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Biomedical subjects

L Wang

Publications and source records attributed to L Wang.

At least 1,243 records · Page 69Linked to original sources
PubMed1998

Protein tyrosine kinase is downstream of protein kinase C for ischemic preconditioning's anti-infarct effect in the rabbit heart.

The present study tested the hypothesis that one or more tyrosine kinase(s) are downstream of protein kinase C (PKC) in the signal transduction pathway responsible for the cardioprotective effect of ischemic preconditioning (PC). Isolated rabbit hearts were subjected to 30 min of regional ischemia followed by 2 h of reperfusion. Infarct size was measured by triphenyltetrazolium staining and expressed as a percentage of the area at risk. Infarction in control hearts was 32.9+/-1.8%. Ischemic PC with 5-min ischemia/10-min reperfusion reduced infarct size to 11.5+/-1.5% (P<0.05). Infusion of the tyrosine kinase inhibitors, genistein (50 microM) or lavendustin A (0.5 microM), alone did not affect the level of infarction. When infused around the 5-min PC ischemia genistein failed to block protection (13.7+/-1.0%). However, when present at the onset of the 30-min ischemia both genistein and lavendustin A completely aborted protection (31.4+/-2.0 and 28.1+/-1.5%, respectively). Activation of PKC by phorbol 12-myristate 13-acetate (PMA, 0.05 nmol) was as protective is ischemic PC (14.9+/-3.0%; P<0. 05). Similar to PC, PMA-induced protection was completely prevented by both genistein and lavendustin A. Conversely, anisomycin (50 ng/ml), an activator of MAP kinase kinases (dual tyrosine and threonine kinases), was very protective (7.5+/-1.6%; P<0.05) and this protection was still present when PKC was inhibited by 5 microM chelerythrine (12.1+/-1.6%; P<0.05). In conclusion, activation of a tyrosine kinase during the long ischemia appears to be required for cardioprotection in the rabbit heart. Furthermore, the ability of tyrosine kinase inhibitors to block PMA-induced protection in conjunction with the failure of PKC inhibition to prevent anisomycin-induced protection suggests that the tyrosine kinase is downstream of PKC and that the tyrosine kinase may be a MAP kinase kinase.

Alkaloids↗
PubMed1998

A high affinity binding site for [3H]-Dofetilide on human leukocytes.

Certain Class III anti-arrhythmic agents have been shown to interact with human leukocytes and after antigenic and mitogenic activation. We hypothesized that a binding site for the Class III anti-arrhythmic agent, dofetilide, would exist on human leukocytes. Analysis of binding isotherms defined the presence of a single high affinity binding site on mononuclear cells and neutrophils: Kd 26+/-4 nm, Bmax 61+/-14 fmol/10( 6) cells and Kd 33+/-14 nm, Bmax 163+/-45 fmol/10(6) cells, respectively. Other Class III drugs inhibited [3H]-dofetilide binding at physiologically relevant concentrations, but the IC50 values of E4031 and quinidine were significantly higher for leukocytes than for cardiac myocytes. Interestingly, verapamil inhibited [3H]-dofetilide binding to leukocytes, but not to cardiac myocytes at physiologic concentrations (10 microM). Charybdotoxin and tetraethlyammonium inhibited [3H]-dofetilide binding to leukocytes at microM mm concentrations, respectively, however, apamin did not inhibit binding even at 1 microM concentrations. These data suggest that a Ca2+-activated K+ channel, like K(Ca) mini (apamin-insensitive isoform), is a candidate for the leukocyte [3H]-dofetilide binding site. To assess the functional significance of defetilide binding to leukocyte biology, we evaluated fMLP-stimulated superoxide production in the presence or absence of dofetilide. Dofetilide, at 30 nm suppressed of superoxide production. In conclusion, dofetilide binds to human leukocytes at physiologic concentrations and this binding alters leukocyte function possibly through interaction with a Ca2+-activated K+ channel.

Animals↗
PubMed1998

Changes of gastric nitric oxide in neonatal rats with hypoxic-ischemic encephalopathy.

In order to study the changes of nitric oxide (NO) in gastric wall in hypoxic neonatal rats, the activity of nitric oxide synthase (NOS) of gastric wall was measured and the NADPH-diaphorase biochemistry test was taken to show the distribution of NOS in the gastric wall of neonatal rats. The results showed that compared with normal rats, NOS had no significant changes in the acute hypoxic rats (P > 0.05). However, in hypoxic-ischemic encephalopathy (HIE) neonatal rats, the activity of NOS was markedly increased (P < 0.01), and the NOS positive reactive products were markedly increased in the gastric muscle, but no changes in the mucosal and submucosal layers were observed. The results suggest that the decreased gastric motivation and the gastric mucosal lesions caused by asphyxia are associated with the changes of NO in gastric wall.

Animals↗
PubMed1998

Clinical study on chronopharmacokinetics of digoxin in patients with congestive heart failure.

Fluorescence polarization immunoassay was used to study the chronopharmacokinetics of digoxin in 10 patients with congestive heart failure (CHF) who also served as self-controls. Our results showed that the serum digoxin concentration reached peak value 1 h after taking digoxin at 7:00 a.m., but the serum digoxin concentration reached the peak value 2 h after taking digoxin at 4:00 p.m. The average serum digoxin concentration area under curve was greater and the best maintainable time of serum concentration within 24 h after taking digoxin at 4 p.m. longer than those at 7:00 a.m. The heart rates were obviously lower and the cardiac function was significantly improved in 4:00 p.m. group.

Adult↗
PubMed1998

A possible basic cortical microcircuit called "cascaded inhibition." Results from cortical network models and recording experiments from striate simple cells.

The robust behavior, the degree of response linearity, and the aspect of contrast gain control in visual cortical simple cells are (amongst others) the result of the interplay between excitatory and inhibitory afferent and intracortical connections. The goal of this study was to suggest a simple intracortical connection pattern, which could also play a role in other cortical substructures, in order to generically obtain these desired effects within large physiological parameter ranges. To this end we explored the degree of linearity of spatial summation in visual simple cells experimentally and in different models based on half-wave rectifying cells ("push-pull models"). Visual cortical push-pull connection schemes originated from antagonistic motor-control models. Thus, this model class is widely applicable but normally requires a rather specific design. On the other hand we showed that a more generic version of a push-pull model, the so-called cascaded inhibitory intracortical connection scheme, which we implemented in a biologically realistic simulation, naturally explains much of the experimental data. We investigated the influence of the afferent and intracortical connection structure on the measured linearity of spatial summation in simple cells. The analysis made use of the relative modulation measure, which is easy to apply but is limited to moving sinusoidal grating stimuli. We introduced two basic push-pull models, where the order of threshold nonlinearity and linear summation is reversed. Very little difference is observed with the relative modulation measure for these models. Alterative models, like half-wave squaring models, were also briefly discussed. Of all model parameters, the ratio of excitation to inhibition in the simple cell exerts the most crucial influence on the relative modulation. Linearity deteriorates as soon as excitatory and inhibitory inputs are imbalanced and the relative modulation drops. This prediction was tested experimentally by extracellular recordings from cat area 17 simple cells and we found that about 62% showed a significant deviation from linear behavior. The problem that individual basic push-pull models are hard to distinguish experimentally led us to suggest a different solution. In order to generically account for the observed behavior (e.g., imbalance of excitation versus inhibition), we suggested a rather generic version of a push-pull model where it no longer mattered about (the hard-to-distinguish) fine differences in connectivity. Thus, we introduced a new class of biophysically realistic models ("cascaded inhibition"). This model class requires very little connection specificity and is therefore highly robust against parameter variations. Up to 25 cells are connected to each target cell. Thereby a highly interconnected network is generated, which also leads to disinhibition at some parts of an individual receptive field. We showed that the performance of these models simulates the degree of linearity and its variability in recal simple cells with comparatively high accuracy. This behavior can be explained by the self-regulating properties of a cascaded inhibitory connection scheme by which the balance between excitation and inhibition at a given cell is improved by the joint network effects. The virtues and the generic design of this connection pattern, therefore, allow to speculate that it is used also in other parts of the cortex.

Animals↗
PubMed1998

Photolysis of phloxine B in water and aqueous solutions

Phloxine B (2',4',5',7'-tetrabromo-4,5,6,7-tetrachlorofluorescein disodium salt) as a potential photoactive insecticide was rapidly photodegraded in water under various light sources. Two major photolytic products characterized were 2',4',5'-tribromo-4,5,6, 7-tetrachlorofluorescein and 4',5'-dibromo-4,5,6, 7-tetrachlorofluorescein. The photolysis rates of phloxine B were influenced by various factors including salts in medium, sample pH, and light sources. Half-lives (t(1/2)) of phloxine B spiked in different water samples and 2% NaCl solution at 29 +/- 1 degreesC ranged from 0.70 to 1.28, 26.3 to 115, and 14.1 to 46.2 hours under 254 nm, 365 nm, and cool white fluorescent lights, respectively. Half-lives of phloxine B in tap, stream, or seawater in a beaker were from 10 to 13 min under sunlight at ambient air temperature. In a range of buffer pH 6-8 at 29 +/- 1 degreesC, phloxine B photodegraded slightly faster in acidic solution than in basic solution. The photolysis t(1/2) of phloxine B at 29 +/- 1 degreesC was 25, 32, 128, and 755 min in the buffered NaF, NaCl, NaBr, and NaI solutions, respectively. The t(1/2) of phloxine B was 31 min when phloxine B was dissolved in the sodium phosphate buffer as control. Sodium iodide and ammonium iodide photostabilized phloxine B 24 and 27 folds, respectively, when it was compared with the buffer control.

Journal Article↗
PubMed1998

Evaluation of the effectiveness of preoperative embolization in surgery for nasopharyngeal angiofibroma.

We retrospectively analyzed the clinical data of 21 patients (22 procedures) with histologically proven nasopharyngeal angiofibromas. Eleven patients underwent preoperative intra-arterial digital subtraction angiography (IADSA) and embolization with Gelfoam. Embolization reduced the intraoperative blood loss from an average of 1136 ml in the non-embolized patients to 677 ml in the embolized cases (P < 0.05) and transfusions from an average of 836 ml to 400 ml (P < 0.01). Results again show that preoperative embolization is effective in reducing intraoperative blood loss.

Adolescent↗
PubMed1998

Modulation of cloned human neuronal voltage-gated potassium channels (hKv1.1 and hKv2.1) by neurosteroids.

Two voltage-gated potassium channels, hKv1.1 and hKv2.1, were stably expressed in Chinese hamster ovary cells. The effects of neurosteroids, pregnenolone sulfate (PS), 5alpha-pregnan-3alpha-ol-20-one sulfate (5alpha3alphaP), and 5beta-pregnan-3alpha-ol-20-one sulfate (5beta3alphaP), on hKv1.1 and hKv2.1 were studied using the patch-clamp method. PS, 5alpha3alphaP, and 5beta3alphaP shifted current/voltage (I/V) relationship of both channels to the left by about 10 mV. The neurosteroids also increased the current amplitude voltage dependently. The activation time constants (taua) for hKv1.1 and hKv2.1 were voltage dependent and decreased with membrane depolarization. At -20 mV, PS reduced taua for hKv1.1 by 8 ms and 15 ms at 10 and 100 microM respectively. PS also significantly decreased the taua of hKv2.1 by 30 ms (10 microM) and 38 ms (100 microM) at +10 mV. However, only at 100 microM did 5alpha3alphaP or 5beta3alphaP significantly alter the taua of hKv1.1. Neither 5alpha3alphaP nor 5beta3alphaP affected the taua of hKv2.1. Deactivation time constants (taud) were also voltage dependent and, in contrast to taua, taud was prolonged with membrane depolarization. At 100 microM, PS, 5alpha3alphaP, and 5beta3alphaP significantly increased the taud for hKv1.1 but did not affect the taud for hKv2.1.

Animals↗
PubMed1998

Immunohistochemical detection of polycyclic aromatic hydrocarbon-DNA damage in human blood vessels of smokers and non-smokers.

The presence of cigarette smoking-related polycyclic aromatic hydrocarbon (PAH)-DNA adducts was investigated in human arterial tissue using an immunoperoxidase staining method with a monoclonal antibody that recognizes benzo(a)pyrene and structurally related PAH diol epoxide-DNA adducts. This is the first time that immunohistochemical methods for detection of PAH-DNA damage have been applied to human endothelial and smooth muscle cells of blood vessels. Internal mammary artery specimens from a total of 37 smokers and non-smokers were tested. Positive nuclear staining was observed in both endothelial and smooth muscle cells, with higher staining in the endothelium. The correlation between smoking status, available for 33 subjects, and detectable PAH-DNA adducts in endothelium did not reach statistical significance (odds ratio = 3.38, 95% confidence interval is 0.47-27.60) in this small series. While no causal role can be inferred from our results, they support the theory that endothelial injury caused by cigarette smoking and other environmental exposures may be an early event in the process of atherosclerosis.

Adult↗
PubMed1998

Determination and estimation of water solubilities and octanol/water partition coefficients for derivates of benzanilides.

A shake-flask method was used to determine the water solubilities (Sw) and the octanol/water partition coefficients(Kow) of 14 derivates of benzanilides. The results showed that the octanol/water partition coefficients were correlated (r=-0.93) with Sw. The linear solvation energy relationship(LSER) and molecular connectivity methods have been used to establish correlation equation successfully. The LSER method was used to predict these partitioning properties more accurately. The estimated values were well fitted with observed ones.

Benzamides↗
PubMed1998

Detection of GB virus C by the RT-PCR LCx system.

The recent publication of representative genomic sequences of GBV-C has permitted the selection of PCR primers for detection of GBV-C in clinical samples by PCR techniques. Traditional amplification methodologies which couple reverse transcription polymerase chain reaction (RT-PCR) and Southern blot detection are slow, cumbersome, and can be technique dependent. This has hampered studies to determine the clinical significance of GBV-C. We report the selection of highly conserved PCR primers and a probe useful for semi-automated RT-PCR using the Abbott LCx system. This adaptation of the LCx system expands its capabilities to include the detection of RNA by RT-PCR, in addition to DNA detection by ligase chain reaction (LCR).

Automation↗
PubMed1998

Enzymatic degradation of luteinizing hormone releasing hormone (LHRH)/[D-Ala6]-LHRH in lung pneumocytes.

PURPOSE: To investigate the cellular proteolytic activities of various lung pneumocytes using luteinizing hormone releasing hormone (LHRH) and [D-Ala6]-LHRH as model peptide substrates. METHODS: HPLC analysis was used to investigate the degradation kinetics of LHRH/[D-Ala6]-LHRH and to identify their degradation products in isolated lung pneumocytes. RESULTS: Pulmonary macrophages exhibited the strongest proteolytic activity against LHRH)/[D-Ala6]-LHRH, followed by type II and type I-like pneumocytes. Three major degradation products of LHRH, namely LHRH 4-10, LHRH 6-10, and LHRH 7-10, were identified in macrophages and type II pneumocytes, whereas in type I-like pneumocytes only the LHRH 7-10 was found. Co-incubation of the cells with known enzyme inhibitors including captopril (an ACE inhibitor), thiorphan (an EP24.11 inhibitor), and EDTA (an EP24.15 inhibitor) inhibited the formation of LHRH 4-10, LHRH 7-10, and LHRH 6-10 respectively. In all cell types, the degradation rate of [D-Ala6]-LHRH was about 3-8 times lower than that of LHRH. This peptide analog was resistant to degradation by EP24.15 and EP24.11, but was susceptible to ACE. CONCLUSIONS: ACE, EP24.11, and EP24.15 are the major enzymes responsible for the degradation of LHRH in macrophages and type II pneumocytes. The magnitude of peptidase activities in these cell types are: EP24.15 > EP24.11 approximately ACE. No EP24.15 or ACE activity was observed in type I-like pneumocytes and only a weak EP24.11 activity was detected.

Animals↗