bluuebunny/crossref_metadata_2025 huggingface dataset:
Tubular profile of the Gallyas‐ and tau‐positive argyrophilic threads in corticobasal degeneration: An electronmicroscopic study
Authors: Arima Kunimasa
Published: October 2007

Two brains with corticobasal degeneration (CBD) were examined in order to elucidate the immunocytochemical and ultrastructural characteristics of argyrophilic threads (AT) and oligodendroglial cytoskeletal alterations. Gallyaspositive oligodendroglial perikaryal coiled bodies reacted positively with antibodies against tau and ubiquitin immunohistochemically, and consisted of 15 to 20 nm tubules with occasional irregular constrictions ultrastructurally. The present study demonstrated, for the first time, that (i) the tubular structure of the non‐physiological nature actually aggregated in the inner and outer loops of the myelin sheath, which corresponded to the histological AT; (ii) these tubules were 15 to 20 nm in diameter with occasional irregular constrictions ultrastructurally, coated with silver particles in Gallyas electronmicroscopy, positive for anti‐tau, and weakly positive for anti‐ubiquitin antibodies immunocytochemically; and (iii) the plasma membrane of the inner and outer loops that surrounded these abnormal tubules of AT was immunolabeled by both anti‐tau and anti‐ubiquitin antibodies. Argyrophilic threads and oligodendroglial perikaryal coiled bodies share the immunohistochemical, immunocytochemical, and electronmicroscopical characteristics. Therefore, it is considered that the common tau‐pathology may develop in the oligodendroglia from the perikarya throughout its process. In conclusion, the cytoskeletal pathology in oligodendroglial process is of significance in the pathoetiology of CBD.
Argyrophililic/tau‐positive glial inclusions in parkinsonism‐dementia complex of Guam
Authors: Oyanagi Kiyomitsu , Ikuta Fusahiro
Published: October 2007

Tau‐immunopositive and Gallyas preparation‐positive inclusions were observed in the oligodendroglial and astrocytic cells, in addition to extensive neurofibrillary tangles (NFT) in the brains of Guam parkinsonism‐dementia complex (Guam PDC) patients who had been autopsied from 1979 to 1982. Crescent‐ or coil‐shaped intracytoplasmic inclusions were observed in the oligodendroglial cells, predominantly in the medial nucleus of the thalamus, motor cortex, globus pallidus, pyramis of the medulla oblongata and lateral funiculus of the spinal cord. Granular hazy cytoplasmic inclusions were observed in the astrocytic cells many in the amygdaloid nucleus, in the inferior olivary nucleus, and in the lateral funiculus in the cervical segment of the spinal cord. These granular hazy inclusions have ever been reported and the distribution pattern of the crescentkoiled inclusions in Guam PDC is different from that reported previously in other NFT‐ or argyrophilic grain‐forming diseases. These findings indicate that Guam PDC involves not only neurons but also oligodendroglial and astrocytic cells. The morphological differences from the other NFT‐forming diseases may provide further insight into the distinct etiopathogenesis of Guam PDC.
Dementia of the Alzheimer type and related dementias in the aged: DAT subgroups and senile dementia of the neurofibrillary tangle type
Authors: Yamada Masahito , Itoh Yoshinori , Otomo Eiichi , Suematsu Naomi , Matsushita Masaaki
Published: October 2007

The aims of this study are to elucidate variations in the neuropathology of dementia of the Alzheimer's type (DAT) and related dementias in the elderly, and to delineate a senile dementia characterized by abundant neurofibrillary tangles (NFT) in the hippocampal region and by a scarcity of senile plaques (SP) throghout the brain (senile dementia of the NFT type; SD‐NFT) in comparison with usual DAT cases. One hundred and five autopsied patients who developed dementia at age 70–100 years were investigated. The autopsy series included 57 cases of DAT, five of diffuse Lewy body disease (DLBD) with Alzheimer‐tyupe neuropathological changes, and five of SD‐NFT. The 57 DAT patients were classified into three subgroups depending onthe severity of the neocotical neuronal degeneration (NFT and neuronal loss): the diffuse, severe type (DAT‐DS, extensive and severe involvement of the neocortex; n= 18); the diffuse, mild type (DAT‐DM, mild involvement of the neocortex; n= 29); and the localized type (DAT‐L, neuronal degeneration almost localized to the hippocampal region; DAT without neocortical NFT; n= 10). The frequencies of the DAT subgroups, DLBD, and SD‐NFT in each age group at the onset were DAT‐DS (41%) > DAT‐DM (38%) > DLBD (16%) > DAT‐L (6%) of patients in their 70s, DAT‐DM (52%) > DAT‐L (24%) > DAT‐DS (16%) > SD‐NFT (8%) of those in their 80s, and DAT‐DS (40%) > SD‐NFT (30%) > DAT‐L (20%) > DAT‐DS (10%) of those in their 90s and older. In a morphometric comparison with age‐mathced DAT cases, the SD‐NFT showed a significantly higher density of hippocampal NFT and a significant scarcity of SP and cerebral amyloid angiopathy in the brain. Analysis of genotypes of apolipoprotein E gene revealed that no patient with the SD‐NFT had ε4 allele which was shown to be frequently associated with DAT. Our results have indicated (i) that the later onset of DAT and related dementias is linked with the milder neuronal degeneration in the neocortex, and (ii) that the SD‐NFT is a common neuropathological condition that causes dementia in the very aged, in which the pathogenetic process may be different from that in DAT.
Pathologic processes leading to cerebral hemorrhage in amyloid angiopathy
Authors: Takashashi Reisuk Heavy , Sawa Hirofumi , Kuroda Satoshi , Saito Hisatoshi , Fujita Miri , Fujioka Yasunori , Fukatsu Ryo , Nagashima Kazuo
Published: October 2007

This report concerns a study undertaken to eluidate the pathogenesis of arterial rupture related to amyloid deposition. For this purpose, histochemical and immunohistochemical analyses were carried out on brain tissue specimens of a case of cerebral amyloid angiopathy (CAA) with multiple cortical hemorrhages. A small amount of amyloid β‐protein was found in the tunica media vasorum in which the smooth muscle cells were well preserved. with increases in amyloiod deposition, the entire arteriolar wall became concenmtrically thick, with amyloid largely occupying the tunica media; the number of smooth muscle cells was decreased and these cells were located in the intimal side of the vessel wall. Under these conditions, the elastic fibers and endothhelial cells were relatively well preserved. In the advanced stage of amyloid deposition, the arterioles became devoid of smooth muscle cells and underwent wither fibrous luminal occlusionor aneurysmal dilatation with fibrinoid necrosis and loss of elastic fibers; the latterwould eventually rupture causing the hemorrhage. These findings suggest that amyloid β‐protein‐related loss of arteriolar smooth muscle cells could be the initial event, with the subsequent damage of the vascular wall leading to cerebral hemorrhages in CAA patients.
Electron micrograph of ubiquitin‐positive intraneuronal inclusions in the extra‐motor cortices in patients with amyotrophic lateral sclerosis
Authors: Okamoto Koichi , Hirai Shunsaku , Amari Masakuni , Sakurai Atsushi
Published: October 2007

The ultrastructure of ubiquitin‐positive intraneuronal inclusions in extra‐motor cortices was examined in two patients with amyotrophic lateral sclerosis associated with dementia (ALS‐D) using paired routine electron microscopic ultrathin sections and adjacent 1 μm thick semithin sections. The ubiquitin‐positive structures consisted mainly of granules associated with a few filaments of approximately 15 nm in diameter. The granules seemed to consist of altered ribosomes, namely they were less electron dense and more irregular and had more amorphous outlines than did the ribosomes in non‐ubiquitinated cytoplasms. Our findings suggest the development of ribosome‐associated and ubiquitin‐related abnnormalities in the neurons of the extra‐motor cortices of ALS‐D patients.
Pathogenesis of delayed radiation injury in the rat spinal cord after X‐ray irradiation
Authors: Miyagawa Hidehito , Yokofujita Junko , Okeda Riki , Kuroiwa Toshihiko
Published: October 2007

The pathogenesis of delayed radiation injury was examined experimentally. Exposure fields in the thoracic and lumbar spinal cords of 54 adult female specific pathogen‐free Wistar rats were X‐ray irradiated. The rats were observed clinically and pathologically for up to 6 months after irradiation and the relationships between the chronological progress of paralysis and pathological findings and between vascular and parenchymal changes were analyzed by reconstructing serial spinal cord sections.
Abnormal glial cytoskeleton in progressive supranuclear palsy
Authors: Amano Naoji , Takahashi Tatsuya , Yagishita Saburo , Inoue Masayuki , Matsushita Masaaki
Published: October 2007

Progressive supranuclear palsy (PSP) is characterized by neurodegenerative changes of the basal ganglia, brainstem and the cerebellum. Moreover, it is noteworthy that abnormal cytoskeleton of glial cells is distributed widely in the brain. The morphological, immunohistochemical and ultrastructural properties of the properties of the peculiar glia have been elucidated. However, many factors remain unsettled regarding the abnormalities. The purpose of this paper is to define the properties of PSP, to present its distributional characteristics, and to examine the correlation of PSP with neuronal loss and astrocytosis.
Oligodendroglial microtubular tangles in multiple system atrophy
Authors: Nakazato Yoichi , Suzuki Sinobu
Published: October 2007

Oligodendroglial microtubular tangles (OMT) were observed in the central nervous system in 10 cases of multiple system atrophy (MSA) including eight cases of sporadic olivopontocerebellar atrophy and one case of Shy‐Drager syndrome and one of striatonigral degeneration. There was no OMT in two cases of hereditary spinocerebellar degeneration, nor in 46 cases with various neurological and non‐neurological diseases. The distribution of OMT was correlated with the location of neurodegenerative changes due to MSA, and the number of OMT with the severity of those changes. Immunoreactivity with anti‐ubiquitin and α B‐crystallin antibodies was observed by immunohistochemical procedures. It is suggested that the OMT is a pathognomonic change of MSA and confirms the validity of the concept of MSA as a disease entity.
Clinicopathological study on multiple spongy necrosis of the pontine base
Authors: Ujihira Nobuko , Hashizume Yoshio
Published: October 2007

Eleven cases with multiple spongy necrosis of the pontine base are reported and their clinicopathologic characteristics discussed. Seven of the cases occurred in men and four in women; age ranged from 42 to 90 years old. Eight patients had various types of cancer as background disease. Three patients received central nervous system (CNS) radiotherapy and six received chemotherapy. No consistent clinical factor (e.g., malignancy, radiotherapy, chemotherapy, severe immunosuppressive state, specific laboratory data and infection) could be found among the cases. Neuropathological findings were characterized as multiple patchy spongy areas of the pontine base with loss of myelin and axons. There were few reactive gliosis or inflammatory changes. Many axonal swellings and a small number of macrophages were scattered in the lesions. Neurons and glial cells adjacent to these lesions were not affected, and calcification was not found. Almost all of the lesions existed in the transverse fibers of the basis pontis. In the literature, malignancy or toxicity due to CNS radiotherapy or chemotherapy was suspected to be the causative factor of these lesions. In our 11 cases, however, the lesions were also found in patients who had not received radiotherapy or chemotherapy. In contrast, the neuropathological findings of the lesions in our patients were similar in each case. Electronmicroscopically, the myelin sheath was seen to be swollen in the early stage of the lesion. Excluding malignancy, radiotherapy and chemotherapy, there may be an additional unknown causative factor. Metabolic disturbances or toxic agents for myelin were suspected as causative factors.
Cerebral germinoma with marked granulomatous inflammation: Granulomatous germinoma
Authors: Gotoda Hiroko , Fujita Miri , Inoue Kazuaki , Nagashima Kazuo , Sawamura Yutaka , Tada Mitsuhiro , Abe Hiroshi , Oka Koji , Yanagida Noritake , Nanjo Hiroshi
Published: October 2007

Cerebral germinomas with granulomatous inflammation are rare lesions that can present diagnostic difficulties. Four cases (two male and two female) of germinomas with pronounced inflammatory reaction are presented. The age ranged from 14 to 21 years (mean 18). Three patients with vision defects had masses around the sellar region, and a long duration of symptoms (2, 4 and 5 years). The fourth patient had a mass in the temporal lobe; she had convulsions and the duration of her symptoms was short (3 weeks). All lesions consisted of inflammatory changes with scattered neoplastic germinoma cells that expressed placental alkaline phosphatase. The inflammation area occupied more than two‐thirds of the mass, and consisted of macrophages and their syncytial forms of mutinucleated giant cells, T‐cells, B‐cells, plasma cells, fibroblasts, and histiocytes or glial cells. Sarcoid granulomata were frequently seen, and multinucleated giant cells with Schaumann's bodies were also visible. The term ‘cerebral granulomatous germinoma’ is proposed for these unusual tumors. Moreover, it is likely that the study of cerebral granulomatous germinoma may provide some important clues towards the understanding of granulomatous inflammation in organs in general.
Degeneration of the synaptic boutons of parallel fibers in rats treated with methylmercury: Chronological observations
Authors: Su Mu , Kakita Akiyoshi , Yamada Mitsunori , Takahashi Hitoshi , Ikuta Fusahiro
Published: October 2007

We investigated the changes in the cerebellar cortex of adult rats after oral administration of 10mg/kg per day methylmercury (MeHg) for 10 consecutive days. Using a light microscope, darkly stained granule cells were shown to first appear on day 4 after the final dose, and increased in number thereafter. On day 11, many granule cells became degenerated, whereas the Purkinje cells were well preserved. Ultrastructural investigation revealed swelling of the parallel fiber synaptic boutons (the axonal terminals of granule cells), as early as on day 2, although the cell bodies and parallel fibers showed no obvious change. From day 8, in addition to the swollen boutons, many electron‐dense boutons were observed. The dendritic spines of the Purkinje cells (i.e. the postsynaptic structures of parallel fibers), showed no obvious change at any stage. Immunohistochemistry for synaptic vesicle‐specific protein (SVP) demonstrated a decrease of granular labeling in the molecular layer from day 8 onwards. Immunohistochemical expression of inositol 1,4,5‐trisphosphate 3‐kinase (IP3K), which is known to be associated with the spine, was constant throughout. It is considered that the SVP and IP3K profiles correspond well to the ultrastructural features of the pre‐and postsynaptic structures, respectively. In conclusion, this study shows that MeHg intoxication of the granule cells in adult rats initially induces morphological change in the synaptic boutons, the degeneration of which does not involve the dendritic spines of the Purkinje cells transneuronally at least for the survival observed.
Dissociative brain stem lesions in cephalothoracopagus twins
Authors: Hayashi Masaharu , Kojima Hideaki , Morimatsu Yoshio , Shinohara Takeshi , Fujioka Yasunori , Nagashima Kazuo
Published: October 2007

This report concerns unusual central nervous system (CNS) abnormalities in female cephalothoracopagus twins delivered after 29 weeks of pregnancy, and who died soon after birth. The two bodies, fused to a single umbilical cord, had one head and face, and four arms and four legs. Thorax, lungs, heart, esophagus and stomach were shared by both. In the CNS, there was one cerebrum with two separate pontes, cerebella, medulla oblongatae and spinal cords, which were set at 60d̀ to each other. The diencephalon was shared by the twins. In each brain stem, the nuclei of motor trigeminal, abducent, facial and hypoglossal nerves were rudimentary on the conjoined sides, but the neurons in other nuclei such as the locus ceruleus, pontine nucleus, superior and inferior olivary nuclei, and the area postrema were preserved bilaterally. The pyramidal tract in the brain stem and spinal cord was affected only on the conjoined side. These brain anomalies provide valuable information for investigations dealing with CNS development.
Fukuyama congenital muscular dystrophy: Cortical dysplasia of the cerebrum in a 20 week fetus
Authors: Yamamoto Tomoko , Komori Takashi , Shibata Noriyuki , Kondo Eri , Saito Kayoko , Osawa Makiko , Toda Tatsushi
Published: October 2007

This report describes cerebral cortical dysplasia in a 20 week fetus, aborted as a result of the prenatal genetic analysis which provided evidence of Fukuyama congenital muscular dystrophy (FCMD). The histological appearance of the brain of this fetus was similar to that of previously described cases. However, cortical dysplasia was less severe in this 20 week fetus, and the interesting finding was the existence of a leptomeningeal lesion probably preceding dysplasia. In this case, abnormal findings were found mainly in the cerebral surface, and maturation of the brain seemed appropriate for the gestational age. Furthermore, periodic acid‐methenamine‐silver‐positive linear structure of the cerebral surface was disrupted irregularly. These findings suggest that defects in the pial‐glial barrier of the cerebral surface may play a cardinal role for the genesis of cortical dysplasia. It is suggested that the extracortical abnormal tissue would be detectable morphologically at least in the 12‐13th week because cells considered as subpial granular cells were contained in the lesion. This report on the brain of a fetus with FCMD provides information on relatively early central nervous system alterations in this disease, and may be of importance in clarifying their pathogenesis.
Bunina body‐like eosinophilic intracytoplasmic inlusions in a gangliocytomatous brain lesion
Authors: Takahashi Hitoshi , Egawa Sigekimi , Ikuta Fusahiro
Published: October 2007

Small, round eosinophilic intracytoplasmic inclusions jin the constituent neuronal cells of a gangliocytomatous nodule found in a temporal lobe glioneuronal lesion of a 17‐year‐old boy with intractable complex ipartial seizures is described. These inclusions, measuring several micrometers in diameter, were often multiple in the neuronal cells, forming clusters with a bead‐ or ribbon‐like appearance. Characteristically, they often showed clear areas within them. An ultrastuctural study using selected light microscopic sections revealed that they were electron dense, granular structures with or without fingerprints‐like multilamellar profiles, and often contained a number of translucent inner areas. These inclusions with and without fingerprint‐like multilamellar profiles appeared to be similar to the previously described multilamellar inclusions and Bunina bodies, respectively. The present finding is of great interest when considering that Bunina bodies are a pathological hallmark of amlyotrophic lateral sclerosis (ALS) and that in some patients with ALS, the concurrence of multilamellar inclusions and Bunina bodies in the same neurons has been described.
Astroglial reaction pattern in human immunodeficiency virus type 1 infected brains
Authors: Itoh Kyoko , Mehraein Parviz , Weis Serge
Published: October 2007

The reaction pattern of astrocytes was investigated by means of immunohistochemistry and morphometry in 36 brain regions of human immunodeficiency virus type 1 infected patients and of normal controls. The numerical density of astrocytes immunoreactive for glial fibrillary acidic protein (GFAP) was determined. In HIV1 infected brains, the number of GFAP‐positive astrocytes was significantly increased in all investigated brain regions as compared with normal controls. The increase in number of GFAP‐positive, reactive astrocytes might play a crucial role in triggering pathogenetic mechanisms leading to cell damage and death in HIV1 infected brains.
A Morphometric study of subcortical neurofibrillary tangles in Alzheimer's disease
Authors: Ohara Kazuyuki , Takauchi Shigeru , Miyoshi Koho , Kokai Masahiro , Morita Yoshio
Published: October 2007

The numbers of neurofibrillary tangles(NFT) in the subcortical nuclei detected in Gallyas‐Nissl double stained sections was evaluated with computer‐based image analysis techniques. This was undertaken to examine the susceptibility to NFT formation and to identify mutual correlations in NFT formation among the basal ganglia in Alzheimer's disease (AD). The numbers of NFT are insufficient to compare the regional differences of NFT in each nucleus of the AD brains because large subcortical gray nuclei tend to have more NFT, Incidences of NFT were given definitions in order to find the NFT incidences for the expected neuronal populations, The definitions used were: the ratio of total numbers of NFT observed in a given subcortical gray nucleus of AD brains to the total numbers of medium‐ to large‐sized neurons(≥ 150μm2) in which the nucleoli were confirmed in the corresponding structure of control brains. A common order of susceptibility to NFT changes was found among the subcortical nuclei in advanced stages of AD cases, According to NFT incidences, subcortical nuclei were classified into four groups. The highest incidence of NFT (88%) was found in the nucleus basalis of Meynert. The severely affected group (NFT Incidences; 28–44%) included the raphe nucleus (superior central nucleus), anterior thalamic nucleus (anterior ventral thalamic nucleus), locus ceruleus and claustrum, The putamen, substantia nigra (zona compacta), medial thalamic nucleus (medio‐dorsal thalamic nucleus) and lateral thalamic nucleus (ventro‐lateral and ventro‐anterior thalamic nuclei) comprised the moderately affected group (NFT incidences; 9–15%). The substantia nigra (zona reticulata), globus pallidus, subthalamic nucleus and red nucleus constituted the slightly affected group (NFT incidences;<5%). In spite of the group classifications, no significant mutual correlations in NFT incidences between any pair of subcortical nuclei were indicated. The present study suggests that the NFT formations in AD take place in the subcortical nuclei according to individual susceptibility, irrespective of the connections between the nuclei.
Microscopic morphometry of the spinal cord with cervical spondylotic myelopathy
Authors: Zhang Chen , Goto Noboru , Suzuki Masataka , Zhou Ming
Published: October 2007

Quantitative studies with morphometric assessments were carried out on the slpinal cord of four cases (aged 71–88 years) with cervical spondylotic myelopathy (CSM), and compared with four normal spinal cords from age‐matched cadaver specimens (aged 76–84 years). The histological preparation of the slpinal cord was made after embedding in celloidin and staining with luxol fast blue‐periodic acid‐Schiff‐hematoxylin and Klüver‐Barrera methods. the number, average transverse area and perimeter of the anterior horn cells (AHC) in the Rexed's lamina IX at C3, C5, C6 and L1 levels were counted and measured; the number, average transverse area and perimeter of axon in the posterior funiculus at C3 level and in the lateral corticospinal tracts at L1 level were also counted and measured under high magnification with oil immersion (1340 times), using a combination of an electronic optical planimeter, a microscope with a drawing tube, and a personal computer. The results can be summarized as: (i) The numbers of AHC in CSM at C5, C6 and L1 levels were significantly decreased compared with normal controls, and the average transverse area of AHC at C6 and L1 levels showed a decrease in varying degrees (p<0.05 or P<0.01, respectively). However, the number and average area of AHC in CSM at C3 level did not show any difference. (ii) The number and average transverse area of axons in the posterior funiculus with CSM at C3 level showed a significant reduction compared with normal controls (P<0.01 and P<0.05, respectively). (iii) There was an obvious decrease in the number of axons in the lateral corticospinal tracts of CSM at L1 level (P<0.01), but the average area of axons showed no statistical reduction. It can be deduced from these results that there were ascending degeneration of the posterior funciculus and descending degeneration of the lateral corticospinal tracts above and below the segments of comparession caused by CSM. The loss in number and reduction in transverse area of AHC mainly occurred in those segments involved with compression. However, the result of AHC at L1 level revealed that CSM may have a distal influence on AHC below thesegments of compression.
Clinical aspects of progressive supranuclear palsy
Authors: Amano Naoji , Takahashi Tatsuya
Published: October 2007

Thirteen cases histologically proven as progressive supranuclear palsy (PSP) and 16 clinical cases were evaluated to help understand the clinical spectrum of symptoms, signs and clinical courses, and for differential diagnosis of corticobasal degeneration, Pick's disease and other neurodegenerative diseases. There was no case that was correctly diagnosed at the onset of the illness. Although the clinical courses and symptoms were uniform and typical of ordinary cases, fundamental symptoms such as ophthalmoplegia and nuchal dystonia were not observed in all cases. Some cases revealed a periodic stuporous state, and there was no symptom suggesting cerebral cortical lesions in any of the 29 cases. The clinical characteristics of PSP are discussed, with reference made to recent literatures.
Clinical features of corticobasal degeneration
Authors: Ueno Eriko
Published: October 2007

Coritcobasal degeneratin (CBD) has various neurological findings, such as cortical sign, parkinsonism, supranuclear palsy, myoclonus, and dementia. This disease used to be rare, but 20 years later, many case have been reported. Corticobasal degeneration is investigated from a wide range of specific analyses. It presents with a clinical resemblance to progressive supranuclear palsy (PSP) and it is important to determine whether CBD and PSP are the same entity. I will attempt to review the difference and similarities between PSP and CBD from a clinical standpoint.
Neuropathology of progressive supranuclear palsy
Authors: Inoue Masayuki , Yagishita Saburo , Amano Naoji , Takahashi Tatsuya , Hanihara Tokiji
Published: October 2007

The fundamental neuropathological findings of progressive supranuclear palsy (PSP) are presented, based on 14 autopsied cases of PSP. The blunt pathologies of PSP are degeneration in the substantia nigra, globus pallidus, subthalamic nuclei, dentate nucleus of the cerebellum and red nucleus, where there are neuronal loss, gliosis and neurofibrillary changes, to varying degree. In addition, the atrophy of the midbrain, especially the characteristic pattern of tegmental atrophy of the pons exhibiting a hand‐bag profile, is an important finding. Hypertrophy of inferior olivary nucleus is frequently observed, suggesting the existence of lesions in the dentato‐olivary system. Hypoxemic affects at the agonal stage should be noted because death of Purkinje cells of the cerebellum leads to degeneration of their axons and subsequently to the decrease of grumose degeneration in the dentate nucleus. Familial PSP have been reported by several authors but all case in the present study were sporadic.
Brain tissue microarrays in neurodegenerative diseases: Validation of methodology and immunohistochemical study of growth‐associated protein‐43 and calretinin
Authors: Takei Hidehiro , Buckleair Linda W. , Rivera Andreana , Powell Suzanne Z.
Published: November 2007

A tissue microarray (TMA) was constructed using 47 neurodegenerative diseases (NDD), including Alzheimer's disease (AD; n = 30) and non‐AD NDD (n = 17), and from seven controls. For validation of the methodology, the following three immunostains were used. Tau and β‐amyloid‐related pathologies were more significantly recognized in tauopathies/AD compared to non‐tauopathies/controls, and these results were comparable to the assessment of the whole brain sections. But no α‐synuclein pathologies were observed despite five cases of dementia with Lewy bodies. It was concluded that the TMA technique is useful for NDD with diffuse pathological processes but not for those with patchy and occasional lesions or in early stages. Growth‐associated protein (GAP)‐43 and calretinin were also immunostained. A significant reduction in GAP‐43 expression was seen in the frontal lobe and hippocampus in AD compared to non‐AD cases, but not in other areas. No significant difference in number of anticalretinin immunoreactive neurons or in density of immunoreactive neurites was observed between any of the NDD and controls, which may indicate that calretinin‐positive neurons are spared in the degenerative process. These results are compatible with the previous studies. These analyses were performed rapidly in a large number of cases using a single slide under uniform staining conditions.
Clinical outcome of radical cystectomy for patients with pT4 bladder cancer
Authors: Furukawa Junya , Miyake Hideaki , Hara Isao , Takenaka Atsushi , Fujisawa Masato
Published: October 2007

Objective:  The objective of this study was to analyze the outcomes of radical cystectomy for patients with pT4 bladder cancer.

Methods:  Between 1995 and 2003, 583 patients underwent radical cystectomy for bladder cancer at our institution and related hospitals, including 76 pathologically diagnosed as having pT4 disease. Of these 76, this study included 60 patients after excluding 16 with pT4Tis disease, and a retrospective review of their records was carried out.

Results:  Pathological examinations demonstrated that seven (11.6%) and 53 (88.4%) patients were Grades 2 and 3, respectively, and 48 (80.0%), 38 (63.4%), 10 (16.7%) and 30 (50.0%) were positive for lymphatic invasion, microvenous invasion, surgical margin and lymph node metastasis, respectively. During the observation period of this study (median, 24.5 months; range, 2–89 months), disease recurrence occurred in 38 (63.3%), and the median time to recurrence after radical cystectomy was 7.0 months (range, 1–38 months). One‐, 3‐ and 5‐year cancer‐specific survival rates of the 60 patients were 68.8%, 48.5% and 23.9%, respectively. Univariate analysis identified lymph node metastasis, lymphatic invasion, microvenous invasion and positive surgical margin as significant predictors for cancer‐specific survival; however, only lymph node metastasis was shown to be independently associated with cancer‐specific survival by multivariate analysis.

Conclusions:  The prognosis of patients with pT4 bladder cancer is generally poor, particularly for those with nodal involvement. Therefore, it would be potentially important to carry out careful follow‐up for such patients following radical cystectomy and, if necessary, to consider a multimodal therapeutic approach in an adjuvant setting.
Surgical treatment for stress urinary incontinence
Authors: Harding Chris K , Thorpe Andrew C
Published: October 2007

Abstract:  The prevalence of stress urinary incontinence is quite significant with large numbers of women affected. Many of these women will not seek medical help in the belief that they will not be cured or improved. With the increasing numbers of procedures now available we present a review of both established and novel surgical techniques that is intended to help both urologists and primary care physicians in the counselling of patients complaining of stress incontinence. We compare the “gold standards” of surgical treatment for all types of stress incontinence with the newer techniques that have recently become popular among urologists and gynaecologists.
Acute effect of metformin on exercise capacity in active males
Authors: Johnson S. T. , Robert C. , Bell G. J. , Bell R. C. , Lewanczuk R. Z. , Boulé N. G.
Published: October 2007

Aim:  Physical activity and metformin are often used concomitantly in the treatment of diabetes, even though little is known about possible interactions between these treatment modalities. This study was designed to examine the acute effect of metformin on oxygen consumption and lactate concentration during exercise.

Methods:  Eleven healthy, active men [mean ± s.d.: age = 29.9 ± 3.7 years; body mass index = 25.2 ± 2.8 kg/m2; maximal oxygen consumption (VO2max) = 53.5 ± 8.9 ml/kg/min] completed a randomized, double‐blind, placebo‐controlled, crossover study. The testing protocol consisted of a standardized breakfast with metformin (1000 mg) or placebo. Three hours after breakfast, participants underwent a graded maximal exercise test on a cycle ergometer. Approximately 30 min after this exercise test, participants cycled continuously at an intensity below their ventilatory threshold for 45 min (mean exercise intensity = 69 ± 5.5% of VO2max).

Results:  During the graded exercise test, average oxygen consumption was higher for the metformin condition (2.9 vs. 2.8 l/min, p = 0.04); however, there was no treatment effect on VO2max or ventilatory threshold. During continuous exercise, lactate was lower for the metformin condition (4.7 vs. 5.4 mmol/l, p = 0.05). Following a standardized lunch, glucose concentrations were lower in the metformin compared with the placebo condition (5.8 vs. 6.4 mmol/l, p = 0.04).

Conclusion:  A single dose of metformin does not acutely influence maximal oxygen consumption or ventilatory threshold in healthy active males. The lower lactate concentration observed during continuous exercise with metformin was an unexpected finding considering that, in the resting state, metformin has been previously associated with a modest increase in lactate concentrations.
Effect of chronic rosiglitazone, metformin and glyburide treatment on β‐cell mass, function and insulin sensitivity in mZDF rats
Authors: Atkinson L. L. , McDonald‐Dyck C. , Benkoczi C. , Finegood D. T.
Published: October 2007

Here we investigate the effect of rosiglitazone (RSG), metformin (MET) and glyburide (GLIB) on plasma glucose levels, β‐cell mass, function and insulin sensitivity in 10‐week‐old diabetic male Zucker diabetic fatty (mZDF) rats using quantitative morphometry and a mathematical model β‐cell mass, insulin and glucose kinetics (βIG). At treatment start, 10‐week‐old diabetic mZDF rats were severely hyperglycaemic and had very low β‐cell function (insulin secretory capacity). RSG treatment significantly lowered plasma glucose levels in 67% of the mZDF rats. MET was effective at lowering plasma glucose levels in 33% of the mZDF rats, while GLIB was completely ineffective at lowering blood glucose levels in 10‐week‐old mZDF rats. RSG treatment prevented the fall in β‐cell mass after 6–8 weeks of treatment accompanied by a significant decrease in β‐cell death while MET treatment had no effect on β‐cell mass. RSG treatment increased insulin sensitivity 10‐fold, increased β‐cell function fivefold and modestly increased β‐cell mass 1.4‐fold. MET treatment increased insulin sensitivity fourfold, with no significant effect on β‐cell function or mass. Although RSG treatment was highly successful in lowering plasma glucose levels, the 33% of mZDF rats that did not respond to the treatment had significantly lower β‐cell function prior to treatment start compared with the responder group. Thus, the low level of β‐cell function at treatment start may explain why none of these agents were completely effective at lowering blood glucose levels in 10‐week‐old diabetic mZDF rats. Nevertheless, these data suggest that the preservation of β‐cell mass and improvement in β‐cell function play a role in the overall beneficial effect of RSG in 10‐week‐old diabetic mZDF rats.
How to identify patients with vulnerable plaques
Authors: Virani Salim S. , Ballantyne Christie M.
Published: October 2007

Multiple strategies are available for clinicians to identify patients at high risk for cardiovascular events. Two commonly discussed strategies are the identification of vulnerable plaques and the identification of vulnerable patients. The strategy of identifying vulnerable patients is less invasive, easy to implement and not restricted primarily to one vascular bed (e.g. coronary or cerebral). This review discusses the utility as well as the limitations of global risk assessment tools to identify such patients. The utility of biomarkers [C‐reactive protein, lipoprotein‐associated phospholipase A2 and lipoprotein(a)] and non‐invasive measures of atherosclerosis burden (coronary artery calcium scores, carotid intima–media thickness and ankle–brachial index) in identifying patients at high risk for cardiovascular events are also discussed.
Vascular and neural dysfunction in Zucker diabetic fatty rats: a difficult condition to reverse
Authors: Oltman C. L. , Davidson E. P. , Coppey L. J. , Kleinschmidt T. L. , Lund D. D. , Adebara E. T. , Yorek M. A.
Published: October 2007

Aim:  We had previously demonstrated that vascular and neural dysfunction in Zucker diabetic fatty (ZDF) rats is progressive. In this study, we sought to determine whether monotherapy of ZDF rats can reverse the vascular and nerve defects.

Methods:  ZDF rats at 16 weeks of age were treated for 12 weeks with the angiotensin‐converting enzyme inhibitor enalapril, the antioxidant α‐lipoic acid, the HMG‐CoA reductase inhibitor rosuvastatin or the PPARγ agonist rosiglitazone. Vasodilation of epineurial arterioles was measured by videomicroscopy. Endoneurial blood flow (EBF) was measured by hydrogen clearance, and nerve conduction velocity was measured following electrical stimulation of motor or sensory nerves.

Results:  Motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV) (70 and 77% of control, respectively), EBF (64% of control), and vascular relaxation in response to acetylcholine (50% of control) and calcitonin gene‐related peptide (CGRP; 73% of control) are impaired in ZDF rats at 28 weeks of age compared with lean littermate controls. Treatment with enalapril and α‐lipoic acid attenuated the decrease in MNCV and SNCV. Enalapril, α‐lipoic acid and rosiglitazone treatment of ZDF rats were partially effective in improving endothelium‐dependent vascular dysfunction as measured by vascular relaxation in response to acetylcholine. The same drugs also attenuated the decrease in EBF. However, impairment in vascular relaxation in response to CGRP was improved with only α‐lipoic acid or rosuvastatin treatment. The increase in superoxide and nitrotyrosine levels in vascular tissue was attenuated by all treatments.

Conclusions:  The efficacy of monotherapy treatment of ZDF rats using different classes of drugs for vascular and neural dysfunction once complications have developed did not achieve expected levels. This could be because of the complex aetiology of vascular and neural disease in type 2 diabetes.
Evidence for a Data‐Based Environmental Policy: Induction of a Behavior‐Based Decision Support System
Authors: Kaiser Florian G. , Midden Cees , Cervinka Renate
Published: October 2007

To advise policy‐makers about possible courses of action in the environmental domain, psychological science should employ a support system that allows for evidence‐based decisions with respect to the three generic policy questions: what, where, and how. The key to such a system is a measurement instrument in which environmental motivation becomes tangible in individual actions. In this article, we provide empirical examples of such a decision support system in the environmental domain. It consists of (a) evidence about environmental motivation of persons, (b) evidence about motivation's spatial distribution, (c) knowledge about the socio‐cultural conditions that affect individuals when they translate motivation into action (i.e. structural information), and (d) a forecast of the environmental impact—the concrete conservation potential of various behaviors.

Pour conseiller les décideurs à propos de lignes de conduite possibles dans le domaine de l’environnement, la science psychologique devrait utiliser un système qui tienne compte des décisions provenant des trois questions génériques suivantes: quoi, ou et comment? La clé d’un tel système consiste en un instrument de mesure dans lequel la motivation environnementale devient tangible dans les actions individuelles. Dans cet article, nous prenons des exemples empiriques de telles aides à la décision dans le domaine de l’environnement. Peut être ainsi montré a) la motivation environnementale des personnes, b) la distribution spatiale de la motivation, c) l’influence de la connaissance des conditions socioculturelles des individus quand ils transforment motivation en action (i.e. information structurale) et (d) la prévision de l’impact environnemental sur le maintien potentiel de divers comportements.
Quality of diabetes care in the UK: comparison of published quality‐of‐care reports with results of the Quality and Outcomes Framework for Diabetes
Authors: Khunti K. , Gadsby R. , Millett C. , Majeed A. , Davies M.
Published: October 2007

Aims  To conduct a systematic review of published observational studies of quality of diabetes care in primary care in the UK and to compare the results with the quality of care data from the Quality and Outcomes Framework (QOF) of the new General Practice Contract in the UK.

Methods  medline and embase were searched for articles published from 1999 to June 2006. We also searched for reference lists of studies that fitted our inclusion criteria. All members of the Primary Care Diabetes Europe were contacted and asked to send lists of any relevant published articles. Abstracts were reviewed and data were collected independently by two authors.

Results  Abstracts of 742 papers were identified, of which six papers fulfilled the final selection criteria. The total number of people included in the six published studies was 83 098 (a range of 504 to 54 180 people) compared with the UK QOF data of 1.8 million people with diabetes. The quality indicators for assessment of care varied between different published studies, making comparisons more difficult. Overall, there was a trend towards improvement in both process and outcome of care in the published studies. The quality of care achieved as a result of QOF was greater than that found in published studies.

Conclusions  There have been improvements in both process and outcome measures recorded in publications of quality of diabetes care in the UK between 2000 and 2004. Modest financial incentives in primary care are a successful method of improving care for people with diabetes.
Inverse correlation between activated protein C generation and carotid atherosclerosis in Type 2 diabetic patients
Authors: Matsumoto K. , Yano Y. , Gabazza E. C. , Araki R. , Bruno N. E. , Suematsu M. , Akatsuka H. , Katsuki A. , Taguchi O. , Adachi Y. , Sumida Y.
Published: October 2007

Aims  Activated protein C (APC) is a key regulator of the clotting system and immune responses. We studied the relationship between the degree of atherosclerosis as measured by the intima‐media thickness (IMT) of carotid artery and APC generation in Type 2 diabetic patients.

Methods  Eighty‐seven Type 2 diabetic patients and 35 control subjects participated. APC generation was assessed by the plasma APC–protein C inhibitor complex (APC‐PCI) levels and the mean IMT of carotid artery was measured by ultrasonography. The plasma levels of the thrombin–anti‐thromobin complex (TAT) and platelet‐derived growth factor (PDGF) were measured by enzyme‐linked immunoassays.

Results  Plasma TAT levels were significantly higher in diabetic patients [2.03 (1.12, 2.56) ng/ml, median (25th, 75th percentile)] compared with control subjects [0.85 (0.55, 2.08) ng/ml, P < 0.01]. Plasma APC‐PCI levels were significantly lower in diabetic patients [0.93 (0.74, 1.22) ng/ml], than in control subjects [1.66 (1.25, 2.36) ng/ml, P < 0.001]. The mean IMT was significantly increased in diabetic patients (0.881 ± 0.242 mm; mean ± sd) compared with control subjects (0.669 ± 0.140 mm; P < 0.01). Univariate analysis showed a significant and inverse correlation between plasma APC‐PCI levels and mean IMT (r = –0.32, P < 0.005), and multivariate regression analysis confirmed the independent correlation (P < 0.05). Moreover, plasma APC‐PCI levels significantly and inversely correlated with plasma PDGF levels in diabetic patients (r = –0.30, P < 0.01).

Conclusions  These results suggest that decreased APC generation is associated with vascular atherosclerotic changes in Type 2 diabetic patients.
A low‐carbohydrate diet is more effective in reducing body weight than healthy eating in both diabetic and non‐diabetic subjects
Authors: Dyson P. A. , Beatty S. , Matthews D. R.
Published: October 2007

Background  Low‐carbohydrate diets are effective for weight reduction in people without diabetes, but there is limited evidence for people with Type 2 diabetes.

Aims  To assess the impact of a low‐carbohydrate diet on body weight, glycated haemoglobin (HbA1c), ketone and lipid levels in diabetic and non‐diabetic subjects.

Methods  Thirteen Type 2 diabetic subjects (on diet or metformin) and 13 non‐diabetic subjects were randomly allocated to either a low‐carbohydrate diet (≤ 40 g carbohydrate/day) or a healthy‐eating diet following Diabetes UK nutritional recommendations and were seen monthly for 3 months. Subjects (25% male) were (mean ± sd) age 52 ± 9 years, weight 96.3 ± 16.6 kg, body mass index 35.1 kg/m2, HbA1c 6.6 ± 1.1%, total cholesterol 5.1 ± 1.1 mmol/l, high‐density lipoprotein cholesterol 1.3 ± 0.4 mmol/l, low‐density lipoprotein cholesterol 3.1 ± 0.9 mmol/l, triglycerides (geometric mean) 1.55 (1.10, 2.35) mmol/l and ketones range 0.0–0.2 mmol/l.

Results  Analysis was by intention to treat with last observation carried forward. Twenty‐two of the participants (85%) completed the study. Weight loss was greater (6.9 vs. 2.1 kg, P = 0.003) in the low‐carbohydrate group, with no difference in changes in HbA1c, ketone or lipid levels.

Conclusions  The diet was equally effective in those with and without diabetes.
How to be Bicameral: Reading William Connolly's Pluralism with Whitehead and Deleuze
Authors: Williams James
Published: November 2007

This article argues that the concept of bicameralism is central to William Connolly's pluralism. The concept is analysed in terms of its roots in political bicameralism, in the bicameral mind and in organic bicameralism in order to show its richness and its capacity to provide positive answers to a series of standard criticisms of pluralism. Two more persistent critical problems are presented in the problem of evil (can we afford to be open to other political positions if they are evil?) and in the problem of the generation of paradoxes (does pluralism depend on adopting perniciously paradoxical positions?). These questions are answered by drawing connections from Connolly's work to Alfred North Whitehead's definition of evil and to Gilles Deleuze's work on paradox.
William E. Connolly: Pluralism without Transcendence
Authors: Wenman Mark
Published: November 2007

In the context of multiculturalism and identity politics the concept of ‘pluralism’ has become the common sense of our times. Here, I mark out the distinctiveness of William Connolly's approach to pluralism vis-à-vis the neo-Kantian perspectives of John Rawls and Jurgen Habermas. Unlike the neo-Kantian perspectives, Connolly's account of ‘network pluralism’ denies the possibility of any element of transcendence from the plurality of forces that make up the world. Having explored the role that ‘agonistic respect’ plays in Connolly's version of pluralism, I make the case that his thought retains traces of (Spinozan pan-) theism, in the sense that he imagines that forms of regularity tend to emerge spontaneously from the immanent movement of social forces. The paper concludes with intimations of an alternative account of social regularity, one that emphasises the transcendental moment understood as necessary/impossible.