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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 397 records · Page 22Linked to original sources
PubMed1997

Augmentation of immune response by an analog of the antigenic peptide in a human T-cell clone recognizing mutated Ras-derived peptides.

T-cells that recognize mutated p21 Ras are relevant to immune surveillance systems against cancer. We report here evidence that immune responses of a T-cell clone recognizing mutated p21 Ras can be augmented by an analog peptide. Using spleen cells from a gastric cancer patient, we established the CD4+ alpha beta Th1-like clone C27 that recognizes wild-type (3EYKLVVVGAGGVGKS17) and mutated p21 Ras protein molecules and peptides, in an HLA-DR1-restricted manner. C27 responded prominently to mutated Ras peptides carrying Val or Ala at position 12, as compared to wild-type and other mutated peptides. C27 also exhibited a much stronger response to a mutated p21 Ras whole-protein molecule-carrying Val at position 12, as compared with the wild-type protein. The proliferative response and production of GM-CSF, TNF-alpha, and IFN-gamma by C27 were further augmented by replacing the possible first DR anchor 4Tyr of the mutated Ras peptide with Trp, a more potent anchor residue for the DR1 molecule. Enhancement of peptide antigenicity by substituting the HLA anchor residue of an antigenic peptide recognized by tumor-reactive T-cells may prove to be a novel strategy for antigen-specific cancer immunotherapy.

Adjuvants, Immunologic↗
PubMed1997

Partial activation of human T cells by peptide analogs on live APC: induction of clonal anergy associated with protein tyrosine dephosphorylation.

T-cell clonal anergy induced by peptide analogs in the presence of live APC in murine systems was reported to be associated with incomplete tyrosine phosphorylation of the CD3 zeta chain followed by a lack of subsequent ZAP-70 recruitment. Furthermore, protein tyrosine phosphatase SHP-1 was associated with ZAP-70 upon T-cell activation, leading to a dominant negative signaling. In this study, we used nonself BCGa-specific human ThO clones and investigated the antagonistic/partial agonistic activities of one-residue-substituted analog peptides. The results showed that (a) certain one-residue-substituted analogs can partially activate T cells to produce lymphokines, without proliferation; (b) a peptide with a conservative one-residue substitution can induce T-cell anergy in the presence of live APC, but T cells are capable of responding to exogenously added IL-2; and (c) the induction of anergy is accompanied by marked dephosphorylation of a 110-kDa protein, without either upregulation of CD25 or any changes in CD3 zeta phosphorylation patterns, suggesting that TCR-mediated dominant negative signaling through phosphatase(s) in another mechanism that may lead to the induction of T-cell clonal anergy by altered TCR ligands.

Amino Acid Sequence↗
PubMed1997

The relationship between moyamoya disease and bacterial infection.

To examine the relationship between Moyamoya disease and bacterial infections, authors studied the serum of 85 cases of Moyamoya disease and the influence of Propionibacterium acnes (P. acnes) infection on intracranial arteries in rats. The serum levels of P. acnes antibody, IgM, transferrin (Tf), alpha 2-macroglobulin (alpha 2M) were significantly higher in Moyamoya disease than in normal volunteers. Moyamoya-like changes of the intracranial internal carotid arteries were histopathologically demonstrated in P. acnes infectious rats. These findings suggest that P. acnes and immunological factors might play a role in the pathogenesis of Moyamoya disease.

Adolescent↗
PubMed1997

Reduction of hypoxic cells in solid tumours induced by mild hyperthermia: special reference to differences in changes in the hypoxic fraction between total and quiescent cell populations.

C3H/He mice bearing SCC VII tumours received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps in order to label all proliferating (P) cells. The tumours were then heated at 40 degrees C for 60 min. At various time points after heating, tumour-bearing mice were irradiated while alive or after being killed. Immediately after irradiation, the tumours were excised, minced and trypsinized. The tumour cell suspensions obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labelling, which could be regarded as quiescent (Q) cells, was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P+Q) tumour cell population was determined from the irradiated tumours that were not pretreated with BrdU. The MN frequency of BrdU unlabelled cells was then used to calculate the surviving fraction of the unlabelled cells from the regression line for the relationship between the MN frequency and the surviving fraction of total (P+Q) tumour cells. In general, Q cells contained a greater hypoxic fraction (HF) than the total tumour cell population. Mild heating decreased the HF of Q cells more markedly than in the total cell population, and the minimum values of HFs of both total and Q cell populations were obtained 6 h after heating. Two days after heating, the HF of total tumour cells returned to almost that of unheated tumours. In contrast, the HF of Q cells did not return to the HF level of unheated tumours until 1 week after heating. It was thought that irradiation within 12 h after mild heating might be a potentially promising therapeutic modality for controlling radioresistant Q tumour cells.

Animals↗
PubMed1997

A phase I/II study of a hypoxic cell radiosensitizer KU-2285 in combination with intraoperative radiotherapy.

A fluorinated 2-nitroimidazole radiosensitizer KU-2285 was given before intraoperative radiotherapy (IORT) to 30 patients with unresectable, unresected or macroscopic residual tumours. Twenty-three patients had pancreatic cancer and five had osteosarcoma. The IORT dose was 30 Gy for unresectable pancreatic cancer and 60 Gy for osteosarcoma. The dose of KU-2285 administered ranged from 1 to 9 g m-2. Four patients received a dose of 9 g m-2, and ten received 6.8-7 g m-2. All patients tolerated KU-2285 well, and no drug-related toxicity was observed. The average tumour concentration of KU-2285 immediately after IORT was 166 microg g-1 at dose of 6.8-7 g m-2 and 333 microg g-1 at 9 g m-2. The average tumour-plasma ratio was > or = 0.82. Eleven patients with unresectable but localized pancreatic cancer treated with KU-2285 plus IORT and external beam radiotherapy had a median survival time of 11 months and 1-year local control rate of 50%, which compares favourably with those of 8 months (P = 0.26) and 28% (P = 0.10) for 22 matched historical control patients. The five patients with osteosarcoma attained local control. The results of this first study on KU-2285 and IORT appear encouraging, and further studies of this compound seem to be warranted.

Adolescent↗
PubMed1997

Changes in the activity and mRNA levels of phospholipase D during ceramide-induced apoptosis in rat C6 glial cells.

N-Acetylsphingosine (C2-ceramide), a membrane-permeable analogue, induced apoptosis in C6 glial cells. Phase-contrast micrographs showed that the round cells appeared 3 h after exposure to 25 microM C2-ceramide and the number of floating cells increased time-dependently. Staining with Hoechst 33258 dye showed condensed or fragmented nuclei in round cells at 12 h. DNA fragmentation was also observed by agarose gel electrophoresis at 12 h. To understand the mechanism underlying glial cell death induced by C2-ceramide treatment, changes in phospholipase D (PLD) activity in response to guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) and expression of mRNA levels of PLD isozymes were examined. In cell lysate, GTPgammaS-dependent PLD activity was down-regulated after ceramide treatment in a time-dependent manner. In the in vitro PLD assay, membrane-associated PLD activation in response to recombinant ADP-ribosylation factor 1 was greatly suppressed. Furthermore, levels of rPLD1a and rPLD1b mRNAs were found to be down-regulated, whereas the level of rPLD2 mRNA increased gradually, peaking at 3 h, followed by a slow decrease, as inferred by reverse transcription-polymerase chain reaction. Decreases in GTPgammaS-dependent PLD activity were well correlated with those in rPLD1a and rPLD1b mRNAs levels. Taken together, these data suggest that levels of PLD enzymes might be decreased by ceramide treatment.

ADP-Ribosylation Factors↗
PubMed1997

The difference of means of two indirect unpaired groups in receptor autoradiography.

We present an approximate method to compare the difference of the means of two groups of populations by indirect unpaired data. This indirect data structure occurs in receptor autoradiography, where the tissue distribution of receptors is visualized in the form of ligand bindings. This visualization is indirect because we can only observe and measure nonspecific bindings in one autoradiograph and total bindings in another autoradiograph. The distribution of receptors is obtained by subtracting the nonspecific bindings from the total bindings. Besides the reasoning of our method, an example is given using our experimental data.

Animals↗
PubMed1997

In vivo analysis of Fas antigen-mediated apoptosis: effects of agonistic anti-mouse Fas mAb on thymus, spleen and liver.

Fas antigen (Fas/CD95) is a cell surface receptor protein that mediates apoptosis-inducing signals. To analyze the function of Fas in vivo, we examined the effects of agonistic anti-Fas antibodies in mice. The i.p. administration of the hamster anti-mouse Fas mAb, RK-8, which induced apoptosis both in vivo and in vitro, did not kill adult mice, whereas those given the another hamster anti-mouse Fas mAb, Jo2, rapidly died of fulminant hepatitis with hemorrhage. Histological analyses of mice given RK-8 indicated severe damage of the thymus, and moderate damage of the spleen and liver. Most of the thymocytes and some hepatocytes underwent apoptosis within 1 day of administration. Flow cytometry revealed that CD4+ T cells were more sensitive to Fas-mediated apoptosis than CD8+ T cells. At day 7 after administration, the thymus was atrophied. These in vivo effects of RK-8 were transient; the thymus was regenerated, and the liver and spleen were apparently normal 1 month after injection. The administration of RK-8 into newborn mice caused severe damage of the liver and thymus. Most of the hepatocytes died and jaundice was induced. The newborn mice died within 1 week. Most hepatocytes of newborn mice may be more sensitive to apoptosis-inducing signals through Fas than those of adult mice. These results indicated that functional Fas, which introduces the death signal in vivo, is expressed on thymocytes, CD4+ splenocytes, and some adult and most newborn mouse hepatocytes.

Animals↗
PubMed1997

Comparison of accelerated hyperfractionated radiotherapy and conventional radiotherapy for supratentorial malignant glioma.

Between 1988 and 1993, 71 patients with glioblastoma or anaplastic astrocytoma were treated either with accelerated hyperfractionation radiotherapy (1.5 Gy twice daily to a total dose of 69 Gy, n = 35) or with conventional fractionation radiotherapy (1.8 Gy daily to 64.8 Gy, n = 36). Two patients in each group did not complete radiotherapy, leaving 67 evaluable. All patients received the chemotherapeutic regime ACNU intraarterially (50 mg/m2) or intravenously (100 mg/m2) prior to and after radiotherapy. Between 1990 and 1992, 19 patients also received intravenous interferon-beta (3 x 10(6) U, three times weekly) during radiotherapy. The median survival time was 14.5 months for the accelerated hyperfractionation group and 14 months for the conventional fractionation group. The median time to progression was 12 months for the accelerated hyperfractionation group and 9.5 months for the conventional fractionation group. There was no significant difference in either survival (P = 0.89) or progression-free survival (P = 0.25) between the accelerated hyperfractionation and conventional fractionation groups. Interferon therapy was associated with poorer survival. Brain necrosis developed in four out of 10 patients receiving accelerated hyperfractionation radiotherapy plus interferon-beta, but in none of nine patients receiving conventional fractionation radiotherapy plus interferon (P = 0.033). In conclusion, our study failed to demonstrate any possible benefit of accelerated hyperfractionation radiotherapy for malignant glioma. The incidence of brain necrosis may be increased by combining accelerated hyperfractionation radiotherapy and interferon-beta.

Adult↗
PubMed1997

Identification of indispensable residues for specific DNA-binding in the imperfect tandem repeats of c-Myb R2R3.

The individual repeats, R2 and R3, of the minimum specific DNA-binding domain (R2R3) of c-Myb have very similar structures, with a helix-turn-helix variation motif, although their sequence identity in the tandem repeats is only 31%. From previous mutational and structural studies, the third helices in both repeats were shown to directly recognize the specific base sequence, PyAACG/TG. In order to elucidate the reason for the imperfection of the tandem repeats at amino acid positions other than the recognition helices, a series of R2R3 mutants was generated by swapping the helices and the N-terminus in R2 to those in R3. Consequently, the sequence composing the first helix of R2 was found to be essential for specific DNA-binding, in addition to the third recognition helix of R2. Further mutational studies revealed that the only indispensable residues in the first helix are Val103 and Val1O7, which are involved in the hydrophobic core of R2. These residues do not directly interact with the DNA, but they contribute to the correct formation of helix 1 and the characteristic packing of R2, which is slightly different from that of R3, and are required for specific base recognition through strong cooperativity with R3.

Binding Sites↗
PubMed1997

The relationship between HLA-DRB1 alleles and disease subsets of rheumatoid arthritis in Japanese.

To assess the association between HLA-DRB1 and the pathogenesis of rheumatoid arthritis (RA) in the Japanese population, we typed for HLA-DRB1 alleles in 852 Japanese patients. An analysis of HLA-DRB1 allele associations was performed on the overall group and in three disease subsets of adult-onset RA, classified according to the extent of joint destruction evident on plain radiograms, i.e. least erosive subset (LES), more erosive subset (MES) and most erosive subset with mutilating disease (MUD). The Japanese RA patients with positively associated with DRB1*0101 and *0405, and negatively associated with DRB1*0701, *0802, *1302 and *1405. DRB1*0101 was associated more strongly with a milder disease subset and the relative risk (RR) was 1.9, 1.5 and 1.2 for LES, MES and MUD, respectively. On the other hand, DRB1*0405 was associated more strongly with a more severe disease subset, the RR being 1.8, 4.0 and 4.3 for LES, MES and MUD, respectively. These findings suggest that RA is a heterogeneous disease, not only clinically, but also in terms of its immunogenetic background, and that HLA-DRB1 can be a useful prognostic factor for RA.

Adolescent↗
PubMed1997

Relaxant effects of vasodilator peptides on isolated basilar arteries from stroke-prone spontaneously hypertensive rats.

1. The relaxant of vasodilator peptides were examined in ring preparations of basilar arteries from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats. 2. Vasoactive intestinal peptide and peptide histidine isoleucine produced similar endothelium-independent relaxations in basilar arteries from WKY rats and SHRSP. Calcitonin gene-related peptide (CGRP) elicited endothelium-independent relaxations in both groups and the CGRP-induced relaxation was greater in SHRSP than in WKY rats. Substance P and neurokinin A did nor relax basilar arteries from either group. 3. Both WKY rat and SHRSP basilar arteries were relatively insensitive to atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide. 4. Bradykinin (BK) potently relaxed basilar arteries with endothelium, but BK produced contractions in endothelium-rubbed arteries in both WKY rats and in SHRSP. There was no significant difference in the relaxant response to BK between WKY rat and SHRSP arteries. 5. Adrenomedullin (AM) produced endothelium-independent relaxations in both groups and the relaxant response to AM was significantly greater in SHRSP than in WKY rats. 6. Human CGRP(8-37;mumol/L), a CGRP receptor antagonist, significantly inhibited both relaxant responses induced by CGRP and AM in WKY rats and in SHRSP arteries. 7. Among various peptides tested, the responses to CGRP and AM were higher in basilar arteries from SHRSP than in those from WKY rats. The relaxation produced by AM may be via CGRP receptors in WKY rat and SHRSP basilar arteries.

Adrenomedullin↗
PubMed1997

Preschool sarcoidosis mimicking juvenile rheumatoid arthritis: the significance of gallium scintigraphy and skin biopsy in the differential diagnosis.

Preschool sarcoidosis occurring in children less than 6 years old is rare and characterized by the triad of skin, joint and eye manifestations without any pulmonary lesion. Because of similar clinical manifestations, the diagnosis of preschool sarcoidosis and juvenile rheumatoid arthritis (JRA) is confusing. A girl with preschool sarcoidosis, initially diagnosed and treated as having JRA, is reported here. Ophthalmologic examinations revealed posterior involvement of the eye. A gallium scintigram of the head showed panda appearance. Biopsy of the cutaneous lesion demonstrated non-caseating granuloma. Gallium scanning may be an important clue to correct diagnosis.

Arthritis, Juvenile↗
PubMed1997

A fluid-phase endocytotic capacity and intracellular degradation of a foreign protein (horseradish peroxidase) by lysosomal cysteine proteinases in the rat junctional epithelium.

We investigated the co-localization of lysosomal cathepsins B, H and L, and horseradish peroxidase (HRP) in junctional epithelial (JE) cells both as a fluid-phase endocytotic marker to demonstrate the fluid-phase endocytotic capacity of JE cells, and to understand the morphological relationships of the endocytosed foreign substances to lysosomal cathepsins in these cells. The diaminobenzidine (DAB) histochemical and cytochemical methods and immunohistochemical avidin-biotin-peroxidase complex and immunocytochemical post-embedding colloidal gold methods were used. Under light microscopy, DAB reaction products based on HRP were found in JE but were rare or absent in the oral sulcular epithelium and oral epithelium. Immunolabeling for cathepsins B and H was found in the granular structures of the cells, but no cathepsin L was identified. With electron microscopy, DAB reaction products, which indicated both HRP and the azurophil granules of neutrophils, were endocytosed into JE cells. Using a post-embedding technique, gold particles indicating HRP were present on the plasma membrane of JE cells, at the periphery of electronlucent vacuoles, and in the electrondense granules. Gold particles indicating cathepsin B or H were found in the electrondense granules. With different sizes of colloidal golds, the co-localization of cathepsin B or H with HRP was indicated only in the electrondense portion of the larger vacuoles consisting of electronlucent and -dense parts. This study provided the first morphological data which indicate that JE has a fluid phase endocytotic capacity, and which suggest that the lysosomal cathepsins B and H are involved in the intracellular degradation of foreign substances invading through the gingival sulcus in JE cells.

3,3'-Diaminobenzidine↗
PubMed1997

[An autopsy case of chronic granulomatous disease diagnosed by biopsy].

This report concerns a male patient aged 25 years, diagnosed at the age of 12 years as suffering from chronic granulomatous disease. This patient had p47-phox deficiency. He was admitted to this hospital because of fever and dyspnea accompanied by right spontaneous pneumothorax. He failed to respond to medical treatment. He died from respiratory failure four months after admission. Autopsy demonstrated pigmented lipid histiocytes characteristic of CGD. These characteristic pigmented cells were distributed in the spleen, liver, lymph nodes and in the small intestine. As for the nature of the pigment, lipofuschin-like compound were identified. Granulomatous component was seen in the mucosa of the stomach obtained by operation. The presence and characteristic distribution of such pigmented macrophages in tissue in young adults may suggest the diagnosis of CGD.

Adult↗