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Biomedical subjects

R Y Wang

Publications and source records attributed to R Y Wang.

At least 19 recordsLinked to original sources
PubMed1992

High frequency of antibodies to Mycoplasma penetrans in HIV-infected patients.

Mycoplasma penetrans, a novel mycoplasma isolated from HIV-1-infected patients with AIDS, has pathogenic properties associated with in-vivo virulence. Enzyme-linked immunosorbent assay and western blotting detected a more than 100 times higher frequency of antibodies to the mycoplasma in serum from HIV-1-infected patients with AIDS (40%) than from HIV-negative controls (0.3%). Serum from 20% of HIV-1-infected, symptom-free individuals also had M penetrans specific antibodies. The antibodies' major immunoreactivity was directed against P35 and P38, the two main lipid-associated membrane protein antigens of the organism. Patients attending sexually transmitted disease clinics had a low frequency of antibody (0.9%). None of 178 HIV-negative patients with different non-AIDS diseases, many associated with immune dysfunction and/or low white cell counts, tested positive for the antibodies. M penetrans, apparently not a commensal and not a simple opportunist, is uniquely associated with HIV-1 infection and AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1992

Spontaneous development of protective anti-T cell receptor autoimmunity targeted against a natural EAE-regulatory idiotope located within the 39-59 region of the TCR-V beta 8.2 chain.

The development of experimental autoimmune encephalomyelitis (EAE) in Lewis rats is mediated by V beta 8.2+ T cells specific for myelin basic protein. One consequence of this biased expression of V beta 8.2 is the spontaneous development of regulatory T cells and antibodies against residues 39-59 of the V beta 8.2 sequence. Moreover, a synthetic V beta 8.2-39-59 peptide could induce protection against and speed recovery from EAE. T cells and antibodies specific for V beta 8.2-39-59 could transfer protection from EAE. Recently, we reported that the protective T cell epitope is subsumed within the V beta 8-44-54 sequence. We now report that protection induced by V beta 8-44-54 lasted at least 102 days and produced "split tolerance," enhancing anti-myelin basic protein antibody titers but reducing anti-myelin basic protein T cell frequency. The shorter V beta 8-44-54 peptide induced a distinct set of antibodies that did not cross-react with the longer V beta 8.2-39-59 peptide, although both specificities could stain V beta 8.2+ T cells and were equally protective against EAE. However, the V beta 8.2-39-59 peptide, but not the V beta 8-44-54 peptide, would appear to represent the natural idiotope: antibodies to V beta 8.2-39-59 that develop spontaneously during EAE could be boosted to higher titers only by the V beta 8.2-39-59, but not by other TCR peptides from the V beta 8.2 sequence, including V beta 8-44-54 that contains the functional T cell epitope. These results suggest that natural processing of the TCR V beta-chain favors the formation of a peptide that resembles the V beta 8.2-39-59 sequence. The B cell epitope present on the V beta 8-44-54 sequence was evident only in the absence of residues 39-43 and 55-59, suggesting that the two peptides possess distinct conformations. However, the V beta 8-44-54 B cell epitope is most likely expressed on the V beta 8.2+ T cells, either as a low affinity determinant on the intact TCR alpha/beta heterodimer or as a cryptic epitope bound in the cleft of surface MHC molecules.

Amino Acid Sequence↗
PubMed1992

5-HT3 receptor antagonists fail to block the suppressant effect of cocaine on the firing rate of A10 dopamine neurons in the rat.

In the present study, we have shown that cocaine is significantly more potent in suppressing the firing rate of dopamine cells in the ventral tegmental area (VTA or A10) than in the substantia nigra pars compacta (SNC or A9). We have also determined the ability of several 5-HT3 receptor antagonists to alter the electrophysiological response of A10 dopamine neurons in the rat to cocaine, as these compounds have been implicated in modulating the effects of drugs of abuse on the dopamine system. It was found that the 5-HT3 receptor antagonists ICS205-930, zacopride and ondansetron do not alter either the firing rate or cocaine-induced suppression of the basal firing rate of A10 dopamine cells.

Animals↗
PubMed1992

The effects of prenatal cocaine exposure on spontaneously active midbrain dopamine neurons in adult male offspring: an electrophysiological study.

In this study, the technique of extracellular single unit recording was used to examine the effect of prenatal cocaine exposure on the number of spontaneously active dopamine (DA) cells in the substantia nigra pars compacta (SNC or A9) and the ventral tegmental area (VTA or A10) of male Sprague-Dawley rats on postnatal days 56-68. In addition, the effect of the direct DA receptor agonist (+/-)-apomorphine (APO) on the basal firing rate of A10 DA cells was also determined. A significant decrease in the number of spontaneously active A10 DA cells was observed in offspring whose dams were treated with 40 mg/kg/day of cocaine s.c. from gestational days 8-20 when compared with offspring of pair-fed and non-treated control dams. The number of spontaneously active A9 DA cells was significantly decreased in the offspring of cocaine-exposed dams when compared to pair-fed offspring. In contrast, there were no significant differences among the three prenatal groups regarding the sensitivity of spontaneously active A10 DA cells to APO (2-64 micrograms/kg, i.v.). Overall, our results suggest that in utero cocaine exposure may alter presynaptic DA activity in offspring long after their exposure has been terminated.

Animals↗
PubMed1992

Action of serotonin in the medial prefrontal cortex: mediation by serotonin3-like receptors.

In the present study, we investigated the effects of various serotonin (5-HT) antagonists on 5-HT's action on medial prefrontal cortical cells (mPFc) using the techniques of single cell recording and microiontophoresis. The microiontophoretic application of 5-HT (10-80 nA) produced a current-dependent suppression of mPFc cell firing and this effect was blocked by the selective 5-HT3 receptor antagonists (+/-)-zacopride, ICS 205930 and granisetron at currents of 5-20 nA. Furthermore, the intravenous (i.v.) administration of (+/-)-zacopride (5-50 micrograms/kg) markedly attenuates the suppressive action of 5-HT on mPFc cell firing. In contrast, the microiontophoresis of 5-HT1 and 5-HT2 receptor antagonists such as (+/-)-pindolol, spiperone, metergoline, and ritanserin (10-20 nA) failed to block 5-HT's effect. In fact, in some cells, spiperone and ritanserin potentiated 5-HT's action and prolonged neuronal recovery. In addition, the intravenous administration of either ritanserin (5-2,000 micrograms/kg) or metergoline (4-2,400 micrograms/kg) failed to alter 5-HT's action. The electrical stimulation of the caudal linear raphe nucleus (CLi) suppressed the spontaneous activity of 83% of the mPFc cells tested by 45 +/- 2%. This suppression was significantly attenuated by the iontophoresis of granisetron (2.5-5 nA) but not by the 5-HT2 and 5-HT1C receptor antagonist ritanserin or the relatively selective 5-HT2 receptor antagonist (+)-MDL 11,939 (10-40 nA). However, the i.v. administration of ritanserin (0.5-1.5 mg/kg) or S-zacopride (0.1 mg/kg) significantly blocked the suppression of mPFc cell firing produced by CLi stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Cocaine decreases self-control in rats: a preliminary report.

Cocaine abuse is often associated with behavior that takes into account short-term, but not long-term consequences. However, there has been no empirical research concerning the effects of cocaine on self-control (choice of a larger, more delayed reinforcer over a smaller, less delayed reinforcer). In the present research, when food-deprived rats repeatedly chose between a larger, more delayed food reinforcer and a smaller, less delayed food reinforcer, chronic intraperitoneal injections of 15 mg/kg cocaine (but not 10 mg/kg fluoxetine) decreased the rats' choices of the larger, more delayed reinforcer. Cocaine can decrease rats' self-control.

Animals↗
PubMed1992

(+/-)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane(DOI) and alpha-methyl-5-HT: 5-HT2 receptor agonistic action on phosphatidylinositol metabolism in the rat fronto-cingulate and entorhinal cortex.

In the present study, the effects of 5-HT and two 5-HT1c/5-HT2 receptor agonists, (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and alpha-methyl-serotonin (alpha-Me-5-HT) on phosphoinositide hydrolysis were compared, to determine whether DOI and alpha-Me-5-HT were full agonists. Consistent with the results obtained from previous studies, both (+/-)-DOI and alpha-Me-5-HT stimulated turnover of phosphoinositide in a concentration-dependent manner. However, the response obtained with these 5-HT1c/5-HT2 receptor agonists was only 30-40% of that of 5-HT. The stimulation of hydrolysis of phosphoinositide, produced by both 5-HT2 receptor agonists, was potently antagonized by ritanserin (a 5-HT1c/5-HT2 receptor antagonist) and alpha-phenyl-1-(2-phenylethyl)-4-piperine methanol [(+)-MDL 11,939, a 5-HT2 receptor antagonist] but not by granisetron (BRL a 5-HT3 receptor antagonist), suggesting that the action of DOI and alpha-Me-5-HT was primarily mediated by 5-HT2 receptors. When the effect of increasing the concentration of 5-HT on turnover of phosphoinositide was measured in the presence of a 1 microM concentration of the 5-HT3 receptor antagonist granisetron, the response obtained was similar to the response produced by the 5-HT2 receptor agonists, DOI and alpha-Me-5-HT. These results confirm the previous finding that 5-HT stimulates hydrolysis of phosphoinositide by interacting with 5-HT1c/5-HT2 and 5-HT3 receptors. Moreover, they suggest that DOI and alpha-Me-5-HT are full agonists at the 5-HT2 receptor, coupled to hydrolysis of phosphoinositide in the cortex of the rat.

Amphetamines↗
PubMed1992

Frequency of T cells specific for myelin basic protein and myelin proteolipid protein in blood and cerebrospinal fluid in multiple sclerosis.

T cell sensitization to two myelin components, myelin basic protein (MBP) and myelin proteolipid protein (PLP), may be important to the pathogenesis of multiple sclerosis (MS). Using the limiting dilution assay, we demonstrated that the blood of MS patients had an increased frequency of MBP-reactive T cells compared with normal subjects and patients with other neurological diseases (OND) and rheumatoid arthritis. There was no difference in T cell frequency to a synthetic peptide, PLP139-151, or Herpes simplex virus. Within cerebrospinal fluid (CSF), 37% of IL-2/IL-4-reactive T cell isolates from MS patients responded either to MBP or PLP139-151 while only 5% of similar isolates from OND patients responded to these myelin antigens. The mean relative frequency of MBP-reactive T cells within CSF from MS patients was significantly higher than that of OND patients (22 x 10(-5) cells versus 1 x 10(-5) cells) and was similar to that of MBP reactive T cells within the central nervous system of rats with experimental autoimmune encephalomyelitis. These results lend new support to the hypothesis that myelin-reactive T cells mediate disease in MS.

Amino Acid Sequence↗
PubMed1992

Effects produced by acute and chronic treatment with granisetron alone or in combination with haloperidol on midbrain dopamine neurons.

In this study, we examined the effects of acute and chronic administration of the 5-HT3 receptor antagonist granisetron (0.1, 1.0 or 10 mg/kg i.p.) alone or in combination with haloperidol (0.5 mg/kg i.p.) on the number of spontaneously active dopamine neurons in the substantia nigra pars compacta (SNC or A9) and the ventral tegmental area (VTA or A10). This was accomplished using the technique of extracellular single unit recording. Acute granisetron at 0.1 mg/kg, but not at higher doses, selectively decreased the number of spontaneously active A10 DA cells. Chronic administration of 0.1 or 1 mg/kg granisetron selectively decreased the number of spontaneously active A10 dopamine cells compared to controls, mimicking the effect produced by chronic treatment with the atypical neuroleptic drug clozapine. However, unlike the effect produced by neuroleptics, this granisetron-induced effect was not reversed by the systemic administration of apomorphine (50 micrograms/kg). These results suggest that the chronic granisetron-induced reduction of the number of spontaneous active dopamine cells is not the result of depolarization inactivation. Chronic coadministration of granisetron with haloperidol negates the effects produced by either compound alone. Acute coadministration of granisetron with haloperidol also attenuated or abolished haloperidol's action, particularly that on the A9 dopamine cells. Overall, it appears that at 0.1 and 1.0 mg/kg, chronic granisetron may possess atypical neuroleptic drug potential. However, the combination of haloperidol and granisetron nullifies changes in midbrain dopamine neurons observed with either agent alone.

Animals↗
PubMed1992

Biochemical characterization of phosphoinositide hydrolysis stimulated by 5-HT3 receptor agonists.

Serotonin (5-HT) stimulates phosphoinositide (PI) turnover in rat fronto-cingulate cortical slices and is probably mediated through the activation of both 5-HT2 and 5-HT3 receptors. We have extended these findings and have assessed whether the increased stimulation of PI turnover is secondary to 5-HT stimulated arachidonate metabolism or to the release of another neurotransmitter. Incubation of the cortical slices by the two 5-HT3 receptor agonists, 2-methyl-serotonin (2-Me-5-HT) and phenylbiguanide (PBG), significantly decreases serotonin-stimulated phosphoinositide turnover, indicating that activation of 5-HT3, receptors by 2-Me-5-HT and PBG caused the desensitized PI hydrolysis to 5-HT. Indomethacin did not affect the increased PI hydrolysis induced by 5-HT, 2-Me-5-HT and PBG, suggesting that neither cyclooxygenase nor lipoxgenase activity is required for the PI response and that it is independent of arachidonic acid metabolism. The stimulation in PI turnover induced by 5-HT and the 5-HT3 receptor agonists was not potentiated by proteinase inhibitors suggesting that the release of a peptide neurotransmitter is not involved in the PI response. In addition, the effects of 5-HT, 2-Me-5-HT and PBG on PI turnover are additive to the effect of KCl and veratrine. In conclusion, our results indicate that the action of 2-Me-5-HT and PBG on PI turnover is direct.

Animals↗
PubMed1992

Mycoplasma penetrans sp. nov., from the urogenital tract of patients with AIDS.

An unusual mycoplasma, which was isolated from the urine of a human immunodeficiency virus-positive male homosexual patient, has an elongated flask shape and two unique sharply divided internal compartments. The tiplike compartment is densely packed with fine granules, and the body compartment is loosely filled with coarse granules consistent with ribosomal structures. The organism has properties of adherence, hemadsorption, and cytadsorption and invades many different types of mammalian cells. Adhesion and penetration apparently involve the terminally located tiplike structure. Cholesterol is required for growth, and the mycoplasma ferments glucose and hydrolyzes arginine, but does not hydrolyze urea. The results of DNA homology studies revealed that this organism is not genetically related to previously described mycoplasma species that have the same biochemical properties. The results of serologic studies demonstrated that this organism is antigenically distinct from all previously described mycoplasmas. We propose that this new mollicute species should be named Mycoplasma penetrans sp. nov. The type strain is strain GTU-54-6A1 (= ATCC 55252).

Acquired Immunodeficiency Syndrome↗
PubMed1992

Selective detection of Mycoplasma fermentans by polymerase chain reaction and by using a nucleotide sequence within the insertion sequence-like element.

A new assay using the polymerase chain reaction to amplify a 206-nucleotide specific gene sequence within the insertion sequence-like element of Mycoplasma fermentans has been developed. The unique insertion sequence-like element exists in multiple copies in the M. fermentans genome. The assay selectively amplifies DNA from all strains of M. fermentans tested. In contrast, DNA from other species of human and nonhuman mycoplasmas, common tissue culture-contaminating mycoplasmas, and bacteria, as well as human, monkey, and mouse tissues do not produce the amplified DNA products specific for M. fermentans.

Animals↗
PubMed1991

The 5-HT3 receptor antagonists LY 277359 and granisetron potentiate the suppressant action of apomorphine on the basal firing rate of ventral tegmental dopamine cells.

In this study, we examined the effect of the 5-HT3 receptor antagonists LY 277359 and granisetron on the suppressant action of the dopamine receptor agonist (+/-)-apomorphine on spontaneously active dopamine cells in the substantia nigra pars compacta (SNC or A9) and ventral tegmentum area (VTA or A10) in the rat. This was accomplished using the standard extracellular single unit recording techniques. The i.v. administration of (+/-)-apomorphine (1-64 micrograms/kg) produced a dose-dependent suppression of the basal firing rate of spontaneously active A9 and A10 dopamine cells. The i.v. administration of LY 277359 at 0.01 and 0.1 mg/kg, but not 1 or 10 mg/kg, potentiated the suppressant action of (+/-)-apomorphine on A10 dopamine cell firing. In contrast, (+/-)-apomorphine's suppressant action on the firing rate of A10 dopamine neurons was potentiated by all doses of granisetron except the 10 mg/kg dose. The suppressant action of (+/-)-apomorphine in control and pretreated rats was reversed by the i.v. administration of haloperidol (0.05-0.1 mg/kg). In contrast, the suppression action of (+/-)-apomorphine on the firing rate of A9 dopamine cells was not altered by any dose of LY 277359 or granisetron. Overall, our results suggest that LY 277359 and granisetron selectively potentiate the response of A10 dopamine cells to (+/-)-apomorphine.

Animals↗
PubMed1991

The effect of acute and chronic LY 277359, a selective 5-HT3 receptor antagonist, on the number of spontaneously active midbrain dopamine neurons.

In this study, we have examined the effect of acute and chronic administration of LY 277359, a putative 5-HT3 receptor antagonist, on the number of spontaneously active dopamine cells in the substantia nigra pars compacta (SNC or A9) and ventral tegmental area (VTA or A10). This was accomplished using the standard extracellular single unit recording techniques. The acute administration of LY 277359 (0.1 or 1.0 mg/kg i.p.) produced a significant increase in the number of spontaneously active A10, but not A9, dopamine cells compared to saline controls. The acute administration of 10 mg/kg of LY 277359 did not significantly alter the number of spontaneously active dopamine cells in either area. In contrast to its acute effects, the administration of 0.1 mg/kg per day of LY 277359 for 21 days decreased the number of spontaneously active A9 and A10 dopamine cells. However, the i.v. administration of (+/-)-apomorphine (50 micrograms/kg) did not reverse LY 277359's action, suggesting that the chronic LY 277359-induced reduction of dopamine cells was not the result of depolarization block. To test whether chronic administration of LY 277359 at a high dose would induce depolarization block of dopamine cells, rats were treated with 1.0 or 10 mg/kg LY 277359. Interestingly, the chronic administration of 1.0 mg/kg LY 277359 increased the number of A10, but not A9 dopamine cells. In contrast, chronic treatment with 10 mg/kg selectively decreased the number of spontaneously active A10 dopamine cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Newly discovered mycoplasma isolated from patients infected with HIV.

Mycoplasmas have been isolated from patients with acquired immunodeficiency syndrome (AIDS) and they may contribute to the pathogenesis of this disease. We have isolated repeatedly a previously unknown mycoplasma from the urine of an HIV-positive male homosexual and, subsequently, from the urine of 5 HIV-positive patients with AIDS. The mycoplasma was not found in the urine of 98 healthy control subjects. The organism has an unusual tip-like structure with densely packed fine granules and metabolizes both glucose and arginine for growth. Antigenic and DNA analyses show the organism to be distinct from other known mycoplasmas. The mycoplasma displays in-vitro activities associated with virulence in vivo. In addition, electronmicroscopy shows that the mycoplasma can invade and attach to various human and animal cells. We are investigating whether the new mycoplasma has a role in human disease.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Location of a new encephalitogenic epitope (residues 43 to 64) in proteolipid protein that induces relapsing experimental autoimmune encephalomyelitis in PL/J and (SJL x PL)F1 mice.

Synthetic peptides of proteolipid protein (PLP) were screened for their ability to induce experimental autoimmune encephalomyelitis (EAE) in SJL/J, PL/J, and (SJL x PL)F1 mice, and T cell lines were selected by stimulation of lymph node cells with PLP peptides. PLP 141-151 was found to be less encephalitogenic in SJL/J mice than PLP 139-151, due to deletion of two amino acids from the amino-terminal end. PLP 139-151 immunization induced relapsing EAE in SJL/J and F1 mice but not PL/J mice. In contrast, PLP 43-64 induced relapsing EAE in PL/J and F1 mice but not SJL/J mice. F1 T cell lines specific for either PLP 43-64 or PLP 139-151 adoptively transferred demyelinating EAE to naive F1 recipients. Haplotypes H-2s and H-2u appear to be immunologically co-dominant in F1 mice in the PLP EAE system, which differs from the H-2u dominance in F1 mice in the myelin basic protein EAE system. The identification of a PLP peptide that is encephalitogenic in PL/J mice, in addition to the previous demonstration of PLP peptides that are encephalitogenic for SWR mice (PLP 103-116) and SJL/J mice (PLP 139-151), lends support to a role for PLP as a target Ag in autoimmune demyelinating diseases.

Amino Acid Sequence↗
PubMed1991

Protection against experimental encephalomyelitis. Idiotypic autoregulation induced by a nonencephalitogenic T cell clone expressing a cross-reactive T cell receptor V gene.

The recovery process in experimental autoimmune encephalomyelitis (EAE) in Lewis rats is characterized by an increasing diversity of T cell clones directed at secondary epitopes of myelin basic protein. Of particular interest, residues 55 to 69 of guinea pig basic protein could induce protection against EAE. A nonencephalitogenic T cell clone, C455-69, that was specific for this epitope transferred protection against both active and passive EAE. Clone C4 was found to express V beta 8.6 in its Ag receptor, and residues 39 to 59 of the TCR V beta 8.6 sequence were found to be highly crossreactive with the corresponding residues 39 to 59 of TCR V beta 8.2, which is known to induce protective anti-idiotypic T cells and antibodies. Like the TCR V beta 8.2 peptide, the V beta 8.6 sequence induced autoregulation and provided effective treatment of established EAE. Thus, the EAE-protective effect of the guinea pig basic protein 55-69 sequence was most likely mediated by T cell clones such as C4 that could efficiently induce anti-TCR immunity directed at a cross-reactive regulatory idiotope.

Animals↗