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Biomedical subjects

T Shinohara

Publications and source records attributed to T Shinohara.

At least 181 records · Page 10Linked to original sources
PubMed1994

A single amino acid substitution in core residues of S-antigen prevents experimental autoimmune uveitis.

We have previously reported that microbial Ags, having a three- to six-amino-acid-sequence homology with a uveitopathogenic epitope (peptide M) of retinal soluble protein (S-Ag), induce experimental autoimmune uveitis (EAU). Another uveitopathogenic epitope (peptide G) of S-Ag also was characterized. In addition, we have characterized the core sequences by truncating peptides G and M from amino acid and carboxyl termini. In this study, we have further defined the core sequences using synthetic octapeptides with a single amino acid substitution. In addition, the analogues of peptides Gm5 or Mm4 are capable of inhibiting the proliferative response of T-lymphocytes from rats immunized with peptides G-8 or M-8, respectively. Co-injection of a pathogenic peptide with nonpathogenic substitution analogues blocked the induction of EAU. These results suggest that specific nonpathogenic analogues with single amino acid substitution derived from pathogenic peptides have potential for prevention and therapy of autoimmune diseases.

Amino Acid Sequence↗
PubMed1994

The sequence of the human phosducin gene (PDC) and its 5'-flanking region.

Phosducin, a principal protein of the retinal photoreceptor cells, modulates the phototransduction cascade by interacting with transducin. Recently, it has been reported that phosducin is a protein virtually identical to the G-protein inhibitor protein (GIP) in brain. Here, we have sequenced the complete human gene (PDC) and 2215 bp of its 5'-flanking region. The gene is 18 kb in length and has four exons and three introns. The splicing sites for donor and acceptor are in good agreement with the GT/AG rule. Comparative studies of human and mouse phosducin revealed highly homologous sequences. Both the human phosducin gene and a mutant gene locus for Usher syndrome type II have been assigned to chromosome 1q25-q32. The association of this gene with a human disease locus suggests that phosducin may be a potential candidate gene for this disorder.

Animals↗
PubMed1994

Corticosteroids enhance S-antigen expression in nonretinal ocular tissues of rats with experimental autoimmune uveitis.

S-antigen (S-Ag), a major protein on the retinal photoreceptor cell, can induce experimental autoimmune uveitis (EAU). We have previously detected S-Ag and its mRNA in irises of chronic uveitis patients receiving long-term steroid therapy. To further investigate the effect of steroid therapy on ocular tissue, we compared levels of S-Ag and its mRNA in EAU rats with and without steroid treatment. EAU was induced in 72 Lewis rats by two footpad injections of S-Ag. The rats were then treated with Depo-Medrol or phosphate-buffered saline by intramuscular injection. Eyes were collected at different time points. S-Ag mRNA was detected in the lens epithelium, trabecular meshwork, iris, and ciliary body of 47.2% of the steroid-treated group vs 22.2% of the controls. S-antigen was also detected in 30.6% of the eyes of the treated group vs 16.7% of the controls. S-Ag and its mRNA was found only in the retina of normal rats. These results support the hypothesis that prolonged corticosteroid therapy in uveitic patients might enhance the expression of S-Ag in nonretinal ocular tissues and might contribute to the ocular side effects of corticosteroid.

Animals↗
PubMed1994

Structure and chromosomal localization of the human PD-1 gene (PDCD1).

A cDNA encoding mouse PD-1, a member of the immunoglobulin superfamily was previously isolated from apoptosis-induced cells by subtractive hybridization. To determine the structure and chromosomal location of the human PD-1 gene, we screened a human T cell cDNA library by mouse PD-1 probe and isolated a cDNA coding for the human PD-1 protein. The deduced amino acid sequence of human PD-1 was 60% identical to the mouse counterpart, and a putative tyrosine kinase-association motif was well conserved. The human PD-1 gene was mapped to 2q37.3 by chromosomal in situ hybridization.

Amino Acid Sequence↗
PubMed1994

Cone cells fail to develop normally in transgenic mice showing ablation of rod photoreceptor cells.

Transgenic mice were derived containing the cytotoxic dt-alpha gene driven by opsin promoter sequences. Mice expressing this construct showed progressive degeneration of rod photoreceptor cells commencing at birth, with obvious depletion of such cells by postnatal day 7. Ablation of rod photoreceptor cells in the transgenic retina was accompanied by the failure of developing cone cells to elaborate outer segments, although all other aspects of cone cell cytodifferentiation appeared normal. The results suggest that the 1.0-kb opsin promoter segment contains rod cell type specificity and that cone cells require maturation of rod cells to complete the late stages of their terminal differentiation and for their maintenance and cellular integrity.

Animals↗
PubMed1994

Pro-carboxypeptidase R cleaves bradykinin following activation.

Arginine carboxypeptidase (CPR) is a labile enzyme present in human serum which is unrelated to carboxypeptidase N. In this study we demonstrate that CPR exists in a precursor form in plasma and can be converted to the active form by trypsin and presumable trypsin-like enzymes. The trypsin-generated active form can not only cleave a small synthetic substrate, hippuryl-L-arginine, but can remove terminal arginine from bradykinin.

Bradykinin↗
PubMed1994

Midpontine tegmentum infarction with "one-and-a-half syndrome" demonstrated by magnetic resonance imaging.

Magnetic resonance imaging (MRI) revealed a small midpontine tegmentum infarction in a patient with Fisher's one-and-a-half syndrome. The lesion was extremely restricted to the unilateral paramedian area of the midpontine tegmentum involving both the paramedian pontine reticular formation and medial longitudinal fasciculus. The typical form of this syndrome, that is, a combination of lateral gaze palsy and unilateral internuclear ophthalmoplegia, can be caused by a midpontine lesion.

Aged↗
PubMed1993

The sequence of the mouse phosducin-encoding gene and its 5'-flanking region.

Phosducin (Pd), a principal protein of retinal photoreceptor cells, modulates the phototransduction cascade by interacting with transducin. A recent report indicated that Pd and the G-protein-inhibitor protein (GIP) in brain are virtually identical. Here, we have sequenced the complete mouse clone (P1-AT) carrying the Pd gene, 3026 bp of its 5'-flanking region, and cDNAs generated from the retinal mRNAs. Gene Pd is 15 kb in length and has four exons. The splice sites for donor and acceptor were in good agreement with the GT/AG rule. Deduced Pd amino acid sequences were highly homologous to those of human, bovine and rat. In addition, we found more than one similar Pd gene and two different mRNAs. The P1-AT clone encodes one of the Pd mRNAs. These results open the possibility that the multiple Pd genes encode multiple Pd.

Animals↗
PubMed1993

Oligopeptides of three to five residues derived from uveitopathogenic sites of retinal S-antigen induce experimental autoimmune uveitis (EAU) in Lewis rats.

We have previously reported that microbial peptides having 3 to 6 amino acid sequence homology with uveitopathogenic peptide of retinal S-antigen (S-Ag) are capable of inducing experimental autoimmune uveitis (EAU) in Lewis rats and subhuman primates. T-cells obtained from animals immunized with these microbial peptides proliferate when stimulated with S-Ag peptide in culture and vice versa. We were interested to know whether these 3 to 6 identical amino acid residues by themselves were sufficient to induce EAU in susceptible animals under optimal conditions. For this purpose we have determined the response of synthetic oligopeptides of 3 to 18 amino acid residues for their ability to indice EAU. Here, we report that small synthetic oligopeptides of 3 to 5 amino acid residues of the two uveitopathogenic peptides of S-Ag induced EAU in Lewis rats, although with a higher dose (2000 micrograms/rat) than that of the larger peptides (50 micrograms/rat). These results define the core sequences in the uveitopathogenic peptides of retinal S-Ag.

Amino Acid Sequence↗
PubMed1993

Loss of heterozygosity on chromosome arm 17p in small cell lung carcinomas, but not in neurofibromas, in a patient with von Recklinghausen neurofibromatosis.

BACKGROUND: It has been suggested that the genetic abnormality responsible for von Recklinghausen neurofibromatosis (NF1) increases a patient's risk of various kinds of malignancies. The incidence of small cell lung carcinoma (SCLC) as a complication of NF1, however, is rare. To clarify the relationship between NF1 and SCLC, possible loss of heterozygosity of chromosome 17 in a patient with SCLC combined with NF1 was analyzed. METHODS: Possible loss of heterozygosity for chromosome 17 was analyzed by a molecular genetic approach using several chromosome 17-specific polymorphic DNA markers. RESULTS: In both primary tumor and metastatic tumors of SCLC, loss of heterozygosity was detected on chromosome arm 17p, but not on 17q. Loss of heterozygosity, however, was detected on neither 17p nor 17q in neurofibromas and normal tissue. CONCLUSIONS: The formation of SCLC may result from several genetic alterations, including inactivation of tumor-suppressor gene on chromosome 17p, most likely P53, although it still is unknown whether or not a mutation of the NF1 gene on 17q was involved in the development of SCLC in this patient.

Alleles↗
PubMed1993

BK virus infection of the human urinary tract.

By screening consecutive autopsy cases with an antibody that recognizes human polyomaviruses, we found a case of malignant lymphoma in which the virus infection was confined to epithelia of the renal calyces, renal pelvis, ureter, and urinary bladder. The virus was confirmed as BK virus by a specific monoclonal antibody against BK virus T antigen, and numerous virus particles were identified by electron microscopy. The results showed that BK virus is a human urotheliotrophic virus.

Antibodies, Monoclonal↗
PubMed1993

Immunization with recombinant Escherichia coli expressing retinal S-antigen-induced experimental autoimmune uveitis (EAU) in Lewis rats.

Previously we have reported that microbial proteins having sequence homology with uveito-pathogenic peptide (peptide M) of retinal S-antigen (S-Ag) induced experimental autoimmune uveitis (EAU) in Lewis rats and subhuman primates. In order to evaluate the role of natural microbial infections in causing autoimmune diseases we have constructed a recombinant Escherichia coli expressing retinal S-Ag when injected it into Lewis rats which developed EAU. Control animals immunized with E. coli JM105 transfected with only plasmid DNA did not induce EAU. Similarly, baker's yeast (Saccharomyces cerevisiae), which has six amino acid residues in histone H3 identical with peptide M of S-Ag, induced EAU when injected into rats. Lymph node cells of rats immunized with recombinant E. coli or with the yeast show significant proliferative responses against peptide G and peptide M of S-Ag, respectively. The animals immunized with recombinant E. coli also produced antibody to S-Ag.

Animals↗
PubMed1993

Decrease in aortic distensibility after an extended aortic reconstruction for Marfan's syndrome as a cause of postoperative acute aortic dissection DeBakey type I: a report of two cases.

Two cases of Marfan's syndrome underwent a reconstruction of the abdominal aorta and descending thoracic aorta. A replacement of the abdominal aorta with visceral arteries as well as a wrapping of the descending thoracic aorta was performed in case 1 while a reconstruction of the descending thoracic aorta and infra-renal abdominal aorta was done in case 2. After the reconstruction, both cases developed acute aortic dissection DeBakey type I. Another reconstruction of the ascending aorta was then urgently performed. Cardiac catheterization after the second operation in case 1 revealed that the distensibility of the aorta had disappeared at the location of the vascular prosthesis while it had also decreased at the wrapped portion, and the maximum dp/dt of the ascending aorta also increased. Increases in the pulse pressure and pulse rate after the first operation were observed in both cases. These hemodynamic changes, which were produced by a decreased distensibility of the reconstructed aorta, increased the mechanical stress to the native aortic wall, and may have been one of the causes of acute aortic dissection DeBakey type I occurring after reconstruction with a prosthesis.

Acute Disease↗