Histological observations on the evolution of nutritional encephalomalacia in chick cerebellum

Summary A study was made of the histological alterations which occur in the development of nutritional encephalomalacia in the chick cerebellum. 3 categories of chicks were discernible according to severity of symptoms.The earliest changes consisted of focal edema in the folial and medullary white matter. These became progressively more severe and resulted in widespread spongy degeneration. Edema of the Purkinje layer consistently appeared and led to a separation of this layer from the underlying granular layer. Apparent capillary proliferation was noted in all layers and distention of blood vessels finally resulted in hemorrhage and in necrosis of the folia.Clinical signs occasionally occurred without apparent morphological alterations. The edematous process, when noted, was considered to be intracellular, involving glial elements in the white matter and the Golgi epithelial cells (Bergmann astroglia) in the Purkinje layer. The condition results from altered permeability of the cerebellar blood-brain barrier which is selectively affected by the metabolic changes brought about by vitamin E deficiency.

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Zusammenfassung Die histologischen Veränderungen in der Entwicklung von nutritiver Encephalomalacie im Kleinhirn des Huhnes wurden untersucht. Nach der Schwere der klinischen Symptome wurden 3 Gruppen von Tieren unterschieden.Die frühesten Veränderungen bestanden in Ödemherden im Läppchenmark und Marklager, die progredient an Schwere zunehmen und ausgedehnte spongiöse Degeneration bewirken. Ödem der Purkinje-Zellschicht trat regelmäßig auf und führte zu ihrer Ablösung von der darunterliegenden Körnerschicht. Deutliche Capillarproliferation war in allen Schichten erkennbar. Die Gefäßerweiterung führte schließlich zu Blutungen und Nekrosen in den Läppchen.Klinische Symptome traten gelegentlich ohne manifeste morphologische Läsionen auf. Der ödematöse Prozeß wurde, wenn nachweisbar, als intracellulär aufgefaßt. Er betraf Gliaelemente des Markes und die Golgi Epithelzellen in der Purkinje-Zellschicht (Bergmann Astroglia). Diese Veränderung ist bedingt durch Permeabilitätsveränderungen der cerebellaren Bluthirnschranke, die selektiv betroffen erscheint, wenn der Stoffwechsel durch Vitamin E-Mangel gestört wird.

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This investigation was supported by United States Public Health Service Grants HD 00217 and FR 05388.     

Internal models underlying grasp can be additively combined

Our ability to additively combine two learned internal models was investigated by studying the forces people generate when lifting objects with a precision grip. Subjects were required to alternately lift two objects of identical physical appearance but differing weight. Grip force scaling prior to lift-off was used to estimate the output of the internal model associated with each object. Appropriate internal models were formed when alternately lifting two objects of different weight. The objects were then combined by stacking them one upon the other, and the combined object was lifted. Results show that subjects can additively combine internal models of object dynamics but the sum is biased by a default estimate of the objects weight.     

Improvement of surface bioactivity on titanium by water and hydrogen plasma immersion ion implantation

We have investigated the surface bioactivity of titanium after water and hydrogen plasma immersion ion implantation. Plasma immersion ion implantation (PIII) excels in the surface treatment of components possessing a complicated shape such as medical implants. In addition, water and hydrogen PIII has been extensively studied as a method to fabricate silicon-on-insulator (SOI) substrates in the semiconductor industry and so it is relatively straightforward to transfer the technology to the biomedical field. In our investigation, water and hydrogen were plasma-implanted into titanium sequentially. Our objective is that water PIII introduces near-surface damages that trap hydrogen implanted in the subsequent step to improve the surface bioactivity while the desirable bulk properties of the materials are not compromised. Ti-OH functional groups can be detected on the (H(2)O+H(2))-implanted titanium surface by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy. After incubation in simulated body fluids (SBF) for cytocompatibililty evaluation in vitro, bone-like hydroxyapatite was found to precipitate on the (H(2)O+H(2)) implanted samples while no apatite was found on titanium samples plasma implanted with water or hydrogen alone. Human osteoblast cells were cultured on the (H(2)O+H(2))-implanted titanium surface and they exhibited good adhesion and growth. Our results suggest a practical means to improve the surface bioactivity and cytocompatibility of medical implants made of titanium.     

Cellular pathology changes in rat skin following intradermal injection of nerve growth factor: neutrophil-dependent and -independent events

Nerve growth factor (NGF) regulates the survival and development of specific populations of neurones and is involved in wound healing. A further area of study relating to the role of neurotrophins in the mature animal has concerned the possibility that NGF may be a pivotal mediator of inflammation and pain. It has previously been shown that injection of intradermal NGF can result in a neutrophil-dependent hyperalgesia in the rat. The purpose of the present study was to examine the pathological consequence of NGF injected intradermally into mature rat skin and to examine further the role of neutrophils. Standard histopathology techniques (H & E) were employed to determine inflammatory cell counts. Circulating neutrophils were depleted using an anti-rat neutrophil antiserum and results were compared to treatment with vehicle controls. Saline-pretreated rats exhibited normal circulating neutrophil numbers and the dorsal skin showed a significant increase of neutrophil and macrophages at 3 and 5 h and lymphocytes at 5 h after NGF treatment. By comparison, skin sites from neutrophil-depleted rats did not demonstrate a significant increase in neutrophil and macrophage accumulation after NGF administration. All NGF-treated sites, independent of pretreatment, demonstrated abnormal muscle fibre morphology and proliferation of the muscle sarcolemmal nuclei after NGF injection, indicative of tissue injury. In addition, oedema and some fibroplasia were also noted. Furthermore, fibrin production was increased at 3 and 5 h after NGF administration. It is suggested that NGF has a damaging effect on rat muscle which is independent of accumulating neutrophil and other inflammatory cells. In conclusion, the findings indicate a link between NGF-induced neutrophil and macrophage accumulation, as the increase in dermal macrophages was not observed in neutrophil-depleted rats. The results also suggest that NGF can have a profound effect on rat muscle and that this effect may be related to muscle regeneration.     

Antigen-specific production of interleukin (IL)-13 and IL-5 cooperate to mediate IL-4Ralpha-independent airway hyperreactivity

The pathogenesis of human asthma and the development of key features of pulmonary allergy in mouse models has been critically linked to IL-13. Analyses of the receptor components employed by IL-13 have shown that delivery of this cytokine to the airways of naive IL-4Ralpha gene targeted (IL-4Ralpha(-/-)) mice fails to induce disease, suggesting that this membrane protein is critical for transducing IL-13-mediated responses. The current study demonstrates that, in contrast to naive mice, T helper 2 bias, airways hyperreactivity (AHR) and tissue eosinophilia develop in Ovalbumin-sensitized IL-4Ralpha(-/-) mice and that these responses can be inhibited by the IL-13 antagonist sIL-13Ralpha2Fc. Therefore, antigen stimulation induces an IL-13-regulated response that is independent of IL-4Ralpha. To determine the role of IL-5 and eosinophils in the development of disease in antigen-exposed IL-4Ralpha(-/-) mice, pulmonary allergy was examined in mice deficient in both factors. IL-4Ralpha/IL-5(-/-) mice were significantly defective in their ability to produce IL-13 and failed to develop AHR, suggesting that IL-5 indirectly regulates AHR in allergic IL-4Ralpha(-/-) mice by an IL-13-dependent mechanism. Collectively, these results demonstrate that IL-13-dependent processes regulating the development of AHR and T helper bias persist in the in the lungs of allergic IL-4Ralpha(-/-) mice.     

Functional expression of 4-1BB (CD137) in the inflammatory tissue in Crohn's disease

4-1BB ligand (L) expressed on antigen presenting cells (APC) interacts with 4-1BB, expressed on activated T cells and this interaction costimulates T cells to secrete cytokines and to proliferate. We investigated whether 4-1BB/4-1BBL interactions might be involved in the pathogenesis of Crohn's disease (CD). In immunohistochemistry, we found 4-1BB expression on lamina propria (LP) cells in inflamed and to a lesser extend in non-inflamed gut tissue from CD patients. mRNA levels for 4-1BB were also elevated in intestinal CD tissue. In contrast, only few 4-1BB-expressing cells were found in inflamed tissue from ulcerative colitis (UC) patients and almost no positive cells were found in control intestinal tissue. 4-1BB expression was better sustained on in vitro activated lamina propria T cells from CD patients compared to controls. Finally, agonistic anti-4-1BB antibody enhanced interferon-gamma (IFN-gamma) production and proliferation of lamina propria T cells from CD patients. Taken together, our data suggest that 4-1BB/4-1BBL interactions contribute to the persistence of gut inflammation in CD.     

Fatal case of endocarditis due to Weissella confusa

This is the first reported case of endocarditis due to the Lactobacillus-like vancomycin-resistant gram-positive bacillus Weissella confusa. Full identification and susceptibility testing of Lactobacillus-like organisms recovered in blood culture should be performed for patients with clinical presentations that suggest endocarditis.     

The impact of DNA damage, genetic mutation and cellular responses on cancer prevention, longevity and aging: observations in humans and mice

Over the past 5 years, data collected from the mouse suggest that pathways important for either preventing or resolving DNA damage are longevity assurance mechanisms whose critical overall function is somatic cell maintenance, a necessary part of cancer prevention. These pathways include those that reduce DNA damage levels caused by exogenous sources, replication errors and by-products of cellular respiration. Unresolved DNA damage leads to permanent mutations in the genetic code that may be oncogenic. Therefore, pathways that resolve DNA damage are important anti-cancer mechanisms. As an important line of defense, there are a variety of pathways that repair DNA damage. In addition, there are anti-cancer pathways that respond to DNA damage by either preventing cellular replication or inducing cell death. Genes in these pathways, termed longevity assurance genes (LAG), code for proteins that reduce cancer incidence and as a result assures a sufficiently long health span needed for reproduction. Data from mouse models, many that were originally designed to study cancer, are showing that a potential consequence of DNA damage and responses to DNA damage is aging; these models support the hypothesis that at least some aspects of normal aging are the consequence of anticancer mechanisms designed to deal with damaged DNA.     

Immune Adherence of Platelets to Sensitized Leukocytes: a Model of Hyperacute Rejection

Specifically hypersensitized recipients of canine renal allotransplants demonstrate an accumulation of host platelets in the transplanted kidney within minutes following implantation. Transplant function is ra,idly lost. The present work describes an in vitro model of this hyperacute rejection mechanism. Renal donor leukocytes sensitized with host serum are incubated with donor platelets. Within a few minutes the platelets adhere to the sensitized leukocytes to form rosettes. Serum complement is required for platelet rosette formation. Platelets act as indicators in this reaction and they may be obtained from any dog. Donor platelets were used to avoid the transfer of specific antibody to the test mixture. The in vitro model supports the view that hyperacute rejection in the dog is a specific example of the immune adherence reaction in which platelets bind to antigen-antibody-complement complexes.