bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Time for Mating and Gestation Length on Reproductive Efficiency in Dogs
Authors: Shimatsu Y , Yuzawa H , Aruga K , Nakura M.
Published: October 2007

Contents

The purpose of this study was to examine the effect of time for mating and gestation length on reproductive efficiency in dogs. Groups of eight, six and six beagle bitches were mated with a total of three sires on days 3, 5 and 7, respectively, after the luteinizing hormone (LH) surge. All the bitches whelped successfully. The gestation lengths (the intervals from the LH surge to the whelping) were 65.1 ± 1.9, 65.5 ± 1.9 and 68.0 ± 1.8 days, respectively. This length of mating 7 days after the LH surge was significantly longer than that of mating 3 and 5 days after the LH surge (p < 0.05). The litter sizes were 5.5 ± 2.2, 6.2 ± 1.9 and 4.8 ± 2.1, respectively and there was no significant difference between any of the groups. In conclusion, mating 3–7 days after a bitch's LH surge results in a good reproductive efficiency and the intervals from the LH surge to the whelping of mating 7 days after the LH surge shows a longer day significantly in comparison with mating 3 and 5 days after the LH surge.
Bunina Bodies in Amyotrophic Lateral Sclerosis
Authors: Okamoto Koichi
Published: October 2007

Bunina bodies (BBs), small eosinophilic intraneuronal inclusions in the remaining lower motor neurons, are the only specific pathological hallmarks of amyotrophic lateral sclerosis (ALS). This report deals with the study of and provides a review on the morphology and morphogenesis of BBs. Immunohistochemical studies disclosed that BBs express cystatin C, but they failed to react with a variety of other antibodies. Serial electron microscopic investigations documented that BBs consisted of electron‐dense amorphous material that contains tubular and vesicular structures and that in the early stages of BB formation the amorphous material was sometimes present around the tubular and vesicular structures. From immunoelectron microscopic studies with the antiserum to cystatin C, there was evidence for the presence of immunoperoxidase reaction products in the periphery of BBs. Furthermore, cystatin C was mainly localized in the Golgi apparatus of anterior horn cells of an adult cat. It would appear that BBs may represent abnormal accumulations of unknown proteinaceous materials that are associated with the Golgi apparatus.
Hyaline and Skein‐like Inclusions in Amyotrophic Lateral Sclerosis
Authors: Mizusawa Hidehiro
Published: October 2007

Hyaline (HI) and skein‐like inclusions (SLI) are characteristic of familial and sporadic amyotrophic lateral sclerosis (ALS). The HIs are usually round eosinophilic structures, some of which consist of cores and halos and are called Lewy body‐like HIs. The HIs, composed of various amounts of granule‐associated thick filaments and neurofilaments, have varied appearances and may be heterogeneous. The SLI is basically a thready structure of a bundle of thick filaments. The threads may be present singly or in the form of networks or aggregates with each other. Occasionally, aggregates of threads may form single larger inclusions that resemble HIs. These features indicate that the HI and the SLI may be closely related. Other than their intense ubiquitination, the molecular nature of HI and SLI is still unknown. The investigation of the genesis of these inclusions may provide important clues for elucidating the pathomechanism of ALS.
Non‐motor Neuron System in Amyotrophic Lateral Sclerosis: Involvement of Clarke's Column and Intermediolateral Nucleus
Authors: Takahashi Hitoshi , Oyanagi Kiyomitsu , Ikuta Fusahiro
Published: October 2007

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects the motor neuron system. However dose only the motor neuron system degenerate selectively in this disease? On the basis of histologic and morphometric studies on Clarke's column and intermediolateral nucleus (IML) neurons, which belong to the non‐motor neuron system in the spinal cord, we report in this Symposium presentation that in sporadic ALS, they are also primarily involved in the disease process. However, the rate of degeneration of these neurons is much slower than that of lower motor neurons. Our results indicate that Clarke's column neurons and IML neurons in the lower thoracic segments may start to disappear after the patients have begun to require respiratory support, which is the final stage of the natural hintory of the disease. In addition, it should also be empasized that Bunina bodies and spheroids are neuropathological features of Clarke's column in ALS patients, but not of the IML.
Neuropathology in Amyotrophic Lateral Sclerosis Patients on Respirators: Uniformity and Diversity in 13 Cases
Authors: Kato Shuichi , Oda Masaya , Hayashi Hideaki
Published: October 2007

We performed a neuropathological study on 13 patients with amyotrophic lateral sclerosis (ALS) who had been on respirator support. Twelve patients had developed upper and lower motor neuron signs, exclusively, before being placed on respirators. One patient was diagnosed as having the pseudoneuritic type of ALS. The main pathological findings in the 13 cases were the simultaneous involvement of both motor neurons and the presence of Bunina bodies and ubiquitinated filaments in the anterior horn cells. While on the respirator, two rapidly progressing patients developed supranuclear ophthalmoplegia and ended in totally locked‐in state. These two cases showed widespread systemic degenerative changes in the central nervous system (CNS) that involved the frontoparietal cortices adjacent to the precentral gryrus, the pallido‐luysio‐nigral system, thalamus, hypothalamus, amygdala, brain stem tegmentum, dentate‐rubral system, Clarke's spinocerebellar‐middle root zone and Onuf's nucleus. Eight normally or rapidly progressing patients developed supranuclear ophthalmoplegia, with or without emotional disinhibition and blood pressure lability. Some of the CNS structures affected in the two patients described above, were also altered in these eight cases. We attribute the ophthalmoplegia to the involvement of the brain stem tegmentum and frontal cortices, which are concerned with eye movement. In addition, the emotional and autonomic labilities of some of the patients may be related to alterations of the limbic system. By contrast, the clinicopathological features of the remaining three, slowly progressing patients were confined to both motor neurons. On the basis of these findings we address the intrinsic uniformity of ALS and some of its diversities
Clinicopathological Study of Two Respirator‐assisted Long Survival Cases of Amyotrophic Lateral Sclerosis
Authors: Hashizume Yoshio , Yoshida Mari , Murakami Nobuyuki
Published: October 2007

This report concerns the evaluation of the clinicopathological features of amyotrophic lateral sclerosis (ALS) in two male patients who survived ten years with the assistance of artificial respirators. The patients were 54 and 52 years old at disease onset and they were placed on respirators 32 and 27 months later, respectively. The patients did not show impairments in occulomotor, sensory and rectovesical functions nor develop bedsores, with the tetrad of ALS being negative. The main histopathological changes observed include neuron loss of the upper and lower motor systems and degeneration of the pyramidal tract. By contrast, other systems such as the posterior column, spinocerebellar tracts, Clarke's nucleus, oculomotor nucleus and Onuf's nucleus remained intact. These findings on our two patients suggests that there may be cases in which the selective features of ALS are maintained throughout prolonged respiratory management.
Myopathy, Unique Clinical Features, and Brain Malformations Mimicking Fukuyama Congenital Muscular Dystrophy: A Case Report
Authors: Nakayama Hiroshi , Ando Susumu , Tomi Hideaki , Sunohara Nobuhiko , Nonaka Ikuya , Eto Komyo , Satoyoshi Eijiro
Published: October 2007

The pathological findings of an adult woman and clinical features of her brothers identified a new type of congenital muscular dystrophy with brain malformation. The 40‐year‐old woman, born to parents who were first cousins, was retarded in both mental and physical development from early infancy. She had a monkey‐like face with macroglossia, dwarfism, decreased subcutaneous fat with hard skin, joint contracture, and muscular atrophy and weakness with myopathic changes, but she was able to walk until the age of 31 years. Two brothers showed clinical features more or less similar to hers, but their mental and physical development was not severely retarded. Autopsy of the patient revealed that the brain malformation consisted of micropolygyria and pachygyria, and the muscular atrophy was of the normal dystrophin type. In addition, presenile occurrence of Alzheimer's neurofibrillary tangles was prominent in the malformed brain. The overall picture was that of congenital muscular dystrophy of the Fukuyama type, demonstrating an adult variant of the disease.
Three Cases with Cavitary Lesions in a Twin Gestation Complicated by a Single Intrauterine Fetal Demise
Authors: Tamagawa Kimiko , Ishibashi Ryoko , Mizuno Yoshihiko , Komiya Kazuhiko , Oda Masaya , Shinozaki Masako , Kurata Kiyoko , Satoh Junichi , Morimatsu Yoshio
Published: October 2007

Three cases with cavitary lesions on the cerebral convexities in twin gestation complicated by a single intrauterine fetal demise were investigated clinicopathologically. They all exhibited profound mental retardation and severe motor disturbance due to rigidospastic tetraplegia. The co‐twins were macerated.

Neuropathologically, malformed lesions and destructive lesions coexisted in varying degrees according to the time in fetal life, at which insults probably occurred. The cavitary lesions were located bilaterally and symmetrically on the central, parietal and occipital region of the cerebral hemispheres, in some cases, including the frontal region. Case 1 showed an incomplete gyral pattern and porencephaly with polymicrogyria bordering the defect, thus allowing us to date the insult before the 5th fetal month. In case 2, multicystic encephalomalacia was disclosed with cortical dysgenesis exhibiting status marmoratus of the cortex. Case 3 displayed sclerotic cavitary lesions with sclerosis of the insula and a few instances of cortical dysgenesis. Based on the clinical data and pathological findings, the cavitary lesions of case3 may be dated in the third trimester of gestation. Case 2 can be considered to have sustained injuries between the times estimated for cases 1 and 3.

As the pathogenesis of the congenital cavitary lesions, several concepts have been proposed: intrauterine DIC (Moore et al. 1969;Romero et al. 1984), vascular disruption (Hoyme et al. 1981;Jung et al. 1984), intrauterine infection such as cytomegalic inclusion disease (Friede et al. 1976), and hypoxia due to CO intoxication of the mother (Bank1 et al. 1967) or other cause. Though the pathological observation of our cases revealed no evidence of intrauterine DIC, renal cortic necrosis, intrauterine infection or occlusion of the intracranial

vessels, long‐term exposure to the dead twin might have contributed to the lesions of the liveborn co‐twin.
Immunohistochemical Study on Glial Cells in Brains with Periventricular Leukomalacia
Authors: Iida Kouichi , Takashima Sachio
Published: October 2007

The lesions in periventricular leukomalacia (PVL) comprise necrosis and a glial reaction in the deep cerebral white matter of fetuses and neonates. The purpose of this study was to elucidate the role of glial cells in the formation of the lesions in PVL. Ten PVL brains and 22 control brains were immunohistochemically compared using anti‐glial fibrillary acidic protein (GFAP) and anti‐ferritin antibodies, and lectin‐Ricinus communis agglutinin (RCA‐1).

The numbers of GFAP‐positive glia and RCA‐1 positive glia increased in the whole white matter and the periventricular white matter, respectively. Ferritin was predominantly stained in the cytoplasm of oligodendrocytes, and the number of ferritin‐positive oligodendrocytes gradually increased with age in normal brains. However, ferritin was stained in microglia and partially reactive astrocytes, instead of ferritin‐positive oligodendrocytes, in PVL brains.

A relationship of the glial cellular reaction with the time scale of histologic change in PVL was shown by the appearance of RCA‐1‐positive microglia around fresh necrotic regions, accumulation of RCA‐1‐positive macrophages in necrotic regions, and then proliferation of GFAP‐positive reactive astrocytes with long processes outside the microglial reaction sites. On cavity formation, the end‐stage of PVL, rough walls of moderately dense gliosis consisted of slightly GFAP‐positive fibrillary astrocytes.

PVL involves glial cellular reactions not only in regional necrotic lesions, but also in the whole cerebral white matter. The decrease in ferritin‐positive oligodendrocytes in PVL brains may be related to the delayed myelination in the brains of long‐surviving infants with PVL.
Morphological Developmental Delay in the Brain in Down Syndrome
Authors: Mito Takashi , Takashima Sachio , Becker Laurence E.
Published: October 2007

Neuropathological abnormalities in Down syndrome are reviewed and reported. Among these are subtle but characteristic alterations in brain growth and development most apparent after 1 year of age. Neurons are also altered in Down syndrome. There are reductions in total dendritic length and number of spines begining at around 4 months of age. In addition, the number of the S‐100 protein positive cells is increased in the perinatal period correlating perhaps with increased expression in Down syndrome because of the presence of three chromosome 21s. Down syndrome is a complete disorder which can only be analyzed by utilizing a wide variety of techniques.
Pathophysiology of Down Syndrome: Consideration from Clinical Neurology
Authors: Segawa Masaya
Published: October 2007

Down syndrome (DS) is a representative disorder of mental retardation caused by chromosomal aberration. However, its pathophysiologies have remained unclarified, though its neuropathological similarity to Alzheimer disease is attended. There have been few reports of precise neurological examination of this syndrome for detecting the loci of the lesion. In this report, we present the results of neurlogical and clinical neurophysiological studies on patients with DS and suggest the involvement of serotonergic (5HTergic) neurons as the main pathophysiology of this syndrome.
Immunohistochemical Investigations on Cerebellar Purkinje Cells of Menkes' Kinky Hair Disease: Disappearance of Inositol 1, 4, 5‐Triphosphate Receptor Protein, and Expression of Phosphorylated Neurofilament Proteins, αB‐Crystallin and Stress‐response Proteins
Authors: Kato Shinsuke , Ito Masayuki , Ohama Eisaku , Mikoshiba Katsuhiko , Maeda Nobuaki , Hirano Asao
Published: October 2007

Immunohistochemical investigations were carried out on cerebellar Purkinje cells in patients with Menkes' kinky hair disease (MD) and normal control subjects (ages: 1–65 years). Six antibodies were used. They were specific to inositol 1,4,5‐triphosphate receptor protein regarded as P400 (P400/IP3R), phosphorylated neurofilament proteins (pNFP), αB‐crystallin, stress‐response protein (srp) 72, srp 27 and ubiquitin, respectively. In normal brains, all Purkinje cell bodies, axons, and dendrites including the spiny branchlets of dendrites were positive for anti‐P400/IP3R antibody. In comparison, not every Purkinje cells in MD cases had P400/IP3R immunoreactivity. And some of the cells were more intensely stained than others. The immunoreaction products of P400/IP3R were frequently detected in cell bodies and proximal portions of the dendrites, but not in the peripheral dendrites including spiny branchlets. Most of the Purkinje cell bodies in MD reacted with anti‐pNFP antibody, while only a small fraction of the cells was positive with anti‐αB‐crystallin and srp 72 and srp 27. Ubiquitin immunoreactivity was not detected. In contrast, Purkinje cell bodies from normal subjects were not recognized by antibody to pNFP, αB‐crystallin, srp 72 and srp 27. Our results indicate that MD is associated with the loss of inositol 1,4,5‐triphosphate receptor in Purkinje cells, and an aberrant phosphorylation of neurofilament proteins or aberrant distribution of normal phosphorylated neurofilament proteins. These impairments may lead to the expression of stress response proteins or αB‐crystallin in some cells.
The Macular Mutant Mouse as a Model of Menkes' Kinky Hair Disease and Pathology on Its Cerebellar Purkinje Cell
Authors: Yamano Tsunekazu , Xu Gui‐Qin , Shimada Morimi
Published: October 2007

The macular mutant mouse is well known as a model of Menkes kinky hair disease (MKHD). This paper was presented to elucidate the pathogenesis of cerebellar Purkinje cell abnormalities of MKHD using this model mouse. The neuropathological changes on the Purkinje cells of this mouse were composed of somal sprout, somal spine, focal dendritic swelling, delay of arborization, abnormal mitochondria, abnormal inclusions, and low cytochrome c oxidase activity. Most of them were improved in the hemizygote treated with cupric chloride. These abnormal Purkinje cells were not distributed in a mosaic pattern in the cerebellum of the heterozygote. Hence, most of them resulted from copper deficiency in the cerebellum, and not from gene abnormality in the Purkinje cell.
Acute Encephalopathy with Necrosis of Bilateral Thalami: Clinical Aspects
Authors: Mizuguchi Masashi
Published: October 2007

An unusual type of acute encephalopathy is prevalent among Japanese children. The disorder is characterized by the bilateral symmetrical, edematous and necrotic brain lesions. Clinical and pathological evidence indicates that the encephalopathy is a novel entity. Its pathomechanism remains to be solved.
Early Occurrence of Alzheimer's Neurofibrillary Tangles (NFT) in Developmental Brain Damage and Chronic Brain Diseases with Early Childhood Onset
Authors: Takada Kuniyasu
Published: October 2007

We observed early occurrence of neurofibrillary tangles (NFT) in brains with various types of developmental brain damage or chronic neurologic disorders starting at infancy or early childhood. The diseases included Fukuyama congenital muscular dystrophy (FCMD), porencephaly, postencephalitic epilepsy, hydrocephalus, Cockayne's syndrome and Hallervorden‐Spatz disease. The earliest NFT were observed in a 12‐year‐old girl with congenital toxoplasmosis, but most of the patients were over 20 years of age. NFT frequently occurred in the cerebral cortex, nucleus basalis of Meynert and brain stem nuclei, but were not common in the hippocampus. Senile plaques were absent in all cases. We discuss the significance and hypothesis of NFT occurrence in such patients.
Alteration of Astrocytes in Non‐Gliotic Lesions after Protracted Non‐Missile Head Injury
Authors: Arai Nobutaka , Morimatsu Yoshio , Mizutani Toshio
Published: October 2007

Morphological and immunohistochemical observations of a pathologic from of astrocytes, called “clasmatodendritic astrocytes (CAs)”, are described for descrived for two cases of protracted non‐missile head injury. CAs were moderately swollen and characterized by disintegration of their processes which were clearly demonstrated by Cajal staining of the astrocytes. In both cases, CAs appeared not in astrogliotic scar lesions but in non‐astrogliotic rarefied white matter lesions. Immunohistochemically, almost all CAs reacted weakly with glial fibrillary acidic protein. Also, a number of CAs (approximately 75%) strongly reacted with laminin and alphal‐antichymotrypsin. These observations provide suggestive evidence that CAs do not produce fibrillary astrogliosis, which is considered to interfere with neurite regeneration, but play other roles after brain injuries. The possible altered nature of CAs is discussed.
ALS in the Kii Peninsula of Japan, with Special Reference to Neurofibrillary Tangles and Aluminum
Authors: Kihira Tameko , Yoshida Sohei , Mitani Kazuo , Yasui Masayuki , Yase Yoshiro
Published: October 2007

Epidemiological and environmental findings of the foci of amyotrophi lateral sclerosis (ALS) in the Western Pacific indicate a possible contributing role of metals, especially aluminum, in the pathogenesis. Al is also a candidate as a causative agent in the formation of neurofibrillary tangles (NFTs), which are characteristic of Guam ALS. To elucidate the pathogenesis of ALS, we conducted neuropathological examination and metal analysis, with special reference to NFT and Al in cases of ALS in the Kii Peninsula of Japan. We examined six of these ALS cases, ten ALS cases from non‐focused areas (non‐focused ALS) and eight disease controls.

The neuropathologic characteristics of Kii ALS were the appearance of NFT in Ammon's horn, temporal cortex, mid‐brain and pons, in ccombination with typical ALS pathology. No senile plaque was found in the Kii cases. Non‐foused ALS patients rarely showed NFTs in Ammon's horn.

Al analysis of Ammon's horns by particle‐induced X‐ray emission spectrometry (PIXE) revealed a high level of Al signals in the Kii cases, with positive correlation between Al content and NFT frequency. Kii ALS cases showed high level of Al signals in the cervical and lumbar spinal cords ccompared with non‐foused ALS and controls. The Morin fluorescent technique revealed more conspicuous green fluorescence in the cytoplasm and nuclei of both the NFT‐laden neurons and the degenerative neurons without NFT in Ammon's horn in the Kii ALS cases than in non‐focused ALS cases. Green fluorescence was seen in a small number (2%) of the NFTs themselves.

We suggest that Al induces abnormality in cytoskeletal protein such as neurofilaments and/or tau, and may cause the formation of NFT in Ammon's horn and also degeneration of motor neurons in Kii ALS.
Evaluation of Neuropathological Stages Based on Quantification of Senile Changes in Non‐Demented Elderly Individuals and Alzheimer‐Type Dementia
Authors: Iseki Eizo , Odawara Toshinari , Kosaka Kenji , Haga Chie , Ikeda Kenji
Published: October 2007

Amyloid deposits (AmD) and neurofibrillary tangles (NFT) were quantitatively examined in methenamine‐silver stained hemisphere sections from 98 non‐demented elderly individuals and 30 patients with Alzheimer‐type dementia (ATD). Of the non‐demented cases, 35 (35.7%) had some AmD, and 72 (73.5%) had some NFT, whereas all the ATD cases had both AmD and NFT. AmD‐and NFT‐positive cases were classified into developmental stages, based on the distribution and incidence of each of these senile changes (AmD: A1, A2, B1, B2, C′ and C; NFT: Ia, Ib, IIa, IIb, III, and IV). When the AmD‐positive cases were divided into stages A‐B and stages C′‐C and the NFT‐positive cases into stages I‐III and stage IV, all the non‐demented individuals were found to belong to NFT stages I‐III and all the ATD cases to AmD stages C′‐C. This study provides evidence that an approximate dividing line can be drawn between non‐demented individuals and ATD patients by using quantitative neuropathological criteria, and that the distinction between the two groups can usually be made on the basis of the difference in the incidence of AmD in the precentral motor area and the incidence of NFT in the temporal isocortex.
Immunohistochemical Studies on Cerebellar Purkinje Cells of Patients with Menkes' Kinky Hair Disease
Authors: Kato Shinsuke , Ito Masayuki , Ohama Eisaku , Mikoshiba Katsuhiko , Maeda Nobuaki , Yen Shu‐Hui , Hirano Asao , Herz Fritz , Shintaku Masayuki
Published: October 2007

Immunohistochemical investigations were carried out on cerebellar Purkinje cells of eight patients with Menkes' kinky hair disease (MD) using an antibody against the inositol 1, 4, 5‐triphosphate receptor which is identical to the cerebellar Purkinje cell glycoprotein P400 (P400/IP3R). In normal cerebellar Purkinje cells, the cell bodies, axons and dendrites including spiny branchlets were specifically stained by the antibody. By comparison, the immunoreactivity of the MD Purkinje cells ranged from negative to positive. The most frequent staining pattern in the MD Purkinje cells was that of cell bodies and proximal portions of the dendrites expressing P400/IP3R in varying degrees, with the peripheral dendrites including spiny branchlets not being stained. The Purkinje cells of the eight patients were also analyzed for expression of phosphorylated neurofilament proteins (pNFP), αB‐crystallin, stress‐response protein (srp) 72, srp 27 and ubiquitin. Most MD Purkinje cell bodies reacted with the antibody against pNFP. Although the proportion of stained Purkinje cells was less, a positive reaction was also observed with the antibodies to αB‐crystallin, srp 72 and srp 27. By contrast, no normal Purkinje cell was stained by these antibodies. Our results suggest that the function of P400/IP3R in the Purkinje cells of MD patients is impaired, that these cells have an aberrant phosphorylation of NFP and that some of the imparied Purkinje cells synthesize specific sets of stress‐related proteins.
Neuropathological Study of the Amygdaloid Subnuclei in Senile Dementia of the Alzheimer Type, with Special Reference to the Basolateral Subnuclei
Authors: Mukai Masami , Mizutani Toshio , Yamada Shigeo
Published: October 2007

This systematic study concerns the comparison of amygdaloid changes in 16 patients with senile dementia of the Alzheimer type (SDAT) and 16 control subjects. While previous studies have dealt mainly with the distribution of senile plaques (SPs) and neurofibrillary tangles (NFTs), we focused on the degree and distribution of both, neuronal loss and astrocytosis in the amygdala. Our results indicate that brain atrophy was restricted to the medial temporal gyri of most cases, with the anterior portion of the temporal lobes being preferentially involved. With respect to the amygdala, the most pronounced degeneration was in the basolateral subnuclei, i.e., accessory basal, basal, and lateral nuclei. We found that the degree of astrocytosis exceeded that of neuronal loss by far, and that the accessory basal nucleus exhibited the most severe alterations. There was marked neuronal loss with astrocytosis in the cerebral cortex, entorhinal cortex and prosubiculum, and there appears to exist a correlation of the degree of neuronal loss in the amygdala with that in the entorhinal cortex and prosubiculum. By contrast, the presence of SPs and NFTs in the amygdala did not correlate with the extent of neuronal loss, but numerous SPs and NFTs were seen in the corticomedial subnuclei of the SDAT patients. However, the striking loss of neurons and the pronounced astrocytosis in the basolateral subnuclei merit emphasis, since these abnormalities could be responsible for the atrophy of the amygdala.
Non‐Wilson's Type Neurological Disorder Associated with Abnormal Copper Metabolism. The First Autopsy Case Report
Authors: Shintaku Masayuki , Kojima Yasuhiro , Suzuki Satoshi , Kato Tomonobu
Published: October 2007

This report concerns an autopsy case of a peculiar neurodegenerative disorder associated with abnormal copper metabolism. The patient was a 46‐year‐old woman, who presented with dementia and ataxia, and who died after a progressive clinical course of approximately 19 months. The patient had marked hypocupremia and hypoceruloplasminemia. The neuropathological examination revealed: (1) neuronal loss with remarkable rarefaction of the neuropil of the mammillary body; (2) severe thalamic degeneration; (3) degeneration and softening of the olivary nucleus, accompanied by remarkable capillary proliferation; (4) coarse spongy state or vacuolization of the cerebral white matter, and (5) degeneration of Clarke's column. The cerebral cortex, basal ganglia, and cerebellar cortex were preserved; brain deposition of iron and copper was not detected. The liver showed congestion, parenchymal atrophy and iron deposition, but neither copper deposition nor cirrhotic changes. Although the clinical features of patients with neurological disorders associated with abnormal copper metabolism, but distinct from both Wilson's disease and Menkes' kinky hair disease have been described, no autopsy case report has been published to date. It is of particular interest that the subnuclear distribution pattern of the thalamic lesion and the isolated degeneration of Clarke's column and the posterior spinocerebellar tract of the spinal cord of the present patient closely resembled the lesions in Menkes' kinky hair disease.
Incidence and Distribution of Senile Plaques and Neurofibrillary Tangles in Late‐onset Diffuse Lewy Body Disease
Authors: Odawara Toshinari , Iseki Eizo , Kosaka Kenji , Haga Chie , Ikeda Kenji
Published: October 2007

This report presents the results of a quantitative investigation on incidence and distribution of senile plaques (SPs) and neurofibrillary tangles (NFTs) in ten cases of late‐onset diffuse Lewy body disease (DLBD). The methenamine‐silver method was used. SP were distributed throughout the cerebral cortices of all cases. The SP stages in seven of them were compatible with those of Alzheimer‐type dementia (ATD). NFTs occurred most frequently in the transentorhinal and entorhinal pre α regions and the hippocampal CA‐1 area. The occurrence of NFTs was generally restricted to the hippocampus and parahippocampal cortex. NFTs were rarely encountered in the neocortex. The NFT stages of all ten cases were compatible with those borderline between ATD and physiological aging. When both, the SP and NFT stages are considered concurrently, the majority of our late‐onset DLBD cases had levels that corresponded to those in the very mild of ATD or the borderline between ATD and physiological aging. The occurrence of certain DLBD cases with senile changes that are insufficient for a diagnosis of ATD indicates that DLBD should not be regarded as representing part of an ATD spectrum.
Gracile Axonal Dystrophy in an Old (28 Years) Japanese Monkey: Species‐Specificity of Ultrastructural Features and Particular Pattern of Proliferation of Smooth Endoplasmic Reticulum
Authors: Fujisawa Kohshiro
Published: October 2007

This report deals with the study of aging gracile axonal dystrophy in an old (28 years), but healthy Japanese monkey. Light and electron microscopy was used throughout. The animal was systemically perfused, under deep anesthesia, with a mixture of glutaraldehyde and paraformaldehyde. For light microscopy, epoxy resin‐embedded tissue of the gracile nucleus was cut into one μm sections, and for electron microscopy (accelerating voltage 300 KV), into 0.2 μm sections. The fine structure of over 20 different spheroids was investigated. Several ultrastructural features not previously observed and/or documented in lower mammals were found in the spheroids of the monky studied. These features are: 1) a unique pattern of smooth endoplasmic reticulum proliferation, characterized by dense parallel alignment of non‐branching tubules; 2) the accumulation of dense homogeneous osmiophilic substance; 3) presence of screw‐like paracrystalline needles, and 4) absence of such characteristic secondary structures as layered loops of membranes and coiled tubular rings. The dense homogeneous osmiophilic substance and the screw‐like paracrystalline needles were previously described or claimed to be present in aging axonal dystrophy of humans. The author addresses and emphasizes the value and importance of a comparative approach in neuropathology and concludes that the study of the brains of other primates is indispensable for the elucidation of human axonal dystrophy, brain aging in humans, and human brain diseases in general.
Ultrastructural Relationship between Lewy Bodies and Pale Bodies Studied in Locus Ceruleus Neurons of a Non‐Parkinsonian Patient
Authors: Takahashi Hitoshi , Iwanaga Keisuke , Egawa Shigekimi , Ikuta Fusahiro
Published: October 2007

The Lewy body (LB) is a hallmark of Parkinson's disease (PD). The pale body (PB) also represents a characteristic intracytoplasmic alteration of the neurons of the substantia nigra and locus ceruleus of PD patients. We recently had the opportunity to study a non‐parkinsonian patient (a 66‐year‐old man) who had numerous LBs and PBs in the neurons of the locus ceruleus. However, there was no evidence of neuronal loss in this region. We performed a detailed ultrastructural study of these inclusions for which multiple serial sections were used. Our results revealed that the constituent filamentous structures of the LBs and PBs were indistinguishable from each other, that transitions occasionally occurred between PBs and LBs, and that presynaptic structures entrapped in the cytoplasm were frequently present in the vicinity of both types of inclusion bodies. These findings suggest that PBs, at least those of the present type, actually represent early LBs. In addition, the entrapment of presynaptic structures by the cytoplasm of neurons of the locus ceruleus may indicate the existence of certain degenerative (or regressive) processes in these cells and that postsynaptic areas in particular, may have a role in PB and LB formation.
Neuronal Degeneration in the Brain of Brindled Mice: Combined Histochemical and Biochemical Studies on Cytochrome Oxidase and Superoxide Dismutase Activities
Authors: Yoshimura Noriaki , Hatayama Ichiro , Sato Kiyomi , Kida Kazuyuki , Usutani Saburo
Published: October 2007

In an effort to elucidate the mechanism(s) responsible for the brain degeneration in Menkes' disease, the authors determined the activities of two copper‐containing enzymes, cytochrome oxidase and superoxide dismutase in brains of brindled hemizygous mice (BM) before and after the injection of 10 mUg/g of cupric chloride (CuCI2) on postnatal day 7. Combined use was made of histochemical and biochemical methods. Histochemical staining for brain cytochrome oxidase in untreated BM was greatly decreased, and by biochemical analysis found to be approximately 30% of the normal level. By contrast, the activity levels in BM surviving for 6 to 12 months following the injection were the same as those in the normal control animals. Similar results were obtained for superoxide dismutase. Sequential chronological assays revealed that brain cytochrome oxidase activity of copper (Cu)‐treated BM gradually increased as a function of age, reaching normal levels by the end of 25 weeks. These findings were in concordance with the normal morphological features of the animals. However, the brain Cu content of the Cu‐treated BM showed only a slight increase; normal concentrations were not reached even by 26 months post‐treatment, when their Cu levels were 55.4% those of the normal controls. Taken together, these results may explain the mechanism of brain degeneration and efficacy of Cu therapy in Menkes' disease, and may offer hope for treating this inherited disorder. However, before it can be put into practice, it would be important to devise effective means for the safe delivery of Cu to an affected human fetus before it sustains irreversible brain damage.
Slowly Progressive Amnesia without Dementia
Authors: Tanabe Hirotaka , Kazui Hiroaki , Ikeda Manabu , Hashikawa Kazuo , Hashimoto Mamoru , Yamada Norifumi , Eguchi Yoko
Published: October 2007

This report concerns longitudin's investigations with comprehensive neuropsychologic's assessments and precise morphologic's, CT and MRI scan‐based, and function's, SPECT scan‐based brain imaging examinations of seven patients who had selective progressive amnesia on their initi's visit. Progressive loss of recent memory remained for sever's years the single most s'sient feature in six of them. The atrophy of the hippocamp's region was observed morphologic'sly, and dysfunction confined to the bilater's medi's tempor's lobe involving the hippocamp's area was demonstrated function'sly. These findings are consistent with recently reported atypic's cases of 'Szheimer's disease with unique neur‐opathologic's changes, namely the presence of numerous neurofibrillary tangles and few plaques in the hippocamp's region only.
Demonstration of neuropil thread‐like structures in the spinal cord white matter in progressive supranuclear palsy: An immunohistochemical investigation
Authors: Umahara Takahiko , Hirano Asao , Kato Shinsuke , Shibata Noriyuki , Yen Shu‐Hui C.
Published: October 2007

The presentation and distribution of neurofibrillary tangles (NFT), neuropil thread‐like structures (T‐LS) and smaller structures (dots) in the spinal cord of two patients with progressive supranuclear palsy (PSP) is discussed. Monoclonal antibodies to Alzheimer neurofibrillary tangles (ANT) and tau protein were used. Immunoreactive NFT were detected in the spinal cord gray matter. The number of tau‐positive NFT was significantly smaller than that of NFT stained by the anti‐ANT antibody. However, T‐LS and dots immunolabeled by the latter were detected in the gray and white matter. Most white matter T‐LS and immunoreactive dots were found in the anterior funiculus. These findings provide immunohistochemical evidence for the presence of these abnormal structures in the spinal cord white matter of patients with PSP.
The occurrence of corpus amylaceum (polyglucosan body) in diabetes mellitus
Authors: Leel‐Ossy L.
Published: October 2007

Numbers of corpora amylacea (CA) were observed among 1407 autopsied and/or biopsied cases where diabetes mellitus had been diagnosed clinically and in those where the diabetes mellitus did not exist. A comparative examination was carried out by a semi‐quantitative method which revealed a significant difference in the incidence of CA between 100 diabetic and 100 non‐diabetic cases. However, there was not a significant difference in the incidence of CA between the diabetic and ischemic cases who have also shown a tendency for developing CA. The results were evaluated statistically by homogeneity examination. Diabetes may enhance the tendency for forming CA by the hyperglycemia increasing the quantity of unused carbohydrate polymers, which are the main components of CA. Changes in the metabolism of glucose by astrocytes caused by aging or by some pathological processes may play a primary role in the developing of CA. Other factors such as the greater volume of cerebrospinal fluid, barrier disturbances and pathological changes which are associated with the appearance of heat stroke protein positivity in CA, also have a prominent role in this type of astrocytic degeneration. The presence of CA does not have any pathognostic significance but some conditions favor its development. A theory is also suggested for the formation of CA similar to other types of biocrystalloids in the central nervous system.
A pathological study of Lewy bodies and senile changes in the amygdala in diffuse Lewy body disease
Authors: Iseki Eizo , Odawara Toshinari , Suzuki Kyoko , Kosaka Kenji , Akiyama Haruhiko , Ikeda Kenji
Published: October 2007

A quantitative study of the distribution and incidence of Lewy bodies (LB) and senile changes was performed in seven subnuclei of the amygdala in 12 cases with diffuse Lewy body disease (DLBD). The results were compared with those in six cases of idiopathic Parkinson's disease (PD), six cases of Alzheimer‐type dementia (ATD) and six cases of non‐demented controls. Ubiquitin immunohisto‐chemistry for LB, methenamine‐silver stain for senile plaques (SP) and Gallyas stain for neurofibrillary tangles (NFT) were used in this study. In all DLBD cases and four PD cases, cortical LB occurred in all subnuclei with a tendency for their preferential occurrence in certain sub‐nuclei. The probable dysfunction in these subnuclei may contribute to the memory impairment of DLBD. Senile plaques and NFT occurred significantly more frequently in the baso‐lateral nuclear group than in the cortico‐medial nuclear group of the amygdala in DLBD cases as well as in ATD cases, although a tendency for these to occur predominantly in certain subnuclei was not observed. In the central amygdaloid nucleus (CE), many characteristic spherical or fusiform structures were stained positively with ubiquitin immunohistochemistry in all DLBD and PD cases, although the number was less in PD cases. These immunohistochemically ubiquitin positive structures were densely packed electronmicroscopically with ubiquitin‐positive granular and vesicular components. They might have arisen from selective degeneration of the terminal or distal axons of noradrenergic and dopaminergic afferents from the locus ceruleus and substantia nigra, respectively, to the CE.
Progressive myoclonus epilepsy with unusual neuropathologic features
Authors: Mizukami Katsuyoshi , Sasaki Megumi , Imai Kohbun , Hori Takafumi , Shiraishi Hiroyasu , Haraoka Seiji , Watanabe Teruo , Kosaka Kenji , Goto Yu‐ichi
Published: October 2007

An autopsy case of progressive myoclonic epilepsy (PME) with unusual neuropathologic features is discussed. The patient was a 46 year old man who presented with prominent cerebellar ataxia and an intention tremor, in addition to myoclonic movements and grand mal seizures. He was clinically diagnosed as having PME, in particular dys‐synergia cerebellaris myoclonica (DCM; Ramsay Hunt syndrome). A neuropathologic examination revealed severe degeneration of the cerebellar cortex, mild nerve cell loss with marked fibrillary gliosis of the dentate nucleus, and focal laminar necrosis and mild diffuse nerve cell loss in the frontal cortex. Other recent clinicopathologic studies have revealed that most patients with Ramsay Hunt syndrome are diagnosed pathologically as having either mitochondrial encephalomyopathy, especially myoclonus epilepsy with ragged red fiber (MERRF), or dentatorubral or dentatorubropallidoluysian atrophy (DRPLA). The present case is thought to be unusual in that no pathologic features of MERRF or DRPLA were demonstrated.
Pleomorphic xanthoastrocytoma: New ultrastructural observations
Authors: Takahashi Hitoshi , Kakita Akiyoshi , Honda Yoshiho , Kameyama Shigeki , Tanaka Ryuichi , Ikuta Fusahiro
Published: October 2007

A 58 year old woman presented with a right frontal lobe cystic mass diagnosed as pleomorphic xanthoastrocytoma (PXA), in which a reticulin fiber network was not evident but prominent vasculature was noted (angiomatous variant). The patient had a 36 year history of epileptic seizure which had been relatively well controlled with anticonvulsants. An ultrastructural study revealed that the neoplastic astrocytes occasionally contained filamentous inclusions identical to Hirano bodies in their cytoplasm and that, at the periphery of the tumor, pre‐existing axon terminals and synaptic junctions were found in close proximity to neoplastic astrocytes. The former may represent a degenerative process in the constituent neoplastic astrocytes and the latter appears to be of interest when considering the epileptogenic lesions associated with this type of benign tumor.
Dentatorubropallidoluysian atrophy: Further development of human neuropathology
Authors: Mizutani Toshio
Published: October 2007

The discovery of the abnormalities of CAG codon repeats in dentatorubropallidoluysian atrophy (DRPLA) by gene analysis has had a strong impact on human neuropathology. Some believe that the new method can show all aspects of this disease. This paper highlights many gaps which exist between the genotype and the phenotype, and consider that human Neuropathology could fill these gaps. It is emphasized that pathogenetical investigation, which is needed to link gene abnormalities, has been inadequate to date. It is also stressed that a clinico‐anatomical approach is still necessary for progress in pathogenetical research and human neuro‐anatomy.
White matter damage in dentatorubropallidoluysian atrophy: A radiological and neuropathological study
Authors: Arai Kimihito
Published: October 2007

Dentatorubropallidoluysian atrophy (DRPLA) is a spinocerebellar degeneration. Diffuse high signal areas in T2‐weighted magnetic resonance imaging (MRI) are frequently observed in the cerebral white matter in DRPLA, but the pathological details have never been documented. The computerized tomographic (CT) scan findings of three DRPLA cases are detailed, with emphasis on changes over time and their white matter pathology. The three cases were aged 59,46 and 46 and the duration of illness ranged from 7 to 18 years. All cases showed abnormal signal echo in the cerebral white matter and represented severe dementia. The CT scans revealed the low density areas in white matter. They were diffuse and some had an uneven and flecked appearance. The extent and degree of the low density areas had progressed over time. The CT scan findings in case 1 changed at the period when a rapid worsening of dementia was seen. A common pathological feature of cerebral white matter was a decrease in myelin sheaths and oligodendrocytes. The reaction of astrocytes and macrophages was slight and there was no fibrillary gliosis. The small vessels showed edematous necrosis. These findings suggest the disturbance of microcirculation in deeper areas of the white matter. White matter damage in DRPLA shows another pathological process different from the system degeneration.
Cytopathology of amyotrophic lateral sclerosis: A personal perspective of recent developments
Authors: Hirano Asao
Published: October 2007

Amyotrophic lateral sclerosis (ALS) is an age‐associated neurodegenerative disease that primarily involves the motor neuron system. Despite this disease having been studied for over 100 years, its etiology is still unknown and no specific diagnostic laboratory test is available. The diagnosis of ALS is therefore based on clinical and/or neuropathological findings with loss and degeneration of the large anterior horn cells of the spinal cord being the principal and most salient features. Several symposia and workshops on the cytopathology of ALS were held within the last 2 year period, which reflects the many new and important developments taking place. Although loss of motor neurons has been well‐known for many years, cytoplasmic alterations of the lower motor neurons have been studied in detail only in recent years by applying immunohistochemical and electron microscopic procedures. The purpose of this review is to introduce some of the novel findings associated with lower motor neuron alterations.
An immunohistochemical study of Alzheimer neurofibrillary tangles using confocal laser scan microscopy
Authors: Ohwada Jiro , Nishiyama Etsuko , Iwamoto Norihiko , Arai Heii
Published: October 2007

Double immunofluorescent stainings of neurofibrillary tangles (NFT) were performed using anti‐tau, ubiquitin, amyloid P component and neurofilament antibodies. A confocal laser scan microscope was used to investigate the distribution and the relationship of these components. Tau‐ and ubiquitin‐immunoreactivities (IR) were observed in the same NFT. Tau‐ and neurofilament‐IR were observed in the same neuron. Tau‐ and amyloid P com‐ponent‐IR were not colocalized in the same NFT. These findings may suggest a process of NFT‐formation which will help in the understanding of pathophysiology of Alzheimer's disease.