Biomedical subjects

T Ishida

Publications and source records attributed to T Ishida.

At least 811 records · Page 45Linked to original sources

PubMed1991

Combination of Trp and Glu residues for recognition of mRNA cap structure. Analysis of m7G base recognition site of human cap binding protein (IF-4E) by site-directed mutagenesis.

Four mutants of the human cap binding protein (hCBP), in which Trp-102, Glu-103, Asp-104 or Glu-105 was changed to the aliphatic Leu or Ala, were prepared, and their cap binding abilities were examined. Cap binding abilities of two mutants, W102L (Trp-102----Leu) and E105A (Glu-105----Ala), were significantly decreased in comparison with the wild-type hCBP. This result suggests that Trp-102 and Glu-105 are both necessary for the cap binding, and the most probable binding mode with the m7G of cap structure is the combination of the stacking by Trp-102 and the hydrogen-bond pairing by Glu-105, as was already proposed from the model studies.

Amino Acid Sequence↗

PubMed1991

Distinct mechanisms of neonatal tolerance induced by dendritic cells and thymic B cells.

To assess the role of different types of antigen-presenting cells (APC) in the induction of tolerance, we isolated B cells, macrophages, and dendritic cells from thymus and spleen, and injected these into neonatal BALB/c mice across an Mls-1 antigenic barrier. One week after injection of APC from Mls-1-incompatible mice or from control syngeneic mice, we measured the number of thymic, Mls-1a-reactive, V beta 6+ T cells and the capacity of thymocytes to induce a graft-vs.-host (GVH) reaction in popliteal lymph nodes of Mls-1a mice. Injection of thymic but not spleen B cells deleted thymic, Mls-1a-reactive V beta 6+ T cells and induced tolerance in the GVH assay. The thymic B cells were primarily of the CD5+ type, and fluorescence-activated cell sorter-purified CD5+ thymic B cells were active. Injection of dendritic cells from spleen or thymus also induced tolerance, but the V beta 6 cells were anergized rather than deleted. Macrophages from thymus did not induce tolerance. Dendritic cells and thymic B cells were also effective in inducing tolerance even when injected into Mls-, major histocompatibility complex-incompatible, I-E- mice, but only thymic B cells depleted V beta 6-expressing T cells. Therefore, different types of bone marrow-derived APC have different capacities for inducing tolerance, and the active cell types (dendritic cells and CD5+ thymic B cells) can act by distinct mechanisms.

Animals↗

PubMed1991

Cytolytic potential of peripheral blood T-lymphocytes following adoptive immunotherapy with lymphokine-activated killer cells and low-dose interleukin 2.

In this study, we investigated the cytolytic activity of peripheral blood T-cells (PBT) obtained from nine patients with primary lung cancer treated by surgical adjuvant adoptive immunotherapy (AIT) with lymphokine-activated killer cells and low-dose recombinant interleukin 2 at the time of rebound lymphocytosis (24-48 h after AIT). In eight of nine patients, nonspecific cytotoxicity of peripheral blood lymphocytes significantly increased as compared with that of pre-AIT peripheral blood lymphocytes. However, purified PBT showed much less activity to kill tumor cells although they increased in number and were activated well in terms of increases in the expression of HLA-DR and interleukin 2 receptor. The cytolytic activity of post-AIT PBT was significantly enhanced when they were targeted to Fc receptor-bearing tumor cells (K562 or Daudi) with anti-CD3 (NU-T3) or anti-T-cell receptor (TCR)alpha beta (WT31) monoclonal antibody in all five patients examined. Phenotypically, the targeted cytotoxicity was predominantly mediated by CD8+ cells. The results indicated that in vivo-activated PBT by AIT could not exhibit direct cytotoxicity, but they acquired cytolytic potential, the effect of which was expressed by targeting to tumor cells.

Aged↗

PubMed1991

Surgical resection of pulmonary metastases from colorectal adenocarcinoma. Special reference to repeated pulmonary resections.

Pulmonary resection of metastatic lesions from colorectal adenocarcinoma was performed in 35 patients. The cumulative 5-year survival was 38%. The primary site of cancer was the colon in about half of the patients. Patients with a solitary metastasis or tumors smaller than 3 cm in diameter survived longer than did patients with multiple metastases or tumors larger than 3 cm but the differences were not significant. Other factors, including age, sex, histologic grade of tumor, location and stage of primary carcinoma, location of pulmonary metastases, disease-free interval, and type of pulmonary resection, had no apparent influence on survival time. The lung was the major site of recurrence following pulmonary resection. Seven patients underwent two or more pulmonary resections for metastasis from a colorectal carcinoma. At the time of last follow-up, four patients were alive and free of recurrent disease at 5, 34, 39, and 58 months after the second pulmonary resection. These data suggest that some patients will survive for a long time following pulmonary resection of colorectal metastases, and for highly selected patients, repeated pulmonary resection may further extend survival.

Adenocarcinoma↗

PubMed1991

New assay to detect shedding antigen with use of anti-idiotypic monoclonal antibodies.

Anti-idiotypic (Anti-Id) monoclonal antibodies (MoAbs) against anti-carcinoembryonic antigen (CEA) monoclonal antibody 5B3 (IgG1) were prepared and characterized. Five anti-Id MoAbs recognized the private idiotype of MoAb 5B3. Idiotype mapping suggested that MoAb 5B3 had at least three distinct idiotopes at its antigen combining site. Utilizing the inhibition of idiotype-anti-idiotype interaction with use of anti-Id MoAb T4-305 or T4-212, an immunoassay to detect shedding CEA was established. The results of this inhibition assay correlated with those of double determinant immunoassay and inhibition percentages linearly increased in a CEA concentration-dependent manner. Since it requires only one epitope of a given antigen molecule, this assay could be widely used for detection of shedding antigens, including tumor-associated antigens.

Animals↗

PubMed1991

Molecular and crystal structures of 2-(2-pyridyl)thioacetamide derivatives and possible relationship with inhibitory activity for gastric acid secretion.

As a possible method to determine the key atoms and their spatial orientation which are necessary for the gastric mucosal protective and antisecretory activity, crystal structures of sixteen 2-(2-pyridyl) thioacetamide derivatives have been analyzed by the X-ray diffraction method. The characteristics of the molecular and crystal structures of the derivatives are described in this paper. The energetic stability of the molecular conformation is also investigated by means of the molecular force field method. Using the conformational data, a possible relationship between the stereostructure and inhibitory activity for gastric acid secretion is considered by QSAR analyses. The results suggest that the activity is related to the overall molecular conformation, and that the spatial distribution of the side-chain polar atoms with respect to the fixed pyridine is especially important for the activity.

Animals↗

PubMed1991

Studies of serum-free medium for the generation of lymphokine-activated killer cells.

We examined a serum-free medium (designated as TYI 101) for the generation of lymphokine-activated killer (LAK) cells from human lymphocytes, regional lymph node lymphocytes (RLNL) and peripheral blood lymphocytes (PBL). TYI 101 medium consisted of, in addition to nutrient mixture, transferrin, insulin, fetuin, sodium selenite, 2-mercaptoethanol, o-phosphorylethanolamine, chick egg yolk and porcine kidney extract. These hormones were effective for supporting RLNL proliferation as assessed by (3H)-thymidine uptake. When human lymphocytes from two different sources were cultivated with recombinant interleukin 2 (rIL-2) in TYI 101 medium, LAK activity was generated. In cultures of PBL from a healthy donor, LAK cells were generated in TYI 101 medium as efficiently as in RPMI 1640 medium supplemented with 10% human AB-type serum (RPMI-AB). In cultures of RLNL from lung cancer patients, LAK activity obtained in TYI 101 medium was about sixty-five percent of that in RPMI-AB. However, the addition of a small amount of AB-type serum improved the generation of LAK activity, LAK cell expansion, and cell viability in TYI 101 medium. We conclude that TYI 101 medium can be used for the generation of LAK cells from human lymph node lymphocytes with supplementation of none or only a reduced amount of human serum.

Animals↗

PubMed1991

Histological grading and morphometric analysis of cartilaginous tumours.

Morphometric analysis of cartilaginous tumours was performed on 25 chondrosarcomas, 9 cases of enchondroma (ENCH), and 2 chondroblastic osteosarcomas (CBOS). The chondrosarcomas were classified into three grades of malignancy according to Evans' histological classification and were further divided into low and high grades of malignancy. Cellularity, nuclear area, binucleate cells and mitotic figures were examined using formalin-fixed and paraffin-embedded specimens. The cellularity was significantly higher in high-grade chondrosarcoma (HGCS) than in low-grade chondrosarcoma (LGCS) (P less than 0.005). The nuclear area was larger in more malignant lesions. Significant differences in the nuclear area were found between ENCH and LGCS (P less than 0.005) and between LGCS and HGCS (P less than 0.01). Binucleate cells were found more frequently in LGCS than in ENCH (P less than 0.005). Although a few mitotic figures were found in HGCS, they were extremely rare in chondrosarcomas. Mitotic figures, however, were easily found in CBOS when compared with HGCS (P less than 0.05). These results suggest that nuclear area and binucleate cells are useful for differentiation between benign and malignant cartilaginous lesions and that easily detectable mitotic figures are a reliable marker for neoplastic cartilage in osteosarcoma.

Adolescent↗

PubMed1991

Clinical significance of tumor marker NCC-ST 439 in large bowel cancers.

We examined serum NCC-ST 439 for its significance as a tumor marker of large bowel cancer in 121 patients with primary and 36 with recurrent large bowel cancer. Serum NCC-ST 439 was positive in 27.3 percent of the former and 66.7 percent of the latter. It was false-positive in only 5.6 percent of patients with benign diseases. Positive serum NCC-ST 439 correlated with lymph node and liver metastases. The combination assay for NCC-ST 439, CEA, and CA19-9 was positive in 49.6 percent of the patients with primary tumors and 88.9 percent of those with recurrent tumors; in other words, the diagnostic accuracy improved. The results demonstrated that the determination of serum NCC-ST 439 in large bowel cancer might be useful in cancer staging and that NCC-ST 439, if used in combination with CEA, is particularly useful in diagnosing recurrences because of its improved diagnostic accuracy.

Antibodies, Monoclonal↗

PubMed1991

Investigation of colonic prostaglandins in carcinogenesis in the rat colon.

Large bowel carcinoma was induced in rats by injecting MNNG intrarectally, and changes in the large bowel mucosa prostaglandin (PG) with time were determined. The PGE2 levels of the colonic mucosa in a control group were 20.9 +/- 9.7 (pg/mg total protein) at 5 weeks, 25.5 +/- 9.7 at 10 weeks, 26.5 +/- 18.1 at 20 weeks, and 34.8 +/- 12.7 at 40 weeks. The PGE2 levels in the MNNG-treated group were 44.7 +/- 6.2 at 5 weeks, 43.1 +/- 14.9 at 10 weeks, 70.1 +/- 23.4 at 20 weeks, and 79.7 +/- 54.1 at 40 weeks. The intrinsic PGE2 levels of the noncancerous mucosa were thus significantly higher for the MNNG group than for the control group at all weeks. At 40 weeks, the PGE2 levels of cancer lesions were significantly high compared with those of the noncancerous area. In the cancerous lesions, 6-keto-PGF1 alpha and PGF2 alpha decreased and TXB2 increased significantly at 40 weeks. The observations demonstrated that PGE2 was implicated as a promoter in the development and proliferation of carcinoma in MNNG-induced large bowel carcinogenesis in rats.

Animals↗

PubMed1991

Detection by CT during arterial portography of colorectal cancer metastases to liver.

A prospective evaluation of the accuracy of real-time ultrasonography (US), computed tomography (CT), infusion hepatic angiography (IHA), and computed tomography during arterial portography (CT-AP) was performed on 65 resected liver metastases of colorectal cancers. The total detection rate was 58.5 percent for US, 56.3 percent for CT, 55.4 percent for IHA, and 86.2 percent for CT-AP. The sensitivity of 29 lesions with diameters of smaller than 1 cm was 65.5 percent for CT-AP, CT found only two, and both US and IHA localized no more than three. The smallest lesions detectable by CT-AP were as small as 0.4 cm in diameter. CT-AP proved most useful in detecting the liver metastases, and the use of this technique is recommended for preoperative planning of hepatectomy on patients with liver metastases.

Angiography↗

PubMed1991

A regimen of surgical adjuvant immunotherapy for cancer with interleukin 2 and lymphokine-activated killer cells. Basis, clinical toxicity, and immunomodulatory effects.

We designed a unique regimen of adoptive immunotherapy with lymphokine-activated killer (LAK) cells and recombinant interleukin 2 (rIL-2) for application with surgical adjuvant therapy of cancer. The regimen features the prolonged (6 consecutive days) s.c. administration of low-dose rIL-2 and the transfer of ex vivo generated LAK cells from regional lymph node lymphocytes, obtained at the time of surgical operation. According to this regimen, 5 patients with primary lung cancer received immunotherapy about 2 weeks after surgery (pulmonary lobectomy). Clinical toxicities included fever(5/5), fatigue(5/5), slight(less than 5%) weight gain(5/5), increase of pleural effusion at the lobectomy site(2/5), and edema formation(1/5). All toxicities reversed within 4 days after the completion of therapy. Rebound lymphocytosis after therapy ranged from 2.4 to 5.5-fold (mean, 4.3-fold) over the baseline. Peripheral blood lymphocytes obtained during this lymphocytosis exhibited in vitro LAK activity in 4 of 5 patients. Thus, the regimen is considered to be well-tolerable and immunologically active in regard to the postoperative state of the patients.

Adjuvants, Immunologic↗

PubMed1991

Clinical application of indium-111 antimyosin antibody and thallium-201 dual nuclide single photon emission computed tomography in acute myocardial infarction.

The significance of indium-111 antimyosin antibody and thallium-201 dual nuclide single photon emission computed tomography (SPECT) was evaluated in 7 patients with acute myocardial infarction (AMI) who underwent emergency coronary angiography with successful revascularization by intracoronary thrombolysis. Indium-111 antimyosin antibody and thallium-201 dual nuclide SPECT was performed 11 to 36 days after the onset of AMI. Antimyosin SPECT images delineated areas of myocardial necrosis in all 7 patients (100%), but planar images detected necrotic areas in only 4 of 7 patients (57%). Peak CPK-MBs of the 3 patients in which no necrotic area was detected by indium-111 planar image showed a tendency to be smaller. Indium-111 antimyosin antibody/thallium-201 overlap was observed in all patients. The area of overlap was at the center of necrosis in 4 patients (2 anterior infarction, 1 inferior infarction, 1 inferolateral infarction) and at the peripheral portion in 3 patients (all 3 had inferior infarction). Indium-111 antimyosin antibody and thallium-201 dual nuclide SPECT is useful in identifying the localization of myocardial infarction and the overlap of these tracers might reflect the presence of salvaged myocardium adjacent to the necrotic myocardium.

Aged↗

PubMed1991

Ontogeny of thymic B cells in normal mice.

Ontogeny of thymic B cells and their surface characteristics were analyzed using monoclonal antibodies (mAbs) against B220 molecules (CD45, CD45R). A small number of B cells were detected in fetal thymus on Gestation Day 14 (approximately 3.5% of the low-density fraction). Similarly, the percentage of B cells in the low-density fraction was 3.2% on Gestation Day 18, and 3.5% on Day 1 after birth. These were the same level as that of adult mice. CD5+ B cells, which form the major population of thymic B cells, were also found in the fetal life (0.5% on Day 14 and 2.2% on Day 16 in the low-density cells). The percentage of CD5+ B cells in B cell-enriched fraction was about 65% on Day 1 after birth, which is the same level as that in adult mice. These results indicate that a small number of B cells or cells in the B-cell lineage are present in the fetal thymus and also suggest the importance of these thymic B cells in the negative selection of T cells during early developmental stages.

Animals↗

PubMed1991

Prognostic value of c-erbB-2 protein expression in human lung adenocarcinoma and squamous cell carcinoma.

203 primary human lung tumours, of which 119 were adenocarcinoma and 84 were squamous cell carcinoma, were investigated immunohistochemically for the expression of c-erbB-2 protein. Positive staining was evident in 33 (28%) of adenocarcinomas and 2 (2%) of squamous cell carcinomas. In cases of adenocarcinoma, c-erbB-2 was present in 18% of those with stage I disease. In stage IIIA, stage IIIB and stage IV cases, c-erbB-2 was present in 39%, 50% and 60%, respectively (I vs. IIIA and I vs. IIIB: P less than 0.05, I vs. IV: P less than 0.01). The 5-year survival rates of c-erbB-2 positive patients and those who were negative were 30% and 52%, respectively, with a statistically significant difference (P less than 0.01). These observations suggest that when the expression of c-erbB-2 correlates with invasiveness of the tumour, this correlation may serve as a prognostic indicator, particularly in cases of adenocarcinoma of the lung.

Adenocarcinoma↗

PubMed1991

Integral laser photodynamic treatment of refractory multifocal bladder tumors.

Integral photodynamic therapy with hematoporphyrin derivative was performed on 35 patients who had resistant transitional cell carcinoma of the bladder, mainly carcinoma in situ. The light source was an argon ion pumped dye laser (wavelength 630 nm.) using rhodamine B. Two types of laser light scattering diffuser developed at our department were used: a motor driven laser light scattering diffuser with computer regulation, and an endoscope modified light scattering diffuser tipped with a small quartz bulb containing a lipid nutritious solution as the scattering medium. The total energy density used was 10 to 30 J./cm.2. Of the 35 patients 24 (68.6%) achieved a complete response and 5 (14.3%) a partial response at 3 months. In 10 of the 24 patients there was no recurrence with an average tumor-free interval of 20.9 +/- 16.7 months, ranging from 5 to 60 months. Bladder capacity was decreased to approximately 150 ml. for 3 months after the integral photodynamic therapy without any evidence of hydronephrosis on excretory urograms, except for 2 patients who had a contracted bladder before photodynamic therapy. Integral photodynamic therapy may prove to be useful for the treatment of carcinoma in situ of the bladder.

Adult↗

PubMed1991

Enhanced bioavailability of subcutaneously injected insulin by pretreatment with ointment containing protease inhibitors.

The present study was undertaken to develop an ointment preparation containing a protease inhibitor for stabilizing subcutaneously injected insulin. The ointment containing the protease inhibitor, gabexate mesilate or nafamostat mesilate, was applied to the skin around the insulin injection site. Three results were obtained. First, gabexate and nafamostat inhibited insulin degradation in subcutaneous tissue homogenates in vitro. Second, after application of gabexate or nafamostat ointment, an appreciable amount of gabexate or nafamostat appeared in the subcutaneous tissue of rats or hairless mice and their concentrations were comparable to those seen in the in vitro experiment. Third, insulin degradation at the subcutaneous injection site in the rat was depressed after pretreatment with gabexate or nafamostat ointment. Pretreatment with gabexate or nafamostat ointment increased the plasma immunoreactive insulin (IRI) levels and the hypoglycermic effect of insulin in healthy volunteers. These results indicate that gabexate or nafamostat ointments stabilize subcutaneously injected insulin.

Administration, Topical↗

PubMed1991

Prognostic implication of transforming growth factor alpha in adenocarcinoma of the lung--an immunohistochemical study.

We examined for transforming growth factor alpha (TGF alpha) in adenocarcinomatous lesions of the lung tissues excised from 138 patients, with use of the avidin-biotin-peroxidase complex (ABC) method. TGF alpha was present in the cytoplasm of the adenocarcinoma. Our objective was to determine if TGF alpha could serve as a prognostic parameter. We divided 138 patients into two groups according to the concentration of TGF alpha. Ninety-two patients had a high concentration of TGF alpha, in over 75% of the tumour cells, while 46 had a low concentration, that is in less than 75% of the cells. The 5-year survival rates of patients with high TGF alpha and low TGF alpha were 39% and 64%, respectively (P less than 0.05). Our data suggest that evidence of a high immunoreactivity of TGF alpha can serve as a prognostic parameter in adenocarcinoma of the lung.

Adenocarcinoma↗