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Biomedical subjects

D Wang

Publications and source records attributed to D Wang.

At least 91 records · Page 5Linked to original sources

Pre- and postsynaptic GABA(B) receptors modulate rapid neurotransmission from suprachiasmatic nucleus to parvocellular hypothalamic paraventricular nucleus neurons.

The suprachiasmatic nucleus (SCN), the dominant circadian pacemaker in mammalian brain, sends axonal projections to the hypothalamic paraventricular nucleus (PVN), a composite of magno- and parvocellular neurons. This neural network likely offers SCN output neurons a means to entrain diurnal rhythmicity in various autonomic and neuroendocrine functions. Earlier investigations using patch-clamp recordings in slice preparations have suggested differential innervation by SCN efferents to magnocellular versus parvocellular PVN cells. In magnocellular PVN, cells respond to focal electrical stimulation in SCN with a GABA(A) receptor-mediated postsynaptic inhibition whose magnitude can be modulated by presynaptic GABA(B) receptors. By contrast, SCN-evoked responses in parvocellular PVN neurons typically involve both GABA(A)- and glutamate-receptor-mediated components. In the present patch-clamp study, 69/85 periventricular parvocellular PVN cells displayed SCN-evoked inhibitory and/or excitatory postsynaptic currents (IPSCs; EPSCs). In the presence of selective receptor antagonists, we sought evidence for their modulation by GABA acting at pre- and/or postsynaptic GABA(B) receptors. Cells responded to bath-applied baclofen (5-10 microM) with a tetrodotoxin-resistant membrane hyperpolarization associated with a reduction in input resistance and/or outward current, due to increase in a potassium conductance, blockable with 2-hydroxysaclofen (300 microM). At 1 microM where baclofen had no significant postsynaptic effect, evidence of activation of presynaptic GABA(B) receptors included reduction in SCN-evoked IPSCs and EPSCs with no change in their kinetics, and paired-pulse depression that was sensitive to both baclofen and saclofen. Baclofen also induced significant reductions in frequency but not amplitudes of miniature IPSCs and EPSCs. These observations suggest that levels of synaptically released GABA from the terminals of SCN output neurons can influence the relative contribution of pre- versus postsynaptic GABA(B) receptors in modulating both excitatory and inhibitory SCN innervation to parvocellular PVN neurons.

Animals↗

GLUT-1 deficiency without epilepsy--an exceptional case.

The GLUT-1 deficiency is a metabolic disorder caused by a defect in glucose transport across the blood-brain barrier as a result of a defect in the glucose-transport protein. Patients present with epileptic seizures, delayed development, ataxia and hypotonia, and in many cases acquired microcephaly. In most patients, treatment with a ketogenic diet proved to be successful in controlling the epilepsy. We report a 9-year-old boy with retardation and ataxia, but without epilepsy, caused by GLUT-1 deficiency, proven biochemically and by DNA analysis. Treatment with a medium-chain triglyceride ketogenic diet had a beneficial effect.

Ataxia↗

Caspase-9 is activated in a cytochrome c-independent manner early during TNFalpha-induced apoptosis in murine cells.

FL5.12 pro-B lymphoma cells utilize the mitochondrial pathway to apoptosis in response to tumor necrosis factor (TNF) receptor occupation, yet high levels of the Bcl-2 family antiapoptotic protein, Bcl-x(L), fail to protect these cells against TNF-receptor-activated death. Bcl-x(L) expression delays, but does not totally block, the release of mitochondrial cytochrome c (cyt c) in these cells in response to TNFalpha-induced apoptosis and caspase-9 is processed prior to mitochondrial cyt c release under these circumstances. Early processing of caspase-9 also occurred in Apaf-1 knockout murine fibroblasts in response to TNF-receptor occupation. A caspase-9-specific inhibitor was more effective in delaying the progression of apoptosis in the FL5.12 Bcl-x(L) cells than was an inhibitor specific to caspase-3. Furthermore, downregulation of caspase-9 levels by RNA interference resulted in partial protection of these cells against TNF-receptor-activated apoptosis, indicating that caspase-9 activation contributed to early amplification of the caspase cascade. Consistent with this, proteolytic processing of caspase-9 was observed prior to processing by caspase-3, suggesting that caspase-3 was not responsible for early caspase-9 activation. We show that murine caspase-9 is efficiently processed by active caspase-8 at SEPD, the motif at which caspase-9 autoprocesses following its recruitment to the apoptosome. Our results suggest that, in addition to processing procaspase-3 and the BH3 protein Bid, active caspase-8 can cleave and activate procaspase-9 in response to TNF receptor crosslinking in murine cells.

Amino Acid Sequence↗

Efficient and long-term intracardiac gene transfer in delta-sarcoglycan-deficiency hamster by adeno-associated virus-2 vectors.

Intracardiac gene transfer and gene therapy have been investigated with different vector systems. Here we used adeno-associated virus (AAV) vectors to deliver either a reporter gene or a therapeutic gene into the heart of golden Syrian hamsters. The method of gene delivery was direct infusion of the AAV2 vectors into the coronary artery ex vivo in a heterotopically transplanted heart. When an AAV2 vector carrying the Lac-Z gene driven by CMV promoter was delivered into the heart of healthy hamsters, effective gene transfer was achieved in up to 90% of the cardiomyocytes. Lac-Z gene expression persisted for more than 1 year without immune rejection or promoter shutoff. Furthermore, when an AAV2 vector carrying human delta-sarcoglycan gene was similarly delivered into the heart of Bio14.6 Syrian hamster, a congestive heart failure and limb girdle muscular dystrophy animal model, widespread therapeutic gene transfer was achieved in a majority of the cardiomyocytes. Efficient expression of the human delta-sarcoglycan gene in the dystrophic hamster hearts restored the entire sarcoglycan complex that was missing due to the primary deficiency of delta-sarcoglycan. Transgene expression persisted for 4 months (the duration of the study) without immune rejection or promoter shutoff. These results indicate that AAV is a promising vector system for cardiac gene therapy.

Animals↗

Mobility of the spine after spinal surgery in acute spinal cord injury.

STUDY DESIGN: Retrospective study of mobility of the spine. OBJECTIVES: To study the relation between mobility of the spine, operation and length of surgical stabilisation. SETTING: The National Spinal Injuries Centre, Stoke Mandeville Hospital, Aylesbury, UK. METHOD: Questionnaires were sent to 99 consecutive acute traumatic spinal cord-injured patients (UK residents) admitted in 1990-1994. All had acute spinal surgery. A total of 68 responded. Their replies, medical records and radiographs were reviewed. RESULTS: (1) In all, 63 patients had surgery in the cervical, thoracolumbar or lumbar spine; 11 of them had more than two functional spinal units (FSUs) stabilised, 10 of these 11 (91%) had less than satisfactory results in terms of metal failure, improper placement of the implant or functional restriction of spinal mobility (FROSM). A total of 35 had 1-2 FSUs stabilised. None of them had metal failure or improper placement of implant, but 14 (40%) had less than satisfactory result due to FROSM; 17 had laminectomy alone, four of these had FROSM. (2) Five patients had surgery in the thoracic spine. Three of these who had 5-7 FSUs stabilised had no FROSM. Two had laminectomy alone, one of whom had FROSM. CONCLUSION: (1) Long surgical stabilisation in the cervical, thoracolumbar and lumbar spines was likely to result in either metal failure or FROSM. (2) Long surgical stabilisation of the thoracic spine was not associated with either metal failure or FROSM. (3) A small proportion of patients had laminectomy alone. One of them who had multiple injuries had FROSM.

Adolescent↗

Disseminated trichosporonosis in China.

A 20-year-old female patient presented with erythematous plaques on the nose which were progressively spreading to the trunk and the extremities, sometimes with erosions and scars. The patient was misdiagnosed as having seborrhoeic dermatitis and subacute cutaneous lupus erythematosus. The histopathological biopsy revealed mycotic infectious granuloma. Samples taken from skin lesions and other locations grew Trichosporon asahii in cultures. The identification was confirmed by molecular biological methods. The patient was treated successfully with liposomal amphotericin B in combination with fluconazole orally.

Adult↗

The neointimal response to endovascular injury is increased in obese Zucker rats.

BACKGROUND: Restenosis after revascularization procedures is accelerated in persons with type 2 diabetes. AIM: The current study tested the hypothesis that the neointimal response to endovascular injury is enhanced in female obese Zucker (OZ) rats, a model of type 2 diabetes. METHODS: Animals were randomized to receive either a standard diet (SD) or a diabetogenic diet (DD) for 6 weeks. Four weeks later, balloon injury of the right common carotid artery was induced. All rats were euthanized 2 weeks after injury. Lean Zucker (LZ) rats served as controls. RESULTS: At the time of death, plasma glucose was elevated in OZ rats fed a SD (208 +/- 13 mg/dl) and a DD (288 +/- 21 mg/dl) compared to corresponding LZ rats (SD: 153 +/- 8; DD: 132 +/- 7 mg/dl). The ratio of high-density lipoprotein cholesterol (HDLc) to total cholesterol (Totc), an index of atherogenicity, was reduced in OZ rats on both diets (SD: 0.77 +/- 0.06; DD: 0.80 +/- 0.09) compared to LZ controls (SD: 1.11 +/- 0.02; DD: 1.20 +/- 0.05). Histomorphometric analysis of injured arteries showed that the intima to media (I : M) ratio was significantly increased in OZ (1.37 +/- 0.07) compared to LZ (0.79 +/- 0.08) rats. Elevations in plasma glucose and triglycerides (Tg) correlated positively and decreases in HDLc negatively with an increased I : M ratio. Administration of the DD did not further enhance the I : M ratio in LZ (0.87 +/- 0.06) or OZ (1.29 +/- 0.09) rats. CONCLUSIONS: These results suggest that neointima formation following endoluminal injury of the carotid artery is enhanced at an early stage in the development of diabetes mellitus.

Animals↗

Response of Schwann cells in the inferior alveolar nerve to distraction osteogenesis: an ultrastructural and immunohistochemical study.

The biological mechanisms of nerve adaptation to distraction osteogenesis have not yet been elucidated. This study observed response of Schwann cells in the inferior alveolar nerve (IAN) following mandibular lengthening by electron microscopy and immunohistochemistry of S-100 protein, a specific marker of Schwann cells. Unilateral mandibular distraction (10mm elongation) was performed in nine young adult goats. Three animals were sacrificed at 7, 14 and 28 days after completion of distraction, respectively. The distracted IAN specimens and control nerves (from the contralateral sides) were harvested and processed for histological, ultrastructural and immunohistochemical examinations. Wallerian degeneration was observed in the distracted IAN, and Signs of axonal regeneration, as well as many activated Schwann cells were seen in the lengthened nerves. The expression of S-100 protein increased significantly at early stage of distraction osteogenesis, but almost returned to the normal level at 28 days after distraction. This study suggests that Wallerian degeneration caused by mechanical stretching may stimulate Schwann cells to enter a proliferated and activated state. Schwann cells and S-100 protein appear to play crucial roles in axonal regeneration that contributes to nerve adaptation to gradual distraction. Therefore, the IAN injury caused by mandibular gradual distraction was not serious; it seems to recover totally through a complicated repair mechanism.

Adaptation, Biological↗

Albumin and fibrinogen adsorption on cibacron blue F3G-A immobilised onto PU-PHEMA (polyurethane-poly(hydroxyethylmethacrylate)) surfaces.

In the present work, it is intended to study the effect of Cibacron blue F3G-A (CB) immobilised onto PU-PHEMA (polyurethane-poly(hydroxyethylmethacrylate)) surfaces on protein adsorption and bacterial adhesion. CB immobilisation was carried out by covalent binding between its triazine ring and the hydroxyl groups of the polymer. Characterisation of the films was carried out by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FT-IR), contact angle measurements. X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). CB efficiency was evaluated using radiolabelled albumin and fibrinogen from pure solutions, mixtures of both and plasma. Bacterial adhesion tests before and after albumin pre-coating were also performed. The presence of CB increases albumin and fibrinogen adsorption to PU-PHEMA surfaces. The incorporation of CB onto the PU-PHEMA surface also increases bacterial adhesion. Although albumin pre-coating decreases bacterial adhesion onto PU (67% decrease) and PU-PHEMA-CB (80%), bacterial adhesion is always lower on PU and PU-PHEMA surfaces than on PU-PHEMA-CB. These results demonstrate that, in contrast to what has been described for CB bound to dextran, CB immobilisation on PU-PHEMA surfaces presents low selectivity to albumin and increased bacterial adhesion relatively to PU and PU-PHEMA surfaces.

Adsorption↗

Single nucleotide polymorphism discrimination assisted by improved base stacking hybridization using oligonucleotide microarrays.

Efficiencies of mismatch discrimination using size-varied capture probes were examined at various hybridization temperatures. The probes were 17, 15, 13, 11, 9, and 7 nucleotides long and contained single-base mismatches at their 3' ends. The optimal signal intensity and efficiency of base stacking hybridization on mismatch discrimination were observed for capture probes with a melting temperature (Tm) value of 36 degrees C, in the detection of DNA sequence variations at 40 degrees C. We employed asymmetric PCR to prepare single-stranded target DNA labeled with a fluorescent dye, and the PCR product was hybridized on the DNA microarray with no further purification. Our efforts have enhanced the sensitivity and simplified the procedures of base stacking hybridization on mismatch discrimination. As a model experiment, this improved technology was used to identify plasmid templates of human leukocyte antigen (HLA)-A alleles 2601, 2902, and 0206 on oligonucleotide microarrays. It is now possible to apply this simple, rapid, sensitive, and reliable base stacking hybridization technology to detect DNA sequence variations on microarrays in clinical diagnosis and other applications.

Alleles↗

Osteoblastic differentiation bioassay and its application to investigating the activity of fractions and compounds from Psoralea corylifolia L.

A cell differentiation bioassay measuring alkaline phosphatase activity was developed using osteoblast-like UMR 106 cell line as a model. The effect of fractions and compounds of Psoralea corylifolia L. extract on osteoblastic differentiation was investigated. The fractions or compounds were co-cultured with cells for 48 h, the cellular ALP activity was then measured. The crude ethanol extract of Psoralea corylifolia L. increased ALP activity by 39.5% at a concentration of 0.1 mg/ml, and the activity was concentrated in the ethyl acetate fraction, which produced a maximum ALP activity increase of 38.2%. A significant activity was observed for a flavonoid, corylin, providing 30.0% increment in ALP. These effects suggest that Psoralea corylifolia L. extract, its ethyl acetate fraction and corylin would stimulate bone formation.

Acetates↗

Immunohistochemical identification of components of the chemoattractant signal transduction pathway in vomeronasal bipolar neurons of garter snakes.

The chemosignal transduction pathway in the vomeronasal sensory epithelium of garter snakes involves activation of G-protein-coupled receptors and subsequent generation of second messengers leading to production of an electrical signal. Calcium imaging experiments demonstrate that ligand binding to the receptor leads to an increase in intracellular calcium and that the phosphatidylinositol-turnover pathway plays a major role in this Ca(2+) increase. Here, we demonstrate, using immunohistochemistry, that IP(3) receptors are largely distributed in dendritic regions of the epithelium, ryanodine receptors are confined to the somata region, and Na(+)/Ca(2+) exchanger protein is expressed throughout the vomeronasal (VN) sensory epithelium.

Animals↗

Carrier-mediated uptake and release of taurine from Bergmann glia in rat cerebellar slices.

Taurine uptake is essential for the maintenance of millimolar intracellular concentrations of taurine, which is released during ischaemia and is thought to be neuroprotective. To determine whether Bergmann glia express functional transporters that can mediate both taurine uptake and efflux, whole-cell patch-clamp recordings were obtained from these cells in rat cerebellar slices. Taurine-induced inward currents can be pharmacologically separated into GABA(A) receptor and taurine transporter currents. In the presence of GABA receptor blockers, residual taurine currents averaged -28 pA at -70 mV and were strictly inwardly rectifying between -70 and +50 mV. These residual currents were also abolished by external Na+ removal and diminished by reduction of external Cl-, consistent with transport currents. Taurine transport currents were reduced by a taurine transporter inhibitor, guanidinoethyl sulphonate (GES). Other classical inhibitors reduced taurine transport currents with an order of potency (hypotaurine > beta-alanine > GES > GABA) similar to that reported for cloned rat taurine transporters. Following intracellular taurine perfusion during the recording, a progressively developing outward current could be observed at -50 mV but not at -70 mV. Intracellular perfusion of taurine also decreased taurine-induced inward currents at both holding potentials. Outward currents induced by intracellular taurine increased in amplitude with depolarization, activated near -50 mV, and were affected by GES. For the first time, these results demonstrate that taurine activates both GABA(A) receptors and Na+/Cl--dependent taurine transporters in Bergmann glia in slices. In addition, our data show that taurine transporters can work in reverse and can probably mediate taurine efflux under ischaemic conditions.

Animals↗

Thiofunctional vanadium complexes.

The neutral tetradentate ligand 1,6-bis(2'-pyridyl)-2,5-dithiahexane (N(2)S(2)), containing two thioether functions, reacts with [VX(2)L(4)] (X = Br, L(4) = 2 tmeda (tmeda = Me(2)NCH(2)CH(2)NMe(2)); X = I, L = tetrahydrofuran (THF)) and [VX(3)(THF)(3)] (X = Br, I) to form the complexes [VX(2)(N(2)S(2))] (1) and [VX(2)(N(2)S(2))]X (2), respectively. [V(2)(mu-Cl)(3)(THF)(6)]I and N(2)S(2) yield the V(IV) complex [VOCl(N(2)S(2)]I (3). The pentadentate, dianionic ligand 2,6-bis(2'-mercaptophenylthio)dimethylpyridine, NS(2)S'(2)(2-), which contains two thioether (S) and two thiophenolate (S') functions, reacts with [VBr(3)(THF)(3)] to afford [VBr(NS(2)S'(2))] (4). The complex [VO(Cl)S'NS'] (5; H(2)S'NS' is the Schiff base formed between o-mercaptoaniline and o-mercaptobenzaldehyde) is obtained by redox interaction between [VCl(3)(THF)(3)] and 2,2'-dithiodibenzaldehyde in the presence of o-mercaptoaniline. The crystal and molecular structures have been obtained for 3. THF, 4. THF, and 5. n-C(5)H(12). The relevance of these compounds and their formation for the interaction between vanadium and thiofunctional biomolecules is addressed.

Journal Article↗

Cognitive impairment in Parkinson's disease revealed by event-related potential N270.

Disturbed cognitive function is a well-recognized feature of idiopathic Parkinson's disease (PD). The aim of this study was to find a susceptive index to reveal the minor cognitive impairment in PD patients. Thirty PD patients without clinical dementia and thirty-four age-matched normal controls performed a matching task while event-related potentials (ERPs) were recorded from their scalp. There were two kinds of stimulus pairs in this study: match condition, the second stimulus (S2) in a pair was identical to the first one (S1); conflict condition, S2 conflicted with S1 in the color attribute. Subjects were required to press a button in the match condition and another button in the conflict condition. A negative ERP component, N270, which was considered to reflect the conflict processing activity in human brain, was evoked by the S2 of the conflict condition. The patient group showed a delayed and smaller N270 than the control group. The prolongation of its peak latency was significant at P3 and P4 electrodes and the reduction of its mean amplitude was significant at P3 electrode. The amplitude of P300 elicited in the match condition was decreased in the patient group at P4 electrode but its latency did not differ from the control group. These results indicate that PD patients as a group showed cognitive decline even in the absence of clinical dementia. N270 is a sensitive index in revealing this minor cognitive impairment.

Adult↗

Atomic configuration in core structure of Lomer dislocation in Si0.76Ge0.24/Si.

The core structure of a Lomer dislocation in SiGe/Si system has been revealed at atomic level. This is attained by applying the image deconvolution technique in combination with dynamical diffraction effect correction to the high-resolution image taken with a 200 kV field-emission gun high-resolution electron microscope. The Lomer dislocation has a Hornstra-like core. The contrast of the image simulated on the basis of derived atomic configuration is in agreement with that of the experimental image.

Journal Article↗

Growth of human T cell acute lymphoblastic leukemia lymphoblasts in NOD/SCID mouse fetal thymus organ culture.

The in vitro proliferation of T cell acute lymphoblastic leukemia (T-ALL) cells in its entirety has not been well delineated because of a lack of an appropriate culture system that mimics the growth pattern in a living body. We applied a NOD/SCID mouse fetal thymus organ culture (FTOC) for leukemic cells from fresh (one case) and frozen (seven cases) bone marrow (BM) samples of children with T-ALL. Cell growth was observed in all seven samples in the culture, reaching a proliferational peak at 4 weeks, and it was calculated that the proliferation potential was 212-to 319-fold. The FTOC-derived T-ALL cells showed similarity to the original cells morphologically and immunophenotypically, still possessed clonalities and were able to regenerate overt leukemia in NOD/SCID mice. These FTOC-derived T-ALL cells differed from ordinary cell lines because they always need FTOC support. Thus, we established a new in vitro culture for T-ALL cells. A comparison of the original and FTOC-derived T-ALL cells revealed that the proportion of cells expressing IL-7R increased in all seven cases. Sorting and re-seeding of FTOC-derived IL-7R+ and IL-7R- cells into secondary FTOC resulted in a predominant generation of IL-7R+ cells from both fractions, while IL-7R- cells proliferated more potently than did IL-7R+ cells, suggesting that a pathway for the conversion of IL-7R- to IL-7R+ exists during the proliferation of T-ALL lymphoblasts. Addition of exogenous IL-7 or neutralization with anti-IL-7 antibody did not influence the growth pattern of T-ALL cells in FTOC. The current study provides a unique assay system for the exploration of the hierarchy within human T-lymphoid leukemic cells, and should facilitate the establishment of novel therapeutic modalities.

Animals↗

Differences in mandibular distraction osteogenesis after corticotomy and osteotomy.

Corticotomy or osteotomy was performed on opposing sides of the mandibles in 18 goats. A custom-made distractor was used to lengthen the mandible at a rate of 1 mm/day for 10 days (total 10 mm elongation). Six goats were sacrificed respectively at 2, 4 and 8 weeks after completion of distraction. The distracted calluses were harvested and processed for radiographic, histologic, and scanning electron microscopic evaluation as well as Ca/P ratio analysis. The regenerate bone in the corticotomy side showed more bone formation and earlier mineralization than in the osteotomy side. The results of this study suggest that preservation of intramedullary vessels is beneficial to bone regeneration following mandibular osteodistraction, and that performing corticotomy may be a simple but effective way to promote the maturity of the distracted callus and shorten the time for fixation.

Animals↗