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Biomedical subjects

Y Cho

Publications and source records attributed to Y Cho.

At least 145 records · Page 8Linked to original sources
PubMed1993

Crystal structure of adenylosuccinate synthetase from Escherichia coli. Evidence for convergent evolution of GTP-binding domains.

The structure of the P2(1) crystal form of adenylosuccinate synthetase from Escherichia coli has been determined to a resolution of 2.8 A. The refined model for the enzyme gives an R factor of 0.20 and a root-mean-square deviation from expected bond lengths and angles of 0.016 A and 2.27 degrees, respectively. The dominant structural element of each monomer of the homodimer is a central beta-sheet of 10 strands. The first nine strands of the sheet are mutually parallel with right-handed crossover connections between the strands. The 10th strand is antiparallel with respect to the first nine strands. In addition, the enzyme has two antiparallel beta-sheets, comprised of two strands and three strands each, 11 alpha-helices and two short 3/10-helices. The overall fold of the polypeptide chain has not been observed heretofore in any other protein structure. Residues tentatively assigned to the active site of the enzyme on the basis of chemical modification and directed mutation cluster in two separate regions. Gly12, Gly15, Gly17, Lys18, Ile19, and Lys331 lie at one end of a crevice that measures 12 A by 30 A by 12 A deep. Lys140 and Arg147 are not part of this crevice, but instead lie at the interface between monomers of the dimer. Lys140 makes a salt link with Asp231 of a monomer related by molecular symmetry and Arg147 binds to the carbonyl of the same Asp231. Superposition of the p21 ras protein (Pai, E. F., Kabsch, W., Krengel, U., Holmes, K., John, J., and Wittinghofer, A. (1989) Nature 341, 209-214) onto the synthetase reveals significant correspondences between side chains of the two proteins. Residues which interact with GTP in the p21ras protein have structurally equivalent residues in the synthetase. The GTP molecule, when transformed to the coordinate frame of the synthetase, falls into the crevice defined by studies in directed mutation. We suggest that the similarities in the GTP-binding domains of the synthetase and the p21ras protein are an example of convergent evolution of two distinct families of GTP-binding proteins.

Adenylosuccinate Synthase↗
PubMed1993

The progression of retinopathy of prematurity and fluctuation in blood gas tension.

In this study, the relationship between the fluctuation in blood oxygen and carbon dioxide tension and the progression of acute retinopathy of prematurity (ROP) was evaluated. Eighteen extremely premature infants were selected on the basis of the following criteria: gestational age less than 26 weeks, oxygen supply or mechanical ventilation for more than 50 days, transcutaneous oxygen pressure (TcPO2) recorded almost once per hour, and arterial oxygen pressure (PaO2) and arterial carbon dioxide pressure (PaCO2) measured intermittently, for over 8 weeks after birth. All of these infants developed ROP, which ceased progressing in 7 infants (group I, stage 1 or 2 ROP, international classification), but advanced in 11 (group II, stage 3 or 3+). The fluctuations in TcPO2, PaO2, and PaCO2 are represented as coefficients of both variation (CV) and mean difference (D) in these two groups. The results demonstrate that both the CV and D values of TcPO2 are significantly elevated in group II infants compared with group I infants, in the first and second 3-weeks periods, and over the entire 9-week period after birth. The incidences of extreme hyperoxemia (TcPO2 > or = 100 mm Hg) and hypoxemia (TcPO2 < 30 mm Hg) in recorded TcPO2 time series show no significant differences between these two groups. We conclude that extremely premature infants with widely fluctuating arterial oxygen tension may have a greater chance of developing progressive ROP.

Blood Gas Monitoring, Transcutaneous↗
PubMed1993

Vasovasostomy in rabbits using fibrin adhesive prepared from a single human source.

We were interested in determining whether fibrin glue derived from a single human source could be used effectively to produce a sutureless vasovasostomy in the rabbit model. Fifteen rabbits were divided into two groups (7 control, 8 experimental) and underwent vasal transection and reanastomosis by conventional microsurgical suture techniques (control group) and sutureless anastomosis using single source fibrin glue (experimental group). The patency and tensile strength of the anastomoses were compared at four weeks and the anastomotic sites underwent histologic examination. This study demonstrated that a vasovasal anastomosis in the rabbit could be achieved using human single source fibrin glue with patency equivalent to a standard sutured anastomosis. The tensile strength of the glued anastomosis at four weeks was greater than the tensile strength of the sutured anastomosis.

Animals↗
PubMed1993

2D 1H and 31P NMR spectra and distorted A-DNA-like duplex structure of a phosphorodithioate oligonucleotide.

Assignment of the 1H and 31P NMR spectra of a phosphorodithioate modified oligonucleotide decamer duplex, d(CGCTTpS2-AAGCG)2 (10-mer-S; a site of dithioate substitution is designated with the symbols pS2-), was achieved by two-dimensional homonuclear TOCSY, NOESY and 1H-31P Pure Absorption phase Constant time (PAC) heteronuclear correlation spectroscopy. In contrast to the parent palindromic decamer sequence (1) which has been shown to exist entirely in the duplex B-DNA conformation under comparable conditions (100 mM KCl), the dithiophosphate analogue forms a hairpin loop. However, the duplex form of the dithioate oligonucleotide can be stabilized at lower temperatures, higher salt and strand concentration. The solution structure of the decamer duplex was calculated by an iterative hybrid relaxation matrix method (MORASS) combined with 2D NOESY-distance restrained molecular dynamics. These backbone modified compounds, potentially attractive antisense oligonucleotide agents, are often assumed to possess similar structure as the parent nucleic acid complex. Importantly, the refined structure of the phosphorodithioate duplex shows a significant deviation from the parent unmodified, phosphoryl duplex. An overall bend and unwinding in the phosphorodithioate duplex is observed. The structural distortion of the phosphorodithioate duplex was confirmed by comparison of helicoidal parameters and groove dimensions. Especially, the helical twists of the phosphorodithioate decamer deviate significantly from the parent phosphoryl decamer. The minor groove width of phosphorodithioate duplex 10-mer-S varies between 8.4 and 13.3 A which is much wider than those of the parent phosphoryl decamer d(CGCTTAAGCG)2 (4.2 approximately 9.4 A). The larger minor groove width of 10-mer-S duplex contributes to the unwinding of the backbone and indicates that the duplex has an overall A-DNA-like conformation in the region surrounding the dithiophosphate modification.

Base Sequence↗
PubMed1993

Thirty-year trends in clinical kidney transplantation.

Trends in one-year graft survival rates seen in the past 30 years were examined in the UCLA and UNOS Registries. Some of the trends noted were as follows: 1. One-year graft survival rates for cadaver-donor transplants improved from 40% to 80% during this 30-year period. One-year patient survival improved from 50% to 95%. Transplants from living-related donors improved in graft survival from 80% to 90-95%. 2. Factors that diminished in importance were: recipient race, sensitization, primary disease, HLA haplotype matching in living donors, recipient and donor sex, kidney sharing, and transfusions. 3. Factors that continue to provide about a 10% variation of one-year graft survival are: cold ischemia time, HLA mismatch, recipient and donor age. 4. Posttransplantation, factors such as first-day diuresis, one-week dialysis, rejection at discharge, and discharge serum creatinine continue to be very important determinants of future outcome in 6 yearly subsets of patients. 5. Induction by ALG and OKT3 was shown in 6 subsets to have no effect on one-year graft survival. 6. Future trend studies will be needed to examine the 5-year long-term effects.

Adolescent↗
PubMed1991

HLA matching: univariate and multivariate analyses of UNOS Registry data.

1. Black transplant recipients showed little or no matching effect when HLA-A, B, and DR antigens matched. This may have been due in part to differences in serologically defined antigens found in Black populations. 2. There was a statistically significant (p less than 0.001 for best vs worst match) matching effect in White transplant recipients that occurred at 3 months following grafting and continued through 3 years follow-up. These patients had better graft survival for both 5 and 6, compared to 3 and 4, or as compared to 0-, 1-, and 2-match transplants; the corollary groups for mismatched transplants were also significantly different. At 3 years, there was a 20% difference in graft survival from the best- to the worst-matched transplants. Earlier this difference was 7-10% but significantly different. 3. When the HLA Class I parent antigens as defined in the Materials and Methods section were eliminated, there was an increase in graft survival for the best-matched transplants. This was postulated to occur because of better matching obtained by matching the well-defined HLA specificities. 4. With hierarchy matching, possibly there was a stronger effect of matching HLA Class II antigens at 3 months; however, this effect was quickly lost at 1 and 3 years, and data that support early graft survival advantages by matching Class II antigens were inconclusive. Most importantly, there was a threshold matching effect that showed transplant recipients with 4 or more HLA matches or 2 or less mismatches had significantly better short- and long-term outcome than the poorer-matched groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

UCLA and UNOS Registries. Overview.

The subjects of this study were transplant recipients entered in the UCLA Registry file since 1984 and in the UNOS Registry since 1987. [table: see text] 5. Based on the data above, we conclude that the near 20% loss rate in the first year can be roughly allocated as follows: death 3%, technical 3%, agonal kidney damage 6%, and histocompatibility differences 7%. 6. The quality of HLA typing was assessed by examining the frequencies of the various specificities reported for cadaver donors in 8 yearly periods from 1984 to 1991. The A and B loci specificities were remarkably constant. The DR specificities were still undergoing stabilization. 7. No urine output on the first day, which occurred in approximately 10% of the first cadaver-donor transplants, resulted in about a 20 percentage point lower graft survival rate at 1 year. 8. Anuria on the first day increased with cold ischemia time, donor age, cerebral vascular accident donors, and retransplant recipients. 9. Graft survival with anuria on the first day and: [table: see text] 10. When dialysis was required during the first week, there was an approximate 15 percentage point decrease in 1-year graft survival in 25% of the patients. 11. One rejection in the first hospitalization period resulted in 67% 1-year graft survival. More than 1 rejection led to 57% 1-year graft survival. 12. Serum creatinine at discharge was an accurate indicator of subsequent graft survival. Approximately a 7 percentage point drop in 1-year graft survival was noted with each unit of serum creatinine above 2.0 mg/dl.

Adolescent↗
PubMed1991

A report from the UNOS Scientific Renal Transplant Registry.

The UNOS Kidney Transplant Registry is now fully operational. Aside from scientific reports from UCLA, analysis of the same data base from investigators who initiate projects through UNOS central in Richmond, as well as from HICFA and USRDS, can be anticipated. Plans are underway to simplify the reporting process. With the large number of accumulated cases, it should be possible to analyze many factors in the future. Presently, histocompatibility differences in living related vs cadaver donors and degrees of HLA mismatching among recipients of cadaveric kidneys are major factors. Immunization by transplant rejection is the second most important factor.

Graft Survival↗
PubMed1990

Uptake of glutamate and cysteine in C-6 glioma cells and in cultured astrocytes.

The uptake of glutamate in rat glioma C-6 cells and cultured astrocytes derived from rat cerebral hemispheres was found to be mediated by a Na(+)-dependent and a Na(+)-independent system. The Na(+)-dependent system was inhibited by aspartate and was consistent with the commonly occurring system designated system X-AG. The Na(+)-independent system was inhibited by cystine and was consistent with system x-c described in various types of cells in the periphery. It was also found that quisqualate selectively and competitively interfered with the Na(+)-independent glutamate uptake. In C-6 cells, the glutamate uptake via systems X-AG and x-c accounted for approximately 35% and 55% of the total uptake, respectively, at 0.05 mM glutamate. In cultured astrocytes, the glutamate uptake via system X-AG was very potent, whereas the uptake via system xc- was relatively weak and its contribution to the total uptake of glutamate seemed almost negligible. However, in both C-6 cells and astrocytes, system xc- was necessary for the uptake of cystine, another substrate of system xc-. Cystine in the culture medium was an essential precursor of glutathione, and the inhibition of the cystine uptake by excess glutamate as a competitor led to a severe deficiency in glutathione, followed by cell degeneration.

Amino Acids↗
PubMed1989

Endothelial attachment and plasmalemmal apposition in the transcellular movement of intravascular leukemic cells entering the myeloid parenchyma.

The plasmalemmal relationship between metastases-forming leukemia cells and myeloid sinus endothelium during the transmural passage of the leukemia cells has been studied in rat bone marrow. After the myeloid vascular system was freed from normal circulating blood cells, the bone marrow was perfused with a suspension of leukemia cells derived from an ascites tumor. The bone marrow was then fixed by perfusion with double aldehyde with and without the addition of tannic acid. Leukemia cells were seen adhering to the adluminal aspect of the sinus endothelium and in all stages of endothelial penetration. The penetration of the sinus wall was independent of endothelial junctions; i.e., the transmural passage into the myeloid parenchyma was transcellular. At these sites, there were restricted areas of close plasmalemmal appositions of the two cell types where the intraplasmalemmal space was reduced to 2.3 nm. This space was interrupted by electron densities of 5 nm diameter and spaced 9 nm center to center. These close plasmalemmal appositions extended over distances ranging from 150 nm to 200 nm. It is suggested on the basis of the structural similarity that these heptalaminar complexes of close plasmalemmal apposition represent the structural equivalent of gap junctions and may be sites of intercellular communication requisite for transmural passage. When tannic acid was added to the fixative, there were extended areas of apparent fusion of the plasmalemmas of the two cell types, at the sites both of adhesion and of endothelial penetration. This fusion was limited to the outer leaflets of the two plasmalemmas, resulting in a single pentalaminar complex. These pentalaminar complexes extended over decidedly longer distances than the presumed gap junctions seen in the nontannic-acid-fixed material. The tannic acid material did not show the heptalaminar gap junction type of plasmalemmal apposition. It is believed likely that the tannic-acid-induced pentalaminar complexes may incorporate the smaller heptalaminar ones. The factors underlying the plasmalemmal configurational differences between the tannic acid and non-tannic-acid material remain undetermined.

Animals↗
PubMed1989

The UNOS Scientific Renal Transplant Registry.

1. After 2 years of data collection and compiling, the UNOS Scientific Renal Transplant Registry was analyzed for the first time. One-year graft survival rates were 89% for first parent donor transplants (257), 76% for first cadaver (7,049), 65% for second cadaver (1,072), and 57% for multiple retransplant recipients (221). 2. The side-by-side comparison of the UNOS and UCLA registries revealed a remarkable similarity between results from the 2 databases. The concordance between the registries makes us confident in the validity of the UNOS data and also suggests that centers submitting data to the voluntary UCLA Registry are representative of the national experience. 3. Eighty-nine recipients of 6-antigen matched first cadaver transplants were identified in the UNOS Registry with 88% graft survival at 1 year. This result is comparable to that obtained from surveys that identified 224 recipients with 90% graft survival at 1 year. These results underscore the importance of sharing cadaver kidneys to achieve perfectly matched transplants. 4. Blood transfusions improved graft survival by 5% at 1 year. More than one-quarter of the first cadaver transplant recipients were nontransfused. 5. The first follow-up report after discharge of the transplant recipient was requested at 6 months by UNOS. This delay in reporting transplant outcome resulted in a serious lag between the time a transplant was performed and its availability for analysis. The UCLA Registry collects a report at 3 months and had more recent transplants available for analysis.

Databases, Bibliographic↗