The role of relative osteoneural growth in the gross morphogenesis of the skeleton: A hypothesis

Summary A unifying concept of gross skeletal (neurocranial, neurospinal and appendicular) morphogenesis is proposed. It is based on a close developmental relationship of bone and the nervous tissue, most evident in the neurocranium. The neurospinal developmental interrelationship is modified by the neurovertebral growth differential, which appears to influence the development of spinal curvatures and the gross morphological features of the individual vertebrae. Disproportion in osteoneural growth, as a general biological phenomenon, would be expected to affect the development of the appendicular skeleton. The gross shape of the long bones (physiological curvature and epimetaphyseal widening/modelling) appear to result from a buildup of rapidly forming skeletogenic material adjacent to slower growing nervous trunks, as is the case with the enchondrally developing vertebral body.Pathological accentuation of vertebro-osteoneural growth disproportion, brought about mainly by inhibition of the vulnerable neural growth, will result in abnormal gross features of the skeleton, i.e., pathological curvatures, terminal or general thickening and shortening of bones, or dislocation of joints. Experimental and clinical deformities, such as idiopathic scoliosis, achondroplastic conditions, congenital dislocation of the hip joint, and some other bone dysplasias confined in their onset and progression to the growth period of life, seem to be related to the suggested mechanism. For the above-mentioned skeletal disorders the term osteoneural growth pathology is proposed.

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Le rôle de la croissance relative ostéo-neurale dans la morphogénèse du squelette. Une hypothèse

Résumé On propose une conception unitaire de la morphogénèse normale et pathologique du squelette axial et appendiculaire, à partir des relations les plus étroites existant entre la croissance des systèmes osseux et nerveux; la région neurocraniale en est la manifestation la plus expressive. La disproportion de croissance neuro-vertébrale en longueur exerce une influence décisive sur l'installation des courbures vértébrales physiologiques et sur les caractères morphologiques de chacune des vertèbres, aussi bien dans les dimensions des corps vértébraux que la forme du trou vertébral et des trous de conjugaison. Evoquant un phénomène biologique général, la disproportion de croissance ostéo-neurale agit de même sur le développement du squelette des membres. La forme, c'est-à-dire leurs courbures physiologiques et le modelage de la région épi-métaphysaire peuvent aussi être rattachés à un phénomène d'amassement de tissus osseux proliférant plus rapidement le long des troncs nerveux périphériques.L'accentuation pathologique de la disproportion de croissance ostéo-neurale, du fait principalement de l'inhibition de la croissance des structures nerveuses peut aboutir à des modifications des parties correspondantes du squelette avec effets de raccourcissement, de courbures pathologiques, d'élargissement partiel ou total et éventuellement, de dislocation articulaire. La conception proposée s'appuie sur des observations expérimentales de croissance ostéo-neurale chez des embryons d'oiseaux et d'amphibiens. On peut expliquer certaines déformations du squelette expérimentales ou cliniques comme la scoliose idiopathique, l'achondroplasie et la dysplasie congénitale de hanche par un même mécanisme d'adaptation des os en croissance à des troubles du développement des structures nerveuses avoisinantes. Une dénomination commune est proposée pour ces troubles de la croissance: pathologie de la croissance relative ostéo-neurale.

     

Bromsulfalein-Kinetik mit albumingebundenem BSP

Zusammenfassung Die Beeinflussung der BSP-Kinetik durch Zusätze von Albumin zur Injektionslösung wurde geprüft. Bei einer Dosierung von 5 mg BSP pro kg Körpergewicht bleibt die Eliminationshalbwertzeit bis zu einem BSP-Albuminverhältnis von 1:10 (w/w) unverändert, nach größeren Albumingaben ist sie signifikant verlängert.F.H. Dost zum 65. Geburtstag zugeeignet     

Effect of synthetic lipopeptides formulated in liposomes on the maturation of human dendritic cells

Diacylated (e.g. MALP-2) and triacylated (Pam(3)Cys derivatives) lipopeptides, deriving from the N-terminal moiety of respectively mycoplasmal and E. coli lipoproteins, are powerful adjuvants recognized by Toll-like receptors (TLR) which have been used successfully to trigger cell activation and immune responses. To design liposome-based vaccination constructs in which Th and CTL epitopes are conjugated to synthetic lipopeptide analogues anchored into the bilayers of the vesicles, the peptide moieties of the lipopeptides were functionalized with thiol-reactive groups, such as maleimide (Mal) or bromoacetyl, incorporated into liposomes and reacted with thiol carrying peptide epitopes. Because dendritic cells (DCs) play a key role as antigen-presenting cells in immune responses, in the present study we have evaluated the impact of the functionalization of lipopeptide analogues Pam(2)CAG, Pam(3)CAG and Ol(3)GAG on the phenotypic maturation of human monocyte-derived DCs. The intrinsic cellular activities of the lipopeptide analogues incorporated into liposomes were monitored, in vitro, by measuring the up-regulation of the cell-surface markers CD80, CD83, CD86 and HLA-DR. We found that in some cases their functionalization with thiol-reactive groups led to a loss of activity. The stimulatory potency can be ranked in the following order: Pam(3)CAG>/=Pam(2)CAG-Mal-Th approximately Pam(2)CAG-Mal>Pam(3)CAG-Mal-Th (where Th is a HS-peptide) and no appreciable activity was detected for Pam(3)CAG-Mal, Ol(3)CAG-Mal and Ol(3)CAG-Mal-Th. Our findings indicate that subtle modifications in the peptide moiety of lipopeptides have a great impact on the immunomodulatory properties of these molecules. For the engineering of liposome/lipopeptide-based vaccines, the maleimide derivative of Pam(2)CAG appears to be the best candidate.     

Immunoelectron microscopic investigation of surface coat of Wilms tumor cells. Dense lamina is composed of highly sialylated neural cell adhesion molecule

In previous studies we demonstrated the presence of polysialic acid in Wilms tumor by immunohistochemistry and immunoblotting. We now show by immunoelectron microscopy that the cell surface coat of Wilms tumor cells consists of a layer of amorphous material containing polysialic acid but not detectable amounts of laminin, laminin-nidogen complex, or low density proteoglycan. Therefore, Wilms tumor cells are covered by a highly developed and chemically specialized cell surface coat that does not represent a basement membrane, although it bears some structural similarities. Polysialic acid is present on neural cell adhesion molecule that exists in Wilms tumor as two isoforms of approximately 120 and 140 kDa. The cell surface coat exhibits variation in its thickness along the plasma membrane of a single tumor cell, and the variation is inversely related to the extent of cell-cell contact. It is therefore proposed that polysialic acid may modulate the behavior and invasive potential of Wilms tumor cells.     

Interpretation of skeletal muscle four-electrode impedance measurements using spatial and temporal frequency-dependent conductivities

Spatial and temporal frequency-dependent conductivities are used to interpret four-electrode conductivity measurements on skeletal muscle. The model qualitatively explains the observed dependence of the experimental data on the temporal frequency of the injected current, the angle between the electrode array and the fibre direction and the distance between the electrodes.     

The effect of tyrphostin AG-556 on intimal thickening in a mouse model of arterial injury

BACKGROUND: Inflammation has been shown to play an important role in promoting the response to arterial injury and proinflammatory cytokines, such as tumor necrosis factor (TNF) alpha, are candidate mediators. AG-556 is a tyrosine kinase inhibitor proven to be effective in a model of multiple sclerosis-like syndrome in mice due to its immunomodulating effect. In the current study, we investigated the effect of the tyrphostin AG-556 on neointimal thickening and cytokine profile in a model of arterial injury in the mouse. METHODS: Injury was induced by external cuff placement on the left femoral artery of wild-type C57BL/6 mice. AG-556 dissolved in DMSO was injected intraperitoneally daily to the injured mice in a dosage of 2 mg/mouse. Control mice received DMSO injections. Histological analysis was carried out to assess neointimal formation. Splenocytes were cultured in the absence and presence of a mitogen for evaluation of thymidine incorporation and cytokine production. RESULTS: AG-556 treatment significantly attenuated intimal thickening (43,000+/-17,000 microm2; n=11) when compared to DMSO administration (286,000+/-127,000 microm2; n=10; P<0.05). Basal interferon-gamma production by splenocytes from AG-556-treated mice was increased by approximately 20-fold in comparison with levels in DMSO-treated animals, whereas Con-A induced secretion of the cytokine was similar between both groups. Levels of TNF-alpha, IL-4 and IL-10 in the culture supernatant from treated and non-treated animals did not differ significantly. CONCLUSION: The tyrosine kinase inhibitor AG-556 may have a role in the reduction of intimal thickening. The effect could be mediated via an immune modulating effect involving a significant increase in the smooth muscle cell inhibitory cytokine IFN-gamma.     

Protection of early phase hepatic ischemia-reperfusion injury by cholinergic agonists

Background  

Cytokine production is critical in ischemia/reperfusion (IR) injury. Acetylcholine binds to macrophages and inhibits cytokine synthesis, through the cholinergic anti-inflammatory pathway. This study examined the role of the cholinergic pathway in cytokine production and hepatic IR- injury.     

No evidence for transmission disequilibrium between a new marker at the myelin basic protein locus and multiple sclerosis in French patients

The myelin basic protein (MBP) gene is a candidate locus for susceptibility to multiple sclerosis. Several groups have tested a complex (TGGA)n repeat in the 5' region of this gene for association/linkage with multiple sclerosis, with divergent results. This region of tandem repetitive sequence has been subjected to complex rearrangements, and there is a possibility that alleles of the same size have different internal structures, which reduces the interest of this marker for linkage disequilibrium studies and may at least partly explain the conflicting results obtained so far. To overcome this problem, we isolated a new polymorphic (CA)n repeat within the Golli-MBP locus. The limited number of alleles identified makes this other marker suitable for transmission disequilibrium studies. We tested this marker for linkage with multiple sclerosis, using the transmission-disequilibrium test (TDT) on a sample of 196 nuclear families in which the genotypes of both parents could be unambiguously defined. We found no evidence of transmission disequilibrium between multiple sclerosis and any of the three alleles of this marker, even when the patients were subdivided according to their HLA-DRB1*1501 status. The present data thus provide no evidence for a contribution of the MBP gene to multiple sclerosis susceptibility in French patients.     

The possible role of protein degradation in altered membrane structure and function

Possible changes in membrane lipid assemetry may result in altered function with aging. Membrane proteolysis is an additional factor which must be considered, both with respect to modulation of membrane function and also as a methodological problem in analyses of membrane dynamics.