Brain Metastasis of Pleural Mesothelioma after a Subarachnoid Hemorrhage.

Malignant pleural mesothelioma (MPM) is an uncommon, fatal neoplasm induced by asbestos exposure. Brain metastases from MPM are extremely rare, with most such cases diagnosed only at the time of autopsy. This report describes what we believe to be the first case of MPM metastasizing to the brain after a subarachnoid hemorrhage, as well as the subsequent surgical removal of the brain metastasis.

Pupil-sparing oculomotor nerve palsy caused by upward compression of a large posterior communicating artery aneurysm. Case report.

A 69-year-old woman without diabetes or hypertension presented with a large posterior communicating artery aneurysm projecting beneath the oculomotor nerve manifesting as a 2-week history of progressive diplopia. Neurological examination revealed external ophthalmoplegia and blepharoptosis without pupil involvement. Neuroimaging showed a large aneurysm in the left internal carotid artery projecting postero-inferiorly. Craniotomy and neck clipping of the aneurysm revealed the origin at the junction of the internal carotid artery and posterior communicating artery, and elevation of the oculomotor nerve. Pupil-sparing oculomotor nerve palsy is often assumed to be caused by ischemic injury such as hypertension and diabetes mellitus. Sometimes compressive lesion can cause pupil-sparing oculomotor nerve palsy with a short interval from the onset of symptoms to diagnosis. Despite the 2-week interval from the onset of symptoms, this patient presented with pupil-sparing oculomotor nerve palsy caused by compressive lesion. Involvement or sparing of the pupil is often considered to be the most important criterion in the diagnosis of isolated oculomotor nerve palsy. This unique case demonstrated that unusual compressive lesions must be taken into consideration in the diagnosis of pupil-sparing oculomotor nerve palsy.

Treatment of Parkinson's disease model mice with allogeneic embryonic stem cells: necessity of immunosuppressive treatment for sustained improvement.

OBJECTIVE: The purpose of the present study was to examine the efficacy of transplantation of mouse embryonic stem (ES) into Parkinson's disease (PD) model mice as well as the necessity of immunosuppression in allogeneic donor-host combinations. MATERIALS AND METHODS: ES cells, derived from SvJ129 strain mice, were differentiated into tyrosine hydroxylase (TH)-positive neurons in vitro by an embryoid body (EB)-based multistep differentiation method and used as graft cells for PD mice, which were prepared by injection of 6-hydroxydopamine (OHDA) into C57BL/6, BALB/c and C3H/HeN strains. Mice from each strain were divided into Groups 1-3. Four weeks after the 6-OHDA injection, Group 1 received phosphate-buffered saline in the striatum wounds, while Group 2 received 2 x 10(4) graft cells, and Group 3 mice received 2 x 10(4) graft cells and were also treated with cyclosporine A. RESULTS: Apomorphine-induced rotational behavior was improved in Groups 2 and 3, but not in Group 1. However, the behavioral improvement ceased later in Group 2, whereas sustained improvement was observed in Group 3 throughout the 8 week observation period after transplantation. ES-derived TH(+) cells were found at the grafted sites at the end of the experiment in Groups 2 and 3, and tended to be more abundant in Group 3. CONCLUSION: Intra-striatum transplantation of ES-derived dopaminergic neurons was effective in treating PD mice, even in allogeneic donor-host combinations. Immunosuppressive treatment did not have an effect on initial behavioral restoration after transplantation; however, it was necessary for sustained improvement over a prolonged period.

Cotransplantation of mouse embryonic stem cells and bone marrow stromal cells following spinal cord injury suppresses tumor development.

Embryonic stem (ES) cells are a potential source for treatment of spinal cord injury (SCI). Although one of the main problems of ES cell-based cell therapy is tumor formation, there is no ideal method to suppress tumor development. In this study, we examined whether transplantation with bone marrow stromal cells (BMSCs) prevented tumor formation in SCI model mice that received ES cell-derived grafts containing both undifferentiated ES cells and neural stem cells. Embryoid bodies (EBs) formed in 4-day hanging drop cultures were treated with retinoic acid (RA) at a low concentration of 5 x 10(-9) M for 4 days, in order to allow some of the ES cells to remain in an undifferentiated state. RA-treated EBs were enzymatically digested into single cells and used as ES cell-derived graft cells. Mice transplanted with ES cell-derived graft cells alone developed tumors at the grafted site and behavioral improvement ceased after day 21. In contrast, no tumor development was observed in mice cotransplanted with BMSCs, which also showed sustained behavioral improvement. In vitro results demonstrated the disappearance of SSEA-1 expression in cytochemical examinations, as well as attenuated mRNA expressions of the undifferentiated markers Oct3/4, Utf1, Nanog, Sox2, and ERas by RT-PCR in RA-treated EBs cocultured with BMSCs. In addition, MAP2-immunopositive cells appeared in the EBs cocultured with BMSCs. Furthermore, the synthesis of NGF, GDNF, and BDNF was confirmed in cultured BMSCs, while immunohistochemical examinations demonstrated the survival of BMSCs and their maintained ability of neurotrophic factor production at the grafted site for up to 5 weeks after transplantation. These results suggest that BMSCs induce undifferentiated ES cells to differentiate into a neuronal lineage by neurotrophic factor production, resulting in suppression of tumor formation. Cotransplantation of BMSCs with ES cell-derived graft cells may be useful for preventing the development of ES cell-derived tumors.

Cotransplantation of Mouse Embryonic Stem Cells and Bone Marrow Stromal Cells following Spinal Cord Injury Suppresses Tumor Development.

Embryonic stem (ES) cells are a potential source for treatment of spinal cord injury (SCI). Although one of the main problems of ES cell-based cell therapy is tumor formation, there is no ideal method to suppress tumor development. In this study, we examined whether transplantation with bone marrow stromal cells (BMSCs) prevented tumor formation in SCI model mice that received ES cell-derived grafts containing both undifferentiated ES cells and neural stem cells. Embryoid bodies (EBs) formed in 4-day hanging drop cultures were treated with retinoic acid (RA) at a low concentration of 5 × 10-9 M for 4 days, in order to allow some of the ES cells to remain in an undifferentiated state. RA-treated EBs were enzymatically digested into single cells and used as ES cell-derived graft cells. Mice transplanted with ES cell-derived graft cells alone developed tumors at the grafted site and behavioral improvement ceased after day 21. In contrast, no tumor development was observed in mice cotransplanted with BMSCs, which also showed sustained behavioral improvement. In vitro results demonstrated the disappearance of SSEA-1 expression in cytochemical examinations, as well as attenuated mRNA expressions of the undifferentiated markers Oct3/4, Utf1, Nanog, Sox2, and ERas by RT-PCR in RA-treated EBs cocultured with BMSCs. In addition, MAP2-immunopositive cells appeared in the EBs cocultured with BMSCs. Furthermore, the synthesis of NGF, GDNF, and BDNF was confirmed in cultured BMSCs, while immunohistochemical examinations demonstrated the survival of BMSCs and their maintained ability of neurotrophic factor production at the grafted site for up to 5 weeks after transplantation. These results suggest that BMSCs induce undifferentiated ES cells to differentiate into a neuronal lineage by neurotrophic factor production, resulting in suppression of tumor formation. Cotransplantation of BMSCs with ES cell-derived graft cells may be useful for preventing the development of ES cell-derived tumors.

CoCl(2) inhibits neural differentiation of retinoic acid-treated embryoid bodies.

The effects of CoCl(2) on retinoic acid (RA)-treated embryoid bodies (EBs) were investigated. Four-day EBs were treated with 5x10(-6) M of RA for 4 d, then subjected to attached culturing for 7 d in the presence of CoCl(2) at 0, 20, and 100 microM. Differentiation into MAP2- and GFAP-immunopositive cells was inhibited by CoCl(2) in a dose-dependent manner. Next, RA-treated EBs were dissociated into single cells and cultured for 7 d at an initial cell density of 1x10(3)/cm(2). The number of cells increased in a CoCl(2)-dose dependent fashion. In cultures with 100 microM of CoCl(2), more than 90% of the cells were immunopositive for nestin and nestin-immunopositive cells formed clusters, while there were few cells immunopositive for MAP2 or GFAP. These results suggest that CoCl(2) inhibits neural differentiation of RA-treated EB cells and promotes the proliferation of nestin-immunopositive cells, i.e., embryonic stem (ES)-derived neural stem-like cells.