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Biomedical subjects

T C Yang

Publications and source records attributed to T C Yang.

At least 37 records · Page 2Linked to original sources

Estimate of true incomplete exchanges using fluorescence in situ hybridization with telomere probes.

PURPOSE: To study the frequency of true incomplete exchanges in radiation-induced chromosome aberrations. MATERIALS AND METHODS: Human lymphocytes were exposed to 2 Gy and 5 Gy of gamma-rays. Chromosome aberrations were studied using the fluorescence in situ hybridization (FISH) technique with whole chromosome-specific probes, together with human telomere probes. Chromosomes 2 and 4 were chosen in the present study. RESULTS: The percentage of incomplete exchanges was 27% when telomere signals were not considered. After excluding false incomplete exchanges identified by the telomere signals, the percentage of incomplete exchanges decreased to 11%. Since telomere signals appear on about 82% of the telomeres, the percentage of true incomplete exchanges should be even lower and was estimated to be 3%. This percentage was similar for chromosomes 2 and 4 and for doses of both 2 Gy and 5 Gy. CONCLUSIONS: The percentage of true incomplete exchanges is significantly lower in gamma-irradiated human lymphocytes than the frequencies reported in the literature.

Chromosome Aberrations↗

The effect of track structure on the induction of chromosomal aberrations in murine cells.

PURPOSE: To measure chromosome aberrations in C3H 10T1/2 mouse fibroblasts using FISH painting at the first mitosis following exposure to 30 keV/microm hydrogen or neon ions. MATERIALS AND METHODS: Cells in plateau-phase were irradiated with 0.86 MeV protons at the TTT-3 Tandem accelerator in Naples (Italy), or with 400 MeV/n Ne ions at the HIMAC accelerator in Chiba (Japan). Colcemid-blocked cells were harvested at the first mitosis following exposure, and chromosome spreads were hybridized in situ with a fluorescein-labelled composite mouse DNA probe specific for chromosomes 2 and 8. RESULTS: Protons were more efficient than neon ions at the same LET in the induction of chromosome interchanges and breaks. Yields of complex exchanges were similar for both particles at the same dose, but protons produced mostly insertions, while with Ne exposure non-reciprocal exchanges were the most frequent complex-type exchange. CONCLUSIONS: Charged particles with the same LET produce different yields of chromosome aberrations, and some observed differences can be explained based on the available track-structure models.

Animals↗

Radiation-induced total-deletion mutations in the human hprt gene: a biophysical model based on random walk interphase chromatin geometry.

PURPOSE: To develop a biophysical model that explains the sizes of radiation-induced hprt deletions. METHODS: Key assumptions: (1) Deletions are produced by two DSB that are closer than an interaction distance at the time of DSB induction; (2) Interphase chromatin is modelled by a biphasic random walk distribution; and (3) Misrejoining of DSB from two separate tracks dominates at low-LET and misrejoining of DSB from a single track dominates at high-LET. RESULTS: The size spectra for radiation-induced total deletions of the hprt gene are calculated. Comparing with the results of Yamada and coworkers for gamma-irradiated human fibroblasts the study finds that an interaction distance of 0.75 microm will fit both the absolute frequency and the size spectrum of the total deletions. It is also shown that high-LET radiations produce, relatively, more total deletions of sizes below 0.5 Mb. The model predicts an essential gene to be located between 2 and 3 Mb from the hprt locus towards the centromere. Using the same assumptions and parameters as for evaluating mutation frequencies, a frequency of intra-arm chromosome deletions is calculated that is in agreement with experimental data. CONCLUSIONS: Radiation-induced total-deletion mutations of the human hprt gene and intrachange chromosome aberrations share a common mechanism for their induction.

Biophysical Phenomena↗

Rejoining and misrejoining of radiation-induced chromatin breaks. III. Hypertonic treatment.

It has been shown that treatment in anisotonic medium modifies rejoining of radiation-induced breaks in interphase chromosomes. In previous work, we have demonstrated that formation of exchanges in human lymphocytes has a slow component (half-time of 1-2 h), but a fraction of exchanges are also observed in samples assayed soon after exposure. In this paper we studied the effect of hypertonic treatment on rejoining and misrejoining of radiation-induced breaks using fluorescence in situ hybridization of prematurely condensed chromosomes in human lymphocytes. Isolated lymphocytes were irradiated with 7 Gy gamma rays, fused to mitotic hamster cells and incubated in hypertonic solution (0.5 M NaCl) for the period normally allowed for interphase chromosome condensation to occur. The data from hypertonic treatment experiments indicate the presence of a class of interphase chromosome breaks that rejoin and misrejoin very quickly (half-time of 5-6 min). The fast misrejoining of these lesions is considered to be responsible for the initial level of exchanges which we reported previously. No significant effect of hypertonic treatment on the yield of chromosome aberrations scored at the first postirradiation mitosis was detected.

Animals↗

Acute pancreatitis in pregnancy.

BACKGROUND: Acute pancreatitis in pregnancy is rare. Our purpose in this study was to discuss the etiology, incidence and course of pancreatitis in pregnancy and to evaluate the maternal and perinatal outcomes. METHODS: Pregnant women with pancreatitis admitted to China Medical College Hospital, Taiwan, from 1980 to 1995 were studied retrospectively. A total of 16 patients were enrolled in the study. Two patients had gallstones and hyperlipidemia; four had gallstones alone; seven had hyperlipidemia alone; one had gestational diabetes mellitus; one had hyperparathyroidism and pregnancy-induced hypertension alone; and one had Hashimoto's thyroiditis. Conservative treatment and low-fat diets were administered to the patients. RESULTS: The incidence of gestational pancreatitis in this series was one in 6,790 pregnancies. The fetal outcome included eight preterm deliveries and three fetal losses. There were no maternal mortalities. The etiologies of pancreatitis were primary hyperlipidemia (56.3%) and gallstones (37.5%). All patients responded favorably to supportive therapy, and most of the symptoms subsided after delivery. CONCLUSIONS: Early diagnosis and treatment is of utmost importance in the management of acute pancreatitis in pregnancy. The results of this study showed good maternal outcome following appropriate treatment. Fetal prognosis was less favorable and was most often associated with hyperlipidemia. Fetal monitoring is essential during the management of pancreatitis in pregnancy.

Acute Disease↗

Rejoining and misrejoining of radiation-induced chromatin breaks. IV. Charged particles.

We have recently reported the kinetics of chromosome rejoining and exchange formation in human lymphocytes exposed to gamma rays using the techniques of fluorescence in situ hybridization (FISH) and premature chromosome condensation (PCC). In this paper, we have extended previous measurements to cells exposed to charged particles. Our goal was to determine differences in chromatin break rejoining and misrejoining after exposure to low- and high-linear energy transfer (LET) radiation. Cells were irradiated with hydrogen, neon, carbon or iron ions in the LET range 0.3-140 keV/microm and were incubated at 37 degrees C for various times after exposure. Little difference was observed in the yield of early prematurely condensed chromosome breaks for the different ions. The kinetics of break rejoining was exponential for all ions and had similar time constants, but the residual level of unrejoined breaks after prolonged incubation was higher for high-LET radiation. The kinetics of exchange formation was also similar for the different ions, but the yield of chromosome interchanges measured soon after exposure was higher for high-LET particles, suggesting that a higher fraction of DNA breaks are misrejoined quickly. On the other hand, the rate of formation of complete exchanges was slightly lower for densely ionizing radiation. The ratios between the yields of different types of aberrations observed at 10 h postirradiation in prematurely condensed chromosome preparations were dependent on LET. We found significant differences between the yields of aberrations measured in interphase (after repair) and metaphase for densely ionizing radiation. This difference might be caused by prolonged mitotic delay and/or interphase death. Overall, the results point out significant differences between low- and high-LET radiation for the formation of chromosome aberrations.

Animals↗

Intramural pregnancy with negative maternal serum beta-hCG. A case report.

BACKGROUND: Intramural pregnancy is the rarest form of ectopic pregnancy. The diagnosis depends upon the sonographic finding of intramural gestational sac-like growth and persistent high beta-human chorionic gonadotropin (beta-hCG) levels after dilatation and curettage. No authors mentioned negative beta-hCG result in such situation. Rarely has the literature contained preoperative sonograms and photographs of postoperative gestational tissue. CASE: A 31-year-old woman presented with vaginal spotting for five months. Six months earlier she underwent dilatation and curettage for blighted ovum at 8 weeks' gestation. Since then, incidental vaginal spotting was noted. Sonography demonstrated an intramural cyst with fetal pole-like growth. Serum beta-hCG, diagnostic dilatation and curettage, and hysteroscopic examination were negative. Laparotomy for excision of the cyst confirmed an intramural pregnancy. CONCLUSION: Because of the long period after fetal wastage, negative serum beta-hCG was noted in this case. Negative serum beta-hCG was unreliable in the exclusion of intramural pregnancy. With the sonographic appearance of intramural gestational sac-like growth, in spite of a negative serum beta-hCG the clinician should be alert to the possibility of intramural pregnancy.

Adult↗

Malignancy following renal transplantation.

BACKGROUND: A markedly increased incidence of malignancy in transplant recipients is well recognized. However, the incidence and pattern of post-transplantation malignancies shows some discrepancy among different reports. The renal transplant recipients monitored at Taichung Veterans' General Hospital comprise the largest group in Taiwan. An analysis of the characteristics of post-transplant malignancies emphasizes the differences from malignancies that occur in the Taiwanese general population and those reported in Western countries. METHODS: The incidence and characteristics of de novo malignancy in 390 renal transplant recipients who underwent renal transplantation between May 1983 and June 1996 were analyzed. A total of 232 men and 158 women (mean age at transplantation: 38.5 +/- 10.7 years) were included. The relative risk for developing malignancies was calculated based on the sex- and age-matched cancer incidence of reference for the Taiwanese population; data from the Cancer Registry Annual Report in Taiwan (1989) was obtained for comparison. RESULTS: A total of 25 cancers were diagnosed in 24 renal transplant recipients, for an incidence of 6.2%. The relative risk of renal malignancy was 13.8-fold higher among transplant recipients than in the general population. The impact of gender and age on the development of post-transplantation malignancy was not significant. The most common types of cancer were transitional cell carcinoma (TCC) of the urinary tract (8/25), and hepatoma (8/25), followed by two cases of Kaposi's sarcoma. Aside from immunosuppressive agents, the high incidence of hepatoma and TCC may be attributed to the high incidence of hepatitis infection and the possible carcinogenic effect of abnormal milieu induced by uremia per se. Survival was largely dependent on the extent of disease at presentation, and post-transplantation cancer did not show more aggressive behavior if detected early. CONCLUSIONS: The high cumulative incidence of malignancies makes it imperative to define an effective safe immunosuppressive regimen to achieve a lower risk of malignancies. In the future, the prime approach to treatment of post-transplantation malignancies should begin with early detection and ensuing aggressive treatment to improve the outcome.

Adolescent↗

Rupture of rudimentary horn pregnancy: a case report.

A rare case of rupture of a noncommunicating rudimentary horn pregnancy is presented. The pregnancy continued to 16-weeks' gestation, when the rudimentary horn ruptured. The patient had signs and symptoms of massive hemoperitoneum. An emergency exploratory laparotomy revealed a ruptured rudimentary horn and an intact amnionic sac. Prompt excision of the rudimentary horn was performed. The relative literature and factors associated with a rudimentary horn pregnancy are reviewed and discussed.

Adult↗

Prenatal diagnosis of Apert syndrome.

Apert syndrome (AS) is clinically characterized by typical facial features and symmetrical syndactyly of the digits. AS is inherited as an autosomal dominant trait. Recently, a fibroblast growth factor receptors 2 (FGFR2) mutation, either C934G or C937G, was identified in exon IIIa. Our report documents an affected mother and son in whom one of the two mutations in AS had occurred sporadically in the mother. The diagnosed of AS was based on associated abnormal physical features and on molecular genetic analysis. A C-to-G transversion at position 937 of the cDNA resulting in a proline-to-arginine substitution at codon 259 was found in the mother. In her second pregnancy, prenatal diagnosis by both restriction analysis and direct sequencing was undertaken and this showed that the female fetus had not inherited the mutation.

Acrocephalosyndactylia↗

Succinylcholine-induced cardiac arrest in unsuspected becker muscular dystrophy--a case report.

A five year-old boy undergoing elective tonsillectomy sustained cardiac arrest following the administration of a single dose of succinylcholine during induction of anesthesia. With a 10-minute cardiopulmonary resuscitation (CPR) during which intravenous calcium gluconate, epinephrine, and sodium bicarbonate were given and DC counter shock applied, we were successful to restore cardiac activity without neurological sequelae. The cause of cardiac arrest we speculated was hyperkalemia, possibly secondary to succinylcholine-induced rhabdomyolysis. It is suggested that succinylcholine should not be used in patients with known or suspected muscular dystrophy.

Child, Preschool↗

Unexpected pheochromocytoma--a case report of anesthesia in a uremic patient.

Pheochromocytoma is an uncommon neoplasm causing blood pressure changes. It may go undiagnosed in uremic patients in whom hypertension is common. The preferential diagnostic work-up, including urine and serum catecholamine measurements, is unsuitable for uremic patients due to anuria and inherent increases in serum catecholamine levels. Here, we present a case of uremia, scheduled for right adrenalectomy and simple nephrectomy, who had been sustaining hypertension. Malignant hypertension was only discovered during surgical manipulation of the adrenal tumor. Pheochromocytoma was highly suspected. The patient was treated with nitroglycerin, fentanyl, and increased concentration of isoflurane to deepen the anesthesia. However, the results were only fair and after ligation of the tumor veins, hypotension ensued. Pathological examination verified the diagnosis of pheochromocytoma. In reviewal of the whole course of treatment, it was considered that the placement of a pulmonary artery catheter to detect volume shifts and changes in hemodynamic status was indicated. Related papers were reviewed and application of diagnostic tools and their limitations, safety and efficacy of anesthetics and vasodilators, and possible complications relevant to management of pheochromocytoma were also discussed. In conclusion, it is important to remain alert, administer agents cautiously, and set up complete monitoring if needed, and carry out postoperative intensive care to lessen complications in the anesthetic management of this rare and dangerous incidentaloma encountered during anesthesia.

Adrenal Gland Neoplasms↗

Initiation of oncogenic transformation in human mammary epithelial cells by charged particles.

Experimental studies have shown that high linear-energy transfer (LET) charged particles can be more effective than x-rays and gamma-rays in inducing oncogenic transformation in cultured cells and tumors in animals. Based on these results, experiments were designed and performed with an immortal human mammary epithelial cell line (H184B5), and several clones transformed by heavy ions were obtained. Cell fusion experiments were subsequently done, and results indicate that the transforming gene(s) is recessive. Chromosome analysis with fluorescence in situ hybridization (FISH) techniques also showed additional translocations in transformed human mammary epithelial cells. In addition, studies with these cell lines indicate that heavy ions can effectively induce deletion, break, and dicentrics. Deletion of tumor suppressor gene(s) and/or formation of translocation through DNA double strand breaks is a likely mechanism for the initiation of oncogenic transformation in human mammary epithelial cells.

Breast↗

Centric rings, acentric rings and excess acentric fragments based on a random-walk interphase chromosome model.

Excess acentric fragments, consisting of acentric rings and acentric linear fragments, are among the most frequent kinds of chromosome-type aberrations produced by radiation. The frequency of acentric rings cannot be obtained directly by experiment but is estimated here from the ratio of acentric to centric rings, evaluated using a random-walk model for the organization of chromatin during interphase and an assumption that the probability of an exchange formation is proportional to the rate of collision between two DSB. This ratio is calculated to be 2.5 in low-LET irradiated human fibroblasts, significantly greater than the ratio if proximity effects are not considered. The calculated frequency of acentric rings is insufficient to account for all the observed excess acentric fragments. Assuming that the rest of the excess acentric fragments are due to incomplete exchanges, all possible recombinations between two DSB that result in acentric rings and acentric linear fragments have been identified. From the chromosome aberration data, the incompleteness parameter has been estimated. Intra-arm chromosome exchanges, either complete or incomplete, were estimated to account for more than 50% of the excess acentric fragments in human fibroblasts.

Chromosome Aberrations↗

Cytogenetic effects of space radiation in lymphocytes of MIR-18 crews.

For assessing health risk, the measurement of physical dose received during a space mission, as well as the LETs, energies and charges of particles is important. It is also important to obtain quantitative information regarding the effectiveness of space radiation in causing damage to critical biological targets, e.g., chromosomes, since at present the estimated uncertainty of biological effects of space radiation is more than a factor of two. Such large uncertainty makes accurate health risk assessment very difficult. For this very reason, a study on cytogenetic effects of space radiation in human lymphocytes was proposed and done for MIR-18 mission. This study used FISH technique to score chromosomal translocations and C-banding method to determine dicentrics. Growth kinetics of cells and SCE were examined to ensure that chromosomal aberrations were scored in first mitosis and were induced not by chemical mutagens. Our results showed that chromosomal aberration frequency of post-flight samples was significantly higher than that of pre-flight ones and that SCE frequency was similar between pre- and post-flight samples. Based on a dose-response curve of preflight samples exposed to gamma rays, the absorbed dose received by crews during the mission was estimated to be about 14.5 cSv. Because the absorbed dose measured by physical dosimeters is 4.16 cGy for the entire mission, the RBE is about 3.5.

Chromosome Aberrations↗

Biodosimetry results from space flight Mir-18.

Astronauts are classified as radiation workers due to the presence of ionizing radiation in space. For the assessment of health risks, physical dosimetry has been indispensable. However, the change of the location of dosimeters on the crew members, the variation in dose rate with location inside the spacecraft and the unknown biological effects of microgravity can introduce significant uncertainties in estimating exposure. To circumvent such uncertainty, a study on the cytogenetic effects of space radiation in human lymphocytes was proposed and conducted for Mir-18, a 115-day mission. This study used fluorescence in situ hybridization (FISH) with whole-chromosome painting probes to score chromosomal exchanges and the Giemsa staining method to determine the frequency of dicentrics. The growth kinetics of cells and sister chromatid exchanges (SCEs) were examined to ensure that chromosomal aberrations were scored in the first mitosis and were induced primarily by space radiation. Our results showed that the frequency of chromosomal aberrations increased significantly in postflight samples compared to samples drawn prior to flight, and that the frequency of SCEs was similar for both pre- and postflight samples. Based on a dose-response curve for preflight samples exposed to gamma rays, the absorbed dose received by crew members during the mission was estimated to be about 14.75 cSv. Because the absorbed dose measured by physical dosimeters is 5.2 cGy for the entire mission, the RBE is about 2.8.

Astronauts↗

Biodosimetry of ionizing radiation by selective painting of prematurely condensed chromosomes in human lymphocytes.

Painting of interphase chromosomes can be useful for biodosimetric purposes in particular cases such as radiation therapy, accidental exposure to very high radiation doses and exposure to densely ionizing radiation, for example during space missions. Biodosimetry of charged-particle radiation is analyzed in the present paper. Target cells were human peripheral blood lymphocytes irradiated in vitro with gamma rays, protons and iron ions. After exposure, lymphocytes were incubated for different times to allow repair of radiation-induced damage and then fused to mitotic hamster cells to promote premature condensation in the interphase chromosomes. Chromosome spreads were then hybridized with whole-chromosome DNA probes labeled with fluorescent stains. Dose-response curves for the induction of chromatin fragments shortly after exposure, as well as the kinetics of rejoining and misrejoining, were not markedly dependent on linear energy transfer. However, after exposure to heavy ions, more aberrations were scored in the interphase cells after incubation for repair than in metaphase samples harvested at the first postirradiation mitosis. On the other hand, no significant differences were observed in the two samples after exposure to sparsely ionizing radiation. These results suggest that interphase chromosome painting can be a useful tool for biodosimetry of particle radiation.

Animals↗

Induction of chromosome aberrations in human cells by charged particles.

Chromosome aberrations induced by high-energy charged particles in normal human lymphocytes and human fibroblasts have been investigated. The charged particles included 250 MeV/nucleon protons, 290 MeV/nucleon carbon ions and 1 GeV/nucleon iron ions. The energies of the charged particles were higher than in most of the studies reported in the literature. Lymphocytes were stimulated to grow immediately after irradiation, while fibroblasts were incubated at 37 degrees C for 24 h for repair. Chromosomes were collected at the first mitosis after irradiation and chromosome aberrations were scored using the fluorescence in situ hybridization (FISH) technique with a whole-chromosome 4 probe. Chromosome aberrations were classified as reciprocal exchanges, incomplete exchanges, deletions and complex exchanges. The relative biological effectiveness (RBE) for each type of aberration was calculated by dividing a dose of 4 Gy by the dose of the charged particles producing the same effect as 4 Gy of gamma rays. Results of this study showed that complex aberrations have the highest RBE for radiation of high linear energy transfer (LET) for human lymphocytes, but for fibroblasts, the greatest effect was for incomplete exchanges. For both lymphocytes and fibroblasts, iron ions induced a similar fraction of aberrant cells.

Carbon↗