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D Y Wang

Publications and source records attributed to D Y Wang.

At least 55 records · Page 3Linked to original sources

Divergence time estimates for the early history of animal phyla and the origin of plants, animals and fungi.

In the past, molecular clocks have been used to estimate divergence times among animal phyla, but those time estimates have varied widely (1200-670 million years ago, Ma). In order to obtain time estimates that are more robust, we have analysed a larger number of genes for divergences among three well-represented animal phyla, and among plants, animals and fungi. The time estimate for the chordate-arthropod divergence, using 50 genes, is 993 +/- 46 Ma. Nematodes were found to have diverged from the lineage leading to arthropods and chordates at 1177 +/- 79 Ma. Phylogenetic analyses also show that a basal position of nematodes has strong support (p > 99%) and is not the result of rate biases. The three-way split (relationships unresolved) of plants, animals and fungi was estimated at 1576 +/- 88 Ma. By inference, the basal animal phyla (Porifera, Cnidaria, Ctenophora) diverged between about 1200-1500 Ma. This suggests that at least six animal phyla originated deep in the Precambrian, more than 400 million years earlier than their first appearance in the fossil record.

Animals↗

Inositol phosphoglycans in diabetes and obesity: urinary levels of IPG A-type and IPG P-type, and relationship to pathophysiological changes.

Measurements have been made, in adult male diabetic patients and control subjects, of the urinary content of inositol phosphoglycans (IPGs), the IPG A-type and IPG P-type forms, which, among other actions, regulate pathways of glucose utilization, lipogenesis, triglyceride formation, and pyruvate dehydrogenase (PDH) activity. Urine samples from the entire diabetic group showed a 2- to 3-fold increase in IPG A-type, and a fall in the IPG P-type:IPG A-type ratio relative to the control group. Subdivision of the diabetic patients into lean IDDM and obese NIDDM groups revealed significant differences in the IPG P-type:IPG A-type ratio between these groups, this ratio decreasing with increases in the body mass index (BMI). Analysis of the relationships among IPGs and HbA1, blood pressure, and BMI indicated that a fall in the IPG P-type:IPG A-type ratio correlated with a rise in the HbA1 (indicative of impaired glycemic control), with increased systolic blood pressure and increased obesity, all factors linked to Syndrome X. There was a parallism between the profile of the IPG P-type:IPG A-type ratio and the well-established pattern of insulin resistance and BMI. In vitro studies of the effects of alterations in the IPG P-type:IPG A-type ratio on the activation of the pyruvate dehydrogenase complex (PDH complex) at the PDH phosphatase reaction demonstrated that IPG A-type forms antagonized the stimulation of the PDH phosphatase by IPG P-type forms, thus having a negative effect on the conversion of PDH to the active, dephosphorylated, form. This observation could provide a mechanism whereby the shifts in the IPG P-type:IPG A-type ratio reported above could change the metabolic pattern from one directed to glucose oxidation to one more directed toward energy conservation and lipid storage.

Adult↗

A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites.

BACKGROUND: An 18-nucleotide DNA oligomer, PS2.M, derived using an in vitro selection method was previously reported to bind hemin (Fe(III)-protoporphyrinIX) with submicromolar affinity. The DNA-hemin complex exhibited DNA-enhanced peroxidative activity. PS2. M is guanine-rich and requires potassium ions to fold to its active conformation, consistent with its forming a guanine-quaduplex. In investigating the specific catalytic features of PS2.M we tested the peroxidative properties of its RNA version (rPS2.M) as well as that of an unrelated DNA guanine-quadruplex, OXY4. RESULTS: The hemin-binding affinity of rPS2.M was found to be 30-fold weaker than that of PS2.M. The UV-visible spectra and kinetics of enzymatic peroxidation of the RNA-hemin complex, however, were nearly identical to those of its DNA counterpart. Both displayed peroxidase activity substantially greater than those of heme proteins such as catalase and Fe(III)-myoglobin. Kinetic analysis suggested that PS2. M and rPS2.M catalyzed the breakdown of the hemin-hydrogen peroxide covalent complex to products. The hemin complex of folded OXY4 (which bound hemin as strongly as did rPS2.M) had a distinct absorption spectrum and only a minor peroxidase activity above the background level. CONCLUSIONS: The results indicated that it is possible for RNA and DNA of the same sequence to fold to form comparable cofactor-binding sites, and to show comparable catalytic behavior. The results further suggest that only a subset of cofactor-binding sites formed within folded nucleic acids might be able to function as active sites, by providing the appropriate chemical environments for catalysis.

Base Sequence↗

Case report: Hepatocellular carcinoma in type 1a glycogen storage disease with identification of a glucose-6-phosphatase gene mutation in one family.

A 40-year-old man with glycogen storage disease type 1a (von Gierke disease, GSD1a) developed hepatocellular carcinoma (HCC). Cold single-strand conformation polymorphism (SSCP) with 12% glycerol identified the G727T mutation in the glucose-6-phosphatase (G6Pase) gene, which has been reported to be the most common mutation in Japanese GSD1a patients. This case report is the first documentation of HCC in a case with G727T mutation. Given the prevalence of HCC in GSD1a with various germline mutations, analysis is needed to confirm that the germline mutation in this case is really related to hepatocarcinogenesis. DNA analysis of the family pedigree of this case, revealed three individuals with GSD1a and seven heterozygous carriers of the G727T mutation. As the diagnosis of GSD1a in this family was made only after these three patients reached adulthood, DNA diagnosis may help early identification of GSD1a patients and prevention of the progression of the disease. This DNA-based diagnosis permits prenatal diagnosis in at-risk patients and may facilitate screening and counselling of patients clinically suspected of having this disease.

Adolescent↗

Endemic burkholderia cepacia bacteraemia: clinical features and antimicrobial susceptibilities of isolates.

Burkholderia cepacia has emerged as a nosocomial pathogen, causing numerous outbreaks, particularly among cystic fibrosis (CF) patients. Reports of clinical features of endemic B. cepacia bacteraemia in non-CF patients are rare. Twenty-five patients with B. cepacia bacteraemia were matched with 25 controls with nosocomial Escherichia coli bacteraemia at China Medical College Hospital, Taichung, Taiwan, over a period of 3 y. Case-patients included 16 men and 9 women, from 13 to 75 y. All had severe underlying diseases, most commonly malignancy (44%). Twenty-four patients (96%) had nosocomial infections. Five patients (20%) had polymicrobial bacteraemia. Our controls included 11 men and 14 women, age range 18-80 y. The most common underlying disease was malignancy (44%). Multivariate analysis revealed that indwelling central venous catheter was the significant risk factor predisposing to B. cepacia bacteraemia (p= 0.025). Eleven case-patients met the definition of catheter-related bloodstream infection. Fifteen patients (60%) received appropriate antimicrobial therapy after notification of positive blood cultures and susceptibility patterns. The overall case-fatality rate was 12% (3/25), only 1 of whom died of B. cepacia bacteraemia. There was no statistically significant difference in overall mortality rate between case-patients and controls. All isolates were susceptible to ceftazidime, piperacillin and minocycline and 84% of the isolates were susceptible to imipenem. B. cepacia should be considered a potential pathogen in hospitalized patients with severe underlying diseases, particularly those with indwelling central venous catheters.

Adolescent↗

Mxi1 mutations in human neurofibrosarcomas.

Mxi1 is thought to negatively regulate Myc function and may therefore be a potential tumor suppressor gene. Little effort has yet been made to find alterations involving this gene in human solid tumors. We screened 31 human gastric cancers, 7 esophageal cancers, 85 bone and soft tissue tumors of various types, including 4 neurofibrosarcomas. We also examined 29 human tumor cell lines consisting of 12 esophageal cancers, 7 glioma/glioblastomas and 10 others for Mxi1 mutations in exons 1, 2, 4 (HLH domain), 5 and 6. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and subsequent sequencing revealed three distinct polymorphisms in the intron-exon boundary upstream from exon 6. We discovered a missense mutation, GCA to GTA (Ala 54 Val), in exon 2 in a neurofibrosarcoma patient (case 1), two missense mutations, AAA to CAA (Lys 118 Gln) and GAA to GGA (Glu 154 Gly) in exon 5 of another neurofibrosarcoma patient (case 2), and 3 amino acid substitutions, GTG to GCG (Val 179 Ala), GTT to GCT (Val 181 Ala) and TTC to CTC (Phe 186 Leu), in a third neurofibrosarcoma patient (case 3). In case 3, loss of heterozygosity was also demonstrated by informative (TTC)3/(TTC)2 polymorphism. Our data demonstrate that mutations occur in the Mxi1 gene in neurofibrosarcoma. Missense mutations in the functional domain of Mxi1 in these cases may be involved in the pathogenesis of neurofibrosarcoma.

Adult↗

Effect of isoprenaline, carbachol, and Cs+ on Na+ activity and pacemaker potential in rabbit SA node cells.

Effects of isoprenaline, carbachol, and Cs+ on intracellular Na+ activity (a(i)Na) and spontaneous action potentials were studied in multicellular and single cell preparations isolated from rabbit sinoatrial (SA) nodes. a(i)Na was measured with double-barreled Na+-selective microelectrodes and the fluorescent Na+-indicator sodium-binding benzofuran isophthalate (SBFI). In spontaneously beating cells, aiNa measured with Na+-selective microelectrodes and SBFI were 4.5 +/- 1.2 mM (means +/- SD, n = 21) in multicellular preparations and 4.0 +/- 1.1 mM (n = 16) in single cells, respectively. Measurements of a(i)Na with microelectrodes showed that isoprenaline increased a(i)Na from 4.7 +/- 1.2 to 5.5 +/- 1.6 mM (n = 16, P < 0.01) and shortened the action potential cycle length (ACL) from 338 +/- 46 to 269 +/- 35 ms (n = 16, P < 0.01). However, increasing the action potential rate by pacing produced a much smaller increase in a(i)Na. Changes in a(i)Na and ACL produced by isoprenaline were blocked by Cs+. The selective hyperpolarization-activated inward current (If) blocker ZD-7288 decreased a(i)Na from 5.2 +/- 1.0 to 4.6 +/- 1.3 mM (n = 4, P < 0.01) and prolonged ACL from 394 +/- 20 to 553 +/- 68 ms (n = 4, P < 0.01). The If blocker substantially inhibited the increase in a(i)Na produced by isoprenaline. Carbachol and Cs+ decreased aiNa from 4.6 +/- 1.4 to 3.9 +/- 1.2 mM (n = 15, P < 0.01) and from 4.9 +/- 1.0 to 3.9 +/- 1.3 mM (n = 18, P < 0.01), respectively. In addition, carbachol and Cs+ prolonged ACL from 345 +/- 44 to 587 +/- 100 ms (n = 15, P < 0.01) and from 353 +/- 30 to 464 +/- 87 ms (n = 18, P < 0.01), respectively. However, carbachol and Cs+ almost did not change a(i)Na when SA node cells became quiescent in a 25.4 mM extracellular K+ concentration. The results suggest that isoprenaline, ZD-7288, carbachol, or Cs+ might have changed a(i)Na and action potential rate by possibly stimulating or inhibiting If carried by Na+. Measurements of a(i)Na with SBFI showed that isoprenaline, carbachol, and Cs+ produced a(i)Na changes that were similar to those measured with the microelectrodes.

Action Potentials↗

Rheologic determinant changes of erythrocytes in Binswanger's disease.

BACKGROUND: Binswanger's disease (BD) has been associated with severe arteriosclerotic changes in the long perforating arteries and with impaired cerebrovascular responsiveness to hypercapnia. Rheology parameters may become important factors in regulating cerebral blood flow. The purpose of this study was to investigate the changes in rheologic determinants of erythrocytes and to discuss the relation of erythrocytes and white matter lesions in this type of dementia. METHODS: Twenty-eight patients suffering from BD and a control group matched for age, sex and cerebrovascular risk factors were tested for the following hemorheologic variables: erythrocyte deformability, erythrocyte membrane fluidity, erythrocyte aggregation, plasma viscosity and whole blood viscosity. Additionally, red cell membrane metabolic parameters, lipids and individual membrane phospholipids, sialic acid (SA) and malondialdehyde (MDA) contents, and ATPase activities were measured. RESULTS: A significant decrease in erythrocyte deformability, erythrocyte membrane fluidity, membrane phosphatidylethanolamine, membrane phosphatidylcholine, membrane SA and membrane ATPase activities, and a significant increase in membrane cholesterol, cholesterol to total phospholipid ratio, MDA, broad viscosity and erythrocyte aggregation were observed in BD patients when compared with those of the matched control group. CONCLUSIONS: Changes in erythrocyte membrane parameters, especially in phospholipids, can produce serious metabolic disorders and influence the rheologic properties of erythrocytes in patients with BD. These alterations can contribute to a circulatory slowdown and may lead to worsening of the condition of the cerebral white matter in these patients.

Adenosine Triphosphatases↗

The significance and technical aspects of quantitative measurements of inflammatory mediators in allergic rhinitis.

The pathophysiology of allergic rhinitis induced by various inhalant allergens through an IgE mediated mechanism, has been well demonstrated. The participation of many important inflammatory cells and mediators released by these cells in the human nasal allergic reaction provides insight into the relationship between the responsiveness to allergen exposure and nasal symptoms of allergic rhinitis. This paper summarizes our previous studies on some important mediators in the nasal secretions of atopic patients during different phases after nasal allergen challenge and during natural allergen exposure. The microsuction technique proves to be an especially useful and reliable nasal sampling method permitting quantitative analysis of important mediators such as histamine, tryptase, leukotriene C4 and eosinophil cationic protein in nasal secretions. The measurement of these mediators during allergic reactions provides accurate data on the activity of some important inflammatory cells (i.e., mast cells, basophils, and eosinophils) and their responses to therapy.

Allergens↗

Interaction of EphB2-tyrosine kinase receptor and its ligand conveys dorsalization signal in Xenopus laevis development.

The Eph class is the largest family of receptor tyrosine kinases and has been shown to play various roles in neural development including axon pathfinding and neural crest migration. EphB2 associates with transmembrane ligands Ephrin-B1 and -B2, which leads to tyrosine phosphorylation of both the ligands and receptor and is presumed to regulate cell-to-cell interactions by bidirectional signaling. We have investigated the biological effects of the EphB2-induced signal in the early stage of Xenopus laevis development. Xenopus EphB2 transcripts were detected maternally and were expressed at equal levels between the ventral and dorsal halves of the gastrulae, with expression increasing after the late gastrula stage. EphB2 mRNA expression in dorsal marginal zone explants from gastrulae increases during later development while that in ventral explants does not. We show here that microinjection of RNA encoding EphB2 into a ventral blastomere of embryos induced a partial secondary dorsal axis which consisted of neural tissues, notochord and somites. Analysis with molecular markers verified that the microinjected EphB2 dorsalized the mesoderm of ventral marginal zone explants. These dorsalizing effects of EphB2 in both the whole embryo and ventral explants were inhibited by the coinjection of RNA encoding the soluble form of Ephrin-B1. Furthermore, co-injection of EphB2 and Ephrin-B1 RNAs synergistically enhanced the dorsalization effect. These data show that the interaction between EphB2 and its ligands including Ephrin-B1 causes signaling events which lead to dorsal development, and strongly suggests the existence of proteins which mediate the dorsalization induced by EphB2 in early stage embryos of Xenopus laevis.

Amino Acid Sequence↗

Drug-attributed anaphylaxis.

Allergic type I reactions to medicines range in their clinical presentation from rhinitis and urticaria to severe bronchoconstriction and anaphylactic shock. We examined all cases of suspected drug induced reactions classified as anaphylactic reactions or shock reported in Sweden between 1972 and 1995 with regard to patient characteristics and drug(s) suspected. Some comparisons with drug sales and prescription data were also made. During the study period of a total of 1338 reports concerned anaphylactic/oid shock or reactions with at least a possible causal relation to medicine giving an overall reporting rate of seven cases per million inhabitants per year of drug-induced anaphylaxis. Of these 1338 patients 51 (3.8%) died from their reactions. Among the non-fatal cases, 460 (34.4%) were diagnosed as shock and 827 (61.8%) as anaphylactic reactions. In total 46.3% of all reports concerned men but men were over-represented among the older patients and among the fatal cases (65%). There were 201 different drugs reported as 'suspected' them most common of which were dextrans (418 reports), X-ray contrast media (161 reports) and antibiotics (153 reports). For dextrans the rate of anaphylactic reactions, shock and fatal cases reported were 128,101 and 21 per million bottles respectively. This decreased to 10.3, 9.8, and 0.4 per million bottles after the introduction of preventive treatment with dextran 1 in 1983.The reporting rate for ionic contrast media were 0.14, 0.13 and 0.02 per 1000 l for reactions, shock and fatal cases respectively whilst for non-ionic contrast media they were 0.7/1000 l for reactions, 0.02/1000 l for shock, but there was no report of a fatal case. For phenoxymethylpenicillin the reported rate of anaphylaxis was 0.14 cases per million defined daily doses and for benzylpenicillin it was 3.7 cases per million defined daily doses. During the study period several drugs have been identified as important causes of anaphylaxis and measures have been taken to decrease the risk of anaphylaxis e.g. the introduction of preventive treatment with dextran 1, the shift from ionic to non-ionic contrast media and the abolition of polyethoxylated castor oil as a solvent. Spontaneous reporting of drug-induced anaphylaxis remains an important surveillance model but needs to be complemented by better quantitative methods.

Journal Article↗

Antibodies to heat-shock protein 27 are associated with improved survival in patients with breast cancer.

The overexpression of the heat-shock proteins hsp90, hsp70 and hsp27 in human mammary carcinomas has previously been shown to correlate with reduced overall survival. Moreover, antibodies to hsp90 were detectable in the serum of a large proportion of breast cancer patients but they were not found in normal controls. High antibody levels also correlated with reduced survival. Here, we show that antibodies to hsp27 were also detectable in the sera from breast cancer patients but not from normal controls, whereas antibodies to hsp70 were detectable in approximately one-third of both groups. The presence of antibodies to hsp27 was correlated with an improved rather than a reduced survival, particularly beyond the first 5 years. Hence, the overexpression of hsps in breast cancer cells does not provoke a generalized immune response to all the hsps. Moreover, the presence of antibodies to different hsps has distinct associations with survival. These effects are discussed in terms of the mechanisms that provoke an immune response to the hsps and the protective/non-protective effects of such a response.

Antibodies↗

Analyses of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer.

Mutations in the transforming growth factor beta type II receptor (TGFbetaRII) gene have been detected in several human cancer types exhibiting microsatellite instability. Using intron primers previously reported for examination of the entire coding region of the TGFbetaRII gene, 29 sporadic gastric cancers were screened with non-radioactive single strand conformation polymorphism and subsequent DNA sequencing analysis. Mutations of the TGFbetaRII gene were detected in three out of 29 tumors (10%). Two cases showed deletions in a polyadenine tract in both alleles and was positively associated with replication error. One case had an insertion of GA dinucleotide sequence in one allele. Mutations of the TGFbetaRII gene were restricted to exon 3 and other coding regions were not affected. Loss of heterozygosity was detected by analyzing a polymorphic site in intron 2. Three out of nine (33%) informative cases, which were all of intestinal type and advanced cases, showed loss of heterozygosity but neither TGFbetaRII mutation nor replication error was found in these cases. Immunoreactivity of TGFbetaRII in tumor tissues was reduced to a different extent in the gastric cancer with genetically abnormal transforming growth factor. Although the numbers studied are small, homozygous (A)10 deletion or loss of heterozygosity of TGFbetaRII is involved in tumorigenesis and progression of at least some part of sporadic gastric cancer.

Humans↗

Mutational analyses of multiple target genes in histologically heterogeneous gastric cancer with microsatellite instability.

It has been recognized that gastric cancer often shows histological heterogeneity in a single tumor. Although microsatellite instability (MSI) has been reported in gastric cancer, the significance of genomic instability in gastric cancers with histological heterogeneity within a single tumor has never been addressed. We investigated MSI at 8 microsatellite loci in 40 normal/tumor DNA pairs from 20 gastric cancers with histological heterogeneity. Six of 20 patients (10 DNAs of 40 tumor DNAs) had severe MSI in more than 3 loci. Four of the MSI-positive cases had frameshift mutations in the poly(A)10 tract of the TGF beta RII gene. This mutation was found only in the MSI-positive component in the 2 cases (cases 4 and 5) in which only 1 component exhibited MSI. The other 4 cases demonstrated homozygous or heteroclonal mutations (1 and 2 base deletions) in the poly(A)8 tract of the hMSH3 gene; no mutation was detected in the poly(C)8 tract of the hMSH6 gene in any of the MSI-positive cases. The profile of alterations in multiple targets was different between the 2 components in most of the cases (5/6). These findings suggest that mismatch repair deficiency in MSI-positive tumors causes multiple gene inactivations through frameshift mutations in short repetitive sequences in a heterogeneous way within a histologically heterogeneous tumor.

Aged↗

Serratia marcescens bacteremia: clinical features and antimicrobial susceptibilities of the isolates.

From July 1996 to June 1997, 22 adult patients with Serratia marcescens bacteremia were retrospectively studied at China Medical College Hospital. All patients had severe underlying disease, most commonly diabetes mellitus. Eighteen (82%) patients had nosocomial infection. Clinical syndromes included primary bacteremia (68%), pneumonia (14%), urinary tract infection (9%), suppurative thrombophlebitis (5%) and surgical wound infection (5%). Twelve patients had central venous catheters in place at the onset of bacteremia, but only one case met the definition of catheter-related infection. In 14 (64%) patients, portal of entry of S. marcescens infection was unknown. Five (23%) patients had concurrent polymicrobial bacteremia. The overall mortality rate was 50% (11/22). Seven (32%) of the 22 patients died of S. marcescens bacteremia. All isolates were resistant to ampicillin and cephalothin and susceptible to imipenem. Ninety-five percent of strains were susceptible to moxalactam, 68% to amikacin, 55% to ceftazidime, 45% to aztreonam, 32% to ceftriaxone, 27% to gentamicin, 18% to cefoperazone and cefotaxime, and 9% to piperacillin. MICs of various antibiotics demonstrated that ciprofloxacin and imipenem had good activities against S. marcescens, with MIC90 of 0.19 microg/mL and 1.0 microg/mL, respectively. Due to increasing multidrug resistance, choosing appropriate antimicrobial agents such as moxalactam, imipenem, and ciprofloxacin should be highly recommended for the treatment of S. marcescens infections.

Adolescent↗

Clinical and microbiologic characteristics of Ochrobactrum anthropi bacteremia.

Ochrobactrum anthropi is an oxidase-positive, nonfermenting, gram-negative bacillus that is an emerging pathogen in immunocompromised patients, particularly in those with indwelling central venous catheters. Reports of clinical manifestation of O. anthropi bacteremia are rare. Herein, we report the clinical and microbiologic characteristics of O. anthropi bacteremia in 15 patients. There were eight males and seven females, whose ages ranged from 1 month to 84 years (mean, 34 years). Ten infections were community acquired. All patients had severe underlying disease and manifested primary O. anthropi bacteremia with no obvious focus. Only three patients had central venous catheters in place at the onset of bacteremia, but none of these showed evidence of catheter-related infection. The mean duration of fever was 4 days (range 0-11) and the mean white blood cell count was 13 x 10(9)/L (range 5.5-28 x 10(9)). All O. anthropi isolates tested were resistant to ampicillin, cephalothin, cefonicid, amoxicillin/clavulanic acid, piperacillin, aztreonam, and ceftazidime, and all were susceptible to gentamicin, amikacin, imipenem, ceftriaxone, and cefoperazone. Most were also susceptible to cefotaxime and moxalactam. Monotherapy with an aminoglycoside or an appropriate beta-lactam (such as cefotaxime or ceftriaxone) yielded good clinical response. None of the 15 patients died directly from O. anthropi bacteremia. Our findings indicate that O. anthropi is often community acquired and can be pathogenic in critically ill or immunocompromised patients with or without indwelling catheters. Although O. anthropi can produce clinically significant infections, the organism seems to be of relatively low virulence.

Adolescent↗