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Biomedical subjects

T C Hsu

Publications and source records attributed to T C Hsu.

At least 91 records · Page 5Linked to original sources

Lung cancer, smoking patterns, and mutagen sensitivity in Mexican-Americans.

BACKGROUND: Mexican-Americans have lower age-adjusted lung cancer incidence rates than non-Hispanic whites and African-Americans. Since 87% of lung cancers are attributed to tobacco exposure, this difference could be explained partly by lower prevalence of cigarette smoking. However, only a fraction of exposed individuals will develop smoking-related cancer, and genetically determined differences in modulation of environmental exposures could also explain some of this ethnic risk differential in lung cancer incidence in the United States. However, little research on genetic susceptibility has been focused on Hispanic populations in the United States. METHODS: We are conducting a case-control study of lung cancer in a high-risk group (African-Americans) and a low-risk group (Mexican-Americans) to evaluate ethnic differences in mutagen sensitivity by an in vitro assay that quantifies mutagen-induced chromosome breaks in short-term lymphocyte cultures. RESULTS: In the 174 Mexican-Americans (67 lung cancer case patients and 107 control subjects) accrued to date, all measures of cigarette smoking (intensity, duration, nicotine and tar contents, depth of inhalation, and type of cigarette) were significant predictors of lung cancer risk. There were significantly higher risks associated with mutagen sensitivity (defined as > or = 1 break/cell) for both former smokers (odds ratio [OR] = 4.5; 95% confidence interval [CI] = 0.9-21.9) and current smokers (OR = 2.6; 95% CI = 0.6-11.1). Mutagen sensitivity also appeared to be implicated in risk in patients who were less than 55 years old at diagnosis (OR = 15.0; 95% CI = 1.0-228.9) and in those with lower cigarette exposure (OR = 11.0; compared with an OR of 1.7 for the heaviest smokers). The overall OR for mutagen sensitivity adjusted for age, sex, and pack-years of smoking was 2.9 (95% CI = 0.8-9.9). Neither current smoking status nor years of exposure shifted the sensitivity profile of case patients and control subjects. CONCLUSION: Although this study showed higher percentages of nonsmokers among Mexican-Americans than our previously reported data for African-Americans, the Mexican-American case patients were heavier smokers than the African-American case patients. The prevalence of mutagen sensitivity for Mexican-Americans was 64.1% in case patients and 26.2% in control subjects. In African-Americans, mutagen sensitivity was previously reported to be 55.3% in case patients and 24.6% in control subjects. These preliminary data do not support our a priori hypothesis that a lower prevalence of mutagen sensitivity in Mexican-Americans would account for the lower incidence of lung cancer. Mutagen sensitivity, however, is only one of an array of potential susceptibility markers that we are evaluating in this unique population.

Black or African American↗

Mutagen sensitivity as a risk factor for second malignant tumors following malignancies of the upper aerodigestive tract.

BACKGROUND: Second malignant tumors in patients successfully treated for an initial cancer of the upper aerodigestive tract are an important cause of morbidity and mortality. Biologic markers capable of identifying high-risk subgroups of patients who could be targeted for intensive clinical surveillance, therefore, have immense therapeutic and prognostic relevance. We previously demonstrated in a pilot study of 84 patients with cancers of the upper aerodigestive tract that mutagen sensitivity was a significant predictor of risk of developing second malignant tumors. PURPOSE: We extended the study to include 278 patients diagnosed with previously untreated cancers of the upper aerodigestive tract from 1987 to August 1993. METHODS: For each patient, base-line (pretreatment) mutagen sensitivity was measured in vitro in 50 metaphases established from peripheral lymphocyte cultures. Patients with an average of more than 1 chromosomal break/cell were deemed mutagen hypersensitive. Cox proportional hazards analysis was used to predict the risk of developing second malignant tumors associated with mutagen sensitivity. RESULTS: Overall, 44% of the case group exhibited mutagen hypersensitivity. There were no differences in the distribution of mutagen hypersensitivity by site, sex, stage of disease, or smoking status. There were 17 synchronous and 11 metachronous cancers, of which 15 (54%) were smoking-related malignancies. Sixteen (13.1%) of the mutagen-sensitive patients developed second malignant tumors, compared with 12 (7.7%) of the nonsensitive patients. The mean break/cell value (+/- SD) for patients developing second malignant tumors was 1.17 (+/- 0.54), compared with 0.98 (+/- 0.44) for patients with only one cancer (P = .04). Mutagen hypersensitivity conferred a relative risk of 2.67 (95% confidence interval = 1.22-5.79) of developing second malignant tumors. CONCLUSIONS: Mutagen hypersensitivity increases the risk of developing second malignant tumors. IMPLICATIONS: Future research should focus on the molecular mechanisms underlying mutagen sensitivity.

Adult↗

Performance on a dementia screening test in relation to demographic variables. Study of 5297 community residents in Taiwan.

OBJECTIVE: To examine the relation between performance on a dementia screening test and the demographic variables of age, education, gender, and urban vs rural residency. DESIGN: Community survey with cluster sampling. SETTING: One urban and one rural community from each of four geographic regions in Taiwan, Republic of China. PARTICIPANTS: A total of 5265 nondemented individuals approximately equally divided between men and women and between urban and rural residency with a range in age from 41 to 88 years and in education from 0 to 20 years. MAIN OUTCOME MEASURE: Score on a Chinese adaptation of the Mini-Mental State Examination. RESULTS: Lower test scores were associated with older age and less education. The decrease in score with age was faster among participants who had never attended school. Better performance by men and by urban residents was found only among participants with fewer than 6 years of schooling. In this group, the magnitudes of sex and residency differences were comparable among those subjects aged 41 to 64 years and those aged 65 to 88 years. Women who had never worked outside of the home performed poorer than those who had worked outside of the home. CONCLUSIONS: The influence of educational background on test performance is most evident in individuals with less education. Commonly used dementia screening tests may be unfair to poorly educated individuals, especially women and rural residents. Efforts should be made to develop ecologically relevant cognitive tests for the intended study populations. To help distinguish test bias from different rates of cognitive decline, the study populations should include individuals in predementia age ranges.

Adult↗

Fitting a two-parameter logistic item response model to clarify the psychometric properties of the Drug Use Screening Inventory for adolescent alcohol and drug abusers.

The suitability of fitting a two-parameter logistic item response model to the Drug Use Screening Inventory (DUSI) was assessed. In a sample of 846 adolescents, each of the 10 domains was found to be unidimensional. Invariance of the item parameters across different groups was also observed. The reliability coefficient, based on item response theory, was found to be superior. The results of these analyses indicate that the DUSI has sound psychometric properties.

Adolescent↗

Mutagen sensitivity as a marker of cancer risk.

There are measurable differences, genetically determined, in susceptibility to carcinogenic activity. Variation in metabolism of xenobiotic chemicals is one determinant of susceptibility and is attributed to polymorphisms in a number of enzymes. There may also be a wide spectrum of DNA-repair capability within the population. A peripheral lymphocyte assay has been developed in which in vitro bleomycin-induced chromosome breaks provides an indirect measurement of such repair. Mutagen sensitivity as defined by this assay has been shown to be an independent risk factor for tobacco-related malignancies, especially those of the upper aerodigestive tract. Preliminary data also suggest familial aggregation of cancer in mutagen-sensitive patients. Risk assessment is now recognized as a multidisciplinary process, extending beyond the scope of traditional epidemiologic methodology to include biological evaluation of interindividual differences in carcinogenic susceptibility. These susceptibility markers will enable us to identify high-risk population subgroups that can be targeted for intensive primary and secondary preventive strategies.

Anticarcinogenic Agents↗

[Clinical application of the ice water test in evaluation of neurogenic bladder dysfunction].

Ice water test (IWT) and cystometrography (CMG) were performed on 51 in patients with spinal cord injuries (SCI) to evaluate the sensitivity and specificity of the IWT in detecting detrusor reflex. A three-step grading system as established by Balmaseda et al was applied to determine the presence of detrusor activity on IWT. The test was considered 3+ when the catheter was expelled from the bladder within one minute following instillation of 90 mL of ice water; a 2+ test indicated voiding around the catheter after instillation of 90 mL of ice water; and a 1+ IWT was defined as voiding around the catheter or expelling the catheter after instilling another 210 mL of ice water into the bladder. The results showed that the sensitivity of IWT in detecting the presence of detrusor reflex in patients with neurogenic bladder dysfunction was 96% and the specificity was 79%. Among the four patients having false positive IWT, three of them were diagnosed with poor-compliance bladders. One patient with false negative IWT was found to have severe detrusor-sphincter dyssynergy. There was a significant difference in the strength of detrusor activity among the patients with 3+ IWT, with 2+ IWT, and with 1+ IWT. IWT is a useful technique to predict the existence of detrusor reflex in SCI patients. Its use as a supplement method to cystometrogram could be helpful in the bedside evaluation of patients with neurogenic bladder dysfunction.

Adult↗

Stress fractures of the ribs in amateur golf players.

BACKGROUND: Stress fractures of the ribs are sometimes seen at the Outpatient Department in patients with a history of playing golf enthusiastically. Many are diagnosed as "muscle strain" or "myofascial pain" and patients are simply advised to take some rest or are treated with analgesics and local injection. This case study investigated 11 amateur golfers whose chief complaint was anterior, posterior or lateral chest pain. After X-ray and bone scan evaluation, "stress fracture of the ribs" was diagnosed. A questionnaire presented to them trying to find the possible mechanisms of these stress fractures. Biomechanical analysis showed that the bending force of the ribs was located at posterolateral segments where fractures tend to occur. Overuse, poor technique and inadequate stretch in beginners are postulated as causes for apparent increased susceptibility to these skeletal injuries. METHODS: Questionnaires inquired about (1) warm-up time, (2) number of strikes, (3) fracture sites, (4) pain patterns, (5) combined injuries. RESULTS: All 11 patients were beginners with right side hand dominance who had begun to play golf within the year. Right side ribs fracture occurred in six cases; left side ribs fracture occurred in eight cases including three patients with two fracture sites. Localized pain was reported in six cases and there were five cases with radiating pain along costal margins. All the golfers had spent no more than 10 minutes in warm up them. Seven patients suffered from multiple injuries after they had played. Five were diagnosed by X-ray and six showed positive finding after Tc-99m MDP bone scan. All lesions were located at the posterolateral segments of the ribs. CONCLUSIONS: Stress fractures of the ribs in amateur golfers are certainly not uncommon. Predominant muscle forces are generated by forced coupling of scapular retraction and protraction, acting through the serratus anterior. With early diagnosis and relative rest for four to eight weeks, the pain will improve. Overuse, poor technique and inadequate stretch will probably lead to stress fracture of the rib.

Biomechanical Phenomena↗

Inflammatory fibroid polyp of the jejunum causing intussusception: a case report.

Inflammatory fibroid polyp is a rare benign lesion of the gastrointestinal tract. This report concerns a 56-year-old female who presented with intermittent abdominal pain, vomiting and diarrhea; she had had partial intestinal obstruction over a period of two months. Plain abdomen showed dilatation of the small bowels. Abdominal echo revealed intussusception of the small intestine. During exploratory laparotomy a polypoid dumb-bell shaped polyp was noted as the leading point of the jejunojejunal intussusception, segmental resection of the jejunum was performed. Histological features of the polyp met the diagnosis of inflammatory fibroid polyp.

Female↗

Assembly of glucocorticoid receptor and c-JUN homodimer on the promoter of mouse mammary tumor virus-long terminal repeat is influenced by order of addition.

Interactions between the glucocorticoid receptor (GR) and c-Jun/c-Jun homodimer (JUN) on the promoter DNA of mouse mammary tumor virus-long terminal repeat (MMTV-LTR) are reported here using the electrophoretic mobility shift assay (EMSA). Both GR and JUN are capable of independently binding to their respective response elements, including glucocorticoid response element (GRE) and phorbol ester response element (TRE), on MMTV-LTR promoter. The protein-DNA complex, assembled by pre-incubating JUN and DNA before the addition of GR, migrates slower (supershift) on gel electrophoresis than do the complexes formed by the other orders of addition. The formation of the supershifted complex is GR and JUN dose-dependent. The supershift is not detected with the cleaved fragments of MMTV-LTR promoter that separate GRE from TRE, indicating that the integrity of the promoter and possibly the spacing between GRE and TRE are important. The interaction of GR and JUN on the MMTV-LTR promoter appears to be more complex than simple protein-protein interaction.

Adrenalectomy↗

The genetics of tobacco-induced malignancy.

OBJECTIVE: Several areas of investigation contribute to an increasing understanding of the genetics of malignancies associated with tobacco use. While the strong influence of tobacco exposure on cancer development obscures genetic influences, there are indications that aspects of cancer susceptibility may have a heritable basis. In addition, specific sites within the genome appear to be commonly involved in these malignancies. This review describes research relevant to investigation of the genetics of tobacco-induced malignancy. DATA SOURCES: A review of the pertinent literature covered the past 20 years. References were gleaned from a variety of sources including manual review of the most recent journals, a computerized database (Mini-MEDLINE), references cited in previous works, and our own ongoing research in cancer genetics and molecular biology. STUDY SELECTION AND DATA EXTRACTION: Whenever possible, controlled studies from peer-reviewed journals were used. Where studies have shown conflicting results, the possible confounding factors are discussed. DATA SYNTHESIS: From a broad array of research areas, a view of the genetic aspects of tobacco carcinogenesis emerges. This includes syndromic and nonsyndromic susceptibility, genetic determinants of carcinogen metabolism, DNA adduct formation, and site-specific genetic alterations in tobacco-induced malignancy. In addition to specific gene alterations commonly seen in tobacco-induced malignancy, viral infections may contribute to cancer development through pathways related to tobacco carcinogenesis. CONCLUSION: Further research on many aspects of tobacco-induced carcinogenesis is warranted. Investigation of cancer susceptibility may contribute to understanding DNA surveillance and repair pathways. Carcinogen metabolism investigations have application in cancer detection and prevention schemes. Further understanding of tumor suppressor gene function and the role of gene amplification in carcinogenesis may allow design of gene-specific strategies in cancer treatment.

Carcinogens↗

In vitro protective effects of chemopreventive agents against bleomycin-induced genotoxicity in lymphoblastoid cell lines and peripheral blood lymphocytes of head and neck cancer patients.

The protective effects of ascorbic acid (AA), n-acetyl-l-cysteine (NAC), alpha-tocopherol acid (ATA), alpha-tocopherol-acid succinate (TAS), and 13-cis-retinoic acid (CRA) on mutagen-induced chromosomal breakage were studied. Mutagen-sensitivity was determined by the bleomycin assay in human lymphoblastoid cell lines (LCLs) and cultures of peripheral blood lymphocytes (PBLs) from head and neck cancer patients. Preincubation with chemopreventive agents statistically significantly decreased mutagen-induced chromatid breakage in LCLs and PBLs in a dose-related manner. As the concentration of the agents was increased in tenfold increments in the study range, mean breakage rates were reduced by 3.0 to 7.7% in LCLs and by 6.0 to 11.1% in PBLs. The effective concentrations are comparable to those achieved in clinical applications and found in human dietary studies. A similar phenomenon in vivo, if identified, may explain the differences in occurrence of head and neck and other cancers between populations with different dietary habits. The bleomycin assay may be used for studying compounds with presumed chemopreventive properties.

Acetylcysteine↗

[The effect of surface area of active recording electrode to CMAP parameters].

The purpose of this study is to quantitatively evaluate the effect of surface area of active recording electrodes to CMAP. The APB muscles from 19 young healthy subjects were included. The evoked CMAPs from median nerve supramaximal stimulation at wrist were recorded with regular surface disc electrode. Then the active recording electrode were changed to 1/2 surface area of disc, 1/4 surface area of disc, monopolar needle and concentric needle at the same recording sites. Computer reading of the latency, duration, amplitude and surface area of the CMAP were done and compared to that of standard electrode. Results disclosed that decrease the surface area of active recording did not significantly influence the distal latency, duration, amplitude and surface area of the CMAP (p > 0.1), although tendency to increase the amplitude and area were noted. The recording abilities of the active recording and the surface area difference between active recording and reference were considered to be the contributing factors. In clinical application such as recording an area with skin defect, the surface area of active recordling electrode can be altered without significant distortion of CMAP parameters.

Action Potentials↗

Novel nucleolar and nuclear morphology in a vincristine-dependent human leukemia cell line (L100).

Acquired resistance to chemotherapeutic drugs by tumor cells is an important obstacle to effective therapy of human malignancy. We now describe a vincristine (VCR)-induced multidrug-resistant (MDR) human acute lymphatic leukemia cell line, the sustained in vitro growth of which is dependent on vincristine. The doubling time for parental drug-sensitive cells (L0) is 40.2 +/- 13.2 h and for the MDR subline (L100) 62.5 +/- 11.3 h. L100 cells have similar G2 and mitotic phase to parental cells, express the MDR phenotype, and are characterized by novel morphologic features with multilobulated nuclei and multiple small nucleoli. Compared with L0 cells which have 2-3 nucleoli per cell, L100 cells have 7-8 nucleoli per cell. Average nucleolar area is 11.3 +/- 7.3 microns 2 for L0 and 2.5 +/- 2.4 microns 2 for L100 cells determined by the laser scanning method. The striking morphologic abnormalities of L100 cells suggest a drug-induced cytoskeletal abnormality. The relationship of these abnormalities to the VCR growth dependence of L100 cells is discussed.

Cell Cycle↗

Anticlastogenic effects of 13-cis-retinoic acid in vitro.

The anticlastogenic effects of 13-cis-retinoic acid were studied in four human lymphoblastoid cell lines and in primary lymphocyte cultures derived from the peripheral blood of 11 study subjects. Cells were pre-incubated with 13-cis-retinoic acid in the concentration range of 10(-8)-10(-5) mol/l for 24 h and the numbers of chromatid breaks per cell induced by bleomycin were determined. The presence of 13-cis-retinoic acid decreased the number of breaks per cell by 13.0 to 59.5% in lymphoblastoid cell lines and by 0 to 57.4% in primary lymphocyte cultures (in the concentration ranges of 10(-8)-10(-6) mol/l and of 10(-8)-10(-5) mol/l, respectively). Regression analysis showed that there was a statistically significant correlation between the presence of 13-cis-retinoic acid and protection against bleomycin-induced clastogenicity. These data give additional information to the knowledge of possible chemopreventive mechanisms of action of 13-cis-retinoic acid.

Antimutagenic Agents↗