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Biomedical subjects

W Wang

Publications and source records attributed to W Wang.

At least 1,225 records · Page 68Linked to original sources

Cognitive functions in migraine without aura between attacks: a psychophysiological approach using the "oddball" paradigm.

"Oddball" paradigm studies of auditory P300 have yielded conflicting results in migraine. We therefore undertook an additional study of auditory event-related potentials (ERPs) using an improved method of EEG processing, strict criteria for patients selection, and comparison with behavioral data. Twenty-one healthy subjects were compared to 20 patients suffering from migraine without aura between attacks. Migraine patients differed significantly from control subjects on several parameters: shorter latency of N1 (Cz) evoked by standard stimuli, longer latencies of both P3a and P3b (Pz) evoked by target stimuli, longer interval between N1 and P3b (Cz), smaller P3b (Cz) amplitude, longer reaction time (RT), higher number of errors (false alarm and/or omissions) and higher mean score on Plutchik-Van Praag's (PVP) inventory for depression. Errors were significantly correlated with RT and PVP scores. From a behavioral perspective, these results may suggest that patients suffering from migraine without aura between attacks display a higher level of arousal and more superficial attention, but require more time for automatic and/or voluntary processes. According to the inverted U-shaped relationship between performance and arousal, these patients may have difficulties in adjusting their attention level to perform a task in a optimal way.

Adult↗

Risk of recurrent stroke in patients with sickle cell disease treated with erythrocyte transfusions.

OBJECTIVE: To determine the effect of a transfusion program on risk of stroke recurrence in children with sickle cell disease. DESIGN: The clinical course and experience with transfusion therapy at eight centers were reviewed for subjects whose initial stroke occurred after January 1988. RESULTS: Sixty subjects were observed for 191.7 patient-years. Eight had a single recurrent stroke (two intracranial hemorrhages and six infarctions) for a prevalence of 13.3%, or one recurrence for each 24 patient-years of observation. Thirteen subjects had 15 transient neurologic events; two of these had subsequent strokes, but the overall risk was similar for those who did and those did not have transient events. Hemoglobin S levels were greater than the desired maximum of 30% at the time of 7 of 16 transient events and five of six recurrent infarctions. The stroke recurrence rate was similar to those in previous reports of children receiving long-term transfusion therapy but significantly less than that reported for children who did not receive transfusions (p < 0.001). CONCLUSIONS: We conclude that maintenance of hemoglobin S at a level less than 30% appears to be effective in reducing the rate of recurrent infarction but does not prevent transient neurologic events. Transient neurologic events are common but do not appear to be related to recurrent stroke.

Adolescent↗

Quantitative electroencephalography: a method to assess cerebral injury after hypothermic circulatory arrest.

Although hypothermic circulatory arrest and low-flow cardiopulmonary bypass are routinely used for surgical correction of congenital cardiac anomalies, use of long durations of arrest, often required for more complex repairs, raises serious concerns about cerebral safety. Searching for an intraoperative assessment that can reliably predict cerebral injury, we have found an excellent correlation between changes in quantitative electroencephalography intraoperatively and immediately postoperatively after prolonged hypothermic arrest, and neurologic and behavioral evidence of cerebral injury. After epidural placement of four recording electroencephalographic electrodes and baseline neurologic/behavioral and electroencephalographic assessment, 32 puppies were randomly assigned to one of four groups: hypothermic controls in which cooling to 18 degrees C was followed immediately by rewarming, 30 minutes of hypothermic circulatory arrest at 18 degrees C, 90 minutes of arrest at 18 degrees C, and 90 minutes of low-flow cardiopulmonary bypass at 25 ml/kg per minute at 18 degrees C. An electroencephalogram was recorded at baseline, after cooling, during rewarming, and at 2, 4, and 8 hours after the start of rewarming, as well as before the operation and 1 week after the operation. Postoperative neurologic and behavioral outcome was assessed 24 hours after cardiopulmonary bypass and daily for 1 week by means of a graded scale in which 0 is normal and 12 and 13 indicate severe neurologic injury (coma and death). Thirty animals survived the experimental protocol: two animals in the 90-minute hypothermic arrest group died before neurologic evaluation could be completed, and the remainder exhibited various degrees of neurologic and behavioral impairment, more severe on day 1 than on day 6. No animal in the remaining groups had a significant neurologic deficit. Quantitative electroencephalographic analysis shows marked differences between the 90-minute arrest group and the controls in the percent electroencephalographic silence during rewarming and at 2 hours, and in the percent recovery of baseline power at 2, 4, and 8 hours. At 2 hours after the start of rewarming, a correlation between electroencephalographic amplitude and neurologic/behavioral score on day 1 was carried out, which predicts with great certainty (p < 0.00001) that if electroencephalographic power at this time is less than 500 microV2, overt neurologic injury will subsequently become apparent. In addition, a significant shift from higher to lower frequency in the day 6 postoperative electroencephalogram compared with baseline occurs only in the 90-minute arrest group.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Synergetic effects of epidermal growth factor and gonadotropins on the cytoplasmic maturation of pig oocytes in a serum-free medium.

Cumulus-enclosed or cumulus-free pig oocytes were cultured for 48 h in a serum-free maturation medium, TCM-199B containing 1 mg/ml polyvinylalcohol, supplemented with gonadotropins (PMSG + hCG) and/ or epidermal growth factor (EGF), and inseminated with frozen-thawed ejaculated spermatozoa. Fourteen hours after insemination, the ability of oocytes to form male pronucleus (MPN) was examined. EGF significantly increased the ability of cumulus-enclosed oocytes to form MPN irrespective of the concentrations (1-100 ng/ml) tested. Gonadotropins had a greater effect than EGF on MPN formation in cumulus-enclosed oocytes, and a synergetic effect was observed when EGF and gonadotropins were added together. However, neither EGF nor gonadotropins exhibited a stimulatory effect on MPN formation in cumulus-free oocytes. These results indicate that the role(s) of both EGF and gonadotropins in stimulating cytoplasmic maturation of pig oocytes is mediated by cumulus.

Animals↗

The Grb2 binding domain of mSos1 is not required for downstream signal transduction.

Cellular Ras proteins are activated primarily by specific guanine-nucleotide releasing factors such as the Son of Sevenless (Sos) proteins. This activation event is thought to occur in response to plasma membrane localization of a complex containing Sos and a small adapter protein Grb2. We have isolated a dominant mutant allele of mSos1 which transforms Rat1 cells, yet is no longer able to bind Grb2. Biochemical experiments reveal that the subcellular distribution of this truncated Sos protein is not altered with respect to the wild type Sos protein. These data argue against a role for Grb2 in the direct recruitment of Sos proteins to the plasma membrane and suggest that Grb2 may function to overcome negative regulation of Sos by its C terminus.

Adaptor Proteins, Signal Transducing↗

Clinical neurophysiology and neurotransmitters.

Clinical neurophysiology allows non-invasive assessment of neurotransmitter function in various regions of the central and peripheral nervous system. In this review, we describe examples of functional evaluation of neurotransmission at the neuromuscular junction, in some spinal interneurons and intracortical circuits as well as evaluation of pharmacological modulation of some electrophysiological tests. These investigations are carried out to help our understanding of the pathophysiology of brain diseases. Finally, we discuss possible relationships between electrophysiological tests (evoked/event-related potentials and exteroceptive suppression of temporalis muscle activity) and neurotransmitter function in headache.

Central Nervous System↗

Proliferative response of mammary glandular tissue to formononetin.

Dietary phytoestrogens have been implicated in infertility among ruminants and may relate to human breast cancer risk. Formononetin is an isoflavonoid phytoestrogen found in animal fodder and in certain human foodstuffs. To investigate a possible mechanism by which phytoestrogens might influence mammary carcinogenesis, this study examined the capacity of formononetin to stimulate mammary gland proliferation. Formononetin was administered to castrated female BALB/c mice by daily subcutaneous injection; then mammary gland proliferation and estrogen receptor expression were quantified, and plasma prolactin levels were measured. A preliminary dose-finding study demonstrated an estrogenic effect on vaginal cytology when formononetin was injected at 40 mg/kg sc. Peak plasma concentrations of 2.5 +/- 0.8 (SD) micrograms/ml at two hours and peak mammary tissue concentrations of 2.0 +/- 0.2 ng/mg tissue at four hours were noted after a single injection at this minimally bioactive dose. Among animals treated with formononetin at 40 mg/kg/day for five days, mammary gland proliferation was enhanced 3.3-fold over saline-treated controls and was comparable to that of animals treated with estradiol-17 beta at 1 microgram/kg/day for five days. Mammary tissue estrogen receptor expression was 2-fold higher among the formononetin-treated animals (P < 0.01 vs. saline-treated controls), and plasma prolactin concentrations were increased 1.7-fold (P < 0.001 vs. saline-treated controls). In subsequent in vitro binding studies, formononetin competitively bound murine mammary estrogen receptors, but with a relative binding affinity 15,000 times less potent than that of estradiol-17 beta. The results demonstrate an ability of formononetin to support mammary gland proliferation. However, the estrogenic potency of formononetin appears extremely weak compared with that of estradiol-17 beta and is roughly proportional to estrogen receptor-binding capacity.

Animals↗

The impact of outlying subjects on decision of bioequivalence.

As a consequence of a hearing on bioequivalence conducted by the Food and Drug Administration in 1986, the identification and the treatment of a potential outlier in bioequivalence trials has become an important issue in the assessment of bioequivalence because the exclusion of a statistically identified outlier may lead to a totally different conclusion on bioequivalence. In this paper, we examine the impact of a statistically identified outlying subject on the decision of bioequivalence through a simulation study under the structure of a standard two-way crossover design based on interval hypotheses for bioequivalence. The Hotelling T2 test suggested by Liu and Weng (1) is used for detection of an outlying subject.

Cross-Over Studies↗

On likelihood distance for outliers detection.

The likelihood distance has been widely used to detect outlying observations in data analysis. Cook and Weisberg (5) suggested that the likelihood distance may be compared to a chi 2 distribution for large samples. In this paper, we show that use of the chi 2 distribution is inappropriate. The results indicate that the likelihood distance does not follow an asymptotically chi 2 distribution. Instead, it converges to 0 in probability as the sample size increases. We show that for a nondegenerate limiting distribution, a multiplication factor related to the sample size n is needed. In general, the limiting distribution of this modified statistic is model-dependent.

Data Interpretation, Statistical↗

Effect of arachidonic acid on activity of the apical K+ channel in the thick ascending limb of the rat kidney.

We have used patch-clamp techniques to study the effects of arachidonic acid (AA) on the activity of the 70-pS K+ channel, the predominant type of the two apical K+ channels operating under physiological conditions in the thick ascending limb (TAL) of the rat kidney. Addition of 5-10 microM AA blocked the activity of the 70-pS K+ channel in both cell-attached and inside-out patches. The inhibitory effect of AA was specific, because application of 10 microM linoleic acid, oleic acid, or palmitic acid failed to mimic the effect of AA. The effect of AA could not be blocked by pretreatment of the TAL tubules with either 5 microM indomethacin (inhibitor of cyclooxygenase) or 4 microM cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate (CDC) (inhibitor of lipooxygenase). In contrast, addition of 5 microM 17-octadecynoic acid (17-ODYA), an inhibitor of P450 monooxygenases, abolised the effect of AA on the channel activity, indicating that the effect was mediated by cytochrome P450 metabolites of AA. Addition of 10 nM 20-hydroxyeicosatetraenoic acid (20-HETE), the main metabolite of the cytochrome P450 metabolic pathway in the medullary TAL, mimicked the inhibitory effect of 10 microM AA. However, addition of 100 nM 19-HETE or 17-HETE had no significant effects and 100 nM 20-carboxy AA (20-COOH) reduced the channel activity by only 20%, indicating that the inhibitory effect of 20-HETE was specific and responsible for the action of AA. Inhibition of the P450 metabolic pathway by either 5 microM 17-ODYA or 12, 12-dibromododec-11-enoic acid (DBDD) dramatically increased the channel activity by 280% in cell-attached patches. The stimulatory effect of 17-ODYA or DBDD was not observed in inside-out patches. The results strongly indicate that 20-HETE is a specific inhibitor for the 70-pS K+ channel and may play an important role in the regulation of the K+ channel activity in the TAL.

Animals↗

Measured and expected Cole parameters from electrical impedance tomographic spectroscopy images of the human thorax.

Electrical impedance tomographic spectroscopy (EITS) images have been recorded from a group of 12 normal subjects using frequencies from 9.6 kHz to 1.2 MHz. The impedance changes with frequency have been modelled on a pixel by pixel basis to produce parametric images as a means of characterizing tissue. The modelling was based on the Cole equation. The lungs are seen as areas of high characteristic frequency and low time constants SC and RS. The R/S images are much less uniform over the region of the lungs. Values characterizing the lung and cardiac regions are given. The results appear to be consistent with a model for the lungs whereby the model parameters can be related to alveolar structure and composition.

Adult↗

Systemic toxicology and laser safety of laser targeted angiography with heat sensitive liposomes.

Angiography is currently limited by its lack of local and tissue specificity. The dye rapidly fills both the retinal and choroidal vessels and leaks out of the vessels thus hampering visualization of small vascular beds such as occult choroidal neovascularization. We have developed a method of laser targeted delivery based on encapsulating the dye in heat sensitive liposomes, administering the liposomes intravenously and causing them to release their content by noninvasively warming the target tissue with a laser pulse delivered through the pupil. The local release yields a bright fluorescent bolus which selectively highlights retinal or choroidal vessels. A preliminary investigation of the potential side effects of the method is presented. In rats the systemic toxicity of carboxyfluorescein-entrapped liposomes was compared with that of the free dye. No significant difference was found between the two. Non-human primates exposed to repeated laser targeted angiography were monitored over time and no significant side effects were observed. The safety of the laser exposures was assessed by conventional fluorescein angiography and histopathology. Choroidal laser targeted angiography was achieved without damage. Retinal laser targeted angiography was accompanied by mild and local damage in an area remote from the fovea. The study indicates that laser targeted choroidal angiography can be performed safely and holds promise for diseases such as age related macular degeneration with occult choroidal neovascularization. Further improvements are needed to ensure that no side effects accompany retinal laser targeted angiography.

Animals↗

A longitudinal study of granulocyte colony-stimulating factor levels and neutrophil counts in newborn infants.

PURPOSE: The goal of this study was to longitudinally measure endogenous granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in newborn infants and to attempt to correlate these levels with neutrophil counts. PATIENTS AND METHODS: Samples for complete blood count, G-CSF, and GM-CSF were obtained from groups of healthy full-term infants at 0 (cord blood or nursery admission), 12, 24, 48, and 72 h. Samples were also obtained from premature infants at the above times and at 1 week. G-CSF and GM-CSF levels were measured using bioassays. RESULTS: Levels of G-CSF ranged from < 5 to 53,800 pg/ml. Levels were significantly higher (p < 0.001) in premature infants and decreased over time in all infants. White blood cell counts also decreased over the first week of life. All GM-CSF levels were below the detectable range. CONCLUSIONS: Levels of G-CSF at birth are higher than those seen in adults. These increased levels may partially explain the leukocytosis seen in the first week of life. This, as has been shown in preliminary studies, suggests that infants are capable of an increase in neutrophil count after administration of exogenous G-CSF.

Cell Cycle↗

Magnetically induced currents in the canine heart: a finite element study.

A moderately detailed three-dimensional (3-D) finite element model of the conductive anatomy of a canine thorax was used to determine the fields and currents induced by a time-varying magnetic field that has been shown to cause irregular heart beats in canines. The 3-D finite element model of the canine thorax was constructed from CT scans and includes seven isotropic tissue conductivities and the anisotropic conductivity of skeletal muscle. We use this model to estimate the stimulation threshold associated with stimulation of the heart by the time-varying magnetic field of a figure-eight coil. Variants of the thoracic model were also constructed to examine the sensitivity of model results to variations in model size, shape, and conductive inhomogeneity and anisotrophy. Our results show that myocardial fields were only midly sensitive to thoracic size. However, model shape and conductive inhomogeneity and anisotrophy substantially influenced the magnitude and distribution of myocardial fields and currents. Our results suggest that an induced peak field magnitude of approximately 1 V/cm is required to stimulate the heart with the magnetic excitation simulated in this study.

Animals↗

A flow cytometric assay using mepacrine for study of uptake and release of platelet dense granule contents.

Diagnosis of platelet dense granule storage pool disease and release defects at present requires a combination of studies including lumiaggregometry, conventional platelet aggregation, radioactive serotonin uptake and release, and electron microscopy. Flow cytometric methods have been developed to study platelet activation, aggregation, and alpha-granule protein release. Here, we have investigated the use of flow cytometry for analysis of platelet dense granule content uptake and release using mepacrine as a fluorescent marker. Mepacrine (quinacrine) is rapidly taken up and localized in dense granules of platelets. For the assay, as little as 20 microliters of blood from a fingerstick collected without anticoagulant or venous blood collected in 3.8% sodium citrate were diluted 1:40 with 2 ml Hanks balanced salt solution (BSS). 300 microliters of this cell suspension were incubated with mepacrine alone, or simultaneously with a mouse monoclonal antibody to human platelet glycoprotein IIb (Tab), used as a platelet-specific marker. The bound monoclonal antibody was then indirectly labelled with the fluorochrome, RED670. 100 microliters of the sample were further diluted with Hanks BSS for one- or two-colour flow cytometric analysis. To verify that mepacrine uptake was related to platelet dense granule content, platelets of beige mice, a strain with dense granule deficiency, were examined. Their mepacrine uptake was substantially decreased compared to that of normal mice. Decreased mepacrine uptake also was demonstrated in platelets of a patient with Hermansky-Pudlak syndrome in which a deficiency of platelet dense granules is characteristic. In both human and mouse platelets, mepacrine uptake was proportional to platelet size. Thrombin induced mepacrine release in a dose-dependent manner from 0.003 to 0.4 U/ml. Therefore both platelet uptake and release of mepacrine can be readily detected by flow cytometry. Flow cytometry provides an attractive alternative to aggregation and radioactive serotonin as methods to study defects in platelet dense granule function.

Animals↗

Specificity and sensitivity of temporalis ES2 measurements in the diagnosis of chronic primary headaches.

We have evaluated the specificity and sensitivity of temporalis ES2 measurements for the diagnosis of primary headaches. Ninety-four outpatients diagnosed according to IHS criteria were prospectively included: 25 had chronic tension-type headache (code 2.2.), 15 episodic tension-type headache (code 2.1.), 20 migraine without aura (code 1.1.) and 34 chronic daily headaches with daily analgesics/ergotamine abuse (code 8.2.). In chronic tension-type, the sensitivity of the ES2 test was 84% at the 0.1 and the 0.5 Hz, but only 56% at the 2Hz stimulation rates. Its specificity was 100% at 0.1Hz, 90% at 0.5Hz and 95% at 2Hz compared to migraine; positive predictive values were at similar levels. Sensitivity of ES2 at 0.1 Hz was 67% in episodic tension-type headache, but its positive predictive value versus migraine was excellent. Comparing chronic tension-type headache and analgesic abusers, the specificity and positive predictive value of the ES2 test for diagnosing chronic tension-type headache were less satisfactory (60%) while the negative predictive values, however, remained good (83% at 0.1Hz). The results confirm that the temporalis ES2 test has a higher diagnostic sensitivity in chronic and episodic tension-type headache, but that it has a high negative predictive value for both types of tension-type headache compared to other primary headaches. For diagnostic purposes, the 0.1Hz stimulation rate seems optimal. The 2Hz stimulation rate is the least sensitive, although it may induce total disappearance of ES2 in up to 40% of patients. ES2 is of limited usefulness for separating chronic tension-type headache and chronic drug-abuse headache, possibly because the latter group comprises both tension-type headache and migraine patients.

Chronic Disease↗