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Biomedical subjects

A B Mukherjee

Publications and source records attributed to A B Mukherjee.

At least 91 records · Page 5Linked to original sources
PubMed1990

Determination of sex chromosomal constitution and chromosomal origin of drumsticks, drumstick-like structures, and other nuclear bodies in human blood cells at interphase by fluorescence in situ hybridization.

The sex chromosomal constitution has been determined in various types of human leukocytes at interphase by use of fluorescence in situ hybridization with X- and/or Y-specific DNA probes. It is found that during aging and differentiation of myelocytes into polymorphs there is no significant change in the relative frequency of various types of male and female cells with a specific type of sex chromosomal constitution. Non-random variability of the relative proximity between the X chromosomes within the nuclei is also observed in female cells. Moreover, we are the first to determine that sex-specific "drumsticks" and "sessile nodules" in female polymorphs originate from the X chromosomes and that non-sex-specific "drumstick-like" bodies in male polymorphs are of Y chromosomal origin.

Cell Nucleus↗
PubMed1989

Novel peptides derived from a region of local homology between uteroglobin and lipocortin-1 inhibit platelet aggregation and secretion.

The active site for uteroglobin inhibition of phospholipase A2 has been localized to a nonapeptide (P1) which is partially homologous to a nonapeptide (P2) in lipocortin, which also inhibits phospholipase A2. P1 and P2 share an identical tetrapeptide (P4) which is required for inhibition, although P4 alone does not inhibit this enzyme. We found the mechanism of inhibition of platelet aggregation and secretion by the nonapeptides and P4 varied depending on whether platelets were thrombin- or ADP-activated. All three peptides decrease thrombin esterolytic activity and thereby inhibit thrombin-induced platelet activation. P1 decreases ADP-induced aggregation and serotonin secretion by inhibiting phospholipase A2 whereas P4 decreases only aggregation by blocking fibrinogen binding to activated platelets. The P4 sequence in P1 may affect the interaction of P1 with platelets since the presence of P4 potentiates P1 inhibition of platelet activation.

Adenosine Diphosphate↗
PubMed1989

Thiamine deficiency in utero alters response to ethanol in adulthood.

To determine whether prenatal thiamine deficiency, a frequent concomitant of alcoholism, reduces the response to ethanol during adulthood in the rat as does ethanol exposure in utero (Abel et al. 1981), pregnant Sprague-Dawley rats received either control or thiamine deficient diets together with daily injections of the thiamine antagonist pyrithiamine. At 7 months of age, male offspring were exposed to precisely regulated ethanol vapor concentrations in an inhalation chamber for 24 h and blood ethanol concentrations (BECs) and ethanol-induced intoxication were determined. Prenatally thiamine deficient rats and controls were indistinguishable in terms of appearance, body and liver weights, and the ratios of liver to body weight and brain to liver weight. However, total body water was significantly greater, and BECs and behavioral impairment were decreased, in the experimental rats. These findings indicate that prenatal thiamine deprivation is associated with reduced pharmacologic effect of ethanol as a result of increases in its volume of distribution and rate of metabolism.

Animals↗
PubMed1989

Detection of a uteroglobin-like phospholipase A2 inhibitory protein in the circulation of rabbits.

Uteroglobin (UG) or blastokinin is a steroid-dependent low molecular weight secretory protein in the rabbit. This protein has many immunomodulatory properties. Recently, UG has been reported to be a potent phospholipase A2 (E.C. 3.1.1.4) inhibitor and this property may explain, at least in part, the immunomodulatory/antiinflammatory effects of this protein. Although UG has been detected in many reproductive and non-reproductive tissues of the rabbit it has not been reported in the circulation of this animal. Here, we present biochemical and immunochemical evidence for the presence of a low molecular weight circulating protein with progesterone binding and phospholipase A2 inhibitory properties similar to rabbit uterine UG. The major organs which contribute UG-like protein in circulation seem to be the tracheobronchial tree and to a lesser extent the uterus. The concentration of this protein is much higher in the vicinity of these organs as compared to peripheral circulation. Phospholipase A2 (PLA2)-catalyzed reaction is the major pathway of arachidonic acid production from cell membrane phospholipids. Arachidonic acid participates in the stimulation of guanylate cyclase, adenylate cyclase, protein kinase C and release of calcium from intracellular stores. These processes are thought to be involved in cellular signal transduction. Arachidonic acid is also essential for eicosanoid synthesis and many eicosanoids (e.g. prostaglandins, leukotrienes, etc.) are proinflammatory. Thus, the UG-like protein by inhibiting PLA2 may play a vital role in the regulation of cellular signal transduction, control of inflammation and platelet aggregation.

Animals↗
PubMed1988

Novel anti-inflammatory peptides from the region of highest similarity between uteroglobin and lipocortin I.

Significant future developments in the effective treatment of inflammatory diseases may arise from non-toxic dual inhibitors of both cyclooxygenase and lipoxygenase pathways in the arachidonate cascade. Inhibition of phospholipase A2(PLA2)(EC3.1.1.4), may provide such a dual action and recent research has concentrated on the role of PLA2-inhibitory proteins as possible anti-inflammatory agents. Blastokinin or uteroglobin is a steroid-induced rabbit secretory protein with PLA2-inhibitory activity. Its biochemical and biological properties have been extensively studied and its crystallographic structure has been resolved at 1.34 A (refs 15, 16). Lipocortins are a family of related proteins, which, it has been suggested, mediate the anti-inflammatory effects of glucocorticoids (for a review, see ref. 23). Some proteins of this group have been purified and the complementary DNA sequences of two human lipocortins are known. Lipocortins inhibit PLA2 in vitro, although their mechanism of action is still unclear. Recombinant lipocortin I inhibits eicosanoid synthesis in isolated perfused lungs from the guinea pig. Here, we report that synthetic oligopeptides corresponding to a region of high amino-acid sequence similarity between uteroglobin and lipocortin I have potent PLA2 inhibitory activity in vitro and striking anti-inflammatory effects in vivo.

Amino Acid Sequence↗
PubMed1988

Detection of a rabbit uteroglobin-like protein in human neonatal tracheobronchial washings.

Uteroglobin is a steroid hormone dependent, low molecular weight, secretory protein with many immunomodulatory properties. Immunomodulation by this protein may, at least in part, be related to its inhibitory effects on phospholipase A2 activity. Although uteroglobin is conclusively found in the rabbit, its presence in the human is controversial. Here, we present biochemical and immunological evidence for the detection of a uteroglobin-like protein in the wet epithelial living of the respiratory tract of human neonates. Because inhibition of phospholipase A2 may modulate tissue eicosanoid levels and since many eicosanoids (i.e. prostaglandins and leukotrienes etc.) are well known regulators of smooth muscle contractility, cellular migration and inflammatory processes, the discovery of this protein in the human respiratory tract may have important physiological implications.

Animals↗
PubMed1988

Inhibition of phagocyte chemotaxis by uteroglobin, an inhibitor of blastocyst rejection.

Uteroglobin, a steroid-dependent secretory protein first discovered in the rabbit uterus during early pregnancy, is a potent phospholipase A2 inhibitor. We found that uteroglobin also inhibited human and rabbit phagocyte chemotaxis in response to formyl peptide attractants in a dose-dependent manner. Half-maximal inhibition was at 1.2 microM. Uteroglobin did not compete with a formyl peptide for its receptor but inhibited internalization of radiolabeled formyl peptide. Uteroglobin appears to inhibit chemotaxis by a mechanism different from that of dansylcadaverine, a well studied inhibitor of endocytosis. Unlike dansylcadaverine, uteroglobin did not have any effect upon the synthesis of phosphatidylcholine or phosphatidylinositol. It is suggested that uteroglobin may protect trophoblastic cells from the defense system of the host not only by binding to antigenic determinants of embryonic cells but also by impairing migration of phagocytes, one of the primary components of the immune defense system. These results may explain why embryonic cells do not elicit an inflammatory response in the uterine endometrium during pregnancy.

Animals↗
PubMed1988

Sequence of centromere separation of mitotic chromosomes during human cellular aging.

The sequence of centromere separation of mitotic chromosomes derived from lymphocytes of 17 individuals of various ages was studied. A comparison of the mean CSI (centromeric separation index) values for individual chromosomes in the complement indicated a significant difference between the older and the younger subjects only with regard to the chromosome nos. 6, 11, and 19 in both sexes and the X chromosome exclusively in the female. With age, chromosome no. 6 in both males and females and the X chromosome in females showed premature centromeric separation whereas chromosome nos. 11 and 19 in both males and females displayed delayed centromeric separation. Our study, therefore, indicates that changes in the sequence of centromeric separation of certain chromosomes do occur in lymphocytes during chronological aging in humans.

Adult↗
PubMed1988

Culture media variation as related to in vitro aging of human fibroblasts: II. Effects on nucleolar number/cell, volume/nucleolus and total nucleolar volume/cell.

The relative effect of five commonly used culture media (MEM, BME, McCoy's 5A, M199 and HMEM) on the average nucleolar number/cell, the average volume/nucleolus and the total nucleolar volume/cell was examined during in vitro senescence of WI-38 human fetal fibroblasts. Statistical analyses show that cells aging in MEM show a higher number of nucleoli/cell than that of cells aging in any other medium. For cells aging in the other four media, there are no significant differences in the average number of nucleoli/cell. Linear regression analysis shows that in all cases there is a linear decrease in the average number of nucleoli/cell as a function of PDL. Statistical analyses show that the average volume/nucleolus is significantly greater for cells aging in M199 than in any other medium. Cells aging in HMEM show smaller average nucleolar volume than cells aging in M199, but display larger volumes than that of cells aged in BME, McCoy's 5A, or MEM. Cells aging in BME and McCoy's 5A media show no significant difference among each other in terms of average nucleolar volume, but a difference in this parameter is noted in cells aging in BME and MEM. A linear regression analysis shows that the average volume/nucleolus increases linearly as a function of age for cells grown in all five media. Analysis of the total nucleolar volume/cell in the five media shows that cells aging in M199 and HMEM are not significantly different from each other in terms of this variable, but show significantly larger volumes than those of cells aging in BME, McCoy's 5A and MEM. Cells aging in BME, McCoy's 5A and MEM display no significant difference with regard to this parameter. Linear regression analysis shows a positive linear relationship between the PDL and the total nucleolar volume/cell. The relative effects of all five media are not the same on the three cellular variables studied during in vitro aging of WI-38 cells. We, therefore, suggest that one should note this medium differential in order to allow meaningful comparison of results on possible changes in various morphological parameters during in vitro senescence of diploid human fibroblasts.

Cell Division↗
PubMed1988

Expression of a uteroglobin-like protein in human prostate.

Phospholipase A2 (PLA2) is a key enzyme that initiates the arachidonic acid cascade responsible for the synthesis of prostaglandins and leukotrienes, compounds well known for their inflammatory properties. Inhibition of this enzyme may modulate prostaglandin and leukotriene tissue levels. Uteroglobin is a potent PLA2 inhibitor found in rabbit uterus, prostate, seminal vesicle, and tracheobronchial tree. Tissue from ten human patients undergoing prostatectomy was examined for presence of a uteroglobin-like protein. Seven patients underwent transurethral resection and three had an open prostatectomy. Preoperative diagnosis in nine of the 10 patients was benign prostatic hypertrophy. One suspected, poorly differentiated, adenocarcinoma was confirmed and one unsuspected, well differentiated, adenocarcinoma was discovered. Specimens were submitted for Western blot, electron microscopy with immunogold staining, radioimmunoassay, and immunofluorescence. Six patients had evidence of uteroglobin-like protein, three with high levels (greater than or equal to 1000 pg./mg. protein), two with moderate levels (75 to 250 pg.), one with a low level (less than or equal to 75 pg.). Uteroglobin-like protein was present in all three patients who underwent open prostatectomy and in three of the seven patients with transurethral resections. The uteroglobin-like protein level was 2.5 to five times greater in both prostatic utricle specimens. All four assays corroborated these results. Because rabbit uteroglobin coats sperm and masks spermatic antigenicity in the rabbit female genital tract, this report of biochemical and immunological evidence for uteroglobin-like protein in the human prostate may have implications for human male fertility.

Adenocarcinoma↗
PubMed1988

Relationship between leukotriene C4 and an uteroglobin-like protein in nasal and tracheobronchial mucosa of children. Implication in acute respiratory illnesses.

Secretions from the nose and nasopharynx (NPS) are more readily accessible than tracheobronchial secretions (TBS) for clinical investigations, but it is unclear whether changes in mediator release in the nasopharynx reflect similar changes in the tracheobronchial tree. In order to clarify this question, NPS and TBS were taken from 20 children with tracheotomy and tested for the presence of leukotriene C4 (LTC4) and uteroglobin-like protein (UTG-LP). LTC4 and UTG-LP were measured both when the children were healthy and when they had clinical evidence of an acute respiratory tract illness. The mean concentration of LTC4 in NPS and TBS increased during illness although the mean concentration in NPS was significantly higher than in TBS during respiratory illness. In healthy children UTG-LP was detected only in TBS. During acute respiratory illness the concentration of UTG-LP in TBS decreased but remained significantly higher than in NPS. Data presented in this study indicate that changes in the LTC4 concentration in NPS appear to reflect changes in LTC4 concentration in TBS although the levels of LTC4 in NPS were significantly higher than in TBS. An inverse correlation between the concentrations of LTC4 and UTG-LP in NPS and TBS was demonstrated.

Acute Disease↗
PubMed1988

Partial characterization of a uteroglobin-like protein in the human uterus and its temporal relationship to prostaglandin levels in this organ.

During the past decade several corticosteroid-dependent, low mol wt proteins with phospholipase-A2 (PLA2) inhibitory activity have been described. This family of proteins is collectively known as lipocortins. Blastokinin or uteroglobin (utg), a progesterone-induced protein, first discovered in the pregnant rabbit uterus, is also a potent PLA2 inhibitor, but genetically distinct from lipocortins. Although utg has been found in rabbits, its presence in humans has not been well established. Here, we present biochemical, immunological, and immunohistological evidence for the detection of a utg-like protein in the human uterus. Since inhibition of PLA2 may modulate tissue eicosanoid levels and since rabbit utg has been reported to be a potent PLA2 inhibitor, we also studied the temporal relationship between utg and tissue prostaglandin E2 and F2 alpha levels in estrogen- and progesterone-dominated endometrial tissue. We found an inverse temporal relationship between utg-like protein and eicosanoid levels in this organ. Since some eicosanoids (e.g. prostaglandins, leukotrienes, etc.) are known to be involved in smooth muscle contractility and inflammatory processes, our findings may help to understand the pathogenesis of some human disorders in which abnormal eicosanoid production occurs.

Adult↗
PubMed1987

Inhibition of thrombin-induced platelet aggregation by uteroglobin.

Uteroglobin, a steroid-dependent, small molecular weight (15K) protein in the rabbit, inhibited thrombin-induced aggregation of both rabbit and human gel-filtered platelets (GFP). GFP aggregation by arachidonic acid was not affected by uteroglobin. There were no effects of uteroglobin on thrombin-induced clotting of plasma or purified fibrinogen, or inhibition of thrombin by antithrombin III. Additionally, preliminary results suggest that uteroglobin does not interfere with binding of thrombin to platelets. We suggest that inhibition of platelet aggregation by uteroglobin may function in preventing thrombosis and ensuring free flow of blood through the microvasculature of the uterus and the placenta and may induce some of the antimotility effects of progesterone on the uterus.

Animals↗
PubMed1987

Transketolase abnormality in cultured fibroblasts from familial chronic alcoholic men and their male offspring.

We have investigated a thiamine-dependent enzyme, transketolase, in cultured fibroblasts from 41 human subjects, including patients with alcoholism-associated Wernicke-Korsakoff syndrome (n = 3), familial chronic alcoholic males (n = 7), their sons (n = 7), nonalcoholic men (n = 7), their male offspring (n = 7), and three generations of an Amish family (n = 10) without any history of alcoholism. This study was undertaken to delineate whether transketolase abnormality (i.e., high Michaelis Menton constant (Km) for thiamine pyrophosphate), previously reported in patients with Wernicke-Korsakoff syndrome is prevalent among familial chronic alcoholic men and their sons without prior history of alcohol abuse but who are at high risk for alcoholism. Our data suggest that an inborn error (i.e., high Km of transketolase for thiamine pyrophosphate) predisposing to thiamine deficiency diseases similar to those reported in Wernicke-Korsakoff syndrome may occur in the general population. However, for some as yet unexplained reason(s) this variant seems to occur more frequently among familial chronic alcoholic men and their male offspring without any history of alcoholism. The inheritance pattern of this enzyme variant as revealed from an Amish pedigree study may be autosomal recessive as previously suggested.

Adolescent↗
PubMed1987

Uteroglobin: structure, molecular biology, and new perspectives on its function as a phospholipase A2 inhibitor.

UG or blastokinin is a low molecular weight protein which is secreted by the endometrium of the rabbit during early pregnancy. Its synthesis and secretion by the endometrium are regulated by ovarian steroids, especially P. However, the protein is also produced by tracheo-bronchial, gastrointestinal, prostatic, and seminal vesicular epithelium. In the respiratory tract, UG synthesis is under glucocorticoid control. The hormonal regulation of UG synthesis in organs other than the endometrium and tracheobronchial epithelium is poorly understood. The structure of this protein and its gene has been extensively investigated while its physiological function is still unclear. Since UG, after reduction of its two disulfide bonds, has the ability to bind P and related steroids, it has been suggested that this protein is a P carrier or a P scavenger. However, the protein does not bind glucocorticoids, estrogens, or androgens and its presence in organs other than the uterus cannot be explained on the basis of its P binding. Recent data indicate that UG has other interesting biological properties. These include antichemotactic/antiphagocytic effects on macrophages, monocytes, and neutrophils, tolerogenic effect on both blastomeres and spermatozoa against recognition by maternal lymphocytes, and its ability to inhibit thrombin-induced platelet aggregation. Moreover, UG has been shown to be a potent phospholipase A2 inhibitor. The latter property could suggest a possible mechanism of some of the observed biological effects of this protein. The structural similarities of UG with phospholipase A2 and with other PLA2 inhibitory proteins like lipocortins may suggest that the physiological function of this protein may be primarily immunomodulatory through its function as a PLA2 inhibitor. The possible occurrence of similar proteins in other species, including humans, may confirm this hypothesis. Additionally, our hypothesis may lend support to the suggestion that P may be nature's immunosuppressant during pregnancy.

Animals↗
PubMed1986

Culture media variation as related to in vitro aging of human fibroblasts: I. Effects on population doubling, nuclear volume and nuclear morphology.

The relative effect of five commonly used culture media (MEM, BME, McCoy's 5A, M199 and HMEM) on the population doubling level (PDL), nuclear volume and nuclear morphology was examined during in vitro senescence of WI-38 human fetal fibroblasts. Statistical analyses showed that cells grown in M199 had a significantly lower PDL than that of cells cultured in any other medium. The PDL in McCoy's 5A was significantly lower compared to that in BME, MEM and HMEM. Cells grown in BME, MEM and HMEM showed similar PDL. It was found that the nuclei of aged cells grown in M199 were significantly larger in volume than cells aged in any other medium. The average increases in nuclear volume of cells during aging in BME, MEM and McCoy's 5A were statistically equivalent. The increase in nuclear volume in HMEM was significantly smaller than that of cells aging in M199 and was longer than that of cells aging in BME or MEM. Linear regression analysis showed that there was a linear increase in nuclear volume as a function of PDL for cells aged in all five media. However, the rate of increase in nuclear volume with increasing PDL varied from medium to medium. There was no significant difference between media on induction of abnormal nuclear morphology as related to PDL. The relative effects of all five media were not uniform on the three cellular parameters investigated during in vitro aging of WI-38 cells. It is, therefore, suggested that one should keep this medium differential in mind to allow meaningful comparison of possible changes in various morphological parameters during in vitro senescence of diploid human fibroblasts such as WI-38.

Cell Line↗