An Immunohistochemical Study of the Distribution of the Measles Virus Receptors, CD46 and SLAM, In Normal Human Tissues and Subacute Sclerosing Panencephalitis

We have compared the expression of the known measles virus (MV) receptors, membrane cofactor protein (CD46) and the signaling lymphocyte-activation molecule (SLAM), using immunohistochemistry, in a range of normal peripheral tissues (known to be infected by MV) as well as in normal and subacute sclerosing panencephalitis (SSPE) brain. To increase our understanding of how these receptors could be utilized by wild-type or vaccine strains in vivo, the results have been considered with regard to the known route of infection and systemic spread of MV. Strong staining for CD46 was observed in endothelial cells lining blood vessels and in epithelial cells and tissue macrophages in a wide range of peripheral tissues, as well as in Langerhans' and squamous cells in the skin. In lymphoid tissues and blood, subsets of cells were positive for SLAM, in comparison to CD46, which stained all nucleated cell types. Strong CD46 staining was observed on cerebral endothelium throughout the brain and also on ependymal cells lining the ventricles and choroid plexus. Comparatively weaker CD46 staining was observed on subsets of neurons and oligodendrocytes. In SSPE brain sections, the areas distant from lesion sites and negative for MV by immunocytochemistry showed the same distribution for CD46 as in normal brain. However, cells in lesions, positive for MV, were negative for CD46. Normal brain showed no staining for SLAM, and in SSPE brain only subsets of leukocytes in inflammatory infiltrates were positive. None of the cell types most commonly infected by MV show detectable expression of SLAM, whereas CD46 is much more widely expressed and could fulfill a receptor function for some wild-type strains. In the case of wild-type stains, which are unable to use CD46, a further as yet unknown receptor(s) would be necessary to fully explain the pathology of MV infection.

Mesenchymal stem cells in immunoregulation

Mesenchymal stem cells (MSCs) reside within the bone marrow cavity and serve as a reservoir for the continuous renovation of various mesenchymal tissues. Recent efforts suggest that MSCs modulate the immune reactions in vitro and escape the immune surveillance in vivo. We provide herein a discussion of the issues including the current research progress on the in vitro interactions of MSCs with multiple subsets of immune cells (dendritic cells, T cells, B cells and natural killer cells), in vivo transplantation outcomes, the possible underlying mechanisms, future research directions as well as potential clinical implications.

Langerhans cells--revisiting the paradigm using genetically engineered mice.

Langerhans cells (LCs) are prominent dendritic cells (DCs) in epithelia, but their role in immunity and tolerance is poorly defined. 'Knockin' mice expressing enhanced green fluorescent protein (EGFP) under the control of the langerin (CD207) gene were recently developed in order to discriminate epidermal LCs from other DC subsets and at the same time to track their dynamics under steady-state or inflammatory conditions in vivo. Additional knockin mice expressing a diphtheria toxin receptor fused to EGFP were used to conditionally ablate LCs and assess their role in triggering hapten-specific T cell effectors through skin immunization. We review the insights that have been provided by these various knockin mice and discuss gaps in our knowledge of LCs that need to be filled.

Chondrogenic Differentiation Alters the Immunosuppressive Property of Bone Marrow-Derived Mesenchymal Stem Cells, and the Effect is Partially due to the Upregulated Expression of B7 Molecules

To investigate the immunosuppressive properties of mesenchymal stem cells (MSCs), in the present study we examined the immunogenicity of undifferentiated and tri-lineage (chondrocytes, osteoblasts and adipocytes) differentiated rat bone marrow-derived MSCs under xenogeneic conditions. After chondrogenic-differentiation, rat bone marrow-derived MSCs stimulated human peripheral blood monocyte-derived DCs (hDCs), leading to 8- and 4-fold higher lymphocyte proliferation and cytotoxicity than that of undifferentiated MSCs. The Chondrogenic-differentiated MSCs were chemotactic to hDCs in Dunn chamber chemotaxis system and were rosetted by hDCs inrosette assays. Flow cytometry analysis revealed that chondrogenic-differentiated MSCs had promoted hDCs maturation causing higher CD83 expression in hDCs, whereas undifferentiated MSCs, osteogenic-and adipogenic-differentiated MSCs showed inhibitory effect on hDCs maturation. The co-stimulatory molecules B7 were up-regulated only in the chondrogenic-differentiated MSCs. After blocking B7 molecules with specific monoclonal antibodies in the chondrogenic-differentiated MSCs, CD83 expression of co-cultured hDCs was greatly reduced. In conclusion, chondrogenic differentiation may increase the immunogenicity of MSCs, leading to stimulation of DCs. The up-regulated expression of B7 molecules on the chondrogenic differentiated MSCs may be partially responsible for this event.

The Galactic metallicity gradient

We have previously published intermediate to hi,oh resolution spectroscopic observations of approximately 80 early B-type main-sequence stars situated in 19 Galactic open clusters/associations with Galactocentric distances distributed over 6 less than or equal to R-g less than or equal to 18 kpc. This current study collates and re-analyses these equivalent- width datasets using LTE and non-LTE model atmosphere techniques, in order to determine the stellar atmospheric parameters and abundance estimates for C, N, O, Mg, Al and Si. The latter should be representative of the present-day Galactic interstellar medium. Our extensive observational dataset permits the identification of sub-samples of stars with similar atmospheric parameters and of homogeneous subsets of lines. As such, this investigation represents the most extensive and systematic study of its kind to date. We conclude that the distribution of light elements (CI O, Mg & Si) in the Galactic disk can be represented by a linear, radial gradient of -0.07 +/- 0.01 dex kpc(-1) Our results for nitrogen and oxygen viz. (-0.09 +/- 0.01 dex kpc(-1) and -0.067 +/- 0.008 dex kpc(-1)) are in excellent agreement with that found from the study of HII regions. We have also examined our datasets for evidence of an abrupt discontinuity in the metallicity of the Galactic disk near a Galactocentric distance of 10 kpc (see Twarog et al. 1997). However, there is no evidence to suggest that our data would be better fitted with a two-zone model. Moreover, we observe a N/O gradient of -0.04 +/- 0.02 dex kpc(-1) which is consistent with that found for other spiral galaxies (Vila- Costas gr Edmunds 1993).

The genetic basis of infertility in men.

Subfertility in men is a heterogeneous syndrome, its pathophysiology remaining unknown in the majority of affected men. A large number of genes and loci are associated with sterility in experimental animals, but the human homologues of most of these genes have not been characterized. A British study suggested that, in a large proportion of men with idiopathic infertility, the disorder is inherited as an autosomal recessive trait; this provocative hypothesis needs confirmation. Because normal germ cell development requires the temporally and spatially co-ordinated expression of a number of gene products at the hypothalamic, pituitary and testicular levels, it is safe to predict that a large number of autosomal, as well as X- and Y-linked, genes will probably be implicated in different subsets of male subfertility.

Prevalence of childhood abuse in mothers taking part in a study of parenting their own children.

This paper describes the incidence of maltreatment histories in a community sample of mothers of one-year old infants in Northern Ireland. The occurrence of five subsets of childhood maltreatment is examined: emotional abuse, emotional neglect, physical abuse, physical neglect and sexual abuse. Of the 201 women who completed the Childhood Trauma Questionnaire (CTQ), 70 mothers (35%) reported experiencing one or more types of maltreatment during childhood. Forty-eight mothers (24%) gave a history of being emotionally abused, 43 (21%) of emotional neglect, 27 (13%) of physical abuse, 20 (10%) of sexual abuse, and 19 (10%) of physical neglect. Physical abuse was the only type of maltreatment which showed an association with maternal socio-economic status, with higher incidence reported amongst Occupational Classes 4 and 5 (lower supervisory and technical occupations and semi-routine and routine groups). More than half of those with a history of abuse experienced more than one type of maltreatment (42 mothers or 60% of those reporting maltreatment). Differences in rates of incidence to more recent studies on younger adults are discussed, as well as implications for prevention and intervention.

Structure of spectra of linear operators in Banach spaces

Descriptive characterizations of the point, the continuous, and the residual spectra of operators in Banach spaces are put forward. In particular, necessary and sufficient conditions for three disjoint subsets of the complex plane to be the point spectrum, the continuous spectrum, and the residual spectrum of a linear continuous operator in a separable Banach space are obtained.

On stratifiable locally convex spaces

In the present paper we prove several results on the stratifiability of locally convex spaces. In particular, we show that a free locally convex sum of an arbitrary set of stratifiable LCS is a stratifiable LCS, and that all locally convex F'-spaces whose bounded subsets are metrizable are stratifiable. Moreover, we prove that a strict inductive limit of metrizable LCS is stratifiable and establish the stratifiability of many important general and specific spaces used in functional analysis. We also construct some examples that clarify the relationship between the stratifiability and other properties.

The pathophysiology of HOX genes and their role in cancer

The HOM-C clustered prototype homeobox genes of Drosophila, and their counterparts, the HOX genes in humans, are highly conserved at the genomic level. These master regulators of development continue to be expressed throughout adulthood in various tissues and organs. The physiological and patho-physiological functions of this network of genes are being avidly pursued within the scientific community, but defined roles for them remain elusive. The order of expression of HOX genes within a cluster is co-ordinated during development, so that the 3' genes are expressed more anteriorly and earlier than the 5' genes. Mutations in HOXA13 and HOXD13 are associated with disorders of limb formation such as hand-foot-genital syndrome (HFGS), synpolydactyly (SPD), and brachydactyly. Haematopoietic progenitors express HOX genes in a pattern characteristic of the lineage and stage of differentiation of the cells. In leukaemia, dysregulated HOX gene expression can occur due to chromosomal translocations involving upstream regulators such as the MLL gene, or the fusion of a HOX gene to another gene such as the nucleoporin, NUP98. Recent investigations of HOX gene expression in leukaemia are providing important insights into disease classification and prediction of clinical outcome. Whereas the oncogenic potential of certain HOX genes in leukaemia has already been defined, their role in other neoplasms is currently being studied. Progress has been hampered by the experimental approach used in many studies in which the expression of small subsets of HOX genes was analysed, and complicated by the functional redundancy implicit in the HOX gene system. Attempts to elucidate the function of HOX genes in malignant transformation will be enhanced by a better understanding of their upstream regulators and downstream target genes.

A Context-Dependent Algorithm for Merging Uncertain Information in Possibility Theory

The need to merge multiple sources of uncertaininformation is an important issue in many application areas,especially when there is potential for contradictions betweensources. Possibility theory offers a flexible framework to represent,and reason with, uncertain information, and there isa range of merging operators, such as the conjunctive anddisjunctive operators, for combining information. However, withthe proposals to date, the context of the information to be mergedis largely ignored during the process of selecting which mergingoperators to use. To address this shortcoming, in this paper,we propose an adaptive merging algorithm which selects largelypartially maximal consistent subsets (LPMCSs) of sources, thatcan be merged through relaxation of the conjunctive operator, byassessing the coherence of the information in each subset. In thisway, a fusion process can integrate both conjunctive and disjunctiveoperators in a more flexible manner and thereby be morecontext dependent. A comparison with related merging methodsshows how our algorithm can produce a more consensual result.

Joined Spectral Trees for Scalable SPIHT-Based Multispectral Image Compression

In this paper, the compression of multispectral images is addressed. Such 3-D data are characterized by a high correlation across the spectral components. The efficiency of the state-of-the-art wavelet-based coder 3-D SPIHT is considered. Although the 3-D SPIHT algorithm provides the obvious way to process a multispectral image as a volumetric block and, consequently, maintain the attractive properties exhibited in 2-D (excellent performance, low complexity, and embeddedness of the bit-stream), its 3-D trees structure is shown to be not adequately suited for 3-D wavelet transformed (DWT) multispectral images. The fact that each parent has eight children in the 3-D structure considerably increases the list of insignificant sets (LIS) and the list of insignificant pixels (LIP) since the partitioning of any set produces eight subsets which will be processed similarly during the sorting pass. Thus, a significant portion from the overall bit-budget is wastedly spent to sort insignificant information. Through an investigation based on results analysis, we demonstrate that a straightforward 2-D SPIHT technique, when suitably adjusted to maintain the rate scalability and carried out in the 3-D DWT domain, overcomes this weakness. In addition, a new SPIHT-based scalable multispectral image compression algorithm is used in the initial iterations to exploit the redundancies within each group of two consecutive spectral bands. Numerical experiments on a number of multispectral images have shown that the proposed scheme provides significant improvements over related works.

Simvastatin Decreases Lipopolysaccharide-induced Pulmonary Inflammation in Healthy Volunteers

RATIONALE:
Simvastatin inhibits inflammatory responses in vitro and in murine models of lung inflammation in vivo. As simvastatin modulates a number of the underlying processes described in acute lung injury (ALI), it may be a potential therapeutic option.
OBJECTIVES:
To investigate in vivo if simvastatin modulates mechanisms important in the development of ALI in a model of acute lung inflammation induced by inhalation of lipopolysaccharide (LPS) in healthy human volunteers.
METHODS:
Thirty healthy subjects were enrolled in a double-blind, placebo-controlled study. Subjects were randomized to receive 40 mg or 80 mg of simvastatin or placebo (n = 10/group) for 4 days before inhalation of 50 microg LPS. Measurements were performed in bronchoalveolar lavage fluid (BALF) obtained at 6 hours and plasma obtained at 24 hours after LPS challenge. Nuclear translocation of nuclear factor-kappaB (NF-kappaB) was measured in monocyte-derived macrophages.
MEASUREMENTS AND MAIN RESULTS:
Pretreatment with simvastatin reduced LPS-induced BALF neutrophilia, myeloperoxidase, tumor necrosis factor-alpha, matrix metalloproteinases 7, 8, and 9, and C-reactive protein (CRP) as well as plasma CRP (all P < 0.05 vs. placebo). There was no significant difference between simvastatin 40 mg and 80 mg. BALF from subjects post-LPS inhalation induced a threefold up-regulation in nuclear NF-kappaB in monocyte-derived macrophages (P < 0.001); pretreatment with simvastatin reduced this by 35% (P < 0.001).
CONCLUSIONS:
Simvastatin has antiinflammatory effects in the pulmonary and systemic compartment in humans exposed to inhaled LPS.

CD207+ CD103+ dermal dendritic cells cross-present keratinocyte-derived antigens irrespective of the presence of Langerhans cells.

Recent studies have challenged the view that Langerhans cells (LCs) constitute the exclusive antigen-presenting cells of the skin and suggest that the dermal dendritic cell (DDC) network is exceedingly complex. Using knockin mice to track and ablate DCs expressing langerin (CD207), we discovered that the dermis contains five distinct DC subsets and identified their migratory counterparts in draining lymph nodes. Based on this refined classification, we demonstrated that the quantitatively minor CD207+ CD103+ DDC subset is endowed with the unique capability of cross-presenting antigens expressed by keratinocytes irrespective of the presence of LCs. We further showed that Y-Ae, an antibody that is widely used to monitor the formation of complexes involving I-Ab molecules and a peptide derived from the I-E alpha chain, recognizes mature skin DCs that express I-Ab molecules in the absence of I-E alpha. Knowledge of this extra reactivity is important because it could be, and already has been, mistakenly interpreted to support the view that antigen transfer can occur between LCs and DDCs. Collectively, these data revisit the transfer of antigen that occurs between keratinocytes and the five distinguishable skin DC subsets and stress the high degree of functional specialization that exists among them.

A general framework for measuring inconsistency through minimal inconsistent sets

Hunter and Konieczny explored the relationships between measures of inconsistency for a belief base and the minimal inconsistent subsets of that belief base in several of their papers. In particular, an inconsistency value termed MIVC, defined from minimal inconsistent subsets, can be considered as a Shapley Inconsistency Value. Moreover, it can be axiomatized completely in terms of five simple axioms. MinInc, one of the five axioms, states that each minimal inconsistent set has the same amount of conflict. However, it conflicts with the intuition illustrated by the lottery paradox, which states that as the size of a minimal inconsistent belief base increases, the degree of inconsistency of that belief base becomes smaller. To address this, we present two kinds of revised inconsistency measures for a belief base from its minimal inconsistent subsets. Each of these measures considers the size of each minimal inconsistent subset as well as the number of minimal inconsistent subsets of a belief base. More specifically, we first present a vectorial measure to capture the inconsistency for a belief base, which is more discriminative than MIVC. Then we present a family of weighted inconsistency measures based on the vectorial inconsistency measure, which allow us to capture the inconsistency for a belief base in terms of a single numerical value as usual. We also show that each of the two kinds of revised inconsistency measures can be considered as a particular Shapley Inconsistency Value, and can be axiomatically characterized by the corresponding revised axioms presented in this paper.