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Biomedical subjects

H Y Wang

Publications and source records attributed to H Y Wang.

At least 19 recordsLinked to original sources
PubMed1996

Vasoactive intestinal peptide inhibits IL-4 production in murine T cells by a post-transcriptional mechanism.

Vasoactive intestinal peptide (VIP), a neuropeptide present in the peptidergic innervation of lymphoid organs and expressed in thymocytes and peripheral lymphocytes, modulates cytokine expression in T lymphocytes. VIP down-regulates the expression of IL-2 and IL-10 mRNA in T cells stimulated through the TCR-associated CD3 complex. In contrast, IL-4 production is inhibited at a post-transcriptional level. In this study, we investigate the molecular mechanisms involved in the inhibition of IL-4 production by VIP. At the protein level, the time courses for IL-2 and IL-4 inhibition by VIP are different, with IL-4 being affected approximately 24 h later than IL-2. Northern blots and competitive reverse-transcription PCR analysis confirm the post-transcriptional inhibition of IL-4 production in both murine spleen cells and thymocytes activated through the CD3 complex. VIP does not affect IL-4 secretion, and does not induce a rapid IL-4 reuptake. Exogenous rIL-2 completely reverses the inhibitory effect of VIP, suggesting that VIP inhibits IL-4 production indirectly as a consequence of IL-2 inhibition. Studies regarding the newly synthesized IL-4 protein show that although VIP and exogenous IL-2 do not affect the rate of IL-4 synthesis, VIP reduces significantly the stability of the newly synthesized IL-4 protein, and exogenous IL-2 can restore it to the levels observed in activated cells in the absence of VIP. These results explore the molecular mechanisms involved in the neuroendocrine regulation of cytokine production, and support the idea that neuropeptides released or produced in the local lymphoid microenvironment may participate in the intricate cytokine network controlling local immune responses.

Animals↗
PubMed1996

Vertical distortion in distal extension ridges and palatal area of casts made by different techniques.

A coordinate measurement machine with laser probe was used to measure the vertical distortion of the casts produced by use of three types of impression materials (irreversible hydrocolloid, condensation silicone, and addition silicone) and two types of trays (stock and custom trays). Results indicated that all impression groups showed positive vertical distortion (ranging from 0.00566 to 0.30299 mm) at the edentulous ridges and palatal area. The amount of the vertical distortion was greatest at the palatal area and was followed by the high edentulous ridge and the low edentulous ridge. Addition silicone, with either custom tray or stock tray, was the most accurate impression material. Condensation silicone was more accurate than irreversible hydrocolloid in custom tray impression. However, in stock tray impression the irreversible hydrocolloid was more accurate than the condensation silicone. The results suggest that, with careful manipulation, irreversible hydrocolloid with stock tray impression may provide a satisfactory cast for fabricating the framework of a distal extension removable partial denture.

Alginates↗
PubMed1996

IL-4 function can be transferred to the IL-2 receptor by tyrosine containing sequences found in the IL-4 receptor alpha chain.

IL-4 binds to a cell surface receptor complex that consists of the IL-4 binding protein (IL-4R alpha) and the gamma chain of the IL-2 receptor complex (gamma c). The receptors for IL-4 and IL-2 have several features in common; both use the gamma c as a receptor component, and both activate the Janus kinases JAK-1 and JAK-3. In spite of these similarities, IL-4 evokes specific responses, including the tyrosine phosphorylation of 4PS/IRS-2 and the induction of CD23. To determine whether sequences within the cytoplasmic domain of the IL-4R alpha specify these IL-4-specific responses, we transplanted the insulin IL-4 receptor motif (I4R motif) of the huIL-4R alpha to the cytoplasmic domain of a truncated IL-2R beta. In addition, we transplanted a region that contains peptide sequences shown to block Stat6 binding to DNA. We analyzed the ability of cells expressing these IL-2R-IL-4R chimeric constructs to respond to IL-2. We found that IL-4 function could be transplanted to the IL-2 receptor by these regions and that proliferative and differentiative functions can be induced by different receptor sequences.

Amino Acid Sequence↗
PubMed1996

Myenteric ganglionic 5-hydroxytryptamine(1P) signal transmission is mediated via Go protein.

The role of G proteins in mediating the signal transduction of the guinea pig myenteric ganglionic 5-hydroxytryptamine (5-HT)1P receptors was examined. Stimulation of ganglionic membranes with 5-HT in the presence of [35S]GTPgammaS or [alpha 32P]GTP increased guanine nucleotide binding to G(alpha)o but not to G(alpha)s, G(alpha)i or G(alpha)q in a concentration-dependent fashion. Pertussis toxin pretreatment markedly reduce this 5-HT induced response. Similarly, the 5-HT1P receptor-mediated slowly developing and long-lasting depolarizing response is potentiated by GTPgammaS and is inhibited by GDPbetaS or pertussis toxin. The activation of G(alpha)o by 5-HT also was mimicked by the 5-HT1P agonist, 5-hydroxyindalpine and was blocked by the selective 5-HT1P antagonist, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide. These data provide compelling evidence to suggest that transmembrane signaling for the 5-HT1P receptors in isolated myenteric ganglia is transduced by the trimeric Go protein.

Animals↗
PubMed1996

The Gs alpha/Gi alpha 2 axis controls adipogenesis independently of adenylylcyclase.

Adipogenesis is the commitment of embryonic stem cells to the highly -differentiated phenotype of the adipocyte, a cell specialized to regulate, in a dynamic fashion, lipid storage. The mouse embryonic 3T3-L1 fibroblasts provide a useful model in which to probe the control differentiation in general and adipogenesis in particular. The G-proteins Gs alpha and Gi alpha 2 have been shown to modulate commitment of fibroblasts to adipocytes in response to inducers such as dexamethasone and meythylisobutylxanthine. Cellular levels of Gs alpha decline sharply in response to inducers as cells commit to the adipogenic phenotype. The molecular strategies of antisense DNA technology and expression of constitutively-activated mutants of Gi alpha 2 reveal that either suppression of Gs alpha or expression of constitutively-active Gi alpha 2 dramatically accelerate the ability of inducers to stimulate adipogenesis or act as inducers themselves. These roles of Gs alpha and Gi alpha 2 are expressed in ambient or elevated intracellular cyclic AMP, demonstrating a critical role of G-proteins in cellular differentiation independent of adenylylcyclase.

3T3 Cells↗
PubMed1995

Determination of codeine in human plasma by high-performance liquid chromatography with fluorescence detection.

A rapid, reliable and rugged assay for determining codeine in human plasma using reversed-phase high-performance liquid chromatography with fluorescence detection was developed. This analytical method utilized an ion-exchange/mixed-mode solid-phase extraction procedure. The chromatographic separation was achieved using a 150 x 4.6 mm I.D., 3-microns reversed-phase C8 (deactivated for basic analytes) column at ambient temperature. Fluorescence detection (excitation at 214 nm and emission above 345 nm) for codeine and nalorphine allowed for a detectable limit of 5 ng/ml. The results showed that the method was linear from 10 to 300 ng/ml. The method had good reproducibility, precision, accuracy and recoveries of 91 and 90% for codeine and nalorphine, respectively. This method has been applied to study the pharmacokinetics of codeine in normal human subjects.

Chromatography, High Pressure Liquid↗
PubMed1995

Buthionine sulfoximine pretreatment potentiates the effect of isolated lung perfusion with doxorubicin.

BACKGROUND: Although surgical resection remains the mainstay of treatment for metastatic pulmonary sarcoma, 5-year survival approaches only 25%. Chemotherapy has been limited by tumor resistance and systemic toxicity. We assessed the efficacy of L-buthionine-SR-sulfoximine, an inhibitor of glutathione synthesis, as a sensitizer for isolated lung perfusion. METHODS: In experiment 1, sarcoma-bearing rats (n = 20) received either buthionine sulfoximine via intraperitoneal injection or Hespan. After the last injection, tumor glutathione levels were measured. In experiment 2, rats (n = 60) were injected with sarcoma intravenously. On day 6, animals were pretreated with either buthionine sulfoximine or Hespan intraperitoneally. On day 7, rats underwent isolated lung perfusion (Hespan or doxorubicin) or intravenous therapy (Hespan or doxorubicin). On day 14, tumor nodules were counted. RESULTS: Buthionine sulfoximine effectively depleted tumor glutathione. Animals treated with intravenous therapy had no response to therapy, whereas those animals treated with doxorubicin isolated lung perfusion alone had a limited response. Buthionine-sulfoximine pretreatment in combination with doxorubicin isolated lung perfusion led to a 13-fold reduction in tumor nodules and 5 complete responses. CONCLUSIONS: Buthionine-sulfoximine pretreatment in combination with doxorubicin isolated lung perfusion is superior to intravenous doxorubicin and doxorubicin isolated lung perfusion alone for the treatment of metastatic pulmonary sarcoma.

Animals↗
PubMed1995

Pulmonary artery perfusion of doxorubicin with blood flow occlusion: pharmacokinetics and treatment in a metastatic sarcoma model.

BACKGROUND: We compared pharmacokinetics, toxicity, and treatment efficacy of pulmonary artery perfusion of low-dose doxorubicin with blood flow occlusion to intravenous doxorubicin injection in a metastatic sarcoma model in the rat. METHODS: Animals received left pulmonary artery perfusion with 0.1, 0.2, or 0.5 mg/kg doxorubicin at a rate of 0.1 mL/min for 1 minute with 20 minutes of blood flow occlusion. Doxorubicin levels of the lung, heart, and serum were assayed. Body weights after treatment were recorded and right pneumonectomy was performed. The results were compared with those in rats that received 5 mg/kg doxorubicin by intravenous injection or the saline group. Pulmonary sarcoma metastases were treated with 0.5 mg/kg doxorubicin through lung perfusion or intravenously, or with saline solution. RESULTS: Doxorubicin levels in the lung, heart, and serum were 112.1 +/- 9.2 micrograms/g, 1.7 +/- 0.2 microgram/g, and 0.3 +/- 0.1 microgram/mL in the group with 0.5 mg/kg doxorubicin perfusion, versus 24.8 +/- 1.9 microgram/g, 10.1 +/- 1.3 microgram/g, and 0.7 +/- 0.2 microgram/mL in the intravenous group (p < 0.05). Animals had normal growth patterns and survived after right pneumonectomy in the perfused group, whereas the intravenous group failed to thrive. No tumors were found or a significant reduction in nodules was noted in the lungs treated with perfusion as compared with untreated right lungs or the intravenous and saline groups. CONCLUSION: This chemotherapy model has important pharmacokinetic advantages and causes an increased treatment response for pulmonary metastatic sarcoma with minimal systemic and local toxicity as compared with systemic doxorubicin administration.

Animals↗
PubMed1995

Pulmonary metastasis of hepatocellular carcinoma associated with transarterial chemoembolization.

UNLABELLED: Recent advances in both diagnosis and treatment of hepatocellular carcinoma have improved the prognosis and changed the clinical significance of the subsequently increasing distant metastases. Pulmonary metastasis of hepatocellular carcinoma associated with transcatheter arterial chemoembolization has rarely been reported. METHODS: To evaluate whether transcatheter arterial chemoembolization increases the risk of pulmonary metastasis of hepatocellular carcinoma, 230 patients were studied. Among them, 156 received transcatheter arterial chemoembolization with an interval of 12-16 weeks, the remaining 74 cases refused transcatheter arterial chemoembolization and received only conservative treatment. All patients were followed up with chest x-ray films taken before transcatheter arterial chemoembolization, during admission or in the out-patient department. The mean follow-up interval was 3.37 +/- 1.51 months. RESULTS: Pulmonary metastasis was found in 25.6% (40/156) and 8.1% (6/74) of the patients with and without transcatheter arterial chemoembolization (p = 0.002). The median interval between initial diagnosis and pulmonary metastasis was 3.39 +/- 0.08 and 11.72 +/- 2.91 months among patients with and without transcatheter arterial chemoembolization (p = 0.001). The mean age, sex, existence of cirrhosis, severity of cirrhosis, presence of collateral arterial circulation, amount of lipiodol and agent of anti-cancer drugs were not associated with the development of lung metastasis. However, factors predisposing to lung metastasis included: solitary tumor with tumor size > 10 cm, multiple tumors with main tumor > 5 cm or diffuse hepatocellular carcinoma, intrahepatic portal vein thrombosis, arterioportal or arteriovenous shunt, and the presence of incomplete tumor necrosis after transcatheter arterial chemoembolization (especially combined with necrotic area > 50% main tumor size). CONCLUSIONS: Pulmonary metastasis associated with transcatheter arterial chemoembolization has a strong adverse impact on patient survival.

Analysis of Variance↗
PubMed1995

Enhancement of NGF gene expression in rat brain by the memory-enhancing peptide AVP(4-8).

Northern blot analysis of nerve growth factor (NGF) was used to evaluate the effect of exogenous AVP(4-8) on the transcription of NGF gene in rat brain. NGF expression was found to be significantly enhanced by exogenous AVP(4-8) in the hippocampus as well as in the cerebral cortex in a time period of 12 h. This effect was inhibited by an antagonist to AVP(4-8). In addition, gel mobility shift assay was also used to observe the in vitro expression of c-fos gene in rat hippocampal slices. Our results suggest that NGF gene is one of the target genes responsible for memory-enhancing responses induced by AVP(4-8) and that the enhancement of NGF gene expression may share the signaling pathway mediated by AVP(4-8) receptor and c-fos gene expression.

Animals↗
PubMed1995

Exercise reduces age-dependent decrease in platelet protein kinase C activity and translocation.

BACKGROUND: This study examined the effect of age and aerobic exercise performed on a regular basis on human platelet protein kinase C (PKC) activity and translocation. METHODS: Blood platelets were obtained from young (20-36 years) and older (61-78 years) healthy male human subjects. Platelets were incubated with PMA, 5-HT, or thrombin; PKC activities were measured in partially purified extracts of cytosolic and membranous fractions. RESULTS: Platelet PKC activities associated with both the membranes and the cytosol cellular fractions were significantly reduced in older nonexercisers. Redistribution of platelet PKC activity elicited by stimulating the cell surface receptors for 5-HT or thrombin or by direct PKC stimulation (PMA) was found to be reduced in the elderly subjects. Maintenance of aerobic fitness in the older group of exercisers partially prevented the age-associated decline in platelet PKC activity and in stimuli-induced enzyme redistribution. CONCLUSIONS: These results indicate that platelet PKC activity and its translocation may be biological markers of aging and that aerobic exercise may serve to slow the rate at which enzyme activation declines during senescence.

Adult↗
PubMed1995

Revised technique of isolated lung perfusion in the rat.

Isolated lung perfusion in the rat is a useful research tool. Pulmonary arteriotomy and venotomy repair is required for animal survival. Rat pulmonary vessels are fragile, thin, and small in caliber, making their repair the focal technical point. This technique has been improved. The arteriotomy now is closed with a single suture and the venotomy no longer requires repair. The lung is returned to its original anatomic position then compressed to stop bleeding. These improvements have improved animal morbidity and mortality markedly while reducing operating time.

Animals↗
PubMed1995

Prenatal exposure to cocaine selectively reduces D1 dopamine receptor-mediated activation of striatal Gs proteins.

The effect of in utero exposure to cocaine on striatal dopamine receptors was assessed at postnatal days 10 through 100 by examining receptor-mediated increases in GTP binding to G alpha proteins. Pregnant Dutch-belted rabbits were injected with 4 mg/kg i.v. of cocaine HCl twice a day on gestational days 8 through 29, and striatal membranes were prepared from their progenies on days 10 through 100. Dopamine-stimulated [35S]GTP gamma S binding to membrane alpha subunits was measured and found to increase binding to G alpha s and G alpha i. Pharmacological characterization of the dopamine response revealed that enhanced [35S]GTP gamma S binding to G alpha s is associated with D1 receptor stimulation, whereas binding to G alpha i is linked to D2 receptor activation. The abilities of dopamine to stimulate the binding of [35S]GTP gamma S to G alpha s but not to G alpha i was reduced in striata obtained from cocaine-exposed animals when examined at 10, 50 or 100 days of age. Similarly, prenatal cocaine exposure also reduced dopamine-stimulated [alpha-32P]GTP binding to G alpha s without influencing binding to G alpha i. Fetal cocaine exposure did not change carbachol-induced increases in [35S]GTP gamma S binding to G alpha i and G alpha o. Immunoblot analyses showed no changes in the amounts of these alpha subunits in membranes from cocaine-exposed animals vs. controls. Moreover, prenatal cocaine did not affect [3H]SCH23390 binding to D1 dopamine receptors in the caudate, putamen or substantia nigra.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1995

Prenatal cocaine exposure selectively reduces mesocortical dopamine release.

The effect of prenatal exposure to cocaine on the release of [3H]dopamine and on presynaptic dopamine autoreceptor regulation of [3H]dopamine release in prelabeled frontal cortical, cingulate cortical and striatal slices was investigated. The release of [3H]dopamine that is evoked by high K+ was reduced by 20 to 28% in the cortical regions but not in striatum. This effect was observed at 10 days of age and persisted up to postnatal day 120 in rabbits that were exposed to cocaine during gestational days 8 to 29. Spontaneous [3H]dopamine release was increased by 18 to 22% in frontal and cingulate cortices but not in striatum of the 10- but not the 50- or 120-day-old rabbit that was exposed to cocaine during gestational days 8 to 29. Total [3H]dopamine accumulated in brain slices examined on postnatal days 10, 50 or 120 was not affected by prenatal cocaine exposure. Incubation of slices with dopamine dose-dependently inhibited K(+)-evoked [3H]dopamine release in both cortical and striatal slices. Prenatal cocaine exposure enhanced the responsiveness to in vitro dopamine in the two cortical regions but not in striatum. Fetal cocaine exposure did not affect the levels of dopamine or its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in frontal cortex or striatum. Similarly, no apparent differences in dopamine metabolism, as indicated by the ratio of 3,4-dihydroxyphenylacetic acid + homovanillic acid/dopamine, were observed in these brain areas. These findings demonstrate that prenatal cocaine exposure selectively affects depolarization-evoked [3H]dopamine release and its regulation by presynaptic dopamine autoreceptor in cortical areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Receptor-mediated activation of G proteins is reduced in postmortem brains from Alzheimer's disease patients.

The effects of Alzheimer's disease (AD) on [35S]GTP gamma S binding to G proteins was examined in postmortem cerebrocortex. Stimulation of the beta-adrenergic or muscarinic cholinergic receptors in control tissue with selective agonists resulted in increases in [35S]GTP gamma S binding to G alpha proteins in a receptor-specific fashion. The responses were markedly reduced in brain tissues from AD patients. In contrast, basal [35S]GTP gamma S binding to the G alpha proteins was relatively intact in AD brains. Immunoblot analyses reveal that levels of cerebrocortical G alpha proteins in AD are not altered. The results suggest that in AD the decrease in agonist-stimulated [35S]GTP gamma S binding to G proteins may be a result of decoupling between receptors and their associated G proteins.

Aged↗
PubMed1994

Unilateral pulmonary artery occlusion inhibits growth of metastatic sarcoma in the rat lung.

Tumors depend on their blood supply for growth. The blood supply to metastatic neoplasia of lung is usually from the pulmonary circulation or both the pulmonary and systemic circulation. The antineoplastic effect of pulmonary artery occlusion was investigated in a rat model of methylcholanthrene-induced metastatic pulmonary sarcoma. Left pulmonary artery ligation was performed on day 7 after tumor inoculation, and animals were sacrificed on day 14. The tumor burden of the left lung decreased 44% when compared with the control group. The survival of non-tumor-bearing rats undergoing left pulmonary artery ligation for 24 hours followed by right pneumonectomy after 2 weeks was also studied. No significant lung damage after a period of left pulmonary artery ligation was seen, as evidenced by both survival after contralateral right pneumonectomy and histology. Balloon occlusion of pulmonary artery, together with regional chemotherapy for patients with lung metastases, may warrant investigation.

Animals↗
PubMed1994

Involvement of protein kinase C in the axonal growth-promoting effect on spinal cord neurons by target-derived astrocytes.

Astroglial cells participate in a variety of developmental events during neuronal morphogenesis. We have shown that axonal, but not dendritic, outgrowth of spinal cord neurons can be promoted by a diffusible factor or factors secreted from target region-derived cerebellar astroglia in vitro in comparison with spinal astroglia. In the present study, we examined the involvement of protein kinase C (PKC) in the axon-promoting effect by astroglia. The inhibition of PKC by sphingosine or by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) at high concentration greatly reduced the mean axonal length of spinal neurons cultured in medium conditioned by cerebellar astroglia (SCn-CBg), while activation of PKC by TPA at low concentration, or by retinoic acid, was not additive to the glial effect. The activation of PKC by TPA or retinoic acid promoted axon growth of spinal neurons cultured in medium conditioned by spinal astroglia (SCn-SCg), which otherwise would not be as supportive for axon growth as cerebellar astroglia. Western blotting and PKC activity assays showed that there was a trend for increased PKC activity and protein levels (in particular, PKC beta) in SCn-CBg cultures, which correlated with enhanced axon growth. Inhibition of PKC by sphingosine appeared to decrease protein levels, especially PKC beta, which correlated with suppressed axon outgrowth. In SCn-SCg cultures, phorbol ester activation of PKC increased both activity and protein levels of both PKC alpha and PKC beta. This activation correlated with stimulated axonal outgrowth. These results suggest that the glial signaling that regulates specific axonal outgrowth by target astroglia is mediated in part by the PKC second messenger system.

Animals↗