Smoking and risk of myocardial infarction. Studying relative risk is not enough.
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Adult↗
Biomedical subjects
J L Tang
Publications and source records attributed to J L Tang.
Transcriptional regulation of endothelial nitric-oxide synthase by lysophosphatidylcholine.
We have shown that lysophosphatidylcholine (lyso-PC) increases endothelial nitric-oxide synthase (eNOS) expression at the transcriptional level (Zembowicz, A., Tang, J.-L., and Wu, K. K. (1995) J. Biol. Chem. 270, 17006-17010). To elucidate the mechanism by which lyso-PC increases the eNOS transcription, we identified Sp1 sites at -104 to -90 and PEA3 sites at -40 to -24 as being involved in lyso-PC-induced promoter activity. Site-directed mutagenesis of Sp1 sites resulted in a marked reduction of basal and lyso-PC-induced activity whereas PEA3 site mutation abrogated response to lyso-PC. Band shift assays revealed that lyso-PC augmented Sp1 binding activity. Pretreatment of cells or nuclear extracts with okadaic acid reduced the Sp1 binding activity. Furthermore, okadaic acid treatment abrogated the lyso-PC induced promoter augmentation. Lyso-PC increased the nuclear extract protein phosphatase 2A (PP2A) activity, which was suppressed by okadaic acid treatment. These results suggest that lyso-PC up-regulates eNOS transcription by a PP2A-dependent increase in Sp1 binding activity.
Base Sequence↗
Systematic review of dietary intervention trials to lower blood total cholesterol in free-living subjects.
OBJECTIVES: To estimate the efficacy of dietary advice to lower blood total cholesterol concentration in free-living subjects and to investigate the efficacy of different dietary recommendations. DESIGN: Systematic overview of 19 randomised controlled trials including 28 comparisons. SUBJECTS: Free-living subjects. INTERVENTIONS: Individualised dietary advice to modify fat intake. MAIN OUTCOME MEASURE: Percentage difference in blood total cholesterol concentration between the intervention and control groups. RESULTS: The percentage reduction in blood total cholesterol attributable to dietary advice after at least six months of intervention was 5.3% (95% confidence interval 4.7% to 5.9%). Including both short and long duration studies, the effect was 8.5% at 3 months and 5.5% at 12 months. Diets equivalent to the step 2 diet of the American Heart Association were of similar efficacy to diets that aimed to lower total fat intake or to raise the polyunsaturated to saturated fatty acid ratio. These diets were moderately more effective than the step 1 diet of the American Heart Association (6.1% v 3.0% reduction in blood total cholesterol concentration; P<0.0001). On the basis of reported food intake, the targets for dietary change were seldom achieved. The observed reductions in blood total cholesterol concentrations in the individual trials were consistent with those predicted from dietary intake on the basis of the Keys equation. CONCLUSIONS: Individualised dietary advice for reducing cholesterol concentration is modestly effective in free-living subjects. More intensive diets achieve a greater reduction in serum cholesterol concentration. Failure to comply fully with dietary recommendations is the likely explanation for this limited efficacy.
Cholesterol↗
Homozygous deletion of the p16INK4A gene occurs more frequently in CD2+ than in CD2+ T-cell acute lymphoblastic leukemia.
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CD2 Antigens↗
Inhibitory effect of biphalin and AZT on murine Friend leukemia virus infection in vitro.
Biphalin is a bivalent opioid analogue containing two tyrosine residues. We have examined the effect of biphalin's anti-retroviral potency in vitro using a murine model. Biphalin, in non-cytotoxic concentrations, suppressed in a dose-dependent fashion the replication of Friend leukemia virus (FLV) in Mus dunni cells as determined using a focus forming assay. FLV replication was substantially reduced by biphalin at 10(-4) M concentration. When biphalin was combined with 3'-azido-3'-deoxythymidine (AZT) the two acted synergistically in inhibiting FLV replication compared to either used alone. Using a reverse transcriptase (RT) assay, FLV RT levels also were noted to be reduced in the presence of biphalin. These observations indicate that biphalin possesses anti-retroviral activity in vitro, suggesting that this opioid peptide should be examined further in vivo to determine if it is a candidate for combined therapy with AZT and possibly other drugs for retrovirus infections including the human immunodeficiency virus (HIV).
Antiviral Agents↗
High-dose therapy with peripheral blood stem cell (PBSC) support using an innovative mobilization regimen in patients with high-risk primary or chemoresponsive metastatic breast cancers.
High-dose therapy followed by peripheral blood stem cell (PBSC) support was performed in 29 patients with primary high-risk (Group I) or chemoresponsive metastatic (Group II) breast cancer patients. Group I patients had received PBSC mobilization within 4 weeks of modified radical mastectomy. Group II patients had to achieve minimal residual disease (MRD) by induction chemotherapy before being considered eligible for PBSC mobilization and high-dose therapy. An innovative FE120C regimen (5-FU 600 mg/m2, i.v., day 1; epirubicin 120 mg/m2, i.v., day 1; cyclophosphamide 600 mg/m2, i.v., day 1) plus G-CSF (300 microg/day, subcutaneous injection for 9 days, from day 4 post-FE120C) was used to mobilize PBSCs. After high-dose CTCb (cyclophosphamide 6,000 mg/m2, thiothepa 500 mg/m2, carboplatin 800 mg/m2, in 4 days), patients received PBSC infusion and daily C-CSF 300 microg subcutaneous injection. There were 19 and 16 patients enrolled into Group I and Group II, respectively. Ten of the Group II patients had achieved minimal residual disease (MRD) after induction chemotherapy. The median numbers of mobilized total CD34 + cells for Group I and Group II patients were 27.3 (9.2 to 114.1) x 10(6)/kg and 17.1 (5.9 to 69.1) x 10(6)/kg respectively. The median time to neutrophil recovery (ANC > or = 500/microL) was 8 and 9 days in Group I and II, respectively. The median time to platelet recovery (> or = 50,000/microL) was 10 and 15 days in Group I and II, respectively. No major treatment-related toxicities were noted. In Group I, 13 out of 19 patients (68.4%; 43-87%, 95% C.I.) remained recurrence-free with a median follow-up of 31 months (6 + to 55 + months). In Group II, 3 out of 10 patients (30%; 7-65%, 95% C.I.) remained progression-free at 33 +, 35 +, 39 + months from induction therapy. We suggest that the FE120C plus G-CSF is an effective and innovative regimen for PBSC mobilization in breast cancer patients, and high-dose CTCb therapy with PBSC support is a safe and well-tolerated treatment modality.
Adult↗
Acute and chronic arsenic poisoning associated with treatment of acute promyelocytic leukaemia.
Seven relapsed and/or refractory acute promyelocytic leukaemia patients were treated by arsenic trioxide (As2O3). Four patients (4/7, 57%) achieved complete remission after one to three cycles of treatment and the most common acute side-effect was fluid retention (in six patients, 86%), including weight gains and pleuro-pericardial effusions. Evident polyneuropathy compatible with chronic arsenic toxicity was noted in two of the three patients who received As2O3 maintenance therapy and one of them had marked distal muscular atrophy. We suggest that As2O3 may be a useful salvage therapy for relapsed and refractory APL patients, but the acute or chronic arsenic toxicity should be carefully monitored.
Acute Disease↗
Clonal disease of natural killer large granular lymphocytes in Taiwan.
Lymphoproliferative diseases of large granular lymphocytes (LDGL) may arise from either CD3+ T cells or CD3- natural killer (NK) cells. LDGL with clonal proliferation of large granular lymphocytes (LGL) is defined as LGL leukaemia. The number of patients with NK-LGL leukaemia reported is limited and the pathogenesis of the disease is not yet clear. From 1991 to 1998 six patients with cytogenetically proved clonal disease of NK-LGL were identified in our institute. All were seropositive for Epstein-Barr virus (EBV). EBV RNA or DNA could be detected in LGL from four patients by EBV in situ hybridization or Southern blot analysis. Most patients ran an aggressive clinical course and five died of the disease. Nonrandom clonal chromosomal abnormalities, including duplication of 1q, rearrangement at 3q and loss of chromosomes Y, 13 or 10, were noted in the six patients from this study and in eight from the literature. The implications of these recurrent cytogenetic aberrations in the development and progression of the disease deserve further studies.
Adolescent↗
The rpfA gene of Xanthomonas campestris pathovar campestris, which is involved in the regulation of pathogenicity factor production, encodes an aconitase.
Xanthomonas campestris pv campestris (Xcc) is a plant pathogenic bacterium that controls the production of pathogenicity factors in part by a cluster of genes designated rpf (regulation of pathogenicity factors). Sequence analysis of one of these genes (rpfA) revealed an open reading frame with amino acid sequence similarity to aconitases from other bacteria. Aconitase activity was lower in cellular extracts of an rpfA::Tn5 mutant than in those from the wild type. A zymogram of aconitase activity after native gel electrophoresis showed the presence of two distinct aconitases in Xcc; the major aconitase was absent in the rpfA::Tn5 mutant. This mutant also had reduced levels of extracellular enzymes and extracellular polysaccharide (EPS). Supplying rpfA in trans to the rpfA::Tn5 mutant restored both the major aconitase activity and the synthesis of these pathogenicity factors. The transcription of the genes for two extracellular enzymes (prtA, encoding a serine protease, and engXCA, encoding endoglucanase) was reduced in the rpfA mutant background. Because some eukaryotic aconitases are also involved in iron regulation, we explored a possible connection between rpfA and iron metabolism. Intracellular iron levels in the mutants were lower than in the wild type as assessed by sensitivity to the iron-activated antibiotic, streptonigrin. Wild-type bacteria grown in iron-deficient conditions had a similar sensitivity to streptonigrin as the aconitase mutant. Overall, these results suggest that a prokaryotic aconitase can also act as a regulator of gene expression and that the regulation is possibly related to changes in intracellular iron levels.
Aconitate Hydratase↗
The need to evaluate the clinical effectiveness of traditional Chinese medicine.
Traditional Chinese medicine is gaining increasing attention and popularity in Hong Kong. There is no doubt that traditional Chinese medicine as a system of medicine works; however, this does not imply that every therapy is efficacious. Prevention of the initiation and continuation of ineffective intervention is extremely important for the efficiency of any health care system. The evaluation of the clinical effectiveness of traditional Chinese medicine is thus a top priority. Efforts should be made to register all randomised trials in traditional Chinese medicine and to regularly review and disseminate the evidence from organised research. These actions are essential for the promotion and practice of evidence-based decision making in traditional Chinese medicine.
Journal Article↗
Familial transmission of human T-lymphotropic virus type 1 (HTLV-1) in patients with adult T-cell leukemia/lymphoma or HTLV-1-associated myelopathy.
The seroprevalence of human T-lymphotropic virus type 1 (HTLV-1) in Taiwan is 0.48%. In this study, we investigated the patterns of intrafamilial transmission of HTLV-1 in Taiwanese patients with adult T-cell leukemia/lymphoma (ATL/L) or tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). Fifteen index patients (9 men, 6 women, aged 31-71 yr), 13 with ATL/L, and two with TSP/HAM, and 98 relatives were included. Of the 98 relatives, 23 were seropositive for HTLV-1. Spouses of 11 patients were studied. Seven of eight wives of male patients but none of the three husbands of female patients were HTLV-1 carriers. Mother-to-child transmission was found in seven of 13 families and in 15 of 75 children tested. The correlation of breast-feeding with seropositivity in two families with seropositive mothers indicates its important role in vertical transmission of HTLV-1. Our findings suggest that husband-to-wife and mother-to-child transmission are the main forms of intrafamilial transmission of HTLV-1 in Taiwan, a nonendemic area. Screening for HTLV-1 in family members of patients with ATL/L or TSP/HAM, and seropositive blood donors, may be warranted. Seropositive individuals should be educated to prevent the spread of the virus through sexual contact and breast feeding.
Adult↗
Involvement of two Sp1 elements in basal endothelial prostaglandin H synthase-1 promoter activity.
Prostaglandin H synthase-1 (PGHS-1) is a constitutively expressed key enzyme in the biosynthesis of physiologically important prostanoids. The promoter of the human PGHS-1 gene lacks a TATA box, has a very GC-rich region, and contains multiple transcription start sites. To identify the elements involved in the constitutive expression of the PGHS-1 gene, we constructed a 2075-base pair fragment (-2095 to -21 relative to the translation start codon) and a series of 5'-deletion mutants into a promoterless luciferase expression vector, which was transfected in HUVEC. Two important regions were identified. DNase I footprinting identified a protected segment, which contains an Sp1 binding site proximal to the transcription start sites. Band shift assays confirmed specific binding of Sp1 to this segment. Band shift assays further revealed specific binding of Sp1 to a distal region containing a canonical Sp1 site. Mutation of either Sp1 binding site significantly reduced the promoter activity. When both sites were mutated, the activity was reduced to 29% of that of the wild type. Mutation of Sp1 sites did not abrogate promoter activity stimulated by phorbol ester. These results indicate that binding of Sp1 or its related proteins to two widely separated Sp1 sites on the promoter region activates the basal PGHS-1 gene transcription.
Base Sequence↗
Clinical and biological characteristics of acute promyelocytic leukemia in Taiwan: a high relapse rate in patients with high initial and peak white blood cell counts during all-trans retinoic acid treatment.
Acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA) and chemotherapy have been shown to have better outcome than those treated with conventional chemotherapy alone. However, the biological characteristics of leukemic cells and their clinical implications in patients treated with ATRA have not been well established. In this study, the biological and clinical features of 30 APL patients were reported. The risk factors for relapse and for occurrence of retinoic acid (RA) syndrome, which might cause morbidity or mortality of patients after ATRA treatment, were also analyzed. All patients showed 15;17 translocation by cytogenetic and/or gene analysis. Patients in this study had higher white blood cell (WBC) counts and a higher incidence of additional abnormalities than those from other areas. The ratio of long (L) form to short (S) form PML-RAR alpha fusion transcript was 1.8:1, a value lower than that of Latino patients but higher than that of Italians. Leukemic cells from four patients showed coexpression of T cell-associated antigen CD2 which was highly correlated with S form fusion transcript. Nine (36%) of the 25 patients treated with ATRA developed RA syndrome; all but one were successfully controlled by corticosteroid. Complete remission (CR) rate was 84%. Patients with high WBC counts tended to develop RA syndrome and had increased risk of relapse. Isochromosome for the long arm of the derivative chromosome 17, ider(17q), as an additional chromosomal abnormality was also associated with poor outcome in this study. In conclusion, APL in this study showed some different biological characteristics compared with those reported in other areas. High WBC count was a risk factor for relapse and development of RA syndrome after ATRA treatment. The prognostic implication of the presence of ider(17q) needs further clarification.
Adolescent↗
Clonal chromosomal abnormalities as direct evidence for clonality in nasal T/natural killer cell lymphomas.
Nasal T/natural killer (NK) cell lymphoma is a distinct clinicopathologic entity which is more prevalent in Asia than in America and Europe. The clonal nature of the infiltrating lymphoid cells is difficult to demonstrate because of the lack of immunologic markers for clonality and the absence of clonal T-cell receptor gene rearrangement in most cases. In this study, clonal chromosomal abnormalities were detected in the tumour cells from four patients with nasal T/NK cell lymphoma. This finding provided direct evidence for clonality of the disease. Moreover, nonrandom cytogenetic abnormalities, including isochromosome for the short arm (p) of chromosome 6, isochromosome for the long arm (q) of chromosome 1, partial deletion of 6q, and aberrations at 11q, were disclosed. Isochromosome 6p was the sole structural abnormality in one patient, which may be a pathognomonic change in nasal lymphoma.
Adult↗
Clinical, haematological and molecular studies in patients with chromosome translocation t(7;11): a study of four Chinese patients in Taiwan.
Translocation t(7;11)(p 15;p15) is an uncommon but recurrent chromosome aberration in acute myeloid leukaemia (AML). which occurs mostly in oriental patients and in AML M2 or, occasionally, M4 subtype. Recently, a consistent chimaeric fusion transcript NUP98-HOXA9 was found in several cases of t(7;11). Four AML cases with the chromosome abnormality in Taiwan are described. They were all adults with ages ranging from 30 to 41 years (median 36 years). Three of them were diagnosed as having AML M2; the remaining one as M4. Marked dyserythropoiesis was demonstrated in two patients. All four patients showed pan-myeloid antigen CD13 on the leukaemic cells, but none coexpressed lymphocyte-associated antigens and neither of the two patients studied for CD34 expression had positive staining. NUP98-HOXA9 fusion transcript was detected in both patients who had molecular analysis and the breakpoints on chromosome 11 and 7 respectively were similar to those previously reported. They all received conventional induction chemotherapy, but only one achieved a complete remission (CR) with short duration. This study and others reported in the literature suggest a racial or geographical predisposition among oriental patients to AML with t(7;11) and that this is associated with a poor prognosis. The molecular detection of NUP98-HOXA9 fusion transcript would be a useful method for the diagnosis of t(7;11) and also for monitoring disease status after treatment.
Adult↗
A novel regulatory system required for pathogenicity of Xanthomonas campestris is mediated by a small diffusible signal molecule.
Mutations in the seven clustered rpf genes cause downregulated synthesis of extracellular enzymes and reduced virulence of Xanthomonas campestris pathovar campestris (Xcc). The phenotype of mutants in one of the genes, rpfF, can be restored by a diffusible extracellular factor (DSF) produced by all Xcc strains tested, apart from rpfF and rpfB mutants. DSF accumulates in early stationary phase (when synthesis of enzymes is maximal), but levels decline subsequently. Addition of DSF to exponentially-growing wild-type bacteria does not cause precocious enzyme synthesis. rpfB and rpfF are expressed throughout growth, but the rate increases in early stationary phase. RpfB is predicted to be a long-chain fatty acyl CoA ligase, and RpfF shows some relatedness to enoyl CoA hydratases. The properties of DSF suggest that it may be a fatty-acid derivative, and certain lipid preparations possess DSF activity at higher concentrations. These include lipid extracts and acid-hydrolysed lipoplysaccharide and lipid A from Xcc, and purified dodecanoic and hydroxydodecanoic acid. DSF production is confined to certain xanthomonads. We propose a model for the DSF system, which represents a novel mechanism for regulating virulence factor synthesis in response to physiological or environmental changes.
Diffusion↗
Envelope gene sequences of human T-lymphotropic virus type 1 in Taiwan.
Three major types of HTLV-1 had been proposed, the Melanesian type, the Zairian type, and the cosmopolitan type, which was further divided into subtypes A, B and C, according to the phylogenetic tree constructed from LTR sequences of current HTLV-isolates. In this study, the envelope gene sequences of HTLV-1 from 9 Taiwanese were analyzed. Based on the phylogenetic tree constructed by unweighted pair group method and the sequence homology analysis by GCG computer programs, the envelope gene sequences of HTLV-1 proviruses from these 9 Taiwanese belonged to subtype A or subtype B of the cosmopolitan type and were closely related to HTLV-1 from Japan. Twelve subtype-specific nucleotide variations were deduced from the comparison of complete or partial envelope gene sequences of 16 HTLV-1 isolates of known subtypes as well as those of 9 Taiwanese. These data provided the basis for subtyping the cosmopolitan type of HTLV-1 by amplification of envelope gene sequences and restriction fragment length polymorphism studies. A more extensive survey based upon this proposal was warranted.
Base Sequence↗
Cloning and characterization of the rpfC gene of Xanthomonas oryzae pv. oryzae: involvement in exopolysaccharide production and virulence to rice.
rpfC is one of a cluster of genes which coordinately regulate the synthesis of extracellular enzymes and exopolysaccharide and pathogenicity in Xanthomonas campestris pv. campestris, the black rot pathogen of brassicas. An rpfC homolog which could functionally complement an rpfC mutant of X. campestris pv. campestris was identified in Xanthomonas oryzae pv. oryzae and the gene was characterized. Mutation of this gene in X. oryzae pv. oryzae had no effect on extracellular enzymes, but exopolysaccharide synthesis and virulence to rice were substantially reduced.
Bacterial Proteins↗