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Biomedical subjects

T L Wang

Publications and source records attributed to T L Wang.

At least 73 records · Page 4Linked to original sources

GABA rho 2 receptor pharmacological profile: GABA recognition site similarities to rho 1.

The rho 2 receptor for gamma-aminobutyric acid (GABA) induces GABA-gated currents when expressed as a homooligomer in Xenopus oocytes. rho 2 responses display pharmacological profiles similar to those of expressed rho 1 receptors, although responses were slower, most agonists were more potent at rho 2 and Im values for the partial agonist imidazole-4-acetic acid were 7-fold higher. Amino acids important for most aspects of GABA agonist ligand recognition may not be among those that differ between rho 1 and rho 2, including the 20% amino acid difference in the N-terminal region.

Animals↗

Regulation of fibronectin and laminin binding activity in cultured human lymphoblastic cell lines.

The current study shows that a clonal derivative of the Jurkat cell line up-regulates both the avidity and density of the alpha 6/beta 1 receptor in response to phorbol 12-myristate 13-acetate (PMA). This derivative attaches to fibronectin and, to a lesser degree, laminin constitutively. Adhesion and spreading are dramatically up-regulated following treatment with PMA. The response on fibronectin peaks within 4 hours, is insensitive to cyclohexamide, can be blocked by monoclonal antibodies (Mabs) to the beta 1 and alpha 5 subunits of the beta 1 family of integrins, and is not associated with increased expression of the alpha 5 or beta 1 epitopes at the cell surface. In contrast, the response on laminin is biphasic. The early phase parallels the response on fibronectin. The second phase peaks after 48-72 hours of treatment with PMA, is sensitive to cycloheximide, can be blocked by Mabs to the beta 1 and alpha 6 subunits, and is associated with increased expression of the alpha 6 epitope. Both the density independent and dependent responses to PMA in Jurkat cells are blocked by the protein kinase inhibitor staurosporine. The HSB-2, CEM, Molt-4, and HPB-ALL T-lymphoblastic cell lines also up-regulate attachment to fibronectin and laminin following treatment with PMA. All four lines constitutively attach to fibronectin and show rapid up-regulation of attachment following treatment with PMA. None of the lines attach to laminin prior to PMA treatment; however, specific adhesion developed after 4-120 hours of treatment. The most mature lines (Jurkat and HPB-ALL) up-regulated adhesion on laminin more rapidly than the less phenotypically mature lines (CEM, Molt-4, and HSB-2). In summary, clonal derivatives of the Jurkat cell line up-regulated attachment to laminin through protein kinase dependent increases in alpha 6/beta 1 receptor avidity and density. In addition, the expression of functional receptors for laminin is linked to developmental maturity in a series of T-lymphoblastic cell lines.

Alkaloids↗

Increased concentrations of atrial and plasma atrial natriuretic peptide in castrated male rats.

The effects of orchiectomy and testosterone replacement on the plasma concentration and the atrial stores of atrial natriuretic peptide (ANP) were studied in the rats. Male rats were orchiectomized (Orc) three weeks before replacement with testosterone propionate (TP, 20 mg/ml/kg body weight) or sesame oil for five days. Immunoreactive ANP (IR-ANP) in the extracted right atria and plasma of experimental rats was measured. Plasma ANP concentrations were 206 +/- 22, 927 +/- 151, and 264 +/- 61 pg/ml in normal control, Orc, and Orc + TP rats, respectively. ANP contents in right atria were higher in Orc (108 +/- 9 ng/mg tissue) and TP-treated Orc rats (123 +/- 9 ng/mg tissue) than in normal animals (32 +/- 7 ng/mg tissue). These results indicate an increased plasma concentration and atrial stores in the castrated male rats. Replacement of testosterone in the castrated male rats does not decrease the atrial ANP stores, but decreases the plasma ANP concentration.

Animals↗

Detection of intra-atrial conduit leakage by transesophageal echocardiography.

A 19-year-old male patient who had undergone total cavo-pulmonary connection for complex congenital cyanotic heart disease with partial anomalous pulmonary venous return, was found to have persistent postoperative cyanosis. Transesophageal echocardiography disclosed leakage of the intra-atrial Gortex conduit with a right-to-left shunt. Prompt re-do operation confirmed the site of the leakage which was successfully repaired. Intraoperative transesophageal echocardiography may be indicated so as to avoid a secondary open-chest procedure for this complication.

Adult↗

Expression of myb-related genes in the moss, Physcomitrella patens.

Three cDNA clones encoding proteins containing a myb-related DNA binding domain have been isolated from a cDNA library prepared from protonemal tissue of the moss, Physcomitrella patens. The three cDNA clones between them encode two different classes of myb-like proteins, termed Pp1 and Pp2, that, outside of the myb domain, show no regions of significant homology. Acidic domains, capable of forming alpha-helical structures, are present in the carboxy-termini of the derived amino acid sequences from Pp1 and Pp2cDNAs suggesting that, like other myb genes, these proteins probably function as transcriptional activators. In contrast to other plants, where extensive myb-related gene families are present in the genome, a relatively small family is present in P. patens. Analyses of transcript levels during development of P. patens showed that maximum levels of transcription of the two genes occurred in young wild-type protonemal tissue that correlated with the time of maximum mitotic index. A decline in the expression of both genes occurs with increasing age of the wild-type tissue. Aberrant levels of expression of the two genes were observed in developmental mutants of P. patens which, as well as carrying specific morphological mutations, have greatly retarded protonemal growth rates. Transformation of wild-type P. patens with antisense constructs derived from Pp1 and Pp2 cDNA clones led to a dramatically reduced frequency of transformants when the expression of the reporter gene within the constructs was selected. Taken together, the data strongly suggest that expression of Pp1 and Pp2 is essential for cell growth during normal gametophytic development of P. patens.

Amino Acid Sequence↗

Acute deep vein thrombosis in hospital practice.

A recent cross sectional study on symptomatic acute deep vein thrombosis at the National University Hospital (NUH) in Singapore found a frequency rate of 0.79 per 1000 patient admissions. A total of 39 patients were accrued over 18 months, 36 with deep vein thrombosis alone and three complicated by pulmonary embolism. No sex or ethnic predilection was observed in this cohort of hospitalised patients. Twenty-eight (71.8%) patients were 40 years or older. Majority (89.7%) of patients had at least two predisposing factors. While prolonged bedrest and operative procedures featured equally frequently in patients above and below 40 years, neoplasms were predominantly associated with the former and protein C or S deficiency primarily with the latter. The exhaustive laboratory confirmation of an inherent thrombotic tendency is recommended only for patients below 40 years of age.

Acute Disease↗

HTLV-1 associated T cell lymphoma in South East Asia: case report and family study.

Geographic clustering of human T cell lymphoma/leukaemia virus type 1 (HTLV-1) infection is well recognised, particularly in south western Japan, parts of West and Central Africa, the south eastern United States and the Caribbean islands. Sporadic cases have been reported in many other parts of the world. The first case of HTLV-1 associated leukaemia/lymphoma (ATLL) in South East Asia is reported. Contact tracing showed a high incidence of carriers among the relatives.

Carrier State↗

Interleukin-1 inhibits cholesterol side-chain cleavage cytochrome P450 expression in primary cultures of Leydig cells.

Interleukin-1 (IL-1) is a potent inhibitor of Leydig cell function. We have reported that IL-1 inhibited hCG-induced cAMP and testosterone formation. In the present study we evaluated the effect of IL-1 on Leydig cell cholesterol side-chain cleavage cytochrome P450 (P450scc) mRNA levels. P450scc is the rate-limiting enzyme for Leydig cell steroidogenesis. Highly purified Leydig cells were prepared from adult Sprague-Dawley male rats (55-65 day-old) using the combination of elutriation and Percoll gradient. Purified Leydig cells were then cultured with or without IL-1 beta (1-100 ng/ml) and recombinant human monocyte-derived IL-1 receptor antagonist (250 ng/ml) for 24 h. hCG (10 ng/ml), 8-bromo-cAMP (0.1 mM), or 4 beta-phorbol 12 beta-myristate 13 alpha-acetate was then added, and cultures were continued for an additional 6 h. P450scc mRNA levels of Leydig cells were very low to undetectable after 24 h in culture and could be stimulated by the addition of either hCG (10 ng/ml) or 8-bromo-cAMP (0.1 mM), but the addition of 4 beta-phorbol 12 beta-myristate 13 alpha-acetate had no effect. P450scc mRNA levels increased as early as 2 h after the addition of hCG. Furthermore, cycloheximide (1 microgram/ml) markedly blocked hCG-induced P450scc mRNA expression. This indicates that synthesis of a labile new protein(s) is required for the induction of P450scc mRNA by hCG. IL-1 beta inhibited hCG-stimulated testosterone formation and P450scc mRNA expression in a dose-dependent manner. The inhibitory effects of IL-1 beta could be reversed by the concomitant addition of IL-1 receptor antagonist. Our results suggest that P450scc mRNA levels of Leydig cells are modulated by IL-1. This may be one mechanism that could explain the inhibitory effects of IL-1 on Leydig cell steroidogenesis.

8-Bromo Cyclic Adenosine Monophosphate↗

Hepatocellular carcinoma--a case series of 104 patients.

The records of one hundred and four patients with confirmed hepatocellular carcinoma seen over a two year period at the National University Hospital were analysed to elucidate the clinical features of our local patients and to assess their response to various therapeutic modalities. Chinese males were over-represented with a peak frequency in the sixth to eighth decade of life. Seventy-five percent of the patients were HBsAg positive and at least 88% had evidence of previous Hepatitis B infection. Ninety-one percent were symptomatic at presentation with pain being the most common symptom. Hepatomegaly with features of cirrhosis were the main physical findings. Seventy percent of the patients presented within three months after the onset of symptoms. The majority of patients had stage II or III disease at diagnosis. Twenty percent of patients had normal alpha-fetoprotein levels. Chemotherapy did not appear to show a survival benefit. Curative surgical resection was feasible in about 10% of patients and it remains the only chance for long term survival. There is an urgent need to identify more effective drugs or other modalities to treat this common and rapidly fatal malignancy. Identification of high risk patients should prompt screening with both serum alpha-fetoprotein and ultrasonography of the liver.

Adolescent↗

Cisplatin and 5-fluorouracil continuous infusion for metastatic nasopharyngeal carcinoma.

The activity of cisplatin and a 120-hour continuous infusion of 5-fluorouracil (5-FU) was evaluated in 25 patients with metastatic nasopharyngeal carcinoma. Cisplatin 100 mg/m2 and 5-FU 1000 mg/m2/day by continuous infusion for 120 hours were given via an implanted venous access device and ambulatory infusion pump. Eighteen (72%) patients had multiple sites of metastases and seven (28%) patients had only bony metastases. Subjective responses in terms of pain relief and improvement in performance status were seen in 21 (84%) patients. Overall objective response was seen in 19 (76%) patients with two complete remissions (CR) and 17 partial remissions (PR). Locoregional disease responded more completely and rapidly than bony or visceral metastases. Toxicities included nausea, vomiting, neuropathy and one septic death. Cisplatin and 5-FU by continuous infusion represent an effective treatment for metastatic nasopharyngeal carcinoma.

Adult↗

A non-fatal case report of acute fatty liver of pregnancy.

Acute fatty liver of pregnancy (AFLP) is a potentially fatal disorder that typically complicates the third trimester of pregnancy. Unrecognised, acute fatty liver of pregnancy may rapidly progress to fulminant hepatic failure, disseminated intravascular coagulation, acute renal failure and death. The outcome is highly favourable, with complete hepatic recovery, if the diagnosis is made early and pregnancy terminated promptly. The diagnostic criteria of AFLP are met if third trimester jaundice is associated with hyperuricaemia, the presence of nucleated red blood cells in the peripheral blood film and hepatic attenuation values consistent with fatty infiltration by at least one imaging technique. We report here a 38 year old Chinese woman with acute fatty liver of pregnancy, a non-fatal case complicated by extrahepatic manifestations of disseminated intravascular coagulation, haemorrhage and renal dysfunction.

Acute Disease↗

Developmental genetic studies of the moss, Physcomitrella patens.

The development of the haploid gametophyte stage of Physcomitrella patens presents excellent opportunities for the detailed study of plant morphogenesis at the cellular level. The filamentous protonema undergoes a number of developmental transitions that can be observed directly in living material using time-lapse video microscopy and that can be manipulated both by treatment with phytohormones and by environmental stimuli. Mutants affecting these processes can be isolated and can be analysed using conventional as well as parasexual methods. Molecular biological techniques are now being established since these will be essential if the mechanisms that bring about morphogenetic processes are to be understood at the molecular level. A technique for genetic transformation has been devised and is being exploited to attempt to tag developmentally-relevant genes using maize transposons. Changes in gene activity associated with developmental transitions and in response to treatment with phytohormones and environmental stimuli are being studied using cDNA library subtraction techniques. Heterologous genes involved in the control of transcription and of the cell cycle are being used to probe the P. patens genome to identify possible homologues involved in developmental regulation.

Cytokinins↗

Prognostic usefulness of cytogenetic analysis for haematological malignancies--two case reports on acute myeloid leukaemia.

Since the setup of marrow cytogenetic analysis at the National University Hospital (NUH) of Singapore in 1988, we have systematically examined all patients with haematological neoplasia for clonal abnormalities. In most patients, diagnosis was unequivocal on clinical and morphological grounds so that karyotyping was undertaken for prognostic purposes. Two patients are described who illustrate the prognostic implications of nonrandom chromosomal derangements. They highlight the increasing appreciation of the importance of cytogenetic analysis as an independent and reliable prognostic tool in the management of haematological malignancies.

Acute Disease↗

Storage protein gene expression is localised to regions lacking mitotic activity in developing pea embryos. An analysis of seed development in Pisum sativum XIV.

Storage protein gene expression has been studied in relation to mitotic activity to ascertain whether these processes are linked during embryo development in pea. Sections from immature pea embryos were probed by in situ hybridisation to show the pattern of vicilin storage protein gene expression. In addition, the location of mitotic cells was identified using fluorescence microscopy. Vicilin mRNA was first localised in the parenchyma cells of the upper adaxial region of the cotyledons. As the embryos increased in fresh weight, gene expression spread from this region, in a wave-like manner, down and across the cotyledons. The gene was only expressed in those regions of the embryo that lacked mitotic activity.

Fabaceae↗

[45Ca-uptake, mitochondrial protein bound Ca2+ and ultrastructural distribution of Ca2+ in some brain regions of mice during drug-induced analgesia].

After buprenorphine (Bup, 0.8 mg/kg ip) treatment 45Ca-uptake (cpm/mg fresh brain) in vivo by brain slices decreased from 589 +/- 12 and 486 +/- 12 to 522 +/- 14 and 408 +/- 10 and mitochondrial protein bound Tb3+ (Tb3+ relative fluorescent intensity) reduced from 41 +/- 5 and 32 +/- 2 to 30 +/- 3 and 22 +/- 2 in periaqueductal grey and hypothalamus, respectively. A large amount dense precipitate occurred in the myelin sheath and mitochondria in both regions. The 45Ca-uptake evoked by buprenorphine at 16 micrograms/40 microliter in vitro has the similar tendency with that in vivo. Treated by ruthenium red (20 micrograms/mouse ip or icv) before buprenorphine, the above-mentioned effects were all abolished. Similar results were obtained with morphine (Mor, 10 mg/kg ip) and verapamil (Ver, 8 micrograms/mouse icv) instead of buprenorphine and ruthenium red, respectively. These results suggest that Ca2+ transport across neuroplasmic membranes plays a mediator role in drug-induced analgesia.

Analgesics↗

Antimotility effects of Chinese herbal medicines on human sperm.

Caesalpinia sappan extract from a study of screened Chinese herbal medicines was found to be a potent agent for the inactivation of human sperm in vitro. Exposure of sperm from healthy donors to this agent showed remarkably reduced sperm motility. The antimotility effect of Caesalpinia sappan is concentration-dependent and about 2.5 mg/ml is required to reduce motility to 50% the control medium (EC50). This result suggests that this traditional Chinese herbal medicine possesses an antimotility effect on human sperm in vitro and has the potential of becoming in the future a new and acceptable male oral contraceptive.

Contraceptive Agents, Male↗

[Histological changes of the thymus in the aged].

Thymus tissues from 70 autopsy cases (aged 40-89 years) were examined. The thymic parenchyma decreased progressively corresponding with ageing and was replaced synchronously by the adipose tissue. Anyhow, the thymic tissue did not disappear completely, but became small irregular islands distributed dispersively in the fibroadipose tissue and lost its normal structure of thymic lobules and demarcation between cortex and medulla. Additionally, lymphocytes and Hassall's corpuscles were markedly decreased in number. In stress involution caused by chronic diseases, the thymic parenchyma presented further atrophic changes.

Adult↗

[Atrial natriuretic polypeptide in the human and rat spinal cord].

The widespread distribution of atrial natriuretic polypeptide (ANP) immunoreactive material was demonstrated in the human and rat spinal cord, using specific immunogold-silver staining technique and radioimmunoassay. Immunogold-silver staining studies showed that ANP immunoreactive neurons were quite prevalent in the human spinal cord. ANP immunoreactive neurons were largely found in the ventral horn and less in the dorsal and lateral horns. ANP immunoreactive material was absent with anti-ANP serum preabsorbed with ANP. In rats, radioimmunoassay demonstrated that ANP immunoreactive material was present in whole spinal cord. The highest concentration was found in the sacral spinal cord (21.9 +/- 4.48 ng/g tissue), the moderate in the lumbar (3.78 +/- 0.74 ng/g tissue) and the lowest in the cervical and thoracic (0.58 +/- 0.14 and 0.46 +/- 0.21 ng/g tissue, respectively). Gel chromatography and reverse-phase HPLC revealed multiple molecular forms in the rat spinal cord, but the main molecular form was the 28 amino acid rANP. In vivo study showed that ANP was released from the rat spinal cord by depolarizing concentration of potassium.

Animals↗