Search PubMed⌕ Search

Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 541 records · Page 30Linked to original sources
PubMed1998

Metal mediated sterol receptor-DNA complex association and dissociation determined by electrospray ionization mass spectrometry.

The vitamin D receptor (VDR) binds to specific DNA sequences termed vitamin D response elements (VDREs) thereby enhancing or repressing transcription. We have used electrospray ionization mass spectrometry to examine the interaction between the DNA-binding domain of the vitamin D receptor (VDR DBD) with a double-stranded DNA (dsDNA) sequence containing the VDRE from the mouse osteopontin gene. The VDR DBD was shown to bind to the appropriate DNA sequence only when bound to 2 moles of zinc (Zn2+) or cadmium (Cd2+) per mole of protein. Additional binding of Zn2+ or Cd2+ by the protein caused the protein to dissociate from the dsDNA. These results show that the VDR DBD/DNA metal-dependent association occurs when the receptor is occupied by 2 moles of Zn2+ per mole of protein and that further binding of Zn2+ to the protein causes dissociation of the complex.

Animals↗
PubMed1998

Plasmodium vivax causing pancytopenia after allogeneic blood stem cell transplantation in CML.

A 20-year-old male patient with chronic myeloid leukemia (CML), in chronic phase, underwent allogeneic blood stem cell transplantation in August 1996. Engraftment was well documented in the marrow on day 19, but pancytopenia and mild splenomegaly continued. On day +70, the patient developed severe anemia and had one pyrexial episode. He was detected to have malaria (Plasmodiium vivax). After chloroquin therapy, the pancytopenia reversed completely. We suggest that malaria should be considered as a possible cause of pancytopenia in the post-transplant period in endemic areas.

Adult↗
PubMed1998

Protein kinase C isoform levels in normal and sodium dodecyl sulphate-irritated mouse skin.

Protein kinase C (PKC) comprises a family of related phospholipid-dependent serine/threonine protein kinases. PKC is important in signal transduction, regulating cell proliferation and differentiation. Recently, it has also been suggested that PKC may play a part in the pathogenesis of contact dermatitis. However, the expression of PKC isoforms in the skin of mice with irritant contact dermatitis (ICD) has not been examined. In this study, ICD was induced in mouse skin by applying 5%, 10% and 20% sodium dodecyl sulphate (SDS) in Finn chambers on the backs of mice and fixing with surgical dressings for 24 h. Depending upon the SDS concentration, mild to strong skin irritant reactions were observed 24 h after removal of the irritant patches. The intensity of the reactions increased with the increasing concentration of SDS. PKC isoforms alpha, beta, gamma and delta were all detected in normal mouse skin by Western immunoblotting. The specificity of the PKC isoforms detected was identified further by competitive Western immunoblotting. Compared with normal mouse skin treated with double-distilled water, the levels of PKC isoforms alpha, beta, gamma and delta in the SDS-irritated mouse skin was decreased by 24.8-75.8%. These results suggest that, in SDS-ICD, mouse skin PKC isoforms alpha, beta, gamma and delta are down-regulated. The significance of this decrease is under further investigation.

Animals↗
PubMed1998

Pharmacokinetics, bioavailability and dosage regimen of sulphadiazine (SDZ) in camels (Camelus dromedarius).

The pharmacokinetics of sulphadiazine (SDZ) (100 mg/kg, body weight) were investigated in six camels (Camelus dromedarius) after intravenous (i.v.) and oral (p.o.) administration. Following i.v. administration, the overall elimination rate constant (beta) was 0.029 +/- 0.001/h and the half-life (t1/2beta) was 23.14 +/- 1.06 h. The apparent volume of distribution (Vd(area)) was 0.790 +/- 0.075 L/kg and the total body clearance (ClB) was 23.29 +/- 2.50 mL/h/kg. After p.o. administration, SDZ reached a peak plasma concentration (Cmax(cal.)) of 62.93 +/- 2.79 microg/mL at a post injection time of (Tmax(cal.)) 22.98 +/- 0.83 h. The elimination half-life was 19.79 +/- 1.22 h, not significantly different from that obtained by the i.v. route. The mean absorption rate constant (Ka) was 0.056 +/- 0.002 h(-1) and the mean absorption half-life (t1/2Ka) was 12.33 +/- 0.37 h. The mean availability (F) of sulphadiazine was 88.2 +/- 6.2%. To achieve and maintain therapeutically satisfactory plasma SDZ levels of > or = 50 microg/mL, the priming and maintenance doses would be 80 mg/kg and 40 mg/kg intravenously and 90 mg/kg and 45 mg/kg orally, respectively, to be repeated at 24 h intervals.

Animals↗
PubMed1998

Tracheal intubation without neuromuscular blockade in children: a comparison of propofol combined either with alfentanil or remifentanil.

Forty healthy children, aged between two and 12 years of age undergoing elective surgery where the anaesthetic technique involved tracheal intubation followed by spontaneous ventilation were studied. Induction of anaesthesia was with either alfentanil 15 micrograms.kg-1 or remifentanil 1 microgram.kg-1 followed by propofol 4 mg.kg-1 to which lignocaine 0.2 mg.kg-1 had been added. Intubating conditions were graded on a four point scale for ease of laryngoscopy, vocal cord position, degree of coughing, jaw relaxation and limb movement. All children were successfully intubated at the first attempt. There were no significant differences in the assessments of intubating conditions between the two groups. Arterial blood pressure and heart changes were similar in the two groups with both alfentanil and remifentanil attenuating the haemodynamic response to tracheal intubation. The time taken to resumption of spontaneous ventilation was similar in both groups.

Alfentanil↗
PubMed1998

Paroxetine: a review of clinical experience.

The selective serotonin reuptake inhibitor paroxetine has been extensively studied and is now an established therapy for the treatment of depressive disorders. Paroxetine has demonstrated efficacy in major depression in both young and elderly patients, with an improved tolerability profile over conventional antidepressants. Paroxetine is effective across a continuum of anxiety and depressive disorders, including severe depression, depression with anxiety, comorbid depression and obsessive-compulsive disorder. The first agent of its class licensed for use in panic disorder, paroxetine has been shown to be effective in reducing the number of panic attacks and preventing relapse. A worldwide clinical database has established that paroxetine has a benign adverse event profile. Paroxetine therefore offers an effective and well tolerated treatment for a broad spectrum of psychiatric disorders.

Antidepressive Agents, Second-Generation↗
PubMed1998

Follow-up study of blindness attributed to cataract in Karnataka State, India.

AIM: Presentation of the results of rapid assessments of bilateral cataract blindness in persons 50 years of age and older in 19 districts of Karnataka State, India. MATERIALS: A total of 21,950 persons 50 years of age and older in 19 out of 20 districts were examined. In each district, 15 clusters were randomly selected and in each cluster the visual acuity and lens status were assessed in 90 persons 50 years of age and older. METHODS: Systematic Random Cluster Sampling was used. Assuming a prevalence of at least 4.3% and a design effect of 1.5, the survey was designed to give an estimated prevalence with a sampling error of 20% or less at 80% confidence. Visual acuity was measured with a tumbling E chart at 6 meters distance with available correction. Lens status was assessed by distant direct ophthalmoscopy with undilated pupil under semi-dark conditions. RESULTS: The average age and sex adjusted prevalence of cataract blindness was 4.93%, with a variation of 1.58% to 7.24% in different districts. The prevalence in females was higher than in males. Cataract Surgical Coverage, an indicator for coverage and service utilization, varied from 42% to 68% in different districts. On average, males had a higher coverage than females. Of all aphakic eyes in the sample, 26.4% could not see 6/60. Barriers to cataract surgery are linked to service providers. CONCLUSIONS: Rapid assessments for cataract blindness in persons aged 50 years and older can be conducted at district level in India with existing resources and at affordable costs. The results suggest an increase in cataract blindness since the previous survey of 1986. The long-term visual outcome needs improvement. Change in barriers to cataract surgery requires a shift in health education strategy and messages. The large variation in prevalence justifies district-level surveys. A change in the sampling frame from 15 clusters of 90 to 28 x 40 or 37 x 30 will increase the precision.

Blindness↗
PubMed1998

Atypical response to chemotherapy in neurotuberculosis.

Five cases of intracranial tuberculosis with atypical response to antitubercular chemotherapy are reported. In these cases tuberculomas either increased in sizes or first developed during course of adequate chemotherapy for tubercular meningitis or postmeningitic hydrocephalus. In two of these cases granulomas were located deeply in the parenchyma; however, these were on the surface in the other three. Atypical response to antitubercular treatment was observed at 5 weeks, 8 weeks, 2 months (in two cases) and 6 months. Glucocorticoid therapy was instituted in two cases and surgical excision of tuberculomas performed in the others. Recovery was good in all the five cases excluding visual loss, which remained unchanged in two cases because of prexisting secondary optic atrophy.

Adolescent↗
PubMed1998

Spontaneous CSF rhinorrhoea due to temporosphenoidal encephalocele.

A 54-year-old woman was referred with spontaneous cerebrospinal fluid (CSF) rhinorrhoea. CT cisternography revealed a defect in the lateral wall of the left sphenoid sinus, with an anteromedial temperosphenoidal encephalocele associated with contrast leakage into the sinus. Subsequent monitoring showed raised intracranial pressure. Transcranial intradural repair of the encephalocele followed by lumboperitoneal shunt for the high pressure abolished the leakage of cerebrospinal fluid.

Acrylic Resins↗
PubMed1998

Pacemaker synchronization of electrically coupled rabbit sinoatrial node cells.

The effects of intercellular coupling conductance on the activity of two electrically coupled isolated rabbit sinoatrial nodal cells were investigated. A computer-controlled version of the "coupling clamp" technique was used in which isolated sinoatrial nodal cells, not physically in contact with each other, were electrically coupled at various values of ohmic coupling conductance, mimicking the effects of mutual interaction by electrical coupling through gap junctional channels. We demonstrate the existence of four types of electrical behavior of coupled spontaneously active cells. As the coupling conductance is progressively increased, the cells exhibit: (a) independent pacemaking at low coupling conductances, (b) complex dynamics of activity with mutual interactions, (c) entrainment of action potential frequency at a 1:1 ratio with different action potential waveforms, and (d) entrainment of action potentials at the same frequency of activation and virtually identical action potential waveforms. The critical value of coupling conductance required for 1:1 frequency entrainment was <0.5 nS in each of the five cell pairs studied. The common interbeat interval at a relatively high coupling conductance (10 nS), which is sufficient to produce entrainment of frequency and also identical action potential waveforms, is determined most by the intrinsically faster pacemaker cell and it can be predicted from the diastolic depolarization times of both cells. Evidence is provided that, at low coupling conductances, mutual pacemaker synchronization results mainly from the phase-resetting effects of the action potential of one cell on the depolarization phase of the other. At high coupling conductances, the tonic, diastolic interactions become more important.

Action Potentials↗
PubMed1998

Sevoflurane compared with halothane for tracheal intubation in children.

We have studied 40 healthy children, aged 3-10 yr, undergoing adenotonsillectomy, in a double-blind, randomized study. Intubating conditions were assessed when the pupils had become small and central after inhalation induction with either 5% halothane and 60% nitrous oxide in oxygen or 8% sevoflurane and 60% nitrous oxide in oxygen. The quality of tracheal intubation was graded according to ease of laryngoscopy, position of the vocal cords, coughing, jaw relaxation and movement of limbs. Fewer children had significant vocal cord movement on laryngoscopy (P < 0.01) and more had ideal intubating conditions when halothane was used (12 of 20 compared with seven of 20; ns). Time to reach the clinical end-point for intubation was reached sooner with halothane (P = 0.015). In all children the trachea was intubated successfully at the first attempt and all remained haemodynamically stable throughout induction.

Adenoidectomy↗
PubMed1998

Inhibition of the protein kinase C pathway promotes anti-CD95-induced apoptosis in Jurkat T cells.

The role of the basal activity of the serine/threonine protein kinase, protein kinase C (PKC) in the regulation of anti-CD95-induced apoptosis in Jurkat T cells was investigated. The PKC-specific inhibitor GF 109203X and the proposed cPKC-specific inhibitor Go 6976, in a concentration-dependent manner, increased the percentage of cells undergoing apoptosis induced by anti-CD95 mAb as demonstrated by propidium iodide (PI) staining, TUNEL assay and DNA fragmentation by gel electrophoresis. Furthermore, Go 6976 and GF 109203X abrogated phorbol myristate acetate-induced inhibition of anti-CD95-induced apoptosis. To examine the molecular mechanism by which PKC modulates anti-CD95-induced apoptosis, the effects of Go 6976 on known effector and regulatory molecules of cell death were studied. Increased recruitment of cells undergoing apoptosis was associated with enhanced anti-CD95-induced proteolytic cleavage of the most receptor-proximal cysteine protease caspase-8, subsequent cleavage and activation of the machinery protease caspase-3, and cleavage of the caspase substrates DNA-dependent protein kinase catalytic subunit, poly-(ADP-ribose) polymerase and lamin B1. CD95 and FADD protein levels in Jurkat T cells were not altered by Go 6976 treatment. In addition, Go 6976 did not alter protein levels and subcellular distribution of the anti-apoptotic molecules Bcl-2 and Bcl-xL. These data suggest indirectly that basal PKC activity acts at an early stage in the anti-CD95-induced caspase pathway to attenuate subsequent activation of downstream effector molecules and associated apoptosis in Jurkat T cells.

Antibodies, Monoclonal↗
PubMed1998

Correct assembly of human normal adult hemoglobin when expressed in transgenic swine: chemical, conformational and functional equivalence with the human-derived protein.

Structural and functional investigations of recombinant human hemoglobin A (HbA) isolated from the erythrocytes of transgenic swine coexpressing human alpha- and beta-globins have been carried out to authenticate its correct expression, post-translational processing and assembly. The HbA expressed in transgenic swine (TgHbA) is indistinguishable from the human-derived HbA in terms of its isoelectric pH, mass and elution pattern on a Mono S column. The chemical identity of the alpha- and beta-globin chains of TgHbA with the corresponding chains from human-derived HbA has been established by tryptic peptide mapping and amino acid sequencing. The proton NMR spectra of TgHbA have demonstrated that the conformational aspects of the protein around the heme pocket are indistinguishable from those of the control sample of HbA. The equivalence of the hydrogen bond pattern of TgHbA (in particular the inter-subunit surfaces) with that of authentic HbA has also been established by NMR studies. Consistent with these structural and conformational analyses, the TgHbA also exhibits complete functional equivalence with the human-derived HbA with respect to oxygen affinity, cooperativity, Bohr effect and allostery. Hence the studies presented here demonstrate that the transgenic swine system correctly transcribes the alpha- and beta-globin transgenes, translates the respective alpha- and beta-globin mRNA to generate the corresponding globin chains, carries out the correct cotranslational processing of the translated globin chains, inserts the heme into the globin chains in the same orientation as in the human-derived HbA and assembles the alpha- and beta-subunits into a functionally cooperative tetramer that exhibits a response to allosteric effectors identical with that of human-derived HbA. Thus, in the transgenic swine system, in vitro chemical manipulation steps such as those needed in the Escherichia coli and the yeast systems, to convert the rHbA expressed in these systems into forms functionally identical with that of the human-derived protein, are not needed. An additional advantage of the transgenic swine system is the stability of the transgenes over many generations. Hence the transgenic swine could serve as an excellent system for the production of human HbA (or its variants) for structure-function studies and for therapeutic applications.

Adult↗
PubMed1998

Induction of nitric oxide production and tumoricidal properties in murine macrophages by a new synthetic lipopeptide JBT3002 encapsulated in liposomes.

We studied activation to the tumoricidal state of murine peritoneal macrophages by liposomes containing a new synthetic analogue, JBT3002, of a lipoprotein from the outer wall of a gram-negative bacterium. The liposomes containing JBT3002 or CGP31362 were superior to liposomes containing muramyl tripeptide phosphatidylethanolamine (MTP-PE) for tumoricidal activation in three ways. First, efficient macrophage activation required lower concentrations of JBT3002 or CGP31362 than MTP-PE. Second, macrophage activation by JBT3002 was less dependent on priming by interferon-gamma. Third, MLV-JBT3002 activated tumoricidal properties in both lipopolysaccharide (LPS)-responsive and LPS-nonresponsive macrophages. The activation of tumoricidal properties by MLV-JBP3002 depended on protein tyrosine kinase (PTK) activity associated with phosphorylation of tyrosine. The major mechanism for tumoricidal activity in macrophages incubated with MLV-JBT3002 was due to increased activity of inducible nitric oxide synthase (iNOS) and, hence, production of nitric oxide (NO). We base this conclusion on the results of several experiments. First, MLV-JBT3002 was not directly toxic to tumor target cells. Second, the specific iNOS inhibitor NG-monomethyl-L-arginine abrogated tumor cell lysis by MLV-JBT3002-treated macrophages. Third, macrophages from iNOS knockout mice did not lyse tumor cells, even after incubation with high concentrations of MLV-JBT3002. These data suggest that liposomes containing the synthetic bacterial lipopeptide JBT3002 are potent activators of macrophage tumoricidal properties.

Acetylmuramyl-Alanyl-Isoglutamine↗