Rapidly progressive crescentic glomerulonephritis and Legionnaires' disease.
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Biomedical subjects
Publications and source records attributed to S Kumar.
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Herpesvirus-like DNA sequences have been identified in a high proportion of both AIDS-associated and classical Kaposi's sarcoma, and in a small percentage of AIDS-associated malignant lymphomas. To determine the extent of involvement of this new agent designated HHV-8 (human herpesvirus type 8) or KSHV (Kaposi's sarcoma-associated herpesvirus) in human malignant lymphomas, we analyzed 24 AIDS-associated lymphoid malignancies and 100 non-AIDS-associated lymphomas by PCR and Southern blot analysis. Three of 24 lymphoid malignancies from patients with AIDS demonstrated HHV-8 sequences by Southern blot and PCR analyses. The fourth was positive by PCR only. None of the non-AIDS-associated lymphomas contained HHV-8 sequences. All three Southern blot positive samples were derived from extranodal regions, two from pleural effusions, and one from a soft tissue mass in the thigh. This latter patient initially presented with a pleural effusion. The fourth PCR positive but Southern blot negative tumor was from a gingival lymphoma in a patient with a history of Kaposi's sarcoma. All tumors positive for HHV-8 were also positive for EBV. These results confirm a recent report that this novel herpesvirus may play a role in AIDS-associated lymphomas especially in those with body cavity presentation.
The aim of the present study was to determine whether hyaluronan (HA) degradation products, which have been shown to be angiogenic in vivo, influence endothelial cell invasion of a 3-dimensional matrix, an essential component of the neovascularization process. Using a previously described in vitro assay, we demonstrate that like the angiogenic cytokines basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), HA oligosaccharides (OHA) induce bovine microvascular endothelial cells to invade a 3-dimensional collagen gel within which they form capillary-like tubes, with an optimal effect at approximately 0.5 to 2 micrograms/ml. Strikingly, co-addition of OHA (0.5 - 2 micrograms/ml) and VEGF (30 ng/ml), but not co-addition of OHA and bFGF (10 ng/ml), induced an in vitro angiogenic response that was greater than the sum of the effects elicited by either agent separately. In contrast to OHA, native high molecular weight HA was consistently inactive, whether added alone or in combination with VEGF or bFGF. Because endothelial cell invasion is believed to require extracellular proteolytic activity, we also investigated the effect of OHA on the plasminogen activator (PA)-plasmin system. OHA (0.01 to 1 microgram/ml) but not native high molecular weight HA induced a dose-dependent increase in mRNA levels of urokinase type PA (uPA), urokinase type PA receptor and PA inhibitor type 1, and a parallel increase in the functional activity of urokinase type PA and PA inhibitor type 1, as determined by zymography and reverse zymography, respectively. The effects of OHA on proteolytic activity were additive with those of VEGF, but not with those of bFGF. Taken together, these results demonstrate that OHA modulate the invasive and proteolytic properties of bovine microvascular endothelial cells and synergize specifically with VEGF in the induction of angiogenesis in vitro. We suggest that the synergism between OHA and VEGF plays a role in the regulation of angiogenesis and that it may be exploited therapeutically in situations that would benefit from stimulation of new blood vessel growth.
A retrospective Medicaid claims data analysis for physician-submitted mammography procedure codes was performed for all continuously eligible female Louisiana Medicaid recipients in 1994. The study measured mammography screening and diagnostic radiology procedures, using CPT coding logic. The study population consisted of 19,688 female Medicaid recipients, age 50 to 65, comprising 55% of the total female Medicaid recipients within Louisiana. In this cohort, 18.3% received a mammogram, with approximately 50% being diagnostic mammography procedures. No significant racial difference in utilization of mammography was found for this population. This claims data analysis suggests that Louisiana's Medicaid population appears to be underserved with respect to mammography screening. The authors conclude that community, physician, and public health resources would be well served to place more emphasis on educational and other outreach programs. Louisiana has to increase its rates for Medicaid recipients by 50% to meet the goal of screening 60% of eligible women every 2 years as set forth in Healthy people 2000, by the United States Public Health Service.
We report the case of a 49-year-old female with severe Goodpasture's syndrome, staghorn calculus, and subacute thyroiditis. Despite the use of a combined therapy with corticosteroid, cyclophosphamide, azathioprine and plasma exchange, we were unable to suppress the disease activity or normalize the anti-glomerular basement membrane (GBM) antibody levels. Disease remission with a parallel reduction in anti-GBM antibody titer was only achieved after sequential bilateral nephrectomy.
We have found a sequence-specific mitochondrial (mt) DNA-binding protein in bovine mitochondria. The binding site designated Mt5 is adjacent to the termination associated sequence in the vertebrate mt displacement loop region and is interspecifically conserved. An UV-crosslinking and gel filtration demonstrated that a Mt5-binding protein (designated Mt5BP) exists in the mitochondria as a homodimer of an approximately 97-kDa polypeptide. The nucleotide sequence of Mt5 is homologous to that of the binding site for the recently reported mt pause-region binding protein (mtPBP) 1 from sea urchin embryo mitochondria. Gel mobility shift competition experiments indicated that Mt5BP can recognize human sequence couterparts for the mtPBP1-binding site. These results suggest that Mt5BP is related to mtPBP1 with respect to discontinuance of heavy-strand synthesis.
Studies on human brains with ischemic insult were performed with immunohistochemical methods to identify antigenic properties of cells participating in that pathology. The 10 patients of whom the brains were obtained at autopsy aged from 51 to 81 years had survived from 3 to 17 days from the onset of stroke to death. Cells involved in the process of decomposition of infarcted tissue were analysed with immunocytochemical methods and CD68, EMB11 (Dako) monoclonal antibody (MAB) was used. Three cell types were visualized e.g. macrophages, astrocytes and microglial cells. Cells identified were numerous in the boundary zone of infarcts and only rarely distributed in the surrounding tissue at a distance from the necrotic tissue. A few cells only were stained in the contralateral hemisphere and none were astrocytes. Our results provide evidence that morphologically different cell types can be marked with the same antibody, which may be in agreement with their similar function in the pathogenesis of ischemic brain stroke.
The CD23 antigen is a low-affinity immunoglubulin E receptor that is expressed during B-cell activation. Recently, it has been shown to be of diagnostic utility in distinguishing between small lymphocytic lymphoma (SLL) and mantle cell lymphoma (MCL), two entities that can have similar morphologic and immunophenotypic features. Such studies, however, generally required viable cells in cell suspension or cryostat sections for detection of CD23. We evaluated staining for the CD23 antigen in paraffin sections, using BU38, an antibody that detects a fixation-resistant epitope of the antigen. We analyzed 44 SLLs, 3 lymphoplasmacytoid lymphomas, and 39 MCLs. Staining was performed on formalin- or B5-fixed paraffin-embedded tissue sections using L26 (CD20), CD3, Leu22 (CD43), and BU38 (CD23) antibodies. All of the cases were of B-cell phenotype (CD20+), and 42/44 SLLs, 3/3 lymphoplasmacytoid lymphomas, and 33/39 MCLs coexpressed the CD43 antigen. CD23 was positive in 41 (93%) of 44 SLLs. The majority of neoplastic cells (75% or more) stained positively, with a membranous pattern of staining. The staining was moderate in intensity and easily interpreted. Only 1/39 MCLs and 1/3 lymphoplasmacytoid lymphomas were CD23 positive. CD23-positive follicular dendritic cells were, however, present in all of the MCLs, either in residual follicles or in large, disordered meshworks. These results demonstrate that the BU38 antibody can detect CD23 on the cells of SLLs in paraffin sections and that this antibody can have diagnostic utility in routine diagnosis.
During two cross sectional surveys in 1988 and 1994 the body mass index among tannery workers in Kanpur, India and its association with exposure to chemicals, dust and awkward ergonomic conditions, socio-economic and health status were studied. Fifty six per cent of the workers had in 1988 a BMI of less than 18.50, the cut-off value for malnutrition. In 1994 the proportion of malnourished workers had decreased to 41 per cent, being statistically significant lower than in 1988. Workers with a high exposure to lifting weights of more than 20 kg had significantly lower BMI than workers without this exposure. No other differences in mean BMI were found between workers without exposure to chemicals, dust and other awkward ergonomic conditions and workers with high or very high exposures, nor did the mean BMI of workers with occupational related conditions such as dermatitis, work related respiratory symptoms and low back pain differ from those without these conditions. There was no association between mean BMI and industrial modifications. In the 1994 survey workers who took sick leave in the year prior to the survey, workers of small/medium sized tanneries and workers without an ESI card had significantly lower BMI than workers without sick leave, workers of large tanneries and workers with an ESI card. Mean BMI of labourers with a monthly income of less than Rs 550 was significantly lower than that of tannery staff not engaged in leather work in this income group. No association was found between mean BMI and smoking, use of alcohol, educational level and income. The nutritional status of labourers in developing countries deserves more attention within the field of occupational health and safety.
Indole alkaloids in Catharanthus roseus have been in focus because of their medicinal value. These alkaloids consist of an indole moiety provided by tryptamine and a terpenoid portion provided by the secologanin. The most important catharanthus alkaloids are vinblastine (VLB), vincristine (VCR) and ajmalicine. VLB and VCR are clinically useful anticancer agents whereas ajmalicine is used for the treatment of circulatory diseases. VCR and VLB are the most expensive because of their low abundance in the plant, and are formed by the coupling of monomeric indole alkaloids vindoline and catharanthine, catalysed by peroxidases. The pathway that lead to monomeric indole alkaloids involves more than 20 enzymes of which 16 enzymes have been isolated and characterized biochemically, and only three at the molecular level. The present state of knowledge on enzymes and genes involved in indole alkaloid biosynthesis and various aspects of their regulation has been discussed.
Influenza is a disease, especially in the elderly, with potentially serious health and fiscal consequences. Vaccines, even though available and proven to be efficacious for prevention, appear to be underutilized in the Medicare population. This paper highlights influenza immunization rates from 1993-1995 for Louisiana Medicare eligible beneficiaries served by Louisiana providers. The authors discuss some of the current efforts underway to increase the number of influenza vaccinations. This was a retrospective study of claims based data on Medicare beneficiaries in Louisiana. Rates were also compared to other states from published Health Care Financing Administration data over the study period. In Louisiana, from 1993-1995, approximately 31% of Medicare beneficiaries age 65 years or older received an influenza vaccination that was paid for by Health Care Financing Administration. This finding indicates an attainment of half of the Department of Health and Human Services Year 2000 goal of 60% influenza immunization rate. The rate for Medicare African-American beneficiaries was approximately one half that of Caucasian beneficiaries. Overall, the billing data indicated that female beneficiaries received influenza immunization slightly more often than male. Medicare beneficiaries aged 75 to 84 years were immunized proportionally more than other age groups. The age group with the smallest percentage of immunized beneficiaries was 85 years or older. These results and rates obtained from the National Health Information Survey and Behavioral Risk Factor Surveillance System for the state collectively indicate marked opportunity for improvement in immunization rates for the State of Louisiana. Health care providers can assist and play an integral role in interventions designed to impact on this vulnerable population in order to meet the Department of Health and Human Services Year 1996 overall goal of 56% influenza immunization rate for all persons age 65 years or older.
The present study assesses central processing of subjective appraisal, expectancy, orientation and reaction time as indexed by Contingent Negative variation (CNV) response in chronic pain patients. Waves N1, P3 and CNV were recorded during a CNV paradigm in a simple reaction time task with a constant interstimulus interval (ISI) of 1 sec. CNV was measured from CZ x FZ in controls and chronic pain patients suffering from cervical spondylosis and low backache due to sciatica. Duration of pain was 5 to 10 years and intensity varied from moderate to severe as adjudged by Visual Analogue Scale. CNV experiment consisted of 32 trials of S1 and S2 motor response sequence. Each trial consisted of warning sound click stimulus (S1) followed by the imperative stimulus in the form of flashes (S2). S2 could be terminated by the subject quickly by pressing a response button with the dominant hand. Cursors were hand set to score the latencies for N1 and P3 potentials to S1, maximal CNV amplitude was scored as the largest negative ongoing potential immediately prior to S2 onset. Similarly Reaction Time (RT), Orientation (O) and Expectancy (E) wave amplitudes and latencies were recorded. There was a significant increase in P3 latency, RT in chronic pain patients, indicating that there is a blunting of cognitive functions and increase in reaction time in patients suffering from chronic pain. These patients also take more time to orient to CNV paradigm.
Although heart attack is caused by occlusion of a major coronary artery, some patients have occlusion without heart attack because these patients have sufficient collateral circulation to provide an alternate pathway for blood supply to the myocardium at ischemic risk. The growth of new capillary vessels (angiogenesis) and enlargement of preexisting vessels play an important role in the collateral development. We evaluated the hypothesis that extracellular matrix metalloproteinase (MMP) expression is altered in coronary collateral arteries (0.5-1 mm o.d.) isolated from canine hearts 2-4 months after surgical placement of an ameroid occluder around the proximal left circumflex artery (n = 4), during the development of collateral vessels and restructuring new vessels. Histologic studies (hematoxylin and eosin, trichrome, and van Gieson stains) indicated cellular proliferation and increased collagen and elastin content in collateral vessels compared with comparable-sized unoccluded arterial segments of the left anterior descending (LAD) artery. In situ MMP activity of collateral vessels, measured using denatured collagen in the gel matrix, indicated an increase in total MMP activity in the intima of collateral vessels compared with normal LAD vessels. To further identify the type of MMP, tissue homogenates were prepared from collateral and LAD vessels and analyzed by SDS-PAGE zymography. The results suggest induction of gelatinase A and gelatinase B expression in collateral vessels compared with normal LAD tissue, when identical amounts of total protein were loaded onto each lane in the gel. Based on plasminogen-casein zymography, we observed the tissue plasminogen activator level to be increased in collateral vessels. On the basis of immunoblot and mRNA (Northern blot) analyses, we determined that the MMP-1 level was induced in collateral vessels 2 and 4 months after ameroid occlusion. In contrast with MMP-1, the level of TIMP-1 (tissue inhibitor of metelloproteinases) was decreased significantly (p < 0.001) in collateral compared with LAD vessels, suggesting a role for arterial TIMP in anti-angiogenic activity. Collectively, these results suggest that chronic occlusion of a major coronary artery induces upregulation of vascular remodeling mechanisms subserving collateral development. Increased MMP-2 activity in collaterals may be associated with decreased levels of tissue inhibitor of metalloproteinases and fibrous tissue remodeling following angiogenic and (or) adaptive responses of the myocardium to chronic ischemia.
Active mouse protection test (AMPT) and enzyme linked immunosorbent assay (ELISA) were used to determine the immunogenicity of whole cell typhoid vaccine when administered in conjunction with either tetanus toxoid (TT) or DEAE-Dextran (DD). Immunization of mice with whole cell typhoid vaccine showed enhanced potency either when administered in conjunction with TT or DD and values were statistically significant (p < 0.05) in comparison to conventional or standard typhoid vaccines. For ELISA, the mice were immunized with 2 different schedules, one in which a single dose of 0.25 ml subcutaneously (s/c) was administered and in another two doses of 0.25 ml each s/c, 14 days apart. In case of single dose schedule of immunization D vaccine (Whole cell typhoid + 5 mg/ml DD) showed significant increase of immune response (3.201 log10) as compared to plain vaccine (2.550 log10). Two dose schedule further increased the titres to 3.856 log10. DD adjuvanted vaccine showed higher potency by AMPT as compared to the TT adjuvanted vaccine or plain vaccine. The present study clearly demonstrates that a single dose of 0.25 ml which is equivalent to half of the conventionally used single human dose of typhoid vaccine adjuvanted with DD can significantly improve the immunogenicity of the vaccine.
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Effect of antidepressant drugs (amitriptyline, imipramine and fluoxetine) on cognitive functions, impaired by the muscarinic antagonist scopolamine were investigated in mice. The changes in learning and memory tasks were studied using transfer latency on elevated plus maze and employing number of descents in passive avoidance paradigms. Amitriptyline and imipramine showed significant memory impairment. They also potentiated scopolamine-induced memory deficit in a significant way. Amitriptyline and imipramine impair cognitive function possibly due to their anticholinergic properties. Fluoxetine, a newer antidepressant, however showed no effect on learning and memory. It significantly reversed the scopolamine-induced memory impairment in both the tests. Fluoxetine with no anticholinergic property may prove to be a better drug in endogenous depression in elderly patients.
We evaluated the effects of nebulized beta 2-adrenergic agonists on pulmonary mechanics in patients with COPD undergoing peripheral surgery with a standardized general anesthetic technique. Thirty males with COPD were randomized into one of three groups. Group I (control group; n = 10) received nebulized saline 3 ml, Group II (n = 10) received nebulized albuterol (2.5 mg in 3 ml), and Group III (n = 10) received nebulized metaproterenol (15 mg in 3 ml). At 20 min after tracheal intubation, the study drugs were nebulized over 20 min. Datex Capnomac Ultima monitor was used to measure pulmonary mechanics on a breath-by-breath basis. There was no difference between the three groups with respect to demographic data and preoperative respiratory parameters. A similar degree of DPH occurred with the initiation of mechanical ventilation in all three groups. Patients receiving nebulized bronchodilators (Groups II and III) displayed a significant decrease in DPH and an increase in total dynamic compliance. However, there were no differences in DPH and total dynamic compliance between Groups II and III. We conclude that nebulization of either albuterol or metaproterenol can alleviate DPH resulting from mechanical ventilation in anesthetized patients with COPD.