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Biomedical subjects

Y H Shin

Publications and source records attributed to Y H Shin.

At least 19 recordsLinked to original sources

Detection of hepatitis A virus from clotting factors implicated as a source of HAV infection among haemophilia patients in Korea.

To investigate the causal relationship of blood clotting factors and hepatitis A virus (HAV) infection in haemophilia patients during 1998-1999 in Korea, we performed a 1:3 matched case-control study and molecular detection of HAV from clotting factors and patients. The epidemiological investigation showed that one lot of clotting factor VIII was related epidemiologically to patients with hepatitis A with an odds ratio of 35.0, or 38.4 when adjusted for the interval between injections. We examined 17 sera collected from seven patients and 124 lots of blood clotting factors (factor VIII and factor IV) by HAV reverse transcriptase-polymerase chain reaction (RT-PCR). HAV RNA was detected in five clotting factors and six sera. The HAV sequence of one of the factor VIII samples was identical to the sequences found in three patients' sera. Findings from the laboratory and epidemiological studies suggested that the clotting factor was causally related to HAV infection in three haemophilia patients.

Adolescent↗

Superimposition of nutcracker syndrome in a haematuric child with Henoch-Schönlein purpura.

We report a child with Henoch-Schönlein purpura (HSP) who had shown persistent microscopic haematuria for 26 months and was found to have nutcracker syndrome by renal Doppler ultrasound. Haematuria subsided in accordance with radiological improvement of nutcracker syndrome. These findings suggest that the origin of urinary abnormalities in patients with HSP may not always be due to the renal involvement of vasculitis.

Child↗

Role of mesangial fibrinogen deposition in the pathogenesis of crescentic Henoch-Schonlein nephritis in children.

AIMS: To clarify the role of mesangial fibrinogen deposition in crescentic Henoch-Schönlein nephritis (HSN). METHODS: A retrospective analysis of 21 children with HSN treated with immunosuppressants. Serial renal biopsies were performed before and after treatment. They were divided into two groups according to the immunofluorescent course of fibrinogen deposition: group I (n = 9), no or decreased deposition; group II (n = 12), persistent or increased deposition. RESULTS: There were no differences between the two groups in renal manifestations or laboratory and histological findings at presentation. However, the activity index after immunosuppressive treatment was significantly decreased in group I (mean, 7.9 (SEM, 0.7) v 2.9 (0.4); p = 0.008) and unchanged in group II (mean, 6.8 (SEM, 0.3) v 6.0 (2.1)). The chronicity index was unchanged in group I, but increased in group II (mean, 0.8 (SEM, 0.3) v 1.8 (0.3); p = 0.02). Univariate analysis revealed that the only factor significantly related to persistent or increased fibrinogen deposition was age more than 9 years (p = 0.03). Furthermore, the intensity of fibrinogen deposition at the second biopsy correlated positively with the age at onset (R2= 0.306; p = 0.009) and changes in the percentage of crescents (post-treatment crescents (%) minus pretreatment crescents (%)) correlated positively with the intensity of fibrinogen deposition at the second biopsy (R2= 0.193; p = 0.046). CONCLUSIONS: This study indicates that fibrinogen deposition has an important role to play in renal injury of crescentic HSN and reflects persistent severe histological activity.

Age of Onset↗

Differences in p53 gene polymorphisms between Korean schizophrenia and lung cancer patients.

The reduced incidence of cancer observed in schizophrenia patients may be related to differences in genetic background. It has been suggested that genetic predisposition towards schizophrenia is associated with reduced vulnerability to lung cancer, and p53 gene is one of the candidate genes. We tested the genetic association between schizophrenia and lung cancer by analyzing polymorphic sites in the p53 gene. Genotype and allele frequencies at two polymorphic sites in the p53 gene (BstUI and MspI restriction sites in exon 4 and intron 6, respectively) were studied in Korean schizophrenia (n=179) and lung cancer patients (n=104). Comparisons of the genotype and allele frequencies of the MspI polymorphism revealed significant differences between schizophrenia and lung cancer patients. The results suggest that the p53 polymorphism specifically found in schizophrenia patients may be associated with reduced vulnerability to lung cancer.

Adult↗

Proteolytic enzyme conjugated to SC-glucan as an enzymatic transdermal drug penetration enhancer.

The objective of this study was to investigate the effect of papain, a proteolytic enzyme, on the percutaneous absorption of drugs. To guarantee the enzyme stability during the skin penetration, papain was modified by the conjugation to SC-glucan. The enhancing activity of drug penetration was evaluated using antipyrine and indomethacin as hydrophilic and hydrophobic model drugs, respectively. The SC-glucan-papain conjugate was found to be very effective for facilitating the percutaneous absorption of antipyrine. Microscopic observations showed that the thickness of stratum corneum and viable epidermis was increased by the treatment of the SC-glucan-papain conjugate. Moreover, it induced phase separation, lacuna formation, and lamellar disruption within the stratum corneum interstices. These structural changes by the SC-glucan-papain conjugate are likely to be induced from hydrolysis of extensive crosslinking of corneocyte envelopes and intracellular proteins. However, the SC-glucan-papain conjugate showed no skin irritation according to the Draize test, which may be due to the difficulty of the SC-glucan-papain conjugate in penetrating into the skin.

Administration, Cutaneous↗

Lyapunov instability of rigid diatomic molecules in three dimensions.

We study the Lyapunov instability of a three-dimensional fluid composed of rigid diatomic molecules by molecular dynamics simulation. We use center-of-mass coordinates and angular variables for the configurational space variables. The spectra of Lyapunov exponents are obtained for 32 rigid diatomic molecules interacting through the Weeks-Chandler-Andersen potential for various bond lengths and densities. We show the general trends and characteristic features of the spectra of the Lyapunov exponents, and discuss the different contributions between translational and rotational degrees of freedom depending on the density and the bond length from the calculation of the projection of a certain subspace of the tangent space vectors.

Journal Article↗

Characterization and regulation of Schizosaccharomyces pombe gene encoding thioredoxin.

A cDNA coding thioredoxin (TRX) was isolated from a cDNA library of Schizosaccharomyces pombe by colony hybridization. The 438 bp EcoRI fragment, which was detected by Southern hybridization, reveals an open reading frame which encodes a protein of 103 amino acids. The genomic DNA encoding TRX was also isolated from S. pombe chromosomal DNA using PCR. The cloned sequence contains 1795 bp and encodes a protein of 103 amino acids. However, the C-terminal region obtained from the cDNA clone is -Val-Arg-Leu-Asn-Arg-Ser-Leu, whereas the C-terminal region deduced from the genomic DNA appears to contain -Ala-Ser-Ile-Lys-Ala-Asn-Leu. This indicates that S. pombe cells contain two kinds of TRX genes which have dissimilar amino acid sequences only at the C-terminal regions. The heterologous TRX 1C produced from the cDNA clone could be used as a subunit of T7 DNA polymerase, while the TRX 1G from the genomic DNA could not. The upstream sequence and the region encoding the N-terminal 18 amino acids of the genomic DNA were fused into the promoterless beta-galactosidase gene of the shuttle vector YEp357 to generate the fusion plasmid pYKT24. Synthesis of beta-galactosidase from the fusion plasmid was found to be enhanced by hydrogen peroxide, menadione and aluminum chloride. It indicates that the expression of the cloned TRX gene is induced by oxidative stress.

Aluminum Chloride↗

Influence of temperature and pH on the stability of dimethoxy biphenyl monocarboxylate HCl solutions.

The accelerated stability of dimethoxy biphenyl monocarboxylate x HCl (DDB-S) was investigated in 6 mg/mL water solution in the pH ranging 2-10 and the temperature of 45-85 degrees C. The observed rate of degradation followed first-order kinetics. The energy of activation for DDB-S degradation was calculated to be 14.1 and 16.5 Kcal/mole at pH 5 and in distilled water, respectively. The degradation rate constant (K(25 degrees C)) obtained by trending line analysis of Arrhenius plots for DDB-S was 5.3 x 10(-6) h(-1). The times to degrade 10% (t10) and 50% (t50) at 25 degrees C were 829 and 5,416 days, respectively. DDB-S exhibited the fastest degradation at pH 10 and the slowest rate at pH 5. In addition, at 65 degrees C, degradation rate constants of DDB-S were 0.066, 0.059, 5.460, 32.171, and 1.41 x 10(6) h(-1) at pH 2, 5, 8, 10 and in distilled water, respectively. These observations indicated that the rate-pH profile of DDB-S showed general acid-base catalysis reaction in the range of pH 2-10.

Biphenyl Compounds↗

Total occlusion of left main coronary artery by dilated main pulmonary artery in a patient with severe pulmonary hypertension.

A 34-year-old woman was admitted to the hospital because of recently aggravated right heart failure without angina for 5 months. When she was 25 years old, patch repair with Polytetrafluoroethylene (PTFE) was performed for the secondum type of atrial septal defect (ASD) with moderate pulmonary hypertension. The chest PA, echocardiography and cardiac catheterization at current admission revealed Eisenmenger syndrome without intracardiac shunt. Chest CT scan with contrast revealed markedly dilated pulmonary trunk, both pulmonary arteries and concave disfigurement of the left side of the ascending aorta suggesting extrinsic compression, as well as total occlusion of the ostium of the left main coronary artery that was retrogradly filled with collateral circulation from the right coronary artery. The coronary angiography showed normal right coronary artery and the collaterals that come out from the conus branch to the mid-left anterior descending artery (LAD) and that from distal right coronary artery to the left circumflex artery (LCX) and to the distal LAD, respectively. On aortography, the left main coronary artery was not visualized with no stump, suggestive of total occlusion of the ostium of the left main coronary artery. From our experience, it is possible to say that the occlusion of the ostium of the left main coronary can be induced by the dilated pulmonary artery trunk due to ASD with pulmonary hypertension and that, if the ASD closure was too late, the narrowing or obstruction of the left coronary artery could not be resolved even after operation owing to irreversible pulmonary hypertension.

Adult↗

Role of tumor necrosis factor-alpha in neuronal and glial apoptosis after spinal cord injury.

We investigated the role of tumor necrosis factor (TNF)-alpha in the onset of neuronal and glial apoptosis after traumatic spinal cord crush injury in rats. A few TUNEL-positive cells were first observed within and surrounding the lesion area 4 h after injury, with the largest number observed 24-48 h after injury. Double-labeling of cells using cell type-specific markers revealed that TUNEL-positive cells were either neurons or oligodendrocytes. One hour after injury, an intense immunoreactivity to TNF-alpha was observed in neurons and glial cells in the lesion area, but also seen in cells several mm from the lesion site rostrally and caudally. The level of nitric oxide (NO) also significantly increased in the spinal cord 4 h after injury. The injection of a neutralizing antibody against TNF-alpha into the lesion site several min after injury significantly reduced both the level of NO observed 4 h thereafter as well as the number of apoptotic cells observed 24 h after spinal cord trauma. An inhibitor of nitric oxide synthase (NOS), N(G)-monomethyl-l-arginine acetate (l-NMMA), also reduced the number of apoptotic cells. This reduction of apoptotic cells was associated with a decrease in DNA laddering on agarose gel electrophoresis. These results suggest that: (i) TNF-alpha may function as an external signal initiating apoptosis in neurons and oligodendrocytes after spinal cord injury; and (ii) TNF-alpha-initiated apoptosis may be mediated in part by NO as produced by a NOS expressed in response to TNF-alpha.

Animals↗

Antimutagenic activity of 5alpha-cholest-7-en-3beta-ol, a new component from the starfish asterina pectinifera.

From the butanol fraction of the starfish Asterina pectinifera Müler et Troschel (Asteriidae), we have isolated a new component, 5alpha-cholest-7-en-3beta-ol. Its antigenotoxic and antimutagenic activities were examined by the SOS chromotest with Escherichia coli PQ37 and by Ames test with Salmonella typhimurium TA1538, respectively. 5alpha-Cholest-7-en-3beta-ol showed potent antigenotoxic activity against the mutagens, both MNNG and NQO. For 100% of antigenotoxicity, the concentration of the compound applied against MNNG and NQO were 10 microg and 5 microg per reaction tube, respectively. Its antimutagenic activity with S. typhimurium TA1538 against the mutagen MNNG was very effective. When its concentrations were varied from 1 up to 10 microg dose per plate, the inhibition ratio of revertant CFU of TA1538 per plate was increased accordingly, from 25.2 to 99.2%. These results suggest that 5alpha-cholest-7-en-3beta-ol possesses antigenotoxic and antimutagenic activity and might be useful as a chemopreventive agent.

4-Nitroquinoline-1-oxide↗

Ginsenosides that produce differential antinociception in mice.

Ginsenoside Rc, Rd, and Re induced antinociception in writhing and formalin tests among five representative ginsenosides: Rb1, Rc, Rd, Re, and Rg1. However, these ginsenosides had no effect in the tail-flick test. The antinociceptive effects induced by three ginsenosides were dose dependent. ED50 was 20.5 (7.3-57.4 mg/kg) for Rc, 17 (11.0-27.6 mg/kg) for Rd, and 3.5 (1-12 mg/ kg) for Re in the writhing test and 62 (42-90 mg/kg) for Rc, 45 (20.5-99.0 mg/kg) for Rd, and 82 (48-139 mg/kg) for Re in the second phase of the formalin test. The antinociceptive effects were not blocked by the opioid receptor antagonist naloxone in the writhing and formalin tests. These three ginsenosides did not affect motor function. Ginsenoside Rc and Rd induced hypothermia for 30 to 60 min, and ginsenoside Rc induced hyperthemia after 150 min of treatment at doses of 100 mg/kg. These results suggest that ginsenosides such as Rc, Rd, or Re inhibit mainly chemogenic pain rather than thermal pain by the nonopioid system in mice.

Acetic Acid↗

Ginsenoside Rf, a trace component of ginseng root, produces antinociception in mice.

Ginseng root, a traditional oriental medicine, contains more than a dozen biologically active saponins called ginsenosides, including one present in only trace amounts called ginsenoside-Rf (Rf). Previously, we showed that Rf inhibits Ca2+ channels in mammalian sensory neurons through a mechanism requiring G-proteins, whereas a variety of other ginsenosides were relatively ineffective. Since inhibition of Ca2+ channels in sensory neurons contributes to antinociception by opioids, we tested for analgesic actions of Rf. We find dose-dependent antinociception by systemic administration of Rf in mice using two separate assays of tonic pain: in the acetic acid abdominal constriction test, the ED50 was 56+/-9 mg/kg, a concentration similar to those reported for aspirin and acetaminophen in the same assay; in the tonic phase of the biphasic formalin test, the ED50 was 129+/-32 mg/kg. Rf failed to affect nociception measured in three assays of acute pain: the acute phase of the formalin test, and the thermal (49 degrees C) tail-flick and increasing-temperature (3 degrees C/min) hot-plate tests. The simplest explanation is that Rf inhibits tonic pain without affecting acute pain, but other possibilities exist. Seeking a cellular explanation for the effect, we tested whether Rf suppresses Ca2+ channels on identified nociceptors. Inhibition was seen on large, but not small, nociceptors. This is inconsistent with a selective effect on tonic pain, so it seems unlikely that Ca2+ channel inhibition on primary sensory neurons can fully explain the behavioral antinociception we have demonstrated for Rf.

Abdominal Muscles↗

Ginsenosides induce differential antinociception and inhibit substance P induced-nociceptive response in mice.

Ginsenosides are main pharmacoactive molecules of ginseng. The antinociceptive activity of ginsenosides after intrathecal (i.t.) injection was examined in formalin test. We also investigated the effects of ginsenosides on substance P (SP) induced-pain behaviors by i.t. treatment using mice. Pretreatment of ginsenosides by i.t. induced the inhibition of biting and licking of hind paw injected with 1% formalin with dose-dependent manner. The ED50 was 23 (19-28, 95% C.I.) microg/mouse for acute phase and 15 (9-23, 95% C.I.) microg/mouse for tonic phase. Interestingly, cotreatment of ginsenosides with SP also inhibited SP-induced pain behaviors (scratching, licking or biting of hind portion of body) with dose-dependent manner. The ED50 for the inhibition of SP-induced pain behavior by ginsenosides was 30 (11-85, 95% C.I.) microg/mouse. These results suggest that ginsenosides have antinociceptive activity in formalin test and this effect is due to blocking of SP-induced nociceptive information to postsynaptic site(s) at the spinal level.

Analgesia↗

Further evidence of bradykinin involvement in septic shock: reduction of kinin production in vivo and improved survival in rats by use of polymer tailored SBTI with longer t1/2.

Involvement of bradykinin in septic shock and its therapeutic endeavor using soybean trypsin inhibitor (SBTI, Kunitz type) were investigated in an in vivo model of septic shock induced by pseudomonal elastase. Pseudomonal elastase injection at 0.5 mg/kg i.v. to guinea pigs resulted in elevation level of bradykinin in the blood from < 1 ng/ml to 25 ng/ml which was accompanied by a drop of mean arterial blood pressure (MABP) (about 45 mmHg). When native soybean trypsin inhibitor (SBTI, Kunitz type, 20 kDa) was injected, into this model, induction of bradykinin generation and hypotension by the bacterial protease treatment was completely obliterated as judged by the both levels of bradykinin and MABP. Specifically, by the treatment with SBTI, bradykinin levels did not increase and the drop of the blood pressure was minimal (< 10 mmHg) in this time frame (< 30 min). We designed and prepared succinylated gelatin-conjugated SBTI (suc-gel SBTI) with enlarged molecular mass (M(r) approximately 110,000) and higher area under the curve of the plasma concentration, which exhibits about 6 times longer plasma half-life (t1/2) and about 4 times larger area under the curve of plasma concentration. Suc-gel-SBTI suppressed the pseudomonal protease-induced shock much more effectively than native SBTI, the conjugate exhibited its effect for more than 3 h, while the native SBTI showed the effect only within 2 h after i.v. injection.

Animals↗

Isolation and characterization of Saccharomyces cerevisiae SAB2, a suppressor gene for temperature-sensitive phenotype of ARS-binding factor 1 mutant.

A high-copy number suppressor of yeast abf1-5 mutant, a temperature-sensitive lethal mutant, was isolated and named SAB2 (suppressor of ABF1). Hybridization to a yeast chromoblot and to prime clone grid filters revealed that the SAB2 gene was located near the yeast SUP3 on chromosome XV. The suppressor activity was contained in a 2.5 Kbp DNA region of the SAB2 plasmid. The nucleotide sequence of the DNA region contained a long open reading frame, which turned out to encode for yeast tryptophan permease. Four putative ABF1 binding sites were found in the promoter and the structural regions of the tryptophan permease gene. Binding of ABF1 to two of the sites tested in this study was detected. Our results indicate that ABF1 may be involved in the transcriptional control of the yeast tryptophan permease gene.

Amino Acid Transport Systems↗

Characterization of high affinity binding sites of non-steroidal anti-inflammatory drugs with respect to site-specific probes on human serum albumin.

A site-oriented study of nine non-steroidal anti-inflammatory drugs (NSAIDs), suprofen, ibuprofen, diclofenac sodium, pirprofen, flurbiprofen, ketoprofen, phenylbutazone, oxyphenbutazone, and ketophenylbutazone, on human serum albumin (HSA) was carried out at pH 7.4 by various direct and indirect methods to gain insight into the high affinity binding sites of NSAIDs. The binding was determined by equilibrium dialysis, circular dichroism and fluorescence methods in order to strengthen the results. Irrespective of the method used, close agreement between the binding parameters obtained by the different methods was obtained. A site-oriented description, as revealed by the fluorescent probe displacement method, suggests that site II and site I probes bound to HSA were selectively displaced by NSAIDs with a carboxyl group and without a carboxyl group, respectively. The absence of a carboxyl group of the NSAIDs changed the binding site from site II to site I. Different binding models describing the competitive and independent binding of a NSAID and a site-specific probe bound simultaneously to HSA further describe the respective high affinity binding sites for NSAIDs, thus underscoring the necessity of a carboxyl group in order for a NSAID to bind to site II. The presence of tyrosine, lysine and histidine amino acid residues in the binding of carboxyl group-containing NSAIDs to HSA was evident, whereas tryptophan is believed to take part in the binding of non-carboxyl group-containing NSAIDs. The present findings support the proposal that two separate primary binding sites exist for different NSAIDs; hence, an attempt to correlate the present results with those in literature has been made.

Anti-Inflammatory Agents, Non-Steroidal↗