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Biomedical subjects

S R Kim

Publications and source records attributed to S R Kim.

At least 55 records · Page 3Linked to original sources

Effect of interleukin-1beta on gonadotropin-releasing hormone (GnRH) and GnRH receptor gene expression in castrated male rats.

Increasing evidence suggests that interleukin-1beta (IL-1beta) regulates luteinizing hormone (LH) release primarily through modulation of the gonadotropin-releasing hormone (GnRH) neuronal activity. This study was undertaken to elucidate the effect of IL-1beta on GnRH as well as GnRH receptor (GnRHR) gene expression in the preoptic area. IL-1beta (100 ng/rat) or saline was administered into the lateral ventricle of castrated rats. RNA samples were isolated from micropunches of the preoptic area and mediobasal hypothalamus from individual brain slices and GnRH mRNA levels in the preoptic area and GnRHR mRNA levels in the mediobasal hypothalamus were determined by competitive reverse transcription-polymerase chain reaction (RT-PCR) protocols. Serum LH concentrations were decreased from 1 h to 3 h after IL-1beta treatment, but rebounded at 5 h, while serum concentrations of follicle-stimulating hormone (FSH) and prolactin were not altered. There were no significant changes in GnRH mRNA levels from the micropunched preoptic area, while GnRHR mRNA levels from the preoptic area and mediobasal hypothalamus micropunch samples, but not in the anterior pituitary, showed a pattern similar to the serum LH profile following i.c.v. administration of IL-1beta. We then examined the effect of IL-1beta on the translational efficiency of the GnRH mRNA. After the separation and fractionation of polyribosome-associated cytoplasmic RNA from the hypothalamic fragments containing the preoptic area-anterior hypothalamic area of control (saline-treated) and IL-1beta-treated group 3 h after administration, GnRH transcript levels were examined from the each fraction. IL-1beta decreased the translational efficiency of the transcribed GnRH mRNA. These results clearly demonstrate that central administration of IL-1beta suppresses the translational activity of GnRH mRNA. Moreover, GnRHR may play an important role in the modulation of GnRH neuronal activity through GnRHR-expressing neurones (or glia) in the hypothalamus.

Animals↗

leafy hull sterile1 is a homeotic mutation in a rice MADS box gene affecting rice flower development.

Rice contains several MADS box genes. It has been demonstrated previously that one of these genes, OsMADS1 (for Oryza sativa MADS box gene1), is expressed preferentially in flowers and causes early flowering when ectopically expressed in tobacco plants. In this study, we demonstrated that ectopic expression of OsMADS1 in rice also results in early flowering. To further investigate the role of OsMADS1 during rice flower development, we generated transgenic rice plants expressing altered OsMADS1 genes that contain missense mutations in the MADS domain. There was no visible alteration in the transgenic plants during the vegetative stage. However, transgenic panicles typically exhibited phenotypic alterations, including spikelets consisting of elongated leafy paleae and lemmas that exhibit a feature of open hull, two pairs of leafy palea-like and lemma-like lodicules, a decrease in stamen number, and an increase in the number of carpels. In addition, some spikelets generated an additional floret from the same rachilla. These characteristics are very similar to those of leafy hull sterile1 (lhs1). The map position of OsMADS1 is closely linked to that of lhs1 on chromosome 3. Examination of lhs1 revealed that it contains two missense mutations in the OsMADS1 MADS domain. A genetic complementation experiment showed that the 11.9-kb genomic DNA fragment containing the wild-type OsMADS1 gene rescued the mutant phenotypes. In addition, ectopic expression of the OsMADS1 gene isolated from the lhs1 line resulted in lhs1-conferred phenotypes. These lines of evidence demonstrate that OsMADS1 is the lhs1 gene.

Amino Acid Sequence↗

TTV positivity and transfusion history in non-B, non-C hepatocellular carcinoma compared with HBV- and HCV-positive cases.

The prevalence of TT virus (TTV) and its rate of transmission through transfusion were investigated to determine its possible hepatocarcinogenic role in non-B, non-C hepatocellular carcinoma (HCC) as compared with that in hepatitis B virus (HBV)- and hepatitis C virus (HCV)-positive HCC. Its transfection route in TTV-positive cases was also studied. Serum was positive for TTV in 77.8% (7/9) of HBV-positive, 36.4% (12/33) of HCV-positive, and 63. 6% (7/11) of non-B, non-C cases of HCC. The rate of transmission through transfusion was 52.4% (11/21) in HBV-positive, 40.1% (61/152) in HCV-positive, 33.3% (2/6) in HBV+HCV-positive, and 40% (8/20) in non-B, non-C HCCs, while it was 48.3% (14/29) in TTV-positive and 39.3% (11/28) in TTV-negative cases. The association between TTV and HCC was limited, and the main route of infection of TTV was not through transfusion.

Adult↗

Dammarane derivatives protect cultured rat cortical cells from glutamate-induced neurotoxicity.

We previously reported that ginsenosides Rb1 and Rg3, dammarane glycosides, of Panax ginseng C. A. Meyer (Araliaceae), significantly attenuated glutamate-induced neurotoxicity in primary cultures of rat cortical cells. To seek more potent neuroprotective compounds, we attempted to modify the chemical structure of dammarane glycosides and obtained six derivatives, MA-11, PT-11, PT-111, POA-101, POA-111 and N-001. The neuroprotective activity of these dammarane derivatives were evaluated employing primary cultures of rat corticoid cells. The glutamate-induced neuronal cell damage was significantly reduced by a pre-treatment with protopanaxadiol, MA-11 or PT-11 at concentrations ranging from 100 nM to 10 microM. Both MA-11 and PT-11, preserved the levels of catalase and inhibited decreases in glutathione reductase in glutamate-injured cells. Furthermore, the dammarane derivatives reduced the content of intracellular peroxide in glutamate-intoxicated cells. Finally, they inhibited the formation of malondialdehyde, a compound produced during lipid peroxidation, in glutamate-insulted cells. These results show that the dammarane derivatives, MA-11 and PT-11, exert significant neuroprotective effects on cultured cortical cells by a mechanism seemingly distinct from that afforded by ginsenosides Rb1 and Rg3. As such, the dammarane derivatives may be efficacious in protecting neurons from oxidative damage caused by exposure to excess glutamate.

Animals↗

Primary peritoneal pregnancy implanted on the uterosacral ligament: a case report.

Peritoneal pregnancies are classified as primary and secondary. Primary implantation on the peritoneum is extremely rare in extrauterine pregnancy and is a potentially life-threatening variation of ectopic pregnancy within the peritoneal cavity, representing a grave risk to maternal health. Secondary abdominal pregnancies are by far the most common and result from tubal abortion or rupture, or less often, after uterine rupture with subsequent implantation within abdomen. Early diagnosis and appropriate surgical management, regardless of stage of gestation, appear to be important in achieving good results. We report a case of primary peritoneal pregnancy in a 28-year-old woman, who had severe lower abdominal pain one day before laparotomy for a preoperative diagnosis of ectopic pregnancy. The conceptus was implanted on the left uterosacral ligament. A fresh embryo of approximately 8 weeks' gestation was found in the conceptus.

Adult↗

Functional outcome following surgical treatment of metastatic tumors involving the femur.

Thirty-eight patients treated surgically for metastatic tumors of the femur were reviewed to evaluate the effects of surgical treatment on quality of life. Average age at surgery was 59 years. The most common origin site of metastatic tumors was the lung. The intertrochanteric area was involved in 14 patients, followed by the subtrochanteric area in 11, femoral neck in 7, and shaft in 6 patients. Surgery was based on the principles that tumor excision should be maximal, and to permit early postoperative ambulation, internal fixation should be rigid with cement augmentation. Types of internal fixation were applied according to lesion site to allow early ambulation and included intramedullary nailing (11), compression hip screw (9), and Rowe plates (7). Prosthetic replacement was performed in 9 patients. Average performance scores improved from 3.8 preoperatively to 2 postoperatively, based on the Functional Classification of the New York Heart Association. In 31 patients (82%), the degree of pain relief was more than a lot according to the criteria of Kaiko. Thirty-five patients survived >5 months postoperatively. In patients with a single metastatic lesion, survival was 21 months, and in patients with multiple lesions, survival was 10 months. Surgical stabilization of a pathologic lesion involving the femur resulted in improvement in the quality of life, including pain relief and early ambulation. In selected patients with a single metastatic lesion and a low-grade primary tumor, prolonged postoperative survival may be expected.

Adult↗

Down-regulation of phospholipase D during differentiation of mouse F9 teratocarcinoma cells.

Phospholipase D has been recognized as playing an important role in signal transduction in many types of cells. We investigated the expression of phospholipase D during the differentiation of F9 embryonal teratocarcinoma cells. The ADP ribosylation factor-dependent phospholipase D activity, as measured by an in vitro assay, and H2O2-induced phospholipase D activity and phospholipase D protein content in whole cells were decreased during the differentiation of F9 cells induced by a combination of dibutyryl cyclic AMP and all-trans retinoic acid. In contrast, these changes were not observed when cells were induced by retinoic acid. These results suggest that down-regulation of phospholipase D protein is associated with differentiation of F9 cells to a parietal endoderm lineage.

Animals↗

Expression of SET is modulated as a function of cell proliferation.

We explored a biological role of SET as it relates to cell proliferation and differentiation. Immunohistochemical staining demonstrated that the expression of SET was ubiquitous and diffuse over the whole embryo on gestational day 15. At a later stage of development, SET was expressed at relatively lower levels and localized to specific tissues and cells. On embryonic day 19, specific SET immunoreactivity was found in the epithelium of skin, respiratory tract, intestine, and retina as well as in muscle and cartilage. In these cells SET was stained mostly in the nucleus, which was supported indirectly by nuclear transport of enhanced green fluorescence protein-SET fusion proteins in ECV304 endothelial cells. Set mRNA expression was further confirmed in various cultured cells, including NIH 3T3 cells, L6 myoblast cells, human umbilical vein endothelial cells, and ECV304 cells. Using F9 teratocarcinoma cell lines, which were stimulated to differentiate into the two different cell lineages of parietal and visceral endoderm, we have further examined the role of SET. The expression of set mRNA and SET protein was diminished about three-fold in both differentiated endoderm cells compared to the undifferentiated F9 cells. However, when F9 cells were subjected to serum starvation, reduction of set mRNA abundance also took place at a similar level to that observed in response to differentiation. Consistent with this, quiescent L6 myoblast showed a marked downregulation of set mRNA compared to proliferating cells. These results suggest that SET is involved mainly in the regulation of cell proliferation rather than differentiation during embryonic development.

3T3 Cells↗

Overexpressed alpha3beta1 and constitutively activated extracellular signal-regulated kinase modulate the angiogenic properties of ECV304 cells.

ECV304, a spontaneously transformed cell line derived from the human umbilical vein endothelial cell (HUVEC) (Takahashi et al., 1990), has been developed as an in vitro angiogenesis model. In the present study, we further characterized the angiogenic properties of this cell line. Compared to HUVEC, ECV304 cells showed distinct features including a higher activity of cellular adhesion, slower but reproducible progression of angiogenesis on Matrigel, and resistance to apoptosis. Thus, the expression of integrin and activation of extracellular-signal regulated kinase 1/2 (Erk1/2), a downstream effector of the integrin pathway, were examined. Flow cytometry revealed that alpha3beta1 integrin was markedly upregulated in ECV304 cells, while alpha(v)beta1 and alpha5beta1 integrins were slightly downregulated. Consistent with this, the binding activity to collagen type IV and laminin, major extracellular matrices of Matrigel, was increased 1.4- and 1.9-fold in ECV304 cells, respectively. This tight binding may retard the initial stage of sprouting and migration in the angiogenesis of ECV304 cells. It has been further demonstrated that Erk1/2 is constitutively active in ECV304 cells, rendering them resistent to the inhibitory effect of PD98059 on proliferation. However, migration of both HUVEC and ECV304 cells was inhibited to a similar extent by PD98059 in a dose-dependent manner. Up to 50 microM of PD98059, no significant changes in cell binding and tubulogenesis on Matrigel was observed in ECV304 cells. In contrast, the tubulogenesis of HUVEC was severely impaired by PD98059. Elevated Erk1/2 activity in ECV304 cells was suppressed by dominant negative H-Ras, but not by cytochalasin D. These results suggest that the overexpression of alpha3beta1 integrin and the constitutive activation of Erk1/2 play a key role in the alteration of the angiogenic properties of ECV304 cells.

Apoptosis↗

The biological significance of non-enzymatic reaction of menadione with plasma thiols: enhancement of menadione-induced cytotoxicity to platelets by the presence of blood plasma.

To test the hypothesis that the non-enzymatic reaction of quinones with thiols in plasma can generate reactive oxygens (ROS), thereby leading to potentiated cellular toxicity, we have studied the effect of a representative quinone compound, menadione, on plasma isolated from rats. The experimental results are as follows: (1) menadione generated ROS via non-enzymatic reaction with protein thiols in plasma; (2) the presence of plasma increased menadione-induced cytotoxicity to platelets; (3) pretreatment of plasma with a thiol-depleting agent significantly suppressed menadione-induced ROS and cytotoxicity. These results suggest that the non-enzymatic reaction of menadione with plasma thiols could be an important process in quinone-induced cellular toxicity.

Animals↗

The dinB gene encodes a novel E. coli DNA polymerase, DNA pol IV, involved in mutagenesis.

In Escherichia coli, the dinB gene is required for the SOS-induced lambda untargeted mutagenesis pathway and confers a mutator phenotype to the cell when the gene product is overexpressed. Here, we report that the purified DinB protein is a DNA polymerase. This novel E. coli DNA polymerase (pol IV) is shown to be strictly distributive, devoid of proofreading activity, and prone to elongate bulged (misaligned) primer/template structures. Site-directed mutagenesis experiments of dinB also demonstrate that the polymerase activity of DinB is required for its in vivo mutagenicity. Along with the sequence homologies previously found within the UmuC-like protein family, these results indicate that the uncovered DNA polymerase activity may be a common feature of all these homologous proteins.

Bacterial Proteins↗

Role of actin filaments in the hatching process of mouse blastocyst.

Hatching has been suggested to occur as a result of protease-mediated lysis and the blastocoele tension. However, even if rupturing is initiated at multiple sites, interestingly only a single site is used for escape. This implies that there are several mechanisms involved in hatching. In this study, the involvement of actin filaments in mouse embryo hatching was examined. We treated mouse embryos with cytochalasin B for 12 h or 24 h at the morula, middle blastocyst, expanded blastocyst, lobe-formed blastocyst and hatching blastocyst stages, and measured the amount and distribution of actin filaments using a confocal microscope. At morula, middle blastocyst, lobe-formed blastocyst and hatching blastocyst stages embryonic development was completely arrested by cytochalasin B. However, when transferred to cytochalasin-B-free medium, the embryos resumed development and escaped the zona pellucida. In the expanded blastocysts development was almost completely inhibited by cytochalasin B, but rupturing occurred in some embryos. However, development stopped completely at the ruptured stage. Distribution of actin filaments was prominent at rupturing and hatching sites regardless of cytochalasin B treatment. The amount of actin filaments was prominent at hatching embryos compared with other developmental stages of embryos. These actin filaments were distributed intensively between the trophectodermal cells, and formed locomotion patterns. Taken together, these results suggest that not only tension and lytic enzymes are required to rupture, but the activity of actin filaments may have a crucial role in the process of hatching.

Actin Cytoskeleton↗

Inflammatory pseudotumor of the liver in a patient with chronic hepatitis C: difficulty in differentiating it from hepatocellular carcinoma.

A case of an inflammatory pseudotumor of the liver in a 75-year-old female with chronic hepatitis C whose radiologic features simulated that of hepatocellular carcinoma (HCC) is presented. On imaging studies, hypervascularity by CO2 ultrasound (US) angiography, enhancement at an early phase and isodensity at a late phase by incremental dynamic computed tomography (CT), perfusion defect by CT during arteriography (CTAP), and clinical background of hepatitis C virus (HCV) infection strongly suggested HCC. A US-guided needle biopsy revealed a mainly diffuse and polyclonal proliferation of lymphocytes positive for leukocyte common antigen (pan-lymphocyte cells), L-26 (B cell lymphocytes), and UCHL-1 (T cell lymphocytes), negative for both kappa and lambda light chains and sparsely distributed neutrophils and histiocytes. No lymphoid follicles were observed. The liver tissue around this tumor showed chronic hepatitis with mild activity and mild fibrosis. These histopathologic findings suggested that the diagnosis of inflammatory pseudotumor of the liver was tenable. As it is difficult to differentiate between inflammatory pseudotumor of the liver and HCC by imaging studies alone, supplemental biopsy, where possible, should be obtained when diagnostic imaging of tumors suggesting HCC is carried out. We emphasize that histopathology is a true gold standard in the diagnosis of this disease.

Aged↗

Protopine from Corydalis ternata has anticholinesterase and antiamnesic activities.

While screening extracts of natural products in search of anticholinesterase activity, we found that a total methanolic extract of the tuber of Corydalis ternata (Papaveraceae) showed significant inhibitory effects on acetylcholinesterase. Further fractionation of this extract using acetylcholinesterase inhibition as the parameter screened resulted in the isolation and purification of an alkaloid, protopine. Protopine inhibited acetylcholinesterase activity in a dose-dependent manner. The concentration required for 50% inhibition was 50 microM. The anti-acetylcholinesterase activity of protopine was specific reversible and competitive in manner. Furthermore, when mice were pretreated with protopine, the alkaloid significantly alleviated scopolamine-induced memory impairment. In fact, protopine had an efficacy almost identical to that of velnacrine, a tacrine derivative developed by a major drug manufacturer to treat Alzheimer's disease, at an identical therapeutic concentration. We suggest, therefore, that protopine has both anti-acetylcholinesterase and antiamnesic properties that may ultimately hold significant therapeutic value in alleviating certain memory impairments observed in dementia.

Alkaloids↗

Twelve pil genes are required for biogenesis of the R64 thin pilus.

The IncI1 plasmid R64 produces two kinds of sex pili: a thin pilus and a thick pilus. The thin pilus, which belongs to the type IV family, is required only for liquid matings. Fourteen genes, pilI to -V, were found in the DNA region responsible for the biogenesis of the R64 thin pilus (S.-R. Kim and T. Komano, J. Bacteriol. 179:3594-3603, 1997). In this study, we introduced frameshift mutations into each of the 14 pil genes to test their requirement for R64 thin pilus biogenesis. From the analyses of extracellular secretion of thin pili and transfer frequency in liquid matings, we found that 12 genes, pilK to -V, are required for the formation of the thin pilus. Complementation experiments excluded the possible polar effects of each mutation on the expression of downstream genes. Two genes, traBC, were previously shown to be required for the expression of the pil genes. In addition, the rci gene is responsible for modulating the structure and function of the R64 thin pilus via the DNA rearrangement of the shufflon. Altogether, 15 genes, traBC, pilK through pilV, and rci, are essential for R64 thin pilus formation and function.

Animals↗

The risk groups for coronary heart disease in Koreans. Assessment by distribution of serum lipid concentrations.

Coronary heart disease is the most severe form of disease caused by atherosclerosis; and there is a strong relationship between serum lipid concentrations and atherosclerosis. By decade of life, means, standard deviations and selected percentiles were calculated according to sex for serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride in 69,563 Koreans. The prevalence of dyslipoproteinemias which were related to high risk of coronary heart disease were assessed. The mean concentrations of serum total cholesterol and LDL-C in the Korean population were 5.02 mmol/l and 3.00 mmol/l. The 75th and 90th percentile concentrations of total cholesterol were 5.59 mmol/l and 6.24 mmol/l. The mean concentrations of serum triglyceride and HDL-C were 1.58 mmol/l and 1.30 mmol/l. The hyperlipoproteinemia type IV (4.8%) was the most frequent, followed by Type IIa (4.6%), hypoalphalipoproteinemia (3.3%), and type IIb (0.2%). According to the National Cholesterol Education Program Adult Treatment Panel II, 4.1% of Korean adults needed the initial drug therapy and 10.8% the initial dietary therapy for hypercholesterolemia. The age and sex-specific treatment guidelines for hypercholesterolemia would make it possible that early intervention could be applied to atherosclerosis in Korean adults.

Adolescent↗