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Biomedical subjects

C Wang

Publications and source records attributed to C Wang.

At least 901 records · Page 50Linked to original sources
PubMed1995

Microsatellite instability in prostate cancer.

Assessment of the genetic instability of a microsatellite has indicated a new mechanism in human carcinogenesis. Examination was made to determine whether microsatellite instability is associated with the onset of prostate cancer. Twenty-nine DNA samples from 24 primary prostate cancer, two metastatic lymph-node and three benign prostatic hypertrophy patients were used. Differences in unrelated microsatellites for tumor and normal DNA were detected in nine of 24 (37.5%) cases. Seven of 11 (63.6%) with poorly differentiated adenocarcinomas and seven of 15 (46.7%) stage D metastatic patients showed somatic instability in a number of microsatellites. Statistically significant differences in well to moderately differentiated tumors and poorly differentiated cancer (P = 0.015, Chi-square test), were detected but not for stages A-C and D (P = 0.2311). Genetic alterations would thus appear to be rare in low grade and/or early prostate cancers but more common in high grade and/or advanced prostate cancers.

DNA Replication↗
PubMed1995

Pestivirus translation initiation occurs by internal ribosome entry.

The role of the 385 nucleotide 5' noncoding region (NCR) in the translation of the pestivirus genome was investigated. In vitro translation of an RNA transcript containing the 5' NCR of the bovine viral diarrhea virus (BVDV) genome followed by the coding sequence of the first gene product (p20) of the BVDV large open reading frame resulted in the synthesis of a 20-kDa polypeptide. Results from hybrid-arrest translation studies identified a region involving a predicted RNA stem-loop structure spanning nucleotides 154-261 within the 5' NCR that was important for p20 synthesis. An additional inhibitory oligonucleotide was complementary to the sequence at the base of this stem-loop and encompassed the initiating AUG at nucleotide 386. Antisense oligonucleotides both upstream and downstream of those that were inhibitory had no effect on p20 translation. RNA from a dicistronic expression vector in which the BVDV 5' NCR was inserted between two reporter genes, CAT and LUC, showed strong expression of the second (LUC) cistron upon in vitro translation. This expression was dramatically reduced in an analogous construct in which nucleotides 173-236 of the 5' NCR were deleted. Similar results were obtained when RNA from these same vectors was evaluated for expression after transfection into BHK cells. These results suggest that the BVDV 5' NCR contains an internal ribosome entry site for translation initiation. This translational mechanism is similar to that shown for hepatitis C virus, further demonstrating the close relationship between viruses of these two genera within the family Flaviviridae.

Animals↗
PubMed1995

[User guide to change endotracheal tubes].

A new way to manage artificial airway was introduced and estimated in this research. Six patients, who needed replacements of endotracheal tubes by varies reasons, were studied by using a guide wire through the existing endotracheal tube then removing the tube, and a new one was threaded over the wire into the trachea. During the procedure, the patient's HR,SaO2 and other clinical symptoms were monitored. It was compared with the control group of ten patients in which the old changing method was used. The result showed that average replacing time of study group, which was 30 sec, was much shorter than that of the control group, which was 20 min. there were no significant changes of HR and SaO2, no complications happened, and all the tubes were changed successfully with one time in study group. For the control group, the HR increased about 27 beats/min, SaO2 decreased about 10%, some patients were restlessness, had nose bleeding, or intubated into the esophagus and one patient had apnea. The success rate was only 67%. It is recommended that the new method is easier, less dangerous, less painful, and more successful.

Heart Rate↗
PubMed1995

Retrograde but not anterograde bead movement in intact axons requires dynein.

Dynein and kinesin have been implicated as the molecular motors that are responsible for the fast transport of axonal membranous organelles and vesicles. Experiments performed in vitro with partially reconstituted preparations have led to the hypothesis that kinesin moves organelles in the anterograde direction and dynein moves them in the retrograde direction. However, the molecular basis of transport directionality remains unclear. In the experiments described here, carboxylated fluorescent beads were injected into living Mauthner axons of lamprey and the beads were observed to move in both the anterograde and retrograde directions. The bead movement in both directions required intact microtubules, occurred at velocities approaching organelle fast transport in vivo, and was inhibited by vanadate at concentrations that inhibit organelle fast transport. When living axons were injected with micromolar concentrations of vanadate and irradiated at 365 nm prior to bead injections, a treatment that results in the V1 photolysis of dynein, the retrograde movement of the beads was specifically abolished. Neither the ultraviolet irradiation alone nor the vanadate alone produced the retrograde-specific inhibition. These results support the hypothesis that dynein is required for retrograde, but not anterograde, transport in vivo.

Animals↗
PubMed1995

Software trapping: a strategy for finding genes in large genomic regions.

We present an approach to the gene identification phase of positional cloning that combines sparse sampling of DNA sequences from large genomic regions with computational analysis. We call the method "software trapping." The goal is to find coding exons while avoiding massive DNA sequence determination and contig assembly. Instead, rapid sequence sampling is combined with exon screening software such as a newly developed package called XPOUND to identify coding sequences. We have tested the approach using a set of model genomic sequences with known intron/exon structures as well as with bona fide P1 genomic clones. The results suggest that the strategy is a useful complement to other methods for finding genes in poorly characterized regions of genomes.

Bacteriophage P1↗
PubMed1995

The effects of diquat and ciprofibrate on mRNA expression and catalytic activities of hepatic xenobiotic metabolizing and antioxidant enzymes in rat liver.

Although the mechanisms responsible for chemically induced oxidative stress are under intense investigation, little is known about the effects of prooxidant chemicals on the expression of drug-metabolizing enzymes. We examined the effects of diquat (0.1 mmol/kg, ip) and ciprofibrate (0.025% w/w, diet), chemicals which induce oxidative stress via different biochemical mechanisms, on the steady-state messenger RNA (mRNA) levels of six cytochrome P450 enzymes, seven glutathione S-transferase (GST) isoenzymes, UDP-glucuronosyl transferase 1-06 (UGT1*06), gamma-glutamylcysteine synthetase (gamma GCS), NADP(H):quinone oxidoreductase (quinone reductase), Cu/Zn superoxide dismutase (SOD), catalase, and 18S ribosomal RNA in the livers of male Sprague-Dawley rats. Effects of chemical treatments on mRNA levels were compared to changes in catalytic activities for selected enzymes. Ciprofibrate treatment selectively decreased CYP1A2 mRNA expression, whereas both chemicals suppressed CYP3A2 mRNA expression. CYP4A1 mRNA expression and lauric acid hydroxylase activities were induced by ciprofibrate treatment, whereas diquat treatment moderately increased CYP4A1 mRNA levels without affecting lauric acid hydroxylase activities. The steady-state mRNA levels encoding constitutively expressed GST isozymes (Ya1, Ya2, Yb1, Yb2, and Yc1) were decreased by diquat exposure, and the mRNA encoding four of the five constitutively expressed GSTs (Ya1, Ya2, Yb1, and Yc1) were also decreased by ciprofibrate treatment. Nonconstitutively expressed or low constitutively expressed genes (CYP1A1, CYP2B1, CYP2B2, GST Yc2, GST Yf, and UGT1*06) were not induced by exposure to the prooxidants. Changes in isozyme-specific catalytic activities were more consistent with the observed changes in mRNA expression for the GSTs than for the P450s. Both treatments had inhibitory effects on hepatic GSH biosynthesis by decreasing gamma GCS large-subunit mRNA expression, gamma GCS catalytic activities, and hepatic GSH concentrations. Cu/Zn SOD and quinone reductase mRNA levels were increased after ciprofibrate exposure, whereas Cu/Zn SOD mRNA expression was decreased in the diquat-treated animals. The results of this study indicate that diquat and ciprofibrate can decrease the expression profile of a number of phase I, phase II, and antioxidant enzymes and inhibit GSH biosynthesis. These effects may involve the pretranslational loss of hepatic mRNAs, possibly due to accelerated production of reactive oxygen species.

Animals↗
PubMed1995

Induction of phase I and phase II drug-metabolizing enzyme mRNA, protein, and activity by BHA, ethoxyquin, and oltipraz.

Various natural and synthetic compounds are known to protect against cancer by elevating phase II detoxification enzymes. Generally classified as monofunctional, these inducers are believed to trigger cellular signal(s) that activate gene transcription through an antioxidant or electrophile response element (ARE/EpRE) in responsive genes. In contrast, the phase I enzymes of drug metabolism (cytochrome P450s) are not believed to be induced by monofunctional inducers and P450 genes have not been found to contain functional ARE/EpREs. In this study, rats were treated with the monofunctional inducers tert-butylated hydroxyanisole, ethoxyquin, and oltipraz to study the inducibility of individual glutathione S-transferase isozymes, NADP(H):quinone oxidoreductase, gamma-glutamylcysteine synthetase, UDP-glucuronosyl transferase, and cytochrome P450 enzymes. Hepatic mRNAs were analyzed on Northern blots using gene-specific oligonucleotide probes for GST Ya1, Ya2, Yc1, Yc2, Yb1, Yb2, and Yf, for UGT 1*06, and for P450 1A1, 1A2, 2B1, 2C11, 3A2, and 4A1. NADP(H):quinone oxidoreductase and gamma-glutamylcysteine synthetase mRNAs were detected using cDNA probes. All the phase II detoxification enzymes analyzed, except GST Yf, were induced by the three monofunctional inducers, suggesting that these genes may be regulated by a mechanism involving an ARE/EpRE element in their promoter region. Interestingly, it was found that ethoxyquin was a particularly good inducer for both members of the P450 2B family, 2B1 and 2B2, and both ethoxyquin and oltipraz were also capable of modestly inducing P450 1A2 and 3A2. Oltipraz was found to slightly induce P450 2B2, but not 2B1, at the dose and time analyzed. Induction of mRNA generally correlated well with induction of protein levels determined by Western blot and/or enzyme activity measurements for selected enzymes. The results of this study suggest that many phase II enzymes may contain ARE/EpRE elements in addition to those confirmed to be regulated by a mechanism involving ARE/EpRE elements. In addition, it was found that several P450 enzymes were induced by monofunctional inducers, suggesting a possibility that some phase I enzymes may also be regulated by a mechanism involving ARE/EpRE elements.

Animals↗
PubMed1995

The anti-progestin CDB 2914 has no antifertility effect in male rats.

This study examines the effect of an anti-progestin (CDB 2914) with antiprogestational potencies similar to RU 486 on spermatogenesis, sperm maturation, and fertility in male rats. Adult male rats of proven fertility were administered the anti-progestin (10 mg/kg/day) or vehicle (control group) for 14, 35, and 70 days to study the possible effect of this compound on epididymal sperm maturation, post-meiotic sperm development, spermatogenesis, and fertility, respectively. Fertility rates of the rats were determined by mating studies. The anti-progestin, CDB 2914, had no effect on testis or accessory organ weights, epididymal sperm content or motility, testicular sperm count, spermatogenesis, and fertility of male rats. This study suggests that anti-progestins, when administered even at higher doses than those used in humans, have no contraceptive effect in adult male rats.

Animals↗
PubMed1995

Plasma levels of beta-endorphin, leucine enkephalin and arginine vasopressin in patients with essential hypertension and the effects of clonidine.

In order to investigate the changes of endogenous opiate systems in hypertension and their possible role in the pathogenesis in hypertension, we measured plasma concentrations of beta-endorphin, leucine-enkephalin, neurotension, arginine vasopressin, plasma renin activity and angiotensin II by radioimmunoassay in 60 normal persons and 120 patients with essential hypertension. The results showed that the patient group had lower levels of beta-endorphin and leucine enkephalin (P < 0.001), higher levels of arginine vasopressin, plasma renin activity and angiotensin II (P < 0.01, P < 0.05 and P < 0.05, respectively), and normal level of neurotensin, as compared with those in normal group. Plasma levels of leucine-enkephalin was correlated negatively to the mean artery pressure (r = -0.196, P < 0.05). Plasma level of arginine vasopressin was correlated to the duration of the hypertension (r = 0.216, P < 0.05). After 150 min and 14 days of treatment with clonidine, plasma levels of beta-endorphin, leucine-enkephalin increased significantly (< 0.01) and correlated negatively with the decrease of the mean artery pressure (r = -0.340 and r = -0.436 at 150 min, r = -0.369 and r = -0.441 on the 14th day, respectively, P < 0.01). Plasma renin activity and angiotensin II decreased significantly (P < 0.05 and P < 0.01). Arginine vasopressin and neurotensin did not change significantly. After intravenous administration of opiate antagonist-naloxone, the blood pressure and heart rate increased significantly (P < 0.01). The results suggested that the changes of endogenous opioids may be involved in the pathogenesis of hypertension and in the antihypertensive action of clonidine.

Angiotensin II↗
PubMed1995

Genotoxicity in the rodent urinary bladder.

Elucidation of the mechanisms by which a chemical may induce urinary bladder tumours in rodents can be expected to provide insight into the relative risk from that agent. The methodologies for exploring whether tumour induction may be a response to direct genotoxic effect of the compound have been successfully applied to the bladders of both mice and rats. Thus, with experimental approaches that utilize adduct detection through the use of immunochemical and postlabelling techniques, unscheduled DNA synthesis and mutagenicity as studied with transgenic animals it is possible to obtain fundamental information on the genotoxic potential of carcinogens in the target bladder. Application of these experimental approaches to carcinogens for which the mechanisms of action are not known should permit assessment of the likelihood that genotoxic or non-genotoxic mechanisms are involved in the tumour induction process. Moreover, such studies may provide knowledge of the molecular pathways that are involved in the action of genotoxic agents, thus enabling judgements to be made as to whether humans are subject to tumour induction by the chemical.

Animals↗
PubMed1995

Activation of the M2 ion channel of influenza virus: a role for the transmembrane domain histidine residue.

To test the hypothesis that transmembrane domain histidine residue 37 of the M2 ion channel of influenza A virus mediates the low pH-induced activation of the channel, the residue was changed to glycine, glutamate, arginine, or lysine. The wild-type and altered M2 proteins were expressed in oocytes of Xenopus laevis and membrane currents were recorded. The mass of protein expressed in individual oocytes was measured using quantitative immunoblotting and correlated with membrane currents. Oocytes expressing the M2-H37G protein had a voltage-independent conductance with current-voltage relationship similar to that of the wild-type M2 channel. The conductance of the M2-H37G protein was reversibly inhibited by the M2 ion channel blocker amantadine and was only very slightly modulated by changes in pHout over the range pH 5.4 to pH 8.2. Oocytes expressing the M2-H37E protein also had a voltage-independent conductance with a current-voltage relationship similar to that of the wild-type M2 channel. The conductance of the M2-H37E protein was reversibly inhibited by amantadine and was also only very slightly modulated by changes in pHout over the range pH 5.4 to pH 8.2. These slight alterations in conductance of the mutant ion channels on changes in pHout are in striking contrast to the 50-fold change in conductance seen for the wild-type M2 channel over the range pH 4.5 to pH 8.2. The specific activity of the M2-H37G protein was 1.36 +/- 0.37 microA/ng and the specific activity of the M2-H37E protein was 30 +/- 3 microA/ng at pH 6.2. These values of specific activity greatly exceed that of the wild-type protein at the same pH (0.16 + 0.01 micro A/ng). Oocytes expressing the M2-H37K and M2-H37R mutant proteins could not be studied because the oocytes did not survive more than a few hours in culture. Oocytes expressing the M2-H37E mutant protein also had a voltage-activated Cl- conductance that was observed only for oocytes that expressed a mass of protein exceeding a large threshold value. These results are consistent with protonation of histidine residue 37 as an essential step in the activation of the wild-type M2 ion channel.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1995

Calcium-mediated disintegrative globulization of isolated ocular lens fibers mimics cataractogenesis.

Single viable fiber cells have been isolated from the cortex of rat ocular lens by proteolytic digestion of the intact lens in calcium-free media. In isomolar sucrose, the isolated cells maintain their fiber-shaped morphology and exclude trypan blue. The surface morphology of the isolated fiber cells appears to be largely unaffected by the isolation procedure. The concentrations of adenine nucleotides, GSH, GSSG and the rate of glycolysis in the isolated fiber cells were comparable to those in the cortex. Upon perfusion of the tissue chamber with Ringer's solution, the fiber cells undergo a series of transformations, beginning with cell swelling, periodic blebbing along the longitudinal cellular axis, and eventual disintegration of the fiber into a number of resealed globules or round cells which resemble light-scattering areas in human cortical and supranuclear cataract. This disintegrative globulization of the fiber cells appears to be mediated by calcium influx, as it was prevented or delayed by a reduction in extracellular calcium concentration, verapamil or lanthanum. Since disturbances in calcium homeostasis are associated with various forms of cataract, such Ca(2+)-mediated disintegrative globulization of the fiber cells may be responsible for the formation of light scattering centers during cataractogenesis.

Adenosine Monophosphate↗
PubMed1995

Evaluation of the CellTrak computer-assisted sperm analysis system in comparison to the Cellsoft system to measure human sperm hyperactivation.

OBJECTIVE: To measure and compare sperm hyperactivation (HA) and associated motility parameters using the CellTrak (Motion Analysis Corporation, Santa Rosa, CA) and Cellsoft (Cryo Resources, New York, NY) Computer-Assisted Sperm Analysis (CASA) Systems. The accuracy of the CellTrak system also was assessed by repeated measurements of the same sample. SETTING: A university-affiliated tertiary care center. PATIENTS: Normal healthy volunteers. MAIN OUTCOME MEASURES: We assessed sperm motion parameters and HA. RESULTS: The measurements of percent spermatozoa with star and/or transitional pattern of HA showed high within-sample variations, especially in samples showing low levels of percent spermatozoa with HA. This was due to the comparatively low numbers of hyperactivated spermatozoa that were present and counted in a sample. Excellent agreement between the two systems was observed for all parameters except for measurements of curvilinear velocity, percent spermatozoa with star-spin hyperactivity, and percent spermatozoa with transitional hyperactivity. The difference might be due to CellTrak's higher level of accuracy in determining velocity. CONCLUSIONS: The CellTrak system effectively measures human sperm HA provided adequate numbers of motile spermatozoa are analyzed. Although it suffers from the same limitations common to all CASA systems, it is more accurate than the Cellsoft system.

Computers↗
PubMed1995

Lipid peroxidation accompanies cyclosporine nephrotoxicity: effects of vitamin E.

Cyclosporine A (CsA) has been demonstrated to induce renal microsomal lipid peroxidation in vitro. To examine whether CsA induces lipid peroxidation in vivo, uninephrectomized rats were gavaged with vehicle, CsA 12.5 or 25 mg/kg/day for four weeks. CsA-induced reduction in GFR and RBF was associated with a dose-related increase in renal cortical malondialdehyde (MDA) and conjugated diene, as well as a similar increase in arterial MDA. The latter was apparent within two hours of a single intraperitoneal injection of 25 mg/kg CsA and preceded the acute fall in GFR. To address whether lipid peroxidation contributed to CsA nephrotoxicity, rats were gavaged with vehicles, CsA 25 mg/kg/day or CsA plus vitamin E 25 mg/kg/day for eight weeks. Vitamin E, a lipid radical scavenger, inhibited MDA raise and reduced CsA-induced renal damage. Conversely, CsA administration to vitamin E and selenium deficient rats was accompanied by a greater increase in arterial MDA and fall in GFR. These novel findings, that CsA nephrotoxicity is associated with lipid peroxidation and that a chain-breaking antioxidant ameliorates whereas its deficiency exacerbates, indicate a role for lipid peroxidation, presumably free radical-mediated, in CsA toxicity.

Animals↗