Eiji Yoshino

Estrogen receptors in brain tumors.

We examined the cytosolic estrogen receptor (ER) level in tumor tissue from 77 patients: 36 meningiomas, 20 gliomas (12 glioblastomas, 2 cerebellar astrocytomas, 2 ependymomas, and 4 medulloblastomas), 8 neurinomas, 7 pituitary adenomas (2 prolactin-producing adenomas, 1 growth hormone-producing adenoma, and 4 nonfunctioning adenomas), and 6 metastatic brain tumors (1 from breast cancer, 4 from lung cancers, and 1 from colon cancer). Nuclear ER levels were assayed in 11 meningiomas and 2 glioblastomas. ER was determined by the dextran-coated charcoal method and calculated by Scatchard analysis, Cytosolic ER was detected in 100% of the pituitary adenomas, 50% of the meningiomas, 50% of the metastatic brain tumors, 25% of the neurinomas, and 15% of the gliomas. In gliomas, only medulloblastomas had ER activity. Nuclear ER was found in three premenopausal women with meningioma. The dissociation constant of the ER complex was, in each case, less than 10−9M. These observations suggest that some brain tumors may be responsive to estrogen via the cellular ER.

Multivariate analysis of factors affecting postoperative survival in malignant astrocytoma

SummaryFifty-eight patients with supratentorial malignant astrocytoma were analyzed statistically to evaluate the actors most important for predicting postoperative survival. Clinical information such as age, sex, duration of preoperative symptom, Karnofsky score at admission and at discharge, location of tumor, amount of tumor removal, number of operations, and postoperative survival in months, together with data on radiation and chemotherapy were analyzed by chi square test, t-test, and multivariate analysis. Cytofluorometric DNA quantification using paraffin embedded specimens was also performed in 20 cases and these data were also evaluated.Multiple correlation coefficient, and therefore the total statistical accuracy, increased to 0.824 when data of DNA quantification, percentages of S phase cells and of polyploid cells, were included. Multivariate analysis revealed that 6 items were the major factors for predicting postoperative survival, i.e. the location of tumor, the Karnofsky score at discharge, the percentage of S phase cells, the number of operations, the percentage of polyploid cells, and the amount of tumor removed. Based on this analysis, the estimated survival time could be expressed as a formula.

Chronological Positron Emission Tomographic Study of Severe Diffuse Brain Injury in the Chronic Stage

Cerebral blood flow and metabolism were investigated in five patients with severe diffuse brain injury in the chronic stage, using positron emission tomography (PET). Regional cerebral blood flow, regional oxygen extraction fraction, regional cerebral blood volume, regional cerebral metabolic rate for oxygen, and regional cerebral metabolic rate for glucose were measured bilaterally in the frontal, temporal, occipital, and parietal gray matter, as well as the white matter of the centrum semiovale. In 4 of 5 patients, a follow-up PET study was also performed. In three cases, below-normal regional cerebral blood flow and regional cerebral metabolic rate for oxygen values accompanied by above-normal regional oxygen extraction fraction values, as well as low metabolism, were demonstrated in the initial PET studies. In two of three cases, clinical improvements were observed, and follow-up PET data also improved. These findings suggest that chronological PET studies may be able to assess quantitatively clinical improvements in patients with diffuse brain injury.

Rapidly growing aneurysm

A rare case of rapidly growing intracranial aneurysm is reported. The enlarged aneurysmal wall was extirpated and studied histologically. The cause of the rapid growth of the aneurysm is discussed.

Basic fibroblast growth factor messenger RNA is expressed strongly at the acute stage of cerebral contusion

Basic fibroblast growth factor (bFGF) has a neurotrophic effect both in vitro and in vivo, and is considered to play an important role in the maintenance of neuronal functions in the normal brain. Neural damage in brain contusion progresses after the primary injury of trauma because of cerebral hemodynamic and metabolic impairment including intracranial hemorrhage and/or brain swelling. Northern blot analysis of bFGF mRNA was performed in rats after cerebral contusion produced by our modified fluid percussion device. Expression of bFGF mRNA increased significantly on the second day after trauma. A possible role of bFGF is functioning to protect the critical neurons from secondary neural damage in cerebral contusion.

Value of high-resolution computed tomography in diagnosis of petrous bone fracture

High-resolution computed tomography (CT) was performed on 31 patients clinically suspected of having petrous bone fracture. The location of the fracture was demonstrated accurately in 28 patients (90.3%), whereas it could be diagnosed by plain skull film in only 17 patients (54.8%). The anatomic location of fractures demonstrated by high-resolution CT clearly corresponded to the clinical symptoms and signs. We have classified petrous bone fracture into five types according to the anatomic levels demonstrated on CT images. The findings indicate that high-resolution CT is extremely useful for diagnosing petrous bone fracture.

Studies on estrogen induced pituitary tumor in the rat with special reference to the relationship of the tuberoinfundibular dopamine neuron system

Pituitary tumors were experimentally induced in female Wistar rats by repeated injections of estradiol dipropionate. The hypothalamus and pituitary tumors were studied simultaneously by fluorescence histochemistry and immunohistochemistry. The pituitary gland became larger with a concomitant increase of serum prolactin in proportion to the dose of estrogen. Estrogen-induced pituitary tumor exhibited a proliferating prolactin cells by the peroxidase immunohistochemical method. Ultramicroscopical findings showed that these tumor cells were in an extremely hyperfunctional state.The dopamine neuronal perikarya in the hypothalamic arcuate nucleus and their terminals in the external layer of the median eminence were examined by fluorescence histochemistry in the rats bearing estrogen induced pituitary tumor and it was concluded that in our experimental conditions, estrogen effected directly on pituitary rather than on the hypothalamus and consequently dopamine synthesis in the arcuate neurons and its release into portal capillaries were accerelated simultaneously in order to inhibit prolactin secretion from tumor cells.

Extravasation of contrast medium during both computed tomography and cerebral angiography.

Extravasation of contrast medium demonstrated during computed tomography in a case of intracerbral hematoma is reported. The extravasation was also noted during cerebral angiography performed just after the computed tomography scan.

Positron Emission Tomography and Boron Neutron Capture Therapy System to the Patient with Malignant Brain Tumor

We have conjugated a positron tracer F-18 to [10B]boronophenylalanine (10B-BPA) to synthesize [18F]fluoroboronophenylalanine (18F-10B-DL-BPA or 18F-10B-L-BPA), and analyzed 1013-BPA metabolism on 27 cases of the various brain tumors by positron emission tomography (PET). These PET data revealed that 18F-10B-BPA using the DL-form was actively incorporated to the malignant tumor cells, showing high B-10 concentration and T/N ratio, which was suggested of the sufficient effectiveness of boron neutron capture therapy (BNCT) on the malignant brain tumor. The experimental studies were undertaken with rat glioma model which showed that BNCT using 10B-L-BPA brought the good antitumor effect on rat glioma and no side effect on normal brain. Under this PET-BNCT system, the patient with malignant brain tumor was treated.

A Basic Concept for PET-BNCT System

[10B]Boronophenylalanine (10B-BPA) has been used as a tumor selective boron carrier for boron neutron capture therapy (BNCT) in the treatment of malignant melanoma1. In the same way, it is thought to be a potential boron carrier for the treatment of malignant glioma2–4. Glioma infiltrates peripheral brain tissue and we always fall into the dilemma between resection and preservation of the infiltrated brain. Thus the treatment will be effective in these infiltrative tumors. In our studies of malignant glioma using positron emission tomography (PET), accumulation of 10B-BPA analog, [18F]fluoroboronophenylalanine (18F-10B-FBPA), in tumor lesion was dramatically revealed3. The metabolic analysis of this positron-emitting analog demonstrated that enhancement of the amino acid transport is a primary factor for the high accumulation3,5. [18F]Fluoroboronophenylalanine has been recognized as a compound that is incorporated into tumor cell selectively.