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C Chen

Publications and source records attributed to C Chen.

At least 1,045 records · Page 58Linked to original sources
PubMed1992

Synthesis and biological activity of 8a-phenyldecahydroquinolines as probes of PCP's binding conformation. A new PCP-like compound with increased in vivo potency.

The synthesis and chemical resolution of cis- and trans-fused 8a-phenyldecahydroquinolines 3 and 4 are described together with the affinity of the four optically pure compounds for the PCP recognition site of the NMDA receptor complex. These compounds were also evaluated for their antagonistic effects on cGMP levels in male Swiss Webster mice, and (-)-4 was found to exhibit in vivo potency comparable to that of MK-801. The results of the binding studies are interpreted in terms of a preferred orientation of PCP's N-H bond in binding to its NMDA receptor-associated recognition site.

Animals↗
PubMed1992

Peptide/protein structure analysis using the chemical shift index method: upfield alpha-CH values reveal dynamic helices and alpha L sites.

The alpha-CH shifts observed by 1H NMR for medium-sized peptides and for an unusual small protein, herein, which has a high density of alpha L conformations within its 43 residue length, reveal that the recently introduced chemical shift index (CSI) analysis places short dynamic helices (alpha R) and alpha L residues in the same category as stable helices. The method appears to be a promising addition to the arsenal of methods for peptide structure analysis and is clearly not limited to rigid protein systems.

Amino Acid Sequence↗
PubMed1992

Suicide and violence associated with panic attacks.

Several studies have indicated that patients with panic attacks have a higher rate of suicide attempts as well as deaths from suicide. Additionally, several investigators have presented case reports of individuals manifesting suicidal and violent behaviors directly and temporally associated with panic attacks. We report on four additional cases and suggest that these findings may explain, in part, the increased rate of suicidal behavior among patients with panic attacks found by some investigators. Furthermore, these case reports offer preliminary evidence that the relationship between violent behavior and the panic state may be clinically significant and deserving of further elucidation.

Adult↗
PubMed1992

Cloning of the essential myotonic dystrophy region and mapping of the putative defect.

Myotonic dystrophy is a common dominant disorder (global incidence of 1:8,000) with variable onset and a protean nature of symptoms mainly involving progressive muscle wasting, myotonia and cataracts. To define the molecular defect, we have cloned the essential region of chromosome 19q13.3, including proximal and distal markers in a 700-kilobase contig formed by overlapping cosmids and yeast artificial chromosomes (YACs). The central part of the contig bridges an area of about 350 kilobases between two new flanking crossover borders. This segment has been extensively characterized through the isolation of five YAC clones and the subsequent subcloning in cosmids from which a detailed EcoRI, HindIII, MluI and NotI restriction map has been derived. Two genomic probes and two homologous complementary DNA probes were isolated using the cosmids. These probes are all situated within approximately 10 kilobases of genomic DNA and detect an unstable genomic segment in myotonic dystrophy patients. The length variation in this segment shows similarities to the instability seen at the fragile X locus. The physical map location and the genetic characteristics of the length polymorphism is compatible with a direct role in the pathogenesis of myotonic dystrophy.

Blotting, Southern↗
PubMed1992

Differential expression of carboxyl terminal derivatives of amyloid precursor protein among cell lines.

Understanding the pathway for amyloid percursor protein (APP) catabolism has become an important line of investigation. APP is a ubiquitous membrane bound protein that is rapidly cleaved at the membrane, yielding a secreted protein identical to protease nexin II and an internalized 11.5 kDa 100 residue C terminal derivative (CTD). The levels of CTDs in a variety of cell lines have been examined and were found to differ. Cell types associated with the pathology of Alzheimer's disease (AD), such as olfactory neuroblasts (ON) and cortical vascular endothelial cells, have higher levels of CTDs than lymphoblasts and melanoma cells. The mechanism of CTD catabolism appears to involve the lysosome because blockade of lysosomal but not endosomal or mitochondrial function results in increased levels of CTDs. Under these conditions, production of larger, amyloidogenic CTDs is also seen. In cells possessing higher levels of CTDs we find that the mechanism for production of amyloidogenic CTDs may involve the internalization of intact full-length APP. Thus, inhibition of the lysosomal system appears capable of generating amyloidogenic peptides. The amount of amyloidogenic peptides appears to vary among cell lines. Such variation may shed light on why amyloid accumulates around specific cell types such as vascular endothelial cells, neurons, and glia. Finally, disfunction of the lysosomal system may play a role in the pathogenesis of Alzheimer's disease.

Alzheimer Disease↗
PubMed1992

In vivo studies of [125I]iodobenzamide and [11C]iodobenzamide: a ligand suitable for positron emission tomography and single photon emission tomography imaging of cerebral D2 dopamine receptors.

Iodobenzamide (IMB) labeled with either [11C] or [125I] was studied in mice and baboons. Pharmacological studies demonstrated an in vivo binding profile compatible with D2 dopamine receptors. Mouse biodistribution studies with both [11C]IMB and [125I]IMB showed a similar brain distribution of radioactivity. Mouse [125I]IMB studies with amphetamine and reserpine pretreatment suggested that IMB may be less susceptible to endogenous dopamine competition for D2 receptor binding in vivo as compared to raclopride. Preliminary baboon studies showed haloperidol competition for IMB binding sites.

Animals↗
PubMed1992

Diurnal variation of amylase secretion is coupled with alterations of beta-adrenoceptors in the rat parotid gland.

Diurnal changes in the neurotransmitter receptors are important for studying the receptor function in neurophysiology. The purpose of this study is to gain an insight into the regulatory mechanisms of the diurnal variation of amylase secretion. Rat salivary amylase levels showed a diurnal variation with two peaks, a marked peak at 13 h and a lesser peak at 21 h. This increase in salivary amylase levels was completely inhibited by pretreatment of rats with the beta-adrenergic antagonist propranolol, but not by the alpha-adrenergic antagonist phentolamine. Amylase level in parotid tissue homogenate also showed a diurnal change, but there was only one peak, at 13 h. The number of maximal binding sites (Bmax) for [3H]dihydroalprenolol (DHA) in parotid membranes showed a diurnal variation with two marked peaks at 13 and 21 h, but the affinity of parotid beta-adrenoceptors for agonists or antagonists did not show any diurnal changes. Phosphorylation of nuclear non-histone proteins in the rat parotid gland showed diurnal variation with two marked peaks at 13 and 21 h. These results indicate that a diurnal variation in the number of rat parotid beta-adrenoceptors, which is presumably regulated by gene expression, is coupled with a change in salivary amylase secretion.

Amylases↗
PubMed1992

Isovolumic relaxation time varies predictably with its time constant and aortic and left atrial pressures: implications for the noninvasive evaluation of ventricular relaxation.

The isovolumic relaxation time (IVRT) is an important noninvasive index of left ventricular diastolic function. Despite its widespread use, however, the IVRT has not been related analytically to invasive parameters of ventricular function. Establishing such a relationship would make the IVRT more useful by itself and perhaps allow it to be combined more precisely with other noninvasive parameters of ventricular filling. The purpose of this study was to validate such a quantitative relationship. Assuming isovolumic relaxation to be a monoexponential decay of ventricular pressure (pv) to a zero-pressure asymptote, it was postulated that the time interval from aortic valve closure (when pv = p(o)) until mitral valve opening (when pv = left atrial pressure, pA) would be given analytically by IVRT = tau[log(p(o))-log(pA)], where tau is the time constant of isovolumic relaxation and log is to the base e. To test this hypothesis we analyzed data from six canine experiments in which ventricular preload and afterload were controlled nonpharmacologically. In addition, tau was adjusted with the use of beta-adrenergic blockade and calcium infusion, as well as with hypothermia. In each experiment data were collected before and after the surgical formation of mitral stenosis, performed to permit the study of a wide range of left atrial pressures. High-fidelity left atrial, left ventricular, and aortic root pressures were digitized, the IVRT was measured from the aortic dicrotic notch until the left atrioventricular pressure crossover point, and tau was calculated by nonlinear least-squares regression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Factors affecting mitral valve reoperation in 317 survivors after mitral valve reconstruction.

From a very heterogeneous group of 340 patients undergoing mitral valve reconstruction from 1969 through 1988, 313 hospital survivors were analyzed for factors affecting the occurrence of reoperative mitral valve procedures related to native mitral valve dysfunction. Follow-up was 100% and extended from 1 year to 20 years (mean follow-up, 7.2 years). Sixty-three patients (18.5% of the 340) required mitral valve reoperation at a mean postoperative interval of 6 years (range, 1 to 15 years). Incremental risk factors analyzed for the event late mitral valve failure included age, sex, preoperative New York Heart Association class, cause of valvular disease, pathophysiology of the mitral valve, previous mitral valve operation, mitral valve pathology, and estimation of mitral valve function at operation after repair. Mitral valve pathophysiology affected the actuarial freedom from mitral valve replacement (p = 0.023 [log-rank]). Actuarial freedom from mitral valve reoperation was 90% at 5 years and 80% at 8 years in patients who had either pure mitral regurgitation or isolated mitral stenosis compared with 80% and 72% at 5 and 10 years, respectively, in patients who had mixed mitral stenosis and regurgitation (p = 0.023). Patients undergoing late reoperation were younger (51.7 +/- 1.56 years [+/- the standard error of the mean]) than those not having reoperation (p less than 0.0003). Durability of the repair was less in patients with rheumatic heart disease (p less than 0.025) and greater in patients with ischemic heart disease (p less than 0.004). Seventy-three percent of patients undergoing reoperation had concomitant operations compared with 68% of those not having reoperation (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Cryopreserved allograft veins as alternative coronary artery bypass conduits: early phase results.

Traditional autologous conduits are sometimes unavailable or unsuitable to permit total revascularization during coronary artery bypass grafting. In these patients the results of using nonautologous alternative conduits has been disappointing. Encouraged by the excellent long-term results seen with cryopreserved allograft valves, a clinical protocol was developed to evaluate the use of a commercially cryopreserved allograft saphenous vein (CPV). Our protocol consisted of using CPV when left internal mammary arteries and autologous saphenous vein grafts were unavailable or unsuitable for complete revascularization. Blood group (ABO) typed CPVs were thawed and implanted as required using standard surgical techniques. From December 1989 through June 1991, 19 of 1,602 patients who underwent coronary revascularization had CPVs implanted (1.2%). There were no operative deaths. An attempt was made to evaluate the patency of all grafts with coronary arteriography or ultrafast computed tomographic scans. Fourteen patients were available for patency evaluation. Patency rate in the 14 patients studied at a mean of 7 +/- 2 months (range, 2 to 16 months) were: internal mammary artery, 93% (14/15); saphenous vein graft, 80% (4/5); and CPV, 41% (7/17). The patency of the CPV was significantly less than the patency rate for the saphenous vein and internal mammary artery (p = 0.004). We conclude that the short-term patency rate of CPVs is inferior to that of autologous vessels. Due to its poor patency, we recommend that CPV should only be used when no other autologous conduit is available.

Aged↗
PubMed1992

The developmental patterns of B cell precursors distinguishing between environmental and nonenvironmental forms of phosphocholine.

We have analyzed the developmental patterns of two groups of B cell precursors in nonimmunized BALB/c mice with respect to their relative proportions, absolute frequencies, V gene usage, fine specificity, and avidity for antigen. One group of B cells (group I) secretes antibodies specific for PC and PC-containing bacteria, whereas the other group (group II) produces antibodies recognizing only nonenvironmental PC-protein conjugates. A marked shift in the proportions of group I and group II occurs during ontogeny: while the group I B cells dominate (greater than 85%) the adult antibody repertoire, the group II B cells have equal representation in neonatal mice from Days 1 to 7, and remain as a significant portion until 2 weeks of age. Examination of the absolute frequencies of group I and group II B cells revealed that the frequency of group II B cells remained relatively stable throughout ontogeny, whereas group I B cells expanded rapidly after 7 days of age to predominate in the adult. Genetic analysis indicated that early group I antibodies were encoded by VH and VL genes different from adult group I antibodies which are mostly encoded by a single VH (S107) and VL (V kappa 22) gene combination (the T15 idiotype). On the other hand, early group II antibodies used VH genes comparable to their adult counterparts. The majority of early group I antibodies have lower avidity for PC than adult T15+ antibodies, whereas the avidity of neonatal group II antibodies varies considerably and is comparable with that of the adult group II antibodies. Our results suggest that the ontogeny of phosphocholine-specific B cells may be regulated according to their fine specificity rather than to their avidity or V gene usage.

Age Factors↗
PubMed1992

Nucleotide sequence analysis of 95 kb near the 3' end of the murine T-cell receptor alpha/delta chain locus: strategy and methodology.

The nucleotide sequence of a region at the 3' terminus of the murine T-cell receptor alpha/delta chain locus is presented. This region, which encodes the constant region genes for alpha and delta chain polypeptides and all 50 joining gene segments for the alpha chain polypeptide, spans 94,647 bp and includes more than 50 noncoding sequence elements important for T-cell receptor gene rearrangement and expression. DNA sequencing of this region included complete analysis of two cosmid clones and five additional restriction fragments using a random subcloning approach with various manual and automated sequencing strategies. The automated sequencing strategies hold considerable promise for future large-scale DNA sequencing efforts.

Animals↗
PubMed1992

Mechanism(s) involved in meat mutagen formation and inhibition.

The Maillard reaction, which involves Amadori rearrangement as a key step, also results in sugar fragmentation and free radical formation. The imidazoquinoline meat mutagens (2-amino-3-methylimidazo[4,5-f]-quinoline, or IQ, and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, or MeIQ) are formed from a reaction mixture containing alkylpyridine free radicals and creatinine. The imidazoquinoxaline meat mutagens (2-amino-3,4-dimethylimidazo[4,5-f]-quinoxaline, or MeIQx, and 2-amino-3,4,8-trimethylimidazo[4,5-f]-quinoxaline, or 4,8-DiMeIQx) may be produced by reacting a mixture containing dialkylpyrazine free radicals and creatinine. Two different pathways for free radical formation are proposed. One involves bimolecular ring formation from the enaminol form of the glycoaldehyde alkylimine and is followed by oxidative formation of the free radical. The other pathway involves formation of N,N1-dialkylpyrazinium ions from glyoxal monoalkylimine followed by reduction to produce the free radicals. The respective intermediates (glycoaldehyde alkylimine and glyoxal monoalkylamine) are formed by reacting glycoaldehyde and glyoxal with amino compounds. The glycoaldehyde system reacts faster and produces more free radicals than the glyoxal system. The reactions help to explain the formation of imidazoquinoxaline meat mutagens and their predominance in fried fish and why these mutagens are present in larger quantities in fried ground beef than the imidazoquinoline-type meat mutagens. These two pathways may not be the only mechanisms involved in formation of meat mutagens, but other free radical reactions may also contribute to meat mutagenicity and are mentioned briefly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The effects of fasting and refeeding on liver glycogen synthase and phosphorylase in obese and lean mice.

The responses of hepatic glycogen synthase and phosphorylase to fasting and refeeding were assessed as part of an investigation into possible sites of insulin resistance in gold thioglucose (GTG) obese mice. The active forms glycogen synthase and phosphorylase (synthase I and phosphorylase a) and the total activity of these enzymes were estimated in lean and GTG mice over 48 h of food deprivation, and for 120 min after glucose gavage (1 g/kg wt). In lean mice there was a maximal reduction in hepatic glycogen content after 12 h of starvation and the activity of phosphorylase a decreased from 23.8 +/- 1.9 to 6.8 +/- 0.7 mumol/g protein/min. These changes were accompanied by an increase in the activity of synthase I (from 0.14 +/- 0.01 to 0.46 +/- 0.04 mumol/g protein/min). In obese mice, similar changes in enzyme activity occurred after 48 h of starvation. These changes were accompanied by a significant reduction in the hyperinsulinemia and hyperglycemia of the GTG mice. After glucose gavage in both lean and obese mice, the activity of synthase I further increased over the first 30 min and declined thereafter. The activity of phosphorylase a increased progressively after refeeding. Results from this study suggest that despite increased hepatic glycogen deposition, the responses of glycogen synthase and phosphorylase, in livers of obese mice, to fasting and refeeding are similar to those of control mice even in the presence of insulin resistance.

Animals↗
PubMed1992

Investigation on the carcinogenic effects of coal tar pitch in rat respiratory tract by intratracheal instillations.

The effects of coal tar pitch (CTP) on the tracheobronchial mucosa of Wistar rats were studied. Three groups of animals received 10 weekly intratracheal instillations of CTP at the cumulative doses of 6.48, 136.56 and 200 mg respectively. The control group of rats received 10 weekly intratracheal instillations of charcoal powder at a cumulative dose of 20 mg. The study in which the animals were killed serially revealed that CTP had conspicuous damage on the respiratory system of rats, especially on the bronchiolo-alveolar areas. The lesions induced by CTP ranged from hyperplastic, metaplastic and dysplastic changes to extensive cancers. These lesions were usually multifocal, and were more severe in the rats receiving higher dosages of CTP. The deposition of CTP particles within or adjacent to these lesions could be readily identified. Lung cancers occurred in 12.5% (4/32) and 25% (10/40) of the rats treated with 136.56 and 200 mg of CTP, whereas no tumors were found in control rats and the rats that received 6.48 mg of CTP. The overall cancer incidence significantly related to the cumulative dose of CTP. The histological types of lung cancers consisted of squamous cell carcinomas (10 out of the 14 lung cancers), adenocarcinoma (1/14), and combined squamous and adenocarcinomas (3/14). The development of CTP-induced rat lung cancers appears to derive from the hyperplasias of bronchiolo-alveolar epithelium, and processing stages of squamous metaplasias and/or dysplasias to carcinomas. The present results confirmed the carcinogenic effects of CTP on the respiratory system of rats, and provided experimental evidence for human lung carcinogenesis, particularly in those occupationally exposed to coal tars or tar products.

Adenocarcinoma↗
PubMed1992

Characterization of an Electron Transport Pathway Associated with Glucose and Fructose Respiration in the Intact Chloroplasts of Chlamydomonas reinhardtii and Spinach.

The role of an electron transport pathway associated with aerobic carbohydrate degradation in isolated, intact chloroplasts was evaluated. This was accomplished by monitoring the evolution of (14)CO(2) from darkened spinach (Spinacia oleracea) and Chlamydomonas reinhardtii chloroplasts externally supplied with [(14)C]fructose and [(14)C]glucose, respectively, in the presence of nitrite, oxaloacetate, and conventional electron transport inhibitors. Addition of nitrite or oxaloacetate increased the release of (14)CO(2), but it was shown that O(2) continued to function as a terminal electron acceptor. (14)CO(2) evolution was inhibited up to 30 and 15% in Chlamydomonas and spinach, respectively, by 50 mum rotenone and by amytal, but at 500- to 1000-fold higher concentrations, indicating the involvement of a reduced nicotinamide adenine dinucleotide phosphate-plastoquinone oxidoreductase. (14)CO(2) release from the spinach chloroplast was inhibited 80% by 25 mum 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone. (14)CO(2) release was sensitive to propylgallate, exhibiting approximately 50% inhibition in Chlamydomonas and in spinach chloroplasts of 100 and 250 mum concentrations, respectively. These concentrations were 20- to 50-fold lower than the concentrations of salicylhydroxamic acid (SHAM) required to produce an equivalent sensitivity. Antimycin A (100 mum) inhibited approximately 80 to 90% of (14)CO(2) release from both types of chloroplast. At 75 mum, sodium azide inhibited (14)CO(2) evolution about 50% in Chlamydomonas and 30% in spinach. Sodium azide (100 mm) combined with antimycin A (100 mum) inhibited (14)CO(2) evolution more than 90%. (14)CO(2) release was unaffected by uncouplers. These results are interpreted as evidence for a respiratory electron transport pathway functioning in the darkened, isolated chloroplast. Chloroplast respiration defined as (14)CO(2) release from externally supplied [1-(14)C]glucose can account for at least 10% of the total respiratory capacity (endogenous release of CO(2)) of the Chlamydomonas reinhardtii cell.

Journal Article↗
PubMed1992

Coupling of Carbon Dioxide Fixation to the Oxyhydrogen Reaction in the Isolated Chloroplast of Chlamydomonas reinhardtii.

The oxyhydrogen reaction (the reduction of O(2) to water by H(2)) in the presence of CO(2) was studied in the isolated Chlamydomonas reinhardtii chloroplast by monitoring the rate of (14)CO(2) incorporation into acid-stable products in the dark. The endogenous rate of CO(2) uptake (50-125 nmol/mg chlorophyll per h) was increased about 3- to 4-fold by ATP and additionally when combined with glucose, ribose-5-phosphate, and glycerate-3-phosphate. The rate was diminished 50 to 75%, respectively, when H(2) was replaced by N(2) or by air. Decrease in CO(2) uptake by dl-glyceraldehyde was taken to indicate that the regenerative phase and complete Calvin cycle turnover were involved. Diminution of CO(2) incorporation by rotenone, antimycin A, and 2,5-dibromo-3-methyl-6-isopropanol-p-benzoquinone was attributed to an inhibition of the oxyhydrogen reaction, resulting in an elevated NADPH/NADP ratio. If so, then the diminished CO(2) uptake could have been by "product inhibition" of the carbon metabolic network. Our data are consistent with the proposal (H. Gaffron [1942] J Gen Physiol 26: 241-267) that CO(2) fixation coupled to the oxyhydrogen reaction is dependent to some extent on exchloroplastic metabolism. This support is primarily ATP provided by mitochondrial respiration.

Journal Article↗