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Biomedical subjects

J L Tang

Publications and source records attributed to J L Tang.

At least 73 records · Page 4Linked to original sources
PubMed1996

Transcriptional regulation of endothelial constitutive PGHS-1 expression by phorbol ester.

Human endothelial cells contain two isoforms of prostaglandin H synthase (PGHS). PGHS-1 is constitutively expressed, whereas PGHS-2 is inducible. To determine whether expression of PGHS-1 is regulated, we treated cultured human umbilical vein endothelial cells (HUVEC) with phorbol 12-myristate 13-acetate (PMA) or its inactive analogue and measured PGHS-1 mRNA levels by Northern analysis and competitive polymerase chain reaction. PMA increased PGHS-1 mRNA levels determined by both techniques in a time- and concentration-dependent manner. The mRNA level was increased about twofold over the basal level after 4-6 h of PMA (10-50 nM) treatment. The level of PGHS-1 protein was similarly increased by PMA. Stimulation of PGHS-1 mRNA levels was abrogated by cycloheximide, actinomycin D, staurosporine, or calphostin C. The 5'-promoter activity of human PGHS-1 gene was increased twofold over the basal level by PMA in NS-20 cells. These results indicate that the constitutive PGHS-1 in HUVEC is transcriptionally stimulated by PMA in a protein kinase C-dependent manner.

Base Sequence↗
PubMed1996

[Determination of azathiopurine concentration in human serum by second derivative spectra method].

A sensitive and rapid method for the determination of azathiopurine concentration in human serum was established. By using ultraviolet second derivative spectra, the method eliminated background interference of biological sample and coexisting drugs. The serum sample was extracted with ethyl acetate, the extract was evaporated to dryness with a gentle N2 stream, and 0.25 ml of methanol was added to dissolve the residue. Quantitative calculation was made with analytical wavelength of 274 nm and 293 nm, and peak- to- valley method. The minimum detectable concentration of AZP in serum was 25 ng.ml-1 and average recovery was 99.3% +/- 5.9%.

Azathioprine↗
PubMed1995

Mortality in relation to tar yield of cigarettes: a prospective study of four cohorts.

OBJECTIVE: To investigate relation between tar yield of manufactured cigarettes and mortality from smoking related diseases. DESIGN: Prospective epidemiological study of four cohorts of men studied between 1967 and 1982. SETTING: Combined data from British United Provident Association (BUPA) study (London), Whitehall study (London), Paisley-Renfrew study (Scotland), and United Kingdom heart disease prevention project (England and Wales). SUBJECTS: Of the 56,255 men aged over 35 who were included in the studies, 2742 deaths occurred among 12,400 smokers. Average follow up was 13 years. MAIN OUTCOME MEASURES: Relative mortality from smoking related diseases according to tar yields of cigarettes smoked. RESULTS: Age adjusted mortality from smoking related diseases in smokers of filter cigarettes was 9% lower (95% confidence interval 1% to 17%) than in smokers related diseases consistently decreased with decreasing tar yield. Relative mortality in cigarette smokers for a 15 mg decrease in tar yield per cigarette was 0.75 (0.52 to 1.09) for lung cancer, 0.77 (0.61 to 0.97) for coronary heart disease, 0.86 (0.50 to 1.50) for stroke, 0.78 (0.40 to 1.48) for chronic obstructive lung diseases, 0.78 (0.65 to 0.93) for these smoking related diseases combined, and 0.77 (0.65 to 0.90) for all smoking related diseases. CONCLUSION: About a quarter of deaths from lung cancer, coronary heart disease, and possibly other smoking related diseases would have been avoided by lowering tar yield from 30 mg per cigarette to 15 mg. Reducing cigarette tar yields in Britain has had a modest effect in reducing smoking related mortality.

Adult↗
PubMed1995

An analysis of the effectiveness of interventions intended to help people stop smoking.

In a systematic review of the efficacy of interventions intended to help people stop smoking, data have been analyzed from 188 randomized controlled trials. Following personal advice and encouragement to stop smoking given by physicians during a single routine consultation, an estimated 2% (95% confidence limits, 1%, 3%; P < .001) of all smokers stopped smoking and did not relapse up to 1 year as a direct consequence of the advice. The effect is modest but cost-effective: the cost of saving a life is about $1500. Supplementary interventions (follow-up letters or visits, demonstration of spirometry, etc) have an additional effect--variable in extent. Advice and encouragement are particularly effective for smokers at special risk--pregnant women (efficacy; 8%) and patients with ischemic heart disease. Behavior modification techniques (relaxation, rewards and punishment, avoiding "trigger" situations, etc), in group or individual sessions led by a psychologist, have an effect that is statistically significant (P = .05) but no greater than simple advice by a physician (2%); yet, these techniques are several times more expensive. The effect of hypnosis is unproved (no trials have used biochemical markers). Nicotine replacement therapy is effective in an estimated 13% of smokers who seek help in cessation; the effect is greater in those who are nicotine-dependent. Other pharmacological treatments are not of proven efficacy, and acupuncture is ineffective. Sudden cessation or gradual reduction in smoking are similar in their efficacy on average. Physicians should take time to advise all their patients who smoke to quit. Smokers who are intent on stopping should be given additional support and encouraged to use nicotine replacement therapy.

Cost-Benefit Analysis↗
PubMed1995

Role of Sp1 in transcriptional activation of human nitric oxide synthase type III gene.

Endothelial nitric oxide synthase (eNOS or NOS-III) is constitutively expressed. To elucidate the mechanism by which the basal expression of NOS-III gene is activated, we constructed in a luciferase vector, pXP1, serial 5'-deletion mutants of a 1.3-kb 5'-flanking fragment and transiently expressed them in cultured human endothelial cells. The promotor activity was detected in the -198/+22 region which contains several putative Sp1 binding sites. DNase I footprinting assays coupled with gel shift assays revealed the GC box(-104/-90) to be the Sp1 binding site. Site-directed mutation of 4 crucial bases in this site reduced the promotor activity by > 90%. These findings provide strong evidence that binding of Sp1 or closely related protein to this site is required for the activation of basal NOS-III transcription.

Amino Acid Oxidoreductases↗
PubMed1995

Transcriptional induction of endothelial nitric oxide synthase type III by lysophosphatidylcholine.

Endothelial synthesis of NO is catalyzed by constitutive NO synthase type III (NOS-III). NOS-III has been thought to be regulated mainly at the level of enzyme activity by intracellular calcium. We report that in human umbilical vein endothelial cells lysophosphatidylcholine (lyso-PC), a component of atherogenic lipoproteins and atherosclerotic lesions, increases NOS-III mRNA and protein levels. This leads to the augmentation of NOS-III activity and the enhancement of antiplatelet properties of endothelial cells. Importantly, nuclear run-off experiments demonstrate a transcriptional mechanism of regulation of NOS-III expression by lysophosphatidylcholine. As endothelium-derived NO appears to be an anti-atherogenic molecule, induction of NOS-III by lyso-PC may be a protective response that limits the progress of the atherosclerotic lesion and promotes its regression.

Amino Acid Oxidoreductases↗
PubMed1995

Detection of dural involvement by magnetic resonance imaging in adult patients with acute leukemias--preliminary experience.

Retrospectively, the dura in 18 adult patients with acute leukemia were evaluated by gadolinium-enhanced T1-weighted magnetic resonance imaging (MRI). Abnormal dural enhancements were detected in three of four patients with positive cerebrospinal fluid (CSF) cytology, in one of five with suspicious central nervous system (CNS) disease, and in two of nine asymptomatic patients. Computed tomography failed to demonstrate any dural abnormality in these six patients. The abnormal dural enhancement was found in either (a) the brain and the spine, (b) the thoracolumbar spine, or (c) the area adjacent to the parenchymal lesions. Three of the patients were in hematological remission stage; disappearance of the abnormal dural enhancement was observed 1-2 months after radiotherapy and high-dose systemic chemotherapy. The results suggest that MRI is a sensitive and noninvasive imaging modality and superior to CT in detecting dural disease in leukemic patients.

Adolescent↗
PubMed1995

Long-term disease-free survival after autologous bone marrow transplantation in a primary plasma cell leukaemia: detection of minimal residual disease in the transplant marrow by third-complementarity-determining region-specific probes.

Primary plasma cell leukaemia (PPCL) is a rare form of plasma cell neoplasm. Treatments of PPCL have been most disappointing. A patient with PPCL received high-dose melphalan plus total body irradiation and autologous bone marrow transplantation (ABMT). By using third-complementarity-determining region (CDRIII)-specific probes, minimal residual disease (MRD) was detected in remission marrow, collected 1 month before ABMT. MRD was no longer detected by CDRIII-specific probes 6, 19 and 26 months after transplantation. The patient remained in complete remission up to 59 months after ABMT.

Adult↗
PubMed1994

How effective is nicotine replacement therapy in helping people to stop smoking?

OBJECTIVE: To assess the efficacy of nicotine replacement therapy in helping people to stop smoking. DESIGN: Analysis of the results of 28 randomised trials of nicotine 2 mg chewing gum, six trials of nicotine 4 mg chewing gum, and six trials of nicotine transdermal patch. SUBJECTS AND SETTING: Subjects were self referred (responding to advertisements or attending anti-smoking clinics) in 20 trials and invited (general practice or hospital patients) in 20. Therapists in self referred trials were generally experienced in helping people stop smoking but not in invited trials. MAIN OUTCOME MEASURE: Efficacy was defined as difference in percentages of treated and control subjects who had stopped smoking at one year. RESULTS: Efficacy was highly significant (P < 0.001) for both gum and patch. Nicotine 2 mg chewing gum had an overall efficacy of 6% (95% confidence interval 4% to 8%), greater in self referred subjects than in invited subjects (11% v 3%). Efficacy depended on the extent of dependence on nicotine as assessed by a simple questionnaire; it was 16% (7% to 25%) in "high dependence" smokers, but in "low dependence" smokers there was no significant effect. The 4 mg gum was effective in about one third of "high dependence" smokers. The efficacy of the nicotine patch (9% (6% to 13%) overall) was less strongly related to nicotine dependence, perhaps because the patch cannot deliver a bolus of nicotine to satisfy craving. CONCLUSIONS: Both gum and patch are effective aids to help nicotine dependent smokers who seek help in stopping. Among the most highly nicotine dependent smokers (those craving a cigarette on waking) the 4 mg gum is the most effective form of replacement therapy; it could enable one third to stop. In less highly dependent smokers the different preparations are comparable in their efficacy but the patch offers greater convenience and minimal need for instruction in its use. Overall, nicotine replacement therapy could enable about 15% of smokers who seek help in stopping smoking to give up the habit.

Administration, Cutaneous↗
PubMed1994

Bone marrow transplantation in Taiwan: an overview.

In Taiwan, a country with 21 million people, 388 bone marrow transplants (BMTs), 308 allografts and 80 autografts, were performed in 5 BMT centers from November 1983 to October 1993. The commonest indications were leukemia, aplastic anemia, lymphoma and thalassemia. Campaigns promoting an unrelated marrow donor registry were started in August 1993 and recruited approximately 26,000 volunteers. A peripheral stem cell program is just beginning. The overall results of BMT in Taiwan are comparable to other countries. The complications of BMT are similar to Western series, except that acute GVHD was rarer in one large series; this observation needs further study. A particular indication for allogeneic BMT in Taiwan is thalassemia, accounting for 10% of all patients. Disease-free survival after BMT for thalassemia is 44%; graft rejection is the major cause of treatment failure. Another important issue is the role of hepatitis B virus (HBV) in BMT, since the prevalence of HBV infection in Taiwan is very high (> 90%). Abnormal liver function is currently the most common complication and might be related to HBV. Among nearly 100 allogeneic BMTs with HBV carriers as either donor or recipient, 2 patients (approximately 2%) died of HBV-related hepatic failure. Whether the HBV status of the donor and recipient is an important prognostic factor remains to be defined.

Anemia, Aplastic↗
PubMed1994

Severe isolated acute hepatic graft-versus-host disease with vanishing bile duct syndrome.

A 28-year-old man with chronic myelogenous leukaemia in blastic transformation underwent allogeneic bone marrow transplantation from his HLA-identical brother. Severe, progressive cholestatic jaundice developed from day 25 and did not respond to repeated therapy with high-dose methylprednisolone. In addition to marked cholestasis, both liver biopsy (day 69) and autopsy (day 134) findings revealed total disappearance of interlobular bile ducts in all of the portal areas, although extrahepatic manifestations of GVHD were minimal. Isolated acute vanishing bile duct syndrome can occur as the most severe form of acute hepatic GVHD.

Acute Disease↗
PubMed1993

Delta-9-tetrahydrocannabinol-(THC)-mediated inhibition of macrophage macromolecular metabolism is antagonized by human serum proteins and by cell surface proteins.

Our previous study demonstrated THC-inhibited DNA synthesis and the phagocytic activity of P388D1 cells [Tang, Lancz, Specter & Bullock (1992) Int. J. Immunopharmac., 14, 253-262]. The ability of proteins in human and bovine sera and of constitutive cellular proteins to modulate the biologic activity of THC was investigated. Both human and fetal bovine sera antagonized a THC-mediated inhibition of P388D1 cell DNA synthesis in a dose-dependent manner. This antagonism was proportional to the protein concentration present in the medium. Both albumin and gamma-globulins influenced THC's inhibitory effects, although they were less potent alpha/beta serum lipoproteins. Exclusion of fatty acid moieties from the albumin did not diminish its ability to antagonize THC. Tritium-labeled THC was acid precipitable only after incubation with bovine or human serum albumin but not DNA, suggesting a physical interaction between the cannabinoid and the protein. Further studies showed that pre-treating cells with trypsin to remove surface proteins significantly enhanced the inhibitory activity of sub-toxic concentrations of THC. Thus, the data indicate that the magnitude of THC's biological effects is determined by the presence and concentration of soluble proteins in the microenvironment and by constitutive proteins present on the cell surface.

Animals↗
PubMed1992

Marijuana and immunity: tetrahydrocannabinol-mediated inhibition of growth and phagocytic activity of the murine macrophage cell line, P388D1.

The effects of delta-9-tetrahydrocannabinol (THC) on the growth, DNA synthesis and phagocytic activity of P388D1, a murine macrophage cell line, were investigated. Incubating cell cultures with THC resulted in a dose-dependent inhibition of cell propagation and DNA synthesis. The magnitude of these effects was dependent upon the number of cells in the culture as well as the protein content in the culture medium. As the cell number increased, the THC effect decreased. Using cell cultures in which the cell concentration was standardized, THC (greater than or equal to 5 micrograms/ml) produced pronounced inhibitions of cell growth and DNA synthesis, while lower THC concentrations (less than or equal to 3 micrograms/ml) were less effective. Studies examining the phagocytic activity of the P388D1 cells indicating exposure to THC (5 micrograms/ml for 2 h) only marginally affected the association of latex beads with the external surface of the plasma membrane. However, the ability of these THC-treated cells to internalize the latex particles was severely depressed. Thus, the data indicate that THC inhibited the growth and functional activity of murine macrophages in vitro and suggests that the P388D1 cell line is a useful model to study the effects of cannabinoids on the phagocytic process.

Animals↗
PubMed1992

Inactivation of the retinoblastoma gene in acute myelogenous leukaemia.

To investigate the role of retinoblastoma susceptibility (RB) gene inactivation in leukaemogenesis, we evaluated 36 bone marrow specimens of acute leukaemia for RB protein expression by immunoprecipitation and Western blot analysis. 15 patients had no detectable RB protein at initial screening. However, nine of them were subsequently excluded due to evidence of protein degradation. Of 27 valid cases, six (22%) were repeatedly shown to lack expression of the RB protein with three different anti-RB antibodies. Five were patients with acute myelogenous leukaemia (AML) and one, mixed-lineage acute leukaemia. The RB inactivation was noted more frequently in AML (5/18, 28%) than in acute lymphoid leukaemia (0/7, 0%). By karyotyping, none of these six patients exhibited cytogenetic changes involving chromosome 13q14, the RB locus. There is no correlation between inactivation of the RB gene and FAB subtypes or cytogenetic changes. Four patients achieved complete remission with standard chemotherapy for 6, 12, 20 and 26+ months, respectively. Southern and Northern blot analyses further indicated that the RB genes were grossly intact and the level of RB transcripts did not decrease in the majority of these six patients. These results suggest that the absence of RB products in some of acute leukaemia might be regulated at the post-transcriptional level, and it imposes no significant effect on treatment response and prognosis.

Adolescent↗
PubMed1992

Successful treatment of cytomegalovirus pneumonitis with ganciclovir and high-dose intravenous immunoglobulin in a bone marrow transplant recipient.

A 35-year-old man with acute lymphoblastic leukemia in second remission received an allogeneic bone marrow transplant from an HLA-compatible sibling donor. Unfortunately, cytomegalovirus (CMV) pneumonitis was histologically documented on Day +72. Combination therapy with ganciclovir (9-[2-hydroxy-1-(hydroxy-methyl) ethoxymethyl] guanine) and high-dose intravenous immunoglobulin (IVIG) was started immediately. The treatment comprised a three-week induction course (ganciclovir, 2.5 mg/kg q8h and IVIG, 500 mg/kg qod) and a seven-week fixed-dose maintenance course (ganciclovir 5 mg/kg thrice a week for 20 doses and IVIG 500 mg/kg twice a week for eight doses). The pneumonia resolved gradually, and he was free from symptoms within two weeks. The only significant side effect was moderately severe myelosuppression which was reversible after discontinuation of ganciclovir. The patient had a relapse of leukemia on Day +186, but there was no recurrence of CMV pneumonitis. This result confirms that such combination therapy is effective in the treatment of CMV pneumonitis in a patient with a bone marrow transplant.

Adult↗