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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 793 records · Page 44Linked to original sources

The impact of postnatal depression on boys' intellectual development.

A follow-up study was carried out to investigate the children of 204 mothers who had previously participated in a study of their mental health during pregnancy and the first postnatal year. One hundred and seventy two children, 170 mothers, and 99 fathers were assessed when the children were 3 years 10 months. Boys of mothers depressed in the first year postpartum scored approximately 1 standard deviation lower on standardised tests of intellectual attainment than boys whose mothers were well that year. The difference was reliable even when behaviour during the test was controlled for, and general behavioural problems, birth weight, parental IQ measures of the family climate and home environment, mother-child interaction, and breast-feeding during infancy were taken into account.

Adult↗

Accumulation of 5-ethyl-2'-deoxyuridine and its 5,6-dihydro prodrugs in murine lung and its potential clinical application.

The accumulation of 5-ethyl-2'-deoxyuridine (EDU), (--)-trans-(5S,6S)-5-bromo-5-ethyl-6-methoxy-5,6- dihydro-2'-deoxyuridine [(5S,6S)-BMEDU], (+)-trans-(5R,6R) -5-bromo-ethyl-6-methoxy-5,6-dihydro- 2'-deoxyuridine [(5R,6R)-BMEDU], (+)-trans-(5R,6R)-5-bromo- 5-ethyl-6-ethoxy-5,6-dihydro-2'-deoxy- uridine (BEEDU), (+)-trans-(5R,6R)-5-bromo-5-ethyl-6-ethoxy -5,6-dihydro-5'-O-valeryl-2'deoxyuridine (VBEEDU) [formula: see text] and (+)-trans-(5R,6R)-5-bromo-5-ethyl-6-ethoxy-5, 6-dihydro-3'-5'-di-O-valeryl-2'-deoxyuridine [formula: see text] (DVBEEDU) in lung and other tissues was investigated in male Balb-C mice following intravenous injection of the corresponding 4-(14)C-labelled compounds. EDU showed a rapid distribution into liver and lung immediately after injection, and the overall levels of radioactivity in blood, liver and lung were similar. The distribution of radioactivity in lung after injection of [4-(14)C](5S,6S)-BMEDU and [4-(14)C]5R,6R)-BMEDU were substantially different from one another and also from that of[4(-14)C]EDU. The radioactivity level present in lung samples after injection of both (4-(14C](5S,6S)-BMEDU and [4-(14)C](5R,6R)-BMEDU was substantially higher than that in blood samples. Radioactivity levels present in lung samples taken at 18 min after injection of [4-(14)C]BEEDU were significantly higher (P < 0.05) than those for liver and blood samples. Although the radioactivity present in lung samples after injection of [4-(14)C]BEEDU did not provide a higher radioactivity level in lung samples than did [4-(14)C]BEEDU.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antibodies raised against the outer membrane protein interrupt adherence of enteroaggregative Escherichia coli.

Enteroaggregative Escherichia coli (EAggEC) is a distinct category of diarrheal pathogen implicated as the cause of persistent diarrhea. The pathogen exhibits a characteristic "stacked-brick" pattern of aggregation when incubated with HEp-2 cells. The outer membrane protein (OMP) profile of a prototype EAggEC strain (F03) reflected the presence of one major 30-kDa protein. The OMP is expressed in the presence of the 60-MDa plasmid that the strain harbors. Antibodies were raised against the OMP by injecting the protein into a rabbit. The manifestation of an adherence phenotype on HEp-2 cells was observed for F03 and other strains that express OMP in the presence and absence of anti-OMP serum. Clumps of bacteria forming an aggregative pattern were observed in the HEp-2 cell assay in the absence of OMP antibodies, whereas a few bacteria attached to the cells in the presence of OMP antibodies. Mannose-resistant hemagglutination of human erythrocytes observed in the presence of EAggEC strains was inhibited in the presence of anti-OMP serum. Sequence analysis of a peptide generated by protease digestion of OMP exhibited 90% homology to a peptide of flagellin protein encoded by the hag gene of Serratia marcescens. Immunolabeling of the outer membrane by colloidal gold confirmed the protein to be an OMP. Our results suggest that the OMP of EAggEC have common antigenic properties. Antibodies raised against the protein can prevent adherence in vitro and could potentially interrupt the natural disease.

Amino Acid Sequence↗

Calcium currents of ventricular cell pairs during action potential conduction.

We have studied the L-type calcium current that occurs during action potential conduction between an isolated pair of guinea pig ventricular cells. To accomplish this, we first recorded action potentials from the leader cell (stimulated cell, cell 1) and the follower cell (nonstimulated cell, cell 2) with a fixed coupling resistance between the cells supplied by a coupling clamp circuit. We then applied these recorded action potentials as command potential waveforms for other cells studied in the voltage-clamp mode in which internal and external solutions that isolated the L-type calcium current were used. The action potential waveform of the leader cell had a rapid upstroke and then a partial repolarization during the conduction delay before activation of the follower cell. The L-type calcium current occurred with a large magnitude during the conduction delay for the leader cell but not for the follower cell. This leads to an asymmetry of calcium current for the two cells, with greater calcium current for the leader cell than for the follower cell. When we reversed the direction of conduction for cell 1 and cell 2 by stimulating cell 2, we found that application of these recorded waveforms for the action potentials for cell 1 and cell 2 to the voltage-clamped cells also reversed the asymmetry of the magnitude of the calcium current. We conclude that discontinuous conduction in cardiac tissue is associated with a directionally determined asymmetry in the magnitude of the calcium current, with the leader cell experiencing a greater peak calcium current than the follower cell.

Action Potentials↗

1 alpha, 25-dihydroxyvitamin D3 receptor ontogenesis in fetal renal development.

We used immunohistochemical techniques to examine the distribution of 1 alpha, 25-dihydroxyvitamin D3 receptors (VDR) in developing rat and mouse kidneys and murine metanephric organ culture. In vivo, the patterns of expression in the two species were similar despite the slight difference in gestational periods (rat, 22 days; mouse, 19 days). Starting at gestational day 15, epitopes for VDR were found in cells of branching ureteral buds and in surrounding mesenchyme and at later developmental stages in glomerular visceral and parietal epithelial cells and proximal and distal tubules (DT). Epitopes for the 28-kDa calcium-binding protein (calbindin D28k) were found exclusively in DTs starting at gestational day 19. The pattern of VDR expression during in vitro nephrogenesis in serum-free murine metanephric organ culture paralleled that seen in vivo. At the time of explantation into organ culture (gestational day 13), VDR epitopes were not detected. By 3 days of in vitro development, VDR expression was identical to that found in gestational day 15 metanephroi in vivo. VDR expression after 5 days of in vitro development mirrored the pattern of gestational day 17 metanephroi in vivo. No calbindin D28k epitopes were seen at any in vitro developmental stage studied. We demonstrate for the first time that VDR are present in specific areas of the developing rat and mouse kidney early in gestation. Calbindin D28k appears later in developing rat and mouse kidney and is distributed differently than the VDR. Metanephric organ culture may be a useful model for studying the regulation and function of VDR during early renal development.

Animals↗

Absence of foramen transversarium in the human atlas vertebra: a case report.

Anatomical texts allude to many variations in the foramen transversarium of the seventh cervical vertebra, including its absence, but absent foramen transversarium of the atlas vertebra has not been mentioned. This is the case report of an atlas vertebra, the transverse process of which did not exhibit this foramen on the left side. However, the groove for the vertebral artery was present bilaterally on the posterior arch. The possible factors responsible for this interesting variant are discussed.

Adult↗

Immunolocalization of calcitriol receptor, plasma membrane calcium pump and calbindin-D28k in the cornea and ciliary body of the rat eye.

Epitopes of the calcitriol receptor, the ATP-dependent plasma membrane calcium pump (PMCA) and the 28-kD vitamin-D-dependent Ca-binding protein (calbindin-D28k) were detected in sections of the albino rat eye using light microscopy and immunohistochemistry of paraffin-embedded tissues. Calcitriol receptor and calbindin-D28k epitopes were detected in both the inner and outer layers of the ciliary body epithelium. PMCA was present in both epithelial cell layers of the ciliary body but was most prominent in the inner layer. Corneal epithelium and endothelium also contained epitopes for calcitriol receptor, PMCA and calbindin-D28k. These Ca-regulatory proteins may play a role in the cellular physiology of the albino rat eye by maintaining appropriate intracellular and aqueous humor Ca concentrations.

Animals↗

Effect of dermal application of hexachlorocyclohexane (HCH) on male reproductive system of rat.

1. The toxic manifestations of dermally applied hexachlorocyclohexane (50 mg or 100 mg kg-1 body weight day-1, 5 days in a week for 120 days) on testes and sperm of rat have been investigated. 2. The results indicate that exposure of HCH through the dermal route could lead to an alteration in the activities of marker testicular enzymes viz. sorbitol dehydrogenase (SDH), glucose-6-P-dehydrogenase (G6PDH), gamma-glutamyl transpeptidase (gamma-GT) and beta-glucuronidase (beta Gluc.) associated with specific cell types. 3. Significant quantities of HCH and its isomers accumulated in testes as well as sperm of treated rats. 4. HCH exposure also led to a decrease in serum testosterone levels, epididymal sperm count, sperm motility and an increase in the percentage of abnormal sperm. 5. These observations indicate the possibility of adverse effects of HCH on the male reproductive functions of men exposed dermally to this pesticide in industry or during spraying in the field.

Administration, Topical↗

Immuno-localization of the calcitriol receptor, calbindin-D28k and the plasma membrane calcium pump in the human eye.

Using immunohistochemical methods, we detected epitopes of the calcitriol receptor, the ATP-dependent plasma membrane calcium pump and the 28kD vitamin D-dependent calcium-binding protein in sections of the human eye. In retinal photoreceptors, vitamin D receptor, plasma membrane calcium pump and calcium-binding protein epitopes were detected in the outer nuclear layer. Epitopes for the vitamin D receptor and the calcium-binding protein were present in the inner and outer segments of the photoreceptors, where visual transduction occurs. All three proteins were detected in some cells of the ganglion cell layer, the inner nuclear layer, and the retinal pigment epithelium. Epitopes for these proteins also were noted in the ciliary body epithelium. VDR epitopes were seen in lens epithelium. Some immunostaining for VDR, PMCA and calbindin-D28k also was present in the endothelium and in the basal epithelium of the cornea. The presence of these proteins in several tissues of the human eye suggests that the proteins may play a role in the cellular physiology of the eye. Their exact functions in the eye remain undetermined.

Antibodies, Monoclonal↗

Neoadjuvant hormonal downsizing of localized carcinoma of the prostate: effects on the volume of normal tissue irradiation.

A prospective evaluation of neoadjuvant hormonal downsizing in patients with localized carcinoma of the prostate was undertaken to assess its effect on normal tissue irradiation. Twenty patients with stage T1 or T2 (A, B) carcinoma of the prostate received 3 months of Lupron prior to definitive radiotherapy. The volumes of the prostate, seminal vesicles, bladder, and rectum from both the pre- and posthormone treatment planning CT were entered onto a 3-D treatment-planning system. The treatment planning parameters were standardized to facilitate comparison of the pre- and posthormonal volumes. Following the three monthly injections of Lupron, the average volume of the prostate was reduced by 37%. As a consequence, the volume of the bladder receiving at least 40, 52, and 64 Gy was reduced by an average of 15, 18, and 20%, respectively. In addition, the volume of the rectum receiving at least 40, 52, and 64 Gy was reduced by an average of 13, 20, and 34%, respectively. In conclusion, in patients with localized prostate cancer, downsizing of the prostate resulted in a reduction in the volume of bladder and rectum receiving high radiation doses. This approach may result in an improvement in the therapeutic ratio by reducing the morbidity of treatment.

Adenocarcinoma↗

Herniation of the spinal cord. Case report.

Herniation of the spinal cord, or displacement of the cord outside the dura, is so rare that only 13 cases have been reported in the literature. The authors report a new case of spontaneous herniation of the spinal cord in a 38-year-old man who presented with lower left limb paresis and Brown-Séquard syndrome, with a T-8 sensory level. Displacement of the spinal cord was noted on computerized tomography following myelography and on magnetic resonance imaging. The herniated cord was confirmed at operation and reduced intradurally. Postoperatively, the patient showed complete neurological recovery. Based on a review of the literature, herniation of the spinal cord may be classified as spontaneous, iatrogenic, or traumatic. At cervical levels, the spinal cord has herniated into an iatrogenic pseudomeningocele located dorsally. At thoracic levels, spinal cord herniations were reported to be in a preexisting extradural arachnoid cyst located ventrally. The authors propose a pathogenesis for spinal cord herniation based on abnormal positioning of the spinal cord in the dural sleeve and the known anteroposterior movements of the cord that occur with cardiac and respiratory pulsations. The presence of a dural defect situated on the concavity of the spinal curvature is a prerequisite for this rare condition. As adhesions develop between the cord and the edges of the dural defect, cerebrospinal fluid pulsations push the cord into a preexisting cyst. The authors suggest modifying the classification by Nabors, et al., of spinal meningeal cysts to include this mechanism of spinal cord herniation. This diagnosis should also be considered in the differential diagnosis of myelopathy in the absence of a mass lesion.

Adult↗

Recombinant hemoglobins as blood substitutes: a biotechnology perspective.

Human hemoglobin can be produced in microbial and mammalian organisms using many different expression systems. It is anticipated that recombinant hemoglobins (or globin genes) will have many applications including as an infectious agent-free, inexpensive raw material for a red blood cell substitute, as a vehicle for expression or delivery of other biomolecules, and in gene therapy of inherited hemoglobinopathies. Recombinant expression, combined with site-directed mutagenesis, is facilitating the modification of the functional properties of hemoglobin. Although a functional hemoglobin molecule can be derived using many of the known expression systems, the choice of the production system for manufacturing depends on the scale, acceptable cost, and the associated environmental impact of the various processes. While the efficient bacterial production systems yield a modified, "surrogate" hemoglobin, the transgenic animal-derived product is virtually identical to the human erythrocyte-derived hemoglobin. Both the microbial fermentation, and the mammalian transgenic systems can be geared to produce the enormous quantities of hemoglobin expected to be required to meet the anticipated demand for a successful blood substitute in the future.

Animals↗

Extrapulmonary lymphangioleiomyomatosis and lymphangiomatous cysts in tuberous sclerosis complex.

OBJECTIVE: To describe the clinical manifestations, imaging findings, and histologic features of extrapulmonary lymphangioleiomyomatosis (LAM) in the tuberous sclerosis complex (TSC). DESIGN: We retrospectively reviewed institutional medical records since 1940 to identify patients with TSC and extrapulmonary LAM. MATERIAL AND METHODS: Of 403 patients with TSC, 3 had pulmonary and extrapulmonary LAM and retroperitoneal lymphangiomatous cysts. The clinical, imaging, and histologic features of these three patients were summarized, including analysis of biopsy specimens by conventional histology, immunohistology, radiolabeled ligand-binding assays, and tissue culture. RESULTS: The three young women had characteristic dermatologic findings of TSC and pulmonary LAM. Two patients were of normal intelligence, and one had a recent history of contraceptive use. All three patients had intra-abdominal lymphangiomatous cysts, uterine LAM, and renal angiomyolipomas. Renal and uterine biopsy specimens demonstrated positive immunostaining for melanoma-related antigens and expression of estrogen and progesterone receptors by ligand-binding assay and immunohistology. Cells cultured from LAM tissue of one of the patients exhibited a mitogenic response to estradiol. CONCLUSION: Clinically significant extrapulmonary LAM is a rare manifestation of TSC and may occur in women with this disease who also have pulmonary LAM. The clinical features of these patients confirm the importance of sex steroids in the development of these lesions. Immunohistochemical findings suggest that LAM and angiomyolipomas have a neuroectodermal origin. The development of lymphangiomatous cysts in these patients is probably due to smooth muscle proliferation in lymph vessels, which can result in lymphatic obstruction.

Abdominal Neoplasms↗

Cisplatin stimulates protein tyrosine phosphorylation in macrophages.

Cisplatin [cis-dichlorodiamine platinum (II)], a potent anti-tumor compound, stimulates immune responses by activating monocyte-macrophages and other cells of the immune system. The mechanism by which cisplatin activates these cells is poorly characterized. Since protein tyrosine phosphorylation appears to be a major intracellular signalling event that mediates cellular responses, we examined whether cisplatin alters tyrosine phosphorylation in macrophages. We found that cisplatin increased tyrosine phosphorylation of several proteins in peritoneal macrophages and in P388D1 and IC-21 macrophage cell lines. Treatment of macrophages with tyrosine kinase inhibitors, genestein and lavendustin A, inhibited cisplatin-stimulated protein tyrosine phosphorylation in macrophages. Macrophages treated with cisplatin also exhibit increased fluorescence with anti-phosphotyrosine-FITC antibody. These data indicate that protein tyrosine phosphorylation plays a role in cisplatin-induced activation of macrophages.

Animals↗

Induction of protein tyrosine phosphorylation in macrophages incubated with tumor cells.

The cellular and molecular interaction between monocyte/macrophage and tumor cells leading to macrophage activation is not clearly understood. Since protein tyrosine phosphorylation appears to be a major intracellular signalling event, we checked whether the tumor cells alter tyrosine phosphorylation of proteins in macrophages. We found that both L929 and Yac-1 tumor cells induced increased tyrosine phosphorylation of several polypeptides in peritoneal as well as P388D-1 and IC-21 macrophages. Macrophages co-cultured with tumor cells also showed increased fluorescence with anti-phosphotyrosine-FITC antibody. These observations suggest that increased tyrosine phosphorylation plays a role in tumor cell-induced activation of macrophages.

Animals↗

Pharmacokinetics and bioavailability of 5-ethyl-2'-deoxyuridine and its novel (5R,6R)-5-bromo-6-ethoxy-5,6-dihydro prodrugs in mice.

The pharmacokinetics and oral (po) bioavailability of 5-ethyl-2'-deoxyuridine (EDU) and its novel 5,6-dihydro prodrugs (+)-trans-(5R,6R)-5-bromo-5-ethyl-6-ethoxy-5,6-dihydro-2'-deoxyuridine (BEEDU) and (+)-trans-(5R,6R)-5-bromo-5-ethyl-6-ethoxy-5,6-dihydro-5'-O-valeryl-2'- deoxyuridine (VBEEDU) were determined in male Balb/C mice following intravenous and no administration of a 0.4 mmol/kg dose. EDU was eliminated from blood with a half-life of 35.2 +/- 4.2 min. The mean residence time (MRT) and the area under the blood vs. time curve (AUC) for EDU after iv injection were 45.1 +/- 11.7 min and 1.7 +/- 0.2 mumol.g-1.min, respectively. EDU showed a 49% bioavailability in male.Balb/C mice. The pharmacokinetic parameters and bioavailability of EDU were improved significantly upon administration of the 5,6-dihydro prodrugs BEEDU or VBEEDU. The AUC of EDU after a 0.4 mmol/kg iv dose of BEEDU was 2.1 +/- 0.3 mumol.g-1.min, which is substantially higher than that after iv injection of EDU. The half-life and MRT of EDU were increased to 251.9 +/- 30.2 min and 352.0 +/- 91.5 min, respectively, after injection of BEEDU. The po bioavailability of EDU, after administration of BEEDU, was increased almost 2-fold (81%), compared with that of EDU (49%). The AUC of EDU after iv injection of VBEEDU was 1.8 +/- 0.2 mumol.g-1.min. The half-life and MRT of EDU, the active metabolite of VBEEDU, were 106.0 +/- 23.2 min and 157.0 +/- 40.8 min, which are substantially higher than those for EDU after administration of EDU.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗