Biomedical subjects

D J Kim

Publications and source records attributed to D J Kim.

At least 145 records · Page 8Linked to original sources

PubMed1997

Molecular epidemiological analysis of quinolone-resistant Escherichia coli causing bacteremia in neutropenic patients with leukemia in Korea.

We analyzed an outbreak of Escherichia coli bacteremia in eight patients with leukemia in a hematology-oncology unit from July to September 1994. The antibiograms and genotypic patterns of the isolates were different, thus suggesting that the outbreak did not originate from a single clone. However, all the isolates were resistant to quinolones, which led us to examine the microbiological records from 1992 to 1994. The incidence of quinolone-resistant E. coli bacteremia in the hematology-oncology unit ranged from 81.8% to 94.6% during this period. We then analyzed 36 more isolates recovered from late 1994 to 1995. Field inversion gel electrophoresis patterns of these isolates were also different. Analysis of the quinolone resistance determining region in gyrA revealed that all the isolates had a double mutation in gyrA. In conclusion, quinolone-resistant E. coli could be an emerging threat to neutropenic patients with leukemia who receive a quinolone prophylactically, and attention must be paid to this trend of resistance.

4-Quinolones↗

PubMed1997

Enhancement by indole-3-carbinol of liver and thyroid gland neoplastic development in a rat medium-term multiorgan carcinogenesis model.

The modification potential of indole-3-carbinol (I3C), a naturally occurring compound found in cruciferous vegetables, on neoplastic development was assessed using a rat medium-term multiorgan carcinogenesis model. One-hundred male Sprague-Dawley (SD) rats were randomly divided into three groups and sequentially treated with diethylnitrosamine (DEN; 100 mg/kg b.w., a single i.p.), N-methyl-N-nitrosourea (MNU; 20 mg/kg b.w., four times i.p., at days 5, 8, 11 and 14), and dihydroxy-di-N-propyl-nitrosamine (DHPN; 0.1% in the drinking water during weeks 1 and 3) (DMD treatment; groups 1 and 2) or the vehicles alone (group 3) in the first 3-week initiation period. Animals of groups 1 and 3 were then given diet containing 0.25% I3C from week 4 until week 24, followed by a return to basal diet for 28 weeks, and subgroups were killed at weeks 24 and 52. I3C caused significant increases in both number (no./cm2) and area (mm2/cm2) of glutathione S-transferase placental form (GST-P)-positive liver cell foci assessed at week 24 of the experiment (P<0.01, 0.001). The incidence of hepatocellular adenomas in the DMD and I3C group at week 52 showed a tendency for elevation as compared to the DMD alone group, but this was not statistically significant. The thyroid gland tumour incidences in the DMD and I3C groups were significantly increased compared with the DMD alone group values at week 52 (P<0.01). In conclusion, I3C enhanced liver and thyroid gland neoplastic development when given during the promotion stage in the present rat medium-term multiorgan carcinogenesis model.

Adenocarcinoma↗

PubMed1997

Demonstration of ras and p53 gene mutations in carcinomas in the forestomach and intestine and soft tissue sarcomas induced by N-methyl-N-nitrosourea in the rat.

The presence of ras family and p53 gene mutations in rat forestomach, intestine and liver tumors and soft tissue sarcomas induced by N-methyl-N-nitrosourea (MNU) was examined using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) followed by direct sequencing analysis. In the forestomach squamous cell carcinomas (SCC), Ha-ras and p53 mutations were detected in 2 (40%) and 4 (80%) of 5 cases, respectively. The figures for Ki-ras and p53 gene mutations in adenocarcinomas of the large and small intestines were 3 (18.8%) and 5 (31.3%) of 16 cases. Soft tissue sarcomas in different sites were found to have mutations of Ki-ras in 7 (23.3%) and of p53 in 9 (30%) of 30 cases. One forestomach SCC and 2 soft tissue sarcomas had double p53 mutations in different exons. Single cases of forestomach SCC and intestinal adenocarcinoma had mutations in both Ki-ras and p53 genes. No mutations were found in counterpart benign tumors or hepatocellular adenomas. The p53 mutation spectrum revealed preferential clustering within exon 8 for the forestomach SCCs, and exons 5 and 8 for the intestinal adenocarcinomas, whereas the distribution was evenly spread through exons 5 to 8 in soft tissue sarcomas. All the detected ras or p53 mutations were G:C to A:T transitions. These results indicate firstly that specific Ki-ras, Ha-ras and p53 gene mutations in MNU-induced lesions are related to particular alkylation sites (G:C to A:T transitions) and secondly, although not essential, Ki-ras, Ha-ras or p53 gene mutations may be involved in the progression stage of forestomach, intestine and soft tissue neoplasms induced by MNU.

Adenocarcinoma↗

PubMed1997

Inhibition of azoxymethane-initiated colon tumor by bovine lactoferrin administration in F344 rats.

The influence of bovine lactoferrin (bLF) on colon carcinogenesis was investigated in male F344 rats treated with azoxymethane (AOM). Following three weekly injections of AOM, the animals received 2 or 0.2% bLF for 36 weeks. No effects indicative of toxicity were noted, but significant reduction in both the incidence and number of adenocarcinomas of the large intestine was observed with both doses. Thus, the incidences of adenocarcinomas in the groups receiving 2% and 0.2% bLF were 15% and 25%, respectively, in contrast to the 57.5% control value (P < 0.01 and P < 0.05, respectively). The results indicate that bLF might find application for chemoprevention of colon cancer.

Adenocarcinoma↗

PubMed1997

Helicobacter pylori infection and the risk of gastric cancer among the Korean population.

Helicobacter pylori infection has been associated with chronic atrophic gastritis, a precursor of gastric cancer. We conducted a prospective, case-controlled study to investigate whether H. pylori infection increases the risk of gastric cancer in Korean people with a high risk of gastric cancer. We enrolled 160 gastric cancer patients who were confirmed by endoscopic biopsy during 1994 and 160 age-matched control subjects with non-ulcer dyspepsia were compared to document the relationship between H. pylori infection and gastric cancer. The presence of H. pylori infection was determined by the rapid urease test and/or histology by Wright-Giemsa staining. The overall presence of H. pylori infection was 60% in gastric cancer patients and 51.9% in age-matched control subjects (odds ratio 1.39; 95% confidence interval 0.894-2.17; P = 0.143). Carcinomas of cardia, body and antrum were not associated with H. pylori infection (odds ratio 1.43, 1.69 and 1.29, respectively; 95% confidence interval, 0.271-7.52, 0.787-3.62 and 0.689-2.43, respectively; P = 0.178, 0.177 and 0.642, respectively) nor was the intestinal or diffuse type of cancer (odds ratio 1.39 and 1.40, respectively; 95% confidence interval 0.791-2.45 and 0.681-2.87, respectively; P = 0.250 and 0.835, respectively). Gender was not a risk for gastric cancer. In contrast to previous studies, these results do not provide evidence of H. pylori infection for gastric carcinogenesis in Korea.

Adenocarcinoma↗

PubMed1997

Isolation and characterization of mouse coagulation factor X -- biophysical and enzymological properties.

Mouse factor X was highly purified from plasma using barium ion precipitation and chromatography on anion-exchange and heparin-agarose affinity chromatography columns. Intact and reduced patterns of mouse factor X in SDS-PAGE were similar to those of human factor X. The specific absorption E 1%/1 cm at 280 nm of mouse factor X was found to be 11.2. Content of carbohydrate moieties of mouse factor X, determined to be 10% by weight, differs both quantitatively and quantitatively from that of human factor X, while the gamma-carboxyglutamic acid (Gla) and beta-hydroxy-aspartic acid (beta-OH-Asp) content were essentially the same as for human factor X. The amino-terminal amino acid sequences of the light and heavy chains of mouse factor X separated by SDS-PAGE were ANSFF--FKK and SVALXTSDSE, respectively. Underlined residues are non-identical with those of human factor X. Clotting time-based assays using human factor X-deficient plasma as substrate exhibited the following apparent extents of activation of factor X in mouse plasma, using human plasma as the standard: 195% (intrinsic); 200% (extrinsic); and 190% (RVV-X). Using the purified proteins in the same assay systems, the following apparent activation of mouse factor X was demonstrated, compared with human factorX: 195% (intrinsic); 27% (extrinsic); and 41% (RVV-X). These activity profiles suggest that the human extrinsic coagulation pathway functions less efficiently than the corresponding mouse pathway in the activation of mouse factor X. Furthermore, mouse brain thromboplastin satisfactorily replaced rabbit brain thromboplastin in extrinsic activation of factor X in mouse plasma, but not of human plasma or purified mouse or human factor X, in line with studies by others suggesting that human factor VIIa poorly activates factor X in the presence of mouse tissue factor. While fully RVV-X-activated mouse factor X activated human prothrombin at a rate equal to about 117% of that for human factor X, it hydrolyzed the synthetic substrate, S-2222, at a rate of only about 18% of that for human factor X. These results are expected to be useful in making the mouse suitable for study of the mammalian blood coagulation pathways.

Amino Acids↗

PubMed1996

Promotion potential of tamoxifen on hepatocarcinogenesis in female SD or F344 rats initiated with diethylnitrosamine.

The liver promotion potential of tamoxifen (TAM), which has been widely used in the treatment of hormone-dependent breast cancers, was investigated using female SD or F344 rat initiated with diethylnitrosamine (DEN). In Experiment 1, 45 newborn female SD rats were administered DEN (100 mg/kg, i.p.) (Groups 1 and 2) or saline (Group 3) 24 h after birth. After weaning at week 3, Groups 1 and 3 were subcutaneously injected with TAM citrate (1 mg/rat per day), suspended in corn oil, in the subscapular region, while Group 2 was given the vehicle alone (s.c.) daily for 9 weeks, and killed at week 12. In Experiment 2, 70 female F344 rats at 7 weeks of age were divided into five groups. All animals were initially given DEN (200 mg/kg i.p.) for initiation. Two weeks later Groups 1-4 were given diets containing 100, 250, 500 ppm TAM, or 500 ppm PB for 6 weeks, respectively, while Group 5 was administered basal diet as a control for the same period. The rats were subjected to two-thirds partial hepatectomy (PH) at week 3 and were killed at week 8. The enhanced development of glutathione S-transferase-placental form (GST-P)-positive liver cell foci after DEN exposure in both newborn SD and adult F344 rat medium-term liver bioassay models (Experiments 1 and 2). This suggests that TAM exerts promotion potential for hepatocarcinogenesis in female rats.

Animals↗

PubMed1996

Nicotine cue: lack of effect of the alpha 7 nicotinic receptor antagonist methyllycaconitine.

To assess the role of the alpha 7 neuronal nicotinic acetylcholine receptor in the discriminative stimulus properties of (-)-nicotine, this study investigated the ability of the alpha 7 receptor antagonist methyllycaconitine to modulate the nicotine cue. In rats trained to discriminate (-)-nicotine from saline, intraperitoneal injections of methyllycaconitine neither induced nor blocked the nicotine cue. Intracerebroventricular administration of methyllycaconitine, neither potentiated nor blocked the effect of (-)-nicotine. On the other hand, intracerebroventricular injections of mecamylamine blocked the nicotine cue. The available evidence indicate that the nicotinic acetylcholine receptors in the brain blocked by methyllycaconitine, those presumably containing alpha 7 subunits, do not participate in the expression of the discriminative stimulus properties of (-)-nicotine.

Aconitine↗

PubMed1996

c-Jun activation of the DYNCRE3 site in the prodynorphin promoter.

The DYNCRE3 site in the prodynorphin promoter is similar to both the AP-1 and cAMP-responsive element (CRE) consensus sequences. Because c-Jun is known to bind to both AP-1 and CRE sequences, we evaluated the potential role of this transcription factor at the DYNCRE3 site using transient transfection and gel mobility shift analyses. In PC12 cells, co-transfections of a chloramphenicol acetyl transferase (CAT) reporter gene containing the DYNCRE3 site and a c-Jun expression vector resulted in transcriptional activity 9-fold greater than control. Co-transfections with a mutant c-Jun protein lacking the transactivation domain resulted in a concentration-dependent decrease in transcriptional activity. Gel mobility shift analysis demonstrated the formation of a multi-component protein-DNA complex between an oligonucleotide centered on the DYNCRE3 site and nuclear extract from untreated and forskolin-stimulated PC12 cells. The upper band of this complex could be completely supershifted with the addition of a c-Jun specific antibody. These convergent data suggest that c-Jun is involved in transcriptional activation through the DYNCRE3 site.

Animals↗

PubMed1996

Systemic lupus erythematosus with nephritis is strongly associated with the TNFB*2 homozygote in the Korean population.

To evaluate the association of TNFB NcoI polymorphism with SLE in the Korean population, we investigated the frequencies of the TNFB and HLADRB1 alleles in 281 controls and 97 SLE patients, including 56 patients with nephritis and 41 patients without nephritis. The frequency of the TNFB*2 homozygote in SLE was significantly increased over controls (43.3% vs 28.5%, RR = 1.9,p < 0.01). In SLE with nephritis, the TNFB*2 homozygote was more significantly increased (57.1% vs 28.5%, RR = 3.4,p < 0.0001), whereas there was no significant difference between SLE without nephritis and controls. The study of HLA-DRB 1 alleles revealed the increased frequencies of DRB1*02 and *03 (30.9% vs 18.2%, RR = 2.0,p < 0.01; 8.2% vs 2.1%, RR = 4.1,p < 0.05). There was no significantly different distribution of HLA-DRB1 alleles between SLE patients with nephritis and without nephritis. We found positive LD between TNFB*1 and HLA-DR1B1*13, and between TNFB*2 and the particular DRB1 allele: *15, *04, and *07 in controls and/or in SLE patients. After stratification for each HLADRB1 allele, SLE with nephritis showed a higher frequency of TNFB*2 homozygote compared with the corresponding controls in DRB1*15, *08, and *09 positives. Our results suggest that the TNFB*2 homozygote may be a strong susceptibility gene of SLE with nephritis in the Korean population.

Alleles↗

PubMed1996

A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex. The Multiple Sclerosis Genetics Group.

Multiple sclerosis (MS), an inflammatory autoimmune demyelinating disorder of the central nervous system, is the most common cause of acquired neurological dysfunction arising in the second to fourth decades of life. A genetic component to MS is indicated by an increased relative risk of 20-40 to siblings compared to the general population (lambda s), and an increased concordance rate in monozygotic compared to dizygotic twins. Association and/or linkage studies to candidate genes have produced many reports of significant genetic effects including those for the major histocompatability complex (MHC; particularly the HLA-DR2 allele), immunoglobulin heavy chain (IgH), T-cell receptor (TCR) and myelin basic protein (MBP) loci. With the exception of the MHC, however, these results have been difficult to replicate and/or apply beyond isolated populations. We have therefore conducted a two-stage, multi-analytical genomic screen to identify genomic regions potentially harbouring MS susceptibility genes. We genotyped 443 markers and 19 such regions were identified. These included the MHC region on 6p, the only region with a consistently reported genetic effect. However, no single locus generated overwhelming evidence of linkage. Our results suggest that a multifactorial aetiology, including both environmental and multiple genetic factors of moderate effect, is more likely than an aetiology consisting of simple mendelian disease gene(s).

Chromosome Mapping↗

PubMed1996

Determining the maximal length of a vein conduit used as an interposition graft for nerve regeneration.

Although autogenous veins have been used as nerve conduits (AVNCs) both experimentally and clinically for short nerve gaps up to 3 cm, investigators have not as yet determined the maximal effective length for functional nerve regeneration. In addition, the role of the distal nerve stump on subsequent nerve growth remains unclear. A rabbit peroneal nerve AVNC model was used to study axonal regeneration through nerve gaps of 1 to 6 cm. After allowing ample time for nerve regeneration, clinical, electophysiologic and neurohistologic studies were performed to evaluate nerve growth and functional muscle reinnervation. Comparisons were made with 6-cm conventional nerve grafts. Excellent growth and function were found with AVNCs up to 3 cm in length, with increasing incapacity for regeneration at lengths greater than 3 cm. The distal nerve stump is believed to play a vital role in nerve regrowth.

Animals↗

PubMed1996

Decreased connexin32 and a characteristic enzyme phenotype in clofibrate-induced preneoplastic lesions not shared with spontaneously occurring lesions in the rat liver.

Two different types of focal preneoplastic lesions, tentatively named Type I and II lesions, were recognized in the liver of rats chronically treated with clofibrate for 104 weeks. Type I lesions were characterized by mostly negative glucose-6-phosphate dehydrogenase (G6PD) activity (6 out of 10, 60%) and positive expression of succinate dehydrogenase (10 out of 10, 100%), in addition to the previously documented complete lack of expression of glutathione S-transferase, placental form (GST-P) and gamma-glutamyl transpeptidase (GGT). Furthermore, most importantly, Type I lesions exhibited a clear decrease in immunohistochemically demonstrated connexin32 (Cx32) spot counts on their hepatocyte membranes, similarly to nitrosamine-induced lesions. In contrast, Type II lesions, mostly small in size and positively expressing GST-P and/or GGT and G6PD, similarly to their previously reported nitrosamine-induced counterparts, did not exhibit a significant decrease in Cx32 count. In addition, spontaneously occurring lesions, again sharing the same enzyme phenotype, did not show a decrease in Cx32. The results indicate that: (i) a clear distinction between the two lesions, with Type I being involved in clofibrate-induced tumors and Type II being more likely to be spontaneous in nature; (ii) a decrease in Cx32 is closely linked to lesion development and possibly stage of progression, irrespective of the enzyme phenotype and the applied carcinogen; (iii) the unaltered condition of Cx32 may suggest a slow growing or non-progressive nature.

Animals↗

PubMed1996

Neuromodulation of transduction and signal processing in the end organs of taste.

Chemical synapses transmit gustatory signals from taste receptor cells to sensory afferent axons. Chemical (and electrical) synapses also provide a lateral pathway for cells within the taste bud to communicate. Lateral synaptic pathways may represent some form of signal processing in the peripheral end organs of taste. Efferent synaptic input may also regulate sensory transduction in taste buds. To date, the synaptic neurotransmitter(s) or neuromodulator(s) released at chemical synapses in taste buds have not been identified unambiguously. This paper summarizes the attempts that have been made over the past 40 years to identify the neuroactive substances acting at taste bud synapses. We review the four traditional criteria for identifying chemical transmitters elsewhere in the nervous system-localization, uptake/degradation, release and physiological actions- and apply these criteria to neuroactive substances in taste buds. The most complete evidence to date implicates serotonin as a neuromodulator of taste transduction in the end organs. However, studies also suggest that adrenergic, cholinergic and peptidergic neurotransmission may be involved in taste buds.

Animals↗

PubMed1996

Modifying influence of swine-serum-induced liver fibrosis on development of preneoplastic lesions in rat liver.

Modifying effects of fibrosis or a cirrhotic state, caused by treatment with swine serum (SS), on the induction of preneoplastic focal lesions were assessed in a rat medium-term liver bioassay model for the detection of environmental carcinogens, in which the test compound is administered during the promotion phase after initiation with diethylnitrosamine. In experiment I, repeated intraperitoneal administration of SS concomitantly with the hepatopromoting agent deoxycholic acid (DCA) or phenobarbital (PB) resulted in a cirrhotic state and a significant increase in the number or size of preneoplastic glutathione S-transferase placental form (GST-P)-positive liver cell foci as compared to the corresponding DCA or PB alone groups. In experiment II, SS was given prior to commencement of the same medium-term bioassay system, in which a known hepatopromoting agent, DCA, 17-alpha-ethynylestradiol, or 2-acetylaminofluorene, was applied. In this case, the liver did not show obvious cirrhotic change and, rather than any enhancement, slight inhibition of promotion occurred. The results indicate that a coexisting, but not a pre-existing, cirrhotic condition acts to increase growth pressure on GST-P+ preneoplastic foci, and suggest that concomitant administration of SS with the promoting agent could be applied to improve the sensitivity of the assay protocol.

2-Acetylaminofluorene↗

PubMed1996

Membrane properties and cell ultrastructure of taste receptor cells in Necturus lingual slices.

1. Whole cell patch-clamp recordings and electron micrographs were obtained from cells in Necturus taste buds in lingual slices to study their membrane properties and to correlate these properties with cell ultrastructure. 2. Two different populations of taste receptor cells could be identified: one type possessed voltage-gated Na+ and K+ (noninactivating) currents (group 1 cells); the other type possessed only K+ (inactivating) currents (group 2 cells). 3. The zero-current ("resting") potential (Vo) and whole cell resistance (Ro) of these two types of taste cells differed significantly. For group 1 cells, on average, Vo = -75 mV and Ro = 24.6 G omega, and for group 2 cells, Vo = -49 mV and Ro = 48.9 G omega. The difference in Ro was not explained completely by differences in cell sizes, suggesting that intrinsic membrane properties differed between the populations. 4. Cells injected with biocytin were the electron microscope after tissues were reacted with majority (14 of 16) of cells with voltage-gated Na+ and K+ currents (group 1 cells) were characterized by abundant rough endoplasmic reticulum and dense granular packets in the apical process. These are features of dark cells. All the cells that only possessed K+ currents (group 2 cells) were characterize by well-developed smooth endoplasmic reticulum and an absence granular packets. These features characterize light cells. 5. These findings indicate that there is a good, although not exact, correlation between electrophysiological properties and cell morphotype in Necturus taste bud cells. All dark cells possessed Na+ and K+ currents and thus would be expected to be capable of generating action potentials. Most light cells only possessed outward K+ currents and thus would be incapable of generating action potentials.

Animals↗

PubMed1996

Posterior pedicular screw instrumentation and anterior interbody fusion in adult lumbar spondylolysis or grade I spondylolisthesis with segmental instability.

Between 1988 and 1993, we treated 21 adults with symptomatic lumbar spondylolysis by a combined surgery of posterior stabilization and anterior interbody fusion. Our indication for this combined surgery was persistent pain that was unresponsive to conservative measures and segmental instability on flexion-extension roentgenogram. The patients' mean age at the time of surgery was 34 years (range 24-42 years). All patients showed degenerated disks on preoperative magnetic resonance imaging. The mean follow-up period was 30.4 months. The clinical result was excellent or good in 95%, and the radiographic fusion was successful in 95%. Prolonged pain at the donor site was the most common complication, which usually disappeared by 3 months after the operation. We recommend the combined surgery of posterior instrumentation and anterior fusion to stabilize symptomatic adult lumbar spondylolysis.

Adult↗

PubMed1996

Characterization of recombinant human coagulation factor XFriuli.

Naturally occurring plasma factor XFriuli (pFXFr) is marginally activated by both the extrinsic and intrinsic coagulation pathways and has impaired catalytic potential. These studies were initiated to obtain confirmation that this molecule is multi-functionally defective due to the substitution of Ser for Pro at position 343 in the catalytic domain. By the Nelson-Long site-directed mutagenesis procedure a construct of cDNA in pRc/CMV was derived for recombinant factor XFriuli (rFXFr) produced in human embryonic (293) kidney cells. The rFXFr was purified and shown to have a molecular size identical to that of normal plasma factor X (pFX) by gel electrophoretic, and amino-terminal sequencing revealed normal processing cleavages. Using recombinant normal plasma factor X (rFXN) as a reference, the post-translational gamma-carboxy-glutamic acid (Gla) and beta-hydroxy aspartic acid (beta-OH-Asp) content of rFXFr was over 85% and close to 100%, respectively, of expected levels. The specific activities of rFXFr in activation and catalytic assays were the same as those of pFXFr. Molecular modeling suggested the involvement of a new H-bond between the side-chains of Ser-343 and Thr-318 as they occur in anti-parallel beta-pleated sheets near the substrate-binding pocket of pFXFr. These results support the conclusion that the observed mutation in pFXFr is responsible for its dysfunctional activation and catalytic potentials, and that it accounts for the moderate bleeding tendency in the homozygous individuals who possess this variant procoagulant.

1-Carboxyglutamic Acid↗