Search PubMed⌕ Search

Biomedical subjects

Z Zhou

Publications and source records attributed to Z Zhou.

At least 217 records · Page 12Linked to original sources
PubMed1999

Studies of phospholipid hydration by high-resolution magic-angle spinning nuclear magnetic resonance.

A sample preparation method using spherical glass ampoules has been used to achieve 1.5-Hz resolution in 1H magic-angle spinning (MAS) nuclear magnetic resonance (NMR) spectra of aqueous multilamellar dispersions of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), serving to differentiate between slowly exchanging interlamellar and bulk water and to reveal new molecular-level information about hydration phenomena in these model biological membranes. The average numbers of interlamellar water molecules in multilamellar vesicles (MLVs) of DOPC and POPC were found to be 37.5 +/- 1 and 37.2 +/- 1, respectively, at a spinning speed of 3 kHz. Even at speeds as high as 9 kHz, the number of interlamellar waters remained as high as 31, arguing against dehydration effects for DOPC and POPC. Both homonuclear and heteronuclear nuclear Overhauser enhancement spectroscopy (NOESY and HOESY) were used to establish the location of water near the headgroup of a PC bilayer. 1H NMR comparisons of DOPC with a lipid that can hydrogen bond (monomethyldioleoylphosphatidylethanolamine, MeDOPE) showed the following trends: 1) the interlamellar water resonance was shifted to lower frequency for DOPC but to higher frequency for MeDOPE, 2) the chemical shift variation with temperature for interlamellar water was less than that of bulk water for MeDOPE MLVs, 3) water exchange between the two lipids was rapid on the NMR time scale if they were mixed in the same bilayer, 4) water exchange was slow if they were present in separate MLVs, and 5) exchange between bulk and interlamellar water was found by two-dimensional exchange experiments to be slow, and the exchange rate should be less than 157 Hz. These results illustrate the utility of ultra-high-resolution 1H MAS NMR for determining the nature and extent of lipid hydration as well as the arrangement of nuclei at the membrane/water interface.

Biophysical Phenomena↗
PubMed1999

Inhibiting gap junctional intercellular communication alters expression of differentiation markers in osteoblastic cells.

Gap junctional intercellular communication (GJIC) may contribute to cellular differentiation. To examine this possibility in bone cells we examined markers of cellular differentiation, including alkaline phosphatase, osteocalcin, and osteopontin, in ROS17/2.8 cells (ROS), a rat osteoblastic cell line expressing phenotypic characteristics of fully differentiated osteoblasts. We utilized ROS rendered communication deficient either by stable transfection with antisense cDNA to connexin 43 (Cx43), the predominant gap junction protein in bone (RCx16 cells), or by overexpression of Cx45, a gap junction protein not normally expressed in ROS (ROS/Cx45 cells). Both RCx16 and ROS/Cx45 cells displayed reduced dye coupling and Cx43 protein expression relative to ROS, control transfectants, and ROS/Cx45tr, ROS cells expressing carboxylterminal truncated Cx45. Steady-state mRNA levels for osteocalcin as well as alkaline phosphatase activity, two markers of osteoblastic differentiation, were also reduced in poorly coupled RCx16 and ROS/Cx45 cells. On the other hand, steady-state mRNA levels for osteopontin increased slightly in RCx16 and ROS/Cx45 cells. These results suggest that GJIC at least partly contributes to the regulation of expression of markers of osteoblastic differentiation.

Alkaline Phosphatase↗
PubMed1999

Antibody against murine PECAM-1 inhibits tumor angiogenesis in mice.

Platelet endothelial cell adhesion molecule (PECAM-1/CD31), a member of the immunoglobulin superfamily expressed at high levels on endothelial cells, has been recently implicated in angiogenesis. Although antagonism of PECAM-1 inhibited neovascularization in two different animal models of growth factor/chemokine-induced angiogenesis, its participation in tumor angiogenesis has not been established. We therefore investigated its involvement in models of tumor angiogenesis in mice. An antibody against murine PECAM-1 that was shown to block in vitro murine endothelial tube formation inhibited the subcutaneous growth and tumor vascularity of three tumors in mice: A549 human non-small cell lung cancer in SCID mice, B16 murine melanoma in C57BL/6 mice and AB12 murine mesothelioma in Balb/c mice. These studies suggest a possible role for PECAM-1 in the complex process of tumor angiogenesis and provide additional evidence of the importance of endothelial cell adhesion molecules to the formation of new vessels.

Journal Article↗
PubMed1999

A cellular assay distinguishes normal and mutant TIGR/myocilin protein.

Glaucoma is a blinding eye disease that affects approximately 70 000 000 people world-wide. Mutations in the gene TIGR / MYOC have been shown to cause the most common form of the disease, primary open angle glaucoma, in selected families. Amino acid sequence variants of the gene have been found in 2-4% of sporadic primary open angle glaucoma cases. Most variants are rare and it is often difficult to definitively distinguish between a deleterious mutation and a benign variant solely on the basis of relative frequencies in patient and control groups. The function of the TIGR/myocilin protein is unknown and an assay to functionally classify variants is lacking. We sought to develop a biochemical assay to distinguish different forms of TIGR/myocilin. We investigated the Triton X-100 detergent solubility characteristics of mutant and normal forms of the protein, expressed by transfection in cultured cells. We observed a clear difference in the behavior of the two types of TIGR/myocilin; all confirmed mutant proteins tested were substantially Triton insoluble, while normal protein and controls were completely soluble. We also tested seven ambiguous variant proteins and classified them as mutant or normal on the basis of their Triton solubility. The results in some cases validated, and in other cases contradicted, earlier classifications of these variants. To our knowledge, Triton solubility is the first example of a general difference in the properties of mutant and normal forms of TIGR/myocilin. The assay we have developed will be useful for discerning protein functional information from the location of mutations, will aid genetic counseling of individuals with TIGR/myocilin variants and may provide a clue to understanding a mechanism by which mutations in TIGR / MYOC cause glaucoma.

Amino Acid Substitution↗
PubMed1999

Entropic rigidity of randomly diluted two- and three-dimensional networks.

In recent work, we presented evidence that site-diluted triangular central-force networks, at finite temperatures, have a nonzero shear modulus for all concentrations of particles above the geometric percolation concentration p(c). This is in contrast to the zero-temperature case where the (energetic) shear modulus vanishes at a concentration of particles p(r)>p(c). In the present paper we report on analogous simulations of bond-diluted triangular lattices, site-diluted square lattices, and site-diluted simple-cubic lattices. We again find that these systems are rigid for all p>p(c) and that near p(c) the shear modulus mu approximately (p-p(c))(f), where the exponent f approximately 1.3 for two-dimensional lattices and f approximately 2 for the simple-cubic case. These results support the conjecture of de Gennes that the diluted central-force network is in the same universality class as the random resistor network. We present approximate renormalization group calculations that also lead to this conclusion.

Journal Article↗
PubMed1999

Droperidol lengthens cardiac repolarization due to block of the rapid component of the delayed rectifier potassium current.

INTRODUCTION: Torsades de pointes have been observed during treatment with droperidol, a butyrophenone neuroleptic agent. Our objectives were (1) to characterize the effects of droperidol on cardiac repolarization and (2) to evaluate effects of droperidol on a major time-dependent outward potassium current involved in cardiac repolarization (I(K)r). METHODS AND RESULTS: Isolated, buffer-perfused guinea pig hearts (n = 32) were stimulated at different pacing cycle lengths (150 to 250 msec) and exposed to droperidol in concentrations ranging from 10 to 300 nmol/L. Droperidol increased monophasic action potential duration measured at 90% repolarization (MAPD90) in a concentration-dependent manner by 9.8+/-2.3 msec (7.3%+/-0.7%) at 10 nmol/L but by 32.7+/-3.6 msec (25.7%+/-2.2%) at 300 nmol/L (250-msec cycle length). Increase in MAPD90 also was reverse frequency dependent. As noted previously, droperidol 300 nmol/L increased MAPD90 by 32.7+/-3.6 msec (25.7%+/-2.2%) at a pacing cycle length of 250 msec but by only 14.1+/-1.3 msec (13.6%+/-2.3%) at a pacing cycle length of 150 msec. Patch clamp experiments performed in isolated guinea pig ventricular myocytes demonstrated that droperidol decreases the time-dependent outward K+ current elicited by short depolarizations (250 msec; I(K)250) in a concentration-dependent manner. Estimated IC50 for I(K)250, which mostly underlies I(K)r, was 28 nmol/L. Finally, HERG K+ current elicited in HEK293 cells expressing high levels of HERG protein was decreased 50% by droperidol 32.2 nmol/L. CONCLUSION: Potent block of I(K)r by droperidol is likely to underlie QT prolongation observed in patients treated at therapeutic plasma concentrations (10 to 400 nmol/L) of the drug.

Action Potentials↗
PubMed1999

Block of HERG potassium channels by the antihistamine astemizole and its metabolites desmethylastemizole and norastemizole.

INTRODUCTION: The selective H1-receptor antagonist astemizole (Hismanal) causes acquired long QT syndrome. Astemizole blocks the rapidly activating delayed rectifier K+ current I(Kr) and the human ether-a go-go-related gene (HERG) K+ channels that underlie it. Astemizole also is rapidly metabolized. The principal metabolite is desmethylastemizole, which retains H1-receptor antagonist properties, has a long elimination time of 9 to 13 days, and its steady-state serum concentration exceeds that of astemizole by more than 30-fold. A second metabolite is norastemizole, which appears in serum in low concentrations following astemizole ingestion and has undergone development as a new antihistamine drug. Our objective in the present work was to study the effects of desmethylastemizole, norastemizole, and astemizole on HERG K+ channels. METHODS AND RESULTS: HERG channels were expressed in a mammalian (HEK 293) cell line and studied using the patch clamp technique. Desmethylastemizole and astemizole blocked HERG current with similar concentration dependence (half-maximal block of 1.0 and 0.9 nM, respectively) and block was use dependent. Norastemizole also blocked HERG current; however, block was incomplete and required higher drug concentrations (half-maximal block of 27.7 nM). CONCLUSIONS: Desmethylastemizole and astemizole cause equipotent block of HERG channels, and these are among the most potent HERG channel antagonists yet studied. Because desmethylastemizole becomes the dominant compound in serum, these findings support the postulate that it becomes the principal cause of long QT syndrome observed in patients following astemizole ingestion. Norastemizole block of HERG channels is weaker; thus, the risk of producing ventricular arrhythmias may be lower. These findings underscore the potential roles of some H1-receptor antagonist metabolites as K+ channel antagonists.

Astemizole↗
PubMed1999

Analysis of monoclonal antibodies to prostate-specific antigen: reactivity with native and recombinant prostate-specific antigen.

Epitope mapping analysis was performed on 53 antibodies submitted to the ISOBM TD-3 PSA Workshop. Western blotting and N-terminal amino acid sequencing, using both native and recombinant human prostate-specific antigen (rPSA), identified four different epitope groups for native PSA. Under reducing conditions native PSA was not recognized by 18/53 antibodies suggesting they reacted with conformation-dependent epitopes. Nine other antibodies reacted with a rPSA polypeptide doublet of 34-35 kD corresponding to different rPSA glycoforms. From sequence mapping studies 22/53 antibodies bound epitopes within amino acid residues 25-85, 3/53 antibodies bound to epitopes within residues 86-220, while 10/53 antibodies bound epitopes within residues 221-261. These results indicate that there are multiple immunogenic epitopes localized on the PSA molecule.

Antibodies, Monoclonal↗
PubMed1999

Evaluation of the baculovirus-expressed S glycoprotein of transmissible gastroenteritis virus (TGEV) as antigen in a competition ELISA to differentiate porcine respiratory coronavirus from TGEV antibodies in pigs.

The spike (S) glycoprotein of the Miller strain of transmissible gastroenteritis virus (TGEV) was recently cloned and expressed in baculovirus. The recombinant S protein was used as the coating antigen in a competition (blocking) enzyme-linked immunosorbent assay (ELISA) in combination with monoclonal antibodies to the S protein epitope A (conserved on TGEV and porcine respiratory coronavirus [PRCV]) or epitope D (present on TGEV only) to differentiate PRCV- from TGEV-induced antibodies. One set (set A) of 125 serum samples were collected at different times after inoculation of caesarean-derived, colostrum-deprived (n = 52) and conventional young pigs (n = 73) with 1 of the 2 porcine coronaviruses or uninoculated negative controls (TGEV/PRCV/negative = 75/30/20). A second set (set B) of 63 serum samples originated from adult sows inoculated with PRCV and the recombinant TGEV S protein or with mock-protein control and then exposed to virulent TGEV after challenge of their litters. Sera from set A were used to assess the accuracy indicators (sensitivity, specificity, accuracy) of the fixed-cell blocking ELISA, which uses swine testicular cells infected with the M6 strain of TGEV as the antigen source (ELISA 1) and the newly developed ELISA based on the recombinant S protein as antigen (ELISA 2). The sera from set B (adults) were tested for comparison. The plaque reduction virus neutralization test was used as a confirmatory test for the presence of antibodies to TGEV/PRCV in the test sera. The accuracy indicators for both ELISAs suggest that differential diagnosis can be of practical use at least 3 weeks after inoculation by testing the dual (acute/convalescent) samples from each individual in conjunction with another confirmatory (virus neutralization) antibody assay to provide valid and complete differentiation information. Moreover, whereas ELISA 1 had 10-20% false positive results to epitope D for PRCV-infected pigs (set A samples), no false-positive results to epitope D occurred using ELISA 2, indicating its greater specificity. The progression of seroresponses to the TGEV S protein epitopes A or D, as measured by the 2 ELISAs, was similar for both sets (A and B) of samples. Differentiation between TGEV and PRCV antibodies (based on seroresponses to epitope D) was consistently measured after the third week of inoculation.

Animals↗
PubMed1999

Ethnicity and migration as determinants of human prostate size.

The roles of ethnicity and migration in determining the size of human prostate zones during midlife were explored. Prostate size was measured by planimetric ultrasound in 163 men residing in Sydney who were either Australian non-Chinese (AR; n = 116) or Chinese migrants (ACM; n = 47) and had lived in Australia for a median of 7.3 yr (range, 0.2-25 yr). These were compared with Chinese men residing in China (CR; n = 210). Central and total prostate volumes were estimated by a single observer using the same equipment at both sites. After adjustment for age, central and total prostate volumes were significantly smaller, and plasma prostate-specific antigen and 5alpha-dihydrotestosterone (DHT) concentrations and International Prostate Syndrome Scores were significantly lower, in CR compared with either ACM or AR, whereas the scores of the latter two groups were similar. Almost all of the population difference in total prostate volumes could be accounted for by differences in central prostate volumes. The strongest correlates of age-adjusted prostate volume were prostate-specific antigen and DHT, the latter presumably reflecting the quantitative importance of prostatic stromal type II 5alpha-reductase activity to circulating DHT concentrations. Sex hormone-binding globulin concentrations were significantly higher in CR and significantly lower in ACM compared with those in AR, but the significance of these observations is unclear. These findings highlight the importance of the central zone of the prostate as well as provide evidence for an environmental factor influencing prostate growth. This factor operates over a relatively short time period compared with the evolution of prostate disease. Hence, this study provides evidence that ethnicity and geographical factors, such as migration, can influence the growth of the normal human prostate during midlife and may facilitate future studies of the origins and pathogenesis of human prostate disease.

Adult↗
PubMed1999

[Humoral and cell mediated immunity induced by HBV-S gene recombinant retroviral vector].

OBJECTIVE: To investigate the effectiveness of recombined retrovirus vector in gene therapy. METHODS: The retroviral vector PLXSN-S was constructed and transferred into PA317 by means of electroporation, then HepG2, P815, and EL4 cells were infected with the pseudovirus produced from PA317. In the meantime the gene immunization of PLXSN-S was also studied. RESULTS: HBsAg was expressed variously in the eukaryotic cells mentioned above and successfully evoked antibody response and CTL response to HBsAg after gene immunization. CONCLUSION: Intramuscular DNA immunization represents an efficient technique for priming CTL and antibody response to HBsAg. PLXSN may be used as an effective vector to carry genes of interest to target cells and immunization with it's DNA vaccine might be clinically useful for gene therapy.

Genetic Therapy↗
PubMed1999

Prostate-specific antigen and other serum markers: current concepts from the World Health Organization Second International Consultation on Prostate Cancer.

Serum prostate-specific antigen is credited with dramatic advances in the early detection, screening, and management of men with prostatic carcinoma. There has been more than a twofold increase in the number of men diagnosed during the last decade, and prostate cancer has emerged as the most common non-skin cancer and the second leading cause of cancer death in men. This report summarizes the history and current status of prostate-specific antigen and other serum markers, incorporating consensus opinions from the Second International Consultation on Prostate Cancer held in Paris in June 1999.

Age Factors↗
PubMed1999

[A method for preparation of carbon fiber electrode].

Carbon fiber electrode (CFE) can be used in detection of exocytosis of single neuron or endocrine cell. A simplified method for preparation of CFE, as described in the present paper, greatly ensures the coordination and success of the preparation. Such CFEs have a low noise level. Exocytosis of rat adrenal chromaffin cells was investigated in the clarification of the effect of MPP+ on transmitter release. It is found that exocytosis was not stimulated by MPP+ and the high K+ induced secretion was not changed by MPP+. These observations suggest that the previously reported elevation of dopamine content in the surrounding histosolution of DA neuron is probably resulted from blockage of the re-uptake of DA by MPP+.

1-Methyl-4-phenylpyridinium↗
PubMed1999

[Role of M-type receptor in internal calcium release and quantal secretion in rat adrenal chromaffin cells].

In rat single adrenal chromaffin cells, the effects of methacholine (MCh) on [Ca2+]i and catecholamine secretion were studied with fura-2 fluorescence and carbon fiber electrodes. In the presence of 2 mmol/L Ca2+ in the bath, locally applying 1 mmol/L MCh, either containing or not containing Ca2+, evoked both [Ca2+]i and secretion signals. In the absence of Ca2+ in the bath, MCh could still evoke [Ca2+]i and secretion. These results suggest that MCh causes release of Ca2+ from Ca2+ stores, which is sufficient to yield the evoked secretion. The Ca2+ store can be depleted by single MCh puff in the absence of Ca2+ in the bath.

Adrenal Medulla↗
PubMed1999

[Effects of acute hypoxia and hypoxic acclimatization on cardiac functions of rats].

OBJECTIVE: To study the effects of acute hypoxia and intermittent hypoxic acclimatization on cardiac systolic and diastolic functions in rats. METHOD: Cardiac functions were investigated after intermittent hypoxic acclimatizated (3000 m and 5000 m, 2 wk respectively, 4 h/d) and normoxic rats were exposed to hypoxia (8000 m) for 4 h. RESULT: The systolic functional parameters such as LVSP, +dp/dtmax, Vpm, Vmax and the diastolic functional parameter -dp/dtmax of acute hypoxic rats were reduced significantly as compared with normoxic control rats. After hypoxic acclimatization, the left ventricular functions of rats were increased significantly as compared with those of acute hypoxic rats. But they were still lower than those of normoxic control rats. CONCLUSION: Acute hypoxia can affect cardiac functions and hypoxic acclimatization can alleviate the hypoxic effects on cardiac functions.

Acclimatization↗
PubMed1999

A rapid one-step method of EIA for detection of circulating antigen of Schistosoma japonicum.

OBJECTIVE: To establish a highly sensitive serologic method for detecting the circulating antigen of Schistosoma japonicum for the diagnosis of this disease and the evaluation of drug therapy effect. METHODS: A set of complex support made of polyvinyl-chloride (PVC) film slide, adsorbed with specific antibody, was used to test serum samples collected from cases with schistosomiasis japonica, by adding specific enzyme conjugate and substrate tetra-methyl benzidine (TMB) with 3% H2O2 in 10:0.1, developed or prepared in our laboratory. Tests were carried out with the set on cases with malaria, paragonimiasis, clonorchiasis, visceral leishmaniasis and cysticercosis as well as normal individuals as control. Serum sample of 50 microliters was used in each test and reacted with reagents at room temperature for 30 minutes. The color of positive reaction was blue while negative reaction was colorless. RESULTS: Positive rate among cases with schistosomiasis japonica was 100% (45/45) in acute stage, 94.8% (530/559) in early chronic stage and 52.4% (66/126) in late stage. False positive reaction was found neither among all normal individuals (0/513), nor among cases of 155 with malaria, 120 with clonorchiasis, 24 with visceral leishmaniasis and 110 with cysticercosis, except one among 29 cases with paragonimiasis (1/29). CONCLUSIONS: The rapid one-step enzyme immunoassay (EIA) to detect circulating schistosome antigen (CSA) has been well established in our laboratory with high sensitivity and good specificity as well as reproducibility. The reaction result can be read easily even in field conditions without power supply. Moreover, the assay is time-saving, simple to handle and suitable for the diagnosis of schistosomiasis japonica and evaluation of drug therapeutic effect in practice in the control program of the disease.

Animals↗
PubMed1999

Diagnostic role of antibodies to glutamic acid decarboxylase in latent autoimmune diabetes mellitus in adults.

OBJECTIVE: To investigate the diagnostic role of antibodies to glutamic acid decarboxylase (GAD65-Ab) in latent autoimmune diabetes of adults (LADA) and the frequency of GAD-Ab in Chinese patients initially diagnosed as non-insulin-dependent diabetes mellitus (NIDDM). METHODS: Forty-five control subjects and 195 consecutive inpatients initially classified as NIDDM with > or = 35 years of age at onset and nonketotic history for > 6 months after diagnosis, were recruited. In vitro transcripted and translated recombinant human 35S-GAD65 was used in radioligand assay of GAD-Ab. RESULTS: The overall prevalence of GAD65-Ab was 14.8% (29/195) in NIDDM patients and 2.2% (1/45) in control subjects, respectively. Of the 29 GAD65-Ab positive patients, 17 (58.6%) were insulin-deficient while 12 (41.4%) were non-insulin-deficient. The prevalence of GAD65-Ab in NIDDM group with age of < 40 years at diabetes onset, ketotic history, body mass index (BMI) < 21 kg/m2, were significantly higher than that of corresponding control diabetic subgroups (2.5, 4.1 and 3.2 times, respectively). The sex, duration, symptoms of polyphagia, polydipsia, polyuria and weight loss at onset of the disease were not related to the prevalence of GAD65-Ab positivity. CONCLUSIONS: In China, patients initially diagnosed as NIDDM may in many cases suffer from LADA. Testing by GAD65-Ab may be of assistance to identifying LADA at the earliest stage of disease.

Adult↗