked as a waitress at an Italian restaurant, presented to our neurological department with a sudden-onset, non-specific headache of moderate severity, which was unresponsive to over-the-counter medications. She also had vomiting and unsteadiness. 2 weeks before she had had a self-limited episode of febrile gastroenteritis. On admission, she was afebrile and she had horizontal nystagmus. Blood tests showed slight leucocytosis. Over the next 24 h, her neurological status worsened and she developed mild neck stiffness, bilateral cerebellar ataxia, and right-sided facial hypoaesthesia. (Source: LANCET)

Role and clinical significance of lymphocyte mitochondrial dysfunction in type 2 diabetes mellitus.

Translational Research : the journal of laboratory and clinical medicine — Fri, 18 Nov 2011 20:06:38 +0100

Authors: Khan S, Raghuram GV, Bhargava A, Pathak N, Chandra DH, Jain SK, Mishra PK Abstract Lymphocyte homeostasis in type 2 diabetes mellitus (T2DM) is associated with increased susceptibility to infections. Mitochondrial oxidative stress is implicated primarily in the immune pathophysiology of diabetes; however, the molecular underpinnings of lymphocyte mitochondrial dysfunction and ensuing downstream cellular effects are hitherto unreported. Both in early diagnosed patients and patients with late complications, we observed an inverse correlation between mitochondrial DNA content in lymphocytes and hemoglobin A1 (HbA1c) levels. This relation established for the first time might serve as a general, yet direct, predictor or indicator for mitochondrial dysfunction in T2DM. Compared ...

Ophthalmic features of Friedreich ataxia

Eye — Fri, 18 Nov 2011 08:00:00 +0100

Authors: S Noval, I Contreras, I Sanz-Gallego, R K Manrique & J Arpa (Source: Eye)

Paralytic Shellfish Poisoning in Alaska

The Poison Review — Fri, 18 Nov 2011 06:15:22 +0100

This report notes that of the 21 cases of PSP detected, 17 were not reported to the Alaska health authorities. This MMWR report brought to mind Sinead O’Connor’s haunting version of the classic Irish song “Molly Malone”: www.youtube.com/watch?v=3ouqhCtIh2g Related post: Saxitoxin invades Seattle! (Source: The Poison Review)

ImPRESsive hypertensive encephalopathy

Emergency Medicine Journal — Fri, 18 Nov 2011 05:00:00 +0100

A 67-year-old woman was admitted after having her first-ever epileptic seizure. Three days before, she started complaining of vertigo, gait disturbances and tension-type headache. Examination revealed obtundation, dysarthria and ataxia. Blood pressure was 300/123 mm Hg. Within 4 h, her consciousness deteriorated to deep coma. Brain MRI showed extensive vasogenic oedema with lesions in the cerebellum, brainstem, thalami, basal ganglia and cerebral cortex (figure 1A–E). Magnetic resonance angiography revealed stenosis of both renal arteries (figure 1F). Cerebrospinal fluid showed elevated protein (253 mg/dl) and lactate levels (39.3 mg/dl), and cell count was 7/μl. Because of cerebellar oedema and enlarged ventricular spaces, temporary ventricular drainage w...

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PP5 Regulates UV Light-induced Chk1 Phosphorylation [Cell Biology]

Journal of Biological Chemistry — Fri, 18 Nov 2011 05:00:00 +0100

PP5 is a ubiquitously expressed Ser/Thr protein phosphatase. High levels of PP5 have been observed in human cancers, and constitutive PP5 overexpression aids tumor progression in mouse models of tumor development. However, PP5 is highly conserved among species, and the roles of PP5 in normal tissues are not clear. Here, to help evaluate the biological actions of PP5, a Cre/loxP-conditional mouse line was generated. In marked contrast to the early embryonic lethality associated with the genetic disruption of other PPP family phosphatases (e.g. PP2A and PP4), intercrosses with mouse lines that ubiquitously express Cre recombinase starting early in development (e.g. MeuCre40 and ACTB-Cre) produced viable and fertile PP5-deficient mice. Phenotypic differences caused by the total disruption of ...

Activation of Mec1 by Dpb11 C Terminus [Signal Transduction]

Journal of Biological Chemistry — Fri, 18 Nov 2011 05:00:00 +0100

Budding yeast Dpb11 (human TopBP1, fission yeast Cut5) is an essential protein required for replisome assembly and for the DNA damage checkpoint. Previous studies with the temperature-sensitive dpb11–1 allele, truncated at amino acid 583 of the 764-amino acid protein, have suggested the model that Dpb11 couples DNA replication to the replication checkpoint. However, the dpb11–1 allele shows distinct replication defects even at permissive temperatures. Here, we determine that the 1–600-amino acid domain of DPB11 is both required and sufficient for full replication function of Dpb11 but that this domain is defective for activation of the principal checkpoint kinase Mec1 (human ataxia telangiectasia and Rad3-related) in vitro and in vivo. Remarkably, mutants of DPB11 that leave its repl...

Body Mass Index is Inversely Correlated with the Expanded CAG Repeat Length in SCA3/MJD Patients.

Cerebellum — Thu, 17 Nov 2011 05:00:00 +0100

In this report, we present evidence that low BMI is not only present in SCA3/MJD, but is also directly related to the length of the expanded CAG repeats, which is the causative mutation of the disease. This association points that weight loss might be a primary disturbance of SCA3/MJD, although further detailed analyses are necessary for a better understanding of the nutritional deficit and its role in the pathophysiology of SCA3/MJD. PMID: 22090366 [PubMed - as supplied by publisher] (Source: Cerebellum)

[Tripeptidyl peptidase 1 in patients with late infantile neuronal ceroid lipofuscinosis.]

Anales de Pediatria — Thu, 17 Nov 2011 05:00:00 +0100

CONCLUSIONS: The enzymatic diagnosis of late infantile neuronal ceroid lipofuscinoses from dried blood on filter paper card is a rapid, easier, less expensive and accurate molecular diagnosis tool. PMID: 22100780 [PubMed - as supplied by publisher] (Source: Anales de Pediatria)