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Biomedical subjects

J F Wang

Publications and source records attributed to J F Wang.

At least 73 records · Page 4Linked to original sources
PubMed1999

Expression and utilization of co-receptors in HIV and simian immunodeficiency virus infection of megakaryocytes.

OBJECTIVE: To analyse the expression and specificity of co-receptors for the entry of HIV and simian immunodeficiency virus (SIV) into megakaryocytes. DESIGN AND METHODS: The expression of co-receptors was determined by flow cytometric analysis in combination with reverse transcription-polymerase chain (RT-PCR) reaction. The specificity of co-receptors in virus entry was determined by the infection of HIV-1 pseudotyped with X4- (HXB2), R5- (YU2), or R5X4-tropic (89.6) envelope proteins of HIV-1 or with envelope proteins of SIVpbj1.9. RESULTS: The model human erythroleukemia (HEL) cell line, exhibiting megakaryocytic-like properties, expressed CCR5, CCR3, CXCR4, and CPR15/BOB, and all viruses except YU2 (R5) efficiently entered the cells. The blocking of virus entry with specific chemokines showed that the entry of HXB2 (X4) was impaired by SDF-1beta but not by other chemokines, indicating that CXCR4 was a major co-receptor for the entry of HXB2. Primary human bone marrow megakaryocytes displayed a different repertoire of co-receptor expression from that of HEL cells, as all viruses except YU2 efficiently entered these cells. However, chemokine blocking experiments showed that the entry of HXB2 into primary bone marrow megakaryocytes was insufficiently blocked by SDF-1beta compared with the entry into HEL cells, suggesting that alternative co-receptors could be employed for the entry of X4 virus into bone marrow cells. CONCLUSION: These data suggest that cells of megakaryocytic lineage are susceptible to infection by X4 viruses, with less marked susceptibility to R5 isolates, and that SDF-1beta efficiently blocks the infection of HEL cells but not of primary bone marrow megakaryocytes. Our data reveal that novel co-receptors are probably utilized for the entry of X4 virus into megakaryocytes.

Animals↗
PubMed1999

Lithium and valproate differentially regulate brain regional expression of phosphorylated CREB and c-Fos.

Previous studies in our laboratory have shown that the mood stabilizers, lithium and valproate (VPA), regulate the transcription factors, cyclic AMP responsive element binding protein (CREB), c-Fos and c-Jun, differentially in cultured human neuroblastoma SH-SY5Y cells. Here, we confirm these findings in rat brain and further study the brain-regional effects of these drugs using immunohistochemistry. We found that although chronic treatment with LiCl or VPA did not change the expression of c-Fos and c-Jun, acute treatment with either drugs increased c-Fos expression but not c-Jun expression in CA1 and CA3 regions of hippocampus. Chronic treatment with LiCl, but not VPA, decreased CREB phosphorylation in rat cerebral cortex and hippocampus. These results suggest that lithium and VPA may act on different pathways to bring about their long-term prophylactic effects on bipolar disorder (BD). The regulation of CREB phosphorylation may be relevant to lithium effect. VPA, which is also effective in BD, may be linked to other pathways.

Animals↗
PubMed1999

Identification of a novel lithium regulated gene in rat brain.

Differential display PCR was used to identify genes regulated by mood stabilizer lithium in rat cerebral cortex. A differentially displayed lithium regulated gene fragment was isolated in rat cerebral cortex after chronic treatment with lithium (1.69 g/kg, p.o. ) for three weeks. A 1216-nucleotide cDNA for a novel lithium regulated gene (NLRG) was isolated from a rat brain cDNA library with RACE (rapid amplification of 5' cDNA end) PCR using a prime from the differentially displayed NLRG gene fragment. The deduced protein sequence was 321 amino acids long, and shows a significant homology with yeast nitrogen permease regulator 2 (NPR2). NLRG expression induced by lithium was confirmed by Northern and slot blot analysis in rat cerebral cortex and neuroblastomaxglioma NG108-15 cells, respectively. In situ hybridization revealed that chronic treatment with lithium increased NLRG gene expression in frontal cortex and hippocampus, but not in striatum, hypothalamus and thalamus regions of rat brain. These results suggest a novel target for lithium which may be relevant to its mechanism of action.

Amino Acid Sequence↗
PubMed1999

Polyneuropathy with osmiophilic membrane-bound, cytoplasmic inclusions in Schwann cells (POMCIS).

In the cytoplasm of Schwann cells of a sural nerve biopsy from a 21-year-old female patient with chronic neuropathy we noted numerous unique, usually double membrane-bound, osmiophilic, granular or globular inclusions, approximately 30-600 microm in diameter. Some of these membrane-bound vesicular or tubular structures contained less dense or no osmiophilic inclusions. Morphometry revealed a reduction of the myelin area per endoneural area to approximately 13% (normal value: 20- 30%) and of the density of myelinated nerve fibers to 5,412/mm(2) (normal value at this age: 6,000-9,000/mm(2)). Large myelinated nerve fibers were predominantly reduced in number, and no myelinated nerve fibers with diameters larger than 4.5 microm were seen. Numerous, usually small onion bulb formations indicated a predominantly demyelinating type of neuropathy. This is to the best of our knowledge the first case of a chronic demyelinating neuropathy in which this kind of presumably pathognostic deposits in the cytoplasm of Schwann cells was detected.

Adult↗
PubMed1999

Solution conformation of brazzein by 1H nuclear magnetic resonance: resonance assignment and secondary structure.

Brazzein is a sweet-tasting protein isolated from the fruit of the West African plant Pentadiplandra brazzeana Baillon. It is the smallest and the most water-soluble sweet protein discovered so far, it is also highly thermostable. The proton NMR study of brazzein at 600 MHz (pH 3.5, 300K) is presented. Complete sequence specific assignment of the individual backbone and sidechain proton resonances were achieved using through-bond and through-space connectivities obtained from standard two-dimensional NMR techniques. The secondary structure of brazzein contains one alpha-helix (residues 21-29), one short 3(10)-helix (residues 14-17), two strands of antiparallel beta-sheet (residues 34-39, 44-50) and probably a third strand (residues 5-7) near the N-terminus.

Amino Acid Sequence↗
PubMed1999

Cyclic AMP responsive element binding protein phosphorylation and DNA binding is decreased by chronic lithium but not valproate treatment of SH-SY5Y neuroblastoma cells.

Mood stabilizing drugs decrease central nervous system cyclic AMP signaling. We report here that chronic, but not acute treatment with lithium chloride in human neuroblastoma SH-SY5Y cells, inhibits phosphorylation of cyclic AMP responsive element binding protein and cyclic AMP responsive element DNA binding induced by the adenylyl cyclase activator forskolin, but has no effect on constitutive expression of cyclic AMP responsive element binding protein. These results are consistent with an effect of lithium to blunt the cyclic AMP signal transduction pathway. Such an effect is not shared by the other commonly prescribed mood stabilizer, sodium valproate. Our results suggest that cyclic AMP responsive element binding protein regulated gene expression may be relevant to the long-term prophylactic effect of lithium. Furthermore, sodium valproate, which is also effective in bipolar disorder, would appear to act on other pathways to bring about its therapeutic effects.

Adenylyl Cyclases↗
PubMed1999

Correlation of muscle fiber type measurements with clinical and molecular genetic data in Duchenne muscular dystrophy.

Clinical improvement following surgery in patients with Duchenne muscular dystrophy (DMD) may be influenced by the severity of muscle fiber damage. This study correlates morphometric alterations of muscle fiber types, severity of fat tissue proliferation and fibrosis with Western blots, multiplex polymerase chain reaction (PCR), and postoperative state in DMD. The main results of this study show that the mean diameter of type 2 fibers is usually markedly larger than that of type I fibers in DMD although the number of type 2 fibers is severely reduced. The mean percentage of the remaining type 1 fibers was in the range of 57-82%. The morphometric and histopathological results were in agreement with the clinically estimated postoperative state, especially in the patients who presented a severe state or suggestive clinical improvement. It is concluded that combination of both quantitative and qualitative evaluation of muscle biopsies is suitable for better evaluation of the postoperative state in patients with DMD, whereas severity of exon deletions correlated poorly with morphometry and postoperative clinical state.

Adolescent↗
PubMed1999

G Protein-coupled cyclic AMP signaling in postmortem brain of subjects with mood disorders: effects of diagnosis, suicide, and treatment at the time of death.

Components of cyclic AMP (cAMP) signaling were examined in postmortem cerebral cortex of a well characterized group of patients with mood disorders and nonpsychiatric control subjects. We measured G protein levels, adenylyl cyclase (AC) activity, and CREB levels in cerebral cortex of the subjects with respect to diagnosis, treatment, and suicide. There was no effect of diagnosis on any measure, except for a trend toward decreased stimulated AC activity in subjects with mood disorders relative to control subjects. We also detected a significant effect of suicide on temporal cortex CREB levels in subjects that died as a result of suicide relative to those that did not, which was more evident in patients with major depressive disorder. Bipolar disorder (BD) subjects treated with anticonvulsants at the time of death had decreased temporal cortex CREB levels relative to those not receiving anticonvulsants. Furthermore, we found a trend toward decreased occipital cortex G alpha(s) (short) levels in BD subjects treated with lithium. These results support the hypothesis of altered cAMP signaling in mood disorders and raise the possibility that factors other than diagnosis, such as treatment and suicide, may be relevant to cell-signaling abnormalities reported in the literature.

Adenylyl Cyclases↗
PubMed1999

Differential depressant effects of general anesthetics on the cardiovascular response to cocaine in mice.

In recent years, murine models have gained increasing importance for studies of cardiovascular physiology and pharmacology, largely due to the development of transgenic strains with specific alterations in phenotype. Differential effects of general anesthetic agents on the cardiovascular responses to cocaine have been reported in larger mammals; therefore, we studied the effects of commonly used anesthetics on heart function and on blood pressure responses to cocaine in Swiss Webster mice. We positioned a polyethylene catheter (PE-10) in the right carotid artery or left ventricle of mice anesthetized with equivalent anesthetic dose of either ketamine-xylazine (KX, 40 mg/kg + 5 mg/kg), pentobarbital (PEN, 40 mg/kg) or alpha-chloralose-urethane (CU, 80 mg/kg + 100 mg/kg). Cocaine (0.3 mg/kg, 1 mg/kg and 3 mg/kg) was administrated via the left jugular vein by bolus injection. In the KX group, the basal mean arterial pressure (MAP) and systolic left ventricular pressure (LVP) were 110 +/- 12 and 120 +/- 13 mmHg, respectively, close to conscious values. However, PEN and CU significantly decreased the basal parameters (P < 0.01 compared to the KX group). The lowest dose of cocaine (0.3 mg/kg) elicited minimal changes. Significant responses were obtained with a 1-mg/kg dose of cocaine (P < 0.01 compared to baseline). However, at 3 mg/kg, a toxic effect of cocaine appeared in all three anesthetic groups. Compared to published conscious animal data, anesthetic agents attenuated the cardiovascular effects of cocaine. Taken together, our results indicate that minimally effective doses of general anesthetics may significantly alter the basal hemodynamic state and the responses to sympathomimetic agents in the murine model, as has been reported in larger mammalian species. We concluded that anesthesia with ketamine-xylazine provides baseline hemodynamic values close to reported values in conscious animals, but also attenuates the hemodynamic response to cocaine.

Anesthetics, General↗
PubMed1999

An agonist anti-human CD40 monoclonal antibody that induces dendritic cell formation and maturation and inhibits proliferation of a myeloma cell line.

CD40, a 48-50 KD cell membrane molecule, member of the nerve growth factor receptor and tumor necrosis factor receptor superfamily, is an important costimulatory molecule during the immune response. Anti-CD40 monoclonal antibody (MAb) has been shown earlier to costimulate with IgM or phorbol esters resting B cells to proliferate, differentiate, secrete immunoglobulins, and switch isotype. Here we report on an agonistic mouse anti-human CD40 MAb 5C11. The specificity of this MAb was verified by flow cytometry, Western blotting, and competition with anti-CD40 MAb 89. We studied the effects of MAb 5C11 on a multimyeloma cell line, XG2, that expresses the CD40 antigen strongly and found that this MAb caused the homotypic aggregation of XG2, strongly suppressed XG2 proliferation, and led to its apoptosis after 24 hr of treatment. Interestingly, MAb 5C11 also triggered the generation, proliferation, and maturation of dendritic cells from peripheral blood monocytes, either by itself or in combination with GM-CSF and IL-4.

Animals↗
PubMed1999

Verification of the Health-Related Hardiness Scale: cross-cultural analysis.

The article describes data collected using Pollock's Health-Related Hardiness Scale (HRHS) in two cultural groups of nurses. The purposes of the study were to verify the workability of the HRHS cross-culturally and to compare the effects of health hardiness in nurses in the United States and Taiwan. A total of 163 American and 615 Taiwanese nurses participated and answered a self-administered questionnaire by using Pollock's 34-item HRHS. Psychometric analyses identified two factors of hardiness that are different from Pollock's factors. Pollock's findings were verified, and the HRHS is valid for measuring hardiness constructs as exemplified by the strong factor loading obtained from this study, which ranged from 0.43 to 0.68 for American nurses and 0.47 to 0.68 for Taiwanese nurses.

Adaptation, Psychological↗
PubMed1999

Autosomal dominant burning feet syndrome.

Familial burning feet syndrome inherited as an autosomal dominant trait has been described in only one family. Due to an associated sensory neuropathy the autosomal dominant burning feet syndrome was suggested to represent a variant form of hereditary sensory and autonomic neuropathy type I (HSAN I). Clinical, histopathological, and molecular genetic studies were performed in a large German kindred with autosomal dominant burning feet syndrome. The autosomal dominant burning feet syndrome was associated with a neuropathy predominantly affecting small unmyelinated nerve fibres. Linkage to the HSAN I locus on chromosome 9q22 and to the Charcot-Marie-Tooth disease type 2B (CMT 2B) locus on chromosome 3q13-q22 was excluded. The autosomal dominant burning feet syndrome is neither allelic to HSAN I nor to CMT 2B and thus represents a distinct genetic entity.

Female↗
PubMed1999

Platelet protein kinase C alpha levels in drug-free and lithium-treated subjects with bipolar disorder.

Recent studies suggest that protein kinase C (PKC), particularly the alpha isoform, plays an important role in the action of lithium. There is, however, little evidence from patients with bipolar disorder (BD) to support this effect. The present investigation carried out comparative studies of PKC levels in platelets obtained from BD subjects including those with and without lithium treatment. All subjects met DSM-IV criteria for BD type I confirmed by structured interview (SCID-IV). Levels of PKC-alpha isoform in platelets from controls and from BD subjects were measured with immunoblotting analysis. No significant differences were found between controls, drug-free or lithium-treated BD subjects on membrane or cytosolic levels of PKC-alpha or in the membrane-to-cytosol ratio of this protein. The present study suggests that levels of PKC-alpha do not change in the peripheral tissues of BD subjects with or without lithium treatment.

Adult↗
PubMed1999

Differential display PCR reveals novel targets for the mood-stabilizing drug valproate including the molecular chaperone GRP78.

Differential display polymerase chain reaction was used to identify genes regulated by the mood-stabilizing drug valproate (VPA). Four differentially displayed valproate-regulated gene fragments were isolated in rat cerebral cortex after i.p. injection of sodium VPA (300 mg/kg) for 3 weeks, and their expression was confirmed by Northern and slot blot analysis in rat cerebral cortex and C6 glioma cells. Sequencing analysis revealed three previously unidentified cDNA fragments in addition to a sequence with 100% homology with a molecular chaperone, 78-kDa glucose-regulated protein (GRP78). VPA treatment did not increase mRNA expression of 70-kDa heat shock protein, which is a related stress-induced molecular chaperone protein. All four candidate genes, including GRP78, showed similar VPA concentration-dependent increases in mRNA abundance. Another commonly prescribed mood-stabilizing anticonvulsant, carbamazepine, also increased GRP78 mRNA expression in C6 glioma cells, whereas lithium had no effect at doses up to 2 mM. Immunoblotting revealed that GRP78 protein levels were also increased in C6 glioma cells treated with VPA under the same conditions. Nuclear runoff analysis showed that VPA increased GRP78 gene transcription. Because GRP78 possesses molecular chaperone activity, binds Ca2+ in the endoplasmic reticulum, and protects cells from the deleterious effects of damaged proteins, the present findings suggest that VPA (and possibly carbamazepine) treatment may target one or more of these processes.

Animals↗
PubMed1999

Ethanol inhibits lung clearance of Pseudomonas aeruginosa by a neutrophil and nitric oxide-dependent mechanism, in vivo.

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen that can be found in individuals in which the immune system has been suppressed by HIV/AIDS or chronic alcoholism. We evaluated the role of inducible nitric oxide synthase (NOS II) as a modulator of lung concentrations of P. aeruginosa in normal rats and rats given a single dose of ethanol (ETOH). Rats were pretreated with either sterile saline (PBS, 0.1 ml/kg, i.v.) or the NOS II inhibitor L-N6-iminoethyl lysine (LNIL, 10 mg/kg, i.v.) 15 min before intraperitoneal administration of either PBS (4.5 ml/kg) or ETOH (4.5 g/kg). Thirty min after administration of PBS or ETOH the rats were placed in inhalation chambers and exposed to 45 min of an aerosol containing P. aeruginosa (5 x 10(4) colony forming units, CFU). A group of rats (n = 5-6/treatment/time period) were killed immediately (0 hr) or 4 hr after inhalation of P. aeruginosa. The lungs were homogenized and the P. aeruginosa were grown in nutrient broth to determine the number of viable CFU remaining in the lung. The NOS II and TNFalpha mRNA and protein content lung alveolar macrophages (AM) and neutrophils (PMN) were measured with RT-PCR and Western blot. The concentration of nitrate and nitrite anion in the bronchoalveolar lavage fluid (BALf) and ex vivo incubates of PMN were also measured. The CFU of P. aeruginosa present in the lungs of the four groups of rats at 0 hr did not differ. The CFU of P. aeruginosa in the lung increased (p < 0.05) in rats pretreated with ETOH when compared with that obtained from rats pretreated with PBS. However, pretreatment of rats with LNIL decreased (p < 0.05) the 4 hr lung content of P. aeruginosa. Coadministration of LNIL and ETOH to rats augmented the CFU of P. aeruginosa in lungs to amounts which did not differ from that of rats pretreated with ETOH. Inhalation of P. aeruginosa increased NOS II mRNA and protein in rat AM and PMN. Pretreatment of rats with ETOH alone, or in combination with LNIL, inhibited P. aeruginosa-induced NOS II transcription and translation and AM and PMN nitrate and nitrite generation whereas pretreatment with LNIL alone only inhibited nitrate and nitrite generation. Pretreatment of rats with ETOH suppressed P. aeruginosa stimulated PMN recruitment into the lung whereas LNIL enhanced (p < 0.05) P. aeruginosa-stimulated PMN recruitment into the lung. ETOH-induced increases of the lung content of P. aeruginosa were associated with increased PKC delta isozyme in the membrane of the PMN but could not be explained by altered plasma concentrations of hydrocortisone or ETOH. The data demonstrate that selective inhibition of NOS II-derived NO by LNIL decreases the lung content of P. aeruginosa whereas ETOH inhibits the lung clearance of P. aeruginosa. Speculatively, the difference between these effects of LNIL and ETOH may result from differences in drug-induced changes in lung recruitment of PMN.

Animals↗
PubMed1998

Stromal cell-derived factor-1 alpha and stem cell factor/kit ligand share signaling pathways in hemopoietic progenitors: a potential mechanism for cooperative induction of chemotaxis.

Stromal cell-derived factor (SDF-1alpha), the ligand for CXCR4, is a chemokine that acts as a potent chemoattractant for hemopoietic progenitor cells. Stem cell factor/kit ligand (SCF/KL), an early acting cytokine, has recently been reported to enhance the chemotaxis induced by SDF-1alpha. However, very little is known about downstream signaling events following these receptor-ligand interactions. To investigate these events, we utilized a model progenitor cell line, CTS, which expresses both the CXCR4 and c-kit receptors. We observed strong Ca2+ mobilization and enhancement of chemotaxis following treatment with SDF-1alpha or SCF/KL. A combination of these factors enhanced this chemotaxis in CTS cells as well as in CD34+ bone marrow cells. Prior treatment of CTS cells with pertussis toxin inhibited the SDF-1alpha-induced chemotaxis, suggesting that SDF-1alpha signaling involves a pertussis-sensitive Gi-coupled protein. SDF-1alpha treatment resulted in a rapid phosphorylation of the focal adhesion molecules RAFTK (related adhesion focal tyrosine kinase), paxillin, and p130cas, which then declined within minutes. SCF/KL alone or in combination with SDF-1alpha induced a rapid and sustained effect on phosphorylation of these substrates. SDF-1alpha treatment resulted in a rapid and robust activation of p44/42 mitogen-activated protein kinase compared with the relatively weak and delayed effect of SCF/KL treatment. Interestingly, a delayed but sustained activation of mitogen-activated protein kinase activation was observed when the factors were used in combination. Such cooperativity in downstream signaling pathways may explain the enhanced chemotaxis of progenitors observed with SDF-1alpha in combination with SCF/KL.

Antigens, CD34↗