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A Chaudhry

Publications and source records attributed to A Chaudhry.

At least 55 records · Page 3Linked to original sources
PubMed1994

Different splice variants of CD44 are expressed in gastrinomas but not in other subtypes of endocrine pancreatic tumors.

Endocrine pancreatic tumors are neuroendocrine neoplasms with malignant potential and give rise to varied clinical syndromes due to excessive secretion of multiple hormones. In this study 22 endocrine pancreatic tumors and 11 carcinoid tumors were examined for the expression of CD44 using a monoclonal antibody. CD44 gene activity of 11 endocrine pancreatic tumor tissues and five carcinoid tumor tissues was also studied by amplifying messenger RNA with the polymerase chain reaction followed by electrophoresis and blot hybridization. Strong immunoreactivity was detected on all gastrinomas examined (P < 0.001), and in two non-functioning endocrine pancreatic tumors. Such immunoreactivity was not observed in other subtypes of endocrine pancreatic tumors. In the normal human pancreas, the acinar portion and ductal epithelial cells stained strongly positive but pancreatic islet cells did not show any significant immunostaining. Furthermore, in endocrine pancreatic tumors with metastatic disease, CD44-positive tumors had a tendency to metastasize to lymph nodes (P = 0.005), as compared with CD44-negative tumors which were locally invasive or metastasized to the liver. Although, in this limited material and short follow-up, we were not able to show any statistical significance, patients with CD44-negative endocrine pancreatic tumors had prolonged survival time compared with patients with CD44-positive tumors (73% versus 59% at 5 years; P = 0.7). Of 10 carcinoid tumors examined, all three foregut carcinoids and one midgut carcinoid stained strongly positive, whereas all other midgut carcinoids were negative. Analysis of CD44 splice variants showed that in all five gastrinomas there was overproduction of alternatively spliced larger molecular variants as compared with other types of endocrine pancreatic tumors and carcinoid tumors. The band pattern from one case of carcinoid tumor with a fulminant clinical course was similar to that of gastrinomas, whereas other carcinoid tumors expressed the epithelial form of CD44. The earlier identified splice variants which confer metastatic behavior on a pancreatic tumor cell line were not expressed in neuroendocrine tumors. Our data indicate that CD44 expression in endocrine pancreatic tumors correlates with the ability to give rise to lymph node metastases and may play a vital role in determining the fate of metastasizing cells. Moreover, because gastrin is not detectable in the normal human pancreas, the pancreatic ductal cell positivity for CD44 strengthened the ductal origin concept of gastrinomas. The band pattern of CD44 splice variants suggests that the previously described splice variants conferring metastatic behavior do not accompany metastatic activity of neuroendocrine tumors.

Adult↗
PubMed1994

Differential interaction of beta 1- and beta 3-adrenergic receptors with Gi in rat adipocytes.

The interaction of beta 1- and beta 3-adrenergic receptors and G(i) proteins was examined in rat adipocytes. In intact adipocytes, cyclic AMP accumulation stimulated by the beta 3-selective agonist, BRL 37344 (BRL), was potentiated by pertussis toxin (PTX), as was the beta 1-sensitive component of isoproterenol (ISO)-stimulated cyclic AMP accumulation. These data suggest that beta 1 and beta 3-receptors interact with both Gs and G(i) in intact adipocytes. Further analysis of the activation of adenylyl cyclase by the beta-receptor subtypes was performed in adipocyte membranes in which the activity of G(i) was manipulated by both GTP and PTX. Unlike cyclic AMP accumulation in cells, the activation of membrane adenylyl cyclase by ISO could be clearly resolved into components mediated by beta 1-(high affinity) or beta 3-(low affinity) receptors. The beta 3-receptor-mediated activity was dramatically reduced at 0.1 mM GTP compared to 0.1 microM GTP, but the activity mediated by beta 3-receptors was significantly reduced at concentrations of GTP in which G(i) proteins are active. Adenylyl cyclase activity stimulated by BRL was also inhibited at high concentrations of GTP. PTX abolished the inhibition of beta 3-receptor-stimulated activity by high GTP concentrations. This is the first study to indicate that G(i) proteins can limit beta 3- but not beta 1-stimulated adenylyl cyclase activity and are consistent with the hypothesis that beta 3-receptors interact with both Gs and G(i), whereas beta 1-receptors couple predominantly to Gs.

Adenylate Cyclase Toxin↗
PubMed1994

Influence of cell type upon the desensitization of the beta 3-adrenergic receptor.

Previous studies have suggested that the beta 3 receptor fails to become desensitized following acute agonist exposure. We have determined whether this resistance to desensitization is an intrinsic property of the human beta 3 receptor by examining beta 3 receptor-stimulated adenylyl cyclase activity in several cell types. Prior exposure to ISO significantly decreased beta 3 receptor-stimulated adenylyl cyclase activity in SK-N-MC human neuroepithelioma cells, which natively express the beta 3 receptor. ISO pretreatment significantly desensitized the recombinant beta 3 receptor when stably expressed in 293 cells, but not when the receptor was expressed in Chinese hamster ovary cells. Mutant receptors lacking the second exon of the human beta 3 receptor also underwent agonist-induced desensitization when expressed in 293 cells. Additionally, the rat beta 3 receptor, which fails to desensitize in rat adipocytes, underwent agonist-induced desensitization when expressed in 293 cells. Pretreatment with CGP 12177A, a beta 3-selective agonist, also reduced beta 3-stimulated adenylyl cyclase activity in transfected 293 cells. In contrast, 8-Br-Cyc AMP did not desensitize the beta 3 receptor. Concanavalin A, an inhibitor of receptor sequestration failed to prevent ISO-induced desensitization of the beta 3 receptor. Furthermore, radioligand binding studies showed that ISO pretreatment did not cause a loss of beta 3 receptors from 293 cell membranes. The results of the present study indicate that beta 3 receptor desensitization is dependent upon the cellular background in which this receptor is expressed. Furthermore, the mechanism responsible for beta 3 receptor desensitization does not appear to involve sequestration, cyclic AMP-dependent phosphorylation or down-regulation of the receptor.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1993

Occurrence of pyuria and bacteriuria in asymptomatic hemodialysis patients.

Patients with end-stage renal disease on hemodialysis have documented defects in their immune responses, and infections contribute significantly to their morbidity and mortality. This study prospectively detected and quantitated leukocyturia and bacteriuria in asymptomatic hemodialysis patients. Thirty-one percent of asymptomatic hemodialysis patients had significant pyuria (> 10 white blood cells per high-power field) and 25% had bacteriuria of pathologic dimensions, (> 1 x 10(5)/mL of a single microorganism). Pyuria was a good marker for significant bacteriuria in these patients. These results demonstrate that the urinary tract, even in ESRD patients on hemodialysis, may represent a significant reservoir for infection.

Bacteriuria↗
PubMed1993

Expression of growth factor peptides and their receptors in neuroendocrine tumors of the digestive system.

Neuroendocrine tumors of the digestive system are slow growing neoplasms which often present with pronounced fibrosis around tumor cells and in the peritoneal cavity. In this report 30 midgut carcinoids and endocrine pancreatic tumors were examined for the expression of peptide growth factors and their receptors, both by immunohistochemistry and in situ hybridization. Our data indicate that multiple peptide growth factors, PDGF, TGF-beta, and bFGF are expressed by these tumors. PDGF was expressed on tumor cells and stroma in 70% of tissues examined. PDGF alpha-receptor was seen on clusters of tumor cells and occasionally on adjacent stroma, whereas PDGF beta-receptor was seen only in the stroma. Our data suggest that PDGF may be involved in the autocrine stimulation of tumor cells and stimulation of stromal cell growth through paracrine and possibly autocrine mechanism. In addition, tumor tissues express all three isoforms of TGF-beta in more than half of the tissues examined. Tumor cells produce small latent complexes causing an escape from potent inhibitory effect of TGF-beta and stimulation of stromal cell growth and matrix deposition through paracrine mechanism. bFGF, a potent stimulant of endothelial cell growth, was expressed by all tumor tissues examined. Our data suggest that multiple peptide growth factors may have an important role in tumor progression and desmoplastic reaction accompanying these tumors.

Adenoma, Islet Cell↗
PubMed1993

Characterization of the human beta 3-adrenergic receptor gene.

Comparison of the rodent and human beta 3-adrenergic receptor cDNAs with the respective genomic sequences has revealed unexpectedly that these genes contain two protein-coding exons. The rat gene was cloned recently and was found to contain three exons and two introns. In the present report, the human beta 3 receptor gene was characterized and was found to consist of two exons and a single intron. Sequence analysis of the human beta 3 receptor gene identified regions in the intron that were homologous to the second exon and second intron of the rat gene. It appears that both species utilize homologous 5' donor sites in the first intron and 3' acceptor sites of the final exon. However, splicing signals within the human intron that are homologous to the second exon of the rat gene are not used. Nuclease protection assays of tissue RNA and polymerase chain reaction-amplified cDNA demonstrated conclusively that beta 3 receptor mRNA, containing two protein-coding exons, is expressed in human adipose and intestinal tissues. The pharmacological properties of the full length human beta 3 receptor were determined for the first time in Chinese hamster ovary cells, where catecholamine agonists activated adenylyl cyclase with low potency. The beta 3 receptor agonists CGP 12177 and BRL 37344 also activated adenylyl cyclase. CGP 12177 was 10-15 times more potent than either isoproterenol or BRL 37344 in stimulating adenylyl cyclase activity. These pharmacological properties differed somewhat from those reported previously for Chinese hamster ovary cells expressing the truncated receptor. However, direct comparison indicates that it is unlikely that the amino acid sequence derived from the second exon can account for these differences.

Adenylyl Cyclases↗
PubMed1992

Expression of platelet-derived growth factor and its receptors in neuroendocrine tumors of the digestive system.

Carcinoid tumors are slowly growing neuroendocrine neoplasms which often present pronounced fibrosis around the tumor cells. We have previously shown by immunohistochemistry that carcinoid tumors express platelet-derived growth factor (PDGF) beta-receptors on surrounding stromal cells. In this report, 22 midgut carcinoids and 5 endocrine pancreatic tumors were examined for the presence of PDGF with a monoclonal antibody raised against a peptide corresponding to a part of the B-chain of PDGF which reacts strongly with the B-chain and weakly with the A-chain. They were also examined for PDGF alpha-receptors with an affinity-purified polyclonal peptide antibody and for PDGF beta-receptor with the monoclonal antibody PDGFR-B2. PDGF was expressed on tumor cells and on adjacent stroma. PDGF alpha-receptor was seen on clusters of tumor cells and occasionally on adjacent stroma, whereas beta-receptors were seen only in the stroma. Tissue sections from some of these midgut carcinoids were also investigated by in situ hybridization for mRNA of PDGF A- and B-chains as well as alpha- and beta-receptors. By in situ hybridization, abundant expression of mRNA for PDGF beta-receptor and PDGF A-chain was observed in stromal cells adjacent to carcinoid tumor cell clusters, but the mRNA expression in the tumor cells themselves was at a low level. A few clustered tumor cells and stromal cells expressed mRNA for the PDGF alpha-receptor, thus consolidating the immunohistochemical findings. mRNA for the PDGF B-chain was detected in both tumor cells and stroma, but only at low levels. Our data suggest that PDGF is involved in the growth stimulation of the carcinoid tumor cells in an autocrine fashion and in the stimulation of stromal cell growth through paracrine and possibly autocrine mechanisms. Moreover, remarkably strong immunostaining of PDGF and the PDGF alpha-receptor was seen on peripheral nerve fibers.

Adult↗
PubMed1992

Adrenergic regulation of neonatal brown fat adenylyl cyclase and Gs alpha activity.

Norepinephrine (NE)-stimulated adenylyl cyclase (AC) activity increases during the perinatal period in rat brown adipose tissue (BAT), and this increase is associated with changes in the activities of both the catalytic subunit (C) and Gs alpha, the GTP-binding protein that mediates activation of C. The present study examined the role of the sympathetic nervous system in the postnatal sensitization of AC. The sympathetic innervation of BAT increased 7- to 13-fold after birth, and this increase was temporally correlated with the postnatal enhancement of AC responsiveness. 6-hydroxydopamine (6-HDA) treatment of neonates reduced tyrosine hydroxylase levels by greater than 90%. This treatment greatly reduced the perinatal increase in NE- and NaF-stimulated AC and completely abolished the increase in forskolin-Mn(2+)-stimulated activity. However, sympathectomy did not alter the postnatal increase in Gs alpha-specific activity and did not prevent the postnatal reduction in Gs alpha levels. These results demonstrate that the sympathetic innervation of BAT develops fully after birth and is essential for the postnatal increase in the activity of C but not of Gs alpha.

Adenylyl Cyclases↗
PubMed1992

A study of biological behavior based on the expression of a proliferating antigen in neuroendocrine tumors of the digestive system.

The expression of a proliferating antigen by Ki-67 immunohistochemistry was evaluated in 32 gastrointestinal carcinoids and in 5 pancreatic islet cell tumors. In the tissue sections the number of labelled nuclei was calculated per tumor area. The tumors were classified as low proliferating (less than 0.3 labelled cells/mm2), medium proliferating (0.3-1 labelled cells/mm2), and high proliferating (greater than 1 labelled cell/mm2). In 26 tumors obtained from patients receiving antitumor therapy (alpha-interferon) the proliferative activity was decreased. In treated midgut carcinoids the proliferative activity in metastatic tissue was significantly reduced (p less than 0.05). Though not statistically significant, primary midgut carcinoids collected from untreated patients displayed a lower proliferative activity than liver metastases. A survival analysis revealed that patients with tumors displaying low proliferative activity had a better survival than those with high proliferative activity (p less than 0.05). Single cell cytofluorometric DNA analyses showed regular diploid stem cell lines in the majority of tumors from untreated patients (9/11 cases). No correlation was found between the calculated proliferative activity and the DNA profile. The obtained results indicate that the expression of a proliferation antigen by Ki-67 immunohistochemistry can be used to evaluate the biological behavior of neuroendocrine tumors of the digestive system and predict survival.

Adenoma, Islet Cell↗
PubMed1992

Perinatal changes in the coupling of beta 1- and beta 3 adrenergic receptors to brown fat adenylyl cyclase.

The stimulation of adenylyl cyclase by catecholamines in neonatal brown adipose tissue (BAT) is markedly biphasic, suggesting the existence of receptors that have both high and low affinities for catecholamines. The identities of these receptors were examined by comparing responses in neonatal BAT membranes to those of Chinese hamster ovary cells which had been transfected to express the cloned rat beta 1 and beta 3 receptors. The results from these experiments indicate that high-affinity stimulation of adenylyl cyclase by catecholamines in BAT is mediated by beta 1 receptors, as evidenced by the potencies of norepinephrine and isoproterenol at this receptor and the potent blockade of the receptor by alprenolol. The low-affinity catecholamine receptor appears to be the beta 3 receptor, as indicated by the low potency of catecholamine agonists and the inability of low concentrations of alprenolol to block this activity. Furthermore, this receptor, like the cloned rat beta 3 receptor, was antagonized by (-)-4-(3-t-butylamino-2-hydroxypropoxy)benzimidazol-2-one (CGP 12177) and was stimulated by (R',R')-4-(2-[(2[(3-chlorophenyl)-2- hydroxyethyl]amino)propyl]phenyl)phenoxyacetic acid (BRL 37344). These results indicate that both beta 1 and beta 3 receptors couple to adenylyl cyclase in BAT and that activation of adenylyl cyclase in neonatal BAT is mediated primarily by beta 3 receptors. Beta 3 receptors were also clearly detected in weanling BAT with the beta 3-selective agonist BRL 37344. However, when catecholamines were used to stimulate activity, the activation of adenylyl cyclase by beta 1 receptors, which occurred at low concentrations of catecholamines, obscured the activation of adenylyl cyclase by beta 3 receptors, which occurred only at high concentrations.

Adenylyl Cyclases↗
PubMed1991

Subcellular distribution of adenylyl cyclase and Gs alpha in rat brown adipose tissue.

The subcellular distribution of Gs alpha (the alpha-subunit of guanine nucleotide-binding stimulatory protein of adenylyl cyclase) was examined in interscapular brown adipose tissue (IBAT) to determine (1) if Gs alpha is completely colocalized with adenylyl cyclase in the plasma membrane, and (2) whether cold exposure, which increases adenylyl cyclase activity, changes the subcellular distribution of Gs alpha. Subcellular fractions were prepared from IBAT by differential centrifugation and analyzed for Gs alpha by immunoblotting. Adenylyl cyclase activity and Gs alpha were detected in all the subcellular fractions except the cytosol. The plasma membrane fraction showed the greatest enrichment of adenylyl cyclase and Gs alpha. However, the enrichment of adenylyl cyclase in the plasma membrane fraction was greater than that for Gs alpha, which was also associated to a large degree with the mitochondrial fraction. Thus, compared with the mitochondrial fraction, both 5' nucleotidase and adenylyl cyclase were enriched by over 200% in the plasma membrane fraction, but Gs alpha was enriched by only 50%. Exposure of rats to 4 degrees C for 3 days increased fluoride-stimulated adenylyl cyclase activity, but did not increase the amount of immunoreactive Gs alpha in any of the subcellular fractions examined. The above results demonstrate that not all Gs alpha in IBAT is colocalized with adenylyl cyclase in the plasma membrane. The finding that cold exposure did not change the subcellular distribution of Gs alpha indicates that the cold-induced increase in adenylyl cyclase activity is not due to translocation of Gs alpha from subcellular compartments to the plasma membrane.

5'-Nucleotidase↗
PubMed1991

Characterization of circulating lymphocytes by monoclonal antibodies in childhood and adult leprosy.

Peripheral blood lymphocyte assays using monoclonal antibodies were done in 66 patients with leprosy, consisting of 25 children and 41 adults. The results were statistically analyzed for correlations, if any, among the different age groups and matched controls. The results, however, failed to show any significant correlation, nor was it possible to draw any conclusion as to why the disease spectrum in children tends to be incomplete (ie, there is a low incidence of the highly bacilliferous form of disease expression).

Adolescent↗
PubMed1991

Developmental changes in adenylyl cyclase and GTP binding proteins in brown fat.

During the perinatal period, norepinephrine (NE)-stimulated adenylyl cyclase activity increased in interscapular brown adipose tissue (IBAT) membranes and then declined to adult levels by 23 days postpartum. The developmental patterns of NE- and NaF-stimulated activities were identical, indicating that the developmental increase in transmitter-stimulated activity resulted from the increased interaction of alpha-subunit of guanine nucleotide-binding stimulatory protein of adenylyl cyclase (Gs alpha) with the catalytic subunit (C). This increased Gs alpha-C interaction was the result of an increase in Gs alpha specific activity, as assessed in cyc- reconstitution assays, as well as an increased C activity, as assessed by forskolin-Mn(2+)-stimulated adenylyl cyclase activity. Although adenylyl cyclase activity increased during the perinatal period, total Gs alpha levels significantly declined because of the loss of the small-molecular-mass form of Gs alpha. Thus the ratio of large to small form of Gs alpha increased threefold and might have contributed to the perinatal increase in activity. Gi alpha-like proteins, as assessed by pertussis toxin-catalyzed [32P]ADP ribosylation, declined dramatically after birth. However, this loss of Gi alpha did not contribute to developmental changes in adenylyl cyclase activity because pertussis toxin treatment failed to alter NE-stimulated activity. In contrast to G alpha subunits, there were no changes in membrane levels of G beta subunits.

Adenylyl Cyclases↗
PubMed1991

Sustained supraventricular tachyarrhythmias following coronary artery bypass surgery comparing mammary versus saphenous vein grafts.

This retrospective study was designed to determine the incidence of sustained supraventricular tachyarrhythmias (SVTs) in patients undergoing coronary artery bypass grafting (CABG) with internal mammary artery (IMA) grafts, Group A, compared with those with saphenous vein grafts (SVG), Group B. Among 569 consecutive patients who underwent CABG surgery in the same institution, a total of 80 cases from Group A and 80 cases from Group B were selected for this study after application of exclusion criteria. Excluded from this study were the following: patients with preexisting or prior history of SVTs, significant left ventricular dysfunction (ejection fraction less than 40%), postoperative myocardial infarction, drug toxicity or electrolyte imbalance, and advanced chronic obstructive lung disease. Group A consisted of 63 men and 17 women and Group B consisted of 52 men and 28 women. All patients were monitored either in ICU or by telemetry for a period of three to six days after surgery and all had a predischarge 12-lead electrocardiogram. Both groups were fairly comparable in most of their clinical profile and number of grafts. The incidence of SVTs in Group A was 31% (25 of 80 patients) and in Group B was 24% (19 of 80 patients). Furthermore, the incidence of postoperative pericarditis was noted in 35% (28 of 80 patients) of Group A and in 19% (15 of 80 patients) in Group B. The authors conclude that male tobacco smokers of Group A tended to have a significantly higher incidence of postoperative pericarditis with a higher trend for postoperative SVTs than patients from Group B.

Aged↗
PubMed1991

Molecular cloning and expression of the rat beta 3-adrenergic receptor.

Rat adipose tissues contain atypical beta receptors that display certain pharmacological sensitivities that are similar to those found in the recently cloned human beta 3 receptor. However, there are also certain pharmacological differences between the human atypical beta 3 receptor and atypical receptors in rodent adipose tissues, which could indicate strong species differences, the existence of multiple atypical receptor subtypes, or both. To help decide among these possibilities, a rat beta 3 receptor clone was obtained and expressed in Chinese hamster ovary cells. The predicted primary structures of the rat and human receptors are greater than 90% similar. Despite this similarity, the pharmacological properties of the rat receptor differed from those reported for the human receptor but were similar to the properties exhibited by atypical receptors in rat adipose tissue. Specifically, the rat beta 3 receptor had a high affinity for BRL 37344 and a relatively low affinity for norepinephrine and was partially activated by the beta 1 and beta 2 receptor antagonist CGP 12177. Northern blot analysis and nuclease protection assays of RNA from rat tissues indicate that the beta 3 receptor is abundantly expressed only in adipose tissues.

Adenylyl Cyclases↗
PubMed1990

Lymphocyte proliferative response to fertilization antigen in patients with antisperm antibodies.

The fertilization antigen, immunopurified from human testes, activated lymphocytes from three of the six men and women with antisperm antibodies. Lymphocytes from none of the six men and women without antibodies were activated with fertilization antigen. Another sperm surface antigen, the germ cell antigen, immunopurified from murine testes, did not activate lymphocytes from any of the individuals with or without antisperm antibodies. These results indicate that the men and women with antisperm antibodies are sensitized against fertilization antigen and not germ cell antigen. These results reinforce our previous findings on the involvement of fertilization antigen in immunoinfertility in humans.

Animals↗