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Biomedical subjects

S Y Wang

Publications and source records attributed to S Y Wang.

At least 19 recordsLinked to original sources

Structure of the gene and its retinoic acid-regulatory region for murine J6 serpin. An F9 teratocarcinoma cell retinoic acid-inducible protein.

We have recently reported a protein sequence deduced from the retinoic acid (RA)-inducible mRNA J6 as a novel serine protease inhibitor (serpin). In this study we have reported that the J6 serpin gene is 7.7 kilobases in length and consists of five exons with an additional option. Comparison of the organization of the J6 gene and other serpin genes reveals that the structure of the J6 gene is different from the reported four serpin gene groups. Nonetheless, intron B of the J6 gene and members of the alpha-antitrypsin gene group are at the equivalent positions, suggesting that the J6 gene is more closely related to the members of alpha-anti-trypsin gene group than other serpins. To identify the RA response region, we have further examined the nucleotide sequence of the 1-kilobase 5'-flanking region of the J6 gene. The DNA sequence from position -1050 to -738 is essential for the gene activation by RA as revealed by the stable transfection experiments. Within this region, present are four GA-GATAG motifs which are the known binding sites for GATA transcription factor family. Interestingly, there is a potential heat shock element with alternate arrays of blocks XGAAX and XTTCX spanning from -88 to -59, indicating that the J6 gene perhaps is heat-inducible.

Amino Acid Sequence

Heparin-like activity in porcine follicular fluid and rat granulosa cells.

Heparin-like activity is present in rat and porcine follicular fluids, as determined by measuring the acceleration of the inactivation of purified human thrombin by antithrombin III. The heparin-like activity is dose-dependent and specific to follicular fluid proteoglycans. Cartilage proteoglycans do not exhibit this activity at any of the concentrations tested. The activity of these macromolecules resides in the polysaccharide unit. Destruction of the protein core of the follicular fluid proteoglycans by alkaline borohydride treatment does not interfere with the "heparin-like" effect, whereas it is completely destroyed by digestion with purified heparinase. Incubation with chondroitinases has no effect. Granulosa cells which are the source of follicular fluid proteoglycans express biologically active heparin-like mucopolysaccharides. These molecules are produced under gonadotropin regulation and are associated with the cell surface material.

Animals

Identification of RBK1 potassium channels in C6 astrocytoma cells.

Ionic currents in C6 astrocytoma cells were studied using the patch clamp technique under the whole cell configuration. A delayed rectifier K+ current with an amplitude of approximately 1 nA at +50 mV was observed in 86% (92/107) of the cells examined. This K+ current resembled the delayed rectifier present in type-1 and type-2 astrocytes in vitro and could be inhibited by a variety of K+ channel blockers, including TEA (IC50:0.5 mM), 4-aminopyridine (IC50:0.2 mM), MCD peptide (IC50:52 nM), dendrotoxin I (IC50:9 nM), and charybdotoxin (74% inhibition at 50 nM). Northern blot analysis, cloning of cDNA and subsequent sequencing showed that the C6 cell delayed rectifier K+ channel is equivalent to the RBK1 K+ channel derived from a rat brain cDNA library. The level of RBK1 transcripts in C6 cells was comparable to that reported in rat brain. The C6 delayed rectifier K+ channel is probably a homomeric RBK1 K+ channel judging from its pharmacological properties which are similar to the RBK1 channel expressed in Xenopus oocytes. Some C6 cells also expressed a transiently activated outward K+ current (IA). This current was found in less than 50% of the cells and in general contributed no more than 8% of the total outward current. No voltage-dependent inward Na+ or Ca2+ currents or inwardly rectifying K+ currents were observed in over 100 C6 cells examined. The present results show that the dominant voltage gated ionic current in C6 cells is the RBK1 delayed rectifier K+ channel.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Major histocompatibility complex (MHC) class II restriction, lymphokine production, and IgE regulation of house dust mite-specific T-cell clones.

To elucidate the regulatory mechanism of human IgE synthesis, we have cloned house dust mite (Dermatophagoides pteronyssinus; Dp)-specific T-cell clones from three asthmatic children and three healthy individuals. Twelve clones were cloned from each group. All of these clones were CD3+, CD4+, CD8-, and HLA-DR+. After stimulation with allergen in the presence of antigen presenting cells (APCs), half of the T-cell clones from asthmatic children and one-third of those from normals produced interleukin 4 (IL-4). None of the patients' clones produced interferon gamma (IFN-gamma), while 10 of 12 normals' clones did. After stimulation with calcium ionophore A23187 and phorbol myristic acetate (PMA), the production of IL-4 was markedly increased in both patients and normals. However, only 3 of the 12 patients' clones produced IFN-gamma, while all of the normals' clones did. The T-cell clones of both patients and normals produced comparable IL-2. To study the kinetics of lymphokine productions, a HLA-DRw12-restricted T-cell clone (FYD 3.1) was stimulated, respectively, with a combination of A23187 and PMA, phytohemagglutinin (PHA), or Dp antigen in the presence of APCs. Maximal IL-2 and IL-4 productions were detected 12 hr after A23187 and PMA stimulation, whereas IFN-gamma could not be detected even 36 hr after stimulation. When stimulated with PHA, the production of IFN-gamma peaked on the fourth day, but IL-4 was not detected. After stimulation with Dp antigen and APCs, IL-4 and IL-2 were detected on the second and third days, but IFN-gamma was not detected. The IgE production by autologous purified B cells in the presence of allergen or IL-4 was found to be augmented by the FYD 3.1 T-cell clones. IFN-gamma was observed to counteract the effects of the T-cell clones and IL-4. Thus, the secretory patterns of lymphokine and kinetics of lymphokine production of allergen-specific T-cell clones can be used to explore the regulatory mechanism of human IgE synthesis [corrected].

Adult

Altered stereoselectivity of cocaine and bupivacaine isomers in normal and batrachotoxin-modified Na+ channels.

The inhibitory effects of local anesthetics (LAs) of cocaine and bupivacaine optical isomers on Na+ currents were studied in clonal GH3 cells under whole-cell patch clamp conditions. At holding potential of -100 mV, all four isomers inhibited peak Na+ currents when the cell was stimulated infrequently. The dose-response curves of this tonic block of peak Na+ currents by (-)/(+) cocaine and (-)/(+) bupivacaine were well fitted by the Langmuir isotherm, suggesting that one LA isomer blocked one Na+ channel. Each pair of isomers showed no greater than a twofold difference in stereoselectivity toward Na+ channels. Additional block of Na+ currents occurred when the cell was stimulated at 2 Hz. This use-dependent block was also observed in all four isomers, which again displayed little stereoselectivity. The voltage dependence of the use-dependent block produced by cocaine isomers did not overlap with the activation of Na+ channels but did overlap with the steady-state inactivation (h infinity), indicating that cocaine can bind directly to the inactivated state of Na+ channels before channel opening. In comparison, the peak batrachotoxin (BTX)-modified Na+ currents were little inhibited by cocaine and bupivacaine isomers. However, the maintained BTX-modified Na+ currents were highly sensitive toward the (-) form of cocaine and bupivacaine isomers during a prolonged depolarization. As a result, a profound time-dependent block of BTX-modified Na+ currents was evident in the presence of these LA isomers. The estimated values of the equilibrium dissociation constant (KD in micromolar) at +50 mV were 35.8, 661, 7.0, and 222 for (-)/(+) cocaine and (-)/(+) bupivacaine, respectively. Although chloramine-T (CT) also modified the fast inactivation of Na+ channels and gave rise to a maintained Na+ current during a prolonged depolarization, LA isomers showed no greater stereoselectivity in blocking this maintained current than in blocking the normal transient Na+ current. We conclude that (a) cocaine and bupivacaine isomers exhibit only weak stereoselectivity toward the LA receptor in normal and CT-treated Na+ channels, (b) BTX drastically modifies the configuration of the LA binding site so that the LA stereoselectivity of the open Na+ channels is altered by an order of magnitude, and (c) the (-) forms of cocaine and bupivacaine interact strongly with the open state of BTX-modified Na+ channels but only weakly, if at all, with the closed state. The last finding may explain why most LA drugs were reported to be less effective toward BTX-modified Na+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)

Batrachotoxins

Inactivation of batrachotoxin-modified Na+ channels in GH3 cells. Characterization and pharmacological modification.

Batrachotoxin (BTX)-modified Na+ currents were characterized in GH3 cells with a reversed Na+ gradient under whole-cell voltage clamp conditions. BTX shifts the threshold of Na+ channel activation by approximately 40 mV in the hyperpolarizing direction and nearly eliminates the declining phase of Na+ currents at all voltages, suggesting that Na+ channel inactivation is removed. Paradoxically, the steady-state inactivation (h infinity) of BTX-modified Na+ channels as determined by a two-pulse protocol shows that inactivation is still present and occurs maximally near -70 mV. About 45% of BTX-modified Na+ channels are inactivated at this voltage. The development of inactivation follows a sum of two exponential functions with tau d(fast) = 10 ms and tau d(slow) = 125 ms at -70 mV. Recovery from inactivation can be achieved after hyperpolarizing the membrane to voltages more negative than -120 mV. The time course of recovery is best described by a sum of two exponentials with tau r(fast) = 6.0 ms and tau r(slow) = 240 ms at -170 mV. After reaching a minimum at -70 mV, the h infinity curve of BTX-modified Na+ channels turns upward to reach a constant plateau value of approximately 0.9 at voltages above 0 mV. Evidently, the inactivated, BTX-modified Na+ channels can be forced open at more positive potentials. The reopening kinetics of the inactivated channels follows a single exponential with a time constant of 160 ms at +50 mV. Both chloramine-T (at 0.5 mM) and alpha-scorpion toxin (at 200 nM) diminish the inactivation of BTX-modified Na+ channels. In contrast, benzocaine at 1 mM drastically enhances the inactivation of BTX-modified Na+ channels. The h infinity curve reaches minimum of less than 0.1 at -70 mV, indicating that benzocaine binds preferentially with inactivated, BTX-modified Na+ channels. Together, these results imply that BTX-modified Na+ channels are governed by an inactivation process.

Batrachotoxins

Bone marrow transplantation for severe aplastic anemia--a study of twenty-one Chinese patients in Taiwan.

A total of 21 multiply transfused patients with severe aplastic anemia (SAA) were treated with bone marrow transplantation between March 1985 and September 1990: 20 allogeneic and one syngeneic transplants. A positive response in mixed lymphocyte culture (MLC) was also noted in 7 allogeneic recipients. Pregraft conditioning included high-dose cyclophosphamide (CY) 200 mg/kg over 4 consecutive days, followed by 300 cGy total-body irradiation the day before BMT. Seventeen patients older than 14 years received additional donor buffy-coat cells infusion for 5 days posttransplant. A combination of methotrexate and cyclosporine was used for prophylaxis of graft-versus-host disease. Seventeen patients were alive with a functional graft, and Kaplan-Meier product limit estimates showed a 80.95% probability of survival at 67.7 months. There were 4 deaths: two died of primary graft failure, one from secondary rejection, and the other from chronic GVHD-related complications. Acute GVHD, grade I was noted in only one patient (5.6%). In contrast, chronic GVHD was observed in 10 out of 18 (55.6%) evaluable patients. Venoocclusive liver disease and interstitial pneumonitis were not diagnosed. Our findings indicate that the combination of CY/TBI/BC is well tolerated and results in a low incidence of graft failure/rejection in multiply transfused Chinese patients who received transplants for SAA. The MTX/CsA combination was confirmed as being remarkable in reducing the incidence and severity of acute GVHD. For patients with SAA under the age of 40, with an HLA-identical sibling, we highly recommend BMT as the treatment of choice.

Adolescent

[Inner ear damage due to hyperlipidemia in the young and old guinea pigs].

Nineteen guinea pigs of one month and 11 of 30 months were given high fat diet for 3 months to produce hyperlipidemia; 16 of them followed by 3 months' normal diet to resume blood lipid level; 27 for control. The results showed that: The serum cholesterol level of the experimental groups was markedly elevated (P < 0.01) with fatty degeneration of liver. Damages in OHC, IHC, cells of stria vascularis and few myelin sheaths of cochlear nerve were seen in all experimental animals, and the reduction of cochlear damages was not seen in those animals with blood lipid level resumed to normal. Auditory dysfunction was very marked as shown by ABR in the old animals with hyperlipidemia as compared with controls (P < 0.01).

Animals

Purification and characterization of human macrophage-derived granulomonopoietic enhancing factor (GM-EF).

A granulomonopoietic enhancing factor (GM-EF) capable of promoting the effect of colony-stimulating factors (CSFs) on myeloid progenitor cells has been purified to homogeneity from serum-free medium conditioned by fully mature human macrophages. GM-EF was a glycoprotein with an apparent molecular weight of 74 kd and an isoelectric point of 5.2-5.3. The purified protein was heat stable (75 degrees C for 30 min) and was sensitive to treatment with trypsin, papain, and bacterial protease but not to neuraminidase. The activity of GM-EF could be effectively neutralized by GM-EF-specific antiserum, and no antigenic cross-reactivity was observed using antisera against interleukin (IL)-1, IL-4, and IL-6. These results suggest that GM-EF is a unique cytokine that is different biochemically and antigenically from other hematopoietic enhancing factors such as IL-1, IL-4, and IL-6.

Epitopes

Heterogeneity of human blood monocyte: two subpopulations with different sizes, phenotypes and functions.

Human blood mononuclear cells from normal adults were collected after density-cut centrifugation and monocytes were then isolated by removal of lymphocytes using the techniques of E-rosetting and cell adhesion. The purified monocytes were further analysed by velocity sedimentation, and two distinct subpopulations with different cell sizes were obtained. The larger monocytes were 17.0 +/- 1.8 microns in diameter with a mean sedimentation rate (SR) of 7.0 +/- 0.6 mm/hr, while the smaller monocytes were 9.5 +/- 0.8 microns in size and 4.1 +/- 0.2 mm/hr in SR. The population ratio of larger:smaller cells was approximately 2:1 (66 +/- 2.8%:34 +/- 1.6%). Both cell populations exhibited a high positive rate (> 98%) in both the non-specific esterase and the peroxidase stain. However, the larger cells had much higher phagocytic activity than the smaller ones. Furthermore, the expression of monocyte-associated antigens was also different between these two subpopulations. Thus, while most of the larger monocytes (98%) could be recognized by monoclonal antibodies MY7 and OKM1, only some (35 and 61%, respectively) of the smaller monocytes could react with those antibodies. In addition, the larger monocytes secreted a significant amount of monokines including interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2) and their production increased in proportion to the level of stimulation by bacterial lipopolysaccharide (LPS), whereas the production of monokines by the smaller monocytes remained at low levels and did not respond to LPS stimulation. These results reveal the existence of phenotypic and functional heterogeneity in human blood monocytes.

Adult

Protective effect of puerarin against myocardial reperfusion injury. Myocardial metabolism and ultrastructure.

To ascertain the beneficial effect of puerarin on the myocardium against reperfusion injury, studies on myocardial metabolism and ultrastructure were made. Twelve dogs divided into two equal groups were placed on moderate hypothermic cardiopulmonary bypass, and their hearts were subjected to 140 minutes cold cardioplegic arrest and 60 minute reperfusion. In the control group, the hearts were perfused with crystalloid cardioplegic solution (CPS) every 20 minutes during arrest. In the treated group, the hearts received CPS containing puerarin (2 mg/kg). Myocardial oxygen consumption, lactate production, creatine phosphokinase (CPK) release, water content and ultrastructural alterations were determined before ischemia, during cardiac arrest and at reperfusion. The results showed that intermittent infusion of CPS containing puerarin significantly decreased myocardial lactate production during ischemia, as well as myocardial oxygen consumption, CPK release and water content during reperfusion. Under electronmicroscopy, the degree of ischemic damage judged by a scoring method was less pronounced in the puerarin group than in the control. The authors conclude that puerarin has protective effects on the function of hearts that have undergone long periods of arrest and reperfusion.

Animals

[Schizophrenia and factitious cheilitis: a case report].

Factitious Cheilitis is a rare skin disorder which has been seen in patients with emotional disturbances, particularly in cases with neurotic and personality disorders. However, there have been no reports of factitious cheilitis seen in cases of schizophrenia. This study reports on a case of schizophrenic disorder, where the patient was observed to develop factitious cheilitis whilst subject to unstable psychiatric conditions. The case reported here is of a 59 year-old female widow, who has experienced the delusion of being controlled, the delusion of being possessed. Been subject to auditory hallucination and vague somatic pain for eight years and had a very poor psychotropic drug compliance. Observation revealed frequent licking of the lips unrelated to drug-induced dyskinesia, but as a possibly linked response to hallucination whilst subject to an intense unstable emotional and painful state. Factitious cheilitis was proved with biopsy of the lips and pathological findings of acanthosis, hyperkeratosis and parakeratosis. After psychiatric and dermatologic care, her cheilitic condition improved. This study demonstrates that factitious cheilitis can be seen in a schizophrenic patient, specifically where hallucination and emotional instability coupled with long-term licking of the lips can result in factitious cheilitis. The relationship of skin disorder and psychiatric illness is discussed.

Cheilitis

[Low social economic status family and child maltreatment].

The purpose of the present research was to develop child abuse potential inventories as a screening tool. The sample was 248 families who were all financially supported by Chinese Children's Fund. Kaohsiung Family Helper. One of the inventories selected, that was translated into Chinese by the expert committee, was the Child Abuse Potential Inventory developed by Milner. The internal consistency and test-retest reliabilities obtained by this research were as good as Milner's and basic interpretation of four factors was found to be was consistent with Milner's data. The other inventory developed by the expert committee was the Child Abuse Potential Interview used by social workers to interview caretakers. Having completed the questionnaire social workers rated 15 items, i.e. immaturity, lack of parenting skills, unrealistic expectancy, social isolation, unresolved affective needs, abused experiences, crisis, substance abuse etc. The coefficients of correlation between these two inventories were 0.20-0.37, respectively, which indicated that these inventories assessed abuse potential trait and uniqueness. Therefore, these inventories were considered both highly applicable.

Adolescent

[A study about the desirable characteristics of the qualified physicians: the application of Delphi method].

The purpose of this study is to adapt the Delphi Study method in establishing a consensus of good doctor characteristics from a panel of department heads (N = 22) at four medical colleges in Taiwan within three given categories: 1. professional knowledge and techniques; 2. attitudes and standards; and 3. interpersonal relationship. In this study three rounds of questionnaires were administered to the panel to extract their opinions regarding the characteristics of good doctoring. 76 items of good doctoring characteristics were solicited from the department heads at four medical colleges to the opening questionnaire. The conclusive results indicated that 15 of these 58 items were ranked as the most important characteristics by panel members. The findings from this investigation will help facilitate the decision making process of officials regarding innovation in the training of good doctor. Moreover, the conclusions could be included in developing and planning of instruments for the future doctor evaluation methods.

Clinical Competence

The protective effect of puerarin against myocardial reperfusion injury. Study on cardiac function.

In order to find out if puerarin could protect the hearts from myocardial reperfusion injury after cardiac arrest, twelve dogs divided into two equal groups were placed on moderately hypothermic cardiopulmonary bypass and their hearts were subjected to 140 min of cold cardioplegic arrest and 60 min of reperfusion. In the control group, the hearts were perfused with a crystalloid cardioplegic solution (CPS) through the aortic root every 20 min during arrest. In the treated group, the hearts received CPS containing puerarin (2 mg/kg). Cardiac hemodynamic variables were monitored throughout the experiments. Left ventricular function curves were formed before ischemia and after 60 min of reperfusion. The results showed that the recovery of left ventricular function in the treated group was significantly better than that in the controls (81 +/- 11% versus 39 +/- 7%, P less than 0.01). Compared with preischemic values, the increase of coronary blood flow (CBF) at cardiac arrest in the puerarin-treated group was higher than that in the control group (214 +/- 11 versus 177 +/- 4 ml/min, P less than 0.01). The data indicate that puerarin has protective effects on the cardiac function after prolonged arrest and reperfusion.

Animals

Women's perceptions of caesarian delivery.

A Perception of Caesarian Delivery Scale that measured the incidence and severity of perceptions and feelings in response to recent Caesarian delivery was administered to 60 mothers who had had Caesarian sections. The scores obtained from this scale were analyzed by factor analysis to determine the relationships within categories of responses, and were analyzed by one-way ANOVA to measure any variation among different demographic groups. A reliability coefficient of 0.93 was obtained for this scale. Factor analysis of the quantitative data defined four categories of women's perceptions associated with Caesarian delivery. Each of the four categories were labeled and discussed. However, there were no significant differences in factor scores between groups with different parities, types of anesthesia, and types of Caesarian section.

Adult

Inhibition of microtubule assembly is a possible mechanism of action of mitoxantrone.

We have found that mitoxantrone can inhibit the polymerization of brain tubulin in a dose dependent manner. MXT had relatively high affinity for tubulin but had no appreciable effect on tubulin associated guanosine-triphosphatase (GTPase) activity nor could it compete with vinblastine (VB) and colchicine (Col) for tubulin binding sites. Furthermore, MXT (0.1-10 microM) is antiproliferative to cold-treated (0 degree C) epithelial cells after only brief exposure (30 min). These results indicated that MXT is a microtubule inhibitory agent and can exert its anticellular effect through modulation of microtubule assembly.

Animals