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Biomedical subjects

T H Lin

Publications and source records attributed to T H Lin.

At least 73 records · Page 4Linked to original sources

Additive effects of diltiazem and lisinopril in the treatment of elderly patients with mild-to-moderate hypertension.

A multicenter, double-blind, placebo-controlled trial with multifactorial design was conducted to evaluate the safety and efficacy of the calcium-channel blocker diltiazem, in a sustained release preparation, and the angiotensin converting enzyme inhibitor, lisinopril, in the treatment of elderly Chinese patients with mild-to-moderate hypertension. In addition to the hypotensive effects of combinations of both drugs compared with monotherapy, all given once daily, the effect on quality of life was also evaluated. This study consisted of a 3 x 2 multifactorial design in which 156 women and men with a sitting diastolic pressure of between 95 mm Hg and 114 mm Hg, after a 4-week placebo washout phase, were randomized to one of six treatment groups for 12 weeks of active treatment. Monotherapy with diltiazem 120 or 240 mg produced increasing reductions of systolic and diastolic blood pressure. Compared with placebo, lisinopril 10 mg had an effect intermediate between the diltiazem doses. The combinations of diltiazem 240 mg + lisinopril 10 mg and diltiazem 120 mg + lisinopril 10 mg showed increased efficacy in reducing systolic and diastolic blood pressure compared to these drug doses used in monotherapy, but the effect of the combinations was less than predicted by an additive model. Although the total number of other adverse events reported was similar for all active treatment groups compared to placebo, lisinopril-induced cough was common with an incidence of 31% after rechallenge. Premature drug withdrawal was necessary in four of 78 patients receiving lisinopril, due to intractable cough. The combination of diltiazem 240 mg and lisinopril 10 mg was significantly more effective at reducing blood pressure than either drug alone; this additive effect did not result in a higher rate of adverse effects or impairment of quality of life. Thus, combination therapy with these agents was well tolerated and resulted in increased efficacy in these elderly patients.

Aged↗

Spatio-temporal representation of multichannel EMG firing patterns and its clinical applications.

Analyzing motor unit (MU) activity is essential for studying the neurological dysfunction of upper motor neuron disorders (UMND). This study employs multichannel surface electromyographic (EMG) signals, as recorded from the upper arm during elbow flexion and extension, to analyze the temporal changes and spatial distribution of the dominant firing rate. To estimate the dominant firing rate, the autoregressive (AR) spectrum analysis method is utilized to detect the peaks and poles of the AR model, of the surface EMG spectrum below 40 Hz. The temporal changes in firing rates are also observed by using the spectrogram representation of low-frequency EMG spectra. The EMG spectrogram facilitates examination of the time-varying characteristics of firing rates and recruitment of MUs from surface EMG signal. The low-frequency spectra of multichannel EMG are then represented in a polar form to visualize the spatial distribution of firing patterns across muscles. Via spatio-temporal representation techniques, this study provides a viable approach of observing both the spatial and temporal patterns of MU activities in normal subjects and patients with UMND, including cerebrovascular disease and Parkinson's disease.

Cerebrovascular Disorders↗

The influence of psychological distress on use of genetic testing for cancer risk.

The recent identification of BRCA1, a breast cancer susceptibility gene, offers an unprecedented opportunity for high-risk individuals to learn whether they are genetically predisposed to develop breast or ovarian cancer. This study examined the relationships between psychological distress and use of BRCA1 testing by 149 high-risk individuals from hereditary cancer families. After a baseline assessment of demographics, objective risk, cancer-specific distress, and global distress (depressive symptoms), study participants were offered the opportunity to receive genetic counseling and to learn whether they carry a mutation in the BRCA1 gene. Overall, 58% of study participants requested BRCA1 test results, and 42% declined to learn their genetic status. After controlling for demographic factors and risk status, cancer-specific distress was significantly and positively related to BRCA1 test use, whereas global distress was unrelated to test use.

Adult↗

Incorporating biomarkers of exposure and genetic susceptibility into smoking cessation treatment: effects on smoking-related cognitions, emotions, and behavior change.

In this article the authors report on the short-term impact of incorporating biomarker feedback about exposure and genetic susceptibility into minimal-contact quit-smoking counseling (QSC). Four hundred and twenty-seven smokers were randomized to 1 of 3 treatments: (a) QSC, (b) QSC + exposure biomarker feedback (EBF) about carbon monoxide in exhaled breath, or (b) QSC + EBF + biomarker feedback about genetic susceptibility to lung cancer (SBF). We observed significant immediate positive effects of SBF, compared with EBF and QSC on perceived risk, perceived quitting benefits, and fear arousal. However, at the 2-month follow-up, there were no group differences in quit rates. SBF did lead to significant reductions in the number of cigarettes smoked for smokers who were in the preparation stage. Smokers in the EBF and QSC conditions showed reductions in depressive symptoms by 2 months, but smokers in the SBF condition did not. In the context of QSC, genetic feedback may heighten vulnerability and possibly promote distress, but may not immediately enhance quitting in most smokers.

Adolescent↗

The costs and effects of cervical and breast cancer screening in a public hospital emergency room. The Cancer Control Center of Harlem.

OBJECTIVES: This study assessed the cost-effectiveness of cervix and breast cancer screening in a public hospital emergency room. METHODS: Age-eligible women with nonurgent conditions and without recent screening were offered screening by a nurse. A decision analysis compared the costs and outcomes of emergency room screening and standard hospital screening efforts. RESULTS: The undiscounted cost-effectiveness results for establishing new programs were $4050 (cervical cancer), $403,203 (breast cancer), and $4375 (joint cervix and breast cancer) per year of life saved. If screening is added to an existing program, results are more favorable ($429, $21,324, and $479 per year of life saved for cervix, breast, and joint screening, respectively). Results were most sensitive to volume and probability of receiving treatment after an abnormal screen. CONCLUSIONS: Emergency room screening was cost-effective for cervical cancer; breast cancer screening was relatively expensive given the low number of women reached. More intensive recruitment and follow-up strategies are needed to maximize the cost-effectiveness of such programs.

Breast Neoplasms↗

[Primary surveillance of spotted fever group antibodies on rats in the Kinmen area].

The positive rate of rickettsial antibodies of 107 rats in the Kinmen area by indirect immunofluorescent antibody (IFA) technique was 0% (0/107) in typhus fever, 38.3% (41/107) in scrub typhus and 66.4% (71/107) in spotted fever group; the positive rate (42.9%) of spotted fever group of 21 rats in Taiwan island also higher than scrub typhus (19.0). It suggests that spotted fever group patients may be present in our country but have not been discovered.

Animals↗

Nonenzymatic isomerization of 9-cis-retinoic acid catalyzed by sulfhydryl compounds.

Certain thiol-containing compounds catalyze, in a chemical reaction, the isomerization of 9-cis-retinoic acid to a mixture of all-trans-retinoic acid, 9-cis-retinoic acid, 13-cis-retinoic acid, and 9,13-dicis-retinoic acid. In the presence of such catalysts, all-trans-retinoic acid gives rise to the same mixture. Reactions approaching equilibrium contain more all-trans-retinoic acid than either of the other isomers. Small molecules effective as catalysts are mercaptoethanol, L-cysteine methyl ester, glutathione, and N-acetyl-L-cysteine. Apoferritin (a thiol-containing protein), native microsomes, and, to a lesser extent, boiled microsomes catalyze the reaction. In intact cells, these interconversions also occur in a process inhibited by a sulfhydryl-specific reagent. The thiol-catalyzed isomerization of 9-cis-retinoic acid may be relevant in the biological activity of this compound.

Alitretinoin↗

Spontaneous remission in acute myelogenous leukemia: a case report.

A 62-year-old woman with hypocellular acute myelogenous leukemia experienced spontaneous remission after repeated episodes of severe infections. Transient surge of profuse blasts in the peripheral blood was observed prior to the occurrence of spontaneous remission. The duration of the spontaneous remission was relatively short, and the disease relapsed five months later. A second complete remission was achieved after chemotherapy with low-dose cytosine arabinoside. The patient finally died of relapsed leukemia after a second remission of three year duration. Possible mechanisms implicated in the occurrence of spontaneous remission in this patient are discussed.

Antimetabolites, Antineoplastic↗

The genome of Moloney murine leukemia virus can be integrated by the integrase of human immunodeficiency virus type 1 expressed alone in vivo.

An in vivo integration assay using the expressed human immunodeficiency virus type 1 (HIV-1) integrase (IN) protein and plasmids carrying a copy of the infectious Moloney murine leukemia virus (MuLV) provirus genome as substrates is presented. The HIV-1 IN gene was taken from vector pINSD and cloned into vector pXT1 to give pXT1-IN. Two and three nucleotides from the circle junction on one pair of U3 and U5 attachment (att) sequences on an infectious MuLV provirus vector pMLV-K were changed by means of site-directed mutagenesis to that of the corresponding HIV-1 att sequences to generate vector pMLV*(U3U5). The MuLV IN sequence was partially deleted for vectors pMLV-K and pMLV*(U3U5) to generate vectors pMLV delta IN and pMLV*(U3U5) delta IN. Integration of these wild type and MuLV IN partially deleted or att mutated MuLV provirus vectors in the transfected cells by the expressed HIV-1 IN was monitored by means of a non-radioactive reverse transcriptase (RT) assay for released and collected virions. No RT activity was detected for the NIH/3T3 cell singly transfected with vector pMLV delta IN. However some RT activities were observed for the HIV-1 IN expressing cell transfected either with vectors pMLV delta IN or pMLV*(U3U5) delta IN. This indicated that in the absence of other HIV-1 proteins expressed the MuLV provirus genome was integrated by the expressed HIV-1 IN protein. The integration of these MuLV provirus genomes was further confirmed by polymerase chain reaction analysis on the genomic DNA extracted from the transfected cells using the MuLV IN sequence remained from partial deletion as a target.

Cell Line↗

Pyogenic myositis: caused by viridans streptococci in an adult with tetralogy of Fallot.

A 34-year-old man came to this Emergency Room because of fever, swelling and pain in the right thigh. Tetralogy of Fallot with bicuspid pulmonary valve was diagnosed after serial examination, and computed tomography of the right thigh revealed pyogenic myositis. Surgical drainage of the right thigh abscess and a further pus culture yielded viridans streptococci. There has been no record in the medical literature of a pyogenic myositis caused by viridans streptococci in an adult tetralogy of Fallot. This is thus the first case reported.

Adult↗

Malignant lymphomas of sinonasal region, including cases of polymorphic reticulosis: a retrospective clinicopathologic analysis of 34 cases.

BACKGROUND: Lymphomas occurring in nasal cavities and paranasal sinuses are uncommon neoplasms in Western, but are reported to be higher in Oriental, countries. A retrospective study was performed to analyze the clinical and pathological characteristics of sinonasal lymphomas/polymorphic reticulosis at Taichung Veterans General Hospital during a 14-year period. METHODS: At Taichung Veterans General Hospital, 37 patients with sinonasal lymphomas (including three patients with polymorphic reticulosis) were seen from November 1982 through September 1996. Excluding three patients without sufficient data, a total of 34 patients with their clinical records were reviewed. Clinical information regarding characteristics of the tumors, histological studies, treatment modalities and follow-up was collected for analysis. RESULTS: The 34 patients who underwent review showed a male-to-female ratio of 2.1:1. Median age was 60 years (range 13-83 years). The most common symptoms were nasal obstruction, nasal discharge/rhinorrhea and epistaxis. Median duration of symptoms at the time of diagnosis was two months. The most frequently involved sites were nasal cavities (right more than left side). There were 31 non-Hodgkin's lymphomas and three polymorphic reticuloses. The pathological classifications revealed 13 diffuse large cell lymphomas, 14 diffuse mixed small and large cell lymphomas and four pleomorphic T-cell lymphomas. Of the 21 adequately staged patients, 13 patients were in stage I; four, stage II; two, stage III and two, stage IV. The immunophenotypic study was performed in 20 patients. Eighteen (90%) of them were T-cell lymphomas and only two cases (10%) derived from B-cell. Though approach to therapy and follow-up periods varied during the time period covered by this study, the differences in survival according to treatment modalities were not statistically significant. The follow-up period ranged from 9 days to 130 months. The mean survival was 84.2 months. The overall five-year survival rate was 63%. CONCLUSIONS: The majority of the cases here were T-cell lymphomas. Most histologic grading by Working formulation belonged to the intermediate grade. Optimal treatment for such a group of patients still has no consensus, but adequate local control is important. If diagnosed and treated early, primary sinonasal lymphomas can be associated with a favorable outcome even with local treatment alone.

Adolescent↗

Evidence for arylamine N-acetyltransferase in the nematode Anisakis simplex.

N-Acetyltransferase activities with p-aminobenzoic acid and 2-aminofluorene were determined in Anisakis simplex, a nematode found in the intestine of the salt water fish Trichiurus lepturus. The N-acetyltransferase activity was determined using an acetyl CoA recycling assay and high pressure liquid chromatography. The N-acetyltransferase activity from a number of Anisakis simplex whole tissue homogenizations was found to be 2.89 +/- 0.52 nmol/min per mg for 2-aminofluorene and 2.54 +/- 0.45 nmol/min per mg for p-aminobenzoic acid. The K(m) and Vmax values obtained were 1.06 +/- 0.69 mM and 9.34 +/- 1.94 nmol/min per mg for 2-aminofluorene, and 2.25 +/- 0.10 mM and 14.44 +/- 0.7 nmol/min per mg for p-aminobenzoic acid. The optimal pH value for the enzyme activity was pH 8.0 for both substrates tested. The optimal temperature for enzyme activity was 37 degrees C for both substrates. The N-acetyltransferase activity was inhibited by iodoacetamide: at 0.25 mM iodoacetamide, activity was reduced 50% and 1.0 mM iodoacetamide inhibits activity more than 90%. Among a series of divalent cations and salts, Cu2+ and Zn2+ were demonstrated to be the most potent inhibitors. This is the first demonstration of acetyl CoA/arylamine N-acetyltransferase activity in a nematode and extends the number of phyla in which this activity has been found.

4-Aminobenzoic Acid↗

Integrin-mediated activation of MEK and mitogen-activated protein kinase is independent of Ras [corrected].

The integrins are a family of cell surface receptors that mediate adhesive interactions with the extracellular matrix and also generate signals that influence cell growth and differentiation. Ligation and clustering of integrins causes activation and autophosphorylation of focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase, and results in the transient activation of p42 and p44 mitogen-activated protein (MAP) kinases. Initial evidence has suggested that the integrin signaling pathway may share common elements with the canonical Ras signal transduction cascade activated by peptide mitogens such as epidermal growth factor (EGF). In this report we demonstrate that Raf-1 and MAP or extracellular signal-related kinase kinase (MEK), key cytoplasmic kinases of the Ras cascade, are activated subsequent to integrin-mediated adhesion of mouse NIH 3T3 fibroblasts. We also show that MAP kinase is downstream of MEK in the integrin signaling pathway. However, in contrast to the receptor tyrosine kinase signaling cascade, integrin-mediated signal transduction seems to be largely independent of Ras. Dominant negative inhibitors of Ras-dependent signaling failed to block integrin-mediated activation of MEK. In addition, while treatment with the peptide mitogen EGF clearly increased GTP-loading of Ras, little effect was observed in response to integrin-dependent cell adhesion. Thus, integrin-mediated activation of MEK and MAP kinase in 3T3 cells occurs primarily by a mechanism that is distinct from the Ras signal transduction cascade.

3T3 Cells↗

Participation in a women's breast cancer risk counseling trial. Who participates? Who declines? High Risk Breast Cancer Consortium.

BACKGROUND: Little is known about what factors influence women to participate its trials designed for women at high risk for breast cancer. Yet the recruitment phase is of utmost importance in determining whether the trial can achieve its goals. The purpose of this study was to examine predictors of participation in a risk counseling trial for first-degree relatives of breast cancer patients. METHODS: Subjects were identified by their relatives who had received a diagnosis of breast cancer at one of six institutions. Letters of introduction were sent to potentially eligible, unaffected relatives. They were informed about the risk counseling study and given the opportunity to decline. Letters were sent to 1392 first-degree relatives; of these, 1149 women were contacted for an interview and 14% refused. Of the 987 respondents, 47% accepted and 53% declined to participate. Bivariate and multivariate statistics were used to examine predictors of participation. RESULTS: In the total sample, there were five significant multivariable predictors of participation: level of education, recent clinical breast examination (CBE), objective and perceived breast cancer risk, and any current use of alcohol. Participation was moderated by time since the relative's diagnosis. There was a statistically significant relationship to education such that women with a higher level of education were significantly more likely to participate if they were approached within 2 months of their relative's diagnosis of breast cancer. CONCLUSIONS: Like many other kinds of trials, participants in this risk counseling trial were significantly more likely to have more than a high school education and more likely to be nonsmokers than the nonparticipants. They also were significantly more likely to drink alcohol (dichotomous measure), have had a recent CBE, and have higher subjective and objective breast cancer risks. Different types of recruitment strategies may be needed depending on the characteristics of the people being recruited and the timing of the invitation.

Adult↗

Concordance between rats and mice in bioassays for carcinogenesis.

According to current policy, chemicals are evaluated for possible cancer risk to humans at low dose by testing in bioassays in which high doses of the chemical are given to rodents. Thus, risk is extrapolated from high dose in rodents to low dose in humans. The accuracy of these extrapolations is generally unverifiable because data on humans are limited. However, it is feasible to examine the accuracy of extrapolations from mice to rats. If mice and rats are similar with respect to carcinogenesis, this provides some evidence in favor of interspecies extrapolations; conversely, if mice and rats are different, this casts doubt on the validity of extrapolations from mice to humans. One measure of interspecies agreement is concordance, the percentage of chemicals that are classified the same way as to carcinogenicity in mice and rats. Observed concordance in National Cancer Institute/National Toxicology Program bioassays is about 75%, which may seem on the low side because mice and rats are closely related species tested under the same experimental conditions. However, observed concordance could underestimate true concordance due to measurement error in the bioassays-a possibility demonstrated by Piegorsch et al. (Risk Anal. 12, 115-121, 1992). Expanding on this work, we show that the bias in observed concordance can be either positive or negative: an observed concordance of 75% can arise if the true concordance is anything between 20 and 100%. In particular, observed concordance can seriously overestimate true concordance.

Animals↗

Murine toxicology and pharmacology of UAB-8, a conformationally constrained analog of retinoic acid.

(2E, 4E, 6E)-8-[3'-Ethyl-2'-(1-methylethyl)-2'-cyclohexen-1'-ylidene] -3, 7-dimethyl-2,4,6-octatrienoic acid (UAB-8) has potent activity in preventing papillomas on the skin of mice similar to that determined in a previous study for the homolog containing one less carbon atom. To evaluate the toxicological profile for UAB-8, relative to all-trans-retinoic acid (RA), female mice were dosed by oral gavage for 29 days with amounts of 0.05, 0.1, or 0.2 mmol/kg/day. For the two compounds, the effects on body weights were similar. Mice dosed with UAB-8, however, had a lower incidence of clinical signs of toxicity (alopecia, scaly skin, and limping). At necropsy, bone fractures, skin abnormalities, and splenomegaly were observed in some mice dosed with RA but not in any dosed with UAB-8. Lymph node hyperplasia was noted in some mice dosed with either dose of RA but only in those dosed with the highest dose of UAB-8. All dose levels of RA produced microscopic lesions in the bones of mice; only the highest dose of UAB-8 had this effect. RA and UAB-8 had similar effects on chondrogenesis in cultures of cells from mouse limb buds, an indication of comparable teratogenic effects. For mice dosed i.v. (10 mg/kg), there was a saturated phase of elimination of RA from plasma (Km = 0.61 microgram/ml and Vmax = 2572 micrograms/hr); no such phase was noted when UAB-8 was administered. UAB-8 had values for t1/2 alpha and t1/2 beta of 0.47 and 17.1 hr, respectively. Relative to RA, UAB-8 has a favorable toxicological profile and different pharmacokinetics.

Animals↗

Determination of zinc fractions in human blood and seminal plasma by ultrafiltration and atomic absorption spectrophotometry.

A simple and reliable method is described which combines ultrafiltration technique with atomic absorption spectrophotometry to determine the Zn fractions in human blood plasma and seminal plasma. Ultrafiltrable, loosely bound, and firmly bound Zn can be measured using this method in the presence or absence of ethylenediaminetetraacetic acid (EDTA). The YMT membranes for the ultrafiltration must be rinsed thoroughly before use. In contrast to Zn in blood plasma, a large part of Zn in the seminal plasma was found to be ultrafiltrable. This method can be applied to study the physiologically active part of Zn in body fluids related to various disease states.

Adult↗

Trace elements and lipid peroxidation in uremic patients on hemodialysis.

Trace elements and lipid peroxidation in 26 patients with chronic renal failure treated with hemodialysis and 25 healthy subjects were observed. Both plasma and erythrocyte trace elements and plasma malon dialdehyde (MDA) were examined immediately before and after hemodialysis. Increased levels of plasma Cu, MDA, and erythrocyte Pb, Mn, Zn, and a significantly decreased plasma Se, Zn, and erythrocyte Se were found in patients before hemodialysis. After a single hemodialysis, erythrocyte Mn, Cu, Zn, and plasma Cu, Al, and MDA were significantly increased whereas both plasma and erythrocyte Se were lower in patients than in healthy subjects. The level of MDA was not significantly changed during the single hemodialysis. Both plasma and erythrocyte Zn levels and plasma Cu and Al were significantly higher after hemodialysis than before hemodialysis. In conclusion, levels of trace elements are altered by hemodialysis, which may increase patient susceptibility to lipid peroxidation in uremia.

Adult↗