Differential mortality: some comparisons between England and Wales, Finland and France, based on inequality measures

Inequalities in mortality between social classes or socioeconomic groups were compared in three European countries, using similar sources of data from large national cohort studies. People registered at a census in 1971 (1975 for France) or a sample of them, were followed until 1980 or 1981. The Gini coefficient, a measure widely used in economics, allowed the comparison of various situations involving different numbers and group sizes. It was applied to age groups 35-44, and 45-54 for men only. According to this measure, inequalities were of the same order in England and Wales and Finland, and greater in France. Differences between the three countries concerning the principal causes of death leading to inequalities were cardiovascular diseases in England and Wales, accidents and cardiovascular diseases in Finland, and cancer and cirrhosis in France.     

Increase in membrane uptake of long-chain fatty acids early during preadipocyte differentiation.

An increase in early rates of oleate uptake, which reflected fatty acid (FA) entry into the cells, was apparent 2-3 days after confluence of differentiating BFC-1 preadipocytes. The increase was measured in cells kept without glucose and with arsenate, where greater than 95% of intracellular radioactivity was recovered as free unesterified oleate. Uptake of retinoic acid, a molecule structurally similar to long-chain FA, remained unaltered during cell differentiation. Increase in oleate transport was related to increase in transport Vmax (determined under arsenate treatment) from 0.2 to 2 nmol/min per 10(6) cells, whereas Km remained unchanged (2 x 10(-7) M). Oleate transport was maximal at about day 6 after cell confluence (day 0), as FA metabolism (incorporation into lipids) began to gradually increase. The increase in transport preceded induction of mRNAs for both cytosolic FA-binding protein, which appeared at day 6, and for the FA synthase, which appeared at day 10. Data indicated that increases in activities of FA transport and of lipoprotein lipase, early during cell differentiation, favored increased availability of exogenous FA at a stage when endogenous FA synthesis is limited. This result would promote FA esterification and lipid deposition by supplying a rate-limiting substrate. Furthermore, oleate addition to BFC-1 preadipocytes at confluence potentiated the effect of dexamethasone in inducing mRNA for cytosolic FA-binding protein. In adipocytes, FA from exogenous or endogenous sources was necessary to maintain levels of cytosolic FA-binding protein mRNA. Thus, the increase in FA availability might contribute to, or modulate, induction of proteins necessary for preadipocyte differentiation.     

Biocompatibility studies of the Anaconda stent-graft and observations of nitinol corrosion resistance.

PURPOSE: To validate the deployment, in vivo performance, biostability, and healing capacity of the Anaconda self-expanding endoprosthesis in a canine aortic aneurysm model. METHODS: Aneurysms were surgically created in 12 dogs by sewing a woven polyester patch onto the anterior side of the thoracic or abdominal aorta. Anaconda prostheses were implanted transfemorally for prescheduled periods (1 or 3 months). Aneurysm exclusion and stent-graft patency were monitored angiographically. Healing was assessed with histological analysis and scanning electron microscopy (SEM). Textile analysis determined the physical and chemical stability of the woven polyester material, while the biostability of the nitinol wires was evaluated with SEM and spectroscopy. RESULTS: All prostheses were intact at explantation. After 1 month, endothelial-like cells were migrating in a discontinuous manner both proximally and distally over the internal collagenous pannus at the device-host boundary. After 3 months, endothelialization had reached the midsections of the devices, with a thicker collagenous internal capsule. Patches of endothelial-like cells were sharing the luminal surface with thrombotic deposits. However, the wall of the device at the level of the aneurysm was generally poorly healed, with multiple thrombi scattered irregularly over the luminal surface. The polyester fabric was intact except for some filaments that were ruptured adjacent to the sutures and some abrasion caused by the nitinol wires. No evidence of corrosion was found on the nitinol stents. CONCLUSIONS: This Anaconda stent-graft has demonstrated its ability to exclude arterial aneurysms. The device used in this study was an experimental prototype, and the manufacturer has incorporated new immobilization features into the model for clinical use. The constituent materials appear to be suitable in terms of biocompatibility, biofunctionality, and short-term durability.     

Comparative effects of quinolones on human mononuclear leucocyte functions

The effects of three quinoline derivatives--pefloxacin, ciprofloxacin and ofloxacin--were investigated in mitogen-stimulated human peripheral blood mononuclear leucocytes (MNL). At concentrations of 50 mg/l or more, pefloxacin, ciprofloxacin or ofloxacin significantly inhibited MNL proliferation in response to phytohaemagglutinin. This inhibition was more marked with ciprofloxacin than pefloxacin or ofloxacin. To determine the possible mechanism(s) involved in the inhibition of MNL proliferation following exposure to pefloxacin, ciprofloxacin or ofloxacin, we assessed (1) interleukin-1 (IL-1) activity in supernatants from monocytes treated with the quinolones and (2) the effects of 2-mercaptoethanol (2-ME) a thiol compound which acts as an antioxidant agent and the effect of indomethacin (INDO) an inhibitor of prostaglandin E2 synthesis. 2-ME and INDO did not prevent the decrease in the proliferation. IL-1 activity was shown to be decreased for the same range of antibiotic concentrations as observed for the inhibition of MNL proliferation. Cellular viability of the MNL or monocytes was not modified by any of the quinolones at the concentrations tested. Taken together, these results suggest that pefloxacin, ciprofloxacin and ofloxacin act as immunomodulators. The mechanism involved with the cascade of events that leads to the lymphocyte proliferation and the clinical relevance need further investigation.     

Differential expression of extracellular matrix metalloproteinase inducer (CD147) in normal and ulcerated corneas: role in epithelio-stromal interactions and matrix metalloproteinase induction

Extracellular matrix metalloproteinase inducer (EMMPRIN) was originally identified on the tumor cell surface as an inducer of matrix metalloproteinase (MMP) production in neighboring fibroblasts. Here we demonstrate a role for EMMPRIN in MMP induction during corneal wound healing. MMP and EMMPRIN expression was analyzed in normal and ulcerated human corneas, as well as in corneal epithelial and stromal cells in culture using confocal microscopy, zymography, immunoblots, and real-time polymerase chain reaction. In normal cornea EMMPRIN was predominantly expressed in the epithelium but was markedly induced in the anterior stroma of ulcerated corneas. This coincided with MMP-2 induction that co-localized with EMMPRIN at the epithelio-stromal boundary. The role of epithelial-stromal interaction in MMP induction was investigated in an in vitro co-culture system and demonstrated an induction and co-localization of EMMPRIN and MMP-2 in the fibroblasts at the interface with epithelial cells. Direct contact of fibroblasts with EMMPRIN-containing purified epithelial cell membranes also induced MMP-1, MMP-2, and EMMPRIN and this was inhibited by a blocking anti-EMMPRIN antibody, suggesting that EMMPRIN was primarily responsible for this induction. These findings, and the up-regulation of EMMPRIN by epidermal growth factor and transforming growth factor-beta, demonstrate a role for EMMPRIN in wound healing and suggest that sustained local up-regulation of EMMPRIN and MMPs in chronic situations in which healing is delayed may lead to excessive matrix degradation and corneal melts.     

Hfq-dependent regulation of OmpA synthesis is mediated by an antisense RNA

This paper shows that the small RNA MicA (previously SraD) is an antisense regulator of ompA in Escherichia coli. MicA accumulates upon entry into stationary phase and down-regulates the level of ompA mRNA. Regulation of ompA (outer membrane protein A), previously attributed to Hfq/mRNA binding, is lost upon deletion of the micA gene, whereas overexpression of MicA inhibits the synthesis of OmpA. In vitro, MicA binds to the ompA mRNA leader. Enzymatic and chemical probing was used to map the structures of MicA, the ompA mRNA leader, and the complex formed upon binding. MicA binding generates a footprint across the ompA Shine-Dalgarno sequence, consistent with a 12 + 4 base-pair interaction, which is additionally supported by the effect of mutations in vivo and by bioinformatics analysis of enterobacterial micA/ompA homolog sequences. MicA is conserved in many enterobacteria, as is its ompA target site. In vitro toeprinting confirmed that binding of MicA specifically interferes with ribosome binding. We propose that MicA, when present at high levels, blocks ribosome binding at the ompA translation start site, which-in line with previous work-secondarily facilitates RNase E cleavage and subsequent mRNA decay. MicA requires the presence of the Hfq protein, although the mechanistic basis for this remains unclear.     

Human epithelial thymic tumours: heterogeneity in immunostaining of epithelial cell markers and thymic hormones.

Different hormones (thymulin, thymosin alpha 1, vasopressin), antigenic markers of cortical and subcapsular/medullary thymic areas and tumour associated antigens were studied on paraffin or frozen section and cultures of human epithelial thymic tumours ('thymomas'). Thymulin, thymosin alpha 1 and for the first time vasopressin are found in most tumours. The epithelial cells of five 'thymomas' had markers of both cortical (TE3) and subcapsular/medullary thymic regions (A2B5 and/or TE4 and/or anti-p19). Leu-7, a marker of subcapsular epithelial cells was positive only in two tumours. The histological classification into cortical and medullary tumours does not correspond to our immunofluorescence results. The presence of these markers does not support the theory of different embryologic origin of the cortical and subcapsular/medullary epithelial cells. Transferrin receptors were detected on only some epithelial cells of thymic 'carcinomas'. Adenocarcinoma related antigen and carcino embryonic antigen only stained a few epithelial cells of all the tumours. There is no expected correlation between the presence of epidermal growth factor receptors on cell membranes and the number of proliferative cells stained by the anti-Ki67 antibodies. Immunostainings were heterogeneous according to the epithelial thymic tumours, independent of histological classification and not yet useful for prognosis.     

Immunoreactivity of aqueous extracts of rat and mouse tissue with anti-thymosin alpha 1, anti-bovine thymopoietin and anti-thymulin antibodies. Studies using immunoblotting

Anti-thymosin alpha 1 monoclonal antibodies recognized, on immunoblots, 1 to 2 bands corresponding to molecules of 34 and 35 Kd when using aqueous extracts of thymus, spleen, kidney, liver, brain, pituitary and adrenal glands from rats or mice. Anti-bovine thymopoietin polyclonal antibodies, in the same conditions, labelled analogous 34, 35 and 35.5 Kd molecules in brain and thymus extracts but also a 40 Kd molecules in thymus and a 90 Kd in brain extracts. Anti-synthetic thymulin monoclonal antibodies recognized irregularly and poorly a 52 Kd molecule from thymus and brain extracts. These results suggest that thymopoietin, thymulin and specially Thymosin alpha 1 are first synthesized in large precursors. Finally, other organs seem capable of synthesizing thymosin alpha 1 and probably thymopoietin, but for thymulin, the results are too irregular to conclude.     

Cloning and expression of surface antigens from occult chronic hepatitis B virus infections and their recognition by commercial detection assays

Occult hepatitis B virus (HBV) infections show little or no serological markers of viral infection, including the absence of hepatitis B surface antigen (HBsAg) which is the main marker of ongoing HBV infection. Such infections can be important in the context of blood and/or organ donations. To study whether mutations contribute to HBsAg seronegativity, S gene sequences from such patients were amplified and cloned. Sequencing revealed 12 clones from seven different patients which contained potentially important mutations. The sequences were subcloned into an expression vector and mutant HBsAgs were expressed in cell culture. The capacity of three HBsAg detection assays to recognise the mutant HBsAgs was studied. Three categories were found: mutant HBsAgs that are not recognised by the assays, those that are recognised as well as wild-type (WT) antigen and an intermediate category where detection of the mutant HBsAgs is reduced with respect to WT. Most of the isolates fall into the second category. Mutations can therefore contribute to HBsAg seronegativity in occult HBV infections, but in most cases the explanation is probably the low level of viral replication.