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Biomedical subjects

M Wang

Publications and source records attributed to M Wang.

At least 325 records · Page 18Linked to original sources
PubMed2000

The tricornered gene, which is required for the integrity of epidermal cell extensions, encodes the Drosophila nuclear DBF2-related kinase.

During their differentiation epidermal cells of Drosophila form a rich variety of polarized structures. These include the epidermal hairs that decorate much of the adult cuticular surface, the shafts of the bristle sense organs, the lateral extensions of the arista, and the larval denticles. These cuticular structures are produced by cytoskeletal-mediated outgrowths of epidermal cells. Mutations in the tricornered gene result in the splitting or branching of all of these structures. Thus, tricornered function appears to be important for maintaining the integrity of the outgrowths. tricornered mutations however do not have major effects on the growth or shape of these cellular extensions. Inhibiting actin polymerization in differentiating cells by cytochalasin D or latrunculin A treatment also induces the splitting of hairs and bristles, suggesting that the actin cytoskeleton might be a target of tricornered. However, the drugs also result in short, fat, and occasionally malformed hairs and bristles. The data suggest that the function of the actin cytoskeleton is important for maintaining the integrity of cellular extensions as well as their growth and shape. Thus, if tricornered causes the splitting of cellular extensions by interacting with the actin cytoskeleton it likely does so in a subtle way. Consistent with this possibility we found that a weak tricornered mutant is hypersensitive to cytochalasin D. We have cloned the tricornered gene and found that it encodes the Drosophila NDR kinase. This is a conserved ser/thr protein kinase found in Caenorhabditis elegans and humans that is related to a number of kinases that have been found to be important in controlling cell structure and proliferation.

Actins↗
PubMed2000

Antioxidant LY231617 enhances electrophysiologic recovery after global cerebral ischemia in dogs.

OBJECTIVE: The potent antioxidant LY231617 (2,6-bis(1,1-dimethylethyl)-4-[[(1-ethyl)amino]methyl]phenol hydrochloride) is cytoprotective in models of focal and global cerebral ischemia. We tested the hypothesis that administration of LY231617, before the insult, would improve recovery of cerebral electrical activity and metabolic function after transient global cerebral ischemia by improving cerebral blood flow (CBF) during the reperfusion period. DESIGN: Randomized, controlled, prospective study. SETTING: Research laboratory at a university teaching hospital. SUBJECTS: Twenty-four male beagle dogs. INTERVENTIONS: All experiments were performed under pentobarbital anesthesia and controlled conditions of normoxia, normocarbia, and normothermia. Twelve control dogs received 20 mL/kg saline (vehicle) bolus into the right atrium and 0.01 mL/kg/min i.v., beginning 20 mins before 13 mins of global cerebral ischemia (by aortic occlusion). The dogs in the drug-treated group received LY231617 as a 10-mg/kg bolus 20 mins before ischemia and 5 mg/kg/hr throughout reperfusion (n = 12). CBF was measured using radiolabeled microspheres. MEASUREMENTS AND MAIN RESULTS: Total CBF, cerebral oxygen consumption, and somatosensory evoked potentials (SEP) were measured during 240 mins of reperfusion. CBF was similar in both vehicle- and LY231617-treated animals at baseline and throughout the experimental period. In all animals, SEP became isoelectric between 60 and 100 secs after cross-clamping of the ascending aorta. SEP amplitude recovery was significantly higher in drug-treated animals compared with controls (73%+/-15% vs. 39%+/-14% [mean+/-SEM] from baseline at 120 mins [p<.05] and 86%+/-12% vs. 49%+/-14% from baseline at 240 mins [p< .05]). CONCLUSIONS: LY231617 improves recovery of cerebral electrical function after complete transient global ischemia via mechanisms unrelated to cerebral circulatory effects.

Animals↗
PubMed2000

Pattern selection induced by electroconvection in the electrodeposition of iron

The morphology of iron electrodeposit is shown to relate closely to the pH of the electrolyte solution. Macroscopically, depending on the strength of the interbranch convection, which is associated with the concentration of H3O+ in the electrolyte, the deposit morphology varies from treelike pattern to meshlike pattern and dense-branching morphology. Microscopically the deposit is ramified and dense-branching at lower concentration of H3O+, while it becomes relatively smooth and stringy at higher H3O+ concentration. The symmetry of the convective vortices on the two sides of the growing tip is observed to decide the growth behavior of the tip. We suggest that H3O+ influences the pattern formation and pattern selection in the electrodeposition of iron from FeSO4 solution by either initiating interbranch convection or changing the effective interfacial energy of the deposit and the electrolyte.

Journal Article↗
PubMed2000

Crystallization and preliminary X-ray analyses of insect neurotoxins with analgesic effect from the scorpion Buthus martensii Karsch.

Three insect neurotoxins from the scorpion Buthus martensii Karsch, named BmK I1, BmK I4 and BmK I6, have been purified and crystallized. BmK I1 and BmK I4 show strong toxicity to insects, while BmK I6 is relatively weaker. They all exhibit an evident analgesic effect on mice; this is a novel biological function for scorpion insect toxins. Their crystals diffract to at least 3.5 (BmK I1), 2.8 (BmK I4), 2.8 (BmK I6 crystal form I) and 2.2 A (of BmK I6 crystal form II) resolution on an ordinary X-ray source. Crystals of BmK I1 belong to space group P6, with unit-cell parameters a = b = 66.2, c = 176.7 A. BmK I4 crystallized in the tetragonal space group I4, with unit-cell parameters a = b = 134.5, c = 60.6 A. BmK I6 has been crystallized in two forms: form I belongs to space group C2, with unit-cell parameters a = 46.5, b = 85.2, c = 32.6 A, beta = 110.5 degrees; form II belongs to space group R3, with the hexagonal unit-cell parameters a = b = 44.5, c = 164.7 A.

Amino Acid Sequence↗
PubMed2000

Structure of a new neurotoxin from the scorpion Buthus martensii Karsch at 1.76 A.

A new neurotoxin BmK M2, toxic to both mammals and insects, with the strongest toxicity in the BmK toxin series, has been purified from the Chinese scorpion Buthus martensii Karsch and crystallized with MPD at pH 7.5. The crystals are orthorhombic, belonging to space group P2(1)2(1)2(1), with unit-cell parameters a = 36.64, b = 36.95, c = 37.23 A. The structure was solved by molecular replacement and refined to R = 0.186 for all reflections to a resolution of 1.76 A. The whole sequence (64 residues) of BmK M2 was determined by crystallographic analysis based on high-resolution data and the homologous model of BmK M8. The refined BmK M2 structure shows a non-proline cis peptide bond between Pro9 and His10 which enables the C-terminal segment to adopt a conformation different to that of the weak toxin BmK M8. Recently, a mutation analysis had suggested that both the tenth residue and the C-terminus play key roles in receptor binding. Therefore, these features may be related to the binding selectivity of the group III alpha-like toxins. The charge changes of residues 8, 10, 18, 28, 55 and 59 from neutral or negative to positive or neutral, which leads to a positive electrostatic potential surface, may be responsible for the high toxicity of BmK M2.

Amino Acid Sequence↗
PubMed2000

Appropriateness of the decision to transfer nursing facility residents to the hospital.

OBJECTIVES: To develop and test a standardized instrument, the purpose of which is to assess (1) whether skilled nursing facilities (SNFs) transfer residents to emergency departments (ED) inappropriately, (2) whether residents are admitted to hospitals inappropriately, (3) and factors associated with inappropriate transfers. DESIGN: A structured implicit review (SIR) of medical records. SETTING AND PARTICIPANTS: Using nested random sampling in eight community SNFs, we identified SNF and hospital records of 100 unscheduled transfers to one of 10 hospitals. MEASUREMENTS: Seven trained physician reviewers assessed appropriateness using a SIR form designed for this study (2 independent reviews per record, 200 total reviews). We measured interrater reliability with kappa statistics and used bivariate analysis to identify factors associated with assessment that transfer was inappropriate. RESULTS: In 36% of ED transfers and 40% of hospital admissions, both reviewers agreed that transfer/admit was inappropriate, meaning the resident could have been cared for safely at a lower level of care. Agreement was high for both ED (percent agreement 84%, kappa .678) and hospital (percent agreement 89%, kappa .779). When advance directives were considered, both reviewers rated 44% of ED transfers and 45% of admissions inappropriate. Factors associated with inappropriateness included the perceptions that: (1) poor quality of care contributed to transfer need, (2) needed services would typically be available in outpatient settings, and (3) the chief complaint did not warrant hospitalization. CONCLUSIONS: Inappropriate transfers are a potentially large problem. Some inappropriate transfers may be associated with poor quality of care in SNFs. This study demonstrates that structured implicit review meets criteria for reliable assessment of inappropriate transfer rates. Structured implicit review may be a valuable tool for identifying inappropriate transfers from SNFs to EDs and hospitals.

Advance Directives↗
PubMed2000

The effect of moisture on compressional and shear wave speeds in unconsolidated granular material

The effect of water vapor on the shear and compressional wave speeds in two different kinds of glass beads and in Ottawa sand has been measured. The nominal diameter of the glass beads was 125 microm and of the sand, 500 microm. Measurements were made as the water vapor was introduced slowly into the evacuated material. The vapor pressure isotherm for the beads made of glass with a high concentration of titanium and barium oxides was fit reasonably well by the simple Brunauer-Emmett-Teller (BET) theory. For the Ottawa sand, the BET theory fit the vapor pressure isotherm if the surface area of the grains was assumed to be three times the area calculated, assuming all of the grains were spheres with a diameter of 500 microm. In these two materials, the vapor had little effect on the wave speeds. For beads made of glass containing sodium oxide, however, the wave speeds approximately double with the introduction of water vapor, and the vapor pressure isotherm had the BET shape only if the saturated vapor pressure was assumed to be lowered by 20%. These results have been explained by assuming that a chemical reaction occurred between the lime glass and the water to form a gel.

Journal Article↗
PubMed2000

The human histamine H(2) receptor regulates c-jun and c-fos in a differential manner.

Previously, we demonstrated that activation of the human H(2) receptor (hH(2)R) leads to an increase in c-fos transcription and cell proliferation. The purpose of these studies was to examine whether hH(2)R regulates c-jun expression and, if so, explore the mechanisms by which it does so. Histamine induced an increase in c-jun mRNA in human embryonic kidney cells stably transfected with the hH(2)R (maximal effect: 554.6 +/- 86.8% of control). The protein kinase C (PKC) inhibitors staurosporine (10(-6) M) and GF-109203X (10(-6) M) significantly inhibited histamine-stimulated c-fos mRNA while not altering c-jun expression. The protein kinase A (PKA) pathway inhibitors Rp-cAMP and protein kinase inhibitor did not affect the action of histamine on c-jun or c-fos mRNA. Histamine (10(-4) M) stimulated extracellularly regulated kinase 2 tyrosine phosphorylation. The specific inhibitor of the mitogen-activated protein (MAP) kinase pathway, PD-98059 (5 x 10(-5) M), significantly inhibited histamine-induced c-fos and c-jun mRNA. Of interest, the p70 S6 kinase inhibitor rapamycin (10(-6) M) but not wortmannin decreased histamine-stimulated c-jun mRNA by 58.5 +/- 12% (mean +/- SE, n = 4) while not significantly altering c-fos message. Histamine (10(-4) M) also led to an approximately 4.5-fold increase in Jun NH(2)-terminal kinase activity in a PKC-, PKA-, and MAP kinase-independent but rapamycin-sensitive manner. Our findings suggest that histamine stimulates both c-fos and c-jun mRNA in a differential manner. PKC is involved in histamine-mediated c-fos activation, whereas p70 S6 kinase is important for linkage of this receptor to c-jun.

Androstadienes↗
PubMed2000

Patterning of the C. elegans 1 degrees vulval lineage by RAS and Wnt pathways.

In C. elegans, the descendants of the 1 degrees vulval precursor cell (VPC) establish a fixed spatial pattern of two different cell fates: E-F-F-E. The two inner granddaughters attach to the somatic gonadal anchor cell (AC) and generate four vulF cells, while the two outer granddaughters produce four vulE progeny. zmp-1::GFP, a molecular marker that distinguishes these two fates, is expressed in vulE cells, but not vulF cells. We demonstrate that a short-range AC signal is required to ensure that the pattern of vulE and vulF fates is properly established. In addition, signaling between the inner and outer 1 degrees VPC descendants, as well as intrinsic polarity of the 1 degrees VPC daughters, is involved in the asymmetric divisions of the 1 degrees VPC daughters and the proper orientation of the outcome. Finally, we provide evidence that RAS signaling is used during this new AC signaling event, while the Wnt receptor LIN-17 appears to mediate signaling between the inner and outer 1 degrees VPC descendants.

Animals↗
PubMed2000

Nicotine-induced noradrenaline release from the isolated rat stomach by activation of L- and N-type calcium channels.

We examined the effect of nicotine on the release of endogenous noradrenaline (NA) from the isolated, vascularly perfused rat stomach. The stomach was perfused via the coeliac artery with Krebs-Ringer solution containing 10 microM pargyline at a constant flow rate of 4 ml per minute. Nicotine was once applied in the perfusion medium for 2 min. Nicotine (10(-6) - 10(-4) M) evoked NA release in a concentration-dependent manner. The nicotine (3 x 10(-5) M)-evoked NA release was abolished by hexamethonium and tetrodotoxin. Diltiazem and isradipine [blockers of L-type voltage-activated calcium channel (VACC)] and omega-conotoxin GVIA (a blocker of N-type VACC) also abolished this nicotine-evoked NA release. Previously we reported that N-type, but not L-type, VACCs are located on the gastric postganglionic sympathetic nerve terminals, since the NA release evoked by electrical stimulation of periarterial nerves around the left gastric artery (postganglionic sympathetic nerves) was abolished by omega-conotoxin GVIA, but not by diltiazem (Yokotani et al., Jpn. J. Pharmacol. 78, 75- 77, 1998). From these results, it was suggested that nicotine activates nicotinic acetylcholine receptors located on the sympathetic ganglia, thereby evoking NA release by activation of L-type VACC located on the gastric sympathetic ganglia and N-type VACC probably located on the sympathetic nerve terminals in the rat stomach.

Animals↗
PubMed2000

Coupling of human delta-opioid receptor to retinal rod transducin in Chinese hamster ovary cells.

Reverse transcription-polymerase chain reaction was used to identify the pertussis toxin (Ptx)-sensitive G protein alpha-subunit pool in Chinese hamster ovary (CHO) and mouse fibroblast (B82) cells. We detected the presence of mRNA for G(ialpha2), G(ialpha3), and G(oalpha) in both cell lines. G(ialpha1) and G(alphaz) mRNAs were not detected. We also found a homolog of the retinal rod transducin (G(talpha1)) in CHO, and the mouse cone transducin (G(talpha2)) in B82 cells. The presence of the transducin alpha-subunit proteins in CHO and B82 cells was confirmed by immunoprecipitation with specific antibodies. To test the interaction of heterologously expressed receptors with transducin in CHO cells, a Ptx-insensitive (C347S) rod transducin mutant was transfected into a CHO cell line stably expressing the human delta-opioid receptor (hDOR/CHO). (+)-4-[(alphaR)-alpha-((2S,2R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide, a selective delta-opioid receptor agonist, stimulated guanosine-5'-O-(3-[(35)S]thio)triphosphate binding by 293 +/- 36% after Ptx pretreatment in the mutant cell line with an EC(50) value of 54 +/- 32 nM, showing that transducin can functionally couple to the human delta-opioid receptors in these cells.

Animals↗
PubMed2000

A single cell analysis of Fas ligand positive T cells in rheumatoid synovial fluid.

OBJECTIVE: To investigate the function of Fas ligand (Fas-L) positive T cells in rheumatoid synovium, we analyzed the T cell receptor (TCR) CDR3 region and examined the expression of cytokines in both Fas-L+ and Fas-L- single T cells. METHODS: Synovial fluid (SF) samples were collected from 2 patients with rheumatoid arthritis. TCR BV8+ T cells were sorted into a 96 well plate at a density of one cell per well. Expression of Fas-L, interferon-gamma, interleukin 2 (IL-2), IL-4, IL-6, and IL-10 was analyzed by reverse transcription-polymerase chain reaction and Southern blot and the TCR BV8 junctional region was sequenced. RESULTS: Twenty-two of 30 TCR BV8+ T cells from Patient 1 and 20 of 43 TCR BV8+ T cells from Patient 2 were Fas-L+ T cells, while the others were Fas-L-. Junctional sequence analysis showed the presence of some conserved amino acid motifs in the CDR3 region (SRQ, GFG, SSG, SGS, LGTSGTL, TLSS) in 13 clones of Fas-L+ T cells from Patient 1, whereas no conserved amino acid motif in Fas-L-T cells was found. In Patient 2, conserved amino acid motifs (PGQ, GQG, TTWGA) in the CDR3 region were found in 6 clones of Fas-L+ T cells, while only one was found in 2 clones of Fas-L-cells. In Fas-L+ T cells, 90-93% expressed both IL-2 and IL-10 mRNA. CONCLUSION: Fas-L+ TCR BV8+ T cells revealed the conserved amino acids motif in the CDR3 region, suggesting that Fas-L+ T cells might expand by antigen stimulation and play a crucial role as Th0-type T cells in triggering autoimmunity in rheumatoid synovium.

Aged↗
PubMed2000

Are nonspecific practice guidelines potentially harmful? A randomized comparison of the effect of nonspecific versus specific guidelines on physician decision making.

OBJECTIVE: To test the ability of two different clinical practice guideline formats to influence physician ordering of electrodiagnostic tests in low back pain. DATA SOURCES/STUDY DESIGN: Randomized controlled trial of the effect of practice guidelines on self-reported physician test ordering behavior in response to a series of 12 clinical vignettes. Data came from a national random sample of 900 U.S. neurologists, physical medicine physicians, and general internists. INTERVENTION: Two different versions of a practice guideline for the use of electrodiagnostic tests (EDT) were developed by the U.S. Agency for Health Care Policy and Research Low Back Problems Panel. The two guidelines were similar in content but varied in the specificity of their recommendations. DATA COLLECTION: The proportion of clinical vignettes for which EDTs were ordered for appropriate and inappropriate clinical indications in each of three physician groups were randomly assigned to receive vignettes alone, vignettes plus the nonspecific version of the guideline, or vignettes plus the specific version of the guideline. PRINCIPAL FINDINGS: The response rate to the survey was 71 percent. The proportion of appropriate vignettes for which EDTs were ordered averaged 77 percent for the no guideline group, 71 percent for the nonspecific guideline group, and 79 percent for the specific guideline group (p = .002). The corresponding values for the number of EDTs ordered for inappropriate vignettes were 32 percent, 32 percent, and 26 percent, respectively (p = .08). Pairwise comparisons showed that physicians receiving the nonspecific guidelines ordered fewer EDTs for appropriate clinical vignettes than did physicians receiving no guidelines (p = .02). Furthermore, compared to physicians receiving nonspecific guidelines, physicians receiving specific guidelines ordered significantly more EDTs for appropriate vignettes (p = .0007) and significantly fewer EDTs for inappropriate vignettes (p = .04). CONCLUSIONS: The clarity and clinical applicability of a guideline may be important attributes that contribute to the effects of practice guidelines.

Decision Making↗
PubMed2000

Foot complications in people with diabetes: a community-based study in Taiwan.

BACKGROUND AND PURPOSE: This comparative cross-sectional and community-based study was aimed at defining foot complications in diabetic patients. These data have not yet been reported for Asian societies. METHODS: Of a population of 3,602 subjects aged 35 years or more in Chin-Shan, Taipei, 309 diabetic patients were identified. Two hundred and nineteen (71%) of those patients were compared to 100 individuals randomly selected for the nondiabetic control group in the same community. RESULTS: Three diabetic patients underwent lower extremity amputation and four had skin ulcerations. Diabetic patients had a significantly higher prevalence of peripheral neuropathy (32.4% vs 16%), arterial insufficiency (12.6% vs 3.0%), and medial arterial calcification (13.6% vs 5.0%), when compared to the nondiabetic controls. The age and sex-adjusted rates of hallux valgus, loss of skin hair on the dorsum of the foot, tinea unguium, arterial insufficiency, medial artery calcification, and peripheral neuropathy were significantly higher in diabetic than nondiabetic subjects. Aging and hyperglycemia (> 140 mg/dL) increased the prevalence of foot complications in both groups. Foot complications were also remarkably associated with the duration of diabetes (p = 0.003). CONCLUSIONS: This study shows that diabetes mellitus is associated with an increased likelihood of foot complications in this geographically defined Taiwanese population. Patient age and diabetic duration are associated with the significantly higher prevalence of foot complications.

Adult↗
PubMed2000

Anti-HBV effect of targeted antisense RNA against HBV C gene.

OBJECTIVE: To investigate the anti-HBV effect of targeted antisense RNA to hepatic cells. METHODS: pREP4-aC which would transcript antisense RNA against HBV C gene in eukaryotic cells were delivered into 2.2.15 cells by glactosylated poly-L-lisine (Gal-PLL), and the positive cells were selected. HBsAg, HBeAg and HBV DNA produced by 2. 2.15 cells were detected with ELISA or Southern blot during the experiment, and the cytotoxicity of targeted antisense on 2.2.15 cells was observed. RESULTS: The inhibition effect on HBsAg, HBeAg and HBV DNA occurred at the 24th hour after delivery and reached the highest level at the 6th day, and kept at lest two months. No cytotoxicity on 2.2.15 cells was observed. CONCLUSION: The targeted antisense against HBV C gene by delivery of Gal-PLL could effectively inhibit the antigen expression of HBV and DNA replication.

Antiviral Agents↗
PubMed2000

Inhibition of N-linked glycosylation down-regulates insulin-like growth factor-1 receptor at the cell surface and kills Ewing's sarcoma cells: therapeutic implications.

The insulin-like growth factor-1 receptor (IGF-1R) has been shown to be of critical importance for tumor development and tumor cell survival of various types of malignancies. We have previously demonstrated that an adequate N-linked glycosylation of IGF-1R is required for its translocation to the cell surface in melanoma cells. This raises the possibility of using glycosylation inhibitors as therapeutic agents against IGF-1R-dependent malignancies. In this study we show that inhibition of N-linked glycosylation using tunicamycin or the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor lovastatin resulted in down-regulation of IGF-1R at the cell surface in Ewing's sarcoma cell lines (RD-ES and ES-1 cells). The down-regulation of plasma membrane-bound IGF-1R was correlated with a drastic decrease in IGF-1R autophosphorylation, suggesting biochemical inactivation of the receptor. Whereas RD-ES and ES-1 cells responded differently with regard to DNA synthesis, the decrease in IGF-1R expression was accompanied by a rapid and substantial decrease in survival of both cell lines. Our data suggest that relatively untoxic HMG-CoA reductase inhibitors (e.g. lovastatin) could have therapeutic significance in IGF-1R-dependent neoplasms like Ewing's sarcoma.

Antineoplastic Agents↗