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1.
Sundaramurthy Srilekha SelvaKumar Ambika Ching Jared Dharani Vidhya Sarangapani Sripriya Yu-Wai-Man Patrick 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2021,259(9):2461-2472
Graefe's Archive for Clinical and Experimental Ophthalmology - Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial DNA (mtDNA) disorder with the majority of... 相似文献
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The safety and efficacy of leflunomide in combination with infliximab in rheumatoid arthritis 总被引:8,自引:0,他引:8
Hansen KE Cush J Singhal A Cooley DA Cohen S Patel SR Genovese M Sundaramurthy S Schiff M 《Arthritis and rheumatism》2004,51(2):228-232
OBJECTIVE: To report the safety and efficacy of leflunomide (LEF) in combination with infliximab (INF) for the treatment of rheumatoid arthritis. METHODS: In an open, multicenter, retrospective study, data were collected on the safety and efficacy of LEF and INF. RESULTS: Eighty-eight patients received the combination of LEF and INF for an average of 6.6 months and a total exposure of 581 patient-months. The mean duration of LEF was 17 +/- 9 months (range 3-32 months; median 18.5 months) with an average of 4.8 INF infusions per patient. In all but 3 subjects, LEF was used initially and INF was added later. Infusion reactions occurred in 3 patients (0.7% of all infusions). A total of 34% of subjects experienced adverse events and in 6 (6.8% of the group) these were deemed serious. Ten infections occurred when patients were taking the combination; 9 patients recovered fully and 1 died of bacterial pneumonia. A lifetime smoker developed lung cancer and another patient was found to have colon cancer. CONCLUSIONS: The adverse events noted within the combination therapy group were in keeping with the known risks of each drug when used individually. Limited data were available on efficacy, but a general improvement in disease control was noted with the combination of drugs, which for most patients involved the addition of INF to previous use of LEF. 相似文献
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Shoib S. Siddiqui Chirag Dhar Venkatasubramaniam Sundaramurthy Aniruddha Sasmal Hai Yu Esther Bandala-Sanchez Miaomiao Li Xiaoxiao Zhang Xi Chen Leonard C. Harrison Ding Xu Ajit Varki 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(10)
Blood pH is tightly maintained between 7.35 and 7.45, and acidosis (pH <7.3) indicates poor prognosis in sepsis, wherein lactic acid from anoxic tissues overwhelms the buffering capacity of blood. Poor sepsis prognosis is also associated with low zinc levels and the release of High mobility group box 1 (HMGB1) from activated and/or necrotic cells. HMGB1 added to whole blood at physiological pH did not bind leukocyte receptors, but lowering pH with lactic acid to mimic sepsis conditions allowed binding, implying the presence of natural inhibitor(s) preventing binding at normal pH. Testing micromolar concentrations of divalent cations showed that zinc supported the robust binding of sialylated glycoproteins with HMGB1. Further characterizing HMGB1 as a sialic acid-binding lectin, we found that optimal binding takes place at normal blood pH and is markedly reduced when pH is adjusted with lactic acid to levels found in sepsis. Glycan array studies confirmed the binding of HMGB1 to sialylated glycan sequences typically found on plasma glycoproteins, with binding again being dependent on zinc and normal blood pH. Thus, HMGB1-mediated hyperactivation of innate immunity in sepsis requires acidosis, and micromolar zinc concentrations are protective. We suggest that the potent inflammatory effects of HMGB1 are kept in check via sequestration by plasma sialoglycoproteins at physiological pH and triggered when pH and zinc levels fall in late stages of sepsis. Current clinical trials independently studying zinc supplementation, HMGB1 inhibition, or pH normalization may be more successful if these approaches are combined and perhaps supplemented by infusions of heavily sialylated molecules.The pH of body fluids in healthy individuals spans a very broad range in different tissue types and organs, ranging from pH 1.5 (stomach contents) to 8.0 (urine). Human cells in tissue culture can also tolerate a wide range of pH values. In contrast, blood pH is tightly regulated between 7.35 and 7.45 (1), and departure out of this range (acidosis or alkalosis) can be very detrimental. For example, in the recent COVID-19 pandemic, 30% of nonsurvivors had acidosis, compared to 1% among survivors (2). Acidosis in sepsis is partly due to lactic acid release from anoxic tissues, which overwhelms the buffering capacity of circulating blood (3). A “cytokine storm” of proinflammatory mediators in sepsis triggers a cascade of destructive outcomes such as multiple organ failure (4–8) as currently seen in severe cases of COVID-19 infection (9). The mechanisms underlying lethality associated with low blood pH are not clear but include low zinc levels and release from apoptotic or necrotic cells of High mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) defined as one of the late mediators of sepsis, further up-regulating many other proinflammatory cytokines (10–12). Importantly, a recent study indicates that HMGB1 levels are strongly associated with mortality in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (13). Here we show that sialylated plasma glycoproteins bind HMGB1 to suppress its ability to promote inflammatory responses in a zinc- and pH-dependent manner. Besides providing an explanation for the very tight regulation of blood pH, these findings provide an avenue for developing a new therapeutic strategy for treating sepsis. 相似文献
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Ward MM Sundaramurthy S Lotstein D Bush TM Neuwelt CM Street RL 《Arthritis and rheumatism》2003,49(6):810-818
OBJECTIVE: To examine associations between active patient-physician communication and measures of morbidity in patients with systemic lupus erythematosus (SLE). METHODS: Audiotapes of routine visits between 79 women with SLE and their rheumatologists were coded for active patient participation and the degree of patient-centered communication of the physician, using a validated coding scheme. Measures of SLE activity, functional disability, and permanent organ damage were recorded at the same visit. Permanent organ damage was reassessed in 68 patients after a median of 4.7 years. RESULTS: Patients who participated more actively in their visits had less permanent organ damage, as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, and tended to accrue less organ damage over time. There were no associations between either active patient participation or physicians' patient-centered communication scores and measures of SLE activity or functional disability. CONCLUSIONS: Patients with SLE who participated more actively in their visits had less permanent organ damage, suggesting that involving patients more in their care may decrease morbidity. 相似文献
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Benjamin R. Poh Senthilkumar R. Sundaramurthy Naseem Mirbagheri 《Journal of gastrointestinal surgery》2014,18(7):1377-1378
A case of small bowel obstruction secondary to a left paraduodenal hernia is illustrated together with its radiological features and intra-operative appearance. Paraduodenal hernias are rare congenital causes of small bowel obstruction, and various approaches to surgical treatment are available including conventional open and minimally invasive laparoscopic techniques. This case presents one possible option for surgical management and briefly reviews the literature for the various surgical techniques and strategies available to the surgeon when faced with a left paraduodenal hernia. 相似文献
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Anorexia nervosa (AN) is an enigmatic syndrome affecting approximately 0.1% of the at risk population in the UK which equates to approximately 70000 sufferers. Data from a number of studies have demonstrated the heritability of this disorder, however it is only in the last few years that studies have begun to determine the involvement of particular candidate genes in this genetic predisposition. In the current study we have used classical case-control association analysis to determine whether two highly polymorphic microsatellite markers, located within a 3-cM region of the UCP-2/UCP-3 locus, show involvement of this region of the human genome in the predisposition to AN. Analysis of a cohort of 170 female Caucasian anorexia nervosa sufferers and 150 normal female controls shows evidence of association with the marker D11S911 but not D11S916. Allele 13 of the marker D11S911 is significantly over represented in the anorexia nervosa population suggesting that a mutation in linkage disequilibrium with this locus may form part of the genetic component of AN. Further work is now required to try to reproduce these data in a second independent cohort and to further characterise this region of the human genome. 相似文献
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Anchu Rachel Thomas Natanasabapathy VelmuruganSurendran Smita MDS Sundaramurthy Jothilatha MDS 《Journal of endodontics》2014