Biomedical subjects

Y Cha

Publications and source records attributed to Y Cha.

At least 19 recordsLinked to original sources

PubMed2000

[A primary study on distribution and binding forms of arsenic in polluted crop seeds].

The distribution, binding form and processing removal of arsenic in rice and wheat seeds were studied. The result shows that the distribution of arsenic in seed parts was uneven, as concentration in rice seed was embryo > seed capsule > chaff > endosperm, and that in wheat seed was embryo > seed capsule > endosperm. Arsenic was mainly accumulated in endosperm, and mainly in the form of protein-binding. With the removal of chaff, coarse rice bran and fine rice bran in the processing, the content of arsenic decreased by 16.51%, 12.41% and 10.26%, respectively. Similarly, with the removal of coarse wheat bran and fine wheat bran, it decreased by 22.0% and 45.6%, respectively.

Arsenic↗

PubMed1999

[Cancer mortality in high background radiation area of Yangjiang, China, 1979-1995].

OBJECTIVE: To estimate cancer risk associated with the low level radiation exposure of average annual effective dose of 6.4 mSv in HBRA the high background radiation area (HBRA) of Yangjiang, China. METHODS: The cancer mortality data of 1979-1986 were collected from a dynamic cohort by prospective survey. The data of 1987-1995 were obtained from a fixed cohort by retrospective and/or prospective survey. The mortality investigation on the spot consisted of two steps, i.e. the follow-up of the members in the cohort and the ascertainment of the death causes. The estimate of cumulative individual dose of the cohort members included that of the exposure from natural external and internal sources. Both direct (TLD measurement) and indirect (environmental measurement and occupancy pattern) approaches were used for individual external dose estimate. On the basis of the hamlet-specific average annual external dose, the cohort members were classified into four groups for internal comparison: high, medial and low dose groups from HBRA and control group from control area (CA). Relative risk (RR) and excess relative risk coefficient (ERR per sievert) and its 95% confidence interval (CI) was estimated using AMFIT program in Epicure. RESULTS: During the period 1979-1995, there were 10,415 total deaths and 1003 cancer deaths among 1,698,350 person-years at risk in the cohort of 125,079 subjects. The adjusted RR (95% CI) with sex and age group for all cancers of whole HBRA was 0.99 (0.87-1.14). As for the site-specific cancer of whole HBRA, the RRs of cancers of stomach, colon, liver, lungs, bone, female breast, and thyroid were less than one, while the RRs of cancers of nasopharynx, esophagus, rectum, pancreas, skin, cervix uterus, brain and central nervous system, leukemia and lymphoma were larger than one. However, all of them except for esophagus cancer were not different statistically from one (P > 0.05). The homogeneity tests of RRs for all cancers and for site-specific cancer among the three dose groups in HBRA revealed that the RRs in these dose groups were not different statistically (P > 0.05) for all. The ERR (95% CI)/Sv of all cancers for both sexes and all ages was -0.10 (-0.67, 0.69). CONCLUSION: An increased cancer risk associated with the high levels of natural radiation in HBRA was not found. On the contrary, the mortality of all cancers in HBRA was generally lower than that in CA, but not significant statistically.

Background Radiation↗

PubMed1998

Existence and uniqueness of endemic states for the age-structured S-I-R epidemic model.

The existence and uniqueness of positive steady states for the age structured S-I-R epidemic model with intercohort transmission is considered. Threshold results for the existence of endemic states are established for most cases. Uniqueness is shown in each case. Threshold used are explicitly computable in terms of demographic and epidemiological parameters of the model.

Age Factors↗

PubMed1997

Electrophysiologic Effects of the New Class III Antiarrhythmic Drug Dofetilide in an Experimental Canine Model of Pacing-induced Atrial Fibrillation.

BACKGROUND: Dofetilide is a new class III antiarrhythmic drug currently under investigation for the treatment of supraventricular arrhythmias in humans. Dofetilide have been previously shown to be highly effective in terminating and suppressing reentrant atrial flutter in the experimental canine crush-injury model, in which its antiarrhythmic efficacy was correlated with prolongation of wavelength and reduction in dispersion of refractoriness, effects not produced by the class IA antiarrhythmic drug quinidine. The purpose of this study was to evaluate the antiarrhythmic efficacy and mechanisms of action of dofetilide in an experimental model of atrial fibrillation. METHODS AND RESULTS: Dofetilide was administered intravenously to seven open-chest dogs with acute sustained atrial fibrillation induced by rapid atrial pacing for up to 4 hours. Mean atrial effective refractory period (ERP), dispersion of ERP, conduction velocity and wave-length were determined by multipoint right atrial programmed stimulation and activation mappin gusing a 56-electrode mapping plaque on the right atrial free wall. Dofetilide prolonged average ERP by 22% from 104 +/- 13 to 127 +/- 15 ms (P <.001), prolonged maximum ERP by 11% from 129 +/- 7 to 143 +/- 10 (P <.003), had no effect on conduction velocity at 200 ms pacing cycle length, slowed conduction velocity by 16% from 0.89 +/- 12 to 0.75 +/-.17 ms at 150 ms pacing cycle length, slowed conduction velocity by 16% from 0.89 +/- 12 to 0.75 +/-.17 ms at 150 ms pacing cycle length (P <.001), increased wavelength by 20% from 93 +/- 7 to 112 +/- 9 mm (P <.01), reduced dispersion of ERP by 24% from 11.4 +/- 2.9 to 8.7 +/- 2.3 (P =.016), and reduced the number of adjacent electrodes with ERP difference >/=20 ms by 67% from 18.4 +/- 7.1 to 6.1 +/- 4.2 (P <.001). Dofetilide reduced the number of excitation wavelets (total over three beats) entering the region of the mapping plaque by 38% from 5.0 +/-.8 to 3.1 +/-.4 (P <.002). Dofetilide terminated atrial fibrillation in all seven dogs at a mean of 3.4 +/- 2.2 minutes into the loading infusion and prevented reinduction of atrial fibrillation in all seven dogs after completion of the loading infusion, while on maintenance infusion. Time to termination of atrial fibrillation correlated closely with change in ERP (r = 0.78, P =.036). CONCLUSIONS: Dofetilide was highly effective in terminating and suppressing sustained pacing induced atrial fibrillation in this canine model. Time to termination of atrial fibrillation correlated with the degree of change in ERP produced by dofetilide. The mechanism of termination of atrial fibrillation by dofetilide appeared to be a progressive reduction and eventual extinction of re-entrant wavelets. The predominant electrophysiologic effects of dofetilide were prolongation of ERP and wavelength and a reduction in dispersion of refractoriness. Dofetilide had little effect on conduction velocity in this model, except at very short pacing cycle lengths.

Journal Article↗

PubMed1996

Stabilization of granulocyte colony-stimulating factor and structurally analogous growth factors by anionic phospholipids.

Recombinant granulocyte colony-stimulating factor (rhG-CSF) interacts with liposomes composed of the anionic phospholipid dioleoylphosphatidylglycerol (DOPG), and this interaction enhances the stability of the protein [Collins, D., & Cha, Y. (1994) Biochemistry 33, 4521-4526]. In the present studies, we have examined the interaction of rhG-CSF with phospholipids other than DOPG. Fluorescence spectroscopy of rhG-CSF with a variety of lipid vesicles demonstrated that rhG-CSF inserts into bilayers of anionic, but not zwitterionic, phospholipids. Isothermal titration calorimetry of the interaction between DMPG and rhG-CSF indicates that the binding is saturable and involves 10 lipids/rhG-CSF. Studies of phosphatidylglycerols with varying alkyl chain lengths determined that the stabilization of rhG-CSF by anionic phospholipids required a certain alkyl chain length; no stabilization was observed with lipids of shorter chain length. Also investigated was the stabilization of other growth factors, which are structurally similar to rhG-CSF, by anionic phospholipids. These proteins include recombinant porcine somatotropin (rpSt), recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), recombinant human interleukin 4 (rhIL-4), and recombinant human interleukin 2 (rhIL-2). The helical secondary structure of the proteins was recoverable after heating and cooling in the presence of anionic phospholipids as observed by circular dichroism; the presence of zwitterionic lipids did not induce this effect. Results of these investigations concluded that a group of structurally similar proteins interact preferentially with anionic phospholipids and that the complexation of the growth factors with vesicles composed of anionic phospholipids improves the stability of the proteins under conditions where they normally denature.

Calorimetry, Differential Scanning↗

PubMed1996

Electrophysiologic effects of the new class III antiarrhythmic drug dofetilide compared to the class IA antiarrhythmic drug quinidine in experimental canine atrial flutter: role of dispersion of refractoriness in antiarrhythmic efficacy.

INTRODUCTION: Previous studies suggest that class III antiarrhythmic drugs are more effective in reentrant arrhythmias because they prolong refractoriness (ERP) and wavelength and reduce dispersion of refractoriness compared to Class IA antiarrhythmic drugs, which slow conduction velocity (CV) in addition to their effects on refractoriness. METHODS AND RESULTS: To test this hypothesis, the Class III drug dofetilide and the Class IA drug quinidine were studied in the experimental canine crush-injury model of atrial flutter, utilizing right atrial multipoint programmed stimulation and activation mapping. In seven dogs dofetilide prolonged ERP by 23%, slowed CV by 9% at 200-msec cycle length (P < 0.001) and by 39% at 150-msec cycle length (P < 0.001), and increased wavelength by 11% (P < 0.02). Dofetilide reduced dispersion of ERP by 20% (P = 0.003) and adjacent electrodes with ERP difference > or = 20 msec by 76% (P < 0.001). Dofetilide slowed atrial flutter by 37% (P = 0.003) prior to terminating and suppressing it in all dogs. In eight dogs quinidine prolonged ERP by 14% (P < 0.001), slowed CV by 14% at 200-msec length cycle (P < 0.001) and by 19% at 150-msec cycle length (P < 0.001), and reduced wavelength by 2% (P = NS). Quinidine did not reduce dispersion of refractoriness. Quinidine slowed atrial flutter by 57% (P < 0.001), terminating and suppressing it in only three dogs. Efficacy of dofetilide was greater than quinidine (P = 0.026) and correlated with reduced dispersion of ERP (r = -0.653, P = 0.01), reduced adjacent electrodes with ERP difference > or = 20 msec (r = -0.637, P = 0.012), and prolonged wavelength (r = 0.61, P = 0.018). Dofetilide and quinidine terminated atrial flutter by similar mechanisms. Myocardial fiber orientation was nonuniform around the crush injury. CONCLUSIONS: Antiarrhythmic efficacy of dofetilide was greater than that of quinidine and correlated with drug-induced prolongation of wavelength and reduction in dispersion of refractoriness, effects produced only by dofetilide.

Action Potentials↗

PubMed1995

p53-independent induction of WAF1/CIP1 in human leukemia cells is correlated with growth arrest accompanying monocyte/macrophage differentiation.

The p53 tumor suppressor gene plays a role in controlling a G1 phase checkpoint. The WAF1/CIP1 gene with encodes p21WAF1/CIP1 protein, an inhibitor of cyclin-dependent kinases, is a downstream mediator of p53 function. We examined expression of the WAF1/CIP1 gene and its relationship to growth arrest and differentiation in p53-null human leukemic cell lines. We show that p53-independent induction of WAF1/CIP1 occurs in human leukemia cells treated with 12-O-tetradecanoylphorbol-13-acetate, okadaic acid, or IFN-gamma but not with retinoic acid, vitamin D3, or DMSO. Furthermore, WAF1/CIP1 induction correlates with growth arrest associated with monocyte-macrophage differentiation. The present studies support the idea that WAF1/CIP1 gene expression can be regulated through multiple mechanisms, suggesting that strategies may be designed to restore the G1 checkpoint controls in p53-null cells by targeting these p53-independent mechanisms of WAF1/CIP1 induction.

Blotting, Northern↗

PubMed1994

Interaction of recombinant granulocyte colony stimulating factor with lipid membranes: enhanced stability of a water-soluble protein after membrane insertion.

The interaction of recombinant granulocyte colony stimulating factor (rhG-CSF) with lipid vesicles was studied. In the presence of dioleoylphosphatidylglycerol (DOPG) vesicles, the intrinsic fluorescence of rhG-CSF exhibits dramatic changes. In particular, tryptophan fluorescence is greatly enhanced and the emission maximum shifted to lower wavelengths. The presence of DOPG vesicles causes the protein tryptophans to become inaccessible to iodide, a water-soluble quencher of tryptophan fluorescence, yet accessible to quenching via energy transfer to pyrenyl decanoic acid, a lipid-soluble fluorescent probe. The data suggest that rhG-CSF inserts into lipid vesicles composed of DOPG. The driving force for the insertion may be a conformational change induced by the low pH at the lipid-water interface of DOPG vesicles. The DOPG-inserted form of rhG-CSF retains biological activity and shows remarkable stability, even under high-temperature conditions which lead to denaturation of rhG-CSF alone. Membrane insertion of G-CSF may be involved in the in vivo activity of this important cytokine.

Decanoic Acids↗

PubMed1994

Human interferon regulatory factor 2 gene. Intron-exon organization and functional analysis of 5'-flanking region.

Interferon regulatory factor 2 (IRF-2) is a transcriptional regulatory protein that terminates interferon beta expression initiated by interferon regulatory factor 1. In this study, we isolated the genomic DNA for human IRF-2 gene, determined the intron-exon structure of the human IRF-2 gene, mapped the major transcription initiation site, identified a number of potential regulatory elements in the 5'-flanking region, and localized the IRF-2 gene on human chromosome 4. The IRF-2 promoter region contains a CpG island, with several GC boxes, a putative NF-kappa B-binding site, and a CAAT box, but no TATA box. When the promoter region was linked with a heterologous reporter gene, we found that the promoter region is inducible by both interferons (interferon-alpha and -gamma) and interferon regulatory factor 1. The region which induced these inductions was identified as being confined to 40 nucleotides 5' to the major transcriptional initiation site by testing a series of clones with truncated promoter of IRF-2. This region contains elements which are shared with the transcriptional enhancers of other genes including interferon regulatory factor 1, interferon beta, and interferon-inducible genes. These data suggest that interferon regulatory factor 1 not only triggers the activation of the interferon signal transduction pathway, but also may play a role in limiting the duration of this response by activating the transcription of IRF-2.

Amino Acid Sequence↗

PubMed1993

The motif Tyr-X-X-hydrophobic residue mediates lysosomal membrane targeting of lysosome-associated membrane protein 1.

We have investigated the mechanism by which LAMP-1, a principal protein of the lysosomal membrane, is targeted to lysosomes. Mutagenesis and transfection experiments indicate that the motif Tyr-X-X-hydrophobic residue at the carboxyl terminus of the 11-amino acid cytoplasmic tail of the protein constitutes the lysosomal targeting signal for LAMP-1. This motif directs CD44, a cell surface hyaluronate receptor, to the lysosomal membrane, but only when the signal is placed at the carboxyl-terminus of a truncated cytoplasmic tail. The signal did not confer lysosomal targeting when it was situated internally or at the carboxyl terminus of the normal CD44 cytoplasmic tail. An apparent paradox is that similar Tyr-containing sequences mediate internalization, but not lysosomal targeting, of several receptors. Of possible relevance is the additional finding that purified LAMP-1 protein lacks the two carboxyl-terminal residues predicted by cDNA, both of which are essential for proper trafficking. A model is proposed in which lysosomal targeting is distinguished from receptor internalization through proteolytic modification of the internalization signal.

Amino Acid Sequence↗

PubMed1993

Molecular approaches to the diagnosis and treatment of cancer.

We have used autologous bone marrow transplantation (ABMT) as a setting to develop the genetic therapy of cancer in hematopoietic neoplasms based on the use of the bone marrow as a conduit through which to introduce regulatory molecules into the patient. This has involved three developmental phases: 1) learning how to develop genetic modification techniques; 2) learning how to develop in vivo selection techniques for the genetically modified cells; and 3) developing molecular vectors for modification of hematopoietic cells for therapy of cancer. These programs will be summarized in terms of their progress at the conference.

Bone Marrow Transplantation↗

PubMed1993

A novel interferon-inducible domain: structural and functional analysis of the human interferon regulatory factor 1 gene promoter.

We have cloned and functionally characterized the human interferon regulatory factor 1 (IRF-1) gene promoter. The promoter contains a CpG island, with several GC boxes, a CAAT box, but no TATA box. IRF-1 mRNA is strongly induced by gamma interferon (IFN-gamma) but more weakly and transiently by IFN-alpha. There are several putative kappa B motifs and numerous AA(G/A)G(G/T)A and GAAANN motifs throughout the promoter. The IRF-1 promoter is not autoregulated by the IRF-1 gene product. IFN inducibility of the promoter was studied with 5' deletion mutants linked to a heterologous reporter gene. Gel mobility shift assays were used to show IFN-inducible factor binding to the IRF-1 promoter. These studies showed that IFN inducibility is conferred by a novel imperfect inverted-repeat arrangement of two GAAANN motifs within a domain, 130 nucleotides upstream of transcription initiation. This inverted repeat binds a factor upon induction with IFN and can confer IFN inducibility on a heterologous promoter. Conversely, point mutations of the inverted repeat are not IFN inducible when linked to the same heterologous promoter.

Base Sequence↗

PubMed1992

Role of internal thermodynamics in determining hydrogen tunneling in enzyme-catalyzed hydrogen transfer reactions.

Previous investigations have indicated a role for hydrogen tunneling in the yeast alcohol dehydrogenase catalyzed oxidation of benzyl alcohol [Cha, Y., Murray, C. J., & Klinman, J. P. (1989) Science 243, 1325] and the bovine plasma amine oxidase catalyzed oxidation of benzylamine [Grant, K.L., & Klinman, J. P. (1989) Biochemistry 28,6597]. In the present studies, values of protium to tritium and deuterium to tritium isotope effects and their temperature dependencies have been measured using ring-substituted substrates for yeast alcohol dehydrogenase and bovine plasma amine oxidase, revealing tunneling in each case. The results of these studies indicate that hydrogen tunneling is a general phenomenon and is not limited to enzyme reactions with degenerate energy levels for bound substrates and products. An analysis of internal thermodynamics in the yeast alcohol dehydrogenase reaction shows that tunneling occurs when delta H degrees is endothermic and that the degree of tunneling appears to increase as delta H degrees decreases toward zero.

Alcohol Dehydrogenase↗

PubMed1992

Human interferon regulatory factor 1: intron-exon organization.

Interferon (IFN) regulatory factor 1 (IRF-1) is a transcriptional regulatory protein that mediates the transcriptional activation of the IFN-alpha and IFN-beta genes by viruses and IFNs. To characterize the mechanisms that govern the level of IRF-1 in cells, we isolated the IRF-1 gene and characterized the structure of its intronic and exonic domains and of its regulatory promoter region. A human placental genomic library was screened with an IRF-1 cDNA probe, and two clones that contained the IRF-1 gene and its 5' regulatory region were obtained. We used these clones to determine the complete nucleotide sequence for the IRF-1 gene, finding that the IRF-1 gene spanned 7.72 kb of DNA and included 10 exons and 9 introns. When the deduced amino acid sequences were compared among different species, the most conserved exons were exons 2, 3, and 4, in which the putative DNA binding domain for the IRF-1 protein is located.

Amino Acid Sequence↗

PubMed1992

Energy storage of linear and cyclic electron flows in photosynthesis.

The energy storage of photosynthesis in the green alga Chlorella vulgaris was determined by pulsed, time-resolved photoacoustics. The energy storage of the linear electron transfer process in photosynthesis, of cyclic photosystem (PS) I, and possibly of PSII was determined by selection of excitation wavelength and of flash interval. At 695 nm excitation, a rather large cyclic PSI energy storage of 0.68 +/- 0.04 eV/quantum of energy at 8 ms after a 1-mus flash was obtained. This energy remained the same at flash intervals of 0.35 to 60 s and was independent of the presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea. We tentatively assign this energy to the ferredoxin-NADP-reductase-ferredoxin and oxidized cytochrome b(6)/f complexes. An efficient distribution of energy between cyclic and linear systems is obtained with the simple assumption that the turnover time of the cyclic system is slower than that of the linear system. The energy storage of linear electron flow was determined by 655 nm excitation of Chlorella with a short flash interval of 0.35 s per flash. It was calculated to be 0.50 +/- 0.03 eV/hv, close to that expected for oxygen and NADPH formation. The energy storage of PSII is determined by excitation of Chlorella at 655 nm with a long flash interval of 60 s per flash. It was calculated to be 1.07 +/- 0.05 eV/hv, consistent with the energy storage being in S-states and the secondary electron acceptor of PSII with a calculated redox energy of 1.03 eV/hv. In the presence of 1 mum 3-(3,4-dichlorophenyl)-1,1-dimethylurea, the calculated energy storage in PSII is still significant, 0.53 +/- 0.04 eV/hv. This probably indicates a significant cyclic electron flow around PSII. These cyclic flows may contribute considerably to energy storage in photosynthesis.

Journal Article↗

PubMed1990

The cDNA sequence of mouse LAMP-2. Evidence for two classes of lysosomal membrane glycoproteins.

We describe the isolation and sequencing of a cDNA encoding the mouse lysosomal membrane glycoprotein mLAMP-2 and the sequence differences that distinguish this molecule from the LAMP-1 class of proteins. An oligonucleotide probe corresponding to the NH2-terminal amino acid sequence of purified mLAMP-2 was synthesized by the polymerase chain reaction and used to screen several cDNA libraries. cDNA clones with an insert of 1,700 nucleotides were identified and sequenced. The deduced amino acid sequence of mLAMP-2 comprises a signal sequence of 25 residues and a 390-amino acid polypeptide (Mr 43,017) with the following putative domains: a large intraluminal region (residues 1-354) with 17 N-linked glycosylation sites (Asn-X-Ser/Thr), a hydrophobic transmembrane-spanning region of 24 residues (355-378), and a COOH-terminal cytoplasmic tail of 12 residues (379-390). When this sequence is compared with those of other lysosomal membrane glycoproteins, it is apparent that mouse LAMP-2 and human LAMP-2 form one homology class (LAMP-2) that is separated from the LAMP-1 class of proteins. The sequence differences in these two classes provide a basis for comparing the structure of the proteins with their biochemical and biological properties.

Amino Acid Sequence↗

PubMed1990

The biodegradability of polyester blends.

Blends of poly(epsilon-caprolactone) (PCL) and poly(L-lactic acid) (PLLA) with polyglycolic acid-co-L-lactic acid (PGLA) were prepared by three methods: compression moulding, coprecipitation, and solvent evaporation of a methylene chloride-in-water emulsion of the polymers. The rates of hydrolytic chain scission of each component of the blends were determined by deconvolution of GPC traces of samples maintained in phosphate buffer, pH 7.4, 37 degrees C, for up to 3000 h. The observed rates were dependent on the method of blending. For compression moulded blends, the rate of chain scission of PGLA was decreased and that of PCL and PLLA increased. A corresponding delay in the onset of weight loss was also observed. There was no evidence of blend miscibility.

Biodegradation, Environmental↗

PubMed1989

Hydrogen tunneling in enzyme reactions.

Primary and secondary protium-to-tritium (H/T) and deuterium-to-tritium (D/T) kinetic isotope effects for the catalytic oxidation of benzyl alcohol to benzaldehyde by yeast alcohol dehydrogenase (YADH) at 25 degrees Celsius have been determined. Previous studies showed that this reaction is nearly or fully rate limited by the hydrogen-transfer step. Semiclassical mass considerations that do not include tunneling effects would predict that kH/kT = (kD/kT)3.26, where kH, kD, and kT are the rate constants for the reaction of protium, deuterium, and tritium derivatives, respectively. Significant deviations from this relation have now been observed for both primary and especially secondary effects, such that experimental H/T ratios are much greater than those calculated from the above expression. These deviations also hold in the temperature range from 0 to 40 degrees Celsius. Such deviations were previously predicted to result from a reaction coordinate containing a significant contribution from hydrogen tunneling.

Alcohol Dehydrogenase↗