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Biomedical subjects

H G Chen

Publications and source records attributed to H G Chen.

18 recordsLinked to original sources
PubMed2004

In vitro mutagenesis of Xanthomonas campestris alpha-amylase gene by partially replacing deoxythymidine triphosphate with 5-bromo-2'-deoxyuridine-5'-triphosphate using a PCR technique.

Three mutants of the wild type alpha-amylase gene from Xanthomonas campestris pv. campestris 8004 were obtained using a PCR technique in which deoxythymidine triphosphate (dTTP) was partially replaced by 5-bromo-2'-deoxyuridine-5'-triphosphate (BrdUTP), at an optimal dTTP:BrdUTP ratio of 1000:1. Of thre three mutants that were obtained and which were sequenced, one mutant with 40 times higher activity than the wild type alpha-amylase gene product was obtained by using primary PCR products as a template for a second PCR reaction.

Cloning, Molecular↗
PubMed2001

A baseline study on the importance of bovines for human Schistosoma japonicum infection around Poyang Lake, China.

We hypothesize that bovine infections are responsible for the persistence of human schistosomiasis transmission in the Yangtze marshlands of China. To test this hypothesis, we are carrying out a comparative intervention among four administrative villages in the Poyang Lake region, Jiangxi Province, two of which are experimental and two are control. The primary design involves treating, at the onset of the study, all the inhabitants in all four villages with praziquantel and all the bovines in two villages (the experimental or intervention villages). Following treatment, rates of reinfection in people of all villages, and in bovines in the experimental villages, will be assessed as will the ongoing prevalence of infection in bovines in the control villages. Before treatment, the prevalence and intensity of infection among humans and bovines was ascertained in the four villages. Our study design and baseline information are presented here, along with a description of the ecology of the study villages.

Adolescent↗
PubMed2000

Phosphate prodrugs of PD154075.

In the preparation of phosphate prodrugs of PD154075, several strategies of linking a phosphate group to the indole moiety were studied. A novel linker, p-hydroxymethylbenzoyloxymethoxycarbonyl, was discovered to provide the phosphate prodrug of PD154075 (compound 9) with significantly increased aqueous solubility, sufficient stability in aqueous solution and good bio-reconversion in vivo.

Animals↗
PubMed2000

Arterial baroreceptors control plasma vasopressin responses to graded hypotension in conscious dogs.

We studied the role of cardiac and arterial baroreceptors in the reflex control of arginine vasopressin (AVP) and renin secretion during graded hypotension in conscious dogs. The dogs were prepared with Silastic cuffs on the thoracic inferior vena cava and catheters in the pericardial space. Each experiment consisted of a control period followed by four periods of inferior vena caval constriction, during which mean arterial pressure (MAP) was reduced in increments of approximately 10 mmHg. The hormonal responses were measured in five dogs under four treatment conditions: 1) intact, 2) acute cardiac denervation (CD) by intrapericardial infusion of procaine, 3) after sinoaortic denervation (SAD), and 4) during combined SAD+CD. The individual slopes relating MAP to plasma AVP and plasma renin activity (PRA) were used to compare the treatment effects using a 2 x 2 factorial analysis. There was a significant (P < 0.01) effect of SAD on the slope relating plasma AVP to MAP but no effect of CD and no SAD x CD interaction. In contrast, the slope relating PRA and MAP was increased (P < 0.05) by SAD but was not affected by CD. These results support the hypothesis that stimulation of AVP secretion in response to graded hypotension is primarily driven by unloading arterial baroreceptors in the dog.

Animals↗
PubMed1995

Stereoselective synthesis of Xaa psi[CH2CH(OH)]Yaa dipeptidomimetics and their inclusion in HIV-1 protease inhibitors.

Two stereoselective syntheses of a new pseudodipeptide isostere, the right-hand hydroxyethylene dipeptidomimetic (Xaa psi[CH2CH(OH)]Yaa), are presented. In one method readily available amino acids are used as starting materials for Evans chiral aldol condensation chemistry. The second method relies on the synthesis of an anti-aldol product for the hydroxyethylene isostere via an E-selective ethyl hydrocinnamate enolization, and thus allows for the synthesis of isosteres having side chains other than those available from amino acids. Both methods are illustrated by the chiral synthesis of Boc-Phe psi[CH2CH(OH)]Phe. Two diastereomers, (S,S,R) and (S,R,R), are incorporated into an HIV-1 protease inhibitor template which yields potent inhibitors of HIV-1 protease when the pseudodipeptide isostere is Phe psi[CH(OH)CH2]Phe or Phe psi[CH(OH)CH(OH)]Phe. The resulting Phe psi[CH2CH(OH)]Phe-containing inhibitors possess modest potency.

Dipeptides↗
PubMed1994

[Staining test with methylene blue during resection of bladder cancer in 30 patients].

From November 1991 to March 1993, staining test with methylene blue was applied in 30 patients with the bladder cancer during operation. Twelve patients (40%) showed positive results, and 27 specimens were obtained from the stained areas. Histological examination proved that they were carcinoma in situ (11), transitional cell carcinoma (7), squamous cell carcinoma (4), dysplasia (3), chronic cystitis (1), and normal mucosa (1). The positive rate of histological results was 96.3%. 21 specimens from the unstained areas showed negative results. Six (33%) of 18 patients with single tumor and 6 (50%) of 12 patients with multiple tumor were positively stained. Follow-up from 10 to 26 months showed one patient (3.3%) had recurrence after 8 months.

Adult↗
PubMed1993

Effects of high-energy shock waves on testes of Wistar rats.

The effects of high-energy shock wave (HESW) on testes are still unknown. We investigated Wistar rats at 3 months of age for morphologic and functional changes in the testes and in serum follicle-stimulating hormone (FSH), progesterone (Prog), and testosterone (T). In an initial study, 12 rats received 1000 shocks at 19 kV directed at their testes using the JDPN-IV lithotripter. Two animals were sacrificed, and their testes were step-sectioned for light and electron microscopic examination on the operation day and on postoperation days one, two, four, eight, and sixty. There was angiectasis and congestion (58%) and focal hemorrhage (42%) in the testicular tissue, as well as mitochondrial swelling, reduction or disappearance of mitochondrial cristae (42%), and degranulation of the rough endoplasmic reticulum (33%) in spermatocytes. In the definitive study, groups of 10 rats were exposed to the same power index directed at their testes. One week after this exposure in Group 1 and at 3 and 6 weeks in Group 2, the animals were allowed to mate (one male paired with two females). There was no statistically significant difference in pregnancy rate or fetal number and weight in the female rats mated with the two groups of treated males at 3 weeks' gestation or in serum FSH, Prog, and T, or compared with the control group. Although there were temporary histologic changes in testicular tissue, the rat testes appeared to be functionally resistant to the shock wave energy levels used in this experiment.

Animals↗
PubMed1993

The adrenocorticotropic hormone and arginine vasopressin responses to hypercapnia in fetal and maternal sheep.

Previous studies have demonstrated that fetal adrenocorticotropic hormone (ACTH) and arginine vasopressin (AVP) are increased during periods of acidemia produced by infusion of acid intravenously or by acidemia secondary to hypovolemia. The purpose of this study was to quantify ACTH and AVP responses to hypercapnic acidemia and to test the role of the peripheral chemoreceptors in the control of these responses. Chronically catheterized fetal sheep were subjected to carotid sinus denervation and bilateral vagotomy or were studied intact. At least 5 days after surgery, fetuses were exposed to a 60-min period of normocapnia or hypercapnia, delivered via a polyethylene bag containing 5-8% CO2 in 21% O2 fitted over the head of the pregnant ewe. Hypercapnia significantly increased fetal arterial PCO2 to 55.2 +/- 1.8 and 55.9 +/- 2.2 mmHg and decreased arterial pH to 7.257 +/- 0.011 and 7.281 +/- 0.010 in intact and denervated fetuses, respectively. Fetal mean arterial blood pressure was decreased slightly in the denervated fetuses during hypercapnia. Fetal plasma AVP was increased in both groups equally, and plasma ACTH and cortisol were increased in the denervated fetuses only. Fetal heart rate was increased significantly in intact but not denervated fetuses. We conclude that respiratory acidemia is a mild stimulus to AVP secretion and that this response is not attenuated by peripheral chemodenervation.

Adrenocorticotropic Hormone↗
PubMed1992

Reflex control of fetal arterial pressure and hormonal responses to slow hemorrhage.

Late-gestation fetal sheep respond to slow hemorrhage with increases in plasma concentrations of adrenocorticotropic hormone (ACTH), hydrocortisone, arginine vasopressin (AVP), and plasma renin activity (PRA) that correlate to the acidemia and hypercapnia also produced by hemorrhage. This study was designed to investigate the role of peripheral chemoreceptors in the mediation of these responses. Chronically catheterized fetal sheep were left intact or were subjected to bilateral section of cervical vagosympathetic trunks and carotid sinus nerves. At least 5 days after surgical preparation (between 121 and 138 days of gestation) fetuses were bled at a rate of 11 ml/10 min for 2 h. Denervated fetuses were studied with or without simultaneous infusion of phenylephrine. Denervation exaggerated the decrease in mean arterial pressure and arterial pH and the increase in arterial PCO2 during hemorrhage. Infusion of phenylephrine in the denervated fetuses prevented the decrease in blood pressure and reduced the magnitudes of changes in blood gases. Fetal plasma ACTH, hydrocortisone, and PRA responses to the hemorrhage were exaggerated in the denervated fetuses (not infused with phenylephrine) compared with the intact fetuses. Phenylephrine infusion attenuated the ACTH response and inhibited the AVP response but did not alter the PRA response. We conclude that the sectioned fibers are important for the maintenance of blood pressure and blood gases during hemorrhage and that the PRA, AVP, and ACTH responses to slow hemorrhage are not mediated by peripheral chemoreceptors.

Animals↗
PubMed1991

[Study on isoenzymes of Paragonimus iloktsuenensis and Paragonimus westermani by isoelectric focusing].

The isoenzyme patterns of Paragonimus iloktsuenesis and P. westermani were studied by isoelectric focusing on polyacrylamide gels for PGM, MDH, HK, ME, PO and ACP. Interspecific differences were apparent as shown by the isoenzyme profiles of these enzymes examined. MDH was polymorphic with 2 recognizable phenotypes, designated common type and variant type respectively, in P. i. and with 3 phenotypes, designated MDH1, MDH2 and MDH1-2 respectively, in P. w. The result showed that the two species could be distinguished one from another by such species-specific band patterns of isoenzymes. This suggests that P. w. and P. i. have undergone genetically divergent development and P. i. can be regarded as a valid species different from P. w. In the light of MDH polymorphism, some implications of isoenzyme analysis on taxonomy of the genus Paragonimus were discussed.

Animals↗
PubMed1989

Evaluation of biodegradable poly(lactide) pellets prepared by direct compression.

Biodegradable pellets intended for either parenteral or oral use were successfully prepared from low molecular weight poly(DL-lactide) (low MW PLA, MW' = 2000) or a relatively high molecular weight poly(L-lactide) (L-PLA, MW = 215,000) sample by a simple direct compression technique without the use of heat or organic solvents. The energy imparted during the compression step caused fusion of the low MW PLA particles. Pellets prepared from low MW PLA swelled considerably before eroding in pH 7.4 buffer, but acted as an enteric matrix in 0.1 M HCl. This was attributed to the high carboxyl endgroup:polymer chain ratio which increased with a decrease in molecular weight. Interactions between salts of basic drugs (quinidine sulfate or propranolol hydrochloride) and the polymeric carboxyl endgroups caused retardation in the drug release from low MW PLA pellets. The drug release from L-PLA pellets was independent of the pH of the dissolution media and drug-polymer interactions were absent. The drug release could be increased by admixing sodium chloride prior to compression, or reduced by dipping the pellets into methylene chloride for a short period of time.

Calorimetry, Differential Scanning↗
PubMed1989

A novel approach to the oral delivery of micro- or nanoparticles.

A novel oral multiple-unit dosage form which overcame many of the problems commonly observed during the compression of microparticles into tablets was developed in this study. Micro- or nanoparticles were entrapped in beads formed by ionotropic gelation of the charged polysaccharide, chitosan or sodium alginate, in solutions of the counterion, tripolyphosphate (TPP) or calcium chloride (CaCl2), respectively. The described technique did not change the physical properties of the microparticles, and it allowed a high microparticle loading (up to 98%). The ionic character of the polymers allowed pH-dependent release of the microparticles. Chitosan beads disintegrated and released the microparticles in 0.1 N HCl, while calcium alginate beads stayed intact in 0.1 N HCl but rapidly disintegrated in simulated intestinal fluids. Coating the calcium alginate beads with cellulose acetate phthalate resulted in an enteric drug delivery system. Scanning electron microscopy and dissolution and disintegration tests were used to characterize the microparticle-containing beads. The disintegration time of the beads was studied as a function of the solution viscosity of the polysaccharide, gelation time, counterion concentration, and method of drying.

Alginates↗
PubMed1989

Acidemia stimulates ACTH, vasopressin, and heart rate responses in fetal sheep.

Adrenocorticotropic hormone (ACTH), arginine vasopressin (AVP), and renin responses to hemorrhage are highly correlated to the hemorrhage-induced decreases in arterial pH. The present study was designed to test the responses of these three systems to acute fetal acidemia, produced by intravenous infusion of H+. HCl was infused into chronically catheterized fetal sheep at rates of 0.02 (n = 5), 0.10 (n = 6), and 0.50 (n = 5) meq/min. Infusions at rates of 0.10 and 0.50 meq/min significantly decreased fetal arterial pH and increased arterial PCO2. Fetal heart rate and plasma concentrations of ACTH, cortisol, and AVP were significantly increased during infusion of HCl at 0.5 meq/min. Neither fetal plasma renin activity nor fetal arterial blood pressure was significantly altered by any of the infusions. The results of these experiments suggest that fetal ACTH, AVP, and heart rate are stimulated by decreases in arterial pH and/or increases in arterial PCO2. We speculate that these responses are chemoreceptor mediated, although we cannot distinguish the apparent relative roles of peripheral and central chemoreceptors on the basis of the present study.

Acidosis↗
PubMed1989

Role of vagosympathetic fibers in the control of adrenocorticotropic hormone, vasopressin, and renin responses to hemorrhage in fetal sheep.

Hemorrhage stimulates endocrine and cardiovascular reflex responses that are appropriate for returning blood volume and pressure to prehemorrhage levels. Fetal sheep respond to hemorrhage with increases in plasma adrenocorticotropic hormone (ACTH), cortisol, and vasopressin concentrations and plasma renin activity, but little is known about the afferent limb of the reflex(es) controlling these responses. Fetal sheep between 128 and 133 days' gestation were chronically prepared with vascular catheters. Five fetal sheep were subjected to bilateral section of the cervical vagosympathetic trunks; six fetal sheep were not vagotomized. Four to six days after surgery, the fetuses were subjected to withdrawal of 10 ml of blood every 10 minutes for 2 hours (130 ml total). Vagotomized fetal sheep responded to the hemorrhage with a greater decrease in central venous pressure than the intact fetuses and a slower restitution of fluid to the vascular space (estimated to be 17% of the hemorrhage volume in 2 hours) than the intact fetuses (estimated to be 28% of the hemorrhage volume in 2 hours). Both groups of fetuses, however, responded to the hemorrhage with increases in fetal plasma ACTH, cortisol, and vasopressin concentrations and plasma renin activity that were not significantly different. A posteriori analysis of the data by correlation analysis revealed that the fetal ACTH, vasopressin, and renin responses to the hemorrhage were more highly correlated to the changes in fetal arterial pH than to changes in fetal mean arterial pressure or central venous pressure. The results suggest that the ACTH, vasopressin, and renin responses to hemorrhage in the fetus be mediated by chemoreceptors, not by cardiovascular mechanoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1988

Preparation of biodegradable poly(+/-)lactide microparticles using a spray-drying technique.

Drug containing biodegradable poly(+/-)lactide microparticles were prepared by using a spray-drying technique. Formulations containing model drugs in either a dissolved (progesterone) or dispersed state (theophylline) were spray-dried. The spray-drying method was less dependent on the solubility characteristics of the drug when compared with traditional microencapsulation techniques such as phase separation or solvent evaporation techniques. Differential scanning calorimetry and scanning electron microscopy were used to characterize the microparticles. The drug release profiles were characterized by a rapid release phase (burst effect) followed by a slow release phase, the extent of each phase being dependent on the drug loading.

Biodegradation, Environmental↗
PubMed1981

Effect of renal dysfunction in dogs on the disposition and marrow toxicity of melphalan.

The effect of renal failure on melphalan pharmacology and toxicity has been poorly understood. Such information is of interest because melphalan is the most commonly used anticancer drug in the treatment of multiple myeloma, which is frequently associated with renal failure. We have studied the disposition and marrow toxicity of parenteral melphalan in dogs before and after induction of renal failure with subtotal nephrectomy. The surgical procedure decreased the creatinine clearance by an average of 62% (P = 0.001). The lowest neutrophil counts following i.v. melphalan (1 mg/kg) averaged 4.9 x 10(3)/mm3 pre-nephrectomy and 0.9 x 10(3)/mm3 post-nephrectomy, respectively (P = 0.002). The mean lowest recorded platelet counts after melphalan (1 mg/kg) were 115 x 10(3)/mm3 in the pre-nephrectomized dogs, and 9.7 x 10(3/mm3 in those who had been nephrectomized (P = 0.002). Following nephrectomy, i.v. melphalan's terminal-phase plasma half-life and renal clearance were both raised (P = 0.02) to 75% over pre-nephrectomy values. These studies show that i.v. melphalan-induced myelosuppression is markedly increased and its plasma elimination and renal clearance significantly decreased in the presence of renal dysfunction in dogs. These data suggest that parenteral melphalan's starting dose be decreased by at least 50% when used in myeloma patients with renal failure.

Acute Kidney Injury↗