Phosphorylation of a proline-directed kinase motif is responsible for structural changes in myogenin.

Myogenin, a member of the MyoD family which governs skeletal muscle differentiation, was identified as a pair of phosphorylated bands on SDS-PAGE during myogenesis. The slow migrating form was found to be hyperphosphorylated myogenin. In vitro phosphorylation by CDC2 kinase caused a prominent reduction in electrophoretic mobility of myogenin. Furthermore, we demonstrated that phosphorylation of the serine residue at position 43 contributes to the modification of myogenin in vivo and in vitro resulting in the reduction in electrophoretic mobility. We propose here that a CDC2-like proline-directed kinase regulates myogenin activity through its phosphorylation.

A new method for measuring cerebrospinal fluid flow in shunts.

An implantable device for measurement of cerebrospinal fluid (CSF) flow in a ventriculoperitoneal shunt tube has been developed. The unit is energized by an extracorporeal high-frequency generator (200 KHz), and electrolysis creates bubbles in the shunt tube. Velocity of bubble flow is detected by a pair of ultrasonic Doppler probes placed a certain distance apart on the skin surface and in parallel with the implanted tube. The CSF flow rate is calculated taking into account velocity and tube diameter, and is expressed in ml/min. The unit consists of a coil with a capacitor, a silicon diode to rectify the high frequency, and a Zener diode to regulate maximum output voltage of 20 V. The output is fed to a pair of platinum electrodes placed inside the unit's tunnel through which the CSF flows. These components are molded in epoxy resin and coated with medical-grade silicone rubber. In animal experiments, CSF flow rates ranging from 0.033 to 1.0 ml/min could be measured by this flowmeter. Clinically, CSF flow has been measured to date in several cases. In two cases of communicating hydrocephalus occurring after the onset of cerebrovascular disease, and in which the CSF flow was continuously monitored for 24 hours, the flow rate ranged between 0.05 and 0.78 ml/min. The CSF flow rate fluctuates in a 24-hour period, increasing in the morning, especially between 12 midnight and 6 a.m., which suggests a circadian rhythm.

Statistical studies on evaluation of mild disturbance of consciousness. Study of a simpler scale for clinical use.

In an effort to express the grades of mild disturbance of consciousness (MDOC), or clouding of consciousness, 25 items were selected for application in clinical examination. Factor analysis of the 25 items revealed that MDOC has a two-factor structure; namely, the performance factor (F1) and the verbal factor (F2). This structure was maintained in the sequential examinations. Guttman's scale analysis showed that the scale using the 25 items may be considered to approximate a unidimensional scale. By item selection according to communality, the 25 items could be reduced to 12 items without losing the two-factor structure or the usefulness and reliability of the examination. The principal component analysis (PCA) score, the F1 score, and the F2 score, calculated from the 12 items, were found to be good scales to describe an overall picture and characteristics of the F1 and the F2 of MDOC, respectively. Furthermore, by means of the characteristic curve (ogive) method, it was revealed that MDOC consisted of four clusters of items, the F2 factor (mild), F1 factor (mild), F2 factor (moderate), and F1 factor (moderate), according to the MDOC severity, so that a simpler scale composed of a representative item from each cluster could be constructed which exhibited a high correlation coefficient with the original PCA score.

Referential derivation of epidural electroencephalogram in El mice.

Epidural EEG of 20 El mice is recorded under ketamine and xylazine anesthesia with epoxy coated silver balls as exploring electrodes. A stainless steel needle is placed subcutaneously near the nose as a reference electrode. Reproducibility of recording is remarkable. Multiple spike complex synchronizing on both frontal lobes is observed in 8 mice. Among them, small spikes preceding the multiple spike complex are also observed on the left frontal lead in 7 mice and on the right in 1 mouse. These spikes do not spread to occipital recordings. The discriminative ability of the recording is due to the coated electrode commonly employed with much larger animals and to suitable placement of the reference electrode. This simple and well known method permits the analysis of not yet satisfactorily explored the EEG of El mouse.

[Clinico-histological study of low-density non-enhancing glioma].

Some gliomas are not noticeably enhanced on initial computer tomography (CT) scans. Such low-density non-enhancing gliomas have a relatively long period between onset and surgery ranging from 5 to 25 months. The mechanism causing the low density over a certain period of time in the sequential CT findings was retrospectively investigated. Characteristic histological findings associated with such low-density areas were microcystic formation, necrosis, intratumoral edema, infiltrative growth, and absence of capillary proliferation. Proliferation of capillary vessels is characteristic of CT enhancement.

[Clinicopathological study on low grade glioma. In relation to malignant transformation].

The clinical status of patients with glioma is influenced by 1) the histological malignancy of the tumor, 2) the tumor volume, 3) secondary status such as brain edema or intracranial hypertension due to the tumor, and 4) the host immunity. Due to some improvement in at least 2) and 3) by the initial treatment, most low grade glioma cases pass through a clinically silent postsurgical period. However, at a certain point, transition to a high grade tumor malignant transformation may occur with exacerbation of the symptoms. Twenty-two cases of histologically established low grade glioma experienced over the past 7 years, in which immunological status was evaluated, were analyzed. Nine cases (41%) showed malignant transformation. Characteristic pictures of the clinical symptoms, computed tomography (CT) scan findings, immunological status, and morphological findings (mainly immunohistochemical examination) in nine cases were delineated. The findings at the time of exacerbation of the symptoms were as follows. In all cases CT scan demonstrated the change in the main lesion from low density to mixed density and were compatible with a high grade glioma. Reduction in host immunity was verified. Morphological increase in the tumor volume, increase in histological malignancy and deterioration in the secondary status due to the tumor were confirmed. Necrosis of the tumor cells as well as increase in giant cells and gemistocytes were observed. Immunohistochemical analysis revealed a decrease and irregularity in glial fibrillary acidic protein positive cells and positive processes as well as increase in vimentin intensity. These findings demonstrate change in the biological characteristics of the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

[Brain metastasis from primary pericardial mesothelioma. Case report].

A 50-year-old female was admitted because of nausea, vomiting, and cerebellar ataxia. Computed tomography scan revealed an enhanced mass accompanied with a cyst in the right cerebellar hemisphere. The mass situated in the subcortical region was removed. Histologically, highly vascular tumor cells lined the cavities. Postoperative radio- and chemotherapy were administered and the clinical symptoms improved gradually. Two months later, the patient complained of dyspnea. Chest X-ray on second admission demonstrated cardiomegaly. Hemorrhagic pericardial effusion amounting to 1000 ml was aspirated by pericardial puncture. Papillary clusters of tumor cells were demonstrated in the pericardial effusion. The patient died of cardiac failure. At necropsy solid tumors were located in the heart, lung, left inguinal region, and cerebellum. Histological diagnosis was mesothelioma arising from the heart. Primary pericardial mesotheliomas are rare; approximately 106 cases have been reported. Pericardial mesothelioma frequently spreads to the adjacent pleura and mediastinum, but distant metastases are extremely rare because patients with pericardial mesothelioma tend to die early due to cardiac failure or cardiac tamponade.

[Osteoid oteoma associated with intraosseous meningioma. A case report].

A very rare case of intraosseous meningioma accompanied with osteoma is reported. A 57-year-old male was admitted with left chronic subdural hematoma and an operation was immediately performed. At the time of admission skull X-ray film showed a high density area in the right frontoparietal region. Postoperative CT scanning showed no abnormality at standard window, widths and levels or at higher window, widths and levels. 99m Tc MPP scinti gram showed increased activity in the right frontoparietal region. Tomography of the skull indicated hyperostosis involving all layers. This skull tumor was diagnosed as osteoma. At the second operation the osteoma was removed. There seemed to be no changes in the bone and underlying dura. Histological examination indicated multiple microscopic meningotheliomatous meningioma with psammoma bodies in Haversian canals, leading to the conclusion that this was osteoid osteoma. It is suggested that this case be designated as type Lopez II and that it raises some interesting points regarding histogenesis and development of meningioma.

[Intracranial pressure changes during sleep in man].

ICP being a very significant parameter of intracranial pathology, it needs to be recorded continuously. ICP of 7 cases of normal pressure hydrocephalus (NPH) and 6 postoperative patients, for whom relationship between REM sleep and ICP was under discussion, was monitored at night and recorded by Brock's method. Polygraphic records also were obtained. Increased ICP was related to REM sleep in 3 of 6 postoperative cases. In the remaining 3 cases, REM sleep could not be observed the first postoperative night, and ICP was lower and stable all night. This fact may be an effect of anesthetic drugs. NPH patients were divided into 2 groups by pressure profile during night recording of ICP. One group of 2 cases demonstrated irregular ICP during REM sleep while the other group of 5 cases did not. The former 2 cases showed neurological improvement after shunt operations. In NPH cases, ICP has significance in deciding whether surgery is necessary. It appears reasonable to suggest that the augumentation of ICP during REM sleep in cases of hydrocephalus and postoperative condition is related to an increase in cerebral blood flow and an exhaustion of the absorptive mechanisms of CSF.

[Clinicopathological studies of the vegetative state--distinction between the vegetative state and brain death].

10 cases showing vegetative state and 2 cases of brain death due to severe brain damage were observed and the differences of clinicopathological findings between both states were discussed. The cases of vegetative state can be divided into three groups, first is widespread lesion in the cerebral cortex, second is in the cerebral white matter and third is in the brain stem. While, the diffuse whole brain damage including the vegetative center of the central nervous system causes brain death. We should like to emphasize that the most important structure to maintain the human life is the vital center in the brain stem, and that a human being, in whom only those function can be preserved, is possible to be alive as vegetative state. Prognostic value of the EEG indicating quality of survival noted in early stage after severe brain damage has not so important as the flat EEG revealed in brain death.

[Monstrous cell in malignant gliomas--in relation to radiation and chemotherapy (author's transl)].

The pathological effects of irradiation and chemotherapy have been studied in 9 autopsy cases of malignant and low grade gliomas. The brains have been examined by means of the complete study technique. Many histological features have been related to surgery, grading of histological classification of gliomas, irradiation and chemotherapy. Following irradiation and chemotherapy, in addition to increased necrosis and vascular response, a variety of characteristics changes were observed in cell and nuclear morphology with prominent formation of monstrous cells in all of 5 malignant gliomas treated with nitrosourea. These monstrous cells had irregular and hyperchromatic multiple nuclei and showed cytoplasmic degeneration. These cells which had not direct relationship to vessels distributed both in the periphery of tumor or necrosis and in the white matter remote from the main tumor. These changes were more pronounced in autopsy than in biopsy. The features showed here indicate that the monstrous cells may appear due to the result of inhibition of tumor cell division at the late mitotic phase after irradiation and chemotherapy.

[Cerebral hemorrhage in a case of antiphospholipid antibody syndrome].

We describe a 36-year-old man with antiphospholipid antibody syndrome complicated by cerebral hemorrhage. In December 1991 he was brought to another hospital with sudden onset of left hemiparesis and status epilepticus. He had been well previously. A CT scan and MRI showed a cerebral hematoma located in the right frontoparietal region. Twelve days later he was transferred to our hospital. Although a CT scan, MRI, and cerebral angiography were repeated, they did not reveal any abnormality regarding an etiology. Only persistently abnormal finding in laboratory studies was positive for lupus anticoagulant and anticardiolipin antibody, i.e. antiphospholipid antibodies. There was no serological evidence of SLE or other autoimmune diseases. Stereotactic biopsy of the hematoma wall and scalp artery showed no abnormality. Based on above findings we conclude that antiphospholipid antibodies have played an important role for the hemorrhage. Antiphospholipid antibody syndrome should be considered in a case of an unexplained cerebral hemorrhage especially in a young and normotensive patient.

[Immunological monitoring of brain tumors--prognosis and cellular immunity of patients with brain tumors].

The usefulness of in vivo skin tests for reaction to purified protein derivative (PPD) and phytohemagglutinin (PHA) for assessment of cell mediated immunity was investigated among 31 patients with brain tumors. These included 22 gliomas and 9 metastatic brain tumors. Each patient was administered intradermal injections of 0.05 micrograms PPD and 0.5 micrograms PHA, and erythema was observed in each case. A positive reaction (erythema diameter greater than 10 mm) to PPD was observed in 8 (74%) of 11 low grade gliomas, 3 (27%) of 11 malignant gliomas and 6 (67%) of 9 metastatic brain tumors. A positive reaction (erythema diameter greater than 25 mm) to PHA was observed in 8 (74%) of 11 low grade gliomas, 4 (36%) of 11 malignant gliomas, and 6 (67%) of 9 metastatic brain tumors. In repeated PHA skin reaction tests conducted at intervals of one month, the reaction of the patients depended on their clinical state. Thirteen of the patients died. The PHA skin reaction of 7 of the 13 patients who survived for more than 6 months was all negative 6 months prior to death, and continued and repeated reaction tests did not result in a positive finding except for one patient with malignant glioma. In 10 of the 13, the PHA skin reaction was negative one month prior to death, and the final test result was negative for 11 of the 13.(ABSTRACT TRUNCATED AT 250 WORDS)

[Biochemical monitoring of postoperative glioma (author's transl)].

Extention of the survival period and suppression of the recurrence of neurological symptoms during postoperative progression free intervals have become the most important problems in the treatment of gliomas. In the outpatient clinic, neurological and neuroradiological monitoring, including sequential CT scans, are especially valuable. In addition to each conventional monitoring methods, immunological and biochemical monitoring methods have been introduced as precise and noninvasive methods. In this paper, wer have discussed about the biochemical monitoring. In biochemical monitoring cystic fluid was repeatedly obtained through Ommaya's reservoir and chemically analysed during the postoperative period of eight cases of glioblastoma showed complete remission either clinically or chemically during the monitoring period. Chemical progression, especially a gradual increase in LDH, was detected in three cases of anaplastic astrocytoma prior to the clinical and radiological deterioration. In the remaining two cases of glioblastoma, neither clinical nor chemical regression was obtained in spite of postoperative adjuvant treatments. In biochemical monitoring of gliomas, total cholesterol, LDH and LDH isozyme values of cystic fluid were especially valuable.

[Magnetoencephalographic localization of epileptic foci using a 37-channel biomagnetometer].

The magnetoencephalography (MEG) and electroencephalography (EEG) were recorded simultaneously from 10 normal subjects using a 37-channel biomagnetometer. No paroxysmal spikelike waveform was observed in MEG at rest with eyes closed. The MEG and EEG were recorded also from 16 patients with primary epilepsy and 24 patients with secondary epilepsy. The examination proved to be safe for both normal subjects and patients with epilepsy. Interictal spikes were observed in 27 cases during the examination. The percentage of spikes identified in MEG but not in EEG was found to be 2. 3% of all spikes. The foci of the spikes identified in MEG were localized and determined in 20 cases. In 10 patients with secondary epilepsy, the localization of the foci were compared with the lesion demonstrated by magnetic resonance imaging (MRI) or computerized tomography (CT) and with the findings of EEG. In 6 cases, the foci by MEG were consistent. In the 4 cases where the MEG foci did not correspond to the MRI or CT findings, MEG foci were supported by the findings of EEG. MEG allows three-dimensional localization and enables us to elucidate the propagation of paroxysms. MEG was very useful in diagnosing epilepsy.

[A case of aortitis syndrome associated with hypertensive intracranial hemorrhage (author's transl)].

A case of aortitis syndrome associated with hypertensive intracranial hemorrhage is reported. A 38-year-old female was admitted in 1980 suffering from hypertension and blood pressure difference between the left and right arms which had existed for 10 years. Two weeks prior to admission, she noticed weakness and numbness of the right arm and leg. She was orientated and alert at the time of admission. Her right upper and lower extremities could not function with full strength against resistance. Also, right hemihypesthesia and hemiparesthesia were present. Left arm systolic blood pressure was 195 mmHg. Her pulse was palpable in both radial arteries. CT scans revealed a small high density area in the posterior crus of the internal capsule with a slight mass effect. There was no ventricular dilatation. She was given conservative treatment, such as with antihemorrhagic and antihypertensive drugs, and was discharged with good recovery after three months. Various studies were performed during her hospital stay. Based on angiographic findings, the most probable diagnosis was an extensive type of aortitis syndrome. Hypertension resulted from narrowing of the abdominal aorta and the right renal artery. Pulmonary scintiscanning using 99mTc-macroaggregated albumin revealed that her pulmonary arteries were also involved. Aortitis syndrome is not infrequent, but intracranial hemorrhage following after aortitis syndrome is rare. This may be because the carotid artery is involved in a high incidence of such cases, and therefore the intracranial blood flow is disturbed in most cases. Although the left common carotid artery was involved in the subject case, hypertensive intracranial hemorrhage occurred in the left posterior crus of the internal capsule. In a case of aortitis syndrome, therapy resulting in recirculation to the carotid artery involved is generally carried out in order to improve poor intracranial blood flow. However, it is suggested that control of blood pressure is necessary to prevent intracranial hemorrhage in aortitis syndrome.

[Cytochemical study of Mg2(+)-ATPase and ALPase activity in human meningiomas].

Ultracytochemical features of microvessels and tumor cells of the human meningiomas were examined by light and electron microscopy with special reference to the distribution of Mg2(+)-ATPase and alkaline phosphatase (ALPase) activity on the walls of the vessels and tumor cell surfaces. Materials used were 4 cases of meningiomas, 2 of which were meningotheliomatous type, one fibroblastic type and one malignant meningioma respectively. For ultracytochemistry, specimens were quickly fixed in an ice-cold 0.1 M cacodylate buffer containing 8% sucrose (pH 7.2) for one hour and transferred to a substrate solution for detection of Mg2(+)-ATPase and ALPase. The preparations were incubated at 37 degrees C for 15-30 min in the medium described by Mayahara et al. for ALPase and for 15-20 min in the medium described by Wachstein and Meisel. The control samples were incubated in a medium containing 1 mM Bromotetramisole for ALPase and also in a substrate free medium for Mg2(+)-ATPase. At the light microscopy, Mg2(+)-ATPase and ALPase activities appeared to be mainly restricted to the capillary wall and around or in the tumor cell nest showing whorl formation. Both enzyme activities were negative in the control study. By electron microscopy, reaction products representing Mg2(+)-ATPase activity were distributed in the basolateral plasma membrane of the endothelial cells on the surface of the pericytes and on the surface of the tumor cells. Reaction products of ALPase activity located mainly on the abluminal surfaces of the endothelial cells and in some specimen on both luminal and abluminal surfaces of those cells. Intense reaction products were distributed evenly on all round surfaces of the tumor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

[An autopsy case of glioblastoma occurred in the region after lobotomy].

The authors describe an autopsy case of glioblastoma occurred after 38 years received lobotomy. The patient was a 72 year-old male, who received lobotomy at 34 year old against schizophrenia. CT scan taken at 72 year old showed irregular low density areas without mass effect in the bilateral frontal white matter adjacent to the anterior horn. After 4 months, the signs of intracranial hypertension were observed and his consciousness was disturbed abruptly. CT scan revealed ring enhancement with marked mass effect in the left frontal lobe. A biopsy specimen from the tumor showed a picture of anaplastic astrocytoma. Family rejected the remission maintenance treatment. The patient died 3 months later the onset. At autopsy, a large tumor occupied in the left frontal lobe was recognized. The tumor demarcated poorly from the cerebral tissue and invaded into the left anterior cingulate gyrus and the corpus callosum. Histologically, tumor cells composed of fibrillary, gemistocytic and multinucleated astrocytes. GFAP, NSE and vimentin were found in large cells. Histological diagnosis was glioblastoma. It was suggested that the tumor occurred from the region around a cyst of prefrontal lobotomy in the left frontal lobe. In the right frontal lobe, a large cyst in size of 30-18 mm was present in the centrum semiovale. The wall of cyst was composed of layer of glial scar tissue. The origin of the cyst was discussed.

[CSF dynamics following shunt operation, with special reference to the diurnal changes of CSF circulation].

The purpose of this study is to study the pathophysiology of the cerebrospinal fluid (CSF) formation and circulation after a ventriculoperitoneal shunt operation. With the CSF flowmeter we developed, the CSF flow rate in the shunt tube has been measured non-traumatically over a 24-hour period in six patients. These include both communicating and noncommunicating hydrocephalus patients with ages ranging from 20 to 70. There were three cases of ruptured intracranial aneurysm, one cerebral contusion, one hypertensive brain stem hemorrhage and one occlusion of the aqueduct sylvius. Intraventricular pressure was continuously recorded for 24 hours prior to the shunt operation in each case, and the pressure changes were compared with the measured CSF flow rates in the shunt tube. The flow rate fluctuated between 0.05 ml/min and 1.2 ml/min with the supine position and high flow rates were detected in the early morning. Each case showed its own rhythm of CSF flow fluctuation during a 24-hour period, and the changes were compatible with the intraventricular pressure. It is suggested that there may be a relationship between these changes and an increased cerebral blood volume during the REM sleep stage.

[Immunological monitoring of brain tumors--prognosis based on T-lymphocyte subpopulations and skin testing for delayed hypersensitivity].

We have already reported on the usefulness of the phytohemagglutinin (PHA) skin test and the purified protein derivative (PPD) skin test in predicting the prognosis of brain tumor patients. This paper outlines our investigation of T-lymphocyte subpopulations and analysis of their utilization. The cellular immunological states of brain tumor patients were examined by means of PHA and PPD skin tests, the blastogenic response of T-lymphocytes to PHA and the T-lymphocyte subpopulations. Our subjects consisted of 10 cases of glioma (8 astrocytoma, 2 ependymoma), 2 cases of meningioma, one of teratoma, one of hemangioblastoma and 4 of metastatic brain tumor. These were divided into 2 groups: the benign group, which included low grade astrocytoma, meningioma, teratoma and hamangioblstoma, and the malignant group which included malignant glioma and metastatic brain tumor. The T-lymphocytes were counted by monoclonal antibody assay using Ortho-mune T-lymphocyte monoclonal antibody (OK series). We then counted an analysis to determine metastatic brain tumor. The T-lymphocytes were counted by monoclonal antibody assay using Ortho-mune T-lymphocyte monoclonal antibody (OK series). We then conducted an analysis to determine whether or not the T-lymphocyte subpopulations could be of value in the prediction of the possible prognosis of patients. The results were as described below. Ratio of helper/inducer T-lymphocytes (OKT 4 positive cells: Th) to suppressor/cytotoxic T-lymphocytes (OKT 8 positive cells: Ts) were 1.78 +/- 0.18 in the benign group and 1.00 +/- 0.49 in the malignant group.(ABSTRACT TRUNCATED AT 250 WORDS)