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T Shinohara

Publications and source records attributed to T Shinohara.

At least 19 recordsLinked to original sources
PubMed1992

Human T-cell leukemia virus type I tax transformation is associated with increased uptake of oligodeoxynucleotides in vitro and in vivo.

We have utilized antisense oligodeoxynucleotides (ODNs) to modulate transcriptional activation by the human T-cell leukemia virus type I (HTLV-I) tax gene, the major transcriptional regulator of this virus. 3'-Terminal phosphorothioate-modified antisense ODNs were shown to efficiently inhibit Tax protein expression both in vitro and in vivo. Terminal substitution did not affect the affinity of ODNs for their target sequence but conferred a 9-fold increase in tax inhibition in vitro. When delivered into mice by intraperitoneal injection, ODNs inhibited tax expression in established tumors by 90%. Unmanipulated tax-transformed mouse fibroblasts, or HTLV-I-transformed human lymphocytes, showed at least 5-fold higher ODN binding and uptake over control cells. Balb/3T3 cell binding was induced to similar levels by cellular activators. This suggests that constitutive activation by tax transformation may increase susceptibility of HTLV-I-transformed cells to antisense therapy, providing a rationale for the use of antisense ODN therapeutics in HTLV-I-associated diseases.

3T3 Cells↗
PubMed1992

Ablation of transplanted HTLV-I Tax-transformed tumors in mice by antisense inhibition of NF-kappa B.

Mice transgenic for the human T cell leukemia virus (HTLV-I) Tax gene develop fibroblastic tumors that express NF-kappa B-inducible early genes. In vitro inhibition of NF-kappa B expression by antisense oligodeoxynucleotides (ODNs) inhibited growth of these culture-adapted Tax-transformed fibroblasts as well as an HTLV-I-transformed human lymphocyte line. In contrast, antisense inhibition of Tax itself had no apparent effect on cell growth. Mice treated with antisense to NF-kappa B ODNs showed rapid regression of transplanted fibrosarcomas. This suggests that NF-kappa B expression may be necessary for the maintenance of the malignant phenotype and provides a therapeutic approach for HTLV-I-associated disease.

3T3 Cells↗
PubMed1992

Development of MEKA (phosducin), G beta, G gamma and S-antigen in the rat pineal gland and retina.

Pinealocytes and retinal photoreceptor cells contain an unusual cytoplasmic complex composed of the G beta gamma dimer of GTP-binding regulatory proteins (G-proteins) tightly bound to an acidic 33 kDa phosphoprotein termed MEKA or phosducin; MEKA is a substrate of cyclic AMP-dependent protein kinase. This study characterized the developmental appearance of these and two related proteins, G gamma and S-antigen, in pineal and retinal tissue. MEKA was absent in the pineal gland prior to birth, at a time when it was possible to detect G beta in pineal cytoplasm, indicating that the appearance of G beta in the cytoplasm precedes that of MEKA and does not appear to require the presence of MEKA. The absence of MEKA at this time indicates that the cyclic AMP stimulation of pineal serotonin N-acetyltransferase activity is not mediated by MEKA, which has been considered as a possible role of MEKA. After postnatal day 7, pineal MEKA and cytoplasmic G beta increased in a parallel manner, with peak values occurring at about postnatal day 21. Thereafter, both proteins in the pineal gland decreased in a parallel fashion to 10 and 35% of their peak values, respectively; in contrast, the cytoplasmic protein S-antigen and membrane associated G beta remained at maximal levels after this time. Whereas both MEKA and G beta decreased late in development in the pineal gland, these proteins either increased or remained constant in the retina. These tissue-specific patterns were found to differ from those of another cytosolic protein found exclusively in the pineal gland and retina, S-antigen, which remained constant after day 21 in the pineal gland but decreased in the retina late in life.

Aging↗
PubMed1992

Detection of human papillomavirus DNA in carcinomas of the nasal cavities and paranasal sinuses by polymerase chain reaction.

The authors retrospectively searched for human papillomavirus (HPV) types 16 and 18 in 60 cases of carcinoma arising from the nasal cavities (NC) and paranasal sinuses (PS) by using the polymerase chain reaction (PCR) on DNA extracted from formalin-fixed, paraffin-embedded tissues. In cases of SCC (n = 49), the authors also compared the clinical features of patients with HPV-positive and HPV-negative results to determine the clinical significance of HPV. HPV 16 and 18 were detected in 7 of the 49 cases (14%) of SCC. In the other histologic types of carcinoma (n = 11), neither HPV 16 nor HPV 18 was detected. No significant differences in the clinical features were observed between patients with SCC with HPV-positive and HPV-negative results. The results suggest that HPV 16 and 18 are implicated in the pathogenesis of SCC arising from the NC and PS. However, the presence of HPV is not related to local progression, occurrence of metastases, or the prognosis of the patients.

Adult↗
PubMed1992

Clinical significance of the epidermal growth factor receptor gene in squamous cell carcinomas of the nasal cavities and paranasal sinuses.

The authors retrospectively analyzed epidermal growth factor receptor (EGFR) gene amplification in 49 cases of squamous cell carcinoma (SCC) arising from the nasal cavities (NC) and paranasal sinuses (PS) by using slot-blot analysis of DNA extracted from formalin-fixed, paraffin-embedded tissues. Also, the relationship between the results of gene analysis and the clinical features of the patients was studied to investigate the clinical significance of the EGFR in SCC of the NC and PS. Amplification of the EGFR gene was detected in 5 of the 49 cases (10%). No significant difference was observed between EGFR gene amplification and the presence of lymph node metastases, local recurrence, or prognosis. This suggests that EGFR gene amplification is not related to the local progression or metastasis of the SCC in the NC and PS. In addition, it appears that amplification of the EGFR gene is not a prognostic indicator for SCC in the NC and PS.

Adult↗
PubMed1992

Local cerebral blood flow and its response to intravenous levodopa in progressive supranuclear palsy. Comparison with Parkinson's disease.

The local cerebral blood flow (LCBF) at steady state and after the intravenous administration of levodopa (1 mg/kg) was measured by the xenon-enhanced computed tomographic method in six patients with progressive supranuclear palsy (PSP) and in nine patients with idiopathic Parkinson's disease. The baseline LCBF values in most brain regions in patients with PSP were lower than those in patients with Parkinson's disease, and hyperfrontality of the LCBF was lost. In patients with Parkinson's disease, the injection of levodopa markedly increased LCBF, especially in the striatum, thalamus, and internal capsule (approximately 40%). In patients with PSP, however, levodopa did not increase the LCBF in all brain regions examined. The LCBF increases after the administration of levodopa in patients with Parkinson's disease may be secondary to metabolic activation of the dopaminergic system. The different LCBF responses to levodopa between patients with PSP and those with Parkinson's disease may reflect differences in pathologic features, such as in the degree of preservation of nigrostriatal dopaminergic neurons and the distribution and density of dopamine receptors, and are also related to the clinical effectiveness of levodopa therapy.

Aged↗
PubMed1992

Cellular immune responses to retinal antigens in retinitis pigmentosa.

Patients with retinitis pigmentosa and a group of controls were tested for their cellular immune response toward two retinal proteins, S-antigen and interphotoreceptor retinoid-binding protein (IRBP), as well as their reaction against two synthetic peptides ("M" and "N") derived from the sequence of S-antigen and peptide "R14", derived from IRBP. Positive responses to the retinal antigens were found in larger proportions and with higher levels in the patient group than in the controls. The difference between the two groups was statistically significant in their response to S-antigen, but the patients reacted better than the controls against the other antigens as well. Of particular interest was the finding that several patients responded to both retinal proteins and/or to their peptides. These patients suffered from severe retinal changes and the data are thus interpreted as suggesting that the responses to the retinal antigens are secondary to these changes and to nonphysiological release of retinal antigens.

Adult↗
PubMed1992

Regional brain distribution of toluene in rats and in a human autopsy.

Toluene concentrations in 9 brain regions of acutely exposed rats and that in 11 brain regions of a human case who inhaled toluene prior to death are described. After exposure to toluene by inhalation (2000 or 10,000 ppm) for 0.5 h or by oral dosing (400 mg/kg), rats were killed by decapitation 0.5 and 4 h after onset of inhalation and 2 and 10 h after oral ingestion. After each experimental condition the highest range of brain region/blood toluene concentration ratio (BBCR) was in the brain stem regions (2.85-3.22) such as the pons and medulla oblongata, the middle range (1.77-2.12) in the midbrain, thalamus, caudate-putamen, hypothalamus and cerebellum, and the lowest range (1.22-1.64) in the hippocampus and cerebral cortex. These distribution patterns were quite constant. Toluene concentration in various brain regions were unevenly distributed and directly related blood levels. In a human case who had inhaled toluene vapor, the distribution among brain regions was relatively similar to that in rats, the highest concentration ratios being in the corpus callosum (BBCR: 2.66) and the lowest in the hippocampus (BBCR: 1.47).

Adult↗
PubMed1992

Suppression of experimental autoimmune uveitis in rats by the oral administration of the uveitopathogenic S-antigen fragment or a cross-reactive homologous peptide.

The oral administration of S-antigen fragment (a synthetic peptide designated as peptide M and known to be uveitopathogenic for rat, guinea pig, and monkey) to Lewis rats prior to challenge with an emulsion of peptide M and CFA resulted in either a total or partial suppression of experimental autoimmune uveitis (EAU), a T cell-mediated autoimmune disease studied as a model for human uveitis and experimental autoimmune pinealitis (EPA). Both the clinical and histopathologic manifestations of the disease were suppressed in a dose-dependent manner. Pinealitis associated with EAU was also suppressed by the oral administration of peptide M. Additionally, ingestion of a fragment of baker's yeast (Saccharomyces cerevisiae) histone H3, which has five consecutive amino acids identical to peptide M and which has been found to be uveitopathogenic in Lewis rats, induced tolerance to either peptide M or synthetic histone H3 peptide. In addition, the proliferative response to peptide M was inhibited in peptide M-fed rats. The suppression of EAU and in vitro lymphocyte proliferative responses to peptide M were observed to be antigen specific, since oral feeding of a control protein (BSA) exerted no suppressive effect. Furthermore, the T cells isolated from the spleen and lymph nodes of animals rendered tolerant by oral administration of peptide M can transfer protection against EAU adoptively. These results demonstrate that the oral administration of an autoantigen or its homologous peptide initiates an antigen-specific cellular mechanism which may ameliorate EAU.

Administration, Oral↗
PubMed1992

Cerebral microcirculatory changes during and following transient ventricular tachycardia in cats.

Although reduced cerebral perfusion is believed to be the cause of syncope due to cardiac arrhythmias, investigations on the cerebral microcirculation during cardiac arrhythmias have been rare. We therefore studied the effects of transient ventricular tachycardia on the local cerebral blood volume and blood flow. Experimental ventricular tachycardia was induced in cats by electrically stimulating the ventricle of the heart at a rate of 300/min for 1 min. Using our photoelectric method, the local cerebral blood volume, mean transit time of blood, and cerebral blood flow in the parieto-temporal region were measured during and for 3 h after ventricular tachycardia. Transient ventricular tachycardia of as short as 1 min caused cerebral ischemia with a blood flow reduction of approximately 30%. This was considered to be due to reduced blood pressure plus transient autonomic dysfunction, or dysautoregulation, during the ventricular tachycardia. Mild and transient reactive hyperemia occurred immediately after termination of the dysrhythmia, but continuous reductions of cerebral blood flow were observed thereafter for 3 h. This delayed hypoperfusion is attributable to either vasoconstriction of the large resistance vessels or changes in the hemorheological properties of the blood caused by cerebral ischemia. Ventricular tachycardia of the type reported has significant and long-lasting effects on the cerebral microcirculation.

Animals↗
PubMed1992

Estimation of plasma glucose fluctuation with a combination test of hemoglobin A1c and 1,5-anhydroglucitol.

We investigated the effect of plasma glucose fluctuation on hemoglobin A1c (HbA1c) and plasma 1,5-anhydroglucitol (AG) levels, especially in insulin-dependent diabetes mellitus (IDDM). Plasma AG is a new marker that provides sensitive and analytical information on glycemic control. The basic mechanisms underlying both the reduction and recovery of the plasma AG level, ie, the excretion into urine with glucosuria and the amount supplied to the body, were presumed to be similar in IDDM and non-insulin-dependent diabetes mellitus (NIDDM) patients. The correlation coefficient for mean plasma glucose and AG was -.591, and it was .578 for mean plasma glucose and HbA1c in IDDM patients. In NIDDM, the correlation between mean plasma glucose and AG was -.869, and between mean plasma glucose and HbA1c, .875. The plasma AG levels in the IDDM group showed a lower range than in the NIDDM group, even with similar HbA1c levels. All the cases showing lower plasma AG levels among those with similar HbA1c levels manifested greater fluctuation of plasma glucose and a larger amount of urinary glucose. The lower AG level in IDDM patients was reversible to the level in NIDDM patients when the greater fluctuation of plasma glucose was corrected. Thus, it was suggested that because urinary glucose excretion is intermittently high in IDDM patients, plasma AG is frequently low, even though the mean plasma glucose and HbA1c levels suggest good control.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Enhancement of S-antigen and its mRNA in the irides of uveitic patients.

S-antigen (S-Ag) and its mRNA were analysed by immunohistochemistry and in situ hybridization in 32 iridectomy specimens from 29 uveitic patients and 10 non-uveitic patients. S-Ag was detected in one iris and its mRNA was detected in 12 uveitic patients. Neither S-Ag nor its mRNA was found in the controls (P < 0.003). Ten of the 12 patients who had detectable S-Ag mRNA, while only four of the 17 patients who did not, had received corticosteroids for more than 3 years (P = 0.006). We also demonstrated S-Ag and its mRNA in bovine iris by immunoprecipitation and polymerase chain reaction. These results indicate that S-Ag and its mRNA accumulate in the irides of some uveitic patients. This accumulation may be the result of local immunoregulatory factors and an effect of corticosteroid treatment, and may modulate ocular inflammation.

Adrenal Cortex Hormones↗
PubMed1992

Origin and disposal of 1,5-anhydroglucitol, a major polyol in the human body.

The origin and disposal of 1,5-anhydro-D-glucitol (AG), one of the main polyols found in the human body, was studied in normal subjects and diabetic patients. AG was detected in various kinds of foods. The mean AG supplement through foods was estimated to be approximately 4.38 mg/day, which was compatible with that calculated in a food analysis (average 0.22 mg AG/100 kcal in Japanese foods) on eight healthy subjects. The mean AG excretion in urine was approximately 4.76 mg/day in these subjects. Excretion into stools was negligible. From observations on the patients without oral supplement of AG, 0.4 mg of daily de novo synthesis of AG was strongly suggested. It was also implied that urinary AG excretion occurred soon after food ingestion and that its amount was closely correlated with daily supplement through foods. Thus the fundamental kinetics of AG were recognized as follows: 1) AG in the body originates mainly from foods and is well absorbed in the intestine, 2) AG is little degraded and metabolized in the body, and 3) an equilibrium exists between oral supplement plus a small but steady amount of de novo synthesis and excretion in urine.

Adult↗
PubMed1992

Animal species differences in erythrocyte aggregability.

Species differences in erythrocyte aggregability were investigated employing our whole blood erythrocyte aggregometer. Blood was sampled from seven species, including humans and anesthetized (30 mg/kg pentobarbital) animals. The erythrocyte aggregation rates were the following (in s-1): cats, 0.213 +/- 0.027 (means +/- SD); dogs, 0.164 +/- 0.027; men, 0.112 +/- 0.025; rats, 0.111 +/- 0.005; domestic rabbits, 0.049 +/- 0.021; and mongolian gerbils, 0.034 +/- 0.015. Domestic fowls did not exhibit erythrocyte aggregograms like those seen in the other species. Statistical analysis revealed significant differences among the erythrocyte aggregation rates of the different species (multiple-comparisons with an overall significance level of 0.05) except between men and rats and between rabbits and gerbils. No single factor which is known to accelerate the erythrocyte aggregation rate (hematocrit, fibrinogen, etc.) was correlated with the erythrocyte aggregation rate except the globulin concentration in the blood. The failure to detect erythrocyte aggregation in domestic fowls was probably attributable to their erythrocyte shape. These results suggest that each species has its own proper tendency for erythrocyte aggregation. This factor must be taken into consideration when the blood circulation is discussed among different animal species.

Animals↗
PubMed1992

Expression of the angiotensinogen gene and localization of its protein in the human heart.

BACKGROUND: There have been no reports on the presence of the tissue renin-angiotensin system in the human heart, although the presence of angiotensinogen has been described in the animal heart. METHODS AND RESULTS: To determine whether angiotensinogen is synthesized in the human heart, we examined angiotensinogen messenger RNA (mRNA) synthesis in autopsy hearts by using ribonuclease protection assay. As a result, angiotensinogen mRNA was detected in the atrial muscle, muscles of the conduction system, and the left ventricular wall. In the left ventricular wall, mRNA expression was more prominent in the subendocardial muscles than in the midcardial or epicardial muscles. Using a monoclonal antibody to human angiotensinogen in immunoblotting experiments, we detected two closely spaced bands at approximately 70 kd in the heart, which was quite consistent with the human angiotensinogen molecule. Immunohistochemical studies with this monoclonal antibody demonstrated intense immunoreactivity in the atrial muscles, the muscles of the conduction system, and those of the subendocardial layers. CONCLUSIONS: We conclude that angiotensinogen was synthesized in the human heart. It was evident that the localization of angiotensinogen was not ubiquitous in the cardiac muscles, showing its predilection for the atrial muscles, muscles of the conduction system, and subendocardial layer of the left ventricle.

Angiotensin II↗
PubMed1992

Developmental expression of S-antigen in fetal human and rat eye.

Development expression of S-antigen and its mRNA in human and rat fetal retina was studied by immunocytochemical and in situ hybridization techniques. Immunocytochemistry indicated that S-antigen was present after 4 months gestation in the fetal human retina. In the rat, S-antigen was detected in the retina only after birth. In situ hybridization studies indicated that the S-antigen mRNA was present at 13 weeks gestational age in the human and at 15 days in the rat embryo. S-antigen mRNA was expressed not only in the retina but also in ocular tissues of neural crest origin in the fetus.

Adult↗