PubMed Health⌕ Search

Biomedical subjects

H M Lin

Publications and source records attributed to H M Lin.

At least 55 records · Page 3Linked to original sources
PubMed1998

Novel delivery systems for coagulation proteins.

Long-term haemophilia prophylaxis with clotting factors administered by alternative delivery modes requires stable liquid formulations of these factors. We developed an aqueous-formulated human coagulation factor IX (hCFIX) with in vitro half-life (T 1/2) of 6 weeks at 37 degrees C and 18 months at 4 degrees C. Upon bolus subcutaneous (s.c.) injection in animals, hCFIX had a bioavailability of up to 16% compared to intravenous (i.v.) dose. When delivered by s.c. implanted pumps, hCFIX attained > 2% of normal human levels in the animal plasma. Hydrogels of hCFIX in a chitosan derivative, N,O-carboxymethyl chitosan (NOCC), released hCFIX slowly in vitro, and when injected s.c., gave prolonged plasma levels over those obtained by bolus i.v. or s.c. injection. Freeze-dried human coagulation factor VIII (hCFVIII) formulated in non-aqueous solvents had in vitro T 1/2 up to 80 days at 37 degrees C.

Administration, Cutaneous↗
PubMed1998

Elements regulating differential activity of chicken histone H1 gene promoters.

The chicken genome contains six closely related histone H1 genes, each of which encodes a different H1 protein. The four common regulatory elements previously identified in H1 histone promoters are very similar in sequence and location in all chicken H1 genes, which gives rise to the question of how the six H1 variants are expressed at significantly different levels. Transient transfections of reporter gene transcriptional fusions indicate that approximately 200 bp of each promoter is sufficient to generate the observed spectrum of H1 promoter activity. The differences in H1 promoter-driven expression are shown to be explained by the relative activity of the previously characterized G box region and that of a novel element found between CCAAT and TATA that we have termed differential upstream sequence (Dus). Gel shift analysis indicated that the primary nuclear binding protein to the G box is one or more avian homologues of the Sp1 transcription factor. The Dus region binds multiple nuclear proteins, one of which is the recently described IBR/IBF factor. The differential affinities of the G box and Dus sequences of the H1 promoters for their respective nuclear binding factors correlate well with their relative promoter activities.

Animals↗
PubMed1997

Synthesis and cytotoxic evaluation of substituted sulfonyl-N-hydroxyguanidine derivatives as potential antitumor agents.

A series of sulfonyl-N-hydroxyguanidine derivatives was designed and synthesized for cytotoxic evaluation as potential anticancer agents on the basis of the lead compound LY-181984. Replacement of the ureido moiety of the lead compound with hydroxyguanidine provided a stable cytotoxic agent. The conformation of sulfonyl-N-hydroxyguanidine derivatives, such as N-(4-chlorophenyl)-N'-[(benzo[2,1,3]thiadiazol-4-yl)sulfonyl]-N"- hydroxyguanidine (4g), investigated utilizing HMBC NMR, theoretical calculations, and X-ray crystallography, indicated stacking of the two aromatic rings. The derivatives were evaluated for in vitro cytoxicity against five human tumor cell lines, including HepG2, TSGH 8302, COLO 205, KB, and MOLT-4. The cytotoxic activities of the derived compounds against the human tumor cell lines were equal to or greater than that of the lead compound. N-(4-Chlorophenyl)-N'-[[3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl]- N"- hydroxyguanidine (4n) and N-(4-chlorophenyl)-N'-[[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl] sulfonyl]-N"-hydroxyguanidine (4o) exhibited the greatest growth inhibition of solid tumor cell lines. Compound 4o was found to possess antitumor activity against murine K1735/M2 melanoma xenografts.

Animals↗
PubMed1997

Adjusting for regression toward the mean when variables are normally distributed.

Many studies use the same variable, for example blood pressure in studies of antihypertensive treatments, to identify subjects to be included in the study and to evaluate the effects of a treatment. As a consequence, if not properly accounted for, the effect of regression toward the mean can confound the evaluation of treatment effects if the study has no randomized control group. In this paper we review the methods that have been proposed for adjusting for the effect of regression toward the mean when the variable of interest is assumed to be normally distributed. Maximum likelihood estimation and moment-based estimation are considered, including more recent methods which can be applied when repeated measurements on each subject are available.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Assessing the effects of interventions using longitudinal data with samples subject to selection.

Consider an uncontrolled study in which subjects are selected to start a new intervention because one or more previous measurements of a variable are within a particular range. Our aim is to use the repeated values obtained prior and subsequent to the start of the intervention to assess the effects of its introduction. However, because selection is based on the same variable as is being used to assess efficacy, regression to the mean will confound the interpretation of the results. In this paper, we present a likelihood-based method for evaluating the effects of the intervention using the repeated measurements while adjusting for the effects of the selection. The method uses a linear model to describe each subject's pattern of responses before and after the start of the new intervention. Additionally, it assumes that the effect of starting the new intervention on an individual's intercept and slope is the same for all subjects. However, no distributional assumption is made about the pattern of the linear model across subjects, thus making it particularly appropriate for phase I/II studies when patient histories on those not selected for the study are not available.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Analysis of uncontrolled treatment changes in HIV clinical trails.

Some clinical trials involving subjects with the human immunodeficiency virus (HIV) allow a subject to change treatment when a marker of disease progression, for example, the CD4 cell count, falls below a defined threshold. Although the change does not involve a randomized control, there is considerable interest in assessing whether it might have beneficial effects on the marker levels. However, the effects of regression to the mean will confound a simple analysis of the repeated measurements obtained before and after the cross-over. In this paper, we present a likelihood-based methodology for this problem and apply it to assess a cross-over from placebo to treatment with a drug, zidovudine, in a cohort of HIV infected individuals. This cross-over occurred when a subject first had two successive CD4 cell counts below 500/mm3. As well as providing important information about the effects of introducing zidovudine among subjects with early asymptomatic HIV infection, this paper illustrates methods for verifying model assumptions, an important component of such analyses which are necessarily model dependent.

Adolescent↗
PubMed1996

Influence of HLA matching on thoracic transplant outcomes. An analysis from the UNOS/ISHLT Thoracic Registry.

BACKGROUND: The benefit of matching donor organs and recipients for HLAs has been well established in renal transplantation and has been suggested for thoracic organ transplantation. To determine the effect of HLA matching in cardiac and single-lung transplantation, the following study was performed. METHODS AND RESULTS: Using the joint Thoracic Transplant Registry or the United Network for Organ Sharing and the International Society for Heart and Lung Transplantation, all adult primary heart and single-lung transplant procedures performed in the United States from October 1987 through December 1993 were analyzed to determine the effects of HLA matching on transplant mortality. Both total HLA matches and matches at individual HLA loci were considered. Including HLA matching, 16 potential risk factors for heart transplant outcome and 16 potential risk factors for lung transplant outcome were subjected to multivariate analysis. A total of 10752 heart transplants and 1239 lung transplants were included in the independent analyses for each organ. For heart transplantation, there was a progressive reduction in risk for greater matching (1 or 2 matches: risk ratio, 0.83; 3 matches: risk ratio, 0.67; 4 to 6 matches: risk ratio, 0.59; all P < or = .01). The primary benefit of matching appeared to be at the A and DR loci (risk ratios, 0.87 and 0.79, respectively; P < .001). For lung transplantation, any matching had an independent positive effect on outcome; however, the relationship between numbers of HLA matches and relative risk was not present and ranged from risk ratios of 0.71 to 0.87 (P = .01 and P = .47, respectively). In this analysis, only matching at the A locus appeared to statistically influence outcome (risk ratio, 0.76; P = .01). CONCLUSIONS: These data demonstrate that HLA matching independently impacts survival in both heart and single-lung transplantation.

Adult↗
PubMed1996

Suppression of the tumorigenicity of human hepatoma hep3B cells by long-term retinoic acid treatment.

We cultured human hepatoma Hep3B cells in the presence of RA (10(-5) M) for 30 days; the expression of both alpha-fetoprotein and hepatitis B virus surface antigen were suppressed over 70% at the transcriptional level by RA treatment. The doubling time of RA treated Hep3B cells was slightly different from the control cells when they were cultured in 5% fetal calf serum/DMEM medium. However, cultured under serum-free conditions, the control Hep3B cells still grow, but the RA treated cells could not attach to the substratum of the culture plate and stopped growing. In vivo assay indicated that RA treatment completely suppressed the tumorigenicity of Hep3B cells in nude mice.

Animals↗
PubMed1995

Clinical use of pentastarch in cardiac surgery without homologous blood transfusion.

In an attempt to avoid the use of homologous blood transfusion, we used pentastarch 6% or 10% in a consecutive series of open heart surgery. After induction of anesthesia, whole blood 500 cc was withdrawn from the patient via an artery line, and 6% or 10% pentastarch 500 cc was infused simultaneously via a central venous line. A further 500 cc pentastarch was placed in the heart-lung machine as a priming solution. After the operation the autologous blood was transfused. Pentastarch 500cc was also infused in the intensive care unit as a plasma expander. Significant improvements in cardiac output with decrease in hematocrit, plasma viscosity, systemic and pulmonary vascular resistance were noted after pentastarch infusion, due to its hemodiluting effects. Patients treated with pentastarch did not require transfusion of homologous blood, and they also displayed no abnormal coagulopathy, or increased amounts of postoperative bleeding during hospitalization. All patients were discharged without additional hospital stay. With the aid of pentastarch, acute normovolemic hemodilution can be performed safely in cardiac surgery with the advantages of saving stored blood, reducing the risks associated with homologous blood transfusion and profiting from hemodilution. It is therefore concluded that cardiac surgery can be performed safely with 6% or 10% pentastarch without any homologous blood transfusion.

Adult↗
PubMed1995

Use of historical marker data for assessing treatment effects in phase I/II trials when subject selection is determined by baseline marker level.

Although the primary focus of Phase I clinical trials is to assess clinical pharmacology and possible toxicities, any information on the potential effect of treatment would be useful in helping to determine priorities between treatments for further study. We consider the scenario where data are routinely collected on a marker of disease progression on all patients attending a clinic, but the trial is restricted to patients who have a marker level within a defined range at study baseline. Using a two-step approach to estimation, the marker histories are used to give predictions of marker values during trial follow up, assuming no treatment effect and adjusted for the regression to the mean effect, for those subjects selected for the trial. Comparison between the observed responses and the predicted values then forms the basis for moment-based estimation and hypothesis testing for the treatment effect. The method is easily extended to compare summary measures for repeated measurements during follow up in the trial to predicted summary measures. An example using CD4 cell counts in an AIDS study is given.

Biometry↗
PubMed1994

Localization of H(+)-ATPase and carbonic anhydrase II in ameloblasts at maturation.

The localization of vacuolar-type H(+)-ATPase and carbonic anhydrase II (CA II) in rat incisor enamel organs at maturation was examined by light and electron microscopy. The immunoreactivity for both vacuolar-type H(+)-ATPase and CA II was intense on the ruffled border of ruffle-ended ameloblasts (RA), but moderate at the distal end of smooth-ended ameloblasts (SA). Immuno-gold particles indicated that CA II was not confined to the ruffled border of RA alone, but also distributed in the cytoplasm of RA and SA. These findings suggest that RA may secrete protons produced by CA II via the ruffled border into enamel by active transport of vacuolar-type H(+)-ATPase. Secreted protons may activate hydrolytic enzymes to degrade the organic components of enamel matrix. Vacuolar-type H(+)-ATPase on vesicles of SA suggests that a specific configuration of ruffled borders in RA may be formed by the fusion of vesicle membranes in the distal end of cytoplasm of SA.

Ameloblasts↗
PubMed1993

An experimental method for determining the Hildebrand solubility parameter of organic nonelectrolytes.

A three-solvent system was used to determine the Hildebrand solubility parameters of organic nonelectrolytes. The experimental Hildebrand solubility parameter represents a weighted average of the mole fraction solubilities of the solute in these three individual solvents (ethyl acetate, 1-propanol, and 1,2-propanediol). The solvent system estimated the Hildebrand solubility parameters of solutes within a range from 8.9 to 14.8 (cal/cm3)2(1). Deviations ranged from 0.8 to 12.9%, with the highest value at the extreme and well within 10% at the median. Estimation of the Hildebrand solubility parameters of solutes within a wider range and with somewhat better accuracy was made with a five-solvent system (hexane, ethyl acetate, 1-propanol, 1,2-propanediol, and water).

Methods↗
PubMed1993

[Pulmonary edema in transcervical endometrial ablation: a case report].

The use of the transcervical resectoscope for endometrial ablation and/or resection of myomas is a relatively new technique in gynecologic surgery. Although complications are uncommon with this procedure, they can occasionally appear and lead to potential hazard. Here a patient presenting for endometrial ablation is described; 1.5% glycine was used as the irrigation solution to enhance visibility and to wash away blood and tissue particles. Unfortunately, a large amount of glycine was absorbed by the open vessels in the myometrium during operation, leading to pulmonary edema and dilutional hyponatremia. After administration of diuretics, sodium supplement and 100% oxygen, complications improved progressively. The patient was discharged on postoperative day 5 without any sequelae.

Adult↗
PubMed1992

Glucocorticoid stimulates hepatitis B viral gene expression in cultured human hepatoma cells.

Glucocorticoids have been shown to influence the severity of hepatitis B virus-related chronic hepatitis in human. However, very little is known about the effects of glucocorticoids on hepatitis B virus replication in vitro. In this report, we used a well-differentiated human hepatoma cell line, Hep3B, transfected with hepatitis B virus complementary DNA as a model to show that a glucocorticoid analog, dexamethasone, can directly stimulate the production of HBsAg and HBeAg. Elevation of 3.5-kb pregenomic RNA and all other viral RNAs in the transfected Hep3B cells after dexamethasone treatment supports the hypothesis that glucocorticoids directly stimulate hepatitis B virus gene expression in vitro. The concentration of dexamethasone for its half-maximal stimulatory activity toward HBsAg, HBeAg and all viral transcripts was approximately 10(-8) mol/L, close to the affinity of glucocorticoid receptors to [3H]-triamcinolone acetonide in Hep3B cells (approximately 10(-8) mol/L). Specific glucocorticoid antagonist RU38486 completely blocked dexamethasone-induced HBV gene expression, suggesting that the stimulatory effect of dexamethasone was mediated through specific glucocorticoid receptors.

Carcinoma, Hepatocellular↗
PubMed1992

Scrub typhus and pregnancy: a case report and literature review.

Scrub typhus is still prevalent on Penghu Islands. We herein report a case in a pregnant woman who had been to Yi-Lan County in Taiwan. The patient responded well to Minocycline (Minocin) therapy without complication. Her newborn baby was found not complicated with the disease. The relative literature is reviewed.

Adult↗
PubMed1992

[Transcervical resection of endometrium and submucous myomas].

Transcervical resection of the endometrium and submucous myomas using an unmodified urologic resectoscope has recently been developed as a treatment for menorrhagia and/or infertility when conservative management proves unsatisfactory but the patient desires to preserve the fertility or wishes to avoid hysterectomy. Through June 1990, 7 patients were treated with this procedure including one for endometrial ablation and six for transcervical myomectomy alone. No significant complication was seen and the results were relatively satisfactory in an average 7 1/2 months follow up. This approach seems a safe, effective surgical procedure and represents an attractive alternative to hysterectomy or abdominal myomectomy.

Adult↗
PubMed1986

[Dengue vector density survey in Liuchiu, Pintung, Taiwan].

The first outbreak of dengue in Taiwan in 35 years was recorded in the summer of 1981 in Liuchiu, Pintung, a small offshore island of southern Taiwan. An investigation team visited the affected area during the period of 14-17 October 1981 and collected 8,641 mosquito larvae, of which 4,432 were Aedes aegypti and 4,182 were Ae. albopictus. The house index, container index and Breteau index were 44.2, 23.9 and 73.0 for Ae. aegypti and 41.3, 17.0 and 51.9 for Ae. albopictus, respectively. Both species of mosquitoes are peridomestic breeders, with larvae found in water-holding containers in or outside houses. Ae. albopictus is indigenous, but Ae. aegypti may be of recent introduction to the island. As the two species are closely related, the larvae of both species were found co-existent in only 2.3% of positive containers. This supports the hypothesis of the "competitive exclusion principle", i.e., competition is possibly occurring on this island.

Animals↗