PubMed Health⌕ Search

Biomedical subjects

H J Lin

Publications and source records attributed to H J Lin.

At least 73 records · Page 4Linked to original sources

Predictive factors for rebleeding in patients with peptic ulcer bleeding after multipolar electrocoagulation: a retrospective analysis.

The role of endoscopic therapy for peptic ulcer bleeding is well-documented. Nevertheless, rebleeding occurs in 10% to 30% of patients, and such patients are at high risk for death without early retreatment or definitive surgery. The aim of our study was to predict which patients would rebleed within 1 month after successful multipolar electrocoagulation of 100 patients with active peptic ulcer bleeding (spurting, oozing, or nonbleeding visible vessel). We had achieved initial hemostasis in 97 patients and carried out univariate and multivariate analyses to predict which patients would rebleed. Rebleeding occurred within 1 month in 17 (17.5%) patients. we correlated 20 clinical and endoscopic factors with rebleeding episodes. With univariate analysis, blood transfusion of 500 ml or more at entry (p < 0.0001) and use of cimetidine (p = 0.01) were statistically significant for rebleeding. With multivariate analysis, use of omeprazole was an independent factor for preventing rebleeding (odds ratio, 7.68; 95% confidence interval, 1.642-35.929). We suggest that omeprazole may help to prevent rebleeding in patients who have had hemostasis with multipolar electrocoagulation.

Anti-Ulcer Agents↗

Variants of N-acetyltransferase NAT1 and a case-control study of colorectal adenomas.

N-acetyltransferase NAT1, together with enzymes CYP1A2 and NAT2, helps convert heterocyclic amines to mutagens. Epidemiologic studies of the association of variants of these enzymes with colorectal cancer may provide indirect support for a heterocyclic amine mechanism. We used single strand conformation polymorphism and heteroduplex analysis to screen fro mutations in the NAT1 coding region in a case-control study (n = 932) of colorectal adenomas, which are precursors to cancer. Thirteen different single-base mutations were found: C97T, C190T, T402C, G445A-G459A-T640G ( a combination of three mutations), C559T, G560A, A613G, A752T, T777C, G781A, and A787G. Function of novel mutations was tested by bacterial production of enzymes and measurements of Km, Vmax, and stability. However, on 24-control individuals and 18 cases carried an inactivating NAT1 mutation. When combined with our data on the NAT2 acetylation polymorphism, we saw no evidence for an association between N-acetyltransferases and prevalence of adenomas. Larger sample sizes are required for further evaluation.

Acetyltransferases↗

The hydrophobic pocket of 24p3 protein from mouse uterine luminal fluid: fatty acid and retinol binding activity and predicted structural similarity to lipocalins.

The conformation of 24p3 protein purified from mouse uterine luminal fluid was studied by circular dichroism spectroscopy in 200-300 nm. At pH 7.4, the spectrum in the UV region appears as one negative band with a minimum mean residue ellipticity of -3,600 deg.cm2.dmole(-1) at 217 nm, suggesting a very low or no helical content, but a considerable amount of beta-form, beta-turn, and unordered form in the protein molecule. This agrees with the predicted secondary structures consisting of only one a-helical segment of residues 150-163 and nine segments of residues 28-35, 50-60, 67-72, 78-86, 94-97, 106-114, 119-125, 136-140 and 166-172 in beta-forms, which would construct two orthonormal beta-sheets to form a less polar beta-barrel. The environments around Trp-31 and Trp-81 of this protein were studied by intrinsic fluorescence and solute quenching. They give an emission peak at 332 nm, and only about 21% of them are accessible to quenching by acrylamide. This together with their low accessibility to either CsCI or KI suggests that they are located in the less polar beta-barrel. Hydrophobic compounds such as fatty acids, retinoids, and cholesteryl oleate in the protein solution diminish the protein fluorescence. Analysis of the fluorescence data suggests that the protein has a binding site for hydrophobic ligand. The association constants for the complex formation are 1.03 x 10(6) MM(-1), 1.92 x 10(5) M(-1), 2.38 x 10(5) M(-1) or 1.25 x 10(5) M(-1) for cholesteryl oleate, oleic acid, retinol, or retinoic acid at pH 7.4. Analysis of the equilibrium binding data from binding assay using [H3]-retinol and [H3]-retinoic acid reveals a singular type of retinoid-binding site in the protein with the association constant of 4.92 x 10(5) M(-1) and 1.17 x 10(5) M(-1) for retinol and retinoic acid, respectively. Trp-31 or/ and Trp-81 is in or very near the binding site and the gross conformation of protein changes considerably as the formation of protein-ligand complex.

Acute-Phase Proteins↗

Intra-assay performance characteristics of five assays for quantification of human immunodeficiency virus type 1 RNA in plasma.

Three kits (Roche AMPLICOR human immunodeficiency virus type 1 [HIV-1] Monitor, Chiron enhanced-sensitivity bDNA, and Organon Teknika NASBA HIV-1 QT) and two in-house assays (from National Genetics Institute and Baylor College of Medicine) were compared with a blinded panel. The results were evaluated as to intra-assay sensitivity, precision, and ability to detect differences in a dilution series.

Evaluation Studies as Topic↗

Glutathione transferase null genotype, broccoli, and lower prevalence of colorectal adenomas.

Cruciferous vegetables, especially broccoli, may prevent cancer through anticarcinogenic compounds. For example, broccoli contains isothiocyanates that induce carcinogen-detoxifying enzymes. Glutathione transferase enzymes conjugate isothiocyanates, leading to excretion. We hypothesized that broccoli consumption in combination with the glutathione transferase M1 (GSTM1) null genotype would be associated with a lower prevalence of colorectal adenomas because of higher isothiocyanate levels. We used a case-control study of mainly asymptomatic subjects aged 50-74 years who underwent a screening sigmoidoscopy at either of two Southern California Kaiser Permanente Medical Centers during 1991-1993. Cases (n = 459) had a first-time diagnosis of histologically confirmed adenomas detected by flexible sigmoidoscopy. Controls (n = 507) had no polyp detected. Subjects had a 45-min in-person interview for information on various risk factors and basic demographic data and completed a 126-item, semiquantitative food frequency questionnaire. Blood samples were used for GSTM1 genotyping. Subjects with the highest quartile of broccoli intake (an average of 3.7 servings per week) had an odds ratio of 0.47 (95% confidence interval, 0.30-0.73) for colorectal adenomas, compared with subjects who reportedly never ate broccoli. When stratified by GSTM1 genotype, a protective effect of broccoli was observed only among subjects with the GSTM1 null genotype (P for trend, 0.001; P for interaction, 0.01). The observed broccoli-GSTM1 interaction is compatible with an isothiocyanate mechanism.

Adenoma↗

Prognostic evaluation in supratentorial astrocytic tumors using p53, epidermal growth factor receptor, c-erbB-2 immunostaining.

Molecular pathology may play an important role in predicting the tumor prognosis, particularly p53, epidermal growth factor receptor (EGFR), and c-erbB-2. We investigated six variables (age, sex, histopathological grade, p53, EGFR, and c-erbB-2) to identify the role of such factors in predicting the outcome of patients with supratentorial astrocytic tumors. Thirty-seven tumors were studied including 9 well-differentiated astrocytomas (WHO grade 2), 19 anaplastic astrocytomas (WHO grade 3), and 9 glioblastomas multiforme (WHO grade 4). In univariate analysis, no statistical significance was found for the prognostic value of the sex (p = 0.2188), age (p = 0.5530), p53 immunostain (p = 0.2194), and c-erbB-2 immunostain (p = 0.4203). A significant correlation with the prognosis was found with respect to the histopathological grade (p = 0.0049) and EGFR expression (p = 0.0284). In multivariate analysis, the histopathological grade was shown to be significant independent variable (p = 0.0152). In WHO grade 2 and 3 astrocytomas, expression of p53 or EGFR was associated with poorer patient outcome. In glioblastomas, expression of p53 was also associated with poorer prognosis. Our studies suggested that conventional histological assessment of supratentorial astrocytic tumors remains the best guide to prognosis. Although no statistical significance was found between the immunostains and survival in variant grades of astrocytomas, there was a trend between p53 or EGFR proteins expression and the decrease of survival time.

Adult↗

Transendothelial migration of lymphocytes from HIV-1-infected donors: a mechanism for extravascular dissemination of HIV-1.

To identify factors that cause HIV-1 to establish perivascular foci of infected cells, we studied the transendothelial migration of blood mononuclear leukocytes (MNL) from 76 HIV+ patients and 41 controls. The fraction of patients' lymphocytes that migrated across endothelial cell monolayers in vitro was significantly increased (p < or = 0.03) compared with that of control donors. Migration of patients' CD4+ T cells was particularly enhanced, whereas the migration of monocytes did not differ between patients and controls. Lymphocyte migration correlated with expression of CD11a/CD18 and CD49d/CD29 and with the quantity of TNF-alpha produced as MNLs migrated through the endothelium. Measurement of HIV-1 proviral DNA copies in the patients' MNLs (n = 26) suggested that in half the cases virus-infected cells accumulated preferentially amidst the migratory leukocytes. We observed the same behavior with normal donor MNLs infected, in vitro, with each of 4 strains of HIV-1. The number of HIV-1 proviral DNA copies per million MNLs was 40 to 178 times higher in the migratory population than in the original population added to the endothelium. To test whether only certain strains of HIV-1 stimulate transendothelial migration of infected cells, we used single strand conformation polymorphism analysis to identify quasispecies of HIV-1 in the MNLs. If all strains of HIV-1 were equal in their ability to stimulate transendothelial migration, we expected to find no differences in the quasispecies present in the original and migratory cell populations. In fact the quasispecies differed in 14 of 19 paired samples, suggesting that only certain HIV-1 quasispecies promote transendothelial migration of infected cells.

Acquired Immunodeficiency Syndrome↗

Aminoguanidine corrects hyperdynamic circulation without ameliorating portal hypertension and portal hypertensive gastropathy in anesthetized portal hypertensive rats.

BACKGROUND/AIMS: Portal hypertension and hyperdynamic circulation (i.e. generalized vasodilation and increased cardiac output and regional organ blood flows) may play an important role in the development of portal hypertensive gastropathy. This study investigated the effect of chronic administration of aminoguanidine, a selective inducible nitric oxide synthase inhibitor, to portal hypertensive rats on hemodynamics and the development of portal hypertensive gastropathy. METHODS: Partial portal vein-ligated or sham-operated rats were randomly assigned to receive either placebo (distilled water) or aminoguanidine (approximately 100 mg/kg per day subcutaneously) for 2 days prior to and 14 days. Hemodynamic studies with a thermodilution technique and gastric morphometric analysis were performed at 14 days after the operation. RESULTS: In rats given placebo, portal vein-ligated rats had a significantly lower mean arterial pressure and systemic vascular resistance associated with a significantly higher cardiac index and portal pressure than sham-operated rats (p<0.05). In portal vein-ligated rats aminoguanidine induced a significant increase in mean arterial pressure and systemic vascular resistance accompanied by a significant decrease in cardiac index (p<0.05) without changes in portal pressure (p>0.05). Despite persistence of portal hypertension, the aminoguanidine-treated portal vein-ligated rats had similar mean arterial pressure, cardiac index, and systemic vascular resistance as seen in placebo-treated sham-operated rats. The mean cross-sectional area of gastric mucosal vessels was significantly higher in placebo-treated portal vein-ligated than in placebo-treated sham-operated rats (p<0.05). Treatment with aminoguanidine did not induce changes in the mean cross-sectional area of gastric mucosal vessels in either portal vein-ligated or sham-operated rats (p>0.05). CONCLUSIONS: The results show that in portal hypertensive rats long-term aminoguanidine therapy corrects the hyperdynamic circulation without inducing changes in portal pressure and ameliorating the development of portal hypertensive gastropathy. This study suggests that, instead of correcting hyperdynamic circulation, treatment of portal hypertensive gastropathy should be aimed at reducing portal pressure.

Animals↗

Risk factors for primary lung cancer among non-smoking women in Taiwan.

BACKGROUND: Although cigarette smoking is considered to be the most important cause of lung cancer, smoking behaviour cannot fully explain the epidemiological characteristics of lung cancer in Taiwanese women, who rarely smoke but contract lung cancer relatively often. There are other causes of lung cancer that have produced variability in lung cancer incidence. METHODS: A case-control study involving interviews with 117 female patients (including 106 non-smoking) suffering from lung cancer and the same number of individually matched hospital controls was conducted in Kaohsiung, Taiwan between 1992 and 1993. The questionnaire administered to cases and controls collected information on cigarette smoking and suspected risk factors for lung cancer. Multivariate logistic regression analysis was applied to assess smoking for all women and suspected risk factors for non-smoking women. RESULTS: The relationship between cigarette smoking and lung cancer was statistically significant although only a small proportion (9.4%) of female patients had smoked. However, the risk of contracting cancer for non-smoking women appears to be associated with certain cooking practices, especially preparing meals in kitchens not equipped with a fume extractor at cooking age of 20-40 years (odds ratio [OR] = 8.3; 95% confidence interval [CI]: 3.1-22.7. These factors and a history of pulmonary tuberculosis plus low consumption of fresh vegetables explained 78% of the summary attributable risks for non-smoking women in a multivariate logistic regression model. CONCLUSIONS: Exposure to fumes from cooking oils, when not reduced by an extractor, may be an important factor in causing lung cancer in non-smoking Taiwanese women.

Adult↗

Complex formation between a formyl peptide and 24p3 protein with a blocked N-terminus of pyroglutamate.

We have purified 24p3 protein from mouse uterine fluid (Biochem. J. 316, 545-550, 1996). It is a 25.8-kDa glycoprotein with a N-blocked terminus. This work demonstrated the N-blocked residue to be pyroglutamate, supporting the post-translational cleavage site at Ala-Gln in the precursor protein to generate a putative protein of 180 amino acid residues. Consequently, the two cysteines, Cys78 and Cys177, and the two tryptophans, Trp31 and Trp81, are assigned along the polypeptide chain. No free thiol group was detected in the protein. The presence of formyl-Met-Leu-Phe in the protein solution causes a considerable decrease in the protein fluorescence due to Trp31 and Trp81. Analysis of the fluorescence data supports the idea that the protein can be complexed with the formyl peptide. The association constant for the complex formation is (4.8 +/- 0.29) x 10(5) M-1 at pH 7.4.

Acute-Phase Proteins↗

Improved methods for quantification of human immunodeficiency virus type 1 RNA and hepatitis C virus RNA in blood using spin column technology and chemiluminescent assays of PCR products.

The quantification of human immunodeficiency virus type 1 (HIV-1) RNA or hepatitis C virus (HCV) RNA has been facilitated by adapting a spin column procedure for sample preparation and the use of chemiluminescent detection of polymerase chain reaction (PCR) products in microtiter plate format. All materials were commercially available and relatively inexpensive. By making a single dilution prior to amplification, concentrations of 500 copies to 2.5 million HIV-1 1 RNA copies per mL and 1,000 copies to 50 million HCV RNA copies per mL could be determined on 140-microL samples. Between-run imprecision employing the improved procedure for HIV-1 RNA was 23%. Correlation of HIV-1 RNA concentrations obtained using chemiluminescent detection with values obtained by colorimetric assay of PCR products was 0.98. Correlation of HCV RNA concentration determined by the spin column-chemiluminescent assay procedure with those obtained by branched DNA methodology was 0.91. Spin columns could be used with serum or plasma containing acid-citrate-dextrose or heparin anticoagulant, but heparinized samples required treatment with heparinase prior to amplification.

Anticoagulants↗

Novel p53 mutation in a malignant tumor secreting vasoactive intestinal peptide.

OBJECTIVE: To assess involvement of p53 mutations in development of pancreatic endocrine tumors. DESIGN: Survey of sporadic pancreatic endocrine tumors. SETTING: Hospital referral centers, mainly in the Los Angeles, Calif, area. PATIENTS: We obtained fresh surgical specimens from 25 patients (convenience sample) with no family history of endocrine tumors and no evidence of multiple endocrine neoplasia 1 or von Hippel-Lindau disease. Preoperative tests included serum peptide analysis. MAIN OUTCOME MEASURES: DNA was prepared from tumor specimens. We screened exons 5 through 8 of the p53 gene using single-strand conformation polymorphism analysis, followed by DNA sequencing when a variant was detected. RESULTS: A three-base deletion mutation (codon 239) was found in one malignant tumor secreting vasoactive intestinal peptide. CONCLUSIONS: p53 appears to have a limited role in development of pancreatic endocrine tumors. However, evidence from one of our patients suggests it may be involved in tumor progression in uncommon cases.

Codon↗

Clarithromycin in the combination therapy for the eradication of Helicobacter pylori in peptic ulcer disease.

BACKGROUND: Clarithromycin is a new macrolide antibiotic which is known to be highly effective in eradicating Helicobacter pylori (H. pylori). In Chinese, the role of clarithromycin for H. pylori is still unclear. METHODS: Between January 1995 and February 1996, 75 patients with active H. pylori-positive duodenal ulcer were enrolled in this study. Three groups were randomized to have (1) 2 x 150 mg nizatidine twice daily, 2 x 250 mg amoxicillin four times daily, and 2 x 250 mg clarithromycin three times daily for two weeks (niz-amox-clar group, N = 25); or (2) 20 mg omeprazole twice daily plus 2 x 250 mg clarithromycin three times daily for two weeks (ome-clar group, N = 25); or (3) 300 mg bismuth subsalicylate four times daily, and 2 x 250 mg amoxicillin four times daily, 250 mg metronidazole four times daily for two weeks (triple therapy group, N = 25). All the patients received H2 receptor antagonist (150 mg nizatidine or ranitidine, or 400 mg cimetidine, twice daily) for the consecutive six weeks. RESULTS: The eradication rate of H. pylori eight weeks after the entry of study was 80%(20/25) in the niz-amox-clar group, 76%(19/25) in the ome-clar group, 88%(22/25) in the triple therapy group (p < 0.05 among the three groups). The ulcer healing rates eight weeks after the entry of study for the niz-amox-clar, the ome-amox, and the triple therapy groups were 84%(21/25), 80%(20/25), and 80%(20/25), respectively (p < 0.05 among the three groups). The number of patients experiencing adverse effects in the niz-amox-clar group, the ome-clar group, and the triple therapy group were 10(40%), 7(28%), and 4(16%), respectively (p > 0.05 among the three groups). CONCLUSIONS: Both nizatidine/amoxicillin/clarithromycin and omeprazole/clarithromycin regimens can achieve good eradication rates and may provide an effective alternative anti-H. pylori treatment in duodenal ulcer diseases.

Adult↗

Expression of epidermal growth factor receptors and c-erbB-2 proteins in human astrocytic tumors.

Tumorigenesis is the result of sequential or multiple genetic alterations. The overexpression or amplification of various oncogenes in diverse human brain tumors have been observed. While numerous studies on the immunohistochemical demonstration of EGFR-overexpression have been reported, little has been found in the literature about the c-erbB-2 protein in human astrocytic tumors. In the present study, we evaluated the expression of EGFR and c-erbB-2 protein in 33 astrocytic tumors with immunohistochemistry. According to the World Health Organization brain tumor classification, the study included 9 low-grade astrocytomas (grade 2), 15 anaplastic astrocytomas (grade 3), and 9 glioblastomas multiforme (grade 4). The positive EGFR immunoreactivity was detected in 28 (85%) of 33 tumors. The expression of EGFR increased with the grade of malignancy in low-grade astrocytomas (67%), anaplastic astrocytomas (87%), and glioblastomas (100%). For the expression of c-erbB-2 protein, 17 (51.5%) of 33 tumors were positive immunostain, including 3 low-grade astrocytomas (37.5%), 9 anaplastic astrocytomas (81.8%), and 5 glioblastomas (62.5%). Different degrees of immunoreactivity for c-erbB-2 protein were found in variant grades of astrocytomas. However, the positive immunostain of EGFR displayed moderate or strong reactivity. The coexpression of EGFR and c-erbB-2 protein was found in 17 (15.5%) of 33 tumors. The results emphasize that the overexpression of EGFR parallels astrocytoma progession and higher frequency of c-erbB-2 immunoreactivity was seen in snaplastic astrocytomas and glioblastomas than in low-grade astrocytomas.

Adolescent↗

Conformational change and inactivation of membrane phospholipid-related activity of cardiotoxin V from Taiwan cobra venom at acidic pH.

The phospholipid binding activity of cardiotoxin V from Naja naja atra (CTX A5) was studied by use of Langmuir monolayers and found to exhibit pH-dependence in binding to phosphatidylcholine membrane with an apparent pKa around 6.0. Proton NMR investigation of the CTX A5 molecule in the presence of phosphatidylcholine micelles reveals a decrease in association of CTX A5 with membranes at low pH as a result of the protonation of His-4 near the membrane binding site of loop I region of CTX. The pH-dependent binding can be attributed mainly, but not solely, to the change in charge content of the CTX molecule upon His-4 protonation at the membrane/water interface. This is shown by analyzing the pH- and ionic strength dependence of binding of CTXs to phospholipid monolayers according to Gouy-Chapman theory. The protonation of the His-4 residue also results in a local conformational change in the loop I region since the chemical shifts of amide protons for the amino acid residues from Cys-3 to Thr-14 are all found to vary as a function of pH with an apparent pKa similar to that of His-4. Interestingly, the effect is relayed to other amino acid residues in the structural core of the protein such as those in C-terminal (Lys-60, Cys-61, and Asn-62) and triple-stranded antiparallel beta-sheet (Cys-22, Lys-24, Ala-25, Arg-38, and Ala-41) regions. An additional local conformational change in the molecule results around pH 5 as evidenced by circular dichroism spectroscopic studies, although this change does not affect the characteristic beta-sheet and three-finger loop structure of CTX molecule as revealed by two-dimensional NOESY 1H NMR study. The latter conformational change at acidic pH, however, completely inactivates CTX-induced aggregation/fusion activity of sphingomyelin vesicles. The results suggest that deciphering the functional sites of CTXs on the basis of structure and dynamics determined at low pH should be done with caution. Since 19 out of 44 CTX homologues with known amino acid sequence contain His-4, the effect of His-4 on the structure and function of CTX molecules is important and is discussed in terms of the diverse membrane targets of CTX subtypes. Also discussed is the pH-induced activation of snake venom proteins in the victim.

Animals↗

The role of acidic amino acid residues in the structural stability of snake cardiotoxins.

We have recently shown that membrane-related activities of cardiotoxin V from Naja naja atra (CTX A5) are diminished at acidic pH although the overall beta-sheet structure of the molecule is maintained. In order to understand more about the mechanism of inactivation of CTX at acidic pH, we studied the effect of pH and denaturing reagents on the structural stability of CTX. We found, first, pH-induced structural transitions occurred in CTX A5 at two pH values as judged by the CD ellipticity around 195 nm: an increase in the beta-sheet content occurred around pH 4 and followed by a decrease, therein, around pH 2. The pKa of three acidic amino acid residues in CTX A5, i.e., Glu-17, Asp-42, and Asp-59, were determined to be 4.0, 3.2, and below 2.3, respectively, by NMR spectroscopy. The low pKa value of Asp-59 implies salt bridge formation between Lys-2 and Asp-59. Thus, electrostatic interaction may stabilize the three loop structure in addition to the hydrogen bonds between N- and C-termini of CTX molecule. Second, 2,2,2-trifluoroethanol (TFE) and guanidinium chloride (GdmHCI) were found to induce alpha-helical and random coil formation, respectively, in CTX A5 and eight other beta-sheet CTXs. Comparison of the relative potencies of TFE and GdmHCI to induce structural changes suggests that the amino acid residue located at position 17 plays a role in the structural stability. Specifically, CTXs containing negatively charged Glu-17 are least stable. It is suggested that Glu-17 may perturb the interaction between Lys-2 and Asp-59, and thus the overall stability of beta-sheet, in the presence of denaturing reagent. In conclusion, the perturbed structural stability of CTXs may partially explain the lower activity CTX exhibits at acidic pH. A structural model to account for the unfolding and refolding of CTX molecules without the breaking of disulfide bonds is also proposed.

Amino Acid Sequence↗

Kernel density analysis of variable and conserved regions of the envelope proteins of human immunodeficiency virus type 1 and associated epitopes.

A new statistical approach to the study of conservation of amino acid and nucleotide sequences based on kernel density analysis is described that enables analysis of both conserved and highly variable HIV-1 protein sequences. The amino acid sequences of HIV-1 env proteins in 63 isolates were analysed to determine, first, whether the designations of regions identified in 1987 as conserved (C1-C6) or variable (V1-V5) were still valid. Even though the data base used was nine times larger, the designations that were based on seven isolates from five patients remain correct. Second, the new approach enabled the quantifications of the degree of conservation in reported B or T cell epitopes. Using this approach, highly conserved epitopes located in both gp41 and gp120 were identified.

Amino Acid Sequence↗