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991.
PURPOSE OF REVIEW: Multiple sclerosis is a major cause of neurological disability in Western societies. The most important reason for the limited success obtained in the treatment and prevention so far is most likely related to the limited knowledge about its cause and pathogenesis. This paper discusses recent progress and controversies in the understanding of the pathogenesis and cause of multiple sclerosis. RECENT FINDINGS: Both T helper cells type 1 (Th1 cells), Th17 cells, cytotoxic T cells, B cells and regulatory T cells are involved in the inflammatory process. Axonal loss seems to be driven by inflammation during the early stages of disease but may become independent of inflammation at later stages. The target antigen of the immune response has not been identified. Weak genetic association has been established in two cytokine receptors, whereas increasing female: male ratio support the importance of environmental risk factors. A substantial proportion of intrathecal B cells are infected with Epstein-Barr virus. SUMMARY: Multiple sclerosis is a complex disease and calls for integrated efforts from immunology, epidemiology, neuroscience and genetics. In particular, the immunological implications of environmental risk factors such as vitamin D desufficiency, smoking and Epstein-Barr virus infection need to be explored. 相似文献
992.
Hepatitis C virus-associated hypobetalipoproteinemia is correlated with plasma viral load,steatosis, and liver fibrosis 总被引:3,自引:0,他引:3
Petit JM Benichou M Duvillard L Jooste V Bour JB Minello A Verges B Brun JM Gambert P Hillon P 《The American journal of gastroenterology》2003,98(5):1150-1154
OBJECTIVES: A relationship between chronic hepatitis C virus (HCV) infection and lipid metabolism has recently been suggested. The aim of this study was to determine the correlation between lipid profile and virology, histologic lesions, and response to alpha interferon therapy in noncirrhotic, nondiabetic patients with hepatitis C. METHODS: A total of 109 consecutive untreated chronic hepatitis C patients were studied to assess the following: 1) the effects of HCV genotype, viral load, steatosis, hepatic fibrosis, and body mass index (BMI) on lipid profile; and 2) whether lipid parameters could predict response to antiviral therapy. RESULTS: The control group showed a significantly higher apolipoprotein B (apoB) concentration compared with patients with chronic hepatitis C. Hypobetalipoproteinemia (apo B <0.7 g/L) was found in 27 (24.7%) chronic HCV patients and in five (5.3%) control subjects (p = 0.0002). Levels of apo B were negatively correlated with steatosis and HCV viral load (r = -0.22; p = 0.03). This last correlation was strong for non-1 genotype and genotype 3 (r = -0.48; p = 0.0005, and r = -0.47; p = 0.007, respectively) but was not found in genotype 1. In multivariate analysis, low apo B concentration was significantly associated with fibrosis grade 2 or 3 versus grade 0 or 1 (p < 0.001), steatosis >5% (p < 0.001), low body mass index (p < 0.001), and high HCV viral load (p < 0.014). No correlation was found in the 76 treated patients between apo B and response to interferon therapy. CONCLUSIONS: In chronic HCV patients, hypobetalipoproteinemia occurs already in the early stages of HCV infection before the development of liver cirrhosis. The correlation between apo B levels and HCV viral load seems to confirm the interaction between hepatitis C infection and beta-lipoprotein metabolism. 相似文献
993.
Colbert LH Visser M Simonsick EM Tracy RP Newman AB Kritchevsky SB Pahor M Taaffe DR Brach J Rubin S Harris TB 《Journal of the American Geriatrics Society》2004,52(7):1098-1104
OBJECTIVES: To examine the association between physical activity and inflammatory markers, with consideration for body fatness and antioxidant use. DESIGN: Cross-sectional study, using baseline data from the Health, Aging and Body Composition Study. SETTING: Metropolitan areas surrounding Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Black and white, well-functioning men and women (N=3,075), aged 70 to 79. MEASUREMENTS: Interviewer-administered questionnaires of previous-week household, walking, exercise, and occupational/volunteer physical activities. Analysis of covariance was used to examine the association between activity level and serum C-reactive protein (CRP), interleukin-6 (IL-6), and plasma tumor necrosis factor alpha (TNFalpha) with covariate adjustment. Antioxidant supplement use (multivitamin, vitamins E or C, beta carotene) was evaluated as an effect modifier of the association. RESULTS: Higher levels of exercise were associated with lower levels of CRP (P<.01), IL-6 (P<.001), and TNFalpha (P=.02) (e.g., CRP=1.95 mg/L for no exercise and 1.72 for >180 min/wk). Adjustment for body fatness attenuated the associations somewhat. Use of antioxidant supplements modified the CRP (P(interaction)=.01) and IL-6 (P(interaction)=.08) associations such that concentrations were low in those taking supplements (e.g., CRP=1.79-1.84 across exercise levels) and higher in nonsupplement users who did no exercise (2.03) than in those who did the most (1.72). Among nonexercisers, higher levels of other physical activity were related to lower levels of CRP (P<.01) and IL-6 (P=.02) but not TNFalpha (P=.36), even after accounting for body fat. CONCLUSION: Inflammatory markers are lower in older adults with higher levels of exercise and nonexercise activity and in antioxidant supplement users regardless of exercise level. 相似文献
994.
Holmberg SD Moorman AC Williamson JM Tong TC Ward DJ Wood KC Greenberg AE Janssen RS;HIV Outpatient Study 《Lancet》2002,360(9347):1747-1748
Protease inhibitors for treatment of HIV-1 have been linked with increased risk of hyperlipidaemia and hyperglycaemia. In a cohort of 5672 outpatients with HIV-1 seen at nine US HIV clinics between January, 1993, and January, 2002, the frequency of myocardial infarctions increased after the introduction of protease inhibitors in 1996 (test for trend, p=0.0125). We noted that 19 of 3247 patients taking, but only two of 2425 who did not take, protease inhibitors had a myocardial infarction (odds ratio 7.1, 95% CI 1.6-44.3; Cox proportional hazards model-adjusted for smoking, sex, age, diabetes, hyperlipidaemia, and hypertension-hazard ratio 6.5, 0.9-47.8). Our findings suggest that, although infrequent, use of protease inhibitors is associated with increased risk of myocardial infarction in patients with HIV-1. 相似文献
995.
The genetics of type 2 diabetes 总被引:7,自引:0,他引:7
996.
Jonathan G. Amatruda MD Ronit Katz DPhil Carmen A. Peralta MD MAS Michelle M. Estrella MD MHS Harini Sarathy MBBS MHS Linda F. Fried MD MPH Anne B. Newman MD MPH Chirag R. Parikh MBBS PhD Joachim H. Ix MD MAS Mark J. Sarnak MD MS Michael G. Shlipak MD MPH for the Health ABC Study 《Journal of the American Geriatrics Society》2021,69(3):726-734
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Brandon P. Verdoorn MD Tamara K. Evans BS Gregory J. Hanson MD Yi Zhu PhD Larissa G. P. Langhi Prata PhD Robert J. Pignolo MD PhD Elizabeth J. Atkinson MS Erin O. Wissler-Gerdes MA George A. Kuchel MD Joan B. Mannick MD Stephen B. Kritchevsky PhD Sundeep Khosla MD Stacey A. Rizza MD Jeremy D. Walston MD Nicolas Musi MD Lewis A. Lipsitz MD Douglas P. Kiel MD Raymond Yung MB ChB Nathan K. LeBrasseur PhD Ravinder J. Singh PhD Teresa McCarthy MD MS Michael A. Puskarich MD Laura J. Niedernhofer MD PhD Paul D. Robbins PhD Matthew Sorenson JD MA Tamara Tchkonia PhD James L. Kirkland MD PhD 《Journal of the American Geriatrics Society》2021,69(11):3023-3033
The burden of senescent cells (SnCs), which do not divide but are metabolically active and resistant to death by apoptosis, is increased in older adults and those with chronic diseases. These individuals are also at the greatest risk for morbidity and mortality from SARS-CoV-2 infection. SARS-CoV-2 complications include cytokine storm and multiorgan failure mediated by the same factors as often produced by SnCs through their senescence-associated secretory phenotype (SASP). The SASP can be amplified by infection-related pathogen-associated molecular profile factors. Senolytic agents, such as Fisetin, selectively eliminate SnCs and delay, prevent, or alleviate multiple disorders in aged experimental animals and animal models of human chronic diseases, including obesity, diabetes, and respiratory diseases. Senolytics are now in clinical trials for multiple conditions linked to SnCs, including frailty; obesity/diabetes; osteoporosis; and cardiovascular, kidney, and lung diseases, which are also risk factors for SARS-CoV-2 morbidity and mortality. A clinical trial is underway to test if senolytics decrease SARS-CoV-2 progression and morbidity in hospitalized older adults. We describe here a National Institutes of Health-funded, multicenter, placebo-controlled clinical trial of Fisetin for older adult skilled nursing facility (SNF) residents who have been, or become, SARS-CoV-2 rtPCR-positive, including the rationale for targeting fundamental aging mechanisms in such patients. We consider logistic challenges of conducting trials in long-term care settings in the SARS-CoV-2 era, including restricted access, consent procedures, methods for obtaining biospecimens and clinical data, staffing, investigational product administration issues, and potential solutions for these challenges. We propose developing a national network of SNFs engaged in interventional clinical trials. 相似文献