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Biomedical subjects

W Yang

Publications and source records attributed to W Yang.

At least 379 records · Page 21Linked to original sources
PubMed1997

[A patient with mitral stenosis due to infective endocarditis].

A 51-year-old woman presented with mild stenosis of the mitral valve which had become thickened and rigid due to infective endocarditis, manifesting as persistent fever of up to 40 degrees C and general fatigue of a few days' duration. A harsh systolic murmur was heard. Multiple blood cultures revealed alpha-streptococcus. Echocardiography disclosed asymmetric septal hypertrophy (interventricular septal thickness/posterior wall thickness, 19/14 mm) and systolic anterior wall motion of the mitral valve. Continuous wave Doppler ultrasonography showed a peak left ventricular outflow tract pressure gradient of 170 mmHg. Transesophageal echocardiography revealed vegetations on the anterior mitral leaflet, aortic valve and interventricular septum along the left ventricular outflow tract. In particular, the anterior mitral leaflet was thickened and moved poorly. The calculated mitral valve areas was 1.5 cm2 and peak diastolic left atrium-left ventricle pressure gradient was 7 mmHg. A specimen of the mitral valve did not reveal commissural adhesion, but the anterior mitral leaflet showed marked fibrous thickening caused by scarred vegetation. Based on these findings, the diagnosis was hypertrophic obstructive cardiomyopathy complicated by infective endocarditis and "mitral stenosis". Valvular regurgitation is a common complication of active and healed infective endocarditis. In contrast, infective endocarditis rarely causes valvular stenosis except for stenosis caused by large fungus vegetation.

Cardiomyopathy, Hypertrophic↗
PubMed1997

Macrophages from motheaten and viable motheaten mutant mice show increased proliferative responses to GM-CSF: detection of potential HCP substrates in GM-CSF signal transduction.

Loss of functional hematopoietic cell phosphatase (HCP) underlies severe hematopoietic and immunologic abnormalities in mice homozygous for the motheaten and viable motheaten mutations. These mice die from pulmonary accumulation of macrophages that are regulated by macrophage colony-stimulating factor (M-CSF) and granulocyte (G)-M-CSF. We determined the growth response of motheaten macrophages to the two growth factors and looked for potential HCP substrates in these cells. Motheaten macrophages showed increased proliferative responses to GM-CSF but not to M-CSF, demonstrating that HCP plays a critical role in downregulating GM-CSF mitogenic signaling. Despite the heightened growth responses of the motheaten macrophages to GM-CSF, there were no marked differences between motheaten macrophages and normal controls in GM-CSF-induced phosphorylation of GM-CSFR beta, Jak2, STAT5 and MAPK, indicating that these molecules are not major HCP substrates in GM-CSF signaling. Interestingly, several markedly hyperphosphorylated proteins were detected in the motheaten macrophages, including a novel 126-kDa phosphotyrosine protein that associated with the phosphatase via its SH2 domains, suggesting that these proteins depend on HCP for dephosphorylation and may mediate the heightened growth responses to GM-CSF. Our data indicate that macrophage hypersensitivity to GM-CSF may be a major factor in motheaten pathogenesis and that HCP may dephosphorylate novel substrates critical in GM-CSF mitogenic signaling.

Animals↗
PubMed1997

The mu-opioid receptor down-regulates differently from the delta-opioid receptor: requirement of a high affinity receptor/G protein complex formation.

Chronic opioid treatment of Neuro2A cells stably expressing either delta-opioid receptor (DOR) or mu-opioid receptor (MOR) resulted in agonist-dependent receptor down-regulation. Although there is high homology in the DOR and MOR amino acid sequences, there is an apparent difference in the regulation of the cellular levels of these two receptors. The ability of 24-hr [D-Pen2,D-Pen5]enkephalin (DPDPE) treatment to internalize and down-regulate DORs expressed in Neuro2A remained intact after pertussis toxin (PTX) pretreatment, which uncouples the receptor from G proteins. In contrast, the ability of [D-Ala2,N-MePhe4,Gly-ol5]enkephalin (DAMGO) to internalize and down-regulate MORs in Neuro2A cells was completely abolished by PTX pretreatment. The requirement of functional MOR but not DOR in agonist-induced receptor down-regulation was further demonstrated by site-directed mutagenesis of the receptors. When Asp114 in transmembrane 2 of MOR was converted to alanine, the ability was abolished of DAMGO or morphine to inhibit forskolin-stimulated [3H]cAMP production in Neuro2A cells stably expressing this mutant receptor. There was a parallel decrease in agonist affinity and elimination of the agonist-induced receptor down-regulation. On the other hand, although the equivalent mutation of Asp95 to alanine in DOR likewise resulted in the inability of DPDPE to inhibit [3H]cAMP production, the ability of DPDPE to down-regulate this mutant receptor after 24-hr treatment was unaffected. This difference in MOR and DOR down-regulation could be caused by the differences in the ability of these two receptors to form high affinity complexes with G proteins. DOR retained the ability to form high affinity complexes even after PTX pretreatment or after mutation of Asp95 in transmembrane 2. In contrast, MOR existed only in the low affinity, uncoupled state after PTX pretreatment or after conversion of Asp114 to alanine. Therefore, in Neuro2A cells, agonist-induced opioid receptor down-regulation seems to depend directly on the formation of the high affinity receptor complexes and not on the activation of the receptors and subsequent transduction of the signals.

Animals↗
PubMed1997

Identification of an HMG-like protein involved in regulation of Na+/H+ exchanger expression.

In this study we characterized regulation of the Na+/H+ exchanger promoter in several tissue types. A conserved poly (dA:dT) region was important in regulation of the promoter. Nuclear extracts from rat myocardium and from mouse proximal tubule cells protected the poly (dA:dT) region of the NHE1 promoter. A protein from nuclear extracts also bound to the poly (dA:dT) element in gel mobility shift binding assays. The binding was specific and was removed by mutations in the poly (dA:dT) region. Characterization of the binding to the poly (dA:dT) region in gel mobility shift assays showed that it was reduced by high concentrations of the divalent cations Mg++ and Mn++. The inhibition by divalent cations was reduced by decreasing the pH of the binding assay. N-terminal sequencing of the poly (dA:dT) binding protein showed that it was a member of the HMG (high mobility group) family of nuclear proteins which are important in cell growth and proliferation. The results are the first direct detection of a protein that regulates the NHE1 promoter.

3T3 Cells↗
PubMed1997

Advances in the development of farnesyltransferase inhibitors: substrate recognition by protein farnesyltransferase.

A variety of compounds that show promise in cancer chemotherapy and chemoprevention have been identified as farnesyltransferase inhibitors. These can be classified into mainly two different types of inhibitors, farnesyl diphosphate competitors and CAAX peptidomimetics. The former type acts by competitively inhibiting farnesyltransferase with respect to one of the substrates, farnesyl diphosphate, whereas the latter type acts by mimicking the other substrate, the C-terminal CAAX motif of Ras protein. One example of a farnesyl diphosphate competitor is manumycin, an antibiotic detected in the culture media of a Streptomyces strain. The CAAX peptidomimetics were developed based on the unique property of farnesyltransferase to recognize the CAAX motif at the C-terminus of the protein substrate. Our recent studies have focused on understanding the structural basis of this CAAX recognition. By using in vitro mutagenesis, residues of yeast farnesyltransferase important for the recognition of the CAAX motif have been identified. Two of these residues are closely located at the C-terminal region of the beta-subunit of farnesyltransferase. These and other results on the structural basis of the CAAX recognition may provide information valuable for structure-based design of farnesyltransferase inhibitors.

Alkyl and Aryl Transferases↗
PubMed1997

[Acute fatty liver in pregnancy: a clinicopathologic study].

OBJECTIVE: To investigate the early recognition and management of milder cases of acute fatty liver in pregnancy (AFLP). METHODS: Twelve cases of AFLP treated in our hospital during the past two and half years were retrospectively studied with emphasis on symptoms, laboratory findings, liver biopsy and maternal complications. The 12 cases were classified into 2 groups. Group 1, 6 cases of advanced AFLP diagnosed clinically, were treated in the first year of the study. Group 2, 6 cases of milder AFLP diagnosed by postpartum liver biopsy, were treated during the last one and half years of the study. RESULTS: The mean gestational age at onset was 34 +/- 3 weeks. In the early stage, all cases had malaise, nausea, loss of appetite and epigastric distress followed by jaundice in the third trimester of pregnancy. Laboratory findings included raised transaminases (< or = 300 IU/L) and total serum bilirubin (32.5-510.8 micro mol/L) levels, hypoalbuminemia (18-30 g/L), hypofibrogenemia (< 2.4 g/L), prolonged prothrombin time and prolonged partial thromboplastin time. Maternal complications were frequent including hepatic encephalopathy (9), ascites (9), hypoglycemia (7), renal failure (3), hematemesis (4), preeclampsia (6), and postpartum hemorrhage (5). Cesarean sections were performed in 7 cases. In group 2, both mother and fetuses had 100% survival. However, the mortality of the mothers and fetuses in group 1 were both 50%. CONCLUSIONS: With increasing awareness, especially in the early recognition of AFLP cases and prompt progressive management, including early termination of pregnancy and large dose infusion of fresh frozen plasma, the prognosis of AFLP is obviously improved. Percutaneous liver biopsy should be done when the coagulation tests became normal and the amounts of ascites decreased after delivery.

Acute Disease↗
PubMed1997

[Prevention of bone loss by chlorotrianisene in oophorectomized rats].

OBJECTIVE: To determine the influence of chlorotrianisene on bone metabolism in oophorectomized rats. METHODS: Forty-eight Wistar female rats, 70 days of age, were randomly divided into four groups: SV group (sham operation + vehicle), OV group (oophorectomy + vehicle), SE group (sham (operation + chlorotrianisene) and OE group (oophorectomy + chlorotrianisene). Chlorotrianisene or vehicle 4 ml/kg was given i.p. daily for 45 days from day 7 of being ovariectomized or sham operated. At the time of death, uterine weight was measured, and the thoracic vetebra 12, left tibia were collected and made into decalcified bone specimens for histomorphometry. RESULTS: There were significant difference in the uterine weight among each group. Significant different appearance by bone histomorphometry was seen between OV and the other three groups, but not shown between SV and SE, OE groups. CONCLUSION: These results suggest chlorotrianisene could inhibit bone loss and delay the atrophy of uterus induced by ovariectomy in Wistar female rats. It has protective effects on bone like other estrogen preparations.

Animals↗
PubMed1997

Color Doppler imaging diagnosis of intra-ocular tumor.

OBJECTIVE: To demonstrate the color Doppler imaging (CDI) of intra-ocular tumors and its importance in the diagnosis of these tumors. METHODS: Ninety-two patients with intra-ocular tumors (105 eyes) were examined by using CDI to observe the vasculature of these tumors, and using SAS soft ware to analyze the results. RESULTS: Blood flow signal was found in retinoblastoma, melanoma of choroid, angioma of choroid, angioma of optic disc, Coats' disease, persistent hyperplastic primary vitreous (PHPV) and metastatic tumors of choroid, but not found in choroid osteoma and melanocytoma of optic disc. The blood flow decreases in central retinal artery in choroidal melanoma and also in ophthalmic artery, central retinal artery and posterior ciliary artery in angioma of choroid (P < 0.01). It was found that blood velocity is much faster in choroidal melanoma than in choroidal angioma (P < 0.05). CONCLUSIONS: CDI is very important and helpful in the diagnosis of intra-ocular tumors.

Adolescent↗
PubMed1997

[Suppression of transforming growth factor beta 1 on malignant phenotype in HL-60 cells].

OBJECTIVE: To study the effect of transforming growth factor beta 1 on tumor cells. METHOD: HL-60 cells were transfected with transforming growth factor beta 1 expression vector by electroporation. Stable cell clones resistant to G 418 were obtained after 2-3 week growth with the drug-containing medium. A series of malignant phenotype were compared between transfected and untransfected HL 60 cells. RESULTS: The growth speed of HL-60 cells which overexpressed transforming growth factor beta 1 mRNA decreased significantly. Clonigenecity in soft agarase and tumor formation in athymic mice were lower than those untransfected HL-60 cells. CONCLUSION: Suppression effect of transforming growth factor beta 1 on malignant phenotype in HL-60 cells were demonstrated.

Animals↗
PubMed1997

[Intervention approach and its effect on lowering mortality of ectopic pregnancy in Shanghai].

OBJECTIVE: To explore an effective intervention approach to lower the mortality of ectopic pregnancy. METHODS: We monitored the mortality of ectopic pregnancy during 1987-1995 in Shanghai and experts' audit, focusing on the causes of death from ectopic pregnancy and combining official administration with intervention approach in medical institutions. RESULTS: Misdiagnosis and patient's delay to hospital were the causes of death from ectopic pregnancy. There were 523,299 live births in Shanghai from 1987 to 1989, in which 23 cases died from ectopic pregnancy, with a mortality of 4.40/100,000. After implementing the intervention approach, during 1990-1995, 14 cases of the total 625,206 nancies live birth died from ectopic pregnancy, with a mortality of 2.24/100,000, as compared the two, P < 0.05. Accordingly, ectopic pregnancy as the cause of maternal death dropped from the first leading cause to the fourth. CONCLUSION: Intensive health care education in masses, medical staffs' awareness to ectopic pregnancy, and intervention, early hospitalization, early diagnosis and early therapy can lower the mortality of ectopic pregnancy.

Adult↗
PubMed1997

[Experimental studies and clinical significance of p53 gene mutation in carcinomas of the nasal cavity and paranasal sinuses].

By using PCR-SSCP method, 21 specimens of nasal cavity and paranasal sinuses carcinomas which were freshly frozen and paraffin embedded were detected for the mutation of p53 gene (exon 6). The overall mutation frequency of patients was 67% (14 out of 21), which was 33% (1 out of 3), 50% (3 out of 6), 67% (4 out of 6) and 100% (6 out of 6) respectively in clinical stage I to IV, 33% (2 out of 6), 67% (4 out of 6) and 89% (8 out of 9) respectively in well, moderately and poorly differentiated carcinomas, and 100% (4 out of 4) and 59% (10 out of 17) respectively in lymph-node metastasis and non-lymphnode metastasis. It was not statistically significant when the Chi-square test was applied (P > 0.05), but there was a tendency towards an increase in p53 mutation frequency with highly malignant, poorly differentiated and lymph-node metastasis carcinomas. The results indicate that the mutation of p53 gene plays an important role in the initial and progression of nasal cavity and praranasal sinuses carcinomas. Detection of p53 mutation using the above sensitive and rapid method reveals practical significance for judging malignant level and evaluating prognosis of nasal cavity and paranasal sinuses carcinomas.

Adenocarcinoma↗
PubMed1996

Structure and analysis of the mouse Na+/H+ exchanger (NHE1) gene: homology and conservation of splice sites.

The Na+/H+ exchanger is a widely distributed integral membrane protein that is responsible for pH regulation in mammalian tissues. We have cloned and analyzed the NHE1 isoform of the mouse genomic Na+/H+ exchanger. A clone from a mouse genomic library contained the NHE1 promoter region and the 5'-untranslated region. It also contained the first 121 amino acids of the coding region of the Na+/H+ exchanger. A splice site occurred after amino acid 121, at the same region as in the human NHE1 gene. The deduced amino terminal coding sequence was 76 and 88% identical to the human and rat NHE1 sequences respectively. The 5'-untranslated region was highly homologous to that of other species and two minicistrons contained in the human Na+/H+ exchanger were present in the mouse sequence. The results show that the deduced protein sequence of the mouse NHE1 gene has a high level of homology with other species and that the splice site of the first intron is conserved. These results suggest that the first large intron may play an important role in the NHE1 gene expression.

Amino Acid Sequence↗
PubMed1996

Regulation of Na+/H+ exchanger gene expression. Role of a novel poly(dA.dT) element in regulation of the NHE1 promoter.

In this study we examine regulation of expression of the Na+/H+ exchanger promoter in L6 and NIH 3T3 cells. We have identified a highly conserved poly(dA dT)-rich region that appears to be important in regulation of expression of the NHE1 gene. Deletion or mutation of this region results in dramatic decreases in promoter activity in both L6 and NIH 3T3 cells. In addition, DNase I footprinting experiments demonstrated that this region is protected by nuclear extracts from both cell types, and gel mobility shift assays showed that a protein or proteins specifically binds to the poly(dA dT)-rich element. Using Southwestern blotting, we determined that a 33-kDa protein binds to the poly(dA dT)-containing region. Mutations that abolished protein binding to this element diminished activity of the promoter. Insertion of the poly(dA dT)-rich element into a plasmid containing the SV40 promoter demonstrated that this element can also enhance the activity of a foreign promoter. Together, the results we have presented here show that the poly(dA dT)-rich region is important in regulation of NHE1 expression in different cell types.

3T3 Cells↗
PubMed1996

H19 gene overexpression in atypical multidrug-resistant cells associated with expression of a 95-kilodalton membrane glycoprotein.

The multidrug resistance phenotype of human breast carcinoma MCF-7/AdrVp cells is characterized by overexpression of a 95-kilodalton membrane glycoprotein (p95), accompanied by a marked reduction in intracellular anthracycline accumulation, without overexpression of P-glycoprotein or the multidrug resistance protein. We discovered that the mRNA of the H19 gene is overexpressed in MCF-7/AdrVp cells relative to parental MCF-7 cells or drug-sensitive MCF-7/AdrVp revertant cells. H19 is an imprinted gene with an important role in fetal differentiation, as well as a postulated function as a tumor suppressor gene. Another p95-overexpressing multidrug-resistant cell line, human lung carcinoma NCI-H1688, also displays high levels of H19 mRNA. In contrast, several multidrug-resistant cell lines that overexpress P-glycoprotein or the multidrug resistance protein do not have higher levels of H19 mRNA than their drug-sensitive counterparts. This is the first report of H19 gene overexpression accompanying any form of drug resistance. The association of H19 and p95 gene expression in drug resistance warrants further study.

Base Sequence↗
PubMed1996

Association of hepatic system A amino acid transporter with the membrane-cytoskeletal proteins ankyrin and fodrin.

System A activity is a highly regulated mechanism for the active transport of zwitterionic amino acids into mammalian cells. Monoclonal antibodies generated against a previously unidentified rat liver plasma membrane-associated protein were shown to immunoprecipitate solubilized System A transport activity. The immunoreactive protein was later determined by immunoblotting and peptide microsequencing to be rat liver alpha-fodrin (non-erythroid spectrin). Antibody against ankyrin, a protein that often serves as a bridge between integral membrane proteins and fodrin, also immunoprecipitated System A transport activity. Fractionation of solubilized plasma membrane proteins on sucrose gradients revealed that the System A transporter co-migrated as a complex with fodrin and ankyrin, even in the presence of detergent and urea. In contrast, the System N amino acid transporter does not co-migrate with ankyrin and fodrin, nor does the anti-fodrin antibody immunoprecipitate System N activity. The present data are the first to demonstrate an association between an organic solute transporter and the membranocytoskeletal proteins ankyrin and fodrin.

Amino Acid Sequence↗