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Biomedical subjects

T M Lin

Publications and source records attributed to T M Lin.

At least 19 recordsLinked to original sources

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

Interaction of factors associated with cancer of the nasopharynx.

A retrospective study of nasopharyngeal carcinoma (NPC) revealed that smoking, working under poor ventilation, use of nasal balms or oil for nasal and throat troubles, use of herbal drugs, and anti-EBV antibody titer were found statistically associated. The dural interactions of these factors to the risk of NPC were presented. Except in work conditions with poor ventilation and when herbal drugs are used, all the combinations were synergistic. The synergistic actions were especially remarkable with smoking and other factors. The possible etiological mechanisms of NPC are discussed.

Antibodies, Viral

Immunological relationships of human and subhuman primate pregnancy-associated plasma proteins.

(1) Four pregnancy-associated plasma proteins cross-reactive with antibodies to the human pregnancy proteins were detected in several species of pregnant subhuman primates. In the case of the two apes studied (chimpanzee and orangutan), these appeared to be immunologically identical to the human PAPPs (PAPP-A, -B, -C, and HCS). In the old world monkeys analyzed, equivalent partially cross-reactive PAPPs were found; while in the new world squirrel monkey, only faint traces of cross-reactive PAPP-C and HCS were observed with the most sensitive methods used. (2) As in the human, these proteins appeared to be specific for pregnancy, not being detectable in nonpregnant animals, female or male. (3) The pregnant chimpanzee possessed significantly higher concentrations of PAPP-A and PAPP-C than did women at an equivalent stage of pregnancy, while the HCS and PAPP-B levels appeared to be approximately the same. (4) The primate PAPP-C analogues were more complex than human PAPP-C, often revealing multiple gel diffusion patterns with subfractions of differing electrophoretic mobilities. (5) Based on the changes of electrophoretic mobility upon exposure to neuraminidase, the subhuman primate as well as human PAPP-A and PAPP-C appeared to be glycoproteins containing sialic acid. (6) In the chimpanzee and rhesus monkey, as in the human, the levels of PAPP-A, PAPP-C, and HCS were appreciably higher during the third trimester of pregnancy than they were during the second trimester.

Animals

Pregnancy-associated plasma proteins in pregnant and pseudopregnant rats.

As in the human, the rat pregnancy-associated plasma proteins consisted of four distinct entities as revealed by immunological methods. All showed gradual increases during gestation and rapid disappearance postpartum. They could be physicochemically, although not immunologically, tentatively related to the human pregnancy proteins. None of them was detectable in the serum of rats at various stages of pseudopregnancy, nor in nonpregnant rats.

Animals

Characterization and purification of pregnancy-associated plasma protein B (PAPP-B).

PAPP-B is a pregnancy-specific beta 1-glycoprotein of large molecular weight, about 1,000,000 as determined by Sepharose 4B and 6B gel filtration. Its isoelectric point is between pH 4.6 and 5.0. It has been purified at least 800-fold from term pregnancy serum by a sequence of steps involving salting out at 30% saturation with ammonium sulfate (1,2M), DEAE-cellulose chromatography, Sepharose 4B gel filtration and hydroxylapatite chromatography. Monospecific antiserum to PAPP-B has been prepared, and used to differentiate it from several other newly reported tumor or pregnancy proteins. PAPP-B was found to increase slowly during the second trimester of pregnancy and more steeply during the third, reaching a plateau in late gestation. During the postpartum period, PAPP-B disappeared quite rapidly, with an apparent half-life of less than 1 day.

Blood Proteins

Plasma concentrations of four pregnancy proteins in complications of pregnancy.

Toxemia of pregnancy was associated with an elevation of the pregnancy-associated plasma protein (PAPP)-A concentration, as compared to the level in normal pregnancy in the last month of gestation. The other pregnancy proteins measured were not altered in toxemia. In twin pregnancies, the PAPP-A, PAPP-C, and human placental lactogen levels were all increased, particularly PAPP-A. On the other hand, pregnancy zone protein was not affected by twinning. Pregnancy with diabetes showed normal levels of these proteins.

Blood Proteins

Antibodies to Epstein-Barr virus capsid antigen and early antigen in nasopharyngeal carcinoma and comparison groups.

Antibodies to Epstein-Barr virus capsid antigen (anti-VCA) and early antigen (anti-EA) were measured in 263 patients with nasopharyngeal carcinoma (NPC), 624 age- and sex-matched neighborhood controls, 570 family members of NPC patients and 830 family members of neighborhood controls in Taiwan. The distribution of antibody titers was significantly different between NPC patients and the other three groups. More than 55% and 45% of NPC patients had titers of greater than or equal to 1:640 and greater than or equal to 1:80 for anti-VCA and anti-EA, respectively, while less than 6.7% and 2.5% of the other three groups had such high titers. The geometric means of anti-VCA and anti-EA titers were 1:352 and 1:45, respectively, in NPC patients compared to less than 1:77 and 1:12, respectively, in the comparison groups. Anti-VCA and anti-EA titers were significantly correlated. The association of EBV with NPC is discussed.

Antibodies, Viral

Bovine pancreatic peptide: action on gastric and pancreatic secretion in dogs.

Bovine pancreatic peptide (BPP) is a straight chain peptide containing 36 amino acid residues that has recently been isolated from pancreatic tissue. At a dose of 40 mug/kg-h intravenously, it stimulated gastric acid secretion when given alone but inhibited the submaximal secretion induced by the C-terminal pentapeptide of gastrin. Basal pancreatic secretion of dogs was inhibited by BPP (1-10 mug/kg-h) inhibited pancreatic protein secretion but often showed a biphasic action on water-bicarbonate response, an initial augmentation followed by reduction. BPP (2-5 mug/kg-h) inhibited pancreatic water-bicarbonate and protein secretions induced by an infusion of secretin plus cholecystokinin. Des-tyrosyl-NH2 BPP lacking the C-terminal tyrosyl amide, failed to inhibit gastric acid induced by C-terminal pentapeptide of gastrin or pancreatic secretion induced by secretin. BPP had no hyper- or hypoglycemic, hyperkalemic, or diuretic actions in the dog.

Animals

Action of glucagon and aspirin on ionic flux, mucosal blood flow and bleeding in the fundic pouch of dogs.

Into vagally denervated (Heidenhain) pouches of 4 dogs 25 ml of 0.1 M HCl was instilled and removed at 30 min intervals for 6 hours. During the 4th, 5th, and 6th 30 min periods the acid instillate contained 5 mg/ml of aspirin. Aspirin significantly increased gastric-mucosal clearance of aminopyrine (mucosal blood flow), outputs of Na+, Ca++, Mg++, hemoglobin, and plasma transferrin-Cr51 into the pouch contents, and disappearance of H+ from lumen to mucosa. Glucagon, 50 mug/kg subcutaneously was given during irrigation with aspirin and again 1 hour later. Glucagon did not significantly affect loss of acid from lumen to mucosa or the increase in Na+, K+, Ca++, and Mg++ effluxes caused by aspirin. Glucagon significantly decreased mucosal blood flow and the hemorrhage and loss of plasma protein into the instillate induced by aspirin.

Aminopyrine