Biomedical subjects

F Wang

Publications and source records attributed to F Wang.

At least 343 records · Page 19Linked to original sources

PubMed1998

The heparan sulfate-fibroblast growth factor family: diversity of structure and function.

The fibroblast growth factor (FGF) receptor complex is a ubiquitous regulator of development and adult tissue homeostasis that bridges the peri-cellular matrix and the intracellular environment. Diverse members of the FGF polypeptide family, the FGF receptor tyrosine kinase (FGFRTK) family and the FGF receptor heparan sulfate proteoglycan (FGFRHS) family combine to result in active and specific FGFR signal transduction complexes. Regulated alternate splicing and combination of variant subdomains give rise to diversity of FGFRTK monomers. Divalent cations cooperate with the FGFRHS to conformationally restrict FGFRTK trans-phosphorylation, which causes depression of kinase activity and facilitates appropriate activation of the FGFR complex by FGF. Diffusional and conformational molecular models of the oligomeric FGFR complex are presented to explain how different point mutations in the FGFRTK commonly cause craniofacial and skeletal abnormalities of graded severity by graded increases in FGF-independent activity of total FGFR complexes. The role of the FGF family in liver growth and function and in prostate tumor progression is discussed.

Adult↗

PubMed1998

Immune modulation of human B lymphocytes by gene transfer with recombinant Epstein-Barr virus amplicons.

We described previously a novel mode of gene transfer by infection of human B lymphocytes with recombinant Epstein-Barr virus (EBV) amplicons. This system was explored for its potential use in expressing various recombinant genes, including the cytokine IL-4, the HIV envelope glycoprotein (gp120) and a suicide and gag gene. Recombinant genes were present as multiple copy episomes and stable, high level recombinant gene expression could be detected by antigenic and functional assays. Amplicon-infected B cells secreted high levels of recombinant cytokine and efficiently presented recombinant antigens through classes I and II MHC-restricted antigen processing pathways. Thus, recombinant EBV amplicons can be used to express components of the immune system or heterologous genes for immune recognition in human B cells. Combining gene transfer with EBV infection may provide unique advantages for in vitro and in vivo gene transfer.

Antigen Presentation↗

PubMed1998

The role of cytokines in the failing human heart.

Despite repeated attempts to develop a unifying hypothesis that explains the clinical syndrome of heart failure, no single conceptual paradigm has withstood the test of time. In this regard, recent studies have shown that a class of biologically active molecules, generically referred to as cytokines, are overexposed in heart failure. This article will review recent clinical and experimental material that suggest proinflammatory (stress activated) cytokines such as tumor necrosis factor-alpha (TFN-alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) may play a role in the pathogenesis of congestive heart failure. The scope of this article includes an overview of the biology of cytokines in the heart, as well as review of the clinical studies that have documented elevated levels of cytokines and cytokine receptors in patients with heart failure.

Animals↗

PubMed1998

An olfactory sensory map develops in the absence of normal projection neurons or GABAergic interneurons.

Olfactory sensory neurons expressing a given odorant receptor project to two topographically fixed glomeruli in the olfactory bulb. We have examined the contribution of different cell types in the olfactory bulb to the establishment of this topographic map. Mice with a homozygous deficiency in Tbr-1 lack most projection neurons, whereas mice with a homozygous deficiency in Dlx-1 and Dlx-2 lack most GABAergic interneurons. Mice bearing a P2-IRES-tau-lacZ allele and deficient in either Tbr-1 or Dlx-1/Dlx-2 reveal the convergence of axons to one medial and one lateral site at positions analogous to those observed in wild-type mice. These observations suggest that the establishment of a topographic map is not dependent upon cues provided by, or synapse formation with, the major neuronal cell types in the olfactory bulb.

Animals↗

PubMed1998

Comparison of the changes in protein kinase C induced by glutamate in primary cortical neurons and by in vivo cerebral ischaemia.

Changes in protein kinase C (PKC) were compared in primary cortical neurons exposed to glutamate and in the CA-1 hippocampal region of rats subjected to transient cerebral ischaemia. After a 15-min exposure of cortical neurons to excitotoxic levels of glutamate, a 50-60% loss of membrane PKC activity but only about a 20% loss in the amount of enzyme was observed, suggesting that in addition to enzyme loss other mechanisms also contributed to the overall loss of membrane PKC activity. Glutamate induced a 25-40% decrease in immunodetectable levels of PKC alpha, beta, gamma, and lambda but no detectable changes in PCK epsilon and zeta. The loss of PKC activity coincided with a shift in electrophoretic mobility of PKC gamma, epsilon, and lambda, but not of PKC alpha, beta, or zeta, suggesting post-translational modification of some PKC isoforms. By comparison, in rats subjected to transient (15-min) global ischaemia, a similar 50-60% decrease in membrane PKC activity, a 20-25% loss in the amount of PKC, and a shift in PKC mobility were observed in CA-1 neurons 6 h post-reperfusion. In both the in vivo and the in vitro "ischaemic" models, administration of the AMPA receptor antagonist NBQX prevented the loss of PKC activity. These results indicate that the loss of PKC observed in in vivo ischaemia is likely to be due to excitotoxic damage and that this event can be closely mirrored in primary neuronal cultures damaged by glutamate.

Animals↗

PubMed1998

Glycosphingolipid composition of MDA-MB-231 and MCF-7 human breast cancer cell lines.

Much evidence has shown that glycosphingolipids are involved in cellular recognition, regulation of cell growth, and metastasis. In the present study, the major glycosphingolipids of two widely studied human breast cancer cell lines were examined. The MCF-7 cell line has functional estrogen and EGF receptors, is dependent on estrogen and EGF for growth, and is uninvasive, while MDA-MB-231 cells are a model for more aggressive, hormone-independent breast cancer. There was twice as much neutral glycolipid in MCF-7 cells as in MDA-MB-231 cells. The major neutral glycolipids in MDA-MB-231 cells were identified as CTH and globoside. MCF-7 cells also contained as the major neutral glycolipids CTH as well as globoside and two other glycolipids which were tentatively identified as galactosylgloboside and fucosylgalactosylgloboside by exoglycosidase treatments. Conversely, the ganglioside content was four fold higher in MDA-MB-231 cells compared to MCF-7 cells. The abundant gangliosides in both cell lines were GM3, GM2, GM1, and GD1a. A minor monosialoganglioside was detected in MDA-MB-231 cells. The striking 18 fold greater amount of GM3 in MDA-MB-231 cells may have important implications because GM3 has been suggested to be involved in regulation of growth factor functions. In agreement, insertion of ganglioside GM3 into the plasma membrane of MCF-7 cells blocked the growth stimulatory effect of EGF.

Breast Neoplasms↗

PubMed1998

Myasthenia gravis without chronic GVHD after allogeneic bone marrow transplantation.

A 20-year-old man with aplastic anemia developed myasthenia gravis (MG) 7 months after bone marrow transplantation (BMT) from an HLA one locus-mismatched sister. Proximal muscle weakness (predominant in the lower limbs) and dysphagia occurred without any other sign of graft-versus-host disease (GVHD), 1 month after cessation of immunosuppression with cyclosporine. The diagnosis of MG was based on clinical symptoms and on neurophysiologic investigations showing a significant increase of the Jitter in single-fiber electromyography and a significant decremental response during repetitive stimulation at slow rates, but antibodies against the acetylcholine receptor (AchRab) were negative. All clinical and neurophysiological signs normalized within 1 month of treatment with low-dose prednisolone and pyridostigmine, and the patient is perfectly well 1 year after cessation of all therapy. All cases of BMT-associated MG previously published are reviewed in comparison with ours. The originality of this new observation is that this case is the only one not associated with chronic GVHD and negative for AchRab. Alternatively, MG may have been the sole manifestation of chronic GVHD in this patient.

Adult↗

PubMed1998

Human myeloma cells shed the interleukin-6 receptor: inhibition by tissue inhibitor of metalloproteinase-3 and a hydroxamate-based metalloproteinase inhibitor.

Interleukin-6 (IL-6) is the major growth factor for human myeloma cells, exerting its effect through the IL-6 receptor (IL-6R). A soluble form of IL-6R (sIL-6R) has been identified, which increases the sensitivity of myeloma cells to IL-6. In patients with multiple myeloma (MM), serum concentrations of sIL-6R are elevated and associated with poor prognosis. The present study was undertaken to determine whether proteolytic cleavage of IL-6R could contribute to sIL-6R release from human myeloma cells, and also to identify the class of proteinase responsible for this event. Human myeloma cell lines were shown to express IL-6R upon their surface and also to release sIL-6R into culture supernatants. In addition, phorbol 12-myristate 13-acetate (PMA) stimulated a loss of IL-6R from the cell surface, with a corresponding increase in the concentration of sIL-6R in the supernatant. Inhibitors of serine and cysteine proteinases, and tissue inhibitor of metalloproteinase (TIMP) -1 and TIMP-2, were shown to have no effect on the magnitude of sIL-6R release. In contrast, TIMP-3 and a hydroxamate-based metalloproteinase inhibitor (BB-94), inhibited both constitutive and PMA-induced release of sIL-6R. Myeloma cells freshly isolated from the bone marrow of a patient with MM were also shown to express IL-6R upon their surface, and to shed this receptor in response to PMA. These data demonstrate that increased proteolytic cleavage of IL-6R, mediated by a non-matrix-type metalloproteinase, is likely to contribute to the elevated concentrations of sIL-6R found in the serum of patients with MM. Inhibition of sIL-6R release by hydroxamate-based metalloproteinase inhibitors may represent a novel therapeutic approach to the treatment of MM.

Bone Marrow Cells↗

PubMed1998

Flexural strength of a provisional resin material with fibre addition.

The effect of fibre addition on the flexural strength of a resin was studied. A provisional material (ALIKE; GC America Inc.) was used as the control and resinous matrix. Silane treated glass fibre was selected for the reinforcing treatment. In order to determine the geometric influence on the strength, ordered fibres (1 w/o) were immersed within a resinous matrix in four different locations. In addition, randomly dispersed fibres, 5 mm in length, were blended at 1 w/o up to 8 w/o with acrylic powder and moulded into rectangular specimens (34 mm x 9 mm x 8 mm) with P:L = 2:1. Ten specimens were prepared for each group. A three-point flexural test was run using a span of 25 mm at a rate of 5 mm/min. The strength values were collected and analysed with ANOVA and Scheffe tests. The strengths of the specimens with orientated fibre addition ranged from 49.4 (s.d. = 5.7) to 64.5 (6.7) MPa and the control was 54.3 (4.0) MPa. In the dispersed groups, the strengths obtained ranged from 55.9 (5.9) to 87.3 (7.9) MPa. The results disclosed that inclusion of orientated fibres horizontally on the tension side of the specimens significantly improved the flexural strength compared with the control (P < 0.05). An optimal strength was obtained in the group of provisional resin containing 5 w/o dispersed fibre. Incorporation of glass fibres significantly improved the flexural strength of the resin and the dispersed method is more efficient than the orientated inclusion method.

Acrylic Resins↗

PubMed1998

Evaluation of screening schemes for eye disease in a primary care setting.

BACKGROUND AND PURPOSE: Screening in a primary care setting could be an effective method for detection of eye disease. This study was designed to evaluate a questionnaire and a battery of tests for their performance in eye disease screening at a primary care clinic. METHODS: 405 patients aged 40 years or older were interviewed and received a comprehensive eye examination including visual acuity and visual field testing, tonometry, slit-lamp examination, dilated fundus examination and photography. Sensitivity and specificity for the identification of eye disease were calculated for each test and various combinations of tests. RESULTS: A questionnaire-based algorithm for detection of overall eye disease was sufficiently sensitive (90%) but less specific (44%) than an ideal screening test. Distance visual acuity with presenting correction of < or = 20/40 had a sensitivity of 61% and specificity of 72%. A dilated fundus examination had a sensitivity of 79% and specificity of 82%. In screening for glaucoma, tonometry was ineffective (sensitivity = 27% and specificity = 96%), while visual field testing by suprathreshold screening had a sensitivity of 70% and specificity of 67%. Among a variety of combinations, a two-stage strategy with the questionnaire as a first-stage and visual acuity and ophthalmoscopy as second-stage tests provided the best balance of sensitivity (83%) and specificity (76%). CONCLUSION: Among currently available ophthalmic tests, an eye examination including a thorough fundus examination is critical in detection of eye disease. A five-item questionnaire may be useful to identify patients at high risk in primary care practice. More effective tests are needed to improve performance of eye disease screening.

Adult↗

PubMed1998

Actions of genistein on cystic fibrosis transmembrane conductance regulator channel gating. Evidence for two binding sites with opposite effects.

Previous studies have shown that genistein increased cystic fibrosis transmembrane conductance regulator (CFTR) channel activity in the presence of saturating concentrations of forskolin and calyculin A in intact cells. Possible molecular mechanisms for genistein's action include inhibition of tyrosine kinases, inhibition of serine/threonine protein phosphatases, or direct binding of genistein to CFTR. Since genistein inhibits several enzymes that hydrolyze ATP, and ATP hydrolysis is an intrinsic property of CFTR, we examined the effect of genistein on CFTR gating in excised inside-out patches from Hi-5 insect cells and NIH3T3 cells expressing recombinant CFTR. Genistein (50 microM) did not open phosphorylated CFTR channels by itself, but increased the ATP- induced CFTR channel current by approximately twofold. A similar magnitude of enhancement was observed when genistein was applied with PKI, a specific inhibitor of protein kinase A, or vanadate, a tyrosine phosphatase inhibitor, suggesting that inhibition of protein phosphatases or tyrosine kinases does not account for genistein's effects. The enhancement of channel current increased with increasing concentrations of genistein and reached a maximum at 35 microM genistein. At higher concentrations of genistein concentration, CFTR channel current decreased, resulting in a bell-shaped dose-response relationship. In the absence of genistein, both open- and closed-time histograms could be fitted with a single exponential function, yielding a mean open time (tauO) of 0.302 +/- 0.002 s, and a mean closed time (tauC) of 0.406 +/- 0.003 s. In the presence of 50 microM genistein, the open time histogram could be fitted with a double exponential function with tauO1 = 0.429 +/- 0. 003 s and tauO2 = 2.033 +/- 0.173 s. Thus, genistein induced a prolonged open state, an effect that mimics that of nonhydrolyzable ATP analogs. Closed time analysis showed that 50 microM genistein caused a prolonged closed state with a time constant of 2.410 +/- 0.035 s. We thus conclude that (a) the effects of genistein are likely caused by a direct binding of the drug to the CFTR protein, and (b) at least two binding sites are required to explain the effects of genistein: a high affinity site that decreases the closing rate and a low affinity site that reduces the opening rate.

Adenosine Triphosphate↗

PubMed1998

Induction of type 2 deiodinase activity by cyclic guanosine 3',5'-monophosphate in cultured rat glial cells.

We investigated the effects of cyclic guanosine 3',5'-monophosphate (cGMP) on type 2 iodothyronine deiodinase (D2) in cultured rat glial cells. Rat glial cells were cultured in Dulbecco's modified Eagle's medium supplemented with 15% fetal bovine serum. When cells were cultured in the presence of 8-bromo cGMP (8-Br cGMP), an analogue of cGMP, D2 activity was increased in a time- and concentration-dependent manner. Lineweaver-Burk plots revealed that the stimulation of D2 activity by 8-Br cGMP (10(-3) M) was associated with fivefold increase in maximum velocity but without a significant change in Michaelis-Menten constant, suggesting that cGMP increases D2 activity via new enzyme synthesis. Both atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) are well known to increase the intracellular cGMP level via their guanylate cyclase-linked receptors in rat glial cells. In the present study, ANP (10(-6) M) and CNP (10(-6) M) significantly increased the D2 activity in rat glial cells (1.9-fold [ANP] or 2.3-fold [CNP] compared with control activity, respectively). Northern blot analysis demonstrated that D2 mRNA level increased in the presence of 8-Br cGMP (10(-3) M), and reached a plateau (six-fold) after 4 hours of incubation. The increment of D2 mRNA level by 8-Br cGMP was comparable with the increase of the D2 activity by this agent. Our data suggest that cGMP induces rat D2 activity, at least in part, at the pretranslational level, and that ANP and CNP increase D2 activity most likely via their guanylate cyclase-linked receptors in rat glial cells.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1998

Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane.

Phytochemicals such as indole-3-carbinol (I3C) and sulforaphane are components of cruciferous vegetables which exhibit antitumorigenic activity associated with altered carcinogen metabolism and detoxification. Diindolylmethane (DIM) is a major acid-catalyzed metabolite of I3C formed in the gut that binds to the aryl hydrocarbon receptor (AhR) and treatment of MCF-7 human breast cancer cells with 10-50 microM DIM resulted in rapid formation of the nuclear AhR complex and induction of CYP1A1 gene expression was observed at concentrations >50 microM. Previous studies have demonstrated that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a high affinity AhR ligand, inhibits 17beta-estradiol (E2)-induced responses in MCF-7 cells and growth of E2-dependent 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumors in female Sprague-Dawley rats. Results of this study show that like TCDD, DIM inhibits E2-induced proliferation of MCF-7 cells, reporter gene activity in cells transiently transfected with an E2-responsive plasmid (containing a frog vitellogenin A2 gene promoter insert) and down-regulates the nuclear estrogen receptor. Moreover, DIM (5 mg/kg every other day) also inhibits DMBA-induced mammary tumor growth in Sprague-Dawley rats and this was not accompanied by induction of hepatic CYP1A1-dependent activity. Thus, DIM represents a new class of relatively non-toxic AhR-based antiestrogens that inhibit E2-dependent tumor growth in rodents and current studies are focused on development of analogs for clinical treatment of breast cancer.

Animals↗

PubMed1998

A study of an endothelin antagonist from a Chinese anti-snake venom medicinal herb.

Because it is well known that endothelin (ET) plays an important role in the pathogenesis of cardiovascular diseases, antagonists of ET for clinical use are very important. Because ET and some snake toxins have a homologous structure and similar biologic actions the effect of Chinese anti-snake venom herbal medicines on ET bioactivity was investigated both in vivo and in vitro. Hong Bei Si Chou [Cissus assamica (Laws.) Craib] is a herbal medicine used to treat snake bite in Guangxi province. It was found that all the different fractions of EtOH extraction, the EtOAc part of the EtOH extraction, and resverotrol (3,4'5-trihydroxytransstilbene) isolated from the EtOAc part could antagonize ET both in vivo and in vitro. These three fractions transiently relaxed ET-contracted isolated rat aortic ring in a dose-dependent manner. They also antagonized the lethal effects of ET-1 in mice and inhibited blood pressure elevation induced by ET-1. The results have shown that it is possible to find ET antagonists in Chinese anti-snake venom medicinal herbs. In the future, our work should shed new light on the treatment of cardiovascular diseases in which ET is involved.

Animals↗

PubMed1998

Population and employment density functions revisited: a spatial interaction approach.

"This article proposes a generalized urban spatial structure and transportation network, and adapts the Garin-Lowry model to simulate both population and service employment densities in this hypothetical, yet realistic, city. The model is solved numerically while varying exogenous factors such as the distance friction coefficients and the spatial distribution of basic employment.... The results are generalized by estimating, via regression analysis, density functions over a large sample of simulated density patterns, pointing to the critical importance of transportation costs and basic employment distribution, and providing a basis for further empirical studies."

Demography↗

PubMed1998

Infection of human B lymphocytes with lymphocryptoviruses related to Epstein-Barr virus.

Lymphocryptoviruses (LCVs) naturally infecting Old World nonhuman primates are closely related to the human LCV, Epstein-Barr virus (EBV), and share similar genome organization and sequences, biologic properties, epidemiology, and pathogenesis. LCVs can efficiently immortalize B lymphocytes from the autologous species, but the ability of a given LCV to immortalize B cells from other Old World primate species is variable. We found that LCV from rhesus monkeys did not immortalize human B cells, and EBV did not immortalize rhesus monkey B cells. In this study, baboon LCV could not immortalize human peripheral blood B cells but could readily immortalize rhesus monkey B cells. Thus, efficient LCV-induced B-cell immortalization across distant Old World primate species appears to be restricted by a species-specific block. To further characterize this species restriction, we first cloned the rhesus monkey LCV major membrane glycoprotein and discovered that the binding epitope for the EBV receptor, CD21, was highly conserved. Stable infections of human B cells with recombinant amplicons packaged in rhesus monkey or baboon LCV envelopes were also consistent with a species-restricted block occurring after virus binding and penetration. Transient infections of human B cells with simian LCV resulted in latent LCV EBNA-2 gene expression and activation of cell CD23 gene expression. EBV-immortalized human B cells could be coinfected with baboon LCV, and the simian virus persisted and replicated in human B cells. Thus, several lines of evidence indicate that the species restriction for efficient LCV-induced B-cell immortalization occurs beyond virus binding and penetration. This has important implications for the study of LCV infection in Old World primate models and for human xenotransplantation where simian LCVs may be inadvertently introduced into humans.

Amino Acid Sequence↗

PubMed1998

Functional conservation of the transportin nuclear import pathway in divergent organisms.

Human transportin1 (hTRN1) is the nuclear import receptor for a group of pre-mRNA/mRNA-binding proteins (heterogeneous nuclear ribonucleoproteins [hnRNP]) represented by hnRNP A1, which shuttle continuously between the nucleus and the cytoplasm. hTRN1 interacts with the M9 region of hnRNP A1, a 38-amino-acid domain rich in Gly, Ser, and Asn, and mediates the nuclear import of M9-bearing proteins in vitro. Saccharomyces cerevisiae transportin (yTRN; also known as YBR017c or Kap104p) has been identified and cloned. To understanding the nuclear import mediated by yTRN, we searched with a yeast two-hybrid system for proteins that interact with it. In an exhaustive screen of the S. cerevisiae genome, the most frequently selected open reading frame was the nuclear mRNA-binding protein, Nab2p. We delineated a ca.-50-amino-acid region in Nab2p, termed NAB35, which specifically binds yTRN and is similar to the M9 motif. NAB35 also interacts with hTRN1 and functions as a nuclear localization signal in mammalian cells. Interestingly, yTRN can also mediate the import of NAB35-bearing proteins into mammalian nuclei in vitro. We also report on additional substrates for TRN as well as sequences of Drosophila melanogaster, Xenopus laevis, and Schizosaccharomyces pombe TRNs. Together, these findings demonstrate that both the M9 signal and the nuclear import machinery utilized by the transportin pathway are conserved in evolution.

Amino Acid Sequence↗

PubMed1998

A case-control study of risk factors for playground injuries among children in Kingston and area.

OBJECTIVE: To determine the risk for injury associated with environmental hazards in public playgrounds. SETTING: One hundred and seventeen playgrounds operated by municipalities or school boards in and around Kingston, Ontario, Canada. METHODS: A regional surveillance database was used to identify children presenting to emergency departments who were injured on public playgrounds; each case was individually matched (by sex, age, and month of occurrence) with two controls--one non-playground injury control, and one child seen for non-injury emergency medical care. Exposure data were obtained from an audit of playgrounds conducted using Canadian and US safety guidelines. Exposure variables included the nature of playground hazards, number of hazards, frequency of play, and total family income. No difference in odds ratios (ORs) were found using the two sets of controls, which were therefore combined for subsequent analysis. RESULTS: Multivariate analysis showed strong associations between injuries and the use of inappropriate surface materials under and around equipment (OR 21.0, 95% confidence interval (CI) 3.4 to 128.1), appropriate materials with insufficient depth (OR 18.2, 95% CI 3.3 to 99.9), and inadequate handrails or guardrails (OR 6.7, 95% CI 2.6 to 17.5). CONCLUSION: This study confirms the validity of guidelines for playground safety relating to the type and depth of surface materials and the provision of handrails and guardrails. Compliance with these guidelines is an important means of preventing injury in childhood.

Adolescent↗