Suprasellar hemangioblastoma in a patient with von Hippel-Lindau disease confirmed by germline mutation study: case report and review of the literature

BACKGROUND: Hemangioblastoma (HBL) in the suprasellar region is extremely rare.CASE DESCRIPTION: A suprasellar mass was found in a 33-year-old woman with retinal HBL and bilateral adrenal pheochromocytomas. The diagnosis of von Hippel-Lindau (VHL) disease was confirmed preoperatively not only by these clinical manifestations but also by germline mutation study. The existence of VHL disease indicated a diagnosis of HBL for the suprasellar mass. The results of our mutation study indicated that this patient had type II VHL disease, suggesting that careful follow-up is essential for the early detection of renal cell carcinoma, which is often associated with type II VHL disease. Here, we summarize the previously reported features of sellar and suprasellar HBLs.CONCLUSIONS: HBLs in this region may be one manifestation of VHL disease. Genetic testing of the VHL gene of our patient could provide useful information to determine appropriate medical care and management.     

ACNU, MTX And 5-FU Penetration of Rat Brain Tissue and Tumors

The distribution of radio-labeled ACNU, MTX and 5-FU in brain and tumor tissue was studied in female Wistar rats by macroautoradiography after intrathecal administration. In normal rats, ACNU and 5-FU, administered intracisternally, distributed rapidly in the subarachnoid space, ventricular system and cerebrospinal fluid (CSF). 5-FU and MTX penetrated the brain deeply; the diffusional transport of ACNU was limited to a depth of 1 or 2mm from the CSF surface of the brain. MTX and 5-FU clearance into the blood circulation was rather slow while ACNU cleared relatively quickly. The half time of ACNU, 5-FU and MTX radioactivity at the ventricular surface was 10, 21, and 110min, respectively, at their maximal concentration after intracisternal administration. In rats with leptomeningeal tumor induced by intracisternal inoculation of Walker 256 cells, the distribution patterns of ACNU, 5-FU, and MTX were essentially the same as in normal rats despite 10–20 cell layers of tumor growing in the subarachnoid space. 5-FU and MTX were able to penetrate tumor masses in the subarachnoid space; MTX penetration was slower than that of 5-FU and ACNU failed to penetrate to more than a depth of 1 or 2mm from the tumor surface.     

Analysis of aluminum hydroxyphosphate vaccine adjuvants by (27)Al MAS NMR

The present study explores the use of (27)Al magic-angle-spinning (MAS) NMR for the characterization of aluminum hydroxyphosphate adjuvants. Adjuvants were prepared by two different methods: batch-precipitation and precipitation at constant pH, using a wide range of different conditions. The adjuvant compositions showed no evident stoichiometric restrictions and varied as a function of the precipitation conditions. All the aluminum hydroxyphosphate adjuvants were found by (27)Al MAS NMR to contain both tetrahedrally and octahedrally coordinated aluminum. The octahedral form was always predominant. The chemical shifts corresponding to octahedral aluminum were at values intermediate between that of aluminum hydroxide (9 ppm) and those of phosphate-containing aluminum minerals such as variscite (-9 ppm) and varied with the phosphate content of the adjuvant. This was true even for adjuvants precipitated above pH 6 indicating that the phosphate is incorporated into the bulk solid phase contrary to predictions in the literature. Aside from the presence of tetrahedral and octahedral aluminum, there was no evidence in any of the adjuvants of distinct, structurally defined phases indicating that the adjuvants are not mixtures of distinct phases which differ significantly in the number of phosphorus atoms in the next-nearest-neighbor (NNN) position to aluminum.     

Malignant recurrence of childhood cerebellar astrocytoma: case report

A 15-year-old boy developed a glioblastoma in a cerebellar hemisphere 7 years after surgical excision and local irradiation of a pilocytic astrocytoma in the cerebellar vermis. Clinical and histopathological details are presented, and the literature on late malignant recurrence of childhood cerebellar astrocytoma is reviewed.     

Immunological function in head-injured patients. Relationship with severity of injury and age

The immunological function of 29 head-injured patients was investigated, with special reference to the relationships between changes in immunity and both severity of head injury and age. The patients were classified according to Glasgow Coma Scale scores (15, 9 to 14, and 3 to 8) and age (under 35, 35 to 65, and over 65 years). T cell subsets (OKT4 and OKT8) and Leu-11a cells were studied by flow cytometry with the use of monoclonal antibody. Lymphocyte stimulation indices were also evaluated. The percentage of OKT4 cells was significantly decreased in the young patients with severe head injury, whereas the percentage of OKT8 cells remained almost within the normal range. Thus, the ratio of OKT4 to OKT8 cells was decreased. The percentage of Leu-11a cells showed no correlation with severity of injury or age. Lymphocyte stimulation indices were reduced in cases of severe head injury. In this study, patients with severe head injury were immunosuppressed, particularly those under age 35.     

Inhibitory effect of disodium cromproxate on superoxide anion (O2-) generation and membrane potential changes in stimulated neutrophils

Disodium cromproxate is an antiallergic agent. This drug (0.5-2 mmol/L) inhibited O2- production by neutrophils induced by FMLP and PMA. However, the inhibition of FMLP-induced O2- generation was more pronounced than that induced by PMA. Disodium cromproxate also counteracted the changes in membrane potential in neutrophils induced by either FMLP or PMA. The actions of disodium cromproxate differed from those of propranolol, as propranolol had no antagonistic action on membrane potential changes induced by FMLP and PMA.     

Pathology of brain parenchyna in meningeal carcinomatosis; Immunohistochemical study with astroprotein (GFAP) and tubulin

Effects of leptomeningeal tumor on the brain parenchyma was studied by the immunohistochemical method with astroprotein (GFAP) and tubulin in a rat model of meningeal carcinomatosis. Thickening of subpial glial lining (external glial layer) and hypertrophy of subpial astrocytes, detected by the antiserum to GFAP, was the early sign of parenchymal involvement. The glial lining was continuous as far as the tumor cells were confined to the subarachnoid space, however, penetration of tumor cells into subpial brain was associated with disruption of the glial lining. Speculative role of this lining in preventing the tumor cell to infiltrate into brain tissue was discussed. In contrast to the prominent immunohistochemical changes in astrocytes, neuronal tubulin immunoreactivity was not altered even in the late stage of the disease. The present study demonstrated that the leptomeningeal dissemination of tumor cells did cause pathologic change in brain parenchyma as was evidenced by the reactive change of astrocytes. However, the preserved immunoreaction for tubulin suggested that the nerve cell damage was not severe even at the advanced stage of the disease. address for offprints     

Induction of apoptosis by N-(4-hydroxyphenyl)retinamide in glioma cells.

N-(4-hydroxyphenyl)retinamide (fenretinide) is a synthetic retinoid with anticancer properties. We investigated the effects of fenretinide on the growth of glioma cells. Four glioma cell lines (C6, 9L, Med3 and U87) were treated with fenretinide. Cell viability and independent growth was determined by MTS assay and soft agar assay, respectively. The induction of apoptosis was evaluated by microscopic examination, flow cytometric DNA content analysis, and in situ TdT methods. Fenretinide markedly reduced cell viability of all the glioma cell lines examined at a range of concentrations from 1 to 10 microM. In all cell lines examined, fenretinide also induced morphological changes consistent with apoptosis, including cellular shrinkage, chromatin condensation, and nuclear fragmentation. Flow cytometric analysis also revealed an apoptotic pattern of the DNA content, and in situ detection of apoptosis showed increased incorporation of digoxigenin-nucleotide triphosphate in fenretinide-treated glioma cells. These findings indicate that fenretinide inhibits the growth of glioma cells via the induction of apoptosis, suggesting potential clinical use of fenretinide for treatment of glioma patients.     

Capillary permeability factor produced by C 6 glioma cells: role in peritumoral brain edema and possible mechanism of glucocorticoid action

We studied whether C6 glioma cells produce a diffusible factor that increases capillary permeability of rat brains. Culture supernatant after 4 hours' incubation of C6 glioma cells in serum-free medium was obtained (SUP-N). SUP-N was concentrated 80-fold by dialysis-concentration (MW cut off was 10 kd) (SUP-C). These two supernatant fractions were tested for capillary permeability activity by their infusion into normal rat brains (right caudate-putamen). Control materials (MEM or concentrated MEM) were also infused into the left caudate-putamen as well as supernatants. Capillary permeability was measured by a quantitative autoradiographic method with 14C-aminoisobutyric acid (AIB) and expressed as an unidirectional blood-to-brain transfer constant (K). Effects of infusates were quantitatively estimated by two parameters, i.e., the highest K value (Kmax) (microliter/g/min) and the spatial extent (D1/2) (mm). The protein concentration of SUP-N and SUP-C was 15 and 950 micrograms/ml, respectively. SUP-N showed a slight increase of capillary permeability, particularly, around the needle track (infusion site) in the brain, but it was not significantly different from the control on the value of Kmax. On the other hand, SUP-C markedly increased capillary permeability (Kmax; SUP-C: 10.83 +/- 0.99, control: 2.53 +/- 0.22, p less than .001) and the effect was much more extensive than that of SUP-N (D1/2; SUP-C: 2.23 +/- 0.26, SUP-N: 0.83 +/- 0.07). A factor in SUP-C increased capillary permeability after a lag phase of 1.5 hours reaching the maximum after 6 hours of infusion, and 24 hours later the effect declined to 30% of Kmax at 6 hours.(ABSTRACT TRUNCATED AT 250 WORDS)