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Biomedical subjects

W Wang

Publications and source records attributed to W Wang.

At least 307 records · Page 17Linked to original sources
PubMed2001

Downregulation of AQP1, -2, and -3 after ureteral obstruction is associated with a long-term urine-concentrating defect.

Previously, we demonstrated that 24 h of bilateral ureteral obstruction (BUO) and short-term release of BUO was associated with a decrease in the expression of aquaporin-2 (AQP2), polyuria, and a reduced urinary concentrating capacity (10). The purposes of the present study were to examine whether BUO and the long-term release of BUO (BUO-R) for 3, 14, and 30 days were associated with changes in the expression of renal AQP1, AQP2, and AQP3 and whether such changes were associated with parallel changes in urinary output and urinary concentrating capacity. Rats (n = 4-7 in each group) were kept in metabolic cages for measurements of urinary output. Kidneys were removed to determine the expression levels of AQP1, AQP2, and AQP3 by semiquantitative immunoblotting. AQP2 was downregulated after 24 h of BUO (42 +/- 3%). Downregulation of AQP2 persisted 3 (43 +/- 14%; P < 0.01) and 15 days after BUO-R (48 +/- 11%; P < 0.01) but was normalized 30 days after BUO-R. AQP3 showed a similar pattern. Moreover, AQP1 was downregulated in response to BUO (65 +/- 7%) and remained downregulated 3 days after BUO-R (41 +/- 5%), 14 days after BUO-R (57 +/- 8%), and 30 days after BUO-R (59 +/- 5%). BUO-R resulted in a significant polyuria that gradually decreased, although it remained significant at day 30. Urinary concentrating capacity remained significantly impaired when determined 3, 14, and 30 days after BUO-R in response to a 24-h period of thirst (1,712 +/- 270 vs. 2,880 +/- 91 mosmol/kgH2O at day 30, P < 0.05). In conclusion, the expression of AQP1, AQP2, and AQP3 were long-term downregulated after BUO-R, suggesting that dysregulation of aquaporins located at the proximal tubule, thin descending limb of the loop of Henle, and the collecting duct may contribute to the long-term polyuria and impairment of urinary concentrating capacity associated with obstructive nephropathy.

Animals↗
PubMed2001

Acidosis-stimulated neurons of the medullary raphe are serotonergic.

Neurons of the medullary raphe project widely to respiratory and autonomic nuclei and contain co-localized serotonin, thyrotropin-releasing hormone (TRH), and substance P, three neurotransmitters known to stimulate ventilation. Some medullary raphe neurons are highly sensitive to pH and CO(2) and have been proposed to be central chemoreceptors. Here it was determined whether these chemosensitive neurons are serotonergic. Cells were microdissected from the rat medullary raphe and maintained in primary cell culture for 13-70 days. Immunoreactivity for serotonin, substance P, and TRH was present in these cultures. All acidosis-stimulated neurons (n = 22) were immunoreactive for tryptophan hydroxylase (TpOH-IR), the rate-limiting enzyme for serotonin biosynthesis, whereas all acidosis-inhibited neurons (n = 16) were TpOH-immunonegative. The majority of TpOH-IR medullary raphe neurons (73%) were stimulated by acidosis. The electrophysiological properties of TpOH-IR neurons in culture were similar to those previously reported for serotonergic neurons in vivo and in brain slices. These properties included wide action potentials (4.55 +/- 0.5 ms) with a low variability of the interspike interval, a postspike afterhyperpolarization (AHP) that reversed 25 mV more positive than the Nernst potential for K(+), prominent A current, spike frequency adaptation and a prolonged AHP after a depolarizing pulse. Thus the intrinsic cellular properties of serotonergic neurons were preserved in cell culture, indicating that the results obtained using this in vitro approach are relevant to serotonergic neurons in vivo. These results demonstrate that acidosis-stimulated neurons of the medullary raphe contain serotonin. We propose that serotonergic neurons initiate a homeostatic response to changes in blood CO(2) that includes increased ventilation and modulation of autonomic function.

Acidosis↗
PubMed2001

Surround suppression in primate V1.

We investigated the spatial organization of surround suppression in primate primary visual cortex (V1). We utilized drifting stimuli, configured to extend either from within the classical receptive field (CRF) to surrounding visual space, or from surrounding visual space into the CRF or subdivided to generate direction contrast, to make a detailed examination of the strength, spatial organization, direction dependence, mechanisms, and laminar distribution of surround suppression. Most cells (99/105, 94%) through all cortical layers, exhibited suppression (mean reduction 67%) to uniform stimuli exceeding the CRF, and 43% exhibited a more than 70% reduction. Testing with an annulus revealed two different patterns of surround influence. Some cells (37% of cells), classical surround suppression (CSS) cells exhibited responses to an annulus encroaching on the CRF that were less than the plateau in the spatial summation curve. The majority (63%), center-gated surround suppression (CGSS) cells, showed responses to annuli that equaled or exceeded the plateau in the spatial summation curve. Analysis suggested the CSS mechanism was implemented in all cells while the CGSS mechanism was implemented in varying strength across the sample with the extreme reflected in cells that gave larger responses to annuli than to a center stimulus. Reversing the direction of motion of the portion of the stimulus surrounding the CRF revealed four different patterns of effect: no reduction in the degree of suppression (22% of cells), a reduction in surround suppression (41%), a facilitation of the response above the level to the inner stimulus alone (37%), and a facilitation of the response above that to the inner stimulus alone that also exceeded the values associated with an optimal inner stimulus. The facilitatory effects were only seen for reverse direction interfaces between the central and surrounding stimulus at diameters equal to or more than the CRF size. The zones driving the suppressive influences and the direction contrast facilitation were often spatially heterogeneous and for a number of cells bore strong comparison with the class of behavior reported for surround mechanisms in MT. This suggests a potential role, for example, in extracting information about motion contrast in the representation of the three dimensional structure of moving objects.

Animals↗
PubMed2001

PKA-induced stimulation of ROMK1 channel activity is governed by both tethering and non-tethering domains of an A kinase anchor protein.

We have used the patch-clamp technique to explore the role of A Kinase Anchor Proteins (AKAP) in mediating the effect of cAMP on ROMK1 channels expressed in the Xenopus oocytes. Addition of membrane permeant cAMP analogs increased channel activity only in oocytes injected with ROMK1 and AKAP79 cRNA but had no effect on channel activity in oocytes injected with ROMK1 alone. Using the two-electrode voltage clamp technique, we determined that application of H89, a potent inhibitor of protein kinase A (PKA), abolished the stimulatory effect of cAMP/forskolin. To investigate the role of AKAP specificity in conferring cAMP responses to ROMK1 channels, we examined channel activity in oocytes expressing ROMK1 and either AKAP18, AKAP-KL or AKAP75. Addition of cAMP failed to increase channel current in oocytes expressing ROMK1 and either AKAP18 or AKAP-KL. In contrast, cAMP increased ROMK1 channel activity by 33% in oocytes coexpressing AKAP75, the bovine homologue of AKAP79. The effect of cAMP on ROMK1 in oocytes coexpressing AKAP75 is inhibited by H89. Since all three AKAPs bind PKAII, the results suggest that a unique structural domain in AKAP75/79 collaborates with the PKAII binding site and enables a productive association of PKA with ROMK1 channels. Deletion of either the membrane targeting region of AKAP75 (AKAP45) or PKAII binding domain of AKAP75 (AKAP75DeltaC) abolished the effects of forskolin on ROMK1 channels. This suggests that the membrane targeting and the PKA binding domains of AKAP75 are essential for the effect of cAMP. However, the nature of the AKAP, that interacts with ROMK1 in the native tissue, remains to be determined because AKAP75/79 are not expressed in the kidney. We conclude that the regulation of ROMK1 channels by PKA requires the involvement of the cell membrane-directed AKAPs that are able to specifically link PKA to the target channel protein.

Animals↗
PubMed2001

Interleukin-18 is elevated in the sera from patients with atopic dermatitis and from atopic dermatitis model mice, NC/Nga.

BACKGROUND: Several lines of in vitro and in vivo studies have demonstrated that interleukin-18 (IL-18) shows both antiallergic and allergy-promoting activities. But its expression in allergic diseases remains unknown. METHODS: Serum IL-18 levels from atopic dermatitis (AD) model mice, NC/Nga and control mice and from patients with AD and healthy volunteers were measured by ELISA. The relationship between IL-18 levels and serum IgE levels or clinical severity was also examined. RESULTS: Serum IL-18 levels from NC/Nga mice were significantly increased compared to those from control mice. The elevation of IL-18 in the sera was observed prior to the onset and during the development of dermatitis in NC/Nga mice. In addition, IL-18 levels in the sera from patients with AD were significantly (p < 0.05) elevated compared to those from healthy volunteers. However, serum IL-18 levels tended to correlate negatively with serum IgE levels in patients with AD and NC/Nga mice. CONCLUSION: IL-18 is overexpressed in AD.

Adolescent↗
PubMed2001

Molecular cloning and characterization of a novel peptidylprolyl isomerase (cyclophilin)-like gene (PPIL3) from human fetal brain.

During the large-scale sequencing analysis of a human fetal brain cDNA library, we isolated two cDNA clones encoding two novel proteins, which show 52% and 72% identity to the cyclophilin isoform 10 of C. elegans, respectively. Sequence analysis revealed these two cDNA clones are two different splicing variants of a novel cyclophilin-like gene (PPIL3). The PPIL3 gene was identified on a completely sequenced BAC (GenBank accession AC005037) from chromosome 2q33 between STS markers stSG2762 (proximal) and SHGC-3074 (distal), oriented toward the telomere. The PPIL3 gene consisted of eight exons spanning more than 18 kb of genomic DNA. RT-PCR analysis indicated that PPIL3 was ubiquitously expressed in adult human tissues.

5' Untranslated Regions↗
PubMed2001

Molecular cloning, structure and expression of a novel nuclear RNA-binding cyclophilin-like gene (PPIL4) from human fetal brain.

The cyclophilins are members of a highly conserved, ubiquitous family, and play an important role in protein folding, immunosuppression by cyclosporin A (CsA), and infection of HIV-1 virions. Here we report that a novel member of the cyclophilin family, PPIL4, was cloned and identified during the large-scale sequencing analysis from a human fetal brain cDNA library. The PPIL4 gene encodes a protein which shares 96% amino acid identity with a protein encoded by a putative gene recently cloned from several different early stages of mouse embryo, and its homologues are found in several other organisms. According to bioinformatics analysis, the PPIL4 gene was found to be located in chromosome 6q24-->q25. Besides the PPIase motif, PPIL4 also has an RNA recognition motif (RRM), a pair of bipartite nuclear targeting sequences, and a lysine rich domain. RT-PCR analysis indicated that PPIL4 gene expression is abundant in kidney but has a ubiquitously low expression pattern in other human adult tissues.

Amino Acid Motifs↗
PubMed2001

A comparative study of feature-salience ranking techniques.

We assess the relative merits of a number of techniques designed to determine the relative salience of the elements of a feature set with respect to their ability to predict a category outcome-for example, which features of a character contribute most to accurate character recognition. A number of different neural-net-based techniques have been proposed (by us and others) in addition to a standard statistical technique, and we add a technique based on inductively generated decision trees. The salience of the features that compose a proposed set is an important problem to solve efficiently and effectively, not only for neural computing technology but also in order to provide a sound basis for any attempt to design an optimal computational system. The focus of this study is the efficiency and the effectiveness with which high-salience subsets of features can be identified in the context of ill-understood and potentially noisy real-world data. Our two simple approaches, weight clamping using a neural network and feature ranking using a decision tree, generally provide a good, consistent ordering of features. In addition, linear correlation often works well.

Accidents, Aviation↗
PubMed2001

STAT4 and STAT6 regulate systemic inflammation and protect against lethal endotoxemia.

Members of the signal transducer and activator of transcription (STAT) family are transcription factors that mediate many of the effects of pro- and anti-inflammatory cytokines. The progressive systemic inflammatory response induced by endotoxin is mediated by overzealous cytokine production. Here we identify STAT4 and STAT6 as critical regulators of the systemic inflammatory response to endotoxin. Mice deficient for STAT4 or STAT6 were highly susceptible to lethal endotoxemia. In STAT4(-/-) mice, antibody blockade of IL-12 prevented mortality, suggesting that STAT4 confers protection, while another signaling pathway mediates the detrimental effects of IL-12. In STAT6(-/-) mice we observed dysregulated activation of the transcription factor NF-kappaB, resulting in augmented production of proinflammatory cytokines and chemokines. Furthermore, STAT6(-/-) mice displayed increased organ accumulation of leukocytes and significant hepatocellular injury. These findings demonstrate that STAT4 and STAT6 confer protection against endotoxin-induced death and that for STAT6 these protective effects occur through the regulation of NF-kappaB activation and subsequent production of proinflammatory cytokines and chemokines.

Animals↗
PubMed2001

A clinical manifestation of AIDS with cryptococcal meningitis in Equatorial Guinea.

Eighteen cases of confirmed AIDS with cryptococcal meningitis in Bata Regional Hospital, Equatorial Guinea from January 1997 to November 1999 were analysed. The associated morbidity and mortality rates were very high. Contributory factors were the failure to note the occurrence of AIDS with cryptococcal meningitis, late presentation, serious illness and severe complications, and delayed and inadequate therapy.

AIDS-Related Opportunistic Infections↗
PubMed2001

Chinese students' concept of mental health.

This study explored Chinese students' concept of mental health through a questionnaire completed by 999 students from six primary schools, six high schools, and three universities in Shanghai. The results confirmed the expectation that Chinese students' mental health concept would be multifaceted and would reflect psychological, physical, and sociocultural factors. An exploratory factor analysis on 12 mental health items with a subsample extracted a three-factor model, which was cross-validated by confirmatory factor analysis with a different subsample. These three factors were labeled as Affective Strength, Adaptive Strength, and Personal Strength. No gender differences were found. The grade differences supported the notion that Chinese students' concept of mental health seems to be more consistent with the developmental paradigm of health. The senior years in primary school could be the turning point at which children start to conceptualize health as a holistic experience by recognizing the importance of mental health.

Adaptation, Psychological↗
PubMed2001

Sickle cell and the brain.

Sickle cell disease affects many organ systems, but one of the major morbidities is brain disease, especially stroke. In this paper, the etiology, diagnosis, treatment, and prevention of clinical stroke, as well as so-called "silent stroke," are examined. Risk factors, diagnostic tools, and data from prevention and treatment studies as well as issues pertaining to neuropsychological function, especially in younger patients, are discussed and current best options for treatment considered.

Age Factors↗
PubMed2001

Regulator of G protein signaling 4 suppresses basal and thyrotropin releasing-hormone (TRH)-stimulated signaling by two mouse TRH receptors, TRH-R(1) and TRH-R(2).

We cloned the mouse TRH receptor type 2 (mTRH-R2) gene, which is 92% identical with rat TRH-R2 and 50% identical with mTRH-R1 at the amino acid level, and identified an intron within the coding sequence that is not present in the TRH-R1 gene structure. Similar to its rat homolog, mTRH-R2 binds TRH with an affinity indistinguishable from mTRH-R1, signals via the phosphoinositide pathway like mTRH-R1, but exhibits a higher basal signaling activity than mTRH-R1. We found that regulator of G protein signaling 4 (RGS4), which differentially inhibits signaling by other receptors that couple to Gq, inhibits TRH-stimulated signaling via mTRH-R1 and mTRH-R2 to similar extents. In contrast, other RGS proteins including RGS7, RGS9, and GAIP had no effect on signaling by mTRH-R1 or mTRH-R2 demonstrating the specificity of RGS4 action. Interestingly, RGS4 markedly inhibited basal signaling by mTRH-R2. Inhibition of basal signaling of mTRH-R2 by RGS4 suggests that modulation of agonist-independent signaling may be an important mechanism of regulation of G protein-coupled receptor activity under normal physiologic circumstances.

Amino Acid Sequence↗
PubMed2001

Hmx2 homeobox gene control of murine vestibular morphogenesis.

Development of the vertebrate inner ear is characterized by a series of genetically programmed events involving induction of surface ectoderm, preliminary morphogenesis, specification and commitment of sensory, nonsensory and neuronal cells, as well as outgrowth and restructuring of the otocyst to form a complex labyrinth. Hmx2, a member of the Hmx homeobox gene family, is coexpressed with Hmx3 in the dorsolateral otic epithelium. Targeted disruption of Hmx2 in mice demonstrates the temporal and spatial involvement of Hmx2 in the embryonic transition of the dorsal portion (pars superior) of the otocyst to a fully developed vestibular system. In Hmx2 null embryos, a perturbation in cell fate determination in the lateral aspect of the otic epithelium results in reduced cell proliferation in epithelial cells, which includes the vestibular sensory patches and semicircular duct fusion plates, as well as in the adjacent mesenchyme. Consequently, enlargement and morphogenesis of the pars superior of the otocyst to form a complex labyrinth of cavities and ducts is blocked, as indicated by the lack of any distinguishable semicircular ducts, persistence of the primordial vestibular diverticula, significant loss in the three cristae and the macula utriculus, and a fused utriculosaccular chamber. The developmental regulators Bmp4, Dlx5 and Pax2 all play a critical role in inner ear ontogeny, and the expression of each of these genes is affected in the Hmx2 null otocyst suggesting a complex regulatory role for Hmx2 in this genetic cascade. Both Hmx2 and Hmx3 transcripts are coexpressed in the developing central nervous system including the neural tube and hypothalamus. A lack of defects in the CNS, coupled with the fact that not all of the Hmx2-positive regions in developing inner ear are impaired in the Hmx2 null mice, suggest that Hmx2 and Hmx3 have both unique and overlapping functions during embryogenesis.

Animals↗
PubMed2001

Free vertical moments and transverse forces in human walking and their role in relation to arm-swing.

We present force plate data on vertical free moments (force couples in the horizontal plane between the foot and the ground) and on transverse force during unloaded walking in different modes and at different speeds (including running) by adults of both sexes and by children, and examine loaded walking by adult males and one boy. Free moments in slow and normal-speed walking are characterised by a lateral peak in the accelerative phase of stance, but the peak during running, and in some cases of fast walking, occurs in the deceleration phase. Free moments are strongly affected by arm fixation in males, but less so in females. The pattern, but not the scale, of free moments is affected by loading position and side, but load magnitude has little effect if the loaded weight is treated as part of the body. Transverse force is more variable than sagittal force. In males, the transverse force curve shows a marked trough at mid-stance, whereas in females this trough is rarely seen. The transverse force of males also differs from that of females in response to arm fixation, showing a local medial inflection at three-quarters of the stance phase that is not present in females. Adults differ from children younger than 9 years in the presence of a very short, medially directed peak following heel-strike. Analysis of the effects of arm fixation and the timing of forces suggests strongly that arm-swing and free moments tend to reinforce each other in balancing trunk torques induced by the lower limbs. Both are of reduced importance in slow walking.

Adult↗
PubMed2001

A genome-based study of the Muslim Hui community and the Han population of Liaoning Province, PR China.

To investigate the proposed historical origins of the Hui, a Chinese Muslim minority resident in Liaoning Province, PR China, DNA samples obtained from 53 individuals were analyzed at ten autosomal and six Y-chromosome microsatellite loci. As reference sources, equivalent samples were investigated from the coresident Han majority population. Both the Hui and the Han exhibited appreciable genetic heterogeneity in terms of the size, number, and size range of alleles, suggestive of population substructure resulting from their particular cultural and historical backgrounds. The contrast in the patterns of autosomal and Y-chromosome diversity of the two communities was obvious. Analysis of molecular variance showed that only 4.6% of total autosomal molecular variance was due to differences between the Hui and Han. The comparable value for Y-chromosome haplotype distributions of 14.0% indicated that the Hui and Han of Liaoning have separate paternal genetic histories.

Alleles↗
PubMed2001

Signal transduction in electrically stimulated bone cells.

BACKGROUND: Electrical stimulation is used to treat nonunions and to augment spinal fusions. We studied the biochemical pathways that are activated in signal transduction when various types of electrical stimulation are applied to bone cells. METHODS: Cultured MC3T3-E1 bone cells were exposed to capacitive coupling, inductive coupling, or combined electromagnetic fields at appropriate field strengths for thirty minutes and for two, six, and twenty-four hours. The DNA content of each dish was determined. Other cultures of MC3T3-E1 bone cells were exposed to capacitive coupling, inductive coupling, or combined electromagnetic fields for two hours in the presence of various inhibitors of signal transduction, with or without electrical stimulation, and the DNA content of each dish was determined. RESULTS: All three signals produced a significant increase in DNA content per dish compared with that in the controls at all time-points (p < 0.05), but only exposure to capacitive coupling resulted in a significant, ever-increasing DNA production at each time-period beyond thirty minutes. The use of specific metabolic inhibitors indicated that, with capacitive coupling, signal transduction was by means of influx of Ca(2+) through voltage-gated calcium channels leading to an increase in cytosolic Ca(2+) (blocked by verapamil), cytoskeletal calmodulin (blocked by W-7), and prostaglandin E2 (blocked by indomethacin). With inductive coupling and combined electromagnetic fields, signal transduction was by means of intracellular release of Ca(2+) leading to an increase in cytosolic Ca(2+) (blocked by TMB-8) and an increase in activated cytoskeletal calmodulin (blocked by W-7). CONCLUSIONS: The initial events in signal transduction were found to be different when capacitive coupling was compared with inductive coupling and with combined electromagnetic fields; the initial event with capacitive coupling is Ca(2+) ion translocation through cell-membrane voltage-gated calcium channels, whereas the initial event with inductive coupling and with combined electromagnetic fields is the release of Ca(2+) from intracellular stores. The final pathway, however, is the same for all three signals-that is, there is an increase in cytosolic Ca(2+) and an increase in activated cytoskeletal calmodulin.

Animals↗