Drug resistance and apoptosis in ENU-induced rat brain tumors treated with anti-cancer drugs.

To cast light on the mechanisms of drug-resistance, experimental brain tumors were immunohistochemically evaluated for expression of glutathione S-transferase (GST)-alpha, mu, pi, p-glycoprotein and apoptosis-related factors, such as bcl-2 and p53, as well as by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) method. Rat brain tumors induced by means of prenatal exposure to ethylnitrosourea (ENU) were treated with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and/or vincristine. Tumors more than 2 mm in size were considered to be drug resistant. The expression of GST-mu was strongly positive in ACNU-treated brain tumors, while p-glycoprotein was overexpressed in vincristine-treated brain tumors. Neither p53 nor bcl-2 expression directly correlated with apoptosis identified by TUNEL method, but tumors lacking apoptotic cells always demonstrated the expression of either GST-mu or p-glycoprotein. These results indicate that tumors resistant to chemotherapy might not be susceptible to induction of apoptosis, and therefore that mechanisms of drug resistance are related to programmed cell death in brain tumors.

Expansive laminoplasty for multilevel cervical OPLL.

Expansive laminoplasty is a new technique for the management of cervical ossification of the posterior longitudinal ligament (OPLL). Twenty patients were followed up for an average 3-year period. Follow-up examinations were performed every 3 months and at 1-year intervals. On lateral radiographs, the average increase in the anteroposterior (AP) diameter of the canal was 42%. Bone fusion was documented on computed tomography (CT) studies 3 months after surgery in 96% of patients. An average 83% of normal range of motion was preserved on long-term follow-up (3 years on average). Postoperative improvement over the same interval increased from an average preoperative Japanese Orthopaedic Association score of 7.9 to 14.1 Expansive laminoplasty as described is safe and has a high fusion rate, while better preserving the normal range of motion.

Microvascular changes associated with postischaemic hypoperfusion in rats.

The present study was undertaken to explore the cause of postischaemic hypoperfusion through morphological observations of the microstructure of brain cortex capillaries in rats with postischaemic hypoperfusion. Sixteen rats were used. The left middle cerebral artery of each animal was occluded for one hour (n = 8) or 2 hours (n = 8) and was followed by reperfusion for 2 hours. The regional cerebral blood flow (rCBF) of the ischaemia induced brain cortex was monitored continuously during the experiment and the microstructure of the brain cortex capillaries was then observed under electron microscope. Postischaemic hypoperfusion was observed in both ischaemia groups. The rCBF after (1.5 hours of reperfusion was significantly lower in the 2-hour ischaemia group than in the one-hour ischaemia group. The number of endothelial microvilli (MV) per capillary in the one-hour ischaemia group did not differ significantly from the control (the right cortex capillaries), whereas it was significantly higher in the 2-hour ischaemia group (p < 0.05). The ratio of the inner diameter to the outer diameter of capillaries decreased significantly in both ischaemia groups, and the ratio in the 2-hour ischaemia group was significantly lower than that in the one-hour ischaemia group (p < 0.05). Thus the present study statistically revealed that as postischaemic perfusion of the brains decreases, the number of MV increases, and endothelial cells swell more markedly. These microvascular changes seem to represent morphological factors associated with postischaemic hypoperfusion.

Immunohistochemical study of glutathione S-transferase-pi in meningiomas.

Immunostaining for glutathione S-transferase-pi was investigated in various subtypes of meningioma for the purpose of biological characterization. Specimens included five normal meninges and 25 meningiomas (10 meningothelial type, 6 fibrous type, 5 transitional type, 3 microcystic type, and 1 secretory type). In the meningothelial type, most cells showed strongly positive staining. In the fibrous type, all cells were negative. In the transitional type, only the meningothelial components were positive. In the microcystic type, meningothelial cell clusters and arachnoid trabecular cells were positive. In the secretory type, the meningothelial components and the pseudopsammoma-body-producing cells were positive. These results suggest that the meningothelial type and the fibrous type have a different basis of development and biological features. The results also suggest that arachnoid trabecular cells and meningothelial cells share the same origin, and that the arachnoid trabecular cells serve as supportive cells and as cells which detoxify harmful substances in the subarachnoid space. The pseudopsammoma-body-producing cells in the secretory type represent the outcome of epithelial differentiation of meningothelial cells with their biological character being preserved.

Clinicopathological study on pineocytoma.

Six cases of pineocytoma, which had developed in the parenchyma of the adult pineal body, were examined immunohistochemically and under an electron microscope, after the malignancy of each case had been determined using our classification. One case was rated as grade 1 showing a lobular structure and resembling the normal pineal body. Two cases were rated as grade 2 without a lobular structure but with pineocytomatous rosettes (P-rosettes). Two cases were rated as grade 3 without P-rosettes but with few mitotic figures. One case was rated as grade 4 with marked cellular pleomorphism, numerous mitotic figures and necrotic foci. When examined immunohistochemically, neuron-specific enolase was positive but glial fibrillary acidic protein was negative in all cases. Under an electron microscope, all cases showed abortive synapses, and clear or dense core vesicles. These findings allow us to make two conclusions. First, pineocytoma is always a tumor of neuronal lineage, regardless of their grade of malignancy. Second, the grade 4 pineocytoma should be distinguished from the type of tumor classically called "pineoblastoma." That is, the former seems to be a biologically dedifferentiated tumor, while the latter seems to be biologically undifferentiated tumor.

Approach through the temporal horn of the lateral ventricle for clipping of large dorsal type basilar bifurcation aneurysms.

The authors describe an approach through the temporal horn of the lateral ventricle which proved to be useful for clipping of a large dorsal type basilar bifurcation aneurysms. It facilitates the preservation of the perforating arteries behind the aneurysm, because it gives sufficient working space to move the aneurysm dome. Furthermore this approach avoids many of the disadvantages of other approaches, especially the risk of iatrogenic injuries of the Sylvian or Labe's vein.

Pleomorphic adenoma of the lacrimal gland manifesting as exophthalmos in adolescence--case report.

A 16-year-old girl presented with a pleomorphic adenoma of the lacrimal gland manifesting as left painless exophthalmos which had persisted for 3 years. Computed tomography revealed a tumor about 15 mm in diameter in the superolateral site of the left orbit. The tumor was removed completely by combined orbitofrontal craniotomy through a transcranial approach. Histological examination demonstrated the growth of tumor cells as glandular cavities or sheets, with myxoid and partly chondroid connective tissue stroma. Pleomorphic adenoma of the lacrimal gland is unusual in adolescents.

[Ultrastructural morphological changes of cortical microvessels following transient cerebral ischemia--a transmission electron microscopic study].

Post-ischemic hypoperfusion may play a significant role in reperfusion injury. Since there is no established treatment for hypoperfusion, however we decided to explore the morphological cause of post-ischemic hypoperfusion. In this study we used transmission electron microscopy to investigate the capillaries in ischemic/reperfused neocortex induced by 2 hours of middle cerebral artery occlusion followed by either 3 or 24 hours of reperfusion in 14 cats. Post-ischemic hypoperfusion was confirmed by measuring regional blood flow through a cranial window just above the left ectosylvian gyrus, which has poor anastomosis. A greater number of endothelial microvilli and capillary endothelial cell swelling were detected in the ischemic/reperfused neocortex, when compared with contralateral control neocortex. Especially after 24-hour reperfusion, collapse of some capillaries was observed with severe perivascular glial swelling and adhesion of PMN leukocytes to the endothelium. These findings yielded the following statistically significant results. 1) The number of endothelial microvilli in the ischemic/reperfused neocortex (mean +/- SD/1 blood vessel = 6.58 +/- 4.32) was significantly greater than in the control neocortex (3.13 +/- 2.68, p = 0.0001). 2) The ratio of capillary inner diameter (ID) to outer diameter (OD) in the ischemic/reperfused neocortex (ID/OD%, mean +/- SD = 75.4 +/- 16.7) was significantly smaller than in the control neocortex (89.2 +/- 10.8, p = 0.0001), indicating endothelial cell swelling. We concluded that these ultrastructural changes might be the cause of the multifactorial development of post-ischemic hypoperfusion, and that especially the number of endothelial microvilli and the endothelial cell swelling ratio might serve as morphological indicators of therapeutic efficacy for reperfusion injury in experimental studies.

Medulloblastoma associated with cysts and calcifications--case report.

An 11-year-old boy presented with medulloblastoma occurring in the cerebellar vermis. Computed tomography and magnetic resonance imaging revealed numerous cysts and calcifications in the tumor. The tumor was subtotally removed and cellular synchronization radiation therapy given. He was discharged without neurological deficits. Histological examination showed the cysts represented necrotic foci. Macrophages, which appeared around the necrotic foci, were important in the development of the calcifications via proliferation of collagen fibers.

Inhibitory effect of potassium citrate on rat renal tumors induced by N-ethyl-N-hydroxyethylnitrosamine followed by potassium dibasic phosphate.

Potassium dibasic phosphate (PDP) was administered at a concentration of 10% by weight in basal diet to unilaterally nephrectomized Wistar rats previously given 1000 ppm N-ethyl-N-hydroxyethyl-nitrosamine (EHEN) in the diet for 2 weeks. To study the effect of alkalinization on renal mineralization, some animals concomitantly received 5% potassium citrate (PC). Feeding PDP alone promoted adenomatous hyperplasias, which were regarded as preneoplastic lesions, as well as renal cell tumors in EHEN-initiated rats, whereas the addition of PC to PDP diets reduced the promoting effect. Histopathology, serum biochemistry and urinalysis indicated retardation of renal calcium crystallization by PC. Two other phosphate salts, sodium phosphate (SP) and calcium phosphate (CP), were also administered. SP showed a slight promoting effect on adenomatous hyperplasias and a 2-fold increase in the yield of renal cell tumors, while CP induced a clear reduction of both lesions, over EHEN alone. The promoting effects of both PDP and SP and the inhibitory effect of PC were somewhat correlated to 5-bromo-2'-deoxyuridine labeling indices, the degree of nephropathy, and mineralization in the kidney. Immunohistochemically, the nephropathy induced by phosphate salts was not linked to alpha 2u-globulin. A pathogenesis for renal carcinogenesis is suggested in which nephropathy associated with mineralization enhances the development of renal cell tumors.

Cortical and subcortical cavernous angioma: a comparison of patients with and without hemorrhage as the initial symptom.

Cavernous angioma is a benign vascular hamartoma with an obscure etiology. Clinical, radiological, and histological features of 24 cases of cortical and subcortical cavernous angiomas were analyzed to investigate the etiology. The lesions were classified as hemorrhaging (8 cases) or non-hemorrhaging (16 cases) according to the initial symptom. Age, sex, location, calcification and postcontrast enhancement by computed tomography (CT), tumor staining by angiography, and calcification and hemosiderin by histological examination were analyzed. Multivariate analysis showed that calcification by CT and histological examination correlated with non-hemorrhaging cases. Histological examination showed that calcification occurred inside and outside the blood vessels, within the vessel walls and in the adjacent brain tissue. Hemosiderin was also seen in most cases. These findings suggest that cavernous angiomas without hemorrhage have a poor circulation, resulting in minor recurrent bleeding and thrombosis, as well as calcification.

Effect of methyl mercury on prostaglandin synthesis in rabbit kidney medulla slices.

Effects of methylmercuric chloride (MMC) in the absence and presence of ascorbic acid on the synthesis of prostaglandins E2 and F2 alpha, and the lipid peroxidation of rabbit kidney medulla slices were studied. MMC showed dose-dependent inhibition of prostaglandins E2 and F2 alpha formation. The lipid peroxidation was not stimulated by MMC alone. Ascorbic acid plus MMC were able to stimulate the lipid peroxidation markedly, but the lipid peroxidation induced by ascorbic acid plus MMC had no influence on prostaglandin E2 production decreased by MMC alone. These results suggest that MMC inhibits prostaglandin formation by affecting the activity of prostaglandin cyclooxygenase, but that lipid peroxidation is not directly responsible for this inhibitory effect of MMC.