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Biomedical subjects

T M Lin

Publications and source records attributed to T M Lin.

At least 55 records · Page 3Linked to original sources

Dynamics of tumor cell clonogen repopulation in a murine sarcoma treated with cyclophosphamide.

Experiments were performed to establish the extent and kinetics of tumor cell repopulation in a murine sarcoma, designated SA-NH, treated with cyclophosphamide (CY). Mice bearing 8-mm leg tumors were treated with 200 mg/kg CY which caused a transient tumor regression. Changes in the absolute clonogen content of tumors was determined by the change in TCD50 values (50% tumor control) obtained under hypoxic conditions of local tumor irradiation at different times after CY treatment until tumors regrew to the pretreatment size. For comparison, hypoxic TCD50 values were determined during the growth of tumors not treated with CY. CY greatly depleted tumors of clonogenic cells as manifested by the reduction in the control TCD50 value of 64.5 Gy to 32.8 Gy 1 day after CY treatment. The reduced TCD50 value remained unchanged for 2 weeks after treatment with CY, at which time the TCD50 began to rapidly increase, continuing until the end of the observation period of 21 days when tumors reached the pretreatment size. In contrast, there was a constant but slower increase in TCD50 values during the growth of tumors not treated with CY. The daily increase in TCD50 was more than twice as high in CY-treated than in CY-untreated tumors: 4.5 Gy/day versus 2.1 Gy/day. This implies that the rate of clonogen production in CY-treated tumors was twice as high as that of unperturbed tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Carrier screening and prenatal diagnosis for alpha-thalassemia with biphasic polymerase chain reaction.

Alpha-thalassemia is the most common single gene disorder in Taiwan and Southeast China. The majority of alpha-thalassemic mutations in this area are alpha-thalassemia 1. Homozygous alpha-thalassemia 1 has been recognized as the most important cause of hydrops fetalis. To investigate the incidence of alpha-thalassemia 1 mutations and to characterize its molecular defects, cord blood electrophoresis was performed on 2,000 newborns, of which 99 (5%) cases were found to have hemoglobin (Hb) Bart's levels > 3.0%. A methodology using biphasic polymerase chain reaction (PCR) with nesting primers was developed to characterize the alpha-thalassemia 1 Southeast Asia type (SEA) deletion in the cases with detectable Hb Bart's levels. The SEA deletion was found in 92 (93%) of 99 cases. Prenatal screening was performed on couples with abnormal hematologic indices, and PCR was used to detect couples heterozygous for SEA deletion. Prenatal diagnosis was performed in 21 cases, and four cases were found to have a homozygous SEA deletion. This strategy can be applied to couples who need prenatal genetic counseling for alpha-thalassemia major in this area.

Asia, Southeastern↗

The binding of plasminogen fragments to cultured human umbilical vein endothelial cells.

Glu-plasminogen, kringle 1-5, kringle 1-3, and miniplasminogen exhibited strong binding to human umbilical vein endothelial cells (HUVEC). On the other hand, no significant binding was obtained with microplasminogen and kringle 4. Kringle 1-5 and miniplasminogen, which both contained kringle 5, specifically inhibited the binding of plasminogen to HUVEC while kringle 1-3 did not. The results implied plasminogen molecule contained at least two binding sites, with which it interacted HUVEC. The stronger binding site was located in kringle 5 and the weaker one was in kringle 1-3. Kringle 4 and the active site domain exhibited no significant binding to HUVEC. The interaction of plasminogen with HUVEC is mainly through binding site on kringle 5.

Amino Acid Sequence↗

Neonatal screening for alpha-thalassemia in southern Taiwan.

Screening peripheral or cord blood from newborn infants has been used for early detection of alpha-thalassemia conditions. The level of hemoglobin Bart's (Hb Bart's) in the blood correlates with the degree of alpha-gene deletion. Hence, the degree of gene deletion in an alpha-thalassemia carrier state can be estimated. Two thousand cord blood samples collected from the Tainan area were screened with cellulose acetate membrane electrophoresis for Hb Bart's. Ninety-nine of the 2,000 samples (4.95%) were positive for Hb Bart's. Concentrations of Hb Bart's varied from 3.2% to 30.7%. Of the 99 cases with Hb Bart's, 22 had Hb Bart's levels of 3.0% to 9.9%; 54 had Hb Bart's levels of 10.0% to 19.9%; and 23 had Hb Bart's levels of 20% to 40%. Routine cord blood screening by hemoglobin electrophoresis is recommended.

Fetal Blood↗

Use of flagellin-enriched antigens in a rapid, simple and specific quantitative enzyme immunoassay for Lyme disease antibodies in human serum samples.

An enzyme immunoassay (EIA, ELISA) using microwells coated with a flagellin-enriched fraction of B. burgdorferi and absorbent-containing sample diluent for the quantitative determination of Lyme disease (LD) IgG and IgM antibodies in human serum samples was described. This LD EIA required three 15-minute incubations at room temperature, followed by a 1-step normalization of photometer readings to EIA units (EU/ml). Compared with tests using the whole bacterial extract as antigens and a sample diluent containing 6% BSA, this new LD EIA revealed lower values for 20 syphilis (SS) and 21 normal serum samples (NS) but about the same for 21 Lyme disease (LD) samples, allowing lower cut-off points which would place almost all these SS and NS samples below while almost all LD samples above the positive cut-off point. The LD EIA results of larger numbers (67 to 291) of mixed samples correlated with results of four reference EIA. However, the LD EIA gave lower (2 to 4 fold) reactivities (index values) with SS and NS samples but higher values with positive serum samples than reference EIA. Thus, this LD EIA showed improvements in both specificity and sensitivity over other tests compared.

Adjuvants, Immunologic↗

Biological effects of sex hormone-binding globulin on androgen-induced proliferation and androgen metabolism in LNCaP prostate cells.

The effects of purified human sex hormone-binding globulin (SHBG) on androgen-sensitive cell proliferation were examined using a human prostatic cell line (LNCaP-FGC). Cells were grown for 5 days in medium supplemented with 10% charcoal-dextran-stripped human serum (10% CDHuS) and various concentrations of 5 alpha-dihydrotestosterone (DHT). In 10% CDHuS, without SHBG, the proliferative response of these cells to androgens was typically biphasic. At low androgen concentrations, cell yields were increased in a dose-dependent manner, reaching maximal levels at 0.3 nM DHT. However, at high androgen concentrations, cell proliferation was inhibited. Addition of purified human SHBG to the medium reduced the effectiveness of DHT on both phases of the proliferative response in a dose-dependent manner. These effects of SHBG appeared to be due primarily to the high affinity binding of DHT by SHBG. Proliferative responses induced by the synthetic androgen methyltrienolone (R1881), which binds poorly to SHBG, were not affected by added SHBG. Furthermore, analysis of the protein binding of DHT revealed that cell proliferation correlated best with the concentration of DHT not bound to SHBG. The presence of SHBG in the medium also altered the uptake and metabolism of DHT. LNCaP-FGC cells rapidly metabolized DHT to a polar glucuronidase-sensitive conjugate of DHT. In 10% CDHuS, LNCaP-FGC cells conjugated virtually all of the added DHT during the 5-day experiment. However, in medium containing SHBG, the SHBG-bound DHT remained unconjugated; more than 90% of the DHT initially bound to SHBG was present in the medium at the end of the experiment as unconjugated DHT. Uptake of radiolabeled DHT by cells was also inhibited by SHBG. In summary, these experiments provide evidence that 1) SHBG-bound DHT is not a signal for DHT-induced cell proliferation and 2) SHBG inhibits the uptake and metabolism of DHT by LNCaP-FGC cells.

Cell Division↗

Effects of hepatitis B virus, alcohol drinking, cigarette smoking and familial tendency on hepatocellular carcinoma.

Independent and interactive effects related to the development of hepatocellular carcinoma were assessed using a community-based case-control study for hepatitis B virus, habitual alcohol drinking, cigarette smoking, peanut consumption and history of hepatocellular carcinoma among the immediate family. All 200 male newly diagnosed hepatocellular carcinoma patients were recruited consecutively through the period of study as the case group from two teaching medical centers in northern and southern Taiwan. Healthy community residents matched one-to-one with cases on age, sex, ethnic group and residential area were selected as the control group. The carrier status of HBsAg and HBeAg was determined by blind radioimmunoassays, and other risk factors were obtained through standardized interviews according to a structured questionnaire. Conditional logistic regression analysis showed a significant association between hepatocellular carcinoma and the carrier status of HBsAg and HBeAg with an odds ratio of 16.7 and 56.5, respectively, for carriers of HBsAg alone and for carriers of both HBsAg and HBeAg. There was a dose-response relationship between cigarette smoking and hepatocellular carcinoma with an odds ratio of 1.1, 1.5 and 2.6, respectively, for those who smoked 1 to 10, 11 to 20 and more than 20 cigarettes a day. A significant association with hepatocellular carcinoma was also observed for the habitual alcohol consumer with an odds ratio of 3.4. Those whose immediate family had a history of hepatocellular carcinoma were more likely to have the disease develop, with an odds ratio of 4.6. However, the frequency of peanut consumption was not significantly associated with hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Endocrine effects of a new histamine H2-receptor antagonist, nizatidine (LY139037), in the male rat.

A new orally active histamine H2-receptor antagonist, nizatidine (LY139037), was evaluated in male rats for effects on mechanisms regulating accessory sex organ growth and function. Cimetidine antagonized androgen binding to cytosolic receptors in vitro while nizatidine had no effect. Nizatidine and cimetidine were administered at the ED50, 5 X ED50, or 10 X ED50 doses for inhibition of gastric acid secretion previously determined using in vivo dog and rat models. The relative potencies of both agents to antagonize histamine H2-receptor-mediated gastric acid secretory responses have been confirmed in human clinical trials. Neither nizatidine nor cimetidine antagonized the in vivo uptake or nuclear translocation of radiolabeled androgen into the hypothalamic-preoptic-amygdala, pituitary, or ventral prostate. Nizatidine, given at doses equal to and 10 X the ED50 gastric acid secretion inhibitory values, and cimetidine (10 X ED50 value) had no effect on the response of male accessory sex organs to a submaximally stimulating dose of androgen in castrated rats. High doses of dietary nizatidine (greater than 500 mg/kg-day) administered for 6 months did not alter intact rat male accessory sex organ weights or circulating androgen levels relative to untreated controls. Acute administration of either nizatidine or cimetidine produced transient elevations in plasma prolactin (PRL) levels. Cimetidine was more potent and consistent than nizatidine in producing these increases in circulating PRL. The data described herein support the contention that unlike cimetidine, nizatidine is not a pharmacological antagonist of androgen action and has less of a stimulatory effect upon plasma prolactin. Taken together, these studies indicate that in the male rat, nizatidine exhibits a large therapeutic index between its gastric antisecretory activity and potential endocrinological effects.

Androgens↗

[Radiotherapy of invasive thymoma--an experience of Veterans General Hospital-Taipei (1980-1987)].

Forty four patients with the diagnosis of invasive thymoma were reviewed. The male to female ratio was 1.44:1, and the median age was 42. Thirty nine percent of the patients were associated with myasthenia gravis. Surgical management involved a complete resection in 28 cases and thoracotomy with biopsy or partial resection in 13 cases. All patients received radiotherapy. The 5-year actuarial survival was 57%. Myasthenia gravis did not adversely affect the survival. The patients who underwent complete resection had better survival than those who had residual tumor before radiotherapy (5-year actuarial survival 75% vs 33%). Five cases developed recurrence outside the radiation treatment field. In order to avoid marginal recurrence after radiotherapy, we recommended low dose irradiation (1500-2000 cGy) to the involved hemithorax, followed by a boost to the primary site up to a total dose of 5000 cGy. For the patients who had gross disseminated disease in the pleural cavity, combination of chemotherapy and radiotherapy should be considered.

Adolescent↗

Two rapid and simple enzyme immunoassays for human antibodies to Entamoeba histolytica.

Two rapid and simple enzyme immunoassays (EIA) for antibodies to E. histolytica the protozoa causing ambiasis, are described. In the rapid dot EIA, a qualitative procedure, antigens were dried as a small dot (3 mm in diameter) on a thin white opaque polystyrene strip and serum samples were assayed undiluted. The assay required 3 incubation periods, 1 to 3 minutes each, and was completed in 9 minutes, with a positive reaction revealed as a blue color (precipitate) on the antigen dot and negative as colorless. The developed color is stable for permanent record. In the Microwell EIA, a quantitative procedure, antigens were dried in the Microwells. The assay also consisted 3 incubation periods of 15 minutes each, and was completed in 50 minutes. The results in absorbance values were normalized to EIA units (EU). Both tests had good reproducibility, sensitivity and specificity; and highly correlated with 3 other serologic tests. Their reagents can be stored for more than a year. Both tests could be suitable for small and physicians' office laboratories, especially in developing countries.

Animals↗

Sustained-release theophylline-uniphyllin in nocturnal asthmatics.

For a period of six months, we collected 12 cases of nocturnal asthmatics (7 males, 5 females); their ages ranged from 20 to 66 (the average age is 49). We found that administration of Uniphyllin (10 mg/kg) once a day at 6 PM could maintain the blood level of theophylline within therapeutic range at least 12 to 24 hrs. The peak expiratory flow rate of the 6 cases we collected, were significantly improved. The result of pharmokinetic parameters: 1) The average of a single dose (12 cases) is AUC (ug. hr/ml) 275.1 +/- 62. k; Kel (hr-1) 0.068 +/- 0.019; Ka (hr-1) 0.33 +/- 0.07); Tmax (hr) 6.3 +/- 1.4; T 1/2 (hr) 11.2 +/- 4.4; Clearance/F (ml/kg/hr) 37.9 +/- 9.0.2). The average of steady state (12 cases) is Css (mg/L) 5. 7 +/- 2.6; Cmax-Cmin (mg/L) 10.09 +/- 1.46.3). The average of relative bioavailability (3 cases) is 82%, 83%, 102%. However, the extent of absorption data is available for only 3 subjects. There are too few subjects to draw any meaningful conclusions about this relative bioavailability. Four cases show slight symptoms, including 1 case of dizziness, 2 cases of nausea, and 1 case gaseousness. It is suggested that the drug be administered at about 6-8 PM to coincide peak levels in the early morning in nocturnal asthmatics.

Adult↗

[Prediction of postoperative pulmonary function in the patient undergoing pneumonectomy using combined pulmonary function test and ventilation/perfusion scintiphotography].

A method to predict postoperative lung function following pneumonectomy has been used in 11 patients. Preoperative unilateral lung function can be predicted by combining the preoperative information on lung volumes obtained by spirometry with the distributional information obtained from ventilation and perfusion scintigrams in order to estimate lung function after pneumonectomy. There was a high degree of correlation between predicted and measured lung function for both FEV1 (r = 0.81, p less than 0.050, and FVC (r = 0.81, p less than 0.05). The postoperative FEV1 and FVC were within 200 ml of the predicted value in most of the patients. A more accurate and easy prediction of postoperative lung function is obtained using unilateral perfusion rather than ventilation scintigrams. We suggest that the combined the results of simple spirometric data and a quantitative right-vs-left perfusion lung scan using radioactive Tc-99m provides a simple non-invasive and accurate method for the pre-operative functional evaluation of the high risk patient.

Adult↗

A case-control study of primary hepatocellular carcinoma in Taiwan.

A case-control study was carried out to explore possible risk factors of primary hepatocellular carcinoma (PHC) in Taiwan. One hundred thirty-one PHC patients and 207 hospital control patients were interviewed and blood samples were collected for blood type and hepatitis B virus (HBV) infection marker tests. Eighty-three percent of the PHC patients were found to be hepatitis B surface antigen (HBsAg) positive as compared with 21.0% of the control patients with an odds ratio (OR) of 21.5. Hepatitis B e antigen (HBeAg) positive status increased the risk of PHC. No significant association was observed between erythrocyte genetic markers and PHC, except c of the Rh system, which was significantly lower in the PHC cases. As compared with the control patients, the PHC patients had a higher proportion with a history of liver diseases and more siblings affected with liver diseases. However, the variables such as cigarette smoking, alcohol drinking, peanut consumption, frequent intake of raw fish, heart diseases, peptic ulcer, malaria, hypertension, diabetes, color blindness, G-6-PD deficiency, surgical operation, blood transfusion, and liver diseases of parents and children were not found to be associated with PHC.

Adult↗