Search PubMedSearch

Biomedical subjects

Y Tanaka

Publications and source records attributed to Y Tanaka.

At least 19 recordsLinked to original sources

Differential expression of VLA-alpha 4 and VLA-beta 1 discriminates multiple subsets of CD4+CD45R0+ "memory" T cells.

Given the importance of adhesion in T cell development, we have undertaken systematic flow cytometric analysis of CD4 T cells to determine relationships between the developmentally regulated marker CD45R0 and adhesion receptors (five VLA integrin chains). The most important findings are that: 1) expression of alpha 3, alpha 5, and alpha 6 are closely coregulated with beta 1 on CD4 cells, while regulation of VLA-alpha 4 is quite discordant. 2) CD45R0- cells, generally understood to be naive cells, have low homogeneous expression of VLA-alpha 3, VLA-alpha 4, VLA-alpha 5, VLA-alpha 6, and beta 1 integrin chains; studies of cord blood CD4 cells confirm the low homogeneous expression of alpha 4 and beta 1 on naive cells. 3) In marked contrast, CD45R0+ cells, generally understood to be memory cells, show not only an overall increase in expression of these integrins (relative to CD45R0- cells) but also heterogeneity. Dramatic heterogeneity is revealed when the markers VLA-alpha 4 and beta 1 are analyzed together. Many CD45R0+ cells show increased levels of both VLA-alpha 4 and VLA-beta 1; however, some have increased levels principally of either VLA-beta 1 or VLA-alpha 4. We hypothesize that T cells becoming memory cells in different microenvironments specialize their integrin phenotype, thereby acquiring distinctive functional and homing capacities; in this process, VLA-4 (CD49d) appears to play a unique role.

CD4-Positive T-Lymphocytes

Partial purification and characterization of an endo-alpha-N-acetylgalactosaminidase from the culture medium of Streptomyces sp. OH-11242.

For the purification of a new type of endo-alpha-N-acetylgalactosaminidase from the culture medium of Streptomyces sp. OH-11242 (endo-GalNAc-ase-S) [Iwase, Ishii, Ishihara, Tanaka, Omura & Hotta (1988) Biochem. Biophys. Res. Commun. 151, 422-428], a method for assaying enzyme activity was established. Using purified pig gastric mucus glycoprotein (PGM) as the substrate, oligosaccharides liberated from PGM were pyridylaminated, and the reducing terminal sugars of oligosaccharides larger than Gal beta 1-3GalNAc were analysed by h.p.1.c. The crude enzyme of endo-GalNAc-ase-S was prepared as an 80% (w/v) ammonium sulphate precipitate from the concentrated culture medium. The enzyme was partially purified by gel chromatofocusing and subsequent DEAE-Toyopearl chromatography. Endo-enzyme activity eluted around pI 4.8 on a gel chromatofocusing column and eluted with 0.19-0.25 M-NaCl on a DEAE-Toyopearl column. In the enzyme fraction obtained, no exo-glycosidases or proteases could be detected. The molecular mass of the enzyme was estimated as 105 kDa by gel filtration, and the optimum pH was 5.5. Endo-GalNAc-ase-S hydrolysed the O-glycosidic linkage between GalNAc and Ser (Thr) in 3H-labelled and unlabelled asialofetuin, liberating both the disaccharide (Gal beta 1-3GalNAc) and the tetrasaccharide [Gal beta 1-3 (Gal beta 1-4GlcNAc beta 1-6)GalNAc]. When endo-alpha-N-acetylgalactosaminidase from Alcaligenes sp. (endo-GalNac-ase-A) was incubated with 3H-labelled and unlabelled asialofetuin, only the disaccharide (Gal beta 1-3GalNAc) was liberated.

Asialoglycoproteins

Thymic depletion and peripheral activation of class I major histocompatibility complex-restricted T cells by soluble peptide in T-cell receptor transgenic mice.

Injection of mice transgenic for a class I major histocompatibility complex-restricted T-cell receptor with a soluble peptide antigen from influenza virus nucleoprotein results in clonal depletion of double-positive immature thymocytes in the thymus and activation of mature T cells in the periphery, accompanied by a transient up-regulation of the T-cell receptor and CD3 and CD8 coreceptor molecules.

Animals

[Hydralazine-induced enhancement of hyperthermia treatment in vivo].

Hydralazine (Hyd) is a vaso-active drug that significantly affects the nature of blood flow in tumors. As a result, Hyd reduces blood flow and oxygen tension in tumors, causing an increase in the toxic effect of hyperthermia treatment. We investigated enhancement of the anti-tumor effect of hyperthermia by Hyd on SCC-VII tumors in C3H mice. Hyd was administered by intraperitoneal injection, and tumors were heated by water bath. We measured the tumor temperature in animals receiving Hyd by thermocouple. We found no significant change in tumor temperature with Hyd treatment. The effect of Hyd (2.5 mg/kg, 5.0 mg/kg, 7.5 mg/kg) on tumors was evaluated in terms of a growth delay value at which tumor volume reached four-fold. The growth delay values obtained were 6.25 +/- 0.82, 7.14 +/- 0.90, 8.50 +/- 0.98, 9.72 +/- 0.92, and 9.84 +/- 1.3 days for: hyperthermia alone, Hyd of 1.0 mg/kg, 2.5 mg/kg, 5.0 mg/kg, respectively. This effect was independent of the time course of administration of Hyd. These results indicate that Hyd can increase the therapeutic efficacy of hyperthermia treatment. Changes in the microenvironment, such as low pH and tumor hypoxia, induced by arterial embolization may have increased the sensitivity of tumors to heat.

Animals

Chronological expression of microtubule-associated proteins (MAPs) in EC cell P19 after neuronal induction by retinoic acid.

Pluripotent murine embryonal carcinoma (EC) P19 cells are induced at a high rate into neural cells using retinoic acid and serum-free medium. EM observation revealed great increase of microtubules (MTs) after neuronal induction. To study the expression of microtubule-associated proteins (MAPs), immunoblotting and immunocytochemistry were performed with phosphorylated MAP1B (pMAP1B)-, MAP2-, and MAP1A-specific monoclonal antibodies. They did not stain undifferentiated cells. Early MAPs (pMAP1B and MAP2C) appeared 12 h after the neuronal induction, changing to late MAPs (MAP1A and MAP2A/B) at 3-5 days. These expression patterns are quite similar to those of neural cells in vivo. Anti-pMAP1B stained not only neurites but also the cell body and varicosities. But after extraction of the soluble component by permeabilization, pMAP1B was found in only MT-domains of the neurites at LM and EM levels, indicating that some part of pMAP1B is a structural component of neurite MTs and others exist in a soluble form. After culturing for more than 5 days, pMAP1B disappeared from the soma, but still remained in the distal ends of neurites. Here we showed that P19 is a good model system for studying the expression of MAPs on the continuous course of neuronal differentiation.

Animals

[CT of pulmonary dirofilariasis--differential diagnosis from lung cancer].

We present here four cases of pulmonary dirofilariasis in which histological examination of the surgical specimen showed occlusion of the peripheral pulmonary artery by filariae and formation of a necrotic mass surrounded by reactive inflammation and hemorrhage. Radiological examination showed a solitary pulmonary nodule in three cases and a wedge-shaped consolidation in one case. Although pulmonary nodules in dirofilariasis closely mimic bronchogenic carcinoma on radiographs , it is possible to distinguish them from bronchogenic carcinoma on the basis of the following findings: (1) coexistence of subtle satellite lesions, (2) absence of pleural involvement, (3) fine marginal speculations, and (4) lack of concentric marginal speculations (eccentric speculation). In each case of dirofilariasis, CT showed the peripheral pulmonary artery entering the mass. This finding differentiates this disease from metastatic lung tumor, because in tumor metastasis via the pulmonary arteries, visible vessels are not usually involved.

Aged

Carboxyl-terminal tripeptide of alpha-melanocyte-stimulating hormone antagonizes interleukin-1-induced anorexia.

Interleukin-1 beta (IL-1), a cytokine released from inflammatory cells, is thought to be involved in the anorexia associated with severe infection. To assess a possible role of the amino acid sequence found in the supposed IL-1 receptor binding sites, we determined the antagonistic effects of alpha-melanocyte-stimulating hormone (MSH) and the carboxyl-terminal tripeptide of alpha-MSH-(11-13) (alpha-MSH-(11-13)) on the anorexia induced by intracerebroventricular (i.c.v.) administration of 0.5 pmol IL-1. The parent alpha-MSH molecule completely prevented the induction of anorexia by IL-1 at both doses tested, 0.5 and 5.0 pmol. In contrast, alpha-MSH-(11-13) prevented the IL-1-induced anorexia only at 5.0 pmol, but not at 0.5 pmol. Intracerebroventricular injection of 5 pmol of the parent alpha-MSH molecule alone temporarily decreased food consumption at 1-2 h; 5.0 pmol of alpha-MSH-(11-13) alone did not affect food consumption. These data indicate that alpha-MSH can antagonize the anorexic effects of IL-1. The carboxyl-terminal tripeptide portion of alpha-MSH may be important for the antagonistic action of alpha-MSH on the anorexia induced by IL-1.

Amino Acid Sequence

Super helix formation of actin filaments in an in vitro motile system.

Muscle contraction results from relative sliding of actin and myosin filaments. However, the possibility that actin filaments twist or rotate during sliding has not yet been experimentally investigated. We found that a super helix of an actin filament is formed in an in vitro motile system. This fact suggests that an actin filament twists and rotates due to a torque component of a sliding force generated at cross-bridges.

Actin Cytoskeleton

Identification of new epitopes recognized by human monoclonal antibodies with neutralizing and antibody-dependent cellular cytotoxicity activities specific for human T cell leukemia virus type 1.

We have generated a number of EBV-transformed B cell lines producing human mAb against human T cell leukemia virus type 1 (HTLV-1) from the peripheral blood B lymphocytes obtained from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis. Various synthetic peptides corresponding to antigenic regions of HTLV-1 gag and env proteins were used for the screening of antibodies in ELISA. In our study, four IgG mAb to the gag p19 amino acids 100 to 130, and 5 IgG mAb to the env p46 amino acids 175 to 199 were characterized. An immunofluorescence assay showed that all of these mAb specifically bound to the surface of HTLV-1-bearing cell lines. Among these mAb, one anti-gp46 mAb, designated KE36-11, neutralized the infectivity of HTLV-1 as determined by both the inhibition of HTLV-1-induced syncytium formation and transformation assays in vitro. An antibody-binding assay using overlapping oligopeptides revealed that KE36-11 recognized a new epitope locating between the gp46 amino acid sequence 187-193 (Ala-Pro-Pro-Leu-Leu-Pro-His). Another anti-gp46 mAb, designated KE36-7, showed antibody-dependent cellular cytotoxicity against HTLV-1-bearing cell line. KE36-7 bound strongly to the 10-mer peptide-gp46 187-196, and weakly to peptides containing the gp46 amino acid sequence 191-196 (Leu-Pro-His-Ser-Asn-Leu). These two epitopes, which are associated with HTLV-1 neutralization and antibody-dependent cellular cytotoxicity, are thus the first epitopes identified in human HTLV-1 infection. It is possible that passive immunization of humans with these two human mAb are effective on the protection of HTLV-1 infection in vivo.

Amino Acid Sequence

[Conformation radiotherapy of carcinoma of the prostate].

During the period from 1975 to 1989, 84 patients with carcinoma of the prostate were treated with conformation radiotherapy at Tokyo Metropolitan Komagome Hospital. The radiation field encompassed only the area of the prostate gland; it did not include the pelvic lymph nodes. The clinical stage of the 84 tumors was 22 in Stage A, 31 in Stage B, 15 in Stage C and 16 in Stage D. The average age of patients was 73.4 years, with range of 54 to 88 years. The average dose to the tumor was 65.7 Gy, with range of 60 Gy to 70 Gy. Hormone therapy was applied to 42 cases. The 5- and 10-year cumulative survival rates were 90.7% and 70.5% for Stage A, 41.7% and 26.7% for Stage B, 48.9% and 48.9% for Stage C, and 32.6% and 0% for Stage D, respectively. The 5-year cause-specific cumulative survival rates were 100% for Stage A, 92.3% for Stage B, 65.0% for Stage C and 40.3% for Stage D, respectively. Patients with poorly differentiated adenocarcinomas or undifferentiated carcinomas showed poorer survival than those with well-differentiated carcinoma. Only 7 cases suffered in-field recurrence, and 2 cases suffered recurrence at pelvic lymph nodes. Acute reactions were noted in 13 cases. Late complications following treatment were acceptable. Mild to moderate complications were recognized in 2 cases, but neither patient required surgery. In conclusion, our data suggest the advantage of the conformation technique applied to radiation therapy for carcinoma of the prostate.

Aged

Androst-5-ene-7,17-dione: a novel class of suicide substrate of aromatase.

5-En-7-one steroid 1 was found to be a potent inhibitor of aromatase. This along with its 19-hydroxy derivative 7 was characterized as suicide substrate of human placental aromatase (k(inact)'s of 0.069 and 0.058 min-1 and KI's of 143 nM and 11.1 microM, respectively, for steroids 1 and 7). The results suggest that the 19-oxygenation would be involved in the irreversible inactivation of aromatase by the 5-en-7-one steroids.

Androstenedione

CD31 expressed on distinctive T cell subsets is a preferential amplifier of beta 1 integrin-mediated adhesion.

The CD31 (platelet endothelial cell adhesion molecule-1 [PECAM-1]/endothelial cell adhesion molecule [endoCAM]) molecule expressed on leukocytes, platelets, and endothelial cells is postulated to mediate adhesion to endothelial cells and thereby function in immunity, inflammation, and wound healing. We report the following novel features of CD31 which suggests a role for it in adhesion amplification of unique T cell subsets: (a) engagement of CD31 induces the adhesive function of beta 1 and beta 2 integrins; (b) adhesion induction by CD31 immunoglobulin G (IgG) monoclonal antibodies (mAbs) is sensitive, requiring only bivalent mAb; (c) CD31 mAb induces adhesion rapidly, but it is transient; (d) unique subsets of CD4+ and CD8+ T cells express CD31, including all naive (CD45RA+) CD8 T cells; and (e) CD31 induction is selective, inducing adhesive function of beta 1 integrins, particularly very late antigen-4, more efficiently than the beta 2 integrin lymphocyte function-associated antigen-1. Conversely, CD3 is more effective in inducing beta 2-mediated adhesion. Taken together, these findings indicate that unique T cell subsets express CD31, and CD31 has the capacity to induce integrin-mediated adhesion of T cells in a sensitive and selective fashion. We propose that, in collaboration with other receptors/ligands, CD31 functions in an "adhesion cascade" by amplifying integrin-mediated adhesion of CD31+ T cells to other cells, particularly endothelial cells.

Antibodies, Monoclonal

[Radiation management of retinoblastoma].

Forty-five patients with retinoblastoma were treated at Keio University Hospital from 1970 to 1990. Thirty-two patients had unilateral lesions and 13 had bilateral lesions. Twenty-nine patients with unilateral and 12 with bilateral lesions underwent enucleation for advanced tumor. As a result, 3 patients with unilateral retinoblastoma and all patients with bilateral disease were treated with radiotherapy (40-50 Gy) combined with or without cryotherapy and/or photocoagulation. One patient with unilateral lesion treated with radiotherapy and chemotherapy had metastases at the first visit to our clinic and was excluded from this analysis. Among 16 eyes (15 patients) treated with radiotherapy, 6 eyes had recurrence and needed retreatment. Cataract occurred in 6 of 12 eyes and good vision was preserved in 5 of 10 eyes in which function could be evaluated.

Child, Preschool

Specific identification of human ribonucleases by antibodies produced against two synthetic peptides corresponding to the N- and C-terminal amino-acid sequences of human urinary secretory-type ribonuclease.

Antibodies were raised in rabbits by immunizing two synthetic peptides, which corresponded to the N- and C-terminal 15 residues, respectively, of human urinary secretory ribonuclease (RNase). These antibodies did not block the RNase activity, but reacted well with enzymes blotted onto a transfer membrane following electrophoresis, and discriminated strictly between secretory- and nonsecretory-type RNases. Therefore, these antibodies should to be valuable tools for the immunological identification of human RNases.

Amino Acid Sequence

[Evaluation of thermal damage after hyperthermia on murine experimental tumor by 31P-NMR spectroscopy--correlation between ATP and growth curve].

The possibility of using 31P-NMR spectroscopy (31P-MRS) to estimate the effect of hyperthermic treatment on mouse FM3A tumor was investigated. 1 x 10(6) cells, suspended in saline, were subcutaneously inoculated to the right thigh of C3H mice. For hyperthermic treatment, the tumor-bearing leg was heated by immersing it in a water bath at 44 degrees C for 10, 20 or 30 min. The signal intensities of ATP and Pi of the tumor were measured utilizing the 31P-MRS technique to calculate the ATP/Pi ratio. Immediately after heating, the ATP/Pi ratio decreased markedly. Eighteen hours after hyperthermic treatment, the ratio recovered but was still smaller than the control value, then became almost constant by 24 hours after heating. The ATP/Pi ratio at 24 hours after heating decreased with increased length of heating and was inversely related to tumor regrowth after hyperthermic treatment. We concluded that non-invasive monitoring with 31P-MRS might provide a good indication of the effect of hyperthermic treatment.

Adenosine Triphosphate

Destructive arthritis without lymphocyte infiltration in H2-c-fos transgenic mice.

H2-c-fos transgenic (c-fos+) mice are characterized by the inability to raise specific IgG antibodies against immunizing Ag. To examine the contribution of Ag-specific IgG antibody to the development of arthritis, Ag-induced arthritis was produced in c-fos+ mice and their control littermates (c-fos- mice). Intra-articular injection of OVA into c-fos- mice hyperimmunized with OVA induced destructive arthritis with massive lymphocyte infiltration. The c-fos+ mice also developed destructive arthritis comparable in degree with that seen in c-fos- mice. However, joints from the c-fos+ mice had few or no infiltrating lymphocytes. The majority of cells invading the extensively eroded collagenous tissue in the c-fos+ mice had a mesenchymal appearance. These cells, producing excess amounts of c-Fos protein, adhered to and invaded the cartilage matrix when cultured on cartilage slices. These cells, thus, appear to directly cause joint destruction in c-fos+ mice.

Animals