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Biomedical subjects

K Kim

Publications and source records attributed to K Kim.

At least 181 records · Page 10Linked to original sources
PubMed2000

Sleep loss and daytime sleepiness in the general adult population of Japan.

There are few epidemiological studies on sleep loss and daytime sleepiness in the general adult population of Japan. A total of 4000 adult people, aged 20 and over, were randomly drawn from five areas of Japan, and 3030 individuals were interviewed and completed a questionnaire including information about sleep duration and sleep problems. Overall, 29% slept less than 6 h at night, 23% reported having insufficient sleep, and 6% took sleep enhancing medications. The prevalence rates were 21% for symptoms of insomnia and 15% for excessive daytime sleepiness. Symptoms of insomnia were more prevalent in the elderly, whereas young people were more likely to report short sleep duration, subjective insufficient sleep and excessive daytime sleepiness. A multiple logistic regression model revealed that excessive daytime sleepiness had significant associations with young people, short sleep duration, insomnia symptoms, subjective insufficient sleep and sleep enhancing medication use. Short sleep duration was the strongest predictor of excessive daytime sleepiness. The findings indicate that sleep loss and excessive daytime sleepiness in the Japanese adult population are common, and comparable to those reported in Western countries. Excessive daytime sleepiness in the general adult population seems more likely to be attributed to short sleep duration.

Adult↗
PubMed2000

Genetic polymorphisms of human melatonin 1b receptor gene in circadian rhythm sleep disorders and controls.

Recent studies suggest that melatonin 1b (Mel1b) receptor, as well as melatonin 1a (Mel1a) receptor, is involved in the modulation of circadian rhythms in mammals. Mutational analysis was performed in the entire coding region of the human Mel1b receptor gene using genomic DNA from sleep disorder subjects. We have identified two missense mutations, G24E and L66F. However, neither is likely to be associated with sleep disorders in our study population. One of the subjects with non-24-h sleep-wake syndrome carries missense mutations in both the Mel1a and Mel1b receptor genes.

Adult↗
PubMed2000

An epidemiological study of insomnia among the Japanese general population.

The study examined the prevalence and correlates of insomnia in a representative sample (n=3030) from the general population of Japan. Using a structured questionnaire, we found that the overall prevalence of insomnia during the preceding month was 21.4%, including difficulty initiating sleep (DIS: 8.3%), difficulty maintaining sleep (DMS: 15.0%), and early morning awakening (EMA: 8.0%). Multiple logistic regression analysis showed that older age, being unemployed, lack of habitual exercise, poor perceived health, psychological stress, and being unable to cope with stress were associated with an increased prevalence of insomnia. These findings indicate that the prevalence of insomnia in the general population of Japan is comparable to that reported in Western countries, and that insomnia is associated with multiple psychosocial factors.

Adult↗
PubMed2000

Comparative genomic hybridization studies in hydatidiform moles and choriocarcinoma: amplification of 7q21-q31 and loss of 8p12-p21 in choriocarcinoma.

Comparative genomic hybridization (CGH) was utilized to investigate genetic changes from archived cases of choriocarcinoma (n = 12) and hydatidiform moles (n = 7). Test DNA was extracted from paraffin-embedded tissues, amplified using total universal PCR, and co-hybridized with control DNA to normal metaphases. Comparative genomic hybridization findings showed chromosomal imbalances in 9 of 12 cases of choriocarcinoma. By contrast, all hydatidiform moles showed normal CGH profiles. Consistent findings in choriocarcinoma included deletion at 8p (5 cases) and amplification at 7q (4 cases). A tumor suppressor gene (e.g., N33) at 8p and/or a growth regulator at 7q could play a role in the initiation of choriocarcinoma and its progression. This is the first study showing specific alterations in choriocarcinomas by CGH, and illustrates the utility of this technique in elucidating genetic changes in gynecological tumors.

Adult↗
PubMed2000

Empty virus-like particle-based enzyme-linked immunosorbent assay for antibodies to hepatitis E virus.

Hepatitis E, an enterically transmitted non-A, non-B hepatitis, is a serious viral infection that occasionally causes large epidemics in developing countries. In developed countries, the disease only appears sporadically due to the transmission routes, and it is considered to be less important. The hepatitis E virus (HEV) cannot grow in cultured cells and no reliable assay system has ever been developed. In addition, the present diagnostic are not perfect, and actual rates of HEV infection may be underestimated. Highly purified empty virus-like particles (VLPs) of HEV have been produced by the use of a recombinant baculovirus vector in insect cells. Using these VLPs as an antigen, an enzyme-linked immunosorbent assay (ELISA) for antibodies to HEV was developed. A panel of 164 sera that were randomized and coded, and sera collected periodically from three patients with hepatitis E were used for the evaluation. The sensitivity of the assay was shown to be equal to or better than that obtained in previous research that used the same serum panel. The ELISA demonstrated that the serum IgM level of the patients was highest at the onset of the clinical illness and then rapidly decreased. In contrast, a high level of circulating IgG antibody titers lasted for more than 4 years. In Japan, a non-endemic country, the prevalence of the IgG class antibody to HEV in healthy individuals was found to range from 1.9% to 14.1%, depending on the geographical area. Only one out of 900 (0.1%) serum samples was IgM-positive. The IgM class antibody to HEV was detected in 10.8% of non-A, non-B, and non-C acute hepatitis patients in northeast China, whereas none of the patients in Korea had the IgM antibody. The ELISA utilizing the VLPs is sensitive and specific in its detection of the IgM and IgG antibodies to HEV. The ELISA is therefore useful for diagnosing HEV infection and for seroepidemiological study of hepatitis E.

Adolescent↗
PubMed2000

Magnetic resonance microscopy of the C57BL mouse brain.

With the rapid progression in gene technologies, transgenic, targeted, and chemically induced mutations in mice are continually created. The major goal of these studies is to understand and characterize the effects of genotype on anatomy, physiology, and behavior and ultimately the role of genotype in development of disease. The demand for imaging techniques with high spatial resolution potential is rising because such imaging tools would expedite anatomical phenotyping in the genetically altered mice. Magnetic resonance microscopy (MRM) is a noninvasive, inherently three-dimensional (3D) imaging technique capable of visualizing several anatomical structures in the small mouse. The 3D nature of MRM also allows for interpretation of complex spatial relationships between substructures, which is important when phenotyping anatomically. The goal of this paper is to systematically describe three major brain regions in the C57BL/6J mouse at microanatomical spatial resolution ranges using in vitro MRM. We explore different MR contrast parameters, voxel sizes, and signal-to-noise ratios to best characterize C57BL/6J mouse brain microstructure by MRM. Further, we compare all MRM images with Nissl-stained brain sections. Major findings were as follows: T2* MR images visualized several gross anatomical regions in the mouse brain but not, for example, subregions within the hippocampus. Diffusion proton stains on the other hand were superior to T2* MR images and delineated many subregions within the hippocampus proper. Finally, contrast enhancement facilitated visualization of hippocampal anatomy on the T2* MR images. The results of this study are part of an ongoing initiative at our Center focused on creating a complete C57BL/6J mouse anatomical 3D image database by MRM.

Animals↗
PubMed2000

KILLER/DR5, a novel DNA-damage inducible death receptor gene, links the p53-tumor suppressor to caspase activation and apoptotic death.

TRAIL and its emerging receptors are the newest members of the TNF receptor super-family. The activation of TRAIL receptors by ligand binding leads to apoptosis through caspase activation through an as yet unclear signaling pathway that does not require the FADD adaptor. The TRAIL receptor KILLER/DR5, is induced by DNA damage and appears to be regulated by the tumor suppressor gene p53. Both the Fas receptor and KILLER/DR5 provide potential links between DNA damage-mediated activation of the p53 tumor suppressor and caspase activation. While further evaluation of the role of TRAIL receptors in human cancer is ongoing, initial studies suggest that both KILLER/DR5 and DR4 may be targets for inactivation and that these pro-apooptotic receptors may be tumor suppressor genes. Understanding the regulation of TRAIL and its receptors may thus be beneficial for the development of novel approaches for cancer treatment. TRAIL appears to be a cancer-specific cytotoxic agent and thus offers promise as a novel therapy for cancer either through replacement of the cytokine or potentially via gene replacement. Preliminary studies suggest the potential to combine TRAIL with classical cytotoxic chemotherapeutic drugs to achieve synergistic cell killing.

Animals↗
PubMed2000

A mouse thymic stromal cell line producing macrophage-colony stimulating factor and interleukin-6.

A thymic stromal cell line, TFGD, was established from a thymic tumor mass developed spontaneously in p53 knock out mouse, and was found to produce cytokines that could induce bone marrow hematopoietic stem cells (HSCs) to differentiate into macrophages. The cytokines produced by the TFGD line were assessed by immunoassays. High level of macrophage-colony stimulating factor (M-CSF) and interleukin (IL)-6 was detected in the TFGD-culture supernatant, whereas granulocyte/macrophage-colony stimulating factor (GM-CSF), IL-3, IL-4, IL-5, IL-13, or interferon (IFN)-gamma was undetectable. Blocking experiments showed that anti-M-CSF monoclonal antibody could neutralize the differentiation-inducing activity shown by the TFGD-culture supernatant. Dot blot analysis of the total RNA isolated from the cultured fetal thymic stromal cells showed that M-CSF transcripts were expressed in the normal thymus. These observations, together with the earlier finding that M-CSF plus IL-6 is the optimal combination of cytokines for the induction of macrophage differentiation from HSCs in vitro, may indicate that thymic macrophages could be generated within the thymus by cytokines involving M-CSF.

Animals↗
PubMed2000

Cellular FLIP is expressed in cardiomyocytes and down-regulated in TUNEL-positive grafted cardiac tissues.

OBJECTIVE: c-FLIP is a natural homologue of caspase 8, and may antagonize activation of death pathways mediated by FADD. c-FLIP is highly expressed in the heart, and a recent report suggests that c-FLIP may protect against certain types of myocyte death. The present study was designed to define the expression patterns of c-FLIP in the heart. METHODS: The expression pattern of c-FLIP in end-stage human hearts, and rat cardiomyocyte grafting models was analyzed by in situ hybridization, immunohistochemistry and TUNEL assay. In addition, to determine whether Fas-dependent pathway is active in cardiomyocytes in vitro, we examined whether activated monocytes can kill neonatal cardiomyocytes in a co-culture system. RESULTS: c-FLIP mRNA and protein were abundantly expressed in normal cardiomyocytes from failing human heart. In animal models, c-FLIP protein was absent in TUNEL-positive grafted cardiomyocytes. Double staining demonstrated that c-FLIP-positive cells rarely had fragmented DNA, while TUNEL-positive cells rarely contained c-FLIP. Finally, activated monocytes induced death of neonatal rat cardiomyocytes via the Fas/FasL system. CONCLUSIONS: Loss of c-FLIP expression correlates with cardiomyocyte cell death. We hypothesize that diminished c-FLIP expression may predispose cardiomyocytes to apoptotic death.

Adult↗
PubMed2000

Tyrosine analogues as alternative substrates for protein tyrosine kinase Csk: insights into substrate selectivity and catalytic mechanism.

Protein tyrosine kinases are critical enzymes in cell signal transduction but relatively little is known about the molecular recognition of the tyrosine substrate by these enzymes. Details of tyrosine substrate specificity within the context of a short peptide were investigated for protein tyrosine kinase Csk. It was found that aryl ring functional group substitutions the size of methyl group or smaller were generally well tolerated by the protein tyrosine kinase Csk whereas larger groups caused a decline in substrate efficiency. Extension of the phenol from the peptide backbone by a single methylene was acceptable for phosphorylation whereas removal of a methylene nearly abolished reactivity. Only the L-tyrosine derivative was processed. A negative charge ortho to the phenol hydroxyl was incompatible with substrate reactivity, consistent with previous pH rate profiles which indicated the importance of the neutral phenol. Overall, these studies confirmed the interpretation of a previous linear free energy relationship analysis which suggested that the enzyme followed a dissociative transition state mechanism.

CSK Tyrosine-Protein Kinase↗
PubMed2000

Scope, limitations and mechanistic aspects of the photo-induced cross-linking of proteins by water-soluble metal complexes.

BACKGROUND: Chemical cross-linking is a valuable tool with which to study protein-protein interactions. Recently, a new kind of cross-linking reaction was developed in which the photolysis of associated proteins with visible light in the presence of ammonium persulfate and tris(2,2'-bipyridyl)ruthenium(II) dication or palladium(II) porphyrins results in rapid and efficient covalent coupling (Fancy, D.A. & Kodadek, T. (1999). Proc. Natl. Acad. Sci. USA 96, 6020-6024 and Kim, K., Fancy, D.A. & Kodadek, T. (1999). J. Am. Chem. Soc. 121, 11896-11897). Here, mechanistic and practical aspects of the reaction of importance for its application to biochemical problems are examined. RESULTS: It is shown that the photo-initiated cross-linking chemistry can be optimized for the analysis of protein-protein interactions in crude cell extracts. A number of commonly used epitope or affinity tags survive the reaction in functional form, allowing the simple visualization of the cross-linked products, or their isolation. It is shown that very little light-independent oxidation of protein residues occurs and that significant perturbation of complexes of interest prior to the brief photolysis period does not occur. Finally, evidence is presented that is consistent with a mechanistic model in which ammonium persulfate functions simply as an electron acceptor, facilitating the generation of the key high valent metal complex from the photoexcited species by electron transfer. In the absence of an electron acceptor, a much lower efficiency reaction is observed that appears to involve products resulting from reaction of the excited state metal complex with molecular oxygen. CONCLUSIONS: These results provide useful practical information for chemists and biochemists who may wish to employ this new cross-linking chemistry for the analysis of protein complexes. They also shed new light on the mechanism of this interesting reaction.

Bacterial Proteins↗
PubMed2000

Role of study strategy in recall of mixed lists of common and rare words.

Experiment 1 confirmed previous findings that common words are more recallable than are rare words when the 2 kinds of words are presented in separate lists but not when they are presented in the same list. Experiment 2 showed much the same pattern when an orienting task was performed during word presentation. In Experiment 3 common words were found to be more recallable than rare words even for mixed lists when no warning was given of the memory test, although the effect was less pronounced than for pure lists. In Experiment 4 stronger measures were taken to preclude anticipation of the memory test, and the effect of word commonness was found to be just as pronounced with mixed lists as it was with pure lists. It was suggested that lists are studied in a way believed to optimize recall and that mixed lists foster a strategy of favoring the rare words.

Adult↗
PubMed2000

Enhancement of adenoviral transduction with polycationic liposomes in vivo.

Although the high transfection efficiency with adenovirus in vitro is well documented, it is still not clear whether adenoviral vectors are effective in vivo in solid tumor models. In our preliminary experiment, transduction of tumor tissue was limited to just around the injection site after intratumoral injection of the adenoviral vector. To improve the transduction efficiency in vivo, we tried a combination of adenoviral vector and liposome in our animal model. Adenovirus carrying human placental alkaline phosphatase (AdALP) and Lipofectamine or 1,3-di-oleoyloxy-2-(6-carboxyspermyl)-propylamide were used as a marker gene and the cationic liposome, respectively. A >15-fold increase in the transfection efficiency was observed in CT26 tumor cell lines with the combination of AdALP adenovirus carrying murine granulocyte-macrophage colony-stimulating factor (AdmGM-CSF), and liposome compared with adenovirus alone, showing the feasibility of the combination treatment. In the animal model, with the combination of liposome and AdALP, deeper and wider distribution of the marker gene in the tumor mass was shown. We conclude that the limitations of direct application of adenoviral vectors in a solid tumor model could be overcome by the use of cationic liposomes. This approach will facilitate the more effective delivery of adenoviral vectors in a clinical trial setting.

Adenocarcinoma↗
PubMed2000

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↗
PubMed2000

Effects of small dose of brotizolam on P300.

Nine healthy men (mean age, 22.2 years) participated in two experimental sessions cross-overed randomly in a double blind manner; one with a placebo and the other with 0.125 mg of brotizolam (BTZ) administered in the morning. Resting electroencephalogram and event-related potential under oddball paradigm was recorded before and 1, 2, 4, 6 and 8 h after the administration. Mean 30-msec bin amplitude from 240 msec to 450 msec after the stimulus was compared between placebo and drug sessions in order to observe P300. Brotizolam reduced the amplitude of P300 at 6 h after administration. It was noted that the effects of BTZ were most marked at Fz.

Adult↗
PubMed2000

Melatonin treatment for circadian rhythm sleep disorders.

This study investigated the effects of melatonin administration on circadian rhythm sleep disorders, and aimed to clarify clinical characteristics of melatonin responders. The subjects were 46 patients with circadian rhythm sleep disorders: 30 Delayed Sleep Phase Syndrome (DSPS) and 16 non-24 h sleep-wake syndrome (non-24). Patients took 0.3-1.0 mg of melatonin 5, 3 and 1 h before habitual bedtime. Seventeen patients responded to melatonin (12 DSPS, five non-24). Comparison of clinical background between responders and non-responders revealed that the responders were characterized by short total sleep time and later onset age of clinical symptoms.

Administration, Oral↗
PubMed2000

The relationship of the glenoid fossa to the functional occlusal plane.

The geometric relationship of the functional occlusal plane to the center of the glenoid fossa, as seen in the sagittal view, is described for males and females from age 7 through 25 years. This relationship is fully described by the distance from the geometric center of the glenoid fossa perpendicular to the functional occlusal plane (L, in millimeters) and its angulation (theta, in degrees) relative to a constructed Frankfort horizontal (SN-7 degrees ). Regression formulas with 95% confidence levels are described for L and theta for both genders combined. The differences between genders were found to be statistically insignificant. No correlation was found between these dimensions relative to the presence of temporomandibular joint dysfunction symptoms. A statistically significant difference in both L and theta was found in males who exhibited a Class III relationship compared with males exhibiting a Class II relationship.

Adolescent↗