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Biomedical subjects

T C Hsu

Publications and source records attributed to T C Hsu.

At least 127 records · Page 7Linked to original sources

Young adults with head and neck cancer express increased susceptibility to mutagen-induced chromosome damage.

Factors that contribute to an increased prevalence of squamous cell carcinoma of the upper aerodigestive tract among young adults in the United States remain unknown. A potential etiologic factor may relate to a genetically controlled sensitivity to environmental carcinogens. This study, therefore, examined 20 young adult patients who had squamous cell carcinoma for mutagen-induced chromosome sensitivity. Lymphocytes from respective patients were cultured, exposed to the clastogen bleomycin, arrested during metaphase, and examined quantitatively for chromosome breakage. As compared with an age- and sex-matched control population, as well as a population of patients who had non-squamous cell carcinoma head and neck tumors, the young adult population with squamous cell carcinoma expressed a significantly increased number of bleomycin-induced chromosome breaks per cell. Furthermore, among the study patients, chromosome sensitivity was most apparent in the non-tobacco users and in patients less than 30 years of age. The expression of such chromosome fragility following mutagen exposure should be considered in epidemiologic studies that intend to define risk factors for development of head and neck cancer.

Adult↗

Chromosome sensitivity to bleomycin-induced mutagenesis, an independent risk factor for upper aerodigestive tract cancers.

Defective DNA repair capability, measured by enumerating mutagen-induced chromosomal lesions, might explain variable host susceptibility to the action of environmental carcinogens. We compared sensitivity to bleomycin-induced chromosome damage in 75 patients (53 men and 22 women) with previously untreated upper aerodigestive tract malignancies with that in 62 healthy control subjects. Data on tobacco and alcohol use were derived from a detailed, self-administered cancer risk factor questionnaire. Forty-five patients and 13 controls were sensitive to bleomycin-induced mutagenesis (average breaks/cell greater than 0.8). Differential susceptibility was detected in patients categorized by primary tumor location. Odds ratios for chromosome sensitivity were significantly elevated for all sites (odds ratio = 10.3 for pharyngeal cancers, 8.0 for laryngeal cancers, and 3.8 for oral cavity cancers). On logistic regression analysis, chromosome sensitivity remained a strong and independent risk factor after adjustment for potential confounding from age, sex, and tobacco and alcohol use (odds ratio = 4.3, 95% confidence limits = 2.0, 10.2). Despite the small study size and design constraints, the strength of the association with chromosome sensitivity even after adjustment for potential confounders is impressive and suggests a promising avenue for further research. The preventive implications of a valid marker for carcinogen sensitivity are manifold.

Alcohol Drinking↗

Sensitivity to genotoxic effects of bleomycin in humans: possible relationship to environmental carcinogenesis.

Responses to the genotoxic effect of bleomycin in lymphocytes of blood cultures, expressed as the average number of chromatid breaks per cell (b/c), varied from less than 0.20 to more than 2.00 in 335 normal individuals. More than 11% of the subjects tested showed a b/c rate above 1.00 and more than 22% showed a b/c rate above 0.80. These individuals are considered sensitive to this radiomimetic drug. The distributional profile of bleomycin responses of the control individuals appears to be representative of the normal human population. In patients with cancers of the colon (83), upper aerodigestive tract (head/neck) (77), and lung (71), the frequencies of subjects in the hypersensitive class were found to be between 40 and 50%, and the response profiles were distinctly different from those of the control population. On the other hand, in a group of elderly cigarette smokers, who exhibited no symptoms of lung cancer, the bleomycin sensitivity profile was significantly skewed toward the more resistant stratum, with only one hypersensitive case among 56 individuals tested (1.78%). The sensitivity profile of patients with breast cancer (82) was similar to that of the control population. Our data suggest that: (1) mutagen sensitivity may play an important role in carcinogenesis of organs and tissues that have direct contact with the external environment (respiratory, digestive, and integumentary systems); (2) it appears to have no significant influence on carcinogenesis of tissues that are not directly exposed to the environment (e.g., breast, brain); and (3) it also has little impact on carcinogenesis in individuals with a hereditary predisposition to cancer (e.g., retinoblastoma, Gardner's syndrome). Development of more effective and precise test systems for carcinogen sensitivity is highly desirable for identification of persons at risk.

Adult↗

Traumatic perforation of ileal pouch. Report of a case.

A 28-year-old woman with a previous history of restorative proctocolectomy for complicated ulcerative colitis had acute onset of severe abdominal pain that was diagnosed at another hospital as a perforated peptic ulcer. Careful history-taking revealed that she had blunt trauma to the abdomen one day before admission. Laparotomy detected a perforation hole at the afferent loop of the ileal pouch. Debridement and primary closure of the perforation, with temporary decompression of the pouch, resulted in a good outcome. With the increasing popularity of selecting restorative proctocolectomy for the treatment of polyposis coli and ulcerative colitis, more and more pouches will be constructed. Possible perforation of the ileal pouch should be considered when such patients present with a perforated hollow viscus. With appropriate management, the pouch can be saved. Review of the literature revealed no similar reports.

Adult↗

Genotoxicity of [1H]benz[de]isoquinoline-1,3[2H]dione,5 amino-2-,[2-dimethylamino) ethyl] (BIDA) in human lymphocytes.

We have investigated the genotoxicity of BIDA in cultured human lymphocytes. Lymphocytes were cultured and stimulated with phytohemagglutinin (PHA) for 72 h. Doses of 0.1, 0.25, 0.5, 0.75, and 1 microgram/ml of BIDA were added to the culture at 1 h (G2 phase), and 6 h (S/G2 phase) before harvesting. Cells were harvested at the end of the 72-h culture period with 1-h colcemid treatment to accumulate mitosis, and further prepared by standard cytogenetic technique. BIDA induced chromatic type breakages and chromatid exchanges at both 1 h and 6 h. The mean number of breakages per cell was 0, 0.1, 1.0, and 1.7 after treatment with 0.1, 0.25, and 0.75 micrograms/ml, respectively. Ai 1 microgram/ml, BIDA severely inhibited cell progression and very few mitoses were observed. At 6 h the mean number of breakages per cell was 0.3 at 0.25 microgram/ml and 1.2 at 0.5 microgram/ml. Very few cells entered mitosis at 0.75 and 1 microgram/ml. To study the effect of BIDA on cells in G0 and G1, BIDA (0.75 microgram/ml) was added for 1 h to the cultures at the beginning of culture (G0), or 24 h after (G1) culture initiation. Afterward, cells were washed and reincubated in the conditioned medium for 71 or 47 h. No chromosomal aberrations were seen in these experiments. The number of chromatid breaks was minimal (0.1 to 0.4/cell). Our study suggests that BIDA induces chromatid type aberrations during G2 and S phases. The absence of chromosome type aberrations in cells treated during G0 and G1 suggests that either BIDA has no effect on these cells or that damaged cells fail to progress through S and G2 to reach mitosis.

Adenine↗

[Simultaneous cholecystectomy with colon surgery].

Both colorectal pathology and cholecystopathy are common disorders, especially among the elderly. Postoperative cholecystitis was well known to be associated with high morbidity and mortality. The presence of gall bladder pathology has also been reported to precipitate acute cholecystitis. In addition, these patients with gall bladder pathology may eventually need a cholecystectomy because of complications. In the above cases, some authors have suggested a simultaneous cholecystectomy at the time of colon surgery. In past 4 years, a series of 28 cases with concomitant cholecystectomy and colectomy were reviewed. The male to female ratio was 11:17, and their age ranged from 41 to 83 years old (mean age 61). The main colonic pathology was adenocarcinoma of colon and rectum (26/28). All gall bladder pathologies were diagnosed preoperatively by abdominal ultrasound, and gall stones were present in 25 of 28 cases. There were no intraoperative complications and no operative mortalities. Our data suggested that a cholecystectomy can be performed safely at the time of colon surgery, if the patient's condition is stable and contamination from colon surgery is minimal.

Adult↗

[Surface area--a new parameter for CMAP reading].

The purpose of this study is to determine a data range of the surface area of compound muscle action potential (CMAP) in normal abductor pollicis brevis and abductor digiti minimi. 256 median nerves and 317 ulnar nerves which were proved to be normal by NCV and EMG studies were included. Computer-aided measurement of distal latency, amplitude and nerve conduction velocity plus author-designed negative surface area reading was done. The surface areas of different age groups ranged from 28.6 to 35.3 ms*mV in abductor pollicis brevis and 30.0 to 31.5 ms*mV in abductor digiti minimi. There is no significant difference between different ages and between both sexes. The surface area showed statistically significant correlation with amplitude but no correlation with distal latency and nerve conduction velocity. It is concluded that as the concept of surface area is widely accepted and the measurement technique is more easily available, to set up a normal data base of surface area of the routinely examined muscle is very important and the surface area of CMAP should be included into the interpretation of routine nerve conduction studies.

Action Potentials↗

[Is synchronous hemorrhoidectomy with colonoscopy a worthwhile procedure?].

There were 201 patients receiving preoperative colonoscopy prior to hemorrhoidectomy in the meanwhile at MMH from July 1984 to June 1988. Other than rectal bleeding, they had colonic symptoms such as anemia, abdominal pain, familiar history of cancer and change of bowel habit etc. The study included 114 male and 87 female with ages ranging from 15 to 74 years (Median, 42 years). Three patients with colonic cancer and twenty-eight patients with neoplastic polyps were found by colonoscopic examination. Three cancer patients all received cancer surgery instead of hemorrhoidectomy as quickly as possible in a short time. One patient died for advanced stage and the other two patients got good results. The literatures were reviewed and discussed in accordance with the colonoscopic finding, operative time, hospital stay, post-operative morbidity and complication. There were not increase the postoperative morbidity in this series which compare with that of other series. The advantages of this procedure included: 1) Preventing suffer from twice colon preparations. 2) Preventing waiting period for Barium enema. 3) Preventing delay diagnosis of colorectal lesions especially colon cancer or precancer lesions of neoplastic polyps. 4) Performing examination and surgery at the same time-money-saving and time-saving. We thought synchronous hemorrhoidectomy with colonoscopy is a worthwhile clinical procedure.

Adolescent↗

[Mucocele of appendix-report of three cases].

Mucocele of appendix comprises 0.07%-0.3% of the resection of appendix. Three such cases were encountered over the past four years at MMH. Tumor mass could be palpated before operation in two of our cases. The third case was found incidentally during sigmoid cancer resection. Mucocele of the appendix should be differentiated from submucosal lesion such as leiomyoma, lipoma, lymphoma in the cecum or appendiceal abscess. Recent advances of ultrasound, CAT scan as well as angiography have made correct preoperative diagnosis possible, yet literature still shows diverse opinion about its etiology (neoplastic vs. obstructive). Although most authors favor simple appendectomy for the management of this disease, some surgeons still think it should be managed aggressively with colectomy. Rupture of mucocele might result in pseudomyxoma peritonei and possibly a fetal outcome. Avoidance of iatrogenic rupture of appendix is essential. Aggressive removal of accessible masses and implants was suggested in the literature.

Adult↗

Rate of generation of major karyotypic abnormalities in relationship to the metastatic potential of B16 murine melanoma.

To test the hypothesis that genetic instability correlates with malignant potential, we compared the rate of generation of marker chromosomal abnormalities in clones of B16 F1 and B16 F10 murine melanoma. These rates were estimated through an adaptation of fluctuation analysis of Luria and Delbruck (S. E. Luria and M. Delbruck, Genetics, 28: 491-511, 1943). The highly metastatic F10 line showed the same degree of marker chromosomal instability as the poorly metastatic F1 line (0.01 variants/cell/generation). When subclones of a karyotypically unstable F10 clone were compared with those of a more stable F10 clone, both groups caused the same number of pulmonary metastases, thus demonstrating a further lack of correlation of malignant potential with the level of genomic instability. Since measurements based on marker chromosomes may not truly reflect all of the changes detectable by G-banding, we also analyzed the G-banded karyotypes of the cell lines and their clones (chromatid or chromosomal breaks were not considered in this study). The F10 clones possessed an additional copy of chromosome 1 and also a significantly higher prevalence of the translocation t(9,12) when compared with the F1 clones. Rather than general rates of major karyotypic change determining tumor progression, we suggest the importance of other genetic or epigenetic mechanisms, particularly subtle nonrandom genetic or molecular changes, as the determining factors for malignant potential.

Animals↗

A mass vaccination program in Taiwan against hepatitis B virus infection in infants of hepatitis B surface antigen-carrier mothers.

To combat hepatitis B virus (HBV) infection in Taiwan, a mass immunoprophylaxis program was launched on July 1, 1984, aiming first at prevention of chronic HBV carriage from perinatal mother-to-infant infection. In the first 15-month period, 352,721 (78%) of 450,585 pregnant women were screened for hepatitis B surface antigen (HBsAg); HBsAg was present in 62,359 (18%), with 50% of them categorized as highly infectious. Infants born to HBsAg-positive women were given 5 micrograms of a plasma-derived hepatitis B vaccine at ages 1, 5, and 9 weeks, with a booster at age 12 months. Infants of highly infectious carrier mothers received an additional 0.5 mL of hepatitis B immune globulin within 24 hours after birth. The coverage rate of the hepatitis B immune globulin was 77% in 27,375 infants born to highly infectious mothers, and that of the first, second, third, and the fourth doses of vaccine was 88%, 86%, 84%, and 71%, respectively, in infants of 55,620 carrier mothers. The reported untoward reactions to immunization were negligible. We conclude that a mass hepatitis B vaccination program is feasible in hyperendemic areas such as Taiwan; this should be a significant step toward the effective control of HBV infection in these areas.

Carrier State↗

Mitotic inhibition and chromosome displacement induced by estradiol in Chinese hamster cells.

We tested diethylstilbestrol (DES) and 17 beta-estradiol as mitotic arrestants to determine their effects on chromosome distribution, spindle microtubules, and the cytoplasmic microtubule complex (CMTC) in the Chinese hamster strain Don. Cytological experiments assessed micronuclei induction, chromosome displacement, and anaphase recovery. Indirect immunofluorescence microscopy with antibody to tubulin and electron microscopy were used to illustrate effects on microtubules. Both DES and estradiol were potent inhibitors of mitosis when applied to cells in vitro. Estradiol induced micronuclei at a greater frequency than did DES. Estradiol-arrested metaphases often contained misaligned chromosomes despite the presence of a bipolar spindle and an equatorial plate. Equatorial plates were not observed in DES-arrested cells. Cells recovered quickly from estradiol exposure upon removal of the steroid. The frequency of abnormal metaphases and abnormal anaphases declined as the recovery period increased. Microtubule experiments showed that DES inhibited spindle assembly and disassembled the CMTC, whereas estradiol, at similar concentrations, arrested mitosis in a manner that allowed spindle assembly. A definite effect on the CMTC by estradiol could not be determined. However, changes in cell morphology were observed. In the presence of estradiol, centrosomes organized microtubules that joined with kinetochores of chromosomes at the equatorial plate as well as with those of misaligned chromosomes. Misaligned chromosomes appeared predominantly at polar regions of mitotic cells. Following drug removal, the pole-oriented chromosomes reoriented at the equatorial plate. The unique arresting properties of estradiol may prove useful in studies of chromosome migration and segregation during mitosis.

Anaphase↗

Genetic predisposition to cancer with special reference to mutagen sensitivity.

From studies on cancer genetics, available information suggests the following tentative conclusions: 1. Cancer starts with a genetic change (or changes) from a normal somatic cell, but the changes (mutational events) must be specific in a target tissue cell. In a number of cases, genetic changes can be detected at the chromosome level. 2. Hereditary cancers usually have one genetic lesion already existing prezygotically; therefore only one additional mutational event is required in the homologous gene to complete the process of neoplastic transformation. In nonhereditary neoplasms, both mutations must occur postzygotically. 3. Individuals with high spontaneous mutation rates (monitored by chromosome breakage rates) are more liable to acquire specific genetic lesions than those with low mutation rates; therefore they are at higher risk to develop neoplasms. 4. Individuals with genetic defects in response to damage induced by mutagens (carcinogens) are more liable to accumulate genetic lesions than those who are more resistant; therefore, they are more liable to develop cancers. Mutagen sensitivity or resistance is probably genetic expression of DNA repair capabilities. 5. An effective assay method for sensitivity or resistance to mutagens can be developed to analyze the human population to identify the at-risk fraction.

Chromosome Aberrations↗

Repeated tandem translocations in a clone and subclones of B16-F10 murine melanoma.

In one clone and three subclones isolated from the F10 line of the B16 mouse melanoma, a family of extraordinarily long marker chromosomes was found. Banding analyses showed that these long markers represented repeated tandem translocations. Most of these markers exhibited only two or three C-bands. Immunofluorescence staining using antikinetochore serum revealed that these markers had either two active kinetochores or one active and one inactive kinetochore. The original clone and one of the subclones were highly unstable with respect to the composition of the markers and to the ability for retaining the markers. The other two subclones were found to be relatively stable. Because all three subclones were derivatives of one clone, which was unstable, our data suggest that stable genomes can be generated from unstable progenitors.

Animals↗

Clonal origin of metastasis in B16 murine melanoma: a cytogenetic study.

A cell line isolated from the B16 melanoma and carried in continuous culture for 8 years (the parent line) exhibited great heterogeneity in terms of marker chromosome content. A lung metastasis from a C57BL/6 mouse inoculated im with cells of this line showed karyotypic homogeneity. Inoculation iv of cells from the parent line produced numerous tumor foci in various organs. Cytogenetic analyses of 18 such lesions led to the following conclusions: Cells from each metastatic colony exhibited relatively homogeneous karyotypic characteristics, indicating that metastases are of clonal origin; many parental cells with different marker chromosomes had metastatic potential; and some genomes maintained homogeneity longer than others.

Aneuploidy↗