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Biomedical subjects

H Sone

Publications and source records attributed to H Sone.

At least 55 records · Page 3Linked to original sources
PubMed1998

Presence of dioxins in human follicular fluid: their possible stage-specific action on the development of preimplantation mouse embryos.

Examination of human follicular fluid revealed the presence of polychlorinated dibenzodioxins (PCDDs) and dibenzofurans (PCDFs) at concentrations of approximately 1 pg/ml (0.01 pg TEQ/ml). To study their possible action, two-cell mouse embryos were cultured in the presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at concentrations between 0.5 and 100 pM and evaluated at 24-h intervals for their development to the eight-cell and blastocyst stages. The percentage of eight-cell embryos exposed to TCDD at 1, 2, and 5 pM concentrations was significantly lower than that of controls. However, blastocyst formation of the surviving eight-cell embryos was accelerated, with the number of cells in the blastocysts increased in a dose-dependent manner. Findings suggest that PCDDs and PCDFs may be present in human reproductive fluid and may exert some stage-specific effects on early embryonic development.

Animals↗
PubMed1998

Metallothionein deficiency promotes mouse skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene.

To investigate a possible involvement of metallothionein (MT) in chemical carcinogenesis, MT-I and MT-II gene-deficient [MT (-/-)] transgenic mice and wild-type [MT (+/+)] control mice were topically applied at a single dose of 100, 250, 500, or 1000 microg of 7,12-dimethylbenz[a]anthracene (DMBA) on the dorsal skin and thereafter compared. After 14 weeks of DMBA treatment, the skin tumor occurred in MT (-/-) mice only and in a dose-dependent manner, whereas no change was observed in MT (+/+) mouse skin given the same DMBA treatment. The tumor cells showed proliferative activity, as shown by proliferative cell nuclear antigen staining. These results demonstrate that MT acts as an endogenous defensive factor against DMBA-induced skin tumorigenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1998

Strain differences in cytochrome P4501A1 gene expression caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat liver: role of the aryl hydrocarbon receptor and its nuclear translocator.

Rat strain variation in hepatic cytochrome P4501A1 (CYP1A1) gene expression caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was investigated along with possible underlying mechanism. TCDD at a single oral dose of 13.5 ng/kg body weight significantly increased hepatic CYP1A1 mRNA expression in DRH, Long-Evans Cinamon (LEC), Long-Evans (LE), and Holtzman (HO) rats, but not in Sprague-Dawley (SD), Wistar-Imamichi (WI), Lewis (LEW), and Fisher-344 (F344) strains. All showed significant induction of CYP1A1 mRNA at a dose of 40 ng/kg, the relative levels decreasing in the order DRH, LEC, HO, LE, F344, WI, LEW, and SD. A more than 35-fold difference in the induction of CYP1A1 RNA was evident between the DRH and SD strains. Based on CYP1A1 induction, classification into two distinctly separate groups was possible, high responders (DRH, LEC, HO, and LE) and low responders (SD, LEW, WI, and F344). The expression levels closely correlated with the steady-state aryl hydrocarbon receptor (AhR) mRNA expression, this being approximately four-fold higher in the high than in the low responder group. Analysis of the aryl hydrocarbon receptor nuclear translocator (ARNT) showed the presence of a wild type as well as an alternately spliced variant in all strains, with a 45-bp deletion whose sequence corresponded to part of 5' end of the basic region of the basic helix-loop-helix domain. Expressed levels of both products were almost equal in all the strains except DRH, LEC and HO, where the wild form predominated. The results suggest that differential expression of both AhR and ARNT are responsible for rat strain-specific differences in TCDD induced CYP1A1 expression.

Amino Acid Sequence↗
PubMed1998

Transcriptional co-regulation of Saccharomyces cerevisiae alcohol acetyltransferase gene, ATF1 and delta-9 fatty acid desaturase gene, OLE1 by unsaturated fatty acids.

The ATF1 gene encodes an alcohol acetyl transferase which catalyzes the synthesis of acetate esters from acetyl CoA and several kinds of alcohols. ATF1 expression is repressed by unsaturated fatty acids or oxygen. Analysis using ATF1-lacZ fusion plasmid revealed that ATF1 gene expression is widely repressed by a variety of unsaturated fatty acids, and the degree of ATF1 transcriptional repression varies according to the structure of the unsaturated fatty acids. Interestingly, it was noted that the degree of ATF1 transcriptional repression was related to the melting point of unsaturated fatty acids added to the medium. The OLE1 gene, which encodes delta-9 fatty acid desaturase, has been reported to be repressed by unsaturated fatty acids. Transcription of OLE1 was also repressed by a wide variety of unsaturated fatty acids under anaerobic conditions. The degree of transcriptional repression of OLE1 was also related to the melting point of the added unsaturated fatty acids. Therefore, it is considered that ATF1 and OLE1 transcription are regulated in response to cell membrane fluidity. As has been reported for OLE1, the repression of ATF1 by unsaturated fatty acids was relieved in a disruptant carrying a faa1 and faa4 double mutation, two fatty acid activation genes. However, the ATF1 transcript in this double gene disruptant was repressed by oxygen. These results suggested that ATF1 transcription was co-regulated by the same mechanism as the OLE1 gene and that unsaturated fatty acids and oxygen repressed the ATF1 transcript by a different regulation pathway.

Acetyltransferases↗
PubMed1998

Hypoxia and endothelin-1 induce VEGF production in human vascular smooth muscle cells.

Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is a secreted mitogen for vascular endothelial cells, and it promotes vascular permeability and neovascularization in vivo. We investigated the mechanisms by which low oxygen tension modulates the expression of VEGF in human aortic vascular smooth muscle cells (h-SMC) in vitro. Moreover, we measured VEGF levels in the cultured medium with or without endothelin-1 (ET-1) using a newly developed, highly sensitive, enzyme-linked immunosorbent assay. Hypoxia resulted in a substantial induction of VEGF transcripts at 3 and 24 hr. VEGF levels were significantly higher when h-SMC were cultured in medium containing ET-1 than when cultured in medium without ET-1. In conclusion, hypoxia and ET-1 constitute potent stimuli for VEGF production in h-SMC.

Cell Hypoxia↗
PubMed1998

Increase in serum vascular endothelial growth factor levels during altitude training.

The present study was performed to evaluate the effects of physical exercise at altitudes on serum vascular endothelial growth factor (VEGF) levels. Eight subjects underwent intensive swimming training for 21 days at 1886 m. After altitude training commenced, red blood cell (RBC) counts and erythropoietin levels increased, but both haemoglobin and haematocrit levels did not change significantly. The serum level of VEGF, measured by means of a highly sensitive chemiluminescence (ELISA), showed a transient decrease 10 days after start of the altitude training, thereafter increasing significantly to reach a peak level 19 days later, rising from 23.0 +/- 5.3 to 46.0 +/- 14.6 pg mL-1 (P < 0.05 vs. before). On return to low altitude in Japan, the level of VEGF decreased, and 1 month later had returned to initial levels. Endurance training at altitudes increases serum VEGF levels; this could be an adaptive reaction to hypoxic conditions. This result suggests that VEGF may provide a new physiological parameter for hypoxic stress imposed by high altitude training.

Adult↗
PubMed1998

Region of FLO1 proteins responsible for sugar recognition.

Yeast flocculation is a phenomenon which is believed to result from an interaction between a lectin-like protein and a mannose chain located on the yeast cell surface. The FLO1 gene, which encodes a cell wall protein, is considered to play an important role in yeast flocculation, which is inhibited by mannose but not by glucose (mannose-specific flocculation). A new homologue of FLO1, named Lg-FLO1, was isolated from a flocculent bottom-fermenting yeast strain in which flocculation is inhibited by both mannose and glucose (mannose/glucose-specific flocculation). In order to confirm that both FLO1 and Lg-FLO1 are involved in the yeast flocculation phenomenon, the FLO1 gene in the mannose-specific flocculation strain was replaced by the Lg-FLO1 gene. The transformant in which the Lg-FLO1 gene was incorporated showed the same flocculation phenotype as the mannose/glucose-specific flocculation strain, suggesting that the FLO1 and Lg-FLO1 genes encode mannose-specific and mannose/glucose-specific lectin-like proteins, respectively. Moreover, the sugar recognition sites for these sugars were identified by expressing chimeric FLO1 and Lg-FLO1 genes. It was found that the region from amino acid 196 to amino acid 240 of both gene products is important for flocculation phenotypes. Further mutational analysis of this region suggested that Thr-202 in the Lg-Flo1 protein and Trp-228 in the Flo1 protein are involved in sugar recognition.

Amino Acid Sequence↗
PubMed1998

Hemiacetal dehydrogenation activity of alcohol dehydrogenases in Saccharomyces cerevisiae.

Some methylotrophic yeasts produce methyl formate from methanol and formaldehyde via hemiacetal formation. We investigated Saccharomyces cerevisiae to find whether this yeast has a carboxylate ester producing pathway that proceeds via hemiacetal dehydrogenation. We confirmed that the purified alcohol dehydrogenase (Adh) protein from S. cerevisiae can catalyze the production of esters. High specific activities were observed toward the hemiacetals corresponding to the primary alcohols when ether groups were substituted for methylene groups, resulting in the formation of formate esters. Both ADH and methyl formate synthesizing activities were sharply reduced in the delta adh1 delta adh2 mutant. The ADH1 and ADH2 genes encode the major Adh proteins in S. cerevisiae. Thus, it was concluded that the S. cerevisiae Adh protein catalyzes activities for the production of certain carboxylate esters.

Acetals↗
PubMed1998

[Vascular endothelial growth factor levels in the aqueous and serum in diabetic retinopathy with or without neovascular glaucoma].

We determined the levels of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in the aqueous and serum in non-insulin dependent diabetic patients with proliferative retinopathy (n = 12) and neovascular glaucoma (n = 11). The aqueous levels of PEGF/VPF were significantly higher in both groups than in 10 diabetics without such complications. The levels were very high in patients with neovascular glaucoma, suggesting that VEGF/VPF is involved in the pathogenesis and progression of diabetic neovascular glaucoma. The serum levels were not significantly related to the presence or the stage of retinopathy. The findings suggest the possibility of treatment of neovascular glaucoma using anti- VRGF/VFP preparations.

Adult↗
PubMed1997

Ocular vascular endothelial growth factor levels in diabetic rats are elevated before observable retinal proliferative changes.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. VEGF levels in ocular tissue of 6-, 12-, 18- and 28-week-old Goto-Kakizaki (GK) rats, a well-known model of non-insulin-dependent diabetes, were evaluated by highly sensitive ELISA. VEGF concentrations in the GK rat as well as in non-diabetic Wistar rat significantly decreased from the age of 6 weeks to 18 weeks. However, although VEGF concentrations in the Wistar rat continued to fall significantly from 18 to 28 weeks of age, the levels were maintained between 18 and 28 weeks of age in GK rats. Levels were significantly different between the GK and Wistar rats at 28 weeks of age. Results of immunohistochemical studies of the eyes of Wistar and GK rats at 28 weeks of age suggest diffuse distribution of this cytokine in cells of neural origin. Weak to moderate VEGF immunoreactivity was exhibited mainly in the ganglion cell layer, inner plexiform layer and inner/outer nuclear layers in rats with and without diabetes. However, in the retinal optic nerve fiber layer, retinal pigment epithelium and choroid, strong VEGF immunoreactivity was noted only in the GK rat. In conclusion, increased VEGF production in certain ocular tissue, similar to that in humans, is observed quite early, at least before the appearance of observable retinal changes in the diabetic GK rat. This also suggests that the GK rat can be used as a model of initial or latent phase diabetic retinopathy.

Aging↗
PubMed1997

Acute effects of thromboxane dual blocker (KDI-792) on different portions of lower limb blood flow--a study using Doppler ultrasonography and laser Doppler flowmetry in type 2 diabetic patients.

The acute effects of a newly synthesized thromboxane dual blocker (KDI-792), a combined thromboxane synthase inhibitor and receptor antagonist, on lower limb circulation were examined using two-dimensional color and pulse Doppler ultrasonography and laser Doppler flowmetry. A randomized single-masked, placebo-controlled trial was performed on 36 type 2 diabetic patients with minimally impaired baseline flow. The anatomical cross-sectional area (CSA), maximum flow velocity (MFV) and flow volume index (FVI) in the right dorsal pedis artery (DPA) and right femoral artery (FA) were determined by Doppler ultrasonography before and 45 and 90 minutes after the administration of either 100 or 200 mg of KDI-792 to the dose groups or placebo to the control group. Periflux blood flow (PBF) in the right foot was determined simultaneously by laser Doppler flowmetry. Both CSA and MFV in the dose groups were significantly increased in both the FA and DPA. FVI was markedly increased from 21.4 +/- 3.7 to 68.3 +/- 26.8 in the DPA (M +/- SD, P < 0.01) and from 365.4 +/- 35.3 to 771.7 +/- 75.7 in the FA (P < 0.01) in the 200 mg dose group. In the 100 mg dose group, FVI was markedly increased from 20.0 +/- 8.7 to 68.3 +/- 26.8 (P < 0.01) in the DPA and from 372.5 +/- 130.0 to 677.5 +/- 187.8 (P < 0.01) in the FA. PBF was also increased in both dose groups (from 4.15 +/- 1.4 to 7.0 +/- 4.0 ml/min/100 g tissue in the 200 mg dose group, P < 0.01), whereas there were no significant changes in either measurement in the control group. There were no significant changes in pulse rate or blood pressure after administration in either the dosage group or the placebo group. These and previous findings indicate that a single administration of KDI-792 markedly increases lower limb blood flow and might have a more potent vasodilating effect than that of prostaglandin I2 derivatives.

Aged↗
PubMed1997

High-level expression of a sweet protein, monellin, in the food yeast Candida utilis.

We describe the heterologous expression of monellin in the yeast Candida utilis. A single-chain monellin gene was expressed under the control of the glyceraldehyde-3-phosphate dehydrogenase [correction of decarboxylase] gene promoter from C. utilis. A promoter-deficient marker gene allowed high-copy-number integration of vectors into either the rDNA locus or the URA3 gene locus. Monellin was produced at a high level, accounting for > 50% of the soluble protein. No significant decrease in the production level of monellin was detected in transformants after 50 generations of nonselective growth.

Amino Acid Sequence↗
PubMed1997

A new synthetic steroid, osaterone acetate (TZP-4238), increases cortical bone mass and strength by enhancing bone formation in ovariectomized rats.

A new synthetic steroid, 17 alpha-acetoxy-chloro-2-oxa-4,6-pregnadiene-3,20-dione (osaterone acetate, TZP-4238), has a potent antiandrogenic and gestagenic action with virtually no estrogenic and androgenic activity in their classical target organs. In the present study, the effects of TZP-4238 on the structure, strength, and turnover of the rat long bones were examined. Female Wistar rats at 12 weeks of age were ovariectomized (OVX) and treated with TZP-4238 or 17 beta-estradiol (E2) every day for 12 weeks. TZP-4238 significantly increased the diameters and maintained bone mineral density (BMD) of the femur of OVX rats. Although the BMD of the total femur was higher in E2-treated rats than that in TZP-treated rats, E2 did not increase the diameters of the femurs. To examine the effects of TZP-4238 and E2 on the BMD of different regions of the femur, the BMD was further analyzed by dividing it into 20 regions of equal longitudinal length. E2 increased the BMD of the distal and proximal metaphysis, regions rich in trabecular bone, but had no effect on the BMD of the femoral diaphysis compared with OVX control rats. In contrast, 2.5 and 12.5 mg/kg TZP-4238 increased the BMD of the femoral diaphysis, regions rich in cortical bone, but did not affect the BMD at the distal metaphysis. In agreement with the changes in the BMD of different regions of the femur, TZP-4238 but not E2 increased the physical strength of the femoral diaphysis assessed by a three-point bending test. Histomorphometric analyses of the cross-sections of the tibia revealed that TZP-4238 increased but E2 reduced the periosteal bone formation rate compared with OVX rats. In addition, TZP-4238 caused an increase in serum bone alkaline phosphatase with only a mild and transient decrease in urinary deoxypyridinoline excretion, while E2 reduced both of these parameters. These results demonstrate that TZP-4238 increases the dimension, BMD, and physical strength of the rat long bones by enhancing cortical bone formation, while estrogen maintains trabecular BMD by inhibiting bone resorption. Because the physical strength of long bones is affected by cortical bone mass and geometry, the effect of TZP-4238 on cortical bone may have a potential for the treatment of osteoporosis with reduced cortical bone formation.

Androgen Antagonists↗
PubMed1997

Biotin administration improves the impaired glucose tolerance of streptozotocin-induced diabetic Wistar rats.

The effect of biotin administration on the glucose tolerance of streptozotocin (STZ)-induced diabetic Wistar rats was investigated. STZ-induced diabetes was induced by intraperitoneal injection of streptozotocin (45 mg/kg body weight as a single dose). The impaired glucose tolerance in response to an oral glucose load (1.8g per kg body weight) in STZ-induced diabetic rats (STZ-rat) was partially improved by intraperitoneal administration of biotin for 15 days (100 micrograms/rat/day). However, a recovery in the STZ-rat's insulin secretion was not found after biotin administration. To help clarify the mechanism underlying the improvement in glucose tolerance seen with biotin treatment, glucokinase and hexokinase activities were determined in the liver and pancreas. In STZ-rats that had received biotin (STZ-biotin rats), glucokinase activity was higher by 3.4-fold in liver and by 2.4-fold in pancreas than in the STZ-rats. The biotin level of STZ-rats was significantly lower in the liver and pancreas than that of the control rats (no STZ administration); but in STZ-biotin rats, the level in these organs recovered to the control level. These results demonstrate that injected biotin can improve glucose handling without increasing insulin secretion in STZ-rats.

Animals↗
PubMed1996

Molecular cloning and analysis of the dominant flocculation gene FLO8 from Saccharomyces cerevisiae.

A flocculation gene was cloned from a Saccharomyces cerevisiae ATCC60715 genomic library, known to contain the FLO8 gene, on the basis of its ability to confer a flocculation phenotype on a nonflocculent strain. From a total of 11 130 clones, four clones sharing the several restriction fragments were isolated, suggesting that these were derived from the same locus. The results of integration mapping and disruption of the cloned gene indicated that this gene was the FLO8 gene. After disruption of the FLO8 gene, the strain lost its ability to flocculate. The DNA sequence of the FLO8 gene was determined. This gene includes a 2187-bp open reading frame that encodes a 729-amino acid protein. Computer analysis indicated that the FLO8 gene has a significant degree of homology with a S. cerevisiae chromosome V DNA sequence, but no homology with the FLO1 gene. The hydrophobicity profile of the putative FLO8 gene product did not indicate the presence of any significantly hydrophobic regions. Southern analysis of the FLO8 gene present in various yeast strains indicated that the FLO8 gene is highly conserved in yeast strains having a variety of flocculation phenotypes and genotypes. Northern analysis revealed that the level of FLO1 gene transcription is dependent on the rate of transcription of the FLO8 gene. These results suggest that the FLO8 gene mediates flocculation via transcriptional activation of the FLO1 gene.

Amino Acid Sequence↗
PubMed1996

Vascular endothelial growth factor is induced by long-term high glucose concentration and up-regulated by acute glucose deprivation in cultured bovine retinal pigmented epithelial cells.

Vascular endothelial growth factor (VEGF) is closely correlated to diabetic retinopathy. Its basal production in three types of cultured retinal cells (endothelial cells, pericytes and retinal pigment epithelial cells; RPE) was examined. RPE production of VEGF was markedly higher than the rest of the cells. VEGF production in RPE was significantly elevated by 10-day, but not by 1- or 3-day exposure to 16.5 mM glucose compared to a 5.5 mM glucose group. Transient deterioration of diabetic retinopathy is frequently observed during rapid correction of glycemic control. To determine whether VEGF is up-regulated following a sharp drop in the glucose concentration or not, we examined the changes in VEGF production in RPE before and after a sudden drop in the glucose concentration. VEGF production was significantly increased by a glucose concentration decrease from 5.5 to 0.5 mM, but not by a decrease from 33 or 16.5 to 5.5 mM. These findings suggest that up-regulation of VEGF may contribute to the development of diabetic retinopathy and its worsening by hypoglycemia.

Animals↗
PubMed1996

Copper-dependent formation of miscoding etheno-DNA adducts in the liver of Long Evans cinnamon (LEC) rats developing hereditary hepatitis and hepatocellular carcinoma.

Formation of etheno-DNA adducts in the liver was investigated in Long Evans cinnamon (LEC) rats, a Long Evans strain with hereditary abnormal copper metabolism, which develop spontaneous hepatitis and later hepatocellular carcinoma. Using an ultrasensitive immunoaffinity/32P-postlabeling assay (J. Nair et al., Carcinogenesis, 16: 613-617, 1995), the etheno adducts 1,N6-ethenodeoxyadenosine (epsilon dA) and 3,N4-ethenodeoxycytidine (epsilon dC) were measured in the liver of 7-, 18-, 30-, and 87-week-old LEC rats. Levels were highest in the liver of 18-week old rats 85 +/- 17 (epsilon dA) and 85 +/- 30 (epsilon dC) adducts per 10(9) parent nucleotides, and the increase in the levels of etheno adducts was age dependent. Age-matched Long Evans agouti rats, a tumor-free sibling line of LEC rats, had much lower levels of both etheno adducts. Etheno adduct levels in LEC rats were well correlated with the hepatic copper levels, and peak adduct levels coincided with the age of commencement of fulminant hepatitis. Our results demonstrate for the first time a copper- and age-dependent formation of highly miscoding etheno-DNA adducts in the liver of LEC rats. These adducts are formed from lipid peroxidation products (F. El-Ghissassi et al., Chem. Res. Toxicol., 8: 273-283, 1995) and thus could arise in the liver of LEC rats from oxygen radicals generated by copper-catalyzed Fenton-type reactions. Etheno-DNA adducts along with other oxidative DNA base damages may thus be involved in liver carcinogenesis in LEC rats.

Age Factors↗