Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 901 records · Page 50Linked to original sources

PubMed1993

An enzyme linked immunosorbent assay for detection of anti-aorta antibodies in Takayasu arteritis patients.

Thirty cases of clinically and angiographically proven non-specific aortoarteritis with appropriate controls were studied. Antiaorta antibody titres were estimated using enzyme linked immunosorbent assay (ELISA) method. The controls included patients of vascular diseases other than non-specific aortoarteritis, autoimmune diseases (rheumatoid arthritis and systemic lupus erythematosis), and normal healthy individuals. An absorbance value at 492 nm at a dilution of 1:500 of patients' sera was expressed as the antiaorta antibody titre. There was a significant difference (P < 0.005) between the mean value of the antibody titre of non-specific aortoarteritis patients (0.471 +/- 0.073) and patients of other vascular diseases (0.209 +/- 0.056), autoimmune disease patients (0.143 +/- 0.024) and controls (0.108 +/- 0.012). Collagenase treatment of the aorta resulted in the fall of the antibody titre of aortitis patients (0.162 +/- 0.036) suggesting that the collagen might be one of the components responsible for autoantigenecity of the aorta resulting in aortitis. The precise nature of the antigen needs to be identified.

Adolescent↗

PubMed1993

Vitamin D and adaptation to dietary calcium and phosphate deficiencies increase intestinal plasma membrane calcium pump gene expression.

The effect of vitamin D and other variables on the synthesis of the chicken intestinal plasma membrane calcium pump (PMCA) mRNA was assessed. The DNA probe for Northern analysis was obtained by reverse transcription and PCR with intestinal poly(A)+ RNA, using two 20-mer oligonucleotide primers homologous to the 3' coding region of the human teratoma PMCA. An EcoRI restriction fragment of the PCR product was cloned into the pBluescript II KS(-) phagemid vector, and the chimeric plasmid was used to transform Escherichia coli. The amino acid sequence deduced from the nucleotide DNA sequence of the PCR product and the cloned DNA were 96% homologous with the teratoma sequence. Northern blots of intestinal poly(A)+ RNA with 32P-labeled DNA showed the presence of three major species of chicken PMCA mRNAs at about 6.6, 5.4, and 4.5 kb. Northern analysis with the chicken PMCA DNA indicated that repletion of vitamin D-deficient chickens with vitamin D increased PMCA mRNAs in the duodenum, jejunum, ileum, and colon. After injection of 1,25-dihydroxyvitamin D3 intravenously into vitamin D-deficient chickens, duodenal PMCA mRNA tended to increase by 2 hr, reached a maximum at about 16 hr, and returned to baseline levels at 48 hr. Adaptation of chickens to either a calcium- or phosphorus-deficient diet resulted in a 2- to 3-fold increase in duodenal PMCA mRNA. These results indicate that vitamin D and specific variables that affect calcium absorption through the vitamin D-endocrine system increase intestinal PMCA gene expression.

Amino Acid Sequence↗

PubMed1993

Molecular cloning of a plasma membrane calcium pump from human osteoblasts.

The osteoblast plays a critical role in bone formation, bone remodelling, bone matrix formation, and matrix calcification. To better understand the process of osteoblast-controlled bone formation, we determined the structure and isoform types of the plasma membrane calcium pump from normal human osteoblasts. A complementary DNA library from normal human osteoblasts was screened for plasma membrane calcium pump clones. Sequencing and analysis of cDNA clones revealed the presence of a 3986 base pair cDNA that encoded a 1220 amino acid protein that was similar to the human plasma membrane calcium pump isoform 1. Polyadenylated RNA from human osteoblast cells contains bands of RNA approximately 5050 and 6750 bases long. Reverse transcription of polyadenylated RNA from human osteoblasts followed by amplification of the RNA-DNA duplex with calcium pump isoform-specific primers revealed the presence of isoforms 1 and 2 of the calcium pump. Isoform 4 was not detected. We conclude that normal adult human osteoblasts contain a plasma membrane calcium pump that is similar to the human plasma membrane calcium pump isoform 1. It is likely that this pump plays an important role in the cell biology of the human osteoblast.

Adult↗

PubMed1993

Endothelin-stimulated human monocytes produce prostaglandin E2 but not leukotriene B4.

The activation and proliferation of a prostaglandin E2 (PGE2) producing monocyte/macrophage may play a major role in down-regulating immune function after injury. But the mechanism by which monocyte or macrophage activation occurs in injury is unknown. Endothelin is a 21-amino acid peptide produced by vascular endothelium in response to ischemia, injury, or endotoxin. Prior work from our laboratory has shown that endothelin increases intracellular calcium in monocytes and causes production of interleukins-6 and -8. In the data reported in this paper, 10(-9) M endothelin stimulated human monocytes to produce 1050 +/- 63 pg/ml of PGE2 at 6 hr and 1328 +/- 47 pg/ml at 24 hr. This was nearly as much PGE2 production as that by bacterial lipopolysaccharide (endotoxin) stimulation (1295 +/- 47 pg/ml at 6 hr and 1506 +/- 94 at 24 hr). Endothelin had no effect on production of leukotriene B4. Endothelin may play an important initiating role in post-traumatic immunosuppression.

Dinoprostone↗

PubMed1993

Characterization of the G serotype and genogroup of New Delhi newborn rotavirus strain 116E.

We recently reported that the culture-adapted neonatal rotavirus strain 116E represented the first P type 11 human rotavirus, based on the close relationship of its VP4 protein to that of the bovine serotype G10P11 strain B223. In this study, we demonstrated by sequence analysis and cross-neutralization studies that the VP7 protein of 116E is closely related to those of the human serotype G9 strains, F45 and WI61, but distinct from B223 and other rotaviruses. Low-level cross-neutralization was also observed between strains 116E and B223, probably because of the antigenic similarity of their VP4 proteins. We have demonstrated by RNA-RNA hybridization that strain 116E is a reassortant between strains from the Wa and bovine (KK3-like) genogroups, deriving at least seven genes from the former and at least one gene from the latter. Together with the recent identification of serotype G10P11 newborn rotavirus strains in Bangalore, India (M. Das et al., Virology, 194, 374-379, 1993), these results are consistent with the hypothesis that reassortment may be an important mechanism for generation of rotavirus strains of newborns.

Amino Acid Sequence↗

PubMed1993

RNA editing of a chimeric maize mitochondrial gene transcript is sequence specific.

RNA editing was analysed in the mitochondrial ATPase complex subunit 6 gene (atp6) transcripts of the C male-sterile cytoplasm (cms-C) of maize. The only copy of atp6 in cms-C, designated C-atp6, is a triple gene fusion product comprised of DNA sequences derived from atp9, atp6, and an unknown origin. Sequences of cDNAs revealed 19 C to U alterations resulting in 16 amino acid residue changes compared to the genomic sequence. The only C to U edit in the 39-nucleotide sequence similar to atp9 was comparable to a change in the complete atp9 mRNAs of Petunia, Oenothera, wheat, and sorghum. The 442 nucleotides of unknown origin were not edited. The 18 editing events within the atp6 homologous region were similar to those in the atp6 transcripts of sorghum. RNA editing in maize C-atp6 transcripts introduces a translational stop codon at the same position where it is created by editing in sorghum and Oenothera atp6 mRNAs and is already present in atp6 open reading frames of most other plant and non-plant organisms. Our results, along with other reports on editing in chimeric transcripts, indicate that RNA editing is not influenced by rearrangements but instead is sequence specific.

Adenosine Triphosphatases↗

PubMed1993

Ophthalmic manpower in India--need for a serious review.

An attempt has been made to estimate the number of ophthalmic surgeons (OSs) in India, their distribution amongst the constituent states/union territories, and imbalances in the urban (big and small cities) and rural areas. With an ophthalmic surgeon:population ratio of 1:107,000 (similar to that in the UK), an increasing amount of blindness in India, the output by ophthalmic surgeons continues to be low. Whereas the shortage of surgeons has been recognised as a critical problem by the National Programme for Control of Blindness, recommendations made at various forums have been restricted only to increasing production of existing surgeons. The key issues relating to OSs in India are uneven distribution, under utilisation and increasing demands on the ophthalmologist's time, due to advancement in clinical ophthalmology in recent years. Serious intervention to streamline distribution and improve utilisation of OSs in government and private sectors is necessary to effectively counter the current menace of blindness. Another option-creating an exclusive cadre of cataract surgeons trained to perform intracapsular cataract extraction (ICCE) for a period of four months in the medical colleges--has been recommended.

Blindness↗

PubMed1993

Caffeine-derived N-nitroso compounds. III: Mutagenicity in S. typhimurium and in vitro induction of DNA single-strand breaks in rat hepatocytes by mononitrosocaffeidine and dinitrosocaffeidine.

Mutagenesis in S. typhimurium and in vitro induction of DNA single-strand breaks in primary rat hepatocytes (DNA-SSB) have been investigated for two new N-nitroso compounds, mononitrosocaffeidine (MNC) and dinitrosocaffeidine (DNC). Mononitrosamidocaffeidine (MNAC) and tert.-(butyloxy)carbonyl-mononitrosamidocaffeidine (t-BOC-MNAC), both nitrosated derivatives of caffeidine with nitrosation at methylcarboxamide-N only, were also similarly studied. MNC, an asymmetric nitrosamine, failed to show mutagenicity in any of the tester strains used, and also did not induce DNA-SSB in rat hepatocytes. DNC, having both N-nitrosamide and N-nitrosamine groups in the molecule, showed direct mutagenicity in TA100, TA1535 and TA102. The mutagenic potential of the compound was found to increase on S9 activation. However, it was non-mutagenic in TA98 and TA1537. DNC also exhibited a high potential for inducing alkali-labile DNA-SSB in rat hepatocytes (70-78% C-T value) and was cytotoxic at concentrations over 0.1 mumole/ml. Both MNC and DNC were found to produce formaldehyde on S9 activation. MNAC was not mutagenic directly but showed weak mutagenicity on metabolic activation, whereas t-BOC-MNAC was mutagenic both with and without S9 activation in TA100, TA1535 and TA102. t-BOC-MNAC was more cytotoxic to hepatocytes than MNAC, though both caused DNA-SSB to the same extent (62% C-T value). On the basis of the presented data it is inferred that while DNC is a direct-acting mutagen in TA100, TA1535 and TA102 due to the presence of a reactive N-methylnitrosamido group, its mutagenic potential is greatly enhanced in the presence of S9 possibly due to the synergistic influence of an activated N-methylnitrosamino group in the molecule. Additionally, the study shows a qualitative consistency between Salmonella mutagenicity, genotoxicity in hepatocytes and the reactivity of the methyl group at the nitrosamido-N in nitrosated caffeidine compounds.

Animals↗

PubMed1993

Effect of in vivo administration of cisplatin on the colony forming ability of murine bone marrow cells.

In vitro colony forming ability of bone marrow cells obtained from cisplatin-treated C3H/He mice was studied. Mice were administered cisplatin in a single intraperitoneal dose of 10 mg/kg body wt, 24 h prior to the harvest of femoral bone marrow cells. Incubation of untreated bone marrow cells without any CSF in vitro showed little colony forming ability which was marginally enhanced in cisplatin-treated bone marrow cells. Presence of M-CSF (250 U/ml) or GM-CSF (250 U/ml) in the culture medium significantly augmented the colony forming ability of both untreated and cisplatin-treated bone marrow cells. In the presence of M-CSF, colony forming units-macrophage (CFU-M) were predominantly high in untreated bone marrow cells, followed with CFU-granulocyte-macrophage (CFU-GM). The number of CFU-M was significantly up-regulated in response to M-CSF in bone marrow cells obtained from cisplatin administered mice, whereas the number of CFU-GM remained unchanged, as compared to untreated mice. Both CFU-M and CFU-GM were enhanced in the presence of GM-CSF in untreated bone marrow cells. Cisplatin-treated bone marrow cells on incubation in the presence of GM-CSF showed a significant enhancement of CFU-M and GM as compared to untreated samples. IL-1 (100 U/ml) in the presence of M-CSF significantly up-regulated colony forming ability of cisplatin-treated bone marrow cells, whereas TNF (100 U/ml) inhibited the colony forming ability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Neuroendocrine and psychosocial mechanisms in post-partum psychosis.

(1) Results from a study investigating psychosocial and neuroendocrine influences on post-partum psychosis are presented. Subjects were 43 pregnant women with histories of affective disorder (bipolar or schizoaffective disorder, n = 26; major depressive disorder, n = 17), together with 45 pregnant women without any psychiatric history. (2) At 36 weeks antenatal assessments were carried out of the women's psychiatric histories, current psychiatric state and also the occurrence of life events in the preceding year. They were then monitored for 6 months after delivery during which time psychiatric state and any further life events were recorded. Illness was defined according to Research Diagnostic Criteria (RDC); 22 high risk women and 3 control women were categorised as RDC 'cases' during the post-partum follow-up period. Fifteen of the bipolar/schizoaffective women (8 of whom subsequently became ill within 3 months of delivery) and 15 controls (all of whom remained well) also participated in a neuroendocrine test at 4 days post-partum when their growth hormone response to a challenge dose of the dopamine agonist, apomorphine, was measured. (3) The results showed that women with histories of depression and control women who became ill after delivery were three times more likely to have had a life event in the year preceding onset of illness than women from these subgroups who remained well. In contrast, for women with histories of bipolar or schizoaffective disorder, life events appeared to be unimportant. Instead bipolar/schizoaffective women who became ill showed an enhanced growth hormone response to the apomorphine challenge test compared to those who remained well and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Vasopressin receptor-mediated endocytosis in cells transfected with V1-type vasopressin receptors.

We examined the process of receptor-mediated endocytosis in A-9 lung fibroblast and chinese hamster ovary (CHO) cells transfected with the recently cloned vasopressin V1a receptor (51). We used a fluorescent labeled vasopressin analog (rhodamine-mercaptopropionic acid lysine vasopressin) and radiolabeled vasopressin to examine this process in the two transfected cell lines. Both A-9 and CHO cells internalize vasopressin in a manner consistent with receptor-mediated endocytosis. A-9 cells internalize vasopressin more rapidly than CHO cells. The process is inhibited by vasopressin and by specific vasopressin V1 receptor antagonists but not by specific V2 receptor antagonists. Hypertonic sucrose inhibits endocytosis in both cell types suggesting a role of clathrin coated pits in the endocytosis of receptor in these cells. These cells are excellent models in which to examine the effect of receptor mutations on vasopressin receptor-mediated endocytosis.

Animals↗

PubMed1993

Perioperative prophylaxis of venous thromboembolism.

Venous thromboembolism is an important cause of morbidity and mortality in hospitalized patients, causing 100,000 to 200,000 deaths per year in the United States. Patients undergoing surgery are at the highest risk of venous thromboembolism. The magnitude of this risk in a patient depends on the surgical procedure performed and the presence of other risk factors that predispose to venous thromboembolism. The clinical diagnosis of both deep vein thrombosis and pulmonary embolism is notoriously inaccurate. Furthermore, two thirds of all fatal pulmonary emboli cause death within 30 minutes of the embolic episode, leaving little time for diagnostic work-up and effective treatment. Prophylactic treatment for prevention of venous thromboembolism is therefore important in these patients, and several effective mechanical and chemical methods for this purpose are available. The pathogenesis of deep vein thrombosis in the surgical patients, the predisposing risk factors, and the available prophylactic modalities are discussed in this article. Recommendations for the use of various approaches in different risk categories are provided.

Humans↗

PubMed1993

Evaluation of the fluorescence actin staining test for detection of enteropathogenic Escherichia coli.

Enteropathogenic Escherichia coli (EPEC) strains designated on the basis of their serotypes are epidemiologically associated with diarrhea. They adhere to the intestinal mucosa, producing the characteristic attaching and effacing (AE) lesion in an in vitro organ culture system. EPEC manifest localized adherence (LA) in the HEp-2 cell assay, and this is commonly used for clinical diagnosis. Recently, the fluorescence actin staining (FAS) test was proposed for the identification of E. coli causing the AE lesion. We therefore compared the FAS test with the HEp-2 cell assay and the EPEC adherence factor (EAF) probe assay for the detection of EPEC strains. Among 240 stool samples from children with diarrhea examined, 176 yielded E. coli and 14 of these strains showed the LA pattern in the HEp-2 cell assay; 11 of these were positive by both the EAF and the FAS tests. By using the HEp-2 cell assay as the "gold standard," the FAS test gave a sensitivity of 78.5% and a specificity of 100%. The three localized adherent FAS-negative strains tested subsequently were positive by the enteroaggregative E. coli DNA Probe and failed to produce the AE lesions characteristic of EPEC. When these strains were not considered, the sensitivity of the FAS test for detecting isolates that manifest LA was 100%. Against the EAF probe, the sensitivity and specificity of the FAS test were 91.6 and 100%, respectively. The FAS test avoids infrequent but nevertheless important phenotypic misclassifications in the HEp-2 cell assay, and it may therefore serve as a confirmatory test for EPEC.

Actins↗

PubMed1993

Postnatal decrease in muscarinic cholinergic influence on Ca2+ currents of rabbit ventricular cells.

We have studied developmental changes in the muscarinic cholinergic modulation of L-type Ca2+ current (ICa) in enzymatically isolated adult and newborn (1-4 days old) rabbit ventricular cells using the whole-cell patch-clamp method. Carbachol (10 microM) caused a 2.8-fold increase in the half-maximal concentration (EC50) for isoproterenol to stimulate ICa for adult cells compared with the control with little effect on the maximal ICa density (Imax), whereas the stimulatory effect of isoproterenol on newborn ICa was completely eliminated by 10 microM of carbachol and was decreased by 40% at 0.1 microM carbachol. Carbachol increased the EC50 for forskolin to stimulate ICa 2.9-fold for adult cells and 7.3-fold for newborn cells with little effect on the Imax for either group. 5'-Guanylyl imidodiphosphate [Gpp(NH)p; 100 microM] reduced the stimulatory effect of 0.1 microM isoproterenol on adult ICa (percent increase over predrug level) by a factor of 1.8 compared with the control (400 microM guanosine triphosphate), whereas the isoproterenol effect on newborn ICa was completely eliminated by Gpp(NH)p. The isoproterenol effect on adult ICa persisted after the washout of isoproterenol in the presence of Gpp(NH)p. Gpp(NH)p also reduced the stimulatory effect of 1 microM of forskolin by a factor of 2.0 and 8.2 for adult and newborn cells, respectively, in comparison to the control. Carbachol caused no additional effect on forskolin-stimulated ICa for either adult or newborn ICa in the presence of Gpp(NH)p. Pretreatment with pertussis toxin completely eliminated the inhibitory effect of carbachol on forskolin-stimulated ICa for both groups. In addition, the effect of forskolin on ICa was markedly enhanced by the pertussis toxin pretreatment in newborn cells, whereas the enhancement was relatively small for adult cells. We conclude that the muscarinic cholinergic influence on L-type ICa decreases after birth in rabbit ventricular cells, presumably through a diminishing influence of an inhibitory G protein on regulating adenylyl cyclase during the postnatal period.

Adenylate Cyclase Toxin↗

PubMed1993

Hypertonic sucrose treatment enhances second messenger accumulation in vasopressin-sensitive cells.

When we treated vasopressin-sensitive vascular smooth muscle cells (A10 cells) and kidney cells (LLC-PK1 cells) with hypertonic sucrose and vasopressin, we observed a decrease in the internalization of radiolabeled vasopressin into these cells and an increase in the amount of second messenger present in these cells following vasopressin stimulation. In A10 cells exposed to hypertonic sucrose, there was an increase in the amount of cellular inositol phosphates accumulated in response to vasopressin compared with cells not exposed to hypertonic sucrose. Similarly, in hypertonic sucrose-treated LLC-PK1 cells, vasopressin increased the amount of adenosine 3',5'-cyclic monophosphate (cAMP) present within the cells compared with LLC-PK1 cells not exposed to hypertonic sucrose. Hypertonic sucrose treatment inhibited receptor-mediated endocytosis in both these cell lines. Hypertonic sucrose alone did not increase the basal amounts of inositol phosphates or cAMP present in A10 or LLC-PK1 cells, respectively. Hypertonic sucrose treatment inhibits receptor endocytosis and increases second messenger concentrations in vasopressin-sensitive cells.

1-Methyl-3-isobutylxanthine↗

PubMed1993

Infanticide in England and Wales.

In England and Wales children under one year of age are at four times greater risk of becoming victims of homicide than either older children or the general population. The annual rate of infant homicide (45 per million) has remained relatively constant since the Homicide Act (1957) in contrast with a progressive fall in the infant mortality rate. Details from Home Office records of all infants under a year who were the victims of homicide during 1982-1988 are presented. Infants were most at risk on the first day of life--neonates accounted for 21% of victims and 13% of the victims were between one day and one month old. Thereafter the proportion decreased steadily so that by the final quarter of the first year the risk of becoming a homicide victim equalled that of the general population. Excluding neonates, there were more male victims than female ones, especially in the first three months. A parent was the most likely perpetrator. For all neonaticides the mother was recorded as a suspect, 36% of these mothers were subsequently indicted, all but two were convicted of infanticide and all their convictions resulted in probation. For children over a day marginally more fathers than mothers were recorded as the prime suspect. Mother and father suspects were equally likely to be indicted and also equally likely to be convicted of a homicide offence. However, mothers received both less severe convictions and less severe sentences than fathers. Fathers were more likely than mothers to have killed their infants using violence which wounded. Nonetheless sentences were unrelated to the brutality of the offence: mothers who had killed with wounding violence received less severe penalties than fathers who had killed in a non-wounding way.

England↗

PubMed1993

Postnatal psychiatric illness: the impact on partners.

Out of 24 spouses of women with postnatal psychiatric illness admitted to a mother and baby unit over 12 months, 12 were found to be psychiatrically ill, as defined by RDC or DSM-III criteria. The rate of psychiatric disorder was higher in these men than in a control group of men whose partners remained well after childbirth and a group of men whose partners were admitted to a psychiatric hospital with non-puerperal illness. The onset of psychiatric illness in the men typically followed admission of their wives to the mother and baby unit. Other associations with illness in the man were a history of chronic social problems, previous psychiatric episodes, and a poor relationship with his own father.

Adult↗

PubMed1993

Enteroaggregative Escherichia coli may be a new pathogen causing acute and persistent diarrhea.

The role of Hep-2 cell adherent Escherichia coli (EAEC) of localized (EAEC-L), diffuse (EAEC-D) and aggregative (EAggEC) phenotype, was investigated in 254 children aged < or = 48 months seeking treatment for non-bloody diarrhea at an outpatient clinic, and in 107 age-matched controls. The stool excretion rates of single isolates from patients/controls for the different phenotypes of Hep-2 cell adherent E. coli were: EAEC-L, 5.9/2.8%, p = 0.33; EAEC-D, 7.5/12.1%, p = 0.22; and EAggEC, 11.8/3.7%, p = 0.03. When patients were categorized by pre-admission diarrheal duration > or = 14/< 14 days, the excretion rates were EAEC-L, 0/7.1%; EAEC-D, 9.5/7.1%, and EAggEC, 21.4/9.9%, the difference approaching significance only for EAggEC (p = 0.06). These findings suggest that EAggEC may be an important cause of diarrhea in children, with a predilection to cause prolonged disease.

Acute Disease↗