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Biomedical subjects

H M Kim

Publications and source records attributed to H M Kim.

At least 289 records · Page 16Linked to original sources

Expression of osteopontin messenger RNA by macrophages in atherosclerotic plaques. A possible association with calcification.

Calcification is a common complication in atherosclerosis. As osteopontin (OPN) and osteonectin (ON) are not only involved in the physiological but also the pathological calcification of tissues, we examined the expression of OPN and ON messenger (m)RNAs in normal and atherosclerotic human aortas. By Northern blotting, the OPN mRNA expression was related to the severity of the atherosclerosis. However, ON mRNA expression decreased with the development of atherosclerosis. By a combination of in situ hybridization and immunohistochemistry of serial sections, the macrophages surrounding the atheromatous plaques were identified as the OPN mRNA-expressing cells. The ON mRNA-expressing cells in aortas of a newborn baby and a 3-year-old boy were medial smooth muscle cells, but in aortas of adults, smooth muscle cells that had invaded the intima were found to express ON mRNA. As OPN mRNA-expressing macrophages surrounded the atheromatous plaques, and as the level of OPN mRNA expression increased as atherosclerosis advanced, it is possible that OPN plays a role in the calcification of atheromatous plaques.

Aged↗

Localization and developmental expression of a novel protein kinase C delta gene.

The expression and localization of a novel protein kinase C delta (nPKC delta) mRNA were investigated using Northern blotting and in situ hybridization in the developmental process of mouse brain. In adult mice, nPKC delta was abundantly expressed in the thalamus, moderately in the pons and the cerebellum, but faintly in the cerebral cortex and the spinal cord. By in situ hybridization, the signals were observed specifically at the sensory and motor relay nuclei of the thalamus, the dorsal cochlear nuclei of the pons, and the molecular layer of the cerebellum. When developmental changes in the expression of nPKC delta gene were analyzed by in situ hybridization, it was not detectable in embryonic and neonatal brains, very weakly expressed in the thalamus in the first week, and highly expressed at two weeks of age. These results suggest that the gene expression of nPKC delta is strictly controlled by both the cell type and the developmental process.

Animals↗

Spatial expression of genes encoding c-kit receptors and their ligands in mouse cerebellum as revealed by in situ hybridization.

Expression of mRNA for c-kit receptors and their ligands was examined in the cerebellum of mice by in situ hybridization technique. The c-kit receptors were expressed in the molecular layer of the cerebellum and the ligands for the c-kit receptors were detected at the boundary of molecular and granular layers. The expression of the c-kit ligands was not detectable in the cerebellum of lurcher (Lc/+) mutant mice that lack Purkinje cells, indicating the cells expressing the c-kit ligands were Purkinje cells. The cells expressing c-kit receptors decreased but were present in the cerebellum of Lc/+ mice. The c-kit mRNA-positive cells appeared to represent basket cells and stellate cells from their appearance and location. Since neurons in the molecular layer construct suppressive neurojunctions with Purkinje cells, the present result suggests that c-kit receptors and their ligands may play an important role for the construction of their junctions.

Animals↗

Immunogenetic and nutritional profile in insulin-using youth-onset diabetics in Korea.

There are few reports on the genetic, immunological and nutritional characteristics of insulin-using youth-onset diabetes mellitus, insulin-dependent diabetes mellitus (IDDM) and malnutrition-related diabetes mellitus (MRDM) in Korea. Among 1266 hospitalized Korean diabetics, 29 (2.3%) were IDDM and 84 (6.6%) were MRDM. A diabetes history of first-relatives (28.6%) was more frequently found in the MRDM group than in the IDDM (14.8) and non-insulin-dependent diabetes mellitus (NIDDM) (19.0%) groups. HLA-DR4 was more common among IDDM (54.2%) and MRDM (52.4%) patients than controls (26.3%), and HLA-DR3 was more common among only IDDM patients (29.2%) than controls (10.9%). Conventional islet-cell antibodies were detected in 8 of 15 IDDM patients tested (53.3%) and in 11 of 22 MRDM patients (50.0%). MRDM patients had higher serum basal (1.02 +/- 0.51 ng/ml) and peak (1.44 +/- 0.76 ng/ml) C-peptide concentrations than IDDM patients, but lower concentrations than NIDDM patients. Before the onset of diabetes, the calorie intake of 21 MRDM patients assessed was 63.1% of the daily requirement and the intake of carbohydrate, protein and fat was 71.7%, 55.9% and 39.8%, respectively. In summary, our data suggest that IDDM in Korea is associated with HLA-DR3 or HLA-DR4, indicating a risk for IDDM in Western societies; furthermore, MRDM has a history of undernutrition at the preonset period and is also associated with HLA-DR4. It might be also concluded that MRDM in Korea is another expression of IDDM caused by the shortage of some nutrients for the structural and/or functional maintenance of pancreatic beta-cells.

Adolescent↗

Characterization of Ws mutant allele of rats: a 12-base deletion in tyrosine kinase domain of c-kit gene.

Homozygous mutant rats at the newly found white spotting (Ws) locus were anemic and deficient in mast cells and melanocytes. Because the phenotype of Ws/Ws rats resembled the phenotype of mice possessing a double-gene dose of mutant alleles at the W locus and because the c-kit gene was mapped at the W locus of mice, we characterized the c-kit gene of Ws/Ws rats. The authentic sequence of the rat c-kit cDNA was determined by using a cDNA library prepared from the hippocampus of Sprague-Dawley rats. The c-kit cDNA of Ws/Ws and normal (+/+) control rats was obtained by reverse transcriptase modification of the polymerase chain reaction. When compared with the authentic sequence, a deletion of 12 bases was found in the c-kit cDNA of Ws/Ws rats. This change was shown to be a result of the deletion of the genomic DNA. Four amino acids encoded by the deleted 12 bases (ie, Val-Lys-Gly-Asn) were located at two amino acids downstream from the tyrosine autophosphorylation site in the c-kit kinase and were conserved not only in mouse and human c-kit kinases but also in mouse and human c-fms kinases (ie, receptors of colony-stimulating factor-1). Taken together, the Ws/Ws rat is the first characterized mutant of the c-kit gene in an animal species other than the mouse.

Alleles↗

Facial nerve paralysis associated with Kawasaki disease.

Kawasaki disease is a multisystem disorder with varying clinical expression. This is a report on one case of Kawasaki disease which during its clinical course developed facial nerve palsy and spontaneous recovery without specific treatment. It is hoped that this report will serve to remind physicians of the association of facial nerve paralysis with Kawasaki disease.

Aspirin↗

Coxsackie B virus assays in IDDM families: the GAW5 data on antibody prevalence.

There is evidence that infection by Coxsackie viruses can serve as an environmental "trigger" for insulin-dependent diabetes mellitus (IDDM). This background information is summarized briefly, and the data in the IDDM component of Genetic Analysis Workshop 5 (GAW5) concerning serum antibodies to Coxsackie B viruses are described.

Antibodies, Viral↗

Presence of hexobarbital in primary cultures of rat hepatocytes maintains cytochrome P-450 levels and drug metabolizing enzyme activities.

Addition of hexobarbital (1 mM) to the culture medium of rat hepatocytes protected against the rapid decline in the level of cytochrome P-450 and the activities of various drug metabolizing enzymes. While the hepatocytes cultured for 72 hr without hexobarbital had only 30% of their original level of cytochrome P-450, the cells maintained with hexobarbital had 75% of the initial level of the hemoprotein. After 72 hr in culture, the activities of aminopyrine N-demethylase and biphenyl 4-hydroxylase were 22-24% of the original rate for the nontreated cells and 73-78% for the hexobarbital treated cells. The activities of 7-ethoxycoumarin O-deethylase and aryl hydrocarbon hydroxylase in the cultures of treated cells were even higher than those of the freshly isolated hepatocytes. Additions of other substrates of hepatic mixed function oxidase to the culture medium did not protect against the loss of cytochrome P-450 and enzyme activities.

1-Butanol↗

Immunohistochemical localization of keratin in the taste buds of rat vallate papillae.

Keratin detected with anti-human whole keratin serum, raised in rabbits by injection of the isolated human whole keratin, was used as a histologic marker to study the origin of the cells in taste buds. Rat vallate papillae, including surrounding tissue, were processed for indirect immunofluorescent staining of ketatin. In the taste buds, most basal cells and some of the elongated cells were immunoreactive with anti-keratin serum, showing that most taste-bud cells, if not all, originate from cells of epithelial origin.

Animals↗

Effects of butylated hydroxytoluene (BHT) on biliary excretion of xenobiotics and bile flow in rats.

A significant enhancement in the biliary excretion of iv injected sulfobromophthalein (BSP), phenol- 3,6 -dibromphthalein disulfonate (DBSP), procaine amide ethobromide (PAEB) and ouabain was observed in rats maintained on diets containing 0.25% BHT for periods of 10 days. The enhanced biliary excretion of these drugs in BHT treated rats appears to be correlated with the increase in bile flow produced by BHT. The increased bile flow was due to an increase in canalicular bile production rather than a change in net ductular secretion or reabsorption of fluid since bile to plasma concentration ratios of erythritol were unchanged and no permeability change in the biliary tree was observed when mannitol was administered by retrograde intrabiliary injection. The increase in bile flow was not due to an enhanced excretion of bile salts into bile, because both the biliary bile acid concentration and total biliary excretion of bile acids were lower in BHT-treated rats than in control rats. It appears that the increase in bile flow produced by BHT is due to the osmotic choleresis related to the secretion of BHT and its metabolites into bile.

Animals↗

Non-parametric inference of a failure time distribution when the failure times are estimated.

We consider the estimation of a failure time distribution F when, instead of N i.i.d. realizations T1, T2, ..., TN from F, the observations consist of estimates of the Ti. If the Ti could be observed, a natural non-parametric estimator of F would be the Kaplan-Meier estimator. Thus, we examine the properties of the Kaplan-Meier estimator based on the estimates of the Ti. We also consider a weighted Kaplan-Meier estimator which gives more emphasis to those estimated times based on more information. We evaluate the small sample bias and precision of F when the estimated failure times arise from additive or multiplicative error structures. Because this problem has particular application in the study of non-compliance of subjects in clinical trials, we also investigate the bias and precision of the estimators of the distribution function based on a complex error structure that would arise in the non-compliance setting. Here Ti denotes the unobserved time to non-compliance for the ith subject, and is estimated using repeated observations from a laboratory marker whose behaviour is affected by non-compliance. The techniques are illustrated with the results of a recent AIDS clinical trial.

Acquired Immunodeficiency Syndrome↗

Assessing drug compliance using longitudinal marker data, with application to AIDS.

The assessment of non-compliance to a study medication is an important issue in the evaluation of clinical trials of self-administered drugs. Traditional methods for evaluating the compliance of subjects include self-reported questionnaires and pharmacologic assays of drug levels in randomly-drawn blood samples, but each of these has important limitations. This paper adapts and extends changepoint methods to assess compliance from longitudinal data on laboratory markers that are affected by the drug. The maximum likelihood estimators for two models are developed and examined. The effect of the drug on the marker process, as well as the spacing of the observations of the marker process relative to the time of non-compliance determine which model parameters are estimable. For the situations examined, the method of maximum likelihood is found to perform well in most cases. However, when non-compliance begins shortly before the last observation of the marker process, these (as well as any other) estimators cannot reliably distinguish non-compliance from compliance. The methods are illustrated with an example from a recent clinical trial of persons infected with HIV.

Acquired Immunodeficiency Syndrome↗

T-cell specific immunosuppression by prodigiosin isolated from Serratia marcescens.

Prodigiosin was isolated from the culture broth of Serratia marcescens B-1231. This compound inhibited the T-cell mediated immune responses such as concanavalin-A induced proliferation, mixed lymphocyte response, local graft vs host reaction and T-dependent antibody response at non-toxic concentrations. However, prodigiosin did not affect B-cell mediated immune functions such as lipopolysaccharide-induced proliferation and-activated polyclonal antibody production at the same concentrations. Prodigiosin did not cause death in vitro to lymphocytes at effective concentrations (< 100 nM) and also did not show toxicity in vivo to lymphoid organs at effective dosages (10 and 30 mg/kg). The pharmacological potencies were comparable to the activities of other T-cell specific immunosuppressants such as cyclosporin A and FK-506. In conclusion, it might be suggested that prodigiosin could be used as an immunosuppressant in clinical and immunological studies.

Animals↗