Immunotherapy of head and neck cancer

Understanding the mechanisms responsible for photodamage to the skin is most important for dermatology. 3-D cultures have been used as tools to mimic the in vivo situation for several years. We irradiated such a system containing human dermal fibroblasts cultured in collagen gels, a well-known model considered to be a dermal equivalent, which reproduces the interaction between cells and the surrounding extracellular matrix. The effects of solar irradiation (315-800 nm) on the steady-state levels of the mRNAs of extracellular matrix components (type I and III collagens) and their degrading enzymes (interstitial collagenase, MMP-1 and stromelysin 1, MMP-3) were measured. Exposure to low levels of solar radiation (0-10 J cm-2 in the UVA, i.e. suberythemal UVA doses) caused a transient decrease in type I procollagen mRNA, an increase in MMP-mRNA, and no change in type III procollagen mRNA steady-state levels. These results describe the early changes in the connective tissue of the skin following exposure to low-level solar stimulation, and may help explain the long-term changes in photodamaged skin.     

Abciximab therapy and unplanned coronary stent deployment: favorable effects on stent use, clinical outcomes, and bleeding complications. EPILOG Trial Investigators

BACKGROUND: Recent studies indicate that eradication of Helicobacter pylori might prevent peptic ulcer formation in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). On the other hand, gastric adaptation after repeated exposures to aspirin (ASA) is well documented but the influence of H. pylori on this process remains to be elucidated. AIM: To compare gastric damage and adaptation following repeated exposures to ASA in a group of patients with H. pylori infection, before and after eradication of the bacterium, and in H. pylori-negative controls. METHODS: Eight healthy volunteers without H. pylori infection and eight patients with duodenal ulcer (DU) history and H. pylori infection before and after H. pylori eradication were given ASA 2 g/day for a period of 14 days. Mucosal damage was evaluated by endoscopy and histology of biopsy samples. Gastric microbleeding, DNA synthesis in the gastric mucosa and mucosal expression, as well as luminal content of transforming growth factor-alpha (TGFalpha) were determined on days 0, 3, 7 and 14 of the ASA course. RESULTS: In all patients aspirin-induced gastric damage reached a maximum on day 3. In H. pylori-positive patients, this damage was maintained at a similar level up to day 14, whereas in H. pylori-negative controls and H. pylori-eradicated patients this damage significantly lessened on day 14 and was accompanied by elevated DNA synthesis as well as increased mucosal expression and luminal release of TGFalpha.     

Molecular mapping with functional antibodies localizes critical sites on the human IL receptor common gamma (gamma c) chain

The IL receptor common gamma (gamma c) chain is required for the formation of high affinity cytokine receptor complexes for IL-2, IL-4, IL-7, IL-9, and IL-15, and for signals regulating cell survival, growth, and differentiation. Our current understanding of how gamma c chain associates with multiple ligands and receptor subunits is drawn largely from its structural homology to the human growth hormone (hGH) receptor and known structure of the hGH/hGH receptor complex. These receptors share distinct features in their extracellular portions and are believed to function by a mechanism of ligand-induced association of receptor subunits. Here, we report the first directed mutational analysis of the human gamma c chain by alanine scanning conducted across seven regions likely to contain residues required for intermolecular contact. Functionally distinct, neutralizing anti-gamma c mAbs were employed to define critical residues. One particular mAb, CP.B8, unique in its ability to inhibit IL-2-, IL-4-, IL-7-, and IL-15-induced proliferation and high affinity cytokine binding of normal T cells as an intact mAb and as a Fab fragment, localized critical residues to four noncontinuous stretches, namely residues in loops AB and EF of domain 1, in the interdomain segment, and in loop FG of domain 2. Notably, these residues form a contiguous patch on the gamma c chain surface in a three-dimensional structural model. These results provide functional evidence for the location of contact points on gamma c chain required for its association with multiple ligands.     

Toxoplasmosis in goats in the Netherlands: a pilot study

A pilot-study was carried out on ten Dutch goat farms to see whether there is a relationship between farm management factors and the occurrence of toxoplasmosis. Questionnaires were used to collect information about farm management factors and blood samples were taken to determine the prevalence of toxoplasmosis on these farms. The mean prevalence was 47% (range 5-90%). The presence of kittens on a farm was a risk factor for a higher prevalence of toxoplasmosis.     

Analogue f.d.m. telephony transmission in optical fibres: the limitations of intermodulation distortion

The linearity of optical sources is a critical factor in analogue applications of optical fibres. The letter describes such considerations related to f.d.m. telephony, addressing both the l.e.d. and laser diode. From the information presented, conclusions are drawn on the viability of these applications.