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Biomedical subjects

S Majumdar

Publications and source records attributed to S Majumdar.

At least 19 recordsLinked to original sources
PubMed1992

Alpha-1-antichymotrypsin inhibits the NADPH oxidase-enzyme complex in phorbol ester-stimulated neutrophil membranes.

The generation of superoxide anion and release of granule contents are essential to the bactericidal function of neutrophils, but may also contribute to host tissue damage during inflammation. In previous studies (J. Immunol. 146:2388), we have demonstrated that the acute phase reactant alpha-1-antichymotrypsin (ACT), a potent inhibitor of the serine protease cathepsin G, also suppresses superoxide anion generation. The inhibitory effect of ACT was not directly linked to its antiproteolytic activity and may reflect interaction at a site other than its reactive loop. To further characterize the mechanism of inhibition, we investigated the direct effects of ACT on the NADPH oxidase enzyme complex and the signaling pathways that regulate motivation of the respiratory burst. We present evidence that ACT does not intefer with agonist-stimulated calcium mobilization or translocation and activity of protein kinase C. ACT was an effective inhibitor of superoxide anion generation in membrane preparations isolated from PMA-activated cells. These results support the notion that ACT is acting on a component of the active assembled NADPH oxidase complex. Thus, ACT may have an important role in regulation of specific aspects of the inflammatory processes and the modulation of toxic oxygen-based host tissue damage.

Arachidonic Acid↗
PubMed1992

Genes for beta-thromboglobulin and platelet factor 4 are closely linked and form part of a cluster of related genes on chromosome 4.

The small inducible gene (SIG) family encodes related proteins that are involved in the overlapping processes of coagulation, inflammation, immune response, and wound repair. This family contains two branches, termed CXC and CC, which are distinguished by whether or not the first two of four conserved cysteine residues are separated by an additional amino acid residue. All of the CXC SIGs map to chromosome 4, including those encoding beta-thromboglobulin (beta TG) and platelet factor 4 (PF4), both of which are expressed by megakaryocytes in a tissue-specific fashion. Both of these latter two genes have been previously reported to be duplicated, there being a PF4 and a PF4alt gene, and a beta TG1 and beta TG2 gene. We now show by pulse-field gel electrophoresis (PFGE) that the beta TG genes are closely linked to the PF4 genes and to other previously mapped CXC SIGs, namely IL8 (encoding interleukin-8), GRO1 (encoding a cytokine also called melanoma growth-stimulatory activity), and two related genes GRO2 and GRO3, on a single 700-kb Sfil fragment localized to chromosome bands 4q12-q13. The only CXC SIG not linked to this cluster is that encoding gamma-interferon-induced 10-Kd protein (INP10), which has been previously localized to 4q21. Analysis of lambda genomic clones demonstrate that the beta TG1 and PF4 genes are separated by less than 7 kb, and the beta TG2 and PF4alt genes by approximately 5 kb. Within each beta TG/PF4 duplication, the beta TG-like gene is upstream of its linked PF4-like gene. Thus, the beta TG/PF4 genes appear to form a close-linked complex expressed in a megakaryocyte-specific fashion. Further genomic studies may provide additional insights into the regulation of the tissue-specific expression of the beta TG/PF4 gene complex, while further analysis of the linked CXC SIG cytokine family may provide further understanding of their evolutionary history.

Autoradiography↗
PubMed1992

Calcium transport and Ca(++)-ATPase activity in spermatozoal plasma membrane vesicles of nifedipine-administered guinea pigs.

Spermatozoal plasma membrane vesicles isolated from distal portion of the epididymis and vas deferens were found to contain Ca(++)-activated ATPase and calcium transport activities. Nifedipine was administered at two different doses (1.0 and 2.5 mg/kg b.w./day) and the effect was observed for both short- (4 week) and long-term (12 week) period. The cellular ionic calcium content and Ca(++)-ATPase activity were observed to be enhanced in the drug-treated animals. The recovery studies carried out after 4 and 6 weeks of withdrawal of the drug treatment exhibited partial to complete restoration of observed changes. The stimulatory rather than inhibitory effect of Nifedipine, a specific calcium channel blocker, on calcium uptake may suggest that voltage-sensitive calcium channels may be lacking in guinea pig spermatozoa. The stimulatory effect of the drug is speculated to be either by inhibition of Na(+)-Ca++ antiporter or G-protein activated agonistic effect or probably due to altered physicochemical properties of the drug-treated sperm plasma membranes.

5'-Nucleotidase↗
PubMed1992

[Residual and reconverted hematopoietic bone marrow in the distal femur. Spin-echo and opposed-phase gradient-echo MRT].

The distal femur contains usually only fatty marrow in the adult. We investigated the incidence of areas of residual and reconverted hematopoietic marrow in the distal femur in a series of 50 adult patients using conventional spin-echo and opposed-phase gradient-echo MR images. Zones with intermediate to low signal intensity in both sequences representing hematopoietic marrow within high signal intensity fatty marrow were observed in 17 of the 50 patients. Opposed-phase gradient-echo sequences demonstrated significantly greater red-yellow marrow contrast than conventional spin-echo sequences. Residual red marrow may represent a biologic variation of the normal adult pattern of red-yellow marrow distribution in women of menstruating age. Reconverted red marrow appears to be related to increased erythrocyte demand. It should not be mistaken for bone marrow malignancy. Absence of epiphyseal involvement, cortical destruction and soft-tissue mass in residual and reconverted hematopoietic marrow are helpful differential criteria.

Adult↗
PubMed1992

Efficacies of liposome-encapsulated streptomycin and ciprofloxacin against Mycobacterium avium-M. intracellulare complex infections in human peripheral blood monocyte/macrophages.

Current treatments of disseminated infection caused by the Mycobacterium avium-M. intracellulare complex (MAC) are generally ineffective. Liposome-mediated delivery of antibiotics to MAC-infected tissues in vivo can enhance the efficacy of the drugs (N. Düzgüneş, V. K. Perumal, L. Kesavalu, J. A. Goldstein, R. J. Debs, and P. R. J. Gangadharam, Antimicrob. Agents Chemother. 32:1404-1411, 1988; N. Düzgüneş, D. A. Ashtekar, D. L. Flasher, N. Ghori, R. J. Debs, D. S. Friend, and P. R. J. Gangadharam, J. Infect. Dis. 164:143-151, 1991). We investigated the therapeutic efficacies of liposome-encapsulated streptomycin and ciprofloxacin against growth of the MAC inside human peripheral blood monocyte/macrophages. Treatment was initiated 24 h after infection of macrophages with the MAC and stopped after 20 h, and the cells were incubated for another 7 days. The antimycobacterial activity of streptomycin was enhanced when the drug was delivered to macrophages in liposome-encapsulated form, reducing the CFU about threefold more than the free drug did throughout the concentration range studied (10 to 50 micrograms/ml). With 50 micrograms of encapsulated streptomycin per ml, the CFU were reduced to 11% of the initial level of infection. Liposome-encapsulated ciprofloxacin was at least 50 times more effective against the intracellular bacteria than was the free drug: at a concentration of 0.1 microgram/ml, liposome-encapsulated ciprofloxacin had greater antimycobacterial activity than the free drug at 5 microgram/ml. With liposome-encapsulated ciprofloxacin at 5 micrograms/ml, the CFU were reduced by more than 1,000-fold at the end of the 7-day incubation period, compared with untreated controls. These results suggest that liposome-encapsulated ciprofloxacin or other fluoroquinolones may be effective against MAC infections in vivo.

Ciprofloxacin↗
PubMed1992

Interaction of Vibrio cholerae cells with beta-lactam antibiotics: emergence of resistant cells at a high frequency.

Unlike other gram-negative enteric bacteria, Vibrio cholerae cells were equally susceptible to penicillin and ampicillin and in general more susceptible than Escherichia coli to most of the beta-lactam antibiotics. The turbidity of penicillin-treated cultures contained to increase exponentially for about 3 h, although the cell viability declined rapidly within 30 min of penicillin addition. Prolonged treatment with beta-lactam antibiotics produced cells resistant to these antibiotics. A fluctuation test indicated that this resistance might be due to adaptive mutation. Cells resistant to a beta-lactam exhibited broad cross-resistance to other beta-lactam antibiotics. A new 12,000-Da outer membrane protein was detected both in beta-lactam-resistant cells and in wild-type cells growing in medium containing beta-lactam antibiotics. While the penicillin-resistant cells had all of the penicillin-binding proteins (PBPs) present in the parental cells, significant differences in the relative proportion of low-molecular-weight PBPs were seen. The low-molecular-weight PBPs from resistant cells seemed to form more stable complexes with penicillin than those from the parental strain.

Anti-Bacterial Agents↗
PubMed1992

Lactic acidosis: effect of treatment on intracellular pH and energetics in living rat heart.

Systemic acidemia may impair cardiac contractility and predispose to arrhythmias. Moreover, bicarbonate treatment may further depress cardiac performance and increase mortality. Whether changes in myocardial intracellular pH or energy metabolism underlie this diminished performance has not been clarified in the in vivo setting. Thus we investigated the effect of lactic acidosis and two proposed treatments on myocardial energetics and intracellular pH in anesthetized living rats. A previously validated 31P-labeled nuclear magnetic resonance (31P-NMR) spectroscopic technique using saturating pulses was used to follow myocardial intracellular pH, phosphocreatine (PCr), ATP, and inorganic phosphate (Pi). After obtaining baseline values, we infused lactic acid to achieve a level greater than 5 mM. We then added an infusion of either bicarbonate (n = 7) or saline (n = 5). During lactic acid infusion, arterial pH declined (from 7.27 to 7.07, P less than 0.0001), but myocardial intracellular pH did not change (7.13 vs. 7.07, P not significant). The ratio of PCr to Pi, however, decreased with acidemia (from 3.13 to 2.24, P = 0.004), suggesting impaired energy metabolism. Compared with saline, bicarbonate infusion restored systemic pH (from 7.08 to 7.29), but myocardial pH was unaltered. In addition, PCr/Pi declined further following bicarbonate treatment (1.41 vs. 2.42, P = 0.08) but not following saline. Thus, despite reversal of systemic acidemia, bicarbonate treatment was associated with more severe impairment of energy metabolism than saline. This suggests a mechanism for previously reported adverse cardiac effects of bicarbonate treatment.

Acidosis, Lactic↗
PubMed1992

T lymphocytes and activated eosinophils in airway mucosa in fatal asthma and cystic fibrosis.

With the use of monoclonal antibodies (mAb) and immunohistology, the numbers of phenotypically distinct cells infiltrating lung tissue from 15 postmortem (PM) cases of fatal asthma were quantified and compared with 6 cases of cystic fibrosis (CF) (three postmortem, three transplant) and 10 nonasthmatic cases of sudden death matched for age and sex. Tissue eosinophilia was significantly greater (p less than 0.001) in the fatal asthma group than in the CF or sudden death controls. In asthma, approximately 40% of the eosinophilic infiltrate was EG2 positive (an indication of eosinophil activation and secretion of eosinophil cationic protein). The numbers of eosinophils and EG2 positive cells were significantly elevated in the subjects with acute severe asthma who had had a duration of terminal illness exceeding, as compared with less than, 24 h (p less than 0.05). When compared with the sudden death controls, there were increases in the numbers of Dako L C positive cells (i.e., CD45 positive "total leukocytes") in both fatal asthma and CF (p less than 0.01 and 0.05, respectively). The mean number of MT-1 positive (T) cells in the asthma and CF groups was approximately twice that of the control (p less than 0.05 and 0.01, respectively). The mean number of MB2 positive (B) cells was similar for both the asthma and sudden death control groups but was significantly increased in CF (p less than 0.05). The average T:B cell ratios were 6:1, 1:1, and 2:1 in the fatal asthma, CF, and control groups, respectively. The results support a role for the T lymphocyte in the pathogenesis of fatal asthma and CF.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗
PubMed1992

Immunoassay for the determination of surfactant apoprotein (SP-A) in human amniotic fluid: comparison with other indices of assessing foetal lung maturity.

The concentration of the major surfactant-associated protein SP-A (28-36 kDa) was determined in 73 amniotic fluid samples obtained from normal (n = 40) and complicated (n = 33) pregnancies. Lecithin/sphingomyelin (L/S) ratio and phosphatidylglycerol (PG) levels were also determined in all the samples by one-dimensional step-wise thin-layer chromatography. An enzyme-linked immunosorbent assay was used to determine human lung surfactant apoprotein SP-A. The amount of SP-A in human amniotic fluid increased as a function of gestational age from 8 mg l-1 at 36 weeks to 11.75 mg l-1 at 40-41 weeks of gestation. There was a significant difference (p less than 0.01) in amniotic fluid SP-A concentration from female (9.93 +/- 0.60 micrograms ml-1) compared to male (9.10 +/- 0.52 micrograms ml-1) foetuses. In amniotic fluid samples obtained from a group of complicated pregnancies, SP-A levels were significantly lower than in the normal group when adjusted for gestational age and sex of the foetus (p less than 0.05).

Amniotic Fluid↗