Ulcero-multilating acropathy

A case of a 46 years old male suffering from chronic sensory neuropathy is reported. The symptoms consisted of superficial and deep sensory disturbances, and bilateral trophic plantar ulcerations with osteolysis, resulting in a deformity of the feet. There was an increased sweating of the distal portions of the four limbs, and a delayed adaptation of blood pressure and heart frequency to postural changes. CSF aminoacids were all increased except taurine, which was markedly descreased. An increased blood flow in lower extremities was demonstrated angiographically. The possibilities of pharmacological and surgical treatment raised by the hemodynamic hypothesis of BUREAU and BARRIERE (1957) are discussed.     

Finite difference methods for the analysis of integrated optical waveguides

A finite difference method based on a Crank-Nicolson discretisation procedure has been implemented and applied to the analysis of propagation of optical beams in dielectric waveguides. It is based on a new formula which takes into account the correct boundary conditions. Comparisons with the well known BPM technique show a definite improvement in computer time saving, accuracy and ease of use.<>     

Differential susceptibility to HIV-GP120-sensitized apoptosis in CD4+ T-cell clones with different T-helper phenotypes: role of CD95/CD95L interactions

The susceptibility of Th1 and Th2 cell clones to apoptosis following HIV-gp120/CD4 cross-linking and TCR activation was investigated. We show that only Th1 clones are susceptible to HIV-gp120-sensitized apoptosis, although both types of clones express similar levels of CD4 and bind similar amounts of recombinant gp120. Both types of clones, however, undergo apoptosis induced by CD95 cross-linking with agonistic monoclonal antibody (MoAb). Apoptosis induced by gp120 in the Th1 clones is inhibited by either an anti-CD95 neutralizing MoAb or an anti-CD95L neutralizing MoAb as well as by a specific interleukin-1 beta converting enzyme (ICE) inhibitor. When triggered to apoptosis by gp120, Th1 but not Th2 clones express both cell-associated and soluble CD95L. The CD95L produced by Th1 clones induces cell death, inhibitable by anti-CD95 neutralizing MoAb, of CD95 positive Jurkat cells. These data suggest that, like activation-induced apoptosis, HIV-gp120 sensitized apoptosis in Th1 clones occurs via CD95/CD95L interaction and that lack or insufficient production of CD95L is responsible, at least in part, for the resistance of Th2 clones to such apoptosis.     

Human melanoma-reactive CD4+ and CD8+ CTL clones resist Fas ligand-induced apoptosis and use Fas/Fas ligand-independent mechanisms for tumor killing

Tumor cells have been shown recently to escape immune recognition by developing resistance to Fas-mediated apoptosis and acquiring expression of Fas ligand (FasL) molecule that they may use for eliminating activated Fas+ lymphocytes. In this study, we report that tumor-specific T lymphocytes isolated from tumor lesions by repeated in vitro TCR stimulation with relevant Ags (mostly represented by normal self proteins, such as MART-1/Melan A and gp100) can develop strategies for overcoming these escape mechanisms. Melanoma cells (and normal melanocytes) express heterogeneous levels of Fas molecule, but they result homogeneously resistant to Fas-induced apoptosis. However, CD4+ and CD8+ CTL clones kill melanoma cells through Fas/FasL-independent, granule-dependent lytic pathway. In these lymphocytes, Ag/MHC complex interaction with TCR does not lead to functional involvement of FasL, triggered, on the contrary, by T cell activation with nonspecific stimuli such as PMA/ionomycin. Additionally, melanoma cells express significant levels of FasL (detectable on the cell surface only after treatment with metalloprotease inhibitors), although to a lesser extent than professional immune cells such as Thl clones. Nevertheless, antimelanoma CTL clones resist apoptosis mediated by FasL either in soluble form or expressed by Thl lymphocytes or FasL+ melanoma cells. These results demonstrate that CD4+ and CD8+ antimelanoma T cell clones can be protected against Fas-dependent apoptosis, and thus be useful reagents of immunotherapeutic strategies aimed to potentiate tumor-specific T cell responses.     

Single turnover mechanism of a trypsin-reactor with high enzyme concentration

PFGCN20 is a member of the ATP-binding cassette family of proteins that is closely related to the yeast translational regulator Gcn20p. We have generated a polyclonal antibody against the N-terminal region of PFGCN20 and studied the cellular localization of PFGCN20 throughout the erythrocytic life cycle of Plasmodium falciparum. PFGCN20 was found to be present at all stages and a pronounced export of PFGCN20 into the erythrocyte was observed in the trophozoite and schizont stages. In the indirect immunofluorescence assay, PFGCN20 was found to display significant colocalization with antigens detected by the monoclonal antibody 41E11. In contrast, there was only a minimal overlap of PFGCN20 localization with EMP2 and HRP2. Immunoelectron microscopy demonstrated a pronounced accumulation of PFGCN20 in the lumen of the parasitophorous vacuole and deconvolution fluorescence microscopy showed membrane association with selective regions of a tubovesicular network in the red cell. We also observed a concentration of PFGCN20 in electron-dense plaques just underneath the parasite's plasma membrane and an association of PFGCN20 with cytoplasmic vesicular structures within the parasite. The observed export of PFGCN20 and its association with the tubovesicular network in host red cells, may be indicative of the fact that PFGCN20 functions as ATP-binding subunit of an unknown multimeric ABC-transporter. The cytoplasmic localization of PFGCN20 in the parasite, however, suggests that the involvement of PFGCN20 in translational regulation or other cytoplasmic biological functions cannot be ruled out.     

Polarization of the human motor cortex through the scalp

Direct currents (DC) applied directly to central nervous system structures produce substantial and long-lasting effects in animal experiments. We tested the functional effects of very weak scalp DC (< 0.5 mA, 7 s) on the human motor cortex by assessing the changes in motor potentials evoked by transcranial magnetic brain stimulation. We performed four different experiments in 15 healthy volunteers. Our findings led to the conclusion that such weak (< 0.5 mA) anodal scalp DC, alternated with a cathodal DC, significantly depresses the excitability of the human motor cortex, providing evidence that a small electric field crosses the skull and influences the brain. A possible mechanism of action of scalp DC is the hyperpolarization of the superficial excitatory interneurones in the human motor cortex.     

Evaluation of cathepsin B levels in fresh thighs selected for cured raw ham production

Excessive meat tenderization in cured raw Parma ham has recently been correlated with abnormal levels of cathepsin B in freshly slaughtered thigh meat. We have developed a visual assay employing the substrate Z-Arg-Arg-NNapOMe for the quantitative detection of active cathepsin B levels in pork thigh muscle homogenates. The work was based on a kinetic characterization, in steady state condition, of pig muscle cathepsin B with several peptidyl chromophoric substrate analogs. This assay can easily and safely be performed by non-specialized personnel directly in the slaughterhouse or in the factory, for an early quality evaluation of thighs selected for Parma ham production. Our characterization has further indicated that the catalytic properties of porcine muscle cathepsin B and those of isoforms from other animal and plant species are practically identical. This is particularly evident in the commercially available bovine spleen isoform, which was employed as a model enzyme in most of the experiments.     

Hepatocyte growth factor exerts multiple biological functions on bovine mammary epithelial cells

The met proto-oncogene product Met is a member of the family of tyrosine kinase growth factor receptors, and hepatocyte growth factor/scatter factor (HGF/SF) has been identified as its only ligand. Bovine Met and HGF/SF have been recently cloned and their expression has been characterized in the mammary gland, but no data regarding the biological effects of this ligand/receptor couple in bovine mammary cells are yet available. We examined the role of HGF/SF and its receptor in a bovine mammary epithelial cell line (BME-UV). Expression of Met at the mRNA level in BME-UV mammary epithelial cells evaluated by real-time PCR was similar to the expression in MDCK cells, a widely used model for Met biology. Met expression in BME-UV at the protein level was confirmed by western blot. The analysis of some signal transductional pathways downstream from the Met receptor revealed that HGF/SF addition to BME-UV cells induced activation of the extracellular signal-regulated kinase ½ proliferative pathway and the Akt antiapoptotic pathway. The BME-UV cells treated with HGF responded with increased proliferation, cell scatter, and motility. Met activation by HGF induced degradation of the extracellular matrix and migration through matrigel coated transwells. Moreover, BME-UV cells included in a 3-dimensional matrix of collagen and treated with HGF developed tubular structures, reminiscent of the mammary gland ducts. These data indicate that HGF and Met might be important regulators of mammary gland growth, morphogenesis, and development in the bovine.     

Clinical impairment of sequential finger movements in Parkinson''s disease

The in vitro effects of phenylephrine solution on ciliary beat frequency (CBF) in terms of different concentrations and exposure times were investigated using a video-computerized analysis technique. Nasal epithelial cells were taken from inferior turbinate of 10 volunteers by scraping the nasal mucosa with a cytology brush. CBF was measured in five different concentrations including 0.125%, 0.25%, 0.5%, 1%, and 2.5%. Each specimen was incubated in different solution for 6 days and CBF was measured at 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 days, and 6 days. CBF decreased significantly after 12-hour incubation in 0.125% phenylephrine solution and after 8-hour incubation in 0.25% phenylephrine solution, both clinically used concentrations. There were significant decreases in CBF after incubation in 0.5% phenylephrine for 2 hours, in 1% for 1 hour, and in 2.5% for 30 minutes (P < 0.05, repeated measure analysis of variance [ANOVA]). CBF of the nasal respiratory ciliated cells significantly decreased with increasing concentrations of phenylephrine solution and with increasing incubation times at the same concentration (P < 0.05, repeated measure ANOVA). The results of this study suggest that phenylephrine may inhibit ciliary beat in vitro by its pharmacological effect at lower concentrations than clinically used ones.     

Automatic visual field: a software diagnostic procedure.

A recently developed technique for the automatic acquisition of data on visual field losses was tested, with reliable neuro-ophthalmological parameters, on 300 subjects with and without eye disorders. Algorithms for acquisition and processing of the central visual field were implemented on an IBM-AT personal computer with standard peripherals. The contours of scotomata (visual field losses) were best estimated by probabilistic adaptive enhancement of data sampling in those areas with greater visual variability. Image processing tools were specially designed to extract information concerning the size, shape, position and number of scotomata in the visual field. The diagnosis of wider campimetric lesions required parameters such as symmetry or specularity coefficients, obtainable by analysing the visual field of both eyes. Data obtained were correlated to the pathology involved by univariate statistical tools.