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Biomedical subjects

W Yang

Publications and source records attributed to W Yang.

At least 415 records · Page 23Linked to original sources

Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1.

SHP-1 is an SH2-containing cytoplasmic tyrosine phosphatase that is widely distributed in cells of the hematopoietic system. SHP-1 plays an important role in the signal transduction of many cytokine receptors, including the receptor for erythropoietin, by associating via its SH2 domains to the receptors and dephosphorylating key substrates. Recent studies have suggested that SHP-1 regulates the function of Jak family tyrosine kinases, as shown by its constitutive association with the Tyk2 kinase and the hyperphosphorylation of Jak kinases in the motheaten cells that lack functional SHP-1. We have examined the interactions of SHP-1 with two tyrosine kinases activated during engagement of the erythropoietin receptor, the Janus family kinase Jak-2 and the c-fps/fes kinase. Immunoblotting studies with extracts from mouse hematopoietic cells demonstrated that Jak2, but not c-fes, was present in anti-SHP-1 immunoprecipitates, suggesting that SHP-1 selectively associates with Jak2 in vivo. Consistent with this, when SHP-1 was coexpressed with these kinases in Cos-7 cells, it associated with and dephosphorylated Jak2 but not c-fes. Transient cotransfection of truncated forms of SHP-1 with Jak2 demonstrated that the SHP-1-Jak2 interaction is direct and is mediated by a novel binding activity present in the N terminus of SHP-1, independently of SH2 domain-phosphotyrosine interaction. Such SHP-1-Jak2 interaction resulted in induction of the enzymatic activity of the phosphatase in in vitro protein tyrosine phosphatase assays. Interestingly, association of the SH2n domain of SHP-1 with the tyrosine phosphorylated erythropoietin receptor modestly potentiated but was not essential for SHP-1-mediated dephosphorylation of Jak2 and had no effect on c-fes phosphorylation. These data indicate that the main mechanism for regulation of Jak2 phosphorylation by SHP-1 involves a direct, SH2-independent interaction with Jak2 and suggest the existence of similar mechanisms for other members of the Jak family of kinases. They also suggest that such interactions may provide one of the mechanisms that control SHP-1 substrate specificity.

Animals↗

Regulation of NHE-1 promoter in mammalian myocardium.

The Na+/H exchanger (NHE-1) is an integral membrane protein responsible for intracellular pH regulation in the myocardium and other tissues. The NHE-1 isoform is universally distributed in mammalian cells. We examined regulation of a 1.1-kb fragment of the NHE-1 promoter in neonatal rat cardiomyocytes. Deletion of most of the promoter up to an AP-2 site reduced activity 75%. Further deletion of the promoter or mutation of the AP-2 site reduced or eliminated activity almost completely. Gel mobility shift assay showed that purified AP-2 protein or AP-2-like protein from nuclear extracts of isolated myocytes can bind to DNA of the NHE-1 protein. External acidosis did not cause increased transcription from the promoter. Removal of serum from the medium reduced activity of the NHE-1 promoter. The elements responsible for activation of the promoter by serum were contained within both the 1.1-kb and AP-2-containing region. The results show that the cis-acting putative AP-2 site and the presence of serum are important in NHE-1 expression, whereas external acidosis had no direct effect on the promoter.

Acidosis↗

Respiratory infections and the autumn increase in asthma morbidity.

Unexplained autumn increases in hospital admissions for asthma have been reported in many countries, including the United States, Canada, England and Wales. To investigate the role of infection, the association was tested between hospital admissions for asthma and respiratory infections among preschool children in Metropolitan Toronto, Canada during the period 1981 to 1989. The seasonal pattern in overall hospital utilization was assessed by admissions for nonrespiratory diseases. Time series analysis was used to remove potentially confounding temporal trends and the influence of correlated errors. A fourfold increase in asthma admissions occurred between July and October unaccompanied by similar increases in nonrespiratory admissions. Admissions began increasing during the third week of August, peaked during the third week in September, and slowly decreased during November and December. After adjusting for serial correlation, trends, climate, ambient air pollution and aeroallergens, the seasonal pattern of respiratory infection explained 14% of the variance in asthma admissions. Based on seasonal patterns, respiratory infection is the major identifiable risk factor for the large autumnal increase in asthma admissions.

Air Pollutants↗

Expression of multidrug resistance-associated protein (MRP) mRNA in blast cells from acute myeloid leukemia (AML) patients.

A specific and quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay was developed for measuring the mRNA of the multidrug resistance-associated protein (MRP). A region corresponding to bp 3897-4471 of MRP cDNA is amplified, which encompasses approximately half of the second nucleotide-binding domain (NBD2). In two multidrug resistant (MDR) sublines of the HL-60 human acute myeloid leukemia (AML) cell line which overexpress MRP but not P-glycoprotein, the assay detects elevated levels of MRP mRNA (4- to 8-fold) relative to the drug-sensitive parental cells (designated HL-60/W). Blast cells from 24 patients with AML were also studied for MRP expression using this RT-PCR method. Expression of MRP was normalized for that of beta-actin in the blast cells, which was also determined by RT-PCR. All of these blast cell samples had MRP expression that was detectable after 35 PCR cycles. Eighteen of these patients samples had levels of expression of MRP mRNA equal to or less than that expressed by HL-60/W cells. In six patient blast cell specimens, the expression of MRP mRNA was up to 1.7-fold higher than that of HL-60/W cells. In 21 specimens, the steady-state intracellular accumulation of daunorubicin (1 microgram/ml, 3h) was also determined. The blast cells with MRP mRNA expression higher than HL-60/W had a lower median accumulation of daunorubicin compared to those whose MRP expression was less than HL-60/W, suggesting a functional defect in drug transport in the cells with higher MRP expression; a similar trend toward lower daunorubicin accumulation was also noted in the one-third of samples that displayed the highest expression of MDR1 mRNA (also determined by RT-PCR). These studies illustrate the range of expression of MRP in AML blast cell specimens. The identification of MRP overexpression in MDR AML cell lines and in some AML patient blast cells with low intracellular daunorubicin accumulation warrants further study of MRP as a component of clinical drug resistance in AML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[A PCR marker-based selection for resistance to bacterial blight in rice].

Molecular marker-based selection in plant breeding requires not only suitable molecular markers closely linked to the known genes, but a simple, economic and reliable analyzing technique. We report here a useful PCR marker for genetic diagnostics in breeding for resistance to rice bacterial blight. Xa21 is a newly found gene of rice which confers resistance to bacterial blight caused by Xanthomonas oryzae pv. oryzae. We produced two F2 populations between one resistant line IRBB21 containing Xa21 and two susceptible varieties, respectively. One PCR marker, PB78, detected polymorphism between the susceptible varieties and the resistant line. Cosegregation between Xa21 and PB78 was studied in the two F2 populations. The results showed that Xa21 was closely linked to the molecular marker, the crossing over value was 2.48%. Marker-based selection revealed that 100% of the plants with homozygous resistant genotype of PB78 showed resistance to bacterial blight. The available approaches detecting molecular markers in plant breeding are also discussed.

Base Sequence↗

[Study on ultrastructure morphology of fine needle aspiration of mediastinal and lung lesions].

Specimens of Mediastinal lesions and lung masses collected by fine needle aspiration (FNA) was examined with both light and transmission electron microscopy. Sixty eight specimens (9 mediastinal and 40 lung masses, 4 metastatic chest masses and 15 metastatic lymph nodes from lung cancer) from 104 cases (60.5%) were satisfactory for evaluation. With light microscopy, the nature of the lesions was assessed and the ultrastructural features of the lesions were evaluated with transmission electron microscopy. Diagnosis of histologic type of the lesions by light microscopy was consistent with that by transmission electron microscopy at a conformity rate of 50.4%. The results indicate that ultrastructural features are valuable in ascertaining histologic type of the lesions.

Adenocarcinoma↗

[Effect of zhuyu huatan decoction for cellular and humoral immunity in cerebral hemorrhage].

Fifty-one patients of cerebral hemorrhage were observed on controlled study which were treated with the Zhu-Yu Hua-Tan Decoction (ZYHTD) and Western medicine. The results revealed that ZYHTD could reduce the serum IgG (P < 0.05), and lymphocyte transformation rate (P < 0.05). Meanwhile, the patient's health condition of treated group was better than the control group in the fields of eliminating brain hematoma, evaluating patients condition score in TCM and compromised neurologic function (P < 0.05). It is assumed that there is positive significance in anti-inflammatory effect and promoting the absorption of brain hematoma in the acute phase of cerebral hemorrhage.

Adult↗

Modification of the cytoplasmic domain affects the subcellular localization of Golgi glycosyl-transferases.

Our goal was to engineer a Golgi glycosyltransferase epitope-tagged on its cytoplasmically exposed, short, N-terminal domain that gave normal subcellular localization. Partial replacement of the cytoplasmic tail of human alpha-2,6-sialyltransferase (SialylT) with the negatively charged myc or FLAG epitope resulted in almost complete mislocalization of the chimera expressed in Vero cells. A granular cytoplasmic staining pattern was seen by immunofluorescence. Spacing the negatively charged residues progressively outward from the negative N-terminus resulted in increasingly more normal localization of myc or FLAG-tagged protein to a juxtanuclear Golgi-like distribution. Substitution of a neutrally charged VSV-G sequence for these tags resulted in normal localization of the chimera to the juxtanuclear Golgi region. Insertion of the myc epitope within the N-terminal domain of the short form of bovine beta-1,4-galactosyltransferase (GalT) gave a chimeric protein that mislocalized in BHK cells. No signal was detected with a monoclonal anti-epitope antibody indicating that the myc epitope was masked. Placement of myc or FLAG epitopes at the NH2-terminus of human N-acetylglucosaminyltransferase I (GlcNAc-T) resulted in chimeric proteins that in Vero cells displayed little Golgi localization. We conclude that positioning of negative charge, in particular, close to the membrane, typically produces a failure of type II Golgi glycosyltransferases to exit the ER/CGN, presumably due to quality control mechanisms. These proteins may be successfully epitope-tagged on their N-terminal domain either using a neutral or positively charged sequence or spacing any negatively charged sequence out from the membrane.

Amino Acid Sequence↗

Pharmacology of the human gamma-aminobutyric acidA receptor alpha 4 subunit expressed in Xenopus laevis oocytes.

The human gamma-aminobutyric acidA (GABAA) receptor alpha 4 subunit was recently cloned and characterized pharmacologically using radioligand binding techniques. These studies suggested that alpha 4 subunits confer a novel diazepam-insensitive binding site. To further investigate the pharmacology of the alpha 4 subunit, we expressed human alpha 4 beta 2 gamma 2L subunit combinations in oocytes and compared the expression and pharmacology of these receptors with alpha 1 beta 2 gamma 2L, beta 2 gamma 2L, and other possible binary subunit combinations. Apparent GABA affinity was 2-3-fold higher for alpha 4 beta 2 gamma 2L than for alpha 1 beta 2 gamma 2L receptors. Functional modulation of receptors by benzodiazepine-site ligands and other classes of allosteric modulator were assayed over a broad concentration range (0.01-100 microM) on currents that were 10% of the maximum GABA response. Diazepam (0.01-1 microM) did not modulate GABA responses at alpha 4 beta 2 gamma 2L receptors, whereas it increased alpha 1 beta 2 gamma 2L responses by approximately 110%. Bretazenil (0.01-1 microM), a benzodiazepine partial agonist, induced higher efficacy modulation of alpha 4 beta 2 gamma 2L receptors (approximately 83%) than of alpha 1 beta 2 gamma 2L (approximately 25%). The benzodiazepine antagonist flumazenil (0.1-10 microM) unexpectedly potentiated alpha 4 beta 2 gamma 2L responses up to approximately 41%, and the benzodiazepine partial inverse agonist Ro15-4513 (1 microM) potentiated alpha 4 beta 2 gamma 2L responses by approximately 63%. Two other benzodiazepine-site ligands, CGS-9895 and methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate, had qualitatively similar effects at alpha 1 beta 2 gamma 2L and alpha 4 beta 2 gamma 2L. Modulators such as pentobarbital, 3 alpha-hydroxy-5 alpha-pregnan-20-one, mefenamic acid, and loreclezole also induced similar potentiation at both subtypes of receptor. The pharmacology conferred by the alpha 4 subunit was similar to that conferred by the alpha 6 subunit, to which it shows highest levels of homology, but the two subunits differ in sensitivity to the beta-carboline methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate. Properties of the alpha 4-containing receptors are consistent with diazepam-insensitive binding sites found in cerebral cortex and other forebrain structures. Characterization of these receptors should further our understanding of mechanisms underlying the behavioral effects of GABA modulators and help in the design of drugs with improved, or novel, therapeutic profiles.

Animals↗

A neglected avulsion fracture of calcaneal tuberosity associated with diabetes mellitus: a case report.

Although tuberosity calcaneal fracture is rarely found, we report here a neglected avulsion (so-called "beak") fracture of the tuberosity. The etiology of this fracture is presumed to be, in this old female, diabetic (diabetes mellitus) with accompanying osteoporosis. As it was neglected and long-standing, the Achilles tendon lengthening was required on the surgical intervention.

Aged↗

PCR analysis of half-seeds of cereal crops and its application in marker-assisted selection and breeding.

A simple and rapid PCR method was adapted to DNA analysis of cereal seeds. Half-seeds of rice, wheat, and maize were treated with an extraction buffer and the resulting supernatants were used in PCR and RAPD reactions. PCR products amplified from the half-seed DNA extracts were identical with that from leaf tissue DNA extracts when the same specific primers were used in PCR reactions. The remaining half-seeds with embryos could still germinate normally. The half-seed PCR analysis was applied to the identification of resistant genotypes of rice bacterial blight, and it was proved effective in plant breeding and genetic studies.

Breeding↗

[Study on platelet antioxidant enzyme activity and platelet granule membrane glycoprotein in patients with pregnancy induced hypertension].

OBJECTIVE: To evaluate the platelet antioxidant enzyme activity and platelet activation degree in patients with pregnancy induced hypertension (PIH). METHODS: A monoclonal antibody specific for alpha-granule membrane protein (GMP-140) of platelet was used to evaluate the platelet (plt) activation degree in 44 cases with PIH and 28 cases of normal pregnant women. Meanwhile, the platelet antioxidant enzyme (superoxide dismutase, SOD; catalase, CAT) activity were determined. RESULTS: Platelet SOD activity of PIH (22.08 +/- 7.66 U/10(9) plt) was markedly lower than that of the controls (26.67 +/- 7.59 U/10(9)plt, P < 0.01). There was no difference between the CAT activity of PIH and controls (9.26 +/- 4.53 K/10(12) plt, 8.57 +/- 3.69 K/10(12) plt, P > 0.05). The number of GMP-140 molecules on platelet surface and serum levels of PIH (2073 +/- 902 molecules/plt, 4.65 +/- 1.74 molecules/L x 10(-13) were significantly higher than those of the normal pregnant women (1319 +/- 716 molecules/plt, 1.69 +/- 0.78 molecules/L x 10(-12), P < 0.01). Correlation analysis between GMP-140 on platelet surface, GMP-140 in the serum and SOD activity of PIH showed definite negative correlation (r = -0.601, -0.670 respectively, P < 0.05). CONCLUSIONS: The decline of platelet antioxidant enzyme activity (especially SOD) and platelet activation could play an important role in the pathophysiological changes in PIH. The platelet SOD activity and GMP-140 could be new index of platelet hyperactivity.

Adult↗

[The clinical observations on 110 cases of adhesive otitis media].

The treatment of the adhesive otitis media (AOM) remains a challenge to the otologists. This paper analysed 110 cases of AOM (120 ears) collected during 25 years from 1967 to 1992. The clinical observation found that the lesions of AOM affected all parts of the middle ear, even the round and oval windows. There were various degrees of tympanic fibrous adhesions and atelectatic tympanum in these cases. After the tympanic adhesions were surgically separated and the lesions were removed, the silastic film or a slice of the homologous cartilages were put into the tympanum to prevent a new adhesion. It was showed that the silastic film was frequently enveloped in a capsule formed by the fibrous collagenous tissue and other extensive adhesions were existed around the capsule. But the cartilage slice caused the slighter pathological reactions. However, their hearing did not recovery to an available level. Therefore the further studies for the treatment of AOM are necessary.

Adolescent↗

[Endoscopic sclerosing in the prevention of recurrent esophageal variceal bleeding].

Two hundred and forty one patients with previous bleeding from esophageal varices caused by liver cirrhosis were treated with fiberoptic endoscopic injection sclerotherapy (EIS). The result was desirable. 217 patients were followed. The mean follow-up time was 63. 15 months. The median time was 58 months. Rebleeding rate was 15.21% (33 cases). The total 5-year survival rate was 59%; patients with Child A, B and C were 65% and 35%, respectively. The mortality rate was 10. 60% (23 cases), among them 12 were caused by rebleeding. EIS is an effective method for preventing from rebleeding. Multiple and periodic injections reduce rebleeding rate. EIS increase the 5-year survi al rate by reducing rebleeding rate.

Adult↗

[The preventing and treating effects of electro-acupuncture on cholelithiasis in golden hamster].

In this study, the 38 golden hamsters, male and female each half, were divided into four groups: the control and control treating groups to feed normal foods; cholelithiasis model and model treating groups to feed special diet, which made high fat, high cholesterol and high carbohydrates to cause the cholelithiasis model of hamsters. After 30 day, the natural formation rate of gallstone rose to 50% (contral group), while model group, the formation rate was 100%. On the 30th day, the treatment was carried out. The control treating group and model treating group were acupunctured at Yanglingquan(G 34) and Qimen(Liv 14) through Riyue(G 24) on the right side of body respectively by electrotherapy. The period of treatment was total 7 days, once everyday and 10 min every once. The results showed: (1) In control treating group, the natural formation rate of gallstone of normal hamsters was dropped from 50% to 10%, the number of gall-tones was reduced markedly(P < 0.05) and number of huge gallstones was dropped to zero(P < 0.01). (2) In the cholelithiasis model treating group, the treatment of electrotherapy could significantly reduced the formation rate of cholelithiasis, the number of gallstones and the huge gall-stones(P < 0.05 or P < 0.01). Also, content of the cholesterol in plasma and bile were reduced, but the contents of the cholic acid secreted from the liver were obviously increased in the model hamsters. It was significant difference to compared with model group(P all < 0.05). (3) The electrotherapy increased the rhythmic actions and frequency of Oddi's sphincter electromyogram markedly(P < 0.05, P < 0.01) as well as secretion of hepatic bile(P < 0.05, P < 0.01). The effects of electrotherapy could continued 30 to 40 minutes. The results suggest that some points to acupuncture with electrotherapy can reduce the contents of cholesterol in plasma and bile, and increase the volumes of secretion of cholic acid, thus inhibit the crystallization of cholesterol from bile. At the sometime, the electrotherapy causes the rhythmic contractions of Oddi's sphincter and increase the secretion of bile, so the gallstones are discharged on its own initiative. Therefore the cholelithiasis is cured by acupuncture.

Animals↗

[Studies on microscopic characteristics of atmospheric particles].

Distribution of 15 elements on the surface of and morphological characteristics of 776 atmospheric particles collected from six air monitoring spots in Taiyuan City, Shanxi Province, were analyzed with scanning electronic microscopy and energy dispersive X-ray spectrometry, to study their chemical compositions in air pollution. Results showed silicon and aluminum were abundant in the particles, accounting for 49.4% and 25%, respectively, which indicated they were major components of the particles. Contents of lithophilic elements, such as silicon, aluminum and potassium, on the particle surface were decreased relatively with gradual decrease of particle diameter. Silicon and aluminum in the particles were detected frequently, also, accounting for 96.55% and 89%, respectively, which indicated alumina-silicate particles accounted for the dominant part in atmospheric aerosol, and dust particles from varied sources showed different characteristics and distributions.

Air Pollutants↗