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1.
To examine the role of complement in certain autoimmune neuromuscular diseases, we used an in-vitro quantitative complement uptake assay that allows measurement of the capacity of patients' sera to deposit fragments of the third complement component onto sensitized targets. C3 uptake was significantly higher in patients with active dermatomyositis, Guillain-Barré syndrome and myasthenia gravis, compared to inclusion body myositis and controls. The in-vitro C3 uptake assay supports the role of C3b neoantigen and Membranolytic Attack Complex deposition in the target tissues and may be a useful tool to monitor disease activity in patients with complement-mediated neurological disorders. 相似文献
2.
Aristides Th. Marinos Anastasia J. Tzonou Menelaos E. Karantzas 《Statistics in medicine》1995,14(12):1291-1306
The formulae for some typical epidemiological indices in case-control studies with non-differential misclassification are expressed in terms of two groups (α, β) and (γ, δ) of misclassification probabilities of exposure E and confounder C, respectively, and the initially estimated frequencies. The parameters α and β denote the probability that subjects exposed to E are classified as non-exposed and the probability that non-exposed ones will be classified as exposed, respectively. Similarly, δ and γ stand for the probability that those who have been exposed to C will be classified as non-exposed and the probability that non-exposed subjects are classified as exposed, respectively. The non-negativeness of the expressions for the ‘true’ frequencies in terms of the measured ones and the misclassification probabilities leads to the construction of feasibility regions for α, β, γ and δ. For a number of ‘acceptable’ 4-tuples (α, β, γ, δ), all of which lie inside these feasibility regions, a sequence of feasible values for an epidemiological index is determined, after employing a systematic procedure by means of a ‘searching net’ with increments Δα, Δβ, Δγ, Δδ. The procedure serves to determine the characteristics of the (experimental) cumulative distribution function for any selected epidemiological index. The final stage in exploiting the structure of feasibility regions for α, β, γ and δ is to use the cumulative distribution function to calculate quantiles for the index associated with prescribed probabilities. 相似文献
3.
Abnormal skeletal and cardiac muscle mitochondria induced by zidovudine (AZT) in human muscle in vitro and in an animal model. 总被引:1,自引:0,他引:1
L Lamperth M C Dalakas F Dagani J Anderson R Ferrari 《Laboratory investigation; a journal of technical methods and pathology》1991,65(6):742-751
To examine the mechanism of mitochondrial myocytotoxicity caused by long-term administration of zidovudine (AZT) in human immunodeficiency virus-positive patients, we examined the effect of AZT in vitro on human muscle in tissue culture and in vivo in rats treated with daily intraperitoneal injections of AZT at doses equivalent to the total daily dose used in acquired immunodeficiency syndrome patients. After 19 days, the AZT-treated myotubes in tissue culture exhibited abnormal mitochondria characterized by proliferation (mean +/- SD, 27.5 +/- 8 mitochondria/16 microns2 surface area, compared with 12.8 +/- 4 in the control cultures (p less than 0.001], enlarged size, abnormal cristae and electron-dense deposits in their matrix. The changes were partially reversible after AZT withdrawal. Rats treated with AZT developed weight loss, 100-fold elevation of creatine kinase, and increased serum lactate and glucose. In tissues, AZT had its highest concentration in the skeletal muscle and the heart. Skeletal and heart muscles from the treated animals, but not the controls, showed enlarged mitochondria with disorganized or absent cristae and electron-dense deposits in their matrix. Study of the mitochondrial functions assessed by evaluating stimulated oxygen consumption rate, enzymatic activities of electron transport chain and coupling state of oxidative phosphorylation (respiratory control ratio) revealed a decrease in rotenone-sensitive NADH cytochrome C reductase (complex I + III) and an uncoupling effect demonstrated by decreased respiratory control ratio. We conclude that AZT, a DNA chain terminator, is a muscle mitochondrial toxin that affects the oxidation-phosphorylation coupling and the activity of complex I and III of the mitochondrial respiratory chain. 相似文献
4.
Missense mutations in the beta-myosin heavy-chain gene cause central core disease in hypertrophic cardiomyopathy. 总被引:9,自引:2,他引:7
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L Fananapazir M C Dalakas F Cyran G Cohn N D Epstein 《Proceedings of the National Academy of Sciences of the United States of America》1993,90(9):3993-3997
Hypertrophic cardiomyopathy (HCM) is an important cause of sudden death in apparently healthy young individuals. In less than half of kindreds with HCM, the disease is linked to the beta-myosin heavy-chain gene locus (MYH7). We have recently described two missense MYH7 gene mutations [Arg-403 to Gln (R403Q) and Leu-908 to Val (L908V)] and found that the mutant message is present in skeletal muscle soleus) and that the mutant beta-myosin obtained from soleus muscle has abnormal in vitro motility activity. Having identified a second kindred with the R403Q mutation, and 3 other kindreds with two additional mutations (G741R and G256E), we performed histochemical analysis of soleus muscle biopsies from 25 HCM patients with one of these four mutations. Light microscopic examination of the NADH-stained biopsies revealed the presence of central core disease (CCD) of skeletal muscle, a rare autosomal dominant nonprogressive myopathy characterized by a predominance of type I "slow" fibers and an absence of mitochondria in the center of many type I fibers. CCD was present in 10 of 13 patients with the L908V mutation, 5 of 8 patients with the R403Q mutation, 1 of 3 patients with the G741R mutation, and 1 patient with the G256E mutation. Mild-to-moderate myopathic changes with muscle fiber hypertrophy were present in 16 patients. Notably, CCD was present in 2 adults and 3 children with the L908V mutation who did not have cardiac hypertrophy. In contrast, soleus muscle samples from 5 patients from 4 kindreds in which HCM was not linked to the MYH7 locus showed no myopathy or CCD. Soleus muscle biopsies from 5 control subjects also showed normal histology. This work demonstrates that (i) MYH7-associated HCM is often a disease of striated muscle but with predominant cardiac involvement and (ii) a subset of HCM patients with MYH7 gene missense mutations have CCD. 相似文献
5.
Phototherapy as a first‐line treatment for early‐stage mycosis fungoides: The results of a large retrospective analysis
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6.
Change of appetite in patients with functional digestive disorder. Association with psychological disorders: A cross‐sectional study
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Marinos Fysekidis Michel Bouchoucha Florence Mary Gheorghe Airinei Cyriaque Bon Robert Benamouzig 《Journal of gastroenterology and hepatology》2018,33(1):195-202
Background and Aims
Changes in appetite are a frequent complaint in patients with functional gastrointestinal disorders (FGIDs). The aims of this study are to evaluate whether the changes in appetite are associated with specific FGIDs and to explore associations of these changes with symptoms of anxiety or depression.Methods
This study included 1009 consecutive FGID patients (71% female), aged 48.9 years who all filled out a Rome III questionnaire for the evaluation of FGIDs, submitted to a psychological evaluation of symptoms of anxiety, and completed the Beck Depression Inventory questionnaire. The patients were classified according to their appetite change using a 7‐point grading scale and split into three groups: those with appetite loss, those with no change in appetite, and those with increased appetite.Results
Among the 1009, 496 patients (49%) reported a change in appetite, of which 332 (33%) patients reported a decrease in appetite and 164 (16%) patients reported an increase in appetite. Appetite was not affected in 51% of patients. Changes in appetite depended on gender, body mass index and psychometric evaluation scores. Increased appetite did not have specific FGIDs associations, while decreased appetite was associated with esophageal, gastroduodenal, bowel, and anorectal symptoms. The presence of depressive symptoms was also a predictor for the majority of FGIDs in decreased appetite, while anxiety trait was significant for globus and dysphagia.Conclusions
Decreased appetite was associated with FGIDs, especially in the presence of depressive symptoms. A reduced appetite would help to predict psychological disorders associated with FGIDs.Financial disclosure
None declared.Legal registration
This study was a registered study in the French National Drug Agency (ANSM, Agence Nationale de Securité du Medicamentet des produits de santé, Study Number 2016‐A01120‐51).Competing interests
Michel Bouchoucha, Marinos Fysekidis, Florence Mary, Gheorghe Airinei, Cyriaque Bon, and Robert Benamouzig have no competitive interests. 相似文献7.
8.
David Mutimer Nicolai Naoumov Pieter Honkoop George Marinos Monz Ahmed Robert de Man Penny McPhillips Mark Johnson Roger Williams Elwyn Elias Solko Schalm 《Journal of hepatology》1998,28(6):923-929
Background/Aims: Alpha-interferon achieves seroconversion in about one third of naive patients. Attempts to achieve seroconversion in patients who have previously failed alpha-interferon have proved disappointing. Combination chemotherapy (alpha-interferon with a nucleoside analogue) might provide a treatment alternative for these patients. We have undertaken a phase 2 study in 20 patients who had previously failed at least one course of alpha-interferon. The study was designed to assess the safety, tolerability and efficacy of the combination.Methods: All patients were treated for 16 weeks with alpha-interferon in combination with 12 or 16 weeks of Lamivudine (3′TC). Patients were followed for 16 weeks post-treatment. Pharmacokinetic studies were performed to identify/exclude significant pharmacokinetic drug interaction.Results: The combination was well tolerated, and side-effects of the combination were indistinguishable from the recognised side-effects of alpha-interferon. Pharmacokinetic studies performed on days 1 and 29 did not show any significant interaction. All patients achieved HBV DNA clearance during treatment, but 19 relapsed at the end of treatment. HBeAg/anti-HBe seroconversion was observed for four patients, but was sustained for a single patient (who also had sustained DNA clearance).Conclusions: Combination therapy with alpha-interferon and lamivudine given for 16 weeks appears safe and is well tolerated. However, for this group of patients who had previously failed interferon monotheraphy appears disappointing, and other treatment strategies should be investigated. 相似文献
9.
Freeman AJ Pan Y Harvey CE Post JJ Law MG White PA Rawlinson WD Lloyd AR Marinos G Ffrench RA 《Journal of hepatology》2003,38(3):349-356
BACKGROUND/AIMS: The role of cytotoxic T lymphocytes (CTL) in limiting viral replication and producing hepatocellular injury in patients with chronic hepatitis C virus (HCV) infection is controversial. METHODS: Intrahepatic and peripheral blood HCV-specific CTL activity against the entire HCV polyprotein was assessed in 26 patients. CTL responses were assessed after effector lymphocytes were re-stimulated for 6 days in vitro using HCV-vaccinia virus-infected autologous cells expressing HCV antigens. Serum and hepatic viral loads were measured and immunohistochemistry for CD3 and CD8 was performed to localise and enumerate effector cells in liver. RESULTS: A positive CTL response was detected in 39/52 (75%) of assays conducted with intrahepatic mononuclear cells and 21/52 (40%) of peripheral blood assays (P<0.001). The presence of an intrahepatic CTL response was associated with low hepatic viral load (P=0.004). Hepatic lobular infiltration by CD8(+)T cells correlated weakly with serum alanine aminotransferase levels (r=0.42, P=0.04) and no relationship was demonstrated between CTL activity and histological evidence of liver damage. CONCLUSIONS: HCV-specific CTL activity is found more commonly in liver than in blood. An inverse relationship between CTL responses and viral load supports the hypothesis that HCV-specific CTL limit viral replication in patients with chronic HCV infection. 相似文献
10.
R L Leff S H Burgess F W Miller L A Love I N Targoff M C Dalakas M M Joffe P H Plotz 《Arthritis and rheumatism》1991,34(11):1391-1396
In idiopathic inflammatory myopathy (IIM; or, polymyositis/dermatomyositis), the myositis-specific autoantibodies anti-Jo-1 and anti-signal recognition particle (anti-SRP), appear to define clinically and immunogenetically distinct groups of patients. We show here that the month during which the onset of weakness occurs is not random in patients with anti-Jo-1 auto-antibodies (average month April, P less than 0.02) and in those with anti-SRP autoantibodies (average month November, P less than 0.02); both groups of patients also experience rapid onset of disease. By contrast, patients classified into the traditional categories of polymyositis and dermatomyositis do not have recognizable seasonal patterns and do not differ in the rate of onset of disease. These findings suggest that searches for seasonal patterns in the onset of autoimmune disorders characterized by disease-specific autoantibodies may provide useful clues to etiology. 相似文献