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Biomedical subjects

Y Kim

Publications and source records attributed to Y Kim.

At least 415 records · Page 23Linked to original sources
PubMed1998

Inclusion complexation of ziprasidone mesylate with beta-cyclodextrin sulfobutyl ether.

Ziprasidone is an antipsychotic agent indicated primarily for the treatment of schizophrenia. An intramuscular dosage form of ziprasidone was developed using beta-cyclodextrin sulfobutyl ether (SBECD) to solubilize the drug by complexation. Inclusion complexation of ziprasidone mesylate (ZM) with SBECD was studied by circular dichroism (CD) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy, Monte Carlo simulations, phase-solubility studies, and counterion titration. The results of the studies indicate that ZM, of which the counterion is not fully dissociated from the drug, forms a 1:1 inclusion complex with SBECD with the benzisothiazole group positioned in the cavity. A mathematical model was developed to calculate stability constants of inclusion complexes for the ion pair (Z+M-:SBECD) and the dissociated ionic form (Z+:SBECD) of ZM; the values were 7892 and 957 M(-1), respectively. The model also allowed the dissociation constants of noncomplexed and complexed ZM to be calculated; the value of the former is 8-fold greater than the value of the latter. These results indicate that the inclusion complex formation of the ion pair is favored over that of the dissociated ionic form of ZM, and that the dissociation of ZM is suppressed by inclusion complexation with SBECD.

Antipsychotic Agents↗
PubMed1998

Acute lymphoblastic leukemia with maturation--a new entity with clinical significance.

The diagnosis of 'ALL with maturation' (ALLm) is proposed. One hundred and one patients with untreated ALL were entered into this study. The diagnosis of ALLm was made when more than 20% of all nucleated elements in the bone marrow showed maturation beyond prolymphocytes by light microscopic examination. The mature-appearing leukemic cells showed the same immunophenotype to remaining lymphoblasts. The number of ALLm cases was 19 (18.8%). The mean age at presentation of ALLm was 29 +/- 18, older than that of 18 +/- 16 of the remaining typical ALL (ALLt) (P = 0.015). Remission was induced with daunorubicin, vincristine, prednisone and L-asparaginase. Only two of 19 ALLm patients achieved CR after 4 weeks induction chemotherapy. In contrast, 57 of 82 (69.5%) ALLt patients achieved CR after the same induction chemotherapy. There was no significant difference in immunophenotype of ALLm compared with ALLt. Labeling index of DNA topoisomerase IIalpha (TopoLI) was studied by immunohistochemistry. Initial TopoLI of ALLm (221 +/- 147) was much lower than that of ALLt (609 +/- 262, P = 0.005). Furthermore, the remaining leukemic cells after chemotherapy were not labeled with anti-DNA topoisomerase IIalpha. The P53 protein was expressed in nine of 18 ALLm cases (50.0%) and P-glycoprotein was not expressed in ALLm cases. Twelve of 19 ALLm cases were studied for carrying bcr/abl fusion by karyotyping and/or fluorescent in situ hybridization. Only two cases revealed bcr/abl fusion. In conclusion, ALLm is a separate entity of ALL which has a very poor clinical course and is independent of other prognostic factors. The morphologically mature leukemic cells are in resting GO phase.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

A model of autosomal recessive Alport syndrome in English cocker spaniel dogs.

BACKGROUND: Dogs with naturally occurring genetic disorders of basement membrane (type IV) collagen may serve as animal models of Alport syndrome. METHODS: An autosomal recessive form of progressive hereditary nephritis (HN) was studied in 10 affected, 3 obligate carrier, and 4 unaffected English cocker spaniel (ECS) dogs. Clinical, pathological, and ultrastructural features of the disease were characterized. Expression of basement membrane (BM) proteins was examined with an immunohistochemical technique using monospecific antibodies. RESULTS: Affected dogs had proteinuria and juvenile-onset chronic renal failure. Glomerular basement membrane (GBM) thickening and multilamellation typical of HN were observed in all renal specimens obtained from proteinuric dogs, and severity of GBM ultrastructural abnormalities varied with the clinical stage of disease. Expression of alpha3(IV) and alpha4(IV) chains was totally absent in the kidney of affected dogs. Expression of alpha5(IV) and a6(IV) chains was normal in Bowman's capsule, collecting tubular BM and epidermal BM of affected dogs. The alpha5(IV) chain was not expressed in distal tubular BM of affected dogs. Expression of alpha5(IV) chains was markedly reduced but not absent, and expression of alpha6(IV) chains was present in GBM of affected dogs. Expression of alpha1-alpha2(IV) chains in GBM of affected dogs was increased. Features of obligate carriers were similar to those of unaffected dogs. CONCLUSIONS: We conclude that HN in ECS dogs is a naturally occurring animal model of autosomal recessive Alport syndrome. However, it differs from human disease in the persistence of alpha5(IV) chains in GBM and in the appearance of a6(IV) chains in GBM.

Animals↗
PubMed1998

Redox regulation of renal DNA synthesis, transforming growth factor-beta1 and collagen gene expression.

Growth and injury represent recurrent and related themes in the study of progressive renal disease. We have previously demonstrated that a prooxidant diet, one deficient in antioxidants, selenium and vitamin E, induces renal enlargement, proteinuria, mild tubulointerstitial disease and diminished glomerular filtration rate (GFR). Our present study represents continued examination of these processes. We demonstrate that these diets increase thymidine incorporation into DNA and net DNA content in renal tissue, and induce expression of the mRNA for the proto-oncogene, c-myc, and the histone, H2b. We localize increased DNA synthesis as occurring mainly in the distal renal tubular epithelium. These deficient kidneys also exhibit interstitial expansion that parallels the pattern of DNA synthesis in that both processes are more prominent in the medulla than in the cortex. mRNAs for collagens I, III and IV in conjunction with transforming growth factor-beta1 (TGF-beta1) are up-regulated in the kidney in rats maintained on the deficient diet. In complementary in vitro studies, the exposure of rat kidney fibroblasts, NRK 49F cells, to noncytolytic doses of hydrogen peroxide, induces collagen III, collagen IV and TGF-beta1 mRNA. Induction of these genes is also observed in mesangial cells so exposed to noncytolytic doses of hydrogen peroxide. A final aspect of our study was the examination of renal generation of hydrogen peroxide and the profile of the hydrogen peroxide-degrading enzymes. Deficient kidneys exhibit increased mitochondrial generation of hydrogen peroxide independent of oxygen consumption but in conjunction with suppression of glutathione peroxidase mRNA and activity. Lipid peroxidation was increased twofold in the cortex and medulla of the deficient kidneys. Surprisingly, catalase activity, measured in the cortex and medulla, and whole kidney catalase mRNA were also reduced in rats maintained on the antioxidant deficient diet, effects that may further compromise the clearance of hydrogen peroxide. These changes in catalase represent an adverse response to this dietary deficiency, and may be relevant to decreased catalase activity described in chronic renal insufficiency. Thus, a chronic prooxidant state, with features that mimic those of clinical uremia, increases DNA synthesis of renal tubular epithelium, induces mRNA expression for collagens I, III and IV in conjunction with the mRNA for the fibrogenic cytokine, TGF-beta1. Oxidants also induce collagen III, collagen IV and TGF-beta1 mRNA in vitro.

Animals↗
PubMed1998

Proximal tubular basement membrane width in insulin-dependent diabetes mellitus.

Although glomerular structure has been studied, careful evaluation of tubular basement membrane (TBM) structure in diabetes in humans has not been done. We measured proximal TBM width, glomerular basement membrane (GBM) width, mesangial fractional volume [Vv(Mes/glom)], mesangial matrix fractional volume [Vv(MM/glom)], and cortical interstitial fractional volume [Vv(Int/cortex)] in 35 insulin-dependent diabetic (IDDM) patients and 20 controls. The patients' mean age was 28 +/- 10 years (X +/- SD) and IDDM duration was 17 +/- 8 years. Twenty-five patients were normoalbuminuric, four microalbuminuric, and six had overt proteinuria. Tubular basement membrane and GBM widths were measured by the orthogonal intercept method and mesangial and interstitial parameters by point counting. The TBM width was 915 +/- 320 nm in IDDM patients and 558 +/- 116 nm in controls (P = 0.0005); the TBM width was also increased in normoalbuminuric patients (849 +/- 297 nm, P = 0.0005). The TBM width was strongly directly related to GBM width (r = 0.67, P < 0.001), Vv(Mes/glom) (r = 0.52, P < 0.01), and Vv(MM/glom) (r = 0.61, P < 0.001), but only weakly to Vv(Int/cortex) (r = 0.29, NS). The TBM width (r = 0.65, P < 0.001) and GBM width (r = 0.65, P < 0.001) were strongly related to hemoglobin A1C (HbA1C), while the Vv(Mes/glom) (r = 0.35, P < 0.05) and Vv(Int/cortex) (r = 0.30, NS) were only weakly related to HbA1C. Thus, increased proximal TBM width is an integral component of early nephropathology in IDDM patients. This study suggests that the metabolic disturbances of diabetes are strong determinants of the constellation of structural abnormalities occurring in human diabetic nephropathy.

Adolescent↗
PubMed1998

Lovastatin reduces glomerular macrophage influx and expression of monocyte chemoattractant protein-1 mRNA in nephrotic rats.

Glomerular expression of monocyte chemoattractant protein-1 (MCP-1) and subsequent glomerular macrophage infiltration may play an important role in the development of glomerulosclerosis. Previous studies have shown that lovastatin ameliorates experimental renal disease and reduces MCP-1 expression in serum-stimulated, cultured mesangial cells. We investigated the effects of lovastatin on glomerular MCP-1 expression and macrophage infiltration in rats with puromycin aminonucleoside (PA) nephrosis, an experimental model of renal disease characterized by early macrophage infiltration. Male Sprague-Dawley rats were pretreated for 5 days with either lovastatin (4 mg/kg) or vehicle. At the end of pretreatment, the lovastatin-pretreated rats received a single i.v. injection of PA (50 mg/kg) and continued to receive daily lovastatin thereafter. The vehicle-pretreated rats received i.v. injections of either PA or saline, and continued to receive daily vehicle treatment thereafter. Ten days after PA injection, the vehicle-treated PA rats showed increased (P < 0.05) serum cholesterol (359 +/- 25 mg/100 mL) and urine albumin excretion (343 +/- 95 mg/24 hr), compared with the vehicle-treated control rats (61 +/- 3 mg/100 mL and 2.5 +/- 0.6 mg/24 hr, respectively). Serum cholesterol (193 +/- 22 mg/dL) and urine albumin excretion (255 +/- 68 mg/24 hr) were less in the lovastatin-treated PA rats than in the vehicle-treated PA rats. The number of glomerular macrophages, assessed as ED-1-positive cells, per glomerular profile was increased 77% in the vehicle-treated PA rats (3.3 +/- 0.2) compared with the vehicle-treated control rats (1.8 +/- 0.2) (P < 0.05). By contrast, the number of glomerular macrophages was not elevated in the lovastatin-treated PA rats (2.3 +/- 0.2). Thus, lovastatin in vivo can attenuate glomerular macrophage infiltration. This may represent one mechanism by which lovastatin ameliorates experimental glomerular disease.

Animals↗
PubMed1998

Relationships of cell proliferation and expression of integrin subunits and type I collagen in skin fibroblasts with renal lesions in patients with IDDM.

Previous studies have shown that cultured skin fibroblasts (SFs) from insulin-dependent diabetic mellitus (IDDM) patients with diabetic nephropathy (DN) exhibit both increased proliferation and Na+/H+ antiporter activity. The present study correlated the growth rate and mRNA expression of integrin subunits, extracellular matrix molecules, and transforming growth factor-beta in cultured SFs, with the biopsy determined rate of development of DN lesions ranging from slow to rapid in nine IDDM patients. These varying rates of development of DN lesions were expressed by a mesangial expansion score as estimated by the rate of change in mesangial fraction volume per year. Cultured SF proliferation by direct cell counts positively correlated with mesangial expansion score (r = 0.65; P < 0.05). Expression of cultured SF alpha3 integrin subunit mRNA levels, as well as type I collagen mRNA (P < 0.05 for both), but not transforming growth factor-beta mRNA levels (Northern blot analysis), were also positively correlated with mesangial expansion score. We postulate that these observations of correlations between activities of cultured SFs and the rate of progression of DN lesions may be predictive of the risk to develop clinical DN in IDDM, may be in part genetically regulated, and may be of pathogenetic importance.

Adult↗
PubMed1998

Alpha-viniferin: a prostaglandin H2 synthase inhibitor from root of Carex humilis.

An inhibitor on cyclooxygenase activity of prostaglandin H2 synthase was purified from the root of Carex humilis Leyss (Cyperaceae) by a variety of column chromatographic methods. As a result of the structure analysis by FAB-mass, 1H-NMR, and 13C-NMR spectral data, the active compound was identified as (+)-alpha-viniferin, an oligomeric stilbene characterized originally from Caragana chamlagu Lamarck (Leguminosae). (+)-alpha-Viniferin exhibited a dose-dependent inhibition on cyclooxygenase activity, where 50% of inhibition (IC50) was shown at a final concentration of about 7 microM. Resveratrol, a putative building block of oligomeric stilbenes, also inhibited the cyclooxygenase activity. The inhibitory potency of (+)-alpha-viniferin was about 3- to 4-fold stronger than that of resveratrol on cyclooxygenase activity of prostaglandin H2 synthase partially purified from sheep seminal vesicles.

Animals↗
PubMed1998

Reynosin from Sassurea lappa as inhibitor on CINC-1 induction in LPS-stimulated NRK-52E cells.

An inhibitor on CINC-1 (cytokine-induced neutrophil chemoattractant-1) induction in LPS-stimulated rat kidney epithelioid NRK-52E cells was purified from the roots of Sassurea lappa Clarke, a herbal medicine used in Korean traditional prescriptions for gastric intestinal diseases by a variety of column chromatographic procedures. The inhibitor was identified as reynosin, a sesquiterpene lactone isolated and characterized previously from Ambrosia confertiflora DC., and Magnolia grandiflora L. Reynosin exhibited a dose-dependent inhibition on CINC-1 induction in LPS-stimulated NRK-52E cells, where 50% of inhibitory effect was shown at the concentration of about 1 microM.

Animals↗
PubMed1998

Cecropin A - magainin 2 hybrid peptides having potent antimicrobial activity with low hemolytic effect.

In order to obtain peptides having improved antimicrobial activity with low hemolytic effect, a hybrid peptide (CA-MA) composed from cecropin A (1-8) and magainin 2(1-12), and its analogues with amino acid substitutions were designed and synthesized. The antimicrobial activities against bacterial cells and hemolytic activities against human red blood cells were analyzed for each peptide. Secondary structures of the peptides in aqueous solution, 50% trifluoroethanol, and sodium dodecylsulfate micelles were estimated using circular dichroism spectroscopy. The increase in hydrophobicity or alpha-helicity of the peptides correlated with an increase in hemolytic activity rather than antimicrobial activity. The substitution of Leu for Ser at position 16 in CA-MA resulted in a remarkable increase in antimicrobial activity without a significant change in hemolytic activity. Furthermore, the increase in antimicrobial activity of the peptides was not always accompanied by the increase in hemolytic activity.

Amino Acid Sequence↗
PubMed1998

Molecular cloning, chromosomal localization, and expression analysis of CYRN1 and CYRN2, two human genes coding for cyritestin, a sperm protein involved in gamete interaction.

Germ cell cyritestin is a membrane-anchored protein belonging to the ADAM family of proteins. Sequencing of eight human cyritestin cDNA clones revealed that they are identical at their 5' and 3' ends but differ from each other in the length of an internal deletion, suggesting that the human cyritestin mRNA is alternatively spliced. Internal deletions that are present in some cDNA isoforms do not cause a frameshift in the C-terminal coding region. Analysis of the predicted amino acid sequences demonstrated that the human cyritestin is a polymorphic protein that could include membrane-anchored and soluble forms. Southern blot analysis and characterization of human cyritestin genomic fragments revealed that the human genome contains two copies of the cyritestin gene instead of one as in the mouse. The human CYRN1 and CYRN2 genes were assigned to the region p12-21 of chromosome 8 and q12 of chromosome 16, respectively. Northern blot and RT-PCR analyses revealed that both human genes are expressed in the testis. Amino acid sequence comparisons between cyritestin and other members of the metalloprotease-disintegrin family of proteins suggested that human and mouse cyritestin and monkey tMDCI are homologous molecules.

ADAM Proteins↗
PubMed1998

An adaptive hypothesis for the evolution of the Y chromosome.

Population geneticists remain unsure of the forces driving the evolution of Y chromosomes. Here we consider the possibility that the degeneration of the Y reflects its inability to evolve adaptively. Because the overwhelming majority of favorable mutations on a nonrecombining proto-Y suffer a zero probability of fixation, the fitness of the Y must lag far behind that of the recombining X. At some point, this disparity will grow so large that selection favors an increase in the expression of (fit) X-linked alleles and a decrease in the expression of (unfit) Y-linked alleles. Our calculations suggest that this process acts far more rapidly than hitchhiking-induced erosion of the Y and at least as rapidly as the fixation of deleterious alleles on the Y by background selection. Most important, this hypothesis can explain the evolution of Y chromosomes in taxa such as Drosophila that have very large population sizes.

Adaptation, Biological↗
PubMed1998

Persistence of microsatellite arrays in finite populations.

Given that most microsatellite arrays are of no obvious functional significance, it is natural to ask how long these sequences persist during evolution. The expected persistence time was calculated for microsatellite arrays undergoing replication slippage and random genetic drift using diffusion theory and Monte Carlo simulation. In each of the three models of replication slippage compared, copy number changes involve only single steps. In one model, the rates of addition or loss of repeat units are constant; in the other two models, they are dependent on array length in a linear or quadratic way. For all three models, it was found that persistence time of microsatellite loci increases with population size in a sublinear fashion. A heuristic argument is presented as to why this result holds true for a more general class of mutation mechanisms, including models that incorporate base substitutions in addition to replication slippage. This suggests that the approximately 30% deficiency of microsatellite loci on chromosome X (relative to autosomes) that has been well documented for several mammalian species cannot be explained by the fact that the X chromosome has a smaller effective population size than do autosomes, as has been hypothesized.

Computer Simulation↗
PubMed1998

Temperament of preterm infants at 4 months of age: maternal ratings and perceptions.

The purpose of this study was to compare temperament of preterm infants born at 34 weeks gestation or earlier with that of healthy, term infants at 4 months of age by maternal ratings and maternal perceptions and to examine the role of social support on maternal assessments of infant temperament. The mothers of preterm infants completed the Early Infancy Temperament Questionnaire (EITQ) and the Maternal Social Support Index when the child reached 4 months adjusted age. The EITQ assesses infant temperament by maternal ratings of specific infant behaviors and by mothers' global perceptions of infant temperament. Mothers of healthy term infants completed the same instruments when they brought their 4-month-old infant for a pediatric visit. Mothers rated preterm infants as having more negative mood (p = .01) and being less adaptable (p = .03) than term infants. However, mothers perceived that preterm infants were more difficult overall (p = .00001), had more negative mood (p < .005), were less regular (p = .02), and were less adaptable (p = .03). Mothers perceive preterm infant temperament to be more difficult than that of term infants and to be more difficult than is indicated by ratings of individual infant behaviors.

Adult↗
PubMed1998

Geometric effects on resistivity measurements with four-electrode probes in isotropic and anisotropic tissues.

We studied via computer simulation the effects of electrode diameter, electrode length, interelectrode spacing, and tissue size on the accuracy of measured tissue resistivities and anisotropy ratios obtained with the widely used four-electrode technique. Such measurements commonly assume an ideal situation in which the four electrodes are infinitesimally small and the tissue is semi-infinite. Our study shows that these geometric factors can significantly affect measured resistivities, particularly for anisotropic tissues. The measured anisotropy ratio is decreased by either 1) increasing the electrode diameter or length relative to the interelectrode spacing of the probe or 2) decreasing tissue size. We have provided an equation for estimating errors in the measured anisotropy ratio from the parameters of electrode and tissue geometries. The simulation findings are supported by our in vitro experimental results.

Animals↗