Procedural memory stimulation in Alzheimer''s disease: impact of a training programme

The operative results of 23 patients with a specific or unspecific spondylodiscitis were documented over 2 years after the focus of the inflammation had been eradicated, bone chip had been interposed and a CDH instrumentation had been performed by an anterior approach only. These outcomes were compared with the results of 32 patients in whom the focus had been removed and the defect had been filled with bone graft from an anterior approach, followed by stabilisation with CD instrumentation through an additional dorsal approach. In the cases where CDH instrumentation was applied, the range of fusion averaged 1.3 segments. This was clearly less extensive than in dorsoventral stabilisation, in which on average 3.5 segments were fused. In 47 of 55 cases mobilisation was achieved without orthesis. Eight months after the operations bony fusion could be observed radiologically in all patients. The mean preoperative kyphotic angle of the affected segments was 14.4 degrees, compared to 4 degrees after the operation. The mean loss of reposition was measured to be about 2.7 degrees in both groups. Average operation time and blood loss were about 50% higher in the patients treated dorsoventrally. We conclude that even in the case of florid spondylodiscitis, a short-range anterior fusion of the affected spinal segment may be performed by use of a stable-angle implant without an increased risk of infection-related loosening.     

Complete nucleotide sequence of HTLV-II isolate NRA: comparison of envelope sequence variation of HTLV-II isolates from U.S. blood donors and U.S. and Italian i.v. drug users

Seven cardiac electrophysiology stimulators from four manufacturers (Biotronik, Bloom, Digitimer and Medtronic) in common current use are reviewed. The stimulators differ in the features provided and the design adopted to achieve these features. The number of output channels ranges from one to four, the number of extra-stimuli available ranges from two to six, and these can be delivered as a variety of sequences. Some of the stimulators (Digitimer and Bloom) are modular while others (Biotronik and Medtronic 532 series) are of an integrated design comprising a single physical unit. The design of the Medtronic EP-2 has both integrated and modular characteristics. The features of the stimulators associated with input, output, control and the user interface are specifically reviewed. The features are also compared against the published recommendations of the American Heart Association. In addition, a summary of stimulator user comments from a number of electrophysiology centres is presented. All of the stimulators fulfil, or are close to fulfilling, basic electrophysiological requirements, but some provide more complex facilities such as would be required by specialist centres.     

Production and properties of micro‐porous glas bubble zinc and aluminium composites

Micro‐porous syntactic foams were produced by means of integration of glass bubbles into aluminium and zinc matrices. Preforms of glass bubbles were pressure infiltrated with the alloys AlSi9Cu9 ans ZnAl4Cu using squeeze casting. The preforms were sintered thermically without the use of bonding agents. Using the combination of different sintering steps syntactic foams with locally different densities could be produced. The mechanical properties of the foams were tested indicating a high compression strength of the foams and a very good compression energy absorption. Furthermore, corrosion behaviour and behaviour at higher temperatures were investigated.     

The role of cysteine residues of spinach ferredoxin-NADP+ reductase As assessed by site-directed mutagenesis

To investigate the functional role of the cysteine residues present in the spinach ferredoxin-NADP+ oxidoreductase, we individually replaced each of the five cysteine residues with serine using site-directed mutagenesis. All of the mutant reductases were correctly assembled in Escherichia coli except for the C42S mutant protein. C114S and C137S mutant enzymes apparently showed structural and kinetic properties very similar to those of the wild-type reductase. However, C272S and C132S mutations yielded enzymes with a decreased catalytic activity in the ferredoxin-dependent reaction (14 and 31% of the wild type, respectively). Whereas the C132S was fully competent in the diaphorase reaction, the C272S mutant flavoprotein showed a 35-fold reduction in catalytic efficiency with respect to the wild-type enzyme (0.4 versus 14.28 microM-1 s-1) due to a substantial decrease of kcat. NADP+ binding by the C272S mutant enzyme was apparently quantitatively the same (Kd = 37 microM) but qualitatively different, as shown by the differential spectrum. Stopped-flow experiments showed that the enzyme-FAD reduction rate was considerably decreased in the C272S mutant reductase, along with a much lower yield of the charge-transfer transient species. It is inferred from these data that the charge transfer (FAD-NADPH) between the reductase and NADPH is required for hydride transfer from the pyridine nucleotide to flavin to occur with a rate compatible with catalysis.     

In vitro model for the evaluation of toxicity and antinutritional effects of sulphites.

The food preservatives, sulphur dioxide and its salts, are known to present some toxic, mutagenic and antinutritional effects; in fact they interact with a number of nutrients, e.g. some vitamins, notably thiamine (Th) and folic acid (FA). The effect of different concentrations of sodium bisulphite in cell culture media has been studied in vitro on a human cell line, HEp-2, deriving from a carcinoma of the larynx. Moreover, the sulphites have been tested with different levels of Th and FA with the aim of elucidating how much the cellular response depended on either the anti-nutritional effect or the toxicity of sulphites. Cell growth has been taken as an index of cytotoxicity and measured both as total protein content and as colony-forming ability. With no Th and FA in the culture medium, a clear decrease of cell growth was observed either with or without addition of sodium bisulphite. A dose-dependent reduction of protein content was detected in cells treated with 10, 50, 100, 200, 250 or 500 microM sodium bisulphite. Moreover, when the cells were treated with 10 or 100 microM of this compound, the colony-forming ability was reduced both in number and colony size. As far as the interaction of the two vitamins with sodium bisulphite is concerned, when these nutrients were present in the medium at 0.5, 1.0, 1.5, 2.0 or 2.5 mg/l, a similar growth profile, determined from their concentration, was observed in treated and control cells, the growth levels being affected by the sodium bisulphite contents. At higher levels of Th and FA, the growth index was still increasing only in treated cells, this phenomenon being particularly evident in cultures treated with 200 microM sodium bisulphite. The colony-forming ability was reduced in controls but still increased in treated cells at the highest concentration of vitamins.     

Cancer risk and social inequalities in Italy

STUDY OBJECTIVE: To investigate social differences in cancer incidence in Turin, Italy in 1985-87. DESIGN: A cancer incidence follow up study of the turin population in relation to socioeconomic characteristics was performed through record linkage between the 1981 census and the cancer registry. A case-control study nested in the cohort was analysed, where cases were subjects with a new diagnosis of cancer in 1985-87 and controls were a sample of the Turin population, frequency matched by sex and age group. Incidence odd ratios (ORs) were calculated for social classes (defined by education, housing tenure, and socioeconomic group) using a logistic regression model. SETTING: The study population comprised subjects included in the 1981 Turin census (n approximately equal to 1,100,000) who were still alive, 20-69 years old, and were resident in Turin in the middle of study period. PARTICIPANTS: The analyses were based on 4215 male and 3451 female cases, and on 16,913 male and 13,838 female controls. MAIN RESULTS: Compared with the highest educational level, the men in the lowest one showed an OR > 2 for respiratory cancers; OR = 1.48 for stomach cancer; and ORs < 0.7 for skin, colorectal, and prostate cancers. Women with a primary school education were protected against colorectal (OR = 0.71), skin (OR = 0.59), and breast cancer (OR = 0.66) compared with university degree women, but were at risk for cancer of the cervix (OR = 2.33) and stomach cancer (OR = 2.84). The association between educational level (primary school v university) and lung cancer risk is negative for men (OR = 2.47) and positive for women (OR = 0.62), while the association with housing tenure is negative for both sexes (OR = 1.44). CONCLUSIONS: The socioeconomic distribution of some risk factors (for example smoking, alcohol, and diet) in Italy can partially explain the differences in respiratory and digestive cancers. "Unbalanced" health promotion interventions, targeted at social groups with the highest prevalences of risk factors, and national policies for increasing the level of education in the country may play an important role in reducing social differences in cancer risk.     

Active immunity against the CD4 receptor by using an antibody antigenized with residues 41-55 of the first extracellular domain

Using the process of "antibody antigenization," we engineered two antibody molecules carrying in the third complementarity-determining region of the heavy chain variable domain a 7-mer or a 15-mer peptide epitope of the first extracellular domain (D1) of human CD4 receptor--namely, Ser-Phe-Leu-Thr-Lys-Gly-Pro-Ser (SFLTKGPS; positions 42 through 49) and Gly-Ser-Phe-Leu-Thr-Lys-Gly-Pro-Ser-Lys-Leu-Asn-Asp-Arg-Ala (GSFLTKGPSKLNDRA; positions 41 through 55). These amino acid sequences are contained in the consensus binding site for the human immunodeficiency virus (HIV) on CD4 receptor. Both antigenized antibodies (AgAbs) bound recombinant gp120 and were recognized by a prototype monoclonal antibody to CD4 whose binding site is within amino acid residues 41-55. AgAbs were then used as immunogens in rabbits and mice to elicit a humoral response against CD4. Only the AgAb carrying the sequence 41GSFLTKGPSKLN-DRA55 induced a response against CD4. The induced antibodies showed specificity for the amino acid sequence of CD4 engineered in the AgAb molecule, were able to inhibit the formation of syncytia between human CD4+ T cells MOLT-3 and 8E5 (T cells that are constitutively infected with HIV), and stained human CD4+ CEM T cells. Four murine monoclonal antibodies were used to analyze the relationship between syncytia inhibition and CD4 binding at the single antibody level, and indicated that recognition of native CD4 is not an absolute requirement for inhibition of syncytia. This study demonstrates that antigenized antibodies can be used as immunogens to elicit site-specific and biologically active immunity to CD4. The importance of this approach as a general way to induce anti-receptor immunity and as a possible new measure to immunointervention in HIV infection is discussed.     

The Role of Cytoskeleton Revealed by Quartz Crystal Microbalance and Digital Holographic Microscopy

The connection between cytoskeleton alterations and diseases is well known and has stimulated research on cell mechanics, aiming to develop reliable biomarkers. In this study, we present results on rheological, adhesion, and morphological properties of primary rat cardiac fibroblasts, the cytoskeleton of which was altered by treatment with cytochalasin D (Cyt-D) and nocodazole (Noc), respectively. We used two complementary techniques: quartz crystal microbalance (QCM) and digital holographic microscopy (DHM). Qualitative data on cell viscoelasticity and adhesion changes at the cell–substrate near-interface layer were obtained with QCM, while DHM allowed the measurement of morphological changes due to the cytoskeletal alterations. A rapid effect of Cyt-D was observed, leading to a reduction in cell viscosity, loss of adhesion, and cell rounding, often followed by detachment from the surface. Noc treatment, instead, induced slower but continuous variations in the rheological behavior for four hours of treatment. The higher vibrational energy dissipation reflected the cell’s ability to maintain a stable attachment to the substrate, while a cytoskeletal rearrangement occurs. In fact, along with the complete disaggregation of microtubules at prolonged drug exposure, a compensatory effect of actin polymerization emerged, with increased stress fiber formation.