Matsui Y

An adoptive immunotherapy of patients with medulloblastoma by lymphokine-activated killer cells (LAK)

SummaryAn adoptive immunotherapy of 6 patients with medulloblastoma by lymphokine-activated killer (LAK) cells is described. They were from 2 to 9 years in age and had cerebrospinal fluid (CSF) dissemination of the tumours. All patients underwent the whole-neuraxis irradiation and chemotherapy. After the usual treatments, they were submitted to an adoptive transfer of one-haplotype identical LAK cells. The LAK cells were induced from peripheral blood lymphocytes (PBL) of their relatives with human recombinant interleukin-2 (rIL-2). 3–15×109 LAK cells were transferred intrathecally in 2–3 months. In 3 of 6 patients, neurological signs were improved and malignant cells had never been detected on CSF cytology after the adoptive immunotherapy. One among these 3 patients showed complete response in 20 months. Thus, this is an attractive approach for the treatment of medulloblastoma with CSF dissemination of the tumour which current therapeutic intervention can not cure.

[Effects of phenytoin on cell-mediated immunity].

SummaryThe effects of phenytoin on cellular immunity were examined in murine models. Fresh splenocytes were obtained from mice which had received 1 mg/day of phenytoin i.p. for 28 days. The serum concentration of phenytoin in these animals was 10–10 μg/ml. The proliferative response of splenocytes to mitogens was assessed by 3H-thymidine incorporation. The cytotoxic activities of cells such as natural killer (NK) cells, cytotoxic T lymphocytes (CTL), and lymphokine-activated killer (LAK) cells were estimated by a 4-h 51Cr release assay. The 3H-thymidine incorporation of splenocytes was reduced significantly (P<0.01) in phenytoin-treated mice. The NK and CTL activities of splenocytes from phenytoin-treated mice were significantly suppressed. However, the LAK activity of phenytoin-treated mice was equal to that of control mice.

Neural transplantation in mouse Parkinson's disease.

A complete recovery from the methamphetamine-induced rotational response was shown in C57BL/6 (H-2b) mice which had had unilateral 6-OHDA lesions in the nigrostriatal pathway about 60 days after transplantation of approximately 1 x 10(6) dopamine-rich cells from syngeneic or allogeneic (C3H/HeN, H-2k) mouse embryos (ED 15), without immunosuppressive agents. Morphological examination showed tyrosine-hydroxylase-immunoreactive cell clusters around the needle tract in the mice which were transplanted not only with syngeneic cells but also with allogeneic cells. This might indicate that so-called immunosuppressive agents are not necessary for grafted embryonic cells to survive in an allogeneic mouse brain.

Transplant-induced Recovery from 6-OHDA Lesions of the Nigrostriatal Dopamineneurones in Mice

Attempts to reconstruct the damaged nigrostriatal pathway in experimental models of Parkinsons disease have thus far been carried out in animals with neurotoxically induced dopamine deficiency. Our study established that unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopamine (DA) neurons produced a well-characterized functional asymmetry in the behaviour of the C57BL/6 (H-2b) mice. The intraperitoneal administration of methamphetamine induced ipsilateral rotation at 7-20 turns/min 1 x 10(6) syngenic DA-rich cells of embryonic ventral mesencephalon were stereotaxically transplanted in the caudate-putamen. A complete recovery of methamphetamine-induced rotational response was produced around the 60th day after the syngenic cell suspension graft. And a complete compensation of the rotational response was also brought about with the DA-rich cells from embryonic ventral mesencephalon (crown-rump length; 10-13 mm) of allogenic C3H/HeN (H-2k) mice. The FACS IV analysis revealed no H-2 (Kk and Iak) antigens before transplantation of these embryonic cells. Immunohistochemistry showed that the dopaminergic fibers had grown predominantly into the ipsilateral caudate-putamen. These results provide evidence of integration of syngenic and allogenic grafts and host tissue. And the immunological response in the transplanted brain are under investigation.

Bilateral Traumatic Carotid-cavernous Fistulas

A case of bilateral traumatic carotid-cavernous fistulas (CCFs) is reported. A 39-year-old man had fractures in the skull base and facial bones from a traffic accident. Several days later he had a pulsating proptosis, chemosis, and bruit in both eyes. Neurological examination on admission revealed right-sided blindness due to optic nerve injury. Cerebral angiograms demonstrated bilateral traumatic CCFs with large openings, and steal phenomenon of blood flow. Endarterial balloon catheterization with iodine contrast material was performed twice on the right side and once on the left side but failed. Subsequently the patient suffered from right retro-orbital pain and left blurred vision. A big venous pouch (or false aneurysm) occurred in the cavernous portion of the right carotid artery. The left CCF remained open with venous drainage to the cavernous sinus and superior ophthalmic vein, which resulted in left retinal congestive bleeding. The right venous pouch was treated by occlusion of the internal carotid artery with detachable balloons and external carotid artery to middle cerebral artery bypass with venous graft. The left CCF was treated again by detachable balloon with preservation of the internal carotid artery flow. Postoperative digital subtraction angiography revealed disappearance of bilateral CCFs. Problems of detachable balloon catheterization are discussed.

Investigation of MHC Antigens on Neural Graft in Mouse Parkinson’s Models

Parkinson’s disease is one of the most common disorders that affect the nigrostriatal system in human. Loss of neurons in the substantia nigra and severe depletion of dopamine (DA) in the corpus striatum are the hallmarks of this condition. The most effective treatment of Parkinson’s disease, particularly in its early phase, is the administration of both the L-isomer of 3,4-dihydroxyphenylalanine (L-DOPA) and dopamine-receptor agonists. However, it is clear that L-DOPA and the receptor agonists provide only limited ameliorable treatment and that most patients inexorably become progressively debilitated regardless of the type of therapy. On the other hand, an alternative approach in the therapeutic management of Parkinson’s disease is surgical implantation of either DA neurons or adrenal chromaffin cells that have the ability to release DA.1