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Biomedical subjects

B Wu

Publications and source records attributed to B Wu.

At least 199 records · Page 11Linked to original sources

[Growth regulatory mechanisms of recombinant human interleukin-6 on human lung carcinoma cell lines].

OBJECTIVES: To detect the activity of interleukin-6 (rhIL-6) on human lung cancer and the influences of recombinant human IL-6 (rhIL-6) on the in vitro growth of high-metastatic human lung giant cell carcinoma cell line PG and low-metastatic human lung adenocarcinoma cell line PAa. METHODS: The effects of rhIL-6 on the expressions of IL-6, IL-6R, c-myc, c-fos and c-jun mRNAs were analyzed by Northern blotting hybridization. RESULTS: rhIL-6 could stimulate the in vitro growth of both PG and PAa cells, in a dose-and-time-dependent manner. Both PG and PAa cells were shown to express IL-6 and IL-6R identified by reverse transcription PCR analysis. Northern blotting hybridization revealed that rhIL-6 up-regulated mRNA levels of IL-6, IL-6R and c-myc rather than those of c-fos and c-jun. CONCLUSION: These data suggest that rhIL-6 may promote the proliferation of human lung cancer cell lines PG and PAa, which might, at least partly, be related to the up-regulation of expressions of IL-6, IL-6R, c-myc gene transcript.

Adenocarcinoma↗

[The development of a fluid percussion device for brain injury of animals].

This paper discusses a fluid percussion device for brain injury. The injury is produced by striking the cork with a pendulum dropped from a known fall height to produce transient high pressure through a fluid transfer system. Experimental results show the device has the advantages of making a controllable, repeatable, and precise injury, and it can produce different levels of injury on different animals.

Animals↗

IFN-alpha therapy is effective in suppressing the clinical experimental myasthenia gravis.

To study the therapeutic efficacy of IFN-alpha after the onset of clinical signs of experimental autoimmune myasthenia gravis (EAMG), we treated mice with clinical EAMG with recombinant human IFN-alpha or mouse IFN-alpha. In the first experiment, 7 of 16 (44%) mice had a complete clinical remission in the recombinant human IFN-alpha-treated group, in contrast to none in the placebo group (0/14) (p = 0.006). There was a higher incidence of death and severe disease in the placebo group (7/14) relative to the IFN-alpha group (4/16). In the second experiment, 6 of 18 (33%) mice in the mouse IFN-alpha-treated group had a complete clinical remission, while none of 17 (0%) mice in the placebo-treated group had remission (p = 0.011). Again, more mice died or worsened in the placebo group (11/17) compared with the IFN-alpha group (7/18). IFN-alpha treatment significantly reduced the anti-acetylcholine receptor (AChR) Ab levels, especially the IgG1 and IgG2b isotypes, and the amount of anti-AChR Abs bound to muscle AChR. IFN-alpha treatment also lowered CD4 cells in the lymph nodes and spleen, and suppressed the in vitro lymphocyte proliferative response to AChR and its dominant peptide in a dose-dependent manner.

Animals↗

Structure-function analysis of the Escherichia coli GrpE heat shock protein.

We have isolated various missense mutations in the essential grpE gene of Escherichia coli based on the inability to propagate bacteriophage lambda. To better understand the biochemical mechanisms of GrpE action in various biological processes, six mutant proteins were overexpressed and purified. All of them, GrpE103, GrpE66, GrpE2/280, GrpE17, GrpE13a and GrpE25, have single amino acid substitutions located in highly conserved regions throughout the GrpE sequence. The biochemical defects of each mutant GrpE protein were identified by examining their abilities to: (i) support in vitro lambda DNA replication; (ii) stimulate the weak ATPase activity of DnaK; (iii) dimerize and oligomerize, as judged by glutaraldehyde crosslinking and HPLC size chromatography; (iv) interact with wild-type DnaK protein using either an ELISA assay, glutaraldehyde crosslinking or HPLC size chromatography. Our results suggest that GrpE can exist in a dimeric or oligomeric form, depending on its relative concentration, and that it dimerizes/oligomerizes through its N-terminal region, most likely through a computer predicted coiled-coil region. Analysis of several mutant GrpE proteins indicates that an oligomer of GrpE is the most active form that interacts stably with DnaK and that the interaction is vital for GrpE biological function. Our results also demonstrate that both the N-terminal and C-terminal regions are important for GrpE function in lambda DNA replication and its co-chaperone activity with DnaK.

Adenosine Triphosphatases↗

Cloning and characterization of mouse CCAAT binding factor.

Isolation of cDNA clones for the mouse CCAAT binding factor (mCBF) has revealed the expression of two distinct forms of mCBF that are generated by alternative splicing of a single primary transcript from a gene that maps to chromosome 17. The mCBF1 mRNA encodes a protein of 997 amino acids, whereas the mCBF2 protein is predicted to be only 461 amino acids in length; mCBF1 and human CBF (hCBF) share>80% amino acid sequence identity. Analysis of adult mouse tissue RNAs has revealed that the mCBF1 and mCBF2 mRNAs are ubiquitously expressed, but that mCBF1 mRNA is 5- to 10-fold more abundant than mCBF2 mRNA. Similarly, mCBF mRNA was detected through-out the placenta and in all tissues of the developing embryo from day 8 to day 18 of gestation. Overexpression of the two forms of mCBF in mammalian cells has demonstrated that the mCBF1 and mCBF2 proteins localize to different cellular compartments, with mCBF1 found predominantly in the nucleus and mCBF2 restricted to the cytoplasm. Co-expression of these two forms influences their localization, however, indicating that CBF activity can be regulated by the relative amounts of the two forms expressed in a cell.

3T3 Cells↗

Quantitative comparisons of continuous and pulsed low dose rate regimens in a model late-effect system.

PURPOSE: There is increasing interest and usage of pulsed low dose rate (PDR) brachytherapy, in which a single source is shuttled through the catheters of an implant, typically for about 10 min each hour. This study was designed to compare the late effects produced in various PDR regimens with those from the corresponding continuous low dose rate (CLDR) regimens. METHODS AND MATERIALS: A model late-responding system was used, namely, cataract induction in the rat lens. This system has the advantage of being highly quantifiable. The rats eyes were exposed to a total dose of 15 Gy either continuously over 24 h, or with three different PDR regimens, all with the same total dose and overall time. We addressed three questions: (a) are late effects increased when a CLDR regimen is replaced with 10-min pulses repeated every hour? (b) Are late effects increased if hourly 10-min pulses are replaced with 10-min pulses repeated every 4 h? (c) Are late effects increased if 10-min pulses are replaced with 100-s pulses? RESULTS: We found that the four regimens under test, continuous, 10-min pulses each hour, 10-min pulses every 4 h, and 100-s pulses every hour, showed no significant differences in cataractogenic potential, as estimated with the Wilcoxon-Gehan test. Power tests indicated that the experimental design was adequate to detect relatively small differences in cataractogenicity between regimens. CONCLUSIONS: The equality of late effects from CLDR and PDR in these experiments must imply that sublethal damage repair is quite slow in this model late-responding system, in agreement with trends observed in the clinic for sublethal damage repair of late sequelae. Such trends would suggest that PDR is unlikely to produce significantly worse late effects than the corresponding CLDR regimen, which is in agreement with early clinical data using PDR. Caution, however, is strongly recommended.

Animals↗

Temporal distinctions in the synthesis and accumulation of proteins by oocytes and cumulus cells during maturation in vitro of bovine oocytes.

Successful in vitro maturation (IVM) of bovine oocytes requires continual and/or episodic protein synthesis by cumulus-oocyte complexes. This study was designed to expose time-dependent changes in protein synthesis and accumulation by bovine oocytes and cumulus cells during routine IVM. Silver staining after sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated little if any change in protein species present or their relative contents in oocytes during IVM; one notable exception, however, was the gradual accumulation of a 39-kDa polypeptide between 4-24 hr of maturation culture. Cumulus cells, on the other hand, exhibited no qualitative differences during the period examined, but total protein content did increase during IVM. Metabolic labeling with [35S]-methionine, however, demonstrated changes in protein synthesis, both quantitative and qualitative, by both cell types. Oocytes exhibited a steady or slightly increasing rate of synthesis during the first 12 hr of IVM; thereafter, protein synthesis declined to about 10% of the initial rate by 40 hr in culture. In contrast, protein synthesis in cumulus cells was relatively constant during the first 24 hr. Of greater interest is the demonstration that the synthesis of at least seven oocyte-specific and five cumulus-specific proteins was stage-dependent during maturation. These results indicate that maturation of bovine oocytes is associated with the synthesis of several distinct and temporally expressed proteins which may play roles in the highly ordered sequence of events that culminates in oocyte maturation.

Animals↗

Indoor burning coal air pollution and lung cancer--a case-control study in Fuzhou, China.

A case-control study on risk factors for lung cancer was carried out in Fuzhou, China. One-hundred and two newly-diagnosed primary lung cancer cases in urban Fuzhou (78 male and 24 female cases) were matched with 306 population-based controls. The primary histological types were adenocarcinomas (57 cases, 55.9%) and squamous cell carcinomas (39 cases, 38.2%). Controls were obtained from the general population by random, stratified sampling and consisted of noncancer cases matched for sex, ethnicity and age. Cases and controls were interviewed by trained professionals using a standardized questionnaire. Information was obtained on: smoking habits, living conditions, history of respiratory diseases, air pollution, and 40 other variables. The data were evaluated by conditional logistic regression analysis. The major risk factors for lung adenocarcinoma were: indoor air pollution from burning coal, chronic bronchitis, and high economic income. The risk factors for lung squamous cell carcinoma were: amount of cigarettes smoked per day, "deep inhalation", a history of exposure to environmental tobacco smoke (ETS) before 20 years of age, burning coal indoors, and high economic income. The results showed that the major risk factors for lung cancer in Fuzhou were: burning coal indoors, smoking, exposure to ETS before 20 years of age, chronic bronchitis, and high economic income. Cigarette smoking significantly increased the risk of lung squamous cell carcinoma, but had no significant association with the risk of lung adenocarcinoma. In summary, our research supports the hypothesis that smoking and indoor air pollution are the major risk factors for lung cancer in Fuzhou. Burning coal indoors and smoking were associated with lung cancer mortality in a major city in southern China.

Adult↗

Expression of c-fos and c-jun proto-oncogenes by ovine preimplantation embryos.

The c-fos and c-jun proto-oncogenes are involved in the regulation of gene expression, cell proliferation, differentiation and tumorigenesis. Embryogenesis, like tumorigenesis, involves dramatic cell growth, cleavage and differentiation processes. Activation of the c-fos and c-jun proto-oncogenes in sheep conceptuses during the period of rapid growth and elongation was examined using reverse transcription and polymerase chain reaction (RT-PCR). The specificity of PCR products was determined by Southern blot hybridisation analysis with a non-radioactive DNA probe. A band corresponding to a 507 bp fragment (predicted amplified c-fos gene cDNA product) was observed in 3 of 9 day-13, 1 of 4 day-14 and 1 of 2 day-16 embryos. Meanwhile, a 400 bp c-jun transcript was also detected in 1 of 2 day-12, 3 of 9 day-13 and 2 of 2 day-16 embryos. These results suggest that mRNA transcripts of c-fos and c-jun proto-oncogenes were specifically expressed during the period of ovine embryonic elongation and may have a possible role in preimplantation embryonic development of sheep.

Animals↗

Adhesion molecule interactions in human glomerulonephritis: importance of the tubulointerstitium.

Infiltration of leukocytes into glomerular and interstitial regions of the kidney is a key event in the pathogenesis of human glomerulonephritis. This process is mediated by specific adhesion molecules, some of which are expressed in a coordinated fashion following endothelial cell activation. We have assessed the pattern of expression of the selectins (E, P and L), and the counter-receptors (LFA-1 and ICAM-1, and VLA-4 and VCAM-1 in 119 renal biopsies using sequential sections, and have correlated this with the degree of histological damage (tubular atrophy and interstitial fibrosis) and the intensity of the macrophage infiltrate. Sections were stained with the monoclonal antibodies using a standard alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. There were strong correlations between the following: (1) expression of LFA-1, VLA-4, and L-selectin in the periglomerular region, interstitium and in focal interstitial infiltrates and the presence of macrophages in these regions; (2) de novo tubular expression of ICAM-1 and VCAM-1; (3) staining for ICAM-1 and VCAM-1 on focal cellular infiltrates within the interstitium; and (4) staining for E- and P-selectin on extraglomerular endothelium. These are also strongly correlated with the degree of chronic histological damage. There was, however, no correlation between glomerular expression of adhesion molecules or glomerular macrophage infiltration and chronic histological damage. Although expression of VCAM-1 by the glomerular mesangium was strongly correlated with the presence of cells staining for VLA-4 within the glomerulus, glomerular expression of adhesion molecules correlated poorly with their expression in other sites. These results show that coordinated up-regulation of adhesion molecule expression in the tubulointerstitium is associated with interstitial fibrosis and tubular atrophy and may contribute, therefore, to the progression of renal disease.

Biopsy↗

CD44 in glomerulonephritis: expression in human renal biopsies, the Thy 1.1 model, and by cultured mesangial cells.

CD44 is a transmembrane proteoglycan that serves as a cell adhesion receptor and is involved in cell-cell and cell-matrix interactions, both key events in the pathogenesis of clinical and experimental glomerulonephritis. In addition, recent evidence suggests that the binding of cytokines to proteoglycans could regulate cytokine function. We have, therefore, studied the expression of CD44 by mesangial cells in culture and in experimental (Thy 1.1 model) and human glomerulonephritis. Mesangial expression of CD44 detected by immunohistochemistry was markedly increased four days after induction of the Thy 1.1 model, coinciding with the peak of mesangial cell proliferation and macrophage infiltration. Analysis of 92 human renal biopsies by immunohistochemistry showed that CD44 expression by infiltrating cells within the glomerulus, in focal interstitial infiltrates and within the interstitium (interstitial fibroblasts, and extracellular matrix), was significantly increased in biopsies with a greater degree of histological damage. There was, however, no increase in mesangial staining in diseased kidneys as compared with control sections. In contrast, cultured human mesangial cells expressed CD44 strongly when assayed by immunohistochemistry, immunoprecipitation and Northern blotting. CD44, therefore, is an example of a protein strongly expressed by mesangial cells in vitro and weakly or not at all in vivo, but which is up-regulated in a disease model. In human disease, however, little expression was detected within the glomerular mesangium, which may be related to the greater proliferation and more profound disruption of mesangial architecture seen in the Thy 1.1 model. CD44 expression by infiltrating cells and by components of the interstitium could, however, play an important role in the pathogenesis of chronic progressive renal disease in humans.

Animals↗

Electroencephalographic burst suppression is not required to elicit maximal neuroprotection from pentobarbital in a rat model of focal cerebral ischemia.

BACKGROUND: Barbiturates have previously been demonstrated to reduce focal cerebral ischemic brain damage. However, the dose of drug required to elicit maximal neuroprotection has not been defined. The authors' hypothesized that doses of pentobarbital substantially lower than those required to cause electroencephalographic burst suppression would result in maximal magnitudes of reduction of cerebral infarct volume. METHODS: Wistar rats underwent 90 min of filament occlusion of the middle cerebral artery while either awake (control), or anesthetized with intravenous sodium pentobarbital administered to preserve an active electroencephalogram (15-23 mg.kg-1.h-1) or a pattern of burst suppression (45-60 mg.kg-1.h-1; n = 17). During ischemia and for the first 6 h of recirculation, brain temperature was rigorously controlled at 38.0 +/- 0.2 degrees C. Rats were allowed a recovery interval of 7 days after which neurologic function and cerebral infarct volume were assessed. In nonischemic rats undergoing a similar anesthetic protocol, the cerebral metabolic rate of glucose utilization was measured at each anesthetic depth. RESULTS: Relevant physiologic values were similar between groups. Total infarct volume (mean +/- SD) was smaller in the active electroencephalogram group than in the control group (124 +/- 68 mm3 versus 163 +/- 66 mm3; P < 0.05). Increasing the dose of pentobarbital (burst suppression) did not further decrease infarct volume (128 +/- 54 mm3). Neurologic score and infarct volume were positively correlated (P < 0.001). Cerebral metabolic rate of glucose utilization was reduced by 56% in the burst suppression group versus 43% in the active electroencephalogram pentobarbital group (P < 0.001). CONCLUSIONS: Sodium pentobarbital administered at either dose (active electroencephalogram or burst suppression) resulted in an approximately equal to 25% reduction of cerebral infarct size, indicating that burst suppression is not required to elicit maximal neuroprotective efficacy.

Animals↗

Hypermagnesiuria and hypercalciuria in childhood leukemia: an effect of amikacin therapy.

PURPOSE: The purpose of this study is to assess the effects of amikacin on renal proximal tubular function, and on magnesium (Mg) and calcium (Ca) status in children treated for acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Eighteen children (11 male/7 female, ages 2-18 years) receiving antileukemic therapy (Dana Farber Cancer Institute protocols 87-001 or 91-001) and admitted for febrile neutropenia to The Children's Hospital at Chedoke-McMaster, Hamilton, Ontario were recruited into this descriptive prospective study. Each child was treated with amikacin (7.5 mg/kg/12 h x 10-14 days) for one or more courses. RESULTS: No patient demonstrated elevations in amikacin trough levels. beta 2-Microglobulinuria, glucosuria, proteinuria, and hyperphosphaturia were absent. Children (50% presenting with hypomagnesemia (< 0.77 mmol/L) had a significant rise in mean urinary Mg:creatinine (0.46 +/- 0.27 versus 0.82 +/- 0.38 mmol, mean +/- SD, p < 0.05) in response to amikacin therapy and the mean Ca:creatinine ratio increased by 95% after 10-14 days of amikacin treatment. Serum Mg and Ca did not change notably after treatment, irrespective of initial Mg status. CONCLUSIONS: Aminoglycoside therapy in children with ALL is not associated with overt nephrotoxicity. A transient renal leak of Mg and Ca does occur. Screening of ALL children for mild hypomagnesemia may help to identify those most at risk of disruption of renal conservation of Mg and possibly Ca.

Adolescent↗

Antiviral and resistance studies of AG1343, an orally bioavailable inhibitor of human immunodeficiency virus protease.

AG1343 ([3S-(3R*,4aR*,8aR*,2'S*,3'S*)]-2-[2' hydroxy-3'-phenylthiomethyl-4'-aza-5'-oxo-5'-(2''-methyl-3''-hydro xy-phenyl) pentyl]-decahydroiso-quinoline-3-N-t-butylcarboxamide methanesulfonic acid) is a selective, nonpeptidic inhibitor of human immunodeficiency virus (HIV) protease (Ki = 2 nM) that was discovered by protein structure-based drug design methodologies. AG1343 was effective against the replication of several laboratory and clinical HIV type 1 (HIV-1) or HIV-2 isolates including pyridinone- and zidovudine-resistant strains, with 50% effective concentrations ranging from 9 to 60 nM. In reversibility studies, inhibition of gag (p55) proteolytic processing in HIV-1 particles from cells treated with AG1343 was maintained for up to 36 h after drug removal. The ability of virus to develop resistance to AG1343 was studied by serial passage of HIV-1 NL4.3 in the presence of increasing concentrations of drug. After 28 passages, a variant with a 30-fold reduction in susceptibility to AG1343 was isolated. Molecular analysis of the protease from this variant indicated a double change from a Met to Ile at residue 46 and an Ile to Val or Ala at residue 84 (M46I+I84V, A). Consistent with these findings, reductions in susceptibility were observed for recombinant viruses constructed to contain the single I84V change or the double M46I+I84V substitutions. Resistance, however, was not detected for recombinant viruses containing other key mutations in HIV-1 protease, including a Val to Ile change at residue 32 or a Val to Ala or Phe at residue 82. The potent anti-HIV activity of AG1343 against several isolates suggests that AG1343 should perform well during ongoing human phase II clinical trials.

Amino Acid Sequence↗

Infection of primary CD4+ and CD8+ T lymphocytes by Epstein-Barr virus enhances human immunodeficiency virus expression.

CD4+ and CD8+ T lymphocytes purified from normal adult donors by flow cytometry could be infected with Epstein-Barr virus (EBV) as measured by the accumulation of components of the EBV replicative cycle, viral DNA and viral transcripts encoding EBER1 and BRLF1. EBV infection resulted in enhanced replication of human immunodeficiency virus type 1 (HIV-1) IIIB in CD4+ lymphocytes as measured by accumulation of reverse transcriptase and formation of syncytia. Furthermore, a small percentage of CD8+ T cells became permissive after infection with EBV. Inactivation of transforming functions by irradiation with UV light greatly reduced the ability of EBV to enhance HIV-1 replication in T4+ T cell, suggesting that live virus is needed for enhancement. These results demonstrate a direct synergy between EBV and HIV-1 during coinfection of T cells in vitro and may explain the beneficial effect of acyclovir in combination with antiretroviral chemotherapy as well as the increased incidence of T-cell lymphomas associated with EBV in patients with AIDS.

Adult↗

A study of the demographic characteristics of domestic tourists.

"A sample survey was conducted [in China]: more than 6,000 questionnaires were submitted and retrieved from domestic tourists in Shanghai, Xi'ian, Huangshan, and Huashan in order to provide data for demographic analysis of the special fluid population of tourists. The paper looks at the relationship between tourists' gender, age, income, occupation, education, and family structure, as well as their tourist activity, selection of destinations, shopping, and other tourist behaviors."

Asia↗

[Effect of kanggusong in prevention and treatment of retinoic acid induced osteoporosis in rats].

Retinoic acid 70 mg/kg.d was given by gastrogavage to Wistar rat for 14 days to induce osteoporosis. Kanggusong (KGS), a mixture of extracts from 8 traditional Chinese drugs, was given to 3 test groups of rats simultaneously in various dosage. Results showed that the KGS displayed obvious action in preventing osteoporosis, the trabecular loss of tibiae and bone loss of compact bone were lowered markedly in KGS groups with high (3.0 g/kg.d) or middle (1.0 g/kg.d) dosage in comparing with control model group, the trabecular area percentage and compact bone area percentage were increased significantly (P < 0.05) which approached to the level of normal control group. KGS could also improve the pathological changes in microstructure of bone, increase the thickness of trabecula and cortex (P < 0.05), reduce the trabecular gap and bone marrow cavity (P < 0.05). The mechanism of KGS might be relevant with its action of suppressing the osteoclast activity and activating osteoblast, resulting a positive balance of bone metabolism, increasing the blood concentration of calcium and estrogen as well as its antagonistic action against the injury of sex glands by retinoic acid.

Animals↗