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Leishmania donovani suppresses activated protein 1 and NF-kappaB activation in host macrophages via ceramide generation: involvement of extracellular signal-regulated kinase 下载免费PDF全文
Ghosh S Bhattacharyya S Sirkar M Sa GS Das T Majumdar D Roy S Majumdar S 《Infection and immunity》2002,70(12):6828-6838
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Sukhwinder S Lakhman Debashis Ghosh Javier G Blanco 《Drug metabolism and disposition》2005,33(2):254-257
Human carbonyl reductase (CBR) activity accounts for a significant fraction of the metabolism of endogenous and xenobiotic carbonyl compounds. It is possible that genetic polymorphisms in CBR1 and CBR3 are key for the wide interindividual variability in the disposition of CBR drug substrates. We pinpointed a single nucleotide polymorphism in CBR3 (CBR3 V244M) that encodes for a V244 to M244 change. Blacks showed a higher frequency of the M244 allele (q = 0.51, n = 49) than did whites (q = 0.31, n = 70; p = 0.003). In addition, DNA variation panels from 10 ethnic groups presented a wide range of CBR3 V244M genotype distributions. Kinetic experiments with the recombinant CBR3 protein variants and menadione revealed that CBR3 M244 has significantly higher V(max) than does CBR3 V244 (V(max) CBR3 M244 = 40.6 +/- 1.3 micromol/min x mg versus V(max) CBR3 V244 = 19.6 +/- 2.0 micromol/min x mg, p = 0.002). In contrast, both isoforms presented similar K(m) values (K(m) CBR3 M244 = 22.9 +/- 2.9 microM versus K(m) CBR3 V244 = 24.6 +/- 3.2 microM, p = 0.43). Assays with NADP(H) demonstrated a higher V(maxNADP(H)) (1.6-fold) and increased catalytic efficiency (V(maxNADP(H))/K(mNADP(H))) for CBR3 M244 compared with CBR3 V244 (p = 0.013). Comparative three-dimensional analyses based on the structure of the homologous porcine carbonyl reductase suggested that the V244M substitution is positioned in a region critical for interactions with the NADP(H) cofactor. These studies demonstrate that the common CBR3 V244M polymorphism encodes for CBR3 isoforms with distinctive enzymatic properties. 相似文献
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Jayati K. BASU Eckhart J. BUCHMANN Debashis BASU 《The Australian & New Zealand journal of obstetrics & gynaecology》2009,49(2):158-161
Background: Management of the second stage of labour is dictated by arbitrary time limits rather than true measures of progress. No partogram is available for second stage of labour.
Objectives: To evaluate a partogram designed for use for the second stage of labour.
Methods: This prospective cross-sectional analytical study included low-risk pregnant women with singleton fetuses with vertex presentations at term. From onset of the second stage, vaginal examinations were performed every 30 min until delivery. A scoring system developed by Sizer et al . was used based on station and position of fetal head. Scores were plotted on a second stage partogram and used to predict labour outcomes, such as duration of second stage and mode of delivery.
Results: Of 79 women examined, 73 had spontaneous vaginal delivery. Of the remaining six, four required oxytocin infusion and other two required vacuum extraction. The median durations of the second stage of labour for primigravidas ( n = 34) and multigravidas ( n = 45) were 35 and 25 min, respectively. The median Sizer's partogram score at the onset of second stage was 4. Multiple regression analysis showed that the partogram score ( r2 = 0.27) and gravidity ( r 2 = 0.10) were independent predictors of duration of the second stage. There was a significant association between second stage progress plotted to the right of the partogram line and non-spontaneous delivery ( P = 0.01).
Conclusion: The second stage partogram score at onset can predict the duration of second stage. Poor progress plotted on the partogram is associated with non-spontaneous delivery. 相似文献
Objectives: To evaluate a partogram designed for use for the second stage of labour.
Methods: This prospective cross-sectional analytical study included low-risk pregnant women with singleton fetuses with vertex presentations at term. From onset of the second stage, vaginal examinations were performed every 30 min until delivery. A scoring system developed by Sizer et al . was used based on station and position of fetal head. Scores were plotted on a second stage partogram and used to predict labour outcomes, such as duration of second stage and mode of delivery.
Results: Of 79 women examined, 73 had spontaneous vaginal delivery. Of the remaining six, four required oxytocin infusion and other two required vacuum extraction. The median durations of the second stage of labour for primigravidas ( n = 34) and multigravidas ( n = 45) were 35 and 25 min, respectively. The median Sizer's partogram score at the onset of second stage was 4. Multiple regression analysis showed that the partogram score ( r
Conclusion: The second stage partogram score at onset can predict the duration of second stage. Poor progress plotted on the partogram is associated with non-spontaneous delivery. 相似文献
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Bhattacharyya S Ghosh S Dasgupta B Mazumder D Roy S Majumdar S 《The Journal of infectious diseases》2002,185(12):1704-1708
This study explored the role of the proinflammatory chemokines macrophage inflammatory protein (MIP)-1alpha and macrophage chemoattractant protein (MCP)-1 for development of antileishmanial activity. There was substantial inhibition in nitrite generation in Leishmania donovani-infected macrophages. A marked elevation of nitrite generation and induction of inducible nitric oxide (NO) synthase (iNOS) mRNA was found in chemokine-primed parasite-infected macrophages. Tumor necrosis factor-alpha, which is the priming signal for NO production, was also up-regulated under similar experimental conditions. The priming with chemokine inhibited the multiplication of L. donovani amastigotes within the intramacrophageal milieu. The antileishmanial effect of chemokines was almost completely abrogated when the macrophages were preincubated with l-N-monomethyl arginine, the specific inhibitor of iNOS. The results of this investigation suggest that the CC chemokines MIP-1alpha and MCP-1 orchestrate an antileishmanial armamentarium via the induction of an NO-mediated regulatory mechanism to control the intracellular growth and multiplication of the Leishmania protozoan. 相似文献
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Roy D Quiles J Aldama G Sinha M Avanzas P Arroyo-Espliguero R Gaze D Collinson P Carlos Kaski J 《International journal of cardiology》2004,97(2):297-301
BACKGROUND: The diagnosis of myocardial ischemia in patients with acute chest pain at rest but non-diagnostic electrocardiograms (ECG) is problematic. Ischemia Modified Albumin (IMA) is a new biochemical marker of ischemia, which may be useful to characterise acute coronary syndrome (ACS) patients. METHODS: We studied 131 patients (mean age 58.5 years; 95 male) presenting to the emergency department with symptoms suggestive of ACS but with normal or non-diagnostic ECGs. Cardiac troponin T (cTnT) and IMA were measured within 3 h of last chest pain episode. Based on hospital diagnostic test results, patients were classified as having ACS or non-ischemic chest pain (NICP), by two independent cardiologists unaware of IMA results. RESULTS: Mean IMA levels (U/ml) were higher in patients with ACS (98.3+/-11) compared to patients with NICP (85.5+/-15); p<0.0001. IMA levels >93.5 U/ml demonstrated a sensitivity and specificity of 75% for the diagnosis of ACS; area under the receiver operator characteristic curve 0.78 (95% CI: 0.70-0.85). If we applied the manufacturer cutoff point of 85 U/ml, the sensitivity of IMA increased to 90.6% with a specificity of 49.3% (negative predictive value=84.6%). In combination with cTnT (6-12 h) (>0.05 ng/ml), the sensitivity increased to 92.2%. After multivariate analysis, IMA levels >85 U/ml (odds ratio=14.6 [95% CI 4.4-48.4]; p<0.0001), age and prior myocardial infarction were independent predictors of ACS. CONCLUSION: IMA may be a useful biomarker for the identification of ACS in patients presenting with typical acute chest pain but normal or non-diagnostic ECGs. 相似文献
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Willingham SB Volkmer JP Gentles AJ Sahoo D Dalerba P Mitra SS Wang J Contreras-Trujillo H Martin R Cohen JD Lovelace P Scheeren FA Chao MP Weiskopf K Tang C Volkmer AK Naik TJ Storm TA Mosley AR Edris B Schmid SM Sun CK Chua MS Murillo O Rajendran P Cha AC Chin RK Kim D Adorno M Raveh T Tseng D Jaiswal S Enger PØ Steinberg GK Li G So SK Majeti R Harsh GR van de Rijn M Teng NN Sunwoo JB Alizadeh AA Clarke MF Weissman IL 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(17):6662-6667
CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies. 相似文献
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Soumya Sankar Nath Debashis Roy Farrukh Ansari Sundeep T. Pawar 《Indian Journal of Plastic Surgery》2013,46(2):445-452
Anaesthesia related complications in plastic surgeries are fortunately rare, but potentially catastrophic. Maintaining patient safety in the operating room is a major concern of anaesthesiologists, surgeons, hospitals and surgical facilities. Circumventing preventable complications is essential and pressure to avoid these complications in cosmetic surgery is increasing. Key aspects of patient safety in the operating room are outlined, including patient positioning, airway management and issues related to some specific conditions, essential for minimizing post-operative morbidity. Risks associated with extremes of age in the plastic surgery population, may be minimised by a better understanding of the physiologic changes as well as the pre-operative and post-operative considerations in caring for this special group of patients. An understanding of the anaesthesiologist''s concerns during paediatric plastic surgical procedures can facilitate the coordination of efforts between the multiple services involved in the care of these children. Finally, the reader will have a better understanding of the perioperative care of unique populations including the morbidly obese and the elderly. Attention to detail in these aspects of patient safety can help avoid unnecessary complication and significantly improve the patients’ experience and surgical outcome.KEY WORDS: Anaesthesia, complications, plastic, surgery 相似文献