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Biomedical subjects

M Chu

Publications and source records attributed to M Chu.

At least 55 records · Page 3Linked to original sources
PubMed1996

The basic domain/leucine zipper protein hXBP-1 preferentially binds to and transactivates CRE-like sequences containing an ACGT core.

The transcription factor hXBP-1 belongs to the family of basic region/leucine zipper (bZIP) proteins and interacts with the cAMP responsive element (CRE) of the major histocompatibility complex (MHC) class II A alpha, DR alpha and DP beta genes. However, the developmental expression of hXBP-1 as revealed by in situ hybridization in mouse embryos, has suggested that it interacts with the promoter of additional genes. To identify other potential target genes of this factor, we performed binding site selection experiments with recombinant hXBP-1 protein. The results indicated that hXBP-1 binds preferably to the CRE-like element GAT-GACGTG(T/G)NNN(A/T)T, wherein the core sequence ACGT is highly conserved, and that it also binds to some TPA response elements (TRE). hXBP-1 can transactivate multimers of the target sequences to which it binds in COS cells, and the level of transactivation directly correlates with the extent of binding as observed in gel retardation experiments. One target sequence that is strongly bound by hXBP-1 is the 21 bp repeat in the HTLV-1 LTR, and we demonstrate here that hXBP-1 can transactivate the HTLV-1 LTR. Further, the transactivation domain of hXBP-1 encompasses a large C-terminal region of the protein, containing domains rich in glutamine, serine and threonine, and proline and glutamine residues, as shown in transient transfection experiments using hXBP-1-GAL4 fusion proteins and a reporter gene under the control of GAL4-binding sites.

Animals↗
PubMed1996

The national distribution of Certified Registered Nurse Anesthetists across metropolitan and nonmetropolitan settings.

The purpose of this study is to describe the metropolitan and nonmetropolitan distribution of Certified Registered Nurse Anesthetists actively practicing across the United States. More than 3,000 counties of the United States were categorized according to degree of urbanization by utilizing the rural-urban continuum codes for metropolitan and nonmetropolitan counties developed within the U.S. Department of Agriculture. Zip code information was used to locate all actively practicing CRNAs by county of residence. Applying the rural-urban continuum codes to this database revealed a descriptive national distribution of CRNAs across geographical areas. Data show that 81.3% (18,086) of CRNAs reside in metropolitan counties and that 18.7% (4,182) reside in nonmetropolitan areas. The greatest number of CRNAs (8,519) are found in central counties of metropolitan areas of one million population or more. The lowest number of CRNAs (90) are found in completely rural counties of fewer than 2,500 urban population adjacent to a metropolitan area, and 160 CRNAs reside in counties of fewer than 2,500 population not adjacent to a metropolitan area. Differences in age, gender distribution, educational credentials, and population ratios are also noted between metropolitan and nonmetropolitan CRNAs.

Adult↗
PubMed1995

Effect of endogenous hypergastrinemia on gastrin receptor expressing human colon carcinoma transplanted to athymic rats.

BACKGROUND & AIMS: The effect of endogenous hypergastrinemia on growth of human colon carcinoma is not known. Our aim was to study the growth of human colon carcinoma in an animal model with endogenous hypergastrinemia. METHODS: Human colon carcinoma was transplanted to the colon of 40 athymic rats. Of these, 25 underwent gastric fundectomy to accomplish endogenous hypergastrinemia, and 15 were sham operated to serve as controls. The duration of the study was 8 weeks. During the last week, 12 fundectomized animals received a gastrin (cholecystokinin B) receptor antagonist. Metaphase arrest index, local invasion, and distant spread of the tumor were investigated. Expression of gastrin and cholecystokinin B receptor messenger RNA was examined by reverse-transcription polymerase chain reaction. RESULTS: Tumor spread by direct extension outside the colon was observed in all animals, and liver metastases were observed in 10 of the 25 fundectomized animals. Sham-operated animals showed none of these features. The metaphase arrest index of the tumor did not differ between fundectomized animals given the cholecystokinin B receptor antagonist and sham-operated animals, whereas it was significantly increased in fundectomized animals not given the antagonist. The tumor expressed both gastrin and cholecystokinin B receptor messenger RNA. CONCLUSIONS: The results indicate that endogenous hypergastrinemia may promote proliferation and spread of human colon carcinoma expressing cholecystokinin B receptor.

Aged↗
PubMed1995

Mutational analysis of the coat protein N-terminal amino acids involved in potyvirus transmission by aphids.

The nature of the amino acids in the N-terminal 'DAGX' motif of the coat protein of tobacco vein mottling virus (TVMV) that have a direct effect on aphid transmissibility of the virion were further defined by site-directed mutagenesis. In the first position of the DAGX motif, Asp or Asn are required for aphid transmissibility. In the second position, the nonpolar residue Ala, but not the nonpolar Gly or Val or the polar Thr and Ser, is compatible with transmissibility. In the third position, the small, neutral, nonpolar Gly appears to be critical; even substitution of Ala, with a minimal side-chain, drastically reduces transmissibility. Although the amino acid following the DAG sequence is not highly conserved among potyviruses, the presence of an acidic Glu or Asp residue at this position in the TVMV coat protein drastically reduces or abolishes aphid transmissibility. An attempt was made to test the hypothesis that trypsin cleavage of the N terminus is involved in the aphid inoculation process by destroying a trypsin cleavage site downstream from the DAGX motif. While the predicted decrease in transmission occurred from infected plants, there was no effect on the transmission of purified virus. Of the 23 mutations in the DAGX region of TVMV reported here and previously, only two, substitutions of Lys and Arg for Asp, had a detectable adverse effect other than on aphid transmissibility. These, and perhaps other, residues near the N terminus function in some phase of the TVMV life cycle, in addition to aphid transmission.

Amino Acid Sequence↗
PubMed1995

Discrepancy in T cell clonal expansions in synovial fluid and peripheral blood from rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is an autoimmune disease involving the synovial membrane of peripheral joints. T cells specific for self antigens may play a critical role. Identification of T cell receptors (TCR) of such specific T cell clones is very important for treatment, prevention and identification of relevant autoantigens. To identify specific T cells, TCR V beta family repertoire and the clonal expansion of T cells were analyzed in this study. The percentage of V beta 5+ or V beta 8+ cells in the synovial fluid mononuclear cells (SFMCs) was similar to that in the peripheral blood mononuclear cells (PBMCs). However, the percentage of DR+ T cells in the SFMCs was higher (p < 0.01). Analyzing the clonality of T cells in 8 V beta families (V beta 1, V beta 5, V beta 8, V beta 14, V beta 16, V beta 17, V beta 18, V beta 20), clonal expansions in CD8+ T cells from the SFMCs were found more frequently than in the PBMCs. The patterns of clonal expansions were discrepant between the SFMCs and the PBMCs even in the same patient, which suggests several inflamed tissue specific T cell clonal expansions in the SFMCs. These T cell clones might be activated by autoantigens which are not identified yet and responsible for the RA pathogenesis.

Arthritis, Rheumatoid↗
PubMed1995

Inhibition of c-fos proto-oncogene induction by Sch 52900 and Sch 52901, novel diketopiperazine produced by Gliocladium sp.

Sch 52900 (1) and Sch 52901 (2), two new inhibitors of c-fos proto-oncogene induction, have been isolated from the fermentation of broth of the fungal culture (SCF-1168), Gliocladium sp. Along with compounds 1 and 2, a known compound verticillin A (3) was also obtained from the culture. Structure elucidation of 1 and 2, accomplished by analysis of spectral data in comparison with the data of 3, revealed both 1 and 2 were found to be closely related to the verticillin family of diketopiperazines. All three compounds prevented serum-stimulated transcription of the human c-fos promoter, using a fos/lac Z reporter gene assay, with IC50 values of 1.5, 18 and 0.5 microM of 1, 2 and 3, respectively. Northern analysis revealed the exposure of cells to compound 3 causes inhibition of both phorbol ester-induced c-fos induction of serum-induced JE induction in the absence of inhibiting RNA synthesis, as measured by [3H]uridine incorporation. There results suggest that this class of compounds exerts antitumor activity by blocking a signal transduction pathway that is common to and necessary for the induction of at least a subset of immediate early genes involved in cell proliferation.

3T3 Cells↗
PubMed1995

Antitumor effect of keto-diepoxides isolated from the fungus Nattrassia mangiferae.

A novel keto-diepoxide Sch 49209 and its derivative Sch 50672, produced by the fungus Nattrassia mangiferae, inhibited tumor cell invasion through an artificial basement membrane. These compounds, at nontoxic concentrations, inhibited invasion of HT-1080 cells in a dose-dependent manner. The IC50 values for Sch 49209 and Sch 50672 were 0.75 and 8 microM, respectively, when cells were incubated with drugs for 5 h. Sch 49209 inhibited both tumor cell invasion and cell motility to the same extent under conditions that did not cause any apparent cytotoxicity. Sch 4209 and Sch 50672, however, inhibited the growth of ras-transformed cells in a semisolid medium in a 5-day culture with IC50 values of 0.6 and 2.4 microM, respectively. They also inhibited the anchorage-dependent growth of pT24 cells in vitro with IC50 values of 0.5 and 0.9 microM for Sch 40209 and Sch 50672, respectively. Using the murine lung epidermoid carcinoma M27 cells implanted SC in mice as a model, we found both Sch 49209 and Sch 50672 inhibited the growth of this tumor at doses ranging from 2 to 10 mg/kg. These compounds also decreased the formation of spontaneous lung metastasis in this model. Sch 50672 inhibited the growth of human tumor xenografts, SW620 and A431, in athymic mode mice. Our data suggest that keto-diepoxides inhibit tumor growth and metastasis and that this activity may be due, in part, to anti-invasive activity.

Animals↗
PubMed1995

Transesophageal indirect atrial pacing for open-heart surgery in children.

BACKGROUND: Transesophageal atrial pacing (TAP) has been successfully applied for clinical use for more than 30 years. Not only for cardiac pacing, or diagnosis and treatment of rhythmic disturbance but also for assessing the presence and severity of coronary artery disease and maintaining adequate heart rate can TAP provide satisfactory effect. In this study we applied TAP on children undergoing the cardiac surgery to evaluate its efficacy and side effects during such major surgery. METHODS: Twenty-four children (15 M and 9 F) undergoing open-heart surgery with informed consents were included in this study. After induction of anesthesia the bipolar pacing electrode (Tapcath, Arzco Medical Electronics) was inserted into esophagus through the nose until the ideal site for atrial pacing was found by monitoring the esophageal ECG lead (lead I), and then initiation of atrial pacing was performed by applying the transesophageal cardiac stimulator (Arzco Medical Electronics). Continuous ECG, arterial blood pressure and central venous pressure (CVP) were simultaneously monitored and recorded. Patient's height, inserted length of the pacing electrode, current and pulse duration for effective atrial pacing were also recorded. RESULTS: The effective rate for initiating sinus tachycardia (atrial capture) by applying TAP was 79.2% (19/24) in our study. For effective atrial pacing the average current was 11.6 +/- 2.4 mA, the average stimulus pulse duration was 4.8 +/- 1.0 ms, and the average inserted length of bipolar electrode was 19.1 +/- 2.2 cm. CONCLUSIONS: TAP method can be applied satisfactorily in children undergoing cardiac surgery. If urgent cardiac pacing must be applied in these patients TAP would be a choice.

Arrhythmias, Cardiac↗
PubMed1995

Effects of graded glutamine intake on liver protein metabolism following partial hepatectomy.

OBJECTIVE: To elucidate whether glutamine can influence the rate of regeneration and protein metabolism in regenerating liver. DESIGN: Liver regeneration rate, protein content and synthesis were measured in rats 7 days after a liver resection or sham operation. After the operation, the rats were fed three elementary isonitrogenous diets, one without and two including different levels of glutamine. METHODS: Fifty-six rats were randomly assigned to either sham operation or liver resection. After the operation, they received an isonitrogenous, isocaloric elementary diet with a glutamine content of 0, 2 or 4%. The resected part of the liver was weighed and analysed for DNA and protein content. Seven days later, hepatic protein synthesis was measured by the flooding method using L-[3H]-phenylalanine, and the liver was analysed for DNA, RNA and protein content. RESULTS: The regeneration rate was higher in the group receiving 2% glutamine but not in the group receiving 4% glutamine than in the 0% group. Total protein content was increased in regenerating liver in the 2 and 4% glutamine groups compared with the 0% group. Protein synthesis was higher 7 days after liver resection than in sham-operated rats. In the 2% group there was a tendency towards increased protein synthesis compared with the 0% group. CONCLUSION: A diet with normal glutamine content improved liver regeneration rate, total protein content and protein synthesis in regenerating liver, but an excess of glutamine did not enhance this effect.

Animals↗
PubMed1994

Endogenous hypercholecystokininemia, but not aspirin, reduces the gallstone incidence in the hamster model.

BACKGROUND: Studies in humans and rodents indicate that gallstone development may be prevented by inhibiting gallbladder mucus hypersecretion with non-steroidal anti-inflammatory drugs or by preventing stasis of gallbladder bile with administration of cholecystokinin. METHODS: The effect of oral aspirin and pancreaticobiliary diversion with endogenous hypercholecystokininemia on crystal and gallstone formation was studied in Syrian golden hamsters fed a lithogenic diet for 8 weeks. RESULTS: None of the control animals fed a normal diet developed gallstones or crystals in gallbladder bile. Gallstones developed in 67% of the animals fed a lithogenic diet only. The gallstone prevalence did not differ significantly in animals on a lithogenic diet and a daily aspirin dose of 6 mg/kg (gallstone prevalence, 60%) or 100 mg/kg (gallstone prevalence, 70%), whereas it was significantly lower in animals with endogenous hypercholecystokininemia on a lithogenic diet (gallstone prevalence, 29%). The prevalence of crystals in gallbladder bile did not differ significantly between any of the experimental groups. CONCLUSIONS: It is concluded that in hamsters on a lithogenic diet, aspirin does not prevent gallstone formation, whereas endogenous hypercholecystokininemia reduces the prevalence of stones without affecting the occurrence of crystals in gallbladder bile.

Animals↗
PubMed1994

Novel ketoepoxides block phospholipase D activation and tumor cell invasion.

The functional significance of phospholipase D (PLD) could most easily be investigated using selective inhibitors. We have isolated a family of fungal metabolites, ketoepoxides, that inhibit chemotactic peptide (formyl-Met-Leu-Phe)-stimulated PLD activation and superoxide generation in granulocytes in the low micromolar range (SCH 49210 having an IC50 of 1.6 microM). Unlike receptor-mediated PLD activation, ketoepoxides were poor inhibitors of phorbol ester-induced PLD activity in granulocytes (IC50 = 43 microM for SCH 49210). Ketoepoxides did not inhibit platelet-derived growth factor-stimulated PLD activity in fibroblasts at up to 50 microM. We also tested the effect of ketoepoxides on in vitro epidermal growth factor receptor and neu tyrosine kinase activities. SCH 49210 (and 49209) did not inhibit the tyrosine kinases at up to 100 microM. These results suggest that ketoepoxides do not inhibit PLD activation due to effects on tyrosine kinase activity. fMLP-induced phospholipase A2 (PLA2) activation is also inhibited by ketoepoxides in the low micromolar range (SCH 49210 having an IC50 of 3.2 microM), but the ketoepoxides were poorer inhibitors of Ca2+ ionophore A23187-induced PLA2 (SCH 49210 having an IC50 of 83 microM). As a measure of phospholipase C (PLC) activity, the generation of inositol-1,4,5 triphosphate in thrombin-stimulated platelets was measured. The ketoepoxides did not inhibit PLC activation indicating that, unlike the aminosteroid U73122, ketoepoxides exhibit some selectivity among receptor-linked phospholipases. The ketoepoxides were also effective inhibitors of tumor cell invasion, as measured by penetration of HT1080 human fibrosarcoma cells into a reconstituted basement membrane matrix. Interestingly, both PLD inhibition and anti-tumor invasion activity correlate closely. These ketoepoxides are, therefore, potential anti-metastatic compounds and may be useful probes to study the role of PLD in cell function.

Enzyme Activation↗
PubMed1994

Effects of gastric fundusectomy and antrectomy on gallbladder epithelial proliferation in the hamster.

BACKGROUND: Exogenous administration of cholecystokinin or its analog cerulein induces epithelial hyperplasia in the mouse gallbladder. The effects on the gallbladder of resectional surgery of the stomach with hormonal consequences are not known. METHODS: The effects of gastric fundusectomy and antrectomy on proliferation and growth of the gallbladder epithelium were studied in male Syrian golden hamsters during periods of 5 and 25 days. Sham-operated animals served as controls. RESULTS: Basal plasma gastrin concentrations were significantly increased after fundusectomy and significantly decreased after antrectomy, whereas basal plasma cholecystokinin concentrations were not significantly affected. Five days after fundusectomy, there was a significant increase in the tritiated thymidine DNA labeling index of gallbladder epithelial cells. On day 25, the gallbladder weight and total number of epithelial cells were significantly increased after fundusectomy. Antrectomy significantly decreased the gallbladder weight on day 25, whereas the labeling index and total number of epithelial cells were not significantly affected on days 5 and 25. CONCLUSIONS: These results suggest that gastric fundusectomy at least transiently induces gallbladder epithelial hyperplasia and hypertrophy in the hamster. Although achlorhydria and hypergastrinemia are prominent features, the actual mechanism behind this effect of fundusectomy on the gallbladder needs further clarification.

Animals↗