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Biomedical subjects

A Yeh

Publications and source records attributed to A Yeh.

16 recordsLinked to original sources
PubMed2002

Quantum phase transition in a common metal.

The classical theory of solids, based on the quantum mechanics of single electrons moving in periodic potentials, provides an excellent description of substances ranging from semiconducting silicon to superconducting aluminium. Over the last fifteen years, it has become increasingly clear that there are substances for which the conventional approach fails. Among these are certain rare earth compounds and transition metal oxides, including high-temperature superconductors. A common feature of these materials is complexity, in the sense that they have relatively large unit cells containing heterogeneous mixtures of atoms. Although many explanations have been put forward for their anomalous properties, it is still possible that the classical theory might suffice. Here we show that a very common chromium alloy has some of the same peculiarities as the more exotic materials, including a quantum critical point, a strongly temperature-dependent Hall resistance and evidence for a 'pseudogap'. This implies that complexity is not a prerequisite for unconventional behaviour. Moreover, it should simplify the general task of explaining anomalous properties because chromium is a relatively simple system in which to work out in quantitative detail the consequences of the conventional theory of solids.

Journal Article↗
PubMed2001

Oxidative dehydrogenation on the alpha-carbon of 4-pyridylacetonitrile complexes of pentaammineruthenium(II).

The oxidation of Ru(NH(3))(5)NCCH(2)py(2+) in 0.10 M HCl turns the solution from yellow to greenish blue with an absorption at lambda = 791 nm. The absorbance reaches its maximum value when the complex undergoes a two-electron oxidation. The IR and (1)H NMR spectra of the product indicate that the metal center remains as Ru(II) and that the ligand is oxidized. The (13)C NMR spectral results suggest that the oxidation product is [(NH(3))(5)RuNCC(pyH)C(pyH)CNRu(NH(3))(5)](ClO(4))(6). Cyclic voltammetry of the product solution also indicates that the oxidation proceeds in two one-electron steps corresponding to [Ru(III),Ru(II)] + e(-) <= => [Ru(II),Ru(II)] and [Ru(III),Ru(III)] + e(-) <= => [Ru(III),Ru(II)]. The structure of the product in deprotonated form [(NH(3))(5)RuNCC(py)C(py)CNRu(NH(3))(5)](ClO(4))(4)(H(2)O)(2) was determined crystallographically. [(NH(3))(5)RuNCC(py)C(py)CNRu(NH(3))(5)](ClO(4))(4)(H(2)O)(2) crystallizes in the orthorhombic Pbca space group with cell constants a = 13.7138 (16) A, b = 15.7553 (18) A, c = 17.831(2) A, and Z = 4. A mechanism for the oxidation has been proposed on the basis of the kinetic studies in the region of 0.01-0.20 M acid concentrations.

Journal Article↗
PubMed2000

Evasion of host defenses by measles virus: wild-type measles virus infection interferes with induction of Alpha/Beta interferon production.

Measles is a highly contagious disease currently responsible for over one million childhood deaths, particularly in the developing world. Since alpha/beta interferons (IFNs) are pivotal players both in nonspecific antiviral immunity and in specific cellular responses, their induction or suppression by measles virus (MV) could influence the outcome of a viral infection. In this study we compare the IFN induction and sensitivity of laboratory-passaged attenuated MV strains Edmonston and Moraten with those of recent wild-type viruses isolated and passaged solely on human peripheral blood mononuclear cells (PBMC) or on the B958 marmoset B-cell line. We report that two PBMC-grown wild-type measles isolates and two B958-grown strains of MV induce 10- to 80-fold-lower production of IFN by phytohemagglutinin-stimulated peripheral blood lymphocytes (PBL) compared to Edmonston and Moraten strains of measles. Preinfection of PBL with these non-IFN-inducing MV isolates prevents Edmonston-induced but not double-stranded-RNA-induced IFN production. This suggests that the wild-type viruses can actively inhibit Edmonston-induced IFN synthesis and that this is not occurring by double-stranded RNA. Furthermore, the wild-type MV is more sensitive than Edmonston MV to the effect of IFN. MV is thus able to suppress the synthesis of the earliest mediator of antiviral immunity, IFN-alpha/beta. This could have important implications in the virulence and spread of MV.

Animals↗
PubMed2000

Blocking the initiation of coagulation by RNA aptamers to factor VIIa.

The tissue factor/factor VIIa complex is thought to be the primary initiator of most physiologic blood coagulation events. Because of its proximal role in this process, we sought to generate new inhibitors of tissue factor/factor VIIa activity by targeting factor VIIa. We employed a combinatorial RNA library and in vitro selection methods to isolate a high affinity, nuclease-resistant RNA ligand that binds specifically to coagulation factor VII/VIIa. This RNA inhibits the tissue factor-dependent activation of factor X by factor VIIa. Kinetic analyses of the mechanism of action of this RNA suggest that it antagonizes factor VIIa activity by preventing formation of a functional factor VII/tissue factor complex. Furthermore, this RNA significantly prolongs the prothrombin time of human plasma in a dose dependent manner, and has an in vitro half-life of approximately 15 h in human plasma. Thus, this RNA ligand represents a novel class of anticoagulant agents directed against factor VIIa.

Base Sequence↗
PubMed1999

Comparison of the sensitivity and specificity of an automatic ligase chain reaction assay system with a one-step polymerase chain reaction assay in the diagnosis of Mycobacterium tuberculosis complex.

BACKGROUND: Polymerase chain reaction (PCR) and ligase chain reaction (LCR) are two nucleic acid amplification-based molecular methods. The former has been used widely in the identification of Mycobacterium tuberculosis (M. tuberculosis). In contrast, the LCR assay which was recently introduced is not well known in our medical communities in Taiwan. To determine which method is more reliable and suitable for the identification of M. tuberculosis in our clinics, we compared the sensitivity and specificity of these two methods. METHODS: An automatic LCR assay system and a manual one-step PCR assay were studied in a side by side comparison of their performance in detection of M. tuberculosis. The automatic LCR system uses the single copy antigen protein b (Pab) gene and the manual one-step PCR assay uses the multi-copy IS6110 insertion element as the target DNA; both target DNA sequences are found specifically in M. tuberculosis complex. RESULTS: Both assays detected two of the M. tuberculosis complex strains, M. tuberculosis and M. bovis, but not other mycobacterial strains. In addition, both methods, which were based on different amplification principles, showed compatible sensitivity; as low as 10 and 100 copies of M. tuberculosis genomes were detected by the LCR and PCR assays, respectively. When the template DNA was less than 1000 copies, however, the automatic LCR assay system showed a lower reproducibility than that of the one-step PCR assay. CONCLUSION: Our results suggest that in addition to the PCR assay, the LCR assay is a useful method for the molecular identification of M. tuberculosis complex strains.

DNA Ligases↗
PubMed1997

Femtosecond Dynamics of Excited-State Evolution in

Time-resolved absorption spectroscopy on the femtosecond time scale has been used to monitor the earliest events associated with excited-state relaxation in tris-(2,2'-bipyridine)ruthenium(II). The data reveal dynamics associated with the temporal evolution of the Franck-Condon state to the lowest energy excited state of this molecule. The process is essentially complete in approximately 300 femtoseconds after the initial excitation. This result is discussed with regard to reformulating long-held notions about excited-state relaxation, as well as its implication for the importance of non-equilibrium excited-state processes in understanding and designing molecular-based electron transfer, artificial photosynthetic, and photovoltaic assemblies in which compounds of this class are currently playing a key role.

Journal Article↗
PubMed1997

Regulation of the signal transduction program by drugs.

The purpose of this paper was to clarify critical aspects of the behavior of signal transduction activity in normal and cancer cells. 1. Signal transduction activity in the conversion of phosphatidylinositol through PI and PIP kinases and PLC to IP3 is regulated at multiple sites. In liver, hepatomas and human carcinomas PIP kinase is the rate limiting enzyme and PLC activity is present in great excess. 2. The steady-state signal transduction activity as measured by the three enzyme activities and IP3 concentration was markedly up-regulated in rat hepatomas of different growth rates. The steady-state specific activities of the three signal transduction enzymes were elevated in ovarian carcinomas as compared to normal ovary. Increased enzyme activities were also observed in human breast carcinoma cells as compared to normal human breast parenchymal cells. In breast, ovarian and rat hepatoma cells as they go through lag, log and plateau phases, IP3 concentration in the early lag phase increased 4.5- to 20-fold and PI and PIP kinase activities peaked in mid-log phase. These events returned to baseline levels in the plateau phase. PLC activity did not change. 3. The bone marrow PI and PIP kinase activities in 3-day starvation were decreased to 13% and IP3 concentration was reduced to 24%; at 1-day refeeding they returned to normal. PLC activity changed little. These alterations are in line with the rapid t1/2 degradation rates (12 min) of PI and PIP kinases observed in studies with cycloheximide. By contrast, PLC has a long half-life. 4. The molecular action of tiazofurin entails inhibition of IMP DH activity, decrease in GTP and IP3 concentrations, reduction of ras and myc oncogene expression, and signal transduction enzyme activities. These events are followed by induced differentiation and apoptosis. There are also decreases in enzyme activities which have rapid turnover, including TdR kinase, dTMP synthase, and GPRT. In vitro studies indicated that these events are abrogated by addition of guanine which restores GTP concentrations. Therefore, most or all these events were brought about by the reduced GTP concentration in the tiazofurin target cells. 5. Quercetin and genistein are able to inhibit PI and PIP kinase activities and reduce IP3 concentration in vivo and in tissue culture systems. These flavonoids are also inhibitors of cell proliferation and clonogenic ability in rat hepatoma 3924A and in human OVCAR-5 and MDA-MB-435 cells. Quercetin down-regulated the expression of c-myc and Ki-ras oncogenes and led to induced differentiation and apoptosis in K562 cells. Genistein reduced IP3 concentration in vivo and in the tissue culture system. Genistein is antiproliferative and has cytototoxicity in human carcinoma cells. All three drugs, tiazofurin, quercetin and genistein, act, in part at least, through depression of cellular IP3 concentration although the mechanisms may not be identical. 6. Quercetin and genistein, which attack different targets and different phases of the cell cycle, proved to be synergistic in OVCAR-5 cells. The impact of tiazofurin, genistein and quercetin is of interest because the drugs crucially inhibit the display of the neoplastic program of cells and lead to induced differentiation and apoptosis.

1-Phosphatidylinositol 4-Kinase↗
PubMed1997

Reversion by deletion of transforming oncogene following interferon-beta and retinoic acid treatment.

We have previously shown that prolonged interferon-beta (IFN-beta) treatment of RS485 cells (NIH3T3 cells transformed with multiple copies of an LTR-cHa-ras oncogene) resulted in the phenotypic reversion of 1%-5% of the culture, depending on the conditions used. This reversion persisted after IFN-beta was discontinued, although the revertants retained the LTR-cHa-ras and continued to express ras mRNA and p21. Clones were prepared of such persistent revertant cell lines (PRs). Expression of lysyl oxidase (LOX), which appears to act as a suppressor of ras transformation, was downregulated in RS485 and upregulated in the PRs. When retinoic acid (RA) was combined with IFN-beta treatment of the RS485 cultures, a different mechanism of reversion predominated. Following 60 days of treatment with 20 IU/ml of IFN-beta and 10 microM RA, all of the multiple (3-5) copies of the transforming LTR-c-Ha-ras originally present in RS485 cells were deleted from the genome in 72% of 54 revertant cell lines isolated. As in the case of revertants observed after treatment with IFN-beta alone, LOX mRNA expression was upregulated in all of the revertants that resulted from the treatment with IFN plus RA. The level of LOX mRNA expression acts, therefore, as an indicator of transformation in this system.

3T3 Cells↗
PubMed1993

Regulation of deoxycytidine kinase activity and inhibition by DFDC.

(1) Deoxycytidine kinase activity increased in a transformation- and progression-linked fashion in rat hepatomas of different proliferation rates. The activity also increased and was growth rate-linked in a series of tissue culture cell lines of human and animal tumors. (2) Deoxycytidine kinase activity was stringently linked with expression of the neoplastic proliferative program as it sharply increased in log phase in tissue culture cells of hepatoma 3924A and several human carcinoma strains. (3) Deoxycytidine kinase is subject to nutritional and hormonal regulation. On starvation the activity in liver decreased and on refeeding it returned to normal. Steroid hormone increased liver enzymic activity. Deoxycytidine kinase is substrate-inducible, since deoxycytidine injections in rat led to a 2- to 3-fold increase in hepatic enzyme activity. (4) Actinomycin or cycloheximide treatment blocked the increase in liver deoxycytidine kinase activity induced by steroid or deoxycytidine treatment. Therefore, it is assumed that the rise in deoxycytidine kinase activity requires new RNA and protein synthesis. (5) Cycloheximide treatment of rats carrying hepatomas yielded a t1/2 = 3.4 hr in the tumor for deoxycytidine kinase activity which was the shortest among the examined enzymes of purine and pyrimidine biosynthesis. (6) Actinomycin treatment of rats carrying hepatomas yielded a t1/2 of 5.8 hr for deoxycytidine kinase activity in the tumor which was one of the shortest in the examined enzymes of purine and pyrimidine biosynthesis. (7) Difluorodeoxycytidine (DFDC) is a competitive inhibitor (Ki = 7-28 microM) of deoxycytidine kinase from rat hepatoma and from human pancreatic carcinoma and ovarian carcinoma cells in culture.

Animals↗
PubMed1992

Induction of erythroid differentiation and fetal hemoglobin production in human leukemic cells treated with phenylacetate.

There is considerable interest in identifying nontoxic differentiation inducers for the treatment of various malignant and nonmalignant blood disorders, including inborn beta-chain hemoglobinopathies. Using the human leukemic K562 cell line as a model, we explored the efficacy of phenylacetate, an amino acid derivative with a low toxicity index when administered to humans. Treatment of K562 cultures with pharmacologically attainable concentrations of phenylacetate resulted in erythroid differentiation, evident by the reduced growth rate and increased hemoglobin production. The effect was time- and dose-dependent, further augmented by glutamine starvation (phenylacetate is known to deplete circulating glutamine in vivo), and reversible upon cessation of treatment. Molecular analysis showed that phenylacetate induced gamma globin gene expression with subsequent accumulation of the fetal form of hemoglobin (HbF). Interestingly, the addition of phenylacetate to antitumor agents of clinical interest, eg, hydroxyurea and 5-azacytidine, caused superinduction of HbF biosynthesis. The results suggest that phenylacetate, used alone or in combination with other drugs, might offer a safe and effective new approach to treatment of some hematopoietic neoplasms and severe hemoglobinopathies.

Azacitidine↗
PubMed1992

Post-transcriptional regulation by interferon-alpha of epsilon-globin production in human erythroleukemia K-562 cells.

Treatment of human K-562 erythroleukemia cells with interferon-alpha (IFN-alpha) resulted in a six-fold increase in the production of epsilon-globin, a component of embryonic hemoglobin, but in a two-fold or less augmentation of the production of other globin species. There was no comparable increase in the production of epsilon-globin mRNA following IFN treatment. We did, however, observe a shift in the cytoplasmic location of the epsilon-globin mRNA from the messenger ribonucleoprotein (mRNP) to the polysome fraction after IFN-alpha addition. No such shift was noted in the location of the mRNA for A gamma-globin, the major globin product of K-562 cells, which was always present in the polysome fraction. These results are significant with respect to the mechanisms of cellular regulation and differentiation induced by IFNs.

Antibodies, Monoclonal↗
PubMed1991

The "educated hand". Can anesthesiologists assess changes in neonatal pulmonary compliance manually?

To determine whether anesthesiologists can manually detect significant changes in pulmonary compliance in neonates using an "educated hand," the authors tested whether clinicians could detect clamping of an endotracheal tube connecting a neonatal lung model to one of three anesthesia breathing circuits. The test lungs corresponded to the lung of a full-term neonate (large lung) or a premature neonate (small lung), and the circuits were a disposable Mapleson D and a disposable pediatric circle system with and without a humidifier. Clinicians having four levels of expertise (inexperienced anesthesia residents, experienced anesthesia residents, faculty not specializing in pediatric anesthesia, and specialized pediatric anesthesia faculty) were permitted to choose fresh gas flows, ventilatory pattern, and rate. After an acclimation period, the endotracheal tube connecting the test lung to the circuit was occluded once for 30 s. Clinicians were credited with a successful detection if they reported the occlusion within 15 s and had fewer than one false positive per minute. With the large lung model, only 4 of 24 clinicians detected occlusion with the Mapleson D circuit; similar results were obtained with the other circuits. With the small lung model, the only successful detection occurred with the Mapleson D circuit. Success at detecting occlusion was similarly low for clinicians with different levels of expertise. The authors conclude that the commonly held belief that the "educated hand" permits clinicians to detect subtle changes in pulmonary compliance in neonates during anesthesia (necessitating manual rather than mechanical ventilation) is not true.

Anesthesiology↗
PubMed1991

Induction of alpha interferon by human immunodeficiency virus type 1 in human monocyte-macrophage cultures.

The induction of interferon (IFN) by human immunodeficiency virus type 1 (HIV-1) in primary, nonstimulated monocyte-macrophage cultures was studied. HIV-1 infection, as confirmed by p24 antigen levels in the cell supernatant, led to the production of alpha interferon (IFN-alpha) over 7 to 21 days following infection. In two of seven experiments, the IFN detected was acid labile. Coupled reverse transcription-polymerase chain reaction analysis confirmed the induction of IFN-alpha mRNA in cells of HIV-1-infected cultures.

Cell Adhesion↗
PubMed1985

Bilirubin production after supplemental oral vitamin E therapy in preterm infants.

The purpose of this investigation was to determine the influence of early vitamin E supplementation on the rate of heme catabolism (bilirubin production) in healthy preterm infants. Bilirubin production was estimated from the concentration of carbon monoxide in "end-tidal" gas. Serum vitamin E, hemoglobin, and bilirubin levels were determined by standard techniques. Thirty infants received supplementation with vitamin E or placebo in a double-blind, randomized fashion. Infants were studied on day 1 of life prior to therapy, and on days 3 and 7 postnatally. Results showed that in both placebo-supplemented and vitamin E-supplemented groups, vitamin E levels were significantly higher on days 3 and 7 compared with day 1. Bilirubin production was not significantly different on day 3 compared with day 1 in either group, but was significantly lower in both groups by day 7 compared with day 1. There were no significant differences in hemoglobin and serum bilirubin levels between the two groups at any point in time. In conclusion, although vitamin E supplementation significantly raises vitamin E levels, placebo-supplemented premature infants also achieve vitamin E sufficiency and a decrease in bilirubin production by day 7 of age.

Bilirubin↗