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Biomedical subjects

S Goto

Publications and source records attributed to S Goto.

At least 217 records · Page 12Linked to original sources
PubMed1999

Effect of the hypocholesterolemic agent YM-16638 on cholesterol biosynthesis activity and apolipoprotein B secretion in HepG2 and monkey liver.

YM-16638 ([[5-[[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl]thio]-1,3,4-++ +thiadiazol-2-yl] thio] acetic acid) showed a strong hypocholesterolemic effect in humans and monkeys. To clarify the mechanism of this hypocholesterolemic effect, the action of YM-16638 on cholesterol biosynthesis in the cultured human hepatoma cell line HepG2 and cynomolgus monkey liver was examined. Cholesterol biosynthesis activity derived from [14C]acetic acid, [3H/14C]mevalonic acid or [14C]isopentenyl pyrophosphate substrates was significantly decreased, but not that from [3H]farnesyl pyrophosphate or [3H]squalene substrates in HepG2 cells treated with YM-16638. Simultaneously, treatment of these cells with YM-16638 changed neither the rate of apolipoprotein B synthesis from [35S]methionine nor its secretion. In addition, the activities of hepatic cholesterol biosynthesis enzymes HMG-CoA reductase, mevalonate kinase (MK), isopentenyl pyrophosphate isomerase (IPPI), farnesyl pyrophosphate synthase (FPPS), squalene synthase and squalene epoxidase were measured in monkeys fed a diet supplemented with YM-16638. Among these enzymes, MK, IPPI and FPPS activities in the YM-16638-treated group significantly decreased by 38%, 56% and 30%, respectively, when compared to those from control animals receiving no drug treatment. These results indicate that YM-16638 has the characteristics of a cholesterol biosynthesis inhibitor.

Alkyl and Aryl Transferases↗
PubMed1999

Decrease in the levels of NGF and BDNF in brains of mice fed a tryptophan-deficient diet.

The roles of dietary tryptophan (Trp) were evaluated in regulation of production of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin (NT)-3 in the various brain regions in ddY mice. Feeding the mice a Trp-deficient diet for 2 weeks significantly decreased in the hippocampal level of NGF but not those of BDNF and NT-3, as compared with feeding an adequate Trp diet. The mice fed excess Trp did not have different levels of any of these neurotrophins than in the mice fed an adequate Trp diet. The levels of BDNF in the cerebral cortex were also significantly lower in the mice fed on a Trp-deficient diet, while the levels of NGF and NT-3 in the region were not modulated upon feeding of the diet. The dietary Trp level had no significant effect on the levels of NGF, BDNF, or NT-3 in the entorhinal cortex nor septum of the mice. These results demonstrate that the brain levels of NGF and BDNF are dependent on the dietary content of tryptophan.

Alzheimer Disease↗
PubMed1999

A modified immunoperoxidase assay for detection of antibody porcine reproductive and respiratory syndrome (PRRS) virus in swine sera.

MARC-145 cell monolayers infected with PRRS virus were fixed in 3% neutral buffered formalin and embedded in paraffin. The sections were stained by avidin-biotin complex immunoperoxidase (ABC) method. Test sera were applied to sections as primary antibodies. The positive reactions were detected by ABC method and indirect immunofluorescent assay (IFA). There was good correlation between ABC and IFA, and the titers in ABC were higher than those in IFA. The present results indicate that the immunohistochemical staining is a useful test for the detection and quantitation of PRRS virus antibody in swine sera as well as IFA.

Animals↗
PubMed1999

Significance of glutathione-dependent antioxidant system in diabetes-induced embryonic malformations.

Hyperglycemia-induced embryonic malformations may be due to an increase in radical formation and depletion of intracellular glutathione (GSH) in embryonic tissues. In the past, we have investigated the role of the glutathione-dependent antioxidant system and GSH on diabetes-related embryonic malformations. Embryos from streptozotocin-induced diabetic rats on gestational day 11 showed a significantly higher frequency of embryonic malformations (neural lesions 21.5 vs. 2.8%, P<0.001; nonneural lesions 47.4 vs. 6.4%, P<0.001) and growth retardation than those of normal mothers. The formation of intracellular reactive oxygen species (ROS), estimated by flow cytometry, was increased in isolated embryonic cells of diabetic rats on gestational day 11. The concentration of intracellular GSH in embryonic tissues of diabetic pregnant rats on day 11 was significantly lower than that of normal rats. The activity of y-glutamylcysteine synthetase (gamma-GCS), the rate-limiting GSH synthesizing enzyme, in embryos of diabetic rats was significantly low, associated with reduced expression of gamma-GCS mRNA. Administration of buthionine sulfoxamine (BSO), a specific inhibitor of gamma-GCS, to diabetic rats during the period of maximal teratogenic susceptibility (days 6-11 of gestation) reduced GSH by 46.7% and increased the frequency of neural lesions (62.1 vs. 21.5%, P<0.01) and nonneural lesions (79.3 vs. 47.4%, P<0.01). Administration of GSH ester to diabetic rats restored GSH concentration in the embryos and reduced the formation of ROS, leading to normalization of neural lesions (1.9 vs. 21.5%) and improvement in nonneural lesions (26.7 vs. 47.4%) and growth retardation. Administration of insulin in another group of pregnant rats during the same period resulted in complete normalization of neural lesions (4.3 vs. 21.5%), nonneural lesions (4.3 vs. 47.4%), and growth retardation with the restoration of GSH contents. Our results indicate that GSH depletion and impaired responsiveness of GSH-synthesizing enzyme to oxidative stress during organogenesis may have important roles in the development of embryonic malformations in diabetes.

Animals↗
PubMed1999

Calcium absorption from the ingestion of coral-derived calcium by humans.

Recent dietary life involves frequent opportunities for the ingestion of purified, processed food products and preserved foods, and it has been pointed out that the current dietary mineral intake strongly tends toward nutritional imbalance. The Ryukyu Islands yield coral which contains calcium and magnesium in a content ratio of about 2 to 1, with their approximate contents of 20 and 10%, respectively. In this report, the calcium absorption from the ingestion of crackers into which the coral powder was incorporated (coral-added crackers) and that from ingestion of calcium carbonate-added crackers was comparatively assessed. Twelve healthy adult volunteers (6 men and 6 women) ingested coral-added crackers (calcium content: 525 mg) and calcium carbonate-added crackers (ditto) once each alternately on a cross-over design with a wash-out period of 3 d between the regimens. The study also included controls receiving neither cracker. The degree of intestinal absorption of calcium from coral-added crackers and that from calcium carbonate-added crackers was evaluated in terms of increment in urinary calcium excretion per dL of glomerular filtrate (GF) (difference between coral calcium and calcium carbonate) and increase in urinary calcium excretion per milligram creatinine (difference from control value). The increment in urinary calcium excretion per dL of GF during the latter half of the observation period after the ingestion of coral-added crackers was significantly greater than that during the latter half of the observation period after ingestion of calcium carbonate-added crackers (p = 0.039, paired t-test). A significant difference (from control value) in the increase of urinary calcium excretion per milligram creatinine was also observed (p = 0.0008). The present data, though from a relatively few study subjects, suggest that the calcium of coral origin is better absorbed from the intestine than calcium of calcium carbonate origin on the average.

Adult↗
PubMed1999

Comparison of various phosphate salts as the dietary phosphorus source on nephrocalcinosis and kidney function in rats.

The effects of various phosphate salts as the dietary phosphorus sources on the development of nephrocalcinosis and kidney function were examined in rats fed diets containing monophosphate salts (sodium dihydrogenphosphate, NaH2PO4, or potassium dihydrogenphosphate, KH2PO4) or polyphosphate salts (sodium tripolyphosphate, Na5P3O10, or potassium tripolyphosphate, K5P3O10), at levels representing normal phosphorus (normal phosphorus diet) or high phosphorus (high phosphorus diet) contents for 21 d. High phosphorus diet-feeding increased the kidney calcium and phosphorus concentrations. Kidney calcium and phosphorus concentrations were higher in rats fed the high phosphorus diet containing Na5P3O10 or K5P3O10 than in rats fed the high phosphorus diet containing NaH2PO4 or KH2PO4. Nephrocalcinosis was observed in all rats fed a high phosphorus diet, and the degree of nephrocalcinosis was more severe in rats fed Na5P3O10 or K5P3O10 than in rats fed NaH2PO4 or KH2PO4. In rats fed the high phosphorus diet, creatinine clearance was higher in rats fed Na5P3O10 or K5P3O10 than in rats fed NaH2PO4 or KH2PO4. In rats fed Na5P3O10 or K5P3O10, urinary albumin excretion and N-acetyl-beta-D-glucosaminidase (NAG) activity in the urine were increased in rats fed the high phosphorus diet. These were higher in rats fed the high phosphorus diet containing Na5P3O10 than in rats fed the high phosphorus diet containing NaH2PO4 or KH2PO4. This study observed that the development of nephrocalcinosis and kidney function in rats fed the high phosphorus diet was influenced by the difference in monophosphate or polyphosphate salts provided as the dietary phosphorus source, while the effects of sodium and potassium salts were not evident. We suggest that the development of nephrocalcinosis and kidney function in rats fed a high phosphorus diet was altered depending on the form of phosphate salts provided as the dietary source of phosphorus. Additionally, the development of nephrocalcinosis and diminished kidney function in rats fed the high phosphorus diet was more severe for polyphosphate salts as compared to monophosphate salts.

Acetylglucosaminidase↗
PubMed1999

[A case of keratitis, ichthyosis, and deafness syndrome with Hutchinson's triad-like symptoms].

BACKGROUND: Association of keratitis, ichthyosis, and deafness is known as KID syndrome. Only four cases have been reported in Japan by dermatologists. CASE: A male infant manifested absence of hair and generalized keratosis of the skin since birth. He had been diagnosed as having chronic mucocutaneous candidiasis (CMCC). FINDINGS: The patient manifested punctuate superficial keratopathy in the right eye and corneal opacity with peripheral neovascularization in the eye when initially seen at the age of 1 year and 4 months. The corneal lesion later developed into stromal keratitis with neovascularization in the stroma. Abnormalities simulating Hutchinson teeth were detected at the age of 4 years. Neurosensory deafness in the high-frequency region was detected at the age of 6 years. Serous tests for syphilis were consistently negative. CONCLUSION: This child is the first reported case in Japan manifesting KID syndrome with Hutchinson teeth. The associated CMCC was interpreted as due to liability to infection in patients with KID syndrome.

Deafness↗
PubMed1999

[Percutaneous transluminal septal ablation with ethanol in hypertrophic obstructive cardiomyopathy: a case report].

A 48-year-old man with hypertrophic obstructive cardiomyopathy was treated by nonsurgical septal ablation. He had previously received medical treatment using atenolol and verapamil, but severe symptoms of chest discomfort, dyspnea, and shortness of breath had persisted for 2 years. Under coronary angiography control, the first major septal branch of the anterior descending coronary artery was catheterized with a 2.0 mm coaxial percutaneous transluminal coronary angioplasty balloon catheter. After inflation of the balloon, 1.5 ml of absolute alcohol was slowly injected into the septal artery to induce a small septal infarction. The left ventricular outflow pressure gradient was decreased from 108 before to 30 mmHg after the procedure as measured by Doppler echocardiography. His chest symptom improved from New York Heart Association class III to II and left ventricular outflow gradient was maintained at 0 mmHg (at rest) at 3 months after treatment. This is a new, less invasive treatment using catheterization instead of surgical myectomy. The indication, complication, and long-term effect of the treatment must be carefully evaluated, but this is expected to become a useful method.

Angioplasty, Balloon, Coronary↗
PubMed1999

[Surgical treatment of a ruptured saccular aneurysm associated with bilateral coronary arteries-pulmonary artery fistulas: a case report].

We reported a successful operative case of ruptured coronary artery saccular aneurysm associated with bilateral coronary arteries-pulmonary artery fistulas. A 57-year-old woman, had been treated with hemodialysis due to chronic renal failure, suffered from acute heart failure with chest pain suddenly. Echocardiograph showed moderate pericardial effusion. A saccular coronary artery aneurysm with bilateral coronary arteries-pulmonary artery fistulas revealed by coronary angiogram. Ligation of coronary artery fistula, closure of orifice of draining artery to pulmonary artery and aneurysmorrhaphy were performed emergently. Post operative angiogram revealed complete disappearance of the fistulas.

Arterio-Arterial Fistula↗
PubMed1999

Heme oxygenase-2 is neuroprotective in cerebral ischemia.

Heme oxygenase (HO) is believed to be a potent antioxidant enzyme in the nervous system; it degrades heme from heme-containing proteins, giving rise to carbon monoxide, iron, and biliverdin, which is rapidly reduced to bilirubin. The first identified isoform of the enzyme, HO1, is an inducible heat-shock protein expressed in high levels in peripheral organs and barely detectable under normal conditions in the brain, whereas HO2 is constitutive and most highly concentrated in the brain. Interestingly, although HO2 is constitutively expressed, its activity can be modulated by phosphorylation. We demonstrated that bilirubin, formed from HO2, is neuroprotectant, as neurotoxicity is augmented in neuronal cultures from mice with targeted deletion of HO2 (HO2(-/-)) and reversed by low concentrations of bilirubin. We now show that neural damage following middle cerebral artery occlusion (MCAO) and reperfusion, a model of focal ischemia of vascular stroke, is substantially worsened in HO2(-/-) animals. By contrast, stroke damage is not significantly altered in HO1(-/-) mice, despite their greater debility. Neural damage following intracranial injections of N-methyl-d-aspartate (NMDA) is also accentuated in HO2(-/-) animals. These findings establish HO2 as an endogenous neuroprotective system in the brain whose pharmacologic manipulation may have therapeutic relevance.

Animals↗
PubMed1999

Genome-scale Gene Expression Analysis and Pathway Reconstruction in KEGG.

The massively parallel hybridization technologies by DNA chips and microarrays make it possible to monitor expression patterns of the whole set of genes in a genome under various conditions. The vast amount of data generated by such technologies necessitates the development of a new database management system that integrates expression data with other molecular biology databases and various analysis tools. We report here an extension of our KEGG (Kyoto Encyclopedia of Genes and Genomes) and DBGET/LinkDB systems for analyzing gene expression data in conjunction with pathway information and genomic information. It is now possible to make use of expression data for the reconstruction of pathways from the complete genome sequences.

Journal Article↗
PubMed1998

Glutathione downregulates the phosphorylation of I kappa B: autoloop regulation of the NF-kappa B-mediated expression of NF-kappa B subunits by TNF-alpha in mouse vascular endothelial cells.

Nuclear factor-kappa B (NF-kappa B) regulates gene expression upon immune and inflammatory responses. It has been demonstrated that redox regulation by thiols is involved in the signal-transduction cascade. In this study, we examined the effect of glutathione (GSH) on the NF-kappa B activity and the expression of NF-kappa B subunits induced by tumor necrosis factor-alpha (TNF-alpha) using mouse vascular endothelial cells. GSH inhibited the serine phosphorylation of I kappa B-alpha by TNF-alpha, leading to the downregulation of NF-kappa B-DNA binding activity followed by decreased expression of p65/p50 and I kappa B mRNAs. The regulation of the autoregulatory loop for the NF-kappa B activation and the expression of NF-kappa B subunits may be important in endothelial cells in response to cytokines.

Animals↗
PubMed1998

The possible effect of nitric oxide on relaxation and noradrenaline release in the isolated rabbit urethra.

We evaluated the effects of N(omega)-nitro-L-arginine (L-NNA, a nitric oxide (NO) synthase inhibitor) and carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO, a NO scavenger) on NO-mediated relaxation and noradrenaline release from adrenergic nerve endings induced by electrical field stimulation in the rabbit urethra. Electrical field stimulation caused frequency-dependent relaxation of rabbit urethral smooth muscles precontracted with phenylephrine. The relaxation responses were significantly inhibited by treatment with L-NNA or carboxy-PTIO. The inhibitory effect of carboxy-PTIO was significantly weaker than that of L-NNA. Electrical field stimulation caused significant noradrenaline release from adrenergic nerve endings in the rabbit urethra. Treatment with carboxy PTIO enhanced electrical field stimulation-induced noradrenaline release, and simultaneous application of L-NNA and carboxy-PTIO did not further enhance noradrenaline release in the rabbit urethra. As carboxy-PTIO reacts only with the free radical NO, the present results suggest that free radical NO and NO-containing compounds are involved in the L-NNA-sensitive nitrergic nerve-mediated relaxation in the rabbit urethra. At the same time free radical NO has a prejunctional action by which it may inhibit noradrenaline release from adrenergic nerves.

Animals↗
PubMed1998

Organization and structure of NADH-dependent glutamate synthase gene from rice plants.

Genomic clones for NADH-dependent glutamate synthase (NADH-GOGAT; EC 1.4.1.14) were obtained from a genomic library of rice (Oryza sativa L. cv. Sasanishki). A genomic clone (lambdaOS42, 14 kb) covered an entire structural gene and a 3.7 kb 5'-upstream region from the first methionine. Another clone (lambdaOS23, 14 kb) contained a 2.8 kb 3'-downstream region from the stop codon. A 7047 bp long clone (lambdaOSR51) consisting of full length cDNA for NADH-GOGAT was isolated from a cDNA library prepared using mRNA from roots of rice seedlings treated with 1 mM NH4Cl for 12 h. The presumed transcribed region (11.7 kb) consisted of 23 exons separated by 22 introns. Rice NADH-GOGAT is synthesized as a 2166 amino acid protein with a molecular mass of 236.7 kDa that includes a 99 amino acid presequence. DNA gel blot analysis suggested that NADH-GOGAT occurred as a single gene in rice. Primer extension experiments map the transcription start of NADH-GOGAT to identical positions. The 3. 7 kb 5'-upstream region was able to transiently express a reporter gene in cultured rice cells. Putative motifs related to the regulation of NADH-GOGAT gene expression were looked for within the 5'-upstream region by database.

Amino Acid Oxidoreductases↗
PubMed1998

Genotoxic activity of chlorinated butenoic acids in Salmonella typhimurium strains TA98, TA100 and TA104.

The mutagenic activities of several chlorinated butenoic acids, recently identified in chlorinated drinking waters, were determined by the Salmonella microsome assay. The Salmonella typhimurium tester strains TA98, TA100, and TA104 were used without S9 mix. The results from the investigation showed that (Z)-2-chloro-3-(dichloromethyl)-4-oxobutenoic acid (MX, in the open form) was the most potent mutagen of the compounds tested. However, a significant number of mutations was also induced by compounds with structural similarities to MX. In general, all the compounds, except the butenedioic acids, were mutagenic in the assays for both base-pair substitution strains (TA100, TA104) and for the frameshift strain TA98, with the highest mutagenic response observed in strain TA100. When the aldehyde group of MX and of 2-chloro-3-(chloromethyl)-4-oxobutenoic acid (CMCF, in the open form) was replaced by a dichloromethyl group, the mutagenic response in strains TA98 and TA104 changed. We concluded that a frame-shift mutation occurred because of the replacement. The increase of the TA104 mutagenicity suggested that adenosine could be the target for these types of compounds. Further evidence for such possibility were the modified adenosine adducts we could identify for some chlorinated butenoic acids.

Butyrates↗