bluuebunny/crossref_metadata_2025 huggingface dataset:
High densities of tumor necrosis factor‐α in the cerebral cortex and basal ganglia in human immunodeficiency virus‐1‐associated cognitive/motor complex: A quantitative regional analysis study
Authors: Kobayashi Katsuji , Seilhean Danielle , Uchihara Toshiki , Duyckaerts Charles , Hauw Jean‐Jacques
Published: May 2007

This study determined the regional distribution of tumor necrosis factor‐alpha (TNF‐α)‐positive cells in HIV‐1‐infected brains and controls, and evaluated its correlation to cognitive impairment in HIV‐1‐associated cognitive/motor complex (HCMC) using TNF‐α and glial fibrillary acidic protein (GFAP) double immunohistochemistry. The TNF‐α‐positive cell density in the cerebral cortex and basal ganglia was significantly increased in patients with HCMC compared with that in HIV‐1‐seropositive nondemented patients (non‐HCMC), and the basal ganglia TNF‐α‐positive cell density was significantly correlated with Mini‐Mental Status Examination (MMSE) score. Glial fibrillary acidic protein‐positive astrocytes were significantly increased in density compared with normal controls, but no significant difference between HCMC and non‐HCMC patients was obtained. The density of GFAP‐positive astrocytes and TNF‐α‐positive cells was well correlated other than in the basal ganglia. The basal ganglia TNF‐α‐positive cell densities showed a significant correlation with MMSE scores. The result suggests that the significantly high content of TNF‐α‐positive cells in the cortex and basal ganglia is a neurochemical feature characteristic of HCMC. The significant correlation of the basal ganglia TNF‐α‐positive cell density with degree of cognitive impairment might be associated with subcortical dementia during HIV‐1 infection.
Immunohistochemical detection of tau protein in various non‐human animal brains
Authors: Kuroki Koji , Uchida Kazuyuki , Kiatipattanasakul Wijit , Nakamura Shin‐ichiro , Yamaguchi Ryoji , Nakayama Hiroyuki , Doi Kunio , Tateyama Susumu
Published: May 2007

In order to clarify the tau phosphorylation in aged non‐human animal brains, paraffin sections of human and non‐human animal brains were examined immunohistochemically using two antibodies against tau. The monoclonal antibody (mAb) tau‐2 is known to bind non‐phosphorylated and phosphorylated forms of tau protein and to recognize neurofibrillary tangles (NFT) in the human brain, whereas rabbit antiserum against tau recognizes the protein in a wide variety of mammalian species. In this study, both antibodies recognized axons, neurites, and cytoplasm of neuronal cells together with oligodendrocytes in non‐human animal brains as reported in human brains, suggesting that the distribution of normal tau is quite similar between human and non‐human animal brains. Neurofibrillary tangles detected by the Gallyas method were not found in non‐human animal brains. Tau‐2 intensely labeled NFT in the human brain and neurons of brain stem nuclei in the canine brain. The results may suggest very early stage of abnormal tau phosphorylation leading to NFT formation in the aged canine brain. It is probable that phosphorylation develops over a long period of time (more than 25–30 years) and as a result abnormal tau becomes apparent in humans because they have a long life‐span in comparison with most non‐human animals.
Correlation between glioblastoma cell infiltration and T2 prolongation on magnetic resonance imaging
Authors: Tamura Masaru , Zama Akira , Kurihara Hideyuki , Ono Nobuo , Kano Tomoaki , Imai Hideaki , Ishiuchi Shougo , Nakazato Yoichi
Published: May 2007

Tumor cell infiltration around the tumor tissue in glioblastoma was investigated in 13 patients with glioblastoma who underwent gross total tumor removal. Thirty‐four glioblastoma cases were operated on between January 1988 and December 1995. T1‐weighted magnetic resonance imaging (MRI) with gadolinium enhancement was used to measure tumor size, and T2‐weighted MRI to detect perilesional edema. Biopsy samples of surrounding tissue taken after tumor removal were histologically examined. Small tumors (< 3 cm diameter) and moderatesized tumors with mild perilesional edema had no or few infiltrating tumor cells in the surrounding tissue. In contrast, large tumors (> 6 cm diameter) with moderate or high perilesional edema had intensive tumor cell infiltration.
Impairment of cathepsin B immunoreactivity in the hippocampal nerve cells with aging in the elderly: Possible evidence for dysfunction of lysosomal proteolysis in relation to the pathogenesis of Alzheimer's disease
Authors: Ii Kunio , Towatari Takae , Ito Masayuki , Ohama Eisaku , Hirano Asao
Published: May 2007

Immunohistochemical localization of cathepsin B (CB) in the hippocampal nerve cells was examined in patients ranging from age 18 days to 82 years to examine the change of proteolytic activity of nerve cells with aging through the CB immunoreactivity. Although it varied from case to case, region to region, and to some degree cell to cell, generally, CB immunoreactivity in the nerve cells was weak in the newborn, strong from age 7 to about 60, and decreased in most nerve cells, or the number of nerve cells with impaired CB immunoreactivity increased, after about 60 years of age. This suggests impairment of protein metabolism and/or dysfunction of lysosomal proteolysis in the nerve cells with aging. The last finding may be important as a background or preceding phenomenon that may cause abnormal protein metabolism relating to the formation of neurofibrillary tangles and/or senile plaques with aging and in Alzheimer's disease (AD). The involvement of CB in the metabolism of Aβ‐amyloid protein precursors (APP) and the possible close relation of presenilins to APP should also be considered.
Neovascular basement membrane and its significance in the biological behavior of astrocytic tumors
Authors: Takekawa Yoshinori , Sawada Tatsuo , Sakurai Isamu
Published: May 2007

The correlation between morphological changes of neovasculature in astrocytic tumors and tumor biological behavior, were studied using anti‐collagen type IV, von Willebrand factor and Ki‐67 (MIB‐1). Forty‐four astrocytic tumors were histologically classified into Grade 1 (G1) to 4 (G4), according to the Daumas‐Duport classification. To evaluate quantitative changes of the basement membranes (BM) of neovasculatures, the most significantly altered location was chosen and four morphological changes were used as morphological criteria: dissociation, fusion, glomeruloid change and thickening. Basement membrane grades were determined according to these criteria as encountered on the sections. If none of the criteria was found (such as in vesssels in the normal brain) a BM grade 1 (BM‐1) was given, BM‐2 was used when one of the four criteria was noted, BM‐3 for two, BM‐4 for three, and a score of BM‐5 was assigned if all four morphological changes were noted. All cases of G1 and G2 corresponded to BM‐1 or BM‐2; all cases of G3 corresponded to BM‐3; and all cases of G4 corresponded to BM‐4 or BM‐5. Microscopic angiogenesis grading system (MAGS) scores and endothelial Ki‐67 labeling index (eKi‐67 LI) were also correlated with histopathological grading. Significant differences between eKi‐67 LI and MAGS scores were identified among each BM grade, but not between BM‐2 and BM‐1. It is important for tumor grading and behavior to evaluate the degree of morphological changes of BM in astrocytic tumors, especially fusion and glomeruloid change.
Degeneration of spinal dorsal root ganglia in adult rats treated with methylmercury: Chronological observations on the cell bodies, centrally directed axons and presynaptic terminals
Authors: Su Mu , Kakita Akiyoshi , Wakabayashi Koichi , Yamada Mitsunori , Takahashi Hitoshi , Ikuta Fusahiro
Published: May 2007

In order to elucidate the degenerative process of the central, i.e. ascending, axons and of the spinal dorsal root ganglion (DRG) neurons caused by methylmercury (MeHg) intoxication, we performed chronological ultrastructural observations in rats given 10 mg/kg per day of MeHg on consecutive days and sacrificed on days 5, 6, 7, 9, 11, 12 and 16 (day 1 was the day the first dose was administered; maximum 10 days). On day 5, the distal axons and presynaptic terminals in the gracile nucleus showed dystrophic changes manifested by accumulation of mitochondria, dense bodies and irregularly branching tubular structures, but no abnormalities were detected in the cell bodies in the DRG or the proximal axons in the gracile fascicle. From day 7 onward, cell body degeneration and loss became apparent, followed by anterograde degeneration of the proximal axons. These findings indicate that in MeHg intoxication, the distal portions, including the presynaptic terminals, of the centrally directed axons of the DRG neurons are affected first, but the subsequent pattern of progressive degeneration is not consistent with the dying‐back process. We consider that this initial axonal change reflects the preceding subtle biochemical derangements in the cell bodies.
Basal ganglia lesions in corticobasal degeneration differ from those in Pick's disease and progressive supranuclear palsy: A topographic neuropathological study of six autopsy cases
Authors: Tsuchiya Kuniaki , Uchihara Toshiki , Oda Tatsuro , Arima Kunimasa , Ikeda Kenji , Shimada Hiroyuki
Published: May 2007

The distribution of the lesions of the basal ganglia including the striatum, pallidum and subthalamic nucleus were investigated neuropathologically in six Japanese autopsy cases of corticobasal degeneration (CBD) using routine staining including the hematoxylin‐eosin (HE) and Holzer methods. We compared the distribution of these lesions with those reported in Pick's disease and progressive supranuclear palsy (PSP). The lesions were classified as mild, moderate or severe. The extent and distribution of basal ganglia lesions in all six cases was uniform: the pallidum showed severe lesions, the striatum moderate lesions, and the subthalamic nucleus mild lesions. In CBD, the degree and distribution of the lesions within the basal ganglia differed from those reported for Pick's disease and PSP; in Pick's disease the lesions of the striatum are more prominent than that of the pallidum, and in PSP the involvement of the subthalamic nucleus is more pronounced than that of the striatum. These neuropathological findings have implications for the morphological differential diagnosis among Pick's disease, CBD, and PSP.
Presenilin‐1 polymorphism and neuropathological lesions of aging brain and late‐onset Alzheimer's disease
Authors: Uchihara Toshiki , Helbeque Nicole , Amouyel Philippe , Duyckaerts Charles , Hauw Jean‐Jacques
Published: May 2007

In addition to missense mutations of the presenilin‐1 gene, an association between a polymorphism within the intron 3’to exon 8 and late‐onset sporadic Alzheimer's disease (AD) cases has been reported. This study examined the relationship between this polymorphism and the density of lesions by studying a homogeneous group of cases with different levels (normal to severely demented) of intellectual impairment. There were no differences in age and intellectual status between the groups of different genotypes. In all areas of the brain examined (frontal, temporal, calcarine, supramarginal and subicular areas), we found no difference in the density of Aβ‐deposits. Only in the subicular area, a lower density of neurofibrillary tangles (NFT) was found in the 2/2 genotype group compared with those found in the combined group of 1/1 and 1/2 genotypes. This suggests that this polymorphism influences the development of NFT preferentially detected in the subiculum, where prominent AD lesions are usually observed.
Olivopontocerebellar atrophy of neonatal onset with muscle hypertonia in two siblings
Authors: Iso Ayako , Ozawa Hiroshi , Kurokawa Toru , Kubota Masaya , Mori Kazuo , Takashima Sachio
Published: May 2007

Two siblings (one girl and one boy) with familial infantile olivopontocerebellar atrophy (OPCA) are reported. The brain pathology in one child revealed marked hypoplasia of phylogenetically new parts of the pons and medulla (pontine nuclei and inferior olivary nuclei) associated with hypoplasia of the neocerebellum. The clinical features were severe muscle hypertonia, hyperreflexia, multiple joint contractures, failure to thrive and respiratory insufficiency. Laboratory examinations including hematology, blood chemistry, very long chain fatty acids, analysis of amino acids in serum and urine, and organic acids in urine, and chromosomal analysis, revealed no abnormalities. The diagnosis of OPCA was established prior to death by magnetic resonance imaging (MRI) in one child. These cases may be atypical because the corticospinal tract and dentate nucleus were involved, in addition to OPCA.
A case of Werdnig‐Hoffmann disease showing extensive sensory involvement after prolonged mechanical ventilation
Authors: Kuroiwa Toshihiko , Kuwata Takeshi , Okeda Riki , Asou Seijiro , Nonaka Ikuya , Ichinose Shizuko , Takemura Tamiko
Published: May 2007

A 5‐year‐old boy with Werdnig‐Hoffmann disease (WHD), who had been mechanically ventilated for the majority of his life, was examined pathologically. In addition to the classic features of WHD, extensive sensory involvement, including pronounced glial bundle formation in the posterior nerve root, severe demyelination of the posterior column in the whole spinal cord and thalamic neuronal loss were observed. Mechanical ventilation for 5 years prolonged the patient's survival beyond its natural course and produced the unusual pathological findings such as the phrenic motoneuronal loss and severe diaphragmatic and intercostal muscle atrophy. This also appeared to be responsible for the extensive sensory involvement. Data from this case and from previous reports show that WHD is a potential multisystem disorder affecting primarily, but not exclusively, the motor system. We observed marked neuronal accumulation of eosinophilic intracytoplasmic granules in the oculomotor nucleus, substantia nigra, locus ceruleus and nucleus raphe pontis, which appeared as intramitochondrial electron‐dense granules on electron‐microscopy and myoglobin‐positive granules by immunostaining.
Heterotopic neurons in congenital myotonic dystrophy with mental retardation
Authors: Watanabe Chigusa , Katayama Sadao , Noda Koichi , Kaneko Mayumi , Inai Kouki , Nakamura Shigenobu
Published: May 2007

We studied heterotopic abnormalities of the brain and spinal cord of a 48‐year‐old mentally retarded man with congenital myotonic dystrophy. He presented with a 2‐year history of progressive muscular weakness in the trunk and he developed dyspnea on effort and orthopnea 4 months pro to death. He died of acute renal failure and severe congestive heart failure. The characteristic neuropathological finding was a number of heterotopic neurons in the cerebrum. In the molecular layer of the cerebral cortex, medium‐sized neurons, pyramid‐shaped large neurons, and horizontal cells were noted. Many neurons were also distributed sporadically in the subcortical white matter. In the spinal cord, abnormally situated neurons were present in be posterior and lateral columns near the gray matter. These findings suggest that intrauterine maturational disturbance occurs during the period of migration and organization of neurons in the brain and spinal cord.
Ballooned neurons in corticobasal degeneration and progressive supranuclear palsy
Authors: Mori Hideo , Oda Masaya
Published: May 2007

We examined the distribution and immunohistochemical characteristics of ballooned neurons (BN) in the cortex of patients with corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). In CBD, the BN were distributed mainly in the medial and superior areas of the frontal cortex, such as the cinglate cortex, superior frontal cortex, and precentral cortex. In six of the nine patients with PSP studied, BN were seen in the cerebral cortex. In two of these six patients, BN were abundant and cortical degeneration was present in the precentral cortex. On immunohistochemical examination, BN were positive for phosphorylated neurofilament protein (pNFP) and αB crystallin, and some BN were positive for ubiquitin and tau protein. On double immunohistochemical staining, all pNFP‐positive neurons were stained with anti‐αB crystallin antibody, whereas some αB crystallin‐positive BN were not stained by anti‐pNFP antibody. The presence of cortical BN does not differentiate PSP from CBD, although BN are sparse in patients with PSP when cortical degeneration is not present. The results of the double immunohistochemical staining suggested that αB crystallin might be expressed earlier than pNFP in the formation of BN.
Familial amyotrophic lateral sclerosis and Cu/Zn superoxide dismutase mutation
Authors: Shibata Noriyuki , Kobayashi Makio
Published: May 2007

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder that involves mainly the motor neuron system. Five to 10 percent of the ALS cases are familial; most others are sporadic. Several mutations in the superoxide dismutase‐1 (SOD1) gene have recently been shown to be associated with about 20% of familial ALS patients. The reduced enzyme activity of many mutant SOD1 points to the possibility that a loss‐of‐function effect of the mutant enzyme is responsible for the pathogenesis of the disease. However, this conflicts with the autosomal dominant inheritance of SOD1 mutation‐associated ALS and the normal SOD1 activity in homozygous patients in a SOD1‐linked ALS family. Current biochemical investigations have provided evidence that mutant SOD1 may catalyze the peroxynitrite‐mediated nitration of protein tyrosine residues, release copper and zinc ions, facilitate apoptosis of neurons and have enhanced peroxidase activity. Immunocytochemical studies demonstrated the presence of intense SOD1 immunoreactivity in Lewy body‐like inclusions, which are characteristic features of a certain form of familial ALS with posterior column involvement, in the lower motor neurons of patients in ALS families with different SOD1 mutations. More recently, strains of transgenic mice expressing mutant SOD1 have been established. These mice clinicopathologically develop a motor neuron disease mimicking human ALS with the exception of pronounced intraneuronal vacuolar degeneration. The overexpression of wild‐type SOD1 in mice has failed to give rise to the disease. Only one transgene for mutant SOD1 is enough to cause motor neuron degeneration and the severity of clinical course correlates with the transgene copy number. These observations in SOD1‐linked familial ALS and its transgenic mouse model suggest a novel neurotoxic function of mutant SOD1.
Molecular pathology of Alzheimer's disease
Authors: Yamazaki Tsuneo , Ihara Yasuo
Published: May 2007

Recent molecular and cellular approaches to the nature of Alzheimer's disease (AD) have revealed that the disease has a heterogenous genetic background. Thus, AD is not a disease but a syndrome. In the present article we review the significance of the causative and susceptibility genes of AD identified to date and discuss future perspectives of AD research.
Minigemistocytes and oligodendrocytic cells in mixed oligoastrocytomas: Immunohistochemical and Ultrastructural studies
Authors: Kamitani Hiroshi , Masuzawa Hideaki , Kanazawa Itaru , Kubo Toshiro
Published: May 2007

In five mixed oligoastrocytomas, minigemistocytes and fibrous astrocytes showed similar immunoreactions to glial fibrillary acidic protein (GFAP), vimentin (VM) and cytokeratin. Some oligodendrocytic cells also exhibited immunoreactivities to these intermediate filaments. Intercellular myelin basic protein immunoreactive products were not associated with any tumor cell. Four recurrent tumors exhibiting GFAP and VM immunoreactions were found to consist of anaplastic astrocytes and irregular round cells with scanty cytoplasm rather than typical oligodendrocytic cells and minigemistocytes. Ultrastructurally, the three types of tumor cells showed cytoplasmic organelles in common, appearing light in electron density and exhibiting few characteristics of mature or immature oligodendrocytes. The number of intermediate filaments was the only significant ultrastructural difference among them; moderate to many in fibrous astrocytes and minigemistocytes, a few to moderate in some oligodendrocytic cells, and few in other oligodendrocytic cells. Immunohistochemically and ultrastructurally, minigemistocytes, GFAP‐positive oligodendrocytic cells, and possibly GFAP‐negative oligodendrocytic cells appeared to belong to an astrocytic lineage rather than transitional cells between oligodendrocytes and astrocytes.
Studies on DNA fragmentation and disruption of the blood‐brain barrier in delayed radiation injuries in the rat brain
Authors: Toyonaga Shinichi , Mima Tatsuo , Kurisaka Masahiro , Mori Koreaki , Ogawa Yasuhiro
Published: May 2007

Delayed effect of radiation injury to the central nervous system often results in improper prognosis for the patients with malignant brain tumors. Two types of cell, the endothelial cell and the oligodendrocyte, are considered to be causative lesions for delayed radiation injury. Recently, morphological studies with both light and electron microscope have also indicated involvement of apoptosis at the acute stage of radiation injury. In the rat radiation injury model, we first examined the capillary endothelial cells when they were damaged after irradiation, using immunohistochemical analysis of endothelial blood antigen (EBA) as one of the indicators of normal function of the blood‐brain barrier (BBB). Secondly, we examined the types and location of DNA‐fragmented cells using in situ end‐labeling using the TUNEL (terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end labeling) method. A single dose of 10, 20 or 30 Gy was irradiated to the hemispheres and the brains were analyzed at 3, 6 and 12 months later. Although damage of endothelial cells was seen in the brains at 6 months after 20 Gy irradiation, disruption of BBB, as indicated by no immunoreactivity of EBA, occurred only in the brains at 12 months after 30 Gy irradiation. DNA fragmentation, indicated by TUNEL positive cells, were shown in the oligodendrocyte, astrocytes and endothelial cells in the brains at 6 months after 20 Gy irradiation. The results suggest that both disruption of BBB and apoptosis in the glial cells and endothelial cells are involved in the delayed radiation injury in the rat brain.
Ganglioside GD3 of cerebral neurons and Purkinje cells in aged human brains
Authors: Kawai Kensuke , Watarai Shinobu , Ishizu Ideki , Fukai Kosuke , Yasuda Tatsuji , Kuroda Shigetoshi
Published: May 2007

Immunocytochemical staining for ganglioside GD3 (II3α (NeuAcα2–8NeuAc)‐LacCer, GD3) in neuronal cells of the cerebral cortices (cerebral neurons), and cerebellar dentate nucleus (dentate neurons) and Purkinje cells, in human autopsy cases of progressive supranuclear palsy, senile dementia of the Alzheimer type, Pick's disease, amyotrophic lateral sclerosis and olivopontocerebellar atrophy (OPCA) was undertaken using mouse IgM anti‐GD3 monoclonal antibody. Cerebral neurons and dentate neurons were constantly GD3‐immunoreactive and immunoreactivity was observed in the cytoplasm. The peroxidase reaction product for GD3 (RP) in cerebral and dentate neurons was granular in appearance. It appeared that RP was associated with lipofuscin granules. However, immunoreactivity of Purkinje cells varied among cases, and the RP was slightly granular even when they were positive. This study suggests that lipofuscin granules contributed to the neuronal immunoreactivity of GD3 in aged human brains.
Immunohistochemical detection of anti‐oxidative stress enzymes in the dog brain
Authors: Kiatipattanasakul Wijit , Nakamura Shin‐ichiro , Kuroki Koji , Nakayama Hiroyuki , Doi Kunio
Published: May 2007

Anti‐oxidative stress enzymes were immunohistochemically detected in the brain from young to very‐aged dogs. More than half of the neurons in the cerebral cortex of the young dogs (< 5 years old) were positive for copper (Cu), zinc (Zn) superoxide dismutase (SOD), and the staining intensity was strong. The number of Cu, Zn SOD‐positive neurons decreased with age, and only 10–50% of neurons were positive for SOD in the aged and very aged (> 9 years old) dogs. In contrast, no glial cells were immunostained for Cu, Zn SOD in the young dogs, and the number, as well as the staining intensity, increased with age, reaching > 50% in the aged and very aged dogs. Apoptotic brain cells, which were conspicuous in the aged dog brain, were negative for Cu, Zn SOD. The Cu, Zn SOD immunoreactions were also observed in the degenerative neurites of amyloid type senile plaques, vessels affected with cerebral amyloid angiopathy (CAA) and reactive astroglia around these amyloid plaques and CAA in the aged and very aged dog brains. Diffuse type senile plaques were negative for Cu, Zn SOD. The number of catalase‐ or glutathione peroxidase‐positive cells varied among dogs regardless of their age. An age‐related decrease in number of Cu, Zn SOD‐positive neurons may enhance the toxicity of oxygen free radicals, resulting in neuronal cell death.
Rosenthal fibers and glial filaments associated with hemidesmosome‐like structures in perivascular astrocytes in a juvenile form of Alexander's disease
Authors: Iwaki Toru , Ogomori Koji , Tomokane Naoyuki , Kondo Akira , Tateishi Jun
Published: May 2007

We present a rare case of Alexander's disease occurring in a 10–year‐old girl with convulsive seizures. She initially developed gait disturbance and thereafter deteriorated mentally. At 48 years of age she died of cumulative convulsive seizures. The postmortem examination revealed a generalized and focally pronounced deposition of Rosenthal fibers in the deep cerebral white matter around the lateral ventricles. Atypical fibrillary glia, diffuse patchy demyelination and circumscribed cystic necrosis were also observed. An electron microscopic examination of the cerebral white matter revealed not only irregular, densely osmiophilic bodies merging in places with glial filaments, but also well‐developed hemidesmosomes associated with anchorage densities in the perivascular astrocytes. The subplasmalemmal anchorage densities usually received glial fibrils, which were frequently intermingled with Rosenthal fibers. Thus, our case can be added to the small number of previously reported cases demonstrating a juvenile form of Alexander's disease based on both clinicopathologic features and on ultrastructural appearance, and our case also confirms the profound involvement of astrocytes.
Diffuse neuroaxonal leukodystrophy with spheroids of adult onset: MRI and pathological studies
Authors: Hisanaga Kinya , Mochizuki Hiroshi , Konno Hidehiko , Saito Akihisa , Saito Jinichi , Kitahara Masakazu , Saito Hiroshi
Published: May 2007

A case of sudanophilic leukoencephalopathy of adult onset was reported. A 42‐year‐old Japanese woman showed progressive dementia, gait disturbance, apraxia of the left hand, left hemiparesis, and urinary and fecal incontinence. Magnetic resonance imaging (T2‐weighted scans and proton images) revealed a symmetrical widespread increase in the signal intensity of cerebral white matter, more prominent in the frontal lobes. Blood levels of very long chain fatty acids and arylsulfatase A were within normal limits. A needle biopsy specimen from the frontal lobe revealed severe demyelination with sudanophilic granules and neurofilament protein‐immunoreactive neuroaxonal spheroids in the white matter. The patient's mother was known to have similar symptoms and died at the age of 45, indicating an autosomal dominant inheritance. Because of the dominant inheritance, the psychiatric and neurological symptoms, and the characteristic neuroaxonal spheroids, the case was tentatively diagnosed as ‘hereditary diffuse leukoencephalopathy with spheroids’, a condition that has not been previously reported in Japan.
Amyotrophic lateral sclerosis with prolonged survival and degeneration of the spinocerebellar tracts, substantia nigra and dentatorubral system
Authors: Ono Seiitsu , Takahashi Keiichi , Fukuoka Yoshihiro , Jinnai Kenji , Kanda Fumio , Nagao Koichi
Published: May 2007

We report on a case of sporadic amyotrophic lateral sclerosis (ALS) with prolonged, respirator‐assisted survival and clinical signs limited to the upper and lower motor neuron systems. Autopsy revealed degeneration of the upper and lower neuron systems and Bunina bodies, both characteristic of ALS. In addition, we found degeneration of the spinocerebellar tracts, the substantia nigra and the dentatorubral system. Our case is an additional example of multisystem degeneration in ALS associated with prolonged, respirator‐assisted survival. These findings suggest that sporadic ALS comprises heterogeneous subgroups with patterns of degeneration that depend, in part, on survival time.
Sacral agenesis: A case report with pathogenetic consideration
Authors: Hori Akira
Published: May 2007

A boy, born to a diabetic mother, showed external as well as internal malformations, such as cleft palate, deformation of the lower extremities, absence of the left kidney and contralateral compensatory hypertrophy, hydronephron and hydroureter. He died due to sepsis at the age of 2_ months. At necropsy, the os sacrum was completely absent. The spinal canal was closed by osseous tissue at the level of the lowest lumbar vertebra. There was neither dorsal nor ventral dysraphism. The spinal cord segments were identifiable up to the L4/5 level and further spinal nerve roots formed the cauda equina. A duplication of the filum terminale was found that attached the cord to the bottom of the spinal canal. The caudal spinal cord was deformed, destructured and accompanied by astrocytic gliosis. The variety of the defect of lower spinal segments described in the literature (some cases included thoracic levels) and the existence of the filum terminale in our case suggest that the spinal cord anomaly in sacral agenesis is neither a primary partial neural tube agenesis during the embryonal canalization phase nor is it an ‘atrophy during ontogeny’ (due to the ‘no target‐no development principle’), but is rather a destruction or due to other extraneural causes. In this context, a role of maternal diabetes may etiopatho‐genetically be speculated.
Presenile non‐Alzheimer dementia with motor neuron disease and laminar spongiform degeneration
Authors: Mimura Masaru , Tominaga Itaru , Kashima Haruo , Honda Masao , Kosaka Kenji , Kato Yuji
Published: May 2007

We describe the clinicopathological findings in three autopsy cases of presenile dementia with motor neuron disease. These patients had a relatively rapid course involving dementia and muscle weakness with a distal pattern of atrophy in the upper extremities. Postmortem examination revealed features of motor neuron disease and spongiform cortical degeneration. The latter change was most marked in the second layer of the frontal or temporal cortex and included minimal to mild neuronal cell loss and mild to moderate gliosis. In this report we relate these patients' laminar spongiform degeneration to three other conditions; frontal lobe dementia, primary progressive aphasia and dementia lacking a distinctive histology. These three conditions and presenile dementia with motor neuron disease may fall within the spectrum of the non‐Alzheimer type frontotemporal degenerative dementia.
Distributional pattern of apoptotic cells in rat cerebellar vermis experimentally induced by methylmercury intoxication
Authors: Kobayashi Yoshiyasu , Sawa Hirofumi , Akagi Hirokatsu , Itakura Chitoshi , Fujioka Yasunori , Nagashima Kazuo
Published: May 2007

This report deals with the distributional pattern of apoptotic granule cells in rat cerebellar vermis following experimental methylmercury chloride (MMC) toxicosis. The rats administered MMC showed clinical signs of hind leg paralysis around day 19 and this developed to moribund by day 26. Pathologic examination of the moribund animals revealed that cerebellar degeneration characterized by apoptosis of the granule cells was not equally distributed in the cerebellar vermis; apoptotic granule cells were observed in the lingula, central lobule, Lobulus ascendens, pyramis vermis and culmen in the order of decreasing frequency. This selective vulnerability in MMC intoxication is similar to the granule cell loss of Minamata disease in humans and suggests that this rat model is a useful pathobiologic model for studying cerebellar degeneration in Minamata disease.
The fundamental architecture of the microvasculature of the basal ganglia and changes in senility
Authors: Nonaka Hiroko , Akima Michio , Nagayama Tadashi , Hatori Tsutomu , Zhang Z.
Published: May 2007

The microvascular architecture of the basal ganglia of human brains was studied on diaphanized specimens after intravascular barium injection and vascular stains. Observation by scanning electron microscope was also performed. The putamen and caudate nucieus showed dense capillary networks. Less dense capillary networks were noted in the capsula interna. The capillary network in the globus pallidus was less dense than that in the striatum but denser than that in the capsula interna. The lenticulostriate arteries ran through the putamen, across the internal capsule and reached the caudate nucleus. Though the arterial branches running within the putamen had many small branches, branching was minimal while crossing the capsula interna and began showing rich ramification again when they reached the caudate nucleus. There were retrograde ramifications in the putamen and caudate nucleus. They appeared to play a significant role in the regulation of blood pressure and are considered to play some role in the occurrence of circulatory disturbances which are prone to involve these structures. The fountain‐like ramifications were seen in the putamen and caudate nucleus, but their function is not clear. In the brains of senile patients, intertwining of the arterial blood vessels was noted in the fountain‐like rami. This structure began to appear in the patients over the age of 50. While the etiology of the intertwining of the arteries remains unknown, its increasing frequency with age supports a hypothesis that this represents a phenomenon correlated with aging or concomitant brain atrophy.
Pleomorphic xanthoastrocytoma: Ultrastructural study and origin of the tumor
Authors: Nakamura Saburo , Furuichi Makoto , Yoshida Kenshi
Published: May 2007

An origin for the tumor cells of a pleomorphic xanthoastrocytoma (PXA) in a 50‐year‐old female is proposed on the basis of electron microscopic findings. The tumor was located in the superficial supratentorial region. Cytoplasmic positivity for GFAP in both the spindle cells and most of the bizarre giant cells was revealed by immunostaining, indicating an astocytic origin of the tumor. The presence of relatively few organelles, abundant filaments and microtubules, as demonstrated by electron microscopy, also indicated characteristics of astrocytes. Ultrastructural examinations revealed the existence of basal laminas in the extracellular space surrounding the surface of the tumor cells and the presence of localized cytoplasmic densities associated with the plasma membrane adjacent to the basal lamina resembling hemidesmosomes. This suggests a close relationship between the basal lamina and astrocytes, such as that between astrocytes and the investing basal in the glia limitans. The structures strongly indicated a cell origin for PXA that was not from non‐specific astrocytes with secondary proliferation of meningeal fibroblasts, but from astrocytes in the glia limitans with investing basal lamina.
Variability of senile dementia of Alzheimer type: A clinicopathological viewpoint
Authors: Mitsuyama Yoshio
Published: May 2007

Senile dementia of Alzheimer type (SDAT) is a hetero‐genous entity and can be grouped into different categories based on clinicopathological characteristics. Although the presence of senile plaques, neurofibrillary tangles and neuronal loss throughout the cerebral cortices plays an important role in the development of SDAT, the presence of these structures is not essential. Sociopsychological factors should also be considered as important factors in the development of SDAT in subjects over 80 years of age.
Conditions of Alzheimer‐type dementia in the old‐old and oldest‐old patients with special reference to extreme conditions of brain aging
Authors: Mizutani Toshio , Nakamura Ken‐ichi , Enomoto Mutsuo , Sakata Masuhiro , Yamada Shigeo
Published: May 2007

A neuropathological study on 1540 consecutive autopsy brains ranging from 60 to 107 years of age revealed the following points. (1) Of the of the demented cases of the plaque‐predominant type, 93% were complicated with multiple tiny cortical infarcts. They showed a tendency for dementia to develop before or after the appearance or worsening of a systemic disorder such as cardiovascular disease, respiratory infection and cancer. However, there was no case showing Alzheimer‐type dementia (ATD). (2) The plaque‐predominant type might be an extreme condition of brain aging in terms of senile plaques (SP). It is likely that although the pathological appearance of SP alone is not responsible for dementia, its coexistence with multiple cortical infarcts could be the cause of dementia. Therefore, this type should be distinguished from ATD. (3) Primary hippocampal degeneration could also be an extreme condition of brain aging in terms of neurofibrillary tangles. This condition was different pathologically from the hippocampal lesion in ATD. (4) Several characteristics of old‐old and oldest‐old patients were clarified.
Neuroimaging findings in Alzheimer's disease
Authors: Fukuyama Hidenao
Published: May 2007

In the present article, the neuroimaging findings in Alzheimer's disease are summarized and experimental data from animals relating to metabolic changes in Alzheimer's disease (AD), particularly in the frontobasal cholinergic projections onto the cerebral cortex, are reviewed. Changes in glucose metabolism as well as in cerebral blood flow (CBF) are specific for AD, in which the parietotemporal association cortex shows metabolic suppression. This finding is used as a diagnostic aid in the clinical application of single photon emission computed tomography. In rare cases, limited suppression of metabolism and blood flow is also found in the unilateral medial temporal lobe or parietal lobe. Statistically, approximately 80% of cases of AD show a typical parietotemporal suppression pattern of CBF. This cortical metabolic and circulatory suppression has been attributed to cholinergic deprivation from the basal forebrain Mynert nucleus. Animal experiments have revealed transient cortical suppression of glucose metabolism in the frontal cortex after destruction of the basal forebrain cholinergic neurons by ibotenic acid. This suppression persists for approximately 1 week and returns to normal 1 month after operation. Thus, the typical neuroimaging findings in AD would not be due to deficient cholinergic projections from the basal forebrain.
Alzheimer's disease as a polygenic disease
Authors: Okuizumi Kaoru , Tsuji Shoji
Published: May 2007

Recent advances in molecular genetics have enabled the identification of the causative genes for early‐onset familial Alzheimer's disease (AD). However, sporadic and late‐onset familial AD, the most common forms of AD, are considered to be polygenic disorders. The presence of APOE4, one of the specific alleles of the apolipoprotein E gene, has been established as a major genetic risk factor for the development of AD. Additional risk factors are under active investigation. Such new approaches are expected to establish preventive measures or treatments for AD.
Molecular diagnosis of muscular dystrophies
Authors: Sugita Hideo
Published: May 2007

Dystrophin, the protein product of the DMD/BMD (Duchenne muscular dystrophy/Becker muscular dystrophy) gene, is associated with dystrophin‐associated proteins (DAPs), which are classified into three groups: the dystroglycan complex, the sarcoglycan complex and the syntrophin complex. There is a connecting axis between subsarcolemmal actin filaments and laminin, one of the main components of the extracellular matrix through dystrophin and dystroglycan. This system may play an important role in protecting the sarcolemma during contraction and relaxation of muscle fibers. In this paper, the abnormalities of DAPs and laminin as a cause of muscular dystrophies are reviewed. While there are no reports on the role of mutations of dystroglycan and the syntrophin gene as being a cause of muscular dystrophies, the immunostaining intensities of these complexes are reduced as a secondary phenomenon of defects of dystrophin in DMD. The sarcoglycan complex, which is comprised of membrane‐integrated proteins, contains at least four components, each of which is encoded by a separate gene. This complex plays a crucial role in the development of severe childhood autosomal recessive muscular dystrophy (SCARMD). In this disease, the absence of any single component may result in a loss of the complex function. Therefore, SCARMD develops irrespective of any mechanism involving a defect of individual genes. As such SCARMD is collectively referred to as sarcoglycanopathy. Laminin, a heterotrimer and genetic defect of the α2 subunit, has been shown to be the cause of the classical type of congenital muscular dystrophy. This disease is characterized by floppy infants with severe muscular dystrophy, dysmyelinating neuropathy and white matter changes in the brain. In the clinical setting and in the mouse model of this disease a defect of the laminin α2 subunit in skeletal muscle has been demonstrated. α2 subunit‐null mutant mice also exhibit the muscular dystrophy phenotype and a muscle pathology compatible with dystrophia muscularis (dy) mice. A final common mechanism of muscle‐cell necrosis in many of the muscular dystrophies is associated with the destabilization of the sarcolemma.
New‐variant Creutzfeldt‐Jakob disease
Authors: Ironside James W.
Published: May 2007

Surveillance of Creutzfeldt‐Jakob disease (CJD) was reinstituted in the United Kingdom in 1990 to monitor any effects of the bovine spongiform encephalopathy (BSE) agent on humans. In 1996, the CJD Surveillance Unit described a new variant of CJD, characterised by an unusually early age of onset, a prolonged clinical course with presenting features that were unusual for CJD, and a characteristic neuropathology. All patients were homozygous for methionine at codon 129 in the prion protein gene, with no mutations or insertions. At present, 23 patients have been diagnosed with this new disorder, but it is impossible at present to predict likely numbers of future cases. Strain typing studies in experimental mice have shown that the transmissible agent in new‐variant CJD has identical features to that of the BSE agent, but differs from that in sporadic CJD. The identification of disease‐associated prion protein in lymphoid tissue in newvariant CJD raises the possibility of lymphoid biopsy for early diagnosis, and indicates that the transmissible agent may be present in association with circulating lymphoid cells in the blood and other tissues. Although the mode of transmission of the BSE agent to humans is unknown, current evidence favours a dietary mode of spread. However, the precise route of spread, infectious dose and incubation period for BSE in humans are all unknown. Additional studies are required to provide further information, which will allow a more accurate understanding of disease pathogenesis and prediction of future disease trends.
Differential patterns of molecular genetic alterations define subsets among glioblastomas and oligoastrocytomas
Authors: von Deimling Andreas
Published: May 2007

Molecular genetic studies have uncovered a set of genes carrying somatic mutations in human brain tumors. While some molecular lesions are limited to distinct histopathological tumor types and grades, others exhibit a widespread distribution. This overlap and the limited number of identified genes currently restrict the feasibility of examining molecular lesions for diagnostic purposes. However, recent studies indicate that histopathological entities can be divided into molecular subsets based on characteristic and sometimes mutually exclusive genetic alterations. Among gliomas such genetic subsets have been described for glioblastomas and oligoastrocytomas. These observations should encourage researchers to include the examination of molecular parameters in study protocols for clinical and histopathological investigations.
A pilocytic astrocytoma from the roof of the third ventricle: An immunohistochemical and ultrastructural study
Authors: Kawano Hirokazu , Ikeda Tokuro , Yokogami Kiyotaka , Moriyama Takuzo , Goya Tomokazu , Wakisaka Shinichiro , Nabeshima Kazuki
Published: May 2007

A 6‐year‐old female with a rare third‐ventricle tumor is presented. On magnetic resonance imaging (MRI) the tumor appeared hypointense in T1‐weighted images and hyperintense in T2‐weighted images. Operative findings disclosed that the tumor arose from the roof of the third ventricle. Histological examination revealed a biphasic pattern and hyaline droplets in hematoxylin‐eosin (HE) staining, and glial fibrillary acidic protein (GFAP) and vimentin staining were both positive. Rich intermediate filaments and lysosomes were conspicuous in electron microscopic examination. This is a rare case of pilocytic astrocyioma arising from the roof of the third ventricle around the foramen of Monro.
Gene expression of C1q A‐chain in the rat facial nucleus after axotomy
Authors: Miyake Toshihiko , Gahara Yoshinari , Uwabe Ken‐Ichiro , Yamada Hajime , Kitamura Tadahisa
Published: May 2007

Differential hybridization screening of the cDNA libraries derived from the rat facial nucleus was performed, and a number of cDNA clones were isolated and found to be upregulated after facial nerve axotomy. One of the isolated cDNA clones encoded the A‐chain of C1q (C1q‐A) of the rat, whose cloning has not been reported in the literature. Sequence analysis showed that C1q‐A is well conserved in the rat, mouse and human on the DNA and protein levels. In situ hybridization demonstrated that there were strong signals for C1q‐A mRNA within the rat facial nucleus damaged by axotomy, and the signals were localized in activated microglia. Immunohistochemistry showed strong immunoreactivity for C1q protein in the activated microglia of the rat facial nucleus damaged by axotomy. C1q‐immunoreactivity was also found in the extracellular space of the damaged facial nucleus. No significant C1q‐A mRNA signals and C1q‐immunoreactivity were observed in the normal brain tissue. These results suggest that microglia markedly up‐regulate the C1q‐A gene to produce and secrete C1q in response to the neuronal damage caused by axotomy.