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Biomedical subjects

H Park

Publications and source records attributed to H Park.

At least 271 records · Page 15Linked to original sources

Diagnosis-related group refinement with diagnosis- and procedure-specific comorbidities and complications.

Diagnosis-related groups have been revised through more refined uses of secondary diagnoses. Under the refined diagnosis-related groups, patients are distinguished with respect to classes of secondary diagnoses that are disease- and procedure-specific. Each class represents a different level of utilization for a given principal diagnosis or surgical procedure. The refined system was evaluated with national data from the Medicare program. Estimates of hospital costs and utilization based on refined diagnosis-related groups were more precise than those based on unrefined diagnosis-related groups. This approach to diagnosis-related group refinement does not represent a radical departure from the current diagnosis-related group framework and does not require new data collection efforts. Moreover, a payment system based on the refined model is less affected by the ordering of the diagnoses than under the existing diagnosis-related group system. How the refined diagnosis-related group framework can accommodate future refinements at all levels of the classification scheme is also discussed.

Adult↗

Cytotoxicity of a cysteine proteinase of adult Clonorchis sinensis.

To clarify the correlation of the proteinase activity with pathogenicity of Clonorchis sinensis, the proteinase activity either in excretory-secretory products (ESP) or in crude extracts of adult C. sinensis was examined. Substrate gel electrophoresis of the ESP and crude extracts revealed four distinct enzyme bands, which were differently inhibited by the specific proteinase inhibitors. The proteinase of the ESP with molecular mass of 24 kDa, was purified 23-fold with 14.5% yield by spectra gel ACA 44 gel filtration. It exhibited optimal pH at 7.5 in sodium phosphate (0.1 M). Its activity was inhibited specifically by N-ethylmaleimide (NEM) and antipain whereas potentiated 1.9 folds in the presence of 5 mM dithiothreitol (DTT). Cytotoxicity of the proteinase increased in a dose-dependent manner up to 120 micrograms/ml while reduced by NEM and antipain, indicating that cysteine proteinase was responsible for the cytotoxicity. This result shows that the 24 kDa cysteine proteinase is deeply correlated with the pathogenicity of C. sinensis infection.

Animals↗

Synthesis of a photoaffinity taxol analogue and its use in labeling tubulin.

A photoaffinity analogue of taxol, N-([3,5-3H]-4-azidobenzoyl)-N-debenzoyltaxol (7), was synthesized and used to photolabel microtubules. Approximately 20% of the noncovalently bound analogue becomes covalently bound upon irradiation at 300 nm. Incorporated label was stable to a 50% ethanol solution and sodium dodecyl sulfate. About 80% of the incorporated label was found in the beta-subunit and 20% in the alpha-subunit. Incorporation did not occur into unpolymerized tubulin, consistent with the fact that taxol binds only to polymerized tubulin, and was decreased by the presence of taxol. Little or no nonspecific labeling occurs. This analogue is currently being used to identify taxol binding site(s) on tubulin.

Affinity Labels↗

TAR RNA-binding protein is an inhibitor of the interferon-induced protein kinase PKR.

A cDNA encoding a double-stranded-RNA (dsRNA)-binding protein was isolated by screening a HeLa cell cDNA expression library for proteins that bind the HIV-1 Rev-responsive-element RNA. The cDNA encoded a protein that was identical to TRBP, the previously reported cellular protein that binds the transactivation response element (TAR) RNA of human immunodeficiency virus type 1. TRBP inhibited phosphorylation of the interferon-induced ribosome-associated protein kinase PKR and of the eukaryotic translation initiation factor eIF-2 alpha in a transient-expression system in which the translation of a reporter gene was inhibited by the localized activation of PKR. TRBP expression in HeLa cells complemented the growth and protein-synthesis defect of a vaccinia virus mutant lacking the expression of the dsRNA-binding protein E3L. These results implicate TRBP as a cellular regulatory protein that binds RNAs containing specific secondary structure(s) to mediate the inhibition of PKR activation and stimulate translation in a localized manner.

Animals↗

Characterization of the gene encoding the human transcriptional elongation factor TFIIS.

The transcriptional elongation factor TFIIS causes stimulation of RNA polymerase II elongation and readthrough of some of the elongation blocks. We present cloning and sequence characterization of the human TFIIS gene and a pseudogene. The intron-less organization of both of these genes indicates that previously identified cDNAs which suggested the presence of an intron were the products of cloning artifacts. The gene is organized in an uninterrupted ORF which codes for 301 amino acids, whereas the pseudogene lacks an ORF able to code for a full-length protein. The potential promoter for the gene has two putative GC-box-type consensus sequences, two CCAAT-box consensus sequences, and is bounded by a human Alu sequence. Two potential transcriptional termination signal sequences downstream from the consensus polyadenylation signal are proposed.

Base Sequence↗

Ocular and optic nerve hemorrhages in abused infants with intracranial injuries.

PURPOSE: To ascertain whether the pathology of the eye and optic nerve might be useful in determining the manner of death in infants who died after sustaining apparent nonaccidental intracranial injury. METHODS: Complete autopsies were performed on 13 infants who died of acute intracranial injuries after nonaccidental trauma. The infants were divided into two groups: nine with physical evidence of blunt trauma to the head, and four without detectable scalp or skull injury whose intracranial injuries were attributed to violent shaking (shaken baby syndrome). Six infants with no intracranial injuries who died suddenly from unidentifiable causes (the so-called sudden infant death syndrome) served as controls. RESULTS: Optic nerve sheath hemorrhage, most prominent in the subdural space, was present in all 13 infants with nonaccidental intracranial injury. Multilayered retinal hemorrhage was present in at least one eye of 11 of these 13 infants. The location and quantity of the intraocular and optic nerve sheath hemorrhages did not differ in those with external head trauma and those without scalp or skull lesions. A single control infant had a few erythrocytes in the nerve fiber layer of the anterior optic nerve of one eye. The remainder of the control infants did not have evidence of hemorrhage in the eye or optic nerve sheath. CONCLUSION: Histopathologic analysis of optic nerve sheath and intraocular hemorrhages may be helpful in distinguishing traumatic from non-traumatic causes of death in infants.

Battered Child Syndrome↗

Investigation of vibration characteristics of the ligamentous lumbar spine using the finite element approach.

A nonlinear, three-dimensional finite element model of the ligamentous L4-S1 segment was developed to analyze the dynamic response of the spine in the absence of damping. The effects of the upper body mass were simulated by including a mass of 40 kg on the L4 vertebral body. The modal analyses of the model indicated a resonant frequency of 17.5 Hz in axial mode and 3.8 Hz in flexion-extension mode. Accordingly, the predicted responses for the cyclic load of -400 +/- 40 N applied at four different frequencies (5, 11, 16.5, and 25 Hz) were compared with the corresponding results for axial compressive static loads (-360, and -440 N). As compared to the static load cases, the predicted responses were higher for the cyclic loading. For example, the effect of cyclic load at 11 Hz was to produce significant changes (9.7-19.0 percent) in stresses, loads transmitted through the facets, intradiscal pressure (IDP), disk bulge, as compared to the static load predictions. The responses were found to be frequency dependent as well; supporting the in vivo observations of other investigators that the human spine has a resonant frequency. For example, the 11 Hz model (DYN11) compared to the DYN5 model showed an increase in majority of the predicted parameters. The parameters showed an increase with frequency until 17.5 Hz (resonant frequency of the model); thereafter a decrease at 25 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomechanical Phenomena↗

Fission yeast with DNA polymerase delta temperature-sensitive alleles exhibits cell division cycle phenotype.

DNA polymerases alpha and delta are essential enzymes believed to play critical roles in initiation and replication of chromosome DNA. In this study, we show that the genes for Schizosaccharomyces pombe (S.pombe) DNA polymerase alpha and delta (pol alpha+ and pol delta+) are essential for cell viability. Disruption of either the pol alpha+ or pol delta+ gene results in distinct terminal phenotypes. The S.pombe pol delta+ gene is able to complement the thermosensitive cdc2-2 allele of Saccharomyces cerevisiae (S.cerevisiae) at the restrictive temperature. By random mutagenesis in vitro, we generated three pol delta conditional lethal alleles. We replaced the wild type chromosomal copy of pol delta+ gene with the mutagenized sequence and characterized the thermosensitive alleles in vivo. All three thermosensitive mutants exhibit a typical cell division cycle (cdc) terminal phenotype similar to that of the disrupted pol delta+ gene. Flow cytometric analysis showed that at the nonpermissive temperature all three mutants were arrested in S phase of the cell cycle. The three S.pombe conditional pol delta alleles were recovered and sequenced. The mutations causing the thermosensitive phenotype are missense mutations. The altered amino acid residues are uniquely conserved among the known polymerase delta sequences.

Alleles↗

Ligand binding induces an asymmetrical transmembrane signal through a receptor dimer.

Two ligand (aspartate)-binding pockets are formed at the interface between the subunits of the Tar homodimer, a bacterial chemoreceptor. Using mutant heterodimers of a hybrid receptor, Taz1, which consists of the external domain of Tar and the cytoplasmic domain of EnvZ, we disrupted either one or the other of the two ligand-binding pockets. We found that occupation of only one of the ligand-binding pockets was sufficient for induction of a transmembrane signal, and that the subunit responsible for the binding of the amino group of the ligand transduces the signal.

Bacterial Outer Membrane Proteins↗