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Biomedical subjects

F Wang

Publications and source records attributed to F Wang.

At least 667 records · Page 37Linked to original sources

Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration.

Systemic infusion of low concentrations of tumor necrosis factor/cachectin (TNF) into mice that bear TNF-sensitive tumors leads to activation of coagulation, fibrin formation, and occlusive thrombosis exclusively within the tumor vascular bed. To identify mechanisms underlying the localization of this vascular procoagulant response, a tumor-derived polypeptide has been purified to homogeneity from supernatants of murine methylcholanthrene A-induced fibrosarcomas that induces endothelial tissue factor synthesis and expression (half-maximal response at approximately 300 pM), and augments the procoagulant response to TNF in a synergistic fashion. This tumor-derived polypeptide was identified as the murine homologue of vascular permeability factor (VPF) based on similar mobility on SDS-PAGE, an homologous NH2-terminal amino acid sequence, and recognition by a monospecific antibody to guinea pig VPF. In addition, VPF was shown to induce monocyte activation, as evidenced by expression of tissue factor. Finally, VPF was shown to induce monocyte chemotaxis across collagen membranes and endothelial cell monolayers. Taken together, these results indicate that VPF can modulate the coagulant properties of endothelium and monocytes, and can promote monocyte migration into the tumor bed. This suggests one mechanism through which tumor-derived mediators can alter properties of the vessel wall.

Amino Acid Sequence↗

Actin critical concentration optimizes at intermediate [cytochalasin B]/[actin] ratios.

Effect of cytochalasin B on actin critical concentration has been assayed using the fluorescence enhancement of pyrene-labeled actin. A peak effect of cytochalasin B on the critical concentration is observed in the presence of either 100 mM K+, or 100 mM K+ plus 2 mM Mg2+. This may result from two competing activities of cytochalasin B, one associated with its capping activity to the barbed end of actin filaments, and the other associated with its lateral binding site(s) along the filaments resulting in a severing activity of cytochalasin B.

Actins↗

The carriage of Escherichia coli resistant to antimicrobial agents by healthy children in Boston, in Caracas, Venezuela, and in Qin Pu, China.

BACKGROUND AND METHODS: The healthy members of a community represent its largest reservoir of bacteria resistant to antimicrobial agents. We compared the resistance to eight agents of Escherichia coli in stool samples from untreated, healthy children in cities on three continents. RESULTS: When screened by a selective method that detected 1 resistant colony in 10,000 colonies, nearly half the children in Boston (18 of 39) had no resistant colonies--a finding consistent with the findings of other surveys performed in developed countries. However, all but 1 of 41 children screened in Caracas, Venezuela, and all but 2 of 53 in Qin Pu, China, carried resistant strains. Only 1 child in Boston but 25 in Caracas and 34 in Qin Pu carried strains resistant to trimethoprim. None of the children in Boston or Caracas but 17 in Qin Pu carried strains resistant to gentamicin. Among 10 colonies selected randomly from each stool sample, the average frequency of resistance in Caracas was 3.6 times greater than in Boston, and that in Qin Pu was 5.3 times greater. There was resistance to five or more antimicrobial agents in 20 percent of the Qin Pu strains and in 6 percent of the Caracas strains but in none of the Boston strains. CONCLUSIONS: In addition to clinical isolates, as reported previously, the bacteria that colonize health children in the community may be resistant far more often in some regions than in others. A low rate of carriage of antimicrobial resistance in the community should become a public health goal.

Anti-Bacterial Agents↗

Inhibition of mitochondrial respiration by analogues of the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium: structural requirements for accumulation-dependent enhanced inhibitory potency on intact mitochondria.

Analogues of 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, were evaluated for inhibition of respiration in intact mitochondria (Mw) and in electron transport particles (ETP). MPP+ exhibits relatively weak inhibitory activity in ETP, but potent inhibition in Mw occurs on account of its energy-dependent accumulation inside mitochondria. The permeant anion tetraphenylborate potentiates the inhibition in both Mw and ETP. Replacement of the 4-phenyl ring of MPP+ by a variety of aromatic and nonaromatic rings, and of the N-methylpyridinium group by other cationic aromatic heterocycles, preserves the inhibitory patterns seen for MPP+. The general observation of enhanced inhibitory potency in Mw for all these permanently charged cations is consistent with our contention that energy-dependent accumulation inside mitochondria represents a passive Nernstian concentration in response to the transmembrane electrochemical gradient. Nonetheless, the magnitude of the inhibitory potentiation seen in Mw relative to ETP varies widely with structure. In particular, less lipophilic analogues, especially those bearing a localized, rather than resonance-stabilized, permanent positive charge, exhibit similar inhibitory activity to MPP+ in ETP, but the inhibition in Mw is not comparably enhanced. For these same analogues, the inhibitory activity in ETP is only weakly potentiated by tetraphenylborate. Since succinate was found to completely reverse the respiratory inhibition in Mw induced by all types of MPP+ analogues investigated, a common site 1 inhibition appears to be involved; thus the different inhibitory patterns observed must be due to structural factors governing membrane transport and distribution properties.

1-Methyl-4-phenylpyridinium↗

The use of proteolysis and direct N-terminal sequence analysis to study human interleukin-2/receptor interaction on solid support.

An immobilized interleukin-2 receptor which is capable of binding interleukin-2 and suitable for direct N-terminal sequence analysis was employed to study interleukin-2/receptor interactions. Sensitive tryptic sites on the immobilized receptor and its interleukin-2 complex were identified by sequence analyses and compared. The results have revealed that the N-terminal region of interleukin-2 is not involved in receptor binding and the peptide segment covering residues 36-39 in the receptor is probably near or involved in the interleukin-2 binding site. The rapidity and simplicity make this solid phase sequence approach a good method for analyzing interleukin-2/receptor interaction and may be suitable for studying other protein-ligand interactions.

Amino Acid Sequence↗

Expression of the Epstein-Barr virus (EBV)-encoded membrane antigen (LMP) increases the stimulatory capacity of EBV-negative B lymphoma lines in allogeneic mixed lymphocyte cultures.

Epstein-Barr virus (EBV)-negative Burkitt lymphoma (BL) lines are poor stimulators in allogeneic mixed lymphocyte cultures compared to EBV-transformed lymphoblastoid cell lines derived from the same individuals. We have previously shown that the stimulatory capacity of the tumor cells is increased after EBV conversion (Avila-Carino et al., Int. J. Cancer 1987. 40: 691). As a first step towards the identification of the viral gene product responsible for this change we have studied the influence of the EBV latent membrane protein (LMP) on the stimulatory capacity of the EBV-negative BL lines BL41 and DG75 and the B lymphoma line BJAB. Four LMP-transfected sublines of BL41, four DG75 LMP transfectants and one LMP-transfected subline of BJAB showed a significantly stronger stimulatory capacity than the original line. The effect was directly proportional to the amount of LMP detected in each transfectant but was not due to reactivation of LMP-specific memory cells since lymphocytes from EBV-seropositive and -seronegative individuals responded equally. In order to define the relation between LMP expression and induction of stimulatory capacity, DG75 was transfected with constructs containing the LMP gene under the control of an heat-shock promoter. The peak of LMP expression in heat shock-treated cells preceded the appearance of stimulatory capacity by 6-12 h suggesting that critical amounts of the protein may be required to induce the phenotypic change recognized by the T cells. LMP influenced in a dose-dependent manner the expression of the adhesion molecules LFA-1, LFA-3 and ICAM-1 and B cell activation markers CD23 and CD39 in transfected sublines of BL41, but did not affect the expression of these markers in the DG75 and BJAB cell line. All LMP-expressing transfectants showed an increased capacity to form conjugates with unprimed allogeneic lymphocytes.

Antibodies, Monoclonal↗

Estimating rates of change in randomized clinical trials.

This article deals with the extension of the pretest-posttest clinical trial to the longitudinal data setting. We assume that a baseline (or pretest) measurement is taken on all individuals, who are then randomized, without regard to baseline values, to a treatment group. Repeated measurements are taken postrandomization at specified times. Our objective is to estimate the average rate of change (or slope) in the experimental groups and the differences in the slopes. Our focus is on the optimal use of the baseline measurements in the analysis. We contrast two different approaches:--a multivariate one that regards the entire vector of responses (including the baseline) as random outcomes and a univariate one that uses each individual's least squares slope as an outcome. Our multivariate approach is essentially a generalization of Stanek's Seemingly Unrelated Regression (SUR) estimator for the pretest-posttest design. The multivariate approach is natural to apply in this setting, and optimal if the assumed model is correct. However, the most efficient estimator requires assuming that the baseline mean parameters are the same for all experimental groups. Although this assumption is reasonable in the randomized setting, the resulting multivariate estimator uses postrandomization data as a covariate; if the assumed linear model is not correct, this can lead to distortions in the estimated treatment effect. We propose instead a reduced form multivariate estimator that may be somewhat less efficient, but protects against model misspecification.

Analysis of Variance↗

The lack of relationship between acetylator phenotype and idiopathic systemic lupus erythematosus in a South-east Asian population: a study of Indians, Malays and Malaysian Chinese.

An association of idiopathic systemic lupus erythematosus (ISLE) with genetically determined N-acetylation polymorphism has been suspected from previous studies, mainly on Caucasian populations in which there is an approximate incidence of 50% of slow and rapid acetylators. The present study is of the incidence of ISLE and acetylator status in a mixed population of Malaysia. The results did not support an association between ISLE and acetylator status: the frequencies of slow acetylators in the ISLE patients who were Malaysian Chinese and Malay were 13 and 38% respectively. This did not differ significantly from the respective healthy groups (20 and 29%). The small number of Indians in the survey did not allow a valid comparison, but the figures did suggest a lack of association between ISLE and acetylator status.

Acetylation↗

Epstein-Barr virus nuclear antigen 2 induces expression of the virus-encoded latent membrane protein.

Infection of Epstein-Barr virus-negative human B-lymphoma cell lines with the fully transforming B95.8 Epstein-Barr virus strain was associated with complete virus latent gene expression and a change in the cell surface and growth phenotype toward that of in vitro-transformed lymphoblastoid cell lines. In contrast, the cells infected with the P3HR1 Epstein-Barr virus strain, a deletion mutant that cannot encode Epstein-Barr nuclear antigen 2 (EBNA2) or a full-length EBNA-LP, expressed EBNAs1, 3a, 3b, and 3c but were negative for the latent membrane protein (LMP) and showed no change in cellular phenotype. This suggests that EBNA2 and/or EBNA-LP may be required for subsequent expression of LMP in Epstein-Barr virus-infected B cells. Recombinant vectors capable of expressing the B95.8 EBNA2A protein were introduced by electroporation into two P3HR1-converted B-lymphoma cell lines, BL30/P3 and BL41/P3. In both cases, stable expression of EBNA2A was accompanied by activation of LMP expression from the resident P3HR1 genome; control transfectants that did not express the EBNA2A protein never showed induction of LMP. In further experiments, a recombinant vector capable of expressing the full-length B95.8 EBNA-LP was introduced into the same target lines. Strong EBNA-LP expression was consistently observed in the transfected clones but was never accompanied by induction of LMP. The EBNA2A gene transfectants expressing EBNA2A and LMP showed a dramatic change in cell surface and growth phenotype toward a pattern like that of lymphoblastoid cell lines; some but not all of these changes could be reproduced in the absence of EBNA2A by transfection of P3HR1-converted cell lines with a recombinant vector expressing LMP. These studies suggest that EBNA2 plays an important dual role in the process of B-cell activation to the lymphoblastoid phenotype; the protein can have a direct effect upon cellular gene expression and is also involved in activating the expression of a second virus-encoded effector protein, LMP.

Antigens, Viral↗

Epstein-Barr virus latent membrane protein (LMP1) and nuclear proteins 2 and 3C are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23.

Latent Epstein-Barr virus (EBV) infection and growth transformation of B lymphocytes is characterized by EBV nuclear and membrane protein expression (EBV nuclear antigen [EBNA] and latent membrane protein [LMP], respectively). LMP1 is known to be an oncogene in rodent fibroblasts and to induce B-lymphocyte activation and cellular adhesion molecules in the EBV-negative Burkitt's lymphoma cell line Louckes. EBNA-2 is required for EBV-induced growth transformation; it lowers rodent fibroblast serum dependence and specifically induces the B-lymphocyte activation antigen CD23 in Louckes cells. These initial observations are now extended through an expanded study of EBNA- and LMP1-induced phenotypic effects in a different EBV-negative B-lymphoma cell line, BJAB. LMP1 effects were also evaluated in the EBV-negative B-lymphoma cell line BL41 and the EBV-positive Burkitt's lymphoma cell line, Daudi (Daudi is deleted for EBNA-2 and does not express LMP). Previously described EBNA-2- and LMP1-transfected Louckes cells were studied in parallel. EBNA-2, from EBV-1 strains but not EBV-2, induced CD23 and CD21 expression in transfected BJAB cells. In contrast, EBNA-3C induced CD21 but not CD23, while no changes were evident in vector control-, EBNA-1-, or EBNA-LP-transfected clones. EBNAs did not affect CD10, CD30, CD39, CD40, CD44, or cellular adhesion molecules. LMP1 expression in all cell lines induced growth in large clumps and expression of the cellular adhesion molecules ICAM-1, LFA-1, and LFA-3 in those cell lines which constitutively express low levels. LMP1 expression induced marked homotypic adhesion in the BJAB cell line, despite the fact that there was no significant increase in the high constitutive BJAB LFA-1 and ICAM-1 levels, suggesting that LMP1 also induces an associated functional change in these molecules. LMP1 induction of these cellular adhesion molecules was also associated with increased heterotypic adhesion to T lymphocytes. The Burkitt's lymphoma marker, CALLA (CD10), was uniformly down regulated by LMP1 in all cell lines. In contrast, LMP1 induced unique profiles of B-lymphocyte activation antigens in the various cell lines. LMP1 induced CD23 and CD39 in BJAB; CD23 in Louckes; CD39 and CD40 in BL41; and CD21, CD40, and CD44 in Daudi. In BJAB, CD23 surface and mRNA expression were markedly increased by EBNA-2 and LMP1 coexpression, compared with EBNA-2 or LMP1 alone. This cooperative effect was CD23 specific, since no such effect was observed on another marker, CD21.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, CD↗

Epstein-Barr virus nuclear antigen 2 transactivates latent membrane protein LMP1.

Several lines of evidence are compatible with the hypothesis that Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA-2) or leader protein (EBNA-LP) affects expression of the EBV latent infection membrane protein LMP1. We now demonstrate the following. (i) Acute transfection and expression of EBNA-2 under control of simian virus 40 or Moloney murine leukemia virus promoters resulted in increased LMP1 expression in P3HR-1-infected Burkitt's lymphoma cells and the P3HR-1 or Daudi cell line. (ii) Transfection and expression of EBNA-LP alone had no effect on LMP1 expression and did not act synergistically with EBNA-2 to affect LMP1 expression. (iii) LMP1 expression in Daudi and P3HR-1-infected cells was controlled at the mRNA level, and EBNA-2 expression in Daudi cells increased LMP1 mRNA. (iv) No other EBV genes were required for EBNA-2 transactivation of LMP1 since cotransfection of recombinant EBNA-2 expression vectors and genomic LMP1 DNA fragments enhanced LMP1 expression in the EBV-negative B-lymphoma cell lines BJAB, Louckes, and BL30. (v) An EBNA-2-responsive element was found within the -512 to +40 LMP1 DNA since this DNA linked to a chloramphenicol acetyltransferase reporter gene was transactivated by cotransfection with an EBNA-2 expression vector. (vi) The EBV type 2 EBNA-2 transactivated LMP1 as well as the EBV type 1 EBNA-2. (vii) Two deletions within the EBNA-2 gene which rendered EBV transformation incompetent did not transactivate LMP1, whereas a transformation-competent EBNA-2 deletion mutant did transactivate LMP1. LMP1 is a potent effector of B-lymphocyte activation and can act synergistically with EBNA-2 to induce cellular CD23 gene expression. Thus, EBNA-2 transactivation of LMP1 amplifies the biological impact of EBNA-2 and underscores its central role in EBV-induced growth transformation.

Antigens, Viral↗

The histopathological pattern of primary IgA nephropathy in a Malaysian patient population.

In the 10-year period from October 1977 to July 1987, 149 cases of primary IgA nephropathy were histologically confirmed through renal biopsies in the Department of Pathology, University Hospital, Kuala Lumpur. The ages of these patients ranged from 5 to 72 years, with the majority in the 20-30 year age group. There was no sex preponderance. The ethnic distribution showed a significant predominance of Chinese with 107 (71.8%) Chinese, 24 (16.1%) Malays, 15 (10.1%) Indians and 3 others. A wide range of renal glomerular pathology was seen, the commonest being diffuse mesangioproliferative glomerulonephritis (59.1%). Focal proliferative glomerulonephritis (14.1%) followed by minimal change glomerulonephritis (10.7%) were next in order of frequency. Immunofluorescence studies consistently demonstrated heavy and predominant IgA deposition in the mesangium. Weak deposition of C3, IgG and IgM were also observed in various combinations.

Adolescent↗

Plasma gamma-aminobutyric acid in experimental fulminant hepatic failure of rats and its diagnostic value in hepatic encephalopathy.

The plasma concentration of gamma-aminobutyric acid (GABA) was measured by radioreceptor assay in galactosamine (GalN)-induced Wistar rat model of fulminant hepatic failure (FHF). The results of sequential observations in 10 FHF rats showed that the plasma GABA concentration doubled 24 hours after GalN injection, while there was no obvious clinical evidence of hepatic encephalopathy (HE). In overt HE 48 hours after the administration of GalN, the plasma concentration of GABA reached the peak value of 9,744 +/- 1,661 pmol/ml, which was 12 times as high as that before GalN injection. The consciousness, plasma concentration of GABA and SGPT activity became normal 120 hours after GalN injection. It is suggested that determination of plasma concentration of GABA is of value in the diagnosis of HE.

Alanine Transaminase↗

[Changes in bile composition in rabbits infected with Clonorchis sinensis].

This article presents the changes in the concentration of bilirubin, cholesterol, phospholipid, bile acid and the activity of bacterial beta-glucuronidase in hepatic bile of rabbits infected with metacercariae of Clonorchis sinensis. We found that the activity of bacterial beta-glucuronidase was significantly higher in the infected group (52.6 +/- 31.6 u/dl) than that in control rabbits (12.5 +/- 20.5 u/dl) (P less than 0.001), and no marked changes in the concentration of bilirubin, cholesterol, phospholipid and bile acid were found. concentration of bilirubin, cholesterol, phospholipid and bile acid were found. By using alcian blue-PAS combined stain method the authors also noticed that the amount of glycoprotein in goblet cells has considerably increased and secreted increasingly to the biliary duct after infection with Clonorchis sinensis. As the increase in bacterial beta-glucuronidase activity and glycoprotein in bile is in favour of the formation of pigment stone, this may explain why clonorchiasis is often complicated with cholelithiasis.

Animals↗

[Pharmacological studies of huomaisan].

After per os Huomaisan twice a day for 5 days, HMS significantly prolonged thrombus formation time and inhibited platelet aggregation induced by ADP and collagen. Meanwhile, HMS also decreased blood viscosity, but did not significantly affect hematocrit. The result shows that HMS has multiple actions on blood.

Animals↗

Tetraphenylborate potentiates the respiratory inhibition by the dopaminergic neurotoxin MPP+ in both electron transport particles and intact mitochondria.

The cytotoxicity of 1-methyl-4-phenylpyridinium (MPP+) is believed to arise as a consequence of its time- and energy-dependent accumulation inside mitochondria, followed by inhibition of electron transport at Complex I of the respiratory chain. Consistent with our proposal that the accumulation of MPP+ represents a passive Nernstian transport into mitochondria in response to the transmembrane electrochemical potential gradient, tetraphenylborate (TPB-) was found to accelerate the onset of the respiratory inhibition by MPP+ on intact mitochondria. Moreover, the ultimate level of inhibition reached was unexpectedly also increased. The latter is now explained by our finding that TPB- elicits a 12-fold enhancement of MPP+ inhibition of respiration in electron transport particles. It is suggested that TPB- facilitates access of MPP+ to its intramembrane site of inhibitory action in Complex I.

1-Methyl-4-phenylpyridinium↗

Fracture behavior of urinary stones under compression.

The fracture behavior of two types of urinary stones, namely struvite and calcium oxalate, during compression testing was studied. Scanning electron microscopy (SEM) was used to characterize the fracture surfaces. Both types of stone showed pseudo-plastic behavior as indicated by their load-displacement curve. The onset of nonlinear behavior was found to correspond to development of microcracks in the specimens. The compressive strength was defined as the stress calculated at the maximum load. In struvite samples, the maximum load corresponded with the development of large cracks parallel to the compressive axis. For oxalate stones a separation of the outer layer (crust) from the inner layer (core) marked the point of maximum load. The compressive strength of the struvite samples was found to depend on the orientation of lamellae relative to the loading axis. Struvite stones, when loaded parallel to the lamination direction showed a higher compressive strength than oxalate stones did. The fracture behavior and compressive strength of a model material (z-brick) were also characterized and compared to those of the urinary stones.

Lithotripsy↗