Significant gene expression of insulin-like growth factor II and proliferating cell nuclear antigen in a rapidly growing recurrent pituitary acth-secreting adenoma.

BACKGROUND: We quantified the expression of various growth-related factors in an adrenocorticotropic hormone (ACTH)-secreting adenoma that had recurred very rapidly as invasive macroadenoma. METHODS/RESULTS: A 43-year-old woman underwent successful transsphenoidal surgery for Cushing's disease. Seven years later, she was admitted to our ward for further endocrine examinations. In spite of a very high plasma ACTH level, the serum cortisol level was normal. Discrepancies between ACTH and cortisol levels were detected on the basis of diurnal rhythms, dexamethasone suppression tests, and corticotropin-releasing hormone test. The patient showed no clinical features of Cushing's disease. Magnetic resonance imaging of the pituitary showed an almost empty sella, and no microadenoma was found. These results, along with those of Sephadex column gel filtration and high-performance liquid chromatography of plasma-immunoreactive ACTH, suggested that the patient's residual corticotrophs secreted biologically inactive ACTH. Two years later, the patient suddenly developed diplopia and right abducens nerve palsy. She was slightly moonfaced and centrally obese. Her plasma ACTH and serum and urinary free cortisol levels were elevated, although discrepancies between ACTH and cortisol still existed. Magnetic resonance imaging revealed a large pituitary mass with suprasellar and cavernous sinus extensions. The tumor was excised, and the proopiomelanocortin gene and the expression of growth-related factors were analyzed. No mutations were found in the ACTH-coding region of the proopiomelanocortin gene. A significant expression of insulin-like growth factor II and proliferating cell nuclear antigen mRNAs was demonstrated. A high MIB-1 antibody labeling index was also detected in the adenoma tissue, suggesting high Ki-67 expression. CONCLUSION: These growth- and proliferation-related factors might be involved in the rapid growth and aggressiveness of this patient's pituitary adenoma.

Cerebellopontine angle lymphoma: a case report and review of the literature.

BACKGROUND: Although malignant lymphomas of the central nervous system have been reported to be increasing in frequency, cerebellopontine (CP) angle lymphoma is rare and only 13 cases have been reported previously in the literature. CASE PRESENTATION: A 63-year-old woman had progressive dizziness and nausea for 2 months. Computed tomography scanning and magnetic resonance imaging (MRI) revealed a mass lesion in the left CP angle, that was compressing the lateral-dorsal aspect of the pons and the fourth ventricle. This tumor was avascular on angiography. The tumor was surgically removed through a left lateral suboccipital approach. It was considered to arise from the subarachnoid space of the CP angle cistern. For some reason, the histologic diagnosis was not definitively made, and therefore radiation therapy was not planned. The tumor recurred within 50 days after the tumor excision. Surgical excision of the recurrent tumor was performed again. The histologic diagnosis was B-cell type malignant lymphoma. Radiation therapy was performed. In the 27 months since irradiation, a recurrent tumor has not been detected on MRI. CONCLUSIONS: Although erosion and expansion of the internal auditory canal suggest an acoustic neurinoma, CP angle lymphoma can, in rare circumstances, erode the internal auditory canal. There are three distinct patterns in which malignant lymphomas occupy the CP angle: (1) an extra-axial CP angle lymphoma, (2) an intra-axial lymphoma extending to the CP angle, and (3) a leptomeningeal lymphoma presenting as a CP angle lesion. Although malignant lymphomas rarely occupy the CP angle, it should be considered in the differential diagnosis of CP angle tumors. It is desirable to obtain a frozen section in all CP angle tumors during surgery to identify the tumor, because aggressive removal is not necessary, but radiation therapy should additionally be performed for malignant lymphomas.

Primary yolk sac tumor in the spinal cord.

A case of a primary yolk sac tumor of the spinal cord is reported. The patient was a 17-month-old Japanese girl, who was found to have an intramedullary mass at the upper thoracic level. The preoperative diagnosis was primary glioma, but histological examination of the surgical specimen revealed a yolk sac tumor. As there were no other lesions, the spinal cord lesion was considered to be the primary tumor. Based on our previous experience, we treated this patient with low-dose irradiation followed by combination chemotherapy with cisplatin, vinblastine and bleomycin. However, the effectiveness of this therapy was poor in this particular case, and the patient died of pyelonephritis with uncontrollable imbalance of serum electrolytes.

Combination chemotherapy (cisplatin, vinblastin) and low-dose irradiation in the treatment of pineal parenchymal cell tumors.

Pineal parenchymal cell tumors (PPCTs) with or without metastasis into the lumbar region by way of the cerebrospinal fluid were treated successfully with combination chemotherapy using cisplatin, vinblastin, and bleomycin (PVB) or cisplatin and vinblastin (PV) and low-dose irradiation (25 approximately 30 Gy). Our series included a case of pineoblastoma, two cases of mixed pinocytoma/pineoblastoma, and a case of pineocytoma, compared to which the data held by the All Japan Brain Tumor Registry (AJBTR) included information on 47 cases pineocytoma and 20 of pineoblastoma. All our patients have survived, with scores of 90% or over on Karnofsky's performance scale, for 2-12 years of follow-up so far; however, the 5-year survival rates of the patients recorded by AJBTR were 83% for pineocytoma treated with radiation and 43% without radiation; and 42% for pineoblastoma treated with radiation and 50% without radiation. Incomplete or varied chemotherapeutic regimens used in different medical centers to treat PPCTs precluded an evaluation such as was made by AJBTR. Our results suggested that combination chemotherapy with low-dose back-up radiotherapy may be the treatment of choice for primary or recurrent disease with or without dissemination in PPCTs.

A case of Rathke's cleft cyst with apoplexy.

We report a case of Rathke's cleft cyst associated with cholesterin granuloma in an 8-year-old girl with apoplexy. She was admitted to our hospital in April 1996 because of repeated headache and deep ophthalmic pain, without any visual disturbance. Computed tomography (CT) of the pituitary demonstrated an intrasellar isodense mass extending to the suprasellar cistern. Magnetic resonance imaging (MRI) showed a high-intensity mass on both T1- and T2-weighted images. The preoperative diagnosis of this lesion was Rathke's cleft cyst associated with a craniopharyngioma and/or hemorrhage. Transsphenoidal microsurgery was performed, and a bloody coffee-like serous and mucinous-yellowish substance was evacuated. Curettage of the wall removed the yellowish hard mass and soft membranous tissue. Histological examination of this tumor revealed a Rathke's cleft cyst with cholesterin granuloma.

Induction of specific cytotoxic T lymphocytes against autologous brain tumor by crossreactive allo-tumor cell stimulation.

Cytotoxic T lymphocytes (CTL) against autologous malignant brain tumor were generated in peripheral blood lymphoid cells (PBL) prepared from a patient with a malignant brain tumor by stimulation of the cultured PBL for 7 days with attenuated crossreactive malignant melanoma (MM2) cells pretreated with mitomycin C. The crossreactive MM2 cells were effective for antigen stimulation for CTL induction in place of autologous glioblastoma cells, which are difficult to expand in culture. The optimal ratio between nylon wool-passed T lymphocytes and nylon wool-adherent accessory cells to induce CTL in the patient's PBL was found to be 25 to 1. In vitro-activated CTLs induced by MM2 were cytotoxic not only to MM2, but also to the autologous tumor cells in an HLA class I-restricted manner, and their surface phenotype was found to be CD3+ and CD8+. CTL therapy using cross-reactive allogeneic tumor cells as the stimulator could be clinically valuable to treat malignant brain tumors.

Survival probability, delayed mortality, and relationship between short-term outcome and long-term survival after aneurysmal subarachnoid hemorrhage.

The long-term survival probability, causes of delayed mortality, and relationship between short-term outcome and long-term survival after aneurysmal subarachnoid hemorrhage were retrospectively studied in 106 patients followed up for longer than 5 years. The Kaplan-Meier cumulative survival probabilities at 1 month, 6 months, and 5 years were 85.9%, 79.2%, and 66.8%, respectively. Six months after the onset, 41 patients made a good recovery (GR) and 34 were moderately disabled (MD). On the last follow-up day, 64 had good outcome (GR or MD) and eight had died. In contrast, there were nine patients with poor 6-month outcome (severe disability or vegetative state), seven of whom died within 5 years. Five of these seven patients had experienced intraventricular hemorrhage (IVH) on admission. A total of 15 patients died beyond 6 months, five died of complications related to shunts. Six-month outcome is a predictor of long-term survival and delayed mortality. Improved long-term survival requires the development of better management for IVH, improved 6-month outcome, and careful follow-up of patients who undergo shunting.

Fluorescence localization of anti-pregnant rat kidney antibody and lectin binding analysis in exencephalic rat embryos.

We sought to determine the distribution of anti-pregnant rat kidney serum (ARKS) in fetuses that subsequently developed a form of neural tube defect (NTD). We produced exencephaly in rat embryos by injecting a rabbit anti-pregnant rat kidney serum into the peritoneal cavity of pregnant Wistar rats on day 7 of gestation; 71.1% (27/38) of the rat embryos developed this anomaly. Fluorescence immunohistochemical studies were performed to localize ARKS binding in the embryos. We also investigated the binding of two lectins, concanavalin A (ConA) and wheat germ agglutinin (WGA), to glycoconjugates on neuroepithelium during the process of neurulation in rat embryos injected with normal rabbit serum (NRS) and ARKS. We found for the first time that ARKS directly affected the neural tube during neurulation. Intense fluorescence was observed on the luminal side of the neuroepithelium in the intercellular region and on the basement membrane of the neural tube in embryos on day 9 of gestation (GD9). In GD21 embryos there was much more intense fluorescence in the extracellular matrix and the ependymal lining cells of the ventricles than in controls. The binding of the two lectins on the cell surface of the neuroepithelium during neurulation was different in rat embryos injected with ARKS than in normal embryos injected with NRS. These results support the idea that simple nonclosure and overgrowth constitute the mechanism of NTD. However, the lectinbinding data suggest that dysraphic states may be induced by cell-to-cell adhesive molecular failure.

Supra- and infratentorial multiple cavernous angiomas in an infant: report with MR evaluation of an unusual case.

A rare case of multiple cavernous angiomas with repeated hemorrhages in a 9-month-old male infant is presented, together with sequential computed tomography (CT) and magnetic resonance (MR) images. The infant underwent hematoma evacuation for left cerebellar hemorrhage and his postoperative course was uneventful. The multiple cavernous angiomas receded gradually without any treatment except the hematoma evacuation. Two years following presentation, he continues to do well. To the authors' knowledge, this is the first report of multiple cavernous angiomas with brain stem involvement in an infant.

Role of cytokines, tyrosine kinase, and protein kinase C on production of superoxide and induction of scavenging enzymes in human leukocytes.

We investigated the effects of proximal modulators of cytokines, tyrosine kinase (TK), and protein kinase C (PKC) on reactive oxygen species (ROS) generation and the induction of scavenging enzymes, superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) of human neutrophils and lymphocytes, by using IL1-alpha, TNF-alpha, and IFN-gamma and neutralizing antibodies to these cytokines. Inhibitors of TK (ST638 and herbimycin) or PKC (H-7, calphostin, and staurosporine) were also used. The results revealed that both (O2)- generation stimulated by five different agents (opsonized zymosan, A23187, PAF, PMA, and fMLP) and the inductions of all three scavenging enzymes were potentiated by priming with TNF-alpha. In contrast, both (O2)- generation and enzyme induction were attenuated by priming with IL1-alpha, with the exception of PMA-stimulated (O2)- generation. IFN-gamma decreased (O2)- generation but increased scavenging enzyme induction. Antibodies to all three cytokines and all the TK and PKC inhibitors decreased (O2)- stimulated by most agents, but markedly enhanced (O2)- levels stimulated by PAF. Induction of all three enzymes was enhanced equally by low concentrations of each of the three anticytokine antibodies, while each of the TK or PKC inhibitors decreased induction of SOD and GSH-Px and increased catalase induction. These results suggest that both ROS generation and scavenging enzyme induction are controlled in complex ways by the actions of these three proximal mediators. This supports our hypothesis that disturbances in the regulation of early events of cell activation can lead to oxidative tissue injury.

Immunohistochemical study of medulloblastoma with a monoclonal antibody against human copper and zinc-superoxide dismutase.

Superoxide dismutase (SOD) expression in tumor tissues was investigated in 10 cases of medulloblastoma by immunohistochemistry, using a monoclonal antibody against human copper and zinc-superoxide dismutase. Abundant SOD was expressed in tumors from patients with poor outcomes and little SOD in patients with good outcomes. These results suggest that resistance to adjuvant therapy depends on the amount of SOD in tumor tissues. The effects of adjuvant therapies for medulloblastomas depend on the production of free oxygen radicals, so if tumor cells contain a free radical scavenger such as SOD, the effects of adjuvant therapy may be reduced. Measurement of SOD in tumor tissues may be useful as a prognostic indicator for medulloblastoma.

[The correlation of immunohistochemical expression of human manganase-superoxide dismutase and outcome of the patients with medulloblastomas].

There in no clear indicator for making a prognosis in patients with medulloblastoma. The effects of adjuvant therapy on the tumor are exerted through free radicals that emerge in the cytoplasm of tumor cells following chemotherapy and/or radiotherapy. Thus, free radical scavengers, such as superoxide dismutase (SOD), in tumor cells may antagonize the effects of adjuvant therapy. In order to determine whether there is a correlation between SOD levels and the prognosis of medulloblastoma patients, SOD expression in tumor tissue was investigated immunohistochemically in eleven cases of medulloblastoma by using a polyclonal antibody against human manganase SOD. Abundant SOD was expressed in the tumors of patients with poor outcomes whereas there was little SOD expression in patients with good outcomes. This suggests that resistance to adjuvant therapy depends on the level of SOD in tumor tissue. The effect of adjuvant therapy on medulloblastoma depends on the production of oxygen free radicals. Thus, if the tumor cells contain free radical scavengers, such a SOD, the effects of adjuvant therapy may be reduced. Measurement of SOD in tumor tissue is useful as a prognostic indicator in medulloblastoma.

The distribution fields of sensory neurons in the human thalamus.

Thalamic neurons were identified by activity related to passive joint movement, active joint movement, tapping stimulation, and light touch stimulation during surgery to treat movement disorders. The neurons were classified into three types: movement-related neurons, tapping-related neurons, or superficial sensory neurons. Tapping-related neurons had characteristics of lemniscal sensory neurons and occupied the border area of movement-related neurons and superficial sensory neurons. Tapping-related neurons showed a laminar distribution 1.0-1.5 mm in width in the anterodorsal region of the nucleus ventrocaudalis. Results suggest that the distribution pattern of tapping-related neurons in the human thalamus is consistent with the functional distribution pattern found in the monkey thalamus.

Classification of hydrocephalus and outcome of treatment.

PURPOSE: Retrospective analysis in cooperative study of hydrocephalus at institutions of members of the Research Committee on Intractable Hydrocephalus sponsored by the Ministry of Health and Welfare of Japan was performed to determine the functional prognosis for all types of hydrocephalus and thus to clarify the outcome. METHODS: In preparation of this study, we have proposed the definition, clinical classification and diagnostic criteria of hydrocephalus. We have classified non-tumoral hydrocephalus into eight types based on its etiology and the time of onset. To establish the diagnosis in each type of hydrocephalus, we have set up inclusion and exclusion criteria, as well as supplementary criteria which are useful for its diagnosis. RESULTS: Analysis of the 1450 cases of hydrocephalus of various etiologies stored in the data base obtained from the study for each type of hydrocephalus revealed that following types and conditions were associated with a neurologic deficit: (1) early fetal hydrocephalus, (2) overt neonatal hydrocephalus, (3) hydrocephalus associated with such severe brain malformations as hydranencephaly, holoprosencephaly and lissencephaly, (4) hydrocephalus associated with severe brain damage, (5) hydrocephalus associated with epilepsy, (6) hydrocephalus shunted late after detection, and (7) hydrocephalus complicated by a shunting operation. CONCLUSION: The postnatal functional outcome was significantly poor in fetal hydrocephalus diagnosed in the early gestation. Childhood onset hydrocephalus showed a poorer outcome than adult hydrocephalus.

[A case of myogenic intractable pain due to thalamic hemorrhage relieved by Vim-Vo thalamotomy].

A 58-year-old female patient with myogenic intractable pain due to thalamic hemorrhage which was relieved by stereotactic Vim-Vo thalamotomy was reported. She had an intractable pain, involuntary movement and deep sensory disturbance in her right arm. We performed stereotactic Vim-Vo thalamotomy using electrophysiological technique to relieve her involuntary movement and myogenic intractable pain. The electrophysiological recordings suggested the followings: (1) The destructive lesion by thalamic hemorrhage was located on from posterior border of Vim nucleus to the upper half of Vc nucleus. (2) Most of Vim neurons remained as intact state. (3) Thalamic electrical activities were relatively enhanced in the Vim nucleus. From these data, we can deduce that the deep sensory inputs reach the border area of Vim nucleus and Vc nucleus in the human thalamus. IMP-SPECT scans were performed before and after the operation. IMP-SPECT scan before operation showed us the contra-lateral cerebellar low perfusional state (crossed cerebellar diaschisis). This crossed cerebellar diaschisis disappeared after the operation. This result suggested that the interaction of cerebellum and Vim nucleus was very close. The above mentioned speculation was more compatible to Jones & Hirai's new parcellation of the human thalamus than to Hassler's.

Scalp hair loss caused by octreotide in a patient with acromegaly: a case report.

We used octreotide to treat a woman with acromegaly and observed pituitary adenoma shrinkage after 5 months. Diffuse scalp hair loss occurred after 5 months, resulting in the discontinuation of treatment. After the cessation of octreotide, the hair loss stopped and hair growth resumed. Since bromocriptine did not effectively decrease the GH level of the patient, we decided to perform transsphenoidal surgery. After resection of the pituitary adenoma, her GH and IGF-1 levels were normalized. Although octreotide-induced scalp hair loss has not been well recognized, we should pay more attention to this side effect.

[Immunohistochemical study on the expression of copper and zinc-superoxide dismutase (Cu, Zn-SOD) in human adenohypophysis and pituitary adenomas].

A location of copper and zinc- superoxide dismutase (Cu, Zn-SOD) in adenohypophysis and pituitary adenomas was examined with immunohistochemical technique. Pituitary adenomas include thirteen functioning, five nonfunctioning; functioning adenomas consist seven prolactinomas, four growth hormone (GH) secreting, two adrenocorticotropic hormone (ACTH) secreting adenomas. Three specimens of normal adenohypophysis were used for control study. The Cu, Zn-SOD was localized diffusely in the cytoplasm of normal adenohypophyseal cells and the tumor cells. Sometimes immunoreactive products of Cu, Zn-SOD revealed in the cytoplasm of endothelial cell, neutrophil, macrophage and the cell membrane of erythrocyte in the vessels. The content of Cu, Zn-SOD in normal adenohypophyseal cells and pituitary adenomas was markedly higher in normal cells than adenoma cells. No significant difference of the SOD content was observed not only in non-functioning adenoma but also in functioning adenoma cells including PRL, GH and ACTH cells.

Venous malformation in the posterior fossa: guidelines for treatment.

Venous malformations in the posterior fossa are relatively rare. Although the introduction of CT and MRI has made them easier to detect, their treatment is still controversial. Based on our experience with six patients and a review of the literature, we have tried to establish guidelines for their treatment. Since they have a benign natural course and may provide venous drainage in the posterior fossa, venous malformation found incidentally, unruptured venous malformation with nonhaemorrhagic complications, and those accompanied by small intracerebellar haematoma of less than 2 cm in diameter due to their rupture, should be treated conservatively unless they are associated with a coexistent malformation. Venous malformation with intracerebellar haematoma larger than 3 cm or reexpansion of the haematoma due to rebleeding should be treated surgically by evacuation of the haematoma. Resection of venous malformations in the posterior fossa should be restricted to cases in which the malformation is small and does not serve as a functional venous drainage route. Radiation therapy, including the "gamma-knife", may be a treatment of choice in the future.

[Two cases of craniopharyngioma associated with Rathke's cleft cyst].

Two rare cases of craniopharyngioma associated with Rathke's cleft cyst are reported. The patients were 74-year-old female and 12-year-old boy. The former complained bilateral impaired visual acuity and visual field disturbance with hypoprolactinemia, the latter complained diabetes insipidus and growth retardation. MR images of these cases demonstrated sellar resion tumors, which were composed with both cystic and solid component. Transsphenoidal tumor removal were performed to both cases, and their tumor tissues were studied by light and electron microscopy. The cyst wall were composed of three kinds of epithelial cells such as ciliated columnar cells, mucous cells and basal cells. The solid components were composed of stratified squamous cells. These two components shifted each other. For these facts, to consider that both Rathke's cleft cyst and craniopharyngioma originate in remnants of Rathke's pouch, it is concluded that Rathke's cleft cyst cells sometimes cause differentiation to craniopharyngioma on its growth process.