Biomedical subjects
Publications and source records attributed to C Park.
An improved burying method for salvaging an amputated auricle is presented. We elevated a mastoid skin flap and a fascial flap simultaneously and inserted the denuded auricular cartilage between them. This procedure can maintain the auricular cartilage in a more natural form by eliminating undue skin tension and can give a favorable aesthetic result.
During the search for unknown factors involved in motility, we have found that expression of the flagellar master operon flhDC is affected by mutations of the pta and ackA genes, encoding phosphotransacetylase and acetate kinase, respectively (S. Shin, J. Sheen, and C. Park, Korean J. Microbiol. 31:504-511, 1993). Here we describe results showing that this effect is modulated by externally added acetate, except when both pta and ackA are mutated, suggesting the role of acetyl phosphate, an intermediate of acetate metabolism, as a regulatory effector. Furthermore, the following evidence indicates that the phosphorylation of OmpR, a trans factor for osmoregulation, regulates flagellar expression. First, in a strain lacking ompR, the expression of flhDC is no longer responsive to a change in the level of acetyl phosphate. Second, an increase in medium osmolarity does not decrease flhDC expression in an ompR mutant. It is known that such an increase normally enhances OmpR phosphorylation. Third, OmpR protein binds to the DNA fragment containing the flhDC promoter, and its affinity is increased with phosphorylation by acetyl phosphate. DNase I footprinting revealed the regions of the flhDC promoter protected by OmpR in the presence or absence of phosphorylation. Therefore, we propose that the phosphorylated OmpR, generated by either osmolarity change or the internal level of acetyl phosphate, negatively regulates the expression of flagella.
To determine whether alterations in the mechanical properties and calcium transients of myocytes are important factors in the evolution of the postinfarcted heart, these physiological parameters were measured in the viable muscle cells of the left ventricle 6 h, 2-3 days, 1 wk, and 1 mo after coronary artery occlusion and the documentation of left ventricular failure. In addition, the effects of propionyl-L-carnitine (PLC) on shortening properties and calcium dynamics of single myocytes were established to demonstrate whether the potential increase in ATP generation by this intervention improved myocyte cell function. Myocardial infarction was associated with a progressive increase in length of the spared myocytes, whereas the changes in myocyte diameter were apparent only at the 1-mo interval. Mechanically, myocyte shortening was decreased 43% at 6 h, 34% at 2-3 days, 26% at 1 wk, and 41% at 1 mo after infarction. Similar abnormalities were noted in the velocity of myocyte shortening. Peak systolic calcium was decreased at all intervals after infarction. In contrast, diastolic calcium remained within control values. PLC was capable of ameliorating the mechanical behavior and calcium transients of myocytes, particularly 1 mo after infarction. Thus alterations in muscle cell performance may be important determinants in the development and progression of ischemic cardiomyopathy, and interventions improving myocyte contractility may interfere with the unfavorable outcome of the disease.
To identify the clinicopathological events including nm23 expression that underlies progression in renal cell carcinoma, a retrospective analysis of patients with renal cell carcinoma was performed. Ninety-eight cases of radical nephrectomies with extensive regional or para-aortic lymph node dissection were assessed for clinicopathological variables, and eighty-five cases underwent nm23/NDPK-A protein immunohistochemical staining. Significant parameters in survival were tumor size, histologic pattern, Fuhrman's nuclear grade, pathologic T(pT) stage, pathologic N stage, M stage, tumor thrombi, location of metastasis, and nm23 staining intensity. To assess the relationship with survival, the tumors with low and high nm23 expressions were compared. The fifty-nine patients with a high staining intensity had a significantly worse survival than did the twenty-six with a low staining intensity (p = 0.0015). Additionally nm23 staining intensity was correlated with tumor size, Fuhrman's nuclear grade, pT, and distant metastasis. Therefore, the immunostaining intensity of nm23 protein could be used as a prognostic parameter with an inverse correlation.
A case of xanthoma of the liver in a 61-year-old Korean woman with multiple myeloma, hyperlipidemia and xanthoma of the skin is described. Microscopically, the liver showed a multiple xanthomatous collection of foamy histiocytes as well as diffuse sinusoidal infiltration of the foam cells. This hepatic accumulation of foam cells seems to be related to hyperlipidemia of the patient. The mechanism of hyperlipidemia in multiple myeloma is discussed.
Coxiella burnetii is a well-known causative agent of granulomatous inflammation and an inducer of morphological changes and transformation of human B lymphocytes in vitro. An association of the organism with polymorphic reticulosis (PMR), a malignant granulomatous inflammation characterized by polymorphic lymphocytes, was examined. The infection of C. burnetii was demonstrated in all cases tested, especially in polymorphic lymphocytes. Also the presence of morphologically transformed peripheral blood lymphocytes (PBLs) infected with C. burnetii was demonstrated. In cultures of blood lymphocytes, C. burnetii-infected polymorphic cells identified as B cells became immortalized in vitro. These findings implicate the role of C. burnetii in the process of PMR.
Ribose-binding protein (RBP) consists of two alpha/beta globular units; the N domain being composed of four helices (I, II, III and IX) and six sheets (A, B, C, D, E and K), and the C domain with five helices (IV, V, VI, VII and VIII) and six sheets (F, G, H, I, J and L). The two domains are connected by three strands. In the previous study, tyrosine residues in the RBP were substituted by phenylalanine to examine the fluorescence property of each chromophore. Since the three tyrosine residues are scattered in the two domains of RBP, residues 32 and 261 in the N domain and 115 in the C domain, we were able to monitor the state of protein folding using unaltered tyrosine as a local probe. The final structures of the mutant proteins show little differences from those of wild-type as judged by circular dichroism spectra. The equilibrium and kinetic folding behaviors of the mutant RBPs were examined by fluorescence spectroscopy. The equilibrium data obtained from the mutant RBPs conform to the two-state transition involving the native and unfolded species. However, kinetic studies indicate that there exists an intermediate formed transiently during the folding or unfolding process, which was not detected in equilibrium experiments. In unfolding kinetics of the mutant protein retaining only the N domain tyrosine residues, a striking change in fluorescence was observed as an initial jump, suggesting the presence of a partial unfolding step of RBP around the Tyr32 chromophore, since the fluorescence of Tyr261 does not change upon folding. This occurred immediately after mixing with 0.6 to 1 M range of guanidine hydrochloride and was completed in less than three seconds of the mixing dead time. The partial increase of fluorescence appears to be due to the dissociation of a quenching group, the carboxyl side-chain of Asp249 located on helix IX, from the Tyr32 fluorophore. The successive unfolding process reflects a process of release from the second quenching group at Asp2 on the sheet A. The substitution at Tyr261 on sheet K by phenylalanine reveals an additional kinetic phase in refolding, in which the folding from unfolded into an intermediate form seems similar to wild-type in time scale, whereas the next step leading to the formation of native protein becomes slower.(ABSTRACT TRUNCATED AT 400 WORDS)
The objective of this study was to determine whether more than one DQB gene is expressed in three BoLA haplotypes that have a duplicated DQ region. Leukocyte mRNA from three animals genotyped at the BoLA-A, DQB, and DRB3 loci was used as template for reverse transcription-polymerase chain reaction (RT-PCR), cloning, and DNA sequencing. Five DQB alleles were identified. All cDNA clones were 564 base pairs (bp) in length, including 507 bp of nonprimer-derived sequence that contained the coding sequence for the full length of exon 2 and 74 amino acids of exon 3. Three alleles were assigned to the DQB1 locus and two were assigned to DQB2 on the basis of sequence comparisons with previously reported alleles. The expression of DQB1 and DQB2 in individual animals was examined by RT-PCR followed by double digestion of the 564 bp PCR products with Eco O109 I and Dra III in order to discriminate the DQB alleles. Evidence that DQB1 and DQB2 are both transcribed was obtained for three different BoLA haplotypes with DQB duplications, DQB10, DQB11C, and DQB12. These results suggest that the duplication or deletion event that gave rise to the DQB1 and DQB2 genes is a relatively recent event in the evolution of the cattle MHC.
We studied the vascular anatomy of the perioral region by dissecting fresh cadavers. The anatomy of perioral branches of the facial artery consistently confirmed the existence of a septal branch and an alar branch to the upper lip and a vertical labiomental branch to the lower lip. New regional flaps supplied by these perioral arterial branches are proposed in this paper. The mucosal flap from the upper lip supplied by the deep septal branch or the alar branch of facial artery can be used to restore lower lip defects. A composite flap from the lower lip supplied by the vertical labiomental branch of the facial artery can be used safely to restore combined defects of the upper lip and nose or partial defects of the lower lip.
Chemoreceptor Trg and osmosensor EnvZ of Escherichia coli share a common transmembrane organization but have essentially unrelated primary structures. We created a hybrid gene coding for a protein in which Trg contributed its periplasmic and transmembrane domains as well as a short cytoplasmic segment and EnvZ contributed its cytoplasmic kinase/phosphatase domain. Trz1 transduced recognition of sugar-occupied, ribose-binding protein by its periplasmic domain into activation of its cytoplasmic kinase/phosphatase domain as assessed in vivo by using an ompC-lacZ fusion gene. Functional coupling of sugar-binding protein recognition to kinase/phosphatase activity indicates shared features of intramolecular signalling in the two parent proteins. In combination with previous documentation of transduction of aspartate recognition by an analogous fusion protein created from chemoreceptor Tar and EnvZ, the data indicate a common mechanism of transmembrane signal transduction by chemoreceptors and EnvZ. Signalling through the fusion proteins implies functional interaction between heterologous domains, but the minimal sequence identity among relevant segments of EnvZ, Tar, and Trg indicates that the link does not require extensive, specific interactions among side chains. The few positions of identity in those three sequences cluster in transmembrane segment 1 and the short chemoreceptor sequence in the cytoplasmic part of the hybrid proteins. These regions may be particularly important in physical and functional coupling. The specific cellular conditions necessary to observe ligand-dependent activation of Trz1 can be understood in the context of the importance of phosphatase control in EnvZ signalling and limitations on maximal receptor occupancy in binding protein-mediated recognition.
We isolated and characterized mutants defective in nuo, encoding NADH dehydrogenase I, the multisubunit complex homologous to eucaryotic mitochondrial complex I. By Southern hybridization and/or sequence analysis, we characterized three distinct mutations: a polar insertion designated nuoG::Tn10-1, a nonpolar insertion designated nuoF::Km-1, and a large deletion designated delta(nuoFGHIJKL)-1. Cells carrying any of these three mutations exhibited identical phenotypes. Each mutant exhibited reduced NADH oxidase activity, grew poorly on minimal salts medium containing acetate as the sole carbon source, and failed to produce the inner, L-aspartate chemotactic band on tryptone swarm plates. During exponential growth in tryptone broth, nuo mutants grew as rapidly as wild-type cells and excreted similar amounts of acetate into the medium. As they began the transition to stationary phase, in contrast to wild-type cells, the mutant cells abruptly slowed their growth and continued to excrete acetate. The growth defect was entirely suppressed by L-serine or D-pyruvate, partially suppressed by alpha-ketoglutarate or acetate, and not suppressed by L-aspartate or L-glutamate. We extended these studies, analyzing the sequential consumption of amino acids by both wild-type and nuo mutant cells growing in tryptone broth. During the lag and exponential phases, both wild-type and mutant cells consumed, in order, L-serine and L-aspartate. As they began the transition to stationary phase, both cell types consumed L-tryptophan. Whereas wild-type cells then consumed L-glutamate, glycine, L-threonine, and L-alanine, mutant cells utilized these amino acids poorly. We propose that cells defective for NADH dehydrogenase I exhibit all these phenotypes, because large NADH/NAD+ ratios inhibit certain tricarboxylic acid cycle enzymes, e.g., citrate synthase and malate dehydrogenase.
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During meiotic prophase in male mammals, the sex chromosomes are transcriptionally inactivated and form a condensed chromatin domain known as the sex body. It is not known how the assumption of this chromatin configuration is determined and regulated. We used various genetic models to test whether a complete sex-chromosome pair, effective sex-chromosome pairing, or an intact X chromosome is required for sex-body formation or transcription inactivation. The sex chromosome aberrations studied did not interfere with sex-body formation, and there is no evidence for inactivation failure or reactivation of the aberrant sex chromosomes. The results of this study suggest that control of sex-body formation is not intrinsic to the sex chromosomes and thus may be at the level of the testis.
The immune response is impaired in patients with malignancy, and radiation therapy (RT) can exacerbate the cancer induced-attenuation of immune response. In order to search for the fine mechanisms behind the RT-induced attenuation of cell-mediated immune response, we measured the number of lymphocytes in peripheral blood, its subsets, and lymphoblast transformation induced by phytohemagglutinin (PHA), purified protein derivatives (PPD), mitogenic monoclonal antibody anti-CD3, and mitogenic combination of anti-CD2 antibodies 9-1 and 9.6 before and after RT in 19 patients with squamous cell lung cancer. Radiation therapy significantly decreased the total numbers of lymphocytes, CD-3, CD-4, and CD8-positive lymphocytes in peripheral blood. However, RT did not change the percentages of lymphocytes and its subsets. Radiation therapy increased the percentage of interleukin 2 (IL-2) receptor-positive lymphocytes, and RT significantly decreased in vitro lymphoblast transformation by PHA, PPD, or monoclonal antibodies to T-cell surface antigens (anti-CD2 or anti-CD3). In vitro incubation with IL-2 did not increase lymphoblast transformation by anti-CD3 before RT but significantly increased after RT. In conclusion, we suggest that one of the fine mechanisms behind the RT-induced suppression of immune responsiveness of patients with lung cancer is a defect in IL-2 synthesis by lymphocytes.
Flow cytometric DNA analysis was performed on 17 rhabdomyosarcomas in conjunction with a histopathological review to determine the usefulness of this technique to predict the biologic behavior of the tumor and to establish the characteristic ploidy pattern of rhabdomyosarcoma compared to other small round cell tumors occurring in childhood. Aneuploidy including near-tetraploidy is the most common ploidy pattern encountered, followed by multiploidy and diploidy, and the presence of multiploidy in this tumor is useful for differentiating rhabdomyosarcoma from other kinds of small round cell tumors in which there are rare previous reports on occurrence of multiploidy. Even though there is no significant correlation between ploidy pattern and histologic type of rhabdomyosarcoma, patients with multiploid tumors or aneuploid tumors with a DNA index of 1.10-1.80 tend to have a high risk of treatment failure. Therefore, the ploidy pattern seems to be useful for predicting the patient's survival in concert with other variables.
Both dimethyl methylphosphonate (DMMP) and trimethylphosphate (TMP) are organophosphorous compounds that can evoke sterility in male rodents. The following studies examined the pathology of reproductive organ, especially on the testis, by light microscopy after treatment with both agents. Adult male rats were treated per oral with DMMP, 1,750 mg/Kg, for up to 12 weeks and per oral with TMP, 400 mg/Kg for up to 5 weeks. After 5 weeks of treatment with DMMP there were occasional multinucleated giant cells composed of late spermatids in stages X, XI, XII as well as cytoplasmic vacuolation of Sertoli cell. Anachronistic spermiations were seldom, if ever, seen throughout the experiment. After 7 weeks of DMMP those were markedly diminished. The overall changes after treatment with TMP are somewhat similar to those treated with DMMP. The major changes were composed of aggregate of multinucleated giant cells and maturation arrest at spermatid level, which appear immediately after administration of TMP. The peak frequency in the emergence of multinucleated giant cells in treatment with TMP was noted just a week after treatment, but afterwards declined. Maturation arrest was prominent after 3 weeks in the cases treated with TMP.
Immunohistochemical study and flow cytometric DNA analysis were done on seven cases of clear cell sarcoma of the kidney (CCSK) to speculate its histogenesis and to access the diagnostic usefulness of these methods in the differential diagnosis of Wilm's tumor. Clinically, CCSK is a rare malignant renal tumor of children with a propensity to metastasize to bone. Arborizing vascular pattern surrounding the tumor cells which have clear cytoplasm is characteristic histologic finding. Immunohistochemically, only vimentin was diffusely demonstrated in the tumor cell membrane and cytoplasm. In flow cytometric DNA analysis, four cases showed diploidy and two cases near diploidy. CCSK is a separate disease entity with characteristic clinicopathologic, immunohistochemical and flow cytometric findings in distinction from Wilms' tumor. Considering the histologic and immunohistochemical findings, the possible histogenetic mechanism of CCSK seems to be in common with congenital mesoblastic nephroma (CMN), that is primitive mesenchymal cells which committed early stromagenic activity.
Iron is essential for the growth of all living cells. One of the most important intracellular roles of iron is the activation of ribonucleotide reductase, which is indispensible to the production of deoxyribonucleotide necessary for DNA synthesis. Deferoxamine (DFO) is an iron chelating agent and has been known to have an antiproliferative effect in various malignant cells including hepatocellular carcinoma and the effect seems to be related to depletion of iron. This study was undertaken to investigate the effect of DFO on preneoplastic lesions in chemically induced hepatocarcinogenesis. The resistant hepatocyte model was used and Sprague Dawley rats were divided into the following groups; I: normal control, II: carcinogen administered group, III: carcinogen and DFO administered group. Rats were sacrificed at 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks and 8 weeks after partial hepatectomy (PH). DFO (50 mg/kg/day, I.P.) was daily injected from 3 weeks before administration of carcinogen to the time when rats were sacrificed. Hepatic iron content was higher in group II than in group III, especially at 3 days and 1 week after PH. Hyperplastic lesions of resistant hepatocytes were less well developed in group III than in group II. Bromodeoxyuridine labelling indices of oval cells and hyperplastic lesions of resistant hepatocytes were higher in group II than in group III except for rats examined at 3 days after PH. The results suggest that DFO has an antiproliferative effect on preneoplastic lesions in hepatocarcinogenesis and it might be related to reduction of the hepatic iron.