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H Yang

Publications and source records attributed to H Yang.

At least 289 records · Page 16Linked to original sources
PubMed2000

Candidate locus for a nuclear modifier gene for maternally inherited deafness.

Maternally inherited deafness associated with the A1555G mutation in the mitochondrial 12S ribosomal RNA (rRNA) gene appears to require additional environmental or genetic changes for phenotypic expression. Aminoglycosides have been identified as one such environmental factor. In one large Arab-Israeli pedigree with congenital hearing loss in some of the family members with the A1555G mutation and with no exposure to aminoglycosides, biochemical evidence has suggested the role of nuclear modifier gene(s), but a genomewide search has indicated the absence of a single major locus having such an effect. Thus it has been concluded that the penetrance of the mitochondrial mutation appears to depend on additive effects of several nuclear genes. We have now investigated 10 multiplex Spanish and Italian families with 35 members with the A1555G mutation and sensorineural deafness. Parametric analysis of a genomewide screen again failed to identify significant evidence for linkage to a single autosomal locus. However, nonparametric analysis supported the role of the chromosomal region around marker D8S277. The combined maximized allele-sharing LOD score of 3.1 in Arab-Israeli/Spanish/Italian families represents a highly suggestive linkage result. We suggest that this region should be considered a candidate for containing the first human nuclear modifier gene for a mitochondrial DNA disorder. The locus operates in Arab-Israeli, Spanish, and Italian families, resulting in the deafness phenotype on a background of the mitochondrial A1555G mutation. No obvious candidate genes are located in this region.

Arabs↗
PubMed2000

Defective cleavage of membrane bound TGFalpha leads to enhanced activation of the EGF receptor in malignant cells.

Transforming growth factor alpha (TGFalpha) is widely expressed in malignant as well as normal cells and is involved in regulating cell growth and differentiation. Although processing of TGFalpha has been extensively studied in normal cells, there is little information regarding TGFalpha cleavage in malignant cells. Therefore, we compared the processing of TGFalpha in two human colon carcinoma cell lines. We found that there was a defective cleavage pattern for the TGFalpha precursor resulting in retention of partially processed TGFalpha on the cell surface of both the HCT116a2alphaS3 and CBS4alphaS2 cell lines. This raised the possibility that signaling from the resulting defective cleavage species could differ from that of soluble TGFalpha. The membrane-associated TGFalpha induced higher phosphorylation of EGFR on the cell surface of adjacent cells than equivalent levels of mature TGFalpha. The interaction of membrane bound TGFalpha precursor with the EGFR caused a slower internalization of activated EGFR relative to the internalization of the soluble TGFalpha/EGFR complexes. In addition, the tethered TGFalpha was resistant to the ability of protein-tyrosine phosphatases (PTPs) to reduce EGFR tyrosine phosphorylation, also contributing to higher activation of EGFR. The enhanced activation of EGFR by the tethered form of TGFalpha was reflected by higher activation of Grb2, SHC and Erk downstream mediators of EGF receptor signaling. The higher activation of EGFR by membrane tethered TGFalpha indicates that defective TGFalpha processing provides a mechanism whereby malignant cells can obtain a growth advantage over normal cells.

Cell Membrane↗
PubMed2000

Anti-LFA-1 therapy induces long-term islet allograft acceptance in the absence of IFN-gamma or IL-4.

mAb therapy directed against a variety of cell surface accessory molecules has been effectively utilized to prolong allograft acceptance in various models of tissue and organ transplantation. The purpose of this study was to determine whether transient therapy directed against the adhesion molecule LFA-1 (CD11a) was sufficient to induce donor-specific tolerance to pancreatic islet allografts. Anti-LFA-1 monotherapy was found to be efficacious in inducing long-term islet allograft acceptance in multiple donor-recipient strain combinations. Graft acceptance following anti-LFA-1 therapy was not simply due to clonal ignorance of donor Ags in that the majority of recipients bearing established islet allografts resisted rejection induced by immunization with donor-type APCs. Furthermore, donor-specific tolerance from anti-LFA-1-treated animals could be transferred to secondary immune-deficient animals. Taken together, these results indicated that transient anti-LFA-1 monotherapy resulted in donor-specific tolerance. In vitro, functionally tolerant animals retained normal anti-donor reactivity as assessed by proliferative, cytotoxic, and cytokine release assays that demonstrated that tolerance was not secondary to general clonal deletion or anergy of donor-reactive T cells. Finally, anti-LFA-1 treatment was effective in both IL-4-deficient and IFN-gamma-deficient recipients, indicating that neither of these cytokines are universally required for allograft acceptance. These results suggest that anti-adhesion-based therapy can induce a nondeletional form of tolerance that is not overtly dependent on the prototypic Th1 and Th2 cytokines, IFN-gamma and IL-4, respectively, in contrast to results in other transplantation models.

Adoptive Transfer↗
PubMed2000

Existence of a plant tyrosylprotein sulfotransferase: novel plant enzyme catalyzing tyrosine O-sulfation of preprophytosulfokine variants in vitro.

An in vitro assay system to detect tyrosylprotein sulfotransferase (TPST) activity of higher plant cells was established, using synthetic oligopeptides based on the deduced amino acid sequence of a phytosulfokine-alpha (PSK-alpha) precursor. TPST activity was found in microsomal membrane fractions of rice, asparagus and carrot cells and it was confirmed that acidic amino acid residues adjacent to the tyrosine residues of acceptor peptides were essential to the sulfation reaction. The asparagus TPST exhibited a broad pH optimum of 7.0-8.5, required manganese ions for maximal activity and appeared to be a membrane-bound protein localized in the Golgi apparatus. These enzymes should be defined as a new class of plant sulfotransferases that catalyze tyrosine O-sulfation of a PSK-alpha precursor and other unknown proteins.

Amino Acid Sequence↗
PubMed2000

Cloning and characterization of a new member of the Nudix hydrolases from human and mouse.

Proteins containing the Nudix box "GX(5)EX(7)REUXEEXGU" (where U is usually Leu, Val, or Ile) are Nudix hydrolases, which catalyze the hydrolysis of a variety of nucleoside diphosphate derivatives. Here we report cloning and characterization of a human cDNA encoding a novel nudix hydrolase NUDT5 for the hydrolysis of ADP-sugars. The deduced amino acid sequence of NUDT5 contains 219 amino acids, including a conserved Nudix box sequence. The recombinant NUDT5 was expressed in Escherichia coli and purified to near homogeneity. At the optimal pH of 7, the purified recombinant NUDT5 catalyzed hydrolysis of two major substrates ADP-ribose and ADP-mannose with K(m) values of 32 and 83 microM, respectively; the V(max) for ADP-mannose was about 1.5 times that with ADP-ribose. The murine NUDT5 homolog was also cloned and characterized. mNudT5 has 81% amino acid identity to NUDT5 with catalytic activities similar to NUDT5 under the optimal pH of 9. Both NUDT5 and mNudT5 transcripts were ubiquitously expressed in tissues analyzed with preferential abundance in liver. The genomic structures of both NUDT5 and mNudT5 were determined and located on human chromosome 10 and mouse chromosome 2, respectively. The role of NUDT5 in maintaining levels of free ADP-ribose in cells is discussed.

Adenosine Diphosphate Ribose↗
PubMed2000

Glucose starvation reduces IGF-I mRNA in tumor cells: evidence for an effect on mRNA stability.

The purpose of this study was to characterize the mechanisms by which glucose regulates IGF-I gene expression in rat C6 glioma cells and in rat GH3 pituitary adenoma cells. Glucose starvation for periods of 12 to 48 h decreased IGF-I mRNA levels. In contrast, there was no stimulation of IGF-I mRNA by medium glucose between 1 and 25 mM over a 24-h period. Studies with hexoses and glycolytic metabolites suggested that glucose metabolism was required to maintain IGF-I mRNA. Glucose starvation lowered IGF-I mRNA half-life in both C6 and GH3 cells. Protein synthesis inhibition lowered IGF-I mRNA by about 20% in glucose-fed C6 and GH3 cells, while potently increasing IGF-I mRNA in glucose-starved C6 cells and not altering IGF-I mRNA in glucose-starved GH3 cells. Our results suggest that in these tumor cells, IGF-I mRNA stability is reduced by glucose starvation, secondary to a deficiency in intracellular glucose metabolism. Ongoing protein synthesis is not required for this mRNA de-stabilizing effect in GH3 cells. Rather, in glucose-starved C6 cells, decreased IGF-I mRNA stability may result from the action of a labile protein.

Animals↗
PubMed2000

Cloning and functional characterization of the 5'-flanking region of human methionine adenosyltransferase 1A gene.

Methionine adenosyltransferase (MAT) is an essential cellular enzyme which catalyses the formation of S-adenosylmethionine, the principal methyl donor and precursor for polyamines. In mammals, two different genes, MAT1A and MAT2A, encode for liver-specific and non-liver-specific MAT respectively. We previously described a switch in the MAT expression from MAT1A to MAT2A in human liver cancer, which offered the cancerous cell a growth advantage. Loss of MAT1A expression was due to lack of gene transcription. To study regulation of the MAT1A gene, we have cloned and characterized a 1.9 kb 5'-flanking region of the human MAT1A gene. One transcriptional start site, located 25 nt downstream from a consensus TATA box, was identified by primer extension and RNase protection assays. The promoter contains several consensus binding sites for CAAT enhancer binding protein (C/EBP) and hepatocyte-enriched nuclear factor (HNF), transcriptional factors important in liver-specific gene expression. The human MAT1A promoter was able to efficiently drive luciferase expression in Chang cells, a human liver cell line, but not in HeLa cells. Sequential deletion analysis of the promoter revealed two DNA regions upstream of the translational start site, -705 to -839 bp and -1111 to -1483 bp, which are involved in positive and negative gene regulation, respectively. Specific protein binding to these regions was confirmed by electrophoretic-mobility-shift and DNase I footprinting assays. Similar to the situation with the rat MAT1A, glucocorticoid treatment also increased human MAT1A expression and promoter activity in a dose- and time-dependent manner.

5' Untranslated Regions↗
PubMed2000

MSY2: a slowly evolving minisatellite on the human Y chromosome which provides a useful polymorphic marker in Chinese populations.

We present the second human Y-specific minisatellite, MSY2 (DYS440). It consists of three or four copies of a 99-110bp repeat unit and is located about 1kb upstream of the DBY gene. The most common allele contains four units, but a three-unit allele has arisen on at least four occasions; in chimpanzees and orangutans, MSY2 contains only two units. It is therefore evolving slowly and provides a particularly useful polymorphic marker for Chinese populations.

Alleles↗
PubMed2000

Bootstrap confidence intervals for the sensitivity of a quantitative diagnostic test.

We examine bootstrap approaches to the analysis of the sensitivity of quantitative diagnostic test data. Methods exist for inference concerning the sensitivity of one or more tests for fixed levels of specificity, taking into account the variability in the sensitivity due to variability in the test values for normal subjects. However, parametric methods do not adequately account for error, particularly when the data are non-normally distributed, and non-parametric methods have low power. We implement bootstrap methods for confidence limits for the sensitivity of a test for a fixed specificity and demonstrate that under certain circumstances the bootstrap method gives more accurate confidence intervals than do other methods, while it performs at least as well as other methods in many standard situations.

Algorithms↗
PubMed2000

Intracisternal PYY inhibits gastric lesions induced by ethanol in rats: role of PYY-preferring receptors?

We previously reported that intracisternal (i.c.) injection of peptide YY (PYY) and low doses of thyrotropin-releasing hormone (TRH) or TRH analog, RX 77368, increased the resistance of the gastric mucosa to ethanol injury through vagal pathways in rats. The gastroprotective effect of i.c. injection of PYY/neuropeptide NPY (NPY) agonists with differential in vitro affinity to the Y receptor subtypes was examined in urethane-anesthetized rats. Intragastric administration of ethanol (45%, 5 ml/kg) results in mucosal lesions covering 23+/-2% of the gastric corpus in 1 h. PYY (500 ng, i.c.) significantly reduced ethanol-induced gastric lesions by 52%. [Pro34]PYY (PYY-preferring/Y1/Y5/Y4 subtypes) injected i.c. at 50, 100, 200 or 500 ng, reduced dose dependently gastric lesions to 15.4+/-2.2%, 11.4+/-3.1%, 8.6+/-2.9% and 5.4+/-2.2%, respectively. PYY3-36, (Y2/Y4 subtypes), [Leu31, Pro34]NPY (Y1/Y5), NPY (Y3/Y1/Y5/Y2) and pancreatic polypeptide (PP, Y4) injected i.c. at 500 ng did not influence significantly ethanol-induced gastric lesions. Combined i.c. injection of RX 77368 (1 ng) and Pro34PYY (25 ng), at sub-threshold doses given singly, reduced ethanol-induced gastric injury to 12.9+/-2.3% while RX 77368 (1 ng) plus PYY3-36 (500 ng) or [Leu31, Pro34]NPY (25 ng) had no effect. These findings indicate that i.c. PYY-induced gastric protection against 45% ethanol is mediated by a Y receptor subtype which bears similarity with the putative PYY-preferring receptor and distinct from the currently defined Y1/Y5; in addition, there is a synergistic interaction between activation of this PYY-preferring receptor and i.c. TRH to increase the resistance of the gastric mucosa to injury caused by 45% ethanol.

Animals↗
PubMed2000

In vitro evaluation of hepatitis B virus polymerase mutations associated with famciclovir resistance.

Several mutations (V521L, P525L, L528M, T532S, and V555I) in the gene for hepatitis B virus (HBV) polymerase have been identified in HBV isolated from patients that displayed break-through viremia during famciclovir treatment. To determine whether these mutations cause phenotypic resistance to famciclovir, we compared the inhibition constants (K(i)) of penciclovir triphosphate (PCVTP, the active metabolite of famciclovir) for recombinant wild-type and mutant HBV polymerases containing these mutations. In in vitro enzymatic assays, the V555I mutation displayed the most resistance (with K(i) increased by 6.2-fold) to PCVTP. The V521L and L528M mutations showed moderately decreased sensitivity to PCVTP (K(i) increased by >3-fold). We also analyzed the cross-resistance profiles of these variants for adefovir and lamivudine, two other antiviral agents that also inhibit DNA replication by HBV polymerase. All 5 famciclovir-associated mutations were sensitive to adefovir diphosphate (ADVDP) in in vitro enzymatic assays (<2.3-fold decreased sensitivity). The V521L, L528M, and T532S mutations were also sensitive to lamivudine triphosphate (LAMTP); however, the P525L and V555I mutations displayed moderately decreased sensitivity to LAMTP in enzymatic assays (3.6-fold decreased sensitivity). The lamivudine-resistant mutations M552I, M552V, and L528M+M552V, which were previously shown to display 8- to 25-fold resistance to LAMTP, were less resistant (< or = 3.1-fold) to PCVTP.

2-Aminopurine↗
PubMed2000

Cryobiology of articular cartilage: ice morphology and recovery of chondrocytes.

The cryopreservation of articular cartilage chondrocytes has been achieved with cells isolated from the cartilage matrix but has found only limited success when the tissue is left intact. Previous work with ovine cartilage has shown that cryopreservation of the chondrocytes of the superficial and deep zones is possible, but the cells of the intermediate zone have not been successfully cryopreserved. This finding led to the suggestion that there might be biological differences between chondrocytes of the different morphological zones that were responsible for this differential recovery. This study investigates the hypothesis that the cells of the intermediate zone are more sensitive to cryoinjury by introducing cuts in the cartilage so that cells of the intermediate zone have the same proximity to the outer surface of the tissue as the cells of the superficial zone. When this was done, it was found that cells of the intermediate zone could survive cryopreservation as well as the cells of the superficial zone when they were near a surface, but not when they were embedded deep within the tissue. Thus the hypothesis of a biological difference between the cells of the two zones being responsible for the differential recovery is disproved. It is further hypothesized that physical proximity to a surface leads to higher recovery as a result of planar ice growth into the cartilage.

Animals↗
PubMed2000

Analysis of anesthesia physician resources: projected Ontario deficit in 2005.

PURPOSE: To clarify the recent perception of shortfalls in anesthesia physician resources, two models were used to assess these resources in Ontario, Canada. METHODS: Two models, demand-based and benchmarking, were used. In the demand-based model estimated future supply and attrition were obtained from information on Ontario Ministry of Health funded trainees. Data from the Canadian Residents Matching Service and the Association of Canadian University Departments of Anesthesia were also used. Current demand was identified from a telephone survey of Departments of Anesthesia in ten Ontario cities. The number of anesthesia practitioners in Ontario was estimated from the 1996 Canadian Anesthesiologists' Society Physician Resource Database (CASPRD) in the demand-based model. In the benchmarking model, using Alberta as the closest published analogue to Ontario, the annual specialist growth rate in Ontario since 1986 was calculated in the literature as 2.8%/yr for 1986-1994. The number of anesthesiologists in Ontario from the 1986 CASPRD was used to calculate need based on that growth rate. Results are compared with population to anesthesiologist (P/A) ratios calculated from Statistics Canada population data and physician numbers from CASPRD. RESULTS: A shortfall in the number of anesthesiologists has been identified. The P/A ratio worsened by 17.6% from 1986 to 1996. The demand-based model indicated that the shortfall is increased from a current deficit of 40 to 68 by 2005, using CASPRD. Benchmarking showed that the estimated shortfall in 1994 was 131. CONCLUSION: This conservative approach indicates that the shortfall in anesthesiologist physician resources will worsen by 2005.

Adult↗
PubMed2000

Reversal of paraparesis after thoracic aneurysm repair by cerebrospinal fluid drainage.

PURPOSE: To describe a case of reversal of delayed paraparesis, after an elective type I thoracoabdominal aortic aneurysm (TAAA) repair, via cerebrospinal fluid (CSF) drainage. CLINICAL FEATURES: A 75-yr-old woman developed paraparesis 13 hr after type I TAAA repair. The patient had been given combined regional and general anesthesia. There was no cerebrospinal fluid drain inserted at the time of surgery. The patient was hemodynamically stable throughout the procedure and was transported to the intensive care unit with trachea intubated and lungs ventilated. She demonstrated some initial lower limb paraparesis but had good recovery of limb function three hours after cessation of the epidural infusion. However, five hours and forty-five minutes after stopping the epidural, she was again paraparetic. Peripheral nerve injury, prolonged effects of epidural local anesthetic, and epidural hematoma were ruled out as precipitating factors. Cord ischemia was considered possible and a CSF catheter was inserted. Immediate improvement was seen upon catheter insertion and commencement of drainage, beginning with movement in the left toes and foot. Drainage was performed when the CFS pressure became > 15 mmHg. Motor function in the lower limbs continued to improve with each drainage extending to complete recovery after 40 hr. She was discharged home 11 days after surgery with no neurological deficit. CONCLUSION: Drainage of CSF was useful in treating a case of post-TAAA neurologic deficit.

Aged↗
PubMed2000

Bidirectional supply of glutamine maintains enterocyte ATP content in the in vitro using chamber model.

Glutamine is the principal energy source for enterocytes, but it is not known whether parenteral or enteral supplementation is most beneficial to gut integrity. The aim of this study was to evaluate the effects of glutamine in uni- or bidirectional supply on the viability of intestinal mucosa of starved rats during incubation in Ussing chambers. Segments of jejunum from rats starved for 48 h were randomly mounted in Ussing chambers with three nutrient solutions: Krebs buffer without glutamine; 6 mM glutamine added to the mucosal side; 6 mM glutamine added to the mucosal side and 0.6 mM glutamine to the serosal side. ATP content of the mucosa, electrophysiology, and 51Cr-ethylenediaminetetraacetate (EDTA) permeability were studied during 180 min of incubation. The addition of glutamine to both sides of the stripped mucosa improved ATP levels compared to the Krebs solution (P < 0.05), and the addition of glutamine resulted in an increase in short circuit current (P < 0.05). No significant differences were seen in 51Cr-EDTA permeability or epithelial electrical resistance. Glutamine supplementation to both the luminal and serosal side in the Ussing chamber was more effective than luminal glutamine only in maintaining ATP levels of intestinal mucosa. Bidirectional supplementation of glutamine might improve intestinal energy metabolism and viability in in vitro studies.

Adenosine Triphosphate↗
PubMed2000

Determinants of unexplained antepartum fetal deaths.

OBJECTIVE: To assess fetal, maternal, and pregnancy-related determinants of unexplained antepartum fetal death. METHODS: We conducted a hospital-based cohort study of 84,294 births weighing 500 g or more from 1961-1974 and 1978-1996. Unexplained fetal deaths were defined as fetal deaths occurring before labor without evidence of significant fetal, maternal, or placental pathology. RESULTS: One hundred ninety-six unexplained antepartum fetal deaths accounted for 27.2% of 721 total fetal deaths. Two thirds of the unexplained fetal deaths occurred after 35 weeks' gestation. The following factors were independently associated with unexplained fetal death: maternal prepregnancy weight greater than 68 kg (adjusted odds ratio [OR] 2.9; 95% confidence interval [CI] 1.85, 4.68), birth weight ratio (defined as ratio of birth weight to mean weight for gestational age) between 0.75 and 0.85 (OR 2.77; 95% CI 1.48, 5.18) or over 1.15 (OR 2.36; 95% CI 1.26, 4.44), fewer than four antenatal visits in women whose fetuses died at 37 weeks or later (OR 2.21; 95% CI 1.08, 4.52), primiparity (OR 1.74; 95% CI 1.26, 2.40), parity of three or more (OR 2.01; 95% CI 1.26, 3.20), low socioeconomic status (OR 1.59; 95% CI 1.14, 2.22), cord loops (OR 1.75; 95% CI 1.04, 2.97) and, for the 1978-1996 period only, maternal age 40 years or more (OR 3.69; 95% CI 1.28, 10.58). Trimester of first antenatal visit, low maternal weight, postdate pregnancy, fetal-to-placental weight ratio, fetal sex, previous fetal death, previous abortion, cigarette smoking, and alcohol use were not significantly associated with unexplained fetal death. CONCLUSION: In this study, we identified several factors associated with an increased risk of unexplained fetal death.

Adult↗
PubMed2000

Improved postprandial glycemic control with Humalog Mix75/25 after a standard test meal in patients with type 2 diabetes mellitus.

OBJECTIVE: This double-blind study was designed to compare the postprandial glucodynamic profile of Humalog Mix75/25, a new premixed insulin analogue containing 75% neutral protamine lispro and 25% insulin lispro with that of human insulin 70/30 (70% neutral protamine Hagedorn insulin and 30% regular human insulin) in patients with type 2 diabetes mellitus. BACKGROUND: Insulin lispro Mix75/25 (Mix75/25) is the first available insulin formulation in which both the rapid-acting and basal components are insulin analogues. METHODS: This randomized, multicenter, double-blind, crossover study monitored patients' postprandial glucodynamic response to Mix75/25 and human insulin 70/30 (70/30) after a standard test meal. Eighty-four patients with type 2 diabetes participated in this study and were randomly assigned to 1 of 2 treatment sequence groups. Patients received an identical test meal on 4 occasions, completing 2 test meals for each treatment. Equal doses of Mix75/25 or 70/30 were administered 5 minutes before each of the 2 test meals, with doses individualized for each patient. Blood samples were collected for 4 hours after the meal for measurement of plasma glucose. From these plasma glucose measurements, fasting plasma glucose, 2-hour postprandial glucose (2pp), 2-hour postprandial glucose excursion (2pp(ex)), maximum glucose excursion (Gex(max)), the area under the glucose concentration versus time curve from 0 to 4 hours (AUC4), and the area under the glucose excursion versus time curve from 0 to 4 hours (AUCex4) were calculated. RESULTS: Because of significant differences in the baseline fasting plasma glucose levels between Mix75/25 and 70/30 (Mix75/25: 8.9+/-2.2 mmol/L [160.2+/-39.6 mg/dL]; 70/30: 8.6+/-1.9 mmol/L [154+/-34 mg/dL), analyses of the excursion parameters provide a truer comparison of the glucodynamic response between insulin formulations. Mix75/25 resulted in significantly lower values for 2pp(ex) (3.35+/-2.28 vs 4.13+/-2.26 mmol/L), Gex(max) (4.51+/-1.88 vs 5.19+/-1.98 mmol/L), and AUCex4 (8.01+/-7.02 vs 10.6+/-6.47 mmol x h/L) compared with 70/30. CONCLUSIONS: In patients with type 2 diabetes mellitus, premeal injection of Mix75/25 resulted in better postprandial glycemic control than did premeal injection of 70/30 in the 4 hours after a standard meal. Mix75/25 is a valuable option for managing postprandial blood glucose in patients with type 2 diabetes mellitus who require insulin.

Adult↗