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Potential Clinical Implications (potential + clinical_implication)
Selected AbstractsDistinctiveness of the cagA Genotype in Children and Adults with Peptic Symptoms in South ChinaHELICOBACTER, Issue 4 2009Juan Li Abstract Background:,Helicobacter pylori infection is different between children and adults, not only in infection rate but also in virulence genotypes. However, the 3, region of CagA, important in stomach carcinogenesis, still remains unclear in children. The present study aims to compare the frequency of cagA and the distribution of its subtypes between children and adults in South China. Materials and Methods:, One hundred and twenty-eight children and 99 adults with peptic symptoms were enrolled in our research. Histology, rapid urease test, and real-time polymerase chain reaction (PCR) assay were used to diagnose H. pylori infection. vacA s1 was detected by real-time PCR, and EPIYA motifs in the 3, region of CagA by conventional PCR and DNA sequencing. Results:,H. pylori infection was diagnosed in 53 children and 62 adults. vacA s1 was identified in 90.6% and 91.9% of infected children and adults, respectively. Furthermore, cagA was identified in 73.6% and 82.3% of infected children and adults, respectively. No patient with multiple cagA subtypes was observed. A higher prevalence of more virulent cagA genotype was found in children compared to adults (p < .05). Thirty-eight of 39 (97.4%) cagA -positive children were found to have EPIYA-ABD and only one (2.6%) with EPIYA-ABC. In adults, four types of EPIYA motifs , ABC (29.4%), ABD (64.7%), ABAB (2%), and AAD (3.9%) , were identified, and the ABD type was found more commonly in severe diseases, such as atrophic gastritis (53.3%) and gastric cancer (71.4%). Conclusion:,cagA genotypes in children and in adults are different, and EPIYA-ABD may have potential clinical implication in the development of gastric cancer in South China. [source] Aberrant hypertrophy in Smad3-deficient murine chondrocytes is rescued by restoring transforming growth factor ,,activated kinase 1/activating transcription factor 2 signaling: A potential clinical implication for osteoarthritisARTHRITIS & RHEUMATISM, Issue 8 2010Tian-Fang Li Objective To investigate the biologic significance of Smad3 in the progression of osteoarthritis (OA), the crosstalk between Smad3 and activating transcription factor 2 (ATF-2) in the transforming growth factor , (TGF,) signaling pathway, and the effects of ATF-2 overexpression and p38 activation in chondrocyte differentiation. Methods Joint disease in Smad3-knockout (Smad3,/,) mice was examined by microfocal computed tomography and histologic analysis. Numerous in vitro methods including immunostaining, real-time polymerase chain reaction, Western blotting, an ATF-2 DNA-binding assay, and a p38 kinase activity assay were used to study the various signaling responses and protein interactions underlying the altered chondrocyte phenotype in Smad3,/, mice. Results In Smad3,/, mice, an end-stage OA phenotype gradually developed. TGF,-activated kinase 1 (TAK1)/ATF-2 signaling was disrupted in Smad3,/, mouse chondrocytes at the level of p38 MAP kinase (MAPK) activation, resulting in reduced ATF-2 phosphorylation and transcriptional activity. Reintroduction of Smad3 into Smad3,/, cells restored the normal p38 response to TGF,. Phosphorylated p38 formed a complex with Smad3 by binding to a portion of Smad3 containing both the MAD homology 1 and linker domains. Additionally, Smad3 inhibited the dephosphorylation of p38 by MAPK phosphatase 1 (MKP-1). Both ATF-2 overexpression and p38 activation repressed type X collagen expression in wild-type and Smad3,/, chondrocytes. P38 was detected in articular cartilage and perichondrium; articular and sternal chondrocytes expressed p38 isoforms ,, ,, and ,, but not ,. Conclusion Smad3 is involved in both the onset and progression of OA. Loss of Smad3 abrogates TAK1/ATF-2 signaling, most likely by disrupting the Smad3,phosphorylated p38 complex, thereby promoting p38 dephosphorylation and inactivation by MKP-1. ATF-2 and p38 activation inhibit chondrocyte hypertrophy. Modulation of p38 isoform activity may provide a new therapeutic approach for OA. [source] Expression of angiogenic factors in chronic myeloid leukaemia: role of the bcr/abl oncogene, biochemical mechanisms, and potential clinical implicationsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2004C. Sillaber Abstract Chronic myeloid leukaemia (CML) is a stem cell disease characterized by an increased production and accumulation of clonal BCR/ABL,positive cells in haematopoietic tissues. The chronic phase of CML is inevitably followed by an accelerated phase of the disease, with consecutive blast crisis. However, depending on genetic stability, epigenetic events, and several other factors, the clinical course and survival appear to vary among patients. Recent data suggest that angiogenic cytokines such as vascular endothelial growth factor (VEGF), are up-regulated in CML, and play a role in the pathogenesis of the disease. These factors appear to be produced and released in leukaemic cells in patients with CML. In line with this notion, increased serum-levels of angiogenic growth factors are measurable in CML patients. In this study we provide an overview of angiogenic growth factors expressed in CML cells, discuss the possible pathogenetic role of these cytokines, the biochemical basis of their production in leukaemic cells, and their potential clinical implications. [source] Pharmacogenetic of response efficacy to antipsychotics in schizophrenia: pharmacodynamic aspects.FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2010Review, implications for clinical research Abstract Pharmacogenetics constitutes a new and growing therapeutic approach in the identification of the predictive factors of the response to antipsychotic treatment. This review aims to summarize recent finding into pharmacodynamic approach of pharmacogenetics of antipsychotics and particularly second generation. Studies were identified in the MEDLINE database from 1993 to July 2008 by combining the following Medical Subject Heading search terms: genetic, polymorphism, single nucleotide polymorphism, pharmacogenetics, antipsychotics, and response to treatment as well as individual antipsychotics names. Only pharmacodynamics studies were analyzed and we focused on efficacy studies. We also reviewed the references of ll identified articles. Most studies follow a polymorphism-by-polymorphism approach, and concern polymorphisms of genes coding for dopamine and serotonin receptors. Haplotypic approach has been considered in some studies. Few have studied the combinations of polymorphisms of several genes as a predictive factor of the response to antipsychotics. We present this gene-by-gene approach while detailing the features of the polymorphisms being studied (functionality, linkage disequilibrium) and the features of the studies (studied treatment(s), prospective/retrospective study, pharmacological dosage). We discuss the heterogeneity of the results and their potential clinical implications and extract methodological suggestions for the future concerning phenotype characterization, genotypes variants studied and methodological and statistical approach. [source] LAPTM4B-35 is a novel prognostic factor of hepatocellular carcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 5 2010Hua Yang MD Abstract Background LAPTM4B-35 is a 35-kDa tetra-transmembrane protein overexpressed in hepatocellular carcinoma (HCC) and promotes cell survival, proliferation, and tumorigenesis. However, the potential clinical implications of LAPTM4B-35 in HCC are still unclear. This study is aimed to investigate the correlations between LAPTM4B-35 expression and prognosis in patients with HCC. Methods Western blot and immunohistochemistry assays were used to determine the expression of LAPTM4B-35 in HCCs and their paired noncancerous liver tissues from 65 patients. The correlations of LAPTM4B-35 expression with clinicopathological parameters were assessed by Chi-square test. Patient survival was determined by Kaplan,Meier method and log-rank test. Cox regression was adopted for multivariate analysis of prognostic factors. Results LAPTM4B-35 overexpression occurred in 76.9% of HCC tissues, while only in 4.6% of noncancerous liver tissues. Overexpression of LAPTM4B-35 was significantly associated with TNM staging and invasive tumors. Patients with higher LAPTM4B-35 expression had significantly poorer overall survival (OS) and disease-free survival (DFS) (both P,<,0.001). On multivariate analysis, elevated expression of LAPTM4B-35 was found to be an independent prognostic factor for OS and DFS (P,=,0.009, 0.043, respectively). Conclusions LAPTM4B-35 overexpression is an independent prognostic factor for OS and DFS of HCC. J. Surg. Oncol. 2010; 101:363,369. © 2010 Wiley-Liss, Inc. [source] Anti-inflammatory properties of local anesthetics and their present and potential clinical implicationsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2006J. Cassuto Development of new local anesthetic agents has been focused on the potency of their nerve-blocking effects, duration of action and safety and has resulted in a substantial number of agents in clinical use. It is well established and well documented that the nerve blocking effects of local anesthetics are secondary to their interaction with the Na+ channels thereby blocking nerve membrane excitability and the generation of action potentials. Accumulating data suggest however that local anesthetics also posses a wide range of anti-inflammatory actions through their effects on cells of the immune system, as well as on other cells, e.g. microorganisms, thrombocytes and erythrocytes. The potent anti-inflammatory properties of local anesthetics, superior in several aspects to traditional anti-inflammatory agents of the NSAID and steroid groups and with fewer side-effects, has prompted clinicians to introduce them in the treatment of various inflammation-related conditions and diseases. They have proved successful in the treatment of burn injuries, interstitial cystitis, ulcerative proctitis, arthritis and herpes simplex infections. The detailed mechanisms of action are not fully understood but seem to involve a reversible interaction with membrane proteins and lipids thus regulating cell metabolic activity, migration, exocytosis and phagocytosis. [source] Nitric oxide in liver transplantation: Pathobiology and clinical implicationsLIVER TRANSPLANTATION, Issue 1 2003Vijay Shah MD The gaseous molecule nitric oxide is involved in a variety of liver transplant,relevant processes, including ischemia-reperfusion injury, acute cellular rejection, and circulatory changes characteristic of advanced liver disease. This review article focuses on new advances relating to the role of nitric oxide in these syndromes with an emphasis on pathobiology and potential clinical implications. [source] Inhibition of interferon-,-induced nitric oxide production in endotoxin-activated macrophages by cytolethal distending toxinMOLECULAR ORAL MICROBIOLOGY, Issue 5 2008K. P. S. Fernandes Introduction:, Cytolethal distending toxin (CDT) is a DNA-targeting agent produced by certain pathogenic gram-negative bacteria such as the periodontopathogenic organism Aggregatibacter actinomycetemcomitans. CDT targets lymphocytes and other cells causing cell cycle arrest and apoptosis, impairing the host immune response and contributing to the persistence of infections caused by this microorganism. In this study we explored the effects of CDT on the innate immune response, by investigating how it affects production of nitric oxide (NO) by macrophages. Methods:, Murine peritoneal macrophages were stimulated with Escherichia coli sonicates and NO production was measured in the presence or not of active CDT. Results:, We observed that CDT promptly and significantly inhibited NO production by inducible nitric oxide synthase (iNOS) in a dose-dependent manner. This inhibition is directed towards interferon-,-dependent pathways and is not mediated by either interleukin-4 or interleukin-10. Conclusion:, This mechanism may constitute an important aspect of the immunosuppression mediated by CDT and may have potential clinical implications in A. actinomycetemcomitans infections. [source] Increases in P-Wave Duration and Dispersion After Hemodialysis Are Totally (or Partially) Due to the Procedure-Induced Alleviation of the Body Fluid Overload: A Hypothesis with Strong Experimental SupportANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2005John E. Madias M.D. Increases in the P-wave duration (P-du) and P-wave dispersion (P-d) following hemodialysis (HD) are attributed to changes in the electrolytic milieu with HD, or are considered to be due to an unknown mechanism. Such changes are thought to be proarrhythmic, and thus have potential clinical implications. Increase in the amplitude of QRS complexes following HD has been amply documented in the literature. Also, recent work linking attenuation/augmentation of amplitude of QRS and P-wave complexes in patients with increase/subsequent decrease weights due to anasarca peripheral edema/and its alleviation, or before/after hemodialysis (HD) suggests that the increase in the P-du and P-d after HD may be totally (or partially) mediated by the alleviation of the fluid overload by the procedure. This is supported by the decrease/increase in the QRS duration noted with anasarca/and its alleviation. To further clarify this issue, and prove or refute the above hypothesis, it is recommended that correlations of changes in the P-du and P-d with the loss of weight or net fluid dialyzed are carried out, in addition to the traditional considerations of electrolytic alterations after HD. [source] Can preoperative bevacizumab improve trabeculectomy outcome?ACTA OPHTHALMOLOGICA, Issue 2009Avastin-Trab study Purpose The aim of this project is to study whether peroperative intracameral bevacizumab (Avastin®) might improve the outcome of filtration surgery. Methods This study will be carried out in a prospective, placebo-controlled, double-blinded experimental setup. The effect of peroperative administration of bevacizumab on intraocular pressure, bleb characteristics and post-operative medication and surgical intervention will be investigated. The risk of systemic side-effects will minimalized by using local anti-Vascular Endothelial Growth Factor treatment. The study patients will be divided into two major groups: A) Patients with primary open angele glaucoma and B) Patients with normotensive glaucoma, in which very low IOPs are targeted. Both groups of patients will undergo a trabeculectomy. Patients in group A will not be given the antimetabolite Mitomycin C (MMC), while patients in group B will receive MMC to obtain sufficiently low IOPs. This strategy adheres to standard operating procedures for filtration surgery. Results will follow Conclusion Our study will potentially shed new light on a plausible and simple method to improve the prognosis of glaucoma filtration surgery. Since this study will provide direct data on the effectiveness of a one-time treatment that might reduce the risk of bleb failure after filtration surgery, avoiding or reducing the need for long-term medication use or secondary surgical intervention, the potential clinical implications of this study are clear. Thus, our project opens exciting new perspectives for the treatment and prognosis of the blinding condition of glaucoma [source] Immune function in hypopituitarism: time to reconsider?CLINICAL ENDOCRINOLOGY, Issue 4 2010Annice Mukherjee Summary Hypopituitarism is not currently considered as a potential cause of immune disruption in humans. Accumulating data from in vitro and animal models support a role for the pituitary gland in immune regulation. Furthermore, the increased mortality risk noted in patients with adult hypopituitarism remains poorly explained and immune dysfunction could conceivably contribute to this observation. In a recent issue of Clinical & Experimental Immunology, we presented new data relating to immune status in adults with treated, severe hypopituitarism. We observed humoral immune deficiency in a significant proportion, despite stable pituitary replacement, including growth hormone (GH). This was especially evident in those with low pretreatment IGF-I levels and appeared independent of anticonvulsant use or corticosteroid replacement. These observations require substantiation with future studies. In this short review, we summarize existing data relating to the effects of pituitary hormones on immune function and discuss potential clinical implications surrounding the hypothesis of immune dysregulation in severe hypopituitarism. [source] Ghrelin: more than a natural GH secretagogue and/or an orexigenic factorCLINICAL ENDOCRINOLOGY, Issue 1 2005E. Ghigo Summary Ghrelin, an acylated peptide produced predominantly by the stomach, has been discovered to be a natural ligand of the growth hormone secretagogue receptor type 1a (GHS-R1a). Ghrelin has recently attracted considerable interest as a new orexigenic factor. However, ghrelin exerts several other neuroendocrine, metabolic and also nonendocrine actions that are explained by the widespread distribution of ghrelin and GHS-R expression. The likely existence of GHS-R subtypes and evidence that the neuroendocrine actions, but not all the other actions, of ghrelin depend on its acylation in serine-3 revealed a system whose complexity had not been completely explored by studying synthetic GHS. Ghrelin secretion is mainly regulated by metabolic signals and, in turn, the modulatory action of ghrelin on the control of food intake and energy metabolism seems to be among its most important biological actions. However, according to a recent study, ghrelin-null mice are neither anorectics nor dwarfs and this evidence clearly depicts a remarkable difference from leptin null mice. Nevertheless, the original and fascinating story of ghrelin, as well as its potential pathophysiological implications in endocrinology and internal medicine, is not definitively cancelled by these data as GHS-R1a null aged mice show significant alterations in body composition and growth, in glucose metabolism, cardiac function and contextual memory. Besides potential clinical implications for natural or synthetic ghrelin analogues acting as agonists or antagonists, there are several open questions awaiting an answer. How many ghrelin receptor subtypes exist? Is ghrelin ,the' or just ,a' GHS-R ligand? That is, are there other natural GHS-R ligands? Is there a functional balance between acylated and unacylated ghrelin forms, potentially with different actions? Within the next few years suitable answers to these questions will probably be found, making it possible to gain a better knowledge of ghrelin's potential clinical perspectives. [source] | ||||||||||