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Biomedical subjects

J M Kim

Publications and source records attributed to J M Kim.

At least 91 records · Page 5Linked to original sources

Drosophila Mediator complex is broadly utilized by diverse gene-specific transcription factors at different types of core promoters.

To decipher the mechanistic roles of Mediator proteins in regulating developmental specific gene expression and compare them to those of TATA-binding protein (TBP)-associated factors (TAFs), we isolated and analyzed a multiprotein complex containing Drosophila Mediator (dMediator) homologs. dMediator interacts with several sequence-specific transcription factors and basal transcription machinery and is critical for activated transcription in response to diverse transcriptional activators. The requirement for dMediator did not depend on a specific core promoter organization. By contrast, TAFs are preferentially utilized by promoters having a specific core element organization. Therefore, Mediator proteins are suggested to act as a pivotal coactivator that integrates promoter-specific activation signals to the basal transcription machinery.

Amino Acid Sequence↗

Phenotypic variation of a Thr704Met mutation in skeletal sodium channel gene in a family with paralysis periodica paramyotonica.

OBJECTIVES: Patients with paralysis periodica paramyotonica exhibit a clinical syndrome with characteristics of both hyperkalaemic periodic paralysis and paramyotonia congenita. In several types of periodic paralysis associated with hyperkalaemia, mutations in the skeletal muscle sodium channel (SCN4A) gene have been previously reported. Phenotypic variations of mutations in SCN4A, however, have not been described yet. The present study aimed to evaluate genetic variations in a family with clinical and electrophysiological characteristics of paralysis periodica paramyotonia. METHODS: Seven members of a family affected with symptoms of paralysis periodica paramyotonia were studied by electrophysiological and genetic analyses. There were increased serum potassium concentrations in four members during paralytic attacks induced by hyperkalaemic periodic paralysis provocation tests. Short exercise tests before and after cold immersion were carried out in four patients to distinguish electrophysiological characteristics of hyperkalaemic periodic paralysis and paramyotonia. Sequencing analyses of SCN4A were performed on one patient and a normal control to identify polymorphisms. Restriction fragment length polymorphism (RFLP) analysis was then performed at the identified polymorphic sites. RESULTS: Electrophysiological studies showed both exercise sensitivity and temperature sensitivity. Compound motor action potential (CMAP) amplitudes were decreased (7.3%-28.6%) after short exercise tests. The CMAP amplitudes were even more severely decreased (21.7%-56.5%) in short exercise tests after cold exposure. Three polymorphic sites, Gln371Glu, Thr704Met, and Aspl376Asn were identified in SCN4A. RFLP analyses showed that all affected patients carried the Thr704Met mutation, whereas unaffected family members and a normal control did not. CONCLUSION: Phenotypic variation of the Thr704Met mutation, which was previously reported in patients with hyperkalaemic periodic paralysis, is described in a family affected with paralysis periodica paramyotonia.

Adult↗

Spatial and temporal distribution of Bax in rat spinal cord during normal aging.

Amytrophic lateral sclerosis is characterized by relentlessly progressive degeneration of spinal cord motor neurons. During the disease, the bcl-2 family genes have been reported to alter their expression levels. To understand the meaning of these changes, the expression pattern of Bax in rat spinal cord and its changing pattern during normal aging were investigated by immunohistochemical staining. Spatial expression of the protein showed a diffuse distribution pattern with immunoreactivity more prominent in the anterior hom. With advancement of age, the cell densities of Bax-positive cells tended to increase. The increasing expression of Bax might be positively associated with amyotrophic lateral sclerosis. This work demonstrates for the first time how Bax expression changes in rat spinal cord during normal aging.

Age Factors↗

Human ovarian cancer and cisplatin resistance: possible role of inhibitor of apoptosis proteins.

The inhibitor of apoptosis proteins (IAPs) constitutes a family of highly conserved apoptosis suppressor proteins that were originally identified in baculoviruses. Although IAP homologs have recently been demonstrated to suppress apoptosis in mammalian cells, their expression and role in human ovarian epithelial cancer and chemotherapy resistance are unknown. In the present study we used cisplatin-sensitive and -resistant human ovarian surface epithelial (hOSE) cancer cell lines and adenoviral antisense and sense complementary DNA expression to examine the role of IAP in the regulation of apoptosis in human ovarian cancer cells and chemoresistance. Antisense down-regulation of X-linked inhibitor of apoptosis protein (Xiap), but not human inhibitor of apoptosis protein-2 (Hiap-2), induced apoptosis in cisplatin-sensitive and, to a lesser extent, in -resistant cells. Cisplatin consistently decreased Xiap content and induced apoptosis in the cisplatin-sensitive, but not cisplatin-resistant, cells. Hiap-2 expression was either unaffected or inhibited to a lesser extent. The inhibition of IAP protein expression and induction of apoptosis by cisplatin was time and concentration dependent. Infection of cisplatin-sensitive cells with adenoviral sense Xiap complementary DNA resulted in overexpression of Xiap and markedly attenuated the ability of cisplatin to induce apoptosis. Immunohistochemical localization of the IAPs in hOSE tumors demonstrated the presence of Xiap and Hiap-2, with their levels being highest in proliferative, but not apoptotic, epithelial cells. These studies indicate that Xiap is an important element in the control of ovarian tumor growth and may be a point of regulation for cisplatin in the induction of apoptosis. These results suggest that the ability of cisplatin to down-regulate Xiap content may be an important determinant of chemosensitivity in hOSE cancer.

Aged↗

Caspase-3 and caspase-activated deoxyribonuclease are associated with testicular germ cell apoptosis resulting from reduced intratesticular testosterone.

The purpose of the present study was to examine the possible involvement of caspase-3 and caspase-activated deoxyribonuclease in rat testicular germ cell apoptosis resulting from reduced intratesticular testosterone concentration. Adult Sprague Dawley rats received LH-suppressive testosterone- and estradiol-filled SILASTIC capsules of 2.5 and 0.1 cm, respectively, a regimen known to rapidly reduce testosterone production by the testes and to produce azoospermia within 8 wk. Germ cell internucleosomal DNA cleavage increased compared with control levels by 1 wk postimplantation and increased further through 4 wk. In situ terminal deoxynucleotidyltransferase-mediated deoxy-UTP nick end labeling revealed that spermatocytes represented the predominant apoptotic cell type. Modest immunoreactivity for active caspase-3 was localized to the cytoplasm or perinuclear region of the germ cells of control testes. After testosterone and estradiol administration, however, intense staining for caspase-3 was localized to the nuclei of spermatocytes. Western blotting revealed significantly increased caspase-3 cleavage (activation) in nuclei isolated from germ cells after rats were administered testosterone and estradiol. Cleavage of the caspase-3 substrate protein, poly(ADP-ribose) polymerase, was seen after testosterone and estradiol treatment. Additionally, the caspase-activated deoxyribonuclease protein content was significantly increased in germ cells after rats were administered testosterone and estradiol, and caspase-activated deoxyribonuclease immunoreactivity was localized to the nuclei of apoptotic spermatocytes. Taken together, these results indicate that germ cell apoptosis resulting from a reduced intratesticular testosterone concentration is caspase-3 activation dependent and suggest that the translocation of active caspase-3 and caspase-activated deoxyribonuclease to the nucleus may be involved in the induction of germ cell apoptosis.

Animals↗

Effects of insulin and antioxidant on plasma 8-hydroxyguanine and tissue 8-hydroxydeoxyguanosine in streptozotocin-induced diabetic rats.

Cumulating evidence suggests that enhanced oxidative stress may contribute to diabetic angiopathy. The levels of 8-hydroxydeoxyguanosine (8-OHdG) and 8-hydroxyguanine (8-OHG), indicators of oxidative DNA damage, in tissue or body fluid are increased in diabetic patients. However, it is unclear whether plasma 8-OHG correlates with tissue 8-OHdG and whether insulin or antioxidant treatment reduces plasma 8-OHG in diabetic state. In this study, we measured the 8-OHG levels in plasma as well as the 8-OHdG levels in liver and kidney in streptozotocin-induced diabetic rats (DR) treated with insulin (DR+I), insulin and probucol (DR+I/P), or insulin and vitamin E (DR+I/E). There was a correlation between plasma 8-OHG levels and tissue 8-OHdG levels (plasma 8-OHG vs. liver 8-OHdG: r = 0.64, P < 0.001; plasma 8-OHG vs. kidney 8-OHdG: r = 0.38, P = 0.06). DR had levels of plasma 8-OHG that were three times higher than control rats (CR), whereas they had levels of tissue 8-OHdG that were approximately 1.5-2 times higher. Plasma 8-OHG levels in DR were almost normalized by insulin treatment, although insulin partially corrected hyperglycemia (plasma 8-OHG: CR 3.3 +/- 2.7 pmol/ml; DR 10.4 +/- 2.3 pmol/ml, P < 0.05 vs. CR; DR with insulin 3.6 +/- 1.0 pmol/ml, P < 0.05 vs. DR). However, tissue 8-OHdG levels in DR were significantly decreased by combined treatment with insulin and antioxidant (probucol or vitamin E), but not by insulin treatment alone. This data suggests that plasma 8-OHG could be a useful biomarker of oxidative DNA damage in diabetic subjects. The mechanism of differential response of plasma 8-OHG and tissue 8-OHdG to insulin and antioxidant treatment remains to be elucidated.

8-Hydroxy-2'-Deoxyguanosine↗

Malignant solitary fibrous tumor of the pleura causing recurrent hypoglycemia; immunohistochemical stain of insulin-like growth factor i receptor in three cases.

We present three cases of malignant solitary fibrous tumors of the pleura (SFTP) that produced recurrent hypoglycemia. Removal of the tumors produced normoglycemia. The tumors were well circumscribed and lobulated, and consisted of firm masses weighing 1,150 g to 1,450 g with the greatest diameter of 15 to 20 cm. The tumors were composed of spindle cells in fascicles or in a haphazard arrangement and were highly cellular and mitotically active (3-8 mitoses/10 high-power fields), showing histologically malignant features. Ultrastructurally, fibroblastic features of the tumor cells were present. Insulin-like growth factors (IGF) have been implicated in the presentation of hypoglycemia. The serum insulin and C-peptide levels were not elevated. Serum IGF-I levels were also low with values of 97.4, 157.1 and 51.9 ng/mL (ref. 125-317 ng/mL), respectively. However, tumor cells were strongly positive for IGF-I receptor on immunohistochemical analysis. It is tempting to speculate that IGF-I contributes to the hypoglycemia, even though the circulating levels were low.

Aged↗

Multiple intracranial aneurysms associated with branchio-oto-dysplasia.

Branchio-oto-dysplasia is characterized by abnormalities of embryonic branchial arch system and deafness inherited as autosomal dominant with variable gene expression. We present a rare case of multiple intracranial aneurysms associated with branchio-oto-dysplasia. A 40-yr-old man with severe headache presented as spontaneous subarachnoid hemorrhage on brain computed tomographic scan. The patient also manifested clinical features of branchio-oto-dysplasia and right hemifacial hypoplasia. Carotid angiogram confirmed an aneurysm in the anterior communicating artery. Intraoperative findings demonstrated multiple aneurysms in the anterior communicating artery and in the left posterior communicating artery, which were clipped successfully. Postoperative course was uneventful. This condition has not been reported previously. We also reviewed literatures to discuss whether the intracranial aneurysm was as a coincidental finding or a part of this malformation.

Adult↗

Frequencies of fetal chromosomal abnormalities at prenatal diagnosis: 10 years experiences in a single institution.

We present frequencies of fetal chromosomal abnormalities in 4,907 prenatal cytogenetic examinations at Samsung Cheil Hospital from 1988 to 1997 for 10 yr duration. Prenatal karyotypes were undertaken in 3,913 amniotic fluid samples, 800 chorionic villi samples, and 194 percutaneous umbilical blood samples. The frequency of fetal abnormal karyotypes was 3.1% (150 cases). Numerical chromosome abnormalities were 87 cases (1.8%) and structural aberrations of chromosomes were 63 cases (1.3%). In the numerical chromosomal abnormalities, the frequency of trisomy 21 was by far the highest (36 cases), followed by trisomy 18 in 22 cases and sex chromosome aneuploidies in 19 cases. In the structural chromosomal aberrations, 5 cases had the inversions in chromosome 2, 7, 17, and Y. Chromosomal deletions in 6 cases and additions in 4 cases were analysed. Of the remaining 47 translocation in abnormal fetuses, reciprocal translocation was in 26 cases and Robertsonian translocation in 21 cases. Among them, 41 cases were balanced translocation and 6 were unbalanced. Thirty five cases of translocation were inherited from one of the parents. Four had de novo chromosome rearrangements, and 8 cases were unknown.

Chromosome Aberrations↗

Evaluation of a simultaneous HIV antigen and antibody detection test in Korean population.

Current diagnosis of human immunodeficiency virus (HIV) infection relies on the detection of anti-HIV antibodies by enzyme-linked immunosorbent assay (ELISA). Recently, kits detecting both p24 antigenemia and anti-HIV/anti-HIV2 antibodies have been developed. Thus, it is necessary to compare those kits developed as such. The aim of this study was to evaluate the diagnostic efficiency of a simultaneous detection test of p24 antigen and anti-HIV1/2 antibodies in a low prevalence area. Eight hundred and four randomly selected sera proven negative for HIV infection and 110 sera from 54 patients diagnosed as HIV infected, obtained between 1999 and 2000, were used for this study. One commercial lot of panels composed of consecutive sera obtained from known HIV-infected patient was included. Anti-HIV1/2 antibodies were detected by two different commercial ELISA kits, one from Korean and the other from German manufacturer. P24 antigen test was performed by ELISA. The simultaneous HIV antigen and antibody detection test was carried out. In the meantime, HIV RNA PCR and anti-HIV and anti-HIV2 western blot assays were also performed to confirm the test results in cases the test results didn't agree. The simultaneous detection kit showed 100% sensitivity and 99.6% specificity. Furthermore, the test displayed the possibility of earlier diagnosis than conventional anti-HIV1/2 ELISA with the results obtained from a group of consecutive panel sera infected with HIV. From these results, we concluded that the simultaneous HIV antigen and antibody detection test can be applied as a substitute clinical screening test in the place of conventional anti-HIV1/2 ELISA, and there is the probable benefit of early diagnosis.

Enzyme-Linked Immunosorbent Assay↗

Comparison of the reverse transcription-PCR with the branched DNA assay for measurement of human immunodeficiency virus type 1 RNA levels in plasma of Korean patients.

Viral load testing of human immunodeficiency virus (HIV) is an essential tool for initiating and monitoring the antiretroviral therapy for HIV patients. To this end, several methods including polymerase chain reaction (PCR), branched DNA (bDNA), nucleic acid sequence based amplification assay (NASBA) and internally controlled virion PCR (ICV PCR) have become available. Of these methods, the standard reverse transcription-PCR (RT-PCR) assay has been widely used in Korea. However, no comparison study has been performed among the various detection methods currently used in Korean patients. We evaluated the correlation and agreement between the PCR and the branched DNA (bDNA) assay for measurement of HIV RNA in Korean patients. Eighty randomly selected samples from HIV-1-seropositive patients visiting Yonsei Medical Center Severance Hospital were studied. We found that these assays show good agreement, have a reliable correlation (r = 0.92, mean difference in log10 copies/ mL +/- 2 standard deviation = 0.098 +/- 0.805) and produce values whose relationship is given by the following equation: log10v3 bDNA = -0.3405 + 1.0601 x log10RT-PCR. Thus, we conclude that these two methods may allow direct comparison of the results obtained from different assay systems.

DNA↗

Vascular endothelial growth factor - its relation to neovascularization and their significance as prognostic factors in renal cell carcinoma.

Angiogenesis is a series of processes that include endothelial proliferation, migration and tube formation. Vascular endothelial growth factor (VEGF) is regarded as a potent mediator of angiogenesis, vascular permeability and tumor cell growth in renal cell carcinoma. This study was designed to evaluate the expression of VEGF and the microvessel count (MVC) and to determine their prediction efficacies for prognosis in renal cell carcinoma. The relationship between the expression of VEGF and MVC were evaluated immunohistochemically in 50 patients with renal cell carcinoma who received a radical nephrectomy at Wonju Christian Hospital between 1989 and 1997. Microvessels were identified by immunostaining endothelial cells for CD-31 antigen. The mean follow-up was 96 months (3 - 133 months). Overall 5-year survival rate was 71.5%. VEGF was expressed in the tumor cell cytoplasm. Of the 50 tumors, 23 (46%) were weak to strongly positive for VEGF but 27 (54%) were unreactive. The respective 5-year survival rates for patients with positive and negative expressions of VEGF were 70% and 73% (p > 0.05). The overall mean MVC was 13.4 in a 400x field. Mean MVCs were significantly higher in VEGF-positive tumors (17.6 +/- 12.1) than in VEGF-negative tumors (9.9 +/- 5.4), and the MVCs of the high vascular density group and the low vascular density groups were significantly different. The 5-year survival rates of patients with high vascular density and low vascular density were 59% and 86%. The median survival period for patients with MVCs higher than or equal to 10 vessels/field was 85 months, whereas for those with MVCs lower than 10 vessels/field the median survival time was 102 months. These results suggest that MVC may be a better prognostic factor in renal cell carcinoma than the expression of VEGF.

Adult↗

Urethral diverticulo-rectal fistula in AIDS.

A 41-year-old heterosexual African man was evaluated for persistent urethral discharge, pneumaturia and watery diarrhea. Radiographic and endoscopic procedures established the diagnosis of a rectourethral fistula. The differential diagnosis of an acquired rectourethral fistula and the significance of AIDS are discussed.

Acquired Immunodeficiency Syndrome↗

Enrichment media for isolation of Campylobacter jejuni from inoculated ground beef and chicken skin under normal atmosphere.

The efficiency of Hunt broth containing Oxyrase was compared with the gas replacement method for detection of Campylobacter jejuni in inoculated ground beef and chicken skin. Five strains of C. jejuni were inoculated individually into samples and cultured with various media under conditions generated by either flushing with a mixture of gases or supplementing with Oxyrase. Oxyrase media added with 7% lysed blood, 2.5% charcoal, or 6% ground cooked meat were compared with examinations from chicken skin samples. Campylobacter counts from enrichments were performed at 6, 12, 20, and 28 h of incubation. From inoculated ground beef, counts at 20 h increased by 4 to 7 log CFU/ml depending on strains and initial concentration of inocula. The efficiencies of Hunt medium using gassing and those with Oxyrase added were similar (P > 0.05). Broth containing 0.15 U/ml of Oxyrase without blood effectively supported the growth of all strains (P > 0.05). From inoculated chicken skin, 20-h incubation counts increased by 3.0 to 7.5 log CFU/ml for the gassing method and by 2.7 to 7.3 log CFU/ml for supplementation with 0.6 U/ml of Oxyrase and blood. The addition of 7% lysed sheep blood provided better Campylobacter growth than supplementing with 2.5% charcoal or 6% ground cooked meat. Enrichment media incorporating with Oxyrase is a simple, convenient, and time-saving method to replace flushing with mixed gas for isolation of Campylobacter jejuni.

Animals↗

Destruction of Escherichia coli O157:H7 and Salmonella enteritidis in cow manure composting.

Application of cow manure and composted manure in agricultural practice could potentially cause contamination of foodstuffs with pathogenic bacteria such as Salmonella Enteritidis and Escherichia coli O157:H7. In this study, rifampicin-resistant (RifR) E. coli O157:H7 and Salmonella Enteritidis at a level of 7 log CFU/g of raw compost feed were used to determine the effect of a bench-scale composting system on their survival. RifR E. coli O157:H7 was not detected after 72 h of composting at 45 degrees C, and RifR Salmonella Enteritidis was not detected after 48 h. The use of selective media for enrichment failed to recover in the composting samples held at 45 degrees C for 96 h. However, the pathogens showed no change in bacterial numbers when the composting system was held at room temperature. Thus, properly composted manure can be safely used in food crop production while minimizing the likelihood of microbial contamination.

Animals↗

Role of prostaglandins in the suppression of apoptosis in hen granulosa cells by transforming growth factor alpha.

Although transforming growth factor alpha (TGF-alpha) is known to be an important survival factor for granulosa cells, the cellular and molecular mechanisms involved are uncertain. The purpose of the present study was to investigate the possible involvement of prostaglandins in the anti-apoptotic action of TGF-alpha. Hen granulosa cells from healthy prehierarchical follicles (2-6 mm) cultured in serum-free medium underwent spontaneous apoptosis as demonstrated by DNA fragmentation and nuclear chromatin condensation. TGF-alpha (20 ng ml(-1)) stimulated maximum synthesis of prostaglandins (PGE and PGF) in granulosa cells and completely inhibited serum deprivation-induced apoptosis. The addition of an inhibitor of cyclooxygenase (COX; N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide (NS398) or ibuprofen) or phospholipase A(2) (PLA(2); aristolochic acid, 2-p-amylcinnamoyl amino-4-chlorobenzoic acid (ONO-RS-82) or arachidonyl triflouro methyl ketone (TFMK)), to the culture medium markedly suppressed the TGF-alpha-induced prostaglandin synthesis and significantly increased granulosa cell apoptosis. The apoptotic effect of NS398 and aristolochic acid was completely inhibited by exogenous prostaglandins (PGF(2 alpha), PGE(1), PGE(2)) and arachidonic acid, respectively. However, exogenous prostaglandins failed to inhibit the PLA(2) inhibitor-induced apoptotic DNA fragmentation, implying that in addition to prostaglandins, arachidonic acid or leukotrienes may be important in transducing the anti-apoptotic action of TGF-alpha. In the absence of exogenous TGF-alpha, prostaglandins had no significant influence on granulosa cell apoptosis induced by serum withdrawal. These findings indicate that prostaglandin synthesis is a necessary, but not sufficient, event in the suppression of granulosa cell apoptosis by TGF-alpha. Whether arachidonic acid or leukotrienes are important in the anti-apoptotic action of TGF-alpha in hen granulosa cells remains to be determined.

Alprostadil↗