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Biomedical subjects

H Zhou

Publications and source records attributed to H Zhou.

At least 343 records · Page 19Linked to original sources
PubMed1999

The multiple roles of conserved arginine 286 of 1-aminocyclopropane-1-carboxylate synthase. Coenzyme binding, substrate binding, and beyond.

A pyridoxal 5'-phosphate (PLP)-dependent enzyme, 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (S-adenosyl-L-Met methylthioadenosine-lyase, EC 4.4.1.14), catalyzes the conversion of S-adenosyl-L-methionine (AdoMet) to ACC. A tomato ACC synthase isozyme (LE-ACS2) with a deletion of 46 amino acids at the C terminus was chosen as the control enzyme for the study of the function of R286 in ACC synthase. R286 of the tomato ACC synthase was mutated to a leucine via site-directed mutagenesis. The ACC synthase mutant R286L was purified using a simplified two-step purification protocol. Circular dichroism (CD) analysis indicated that the overall three-dimensional structure of the mutant was indistinguishable from that of the control enzyme. Fluorescence spectroscopy revealed that the binding affinity of R286L ACC synthase for its cofactor PLP was reduced 20- to 25-fold compared with control. Kinetic analysis of R286L showed that this mutant ACC synthase had a significantly reduced turnover number (k(cat)) of 8.2 x 10(-3) s(-1) and an increased K(m) of 730 microM for AdoMet, leading to an 8,000-fold decrease in overall catalytic efficiency compared with the control enzyme. Thus, R286 of tomato ACC synthase is involved in binding both PLP and AdoMet.

Amino Acid Sequence↗
PubMed1999

Topology and dynamics of the 10 kDa C-terminal domain of DnaK in solution.

Hsp70 molecular chaperones contain three distinct structural domains, a 44 kDa N-terminal ATPase domain, a 17 kDa peptide-binding domain, and a 10 kDa C-terminal domain. The ATPase and peptide binding domains are conserved in sequence and are functionally well characterized. The function of the 10 kDa variable C-terminal domain is less well understood. We have characterized the secondary structure and dynamics of the C-terminal domain from the Escherichia coli Hsp70, DnaK, in solution by high-resolution NMR. The domain was shown to be comprised of a rigid structure consisting of four helices and a flexible C-terminal subdomain of approximately 33 amino acids. The mobility of the flexible region is maintained in the context of the full-length protein and does not appear to be modulated by the nucleotide state. The flexibility of this region appears to be a conserved feature of Hsp70 architecture and may have important functional implications. We also developed a method to analyze 15N nuclear spin relaxation data, which allows us to extract amide bond vector directions relative to a unique diffusion axis. The extracted angles and rotational correlation times indicate that the helices form an elongated, bundle-like structure in solution.

Amino Acid Sequence↗
PubMed1999

A random effects model for multivariate failure time data from multicenter clinical trials.

A random effects model for analyzing multivariate failure time data is proposed. The work is motivated by the need for assessing the mean treatment effect in a multicenter clinical trial study, assuming that the centers are a random sample from an underlying population. An estimating equation for the mean hazard ratio parameter is proposed. The proposed estimator is shown to be consistent and asymptotically normally distributed. A variance estimator, based on large sample theory, is proposed. Simulation results indicate that the proposed estimator performs well in finite samples. The proposed variance estimator effectively corrects the bias of the naive variance estimator, which assumes independence of individuals within a group. The methodology is illustrated with a clinical trial data set from the Studies of Left Ventricular Dysfunction. This shows that the variability of the treatment effect is higher than found by means of simpler models.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Cross-sectional study of gastric ulcers of the squamous mucosa in thoroughbred racehorses.

Although gastric ulcers have been identified relatively frequently in racing Thoroughbreds, there have been no large scale studies to determine their effect on health and performance. Two hundred and two Thoroughbred horses in active race training were selected by the attending veterinarians for gastro-endoscopic examination. Images of the stomach mucosa were stored in a digitised format for subsequent evaluation. The number of ulcers and a score of severity were determined. Gastric ulceration of the squamous mucosa was identified in 82% of horses. Seventy-three (39%) horses displayed clinical signs consistent with gastric ulceration. Increasing Furr and Murray Score was associated with poor hair coat (P = 0.03), colic (P = 0.03), and increasing serum creatinine concentration (P = 0.029). There were no associations between haematology and serum biochemistry values (other than serum alkaline phosphatase concentration and serum creatinine concentration) and gastric ulceration. Our study confirmed the relatively high incidence of gastric ulceration in Thoroughbred horses involved in active race training. Gastric ulceration is a potential, but rare, cause of overt colic, but may produce more subtle detrimental effects on a horse's condition. It is concluded that the diagnosis of gastric ulceration should be based on an endoscopic examination of the stomach, although future studies are required to elucidate further the aetiology and clinical significance of gastric ulceration.

Animals↗
PubMed1999

Seven novel methylation guide small nucleolar RNAs are processed from a common polycistronic transcript by Rat1p and RNase III in yeast.

Through a computer search of the genome of the yeast Saccharomyces cerevisiae, the coding sequences of seven different box C/D antisense small nucleolar RNAs (snoRNAs) with the structural hallmarks of guides for rRNA ribose methylation have been detected clustered over a 1.4-kb tract in an inter-open reading frame region of chromosome XIII. The corresponding snoRNAs have been positively identified in yeast cells. Disruption of the nonessential snoRNA gene cluster specifically suppressed the seven cognate rRNA ribose methylations but did not result in any growth delay under the conditions of yeast culture tested. The seven snoRNAs are processed from a common polycistronic transcript synthesized from an independent promoter, similar to some plant snoRNAs but in marked contrast with their vertebrate functional homologues processed from pre-mRNA introns containing a single snoRNA. Processing of the polycistronic precursor requires nucleases also involved in rRNA processing, i.e., Rnt1p and Rat1p. After disruption of the RNT1 gene, the yeast ortholog of bacterial RNase III, production of the seven mature snoRNAs was abolished, while the polycistronic snoRNA precursor accumulated. In cells lacking functional Rat1p, an exonuclease involved in the processing of both pre-rRNA and intron-encoded snoRNAs, several processing intermediates of the polycistronic precursor accumulated. This allowed for the mapping in the precursor of the presumptive Rnt1p endonucleolytic cuts which provide entry sites for subsequent exonucleolytic trimming of the pre-snoRNAs. In line with known properties of double-stranded RNA-specific RNase III, pairs of Rnt1p cuts map next to each other on opposite strands of long double-helical stems in the secondary structure predicted for the polycistronic snoRNA precursor.

Base Sequence↗
PubMed1999

Lack of effect of erythromycin and ketoconazole on the pharmacokinetics and pharmacodynamics of steady-state intranasal levocabastine.

The single-dose effects of the cytochrome P-450 inhibitors erythromycin and ketoconazole on the steady-state pharmacokinetics and electrocardiographic repolarization pharmacodynamics of intranasal levocabastine, a potent and selective H1-receptor antagonist, were evaluated in healthy young male subjects. Two randomized, open-label, placebo-controlled, two-way crossover studies were performed. Levocabastine nasal spray was administered as two sprays per nostril (0.05 mg/spray) twice daily (for a total daily dose of 0.4 mg) for 6 days. On Day 7, a single dose of 0.2 mg was administered followed immediately by a single dose of either oral placebo, erythromycin 333 mg, or ketoconazole 200 mg. In all treatment groups, levocabastine was rapidly absorbed, with peak plasma concentrations reached at approximately 3 hours in the erythromycin study and 2.8 hours in the ketoconazole study. The mean terminal half-life was approximately 45 and 44 hours, respectively. In both studies, mean steady-state plasma concentrations and pharmacokinetics of levocabastine following the single doses of erythromycin or ketoconazole were not significantly different from corresponding values seen with the concomitant administration of the placebo. No clinically significant mean changes from baseline in QT or QTc (QT corrected for heart rate) intervals occurred in any of the treatment groups, and none of the subjects in either study experienced abnormally prolonged QTc intervals. Intranasal levocabastine was well tolerated, with no difference in the incidence of adverse events between treatment groups in either study; adverse events were generally mild in severity. Since levocabastine undergoes only minimal hepatic metabolism and is not a substrate for or an inhibitor of cytochrome P-450, the likelihood of systemic drug interactions with drugs affecting the cytochrome P-450 system is minimal.

Administration, Intranasal↗
PubMed1999

Effect of meal timing not critical for the pharmacokinetics of tegaserod (HTF 919).

This study assessed the pharmacokinetic profiles of administering tegaserod (HTF 919) at different time intervals with respect to a meal. It was a randomized, open-label, two-phase, five-period crossover study. In the first phase, 18 healthy subjects received a single 12 mg oral dose of tegaserod administered either 30 or 15 minutes prior to the start of the 600-calorie, fat-rich breakfast. In the second phase, subjects received a single 12 mg oral dose of tegaserod 1 minute before, 2.5 hours after the start of meal, or with a continued 4-hour postdose fast. Safety assessment and plasma samples for the determination of drug concentration were obtained for 24 hours postdose. Noncompartmental analysis results indicated that the AUC of tegaserod was reduced by almost half under fed conditions compared to the fasted condition. Exploratory analyses were implemented to further investigate the absorption characteristics of tegaserod under different fed conditions. A numerical deconvolution approach was used to obtain the tegaserod oral absorption versus time profiles under both fasted and fed conditions. The tegaserod oral absorption versus time profiles were then fitted by NONMEM to a model containing two absorption phases. Based on the absorption analyses, we found that the reduction in the bioavailability of tegaserod under fed conditions was primarily due to a decrease in the extent of absorption and less so to a decrease in the absorption rate(s). Therefore, although the timing of administration of food does not appear to significantly alter the pharmacokinetics of tegaserod, the administration of food reduces the AUC by approximately 50%.

Adult↗
PubMed1999

The effect of Oren-gedoku-to on experimental colitis in rats.

In Japan and China, Oren-gedoku-to (a complex mixture of ingredients derived from plants) has been used as a herbal medicine in the treatment of inflammatory and ulcerative diseases. In other countries salicylazosulfapyridine has been used to treat inflammatory bowel disease. In this study, we have compared the effect of Oren-gedoku-to with salicylazosulfapyridine on trinitrobenzene-sulphonic acid-induced colonic damage in rats, a model representative of ulcerative colitis and Crohn's disease in man. Oren-gedoku-to was administered orally for one or two weeks over a range of doses. Tissue damage scores, body weight, spleen weight, colon wet weight and colon wall thickness were measured, and colonic tissue levels of interleukin-8 (IL-8), leukotriene B4 (LTB4), prostaglandin E2 (PGE2), and myeloperoxidase activity were examined. The results indicated that Oren-gedoku-to was effective in the treatment of inflammatory bowel disease in the rat model. Histological observation showed a quicker healing process of the lesions, and a reduction of inflammatory cell infiltration following administration of Oren-gedoku-to. The precise mechanism of action for Oren-gedoku-to is still unclear; however, the reduction of IL-8, LTB4, and PGE2 observed suggests that the mechanism may be different from salicylazosulfapyridine (which has no effect on IL-8). There may be a potential benefit in offering combination therapy for the treatment of inflammatory bowel disease.

Animals↗
PubMed1999

Treatment delay and reliance on private physicians among patients with sexually transmitted diseases in China.

We examined health-care seeking practices among patients with sexually transmitted diseases (STDs) in south China. In 1995, we recruited a consecutive sample of 939 STD patients attending the STD clinics of the Municipal STD Control Centers of Guangzhou and Shenzhen, 'special economic zones' near Hong Kong. Attending physicians interviewed patients face-to-face using a standard survey questionnaire. Twenty-seven per cent of all subjects had sought treatment elsewhere for their presenting complaints, before visiting a study clinic. The main sources of prior treatment were private physicians followed by public clinics and drugstores. Women were more likely than men to delay in presenting their current symptoms to a study clinic (32% vs 25%, P=0.046). Factors associated with treatment delay differed by gender. Among men, seeking prior treatment from private physicians (OR=3.31; 95% CI=1.70, 6.43), having no urethral discharge (OR=4.00; 95% CI=2.33, 6.85), having engaged in sex trade (OR=1.64; 95% CI=1.03, 2.63), or being a resident in Shenzhen (OR=1.80; 95% CI=1.12, 2.89) were more likely to delay seeking treatment. Among women, only living in Shenzhen (OR=2.86; 95% CI=1.56, 5.25) was associated with treatment delay. Promotion of appropriate health-seeking behaviours and better management of STDs must be a top priority to slow a rapid spread of STD/HIV in China. Health education, improvement of STD care in the public and private sectors, and regulations of unauthorized private physicians, may help with STD control and HIV prevention.

Adult↗
PubMed1999

Radiological factors influencing femoral and acetabular failure in cemented Charnley total hip arthroplasties.

We have made a retrospective review of 185 cemented Charnley total hip arthroplasties performed between 1970 and 1974 to determine the relationships between radiological variables and failure of the femoral and acetabular components. We measured the acetabular wear, the orientation of the cup, the thickness and consistency of acetabular and femoral cement mantles, radiolucency and femoral alignment. The mean follow-up was for 11.7 years. Femoral loosening was demonstrable radiologically in 15 hips (8.1%), ten (5.4%) of which were revised during the period of follow-up. Only when the first postoperative radiograph showed a thin cement mantle in Gruen zone 5 was there a significant association with failure of the femoral component. There were 12 loose acetabular components (6.5%), nine (4.8%) of which were revised. When the initial radiograph after operation showed radiolucency in DeLee and Charnley zone 1, the incidence of acetabular loosening was 28.21%. If such radiolucency was not present, the incidence of acetabular loosening was only 0.69%. Our findings emphasise the importance of careful cementing.

Acetabulum↗
PubMed1999

The zymogen prothrombin stimulates cell locomotion and calcium influx in murine osteosarcoma cells by different mechanism from thrombin.

The coagulation system plays a role in tumor invasion and metastasis. Prothrombin was previously found to stimulate the motility of melanoma cells. We compared the effect of prothrombin and thrombin on cell motility, calcium influx and actin stress filament contraction in highly metastatic osteosarcoma LM8 cells. Prothrombin and thrombin stimulated chemotaxis and chemokinesis of LM8 cells in a dose-dependent manner. Calcium influx was significantly increased after stimulation with thrombin and prothrombin. Thrombin and prothrombin markedly stimulated actin contraction in LM8 cells. Hirudin inhibited the effects of thrombin but not those of prothrombin. Prothrombin appears to stimulate cell locomotion, actin contraction, calcium influx in LM8 cells by different mechanism from thrombin.

Actins↗
PubMed1999

Kinetics of thermal inactivation of penaeus penicillatus acid phosphatase

The kinetics of thermal inactivation of Penaeus penicillatus acid phosphatase have been studied using a kinetic method related to the substrate reaction during irreversible inhibition of the enzyme activity as previously described by Tsou (Adv. Enzymol. Relat. Areas Mol. Biol. (1988) 61, 381-436). The kinetics of thermal inactivation of the enzyme show that the reaction is irreversible. The microscopic rate constants were determined for thermal inactivation of free enzyme and the enzyme--substrate complex. The results show that the presence of substrate has a significant protective effect against thermal inactivation of the enzyme.

Journal Article↗
PubMed1999

Antagonistic effects of berbamine on [Ca2+]i mobilization by KCl, norepinephrine, and caffeine in newborn rat cardiomyocytes.

AIM: To study the effects of berbamine (Ber) on intracellular calcium concentration ([Ca2+]i) mobilized by KCl depolarization, norepinephrine (NE), and caffeine. METHODS: [Ca2+]i was measured with fluorescent intensity (FI) by confocal microscope in single cultured cardiomyocytes of newborn rats loaded with Fluo 3-AM 2 mumol.L-1. RESULTS: FI value of [Ca2+]i in control level was 248 +/- 70 in the presence of extracellular calcium 1.5 mmol.L-1 and was not changed by Ber 3-30 mumol.L-1. KCl (60 mmol.L-1)- and NE (30 mumol.L-1)-induced [Ca2+]i mobilizations were inhibited (P < 0.01) by Ber 30 mumol.L-1, similar to that of verapamil (Ver). The inhibitory effect of Ber on [Ca2+]i induced by KCl was further increased (P < 0.05) in the presence of egtazic acid 3 mmol.L-1, but that on [Ca2+]i induced by NE was not changed. The [Ca2+]i mobilized by caffeine 80 and 160 mumol.L-1 in D-Hanks' solution was not affected (P > 0.05) by Ber and Ver. CONCLUSION: Ber possessed the antagonistic effects on [Ca2+]i increases via voltage-dependent Ca2+ channel and receptor-operated Ca2+ channel in newborn rat cardiomyocytes, but without effect on intracellular Ca2+ release.

Alkaloids↗
PubMed1999

Patellar complications (total knee arthroplasty). Effect of lateral release and thickness.

One thousand, one hundred forty-six Anatomic Graduated Component total knee arthroplasties performed between 1987 and 1989 were used to investigate the effects of patellar thickness alone or coupled with lateral retinacular release on initial patellar complications and maximal flexion. Lateral release was found not to be statistically significant regarding radiolucency, patellar prosthesis loosening, or an increase or decrease in flexion. However, total knee arthroplasties in which a lateral release was done, which either saved the superior lateral genicular artery or sacrificed the superior lateral genicular artery, were found to increase the incidence of initial patellar fractures and/or loosening (complications within 1 year) when compared with total knee arthroplasties in which a lateral release was not performed. There was no statistical difference in failure rates regarding fractures and/or loosening of the patella between lateral releases in which the superior lateral genicular artery was saved and the lateral releases in which the superior lateral genicular artery was sacrificed. A difference in postoperative patellar thickness compared with preoperative patellar thickness was found not to be significant to initial patellar fracture and/or loosening, patellar fracture alone, patellar loosening alone, radiolucency, the need for a lateral release, or to an increase or decrease in flexion. Lateral release and patellar thickness had no significant effect on patellar fracture and/or loosening.

Adult↗
PubMed1999

Cytosolic-Ca2+ and coxsackievirus B3-induced apoptosis in cultured cardiomyocytes of rats.

AIM: To explore the role of cytosolic free calcium ([Ca2+]i) in apoptosis induced by coxsackievirus B3 (CVB3) in cultured cardiomyocytes of rats. METHODS: Primary cultured cardiomyocyte was prepared from Wistar rats ages 2-3 d. The apoptosis in cardiomyocyte was determined by terminated deoxynucleotide transferase directed d-UTP nick and end labeling (TUNEL) method, and the apoptosis was observed under a transmission electron microscope. [Ca2+]i in single cardiomyocyte loaded with Fluo 3-AM was measured by confocal microsorope. RESULTS: (1) The concentration of CVB3 in the medium reached the peak at 24 h after CVB3 infection. (2) The apoptotic cells were not found in CVB3-infected cardiomyocyte in first 10 h, but amounted to 5% at 17 h, 60% at 24 h, and 90% at 36 h. (3) The peak value of [Ca2+]i elevation reached at 17 h after CVB3 infection (P < 0.01). (4) The characteristics of apoptosis was also seen by transmission electron microscope. CONCLUSION: CVB3 induced the apoptosis in cultured cardiomyocyte, and [Ca2+]i mobilization was involved in the signal transduction process in apoptosis cells, and played an important role especially in the early stage of apoptosis induced by CVB3.

Animals↗
PubMed1999

Effects of berbamine on ATP-induced [Ca2+]i mobilization in cultured vascular smooth muscle cells and cardiomyocytes.

AIM: To study the effects of berbamine (Ber) on [Ca2+]i homeostasis induced by adenosine triphosphate (ATP) in vascular smooth muscle cells (VSMC) of rabbits and cardiomyocytes of rats. METHODS: Both cell types were cultured and loaded with Fura 3-AM. [Ca2+]i was measured by fluorescent intensity (FI) in each cell with confocal microscopy. RESULTS: (1) ATP 30 mumol.L-1 elevated [Ca2+]i in VSMC and cardiomyocytes, FI values reached 660 +/- 258 and 1058 +/- 252 from 250 +/- 84 and 218 +/- 76 at 19 s +/- 5 s and 11.8 s +/- 2.4 s, but FI in nucleus was not changed in VSMC. (2) Ber 30 mumol.L-1 did not affect the resting FI in both cell types, but prolonged the time to peak (P < 0.01) and reduced the FI elevated by ATP (P < 0.01), but not completely inhibited even at 100 mumol.L-1. (3) In D-Hanks' solution or in the presence of egtazic acid (EGTA) 3 mmol.L-1, the inhibitory effect of Ber was not seen (P > 0.05). (4) All effects of Ber on ATP-induced [Ca2+]i mobilization were similar to those of Ver 10 mumol.L-1. CONCLUSION: In VSMC and cardiomyocytes, ATP-induced CA2+ influx was inhibited by Ber and Ver, while the Ca2+ release was not.

Alkaloids↗