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Biomedical subjects

C Wang

Publications and source records attributed to C Wang.

At least 811 records · Page 45Linked to original sources

Binocular interactions and disparity coding in area 21a of cat extrastriate visual cortex.

We have examined, using both qualitative and quantitative techniques, binocular interactions of extracellularly recorded single neurons in the extrastriate cortical area 21a of anaesthetized and paralysed cats. Consistent with previous reports we have found that: (a) all area 21a neurons were orientation-selective, with about 65% of them preferring orientations within 30 degrees of the vertical; and (b) over 75% of area 21a cells could be activated through either eye. Furthermore, a significant minority (4 cells; about 10%) of a subpopulation of 39 neurons in which binocular interactions were examined quantitatively, were "obligatory binocular neurons", that is, they responded very weakly, if at all, to the monocular stimuli presented through either eye but responded vigorously to simultaneous stimulation through both eyes. Almost 70% (27/39) of neurons tested quantitatively for binocular interaction have shown significant modulation (over 50%) of their peak responses in relation to binocular positional retinal disparities. The majority of neurons sensitive to binocular positional disparities resembled either "tuned excitatory" (22 cells; 56.5% of the sample) or "tuned inhibitory" (2 cells; 5% of our sample) cells. In particular, they gave, respectively, maximal or minimal responses to optimally oriented, moving photic stimuli when the receptive fields plotted through each eye completely or partially overlapped. Although neurons recorded in area 21a have relatively large receptive fields (mean width 3.3 +/- 1.1 degrees; range 2.0-5.6 degrees), the mean width of the disparity tuning curve (2.8 +/- 1.0 degrees; range 1.3-4.8 degrees) for our sample of area 21a neurons was similar to those of neurons with significantly smaller receptive fields, recorded in areas 17 and 18 of cat's primary visual cortex. We conclude that area 21a of the cat, like areas 17 and 18 of primary visual cortex, is likely to play an important role in binocular depth discrimination and might constitute a "higher order" area for stereoscopic binocular vision.

Animals↗

Treatment of lumbar disc herniation in the second decade of life.

Lumbar disc herniation is rare in patients under the age of 20 years. In the department of orthopaedic surgery of the University Hospital of Frankfurt, 33 patients below the age of 20 with lumbar disc herniation were treated over a period of 10 years. Eighteen were managed conservatively and 15 surgically. The purpose of this study is to report on the long-term outcome of these patients and to compare the results of conservative and surgical treatment. We analysed information obtained from the medical records, and for the long-term follow-up we prepared a questionnaire. The questionnaire was composed of general questions about the patients' lifestyle and their ability to return to a normal life and activity after treatment, together with a request for them to score their pain level and remaining symptoms. We found that the longest duration of symptoms before diagnosis was 72 months, with a mean duration of 11.1 months. Low back pain and monoradicular sciatica were the main complaints, but findings of neurological deficits were rare. Lasegue's sign and tight hamstrings seemed to be strong diagnostic signs in this age group. On the day of discharge, 94% of patients reported excellent or good results. The outcomes after a mean follow-up period of 5.4 years were similar in both treatment groups. Almost all patients were able to attain a normal activity level and few reported restrictions on their daily life. Only 14% complained of permanent pain and 7% reported poor results regarding their activity capabilities. In conclusion, we believe that in all cases of lumbar disc herniation in the second decade of life, conservative treatment should be pursued as a mainstay of treatment. Only after a certain time, if conservative treatment is ineffective, should surgical treatment be considered.

Adolescent↗

Distribution of hyaluronan in articular cartilage as probed by a biotinylated binding region of aggrecan.

The proportion of total tissue hyaluronan involved in interactions with aggrecan and link protein was estimated from extracts of canine knee articular cartilages using a biotinylated hyaluronan binding region-link protein complex (bHABC) of proteoglycan aggregate as a probe in an ELISA-like assay. Microscopic sections were stained with bHABC to reveal free hyaluronan in various sites and zones of the cartilages. Articular cartilage, cut into 20 microns-thick sections, was extracted with 4 M guanidinium chloride (GuCl). Aliquots of the extract (after removing GuCl) were assayed for hyaluronan, before and after papain digestion. The GuCl extraction residues were analyzed after solubilization by papain. It was found that 47-51% of total hyaluronan remained in the GuCl extraction residue, in contrast to the 8-15% of total proteoglycans. Analysis of the extract revealed that 24-50% of its hyaluronan was directly detectable with the probe, while 50-76% became available only after protease digestion. The extracellular matrix in cartilage sections was stained with the bHABC probe only in the superficial zone and the periphery of the articular surfaces, both sites known to have a relatively low proteoglycan concentration. Trypsin pretreatment of the sections enhanced the staining of the intermediate and deep zones, presumably by removing the steric obstruction caused by the chondroitin sulfate binding region of aggrecans. Enhanced matrix staining in these zones was also obtained by a limited digestion with chondroitinase ABC. The results indicate that a part of cartilage hyaluronan is free from endogenous binding proteins, such as aggrecan and link protein, but that the chondroitin sulfate-rich region of aggrecan inhibits its probing in intact tissue sections. Therefore, hyaluronan staining was more intense in cartilage areas with lower aggrecan content. A large proportion of hyaluronan resists GuCl extraction, even from 20-micrograms-thick tissue sections.

Aggrecans↗

An ECG storage and retrieval system embedded in client server HIS utilizing object-oriented DB.

In the University of Tokyo Hospital, the improved client server HIS has been applied to clinical practice and physicians can order prescription, laboratory examination, ECG examination and radiographic examination, etc. directly by themselves and read results of these examinations, except medical signal waves, schema and image, on UNIX workstations. Recently, we designed and developed an ECG storage and retrieval system embedded in the client server HIS utilizing object-oriented database to take the first step in dealing with digitized signal, schema and image data and show waves, graphics, and images directly to physicians by the client server HIS. The system was developed based on object-oriented analysis and design, and implemented with object-oriented database management system (OODMS) and C++ programming language. In this paper, we describe the ECG data model, functions of the storage and retrieval system, features of user interface and the result of its implementation in the HIS.

Database Management Systems↗

Effect of chloride channel blockers on the cardiac CFTR chloride and L-type calcium currents.

OBJECTIVES: The aim of this study was to determine the effects of Cl- channel blockers on the cardiac cystic fibrosis transmembrane conductance regulator (CFTR) Cl- current (ICl) and the protein kinase A-regulated L-type calcium current (PKA-ICa). METHODS: Whole-cell ICl and ICa were recorded from isolated guinea pig ventricular myocytes using the patch clamp technique during stimulation of PKA by forskolin (1 or 2 microM). RESULTS: The inhibitory effects of clofibric acid, p-chlorophenoxy propionic acid, gemfibrozil, diphenylamine-2-carboxylate (DPC), anthracene-9-carboxylate, 4,4'dinitrostilbene-2,2'-disulfonic acid and indanyloxyacetic acid 94 were examined on the two currents. Clofibric acid (1 mM), p-chlorophenoxy propionic acid (1 mM) and gemfibrozil (250 microM) produced an approximate 50% decrease in ICl, but had no effect on the PKA-ICa. Surprisingly, application of DPC (500 microM and 1 mM) and anthracene-9-carboxylate (500 microM) strongly reduced both currents. However, inhibition of the Ca2+ and Cl- channels by DPC could be differentiated in two important ways. First, increasing the pH of the external solution from 7.4 to 10.0 prevented the block of ICl by DPC, but did not attenuate the reduction in the PKA-ICa. Second, DPC inhibited the PKA-ICa in mouse atrial myocytes which lacked ICl. Neither 4,4'dinitrostilbene-2,2'-disulfonic acid (100 microM) nor indanyloxyacetic acid 94 (50 microM) caused any change in either of the guinea pig ventricular currents. CONCLUSIONS: Drugs such as DPC and anthracene-9-carboxylate which block the cardiac CFTR Cl- channel also inhibit the regulation of the L-type ICa. During beta-adrenergic stimulation, changes produced by these drugs on the cardiac action potential duration will be attributable to inhibition of both the Cl- and Ca2+ currents. Analogues of clofibric acid may serve as selective blockers of the CFTR Cl- channel that can be used to determine the physiological function of ICl in cardiac excitation.

Animals↗

Effect of 5,7-dihydroxytryptamine on audiogenic seizures in genetically epilepsy-prone rats.

To further assess the role of 5-HT in the modulation of audiogenic seizures (AGS) in the Genetically Epilepsy-Prone Rat (GEPR), changes in AGS severity after widespread chronic depletion of brain 5-HT by intracerebroventricular administration of 5,7-dihydroxytryptamine (5,7-DHT) were examined in moderate seizure GEPRs (GEPR-3s). Following treatment with 5,7-DHT (150 micrograms/30 microliters), a significant increase in seizure severity was observed at 2, 3 and 4 weeks as compared to vehicle-injected controls. The increase in seizure severity was evidenced by a significant increase in the incidence of tonic convulsions in 5,7-DHT treated animals (53% in treated animals compared to 0% in vehicle treated controls) over the testing period. Interestingly, the latency to wild running was increased in 5,7-DHT treated GEPRs, suggesting that depletion of brain 5-HT may slow initiation of AGS. Neurochemical analysis revealed marked depletion of 5-HT in the cortex (-96%), hippocampus (-94%), thalamus (-80%), hypothalamus (-62%), midbrain (-51%) and pons-medulla (-52%) in animals that received 5,7-DHT. However, no significant reductions in brain norepinephrine content were observed in any of the regions assayed due to the pretreatment of all animals with protriptyline. The present findings lend further support for an inhibitory action of brain 5-HT on audiogenic seizures in GEPRs.

5,7-Dihydroxytryptamine↗

Chinese village women as visual anthropologists: a participatory approach to reaching policymakers.

In developing countries, rural women are often neither seen nor heard, despite their extraordinary contribution to the labor force. Photo novella is an innovative methodology that puts cameras in the hands of rural women and other constituents who seldom have access to those who make decisions over their lives. As an educational tool, the practice of photo novella has three main goals: (1) to empower rural women to record and reflect their lives, especially health needs, from their own point of view; (2) to increase their collective knowledge about women's health status; and (3) to inform policymakers and the broader society about health and community issues that are of greatest concern to rural women. In this paper we analyze the third goal: the contributions and limitations of photo novella as a tool for informing policymakers. We conceptualize first the theoretical and practical underpinnings of photo novella. After tracing the relationships among empowerment education, feminist theory, documentary photography and policy, we describe photo novella within the broader context of the Ford Foundation-supported Yunnan Women's Health and Development Program and explain its application for influencing policy based on our experience carrying out photo novella in China.

Adolescent↗

Comparative study of the effect of 21-aminosteroid and alpha-tocopherol on models of acute oxidative renal injury.

21-Aminosteroids have incited a great deal of interest owing to its ability to inhibit lipid peroxidation and prevent organ damage. The main mechanism by which 21-aminosteroids inhibit lipid peroxidation is similar to the naturally occurring chain-breaking antioxidant alpha-tocopherols. Therefore, to determine whether 21-aminosteroids offer any advantage over alpha-tocopherol, we compared their effects on an in vivo and in vitro models of renal injury. 21-Aminosteroid (U-74006 F) at 3 mg/kg or alpha-tocopherol succinate at 10 mg/kg was administered intravenously once before bilateral renal ischemia and again before reperfusion. Acute administration 21-aminosteroid but not alpha-tocopherol, was attended by suppression of ischemia reperfusion-induced renal lipid peroxidation and injury. However, 4 weeks of dietary enrichment of rats with alpha-tocopherol (1000 IU/kg) was effective in suppressing these ischemia reperfusion-induced changes. In cell culture system, concurrent presence of 21-aminosteroid but not alpha-tocopherol abrogated H2O2-induced renal epithelial lipid peroxidation and injury. However, alpha-tocopherol was completely effective when cells were incubated with it for 14 h. Further, only the cells incubated with vitamin E for 14 h-but not for 1 or 3 h-had a significant increase in vitamin E content, which suggests that a delay in prompt cellular up take of vitamin E may explain its lack of acute effects. Thus, unlike alpha-tocopherol, 21-aminosteroid appears readily and completely available for its chain-breaking antioxidant activity both in vitro and in vivo. 21-Aminosteroids may, therefore, offer a therapeutic advantage over alpha-tocopherols in acute injury settings.

Animals↗

Age dependence of NMDA receptor involvement in epileptiform activity in rat hippocampal slices.

The pattern of epileptiform activity recorded from a number of in vitro seizure models is age dependent: ictal discharges are observed in immature brain slices while interictal bursts are seen in adult brain slices. This study evaluated the involvement of the N-methyl-D-aspartate (NMDA) receptor in the age-dependency of epileptiform activity recorded in area CA1 of hippocampal slices in Mg(2+)-free medium. Incubation in Mg(2+)-free medium induced ictal activity in 84% of hippocampal slices from immature rats (postnatal 10-15 days). In contrast, adult slices responded with interictal bursting, while ictal activity was rare (9%). Bath application of the NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid (DL-APV, 20 microM) converted ictal activity to interictal activity in the hippocampal slices from immature rats. In adult slices, bath application of NMDA (10-20 microM) in Mg(2+)-free medium induced ictal-like discharges. Perfusion with NMDA (20 microM) in a medium containing 1.5 mM Mg2+ induced ictal activity in immature slices while it evoked only interictal bursts in adult slices. These results suggest that differences in NMDA receptor function may be involved in the age-dependency of epileptiform activity induced by Mg(2+)-free medium. Enhanced NMDA receptor-mediated activity may partially underlie increased seizure susceptibility in the immature brain.

Age Factors↗

Areas PMLS and 21a of cat visual cortex are not only functionally but also hodologically distinct.

In several cats, paired visuotopically matched injections of retrogradely transported fluorescent dyes, diamidino yellow (DY) and fast blue (FB), were made into two visuotopically organized, functionally distinct extrastriate cortical areas, the posteromedial lateral suprasylvian area (PMLS area) and area 21a respectively. After an appropriate survival time, the numbers of thalamic, claustral and cortical cells which were single-labelled with each dye as well as the numbers of cells in these structures labelled with both dyes (double-labelled cells) were assessed. The clear majorities of thalamic cells projecting to PMLS area (DY labelled cells) and to area 21a (FB labelled cells) were located in the ipsilateral lateral posterior-pulvinar complex with smaller proportions located in the laminae C and the medial intralaminar nucleus of the ipsilateral dorsal lateral geniculate nucleus and several nuclei of the rostral intralaminar thalamic group. Despite the fact that DY labelled (PMLS-projecting) and FB labelled (area 21 a-projecting) cells in all thalamic nuclei were well intermingled, only 1-5% of retrogradely labelled thalamic cells projected to both areas (cells double-labelled with both dyes). Small proportions of retrogradely labelled cells were located in the ipsilateral and to a lesser extent the contralateral dorsocaudal claustra. The proportions of claustral neurons retrogradely labelled with both dyes varied from 4 to 9%. Over half of the cortical neurons labelled retrogradely from area 21a or PMLS area were located in the supragranular layers of the ipsilateral area 17, with smaller proportions located in the supragranular layers of the ipsilateral areas 18 and 19 and even smaller proportions located in mainly but not exclusively, the infragranular layers of the ipsilateral areas 21b and 20a. Again despite strong spatial intermingling of neurons labelled with DY and these labelled with FB, the proportions of associational cortical neurons double-labelled with both dyes were small (2 to 5.5%). Finally, small proportions of neurons retrogradely labelled with DY or FB were located, mainly but not exclusively, in the supragranular layers of the contralateral areas 17, 18, 19 and 21a. Again, the proportions of the double-labelled neurons in the contralateral cortices were small (1-4.5%). Thus, the present study indicates that despite the fact that the diencephalic and telencephalic inputs to the visuotopically corresponding parts of area 21a and PMLS area originate from the same nuclei, areas and layers, the two areas receive their afferents from the largely separate populations of neurons.

Animals↗

Evaluation of normal and abnormal hyoid bone movement during swallowing by use of ultrasound duplex-Doppler imaging.

We developed a new method to analyze normal and abnormal movements of the hyoid muscular region as an indicator of hyoid bone motion during swallowing using ultrasound duplex-Doppler imaging. Hyoid bone motion can be monitored by studying the Doppler shift spectra and B-mode images produced by ultrasound duplex imaging of the hyoid region muscular attachments. We can accurately determine swallowing duration and trajectory of hyoid bone movement. This procedure can assist in discriminating between normal and abnormal movements of the hyoid bone and the surrounding muscles during swallowing. This method appears to be a highly consistent measure. We suggest that Doppler spectrum analysis can be used for defining hyoid position and displaying accurate movement, which may be useful in the diagnosis of swallowing disorders.

Adult↗

PSA-NCAM is required for activity-induced synaptic plasticity.

Hippocampal organotypic slice cultures maintained 10-20 days in vitro express a high level of the polysialylated embryonic form of neural cell adhesion molecule (NCAM) (PSA-NCAM). Treatment of the cultures with endoneuraminidase-N selectively removed polysialic acid (PSA) from NCAM and completely prevented induction of long-term potentiation (LTP) and long-term depression (LTD) without affecting cellular or synaptic parameters. Similarly, slices prepared from transgenic mice lacking the NCAM gene exhibited a decaying LTP. No inhibition of N-methyl-D-aspartic acid receptor-dependent synaptic responses was detected. Washout of the enzyme resulted in reexpression of PSA immunoreactivity which correlated with a complete recovery of LTP and LTD. This reexpression was blocked by TTX and low calcium and enhanced by bicuculline. Taken together, these results indicate that neuronal activity regulates the expression of PSA-NCAM at the synapse and that this expression is required for the induction of synaptic plasticity.

Animals↗

Hypoxia-induced hyperexcitability in vivo and in vitro in the immature hippocampus.

Hypoxia is the most common cause of neonatal seizures and encephalopathy. We have previously developed an in vivo experimental model of perinatal hypoxia which exhibits age-dependent acute and chronic epileptogenic effects. Between postnatal day (P) 10-12, the rat exhibits acute seizure activity during global hypoxia, while no seizures are induced at earlier (P5) or older (P60) ages. Rats exposed to hypoxia between P10-12 have reduced seizure thresholds to chemical convulsants in adulthood. The nonNMDA antagonists NBQX appears to suppress both the acute and long term epileptogenic effects of hypoxia. The age-dependency of the hyperexcitable response to hypoxia in vivo can be reproduced in vitro using hippocampal slices. In Mg(2+)-free media, hypoxia induced ictal discharges within 60 s of onset in 79% of slices from normal P10 rat pups compared to 11% of adult slices (p < 0.001). Model systems such as that described here allow for correlation of in vitro and in vivo electrophysiology and should provide data regarding the pharmacological and physiological characteristics of hypoxia-induced seizure activity in the immature brain which could ultimately be applied to therapeutic strategies.

Age Factors↗

Lipid peroxidation contributes to hydrogen peroxide induced cytotoxicity in renal epithelial cells.

We have examined the role of lipid peroxidation in the cytotoxicity of H2O2 in OK cells containing markedly differing amounts of cell membrane polyunsaturated fatty acids (PUFA). In OK cells grown in a serum free medium, PUFA were undetectable. The membranes of these cells contained predominantly oleic, stearic and palmitic acids. When cultured in medium containing 10% calf serum, OK cells contained measurable amounts of PUFA [linoleic (5 +/- 1%) and arachidonic acids (8 +/- 1%)]. When the serum containing medium was supplemented with 60 mM linoleic acid, the membrane content of both linoleic (21 +/- 1%) as well as arachidonic acid (15 +/- 1%) as substantially increased. The severity of injury induced by H2O2 in OK cells was substantially altered by the PUFA content of the cell membrane. Exposure of OK cells to 1.25 mM H2O2 for one hour resulted in more cell death (determined by a trypan blue assay) in cells grown in serum supplemented with linoleic acid with "normal" PUFA content (90 +/- 2%) than in cells with "reduced" levels of PUFA grown in unsupplemented calf serum (81 +/- 3%). Cells gown in defined, serum free medium with undetectable levels of PUFA suffered the least H2O2-induced lethal cell injury (47 +/- 8%). Comparable differences in the cytotoxicity of H2O2 among cells with differing PUFA content were found using a clonogenic assay of cell viability. Malondialdehyde (MDA) accumulation induced by 1.25 mM H2O2 was greater in cells with "normal" PUFA content (702 +/- 103 pM/microgram cell DNA/hr) than in cells with "reduced" PUFA (328 +/- 112 pM/100 microgram DNA/hr) and was undetectable in cells grown in defined, serum free medium. In summary, the content of PUFA of cells in culture is profoundly influenced by culture conditions. Our data provide novel and direct evidence that peroxidation of cell membranes contributes directly to the severity of cell injury and death induced by H2O2.

Animals↗

Expression monitoring by hybridization to high-density oligonucleotide arrays.

The human genome encodes approximately 100,000 different genes, and at least partial sequence information for nearly all will be available soon. Sequence information alone, however, is insufficient for a full understanding of gene function, expression, regulation, and splice-site variation. Because cellular processes are governed by the repertoire of expressed genes, and the levels and timing of expression, it is important to have experimental tools for the direct monitoring of large numbers of mRNAs in parallel. We have developed an approach that is based on hybridization to small, high-density arrays containing tens of thousands of synthetic oligonucleotides. The arrays are designed based on sequence information alone and are synthesized in situ using a combination of photolithography and oligonucleotide chemistry. RNAs present at a frequency of 1:300,000 are unambiguously detected, and detection is quantitative over more than three orders of magnitude. This approach provides a way to use directly the growing body of sequence information for highly parallel experimental investigations. Because of the combinatorial nature of the chemistry and the ability to synthesize small arrays containing hundreds of thousands of specifically chosen oligonucleotides, the method is readily scalable to the simultaneous monitoring of tens of thousands of genes.

Animals↗

Multicopy single-stranded DNA of Escherichia coli enhances mutation and recombination frequencies by titrating MutS protein.

Multicopy single-stranded DNA (msDNA) molecules consist of single-stranded DNA covalently linked to RNA. In Escherichia coli, such molecules are encoded by genetic elements called retrons. The DNA moieties of msDNAs have characteristic stem-loop structures, and most of these structures contain mismatched base pairs. Previously, we showed that retrons encoding msDNAs with mismatched base pairs are mutagenic when present in multicopy plasmids. In this study we show that such msDNAs, in a similar manner to genetic defects in mismatch repair, increase the frequency of interspecies recombination in matings between Salmonella typhimurium and E. coli. To demonstrate interference with mismatch repair by msDNA, we show that the addition of a plasmid containing the gene for MutS protein suppresses the mutagenic and recombinogenic effects of msDNAs. We also show that in mutS mutants, msDNA does not increase the frequency of either mutations or interspecies recombination. We conclude from these findings that the mutagenic and recombinogenic effects of msDNAs are due to titrating out MutS protein.

Adenosine Triphosphatases↗

Functional N-methyl-D-aspartate receptors in O-2A glial precursor cells: a critical role in regulating polysialic acid-neural cell adhesion molecule expression and cell migration.

The capacity for long-distance migration of the oligodendrocyte precursor cell, oligodendrocyte-type 2 astrocyte (O-2A), is essential for myelin formation. To study the molecular mechanisms that control this process, we used an in vitro migration assay that uses neurohypophysial explants. We provide evidence that O-2A cells in these preparations express functional N-methyl-D-aspartate (NMDA) receptors, most likely as homomeric complexes of the NR1 subunit. We show that NMDA evokes an increase in cytosolic Ca2+ that can be blocked by the NMDA receptor antagonist AP-5 and by Mg2+. Blocking the activity of these receptors dramatically diminished O-2A cell migration from explants. We also show that NMDA receptor activity is necessary for the expression by O-2A cells of the highly sialylated polysialic acid-neural cell adhesion molecule (PSA-NCAM) that is required for their migration. Thus, glutamate or glutamate receptor ligands may regulate O-2A cell migration by modulating expression of PSA-NCAM. These studies demonstrate how interactions between ionotropic receptors, intracellular signaling, and cell adhesion molecule expression influence cell surface properties, which in turn are critical determinants of cell migration.

Calcium↗