Extensive S aureus spinal epidural empyema.
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Cerebrospinal Fluid↗
Biomedical subjects
S Sagar
Publications and source records attributed to S Sagar.
Found: Na(+) and K(+) binding sites of the sodium pump.
Homology modeling and valence mapping have been used to predict the location and structure of Na(+) and K(+) binding sites in the Na(+)-K(+)-ATPase on the basis of the known atomic resolution structure of SERCA. Additional sites are predicted that may be associated with intracellular access and extracellular egress pathways for Na(+). The model predictions are in excellent agreement with previous structure-function and electrical studies.
Amino Acid Sequence↗
The effects of stress on oncology staff.
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Burnout, Professional↗
Quantitation of nucleolar organizer regions by image analysis in glottic squamous cell carcinoma.
OBJECTIVE: To apply computer image analysis as a quantitative method for analyzing interphase nucleolar organizer regions (NORs) to determine whether this proliferative marker provides useful prognostic information in glottic squamous cell carcinoma. DESIGN: Retrospective testing of biopsy samples and resected tissue. SETTING: Nova Scotia Regional Cancer Centre and regional hospitals in Nova Scotia and Prince Edward Island, Canada. PATIENTS: Patients with primary glottic cancer presenting to the cancer centre between 1984 and 1991. INTERVENTIONS: Semiautomated image analysis was used to measure the nuclear area and the NOR area in formalin-fixed paraffin-embedded tumour samples. OUTCOME MEASURES: Mean nuclear area, mean NOR area and NOR percentage of nuclear area, calculated as the mean NOR area divided by the mean nuclear area, expressed as a percentage. RESULTS: Of 154 cases, 90 samples were received; however, 8 paraffin blocks were exhausted and 29 samples stained poorly due to extent of fixation. Analysis of the remaining 53 cases, all primary squamous cell carcinomas, showed no statistically significant association between, on one hand, mean NOR area or NOR percentage of nuclear area and, on the other hand, tumour grade, tumour stage, tumour recurrence or disease-related death. CONCLUSIONS: This study does not demonstrate a prognostic value of NOR measurement as a proliferative marker in primary glottic squamous carcinoma. However, given the small number of cases in this study, further research should be conducted using a larger number of cases from one centre and comparing NOR measures with other markers of cell proliferation.
Biomarkers, Tumor↗
HIV-1 gp120 envelope protein and morphine-tubular cell interaction products modulate kidney fibroblast proliferation.
BACKGROUND: Renal interstitial scarring is an important feature of HIV-associated nephropathy. Intravenous drug abuse has been demonstrated to be a risk factor for the development of HIV-associated nephropathy in patients with HIV infection. We studied the effect of tubular cell-morphine and/or HIV-1 gp120 envelope protein interaction products on kidney fibroblast (KF) proliferation and apoptosis. METHODS: Tubular cell-morphine and/or gp120 interaction products were prepared by incubating confluent human proximal tubular cells with buffer (TCP), morphine (10(-3) mol/L) (TCM-IP), gp120 (0.01 microgram/mL)(TC-120IP), or morphine (10(-3) mol/L) + gpl20 (0.01 microgram/mL) (TCM-120IP). To evaluate the effect of tubular cell interaction products (TCIP) on KF proliferation, growth arrested kidney fibroblasts were treated with variable concentrations (5%, 10%, 20%, 30%, and 50%) of TCP, TCM-IP, TC-120IP, or TCM-120IP for 48 hours. To evaluate the role of cytokines in TCIP-induced KF proliferation, cells were incubated with TCIP with or without cytokine neutralizing antibodies to TGF-beta, TNF-alpha, FGF, or IL-6 for 48 hours. Subsequently, cells were counted in a hemocytometer (n = 3). To evaluate the effect of TCIP on KF apoptosis, cells were treated with 50% TCP, 50% TCM-IP, 50% TC-120IP, or 50% TCM-120IP for 24 hours and stained with H-33342 and propidium iodide. In parallel experiments KFs were harvested under identical conditions, DNA was isolated and run on gel electrophoresis. To evaluate the role of early growth genes in TCM-120-induced KF proliferation, TCM-120IP-treated cells were probed with cDNA for c-fos and c-jun. RESULTS: TC-120IP at a lower concentration (20%) enhanced (P < 0.001) proliferation of KF when compared with TCP. TCM-IP did not stimulate KF proliferation. On the contrary, TCM-120IP at a lower concentration (20%) promoted (P < 0.001) KF proliferation when compared with TCP, TCM-IP and TC-120IP. TCM-120IP at a lower concentration (20%) also enhanced KF mRNA expression of c-fos and c-jun. TCM-120IP enhanced KF proliferation in a dose-dependent manner. All tubular cell interaction products at a higher concentration (50%) promoted apoptosis of KF. CONCLUSIONS: Tubular cell-gp120 interaction products stimulated KF proliferation. Morphine amplified the effect of tubular cell-gp120 interaction on the proliferation of KF. TCM-120IP-induced KF proliferation may be mediated through the expression of early growth genes; whereas TCM-120IP-induced KF growth suppression may be mediated through the induction of apoptosis.
Acquired Immunodeficiency Syndrome↗
Direct role of HLA-B5 in influencing susceptibility to Takayasu aortoarteritis.
To investigate genetic factors involved in the pathogenesis of Takayasu arteritis (TA), North Indian patients belonging to the states of Punjab, Haryana, Uttar Pradesh and Delhi were examined for HLA-class I and class II antigens and the data compared with healthy controls from the same ethnic group. Additionally, DNA typing was performed using polymerase chain reaction/sequence specific oligonucleotide probe (PCR-SSOP) technique to evaluate the distribution of molecular alleles in the healthy Indian population as compared to orientals and Western caucasoids. The frequency of HLA-B5 was significantly increased in patients as compared to controls (chi 2 = 32.5, corrected P value, Pc = 3 x 10(-6), relative risk = 4.3). Serological splitting of B5 into B51 and B52 did not reveal an association with any of the two subtypes. Weak association was also noticed with DR8 in the patient group (chi 2 = 8.2, Pc = 0.05). Distribution of the molecular subtypes of various HLA-B and DR alleles indicated that although the Indian population is essentially caucasoid, it comprises of an admixture of both caucasoid as well as oriental alleles/haplotypes. The observations clearly suggest that (a) HLA-linked genes are involved in the development of Takayasu arteritis, and (b) rather than a subtype of B5, the whole molecule or its closely linked gene(s) influence susceptibility to TA.
Adolescent↗
Systemic manifestations of Takayasu arteritis: the expanding spectrum.
Takayasu arteritis (TA) is a chronic inflammatory and obliterative disease of large vessels particularly the aorta and its major branches. Recently, the disease has been shown to involve the parenchyma of various organs. Specific glomerular lesions reported in patients with TA are mesangial proliferative, membrano-proliferative, crescentic glomerulonephritis and amyloidosis. Dermatological manifestations of this disease are erythema nodosum, facial lupus rash and erythema induratum. Dilated cardiomyopathy, myocarditis and pericarditis have been reported in TA. Rarely, interstitial lung disease, pneumonic consolidation, idiopathic ulcerative colitis, rheumatoid arthritis and polymyositis have been described in association with TA. In this report, five patients of TA with primary parenchymatous involvement of kidneys, skin, heart and gastrointestinal tract have been described. An association of primary parenchymatous organ involvement and TA suggests an autosensitization to an unidentified antigen in the pathogenesis of TA.
Adolescent↗
Morphine modulates mesangial immunoglobulin G uptake in rats with antithymocyte serum-induced mesangial cell injury.
The glomerular mesangium is an important site of activity in patients with heroin addiction. We studied the effect of morphine, a metabolite of heroin, on the mesangial immunoglobulin G aggregate uptake in a model of specific mesangial cell injury. Isolated specific mesangial cell injury was developed in Lewis rats by injecting intravenously antithymocyte serum (ATS). Forty-eight hours later, radioiodinated, heat aggregated immunoglobulin G (AHIgG125I) was administered (20 mg/100 g i.v.) by tail vein. At 4 and 24 h, kidneys, liver, and spleen were removed, glomeruli isolated, and the radioactivity measured. Blood levels of AHIgG125I were measured at 0, 4 and 24 h. For ultrastructural studies, IgG-coated gold particles were injected, and the mesangial circulation was studied. At 4 h, ATS-treated rats showed a lower (p < 0.02) accumulation of AHIgG125I in the mesangium when compared with control rats (controls 511,012 +/- 10,807 vs. ATS 464,614 +/- 7,944 cpm/g glomerular protein). ATS plus morphine treated rats showed a higher (p < 0.01) accumulation of of AHIgG125I when compared with rats treated with AS alone. Even at 24, h morphine-treated ATS rats showed a higher accumulation of AHIgG125I when compared with those treated with ATS alone. Ultrastructural studies showed aggregation of IgG-coated gold particles in the mesangial cell endolysosomes of control rats. Our results suggest that macromolecules may dwell longer in the mesangium of rats with intact mesangial cells. This increase in transit time may be related to the uptake of these macromolecules by mesangial cells. Morphine seems to enhance the accumulation of macromolecules in the mesangium, independent of its action on mesangial cells.
Animals↗
Simulated glomerular pressure modulates mesangial cell 72 kDa metalloproteinase activity.
Glomerular hypertension has been considered to play an important role in the development of glomerulosclerosis. Mesangial expansion, a precursor of glomerulosclerosis, may be dependent not only on synthesis of matrix but also on degradation of the deposited matrix. In the present study we investigated the effect of simulated glomerular pressure on 72 kDa metalloproteinase activity (measured as degradation of gelatin) of mesangial cells. To simulate glomerular pressure conditions we have used an in vitro mechanical stretch/relaxation system as well as an alternative system which allowed direct application of pressure on mesangial cells. Mesangial cells were grown either under control (no added pressure), stretch/relaxation, or direct mean pressure of 45-50 mm Hg (physiologic glomerular pressure) conditions. Mesangial cells grown under stretch/relaxation showed a higher (P < 0.02) level of 72 kDa metalloproteinase activity when compared with control cells (control, 6.9 +/- 0.8 vs. stretch, 9.9 +/- 0.5 ng gelatin degraded/micrograms protein). Similarly, direct stimulated glomerular pressure increased (P < 0.01) mesangial cell 72 kDa metalloproteinase activity when compared with control cells. The effect of mechanical strain on mesangial cell 72 kDa metalloproteinase activity peaked at the end of the third day (control, 4.5 +/- 1.1 vs. stretch 15.3 +/- 1.1 ng gelatin degraded/micrograms protein, P < 0.001). Both mechanical strain and direct pressure to mesangial cells modulated 72 kDa metalloproteinase activity in a dose dependent manner. Mechanical stretch equivalent to normal simulated glomerular pressure increased mesangial 72 kDa metalloproteinase activity by 88%; whereas mesangial cell 72 kDa metalloproteinase activity declined to basal levels at higher simulated glomerular pressure (equivalent to 100 mm Hg). Likewise, direct higher pressure (100 mm Hg) also lowered 72 kDa metalloproteinase activity to basal levels. These results indicate that higher glomerular pressure inhibits degradation of type IV collagen. This may cause an accumulation of extracellular matrix and may thus be contributing to the expansion of the mesangium.
Animals↗
Activation of transfer RNA-guanine ribosyltransferase by protein kinase C.
Transfer RNA-guanine ribosyltransferase (TGRase) irreversibly incorporates queuine into the first position in the anticodon of four tRNA isoacceptors. Rat brain protein kinase C (PKC) was shown to stimulate rat liver TGRase activity. TGRase preparations derived from rat liver have been observed to decrease in activity over time in storage at -20 or -70 degrees C. Contamination of the samples by phosphatases was indicated by a p-nitrophenylphosphate conversion test. The addition of micromolar concentrations of the phosphatase inhibitors sodium pyrophosphate and sodium fluoride into TGRase isolation buffers resulted in a greater return of TGRase activity than without these inhibitors. Inactive TGRase preparations were reactivated to their original activity with the addition of PKC. In assays combining both TGRase and PKC enzymes, inhibitors of protein kinase C (sphingosine, staurosporine, H-7 and calphostin C) all blocked the reactivation of TGRase, whereas activators of protein kinase C (calcium, diacylglycerol and phosphatidyl serine) increased the activity of TGRase. None of the PKC modulators affected TGRase activity directly. Alkaline phosphatase, when added to assays, decreased the activity of TGRase and also blocked the reactivation of TGRase with PKC. Denaturing PAGE and autoradiography was performed on TGRase isolates that had been labelled with 32P by PKC. The resulting strong 60 kDa band (containing the major site for phosphorylation) and weak 34.5 kDa band (containing the TGRase activity) are suggested to associate to make up a 104 kDa heterodimer that comprises the TGRase enzyme. This was corroberated by native and denaturing size-exclusion chromatography. These results suggest that PKC-dependent phosphorylation of TGRase is tied to efficient enzymatic function and therefore control of the queuine modification of tRNA.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Morphine modulates cathepsin B and L activity in isolated glomeruli and mesangial cells.
Altered matrix degradation may be playing a role in the development of initial mesangial expansion and subsequent glomerulosclerosis in persons with heroin abuse. We studied whether morphine, a metabolite of heroin, had any effect on lysosomal content of cathepsin B and L in mesangial cells. Morphine (10(-6) M) increased (P < 0.01) mesangial cathepsin B and L activity (control, 22.1 + 2.2 vs. morphine, 31.4 + 1.4 mol NMec/microgram protein, N = 5). Morphine (10(-6) M) also increased (P < 0.01) glomerular cathepsin B and L activity (control, 0.1 + 0.01 vs. morphine, 2.2 +/- 0.2 pmol NMec/microgram protein, N = 3). This effect of morphine occurred in a dose-dependent manner. These results suggest that morphine enhances cathepsin B and L activity in mesangial cells and isolated glomeruli. This effect of morphine may enhance capacity of mesangial cells to degrade increased amount of mesangial macromolecules.
Animals↗
Morphine enhances deposition of ferritin-antiferritin complexes in the glomerular mesangium.
Since increased mesangial accumulation of matrix has been considered to be an important event in the development of focal glomerulosclerosis, we investigated whether morphine, an active metabolite of heroin, can modulate mesangial accumulation of immune complexes. Control or morphine-dependent rats were administered intraperitoneal ferritin (8 mg/100 g body weight) daily for 6 weeks. Body weight, blood pressure, serum creatinine, 24-hour urinary protein and creatinine excretion rates were measured at 3-week intervals. Rats were sacrificed at the end of 6 weeks and kidney tissue was studied by light, immunofluorescence and electron microscopy. Serum creatinine levels and urinary protein excretion rates were not different between control and morphine-dependent rats. All morphine-dependent rats developed hematuria, whereas only 1 control rat developed hematuria. Light microscopy revealed no proliferation of mesangial cells and only a minimal increase in the mesangial matrix. Electron-microscopic studies showed deposition of immune complexes in the mesangial region. Mesangial cells showed aggregation of ferritin in lysosomes. Immunofluorescence studies revealed the presence of IgG staining predominantly in the mesangial region. The majority (60%) of morphine-dependent rats showed a diffuse mesangial deposition of IgG when compared to control rats (83%) who showed only focal deposition. These results indicate that morphine enhances deposition of immune complexes in the mesangium. Morphine-induced matrix but may also change its quality. This may play a pathogenic role in the development of glomerular lesions in patients who abuse opiates.
Animals↗
Vasoactive agents modulate matrix metalloproteinase-2 activity by mesangial cells.
Vasoactive agents alter proteinuria by modulating glomerular hemodynamics. The authors hypothesized that vasoactive agents may be altering degradation of the collagen component of glomerular basement membrane, which also may be contributing to proteinuria. Mesangial cells treated with 10(-6) M angiotensin II had higher (P < 0.01) metalloproteinase activity (MA) when compared with control cells. This effect of angiotensin II was dose dependent. Amlodipine (10(-6) M), a calcium channel blocker, inhibited MA (control, 5.86 +/- 0.08 microgram versus 4.13 +/- 0.06 microgram gelatin degraded/mg protein, P < 0.001). The decrease in mesangial MA caused by amlodipine also occurred in a dose dependent manner. Amlodipine attenuated (P < 0.05) angiotensin II-stimulated MA (control, 6.69 +/- 0.30 micrograms, angiotensin II, 10.68 +/- 0.49 micrograms, angiotensin II+amlodipine 8.29 +/- 0.30 micrograms gelatin degraded/mg protein). Prostaglandin E2 increased (P < 0.001) MA (control, 10.22 +/- 0.9 micrograms versus prostaglandin E2, 17.9 +/- 0.9 micrograms gelatin degraded/mg protein), whereas indomethacin, a prostaglandin inhibitor, attenuated the metalloproteinase activity (control, 9.67 +/- 0.32 micrograms vs. 10(-6) M indomethacin, 4.22 +/- 0.31 micrograms gelatin degraded/mg protein, P < 0.001). Indomethacin also inhibited angiotensin II-stimulated MA (angiotensin II, 18.66 +/- 0.46 vs. angiotensin II+indomethacin, 11.86 +/- 0.56 micrograms degraded/mg protein, P < 0.001). Similarly, meclofenamate, another prostaglandin inhibitor, attenuated (P < 0.001) angiotensin II-induced MA. Because angiotensin II increases prostaglandin E2 synthesis by mesangial cells, it appears that increased MA, induced by angiotensin II, may be mediated partly through the generation of prostaglandin E2.
Amlodipine↗
Human immunodeficiency virus-1 gp120 and gp160 envelope proteins modulate mesangial cell gelatinolytic activity.
Patients with human immunodeficiency virus (HIV) infection often develop glomerular lesions (mesangial expansion and sclerosis). Modulation of matrix degradation may be important in the expansion of the mesangium. We studied the effect of HIV sera and HIV-1 envelope glycoproteins on gelatinolytic activity of human mesangial cells. HIV serum-treated cells showed lower (P < 0.01) gelatinolytic activity when compared with cells treated with control serum (control serum, 4.3 +/- 0.1 versus HIV serum, 3.3 +/- 0.1 micrograms gelatin degraded/mg protein). Mesangial cells incubated with HIV-1 gp120 protein also showed decreased (P < 0.01) gelatinolytic activity (control, 4.6 +/- 0.2 versus HIV-1 gp120 protein, 1.7 +/- 0.2 micrograms gelatin degraded/mg protein). HIV-1 gp160 protein also inhibited (P < 0.05) mesangial cell gelatinolytic activity as judged by a biotin-avidin assay as well as by a 3H gelatin degradation assay. In contrast, gp alpha-1 acid, a nonviral glycoprotein, did not modulate mesangial cell gelatinolytic activity. These results suggest that the serum contents of HIV patients decrease gelatinolytic activity of mesangial cells. This effect of HIV sera seems to be mediated through HIV-1 gp proteins.
Acquired Immunodeficiency Syndrome↗
Glomerular metalloprotease activity modulates the development of focal segmental glomerulosclerosis.
Focal segmental glomerulosclerosis (FSGS) is a common outcome of a variety of renal diseases. Among laboratory animals both puromycin aminonucleoside (PAN) and hypertension produce a similar histological pattern. Since mesangial expansion is a precursor of FGS and decreased degradation of matrix can cause expansion of mesangium we studied the glomerular matrix metalloprotease activities in the development of FSGS. Dahl salt sensitive (SS) and salt resistant (SR) rats were fed 8% salt diet for six weeks. Kidney biopsy showed features of FSGS in SS rats. Glomeruli were isolated and metalloprotease activity was measured. Sprague-Dawley rats were administered subcutaneously either saline (S) or saline containing PAN (1.67 mg/100 g B. W.) daily for 7 days. Kidney biopsy was done at day 7 and the isolation of glomeruli was performed at day 10 and at 6 weeks. Renal histology showed features of FSGS in PAN rats at 6 weeks. Glomerular metalloprotease activity was decreased in SS (SR, 148 +/- 12 vs. SS, 73 +/- 9 cpm/microgram protein, p < 0.01) as well as in PAN rats (S, 31 +/- 5 vs. PAN, 12 +/- 1 cpm/microgram protein, p < 0.01). These results suggest that decreased glomerular metalloprotease activity may play a role in the development of FSGS in SS and PAN rats.
Animals↗
Morphine modulates 72-kDa matrix metalloproteinase.
Mesangial expansion is considered to be a precursor of glomerulosclerosis, a predominant glomerular lesion in heroin nephropathy. In addition to matrix synthesis, matrix degradation may also contribute to expansion of mesangium. In this study, we evaluated the effect of morphine on metalloproteinases (gelatinases) that degrade type IV collagen and are secreted by mesangial cells (MC). Gelatinolytic activity was significantly decreased in media of MC exposed to morphine for 1 wk compared with control [control, 2,411.6 +/- 198.7; morphine (10(-6) M), 954.4 +/- 112.2 ng.mg protein-1.3 h-1; P < 0.001]. A similar effect was seen at 2 wk [control, 17,010.6 +/- 1,789.5; morphine (10(-6) M), 8,925.2 +/- 1,623.5 ng.mg protein-1.3 h-1; P < 0.02]. Percent change in gelatinolytic activity was 39.58% (1 wk) and 47.53% (2 wk) compared with control. Morphine at concentrations of 10(-10) to 10(-6) M decreased gelatinolytic activity in MC. In in vivo studies, 24-h urines of morphine-treated rats showed a lower (P < 0.01) gelatinolytic activity when compared with controls. Isolated glomeruli from morphine-treated rats also showed decreased (P < 0.05) gelatinolytic activity compared with control. Naloxone, an opioid antagonist, did not inhibit the effect of morphine on gelatinolytic activity of MC. These results suggest that morphine may cause a decrease in degradation of type IV collagen in patients with heroin addiction. Accumulation of collagen because of lack of gelatinolytic activity in the mesangium may contribute to the expansion of mesangium.
Animals↗
Comparative studies of patients with Takayasu arteritis in Japan, Korea and India--comparison of clinical manifestations, angiography and HLA-B antigen.
Comparative study of Takayasu arteritis in 3 Asian countries (India, Korea and Japan) has revealed some significant differences. In angiographic findings, Japanese patients more frequently have lesions at the aortic arch and/or its branches (99% of 96 cases), while most lesions in Korean (76% of 109 cases) and Indian patients (92% of 50 cases) are at the abdominal aorta. The presence of HLA-Bw52 or B5 is closely associated with Takayasu arteritis in all 3 Asian countries. The complications in 108 Japanese, 101 Korean and 50 Indian patients were also compared. The most frequent complications were aortic regurgitation in Japan and hypertension in the other 2 countries. Death occurred most frequently due to congestive heart failure or sudden death resulting from aortic regurgitation in Japan, but resulting from hypertension in Korea and India.
Adolescent↗
Malignant hypertension in north west India. A hospital based study.
One hundred and thirty-five patients with malignant hypertension seen over a period of 11 years (1979 to 1989) at a referral hospital were analyzed to characterize the clinical features and etiology of this disease. Ninety male and 45 female patients with an average age of 38.2 +/- 1.4 years were studied. Malignant hypertension was the presenting feature in 68 patients. The etiology included essential hypertension in 88 patients and a secondary cause in 47 patients. Secondary causes included a renovascular etiology in 20 patients, renal parenchymal disease in 19, pheochromocytoma in 6 and Conn's syndrome and adrenal carcinoma in one patient each. Among the 20 patients with renovascular hypertension, Takayasu's arteritis was seen in 15 (75%). The mean age of patients with essential hypertension was 41.7 + 1.14 years while the mean age in patients with secondary hypertension was 33.2 + 1.96 years. Duration of preexisting hypertension was longer in essential hypertensives (2.42 + 0.45 years) than in patients with secondary hypertension (1.27 + 0.41 years, p < 0.05). Raised serum creatinine was seen in 93 patients. Seventy-seven patients had left ventricular hypertrophy on ECG. Ninety-six patients were followed for a period ranging from 18 months to 10 years (mean 32 months). Sixteen patients died during hospital stay while 6 patients died during the follow-up period. The deaths were related to the effects of uncontrolled hypertension including, renal failure (11), stroke (6), congestive cardiac failure (3) and myocardial infarction (1).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗