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Biomedical subjects

V Kumar

Publications and source records attributed to V Kumar.

At least 73 records · Page 4Linked to original sources

Accidental poisoning in south west Maharashtra.

A retrospective analysis of accidental poisoning (oral and parenteral) in children admitted to the Pediatric Ward of Krishna Hospital and Medical Research Centre, Karad over the past five years (1984-1988) was done. Overall incidence of accidental poisoning in children was 1.8% (oral 1%, parenteral 0.8%). Mean age of children was 6.5 years, with male-female ratio 2:1. Oral poisoning was more common in children below 5 years whereas parenteral poisoning was common in children above 5 years. Kerosene oil was the commonest oral poison (30%). Oral poisoning was more common in summer (61%) and parenteral in the rainy season (51%). Rural children were more commonly involved than urban children (ratio being 5:2). Gastrointestinal symptoms were commoner with oral poisons. No mortality was noted with oral poisons; 3% children died due to snake bite.

Accidents

Lasers in pulmonology.

Lasers have multiple applications in pulmonary medicine. The Nd: Yag laser is at present widely accepted for the management of respiratory problems. The major indications are central tracheobronchial obstruction due to neoplasms, uncontrolled haemorrhage from malignant lesions and tracheal stenosis. Its role is entirely palliative and only occasionally curative. Two main complications are perforation and bleeding. The basic concepts, techniques and use in various respiratory problems are discussed.

Bronchial Neoplasms

Differential effects of dehydroepiandrosterone (DHEA) on murine lymphopoiesis and myelopoiesis.

Dehydroepiandrosterone (DHEA) inhibits murine lymphopoiesis, especially after sublethal irradiation, without affecting mature lymphocyte function. We demonstrate here that dietary DHEA differentially affected myelopoiesis and lymphopoiesis in sublethally irradiated mice. Erythropoietic progenitor cell and stem cell function was not affected by DHEA although the magnitude of granulopoiesis was slightly reduced. Regeneration of marrow B220+ B cells, natural killer (NK) function, and thymus repopulation were significantly delayed in DHEA-fed mice. Interleukin 2 (IL-2) failed to restore NK activity of DHEA-fed mice to normal levels. Marrow from DHEA-fed mice contained competent thymocyte progenitors capable of repopulating thymi of irradiated hosts fed a control diet but not those fed the DHEA diet. Thus DHEA inhibits lymphopoiesis while sparing myelopoiesis, affecting the growth and maturation of T, B, and NK cells by a mechanism other than the inhibition of IL-2 production.

Animals

NADPH oxidase activity in the monocytes and neutrophils of patients with rheumatic fever.

The enzyme NADPH oxidase is involved in the production of oxygen free radicals. We measured its activity in neutrophils and monocytes obtained from patients with acute rheumatic fever, chronic rheumatic heart disease, acute streptococcal pharyngitis and normal controls. Follow up studies were made at 15 days, 3 months and 6 months. Streptococcal membrane antigen, carbohydrate antigens and latex were used to stimulate the oxidative activity in the neutrophils and monocytes. These three agents caused a significant increase in the enzyme activity of the phagocytes of patients with acute rheumatic fever and chronic rheumatic heart disease (p less than 0.001) but not in acute pharyngitis. Maximal NADPH oxidase enzyme activity was observed in patients with acute rheumatic fever. During the follow-up, there was a significant decline in the enzymatic activity in patients with acute rheumatic fever but not in those with chronic rheumatic heart disease. Enzymatic activity was greater when the phagocytic cells were triggered with membrane as compared to carbohydrate antigen and latex in all the groups and at all intervals. The enzymatic response of neutrophils and monocytes was similar although the magnitude of the NADPH oxidase activity was significantly higher in neutrophils than in monocytes.

Adult

Treatment of Alzheimer's disease with cholinergic drugs.

Several cholinergic drugs have been experimentally used to treat the cognitive and behavioral deficits associated with Alzheimer's disease. Unfortunately the results have been somewhat disappointing. The cholinergic drugs are also prone to produce serious side effects. Experience with these drugs lead us to conclude that cholinergic drugs alone may not be the answer to treat Alzheimer disease patients. There seems to be a need to develop drug(s) which could affect several neurotransmitter or neuromodulator systems. Neuroendocrine changes induced by these drugs may be useful biological markers in estimating their central effects.

Alzheimer Disease

Oligonucleotides, part 5+: synthesis and fluorescence studies of DNA oligomers d(AT)5 containing adenines covalently linked at C-8 with dansyl fluorophore.

The synthesis of oligodeoxynucleotides d(AT)5 in which specific adenines are linked at C-8 position with dansyl fluorophores via a variable polymethylene spacer chain are reported. This was achieved by a strategy involving prelabelling at the monomeric stage followed by solid phase assembly of oligonucleotides to obtain regiospecifically labeled oligonucleotides. Several mono and polydansyl d(AT)5 derivatives in which the fluorophore is linked via ethylene, tetramethylene and hexamethylene spacer arms were synthesised for a systematic study of their fluorescence characteristics. It was observed that (i) enhancements in fluorescence intensity and emission quantum yields are seen due to multiple labelling, (ii) the magnitude of enhancements are related to labelling configuration and (iii) quenching efficiency is minimal with shorter and rigid spacer arms. The results may aid rational design of multiple fluorescent DNA probes for nonradioactive detection of nucleic acids.

Adenine

An absence of T cells in murine bone marrow allografts leads to an increased susceptibility to rejection by natural killer cells and T cells.

The mechanisms behind the increased incidence of marrow graft failure in recipients that receive allogeneic marrow depleted of T cells were studied. Recipient mice were lethally irradiated and challenged with bone marrow cells (BMC) from C.B-17 +/+ (+/+) donors. Radioisotope 125IUdR incorporation was assessed 5 to 7 days after transfer to determine the extent of engraftment. Some groups received BMC in which the T cells were removed by treatment with antibody and C. In addition, some groups received BMC from T cell-deficient C.B-17 scid/scid (SCID) mice to determine the postulated need for donor T cells in hematopoiesis and engraftment. In a model system that distinguishes between possible host NK cell and radioresistant T cell-mediated rejection of marrow allografts, it was determined that the absence of donor T cells in a marrow graft does not affect engraftment in syngeneic recipients. However, both host NK cell and radioresistant T cell rejection was markedly enhanced when SCID BMC or BMC from C.B-17 +/+ donors that had T cells removed by antibody and complement were infused into irradiated allogeneic recipients. Furthermore, the addition of alloreactive thymocytes as a source of T cells could abrogate this increased susceptibility of the BMC to host rejection mechanisms. As determined by histology and 59Fe uptake, the addition of thymocytes resulted in enhanced erythropoiesis. These results suggest that the increased incidence of marrow graft failure when BMC depleted of T cells are used is a result of active rejection by host effector cells and that the adverse effect of marrow T cell depletion can be reversed by the addition of thymocytes.

Animals

cis-acting negative regulatory element of prolactin gene.

The prolactin (PRL) gene in clonal strains of rat pituitary tumor cells in culture (GH cells) exhibit several regulatory responses, similar to the ones observed in rat pituitary gland. A comparative analysis of regulation of PRL gene expression in PRL-producing (PRL+) and PRL-nonproducing (PRL-) GH cells was conducted by monitoring the PRL promoter driven transient expression of chloramphenicol acetyltransferase (CAT) gene in GH4C1 (PRL+) and GH12C1 (PRL-) cells. The PRL promoter activity was drastically inhibited only in PRL-nonproducing cells (PRL-) and not in PRL producing cells (PRL+) when a 80-base pair (bp) DNA sequence from 5'-flanking region of PRL gene (located between -330 and -250 bp) was included in the PRL-CAT fusion gene constructs. Furthermore, a DNA/protein interaction involving this 80-bp DNA sequence and a 60-kDa nuclear protein was detected only in PRL- cells but not in PRL+ GH cells. These results suggested that the strain-specific suppression of PRL gene in PRL-, GH12C1 cells was mediated via interaction of a cis-acting negative regulatory element with a negative regulatory trans-acting factor in these cells. The negative regulatory element within the AT-rich 80-bp DNA sequence was mapped immediately adjacent to the site of interaction of trans-activators of PRL gene.

Animals

Natural killer cells in the thymus. Studies in mice with severe combined immune deficiency.

The relationship between NK cell and T cell progenitors was investigated by using mice with severe combined immune deficiency (scid). Scid mice are devoid of mature T and B cells because they cannot rearrange their Ig and TCR genes. However, they have normal splenic NK cells. Thymus of scid mice, although markedly hypocellular, contains cells that lyse YAC-1, an NK-sensitive tumor cell. By flow cytometry, two populations of cells were identified in the scid thymus. Eighty percent of the cells were Thy-1+, IL-2R(7D4)+, J11d+, CD3-, CD4-, CD8- whereas the remaining were IL-2R-, J11d-, CD3-, CD4-, and CD8-. By cell sorting, all NK activity was found in the latter population, which is phenotypically similar to splenic NK cells. To determine if the thymus contains a bipotential NK/T progenitor cell, J11d+, IL-2R+ cells were cultured and analyzed for the generation of NK cells in vitro. These cells were used because they resemble 15-day fetal and adult CD4- CD8- thymocytes that are capable of giving rise to mature T cells. Cultured J11d+ thymocytes acquired non-MHC-restricted cytotoxicity, but in contrast to mature NK cells, the resulting cells contained mRNA for the gamma, delta, and epsilon-chains of CD3. This suggests that J11d+ cells are early T cells that can acquire the ability to kill in a non-MHC-restricted manner, but which do not give rise to NK cells in vitro. The differentiative potential of scid thymocytes was also tested in vivo. Unlike bone marrow cells, scid thymocytes containing 80% J11d+ cells failed to give rise to NK cells when transferred into irradiated recipients. Together these results suggest that mature NK cells reside in the thymus of scid mice but are not derived from a common NK/T progenitor.

Animals

Natural killer cells activated with interleukin 2 in vitro can be adoptively transferred and mediate hematopoietic histocompatibility-1 antigen-specific bone marrow rejection in vivo.

An adoptive transfer model was developed for examining natural killer (NK) cell-mediated bone marrow cell (BMC) graft rejection. Homogeneous populations of NK cells were obtained by culturing spleen cells from mice with severe combined immune deficiency in the presence of recombinant interleukin 2 for 7 days. These cells maintained a phenotypic (CD3-CD4-CD8-NK-2.1+ and asialo GM1+) and lytic pattern consistent with that of activated NK cells. The cells were infused into lethally irradiated recipients whose own NK cells were depleted by anti-NK-1.1 antibody treatment and could no longer reject marrow allografts. The transferred NK cells restored the ability of the hosts to reject BMC in a hematopoietic histocompatibility-1 (Hh-1) antigen-specific manner. Immunogenetic studies demonstrated that the rejection was a function of the donor, not host, NK cells. These studies demonstrate that NK cells can be cultured in vitro with recombinant interleukin 2 and are capable of mediating Hh-1-specific BMC rejection in vivo in the absence of other immune cell types.

Animals

Androgen, estrogen, and progesterone receptor contents and serum hormone profiles in patients with benign hypertrophy and carcinoma of the prostate.

Cytosolic and nuclear androgen, estrogen and progesterone receptor content was measured in the groups of 11 prostatic carcinoma (PCA) and 32 benign prostatic hypertrophy (BPH) samples. All BPH cases were positive for the cytosolic progesterone (PRc) and estrogen receptor (ERc), whereas only 85% of cases (23/27) contained the androgen receptor (ARc). Only those five patients who received estrogen treatment in the PCA group had detectable ARc. PRc was present in all of the PCA cases, whereas ERc could be detected in only 82% (9/11) of cases. Cytosolic contents of all three steroid receptors, however, were higher in the PCA group. The level of nuclear steroid receptors, although present in fewer cases in both groups, was higher than the cytoplasmic receptors. The serum profile of estradiol, cortisol, and prolactin was normal in both groups, whereas LH, FSH, and progesterone levels were higher than in normal adults. Serum testosterone level was within normal range in the BPH group, but it was significantly below normal (P less than 0.005) in PCA patients.

Aged

Stratum corneum antibodies detected by hemagglutination are not directed against keratin intermediate filaments.

Autoantibodies to stratum corneum (SC) occur in virtually all normal adult human sera. These antibodies may be directed against various antigens of the SC. They have been detected by indirect immunofluorescence, passive hemagglutination (HA), immune adherence, and most recently by enzyme immunoassay and immunoblot methods. The purpose of our study was to examine whether antibodies to SC antigens as detected by passive HA are similar to the keratin intermediate filament (KIF) reactive antibodies. SC antigen preparation was prepared from psoriatic scales by the trypsin-phenol-water (TPW) extraction method. KIFs were prepared by 8 M urea extraction of normal callus or psoriatic scales. The anti-SC antibody titers of normal human sera were determined by passive HA before and after absorption with TPW-SC antigen preparation and upon absorption with KIFs. Similarly, titers of anti-KIF antibodies were determined on absorbed and unabsorbed sera by immunoblot assay. The results of this study indicate that the absorption of the sera with KIFs did not affect the titer of antibodies to TPW-extractable SC antigens whereas the titer of KIF antibodies dropped. KIF-reactive antibodies, on the other hand, were not affected by absorption with TPW-SC antigen, whereas the latter absorbed out the corresponding reactive antibodies. These results indicate that antibodies directed against SC antigen are different from the KIF-reactive antibodies.

Amino Acids

Placental transfer of metals of coal fly ash into various fetal organs of rat.

Fly ash (100 mg/kg body weight) was administered intratracheally to 14-day pregnant rats for 6 consecutive days. On day 20 of gestation the translocation of metals present in the fly ash to various maternal and fetal organs was studied. Fly ash administration to pregnant mothers retarded the growth of fetal heart and kidney as determined by their weights. Fly ash instillation increased organ levels of nearly all the metals studied in both mother and fetus. Most of the metals present in coal fly ash were transferred in significant amounts through placenta to several fetal organs. However, the pattern of their distribution into various fetal organs was different for different metals.

Animals

Role of oxygen free radicals generated by blood monocytes and neutrophils in the pathogenesis of rheumatic fever and rheumatic heart disease.

The generation of oxygen free radicals by peripheral blood monocytes and neutrophils of patients with rheumatic fever and rheumatic heart disease has been studied using luminol enhanced chemiluminescence technique. Five groups of patients; acute rheumatic fever, recurrence of rheumatic activity, chronic rheumatic heart disease, acute pharyngitis and normal controls were studied. In all groups except the controls, measurements were made on 0, 15, 90 and 180 days. The chemiluminescence was measured in response to streptococcal membrane antigen, carbohydrate antigen and latex as triggering agents. Chemiluminescent response of monocytes, as well as, neutrophils was significantly higher (P less than 0.01) in acute rheumatic fever and recurrence of rheumatic heart disease as compared to patients with acute pharyngitis and chronic rheumatic heart disease through the study period and with all the triggering agents. A significant decline (P less than 0.001) in chemiluminescence was observed from day 0 to day 180 in the acute rheumatic fever, recurrence of rheumatic heart disease and pharyngitis patients while no such change, was observed in the chronic rheumatic heart disease group. This study raises the possibility that these phagocytic cells, which infiltrate the myocardium, may have a role in the pathogenesis of cardiac disease seen in patients with rheumatic heart disease, through the generation of oxygen free radicals.

Acute Disease

Chronic ulcerative stomatitis associated with a specific immunologic marker.

Four elderly women with chronic oral ulcerations are described. The lesions are chronic, erosive, or ulcerative; occur on the gingival, buccal, or lingual mucosa; and may occur in the form of desquamative gingivitis. The histopathologic findings are nondiagnostic. The disease is refractory to local and systemic corticosteroids, but treatment with hydroxychloroquine may be effective. Both in vivo binding to the oral mucosa and skin of a stratified epithelium-specific antinuclear antibody and high titers of these antibodies in serum are markers of this disease, which we refer to as chronic ulcerative stomatitis associated with stratified epithelium-specific antinuclear antibody.

Aged

Direct immunofluorescence studies of sodium chloride-separated skin in the differential diagnosis of bullous pemphigoid and epidermolysis bullosa acquisita.

Bullous pemphigoid and epidermolysis bullosa acquisita may have indistinguishable clinical, histologic, and routine immunohistologic features. In those cases these two diseases can be reliably distinguished in routine diagnostic studies only in seropositive cases by tests on lamina lucida-split skin and in research studies by direct immunoelectron microscopy or, in patients with circulating autoantibodies, by immunoblotting studies. The use of these methods is limited by the expense and unavailability of the methods, the requirement for circulating autoantibodies, or both. We describe a method to distinguish between the two diseases on the basis of findings of direct immunofluorescence of a biopsy specimen after separation through the lamina lucida with 1.0 mol/L sodium chloride. The IgG appeared in the dermal side of the split specimens in epidermolysis bullosa acquisita and predominantly or exclusively in the epidermal side in pemphigoid. The method was found to be relatively simple, inexpensive, applicable to specimens preserved in transport media, and 100% reliable in our group of 22 patients.

Basement Membrane