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Biomedical subjects

H J Kwon

Publications and source records attributed to H J Kwon.

At least 73 records · Page 4Linked to original sources
PubMed1996

Ovarian serous cystadenoma associated with Sertoli-Leydig cell tumor--a case report.

We Describe a case of ovarian serous cystadenoma having Sertoli-Leydig cell tumor, well differentiated, in the cystic septum. Well differentiated Sertoli-Leydig cell tumor coexisting with other tumor, including serous tumor, has not yet been described. In all cases of Sertoli-Leydig cell tumor with heterologous components or other tumors, the androblastomatous components are intermediately or poorly differentiated. The present case revealed a well differentiated Sertoli-Leydig cell tumor arising in a septum of serous cystadenoma, as a circumscribed nodule. With these findings, we discuss the possibility of this Sertoli-Leydig cell tumor, considered a mural nodule, which is well established in cystic common epithelial tumors of the ovary.

Adult↗
PubMed1995

Preliminary cryocrystallographic study of the mitochondrial cytochrome bc1 complex: improved crystallization and flash-cooling of a large membrane protein.

Ubiquinol-cytochrome c reductase is a crucial integral membrane protein in the mitochondrial respiratory cycle. Eleven subunits containing three cytochrome heme groups and a 2Fe-2S Rieske center make up this 240 kDa enzyme complex. Previously, many different crystal forms of the bc1 complex have displayed diffraction to as far as 4.5 A. However, rapid degradation of the protein in the X-ray beam at room temperature has obstructed the collection of a full data set from a single crystal. As slight heterogeneities between crystals severely hampered merging of data from different crystals, we sought a method to stabilize the protein crystal in the X-ray beam in order to collect a full data set from one crystal sample. To this end, water soluble protein crystals are frequently flash-cooled to cryogenic temperatures; however, there is no report of cryocrystallography for membrane proteins. In this communication, we report on a successful experiment in which flash-cooled bc1 membrane protein crystals have given rise to sustained diffraction over a 60 hour data collection period at a synchrotron source. Furthermore, we present an improved purification and crystallization protocol yielding crystals readily diffracting out to 3.3 A. These results should greatly aid in the future realization of the molecular structure of the bc1 complex as well as other membrane proteins.

Animals↗
PubMed1995

Radicicol, a protein tyrosine kinase inhibitor, suppresses the expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide and in experimental glomerulonephritis.

Two isoforms of cyclooxygenase (COX) have been identified in eukaryotic cells: a constitutively expressed COX-1 and mitogen-inducible COX-2, which is selectively expressed in response to various inflammatory stimuli. Thus, COX-2 instead of COX-1 is implicated to produce prostanoids mediating inflammatory responses. Major efforts have been focused on identifying nonsteroidal anti-inflammatory drugs (NSAIDS) which can selectively inhibit the enzyme activity of COX-2. Such NSAIDS would be more desirable anti-inflammatory agents in comparison to NSAIDS which inhibit both COX-1 and COX-2. Other than glucocorticoids, pharmacological agents which can selectively suppress the expression of COX-2 without affecting that of COX-1 have not been identified. We report here that radicicol, a fungal antibiotic, is a potent protein tyrosine kinase inhibitor, and that it inhibits the expression of COX-2 without affecting COX-1 expression in lipopolysaccharide (LPS)-stimulated macrophages with the IC50 value of 27 nM. Radicicol inhibited tyrosine phosphorylation of p53/56lyn, a Src family tyrosine kinase and one of the major tyrosine-phosphorylated proteins in LPS-stimulated macrophages. Radicicol also inhibited COX-2 expression in vivo in glomeruli of rats with experimental glomerulonephritis induced by the anti-glomerular basement membrane antibodies, in which COX-2 expression is known to be enhanced. The enzyme activity of COX-1 or COX-2 was not affected by radicicol in macrophages. Radiciciol also suppressed the COX-2 expression induced by IL-1 beta in rat smooth muscle cells. Other protein tyrosine kinase inhibitors suppressed the LPS-induced COX-2 expression in macrophages but at much higher concentrations than needed for radicicol. Radicicol did not inhibit the COX-2 expression induced by phorbol 12-myristate 13-acetate in macrophages. These results suggest that the activation of tyrosine-specific protein kinases is the proximal obligatory step in the LPS-induced signal transduction pathway leading to the induction of COX-2 expression in macrophages. The magnitude of the inhibition of COX-2 protein synthesis by radicicol was much greater than that of the steady state levels of COX-2 mRNA. These results suggest that radicicol inhibits COX-2 expression mainly at post-transcriptional steps.

Animals↗
PubMed1995

Synthesis and cellular characterization of the detransformation agent, (-)-depudecin.

BACKGROUND: (-)-Depudecin is a fungal metabolite that reverts the rounded phenotype of NIH3T3 fibroblasts transformed with v-ras and v-src oncogenes to the flat phenotype of the nontransformed parental cells. The mechanism of action of this detransformation agent is unknown. Although depudecin appears to be an excellent molecule for probing signaling pathways that regulate changes in the cytoskeletal architecture, reagents based on depudecin are not available as it has not yet been successfully synthesized. We therefore set out to synthesize (-)-depudecin. RESULTS: An asymmetric synthesis of (-)-depudecin has been developed. A cell staining assay has been used to reveal the ability of synthetic depudecin, but not several structural variants, to induce a flattened morphology in v-Ha-ras-transformed NIH3T3 cells. This assay also shows that depudecin induces an intricate network of actin stress fibers in these cells and in MG63 osteosarcoma cells and reveals the essential role of the epoxide and hydroxyl moieties in depudecin. Cycloheximide and actinomycin D inhibited the ability of depudecin to induce a morphological change, suggesting that both mRNA synthesis and de novo protein synthesis are required for depudecin-mediated suppression of the transformed phenotypes in ras-transformed cells. CONCLUSIONS: The synthetic procedure provides access to (-)-depudecin and could be readily modified to produce depudecin-related reagents for the identification of depudecin's cellular target(s). This target appears to be involved in the regulation of the assembly of the actin microfilament component of the cytoskeleton in mammalian cells.

3T3 Cells↗
PubMed1995

Morphology of ras-transformed cells becomes apparently normal again with tyrosine kinase inhibitors without a decrease in the ras-GTP complex.

Radicicol, an inhibitor of protein-tyrosine kinase, was found to cause morphological reversion of v-Ha-ras-transformed NIH3T3 fibroblasts and T24 human urinary bladder carcinoma cells that contain an activated ras mutation. The network of actin stress fibers was restored during the treatment with radicicol. A similar morphological change was observed with another protein-tyrosine kinase inhibitor, herbimycin A. Radicicol did not cause any changes in the proportion of the active GTP binding form of p21ras or its subcellular localization. These results rule out the possibility that the morphological reversion by radicicol is due to direct or indirect inhibition of the p21ras function. Cycloheximide and actinomycin D inhibited the morphological change by radicicol, suggesting that the induced transcription of a gene(s) followed by de novo protein synthesis is required for suppression of the transformed phenotype in ras-transformed cells by tyrosine kinase inhibitors.

Animals↗
PubMed1995

Association of exposure to polycyclic aromatic hydrocarbons (estimated from job category) with concentration of 1-hydroxypyrene glucuronide in urine from workers at a steel plant.

OBJECTIVES: Increased risk of lung cancer has been associated with employment in the steel industry. This association is thought to be due in part to increased concentrations of polycyclic aromatic hydrocarbons (PAHs) in air found in this work environment. Measurement of PAH metabolites in human urine provides a means of assessing individual internal dose of PAHs. This study examined the relative contribution of occupation and smoking to urinary concentration of 1-hydroxypyrene glucuronide (1-OHPG) among a group of workers at a steel plant. METHODS: Concentrations of 1-OHPG in urine from 44 workers with jobs associated with increased air concentrations of PAHs and 40 workers with jobs with low or no exposure to PAHs were measured. 20 workers in each group were not current smokers. Urinary 1-OHPG was measured by synchronous fluorescence spectroscopy after immunoaffinity chromatography specific for PAH metabolites. RESULTS: Mean (SEM) urinary 1-OHPG concentration was 2.16 (0.42) pmol/ml urine among the 44 occupationally exposed workers compared with 0.38 (0.05) among the 40 workers with no or low exposure (P < 0.0001). Mean urinary 1-OHPG concentration was 1.82 (0.41) pmol/ml urine among the 44 current smokers compared with 0.75 (0.20) among the 40 non-smokers (P < 0.005). Mean 1-OHPG concentrations in non-smokers were 0.26 (n = 20), 0.70 (n = 15), and 2.84 pmol/ml urine (n = 5) for strata of exposure to PAHs (no or low, mid, and high) based on job category; the corresponding values in smokers were 0.55 (n = 20), 0.94 (n = 12), and 4.91 pmol/ml (n = 12), respectively. Multiple linear regression showed significant differences between subjects in different PAH exposure with increased concentrations of 1-OHPG in urine. Amounts of foods containing PAHs ingested by this group of workers were relatively low and did not contribute significantly to urinary 1-OHPG concentrations. CONCLUSIONS: These results indicate that 1-OHPG is a common urinary metabolite in people with recent occupational exposure to PAHs and is associated with both job category and estimated stratum of PAH exposure.

Adult↗
PubMed1994

Enhanced cell differentiation when RB is hypophosphorylated and down-regulated by radicicol, a SRC-kinase inhibitor.

Radicicol, an inhibitor of src or src-like kinases, causes hypophosphorylation and down-regulation of the RB retinoblastoma tumor suppressor protein in HL-60 human promyelocytic leukemia cells. Both of these changes in the RB protein typically are associated with myeloid or monocytic differentiation of these cells induced by retinoic acid or 1,25-dihydroxy vitamin D3. When added with either inducer, radicicol caused the typically induced myeloid or monocytic differentiation of these cells to be accelerated. By itself radicicol caused a transient inhibition of G1 to S transit, but did not cause phenotypic conversion. The down-regulation and dephosphorylation of RB by radicicol may thus facilitate cell differentiation.

Calcitriol↗
PubMed1994

Trichostatin A induces morphological changes and gelsolin expression by inhibiting histone deacetylase in human carcinoma cell lines.

Trichostatin A (TSA) is a Streptomyces metabolite which specifically inhibits mammalian histone deacetylase at a nanomolar concentration and causes accumulation of highly acetylated histone molecules in mammalian cells. The effects of TSA on the morphology and the cell cycle of the human carcinoma cell lines, T24 and HeLa, were investigated. The morphology of T24 and HeLa cells dramatically changed and actin stress fibers reappeared during the treatment with TSA. The morphological change was not observed with chemically synthesized (S)-TSA and trichostatic acids, which are inactive to inhibit histone deacetylase. Cell cycle progression of these cells was blocked by TSA at G1 phase (HeLa) or G1 and G2 phases (T24). An RNA synthesis inhibitor, actinomycin D, and a protein synthesis inhibitor, cycloheximide, inhibited the morphological changes by TSA, suggesting that TSA induces expression of a new gene(s) followed by de novo protein synthesis, which is required for the actin microfilament reorganization. An approximately 7-fold (T24) or 12-fold (HeLa) increase in the intracellular level of gelsolin, an actin regulatory protein, was found in the cells treated with TSA for 24 h. These results suggest that gelsolin is one of the putative proteins necessary for the morphological changes of human carcinoma cells induced by TSA.

Actins↗
PubMed1993

JL1, a novel differentiation antigen of human cortical thymocyte.

Expression of a novel thymocyte differentiation antigen, JL1, defined by a monoclonal antibody (mAb) developed against human thymocytes showed a specificity for stage II double positive (CD4+CD8+) human cortical thymocytes. This antigen was not expressed at detectable levels on medullary thymocytes, mature peripheral leukocytes, bone marrow cells or on other types of tissues elsewhere in the human body. Immunohistologic analysis revealed that JL1 had a clear pattern of distribution on cortical thymocytes. Immunoprecipitation of 125I-labeled cell lysates from human thymocytes and Molt-4 leukemic cell line with anti-JL1 mAb yielded a 120-130-kD single chain glycoprotein. When immunoprecipitation of cell lysate was done after endoglycosidase F treatment, JL1 antigen was still detected by antibody but the band showed a reduction in apparent molecular mass of approximately 5 kD. This suggests that, although JL1 molecule contains carbohydrate group, this does not form a critical part of the antigenic determinant for anti-JL1 antibody. JL1 antigen appears to be the first double positive, stage-specific differentiation antigen of human thymocyte reported so far. This antigen would be a useful marker for lymphoblastic malignancy of stage II thymocyte origin and it may be involved in the thymocyte education process.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1992

Potent and specific inhibition of p60v-src protein kinase both in vivo and in vitro by radicicol.

A fungal metabolite, radicicol, with a macrocyclic ring induced the reversal of transformed phenotypes of v-src-transformed fibroblasts (Rous sarcoma virus-transformed 3Y1 rat fibroblast) at a quite low concentration of 0.1 microgram/ml. Actin stress fibers reappeared in the transformed cells after treatment with radicicol. Radicicol reduced the intracellular level of autophosphorylation of p60v-src as well as the level of other tyrosine-phosphorylated proteins in a dose-dependent manner. In vitro kinase assay revealed that radicicol effectively inhibited not only autophosphorylation but also transphosphorylation activities of purified p60v-src with a concentration producing 50% inhibition of 0.1 microgram/ml. However, radicicol showed no inhibitory effect on protein kinase C or protein kinase A. These results suggest that radicicol is a novel and specific protein-tyrosine kinase inhibitor and that the decreased level of tyrosine kinase activity of p60v-src causes reversion of transformed phenotypes of Rous sarcoma virus-transformed 3Y1 rat fibroblast. Furthermore, differentiation of Friend leukemia cells, which is one of the known characteristic phenomena associated with the inhibition of tyrosine kinase, was also induced in the concentration range of 0.05-0.5 microgram/ml, suggesting that the agent is useful for the analysis of differentiation as well as the kinase-mediated signal transduction.

Animals↗
PubMed1989

[Perceptions of spiritual nursing care nurses and nursing students].

This study was designed to clarify how nurses and nursing students perceive their clients' needs for spiritual nursing care, it's practices, and problems. The purpose was to suggest directions for the development of spiritual nursing practice. The major findings are as follows: Respondents primarily perceived spiritual nursing as nursing care designed to help terminally ill patients accept death. Many of the respondents showed a high level of awareness of spiritual nursing care and its necessity. Few of them, however, bad actual experience in spiritual care. Those with experience in spiritual nursing care tend of take either a religious approach or perceived it as the therapeutic use of the self. The greatest problem related to the practice of spiritual care was found to be lack of time. Most of nurses and nursing students were found to be well aware of the needs for spiritual nursing care but were hindered from practising it because of the lack of time. To resolve the problem it was recommended that the scope of nursing practice be readjusted and that pre- and in-service programs should be developed to further heighten nursing students' interest in spiritual nursing care.

Humans↗
PubMed1986

Effects of temperature on blood flow in facial tissues.

This study evaluated the effect of temperature on blood flow by using rubidium 86 to determine the fraction of cardiac output going to specific facial tissues of rats. Seventy-seven male Holtzman rats were divided into two groups and various subgroups. The intraoral subgroups were categorized according to the temperature of the water irrigating the oral cavity (11 degrees, 39 degrees, 41 degrees, 43 degrees, or 45 degrees C). The extraoral subgroups were categorized according to whether heat or ice was applied to the cheek of the rats and the duration of application (10 or 20 minutes). Rats were killed within 60 seconds after injection of 86Rb, and tissue samples were taken from the buccal mucosa, facial skin, masseter muscle, mandible, tongue, and maxilla. The fraction of isotope uptake in each gram of these tissues (FU/g) was then calculated. For the intraoral group, the bath temperature of 39 degrees C increased the FU/g in all tissues except masseter muscle and tongue. Higher bath temperature did not further alter the FU/g. Lowering the temperature to 11 degrees C changed the FU/g significantly only in the tongue. For the extraoral group, 20-minute application of ice was required to reduce FU/g significantly in all tissues but masseter muscle and skin. Extraoral heat application for 10 minutes increased FU/g significantly in skin and tongue, but no further change was seen after 20 minutes of application.

Animals↗
PubMed1986

Alveolar ridge maintenance with hydroxylapatite ceramic cones in humans.

The efficacy of solid cones of hydroxylapatite ceramic implanted in fresh extraction sockets for the preservation of alveolar bone was evaluated. Ten experimental subjects (70 implants) and eight control subjects (63 extractions) were treated. After extraction, hydroxylapatite ceramic cones were inserted into the sockets at least 1 mm below the alveolar crest in the experimental group. Alveolar ridge resorption was measured on lateral cephalometric radiographs, and statistical analysis was performed. The follow-up periods ranged from 12 to 24 months (mean, 20.6 months). Thirty-seven of the 70 hydroxylapatite ceramic cone implants (53%) became exposed, and 19 cones (27%) had to be removed. It was concluded that hydroxylapatite ceramic cone implants placed in fresh extraction sockets do not significantly preserve alveolar bone.

Adult↗
PubMed1985

Effects on the periodontium of vertical bone cutting for segmental osteotomy.

The periodontal response to vertical osteotomy was evaluated in seven males and ten females, aged 14-45 years (mean 26.8), who were scheduled for maxillary and/or mandibular segmental osteotomies. Plaque and gingival indices, pocket depth, clinical attachment level, width of attached gingiva, and osseous support were recorded from teeth adjacent to each osteotomy site prior to and from six months to three years after surgery. In each patient teeth numbers 3, 9, 13, 19, 25, and 29 were used as controls. There was no significant (P less than or equal to 0.05) difference between experimental and control teeth with respect to plaque, gingivitis, pocket depth, or clinical attachment level. Slightly decreased osseous support and width of attached gingiva were found adjacent to osteotomy sites. However, although these decreases were statistically significant (P = 0.005), they were not clinically very large. It was concluded that segmental osteotomies, in general, may be performed without producing significant changes in the periodontal structures.

Adolescent↗
PubMed1984

Hemangiopericytoma of the tongue: report of case.

A case of hemangiopericytoma of the tongue is reported. A comprehensive literature review regarding hemangiopericytoma of the tongue has been presented. Only ten cases of hemangiopericytoma of the tongue have been reported in the literature, including the present case, a 29-year-old male.

Adult↗