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Biomedical subjects

Y B Han

Publications and source records attributed to Y B Han.

At least 19 recordsLinked to original sources
PubMed2006

Localizations of intracellular calcium and Ca2+-ATPase in hamster spermatogenic cells and spermatozoa.

Calcium plays a predominant role regulating many functional processes of spermatogenesis and fertilization. The purpose of the present study is to define the exact location of calcium as well as examine the role it plays during spermatogenesis and sperm capacitation. Testes and epididymides were obtained from adult healthy male hamsters. Spermatozoa were incubated with modified Tyrode's medium up to 4 h at 37 degrees Celsius for sperm capacitation in vitro. Samples of the testes and sperm cells were analyzed by cytochemical techniques to determine the location of calcium and Ca(2+)-ATPase and the percentage of acrosome reactions under light and electron microscopy. The data showed that (1) Sertoli cells exhibited numerous calcium precipitates as large, round, electron-dense bodies distributed throughout the cytoplasm and the mitochondrial matrix. Fine calcium precipitates existed in fewer numbers in the intracellular storage sites of spermatogonia and primary spermatocytes, in sharp distinction to secondary spermatocyte and spermatids, which showed an abundance of large and round calcium precipitates, especially in the mitochondrial matrix of spermatids. More calcium deposits were distributed in the plasma membrane (PM), acrosome membrane, and matrices of the acrosome and mitochondria following capacitation; (2) Ca(2+)-ATPase was found in the endoplasmic reticulum system and PM of noncapacitated spermatozoa as well as Sertoli cells. Capacitated spermatozoa showed a weak signal. These results suggest that the presence of calcium in spermatogenic cells might play a role in cell growth and differentiation during spermatogenesis. The Ca(2+)-ATPase function may be inhibited during capacitation, leading to an increase in acrosomal calcium level and triggering of acrosomal exocytosis.

Animals↗
PubMed2000

The trans-10,cis-12 isomer of conjugated linoleic acid downregulates stearoyl-CoA desaturase 1 gene expression in 3T3-L1 adipocytes.

Conjugated linoleic acids (CLA) are a group of positional and geometric conjugated dienoic isomers of linoleic acid. The objective of this study was to determine the effects of the cis-9,trans-11 and trans-10,cis-12 isomers of conjugated linoleic acid on lipid composition and gene expression during the differentiation of mouse 3T3-L1 preadipocytes. Treatment of differentiating 3T3-L1 preadipocytes with trans-10,cis-12 conjugated linoleic acid (CLA) resulted in a dose-dependent decrease in the expression of the stearoyl-CoA desaturase 1 gene (SCD1). The expression of other adipocyte genes such as adipose P2 (aP2), fatty acid synthase (FAS), SCD2 and the key adipogenic transcription factors, peroxisome proliferator-activated receptor gamma2 (PPARgamma2) and CCAAT enhancer binding protein alpha (C/EBPalpha), remained elevated. Cells treated with trans-10,cis-12 CLA exhibited smaller lipid droplets, with reduced levels of the major monounsaturated fatty acids, palmitoleate and oleate. By contrast, the cis-9,trans-11 isomer did not alter adipocyte gene expression. Repression of the stearoyl-CoA desaturase gene expression in adipocytes by the trans-10,cis-12 isomer may contribute to the mechanisms by which CLA reduces body fat in mice.

3T3 Cells↗
PubMed1999

Effects of water extract of 1:1 mixture of Phellodendron cortex and Aralia cortex on polyol pathway and oxidative damage in lenses of diabetic rats.

Enhanced activity of the polyol pathway and oxidative damage have been implicated in the pathogenesis of diabetic cataract. We decided to investigate whether these changes in diabetic lenses could be prevented by the water extract of Phellodendron cortex and Aralia cortex (P55A). Aldose reductase activity was inhibited significantly by the treatment with P55A. Consequently, it caused a dramatic reduction in the high sorbitol contents observed in the lenses of diabetic rats. In addition, the greatly elevated content of thiobarbituric acid reactive substances (TBARS) and carbonylated protein in diabetic rats were reduced by P55A treatment. These results suggest that P55A extract exerts an antioxidant effect by reducing lipid peroxidation and protein carbonylation as well as having an inhibitory action against aldose reductase in the lenses of diabetic rats.

Aldehyde Reductase↗
PubMed1998

The effect of genetic deficiency of adhesion molecules on the course of endotoxin-induced uveitis.

PURPOSE: Multiple adhesion molecules of the selectin, integrin, and immunoglobulin-like families are involved in the migration of leukocytes out of the bloodstream into inflamed tissues. This study addresses the question of which adhesion molecules are specifically involved in endotoxin-induced uveitis. METHODS: Mice genetically deficient in p-selectin, ICAM-1, beta2-integrin, or controls received intravitreal injections of endotoxin. Eyes were harvested 24 h later and inflammation was evaluated by histologic and immunohistochemical assays of infiltrating cells. RESULTS: Mice lacking either P-selectin or beta2-integrin had less inflammation than controls (median cells/section: 64 for P-selectin knockout vs 130 for controls, p=0.02, n=17 per group: 244 for beta2-integrin knockouts, n=14, vs 355 for controls, n=17, p=0.05). Neither gene deletion significantly changed the ratio of infiltrating neutrophils to macrophages. ICAM-1 knockouts tended to have fewer infiltrating cells (median 22 cells/section) compared to controls (median 132 cells/section), but this difference was not statistically significant (p=0.25, n=9 per group). CONCLUSIONS: P-selectin, beta2-integrin, and possibly ICAM-1 are involved in the ocular inflammatory response to endotoxin. The lack of complete inhibition of leukocyte infiltration with the complete loss of each adhesion molecule is in accord with the notion that alternative adhesion molecules also participate in this process.

Animals↗
PubMed1998

Interleukin-6 does not mediate endotoxin-induced uveitis in mice: studies in gene deletion animals.

PURPOSE: Interleukin-6 (IL-6) has been strongly implicated in anterior uveitis based on its presence in aqueous humor from infected eyes and its inflammatory effects when injected intravitreally into rats. We used IL-6-deficient mice to test further the hypothesis that IL-6 contributes to the development of endotoxin-induced uveitis. METHODS: Uveitis was scored by histologic analysis of C3H/HeN mice 24 hours after intravitreal injections of up to 200 ng of recombinant murine IL-6. Uveitis was similarly measured in IL-6-deficient mice and congenic controls 24 hours after intravitreal injection of 250 ng of Escherichia coli endotoxin. Reverse transcription-polymerase chain reaction was used to detect mRNAs for several cytokines at 3 hours postinjection. The IL-6 concentration in aqueous humor samples was determined with a bioassay using the murine B9 plasmacytoma cell line. RESULTS: Direct injection of IL-6 did not induce uveitis. Mice genetically deficient in IL-6 developed endotoxin-induced uveitis that was comparable or more severe than congenic control mice. Compensatory changes in the expression of mRNA for other cytokines were not detected in irises from the IL-6-deficient mice. In IL-6-competent mice that received bilateral endotoxin injections, no correlation was found between the number of infiltrating cells in one eye and the IL-6 concentration in the aqueous humor of the contralateral eye. CONCLUSIONS: In marked contrast to previous conclusions with rats, IL-6 was not sufficient for inducing uveitis in mice. Additionally, IL-6 was not necessary for the development of uveitis subsequent to intravitreal injection of endotoxin in mice.

Animals↗
PubMed1998

Suppression of xenobiotic-metabolizing enzyme expression in rats by acriflavine, a protein kinase C inhibitor. Effects on epoxide hydrolase, glutathione S-transferases, and cytochromes p450.

The effects of acriflavine (ACF), a protein kinase C inhibitor, on the expression of hepatic microsomal epoxide hydrolase (mEH), glutathione S-transferases (GSTs), and cytochrome P450 (P450) were assessed in rat hepatic tissue. Northern blot analysis revealed that treatment of rats with thiazole, allyl disulfide (ADS), oltipraz, or clotrimazole at a single dose of 100 mg/kg resulted in 7-18-fold increases in mEH mRNA levels at 24 hr, whereas concomitant ACF treatment (20 mg/kg, im) caused 50-95% inhibition of the chemical-induced increases in hepatic mEH mRNA levels. rGSTA2, rGSTA3, and rGSTM1 mRNA levels were also significantly suppressed at 24 hr in response to a single dose of ACF (20 mg/kg, im). Animals treated with both ACF and ADS showed complete blockage of mEH and GST gene expression as early as 12 hr after treatment. ADS-inducible increases in mEH and rGSTA2 mRNA levels were suppressed at 24 hr after treatment with ACF, in a dose-related manner, with 50% inhibitory dose (ID50) values of 2.0-2.3 mg/kg, whereas glyceraldehyde-3-phosphate dehydrogenase mRNA levels were not altered. Immunoblot analysis revealed that ACF (15 mg/kg/day, im, for 3 days) inhibited induction of mEH or rGSTA2 protein by ADS (100 mg/kg/day, po, for 3 days). The levels of hepatic P450 2B1/2, P450 2C11, and P450 3A1/2 were decreased in rats treated with ACF (15 mg/kg/day, im, for 3 days), whereas P450 1A2 and P450 2E1 expression was not affected. Treatment of rats with ACF in combination with gadolinium chloride, which inhibits mEH and GST expression through calcium channel blocking, shifted the dose-inhibitory response curves for ACF to the left, with 7-15-fold decreases in the ID50 values, indicating that the active site for ACF for suppression of mEH and GST mRNA levels differs from that for gadolinium chloride. Proflavine and safranine O, which are structurally related to ACF, also caused suppression of ADS-induced increases in mRNA levels, in a dose-dependent manner, with ID50 values of 4-9 mg/kg. These results demonstrate that ACF and its related compounds effectively suppress the expression of a battery of hepatic xenobiotic-metabolizing enzymes, including mEH, GSTs, and certain P450 forms.

Acriflavine↗
PubMed1998

Tumor necrosis factor-alpha is not essential in endotoxin induced eye inflammation: studies in cytokine receptor deficient mice.

OBJECTIVE: Anterior uveitis frequently occurs in association with specific systemic inflammatory diseases. Interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) have been implicated in the pathogenesis of these diseases. We evaluate the need for these cytokines in a model of anterior uveitis. METHODS: Endotoxin was injected into the vitreous of mice deficient in IL-1 receptor type I, TNF receptors p55 and p75, both IL-1R1 and TNFR p55, or controls. Eyes were harvested after 24 h for histology and IL-6 bioassays or after 3 h for reverse transcriptase-polymerase chain reaction analysis of mRNA for specific cytokines or enzymes. RESULTS: No significant difference in the number of infiltrating cells was found in TNFR p55/p75 deficient mice compared to controls in any of 4 separate experiments or in the combined data (p = 0.8). The number of infiltrating cells was significantly reduced in 2 of 4 experiments with IL-1R1 deficient mice (p < 0.001 based on combined data from 4 studies). IL-1R1/TNFR p55 deficient mice had a reduction in infiltrating cells in 2 of 3 experiments (p < 0.001 based on combined data from all studies). IL-6 levels were not significantly reduced in either of 2 experiments with TNFR p55/p75 deficient mice, but were reduced in one of 2 experiments with IL-1R1-/- mice (p = 0.02) and in one experiment with IL-1R1/TNFR p55 deficient mice (p = 0.01). In response to endotoxin, all 3 receptor deficient lines increased mRNA levels for IL-1-alpha, IL-10, TNF-alpha, IL-1 receptor antagonist, and inducible nitric oxide synthase. CONCLUSIONS: IL-1 appears to have a more pivotal role in endotoxin induced uveitis than TNF-alpha, although neither cytokine is essential. Deletion of receptors for both cytokines has the most consistent effect, which is in accord with the hypothesis that these cytokines are, at least in part, functionally redundant.

Animals↗
PubMed1997

Enhanced anti-tumour effects of acriflavine in combination with guanosine in mice.

The anti-tumour activity of acriflavine in combination with guanosine has been evaluated in solid or ascitic tumour-implanted animal models. Guanosine is known to potentiate the anti-tumour effects of some chemotherapeutic agents. Administration of acriflavine (15 mg kg-1 day-1, i.m., 14 days) to ICR mice subcutaneously implanted with Ehrlich carcinoma resulted in approximately 30% inhibition in tumour growth. In contrast, minor tumour growth inhibition was observed in animals treated with guanosine at the same daily dose. Treatment of animals with both acriflavine and guanosine (AG60, 1:1, w/w) at 30 mg kg-1 resulted in approximately 65% inhibition in tumour growth rate. Whereas treatment with acriflavine or guanosine resulted in 70% or 30% decrease in tumour weight, respectively, treatment of tumour-implanted mice with AG60 (30 mg kg-1) resulted in a 96% decrease in tumour weight, relative to control, 14 days after tumour-cell implantation. Dose-related inhibition in tumour growth rate was also observed in animals treated with AG60, with maximum (65%) inhibition noted at a dose of 30 mg kg-1 (ED50 23 mg kg-1). Suppression of body weight increase and elevated plasma glucose levels by acriflavine or AG60 indicated that glucose utilization might be impaired. The anti-tumour effect of AG60 was also determined in CDF1 mice intraperitoneally implanted with Ehrlich ascitic tumour. Ehrlich ascitic tumour proliferation was completely suppressed by AG60 (30 mg kg-1, i.p.). Microscopic analyses of intraperitoneal touch-prints revealed that AG60 was more effective in suppressing tumour proliferation than acriflavine alone. Fluorescent microscopic examinations demonstrated that acriflavine avidly bound with Yac-1 cell plasma membrane, leading to morphological changes in the cells, such as bleb formations, swelling and ballooning. The time-related changes in tumour cell morphology by acriflavine or AG60 might represent energy depletion, followed by osmotic lysis as a result of cationic influx. Enhanced anti-tumour activity of acriflavine in combination with guanosine might be explained by the blocking of nutrient transport through selective acriflavine binding with plasma membrane and by concomitant guanosine perturbation of cellular ATP production. This study demonstrates that guanosine enhances the anti-tumour effects of acriflavine against a variety of cancer cells without serious adverse effects, providing a preclinical basis for potential application of this combination against cancer proliferation.

Acriflavine↗
PubMed1997

A novel model of bacterially-induced acute anterior uveitis in rats and the lack of effect from HLA-B27 expression.

BACKGROUND: Humans with the major histocompatibility antigen B27 (HLA-B27) are especially at risk for developing rheumatic disorders such as ankylosing spondylitis and Reiter's syndrome. Acute anterior uveitis (AAU) often occurs in association with these diseases or in HLA B27 positive individuals without joint disease. METHODS: We induced acute anterior uveitis in Lewis rats by a standard model, the intraperitoneal injection of 200 micrograms of Escherichia coli endotoxin. We also developed a novel model of uveitis secondary to gram-negative infection. RESULTS: Transgenic rats that expressed a low copy number of the B27 gene did not differ statistically from litter mate controls in the intensity of anterior uveitis as judged by histology, enumeration of cells in aqueous humor, protein in aqueous humor, or slit lamp examination. The majority of rats exposed to live Salmonella enteritidis or Yersinia enterocolitica 0:3 using either an oral or intravenous route of infection developed anterior uveitis. In contrast to the disease induced by endotoxin that is most intense 24 hours after the endotoxin challenge, uveitis induced by live bacteria usually began 7 to 9 days after exposure to bacterial products, was more often unilateral, persisted for as long as 3 weeks, and was sometimes recurrent. The expression of HLA-B27 did not appear to influence the incidence or severity of uveitis in B27+ low copy heterozygous animals. CONCLUSION: This rat model of AAU should facilitate evaluation of bacterial antigenic component(s) involved in the pathogenesis of live gram-negative bacteria induced AAU.

Acute Disease↗
PubMed1996

Biostatic activity of Coix lacryma seed extract on Toxoplasma gondii in macrophages.

Water extract of Coix lacryma seeds (Co-Ex) was separated into several components; dissolved with Tris-Cl buffer and the supernatant (WC1), ammonium sulfate treatment supernatant (WC2) and the pellet (WC3), QAE column chromatography of WC1 and the peak portions; WC4, WC5 and WC6. Murine peritoneal macrophages in DMEM containing 10% heat-inactivated FCS were infected with tachyzoites of Toxoplasma gondii, RH strain, in vitro. By adding modulators such as Co-Ex, WC1,2,3,4,5,6 and LPS or IFN-gamma for 24 hrs, toxoplasmastatic activity of macrophages was examined in relation to nitrite production. Nitrite production of macrophages was enhanced especially in the series of WC2, WC1 and the combination sample (WC1+WC2+WC3) by order, than other components or fractions (WC4, WC5, WC6) tested. Toxoplasmastatic actions such as percentage of the macrophages infected by T. gondii and fold increase of T. gondii in macrophages showed retroverse relations with the amount of nitrite production; i.e., as nitric oxide (NO) increased the phagocytic index of macrophages and the fold increase of tachyzoites in macrophages decreased. Nitrite (NO2) production was increased by adding IFN-gamma in all cases together with enhancement of biostatic effects. Through the results obtained, it is speculated that some components other than the non-proteinous and defatted components in Coix lacryma seeds may contribute to activate macrophages through induction of NO for the biostatic activity.

Animals↗
PubMed1994

Isolation of isoguanosine from Croton tiglium and its antitumor activity.

This paper describes the isolation of isoguanosine from Croton tiglium L. and its cytotoxic effect against several tumor cell lines in culture and newly reports that isoguanosine has an antitumor activity against implanted S-180 ascitic tumor mice. Isoguanosine is effective at the dose of 24 mg/kg/day x 5, with T/C value of 168%. Isoguanosine inhibits the growth of S-180 and Ehrlich solid tumor in mice at the optimal doses of 96 mg/kg/day x 12 and 48 mg/kg/day x 12, with 1-T/C values of 65% and 60%, respectively.

Adenosine↗