Adenoid cystic carcinoma of the lacrimal gland in a six-year-old girl

A 6-year-old white female was found to have an adenoid cystic carcinoma originating in a lacrimal gland. Eighteen months following diagnosis, the tumor recurred. Conservative surgery has been the sole mode of therapy. To date, after four operations and quadrimenstral imaging surveillance, there is no sign of disease progression. Our purpose is to record the unusual occurrence of an adenoid cystic carcinoma of the lacrimal gland in a child. An interim report, 32 months after diagnosis, is presented.     

The use of angiostatic steroids to inhibit cartilage destruction in an in vivo model of granuloma-mediated cartilage degradation

Angiogenesis is an important component of the development of chronic inflammatory diseases such as rheumatoid arthritis. It is known that clinically used anti-rheumatic drugs exert, in part, effects on the angiogenic response. Little work, however, has investigated the potential of experimental angiostatic therapies in chronic inflammatory disease models. The effect of one such angiostatic treatment, cortisone combined with heparin, was tested in an in vivo model of granuloma-mediated cartilage degradation. Angiostatic treatment significantly retarded the growth of granulomatous tissue, mononuclear cell influx into the granuloma, and the degradation of juxtaposed cartilage. This correlated with a decrease in the vascularity of the granulomatous tissue. Modulation of this component of pathogenesis of "angiogenesis-dependent disease" may be useful as a new therapeutic approach.     

Grafting of enzymes on collagen films using Woodward''s reagent "K" and a water-soluble carbodiimide derivative

Two new methods of activation were developed to graft enzymes on collegen films. They involved chemical modifications of surface groups of collagen either by Woodward's reagent "K" or by EDC, a water-soluble derivative of carbodiimide. EDC was a better coupling agent and a detailed study was conducted with this agent. It could be used either in a global method of activation and coupling, or in a two-step procedure of activation of collagen, followed by spontaneous coupling of enzyme. All enzymes tested were successfully bound: malate dehydrogenase, lactate dehydrogenase, aspartate aminotransferase, urease, creatine kinase, hexokinase. The influence on the yield of grafted enzyme, of pretreatment of films, time and temperature of EDC activation, concentration of EDC and enzyme, protecting agents was studied. Stability of enzyme activity on storage was greatly increased after grafting. A co-grafted dual system creatine kinase/heoxkinase, was achieved which exhibited a good efficiency. A striking renaturing process at 0-4degreesC after thermal denaturation, was observed with hexokinase.     

Nanobody Paratope Ensembles in Solution Characterized by MD Simulations and NMR

Variable domains of camelid antibodies (so-called nanobodies or V_HH) are the smallest antibody fragments that retain complete functionality and therapeutic potential. Understanding of the nanobody-binding interface has become a pre-requisite for rational antibody design and engineering. The nanobody-binding interface consists of up to three hypervariable loops, known as the CDR loops. Here, we structurally and dynamically characterize the conformational diversity of an anti-GFP-binding nanobody by using molecular dynamics simulations in combination with experimentally derived data from nuclear magnetic resonance (NMR) spectroscopy. The NMR data contain both structural and dynamic information resolved at various timescales, which allows an assessment of the quality of protein MD simulations. Thus, in this study, we compared the ensembles for the anti-GFP-binding nanobody obtained from MD simulations with results from NMR. We find excellent agreement of the NOE-derived distance maps obtained from NMR and MD simulations and observe similar conformational spaces for the simulations with and without NOE time-averaged restraints. We also compare the measured and calculated order parameters and find generally good agreement for the motions observed in the ps–ns timescale, in particular for the CDR3 loop. Understanding of the CDR3 loop dynamics is especially critical for nanobodies, as this loop is typically critical for antigen recognition.     

An Overview of the Latest Metabolomics Studies on Atopic Eczema with New Directions for Study

Atopic eczema (AE) is an inflammatory skin disorder affecting approximately 20% of children worldwide and early onset can lead to asthma and allergies. Currently, the mechanisms of the disease are not fully understood. Metabolomics, the analysis of small molecules in the skin produced by the host and microbes, opens a window to observe the mechanisms of the disease which then may lead to new drug targets for AE treatment. Here, we review the latest advances in AE metabolomics, highlighting both the lipid and non-lipid molecules, along with reviewing the metabolites currently known to reside in the skin.