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).     

Restoration of X-ray and etoposide resistance, Ku-end binding activity and V(D) J recombination to the Chinese hamster sxi-3 mutant by a hamster Ku86 cDNA

Ku is a heterodimeric protein composed of 86 and 70 kDa subunits that binds preferentially to the double-stranded ends of DNA. Recent molecular characterization of ionizing-radiation sensitive (IRs) mutants belonging to the XRCC5 complementation group demonstrated the involvement of Ku in DNA double-strand break (DSB) repair and lymphoid V(D)J recombination. Here, we describe the isolation of a full-length hamster cDNA encoding the large subunit of the Ku heterodimer and demonstrate that the stable expression of this cDNA can functionally restore IR, Ku DNA end-binding activity and V(D)J recombination proficiency in the Chinese hamster IRs sxi-3 mutant. Moreover, we also demonstrate that sxi-3 cells are hypersensitive to etoposide, a DNA topoisomerase II inhibitor, and that resistance to this drug was restored by the Ku86 cDNA. These experiments suggest that a defect in the large subunit of the heterodimeric Ku protein is the sole factor responsible for the known defects of sxi-3 cells and our data of further support the role of Ku in DNA DSB repair and V(D)J recombination.     

The block to HIV-1 envelope glycoprotein-mediated membrane fusion in animal cells expressing human CD4 can be overcome by a human cell component(s)

Membrane fusion mediated by interaction of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein with the human CD4 molecule generally requires that the CD4 be expressed on a human cell. The failure of murine or simian cells expressing human CD4 to form syncytia upon mixing with cells expressing envelope glycoprotein could not be corrected by expression of both molecules at extremely high surface levels using vaccinia virus expression vectors. Video fluorescence microscopic analysis of fluorescent dye transfer between fusing cells indicated that the block occurred at the level of membrane fusion between individual pairs of cells. To gain insight into the basis for this fusion block, we tested the ability of fluorescent probe cells expressing envelope glycoprotein to fuse with transient animal x human hybrid giant cells expressing human CD4. The hybrid giant cells were generated either by low-pH-induced fusion of vaccinia-infected cells or by CD4/HIV-1 envelope glycoprotein-mediated cell fusion. We observed that envelope glycoprotein-expressing probe cells efficiently fused with CD4-expressing animal x human hybrid giant cells, independent of whether the CD4 was originally expressed on the animal or on the human cell. Fusion did not occur with CD4-expressing giant cells derived from animal cells alone. These results indicate that the fusion block is not due to dominant inhibitory components in the animal cell. Rather, they suggest that human cells contain an additional component(s) which, when transferred to the CD4-bearing animal cell, confers the ability to undergo membrane fusion mediated by the HIV-1 envelope glycoprotein.     

Management of lymphoproliferative disorders after cardiac transplantation

We conducted a retrospective study of 516 cardiac recipients who underwent transplantation between April 1983 and April 1992, 19 of whom had development of post-transplantation lymphoproliferative disorders (PTLDs). These 19 patients presented with involvement of lung (5), gastrointestinal tract (5), disseminated disease (6), and adenoids and lymph nodes (3). B-cell proliferations ranging from an atypical hyperplasia to malignant lymphoma developed in 18 patients, and mixed cellularity Hodgkin's disease developed in 1 patient. The 19 patients with PTLD displayed a predominance of both women and cardiomyopathy as the indication for transplantation when compared with two separate control populations. No correlation was found between demographic criteria analyzed and (1) early versus late diagnosis of PTLD after transplantation, (2) the site of PTLD involvement, or (3) the histopathologic category of the PTLD lesion. Patients with gastrointestinal tract and lung PTLD involvement enjoyed an improved survival after both transplantation and PTLD diagnosis when compared with patients with PTLD involvement of all other extranodal sites. We report a high incidence of PTLD involving the lung and gastrointestinal tract in our cohort study. These sites of involvement responded better to a reduction in immunosuppression than did the other extranodal sites of involvement.     

Thoracoscopic pleural tent

Lung volume reduction has been performed in patients with advanced emphysema to relieve dyspnea and improve exercise tolerance. Median sternotomy and video-assisted thoracoscopy have been proposed as equally adequate approaches; however, prolonged postoperative air leakage is the most prevalent complication in all series. For this reason, on the basis of the experience achieved with the median sternotomy approach, buttressing of the suture line with different materials and techniques for space reduction have been proposed. We describe a technique to create a pleural tent after thoracoscopic volume reduction. The thoracoscopic creation of a pleural tent is feasible and results in a duration of postoperative air leaks and hospital stays similar to that achieved with stapler line buttressing.     

Regulation of the proliferative potential of cord blood long-term culture-initiating cells (LTC-IC) by different stromal cell lines: implications for LTC-IC measurement

BACKGROUND AND OBJECTIVE: Long-term culture-initiating cells (LTC-IC) are the best available approximation to an in vitro assay of stem cells in humans although they still represent a heterogeneous population in terms of proliferative capacity and sensitivity to different growth factors. Human umbilical cord blood (CB) is rich in hemopoietic progenitor cells, as measured by clonogenic assays and contains stem cells capable of reconstituting the marrow after ablation in clinical transplantation. We evaluated the influence of culture conditions on the in vitro behavior of LTC-IC from CB. DESIGN AND METHODS: LTC-IC were evaluated in long-term cultures, comparing two types of murine stromal cell lines: M2-10B4 and M2-10B4 transfected with cDNAs for human G-CSF and IL-3. RESULTS: Two and five fold higher numbers of terminally differentiated cells were produced during nine weeks of culture of CB mononuclear or CD34+ cells respectively, in cultures containing a M2-10B4 IL-3 G-CSF cell line compared to cultures containing the parental cell line. Likewise, a higher number of colony-forming cells (CFC) were detected in the supernatant of cultures with the transfected cell line. In contrast, the number of CFC generated within the stromal layer, after 5 or 9 weeks of culture, was significantly higher in cultures on M2-10B4 cells than those on M2-10B4 IL-3 G-CSF. INTERPRETATION AND CONCLUSIONS: Our results show that the proliferative capacity of CB LTC-IC can be strongly influenced by culture conditions and that the frequency of LTC-IC estimated using these cell lines as stromal support is not identical.