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Biomedical subjects

T T Lin

Publications and source records attributed to T T Lin.

At least 19 recordsLinked to original sources
PubMed2001

Axonal regeneration and functional recovery after complete spinal cord transection in rats by delayed treatment with transplants and neurotrophins.

Little axonal regeneration occurs after spinal cord injury in adult mammals. Regrowth of mature CNS axons can be induced, however, by altering the intrinsic capacity of the neurons for growth or by providing a permissive environment at the injury site. Fetal spinal cord transplants and neurotrophins were used to influence axonal regeneration in the adult rat after complete spinal cord transection at a midthoracic level. Transplants were placed into the lesion cavity either immediately after transection (acute injury) or after a 2-4 week delay (delayed or chronic transplants), and either vehicle or neurotrophic factors were administered exogenously via an implanted minipump. Host axons grew into the transplant in all groups. Surprisingly, regeneration from supraspinal pathways and recovery of motor function were dramatically increased when transplants and neurotrophins were delayed until 2-4 weeks after transection rather than applied acutely. Axonal growth back into the spinal cord below the lesion and transplants was seen only in the presence of neurotrophic factors. Furthermore, the restoration of anatomical connections across the injury site was associated with recovery of function with animals exhibiting plantar foot placement and weight-supported stepping. These findings suggest that the opportunity for intervention after spinal cord injury may be greater than originally envisioned and that CNS neurons with long-standing injuries can reinitiate growth, leading to improvement in motor function.

Animals↗
PubMed1999

Structures and cytotoxicity relationship of isoaaptamine and aaptamine derivatives.

A series of 9-O-acylisoaaptamine (3-14) and 4-N-acyl-dihydroaaptamine (16-19) derivatives have been prepared and evaluated for antitumor activity against murine P-388 and human tumor cells including KB16, A549, and HT-29 cell lines. All of compounds showed significant cytotoxicity against P-388 cells. Among them, compounds 9-11 showed potent activity as isoaaptamine (1). There was an apparent lack of linear relationship between cytotoxicity and carbon number of the side chain. The structure and activity relationship for these particular compounds are discussed.

Animals↗
PubMed1996

Role of interferon regulatory factor-1 in the induction of biliary glycoprotein (cell CAM-1) by interferon-gamma.

Biliary glycoprotein (BGP), also known as C-CAM-1, has been shown to be down-regulated in colon and prostate tumors. Previously, we demonstrated that BGP mRNA is up-regulated by interferon-gamma (IFN-gamma) in colon cancer cell lines (Takahashi, H., Okai, Y., Paxton, R. J., Hefta, L. J. F., and Shively, J. E. (1993) Cancer Res. 53, 1612-1619). We now show that the BGP promoter contains an interferon-sensitive response element (ISRE) that is specifically protected in in vivo footprints. Interferon regulatory factor-1 (IRF-1) was identified as the ISRE-binding factor by electrophoretic mobility shift assays. The induction of IRF-1 mRNA by IFN-gamma in HT-29 cells reaches a maximum at 6 h and is superinduced by cycloheximide. Four mRNA species for BGP are induced by IFN-gamma, the major band of which is inhibited by cycloheximide. Transfection of HT-29 cells with an IRF-1 expression plasmid (pAct-1) transactivates a BGP promoter reporter gene containing wild-type (but not mutant) ISRE. Electrophoretic mobility shift assay analysis of a second footprint reveals the binding of Sp1, an Sp1-like protein, and upstream stimulatory factor. The Sp1-like complex was also induced by IFN-gamma treatment of HT-29 cells and may be a second point of transcriptional control for the BGP gene.

Adenosine Triphosphatases↗
PubMed1996

Detection of Helicobacter pylori by polymerase chain reaction assay using gastric biopsy specimens taken for CLOtest.

The concordance rate between a rapid urease test (CLOtest) and polymerase chain reaction (PCR) assay for the detection of Helicobacter pylori in gastric biopsy samples was investigated. To avoid the bias produced by patchy distribution of the organism in the stomach, the samples used for these two tests were not obtained from two different sites of the antrum. Instead, the PCR assay was performed with the the same biopsy sample that was taken for the CLOtest. Among 82 biopsy samples included for this study, 56 were positive and 26 were negative by CLOtest. Of the 56 CLOtest-positive samples, 52 (93%) were also positive by PCR assay, and of the 26 CLOtest-negative samples, 20 (78%) were negative by PCR assay. The total concordance rate of these two tests was 87.6%. Of the 4 cases with CLOtest-positive and PCR-negative results, 3 had been treated with long-term H2 blockers. Of the 6 patients with CLOtest-negative and PCR-positive results, 4 suffered from recurrent or poorly healing duodenal ulcers. Interestingly, a significantly lower density of the PCR products was observed during electrophoresis analysis for all the 6 cases, presumably due to a small number of H. pylori in these samples. These results indicated that PCR might be used as a complementary assay for CLOtest. False negative results by CLOtest might occur when only a small amount of H. pylori was present in the samples, which could be detected by subsequent PCR assays using the same biopsy specimens. The clinical significance of such CLOtest-negative and PCR-positive cases requires further study.

Adult↗
PubMed1995

Detection and partial sequence analysis of Helicobacter pylori DNA in the bile samples.

The existence of Helicobacter pylori in the biliary tract was investigated. Seven bile samples were included in this study. Among them, six bile samples were collected by percutaneous transhepatic cholangiodrainage and the other by needle aspiration during cholecystectomy. Using nested PCR with two sets of primers homologous to the urease A gene, Helicobacter pylori DNA was detected. Three samples, one from a patient with advanced gastric cancer involving the pancreatic head and two from patients with pancreatic head tumor, were found to be positive for Helicobacter pylori DNA. On the other hand, three samples from patients with cholangiocarcinoma and one from a patient with chronic cholecystitis were all negative. To further verify the specificity of our PCR analysis, partial sequences of the PCR products from the three positive samples were analyzed by direct sequencing. Several silent mutations and a missense mutation (AAA to AGA; Lys-164 to Arg-164) were identified in the urease A gene. We conclude that Helicobacter pylori DNA can be easily detected in the bile samples. The possibility of asymptomatic cholangitis caused by this organism requires further investigation.

Adult↗
PubMed1993

Estramustine and estrone analogs rapidly and reversibly inhibit deoxyribonucleic acid synthesis and alter morphology in cultured human glioblastoma cells.

Estramustine is an estradiol-based agent that has been shown to accumulate in human glioma cells, resulting in a concentration-dependent alteration in cell size and shape within minutes and an inhibition of proliferation over 3 to 6 days. We evaluated human glioblastoma cultures with [3H]thymidine incorporation assays to determine estramustine's early effects on deoxyribonucleic acid synthesis in these tumors. Because estramustine shares a common structural motif with other antimicrotubule drugs, we synthesized four A-ring conjugates of estrone that contained a carbamate moiety but lacked nitrogen mustard. These analogs were examined by [3H]thymidine incorporation and compared with vinblastine. Greater than 70% inhibition of [3H]thymidine incorporation occurred within 1 hour of treatment with estramustine at 10(-5) mol/L, which increased to 80% inhibition at 4 hours. Ethyl carbamate JE208 was nearly as effective as estramustine in inhibiting deoxyribonucleic acid synthesis, and both were more effective than vinblastine. The inhibitory effects of estramustine and estrone analogs were reversible; vinblastine was not reversible. Although estramustine and JE208 induced similar antiproliferative and morphological changes in glioblastoma cells that persisted for at least 4 days, there was a modest recovery of morphology and thymidine incorporation with JE208 after prolonged treatment. The common findings with estramustine and JE208 suggest that these agents may have a similar mechanism of action and form the basis for the investigation of new agents that may rapidly and reversibly inhibit glioblastoma.

Brain Neoplasms↗
PubMed1991

Subfreezing volumetric behavior and stochastic modeling of intracellular ice formation in Drosophila melanogaster embryos.

Cryomicroscopic observations were made of the volumetric behavior and kinetics of intracellular ice formation (IIF) in Drosophila melanogaster embryos in a modified cell culture medium (BD.20) or BD.20 + 2 M ethylene glycol. After rapid cooling to a given temperature, transient volumetric contraction of the embryos during the isothermal period was quantified by computerized video image analysis. Fitting these data to the numerical solution of the volume flux equation yielded estimates of the hydraulic permeability coefficient (Lp) for individual embryos at various subfreezing temperatures. Lp approximately followed an Arrhenius relation between -2 and -9 degrees C, with a value of 0.168 microns/(min-atm) extrapolated to 0 degrees C and an apparent activation energy delta E of 38.9 kcal/mol. IIF during an isothermal period occurred at random times whose characteristic temperature range and kinetics were affected by the presence of ethylene glycol. A stochastic process model developed to fit these data indicated the influence of both time-dependent and instantaneous components of IIF, presumed to be the result of seeding and heterogeneous nucleation, respectively. The presence of 2 M ethylene glycol depressed the characteristic temperature of instantaneous IIF by about 12 degrees C and reduced the rate constant for time-dependent IIF. Comparison with observed incidences of IIF yielded an estimate of the supercooling tolerance of 3 to 5 degrees C.

Animals↗
PubMed1990

Cryopreservation of Drosophila melanogaster embryos.

There is an urgent need to preserve the ever-increasing number (greater than 30,000) of different genetic strains of D. melanogaster that are maintained in national and international stock centres and in the laboratories of individual investigators. In all cases, the stocks are maintained as adult populations and require transfer to fresh medium every two to four weeks. This is not only costly in terms of materials, labour and space, but unique strains are vulnerable to accidental loss, contamination, and changes in genotype that can occur during continuous culture through mutation, genetic drift or selection. Although cryopreservation of Drosophila germ-plasm would be an enormous advantage, many attempts using conventional procedures have been unsuccessful. D. melanogaster embryos are refractory to conventional cryopreservation procedures because of the contravening conditions required to minimize mortality resulting from both intracellular ice formation and chilling injury at subzero temperatures. To overcome these obstacles, we have developed a vitrification procedure that precludes intracellular ice formation so that the embryos can be cooled and warmed at ultra-rapid rates to minimize chilling injury, and have recovered viable embryos following storage in liquid nitrogen. In a series of 53 experiments, a total of 3,711 larvae emerged from 17,280 eggs that were cooled in liquid nitrogen (18.4 +/- 8.8%). Further, using a subset from this population, approximately 3% of the surviving larvae (24/800) developed into adults. These adults were fertile and produced an F1 generation.

Animals↗
PubMed1989

A two-step method for permeabilization of Drosophila eggs.

As a first step in developing a procedure for the cryopreservation of Drosophila melanogaster embryos, we have established a method for permeabilization of the eggcase and have initiated studies of the hydraulic conductivity of permeabilized embryos and the permeation of selected cryoprotective agents. The eggcase of D. melanogaster embryos has a wax layer that precludes any flux of water. A two-step procedure employing organic solvents was developed to effect removal of the wax layer with minimal deleterious effects on the embryos. Dechorionated embryos (Oregon-R strain P2, 12 to 13 hr old) were rinsed sequentially in isopropanol and hexane. After removal of solvent, embryos were held in a modified cell culture medium for further manipulation. This procedure routinely yielded 80 to 95% of the eggs permeabilized (as determined by osmotic contraction in 1 M sucrose) and 75 to 90% survival (incidence of hatching). Hydraulic conductivity of permeabilized embryos and permeation of cryoprotectants were determined using a microdiffusion chamber and computerized video microscopy. Regression analysis of the volumetric data from individual embryos yielded the Boyle-van't Hoff function FVeq = 0.124 (osm-1) + 0.541 with the standard deviations of slope and intercept (Vb) being 0.010 and 0.040, respectively. Permeabilized embryos exhibited ideal osmotic behavior over the range of 0.265 to 2.00 osm. The mean hydraulic conductivity coefficient (Lp) was 0.722 +/- 0.366 micron/(min.atm) at 20 degrees C, based on observations of contraction following a step change in concentration of Ringer's solution.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Propanol↗
PubMed1989

Osmometric behavior of Drosophila melanogaster embryos.

The osmometric behavior of Drosophila melanogaster embryos in permeabilized eggs was studied in a microscope diffusion chamber designed to impose a rapid change in osmotic environment at various temperatures. A numerical model of NaCl diffusion in the chamber predicted that radial variations in concentration arising from the presence of a thin film of solution at the top of the chamber were negligible. On the basis of transient electrical conductance measurements in the chamber, characteristic time constants for the change in concentration averaged over the chamber depth occupied by the eggs were 0.99, 0.77, and 0.60 min at 0, 10, and 20 degrees C, respectively. The chamber response was sufficiently rapid that the characteristic response of the embryo was not masked. Equilibrium volumetric behavior of the embryos indicated that they behaved as nearly ideal osmometers over the range of 0.256 to 2.000 osm, and followed the relation FVeq = 0.123C-1 + 0.541, where FVeq is equilibrium fractional volume and C is osmolality. Nonlinear regression of volumetric data during osmotic contraction yielded an average Lp of 0.722 micron/(min.atm) at 20 degrees C and an apparent activation energy delta E of 8.11 kcal/mol. The coefficients of variation in the Lp estimates among individual embryos were 38, 18, and 47% at 0, 10, and 20 degrees C, respectively. With the use of probability rules and a model for volumetric behavior during freezing, it was determined that the observed variability in Lp (assuming delta E is fixed) considerably broadens the transition range of cooling rates over which the predicted probability of intracellular ice formation goes from 0 to 1. However, experimental observations (21) show the actual transition range is even wider, indicating that there exist other important sources of variability which determine the event of ice formation in D. melanogaster embryos.

Animals↗
PubMed1987

[Clinical experience of tegafur-uracil (UFT) against bladder cancer and renal cell carcinoma].

The safety of prolonged administration of UFT in which tegafur and uracil were mixed in a ratio of 1:4 in molar fraction was studied in 44 cases of bladder cancer and 10 cases of renal cell carcinoma. Daily doses of UFT were 300-600 mg, and average total doses administered were 102.0 g for bladder cancer and 116.6 g for renal cell carcinoma cases. Incidence of adverse effects were 25.0% in bladder cancer and 18.5% in renal cell carcinoma cases. Anorexia, nausea, vomiting and decrease in WBC were observed, but rates of having discontinued the administration of UFT were very low, being 9.1% in bladder cancer and 10.0% in renal cell carcinoma. Thus, UFT was considered to be tolerable during prolonged use in bladder cancer and renal cell carcinoma and also a drug in which more usefulness is expected in multidisciplinary treatments in future.

Adult↗
PubMed1986

Detection of antibodies to HTLV-III by ELISA in AIDS risk groups in Taiwan: a preliminary report.

A total of 2321 serum samples were collected from a variety of AIDS risk groups. The samples were tested for anti-HTLV-III using ELISA. Low prevalences of seropositivity were detected in the high-risk groups. Among 120 homosexuals/bisexuals, one seropositive suffering from full-blown AIDS was an American traveler. Another native homosexual who yielded a high ELISA reading was a "possible" AIDS. Three hemophiliacs with strongly positive reactions received injections of a U.S.-produced factor VIII; all are asymptomatic currently. A patient with hairy cell leukemia had a markedly elevated ELISA reading. Another patient with syphilis also had a markedly high reading, despite having no other known risk factor. Among the low-risk groups a patient who had suffered from oral candidiasis for eight years had no risk factor, yet he yielded repeatedly high ELISA readings. Another patient with a weak positive reaction was a symptomless blood donor. This preliminary study concludes that Taiwan is several years behind the U.S. and is at present not an endemic area for AIDS. To achieve successful AIDS control in the future, however, the homosexuals in Taiwan should change their sexual behavior now. Since many initially weakly-reactive samples became negative on repeated testing it appears that non-specific or false positive ELISA reactions occur frequently. Accordingly when ELISA is used for diagnostic purposes, additional confirming tests are mandatory.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Progesterone receptor in the human uterine cervix.

A progesterone receptor (PR) in human uterine cervical nuclei was demonstrated by a nuclear exchange assay using a synthetic progestin, promegestone (R5020) as a radio-labeled ligand. Total exchange of previously bound progesterone with R5020 was achieved by incubation at 0 degree C for 3 h. A 0.6 M KCl solution was used to extract the nuclear PR in uterine cervical tissue, and the dextran coated charcoal (DCC) method was used to separate the free [3H] R5020 from the bound form. Scatchard plots of nuclear PR binding showed two components with dissociation constants of Kd = 2.3 X 10(-10) and 4.6 X 10(-9) M. Three histological regions of the uterine cervix was studied as to their nuclear PR contents throughout the menstrual cycle. In the follicular phase, the connective tissue (CT) had the highest PR concentration (658.9 fmole/mg DNA), followed by the columnar epithelium (CE) (253.6 fmole/mg DNA), and the squamous epithelium (SE) (184.7 fmole/mg DNA). In the luteal phase, there was no significant difference among the three regions. Comparing these phases of cycle revealed that the CT had higher PR contents in the follicular phase than in the luteal phase, but no such difference was found in the CE or SE. These three regions had the same Kd value in both phases.

Adult↗