Biomedical subjects
Publications and source records attributed to M S Kumar.
A titania-supported ammonium salt of 12-molybdophosphoric acid has been synthesized, and the salt-support interaction, which enhanced the reaction rate, has been correlated with the activity of the catalyst in the ammoxidation of 2-methylpyrazine.
A rapid, simple, sensitive and selective spectrophotometric determination of nitrite using new diazotizing and coupling reagents is described. The method is based on a diazotization-coupling reaction between dapsone and iminodibenzyl in a hydrochloric acid medium. The molar absorptivity and Sandell's sensitivity were found to be 7.5 x 10(4) l mol(-1) cm(-1) and 0.000613 microg ml(-1), respectively. The interference effects of various cations and anions were also studied and reported. This method has been found to be applicable for the determination of nitrite in various water samples.
Membranous obstruction of vena cava (MOVC) is a common cause of hepatic venous outflow obstruction. Surgical procedures utilized to relieve symptoms carry a high morbidity and mortality. A patient who presented with gradual onset ascites and dilated, tortuous veins over the anterior abdominal wall and the back was found to have MOVC by inferior vena cavogram. Balloon dilatation of the obstruction was done successfully through a transvenous approach. Following this, the patient improved remarkably. The procedure is safe, effective and easy to perform. This balloon angioplasty provides alternative method for treatment of membranous obstruction of vena cava.
Regional distribution of gonadotropin-releasing hormone (GnRH)-like-, beta-endorphin (beta-end)-like-, and methionine-enkephalin (met-enk)-like-immunoreactivity was quantified across various regions of the central nervous system (CNS) of male and female goats by using highly specific radioimmunoassays. All the animals were sacrificed during the months of March through June (non-breeding season). Although the distribution of these three neuropeptides was similar to other mammalian species, species-specific gender differences in the levels of neuropeptides were noticed in the goat CNS. Highest levels of GnRH-like immunoreactivities were found in the hypothalamus. The hypothalamus of male goats exhibited significantly higher levels of GnRH-like immunoreactivities compared to female goats. Other regions exhibiting GnRH-like immunoreactivities included olfactory bulbs, preoptic and supraoptic regions, and mamillary bodies. Both beta-end- and met-enk immunoreactivities were detected in all selected regions of goat CNS, but highest levels of these opioid peptide-like immunoreactivities were limited to the forebrain regions of the goat. The supraoptic area of the female goats contained significantly higher levels of beta-end-like immunoreactivities than that of the male goats. Met-enk-peptide-like immunoreactivity also exhibited gender-specific differences in its content in some regions of the CNS. The male goats exhibited significantly higher levels of met-enk-like immunoreactivity in both the striatal and hypothalamic regions of the brain.
Epiphyseal fractures of the distal radius are common in children but those involving the distal ulna are rare. Distal ulna epiphyseal injuries are usually Salter-Harris type II and are usually reduced closed and held in plaster to produce good results. In this paper we describe a Salter-Harris type IV injury of the distal ulna epiphysis which required open reduction and internal fixation due to soft tissue interposition.
The success of strain improvement programme depends on the number of isolates that can be screened after mutagenic treatment. A technique to rapidly screen large number of high-yielding isolates was developed. The 'agar plug' method that utilizes the anti-fungal property of lovastatin to produce a zone of inhibition against Neurospora crassa was not only economical but also less labour-intensive. We were able to isolate a high-yielding strain, the productivity of which increased by 138% as compared to the parent strain in the submerged fermentation process.
Transplantation of progenitor cells for regeneration of islet cells could prove invaluable in the treatment of diabetes mellitus. This study provides evidence that in rats maintained on a copper-deficient diet containing the copper-chelating agent tetraethylenepentamine pentahydrochloride, regeneration of single alpha and beta endocrine cells in the ductules and acinar tissue of the adult rat pancreata occurred. These regenerated cells both in the ductules and acinar tissue stained positive for glucagon and insulin similar to cells within the islets and in addition to being reactive to proliferative cellular nuclear antigen, an intracellular marker of active proliferation. In contrast, the control group pancreata did not show any evidence of islet regeneration, proliferation, or proliferative cellular nuclear antigen reactivity pre- or posttransplantation. Transplantation of digested pancreatic tissues from the copper-deficient group into the spleen of syngeneic diabetic rats reversed diabetes, and this was confirmed histologically by demonstrating cells within ductules that stained positively for insulin. This study concludes that copper deprivation contributes to the neogenesis of pancreatic alpha and beta cells in the ductules and acinar tissue of adult pancreas in rat model and that transplanted stem cells maintain their functional capacity in the recipient after transplantation.
OBJECTIVE: To correlate substance P content of synovial fluid with prostaglandin E2 content, radiographic evidence of joint abnormality, and anatomic location of the joint for normal and osteoarthritic joints of horses. SAMPLE POPULATION: Synovial fluid from 46 normal joints in 21 horses and 16 osteoarthritic joints in 10 horses. PROCEDURE: Normal and osteoarthritic joints were identified by clinical and radiographic examination, by response to nerve blocks, during scintigraphy or surgery, or by clinicopathologic evaluation. Substance P and prostaglandin E2 contents of synovial fluid were determined by radioimmunoassay. Radio-graphs of joints were assigned a numeric score reflecting severity of lesions. Joints were assigned a numeric score reflecting anatomic location. RESULTS: Median concentrations of substance P and prostaglandin E2 were significantly increased in osteoarthritic joints, compared with normal joints. A significant correlation was found between concentrations of substance P and prostaglandin E2 in synovial fluid, but a correlation was not detected between substance P concentration in synovial fluid and anatomic location of the joint or between radiographic scores of osteoarthritic joints and concentrations of substance P or prostaglandin E2. CONCLUSIONS AND CLINICAL RELEVANCE: A correlation existed between concentrations of substance P and prostaglandin E2 in synovial fluid obtained from normal and osteoarthritic joints. However, content of substance P in synovial fluid cannot be predicted by the radiographic appearance of the joint or its anatomic location. Substance P and prostaglandin E2 may share an important and related role in the etiopathogenesis of osteoarthritis, lending credence to the importance of neurogenic inflammation in horses.
BACKGROUND: Long-term renal transplant function is limited primarily by a progressive scarring process loosely termed "chronic rejection, chronic allograft nephropathy, or allograft fibrosis." Although the etiology of transplant fibrosis is uncertain, several possible factors including chronic cyclosporin A (CsA) exposure may contribute to its pathogenesis. CsA stimulates renal fibrosis perhaps through the induction of the potent pro-sclerotic growth factor, transforming growth factor beta (TGFbeta). Previously, we demonstrated that, in human transplant biopsies, acute CsA toxicity but not acute tubular necrosis is associated with elevated levels of renal TGFbeta protein. We now examine whether long-term CsA treatment (>1 year) is associated with elevated levels of intra-allograft TGFbeta and whether heightened expression of TGFbeta is clinically significant. METHODS: Using immunohistochemical techniques, we determined the relative level of expression of intrarenal TGFbeta protein in transplant biopsies. We studied biopsies obtained from 40 CsA-treated patients that were diagnosed as having chronic allograft fibrosis. Biopsies were scored as having minimal or high levels of TGFbeta. RESULTS: Seventy-two percent of patients expressed high levels of intra-allograft TGFbeta. This group of patients lost renal function at an average rate of -19.5+/-17.3 ml/min/year. In contrast, patients with minimal or no TGFbeta expression experienced a decline of only -6.2+/-4.1 ml/min/year (P=0.01). CONCLUSIONS: These results suggest that the majority of CsA-treated patients with biopsy proven chronic fibrosis have elevated levels of intra-graft TGFbeta that correlates with an increased rate of decline in renal function.
BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem-cell disorder in which the affected cells are deficient in glycosylphosphatidylinositol (GPI)-anchored proteins. Paroxysmal nocturnal hemoglobinuria is frequently associated with aplastic anemia, although the basis of this relation is unknown. OBJECTIVE: To assess the PNH status of patients with diverse marrow failure syndromes. DESIGN: Correlation of cytofluorometric data with clinical features. SETTING: Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland. PATIENTS: 115 patients with aplastic anemia, 39 patients with myelodysplasia, 28 patients who had recently undergone bone marrow transplantation, 18 patients with cancer that was treated with chemotherapy, 13 patients with large granular lymphocytosis, 20 controls who had received renal allografts, and 21 healthy participants. INTERVENTION: Patients with aplastic anemia, myelodysplasia, or renal allografts received antithymocyte globulin. MEASUREMENTS: Flow cytometry was used to assess expression of GPI-anchored proteins on granulocytes. RESULTS: Evidence of PNH was found in 25 of 115 (22%) patients with aplastic anemia. No patient with normal GPI-anchored protein expression at presentation developed PNH after therapy (n = 16). Nine of 39 (23%) patients with myelodysplasia had GPI-anchored protein-deficient cells. Abnormal cells were not detected in patients with constitutional or other forms of bone marrow failure or in renal allograft recipients who had received antithymocyte globulin. Aplastic anemia is known to respond to immunosuppressive therapy; in myelodysplasia, the presence of a PNH population was strongly correlated with hematologic improvement after administration of antithymocyte globulin (P = 0.0015). CONCLUSIONS: Flow cytometric analysis is superior to the Ham test and permits concomitant diagnosis of PNH in about 20% of patients with myelodysplasia (a rate similar to that seen in patients with aplastic anemia). The presence of GPI-anchored protein-deficient cells in myelodysplasia predicts responsiveness to immunosuppressive therapy. Early emergence of GPI-anchored protein-deficient hematopoiesis in a patient with marrow failure may point to an underlying immune pathogenesis.
Identification of the regulators of smooth muscle specific gene expression is critical for understanding smooth muscle cell (SMC) differentiation and the alterations in SMC phenotype seen in vascular diseases. Previous studies have identified that a 2-bp mutation in a conserved cis-acting element (TGTTTATC) in the promoter of the chicken smooth muscle (SM) alpha-actin gene abolished nuclear factor binding and decreased transcriptional activity of a 271-bp SM alpha-actin promoter fragment when transfected into rat aortic SMC. However, the promoter region containing this conserved sequence has negative cis regulatory activity when studied in homologous systems. The goal of the present studies was to further characterize the transcriptional activity of the rat SM alpha-actin promoter region between -224 and -236 that is conserved across mammals. DNAse I analysis and electrophoretic mobility shift assays demonstrated that SMC nuclear proteins bound an extended sequence (TGTTTATCCCCATAA). Transient transfection experiments of wild-type and mutant rat SM alpha-actin promoter-luciferase constructs into rat aortic SMC revealed that promoter activity was enhanced by mutations of specific nucleotides in the TGTTTATCCCCA region. Interestingly, the TGTTTATCCCCA element in the rat SM alpha-actin promoter is centered between 2 canonical E-boxes. Mutations of the flanking E-boxes abolished the enhancement in promoter activity seen with mutation of the TGTTTATCCCCA element alone. Thus studies provide evidence for a regulatory cassette in the rat SM alpha-actin promoter that regulates gene expression via combinatorial interactions between 2 E-boxes and a newly described TGTTTATCCCCA element.
Effects of acute exposure (2 hr) to either 1.5% halothane or 0.5% methoxyflurane were investigated in the Sprague Dawley rat. Pituitary (PIT) and central nervous system (CNS) substance P (SP)-like and beta-endorphin (beta-end)-like immunoreactivities were evaluated immediately after anesthetic exposure (2 h), after righting reflex (4 h) or 24 hr postexposure (24 h). Only halothane significantly reduced SP-like immunoreactivity in olfactory bulbs in both the 2-h and 4-h groups. Halothane elevated SP-like immunoreactivity of hippocampus at all three time periods, and in the hypothalamus at 2 h. Both anesthetics significantly depleted thalamic concentrations of SP-like immunoreactivity. Methoxyflurane anesthesia resulted in a drastic decrease in SP-like immunoreactivity in PIT at all three time periods periods, while halothane elevated PIT concentrations of this peptide at 4 h. Both anesthetics significantly decreased beta-end-like immunoreactivity in the olfactory bulbs and thalami at 2, 4, and 24 h. However, halothane alone significantly elevated beta-end-like immunoreactivity in the spinal cord at 24 h. Halothane significantly elevated PIT beta-end-like immunoreactivity at 2 and 24 h, while methoxyflurane significantly lowered it in the 4-h group, but elevated the levels of the same in the 24-h group. Brain stem beta-end immunoreactivity were significantly reduced at 2 h by both anesthetics, and at 4 h by methoxyflurane. Results indicate that halothane and methoxyflurane may differ significantly in their actions on SP and beta-end secreting neurons in the CNS.
Several 7-(3R,4R-N,N'-dialkyl diaminopyrrolidinyl)-substituted quinolones were synthesized and evaluated for antibacterial activities. 5-Amino-7-(3R,4R-N,N'-dimethyldiamino-6,8-difluoro-1,4-dihydro-1-c yclopropyl -4-oxoquinoline-3-carboxylic acid was found to have potent antibacterial activity against gram +ve organisms.
BACKGROUND: Traditionally, elderly donor kidneys have not been widely accepted for transplantation on the assumption of inferior performance. However, the United Network for Organ Sharing reports an increase in the number of elderly donors from less than 2% in 1982 to 24% in 1995. This trend is commensurate with the increase of older dialysis patients and an overall increase in the elderly population in the United States (1). Optimal utilization of these kidneys is essential to overcome the acute organ shortage. METHODS: In this study, we transplanted 25 kidneys from elderly donors (ages 56-72 years) into young adult recipients (ages 20-50 years) (group 1) over a 4-year period. We compared the results with matched recipients of young adult donor kidneys (group 2) with regard to long-term kidney function and graft survival. A pretransplant biopsy of elderly donor kidneys was carried out and a frozen section report was obtained. Only those kidneys showing glomerulosclerosis of less than 20% were accepted for transplantation. All cadaveric kidneys were preserved in University of Wisconsin solution. RESULTS: Pretransplant biopsies of elderly donor kidneys showed structural deficits, which included glomerulosclerosis in 85%, arteriolar and/or mesangial thickening in 75%, and interstitial lymphocyte infiltration in 30%. The mean serum creatinine was 2.4+/-0.74, 2.2+/-0.56, and 2.9+/-0.76 mg/100 ml in group 1 and 1.5+/-0.55, 2.3+/-2.24, and 1.7+/-0.62 in group 2 at 1, 3, and 5 years, respectively. The patient survival was 92%, 92%, and 88% in group 1, and 100%, 100%, and 100% in group 2 at 1, 3, and 5 years, respectively. The graft survival was 80%, 64%, and 56% in group 1 and 100%, 96%, and 88% in group 2 at similar time intervals. The differences in the serum creatinine and graft survival between the two groups were statistically significant (P < 0.05). CONCLUSIONS: Most of the elderly donor kidneys with structural deficits transplanted into young adults provided suboptimal function and inferior long-term graft survival. To maximize the utilization and optimize the survival of elderly donor kidneys, we propose transplantation of these kidneys into age-matched recipients with similar physiological requirements as those of donors, with regard to kidney function.
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The effects of nitrous oxide (N2O) on steady-state concentrations and turnover rates of catecholamines in the olfactory bulb, hypothalamus, brain stem, hippocampus, striatum, thalamus, cerebral cortex, and spinal cord were determined in rats. Animals were exposed for 2 h to either 60% N2O or air. Immediately following exposure, all animals were injected intraperitoneally with alpha-methylparatyrosine (alphaMPT), a competitive inhibitor of tyrosine hydroxylase, and sacrificed at 0, 30, or 90 min postinjection. Brain catecholamine concentrations were determined using high-performance liquid chromatography coupled with electrochemical detection (HPLC-EC). Results indicate that N2O exposure significantly elevates steady-state concentrations of norepinephrine (NE) in the hypothalamus and striatum yet decreases amine levels in the brain stem region. Steady-state levels of dopamine (DA) were not significantly altered in any region of the CNS by N2O exposure. Acute exposure to N2O also resulted in significant decreases in the turnover rate of NE in the brain stem, yet it increased turnover of this amine in the olfactory bulb, hypothalamus, and striatum. Acute exposure to N2O resulted in a decreased turnover rate of DA in the hippocampus and striatum. In contrast, N2O appears to increase DA turnover in the olfactory bulb. These results indicate that acute exposure to N2O in rats causes region-specific alterations in steady-state levels and turnover rates of DA and NE within the central nervous system.
Effects of acute exposure (2 h) to either 1.5% halothane or 0.5% methoxyflurane on chemical mediators of the hypothalamic-pituitary-adrenal (HPA) axis were evaluated in male Sprague-Dawley rats immediately after exposure, after the righting reflex (4 h), or 24 h postexposure. Effects of these anesthetics on hippocampal corticotropin releasing factor (CRF) were also evaluated. Methoxyflurane caused significant elevations in pituitary adrenocorticotropin hormone (ACTH)-like immunoreactivities in all three of the experiment's time groups, yet halothane failed to cause the same response immediately after exposure. Serum ACTH-like immunoreactivities were significantly elevated immediately after exposure to both anesthetics, but were not elevated at 4 and 24 h postexposure. Corticosterone (CORT)-like immunoreactivities were significantly elevated by halothane in all experimental groups, and in the 2- and 24-h groups following methoxyflurane exposure. Hippocampal CRF-like immunoreactivities remained unaffected by either anesthetic. Results indicate that a 2-h exposure to either halothane or methoxyflurane results in significant activation of the rat hypothalamic-pituitary-adrenal axis, and that the activation appears to be sustained over a 24-h period.
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