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Biomedical subjects

L T Chen

Publications and source records attributed to L T Chen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Isolation of a Helicobacter pylori protein, FldA, associated with mucosa-associated lymphoid tissue lymphoma of the stomach.

BACKGROUND & AIMS: The growth of gastric mucosa-associated lymphoid tissue lymphoma (MALToma) seems to depend on the stimulation of Helicobacter pylori. We attempted to identify specific antigen(s) from H. pylori strains associated with MALToma. METHODS: Membranous and secreted proteins of H. pylori were compared on sodium dodecyl sulfate-polyacrylamide gel electrophoresis by Western blot using sera from patients with MALToma. RESULTS: A 19-kilodalton protein was seen in all strains isolated from patients with MALToma but uncommonly in other strains. The protein was purified and sequenced. Amino acid sequence comparison showed it was an FldA homologue, a putative flavodoxin protein. DNA sequencing in 26 strains revealed that a nucleotide G insertion at position 481 of the fldA gene was more frequently observed in strains associated with MALToma than other strains (9/9 vs. 6/17; P = 0.002). The mutation caused a short truncation. A recombinant protein with this truncation was expressed and tested. Sera of 12 (70.6%) of 17 patients with MALToma were positive for the antibody to the recombinant protein, and 7 (16.7%) of 42 control patients were positive (12/17 vs. 7/42; P < 0.0001). CONCLUSIONS: Truncated FldA of H. pylori is associated with gastric MALToma. It may be involved in the pathogenesis of gastric MALToma. Antibody to this antigen could be used as a serological marker of the disease.

Adult↗
PubMed1999

Lung cancer mimicking acute myocardial infarction on electrocardiogram.

Myocardial involvement by malignant neoplasm is rare and often not clinically manifested. The diagnosis is usually made only at autopsy. A 71-year-old man with squamous cell lung cancer presented with chest discomfort. His electrocardiogram was diagnostic of acute myocardial infarction. However, because of the lack of classic symptoms and signs of acute myocardial infarction and normal serum levels of cardiac enzymes, an echocardiography was performed before initiation of thrombolytic therapy. The echocardiography showed a huge hyperechoic mass located in the posterolateral aspect of the left ventricle with myocardium invasion. Thrombolytic therapy was withheld. In patients with lung cancer, an electrocardiogram representative of acute myocardial infarction can rarely be induced by myocardial involvement with lung cancer.

Aged↗
PubMed1999

A novel podophyllotoxin-derived compound GL331 is more potent than its congener VP-16 in killing refractory cancer cells.

PURPOSE: GL331 is a new homolog of VP-16, and has demonstrated more efficacious anti-cancer activity in both the in vitro and in vivo lymphoma systems. To extensively explore GL331's clinical value, we furthermore evaluate the cytotoxicity and apoptosis-inducing activity of GL331 in several human cell lines from cancers that are not normally treated with VP-16. METHODS: By MTT and clonogenic survival assays, the cytotoxicities of GL331 and VP-16 were evaluated in a variety of cell lines including nasopharyngeal, hepatocellular, gastric, colon, cervical, and neuroblastoma cancer types. Western blot analysis was performed to detect the MDR-1 level in these cell lines. By Annexin V-staining flow cytometry and detection of DNA ladders, the apoptosis-inducing activities of GL331 and VP-16 were also evaluated. RESULTS: GL331 showed more efficacy than its congener VP-16 in killing cancer cells. The estimated ID50 of GL331 were 2.5 to 17-fold lowerthan those of VP-16. GL331 possessed more cell-killing activity even in MDR-1-overexpressing cell lines such as HCC36 and SW620. Its higher cytotoxicity could be attributed by the elevated ability to induce apoptotic cell death. CONCLUSION: GL331's overriding drug resistance and higher cancer cell-killing activity suggest its superiority in clinical cancer therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

The status of the do-not-resuscitate order in Chinese clinical trial patients in a cancer centre.

OBJECTIVE: To report and analyse the pattern of end-of-life decision making for terminal Chinese cancer patients. DESIGN: Retrospective descriptive study. SETTING: A cancer clinical trials unit in a large teaching hospital. PATIENTS: From April 1992 to August 1997, 177 consecutive deaths of cancer clinical trial patients were studied. MAIN MEASUREMENT: Basic demographic data, patient status at the time of signing a DNR consent, or at the moment of returning home to die are documented, and circumstances surrounding these events evaluated. RESULTS: DNR orders were written for 64.4% of patients. Patients in pain (odds ratio 0.45, 95% CI 0.22-0.89), especially if requiring opioid analgesia (odds ratio 0.40, 95% CI 0.21-0.77), were factors associated with a higher probability of such an order. Thirty-five patients were taken home to die, a more likely occurrence if the patient was over 75 years (odds ratio 0.12, 95% CI 0.04-0.34), had children (odds ratio 0.14, 95% CI 0.02-0.79), had Taiwanese as a first language (odds ratio 6.74, 95% CI 3.04-14.93), or was unable to intake orally (odds ratio 2.73, 95% CI 1.26-5.92). CPR was performed in 30 patients, none survived to discharge. CONCLUSIONS: DNR orders are instituted in a large proportion of dying Chinese cancer patients in a cancer centre, however, the order is seldom signed by the patient personally. This study also illustrates that as many as 20% of dying patients are taken home to die, in accordance with local custom.

Adult↗
PubMed1998

Affinity purification of the Ca-ATPase from cardiac sarcoplasmic reticulum membranes.

We report the isolation of the functional form of the Ca-ATPase from porcine cardiac sarcoplasmic reticulum (SR) membranes, taking advantage of the ability of this enzyme to bind to the nucleotide site affinity dye, Reactive Red 120. Conditions that optimize the solubility and functional stability of the cardiac Ca-ATPase in detergent during the purification procedure are essential to its recovery. The purified Ca-ATPase migrates as a single band on Coomassie blue-stained polyacrylamide gels and exhibits high specific activity (2.5 IU at 25 degreesC) and functional stability. Similar enrichment of the Ca-ATPase estimated from either relative amounts of the 100-kDa protein band on polyacrylamide gels or steady-state concentrations of phosphorylated enzyme intermediate (E-P) demonstrate that neither nonfunctional Ca-ATPases nor non-Ca-ATPase proteins migrating with an apparent molecular weight of 100 kDa constitute a significant fraction of these preparations. Steady-state levels of E-P are 1.3 and 8.6 nmol/mg protein, respectively, for native cardiac SR membranes and the final purified fraction. These values, in comparison to the maximum value (9.1 nmol/mg) for the 110-kDa protein, agree well with estimates of total Ca-ATPase abundance from gel densitometry for both preparations and indicate full site reactivity, i.e., one phosphorylation site for each 110-kDa cardiac Ca-ATPase polypeptide chain.

Animals↗
PubMed1998

Quantification of Helicobacter pylori infection: Simple and rapid 13C-urea breath test in Taiwan.

The 13C-urea breath test (13C-UBT) is a non-invasive method for detecting Helicobacter pylori. This study was performed to determine the cutoff value and evaluate the sensitivity and specificity of 13C-UBT in Taiwan. 13C-Urea (100 mg of 99% 13C-labeled urea) was dissolved in 50 ml sterile water for the test. The test meal for delaying gastric emptying was 100 ml fresh milk. Patients fasted for at least 6h. A baseline breath sample was collected 5 min after they had the test meal. Two other samples were collected at 15 and 30 min after the patients ingested the 13C-urea. The test was evaluated in 352 patients after routine upper gastrointestinal endoscopy, and the urease test, culture, and histopathology were taken as the gold standards for detecting H. pylori. According to the receiver operating characteristic (ROC) curves, we chose values of 2.8 and 4.2 excess delta 13CO2 per mil as the cut-off values for 15 and 30 min, respectively, post 13C-urea. The sensitivity and specificity of 13C-UBT were 99% and 93% at 15 min, and 98% and 93% at 30 min post 13C-urea, respectively. The 13C-UBT breath test is an efficient non-invasive method of high sensitivity and high specificity for detecting H. pylori infection. We suggest that the use of fresh milk as the test meal and the detection of excess delta 13CO2 15 min after the ingestion of 13C-urea are suitable for the clinical use of 13C-UBT. This test is simple and rapid.

Adolescent↗
PubMed1998

Continuous infusion cisplatin and etoposide chemotherapy for cancer of unknown primary site (CUPS) in Taiwan, a region with a high prevalence of endemic viral infections.

BACKGROUND: To evaluate the efficacy and toxicity of cisplatin/etoposide continuous infusion chemotherapy for cancer of unknown primary site in Taiwan, a region with a high prevalence of endemic viral infections. METHOD: Between April 1994 and February 1996, 20 patients with a diagnosis of CUPS were treated, including 15 males and five females, of average age 63.3 years (range 41-83 years). Continuous intravenous infusion of etoposide 80 mg/m2 and cisplatin 25 mg/m2 was given for 3 days every 3 weeks. Pretreatment tumor marker and viral serology studies were performed for baseline evaluation. Nearly two-thirds of the patients had poorly differentiated carcinoma. The average number of metastatic sites was 2.65 (range 1-4), with liver and lymph node involvement predominating. RESULTS: The overall response rate was 25% (95% CI 17.7-32.3%); 30.7% for poorly differentiated cancers and 25% for well differentiated cancers. Median survival was 4 months (range 1-12 months), 4.8 months for patients attaining partial response. Toxicity was moderate, grade 3 and 4 neutropenia occurred in 55% and grade 3 and 4 thrombocytopenia in 40%; other toxicities were mild. CA125 and CA199 were elevated in more than 50% of patients. Viral serology studies were not significantly different from those of the indigenous population. CONCLUSION: Etoposide and cisplatin combination chemotherapy has modest activity in patients with extensive CUPS and, at the schedule and dosage given, it is associated with moderate toxicity.

Adult↗
PubMed1998

Maternal diet fatty acid composition affects neurodevelopment in rat pups.

The effect of pre- and postnatal maternal dietary fatty acid composition on neurodevelopment in rat pups was studied. Timed pregnant dams were fed, beginning on d 2 of gestation and throughout lactation, either nonpurified diet (reference) or a purified diet whose fat source (22% of energy) was either corn oil or menhaden fish oil. On postnatal d 3, pups were randomly cross-fostered among dams of the same diet group and culled to 10 pups per dam. Milk was removed from stomachs of culled pups for fatty acid analyses. From postnatal d 4 to 30, pups were assessed daily for the appearance of neurodevelopmental reflexes. Auditory brainstem conduction times were measured on postnatal d 23 and 29. Pups were killed on postnatal d 30, and cerebrums were removed for fatty acid analyses. The fatty acid composition of maternal milk and pup cerebrums reflected maternal diet with higher levels of (n-3) and (n-6) fatty acids in the fish oil and corn oil groups, respectively. The time of appearance of auditory startle was significantly delayed (P = 0.004), and auditory brainstem conduction times on postnatal d 23 and 29 were significantly longer in pups of the fish oil- than corn oil-fed dams (P </= 0.05). A delay in the appearance of the auditory startle reflex and longer auditory brainstem conduction times in pups of dams fed fish oil-supplemented diet may be due to negative effects on myelination of the auditory brainstem pathway.

Animals↗
PubMed1998

Remarkable destabilization of recombinant alpha-lactalbumin by an extraneous N-terminal methionyl residue.

A recombinant bovine alpha-lactalbumin, possessing an additional N-terminal methionyl residue, was expressed in Escherichia coli. In order to address the effects of the N-terminal methionyl residue on conformational stability, the thermal stability of the recombinant alpha-lactalbumin was investigated by measuring temperature-dependence of circular dichroism spectra, and it was compared with that of authentic alpha-lactalbumin from bovine milk. The thermal stability of the recombinant alpha-lactalbumin was significantly lower than that of authentic alpha-lactalbumin. The enthalpy change of unfolding of the recombinant protein was found to be the same as that of the authentic one when compared at the same temperature. Therefore, the N-terminal methionyl residue seems to destabilize the conformation of recombinant alpha-lactalbumin through some entropic effects.

Animals↗
PubMed1997

Menadione-induced cytotoxicity to rat osteoblasts.

Oxygen-derived free radical injury has been associated with several cytopathic conditions. Oxygen radicals produced by chondrocytes is an important mechanism by which chondrocytes induce matrix degradation. In the present study, we extend these observations by studying oxidative processes against osteoblasts. Osteoblasts were mixed in in vitro culture with 200 microM menadione. The cytotoxic effect of menadione-induced oxidative stress was monitored by lucigenin- or luminol-amplified chemiluminescence, tetrazolium assay and immunocytochemical study. Results showed that adding menadione induces an oxidative stress on osteoblasts, via superoxide and hydrogen peroxide production, that can be eradicated by superoxide dismutase (SOD) and catalase in a dose-dependent manner. Catalase and the appropriate concentration of dimethyl sulfoxide have a protective effect on cytotoxicity induced by menadione, whereas SOD does not. Menadione-treated osteoblasts have a strong affinity for annexin V, and the nuclei are strongly stained by TUNEL (TdT-mediated dUTP nick-end labelling). The results suggest that menadione-triggered production of reactive oxygen species leads to apoptosis of osteoblasts.

Acridines↗
PubMed1997

Organization of G proteins and adenylyl cyclase at the plasma membrane.

There is mounting evidence for the organization and compartmentation of signaling molecules at the plasma membrane. We find that hormone-sensitive adenylyl cyclase activity is enriched in a subset of regulatory G protein-containing fractions of the plasma membrane. These subfractions resemble, in low buoyant density, structures of the plasma membrane termed caveolae. Immunofluorescence experiments revealed a punctate pattern of G protein alpha and beta subunits, consistent with concentration of these proteins at distinct sites on the plasma membrane. Partial coincidence of localization of G protein alpha subunits with caveolin (a marker for caveolae) was observed by double immunofluorescence. Results of immunogold electron microscopy suggest that some G protein is associated with invaginated caveolae, but most of the protein resides in irregular structures of the plasma membrane that could not be identified morphologically. Because regulated adenylyl cyclase activity is present in low-density subfractions of plasma membrane from a cell type (S49 lymphoma) that does not express caveolin, this protein is not required for organization of the adenylyl cyclase system. The data suggest that hormone-sensitive adenylyl cyclase systems are localized in a specialized subdomain of the plasma membrane that may optimize the efficiency and fidelity of signal transduction.

Adenylyl Cyclases↗
PubMed1997

Mitomycin-C induced hemolytic uremic syndrome: a case report and literature review.

Hemolytic uremic syndrome spontaneously arises in a few patients with advanced cancer, but it is more commonly related to the use of certain chemotherapeutic agents. Mitomycin-C is, etiologically, the most common causative agent inducing hemolytic uremic syndrome, in a dose dependent manner. We report this syndrome, attributable to mitomycin-C at a cumulative dose of 40 mg/m2, in a gastric cancer patient. A 42-year-old female with stage III gastric cancer underwent radical gastrectomy and was given mitomycin-C at 10 mg/m2 intravenously every four weeks as adjuvant therapy. Hemolytic uremic syndrome was diagnosed three months after the last dose of mitomycin-C administration. The most prominent symptoms included pallor, hypertension and anasarca, with laboratory evidence of microangiopathic hemolytic anemia, azotemia and hyperkalemia. Her disease was progressive, but fortunately stabilized after staphylococcus column A dialysis. Her disease remained in remission for 24 months from the time of diagnosis, and then relapsed in the form of peritoneal carcinomatosis with partial intestinal obstruction.

Adenocarcinoma↗
PubMed1997

The fatty acid composition of maternal diet affects lung prostaglandin E2 levels and survival from group B streptococcal sepsis in neonatal rat pups.

Dietary fatty acid effects upon the immune system may be mediated in part by effects upon the synthesis of proinflammatory mediators. The effects of maternal dietary fatty acid composition upon lung prostaglandin (PG) E2 levels and survival from group B streptococcal (GBS) infection were investigated in neonatal rat pups. Beginning on d 2 of gestation and throughout lactation, pregnant dams were fed a purified diet whose fat source (22% of energy) was either corn oil or menhaden fish oil. On postnatal d 3, pups were randomly cross-fostered to dams of the same diet group to minimize litter effects; litters were then culled to 10 pups per dam. On postnatal d 7, pups were either injected with 1 x 10(7.5) GBS organisms or were killed for determination of lung tissue levels of PGE2 and lung and erythrocyte fatty acid composition. Arachidonic acid and PGE2 levels were significantly higher in the lungs of pups in the corn oil group compared with the fish oil group. Forty-nine percent of pups in the corn oil group survived the GBS challenge compared with 79% of pups in the fish oil group (P = 0.0005). These data suggest that the fatty acid composition of pre- and/or postnatal diet affects the neonatal response to immune challenge, which may be due in part to effects upon the synthesis of pro-inflammatory mediators.

Animals↗
PubMed1997

Comparison of intravenous granisetron with metoclopramide plus dexamethasone in the prevention of nausea and vomiting associated with emetogenic cytotoxic chemotherapy.

Fifty-one patients who received their first course of chemotherapy were studied to compare the respective efficacy and safety of granisetron and metoclopramide plus dexamethasone in the prevention of nausea and vomiting induced by emetogenic cytotoxic drugs. The results showed the response rate of antiemesis in the first 24 hours was higher in the metoclopramide plus dexamethasone group than in the granisetron group: 95% vs 84%. For the next six days of the study period, the response rate of the granisetron group was shown to be more effective than that of metoclopramide plus dexamethasone group: 77% vs 60%. Furthermore, the granisetron seemed to display enhanced tolerability with less drug-related side effects and no extrapyramidal effects which appeared in 2 cases of the metoclopramide plus dexamethasone group. In conclusion, a single dose of granisetron can be as effective as the gold standard of metoclopramide plus dexamethasone regimen in preventing and treating acute nausea and vomiting. For preventing delayed nausea and vomiting, granisetron is shown to be more effective than metoclopramide plus dexamethasone.

Adult↗
PubMed1996

Phosphorylation of phospholamban by cAMP-dependent protein kinase enhances interactions between Ca-ATPase polypeptide chains in cardiac sarcoplasmic reticulum membranes.

We have used spin-label EPR spectroscopy to examine possible alterations in protein-protein interactions that accompany the activation of the cardiac sarcoplasmic reticulum (SR) Ca-ATPase following the phosphorylation of phospholamban (PLB). Using a radioactive derivative of a maleimide spin label (MSL), we have developed conditions for the selective spin-labeling of the Ca-ATPase in both native cardiac and skeletal sarcoplasmic reticulum membranes. The rotational dynamics of the cardiac and skeletal Ca-ATPase isoforms in native SR membranes were measured using saturation transfer EPR. We report that the phosphorylation of PLB in cardiac SR results in a (1.8 +/- 0.2)-fold reduction in the overall rotational mobility of the Ca-ATPase. The alteration in the rotational dynamics of the Ca-ATPase is the direct result of the phosphorylation of PLB, and is not related to the phosphorylation of the Ca-ATPase or any other SR proteins since no alteration in the ST-EPR spectrum is observed as a result of conditions that phosphorylate the cardiac Ca-ATPase with ATP. Neither do the use of conditions that activate the Ca-ATPase in cardiac SR result in the alteration of the rotational dynamics or catalytic properties of the Ca-ATPase in skeletal SR where PLB is not expressed. Measurements of the rotational dynamics of stearic acid spin labels (SASL) incorporated into cardiac SR membranes with a nitroxide at the 5- and 12-positions using conventional EPR indicate that there is virtually no difference in the lipid acyl chain dynamics in cardiac SR membranes upon the phosphorylation of PLB. These results indicate that the decrease in the rotational dynamics of the Ca-ATPase in cardiac SR membranes associated with the phosphorylation of PLB is related to enhanced interactions between individual Ca-ATPase polypeptide chains due to (i) an alteration in the spatial arrangement of cardiac Ca-ATPase polypeptide chains within a defined oligomeric state or (ii) increased protein-protein associations. We suggest that altered interactions between Ca-ATPase polypeptide chains and PLB serves to modulate the activation barrier associated with calcium activation of the Ca-ATPase in cardiac SR membranes.

Animals↗
PubMed1996

High seroprevalence of IgG against Helicobacter pylori among endoscopists in Taiwan.

A prospective survey to investigate the seroprevalence of IgG against Helicobacter pylori among endoscopists in Taiwan was conducted by analyzing blood samples of 70 study subjects and 64 nonendoscopist physicians with quantitative ELISA. Personal information and the practices of infection control related to gastroscopy examination were obtained by a self-administered questionnaire. Significant differences were detected in the IgG prevalence between study and control subjects (80.0% vs 51.6%; P < 0.05). The serum level of antibody in endoscopists (385.2 +/- 36.1 unit/ml) was significantly higher than that of nonedoscopists (211.8 +/- 33.0 unit/ml; P = 0.018). Endoscopists performing 30 or more sessions of gastroscopy per week had higher seroprevalence than those performing less than 30 sessions (90.9% vs 70.3%; P = 0.0126). In conclusion, endoscopists in Taiwan had a high prevalence of H. pylori infection. The cause might be related to the frequency of gastroscopies performed.

Adult↗
PubMed1996

Plasma and erythrocyte thiamin concentrations in geriatric outpatients.

OBJECTIVE: The objective of this study was a) to determine the plasma and red cell thiamin levels in geriatric outpatients and b) to evaluate, using the rat model, the sensitivity of plasma thiamin concentration as an indicator of nutritional status for this vitamin. SUBJECTS: Thirty geriatric outpatients were evaluated for their plasma and erythrocyte thiamin levels. METHODS: Plasma and red cell thiamin levels were determined by a microbiologic assay using kloeckera apiculata. Sprague-Dawley rats were fed a thiamin deficient diet. Blood samples were obtained on specified days and the plasma and erythrocyte thiamin levels determined. RESULTS: Forty-three percent of the subjects studied had plasma thiamin levels below 2 SD of the mean of the younger-age group (20-60 yr) while 57% had a plasma thiamin below 10 ng/ml (the lower reference range of the younger age group). Twenty-seven percent were found to have red cell thiamin levels below 2 SD of the mean of the younger-age group, while 33% had red cell thiamin levels below 138 ng/ml (the lower reference range of the younger-age group). The rat study indicated that plasma thiamin concentration is a sensitive indicator of the nutritional status for this vitamin. CONCLUSION: About 50% of geriatric outpatients in this study had low plasma thiamin levels. The long-term effect of a low plasma thiamin level on cognitive functions remains to be investigated.

Adult↗