Immunoactive effects of various mistletoe lectin-1 dosages in mammary carcinoma patients

Cellular aspects of the immunomodulating activity of a proprietary mistletoe extract (Eurixor) standardized for mistletoe lectin-1 (ML-1) were investigated in patients suffering from mammary carcinoma (n = 20). Regular subcutaneous injections of the different dosages (0.5 and 1.0 ng ML-1/kg body weight, twice a week, for 5 weeks) yielded statistically significant increases of defined peripheral blood lymphocyte subsets (helper T-cells, natural killer (NK)-cells) which are generally believed to be involved in antitumor activity. Moreover, administration of either ML-1 concentration resulted in enhanced expression of activation markers such as interleukin-2 receptors and HLA/DR-antigens on peripheral blood T-lymphocytes. This study suggests that regular subcutaneous administration of both ML-1 concentrations (0.5 and 1.0 ng/kg body weight) can efficiently stimulate the cellular immune system of cancer patients.     

Reactivity of fibrinogen and fibrinopeptide A containing fibrinogen fragments with antisera to fibrinopeptide A

Two antisera used in the radioimmunoassay for human fibrinopeptide A (FPA) which appear to have different immunochemical specificities have been tested for cross-reactivity with fibrinogen and with three fragments of fibrinogen which contain the FPA sequence. These fragments were the three-chain, NH2-terminal disulfide knot (N-DSK) produced by CNBr cleavage of fibrinogen, the reduced, carboxymethyl Aalpha chain portion of the N-DSK, and fragment E produced by plasmin digestion of fibrinogen. One antiserum (R-2) showed high specificity for free FPA and less than 2% cross-reactivity with fibrinogen or the FPA-containing fragments. The other antiserum (R-33) possessed a much higher degree of cross-reactivity with the FPA-containing fragments. Synthetic and native fibrinopeptides were found to be indistinguishable in the assay system with either antiserum. As a result of these studies, an hypothesis has been developed concerning the nature of the antigenic determinants on FPA which favor measurement of free FPA and limit cross-reactivity with larger, FPA-containing peptides.     

Changes in psychiatric admission MMPI profiles over a period of 15 to 20 years

An attempt was made to compare admission MMPI profiles of a matched sample of psychiatric inpatients over a 15- to 20-year period. For both males and females, significant decreases in MMPI indices of psychopathology occurred. Possible reasons for this decrease are presented.     

Co-existing abdominal aortic aneurysm and intra-abdominal malignancy: reflections on the order of treatment

BACKGROUND: The management of simultaneously occurring abdominal aortic aneurysm and intra-abdominal malignancy is controversial. It is unclear whether to treat the aneurysm first or the malignancy, or both simultaneously. If the malignancy is resected first there is a risk of postoperative rupture of the aneurysm. If simultaneous surgery is performed there is a risk of prosthetic graft infection from contamination by gastrointestinal or urinary tract contents. METHODS: Relevant papers from 1960 to 1996, identified from Medline and manual searching, were reviewed. RESULTS AND CONCLUSION: The literature supports the conclusion that the lesion of greater priority is that posing the greater threat to the patient; this is usually the aneurysm, especially if it is over 6 cm in diameter. For renal malignancies simultaneous surgery is the treatment of choice, but for bladder cancer the best management is unclear. Large aneurysms should usually be resected in preference to colorectal cancer unless the cancer is locally advanced, perforated or likely to result in early intestinal obstruction. If both lesions are complicated there may be a case for simultaneous treatment.     

Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis

The proapoptotic Bax protein induces cell death by acting on mitochondria. Bax binds to the permeability transition pore complex (PTPC), a composite proteaceous channel that is involved in the regulation of mitochondrial membrane permeability. Immunodepletion of Bax from PTPC or purification of PTPC from Bax-deficient mice yielded a PTPC that could not permeabilize membranes in response to atractyloside, a proapoptotic ligand of the adenine nucleotide translocator (ANT). Bax and ANT coimmunoprecipitated and interacted in the yeast two-hybrid system. Ectopic expression of Bax induced cell death in wild-type but not in ANT-deficient yeast. Recombinant Bax and purified ANT, but neither of them alone, efficiently formed atractyloside-responsive channels in artificial membranes. Hence, the proapoptotic molecule Bax and the constitutive mitochondrial protein ANT cooperate within the PTPC to increase mitochondrial membrane permeability and to trigger cell death.     

Trophoblast class I major histocompatibility complex (MHC) products are resistant to rapid degradation imposed by the human cytomegalovirus (HCMV) gene products US2 and US11

The ryanodine receptor Ca2+ channel (RyRC) constitutes the Ca2+-release pathway in sarcoplasmic reticulum (SR) of cardiac muscle. A direct mechanical and a Ca2+-triggered mechanism (Ca2+-induced Ca2+ release) have been proposed to explain the in situ activation of Ca2+ release in cardiac muscle. A variety of chemical oxidants have been shown to activate RyRC; however, the role of modification induced by oxygen-derived free radicals in pathological states of the muscle remains to be elucidated. It has been hypothesized that oxygen-derived free radicals initiate Ca2+-mediated functional changes in or damage to cardiac muscle by acting on the SR and promoting an increase in Ca2+ release. We confirmed that superoxide anion radical (O2-) generated from hypoxanthine-xanthine oxidase reaction decreases calmodulin content and increases 45Ca2+ efflux from the heavy fraction of canine cardiac SR vesicles; hypoxanthine-xanthine oxidase also decreases Ca2+ free within the intravesicular space of the SR with no effect on Ca2+-ATPase activity. Current fluctuations through single Ca2+-release channels have been monitored after incorporation into planar phospholipid bilayers. We demonstrate that activation of the channel by O2- is dependent of the presence of calmodulin and identified calmodulin as a functional mediator of O2--triggered Ca2+ release through the RyRC. For the first time, we show that O2- stimulates Ca2+ release from heavy SR vesicles and suggest the importance of accessory proteins such as calmodulin in modulating the effect of O2-. The decreased calmodulin content induced by oxygen-derived free radicals, especially O2-, is a likely mechanism of accumulation of cytosolic Ca2+ (due to increased Ca2+ release from SR) after reperfusion of the ischemic heart.