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Biomedical subjects

Y Nishio

Publications and source records attributed to Y Nishio.

At least 127 records · Page 7Linked to original sources

Chick production by in vitro fertilization of the fowl ovum.

The aim of this study was to produce viable chicks by in vitro fertilization and transfer of fertilized ova to the oviduct of recipient hens. Out of a total of 76 transferred ova, 53 were laid with fully calcified shells, 31 of which were fertile (58%). Despite the high rate of embryonic loss, six live chicks were hatched from 12 fertile ova exposed to 0.05 ml of semen (1:200 dilution). Nine healthy chicks were hatched from ten control ova which were recovered from the oviduct following artificial insemination and subsequent transfer to recipient hens. This experimental approach provides a useful model for production of transgenic chicks.

Animals↗

Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8.

Single binding sites for transcription factors NF-IL6 and NF-kappa B are present in the promoter of the interleukin (IL) 6 gene. Previous studies of internally deleted promoter mutants demonstrated that these two sites are important for the transcriptional regulation of this gene. In this report, we describe the synergistic activation of the IL-6 promoter by transcription factors NF-IL6 and NF-kappa B. Cotransfection of NF-IL6 with the NF-kappa B p65 subunit resulted in strong synergistic activation of an IL-6 promoter-reporter construct. Both the NF-IL6 and NF-kappa B binding sites in the IL-6 promoter were required for synergistic activation. Similar synergistic activation was observed in the IL-8 promoter, which also contains both NF-IL6 and NF-kappa B binding sites. Furthermore, we demonstrated that NF-IL6 and the NF-kappa B p65 subunit directly associated via the basic leucine-zipper domain of NF-IL6 and the Rel homology domain of p65. Since the promoters of many other genes involved in the inflammatory and acute-phase responses also contain binding sites for NF-IL6 and NF-kappa B, the cooperation between these two factors may have an important role in these responses. We also discuss the possible interplay between various viral gene products and these two factors in the process of viral infection and constitutive cytokine production.

Base Sequence↗

Effect of medium pH on glutathione redox cycle in cultured human umbilical vein endothelial cells.

Impairments of the glutathione redox cycle in cultured endothelial cells under acidic pH conditions were measured. Glutathione-dependent H2O2-degrading activities decreased by 20% (P < .01) at pH 6 and by 51% (P < .01) at pH 4 compared with activities at pH 7.4 1 hour after a change with fresh medium. Intracellular reduced glutathione (GSH) content increased by 85% (P < .01) following the change with pH 7.4 medium. Such increases in GSH content were impaired after exposure to acidic medium. After exposure to 500 mumol/LH2O2, intracellular GSH content decreased by 61% compared with the level obtained in the absence of H2O2 at pH 7.4 (P < .01). Compared with the level at pH 7.4, the H2O2-induced decrease in intracellular GSH content was 32% lower (P < .01) at pH 6 and did not change at all at pH 4. After exposure to 500 mumol/L H2O2, the intracellular oxidized glutathione (GSSG) content increased by 160% at pH 7.4 (P < .01), 370% at pH 6 (P < .01), and 90% at pH 4 compared with treatment without H2O2, respectively. After exposure to 500 mumol/L H2O2, the release of GSSG from cells at pH 6 decreased by 38% compared with the value found at pH 7.4 (P < .05), and the release at pH 4 completely disappeared. Both glutathione peroxidase (GPO) and glutathione reductase activities decreased as a function of a decrease in pH from 7.4 to 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Acids↗

Effects of dietary protein restriction on hemodynamics in chronic renal failure.

To elucidate the effect of protein and phosphorus restriction on hemodynamics in chronic renal failure, 14 patients were placed on a low-protein very-low-phosphorus diet (LPVLPD) and observed for metabolic and hemodynamic changes. For three weeks after initiation of the LPVLPD, the patients displayed a positive sodium balance in spite of dietary sodium restriction. During the fourth week, sodium balance decreased and approached zero. Sodium retention was accompanied by a significant decrease in plasma renin activity (P < 0.05) and mean blood pressure (P < 0.01), an increase in body weight (P < 0.05), a slight temporary decrease in hemoglobin (P < 0.05), hematocrit (P < 0.05) and total protein (P < 0.005), a negative nitrogen balance, and an increase in left ventricular ejection fraction (P < 0.01) and peak filling rate (P < 0.05). Serum creatinine concentration and endogenous creatinine clearance did not change during the experiment. These data indicate a role of dietary protein and phosphorus restriction in cardiac and fluid homeostasis in the pathophysiology of chronic renal failure.

Aged↗

NF-IL6 represses early gene expression of human papillomavirus type 16 through binding to the noncoding region.

The expression of human papillomavirus type 16 (HPV16) early genes, including E6 and E7 transforming genes, is regulated by several cellular factors binding to the noncoding region (NCR), such as the glucocorticoid receptor, NF-I, and AP1, all of which are positive regulators. We demonstrated that the nuclear factor for interleukin 6 expression (NF-IL6) specifically binds to the HPV16 NCR ranging from nucleotides 7007 to 7766 and represses the early gene expression of HPV16. The responsive element in HPV16 NCR was determined within the region ranging from nucleotides 7454 to 7766. In this region, many binding sites for other cellular transactivators, such as NF-I and AP1, have been detected. Interestingly, three of seven binding sites for NF-I and two of two binding sites for AP1 in this region overlap with the putative NF-IL6 binding sites identified by computer analysis. Competition experiments with the oligonucleotides containing such NF-I or AP1 sites indicated that NF-IL6 certainly binds to them. Furthermore, in a chloramphenicol acetyltransferase assay using mutant NF-IL6 expression vectors, the DNA binding domain of NF-IL6 was shown to be necessary for repression, whereas the functional domain was not. These findings indicate that repression may be caused by competition with other transcriptional activators, such as NF-I and AP1. Thus, NF-IL6 may play a significant role in the regulation of viral transcription as a part of the host's resistance to viral infection.

Acute-Phase Reaction↗

A nuclear factor for interleukin-6 expression (NF-IL6) and the glucocorticoid receptor synergistically activate transcription of the rat alpha 1-acid glycoprotein gene via direct protein-protein interaction.

The acute-phase reaction is accompanied by an increase in a variety of serum proteins, named acute-phase proteins. The synthesis of these proteins is synergistically controlled by glucocorticoids and inflammatory cytokines such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor alpha. Recently, we have cloned nuclear factor-IL-6 (NF-IL6), a transcription factor that activates the IL-6 gene, and have demonstrated its involvement in the expression of acute-phase-protein genes. We report here an analysis of the molecular mechanisms by which inflammatory cytokines and glucocorticoid act synergistically to activate expression of the rat alpha 1-acid glycoprotein (AGP) gene. We found that NF-IL6 and ligand-activated rat glucocorticoid receptor acted synergistically to transactivate the AGP gene and that maximal transcriptional activation of the AGP gene required expression of both intact NF-IL6 and rat glucocorticoid receptor. Surprisingly, however, transcriptional synergism was still observed even when one of the two factors lacked either its DNA-binding or transcriptional-activation function. We present evidence for a direct protein-protein interaction between these two distinct transcription factors and propose that this may be responsible for the synergistic activation of the rat AGP gene.

Acute-Phase Reaction↗

Usefulness of thallium-201 re-injection method for the evaluation of myocardial viability.

Areas of the heart which are supposedly absent of myocardial viability due to persistent thallium defect in exercise thallium myocardial scintigraphy sometimes recover ventricular wall motion through coronary revascularization. To avoid such underestimation of myocardial viability, a "re-injection method" was developed. At the peak of supine ergometer exercise in 51 patients with coronary artery disease, 111 MBq thallium was injected. Conventional exercise and 3 h-delay images were then obtained using single photon emission computed tomography. Subsequently, 55 MBq thallium was injected and a re-injection image was obtained 1 h later. Each image was divided into 12 segments and compared by left ventriculography and coronary angiography. Redistribution was found in 36 patients (71%) on the delayed images and in 44 patients (86%) on either the delayed or the re-injection images (p < 0.05). There were 127 redistribution segments (38%) on the delayed images and 163 (49%) on the re-injection images out of 336 defects on the exercise images (p < 0.001). In normokinetic segments with significant coronary stenosis and in hypokinetic segments, redistribution was found in 42% and 45% of the defects, respectively, on the delayed images, and in 65% and 62% of the defects, respectively, on the re-injection images (p < 0.01). However, no significant differences were observed between the delayed and either the delayed or re-injection images in the akinetic segments. These results suggest that the re-injection method is useful for avoiding underestimation of myocardial viability.

Aged↗

Macrophage differentiation-specific expression of NF-IL6, a transcription factor for interleukin-6.

NF-IL6 was originally identified as a DNA binding protein regulating interleukin-1 (IL-1)-stimulated IL-6 expression. Direct cloning of NF-IL6 showed its homology with C/EBP, a hepatocyte- and adipocyte-specific transcription factor. This study showed that the expression of NF-IL6 messenger RNA (mRNA) increased markedly during the differentiation to a (mRNA) increased markedly during the differentiation to a macrophage lineage in mouse myeloid leukemia cells M1, human histiocytic leukemia cells U937, promyelocytic leukemia cells HL-60, and human peripheral monocytes. Particularly in HL-60 cells that undergo granulocyte or macrophage differentiation depending on inducers, NF-IL6 mRNA was specifically upregulated during macrophage differentiation but not granulocyte differentiation. It was also shown that the functional NF-IL6 protein increased during the differentiation of U937 cells. Furthermore, recombinant NF-IL6 was found to bind to the regulatory regions of the IL-1, tumor necrosis factor, granulocyte colony-stimulating factor, and lysozyme genes, which are expressed in mature macrophages. These results suggest that NF-IL6 may possibly be involved as an important transcription factor in the process of activation and/or differentiation of macrophages.

Animals↗

Regulation of expression of the interleukin 6 gene: structure and function of the transcription factor NF-IL6.

The interleukin 6 (IL-6) promoter is rapidly and transiently activated by other cytokines, including IL-1 and tumour necrosis factor (TNF), as well as by phorbol esters and cyclic AMP agonists. Studies using promoter mutants suggested that an IL-1-responsive element mapped within the -180 to -123 region of the IL-6 promoter. A nuclear factor (NF-IL6) that recognized a unique sequence containing an inverted repeat, ACATTGCACAATCT, was identified within the region. Direct cloning of the human NF-IL6 revealed its similarity to C/EBP, a liver- and adipose tissue-specific transcription factor. C/EBP and NF-IL6 recognize the same nucleotide sequence, but exhibit distinct patterns of expression. NF-IL6 is expressed at a low level in normal tissues, but is rapidly and drastically induced by bacterial lipopolysaccharide (LPS) or inflammatory cytokines such as IL-1, TNF and IL-6. Recently, NF-IL6 has been shown to be identical to IL-6DBP, the DNA-binding protein which is responsible for IL-6-mediated induction of several acute-phase proteins. Evidence that NF-IL6 DNA-binding activity is increased after IL-6 stimulation without increased NF-IL6 protein synthesis demonstrates the importance of post-translational modification. There are some results indicating that phosphorylation is involved in transcriptional and binding activities of NF-IL6. Taken together, these findings indicate that NF-IL6 may be an important transcription factor on the signal transduction pathways of IL-1 and IL-6.

Acute-Phase Proteins↗

Phase II study of cis-diammine(glycolato)platinum, 254-S, in patients with advanced germ-cell testicular cancer, prostatic cancer, and transitional-cell carcinoma of the urinary tract. 254-S Urological Cancer Study Group.

A multicenter cooperative study was conducted to evaluate the clinical efficacy and safety of cis-diammine(glycolato)platinum (254-S), a second-generation anticancer platinum complex, in the treatment of genitourinary cancers. 254-S was given i.v. at 100 mg/m2 at 4-week intervals. As a result, 2 complete responses (CRs) and 8 partial responses (PRs) were obtained in 35 patients with transitional-cell carcinoma (TCC) of the urinary bladder or pyeloureter, 3 PRs were obtained in 16 subjects with prostatic cancer, and 6 CRs and 6 PRs were obtained in 15 patients with testicular cancer, generating objective response rates of 28.6% [95% confidence interval (CI), 14.6%-46.3%], 18.8% (95% CI, 4.0%-45.6%), and 80.0% (95% CI, 51.9%-95.7%), respectively. Bone marrow suppression was the dose-limiting toxicity, although it was reversible. Although no hydration was performed in approx. 40% of the patients, the incidence of nephrotoxic effects was low and most of those encountered were mild, the exception being one patient who showed severe renal insufficiency after the first treatment. Nausea and vomiting occurred in approx. 70% of the patients, but most gastrointestinal toxicities were controlled without antiemetic treatment. In addition, liver-function impairment was rarely observed. We conclude that 254-S is a promising cisplatin analogue for the treatment of genitourinary cancers and is worthy of further investigation in large-scale, randomized comparative studies with other platinum derivatives in both single-agent and combination regimens.

Adult↗

Some chemical properties of the HCl-methanol extract from the puparial cuticle of Drosophila melanogaster.

1. The HCl-methanol (HCl-MeOH) soluble fraction from the puparial cuticle of yellow, black and ebony of D. melanogaster was hydrolyzed in hydrochloric acid and examined for beta-alanine, ketocatechol, and acetic acid. 2. Between beta-alanine and ketocatechol and between beta-alanine and acetic acid, a quantitatively inverse relationship was found, respectively. The former relationship was further confirmed by the feeding experiment of beta-alanine to black. 3. Of total beta-alanine in the HCl-MeOH extract, the proportion of those having free amino group was 74.8 per cent. 4. All these results indicate that the HCl-MeOH soluble fraction of the puparial cuticle may be useful for investigating the cross-link structure of the cuticle.

Acetates↗

Anti-promoting effect of nordihydroguaiaretic acid on N-butyl-N-(4-hydroxybutyl)nitrosamine and sodium saccharin-induced rat urinary bladder carcinogenesis.

The effects of oral administration of nordihydroguaiaretic acid (NDGA), an antioxidant and inhibitor of arachidonic acid metabolism, on rat bladder carcinogenesis were examined. Six-week-old male Fischer 344 rats were given drinking water containing 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine for 4 weeks. Following this 4-week period, diet containing 5% sodium saccharin (SS) with or without 0.1% NDGA supplement was given to the rats for 36 weeks. The incidences of papillary or nodular (PN) hyperplasia and of papilloma in the group treated with SS plus NDGA were significantly lower than those in the group treated with SS alone. The number of PN hyperplasic foci per 10 cm of basement membrane in rats treated with SS plus NDGA was also lower than that in the group treated with SS alone. These results suggest that NDGA has an anti-tumor-promoting effect on rat bladder carcinogenesis.

Animals↗

[Prophylactic effect of UFT in combination with intravesical chemotherapy on the recurrence of superficial bladder tumor].

The influence of N1-(2-tetrahydrofuryl)-5-fluorouracil plus uracil (UFT) on the recurrence of superficial bladder tumors was evaluated in a randomized clinical study. Group A (n = 196) underwent transurethral resection (TUR) and the intravesical chemoprophylaxis, while group B (n = 193) received 400 mg per a day of UFT orally for 6 months in addition to the instillation therapy. These adjuvant therapy was started one week after TUR. Consequently, 30 patients in group B showed UFT-related toxicity and administration of UFT was discontinued in 10 of them. In addition, 87 patients in group B did not complete the 6-month course of UFT administration. Comparison of 2-year actuarial non-recurrence curves revealed no significant difference between groups A and B. However, UFT seemed to have a favorable prophylactic effect when recurrence rates were compared among those patients with recurrent tumors (generalized Wilcoxon: p = 0.1277), and those with recurrent multiple tumors (p = 0.0847).

Administration, Intravesical↗

[Pseudosarcomatous fibromyxoid tumor of the urinary bladder: a case report].

A 41-year-old man was referred to our clinic for gross hematuria. Cystoscopy revealed a 6 x 5 x 5 cm wide-based tumor located at the dome of the bladder. Pathological diagnosis of the biopsy was pseudosarcomatous fibromyxoid tumor. Microscopically this tumor was composed of spindle cells and myxoid stroma, and immunohistochemical and ultrastructural studies showed benign characteristics of this tumor. Therefore partial cystectomy was performed. It is important to recognize the histological characteristics of this essentially benign condition so that total cystectomy can be avoided.

Adult↗

[Clinicopathological analysis on invasion and metastasis in superficial bladder cancer].

We analyzed the clinico-pathological features of the initial tumors in 205 patients with superficial bladder cancer, admitted to Kyoto University Hospital between 1974 and 1988, to investigate the prognostic factors for progression to the muscle invasive disease or metastasis. Of 205 patients, 35 (17%) exhibited muscular invasion alone (12 patients) and/or metastasis (23 patients). Tumor multiplicity, higher grade and positive urinary cytology were the significant risk factors for later malignant progression. Expression of A, B, H-blood group isoantigens in the bladder tumor were significantly decreased from the onset in the patients with initially T1 tumor but not in those with Ta tumor. Significant loss of expression was also found at the time of progression in the initially Ta cases. Thus, loss of A, B, H-blood group antigen expression seems to be correlated with the malignant potential of superficial bladder cancer. However, more feasible and reliable diagnostic markers such as molecular genetical and biochemical markers remain to be developed to predict the malignant potential of the superficial bladder cancer.

ABO Blood-Group System↗

[Property of electrocardiogram gated single photon emission tomography by 99mTc-methoxy isobutyl isonitrile].

99mTc-methoxy isobutyl isonitrile (MIBI) is a new developed myocardial perfusion imaging agent. Because this compound has higher photon energy than thallium (Tl), electrocardiogram gated single photon emission tomography (SPECT): end-diastolic (ED) and end-systolic (ES) short axis (SA) images could be taken. To investigate property of gated MIBI SPECT, MIBI myocardial scintigraphy, Tl scintigraphy (TMS) and analysis of left ventricular wall motion were performed in 6 patients with myocardial infarction. Left ventricle was divided into 8 segments. Perfusion defect (PD) was scored: "0" (normal), "1" (hypo-perfusion), "2" (defect). Wall motion abnormality (WMA) was also scored: "0" (normokinesis), "1" (hypo-kinesis), "2" (a-, dys-kinesis). Severity and extent of PD and WMA were calculated. Severity of WMA was 3.0 +/- 2.0 (M +/- SD), severity of PD was 3.3 +/- 1.7 in TMS, 3.7 +/- 1.3 in no-gated MIBI, 5.0 +/- 0.6 in ES-MIBI, 7.3 +/- 2.0 in ED-MIBI. Extent of WMA was 2.3 +/- 1.0. Extent of PD was 2.5 +/- 1.3 in TMS, 3.0 +/- 1.6 in no-gated MIBI, 3.5 +/- 0.8 in ES-MIBI, 4.8 +/- 1.0 in ED-MIBI. Compared with wall motion abnormality, severity and extent of PD in ED-MIBI was larger. From our data, it is concluded that perfusion defect in ED-MIBI was overestimated significantly. When we evaluate gated MIBI image, we must consider this property.

Aged↗