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T Ikawa

Publications and source records attributed to T Ikawa.

17 recordsLinked to original sources

Electron microscopic observation of killer cells induced by mixed culture of lymphocytes with autologous cancer cells and further culture with recombinant interleukin-2.

Peripheral blood lymphocytes obtained from 2 patients with hypopharyngeal cancer were cultured with mitomycin C treated autologous tumor cells (autologous MLTC) for 10 days and further cultured with recombinant interleukin 2 (rIL-2). In one case 10-day MLTC induced increase of CD25-positive lymphocyte count, indicating that IL-2 receptors were expressed dominantly by the autologous tumor stimulation, and further culture with rIL-2 differentiated killing activity against autologous tumor cells. In the other case, however, MLTC alone induced killing activity against autologous tumor cells, indicating that the tumor cells from this patient might possess stimulatory activity sufficient to induce mature killer cells. Electron microscopic observation of the morphological features of lymphocytes cultured for 10 days revealed mostly small lymphocytes with low incidence of cytoplasmic granules. Further culture with rIL-2, however, induced slightly larger lymphocytes with well-developed microvilli, and cytoplasmic granules were found in many of the cells. Lymphokine activated killer (LAK) cells induced by culture of lymphocytes with rIL-2 alone were much larger and had long microvilli and abundant cytoplasmic granules, and were apparently morphologically different from the killer cells initiated by MLTC. The small lymphocytes induced by autologous MLTC alone might be autologous tumor specific cytotoxic T lymphocytes (CTL) and/or CTL precursors. Further culture with rIL-2 induced maturation of the CTL. However, the nature of the cytoplasmic granules remains obscure.

Antigens, CD

Polyenthesitis.

We described the clinical symptoms and signs of 11 cases of polyenthesitis, confirmed by the presence of inflammation in biopsies and increased activity in scintigraphy. All cases are negative for HLA-B27, and there is no presence of systemic inflammatory reaction, radiographic sacroiliitis, or chronic arthritis. The enthesitis is not ossifying and follows a rather benign clinical course. In one case, herpes virus-like particles were detected in the fibroblast debris of the tissue removed from Achilles tendon insertion. This fact suggests that polyenthesitis may be a clinical manifestation due to a reaction to an infectious agent.

Adolescent

Killer cells induced by stimulation with allogeneic tumor cells and subsequent culture with recombinant interleukin-2.

Peripheral blood lymphocytes were cultured for 5 days with allogeneic tumor cells (allogeneic mixed lymphocyte/tumor cell culture), and subsequently cultured with recombinant interleukin-2 for 12 days. These cultured cells were found to be cytotoxic to autologous tumor cells. Results of two-color analysis using monoclonal antibodies to cell markers showed that more than 80% of their cultured cells were CD3+ cells, and CD4+ cells showed a higher distribution than CD8+ cells. However, CD8+ cells had a much higher killing activity with autologous tumor than did CD4+ cells, when estimated by an elimination study using monoclonal antibodies to T cell phenotypes and complement. The "cold-target" inhibition test showed that the cytotoxicity of these cells for autologous tumor cells was inhibited by unlabeled autologous tumor cells but not by unlabeled stimulator cells. Furthermore, about 40% of the cytotoxicity was suppressed by blocking of HLA class I antigen with a monoclonal antibody on autologous tumor cells. Thus, cytotoxic activity of lymphocytes to autologous tumor restricted by target cell HLA class I antigen is possibly induced by allogeneic tumor-stimulation.

Adenocarcinoma, Papillary

Orientation of mineral in bovine bone and the anisotropic mechanical properties of plexiform bone.

Angular dependent Young's modulus E phi presented by Bonfield and Grynpas [Nature 270, 453-454 (1977)] was simulated by using the distribution function of the orientation of mineral in plexiform bone introduced on the basis of an X-ray pole figure analysis (XPFA) and a small angle X-ray scattering (SAXS) results. Calculations were performed with the aid of a simple model which expresses well the geometrical characteristic of plexiform bone. Estimated angular dependent Young's modulus in terms of the distribution of mineral orientation reproduced the experimental results. The suitable aspect ratio of bone mineral for the reproduction of the empirical data was a reasonable value compared with the morphological study of bone mineral. It is concluded that the angular dependence of mechanical properties of plexiform bone is explained by the distribution of bone mineral orientation and its morphology.

Animals

Autologous mixed lymphocyte reaction in head and neck cancer.

The proliferative response of T cells cultured with autologous non-T cells is known as the autologous mixed lymphocyte reaction (AMLR). The AMLR in patients with head and neck tumors was found to be significantly decreased in comparison with that in normal donors and patients without evidence of recurrent disease more than 3 years after treatment. Responder T cells in AMLR were CD4+ T cells but not CD8+ T cells. In one patient, AMLR were performed between lymphocytes in condition with tumor burden and those in condition with tumor free by using cryopreserved lymphocytes. T cells in tumor burden state poorly responded to both of these non-T cells. On the other hand, T cell in tumor free state vigorously responded to non-T cells in the same state, but not to non-T cells in tumor burden state. These data indicated that impairment of AMLR in patients with cancer was due to deficit of both responder T cells and autologous stimulator non-T cells.

Aged

Orientation of bone mineral and its role in the anisotropic mechanical properties of bone--transverse anisotropy.

An orientation of hydroxyapatite (HAP) crystals in bovine femur mineral was investigated by means of X-ray pole figure analysis (XPFA). It was found that the c-axis of HAP generally orients parallel to the longitudinal axis of bone (bone axis) and a significant amount of c-axis was oriented in other directions, in particular, perpendicular to the bone axis. Comparing these results with those of the small angle X-ray scattering (SAXS) investigation by Matsushima et al. (Jap. J. appl. Phys. 21, 186-189, 1982) at least two types of morphology of bone mineral were found; rod like bone mineral having the c-axis of HAP crystal parallel to the longitudinal axis of the rod and that having the c-axis not parallel, in a particular case, perpendicular to its longitudinal axis. Transverse anisotropy in mechanical properties of bone was reproduced by the estimation of Young's moduli by using the structural results mainly from XPFA. It is concluded that the anisotropy in mechanical properties of bone is well explained by taking account of the non-longitudinal (off-bone) axial distribution of orientation of bone mineral.

Animals

[Adoptive immunotherapy by intra-arterial infusion of ATLAK or Allo-TLAK cells in patients with head and neck cancer].

For clinical application of adoptive immunotherapy, it is necessary to prepare a sufficient number of autologous tumor specific effector cells. A large amount of peripheral blood lymphocytes was obtained by leukapheresis using a Heamonetics V50 pheresis system. Autologous tumor- and lymphokine-activated killer (ATLAK) cells were induced by autologous mixed lymphocyte tumor cell culture (autologous MLTC) and further activation with recombinant interleukin-2 (rIL-2). Another problem was the difficulty of obtaining a sufficient number of highly activated effector cells to reach the target tumor tissue. Direct infusion of effector cells into a feeding artery was effective for cell accumulation in the target. ATLAK cells were infused into maxillary artery in 4 patients with maxillary squamous cell carcinoma. The results indicated that the therapy was effective for reduction of the tumor mass. After immunotherapy, surgery was performed and the tissues were histologically examined. Degenerated tumor cells and intensive infiltration by mononuclear cells and macrophages were seen in the surrounding fibrous tissue. However, the quantity of fresh autologous tumor cells available from open biopsy was limited. Allogeneic cultured tumor cell line was used as stimulator of lymphocytes instead of autologous tumor cells. The killing activity of the allogeneic tumor and lymphokine activated killer (Allo-TLAK) cells was significantly induced against the autologous tumor cells. Antitumor effect was observed in 5 out of 9 patients. Side effects were minor, such as slight fever and blood eosinophilia, which may be due to the rIL-2 function. These results indicate that this method of therapy is an effective form of adoptive immunotherapy.

Adult

Suppressor cells in the effector phase of autologous cytotoxic reactions in cancer patients.

Cytotoxicity was induced in lymphocytes (CL) from 10 out of 15 patients by autologous mixed lymphocyte tumor cell culture and further cultivation with recombinant interleukin-2. In cells from 3 of the 10 patients, cytotoxicity was suppressed by more than 50% when autologous peripheral blood mononuclear cells (PBMC) from the patients with large tumors were added to the autologous killing system. The cells responsible for suppressing the cytotoxicity in the effector phase were adherent or nonadherent to plastic depending on the patient examined. The T cell fraction from 1 patient significantly suppressed the cytotoxic activity, and this suppression was seen only in the autologous system. On the other hand, plastic adherent cells but not T cells from PBMC of 2 subjects suppressed the cytotoxic activity of CL. The reason why the main cell population suppressing the CL activity differed among the patients is unclear. However, the findings that the suppression was mostly abrogated following resection of the tumor mass suggested that suppressor cells, either of macrophage lineage or T cells, are induced in patients with a large tumor mass. This speculation is supported by the finding that the PBMC from a patient with tumor recurrence regained the suppressive activity.

Aged

Autologous immune response of tonsillar lymphocytes.

Tonsillar (TL) and peripheral blood lymphocytes (PBL) from patients with pustulosis palmaris et plantaris (PPP) or recurrent tonsillitis (RT) were analysed for their proliferative response of T-cells upon stimulation with non-T-cells in the autologous mixed lymphocyte reaction (AMLR). TL and PBL from the same donor were cultured in the AMLR for up to 7 days. Maximum proliferation was observed after a 6-day culture in PBL, whereas that of TL was observed on the 3rd day of the culture. It was also observed that the AMLR of TL in patients with PPP was significantly (p less than 0.01) lower than in patients with RT. On the other hand, it has previously been proved by an immunofluorescence study that there is an identical antigenicity between tonsillar epithelium and skin. From this result, a blastoid transformation study of TL and PBL from patients with PPP was performed by using homologous or autologous skin extracts. Both homologous and autologous skin extract induced blastoid transformation of TL but PBL scarcely responded. These results may support the opinion that an auto-immunological mechanism may take part in the onset of PPP.

Foot Dermatoses

Adoptive immunotherapy for head and neck cancer with killer cells induced by stimulation with autologous or allogeneic tumour cells and recombinant interleukin-2.

Peripheral blood lymphocytes drawn by leukapheresis using Haemonetics V50 were mixed and cultured with autologous or allogeneic tumour cell line to activate killer cells by tumour antigenic stimulation, and further with recombinant interleukin-2 (rIL-2). Killer cells were intra-arterially infused, as a primary therapy, in 5 patients with maxillary and one with lingual cancer (squamous cell carcinoma). Effects on reduction of primary tumour size were significantly high without any severe side effects. The effects were interpreted mainly by direct day-by-day observation of the site, findings of CT and histology. Histological findings of the tissue obtained by surgical operation performed after adoptive immunotherapy were remarkable changes, such as infiltration of lymphoid cells around the cancer nets, degeneration of cancer cells, infiltration of scavenger macrophages (giant cells) and so on. The results suggested that adoptive immunotherapy by the killer cells can be a powerful treatment to bring the cancer under control, in with combination of other therapies.

Adult