Search PubMed⌕ Search

Biomedical subjects

C Chen

Publications and source records attributed to C Chen.

At least 991 records · Page 55Linked to original sources
PubMed1993

Amylin modulates beta-cell glucose sensing via effects on stimulus-secretion coupling.

The release of insulin from the pancreatic beta cell is dependent upon a complex interplay between stimulators and inhibitors. Recently, amylin, a peptide secreted by pancreatic beta cells, has been implicated in the development of type II (noninsulin dependent) diabetes through its modulation of the peripheral effects of insulin. However, the effect of amylin on insulin secretion from the beta cell has remained controversial. It is reported here that in single beta cells exhibiting normal glucose sensing, amylin causes membrane hyperpolarization, increases in net outward current, and reductions in insulin secretion. In contrast, in cells with abnormal glucose sensing (e.g., from db/db diabetic mice), amylin has no effect on electrical activity or secretion. Thus, amylin's effects on excitation-secretion coupling in the beta cell of the pancreas appear to be linked to the cell's capacity for normal glucose sensing.

Amyloid↗
PubMed1993

Detection, isolation and characterization of multiple lectins from the haemolymph of the cockroach Blaberus discoidalis.

Three agglutinins (lectins), designated BDL1, BDL2 and BDL3, were identified in the haemolymph of the cockroach Blaberus discoidalis by erythrocyte cross-adsorption and sugar inhibition tests. With the use of (NH4)2SO4 fractionation, anion-exchange and affinity chromatography, BDL1 and BDL2 have been purified to homogeneity, and BDL3 has been partially purified to three bands on SDS/PAGE. BDL1 has a molecular-mass estimate of 390 kDa by gel filtration and approx. 158 kDa by SDS/PAGE under non-reducing conditions, further reduced to subunits of 36 kDa under reducing conditions. BDL2 has a molecular mass of approx. 140 kDa and is composed of subunits of 67 kDa which can be further reduced to identical subunits of 23 kDa. Isoelectric focusing in agarose gels revealed that BDL1 and BDL2 both focused as single bands at pH 6.0 and pH 5.2 respectively. The purified forms of BDL1 and BDL2 were stained by the periodic acid/Schiff's reagent showing that both lectins are glycoproteins. In addition, BDL1 was deglycosylated by endo-beta-N-acetylglucosaminidase H. Immunological tests showed that these three lectins are not structurally related. All three lectins bind galactose but have different specificities for binding other sugars and for a range of vertebrate erythrocytes. BDL1 is specifically inhibited by D-(+)-glucose, D-(+)-mannose and N-acetyl-D-mannosamine, but not by N-acetyl-D-glucosamine, and BDL2 is inhibited by N-acetyl-D-glucosamine, but not by D-(+)-glucose, D-(+)-mannose or N-acetyl-D-mannosamine. BDL3 is strongly inhibited by N-acetyl-D-galactosamine, but not by any of the other above-mentioned sugars. Erythrocyte specificities showed that BDL1 is more specific for rabbit than mouse erythrocytes, whereas BDL2 and BDL3 are more specific for mouse than rabbit erythrocytes. The haemagglutinating activities of both the serum and isolated lectins are Ca(2+)-dependent. Localization of BDL1 and BDL2 with fluorescein isothiocyanate-labelled antibodies showed that both lectins are associated with the granules and other areas of the cytoplasm of all blood cell types.

Animals↗
PubMed1993

Age-dependent changes in the phosphorylation of nuclear proteins of submandibular glands in isoproterenol-treated rats.

Age-dependent changes in the regulation of the phosphorylation of nuclear proteins were investigated in relation to DNA synthesis in rat submandibular glands after injection of isoproterenol (IPR). The level of phosphorylation of nuclear proteins in the tissue increased rapidly after birth, reaching a maximum at 4 weeks, and then decreased to the level of 52-week-old rats. The level of protein kinase activity in nuclei varied in parallel with that of phosphorylation of nuclear non-histone proteins after birth. The time after the injection of IPR required to initiate the phosphorylation of nuclear non-histone proteins of rat submandibular glands, which occurs prior to the onset of RNA synthesis that precedes the replication of DNA, increased with age. These results suggest that this delayed onset of phosphorylation plays a regulatory role in cell proliferation and cell function during aging.

Aging↗
PubMed1993

Human growth hormone releasing factor (hGRF) modulates calcium currents in human growth hormone secreting adenoma cells.

Electrophysiology of human growth hormone secreting tumour cells and its modification by hGRF has been studied using on-cell and Nystatin-perforated whole-cell recording configurations. Local application of hGRF (10 nM) produced an increase in the frequency of action potentials. Ca2+ currents were isolated by a ramp depolarizing pulse from -120 mV to +60 mV in the presence of tetrodotoxin (1 microM). Human GRF increased the Ca2+ currents which could be blocked by Ni+ (300 microM). We conclude that an increase in Ca2+ current is integral to the action of hGRF on these cells.

Action Potentials↗
PubMed1993

Vasopressin induction of long-lasting potentiation of synaptic transmission in the dentate gyrus.

Vasopressin receptors are present in both the developing and mature dentate gyrus of the rat brain and are of the V1 vasopressor type. Because vasopressin has been shown to influence memory function when injected into the dentate gyrus, the influence of this peptide on an electrophysiological model of learning and memory using the field excitatory postsynaptic potential (EPSP) of the dentate gyrus was investigated. Results of these studies showed that nanomolar concentrations of [Arg8]-vasopressin induced a prolonged increase in the amplitude and slope of the evoked population response in the presence of 1.5 mM calcium. Moreover, the expression of the vasopressin-induced potentiation of the EPSP persisted following removal of vasopressin from the perfusion medium. The vasopressin-induced sustained increase has been termed long-term vasopressin potentiation (LTVP). The closely related neuropeptide oxytocin had no effect upon the EPSP of the dentate gyrus. Preincubation of hippocampal slices in a selective V1 antagonist blocked the expression of LTVP. The ability of the V1 antagonist to block LTVP demonstrates that the potentiation induced by vasopressin is receptor-specific. In the presence of 2.5 mM calcium, the effect of vasopressin was opposite to that observed in 1.5 mM calcium. Under the conditions of 2.5 calcium, vasopressin induced a prolonged depression in the amplitude and slope of the EPSP. Expression of both potentiation and depression appeared within 5 minutes of application and persisted for the length of the observation, 60 minutes. These experiments demonstrate that vasopressin can induce long-lasting changes in the excitability of dentate gyrus neurons that are both calcium-dependent and receptor-specific.

Animals↗
PubMed1993

Involvement of the Golgi region in the intracellular trafficking of cholera toxin.

The intracellular pathway following receptor-mediated endocytosis of cholera toxin was studied using brefeldin A (BFA), which inhibited protein secretion and induced dramatic morphological changes in the Golgi region. In both mouse Y1 adrenal cells and CHO cells, BFA at 1 micrograms/ml caused a 80-90% inhibition of the cholera toxin (CT)-induced elevation of intracellular cAMP. The inhibition of the cytotoxicity of CT by BFA was also observed in a rounding assay of Y1 adrenal cells. The inhibition of CT cytotoxicity by BFA was dose dependent, with the ID50 value similar to the LD50 of BFA in Y1 adrenal cells. Binding and internalization of [125I]-labeled cholera toxin in Y1 adrenal cells was not affected by BFA. Unlike the BFA-sensitive cell lines such as Y1 adrenal and CHO cells, BFA at 1 micrograms/ml did not inhibit the cytotoxicity of CT in PtK1 cells, of which the Golgi structure was BFA-resistant. These results strongly suggest that a BFA-sensitive Golgi is required for the protection of CT cytotoxicity by BFA. In contrast, elevation of the intracellular cAMP by forskolin, which acts directly on the plasma membrane adenylate cyclase, was not affected by BFA. These observations indicate that the intoxication of target cells by CT requires an intact Golgi region for its intracellular trafficking and/or processing. In this respect, CT shares a common intracellular pathway with ricin, Pseudomonas toxin, and modeccin, even though their structures and modes of action are very different.

Animals↗
PubMed1993

Quantitative assessment of cancer risk from exposure to diesel engine emissions.

Quantitative estimates of lung cancer risk from exposure to diesel engine emissions were developed using data from three chronic bioassays with Fischer 344 rats. Human target organ dose was estimated with the aid of a comprehensive dosimetry model. This model accounted for rat-human differences in deposition efficiency, normal particle clearance rates, transport of particles to lung-associated lymph nodes, respiration rates, and lung surface area, as well as high-dose inhibition of particle clearance. Recent evidence indicates that the inert carbon core of the diesel particulate matter is likely to be the primary source of carcinogenicity. The epithelial tissue lining the alveoli and lower airways is the primary target site for induction of lung tumors. Dose was therefore based upon the concentration of carbon particulate matter per unit lung surface area. Unit risk estimates were developed using either a time-to-tumor or a linearized multistage model. The unit risk estimates, defined as the 95% upper confidence limit of the cancer risk from continuous lifetime exposure to 1 microgram/m3 of diesel exhaust particulate matter, varied from 1.0 to 4.6 x 10(5) with a geometric mean of 1.7 x 10(5).

Animals↗
PubMed1993

Inhibition of Na+,K(+)-ATPase in rat renal proximal tubules by dopamine involved DA-1 receptor activation.

Endogenous kidney dopamine (DA) causes natriuresis and diuresis, at least partly, via inhibition of proximal tubular Na+,K(+)-ATPase. The present study was done to identify the dopamine receptor subtype(s) involved in dopamine-induced inhibition of Na+,K(+)-ATPase activity. Suspensions of renal proximal tubules from Sprague-Dawley rats were incubated with dopamine, the DA-1 receptor agonist fenoldopam or the DA-2 receptor agonist SK&F 89124 in the presence or absence of either the DA-1 receptor antagonist SCH 23390 or the DA-2 receptor antagonist domperidone. Dopamine and fenoldopam (10(-5) to 10(-8) mol/l) produced a concentration-dependent inhibition of Na+,K(+)-ATPase activity. However, SK&F 89124 failed to produce any significant effect over the same concentration range. Incubation with fenoldopam (10(-5) to 10(-8) mol/l) in the presence of SK&F 89124 (10(-6) mol/l) inhibited Na+,K(+)-ATPase activity to a degree similar to that with fenoldopam alone. Furthermore, DA-induced inhibition of Na+,K(+)-ATPase activity was attenuated by SCH 23390, but not by domperidone. Since alpha-adrenoceptor activation is reported to stimulate Na+,K(+)-ATPase activity and, at higher concentrations, dopamine also acts as an alpha-adrenoceptor agonist, the potential opposing effect from alpha-adrenoceptor activation on DA-induced inhibition of Na+,K(+)-ATPase activity was investigated by using the alpha-adrenoceptor blocker phentolamine. We found that, in the lower concentration range (10(-5) to 10(-7) mol/l), dopamine-induced inhibition of Na+,K(+)-ATPase activity in the presence of phentolamine was similar in magnitude to that observed with dopamine alone.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

VirR and Mry are homologous trans-acting regulators of M protein and C5a peptidase expression in group A streptococci.

Transcription of the group A streptococcal M12 protein gene (emm12) and the C5a peptidase gene (scpA), which encodes an inhibitor of complement-mediated chemotaxis, was previously shown to depend on a third genetic locus, designated virR. A 1.6 kb region of DNA which is 200 bp upstream of emm12 and is thought to contain the virR locus, was sequenced. An open reading frame which overlaps deletion mutations that define virR was identified. The sequence of the encoded VirR protein, which was deduced to contain 499 amino acids, is characteristic of cytoplasmic proteins. Comparison of the VirR protein to a variety of DNA binding proteins, such as lambda Cro, revealed a DNA binding motif. VirR was also compared to the M6 positive regulator, mry, and found to be 98% homologous. The predicted virR promoter is preceded by two sets of inverted repeats, in contrast to mry which is preceded by one repeat. Introduction of virR on the shuttle vector pAM401 into a strain of group A Streptococcus with a deletion in the chromosomal virR gene demonstrated that the VirR protein activated transcription of both emm12 and scpA genes in trans. Analysis of RNA by Northern blot using virR-specific probes identified two virR transcripts, a 1.6 kb transcript which corresponds to the predicted size of the gene, and a second transcript, 3.5 kb, which also overlaps virR. These results demonstrate that virR and mry are structurally and functionally very similar and show that the former is a trans activator of both M protein and C5a peptidase synthesis.

Adhesins, Bacterial↗
PubMed1993

Beta-cell hypersensitivity for glucose precedes loss of glucose-induced insulin secretion in 90% pancreatectomized rats.

Glucose-induced insulin secretion is impaired in the presence of chronic hyperglycaemia. Insulin secretion was studied in a diabetic rat model prior to the beta cells becoming non-responsive to glucose in order to map out the sequence of changes that accompany chronic hyperglycaemia. In vitro pancreas perfusions were carried out 1 and 2 weeks after a 90% pancreatectomy; controls underwent a sham pancreatectomy. One week post 90% pancreatectomy: (i) non-fasting plasma glucose values were 2-3 mmol/l above normal, (ii) the in vitro insulin response to 16.7 mmol/l glucose was 20 +/- 4% of shams, a response that was appropriate for the surgical reduction in beta-cell mass, (iii) the beta-cell sensitivity for glucose was increased as reflected by left-shifted dose-response curves for glucose-induced insulin secretion (half maximal insulin output 5.7 mmol/l glucose vs 16.5 mmol/l glucose in shams) and glucose potentiation of arginine-induced insulin secretion (half maximal insulin output 3.5 mmol/l glucose vs 14.8 mmol/l glucose in shams). This heightened beta-cell sensitivity for glucose was not a result of the hyperglycaemia, because similarly reduced half-maximal insulin responses were found after a 60% pancreatectomy, a surgical procedure in which plasma glucose values remained normal. In summary, a rise in beta-cell sensitivity for glucose precedes the loss of glucose-induced insulin secretion in diabetic rats.

Animals↗
PubMed1993

The effect of starvation on the diurnal variation of amylase secretion from rat parotid glands.

The purpose of this study was to investigate the effect of starvation on the cellular function of rat parotid glands in relation to the diurnal variation of amylase secretion from the tissue. Salivary amylase secreted from the glands of rats starved for 24 h showed diurnal variation, with two peaks at 13 and 21 h. The peak at 21 h was more notable than that in fed rats, because of the accumulation of a large amount of amylase in the tissue due to starvation. Maximal binding (Bmax) values of [3H]dihydroalprenolol in the parotid membrane of starved rats also showed diurnal variation, with marked peak at 13 and 21 h. However, phosphorylation of nuclear non-histone proteins in starved rat parotid glands showed diurnal variation, with peaks at 17 and 1 h. This phasing was delayed by 4 h in comparison to that of fed rats, suggesting that the delay of diurnal variation of amylase secretion commences at least a few days after the beginning of starvation. These results indicate that changes in salivary amylase secreted from parotid glands of rats starved for 24 h coupled with those in the number of beta-adrenoceptors in the tissue show the same diurnal variation as observed in fed rats. Starvation of rats for 24 h does not appear to influence the response of parotid gland cells to stimuli.

Amylases↗
PubMed1993

Biomechanical analysis of the knee extension exercise.

A mathematical analysis of knee extension and flexion exercise is presented to determine effectiveness in strengthening the quadriceps and hamstring muscles. A quantitative relationship between the quadriceps force and the hamstring force is obtained for several variations of the exercises. The theoretical results are supplemented with experimental studies performed on subjects exercising with the Tekdyne Incentive Dynamometer.

Biomechanical Phenomena↗
PubMed1993

The role of myoglobin in retarding oxygen depletion in skeletal muscle.

Myoglobin retards the development of anoxia in a poorly perfused region of skeletal muscle by facilitating diffusion into this region from adjacent normally perfused regions and by releasing bound oxygen directly into the tissue. We examine these phenomena by analyzing a mathematical model of time-dependent myoglobin-facilitated oxygen transport. The governing equations are solved using similarity transformations and multiple-scale techniques. We find that when perfusion of a region is suddenly decreased, oxygen depletion is significantly retarded by direct release of myoglobin-bound oxygen into the tissue and that myoglobin-facilitated diffusion of oxygen from adjacent regions becomes significant at very low oxygen concentration.

Animals↗