Object recognition by artificial cortical maps.

Object recognition is one of the most important functions of the human visual system, yet one of the least understood, this despite the fact that vision is certainly the most studied function of the brain. We understand relatively well how several processes in the cortical visual areas that support recognition capabilities take place, such as orientation discrimination and color constancy. This paper proposes a model of the development of object recognition capability, based on two main theoretical principles. The first is that recognition does not imply any sort of geometrical reconstruction, it is instead fully driven by the two dimensional view captured by the retina. The second assumption is that all the processing functions involved in recognition are not genetically determined or hardwired in neural circuits, but are the result of interactions between epigenetic influences and basic neural plasticity mechanisms. The model is organized in modules roughly related to the main visual biological areas, and is implemented mainly using the LISSOM architecture, a recent neural self-organizing map model that simulates the effects of intercortical lateral connections. This paper shows how recognition capabilities, similar to those found in brain ventral visual areas, can develop spontaneously by exposure to natural images in an artificial cortical model.     

Topical application of isosorbide dinitrate in patients with persistent constipation after pull-through surgery for Hirschsprung's disease.

AIMS: The aim of this study was to evaluate the anal manometric changes and the clinical effects after topical application of isosorbide dinitrate (ISDN) in patients with persistent constipation after pull-through surgery for Hirschsprung's disease (HD). METHODS: We studied 3 children (2 males and 1 female), aged 2, 3 and 5 years respectively, who had undergone the Soave-Boley surgical procedure for HD and who suffered from persistent constipation after operation. We performed a pre- and postoperative anorectal manometry study and we applied ISDN paste (1 mg/kg two times daily) in the anal region for three weeks. All patients were followed-up and re-evaluated at 1, 3, and 6 months. RESULTS: All patients showed an improvement of symptoms, with an average of 4 spontaneous evacuations per week. Prior to the topical treatment, the medium pressure was 115.6 mmHg (range 102 - 130 mmHg), the maximum pressure was 160 mmHg (range 145 - 175 mmHg), and the medium length of the high pressure zone was 1.8 cm (range 1.5 - 2.0 cm). At the 6 month follow-up, the medium pressure was 57.3 mmHg (range 52 - 61 mmHg, a decrease of 54.4 %), the maximum pressure was 98 mmHg (range 88 - 107 mmHg; a decrease of 38.7 %), and the medium length of the high pressure zone was 1.6 cm (range 1.4 - 1.8 cm; a decrease of 11.1 %). CONCLUSIONS: Topical treatment with ISDN is a valid therapeutic alternative to an anal myotomy in patients with persistent constipation after pull-through surgery for HD. However, a greater number of cases and a longer follow-up are necessary to confirm the validity of our experience.     

HER-2/neu and bcl-2 in ovarian carcinoma: clinicopathologic, immunohistochemical, and molecular study in patients with shorter and longer survival.

The bcl-2 protein is a membrane protein involved in prolonging cell survival by inhibiting apoptosis. The HER-2 oncogene, which is located on chromosome 17 and encodes for a tyrosine-kinase growth factor receptor, is amplified and HER-2/neu is overexpressed in 25% to 30% of breast carcinomas. The authors analyzed the bcl-2 expression and the bcl-2 gene and HER-2/neu overexpression and amplification in FIGO stage IIIC, serous, G3, ovarian carcinomas obtained from living patients who had no evident disease 5 years after primary treatment compared with ovarian carcinomas obtained from patients, matched for stage, grade of differentiation, and treatment, who had died of progression of disease no later than 2 years after primary treatment. bcl-2 overexpression was statistically correlated with progression of disease during first-line chemotherapy (P=0.021). The HER-2/neu status was found not to correlate with progression of disease during first-line chemotherapy. Both bcl-2 and HER-2/neu expression were not statistically associated with the clinical outcome of ovarian cancer patients. Gene amplification of the HER-2/neu chromosome 17 was found in all the HER-2/neu, 3+ score, positive-staining ovarian carcinomas. None of the analyzed samples revealed a translocation t(14;18)(q32;q21) in the bcl-2 gene. The knowledge of additional prognostic or even predictive factors, such as bcl-2 expression, in patients with advanced ovarian carcinoma before the primary chemotherapeutic treatment may help in the management of patients who require a more tailored treatment. In addition, the gene amplification of the HER-2/neu suggests that HER-2 is a potential target for treatment in ovarian cancer.     

Correlation of epidermal growth factor receptor expression with tumor microdensity vessels and with vascular endothelial growth factor expression in ovarian carcinoma

We analyzed in advanced ovarian serous G3 carcinoma the correlation between epidermal growth factor receptor (EGFR) overexpression and tumor angiogenesis and their relation with clinical outcome. Microvessel density (MVD) and vascular endothelial growth factor (VEGF) were statistically correlated with disease-free interval and death from disease both in univariate and multivariate analyses while EGFR expression was not correlated with clinical outcome. MVD was significantly associated with progression of disease during chemotherapy while VEGF and EGFR expression were not correlated with responsiveness to chemotherapy (Fisher's exact test). VEGF expression was correlated with MVD (Fisher's exact test). EGFR showed a trend to correlation with MVD. Further studies focusing on the use of angiogenesis inhibitors in addition to EGFR inhibitors on ovarian carcinoma cells may produce therapeutic strategies in the selection of tailored therapies in ovarian cancer patients.     

Serum Interferon (IFN)-Neutralizing Antibodies and Bioactivities of IFNs in Patients with Severe Type II Essential Mixed Cryoglobulinemia

The efficacy of alpha interferon (IFN-α) in the treatment of severe type II essential mixed cryoglobulinemia (EMC) has been reported previously. In some patients, the development of neutralizing antibodies to recombinant IFN-α (rIFN-α) can affect the clinical response achieved with rIFN-α; a second treatment with natural IFN-α preparations may reinduce the clinical response. In the present study the ability of leukocyte IFN (LeIFN) to restore the response was investigated from a pharmacodynamic viewpoint. Specifically, the pharmacodynamic profiles of different IFN-α preparations were studied by measuring the serum neopterin levels and the levels of expression of protein MxA mRNA in in vivo peripheral blood mononuclear cells in two patients with EMC whose resistance to rIFN-α2a treatment increased concomitantly with the development of neutralizing antibodies. These markers were measured before injection and at 24 and 48 h after a single injection of rIFN-α2a, consensus IFN [(C)IFN], or LeIFN. No increase or only a slight increase in MxA mRNA levels was detectable after administration of rIFN-α2a or (C)IFN, whereas a significant increase (≥10-fold) in MxA mRNA expression was recorded following administration of LeIFN. The neutralizing antibodies to rIFN-α2a cross-react with (C)IFN. Sera from these patients neutralized most but not all of the subtypes present in the natural IFN-α (LeIFN) mixture, and no significant increase in neopterin levels was observed after these patients were switched to LeIFN treatment. In summary, the data demonstrate that the problem of neutralizing antibodies still exists and that LeIFN may induce an increase in the level of MxA mRNA expression but not an increase in neopterin levels in patients who are resistant to treatment with rIFN-α2a or (C)IFN.     

Antigenic and immunogenic mimicry of the HER2/neu oncoprotein by phage-displayed peptides

To recover peptides that antigenically and immunogenically mimic the p185^HER2 oncoprotein, we selected the phage-peptide libraries pVIII-9aa and pVIII-9aa. Cys using murine monoclonal antibodies (mAb) MGr2 and MGr6, directed against two distinct epitopes of the p185^HER2 extracellular domain. Phagedisplayed peptides containing consensus amino acid motifs were recovered and shown to compete specifically for mAb binding on tumor cells that overexpress p185^HER2. The deduced amino acid sequence of the peptides suggests that both epitopes defined by the mAb on p185^HER2 are discontinuous and that hydrophobic interactions are involved in binding with the mAb. A phage clone displaying the GPLDSLFAQ peptide elicited a specific immune response against the p185^HER2 in BALB/c mice, demonstrating that this phage-displayed peptide represents an immunological equivalent of the MGr2 epitope on p185^HER2 and might be used as a substitute for this oncoprotein in in vitro and in vivo immunological studies.     

Neutralizing and binding antibodies to IFN-beta: relative frequency in relapsing-remitting multiple sclerosis patients treated with different IFN-beta preparations.

The frequencies of anti-interferon-beta (IFN-beta) antibody development reported to date in patients treated with different IFN-beta preparations are not readily comparable mainly because of differences in underlying diseases and assay methods. Thus, the frequency of neutralizing antibody (NAb) and binding antibody (BAb) development was analyzed in a sample of sera derived from a homogeneous group of relapsing-remitting multiple sclerosis (RRMS) patients treated with different IFN-beta preparations. The frequency of developing NAb and BAb to IFN-beta varied according to the IFN-beta given. Specifically, the NAb seroconversion frequency was significantly higher in patients treated with Betaferon, Schering AG, Berlin, Germany (31.3%) than in patients treated with both preparations of recombinant IFN-beta 1a (Rebif, Serono, Geneva, Switzerland [7.4%] or Avonex, Biogen, Cambridge, MA [6.3%]). Analysis of BAb seroconversion frequency in the same patients revealed that different IFN-beta preparations may also have different capability to induce BAb development and that BAb are produced during IFN-beta therapy at a significantly higher rate than NAb. Our main conclusion is that different human IFN-beta preparations may possess different immunogenicities, leading to varying frequency of development of antibody to IFN-beta in RRMS.     

Haemophilus influenzae porin induces Toll-like receptor 2-mediated cytokine production in human monocytes and mouse macrophages

The production of proinflammatory cytokines is likely to play a major pathophysiological role in meningitis and other infections caused by Haemophilus influenzae type b (Hib). Previous studies have shown that Hib porin contributes to signaling of the inflammatory cascade. We examined here the role of Toll-like receptors (TLRs) and the TLR-associated adaptor protein MyD88 in Hib porin-induced production of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Hib porin-induced TNF-alpha and IL-6 production was virtually eliminated in macrophages from TLR2- or MyD88-deficient mice. In contrast, macrophages from lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ mice, which are defective in TLR4 function, responded normally to Hib porin. Moreover anti-TLR2 antibodies but not anti-TLR4 antibodies significantly reduced Hib porin-stimulated TNF-alpha and IL-6 release from the human monocytic cell line THP-1. These data indicate that the TLR2/MyD88 pathway plays an essential role in Hib porin-mediated cytokine production. These findings may be useful in the development of alternative therapies aimed at reducing excessive inflammatory responses during Hib infections.     

X-linked recessive chondrodysplasia punctata: spectrum of arylsulfatase E gene mutations and expanded clinical variability

Partial trisomy of the long arm of chromosome 10 is a well-defined but rare syndrome. Clinical features of this chromosomopathy are a distinctive dysmorphic appearance, developmental delay, growth retardation, and in some cases, abnormalities of the extremities and renal, cardiac and ocular anomalies. This report describes a neonate with symmetric growth retardation and multiple dysmorphic features, in whom chromosomal analysis revealed a partial trisomy of chromosome 10q with a monosomy of the 13q34 region. The phenotype shares many common features with previously published cases. In addition to the typical features, our case also shows renal hypoplasia with early renal insufficiency and some genital anomalies.