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Biomedical subjects

J T Lin

Publications and source records attributed to J T Lin.

At least 109 records · Page 6Linked to original sources

Distinct clinicopathologic characteristics of diffuse- and intestinal-type gastric cancer in Taiwan.

The clinicopathologic features of 221 patients with intestinal-type (IT) gastric cancer were compared retrospectively with those of 290 diffuse type (DT). Intestinal type was characterized by an older mean age (65.0 +/- 10.8 years vs. 56.2 +/- 13 years), a higher male-female ratio (2.56 vs. 1.06), predominance of blood group O (46.2% vs. 31.1%), and frequent habitual smoking (50.7% vs. 31.4%) and drinking (28.5% vs. 17.6%) than did DT. In contrast, DT had a higher frequency of positive history of parent or sibling with gastric cancer (9.3% vs. 4.1%) and blood group A (40.3% vs. 27.6%) than did IT. The distinguishing histologic features of DT included more Borrmann type IV (13.1% vs. 1.3%) but less Borrmann type I (1% vs. 7.2%), more frequent involvement of middle third (26.9% vs. 15.9%) and whole stomach (4.1% vs. 0%), and more peritoneal seeding (15.5% vs. 9%), lymph node metastasis (67.2% vs. 51%), and nerve permeation (34.1% vs. 24.4%), but less Helicobacter pylori infection (55.9% vs. 69.2%) when compared with those of IT. There was no difference in depth of tumor invasion, venous permeation, duodenal involvement, and postoperative survival between IT and DT. These distinct clinicopathologic features between IT and DT in Taiwan suggest the presence of a different pathogenic process for these two histologic subtypes of gastric cancer.

Adenocarcinoma↗

Increased prevalence of Helicobacter pylori infection among patients affected with intestinal-type gastric cancer at non-cardiac locations.

Previous data on the association of Helicobacter pylori infection with gastric cancer by demographic or histological features are inconsistent due to a univariate analysis of limited case numbers. The aim of the present study was to determine such an association by the use of a large series of patients and multiple variables analysis. The serum IgG antibodies against H. pylori were measured in 397 patients with histologically verified gastric cancer. A multiple logistic regression analysis was used to define the association between seropositivity and demographic or tumour characteristics of gastric cancer. The overall seropositivity of H. pylori was 63%. In univariate analysis, the prevalence was significantly lower among patients with cardia (50%) or diffuse-type (56.6%) cancers than those with non-cardia (64.8%) or intestinal-type (70.3%) cancer (P < 0.05 and P < 0.01, respectively). There was no statistical difference between H. pylori infection rate and gender, age or tumour stage. A multiple logistic regression analysis showed tumour location and histology remained significant factors associated with seropositivity of H. pylori with an odds ratio of approximately 2.0. Analysis of combined histology and location revealed that patients with intestinal-type cancer at non-cardia locations had the highest odds ratio of 3.93 (95% confidence interval (CI): 1.55-10.0) compared with the lowest odds ratio of 0.69 (95% CI: 0.30-1.62) in diffuse cardia cancer (P < 0.005). Our data indicate H. pylori infection in gastric cancer is independently affected by the histological subtype and by tumour location.

Adult↗

Acute pancreatitis complicated by infarction of the spleen and spinal cord.

Complications of acute pancreatitis may include local pancreatic necrosis with pseudocyst or abscess formation, and extrapancreatic manifestations such as pulmonary renal, hepatic, endocrine, and coagulation abnormalities. Coagulation abnormalities associated with acute pancreatitis usually present as thrombophlebitis or widespread microthrombi; most occur in the venous or capillary circulation. We report a rare case of acute pancreatitis complicated by pseudocyst formation, splenic vein thrombosis, splenic infarction, and spinal cord infarction, which resulted in paraplegia. An association between acute pancreatitis and spinal cord infarction has not been reported before.

Acute Disease↗

Interactions of alkylglucosides with the renal sodium/D-glucose cotransporter.

To study the nature of the glucose binding pocket of the renal Na+/D-glucose cotransporter, we have evaluated the inhibitory potency of various alkylglucosides (AG) on sodium-dependent D-glucose uptake into hog kidney brush border membrane vesicles (BBMV). Inhibition at 0.1 mM AG level was found to be strongly dependent on the anomeric configuration, on the length and on the flexibility of the side chain. Beta-n-AG inhibited transport significantly more effectively compared to the corresponding alpha-anomer (n-octylglucoside: alpha-anomer 15%, beta-anomer 84%) and AG with an unsaturated n-alkenyl side chain were significantly less effective inhibitors than the corresponding saturated compound (cis/trans 3-n-beta-hexenylglucoside 53% and 32%, beta-n-hexylglucoside 76%). A series of beta-n-AG increasing in side chain length from 1 to 13 carbon atoms revealed a global maximum in the inhibition pattern when beta-AG with side chains ranging from 8 to 11 carbon atoms were used, thus beta-methylglucoside inhibited glucose transport by 13%, beta-n-nonylglucoside by 92%, and beta-n-tridecylglucoside showed no effect. Kinetic analysis of inhibition by beta-n-octylglucoside revealed a fully competitive type of inhibition with an apparent K(i) of 10 +/- 2 microM. n-Octylglucoside at 0.1 mM did not inhibit sodium-dependent L-alanine uptake; similarly, n-octylmannoside at 0.1 mM level did not affect D-glucose uptake. These results suggest that the inhibition of sodium-dependent D-glucose uptake was, at least in the concentration range tested (up to 0.1 mM), not due to a detergent effect of AG, but due to interaction with the carrier. Optimum interaction requires a beta-anomer with a glycosidic bond that places the alkyl chain into an equatorial position with regard to the D-glucose molecule and the two main determinants of the sugar recognition site C2 and C3. In addition, the alkyl chain has to be highly flexible. The alkyl chains thus apparently interact with hydrophobic sites at the carrier in a slightly coiled conformation, thereby AG with a chain length up to 6 carbon atoms interact only with one hydrophobic site, AG with higher chain length probably with two sites.

Animals↗

Nitrate and nitrite-mediated transcription antitermination control of nasF (nitrate assimilation) operon expression in Klebsiella pheumoniae M5al.

Klebsiella pneumoniae can use nitrate and nitrite as sole nitrogen sources during aerobic growth. Nitrate is converted through nitrite to ammonium by assimilatory nitrate and nitrite reductase, respectively. Enzymes required for nitrate assimilation are encoded by the nasFEDCBA operon of K. pneumoniae; nasF operon expression is subject to both general nitrogen control and pathway-specific nitrate/nitrite induction, mediated by the NtrC and NasR proteins, respectively. Sequence inspection revealed a presumptive sigmaN (sigma54)-dependent promoter as well as two presumptive upstream NtrC protein binding sites. Site-specific mutational and primer extension analyses confirmed the identity of the sigmaN-dependent promoter. Deletions removing the apparent NtrC protein binding sites greatly reduced NtrC-dependent regulation, indicating that these sites are involved in general nitrogen control. However, deletions removing most of the sequence upstream of the promoter had little effect on nitrate/nitrite regulation, suggesting that the nasF leader region is involved in nitrate/nitrite regulation. The 119 nucleotide long transcribed leader region contains an apparent factor-independent transcription terminator. Promoter replacement experiments demonstrated that the leader region is involved in nitrate/nitrite regulation of nasF operon expression. Deletions removing the transcription terminator structure resulted in a nitrate-blind constitutive phenotype, indicating that the transcription terminator structure serves a negative function. Other deletions, removing proximal portions of the leader region, resulted in an uninducible phenotype, indicating that this region serves a positive function. These results indicate that nitrate/nitrite regulation of nasF operon expression is determined by a transcription attenuation mechanism. We hypothesize that in the absence of nitrate or nitrite, the terminator structure abrogates transcription readthrough into the nasF operon. In the presence of nitrate or nitrite, the NasR protein mediates transcription antitermination, thereby allowing transcription to proceed into the nasF operon.

Bacterial Proteins↗

A simple, sensitive, non-stimulated photon counting system for detection of superoxide anion in whole blood.

A simple, sensitive, non-stimulated assay was developed to measure the superoxide anion concentration in whole blood, using an ultra-sensitive chemiluminescence (CL) analyzer and lucigenin amplification. The assay system can be performed without leukocyte isolation or stimulant administration. The blood CL levels of healthy males (362.8 +/- 337.7 counts /10 sec) were not different from those of females (335 +/- 308.7 counts/10 sec) (p=0.64), whereas the CL levels in whole blood in patients with acute pancreatitis (2522 +/- 2014 counts/10 sec) were significantly higher than those of healthy controls (p<0.001). This assay system may be valuable in the future for quantitative measurement of reactive oxygen species in various disorders.

Acridines↗

Metabolism of ricinoleate by Neurospora crassa.

Neurospora crassa is a potential expression system for evaluating fatty-acid-modifying genes from plants producing uncommon fatty acids. One such gene encodes the hydroxylase that converts oleate to ricinoleate, a fatty acid with important industrial uses. To develop this expression system, it is critical to evaluate the metabolism and physiological effects of the expected novel fatty acid(s). We therefore examined effects of ricinoleate on lipid biosynthesis and growth of N. crassa. Ricinoleate inhibited growth and reduced levels of phospholipids and 2-hydroxy fatty acids in glycolipids, but led to increased lipid accumulation on a mass basis. To evaluate incorporation and metabolism of ricinoleate, we followed the fate 14 microM-3mM [1-14C]ricinoleate. The fate of the [14C]ricinoleate was concentration-dependent. At higher concentrations, ricinoleate was principally incorporated into triacylglycerols. At lower concentrations, ricinoleate was principally metabolized to other compounds. Thus, N. crassa transformants expressing the hydroxylase gene can be detected if the level of hydroxylase expression allows both growth and ricinoleate accumulation.

Fatty Acids↗

Characterization of oleoyl-12-hydroxylase in castor microsomes using the putative substrate, 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine.

We have characterized the oleoyl-12-hydroxylase in the microsomal fraction of immature castor bean using the putative substrate, 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine (2-oleoyl-PC). Previous characterizations of this enzyme used oleoyl-CoA as substrate and relied on the enzyme transferring oleate from oleoyl-CoA to lysophosphatidylcholine to form 2-oleoyl-PC (acyl-CoA:lysophosphatidylcholine acyltransferase) in addition to oleoyl-12-hydroxylase. The present assay system and characterization use 2-oleoyl-PC as substrate (oleoyl-12-hydroxylase alone). Use of the actual substrate for assay purposes is important for the eventual purification of the oleoyl-12-hydroxylase. Ricinoleate (product of oleoyl-12-hydroxylase) and linoleate (product of oleoyl-12-desaturase) were identified as metabolites of oleate of 2-oleoyl-PC by high-performance liquid chromatography and gas chromatography/mass spectrometry. The activity of oleoyl-12-hydroxylase in the microsomal fraction reached a peak about 44 d after anthesis of castor, while the activity of oleoyl-12-desaturase reached a peak about 23 d after anthesis. The optimal temperature for the oleoyl-12-hydroxylase was about 22.5 degrees C, and the optimal pH was 6.3. Catalase stimulated oleoyl-12-hydroxylase while bovine serum albumin and CoA did not activate oleoyl-12-hydroxylase. The phosphatidylcholine analogue, oleoyloxyethyl phosphocholine, inhibited the activity of oleoyl-12-hydroxylase. These results further support the hypothesis that the actual substrate of oleoyl-12-hydroxylase is 2-oleoyl-PC.

Adenosine Triphosphate↗

Intragenic homozygous deletions of MTS1 gene in gastric cancer in Taiwan.

The multiple tumor suppressor 1 (MTS1) and 2 (MTS2) genes, located on chromosome 9p21, have been reported to be deleted or mutated in many malignant cell lines and in a high percentage of some primary carcinomas. To determine whether these genes are altered, and if so, what is the nature of the alterations, in human gastric adenocarcinoma, we investigated their frequency of mutation by Southern blotting, polymerase chain reaction (PCR) and direct sequencing in 55 patients. Furthermore, loss of heterozygosity (LOH) of chromosome 9p21 at the IFNA locus and D9S171 was assessed. Homozygous deletions of exon 1 of the MTS1 gene were identified in 5 of 55 (9.1%) primary tumors. No deletion of MTS2 gene was noted. LOH was observed in 7 (14.3%) of 49 informative cases (5 cases at IFNA locus, 2 cases at D9S171 and one case with combined LOH at D9S171 and homozygous deletion at exon 1 of MTS1). Direct sequencing of PCR products of the MTS1 and MTS2 gene did not reveal any point mutation in these 55 patients. These data indicate that alterations of the MTS1 and MTS2 genes are infrequently encountered. Additional studies of LOH with more microsatellite markers near 9p21 are mandatory to elucidate whether another tumor suppressor gene exists in the vicinity of MTS1 in primary gastric adenocarcinoma.

Blotting, Southern↗

Aerosolized human neutrophil elastase induces airway constriction and hyperresponsiveness with protection by intravenous pretreatment with half-length secretory leukoprotease inhibitor.

This study was designed to determine the effects of inhaled human neutrophil elastase (HNE) on airway constriction and airway responsiveness, and to examine the protection by an intravenous recombinant half-length secretory leukoprotease inhibitor, r1/2SLPI in guinea pigs. Aerosol inhalation of HNE (250 microgram/ml, for 3 min) caused a transient but significant airway constriction, in which lung resistance (RL) increased from 194 +/- 18 (mean +/- SEM) to 461 +/- 42 cm H2O/L/s (p < 0.001). Thirty minutes after the end of HNE inhalation, airway responsiveness to intravenous 5-hydroxytryptamine (5-HT) was significantly increased. The provocative dose causing a 200% increase in RL (PD200) was significantly decreased from 10.0 +/- 1.2 to 6.5 +/- 0.8 microgram/kg (p < 0.001). Forty-five minutes after the end of HNE inhalation, total cells in bronchoalveolar lavage fluid (BALF) were significantly increased (p < 0.05). Histologic study of intrapulmonary bronchi demonstrated an acute inflammatory response characterized by damage to the epithelium, airway obstruction by mucus plugs, and recruitment of mononuclear and polymorphonuclear cells to the bronchial epithelium. r1/2SLPI (30 mg/kg) injected 5 min before the initiation of HNE inhalation significantly inhibited the airway constriction (p < 0.05), the airway hyperresponsiveness (p < 0.01), and the increase of cells in BALF (p < 0.05). The present data suggest that HNE plays a role in the induction of airway constriction and airway hyperresponsiveness in various inflammatory lung diseases with pulmonary neutrophil infiltration, such as chronic obstructive pulmonary diseases (COPD) and possibly bronchial asthma. r1/2SLPI may be useful as an antiprotease treatment.

Aerosols↗

Erythromycin-induced acute pancreatitis.

BACKGROUND: Pancreatitis due to ingestion of erythromycin is rare. CASE REPORT: A 20-year-old woman took erythromycin 3 g and acetaminophen 6 g before a tooth extraction. Forty minutes later, she experienced severe abdominal pain, nausea, and vomiting. The serum amylase and lipase were elevated. She recovered from the pancreatitis without sequelae after supportive treatment. CONCLUSION: This is the fourth reported case of erythromycin-induced acute pancreatitis in the English literature.

Acute Disease↗

Seroepidemiology of Helicobacter pylori among adolescents in Taiwan.

Helicobacter pylori has been documented to be associated with chronic type B gastritis, peptic ulcer and gastric cancer. In order to examine the seroprevalence and risk factors for Helicobacter pylori infection in Taiwan, a total of 871 adolescents were selected randomly from junior high school children in 20 study precincts and townships. Serum samples collected were tested for IgG antibodies against Helicobacter pylori by enzyme-linked immunosorbent assay using commercial kits. The overall seropositive rate was 21.1% showing no gender difference. There was a striking geographical variation in seroprevalence of Helicobacter pylori infection ranging from 4.6% to 37.1% in 20 precincts and townships. The seroprevalence was highest in the north (25.4%), medium in central Taiwan (21.9%), and lowest in the south (18.7%). The higher the age-adjusted mortality from gastric cancer in a given study area, the higher the seroprevalence of Helicobacter pylori in the area. Metropolitan and aboriginal areas had higher seroprevalences than urban and rural areas, but the difference was not statistically significant. The seroprevalence was higher for those who had no sibling (29.4%) or had a sibship size of > or = 6 (31.1%) than for those with a sibship size of 1-5 (20.0%), but the difference was not statistically significant either.

Adolescent↗

Helicobacter pylori in tumor tissues of patients with advanced gastric adenocarcinoma: high prevalence but failure to detect integration.

Helicobacter pylori has been known to be associated with gastric adenocarcinoma by case control studies. However, significant portion of patients with gastric carcinoma are negative for H. pylori by serological test. To further detect the presence of H. pylori infection in serum and tissue of patients with gastric adenocarcinoma, paired tissues and serum samples from 32 patients with gastric adenocarcinoma were tested. Antibodies to H. pylori were tested by an enzyme linked immunosorbent assay (ELISA) and a Western blot analysis. H. pylori in tumor and non-tumor parts of gastric tissues were examined by histology and polymerase chain reaction (PCR). For serum antibody, eighteen (56%) of these patients were positive by ELISA while 24 (75%) were positive by Western blot. For tissue H. pylori genome, 14 were positive by histology while 28 (87%) were positive by PCR. Southern blot analysis of both tumor and non-tumor tissues revealed no evidence of integration of H. pylori DNA in the human genomes. These results suggest that H. pylori infection can be detected in most patients with gastric adenocarcinoma, and PCR and Western blot can further identify seronegative patients.

Adenocarcinoma↗

Hemosuccus pancreaticus from a splenic artery pseudoaneurysm: an unusual cause of upper gastrointestinal bleeding.

Hemorrhage through the pancreatic duct into the duodenum, so called "hemosuccus pancreaticus", is a rare cause of gastrointestinal bleeding with diagnostic difficulties. We report a 60-year-old man with recurrent upper gastrointestinal bleeding due to rupture of a splenic artery pseudoaneurysm into the pancreatic duct. Initial upper gastrointestinal endoscopy failed to identify the site of the hemorrhage. Abdominal computed tomography disclosed a cystic mass containing a well-enhanced spherical area at the pancreatic tail. Arterial blood flow was demonstrated in the lesion by Doppler ultrasound. Celiac angiography demonstrated a saccular pseudoaneurysm arising from the splenic artery. Bleeding from the ampulla of Vater located in a big duodenal diverticulum was found on repeat endoscopy. Surgical resection of the pseudoaneurysm with distal pancreatectomy and splenectomy was successfully performed. The patient remained symptom-free 5 months after the operation. Hemosuccus pancreaticus, although rare, remains important in the differential diagnosis of upper gastrointestinal bleeding of obscure origin.

Aneurysm, False↗

Low-grade gastric B-cell lymphoma of mucosa-associated lymphoid tissue: clinicopathologic analysis of 19 cases.

Low-grade gastric B-cell lymphoma of mucosa-associated lymphoid tissue type (MALToma) is a recently recognized disease entity. We report the clinicopathologic features of 19 patients with MALToma in Taiwan. The 19 patients included eight men and 11 women, ranging in age from 26 to 77 years, with a mean age of 58.8 years. Most complained of abdominal pain or gastrointestinal bleeding. The endoscopic and gross features of the gastric lesions revealed erosion (flat type), ulceration (depressed type), cobblestone appearance or abnormal gastric folds (elevated type), mimicking chronic gastritis, ulcer or early gastric carcinoma. Typical histopathologic features included lymphoepithelial lesion and extensive mucosal infiltration of centrocyte-like cells in all cases. Clonality analysis of the variable-diversity-joining region of the immunoglobulin gene by semi-nested polymerase chain reaction demonstrated monoclonality in 72% of the cases. Helicobacter pylori bacilli (H. pylori) could be identified on histologic sections in 15 cases (78.9%); the serologic test for H. pylori was positive in 12 of 13 patients tested (92%). In six patients receiving triple therapy (amoxicillin, bismuth subcitrate and metronidazole), five showed significant histologic regression with eradication of H. pylori 4 to 6 months after the start of treatment; one patient showed persistent lesions and presence of H. pylori. However, persistence of residual lymphoid cells and monoclonality of the immunoglobulin gene, could still be demonstrated in four cases. Of nine patients treated with surgery or chemotherapy, two died: one due to concomitant gastric carcinoma and the other one due to sudden apnea. No recurrence was observed in the remaining seven patients. The remaining four patients were lost to follow-up. Our experience confirmed that gastric MALToma is a low-grade neoplastic process. The dramatic response of gastric MALToma to anti-H. pylori treatment suggests that H. pylori infection is closely related to the pathogenesis of low-grade gastric MALToma. However, long-term follow-up is mandatory due to the persistence of the monoclonality of the immunoglobulin gene in the residual lymphoid cells after treatment.

Adult↗

Comparison of the peptide structural requirements for high affinity interaction with bombesin receptors.

Recently it has been established that both a gastrin-releasing peptide (GRP)-preferring bombesin receptor and a neuromedin B-preferring bombesin receptor mediate the mammalian actions of bombesin-related peptides. Because many tissues used for studies of the structure-activity relationship of these peptides possess both receptor subtypes and none possess only the neuromedin B-preferring subtype, there is minimal information on the peptide structural features determining receptor selectivity and it is unknown whether the determinants of agonism at both bombesin receptor subtypes are similar. In the present study we have used native cells either possessing only one bombesin receptor subtype or stably transfected with one subtype to study in detail the peptide structural requirements for interacting and activating each receptor subtype. For the naturally occurring agonists, at the GRP-preferring bombesin receptor the relative affinities were litorin = ranatensin = bombesin > GRP >> neuromedin B, phyllolitorin and at the neuromedin B-preferring bombesin receptor were litorin = neuromedin B = ranatensin > bombesin, phyllolitorin >> GRP. For the GRP-preferring bombesin receptor the heptapeptide and for the neuromedin B-preferring bombesin receptor the octapeptide was the minimal carboxyl fragment interacting with the receptor/or causing biologic activity, and the nonapeptide and full decapeptide, respectively, were the minimal required for full affinity. Making neuromedin B more bombesin- or GRP-like by replacing amino acids in position 3, 6, and 9 demonstrated that position 3 was the most important, followed by position 9 for receptor subtype selectivity. A conformationally restricted GRP analogue, [D-Cys6,D-Ala11,Cys14]bombesin-(6-14) had a significantly higher affinity for GRP-preferring bombesin receptor than NMB receptor. These results demonstrate that: (1) the structure-function relations for the two mammalian bombesin receptors have important differences; (2) suggest that the active conformation of neuromedin B must differ markedly from the beta-sheet model proposed for GRP; and (3) suggest that one important function of the NH2 terminus of GRP and neuromedin B is determining receptor subtype selectivity.

Amino Acid Sequence↗

Occurrence of microsatellite instability in gastric carcinoma is associated with enhanced expression of erbB-2 oncoprotein.

To investigate the molecular mechanism of gastric carcinogenesis, we examined simultaneously the frequency of microsatellite instability and the immunoreactivities to ras, erbB-2, and p53 in 42 gastric adenocarcinoma tissues. Microsatellite instability, measured by DNA replication error, was detected in 33.3% (14/42) of patients with gastric carcinoma while positive immunostaining was demonstrated in 3.1% (1/32) for ras, 40.5% (17/42) for erbB-2, and 28.6% (12/42) for p53. There was no statistical difference between the intestinal type and the diffuse type of carcinoma with respect to microsatellite instability, ras, or erbB-2 expression. The expression of p53 occurred more frequently in the intestinal type of carcinoma (41.7%, 10/24) than in the diffuse type of carcinoma (11.1%, 2/18; P < 0.01). There was no association between microsatellite instability and ras or p53 expression, while enhanced expression of erbB-2 occurred more frequently in carcinomas with microsatellite instability (64.3%, 9/14) than in those without microsatellite instability (28.6%, 8/28; P < 0.05). Such a strong association between microsatellite instability and erbB-2 oncogene may be responsible for the increase of other oncogenic mutations and tumor progression in gastric carcinogenesis.

DNA, Neoplasm↗