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.     

Nutritional intervention and growth in children with chronic renal failure

During fifties there were at most few tens of persons in this country who believed in the future of computers and cybernetics. One group of such enthusiasts, headed by Antonín Svoboda, was working at a construction of the first Czech computer SAPO. The other group tried to analyse, anticipate, and prepare in advance various applications for the new systemic conceptions and for the information processing machines. Members of both groups met for discussions which opened prospects to the future and influenced many of other activities for a long time. At the early sixties, the Czechoslovak Cybernetic Society was established at the Czechoslovak Academy of Sciences and in 1962 the Main Problem Committee for the Medical Cybernetics was founded at the Department of Health. It coordinated majority of the research programmes in the medical cybernetics and informatics. In 1967-1969 the Committee prepared an extensive project of a medical information system (ZIS), but its accomplishment was finally blocked by the then authorities. However, interests for that topics kept growing and the new working places equipped with available computer technology were formed at the health and clinical centres. The first tentative lectures in medical cybernetics and biocybernetics at our faculty were introduced into the students curricula in the late sixties. Thematically, medical cybernetics subsequently differentiated into the medical informatics, simulations of biological and medical systems, and the biosignal analysis. The growing interest enabled to hold conferences since the middle of seventies, some of which were held periodically, sometimes with international participation. It is not possible in brevity to include the whole spectrum to those goal-directed activities nor to appraise adequately their future significance.     

Dependence of antibody somatic diversification on gut-associated lymphoid tissue in rabbits

By approximately 4 to 8 wk of age, the IgH VDJ genes of essentially all rabbit B lymphocytes have undergone somatic diversification. Some of this diversification occurs in the appendix, which is a gut-associated lymphoid tissue (GALT). To determine whether GALT is essential for somatic diversification, we surgically removed the appendix, sacculus rotundus, and Peyer's patches from neonatal rabbits (designated GALT-less) and examined the extent to which VDJ genes were somatically diversified. We found that the IgM VDJ genes of peripheral B cells from 2- to 5-mo-old GALT-less rabbits had undergone considerably less somatic diversification than those of control rabbits. Further, the percentage of peripheral B cells in the GALT-less rabbits was generally less than that of controls. Our data suggest that, in rabbits, the primary Ab repertoire develops in GALT, and B cell expansion also occurs there. Hence, GALT may function as a mammalian bursal homologue.