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Biomedical subjects

J T Lin

Publications and source records attributed to J T Lin.

At least 91 records · Page 5Linked to original sources
PubMed1998

Glans sculpting in phalloplasty--experiences in female-to-male transsexuals.

An aesthetically appealing neophallus with an urethral meatus at its tip is one of the goals of phalloplasty in female-to-male transsexuals. From July 1993 to December 1996, 20 cases of female-to-male transsexuals who had received sculpting of glans in four different ways were enrolled. Their photographs were collected and were scored by independent surgical and non-surgical assessors. The Norfolk procedure creates a more normal neoglans assessed by patients themselves and by the assessors. Split-thickness skin graft (SSG) produces a more normal-looking coronal sulcus than full-thickness skin graft (FTSG) in the Norfolk procedure.

Adult↗
PubMed1998

Relatively low expression of multidrug resistance-1 (MDR-1) and its possible clinical implication in gastric cancers.

The mechanism of drug resistance of gastric cancer cells has rarely been investigated. We specifically examine the magnitude and the biologic significance of multidrug resistance-1 (MDR-1) expression in human gastric cancer. All patients had previously been treated in prospective clinical trials for advanced gastric cancer in our institution. Patients with adequate prechemotherapy gastric cancer tissues for immunohistochemical studies by a C219 monoclonal antibody were selected for the determination of the expression rate of MDR-1. The results were designated as negative or positive by the independent interpretation of two pathologists. A subgroup of patients who had been treated with doxorubicin- or etoposide-containing regimens were selected for further correlation with drug sensitivity. Between 1990 and 1996, a total of 60 patients, 38 men and 22 women with a median age of 55 years, were studied. Eight (13.3%; 95% confidence interval, 6%-25%) of them had MDR-1 expression. None of the pertinent clinicopathologic features, including the histopathologic types of the tumors and the extent of the diseases, correlated with the expression of MDR-1. Among the 30 patients who had received doxorubicin- or etoposide-containing combination chemotherapy, 3 (10%; 95% confidence interval, 3%-27%) were designated positive for MDR-1 expression. None of the 3 patients responded to chemotherapy, whereas 19 (70.4%) of the 27 patients who had not expressed MDR-1 did respond (p=0.041 by Fisher's exact test). We conclude that the expression of MDR-1 in gastric cancer is relatively low. Its expression, however, is clinically relevant and is useful in predicting the chemoresistance of patients with gastric cancer receiving doxorubicin- or etoposide-containing combination chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Loss of pS2 protein expression is an early event of intestinal-type gastric cancer.

To investigate the prevalence of pS2 expression in gastric cancer with respect to tumor histopathology, intestinal metaplasia and Helicobacter pylori (H. pylori) infection, pathologic specimens of 91 patients with gastric cancer were immunostained for pS2. Such immunoreactivity was correlated with the status of H. pylori infection, tumor staging, histology, subtyping, and associated intestinal metaplasia. Positive pS2 staining was seen throughout all non-neoplastic epithelia, and in all 9 patients with the complete type of intestinal metaplasia. In contrast, 21 of 45 incomplete type of intestinal metaplasia had negative pS2 staining (P < 0.001), and 54 out of 91 tumors (59.3%) showed loss of pS2 expression in the cancer tissues proper. There was no correlation of pS2 expression with age, gender, depth of invasion, duodenal involvement, lymph node metastasis, venous invasion or H. pylori infection. Negative pS2 staining was significantly higher in the intestinal (74.5%) and Borrmann type I, II, III (64.2%) tumors than the diffuse (43.2%, P < 0.005) and Borrmann type IV (20%, P < 0.05) tumors. Our results indicate that loss of pS2 expression may occur as an early event in the malignant transformation process of intestinal-type tumors.

Adult↗
PubMed1998

Overexpression of mutant p53 and c-erbB-2 proteins and mutations of the p15 and p16 genes in human gastric carcinoma: with respect to histological subtypes and stages.

Although the mechanism remains obscure, two histological subtypes of gastric carcinoma (GC), the diffuse and intestinal types, differ drastically in epidemiological, clinical, pathological and biological characteristics. We investigated whether the genetic alterations of several oncogenes and tumour suppressor genes could be correlated with the two histological subtypes. In 60 patients with GC, the overexpression of mutant p53 and c-erbB-2 oncoproteins was studied using immunohistochemical stains. Mutations of the p15 and p16 tumour suppressor genes were assessed by polymerase chain reaction, Southern blotting, and direct DNA sequencing. Overexpression of c-erbB-2 and p53 was found in 21 (35.0%) and 27 (45.0%) patients, respectively. Overexpression of the c-erbB-2 oncoprotein was more common in the intestinal type (15/32, 46.9%) and the advanced stage (19/45, 42.2%) than in the diffuse type (6/28, 21.4%) and the early stage (2/15, 13.3%) of GC (P<0.05). Similarly, p53 overexpression was more frequently found in the intestinal type (19/32, 59.4%) and the advanced stage (24/45, 53.3%) than in the diffuse type (8/28, 28.6%) and the early stage (3/15, 20.0%) of GC (P<0.05). Homozygous deletions of p16 in exon 1 were found in six (10.0%) patients. Five of them had the intestinal-type advanced GC. Neither point mutations of p16 nor alterations of p15 were detected. The frequency of alterations of p53, c-erbB-2, and p16 was not related to sex and Helicobacter pylori infection. No correlation of genetic changes between any two genes was observed. Our preliminary results indicate alterations in the p15 gene were not important in gastric tumorigenesis, while infrequent homozygous deletions in the p16 gene play a limited role in tumour progression of intestinal-type GC. Moreover, overexpression of c-erbB-2 and p53 is frequently encountered in the intestinal-type advanced GC. Alterations of p53, c-erbB-2 and p16 genes may function independently of each other in gastric carcinogenesis. The association between genetic alterations and histological subtypes supports the notion that a distinct pathogenesis may exist in different histological subtypes.

Aged↗
PubMed1998

Optimized conditions for growth and fermentation of Helicobacter pylori.

This study attempted to optimize the growth conditions of Helicobacter pylori by comparing the growth of H. pylori in an anaerobic jar and an incubator. It was found that the primary isolation rate of H. pylori from gastric biopsies was higher in an anaerobic incubator (28/30) than in an anaerobic jar (21/30). In addition, growth rate in the subsequent passage was also higher in an incubator. By comparing different supplements in the liquid media, it was found that most strains grew best in Brucella broth containing 5% fetal calf serum, and some strains grew well with the supplement of 0.2% of beta-cyclodextrin. A large scale culture using a bioreactor indicated that a defoaming agent, polypropylenglycol, profoundly inhibited the growth of H. pylori. However, fermentation could be successfully performed by continuously infusing mixed airs composed of 5% O2, 10% CO2 and 85% N2. Moreover, the production of secreted proteins of H. pylori strains grown in the bioreactor was the same as that in an anaerobic jar. Results presented herein can be used to further optimize conditions for enhancing the growth of H. pylori.

Fermentation↗
PubMed1998

Radiographic and computed tomographic findings of gastric mucosa-associated lymphoid tissue lymphomas.

The purpose of this retrospective study was to evaluate the detection of gastric mucosa-associated lymphoid tissue (MALT) lymphoma lesions by upper gastrointestinal (UGI) radiography and computed tomography (CT). Fifteen patients with endoscopic biopsy-proven MALT lymphoma were included. Fourteen of these patients underwent double-contrast UGI radiography and 14 were examined with CT of the upper abdomen; 13 underwent both procedures. UGI radiography identified 88% (30/34) of lesions detected by endoscopy, including 12 of 13 enlarged rugal folds and 15 of the 17 multinodular lesions, but failed to identify two of the three ulcerative lesions. UGI radiography identified the only submucosal lesion demonstrated by endoscopy, as well as one at the gastric antrum that had been missed by endoscopy. CT demonstrated nine of 30 endoscopically proven MALT lymphoma lesions, three with focal thickening of the gastric wall and six with a lobulated inner gastric wall. CT failed to demonstrate two fundal and 19 antral or gastric body lesions. Our findings suggest that the predominant UGI features of gastric MALT lymphoma are enlarged folds and multinodular lesions. Although UGI radiography does not reveal all MALT lymphoma lesions, it may find lesions that are not detected by endoscopy. Mucosal lesions of gastric MALT lymphoma are usually not detected by CT.

Adult↗
PubMed1998

Pharmacological properties of ACh receptors on the heart of the marine bivalve Meretrix lusoria.

The cholinergic receptors on the heart of the marine bivalve Meretrix lusoria were used as a model to investigate their pharmacological properties in bivalves. By recording method, we measured the contractile force (CF) and the heart rate (HR) of the heart to examine the characteristics of cholinergic receptors of a marine bivalve. The known ACh receptor agonists or antagonists in vertebrate nervous system were then introduced into the heart by perfusion, to monitor their effects upon heart activities. Of the six tested agonists, two mAChR agonists (OXA-22, bethanechol) and two nAChR agonists (methylcarbachol, nicotine) mimicked the response induced by ACh. Among the seven tested antagonists, three mAChR antagonists (trihexyphenidy1, atropine and scopolamine) and three nAChR antagonists (TEA, curare and hexamethonium bromide) showed the antagonistic effects on the inhibition induced by ACh. However, there was one mAChR agonist, metoclopramide, that behaved like an ACh antagonist. Both APE (mAChR agonist) and PTMA (nAChR antagonist) showed no significant effects. This differences suggest that the pharmacological characteristics of ACh receptors on the heart of bivalve are different from those in vertebrates. It may be a novel type of ACh receptors.

Acetylcholine↗
PubMed1998

Molecular mechanisms of clarithromycin resistance in Helicobacter pylori.

Combination antibiotic therapy for Helicobacter pylori has now become the standard means of treating peptic ulcer diseases. Clarithromycin is a newly adopted antibiotic for H. pylori eradication. However, resistance to clarithromycin reduces the efficacy of clarithromycin-containing regimens. We explored mechanisms of clarithromycin resistance by evaluating H. pylori for macrolide resistance mechanisms reported in H. pylori and other bacteria. Degenerate polymerase chain reaction analysis of the H. pylori genome failed to yield products homologous to methylase, a drug inactivation enzyme, or efflux pumps. Clarithromycin selection in Escherichia coliNM522, transformed with an expression library that was constructed with genomic DNA from a clarithromycin-resistant strain of H. pylori, revealed six clones that conferred clarithromycin resistance consistently after retransformation. Southern hybridization and DNA sequencing revealed that four of the six clones contained the same locus. Comparison of DNA and amino acid sequences showed that the 1.3-kb DNA fragment had significant homology to the 3-oxoadipate CoA-transferase subunit A (yxjD) and subunit B (yxjE) of Bacillus subtilis. However, the clarithromycin inactivation assay and knockout mutation analysis showed that the gene increased clarithromycin resistance in E. coli, but not in H. pylori. In contrast, sequencing of the 23S rRNA gene in six clarithromycin-resistant H. pylori clinical isolates revealed an A to G transitional mutation at position 2515 of the 23S rRNA gene in all isolates. Natural transformation with the 23S rRNA gene from resistant strains conferred clarithromycin resistance in clarithromycin-sensitive strains. We conclude that the 23S rRNA mutation is sufficient to confer clarithromycin resistance and that it is the major mechanism of clarithromycin resistance in H. pylori.

Amino Acid Sequence↗
PubMed1997

Loss of imprinting and overexpression of IGF2 gene in gastric adenocarcinoma.

Both insulin-like growth factor II (IGF2) and H19 gene are located on chromosome 11p15.5 in close vicinity to each other, and are imprinted on different parental alleles. Although the exact mechanism remains unclear, loss of imprinting (LOI) leading to the biallelic expression of IGF2 and H19 genes has recently been reported in a variety of tumors. To study the role of IGF2 and H19 genes in gastric carcinogenesis, the LOI and loss of heterozygosity (LOH) status of these two genes were determined in 70 patients with gastric cancer. Among them, 30 patients were heterozygous for IGF2, 28 patients were heterozygous for H19, and 42 patients were heterozygous for either IGF2 or H19 gene. Among the 30 patients who were heterozygous for IGF2, one exhibited LOH (1/30, 3.3%) and 10 exhibited LOI (10/29, 34.5%). None of the 28 patients heterozygous for H19 gene had either LOH or LOI. LOI of IGF2 was more frequently found in the diffuse type (8/15, 53.3%) than the intestinal type (2/14, 14.3%, P < 0.05) gastric cancer. Five out of the six tumors with LOI of IGF2 exhibited overexpression of mRNA, but no obvious alterations of expression of H19 were noted by Northern hybridization. These data suggest that LOI leading to overexpression of IGF2 plays an important role in carcinogenesis of diffuse type gastric cancer.

Adenocarcinoma↗
PubMed1997

Seroprevalences of hepatitis B and C viruses and Helicobacter pylori infection in a small, isolated population at high risk of gastric and liver cancer.

The objective of this study was to examine the seroprevalences of chronic infection with hepatitis B and C viruses and Helicobacter pylori in Matzu, a group of small islets with 5,566 civilian residents who have extremely high mortality from cancers of the stomach and liver. The standardized mortality ratios (SMR) of all cancer sites combined, liver cancer and stomach cancer in 1984-1993 were calculated using the general population in Taiwan as the referent (SMR = 100). The SMRs (95% confidence interval) for all cancer sites combined, liver cancer and stomach cancer were 160 (131-195), 252 (170-360) and 351 (229-516), respectively, in Matzu. A health survey was carried out with 1,485 civilian residents aged 30 years or more, giving a response rate of 69% among those who were eligible. Serum samples were tested for antibodies against Helicobacter pylori (anti-HP) by enzyme-linked immunosorbent assay and hepatitis B surface antigen (HBsAg) and antibodies against hepatitis C virus (anti-HCV) by enzyme immunoassay. The seroprevalence was 61% for anti-HP, 24.7% for HBsAg and 1.8% for anti-HCV in Matzu. While mortality rates of liver and stomach cancers were significantly higher in Matzu than in Taiwan, the seroprevalences of anti-HP, HBsAg and anti-HCV in Matzu were similar to or even lower than those in Taiwan. These findings suggest the existence of risk factors other than microbial agents involved in the development of stomach and liver cancers.

Adult↗
PubMed1997

Synthesis of the photoaffinity label [1'-14C]-6C-(azimethyl)octylglucoside and its reaction with isolated renal brush border membranes.

We describe the synthesis of the photolabile analog of n-octylglucoside (OG), 6C-(azimethyl)octylglucoside (diazirino-octylglucoside, DOG). This diazirino derivative (lambda max = 335 nm) can be activated with long-wavelength UV to generate a highly reactive carbene, an intermediate suitable for a covalent ligand-receptor linkage. In inhibitor studies on D-glucose uptake into rabbit renal brush border membrane vesicles (BBMV) DOG showed a competitive inhibition with regard to D-glucose with a Ki of 20 +/- 5 microM, which was not significantly different from that of the template compound OG (Ki = 30 +/- 10 microM). On irradiation (lambda max = 350 nm) of BBMV in the presence of [14C]DOG, proteins of 61, 72 to 78, and 95 kDa were labeled by photoinduction. A band of 73 kDa was also positive in Western blots using an anti-Na+/D-glucose cotransporter antibody. Further investigations revealed that the labeled proteins were presumably mainly glucosidases known to be present in high concentration in renal BBMV. By comparison with authentic material one of the labeled proteins (61 kDa) was identified as trehalase (EC 3.2.1.28). These studies suggest that labels such as DOG carrying the reactive group directly at the D-glucose moiety of the molecule can be used to label proteins with carbohydrate recognition sites.

Affinity Labels↗
PubMed1997

Infrequent hMSH2 mutations in sporadic gastric adenocarcinoma with microsatellite instability.

The status of genetic instability was determined with seven microsatellite markers from 40 patients with primary gastric adenocarcinoma. For those cases with microsatellite instability, alterations of hMSH2 were further investigated by direct sequencing of reverse transcription-polymerase chain reaction products. Twelve (30%) of 40 patients were found to have microsatellite instability. Among them, one patient (1/6, 16.7%) was early gastric cancer and 11 (11/34, 32.4%) were advanced gastric cancer. There were seven patients with diffuse type (7/18, 38.7%), while five (5/22, 22.7%) were intestinal type tumors. The entire coding region of the hMSH2 gene in these 12 affected individuals was amplified and sequenced. Only a 41-year-old female patient with diffuse type advanced gastric cancer showed a GCT to TCT missense mutation at codon 207 with predicted protein change from alanine to serine. Our results indicate that genetic instability plays an important role in gastric tumorigenesis and alterations of the hMSH2 gene are related to only a small portion of sporadic gastric adenocarcinoma with microsatellite instability.

Adenocarcinoma↗
PubMed1997

Seroprevalence of Helicobacter pylori in patients with surgical peptic ulcer.

BACKGROUND: Helicobacter pylori is known as a major cofactor in ulcerogenesis. However, the role of H pylori in surgical patients with peptic ulcer and its possible influence on surgical treatment is unclear. OBJECTIVES: To determine the prevalence of H pylori infection in surgical patients with complicated peptic ulcer diseases and analyze its clinical significance. DESIGN: A prospective, controlled study. SETTING: University-affiliated hospital and tertiary care center. SUBJECTS: Two study groups: surgical group (n = 66), i.e., patients who received surgical treatment for their peptic ulcer disease), and control group (n = 377) comprising 3 subgroups: normal volunteers (NV subgroup, n = 136) and patients who required only medical treatment for duodenal ulcer (DU subgroup, n = 119) or gastric ulcer (GU subgroup, n = 122) from January 1, 1994 to June 30, 1995. METHODS: Preoperative or overnight fasting serum samples were collected, and H pylori state was assessed by serum anti-H pylori IgG. RESULTS: Seropositivity was similar between the surgical group (60.6%) and NV control subgroup (58.8%), but it was highest in the DU control subgroup (87.4%) (P < .001 compared with NV control subgroup), followed by GU control subgroup (76.2%) (P < .01 compared NV). The patients with surgical peptic ulcer who had both seropositive and seronegative results for H pylori were similar for sex, age, social status, ulcer history, associated major medical problems, use of nonsteroid anti-inflammatory drugs, ulcer location, type of surgery, and ulceration recurrence rate. Although patients who underwent elective surgery had a higher seroprevalence rate (88.9%) than those requiring emergency surgery (56.4%) and patients who were seronegative for H pylori seemed to be associated with a higher major morbidity, these results were not statistically significant. CONCLUSION: No significant association of H pylori infection and peptic ulcer was noted between patients who required surgical treatment compared with those who required only medical treatment; H pylori played only a limited role in the cause of disease in surgical patients, perhaps only in the cases complicated with stenosis or intractable ulcers. This suggests that presently adequate acid reduction procedure will still be the main objective of surgical treatment and prevention of the ulcer recurrence.

Adult↗
PubMed1997

Pathways for fatty acid elongation and desaturation in Neurospora crassa.

Neurospora crassa incorporated exogenous deuterated palmitate (16:0) and 14C-labeled oleate (18:1 delta 9) into cell lipids. Of the exogenous 18:1 delta 9 incorporated, 59% was desaturated to 18:2 delta 9,12 and 18:3 delta 9,12,15. Of the exogenous 16:0 incorporated, 20% was elongated to 18:0, while 37% was elongated and desaturated into 18:1 delta 9, 18:2 delta 9,12, and 18:3 delta 9,12,15. The mass of unsaturated fatty acids in phospholipid and triacylglycerol is 12 times greater than the mass of 18:0. Deuterium label incorporation in unsaturated fatty acids is only twofold greater than in 18:0, indicating a sixfold preferential use of 16:0 for saturated fatty acid synthesis. These results indicate that the release of 16:0 from fatty acid synthase is a key control point that influences fatty acid composition in Neurospora.

Deuterium↗
PubMed1997

Genetic alterations in gastric cancer: relation to histological subtypes, tumor stage, and Helicobacter pylori infection.

BACKGROUND & AIMS: A different spectrum of genetic changes including p53, c-erbB-2, c-met, adenomatous polyposis coli (APC), and deleted in colorectal cancer (DCC) is involved in gastric cancer (GC). The aim of this study was to correlate these alterations with histological subtypes, tumor stages, and Helicobacter pylori infection. METHODS: Specimens of 163 patients with GC were immunostained for p53, c-erbB-2, and c-met, and polymerase chain reaction was performed in them to determine loss of heterozygosity (LOH) of APC and DCC. RESULTS: Overexpression of p53 was more frequent in early intestinal than early diffuse GC and was noted in the stage progression of diffuse but not intestinal GC. Overexpression of c-erbB-2 occurred more commonly in intestinal GC and advanced GC of both types. Overexpression of c-met was greater in diffuse GC, particularly at advanced stage. LOH of APC was more common in intestinal GC irrespective of the stage but rarely in diffuse GC. LOH of DCC occurred primarily in advanced intestinal GC and infrequently in early GC or advanced diffuse GC. Alterations of these five genes were not correlated with H. pylori infection. CONCLUSIONS: A distinct genetic pathway exists in gastric carcinogenesis of different histological subtypes and their tumor progression, in which H. pylori infection may play an equal role or no role.

Adenomatous Polyposis Coli↗
PubMed1997

Visual sensitivities of nur77 (NGFI-B) and zif268 (NGFI-A) induction in the suprachiasmatic nucleus are dissociated from c-fos induction and behavioral phase-shifting responses.

Mammalian circadian rhythms are regulated by a pacemaker in the suprachiasmatic nucleus of the hypothalamus. Recent work from several laboratories has shown that light induces the IEGs, c-fos and jun-B, in the rodent suprachiasmatic nucleus. In hamsters, there is a strong correlation between circadian entrainment and the induction of c-fos and jun-B in the suprachiasmatic nucleus by light. Previous work has shown that the IEGs, nur77 and zif268, both of which encode transcription factors, are also light-inducible in the rat suprachiasmatic nucleus [Rusak, B., McNaughton, L., Robertson, H.A. and Hunt, S.P., Circadian variation in photic regulation of IEG mRNAs in rat suprachiasmatic nucleus cells, Mol. Brain Res., 14 (1992) 124-130.; Sutin, E.L. and Kilduff, T.S., Circadian and light-induced expression of IEG mRNAs in the rat suprachiasmatic nucleus, Mol. Brain Res., 15 (1992) 281-290.]. To characterize the photic-regulation of these genes in the suprachiasmatic nucleus of golden hamsters, we used in situ hybridization to measure nur77 and zif268 mRNA levels with 33P-labeled complementary RNA probes. 5-min monochromatic light pulses at CT19 induced a dramatic increase in both nur77 and zif268 mRNA levels. Peak mRNA levels occurred 45-60 min after light onset for both nur77 and zif268. In addition, the induction of both nur77 and zif268 mRNA levels was gated by the circadian pacemaker. Light pulses during subjective day (CT3 and CT9), which do not cause behavioral phase-shifts, did not significantly alter mRNA levels of either nur77 or zif268; whereas light pulses during the subjective night (CT14 and CT19), which induce phase-shifts, dramatically increased both nur77 and zif268 mRNA levels. In contrast to c-fos induction, which has a photic threshold indistinguishable from that of the behavioral phase-shifting response, nur77 and zif268 mRNA induction were found to have visual sensitivities greater than the phase-shifting response by 1-2 log units (10-100-fold). Although light and circadian phase regulate nur77 and zif268 expression in the SCN, these results demonstrate that their induction is not rate-limiting for photic entrainment of the hamster circadian system.

Animals↗