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Biomedical subjects

D K Kim

Publications and source records attributed to D K Kim.

At least 145 records · Page 8Linked to original sources
PubMed1999

Moderate hyperhomocyst(e)inemia is associated with the presence of coronary artery disease and the severity of coronary atherosclerosis in Koreans.

To examine whether moderate hyperhomocyst(e)inemia is associated with coronary artery disease and the number of diseased coronary vessels in Koreans, we investigated 201 patients with angiographically documented coronary artery disease and 187 healthy subjects without evidence of stroke and coronary artery disease. The mean plasma total homocysteine in patients was higher than in controls (10.3 micromol/L; 95% confidence interval, 7.0-13.6 vs. 8.9 micromol/L; 6.0-11.8) (p=0.005). The prevalence of moderate hyperhomocyst(e)inemia, defined as the top 90th percentile in controls (13.2 micromol/L), was higher in patients than in controls (23.9% vs. 10.2%, p=0.001). Plasma homocyst(e)ine levels were not correlated to age, body mass index, levels of serum cholesterol, creatinine, and uric acid. Based on multiple logistic regression analyses with adjustment for total cholesterol, hypertension, smoking status, diabetes, age, and body mass index, the adjusted odds ratio of moderate hyperhomocyst(e)inemia for coronary artery disease was 1.53 (95% confidence interval: 1.39-1.65, p=0.0001). Moderate hyperhomocyst(e)inemia, diabetes mellitus, and old age were more prevalent in patients with triple-vessel disease than in single- or double-vessel disease (p=0.02). Multiple logistic regression analysis revealed that moderate hyperhomocyst(e)inemia was a significant predictor of triple-vessel disease with odds ratio of 2.78 (95% confidence interval: 1.08-7.10, p=0.02). We conclude that moderate hyperhomocyst(e)inemia is an independent risk factor for coronary artery disease, and also related significantly to the presence of triple-vessel disease.

Adult↗
PubMed1999

Deficient transcription of mouse mast cell protease 4 gene in mutant mice of mi/mi genotype.

The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF). We reported that expression of the mouse mast cell protease 5 (MMCP-5) and MMCP-6 genes were deficient in cultured mast cells (CMC) derived from mutant mice of mi/mi genotype. Despite the reduced expression of both MMCP-5 and MMCP-6, their regulation mechanisms were different. Because MMCP-5 is a chymase and MMCP-6 a tryptase, there was a possibility that the difference in regulation mechanisms was associated with their different characteristics as proteases. We compared the regulation mechanisms of another chymase, MMCP-4, with those of MMCP-5 and MMCP-6. The expression of the MMCP-4 gene was also deficient in mi/mi CMC. The overexpression of the normal (+) MITF but not of mi-MITF normalized the poor expression of the MMCP-4 gene in mi/mi CMC, indicating the involvement of +-MITF in transactivation of the MMCP-4 gene. Although MMCP-4 is chymase as MMCP-5, the regulation of MMCP-4 expression was more similar to MMCP-6 than to MMCP-5. We also showed the deficient expression of granzyme B and cathepsin G genes in mi/mi CMC. Genes encoding granzyme B, cathepsin G, MMCP-4, and MMCP-5 are located on chromosome 14. Because all these genes showed deficient expression in mi/mi CMC, there is a possibility that MITF might regulate the expression of these genes through a locus control region.

Animals↗
PubMed1999

Biochemical basis for a cholesterol-lowering activity of 2-[2"-(1",3"-dioxolane)]-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6- nitro-2H-1-benzopyran (SKP-450), a novel antihypertensive agent.

Administration (p.o.) of SKP-450, 2-[2"-(1",3"-dioxolane)]-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro-2H- 1-benzopyran, a novel antihypertensive agent, to hypercholesterolemic Syrian hamsters led to a significant reduction in plasma lipids in a dose-dependent manner, i.e., a 10.8% to 29% reduction in low-density lipoprotein cholesterol at doses of 0.3 to 10 mg/kg of SKP-450. SKP-450 was found to specifically inhibit the hepatic microsomal lanosterol 14alpha-methyl demethylase (14alpha-DM) in a competitive manner (Ki:2.65 microM). Furthermore, a dose-dependent decrease in the 14alpha-DM activity by SKP-450 parallelled the cholesterol synthetic rate in vitro in both the rat hepatic S10 fractions (supernatants at 10,000 g; IC50:20 microM) and Chinese hamster ovary cells (IC50:23 microM). However, this phenomenon was not seen in AR45 cells, which are deficient in 14alpha-DM, suggesting that 14alpha-DM is the major target for the inhibitory action of SKP-450 in regard to cholesterol biosynthesis.

Animals↗
PubMed1999

Inhibitory effect of the transcription factor encoded by the mi mutant allele in cultured mast cells of mice.

The mi locus of mice encodes a transcription factor of the basic-helix-loop-helix-leucine zipper protein family (MITF). The MITF encoded by the mutant mi allele (mi-MITF) deletes 1 of 4 consecutive arginines in the basic domain. The mice of mi/mi genotype express mi-MITF, whereas the mice of tg/tg genotype have a transgene at the 5' flanking region of the mi gene and do not express any MITF. To investigate the function of mi-MITF in cultured mast cells (CMCs), we took two approaches. First, mRNA obtained from mi/mi CMCs or tg/tg CMCs was subtracted from complementary (c) DNA library of normal (+/+) CMCs, and the (+/+-mi/mi) and (+/+-tg/tg) subtraction libraries were obtained. When the number of clones that hybridized more efficiently with +/+ CMC cDNA probe than with mi/mi or tg/tg CMC cDNA probe was compared using Southern analysis, the number was larger in the (+/+-mi/mi) library than in the (+/+-tg/tg) library. Second, we compared mRNA expression of six genes between mi/mi and tg/tg CMCs by Northern analysis. The transcription of three genes encoding mouse mast cell proteases was impaired in both mi/mi and tg/tg CMCs. On the other hand, the transcription of three genes encoding c-kit receptor, tryptophan hydroxylase, and granzyme B was markedly reduced in mi/mi CMCs, but the reduction was significantly smaller in tg/tg CMCs. These results indicated the inhibitory effect of mi-MITF on the transactivation of particular genes in CMCs.

Animals↗
PubMed1999

Synthesis and evaluation of 2-amino-9-(1, 3-dihydroxy-2-propoxymethyl)- 6-fluoropurine mono- and diesters as potential prodrugs of ganciclovir.

A series of 2-amino-9-(1,3-dihydroxy-2-propoxymethyl)-6-fluoropurine mono- and diesters, 6a-h, were synthesized as potential prodrugs of ganciclovir and evaluated for their oral ganciclovir bioavailability in rats. Treatment of 2-amino-6-chloro-9-(1, 3-dihydroxy-2-propoxymethyl)purine (4) with Me3N in DMF/THF (1/4) followed by the reaction of the resulting trimethylammonium chloride salt 5 with KF in DMF gave 2-amino-9-(1, 3-dihydroxy-2-propoxymethyl)-6-fluoropurine (2) in 83% yield. Esterification of 2 with an appropriate acid anhydride (Ac2O, (EtCO)2O, (n-PrCO)2O, or (i-PrCO)2O) (6 equiv for 6a-d or 1 equiv for 6e-h) in DMF in the presence of a catalytic amount of DMAP produced the diesters 6a-d in 92-98% yields and the monoesters 6e-h in 37-44% yields. Of the prodrugs tested in rats, the monoisobutyrate 6h achieved the highest ganciclovir bioavailability (45%) that is 15-fold higher than that from ganciclovir (3%), followed in order by the diisobutyrate 6d (42%), the diacetate 6a (41%), the monobutyrate 6g (41%), the monopropionate 6f (39%), the dipropionate 6b (35%), the dibutyrate 6c (35%), and the monoacetate 6e (29%). The prodrugs 6e-h were found to be quite stable at pH 6.0 (t1/2 = >29 days), 7.4 (t1/2 = >7 days), and 8.0 (t1/2 = >2 days) but had relatively short half-lives at pH 1.2 (t1/2 = 60-83 min).

Animals↗
PubMed1999

Role of the inflamed synovial volume of the wrist in defining remission of rheumatoid arthritis with gadolinium-enhanced 3D-SPGR MR imaging.

The purpose of this study was to assess the role of inflamed synovial volume (ISV) in defining a state of remission in rheumatoid arthritis (RA) with contrast-enhanced, fat-suppression, three-dimensional (3D) gradient-recalled acquisition in the steady state with radiofrequency spoiling (SPGR) magnetic resonance (MR) imaging. Sixteen patients with RA (5 remission and 11 non-remission patients) were enrolled in this study. Contrast-enhanced, fat-suppression, 3D-SPGR MR imaging was performed before (n = 12) and after (n = 16) a mean 17 months of disease-modifying antirheumatic drugs (DMARDs). ISV was calculated by using a segmentation method. Statistical analysis of changes in ISVs and residual ISVs between the remission and the non-remission groups was performed. Intra- and inter-observer reproducibility was tested. Residual ISVs and relative changes in ISVs were 3.23 +/- 1.84 cm(3) and 51.4% (range 47.6-55.2%) in the remission group and 6.26 +/- 2. 03 cm(3)and 31.4% (range -73.5-53.5%) in the non-remission group. Both values were significantly different between the two groups (P < 0.05 and 0.05, respectively). Volume measurement showed high reproducibility: Intra- and inter-observer mean percentage errors were 5.04, 7.06, and 5.09%, respectively. Residual ISVs and relative changes in ISVs measured by MR imaging may provide objective and quantitative parameters in defining a state of remission in RA after therapy; however, the clinical utility of these measurements remains to be verified. J. Magn. Reson. Imaging 1999;10:202-208.

Adult↗
PubMed1999

Takayasu arteritis: diagnosis with MR imaging and MR angiography in acute and chronic active stages.

Early diagnosis and treatment of Takayasu arteritis is important in prevention of serious complications. Spin-echo magnetic resonance imaging (MRI) can depict early wall thickening of the aorta and cine MRI can evaluate aortic valve function. Significant enhancement in and around the aorta and carotid arteries is observed on postcontrast MR images in acute phase Takayasu arteritis. In the chronic phase, contrast enhancement in the aortic wall stronger than in the myocardium suggests activity of the disease. Breath-hold contrast-enhanced three-dimensional MR angiography is very effective in noninvasive evaluation of luminal change of aortitis. Contrast-enhanced MRI and MR angiography have an important role in early diagnosis, activity determination, and follow-up of Takayasu arteritis. MRI and MR angiography can be utilized for initial diagnosis of Takayasu arteritis and replace catheterization angiography. J. Magn. Reson. Imaging 1999;10:751-757.

Acute Disease↗
PubMed1999

Comparison of hematopoietic activities of human bone marrow and umbilical cord blood CD34 positive and negative cells.

Although the hematopoietic activities of human CD34+ bone marrow (BM) and cord blood (CB) cells have been well characterized, the phenotype of nonobese-diabetic severe combined immunodeficient (NOD/SCID) mice repopulating cells (SRCs) in CB and BM has not yet been fully examined. To address this issue, various hematopoietic activities were compared in terms of total and CD34+ CB and BM cells. Clonal culture of fluorescence-activated cell sorter (FACS) CD34+ CB and BM cells revealed a higher incidence of colony-forming cells with greater proliferation capacity in CB over BM CD34+ cells. CB CD34+ cells also demonstrated higher secondary plating efficiency over BM cells. In addition, we demonstrated that mice transplanted with CB mononuclear cells (MNCs) showed significantly higher levels of chimerism than those transplanted with BM MNCs. However, recipients of FACS-sorted CD34+ CB cells showed significantly lower levels of chimerism than those that received total CB MNCs, suggesting a role of facilitating cells in the CD34- cell population. To further analyze the role of CD34- cells, the NOD/SCID repopulating ability of FACS-sorted CB CD34-c-kit+Lin- and CD34-c-kit-Lin- cells were examined. However, SRCs were not detected in those cells. Taken together, these data suggest that CB is a better source of hematopoietic stem cells and that there are cells in the CD34- fraction that facilitate repopulation of hematopoiesis in the NOD/SCID environment.

Animals↗
PubMed1999

Inhibitory effect of mast cell-mediated immediate-type allergic reactions by Cichorium intybus.

We investigated the effect of an aqueous extract of Cichorium intybus (CIAE) on mast cell-mediated immediate type allergic reactions. CIAE (0.1-1000 mg kg-1) dose-dependently inhibited systemic anaphylactic reaction induced by compound 48/80 in mice. Especially, CIAE inhibited compound 48/80-induced anaphylactic reaction 100% with the dose of 1000 mg kg-1. CIAE 1000 mg kg-1also significantly inhibited local anaphylactic reaction activated by anti-dinitrophenyl (DNP) IgE. When mice were pretreated with CIAE at a concentration ranging from 0.1 to 1000 mg kg-1, the plasma histamine levels were reduced in a dose-dependent manner. CIAE (1-1000 microg ml-1) dose-dependently inhibited histamine release from the rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cAMP in RPMC, when CIAE (1000 microg ml-1) was added, increased significantly compared with that of control cells. These results indicate that CIAE inhibits mast cell-mediated immediate-type allergic reactions in vivo and in vitro.

Anaphylaxis↗
PubMed1999

Solitary eosinophilic granuloma of the temporal lobe: case report and review of the literature.

A solitary eosinophilic granuloma of the central nervous system is an unusual manifestation of histiocytosis X. A unique case of a solitary eosinophilic granuloma of the right temporal lobe without osseous involvement is described. A 20-year-old man presented with a grand mal seizure. Magnetic resonance imaging demonstrated an intraaxial enhancing mass in the right temporal lobe with marked vasogenic edema. A right temporal craniotomy was performed for resection of the lesion and the diagnosis of an eosinophilic granuloma was confirmed by histopathology. Follow-up MR imaging obtained 5 years following resection demonstrated no recurrence. Solitary eosinophilic granuloma should be considered in the differential diagnosis of enhancing mass lesions affecting the central nervous system. Although the natural history of solitary eosinophilic granulomas remains poorly defined, surgical treatment still remains the mainstay of therapy for these unifocal cerebral lesions.

Adult↗
PubMed1999

Anti-allergic components from the peels of Citrus unshiu.

In a bioassay-guided search for anti-allergic compounds from higher plants of Korea, polymethoxyflavones, 3',4',5,6,7,8-hexamethoxyflavone (1), 5-hydroxy-3',4',6,7,8-pentamethoxyflavone (II) and 3',4',5,7,8,-pentamethoxyflavone (III) have been isolated from the immature peels of Citrus unshiu. Structures of these compounds were elucidated on the basis of spectroscopic techniques. Compounds I and II inhibited dose-dependently histamine release from the rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE.

Animals↗
PubMed1999

A new cytotoxic acyclic diterpene from Carpesium divaricatum.

A new acyclic diterpene (1) and a known acyclic diterpene, 12(S)-hydroxygeranylgeraniol (2) were isolated from the aerial parts of Carpesium divaricatum. The structure of 1 was determined to be (2E,10E)-1,12-dihydroxy-18-acetoxy-3,7,15-trimethylhexadeca- 2,10,14-triene (1) on the basis of spectroscopic studies. Compounds 1 and 2 exhibited cytotoxicity against cultured human tumor cell lines, A549, SK-OV-3, SK-MEL-2, XF498, and HCT15, with ED50 values ranging from 4.3-10.2 micrograms/ml and 4.1-8.3 micrograms/ml, respectively.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Long-term outcome of aqueous shunt surgery in ten patients with iridocorneal endothelial syndrome.

PURPOSE: To report the long-term outcome of ten patients with iridocorneal endothelial (ICE) syndrome who underwent aqueous shunt surgery for uncontrolled glaucoma. DESIGN: Noncomparative, retrospective case series. PARTICIPANTS: The authors reviewed charts of ten patients with ICE syndrome-related glaucoma who underwent aqueous shunt surgery at one institution between 1987 and 1996. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), number of glaucoma medications, and further surgical interventions were measured. RESULTS: With a median follow-up of 55 months, four eyes had adequate IOP control (IOP <21 mm Hg) with one or two medications after the initial aqueous shunt surgery. An additional three eyes achieved adequate IOP control after one or more tube repositionings or revisions of the initial aqueous shunt. In this series, the aqueous shunt surgery most often failed because of blocking of the tube ostium by iris, ICE membrane, or membrane-induced tube migration. CONCLUSION: Aqueous shunt surgery appears to be an effective method for IOP lowering in some eyes with ICE syndrome-related glaucoma when medical treatment or conventional filtration surgeries fail, but additional glaucoma procedures and/or aqueous shunt revisions and tube repositionings are not uncommon.

Adult↗
PubMed1999

Candidate neuroanatomic substrates of psychosis in old-aged depression.

1. The authors investigated the candidate neuroanatomic substrates underlying delusional thought disorder in old-aged depressed patients by using magnetic resonance imaging (MRI), and examined the relationship between volumes for individual brain structures and clinical correlates of particular relevance to depression: executive cognitive impairment and global severity of depression. 2. MR morphometry was performed on nineteen deluded depressed patients and 26 non-deluded depressed patients, all older than 55 years of age. Subjects were administered a neuropsychological test battery and measures of depression. 3. The absolute volume of prefrontal cortex (PFC) was smaller in the deluded depressed group than in non-deluded depressed group (131.79 +/- 37.26 ml vs. 152.65 +/- 26.13 ml, p = 0.03); a difference that was statistically significant even after adjusting for the effect of whole brain volume (p = 0.01). No group differences were observed in the volumes of the basal ganglia, the temporal lobes, the superior temporal gyri, the amygdala-hippocampal complex, the lateral ventricles, or whole brain. The relative volume of PFC correlated inversely and significantly with the index of Wisconsin Card Sorting Test (WCST) performance (r = -0.76, p < 0.01) in depressed patients. 4. PFC may be one of the candidate neuroanatomic substrates underlying delusional thought disorder in old-aged depression.

Aged↗
PubMed1999

Synthesis and evaluation of amino acid esters of 6-deoxypenciclovir as potential prodrugs of penciclovir.

The amino acid ester derivatives of 6-deoxypenciclovir, 11-20, were synthesized as potential prodrugs of penciclovir, and were evaluated for their oral penciclovir bioavailability in mice and rats. Esterification of 6-deoxypenciclovir with N-carbobenzyl-oxyglycine, -L-alanine, -L-valine, -L-leucine, or -L-isoleucine (3.75equiv.) using conventional coupling method (DCC/DMAP) afforded the mono-O-ester derivatives 1-5 in 47-55% yields as a mixture of two diastereomers along with the di-O-ester derivatives 6-10 in 20-29% yields. Reductive cleavage of carbobenzyloxy (Cbz) group (10% Pd/C, 1 atmosphere of H2, room temperature in methanol) followed by subsequent treatment of the resulting free amine with methanolic HCI solution provided the mono-O-ester derivatives 11-15 as di-HCl salt in 51-98% yields and the di-O-ester derivatives 16-20 as tri-HCl salt in 65 98% yields. Of the prodrugs tested in mice and rats, 6-deoxypenciclovir O-L-valinate (13), O-L-isoleucinate (15), and O,O-di-glycinate (16) showed significantly higher urinary recovery of penciclovir compared with that of penciclovir, but those are somewhat lower than that of famciclovir.

Acyclovir↗
PubMed1999

Synthesis and evaluation of 2-amino-6-fluoro-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine mono- and diesters as potential prodrugs of penciclovir.

2-Amino-6-fluoro-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine (7), and its mono- and diesters 8-15 were prepared and evaluated for their potential as prodrugs of penciclovir. Treatment of 2-amino-6-chloro-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine (5) with trimethylamine in THF followed by a reaction of the resulting trimethylammonium chloride salt 6 with KF in DMF afforded 2-amino-6-fluoro-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine (7) in 80% yield. Esterification of 7 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 produced the mono-esters 8-11 in 42-45% yields and diesters 12-15 in 87-99% yields. Of the prodrugs tested in rats, the monoisobutyrate 11 was the most efficiently absorbed and metabolized to 7, showing the mean maximum total concentration of penciclovir (5.5 microg/mL) and 7 (10.8 microg/mL) in the blood was much higher than the mean maximum concentration of penciclovir (11.5 microg/mL) from famciclovir. However, the mean concentrations of penciclovir from 11 were lower than those from famciclovir because of the limited conversion of a major metabolite 7 to penciclovir by adenosine deaminase.

Acyclovir↗
PubMed1999

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

A series of 2-amino-9-(3-acyloxymethyl-4-alkoxycarbonyloxybut-1-yl)purin es (1-8) and 2-amino-9-(3-alkoxycarbonyl-oxymethyl-4-alkoxycarbonyloxybut -1-yl)purines (9-12) were synthesized as potential prodrugs of penciclovir. Treatment of 6-deoxypenciclovir with trimethyl orthoacetate or triethyl orthopropionate (1.2 equiv) in DMF in the presence of p-TsOH.H2O (0.1 equiv) followed by quenching with excess H2O gave the corresponding mono-O-acetyl or mono-O-propionyl compound, 17 or 18, in excellent yields of 95 and 92%, respectively. Reactions of 17 or 18 with an appropriate alkyl (Me, Et, n-Pr, and i-Pr) 4-nitrophenyl carbonate (1.2 equiv) in pyridine in the presence of a catalytic amount of DMAP (0.1 equiv) at 80 degrees C afforded the monoacyl, monocarbonate derivatives of 6-deoxypenciclovir, 1-8, in 86 94% yields. Similar reactions of 6-deoxypenciclovir with 2.1 equiv of alkyl 4-nitrophenyl carbonate produced the dicarbonate derivatives 9 12 in 81-83% yields. Of the prodrugs tested in rats, 2-amino-9-(3-acetoxymethyl-4-isopropoxycarbonyloxybut-1-yl)purine (4) achieved the highest mean urinary recovery of penciclovir (36%), followed in order by compounds 2 (35%), 6 (35%), 7 (34%), 10 (34%), 8 (32%), 3 (32%), and famciclovir (31%). The mean urinary recovery of penciclovir and concentrations of penciclovir in the blood from 4 in mice were also slightly higher than those from famciclovir. The in vivo antiviral efficacy of 4 in HSV-1-infected normal BALB/c mice was higher than those of famciclovir and valaciclovir in terms of mortality (100, 80, and 40%) and mean survival time ( > 21, 13+/-5.0 (SEM), and 13+/-1.6 days). Compound 4 demonstrated an effective anti-hepadnaviral response with intrahepatic viral load being reduced by 90%, the viral supercoiled DNA levels reduced by 70% and Pre-S expression inhibited by 30% against duck hepatitis B virus (DHBV) in vivo, and did not cause any significant hepatotoxicity after 4 weeks of treatment.

Acyclovir↗