Biomedical subjects

T L Wang

Publications and source records attributed to T L Wang.

At least 37 records · Page 2Linked to original sources

PubMed1998

Morphine preconditioning attenuates neutrophil activation in rat models of myocardial infarction.

Previous results from our laboratory have suggested that morphine can attenuate neutrophil activation in patients with acute myocardial infarction. To elucidate if morphine preconditioning (PC) has the same effects via activation of neutrophil endopeptidase 24.11 (NEP), we measured serum levels of intercellular adhesion molecule-1 (ICAM-1), gp100MEL14 and NEP in adult Wistar rats subjected to ten different protocols (n = 10 for each) at baseline, immediately after and 2 h after morphine PC. All groups were subjected to 30 min of occlusion and 2 h of reperfusion. Similarly, morphine-induced PC was elicited by 3-min drug infusions (100 micrograms/kg) interspersed with 5-min drug-free periods before the prolonged 30-min occlusion. Infarct size (IS), as a percentage of the area at risk (AAR), was determined by triphenyltetrazolium staining. Pretreatment with morphine increased NEP activities (9.86 +/- 1.98 vs. 5.12 +/- 1.10 nmol/mg protein in control group; p < 0.001). Naloxone (mu-opioid receptor antagonist) (4.82 +/- 1.02 nmol/mg protein) and phosphoramidon (NEP inhibitor) (4.66 +/- 1.00 nmol/mg protein) inhibited morphine-activated NEP, whereas glibenclamide (ATP-sensitive potassium channel antagonist) and chelerythrine (protein kinase C inhibitor) had no effects. The ICAM-1 and gp100MEL14 of the third sampling were lowest for those with morphine PC (280 +/- 30 ng/ml and 2.2 +/- 0.7 micrograms/ml; p < 0.001), but naloxone (372 +/- 38 ng/ml and 3.8 +/- 0.9 micrograms/ml) and phosphoramidon (382 +/- 40 ng/ml and 4.2 +/- 1.1 micrograms/ml) abolished the above phenomenon. IS/AAR were definitely lowest for those with morphine PC (24 +/- 7%; p < 0.05). Morphine preconditioning increases NEP activities to attenuate shedding of gp100MEL14 and to ICAM-1 and, thus, provides myocardial protection.

Alkaloids↗

PubMed1998

Neurochemistry of the mammalian cone 'synaptic complex'.

UNLABELLED: The cone 'synaptic complex' is a unique structure in which a single presynaptic axon secretes glutamate onto processes of bipolar cells (both ON and OFF) and horizontal cells. In turn, the horizontal cell processes antagonize cone and bipolar responses to glutamate (probably by GABA). What still remains largely unknown is the molecular identity of the postsynaptic receptors and their exact locations. We identified several subunits of the glutamate receptor and the GABAA receptor expressed at the cone synaptic complex and localized them ultrastructurally. Glutamate receptors: (i) Invaginating (probably ON) bipolar dendrites in the monkey and rat express the metabotropic glutamate receptor, mGluR6. The stain is intense on the dendritic membrane where it first enters the invagination, and weak at the tip nearest to the ribbon. The cone membrane is electron-dense where it apposes the intense stain for mGluR6. Surprisingly, invaginating bipolar dendrites in the cat also express the AMPA receptor subunits, GluR2/3 and GluR4. (ii) Dendrites forming basal contacts in the cat (probably OFF) express the AMPA subunits GluR2/3, GluR4, and also the kainate subunit, GluR6/7. The stain is especially intense at the dendritic tips in apposition to electron-dense regions of cone membrane. (iii) Horizontal cells in the cat express the AMPA subunits GluR2/3, GluR4 and the kainate subunit, GluR6/7. The stain is strongest in the cytosol of somas and primary dendrites, but is also present in the invaginating terminals where it localizes to the membrane subjacent to the ribbon. GABAA receptors: (i) ON and OFF bipolar dendrites in the monkey express the alpha 1 and beta 2/3 subunits. The stain is localized to the bipolar cell membrane in apposition to horizontal cell processes. (ii) Cones did not express the GABAA subunits tested by immunocytochemistry, but beta 3 mRNA was amplified by RT-PCR from rat photoreceptors. CONCLUSIONS: (i) mGluR6 receptors concentrate on dendrites at the base of the invagination rather than at the apex. This implies that receptors at both 'invaginating' and 'basal' contacts lie roughly equidistant from the release sites and should therefore receive similar spatiotemporal concentrations of glutamate. (ii) The 'cone' membrane is electron-dense opposite to the receptor sites on both ON and OFF bipolar cells. This suggests a special role for this region in synaptic transmission. Possibly, these densities signify a transporter that would regulate glutamate concentration at sites remote (> 200 nm) from the locus of vesicle release.

Animals↗

PubMed1998

Sequences in the amino termini of GABA rho and GABA(A) subunits specify their selective interaction in vitro.

Molecular cloning has revealed that there are six classes of subunits capable of forming GABA-gated chloride channel receptors. GABA(A) receptors are composed of alpha, beta, gamma, delta, and epsilon/chi subunits, whereas GABA(C) receptors appear to contain rho subunits. However, retinal cells exhibiting GABA(C) responses express alpha, beta, and rho subunits, raising the possibility that GABA(C) receptors may be a mixture of subunit classes. Using in vitro translated protein, we determined that human GABA(A) receptor subunits alpha1, alpha5, and beta1 did not coimmunoprecipitate with full-length rho1, rho2, or the N-terminal domain of rho1 that contains signals for rho-subunit interaction. To explore the molecular mechanism underlying these apparently exclusive combinations, chimeric subunits were created and tested for interaction with the wild-type subunits. Transfer of the N terminus of beta1 to rho1 created a beta1rho1 chimera that coimmunoprecipitated with the alpha1 subunit but not with the rho2 subunit. Furthermore, exchanging the N terminus of the rho1 subunit with the corresponding region of beta1 produced a rho1beta1 chimera that interfered with rho1 receptor expression in Xenopus oocytes, whereas the full-length beta1 subunit had no effect. Together, these results indicate that sequences in the N termini direct assembly of rho subunits and GABA(A) subunits into GABA(C) and GABA(A) receptors, respectively.

Animals↗

PubMed1998

Mutations in the gene encoding starch synthase II profoundly alter amylopectin structure in pea embryos.

Mutations at the rug5 (rugosus5) locus have been used to elucidate the role of the major soluble isoform of starch synthase II (SSII) in amylopectin synthesis in the developing pea embryo. The SSII gene maps to the rug5 locus, and the gene in one of three rug5 mutant lines has been shown to carry a base pair substitution that introduces a stop codon into the open reading frame. All three mutant alleles cause a dramatic reduction or loss of the SSII protein. The mutations have pleiotropic effects on the activities of other isoforms of starch synthase but apparently not on those of other enzymes of starch synthesis. These mutations result in abnormal starch granule morphology and amylopectin structure. Amylopectin contains fewer chains of intermediate length (B2 and B3 chains) and more very short and very long chains than does amylopectin from wild-type embryos. The results suggest that SSII may play a specific role in the synthesis of B2 and B3 chains of amylopectin. The extent to which these findings can be extrapolated to other species is discussed.

Amylopectin↗

PubMed1997

Attenuation of neutrophil and endothelial activation by intravenous morphine in patients with acute myocardial infarction.

To investigate the effects of morphine on neutrophil and endothelial activation, we measured serum levels of intercellular adhesion molecule-1 (ICAM-1), L-selectin, and neutrophil endopeptidase 24.11 (NEP) in 38 patients with acute myocardial infarction (group 1) and 16 control subjects (group 2). In group 1, all the patients underwent blood sampling at initial presentation and 10 minutes later. Twenty of them had 3 mg of morphine administered intravenously immediately after the first sampling (group 1A) and the other 18 after a second sampling (group 1B). The serum levels of ICAM-1 and L-selectin were both significantly higher in groups 1A and 1B than in group 2. In group 1A, the ICAM-1 decreased significantly at second blood samplings (310 +/- 28 vs 368 +/- 30 ng/ml; p <0.001), whereas in group 1B there was no significant change in ICAM-1 (357 +/- 33 vs 359 +/- 26 ng/ml; p = NS). In group 1A, the L-selectin decreased significantly at second blood samplings (2.3 +/- 1.2 mg/L, p <0.001 vs baseline), whereas in group 1B there was no significant change in L-selectin (3.9 +/- 1.0 mg/L, p = NS vs baseline). There was no significant difference in baseline NEP activities between groups 1A and 1B (4.89 +/- 1.22 vs 5.14 +/- 1.57 nmol/mg protein; p = NS). However, the NEP activities at second blood samplings decreased significantly in group 1A (9.88 +/- 1.86 nmol/mg protein, p <0.001 vs baseline), whereas no significant changes were observed in group 1B (5.09 +/- 1.62 nmol/mg protein, p = NS vs baseline). In conclusion, morphine increased NEP activities and thus attenuated shedding of L-selectin and ICAM-1.

Aged↗

PubMed1997

The N-terminal domain of human GABA receptor rho1 subunits contains signals for homooligomeric and heterooligomeric interaction.

gamma-Aminobutyric acid type C (GABAC) receptors identified in retina appear to be composed of GABA rho subunits. The purpose of this study was to localize signals for homooligomeric assembly of rho1 subunits and to investigate whether the same region contained signals for heterooligomeric interaction with rho2 subunits. In vitro translated human rho1 was shown to be membrane-associated, and proteinase K susceptibility studies indicated that the N terminus was oriented in the lumen of ER-derived microsomal vesicles. This orientation suggested the involvement of the N terminus of rho1 in the initial steps of subunit assembly. To test this hypothesis, mutants were created containing only N-terminal sequences (N-rho1) or C-terminal sequences (C-rho1) of rho1. Co-immunoprecipitation studies revealed that N-rho1, but not C-rho1, interacted with rho1 in vitro. When coexpressed in Xenopus oocytes, N-rho1 interfered with rho1 receptor formation. Together, these data suggested that signals for rho1 homooligomeric assembly reside in the N-terminal half of the subunit. Sequential immunoprecipitations were then performed upon cotranslated rho1 and rho2 subunits which demonstrated that rho1 and rho2 interacted in vitro. Co-immunoprecipitation indicated that N-rho1 specifically associated with rho2. Therefore, the N-terminal regions of rho subunits contain the initial signals for both homooligomeric and heterooligomeric assembly into receptors with GABAC properties.

Animals↗

PubMed1997

A 100 amino acid region in the GABA rho 1 subunit confers robust homo-oligomeric expression.

Retinal gamma-aminobutyric acid type C (GABAC) receptors are believed to be composed of rho subunits. Although rho 1 and rho 2 are over 80% similar, the whole-cell currents generated by rho 1 receptors in Xenopus oocytes are significantly greater than those generated by rho 2 receptors. In this study, chimeric subunits containing different portions of human rho 1 and human rho 2 were created to localize sequences facilitating robust rho 1 expression. Our results indicate that these sequences reside in a 100 amino acid domain in the N-terminus of rho 1, and may involve N-linked glycosylation. Since the N-terminus also contains subunit assembly signals, rho 1 receptors may be formed more efficiently than rho 2 receptors. Therefore, this study furthers our understanding of the molecular basis of GABA-mediated inhibition in the retina.

Amino Acid Sequence↗

PubMed1997

Abnormal circadian blood pressure changes in patients with acute cerebrovascular disorders.

The central neural mechanisms of circadian rhythm are well known in animal models but less so in humans. In this study we looked for correlations between abnormalities of circadian rhythm and the sites of stroke, with the aim of identifying the location regulating the circadian rhythm in humans. We investigated the circadian profiles of arterial pressure in 100 stroke patients by ambulatory blood pressure monitoring within 2 days after their first stroke. Patients also underwent brain computed tomography and measurements of plasma norepinephrine and adrenal hormones. A total of 52 patients (group A) had abnormal patterns of circadian blood pressure rhythm while 48 patients had normal patterns (group N). The risk of an abnormal 24-hour blood pressure pattern was strongly inversely correlated with the distance between the lesion and the hypothalamus. There was also a close positive correlation between the distance from the lesion to the hypothalamus and the circadian indices of arterial blood pressure (systolic and diastolic pressure) in both groups. Abnormal circadian changes in adrenal hormones were found in 30 of 52 patients in group A, and in nine of 48 patients in group N. Apparently, the circadian rhythm of blood pressure is modulated mainly by direct neural effects and partly by the hormonal effects of the hypothalamus and its associated neural pathways. Individualized antihypertensive treatment and additional monitoring for possible cardiac events should be performed for those at a high risk of autonomic dysfunction.

Acute Disease↗

PubMed1996

The moss, Physcomitrella patens, transformed with apoaequorin cDNA responds to cold shock, mechanical perturbation and pH with transient increases in cytoplasmic calcium.

The gene for apoaequorin has been used previously to indicate cytosolic calcium changes in higher plants. Here we report the transformation of the moss Physcomitrella patens with the cDNA for apoaequorin. Stable transformants were obtained in the wild type which reconstitute the calcium-sensitive luminescent protein aequorin in vivo after incubation in coelenterazine, and continue to grow normally. The wild type responds to cold-shock (0-10 degrees C) with increases in cytosolic calcium. Mechanical perturbation, in the form of touch, also induces transient increases in cytosolic calcium. A smaller response to pH, distinct from the touch response and exhibiting different kinetics, can also be detected.

Aequorin↗

PubMed1996

Case report and review of disseminated histoplasmosis in South-East Asia: clinical and epidemiological implications.

The South-East Asian region is not known to be a major endemic area for histoplasmosis. We have recently diagnosed several cases of disseminated histoplasmosis in patients from this region. We report on a well documented indigenous case of disseminated histoplasmosis in a 62-year-old poultry farmer and review the literature for other reported cases of clinical histoplasmosis in the South-East Asian region. Sporadic cases of indigenous chronic pulmonary and non-meningeal disseminated histoplasmosis in immunocompetent hosts have been reported as well as examples of disseminated histoplasmosis in immunocompromised hosts. These reports suggest that histoplasmosis is endemic to certain areas in South-East Asia and that there may be a large number of undiagnosed and subclinical cases. The recent advances in diagnostic tests for histoplasmosis are also reviewed with reference to the experience of using these tests in the reported case.

Amphotericin B↗

PubMed1996

Extraskeletal Ewing's sarcoma presenting with pulmonary embolism.

Small round cell tumours with the morphologic characteristics of Ewing's sarcoma arise rarely in soft tissues of the extremities, retroperitoneum, chest and orbit. Patients usually present with symptoms arising from the swelling at the primary site. We report on a patient with a retroperitoneal extraskeletal Ewing's sarcoma who presented with massive tumour embolism to the pulmonary vasculature. To our knowledge, this is the first report of extraskeletal Ewing's sarcoma presenting with pulmonary tumour embolism.

Adult↗

PubMed1996

The mechanism of sympathovagal imbalance in patients with myocardial ischemia.

To investigate the mechanism of sympathovagal imbalance due to myocardial ischemia, we studied 42 consecutive patients undergoing successful percutaneous transluminal coronary angioplasty by correlating frequency domain and time domain measures of heart rate variability with parameters such as echocardiography, stress thallium scanning and radionuclide angiography before, immediately after and 2 months after the procedure. Of these, 20 patients (Group N) had normal and 22 patients (Group A) had abnormal regional wall motion. A control group of 20 healthy subjects (Group C) underwent echocardiography and examination of heart rate variability twice at 2-month intervals to check for spontaneous variations. At baseline, frequency domain measures such as low and high frequency power and time domain measures such as SDANN index (the mean of the standard deviations of the average of RR intervals) were lower in Group A than in Groups N and C, whereas no differences were detectable in ultra low and very low frequency, total power, SDNN index (the mean of the standard deviations of the mean of normal RR intervals), and r-MSSD (the root mean square of successive RR differences). There was high association between the diastolic wall stress index and both high frequency (r = -0.82) and low frequency power (r = -0.77). There were similar findings for the systolic wall stress index (r = -0.72 for high frequency and r = -0.64 for low frequency power). After successful coronary angioplasty, regional wall motion, left ventricular wall stress indices and all measures of heart rate variability were unchanged in Group N. In Group A the mean summed segment score improved from 15.9 +/- 2.6 to 12.2 +/- 1.7 (p < 0.0001), and mean low frequency, mean high frequency power (logarithmic units), and SDANN index (msec) increased from 6.10 +/- 0.23 to 6.36 +/- 0.28 (p < 0.005), from 5.36 +/- to 0.40 to 5.70 +/- 0.39 (p < 0.01) and from 70 +/- 18 to 83 +/- 18 (p < 0.01) respectively. In addition, low and high frequency power and SDANN index, lower at baseline in Group A than in the other two groups, were comparable in the three groups after coronary angioplasty. The evolution of diastolic and systolic wall stress indices paralleled that of the above three parameters. In conclusion, diastolic and systolic wall stress indices, in addition to segmental left ventricular dysfunction, were synergistically involved in determining sympathovagal imbalance in patients with significant coronary artery disease; the reversal of left ventricular dysfunction and wall stress indices improves the profile of heart rate variability. Alterations in cardiac geometry and wall stress influence mainly the discharge of afferent sympathetic and efferent parasympathetic innervations and also principally the long-term heart rate variations instead of short-term modulation.

Angioplasty, Balloon, Coronary↗

PubMed1996

The cause-effect relationship of sympathovagal activity and the outcome of percutaneous transluminal coronary angioplasty.

We studied 25 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) to determine the association of sympathovagal imbalance and the outcome of coronary angioplasty. We examined the profiles of heart rate variability (HRV) using echocardiography, stress thallium scanning and radionuclide angiography before, immediately after and 1 month after the procedure. Coronary angiography was followed up at 6 months or if restenosis was suspected, to determine whether restenosis had occurred. Frequency domain (LF/HF) and time domain (SDNN, SDANN-ind, and r-MSSD) parameters were analyzed. According to the evolution of each parameter, we classified the patients into Group Ax (improved in HRV profile) and Group Bx (deteriorated in HRV profile) [x = 1 for LF/HF, 2 for SDNN, 3 for SDANN-ind, and 4 for r-MSSD]. We found that there was no definite association between Gensini score and HRV profiles at the baseline for each group. No significant changes existed between the HRV profiles before and immediately after PTCA. For the LF/HF ratio, 5 of 11 in Group B1 had restenosis while 0 of 14 in Group B2 and 1 of 19 in Group A2 had restenosis (p < 0.01). There were no significant predictive values for SDANN-ind and r-MSSD (p = 0.12 and 0.07, respectively). We conclude that the sympathovagal imbalance did not reflect the severity in coronary artery disease but was associated with restenosis after successful PTCA.

Aged↗

PubMed1996

Measuring quality of life in different cultures: translation of the Functional Living Index for Cancer (FLIC) into Chinese and Malay in Singapore.

Quality-of-life assessment has become an accepted method of evaluation in clinical medicine. The technique is based on a patient's self-assessment of physical, psychological, and social function, as well as the effects of distressing physical symptoms. The most important aspect of quality-of-life assessment is that it brings into focus a patient-centred view of health outcome, which is broader than the physiologic measures which predominate in Western medicine. Strategies for the development and use of assessment questionnaires have evolved over the past 15 years, and numerous questionnaires have been created. Most originate in Western societies, with English as the most common language of development. Adapting such questionnaires for use in other language and cultural settings is an imprecise practice. Language translation and equivalent cultural meaning must both be addressed. This paper reports on the language translation process and results for the Functional Living Index for Cancer (FLIC) as translated into Chinese and Malay in Singapore. We employed a step-wise process beginning with translation/back translation, followed by structured pilot field trials and population sampling. Taped versions of the questionnaire were devised to meet illiteracy problems in the sample population. Paired comparisons of the Chinese and Malay versions of individual questions with their English counterparts show good correlations and similar means most of the time. Factor analysis on a population sample of 246 (112 Chinese, 35 Malay and 98 English speaking) with cancers of minimal, extensive or palliative extent is convergent with that obtained on a North American population. However, a separate analysis of the Chinese questionnaires showed some differences in factor pattern. Specific language and cultural translation difficulties are discussed. Of note is the predicted significant decrease in total FLIC scores with extent of disease within each of the language preference populations, which provides some evidence for the validity for each language version in the Singapore culture(s). Thus, the FLIC translations into Malay and Chinese in Singapore can be considered for use in local trials, subject to ongoing evaluation.

Activities of Daily Living↗

PubMed1996

Diagnostic and biological implications of mel-CAM expression in mesenchymal neoplasms.

Mel-CAM (previously MUC18) is an integral membrane glycoprotein involved in heterophilic intercellular adhesions. Mel-CAM is expressed specifically in certain normal mesenchymal tissues, including smooth muscle, endothelium, and Schwann cells. As a member of the immunoglobulin supergene family of cell adhesion molecules (CAMs), Mel-CAM may play a pivotal role in the normal differentiation and functional activity of these tissues. To determine the distribution of Mel-CAM in mesenchymal neoplasms and to investigate its potential role as a factor in tumor progression, we evaluated a spectrum of mesenchymal neoplasms by immunohistochemistry using a Mel-CAM-specific polyclonal antibody on formalin-fixed tissues. Mel-CAM positivity was observed in 5 (100%) of 5 leiomyomas, 29 (91%) of 32 leiomyosarcomas, 5 (100%) of 5 hemangiomas, 5 (100%) of 5 angiosarcomas, 3 (100%) of 3 Kaposi's sarcomas, 8 (100%) of 8 schwannomas, 10 (100%) of 10 neurofibromas, 0 (0%) of 8 malignant peripheral nerve sheath tumors, 2 (15%) of 13 malignant fibrous histiocytomas, 0 (0%) of 8 fibrosarcomas, 0 (0%) of 7 synovial sarcomas, and 0 (0%) of 6 liposarcomas. These results show that Mel-CAM is expressed consistently in neoplasms of smooth muscle and vascular origin, and that immunostaining for Mel-CAM may serve as a useful adjunct in differentiating leiomyosarcomas, angiosarcomas, and Kaposi's sarcomas from other spindle cell neoplasms. Furthermore, the observation that Mel-CAM is expressed consistently in schwannomas and neurofibromas but not in malignant peripheral nerve sheath tumors implicates Mel-CAM as a potential modulator of malignant transformation in peripheral nerve tumors.

Antigens, CD↗

PubMed1995

A single amino acid in gamma-aminobutyric acid rho 1 receptors affects competitive and noncompetitive components of picrotoxin inhibition.

A class of bicuculline-insensitive gamma-aminobutyric acid (GABA) receptors, GABAC, has been identified in retina. Several lines of evidence indicate that GABAC receptors are formed partially or wholly of GABA rho subunits. These receptors generate a Cl- current in response to GABA but differ from GABAA receptors in a number of ways. Picrotoxin, widely accepted as a noncompetitive antagonist of GABAA receptors, displays competitive and noncompetitive antagonism of GABAC receptors in perch and bovine retina and GABA rho 1 receptors expressed in Xenopus oocytes. The aim of this study was to identify the molecular basis of the two components of picrotoxin inhibition of GABA rho 1 receptors. By using a domain-swapping and mutagenesis strategy, a difference in picrotoxin sensitivity between rho 1 and rho 2 receptors was localized to a single amino acid in the putative second transmembrane domain. Substitution of this amino acid with residues found in the analogous position in highly picrotoxin-sensitive glycine alpha and GABAA subunits increased the sensitivity of rho 1 mutants 10- to 500-fold. Importantly, the competitive component of picrotoxin inhibition of the rho 1 mutant receptors was almost eliminated. These findings demonstrate that an amino acid in the putative channel domain of GABA rho 1 receptors influences picrotoxin sensitivity and mediates agonist binding by an allosteric mechanism.

Animals↗

PubMed1995

Alterations with age of the T3-stimulated release of atrial natriuretic peptide and its effect on water and sodium metabolism in rats.

The influence of age on urinary excretion of sodium and water and in vitro release of atrial natriuretic peptide (ANP) were studied in rats. Older rats had increased daily water intake and urine output. They also had increased plasma ANP, decreased right atrial contents of ANP and increased ANP release in response to 10 nM T3. The ageing process may have altered the regulatory mechanisms of water metabolism and secretion of ANP.

Aging↗

PubMed1995

Cloning and expression of two brain-specific inwardly rectifying potassium channels.

We have cloned two inwardly rectifying K+ channels that occur selectively in neurons in the brain and are designated BIRK (brain inwardly rectifying K+) channels. BIRK1 mRNA is extremely abundant and is enriched in specific brainstem nuclei, BIRK1 displays a consensus phosphate-binding loop, and expression in Xenopus oocytes has shown that its conductance is inhibited by ATP and adenosine 5'-[gamma-thio]triphosphate. BIRK2 is far less abundant and is selectively localized in telencephalic neurons. BIRK2 has a consensus sequence for cAMP-dependent phosphorylation.

Adenosine Triphosphate↗