Search PubMed⌕ Search

Biomedical subjects

S Hu

Publications and source records attributed to S Hu.

At least 145 records · Page 8Linked to original sources

Brain energy stores in C57BL/6 mice after C. parvum injection.

Activation of the immune system has been associated with the development of fatigue of unknown cause. We were interested in brain energy stores (e.g., phosphocreatine (PCr) and creatine kinase) after immune activation to investigate whether this system was altered. In this model, fatigue (defined as > 50% reduction in spontaneous running) was induced in C57BL/6 mice after a single injection of Corynebacterium parvum antigen. Maximal fatigue (about 86% reduction on day 10 post injection) was associated with reduced (about 29%) brain PCr/gamma-ATP and increased creatine kinase levels (approximately 31%), suggesting an active process of brain ATP depletion and replenishment. These findings need to be further delineated to establish the relationship between immune activation, reduced brain energy pools and fatigue.

Animals↗

Neural androgen receptor regulation: effects of androgen and antiandrogen.

Androgens exert profound effects on the organization and function of the central nervous system. These effects are mediated by the androgen receptor (AR), a ligand-dependent transcription factor. The mechanisms of AR regulation in neural tissue, however, remain to be fully elucidated. Characterizing this process can provide important information regarding receptor function and AR gene regulation in the brain. Previously, it was shown that testosterone (T) up-regulated neural AR in a dose-dependent manner in both male and female mice. In the present study, whether AR was differentially regulated by the natural agonists T and dihydrotestosterone (DHT) or the nonsteroidal antagonist flutamide (FLU) was assessed. Males were gonadectomized and AR levels were allowed to decline to baseline 3 days after surgery. Changes in AR protein content produced by the various treatments were measured by semiquantitative Western blot of limbic system extracts. Treatment with T or DHT significantly augmented AR 3 and 7 h after hormone administration, but only DHT sustained this increase for 21 h. This difference also was observed when males were given T plus finasteride (FIN, a 5alpha reductase inhibitor). The findings demonstrate that the two endogenous ligands have differential time course effects on neural AR. The antiandrogen FLU failed to up-regulate AR at doses up to 100 times higher than T or DHT. When administered concomitantly with T or DHT, it effectively inhibited the augmentation of AR normally seen 3 h after androgen treatment. While immunohistochemical studies showed that FLU was able to promote nuclear translocation of AR, Western analysis revealed that FLU, in contrast to T and DHT, failed to maintain the integrity of AR. The results demonstrate that (a) the endogenous androgens T and DHT regulate AR differently, suggesting a potential cellular mechanism that may contribute to the difference in neural target gene sensitivity to these androgens; (b) up-regulation of AR occurs only in the presence of agonists; (c) the mechanism of action of FLU in the brain involves inhibition of AR protein up-regulation normally seen in response to androgen; and (d) FLU promotes AR nuclear translocation but not augmentation of cellular AR populations. These findings demonstrate that in vivo AR regulation in the brain basically parallels mechanisms proposed from results obtained with transfected cells and cell lines.

Androgen Antagonists↗

Inhibition of microglial cell RANTES production by IL-10 and TGF-beta.

Using human fetal microglial cell cultures, we found that the gram-negative bacterial cell wall component lipopolysaccharide (LPS) stimulated RANTES (regulated upon activation of normal T cell expressed and secreted) production through the protein kinase C signaling pathway and that activation of transcription nuclear factor (NF)-kappaB was required for this effect. Similarly, the proinflammatory cytokines interleukin (IL)-1beta and tumor necrosis factor-alpha dose-dependently stimulated microglial cell RANTES production via NF-kappaB activation. Anti-inflammatory cytokines, IL-10, and transforming growth factor (TGF)-beta sequentially inhibited LPS- and cytokine-induced microglial cell NF-kappaB activation, RANTES mRNA expression, and protein release. Proinflammatory cytokines but not LPS also stimulated RANTES production by human astrocytes. These findings demonstrate that human microglia synthesize RANTES in response to proinflammatory stimuli, and that the anti-inflammatory cytokines IL-10 and TGF-beta down-regulate the production of this beta-chemokine. These results may have important therapeutic implications for inflammatory diseases of the brain.

Cell Lineage↗

Variable forms of soluble guanylyl cyclase: protein-ligand interactions and the issue of activation by carbon monoxide.

Soluble guanylyl cyclase (sGC) is known to be activated by NO binding to the heme moiety; previous studies have shown that CO does not activate sGC to the same extent as NO. Resonance Raman spectroscopy reveals different heme pocket structures for soluble guanylyl cyclase prepared by alternate methods, all of which display activation by NO. In our preparation, and in the expressed protein sGC1, the resting Fe(II) state is mainly 6-coordinate and low-spin, and the CO adduct has vibrational frequencies characteristic of a histidine-heme-CO complex in a hydrophobic environment. In contrast, the protein sGC2 is 5-coordinate, high-spin in the resting state, and the CO adduct has perturbed vibrational frequencies indicative of a negatively polarizing residue in the binding pocket. The differences may result from the need to reconstitute sGC1 or different isolation procedures for sGC1 versus sGC2. However, both sGC1 and sGC2 are activated by the same mechanism, namely displacement of the proximal histidine ligand upon NO binding, and neither one is activated by CO. If CO is an activator in vivo, some additional molecular component is required.

Animals↗

Factors related to adiposity among children aged 3 to 7 years.

OBJECTIVE: To compare diet and physical activity between a group of children aged 4 to 7 years who had increased their sum of 7 skinfolds by 1.5 standard deviations or more since the previous year and those who had not. SUBJECTS/DESIGN: A longitudinal design was used wherein children had their body composition assessed at 4 annual intervals. Fifteen study subjects were identified from a larger study on the development of cardiovascular risk factors in children. Three matched control subjects were identified for all but 4 study subjects. Children were included if they were 3 or 4 years old at the time of the first of 4 annual clinics to collect data. Children were volunteers from a mid-sized city. MEASURES: Seven skinfold sites were assessed, each 3 times. An average was taken of the mean at each site. Diet and physical activity were assessed using observational methods for up to 4 days for each of 3 years between the 4 annual clinics (held in the summers of 1986, 1987, 1988, and 1989). RESULTS: Children consumed significantly (P = .02) more fat grams and suggestively higher percentages of energy from fat (P = .06), total energy (P = .08), and percentage energy from protein (P = .10). No differences were detected for percent energy from carbohydrate, physical activity, or height. CONCLUSIONS: Programs to prevent childhood obesity might have success by targeting dietary fat consumption among children as young as 4 years old, but further research is needed.

Adipose Tissue↗

Endomorphin-1 potentiates HIV-1 expression in human brain cell cultures: implication of an atypical mu-opioid receptor.

Endogneous delta and kappa opioid peptides possess a variety of immunomodulatory properties, and kappa-opioid receptor ligands recently were shown to suppress the expression of human immunodeficiency virus type 1 (HIV-1) in microglial cells, the resident macrophages of the brain. To determine whether the newly discovered endogenous mu-opioid receptor ligands endomorphin-1 and -2 would affect HIV-1 replication, these peptides were added to acutely infected brain cell cultures. Endomorphin-1 potentiated viral expression, in a bell-shaped dose-response manner with maximal enhancement approximately equal to 35% at 10(-10) M, in both mixed glial/neuronal cell and purified microglial cell cultures. Endomorphin-1's amplifying effect was blocked by pretreatment of brain cells with either the mu-opioid receptor selective antagonist beta-funaltrexamine or the G protein inhibitor pertussis toxin. However, the classical mu receptor agonists morphine and DAMGO (Tyr-d-Ala-Gly-N-Me-Phe-Gly-ol) had no effect on viral expression or on endomorphin-1's amplifying effect. Taken together, these findings suggest that in this in vitro model of HIV-1 brain infection, endomorphin-1 potentiates viral expression via activation of an atypical mu-selective opioid receptor. They also provide evidence, for the first time, that an endogenous mu-opioid peptide has neuroimmunomodulatory activity.

Analgesics, Opioid↗

Long-term reversal of hemispheric specialization for visual memory in a split-brain macaque.

Accuracy of response and pattern of ocular fixations in three split-brain macaques were used to evaluate performance of each hemisphere in a continuous visual recognition task. The animal indicated by ocular fixation upon response points whether a displayed image or face was 'NEW' or 'OLD'. An inadvertent lesion of cingulate gyrus severely reduced contralateral fixations and impaired performance of the affected hemisphere in one animal, confirming the inferred relation between hemisphere and laterality of fixations. The hemispheres in the other two animals were initially remarkably similar in accuracy with human faces and with images; but the right hemisphere was significantly superior to the left for macaque faces. Parallel to this, in the one animal tested while simultaneously using both eyes/hemispheres, fixations were made primarily on the left half of human and macaque faces (right hemispheric control), whereas for images the ocular fixations were predominantly focused on the right half. However, after further, extensive training the left hemisphere performed with significantly greater accuracy than the right on all material and this shift was accompanied and further corroborated by a reversal of the fixational pattern to favor the right half of faces, as continued to be the case with images. Thus, over the long term both the pattern of ocular fixations and the accuracy of performance demonstrate a migration from right to left hemispheric dominance as familiarity with the task increased. Performance of the initially superior hemisphere actually diminished with this shift, presenting a uniquely puzzling question of hemispheric balance in the absence of the forebrain commissures.

Animals↗

Soil microbial feedbacks to atmospheric CO2 enrichment.

Increased atmospheric CO2 concentration often stimulates plant photosynthesis, enhances carbon (C) allocation below-ground, increases plant nutrient uptake and improves the efficiency of plant water use. Recent studies suggest that microbial responses to CO2-induced alterations in soil C, water and nutrient availability play an important role in determining ecosystem feedback to CO2 elevation. However, to date, most of the published results have been obtained from short-term experiments or from studies using high-nutrient or disturbed soils. Information on microbial responses to CO2-induced changes in natural and/or mature ecosystems with nutrient limitations is critical to predict changes in terrestrial ecosystem C storage under future CO2 scenarios.

Journal Article↗

A genetic association for cigarette smoking behavior.

Dopaminergic genes are likely candidates for heritable influences on cigarette smoking. In an accompanying article, Lerman et al. (1999) report associations between allele 9 of a dopamine transporter gene polymorphism (SLC6A3-9) and lack of smoking, late initiation of smoking, and length of quitting attempts. The present investigation extended their study by examining both smoking behavior and personality traits in a diverse population of nonsmokers, current smokers, and former smokers (N = 1,107). A significant association between SLC6A3-9 and smoking status was confirmed and was due to an effect on cessation rather than initiation. The SLC6A3-9 polymorphism was also associated with low scores for novelty seeking, which was the most significant personality correlate of smoking cessation. It is hypothesized that individuals carrying the SLC6A3-9 polymorphism have altered dopamine transmission, which reduces their need for novelty and reward by external stimuli, including cigarettes.

Adult↗

Green and yellow vegetables can maintain body stores of vitamin A in Chinese children.

BACKGROUND: Vitamin A activity of plant provitamin A carotenoids is uncertain. OBJECTIVE: The objective was to determine whether plant carotenoids can sustain or improve vitamin A nutrition during the fall season in kindergarten children in the Shandong province of China. DESIGN: The serum vitamin A concentration of 39% of the children was <1.05 micromol/L and of 61% of the children was > or = 1.05 micromol/L. For 5 d/wk for 10 wk, 22 children were provided approximately 238 g green-yellow vegetables/d and 34 g light-colored vegetables/d. Nineteen children maintained their customary dietary intake, which included 56 g green-yellow vegetables/d and 224 g light-colored vegetables/d. Octadeuterated and tetradeuterated vitamin A were given before and after the interventions, respectively, and their enrichments in the plasma were determined by gas chromatography-mass spectrometry. Serum retinol and carotenoid concentrations were measured by HPLC. RESULTS: Carotenoid nutrition improved after consumption of green-yellow vegetables. Serum concentrations of retinol were sustained in the group fed green-yellow vegetables but decreased in the group fed light-colored vegetables (P < 0.01). The isotope-dilution tests confirmed that total-body vitamin A stores were sustained in the group fed green-yellow vegetables, but decreased 27 micromol (7700 microg retinol) per child, on average, in the group fed light-colored vegetables (P < 0.06). CONCLUSION: Green-yellow vegetables can provide adequate vitamin A nutrition in the diet of kindergarten children and protect them from becoming vitamin A deficient during seasons when the provitamin A food source is limited.

Analysis of Variance↗

Effects of semantic discrimination of Chinese words on N400 component of event-related potentials.

20 subjects' event-related brain potentials were measured during a lexical decision task in which Chinese characters were used in both conditions of related (antonym) and unrelated words. Analysis indicated that the mean reaction time for unrelated words was 130 msec. longer than that elicited by related words. The condition of unrelated words elicited a significant N450, and an obvious P500 was evoked by related words at each of the 17 recording sites. Furthermore, the amplitudes of N210 and N450 were larger in the left hemisphere than in the right hemisphere but the amplitude of P500 was larger in the right hemisphere than in the left hemisphere.

Adolescent↗

Systematic investigation of physiological correlates of motion sickness induced by viewing an optokinetic rotating drum.

PURPOSE: This study investigated the physiological correlates of motion sickness provoked by viewing an optokinetic rotating drum. METHOD: A total of 52 subjects viewed an optokinetic rotating drum for 16 min. Subjective symptoms of motion sickness (SSMS) and ratings of over-all sickness were measured during the drum rotation. Electrogastrogram (EGG), electroencephalogram (EEG), electrocardiogram, and skin conductance were measured as physiological correlates of motion sickness. RESULTS: Analysis by Pearson's correlation showed that the subjects who had higher scores of SSMS during the drum rotation generated the following: a) a higher rating of over-all sickness (r = 0.76); b) a higher ratio of spectral power of EGG at 4-9 cycles per minute (cpm) between drum rotation and baseline periods (r = 0.63); c) a higher net percent increase of spectral power in the EEG frequency band 0.5-4 Hz between drum rotation and baseline periods on C3 (r = 0.29) and C4 (r = 0.31); d) a higher ratio of spectral power of EEG frequency band 0.5-4 Hz between drum rotation and baseline periods on C3 (r = 0.31); and e) a higher level of net increase in skin conductance from baseline to drum rotation (r = 0.30). CONCLUSION: The increase of EGG at 4-9 cpm activity, gastric tachyarrhythmia, is the most sensitive physiological index of the severity of symptoms of motion sickness.

Adolescent↗

The retention of adaptation to motion sickness eliciting stimulation.

PURPOSE: This study compared the retention of adaptation to motion sickness eliciting stimulation after 1 mo and 1 yr. METHOD: A total of 34 subjects who developed nausea to an optokinetic rotating drum in a preliminary session repeatedly viewed the same rotation with an interval of 48 h between sessions until they had no feelings of nausea. For each session, subjects' electrogastrograms (EGGs) at 4-9 cycles per minute (cpm) were also recorded as a physiological index of the severity of motion sickness. Subjects were re-exposed to the optokinetic drum either after 1 mo or 1 yr. RESULTS: The mean ratings of nausea for the subjects who were re-exposed to the optokinetic drum after 1 mo were 9.23 for the initial exposure and 0.94 for the re-exposure session. EGG indicators of motion sickness were 6.65 for the initial exposure and 1.03 for the re-exposure session. The mean ratings of nausea for the subjects who were re-exposed to the optokinetic drum after 1 yr were 8.94 for the initial exposure and 6.88 for the re-exposure session. EGG indicators of motion sickness were 5.97 for the initial exposure and 4.05 for the re-exposure session. CONCLUSION: These results indicated that adaptation to the motion sickness eliciting stimulation of optokinetic rotation is almost completely retained for 1 mo and partially retained for 1 yr.

Adaptation, Physiological↗

Tissue selectivity of antidiabetic agent nateglinide: study on cardiovascular and beta-cell K(ATP) channels.

Nateglinide (NAT) stimulates insulin secretion from pancreatic beta-cells by closing K(ATP) channels. Because K(ATP) channels are widely distributed in cardiovascular (CV) tissues, we assessed the tissue specificity of NAT by examining its effect on K(ATP) channels in enzymatically isolated rat beta-cells, rat cardiac myocytes, and smooth muscle cells from porcine coronary artery and rat aorta with the patch-clamp method. The selectivity of known antidiabetic agents glyburide (GLY) and repaglinide (REP) was also studied for comparison. NAT was found to inhibit K(ATP) channels in the cells from porcine coronary artery and rat aorta with IC(50)s of 2.3 and 0. 3 mM, respectively, compared with 7.4 microM in rat beta-cells, indicating a respective 311- and 45-fold selectivity (p <.01) for beta-cells. With an IC(50) of 5.0 nM in beta-cells, REP displayed an approximately 16-fold (p <.05) selectivity for beta-cells over both types of vascular cells. GLY was nonselective between vascular and beta-cells. At equipotent concentrations (2x respective IC(50)s in beta-cells), NAT, GLY, and REP all caused 62% reduction of pancreatic K(ATP) current but a respective 39, 55, and 66% inhibition of cardiac K(ATP) current. These data collectively indicate that NAT, when compared with GLY and REP, at concentrations effective in stimulating insulin secretion is least likely to cause detrimental CV effects via blockade of CV K(ATP) channels.

Animals↗

Gender differences in motion sickness history and susceptibility to optokinetic rotation-induced motion sickness.

PURPOSE: The present study investigated gender differences in motion sickness history and susceptibility to optokinetic rotation-induced motion sickness. METHODS AND RESULTS: The study included two phases. In Phase 1, 485 subjects filled out a survey of previous incidence of motion sickness. Results indicated that women reported significantly greater incidence of feeling motion sickness than did men on buses, on trains, on planes, in cars, and on amusement rides before the age of 12 yr; and on buses, on trains, on planes, in boats, on ships, in cars, on amusement rides, and on swings between the ages of 12 and 25 yr. Women also reported significantly higher incidence of being actually sick than did men on buses before the age of 12 yr and on buses, on ships, and in cars between the ages of 12 and 25 yr. In Phase 2, each of the 47 subjects viewed an optokinetic rotating-drum for 16 min. Subjects' subjective symptoms of motion sickness (SSMS) were obtained during drum rotation. The results showed that there were no significant differences on SSMS scores between men and women. CONCLUSION: Although women reported greater incidence in motion sickness history, women did not differ from men in severity of symptoms of motion sickness while viewing a rotating optokinetic drum.

Adolescent↗

Ultrasound biomicroscopic study on changes of ocular anterior segment structure after topical application of cycloplegia.

OBJECTIVES: To observe the changes of the ocular anterior segment structure and the relationship between the intraocular pressure (IOP) and these changes after the topical application of cycloplegia using ultrasound biomicroscope (UBM), especially to observe the changes of ciliary body thickness, ciliary process thickness and ciliary process-lens distance. METHODS: The quantitative measurement with UBM and the measurement of IOP were performed before and after the topical application of 2% homatropine solution in 48 normal eyes. The results were statistically analyzed. RESULTS: In the parameters showing the changes of the anterior chamber angle after topical use of 2% homatropine solution, both the trabecular iris angle and the angle opening distance 250 decreased. The iris thickness 1 increased. The anterior chamber became deeper and the iris-lens contact distance became shorter. All these differences were statistically significant (P < 0.05). In the parameters showing the changes of ciliary body, the ciliary body thickness and the ciliary process thickness decreased. The scleral ciliary body angle increased. The iris-zonule distance decreased and the ciliary process-lens distance increased. All these differences were statistically significant (P < 0.05). The IOP increased from 17.63 +/- 3.45 mm Hg to 18.23 +/- 3.53 mm Hg after topical use of 2% homatropine solution, but the difference was not statistically significant (P > 0.05). CONCLUSIONS: After the topical use of cycloplegia, the anterior chamber becomes deeper. The anterior chamber angle becomes narrower, and the ciliary body becomes thinner and moves backward and the ciliary process-lens distance increases. By using UBM the structures of the ocular anterior segment in the living state can be observed and measured quantitatively. The ultrasound biomicroscopic imaging has its advantages in the morphological study of the ocular anterior segment.

Adult↗