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Biomedical subjects

Z Xiao

Publications and source records attributed to Z Xiao.

At least 37 records · Page 2Linked to original sources
PubMed2000

A distinct nuclear localization signal in the N terminus of Smad 3 determines its ligand-induced nuclear translocation.

Smad proteins are intracellular mediators of transforming growth factor beta (TGF-beta) and related cytokines and undergo ligand-induced nuclear translocation. Here we describe the identification of a nuclear localization signal (NLS) in the N-terminal region of Smad 3, the major Smad protein involved in TGF-beta signaling. An NLS-like basic motif (Lys(40)-Lys-Leu-Lys-Lys(44)), conserved among all pathway-specific Smad proteins, not only is responsible for constitutive nuclear localization of the isolated Smad 3 MH1 domain but also is crucial for Smad 3 nuclear import in response to ligand. Mutations in this motif completely abolished TGF-beta-induced nuclear translocation but had no impact on ligand-induced phosphorylation of Smad 3, complex formation with Smad 4, or specific binding to DNA. Hence Smad 3 proteins with NLS mutations are dominant-negative inhibitors of TGF-beta-induced transcriptional activation. Smad 4, which cannot translocate into the nucleus in the absence of Smad 3 or another pathway-specific Smad, contains a Glu in place of the last Lys in this motif. Smad 3 harboring the same mutation (K44E) does not undergo ligand-induced nuclear import. Conversely, the isolated Smad 4 MH1 domain does not accumulate in the nucleus but becomes nuclear enriched when Glu(49) is replaced with Lys. We propose that this highly conserved five-residue NLS motif determines ligand-induced nuclear translocation of all pathway-specific Smads.

Activin Receptors, Type I↗
PubMed2000

Identification of a superimmunoglobulin gene family member overexpressed in benign prostatic hyperplasia .

BACKGROUND: Benign prostate hyperplasia (BPH), a nonmalignant disease with an increasing rate of occurrence associated with advancing age, requires auxiliary markers to help identify its presence and distinguish its progression from prostate cancer. METHODS: Hybridoma technology was used to generate an antibody against a BPH antigen, which was subsequently characterized by Western blot analysis, sequence homology, and RT-PCR. RESULTS: A BPH-associated protein, designated P25/26, was identified that showed a strong sequence similarity with superimmunoglobulin family members, overexpressed in BPH, with lower expression observed in both normal and prostate cancer tissues. CONCLUSIONS: Further studies appear warranted to assess the role that this and other superimmunoglobulin family members may have in the pathogenesis of BPH, and to determine if these glycoproteins have any clinical utility in the differential diagnosis or therapeutic monitoring of BPH.

Adult↗
PubMed2000

Generation of a baculovirus recombinant prostate-specific membrane antigen and its use in the development of a novel protein biochip quantitative immunoassay.

Prostate-specific membrane antigen (PSMA) is a 100-kDa transmembrane glycoprotein identified by the monoclonal antibody 7E11-C5.3 from the human prostate tumor cell line LNCaP. Because of its significant upregulation in androgen refractory and metastatic prostate cancers, PSMA may be a useful prognostic biomarker and a target for developing novel therapeutic strategies. However, the lack of abundant pure PSMA protein and the low efficacy in immunoaffinity isolation from LNCaP cells have hampered the development of clinical assays. In order to obtain a renewable and reliable source of pure antigen, we used the baculovirus/insect cell system to express and purify a recombinant PSMA. A recombinant baculovirus containing a 6x histidine-tagged PSMA gene was generated, from which rPSMA was expressed and purified using cobalt-chelating affinity chromatography. The purity and correct molecular size of rPSMA were demonstrated by gel electrophoresis and mass spectrometry. Glycosidase digestions showed that the oligosaccharides on rPSMA are primarily N-linked high-mannose type. Although the glycosylation is different from the native PSMA, it did not affect the immunoreactivity of rPSMA to antibodies specific for either the intra- or the extracellular domains of PSMA. Finally, the purified rPSMA was successfully used to develop a quantitative PSMA immunoassay using the novel ProteinChip surface-enhanced laser desorption/ionization mass spectrometry technology.

Animals↗
PubMed2000

Mutation of the surface valine residues 8 and 44 in the rubredoxin from Clostridium pasteurianum: solvent access versus structural changes as determinants of reversible potential.

The Pr(i) sidechains of two adjacent valine residues, V8 and V44, define the surface of the rubredoxin from Clostridium pasteurianum and control access to its Fe(S-Cys)4 active site. To assess the effect of systematic change of the steric bulk of the alkyl sidechains, eight single and three double mutant proteins have been isolated which vary G (H), A (Me), V (Pr(i)), L (Bu(i)) and I (Bu(s)) at those positions. X-ray crystal structures of the Fe(III) forms of the V44A and V44I proteins are reported. Positive shifts in reversible potential of up to 116 mV are observed and attributed to increased polarity around the Fe(S-Cys)4 site induced by (1) changes in protein backbone conformation driven by variation of the steric demands of the sidechain substituents and (2) changes in solvent access to the side-chains of ligands C9 and C42. Data for the V44A mutant show that a minor change in the steric requirements of a surface residue can introduce a NH...Sgamma hydrogen bond at the active site and lead to a shift in potential of + 50 mV.

Base Sequence↗
PubMed2000

[An observation of the immuno-persistence after inoculating with the domestic BRD II strain rubella vaccine among infants and young children].

OBJECTIVE: To study the immuno-persistence after inoculating with the domestic BRD II strain rubella vaccine among infants and young children. METHODS: Hemagglutination inhibition (HI) antibody detection method was used to test on children at age 6 to 18 months without rubella infection or rubella vaccine immunization in Yantai city of Shandong province and were selected for the observation of the immuno-persistence against the domestic BRD II strain rubella vaccine from 1995 to 1998. RESULTS: Positive rates of HI antibody among children of 6, 7, 8, 9, 12 and 18 month-old of inoculation were 94.44%, 97.22%, 96.67%, 100.00%, 100.00%, 100.00% and 93.10%, 93.55%, 96.77%, 96.97%, 100.00%, 100.00% (P > 0.05), in one or two years respectively. The geometric mean reverse titers (GMRTs) were about 50% lower than that after 1 month after 1 year. Similar results were found that after 2 years GMRTs was about 50% lower than that after 1 year of inoculation. There was highly significant difference on GMRTs of HI antibody between infants with 6 to 7 month-olds (29.89) and young children with 8 to 18 month-olds (53.00) after 2 years of inoculation (t = 3.58, P < 0.001). CONCLUSION: The immunization schedule at the first dose for BRD II strain rubella vaccine should be started when the child is 8 month old. For the second dose, the immunization schedule used in other developed countries should be referred adopted in China.

Antibodies, Viral↗
PubMed2000

[The ejection of ascoporae of Cordyceps sinensis].

This paper has reported the effect of sunshine to stromata of Cordyceps senensis grown in Kanding, Sichuan and Naqu, Tibet. The ejective time, quantity and germination rate of ascoporaes between the two habitats are different with sunshine. To satisfy the needs of sunshine, moisure and temperature can be raised the ejection and germination of ascorporae.

Animals↗
PubMed2000

[Mutations in the connexin 26 gene in patients with nonsyndromic hearing impairment].

OBJECTIVE: To determine the prevalence and characteristics of deafness-causing mutations in Connexin 26(Cx26, GJB2) gene in Chinese with nonsyndromic hearing impairment(NSHI). METHODS: Study subjects are all Chinese including 16 infants with sporadic congenital deaf-mutism, 39 patients with autosomal recessive hereditary hearing loss, 30 patients with autosomal dominant hereditary hearing loss and 100 normal adults. The subjects were screened for base variations by single-strand conformational polymorphism (SSCP) analysis of the amplified products of polymerase chain reaction (PCR). Those who were found have abnormal conformational band were sequenced. RESULTS: Five kinds of polymorphism were found in 15 cases of controls and six kinds of polymorphism in 10 patients. No mutation was found in Cx26 gene in Chinese with autosomal recessive NSHI. Heterozygous deletion AT at position 299-300 of Cx26 cDNA, which results in premature chain termination, was found in a pedigree with autosomal dominant hereditary nonsyndromic hearing loss. CONCLUSION: The prevalence of deafness-causing mutations in Cx26 gene in Chinese with autosomal recessive NSHI maybe is lower than that of other ethnic groups. Heterozygous deletion AT at position 299-300 of Cx26 cDNA can lead to autosomal dominant hereditary hearing loss (DFNA3).

Asian People↗
PubMed2000

[Neurofibromatosis type 2].

OBJECTIVE: To investigate the clinical characteristics and management strategies of bilateral acoustic neuromas. METHODS: The data of 7 patients with bilateral acoustic neuromas collected between 1990 to 1998 were retrospectively analyzed. RESULTS: Altogether 122 patients with acoustic tumors were treated from 1990 to 1998, in which 7 cases (5.8%, 6 male and 1 female) had bilateral acoustic neuromas. The age at onset of symptoms ranged from 13 to 60 years (average 29.1 years). Progressive hearing loss and tinnitus were the initial symptoms in 4 cases. Either strabismus, ptosis, headache or dysequilibrium was presented in 4 cases. Six cases complicated tumors in the central nervous system and/or other sites. Five cases had cafe au lait spots. One case had posterior subcapsular lenticular opacity. Four cases fell into severe (Wishart) type and 2 into mild (Gardner) type. The tumors were unilaterally removed in 4 patients through the retrolabyrinthine approach (1 case) or the retrosigmoid approach (3 cases). In these 4 patients, one died of central respiratory failure after the operation; two had contralateral tumor removal through retrosigmoid approach 3 weeks after the first surgery. One of the patients died of encephaledema after the surgery. No hearing impairment and facial nerve paralysis occurred in one case operated on through the retrolabyrinthine approach, whereas in those through retrosigmoid approach, 4 ears had hearing loss and 3 sides had facial nerve paralysis. CONCLUSION: The clinical characteristics and treatment strategies for bilateral acoustic neuromas are different from those of unilateral acoustic neuroma. Individualization of management is a prerequisite for the success of the treatment. To avoid injury to the VII and VIII cranial nerves, monitoring the nerve functions during the surgery is important.

Adolescent↗
PubMed1999

Desensitization of G-protein-coupled receptors. agonist-induced phosphorylation of the chemoattractant receptor cAR1 lowers its intrinsic affinity for cAMP.

Agonist-induced phosphorylation of G-protein-coupled receptors has been shown to facilitate the desensitization processes, such as receptor internalization, decreased efficiency of coupling to G-proteins, or decreased ligand affinity. The lowered affinity may be an intrinsic property of the phosphorylated receptor or it may be the result of altered interactions between the modified receptor and downstream components such as G-proteins or arrestins. To address this issue, we purified cAR1, the major chemoattractant receptor of Dictyostelium discoideum by a strategy that is independent of the ligand binding capacity of the receptor. To our knowledge, this represents the first successful purification of a chemoattractant receptor. The hexyl-histidine-tagged receptor was solubilized from a highly enriched plasma membrane preparation and purified by Ni2+-chelating chromatography. The protocol offers a simple way to purify 100-500 micrograms of a G-protein coupled receptor that can be targeted to the plasma membrane of D. discoideum. The Kd value for the purified cAR1 was about 200 nM, consistent with that of receptors that are not coupled to G-proteins in intact cells. In contrast, the affinity of phosphorylated cAR1, purified from desensitized cells, was about three times lower. Treatment of the phosphorylated receptor with protein phosphatases caused dephosphorylation and parallel restoration of higher affinity. We propose that ligand-induced phosphorylation of G-protein-coupled receptors causes a decrease in intrinsic affinity and may be useful in maintaining the receptor's sensitivity at high agonist levels. This affinity decrease may precede other processes such as receptor internalization or uncoupling from G-proteins.

Alanine↗
PubMed1999

Genetic evidence for interactions between yeast importin alpha (Srp1p) and its nuclear export receptor, Cse1p.

The yeast Srp1p protein functions as an import receptor for proteins bearing basic nuclear localization signals. Cse1p, the yeast homolog of mammalian CAS, recycles Srp1p back to the cytoplasm after import substrates have been released into the nucleoplasm. In this report we describe genetic interactions between SRP1 and CSE1. Results from genetic suppression and synthetic lethality studies demonstrate that these gene products interact to ensure accurate chromosome segregation. We also describe new mutant alleles of CSE1 and analyze a new temperature-sensitive allele of CSE1, cse1-2. This allele causes high levels of chromosome missegregation and cell cycle arrest during mitosis at the nonpermissive temperature.

Amino Acid Sequence↗
PubMed1999

Characterization of a novel transplantable orthotopic rat bladder transitional cell tumour model.

An animal tumour model that mimics the human counterpart is essential for preclinical evaluation of new treatment modalities. The objective of this study was to develop and characterize such a model. To accomplish this, the established AY-27 rat bladder transitional cell carcinoma (TCC) cell line was transplanted orthotopically into Fischer CDF344 female rats. AY-27 TCC cells were grown in monolayer cell culture and instilled intravesically as single cell suspensions into bladders that had been conditioned with mild acid washing. Tumour growth was assessed weekly by subjecting the rats to magnetic resonance imaging (MRI). At intervals following implantation and MRI tumour detection, the animals were sacrificed for necropsy, histological examination and immunocytochemical studies. Flow cytometry was also performed for detection of Fas or Fas-ligand expression on AY-27 cells. The overall tumour establishment was 95% (97/102 rats) at 12-50 days, while in a subgroup of animals sacrificed at 16 days, 80 out of 82 animals (97%) developed TCC, the majority of which was superficial. Tumour stage was assessed by gross pathology and light microscopy. Histological examination of the tumour specimens confirmed the presence of grade II-III TCC. Immunocytochemistry confirmed that the tumour model maintained the features of TCC. The changes seen on MRI correlated well with the extent of tumour invasion identified histologically. Patchy carcinoma in situ could be detected histologically 12-13 days post-inoculation, and progressed to papillary tumour or invasive disease thereafter. Neither Fas nor Fas-ligand was expressed on AY-27 cells. The orthotopic AY-27 TCC model is highly reproducible and is ideal for preclinical studies on experimental intravesical therapies.

Animals↗
PubMed1999

Rubredoxin from Clostridium pasteurianum. Structures of G10A, G43A and G10VG43A mutant proteins. Mutation of conserved glycine 10 to valine causes the 9-10 peptide link to invert.

The four cysteine ligands which coordinate the Fe atom in the electron-transfer protein rubredoxin lie on loops of the polypeptide which form approximate local twofold symmetry. The cysteine ligands in the protein from Clostridium pasteurianum lie at positions 6, 9, 39 and 42. Two glycine residues adjacent to the cysteine ligands at positions 10 and 43 are conserved in all rubredoxins, consistent with the proposal that a beta-carbon substituent at these positions would eclipse adjacent peptide carbonyl groups [Adman et al. (1975). Proc. Natl Acad. Sci. USA, 72, 4854-4858]. X-ray crystal structures of the three mutant proteins G10A, G43A and G10VG43A are reported. The crystal structures of the single-site mutations are isomorphous with the native protein, space group R3; unit-cell parameters are a = 64.3, c = 32.9 A for G10A and a = 64.4, c = 32.8 A for G43A. The crystals of the double mutant, G10VG43A, were in space group P43212, unit-cell parameters a = 61.9, c = 80.5 A, with two molecules per asymmetric unit. The observed structural perturbations support the hypothesis that mutation of the conserved glycine residues would introduce strain into the polypeptide. In particular, in the G10VG43A protein substitution of valine at Gly10 causes the 9-10 peptide link to invert, relieving steric interaction between Cys9 O and Val10 Cbeta. This dramatic change in conformation is accompanied by the loss of the 10N-HcO6 hydrogen bond, part of the chelate loop Thr5-Tyr11. The new conformation allows retention of the 11N-HcS9 hydrogen bond, but converts it from a type II to a type I hydrogen bond. This occurs at the cost of a less tightly packed structure. The structural insights allow rationalization of 1H NMR data reported previously for the 113CdII-substituted proteins and of the negative shifts observed in the FeIII/FeII mid-point potentials upon mutation.

Alanine↗
PubMed1999

Modulation of platelet-neutrophil interaction with pharmacological inhibition of fibrinogen binding to platelet GPIIb/IIIa receptor.

The study investigated how drug inhibition of the GPIIb/IIIa receptor influences the interactions between platelets and leukocytes. These interactions are believed to play an important role in the etiology of the acute coronary syndromes. Thirty patients with unstable angina or non-Q-wave myocardial infarction were studied before the administration of tirofiban or placebo and after 4 h and 72 h. Platelet-leukocyte aggregates were characterized in whole blood using three-colour flow cytometry. The leukocyte population was isolated by a nucleic acid probe (LDS 751) and platelet-neutrophil coaggregates identified as particles binding both anti-CD42a-FITC and anti-CD45-PE. Tirofiban decreased by 25% the density of platelets in circulating platelet-neutrophil coaggregates (p <0.01), and prevented the increase induced by platelet agonist stimulation (p <0.0001). The reduction correlated with inhibition of fibrinogen binding to platelet (p <0.0001) and with inhibition of platelet aggregation (p <0.0001). The percentage of neutrophils with bound platelets following platelet agonist stimulation was, however, increased following GPIIb/IIIa inhibition. Thus, inhibition of GPIIb/IIIa receptor promotes platelet-neutrophil adhesion, but markedly reduces the binding density of platelets in the coaggregates.

Aged↗
PubMed1999

Different responses of cerebral vessels to -30 degrees head-down tilt in humans.

This study explored changes of the cerebral circulation and evaluated the responses to weightlessness in 12 volunteers (18-22 yr of age). The velocities, diameters and blood flow volume of the common carotid artery (CCA), internal carotid artery (ICA), vertebral artery (VA) and internal jugular vein (IJV) were measured with color Doppler echogram before and during simulated weightlessness. -30 degrees head-down tilt (HDT) for 45 min was used as a weightlessness simulation model. When the subjects' positions were changed from the supine to -30 degrees HDT, blood flow velocities along the CCA, ICA and IJV decreased significantly (p< 0.05), and their diameters were increased. The subjects were divided into two groups according to measured changes in flow volume of the ICA and IJV: group I with a net in-flow of cerebral blood flow (CBF) and group II with a net out-flow of CBF during HDT. Symptoms were recorded in the two groups during HDT (nasal congestion, sensation of head fullness, headache, and others) and graded on a four-point scale, from absent to serious. Results showed that group I had a higher symptoms score while group II had a lower symptoms score. Although this difference did not reach statistical significance, it suggests that cerebral blood flow changes may be partly responsible for the symptoms observed in subjects during HDT.

Adolescent↗
PubMed1999

[Low doses of mifepristone for emergency contraception].

OBJECTIVE: To investigate the efficacy of three different low doses of mifepristone for emergency contraception, the side effects and the influence to the next menstruation. METHODS: A randomized multicentre trial was conducted in Shanghai. 639 women with regular cycles and history of unprotected intercourse within 120 h of attendance were recruited, and they were randomly assigned to three groups. Group I (n = 214) mifepristone 50 mg was given, group II (n = 214) 25 mg and group III (n = 211) 10 mg. RESULTS: There were eight pregnancies totally, 2 cases in group I, 1 in group II and 5 in group III. After correction for method failure there was only 1 pregnancy in each group and the contraceptive effectiveness rate were 93.4%, 93.3% and 93.8% respectively. The side effects of mifepristone were slight and tolerable and there was significant difference between the 50 mg group and the lower doses (25 mg and 10 mg) groups (P < 0.05) in women with no complaints. There were about 12%-14% women had a early onset of menses and about 25%-28% had a late one, but no significant differences were found among the 3 groups. The average days of delayed onset of next menstruation were significant longer in group I than that in group III (P < 0.05). CONCLUSION: All the 3 doses of mifepristone could be used as an effective emergency contraception.

Adolescent↗
PubMed1999

[Depressive disorders among outpatients in general hospitals].

OBJECTIVE: To investigate the prevalence, recognition and treatment of depressive disorders among outpatients in general hospitals. METHODS: 26,969 outpatients of general hospitals 15 countries were interviewed by GHQ-28, CIDI and physician interview scale in two-stage case identification process. In Shanghai, 583 patients were interviewed by all scales, among them men and women were in 38.0% and 62.0% respectively. RESULTS: Among all the psychological problems, the prevalence of depressive disorders was listed as the first one. The prevalence of major depression and dysthymia in the whole sample was 10.4% and 2.1% respectively and in Shanghai it was 4.0% and 0.6% respectively. The recognized rate of depressive disorders by physician in Shanghai was 21%, which was much lower than 55.6%--the medium among the fifteen countries. The treatment of depressive disorders by physician was inadequate. None of antidepressants was prescribed by any of physician for the recognized depressive disorders in Shanghai. CONCLUSIONS: Depressive disorders are the most common psychological problems in the outpatients of general hospitals, but they are under-recognized and inadequately treated in general hospitals. Reeducation of physician on mental health knowledge must be emphasized by the whole society.

China↗
PubMed1999

[Ankylosing spondylitis in Shantou: clinical experience in fifteen years].

OBJECTIVE: To evaluate the clinical features of ankylosing spondylitis (AS) in Shantou area and improve the diagnostic level and therapeutic effect. METHODS: Clinical and laboratory data, and the methods and effects of therapy were analyzed. Some patients were followed up. RESULTS: 94% of the cases had an insidious onset. Low back pain or discomfort, peripheral arthritis, positive "4" test and pressing tenderness over the sacroiliac joints and lumbar spine were the frequent symptoms and signs. The degree of sacroiliitis and involvement of hip and spine were related to the disease duration. However, hip joint involvement in juvenile onset AS did not relate to the disease duration. Some cases with disease duration as long as 16 years still remained at II of degree sacroiliitis. Clinical improvement was more obvious in the first two years of treatment. Although some patients came to a standstill condition after this period, yet the disease activity might still relapse with withdrawal of the treatment. The rate of adhering to the treatment for 1, 2, and over 5 years was 34.6%, 28.4%, and 10.3% respectively. The radiological changes frequently did not parallel with the clinical manifestations. CONCLUSION: Early diagnosis is of importance in improving the prognosis of AS and adherence to slow-acting anti-rheumatic drug therapy is beneficial in disease controlling. A follow up of more than 3 years is necessary to estimate the therapeutic efficacy, and the radiological change is the key indicator. AS is a heterogenic disease and the risk factors for prognosis should be further studied.

Adolescent↗