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Biomedical subjects

A Dutt

Publications and source records attributed to A Dutt.

At least 19 recordsLinked to original sources
PubMed2002

Correlation between CT scan and automated perimetry in supratentorial tumors.

An attempt was made to correlate various types of visual field defects on automated perimetry with the findings of computed tomography in 44 patients of supratentorial tumors. All the patients above the age of 10 years were subjected to complete neurological examination including investigations like plain X-rays and CT scan, however, MRI and angiography were performed wherever indicated. Ocular examination particularly pertaining to neuro-ophthalmological profile was carried out with special emphasis on automated perimetry on Humphrey field analyser. The results indicated that automated perimetry was capable of reliably detecting and quantitating the visual field defects and thus established the location of the tumor in 72% patients when compared to CT scan. Hence, any patient with neuro-ophthalmic features should be subjected to automated perimetry for early diagnosis and probable location of intracranial space occupying lesion affecting visual pathways.

Adult↗
PubMed1995

Functional expression of the renal organic cation transporter and P-glycoprotein in Xenopus laevis oocytes.

The hypothesis that P-glycoprotein (P-gp) mediates the renal secretion of organic cations was tested by functional expression of mRNAs in the Xenopus laevis oocyte system. Efflux of 2'-deoxytubercidin (dTub), a substrate for the renal organic cation transporter (OCT) but not for P-gp, was enhanced by injection of renal mRNA but not by injection of mRNA from P-gp-overexpressing cells (MDCK cells transduced with the cDNA for human MDR1). The functional capacity of the MDCK-MDR mRNA was established by its ability to reduce the steady-state uptake of a classical P-gp substrate, vinblastine. Thus, these data indicate OCT and P-gp to be distinct entities. The Xenopus oocyte system provides a functional approach to further characterize the OCT.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

P-glycoprotein and organic cation secretion by the mammalian kidney.

On the basis of physiological localization, broad substrate specificity and energy dependence, the role of the kidney P-glycoprotein was tested in the energy-dependent renal secretion of organic cations. P-glycoprotein-enriched vesicles from Cl 1D/VCR [a multidrug-resistant (MDR) cell line] displayed enhanced transport of the MDR drug vinblastine and the organic cation cimetidine but not of the organic cation tetraethylammonium (TEA) over that shown by vesicles prepared from the drug-sensitive parental line Cl 1D. An outwardly directed proton gradient stimulated TEA and cimetidine uptake by renal brush border membrane vesicles (BBMV) but this gradient did not enhance the uptake of these organic cations into Cl 1D/VCR vesicles. Vinblastine uptake was unaffected by the proton gradient in either vesicle preparation. An outwardly directed gradient of TEA enhanced the uptake of TEA into renal BBMV but did not do so in the case of Cl 1D/VCR vesicles. These data indicate that P-glycoprotein, which is normally energized by ATP hydrolysis, is incapable of catalyzing organic cation/proton exchange or organic cation/organic cation exchange, properties of the organic cation carrier of renal proximal tubule BBMV. The MDR substrates and modulators inhibited the uptake of vinblastine and cimetidine by Cl 1D/VCR vesicles and the uptake of cimetidine and TEA by renal BBMV. Several organic cations studied inhibited TEA and cimetidine uptake by renal BBMV but did not inhibit the uptake of vinblastine and cimetidine by Cl 1D/VCR vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Enhanced transepithelial flux of cimetidine by Madin-Darby canine kidney cells overexpressing human P-glycoprotein.

Cimetidine has been used as a relatively selective inhibitor of renal organic cation secretion, analogous to the use of probenecid to inhibit organic anion secretion. Many of the substrates for the multidrug transporter P-glycoprotein, which is overexpressed in multidrug-resistant tumor cells, are organic cations. Furthermore, the protein is normally expressed on the apical membranes of proximal tubule cells, the postulated site for active organic cation secretion. To test directly whether P-glycoprotein might serve as a carrier for cimetidine, we measured cimetidine transepithelial movement across Madin-Darby canine kidney cells grown as monolayers on membrane filters. A retrovirally transduced Madin-Darby canine kidney cell line (Madin-Darby canine kidney cells transfected with the human multiple drug resistance 1 cDNA for P-glycoprotein), that expresses the human form of P-glycoprotein on its apical membrane, had an increased capacity to transport cimetidine from the basolateral to apical medium (b-->a) but not in the reverse direction (i.e., a-->b). Qualitatively similar results were observed with daunomycin, a well established substrate for P-glycoprotein. Cellular uptake and energy-dependent efflux experiments further established cimetidine to be a substrate for the human P-glycoprotein. Thus, P-glycoprotein may play a role in the renal secretion of cimetidine and perhaps other organic cations.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Effect of reserpine on the inhibition of prolactin released from different pituitary constructs in vitro by dopamine, bromocriptine and apomorphine.

Hourly release of Prolactin by pituitary constructs 1 whole pituitary (PI), adenohypophysis (P-N) and pituitary-hypothalamus co-incubate (PHC) were compared. Adenohypophysis secreted significantly more prolactin than PI and PHC, while PHC secreted significantly less than PI. Co-incubation of (P-N) with posterior pituitary reduced the elevated secretion of prolactin. Addition of dopamine (10(-7) M), bromocriptine (10(-7) M) and apomorphine (5 x 10(-8) M) to these constructs did not affect the release of prolactin from PI but inhibited the same from (P-N) and PHC. Treatment with reserpine increased serum prolactin levels but intrapituitary prolactin contents were decreased. Hourly release of prolactin from pituitary constructs derived from reserpine-treated rats was significantly reduced as compared to ascorbic acid--treated controls. Inclusion of dopamine (10(-7) M), bromocriptine (10(-7) M) and apomorphine (5 x 10(-8) M) in these constructs inhibited prolactin secretion further. In vitro addition of perphenazine stimulated the release of prolactin by PHC but was without any effect on PI and (P-N). The data are interpreted to suggest that dopamine in posterior pituitary may be an important determinant of hypothalamic modulation of prolactin secretion.

Animals↗
PubMed1992

Tidal breath flow-volume curves in obstructive sleep apnea.

Because of the gravitational position during sleep and the associated relaxed state, we hypothesized that passive expiration in the supine position might reflect upper airway pathophysiology in obstructive sleep apnea (OSA). We prospectively enrolled and tested 92 subjects with several clinical conditions. Maximal comfort and relaxation during expiration was achieved by connecting subjects to a ventilator via a mouthpiece. An initial respiratory rate of 16 breaths/min and tidal volume of 10 ml/kg were selected. Fine adjustments were then made to achieve maximal subject relaxation. Using this method, we obtained reproducible tidal breath flow-volume curves (TBFVC). Testing was performed in both sitting and supine positions. Standard pulmonary function tests, including spirometry and lung volume measurements, were also obtained in both sitting and supine positions. Of 86 patients who could be evaluated, 12 (60%) of 20 subjects with documented OSA (respiratory disturbance index: mean, 64.8; range, 10 to 120.5) demonstrated a positional change in the terminal portion of the TBFVC; 10 (32%) of 31 with a history of snoring also tested positive, but only three (9%) of 35 subjects with no OSA, by polysomnography (n = 8) or questionnaire (n = 27), demonstrated such a positional change. This positional change in TBFVC, which was significantly more frequent in subjects with OSA, could not be attributed to any measurable pulmonary function abnormality or body mass index. We believe this positional change in TBFVC reflects upper airway functional narrowing induced by assumption of supine position and decreasing airflow rates.

Female↗
PubMed1992

Postnatal development of organic cation transport and mdr gene expression in mouse kidney.

The apical surface of the proximal tubular epithelium is the site of both P-glycoprotein localization and postulated active secretion of organic cations in the mammalian kidney. P-glycoprotein has been shown to act as a pleiotropic drug efflux pump across the cell membrane of tumor cells expressing the multidrug resistance phenotype, whereas the renal organic anion and organic cation secretory systems serve the function of pleiotropic drug transport across the proximal tubule epithelium. Because most known substrates for P-glycoprotein are organic cations, we tested the hypothesis that the physiological function of this protein in the kidney is to mediate renal organic cation secretion. In one approach, we compared the postnatal development of organic cation transport with that of kidney mdr gene expression. Cimetidine-sensitive uptake of classical substrates for renal secretion (N-methyl nicotinamide and tetraethylammonium) into kidney slices developed gradually in neonate mice, reaching adult capacity in 4 to 6 weeks. P-glycoprotein and its mRNA, as estimated by immunohistochemical methods and RNAse protection analysis, were undetectable at birth and were expressed abruptly at the adult level between 2 and 3 weeks of age. In another approach, classical inhibitors of renal organic cation secretion (cimetidine and cyanine 863) failed to reverse resistance to adriamycin in Chinese hamster ovary and P388 cell lines, which possess the phenotypic traits of multidrug resistance. These results suggest that the cimetidine-sensitive component of organic cation secretion is mediated by a protein other than the P-glycoprotein in the mammalian kidney.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Diurnal variations and temporal coupling of bioactive and immunoactive luteinizing hormone, prolactin, testosterone and 17-beta-estradiol in adult men.

Diurnal variations and temporal coupling in the circulating levels of immunoactive and bioactive luteinizing hormone (LH) and prolactin (PRL), testosterone (T) and 17-beta-estradiol (E2) in plasma of 6 healthy men (mean age 33 years) were studied. Each hormonal profile was analyzed for circadian amplitude, acrophase and nadir. Acrophases for immunoactive LH and T were coincident and ranged between clock hours 1 and 5. Acrophase for bioactive LH ranged between 9 and 12 h and was coincident with nadir for T. Acrophase for E2 ranged between 15 and 18 h and was coincident with nadir for immunoactive LH (15-17 h). Acrophase for bioactive PRL and immunoactive PRL ranged between 20-23 and 23-4 h, respectively. The circadian amplitude for T showed a negative correlation coefficient with circadian amplitude of bioactive LH (alpha = -0.86) and positive correlation coefficient with circadian amplitude of immunoactive LH (alpha = 0.94). It is inferred that immunoactive LH may be a sensor of T concentration while bioactive LH may be actually involved in the feedback regulation of T secretion. It is suggested that PRL may have a key role in the regulation of LH secretion.

Adult↗
PubMed1991

Epidemiology of extrapulmonary tuberculosis. A comparative analysis with pre-AIDS era.

To study the changes in the epidemiology of extrapulmonary tuberculosis in Tennessee, we compared the 454 cases of extrapulmonary tuberculosis reported between 1977 and 1981 with 356 cases encountered between 1982 and 1986. The data were analyzed by age, sex, race and site of the disease which were compared with the national statistics during the periods. We observed that 11.3 percent of the total TB cases were extrapulmonary. Unlike national statistics, the proportion of extrapulmonary tuberculosis had remained unchanged between the two study periods. Except for a significant decline (p less than 0.001) in genitourinary tuberculosis, the incidence of other extrapulmonary TB had remained the same. The higher incidences of lymphatic, miliary, and meningeal TB were noted in nonwhites, particularly in the younger population, during both study periods. While the national trend showed a steady increase in the percentage of extrapulmonary TB cases, there was no change in Tennessee. The reason for a continued decline of GU TB remains unclear. Although AIDS may have contributed toward the increase nationally, fewer cases of AIDS in the state have not influenced the proportion of extrapulmonary TB. Awareness of such regional differences in the epidemiology of TB, and the impact of HIV infection, will be very useful to physicians and other health care providers involved in the diagnosis, treatment, and prevention of tuberculosis.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Lactosaminoglycan assembly, cell surface expression, and release by mouse uterine epithelial cells.

The kinetics of assembly, cell surface expression, secretion, and degradation of the major lactosaminoglycan (LAG)-bearing glycoproteins in mouse uterine epithelial cells have been studied. LAGs have been shown previously to be synthesized preferentially by these cells in the uterus and are expressed at the cell surface, where they participate in cell adhesion processes (Dutt, A., Tang., J.-P., and Carson, D. D. (1987) Dev. Biol. 119, 27-37). We utilized selection on pokeweed mitogen-Sepharose, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and subsequent electroelution to isolate the major LAG-bearing glycoproteins. The intact LAG-bearing glycoproteins exhibited very high apparent Mr (greater than 500,000) both by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and molecular exclusion chromatography under dissociative conditions. The subset of LAGs at the cell surface exhibited a half-life of approximately 11 h, whereas total cell-associated LAGs had a half-life of 6 +/- 1 h. Pulse-chase experiments indicated that the transit time of LAG core proteins from the rough endoplasmic reticulum to the site of LAG addition in the Golgi was 30-45 min. LAG glycoprotein transit from the Golgi to the cell surface required at least an additional 30-45 min. The major metabolic fate of the cell-associated LAGs was secretion to the medium with no evidence of lysosomal degradation. Some (30%) of the LAGs appeared to be released to the medium via the action of cell surface proteases. Epithelial cell surfaces bound fluoresceinated pokeweed mitogen, indicating the constitutive presence of LAG-bearing molecules at the cell surface; pokeweed mitogen binding to the cell surface was completely blocked by 10 mM chitotriose. These observations provide the first comprehensive description of the intracellular transport and metabolism of this interesting class of glycoproteins of the uterine epithelial cell surface.

Amino Sugars↗
PubMed1988

Estrogen preferentially stimulates lactosaminoglycan-containing oligosaccharide synthesis in mouse uteri.

The effects of steroid hormones on the synthesis of lactosaminoglycan (LAG)-containing oligosaccharides by mouse uteri are reported. The uterine LAG-containing oligosaccharides were degraded partially by Pseudomonas endo-beta-galactosidase, releasing an oligosaccharide of the apparent structure: Gal beta----N-acetylglucosaminyl(----N-acetylgalactosaminyl)beta 1,3----galactose. A larger fraction of the LAG-containing oligosaccharides bound to pokeweed mitogen than to Datura stramonium lectin, suggesting the presence of highly branched structures. LAG-containing oligosaccharides were resistant to sequential digestion with Pronase, nitrous acid, hyaluronidase, and chondroitinase ABC. These polysaccharides exhibited a Gal:GlcNAc:GalNAc ratio of approximately 1.0:1.0:0.3 and were not fucosylated. The ion-exchange behavior of the LAG-containing oligosaccharides before and after mild acid hydrolysis indicated the presence of sialic acid residues. The LAG-containing glycopeptides were highly resistant to beta-elimination but were released quantitatively by hydrazinolysis, demonstrating an N-linkage to protein. Binding to pokeweed mitogen was markedly enhanced following release of these oligosaccharides from peptides by hydrazinolysis, suggesting that peptide-bound oligosaccharides were partially inaccessible to the lectin. Molecular exclusion chromatography of the oligosaccharides released by hydrazinolysis revealed a broad distribution ranging from Mr 4,000 to 15,000 with a median Mr of approximately 8,000. We extended the above observations by determining how the steroid hormones 17-beta-estradiol (E2) and progesterone affected synthesis of the LAG-containing oligosaccharides in ovariectomized mice. Generally, E2 and a number of E2 agonists stimulated glycoconjugate synthesis; however, chronic E2 treatment or combined treatment with E2 plus progesterone caused the synthesis of most glycosaminoglycans to return to basal levels. In contrast, E2 either alone or in combination with progesterone stimulated synthesis of LAG-containing oligosaccharides in preference not only to glycosaminoglycans but also to other classes of N-linked oligosaccharides. This effect was apparent during both priming and nidatory E2 treatments. Collectively, these data provide the first demonstration of LAG-containing oligosaccharides in uteri and for the hormonally regulated synthesis of lactosaminoglycans. In addition, this is the first demonstration of the ability of steroid hormones to induce the synthesis of certain types of N-linked oligosaccharides in preference to others in the same tissue.

Amino Sugars↗
PubMed1987

Involvement of prostaglandin A1 in interrupting early pregnancy in Syrian golden hamsters.

The effects of a single administration of authentic prostaglandin A1 intravaginally in early pregnant hamsters were investigated. A single dose of 1 mcg/animal given on day 4 of pregnancy inhibited the appearance of embryonic swellings when observed on day 8 of pregnancy. A significant fall (p less than 0.01) in FSH with a rise (p less than 0.03) in prolactin concentration in the serum and no change in LH levels were observed. The pituitary content of prolactin showed a significant decrease (p less than 0.0006) with no change in FSH and LH contents. Progesterone concentration in the serum was markedly reduced (p less than 0.002), along with that of the ovaries (p less than 0.01). The decline in progesterone concentration coincided with the absence of corpora lutea and the embryos. However, no change in ovarian weights was observed. These results indicate the contragestive potential of prostaglandin A1. It appears to act as a luteolytic agent by disrupting the luteotropic complex (FSH:prolactin ratio).

Animals↗
PubMed1987

Glycoconjugate synthesis during early pregnancy: hyaluronate synthesis and function.

The synthesis of various glycoconjugate classes by mouse uteri during the pre- and peri-implantation period has been examined using [3H]glucosamine as a metabolic precursor. A unique and dramatic (five- to sixfold) increase was observed in the synthesis of hyaluronate on the day upon which embryo implantation normally occurs. Mated, but nonpregnant mice did not display increased hyaluronate biosynthesis. In contrast to hyaluronate, the synthesis of most other types of glycoconjugates remained fairly constant during the first 5 days of pregnancy. Low (1500-5000)-molecular-weight N-linked oligosaccharides constituted the major class of oligosaccharides synthesized under all conditions. High (greater than 10,000)-molecular-weight glycoconjugates constituted the second most abundant class of glycoconjugates synthesized (20-30%). Most (85%) of the newly synthesized hyaluronate was associated with the nonepithelial cell types of the uterus. Experiments using ovariectomized mice receiving steroid hormones demonstrated that uterine hyaluronate synthesis was induced preferentially by an artificial decidual stimulus and implicated stromal cells as the site of hyaluronate synthesis. In addition, it was demonstrated that tissue culture plates coated with hyaluronate, but not other polysaccharides, support attachment and spreading of a large fraction (60 to 70%) of embryos cultured in serum-free medium. Collectively, these studies indicate that increased hyaluronate biosynthesis accompanies decidual responses in the endometrium and may promote embryo implantation following initial penetration of the uterine epithelium.

Animals↗
PubMed1987

Lactosaminoglycans are involved in uterine epithelial cell adhesion in vitro.

The cell type specificity of glycoconjugate synthesis between the epithelial and stromal cells of the uterus is described. Lactosaminoglycans (LAGs) constituted a major fraction of the cell-associated glycoconjugates synthesized by epithelial, but not stromal, cells. Furthermore, LAGs comprised the bulk (greater than 90%) of glycoconjugates that could be released from epithelial cell surfaces by proteases. Several lines of evidence indicate that the epithelial cell-specific lactosaminoglycans appear to interact directly with a cell surface galactosyltransferase (GalTase). This includes the observation that agents that perturb galactosyltransferase function also interrupt epithelial cell adhesion and cause LAG release from the cell layer. In addition, LAGs are galactosylated when UDP-[3H]galactose is added to intact epithelial cell layers. Interference with cell surface GalTase activity with alpha-lactalbumin or UDP-galactose, but not other agents, specifically interrupted epithelial cell adhesion; however, the same agents had absolutely no effect on stromal cells. Collectively, these studies describe the novel occurrence of lactosaminoglycans on cell surfaces in an adult tissue other than hematopoietic cells and provide evidence for cell type-specific involvement of lactosaminoglycans in uterine cell adhesion processes.

Amino Sugars↗
PubMed1987

Age-related release of prolactin by the pituitary and the pituitary-hypothalamic complex in vitro: an attempt to describe the development of the hypothalamic prolactin-inhibiting and -releasing activities in male rats.

We have recently demonstrated that the pituitary hypothalamic complex (PHC) is a good model for studying interactions between the hypothalamus and pituitary in vitro. The amount of prolactin secreted by the PHC is an index of prolactin secreted by the pituitary in the presence of hypothalamic control, while the amount released by the whole pituitary alone is an index of prolactin secreted in the absence of hypothalamic control. The amount of prolactin secreted by the PHC has been regarded as an index of hypothalamic prolactin-releasing activity (HPRA), while the difference in the amounts of prolactin secreted by the whole pituitary and the PHC is the hypothalamic prolactin-inhibiting activity (HPIA). Attempts were made to correlate HPRA and HPIA to the development of serum concentrations of prolactin from days 7 to 77 in male rats. The HPRA increased steadily from days 7 to 56, decreased significantly on day 63 and thereafter remained unchanged until day 77. The HPIA was low on days 7 and 14 and increased steadily up to day 49, with no further significant variations. The developmental patterns of HPRA and HPIA were comparable up to day 49. Serum concentrations of prolactin increased significantly until day 28 and remained fairly constant until day 49. The weight of the pituitary gland increased from 1.0 +/- 0.03 mg (mean +/- S.E.M.) on day 7 to 7.76 +/- 0.32 mg on day 63 and remained unchanged thereafter. The weight of the hypothalamic islet was 31.5 +/- 2.88 mg on day 7, 34.83 +/- 1.45 mg on day 14 and 50.4 +/- 4.01 mg on day 21. After day 21 the weights of the hypothalamic islets were not significantly altered, except on day 49. It was concluded that serum concentrations of prolactin are regulated by interaction or competition between HPRA and HPIA at the level of the pituitary.

Aging↗
PubMed1986

The choice of a model for studying the hypothalamus-pituitary interactions in vitro.

Comparative studies on the release of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (Prl) by the whole pituitary, pituitary plus hypothalamus and pituitary-hypothalamus complex (PHC) were undertaken to choose an appropriate model for studying the hypothalamus-pituitary interactions in vitro and to relate the importance of the intact neural connections between pituitary and hypothalamus on hypothalamus-pituitary interactions. Also the effect of including dopamine (DA) at 1 X 10(-7) mol/1 in these different in vitro systems on the release of LH, FSH and Prl was investigated. The pituitary released increasing amounts of LH and FSH at 2, 4 and 6 h but the amount of Prl released remained unchanged. The rates of release of LH, FSH and Prl by the pituitary were different and were characteristic of each hormone. Co-incubation of pituitary with hypothalamus stimulated the release of LH and FSH but inhibited the release of Prl. Pituitary-hypothalamus complex behaved almost identical to behaved almost identical to pituitary plus hypothalamus system. Inclusion of 1 X 10(-7) M DA in the incubation medium stimulated the release of LH (80%) but inhibited the release of Prl (71%) by PHC. FSH was unaffected. DA had no significant effect on the release of LH, FSH and Prl by pituitary and pituitary plus hypothalamus systems. It is suggested that PHC is the system of choice for studying hypothalamus-pituitary interactions in vitro.

Animals↗