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Biomedical subjects

Y P Lin

Publications and source records attributed to Y P Lin.

At least 37 records · Page 2Linked to original sources

Increased arterial wave reflection may predispose syncopal attacks.

BACKGROUND: The incidence of syncope increases with age, while aging is also associated with increased arterial wave reflection. HYPOTHESIS: The study was undertaken to determine whether increased arterial wave reflection is a predisposing factor of syncope. METHODS: We recruited 38 patients (28 men and 10 women, mean age 57.2 +/- 20.3 years, range 17-87 years) with a history of syncope within 6 months of entry. The etiology of syncope was documented for each patient by a complete assessment of vasomotor function and cerebral flow. All patients received a comprehensive echocardiographic evaluation of cardiac structure and function. Carotid augmentation index (AI) was estimated noninvasively with the tonometry technique. The results were compared with those from 54 age- and gender-matched controls. RESULTS: The most frequent diagnoses of syncope were postural hypotension (13 patients) and cerebrovascular dysautoregulation (10 patients), and the cause could not be determined in 9 patients. Compared with the control group, the syncope group had a greater AI (20 +/- 21 vs. 10 +/- 15%, p = 0.013). Subgroup analysis of 20 patients aged > 50 years and with the aforementioned diagnoses showed even more striking results: AI, 29 +/- 10 vs. 11 +/- 15%, p < 0.001. The enhanced augmentation in the patients remained when age, systolic blood pressure, height, and heart rate were accounted for. Analysis of the carotid pulse wave suggested that both the timing and intensity of wave reflection were enhanced in patients with a history of syncope compared with controls. CONCLUSIONS: Our results support the hypothesis that enhanced arterial wave reflection is associated with the occurrence of syncope, especially in the elderly.

Adolescent↗

Follow-up in the micronucleus frequencies and its subsets in human population with chronic low-dose gamma-irradiation exposure.

Forty-eight individuals, who received protracted low-dose rate gamma-irradiation from radioactive environments for 2-10 years, have been evaluated repetitively for cytogenetic damage by the cytochalasin-B micronuclei assay (CBMN) after they relocated from radioactive buildings. These subjects were shown to have a significant decrease in the CBMN frequencies during 26.2+/-8.4 months of follow-up. By the mixed effect multiple linear regression analysis, the CBMN frequencies in these 48 subjects during repetitive measurements were significantly associated with the relocation duration since leaving the radioactive environments (relocation time or RT in months; estimate -0.47, standard error 0. 0016, p value 0.0074). The alteration rate in the proportions of binucleates carrying a single micronucleus and those with multiple micronuclei was further compared among 26 of these exposed individuals. The proportions of binucleates with multi-micronuclei were shown to decline significantly faster than those with a mono-micronucleus between these two repetitive assays (proportional Z-test, p value 0.003). Moreover, some of the exposed subjects were shown to have a persistent increase in the total micronuclei frequencies or carrying multi-micronuclei in the binuclei even 3-4 years post-cessation of exposure. This suggests potential genomic instability in stem cells of the exposed individuals and the phenomenon deserves further closer monitoring. Understanding the dynamics of micronucleus expression in lymphocytes in subjects with previous mutagenic exposure would be of significant importance for human population monitoring.

Adolescent↗

Persistent leucocyte abnormalities in children years after previous long-term low-dose radiation exposure.

Two hundred and eighty-nine children who had been educated in a kindergarten during 1983-92 and received continuous low-dose whole body gamma-irradiation from 60Co-contaminated steel window frames in their classrooms were investigated for residual effects on their haematological tissues. Another 751 children, sex and age-matched, received similar but much lower exposure in an elementary school with classrooms built with contaminated steel rebars. The peripheral leucocytes of these children were examined 5-7 years after they had stopped using these irradiated classrooms. Children who received higher exposure in the kindergarten were shown to have a significant decrease in total leucocytes and neutrophils and an increase in eosinophils. Moreover, they were shown to be at significantly higher risk of developing relative leucopenia and neutropenia, but not lymphocytopenia, than those who received a lower exposure at the elementary school. Children from the kindergarten who had much higher exposure were shown to have a significant lowering of total leucocytes and neutrophils, and an increase in eosinophils years after exposure. Residual adverse haematological effects on the exposed children are strongly suspected.

Adolescent↗

Change in centromeric and acentromeric micronucleus frequencies in human populations after chronic radiation exposure.

Acute radiation exposure of humans was observed to induce various forms of cytogenetic damage, including increased frequencies of micronuclei and chromosomal aberrations. However, the cytogenetic effects of chronic low dose radiation exposure in vivo needs further characterization. Sixteen subjects with chronic low dose rates of gamma-radiation exposure from 60Co-contaminated steel in radioactive buildings were compared with seven non-exposed reference subjects for micronucleus frequencies after they relocated. By in situ hybridization using a digoxigenin-labeled anti-alpha all human centromere probe, the exposed subjects were shown to have a significant increase in cytochalasin B-modulated micronucleus (CBMN) frequencies, as well as a significant increase in centromere-positive (C+) CBMN, centromere-negative (C-) CBMN, total C+signals, single C+ MN signals and multiple C+ signals/1000 binucleated cells (BN). However, decreases in the ratios C+MN/C- MN and C+MN/total CBMN (%) were also noted in the exposed subjects. By mixed effects analysis, considering individuals from the same families, the C- MN and single C+ MN/1000 BN were both positively and moderately associated with previous cumulative exposure. When the time period of relocation post-exposure (relocation time or RT) was considered, total C+MN and multiple C+MN/1000 BN were negatively and significantly associated with RT. Moreover, the C+MN, C- MN, C+MN/C- MN ratio and single C+MN/1000 BN were all negatively and moderately associated with RT, but not with exposure dose. This suggested that acentromeric and single or multiple centromeric CBMN cytogenetic damage seems to disappear differentially in human subjects post chronic low dose radiation exposure.

Adolescent↗

Studies of the binding properties of influenza hemagglutinin receptor-site mutants.

Site-specific mutations have been made in the influenza hemagglutinin (HA) receptor binding site to assess the contribution of individual amino acid residues to receptor recognition. Screening of mutant HAs, expressed using recombinant vaccinia virus-infected cells, for their abilities to bind human erythrocytes indicated that substitutions involving conserved residues Y98F, H183F, and L194A severely restricted binding and that the substitution W153A prevented cell surface expression of HA. Mutation of residues E190 and S228 that are in positions to form hydrogen bonds with the 9-OH of sialic acid appeared to increase erythrocyte binding slightly, as did the substitution G225R. Substitutions of other residues that are directly or indirectly involved in receptor binding, S136T, S136A, Y195F, G225D, and L226P, had intermediate effects on binding between these two extremes. Estimates of changes in receptor binding specificity based on inhibition of binding to erythrocytes by nonimmune horse sera indicated that mutants G225R and L226P, unlike wild-type HA, were not inhibited; Y195F and G225D mutants were, like wild type, inhibited; and erythrocyte binding by mutants S136A, S136T, E190A, and S228G was only partially inhibited. Viruses containing mutant HAs Y98F, S136T, G225D, and S228G that cover the range of erythrocyte binding properties observed were also constructed by transfection. All four transfectant viruses replicated in MDCK cells and embryonated hens' eggs as efficiently as wild-type X-31 virus, although the Y98F mutant virus was unable to agglutinate erythrocytes. Mutant MDCK cells that have reduced levels of cell surface sialic acids were susceptible to infection by S136T, G225D, and S228G transfectant viruses and by wild type but not by the Y98F transfectant virus.

Animals↗

Chinese herbal medicine, sibship, and blood lead in children.

OBJECTIVES: Risk factors for increased blood lead concentration (BPb) has been investigated. However, the effect of sibship and Chinese herbal medicine on BPb has not been systematically studied. In this study BPb data from voluntary testing was used to determine if Chinese herbal medicine and sibship were associated with BPb. METHODS: 319 children aged 1-7 were tested for BPb. Meanwhile, parents were interviewed to obtain information including consumption of Chinese herbal medicine, living environment, lifestyle, and sibship of the children tested. RESULTS: The mean (SD) BPb of 319 preschool children was 4.4 (2.4) micrograms/dl. The consumption of Ba-baw-san (a Chinese herbal medicine) was significantly associated with increased BPb in children (p = 0.038). Further multivariate regression analysis of BPb in 50 pairs of siblings showed the factors of being brothers explained 75% of variation for BPb, and being sisters and brother-sister explained 51% and 41% of variation respectively. CONCLUSION: Chinese herbal medicine and children's play patterns within the family expressed in different types of sibship are the main determinants of low concentrations of BPb in preschool children of Taiwan.

Age Factors↗

Spiral computed tomographic angiography--a new technique for evaluation of vascular access in hemodialysis patients.

Spiral computed tomographic angiography (CTA), a new noninvasive imaging technique, was used to study 10 arteriovenous fistulas (AVF) in 9 hemodialysis patients. Digital subtraction angiography (DSA) was also performed as a gold standard for comparison. AVF stenosis was graded by a four-point scale: grade 0, well patency of supplying artery, anastomosis and drainage vein; grade 1, < 50% stenosis; grade 2, 50-70% stenosis; grade 3, 70-99% stenosis, and grade 4, total occlusion. We found CTA correlated closely to DSA in detecting both stenosis and dilatation of AVF and it spared all the shortcomings of DSA. CTA has the potential to be alternative for imaging of dialysis fistulas. Further studies will be performed to specify the role of CTA images in the assessment of the hemodialysis vascular access.

Adult↗

Adaptation of egg-grown and transfectant influenza viruses for growth in mammalian cells: selection of hemagglutinin mutants with elevated pH of membrane fusion.

A series of eight transfectant influenza viruses was generated by reverse genetics for studies of the palmitylated cysteine residues in the cytoplasmic tail of the hemagglutinin glycoprotein (HA). Following amplification of these viruses in MDCK cells we found that all had developed an elevated pH of membrane fusion--an unexpected result since previous mutant HA expression studies had shown that substitutions of the cysteine residues had no effect on fusion properties. Sequence analyses revealed that each of the viruses had at least one additional mutation in the ectodomain of HA which was responsible for the increase in fusion pH. Similarly, when we passaged egg-grown wild-type X-31 virus in three different lines of MDCK cells or in MDBK cells, high pH fusion mutants were selected within a few passages in every case. The locations of the substitutions in the HA structure are in or near the "fusion peptide" or at subunit interfaces throughout the length of the trimer--reminiscent of the changes selected in earlier studies on amantadine resistance. The observation that passage of certain viruses in mammalian cells can result in the selection of mutants with elevated fusion pH has potential implications both for reverse genetic experiments and, perhaps more importantly, for the choice of substrates for propagation of vaccine viruses.

Adaptation, Physiological↗

Peritoneal dialysis solution induces apoptosis of mesothelial cells.

For better simulation of the long-dwell exchanges in conventional CAPD, we have developed a modified mesothelial cell culture system consisting of a Transwell culture apparatus. The equilibration patterns of pH, dextrose and osmolality in the present culture system were observed to be very similar to those in human CAPD. The effects of six different peritoneal dialysis solutions on the apoptosis of mesothelial cells were evaluated using this modified culture system. The results imply that peritoneal dialysis solution per se may incite apoptosis of mesothelial cells, and also that low calcium peritoneal dialysis solution is a milder apoptosis stimulant as compared to the conventional peritoneal dialysis solution. Moreover, varying concentrations of dextrose in the peritoneal dialysis solution were not observed to significantly affect the apoptosis rate. The roles of ambient high concentrations of calcium and dextrose, low pH, as well as high osmolality in the apoptosis are also discussed.

Apoptosis↗

Fiber-supplemented enteral formula slows intestinal transit by intensifying inhibitory feedback from the distal gut.

Because an increase in flow rate accelerates intestinal transit, a reduction in the flow rate of formula delivery is recommended frequently for treatment of diarrhea that develops during enteral feeding. Because intestinal transit is slowed by nutrient-triggered inhibitory feedback, the rate of intestinal transit during enteral feeding may depend on a balance between the accelerating effect of flow and the inhibiting effect of the nutrient load. The addition of fiber to a formula may alter this balance. By delaying absorption of nutrients, fiber may extend the length of small intestine exposed to nutrients and thereby trigger more intense inhibitory feedback. To determine whether the addition of fiber favors nutrient-triggered inhibition over flow-driven acceleration, we studied intestinal transit after perfusion of a low-residue enteral formula compared with a fiber-supplemented formula at two perfusion rates (50 or 100 mL/h for 2 h) into the duodenum of dogs each with both a duodenal and midgut fistula. With the low-residue formula, intestinal transit accelerated when the flow rate increased from 50 to 100 mL/h (P < 0.05). With the fiber-supplemented formula, however, intestinal transit was inhibited regardless of the flow rate. To determine whether the fiber-supplemented formula inhibited intestinal transit by displacing nutrients distally, we compared intestinal transit when the two formulas, delivered at 100 mL/h, were diverted completely at the midgut fistula. Intestinal transit of the fiber-supplemented formula increased by 400%, eliminating the difference in intestinal transit speed between the two formulas. We concluded that the fiber-supplemented formula slowed intestinal transit by intensifying inhibitory feedback from the distal gut.

Analysis of Variance↗

[A new dynamic model of release for not-corroded drug system--revision and use of Fick's first law].

Based on the facts that the diffusion coefficient in original Fick's first law is not a strict constant but changes with concentration and that the original Fick's first law is only suitable for the stable diffusion with constant concentration gradient but many experiments have shown that the concentration gradient is a function of time. The authors suggest that the diffusion coefficient and the concentration gradient should be revised, respectively, as a concentration function and a time function. That is, [formula: see text] So, the Fick's first law is revised as [formula: see text] In the formula, dW/dt represents the rate of diffusion. D0 is the intrinsic diffusion coefficient that is a constant only concerning the temperature and the character of the substance diffused. A is the area of diffusion surface, alpha is the constant concerning the change of concentration gradient, C0 and C is, respectively, the concentration on the diffusion surface at time t0 and any time t. Based on this, the dynamic model of release on the preparations not-corroded is derived: [formula: see text] Here, k0 is the release constant concerning D0, temperature, C0 and A. The model gave better results than other models in common use for simulating the release dynamic process and the physical meanings of the model parameters are explicit.

Cellulose↗

Studies using double mutants of the conformational transitions in influenza hemagglutinin required for its membrane fusion activity.

Amino acid substitutions widely distributed throughout the influenza hemagglutinin (HA) influence the pH of its membrane fusion activity. We have combined a number of these substitutions in double mutants and determined the effects on the pH of fusion and on the pH at which the refolding of HA required for fusion occurs. By analyzing combinations of mutations in three regions of the metastable neutral-pH HA that are rearranged at fusion pH we obtain evidence for both additive and nonadditive effects and for an apparent order of dominance in the effects of amino acid substitutions in particular regions on the pH of fusion. We conclude that there are at least three components in the structural transition required for membrane fusion activity and consider possible pathways for the transition in relation to the known differences between neutral and fusion pH HA structures.

Aspartic Acid↗

Macromolecular adducts of butadiene.

Butadiene (BD) is an important industrial chemical classified as a probable human carcinogen. Marked species differences in susceptibility to the carcinogenic effects of BD have been observed, possibly due to the differences in its metabolism. In this work, guanine and adenine adducts formed by the reactive metabolites of BD in vitro were isolated and structurally characterized by UV spectroscopy, liquid secondary ion mass spectrometry and tandem mass spectrometry, electrospray mass spectrometry and nuclear magnetic resonance spectroscopy. The adducts were prepared by reacting purine nucleobases or nucleosides with epoxybutene (EB) or diepoxybutane (DEB) followed by HPLC separation. The reaction of guanine (Gua) with EB resulted in two isomeric products, N7-(2-hydroxy-3-buten-1-yl)guanine (EB-Gua I) and N7-(1-hydroxy-3-buten-2-yl)guanine (EB-Gua II). The reaction of adenine at N3 led to the formation of N3-(2-hydroxy-3-buten-1-yl)adenine (EB-Ade I) and N3-(1-hydroxy-3-buten-2-yl) (EB-Ade II). The major guanine adduct with DEB was identified as N7-(2',3', 4'-trihydroxybutyl)guanine (DEB-Gua-I). Three products formed from the reaction of DEB with adenine at pH 7 were identified as N3, N7 and N9-(2',3',4'-trihydroxybutyl)adenines (DEB-Ade I, II and III, respectively). Our results indicate that nucleophilic nitrogens of guanine and adenine first attack one of the epoxy groups of DEB giving (2'-hydroxy-3',4'-epoxybutane-1-yl) intermediates which can be rapidly hydrolyzed to the corresponding (2',3',4'-trihydroxybutyl) adducts or form cross-links with DNA or proteins. N7 and N3 adducts of Ade and Gua are expected to undergo spontaneous depurination and repair by methylpurine glycosylase and therefore may be useful as biomarkers of exposure in urine. The preliminary data on quantification of EB-induced N-terminal valine hemoglobin adducts in red blood cells of exposed mice and rats using modified Edman degradation followed by GC-NI MS was investigated. The amount of EB-N-terminal valine adducts in mouse globin was about 3 times greater than that in rats which may be explained by higher rates of the formation and/or limited detoxification of EB in mice. Female rats and mice had greater amounts of hemoglobin adducts than males.

Adenine↗

Genetic reassortment in pandemic and interpandemic influenza viruses. A study of 122 viruses infecting humans.

The human influenza pandemics of 1957 and 1968 were caused by reassortant viruses that possessed internal gene segments from avian and human strains. Whether genetic reassortment of human and avian influenza viruses occurs during interpandemic periods and how often humans are infected with such reassortants is not known. To provide this information, we used dot-blot hybridization, partial nucleotide sequencing and subsequent phylogenetic analysis to examine the 6 internal genes of 122 viruses isolated in humans between 1933 and 1992 primarily from Asia, Europe, and the Americas. The internal genes of A/New Jersey/11/76 isolated from a human fatality at Fort Dix, New Jersey in 1976 were found to be of porcine origin. Although none of the geographically and temporally diverse collection of 122 viruses was an avian-human or other reassortant, cognizance was made of the fact that there were two isolates from children from amongst 546 influenza A isolates obtained from The Netherlands from 1989-1994 which were influenza A reassortants containing genes of avian origin, viruses which have infected European pigs since 1983-1985. Thus, genetic reassortment between avian and human influenza strains does occur in the emergence of pandemic and interpandemic influenza A viruses. However, in the interpandemic periods the reassortants have no survival advantage, and the circulating interpandemic influenza viruses in humans do not appear to accumulate avian influenza virus genes.

Base Sequence↗

N-cubylmethyl substituted morphinoids as novel narcotic antagonists.

N-Cubylmethylnormorphine (1) and N-cubylmethylnoroxymorphone (2) have been synthesized and found to be more potent ligands at the mu and kappa opioid receptors than morphine and oxymorphone respectively. In the guinea-pig ileum preparation, compounds 1 and 2 were characterized as opioid mu antagonists (Ke = 68 and 16 nM, respectively). Compound 2 also showed effective kappa-antagonism (Ke = 22 nM). The narcotic antagonism activity of 1 has been confirmed by in vivo assays.

Analgesics, Opioid↗

Detection of pathogenic Yersinia enterocolitica using the multiplex polymerase chain reaction.

A multiplex polymerase chain reaction (PCR) was developed to detect the presence of the ail, yst, and virF genes of Yersinia enterocolitica simultaneously, quickly and accurately. The amplified fragment sizes were 356 base-pairs (bp) for the ail gene, 134 bp for the yst gene, and 231 bp for the virF gene. The specificity of the amplified products was confirmed by hybridization with digoxigenin-labelled oligonucleotide probes. Amplification was successful whether the template was derived from a single colony of bacteria, aliquots of boiled bacterial suspensions, from DNA extracted from pure or mixed cultures or from stool specimens. Amplification of the virF gene was also achieved from strains of Y. pseudotuberculosis carrying the 70 kb plasmid but not with preparations from other related Yersinia species or from other members of the family Enterobacteriaceae. The detection limit we established was 5-10 colony forming units per millilitre (cfu/ml) and 1.0 pg of DNA.

Animals↗

A simplified method of timing frozen embryo transfers.

OBJECTIVE: Our purpose was to compare a simple artificial hormone replacement regimen with two other protocols incorporating pituitary down-regulation with gonadotropin-releasing hormone agonist for frozen embryo transfers. STUDY DESIGN: We performed a retrospective analysis of pregnancy outcomes after 366 frozen embryo transfers timed by one of three hormone replacement regimens. The three regimens used were regimen A, leuprolide acetate and transdermal estradiol patches; regimen B, leuprolide acetate and oral micronized estradiol; regimen C, only oral micronized estradiol. RESULTS: The outcomes of 366 consecutive frozen embryo transfers according to one of the three regimens were compared and analyzed. The clinical pregnancy rates were 13.7%, 11.4% and 13.5% in regimens A, B and C, respectively. No statistical differences were found among the three regimens. The mean age of the patients in the three groups was comparable. The mean number of frozen embryos transferred with regimen B was slightly higher, but it did not have a positive impact on the pregnancy rate in this group. CONCLUSION: Controlled sequential hormone replacement results in an endometrium suitable for frozen embryo transfers. Pituitary down-regulation is not necessary. Therefore this regimen is not only more simple to use but also more economical.

Cryopreservation↗