Neuronal Vacuolation,Myelopathy and Laryngeal Neuropathy in a Mixed‐Breed Dog

A bilateral and symmetrical neuronal vacuolation associated with spinal cord white matter degeneration and laryngeal neuropathy was observed in a 12‐week‐old male mixed‐breed dog with a history of progressive pelvic limbs ataxia. On clinical examination, signs included inspiratory stridor, spinal ataxia, tetraparesis, and proprioceptive deficits more severe in the pelvic limbs. Examination of the larynx showed bilateral laryngeal paralysis and electromyography revealed fibrillation potentials restricted to the intrinsic laryngeal muscles. Clinical and pathological findings resembled the syndrome of neuronal vacuolation and spinocerebellar degeneration described in Rottweiler dogs. This is the first report of a similar disorder in a dog different from Rottweiler.     

Managing uncertainty in diagnosis of acute coronaric ischemia

The paper presents the reasoning mechanism of COR, a knowledge-based system (KBS) able to provide support for the diagnosis of coronaric ischemia by integrating the interpretation of chest pain, 12-lead ECG, and bio-marker concentrations. Chest pain features are collected interactively through a questionnaire. The ECG signal is acquired in SCP format. Any set of bio-markers can be considered. Data input is incremental and possibly incomplete. Reasoning is based on revised uncertainty calculus, which allows a formal treatment of verbally expressed uncertainty concerning both input data and diagnostic rules. Each diagnosis is supplemented by a linguistic label, expressing the plausibility of the disease identified, given the symptoms observed.     

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.     

Inducible nitric oxide synthase expression in human colorectal cancer: correlation with tumor angiogenesis

To investigate the potential involvement of the nitric oxide (NO) pathway in colorectal carcinogenesis, we correlated the expression and the activity of inducible nitric oxide synthase (iNOS) with the degree of tumor angiogenesis in human colorectal cancer. Tumor samples and adjacent normal mucosa were obtained from 46 surgical specimens. Immunohistochemical expression of iNOS, vascular endothelial growth factor (VEGF), and CD31 was analyzed on paraffin-embedded tissue sections. iNOS activity and cyclic GMP levels were assessed by specific biochemical assays. iNOS protein expression was determined by Western blot analysis. iNOS and VEGF mRNA levels were evaluated using Northern blot analysis. Both iNOS and VEGF expressions correlated significantly with intratumor microvessel density (r(s) = 0.31, P = 0.02 and r(s) = 0.67, P < 0.0001, respectively). A significant correlation was also found between iNOS and VEGF expression (P = 0.001). iNOS activity and cyclic GMP production were significantly higher in the cancer specimens than in the normal mucosa (P < 0.0001 and P < 0.0001, respectively), as well as in metastatic tumors than in nonmetastatic ones (P = 0.002 and P = 0.04, respectively). Western and Northern blot analyses confirmed the up-regulation of the iNOS protein and gene in the tumor specimens as compared with normal mucosa. NO seems to play a role in colorectal cancer growth by promoting tumor angiogenesis.     

Expression and cell distribution of the intercellular adhesion molecule, vascular cell adhesion molecule, endothelial leukocyte adhesion molecule, and endothelial cell adhesion molecule (CD31) in reactive human lymph nodes and in Hodgkin''s disease.

The immunocytochemical expression of intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), endothelial leukocyte adhesion molecule (ELAM-1), endothelial cell adhesion molecule (EndoCAM CD31), and HLA-DR antigens was investigated in sections of 24 reactive lymph nodes and in 15 cases of Hodgkin's disease. ICAM-1 was detected in sinus macrophages, follicular dendritic reticulum cells (FDRCs), interdigitating reticulum cells (IDRCs), epithelioid macrophages, Hodgkin's cells (HCs), and vascular endothelium. ICAM-1 expression was often associated with that of HLA-DR antigens. VCAM-1 was detected in FDRCs, in fibroblast reticulum cells (FRCs), in macrophages, and in rare blood vessels. EndoCAM (CD31) was constitutively expressed in all types of endothelial cells, sinus macrophages, and in epithelioid granulomas. ELAM-1 was selectively expressed by activated endothelial cells of high endothelium venules (HEVs). When expression of the inducible adhesion molecules ICAM-1, VCAM-1 and ELAM-1 was comparatively evaluated in HEVs, it was found that ICAM-1 + HEVs were present in all reactive and HD nodes, whereas ELAM-1 and/or VCAM-1 were expressed only in those pathologic conditions characterized by high levels of interleukin-1/tumor necrosis factor (IL-1/TNF) production, such as granulomatosis and Hodgkin's disease. In Hodgkin's disease, the expression of ELAM-1/VCAM-1 was more pronounced in cases of nodular sclerosis and was associated with a significantly higher content of perivascular neutrophils.     

Characterization of EN4 monoclonal antibody: a reagent with CD31 specificity.

EN4 MoAb was originally described as a MoAb that reacts specifically with human endothelial cells, and the reagent was not assigned to any of the presently known CD. Here, we provide evidence indicating that EN4 reacts with the CD31 antigen. Thus, EN4 stains strongly murine fibroblasts transfected with the human CD31 gene. Furthermore, SDS-PAGE analysis of immunoprecipitates of cell lysates from surface-iodinated Jurkart T cells demonstrated that EN4 and reference CD31 MoAb recognized the same antigen, of 130 kD mol. wt. Finally, both EN4 and CD31 gave the same pattern of reactivity when tested on tonsillar or peripheral blood lymphoid cells by FACS analysis or by immunohistochemistry on sections of a variety of human tissues. EN4, however, proved consistently more efficient than the reference anti-CD31 MoAb as judged by both the intensity of fluorescence or of tissue staining. This property has thus allowed a better characterization of the tissue and cellular distribution of CD31.