Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 469 records · Page 26Linked to original sources

PubMed1999

Identification of copper-zinc superoxide dismutase gene from enteroaggregative Escherichia coli.

We describe here the identification of sodC gene from enteroaggregative Escherichia coli (EAggEC). A 294 bp gene-specific fragment was amplified from the organism by DNA as well as RT-PCR using primers from bacterial sodC sequences. The metal co-factor present in the protein was confirmed by running samples in native gels and inhibiting with 2 mM potassium cyanide. However, the nonpathogenic E. coli possesses the gene but does not express it. Thus, the presence of copper-zinc superoxide dismutase encoded by sodC was demonstrated for the first time in EAggEC, which means it could be a novel candidate for a virulence marker.

Copper↗

PubMed1999

Detection of methylation damage in DNA of gastric cancer tissues using 32P postlabelling assay.

Gastric cancer is the most common cancer in Korea. The causes are still unknown but it has been speculated that gastric cancer is associated with consumption of foods rich in nitrates/nitrites or a high dietary intake of salt or pickled food. In the present study, we studied the level of alkylated DNA adducts formed in gastric cancer tissues in comparison with that in normal gastric mucosa. DNA was extracted from surgically removed gastric cancer tissues and patient-matched normal gastric mucosa. The level of N7-methyldeoxyguanosine was measured by 32P-postlabelling assay after high performance liquid chromatography (HPLC) enrichment. We found that the level of N7-methyldeoxyguanosine of gastric cancerous tissues was significantly higher than that of normal gastric mucosa (P=0.01685).

Adenocarcinoma↗

PubMed1999

Mutational analysis of glycosylation, membrane translocation, and cell surface expression of the hepatitis E virus ORF2 protein.

Hepatitis E virus (HEV) is the etiological agent for viral hepatitis type E, which is a major problem in the developing world. Because HEV cannot be cultured in vitro, very little information exists on the mechanisms of HEV gene expression and genome replication. HEV is a positive-strand RNA virus with three potential open reading frames (ORFs), one of which (ORF2) is postulated to encode the major viral capsid protein (pORF2). We earlier showed (S. Jameel, M. Zafrullah, M. H. Ozdener, and S. K. Panda, J. Virol. 70:207-216, 1996) pORF2 to be a approximately 88-kDa glycoprotein, carrying N-linked glycans and a potential endoplasmic reticulum (ER)-directing signal at its N terminus. Treatment with the drugs brefeldin A and monensin suggest that the protein may accumulate within the ER. Based on mutational analysis, we demonstrate Asn-310 to be the major site of N-glycan addition. In COS-1 cell expression and in vitro translation experiments, we confirm the ER-translocating nature of the pORF2 N-terminal hydrophobic sequence and show that the protein is cotranslationally, but not posttranslationally, translocated across the ER membrane. Earlier, we had also demonstrated cell surface localization of a fraction of the COS-1 cell-expressed pORF2. Using glycosylation- and translocation-defective mutants of pORF2, we now show that while transit of pORF2 into the ER is necessary for its cell surface expression, glycosylation of the protein is not required for such localization. These results may offer clues to the mechanisms of gene expression and capsid assembly in HEV.

Amino Acid Sequence↗

PubMed1999

A diagnostic rule for tuberculous meningitis.

Diagnostic confusion often exists between tuberculous meningitis and other meningoencephalitides. Newer diagnostic tests are unlikely to be available in many countries for some time. This study examines which clinical features and simple laboratory tests can differentiate tuberculous meningitis from other infections. Two hundred and thirty two children (110 tuberculous meningitis, 94 non-tuberculous meningitis, 28 indeterminate) with suspected meningitis and cerebrospinal fluid (CSF) pleocytosis were enrolled. Tuberculous meningitis was defined as positive CSF mycobacterial culture or acid fast bacilli stain, or basal enhancement or tuberculoma on computed tomography (CT) scan with clinical response to antituberculous treatment. Non-tuberculous meningitis was defined as positive CSF bacterial culture or Gram stain, or clinical response without antituberculous treatment. Thirty clinical/laboratory features of patients with tuberculous meningitis and non-tuberculous meningitis were compared by univariate and multiple logistic regression analysis. Five features were independently predictive of the diagnosis of tuberculous meningitis (p < 0.007): prodromal stage >/= 7 days, optic atrophy on fundal examination, focal deficit, abnormal movements, and CSF leucocytes < 50% polymorphs. When validated on another set of 128 patients, if at least one feature was present, sensitivity was 98.4% and, if three or more were present, specificity was 98.3%. This simple rule would be useful to physicians working in regions where tuberculosis is prevalent.

Child↗

PubMed1999

Thyroid hormones modulate zinc transport activity of rat intestinal and renal brush-border membrane.

Thyroid hormone status influences the Zn2+ and metallothionein levels in intestine, liver, and kidney. To evaluate the impact of thyroid hormones on Zn2+ metabolism, Zn2+ uptake studies were carried out in intestinal and renal brush-border membrane vesicles (BBMV). Steady-state Zn2+ transport in intestinal and renal cortical BBMV was increased in hyperthyroid (Hyper-T) rats and decreased in the hypothyroid (Hypo-T) rats relative to euthyroid (Eu-T) rats. In both the intestinal and renal BBMV, Hyper-T rats showed a significant increase in maximal velocity compared with Eu-T and Hypo-T rats. Apparent Michaelis constant was unaltered in intestinal and renal BBMV prepared from the three groups. Fluorescence anisotropy of diphenyl hexatriene was decreased significantly in intestinal and renal brush-border membrane (BBM) isolated from Hyper-T rats compared with Hypo-T and Eu-T rats. A significant reduction in the microviscosity and transition temperature for Zn2+ uptake in intestinal and renal BBM from Hyper-T rats is in accordance with the increased fluidity of these BBMs. These findings suggest that the increased rate of Zn2+ transport in response to thyroid hormone status could be associated with either an increase in the number of Zn2+ transporters or an increase in the active transporters due to alteration in the membrane fluidity. Thus the thyroid hormone-mediated change in membrane fluidity might play an important role in modulating Zn2+ transport activity of intestinal and renal BBM.

Animals↗

PubMed1999

Expression of 25(OH)D3 24-hydroxylase in distal nephron: coordinate regulation by 1,25(OH)2D3 and cAMP or PTH.

Previous studies using microdissected nephron segments reported that the exclusive site of renal 25-hydroxyvitamin D3-24-hydroxylase (24OHase) activity is the renal proximal convoluted tubule (PCT). We now report the presence of 24OHase mRNA, protein, and activity in cells that are devoid of markers of proximal tubules but express characteristics highly specific for the distal tubule. 24OHase mRNA was undetectable in vehicle-treated mouse distal convoluted tubule (DCT) cells but was markedly induced when DCT cells were treated with 1,25 dihydroxyvitamin D3 [1,25(OH)2D3]. 24OHase protein and activity were also identified in DCT cells by Western blot analysis and HPLC, respectively. 8-Bromo-cAMP (1 mM) or parathyroid hormone [PTH-(1-34); 10 nM] was found to potentiate the effect of 1, 25(OH)2D3 on 24OHase mRNA. The stimulatory effect of cAMP or PTH on 24OHase expression in DCT cells suggests differential regulation of 24OHase expression in the PCT and DCT. In the presence of cAMP and 1, 25(OH)2D3, a four- to sixfold induction in vitamin D receptor (VDR) mRNA was observed. VDR protein, as determined by Western blot analysis, was also enhanced in the presence of cAMP. Transient transfection analysis in DCT cells with rat 24OHase promoter deletion constructs demonstrated that cAMP enhanced 1, 25(OH)2D3-induced 24OHase transcription but this enhancement was not mediated by cAMP response elements (CREs) in the 24OHase promoter. We conclude that 1) although the PCT is the major site of localization of 24OHase, 24OHase mRNA and activity can also be localized in the distal nephron; 2) both PTH and cAMP modulate the induction of 24OHase expression by 1,25(OH)2D3 in DCT cells in a manner different from that reported in the PCT; and 3) in DCT cells, upregulation of VDR levels by cAMP, and not an effect on CREs in the 24OHase promoter, is one mechanism involved in the cAMP-mediated modulation of 24OHase transcription.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1999

Electrical interactions among real cardiac cells and cell models in a linear strand.

Previous work with model systems for action potential conduction have been restricted to conduction between two real cells or conduction between a model cell and a real cell. The inclusion of additional elements to make a linear strand has allowed us to investigate the interactions between cells at a higher level of complexity. When, in the simplest case of a linear strand of three elements, the conductance between elements 2 and 3 (GC2) is varied, this affects the success or failure of propagation between elements 1 and 2 (coupled by GC1) as well as the success or failure of propagation between elements 2 and 3. Several major features were illustrated. 1) When GC1 was only slightly greater than the coupling conductance required for successful propagation between a model cell and a real cell, addition of a third element of the strand either prevented conduction from element 1 to element 2 (when GC2 was high) or allowed conduction from element 1 to element 2 but not conduction from element 2 to element 3 (when GC2 was low). 2) For higher levels of GC1, there was an allowable "window" of values of GC2 for successful conduction from element 1 through to element 3. The size of this allowable window of GC2 values increased with increasing values of GC1, and this increase was produced by increases in the upper bound of GC2 values. 3) When the size of the central element of the strand was reduced, this facilitated conduction through the strand, increasing the range of the allowable window of GC2 values. The overall success or failure of conduction through a structure of cells that has a spatially inhomogeneous distribution of coupling conductances cannot be predicted simply by the average or the minimum value of coupling conductance but may depend on the actual spatial distribution of these conductances.

Animals↗

PubMed1999

Thalamic glioblastoma with cerebrospinal fluid dissemination in the peritoneal cavity.

Glioblastoma multiforme is one of the commonest primary malignant tumours of the brain with rare incidence of extracranial metastases. Systemic dissemination via the CSF or CSF diversionary shunt procedures is also rare. The reported 9-year-old child was a case of thalamic glioblastoma with hydrocephalus who underwent biventriculoperitoneal shunting before tumour decompression and radiotherapy. The child developed incapacitating ascites 8 months following surgical decompression and 9 months after the shunt diversion which was found to be caused by CSF dissemination of the glioblastoma via the ventriculoperitoneal shunt. The child ultimately succumbed to his disease.

Ascites↗

PubMed1999

Psychotropic drugs in mothers' milk: a comprehensive review of assay methods, pharmacokinetics and of safety of breast-feeding.

Many mentally ill women want to breast-feed their babies but, if they are taking psychotropic drugs, there is very little systematic data upon which to base decisions about whether or not it is safe to do so. We therefore attempt to provide a comprehensive and critical summary of existing case reports and of studies of breast-feeding in relation to commonly used psychotropic drugs. The literature review focuses on the following drugs: antidepressants: tricyclics and serotonin selective reuptake inhibitors (SSRIs); antipsychotic drugs: chlorpromazine, perphenazine, haloperidol and clozapine; mood stabilizers: lithium and carbamazepine; and benzodiazepines. The research literature consists mainly of single case reports and there have been very few attempts at controlled, longitudinal investigations. Findings are often difficult to compare because of differences in methods or because of lack of key information. Most data are available about the tricyclic antidepressants but even here we have found that the reports cover only a grand total of 66 mother-infant pairs. Dilemmas about whether or not to contraindicate breast-feeding arise most commonly in relation to postnatal depression. The findings to date suggest that provided that infants are healthy at the outset it is likely that the benefits of breast-feeding will outweigh potential hazards if their mothers are taking established tricyclic drugs at recommended dose levels. Much less is known about risks associated with SSRI antidepressants or about antipsychotic drugs such as phenothiazines and butyrophenones or mood stabilizers such as carbamazepine, all of which enter breast-milk. Safeguards are suggested for future single case studies, which, as they accumulate, will provide a platform for mounting controlled prospective studies properly to test for any acute toxic effects and for possible long-term adverse effects of such drugs on infants' development. Appendix 1 is a review of assay methods. Appendix 2 examines pharmacokinetic factors in newborn preterm and sick infants with special reference to contraindications to breast-feeding. Appendix 3 is a review of methods for assessing infant health and development.

Adult↗

PubMed1999

Sensorimotor and cognitive development of infants of mothers with schizophrenia.

BACKGROUND: The parenting environment provided by mothers with schizophrenia is likely to contribute to the cognitive impairment observed in their offspring. AIMS: To assess the relative contribution of maternal schizophrenia, obstetric factors and mothers' lifestyle to the cognitive development of infants in their first year. METHOD: The Bayley Scales of Infant Development were administered to 19 infants of mothers with schizophrenia, 34 with non-psychotic depression in the mother, 29 with affective psychosis in the mother and 24 normal controls when the babies were two and seven months of age. RESULTS: At two months, infants of mothers with schizophrenia and of those with affective psychosis had lower mental development index (MDI) scores than controls. At seven months, infants of mothers with schizophrenia had lower MDI scores than all other groups. When infant birth weight and mothers' social class were taken into account there was no effect of maternal schizophrenia on infants' MDI scores. CONCLUSIONS: Infants of mothers with schizophrenia are likely to have impaired cognitive development. This may be due in part to environmental factors such as the mother's lifestyle.

Adult↗

PubMed1999

1,2-Diarylimidazoles as inhibitors of cyclooxygenase-2: a quantitative structure-activity relationship study.

The cyclooxygenase-2 (COX-2) enzyme inhibition activity of derivatives of 1,2-diarylimidazole is analysed through Fujita-Ban and Hansch approaches. The analyses have helped to ascertain the role of different substituents in explaining the observed inhibitory potency of these analogues. From both approaches it is revealed that the more hydrophobic X-substitutions that are present at the 3- and 4-positions of the aryl ring and are also non-hydrogen acceptor in character improve inhibitory action of a compound. The smaller substituent either H or F is preferred at the 2-X position as it is involved in steric interaction. Likewise, the substituent-NH2 instead of Me at R is advantageous. Further, for a data set of 35 congeners, the selectivity ratio related to the constitutive COX-1 isozyme is also analysed through the Fujita-Ban approach. The derived contributions of parent moiety and various substituents have helped to predict the substitution pattern in the design of more effective compounds that were not in the original data set.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1999

Palliative subtotal vertebrectomy with anterior and posterior reconstruction via a single posterior approach.

OBJECT: Laminectomy for the treatment of spinal metastatic disease is ineffective. Total spondylectomy requiring both anterior and posterior operations may cause undue morbidity in patients with a limited life expectancy. The authors demonstrate the technique, feasibility, and success of subtotal vertebrectomy that is followed by anterior and posterior reconstruction via a simple posterior approach. Although this remains a palliative procedure, it provides circumferential decompression and spinal stabilization by using rigid hardware. METHODS: The authors present a review of nine of 43 consecutive patients with spinal metastatic disease who underwent operation in a 42-month period. Via a single midline posterior approach, the authors performed single-stage circumferential decompression of the theca followed by anterior and posterior reconstruction. Anterior support is provided by a methylmethacrylate reconstruction retained with Steinmann pins. Posterior reconstruction is achieved by placement of rigid hook or pedicle screw and rod instrumentation. Eight of the nine patients died of progression of underlying disease. All patients remained pain free until days before they died. Except for a patient with paraplegia who did not recover, all other patients remained ambulatory. Despite radio-, chemo-, and steroid therapy, there were no wound infections or breakdowns. One patient underwent reoperation because of a technical error. CONCLUSIONS: Use of the near-total vertebrectomy followed by anterior and posterior reconstruction from T2 to L3 by using a single midline posterior approach spares the patient, who has a limited life expectancy, the operative risks associated with thoracotomy or thoracoabdominal approaches. The authors restrict the procedure for use in patients with extensive bony disease, noncontiguous spinal involvement, visceral metastases, other contraindications to a transcavitary procedure, and those with advanced age.

Adenocarcinoma↗

PubMed1999

Surgical management of right atrial myxomas. A 15 year experience with review of the literature.

BACKGROUND: A retrospective study to evaluate the clinical symptoms, signs, investigations, surgical technique and follow-up of an uncommon cardiac tumour. METHODS: Experimental design and setting: this retrospective study was carried out in a tertiary care hospital in South India on patients treated from 1981 to 1996. Duration of follow-up has been for a maximum period of 9.5 years. PARTICIPANTS: all patients who were diagnosed to have right atrial myxoma were included in this study. There were seven patients (4 males, 3 females) with ages ranging from 16 to 52 years. INTERVENTIONS: six of these patients underwent complete excision. One patient who presented with SVC obstruction had locally invasive tumour and only a biopsy was done. In order to reduce the risk of intraoperative pulmonary embolism in the last two cases, we crossclamped the pulmonary artery as soon as cardiopulmonary bypass was initiated. RESULTS: There was one postoperative death due to refractory right ventricular failure (14.3%). Four patients have been followed-up for a mean of 40.7 months. All of them are free of recurrence and most of them are asymptomatic. CONCLUSIONS: Right atrial myxoma is a rare usually benign cardiac tumor whose definitive diagnosis is made on the basis of 2D echocardiography. The crucial aspects of surgery are measures for prevention of intraoperative embolism, en-bloc excision of the tumour with a wide cuff of normal tissue and inspection of all four chambers in order to avoid missing tumour emboli or an occasional multicentric lesion. Patients with myxomatous emboli into the pulmonary artery require simultaneous pulmonary embolectomy.

Adolescent↗

PubMed1999

Choroid plexus papilloma of cerebellopontine angle with extension to foramen magnum.

A case of choroid plexus papilloma resembling meningioma of cerebellopontine (CP) angle with its extension to foramen magnum is presented. Occurrence of this tumour in CP angle is very rare. Its extension towards foramen magnum is further rare. It was a real diagnostic enigma preoperatively as the tumour was resembling meningioma upto some extent on radiological study. Retromastoid craniectomy with microsurgical excision of tumour and its extension was achieved in toto. Tumour was attached to few rootlets of lower cranial nerves which were preserved. Attachment of the tumour with lower cranial nerves again caused diagnostic confusion with neurofibroma intraoperatively.

Adult↗

PubMed1999

Kala-azar epidemic in Varanasi district, India.

Reports at the Sir Sunder Lal Hospital, Banaras Hindu University, of a large number of kala-azar cases from one particular village in Varanasi district, Uttar Pradesh, led us to carry out an epidemiological study of the situation using standard techniques. The overall prevalence and case fatality of the disease were 12.9% and 10.5%, respectively. A history of fever and hepatosplenomegaly was noted for all the cases. The case definition was the presence of parasites in bone marrow or splenic aspirate smears. The disease was more prevalent among adults, but occurred also among children. However, there was no clear linear relationship between the prevalence of the disease and age group. Kala-azar occurred among males and females, and its prevalence did not correlate significantly with income. Since the disease vector continues to be present in the study area, the health authorities should take strong steps to control the disease.

Adolescent↗

PubMed1999

Association of lower cranial nerve schwannoma with spinal ependymoma in ? NF2.

A 15 year old male, who had earlier been operated for intraspinal intramedullary ependymoma, subsequently developed a right cerebello pontine (CP) angle mass. A diagnosis of right CP angle ependymoma was considered, in view of established histology of previously operated spinal lesion. Histopathological examination of the well defined extra-axial mass, which was attached with ninth cranial nerve, however revealed a schwannoma. A diagnosis of Neurofibromatosis-2 (NF2) is strongly suspected, because of well established fact, that the spinal ependymomas may have association with lower cranial nerve schwannomas in NF2. Cranial and spinal MRI screening for early diagnosis of associated, asymptomatic lesions, in suspected cases of NF2, particularly in children, is recommended.

Adolescent↗

PubMed1999

Raising the "glass ceiling" for ethnic minority women in health care management.

Ethnic minority women are well represented in the work force and in the health care system in general, but do not have a similar level of representation in the management sector. This paper explores three strategies for schools of health administration to consider to lessen the effect of a "glass ceiling" that may be encountered by ethnic minority women aspiring to positions of leadership in health services agencies. These strategies are advancing affirmative action, valuing ethnic women in health administration education, and investigating diversity management. Inherent in each of the three strategies is the need for acknowledgment and more open discussion of the "glass ceiling." Problem-solving in relation to the potential for systemic discrimination adversely affecting ethnic minority women in senior health care management positions, and greater study of the three strategies using both qualitative and quantitative methodologies is also needed.

Career Mobility↗

PubMed1999

Analysis of expression of cGMP-dependent protein kinase in rabbit heart cells.

We previously showed that stimulation of cGMP-dependent protein kinase (PKG) stimulates L-type calcium current in newborn but not in adult rabbit ventricular myocytes. We have now isolated rabbit PKG type Ialpha cDNA (+1 to 2095), determined the sequence, and analyzed specific expression of PKG in adult and newborn rabbit heart by Western and Northern analyses to elucidate the developmental decline in the significance of PKG in cardiac function. We obtained full-length cDNA of PKG Ialpha from newborn rabbit heart mRNA with reverse transcription-polymerase chain reaction. The coding region of rabbit PKG Ialpha showed 94% homology to sequences of human and bovine PKG Ialpha. The deduced amino acid sequence of 671 amino acids showed seven substitutions between rabbit and either human or bovine PKG Ialpha. The major substitutions were found in the cGMP-binding domain. The cloned PKG 1alpha cDNA was expressed in COS cells. Expressed PKG showed cGMP stimulated PKG activity and immunoreactivity. Northern blot analysis of cardiac tissue demonstrated PKG Ialpha mRNA of 6.8 kb, with much higher levels in newborn than in adult cells. Western analysis in homogenates from ventricular tissues and isolated ventricular myocytes of rabbit heart showed much higher expression of PKG type I protein in newborn compared with adult cells. These findings suggest that PKG is developmentally regulated in rabbit heart and is expressed at a much higher level in newborn than in adult cells. The greater expression of PKG in newborn cells could be responsible for differences in the significance of cGMP in adult and newborn rabbit cells.

Amino Acid Sequence↗