Biomedical subjects

T Shinohara

Publications and source records attributed to T Shinohara.

At least 199 records · Page 11Linked to original sources

PubMed1993

Cellular immune response of patients with uveitis to peptide M, a retinal S-antigen fragment.

Peptide M, an 18-amino acid fragment from position 303 to position 320 of retinal S-antigen, produces experimental autoimmune uveitis (EAU), similar to that produced by native S-antigen, in several vertebrate species including nonhuman primates. It was observed that 12 of the 39 (30.7%) patients with uveitis, 1 of the 29 (3.4%) patients with systemic connective tissue disorders (CTD) without eye involvement, 2 of the 7 (5.8%) patients of CTD with uveitis, 1 of the 17 (5.8%) patients with diabetic retinopathy, and none of the 19 normal healthy controls showed a significant lymphoproliferative response to peptide M (stimulation index of 3 or more). Yeast histone H3 peptide gave a positive response in 1 (2.5%), 2 (6.8%), 1 (14.2%), 2 (11.7%), and 2 (10.5%) individuals, respectively, in the different groups studied. In a few cases a positive response to yeast histone H3 peptide was observed without significant stimulation to peptide M. These findings indicate that peptide M could also be an immunogenic epitope of S-antigen in humans and be aetiopathologically related to uveitis in a subset of patients with this disease. However, unlike experimental animals, the responses to peptide M and yeast histone H3 were nonconcordant, necessitating further studies.

Adolescent↗

PubMed1993

The proximal promoter of the mouse arrestin gene directs gene expression in photoreceptor cells and contains an evolutionarily conserved retinal factor-binding site.

Regulatory sequences and nuclear factors governing tissue-restricted expression of the mouse arrestin gene were investigated. The results showed that while proximal promoter sequence positions -38 to +304 are sufficient to direct low levels of retina-specific gene expression, sequences extending upstream to position -209 support higher levels of expression in the retina, as well as detectable expression in the lens, pineal gland, and brain. Within the interval between positions -209 and -38, a broadly expressed nuclear factor, Bd, binds to sequences centered between positions -205 and -185, a region which contains two direct repeats of the hexamer, TGACCT. The proximal promoter binds three apparently retina-specific nuclear factors, Bp1, Bp2, and Bp3, through overlapping sequences centered between positions -25 and -15. Bp1 and Bp3 also recognize a closely related sequence found in the promoter regions of several other vertebrate photoreceptor-specific genes. Moreover, the consensus binding site for Bp1, designated PCE I, is identical to RCS I, an element known to play a critical role eliciting photoreceptor-specific gene expression in Drosophila melanogaster. The results suggest that PCE I and RCS I are functionally as well as structurally similar and that, despite marked differences in the fly and vertebrate visual systems, the transcriptional machinery involved in photoreceptor-specific gene expression has been strongly evolutionarily conserved.

Animals↗

PubMed1993

Megakaryocyte, erythroid and granulocyte-macrophage colony formation in myelodysplastic syndromes.

Bone marrow progenitor cell assays of three cell lineages, i.e., colony-forming unit megakaryocytes (CFU-Meg), burst-forming unit erythrocytes (BFU-E) and colony-forming unit granulocyte-macrophages (CFU-GM), were performed for 21 patients with myelodysplastic syndromes (MDS). Markedly reduced or absent colony formation was found in 67% of the patients for CFU-Meg and all patients except 2 with refractory anemia (RA) for BFU-E. Abnormal CFU-GM colony formation was found in only 5 of 12 patients with RA and RA with ring sideroblasts, in contrast to all of the RA patients with excess of blasts and excess of blasts in transformation. Defective colony formation of all three cell lineages was seen in 63% of the MDS patients. The colony number of CFU-Meg correlated significantly with the numbers of both BFU-E and CFU-GM. These findings indicate that hematopoiesis in MDS patients is disturbed due to a qualitative or quantitative defect at the multipotent stem cell level.

Adolescent↗

PubMed1993

[Combination chemotherapy with carboplatin and etoposide against lung adenocarcinoma in a patient undergoing hemodialysis: a case report].

A 60-year-old male with chronic renal failure undergoing hemodialysis was treated with combination chemotherapy with carboplatin and etoposide against stage IV adenocarcinoma of the lung. Three hundred mg/m2 of carboplatin on day 1, and 50 mg/m2 of etoposide on days 1 and 3 were injected intravenously before hemodialysis. Pharmacokinetic results revealed that carboplatin was dialyzed. No severe side effects were observed. These observations suggest that combination chemotherapy with carboplatin and etoposide seemed to be applicable to the patients with chronic renal failure undergoing hemodialysis.

Adenocarcinoma↗

PubMed1993

[Experimental studies of postmortem diffusion of toluene in blood, brain, muscle and fat of rats exposed to toluene vapor].

This report describes the postmortem diffusion of toluene in blood, brain, muscle and fat of rats exposed to toluene vapor. After exposure to toluene vapor (4,000 ppm) for 15 and 60 min, rats were killed by CO2 exposure and left for 12 and 24 hours in a fresh air. Toluene concentrations in blood, brain, muscle and fat were determined by head space gas chromatography. Postmortem decrease of toluene concentration in blood and increase of that in fat were observed with postmortem interval in both exposure conditions. But an extremely larger postmortem changes in the short exposure than those in the long exposure were observed. These are due to the facts that the value of fat/blood toluene concentration ratio at the time of death in the short exposure (3.3) was extremely smaller than that in the long exposure (10.5). Postmortem increase in muscle was also observed slightly. Postmortem concentrations in brain in both exposure intervals were relatively constant during these experiments. This postmortem stability is attributable to its anatomical features. These results suggest that brain toluene concentration at the autopsy is useful for the estimation of blood toluene concentration at the time of death and by comparison between toluene concentration in blood and that in brain it may be possible to presume the circumstances of death.

Adipose Tissue↗

PubMed1993

[In vitro studies of the metabolism of paraquat and diquat using rat liver homogenates--isolation and identification of the metabolites of paraquat and diquat].

The metabolism of paraquat and diquat was studied in vitro using rat liver homogenates, and the resulting metabolites were identified. Rat liver was homogenized with three volumes of isotonic buffer, and aliquots of the homogenate were preheated in a boiling water bath for 5 min prior to use. One milliliter of a mixture including both paraquat and diquat in an isotonic buffer solution (10 micrograms ion/ml) was incubated with an equal volume of fresh or preheated homogenate for 1 to 60 min at 37 degrees C. Quantification of paraquat and diquat was carried out by high-performance liquid chromatography (HPLC). In the fresh homogenate, a gradual decrease of paraquat concentration (about a 30% decrease over 60 min of incubation) and a rapid decrease of diquat concentration (not detectable after 10 min of incubation) were observed, but the same phenomenon was not evident with the preheated homogenate. Analysis of the incubated mixture of fresh liver homogenate with paraquat and diquat revealed three unknown peaks on the HPLC chromatograms; these seemed to be breakdown products of paraquant and diquat. The products were isolated and purified from the mixture by Sep-Pak C18 cartridge extraction, HPLC, silica gel column chromatography and Sephadex LH-20 column chromatography. Analysis of the chemical structure of the purified compounds was performed by infrared spectroscopy, mass spectrometry and nuclear magnetic resonance spectroscopy. These analyses determined that paraquat-monopyridone (1',2'-dihydro-1,1'-dimethyl-2-oxo-4,4'-bipyridylium ion) was derived from paraquat, and that diquat-monopyridone (6,7-dihydro-4-oxodipyrido [1,2-a':2',1'-c] pyrazinium ion) and diquat-dipyridone (6,7-dihydrodipyrido [1,2-a:2',1'-c] pyrazine-4,9-dione) were derived from diquat. These results indicate that paraquat and diquat are metabolized by rat liver homogenate, diquat more readily so than paraquat. As the toxicity of these metabolites has been reported to be much lower than those of the parental compounds, it would seem that there is a system capable of detoxifying paraquat and diquat in rat liver.

Animals↗

PubMed1993

Hymenoptera sting anaphylaxis: detection and clinical significance of individual bee and wasp venoms specific IgE and IgG4 antibodies.

In Japan, an average of 37 fatalities per year related to bee or wasp stings were reported during the years 1979-1988. To confirm fatal anaphylaxis serologically, we measured bee or wasp venom specific IgE (sIgE) and IgG4 (sIgG4) antibodies in the sera of 22 patients who visited hospitals with either allergic or anaphylactic reactions after bee or wasp stings by using Enzyme-Linked Immunosorbent Assay. Specific IgE or IgG4 antibodies against Polistes apachus (Paper wasp) and/or a mixture of Polistes annularis, P. exceramans, P. fuscatus, and P. metricus venoms of Polistes genus were detected in 11 patients and the detection frequencies were the highest among positive antibodies against bee or wasp venoms. The severity of allergic reactions was graded from 0-4 according to Mueller. The detection frequencies of sIgE in Mueller grade 0-3 patients were in the range of 33% to 67%, and in grade 4 were 100%. Whereas, the detection frequency of sIgG4 was high (67-100%) in grade 2-4 patients. Especially high levels of sIgE and sIgG4 were detected in patients experiencing the most severe clinical reactions. The detection of venom specific IgE and IgG4 antibodies appears to be useful when determining bee or wasp stings as the cause of fatalities.

Adult↗

PubMed1993

A comparative study of ethanol absorption in the canine jejunum after pretreatment with cyanamide or pyrazole.

This report describes the retardation of ethanol absorption from the intestinal tract and reduction of portal blood flow by high acetaldehyde concentrations in dogs using a jejunal segment with the vascular supply intact. The cyanamide-pretreatment group (CY), in which an extremely high acetaldehyde concentration developed, in comparison with the control and pyrazole-pretreated (PY) groups, showed a gradual increase of portal blood ethanol, a 25% reduction in the amount of absorbed ethanol, and an 85% smaller absorption rate constant value (Ka). These facts indicate that the presence of a high acetaldehyde concentration in the blood results in a reduction of ethanol absorption and retardation of ethanol reaching the systemic circulation. The rapid reduction of portal blood flow and the lower ethanol level in the portal vein observed in the CY group, in comparison with the other two groups, also indicate that the reduction of ethanol permeability through the absorption site to the blood is an important retarding factor induced by acetaldehyde.

Acetaldehyde↗

PubMed1993

Correlation between the physiologic and morphologic changes in experimental autoimmune uveitis induced by peptide G of S-antigen.

PURPOSE: The authors followed and correlated the physiologic and morphologic changes occurring in experimental autoimmune uveitis (EAU) induced by the peptide G of S-antigen. METHODS: EAU was induced in Lewis rats by footpad inoculation of a 13-amino acid synthetic peptide (peptide G) in complete Freund's adjuvant. Electroretinography (ERG) was used to follow the physiologic changes, and light and electron microscopy were used to examine the morphologic changes. RESULTS: Serial ERG recordings showed a progressive decrease in the b-wave amplitude and a depression of retinal sensitivity beginning on day 18-21 postinoculation (PI). By day 35 PI, the b-wave was decreased by 91%, and the sensitivity was depressed by 4.68 log units. Negative ERG were recorded during the intermediate and late stage. Light and electron microscopy of the retina showed better correlation of the pathologic changes with b-wave depression than with PI day. CONCLUSIONS: ERG recordings were a good method to detect, follow, and quantify the severity of EAU. Their good correlation with the morphologic changes showed that this method can be used to assess the condition of the retina noninvasively.

Amino Acid Sequence↗

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↗