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Biomedical subjects

L T Chen

Publications and source records attributed to L T Chen.

At least 19 recordsLinked to original sources

Correct positioning of the venous port-a-cath catheter: comparison of intravascular electrocardiography signal from guidewire and sodium bicarbonate flushed catheter.

A prospective study comparing the efficacy of wire-conducted intravascular ECG (IVECG) signal and signal from the port with a sodium bicarbonate (NaHCO3) flushed catheter to correctly place a catheter tip was carried out in 100 patients. The correct position of the catheter tip was confirmed as follows: with technique G, the IVECG signal was conducted from a guide wire to identify the tip position. With technique P, the IVECG signal was conducted from the port with a NaHCO3 (0.8 mmol/ml) flushed catheter to ascertain the tip position. Each patient received both technique G and technique P in a randomized sequence. The quality of IV-ECG signals, which included baseline drift, P wave pattern and QRS wave pattern, were assessed for ten seconds. Satisfactory quality of these IVECG signals was observed in all of the patients with technique P and 90 of the 100 patients with technique G, and this difference was significant (P=0.001). There was no obvious difference between the techniques in catheter tip placement time or the measured optimal catheter length. The incidence of atrial premature contractions was higher with technique G than with technique P (13% vs 2%; P=0.003). Therefore, technique P is a practical alternative for correctly placing the catheter tip of a Port-A-Cath.

Catheterization, Central Venous↗

In vitro effects of low-intensity ultrasound stimulation on the bone cells.

Mechanical perturbations serve as extracellular signals to a variety of cells, including bone cells. Low-intensity pulsed ultrasound produces significant multifunctional effects that are directly relevant to bone formation and resorption. Ultrasound stimulation has been shown to accelerate bone-defect healing and trabecular bone regeneration. In this study, we use an in vitro bone cell culture model to investigate the effect of low-intensity pulsed ultrasound. The rat alveolar mononuclear cell-calvaria osteoblast coculture system was used in this study. Before treatment, the bone cells were cultured for 3 days to facilitate their attachment and differentiation. Then, ultrasound exposure (frequency = 1 MHz, intensity = 0.068 W/cm(2)) or sham exposure for 20 min per day was applied until the end of the experiment. Half of the culture media were obtained on the 4th, 5th, 6th, 7th, 8th, 9th, and 10th days for the analysis of cytokines and biochemical parameters. At the end of the experiment, cells were fixed and stained for identification and quantification of the osteoblast and osteoclast cells. After low-intensity pulse ultrasound stimulation, the osteoblast cell counts were significantly increased, whereas the osteoclast cell counts were significantly decreased. The total alkaline phosphatase amount in the culture medium was increased after 7 days of ultrasound stimulation, and tumor necrosis factor-alpha in ultrasound-stimulated bone cells was significantly increased after the 7th day of culture and reached 474.77% of the control medium on the 10th day of culture. The results of this study suggest that low-intensity ultrasound treatment may have a stimulatory effect on bone-healing processes.

Acid Phosphatase↗

Prospective study of Helicobacter pylori eradication therapy in stage I(E) high-grade mucosa-associated lymphoid tissue lymphoma of the stomach.

PURPOSE: High-grade mucosa-associated lymphoid tissue (MALT) lymphomas of the stomach are generally believed to be Helicobacter pylori-independent, autonomously growing tumors. However, anecdotal cases of regression of high-grade lymphomas after the cure of H pylori infection had been described. The present prospective study was conducted to evaluate the effect of anti-H pylori therapy in stage I(E) high-grade gastric MALT lymphomas. PATIENTS AND METHODS: Sixteen patients with H pylori infection and stage I(E) gastric high-grade MALT lymphoma consented to a brief antibiotic therapy as first-line treatment from June 1995 through April 2000. Then, patients underwent intensive endoscopic follow-up examinations (+/- endoscopic ultrasonography) with biopsy to evaluate tumor response. Patients with significant improvement of gross lesions that accompanied regression of large cells were followed up without additional treatment. Patients without significant improvement were immediately referred to systemic chemotherapy. RESULTS: Eradication of H pylori was achieved in 15 patients and was accompanied by rapid gross tumor regression and disappearance of large cells in 10. All 10 of these patients with early response had subsequent complete histologic remission of lymphoma. The complete remission rate was 62.5% (95% confidence interval, 35.8% to 89.1%). The response rate was not affected by the tumor grading (proportion of large blast cells within the tumor) but was adversely affected by the depth of tumor invasion. At a median follow-up of 43.5 months (range, 21.1 to 67.4 months), all 10 of these patients remained lymphoma-free. The median duration of complete response was 31.2 months (range, 14.4 to 49.1 months). CONCLUSION: These results suggest that high-grade transformation is not necessarily associated with the loss of H pylori dependence in early-stage MALT lymphomas of the stomach.

Adult↗

Oligomeric interactions between phospholamban molecules regulate Ca-ATPase activity in functionally reconstituted membranes.

Phospholamban (PLB) is a major target of the beta-adrenergic cascade in the heart, and functions as an endogenous inhibitor of Ca-ATPase transport activity. To identify whether oligomeric interactions between PLB molecules are involved in regulating Ca-ATPase transport activity, we have investigated functional interactions between PLB and the Ca-ATPase in proteoliposomes of purified PLB functionally co-reconstituted with the SERCA2a isoform of the Ca-ATPase isolated from cardiac sarcoplasmic reticulum (SR). The calcium sensitivity of this reconstituted preparation and functional stimulation by cAMP-dependent protein kinase (PKA) are virtually identical to those of the Ca-ATPase in cardiac SR microsomes, ensuring the functional relevance of this reconstituted preparation. Interactions between PLB molecules were measured following covalent modification of the single lysine (i.e., Lys(3)) in PLB isolated from cardiac SR membranes with fluorescein isothiocyanate (FITC) prior to co-reconstitution with the Ca-ATPase. FITC modification of PLB does not interfere with the ability of PLB to inhibit the Ca-ATPase, since FITC-PLB co-reconstituted with the Ca-ATPase exhibits a similar calcium dependence of Ca-ATPase activation to that observed in native SR membranes. Thus, the functional arrangement of PLB with the Ca-ATPase is not modified by FITC modification. Using changes in the anisotropy of FITC-PLB resulting from fluorescence resonance energy transfer (FRET) between proximal PLB molecules to measure the average size and spatial arrangement of FITC chromophores, we find that PLB self-associates to form oligomers whose spatial arrangement with respect to one another is in agreement with earlier suggestions that PLB exists predominantly as a homopentamer. The inability of PKA to activate PLB following covalent modification with FITC permits functional interactions between PLB molecules associated with the Ca-ATPase activation to be identified. A second-order loss of Ca-ATPase activation by PKA is observed as a function of the fractional contribution of FITC-PLB, indicating that PKA-dependent activation of two PLB molecules within a quaternary complex containing the Ca-ATPase is necessary for activation of the Ca-ATPase. We suggest that the requirement for activation of two PLB molecules by PKA represents a physiological mechanism to ensure that activation of the Ca-ATPase following beta-adrenergic stimulation in the heart only occurs above a threshold level of PKA activation.

Animals↗

Comparison of MALT and non-MALT primary large cell lymphoma of the stomach: does histologic evidence of MALT affect chemotherapy response?

BACKGROUND: Although the clinicopathologic features of low grade gastric MALToma (lymphoma of mucosa-associated lymphoid tissue) recently have been well delineated, the significance of identifying histologic evidence of MALT origin in a primary high grade gastric lymphoma is less clear. The authors sought to address this issue and, in particular, to clarify if MALT and non-MALT primary large cell gastric lymphoma might have a different response to systemic chemotherapy. METHODS: The authors reviewed the pathologic specimens of all patients who had a diagnosis of primary large cell lymphoma of the stomach and who had been treated primarily by systemic chemotherapy in our institutions January 1, 1988-December 31, 1998. The patients were divided into two groups by experienced hematopathologists, based on the presence or absence of histologic features suggestive of MALToma, including typical lymphoepithelial lesions and infiltration of characteristic centrocyte-like cells. Disease staging was done according to the AJCC/UICC system with Musshoff modification. The median number of gastric biopsies for each patient was 7 (range, 1-21). RESULTS: Seventeen patients with and 26 patients without histologic evidence of MALToma were identified. Clinical features were similar between the two groups except that a greater proportion of patients without evidence of MALToma had elevated levels of serum lactate dehydrogenase (50% vs. 12%, P = 0.01). The median duration of follow-up for the 43 patients was 46.5 months (range, 17-124 mos). All patients received standard systemic chemotherapy including anthracyclines or anthracenedione. The response rate was 88.2% for patients with evidence of MALToma and 57.7% for those without (P = 0.03). The 5-year overall survival rate was 80.5% for patients with evidence of MALToma and 48.9% for those without (P = 0.02). Multivariate analysis indicated that response to chemotherapy, disease stage (Stage I and II-1 vs. Stage II-2, III, and IV), and the presence of MALToma features were independent prognostic factors for overall survival. CONCLUSION: The results of this relatively small study series suggested that the presence of histologic features of MALToma in patients with primary large cell gastric lymphoma might have been associated with a better response to systemic chemotherapy and a better prognosis. Further studies to consolidate this conclusion are necessary.

Adult↗

Evaluation of GL331 in combination with paclitaxel: GL331's interference with paclitaxel-induced cell cycle perturbation and apoptosis.

Combination of selecting agents that act on different cellular mechanisms is a common strategy in cancer chemotherapy. GL331 is a new potent topoisomerase II (Topo II) poison; distinctly, paclitaxel is a microtubule-interfering cancer chemotherapeutic agent. In this study, we intended to evaluate the efficacy of combining GL331 with paclitaxel in cell killing and apoptotic induction in nasopharyngeal carcinoma NPC-TW01 cells. By MTT and internucleosomal DNA cleavage assays, we found that pretreatment or simultaneous treatment of NPC-TW01 cells with GL331 could significantly interfere with paclitaxel's cell killing and apoptosis-inducing activity. When the administration schedule was reversed, the cytotoxicity of GL331 was attenuated by paclitaxel pretreatment. The anti-cancer activity produced by combining GL331 with paclitaxel was obviously lower than the addition of the activities of two individual agents. NPC-TW01 cells were treated with GL331 and 3H-labeled paclitaxel simultaneously or with GL331 before 3H-labeled paclitaxel. In both conditions, GL331 did not reduce the [3H]paclitaxel level in the cells, suggesting that GL331's interference with paclitaxel's cell-killing and apoptosis-inducing efficacy did not result from any inhibition of cellular uptake or retention of paclitaxel. In addition, we found that GL331-induced perturbation of cell cycle progression dramatically over-rode the patterns of mitotic arrest induced by paclitaxel, and the mechanism could be the inhibition of cyclin B1/CDC2 kinase and MAD2 checkprotein activities.

Antineoplastic Agents, Phytogenic↗

Plasma interleukin-1beta, prolactin, ACTH and corticosterone responses to endotoxin after damage of the anterior hypothalamic area.

This report concerns the use of an animal model described by us [J Submicrosc Cytol Pathol 1995;27:83-89] to investigate neural and endocrine sites for endotoxin (ENDO, E. coli 055:B5, 200 microg/100 g body weight in saline intravenously) effects on immunomodulatory hormone and cytokine release. Plasma interleukin-1beta (IL-1beta), prolactin (PRL), ACTH and corticosterone responses to ENDO after neurotoxic damage of neurons residing in the anterior hypothalamic area (AHA) were studied in freely behaving male rats. Excitotoxic cell damage in the AHA was produced by bilaterally injecting N-methyl-DL-aspartate (NMA) in artificial cerebrospinal fluid (aCSF) into this brain site. Injections of comparable volumes of aCSF alone served as controls for brain damage associated with the treatment. In both experimental brain manipulations before ENDO challenge the rise in plasma IL-1beta concentrations in response to ENDO was reduced by 2-fold at 1 h and 3- to 5-fold at 3 h when compared to controls. Nevertheless, experimental and control brain manipulations did not modulate the expected rise in corticosterone concentrations after ENDO exposure which rose 5-fold above the baseline level in all animals. However, AHA manipulation did reduce plasma ACTH and prolactin concentrations differentially. Introduction of either NMA or the control injection of aCSF alone into AHA reduced plasma ACTH concentrations by 2-fold at 0.5 and 1 h after ENDO. However, there was a greater reduction in the rise of plasma PRL concentrations after ENDO found in NMA-treated groups versus rats receiving control aCSF. These results demonstrate that variable-size hypothalamic damage (a larger lesion produced in AHA by NMA treatment vs. a smaller lesion control after aCSF) can result in a differential blunting of PRL, IL-1beta and ACTH release into blood in the face of robust, unmodulated corticosterone increases. In summary, these findings revealed a consistent predominant influence of ENDO on adrenal release of corticosterone as a concomitant to differential IL-1beta, ACTH and PRL release after AHA cell loss. In conclusion, these results constitute further evidence for hypothalamic orchestration of a balance between immunotropic and immunosuppressive neuroendocrine-immune events during acute bacterial infection of mammals.

Adrenocorticotropic Hormone↗

Effect of anti-inflammatory medication on monocyte response to titanium particles.

Cytokines produced by macrophages in the periprosthetic membranes surrounding joint replacements have been implicated as causal agents in osteolysis and prosthetic loosening. The present study characterizes the response of human peripheral blood monocytes to titanium particles. Monocytes were obtained from donated blood and were cultured in the presence of different-sized titanium particles. Exposure to titanium-aluminum-vanadium particles significantly changed the release of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 (IL-1), whereas there was no significant effect on the release of prostaglandin E(2) (PGE(2)). When monocytes were cultured with particles, the titanium alloy particles induced significantly more release of TNF-alpha and less IL-1 secretion. Ciprofloxacin inhibited production of TNF-alpha, IL-6, IL-1, and PGE(2) in human monocytes exposed to titanium particles. In contrast to ciprofloxacin, indomethacin was not a potent inhibitor of TNF-alpha production but potentiated IL-6 production in titanium-stimulated monocytes. Indomethacin had no effect on the production of IL-1 and was a potent inhibitor of PGE(2) production in titanium-stimulated monocytes. Pentoxifylline had an inhibitor effect on TNF-alpha production in titanium-stimulated monocytes. Pentoxifylline potentiated IL-6 and IL-1 production in monocytes exposed to titanium particles and had a biphasic effect on the PGE(2) production. The results of this study support our hypothesis that human monocytes release bone resorption mediators after in vitro exposure to TiAlV alloy particles. The results also demonstrate the differences of bone-resorbing mediators in response to different wear particle size. The pharmacologic agents (ciprofloxacin, pentoxifylline, and indomethacin) that can modulate the release of bone resorbing mediators such as PGE(2), TNF-alpha, IL-1, and IL-6 release from human monocytes. The results help to elucidate the differences in cellular response to wear particles but may not be directly transposed to the human situation.

Anti-Infective Agents↗

Cytokine and adrenal axis responses to endotoxin.

The push-pull cannula (PPC) technique was applied to examine the kinetics of in vivo concentration changes in male rat brain extracellular fluid (ECF) of endogenous interleukin-1beta (IL-1beta) and corticotrophin releasing hormone (CRH) after a peripheral injection of lipopolysaccharide (LPS) (25 microg/100 g b.wt. intravenously). In addition, IL-1beta, adrenocorticotropin hormone (ACTH) and corticosterone concentrations in plasma were also measured at selected intervals after LPS challenge. Administration of LPS resulted in a progressive increase in the concentrations of IL-1beta in brain hypothalamic ECF. A significant increase from the zero time mean value of 77+/-10 to 393+/-88 pg/ml at the 15-min interval was recorded. The increase in IL-1beta concentration in hypothalamic ECF reached a peak of 883+/-237 pg/ml at 30 min post-LPS. CRH concentration in the same hypothalamic ECF was 41+/-17 pg/ml at time zero, 97+/-15 pg/ml at 15 min and at 30 min was significantly increased (215+/-56 pg/ml). A time course of significant increases at 30 min in plasma concentrations of IL-1beta, ACTH and corticosterone was also recorded in the same animals described above. The data show that a peripherally administered LPS bolus elicited an early (over 15 min post-injection) increase in brain ECF IL-1beta concentration; additional significant increases in hormones released from the hypothalamic-pituitary-adrenal (HPA) axis were recorded at 30 min post-LPS injection. These observations support the concept of an early change in hypothalamic ECF concentration of IL-1beta preceding LPS-induced activation of the HPA axis.

Adrenocorticotropic Hormone↗

Chemotherapy alone versus surgery followed by chemotherapy for stage I/IIE large-cell lymphoma of the stomach.

The optimal treatment of localized large-cell lymphoma of the stomach remains controversial. In particular, the role of surgical resection of the primary tumor needs to be clearly defined. We have reviewed all patients with a diagnosis of gastric lymphoma and treated in our institutions between 1988 and 1998. Patients fulfilling the following criteria were included in this study: (1) histologically proven large-cell lymphoma of the stomach; (2) adequate pathological materials and complete clinical information for analysis; (3) clinical stage I/II disease according to the Musshoff modification of Ann Arbor system; and (4) received primary chemotherapy alone with anthracycline- or anthracenedione-containing regimens (group A) or curative surgery followed by adjuvant chemotherapy (group B). There were 38 and 21 patients in group A and group B, respectively. All pertinent clinicopathologic features were similar between the two groups of patients, except that patients of group A had significantly more stage II-2 disease (P = 0.004). Of group A, among 36 patients who could be evaluated for response to chemotherapy, there were 29 complete and 1 partial responses, with an overall response rate of 83.3% (95% CI, 71.1-95.5%). The projected 5-year relapse-free survival (RFS) and overall survival (OS) were 86.0% (95% CI, 73.3-98.7%) and 72.6% (95% CI, 57.0-88.2%), respectively. On the other hand, the projected 5-year RFS and OS of group B were 77.9% (95% CI, 58.0-97.8%) and 77.8% (95% CI, 57.9-97. 7%), respectively, not significantly different from that of group A. Our data suggest that systemic chemotherapy alone may be a reasonable alternative treatment for stage I/II large-cell lymphoma of the stomach. Resection of the primary tumor before systemic chemotherapy does not appear to improve the cure rate of this group of patients.

Adult↗

In vitro evaluation of GL331's cancer cell killing and apoptosis-inducing activity in combination with other chemotherapeutic agents.

GL331 is a novel podophyllotoxin-derived compound and is more efficacious than its congener VP-16 in killing several types of cancer cells, that has promoted considerable interest in its possibility of clinical use. In this study, we found that the higher cytotoxicity of GL331 in nasopharyngeal carcinoma NPC-TW01 cells was attributed to the elevated ability to induce apoptotic cell death. In addition to evaluation of GL331's single agent activity, the use of GL331 in combination with other established therapeutic agents was also evaluated. We found that GL331-induced cell cycle perturbation occurred upon initial 8-h exposure, and pretreatment of NPC-TW01 cells with GL331 for 8 h significantly interfered with the cytotoxicities of VP-16, cisplatin, 5-fluorouracil and adriamycin. When the schedule of drug administration was reversed, high-toxic concentrations of these agents revealed an antagonistic effect on GL331; however, their low-toxic doses had the additive or even more-than-additive effect on the cytotoxicity induced by GL331 at 0.1 microM or less, but for GL331 concentrations of greater than 1 microM, the effect became less than additive. These data suggest that overlapping mechanisms could be elicited by GL331 and other agents, and additional preclinical studies are needed to determine the optimal dose combination and administration schedule that will enhance, rather than interfere with, the efficacy of GL331 in combination with other anti-cancer agents.

Antineoplastic Agents, Phytogenic↗

The association between Helicobacter pylori infection and functional dyspepsia in patients with irritable bowel syndrome.

OBJECTIVE: Irritable bowel syndrome (IBS) is associated with an exaggerated response to a variety of physiological and nonphysiological gastrointestinal stimuli. Many patients with IBS also have functional dyspepsia. Our aim was to examine the hypothesis that Helicobacter pylori (H. pylori) infection may predispose IBS patients to functional dyspepsia. METHODS: In 69 IBS patients, dyspeptic symptoms, H. pylori status, and sociodemographic and psychological variables (perceived stress, trait anxiety, and depression) were assessed. Sociodemographic and psychological variables were also evaluated in 52 control subjects. RESULTS: Mean scores for perceived stress (17.1 +/- 6.0 vs 14.9 +/- 6.0, p = 0.05), trait anxiety (45.6 +/- 9.1 vs 41.1 +/- 7.8, p = 0.004) and depression (9.9 +/- 8.4 vs 5.0 +/- 5.5, p = 0.0002) were higher in IBS patients than in controls. In all, 33 of the 69 patients (47.8%) had H. pylori infection, and this was associated with relevant symptoms of epigastric pain (odds ratio [OR] = 6.77, 95% confidence interval [CI] 1.89-24.3) and postprandial upper abdominal fullness (OR = 4.23, 95% CI 1.38-13.2). H. pylori infection and female gender were independent predictors of the presence of relevant dyspepsia (OR = 8.31, 95% CI 2.35-29.5 and 6.06, 95% CI 1.71-21.5, respectively). Symptom intensity was associated with the level of perceived stress (total relevant symptom number > or =3 vs <3, OR = 1.16 per point on a 40-point perceived stress scale, 95% CI 1.01-1.34). CONCLUSIONS: In IBS patients, the presence of dyspepsia is associated with H. pylori infection, female gender, and perceived stress.

Adult↗

Simplified 13C-urea breath test for the diagnosis of Helicobacter pylori infection--the availability of without fasting and without test meal.

The conventional 13C-urea breath test (13C-UBT) for detecting Helicobacter pylori infection was performed during fasting state and with a test meal to delay gastric emptying during the test. For the convenience of propagating this test, we assessed the availability of non-fast and without test meal in 13C-UBT for the diagnosis of H. pylori infection. One hundred and five consecutive patients who received endoscopic examination were studied. All of them received endoscopic biopsy for urease test, culture and histopathology to determine whether there was a presence of H. pylori infection. Each patient received four separate 13C-UBT under the following four testing conditions. Test I) fasting state with test meal (100 ml fresh milk), Test II) non-fast (taking usual food) but with test meal, Test III) fasting state without test meal, and Test IV) non-fast and without test meal. The excess delta 13CO2 values were calculated via the breathed samples that were collected at 15 minutes after ingestion of 13C-urea. There were 61 H. pylori positive and 44 negative patients in this study, with an excess delta 13CO2 values 3.0, 4.0, 3.5 and 4.0 as a cut-off value in the four tests respectively, according to the ROC curve. The results of test I, a conventional procedure, had a good correlation with the gold standard. The sensitivity and specificity were 100% and 95% respectively. The alternative procedures in other tests also have high sensitivity and specificity at 15-minute detecting time. The sensitivity of the tests II, III and IV at 15-minute detecting times were 98%, 98% and 100%, and the specificities of those were 95%, 98% and 95% respectively. We therefore suggest that fasting and test meal possibly be omitted when the cut-off value is 4.0 per mil in the simplified 13C-UBT (non-fast and without test meal, and detection at 15 minutes after ingestion of 13C-urea) which is a simple and available procedure for clinical diagnosis of H. pylori infection.

Adult↗

A candidate target for G protein action in brain.

An effector candidate for G protein action, GRIN1, was identified by screening a cDNA expression library with phosphorylated GTPgammaS-G(z)alpha as a probe. GRIN1 is a novel protein without substantial homology to known protein domains. It is expressed largely in brain and binds specifically to activated G(z)alpha, G(o)alpha, and G(i)alpha through its carboxyl-terminal region. The protein KIAA0514 (GRIN2) is homologous to GRIN1 at its carboxyl terminus and also binds to activated G(o)alpha. Both GRIN1 and G(o)alpha are membrane-bound proteins that are enriched in the growth cones of neurites. Coexpression of GRIN1 or GRIN2 with activated G(o)alpha causes formation of a network of fine processes in Neuro2a cells, suggesting that these pathways may function downstream of G(o)alpha to control growth of neurites.

Adaptor Proteins, Signal Transducing↗

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↗

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↗

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↗