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Biomedical subjects

I Park

Publications and source records attributed to I Park.

At least 19 recordsLinked to original sources

Origins of the first HLA specificities.

Following the discovery of the first histocompatibility antigen "MAC" in 1958, numerous independent laboratories began identifying HLA specificities with allo-antibodies. During the span of about a decade, 1958-1970, virtually all of the common HLA-A and HLA-B antigens were identified by various names and presented at the International Histocompatibility Workshops by means of different serological methods. Because many of the independently discovered specificities were found to be reactive to similar determinants on lymphocytes, it became necessary to classify the antigens by means of a standard method. The micro lymphocytotoxicity test was chosen to be the basis for future antigen testing, thereby allowing the various laboratories to confidently exchange sera. At the 1968 WHO Nomenclature meeting, the naming of the first antigen ultimately gave rise to the designation "HLA" in the human MHC Class I antigen system. This paper looks back upon the origins of the early serologically identified HLA specificities and their respective founders.

HLA-A Antigens↗

Translational suppression by hammerhead ribozymes and inactive variants in S. cerevisiae.

The activity of hammerhead ribozymes in S. cerevisiae was assessed using two ribozymes that were designed to intramolecularly attack the hepatitis B viral X mRNA. The ribozymes effectively suppressed the expression of the X-lacZ fusion gene, when they were inserted at the 5' end of the X mRNA. The ribozymes cleaved the target RNA efficiently at the targeted phosphodiester bond, but the inactive mutants carrying G5-to-A substitution in the core did not, as the total RNA preparations of yeast extracts was assayed by primer extension. These G5A mutants, however, exerted the suppression as effectively as the wild-type ribozymes. The results, with several mutations introduced to a ribozyme, suggested that either mere formation of hammerhead-like structures with the three stems, or the formation of any two stems, could inhibit translation. Thus, the hammerhead-like structures, leading to cleavage or not, could effectively suppress translation, especially when formed around the initiation codon. The G5-to-A and U7-to-G mutations and replacement of the stem-II hairpin tetraloop did not appear to affect the formation of the inhibitory structure(s). The inhibition that was observed when stems I and III were directly connected without a loop or with a stem II hairpin was completely relieved when they were connected with only the loop of stem II (not containing the stem portion).

DNA Primers↗

Tumor suppressor p53 is required to modulate BRCA1 expression.

Individuals carrying mutations in BRCA1 or p53 genes are predisposed to a variety of cancers, and both tumor suppressor genes have been implicated in DNA damage response pathways. We have analyzed a possible functional link between p53 and BRCA1 genes. Here we show that BRCA1 expression levels are down-regulated in response to p53 induction in cells that undergo either growth arrest, senescence, or apoptosis. Physiological stimuli, such as exposure to DNA-damaging agents, also result in negative regulation of BRCA1 levels in a p53-dependent manner prior to causing cell cycle arrest. Nuclear run-on experiments and luciferase reporter assays demonstrate that the changes in BRCA1 expression are mainly due to transcriptional repression induced by p53. In conclusion, the data show that BRCA1 expression levels are controlled by the presence and activity of wild-type p53 and suggest the existence of an intracellular p53/BRCA1 pathway in the response of cells to stress conditions.

Animals↗

Five cases of ocular toxocariasis confirmed by serology.

We report 5 cases of ocular toxocariasis in Korean adults complaining of visual impairment along with floating or bubbling sensation. Fundoscopic examination revealed a retinal detachment along with exudate in 4 cases. They all showed typical reaction by ELISA and immunoblot against Toxocra excretory-secretory antigen. One case showed high level of anti-Toxocara IgE antibodies (34,000 Toxocara units/L) as well as increased level of serum total IgE antibodies and the specific IgE antibodies for 3 inhalant antigens, suggesting that high level of anti-Toxocara IgE antibodies was associated with an atopic status. Clinical manifestations were improved after the sequential use of steroids then mebendazole. We also suggest that ocular toxocariasis should be thoroughly investigated even when an evocative uniocular inflammatory lesion is encountered in peripheral retina without a systematic disease.

Adult↗

Repression of hepatitis B virus X gene expression by hammerhead ribozymes.

The X protein (HBx) of human hepatitis B virus (HBV) is a transcriptional activator protein. The HBx protein plays an important role in viral replication in HBV infected cells and the liver diseases including hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Therefore, the repression of HBx gene expression by hammerhead ribozymes may be a good way to inhibit HBV replication and cure HBV-related liver diseases. We designed two hammerhead ribozymes, RzA and RzB, to cleave target sites at nucleotides 114 and 309 in the HBx open reading frame (ORF), respectively. In vitro, RzA and RzB cleaved HBx RNAs at their target sites up to 52 and 75%, respectively; however, the disabled ribozymes (dRzs) which have mutations in the catalytic site did not cleave the target RNAs at all. When each of the ribozymes were cotransfected into HepG2 cells with HBx expression plasmid, RzA and RzB reduced the level of HBx mRNA to 40 and 57%, respectively. The transactivation activity of HBx protein was also reduced dramatically by the ribozymes. These results suggest that the hammerhead ribozymes, RzA and RzB, can be used for the gene therapy of liver diseases caused by HBV.

Catalytic Domain↗

Identification of the Tapasin gene in the chicken major histocompatibility complex.

The Tapasin molecule plays a role in the assembly of major histocompatibility complex (Mhc) class I molecules in the endoplasmic reticulum, by mediating the interaction of class I-beta2-microglobulin dimers with TAP. We report here the identification of the Tapasin gene in the chicken Mhc (B complex). This gene is located at the centromeric end of the complex, between the class II B-LBI and B-LBII genes. Like its human counterpart it comprises 8 exons, but features a significantly reduced intron size as compared to the human gene. Chicken Tapasin codes for a transmembrane protein with a probable endoplasmic reticulum retention signal. Exons IV and V, and possibly exon III, code for separate domains that are related to the immunoglobulin (Ig) superfamily (this relationship was so far unrecognized for human Tapasin domain IV which has lost its two cysteines). Two different cDNAs corresponding to the Tapasin gene were isolated, possibly related to alternative splicing events; the Ig-like domain encoded by exon IV is missing in one of the cDNAs, suggesting either that this domain is not necessary for the protein to perform its function, or that the two alternatively spliced cDNAs are translated into two functionally different forms of the protein.

Amino Acid Sequence↗

Nonvitrectomizing vitreous surgery: a strategy to prevent postoperative nuclear sclerosis.

OBJECTIVE: The development or progression of postoperative nuclear sclerosis is the most common complication of successful vitrectomy in elderly patients. The authors treated idiopathic epimacular proliferation (EMP) with nonvitrectomizing vitreous surgery in an attempt to prevent postoperative nuclear sclerosis. DESIGN: Prospective, nonrandomized, comparative case series. PARTICIPANTS: The authors surgically removed membranes from the sensory retina in 21 eyes of 21 patients with EMP. INTERVENTION: Neither intravitreal infusion nor vitrectomy of any kind was performed during the procedure. The peeled membrane was left floating in the vitreous cavity in 11 (group 1) eyes and removed in 10 eyes (group 2). Nonoperated fellow eyes served as controls. MAIN OUTCOME MEASURES: Visual acuity, slit-lamp and/or Scheimpflug photography, and refractometry were performed pre- and postoperatively to evaluate changes in the degree of lenticular opacity. RESULTS: There was no difference in the rate of development or progression of nuclear sclerosis or the degree of myopic shift between operated and control eyes during the postoperative follow-up period (mean, 9.7 months). No serious complications were noted. There was no difference in postoperative course between patients in the two operative groups. CONCLUSIONS: Although interpretation of the results of this study is limited due to its small size and short follow-up, nonvitrectomizing vitreous surgery seems to decrease the postoperative development or progression of nuclear sclerosis in patients with idiopathic EMP.

Aged↗

Unguarded mitral orifice, mirror-imaged atrial arrangement, and discordant atrioventricular connections.

We report two autopsy proven cases of unguarded mitral orifice associated with mirror-imaged atrial arrangement, discordant atrioventricular connections, double outlet right ventricle, pulmonary valvar stenosis or atresia, and atrialisation of the morphologically left ventricle. The morphologically left atrioventricular junction was devoid of valvar leaflets, and there was no tension apparatus within the ventricle. To the best of our knowledge, this is the first description of this rare cardiac malformation.

Abnormalities, Multiple↗

A case of presumed ocular toxocariasis in a 28-year old woman.

This is a case of presumed ocular toxocariasis in a 28-year old woman complaining of a sudden onset of nasal side field defect of the right eye. The patient had been suffering from uveitis for ten months. Fundoscopic examination of the right eye showed a rhegmatogenous retinal detachment. Furthermore, a retinochoroidal granulomatous lesion was observed nearby the tear site. Scleral buckling, cryotherapy, and gas injection(SF6, pure gas, 0.7 cc) were conducted. Mebendazole was prescribed for one month at 25 mg/kg per body weight daily. Even though the interventions resulted in the recovery of the field defect, anti-Toxocara IgG and IgE titer levels did not decrease when checked three months after the treatment ended. This is the first confirmed serological ocular toxocariasis case in Korea. Uveitis may be a clinical presentation prior to retinal detachment of a person with toxocariasis.

Adult↗

Study of mandibular movements in mandibulectomy patients--border movements and functional movements during mastication, deglutition and speech.

In mandibulectomy patients who have not undergone surgical reconstruction, the remaining mandibular segment is unstable and often deviated. Its movements have low reproducibility during mastication, deglutition and speech. The purpose of this study was to clarify three-dimensionally the differences in mandibular movements for each of these oral functions in mandibulectomy patients with and without mandibular continuity. Four mandibulectomy subjects (Group I) without mandibular continuity and three subjects (Group II) with mandibular continuity were selected. Their mandibular movements were recorded using a jaw movement tracking device with six degrees of freedom. Each movement was assessed graphically at the virtual incisor point and the rotational angles of the mandible in the frontal, sagittal and horizontal plane were analyzed. The findings were as follows; 1. In Group I, the border movements at the virtual incisor point exhibited an irregular and asymmetric envelope deviated to the resected side in the frontal plane, whereas Group II exhibited a smooth and symmetric envelope. 2. In Group I, the rotational angles in the frontal plane during border movements and mastication, in all planes during speech, and in the frontal and horizontal plane during deglutition were significantly larger than in Group II. A comparison among border and all functional movements in mandibulectomy patients revealed characteristic movements in the rotation of the mandible in the frontal plane. It is suggested that the rotational angle of the mandible is a useful parameter for assessment of mandibular movements in mandibulectomy patients.

Aged↗

Size characterization of liposomes by flow field-flow fractionation and photon correlation spectroscopy. Effect of ionic strength and pH of carrier solutions.

The effect of ionic strength and pH of carrier solutions on the separation of liposomes by flow field-flow fractionation (flow FFF) has been studied for the determination of accurate vesicle size distribution of liposomes. Retention behaviors of liposomes (PC/PG/cholesterol) are observed in typical buffer solutions (PBS and Tris-HCl) of various ionic strengths as carrier liquids in flow FFF. The average diameters of collected fractions at each flow FFF run are measured by photon correlation spectroscopy (PCS) for the comparison with FFF calculations at corresponding time interval of collected fractions. A reasonable separation of liposomes is observed at I = 0.016 M for both buffer solutions. Retention of liposomes is found to be elongated at ionic strengths higher than an optimum condition found experimentally, but it is shortened at a lower ionic strength due to the electrostatic interaction between the channel wall and the liposomes. Finally, size distributions of liposomes are provided comparing the liposome preparations by flow FFF.

Drug Carriers↗

Glycopeptide antibiotic resistance genes in glycopeptide-producing organisms.

The mechanism of high-level resistance to vancomycin in enterococci consists of the synthesis of peptidoglycan terminating in D-alanyl-D-lactate instead of the usual D-alanyl-D-alanine. This alternate cell wall biosynthesis pathway is ensured by the collective actions of three enzymes: VanH, VanA, and VanX. The origin of this resistance mechanism is unknown. We have cloned three genes encoding homologs of VanH, VanA, and VanX from two organisms which produce glycopeptide antibiotics: the A47934 producer Streptomyces toyocaensis NRRL 15009 and the vancomycin producer Amycolatopsis orientalis C329.2. The predicted amino acid sequences are highly similar to those found in VRE: 54 to 61% identity for VanH, 59 to 63% identity for VanA, and 61 to 64% identity for VanX. Furthermore, the orientations of the genes, vanH, vanA, and vanX, are identical to the orientations found in vancomycin-resistant enterococci. Southern analysis of total DNA from other glycopeptide-producing organisms, A. orientalis 18098 (chloro-eremomycin producer), A. orientalis subsp. lurida (ristocetin producer), and Amycolatopsis coloradensis subsp. labeda (teicoplanin and avoparcin producer), with a probe derived from the vanH, vanA, and vanX cluster from A. orientalis C329.2 revealed cross-hybridizing DNA in all strains. In addition, the vanH, vanA, vanX cluster was amplified from all glycopeptide-producing organisms by PCR with degenerate primers complementary to conserved regions in VanH and VanX. Thus, this gene sequence is common to all glycopeptide producers tested. These results suggest that glycopeptide-producing organisms may have been the source of resistance genes in vancomycin-resistant enterococci.

Actinobacteria↗

[Catheter intervention for adult congenital heart diseases].

The efficacy of catheter intervention for adult congenital heart diseases was evaluated in 27 patients aged 20 to 52 years (mean age at catheterization 25 +/- 7 years) from 1986 to 1996. Four patients had pulmonary valve stenosis, four had aortic valve stenosis, three had coarctation of the aorta, 10 had pulmonary artery stenosis, four had cyanotic heart diseases and aorto-pulmonary collateral arteries, one had patent ductus arteriosus, and one had cyanotic heart disease and stenotic Blalock-Taussig shunt. Balloon dilation was successful in all patients with pulmonary valve stenosis, and follow-up evaluation (1-8 years) showed no restenosis in any patients. Balloon dilation was successful in all patients with aortic valve stenosis, and follow-up evaluation (0.5-5 years) showed transvalvular pressure gradient < 50 mmHg. Stenosis was relieved successfully in all patients with coarctation of the aorta, and follow-up evaluation showed no restenosis. Balloon dilation was successful in eight of 13 locations (62%) in patients with pulmonary artery stenosis. Coil embolization was successful in all patients with cyanotic heart diseases and aortopulmonary collateral arteries. In a patient with patent ductus arteriosus, two coils were placed in the ductus arteriosus but were retrieved because hemolysis was observed after the embolization. These data indicate that catheter intervention in young adults with congenital heart diseases is as effective as in children.

Adult↗

Diamond-dusted silicone cannula for epiretinal membrane separation during vitreous surgery.

PURPOSE: To report a diamond-dusted silicone cannula as a tool for membrane separation during vitreous surgery. METHODS: A diamond-dusted silicone cannula was fashioned from flexible silicone tubing with a beveled tip and coated with diamond fragments for use during vitreous surgery. RESULTS: The instrument was used successfully in seven eyes with idiopathic macular hole and was found to be particularly useful for removing residual vitreous cortex and epiretinal membranes from around the hole. It was also effective in removing "immature membranes" in three eyes with proliferative vitreoretinopathy. CONCLUSION: The diamond-dusted silicone cannula is a useful tool for removing thin epiretinal membranes and vitreous cortex that may be difficult or nearly impossible to remove safely using other techniques.

Catheterization↗

Prognostic markers of intravesical bacillus Calmette-Guérin therapy for multiple, high-grade, stage T1 bladder cancers.

BACKGROUND: Prediction of a response to intravesical bacillus Calmette-Guérin (BCG) therapy for bladder cancer is clinically important. We determined whether several molecular markers have prognostic value in intravesical BCG therapy for multiple, high-grade, stage T1 bladder cancers. METHODS: The expressions of p53 (clone D07), bcl-2 (100-D5), cathepsin-D (C5), c-myc(9E11), c-erbB-2 (CB11) and Ki-67 (MM1) were determined by immunohistochemistry in paraffin-embedded tissues from 32 multiple, T1, grade II-III bladder cancer patients (15 BCG responders, 17 nonresponders) who had undergone a single course of BCG therapy (Pasteur strain, 5 x 10(8) CFU weekly for 6 weeks) after complete removal of the tumors. The association between the expression of these markers and the response to BCG was assessed by univariate and multivariate analyses. RESULTS: There was no difference in patient and tumor characteristics between the 2 groups. Using multivariate analysis, the only useful marker was p53, with the overexpression of the p53 protein inversely related to the response to BCG therapy (P = 0.0182). CONCLUSION: Our results suggest that the status of p53 expression offers significant clinical information and may be a useful tool in the selection of suitable candidates for BCG therapy in multiple, high-grade stage T1 bladder cancer patients.

Adjuvants, Immunologic↗

Deoxycytidine kinase and deoxyguanosine kinase of Lactobacillus acidophilus R-26 are colinear products of a single gene.

Three of the four deoxynucleoside kinases required for growth of Lactobacillus acidophilus R-26 exist as heterodimeric pairs specific for deoxyadenosine (dAK) and deoxycytidine (dCK) or dAK and deoxyguanosine (dGK). However, only two tandem genes, dak/dgk, are found, and are expressed only as dAK/dGK in transformed Escherichia coli. Sequencing peptides spanning 63% of the native dCK subunit revealed a sequence identical to that deduced from dgk (beginning MTVIVL...), except that dCK lacks residues 2 and 3 (dCK is M..IVL; dGK is .TVIVL). Also, mass spectrometry indicates that native dCK and dGK subunits are identical in mass adjusted for the first three residues. Furthermore, the native enzymes have identical isoelectric pH values, indicating an equal number of charged residues. To enable E. coli to express peptide having the native dCK sequence, codons 2 and 3 were deleted from the dgk portion of the tandem genes, resulting in expression of protein having the specificities and regulatory properties of native dAK/dCK, including heterotropic stimulation of dAK activity by deoxycytidine or dCTP (not deoxyguanosine or dGTP) and end-product inhibition of the respective activities by dATP and dCTP. Subcloning normal and mutant dgk yielded homodimeric dGK and dCK, respectively. The dCK homodimer strongly resembles human dCK, with a low K(m) for deoxycytidine, the ability to phosphorylate deoxyadenosine and deoxyguanosine at much higher K(m) values, and end-product inhibition by dCTP. Thus two distinct and specific enzymes evidently are derived from a single Lactobacillus gene. The mechanism by which this occurs in vivo has yet to be elucidated.

Amino Acid Sequence↗