Immunolocalization of MMP-19 in the human intervertebral disc: implications for disc aging and degeneration

Matrix metalloproteinases (MMPs) degrade components of the extracellular matrix of the disc, but the presence of MMP-19 has not been explored. In other tissues, MMP-19 is known to act in proteolysis of the insulin-like growth factor (IGF) binding protein-3, thereby exposing this protein to make it available to influence cell behavior. MMP-19 also has been shown to inhibit capillary-like formation and thus play a role in the avascular nature of the disc. Using immunohistochemistry, normal discs from six subjects aged newborn through 10 years and 20 disc specimens from control donors or surgical patients aged 15-76 (mean age 40.2 years) were examined for immunolocalization of MMP-19; six Thompson grade I discs, five Thompson grade II, eight Thompson grade III, five Thompson grade IV, and one Thompson grade V discs were analyzed. The results indicate that in discs from young subjects, MMP-19 was uniformly localized in the outer annulus. In discs from adult donors and surgical patients, outer and inner annulus cells only occasionally showed MMP-19 localization. The greatest expression of MMP-19 was observed in young discs, and little expression was seen in older or degenerating discs. Because MMP-19 has been shown to regulate IGF-mediated proliferation in other tissues, its decline in the aging/degenerating disc may contribute to the age-related decrease in disc cell numbers.     

The potential of seaweed as a source of drugs for use in cancer chemotherapy

This review discusses studies on marine macroalgae that have been investigated for their potential as sources of novel anti-cancer drugs. The review highlights the very large number of studies of crude, partially purified and purified seaweed extracts, collected from many locations, which have shown potential as sources of potent anti-cancer drugs when tested in vitro and/or in vivo. The activity of polysaccharides, polyphenols, proteinaceous molecules, carotenoids, alkaloids, terpenes and others is described here. In some reports, mechanistic studies have identified specific inhibitory activity on a number of key cellular processes including apoptosis pathways, telomerase and tumour angiogenesis. However, despite the potential shown by these studies, translation to clinically useful preparations is almost non-existent. It is hoped this review will serve as a source document and guide for those carrying out research into the potential use of macroalgae as a source of novel anti-cancer agents.     

Adaptive Immunity Alters Distinct Host Feeding Pathways during Nematode Induced Inflammation,a Novel Mechanism in Parasite Expulsion

Gastrointestinal infection is often associated with hypophagia and weight loss; however, the precise mechanisms governing these responses remain poorly defined. Furthermore, the possibility that alterations in feeding during infection may be beneficial to the host requires further study. We used the nematode Trichinella spiralis, which transiently inhabits the small intestine before migrating to skeletal muscle, as a biphasic model of infection to determine the cellular and molecular pathways controlling feeding during enteric and peripheral inflammation. Through the infection of genetically modified mice lacking cholecystokinin, Tumor necrosis factor α receptors and T and B-cells, we observed a biphasic hypophagic response to infection resulting from two separate immune-driven mechanisms. The enteroendocrine I-cell derived hormone cholecystokinin is an essential mediator of initial hypophagia and is induced by CD4+ T-cells during enteritis. In contrast, the second hypophagic response is extra-intestinal and due to the anorectic effects of TNFα during peripheral infection of the muscle. Moreover, via maintaining naive levels of the adipose secreted hormone leptin throughout infection we demonstrate a novel feedback loop in the immunoendocrine axis. Immune driven I-cell hyperplasia and resultant weight loss leads to a reduction in the inflammatory adipokine leptin, which in turn heightens protective immunity during infection. These results characterize specific immune mediated mechanisms which reduce feeding during intestinal or peripheral inflammation. Importantly, the molecular mediators of each phase are entirely separate. The data also introduce the first evidence that I-cell hyperplasia is an adaptively driven immune response that directly impinges on the outcome to infection.     

Expression of serglycin in human disc is increased in degenerated discs and up-regulated in vitro by exposure to IL-1ß or TNF-α

We investigated whether the multifunctional intercellular proteoglycan, serglycin, is expressed in human intervertebral disc cells and assessed its localization. We also investigated expression levels of serglycin in human annulus fibrosus (annulus) cells exposed to IL-1ß and TNF-α, which are two proinflammatory cytokines that are expressed during disc degeneration. Immunolocalization of serglycin was common in many cells of the human annulus, but less common in the nucleus pulposus (nucleus). Both intracellular and cell membrane localization were observed. Annulus cells from Thompson grades III, IV and V degenerated discs exhibited a 4.69 fold up-regulation in serglycin expression vs. cells from healthier grades I and II discs. In monolayer annulus cell culture, cells from more degenerated discs exhibited a 9.4 fold up-regulation of serglycin expression compared to cells from healthier discs. Exposure of cultured cells to IL-1ß or TNF-α caused significant up-regulation of serglycin expression. We found that serglycin expression increased with increasing disc degeneration both in vivo and in vitro, and also increased with exposure in vitro to IL-1ß and TNF-α.     

Taxon sampling effects on the quantification and comparison of community phylogenetic diversity

Ecologists are increasingly making use of molecular phylogenies, especially in the fields of community ecology and conservation. However, these phylogenies are often used without full appreciation of their underlying assumptions and uncertainties. A frequent practice in ecological studies is inferring a phylogeny with molecular data from taxa only within the community of interest. These “inferred community phylogenies” are inherently biased in their taxon sampling. Despite the importance of comprehensive sampling in constructing phylogenies, the implications of using inferred community phylogenies in ecological studies have not been examined. Here, we evaluate how taxon sampling affects the quantification and comparison of community phylogenetic diversity using both simulated and empirical data sets. We demonstrate that inferred community trees greatly underestimate phylogenetic diversity and that the probability of incorrectly ranking community diversity can reach up to 25%, depending on the dating methods employed. We argue that to reach reliable conclusions, ecological studies must improve their taxon sampling and generate the best phylogeny possible.     

X-ray diffraction study of the cornea

Low-angle X-ray diffraction patterns have been recorded from the cornea. A fibre diagram was obtained: the reflections from the axial period of collagen were on the equator while reflections from the collagen fibril lattice structure were on the meridian. Only the reflections from tha array of collagen fibrils have been studied. These reflections contain a primary first-order reflection and up to four subsidiary maxima. The first-order reflection from the array provides an estimate of the interfibril separation distance. Evidence is presented that the subsidiary maxima are consistent with the intensity transform of a uniform cylinder with a constant radius. Values for the fibril diameters and the interfibril distances are obtained for corneas from rabbit, cow and frog and from corneas of two marine fishes: toadfish and skate. Although the volume fraction of the collagen fibrils cannot be directly evaluated, an upper limit can be given. Thus, an upper limit of 0.28 was obtained for rabbit cornea.     

Direct Determination of the Lamellar Structure of Peripheral Nerve Myelin at Moderate Resolution (7 Å)

Low-angle X-ray diffraction patterns have been recorded from normal nerve and nerve swollen in glycerol solutions. The new X-ray data have a resolution of 7 Å. Direct methods of structure analysis which include deconvolution of the auto-correlation function and sampling theorem reconstructions have been used in the interpretation of the X-ray data. Phases have been assigned to the first 12 orders of diffraction from normal nerve. Fourier syntheses at a resolution of 7 Å are described and an absolute electron density scale is derived. A possible molecular interpretation of the electron density profile is given.     

Regional distribution of homocarnosine and other ninhydrin-positive substances in brains of malnourished monkeys

—Eight male monkeys (Macaca nemestrina) aged 6–9 months were divided into two groups and fed either an adequate protein diet (20% casein) or a protein deficient diet (2% casein). After 3- 5 months of receiving the low protein diet, the malnourished monkeys showed extensive fatty metamorphosis of the liver cells, distorted patterns of plasma and hepatic free amino acid pools, and other features consistent with the diagnosis of protein-calorie malnutrition. Examination of the cerebrum, cerebellum and brain stem in the malnourished animals revealed profound accumulation of 3-methylhistidine, histidine and homocarnosine in all three regions. For histidine, the cerebral, cerebellar and brain stem levels in the protein deficient animals increased by 145, 104 and 101 per cent over levels observed in corresponding regions of the brain in well-fed monkeys. Similarly, there were significant elevations in homocarnosine contents of the cerebrum (+ 99 per cent), cerebellum (+ 140 per cent) and brain stem (+ 146 per cent) in comparison to levels in control animals. In contrast, the levels of valine, serine and aspartic acid were markedly reduced in all three brain areas in the malnourished animals. Protein-calorie deficiency also produced reductions in the brain levels of taurine, glutamic acid, isoleucine, leucine and threonine which varied in magnitude in the three major regions of the brain examined. These biochemical alterations which may in part underlie some of the psychomotor changes often observed in protein-calorie malnutrition, were discussed not only in relation to the role of amino acids as precursors for the synthesis of neuroregulatory substances but also with due regard to the possibility that some of these ninhydrin-positive substances such as GABA, homocarnosine, glycine and the dicarboxylic amino acids may possess neuroexcitatory or inhibitory properties in various parts of the central nervous system.     

INTRODUCTION

.In view of the growing importance of fish for native consumption, the resources of the African lakes are sure to be exploited in the near future, but it is essential to have a sound understanding of the fish and other fauna and flora in each lake before exploitation is started. This paper places on record the available data for Lake Rudolf and Lake Baringo, on which no previous ecological work had been attempted.
Lake Rudolf is characterized by a high temperature and very alkaline water, and contains a variety of environments inhabited by different fish-associations. The fauna has pronounced nilotic affinities, except that there is only one member of the family Mormyridae. Several species, however, have come to differ from their nilotic ancestors, and the comparison of the fauna with that of other waters can be used as evidence for past changes in the drainage systems of East Africa.
The fish fauna of Lake Rudolf is roughly divisible into three main associations of species–one in the inshore waters, one in the open water, and one near the bottom. Prom data supplied by large numbers of stomach examinations, the food-chains for each of these habitats can be reconstructed.
Lake Baringo is less warm, the water has a relatively low alkalinity, and is uniformly shallow and muddy. The fish fauna consists of few species, and shows affinities with that of the East African rivers which flow to the Indian Ocean.
Owing to the shallowness of Lake Baringo, there is no differentiation into species-associations, and the food-chains are complicated by the presence of food from the bottom in all the species of fish.
The bulk of this paper contains analyses of field-observations on the size, feeding and breeding habits of each of the species found in the lakes,     

ANTIPYRETIC ACTION OF DEXAMETHASONE ON EGTAZIC ACIDINDUCED FEVER IN RABBITS

本文用脑室灌注和Ｆｕｒａ２测定细胞内游离钙技术观察了地塞米松（ｄｅｘａｍｅｔｈａｓｏｎｅ,ＤＥＸ）对家兔乙二醇双（２氨基乙醚）四乙酸性发热效应和下丘脑细胞内游离钙浓度（［Ｃａ２＋］ｉ）的影响,借此深入探讨地塞米松解热作用的中枢机制。结果发现：脑室灌注乙二醇双（２氨基乙醚）四乙酸（０６ｎｍｏｌ）引起家兔结肠温度明显升高,静脉注射地塞米松（５ｍｇ／ｋｇ）显著抑制家兔乙二醇双（２氨基乙醚）四乙酸性发热,地塞米松（６０～１２０μｍｏｌ／Ｌ）并不影响下丘脑细胞内［Ｃａ２＋］ｉ,而事先脑室灌注抑制基因转录的放线菌素Ｄ（３ｎｍｏｌ）则完全取消了地塞米松对乙二醇双（２氨基乙醚）四乙酸性发热的解热作用。这些结果提示：地塞米松显著抑制家兔乙二醇双（２氨基乙醚）四乙酸性发热,其机制与地塞米松激活脑内某些基因的表达有关,而与下丘脑神经细胞跨膜钙离子流无关。