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Biomedical subjects

M S Kumar

Publications and source records attributed to M S Kumar.

At least 73 records · Page 4Linked to original sources
PubMed1990

Disulfiram administration affects substance P-like immunoreactive and monoaminergic neural systems in rodent brain.

The biosynthetic enzyme peptidylglycine alpha-amidating monooxygenase catalyzes the formation of a variety of biologically active alpha-amidated peptides from respective COOH-terminal glycine-extended peptide precursors. Peptidylglycine alpha-amidating monooxygenase activity is dependent on copper, ascorbate, and molecular oxygen and is inhibited by the relatively selective copper chelator N,N-diethyldithiocarbamate or its disulfide dimer disulfiram (Antabuse). In the present study, chronic disulfiram treatment (100 mg/kg/day, for 12-25 days) resulted in significant changes in several neurochemical parameters in the mouse central nervous system, including levels of substance P-like, unamidated substance P-Gly-like, and protease-generated substance P-Gly-Lys-like immunoreactivities (SP-LI, SP-G-LI, and SP-G-K-LI, respectively). Combined high performance liquid chromatography/radioimmunoassay analyses of the extracted SP-LI, SP-G-LI, and SP-G-K-LI species indicated very similar chromatographic and immunochemical behavior as demonstrated for chemically authentic peptide standards. Additionally, changes in levels of monoamines and their metabolites were observed after drug administration. Complementary immunohistochemical analyses using affinity-purified anti-SP-G sera localized these drug-induced changes in levels of immunoreactive unamidated precursor to neural elements that normally express SP. As a functional corollary to alterations in neurochemical parameters, we observed significant disulfiram-induced increases in pain thresholds, potentiated by capsaicin treatment. Overall, our results indicate that the observed changes in steady state levels of immunoreactive SP and of the immature COOH-terminal extended forms of SP may reflect compensatory biosynthetic and posttranslational processing events in SP-containing neural systems after pharmacological challenge.

Amino Acid Sequence↗
PubMed1990

Interleukin 1 stimulation of the hypothalamic-pituitary-adrenal axis.

The effect of varying doses of purified human interleukin 1 (IL-1) on rectal temperature (Tr), hypothalamic corticotropin-releasing hormone (CRH), pituitary and plasma adrenocorticotropic hormone (ACTH), and plamsa corticosterone was examined in intact male rats at 24 degrees C; plasma ACTH and corticosterone responses were also studied in hypophysectomized rats. In addition, IL-1-induced changes in corticosterone concentration were investigated by means of adrenal organ cultures. Tr was measured with thermocouples. CRH and ACTH levels were determined by radioimmunoassay, and corticosterone by protein-binding assay. Intravenous administration of IL-1 (0.063-1.0 ng) resulted in hyperthermia, which began 20 min postinjection and continued for an additional 30 min. IL-1 at a dose of 0.5 ng resulted in no change in hypothalamic CRH, pituitary ACTH, or plasma ACTH levels compared with saline-treated rats. Plasma corticosterone was significantly (P less than 0.05) elevated 30 min after IL-1 administration and returned to control levels after 1 h. The higher dose of IL-1 (1.0 ng) did not affect hypothalamic CRH content, but pituitary ACTH began to rise at 15 min and was significantly (P less than 0.05) elevated 30 min after injection. Rats receiving this dose displayed elevated (P less than 0.05) plasma ACTH and corticosterone levels 30 and 60 min postinjection. No change in plasma corticosterone was observed in hypophysectomized rats administered either 1 ng of IL-1 or 1 microgram of recombinant IL-1 beta (rIL-1 beta); adrenal organ cultures treated with IL-1 (10(-11) M) responded similarly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1988

Analgesia in defeated mice: evidence for mediation via central rather than pituitary or adrenal endogenous opioid peptides.

Mice subjected to defeat in a social conflict paradigm display an analgesic response that is apparently mediated by endogenous opioids. It is blocked by naloxone and shows full cross-tolerance to and from morphine. The present study investigated the contribution of sources of endogenous opioids outside of the central nervous system, namely the pituitary and adrenal glands. Treatment known to enhance (metyrapone pretreatment), reduce (2% saline in the drinking water) or block (dexamethasone pretreatment) the release of beta-endorphin from the anterior pituitary did not affect the display of analgesia in defeated mice. Similarly, treatments known to enhance (reserpine pretreatment) or block release of enkephalins (removal of the adrenals or hexamethonium pretreatment) from the adrenal medulla also failed to influence defeat-induced analgesia in the expected manner. If anything, adrenalectomy enhanced and reserpine pretreatment suppressed the analgesic response to defeat. The data are discussed in terms of providing evidence that defeat-induced analgesia is mediated primarily by endogenous opioids released and acting within the central nervous system.

Animals↗
PubMed1988

Characterisation of blast cells during blastic phase of chronic myeloid leukaemia by immunophenotyping--experience in 60 patients.

The blast cell population of 60 patients with chronic myeloid leukaemia in blast crisis (CML-BC) were analyzed with a panel of monoclonal antibodies to determine the cell surface antigen phenotypes. In addition, cytochemical stains periodic acid Schiff (PAS), myeloperoxidase (MP), Sudan black B (SBB) and terminal deoxynucleotidyl transferase (TdT) were also utilized for subtyping. Nineteen cases (31.6%) expressed lymphoid phenotypes characteristic of common ALL cells and one case with extramedullary lymph node crisis expressed T-cell surface phenotypes. Thirty cases (50%) expressed solely myelomonocytic surface antigens with significant TdT activity in three. Cytochemical stains contributed to recognize only 57% of these myeloid blasts. Seven cases (11.7%) were with a mixture of heterogenous group of cells expressing phenotypic characteristics for various haemopoietic cells of different lineage--five of them from the cells of non-lymphoid series (myelomono-erythromegakaryocytic series) and the other two with cells from both lymphoid and myeloid series. Additionally, in two cases (3.3%), the precursor cells reacted only with the erythroid monoclonals. Finally, in one case, the blast cells remained unclassified due to nonreactivity with any of the monoclonals used but expressed significant TdT positivity. The response to uniform vincristine and prednisolone (V + P) therapy has shown that lymphoid blast crisis cases were highly responsive in contrast to the cases with non-lymphoid blast crisis (complete remission rate 86 vs 21.4%). The results confirm the evidence of multilineage blast crisis involving either single or mixed haemopoietic differentiation pathway and the utility of having phenotypic characterisation for designing protocols for chemotherapy in the CML patients at the time of blast crisis.

Adolescent↗