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Biomedical subjects

Y B Kim

Publications and source records attributed to Y B Kim.

At least 91 records · Page 5Linked to original sources

Occurrence of aflatoxin M1 in Korean dairy products determined by ELISA and HPLC.

The occurrence of aflatoxin M1 (AFM1) in pasteurized milk and dairy products was investigated by using direct competitive enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC). The recoveries of AFM1 from the samples spiked at levels between 5 and 500 pg/ml were 88.0-106.5% for pasteurized milk and 84.0-94.0% for yoghurt by ELISA. By HPLC, the recoveries were 103-120% for pasteurized milk and 87.0-93.0% for yoghurt. The limits of detection were found to be 2 pg/ml by ELISA and 10 pg/ml by HPLC. Among a total of 180 samples collected in Seoul, Korea, the incidence of AFM1 in pasteurized milk, infant formula, powdered milk and yoghurt was 76, 85, 75, and 83%, respectively, with a mean concentration of 18, 46, 200, and 29 pg/g, respectively, when determined by ELISA. These results obtained by ELISA were closely related to those by HPLC for AFM1 (r2 = 0.9783).

Aflatoxin M1↗

A case of primary hepatic lymphoma with hepatitis C liver cirrhosis.

Primary hepatic lymphoma is rare. The usual type is a large-cell, high-grade malignant B-cell lymphoma, although T-cell types have been described. Several cases of primary hepatic lymphoma of B-cell origin developing in patients with chronic hepatitis C virus infection have been reported. Recently, new findings have raised the question of the induction of lymphoma by hepatitis C virus. However, the causal relationship between hepatitis C viral infection and primary hepatic lymphoma remains obscure. This article reports a case of histologically proven primary hepatic lymphoma of T-cell origin, which was confined to the liver, in the setting of hepatitis C liver cirrhosis. This association has not previously been reported.

Aged↗

Pandemic spread of an O3:K6 clone of Vibrio parahaemolyticus and emergence of related strains evidenced by arbitrarily primed PCR and toxRS sequence analyses.

Vibrio parahaemolyticus O3:K6 strains responsible for the increase in the number of cases of diarrhea in Calcutta, India, beginning in February 1996 and those isolated from Southeast Asian travelers beginning in 1995 were shown to belong to a unique clone characterized by possession of the tdh gene but not the trh gene and by unique arbitrarily primed PCR (AP-PCR) profiles (J. Okuda, M. Ishibashi, E. Hayakawa, T. Nishino, Y. Takeda, A. K. Mukhopadhyay, S. Garg, S. K. Bhattacharya, G. B. Nair, and M. Nishibuchi, J. Clin. Microbiol. 35:3150-3155, 1997). Evidence supporting a hypothesis that this clone emerged only recently and is spreading to many countries was obtained in this study. Of 227 strains isolated in a hospital in Bangladesh between 1977 and 1998, only 22 strains isolated between 1996 and 1998 belonged to the new O3:K6 clone (defined by the serovar, the tdh and trh typing, and AP-PCR profiles). The O3:K6 strains isolated from clinical sources in Taiwan, Laos, Japan, Thailand, Korea, and the United States between 1997 and 1998 were also shown to belong to the new O3:K6 clone. The clonality of the new O3:K6 strains was also confirmed by analysis of the toxRS sequence, which has been shown to be useful for phylogenetic analysis of the members of the genus Vibrio. The toxRS sequences of the representative strains of the new O3:K6 clone differed from those of the O3:K6 strains isolated before 1995 at least at 7 base positions within a 1,346-bp region. A new PCR method targeted to 2 of the base positions unique to the new O3:K6 clone was developed. This PCR method could clearly differentiate all 172 strains belonging to the new O3:K6 clone from other O3:K6 strains isolated earlier. One hundred sixty-six strains belonging to 28 serovars other than O3:K6 were also examined by the new PCR method. The tdh-positive and trh-lacking strains that belonged to the O4:K68 and O1:K untypeable serovars and were isolated in three countries and from international travelers beginning in 1997 gave positive results. The AP-PCR profiles of these strains were nearly identical to those of the new O3:K6 clone, and their toxRS sequences were 100% identical to that of the new O3:K6 clone. The results suggest that these strains may have diverged from the new O3:K6 clone by alteration of the O:K antigens. In conclusion, this study presents strong evidence for the first pandemicity in the history of V. parahaemolyticus and reports a novel toxRS-targeted PCR method that will be useful in epidemiological investigation of the cases associated with the current pandemic spread.

Bacterial Proteins↗

Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice.

Protein-tyrosine phosphatase 1B (PTP-1B) is a major protein-tyrosine phosphatase that has been implicated in the regulation of insulin action, as well as in other signal transduction pathways. To investigate the role of PTP-1B in vivo, we generated homozygotic PTP-1B-null mice by targeted gene disruption. PTP-1B-deficient mice have remarkably low adiposity and are protected from diet-induced obesity. Decreased adiposity is due to a marked reduction in fat cell mass without a decrease in adipocyte number. Leanness in PTP-1B-deficient mice is accompanied by increased basal metabolic rate and total energy expenditure, without marked alteration of uncoupling protein mRNA expression. In addition, insulin-stimulated whole-body glucose disposal is enhanced significantly in PTP-1B-deficient animals, as shown by hyperinsulinemic-euglycemic clamp studies. Remarkably, increased insulin sensitivity in PTP-1B-deficient mice is tissue specific, as insulin-stimulated glucose uptake is elevated in skeletal muscle, whereas adipose tissue is unaffected. Our results identify PTP-1B as a major regulator of energy balance, insulin sensitivity, and body fat stores in vivo.

Adipose Tissue↗

In vivo administration of leptin activates signal transduction directly in insulin-sensitive tissues: overlapping but distinct pathways from insulin.

To determine whether leptin signal transduction is exerted directly upon insulin-sensitive tissues in vivo, we examined the ability of iv leptin to acutely stimulate phosphorylation of STAT3, STAT1, and MAPK, and activities of PI 3-kinase and Akt, in insulin-sensitive tissues of normal rats. Both leptin (1 mg/kg iv x 3 min) and insulin (10 U/kg iv x 3 min) stimulated tyrosine phosphorylation of STAT3 5.6- to 6.0-fold and of STAT1 4.0-fold in adipose tissue. Leptin tended to increase STAT3 phosphorylation in liver and muscle. Both hormones also increased MAPK phosphorylation: leptin increased it 3.2- to 3.8-fold in adipose tissue and liver, whereas insulin stimulated MAPK phosphorylation 5.0-fold in adipose tissue, 6.8-fold in liver, and 2.5-fold in muscle. Leptin was much less effective than insulin at stimulating IRS pathways. Leptin increased IRS-1-associated PI 3-kinase activity in adipose tissue only 2.0-fold (P < 0.01) compared with the 10-fold effect of insulin. IRS-2-associated PI 3-kinase activity was increased 1.7-fold (P < 0.01) by leptin in liver and 6-fold by insulin. Akt phosphorylation and activity were not changed by leptin but increased with insulin. Lower concentrations of leptin (10 and 50 microg/kg) also stimulated STAT3 phosphorylation in fat. These effects appear to be direct because 3 min after leptin intracerebroventricular injection, phosphorylation of STAT3, STAT1, and MAPK were not stimulated in hypothalamus or adipose tissue. Furthermore, leptin activated STAT3 and MAPK in adipose tissue explants ex vivo and in 3T3-L1 adipocytes. Leptin did not activate STAT3 or MAPK in adipose tissue of db/db mice. Thus, leptin rapidly activates signaling pathways directly at the level of insulin sensitive tissues through the long-form leptin receptor, and these pathways overlap with, but are distinct from, those engaged by insulin.

3T3 Cells↗

Divergent regulation of Akt1 and Akt2 isoforms in insulin target tissues of obese Zucker rats.

To determine whether impaired Akt (protein kinase B or rac) activation contributes to insulin resistance in vivo, we examined the expression, phosphorylation, and kinase activities of Akt1 and Akt2 isoforms in insulin target tissues of insulin-resistant obese Zucker rats. In lean rats, insulin (10 U/kg i.v. x 2.5 min) stimulated Akt1 activity 6.2-, 8.8-, and 4.4-fold and Akt2 activity 5.4-, 9.3-, and 1.8-fold in muscle, liver, and adipose tissue, respectively. In obese rats, insulin-stimulated Akt1 activity decreased 30% in muscle and 21% in adipose tissue but increased 37% in liver compared with lean littermates. Insulin-stimulated Akt2 activity decreased 29% in muscle and 37% in liver but increased 24% in adipose tissue. Akt2 protein levels were reduced 56% in muscle and 35% in liver of obese rats, but Akt1 expression was unaltered. Phosphoinositide 3-kinase (PI3K) activity associated with insulin receptor substrate (IRS)-1 or phosphotyrosine was reduced 67-86% in tissues of obese rats because of lower IRS-1 protein levels and reduced insulin receptor and IRS-1 phosphorylation. In adipose tissue of obese rats, in spite of an 86% reduction in insulin-stimulated PI3K activity, activation of Akt2 was increased. Maximal insulin-stimulated (100 nmol/l) glucose transport was reduced 70% in isolated adipocytes, with a rightward shift in the insulin dose response for transport and for Akt1 stimulation but normal sensitivity for Akt2. These findings suggest that PI3K-dependent effects on glucose transport in adipocytes are not mediated primarily by Akt2. Akt1 and Akt2 activations by insulin have a similar time course and are maximal by 2.5 min in adipocytes of both lean and obese rats. We conclude that 1) activation of Akt1 and Akt2 in vivo is much less impaired than activation of PI3K in this insulin-resistant state, and 2) the mechanisms for divergent alterations in insulin action on Akt1 and Akt2 activities in tissues of insulin-resistant obese rats involve tissue- and isoform-specific changes in both expression and activation.

Adipose Tissue↗

Churg-Strauss syndrome with perforating ulcers of the colon.

We report a case of a 72-year-old woman with Churg-Strauss syndrome, who presented with intestinal perforation. She has had bronchial asthma with peripheral blood eosinophilia for 30 years. Gross findings of a resected colon showed multiple ulcers with perforation. Histologic findings demonstrated transmural inflammation infiltrated with large numbers of eosionophils, neutrophils and lymphoplasma cells, and characteristic extravascular granuloma in the subserosa. There were multifocally-distributed transmural vasculitis showing all stages of activity in medium and small-sized arteries and veins located in the submucosa, and proper muscle and subserosal layers of the colon, some of which revealed granulomatous inflammation. Histologic finding of liver showed chronic viral hepatitis B with mild inflammatory activity and macronodular cirrhosis. Immunohistochemical findings, acid fuschin orange G staining and electromicroscope found no evidence of hepatitis B virus infection contributing to the pathogenesis of this lesion.

Aged↗

Metastatic renal cell carcinoma in a meningioma: a case report.

Tumor-to-tumor metastasis is rare. We report a case of metastatic renal cell carcinoma in meningioma. A 67-year-old woman presented a two-week history of motor dysphagia and decreased short-term memory. She had undergone a left radical nephrectomy for a renal cell carcinoma 7 years ago, and had not received any adjuvant therapy. MRI disclosed a 3.0 x 3.0 x 3.0-cm sized round tentorial-based extraaxial mass with peritumoral edema in the left posterior temporal lobe. During operation, the tumor was found to be an encapsulated mass firmly attached to the tentorium. Histologically, the tumor was a meningotheliomatous meningioma extensively infiltrated by metastatic renal cell carcinoma, accompanying widespread coagulative necrosis. Immunohistochemical staining for cytokeratin revealed strong positivity only in the renal cell carcinoma component. The patient's postoperative course was uneventful. Post-operative radiation therapy was applied to the whole brain. Three months after operation, the patient developed right hemiparesis and dysphagia. Brain MRI at that time did not reveal recurrence or any other causative lesions, although the whole body scan disclosed uptake at the second lumbar vertebra and rib. The patient refused further treatment.

Aged↗

Microfracture mechanisms of composite resins containing prepolymerized particle fillers.

The effect of prepolymerized particle fillers on fracture toughness of four commercial composite resins was studied. The ground surface morphology was examined with a field emission scanning electron microscope. Fracture toughness was determined by using single edge notched specimens. Acoustic Emission (AE), which is the elastic wave due to the release of energy from the localized sources of material, was detected by sensors of a high-sensitivity and low-noise resonance type during the fracture toughness test. Acoustic Emission signals detected were analyzed for parameters such as amplitude and energy. Fracture surfaces were examined with a scanning electron microscope. The fracture toughness values, AE releasing patterns during fracture toughness test, and the fracture surface findings were analyzed to understand the fracture behavior of composite resins containing prepolymerized particle fillers. A microfracture model and fracture mechanisms to increase the fracture toughness of this type of composite resins are proposed.

Acoustics↗

Increased expression of vascular endothelial growth factor and angiogenesis in the early stage of multistep hepatocarcinogenesis.

BACKGROUND: Hepatocellular carcinoma (HCC) is known to receive its blood supply principally from the hepatic arteries. Recent studies have reported differences in the vascular supply, especially arterial supply among low- and high-grade dysplastic nodules (DNs) (also referred to as adenomatous hyperplasia and macroregenerative nodules) and HCCs. Increased expression of vascular endothelial growth factor (VEGF) has been reported in HCC. In addition, VEGF may play an important role in the early phases of hepatocarcinogenesis. METHODS: We immunohistochemically stained 7 low-grade DNs, 8 high-grade DNs, 11 early HCCs, 17 small HCCs, and 21 advanced HCCs with antibodies against VEGF, alpha-smooth muscle actin (to identify unpaired arteries, ie, arteries not accompanied by bile ducts, indicative of angiogenesis), CD34 (as a marker of sinusoidal capillarization), and proliferation cell nuclear antigen. RESULTS: Expression of VEGF was found in the hepatocytes and HCC cells. The degree of VEGF expression increased gradually according to the stepwise development of hepatocarcinogenesis. It was higher in high-grade DNs and early HCCs than in low-grade DNs. The hepatocytes and HCC cells adjacent to peliosis and fibrous septa showed stronger VEGF expression. Angiogenesis, unpaired arteries, and sinusoidal capillarization developed from low-grade DNs and gradually increased. It was highest in HCCs. The proliferation cell nuclear antigen labeling indexes of hepatocytes and HCC cells also increased gradually as hepatocarcinogenesis progressed. Small HCCs showed a higher status of neoangiogenesis and cell proliferation activity than advanced HCCs. The degree of VEGF expression was correlated with angiogenesis and cell proliferation activity. CONCLUSION: We conclude that VEGF plays a significant role in angiogenesis, growth, and development of HCC.

Carcinoma, Hepatocellular↗

Mechanism of cell cycle arrest caused by histone deacetylase inhibitors in human carcinoma cells.

Inhibitors of histone deacetylase (HDAC) block cell cycle progression at G1 in many cell types. We investigated the mechanism by which trichostatin A (TSA), a specific inhibitor of HDAC, induces G1 arrest in human cervix carcinoma HeLa cells. TSA treatment induced histone hyperacetylation followed by growth arrest in G as well as hypophosphorylation of pRb. The Cdk4 kinase activity was essentially unchanged during the TSA-induced G1 arrest. On the other hand, the arrest was accompanied by down-regulation of kinase activity of Cdk2, although the total protein levels of Cdk2 and its activator Cdc25A were unaffected. Upon TSA treatment, amounts of cyclin E and the CDK inhibitor p21WAF1/Cip1 were markedly increased, while that of cyclin A was reduced. The induction of p21 and down-regulation of cyclin A correlated well with the decreased Cdk2 activity and cell cycle arrest. Furthermore, gel filtration chromatography showed the association of p21 with the cyclin E-Cdk2 complex, suggesting that the activation of Cdk2 by the enhanced expression of cyclin E is blocked by the increased p21. The elevated expression of p2 is also observed in cells treated with trapoxin and FR901228, structurally unrelated histone deacetylase inhibitors. A human colorectal carcinoma cell line lacking both alleles of the p21 gene (p21-/-) was resistant to TSA several times more than the parental line (p21+/+). These results suggest that the suppression of Cdk2 kinase activity due to p21 overexpression play a critical role in HDAC inhibitor-induced growth inhibition.

Antibiotics, Antineoplastic↗

Diheteropeptin, a new substance with TGF-beta-like activity, produced by a fungus, Diheterospora chlamydosporia. I. Production, isolation and biological activities.

A new metabolite, diheteropeptin, was found in the culture broth of Diheterospora chlamydosporia Q58044 by screening for TGF-beta-like active substances. Diheteropeptin was extracted from the culture supernatant and purified by a series of chromatographies such as silica gel, gel filtration and HPLC. Diheteropeptin exhibited cytostatic activity in Mv1Lu cells with an IC50 value of 20.3 microM and inhibited histone deacetylase.

Anti-Bacterial Agents↗

Oxamflatin is a novel antitumor compound that inhibits mammalian histone deacetylase.

Oxamflatin [(2E)-5-[3-[(phenylsufonyl) aminol phenyl]-pent-2-en-4-ynohydroxamic acid] induces transcriptional activation of junD and morphological reversion in various NIH3T3-derived transformed cell lines. We found that oxamflatin showed in vitro antiproliferative activity against various mouse and human tumor cell lines with drastic changes in the cell morphology and in vivo antitumor activity against B16 melanoma. Oxamflatin caused an elongated cell shape with filamentous protrusions as well as arrest of the cell cycle at the G1 phase in HeLa cells. These phenotypic changes of HeLa cells were apparently similar to those by trichostatin A (TSA), a specific inhibitor of histone deacetylase (HDAC). The effect of oxamflatin on the transcriptional activity of the cytomegalovirus (CMV) promoter was examined and compared with known HDAC inhibitors, TSA, sodium n-butyrate, and FR901228. Oxamflatin as well as all these inhibitors greatly enhanced the transcriptional activity of the CMV promoter in a dose-dependent manner. Oxamflatin, like TSA, inhibited intracellular HDAC activity, as a result of which marked amounts of acetylated histone species accumulated. Finally, effects on expression of several endogenous genes involved in cell morphology and cell cycle control in HeLa cells were analysed. Expression of gelsolin, cyclin E and Cdk inhibitors including p21WAF1/Cip1 was highly augmented, while that of cyclin A and cyclin D1 was decreased by oxamflatin. These results suggest that changes in the expression pattern of the genes regulating cell morphology and the cell cycle due to histone hyperacetylation are responsible for the antitumor activity, the morphological change and the cell cycle arrest induced by oxamflatin.

Animals↗

Neuronal differentiation of neuro 2a cells by inhibitors of cell cycle progression, trichostatin A and butyrolactone I.

Trichostatin A (TSA, 17 nM), a specific and reversible inhibitor of histone deacetylase induced neurite network formation at and after 4 days. The networks were preserved for at least 3 weeks in the presence of TSA. Butyrolactone I (BLI, 23.6 microM), an inhibitor of cdc2 and cdk2 kinases, also induced neurite extension. Both compounds enhanced the acetylcholinesterase activity of the cells. Cell cycle progression of the cells was blocked by TSA (17 nM) at G1 phase alone. Furthermore, the level of histone hyperacetylation and p21(WAF1) expression in TSA-treated cells increased transiently. These findings suggest that the induction of the neuronal differentiation in Neuro 2a cells by these agents requires the cell cycle arrest at G1 phase, which is caused by inhibition of cycline dependent kinase, a target molecule of BLI and p21(WAF1).

4-Butyrolactone↗

Screening and selection of acid and bile resistant bifidobacteria.

Human fecal samples were used as a source of Bifidobacterium strains which are resistant to both acid and bile. The procedure used for screening was as follows: enrichment of Bifidobacterium strains with Bifidobacterium-selective transgalacto-oligosaccharide-propionate (TP) medium followed by acid (pH 2.0) and bile salt stressing (1.5% bile salt (w/v)). Two selected Bifidobacterium strains, designated HJ 30 and SI 31, showed considerably higher rates of survival when incubated in 50 mM phosphate buffer solution adjusted to pH 2.0 or 3.0 or in 50 mM phosphate buffer (pH 7.0) containing 0.5 or 1.0% (w/v) bile salt. HJ 30 and SI 31 were the only strains to have significant growth in Man Rogosa Sharpe (MRS) medium at 0.15% bile salt. All strains tested had similar growth rates in the absence of bile or at an initial pH value of 5.0 or 7.0 as determined by optical density measurements. For SI 31 the number of viable cell counts remained high (6 x 10(7) cfu/ml) for up to 72 h when grown in the skim milk medium, whereas all other strains examined declined to below 10(5) cfu/ml. These results demonstrate that the screening procedures developed in this study are effective for the selection of acid and bile resistant Bifidobacterium strains.

Adult↗

Effect of long-term exercise on gene expression of insulin signaling pathway intermediates in skeletal muscle.

To elucidate the molecular mechanism underlying insulin sensitivity, we have thought to investigate gene expression of insulin signaling pathway intermediates in skeletal muscle from sedentary and endurance-trained rats. Adult male Sprague-Dawley rats were trained for 9 weeks on a treadmill; 30 m/min at a 6 degrees incline, 90 min/day, 5 days/week. The levels of PI 3-kinase, GLUT4, p70 S6 kinase and Ras mRNA were significantly increased by 89, 40, 38, and 47%, respectively, with running training; however, the Nck mRNA level was decreased by 24%. mRNA levels of SHP-2, Grb2, Sos, Shc, GAP, p62 and p90 S6 kinase were unaltered by running training. We have previously reported that endurance training increases mRNA levels of insulin receptor, IRS-1 and ERK1 in skeletal muscle of rats. Taken together, our data suggest that gene expression of the insulin signal pathway intermediates is modulated by endurance training that may be associated with alteration of insulin sensitivity.

Animals↗

Early discharge after abdominal surgery: experience on a gynecologic oncology service.

OBJECTIVES: The goals of this study were to determine the length of stay (LOS) after abdominal surgery following implementation of practice guidelines on a gynecologic oncology service, to identify adverse outcomes of early discharge, and to identify clinical predictors of longer LOS. METHODS: A retrospective chart review of 266 consecutive patients who had elective abdominal surgery was performed. Clinical data, LOS, and follow-up data were abstracted. Univariate and multivariate analyses were performed to identify clinical variables predictive of LOS. RESULTS: Mean LOS was 2.94 days. Seven (2.6%) patients were readmitted after discharge. With multivariate analysis, extensive surgical procedures, coronary artery disease, and bowel surgery were predictive of longer LOS (P < 0.05). CONCLUSIONS: Early discharge following abdominal surgery was possible for most patients and was associated with a low rate of readmission. Extensive surgical procedures, coronary artery disease, and bowel surgery were predictive of longer LOS.

Abdominal Neoplasms↗