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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 1,423 records · Page 79Linked to original sources

Focal mesangiolysis and the pathogenesis of the Kimmelstiel-Wilson nodule.

Kidneys from 74 consecutively autopsied primarily non-insulin-dependent diabetes cases and 59 age-, sex-, and ethnic group-matched controls were examined qualitatively and semiquantitatively to determine whether focal mesangiolyses (FMs), Kimmelstiel-Wilson (KW) nodules, and glomerular capillary microaneurysms (GCMs) were related lesions, to determine their extent and pathogenic sequence, and to look for associations with structural and functional factors. Light microscopic examination of serial sections, immunohistochemical stains, image analysis, and electron microscopy were used. Focal mesangiolyses, KW nodules, and GCMs occurred in 31 of the 74 diabetes cases (27 had FMs, 29 had KW nodules, and nine had GCMs) and were positively correlated with each other semiquantitatively (r = .71, .70, and .68, respectively). Numerous FMs were found, involving 62% and 78% of the glomeruli in the two most severely affected cases. Most FMs were located at the periphery of KW nodules, but de novo FMs were documented in six cases. Glomerular capillary microaneurysms were deemed occasional complications of FMs because they were much less common, and 25 of the 27 GCMs identified were contiguous with FMs. Focal mesangiolyses and GCMs were deemed transient lesions, being absent in end-stage kidneys. Both FMs and KW nodules consisted of a spectrum of lesions. For the sake of clarity they were arbitrarily divided into two types: edematous and proliferative FMs and simple and complicated KW nodules. Their characteristics suggested the following pathogenic sequence: edematous FM-->proliferative FM-->focal nodular mesangial expansion-->simple KW nodule-->recurrent FM-->complicated KW nodule. Complicated nodules were associated with marked alterations in the lobular capillary. The number of mesangial cells was increased in FMs and they were thought to be responsible for increased matrix production. Focal mesangiolyses and KW nodules were positively associated with diabetes, proteinuria, and hyalinization of afferent and efferent arterioles, but were weakly or not associated with hypertension, arcuate and interlobular artery stenosis, hydroenphrosis, acute pyelonephritis, renal arterial atheromatous emboli, glomerular platelet-fibrin thromboemboli, and congestive heart failure.

Autopsy↗

CNS glial cells express neurotrophin receptors whose levels are regulated by NGF.

Normal CNS glial cells manufacture neurotrophin receptors and are competent to respond to NGF. Neurotrophins bind a common receptor (LNGFR) and ligand-specific, tyrosine kinase-containing subunits (TrkA, TrkB, or TrkC). Northern blots and transcription assays reveal complex transcriptional regulation of LNGFR in astrocytes; from undetectable basal levels, NGF dramatically induces LNGFR within 4-6 h. Oligodendrocytes' relatively high basal levels are unaffected by NGF. TrkA mRNA was undetectable, however, TrkB was present and upregulated by NGF in astrocytes but not oligodendrocytes. The results are consistent with receptor autoregulation by its ligand and suggest that NGF plays a role in normal glial functions.

Animals↗

Blood lead levels among populations differentially exposed to vehicular exhaust in Rohtak, India.

In the absence of local industrial sources of lead, leaded gasoline has been suggested as the major source of lead in the urban atmosphere of Rohtak town, situated near Delhi metropolitan city and with a high vehicular density. Blood lead levels were measured in 42 male volunteers from within the Rohtak area with varying degrees of exposure to vehicular exhaust. The occupationally exposed group with a daily exposure of 10-12 h in automobile workshops was found to have the highest levels of blood lead (mean value 21.26 microg dl(-1)) followed by roadside population (mean value 14.91 microg/dl(-1)). This group of people had a daily exposure of 8-10 h in their business establishments, situated at a distance of less than 5 to about 10 ft (< 1.5-c. 3.0 m) from the road with an average traffic density of 8000 vehicles day(-1). Urban residents were found to have higher blood lead levels (mean value 9.85 microg/dl(-1)) than the rural ones (mean value 3.34 microg/dl(-1)). The values were found to increase correspondingly with the increase in age and smoking habits within the particular categories of volunteers. The levels found in the present study are comparable to those reported from other major cities of India, but well within the tolerable limits as recommended by the European Economic Community.

Journal Article↗

Establishment of camel isolates of Haemonchus longistipes and Trichostrongylus colubriformis in goats.

Two main nematode parasites, Haemonchus longistipes and Trichostrongylus colubriformis, have been reported to cause morbidity and mortality in camels. Although goats are usually reared with camels in the combined animal husbandry system prevailing in Northern India, these parasites have not been reported in goats. Therefore, it was planned to conduct an experimental cross-transmission study of H. longistipes and T. colubriformis isolated from camels and transferred to young goats. Twelve healthy kids (5-6 months) were divided into three groups of four each. Groups I and II were infected orally with third stage infective larvae of H. longistipes and T. colubriformis cultured in the laboratory from faecal isolates from camels, at the rate of 50,000 and 100,000 larvae, respectively; group III comprised uninfected healthy controls. Daily clinical and faecal examinations were made. Body weights and blood haematological indices were measured at weekly intervals. The infection became established in both infected groups, and the animals started passing ova 17 days postinfection. Egg counts varied from 275.00 +/- 248.74 to 6150 +/- 2830.63 eggs g-1. Animals were killed 28 days postinfection. On postmortem examination mature as well as immature worms were recovered from the abomasum and intestine with typical postmortem changes seen in both the groups. Clinical manifestations were weakness and loss of body weight but no diarrhoea. There was a marked fall in haemoglobin and packed cell volume, indicating anaemia in both infected groups.

Abomasum↗

Detection of antigens of Mycobacterium tuberculosis in patients of infertility by monoclonal antibody based sandwiched enzyme linked immunosorbent assay (ELISA).

A sandwich ELISA to detect specific protein antigens of Mycobacterium tuberculosis was developed by using polyclonal anti-BCG rabbit antibodies as the primary capture antibodies. The mycobacterial antigens were detected with horseradish peroxidase conjugated monoclonal antibodies (P 6) as secondary antibodies. The enzyme was detected by using 1,2 Phenylenediamine dihydrochloride (OPD) and Hydrogen peroxide as substrate. The antigen could be quantitated through linear regression analysis with lower detection limit of 1.25 micrograms/ml. 50 consecutive cases of infertility were examined by laparoscopy and tested for the presence of the antigen in the serum. Mycobacterial antigen could be detected in 9 of the 12 cases with definitive diagnosis of tuberculosis, 5 of the 23 where the diagnosis of tuberculosis was probable and in only 1 of 15 patients who had no laparoscopic abnormalities indicative of tuberculosis.

Adult↗

Aortoarteritis of abdominal aorta: an angiographic profile in 110 patients.

The angiographic appearances in 110 patients (49 males, 61 females, age range 11-46 years, mean 27.8 years) with aortoarteritis involving the abdominal aorta and/or its branches were analysed. There were 41 aneurysms of the abdominal aorta in 37 patients and eight aneurysms of its branches in as many patients. In 50 patients, 53 obstructive lesions involved the abdominal aorta and were classified as stenoses of focal, segmental and diffuse types and total occlusions. Branch obstructions (182 lesions in 85 patients) affected in order of frequency, the renal, superior mesenteric, coeliac, iliac and the inferior mesenteric arteries. Mesenteric arterial lesions were significantly more common in males (P = 0.01). Collateral circulation through a prominent mesenteric arcade was a distinctive angiographic feature in 28 patients. Computed tomography done in four patients showed peri-adventitial thickening and layered thrombus within aneurysms in three patients, and luminal occlusion of the upper abdominal aorta in one patient. Angiographic appearances in aortoarteritis of the abdominal aorta are characteristic and sufficiently distinctive for definitive diagnosis and appropriate management.

Adolescent↗

Autosomal dominant polycystic kidney disease: localization of the second gene to chromosome 4q13-q23.

At least two loci are known to exist for autosomal dominant polycystic kidney disease (ADPKD). One was localized to 16p, but the second less common locus has remained unlinked. Over 100 microsatellite markers, distributed across all chromosomes, have been typed on informative family members from the large Sicilian kindred in which the genetic heterogeneity was first discovered. Both the affected and the unaffected status of every family member used in the study were confirmed by renal ultrasonography. This search has resulted in the successful localization of a second ADPKD gene to chromosome 4q. It was found to be flanked by the markers D4S231 and D4S414, defining a segment that spans about 9 cM. The new locus has been designated PKD4. This second localization will allow researchers to target another ADPKD gene for isolation in an effort to understand the pathogenesis of this common disorder. Furthermore, when flanking markers for the second ADPKD gene are used in conjunction with flanking markers for PKD1, the accuracy of the diagnosis of the subtype of ADPKD present in any particular family will be enhanced. This will improve the accuracy of linkage-based presymptomatic diagnoses by reducing the error due to genetic heterogeneity.

Chromosome Mapping↗

Selective modification and immune evasion: a hypothesis.

A hypothesis is proposed asking why enzyme neutralization is not an effective host-response to a parasite despite the fact that some parasite housekeeping enzymes are highly immunogenic. It is hypothesized that although the structural domain can be immunogenic, the active sites of the parasite enzyme molecules have converged evolutionarily to resemble the functional part (active sites) of host's enzyme molecules, by structural modification/rearrangement (amino acid substitution/polypeptide chain folding) with the effect: (i) of functional adaptation to the host environment; and (ii) to escape detection of active sites by the host as non-self, allowing the parasite to be exposed to antiparasite enzyme antibodies, without deleterious effects on the parasite.

Animals↗

Relationship between serum butyrylcholinesterase activity, hypertriglyceridaemia and insulin sensitivity in diabetes mellitus.

1. The activity of serum butyrylcholinesterase ('pseudocholinesterase', EC3.1.1.8) was investigated in 56 patients with type 1 diabetes mellitus, 51 patients with type 2 diabetes mellitus and 101 healthy control subjects. 2. Butyrylcholinesterase activity was significantly elevated in both type 1 (8.10 +/- 3.35 units/ml) and type 2 (7.22 +/- 1.95 units/ml) diabetes compared with the control subjects (4.23 +/- 1.89 units/ml) (P < 0.001). 3. In the patients with type 1 and type 2 diabetes, serum butyrylcholinesterase activity was correlated with log serum fasting triacylglycerol concentration (r = 0.41 and r = 0.43, respectively, P < 0.001). In the type 2 population serum butyrylcholinesterase activity was also correlated with insulin sensitivity (r = -0.51, P < 0.001). 4. Serum butyrylcholinesterase activity was unrelated to age, gender, serum gamma-glutamyltranspeptidase activity, body mass index, or treatment for diabetes in both the diabetic populations. 5. In 37 non-diabetic patients with butyrylcholinesterase deficiency serum triacylglycerol levels were in the normal range. 6. These results are consistent with the view that butyrylcholinesterase may have a role in the altered lipoprotein metabolism in hypertriglyceridaemia associated with insulin insensitivity or insulin deficiency in diabetes mellitus.

Butyrylcholinesterase↗

Effect of diabetes mellitus on the cardiovascular responses to induction of anaesthesia and tracheal intubation.

We have compared cardiovascular responses to induction of anaesthesia and to tracheal intubation after propofol 2.5 mg kg-1 and pancuronium 0.1 mg kg-1 in 10 diabetic and 10 matched, non-diabetic (control) ASA I patients. Anaesthesia was maintained with 0.8% enflurane and 50% nitrous oxide in oxygen, with assisted ventilation. The trachea was intubated 3 min after induction of anaesthesia. All 10 diabetic patients (but no controls) had abnormal autonomic function when tested on the day before surgery. There was no difference between the two groups in the pre-induction cardiovascular state. Mean arterial pressure and vascular resistance decreased after induction in each group (P < 0.05). Heart rate increased (P < 0.01) and cardiac index was sustained in the control group, but in the diabetic group heart rate did not change and cardiac index decreased (P < 0.01). There was an earlier decrease in stroke index in the diabetic group (2 min) compared with the controls (5 min). After tracheal intubation, heart rate and cardiac index in the control group and cardiac index in the diabetic group remained unchanged. However, there was a greater increase in heart rate, mean arterial pressure and vascular resistance in the diabetic group compared with the controls after tracheal intubation (P < 0.05). The exaggerated pressor response to tracheal intubation, in the diabetic patients, may reflect autonomic dysfunction.

Adult↗

Bacterial and mammalian cell mutagenicity of four optically active bay-region 10,11-diol-8,9-epoxides of the nitrogen heterocycle dibenz[a,h]acridine.

The mutagenic activities of the enantiomers of the diastereomeric pair of bay-region 10,11-diol-8,9-epoxides of dibenz[a,h]acridine (DB[a,h]ACR) were evaluated in histidine-dependent strains of Salmonella typhimurium and in cultured Chinese hamster V79 cells. In strains TA98 and TA100 of S.typhimurium, the (-)-[8S,9R,10R,11S] diol-epoxide was the most mutagenic compound, inducing 1200 and 6900 His+ revertants/nmol respectively. The mutagenic activity of each of the remaining three isomers was essentially independent of the bacterial strain used and had 14-72% of the activity of the [S,R,R,S] isomer. However, in Chinese hamster V79 cells, the (+)-[8R,9S,10S,11R] diol-epoxide was the most mutagenic compound (68 8-azaguanine resistant variants/nmol/10(5) cells), inducing from 2 to 11 times as many mutations as the other three isomers. These results are analogous to previous studies with the bay-region diol-epoxides of other polycyclic hydrocarbons in that the isomer with [R,S,S,R] absolute configuration has had variable activity in the bacterial assays, but has generally been the most active in the mammalian cells. Furthermore, this isomer has almost always been highly tumorigenic in the mouse.

Acridines↗

Transformation of immortal, non-tumorigenic osteoblast-like human osteosarcoma cells to the tumorigenic phenotype by nickel sulfate.

Epidemiological studies have indirectly linked compounds of chromium, nickel and arsenic to human carcinogenesis. However, there is no evidence that metal compounds can transform human cells to the tumorigenic phenotype in culture. We show here that exposure to 36 microM NiSO4 for 48-96 h results in transformation of an immortal, nontumorigenic, osteoblast-like cell line, HOS TE85, to the tumorigenic phenotype. Continuous passaging following treatment leads to the formation of a few dense foci. The cells isolated and expanded from the foci are morphologically transformed, and form anchorage-independent colonies of the size and abundance comparable to that formed by Kirsten murine sarcoma virus transformed HOS TE85 cells. The transformed cells from tumors in nude mice, have enhanced levels of plasminogen activators and have lost the ability to form model bone matrix on extended culture in the presence of ascorbic acid and beta-glycerophosphate. A number of cell lines have been established from nude mouse tumors. Cytogenetic analysis reveals 16 marker chromosomes and an aberrant chromosome 16. This is the first report of the transformation of a human cell line to tumorigenic phenotype by a metal carcinogen.

Animals↗

Epstein-Barr virus-associated T-cell lymphoma in a renal transplant patient.

Posttransplant lymphoproliferative disorders in organ allograft recipients are most commonly of B cell origin, whereas T cell lymphomas are rarely described. We report a case of T cell immunoblastic large cell lymphoma associated with Epstein-Barr virus (EBV) that occurred in a recipient of a cadaveric renal transplant 7 years posttransplantation. On paraffin immunophenotyping, none of the neoplastic cells stained with the T cell-associated markers used, but did show strong CD30 expression. Flow cytometric studies revealed a predominance of T cells without definite evidence of T cell neoplasia. Frozen section immunophenotyping studies revealed a T cell phenotype with aberrant expression, and genotypic studies demonstrated T cell receptor beta gene rearrangement with germline configuration of immunoglobulin heavy chain and kappa light chain genes, confirming a T lineage. EBV-encoded RNA transcripts were demonstrated within the neoplastic cells by in situ hybridization. Southern blot analysis using probes derived from the terminal repeat region of the virus detected a single restriction band indicating a clonal population. We believe this is the first case of a posttransplant T cell lymphoma in which the EBV genome has been demonstrated. This case also illustrates the pitfalls of paraffin immunophenotyping in the diagnosis of T cell lymphoma.

Adult↗