Biomedical subjects

D J Kim

Publications and source records attributed to D J Kim.

At least 127 records · Page 7Linked to original sources

PubMed1998

Cytotoxic effects of quinoxaline derivatives on human cancer cell lines.

The cytotoxicities of 6,7-modified-5,8-quinoxalinedione derivatives and heterocyclic quinoxaline derivatives containing nitrogen, sulfur, and oxygen on human lung adenocarcinoma cell (PC 14), human gastric adenocarcinoma cell (MKN 45), and human colon adenocarcinoma cell (colon 205) were examined in vitro using MTT assay. Pyrido[1,2-a]imidazo[4,5-g]quinoxaline-6,11-dione (10) was markedly cytotoxic against MKN 45 compared with adriamycin and cis-platin used as anticancer drugs. The IC50 value of compound 10 was 0.073 microM while those of adriamycin and cis-platin were 0.12 microM and 2.67 microM, respectively.

Antineoplastic Agents↗

PubMed1998

Inhibition of azoxymethane initiated colon tumor and aberrant crypt foci development 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). In experiment I, 2% and 0.2% bLf, and Bifidobacterium longum (B. longum) as a positive control at 3% were given in the diet for 4 weeks, along with two s.c. 15 mg/kg injections of AOM on days 1 and 8. The numbers of aberrant crypt foci (ACF) were decreased by both treatments. Similar results were obtained in experiment II of 13 weeks duration. In experiment III, animals were given three weekly injections of AOM and then received 2 or 0.2% bLf, 2% bLf-hydrolysate, or 0.1% bovine lactoferricin (bLfcin) 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 almost all the treatments. Thus, the incidences of colon adenocarcinomas in the groups receiving 2 or 0.2% bLf, 2% bLf-hydrolysate, or 0.1% bLfcin were 15%, 25%, 26.3% and only 10%, respectively, in contrast to the 57.5% control value (p < 0.01). ACF values also exhibited reduced development. Investigation of beta-glucuronidase revealed decrease in the cecal contents of animals receiving bLf. In addition, demonstration of enhancement of NK activity by bLf indicated that its inhibitory effects could have been related to elevated immune cytotoxicity.

Animals↗

PubMed1998

Differential effects of nongenotoxic and genotoxic carcinogens on the preneoplastic lesions in the rat liver.

Glutathione S-transferase placental form (GST-P) positive foci development and its expression in liver exposed by nongenotoxic carcinogens phenobarbital (PB) and clofibrate (CF), and genotoxic carcinogen 2-amino-3-methylimidazo[4,5-f] quinoline (IQ) were investigated as a measure of carcinogenic potential of these chemicals. Male F344 rats were initially given a single intraperitioneal injection of diethylnitrosamine (200 mg/kg), and 2 weeks later, animals were fed diets containing 0.03% IQ or 0.5% CF or 0.05% PB or basal diet as a control for 6 weeks. All rats were subjected to two-thirds partial hepatectomy (PH) at week 3. Sequential sacrifice of rats was performed at 8 weeks or 52 weeks, and liver tissues were examined for immunohistochemical staining of GST-P positive foci. The numbers (No./cm2) and areas (mm2/cm2) of GST-P positive foci were increased by IQ or PB, but were decreased by CF compare to the control. Consistent with the development of GST-P positive foci, a time-related increase in the expression of GST-P mRNA was found in the rats treated with IQ, whereas CF decreased it. The incidence of hepatocellular carcinoma at 52 weeks was increased by all three chemicals. These results show that PB and IQ induced GST-P positive foci, but the peroxisome proliferator CF did not, which suggest that the prediction of carcinogenic potency based on the development of prenoplastic foci may cause false negative in a particular category compounds like peroxisome proliferators.

Administration, Oral↗

PubMed1998

Transcription factor regulation of prodynorphin gene expression following rat hindpaw inflammation.

Both c-Fos and prodynorphin mRNA and peptide increase unilaterally in nociceptive-specific neurons in the lumbar rat spinal cord during chronic hindpaw inflammation. To study the mechanisms underlying prodynorphin gene expression, we examined transcription factors and their interactions at the CRE/AP-1-like site, DYNCRE3, found in the prodynorphin gene promoter. CREB repressed while c-Fos and c-Jun activated transcription through the DYNCRE3 site in transient co-transfections in PC12 cells. Following inflammation of the rat hindpaw, immunostaining demonstrated a bilateral increase in phosphorylated CREB (P-CREB)-positive neurons in the spinal cord. Gel supershift studies showed that spinal cord extracts contained CREB, P-CREB, and phosphorylated c-Jun (P-c-Jun) proteins that bound to the DYNCRE3 site. We propose a model in which inflammation-induced phosphorylation of CREB relieves CREB repression at the DYNCRE3 site, P-CREB binds to the c-Fos promoter, and Fos/Fra, P-CREB, and P-c-Jun interact at the DYNCRE3 site to activate prodynorphin gene transcription.

Animals↗

PubMed1998

An anatomical study of the junction of the orbital septum and the levator aponeurosis in Orientals.

The anatomical relationships of the orbital septum and levator aponeurosis has been studied in 40 eyelids subjected to blepharoplasty and corrective ptosis surgery by dissection in 10 cadavers and in histological sections. The orbital septum originates from the arcus marginalis of the frontal bone and consists of two layers. The whitish outer (superficial) layer, containing vertically running vessels, descends just inside the orbicularis oculi muscle to interdigitate with the levator aponeurosis with loose connective tissue, then disperses inferiorly. The inner (deep) layer follows the superficial one initially, then reflects at the levator aponeurosis and continues posteriorly with the levator sheath. We reconfirmed Whitnall's original description that the levator sheath thickens to form the superior transverse ligament runs continuously inferiorly anterior to the levator aponeurosis and forms the inner layer of the orbital septum. This detailed anatomical analysis should assist in performing upper eyelid surgery such as the Oriental double fold operation or levator resection.

Asian People↗

PubMed1998

Chemopreventive effects of carotenoids and curcumins on mouse colon carcinogenesis after 1,2-dimethylhydrazine initiation.

The present study was carried out to examine the chemopreventive effects of carotenoids such as fucoxanthin, lycopene and lutein as well as curcumin and its derivative, tetrahydrocurcumin (THC), on development of putative preneoplastic aberrant crypt foci (ACF) in colons of mice initiated with 1,2-dimethylhydrazine dihydrochloride (DMH). Influence on proliferation of colonic crypt epithelial cells was also assessed in terms of 5-bromo-2'-deoxyuridine (BrdU) incorporation. Five-week-old B6C3F1 male mice were divided into three groups, groups 1 and 2 being given DMH (20 mg/kg body wt, s.c.) twice a week for 3 weeks. Animals of group 1 were then treated with one of the test compounds, lycopene (0.005% and 0.0025%) or fucoxanthin (0.01%) in the drinking water and lutein (0.05%), curcumin (0.5%) or THC (0.5% and 0.2%) in the diet from weeks 5-12. Group 2 served as a carcinogen alone control and group 3 mice were given test compounds alone. All animals were killed at week 12. Numbers of ACF/mouse in the group 1 treated with fucoxanthin (47.1 +/- 13.7), lutein (42.6 +/- 19.6) or 0.5% THC (46.6 +/- 17.7) were significantly decreased as compared to the control group 2 value (63.3 +/- 19.4) (P < 0.01). Numbers of aberrant crypts (ACs)/mouse were also significantly lower after treatment with lutein (79.9 +/- 34.7) or 0.5% THC (81.8 +/- 32.5) than in the control group (115.1 +/- 37.1) (P < 0.01). BrdU labeling indices (LI) in mice treated with lutein and 0.5% THC were significantly decreased in both upper and lower half compartments of colonic crypts as compared to the controls (P < 0.05 and 0.01, respectively), especially the upper half data corresponding to reduction of ACs/mouse. The results thus suggest that fucoxanthin, lutein, and THC may have potential as chemopreventive agents against colon carcinogenesis.

1,2-Dimethylhydrazine↗

PubMed1998

TNF-alpha inhibits liver collagen-alpha 1(I) gene expression through a tissue-specific regulatory region.

Although tumor necrosis factor-alpha (TNF-alpha) inhibits collagen-alpha 1(I) gene expression in cultured hepatic stellate cells, assessment of its effects on hepatic collagen expression is complicated by the confounding variables of tissue necrosis and inflammation. Therefore, we analyzed whether chronically elevated serum TNF-alpha affects constitutive hepatic collagen metabolism in vivo by inoculating nude mice with Chinese hamster ovary (CHO) cells secreting TNF-alpha (TNF-alpha mice) or with control CHO cells (control mice). Before the onset of weight loss, collagen synthesis and collagen gene expression were inhibited in the liver of TNF-alpha mice. In transgenic mice, after 8 h, TNF-alpha (500 ng at 0 and 5 h) inhibited the liver expression of the collagen-alpha 1(I)-human growth hormone (hGH) transgene containing the first intron and -440 bp of the 5' region. Similarly, in cultured hepatic stellate cells isolated from these transgenic animals, the -440 bp collagen-alpha 1(I)-hGH transgene was responsive to TNF-alpha treatment independent of the activation of these cells. Transfection studies in stellate cells allowed further characterization of this TNF-alpha-responsive segment to -220 bp of the 5' region. Because in the skin the inhibitory effect of TNF-alpha involves a regulatory region of the collagen-alpha 1(I) gene beyond -440 bp, we herein identify a novel tissue-specific regulation of collagen-alpha 1(I) gene by TNF-alpha.

Animals↗

PubMed1998

Neurotoxicity mediated by aberrant patterns of synaptic activity between rat hippocampal neurons in culture.

Reducing the extracellular Mg2+ concentration ([Mg2+]o) to 0.1 mM evoked an aberrant pattern of glutamatergic activity in the synaptic network formed by rat hippocampal neurons grown in primary culture. This treatment resulted in a significant increase in neuronal death when maintained for 20-24 h; 0.1 mM [Mg2+]o elicited a stable and repetitive series of intracellular Ca2+ concentration ([Ca2+]i) spikes as indicated by indo-1-based microfluorimetry. Fura-2-based digital imaging experiments found that the [Ca2+]i spikes were synchronized for all the neurons in a given field. Thus electrophysiological recordings from individual cells were reasonable representations of the field as a whole, enabling correlation of electrical activity to viability. Underlying each [Ca2+]i spike was an intense burst of action potentials. Whole cell voltage-clamp experiments showed that a burst was composed of fast action currents superimposed on a slow inward current. The N-methyl--aspartate (NMDA) receptor antagonist CGS19755 (10 microM) blocked [Ca2+]i spiking, the slow inward current, and the cell death induced by low [Mg2+]o. The L-type Ca2+ channel antagonist nimodipine (10 microM) blocked [Ca2+]i spiking, all synaptic activity, and the cell death induced by low [Mg2+]o. The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) exerted variable effects on [Ca2+]i spiking and blocked the slow inward current only when the cells were held at a relatively negative holding potential. CNQX did not afford any protection from 0.1 mM [Mg2+]o-induced neurotoxicity. [Ca2+]i imaging experiments showed that CNQX inhibited [Ca2+]i spiking in a subset of neurons within an active network. Thus, the neurons that were insensitive to CNQX appear to be those that were destined to die. We characterized an in vitro model that allowed us to correlate specific electrophysiological components of glutamatergic synaptic activity to the subsequent viability of the network. A slow NMDA receptor-mediated inward current was required to elicit [Ca2+]i spiking and neurotoxicity. Non-NMDA receptors did not contribute to synaptically mediated cell death in this model. An L-type Ca2+ channel antagonist was neuroprotective when used at concentrations that blocked synaptic activity, suggesting that dendritic L-type Ca2+ channels present a useful target for neuroprotective drugs.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1998

A new method of stabilising the elevated laminae in open-door laminoplasty using an anchor system.

We treated 12 patients with multilevel stenosis of the cervical canal after spondylosis or ossification of the posterior longitudinal ligament by an expansive open-door laminoplasty, stabilised by using an anchor system. The preoperative sagittal diameter of the canal was 9.8 mm(+/-2.2) which was increased to 16.1 mm(+/-2.9) after surgery. The mean expansion ratio of the canal was 64% (42 to 100). The anchoring systems did not fail during the follow-up period (mean 29.5 months), and the decompression was maintained. The use of anchor systems to stabilise the posterior elements after laminoplasty is a simple and effective technique for maintaining the increased sagittal diameter of the canal.

Aged↗

PubMed1998

Evidence of protein kinase C translocation by ischemic preconditioning in global ischemia model.

We tested recent evidence that ischemic preconditioning (PC) involves in translocation of protein kinase C (PKC) from the cytosol to myocyte membrane. Isolated Langendorff-perfused rabbit hearts (n=96) were subjected to 60 or 45 min of ischemia (I) and 120 min of reperfusion (R) with or without PC (4 cycles of 5 min I and 5 min R; or single dose of 5 min I and 10 min R), respectively. Left ventricular function and infarct size (IS) were measured; myocardial cytosolic and membrane PKC activity were determined by 32P-gamma-ATP incorporation into PKC-specific peptide. PC enhanced improvement of functional recovery and reduced IS (26.9+/-1.4% versus 15.3+/-1.9%, p<0.01, in 60 min of I; 18.3+/-2.6% versus 8.6+/-2.5%, p<0.05, in 45 min of I); cytosolic PKC activity decreased 74% of total activity (p<0.05) both in 60 and 45 min of I; membrane PKC activity increased (1.7-fold of baseline, p<0.01, in 60 min of I; 1.8-fold, p<0.01, in 45 min of I; 1.5-fold, p<0.05, in 60 of min I and 120 min of R). From these results, it is concluded that translocation of PKC from the cytosol to myocyte membranes is an important mechanism responsible for PC effect.

Animals↗

PubMed1998

Toward clinical end-user computing: programmable order protocols for efficient human computer interaction.

We have developed and implemented an efficient method of managing routine patient care information as a programmable group order protocol. The purpose of protocol is to minimize a labor-intensive manual computer interaction by grouping clinically related routine orders as a single entity, thus to greatly speed up the time taken for manual entry such as keyboard stroke and/or mouse clicking. User programmability is added to facilitate insertion, deletion and update of order items to be a locally independent operation. A sequence of menu screen is also programmable when a change of standard operation is needed. Department specific order protocols are classified into four categories to improve user convenience. The degree of efficiency is measured by a number of key strokes and entry time. In most cases the time to enter order protocol with correction is found to take less than one minute with less than five key strokes. The method of order protocol entry clearly demonstrates end-user computing capability so that department specific requirements are resolved without resorting to computer department personnel. Flexibility of managing individual physician specific protocols is also beneficial enough to enhance the morale toward a hospital information system currently in use.

Computer Graphics↗

PubMed1998

ABT-594 [(R)-5-(2-azetidinylmethoxy)-2-chloropyridine]: a novel, orally effective antinociceptive agent acting via neuronal nicotinic acetylcholine receptors: II. In vivo characterization.

The antinociceptive effects of ABT-594, a novel nicotinic acetylcholine receptor (nAChR) ligand, were examined in rats in models of acute thermal (hot box) and persistent chemical (formalin test) pain. Also, the effects of ABT-594 treatment on motor function and electroencephalogram (EEG) were determined. In the hot box and formalin test (i.e., phase 1 and 2), acute treatment with ABT-594 (0.03, 0.1 and 0.3 mumol/kg i.p.) produced significant dose-dependent antinociceptive effects. In the hot box, the efficacy of ABT-594 was maintained after a repeated dosing paradigm (5 days b.i.d.i.p.). ABT-594 was fully efficacious in the formalin test when administered before formalin, and also retained significant efficacy (0.3 mumol/kg i.p.) when administered after formalin injection. The antinociceptive effects of ABT-594 in the hot box and formalin tests were attenuated by pretreatment with the nAChR antagonist, mecamylamine, and in animals treated with the nAChR antagonist chlorisondamine, given centrally (10 micrograms/rat i.c.v. 5 days before), but not in animals pretreated with the opioid receptor antagonist, naltrexone. Acute treatment with ABT-594 produced an initial decrease in open-field locomotor activity, which was absent in animals dosed repeatedly (5 days b.i.d.) with ABT-594. Also, acute treatment with ABT-594 decreased body temperature and decreased the amount of time the animals could maintain balance in an edge-balance test. These effects were no longer present in animals dosed repeatedly with ABT-594. At antinociceptive doses, ABT-594 produced activation of free running EEG in contrast to the sedative-like effects of morphine. Full antinociceptive efficacy was maintained in both the hot box and formalin tests after oral administration, whereas the effects on motoric performance were attenuated. In conclusion, these data demonstrate that ABT-594 is a potent antinociceptive agent with full efficacy in models of acute and persistent pain and that these effects are mediated predominately by an action at central neuronal nAChRs. In addition, antinociceptive effects were maintained after repeated dosing, whereas effects of ABT-594 on motor and temperature measures were attenuated in animals treated repeatedly with ABT-594. Thus, compounds acting at nAChRs may represent a novel approach for the treatment of a variety of pain states.

Administration, Oral↗

PubMed1997

Chemoprevention by lycopene of mouse lung neoplasia after combined initiation treatment with DEN, MNU and DMH.

An investigation was conducted to assess the chemopreventive potential of lycopene (LP), a naturally occurring hydrocarbon carotenoid found in tomatoes and their products, administered during the post-initiation stage in a multiorgan carcinogenesis model. One hundred eighteen B6C3F1 mice of both sexes were subjected to combined treatment with diethylnitrosamine (DEN), N-methyl-N-nitrosourea (MNU) and 1,2-dimethylhydrazine (DMH) from day 11 after birth to week 9 (DMD treatment) (groups 1 and 2) or their vehicles (group 3). Then group 1 received LP (25 or 50 ppm in drinking water) for 21 weeks from weeks 11 to 32. Group 2 served as a carcinogen alone control and group 3 was given only LP (25 or 50 ppm). All surviving animals were sacrificed at week 32 and the major organs, including the liver, lung, kidney and colon, were histologically examined. The incidences and multiplicities of lung adenomas plus carcinomas combined in male mice in group 1 receiving 50 ppm LP were significantly decreased as compared to the DMD alone or DMD and 25 ppm LP groups (75.0 versus 18.8%, P < 0.02; 0.94 +/- 0.17 versus 0.25 +/- 0.14, P < 0.001). No such effect was observed for females. Although hepatocellular carcinomas were lacking in the DMD and LP groups while two cases were found in the DMD alone group, this difference was not statistically significant. The values for aberrant crypt foci (ACF) and tumors in the colon and kidney did not show any significant variation among the carcinogen-treated subgroups. The results suggest that LP exerts a chemopreventive effect limited to male lung carcinogenesis when given in the post-initiation stage to B6C3F1 mice.

1,2-Dimethylhydrazine↗

PubMed1997

Characterization of human immunodeficiency virus type 1 integrase mutants expressed in Escherichia coli.

The eight mutant integrase (IN) proteins of human immunodeficiency virus type (HIV-1), which have a single point mutation at a highly conserved central region, were prepared, and characterized in terms of their endonucleolytic activities and disintegration activities in vitro. Mutation of two highly conserved amino acids, Asp116 or Glu152, leads to complete loss of both the activities, suggesting that these two amino acids are directly associated with enzymatic functions. In addition, the mutant of the position Ser147 was found to have highly depressed endonucleolytic activity showing that the reaction was very delayed in comparison with that of the wild type. However, significant disintegration was detected in the mutant Ser147, indicating that the enzymatic mechanisms of the endonucleolytic and disintegration activities are not exactly reverse. The integrase protein with a mutation at the conserved amino acid Asn117 or Gly118 had a slight loss of the endonucleolytic activity, while a mutation at the three positions, Tyr143, Ser153, and Lys159, had no detectable effect on their enzymatic activities. These results indicate that only a few of the conserved amino acids are critical for enzymatic activities.

Amino Acid Sequence↗

PubMed1997

A cDNA encoding a putative SPF1-type DNA-binding protein from cucumber.

A cDNA clone encoding a polypeptide with homology to the novel SPF1 DNA-binding protein of sweet potato has been isolated from a cDNA library from RNA of senescing cucumber (Cucumis sativus, L.) cotyledons. Comparison of the two sequences reveals similar features which may be important in the evolution and function of this protein, including a duplicated region of about 56 amino acids (aa). The first half of the duplicated region is enriched in basic aa and is very highly conserved, both within and between each polypeptide. In contrast, the second half of the duplicated region is poorly conserved within each polypeptide, but highly conserved when cucumber and sweet potato sequences are compared. Southern blot analysis with cucumber DNA shows a simple hybridisation pattern indicating one or very few genes. Northern blot analysis shows that the expression of the cucumber gene increases in cotyledons as they expand and become photosynthetic and remains high in senescence. The possibility that the cucumber SPF1-type protein may be involved in carbohydrate regulation of gene expression is discussed.

Amino Acid Sequence↗

PubMed1997

Potential preventive effects of Chelidonium majis L. (Papaveraceae) herb extract on glandular stomach tumor development in rats treated with N-methyl-N'-nitro-N nitrosoguanidine (MNNG) and hypertonic sodium chloride.

The modifying effects of Chelidonium majis L. (Papaveraceae) herb extract (CH), an analgesic traditionally prescribed for gastric and duodenal ulcer patients, on gastric tumor development were studied in rats given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Sixty-four male 6-week-old Wistar rats were used. Group 1 rats were initially given MNNG (200 mg/kg b.w.) by gavage at days 0 and 14 as well as saturated sodium chloride solution (S-NaCl, 1 ml per rat) every 3 days during weeks 0-3 (six times), and then placed on basal diet containing 0.1 or 0.2% CH for 16 weeks from week 4. Rats of Group 2 and 3 were treated with MNNG together with S-NaCl or saline (0.9% NaCl, 1 ml per rat), respectively, timed as in Group 1 but without further treatment. All surviving animals were killed at week 20 and histopathologically investigated. In the glandular stomach, the number of preneoplastic pepsinogen 1 altered pyloric glands (PAPGs) in the MNNG + S-NaCl-->CH (0.1%) group (Group 1) was significantly smaller than in the MNNG + S-NaCl group (Group 2) (P < 0.02). The incidences of forestomach neoplastic lesions (papillomas and squamous cell carcinomas) also showed a tendency to decrease with the CH treatment. The results thus indicate that CH exerts inhibitory effects on glandular stomach carcinogenesis in the rat, so that it may have potential as a chemopreventive agent for stomach cancer in man.

Animals↗

PubMed1997

Esophageal aspergillosis after bone marrow transplant.

The prolonged immune suppression associated with bone marrow transplants predisposes to fungal infections including Aspergillus. Disseminated aspergillosis occurs in up to 60% of patients with invasive pulmonary aspergillosis; sites of involvement include the brain, gastrointestinal tract, kidney, liver, thyroid, heart, and spleen. There is only one report of isolated esophageal aspergillosis. A recent acute myelogenous leukemia patient had isolated esophageal aspergillosis after bone marrow transplantation which was successfully treated with amphotericin B.

Adult↗

PubMed1997

Pre-emptive ganciclovir treatment can play a role in restoration of hematopoiesis after allogeneic bone marrow transplantation.

We performed pre-emptive ganciclovir therapy on two allogeneic bone marrow transplant (BMT) recipients with myelosuppression associated with cytomegalovirus (CMV) antigenemia after successful engraftment. During the hypoplastic phase, the nucleated cells in the bone marrow and peripheral blood were revealed to be of donor origin by DNA fingerprinting. These two patients had CMV antigen in their peripheral leukocytes. Following the pre-emptive ganciclovir treatment, both of them showed gradual recovery of granulocytes and platelets. They are still alive with stable bone marrow function. From these results, we suppose that infection or reactivation of CMV can suppress bone marrow function after bone marrow transplantation, and the pre-emptive ganciclovir therapy based on the CMV antigenemia may be beneficial if bone marrow function deteriorates after engraftment.

Adolescent↗