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Biomedical subjects

T Yu

Publications and source records attributed to T Yu.

At least 55 records · Page 3Linked to original sources

Catalytic asymmetric allylation reactions using BITIP catalysis and 2-substituted allylstannanes as surrogates for beta-keto ester dianions.

[formula: see text] Catalytic asymmetric allylation (CAA) reactions using the indicated allylstannane and the BITIP catalysts previously described by us give high yields and enantioselectivities in additions to aldehydes. The products are convertible to beta-keto esters by oxidative cleavage of the olefin. These reactions thus provide a useful catalytic enantioselective method for chain extension with introduction of a versatile four-carbon unit.

Allyl Compounds↗

Control of 3' splice site choice in vivo by ASF/SF2 and hnRNP A1.

The constitutive splicing factor ASF/SF2 has been shown to affect the choice between alternative splice sites by favoring the proximal as opposed to the distal choice. HnRNP A1 antagonizes ASF/SF2 by promoting the distal choice for competing 5' splice sites. We have tested the in vivo effects of these proteins on alternative 3' splice site choices. Cotransfection of a dihydrofolate reductase-calcitonin chimeric construct togetherwith a plasmid specifying the SR protein ASF/SF2 into cells of several mammalian lines increased use of a proximal 3' splice site, resulting in the inclusion of a terminal calcitonin exon. This stimulation of 3' proximal splicing was antagonized by cotransfection with an hnRNP A1 plasmid. This effect of hnRNP A1 in promoting distal splicing was also seen in an hnRNP A1-deficient MEL cell line. A similar effect of hnRNP A1 was demonstrated with mutant hamster adenine phosphoribosyltransferase (aprt) transcripts that are normally constitutively spliced, suggesting that hnRNP A1 may be a general inhibitor of proximal splicing. Intron size also influenced splice site choice in mutant aprt transcripts, with larger introns favoring proximal splicing. These results support the idea that the ratios of particular but general splicing factors and hnRNPs play a role in alternative splicing.

3' Untranslated Regions↗

Nonlinear behavior of vocal fold vibration: the role of coupling between the vocal folds.

Coupling between the vocal folds is one of the nonlinear mechanisms allowing regulation and synchronization of mucosal vibration. The purpose of this study was to establish that modulations such as diplophonia and abnormalities observed in vocal signals that may be observed in some cases of laryngeal pathology can be considered as nonlinear behavior due to the persistence of some physical interaction (coupling). An experimental model using excised porcine larynx was designed to create tension asymmetry between the vocal folds and to obtain vocal signals with modulations. Signals were analyzed by spectral analysis and the phase portrait method. Results were compared with computer-generated synthetic signals corresponding to nonlinear combinations of sinusoid signals. Under these conditions, evidence of nonlinear behavior was detected in 85% of experimental signals. These findings were interpreted as a demonstration of vocal fold interaction. Based on these findings, the authors conclude that (1) coupling must be taken into account in physical models of laryngeal physiology, and that (2) methods of nonlinear dynamics may be used for objective voice analysis.

Animals↗

Adaptation of very virulent infectious bursal disease virus to chicken embryonic fibroblasts by site-directed mutagenesis of residues 279 and 284 of viral coat protein VP2.

The full-length RNA genomes of a chicken embryonic fibroblast (CEF)-nonpermissive, very virulent infectious bursal disease virus (IBDV) (strain HK46) were amplified into cDNAs by reverse transcription-PCR. The full-length cDNAs were sequenced and subcloned into a eukaryotic expression vector, from which point mutations were introduced into the VP2 region by site-directed mutagenesis. The wild-type and mutated plasmids were transfected directly into CEFs to examine their ability to generate CEF-permissive recombinant viruses. Substitution of amino acid residues 279 (Asp-->Asn) and 284 (Ala-->Thr) of the VP2 protein yielded a recombinant virus which was able to be passaged in CEFs, whereas the wild-type cDNAs and an amino acid substitution at residue 330 (Ser-->Arg) of the VP2 protein alone did not yield viable virus. The results indicated that mutation of other viral proteins, including VP1, VP3, VP4, and VP5, was not required for CEF adaptation of the virus. The same approach may be used to produce CEF-adapted strains from newly evolved IBDVs or to manipulate the antigenicity of the virus.

Amino Acid Sequence↗

A high dose of ionizing radiation induces tissue-specific activation of nuclear factor-kappaB in vivo.

Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) is one of the important responses of cells to an external stress such as ionizing radiation. We studied radiation-induced NF-kappaB activation in vivo in male BALB/c mice. After the mice were exposed to 8.5 Gy total-body gamma irradiation, the spleen, mesenteric lymph nodes, thymus, liver, lung, colon, brain and bone marrow were harvested 1, 2.5, 5, 10 and 20 h postirradiation. NF-kappaB DNA-binding activity was analyzed in the nuclear protein extracts by a gel shift assay. When compared to the levels in untreated control mice, radiation induced activation of NF-kappaB in spleen, mesenteric lymph nodes and bone marrow but not in the other tissues examined. In contrast, an i.p. injection of a lethal dose (3 mg/kg) of lipopolysaccharide also increased activity of NF-kappaB in the liver and lung. The gel supershift assay with Nfkb1, Rela and/or Rel antibodies revealed that the specific molecular forms of NF-kappaB activated by radiation in the spleen were Nfkb1 homodimers and Nfkb1/Rela heterodimers. In mesenteric lymph nodes, the heterodimerized Rel/Rela NF-kappaB was also activated. In bone marrow, an NF-kappaB-like binding factor was induced that may be Nfkb1/Rela- and Rel/Rela-like heterodimers, but it exhibited a higher mobility than Nfkb1 homodimers. These results indicate that in vivo, ionizing radiation induces NF-kappaB activation that varies in both tissue distribution and moleoular composition.

Animals↗

[The diagnostic significance of antineutrophil cytoplasmic antibodies in ulcerative colitis].

OBJECTIVE: To inquire into the diagnostic significance of antineutrophil cytoplasmic antibodies (ANCA) in ulcerative colitis (UC). METHODS: Serum ANCA from 58 UC patients, 43 non-UC patients and 58 healthy donors were detected with indirect immunofluorescence (IIF), enzyme linked immunosorbent assay (ELISA)and Western blot. RESULTS: The sensitivity and specificity of the presence of ANCA in the diagnosis of UC were 37.93% and 100% respectively. In the group of UC, patients with mild, moderate and severe clinical manifestations had positive ANCA rates of 17.65%, 41.67% and 52.94% respectively. The occurrence rates of mucosal vasculitis and grade III-V mucosal inflammation were 78.95% and 78.95% respectively in ANCA-positive group, but 37.04% and 44.44% in ANCA-negative group. The levels of the binding of the five kinds of ANCA antigens i.e. myeloperoxidase (MPO), bactericidal/permeability increasing protein (BPI), lactoferrin (LF), cathepsin G (CG) and proteinase-3 (PR-3) with the serum of UC patients were 13.99%, 13.79%, 10.34% 10.34% and 8.62% respectively. Specific protein strips were observed in 48.28% of the UC patients with Western blot technique, 47,000 polypeptide being the most common and making up 22.41% of them. CONCLUSION: The detection of ANCA was an auxiliary method for the diagnosis of UC. At present, UC-associated target antigens were not yet clarified, 47,000 polypeptide may be one of them. ANCA may participate in the pathogenesis of UC.

Adolescent↗

[Time trend of mortality rates of cerebrovascular diseases in Hong Kong].

OBJECTIVE: To describe the time trend of mortality rates of cerebrovascular diseases (CVD) in Hong Kong for the period of 1976 to 1995, and to compare them with those in the more developed countries around the world. METHODS: Mortality rates of CVD were standardized directly using world standard population in 1961. Annual percent changes of mortality rates of CVD were estimated with a non-linear regression. Birth-cohort analysis was carried out at an interval of five-year of age to compare their age-specific mortality rates of CVD in different birth cohorts. Time trend of cause-specific mortality rates of CVD both in males and females was fitted with a simple linear regression model. RESULTS: Considerable downward trend of CVD mortality was observed during the past twenty years. Mortality rates among men and women decreased by 50.96% and 37.85% in 1995, as compared to those in 1976, respectively. Although in general, a greater trend in CVD mortality was observed during the last 10 years, as compared with that in the previous 10 years, an annual increase in CVD mortality of 1.34% was found among males aged 35 to 44 years during the latter 10 years. CVD mortality for both males and females decreased steadily by 1% per year. CVD mortality for females will catch up with that for males by the year of 2013, if such a trend continues. Birth-cohort analysis showed that those born more recently at the same age-group had lower mortality of CVD (except for those born after 1955). Data from hospital admission showed that improvement in the treatment for CVD could have contributed partly to the decrease in its mortality. CONCLUSION: Time trend of mortality of CVD in Hong Kong was similar to that in many other economically developed areas around the world.

Adult↗

Solution structure of a fragment of the dimerization domain of DP-1 determined by 1H-nuclear magnetic resonance and distance geometry.

The structure of a synthesized peptide with the sequence of NHILPNESAYDQKNIRRRVYDALNVLMAMNIISK that corresponds to residues 151-184 of transcription factor DP-1 (Girling et al., Nature 362 (1993) 83-87) was determined by 1H-nuclear magnetic resonance in water and 40% d3-trifluoroethanol/water, respectively. Nuclear Overhauser effect cross peaks, alphaH chemical shifts and J-coupling constants of alphaH-NH show that the peptide consists a helix from Ser-8 to Ser-33 in solution. Fifty structures were constructed with 288 upper distance limits and 21 angle constraints by DIANA (Guntert et al., J. Mol. Biol. 217 (1991) 517-530). Although the N-terminal of the peptide exhibits a random conformation, the 20 best structures show a root mean square deviation of 0.89+/-0.36 A for backbone atoms and 1.80+/-0.34 A for heavy atoms from residue Ser-8 to Ser-33. This result supports the proposal that DP-1 and E2F-1 may dimerize with a coiled-coil type interaction.

Amino Acid Sequence↗

Expression of GDNF family receptor components during development: implications in the mechanisms of interaction.

Glial cell line-derived neurotrophic factor (GDNF) and a related factor, neurturin, promote survival of diverse groups of neurons. Both GDNF and neurturin signal via a two-component receptor complex that consists of a ligand-binding GDNF family receptor (GFRalpha-1 or GFRalpha-2) and the receptor protein tyrosine kinase Ret. Recently, a third receptor related to GFRalpha-1 and GFRalpha-2 has also been isolated and designated GFRalpha-3. Although much is known about the interaction among GDNF family factors, Ret, and the alpha-receptors in vitro, it remains unclear about their interactions in vivo. We show here by in situ hybridization that Ret and the alpha-receptors may be colocalized in the same tissues or expressed separately in projecting and target tissues, respectively, indicating that two distinct modes of interaction between Ret and the alpha-receptors exist in vivo. First, Ret may interact with the alpha-receptors expressed in the same cells (termed interaction "in cis") in many tissues and cell populations that respond to GDNF and/or neurturin, such as the substantia nigra, dorsal root ganglia, spinal cord motoneurons, kidney, and intestine. Second, Ret may interact with the alpha-receptors localized in the target neurons (termed interaction "in trans"). In addition, we present evidence in vitro that GFRalpha-1 mediates Ret activation by GDNF in trans. These observations suggest that there are multiple mechanisms regulating the interaction between Ret and the alpha-receptors that mediates the effects of GDNF family trophic factors on the survival and differentiation of cells and on neuron-target interactions in the nervous system.

Aging↗

Retinopathy in older persons without diabetes and its relationship to hypertension.

OBJECTIVE: To assess the prevalence and relationship of retinopathy lesions in older subjects without diabetes to systemic hypertension. METHODS: Three thousand six hundred fifty-four people aged 49 years or older attending the Blue Mountains Eye Study underwent a detailed eye examination, including medical history, blood pressure measurement, and fasting blood collection. Retinopathy lesions (hemorrhages and microaneurysms) were assessed from masked grading of stereoretinal photographs. Subjects with a history of diabetes or an elevated blood glucose level were excluded. Hypertension was defined as the current use of antihypertensive medications or an elevated blood pressure measurement on examination. RESULTS: Retinopathy was present in 325 subjects without diabetes, a prevalence of 9.8% (95% confidence interval [CI], 8.9%-10.9%), which increased with age. An increased age-adjusted relative risk (RR) for retinopathy was found for women (RR, 1.67; 95% CI, 1.26-2.21) and men (RR, 1.47; 95% CI, 1.07-2.00) with hypertension. In people using antihypertensive medications, retinopathy prevalence was higher for uncontrolled compared with controlled blood pressure but was not related to hypertension duration. Significant (P=.02 to P=.001) trends were found between increasing blood pressure quartiles and age-adjusted retinopathy prevalence, a relationship that was maintained after adjusting for fasting plasma glucose level at 3 diagnostic cut points for diabetes. CONCLUSIONS: This study supports the Beaver Dam Eye Study findings that retinal hemorrhages and microaneurysms are relatively frequent lesions in older people without diabetes and are significantly related to the presence and severity of hypertension.

Aged↗

Antigenic characterization of HIV-1 gp41 binding proteins.

The envelope protein HIV-1 gp41 has been shown to exert various effects on human T-cells, B-cells and monocytes like inhibition of cell proliferation, modulation of MHC expression and cytokine production. In contrast to gpl20, where several receptor molecules have been identified, the receptor for gp41 is still unknown. Using a sepharose column, coupled with recombinant soluble gp41, (rsgp41; Env amino acids 539-684), five gp41-binding proteins of 37, 45, 50, 62 and 100 kDa had been isolated from lysates of the B-cell line Raji. Two mouse antiserums were generated against the proteins P45 and P62 and were tested against the binding specificity of both antiserums. In Western blot analysis the antiserums recognized two protein bands of 45 and 62 kDa in complete Raji cell lysates, as well as the purified proteins P45 and P62, respectively, but did not show any cross-reaction, indicating that the two proteins do not share any immunological epitopes. Besides, the polyclonal antiserums did not recognize the other gp41-binding proteins P37, P50 and P100. Using the P62 antiserum proteins of the same size as in Raji cell lysates were stained in the lysates of the monocytic cell line U937 and the T-cell line H9, demonstrating distribution of P62 in different blood cells. P45 seems not to be identical to HLA-C which had been shown to bind to gp41. These results indicate, that P45 and P62 are two separate gp41-binding proteins without homology to each other or to the other gp41-binding proteins.

Animals↗

Mammography spectrum measurement using an x-ray diffraction device.

The use of a diffraction spectrometer developed by Deslattes for the determination of mammographic kV is extended to the measurement of accurate, relative x-ray spectra. Raw x-ray spectra (photon fluence versus energy) are determined by passing an x-ray beam through a bent quartz diffraction crystal, and the diffracted x-rays are detected by an x-ray intensifying screen coupled to a charge coupled device. Two nonlinear correction procedures, one operating on the energy axis and the other operating on the fluence axis, are described and performed on measured x-ray spectra. The corrected x-ray spectra are compared against tabulated x-ray spectra measured under nearly identical conditions. Results indicate that the current device is capable of producing accurate relative x-ray spectral measurements in the energy region from 12 keV to 40 keV, which represents most of the screen-film mammography energy range. Twelve keV is the low-energy cut-off, due to the design geometry of the device. The spectrometer was also used to determine the energy-dependent x-ray mass attenuation coefficients for aluminium, with excellent results in the 12-30 keV range. Additional utility of the device for accurately determining the attenuation characteristics of various normal and abnormal breast tissues and phantom substitutes is anticipated.

Biophysical Phenomena↗

Vitamin D receptor alleles predict growth and bone density in girls.

OBJECTIVES: Polymorphism of the vitamin D receptor (VDR), collagen alpha I type I (Col I alpha I), and oestrogen receptor (ER) genes have been shown to account for some of the heritability of bone mineral density (BMD) in adults. This study examined this relation in prepubertal children. METHODS AND SUBJECTS: The relation between genotypes of VDR gene (Taq I, Bsm I, Fok I), Col I alpha I gene (Msc I), and ER gene (Pvu II) with areal BMD, volumetric BMD, and growth were examined in 114 (68 girls) healthy 7 year old, white children. RESULTS: The genotype of the VDR gene (Taq I) correlated with lumbar spine (L1-4) volumetric BMD in girls only, but at no other bone sites. In girls, VDR genotype affected areal BMD at all sites. After adjusting for height and weight, however, this effect was explained completely by the independent effect of the VDR genotype on growth. Girls with genotype TT, were 3.9 kg heavier and 4.1 cm taller than those with tt, but this relation was not present at birth. No relation was found between genotypes of the VDR gene (Fok I), Col I alpha I gene (Msc I), or ER gene (Pvu II) and BMD or growth variables. CONCLUSIONS: In prepubertal girls, VDR alleles contribute to lumbar spine volumetric BMD variance, but the areal BMD effect reflects the relation between areal BMD and growth. VDR alleles might affect postnatal growth regulation.

Alleles↗

[The fluorescence properties of DaYaWan soil humic acid].

The fluorescence properties of humic acid derived from DaYaWan soil were analyzed using the conventional fluorescence and synchronous scan fluorescence spectroscopy. The results show that synchronous technique applied to the study of humic acid can reduce the fluorescence spectrum of a compound to a single sharp peak, and decrease the signal overlapping. In addition, the effects of various deltalambda, concentration and pH values on synchronous fluorescence spectroscopy were investigated in detail.

China↗