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Biomedical subjects

S Kondo

Publications and source records attributed to S Kondo.

At least 667 records · Page 37Linked to original sources
PubMed1993

Hypouricemic effect of allopurinol and the novel xanthine oxidase inhibitor TEI-6720 in chimpanzees.

The hypouricemic effect of a newly synthesized xanthine oxidase/xanthine dehydrogenase inhibitor, TEI-6720, 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid, was investigated and compared with that of allopurinol in male chimpanzees (n = 3). When allopurinol (10 mg/kg) was administered orally once a day for three consecutive days, it cumulatively reduced serum urate levels by 29.7, 50.1 and 60.2%, 24, 48 and 72 h, respectively, after the initial dose. This effect was dose dependent at doses of 3 and 10 mg/kg. At 3 mg/kg, the mean serum urate levels were 3.1, 2.4, 2.5 and 2.3 mg/dl before and 24, 48 and 72 h, respectively, after the initial dose. Animals treated with 10 mg/kg of allopurinol showed serum urate levels of 3.3, 2.3, 1.6 and 1.3 mg/dl, respectively. The urate-lowering effect of TEI-6720 was then compared with that of allopurinol at a daily dose of 5 mg/kg (n = 3). Both compounds caused striking reductions in serum and urinary uric acid levels accompanied by an increase in urinary xanthine levels. These effects of TEI-6720 were more potent than those of allopurinol. TEI-6720 reduced serum urate levels by 55.9, 69.6 and 73.6%, 24, 48 and 72 h, respectively, after the first dose, whereas the corresponding values after allopurinol were 28.1, 41.6 and 45.1%. These results suggest that the hypouricemic effect of TEI-6720 may be more potent than that of allopurinol in the treatment of hyperuricemia and gout, and that TEI-6720 may become an effective alternative drug.

Administration, Oral↗
PubMed1993

Cerebral blood flow and oxygen metabolism in progressive dementia associated with amyotrophic lateral sclerosis.

We examined regional cerebral blood flow (rCBF) and oxygen metabolism (rCMRO2) in 4 patients with progressive dementia associated with amyotrophic lateral sclerosis (ALS), in 9 patients with classical ALS without dementia, and in 13 normal controls, using positron emission tomography with oxygen-15 gas and oxygen-15 labeled carbon dioxide. The mean rCBF and rCMRO2 in the anterior cerebral hemispheres decreased significantly in patients with progressive dementia with ALS, compared to those in controls. Patients with only ALS showed very mild reductions of rCBF and rCMRO2 which were not statistically significant. These data suggest that hypoperfusion and oxygen hypometabolism in the anterior cerebral hemispheres have an etiological relationship to deterioration of intellect in patients with progressive dementia with ALS. A significant reduction in the mean rCBF was also found in the cerebellar hemispheres in progressive dementia with ALS, while a reduction of mean rCMRO2 was not significant. Remote effects analogous to crossed cerebellar diaschisis occurring bilaterally were assumed to explain the cerebellar hypoperfusion.

Adult↗
PubMed1993

Genomic binding-site cloning reveals an estrogen-responsive gene that encodes a RING finger protein.

Estrogen receptor (ER)-binding fragments were isolated from human genomic DNA by using a recombinant ER protein. Using one of these fragments as a probe, we have identified an estrogen-responsive gene that encodes a putative zinc finger protein. It has a RING finger motif present in a family of apparent DNA-binding proteins and is designated estrogen-responsive finger protein (efp). efp cDNA contains a consensus estrogen-responsive element at the 3' untranslated region that can act as a downstream estrogen-dependent enhancer. Moreover, efp is regulated by estrogen as demonstrated at both the mRNA and the protein level in ER-positive cells derived from mammary gland. These data suggest that efp may represent an estrogen-responsive transcription factor that mediates phenotypic expression of the diverse estrogen action. Thus, the genomic binding-site cloning may be applicable for isolation of the target genes of other transcription factors.

Amino Acid Sequence↗
PubMed1993

Survival of syngeneic and allogeneic grafted bone in transgenic mice.

The viability of syngeneic, allogeneic and xenogeneic bone grafts was investigated in mice and rats by the polymerase chain reaction method using carcinoembryonic antigen transgenic mice as donors. DNA of syngeneic grafts was detected more than 24 weeks after bone grafting. In contrast, the DNA of allogeneic thymic grafts and xenogeneic bone grafts disappeared by 3 weeks after transplantation. However, DNA of allogeneic bone grafts was detected until 20 weeks after transplantation. Histological examination at 12 weeks after surgery detected some donor nuclei in both syngeneic and allogeneic bone grafts.

Animals↗
PubMed1993

O-antigenic lipopolysaccharide of Vibrio cholerae O139 Bengal, a new epidemic strain for recent cholera in the Indian subcontinent.

Lipopolysaccharide (LPS) from Vibrio cholerae O139 Bengal contained colitose (3,6-dideoxy-L-galactose) in addition to glucose, L-glycero-D-manno-heptose, fructose, glucosamine and quinovosamine in its polysaccharide and only glucosamine in lipid A, while perosamine, a characteristic component sugar of V. cholerae O1 LPS, was absent. 3-Hydroxydodecanoic, tetradecanoic and hexadecanoic acids as ester-bound fatty acids and 3-hydroxytetradecanoic acid as amide-bound fatty acid were identified in the lipid A. A very high serological specificity of O139 LPS distinct from that of O1 V. cholerae was demonstrated by passive hemolysis and passive hemolysis inhibition tests by using the LPS either as antigen for sensitizing sheep red blood cells or as inhibitor in the latter test.

Carbohydrates↗
PubMed1993

Somatostatin inhibits gastrin-induced histamine secretion and synthesis in the rat.

Somatostatin is a potent inhibitor of gastric acid secretion. However, the effect of somatostatin on gastric histamine secretion and synthesis has not been well understood, despite the fact that histamine plays a key role in the regulation of gastric acid secretion. This study was designed to determine the effect of somatostatin on gastric histamine mobilization and acid secretion in conscious rats. In conscious rats with a gastric fistula, a 4 h intravenous infusion of gastrin-17 I (1 nmol/kg/h) evoked a marked increase in fundic histidine decarboxylase activity (the sole histamine-forming enzyme) and reduced fundic histamine content with a concomitant increase in gastric acid secretion. Somatostatin-14 (10 nmol/kg/h) significantly inhibited gastrin-induced gastric acid secretion and fundic histidine decarboxylase activity and prevented a gastrin-induced decrease in fundic histamine content. In conscious rats with a vesical fistula, somatostatin-14 (10 nmol/kg/h) significantly inhibited the urinary histamine excretion induced by a gastrin-17 I (1 nmol/kg/h) infusion. These findings suggest that the inhibitory action of somatostatin on gastrin-induced acid secretion is mediated by the inhibition of histamine mobilization.

Animals↗
PubMed1993

Hypouricemic effect of the novel xanthine oxidase inhibitor, TEI-6720, in rodents.

We investigated the xanthine oxidase/xanthine dehydrogenase inhibitory activity and hypouricemic effect of a newly synthesized xanthine oxidase/xanthine dehydrogenase inhibitor, TEI-6720, 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazole-carboxylic acid, and compared its effects with those of allopurinol in rodents. TEI-6720 was found to inhibit bovine milk xanthine oxidase, and mouse liver and rat liver xanthine oxidase/xanthine dehydrogenase with IC50 values of 1.4, 1.8 and 2.2 nM, respectively. On bovine milk xanthine oxidase, TEI-6720 exhibited mixed-type inhibition and the Ki value was 0.7 nM. TEI-6720 displayed prolonged urate-lowering activity in normal mice and rats. We evaluated the hypouricemic effect of TEI-6720 on hyperuricemia induced by the uricase inhibitor, potassium oxonate (250 mg/kg s.c., 1 h before the test drugs), and measured the total molarity of both serum allantoin and urate in rats. Oral TEI-6720 and allopurinol had a hypouricemic effect 2 h after their administration to oxonate-pretreated rats with ED50 values of 1.5 and 5.0 mg/kg, respectively. Both compounds also reduced the combined molarity of uric acid and allantoin in rats. The ED50 values of TEI-6720 and allopurinol were 2.1 and 6.9 mg/kg p.o., respectively. These results suggest that TEI-6720 may be useful for the treatment of hyperuricemia.

Allantoin↗
PubMed1993

Significance of vascular endothelial growth factor/vascular permeability factor for solid tumor growth, and its inhibition by the antibody.

Angiogenesis is essential for successful tumor growth in vivo. There is a hypothesis that tumors secrete a putative tumor angiogenic factor (TAF) to facilitate blood vessel formations. Although several endothelial growth factors have been reported, it remains unclear whether these factors function as TAF in vivo. Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) is a vascular endothelial mitogen that can increase blood vessel permeability. We have established a cell line (HeLa/v5), which secretes VEGF/VPF, by transfection of human VEGF/VPF cDNA. HeLa/v5 showed higher angiogenic activity, taken/planted ratio and tumor growth rate than the control transformant (HeLa/c), when they were implanted to nude mice. Administration of a polyclonal antibody, which neutralizes the mitogenic activity of VEGF/VPF in vitro, to the tumor implanted nude mice suppressed the in vivo growth of HeLa/v5. Furthermore, all 8 tumor cell lines we tested secrete VEGF/VPF into culture media. Our findings indicate that VEGF/VPF is a tumor angiogenic factor.

Animals↗
PubMed1993

N-3-hydroxypropionyl-alpha-D-perosamine homopolymer constituting the O-chain of lipopolysaccharides from Vibrio bioserogroup 1875 possessing antigenic factor(s) in common with O1 Vibrio cholerae.

A structural study was performed by 13C-n.m.r. spectroscopy and methylation analysis of the O-chain of lipopolysaccharide (LPS) from Vibrio bioserogroup 1875 possessing antigenic factor(s) in common with O1 Vibrio cholerae. It was demonstrated to contain a linear homopolymer of (1-->2)-linked N-3-hydroxypropionyl-alpha-D-perosamine [4-(3-hydroxypropanamido)-4,6-dideoxy-alpha-D-mannopyranose], which is very similar to, but not identical with, both (1-->2)-linked linear N-3-deoxy-L-glycero-tetronyl(S-2,4-dihydroxybutyryl)-alpha-D - perosamine homopolymer and (1-->2)-linked linear N-acetyl-alpha-D-perosamine homopolymer which constitute the O-chains of O1 V. cholerae and non-O1 V. cholerae bioserogroup Hakata LPS respectively.

Acetylation↗
PubMed1993

Chemical structure of the 2-keto-3-deoxyoctonate region of lipopolysaccharide isolated from Porphyromonas (Bacteroides) gingivalis.

Structural analysis of the 2-keto-3-deoxyoctonate region of lipopolysaccharide (LPS) isolated from Porphyromonas (Bacteroides) gingivalis was carried out. The substitution of the polysaccharide portion on the KDO was determined by gas chromatography/mass spectrometry of the product obtained by sequential derivatization of the LPS, including dephosphorylation, permethylation, carboxyl reduction, partial hydrolysis, carbonyl reduction, complete hydrolysis and O-acetylation. It was revealed that the KDO carries the polysaccharide on its position C5 and is phosphorylated on either position C7 or C8, although its exact position is not determined. The structure of the KDO region of P. gingivalis LPS in Gram-negative bacterial LPS had not hitherto been elucidated.

Gas Chromatography-Mass Spectrometry↗
PubMed1993

Occurrence of 2-O-methyl-N-(3-deoxy-L-glycero-tetronyl)-D-perosamine (4-amino-4,6-dideoxy-D-manno-pyranose) in lipopolysaccharide from Ogawa but not from Inaba O forms of O1 Vibrio cholerae.

A structural study by GC-MS, methylation analysis, and 1H and 13C NMR was carried out on alpha (1-->2)-linked linear N-(3-deoxy-L-glycero-tetronyl)-D-perosamine homopolymer constituting the O-polysaccharide chain of lipopolysaccharide from O1 Vibrio cholerae Ogawa and Inaba O forms. Occurrence of 2-O-methyl-N-(3-deoxy-L-glycero-tetronyl)-D-perosamine was demonstrated at the non-reducing terminus of the perosamine-homopolymer of lipopolysaccharide from the Ogawa O form in contrast to the presence of N-(3-deoxy-L-glycero-tetronyl)-D-perosamine at the nonreducing terminus for the Inaba O form.

Carbohydrate Conformation↗
PubMed1993

Location of fructose in lipopolysaccharide isolated from 01 Vibrio cholerae NIH 41R.

Fructose, a rarely occurring sugar constituent of Gram-negative bacterial lipopolysaccharides (LPS), is distributed ubiquitously in LPS of 01 Vibrio cholerae so far examined, but its location in LPS has not hitherto been elucidated. It was found that hydrazinolysis of LPS successfully affords a derivative retaining virtually all the fructose of intact LPS, but no ester-bound phosphate. Structural analysis carried out on the LPS derivative prepared by the hydrazinolysis of R-type LPS isolated from a rough mutant strain (NIH 41R) of 01 V. cholerae NIH 41 (Ogawa) revealed that the fructose is present as a non-reducing terminal residue bound to position C-6 of a glucose residue in the core region. This finding is considered to exclude the possibility that, in the LPS of 01 V. cholerae, the fructose is present in the region of the inner core in place of 2-keto-3-deoxyoctonate.

Chromatography, Gas↗
PubMed1993

Successful vitrification of bovine blastocysts, derived by in vitro maturation and fertilization.

Bovine blastocysts were produced through maturation, fertilization, and development in vitro. For vitrification, solutions designated EFS, GFS, and PFS were prepared; these were 40% ethylene glycol, 40% glycerol, and 40% propylene glycol, respectively, diluted in modified phosphate-buffered saline (PBS) containing 30% Ficoll + 0.5 M sucrose. The embryos were exposed to the solutions in one step at room temperature, kept in the solutions for various times, vitrified in liquid nitrogen, and warmed rapidly. When the embryos were vitrified in EFS solution after 1 or 2 min exposure, the postwarming survival rate, assessed by the reexpansion of the blastocoel, was 74-77%. However, when the exposure time was extended to 3 min or longer, this rate dropped to 7-0%. This reduction was attributed to the toxicity of ethylene glycol. Of the embryos vitrified in GFS solution, 53% survived when they were cooled after 1 min exposure; as the duration of the exposure increased, the survival rate increased, reaching a peak (72%) at 4 min. The rate then decreased gradually with exposure time. In PFS solution, embryos surviving after vitrification were recovered only with 1 min exposure (33%), reflecting the high toxicity of propylene glycol. After vitrification in EFS or GFS solution, two embryos were nonsurgically transferred into each of 14 recipient animals. Of the 14 recipients, ten (71%) became pregnant; two resulted in early stillbirths, four recipients delivered twins (four alive and four stillborn), and two delivered single live calves, demonstrating the effectiveness of this simple vitrification method for the cryopreservation of in-vitro-produced bovine blastocysts.

Animals↗
PubMed1993

Calcium regulating activity of 24a-homo-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 and 26,27-dimethyl-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3.

Two fluoro analogs of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], 24a-homo-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 [24aF2-homo-1,25(OH)2D3], and 26,27-dimethyl-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 [24F2-1,25(OH)2(Me)2D3] were examined for calcium (Ca)-regulating activity. The objective of the present study was to determine whether or not fluoro substitution at 24-position would alter activities of the original compounds, that is, 26,27-dimethyl 1 alpha,25-dihydroxyvitamin. D3[1,25(OH)2(Me)2D3] and 24-homo-1 alpha,25-dihydroxyvitamin D3 [24homo-1,25(OH)2D3], respectively. The relative activities of 24aF2-homo-1,25(OH)2D3, 24F2-1,25(OH)2(Me)2D3, and 1,25(OH)2D3 in competing with 1,25(OH)2D3 for binding to chick intestinal cytosol receptor were 0.28:0.5:1.0. The relative potencies of the same series of compounds in competition for the vitamin D-deficient rat serum binding sites were 0.04:0.15:1. Bone-resorbing activities of two fluoro analogs in cultures of neonatal mouse parietal bones were more potent than that of 1,25(OH)2D3. Similar results were recognized in stimulating activities of osteoclast-like cell formation. Responses of two fluoro analogs to intestinal Ca absorption were similar to that of 1,25(OH)2D3. The potencies of 1,25(OH)2D3 and its fluoro analogs in bone Ca mobilization were the highest with 1,25(OH)2D3, followed by 24F2-1,25(OH)2(Me)2D3 and 24aF2-homo-1,25(OH)2D3, in that order. From these results and the data of Paulson et al., fluoro substitution in 24-position of 1,25(OH)2D3 apparently does not alter their activities,hence, the fluoro substitution at 24-position of 1,25(OH)2D3 and the elongation of side chain of 1,25(OH)2D3 may not intensify Ca-regulating activity.

Animals↗
PubMed1993

Developmental capacity of bovine oocytes frozen in different cryoprotectants.

Iso-osmolar concentrations of 1.6 M of 1,2-propanediol, glycerol and dimethylsulfoxide were compared for their effectiveness as cryoprotectants for in vitro-matured bovine oocytes. Survival, defined as the number of morphologically normal oocytes, after freeze-thawing in 1,2-propanediol (49.8%) was significantly higher (P<0.01) than in glycerol (28.6%) or dimethylsulfoxide (32.6%). After insemination, the fertilization rate of morphologically normal oocytes frozen-thawed in 1,2-propanediol (57.9%) was higher (P<0.05) than that of those frozen in dimethylsulfoxide (38.3%). However, the proportion of surviving oocytes developing to blastocysts was not different among the 3 groups.

Journal Article↗