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Biomedical subjects

K Sugimoto

Publications and source records attributed to K Sugimoto.

At least 325 records · Page 18Linked to original sources
PubMed1996

Galactosemic neuropathy in transgenic mice for human aldose reductase.

We studied the functional consequences of an enhanced polyol pathway activity, elicited with galactose feeding, on the peripheral nerve of transgenic mice expressing human aldose reductase. Nontransgenic littermate mice were used as controls. With a quantitative immunoassay, the expression level of human aldose reductase in the sciatic nerve was 791 +/- 44 ng/mg protein (mean +/- SE), about 25% of that in human sural nerve. When the transgenic mice were fed food containing 30% galactose, significant levels of galactitol accumulated in the sciatic nerve. Galactose feeding of nontransgenic littermate mice led to a 10-fold lower accumulation of galactitol. Galactose feeding for 16 weeks caused a significant and progressive decrease in motor nerve conduction velocity in transgenic mice to 80% of the level of galactose-fed littermate mice, which was not significantly different from that of galactose-free littermate mice. A morphometric analysis of sciatic nerve detected > 10% reduction of mean myelinated fiber size but no alterations of myelinated fiber density in galactose-fed transgenic mice compared with other groups. The functional and structural changes that develop in galactose-fed transgenic mice are similar to those previously reported in diabetic animals. The results of these studies suggest that transgenic mice expressing human aldose reductase may be a useful model not only for defining the role of the polyol pathway in diabetic neuropathy but also for identifying and characterizing effective inhibitors specific for human aldose reductase.

Aldehyde Reductase↗
PubMed1996

High potassium diets reduce vascular and plasma lipid peroxides in stroke-prone spontaneously hypertensive rats.

We examined the effect of high potassium (K) diet on oxidative stress to endothelium in hypertensive rats. Five-week-old stroke-prone spontaneously hypertensive rats (SHRsp) were fed a 5% high NaCl diet containing either 0.5% normal K (n = 28) or 2.1% high K (n = 19) for 6 weeks, and lipid peroxides in the aortic intima and plasma were measured. Lipid peroxides were extracted into an organic solvent to avoid the interference of carbohydrates or glycoproteins, and malondialdehyde (MDA) produced from lipid peroxides by acid-heating was measured by its reaction to thiobarbituric acid. The antioxidant butylated hydroxytoluene prevented spurious lipid peroxide formation during the whole procedure, and optimum Fe3+ allowed a maximum MDA production from lipid peroxides. The high K SHRsp showed lower lipid peroxide levels than the normal K SHRsp both in the intima (5.6 +/- 0.3 vs. 7.2 +/- 0.4 nmol MDA/mg fatty acids, p < 0.003) and plasma (0.91 +/- 0.08 vs. 1.46 +/- 0.10 nmol MDA/ml, p < 0.001). Mean arterial pressure was slightly lower by 13 mmHg in the high K SHRsp, but these differences were still obvious even when we compared groups of rats with precisely matching blood pressures. These results indicate that high K diets reduce oxidative stress on the endothelium of high NaCl-fed SHRsp independently of blood pressure changes. This effect may be involved in the mechanism by which high K diets protect endothelium and reduce stroke incidence in hypertensive animals. Thus, we improved the method of lipid peroxide measurement and propose the protective effects of high K diet against oxidative stress to endothelium in hypertension animals.

Animals↗
PubMed1996

[A patient with HCC successfully treated by ethanol injection therapy with etoposide].

A patient with hepatocellular carcinoma (HCC) who underwent successfully percutaneous ethanol injection therapy (PEIT) with etoposide was reported. A 72-year-old Japanese man with positive HCV-Ab developed multiple tumors of HCC. He underwent transcatheter arterial embolization (TAE) four times and PEIT three times, but the growth of tumors (particularly, S8) could not be controlled by these modalities. Then, the mixture of etoposide (20 mg), ethanol (8.5 ml) and lipiodol (1.5 ml) was injected into S6 tumors. Consistent with the normalization of serum AFP level, CT scan revealed the marked remaining lipiodol in these tumors. PEIT with etoposide is the treatment of choice in patients with HCC refractory to treatment by conventional TAE or PEIT.

Aged↗
PubMed1996

[A patient with hepatocellular carcinoma originating from the caudate lobe, who underwent hepatectomy following microwave coagulation therapy].

Hepatocellular carcinoma (HCC) originating from the caudate lobe is rare (about 2%), and prognosis is poor due to difficulties in early diagnosis, transarterial chemoembolization (TAE), and surgical resection. Distant metastasis is also likely to develop. To prevent metastasis during surgical manipulations, we performed microwave coagulation therapy before caudate lobectomy in one patient. Although the efficacy of this procedure remains to be elucidated, the multidisciplinary treatment described in this study is essential for the improvement of prognosis in patients with HCC developing from caudate lobe.

Carcinoma, Hepatocellular↗
PubMed1996

[A patient with pancreatic acinar cell carcinoma, effectively treated by the infusion chemotherapy through hepatic artery using 5-FU, CDDP and MMC].

Chemotherapy for pancreatic acinar cell carcinoma has not been well studied. We report herein one patient, in whom arterial chemotherapy with 5-FU, CDDP and MMC was extremely effective. He underwent distal pancreatectomy associated with partial resection of transverse colon. Hepatic recurrence was detected by MRI 8 months after the surgery. 5-FU (250 mg/day), CDDP (20 mg/day), and MMC (10 mg) was injected through a catheter introduced into the proper hepatic artery. His tumor became hardly detectable by MRI, and he was discharged about 1 month after admission. 5-FU (250 mg) and CDDP (20 mg) were injected every two weeks, and recurrence was not observed for 5 months.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

An adolescent case of anti-neutrophil cytoplasmic autoantibodies-associated crescentic glomerulonephritis complicated with subclinical autoimmune thyroiditis.

We report here a 15-year-old girl with myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA)-associated crescentic glomerulonephritis (CreGN) and subclinical autoimmune thyroiditis. She was found to have proteinuria and hematuria by a school mass-screening a year before the first visit to the hospital, where a routine examination revealed blood urea nitrogen (BUN) 36.8 mg/dl and serum creatinine concentration of 1.63 mg/dl, although she had no apparent disabilities. On admission, the additional laboratory findings showed proteinuria of 1.06 g/day, hematuria of 3+, and a creatinine clearance of 30.1 ml/min. Hypocomplementemia was not observed. A renal biopsy revealed pauci-immune CreGN with 95% fibrocellular crescents, 84% sclerosis and/or hyalinosis and a massive cellular infiltration in the interstitium. She had MPO-ANCA of 865 EU/ml and an anti-thyroid microsome antibody titer of 1:1,600 without the detection of anti-glomerular basement membrane antibodies. Laboratory tests and scintigraphies for the thyroid gland did not show any abnormalities. Under the diagnosis of MPO-ANCA-associated CreGN, cocktail therapy consisting of prednisolone, cyclophosphamide, dilazep hydrochloride and warfarin was started. Improvement of urinary abnormalities and suppression of further deterioration of renal function were observed. Serial renal biopsy 6 months after the initiation of therapy showed decrement of interstitial cell infiltration and no generation of other crescentic glomeruli. The patient's serum titer of anti-thyroid microsome antibody was not affected by the adsorption of MPO-reacted IgG, suggesting that MPO-ANCA was not cross-reactive to thyroid microsome antigen.

Adolescent↗
PubMed1995

Sequence of mouse CDC47, a member of the minichromosome maintenance (Mcm) family involved in the DNA replication licensing system.

The cDNA encoding a mouse protein, mCDC47, belonging to the minichromosome maintenance (Mcm) family possibly involved in the DNA replication licensing system, was cloned and sequenced. Its deduced amino acid (aa) sequence contained a putative DNA-dependent ATPase motif commonly observed in the family, and a zinc-finger-like domain found in some members of the family.

Adenosine Triphosphatases↗
PubMed1995

Genomic structure of the mouse gene (Lmnb1) encoding nuclear lamin B1.

The mouse gene (Lmnb1) that encodes nuclear lamin B1 was isolated. Structural analyses revealed that the lamin B1 gene spans about 43 kb of the genome and consists of 11 exons and 10 introns. Exon/intron structure of the B1 gene clearly showed the conserved organization shared among the intermediate filament protein family genes. The presumptive promoter region has high GC content and contains a CAAT box and multiple SP1 sites but no classical TATA box, suggesting that the lamin B1 gene has a typical housekeeping gene promoter with a CpG island. These data reveal the gene structure of the only remaining unanalyzed mouse somatic lamin gene. Gene structures of all the mouse somatic lamins are compared.

Amino Acid Sequence↗
PubMed1995

Dosage suppressors of the dominant G1 cyclin mutant CLN3-2: identification of a yeast gene encoding a putative RNA/ssDNA binding protein.

Three G1 cyclins, CLN1, CLN2, and CLN3, have been identified in the budding yeast Saccharomyces cerevisiae. G1 cyclins are essential, albeit functionally redundant, rate-limiting activators of cell cycle initiation. We have isolated dosage-dependent suppressor genes (designated HMD genes) of the mating defect caused by CLN3-2, a dominant mutation in CLN3, HMD2 and HMD3 are identical to STE4 and STE5, respectively, HMD1 is an essential gene that encodes a protein containing a putative RNA binding domain. Overproduction of HMD1 results in a relatively specific reduction in the level of the CLN3 or CLN3-2 transcript. This reduction occurs subsequent to transcription initiation of CLN3 since overexpression of HMD1 did not affect expression of a heterologous transcript from the CLN3 promoter but did result in a reduction of CLN3 transcript expressed from a heterologous promoter. HMD1 has at least one essential role independent of its effect on CLN3 since HMD1 remains essential for viability in the absence of a functional CLN3 gene.

Amino Acid Sequence↗
PubMed1995

Interleukin-6 inhibits the potent stimulatory action of androgens, glucocorticoids and interleukin-1 alpha on apolipoprotein D and GCDFP-15 expression in human breast cancer cells.

Our study was designed to investigate the potential interaction between steroid hormones and interleukin-6 (IL-6) in the regulation of apolipoprotein D (apo-D) and gross cystic disease fluid protein 15 (GCDFP-15) expression in ZR-75-1 human breast cancer cells. We first observed that exposure to IL-6 for 6-14 days decreased basal apo-D and GCDFP-15 secretion by 50% and 23%, respectively. In the same experiment, such treatment with IL-6 decreased cell proliferation by approximately 40% after 6 and 14 days of incubation. Exposure to IL-6 markedly decreased dihydrotestosterone (DHT)-induced apo-D and GCDFP-15 release, with a half-maximal effect measured at 13 U/ml. A similar inhibitory action of IL-6 was observed on the glucocorticoid dexamethasone (DEX)-induced apo-D and GC-DFP-15 secretion. The sensitivity of the apo-D and GCDFP-15 response to the stimulatory action of DHT or DEX was, however, not changed by concomitant exposure to IL-6. The inhibitory effect of IL-6 on the secretion of these two biochemical markers was additive to that of 17 beta-estradiol. In addition, IL-6 blocked the stimulatory effect of interleukin-1 alpha (IL-1 alpha) on apo-D and GCDFP-15 secretion. Our results show that IL-6 is a potent inhibitory of basal as well as androgen-, glucocorticoid- and IL-1 alpha-induced apo-D and GCDFP-15 secretion in ZR-75-1 human breast cancer cells, while cell proliferation is inhibited by this cytokine.

Androgens↗
PubMed1995

HYS2, an essential gene required for DNA replication in Saccharomyces cerevisiae.

To investigate cell cycle regulation at the S or G2 phase in Saccharomyces cerevisiae, we have isolated mutants displaying supersensitivity to hydroxyurea (HU), a chemical that inhibits DNA replication. Such mutants, which we have named hydroxyurea sensitive (hys), defined four linkage groups and we characterized the hys2 mutation in this study. The hys2-1 mutant displays temperature sensitive growth and a constellation of phenotypes indicating defective DNA metabolism. At the restrictive temperature, hys2-1 cells arrest as large budded cells with a single nucleus at the neck of the bud and a short spindle. The hys2-1 mutant exhibits increased rates of chromosome loss and recombination. Additionally, hys2-1 appears to accumulate incompletely replicated DNA that can be detected by a pulse field electrophoresis assay. Finally, deletion of RAD9 in a hys2-1 strain decreases the percentage of arrested cells, suggesting that an intact RAD9-checkpoint is required for the cell cycle arrest in hys2-1 cells. HYS2 encodes a 55 kDa protein that is essential for viability at all temperatures. Taken together, these data suggest that Hys2 plays a role in DNA replication.

Base Sequence↗
PubMed1995

Genome structure, mapping and expression of the tropomyosin gene tmy-1 of Caenorhabditis elegans.

The complete tropomyosin gene, designated tmy-1, of Caenorhabditis elegans was recovered by genome walking from a fragment that was obtained by exon-expression cloning using specific cloning using specific anti-tropomyosin antiserum as a probe. The genome structure of the tmy-1 gene has been determined by combining the DNA sequences of cDNA clones with those of the genomic fragments. The single-copy gene spans approximately 13 kb and include 14 exons. Comparison of cDNA and genomic sequences demonstrates that three isoforms are encoded by the gene tmy-1. Homology of the 27 C-terminal amino acid residues to those of Drosophila and vertebrates suggest that these may be the body wall, pharyngeal and non-muscle types. Tissue-specific expression of the tmy-1 gene was determined by microinjection of a promoter/lacZ fusion gene and with immunohistochemistry by using affinity-purified tissue-specific anti-tropomyosins. The 5' end promoter common to CeTMI and CeTMII is expressed in the body wall muscles, vulva, anus muscles and male tail muscles. Control sequences of the 5' end promoter are located 660 to 800 bp upstream of the initial methionine codon. The third isoform, CeTMIII, encoding 256 amino acids residues was expressed in the pharyngeal muscles by the promoter in the third intron. The mRNA of CeTMIII was trans-spliced with SL1 and SL2. These results allow is to solve the question of what is common from this worm to vertebrates, and also what are the cross-species complexities and the tissue-specific differences of tropomyosins. The tmy-1 gene is located on the C. elegans genomic YAC grid near the right end of chromosome I, in the region on the lev-11 gene.

Alternative Splicing↗
PubMed1995

Effects of nicorandil on kinetics of oxygen uptake at the onset of exercise in patients with coronary artery disease.

The beneficial effects of coronary vasodilators on exercise capacity in patients with angina pectoris are well known. However, their effects on oxygen uptake (VO2) kinetics at the onset of exercise have not been elucidated. The present study was undertaken to determine the acute effects of nicorandil, a newer coronary vasodilator, on the kinetics of VO2 at the onset of exercise in patients with ischemic heart disease. Ten patients with significant coronary stenosis performed constant mild-intensity cycle exercise (32 +/- 3 W) for 6 minutes after oral administration of 10 mg of nicorandil or an identical placebo in a double-blind, crossover manner. Nicorandil had no effect on resting heart rate, blood pressure, or VO2. However, the time constant for the increase in VO2 during constant work rate exercise was significantly shorter (the kinetics of VO2 were faster) after administration of nicorandil than after placebo (46.5 +/- 13.3 vs 51.1 +/- 11.9 seconds; p = 0.039). The increase in VO2 at 6 minutes compared with 3 minutes of constant work, which reflects the VO2 kinetics, also was reduced with nicorandil (3.8 +/- 37.9 vs 27.5 +/- 27.1 ml/min; p = 0.022). Nicorandil was found to increase the rate of VO2, increase during the onset of constant work rate exercise, probably as a result of an improved response in cardiac output. Analysis of VO2 kinetics provides new and useful parameters for the evaluation of circulatory adjustments at the onset of exercise in patients with ischemic heart disease.

Adult↗
PubMed1995

Molecular cloning of cDNA encoding mouse Cdc21 and CDC46 homologs and characterization of the products: physical interaction between P1(MCM3) and CDC46 proteins.

Two new mouse genes encoding proteins that belong to the yeast minichromosome maintenance (MCM) protein family, which is involved in the initiation of DNA replication, were isolated and their nucleotide sequence was determined. They were a putative CDC46/MCM5 homolog and a putative cdc21 homolog. About 30% amino acid identity was obtained between members in the family, and > 40% between the putative mouse and yeast homologs. The expression of these genes was cell-cycle specific at the late G1 to S phase. Immunochemical analyses showed the physical interaction between mouse P1MCM3 and CDC46 protein. These results suggest that MCM proteins function in co-ordination for DNA replication.

Animals↗