Local extension of HMGB1 in atherosclerotic lesions of human main cerebral and carotid arteries.

High mobility group box 1 protein (HMGB1) is a non-histone chromosomal protein which is highly conserved, ubiquitous, and widely distributed. HMGB1 has multiple functions in the nucleus, including the maintenance of nucleosome structure, the regulation of gene transcription, and involvement in DNA recombination. HMBG1 is currently recognized to have a wide range of potential functions and pathological relevance. HMGB1 is released into the extracellular space from necrotic cells and from activated macrophages. HMGB1 binds to the receptor for advanced glycation end products, resulting in the induction of inflammatory cytokines, and to endothelial cell thrombomodulin. HMGB1 neutralization may also reduce the development of atherosclerosis and ameliorate brain infarction. We investigated the immunolocalization of HMGB1 in atherosclerotic lesions of human cerebral and carotid arteries using a specific antibody, and confirmed the detailed expression and cell type localization using double immunofluorolabeling. In the main cerebral arteries, this anti-HMGB1 antibody intensely immunolabeled both normal morphological vascular smooth muscle cells (VSMCs) within the tunica media and infiltrating VSMCs within the intima of thickened fibrous cap plaques. Endothelial cells were also positive for HMGB1. In carotid plaques, HMGB1-like immunoreactivity (IR) was intense in macrophages, although this IR decreased with increasing cell size. Medium-sized foam cells (50-150 µm) were the most intensely stained. This IR was also observed in the nuclei of foam cells and VSMCs. These findings may provide a basis for understanding the association of HMGB1 with atherosclerotic lesions of the cerebral and carotid arteries, and for constructing strategies to counteract atherosclerosis with anti-HMGB1 antibody.

Neuroendoscopic trans-third ventricle approach for lesions of the ventral brainstem surface.

Due to the establishment in recent years of neuroendoscopic third ventriculostomy (ETV), it has become possible during ETV to observe the ventral brainstem surface--particularly the prepontine cistern--in a minimally invasive manner via the third ventricular base with a neuroendoscope. As an adaptation of that technique in this study, we investigated a neuroendoscopic trans-third ventricle approach (ETTVA), which accesses lesions of the ventral brainstem surface with a neuroendoscope inserted via the stoma of the third ventricular floor. Our study included 6 cases, including one case each of neurenteric cyst, chordoma, pontine glioma (astrocytoma), ecchordosis physaliphora, endodermal cyst, and cystic schwannoma. Surgical operations performed by ETTVA included 3 cases of tumor resection, 2 cases of tumor biopsy, and 1 case of cyst puncture and aspiration. There were no complications accompanying ETTVA. Out of the 6 cases, only 1 required additional surgical treatment following ETTVA surgery. In the other 5 cases, no additional surgical procedures were performed. This study showed that ETTVA allowed access to the prepontine cistern quickly and in a minimally invasive manner. In selected cases, ETTVA can offer a new approach to these lesions.

Fourth ventricular meningioma in an adult--case report.

A 72-year-old female presented with an intra-fourth ventricular meningioma manifesting as truncal ataxia. Computed tomography (CT) showed a slightly high-density, well-demarcated, and homogeneously enhanced mass located in the fourth ventricle and extending to the right lateral recess. T2-weighted magnetic resonance (MR) imaging revealed a peritumoral high-intensity band without dural tail sign. Bilateral vertebral angiography revealed faint tumor staining supplied from the choroidal branches of the posterior inferior cerebellar arteries. The mass was totally resected via a suboccipital approach. CT, T2-weighted MR imaging, and vertebral angiography are informative for the preoperative diagnosis of fourth ventricular meningioma.

Primary intracranial malignant schwannoma of trigeminal nerve. A case report with review of the literature.

The authors report a rare case of primary intracranial malignant schwannoma of the trigeminal nerve occuring in a 30-year-old woman without von Recklinghausen's neurofibromatosis (VRNF). The tumour arose from the intracranial part of the left trigeminal nerve, without skull base destruction. The tumour was partially removed operatively, followed by focal 50 Gy irradiation, but unfortunately the tumour showed rapid regrowth. A second operation was attempted, but she died of cerebral infarction soon after operation. Histologically, the original tumour was characterized by the presence of foci of extremely high cellularity, pleomorphism and mitosis in an otherwise typical benign schwannoma. Immunohistochemically, the tumour cells were positive for S-100 protein even in the atypical areas, suggesting the tumour to be of Schwann cell origin. However, the recurrent tumour was composed of undifferentiated spindle cells, which were negative for S-100 protein. Thus, it is possible to consider that the S-100 protein expression could reflect the degree of differentiation of Schwann cells. Furthermore, the postoperative irradiation might have exacerbated the malignant progression in the present case.

Sex ratios and genetic variation in a functionally androdioecious species, Schizopepon bryoniaefolius (Cucurbitaceae).

Androdioecy, coexistence of hermaphrodites and males, is an extremely rare breeding system in angiosperms. In the present study, Schizopepon bryoniaefolius (Cucurbitaceae) was confirmed to be functionally androdioecious based on observations of floral and pollen morphology and bagging experiments. Six out of the 11 studied populations consisted of only hermaphrodites, while the other five populations were androdioecious and the frequencies of males were consistently lower than those of hermaphrodites (5.5-28.3%). To understand the consequences of an androdioecious breeding system, genetic variation was estimated using four polymorphic allozyme loci. The degree of genetic differentiation among 11 populations was high (G(ST) = 0.688). Inbreeding coefficients (F(IS)) for all loci significantly deviated from zero. In particular, the F(IS) values averaged across the polymorphic loci in hermaphrodite populations were close to unity, suggesting that hermaphrodites are predominantly selfing in the absence of males. A significant negative correlation was found between the frequencies of males and inbreeding coefficients, indicating that outcrossing rates depend on the population sex ratio.

Primary meningeal malignant fibrous histiocytoma with cerebrospinal dissemination and pulmonary metastasis.

Primary intracranial malignant fibrous histiocytoma (MFH) is very rare, and not much is known about its clinical features. The authors report a case of left temporal leptomeningeal MFH, with consequent cerebrospinal fluid (CSF) dissemination and pulmonary metastasis. The clinical features of this case and the therapeutic prognosis of 17 cases reported previously in the literature were reviewed.

[Clinical features and treatment of sarcoidosis involving the central nervous system].

PURPOSE: The purpose of this study was to investigate the clinical features, diagnosis, and treatment modalities of three cases with neurosarcoidosis, which involved the central nervous system (CNS). CASES: Three men with neurosarcoidosis, aged 27, 29 and 60 years, are presented. Two of them had previously been given a diagnosis of sarcoidosis. The clinical symptoms of these cases included diabetes insipidus, pituitary dysfunction, seizure, mental disorder, visual field disturbance and pyramidal tract signs. In these cases, CT scan and MRI showed the presence of a tumor near the pituitary gland, diffuse nodules in the subarachnoid space or meningoencephalitis associated with angitis. The level of angiotensin converting enzyme (ACE) in the sera and in the cerebrospinal fluid, were elevated in the two cases who had no brain biopsy. All three cases were treated with steroids; two of them received pulse steroid therapy. RESULTS: The two cases who received pulse steroid therapy responded quickly, with improvement in clinical features, serum ACE levels and neuroradiological findings. Under oral administration of steroids, all three cases recovered with complete remission of neurosarcoidosis except for endocrinological symptoms. DISCUSSION: The main pathological changes of neurosarcoidosis are granulomatous angitis of the venular walls and occasionally, of the capillaries near the meninx and Virchow-Robin space. The patients also had symptoms of secondary meningoencephalitis. These changes were mainly located in the hypothalamus and pituitary gland. The patients had complex symptoms resulting from endocrine system granuloma, as well as from cerebral ischemia. The severity of the disease and effectiveness of treatment, can be evaluated by measuring ACE levels in the cerebrospinal fluid (over 1. 0 IU/l), and by Gd-enhanced MRI. Early pulse steroid therapy with subsequent oral steroid administration is thought to be important for neurosarcoidosis treatment, in order to prevent irreversible damage in the CNS.

[A surgical case of ecchordosis physaliphora].

The authors report a rare case of ecchordosis physaliphora (EP) in the prepontine region. A 51-year-old woman was admitted with a small cystic mass in the prepontine region, complaining of headache and an episode of transient double vision. Plain X-ray and lateral tomography films showed a protrusive hyperostosis at the middle clival region. The CT scan showed no abnormal densities in the retroclival region, and CT cisternography showed an isolated small round mass in the prepontine cistern. A small cystic mass with no enhancement with Gd-DTPA was revealed on MRI, mildly compressing the basilar artery and the rostral surface of the pons. The totally excised mass was pedunculated and was contiguous with the dorsal wall of the clivus via a small dural defect. The histologic diagnosis was EP, consisting of scattered physaliphorous cell nests, which were not positive for MIB-1 staining. The pedicle consisted of mature cartilaginous cells. The authors briefly reviewed the few previously reported cases of symptomatic EP and intradural chordoma, and discussed the differences between them. The histological features, especially the proliferation potential, may be pathognomonic. The histogenesis and the clinical features of symptomatic EP are also provided.

[Histogenesis of central neurocytoma: an immunohistochemical and electronmicroscopic study of four cases].

Four intraventricular central neurocytomas were studied histopathologically and intriguing findings were obtained with regard to the histogenesis of this tumor. The cases included 3 males and 1 female aged 17-25. The tumors had developed in the regions from the lateral to the third ventricles and were surgically removed in all the cases. A honeycomb appearance was recognized on H&E staining, and the calcification and latticed vascular findings closely mimicked the appearance of oligodendroglioma. A characteristic wide eosinophilic fibrous stroma was observed frequently. Immunohistochemically, all four cases were NSE-positive and strongly synaptophysin-positive, and by electronmicroscopy, neurosecretory granules and microtubules were observed in all cases and typical synapse structures in 2 cases. GFAP immunoreactivity and glial differentiation, including ependymal cells were exhibited electronmicroscopically, such as glial fibrils, basal bodies, centrioles and 9 + 1 patterned cilia-like structures in 2 cases. These findings suggest that central neurocytoma is an embryonal tumor in the wide sense, originating from the germinal matrix cell of the lateral ventricles and possessing multipotency, with potent differentiation from mature neurons.

[Cystic ectopic pituitary adenoma: report of a case].

A 68-year-old man was admitted with suprasellar cystic tumor with obstructive hydrocephalus, and complaining of slowly progressive memory disturbance, gait disturbance and urinary incontinence. Neurological examination revealed bilateral visual disturbance and disorientation. Skull X-ray films revealed no dilatation of sella turnica and mild erosion of the dorsum sellae. A cystic suprasellar tumor was revealed extending upward to the third ventricular floor and the solid part of the tumor was homogeneously enhanced with Gd-DTPA on MRI. The T1-weighted sagittal MR image revealed a normal pituitary gland and the diaphragma sellae below the tumor. The tumor was totally removed via a bifrontal basal interhemispheric approach, and the tumor was attached to the pituitary stalk and was not contiguous with the pituitary gland. The histological diagnosis was sinusoidal type of chromophobe and non-functioning adenoma. Postoperative MRI revealed a preserved normal pituitary gland and the stalk. To our knowledge, only 11 cases of suprasellar ectopic pituitary adenoma have been reported. We reviewed their neuroradiological features and discussed the pathogenesis. In particular, cystic and nonfunctioning suprasellar ectopic pituitary adenoma may be difficult to distinguish from craniopharyngioma.

A case of cerebellar neuroectomesenchymoma in an infant.

This case report concerns a congenital cerebellar tumor in an infant. The tumor consisted of small, immature lymphocyte-like cells, medium-sized, rhabdoid cell-like cells, and large, polymorphic gemistocytic astrocyte-like cells, which were admixed in motley form on a background of neuronal matrix and dural and collagen fibrous tissues. Immunohistochemical studies revealed that the cytoplasm of rhabdoid cells had conspicuous structures, resembling weakly eosinophilic homogeneously amorphous inclusion bodies, and that the strongly eosinophilic cytoplasm, seen abundantly in the gemistocytic astrocyte-like cells, was a mixture of components that were positive for glial fibrillary acidic protein (GFAP) and vimentin and of components positive for myoglobin. Because of the simultaneous expression of both, neuroectodermal and mesenchymal characteristics the reported tumor was not a mixed tumor of independent neuroectodermal and mesenchymal tumor components, but a very rare neuroectomesenchymoma derived from immature cells with pluripotential differentiating capabilities.

[GH-secreting pituitary adenomas--correlation between clinical features, growth potential and histopathological studies].

We compared clinical features, including endocrinological and radiological findings, histological features and the proliferative parameters (PCNA, MIB-1 and AgNORs) with immunohistochemical features in growth hormone (GH) secreting pituitary adenomas. 18 cases were divided into two groups based on immunohistochemical intracytoplasmic stainings for cytokeratin: a prominent dot-like pattern (group I, 6 cases) and a diffuse perinuclear pattern (group II, 12 cases). Patients in group I (6 females, m = 37.6 years old) were younger, showed female predominance and had a shorter history of acromegaly compared with patients in group II (7 males, 5 females, m = 44.9 years old). Although the size of the adenomas tend to be larger in group I, no difference was recognized in plasma GH levels between the two groups. Increased serum prolactin (PRL) levels were accompanied more common in group I. Abnormal GH responses to TRH and LHRH injection and GH suppressions to bromocriptine administration were more frequently noted in group II than group I. Surgical approaches were transcranial in most cases of group I and transphenoidal in group II. There was no difference in surgical results as to the correction rate of GH levels between the two groups. Histopathologically, group I adenomas were mostly chromophobic, weakly positive for GH, and were generally negative for PRL and alpha-subunit. On the other hand, group II adenomas were mostly acidophilic, diffusely stained for GH, and were often positive for PRL and alpha-subunit. However, there was no significant difference in proliferating parameters between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

[Immunohistochemical study of glutamine synthetase expression in normal human brain and intracranial tumors].

Specific expression in brain astrocytes, glutamine synthetase (GS) is considered to be an indicator of cell activity, owing to its functional significance. Glutamine, its enzymic reaction product, has been found to be a precursor of nucleic acid and purine, suggesting some sort of involvement in astrocyte differentiation and proliferation. So, we conducted immunohistochemical analysis of GS in normal autopsied brain and brain tumor tissue, using anti-GS antibody. In the normal brain, GS-immunoreactivity was marked in granular form in the cerebral cortex from the second layer to sixth layers, the cerebellar granular layer, and the astrocyte bodies and projections in the Purkinje layer, but its manifestation in the cerebral white matter was extremely poor. GS was not present at all in ventricular ependymal cells and choroid plexus epithelial cells. In the primary brain tumor, GS-immunoreactivity was seen only in the astrocytoma cells. An inverse correlation between histological malignancy and degree of GS expression was observed. Otherwise, GS was expressed only in the metastatic brain tumor cells and the craniopharyngioma epithelial cells. GS expression pattern in the normal brain reflected innate function through its pronounced presence in the astrocytes, where glutamic acid-transmitting synapse were abundant. This finding together with the histological malignancy-related expression of GS in the astrocytomas suggest that it could be not only a useful marker for pathologic tumor diagnosis but also useful for evaluating the functional cataplasia of tumor-composing cells or their potential of proliferation.

Immunohistochemical study of glutamine synthetase expression in early glial development.

Early glial development in the brains of rat embryos was immunohistochemically studied using antibodies to two kinds of glial-specific proteins, glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP). The results showed that GS was first expressed in the ependymal lining of the ventral side of the neural tube in the cervical segment on Embryonic Day 14 and then in the radial glia radiating from the neural tube on Embryonic Day 16. Subsequently, GS-positive glia cells increased in number with time. On the other hand, GFAP was first expressed in the fimbria hippocampi and the pial surface on Embryonic Day 18, but no marked evidence of GFAP expression was noted in the GS-positive radial glia. These results suggested that a specific protein is expressed at each stage of early glial development. Since the radial glia was positive for GS, it was thought that GS-mediated neuronal-glial interactions may play an important role in the development of the central nervous system.

[Mouse fetal brain specific protein "GP68" is expressed in human tumor cells].

It is well known that some fetal antigens are expressed in malignant tumor cells. Likewise, brain tumors, especially histologically malignant cases, may have any antigenic relationships with fetal brain. So, we investigated the relationship by immunohistochemical technique, utilizing a polyclonal antibody to mouse fetal stage-specific polypeptide "GP68". We prepared GP68 from homogenate of head part of embryos at the 14th day of gestation mice by RCA-1 agarose column chromatography. And immunized it to Japanese white rabbits and the titer was measured by enzyme-linked immunosorbent assay. We analyzed operatively resected brain tumors and autopsy brain tissues. Frozen tissues were fixed in cold acetone and immunostained with anti-GP68 serum according to biotin-streptavidin peroxidase method. Remained tissues were homogenized in Laemmli's sample buffer and electrophoresed. The proteins were transferred to nitrocellulose membrane and immunostained with anti-GP68. Normal brain tissues were not positively stained, except for capillary endothelium which showed a weak staining. On the other hand, brain tumors of neuroectodermal origin were positively stained in varying degrees, and other tumors were negative. It is especially noteworthy that, in astrocytoma cases, there exists a definite correlation between the intensity of stain and the degree of histological malignancy. Immunoblot studies demonstrated a very weak band at 68 KD in normal brain and meningioma. In contrast, very strong band at the same position was seen in malignant astrocytomas. These results suggested that in brain tumors, especially those of neuroectodermal origin, GP68 antigen is expressed and the degree of expression is related to their histological malignancy. So this fetal antigen may be useful for evaluation of biological malignancy of gliomas.(ABSTRACT TRUNCATED AT 250 WORDS)

[Intracranial hematoma accompanying bleeding tendency: therapeutic practice and analysis of literature].

Therapies and prognoses covering fifteen cases of intracranial hematoma (ICrH) accompanying various types of bleeding tendency (BTD) were studied along with a secondary analysis of the pertinent references. Fifteen cases were divided into two groups, Group A comprising 11 cases of ICrH accompanying primary BTD, and Group B comprising four cases of ICrH accompanying secondary BTD caused by various underlying diseases. Group A included four cases of hemophilia A (Hp-A), two cases of factor XIII deficiency (FXIII-d), three cases of thrombocytopenia (Th-p) and two cases of vitamin K deficiency (VK-d). The four cases of Hp-A responded favorably, with good prognoses, to a supplementary therapy alone. This result was endorsed by the development of therapy as documented in the references. The combined five cases of FXIII-d and Th-p tended without exception, to show good prognoses in the wake of a combination therapy of supplementary treatment and surgical procedure. As regards FXIII-d, there was an inter-reference difference in supplementary doses. Many references shared the view that splenectomy was essential to the treatment of Th-p in general, and idiopathic thrombocytopenic purpura in particular. The current study also suggested that gammaglobulin in large doses would serve as an effective therapy. The two cases of VK-d suffered from a serious degree of lingering neurologic manifestations, although their lives were saved. Even though there is an established therapy for it, VK-d was found to be a problem with poor functional prognosis showing the importance of the preventive approach. Group B was classified into the acute type and the subacute type depending on the rate of pathologic development. As underlying diseases DIC and myelofibrosis due to acute myeloblastic leukemia, and Th-p due to aplastic anemia were noted in two cases in each group. Of these, two cases of the subacute type were able to be saved, while two cases of the acute type followed poor prognostic courses resulting, eventually, in death. The following were found to be responsible fatal factors: 1) causes of BTD which involved both mechanisms of coagulation and hemostasis, 2) non-removal of the underlying disease, in which case supplementary therapy tended to be futile, and 3) the underlying disease per se as a danger to the life of the patient. In conclusion, therapeutic rationale and prognosis in ICrH accompanying primary type of BTD will benefit from the implementation of an adequate augmentative therapy as in the ordinary type of ICrH.(ABSTRACT TRUNCATED AT 400 WORDS)

[Acute myelogenous leukemia accompanied by HTLV-I associated myelopathy (HAM) caused by blood transfusion].

A case of AML accompanied by HTLV-I associated myelopathy (HAM) is reported. A 37-year-old woman was admitted to our hospital in April 1985 because of severe anemia, general malaise and fever. On admission, anemia, thrombocytopenia and leukocytosis consisting of 32% myeloblasts and 6% promyelocytes were noted. A bone marrow study revealed marked myeloid hyperplasia, and a diagnosis of acute myelogenous leukemia (M2) was made. In order to improve the patient's severe anemia and thrombocytopenia, a large amount of blood transfusion was applied at once. Thereafter BHAC-DMP therapy was commenced resulting in complete remission 3 months after initiating chemotherapy. Hematological improvement has continued (as of May 1988). In June 1986 the patient showed a gait disturbance of slowly progressive course. Neurological examination revealed hyperactive knee and ankle jerks with a positive Babinski's sign, and foot clonus were also noted bilaterally. Sphincter impairment was detected. A CSF sample contained slight pleocytosis with some abnormal lymphocytes similar to those found in adult T cell leukemia. Antibodies to HTLV-I were found in the CSF and serum by EIA method. According to these findings we diagnosed the patient's illness as HAM, referring to the new clinical entity named by Osame. This patient had undergone a blood transfusion 14 months before the onset of this myelopathy, therefore the transmission of exogenous antigens through blood transfusion may be the cause of HAM. Corticosteroid pulse treatment was administered and striking improvements countering gait disturbance resulted in this patient.