IMMUNOGLOBULIN ISOANTIGENS (ALLOTYPES) IN THE MOUSE : I. GENETICS AND CROSS-REACTIONS OF THE 7S γ2A-ISOANTIGENS CONTROLLED BY ALLELES AT THE IG-1 LOCUS

Eight antigens of 7S γ₂-immunoglobulins controlled by alleles at a single locus Ig-1, have been identified in mice. This locus has previously been shown to determine antigenic specificities on the F fragments of 7S γ_2a-globulins. The reactions of these antigens with various isoantisera have shown that the antigens all cross react with one another. New methods for the analysis of antigenic specificities of soluble proteins are presented in detail. A sensitive method for detecting in the order of 0.01 µg of these isoantigens has been developed, based on the quantitative inhibition of precipitation of I¹²⁵-labeled antigen. Cross-reactions of the antigens were analysed in inhibition assays and the data is compatible with the existence of a minimum of eight antigenic specificities. Each of the antigens is composed of different combinations of these specificities, with only one antigen having a specificity not present in any other. Sixty-eight mouse strains have been tested with specific isoantisera, and on the basis of the results, have been placed into the eight allele groups. Evidence for close genetic linkage of the Ig-1 locus and 11 chromosome markers has been sought and not found.     

ACTIVE SUPPRESSION OF IMMUNOGLOBULIN ALLOTYPE SYNTHESIS : I. CHRONIC SUPPRESSION AFTER PERINATAL EXPOSURE TO MATERNAL ANTIBODY TO PATERNAL ALLOTYPE IN (SJL x BALB/c)F1 MICE

Long-term (chronic) allotype suppression, previously reported only in rabbits, is shown here to occur in at least one strain combination of mice as well. Close to 50% of the offspring of SJL (Ig^b) males mated to BALB/c (Ig^a) females immunized against the paternal allotype were found to be suppressed for Ig-1b (γG_2a) at 6 months of age. These mice are called "chronically" suppressed. The percentage of offspring in this strain combination suppressed for the paternal allotype at 8 wk of age is the same as that seen in an earlier strain combination tested, [(C57 x BALB/c)F₁], in which all mice recover from suppression by 10–12 wk. After 8 wk, two distinct patterns of long-term (chronic) suppression emerge in (SJL x BALB/c)F₁ mice: a small number of these mice never produce detectable amounts of Ig-1b throughout their lives, while the majority produce detectable Ig-1b sporadically, sometimes over a period of several weeks, the level of which eventually falls below detectability. Attempts to "cure" suppression by destroying the existent lymphoid population and forcing endogenous repopulation in chronically suppressed animals were unsuccessful. Furthermore, attempts to restore Ig-1b production by injection of cells from syngeneic Ig^a/Ig^b donors into irradiated, chronically suppressed recipients were also unsuccessful, although the same cell inocula, when injected into irradiated BALB/c (Ig^a/Ig^a) mice produced high levels of gamma globulin carrying the allotype. These results suggest that long-term allotype suppression resulting from perinatal exposure of offspring to specific anti-allotype antibody (anti-Ig-1b), is not due merely to an absence of Ig-1b-producing cells or their progenitors, but appears to be an active process, which dominates physiologically over normal production.     

Depression and body mass index, a u-shaped association

Background  

Results of studies concerning the association between obesity and depression are conflicting. Some find a positive association, some a negative association and some find no association at all. Most studies, however, examine a linear association between Body Mass Index (BMI) and depression. The present study investigates if a nonlinear (U-shaped) trend is preferable over a linear trend to describe the relationship between BMI and depression, which means that both underweight and obesity are associated with depression.     

Lumpectomy plus tamoxifen or anastrozole with or without whole breast irradiation in women with favorable early breast cancer

PURPOSE: In women with favorable early breast cancer treated by lumpectomy plus tamoxifen or anastrazole, it remains unclear whether whole breast radiotherapy is beneficial. METHODS AND MATERIAL: Between January 1996 and June 2004, the Austrian Breast and Colorectal Cancer Study Group (ABCSG) randomly assigned 869 women to receive breast radiotherapy +/- boost (n = 414) or not (n = 417) after breast-conserving surgery (ABCSG Study 8A). Favorable early breast cancer was specified as tumor size <3 cm, Grading 1 or 2, negative lymph nodes, positive estrogen and/or progesterone receptor status, and manageable by breast-conserving surgery. Breast radiotherapy was performed after lumpectomy with 2 tangential opposed breast fields with mean 50 Gy, plus boost in 71% of patients with mean 10 Gy, in a median of 6 weeks. The primary endpoint was local relapse-free survival; further endpoints were contralateral breast cancer, distant metastases, and disease-free and overall survival. The median follow-up was 53.8 months. RESULTS: The mean age was 66 years. Overall, there were 21 local relapses, with 2 relapses in the radiotherapy group (5-y rate 0.4%) vs. 19 in the no-radiotherapy group (5.1%), respectively (p = 0.0001, hazard ratio 10.2). Overall relapses occurred in 30 patients, with 7 events in the radiotherapy group (5-y rate 2.1%) vs. 23 events in the no-radiotherapy group (6.1%) (p = 0.002, hazard ratio 3.5). No significant differences were found for distant metastases and overall survival. CONCLUSION: Breast radiotherapy +/- boost in women with favorable early breast cancer after lumpectomy combined with tamoxifen/anastrazole leads to a significant reduction in local and overall relapse.     

Clinical experience with water-heated interstitial hyperthermia system

An orignal circulating hot water hyperthermia system for interstitial treatment has been constructed at the University Cliic for Radiotherapy and Radiobiology in Vienna, Austria. At the Institute of Oncology in Ljubljana, Slovenia, animal experiments as well as a few human treatments were done. Results obtained with 4×4 metal needle implants on rabbits and/or pigs thigh showed that a good temperature distribution inside the heated volume could be achieved. The homogeneity of temperature distribution obtained in human applications using plastic tubes was also acceptable. Although somewhat lower temperatures inside the treated volume were measured in human treatments, the minimum temperatures obtained were still on the cytotoxic level (over 42,5 °C). With some improvements using cooling system for the tumor surrounding zone the damage of the healthy tissue inside the treatment volume could be avoided.     

Unraveling B-1 progenitors

B-1 cells comprise a small percentage of the B lymphocytes that reside in multiple tissues in the mouse, including the peritoneal and pleural cavities. Functionally, B-1 cells participate in innate immunity by producing the majority of the natural IgM in serum, which protects against invading pathogens before the onset of the adaptive immune response. B-1 cells arise from fetal and neonatal progenitors and are distinct from the adult bone marrow progenitors that give rise to follicular and marginal zone B-2 cells. Recent studies have attempted to delineate the progenitors of B-1 cells from those of B-2 cells. Notably, the identification of CD45R(-/lo)CD19(+) B-1 progenitors and expression of two surface determinants, CD138 and major histocompatibility class II antigens, distinguish developing B-1 cells from B-2 cells.     

Qualitätssicherung in der Therapie chronischen Schmerzes Ergebnisse einer Arbeitsgruppe der DGSS zur psychologischen Diagnostik

Disability is a central aspect in the assessment of chronic pain patients. Disability questionnaires in German (developed or adapted) are examined and selected for different purposes. The “Funktionsfragebogen Hannover” and the “Pain Disability Index” are recommended for both research and clinicalapplication while the “Sickness Impact Profile” is suitable only for research purposes. Four different German questionnaires for the assessment of social interaction and communication in pain patients and their significant others are examined in part VII. There are some empirical data for three of them. Only the “Inventory of Familial Adaptability and Cohesion” has achieved a certain degree of empirical maturity. Further research and developmental activity in this area of pain assessment are urgently needed.     

Beneficial effects versus toxicity of medium-chain triacylglycerols in rats with NASH

BACKGROUND/AIMS: Replacing long-chain triacylglycerols (LCT) with medium-chain triacylglycerols (MCT) reduces alcohol-induced liver injury. Because of the similarity of the pathogenesis of alcohol-induced liver damage and non-alcoholic steatohepatitis (NASH), our aim was to assess whether MCT is also beneficial in NASH. METHODS: We used a rat NASH model in which corn oil (35% of total calories) was isocalorically replaced with MCT. RESULTS: Partial replacement of LCT did not ameliorate hepatic fat accumulation, 4-hydroxynonenal, collagen type I and its mRNA but it increased TNF-alpha and its mRNA (p<0.001). However, in rats given the high-fat diet restricted to 2/3 of the amount they were consuming, these adverse effects decreased, with and without MCT including less liver steatosis and lower triacylglycerols, but without beneficial effects of MCT. When 70% of the fat calories were replaced with MCT with no LCT remaining in the diet, no steatosis developed and hepatic TNF-alpha was low. When all MCT were given with carbohydrates (instead of LCT) hepatic TNF-alpha also decreased (p<0.001). CONCLUSIONS: MCT are not hepatotoxic, provided the diet contains no significant amount of LCT. Total replacement of dietary LCT with MCT fed ad libitum is beneficial whereas partial replacement becomes hepatotoxic, unless the dietary intake is restricted.