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Biomedical subjects

P Kumar

Publications and source records attributed to P Kumar.

At least 487 records · Page 27Linked to original sources
PubMed1993

Antibody levels and response to pneumococcal vaccine in steroid-dependent asthma.

Immunization with pneumococcal vaccine is recommended for patients with chronic respiratory diseases, and is also used to evaluate antibody responses to polysaccharide antigens. We determined the effect of chronic prednisone treatment on immunoglobulin levels, pneumococcal antibody levels, and on the serologic response to pneumococcal vaccination. We studied 14 adult steroid-dependent asthmatics receiving daily or alternate day prednisone, 10 to 35 mg, and 14 age-matched, nonsteroid dependent asthmatic patients. Immunoglobulin levels were within the normal range in all patients. There was no difference in the pre-immunization antipneumococcal polysaccharide antibody levels against serotypes 3, 7F, 9N, and 14 between steroid-dependent and nonsteroid-dependent asthmatic patients. All patients had increases in antipneumococcal antibody levels 4 weeks after pneumococcal immunization. Mean post-immunization pneumococcal antibody titers were similar in steroid-dependent and nonsteroid-dependent asthmatic patients. All patients either had or developed levels > or = 300 ng Ab N/mL against one or more pneumococcal serotypes. We conclude that chronic prednisone treatment in steroid-dependent asthmatic adults does not significantly affect immunoglobulin levels, pneumococcal antibody levels, or specific antibody responses to pneumococcal immunization.

Adult↗
PubMed1993

Antibiotic therapy for bacterial meningitis in children in developing countries.

We carried out a study to investigate the effectiveness of chloramphenicol alone as a treatment for bacterial meningitis. A total of 70 consecutive children aged > 3 months with bacterial meningitis, who had been admitted to the paediatric hospital of the All India Institute of Medical Sciences, were randomized to receive chloramphenicol alone or chloramphenicol + penicillin. The two groups were matched with each other. Treatment failure occurred with three (9%) patients in the chloramphenicol-alone group and with four (12.1%) patients in the combination therapy group (P > 0.05). The mean duration of intravenous therapy, the number of intravenous cannulae used per patient, and the incidence of thrombophlebitis were significantly higher for the group that received the combination therapy. Also, the cost of using chloramphenicol + penicillin was four times higher than that of chloramphenicol alone. Hence, chloramphenicol alone was as effective as chloramphenicol + penicillin and much cheaper and more convenient to use.

Child↗
PubMed1992

Detection of new metabolites of trifluridine (F3TdR) using 19F NMR spectroscopy.

The metabolism of 5-trifluoromethyl-2'-deoxyuridine (trifluridine, F3TdR) in male BALB/C mice has been studied by 19F NMR spectroscopy. Contrary to previous reports, a number of fluorinated metabolites were observed in urine, whole livers and blood samples taken from mice after i.p. injection of F3TdR. The present study describes the identification of two new metabolites in mouse urine using the 19F NMR technique. The NMR of crude urine showed the presence of F3TdR 5-trifluorothymine (F3T), the newly-identified metabolites, 5-trifluoromethyl-5,6-dihydrouracil (DHF3T) and 5-trifluoromethyl-5,6-dihydroxyracil (DOHF3T), and several new, as yet unidentified fluorinate metabolites. These two new metabolites were characterized by comparison to authentic compounds prepared synthetically from F3T.

Animals↗
PubMed1992

ABA-induced 'lipid melting' and its reversal by umbelliferone in the plasmalemma of guard cell protoplasts: a breakthrough in plant hormone-receptor binding and hormone action.

The dynamics of stomatal opening and closure had to date been ascribed largely to the K(+)-fluxes and cell wall elasticity. Using protoplasts of guard cells of Vicia faba as model system, we document convincing first hand evidence a that lipid phase alterations could regulate ABA-induced closure of stomates and its reversal by umbelliferone. Backed up by the presence of plasmalemma-located ABA-receptor in guard cells, a novel theory could be put forth explaining guard cell opening and closure mediated by hormone induced reconfiguration via a probable lipid-protein lattice modification. The phase reversal of the plasmalemma by umbelliferone is postulated to be through modified hormone receptor complex structure, which is yet to be substantiated.

Abscisic Acid↗
PubMed1992

Apoptosis and DNA fragmentation precede TNF-induced cytolysis in U937 cells.

The hypothesis that activation of apoptosis and DNA fragmentation is involved in TNF-mediated cytolysis of U937 tumor cells was investigated. Morphological, biochemical, and kinetic criteria established that TNF activates apoptosis as opposed to necrosis. Within 2-3 h of exposure to TNF, U937 underwent the morphological alterations characteristic of apoptosis. This was accompanied by cleavage of DNA into multiples of nucleosome size fragments. Both of these events occurred 1-2 h prior to cell death as defined by trypan blue exclusion or 51Cr release. DNA fragmentation was not a non-specific result of cell death since U937 cells lysed under hypotonic conditions did not release DNA fragments. The percentage of cells undergoing apoptosis depended on the concentration of TNF and was augmented by the addition of cycloheximide. A TNF-resistant variant derived from U937 did not undergo apoptosis in response to TNF, even in the presence of cycloheximide. Furthermore, TNF could still activate NFkB in this variant, suggesting that this pathway is not involved in TNF-mediated cytotoxicity. Two agents known to inhibit TNF-mediated cytotoxicity, ZnSO4 and 3-aminobenzamide, were shown to inhibit TNF-induced apoptosis. Taken altogether, these data support the hypothesis that activation of apoptosis is at least one essential step in the TNF lytic pathway in the U937 model system.

Benzamides↗
PubMed1992

SCM4, a gene that suppresses mutant cdc4 function in budding yeast.

The gene SCM4 encodes a protein which suppresses a temperature-sensitive allele of the cell division cycle gene CDC4 in Saccharomyces cerevisiae. SCM4 was cloned on a 1.8 kb BamHI fragment of yeast genomic DNA in the high copy-number vector pJDB207, which results in a 50- to 100-fold increase in the level of the 700 nucleotide SCM4 transcript in vivo. The SCM4 gene encodes a 20.2 kDa protein of 187 amino-acids with a clear tripartite domain structure in which a region rich in charged residues separates two domains of largely uncharged amino acids. Although the apparent allele specificity of cdc4 suppression suggests that the CDC4 and SCM4 proteins interact, disruption of SCM4 demonstrates that the gene product is not essential for mitosis or meiosis; however, it may be a member of a family of related, functionally redundant proteins.

Alleles↗
PubMed1992

Clinical studies in workers engaged in maintenance of watermark moulds in a paper mill.

Thirty subjects engaged in maintenance and repair of moulds used for producing watermarks on paper were studied, along with 27 control subjects from the same paper mill. The workers were simultaneously exposed to copper, chromium, zinc, xylol, and fumes of sulphuric acid in the course of their work. The study subjects were investigated for clinical, occupational, radiological haematological and psychological details. The aforementioned combined exposure was found to be responsible for a high prevalence of symptoms pertaining to the respiratory system and higher nervous functions. Breathlessness (26.7%), expectoration (10.0%) and emphysema (10.0%) were significantly higher among the exposed subjects. The exposed subjects also showed lowered visuomotor coordination and delayed reaction to light and sound stimuli.

Adult↗
PubMed1992

The value of intraoperative scans during CT-guided stereotactic procedures.

The accuracy stereotactic procedures performed during the pre-computed tomography (CT) era was confirmed by intraoperative X-ray pictures. With the availability of CT it is now possible to confirm the position of the probe-tip on an image of the target. For biopsy of small lesions in critical areas of the brain, permanent placement of radioactive seeds, or thalamotomy, it would be desirable to have confirmation of the site of the probe-tip prior to performing the main step of the procedure. Intraoperative CT was performed in 216 stereotactic procedures carried out on the scanner table including biopsies, aspiration of cysts, brachytherapy, aspiration of abscesses, thalamotomy, and evacuation of intracerebral hematoma. In 6 cases, inaccuracies were detected, which it was possible to correct so as to place the probe where desired.

Adolescent↗
PubMed1992

Selection of tumor cell variants for resistance to tumor necrosis factor also induces a form of pleiotropic drug resistance.

This study has addressed the question of whether there may be some common mechanism underlying the induction or expression of acquired cytokine and drug resistance in a tumor cell line. This study employed the tumor-necrosis-factor(TNF)-sensitive U937 tumor cell line as a model system to determine if selection of a tumor cell variant for cytokine resistance would also result in drug resistance and vice versa. Variants were selected by culturing in the presence of purified recombinant TNF or a mixed-lymphokine-containing supernatant derived from concanavalin-A-stimulated peripheral blood lymphocytes. The resulting variants were resistant not only to TNF, but also to certain chemotherapeutic drugs. The variants were most resistant to colchicine and the Vinca alkaloids, requiring drug concentrations 50- to 5000-fold higher to mediate levels of cytotoxicity comparable to that seen with the parental U937. The variants were moderately resistant to cycloheximide, actinomycin D, and mitomycin C. In contrast, these lines were relatively sensitive to doxorubicin or daunomycin. This phenomenon was not unique to U937 cells since we obtained a similar pattern of drug resistance by selecting TNF-resistant variants of the WEHI-164 tumor cell line. The cytokine-selected U937 variants were still lysed by NK cells, although they were somewhat less sensitive than the parental U937. Both variants were relatively resistant to lysis by activated macrophages, probably because of their TNF resistance. In an alternative selection procedure, U937 variants were derived by culturing in the presence of increasing concentrations of colchicine. The resulting variants were relatively resistant to TNF, providing further support for the existence of some common mechanism operating in induction or expression of acquired cytokine and drug resistance. The resistance mechanism apparently does not involve the P glycoprotein since the cytokine-selected U937 variants do not overexpress the mdr gene. This study has demonstrated that selection of TNF-resistant variants results in coexpression of a unique form of drug resistance that is characterized by resistance to microtubule-active drugs but not to the anthracycline antibiotics and is not associated with overexpression of the mdr gene.

Animals↗
PubMed1992

Human immunodeficiency virus type 2 envelope glycoprotein: differential CD4 interactions of soluble gp120 versus the assembled envelope complex.

Utilizing a recombinant vaccinia expression system, we investigated the biological properties and CD4 receptor interactions of the envelope glycoproteins of a noncytopathic human immunodeficiency virus type 2 strain, termed HIV-2/ST, and a highly cytopathic variant derived from it. The efficiency and host cell range of syncytium formation by the recombinant glycoproteins of both viruses were highly restricted compared to those of prototypic strains of HIV (HIV-2/ROD or HIV-1/IIIB). However, the glycoprotein of cytopathic but not wild-type ST generated numerous large syncytia in the human T-cell line Sup T1 from which it was derived. A single cell line (Molt 4 clone 8) was permissive to fusion by both wild-type and cytopathic ST envelopes, but only the glycoprotein of cytopathic ST could be inhibited with a soluble form of the viral receptor CD4 (sCD4). While these results indicated major differences in the envelope glycoprotein-CD4 receptor interactions of wild-type versus cytopathic ST, direct and competition binding assays utilizing soluble external glycoprotein (SU) and sCD4 surprisingly revealed equivalent low binding affinity for both viruses. From these experiments we conclude that relevant biological properties (e.g., CD4 binding, cytopathic potential, and sCD4 neutralization) of HIV viruses which differ in their pathogenic potential are reflected in the sCD4 interactions of the assembled native envelope complex (as on cell or virion surfaces) but not the soluble SU glycoprotein.

CD4 Antigens↗