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Biomedical subjects

S Zhang

Publications and source records attributed to S Zhang.

At least 271 records · Page 15Linked to original sources

[Effects of acute infrasound exposure on vestibular and auditory functions and the ultrastructural changes of inner ear in the guinea pig].

OBJECTIVE: To define the effects of acute infrasound exposure on vestibular and auditory functions and the ultrastructural changes of inner ear in guinea pigs. METHODS: The animals involved in the study were exposed to 8 Hz infrasound at 135dB SPL for 90 minutes in a reverberant chamber. The sinusoidal pendular test (SPT), auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) were respectively detected pre-exposure and at 0(within 2 hrs), 2 and 5 day after exposure. The ultrastructures of the inner ear were observed by scanning electron microscopy. RESULTS: The slow-phase velocity and the frequency of the vestibular nystagmus elicited by sinusoidal pendular test (SPT) declined slightly following infrasound exposure, but the changes were not significant (P > 0.05). No differences in the ABR thresholds, the latencies and the interval peak latencies of I, III, V waves were found between the normal and the experimental groups, and among experimental groups. The amplitudes of DPOAE at any frequency declined remarkably in all experimental groups. The ultrastructures of the inner ear were damaged to different extent. CONCLUSION: Infrasound could transiently depress the excitability of the vestibular end-organs, decrease the function of OHC in the organ of Corti and cause damage to the inner ear of guinea pigs.

Animals↗

[Clinicopathologic analysis of rhinoscleroma].

OBJECTIVE: To investigate the clinicopathologic characteristics and reason of tissue injury caused by klebsiella rhinoscleromatis(KR) infection. METHODS: Twenty-four cases of rhinoscleromas in the nasal and pharyngeal region in this hospital from March 1983 to March 1998 were studied retrospectively. Warthin-Starry (W-S) stain was used in all cases and CD43, CD20, CD68, Lysozyme mark were observed in eleven specimens by ABC immunochemical method. Two cases were studied further with transmission electron microscopy. RESULTS: A great number of KR were found in Mikulicz cells and were confirmed further in the phagosomes in cytoplasm of Mikulicz cells, where a small number of endoplasmic reticulums and lysozymes was squeezed to the side of cells. A few of T-lymphocytes was found within the granuloma. CONCLUSION: Cellular immunity function of the patient with rhinoscleroma was depressed and the response to immunization of host which regards to KR was the major cause of tissue injury.

Adolescent↗

[A comparative observation preoperatively and postoperatively of nasal mucosa in chronic sinusitis treated with endoscopic sinus surgery].

OBJECTIVES: To study morphologic and functional mucosal changes both preoperatively and postoperatively in chronic sinusitis (CS) treated with endoscopic sinus surgery (ESS). METHODS: 1. Saccharin test and light microscopic examination of nasal mucosa were taken preoperatively and postoperatively in 32 cases with CS and in 28 normal subjects as control. 2. Scanning and transmission electron microscopy were performed to exam preoperatively and postoperatively the nasal mucosa in 10 cases with CS and in 2 normal cases as control. RESULTS: 1. The preoperative saccharin test time (STT) in patients with CS was significantly longer than that in the controls (P < 0.001), and the postoperative STT became significantly shorter than that in preoperative one(P < 0.001). 2. The pathological changes of nasal mucosa, such as infiltration in inflammatory cells, edema, polypoid formations and pathologic glands were observed preoperatively. The infiltration in inflammatory cells, edema and polypoid formations were significantly released (P < 0.01) at four months after operation, and there was no significant difference comparing with the controls (P > 0.05). However, the pathologic glands were not reduced even after four months postoperatively. 3. The examination of electron microscopy demonstrated that the ultrastructure of nasal mucosa was impaired preoperatively and almost completely recovered at four months postoperatively. CONCLUSIONS: The normal structure and clearance function of nasal mucosa in patients with CS was impaired preoperatively, and the impaired structure and mucociliary clearing function of nasal mucosa were greatly improved after ESS and almost completely recovered at four months postoperatively. The pathologic glands and secretive function of nasal mucosa may need longer period for recovering.

Adolescent↗

Preliminary studies on associations of IDDM3, IDDM4, IDDM5 and IDDM8 with IDDM in Chengdu population.

OBJECTIVE: To study the associations of IDDM3, IDDM4, IDDM5 and IDDM8 with insulin-dependent diabetes mellitus (IDDM). METHODS: The polymorphisms of short tandem repeat (STR) loci D15S657, D11S1369, D6S2420 and D6S503, linked to IDDM3, IDDM4, IDDM5 and IDDM8 respectively, were studied by polymerase chain reaction and polyacrylamide gel electrophoresis (PCR-PAGE) followed by direct sequencing of PCR products in 105 normal Chinese Han nationality subjects and 48 patients with IDDM. RESULTS: The allele frequencies of allele A5 at D15S657 locus, allele A5 at D11S1369 locus and allele A4 at D6S2420 locus were increased significantly in patients with IDDM compared to those in the control group. No difference in the allele frequencies at D6S503 locus was observed between IDDM and control group. CONCLUSION: IDDM3, IDDM4, IDDM5 but not IDDM8 may be associated with IDDM in Chinese Han nationality population.

Adolescent↗

[Determination of trace cadmium in human hair, fingernail and toenail for ten years by flame atomic absorption spectrometry].

The human hair, fingernail and toenail were collected from one person quarterly for about ten years, respectively thirty-three, forty-one and thirty-nine shares. The contents of traces cadmium in hair, fingernail and toenail have been determined by flame atomic absorption spectrometry, and the results were satisfactory. From a changing curve in human hair, fingernail and toenail cadmium by age, we found that the range of cadmium contents in hair was 0.0100-0.4100 microgram.g-1, in fingernail 0.0295-0.5314 microgram.g-1, in tene-nail 0.0899-1.274 micrograms.g-1, respectively. In the changing curve there is a nonlinear characteristic.

Cadmium↗

Definition of the p53 functional domains necessary for inducing apoptosis.

The p53 protein contains several functional domains necessary for inducing cell cycle arrest and apoptosis. The C-terminal basic domain within residues 364-393 and the proline-rich domain within residues 64-91 are required for apoptotic activity. In addition, activation domain 2 within residues 43-63 is necessary for apoptotic activity when the N-terminal activation domain 1 within residues 1-42 is deleted (DeltaAD1) or mutated (AD1(-)). Here we have discovered that an activation domain 2 mutation at residues 53-54 (AD2(-)) abrogates the apoptotic activity but has no significant effect on cell cycle arrest. We have also found that p53-(DeltaAD2), which lacks activation domain 2, is inert in inducing apoptosis. p53-(AD2(-)DeltaBD), which is defective in activation domain 2 and lacks the C-terminal basic domain, p53-(DeltaAD2DeltaBD), which lacks both activation domain 2 and the C-terminal basic domain, and p53-(DeltaPRDDeltaBD), which lacks both the proline-rich domain and the C-terminal basic domain, are also inert in inducing apoptosis. All four mutants are still capable of inducing cell cycle arrest, albeit to a lesser extent than wild-type p53. Interestingly, we have found that deletion of the N-terminal activation domain 1 alleviates the requirement of the C-terminal basic domain for apoptotic activity. Thus, we have generated a small but potent p53-(DeltaAD1DeltaBD) molecule. Furthermore, we have determined that at least two of the three domains (activation domain 1, activation domain 2, and the proline-rich domain), are required for inducing cell cycle arrest. Taken together, our results suggest that activation domain 2 and the proline-rich domain form an activation domain for inducing pro-apoptotic genes or inhibiting anti-apoptotic genes. The C-terminal basic domain is required for maintaining this activation domain competent for transactivation or transrepression.

Apoptosis↗

Stat4 regulates multiple components of IFN-gamma-inducing signaling pathways.

Stat4 is activated in response to IL-12. Most functions of IL-12, including the induction of IFN-gamma, are compromised in the absence of Stat4. Since the precise role of Stat4 in IFN-gamma induction has not been established, experiments were conducted to examine Stat4 activation of IFN-gamma and other genes required for cytokine-induced expression of IFN-gamma. We first examined IL-12 signaling components. Basal expression of IL-12Rss1 and IL-12Rss2 is decreased in Stat4-deficient cells compared with that in control cells. However, IL-12 was still capable of inducing equivalent phosphorylation of Jak2 and Tyk2 in wild-type and Stat4-deficient activated T cells. We have further determined that other cytokine signaling pathways that induce IFN-gamma production are defective in the absence of Stat4. IL-18 induces minimal IFN-gamma production from Stat4-deficient activated T cells compared with control cells. This is due to defective IL-18 signaling, which results from the lack of IL-12-induced, and Stat4-dependent, expression of the IL-18R. Following IL-12 pretreatment to induce IL-18R, wild-type, but not Stat4-deficient, activated T cells demonstrated IL-18-induced NF-kappaB DNA-binding activity. In addition, IL-12-pretreated Stat4-deficient activated T cells have minimal IFN-gamma production followed by stimulation with IL-18 alone or in combination with IL-12 compared with control cells. Thus, Stat4 activation by IL-12 is required for the function of multiple cytokine pathways that result in induction of IFN-gamma.

Animals↗

Cytokine-stimulated T lymphocyte proliferation is regulated by p27Kip1.

T lymphocyte growth is regulated by the cyclin-dependent kinase inhibitor p27(Kip1). Mice deficient in p27(Kip1) have increased proliferative responses to multiple cytokines, including IL-2, IL-4, and IL-12, but not to anti-CD3. In the absence of p27(Kip1), T cells proliferate faster than control cells, as evidenced by increased [(3)H]thymidine uptake, increased cell growth and division, and an increased number of cells in S phase. Importantly, this regulation is specific for p27(Kip1) in T cells, because hyperproliferation of T cells from mice deficient in p21(Cip1/Waf1) was not observed. In vivo, there is an expansion of activated/memory CD4(+) cells in p27(Kip1)-deficient mice before and after immunization. Furthermore, Ag-stimulated spleen cells from immunized p27(Kip1)-deficient mice demonstrated increased proliferative responses to IL-2 and increased secretion of IFN-gamma. Although IL-4 stimulated proliferative responses are diminished in Stat6-deficient T cells, activated T cells from mice doubly deficient in both p27(Kip1) and Stat6 recover normal proliferative responses to IL-4. Together, these data firmly support a role for p27(Kip1) as a negative regulator of cytokine-stimulated T cell growth.

Adjuvants, Immunologic↗

BtCH(2)TMS-assisted homologation of carboxylic acids: A safe alternative to the arndt-eistert reaction

One-carbon homologation of carboxylic acids is achieved by (i) treatment of an acyl chloride with 1-[(trimethylsilyl)methyl]-1H-1,2, 3-benzotriazole (BtCH(2)TMS) (1) to afford N-(acylmethyl)benzotriazoles 3a-f, followed by (ii) conversion of 3a-f with triflic anhydride into RC(OTf)=CHBt 4a-f, and (iii) the subsequent reaction of 4a-c with NaOCH(3) followed by 1N HCl to afford esters RCH(2)CO(2)R' 7a-c in overall yields of 50-70%. For the aliphatic compounds 5d-f, treatment of 5d-f with p-toluenesulfonic acid followed by TBAF/THF afforded acids RCH(2)COOH 7d-f.

Journal Article↗

An androgen response element mediates LNCaP cell dependent androgen induction of the hK2 gene.

Human glandular kallikrein (hK2) is an androgen regulated protein primarily expressed in the prostate and recently identified as a novel prostate cancer marker. A 5 kb 5' flanking region of the hK2 gene was isolated and sequenced to characterize the regulatory mechanisms for the expression of hK2 in the androgen responsive prostate cell line, LNCaP. Using gene transfer, gel shift, and mutagenesis assays we have identified an ARE in the 5' far upstream promoter region of the hK2 gene that is crucial for its regulation in LNCaP cells. This study further demonstrated that the hK2 upstream ARE plays a predominant role in androgenic response. More interestingly, previously identified AREs in the prostate specific antigen promoter and the hK2 proximal promoter exert little activity in LNCaP cells. This study for the first time identifies a unique ARE that alone mediates the function of the androgen receptor in LNCaP cells in a cell dependent manner. This study also examines the activity of this ARE with 1alpha, 25 dihydroxy-vitamin D3 on the expression of the hK2 gene in LNCaP cells.

Androgens↗

Flt3 ligand induces tyrosine phosphorylation of gab1 and gab2 and their association with shp-2, grb2, and PI3 kinase.

The receptor tyrosine kinase Flt3 has been shown to play an important role in proliferation, differentiation, and survival of hematopoietic stem and progenitor cells. Although some postreceptor signaling events of Flt3 have been characterized, the involvement of Gab family proteins in Flt3 signaling is not known. In this study, we show that both Gab1 and Gab2 are rapidly tyrosine phosphorylated after Flt3 ligand stimulation of Flt3 ligand-responsive cells. They interact with tyrosine-phosphorylated Shp-2, p85, Grb2, and Shc. The results suggest that Gab proteins are engaged in Flt3 signaling to mediate downstream activation of Shp-2 and PI3 kinase pathways and possibly the Ras/Raf/MAPK pathway.

Adaptor Proteins, Signal Transducing↗

Lung cancer and indoor air pollution in rural china.

PURPOSE: Indoor air pollution has been linked with lung cancer in China. In contrast to previous studies conducted in urban areas with high levels of industrial pollution, we undertook a lung cancer case-control study in a rural area of China, where residents live in underground dwellings. We evaluated the effects of radon, wood and coal combustion, cooking oil fumes, and environmental tobacco smoke on lung cancer risk.METHODS: We enrolled 886 lung cancer cases (656 males, 230 females) diagnosed between 1994-98, aged 30-75 years and 1765 frequency matched population-based controls from two prefectures in Gansu Province in Northwestern China. We conducted interviews with subjects or next of kin on smoking, housing characteristics, fuel use and cooking practices. Year-long radon detectors were placed in current and former homes of subjects.RESULTS: Subjects primarily used coal (22%), wood (56%) or a combination of both (22%) for heating. Odds Ratios (OR) for lung cancer rose with increasing percent of time that coal was used to heat homes over the past 30 years (ORs = 1.00, 1.17, 1.35, 1.23 compared to wood only, adjusted to smoking, P for trend = 0.025). Among non-smoking females and males, the OR for ever exposed to environmental tobacco smoke was 1.19, 95% CI = 0.7-2.0 with a significant trend for increasing years of exposure. Fumes from cooking with rapeseed oil increased the risk of lung cancer (OR = 1.56, 95% CI = 1.0-2.5) among non-smoking women. Among these women, occasional and frequent eye and throat irritation during cooking appeared to be associated with increased risk of lung cancer (ORs = 1.00, 1.42, 2.28, p trend < 0.01), whereas, increasing level of smokiness during cooking did not appear to affect risk.CONCLUSIONS: There is a suggestion that coal used for heating, environmental tobacco smoke, and cooking oil fumes contribute to the risk of lung cancer in this rural area of China.

Journal Article↗

Essential role of signal transducer and activator of transcription (Stat)5a but not Stat5b for Flt3-dependent signaling.

The receptor tyrosine kinase Flt3 plays an important role in proliferation and survival of hematopoietic stem and progenitor cells. Although some post-receptor signaling events of Flt3 have been characterized, the involvement of the Janus kinase/signal transducer and activator of transcription (Jak/Stat) pathway in Flt3 signaling has not been thoroughly evaluated. To this aim, we examined whether Flt3 activates the Jak/Stat pathway in Baf3/Flt3 cells, a line stably expressing human Flt3 receptor. Stat5a, but not Stats 1-4, 5b, or 6, was potently activated by Flt3 ligand (FL) stimulation. Interestingly, FL did not activate any Jaks. Activation of Stat5a required the kinase activity of Flt3. A selective role for Stat5a in the proliferative response of primary hematopoietic progenitor cells to FL was documented, as FL did not act on progenitors from marrows of Stat5a(-/-) mice, but did stimulate/costimulate proliferation of these cells from Stat5a(+/+), Stat5b(-/-), and Stat5b(+/+) mice. Thus, Stat5a is essential for at least certain effects of FL. Moreover, our data confirm that Stat5a and Stat5b are not redundant, but rather are at least partially distinctive in their function.

Animals↗

A fully integrated monolithic microchip electrospray device for mass spectrometry

A novel microfabricated nozzle has been developed for the electrospray of liquids from microfluidic devices for analysis by mass spectrometry. The electrospray device was fabricated from a monolithic silicon substrate using deep reactive ion etching and other standard semiconductor techniques to etch nozzles from the planar surface of a silicon wafer. A channel extends through the wafer from the tip of the nozzle to a reservoir etched into the opposite planar surface of the wafer. Nozzle diameters as small as 15 microm have been fabricated using this method. The microfabricated electrospray device provides a reproducible, controllable, and robust means of producing nano-electrospray of a liquid sample. The electrospray device was interfaced to an atmospheric pressure ionization time-of-flight mass spectrometer using continuous infusion of test compounds at low nanoliter-per-minute flow rates. Nozzle-to-nozzle signal intensity reproducibility using 10 nozzles was demonstrated to be 12% with single-nozzle signal stability routinely less than 4% relative standard deviation (RSD). Solvent compositions have been electrosprayed ranging from 100% organic to 100% aqueous. The signal-to-noise ratio from the infusion of a 10 nM cytochrome c solution in 100% water at 100 nL/min was 450:1. Microchip electrospray nozzles were compared with pulled capillaries for overall sensitivity and signal stability for small and large molecules. The microchip electrospray nozzles showed a 1.5-3-times increase in sensitivity compared with that from a pulled capillary, and signal stability with the microchip was 2-4% RSD compared with 4-10% with a pulled capillary. Electrospray device lifetimes achieved thus far have exceeded 8 h of continuous operation and should be sufficient for typical microfluidic applications. The total volume of the electrospray device is less than 25 pL, making it suitable for combination with microfluidic separation devices.

Journal Article↗

Transmission/disequilibrium tests using multiple tightly linked markers.

Transmission/disequilibrium tests have attracted much attention in genetic studies of complex traits because (a) their power to detect genes having small to moderate effects may be greater than that of other linkage methods and (b) they are robust against population stratification. Highly polymorphic markers have become available throughout the human genome, and many such markers can be studied within short physical distances. Studies using multiple tightly linked markers are more informative than those using single markers. However, such information has not been fully utilized by existing statistical methods, resulting in possibly substantial loss of information in the identification of genes underlying complex traits. In this article, we propose novel statistical methods to analyze multiple tightly linked markers. Simulation studies comparing our methods versus existing methods suggest that our methods are more powerful. Finally, we apply the proposed methods to study genetic linkage between the dopamine D2 receptor locus and alcoholism.

Alcoholism↗

Electrofiltration of Aqueous Suspensions.

Electrofiltration of hydrosols in fixed-bed filters was studied experimentally. The experimental variables examined included media type, electric field strength, and suspension pH values. The extent of particle removal was found to improve with the application of the electric field, and lower pH values favor particle collection. The filtrate quality displayed the transient behavior of increasing particle concentration with time. A simple model which assumes that the filter coefficient decreases linearly with the extent of deposition was developed and found capable of predicting the observed behavior. Copyright 2000 Academic Press.

Journal Article↗

Determination of thiols following their separation by CZE with amperometric detection at a carbon electrode.

The amperometric detection (AD) employing a carbon disk electrode as a working electrode to determine the thiol compounds, including cysteine (CYS), glutathione (GSH), 6-thiopurine (TP), and methimazole (MMI), following their separation by capillary zone electrophoresis (CZE) is described in this paper. The detection potential was chosen at +1100 mV and all analytes exhibit good response at this potential on the carbon disk electrode. The reproducibility, linearity, and recovery were evaluated under the optimum conditions. The four analytes can be baseline resolved within 20 min and the detection limits reached about 10(-6) mol/l of magnitude. The method was applied to the separation and determination of the actual thiol samples and the analytical results were satisfactory.

Carbon↗