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Biomedical subjects

C Bose

Publications and source records attributed to C Bose.

At least 19 recordsLinked to original sources
PubMed2007

Nicotine-induced proliferation of isolated rat pancreatic acinar cells: effect on cell signalling and function.

OBJECTIVES: The aim of the current study was to investigate whether nicotine treatment would induce the proliferation of isolated rat primary pancreatic acinar cells in culture by activating mitogen-activated protein kinase (MAPK) signalling and exocrine secretion. MATERIALS AND METHODS: A nicotine dose- and time-response curve was initially developed to determine the optimal dose and time used for all subsequent studies. Proliferation studies were conducted by cell counting and confirmed further by bromodeoxyuridine (BrdU) incorporation and flow cytometry assays. MAPK signalling studies were conducted by Western blot analysis. Localization of ERK1/2 signals, with or without nicotine and the MAPK inhibitor, was visualized by immunofluorescence. RESULTS: Nicotine treatment caused dose-dependent activation of extracellular signal-regulated kinases (ERK1/2), the maxima occurring at 100 micro m and at 3 min after treatment; the response was suppressed by the ERK1/2 inhibitor. Maximal nicotine-induced cell proliferation occurred at 24 h, and UO126-treatment significantly reduced this response. Exposure of cells to 100 microm nicotine for 6 min significantly enhanced both baseline and cholecystokinin-stimulated cell function, and these effects were not affected by treatment with the inhibitor of ERK1/2 but were suppressed by mecamylamine, a nicotinic receptor antagonist. CONCLUSIONS: Our results suggest that nicotine treatment induced cell proliferation of isolated pancreatic acinar cells and that this is coupled with the activation of MAPK signalling with no effect on its function. Hence, in primary cells, the mechanism of induction and regulation of these two processes, cell proliferation and cell function, by nicotine treatment are independent of each other.

Amylases↗
PubMed2001

Physiological regulation of the immunological synapse by agrin.

T cell activation is dependent on both a primary signal delivered through the T cell receptor and a secondary costimulatory signal mediated by coreceptors. Although controversial, costimulation is thought to act through the specific redistribution and clustering of membrane and intracellular kinase-rich lipid raft microdomains at the contact site between T cells and antigen-presenting cells. This site has been termed the immunological synapse. Endogenous mediators of raft clustering in lymphocytes have not been identified, although they are essential for T cell activation. We now demonstrate that agrin, an aggregating protein crucial for formation of the neuromuscular junction, is also expressed in lymphocytes and is important in reorganization of membrane lipid microdomains and setting the threshold for T cell signaling. Our data show that agrin induces the aggregation of signaling proteins and the creation of signaling domains in both immune and nervous systems through a common lipid raft pathway.

Agrin↗
PubMed2001

Mediators of fetal inflammation in extremely low gestational age newborns.

To establish levels of mediators of inflammation in cord blood and postnatal serum from extremely low gestational age newborns (ELGANs, < or =28 weeks), we measured sixteen markers of inflammation by recycling immunoaffinity chromatography in 15 ELGANs who had serum sampled at days 2-5. Median levels of IL-1, IL-6, IL-8, IL-11, IL-13, TNF-alpha, G-CSF, M-CSF, GM-CSF, MIP-1alpha, and RANTES were considerably higher than published values of these inflammatory mediators from term newborns. In three of eight ELGANS who had serial measurements taken, levels of IL-1, IL-6, IL-8, IL-11, TNF-alpha, G-CSF, and MIP-1alpha declined from initially very high levels to reach an apparent baseline towards the end of the first postnatal week. In these same three infants, GM-CSF and TGF-beta1 levels increased continuously during the first week. In the other five ELGANs, no consistent changes were observed. We speculate, that in some ELGANs, a fetal systemic inflammatory response is characterized by an antenatal wave of pro-inflammatory cytokines, followed by a second, postnatal wave of anti-inflammatory cytokines. Large epidemiologic studies are needed to clarify relationships among inflammation markers and their expression in the fetal and neonatal circulation over time. Such studies would also add to our understanding of the possible role of inflammatory mediators in the pathophysiology of the major complications of extreme prematurity.

Adult↗
PubMed2001

A logit model for the effect of telecardiology on acute newborn transfers.

UNLABELLED: The deregionalization of neonatal intensive care in the United States has shifted the site of care for many newborn infants away from academic medical centers where subspecialty support is available. OBJECTIVE: To investigate the effect of immediate echocardiogram interpretation via telemedicine on rates of neonatal transfer to academic medical centers. METHODS: A logit model was developed to predict the probability of transfer from two regional level 3 neonatal intensive care units to academic medical centers. One of these units implemented a telecardiology program and the other acted as a comparison institution with on-site cardiology expertise. The telecardiology intervention began 18 months into the 36-month study period. SUBJECTS: Infants (n = 2,142) admitted to neonatal intensive care at either of the two institutions during calendar years 1994 through 1996. RESULTS: A statistically significant reduction in the rate of transfer to academic medical centers was observed. Telecardiology was associated with a 58% reduction of such transfers (p = .001, 95% CI = 30%, 75%). No such reduction was noted at the comparison institution. It is estimated that approximately 30 transfers were eliminated during the study period, resulting in the elimination of approximately $150,000 in hospital charges. In addition, the infants that were transferred after the adoption of telemedicine were more often transferred to their telemedicine partner institution (p < .02).

Academic Medical Centers↗
PubMed2000

Physiological effects of sound on the newborn.

Excessive sound is an acknowledged problem in neonatal intensive care units (NICUs); however, there is relatively little objective information about the effects of sound on the newborn. The cardiovascular and respiratory systems have been the most extensively studied systems. The patterns of response in these systems may be influenced by a variety of factors, including: the intensity of the sound, the infant's behavioral state, the infant's maturity and postnatal age, and the perinatal history. This article reviews the known cardiovascular, respiratory, and other physiological effects of sound on neonates.

Cardiovascular Physiological Phenomena↗
PubMed2000

Serum inhibin, activin and follistatin in postmenopausal women with epithelial ovarian carcinoma.

OBJECTIVE: To investigate the role of serum inhibin A, inhibin pro-alphaC immunoreactivity, activin A, and follistatin in postmenopausal women with epithelial ovarian cancer. DESIGN: Case-control study. SAMPLE: e Serum samples from 27 postmenopausal women with epithelial ovarian cancer and 54 controls from the general population participating in an ovarian cancer screening trial. RESULTS: Women with epithelial ovarian cancer had significantly higher serum levels of pro-alphaC immunoreactivity (P = 0.03), activin A (P = 0.004) and follistatin (P = 0.04), but not inhibin A (P = 0.13). Using the 90th centile in the control group as the cut off, pro-alphaC levels were elevated in 41% of women with epithelial ovarian cancer, while inhibin A was elevated in only 15%. Using the 95th centile as the cut off, serum pro-alphaC was elevated in only 11% of women with epithelial ovarian cancer (3/27), while activin A was elevated in 48% (11/23). Follicle stimulating hormone levels were significantly lower in women with epithelial ovarian cancer (P = 0.01). Although, inhibin-related peptides can modulate follicle stimulating hormone levels, there was no correlation between inhibin A, pro-alphaC immunoreactivity, activin A or follistatin and follicle stimulating hormone. CONCLUSION: These data demonstrate that though there is preferential secretion of precursor forms of the alpha subunit rather than dimeric inhibin A by epithelial ovarian cancer, pro-alphaC is unlikely to be a useful tumour marker. Activin A is more commonly elevated in postmenopausal women with epithelial ovarian cancer and its role as a tumour marker in the diagnosis and screening of epithelial ovarian cancer warrants further evaluation.

Activins↗
PubMed1996

Continuous negative extrathoracic pressure in neonatal respiratory failure.

OBJECTIVE: In uncontrolled clinical trials, negative extrathoracic pressure has been shown to be an effective respiratory support. We aimed to assess its role in the context of current neonatal intensive care. DESIGN: A randomized controlled trial, with sequential analysis of matched pairs of infants. Matching was undertaken by stratified randomization from 15 groups divided according to gestational age, oxygen requirement, and whether patients were intubated at 4 hours of age. SETTING: Two neonatal intensive care units. PATIENTS: Two hundred forty-four patients (birth weight 1.53 +/- 0.69 kg (mean +/- SD); gestational age 30.4 +/- 3.5 weeks) with respiratory failure. INTERVENTIONS: Patients were randomized at 4 hours of age to receive either standard neonatal intensive care, or standard care plus continuous negative extrathoracic pressure (CNEP, -4 to -6 cmH2O) applied within a purpose-designed neonatal incubator. OUTCOME SCORES: Clinical scores were calculated for each infant at 56 days of age, or death if earlier. Scores included measures for mortality, respiratory outcome, the presence of cerebral ultrasound abnormalities, patent arterial duct, necrotizing enterocolitis, and retinopathy. The treatment given for the higher score for each pair was recorded and the cumulative net number of pairs favoring CNEP plotted in the sequential analysis to provide an ethical early termination strategy. Individual components of the outcome score and other secondary measurements were analyzed on completion of the trial. RESULTS: The sequential analysis reached a decision boundary after 122 out of a possible maximum of 124 pairs were completed. The overall outcome score showed an overall significant benefit for CNEP. Secondary analysis showed that the use of CNEP was associated with an increase in mortality, cranial ultrasound abnormalities, and pneumothoraces, which were not statistically significant. However, 5% fewer patients were intubated (95% confidence interval [CI], 0-10), and the total duration of oxygen therapy among surviving infants at 56 days was lower (20.5 days, compared with 38.9 in controls; difference 18.4 days, 95% CI 3.8 to 33.0). Among all infants, the mean total duration of oxygen therapy was 18.3 days among CNEP-treated infants compared with 33.6 days among the controls (difference -15.3 days, 95% CI -0.2 to -30.4). This reduction in mean levels is entirely attributable to substantially fewer patients requiring prolonged oxygen therapy, the median duration of treatment being very similar in the two groups. As a result, commensurately fewer surviving infants showed chronic lung disease of prematurity. CONCLUSIONS: The use of continuous negative pressure improves the respiratory outcome for neonates with respiratory failure.

Female↗
PubMed1994

Carboline antifilarials: effects on carbohydrate metabolising enzymes in Litomosoides carinii female.

Two antifilarial compounds, viz., 90/55 (7-oxo-1-phenyl-8, 14-dihydropyrido (3,4-b) imidazo (1,2-c) quinazolo (4,5-g) and 87/639 (6-Nitro-1-phenyl-9H-pyrido (3,4-b) indole at 0.5 and 2.0 micron concentrations substantially inhibited glucose uptake and increased lactate production by L. carinii during in vitro incubation for 2 hr. The treated parasites, showed increased activities of glycogen phosphorylase, phosphofructokinase and pyruvate kinase. Hexokinase and fumarate reductase activities level in the worms were significantly lowered. Therefore it appears that both the compounds kill adult L. carinii by interfering with its carbohydrate metabolism.

Animals↗
PubMed1992

Results of laboratory surveillance of very low birth weight infants treated with a synthetic surfactant.

During two randomized, controlled trials comparing single prophylactic doses of air placebo and a synthetic surfactant, Exosurf Neonatal, many routine laboratory measurements were made in small premature infants during the first week of life. Values for serum electrolytes, urea, creatinine, phospholipid, cholesterol, glucose, calcium, bilirubin, and liver enzymes, as well as for hemoglobin, leukocyte and platelet counts, and urinalysis, did not differ between the placebo- and surfactant-treated infants. There was no evidence that prophylactic administration of this synthetic surfactant causes alterations in standard laboratory tests in small premature infants.

Blood↗
PubMed1992

Trial of vitamin A supplementation in very low birth weight infants at risk for bronchopulmonary dysplasia.

We performed a randomized, double-blind, controlled trial to determine whether vitamin A supplementation in a group of very low birth weight infants would reduce the incidence of bronchopulmonary dysplasia. Forty-nine infants (birth weight 700 to 1100 gm) requiring mechanical ventilation and supplemental oxygen at 96 hours age were randomly assigned to receive either 2000 IU retinyl palmitate (n = 27) or saline placebo (n = 22) intramuscularly every other day for up to 14 doses. There were no differences between treatment groups in the incidences of bronchopulmonary dysplasia at 31 days of postnatal age (vitamin A group 48%, placebo group 55%; p = 0.776), supplemental oxygen requirement at 34 weeks of postconceptional age, or other complications of prematurity. The vitamin A group had higher mean plasma vitamin A concentrations than the placebo group, but mean plasma vitamin A concentrations were greater than 20 micrograms/dl (suggesting sufficiency) in both groups after the first study week. By study day 28, only one fourth of the infants in either group had plasma vitamin A concentrations less than 20 micrograms/dl. In contrast to an earlier report, we found no change in the incidence of BPD with vitamin A supplementation. Our findings may reflect a low baseline incidence of vitamin A deficiency in the study population and recent changes in the respiratory care of very low birth weight infants. The latter may have lessened the potential impact of vitamin A deficiency on lung disease.

Bronchopulmonary Dysplasia↗
PubMed1992

Involvement of beta 2-adrenoceptors in the regional haemodynamic responses to bradykinin in conscious rats.

1. Bradykinin can release neuronal calcitonin gene-related peptide (CGRP) and adrenal medullary catecholamines, both of which could contribute to its cardiovascular effects in vivo. Therefore, in the main experiment, regional haemodynamic responses to bolus injections of bradykinin (3 nmol kg-1, i.v.) were assessed in the same chronically-instrumented, conscious, Long Evans rats in the absence and in the presence of human alpha-CGRP [8-37] or ICI 118551, antagonists of CGRP1-receptors and beta 2-adrenoceptors, respectively. The selected doses of these antagonists caused specific inhibition of responses mediated by exogenous human alpha-CGRP and beta 2-adrenoceptor agonists, respectively. 2. Bradykinin administered alone as an i.v. bolus had a slight pressor effect accompanied by a marked tachycardia. There were early (at about 30 s) increases in flow and conductance in the mesenteric vascular bed, and delayed (at about 90 s), but qualitatively similar, changes in the hindquarters vascular bed. There were only slight increases in flow and conductance in the renal vascular bed. 3. Human alpha-CGRP [8-37] had no statistically significant effects on the responses to bolus doses of bradykinin. However, in the presence of ICI 118551, the pressor effect of bradykinin was significantly enhanced while its tachycardic effect was significantly suppressed. The hindquarters vasodilator effect of bradykinin was converted to a vasoconstriction and there was a slight renal vasoconstriction, but the mesenteric vasodilator effect of bradykinin was unchanged by ICI 118551. 4. In subsidiary experiments, in other animals, it was found that infusion of bradykinin (36 nmol kg-1 min-1) elicited a pattern of haemodynamic responses similar to that seen with bolus injections and, as in the latter case, the hindquarters hyperaemic vasodilation was inhibited by ICI 118551. In the presence of mecamylamine (at a dose sufficient to block reflex heart rate responses to rises or falls in arterial blood pressure) bolus injection or infusion of bradykinin still elicited increases in renal, mesenteric and hindquarters blood flow. However, in additional experiments in adrenal demedullated rats (n = 4) the hindquarters hyperaemic effect of bradykinin was absent, although the mesenteric hyperaemic effect remained. 5. The results indicate that the increase in hindquarters blood flow following administration of bradykinin in vivo is largely due to activation of beta 2-adrenoceptors by catecholamines released subsequent to direct stimulation of the adrenal medulla by the peptide. However, the bradykinin-induced increase in mesenteric blood flow does not depend on this mechanism.

Adrenal Medulla↗
PubMed1992

Pharmacological characterization of a receptor for calcitonin gene-related peptide on rat, L6 myocytes.

1 The L6 myocyte cell line expresses high affinity receptors for calcitonin gene-related peptide (CGRP) which are coupled to activation of adenylyl cyclase. The biochemical pharmacology of these receptors has been examined by radioligand binding or adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation. 2 In intact cells at 37 degrees C, human and rat alpha- and beta-CGRP all activated adenylyl cyclase with EC50s of about 1.5 nM. A number of CGRP analogues containing up to five amino acid substitutions showed similar potencies. In membrane binding studies at 22 degrees C in 1 mM Mg2+, the above all bound to a single site with IC50s of 0.1-0.4 nM. 3 The fragment CGRP(8-37) acted as a competitive antagonist of CGRP stimulation of adenylyl cyclase with a calculated Kd of 5 nM. The Kd determined in membrane binding assays was lower (0.5 nM). 4 The N-terminal extended human alpha-CGRP analogue Tyro-CGRP activated adenylyl cyclase and inhibited [125I]-iodohistidyl-CGRP binding less potently than human alpha-CGRP (EC50 for cyclase = 12 nM, IC50 for binding = 4 nM). 5 The pharmacological profile of the L6 CGRP receptor suggests that it most closely resembles sites on skeletal muscle, cardiac myocytes and hepatocytes. The L6 cell line should be a stable homogeneous model system in which to study CGRP mechanisms and pharmacology.

Animals↗
PubMed1991

Structural studies on the [Bu(t)-Cys18](19-37)-fragment of human beta-calcitonin-gene-related peptide.

High-field n.m.r. studies were undertaken upon a peptide fragment of the C-terminal region of human beta-calcitonin-gene-related peptide (beta-hCGRP). Studies on the antigenic [Bu(t)-Cys18]beta-hCGRP-(19-37)-fragment revealed that several elements of secondary structure were present when the peptide was dissolved in [2H6]dimethyl sulphoxide. In particular an unspecified turn in the region of Ser19-Gly20 and a type I beta-turn in the region of Asn31-Val32-Gly33 were identified. Through-space connections between the terminal Phe37 amide group and the beta-protons of Thr50 suggest that the peptide may be folded into a loop-type conformation. These structural elements appear to overlap with the epitopes of a number of monoclonal antibodies and provide a molecular basis for understanding the role of the terminal Phe37 amide residue in the immune recognition of beta-hCGRP.

Amino Acid Sequence↗
PubMed1991

Differential vasodilator profile of calcitonin gene-related peptide in porcine large and small diameter coronary artery rings.

The vasodilator profile of calcitonin gene-related peptide (CGRP) was compared in large diameter (3-4 mm outer diameter) and small diameter (less than 1 mm outer diameter) rings from porcine left anterior descending coronary arteries (LAD). CGRP relaxed both sized rings in an endothelium-independent manner but was 10 X more potent in small compared to large diameter rings. Repeated administration of CGRP to small diameter rings did not cause the development of tolerance to its effects, whereas in the large diameter rings marked tolerance developed. Pretreatment with the CGRP peptide fragment, CGRP-(8-37) antagonised the vasodilator effects of CGRP in a concentration-dependent manner, but in large diameter rings, the antagonistic potency of CGRP-(8-37) was 10 X less than that seen in the small diameter rings. This differing vasodilator profile of CGRP in small and large diameter rings of pig LADs may be related to a differential CGRP receptor distribution along their length.

Acetylcholine↗
PubMed1991

Human alpha-calcitonin gene-related peptide (CGRP)-(8-37), but not -(28-37), inhibits carotid vasodilator effects of human alpha-CGRP in vivo.

Human alpha-calcitonin gene-related peptide-(8-37) alone (up to doses of 30 nmol kg-1 min-1) had no significant effects on blood pressure, heart rate or common or internal carotid haemodynamics, although it caused significant, reversible, inhibition of the hypotensive, tachycardic, and common and internal carotid vasodilator effects of human alpha-CGRP (0.03 nmol kg-1 min-1) in conscious, Long Evans rats. Human alpha-CGRP-(28-37) up to doses of 300 nmol kg-1 min-1 had no cardiovascular effects itself and did not influence responses to human alpha-CGRP. These results are consistent with the carotid haemodynamic effects of human alpha-CGRP being due largely to activation of the CGRP1-receptor subtype.

Animals↗
PubMed1991

Solution structures of calcitonin-gene-related-peptide analogues of calcitonin-gene-related peptide and amylin.

Near-u.v. and far-u.v. c.d. spectra of human alpha-calcitonin-gene-related peptide (h alpha CGRP), analogues and fragments of CGRP and amylin were recorded in aqueous solution and in trifluoroethanol (TFE)/water mixtures. All peptides contained significant amounts of alpha-helix in aqueous solution, and this amount increased on adding TFE. The helical content was unaffected by pH and salt. However, amylin contained much less helix than CGRP and the c.d. spectrum was more temperature-sensitive. A band in the near-u.v. c.d. spectrum of CGRP (but not present in the spectrum of amylin) was attributed to the disulphide bond in CGRP. The intensity of this band was pH-dependent and titrated with a pKa of 6.5, suggesting the involvement of histidine ionization.

Amino Acid Sequence↗
PubMed1991

Antagonistic effect of human alpha-calcitonin gene-related peptide (8-37) on regional hemodynamic actions of rat islet amyloid polypeptide in conscious Long-Evans rats.

Rat synthetic amidated islet amyloid polypeptide (IAPP) was infused into conscious Long-Evans rats chronically instrumented for the measurement of regional hemodynamics. Rat IAPP (0.25-2.5 nmol.kg-1.min-1) had dose-dependent tachycardiac and hypotensive effects. Renal blood flow increased at all dose levels in association with incremental rises in renal vascular conductances. Hindquarters blood flow and vascular conductance increased at the higher dose levels, but mesenteric blood flow fell with mean arterial blood pressure (i.e., there was no change in mesenteric vascular conductance). Concurrent infusion of 25 nmol.kg-1.min-1 human alpha-calcitonin gene-related peptide (CGRP) (8-37) abolished the hypotensive, tachycardiac, and renal and hindquarters vasodilator effects of rat IAPP, and during administration of both peptides, there was a transient renal and sustained mesenteric vasoconstriction. When the infusion of human alpha-CGRP (8-37) was stopped, the effects of the continued infusion of rat IAPP were reestablished. The results indicate that the reported ability of IAPP to induce insulin resistance cannot be due to decreased skeletal muscle blood flow. In addition, human alpha-CGRP (8-37) is an effective antagonist of the hemodynamic actions of rat IAPP. Because it has been shown previously that human alpha-CGRP (8-37) antagonizes the hemodynamic effects of human alpha-CGRP, these results, collectively, indicate that human alpha-CGRP and rat IAPP might act on the same receptor at which human alpha-CGRP (8-37) is an effective antagonist or that the latter is a nonselective antagonist of separate receptors on which human alpha-CGRP and rat IAPP act.

Amyloid↗