Antisense-mediated reduction in thrombospondin-1 expression reduces cell motility in malignant glioma cells.

Thrombospondin-1 (TSP-1) is a multifunctional matrix protein implicated in cancer cell adhesion, migration, invasion, inhibition of angiogenesis and activation of latent transforming growth factor-beta. The involvement of TSP-1 in the motility of malignant glioma cells was investigated by transfection of TSP-1 complementary deoxyribonucleic acid (cDNA) sense and antisense expression vectors into the glioblastoma cell line T98G-G7 that secretes high amounts of TSP-1. TSP-1 production in the 3 antisense cDNA-transfected clones was significantly reduced to 51%, 43% and 47% compared to the host T98G-G7 cells. Motility of the 3 clones was evaluated by invasion assay and compared to the motility of host T98G-G7 cells and 2 sense-transfected clones. Migration of cells was significantly reduced in the 3 antisense-transfected clones with reduced TSP-1 production to 56%, 61% and 43% compared to the host T98G-G7 cells. The host T98G-G7 and another TSP-1-secreting A172 and YMG5 glioblastoma cells were also treated with a synthetic peptide, WSHWSPWSSCSVTCG, which includes 3 consecutive sequences of the adhesion sites in the TSP-1 molecule and with a control peptide. The synthetic peptide significantly inhibited the migration of T98G-G7 and A172 cells in a dose-related manner. Maximum inhibition of migration was achieved by 100 microg/ml of the peptide and the reduction of cell motility compared to untreated cells was 34.6 % and 53.9 %, respectively. On the other hand, the inhibition of migration by the peptide was minimal in YMG5 cells, which secretes a smaller amount of TSP-1 than T98G-G7 and A172 cells. These results suggest that TSP-1 secreted by malignant glioma cells is involved in the motility of glioma cells.

Participation of thrombospondin-1 in the activation of latent transforming growth factor-beta in malignant glioma cells.

Malignant glioma cells secrete transforming growth factor-beta (TGF-beta) and can activate latent TGF-beta. However, the mechanism of the latent TGF-beta activation has not yet been determined. This study examined whether thrombospondin-1 (TSP-1) secreted by malignant glioma cell lines participates in the activation of latent TGF-beta secreted by the glioma cells. Western blot analysis revealed that TSP-1 was present in both the cell lysates and the culture supernatants of all three malignant glioma cell lines (T98G, A172, and U251). A bioassay for TGF-beta activity revealed that all malignant glioma cell lines used in this study could activate latent TGF-beta by themselves. Latent TGF-beta 1 activation, evaluated by enzyme-linked immunosorbent assay, was inhibited by more than 50% by the addition of neutralizing anti-TSP-1 monoclonal antibody or anti-TSP-1 polyclonal antibody. These results indicate that TSP-1 has a predominant role in the activation of latent TGF-beta in malignant glioma cells.

Focal hyperperfusion in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. Case report.

A 28-year-old woman presented with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). The diagnosis was based on the results of molecular genetic analysis, which indicated a typical point mutation at the nucleotide pair 3243. Xenon computerized tomography scans obtained during the strokelike episodes revealed the lesion responsible for the symptoms to be an area of focal hyperperfusion, and scans obtained after the episodes revealed an area of hypoperfusion. Pathogenesis of the strokelike episodes appears to be metabolic dysfunction, although the involvement of a vascular event cannot be excluded.

Serial angiography and endovascular treatment of dissecting aneurysms of the anterior cerebral and vertebral arteries. Case report.

This 47-year-old man was admitted to the hospital with disturbance of consciousness due to subarachnoid hemorrhage caused by a ruptured dissecting aneurysm of the left anterior cerebral artery (ACA). Conservative treatment resulted in improvement in the patient's consciousness; however, repeated rupture occurred during the chronic stage. Endovascular coil embolization of the parent artery was successful. Serial angiography demonstrated all stages in the development of the aneurysm. Follow-up angiography demonstrated an incidental dissecting aneurysm of the right vertebral artery. This aneurysm was also treated by endovascular embolization. No new neurological deficit appeared during or after the treatment. Multiple dissecting aneurysms are rare, especially those involving both supra- and infratentorial regions. A ruptured dissecting aneurysm of the ACA is also an uncommon vascular disorder. This case shows that rebleeding may occur, even during the chronic stage, and thus appropriate treatment for the prevention of subsequent bleeding is essential. Incidental dissecting aneurysms can be treated using the endovascular technique, but further study is necessary.

Recurrence of medulloblastoma 19 years after the initial diagnosis.

A 25-year-old woman presented with recurrent medulloblastoma. She had been diagnosed with cerebellar medulloblastoma and treated for it at the age of 5 years. The new tumor was partially resected and chemotherapy was begun. However, a disseminated tumor of the spine was discovered and, despite radiotherapy, the patient became comatose and died. Histological examination of the tumor specimen showed characteristics similar to those of the first tumor. Late recurrence of medulloblastoma is rare, and a latency period of 19 years is the longest reported. This case violates Collins' rule and exceeds other proposed periods of risk. Extension of the period of follow-up in patients with medulloblastoma is advocated.

Malignant intravascular lymphomatosis associated with venous stenosis. Case report.

This 55-year-old man presented with malignant intravascular lymphomatosis, a rare vascular disorder of the central nervous system characterized by proliferation of malignant lymphoma cells. The clinical manifestations were focal neurological signs and progressive dementia. Angiography demonstrated stenoses of the cortical veins. Postmortem examination revealed infiltration of tumor cells into the lumen and vascular wall, although the stenoses were caused primarily by fibrin thrombi. To the authors' knowledge this is the first case of malignant intravascular lymphomatosis associated with venous stenosis.

Visual recovery following immediate decompression of traumatic retrobulbar hemorrhage via transcranial approach.

A 17-year-old boy presented with retrobulbar hemorrhage manifesting as right proptosis, periorbital swelling, and blindness after suffering a midfacial trauma. Immediate decompression by removal of the retrobulbar hemorrhage via the transcranial approach was performed. The proptosis was resolved and visual acuity and eye movement were restored. Retrobulbar hemorrhage is a serious injury which may lead to blindness. However, recovery from blindness can be achieved with adequate management including neurosurgical decompression in the early stage.

Kidney transplantation and liaison psychiatry, part I: anxiety before, and the prevalence rate of psychiatric disorders before and after, transplantation.

We examined psychiatric problems before and after kidney transplantation in a sample of 36 patients with end-stage renal failure. The prevalence rate of psychiatric disorders was 11.1% (4 of 36 cases) before the transplantation and 36.1% (13 of 36 cases) within 2 months after the transplantation. Except for a patient with schizophrenic disorder, no patients were found to have a psychiatric disorder from 2 to 6 months after the transplantation. In this study, we also examined anxieties and/or conflicts related to the transplantation using the synthetic house-tree-person (HTP) drawing test, a measure of mood states by means of a non-verbal expression method. The upper part of the tree trunk was not drawn in 25% of this sample (5 of 20 cases). In the HTP drawing tests immediately after the transplantation, however, trees missing the upper part of trunk were not drawn. Based on these findings, we discussed psychiatric problems in kidney transplantation.