Biomedical subjects

T Wang

Publications and source records attributed to T Wang.

At least 559 records · Page 31Linked to original sources

PubMed1995

Circadian variation in human ventricular refractoriness.

BACKGROUND: The incidence of sudden cardiac death is highest in the morning hours. Although a circadian variation in myocardial ischemia may be responsible in part for this observation, other factors also may be contributory. It is not known whether a circadian variation in ventricular refractoriness exists that may be related to the increased morning incidence of sudden cardiac death. METHODS AND RESULTS: Nine subjects with primary conduction system disease, no evidence of structural heart disease, and permanent pacemakers were studied. Autonomic nervous system function as assessed by tilt table and baroreflex sensitivity testing was normal in all subjects. Using noninvasive programmed stimulation, ventricular effective refractory periods were measured hourly for 24 hours. Potassium, epinephrine, and norepinephrine levels also were measured hourly. In a subset of five subjects, ventricular refractory periods were again measured hourly over 24 hours during beta-blockade. A significant circadian variation in ventricular refractoriness was noted, with a mean difference between the shortest and longest refractory periods in individual subjects of 23 ms and 21 ms at drive cycle lengths of 600 ms and 400 ms, respectively. In eight subjects, the shortest refractory periods observed over 24 hours occurred within 2 hours of waking (random probability < 10(-8)). Adjustment of refractory period data according to the hour of waking resulted in a better correlation between ventricular refractory periods and time. Although a significant circadian variation was observed in potassium and catecholamine levels, neither was an independent predictor of refractory periods after adjustment for the hour of waking. The adjusted time of day was the only significant (P < .0001) independent predictor of refractory periods. beta-Blockade abolished the circadian variation in ventricular refractory periods. CONCLUSIONS: A significant circadian variation in ventricular refractory periods exists. Maximal shortening between hourly refractory periods as well as the shortest refractory periods occur in the early morning hours when the incidence of sudden cardiac death is greatest. Fluctuations in beta-adrenergic tone appear to be largely responsible for this phenomenon.

Adult↗

PubMed1995

Responses to chronic hypoxia in embryonic alligators.

To investigate developmental responses to chronic hypoxia, we incubated alligator eggs at 17% O2 and 21% O2 for the entire course of embryonic development and for 5 months post-hatching. Hypoxic-incubated alligators hatched later and at a smaller size. Hematocrit was significantly higher in hypoxic-incubated animals immediately post-hatch. Allosteric modification of hemoglobin oxygen affinity did not appear to play a role in the adaptation to hypoxia, given equal nucleotide triphosphate-to-hemoglobin ratios in the hypoxic and normoxic groups. When acutely exposed to 21% O2, hypoxic-incubated alligators maintained oxygen consumption relative to their normoxic siblings despite their lower mass.

Alligators and Crocodiles↗

PubMed1995

Molecular cloning and functional characterization of the Xenopus Ca(2+)-binding protein frequenin.

Frequenin was originally identified in Drosophila melanogaster as a Ca(2+)-binding protein facilitating transmitter release at the neuromuscular junction. We have cloned the Xenopus frequenin (Xfreq) by PCR using degenerate primers combined with low-stringency hybridization. The deduced protein has 70% identity with Drosophila frequenin and about 38-58% identity with other Ca(2+)-binding proteins. The most prominent features are the four EF-hands, Ca(2+)-binding motifs. Xfreq mRNA is abundant in the brain and virtually nondetectable from adult muscle. Western blot analysis indicated that Xfreq is highly concentrated in the adult brain and is absent from nonneural tissues such as heart and kidney. During development, the expression of the protein correlated well with the maturation of neuromuscular synapses. To determine the function of Xfreq at the developing neuromuscular junction, the recombinant protein was introduced into Xenopus embryonic spinal neurons by early blastomere injection. Synapses made by spinal neurons containing exogenous Xfreq exhibited a much higher synaptic efficacy. These results provide direct evidence that frequenin enhances transmitter release at the vertebrate neuromuscular synapse and suggest its potential role in synaptic development and plasticity.

Amino Acid Sequence↗

PubMed1995

Activation of ZAP-70 kinase activity by phosphorylation of tyrosine 493 is required for lymphocyte antigen receptor function.

ZAP-70 is a protein tyrosine kinase (PTK) required for T-cell development and T-cell antigen receptor (TCR) function. ZAP-70 is associated with the phosphorylated antigen receptor and undergoes tyrosine phosphorylation following receptor activation. We demonstrate here that tyrosine phosphorylation of ZAP-70 results in an increase in its catalytic activity and that this activation is mediated by the phosphorylation of tyrosine residue 493 by the src family of PTKs. The activity of baculoviral expressed ZAP-70 was up-regulated 10-fold when ZAP-70 was co-infected and phosphorylated by the src family PTK, lck. Mutation of Y493 alone abrogated the ability of ZAP-70 to be activated by lck. Moreover, we demonstrate that phosphorylation of Y493 and activation of ZAP-70 is required for antigen receptor-mediated induction of interleukin-2 (IL-2) secretion in lymphocytes.

Amino Acid Sequence↗

PubMed1995

Cerebellar interpositus nucleus modulates neuronal activity of lateral hypothalamic area.

Effects of stimulating the cerebellar interpositus nucleus (IN) on the neuronal activity of lateral hypothalamic area (LHA) were first observed in the cat. The results showed that (1) IN stimulation could elicit inhibitory, excitatory, inhibitory-excitatory and excitatory-inhibitory responses from LHA neurones, with a majority of inhibitory responses (46.9%); (2) the responsive latencies of LHA neurones to IN stimulation ranged from 5 to 45 ms, while most (83.6%) showed a short latency of < 15 ms; (3) of 67 LHA neurones which responded to the IN stimulation, 42 (62.7%) cells were identified to be glucose-sensitive neurones. These results suggest that IN may be involved in the role of LHA modulating food intake behaviour, as well as other non-somatic functions.

Animals↗

PubMed1995

Nitric oxide mediates activity-dependent synaptic suppression at developing neuromuscular synapses.

Temporal correlation between pre- and postsynaptic activities is an important mechanism that regulates synaptic connectivity during development and synaptic plasticity in the adult. In developing neuromuscular junctions, postsynaptic activity is critical in functional suppression and, ultimately, elimination of the synapses. Although repetitive postsynaptic firing asynchronous to the presynaptic activity results in a persistent synaptic suppression, the underlying molecular mechanism remains unknown. Here we provide evidence that nitric oxide (NO), a free radical implicated in several forms of synaptic plasticity, may serve as a retrograde signal for activity-dependent suppression in the neuromuscular synapse. NO donors and activators of the cyclic GMP pathway suppressed spontaneous and evoked synaptic currents. Moreover, the synaptic suppression induced by repetitive postsynaptic depolarization was prevented by the NO-binding protein haemoglobin and by inhibitors of NO synthase. Thus, synaptic suppression may be triggered by NO released from a postsynaptic myocyte that fires asynchronously to the presynaptic terminal.

Action Potentials↗

PubMed1995

Evaluation of free PSA isoforms, PSA complex formation, and specificity of anti-PSA antibodies by HPLC and PAGE-immunoblotting techniques.

Both high performance liquid chromatographic (HPLC) and polyacrylamide gel electrophoresis-immunoblotting (PAGE-immunoblotting) procedures have been established for the study of isoforms of free prostate-specific antigen (PSA) and the complex formation between free PSA and protease inhibitors, and for the evaluation of the specificities of various anti-PSA antibodies. We found multiple isoforms of free PSA on PAGE, which were all capable of forming complexes with protease inhibitors. The same isoform pattern can be produced from the original seminal fluid. The PSA isoforms differ from each other most likely in charge because they could be converted to one band on SDS-PAGE and to a single peak by gel filtration chromatography. We found it difficult to form large quantities of PSA complex when mixing free PSA from seminal fluid with protease inhibitors, regardless of whether the free PSA or the protease inhibitors were in excess. Except for the PSA-ACT complex, which was consistently detectable by both HPLC and PAGE-immunoblotting techniques after incubation, these two procedures disagreed in their detection of PSA-A2M and PSA-AT complexes. The PSA-A2M complex was usually observable by immunoblotting techniques but barely detectable on HPLC, whereas PSA-AT was totally invisible by immunoblotting but appeared as a peak in the HPLC elution profile. Mixing free PSA with serum clearly resulted in both PSA-ACT and PSA-A2M complexes. However, more PSA-ACT than PSA-A2M was formed; the result was also confirmed by using 125I-PSA for mixing. PSA could be separated into active and inactive PSA by DEAE Sepharose chromatography with a 14-fold difference in protease activity. The difference in enzymatic activity apparently had no effect on complex formation. All the anti-PSA antibodies examined in this study reacted with PSA isoforms, PSA-ACT and PSA-A2M complexes. We conclude that it would be almost impossible to establish an assay to measure all forms of PSA in the serum and to expect to produce precise and accurate PSA values.

Antibody Specificity↗

PubMed1995

Interference in triiodothyronine (T3) analysis on the Immuno 1 Analyzer.

OBJECTIVE: To evaluate the interference in Triiodothyronine (T3) analysis on the Immuno 1 Analyzer. METHODS: We analyzed 686 samples for T3 using the Miles Technicon Immuno 1 Analyzer. We compared the results of 318 samples with those given by radioimmunoassay (RIA) and the remaining 368 results with those given by the Ciba-Corning ACS 180 analyzer. RESULTS: On the Immuno 1 correlated with those by RIA or chemiluminescence immunoassay. However, results on eight patients by the Immuno 1 method were anomalously elevated. We attempted to find and eliminate the cause of the interference on the Immuno 1. Although the method uses an alkaline phosphatase labelled T3 analog and fluoresceinated monoclonal antibody, serum binding of fluorescein or alkaline phosphatase did not appear to be the major causes of the interference. Ethanol extraction of samples followed by reconstitution in zero calibrator was the only reliable way to eliminate the interference. CONCLUSION: The Immuno 1 assay was more prone to interference than other methods. Until it is reformulated, we recommend that users assay ethanol extracts of samples with unexpectedly high T3.

Alkaline Phosphatase↗

PubMed1995

Breathing pattern and cost of ventilation in the American alligator.

The energetic cost of pulmonary ventilation is termed the "cost of breathing" and is commonly determined from the change in oxygen uptake with altered ventilation. Previous analyses of lung mechanics predicts increased tidal volume would be more expensive than increased breathing frequency. Existing studies on the oxidative cost of breathing have, however, not addressed breathing pattern. We stimulated ventilation in juvenile alligators by either hypoxia or hypercapnia. Both hypoxia and hypercapnia increased ventilation (ten- and six-fold, respectively), but through entirely different changes in frequency and tidal volume combination. Hypoxia increased frequency from 1.4 to 6.0 breaths min -1 and tidal volume from 11.3 to 25.9 ml kg -1. During hypercapnia frequency remained constant, while tidal volume increased from 8.7 to 63.2 ml kg -1. Oxygen uptake remained constant at approximately 0.65 ml O2 kg -1 min -1 during all hypercapnic exposures, whereas oxygen uptake doubled during severe hypoxia. Extrapolating oxygen uptake to zero ventilation provides an estimate of non-ventilatory metabolic rate. Thus, ventilatory contributions to overall metabolic rate can be calculated. The cost of breathing estimated by hypoxic exposures (15% of total metabolic rate at rest) is markedly higher than that provided by hypercapnia (1-5% of total metabolic rate at rest). These data are in contrast to the predictions based on pulmonary mechanics.

Alligators and Crocodiles↗

PubMed1995

NMDA, kainate, and AMPA depolarize nondopamine neurons in the rat ventral tegmentum.

The possible existence of N-methyl-D-aspartate (NMDA) and non-NMDA receptors on electrophysiologically identified nondopamine neurones in the ventral tegmental area (VTA) was tested in rat midbrain slice preparations. NMDA, kainate (KA), and AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) depolarized the membrane potential of nondopamine neurons in a dose-dependent manner. The NMDA effect was blocked by the selective NMDA receptor antagonist, CGS 19755 (cis-4-phosphonomethyl-2-piperidine carboxylate), but not by the non-NMDA receptor antagonist, NBQX [2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline]. In contrast, the effects of KA and AMPA were antagonized by NBQX, but not by CGS 19755. The rank order potency of the three agonists was AMPA > KA > NMDA, with thresholds of 0.1, 0.3, and 3 microM, respectively. These results provide clear electrophysiological evidence that nondopamine neurons in the ventral tegmental area possess both NMDA and non-NMDA receptors.

Animals↗

PubMed1995

Effects of chronic hyperfiltration on proximal tubule bicarbonate transport and cell electrolytes.

The compensatory response to unilateral nephrectomy (UNX) was investigated by a combination of renal clearance, microperfusion, electron microprobe, and morphological techniques. Filtration rate was significantly elevated 21 days following UNX and associated with a marked stimulation of bicarbonate and fluid absorption in the proximal tubule. Analysis of kinetic data of bicarbonate transport demonstrated strong flow-dependent activation of bicarbonate absorption in both control and experimental condition. The bicarbonate level at which half-saturation (apparent Kd) of transport occurred decreased uniformly at higher flow rates, but maximal transport rates (apparent Vmax) in the proximal tubule doubled in the remnant kidney. The flow dependence of bicarbonate transport in control and experimental conditions can be explained by an apparent unstirred layer effect modifying radial bicarbonate gradients in the tubule. Both Na/H-exchange and electrogenic H secretion contribute to bicarbonate absorption, but only Na/H-exchange increased significantly in proximal tubules of UNX rats. Cell ion concentrations after UNX were unchanged in cortical tubules, consistent with proportionately enhanced apical and basolateral ion transport. Proximal tubule cell rubidium concentration measured after a 30-second rubidium infusion as an index of basolateral Na,K-ATPase activity was unchanged in UNX rats. Inasmuch as cell volume increased significantly (25%), these data are consistent with a proportionate and similar stimulation of rubidium uptake and Na,K-ATPase activity.

Animals↗

PubMed1995

Mice lacking ornithine-delta-aminotransferase have paradoxical neonatal hypoornithinaemia and retinal degeneration.

Deficiency of ornithine-delta-aminotransferase (OAT) in humans causes hyperornithinaemia and gyrate atrophy (GA), a blinding chorioretinal degeneration. Surprisingly, OAT-deficient mice produced by gene targeting exhibit neonatal hypoornithinaemia and lethality, rescuable by short-term arginine supplementation. Post-weaning, these mice develop hyperornithinaemia similar to human GA patients. Subsequent studies in one human GA infant also showed transient hypoornithinaemia. Thus, the OAT reaction plays opposite roles in neonatal and adult mammals. Over several months, OAT-deficient mice develop a retinal degeneration with involvement of photoreceptors and pigment epithelium. OAT-deficient mice appear to be an excellent model of human GA.

Adult↗

PubMed1995

Differences in transcription and translation of long and short Gs alpha, the stimulatory G-protein, in human atrium.

1. We have previously reported the relative mRNA and protein level of the long and short splice variants of Gs alpha (Gs alpha L and Gs alpha S) in human atrium. We have now measured the relative proportions of the serine+ and serine- variants of Gs alpha L and Gs alpha S in human atrium, and assessed, indirectly, whether their differential expression may (i) regulate Gs alpha phosphorylation, and (ii) be regulated by atrial cyclic AMP levels. 2. The serine+ and serine- variants of Gs alpha L and Gs alpha S were estimated by single nucleotide primer extension in 36 right atrial strips of which half were from beta-adrenoceptor-blocked patients. The ratio of serine+ to serine- variants was 0.06 +/- 0.12 for Gs alpha L, compared with 8.04 +/- 12.16 for Gs alpha S (P < 0.001). 3. Isoelectric points of Gs alpha and Gs alpha S in the atria of four beta-adrenoceptor-blocked and four non-beta-adrenoceptor-blocked patients were estimated by two-dimensional gel electrophoresis. Two-dimensional gel analysis gave a consistent pattern with several spots for both Gs alpha L and Gs alpha S; however, the isoelectric points of Gs alpha S were more acid (5.18 +/- 0.24) than those of Gs alpha L (5.87 +/- 0.17, P < 0.001). 4. No significant difference in either the serine variants or isoelectric point value was observed between beta-adrenoceptor-blocked and non-beta-adrenoceptor-blocked patients. 5. In conclusion, all four Gs alpha variants were expressed in human atrium, but Gs alpha L is almost entirely of the serine- form. Gs alpha S has a more acidic isoelectric point than Gs alpha L, indicating a possible post-translational modification. The lack of difference in our results between beta-adrenoceptor-blocked and non-beta-adrenoceptor-blocked patients suggests indirectly that cyclic AMP is an unlikely candidate for regulating splicing or post-translational modification of Gs alpha in vivo.

Adrenergic beta-Antagonists↗

PubMed1995

The rho-GAP encoded by BEM2 regulates cytoskeletal structure in budding yeast.

Microfilaments are required for polarized growth and morphogenesis in Saccharomyces cerevisiae. To accomplish this, actin cables and patches are redistributed during the cell cycle to direct secretory components to appropriate sites for cell growth. A major component of actin cables is tropomyosin I, encoded by TPM1, that determines or stabilizes these structures. Disruption of TPM1 is not lethal but results in the loss of actin cables and confers a partial defect in polarized secretion. Using a synthetic lethal screen, we have identified seven mutations residing in six genes whose products are required in the absence of Tpm1p. Each mutant exhibited a morphological defect, suggesting a functional link to the actin cytoskeleton. Complementation cloning of one mutation revealed that it lies in BEM2, which encodes a GTPase-activating protein for the RHO1 product. bem2 mutations also show synthetic lethality with rho1 and mutations in certain other cytoskeletal genes (ACT1, MYO1, MYO2, and SAC6) but not with mutations in several noncytoskeletal genes. These data therefore provide a genetic link between the GAP encoded by BEM2 and the functional organization of microfilaments. In addition, we show that bem2 mutations confer benomyl sensitivity and have abnormal microtubule arrays, suggesting that the BEM2 product may also be involved directly or indirectly in regulating microtubule function.

Actin Cytoskeleton↗

PubMed1995

Effect of variations in oral fat and carbohydrate load on postprandial lipemia.

In this study we assessed the acute effects of the consumption of varying amounts of fat and fructose on the magnitude of postprandial lipemia. Subjects were studied after an overnight fast on four separate mornings, ingesting in random order 5, 40, or 80 g fat, or 5 g fat plus 50 g fructose. Vitamin A (36 mg, or 120,000 U retinol) was also given and blood was drawn at frequent intervals over the next 10 h for measurement of triacylglycerol and retinyl palmitate (RP) concentrations in plasma and the Sf > 400 and Sf 20-400 lipoprotein fractions. (Sf denotes flotation units.) In general, the postprandial triacylglycerol response increased in plasma and in both lipoprotein fractions as a function of both the baseline fasting triacylglycerol concentration and the amount of fat ingested. However, no matter how high the fasting plasma triacylglycerol concentration, there was no increase in the postprandial triacylglycerol concentration in plasma or either lipoprotein fraction after the 5-g oral fat load. The results of the measurements of RP concentration were somewhat similar in that there was a dose-dependent increase in the plasma and the Sf > 400 lipoprotein fraction in response to the higher fat loads. However, just the opposite was true in the Sf 20-400 lipoprotein fraction, for which the increase in RP concentration was inversely related to the size of the fat load.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Multilocus analysis for gene-centromere mapping using first polar bodies and secondary oocytes.

Polar body and oocyte typing is a new technique for gene-centromere mapping and for generating female linkage maps. A maximum likelihood approach is presented for ordering multiple markers relative to the centromere and for estimating recombination frequencies between markers and between the centromere and marker loci. Three marker-centromere orders are possible for each pair of markers: two orders when the centromere flanks the two markers and one order when the centromere is flanked by the two markers. For each possible order, the likelihood was expressed as a function of recombination frequencies for two adjacent intervals. LOD score for recombination frequency between markers or between the centromere and a marker locus was derived based on the likelihood for each gene-centromere order. The methods developed herein provide a general solution to the problem of multilocus gene-centromere mapping that involves all theoretical crossover possibilities, including four-strand double crossovers.

Animals↗

PubMed1995

Photosynthesis and canopy characteristics in genetically defined families of silver birch (Betula pendula).

Net photosynthetic rates (A) of leaves in upper and lower crown layers (A(upper) and A(lower)), leaf area index (LAI), mean tilt angle (MTA), several leaf characteristics, and volume growth were observed in fast- and slow-growing families of a 14-year-old full-sib and half-sib family progeny test of Betula pendula Roth. Each measure of net photosynthetic rate was calculated after correcting measured net photosynthesis for the effects of environmental variables. The differences in A(upper) and LAI among families were significant. The proportions of the total variance assigned to family for A(upper), A(lower) and LAI were 33.64, 28.93 and 54.99%, respectively. The mean A(upper) and LAI of the fast-growing families were significantly higher than those of the slow-growing families, whereas the mean A(lower) of the fast-growing families was significantly lower than that of the slow-growing families. There were also significant differences among families in leaf size, leaf shape, and the ratios leaf fresh weight/area and leaf dry weight/area. Between 27.55 and 54.55% of the total variance in these characteristics could be assigned to the family effect. Volume growth was positively correlated with A(upper) and LAI, but it was most strongly correlated with A(upper) x LAI.

Journal Article↗

PubMed1995

Survival mechanisms of vertebrate ectotherms at subfreezing temperatures: applications in cryomedicine.

Various marine fishes, amphibians, and reptiles survive at temperatures several degrees below the freezing point of their body fluids by virtue of adaptive mechanisms that promote freeze avoidance or freeze tolerance. Freezing is avoided by a colligative depression of the blood freezing point, supercooling of the body fluids, or the biosynthesis of unique antifreeze proteins that inhibit the propagation of ice within body fluids. Conversely, freeze tolerance is an adaptation for the survival of tissue freezing under ecologically relevant thermal and temporal conditions that is conferred by the biosynthesis of permeating carbohydrate cryoprotectants and an extensive dehydration of tissues and organs. Such cryoprotective responses, invoked by the onset of freezing, mitigate the osmotic stress associated with freeze-concentration of cytoplasm, attendant metabolic perturbations, and physical damage. Cryomedical research has historically relied on mammalian models for experimentation even though endotherms do not naturally experience subfreezing temperatures. Some vertebrate ectotherms have "solved" not only the problem of freezing individual tissues and organs, but also that of simultaneously freezing all organ systems. An emerging paradigm in cryomedicine is the application of principles governing natural cold hardiness to the development of protocols for the cryopreservation of mammalian tissues and organs.

Adaptation, Physiological↗