bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic factors for recurrence in patients with FIGO stage I and II, intermediate or high risk endometrial cancer
Authors: ZUSTERZEEL P.L.M. , BEKKERS R.L.M. , HENDRIKS J.C.M. , NEESHAM D.N. , ROME R.M. , QUINN M.A.
Published: January 2008

Background. The aim of this study was to determine predictors for loco‐regional or distant recurrence of disease in a subgroup of intermediate or high risk stage I and II endometrial cancer. Methods. A retrospective analysis of 295 patients with histopathological stage I and II, intermediate or high risk endometrial cancer is reported. The following factors were studied: stage, grade, age, histologic diagnosis, lymphadenectomy, lymphovascular space invasion, and adjuvant radiotherapy. The Log‐Rank test was used for statistical analyses and the Kaplan–Meyer method was used for time‐to‐event analysis. Multivariate analysis was also performed. Results. Thirty‐four (11.5%) patients developed a recurrence; 20 (59%) developed loco‐regional recurrence, and 14 (41%) developed distant recurrence. In 20 women (59%), recurrence appeared within 3 years of surgery, and the actuarial survival at 3 years after recurrence was 29%. Multivariate analysis showed that for recurrence, age >60 years was a significant unfavourable prognostic factor (p < 0.05). Conclusions. We found low rates of recurrence in patients with early stage intermediate or high risk endometrial cancer. Only age was identified as an independent significant predictor for recurrence.
Pulmonary arterial remodeling induced by a Th2 immune response
Authors: Daley Eleen , Emson Claire , Guignabert Christophe , de Waal Malefyt Rene , Louten Jennifer , Kurup Viswanath P. , Hogaboam Cory , Taraseviciene-Stewart Laimute , Voelkel Norbert F. , Rabinovitch Marlene , Grunig Ekkehard , Grunig Gabriele
Published: January 2008

Pulmonary arterial remodeling characterized by increased vascular smooth muscle density is a common lesion seen in pulmonary arterial hypertension (PAH), a deadly condition. Clinical correlation studies have suggested an immune pathogenesis of pulmonary arterial remodeling, but experimental proof has been lacking. We show that immunization and prolonged intermittent challenge via the airways with either of two different soluble antigens induced severe muscularization in small- to medium-sized pulmonary arteries. Depletion of CD4+ T cells, antigen-specific T helper type 2 (Th2) response, or the pathogenic Th2 cytokine interleukin 13 significantly ameliorated pulmonary arterial muscularization. The severity of pulmonary arterial muscularization was associated with increased numbers of epithelial cells and macrophages that expressed a smooth muscle cell mitogen, resistin-like molecule α, but surprisingly, there was no correlation with pulmonary hypertension. Our data are the first to provide experimental proof that the adaptive immune response to a soluble antigen is sufficient to cause severe pulmonary arterial muscularization, and support the clinical observations in pediatric patients and in companion animals that muscularization represents one of several injurious events to the pulmonary artery that may collectively contribute to PAH.
Inhibition of histamine-mediated signaling confers significant protection against severe malaria in mouse models of disease
Authors: Beghdadi Walid , Porcherie Adeline , Schneider Bradley S. , Dubayle David , Peronet Roger , Huerre Michel , Watanabe Takeshi , Ohtsu Hiroshi , Louis Jacques , Mécheri Salaheddine
Published: January 2008

From the inoculation of Plasmodium sporozoites via Anopheles mosquito bites to the development of blood-stage parasites, a hallmark of the host response is an inflammatory reaction characterized by elevated histamine levels in the serum and tissues. Given the proinflammatory and immunosuppressive activities associated with histamine, we postulated that this vasoactive amine participates in malaria pathogenesis. Combined genetic and pharmacologic approaches demonstrated that histamine binding to H1R and H2R but not H3R and H4R increases the susceptibility of mice to infection with Plasmodium. To further understand the role of histamine in malaria pathogenesis, we used histidine decarboxylase–deficient (HDC−/−) mice, which are free of histamine. HDC−/− mice were highly resistant to severe malaria whether infected by mosquito bites or via injection of infected erythrocytes. HDC−/− mice displayed resistance to two lethal strains: Plasmodium berghei (Pb) ANKA, which triggers cerebral malaria (CM), and Pb NK65, which causes death without neurological symptoms. The resistance of HDC−/− mice to CM was associated with preserved blood–brain barrier integrity, the absence of infected erythrocyte aggregation in the brain vessels, and a lack of sequestration of CD4 and CD8 T cells. We demonstrate that histamine-mediated signaling contributes to malaria pathogenesis. Understanding the basis for these biological effects of histamine during infection may lead to novel therapeutic strategies to alleviate the severity of malaria.
Invariant subspaces for Banach space operators with an annular spectral set
Authors: Yavuz Onur
Published: January 2008

Consider an annulus

Ω
=
{
z
∈

C

:

r

0

>

|

z

|

>
1
}

\Omega =\{z\in \mathbb {C}:r_ {0}>|z|>1\}

for some

0
>

r

0

>
1

0>r_{0}>1

, and let

T
T

be a bounded invertible linear operator on a Banach space

X
X

whose spectrum contains

∂
Ω

\partial \Omega

. Assume there exists a constant

K
>
0

K>0

such that
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="double-vertical-bar p left-parenthesis upper T right-parenthesis double-vertical-bar less-than-or-equal-to upper K sup left-brace right-brace colon vertical-bar vertical-bar of pp left-parenthesis right-parenthesis lamda colon less-than-or-equal-to less-than-or-equal-to vertical-bar vertical-bar lamda 1">

‖
p
(
T
)
‖
 
≤
 
K
sup
{

|

p
(
λ
)

|

:

|

λ

|

≤
1
}

\|p(T)\|~\leq ~ K \sup \{|p(\lambda )|:|\lambda |\leq 1\}

and
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="double-vertical-bar p left-parenthesis r 0 upper T Superscript negative 1 Baseline right-parenthesis double-vertical-bar less-than-or-equal-to upper K sup left-brace right-brace colon vertical-bar vertical-bar of pp left-parenthesis right-parenthesis lamda colon less-than-or-equal-to less-than-or-equal-to vertical-bar vertical-bar lamda 1">

‖
p
(

r
0

T

−
1

)
‖
≤
K
sup
{

|

p
(
λ
)

|

:

|

λ

|

≤
1
}

\|p(r_0T^{-1})\|\leq K \sup \{|p(\lambda )|:|\lambda |\leq 1\}

for all polynomials

p
p

. Then there exists a nontrivial common invariant subspace for

T

∗

T^{*}

and

T

∗

−
1

{T^{*}}^{-1}

.
Supercharacters and superclasses for algebra groups
Authors: Diaconis Persi , Isaacs I.
Published: January 2008

We study certain sums of irreducible characters and compatible unions of conjugacy classes in finite algebra groups. These groups generalize the unimodular upper triangular groups over a finite field, and the supercharacter theory we develop extends results of Carlos André and Ning Yan that were originally proved in the upper triangular case. This theory sometimes allows explicit computations in situations where it would be impractical to work with the full character table. We discuss connections with the Kirillov orbit method and with Gelfand pairs, and we give conditions for a supercharacter or a superclass to be an ordinary irreducible character or conjugacy class, respectively. We also show that products of supercharacters are positive integer combinations of supercharacters.
Rational irreducible characters and rational conjugacy classes in finite groups
Authors: Navarro Gabriel , Tiep Pham
Published: January 2008

We prove that a finite group

G
G

has two rational-valued irreducible characters if and only if it has two rational conjugacy classes, and determine the structure of any such group. Along the way we also prove a conjecture of Gow stating that any finite group of even order has a non-trivial rational-valued irreducible character of odd degree.
The Brown-Peterson cohomology of the classifying spaces of the projective unitary groups 𝑃𝑈(𝑝) and exceptional Lie groups
Authors: Kameko Masaki , Yagita Nobuaki
Published: January 2008

For a fixed prime

p
p

, we compute the Brown-Peterson cohomologies of classifying spaces of

P
U
(
p
)

PU(p)

and exceptional Lie groups by using the Adams spectral sequence. In particular, we see that

B

P
∗

(
B
P
U
(
p
)
)

BP^*(BPU(p))

and

K
(
n

)
∗

(
B
P
U
(
p
)
)

K(n)^*(BPU(p))

are even dimensionally generated.
Positive solutions and multiple solutions at non-resonance, resonance and near resonance for hemivariational inequalities with 𝑝-Laplacian
Authors: Motreanu D. , Motreanu V. , Papageorgiou N.
Published: January 2008

In this paper we study eigenvalue problems for hemivariational inequalities driven by thepp-Laplacian differential operator. We prove the existence of positive smooth solutions for both non-resonant and resonant problems at the principal eigenvalue of the negativepp-Laplacian with homogeneous Dirichlet boundary condition. We also examine problems which are near resonance both from the left and from the right of the principal eigenvalue. For nearly resonant from the right problems we also prove a multiplicity result.
Universal Toda brackets of ring spectra
Authors: Sagave Steffen
Published: January 2008

We construct and examine the universal Toda bracket of a highly structured ring spectrum

R
R

. This invariant of

R
R

is a cohomology class in the Mac Lane cohomology of the graded ring of homotopy groups of

R
R

which carries information about

R
R

and the category of

R
R

-module spectra. It determines for example all triple Toda brackets of

R
R

and the first obstruction to realizing a module over the homotopy groups of

R
R

by an

R
R

-module spectrum. For periodic ring spectra, we study the corresponding theory of higher universal Toda brackets. The real and complex

K
K

-theory spectra serve as our main examples.
Phyutility: a phyloinformatics tool for trees, alignments and molecular data
Authors: Smith Stephen A. , Dunn Casey W.
Published: January 2008

Summary: Phyutility provides a set of phyloinformatics tools for summarizing and manipulating phylogenetic trees, manipulating molecular data and retrieving data from NCBI. Its simple command-line interface allows for easy integration into scripted analyses, and is able to handle large datasets with an integrated database.

Availability: Phyutility, including source code, documentation, examples, and executables, is available at http://code.google.com/p/phyutility

Contact:  stephen.smith@yale.edu
Utility library for structural bioinformatics
Authors: Gront Dominik , Kolinski Andrzej
Published: January 2008

Summary: In this Note we present a new software library for structural bioinformatics. The library contains programs, computing sequence- and profile-based alignments and a variety of structural calculations with user-friendly handling of various data formats. The software organization is very flexible. Algorithms are written in Java language and may be used by Java programs. Moreover the modules can be accessed from Jython (Python scripting language implemented in Java) scripts. Finally, the new version of BioShell delivers several utility programs that can do typical bioinformatics task from a command-line level.

Availability The software is available for download free of charge from its website: http://bioshell.chem.uw.edu.pl. This website provides also numerous examples, code snippets and API documentation.

Contact:  dgront@chem.uw.edu.pl
A discrete view on fold space
Authors: Sippl Manfred J. , Suhrer Stefan J. , Gruber Markus , Wiederstein Markus
Published: January 2008

Summary: The database of known protein structures contains an overwhelming number of structural similarities that frequently point to intriguing biological relationships. The similarities are often difficult to spot, and once detected their comprehension needs proper visualization. Here we introduce the new concept of a Fold Space Navigator, a user interface enabling the efficient navigation through fold space and the instantaneous visualization of pairwise structure similarities.

Availability: The Fold Space Navigator is accessible as a public web service at http://services.came.sbg.ac.at

Contact:  sippl@came.sbg.ac.at
TaxonGap: a visualization tool for intra- and inter-species variation among individual biomarkers
Authors: Slabbinck B. , Dawyndt P. , Martens M. , De Vos P. , De Baets B.
Published: January 2008

Summary: Selection of optimal biomarkers for the identification of different operational taxonomic units (OTUs) may be a hard and tedious task, especially when phylogenetic trees for multiple genes need to be compared. With TaxonGap we present a novel and easy-to-handle software tool that allows visual comparison of the discriminative power of multiple biomarkers for a set of OTUs. The compact graphical output allows for easy comparison and selection of individual biomarkers.

Availability: Graphical User Interface; Executable JAVA archive file, source code, supplementary information and sample files can be downloaded from the website: http://www.kermit.ugent.be/taxongap

Contact:  Bram.Slabbinck@UGent.be
Evidence from survey data for regional variability in cod dynamics in the North Sea and West of Scotland
Authors: Holmes Steven J. , Wright Peter J. , Fryer Robert J.
Published: January 2008

Holmes, S. J., Wright, P. J., and Fryer, R. J. 2008. Evidence from survey data for regional variability in cod dynamics in the North Sea and West of Scotland. – ICES Journal of Marine Science, 65: 206–215. Although cod (Gadus morhua) in the North Sea and ICES Division VIa are assessed as single units, recent research suggests that the stocks consist of reproductively isolated subpopulations within a metapopulation. We investigate whether temporal trends in stock indicators are asynchronous across subpopulations, which would support the metapopulation hypothesis. First quarter trawl survey data for the years 1983–2005 were aggregated into putative areas of high spawner fidelity (three in VIa, seven in the North Sea) to obtain indices of spawning–stock biomass (SSB) and recruitment (numbers-at-age 1). Asynchrony was investigated by fitting a smoother to the data for each of the ten spawning areas and testing whether the smoothers were parallel. Trends in SSB differed between spawning areas in both VIa and the North Sea. In VIa, SSB collapsed in the most southwesterly area, but remained more constant elsewhere. In the North Sea, there was a general decline in SSB, but areas thought to contain resident inshore populations showed more rapid declines than those in adjacent offshore areas. Recruitment results offered less support for a metapopulation, although recruitment in the southern North Sea declined rapidly before any trend was seen for the North Sea as a whole.
Tailoring systematic reviews to meet critical priorities in maternal health in the intrapartum period
Authors: Viswanathan Meera
Published: January 2008

Health care practitioners and researchers commonly call for greater reliance on evidence as a means to achieve improvement in quality of care. Systematic reviews provide a means to accelerate the use of evidence‐based clinical interventions and public health practices. The extent to which these time‐ and resource‐intensive systematic reviews currently address critical maternal health priorities in the intrapartum period is unclear. This analysis summarises key maternal health and research priorities, maps these priorities to existing reviews, identifies gaps in the literature that can be addressed with systematic reviews, and highlights key methodological concerns in conducting systematic reviews. The analysis draws on published data on maternal morbidities and an overview of 108 systematic reviews in Medline in the past 5 years using the MeSH terms ‘Delivery, Obstetric,’ to draw the links between health priorities, research priorities, existing evidence and missing evidence.

Key causes of morbidity during labour and delivery in the United States include haemorrhage, pre‐eclampsia and eclampsia, obstetric trauma and infection. Analyses of maternal morbidity and mortality suggest that key concerns include racial and ethnic disparities in health outcomes and the prevention of adverse events. Systematic reviews, however, generally tend to focus on the reduction of harms associated with interventions, are frequently limited to randomised designs, and do not address issues of health disparities. The results suggest that advances in evidence‐based care in maternal health require that systematic reviews address issues of prevention of adverse events, include a larger variety of study designs when necessary and pay closer attention to health disparities.
Motivating authors to update systematic reviews: practical strategies from a behavioural science perspective
Authors: Ervin Ann‐Margret
Published: January 2008

Systematic reviews are used by clinicians, policy makers and consumers of health care, and should provide up‐to‐date evidence for clinical decision making. Motivating systematic review authors to update reviews is a challenge, and despite resources such as methodologists and statisticians, many reviews are not updated in a timely manner. Conflicting clinical responsibilities, lack of funding or other essential resources, and waning interest in the review topic are potential barriers to updating. Illustrations of survey questions to elicit updating attitudes and beliefs, and conditions that make updating easier or more difficult within the framework of the Theory of Planned Behaviour, are presented. These surveys may be used to tailor interventions to assist authors with difficulties and may ultimately increase the rate of updates in the published literature.
Recommendations to increase the impact of maternal and childbirth health systematic reviews in the Americas
Authors: Jacquérioz Frédérique A , Belizán José M. , Buekens Pierre
Published: January 2008

This paper summarises the discussions and the recommendations formulated during a meeting in March 2007 on the challenges and strategies to increase the impact of maternal and childbirth health systematic reviews in the Americas. The discussions addressed three specific themes: (1) performing systematic reviews (2) updating existing reviews, and (3) diffusing and implementing evidence into practice. Practical recommendations were devised for each theme in small group discussions.
MASS‐VACCINATION PROGRAMMES AND THE VALUE OF RESPECT FOR AUTONOMY
Authors: ASVELD LOTTE
Published: January 2008

Respect for autonomy is problematic in relation to public health programmes such as vaccination, as the success of such programmes depends on widespread compliance. European countries have different policies for dealing with objectors to vaccination programmes. In some countries compliance is compulsory, while in others objectors are exempted or allowed to enter the programme under specific conditions.

In this paper I argue that the objectors should not be treated as a homogenous group as is done in the above‐mentioned policies. Objectors have different arguments for not participating in vaccination programmes. Considering the value of respect for autonomy, some but not all of these arguments need to be accommodated by authorities.

The concept of ‘narrative autonomy’ provides criteria to distinguish between tenable and untenable claims to the right to refuse vaccination. Narrative autonomy understands autonomy as essentially linked to identity, as this provides the moral framework with which we assess our first‐order preferences.

The above‐mentioned concept of autonomy is derived from the concept of narrative identity as described by Marya Schechtman. She suggests that the application of the Articulation Constraint and the Reality Constraint enables us to establish the validity of personal narratives. Additionally, form and content features of identity, as proposed by Anthony Laden, will be used as criteria to establish the compatibility of the defectors’ arguments with shared scientific and political values. Such compatibility is essential to accommodate respect for autonomy in the context of public health.
The Politics of Legal Representation: The Influence of Local Politics on the Behavior of Poverty Lawyers
Authors: KESSLER MARK
Published: January 2008

This article explores the influence of local groups on the strategies employed by poverty lawyers in representing clients. Data collected from one suburban legal services program suggest that despite attitudinal predispositions to initiate law reform litigation, poverty lawyers are constrained in their use of social reform strategies by local organizations opposed to such activity. I argue that politics inevitably affect poverty lawyer behavior due to the nature of legal services work and programmatic features of the national Legal Services Corporation. I assess the implications of these findings for federal control of local programs.
The Justice Model in the Juvenile Justice System: Washington State's Experience
Authors: CASTELLANO THOMAS C.
Published: January 2008

In 1977, the Washington State Legislature enacted radical modifications of its juvenile justice code. Explicitly abandoning the parens patriae philosophy of the juvenile justice system, a “justice” philosophy was adopted. Provisions of the law include a determinate sentencing structure, the divestiture of status offenses, greater due process rights for juveniles, and a formalized diversion process which emphasizes accountability rather than treatment. This paper brings together the available research on the implementation of the law to assess how the introduction of a justice approach has influenced equality, fairness, and punishment levels in Washington State's juvenile justice system.
Ethical Disparities: Challenges Encountered by Multidisciplinary Providers in Fulfilling Ethical Standards in the Care of Rural and Minority People
Authors: Roberts Laura Weiss , Johnson Mark E. , Brems Christiane , Warner Teddy D.
Published: January 2008

ABSTRACT: 
Context: Health care disparities are well documented for people living in rural areas and for people who are members of ethnic minorities. Purpose: Our goal was to determine whether providers report greater difficulty in providing care for rural than urban residents and for ethnic minorities than patients/clients in general in 4 practice areas of ethical relevance: attaining treatment adherence, assuring confidentiality, establishing therapeutic alliance, and engaging in informed consent processes. Methods: We received survey responses from 1,558 multidisciplinary medical and behavioral providers across rural and non‐rural areas of New Mexico and Alaska in 2004 to assess a wide range of issues in providing health care. Findings: Providers reported some difficulties in fulfilling various ethical practices for all types of patients, but not more difficulty when caring for minority compared to nonminority patients/clients. However, they do report more frequent additional problems related to the practice issues of treatment adherence, therapeutic alliance, informed consent, and confidentiality with minority patients than others. Difficulties and more frequent additional problems are greater for providers in rural than in non‐rural areas. Results generalize across both Alaska and New Mexico with few differences. Conclusions: We obtained evidence for disparity in care for patients/ clients who were minority group members, and clear evidence of disparity for people residing in rural compared to non‐rural areas of 2 states with large rural areas.
Small mammal diversity and habitat requirements in the Kahuzi‐Biega National Park and surrounding areas, eastern Democratic Republic of Congo
Authors: KALEME Prince K. , BATES John , PETERANS Julian Kerbis , JACQUES Mwanga M. , NDARA Benjamin R.
Published: January 2008

We conducted a study on diversity and habitat requirements of small mammals in the western part of the Albertine Rift, eastern Democratic Republic of Congo. The work aimed at providing a more complete list of species recorded to date and their habitat requirements to aid conservation efforts in the region. Trapping was conducted using Museum special, Victor traps, Sherman live traps and pitfall traps in four different habitats. A total of 57 species was recorded. Plantations and open habitats harbored the same species. In the forested areas we recorded 30 species which are not tolerant to disturbance. Eighteen species are Albertine Rift endemics. One species (Lophuromys cinereus), which is vulnerable and data deficient, has been recorded only in swamp. This study has recorded more species than the previous studies, some of which have not been reported in earlier studies. Differences between this and earlier studies are attributed to methods and the areas sampled. Some of the habitats sampled by previous workers have not been assessed. More research is needed, especially in swamps in mountain areas and in deep forests inhabited by species not present at lower altitudes.
Progress toward the Isolation and Characterization of the Genes Causing Neurofibromatosis
Authors: Menon Anil G. , Gusella James F. , Seizinger Bernd R.
Published: January 2008

Neurofibromatosis 1 and neurofibromatosis 2 are clinically distinct autosomal dominant disorders that affect an estimated 1.5 million individuals throughout the world. The genetic defect in each disorder has been mapped to different chromosomes, NF1 to chromosome 17 and NF2 to chromosome 22. Progress towards the cloning of the NF1 gene has proceeded rapidly. The NF1 locus was bracketed using genetic linkage analysis on NF1 affected pedigrees. Physical mapping methods were then used to precisely map the translocation breakpoints in each of two NF1 affected individuals who harbored constitutional chromosomal translocations in the putative NF1 region of chromosome 17. The region of DNA located between the two translocations has been cloned in cosmids and yeast artificial chromosomes and a number of RNA coding sequences have been identified. The identification of the NF1 gene will depend on finding mutations in the DNA of affected individuals. In the case of NF2, progress seems to have been less rapid, in part due to the lower availiability of NF2 affected pedigrees. The genetic defect has been mapped to the long arm of chromosome 22 by studies of chromosomal loss in the tumours associated with this disease. Subsequent genetic mapping has confirmed this location. Flanking DNA markers for the NF2 locus have been identified. The region of DNA between these markers is in the order of 5–10 Mb. The identification of chromosomal aberrations in patients with NF2 that involve chromosome 22 will play an important role in the identification of the NF2 gene in much the same way as they have in NF1.
Bovine Spongiform Encephalopathy: A Neuropathological Perspective
Authors: Wells Gerald A. H. , Wilesmith John W. , McGill Iain S.
Published: January 2008

The occurrence of bovine spongiform encephalopathy (BSE), recognition that it is a new scrapie‐like disease epidemic in domestic cattle in the United Kingdom and concern of a remote zoonotic potential has, in four years, produced a plethora of documented information. While much of this information has been communicated outwith the scientific literature, this review attempts to summarise, from a neuropathological viewpoint, the main findings to emerge. The initial studies established the nosological homology of BSE with the subacute spongiform encephalopathies or “prion” diseases of animals and man. Epidemiological data are consistent with an extended common source epidemic originating from an abrupt change, commencing in 1981‐82, in the exposure of domestic cattle to a scrapie‐like agent in meat and bone meal incorporated into commercial animal feedstuffs. It is currently proposed that the method of production of meat and bone meal has contributed vital factors to the change in exposure. Invariability of the distribution pattern of vacuolar pathology in the natural disease and on primary transmission to cattle suggests a uniformity of the pathogenesis of BSE. Studies in mice suggest uniformity also of the biological properties of different BSE isolates but indicate that the properties differ from those of sheep scrapie isolates. Human health risks, although perceived to be negligible, have been addressed by various strategies including statutory measures and long term monitoring.
Mesenchymal, IMon‐Meningothelial Tumors of the Central Nervous System
Authors: Jellinger Kurt , Paulus Werner
Published: January 2008

The spectrum of non‐meningothelial mesenchymal tumors that may arise within the central nervous system is presented, based on the current classification of soft tissue tumors. Among malignant types, hemangiopericytoma, rhabdomyosarcoma, mesenchymal chondrosarcoma, and malignant fibrous histiocytoma are the most frequent ones. Rare tumor entities are mentioned. As in soft tissue sarcomas, diagnosis is mainly based on light and electron microscopy, while immunohistochemistry can improve accuracy of diagnosis.
Expression of Adhesion Molecules and Histocompatibility Antigens at the Blood‐Brain Barrier
Authors: Lassmann H. , Rössler K. , Zimprich F. , Vass K.
Published: January 2008

The migration of inflammatory cells through the blood‐brain barrier in health and disease involves complex interactions between hematogenous cells, endothelial cells, the basement membrane and the perivascular glia limitans. Recent evidence is presented, suggesting that part of these interactions involve antigen independent mechanisms, mediated by cellular adhesion molecules. The accessibility of endothelial adhesion molecules in the intact blood‐brain barrier is lower compared to vessels in other organs. This may account for the low traffic of hematogenous cells through the normal blood‐brain barrier. However, in inflammatory conditions the expression of endothelial adhesion molecules is upregulated, which may lead to recruitment of inflammatory cells into the lesions. Antigen specific activation of T‐ceiis at the blood‐brain barrier apparently takes place mainly at perivascular monocytes and microglia cells. In severe inflammatory lesions, however, astrocytes may be additionally involved in antigen presentation.
Neuropathology in the Third Reich
Authors: Peiffer Jurgen
Published: January 2008

In July 1990, the Eberhard‐Karls University of Tübingen held a memorial ceremony on the occasion of the erection of a stone in burial ground X of the City Cemetery, to commemorate those victims of Nazi terror whose bodies were used during the years 1933–1945 for medical research and student teaching. The following is a transcript of the memorial speech given by Jürgen Peiffer, Emeritus Professor of Neuropathology.
MEETING REPORT
Authors: Olsson Yngve
Published: January 2008

XI International Congress of Neuropathology, Kyoto, Japan, September 2 ‐ 8, 1990
AIDS Dementia Complex and HIV‐1 Infection: A View From the Clinic
Authors: Price Richard W. , Sidtis John J. , Brew Bruce J.
Published: January 2008

The AIDS dementia complex (ADC) is a clinical syndrome which characteristically presents as a “subcortical dementia” with cognitive, motor and behavioral changes. While the pathogenesis remains puzzling in a number of critical aspects, ADC likely relates in a fundamental way to HIV‐1, itself, rather than to a secondary, opportunistic condition. This review focuses on some of the clinical information which bears on the pathogenesis of this syndrome and its relation to HIV‐1 infection. This information derives from studies of the clinical character of ADC, its epidemiology and natural history, cerebrospinal fluid analysis, neuroimaging results, clinical correlates of pathological findings and its response to antiviral therapy.
Neuropathology of Human Immunodeficiency Virus Infection
Authors: Budka Herbert
Published: January 2008

Neuropathology has defined novel HIV‐specific diseases at tissue level: HIV encephalitis and HIV leukoencephalopathy. Both occur usually in the later stages of the AIDS infection and consistently demonstrate large amounts of HIV products. In contrast to this HIV‐specific neuropathology, HlV‐asso‐ciated neuropathology features unspecific syndromes with disputed relation to HIV infection: myelin pallor, vacuolar myelopathy, vacuolar leukoencephalopathy, lymphocytic meningitis, and diffuse poliodystrophy. All types of neuropathology may contribute to clinical manifestation according to severity, extent, and distribution of lesions, but clinico‐pathologic correlation may be poor in the individual case. Neuropathologic and other data suggest two major pathogenetic pathways of HIV‐associated CNS damage: First, systemic and local increase of the virus load leads to HIV encephalitis or HIV leukoencephalopathy; this is corroborated by prominent HIV production within such lesions. Second, neuronotoxicity by HIV proteins or factors secreted from infected cells is supported by histological changes of diffuse poliodystrophy and by morphometric loss of frontocortical neurons.
Neurobiology of Simian and Feline Immunodeficiency Virus Infections
Authors: Lackner Andrew A. , Dandekar Satya , Gardner Murray B.
Published: January 2008

Experimental and clinical evidence indicates that all lentiviruses of animals and humans are neurotropic and potentially neurovirulent. The prototypic animal lentiviruses, visna virus in sheep and caprine arthritis encephalitis virus in goats have been known for decades to induce neurologic disease. More recently, infection of the brain with the human immunodeficiency virus (HIV) has been linked to an associated encephalopathy and cognitive/motor complex. While the visna virus and caprine arthritis encephalitis virus are important models of neurologic disease they are not optimal for the study of HIV encephalitis because immune deficiency is only a minor component of the disease they induce. By contrast, the recently isolated lentiviruses from monkeys and cats, the simian and feline immunodeficiency viruses (SIV and FIV respectively), are profoundly immunosuppressive as well as neurotropic. SIV infection of the central nervous system of macaques now provides the best animal model for HIV infection of the human brain due to the close evolutionary relationship between monkeys and man, the genetic relatedness of their respective lentiviruses, and the similarities in the neuropathology. This chapter will compare and contrast the neurobiology of SIV and FIV with HIV.
Demonstration of Amyloid Deposits and Neurofibrillary Changes in Whole Brain Sections
Authors: Braak Heiko , Braak Eva
Published: January 2008

Selective and sensitive silver staining of extracellular amyloid deposits and intraneuronal neurofibrillary changes can be applied to 50–150 μ.m thick polyethylene glycol sections and/or 5–15 μ.m thick paraffin sections. The silver techniques take advantage of physical development of the nucleation sites thus permitting tight control of the entire procedure. Both techniques can be applied to routinely fixed autopsy material. They do not require particular skills and considerably facilitate processing of large numbers of sections through entire hemispheres of the human brain.
Disorders Associated with Depletion of Mitochondrial DNA
Authors: Ricci Enzo , Moraes Carlos T. , Servidei Serenella , Tonali Pietro , Bonilla Eduardo , DiMauro Salvatore
Published: January 2008

Quantitative defects of mtDNA have been recently described in patients with fatal mitochondrial disease of early infancy or mitochondrial myopathy of childhood. There was variable tissue expression and depletion of up to 98% of mtDNA in affected tissues. Pedigree analysis was compatible with mendelian inheritance, suggesting faulty communication between nuclear and mitochondrial genomes, but the primary molecular lesion is unknown. In muscle, morphological studies allowed to correlate mtDNA depletion, absence of mtDNA‐encoded peptides, mitochondrial proliferation, and loss of cytochrome c oxidase (COX) activity in individual fibers.
Mitochondria and Ageing
Authors: Müller‐Höcker Josef
Published: January 2008

This work reviews the role of mitochondria in the ageing process and summarizes pathomorphological biochemical and molecular genetic data. The pathophysiological mechanisms underlying the phenomenon of ageing are only partly understood. There is, however, increasing evidence that mitochondria are essentially involved. In various tissues of various species a decline in the respiratory chain capacity is seen with ageing. Enzyme histochemistry of cytochrome c oxidase (complex IV of the respiratory chain) has revealed an age‐related increase of randomly distributed defective fibres/cells in the skeletal and heart muscle the random pattern probably indicating cellular heterogeneity of the ageing process. Observed deletions of mitochondrial DNA during ageing may represent one causative factor. Similar to primary mitochondrial myopathies point mutations and depletion of the mtDNA are probably also involved. There is some evidence that damage of the mitochondrial genome and of other mitochondrial structures might be due to increased oxygen radical production during ageing. The role of nuclear influences on the degeneration of mitochondrial function remains, however, also to be determined. Nevertheless, the decline of respiratory chain function with ageing represents an important factor for the decline of functional organ reserve capacity in senescence.
Mitochondrial Encephalomyopathies: Defects of Nuclear DNA
Authors: Shanske Sara
Published: January 2008

The term “mitochondrial diseases” encompasses a heterogeneous group of disorders in which a primary mitochondrial dysfunction is suspected or proven by morphologic, genetic, or biochemical criteria (1,2). Clinically, these progressive disorders usually affect muscle, either alone (mitochondrial myopathies) or in combination with other systems, most often brain (encephalomyopathies). Mitochondria are unique among intracellular organelles in that mitochondrial proteins are encoded by two genomes, nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). The vast majority of mitochondrial proteins are encoded by the nuclear genome, whereas mtDNA (a circular, double stranded 16.5 kb molecule) encodes only 13 polypeptides, all of them subunits of respiratory chain complexes. In addition to structural genes, mtDNA also codes for 22 transfer RNAs and two ribosomal RNAs. Our understanding of mitochondrial diseases has grown at an impressive rate in the past few years, and most of the progress has been in the area of mtDNA genetics, where several mtDNA mutations have been associated with specific diseases (reviewed in this issue by Zeviani et al.). In comparison, our understanding of mitochondrial disorders due to nDNA lesions has lagged behind and, to date, molecular defects of nuclear genes have been documented in only a few patients. We will review which alterations in the nuclear genome can cause mitochondrial disorders and which criteria are useful in identifying such mutations. While several examples will be provided, this is not intended as a complete review of the subject.
Effect of Cerebral Blood Flow and Cerebrovascular Autoregulation on the Distribution, Type and Extent of Cerebral Injury
Authors: Greisen Gorm
Published: January 2008

Global cerebral blood flow (GCBF) is low in the human neonate compared to the adult. It is even lower in mechanically ventilated, preterm infants: 10–12 ml/100 g/minute, a level associated with brain infarction in adults. The reactivity, however, of global CBF to changes in cerebral metabolism, PaCO2, and arterial blood pressure is normal, except following severe birth asphyxia, or in mechanically ventilated preterm infants, who subsequently develop major germinal layer hemorrhage. The low level of cerebral blood flow (CBF) matches a low cerebral metabolism of glucose and a relatively small number of cortical synapses in the perinatal period. It has not been possible to define a threshold for GCBF below which electrical dysfunction or brain damage occurs (such as white matter and thalamic‐basal ganglia necrosis). Three explanations for the lack of clear relation between GCBF and electrical brain activity of the preterm infant must be examined more closely: 1) low levels of CBF are adequate; 2) GCBF does not adequately reflect critically low perfusion of the white matter, and 3) acute white matter ischemia does not result in electrical silence. Two clinical patterns of brain damage following asphyxia may be explained by changes in the blood flow distribution induced by asphyxia: brainstem sparing and parasagittal cerebral injury. Hours to days after severe asphyxia, a state of marked global hyperperfusion may prevail. It is associated with poor neurological outcome and may be an entry point for trials of interventions aiming sat blocking the translation of asphyctic injury to cellular death and tissue damage.
Cerebral Carbohydrate and Energy Metabolism in Perinatal Hypoxic‐Ischemic Brain Damage
Authors: Vannucci Robert C.
Published: January 2008

Cerebral hypoxia‐ischemia remains a major cause of acute perinatal brain injury. Research in experimental animals over the past decade has greatly expanded our knowledge of those oxidative events which occur during a hypoxic‐ischemic insult to the brain, as well as those metabolic alterations which evolve during the recovery period following resuscitation. The available evidence suggests that hypoxia alone does not lead to brain damage, but rather a combination of hypoxia‐ischemia or isolated cerebral ischemia is a necessary prerequisite for tissue injury to occur. Furthermore, hypoxia‐ischemia severe enough to produce irreversible tissue injury is always associated with major perturbations in the energy status of the perinatal brain which persists well into the recovery period. The lingering energy depletion sets in motion a cascade of biochemical alterations that are initiated during the course of the insult and proceed well into the recovery period to culminate in either neuronal necrosis or infarction. Unlike the adult, where glucose supplementation prior to or during hypoxia‐ischemia accentuates tissue injury, glucose treatment of perinatal animals subjected to a similar insult substantially reduces the extent of tissue injury. The mechanism for the age‐specific effect of glucose on hypoxic‐ischemic brain damage is discussed in relation to pathogenetic mechanisms responsible for the occurrence of permanent brain damage.
Excitatory Amino Acids Contribute to the Pathogenesis of Perinatal Hypoxic‐Ischemic Brain Injury
Authors: Barks John D.E. , Silverstein Faye S.
Published: January 2008

A large body of experimental evidence indicates that over‐activation of excitatory amino acid (EAA) receptors may mediate irreversible neuronal injury in a variety of pathologic settings including cerebral ischemia, and that the developing brain may be particularly susceptible to the adverse effects of EAA receptor overactivation. In this article, we review current information about EAA receptor pharmacology and EAA neurotoxicity in the immature brain, and summarize recent experimental data indicating that EAA contribute to the pathogenesis of perinatal hypoxic‐ischemic brain injury.
Heat Shock Proteins in Hypoxic‐Ischemic Brain Injury: A Perspective
Authors: Dwyer Barney E. , Nishimura Robert N.
Published: January 2008

There is much to suggest that the induction of heat shock protein synthesis is an important response to injury and stress in the brain. The role of heat shock proteins in neurological disease has been approached from two points‐of‐view. First, the induction and synthesis of specific proteins after brain cell injury provide a window through which insight on the regulation of gene expression in pathological tissue can be obtained. These studies have broad implications for understanding pathophysiological mechanisms of disease. Second, putative cell protective effects of heat shock proteins in brain tissue provide insight into biochemical mechanisms of selective neuronal vulnerability. These studies have extremely important clinical implications since cell sensitivity to injury can seemingly be modified. The role of heat shock proteins in hypoxic‐ischemic brain injury is discussed forthwith.
Drainage of Brain Extracellular Fluid into Blood and Deep Cervical Lymph and its Immunological Significance
Authors: Cserr Helen F. , Harling‐Berg Christine J. , Knopf Paul M.
Published: January 2008

Cerebral extracellular fluids drain from brain to blood across the arachnoid villi and to lymph along certain cranial nerves (primarily olfactory) and spinal nerve root ganglia. Quantification of the connection to lymph in rabbit, cat and sheep, using radiolabeled albumin as a marker of flow, indicates that a minimum of 14 to 47% of protein injected into different regions of brain or cerebrospinal fluid passes through lymph. The magnitude of the outflow to lymph is at variance with the general assumption that the absence of conventional lymphatics from the brain interrupts the afferent arm of the immune response to brain antigens. The immune response to antigens (albumin or myelin basic protein) introduced into the central nervous system (CNS) has been analysed using a rat model with normal brain barrier permeability. The micro‐injection of antigen into brain or cerebrospinal fluid elicits a humoral immune response, with antibody production in cervical lymph nodes and spleen, and also affects cell‐mediated immunity. Furthermore, antigen may be more immunogenic when administered into the CNS than into conventional extracerebral sites. Clearly, the afferent arm of the immune response to antigens, within the CNS, is intact. Modern studies suggest that the efferent arm is also intact with passage of activated lymphocytes into the brain. Results support a new view of CNS immunology which incorporates continuous and highly regulated communication between the brain and the immune system in both health and disease.
The X‐Linked Dystonia‐Parkinsonism Syndrome (XDP): Clinical and Molecular Genetic Analysis
Authors: Graeber Manuel B. , Müller Ulrich
Published: January 2008

Dystonia and parkinsonism are two major representatives of movement disorders. The X‐linked dystonia‐parkinsonism syndrome (XDP) serves as a model system for the study of both dystonia and parkinsonism since both symptom complexes occur together and are inherited as Mendelian traits with very high penetrance. XDP, which is endemic to the Philippine island of Panay, originated by a single mutation (“genetic founder effect”), thus assuring homogeneity of the disorder at the molecular level. The disease locus, DYT3, has been assigned to the proximal long arm (Xq12‐21.1) of the human X chromosome. A strategy is described to isolate this gene by positional cloning. The rationale of this strategy, the major methods involved and technical terms are explained.
New Insights Into the Clinical Features, Pathogenesis and Molecular Genetics of Huntington Disease
Authors: Kremer Berry , Weber Bernhard , Hayden Michael R.
Published: January 2008

Traditionally, a clinical diagnosis of Huntington disease (HD) presents no problems in patients with a positive family history, consistent with autosomal dominant inheritance, chorea or other extrapyramidal motor signs, and progressive mental decline (1). However, due to the slowly progressive nature of the disease and the slow evolution of signs and symptoms, it is often difficult to determine when at risk individuals are showing early signs. Moreover, the clinical recognition of both early and late‐onset cases, and of choreic patients in whom a family history is lacking, presents special diagnostic challenges.

In recent years, much progress has been made in the recognition of early clinical signs of the disease. Factors which have contributed to this understanding include the longitudinal study of large cohorts of at‐risk individuals, particularly in Venezuela, the data from predictive testing programs, and the application of positron emission tomography (PET)‐scanning to individuals without overt chorea. We are now able to identify persons at risk as being affected before they display overt and obvious involuntary movements.