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Biomedical subjects

K Sharma

Publications and source records attributed to K Sharma.

At least 127 records · Page 7Linked to original sources

Stimulation of collagen gene expression and protein synthesis in murine mesangial cells by high glucose is mediated by autocrine activation of transforming growth factor-beta.

Previous investigations have demonstrated that growing mesangial cells in high glucose concentration stimulates extracellular matrix synthesis and also increases the expression of TGF-beta. We tested whether the stimulation of extracellular matrix production is mediated by autocrine activation of TGF-beta, a known prosclerotic cytokine. Addition of neutralizing anti-TGF-beta antibody, but not normal rabbit IgG, significantly reduced the high glucose-stimulated incorporation of 3[H]proline. Denaturing SDS-PAGE revealed that mainly collagen types I and IV were stimulated by high (450 mg/dl) D-glucose. This high glucose-mediated increase in collagen synthesis was reduced by the anti-TGF-beta antibody. Treatment of mesangial cells grown in normal (100 mg/dl) D-glucose with 2 ng/ml recombinant TGF-beta 1 mimicked the effects of high glucose. Furthermore, the anti-TGF-beta antibody significantly reduced the increase in mRNA levels encoding alpha 2(I) and alpha 1(IV) collagens induced by high glucose. Thus, the high glucose-stimulated increase of collagen production in mesangial cells is mediated, at least in part, by autocrine TGF-beta activation. We postulate that the interception of the glomerular activity of TGF-beta may be an effective intervention in the management of diabetic nephropathy.

Animals↗

Development of specific muscle and cutaneous sensory projections in cultured segments of spinal cord.

Development of sensory projections was studied in cultured spinal segments with attached dorsal root ganglia. In spinal segments from stage 30 (E6.5) and older chicken embryos, prelabeled muscle and cutaneous afferents established appropriate projections. Cutaneous afferents terminated solely within the dorsolateral laminae, whereas some muscle afferents (presumably Ia afferents) projected ventrally towards motoneurons. Development of appropriate projections suggests that sufficient cues are preserved in spinal segments to support the formation of modality-specific sensory projections. Further, because these projections developed in the absence of muscle or skin, these results show that the continued presence of peripheral targets is not required for the formation of specific central projections after stage 29 (E6.0). Development of the dorsal horn in cultured spinal segments was assessed using the dorsal midline as a marker. In ovo, this midline structure appears at stage 29. Lack of midline formation in stage 28 and 29 cultured spinal segments suggests that the development of the dorsal horn is arrested in this preparation. This is consistent with earlier reports suggesting that dorsal horn development may be dependent on factors outside the spinal cord. Because dorsal horn development is blocked in cultured spinal segments, this preparation makes it possible to study the consequences of premature ingrowth of sensory axons into the spinal cord. In chicken embryos sensory afferents reach the spinal cord at stage 25 (E4.5) but do not arborize within the gray matter until stage 30. During this period dorsal horn cells are still being generated. In spinal segments, only those segments that have developed a midline at the time of culture support the formation of midline at the time of culture support the formation of specific sensory projections.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Serum cytokine levels in patients with neutropenia.

Serum samples from 76 patients with neutropenia and 34 control subjects were analyzed for levels of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin 1 alpha, and tumor necrosis factor beta. Clinical correlates and duration of neutropenia were determined insofar as possible. Systemic acute inflammatory disease was present in only two patients. In most cases, the neutropenia was considered idiopathic or medication related. Significantly elevated serum granulocyte colony-stimulating factor levels were found in the patient group, regardless of the apparent cause of the neutropenia. Increased levels of granulocyte-macrophage colony-stimulating factor, interleukin 1, and tumor necrosis factor were seen in only one patient with sepsis.

Adult↗

Diagnostic and prognostic significance of serum and tissue trace elements in breast malignancy.

50 cases of breast malignancy constituted the study group. 26 age and sex matched formed the control group. Serum and tissue trace element viz copper, zinc, selenium and molybdenum levels were estimated by atomic absorption photometry. The study group showed significant hypercupremia and molybdenemia, hypozincaemia and hyposeleniamia. The reversal of trend was documented after therapy. The tissue level of copper and molybdenum was high and zinc and selenium was low. An association between serum and tissue level of trace element, stage, histological differentiation was observed. It was postulated that levels of trace elements may help in diagnosis and prognosis of disease.

Breast↗

Metabolic factors in the development of retinopathy of juvenile-onset type I diabetes mellitus.

Thirty-five patients of insulin-dependent diabetes mellitus (IDDM) were investigated for the effect of various metabolic factors on retinopathy. The severity of retinopathy increased with duration and age of onset of IDDM. Degree of glycaemia (fasting blood sugar, FBS) was similar in patients with or without retinopathy. All IDDM patients as a group showed severe carbohydrate intolerance with lower basal and post glucose serum immunoreactive insulin (IRI) levels and serum C-peptide radioimmunoreactivity (CPR) as compared to controls. The insulin secretory response was similar in no retinopathy, mild retinopathy and severe retinopathy groups. Patients with retinopathy had higher incidence of hyperlipidemia but mean serum levels of cholesterol and triglyceride were similar. This study does not suggest a direct relationship between the various metabolic factors studied and retinopathy due to IDDM.

Adult↗

Blood requirement and utilization in spinal surgery (blood in spinal surgery).

The blood requisition practice for the most commonly performed spinal prolapsed disc surgery was assessed in a prospective manner for 18 months, in total 108 patients. It was observed that nearly 78% operations did not require any transfusion. Transfusion index (TI) was .4, showing a tendency of over ordering of blood for these procedures. The cross match: transfusion (C/T) ratio was very high 4.3. It is obvious that these procedures hardly require blood transfusion. Thus by introducing an ABO-Rh typing screening and immediate spin cross match scheme, can drastically reduce the patients agony, laboratory work load and patients treatment cost.

Blood Transfusion↗

FK506 versus cyclosporine as primary immunosuppressive agent for orthotopic liver allograft recipients. Histologic and immunopathologic observations.

We investigated possible explanations for the common occurrence of perivenular lesions in liver allografts of patients on FK506 within a few weeks to several months after OLT. Hematoxylin and eosin-stained sections of pre- and postperfusion biopsy specimens and day 7 post-transplant protocol biopsy specimens from 31 patients, randomly assigned to either FK506 or CsA as primary immunosuppressive agent, were reviewed, and immunohistochemical stains for HLA-DR antigen and S-100 protein were performed by the avidin-biotin peroxidase complex method. The histologic features of cellular rejection in the portal tracts of day 7 posttransplant allograft biopsy specimens from patients on FK506 were milder than those from patients on CsA. Immunohistochemical stains for HLA-DR showed intense positivity in a variety of cell types in day 7 posttransplant specimens from both groups, including sinusoidal-lining cells, bile duct epithelial cells, vascular endothelial cells, inflammatory cells, and occasional injured hepatocytes. Although diffuse lobular staining was seen in the majority of cases in both groups, either with or without rejection, liver biopsy specimens from patients on FK506 showed concentration of positively stained cells in perivenular regions more often, and at a lower overall histologic grade of rejection, than specimens from patients on CsA. There were no differences in the number and distribution of S-100 protein-positive dendritic APC between biopsy specimens from FK506 versus CsA-treated patients, or between specimens with and without cellular rejection in either group. It is suggested that the development of perivenular injury, which is seen frequently in allograft biopsy specimens from patients on FK506 obtained at various intervals after transplantation, may be related to drug toxicity rather than to the process of allograft rejection.

Cyclosporine↗

Alprazolam modifies animal behaviour on elevated plus-maze.

Exposure to elevated plus-maze is known to evoke approach-avoidance conflict behaviour and anxiety related movements in mice. Alprazolam (0.1 to 1 mg/kg, ip) produced dose dependant increase in antianxiety response, 100% first preference to open arm, open arm entries and exploratory behaviour. This effect was not only comparable to diazepam but also sensitive to reversal by flumazenil, a benzodiazepine receptor antagonist. Withdrawal of alprazolam (2 mg/kg/day for 14 days) and diazepam (20 mg/kg/day for 14 days) from chronic treatment produced typical anxiety response in animals. When tested for transfer latency, a parameter for learning and memory, both diazepam and alprazolam interfered with cognitive behaviour. Besides these actions, alprazolam also possesses anti-depressant property which makes it an atypical benzodiazepine for anxiety, panic disorder and endogenous depression.

Alprazolam↗

Cellular deformability studies in leukemia.

This study was carried out to investigate the red blood cell and white blood cell deformability index in leukemia which is marked by an uncontrolled increase of leucocytes in the bone marrow as well in peripheral blood. It was observed that leucocytes are less deformable than erythrocytes, and erythrocytes from Chronic Myelogenous Leukemia (CML) patients less deformable than normal erythrocytes. The deformability indexes for lymphoblasts from acute lymphoblastic leukemia and myeloblasts from acute myelogenous leukemia were almost the same and higher than that of granulocytes from chronic myelogenous leukemia. These observations led to the conclusion that the significant increase in the resistance to the flow of blood in vivo in leukemia may be due to the increase in the number of leucocytes which are more rigid than erythrocytes.

Erythrocyte Deformability↗

Substantial urinary concentrations of material resembling beta-core fragment of chorionic gonadotropin beta-subunit in mid-menstrual cycle.

We measured the day-to-day variations in concentrations of beta-core, luteinizing hormone (LH), and alpha-subunit in urine during the menstrual cycle. The alpha-subunit concentrations showed a pattern similar to that of the LH concentrations. beta-Core-like material was increased during and up to 3 to 4 days after the surge in urine LH. The urine LH concentration was associated with the presence of beta-core immunoreactivity during the urine LH peak. Chromatography showed that, at the peak LH concentration and at 2 days after the LH peak, beta-core immunoreactivity could be accounted for by the presence of a peptide of low molecular mass similar to the beta-core molecule of hCG, but probably originating from the degradation of LH. The prolonged excretion of gonadotropin metabolites in the midcycle must be considered when beta-core is being assessed as a tumor marker.

Adult↗

Embryonic/fetal mortality after exposure to tritiated water in pregnant Swiss albino mice during different gestation periods.

Pregnant Swiss albino mice were given a priming injection(im) of tritiated water (HTO) at the dose rate of 2.3 and 5 microCi/ml body water (74, 111 or 185 KBq/ml body water) at 0, 6 and 14 day post conception (d.p.c.) and were subsequently maintained on tritiated drinking water ad libitum during preimplantation (0-5 d.p.c.), organogenetic (6-12 d.p.c.) or fetal (14-18 d.p.c.) period, respectively. On day 18 of gestation the females were sacrificed by cervical dislocation to record the implant sites per dam and embryonic/fetal mortality. Significant reduction was observed in average implant sites per dam when the females were exposed to any of the three doses during the preimplantation period due to embryonic resorption before implantation. However, the same was found to be within the normal range when mothers were exposed during the organogenetic or fetal period. Prenatal mortality (embryonic resorption/fetal death) was higher after in utero exposure to different doses during preimplantation period as compared to organogenetic period, but mortality did not occur after exposure to any of the doses during the fetal period. Occurrence of mortality was found to be dose dependent.

Animals↗