Tripe palms: a cutaneous paraneoplastic syndrome

Tripe palms is a cutaneous paraneoplastic syndrome. We report a case of tripe palms in a 71-year-old man with non-small cell lung cancer. Approximately 90% of patients with tripe palms have an associated cancer, most commonly involving the lung or the stomach. Any patient with tripe palms must have a complete cancer workup, especially for lung and stomach cancer.     

Electron transfer by domain movement in cytochrome bc1

The cytochrome bc1 is one of the three major respiratory enzyme complexes residing in the inner mitochondrial membrane. Cytochrome bc1 transfers electrons from ubiquinol to cytochrome c and uses the energy thus released to form an electrochemical gradient across the inner membrane. Our X-ray crystal structures of the complex from chicken, cow and rabbit in both the presence and absence of inhibitors of quinone oxidation, reveal two different locations for the extrinsic domain of one component of the enzyme, an iron-sulphur protein. One location is close enough to the supposed quinol oxidation site to allow reduction of the Fe-S protein by ubiquinol. The other site is close enough to cytochrome c1 to allow oxidation of the Fe-S protein by the cytochrome. As neither location will allow both reactions to proceed at a suitable rate, the reaction mechanism must involve movement of the extrinsic domain of the Fe-S component in order to shuttle electrons from ubiquinol to cytochrome c1. Such a mechanism has not previously been observed in redox protein complexes.     

Evaluation of a new enzyme immunoassay for Clostridium difficile toxin A

AIM: To evaluate a new enzyme immunoassay (EIA) method for detection of Clostridium difficile toxin by comparing it to cytotoxicity assay. To investigate the nature of false negative and false positive EIA results by evaluating clinical and therapeutic parameters. METHODS: 737 consecutive diarrhoeal specimens collected from patients clinically suspected of having C difficile colitis were tested for the presence of C difficile toxin by EIA for toxin A and by cytotoxicity assay. Clinical data were evaluated in all cases positive by either method. RESULTS: With the cytotoxicity assay as a gold standard, the specificity of EIA for toxin detection was 99.3% and the sensitivity was 62.2%. No false negative EIA specimens were obtained from patients already being treated for C difficile colitis. Among patients with cytotoxicity positive specimens, those with EIA positive samples had no clinical features distinguishing them from patients with EIA negative samples. CONCLUSIONS: Although specific, the new EIA method directed against toxin A lacks sensitivity compared to cytotoxicity. False negative EIA tests are not associated with concurrent treatment for C difficile colitis nor with any specific clinical features examined in our study.     

Eimeria acervulina: influence of corticosterone-induced immunosuppression on oocyst shedding and production characteristics in broilers, and correlation with a computer simulation model

An experiment was conducted to investigate the effects of immune responsiveness on excretion of oocysts after E. acervulina infection and subsequent effects on production characteristics of broilers (Gallus domesticus). These effects were determined in broilers repeatedly infected with 2.85 x 10(3) oocysts of E. acervulina and treated with various dosages of corticosterone in the diet (0, 10, 20 and 30 p.p.m.). Corticosterone treatment did not have an effect on the peak oocyst excretion, although it was administered from 4 days before initial infection. The number of oocysts excreted shortly after the peak and the length of the excretion period were increased in corticosterone-treated groups. The absence of a difference in peak oocyst excretion was ascribed to the existence of a time-lag between first contact with the parasite and rate of development of protective immunity. In a recently developed computer simulation model this period was assumed to be 5 days. Assuming that immunosuppression, through corticosterone, is only effective when protective immunity is in operation, the results indicate a time-lag of at least a few days, which supports the inclusion of such a time-lag in the computer simulation model. General immunosuppressive effects of the corticosterone treatment, monitored by antibodies and mitogen-induced lymphocyte stimulation confirmed that immunosuppression occurred shortly after medication started. Infection did not have a significant influence on production characteristics in animals without dietary corticosterone. However, with increasing corticosterone levels the negative effects of infection on production also increased.     

A 6-year clinical assessment of electronic facial thermography

The authors briefly report their experience regarding the opportunities offered by the use of current ultrasound methods in carotid surgery. They describe: a system for the quantification of athcromasic plaque used to monitor non-operated patients over time; ultrasound methods used to analyse the carotid wall to establish whether it can be utilised as an index of vascular aggression in hypertension, diabetes and atherosclerosis; the use of transcranial Doppler; criteria for the definition of high risk plaque; the applications of eco-color Doppler. The paper also illustrates a new pathology identified by the authors, defined as primary intimal fibrous hyperplasia, and the evolution of the carotid wall after endarterectomy. The structural characteristics of primary hyperplasia can only be shown using ultrasound given that arteriography cannot distinguish it from atheromatic stenosis. After endarterectomy the carotid wall is subject to hematic and hemodynamic stimuli which determine the type of evolution of the wall itself. The authors therefore examine the myointimal reaction, myointimal hyperplasia, early restenosis and late restenosis as different facets of the same phenomenon.     

Immune recognition of viral antigens

The response exhibited by the immune system to viral and other foreign antigens consists of antibody-mediated and T cell-mediated immunity. Structural and molecular biological studies have shown that the antibody response is tailored to provide exquisite specificity by generating binding pockets that are complementary in shape as well as in charge to the antigen. On the other hand, the cellular response uses T-cell receptors (TCRs) and the major histocompatibility complex (MHC) antigens. Structural information on the TCRs is not yet available, but the crystal structures of several MHC class I molecules have shown how one MHC molecule can bind many different peptide sequences that share only the common anchor residue positions that determine allele specificity. MHC class I interactions with the peptide backbone at the N and C termini explain the high specificity of the binding groove for peptide ligands and suggest a universal mode of recognition for peptides to MHC class I molecules. Peptide-MHC class II interactions are less well understood, although recent structural work has shown important differences in the binding clefts of MHC class I and II that lead to longer peptides being bound to class II molecules. Detailed analysis at the molecular level has indicated that conformational changes in both antibodies and MHC molecules occur upon antigen binding.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aminopeptidases in cells of non-Hodgkin's lymphoma of varying degrees of malignancy and in lymphogranulomatosis

26 cases of lymphoproliferative diseases were studied: 8 cases of reactive follicular hyperplasia (RFH), 11 cases of non-Hodgkin's malignant lymphomas (NML), 7 cases of lymphogranulomatosis (LGM). Only gamma-glutamyl transpeptidase (GGT) was found in lymphoid cells of B- and T-dependent areas of lymph nodes with reactive changes as well as in tumor cells of NML and LGM. GGT activity was more pronounced in NML of high-grade malignancy (centroblast and immunoblast) as compared to lymphomas of lower grade of malignancy (lymphocytic, centroblast-centrocytic and in Lennert lymphoma). GGT activity in cells of Hodgkin and Berezovsky-Sterberg in some cases of LGM was high, in others low. Significant differences in GGT activity between RFH and follicular centroblast-centrocytic lymphoma were not found. Activity of aminopeptidase M was observed in histiocytes, fibroblasts, vessels and areas of connective tissue growth. Aminopeptidase A activity was observed in vessels only. Activity of dipeptidyl(amino)peptidase IV was observed in some lymphoid cells in RFH, NML and LGM. Thus, GGT activity may be considered as a differential-diagnostic marker in separating NML of high and low degree of malignancy and this may presume a different sensitivity to the therapy.     

Synthesis, estrogen receptor binding, and tissue distribution of a new iodovinylestradiol derivative (17alpha,20E)-21-[123I]Iodo-11beta-nitrato-19-norp regna-1,3,5 (10),20-tetraene-3,17-diol (E-[123I]NIVE)

We have synthesized and evaluated E-11beta-nitrato-17alpha-iodovinylestradiol (E-NIVE; E-3c) and its 123I-labelled form, as a new potential radioligand for imaging of estrogen receptor (ER)-positive human breast tumors. E-[123I]NIVE was prepared by stereospecific iododestannylation of the E-tri-n-butylstannylvinyl precursor (E-2c), obtained from reaction of 11beta-nitrato-estrone (8) with E-tributylstannylvinyllithium. In competitive binding studies, E-NIVE proved to have high binding affinity for both the rat and the human ER (Ki 280-730 pM), without significant binding to human sex hormone binding globulin. Distribution studies in normal and mammary tumor-bearing rats showed specific ER-mediated uptake of E-[123I]NIVE in the estrogen target tissues, i.e., uterus, ovaries, pituitary, and hypothalamus, but not in the mammary tumors. Selective retention in these target tissues, including tumor tissue, resulted in significant increases over time for the target tissue-to-muscle uptake ratios, but not for the target tissue-to-fat uptake ratios. The tumor-to-fat uptake ratio even appeared constantly below 1. In the primary estrogen target tissues, E-[123I]NIVE displayed high specific ER-mediated uptake and retention, which resulted in moderate target-to-nontarget tissue uptake ratios. In contrast, in tumor tissue, E-[123I]NIVE uptake appeared to be rather low and not ER-specific. As a consequence, E-[123I]NIVE appears to be a less favorable radioligand for ER imaging in breast cancer than the previously studied stereoisomers of 11beta-methoxy-17alpha-[123I]iodovinylestradiol (E- and Z-[123I]MIVE; [123I]E- and [123I]Z-3b).