bluuebunny/crossref_metadata_2025 huggingface dataset:
Conclusion
Authors: Mason Andrew
Published: May 2007

This concluding chapter presents a synthesis of the topics discussed in this volume. Against the idea that justice requires us to neutralize the effects of differences in people's circumstances, it has been argued that it requires us merely to mitigate these effects, to prevent them from having an undue impact upon people's relative access to advantage. Competing versions of this mitigation approach include different sets of principles, which give different determinations of what is to count as an ‘undue effect’. Such principles are defended and this provides a vision of what it is to level the playing field that is rather different, at least at the level of fundamentals, from what is in the neutralization approach.
Courage and Caution
Authors: Roberts Robert C. , Wood W. Jay
Published: May 2007

Courage and caution enable us to find our way among the threats, real and apparent, that we encounter in the course of our practices, sometimes circumventing these threats, sometimes facing them, and sometimes paying their price. When the practice in question is intellectual (research, teaching, investigative reporting, etc.), courage and caution are intellectual virtues. Courage and caution in general do not have an intrinsic structure of motivation, but when we specify them as intellectual virtues, then the love of knowledge is their proper motive. Like other human activities, intellectual ones are fraught with threats — pitfalls, dangers, and difficulties — both apparent and real. The real threats must be respected, yet not allowed to deter the agent from the pursuit of the intellectual goods. The merely apparent ones must be assessed as such, and the resulting fears well managed.
The Epworth Experience
Authors: Lloyd Gareth
Published: May 2007

Charles Wesley was a complex man in terms of his denominational identity and this ambiguity is reflected in the Methodist movement that he helped to found. Some of the keys to understanding Charles Wesley and his relationship with Methodism, the wider Evangelical Revival, and the Church of England can be found in a childhood shaped by a difficult environment and parents whose own denominational identities were a rich mix of Puritan and High Church Anglican tempered by influences from other Christian traditions. These same ingredients proved to be of fundamental importance in the making of Methodism.
Engagements and Marriages
Authors: Lloyd Gareth
Published: May 2007

The marriage of Charles Wesley to Sarah Gwynne in April 1749 represented a watershed in the groom's life and ministry. Charles's itinerant preaching was reduced until it ceased altogether in 1756 and this aggravated other tensions that were starting to appear in relations between the Wesley brothers. John and Charles seem to have viewed each other's marital intentions as a threat and this climaxed in Charles's deliberate destruction of his brother's engagement to Grace Murray in October 1749. A decisive personal break between the brothers was only narrowly avoided, but their old closeness was severely undermined and this alienation started to impact on the Methodist movement.
Methodism in the Early 1750s
Authors: Lloyd Gareth
Published: May 2007

By 1749 Methodism had put down firm roots in communities across the British Isles. The movement's size and the increasing sophistication of its structure and worship life imposed a distance with the parent Church of England and this was worsened by the hostility of many Anglicans. Some Methodist preachers started to react against the Church and also against the discipline imposed by the Wesley brothers. The rising tension boiled over in 1754 when preachers in London and Reading administered the Sacraments contrary to Anglican practice. The resulting crisis was worsened by Charles Wesley's suspicion that his brother was sympathetic to the separatists. John eventually decided against separation from the Church of England, but his brother's fears for the future were not eased, establishing a pattern for the future of his relationship with John Wesley and the Methodist movement.
7 Paris and Democracy, 1990
Authors: Clark Ian
Published: May 2007

As part of the ending of the Cold War, a summit of the Conference on Security and Cooperation in Europe agreed the Charter of Paris in 1990. Amongst other things, it expressed a commitment to democracy ‘as the only system of government of our nations’. If international society is considered to be pluralistic, this was a puzzling development: it was making an international principle of legitimacy out of a form of internal government. The chapter attempts to explain this development in terms of the role of world society, in the context of the dramatic events of the end of the Cold War. It shows that the commitment to democracy served obvious state purposes, but also responded to a wider social constituency of expectations. This case was pressed by a transnational network acting in support of democratic principles, and which organized parallel summits to shadow the CSCE process. This also responded to developments in international law where some theorists, such as Thomas Franck, claimed to have identified an emerging democratic entitlement.
Conclusion
Authors: Clark Ian
Published: May 2007

The first part of the conclusion summarizes the findings from the historical cases. These fall into four categories. The first is where a strong world society constituency is able to influence the policy of a leading state, or group of leading states, as in the case of the slave trade or social justice in 1919. In the second case, the same holds true, but it is actually the leading states that proactively encourage world society action, as with human rights at San Francisco. In the third case, as at The Hague, there was no specific state ‘norm entrepreneur’. Fourthly, there is the negative case where the state sponsor was not strong enough to have the norm accepted, as with Japan and racial equality in 1919. Theoretically, the argument points to a degree of normative assimilation between international and world society, and a corresponding degree of social integration. The relationship is one of complementariness rather than displacement. This develops English School discussions of the topic. However, there is a warning that past coalitions between world society groups and leading states — that seem to have stimulated humanitarian norms — could in the future promote less attractive norms.
A letter written to the publisher concerning a new way, by an English manufacture to preserve the hulls of ships from the worm, &c; better for sailing and more cheap and durable than any sheathing or graving hitherto used
Authors: Bulteel John
Published: May 2007

Sir
, Understanding you have the trouble to publish such new and profitable Experiments as come to your knowledge, I take the liberty to inform you of a New Invention, which hath and no doubt will be of very great benefit and advantage to the public.
An exact account of the three late conjunctions of Saturn and Jupiter, (within the space or less than seven months according to accurate observations) viz. Octob. 14.82, &c. Together with an account of what other conjunctions of them there happened for more than 100: years last; beginning at the year 1563: and a table computed whereby to make an estimate of what other conjunctions have happened for the time past, or that will happen for the time to come
Authors: Flamsteed John
Published: May 2007

Whilst the common people have admired to see the two superior planets
Saturn
and
Jupiter
continue so near each other this whole year, and our astrologers have affrighted them with fearful predictions of direful events to succede this appearance, the more judicious are desirous to know how often and at what time their conjunctions happen, that by compareing their tables of these planets motions with the observed apperance, they may be better able to correct them and render them more agreeable to the heavens.
Racial disparity in stage at diagnosis and survival among adults with oral cancer in the US
Authors: Shiboski Caroline H. , Schmidt Brian L. , Jordan Richard C. K.
Published: May 2007

Abstract  Objectives:  To explore distribution of stage at diagnosis and relative survival rates among US adults with oral cavity cancer in relation to race, and over time.

Methods:  We obtained 1973–2002 oral cancer incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program, and computed proportions for each oral cavity site by stage at diagnosis, tumor size, and 5‐year relative survival rates among Whites and Blacks.

Results:  A total of 46 855 cases of oral cavity cancer were reported to the SEER registry among adults ≥20 years between 1973 and 2002. African–Americans had a significantly higher proportion of cancer, mainly in the tongue, that had spread to a regional node or to a distant site at diagnosis than Whites: 67% versus 49% of tongue cancers reported from 1973 to 1987 (P < 0.001), and 70% versus 53% of those reported from 1988 to 2002 (P < 0.001). They had a significantly higher proportion of tongue cancer that were >4 cm in diameter at time of diagnosis (59% versus 44%; P < 0.001), and black men in particular experienced lower 5‐year relative survival rates than white men, in particular, for tongue cancer (25% versus 43% from 1973 to 1987, and 31% versus 53% from 1988 to 2002).

Conclusion:  There are significant racial disparities with respect to stage at diagnosis and survival among adults with oral cancer reported to the SEER registry from 1973 to 2002. One possible explanation for the lower survival among Blacks may be a difference in access to, and utilization of, healthcare services.
Immunocytochemical localization of pleurocidin to the cytoplasmic granules of eosinophilic granular cells from the winter flounder gill
Authors: Murray H. M. , Leggiadro C. T. , Douglas S. E.
Published: May 2007

The teleost gill is considered to be of significant immunological importance, as it is one of the first tissues exposed to environmental or pathogenic challenge and thus should be well equipped to mount an effective immune response. This study characterizes ultrastructurally and immunocytochemically a tissue granulocyte (eosinophilic granular cell) from the winter flounder gill that was previously determined to be involved in the gene expression and synthesis of a known antimicrobial peptide (pleurocidin). The cell is irregular in shape with a cytoplasm characterized by numerous large, electron‐dense, membrane‐bounded granules. The nucleus is euchromatic and closely associated with a prominent rough endoplasmic reticulum. The cytoplasm typically contains two to three mitochondria and a centralized Golgi apparatus surrounded by numerous electron‐lucent vesicles. Immunogold staining of the cells with an anti‐pleurocidin antibody shows large number of gold particles in direct association with the electron‐dense granules. These data provide the first evidence definitively showing storage of an antimicrobial peptide in the cytoplasmic granules of an eosinophilic granule cell resident in gill tissue.
Actin filaments‐stabilizing and ‐bundling activities of cofilin‐phosphatase Slingshot‐1
Authors: Kurita Souichi , Gunji Emi , Ohashi Kazumasa , Mizuno Kensaku
Published: May 2007

Slingshot‐1 (SSH1) is known to regulate actin filament dynamics by dephosphorylating and activating cofilin, an actin‐depolymerizing factor. SSH1 binds to filamentous (F‐) actin through its multiple F‐actin‐binding sites and its cofilin‐phosphatase activity is enhanced by binding to F‐actin. In this study, we demonstrate that SSH1 has F‐actin‐stabilizing and ‐bundling activities. In vitro actin depolymerization assays revealed that SSH1 suppressed spontaneous and cofilin‐induced actin depolymerization in a dose‐dependent manner. SSH1 inhibited F‐actin binding and severing activities of cofilin. Low‐speed centrifugation assays combined with fluorescence and electron microscopic analysis revealed that SSH1 has F‐actin‐bundling activity, independently of its cofilin‐phosphatase activity. Deletion of N‐ or C‐terminal regions of SSH1 significantly reduced its F‐actin‐stabilizing and ‐bundling activities, indicating that both regions are critical for these functions. As SSH1 does not form a homodimer, it probably bundles F‐actin through its multiple F‐actin‐binding sites. Knockdown of SSH1 expression by RNA interference significantly suppressed stress fiber formation in C2C12 myoblast cells, indicating a role for SSH1 in stress fiber formation or stabilization in cells. SSH1 thus has the potential to regulate actin filament dynamics and organization in cells via F‐actin‐stabilizing and ‐bundling activities, in addition to its ability to dephosphorylate cofilin.
Two‐step, extensive alterations in the transcriptome from G0 arrest to cell division in Schizosaccharomyces pombe
Authors: Shimanuki Mizuki , Chung Soo‐Yoel , Chikashige Yuji , Kawasaki Yosuke , Uehara Lisa , Tsutsumi Chihiro , Hatanaka Mitsuko , Hiraoka Yasushi , Nagao Koji , Yanagida Mitsuhiro
Published: May 2007

Body cells in multicellular organisms are in the G0 state, in which cells are arrested and terminally differentiated. To understand how the G0 state is maintained, the genes that are specifically expressed or repressed in G0 must be identified, as they control G0. In the fission yeast Schizosaccharomyces pombe, haploid cells are completely arrested under nitrogen source starvation with high viability. We examined the global transcriptome of G0 cells and cells on the course to resume vegetative growth. Approximately 20% of the transcripts of ~5000 genes increased or decreased more than fourfold in the two‐step transitions that occur prior to replication. Of the top 30 abundant transcripts in G0, 23 were replaced by ribosome‐ and translation‐related transcripts in the dividing vegetative state. Eight identified clusters with distinct alteration patterns of ~2700 transcripts were annotated by Gene Ontology. Disruption of 53 genes indicated that nine of them were necessary to support the proper G0 state. These nine genes included two C2H2 zinc finger transcription factors, a cyclin‐like protein implicated in phosphorylation of RNA polymerase II, two putative autophagy regulators, a G‐protein activating factor, and two CBS domain proteins, possibly involved in AMP‐activated kinase.
Critical role of the p400/mDomino chromatin‐remodeling ATPase in embryonic hematopoiesis
Authors: Ueda Takeshi , Watanabe‐Fukunaga Rie , Ogawa Hironori , Fukuyama Hidehiro , Higashi Yujiro , Nagata Shigekazu , Fukunaga Rikiro
Published: May 2007

The SWI2/SNF2 family ATPase, p400/mDomino, is a core subunit of a large chromatin‐remodeling complex, and is currently suggested to play a unique function in histone variant exchange, a process by which chromatin structure is altered. Here, we investigated the role of p400/mDomino in mammalian development by generating mutant mice with a targeted deletion of the N‐terminal domain of p400/mDomino (referred to as mDomΔN/ΔN). The mDomΔN/ΔN mice died on embryonic day 11.5 (E11.5), and displayed an anemic appearance and slight deformity of the neural tube. DNA microarray and quantitative RT‐PCR analyses revealed that all of the embryonic globin genes and a globin chaperone gene were poorly expressed in the mDomΔN/ΔN embryo and yolk sac on E8.5, indicating that primitive erythropoiesis was impaired. A hematopoietic colony assay indicated that the hematopoietic activity of the yolk sac was significantly blocked in the mutant mice. We also found that the expression of a limited set of Hox genes, including Hoxa7, Hoxa9 and Hoxb9, was drastically enhanced in the mDomΔN/ΔN yolk sacs. These results suggest that p400/mDomino plays a critical role in embryonic hematopoiesis by regulating the expression of developmentally essential genes such as those in the Hox gene cluster.
Denture‐related stomatitis: identification of aetiological and predisposing factors – a large cohort
Authors: FIGUEIRAL M. H. , AZUL A. , PINTO E. , FONSECA P. A. , BRANCO F. M. , SCULLY C.
Published: May 2007

Summary  The aim of this study was to identify and characterize aetiological and predisposing factors in denture‐related stomatitis (DRS), by means of a case–control, transversal study, in a large cohort of 140 persons wearing removable maxillary polymethylamethacrylate prostheses. Data were obtained by (1) a questionnaire that included the identification of the subject, demographic and social data, medical history and behaviour; (2) intra‐oral examination; (3) evaluation of the prosthesis; (4) microbiological examination; (5) yeast identification and analyses using Epi‐info and the chi‐square test. Results showed significant associations between DRS and yeasts, gender, age and alcohol consumption. We also found a significant relationship between the presence of yeasts and hyposalivation and decreased salivary pH. We found a highly significant difference between groups with and without DRS concerning the presence or absence of yeasts, regardless of the sample origin. Most cases of DRS showed the presence of Candida albicans. The results confirm a highly significant difference between groups with and without DRS concerning the presence or absence of yeasts.
Kinetics of leaf oxygen uptake represent in planta activities of respiratory electron transport and terminal oxidases
Authors: Laisk Agu , Oja Vello , Eichelmann Hillar
Published: May 2007

We present, for the first time, the oxygen response kinetics of mitochondrial respiration measured in intact leaves (sunflower and aspen). Low O2 concentrations in N2 (9–1500 ppm) were preset in a flow‐through gas exchange measurement system, and the decrease in O2 concentration and the increase in CO2 concentration as result of leaf respiration were measured by a zirconium cell O2 analyser and infrared‐absorption CO2 analyser, respectively. The low O2 concentrations little influenced the rate of CO2 evolution during the 60‐s exposure. The initial slope of the O2 uptake curve on the dissolved O2 concentration basis was relatively constant in leaves of a single species, 1.5 mm s−1 in sunflower and 1.8 mm s−1 in aspen. The apparent K0.5(O2) values ranged from 0.33 to 0.67 μM in sunflower and from 0.33 to 1.1 μM in aspen, mainly because of the variation of the maximum rate, Vmax (leaf temperature 22°C). The initial slope of the O2 response of respiration characterizes the catalytic efficiency of terminal oxidases, an important parameter of the respiratory machinery in leaves. The plateau of the response characterizes the activity of the mitochondrial electron transport chain and is subject to regulations in accordance with the necessity for ATP production. The relatively low oxygen conductivity of terminal oxidases means that in leaves, less than 10% of the photosynthetic oxygen can be reassimilated by mitochondria.
Impact of ultraviolet radiation on physiology and development of zoospores of the brown alga Alaria esculenta from Spitsbergen
Authors: Wiencke Christian , Lüder Ulrike H. , Roleda Michael Y.
Published: May 2007

Zoospores of the brown alga Alaria esculenta from Spitsbergen were exposed in the laboratory to photosynthetically active radiation [(P), 400–700 nm], P + UVA radiation (PA, 320–700 nm) and PA + UVB radiation (PAB, 280–700 nm). Germination rates were determined, and the germination process was documented by light microscopy. In parallel, the presence of UV‐absorbing phlorotannins was studied. Photoinhibition and recovery of photosynthesis were monitored as well as DNA damage and repair. After 8 h of exposure to PAB, germination was inhibited. A 16‐h exposure to PA and PAB resulted in a dramatic reduction of germination rates. Phlorotannin‐containing physodes were observed in the peripheral cytoplasm and physode‐like bodies were found outside the spore, still attached to the zoospore as well as freely floating in the medium; this suggested exocytosis. The absorbance of spore suspensions below 300 nm was higher after 20 h exposure to P, PA and PAB compared with the dark treatment. About 50% of the radiation was absorbed by the zoospores, and the rest was absorbed by the medium, especially after PA and PAB exposure. In this way, harmful UV radiation is absorbed before reaching the cells and this is probably the major reason for the relatively low DNA damage after ≤8 h exposure to PAB. Under these conditions, DNA damage was efficiently repaired and there was a notable recovery of photosynthesis. However, after 16 h exposure to PA and PAB, the protective and repair mechanisms are surcharged and the zoospores degenerate. The results cast light on the potential impact of enhanced UVB radiation on a dominant component of the seaweed community on Spitsbergen because of stratospheric ozone depletion. The acclimation potential of zoospores of this species to UV radiation as demonstrated here is regarded as conferring a competitive advantage in recruitment over similar species in the upper sublittoral zone.
Neuropathology of human T lymphotropic virus type I‐associated myelopathy
Authors: Izumo Shuji , Umehara Fujio , Osame Mitsuhiro
Published: May 2007

In order to clarify pathogenesis of human T lymphotropic virus type I (HTLV‐I)‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) a detailed neuropathological analysis of eight autopsy patients with HAM/TSP was performed. Inflammatory infiltrates of mononuclear cells and degeneration of myelin and axons were noted in the middle to lower thoracic spinal cords and were extended continuously to the entire spinal cord. Horizontal distribution of inflammatory lesions was symmetric at any spinal levels. Immunohistochemical analysis demonstrated T cell dominance. The numbers of CD4+ T cells and CD8+ T cells were present in equal numbers in patients with shorter clinical course. Apoptosis of helper/inducer T cells were observed in the presence of TIA1+ cytotoxic T cells in these active inflammatory lesions. Inflammatory infiltrates were markedly decreased and CD8+/TIA1‐ T cells were predominated over CD4+ cells in patients with prolonged clinical course. HTLV‐I proviral deoxyribonucleic acid (DNA) amounts in the freshly frozen spinal cord measured by quantitative polymerase chain reaction (PCR) were well correlated with the numbers of infiltrated CD4+ cells. In situ PCR of HTLV‐I provial DNA using multi‐primar pairs demonstrated the presence of HTLV‐I infected cells exclusively in the mononuclear infiltrates of perivascular areas. From these findings, it is suggested that the target of the inflammatory process seen in HAM/TSP lesions may be HTLV‐I infected CD4+ T cells infiltrating the spinal cord.
Retinoic acid‐induced neuronal differentiation regulates expression of mRNAs for neurotrophins and neurotrophin receptors in a human embryonal carcinoma cell line NTera2
Authors: Satoh Jun‐ichi , Yukitake Motohiro , Kurohara Kazuhiro , Kuroda Yasuo
Published: May 2007

The expression of mRNAs for neurotrophins and neurotrophin receptors was examined in NTera2/cl.D1 (NT2) human embryonal carcinoma cells at various stages of retinoic acid (RA)‐induced neuronal differentiation using reverse transcription‐polymerase chain reaction and southern blot analysis in order to investigate the biological role of neurotrophins in the human neuronal differentiation. The expression of high steady levels of BDNF, NT‐3, NT‐4, and low‐affinity NGF receptor mRNAs was observed in both untreated NT2 cells and NT2‐derived differentiated neurons induced by RA treatment. The lower levels of expression of NGF, trkA, trkB, and trkC mRNAs were identified in untreated NT2 cells and their expression was elevated markedly following 4 week treatment with RA. The increased expression of NGF, trkB, and trkC mRNAs were stable in NT2‐derived differentiated neurons, while the expression of trkA mRNA was reduced substantially in these cells. These results indicate that mRNAs for a battery of neurotrophins and their receptors are coexpressed in NT2 cells and their expression is regulated by RA‐induced neuronal differentiation.
An autopsy case of AIDS initially presenting with symptoms of myelopathy
Authors: Minami Naoya , Doi Shizuki , Shima Kohji , Nakane Kazuyoshi , Tashiro Kunio , Nakamura Nishio , Fujioka Yasunori , Sata Tetsutaro , Nagashima Kazuo
Published: May 2007

An autopsy case of HIV encephalomyelopathy in a homosexual patient who initially presented with signs of myelopathy, such as urinary incontinence and spasticity of both legs, is reported. The pathological examination disclosed typical HIV encephalopathy with macrophages and multinucleated giant cells (MGC) in the cerebral white matter and loss of neurons of the cerebral cortex. The MGC contained HIV‐1 p24 antigen. The thoracic spinal cord was markedly atrophied with degeneration of both lateral tracts, and histologically characterized by gliosis and perivascular accumulation of macrophages. Vacuolar changes and HIV‐1 p24‐containing cells were not observed in the spinal cord. The present case indicates that myelopathy can occur as an initial sign in AIDS patients, even though its pathomechanism remains to be elucidated.
Basic pathology of corticobasal degeneration
Authors: Ikeda Kenji
Published: May 2007

A survey of 32 clinically and pathologically evaluated cases of corticobasal degeneration (CBD) revealed three subtypes of cortical lesions. Besides the main subgroup with frontoparietal atrophy, especially with degeneration around the central sulcus, there are at least two subtypes in which the degenerating focus shifts from the central region to the frontal or superior temporal region. Such diversity of degenerating areas of the cerebrum results in the clinical heterogeneity of CBD. In contrast to the diversity of cerebral lesions, affected nuclei in the subcortical regions are rather uniform and their distribution is of diagnostic value. Cytopathologically, CBD is characterized by several types of abnormal cytoskeletal structures in both neurons and glia. They have common epitopes with hyperphosphorylated tau except for ballooned neurons, which are regarded as a pathological hallmark of this disease. Massive Gallyas/tau‐positive structures consist of neurofibrillary tangles and pre‐tangles in neurons as well as astrocytic plaques, coiled bodies and argyrophilic threads in glia. A part of argyrophilic threads are proved to originate from neuronal element. There is discrepancy between poor formation of solid tangles and massive appearance of Gallyas/tau‐positive structures in CBD. The former is detectable by Bodian method whereas the latter is scarcely seen by conventional silver impregnations. This indicates that almost all of Gallyas/tau‐positive structures have poor inclination to form solid structures in CBD. Immunohistochemical study with an antibody to the exon 3‐derived epitope of tau indicates that the majority of Gallyas/tau‐positive structures in CBD originate from glial cells. Differences as well as overlaps between CBD and progressive supranuclear palsy are discussed.
The relationship of arterial hypertension to intracranial saccular aneurysms: Histometric assessment of the role of hemodynamic stress in terms of arterial medial hypertrophy
Authors: Ohtoh Takashi , Iwasaki Yuzo , Suzuki Hiroyoshi , Namba Yoshio
Published: May 2007

In order to elucidate hemodynamic characteristics of the circle of Willis in patients with saccular aneurysms and the causative relationship linking saccular aneurysms and hypertension, branches of the circle of Willis from 21 patients with ruptured aneurysms and of seven normotensive and eight hypertensive controls were histometrically investigated. The 21 aneurysm cases consisted of 12 single, four multiple and five single giant aneurysms. Among these 21 patients, 11 had no clinical history of systemic hypertension. Histometric analysis revealed that the average thickness of the media of the resistance vessels in the circle of Willis in all 21 patients was significantly greater than that of the normotensive control group (P < 0.001), and that the mean thickness of the whole aneurysm group was almost equal to that of the hypertensive control group (t= 0.102). Moreover, the difference between 11 aneurysm patients without clinical history of hypertension and 10 aneurysm patients with clinical history of hypertension was insignificant (t= 1.293). Based on these data, we conclude that an increased local hemodynamic stress with hypertensive alterations of the arterial wall is prerequisite for the development of cerebral saccular aneurysm even in patients without a history of systemic arterial hypertension.
Primary lateral sclerosis
Authors: Watanabe Ryo , Iino Mitsuharu , Honda Masao , Sano Jinyu , Hara Masamichi
Published: May 2007

An autopsy case of motor neuron disease in which only the upper motor neurons were involved is reported. A 64‐year‐old man presented with progressive dysarthria, dysphagia and spastic quadriparesis with no muscle atrophy or fasciculation. He became bedridden 1.5 years later and died of pneumonia 3 years and 3 months after onset. Neuropathological findings consisted of a decreased number of Betz cells in the motor cortex and degeneration of the pyramidal tracts in the brainstem and spinal cord. The motor nuclei of the brainstem and anterior horn cells in the spinal cord were preserved. Some anterior horn cells contained ubiquitin‐positive dense bodies. Many axonal spheroids were found in the pyramidal tract in the brainstem, most frequently in the cerebral peduncles of the midbrain. These clinicopathological features are in keeping with primary lateral sclerosis as previously reported, however, the presence of ubiquitin‐positive material in some anterior horn cells suggests there may be some motor nerve cell degeneration occurring simultaneously.
Vasculitis with predominantly leptomeningeal involvement in an AIDS patient
Authors: Büttner Andreas , Pfister Hans‐Walter , Quintern Jochen , Itoh Kyoko , Mehraein Parviz , Weis Serge
Published: May 2007

A case of a 45‐year‐old female AIDS patient with an unusual type of vasculitis is presented. Clinically, she exhibited hemiparesis, hemianopsia, oculomotor abnormalities, grand mal seizures, and multiple cerebral ischemic lesions. Neuropathologic examination revealed a necrotizing, lymphocytic vasculitis predominantly involving the leptomeningeal spaces in various anatomical locations. The vasculitis was most probably due to the primary effect of HIV‐1, as no other possible pathogenetic agent was isolated.
The pathogenesis of olivary changes in clioquinol intoxication
Authors: Koga Makoto , Tsutsumi Akira , Shirabe Teruo
Published: May 2007

Inferior olivary changes were found in the central nervous system of five patients with subacute myelo‐opticneuropathy induced by long‐term clioquinol administration. The histological findings in the olivary nuclei could not be distinguished from those seen in olivary hypertrophy due to other causes. In two of the five cases, dentate neurons were relatively well preserved. However, there were minor abnormalities in the neuropil of the dentate nuclei and amiculum olivae with loss of myelin and fibrous gliosis. These changes suggested that processes and efferent fibers of the dentato‐olivary system were degenerating and led to speculation that the olivary changes in clioquinol intoxication might be secondary to distal dominant axonopathy in the dentato‐olivary pathway.
Central nervous system lymphoma and Epstein‐Barr virus in immunocompetent patients in Thailand
Authors: Kasantikul Vira , Mutirangura Apiwat , Wannakrairot Pongsak , Pornthanakasem Wichai , Ruangvejvorachai Preecha , Sriuranpong Virote , Voravud Narin
Published: May 2007

A series of 11 apparently immunocompetent patients with primary non‐Hodgkin's lymphoma of the central nervous system (NHL‐CNS) together with six patients with systemic lymphoma involving the spinal cord and/or brain were studied for immunophenotyping and the presence of Epstein‐Barr virus (EBV). Immunohistochemistry and polymerase chain reaction (PCR) were performed on paraffin‐embedded tissues. Nine of 11 primary NHL‐CNS and all six secondary CNS lesions were of B cell origin. The EBV sequences were detected in six primary tumors and four systemic lesions by PCR while the immuno‐histochemical marker for the EBV‐latent membrane protein was positive in five primary lesions and three secondary neoplasms. Our results suggest that the association of EBV and NHL‐CNS is not only restricted to patients with immunosuppression but that it includes a broad spectrum of conditions in which this relationship occurs in patients without immunodeficiency. The mortality rate is high particularly in patients with EBV‐associated NHL‐CNS.
Neurons and neurofibrillary tangles in the hippocampal cortex in familial and sporadic Alzheimer's disease
Authors: Sasaki Kazuo , Fukutani Yuken , Mukai Masami , Cairns Nigel J. , Isaki Kiminori
Published: May 2007

Hippocampal pathology was morphometrically studied in six early onset familial Alzheimer's disease (FAD) patients and the results were compared with six early onset sporadic Alzheimer's disease (SAD) patients. Unaffected neurons, intracellular neurofibrillary tangles (I‐NFT) and extracellular neurofibrillary tangles (E‐NFT) were evaluated on the same sections in eight subdivisions of the hippocampal cortex, using Gallyas technique modified by a direct application of hematoxylin and eosin stain (Gallyas‐HE stain). The subdivisions were CA4, CA3, CA2, CA1, prosubiculum (PRO), subiculum and presubiculum (PRE), parasubiculum (PARA) and entorhinal cortex (ENT). Unaffected neuron densities in CA2, CA1 and PRE in FAD were significantly lower than those in SAD. In contrast, in ENT the unaffected neuron density in FAD was greater than that in SAD, but the difference was not significant. Extracellular neurofibrillary tangle densities in the subregions, other than ENT in FAD, were greater than those in SAD, while the E‐NFT density in ENT in FAD was lower than that in SAD. Neurofibrillary tangles (I‐NFT plus E‐NFT) densities in CA3, CA2, CA1 and PRO in FAD were significantly greater than those in SAD. These data suggest that cornu ammonis is affected more severely than is the ENT in early onset FAD. These findings indicate that hippocampal pathology in early onset FAD may be qualitatively as well as quantitatively different from that in early onset SAD.
Angioma of the choroid plexus: Personal experience of 42 cases and a review of the literature
Authors: Shuangshoti Shanop , Shuangshoti Samruay
Published: May 2007

Only 127 cases have been reported of choroidal angiomas, including the 42 examples cited in the present paper. The mean age of the 42 subjects examined in the present series was 15 years and the median was 1 month. The lateral ventricle was the most common location. Bilateral angiomas comprised 40% of lesions in the lateral ventricle, which is strikingly more common than in previous reports (8%). Most patients presented with signs and symptoms of intraventricular or subarachnoid hemorrhage. The lesion, however, was found accidentally in 15 cases (36%), particularly in the perinatal period. Associated developmental malformations were observed in 25 instances (59%), which often involved the cardiovascular system. The median age of 30 years of patients with choroid plexus angioma in the literature is significantly (P < 0.005) higher than that in the present study. Of 85 cases of choroidal angioma reported in the literature, only three cases (4%) were encountered accidentally. It is suggested that careful examination of the choroid plexus will increase the diagnosis of choroidal angiomas and that hemangiomas should be searched for in the choriod plexus in cases of intraventricular hemorrhage as well as in instances of developmental malformations, particularly those affecting the cardiovascular system.
Dysembryoplastic neuroepithelial tumor found incidentally in the hippocampus of an elderly patient
Authors: Shintaku Masayuki , Ogura Jun
Published: May 2007

A small tumorous lesion showing the histopathological appearance of a ‘simple form’ of dysembryoplastic neuroepithelial tumor (DNT) was found incidentally at autopsy in the hippocampus of an 80‐year‐old man who died of Parkinson's disease. Clinical symptoms of this lesion were not apparent. The lesion was predominantly composed of oligodendrocyte‐like small cells which were arranged along well‐developed capillaries forming an ‘alveolar structure’. The background showed a remarkably myxoid appearance, with many large neuronal cells floating within it. The surrounding hippocampal cortex did not show any dysplastic changes. This patient is the oldest among reported cases of DNT in the literature.
Chordoma in a child presenting as unilateral proptosis with high serum alpha‐fetoprotein
Authors: Kasantikul Vira , Tontiratanon Pawana , Wangsuphachart Somjai , Panichabhongse Viratt
Published: May 2007

A 14‐month‐old girl with intracranial chordoma involving the left orbit, paranasal sinuses, nasal cavity and hard palate presented with unilateral proptosis. The serum α‐fetoprotein was markedly elevated. Such intracranial tumors in infancy tend to be aggressive and have a great tendency for rapid growth as well as distant metastases.
The implications of genetic studies on the pathogenesis of Alzheimer's disease
Authors: Sasaki Hidenao
Published: May 2007

Current research in molecular genetics and molecular cell biology has disclosed that Alzheimer's disease (AD) is composed of a number of etiologically heterogenous disorders. In dominantly inherited early onset AD, the missense mutations found in the genes encoding amyloid precursor protein (APP), presenilin‐1, and/or presenilin‐2, are all known to increase the production and secretion of Aβ1–42(43). The abnormal deposition of Aβ1–42 is currently considered to play a key role in triggering a pathological array of symptoms in AD. Investigation of the molecular mechanism causing dominant AD provides a powerful model to understand the etiology of sporadic late‐onset AD, whose mechanism remains unknown.
Biochemical heterogeneity of Alzheimer's disease
Authors: Shoji Mikio , Harigaya Yasuo
Published: May 2007

Amyloid β protein (Aβ) amyloid deposition is an important early event in the evolution of Alzheimer's disease (AD) pathology. Serial extraction studies of AD brains showed that a large amount of modified Aβ (4, 3.7 and 3 kDa Aβ species) was accumulated as forms with differing solubilities. Immunostaining using specific antibodies to the N and C terminus of Aβ showed that N‐terminally modified Aβ ending at 42A were predominant in senile plaques. Quantitative assay of Aβ in AD brain revealed that Aβ ending at 40 V were correlated with vascular amyloids and that Aβ ending at 42(43) were related with senile plaque amyloids. The site of Aβ deposits may be determined by the heterogeneous length of the C terminus Aβ. The amount of Aβ amyloids may be correlated with N‐terminal modification of Aβ. Thus, heterogeneity of Aβ species is a crucial biochemical factor of AD pathogenesis.
The GDNF/Neurturin‐Ret multicomponent receptor system
Authors: Takahashi Masahide , Nakayama Seiko
Published: May 2007

Glial cell line‐derived neurotrophic factor (GDNF) and neurturin (NTN) are structurally related neurotrophic factors that play crucial roles in the survival of peripheral sensory, sympathetic and dopaminergic neurons as well as motoneurons. Glial cell line‐derived neurotrophic factordeficient mice showed lack of enteric neurons and renal agenesis or dysgenesis. Surprisingly, this phenotype was strikingly similar to that of ret proto‐oncogene‐deficient mice, suggesting that Ret tyrosine kinase might be a functional receptor for GDNF. Recent studies demonstrated that both GDNF and NTN were able to induce Ret tyrosine phosphorylation although they did not bind to Ret with high affinity, but novel glycosyl‐phosphatidylinositol (GPI)‐linked cell‐surface proteins as ligand‐binding components were required for Ret activation. Since GDNF and NTN are expected as therapeutic agents in neurodegenerative disorders such as Parkinson's disease and amyotrophic lateral sclerosis, the studies on the mechanisms of their biological actions through Ret would contribute to the development of new therapeutic strategies for these diseases.
Virus production, cell proliferation and cell death in progressive multifocal leukoencephalopathy
Authors: Sato‐Matsumura Kazuko C , Hainfellner Johannes A , Budka Herbert
Published: May 2007

Formalin fixed, paraffin embedded, progressive multifocal leukoencephalopathy (PML) brain lesions from eight stereotaxic needle biopsies and eight autopsies were immunocytochemically examined for tumor suppressor gene products (p53, retinoblastoma gene product, pRb), cell proliferation antigens (Ki‐67, proliferation nuclear antigen (PCNA)) and bcl‐2. The load of JC virus (JCV) was examined by immunocytochemistry for papovavirus common antigen and in situ hybridization for JCV‐DNA. DNA fragmentation was investigated with in situ endlabeling (ISEL). The virus markers, tumor suppressor gene products, and cell proliferation antigens were intensively expressed in infected oligodendrocytes (PML cells) and in bizarre astrocytes. The PML cells were labelled uniformly with virus markers, anti‐tumor suppressor gene products and anti‐cell proliferation antigens; however, the variance of the reactivity of the bizarre astrocytes was quite broad. The bcl‐2 was strongly expressed in infiltrating lymphocytes and reactive astrocytes, but not in oligodendroglia. Only few apoptotic bodies or nuclear fragments were labelled with ISEL in seven of eight cases. In seven of eight cases, some PML cells were labelled with ISEL. In two of eight cases, a few bizarre astrocytes were faintly labelled. Histologically normal tissues surrounding the PML lesions and the negative control cases showed no unequivocal labeling with all markers. We confirmed the results of previous studies suggesting overexpression and/or stabilization of p53 following overexpression of PCNA in glial cells in the PML brain. We conclude that apoptosis does not seem to be an important mechanism for glial cell elimination in the PML brain. In addition, uniform expression of the virus antigen, tumor suppressor gene products and proliferation markers was associated with little variance in the morphology of PML cells and variable expression of these markers was associated with variable morphology of bizarre astrocytes in the PML brain.
A comparison of histological and immunohistochemical methods for quantifying the pathological lesions of Pick's disease
Authors: Armstrong RA , Cairns NJ , Lantos PL
Published: May 2007

Counts of Pick bodies (PB), Pick cells (PC), senile plaques (SP) and neurofibrillary tangles (NFT) were made in the frontal and temporal cortex from patients with Pick's disease (PD). Lesions were stained histologically with hematoxylin and eosin (HE) and the Bielschowsky silver impregnation method and labeled immunohistochemically with antibodies raised to ubiquitin and tau. The greatest numbers of PB were revealed by immunohistochemistry. Counts of PB revealed by ubiquitin and tau were highly positively correlated which suggested that the two antibodies recognized virtually identical populations of PB. The greatest numbers of PC were revealed by HE followed by the anti‐ubiquitin antibody. However, the correlation between counts was poor, suggesting that HE and ubiquitin revealed different populations of PC. The greatest numbers of SP and NFT were revealed by the Bielschowsky method indicating the presence of Alzheimer‐type lesions not revealed by the immunohistochemistry. In addition, more NFT were revealed by the anti‐ubiquitin compared with the anti‐tau antibody. The data suggested that in PD: (i) the anti‐ubiquitin and anti‐tau antibodies were equally effective at labeling PB; (ii) both HE and anti‐ubiquitin should be used to quantitate PC; and (iii) the Bielschowsky method should be used to quantitate SP and NFT.
Expression of the candidate invasion suppressor gene, nm23, in human brain tumors
Authors: Martin Kimberly , King Andrew , O'Neill Kevin , Kandanearatchi Apsara , Liyanage Krishanthi , Pilkington Geoffrey J
Published: May 2007

The nm23 genes encode a family of multifunctional proteins with well‐documented enzymatic and DNA‐binding functions. There are five isoforms of nm23 of which two, nm23‐H1 and nm23‐H2 have been widely studied within the context of metastasis suppression in a large variety of human cancers. However, the role of nm23 in mediating the invasive behavior of central nervous system neoplasms remains to be clarified. In the present study, we provide evidence that nm23 may suppress the invasive phenotype in primary human brain tumors.
Spinal intramedullary cysticercosis: A case report
Authors: Escobar Alfonso , Herrera Maria Petra , Escobar William , Vega Rosalba
Published: May 2007

The parasitic infection of the central nervous system due to Cystiacercus cellulosae usually affects the intracranial structures. The spinal form of neurocysticercosis is uncommon, anatomically confirmed cases range from 0.77 to % among all cases of neurocysticercosis. Even fewer cass appear as spinal intramedullary cysticercosis (SIC); no than 49 confirmed cases have been reported in the literature. One case of SIC is reported here. The patient showed both motor and sensory symptoms that improved after One year later he is working again and only pperreflexia has been detected. Although the magnetic resonance imaging studies showed a cystic intramedullary lesion it was considered to be spinal glioma; only after histologic Study was the exact diagnosis made. The clinical symptomatology in these cases is due to compression of descending and ascending spinal tracts; the clinical diagnosis may be suspected in countries where cysticercosis is endemic. Modern neuroimaging techniques provide higher possibilities of accurate diagnosis; however, it can only be established with certainty by histologic study of the surgical specimen.
Apoptosis in metastatic carcinoma of the central nervous system
Authors: Sawada Tatsuo , Takekawa Yoshinori , Sakurai Isamu , Kobayashi Makio
Published: May 2007

High apoptotic indices have been described in pseud‐opalisading areas of glioblastoma multiforme (astrocytoma grade 4). In order to explore further the role of apoptosis in regulating the proliferation in central nervous system (CNS) tumors, we used TdT‐mediated dUTP‐nick endlabeling (TUNEL) methods to compare the frequency and distribution of apoptotic cells in 32 cases of metastatic carcinoma and 54 cases of primary diffuse astrocytomas. Frequencies of apoptotic cells and Bcl‐2 positive cells in metastatic carcinoma were low compared with those observed in high‐grade diffuse astrocytomas and did not correlate with the expression of the p53 protein. These findings suggest that apoptosis does not have a major role in regulating proliferation in metastatic carcinoma of the CNS.
Ret expression in the central nervous system
Authors: Hagihara Naoshi , Fukuyama Kouzou , Tabuchi Kazuo
Published: May 2007

The ret proto‐oncogene product (Ret) has been shown to be one of the glial cell line‐derived neurotrophic factor (GDNF) receptors in dopaminergic, norepinephric and motor neurons. We immunohistochemically examined the expression of Ret in the human central nervous system (CNS). The distribution of Ret was generally identical to that of myclin as stained using the Klüver‐Barrera method. We further investigated the expression of Ret in human fetal brains (19, 29 and 39 weeks gestation) and various brain tumors. The Ret positivity was observed to be associated with the myelin sheath of the cerebral white matter in 29‐and 39‐week‐old fetal brains. Ret is known to be expressed in neural crest‐derived cells. We could immunohistochemically confirm the Ret expression in the pheochromocytomas and neuroblastomas of retroperitoneal space. As for the brain tumors, no Ret expression was observed in glioblastomas, oligodendrogliomas, and schwannomas examined, although the glial cells surrounding the tumor and the pre‐existing myelin sheath revealed positivity for Ret. In the CNS, Ret expression appears to be closely associated with the myelin sheath; therefore, Ret immunostaining may be useful in ascertaining the demyelinating lesions in the CNS.