Biomedical subjects

Y Wang

Publications and source records attributed to Y Wang.

At least 19 recordsLinked to original sources

PubMed2026

[Analysis of clinical spectrum and genotype characteristics of 9 cases of Fabry disease].

Objective: To investigate the genetic characteristics and clinical phenotypes across different genotypes in patients with Fabry disease. Methods: Clinical data of 9 confirmed FD patients treated from June 2019 to December 2025 at the Affiliated Huai'an No.1 people's Hospital of Nanjing Medical University were retrospectively analyzed. The diagnostic criteria for FD included α-galactosidase A (α-GalA) activity, GLA gene sequencing, globotriaosylsphingosine levels, and renal biopsy findings, supplemented by clinical symptoms and signs. Genetic testing was performed on both the proband and their family members. Proband underwent next-generation sequencing of the GLA gene using the long-range PCR. Family members were verified by conventional PCR combined with Sanger sequencing. Variants were classified according to the 2015 American College of Medical Genetics and Genomics guidelines for sequence variation interpretation. Results: Of the 9 patients, 4 were males and 5 were females. The mean α-Gal A activity was (0.47±0.13) μmol·L-1·h-1 in males and (2.38±0.91) μmol·L-1·h-1 in females. The mean age at diagnosis was (43.0±16.7) years. The main clinical manifestations included renal impairment in 7 cases (proteinuria, chronic kidney disease, or end-stage renal disease), cardiac involvement in 8 cases (myocardial hypertrophy, arrhythmia, etc.), and autonomic nervous system symptoms in 6 cases (hypohidrosis). Pathogenic or likely pathogenic GLA variants were identified in all 9 patients, of which 8 were classified as pathogenic and 1 as a variant of uncertain significance. Three patients underwent family screening: in one case, the variant was possibly inherited from the maternal grandmother; one case was confirmed as a de novo mutation; and in one case, paternal inheritance could not be excluded. Renal biopsy in one patient revealed characteristic myeloid bodies and zebra bodies. Among the 9 patients, 1 received agalsidase α and 8 received agalsidase β, with one case developing infusion-associated reactions after 12 infusions. During the follow-up period, one patient died due to cardiac complications. Conclusions: FD patients exhibit a broad clinical spectrum and diverse genotypes. Atypical presentations should be closely monitored to enable early diagnosis and treatment, thereby improving prognosis.

Humans↗

PubMed2026

Genomic basis of developmental defects of enamel and sex-specific effects.

We conducted a multi-ancestry genome-wide association study (GWAS) of developmental defects of enamel (DDE) in the primary dentition among 6,061 U.S. preschool-aged children (3-5 years). We investigated four DDE phenotypes (demarcated opacities, diffuse opacities, hypoplastic defects, and a combined DDE trait) leveraging main-effect models, joint gene-sex interaction testing (2df), and sex-stratified analyses. SNP-based heritability for the combined DDE trait was estimated at 20%, with concordance analyses robustly supporting a genetic etiology. We identified 39 unique genome-wide significant loci (P<5×10 ), with five surpassing a study-wide Bonferroni-corrected statistical significance criterion (P<1.25×10 9), including Y RNA and ALDH1A1. The main-effect GWAS identified 20 loci, including HBS1L and MYB, genes regulating hematopoiesis with plausible roles in amelogenesis. Joint test and sex-stratified analyses revealed 19 additional loci, including ALDH1A1, TENM2, and DLGAP2, demonstrating sex-specific heterogeneity. Nineteen loci exhibited sex-specific differences after Bonferroni correction (P<2x10-3), including genes involved in retinoic acid signaling (ALDH1A1), odontogenesis (TENM2), and neurodevelopment (DLGAP2, CDH10). Pathway enrichment highlighted ectodermal and synapse organization networks, suggesting shared etiological mechanisms between DDE and systemic conditions like neurofibromatosis and autism spectrum disorder. Notably, no locus generalized in an external GWAS of permanent dentition DDE, underscoring fundamental biological differences in the genetic architectures governing primary versus permanent enamel formation. Crucially, a comprehensive cross-trait pleiotropy lookup against early childhood caries (ECC) revealed no shared genetic architecture, supporting the notion that the established clinical and epidemiological association between DDE and ECC is likely driven by structural defects increasing caries lesion susceptibility rather than genetic pleiotropy. By integrating gene-sex interaction testing, this study offers novel insights into the complex, sexually dimorphic genetic etiology of DDE and augments the biological evidence base that can support the development of precision pediatric dentistry.

developmental defects of enamel↗

PubMed1992

The effect of imagery perspectives on the psychophysiological responses to imagined exercise.

The effect of imagery perspectives, i.e. internal imagery vs. external imagery, on the psychophysiological responses to imagined exercise was investigated in the present study. Thirty male and female college students were randomly assigned to perform either internal imagery, external imagery or simple rest in addition to actual exercise. Metabolic, cardiovascular and perceptual responses were recorded before, during and after imagined exercise, actual exercise and rest. The results indicated that internal imagery resulted in a significant increase in ventilation and this response differed from the control condition. Effort sense was higher with internal imagery compared with external imagery. However, both internal and external imagery produced significant elevations in systolic blood pressure (SBP) from pre- to post-imagery, and these values were identical to those observed with actual exercise. Therefore, some responses to imagery were like those seen during actual exercise. Oxygen consumption (VO2), respiratory rate (RR), respiratory exchange ratio (RER), heart rate (HR) and diastolic blood pressure (DBP) were similar between internal and external imagery. It is concluded that the psychophysiological responses to internal imagery resemble actual exercise more than external imagery.

Adolescent↗

PubMed1992

A yeast protein phosphatase related to the vaccinia virus VH1 phosphatase is induced by nitrogen starvation.

A phosphatase related to the vaccinia virus VH1 phosphatase has been cloned from Saccharomyces cerevisiae. The yeast phosphatase is related to the Schizosaccharomyces pombe cdc25 gene product and to a protein encoded by a mammalian open reading frame known as 3CH134, which is an immediate early gene responding to serum stimulation. The phosphatase activity of the yeast gene product appears to be restricted to the hydrolysis of phosphotyrosine-containing substrates, whereas the vaccinia phosphatase hydrolyzes both phosphoserine- and phosphotyrosine-containing substrates. The mRNA encoding the yeast phosphatase is dramatically induced by nitrogen starvation. Inactivation of the yeast phosphatase gene results in a decrease in growth rate.

Amino Acid Sequence↗

PubMed1992

Expression of Hox-7.1 in myoblasts inhibits terminal differentiation and induces cell transformation.

The terminal differentiation of myogenic cells initiates in the proximal portion of the limb bud whereas the distal region remains undifferentiated and proliferative. The apical ectodermal ridge maintains the progress zone in an undifferentiated state and induces proliferation of limb mesenchymal cells. Hox-7.1, a homeobox-containing gene, is expressed throughout the limb bud when limb outgrowth begins, whereas transcripts are later restricted to distal limb mesenchyme which is the proposed site of positional specification. Transplantation of proximal limb bud tissue into the distal portion of the limb results in a re-expression of Hox-7.1 in the transplanted mesenchyme. Similar grafts result in a positional reassignment to distal structures as well as de-differentiation of the grafted proximal tissue. Because of the association of Hox-7.1 expression with proliferative and undifferentiated cells, we tested whether Hox-7.1 regulates differentiation by transfection of Hox-7.1 complementary DNA into determined myogenic cells which represent one mesenchymal lineage in the limb. Here we report that forced expression of Hox-7.1 blocks terminal differentiation and results in a corresponding decrease in steady-state levels of MyoD1. Consistent with the association of Hox-7.1 with proliferation, Hox-7.1-expressing cells also acquire a transformed phenotype. Forced expression of Hox-8.1, a related Hox-gene, does not affect terminal differentiation indicating that the effects of Hox-7.1 are specific.

Actins↗

PubMed1992

A cluster of hydrophobic amino acid residues required for fast Na(+)-channel inactivation.

The inward Na+ current underlying the action potential in nerve is terminated by inactivation. The preceding report shows that deletions within the intracellular linker between domains III and IV remove inactivation, but mutation of conserved basic and paired acidic amino acids has little effect. Here we show that substitution of glutamine for three clustered hydrophobic amino acids, Ile-1488, Phe-1489, and Met-1490, completely removes fast inactivation. Substitution of Met-1490 alone slows inactivation significantly, substitution of Ile-1488 alone both slows inactivation and makes it incomplete, and substitution of Phe-1489 alone removes inactivation nearly completely. These results demonstrate an essential role of Phe-1489 in Na(+)-channel inactivation. It is proposed that the hydrophobic cluster of Ile-1488, Phe-1489, and Met-1490 serves as a hydrophobic latch that stabilizes the inactivated state in a hinged-lid mechanism of Na(+)-channel inactivation.

Amino Acid Sequence↗

PubMed1992

Exclusion of human proteoglycan link protein (CRTL1) and type II collagen (COL2A1) genes in pseudoachondroplasia.

Patients with pseudoachondroplasia have a skeletal dysplasia with marked short stature. The most common cause of this condition is an autosomal dominant mutation, although autosomal recessive inheritance has been reported. Linkage to 2 cartilage-specific candidate genes, type II collagen (COL2A1) and proteoglycan link protein genes (CRTL1), was tested in 9 autosomal dominant families with pseudoachondroplasia. Tight linkage to these candidate genes was excluded with LOD scores for COL2A1 of -2.45 at theta = 0.05 and for CRTL1 of -7.28 at theta = 0.001. Discordant inheritance of the disease phenotype with each of these genes was also observed. Thus, these 2 candidate genes can be excluded as the cause of disease in these families.

Collagen↗

PubMed1992

Primary structure and receptor-binding properties of a neurokinin A-related peptide from frog gut.

A tachykinin peptide was isolated from an extract of the intestine of the European green frog, Rana ridibunda, and its primary structure was established as: His-Lys-Leu-Asp-Ser-Phe-Ile-Gly-Leu-Met.CONH2. This sequence was confirmed by chemical synthesis and shows two amino acid substitutions (leucine for threonine at position 3 and isoleucine for valine at position 7) compared with neurokinin A. Binding parameters for synthetic [Leu3,Ile7]neurokinin A and mammalian tachykinins were compared using receptor-selective radioligands and crude membranes from tissues enriched in the NK1, NK2 and NK3 receptors. [Leu3,Ile7]Neurokinin A was approx. 3-fold less potent than substance P in inhibiting the binding of 125I-labelled [Sar9,Met(O2)11]substance P (labelled with Bolton-Hunter reagent) to rat submandibular gland (NK1 receptor), 8-fold less potent than neurokinin A in inhibiting the binding of [2-[125I]iodohistidine1]neurokinin A to rat stomach fundus (NK2 receptor) and 6-fold less potent than neurokinin B in inhibiting the binding of 125I-Bolton-Hunter-labelled scyliorhinin II to rat brain (NK3 receptor). Thus the frog neurokinin A-related peptide shows moderate affinity but lack of selectivity for all three tachykinin-binding sites in rat tissues. This non-selectivity is similar to that displayed by the molluscan tachykinin, eledoisin, which also contains an isoleucine residue in the corresponding position in the molecule.

Amino Acid Sequence↗

PubMed1992

Coronary revascularisation in insulin-dependent diabetic patients with chronic renal failure.

Insulin-dependent diabetic patients found to have substantial coronary artery disease at the time of assessment for renal transplantation have 2-year survival of less than 50%. Because most of these patients have no angina symptoms their management is controversial. We tried to find out whether coronary artery revascularisation in such patients might decrease the combined incidence of unstable angina, myocardial infarction, and cardiac death. 151 consecutive insulin-dependent diabetic candidates for renal transplantation underwent coronary angiography. 31 had stenoses greater than 75% in one or more coronary arteries, atypical chest pain or no chest pain, and a left ventricular ejection fraction greater than 0.35. Of these, 26 agreed to be randomly assigned medical treatment (a calcium-channel-blocking drug plus aspirin) or revascularisation (angioplasty or coronary bypass surgery). 10 of 13 medically managed and 2 of 13 revascularised patients had a cardiovascular endpoint within a median of 8.4 months of coronary angiography (p < 0.01). 4 medically managed patients died of myocardial infarction during follow-up. Thus, revascularisation decreased the frequency of cardiac events in insulin-dependent diabetic patients with chronic renal failure and symptomless coronary artery stenoses. These findings suggest that diabetic renal transplant candidates should be screened for silent coronary artery disease, because revascularisation may decrease cardiac morbidity and mortality in this population.

Adult↗

PubMed1992

Endothelin rapidly stimulates mitogen-activated protein kinase activity in rat mesangial cells.

Mitogen-activated protein (MAP) kinases are regarded as switch kinases in the phosphorylation cascade initiated by various agonists. We have investigated whether endothelins (ET), which are constrictor and mitogenic isopeptides, can increase MAP kinase activity in rat mesangial cells, using bovine myelin basic protein (MBP) as a substrate for an in vitro kinase assay. Treatment of quiescent mesangial cells with ET-1 rapidly stimulated a kinase activity which phosphorylated exogenous MBP. This stimulation was dose-dependent, with threshold responses at 1 nM-ET-1. Epidermal growth factor and thrombin also activated this kinase in mesangial cells. We also examined the ET signal transduction pathways leading to activation of MBP kinase. Pertussis toxin had no effect on ET-stimulated MBP kinase activity. Stimulation of protein kinase C by phorbol ester increased MBP kinase activity, and down-regulation of PKC partially inhibited ET-stimulated MBP kinase as well as phorbol ester-stimulated MBP kinase activity. Interestingly, genestein, an inhibitor of protein tyrosine kinases, partially inhibited MBP kinase stimulated by ET but not by phorbol esters. These results suggest that ET stimulates MBP kinase activity in rat mesangial cells via at least two pathways: one which is protein kinase C-dependent and a second one that involves a protein tyrosine kinase. Finally, by raising rabbit antibodies against the two forms of MAP kinase, p44mapk and p42mapk, we demonstrated that both isoforms are expressed in mesangial cells. Antibody alpha 1 Cp42 specifically immunoprecipitated p42mapk and allowed us to demonstrate that ET stimulates MBP kinase activity in the p42mapk immunocomplex. In conclusion, we have provided evidence that, in rat mesangial cells, MAP kinases are rapidly activated by ET-1, a regulatory process that involves at least protein kinase C activation and also a contribution of a tyrosine kinase not yet characterized.

Aluminum↗

PubMed1992

Regulation of recombinant rat tyrosine hydroxylase by dopamine.

Recombinant rat PC12 tyrosine hydroxylase, also called tyrosine 3-monooxygenase [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2], purified from Escherichia coli is in an activated form with a low Km for the tetrahydrobiopterin cofactor and a pH optimum of 6.5. Pretreatment with low levels of the derived product, dopamine, inhibits catalytic activity, increases the Km for the cofactor, and shifts the pH curve towards a more acidic pH optimum. Labeled dopamine binds to tyrosine hydroxylase with high affinity (Kd = 1 microM) but low stoichiometry (r = 0.08 mol/mol of enzyme subunit). The binding of dopamine results in the appearance of a blue-green chromophore with lambda max at approximately 660 nm, which is consistent with the formation of a catecholamine-iron complex. In the absence of dopamine, the recombinant enzyme cannot be further activated by phosphorylation with cAMP-dependent protein kinase, although as much as 1 mol of phosphate is incorporated per mol of subunit. In contrast, the enzyme pretreated with dopamine is activated by phosphorylation in the same fashion and to the same extent as the native hydroxylase. The results suggest that the high-affinity binding of catecholamine products is a pivotal post-translational modification that determines the state of enzyme activation and the response to phosphorylation.

Animals↗

PubMed1992

Synthesis and antitumor activity of 3- and 5-hydroxy-4-methylpyridine-2-carboxaldehyde thiosemicarbazones.

To develop an alpha-(N)-heterocyclic carboxaldehyde thiosemicarbazone with clinical utility as an anticancer agent, two analogues, 3-hydroxy-4-methylpyridine-2-carboxaldehyde thiosemicarbazone (3-HMP) and 5-hydroxy-4-methylpyridine-2-carboxaldehyde thiosemicarbazone (5-HMP), of 5-hydroxypyridine-2-carboxaldehyde thiosemicarbazone (5-HP) have been designed and synthesized by two different methods. 3-HMP and 5-HMP both showed better antitumor activity than their respective parent compounds, 3-hydroxypyridine-2-carboxaldehyde thiosemicarbazone and 5-HP, in mice bearing the L1210 leukemia.

Animals↗

PubMed1992

Regulatory light-chain Cys-55 sites on the two heads of myosin can come within 2A of each other.

The di-thiol reagent, 5,5'-dithiobis (2-nitrobenzoic acid) is shown to induce disulfide bond formation between Mercenaria regulatory light-chain Cys-55 sites on either head of scallop hybrid myosin. This indicates that these two sites on opposite heads of myosin can come within 2A of each other and this confirms a prediction based on earlier data [Chantler, Tao and Stafford (1991) Biophys. J. 59, 1242-1250]. Results demonstrate that myosin heads in solution show a considerable mutual freedom of movement which can be monitored by probes in the vicinity of regulatory light-chain residue 55. Implications for light-chain movement on the myosin head are discussed.

Animals↗

PubMed1992

Cell transformation and activation of pp60c-src by overexpression of a protein tyrosine phosphatase.

The kinase activity of pp60c-src is specifically and transiently increased during mitosis and repressed during interphase. Loss of cell-cycle control of pp60c-src occurs on mutation of Tyr527 to Phe or when pp60c-src is associated with polyoma middle-T-antigen, and these conditions result in cell transformation or tumorigenesis. In both cases, pp60c-src has elevated kinase activity which is maintained throughout the cell cycle and accompanied by dephosphorylation of the carboxy-terminal negative regulatory Tyr527 site, or mimicry of Tyr527 dephosphorylation in the case of the mutant. Here we report that overexpression of the receptor-like protein tyrosine phosphatase PTP alpha results in persistent activation of pp60c-src kinase, with concomitant cell transformation and tumorigenesis. In PTP alpha-overexpressing cells, the pp60c-src kinase activation is accompanied by dephosphorylation at Tyr527, and direct dephosphorylation of this site by purified PTP alpha occurs in vitro. Our results suggest that PTP alpha is involved in the regulation of cell proliferation, exerting at least some of its effects through pp60c-src kinase, and has oncogenic capability when overexpressed.

Amino Acid Sequence↗

PubMed1992

Preliminary crystallographic analyses of the N-terminal lobe of recombinant human serum transferrin.

The N-terminal lobe of recombinant human serum transferrin (residues 1 to 337) has been crystallized in a form suitable for high-resolution three-dimensional X-ray crystallographic analyses. Crystals are of the orthorhombic space group P2(1)2(1)2(1), with unit cell dimensions of a = 44.9 A, b = 57.0 A and c = 135.9 A, and diffract to beyond 2 A resolution. Further studies show that isomorphous crystals of specifically designed mutants of this protein can also be grown. Structural studies of both recombinant and mutant protein forms will provide a basis for understanding the mechanism by which human serum transferrin functions.

Crystallization↗

PubMed1992

Binding of dicyclohexylcarbodiimide to aspartate-155 or glutamate-166 of cytochrome b6 in a cytochrome bf complex isolated from spinach thylakoids.

In a recent study [Wang & Beattie (1991) Arch. Biochem. Biophys. 291, 363-370], we reported that dicyclohexylcarbodiimide (DCCD) inhibited proton translocation in the cytochrome bf complex reconstituted into proteoliposomes and was bound selectively to cytochrome b6. To establish the site of binding of DCCD on cytochrome b6, the cytochrome bf complex labeled with [14C]DCCD was selectively digested with chymotrypsin and trypsin. A 17-kDa fragment containing radioactive DCCD and the heme moiety was obtained after chymotrypsin digestion, while a 12.5-kDa fragment containing both radioactive DCCD and the heme moiety was obtained after trypsin digestion, suggesting that the site of DCCD binding might be on aspartate-140, aspartate-155, or glutamate-166. Extensive digestion of cytochrome b6 isolated from a [14C]DCCD-labeled cytochrome bf complex with trypsin followed by isolation and sequencing of two radioactive peptides obtained revealed that DCCD is bound at either residue aspartate-155 or residue glutamate-166 localized in amphipathic extramembranous helix IV. In addition, the cytochrome bf complex labeled with [14C]DCCD was reconstituted into liposomes and digested with trypsin. Three fragments of 9.3, 10.5, and 11.5 kDa were obtained, suggesting that the four-helix model for the topography of cytochrome b6 in the membrane is correct.

Amino Acid Sequence↗

PubMed1992

The disulfide bridge pattern of snake venom disintegrins, flavoridin and echistatin.

Flavoridin and echistatin, isolated from the venom of Trimeresurus flavoviridis and Echis carinatus, respectively, belong to the disintegrin family of integrin beta 1 and beta 3 inhibitors of low molecular weight RGD-containing, cysteine-rich peptides. Since disulfide bonds are critical for expression of biological activity, we sought to determine their location in these two proteins. In flavoridin, direct evidence for the existence of linkage between Cys4-Cys19 and between Cys45 and Cys64 was obtained by analysis of proteolytic products, and indirect evidence suggests links between Cys6-Cys14 and Cys13-Cys36. In echistatin, links between Cys8-Cys37 and Cys20-Cys39 were identified by direct chemical analysis.

Amino Acid Sequence↗

PubMed1992

Guanine residues in d(T2AG3) and d(T2G4) form parallel-stranded potassium cation stabilized G-quadruplexes with anti glycosidic torsion angles in solution.

We report below on proton NMR studies of the G-quadruplex structure formed by the human telomere sequence d(T2AG3) and the tetrahymena telomere sequence d(T2G4) in K cation containing solution. We observe well-resolved proton NMR spectra corresponding to a G-quadruplex monomer conformation predominant at 50 mM K cation concentration and a G-quadruplex dimer conformation predominant at 300 mM K cation concentration. By contrast, d(T2AG3T) and d(T2G4T) form only the G-quadruplex monomer structures independent of K cation concentration as reported previously [Sen, D., & Gilbert, W. (1992) Biochemistry 31, 65-70]. We detect well-resolved resonances for the exchangeable guanine imino and amino protons involved in G-tetrad formation with the hydrogen-bonded and exposed amino protons separated by up to 3.5 ppm. The observed NOEs between the amino and H8 protons on adjacent guanines within individual G-tetrads support the Hoogsteen pairing alignment around the tetrad. The imino protons of the internal G-tetrads exchange very slowly with solvent H2O in the d(T2AG3) and d(T2G4) quadruplexes. The nature and intensity of the observed NOE patterns establish formation of parallel-stranded right-handed G-quadruplexes with all anti guanine glycosidic torsion angles. A model for the parallel-stranded G-quadruplex is proposed which is consistent with the experimental NOE data on the d(T2AG3) and d(T2G4) quadruplexes in solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗