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C Disease (c + disease)
Selected AbstractsOxidative stress in NPC1 deficient cells: protective effect of allopregnanoloneJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 9b 2009Stefania Zampieri Abstract Niemann-Pick C disease (NPC) is an autosomal recessive neurodegenerative disorder caused by the abnormal function of NPC1 or NPC2 proteins, leading to an accumulation of unesterified cholesterol and glycosphingolipids (GSLs) in the lysosomes. The mechanisms underlying the pathophysiology in NPC disease are not clear. Oxidative damage is implicated in the pathophysiology of different neurological disorders and the effect of GSL accumulation on the intracellular redox state has been documented. Therefore, we determined whether the intracellular redox state might contribute to the NPC disease pathophysiology. Because the treatment of NPC mice with allopregnanolone (ALLO) increases their lifespan and delays the onset of neurological impairment, we analysed the effect of ALLO on the oxidative damage in human NPC fibroblasts. Concentrations of reactive oxygen species (ROS) and lipid peroxidation were higher in fibroblasts from NPC patients than in fibroblasts from normal subjects. Fibroblasts from NPC patients were more susceptible to cell death through apoptosis after an acute oxidative insult. This process is mediated by activation of the NF-,B signalling pathway. Knockdown of NPC1 mRNA both in normal fibroblasts and in human SH-SY5Y neuroblastoma cells caused increased ROS concentrations. ALLO treatment of fibroblasts from NPC patients or NPC1 knockdown cells reduced the levels of ROS and lipid peroxidation and prevented peroxide-induced apoptosis and NF-kB activation. Thus, these findings suggest that oxidative stress might contribute to the NPC disease and ALLO might be beneficial in the treatment of the disease, at least in part, due to its ability to restore the intracellular redox state. [source] Altered apolipoprotein E glycosylation is associated with A,(42) accumulation in an animal model of Niemann-Pick Type C diseaseJOURNAL OF NEUROCHEMISTRY, Issue 6 2010Ching-Ching Chua J. Neurochem. (2010) 112, 1619,1626. Abstract Neurodegeneration is the final cause of death in Niemann-Pick Type C (NPC) disease, a cholesterol-storage disorder. Accumulating evidence indicates that NPC may share common pathological mechanisms with Alzheimer's disease, including the link between aberrant cholesterol metabolism and amyloid-, (A,) deposition. Apolipoprotein E (apoE) is highly expressed in the brain and plays a pivotal role in cholesterol metabolism. ApoE can also modulate A, production and clearance, and it is a major genetic risk factor for Alzheimer's disease. Although apoE is glycosylated, the functional significance of this chemical alteration on A, catabolism is unclear. In this study using an NPC animal model, we detect specific changes in apoE glycosylation that correlate with increased A,(42) accumulation prior to the appearance of neurological abnormalities. This suggests that increased apoE expression could be a compensatory response to the increased A,(42) deposition in NPCnih mice. We also observe what appears to be a simplification of the glycosylation process on apoE during neurodegeneration. [source] Clinical improvement in patients with decompensated liver disease caused by hepatitis B after treatment with lamivudineLIVER TRANSPLANTATION, Issue 6 2000Craig A. Sponseller Lamivudine is effective in inhibiting hepatitis B virus (HBV) replication, and its clinical use in patients with chronic hepatitis B is associated with improvements in serum aminotransferase levels and liver histopathologic characteristics. Few data are available on its use in patients with advanced liver disease. We report on the outcomes of 5 patients with hepatic decompensation caused by chronic hepatitis B treated long term with lamivudine. All patients were adult white men seropositive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) before therapy. All 5 patients had biopsy-proven cirrhosis with clinical and biochemical evidence of hepatic decompensation. Two patients had Child's class C cirrhosis; 2 patients, class B; and 1 patient, class A (although this patient had persistent portasystemic encephalopathy and developed variceal bleeding). HBV DNA became undetectable in all patients and remained so throughout the study. Both patients with Child's class C and 1 patient with class B cirrhosis had significant clinical improvement. Child-Pugh scores improved from 12 to 7 and 11 to 7 in the 2 patients with Child's class C cirrhosis, and the patient with class B cirrhosis had complete resolution of troublesome encephalopathy. Serum aminotransferase, albumin, and total bilirubin levels improved significantly in 3 of 5 patients. One patient with Child's class B cirrhosis underwent orthotopic liver transplantation at week 13 after dramatic increases in liver tests and clinical worsening. The patient subsequently cleared HBeAg and HBsAg from serum posttransplantation. In conclusion, prolonged therapy with lamivudine resulted in improved serum biochemical values and loss of HBV DNA in patients with decompensated cirrhosis. Clinical improvements, reflected in Child-Pugh classification and functional status, may also occur, particularly among those with Child's class C disease initially. [source] Prenatal diagnosis of Niemann,Pick diseases types A, B and CPRENATAL DIAGNOSIS, Issue 7 2002Marie T. Vanier Abstract Prenatal diagnosis of Niemann,Pick disease types A and B is routinely accomplished by sphingomyelinase assay. For Niemann,Pick type C disease, demonstration of an abnormal intracellular cholesterol trafficking is a complex procedure, and mutational analysis (NPC1 or NPC2/HE1 gene), whenever feasible, represents a major advance. Copyright © 2002 John Wiley & Sons, Ltd. [source] Safety and efficacy of meningococcal c vaccination in juvenile idiopathic arthritisARTHRITIS & RHEUMATISM, Issue 2 2007Evelien Zonneveld-Huijssoon Objective To determine whether vaccinations aggravate the course of autoimmune diseases such as juvenile idiopathic arthritis (JIA) and whether the immune response to vaccinations may be hampered by immunosuppressive therapy for the underlying disease. Methods In this multicenter cohort study, 234 patients with JIA (ages 1,19 years) were vaccinated with meningococcal serogroup C (MenC) conjugate to protect against serogroup C disease (caused by Neisseria meningitidis). Patients were followed up for disease activity for 1 year, from 6 months before until 6 months after vaccination. IgG antibody titers against MenC polysaccharide and the tetanus carrier protein were determined by enzyme-linked immunosorbent assay and toxin binding inhibition assay, respectively. A serum bactericidal assay was performed to determine the function of the anti-MenC antibodies. Results No change in values for any of the 6 components of the core set criteria for juvenile arthritis disease activity was seen after MenC vaccination. Moreover, no increase in the frequency of disease relapse was detected. Mean anti-MenC IgG concentrations in JIA patients rose significantly within 6,12 weeks after vaccination. Of 157 patients tested, 153 were able to mount anti-MenC IgG serum levels >2 ,g/ml, including patients receiving highly immunosuppressive medication. The 4 patients with a lower anti-MenC antibody response displayed sufficient bactericidal activity despite receiving highly immunosuppressive medication. Conclusion The MenC conjugate vaccine does not aggravate JIA disease activity or increase relapse frequency and results in adequate antibody levels, even in patients receiving highly immunosuppressive medication. Therefore, patients with JIA can be vaccinated safely and effectively with the MenC conjugate. [source] Induction of potent antitumour natural-killer cells from peripheral blood of patients with advanced prostate cancerBJU INTERNATIONAL, Issue 9 2003T. Oikawa In this section there are four papers on a variety of topics. The subject of antitumour natural killer cells is addressed in patients with advanced prostate cancer. In another study, the authors describe their work into the effect of oestrogen and testosterone on the urethral seam of the developing male mouse genital tubercle. Another group of authors studied ion-channel currents of smooth muscle cells isolated from the prostate of the guinea pig, and the final paper describes how a novel pyrrole derivative, NS-8, suppresses the rat micturition reflex by inhibiting afferent pelvic nerve activity. OBJECTIVE To examine whether antitumour natural-killer (NK) cells can be induced from peripheral blood mononuclear cells (PBMCs) of patients with advanced prostate cancer, as cell therapy using antitumour immune cells is a promising candidate treatment but such patients generally have a suppressed immune response against cancer cells. PATIENTS AND METHODS PBMCs were obtained from 10 patients (four with stage D2 and six with stage B or C disease). For the NK cell expansion, PBMCs were co-cultured with irradiated HFWT cells, a cell line originating from Wilms' tumour, in RHAM , culture medium supplemented with 5% autologous plasma and interleukin-2 (200 U/mL) for 2 weeks. RESULTS When PBMCs were co-cultured with HFWT cells, lymphocytes from all patients had a 20- to 130-fold expansion after 2 weeks of culture. The CD16+ CD56+ cells constituted >,70% of the proliferated lymphocyte population. The induced NK cells had significantly greater cytotoxicity against a prostate cancer cell line (PC-3) than lymphocytes cultured with no HFWT cells. There was no significant difference in growth and phenotypes of lymphocytes and the induced NK cell activity between patients with stage D2, B or C. CONCLUSION NK cells with potent cytotoxic activity against prostate cancer cell lines from patients with advanced prostate cancer were selectively expanded. Further investigation is needed to determine whether this approach could be a candidate for cell therapy for advanced prostate cancer. [source] The impact of surgeon and pathologist on lymph node retrieval in colorectal cancer and its impact on survival for patients with Dukes' stage B diseaseCOLORECTAL DISEASE, Issue 2 2008M. D. Evans Abstract Objective, An adequate lymph node harvest is necessary for accurate Dukes' stage discrimination in colorectal cancer. The aim of this study is to identify the effect of variables, including the individual surgeon and pathologist, on lymph node harvest in a single institution. Method, Three hundred and eighty one consecutive patients had resection for colorectal cancer, in a single unit. Factors influencing lymph node retrieval, including individual surgeon and reporting pathologist, were subjected to uni- and multivariate analysis. Actuarial survival of all patients with Dukes' stage B and C disease was then calculated and survival compared between Dukes' stage B and C at differing levels of lymph node harvest. Results, The unit median lymph node harvest was 13 nodes/patient (95% CI 13.1,14.5). There was no difference in lymph node harvest between specialist colorectal surgeons and the pooled results of four nonspecialist consultant surgeons. However, there was a significant difference between reporting pathologists (P < 0.001). On univariate analysis, operation type, operative urgency, Dukes' stage, T-stage, reporting pathologist and use of neoadjuvant therapy in rectal cancer, were found to significantly affect lymph node retrieval. On multivariate analysis, operation type, T-stage, reporting pathologist and neoadjuvant therapy in rectal cancer remained significant variables. Patients with one or more lymph node metastasis had greater nodal harvests than those without (median 15 vs 12 P = 0.02). Survival of patients with Dukes' stage B disease was found to improve as lymph node harvest increased. Conclusion, Overall lymph node harvest, in this unit, varied according to the reporting pathologist but not operating surgeon. As lymph node harvest increased to 15 per patient, the probability of identifying a metastatic node increased. [source] | |||||||||||||