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Biomedical subjects

T C Hsu

Publications and source records attributed to T C Hsu.

At least 55 records · Page 3Linked to original sources

Molecular cloning of platelet factor XI, an alternative splicing product of the plasma factor XI gene.

Platelet factor XI is associated with the platelet plasma membrane and has an apparent Mr (220,000 nonreduced, 55,000 reduced) different from that of plasma factor XI. However, the site of synthesis and the nature of platelet factor XI are not known. Using reverse transcriptase polymerase chain reaction, 12 out of 13 exons (all except exon V) coding for mature plasma factor XI were amplified from human platelet mRNA. The sequence of each of these exons was identical to that of plasma factor XI. In situ amplification and hybridization of factor XI mRNA was positive for exon III and negative for exon V in platelets and negative for both exons in other blood cells. By Northern hybridization, a factor XI mRNA transcript of approximately 1.9 kilobases was detected in megakaryocytic cells, and one of approximately 2.1 kilobases was detected in liver cells. Factor XI cDNA was cloned from a megakaryocyte library and sequenced. Exon V was absent, and the splicing of exon IV to exon VI maintained the open reading frame without alteration of the amino acid sequence except for the deletion of amino acids Ala91-Arg144 within the amino-terminal portion of the Apple 2 domain. Thus, platelet factor XI is an alternative splicing product of the factor XI gene, localized to platelets and megakaryocytes but absent from other blood cells.

Alternative Splicing↗

Sonographic detection of a stitch abscess.

A 28-year-old man with a ruptured right Achilles tendon underwent primary end-to-end suture immediately after injury. Painful swelling developed 6 months later, and a lump with discharge from a sinus was observed during physical assessment. Sonographic examination with a 10-MHz linear-array transducer demonstrated a hypoechoic mass, 8 x 6 mm, within which were 2 markedly echogenic dots. A stitch abscess was strongly suspected and was confirmed surgically.

Abscess↗

One-stage resection and anastomosis for acute obstruction of the left colon.

PURPOSE: The purpose of this study was to analyze a single surgeon's experience with one-stage resection with primary anastomosis in acute obstruction of the left colon, emphasizing intraoperative decompression before the anastomosis. METHOD: From January 1986 to September 1996, 91 patients received one-stage resection with primary anastomosis for acute obstruction of the left colon. Eighty-five of these 91 patients were operated on for carcinoma of the colon and rectum. Subtotal colectomies were performed in 20 patients, left hemicolectomies in 21 patients, sigmoid colectomies in 34 patients, and anterior resections in 16 patients. The preoperative serum albumin level was less than 3 gm/dl in 17 patients (less than 2.5 gm/dl in 10 patients). Four patients had associated abscesses, and one patient had colonic perforation with peritonitis before operative colonoscopy. Neither antegrade nor retrograde irrigation was performed. RESULTS: Operative mortality rate was 2.2 percent. There were two cases (2.2 percent) of anastomotic leakages. Other common complications included wound infection (11 cases), urinary tract infection (5 cases), intestinal obstruction (6 cases), and respiratory failure (3 cases). CONCLUSION: This experience suggests that an anastomosis can be performed more safely in patients with acute obstruction of the left colon than in those with an anastomosis in the nondiverted colon. Neither intraoperative irrigation nor routine subtotal colectomy was found to be necessary. Anastomosis below the peritoneal reflection is also not a contraindication.

Adult↗

Comparison of the mechanical properties of the heel pad between young and elderly adults.

OBJECTIVE: To compare the mechanical properties of the human heel pad between young and aged adults. DESIGN: A 7.5-MHz linear-array ultrasound transducer was incorporated into a specially designed device to measure the thickness of the heel pad under different loads. The heel pad was compressed with serial increments of 0.5kg to a maximum of 3kg and then relaxed sequentially. Then the load-displacement curve of the heel pad during a loading-unloading cycle was plotted. PARTICIPANTS: Convenience sample of 33 volunteers without heel problems, aged 18 to 78 years, were divided into young (less than 40 years) and elderly (older than 60 years) groups. MAIN OUTCOME MEASURES: Unloaded heel-pad thickness, compressibility index, stiffness, and energy dissipation ratio were calculated from the load-displacement curves. Student's t-test was used to compare the mechanical properties of the heel between these two groups. RESULTS: The average unloaded heel-pad thickness was 1.76+/-.20cm in the young group and 2.01+/-.24cm in the elderly group (p < .001). The average compressibility index was 53.3%+/-7.7% in the young group and 61.3%+/-5.5% in the elderly group (p < .001). Energy dissipation ratio representing shock absorbency of the heel pad, was 23.7%+/-6.9% in the young group and 35.3%+/-10% in the elderly group (p < .001). CONCLUSION: Unloaded heel-pad thickness, compressibility index, and energy dissipation ratio of the heel pad were significantly increased in the elderly group, indicating loss of the elasticity of the heel pad. The loss of elasticity may be responsible for the higher incidence of heel injury in elderly individuals.

Adolescent↗

Ileal penetration by a Multiload-Cu 375 intrauterine contraceptive device. A case report with review of the literature.

A case of a 28-year-old gravida 3 para 2 woman with an ileal penetration by an intrauterine device (IUD) is reported. Four weeks following insertion of a Multiload-Cu 375, the woman underwent laparotomy due to persistent vague abdominal pain and translocation of the IUD. The device had perforated the fundal uterine wall and the two flexible side arms and the copper-bearing rod had completely eroded into the wall of the ileum with only the strings protruding outside the small bowel mesentery. Resection of an ileal segment with end-to-end anastomosis was performed. The woman made an uneventful recovery. It appears that a translocated Multiload-Cu 375 IUD body can penetrate and be entirely embedded within the bowel wall as early as 4 weeks following translocation. This report documents the shortest interval between insertion and proven bowel injury by an IUD.

Adult↗

Deletion in poly(ADP-ribose)polymerase pseudogene and lung cancer risk.

The poly(ADP-ribose)polymerase (PADPRP) gene has been implicated in carcinogenesis through its role in DNA repair, replication and recombination. A two-allele polymorphism in the chromosome 13 PADPRP pseudogene has been studied in several racial groups. It has been suggested that the B allele, which results from a 193-bp deletion in the gene, predisposes to myeloma in Blacks. We assessed the association between chromosome 13 PADPRP pseudogene genotype, mutagen sensitivity (a marker reflecting host DNA repair capability), cigarette smoking, and lung cancer risk in a minority lung cancer case-control study. The chromosome 13 PADPRP pseudogene polymorphism was detected by polymerase chain reaction-based analysis. Mutagen sensitivity was measured by an in vitro assay that quantified bleomycin-induced chromatid breaks in peripheral blood lymphocyte cultures. We examined 121 cases (80 African-Americans and 41 Mexican-Americans) with previously untreated lung cancer and 171 matched controls. Our results suggested that the distribution of the PADPRP pseudogene genotype frequencies was significantly different among African-American and Mexican-American controls (P < 0.001). The susceptibility genotype (i.e. at least one B allele) was found in 82.5% of African-American cases, 79.4% of African-American controls, 53.7% of Mexican-American cases, and 32.4% of Mexican-American controls. The odds ratios (OR) and 95% confidence intervals for the PADPRP susceptibility genotypes were 2.3 (95% CI = 0.7-8.0) and 3.2 (95% CI = 1.0-10.3) for African-Americans and Mexican-Americans respectively, after adjustment by age, sex, pack-years and mutagen sensitivity. Patients with the susceptibility genotype appeared to have more mutagen-induced breaks than did patients with the other genotype. Only adenocarcinoma was significantly associated with the PADPRP susceptibility genotype (OR = 3.8). Mutagen sensitivity (> or = 1 break/cell) was significantly associated with lung cancer risk for both ethnic groups with increased ORs of above three-fold. On stratified analysis, synergistic interactions were noted for the PADPRP susceptibility genotype, mutagen sensitivity and smoking status. In Mexican-Americans, the ORs for PADPRP susceptibility genotype, mutagen sensitivity and both risk factors combined were 1.3, 2.7 and 17.1 respectively. The combined OR for the PADPRP susceptibility genotype and smoking status was 15.6. Therefore, this polymorphism appears to be associated with lung cancer risk. However, it is likely that no single genotype is sufficiently predictive of risk and that a panel of susceptibility markers is needed to define the high-risk subgroup.

Black People↗

Exaggerated precocious centromere separation in cells of a human breast cancer line treated with a green tea extract.

In a breast cancer cell line, MDA-MB-468, established in our laboratory, an average of 3% of the mitotic cells exhibited a phenomenon known as centromere splaying, which is a characteristic feature of cells of patients with Roberts syndrome. However, centromere splaying in cells of Roberts syndrome patients is limited to i) the centromere region and ii) chromosomes with large amounts of heterochromatin. When the breast cancer cells were treated with an extract of green tea GTE-TP91, up to 45% of the metaphases were observed to exhibit this behavior; and the precocious centromere separation was highly exaggerated, affecting all chromosomes in such metaphases. Apparently, as the sister centromeres continued to pull apart, they carried the chromatids with them, except for the telomere regions, giving a ring-like configuration. Eventually, the sister chromatids became completely separated. Whether this bizarre phenomenon was induced by the polyphenols contained in this green tea extract GTE-TP91 is not known, but this phenomenon, upon further investigation, may throw some light on chromosomal proteins, centromere behavior, telomere behavior and related questions.

Breast Neoplasms↗

Effects of beta-carotene and alpha-tocopherol on bleomycin-induced chromosomal damage.

The number of bleomycin-induced chromosomal breaks in cultured peripheral blood lymphocytes has been proposed as a measure of the sensitivity of an individual to carcinogens. Although "mutagen sensitivity" (clastogenicity) may be a useful biomarker for the identification of individuals at high risk for DNA damage, there is some uncertainty whether the results of this assay can be modified by environmental factors, such as diet. We designed an intervention study to determine whether micronutrient supplementation with beta-carotene and alpha-tocopherol influenced the mutagenicity score among 22 healthy volunteers. This intervention study followed a double-blind, randomized, cross-over design. Chromatid breaks ranged from 0.30 to 2.30 per cell and were uncorrelated with plasma beta-carotene (r = -0.07; P = 0.50) and a-tocopherol (r = -0.01; P = 0.92) levels, after accounting for the time of the measurement. The average number of breaks per cell was similar (P for difference in means = 0.90) among subjects during periods of vitamin supplementation (mean = 0.87 breaks per cell) and placebo (mean = 0.86 breaks per cell), averaged over groups and after adjustment for baseline breaks. Substantial within-person variation may indicate some imprecision in the mutagen sensitivity assessment. Our results suggest that mutagen sensitivity is not affected by plasma levels of beta-carotene or alpha-tocopherol. Although mutagen sensitivity does not appear to be modified by changes in plasma levels of two common antioxidant vitamins, it may be useful for the identification of high-risk individuals for participation in large intervention studies with cancer outcomes.

Adult↗

DNA repair and mutagen sensitivity in patients with triple primary cancers.

The purpose of this study was to measure DNA repair capacity and mutagen sensitivity in patients who have had three or more primary forms of cancer. It was hypothesized that, if abnormalities in DNA repair and mutagen sensitivity were cancer susceptibility factors, such findings would be seen with regularity in individuals with multiple primary cancers. DNA repair capacity was measured by determining repair of UV-irradiated plasmid DNA (pCMVCAT) transfected into peripheral blood lymphocytes. Results from 18 patients and a like number of age- and sex-matched controls demonstrated a significant difference in DNA repair capacity (P < 0.0001; odds ratio = 14). Mutagen sensitivity was measured by determining the mean number of chromatid breaks per cell after in vitro exposure to either bleomycin or 4-nitroquinoline-1-oxide. The difference in mean bleomycin- or 4-nitroquinoline-1-oxide-induced mutagen sensitivity between cases and controls was not statistically significant. Fourteen of the 18 patients had positive family histories of cancer; in 10, the history was compatible with cancer susceptibility syndromes. Although the numbers were small, there was no suggestion in this study that treatment or the presence of cancer was the cause of the DNA repair abnormalities encountered. These findings support the concept of diminished DNA repair capacity as an underlying feature in the development of a mutator phenotype.

4-Nitroquinoline-1-oxide↗

Variations in heel pad mechanical properties variation between children and young adults.

The purpose of this study was to compare the mechanical properties of the heel pads of adults and children, using ultrasound to assess the responses of the heel pad during compression. Thirty volunteers without heel problems, aged from 4 to 36 years, were recruited. There were 10 children (< 15 years old) and 20 adults (> 18 years old). A 7.5-MHz linear array ultrasound transducer was incorporated into a specially designed device to measure the thickness of the heel pad under different loads. The load on the heel pad was increased serially in increments of 0.5 kg, to a maximum of 3 kg, and then reduced sequentially. The load-displacement curve of the heel pad during a loading-unloading cycle was then plotted. Mechanical properties of the heel, including unloaded heel-pad thickness (UHPT), compressibility index, elastic modulus, and energy dissipation ratio (EDR), were calculated from the load-displacement curves. The average UHPT was 1.53 +/- 0.09 cm in children and 1.76 +/- 0.20 cm in adults (p < 0.001). The EDR, which represents the shock absorbency of the heel pad, was 13.5 +/- 2.0% in the children and 23.7 +/- 6.9% in adults (p < 0.001). The average compressibility index and elastic modulus were also higher in adults than in children, although the differences were not statistically significant. These findings suggest that the mechanical properties of the heel pad change from childhood to adulthood. Less energy is absorbed in the heel pad of children, which may partially explain why children tend to have fewer heel problems than adults.

Adolescent↗

Neuropsychological sequelae after treatment for medulloblastoma in childhood--the Taiwan experience.

The purpose of this study was to investigate the functional independence, intellectual performance and academic achievement of children treated for medulloblastoma at the Veterans General Hospital-Taipei. Adverse factors that it was thought would result in significant intellectual impairment were also studied. Nineteen patients with medulloblastoma located over the posterior fossa were enrolled in this study. Their mean age at tumor removal was 6.16 +/- 3.30 (range 2-14) years. Mean full intelligent quotient (FIQ) was 86.00 +/- 22.66, performance intelligent quotient (PIQ) was 85.29 +/- 21.23, and verbal intelligent quotient (VIQ) was 90.50 +/- 23.50. In 11 cases academic achievement at school was poor. Sixteen patients received radiation therapy after tumor removal. Significant negative correlations were noted between IQ and whole-brain irradiation dose (r = -0.72) and between IQ and years after radiation therapy (r = -0.63). The results indicate a need for ongoing attention and intervention to prevent, remedy or minimize deficits produced by the tumor itself and by the cancer treatment.

Achievement↗

Autoantigen components recognizable by scleroderma sera are exported via ectocytosis of fibroblasts.

Previously, we have demonstrated that ectocytosis, a unique cell trafficking process to export a specific subset of cellular proteins in the form of membrane vesicles, can be triggered from human skin fibroblasts cultured in a three-dimensional collagen lattice upon stress relaxation. The same culturing system was employed in the present study using fibroblasts isolated from patients with systemic sclerosis (SSc). To see whether any putative intracellular autoantigens causing SSc might escape out of cells by way of ectocytosis, the same stress-relaxation method was used to induce a synchronized ectocytosis among cultured cells. Membrane vesicles released by scleroderma fibroblasts were subsequently isolated, resolved on SDS-PAGE and immunoblotted with sera from 89 patients with various autoimmune diseases and 11 normal volunteers. Three major polypeptides with apparent mol. wts of 12-14, 32-34 and 70-80 kDa are prominent bands on both SDS-PAGE and immunoblots. The 32-34 kDa polypeptide has been further identified as a member of the annexin protein family, while the 70-80 kDa protein has been shown to be topoisomerase I, as judged by its reactivity to patients' sera and a rabbit polyclonal antibody, and as also judged by a functional assay. In conclusion, our results suggest that ectocytosis might be one of the potential pathways for cells to export intracellular antigens and subsequently cause autoimmune reactions.

Animals↗

Genetic susceptibility to head and neck cancer: interaction between nutrition and mutagen sensitivity.

The development of head and neck cancer may depend not only on exposure to environmental carcinogens but also on a genetically based susceptibility to carcinogen-induced damage. This thesis presents a case-control study that demonstrates the significance of mutagen sensitivity, a measure of an individual's intrinsic DNA repair capacity against free radical damage, as a risk factor for the disease. As part of the case-control analysis, 167 previously untreated patients and 177 age- and sex-matched healthy controls were assessed for various lifestyle factors including tobacco and alcohol habits, occupational exposures, and diet. Mutagen sensitivity expressed by each individual was determined by quantifying bleomycin-induced chromosomal breaks within peripheral blood lymphocytes in vitro. Consistent with our initial observations and those of others, mutagen hypersensitivity was strongly associated with increased risk of head and neck cancer (odds ratio, 4.95; 95% confidence interval, 2.67 to 9.17) after adjusting for age, sex, and race. Low intake of vitamins C and E was also associated with an increased risk of disease and was interactive with mutagen sensitivity in risk estimates. Individuals with both a low intake of various antioxidants and increased chromosomal sensitivity to oxidant-induced DNA damage were at greatest risk. This study supports the concept that the risk of head and neck cancer is determined by a balance of factors that either enhance or protect against free radical oxygen damage, including innate capacities for DNA repair.

Adult↗

Epidemiologic survey of lower urinary tract symptoms in Asia and Australia using the international prostate symptom score.

BACKGROUND: The prevalence of lower urinary tract symptoms was determined by survey as an initial step in estimating the significance of benign prostatic hyperplasia (BPH) in Asia and Australia. METHODS: The symptom index (0 to 35) and quality-of-life (QOL) index (0 to 6) of the international prostate symptom score were measured in 7588 men in 9 Asian countries and 146 men in Australia. RESULTS: The percentages of Asian men considered to be symptomatic (symptom index > or = 8) were 18%, 29%, 40%, and 56% in the age groups of 40 to 49, 50 to 59, 60 to 69, and 70 to 79 years, respectively. For Australian men, these figures were 36%, 33%, and 37% in the 50 to 59, 60 to 69, and 70 to 79 year age groups, respectively. CONCLUSIONS: Our estimates indicate that the prevalences of symptomatic men in Asia and Australia are similar to or greater than those in Europe and America, and suggest BPH is similarly common in these areas.

Adult↗

Ultrasonographic examination of the posterior tibial tendon.

The posterior tibial tendons (PTTs) of 16 patients with PTT dysfunction and 10 age-matched healthy subjects were examined ultrasonographically, using a 10-MHz linear-array transducer. Normal PTTs appeared hyperechoic (more echogenic) and oval, with an average diameter of 7.8 mm x 3.7 mm at the medial malleolar level. Degenerated PTTs appeared hypoechoic (less echogenic) and swollen (9.8 mm x 5.0 mm). Peritendinitis presented as a hypoechoic rim on the longitudinal sonogram (along the long axis of the tendon) and a "target sign" (hyperechoic central structure with a hypoechoic halo) on the transverse sonogram (at the right angle to the long axis of the tendon). Complete rupture of the PTT revealed an empty tibial groove at the level of the medial malleolus on the transverse sonogram and a wavy fibril pattern over the distal end on the longitudinal sonogram. Compared with the operative findings or the results of the magnetic resonance imaging, ultrasonography was sensitive and specific in diagnosing tenosynovitis and complete rupture of the PTT.

Ankle↗

A clinical trial to evaluate the effect of vitamin C supplementation on in vitro mutagen sensitivity. The University of Texas M. D. Anderson Clinical Community Oncology Program Network.

Mutagen sensitivity, as measured by an in vitro assay, has been described as a risk factor for the development of several tobacco-related epithelial cancers. In vitro studies have indicated that sensitivity to the clastogenic effects of bleomycin on chromosomes was reduced with the introduction of ascorbic acid in a dose-dependent relationship. We report the results of a randomized clinical trial to determine whether increasing levels of oral ascorbic acid could reduce the levels of mutagen sensitivity. For this study, we recruited 228 healthy smokers from 21 centers around the country through the Clinical Community Oncology Program. Each individual was randomly assigned to one of four daily regimens: placebo, 1 g of ascorbic acid, 2 g of ascorbic acid, or 4 g of ascorbic acid. Treatments were administered for 16 weeks. Assessment of mutagen sensitivity was made at baseline and at weeks 4, 16, and 20 (4 weeks after cessation of treatment). Serum ascorbic acid levels were measured at baseline and at weeks 4 and 16. Demographic and risk factor data were collected at baseline and at each-measurement point. Analyses measured the differences of mutagen sensitivity levels across the four treatment arms, as well as investigating the correlation between serum ascorbic acid level and mutagen sensitivity levels in individuals. We did not find a dose-response relationship between ascorbic acid intake and mutagen sensitivity. Additionally, we did not find an association between serum ascorbic acid levels and mutagen sensitivity.

Administration, Oral↗