Biomedical subjects

R Y Wang

Publications and source records attributed to R Y Wang.

At least 55 records · Page 3Linked to original sources

PubMed1998

High-frequency DNA rearrangements in the chromosomes of clinically isolated Mycoplasma fermentans.

Mycoplasma fermentans is currently being examined as an agent potentially associated with human disease. Several strains of M. fermentans were isolated from patients with respiratory tract disease and AIDS. Two of these clinical strains, M64 and SK6, were triple-filter-cloned and designated as the parental clones in this study. Genomic DNA of randomly picked subclones in four and five subsequent generations passed from the parental M64 and SK6 clones were analyzed by using a radiolabeled M. fermentans-specific insertion sequence (IS)-like element as the probe. The hybridization patterns of DNA restriction fragments revealed high frequencies of chromosomal changes accompanied with excision or new insertion of the IS-like element in M. fermentans chromosome. The findings indicate M. fermentans has an effective mechanism(s) to produce a rapid gene rearrangement that may be mediated by one or more copies of the IS-like element.

Blotting, Southern↗

PubMed1998

Delayed hypoglycemia in a child after ingestion of a single glipizide tablet.

This is the first report to describe the delayed onset of hypoglycemia in a child after ingestion of one tablet of glipizide. A 2-year-old boy was observed to ingest 5 mg glipizide and 25 mg hydrochlorothiazide. Activated charcoal was administered within 35 minutes of ingestion. Hypoglycemia (serum glucose 49 mg/dL) developed 11 hours later. Emergency physicians must be aware of the potential for delayed hypoglycemia in children with single-tablet ingestions of glipizide. Prolonged monitoring of glucose levels is warranted.

Antihypertensive Agents↗

PubMed1998

M100907, a selective 5-HT2A receptor antagonist and a potential antipsychotic drug, facilitates N-methyl-D-aspartate-receptor mediated neurotransmission in the rat medial prefrontal cortical neurons in vitro.

The technique of intracellular recording was used to examine the effect of M100907 (formerly MDL 100907), a highly selective 5-HT2A receptor antagonist and a potential antipsychotic drug (APD), on N-methyl-D-aspartate (NMDA) and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor-mediated responses in pyramidal cells of the rat medial prefrontal cortex in in vitro brain slice preparations. Bath administration of M100907, but not its inactive stereoisomer M100009, produced a 350% to 550% increase of NMDA-induced responses in a concentration-dependent manner with an EC50 value of 14 nmol/L, reminiscent of the action of clozapine. M100907 did not alter AMPA responses. Moreover, M100907 significantly increased the amplitude and duration of excitatory postsynaptic potentials and currents evoked by electrical stimulation of the forceps minor. We have generated several lines of evidence indicating that M100907 enhances glutamate receptor-mediated neurotransmission in pyramidal cells of the medial prefrontal cortex by facilitating NMDA-induced release of excitatory amino acids. The robust potentiation of NMDA receptor-mediated neurotransmission may explain, at least partly, the potential antipsychotic action of this compound. Furthermore, if M100907 proves to be an effective APD and if our findings can be extended to other atypical APDs, which are known to possess a relatively high affinity to 5-HT2A receptors, they may account for the purported efficacy of atypical APDs in alleviating some negative symptoms such as cognitive and executive functions.

Animals↗

PubMed1998

M100907 and clozapine, but not haloperidol or raclopride, prevent phencyclidine-induced blockade of NMDA responses in pyramidal neurons of the rat medial prefrontal cortical slice.

In the present study, we demonstrate that, in a concentration-dependent manner, M100907 (formerly MDL 100907, a highly selective 5-HT2A receptor antagonist and a purported atypical antipsychotic drug [APD]), but not its much less active stereoisomer M100009, completely prevents or markedly reverses the phencyclidine (PCP)-induced blockade of N-methyl-D-aspartate (NMDA) responses in pyramidal neurons of the medial prefrontal cortex (mPFC). Furthermore, the atypical APD clozapine, but not the typical APD haloperidol or raclopride (a selective dopamine D2,3 receptor antagonist), mimicked the action of M100907, preventing the PCP-induced effect. These results suggest that M100907 might be an antidote for treating the PCP-induced psychotomimetic state that closely resembles schizophrenia; they could also account for the antipsychotic potential of M100907. Furthermore, our results suggest that the prototype (clozapine) and a candidate (M100907) atypical APDs might be effective in ameliorating schizophrenic symptoms including cognitive and neuropsychological deficits, which are induced in humans who abuse PCP. We hypothesize that the ability of M100907 and clozapine to prevent or reverse the PCP-induced blockade of the NMDA receptor channel is attributed to their 5-HT2A receptors antagonizing property. Therefore, with further systematic studies, the ability of compounds to prevent or reverse PCP's blockade of NMDA responses may prove to be an effective electrophysiological model for screening potential atypical APDs and predicting their therapeutic efficacy in cognitive deficits.

Animals↗

PubMed1998

Role of the helper component in vector-specific transmission of potyviruses.

Four aphid species were tested for their ability to transmit tobacco etch (TEV) and turnip mosaic (TuMV) potyviruses. Myzus persicae and Aphis gossypii transmitted both viruses efficiently from infected plants, whereas Lipaphis erysimi transmitted only TuMV and Myzus ascalonicus was a poor or non-transmitter of either virus. Similar electrically monitored probing patterns were produced by M. persicae, L. erysimi and M. ascalonicus, ruling out behavioural differences as the cause of differential transmission. Transmission results similar to those from infected plants were obtained when these aphids acquired homologous virus/helper component (HC) mixtures through membranes. With heterologous virus/HC mixtures, M. persicae remained a highly efficient vector and M. ascalonicus a non-vector, but L. erysimi became an efficient vector of TEV if acquired in the presence of TuMV HC and A. gossypii transmitted both viruses less efficiently when acquired with TuMV HC. Transmission was highly correlated with the retention of virus in the stylets, as determined by autoradiography of 125I-labelled virions. The results show that constituent(s) of or in the food canal of different aphid species differ in their ability to interact with specific HCs, leading to qualitative or quantitative differences in ability to retain and subsequently transmit specific potyviruses.

Animals↗

PubMed1998

Exaggerated precocious centromere separation in cells of a human breast cancer line treated with a green tea extract.

In a breast cancer cell line, MDA-MB-468, established in our laboratory, an average of 3% of the mitotic cells exhibited a phenomenon known as centromere splaying, which is a characteristic feature of cells of patients with Roberts syndrome. However, centromere splaying in cells of Roberts syndrome patients is limited to i) the centromere region and ii) chromosomes with large amounts of heterochromatin. When the breast cancer cells were treated with an extract of green tea GTE-TP91, up to 45% of the metaphases were observed to exhibit this behavior; and the precocious centromere separation was highly exaggerated, affecting all chromosomes in such metaphases. Apparently, as the sister centromeres continued to pull apart, they carried the chromatids with them, except for the telomere regions, giving a ring-like configuration. Eventually, the sister chromatids became completely separated. Whether this bizarre phenomenon was induced by the polyphenols contained in this green tea extract GTE-TP91 is not known, but this phenomenon, upon further investigation, may throw some light on chromosomal proteins, centromere behavior, telomere behavior and related questions.

Breast Neoplasms↗

PubMed1997

NMDA-induced response in pyramidal neurons of the rat medial prefrontal cortex slices consists of NMDA and non-NMDA components.

Using the techniques of intracellular recording, we examined and characterized the membrane response induced by N-methyl-D-aspartate (NMDA) and compared the excitatory postsynaptic potentials (EPSPs) elicited by NMDA and by electrical stimulation of the forceps minor in presumed pyramidal cells of the rat medial prefrontal cortex (mPFC) slice preparation. Bath application of NMDA produced EPSPs, membrane depolarization, and bursts of action potentials. These effects were completely blocked by the NMDA receptor antagonist D-2-amino-phosphonopentanoic acid (d-AP5). The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dion (CNQX) markedly decreased NMDA-induced responses and converted the I-V relationship curve of NMDA from a curvi-linear to the characteristic J-shape, thus indicating the existence of a non-NMDA component. Synaptic responses elicited by electrical stimulation of the forceps minor also consisted of NMDA and non-NMDA components. Both NMDA- and electrical stimulation-elicited EPSPs were markedly reduced or completely abolished by using Ca2+-free artificial cerebrospinal fluid (ACSF), ACSF containing either TTX, low Ca2+ plus Cd2+, or a membrane permeable Ca2+ chelator BAPTA-AM (when BAPTA was loaded in the recording electrode, it was without effect). Under these conditions, NMDA-induced depolarization was significantly reduced. Taken together, these results suggest that in addition to a direct action on pyramidal neurons, NMDA causes a release of excitatory amino acids (EAAs), which in turn activate non-NMDA receptors.

2-Amino-5-phosphonovalerate↗

PubMed1997

Pediatric gamma hydroxybutyrate intoxication.

Reported are 2 uncommon cases of childhood gamma hydroxybutyrate (GHB) toxicity and the surreptitious manner in which GHB was made. Two children unintentionally ingested a soft drink containing GHB and were found comatose. Both had been well 1 hour earlier. The parent had made GHB by combining gamma butyrolactone with caustic soda (sodium hydroxide). Symptoms were early in onset and resolved in 24 hours. The ECG changes in one case are unique to GHB toxicity and are unexplained. GHB-toxic children appear similar to adults who have this poisoning. Supportive management remains the mainstay of therapy. Health care providers should be aware of GHB's clandestine production and its increasing presence on the streets and in the home. This agent is not detected with common drug screens.

Child↗

PubMed1997

Mycoplasma genitalium infection and host antibody immune response in patients infected by HIV, patients attending STD clinics and in healthy blood donors.

Prevalence of Mycoplasma genitalium in humans is still not clear. We have developed a sensitive and specific serological assay for M. genitalium using lipid-associated membrane proteins (LAMPs) as antigens. Antibodies to LAMPs from M. genitalium showed little cross-reactivity to LAMPs from antigenically similar M. pneumoniae. For validity testing, urines from 104 patients were tested by PCR for M. genitalium. All 15 PCR+ patients had M. genitalium-LAMPs antibodies. Moreover, none of 64 antibody-negative patients were PCR+. Serological study of 1800 patients of various diseased groups and healthy blood donors showed M. genitalium was primarily a sexually transmitted microbe that infected patients with AIDS (44.0%), intravenous drugs users with or without HIV infection (42.5%), and also HIV- patients attending STD clinics (42.6%). Only 5.5% HIV- healthy blood donors and 1.3% HIV+ hemophiliacs tested positive. M. genitalium has been associated with acute non-gonococcal urethritis in male patients. However, many sexually active men and women appear to be chronically infected or colonized by the microbe without apparent clinical symptoms and may continue to transmit the organism through sexual contacts.

Antibodies, Bacterial↗

PubMed1997

Antidotal efficacy of glutamate and aspartate for colchicine toxicity.

Glutamic and aspartic acids were evaluated for their antidotal efficacy in colchicine toxicity. Female adult inbred mice were treated with ip doses of either 1000 mg glutamic acid (GA) or aspartic acid (AA)/kg bw by various treatment schedules relative to the administration of an ip LD5n of 7.8 mg colchicine/kg bw. Mice were observed for survival and changes in body weight. Pretreatment with AA increased survival by 42% (p = 0.01). Concurrent AA treatment improved survival non-significantly (p = 0.07). With post-exposure AA therapy, however, mortality was increased (p = 0.005). No significant beneficial effects of GA occurred. Early AA therapy improves survival in colchicine poisoned mice, but as delay in treatment is increased, AA efficacy is lost.

Animals↗

PubMed1997

Clozapine and haloperidol modulate N-methyl-D-aspartate- and non-N-methyl-D-aspartate receptor-mediated neurotransmission in rat prefrontal cortical neurons in vitro.

The effects of the antipsychotic drugs haloperidol and clozapine on N-methyl-D-aspartate (NMDA) and non-NMDA receptor-mediated neurotransmission were examined and compared in pyramidal cells of the medial prefrontal cortex in rat brain slices by using the techniques of intracellular recording and single-electrode voltage-clamp. The bath administration of either haloperidol or clozapine produced a marked facilitation (300-400%) of NMDA-evoked responses in a concentration-dependent manner. The EC50 values of haloperidol and clozapine were 38 and 14 nM, respectively. At concentrations of > or =100 nM, clozapine, but not haloperidol, produced bursts of excitatory postsynaptic potentials (EPSPs), which were blocked by glutamate receptor antagonists, suggesting that these EPSPs were the result of increasing release of excitatory amino acids. Haloperidol, but not clozapine, produced a concentration-dependent inhibition of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced current with an EC50 value of 37 nM. Haloperidol significantly decreased the amplitude of EPSPs evoked by the electrical stimulation of the forceps minor, whereas clozapine increased the amplitude of these EPSPs. The study of current-voltage relationship indicates that clozapine preferentially potentiates NMDA receptor-mediated transmission, whereas haloperidol depresses the non-NMDA receptor-mediated response, which probably obscures its potentiating effect on NMDA receptor-mediated EPSPs.

Action Potentials↗

PubMed1997

[The analysis of schizophrenic inpatients' escape behavior].

To study the escaping behavior of 1030 schizophrenic in-patients, "Brief Rating Scale for Dangerous Behavior of In-patient" was used to asses them within their first week hospitalization from May 1994 to March 1996. The result showed that 276 (26.8%) patients had escaping behavior. The patients with paranoid schizophrenia had higher rate of escaping behavior. There was no correlation being found between sex, age, duration of illness, and escaping behavior. The patients with the history of such behavior were more likely to escape from ward (41.9%). The suggestion for preventing such behavior were discussed.

Adolescent↗

PubMed1996

Translocations and deletions of 5q13.1 in myelodysplasia and acute myelogenous leukemia: evidence for a novel critical locus.

Acquired partial and complete deletions of chromosome 5 (5q-, -5) are common cytogenetic anomalies associated with myelodysplasia (MDS) and acute myeloid leukemia (AML). A critical region of consistent loss at 5q31.1 (in > 90% of cases) has led us and others to postulate the presence of a key negative regulator(s) of leukemogenesis. Although the interstitial deletion limits vary among patients, del(5) (q13q33) and del(5)(q13q35) constitute major subsets. Furthermore, it is not rare to encounter deletions, translocations, or paracentric inversions involving 5q11 to 5q13, which indicates inactivation or disruption of important gene(s) at that locus. In this report, we have localized a novel locus at 5q13.1 to a 2.0-Mb interval between the anonymous markers D5S672 and GATA-P1804. This locus resided within the region of loss in 12 of 27 patients with anomalies of chromosome 5; one of these cases had apparent retention of both alleles of all the telomeric loci. Fluorescence in situ hybridization (FISH) studies demonstrate that the AML cell line ML3 is disrupted at 5q13.1 by a translocation involving chromosome 3, with apparent retention of the entire chromosome 5 sequence. Our results suggest that this novel proximal locus encodes a critical gene that may be deleted or disrupted in a subset of MDS/AML patients with chromosome 5 anomalies.

Adult↗

PubMed1996

5-HT3-like receptors in the rat medial prefrontal cortex: further pharmacological characterization.

The aim of the study was to further characterize the pharmacological properties of 5-hydroxytryptamine (5-HT)3-like receptors in the rat medial prefrontal cortex (mPFC) using combinations of biochemical and electrophysiological approaches. Phenylbiguanide (PBG) and three chlorinated derivatives, ortho-chloro-PBG (oCPBG), meta-chloro-PBG (mCPBG) and para-chloro-PBG (pCPBG), dose-dependently stimulated phosphoionositide (PI) turnover in fronto-cingulate cortical slices. All three chloro-isomers of PBG were equipotent in stimulating PI turnover. SR 57227A ((4-amino)-(6-chloro-2-pyridyl) L-piperidine hydrochloride, a novel compound with high affinity and selectivity for peripheral and central 5-HT3 receptors) dose-dependently stimulated PI turnover in fronto-cingulate cortical slices. The rank order of potency of all the 5-HT3 receptor agonists tested in the PI assay as compared to 5-HT was: 5-HT > 2-Me-5-HT > SR57227A > PBG = mCPBG = oCPBG = mCPBG. 5-HT and 5-HT receptor agonists depressed the firing rate of both spontaneously active and glutamate-activated quiescent mPFC cells in a current (dose)-dependent fashion. The rank order of effectiveness of these compounds was: 5-HT > SR57227A = 2-Me-5-HT = mCPBG = oCPBG = pCPBG = PBG. Unlike its action on the 5-HT3 receptors in the periphery or cultured cell lines, D-tubocurarine chloride appears to be non-specific in blocking the depressant action of 2-Me-5-HT, gamma-aminobutyric acid and dopamine. Our results combined support the view that the pharmacological properties of 5-HT3-like receptors in the mPFC are not identical to those located in peripheral tissues and in cultured cell lines.

Animals↗

PubMed1996

Examination of the action of 3,4-methylenedioxymethamphetamine on rat A10 dopamine neurons.

Extracellular single cell recording was used to examine the effect of intravenous administration of (-), (+), and (+/-)-3,4-methylenedioxymethamphetamine (MDMA) on A10 dopamine (DA) neurons in chloral hydrate anesthetized male rats. Both (+/-)-MDMA and (+)-MDMA inhibited the firing rate of most (79%) A10 DA cells. By contrast, (-)-MDMA induced either no effect or a slight increase in the firing rate of these cells. Analysis of the effects of (+/-)-MDMA on the firing pattern of the DA cells revealed on overall decrease in the percentage of spikes in bursts but both increases and decreases were seen in the coefficient of variation of interspike intervals. To determine the contribution of 5-HT and DA to the (+/-)-MDMA-induced inhibition of A10 DA cells rats were pretreated either with the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA) or the DA synthesis inhibitor alpha-methyl-p-tyrosine (AMPT). Pretreatment of rats with PCPA did not reduce the ability of (+/-)-MDMA to inhibit the DA cells. However, in rats pretreated with AMPT, the (+/-)-MDMA-induced inhibition was blocked and some cells (44%) showed instead an increase in firing rate following administration of (+/-)-MDMA. The administration of l-3,4-dihydroxyphenylalanine (L-DOPA) to AMPT-treated rats rapidly restored the inhibition of cell firing by (+/-)-MDMA. In conclusion, the results reported here demonstrate that MDMA has an overall inhibitory effect on A10 DA cells. Despite MDMA's greater potency in releasing 5-HT compared to DA, the inhibitory effect of this drug on A10 DA cells appears to be mediated by the latter transmitter.

Animals↗

PubMed1996

Pharmacological actions of the atypical antipsychotic drug clozapine: a review.

Clozapine [8-chloro- 11-(4-methyl- 1-piperazinyl)-3H-dibenzo (b,e)(1,4) diazepine], or clozaril, is a member of the dibenazepine class of antipsychotic drugs. Initially, studies in animals using a number of neurochemical, biochemical, electrophysiological, and behavioral paradigms indicated that clozapine was markedly different from various typical antipsychotic drugs such as haloperidol and chlorpromazine. Subsequently, clinical studies have shown that clozapine is effective in ameliorating the core symptoms, as well as the negative symptoms, in schizophrenia. However, clozapine has a much lower propensity for inducing neurological side effects after acute or repeated administration compared to various typical neuroleptics. Furthermore, clozapine is therapeutically effective in treating about 30% of schizophrenic patients who are resistant to standard antipsychotic drugs. Based on the above information, clozapine has been designated an atypical antipsychotic drug. However, at this time, it is not entirely clear why clozapine is such a unique antipsychotic drug. To date, there has not been a comprehensive review regarding clozapine's pharmacological profile. Therefore, we will review clozapine's profile in the following areas: 1) affinity for neurotransmitter receptors in the brain; 2) electrophysiology (in vivo, single-cell recording and iontophoresis; in vitro studies); 3) in vivo microdialysis and voltammetry; 4) monoamine turnover or metabolism; 5) intermediate early gene expression; 6) positron emission tomography studies; and 7) molecular biological studies. We will also compare and contrast clozapine's acute and chronic effects, and discuss the merits of various hypotheses that have been put forward to explain clozapine's unique profile.

Animals↗

PubMed1996

Modulation of the A10 dopamine system: electrophysiological studies of the role of 5-HT3-like receptors.

The distribution of 5-HT3-like receptors is primarily in the mesocorticolimbic structures. We have previously demonstrated that the atypical antipsychotic drug clozapine and a structurally related compound RMI 81,582 differ from other typical antipsychotic drugs in that they are effective 5-HT3 receptor antagonists. Our experimental results suggest that 5-HT3-like receptors play a permissive role in regulating or gating the inhibitory action of dopamine in the mesocorticolimbic areas. We hypothesize that the ability of clozapine to antagonize both 5-HT3-like and dopamine receptors may account for its preferential interaction with the mesocorticolimbic dopamine system and the higher efficacy in treating the schizophrenic symptoms.

Animals↗

PubMed1996

Encephalopathy and cranial nerve palsies caused by intentional trichloroethylene inhalation.

This report describes an acute intentional trichloroethylene exposure that developed neurological and cardiovascular toxicity. The patient presented with palsies of the third, fifth, and sixth cranial nerves. Clinical manifestations, laboratory values, and treatment plans are discussed. Emergency physicians should be aware of the complications of trichloroethylene exposure and consider the diagnosis in patients with similar symptoms.

Adult↗