Immunohistochemical localization of apolipoprotein E in human glial neoplasms.

Immunocytochemical analyses revealed the presence and distribution of apolipoprotein E (apo E) in normal human brain tissue as well as in 77 human intracranial neoplasms. In normal brain tissues, the perikarya of astrocytes exhibited a strong positive reaction, whereas the Bergmann glia were stained to a moderate degree. However, no immunoreactivity was observed with neurons, oligodendrocytes, ependymal cells, and choroidal epithelium. Among the intracranial neoplasms, oligodendroglioma, choroid plexus papilloma, hemangioblastoma, primary malignant lymphoma, neurinoma, meningioma, pituitary adenoma, and craniopharyngioma were all negative. Immunoreactivity in the peripheral neuroblastoma was nil. However, the perikarya of astrocytomas and glioblastomas showed a positive reaction. Analyses on the degree of anaplasia and the amount of apo-E as an intensity of immunostaining showed a negative correlation. The astrocytic elements were stained in mixed oligoastrocytomas and medulloblastomas with glial differentiation. A few cases of ependymomas showed weak perikaryal immunostaining. Western blot analyses with anti-apo E antibody of a freshly prepared surgical specimen with astrocytomas revealed a single band with a molecular weight of approximately 37,000. The well differentiated cultured human astrocytoma cells secreted apo E into the medium. These lines of evidence suggest that apo E may serve as a potential marker specific for astrocytomas and glioblastomas, as well as an indicator of astrocytic tumor cell differentiation. The apo E localization in human brain tumors could be clinically relevant and diagnostically useful.

Structural organization of the mouse mitochondrial malate dehydrogenase gene.

Structural organization of the mouse mitochondrial malate dehydrogenase (EC 1.1.1.37) gene was determined by analyzing a genomic DNA fragment isolated from a cosmid library. The gene is 12,000 base-pairs long and contains nine exons interrupted by eight introns of various sizes. The 5' and 3'-flanking regions, and the exact sizes and boundaries of the exon blocks including the transcription-initiation sites were determined. In the 5'-flanking region, there is neither a TATA box nor a CAAT box. Instead of these sequences, there are six copies of the GGGCGG or CCGCCC sequence, which is a potential binding site for the transcription factor, Sp1. The 5'-flanking region up to about 600 nucleotides is G + C-rich (65%) and contains sequences compatible with the formation of a number of potentially stable stem-loop structures. S1 nuclease mapping and primer extension analysis demonstrated that transcription of the mitochondrial malate dehydrogenase gene initiates at multiple sites. Comparison of the nucleotide sequence of the promoter region of the mitochondrial malate dehydrogenase gene with that of the mitochondrial aspartate aminotransferase gene, revealed that there are several highly conserved regions between these two mitochondrial enzyme genes participating in the malate-aspartate shuttle.

Hemifacial spasm due to contralateral acoustic neuroma: case report.

A patient with a large acoustic neuroma had contralateral hemifacial spasm. On CT, the brainstem was markedly displaced and distorted by the tumor. After total removal of the tumor the hemifacial spasm was temporarily worse, but disappeared 14 days after the operation.

Morphological characterization of the rat striatal neurons expressing calcineurin immunoreactivity.

Calcineurin, a multifunctional Ca2+ (divalent cations)-dependent calmodulin-stimulated phosphoprotein phosphatase, has been reported to be present in the striatal neurons which project to the globus pallidus and the substantia nigra. In the present study, we examined what types of cells in the rat striatum express calcineurin. The calcineurin-positive neurons were of medium size (mean diameter of 16 microns) and constituted about 60-70% of the total neuronal population in the striatum. Under light microscopy, the calcineurin-positive neurons had round, triangular, or polygonal cell bodies with a relatively small amount of cytoplasm. Electron microscopic examination of 20 randomly selected striatal calcineurin-immunoreactive neurons revealed that their nuclei did not show any invaginations or intranuclear inclusions. The calcineurin-positive neurons were characterized by Golgi impregnation as the densely spinous type. On the other hand, it was demonstrated that calcineurin-positive neurons are a separate population from the diisopropylfluorophosphate-acetylcholinesterase-positive cells or nicotinamide adenine dinucleotide phosphate diaphorase-positive cells, by means of the combination of immunocytochemistry and enzyme histochemistry. In addition, simultaneous localization of calcineurin and substance P in a single cell was observed in some striatal neurons using a double immunostaining method. On the basis of these findings, it was considered that most calcineurin-immunoreactive neurons in the rat striatum may be classified as medium-size densely spiny neurons.

A pharmacokinetic simulation model for chemotherapy of brain tumor with an antitumor protein antibiotic, neocarzinostatin. Theoretical considerations behind a two-compartment model for continuous infusion via an internal carotid artery.

A pharmacokinetic two-compartment model for the treatment of brain tumors in man was simulated with the aid of a computer. The parameters necessary for the simulations such as inactivation rate constant, elimination rate constant, distribution volume, blood volume, cerebral blood flow, and cytotoxic drug concentration were either determined in this study or obtained from the literature. A proteinaceous antitumor antibiotic, neocarzinostatin (NCS), was utilized as a prototype drug because it has features making it advantageous in the treatment of brain tumor. In particular, NCS has an extremely short half-life in serum (t 1/2 less than or equal to 3 s), while it is relatively stable in the cerebrospinal fluid (CSF) (t 1/2 approximately 50 s). Therefore, the drug level in the cerebral compartment can be made adequately high with an appropriate infusion velocity into the cerebral compartment; however, it was possible to keep the plasma level of the drug much lower than the toxic level. Thus, few side-effects should result. In an in vitro study, NCS was found to exhibit its cytotoxicity to glioblastoma cells at a concentration as low as 0.005 microgram/ml. In contrast, the cytotoxicity was not apparent for the normal glia cells at 0.1 microgram/ml. The model being considered in this investigation is a two-compartment model, which consists of the cerebral compartment and the rest of the circulatory system of the body. In this case the drug is infused via an internal carotid artery. The results of pharmacokinetic simulation and dose regimens for NCs are presented, based on the effective concentration of the drug to glioblastoma cells in culture and the available pharmacological parameters.

The distribution of calcineurin in rat brain by light and electron microscopic immunohistochemistry and enzyme-immunoassay.

Calcineurin is the calcium (divalent cations)-dependent calmodulin-stimulated phosphoprotein phosphatase which is capable of dephosphorylating various substrate proteins. The subcellular and regional distribution of calcineurin in the rat brain has been studied by light and electron microscopic immunohistochemistry using antiserum against calcineurin. Immunoreactivity was observed in many neurons but was not detected in glial cells, such as astrocytes, oligodendrocytes and ependymal cells by the PAP method. Light microscopy demonstrates strong immunoreactivity in neuronal somata and neurites. By electron microscopy, calcineurin immunoreactivity was found to be present in dendrites including postsynaptic densities, somata, spines, axons and terminals. Calcineurin immunoreactivity was present in neurons throughout the brain, but a marked regional variation in strength of the immunoreactivity was observed. The caudatoputamen, hippocampal formation, and substantia nigra were strongly stained. Cerebral and cerebellar neocortex showed moderate immunoreactivity. In substantia nigra and globus pallidus, only neurites were stained, but neuronal somata not. The staining of the substantia nigra was thought to be due to that of the nerve terminals originating from the caudatoputamen, in view of the findings by cerebral hemitransection and electron microscopic immunohistochemistry. We developed an enzyme-immunoassay (EIA) for calcineurin. The sensitivity of the EIA was 1 ng (13 fmol) of calcineurin. We determined the level of calcineurin in various regions of the rat brain. The caudate nucleus, putamen and hippocampal formation showed a high concentration of calcineurin. The results are consistent with those obtained by immunohistochemistry.

Calcineurin as a neuronal marker of human brain tumors.

Calcineurin is one of the calmodulin binding proteins and a Ca2+-dependent and calmodulin-stimulated phosphoprotein phosphatase. We used antisera to the calcineurin as a cell-type-specific marker in order to identify neuronal cells in the rat brain and human neoplasms. In normal rat brain slices, basal ganglia were stained macroscopically, and other areas such as cerebral cortex, corpus callosum, cerebellar cortex, granular layer and pyramidal tract of the spinal cord were lightly identified as well. Under the light microscope, it was found that only the neuronal cells were stained, and astrocytes, oligodendrocytes, ependymal cells and vessels were not. Intracellular distribution of the staining showed various patterns and staining intensity of varying degree. Using the PAP method, localization of the calcineurin in formalin-fixed, paraffin-embedded tissues were studied in 65 human intracranial neoplasms, and in 11 human extracranial neoplasms. The neuronal elements of neuroblastoma, ganglioglioma, ganglioneuroma and retinoblastoma were clearly stained. In contrast, glioblastoma, astrocytoma, oligodendroglioma, ependymoma, meningioma, neurinoma, pituitary adenoma, craniopharyngioma, hemangioblastoma, hamartoma, lymphoma and mesenchymal tumor were all negative. Two cases out of 5 medulloblastomas were stained, but others were not. Although positive tumors disclosed various staining patterns and intensities, these results indicated that calcineurin could be a new neuronal marker in human brain tumors.

Evaluation of prototype equipment for digital subtraction angiography in diagnosing intracranial lesions.

Two prototype units for digital subtraction angiography have been developed by Japanese manufacturers. Their performance in demonstrating various intracranial lesions in 121 patients was evaluated. Comparison with conventional selective catheter angiography was possible in 77 patients. Digital subtraction angiography proved useful in preoperative evaluation of pituitary tumors when transsphenoidal surgery was being considered; demonstration of faint tumor stains which might be missed on conventional angiography; demonstration of larger aneurysms, arteriovenous malformations, and tumors as a screening technique; demonstration of abnormalities involving the dural sinuses; and follow-up of patients after surgery or embolization.

Syringomyelia and syringobulbia associated with an ependymoma of the cauda equina involving the conus medullaris: case report.

A patient with syringomyelia and syringobulbia secondary to an asymptomatic ependymoma of the cauda equina involving the conus medullaris is described. Delayed metrizamide computed tomography myelography was decisive for making the diagnosis of a highly extended syrinx associated with the tumor. Syringomyelic symptoms improved remarkably following the removal of the tumor, and the syrinx was not visualized in a postoperative study. The pathogenesis of syringomyelia associated with a caudally located spinal cord tumor is discussed.

Anterior basal encephalocele of the neonatal and infantile period.

Diagnosis of occult basal encephalocele is not difficult if the peculiar clinical and radiological signs of this anomaly are borne in mind. Recent surgery for transsphenoidal encephalocele has had better results than realized. However, high surgical risks may still be encountered in transsphenoidal encephalocele of the early infantile period, because the pituitary-hypothalamic structures are usually incorporated in the herniated encephalocele of this age group. Surgical indications for and operative approaches to transsphenoidal encephalocele in the infantile period are discussed on the basis of the authors' failure in transcranial repair, which resulted in early postoperative death due to hypothalamic dysfunction. Reviewing the reported cases of anterior basal encephalocele, a high correlation between transsphenoidal encephalocele, particularly in the pediatric age group, and allied malformations of the face, eye, and brain was disclosed. This characteristic malformation complex may be explained by a common pathogenetic mechanism operating in the embryonal period at about the stage of the anterior neuropore closure and occurring in the ventral surface of the cephalic end of the neural tube. Three cases of transsphenoidal encephalocele diagnosed in the neonatal period with progressive obstruction in the nasopharyngeal airway are also reported. A characteristic malformation complex consisting of median cleft face syndrome, optic nerve dysplasia, and agenesis of the corpus callosum was associated in two cases; the other patient had an extremely rare combination of septooptic dysplasia. Two patients died pre- and postoperatively, respectively; the other patient did not undergo operation because of grave multiple anomalies.

Intracranial extracerebral brain heterotopia. Case report.

The authors describe a case of intracranial heterotopic brain located on the medial one-third of the left sphenoid ridge, and enveloped in a huge cystic cavity. The heterotopic brain was resected successfully with satisfactory clinical results. The resected brain was 8 X 4 X 3 cm in diameter, of 7 or 8 months gestational age, and consisted of cerebrum, brain stem, and cerebellum. Anatomical and cytoarchitectural findings of the heterotopic brain are presented.

Prolactinoma of pituitary with associated amyloid-like substances. Case report.

A prolactin-secreting pituitary adenoma containing amyloid substance was studied by light and electron microscopy. The tumor was found in a 32-year-old woman who presented with a short history of amenorrhea and galactorrhea. Pituitary adenoma containing amyloid substance is a very rare entity, and the implications of this association are discussed. Previous reports, suggesting that mesenchymal cells or hormone-secreting tumor cells in pituitary adenomas produce amyloid substances, are reviewed.

Rhabdomyosarcoma of the brain.

The authors report a case of rhabdomyosarcoma originating in the fourth ventricle and review the eight comparable previous reports on true rhabdomyosarcoma, composed solely of mesenchymal elements. Tumors in most adults arose in the cerebral hemisphere, while those in children arose exclusively in the midline structures of the posterior fossa. The tumor in the author's case was initially benign and well circumscribed, but within 2 years had changed into a malignant rhabdomyosarcoma. The histological documentation during the interval is presented and discussed.

Microvascular decompression for hemifacial spasm. Patterns of vascular compression in unsuccessfully operated patients.

To determine the causative factors of unsuccessful microvascular decompression for hemifacial spasm, the follow-up results in 53 patients were assessed retrospectively. The mean follow-up period was 36 months. There were 32 patients who had compression of the seventh cranial nerve ventrocaudally by an anterior inferior cerebellar artery (AICA) or a posterior inferior cerebellar artery. Of these 32 patients, 30 (94%) had excellent postoperative results. Of 14 patients with more severe compression by the vertebral artery, nine (64%) had excellent results, three (21%) had good results, and two (14%) had poor results; in this group, three patients with excellent results experienced transient spasm recurrence. There were seven patients in whom the meatal branch of the AICA coursed between the seventh and eighth cranial nerves and compressed the dorsal aspect of the seventh nerve; this was usually associated with another artery compressing the ventral aspect of the nerve ("sandwich-type" compression). Of these seven patients, five (71%) had poor results including operative failure in one and recurrence of spasm in four. The authors conclude that the clinical outcome was closely related to the patterns of vascular compression.

Clinical and histopathological characteristics of gonadotropin-producing pituitary adenomas.

The clinical and histopathological characteristics in six cases of gonadotropin-producing adenoma are presented. Definitive diagnosis was made by the determination of gonadotropin levels in culture medium. Several authors have reported that gonadotropin-producing adenomas are very rare; however, hormonal assay of adenoma cell culture medium may indicate the real incidence of gonadotropin-producing adenomas to be greater than is thought. In reported cases, practically no endocrinological symptoms have been found suggesting increased gonadotropin levels, and basal values of plasma gonadotropins have been reported as only slightly over the normal range. Gonadotropin-producing adenomas may have been misdiagnosed as nonsecreting adenomas. The clinical characteristics of gonadotropin-producing adenomas can be summarized as follows: 1) a tendency for more rapid growth than nonsecreting adenomas; 2) prominent suprasellar extension with marked enhancement on computerized tomography; and 3) diminished response of luteinizing hormone (LH) alone in response to LH-releasing hormone (LH-RH) stimulation, and the ratio of peak follicle-stimulating hormone to peak LH in the LH-RH stimulation test is more frequently over 1:1 in cases of gonadotropin-producing adenoma than in cases of nonsecreting adenoma and craniopharyngioma. Immunoperoxidase staining revealed two kinds of adenoma cells, one intensely and the other faintly stained. Abundant mitochondria and few secretory granules were characteristic electron microscopic features. Oncocytic transformation of adenoma cells was suggested by immunoperoxidase staining and the electron microscopic appearance, and may suppress the elevation of circulating plasma gonadotropin levels. Thus, hormonal assay of adenoma cell culture medium and immunoperoxidase staining are essential for definitive diagnosis of gonadotropin-producing adenomas.

Classification of cervical spondylosis or disc protrusion by preoperative evoked spinal electrogram. Follow-up study.

The evoked spinal electrogram (SEG) was studied in 11 patients with cervical spondylotic myelopathy or disc protrusion. All the patients were severely handicapped before surgery. The evoked SEG was classified in three grades before and during surgery. Periodic follow-up studies were done at 18 to 35 months, with an average of 24 months. Four of six patients were normal or slightly abnormal SEG recordings showed satisfactory improvement of the disability; however, only one patient showed any improvement when the recording was moderately or severely abnormal. Location of the cord lesion and type of surgery were similar in all patients examined, and the difference was likely ascribed to the physiological change of the intramedullary structures. The evoked SEG provides some information relative to the surgical treatment of spondylotic myelopathy or disc protrusion with cord lesion.

Failure to detect papovavirus-associated T antigens in human brain tumor cells by anticomplement immunofluorescence.

To probe the possible presence of papovavirus-related T antigen(s) in human brain tumors, the imprinted or cultured cells at various passage levels were examined by anticomplement immunofluorescence using antisera to T antigen of each BK virus, JC virus, and simian virus 40. No T antigen was demonstrated in any tests with cells derived from 69 patients with various brain tumors. Twenty-two tumor cell strains cultured in the presence of a tumor promoter, phorbol ester, also failed to show the T antigen.

Migration of a dissected peritoneal shunt catheter into the scrotum.

Migration of a dissected peritoneal piece of the shunting material into the scrotum was encountered in a 1-year-old boy who had received a V-P shunt. Removal of the migrated shunt tube by inguinal exploration and herniorrhaphy were performed, and another V-P shunt was installed simultaneously. This case was considered worthy of reporting as a rare complication of a V-P shunt, and the causal mechanism is discussed with a review of the literature.

Cervical dermal sinus associated with meningitis and motor paralysis.

A patient is described with a congenital dermal sinus in the high cervical region who developed recurrent episodes of purulent meningitis associated with fluctuating paresis of the extremities. Subtotal excision of the dermal track in the cord resulted in good functional recovery.

Sinus pericranii with aneurysmal malformation of the internal cerebral vein.

A case of sinus pericranii is reported because of a previously unobserved clinical feature. There were associated anomalous dilated deep crebral veins and an aneurysmal venous malformation. Six years after the surgical occlusion of the sinus pericranii the aneurysmal malformation became thrombosed.