Reciprocal T-B determinant spreading develops spontaneously in murine lupus: implications for pathogenesis

Summary: Recent work from several laboratories has shown that, in contrast to the widely held notion that one autoimmune disease is caused by one or a few related autoantigenic determinants, autoimmunity is fundamentally a continuously evolving process. The autoimmune responses shift, drift and diversify with time not only to other determinants in the original antigen but also to other antigens. We have described a form of determinant spreading - reciprocal T-B determinant spreading–where the induction of first T cells by peptides from an autoantibody molecule could lead to help provided to a variety of B cells displaying a cross-reactive version of the original determinant. The response spreads in this way by reciprocal T-B stimulation until large cohorts of T and B cells have expanded. Such spontaneous expansion must be important in clinical disease, since tolerance induction to a limited set of T-cell determinant peptides derived from an anti-DNA antibody VH region delayed the appearance of IgG anti-dsDNA antibodies and onset of lupus nephritis in the NZB/NZW Fl mouse model of systemic lupus erythematosus. Understanding the diversification patterns in autoimmune responses has enormous implications in developing peptide-targeted therapies.     

The mutual clonal origin of the lymphoplasmocytic and lymphoma cell in alpha-heavy chain disease.

Biosynthetic studies in alpha-heavy chain disease were performed on the gut tumour which was composed mainly of lymphoplasmocytic cells and on the mesenteric lymph node tumour composed mainly of immunoblasts. The gut tumour cells synthesised alpha-heavy chains and secreted them during 2-5 hr culture, whereas the lymph node tumour cells synthesized alpha-heavy chains which were shed into the culture medium only after 20 hr. These chains were shown to be present on the surface of the immunoblastic tumour cells by enzymatic radioiodination. Both the surface and the secreted alpha-heavy chain of the lymph node and gut tumour were found to be smaller than the alpha-heavy chain of myeloma proteins. These results suggest that the lymphoblasmocytic and the immunoblastic tumour cells originate from the same defective clone.     

Resting whole blood viscosity of elite rowers is related to performance

This study investigated the relationships between resting whole blood viscosity (WBV), haemoglobin concentration (HGB), haematocrit (HCT), and performance in 25 highly-trained national squad rowers (11 women and 14 men). The WBV and HGB were measured at rest prior to a 2500 m simulated race on a Concept rowing ergometer when performance (P) was measured by average velocity. A group of 12 rowers were measured on just one occasion, another 11 were measured twice with an intervening 5 weeks of continued training and 2 were measured three times, the third test after another 4 weeks. Regression analyses making simultaneous use of both intra- and interindividual data indicated a significant inverse relationship between P and WBV (at both high and low shear rates), a relationship which was strengthened after statistically controlling for the effects of HGB, this effect being slightly more significant than HCT. A significant positive regression also emerged between P and HGB, but only after statistically controlling for the influence of WBV at high shear rate. Overall, stronger relationships were demonstrated in the male rowers compared with the female. These data, in the light of previous evidence that fitter people tend to have lower WBV, would indicate that blood rheology unrelated to HGB (or HCT) is related to performance in relatively homogeneous and already highly-trained athletes.     

Relations between the brain and the endocrine system from its chronobiological aspects. II. The hypophysis, adrenal gland, thyroid islet organ, gonads and kidney

The presence of biorhythms in the endocrine organs (pituitary gland, adrenal gland, thyroid gland, islet organ, gonades , and kidney) are reviewed. Biorhythms ( circadian and circannual rhythms) have an influence on the action of this organs. The acrophases of the hormones in the serum have different peaks and their time-correlation is different. The importance of this data for experiments and for the clinical practice is discussed.     

Histamine content and histamine secretion of the colonic mucosa in patients with collagenous colitis

OBJECTIVE AND DESIGN: There is increasing evidence for the involvement of reactive nitrogen species like peroxynitrite (ONOO-) in airway pathology, for example during allergic airway inflammation. Therefore, the effect of peroxynitrite exposure on airway responsiveness and inflammation was studied. MATERIALS: Male BALB/c mice were treated intra-tracheally with authentic peroxynitrite and the peroxynitrite donor 3-morpholinosydnonimine (SIN-1). Control animals received decomposed solutions of peroxynitrite and SIN- 1. METHODS: Airway inflammation was monitored by bronchoalveolar lavage, three and seven days after administration. Airway responsiveness to methacholine and acetylcholine was measured on day 1, 2, 3 and 7 post administration using whole body plethysmography. RESULTS: Intra-tracheal administration of peroxynitrite 200 microM in 50 microl phosphate buffered saline (PBS) induced a significant increase in macrophages (>35%, p < 0.05) in the airway lumen three days after administration. In contrast, neither intra-tracheal administration of authentic peroxynitrite (up to 5 mM) nor the peroxynitrite donor SIN-1 (1 mM, both intra-tracheal and nebulized) changed airway responsiveness to methacholine. Moreover, peroxynitrite (5 mM) did not alter responsiveness to acetylcholine. CONCLUSION: Administration of peroxynitrite directly into the airways of BALB/c mice, induces airway inflammation, but not airway hyperresponsiveness. It is suggested that antioxidants in the epithelial lining fluid and/or the epithelium itself form an efficient barrier, which prevents peroxynitrite from reaching putative targets in the airway interstitium.     

Computers in clinical assessment: historical developments, present status, and future challenges

Computerized testing methods have long been regarded as a potentially powerful asset for providing psychological assessment services. Ever since computers were first introduced and adapted to the field of assessment psychology in the 1950s, they have been a valuable aid for scoring, data processing, and even interpretation of test results. The history and status of computer-based personality and neuropsychological tests are discussed in this article. Several pertinent issues involved in providing test interpretation by computer are highlighted. Advances in computer-based test use, such as computerized adaptive testing, are described and problems noted. Today, there is great interest in expanding the availability of psychological assessment applications on the Internet. Although these applications show great promise, there are a number of problems associated with providing psychological tests on the Internet that need to be addressed by psychologists before the Internet can become a major medium for psychological service delivery.     

Changes in performance,maximal oxygen uptake and maximal accumulated oxygen deficit after 5, 10 and 15 days of live high:train low altitude exposure

Nineteen well-trained cyclists (14 males and 5 females, mean initial V˙O_2max 62.3 ml kg^–1 min^–1) completed a multistage cycle ergometer test to determine maximal mean power output in 4 min (MMPO_4min), maximal oxygen uptake (V˙O_2max) and maximal accumulated oxygen deficit (MAOD). The athletes were divided into three groups, each of which completed 5, 10 or 15 days of both a control condition (C) and live high:train low altitude exposure (LHTL). The C groups lived and trained at the ambient altitude of 610 m. The LHTL groups spent 8–10 h night^–1 in normobaric hypoxia at a simulated altitude of 2,650 m, and trained at the ambient altitude of 610 m. The changes to MMPO_4min, V˙O_2max and MAOD in response to LHTL altitude exposure were not significantly different for the 5-, 10- and 15-day treatment periods. For the pooled data from all three treatment periods, there were significant increases in MMPO_4min [mean (SD) 5.15 (0.83) W kg^–1 vs 5.34 (0.78) W kg^–1] and MAOD [50.1 (14.2) ml kg^–1 vs 54.9 (13.1) ml kg^–1] in the LHTL athletes between pre- and post-altitude exposure. There were no significant changes in MMPO_4min [5.09 (0.76) W kg^–1 vs 5.16 (0.86) W kg^–1] or MAOD [50.5 (14.1) ml kg^–1 vs 49.1 (13.0) ml kg^–1] in the C athletes over the corresponding period. There were significant increases in V˙O_2max in the athletes during both the LHTL [63.2 (9.0) ml kg^–1 min^–1 vs 64.1 (9.0) ml kg^–1 min^–1] and C [62.0 (8.6) ml kg^–1 min^–1 vs 63.4 (9.2) ml kg^–1 min^–1] conditions. In these athletes, there was no difference in the impact of 5, 10 or 15 days of LHTL on the increases observed in MMPO_4min, V˙O_2max or MAOD; and LHTL increased MMPO_4min and MAOD more than training at low altitude alone. Electronic Publication