Biomedical subjects

D K Kim

Publications and source records attributed to D K Kim.

At least 181 records · Page 10Linked to original sources

PubMed1998

Synthesis and evaluation of 2-amino-9-(3-hydroxymethyl-4-alkoxycarbonyloxybut-1-yl)purines as potential prodrugs of penciclovir.

A series of 2-amino-9-(3-hydroxymethyl-4-alkoxycarbonyloxybut-1-yl)purines (4-10) and 2-amino-9-(2-(2-oxo-1,3-dioxan-5-yl)ethyl)purine (1) were synthesized as potential prodrugs of penciclovir and evaluated for their oral penciclovir bioavailability in mice and rats. Treatment of 2-(2-benzyloxyethyl)propane-1,3-diol (11) with 1,1'-carbonyldiimidazole in THF followed by hydrogenolytic removal of the benzyl group of the resulting cyclic carbonate 12 gave 5-(2-hydroxyethyl)-1,3-dioxan-2-one (13). Mesylation of the alcohol 13 and then a coupling reaction of the resulting mesylate 14 with 2-amino-6-chloropurine using anhydrous Cs2CO3 in DMF afforded 2-amino-6-chloro-9-(2-(2-oxo-1,3-dioxan-5-yl)ethyl)purine (16) after purification by flash column chromatography on silica gel using EtOAc/MeCN/Et3N as eluent. Hydrogenation of the 6-chloro cyclic carbonate 16 followed by a ring-opening reaction of the 6-deoxy cyclic carbonate 1 in a mixture of an appropriate alcohol and CHCl3 using activated SiO2 as a Lewis acid afforded the corresponding alkyl monocarbonate derivatives 3-10 in fair to good yields. Of the prodrugs tested in mice, the isopropyl monocarbonate 6 achieved the highest mean urinary recovery of penciclovir (53%), followed in order by the propyl monocarbonate 5 (51%), the isopentyl monocarbonate 10 (51%), the ethyl monocarbonate 4 (50%), and famciclovir (48%). In rats, the methyl monocarbonate 3, 4, 6, the n-butyl monocarbonate 7, and 10 (39-41%) showed levels of mean urinary recovery of penciclovir similar to that from famciclovir (40%). The alkyl monocarbonates 4-10 were found to be quite stable in the aqueous buffer solutions, and among them, 6 was the most stable with the half-lives (t1/2) of 88, >200, 61, and 26 days at pH 1.2, 6.0, 7.4, and 8.0, respectively. In addition, 6 was highly soluble in H2O (138.8 mg/mL, 20 degrees C).

Acyclovir↗

PubMed1998

Systematic method to obtain novel genes that are regulated by mi transcription factor: impaired expression of granzyme B and tryptophan hydroxylase in mi/mi cultured mast cells.

The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors (hereafter called MITF). We have reported that the expression of several genes was impaired in cultured mast cells (CMCs) of mi/mi genotype, and demonstrated the involvement of MITF in the transcription of these genes. To obtain new genes whose transcription may be regulated by MITF, we prepared a subtracted cDNA library using +/+ and mi/mi CMCs. We found two clones carrying the granzyme (Gr) B and tryptophan hydroxylase (TPH) cDNAs in the subtracted library. The expression of the Gr B and TPH genes decreased in mi/mi CMCs, and recovered to nearly normal level by the overexpression of normal (+) MITF but not of mutant (mi) MITF. The +-MITF bound three and one CANNTG motifs in the Gr B and TPH promoters, respectively, and transactivated these two genes, indicating the involvement of +-MITF in their expression. Because TPH is the rate-limiting enzyme for serotonin synthesis, we examined the serotonin content of +/+ and mi/mi CMCs. The serotonin content was significantly smaller in mi/mi CMCs than in +/+ CMCs. The introduction of +-MITF but not of mi-MITF normalized the serotonin content in mi/mi CMCs.

Animals↗

PubMed1998

Suppression of inflammatory responses by surfactin, a selective inhibitor of platelet cytosolic phospholipase A2.

Surfactin inhibits platelet and spleen cytosolic 100 kDa phospholipase A2 (PLA2). In contrast, this same compound enhances rat platelet group II PLA2 activity by approximately 2-fold and slightly increases group I PLA2 activity from porcine pancreas and Naja naja venom in vitro. Surfactin does not affect a Ca2+ -independent PLA2 partially purified from bovine brain. Thus, this compound inhibits selectively the cytosolic form of PLA2. Based on in vitro studies utilizing preincubation of surfactin with the enzyme, dialysis, and increased concentrations of substrates, the inhibitory effect of surfactin appears to be due to a direct interaction with the enzyme. Linear regression analysis of the linear portion of a concentration-response curve reveals an IC50 of 8.5 microM. To further determine the inhibitory pattern, a Dixon plot was constructed to show that the inhibition by surfactin is competitive, but not uncompetitive, with an inhibition constant of Ki = 4.7 microM in 50 mM Tris-HCl buffer, pH 8.0, at 37 degrees. Surfactin blocked non-stimulated and calcium ionophore A23187-stimulated release of arachidonic acid from monkey kidney CV-1 cells, which contain a cytosolic 100 kDa PLA2 as the major activity, as shown in an anionic exchange DEAE-5PW high performance liquid chromatography profile and western blotting analysis. Surfactin ameliorated inflammation induced by several chemicals. That is, it exhibited in vivo anti-inflammatory activity in several tested inflammatory reactions including 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema, carrageenan-induced rat paw edema, and acetic acid-induced mouse writhing. These results demonstrate that surfactin is a selective inhibitor for cytosolic PLA2 and a putative anti-inflammatory agent through the inhibitory effect produced by direct interaction with cytosolic PLA2, and that inhibition of cytosolic PLA2 activity may suppress inflammatory responses.

Acetic Acid↗

PubMed1998

Nonclassic measles infections in an immune population exposed to measles during a college bus trip.

This study investigated the frequency of mild or asymptomatic measles infections among 44 persons exposed to a student with measles during a 3-day bus trip using two buses. Questionnaires and serum samples were obtained 26-37 days after the trip. All participants had detectable measles-neutralizing antibodies, and none developed classic measles symptoms. Ten persons (23%) were IgM positive for measles, indicating recent infection. Among previously vaccinated IgM-negative persons, those who rode on bus A with the index case-patient had significantly higher microneutralization titers than those on bus B (P= .001), suggesting that some persons on bus A were infected but were IgM negative at the time of the study. Mild or asymptomatic measles infections are probably very common among measles-immune persons exposed to measles cases and may be the most common manifestation of measles during outbreaks in highly immune populations.

Adolescent↗

PubMed1998

A new epoxynaphthoquinol from Rumex japonicus.

A new epoxynaphthoquinol derivative, 3-acetyl-2-methyl-1, 5-dihydroxy-2,3-epoxynaphthoquinol (I), was isolated from the root of Rumex japonicus. The structure was elucidated by high field 1D and 2D NMR techniques.

Magnetic Resonance Spectroscopy↗

PubMed1998

Isolation of a multidrug resistance inhibitor from Aconitum pseudo-laeve var. erectum.

To overcome multidrug resistance (MDR) in cancer chemotherapy, we prepared various plant extracts and searched for a component which is effective for inhibition of MDR. MDR inhibition activity was determined by measuring cytotoxicity to MDR cells using multidrug resistant human fibrocarcinoma KB V20C, which is resistant to 20 nM vincristine and expresses high level of mdr1 gene. Of various plant extracts, the MeOH extract of the root of Aconitum pseudo-laeve var. erectum was found to have potent inhibitory activity on MDR. The bioassay-guided fractionation of the MeOH extract of the plant led to the isolation of an alkaloid, lycaconitine, as an active principle. And the IC50 of lycaconitine for KB V20C cells was 74 micrograms/ml.

Alkaloids↗

PubMed1998

Thymol derivatives from Carpesium divaricatum.

Four thymol derivatives, 2,5-dimethoxythymol (1), 2-methoxythymol isobutyrate (2), 10-isobutyloxy-8,9-epoxythymolisobutyrate (3) and 10-(2-methylbutyloxy)-8,9-epoxythymolisobutyrate (4) were isolated from the aerial parts of Carpesium divaricatum. The structures were elucidated by high field 1D and 2D NMR techniques.

Asteraceae↗

PubMed1998

A furan derivative from Cornus officinalis.

Dimethyltetrahydrofuran cis-2,5-dicarboxylate a furan derivative has been isolated from the fruits of Cornus officinalis, and it was isolated for the first time in the nature. The structure was elucidated by NMR spectroscopic techniques.

Dicarboxylic Acids↗

PubMed1998

Influence of exposure and infusion times on the cytotoxicity and pharmacokinetics of cis-malonato[(4R, 5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II) .

The effect of exposure time on the in vitro cytotoxicity of a new platinum complex, cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolan e]platinum(II) (SKI 2053R) and cisplatin (CDDP) toward two human lung-adenocarcinoma cell lines (PC-9, PC-14) and two human stomach-adenocarcinoma cell lines (KATO III, MKN-45) was investigated by variation of the exposure time (1, 4, 12, and 24 h) and drug concentration to yield a constant product of drug concentration times exposure time (C x T). Exposure of cancer cells to low concentrations of SKI 2053R for 12 or 24 h resulted in a greater killing effect than did 1- or 4-h exposure to 24- or 6-fold higher concentrations; the inhibitory effects of SKI 2053R on the colony formation of all tumor cell lines except for KATO III were significantly increased with increasing exposure time (P < 0.05). However, the inhibitory effects of CDDP against all tumor cell lines tested except for PC-14 were inversely correlated with increasing exposure time (P < 0.05). The intracellular accumulation of SKI 2053R and CDDP was measured under the same conditions used in the cell-survival assay using MKN-45 cells. The amount of platinum accumulated from SKI 2053R into MKN-45 cells was greater for the treatment involving low concentrations and long-term exposures (12 and 24 h) than for that using high concentrations and short-term exposures (1 and 4 h) at the constant C x T values; however, the increased accumulation of CDDP was more prominent as the concentration was increased, even if the exposure time became shorter. The pharmacokinetics studies of SKI 2053R following 1-, 4-, 12-, and 24-h infusions were performed in beagle dogs. A single dose of SKI 2053R (5.0 mg/kg) was successively given over various infusion periods to three beagle dogs at 3-week intervals. The peak levels of ultrafiltrable platinum observed for SKI 2053R at the 1-, 4-, 12-, and 24-h infusions were 3.10+/-0.49 (mean +/- SD), 1.24+/-0.06, 0.43+/-0.07, and 0.25+/-0.04 microg/ml, respectively. The mean binding ratios of platinum from SKI 2053R to plasma protein at the end of 1-, 4-, 12-, and 24-h infusions were approximately 91%, 73%, 53%, and 51%, respectively. The steady-state level of free platinum was maintained during long-term infusions (12 and 24 h) after short periods (1-3 h) from the start of the infusion. This study strongly suggests that the therapeutic efficacy of SKI 2053R given by continuous long-term infusion should be investigated in future clinical studies.

Adenocarcinoma↗

PubMed1998

Alteration of protease expression phenotype of mouse peritoneal mast cells by changing the microenvironment as demonstrated by in situ hybridization histochemistry.

Mouse mast cell protease (MMCP) mRNA expression was examined by in situ hybridization histochemistry. Peritoneal mast cells (PMCs) of WBB6F1-(+/+) mice expressed MMCP-2, MMCP-4, MMCP-5, and MMCP-6 mRNAs, but did not express MMCP-1 mRNA. When proliferation of PMCs was induced by culturing them in methylcellulose with T cell-derived cytokines, cells in mast cell colonies expressed MMCP-1 mRNA. These mast cells were transferred to a suspension culture to induce further proliferation. The phenotype of the resulting PMC-derived cultured mast cells was similar to that of bone marrow-derived cultured mast cells. When 10(5) PMC-derived cultured mast cells or 10(5) bone marrow-derived cultured mast cells were injected into the stomach wall of mast cell-deficient WBB6F1-W/Wv mice, mast cells that appeared in the mucosa and muscularis propria were similar to mast cells in the stomach of intact WBB6F1-(+/+) mice, indicating the injected cells adapted to a new tissue environment. In contrast, when 10(5) PMCs were injected into the stomach wall of WBB6F1-W/Wv mice, the injected PMCs did not adapt to the mucosa. When 20 PMCs were injected, they proliferated and adapted to the mucosal environment. The present results suggest that PMCs adapt to new environments when proliferation occurs before redifferentiation.

Animals↗

PubMed1998

Traumatic leptomeningeal cyst in an adult: a case report and review of the literature.

BACKGROUND: Traumatic leptomeningeal cyst as a complication of skull fractures was initially thought to occur primarily in the pediatric population. The occurrence of a traumatic leptomeningeal cyst in the adult population is rare. CASE DESCRIPTION: A lump in the right parietal region of this 53-year-old man prompted a computed tomography (CT) scan. The patient denied any symptoms and was in good health. Examination confirmed a firm, nontender, nonpulsatile mass in the right parietal region of the skull. The CT scan demonstrated a 4 x 3 cm area of irregular bone destruction involving both the inner and outer table of the skull. At operation a distinctly raised paper-thin outer table was noted, and underneath was a soft, tan-colored mass, which measured approximately 2 x 2 cm and was connected to the underlying brain through a 1 cm dural defect. The extradural portion of the mass was amputated, the dura repaired with a pericranium patch, the skull defect was repaired with a split thickness bone graft, and the final pathology was congruent with gliotic brain. CONCLUSION: Although rare, this case demonstrates a traumatic leptomeningeal cyst in an adult.

Adult↗

PubMed1998

Synthesis and evaluation of 2-amino-6-fluoro-9-(2-hydroxyethoxymethyl)purine esters as potential prodrugs of acyclovir.

2-Amino-6-fluoro-9-(2-hydroxyethoxymethyl)purine (2) and its ester derivatives 4a-d were synthesized as potential prodrugs of acyclovir, and were evaluated for their oral acyclovir bioavailability in rats and in vivo antiviral efficacy in HSV-1-infected mice. Treatment of 2-amino-6-chloro-9-(2-hydroxyethoxymethyl)purine (3) with trimethylamine in THF/DMF (4:1) followed by a reaction of the resulting trimethylammonium chloride salt 5 with KF in DMF gave 2 in 78% yield. Esterification of 2 with an appropriate acid anhydride (Ac2O, (EtCO)2O, (n-PrCO)2O, or (i-PrCO)2O) in DMF in the presence of a catalytic amount of DMAP at room temperature produced the esters 4a-d in 90-98% yields. Of the prodrugs tested in rats, the isobutyrate 4d achieved the highest mean urinary recovery of acyclovir (51%) that is 5.7-fold higher than that of acyclovir (9%) and comparable to that of valacyclovir (50%). The prodrug 4d protected dose-dependently the mortality of HSV-1-infected mice, and the group treated with 4d at a dose of 400 mg/kg showed the longest mean survival day (14.6+/-3.1 days) (mean+/-S.D.).

Acyclovir↗

PubMed1998

A viral gastroenteritis outbreak associated with person-to-person spread among hospital staff.

OBJECTIVE: To identify the etiologic agent and risk factors associated with a hospital ward outbreak of gastroenteritis. SETTING: A regional referral hospital in upstate South Carolina. METHODS: We reviewed patient charts, surveyed staff, and tested stool from acutely ill persons. A case was defined as diarrhea and vomiting in a staff member or patient from January 5 to 13, 1996. RESULTS: The initial case occurred on January 5 in a staff nurse who subsequently was hospitalized on the ward and visited by many staff colleagues. The staff were at a significantly greater risk for gastroenteritis than were patients (28/89 [31%] vs 10/91 [11%]; relative risk [RR], 2.9; 95% confidence interval [CI95], 1.5-5.5). All 10 case-patients had been exposed to case-nurses (assigned nurses who were primary caretakers), and eight had documented exposure to case-nurses 1 to 2 days before their illness. Patients exposed to case-nurses had a significantly increased risk of illness (8/57 [14%] vs 0/32; RR, >4.5; CI95, undefined). Neither staff nor patients had significantly increased risk from food, water, ice, or exposure to case-patients. Electron microscopy identified small round-structured viruses (SRSVs) in nine of nine stool samples. CONCLUSION: This nosocomial outbreak of gastroenteritis was likely caused by SRSVs introduced by a staff member and spread via person-to-person transmission from and among staff. The potential for spread of SRSV-associated gastroenteritis from and among staff should be considered in developing strategies to prevent similar outbreaks in hospital settings.

Adult↗

PubMed1998

Engraftment of human myelodysplastic syndrome derived cell line in transgenic severe combined immunodeficient (TG-SCID) mice expressing human GM-CSF and IL-3.

A transgenic SCID (TG-SCID) mouse expressing the human cytokines interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) has been generated with the aim of making a model system allowing the in vivo proliferation of human hematopoietic cells. Using TG-SCID mice expressing high levels (30-35 ng/ml in the serum) of human GM-CSF and IL-3, we attempted to engraft a human myeloid leukemia cell line, F-36P, derived from a myelodysplastic syndrome (MDS) patient. When F-36P cells were transferred intravenously into sublethally irradiated TG-SCID mice, extensive proliferation of F-36P cells was found 4-6 wk later. Successful engraftment, however, required the preadministration of a monoclonal antibody to mouse interleukin-2 receptor (IL-2R) beta chain, neutralizing NK activity. Surprisingly, all the transplanted TG-SCID mice engrafted with F-36P cells developed hind leg paralysis approximately 6 wk after transfer. Histological analysis demonstrated extensive invasion and formation of osteolytic lesions by the F-36P cells in the vertebrae. These data indicate that transgenic SCID mice expressing human IL-3 and GM-CSF provide a useful system for the study of human leukemia. In addition, NK cells appear to play an important role in rejection of human cells.

Animals↗

PubMed1998

An Asian multicenter clinical trial to assess the efficacy and tolerability of acarbose compared with placebo in type 2 diabetic patients previously treated with diet. Asian Acarbose Study Group.

OBJECTIVE: To assess the efficacy, safety, and tolerability of acarbose versus placebo during a 24-week treatment period in Asian type 2 diabetic patients with dietary failure. RESEARCH DESIGN AND METHODS: After a 6-week screening period, 126 multiethnic Asian type 2 diabetic patients (64 men, 62 women; mean age +/- SD, 53.4 +/- 10 years) were randomized to receive acarbose (n = 63) or placebo (n = 63). The dosage was increased from 50 mg t.i.d. at week 0 to 100 mg t.i.d. at week 4. Patients were then followed up at weeks 10, 16, and 24. At each visit, body weight, blood pressure, and metabolic indexes were measured. At weeks 0 and 24, fasting plasma glucose and insulin were measured before and 1 h after the administration of an individually tailored breakfast. RESULTS: Using the intention-to-treat analysis, there were greater reductions in (mean [95% CI]) HbA1c (-0.70 [-1.00 to -0.39] vs. -0.27% [-0.54 to 0]; P = 0.04), fasting plasma glucose (-0.37 [-0.75 to 0.02] vs. 0.41 mmol/l [-0.08 to 0.90]; P = 0.017) and 1-h plasma glucose (-0.77 [-1.44 to -0.10] vs. 0.65 mmol/l [-0.07 to 1.36]; P = 0.05) in the acarbose group compared with the placebo group. With acarbose treatment, 78% of patients achieved an HbAlc < 8% compared with 56% in the placebo group (P = 0.003). There was a greater reduction in body weight (-1.31 [-2.46 to -0.15] vs. 0.16 kg [-3.36 to 0.10]; P = 0.02) and higher incidence of flatulence (56 vs. 37%; P = 0.032) in the acarbose than in the placebo group. Using baseline HbA1c and race as covariates, there were no significant interethnic differences in treatment responses (P = 0.232 for treatment-race interaction; P < 0.001 for treatment effect). The dropout rates were similar between the two groups (acarbose, 11 of 63; placebo, 6 of 63). There were no significant laboratory adverse events in either group. CONCLUSIONS: In this multicenter study involving six ethnic groups, acarbose 100 mg t.i.d. was an effective, safe, and generally well-tolerated therapy in Asian type 2 diabetic patients with dietary failure. In some patients with troublesome gastrointestinal symptoms, a lower dosage may be necessary.

Acarbose↗

PubMed1998

Effectiveness of prenatal ultrasonography in detecting fetal anomalies and perinatal outcome of anomalous fetuses.

A retrospective study was performed over a 5-year period (1990-94) to evaluate the effectiveness of prenatal ultrasonography in terms of sensitivity, specificity, and predictive values in detecting fetal anomalies by comparing prenatal ultrasonic results with anomalies found in neonates and the perinatal outcome of anomalous fetuses. Minor congenital anomalies as listed and defined in the Eurocat Register were excluded. From a total of 5544 singletons, 4819 had at least one ultrasound scan (87%), of which 3004 at low risk and 1815 (38%) at high risk for anomalies had routine screening (RS) and indicated scanning (IS), respectively. A total of 136 fetuses were structurally abnormal (2.82%, RS and IS: 0.77% and 6.23%) and 200 major anomalies (RS and IS: 37 and 163) were recorded. The overall sensitivity of the ultrasound test was 78.7% (RS and IS: 34.8% and 87.6%, P < 0.01) for abnormal fetuses and 58.0% (RS and IS: 29.7% and 64.4%, P < 0.01) for anomalies. The overall specificity was 99.9% and the positive and negative predictive values were 97.3% and 99.4%, respectively; these values did not differ significantly between the two groups. The sensitivity of ultrasound for the detection of abnormal fetuses before 24 weeks was 22.8% (RS and IS: 13.0% and 24.8%) which was associated with a 61% (25/41) termination rate (RS and IS: 25% and 75.9%, P < 0.01) and a 24.4% (10/41) postnatal survival rate (RS and IS: 41.7% and 17.2%). The overall survival rate following pre- and postnatal correction of anomalies was 44.9% (RS and IS: 60.9% and 41.6%). For the detection of fetal anomalies anatomic ultrasound scanning is necessary during pregnancy, irrespective of pregnancy condition. Early detection of fetal anomalies could offer the option of pregnancy termination.

Abortion, Induced↗

PubMed1998

Pheochromocytoma complicated with cardiomyopathy after delivery--a case report and literature review.

Pheochromocytoma in pregnancy is very rare but it is associated with very high maternal and fetal mortality. Therefore, it is important to include pheochromocytoma in the differential diagnosis of hypertension associated with pregnancy. It is difficult to make a diagnosis of pheochromocytoma in pregnancy before delivery. The characteristic symptoms of pheochromocytoma could be initiated during delivery because the process of delivery, general anesthesia, fetal movement, induce acute surge of catecholamine release, which could also induce cardiomyopathy. Early diagnosis and intensive care can affect the prognosis of cardiomyopathy induced by pheochromocytoma. Proper management with alpha-blockade, beta-blockade and angiotension converting enzyme inhibitor could acutely reverse the course of cardiomyopathy.

Adrenal Gland Neoplasms↗

PubMed1998

The CVC removal distress syndrome: an unappreciated complication of central venous catheter removal.

The removal of a central venous catheter (CVC) can be complicated by rare but potentially life-threatening neurocardiopulmonary distress. The clinical courses of eight patients who had CVC removal complications are reviewed. Seven patients had catheter removal from the right internal jugular vein, and one from the right subclavian vein. The complications occurred after complete removal of the catheter (four patients), after guidewire replacement for catheter change (three patients), and after detachment of the hemostasis side port of the Swan introducer during sheath removal (one patient). Each of them had more than one complication. The major complications were: neurologic paresis or coma (four patients), respiratory failure (four patients), and shock (two patients). One patient died of pulmonary sepsis. The overall mortality rate was 12.5 per cent. Guidelines for safe removal of central venous catheters are proposed. Possible mechanisms of the complications are discussed. We refer to the observed complications as the CVC removal distress syndrome.

Adult↗