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348 records returned

Fragment C of tetanus toxin, more than a carrier. Novel perspectives in non-viral ALS gene therapyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract The non-toxic carboxy-terminal fragment of tetanus toxin heavy chain (TTC) has been implicated in the activation of cascades responsible for trophic actions and neuroprotection by inhibition of apoptosis. Previous in vitro studies have described signalling pathways that underlie the administration of TTC to neurons. We investigated whether these properties were maintained in a mouse model of neurodegenerative disease. Naked DNA encoding for TTC was injected intramuscularly and neuromuscular function and clinical behaviour were monitored until endstage in the transgenic SOD1G93A mouse model that expr...
Source: Journal of Molecular Medicine - November 18, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Statins enhance peroxisome proliferator-activated receptor γ coactivator-1α activity to regulate energy metabolismEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we found that statins reduced the active form of Akt and enhanced PGC-1α activity. Specifically, statins failed to activate an S571A mutant of PGC-1α. The activation of PGC-1α by statins selectively enhanced the expression of energy metabolizing enzymes and regulators including peroxisome proliferator-activated receptor α, acyl-CoA oxidase, carnitine palmitoyl transferase-1A, and pyruvate dehydrogenase kinase 4. Importantly, a constitutively active form of Akt partially reduced the statin-enhanced gene expression. Our study thus provides a plausible mechanistic explanation for the hypolipidemic effe...
Source: Journal of Molecular Medicine - November 13, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Structural traces of past experience in the cerebral cortexEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract It is widely assumed that changes in the connections between neurons mediate the integration and storage of information in the brain and thereby underlie our ability to learn and remember. In particular, long-term memory is thought to rely on a structural reorganisation of neuronal circuits, but the proof for such a mechanism in the complex mammalian brain remains elusive. Recent advances in scientists' ability to follow structural dynamics of neuronal networks in the intact brain in vivo by means of 2-photon laser scanning microscopy has provided new insight into how information about new experienc...
Source: Journal of Molecular Medicine - November 10, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Cooperative effect of ribosomal protein s19 and Pim-1 kinase on murine c-Myc expression and myeloid/erythroid cellularityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Diamond-Blackfan anemia is a bone marrow failure syndrome associated with heterozygous mutations in the ribosomal protein S19 (RPS19) gene in a subgroup of patients. One of the interacting partners with RPS19 is the oncoprotein PIM-1 kinase. We intercrossed Rps19 +/− and Pim-1 −/− mice strains to study the effect from the disruption of both genes. The double mutant (Rps19 +/− Pim-1 −/− ) mice display normal growth with increased peripheral white and red blood cell counts when compared to the w.t. mice (Rps19 +/+ Pim-1 +/+ ). Molecular analysis of bone marrow cel...
Source: Journal of Molecular Medicine - November 8, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Neuroendocrine circuitry and endometriosis: progesterone derivative dampens corticotropin-releasing hormone-induced inflammation by peritoneal cells in vitroEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Clinical symptoms of endometriosis, such as pain and infertility, can be described as persistent stressors. Such continuous exposure to stress may severely affect the equilibrium and bidirectional communication of the endocrine and immune system, hereby further aggravating the progression of endometriosis. In the present study, we aimed to tease apart mediators that are involved in the stress response as well as in the progression of endometriosis. Women undergoing diagnostic laparoscopy due to infertility were recruited (n = 69). Within this cohort, early stage of endometriosis were diagnosed i...
Source: Journal of Molecular Medicine - November 7, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

The pneumococcus: why a commensal misbehavesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Several characteristics of Streptococcus pneumoniae (pneumococcus) combine to make it a particularly problematic pathogen. Firstly, the pneumococcus has the capacity to cause disease through the expression of virulence factors such as its polysaccharide capsule and pore-forming toxin. In addition, the pneumococcus is highly adaptable as demonstrated by its ability to acquire and disseminate resistance to multiple antibiotics. Although the pneumococcus is a major cause of disease, the organism is most commonly an “asymptomatic” colonizer of its human host (the carrier state), with transmission oc...
Source: Journal of Molecular Medicine - November 6, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Antagonism of α2A-adrenoceptor: a novel approach to inhibit inflammatory responses in sepsisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, modulation of the sympathetic nervous system by blocking α2A-AR appears to be a novel treatment for inflammatory conditions such as sepsis. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00109-009-0555-zAuthors Fangming Zhang, The Feinstein Institute for Medical Research Manhasset NY 11030 USARongqian Wu, The Feinstein Institute for Medical Research Manhasset NY 11030 USAXiaoling Qiang, The Feinstein Institute for Medical Research Manhasset NY 11030 USAMian Zhou, The Feinstein Institute for Medical Research Manhasset NY 11030 USAPing Wang, The Feinstein Institute for Medical Research...
Source: Journal of Molecular Medicine - November 5, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Blood cell generation from the hemangioblastEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Understanding how blood cells are generated is important from a biological perspective but also has potential implications in the treatment of blood diseases. Such knowledge could potentially lead to defining new conditions to amplify hematopoietic stem cells (HSCs) or could translate into new methods to produce HSCs, or other types of blood cells, from human embryonic stem cells or induced pluripotent stem cells. Additionally, as most key transcription factors regulating early hematopoietic development have also been implicated in various types of leukemia, understanding their function during norma...
Source: Journal of Molecular Medicine - October 24, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Monash at the academic industrial interface: trains and platformsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Content Type Journal ArticleCategory EditorialDOI 10.1007/s00109-009-0545-1Authors Alexander Ian Smith, Monash University Faculty of Medicine, Nursing and Health Sciences Clayton Victoria AustraliaPhillip R. Thompson, Monash University Faculty of Medicine, Nursing and Health Sciences Clayton Victoria AustraliaDavid P. Gearing, Monash University Faculty of Medicine, Nursing and Health Sciences Clayton Victoria Australia Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - October 22, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Controversies in cancer stem cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Content Type Journal ArticleCategory EditorialDOI 10.1007/s00109-009-0552-2Authors Richard J. Jones, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Room 244, Bunting-Blaustein Cancer Research Building, 1650 Orleans St. Baltimore MD 21231 USA Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - October 22, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Regulation of type 1 diabetes, tuberculosis, and asthma by parasitesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Helminth infection is a worldwide health problem. In addition to directly causing disease, helminthic infection also affects the incidence and progression of other diseases by exerting immune modulatory effects. In animal models, infection with helminthic parasites can prevent autoimmune diseases and allergic inflammatory diseases, but worsens protective immunity to certain infectious pathogens. In this review, we summarize current findings regarding the effects of helminth infection on type 1 diabetes, tuberculosis, and asthma and discuss possible mechanisms through which helminthic parasites modul...
Source: Journal of Molecular Medicine - October 21, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Photolytically generated nitric oxide inhibits caspase activity and results in AIF-mediated cell deathEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract In human skin tissue nitrite is found at relatively high concentrations and represents the main source for cutaneous non-enzymatic nitric oxide (NO) formation during UVA exposure due to photolytical decomposition. Since NO has been repeatedly shown to act pro- as well as anti-apoptotic we here studied the effects of UVA irradiation on human keratinocytes in the presence of nitrite. We show that UVA-induced nitrite photodecomposition effectively inactivated caspase activity. In parallel, we observed in human skin keratinocytes, UVA-irradiated in the presence of nitrite, a proteolytic processing of ap...
Source: Journal of Molecular Medicine - October 21, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Induction of Foxp3 demethylation increases regulatory CD4+CD25+ T cells and prevents the occurrence of diabetes in miceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract CD4+CD25+ regulatory T cells (Treg), a subpopulation of CD4+ T cells, regulate immune responses. Foxp3 is a key transcription factor for the development and function of Treg cells. During T-cell activation in vitro, a DNA demethylation agent 5-Aza-2′-deoxycytydine (DAC) can induce Foxp3 expression in CD4+CD25− Foxp3− cells via altering methylation status of a conserved element in the 5′-untranslated region of the Foxp3 gene. However, the effects of this agent on the development of Foxp3+ Treg cells in the thymus and in vivo are poorly understood. In the present study, a short-term treatment wit...
Source: Journal of Molecular Medicine - October 21, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Polymorphisms of the lamina maturation pathway and their association with the metabolic syndrome: the DESIR prospective studyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, we did not observe any convincing evidence that common polymorphisms of the lamina pathway could modulate the risk of MS. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00109-009-0548-yAuthors Benedicte Fontaine-Bisson, INSERM, UMR_S 937 75013 Paris FranceMarie-Christine Alessi, INSERM, UMR_S 626 13385 Marseille FranceNoemie Saut, INSERM, UMR_S 626 13385 Marseille FranceFrederic Fumeron, INSERM U695, Xavier Bichat Medical School Paris FranceMichel Marre, INSERM U695, Xavier Bichat Medical School Paris FranceAnne Dutour, INSERM, UMR_S 626 13385 Marseille FranceCatherine Badens, INSERM...
Source: Journal of Molecular Medicine - October 20, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Stem cells—meet immunityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract The ability of stem cells to differentiate into various different cell types holds great promise for the treatment of irreversible tissue damage that occurs in many debilitating conditions. With stem cell research advancing at a tremendous pace, it is becoming clear that one of the greatest hurdles to successful stem cell-derived therapies is overcoming immune rejection of the transplant. Although the use of immunosuppressive drugs can decrease the incidence of acute graft rejection, the burden of problems associated with prolonged immunosuppression must be reduced. Strategies inducing specific immu...
Source: Journal of Molecular Medicine - October 20, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

α- and β-Adducin polymorphisms affect podocyte proteins and proteinuria in rodents and decline of renal function in human IgA nephropathyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Adducins are cytoskeletal actin-binding proteins (α, β, γ) that function as heterodimers and heterotetramers and are encoded by distinct genes. Experimental and clinical evidence implicates α- and β-adducin variants in hypertension and renal dysfunction. Here, we have addressed the role of α- and β-adducin on glomerular function and disease using β-adducin null mice, congenic substrains for α- and β-adducin from the Milan hypertensive (MHS) and Milan normotensive (MNS) rats and patients with IgA nephropathy. Targeted deletion of β-adducin in mice reduced urinary protein excretion, precede...
Source: Journal of Molecular Medicine - October 16, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Translating the oxidative stress hypothesis into the clinic: NOX versus NOSEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Cardiovascular diseases remain the leading cause of death in industrialised nations. Since the pathomechanisms of most cardiovascular diseases are not understood, the majority of therapeutic approaches are symptom-orientated. Knowing the molecular mechanism of disease would enable more targeted therapies. One postulated underlying mechanism of cardiovascular diseases is oxidative stress, i.e. the increased occurrence of reactive oxygen species such as superoxide. Oxidative stress leads to a dysfunction of vascular endothelium-dependent protective mechanisms. There is growing evidence that this scena...
Source: Journal of Molecular Medicine - October 16, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Role of syndecan-3 polymorphisms in obesity and female hyperandrogenismEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract The heparan sulfate proteoglycan syndecan-3 (SDC3) is a novel regulator of feeding behavior and body weight. Recently, an association of SDC3 polymorphisms with obesity has been observed in Koreans. As female obesity is associated with hyperandrogenism and infertility, we studied the role of SDC3 polymorphisms in female individuals undergoing diagnostics prior to infertility treatment. For this purpose, endocrine parameters and body mass index of 249 women were assessed. Genotyping of V208I, D303N, and T329I was performed with TaqMan technology using lymphocyte-derived DNA and allelic discrimination ...
Source: Journal of Molecular Medicine - October 10, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Cancer stem cells—clinical relevanceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Therapeutic advances over the past three decades now allow most cancer patients to achieve major clinical responses. Although clinical responses can clearly decrease side effects and improve quality of life, most cancer patients still eventually relapse and die of their disease. Many cancers have now been shown to harbor cells that are phenotypically and biologically similar to normal cells with self-renewal capacity; these so-called cancer stem cells (CSC) typically constitute only a small fraction of the total tumor burden, but theoretically harbor all the self-renewal capacity. Moreover, the CSC ...
Source: Journal of Molecular Medicine - October 9, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Therapeutic targeting of signaling pathways in muscular dystrophyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Muscular dystrophy refers to a group of genetic diseases that cause severe muscle weakness and loss of skeletal muscle mass. Although research has helped understanding the molecular basis of muscular dystrophy, there is still no cure for this devastating disorder. Numerous lines of investigation suggest that the primary deficiency of specific proteins causes aberrant activation of several cell signaling pathways in skeletal and cardiac muscle leading to the pathogenesis of muscular dystrophy. Studies using genetic mouse models and pharmacological approaches have provided strong evidence that the mod...
Source: Journal of Molecular Medicine - October 9, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Polymorphisms within insulin-degrading enzyme (IDE) gene determine insulin metabolism and risk of type 2 diabetesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study validates and confirms the association of IDE polymorphisms with T2DM risk in the prospective German cohort and provides novel evidence of influences of IDE genetic variants on insulin metabolism. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00109-009-0540-6Authors Natalia Rudovich, Charité University Medicine Department of Internal Medicine, Division of Endocrinology, Diabetes, and Nutrition, Campus Benjamin Franklin Berlin GermanyOlga Pivovarova, German Institute of Human Nutrition Potsdam-Rehbruecke Department of Clinical Nutrition Nuthetal GermanyEva Fisher, German Institute of Hu...
Source: Journal of Molecular Medicine - October 7, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

TCF7L2 genetic variants and progression to diabetes in the Chinese population: pleiotropic effects on insulin secretion and insulin resistanceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract TCF7L2 genetic variants were associated with progression to type 2 diabetes in Europeans. However, the role of TCF7L2 in type 2 diabetes remained uncertain in Chinese. Seventeen tag single nucleotide polymorphisms were genotyped in 1,094 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance family study. At baseline, the rs7903146 T allele in the exon 4 linkage disequilibrium (LD) block were associated with lower insulinogenic index at 60 min (P = 0.01), while the rs290481 G allele near the 3′ end was associated with higher 2-h po...
Source: Journal of Molecular Medicine - October 6, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Phase II nonrandomized study of the efficacy and safety of COX-2 inhibitor celecoxib on patients with cancer cachexiaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Chronic inflammation is one of the main features of cancer cachexia. Experimental and clinical studies showed that cyclooxygenase-2 inhibitors, such as celecoxib, may be beneficial in counteracting major symptoms of this devastating syndrome. We carried out a prospective phase II clinical trial to test the safety and effectiveness of an intervention with the COX-2 inhibitor celecoxib (300 mg/day for 4 months) on key variables of cachexia (lean body mass, resting energy expenditure, serum levels of proinflammatory cytokines, and fatigue) in patients with advanced cancer at different sites. ...
Source: Journal of Molecular Medicine - October 3, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

T cell cross-talk with kidney dendritic cells in glomerulonephritisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract T cells have long been suspected to contribute to glomerulonephritis not only as helpers for antibody-producing B cells, but also as immune effector cells. Recent evidence has substantiated this hypothesis, by identifying tubulointerstitial dendritic cells (DCs) as crucial interaction partners. Kidney DCs capture glomerular antigens released for example by cytotoxic CD8+ T cells and present them to infiltrating CD4+ T helper cells. This cross-talk results in the production of proinflammatory cytokines and chemokines that recruit and activate further immune effector cells. Such immunocytes are the mai...
Source: Journal of Molecular Medicine - October 1, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Increased type IIA secretory phospholipase A2 expression contributes to oxidative stress in end-stage renal diseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract End-stage renal disease (ESRD) patients exhibit increased in vivo oxidative stress conceivably contributing to cardiovascular mortality. The type IIA secretory phospholipase A2 (sPLA2) has proatherogenic activity. We explored the hypothesis that sPLA2 contributes to oxidative stress generation and endothelial dysfunction in ESRD patients and transgenic (tg) mice. Patients with ESRD had increased in vivo oxidative stress as assessed by plasma isoprostane levels (p < 0.001). Active sPLA2 in plasma was substantially increased compared with healthy controls (1,156 ± 65 versus 184 ± 5 ...
Source: Journal of Molecular Medicine - October 1, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

MACC1 — more than metastasis? Facts and predictions about a novel geneEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract We recently identified the metastasis-associated in colon cancer 1 (MACC1) gene by a genome-wide search for differentially expressed genes in human colon cancer tissues, metastases, and normal tissues. Based on MACC1 expression in primary colon cancers, which did not present with metastases, our negative and positive prediction for metachronous metastasis was correct in 80% and 74% of cases, respectively. The 5-year-survival was 80% for MACC1 low expressors, but 15% for individuals who showed high MACC1 expression in their primary tumors. MACC1 induces migration, invasion and proliferation in cell c...
Source: Journal of Molecular Medicine - September 29, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

The mineralization phenotype in Abcc6−/− mice is affected by Ggcx gene deficiency and genetic background—a model for pseudoxanthoma elasticumEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we examined the hypothesis that the GGCX gene encoding γ-glutamyl carboxylase may interfere with the mineralization process in Abcc6 −/− mice. Thus, Abcc6 −/− and Ggcx +/− mice were generated on 129S1;C57 and 129S1;129X1;C57 genetic backgrounds, respectively, and backcrossed with C57BL/6J for five generations. Thus, these strains differ by the 129X1 contribution to the background of the mice. We then generated Abcc6 −/− ;Ggcx +/+ and Abcc6 −/− ;Ggcx +/− mice by crossing Abcc6 −/− and Ggcx +/− mice. The degree of mineralization of connective capsule of v...
Source: Journal of Molecular Medicine - September 29, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Brain cancer stem cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Cancers comprise heterogeneous cells, ranging from highly proliferative immature precursors to more differentiated cell lineages. In the last decade, several groups have demonstrated the existence of cancer stem cells in both nonsolid solid tumors, including some of the brain: glioblastoma multiforme (GBM), medulloblastoma, and ependymoma. These cells, like their normal counterpart in homologous tissues, are multipotent, undifferentiated, self-sustaining, yet transformed cells. In particular, glioblastoma-stem like cells (GBSCs) self-renew under clonal conditions and differentiate into neuron- and g...
Source: Journal of Molecular Medicine - September 29, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Preventing autoimmunity by regulating regulatory T-cell inductionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Content Type Journal ArticleCategory Clinical ImplicationsDOI 10.1007/s00109-009-0536-2Authors Friedrich Luft, Experimental and Clinical Research Center Berlin-Buch Germany Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - September 28, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Fine mapping of Plasmodium falciparum ribosomal phosphoprotein PfP0 revealed sequences with highly specific binding activity to human red blood cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, 16 20-mer-long synthetic peptides spanning the entire PfP0 sequence were evaluated by means of receptor–ligand assays with human red blood cells (RBCs) in order to determine the role played by these peptides in the invasion process. Four RBC high-activity binding peptides (HABPs), located mostly toward the N-terminal region, were identified: HABP 33898 (1MAKLSKQQKKQMYIEKLSSL20), HABP 33900 (41ASVRKSLRGKATILMGKNTRY60), HABP 33901 (61IRTALKKNLQAVPQIEKLLPY 80), and HABP 33906 (161LIKQGEKVTASSATLLRKFNY180). The binding pattern of HABPs 33898 and 33906 to enzyme-treated RBCs suggests receptors of protein na...
Source: Journal of Molecular Medicine - September 20, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Lysosomal ceramide mediates gemcitabine-induced death of glioma cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Acid sphingomyelinase-induced ceramide release has been shown by many studies to induce apoptosis in response to various stimuli. However, the mechanisms of acid sphingomyelinase/ceramide-mediated death signaling following treatment with chemotherapeutic drugs have not been fully elucidated thus far. The present study demonstrates that treatment of glioma cells with clinically achievable doses of gemcitabine results in acid sphingomyelinase activation, lysosomal accumulation of ceramide, cathepsin D activation, Bax insertion into the mitochondria, and cell death. Pharmacological inhibition or geneti...
Source: Journal of Molecular Medicine - September 17, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Disease mutations in the “head” domain of the extra-sarcomeric protein desmin distinctly alter its assembly and network-forming propertiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract The intermediate filament protein desmin generates an extra-sarcomeric network in myocytes. Mutations in the desmin gene cause myofibrillar myopathy characterized by desmin-positive aggregates and myofibrillar dissolution. Past analysis revealed that the non-α-helical amino-terminal “head” domain of desmin is a vital coordinator of protein assembly. We have now characterized assembly and network-forming properties of five recently discovered myopathy-causing mutations residing in this domain. In vitro analyses with recombinant proteins show that two mutant variants residing in a conserved nonap...
Source: Journal of Molecular Medicine - September 17, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Post-translationally modified T cell epitopes: immune recognition and immunotherapyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract The functionality of proteins is greatly extended by a diverse array of post-translational modifications (PTMs), many of which are recognized by the immune system. Notably, a significant proportion of peptides presented to T cells by the major histocompatibility complex in vivo are post-translationally modified. Since the cellular mechanisms that introduce and control protein modifications can differ between health and disease, the associated changes in antigen presentation have the potential to alter immune responses. A number of such situations have been implicated with infection, inflammation, au...
Source: Journal of Molecular Medicine - September 17, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Benzyl isothiocyanate exhibits anti-inflammatory effects in murine macrophages and in mouse skinEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study examined whether BITC inhibits lipopolysaccharide (LPS)-induced inflammatory responses in Raw 264.7 macrophages and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema formation. The treatment of macrophages with various concentrations of BITC resulted in a dose-dependent reduction in the LPS-induced secretion of interleukin (IL)-1β, TNF-α, and IL-6 and their corresponding mRNA levels, as well as in the production of nitric oxide and PGE2. Consistent with these findings, BITC inhibited the LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 proteins and the...
Source: Journal of Molecular Medicine - September 17, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Cancer stem cells: controversies in multiple myelomaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Increasing data suggest that the initiation, relapse, and progression of human cancers are driven by specific cell populations within an individual tumor. However, inconsistencies have emerged in precisely defining phenotypic markers that can reliably identify these “cancer stem cells” in nearly every human malignancy studied to date. Multiple myeloma, one of the first tumors postulated to be driven by a rare population of cancer stem cells, is no exception. Similar to other diseases, controversy surrounds the exact phenotype and biology of multiple myeloma cells with the capacity for clonogenic...
Source: Journal of Molecular Medicine - September 17, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Therapeutic potential of olfactory ensheathing cells in neurodegenerative diseasesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract The regenerative capacity of the olfactory system has generated interest in potential clinical application of cells from the olfactory epithelium in the treatment of neurodegenerative diseases. Experimental evidence from animal models and clinical studies suggest that transplantation of olfactory ensheathing cells (OEC), specialized glia in the olfactory system, may be therapeutically useful in neurodegenerative diseases such as spinal cord injury and stroke. This review article describes the different experimental approaches in OEC transplantation. We also discuss the possible effects of OEC implan...
Source: Journal of Molecular Medicine - September 15, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Modulation of bone marrow stromal cell functions in infectious diseases by toll-like receptor ligandsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Bone marrow-derived stromal cells (BMSCs, or as they are frequently referred to as mesenchymal stem cells) have been long known to support hematopoiesis and to regenerate bone, cartilage, and adipose tissue. In the last decade, however, a vast amount of data surfaced in the literature to suggest new roles for these cells including tissue regeneration and immunomodulation. A great number of review articles appeared that summarize these new data and focus on different aspects of the physiology of these cells. In this present short review, we will try to summarize the available data based on both mouse...
Source: Journal of Molecular Medicine - September 15, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

A novel mechanism for inflammation-associated carcinogenesis; an important role of activation-induced cytidine deaminase (AID) in mutation inductionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Inflammation is a risk for cancer development; however, its mechanism is unknown. Recent studies have revealed that activation-induced cytidine deaminase (AID), which plays essential roles in both class-switch recombination and somatic hypermutation of immunoglobulin gene in B lymphocytes, is aberrantly expressed in non-lymphoid cells not only by H.pylori and HCV infection but also by various proinflammatory cytokines, leading to the generation of gene mutations. These findings not only suggested a new mechanism of inflammation-associated carcinogenesis but has also opened up a new field of tumor bio...
Source: Journal of Molecular Medicine - September 15, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Sgk1 activates MDM2-dependent p53 degradation and affects cell proliferation, survival, and differentiationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Serum and glucocorticoid regulated kinase 1 (Sgk1) is a serine–threonine kinase that is activated by serum, steroids, insulin, vasopressin, and interleukin 2 at the transcriptional and post-translational levels. Sgk1 is also important in transduction of growth factors and steroid-dependent survival signals and may have a role in the development of resistance to cancer chemotherapy. In the present paper, we demonstrate that Sgk1 activates MDM2-dependent p53 ubiquitylation. The results were obtained in RKO cells and other cell lines by Sgk1-specific RNA silencing and were corroborated in an original...
Source: Journal of Molecular Medicine - September 15, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Translational research of novel hormones: lessons from animal models and rare human diseases for common human diseasesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Since the 1980s, a number of bioactive molecules, now known as cardiovascular hormones, have been isolated from the heart and blood vessels, particularly from the subset of vascular endothelial cells. The natriuretic peptide family is the prototype of the cardiovascular hormones. Over the following decade, a variety of hormones and cytokines, now known as adipokines or adipocytokines, have also been isolated from adipose tissue. Leptin is the only adipokine demonstrated to cause an obese phenotype in both animals and humans upon deletion. Thus, the past two decades have seen the identification of tw...
Source: Journal of Molecular Medicine - September 15, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Colon cancer stem cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Colorectal cancer (CRC) is the third most common form of cancer and the second cause of cancer-related death in the Western world, leading to 655,000 deaths worldwide per year (Jemal et al. in CA Cancer J Clin 56:106–130, 2006). Despite the emergence of new targeted agents and the use of various therapeutic combinations, none of the treatment options available is curative in patients with advanced cancer. A growing body of evidence is increasingly supporting the idea that human cancers can be considered as a stem cell disease. According to the cancer stem cell model, malignancies originate from a ...
Source: Journal of Molecular Medicine - September 3, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Small-molecule costimulatory blockade: organic dye inhibitors of the CD40–CD154 interactionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Costimulatory blockade is one of the most promising therapeutic targets in autoimmune diseases as well as in transplant recipients, and inhibition of the cluster of differentiation (CD)40–CD154 interaction, which is required for T cell activation and development of an effective immune response, is particularly promising in islet transplant recipients. Here, we report the ability of several small-molecule organic dyes to concentration dependently inhibit this interaction with IC50 values in the low-micromolar range. They were found to be considerably more active in inhibiting this interaction than t...
Source: Journal of Molecular Medicine - August 26, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Aneurysm formation and bradykininEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Content Type Journal ArticleCategory Clinical ImplicationsDOI 10.1007/s00109-009-0517-5Authors Friedrich C. Luft, Experimental and Clinical Research Center Berlin Germany Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine)
Source: Journal of Molecular Medicine - August 26, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

ATF3 transcription factor and its emerging roles in immunity and cancerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Activating transcription factor 3 (ATF3) is a member of the ATF/cyclic AMP response element-binding (ATF/CREB) family of transcription factors. It is an adaptive-response gene that participates in cellular processes to adapt to extra- and/or intracellular changes, where it transduces signals from various receptors to activate or repress gene expression. Advances made in understanding the immunobiology of Toll-like receptors have recently generated new momentum for the study of ATF3 in immunity. Moreover, the role of ATF3 in the regulation of the cell cycle and apoptosis has important implications fo...
Source: Journal of Molecular Medicine - August 24, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

The primacy of CD8 T lymphocytes in type 1 diabetes and implications for therapiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Type I diabetes (TID) is an autoimmune disease in which insulin-secreting beta cells of the pancreatic islets are destroyed by T lymphocytes. Until the 1990s, the prevailing dogma was that the attack was attributable to rogue T lymphocytes bearing CD4 markers on their surface (CD4 T helper lymphocytes). Today, the prevailing view is that rogue T cells bearing CD8 markers or cytotoxic CD8 T lymphocytes are also important and perhaps the foremost contributors to beta-cell death. Recognizing CD8 T-cell subsets as the prime culprits has helped to trace the disease's pathogenesis to abnormal T-cell educa...
Source: Journal of Molecular Medicine - August 20, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa, is protective in a murine model of colitisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, cannabidiol, a likely safe compound, prevents experimental colitis in mice. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00109-009-0512-xAuthors Francesca Borrelli, University of Naples Federico II Department of Experimental Pharmacology via D Montesano 49 80131 Naples ItalyGabriella Aviello, University of Naples Federico II Department of Experimental Pharmacology via D Montesano 49 80131 Naples ItalyBarbara Romano, University of Naples Federico II Department of Experimental Pharmacology via D Montesano 49 80131 Naples ItalyPierangelo Orlando, National Research Council Institute of ...
Source: Journal of Molecular Medicine - August 19, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Prognostic significance of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor expression in patients with breast cancerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis upon binding to TRAIL receptors 1 and 2 (TRAIL-R1/DR4 and TRAIL-R2/DR5). TRAIL-R3 (DcR1) and TRAIL-R4 (DcR2) have no or only a truncated cytoplasmic death domain. Consequently, they cannot induce apoptosis and instead have been proposed to inhibit apoptosis induction by TRAIL. Agonists for the apoptosis-inducing TRAIL-R1 and TRAIL-R2 are currently tested in clinical trials. To determine the expression pattern of all surface-bound TRAIL receptors and their prognostic clinical value, we investigated tumour samples of 311 patients with bre...
Source: Journal of Molecular Medicine - August 12, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

The implications of fetal programming of glomerular number and renal functionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Large epidemiological studies suggest a clear relation between low birth weight and adverse renal outcomes evident as early as during childhood. Such adverse outcomes may include glomerular disease, hypertension, and renal failure. Data from autopsy material and from experimental models suggest that reduction in nephron number via diminished nephrogenesis may be a major mechanism, and factors that lead to this reduction are incompletely elucidated. Other mechanisms appear to be renal (e.g., via the intrarenal renin–angiotensin–aldosterone system) and nonrenal (e.g. changes in endothelial functio...
Source: Journal of Molecular Medicine - August 12, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Thyroid peroxidase forms thionamide-sensitive homodimers: relevance for immunomodulation of thyroid autoimmunityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Thyroid peroxidase (TPO) is the key enzyme in thyroid hormone production and a universal autoantigen in Graves’ and other autoimmune thyroid diseases. We wished to explore the expression of TPO and whether it was affected by thionamide antithyroid drugs. We studied recombinant TPO, stably expressed by a Chinese hamster ovary cell line (CHO-TPO) and transiently expressed TPO-enhanced green fluorescent protein (eGFP) and -FLAG fusion proteins. Immunoblotting of CHO-TPO cell extracts showed high-molecular weight (HMW) TPO isoforms that were resistant to reduction, as well as 110 kDa monomeric TP...
Source: Journal of Molecular Medicine - August 9, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals

Role of telomere dysfunction in aging and its detection by biomarkersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract Aging is a complex process that has been shown to be linked to accumulation of DNA damage. Telomere shortening represents a cell-intrinsic mechanism leading to DNA damage accumulation and activation of DNA damage checkpoints in aging cells. Activation of DNA damage checkpoints in response to telomere dysfunction results in induction of cellular senescence—a permanent cell cycle arrest. Senescence represents a tumor suppressor mechanism protecting cells from evolution of genomic instability and transformation. As a drawback, telomere shortening may also limit tissue renewal and regenerative capacit...
Source: Journal of Molecular Medicine - August 9, 2009 Category: Molecular Biology Tags: Journal of Molecular Medicine Source Type: journals