Maria Morini

Lectins and superantigens: Membrane interactions of these compounds with T lymphocytes affect immune responses

1. Lectins and superantigens belong to two different families of macromolecules which are able to interact with cells of the immune system. 2. The principal mechanisms by which they modulate immune responses are presented in this review. 3. Possible similarities shared by these proteins and their common mechanisms of action upon immunocytes will be presented along with a brief discussion regarding the role of these molecules in physiological immune responses and human diseases.

Acute Phase Reactant α1antichymotrypsin Is Increased in Cerebrospinal Fluid and Serum of Patients with Probable Alzheimer Disease

Levels of α1-antichymotrypsin (α1-ACT) in cerebrospinal fluid (CSF) and serum from patients with probable Alzheimer disease (AD) of both early (e-AD) and late (1-AD) onset assessed by a competitive enzyme-linked immunosorbent assay were higher than those found in controls or in patients with vascular dementia (VD). A negative correlation between CSF levels of α1-ACT and the stage of the disease was present in patients with both e-AD and 1-AD. No difference in α1-macroglobulin levels in CSF and serum from patients with e-AD, 1-AD, VD, and nondemented controls was found. Serum concentrations of α1-antitrypsin from 1-AD subjects were within the normal range. Thus, increased levels of α1-ACT in CSF and serum were specifically associated with AD, and the detection of this serpin in CSF may be useful in monitoring the progression of the disease.

C-kit Gene Product (CD117) Immunoreactivity in Canine and Feline Paraffin Sections

CD117 is a transmembrane tyrosine kinase growth factor receptor expressed by a variety of normal human cell types, including germ cells, immature myeloid cells, and mast cells. To evaluate the pattern of CD117 expression in dogs and cats, we applied a polyclonal antibody on paraffin sections from 44 samples of normal tissues and 104 tumors. In both species, strong immunoreactivity was observed in mast cells, interstitial cells of Cajal, and in mast cell tumors. Among gastrointestinal mesenchymal neoplasms, tissues from five dogs and one cat revealed strong CD117 expression, enabling us to identify them as gastrointestinal stromal tumors (GISTs).

Mitogenic activity and immunological properties of bolesatine, a lectin isolated from the mushroom Boletus satanas Lenz

1. A lectin has been purified from the mushroom Boletus satanas Lenz. 2. The protein, called bolesatine, is mitogenic for human T lymphocytes in a dose- and time-dependent manner. 3. Optimal mitogenic doses induce the release of interleukin-1 alpha and interleukin-2 from mononuclear cell cultures.

Gastrointestinal spindle cell tumours of the dog: histological and immunohistochemical study.

To assess the relevance of spindle cell tumours in the canine gastrointestinal (GI) tract and to classify them, a retrospective study was carried out on haematoxylin and eosin-stained sections from formalin-fixed paraffin wax-embedded samples of 105 primary GI tumours. Seventeen out of 105 (16%) GI tumours were mesenchymal, 48% were epithelial and 36% were round cell tumours. Spindle cell tumours were stained by Masson trichrome, Orcein-Van Gieson and labelled immunohistochemically (vimentin, desmin, smooth muscle actin, protein S100, glial fibrillar acid protein, CD117 and MIB-1) and the histological grade, mitotic index, nuclear size and cellular density were also assessed. The 17 gastrointestinal mesenchymal tumours were classified as 10 leiomyomas (10/10 positive for desmin and smooth muscle actin; 6/10 positive for vimentin) 2 leiomyosarcomas (2/2 positive for desmin, smooth muscle actin and vimentin) and 5 gastrointestinal stromal tumours (GISTs) (5/5 positive for CD117 and vimentin; 3/5 positive for smooth muscle actin). Canine GISTs appeared as densely packed spindle cell tumours, with a diffuse, strong, cytoplasmic immunopositivity for c-kit protein (CD117). GISTs, defined as CD117-positive spindle cell or epithelioid or pleomorphic neoplasms that presumably derive from interstitial cells of Cajal, are reported in recent medical studies as the most common mesenchymal tumours of the GI tract. Our data suggest that GISTs represent a significant portion of canine GI spindle cell tumours, which can be definitely distinguished from leiomyosarcomas only by their expression of CD117.

Expression of the KIT protein (CD117) in primary cutaneous mast cell tumors of the dog

Thirty-one canine cutaneous masses, diagnosed as mast cell tumors (MCT) by histopathologic analysis, were used to evaluate the immunohistochemical pattern of expression of KIT protein (CD117), a type III tyrosine kinase protein involved in mast cell growth and differentiation. Lesions were graded as I (well differentiated), II (intermediate differentiation), or III (poorly differentiated) according to the following morphologic features: invasiveness, cellularity and cellular morphology, mitotic index, and stromal reaction. Immunohistochemical KIT expression was compared with histologic grade and some histomorphologic features (cell differentiation and nuclear grade) evaluated separately. A possible predictive role of biologic behavior in MCTs for KIT expression was also investigated. Immunohistochemical analysis revealed three different patterns of KIT expression: a cytoplasmic diffuse pattern, a membranous pattern with immunostaining located on the cell surface, and a cytoplasmic perinuclear pattern, where KIT expression was detected in the cytoplasm of the neoplastic mast cells, close to the nucleus. Statistical analysis showed a close relationship between different KIT immunohistochemical patterns and histologic grade (P < 0.00000), cell differentiation (P < 0.00000), and nuclear grade (P < 0.0024). According to Kaplan-Meier–estimated survival curves compared by survival analysis, KIT expression was significantly associated with survival time (P = 0.037) but not cancer-free interval (P = 0.50). Similar to other well-known histomorphological features, KIT expression is a useful parameter of malignancy in cutaneous MCTs. KIT expression also predicted the biological behavior of the tumors in this study.

Cell Adhesion Molecules CD11a and CD18 in Blood Monocytes in Old Age and the Consequences for Immunological Dysfunction

Adhesion molecules, such as leukocyte-function-associated antigen (LFA-1 or CD11a/CD18), intercellular adhesion molecule 1 (ICAM-1 or CD54) and Hermes antigen (HCAM or CD44), have important roles in many adhesive interactions involving cells of the immune system. Since it has been shown that many immunological alterations were present in aged subjects, we studied the expression and density of these molecules on peripheral blood lymphocytes and monocytes from healthy old subjects. A decrease in monocyte subpopulations bearing CD11a/CD18 and an increase in CD11a/CD18 and and CD44 antigen density on lymphocytes and on monocytes, respectively, were observed. These changes might be an event in the mechanism leading to the decreased lymphocyte proliferative response in vitro and to other immunological dysfunctions reported in old subjects.

Epidermal growth factor receptor expression is predictive of poor prognosis in feline cutaneous squamous cell carcinoma

The aim of this study was to investigate epidermal growth factor receptor (EGFR) expression in feline cutaneous squamous cell carcinoma (FC-SCC) and assess its prognostic role. Nineteen formalin-fixed paraffin-embedded excisional biopsies of FC-SCC were tested for EGFR expression using immunohistochemistry (IHC). Relationships between EGFR expression and histopathological parameters (differentiation, mitotic activity), disease-free interval (DFI) and overall survival (OS) at 24 months were further investigated. Fourteen of 19 tumours (73.7%) were positive for EGFR, with great variation in intensity and proportion of labelled cells. EGFR expression was not correlated with tumour differentiation or mitotic activity. Nine cats (47.4%) died of tumour-related causes. Patients with EGFR-positive tumours had a significantly worse outcome (P=0.0217), with decreased DFIs (P=0.0075) and survival times (P=0.0391). These data suggest that EGFR expression carries a negative prognostic significance in FC-SCC. EGFR inhibitors in association with conventional treatments may improve outcome for the subgroup of cats with EGFR-positive tumours.

Hypertrophy of intestinal smooth muscle in cats

Pathological findings of four cats with severe and diffuse smooth muscle hypertrophy of the small intestine (MHSI) are reported and compared to those of five cats with segmental MHSI secondary to neoplastic obstruction and four controls. Histology demonstrated a constant association between idiopathic MHSI and submucosal fibrosis and chronic lymphoplasmacytic enteritis. Morphometry (gut diameter, thickness and area of muscular layers, number and density of smooth muscle nuclei) and MIB-1-immunolabelling showed that the thickness increase was mostly due to hypertrophy, but hyperplasia was also evident. Microbiology from ileal content samples was performed in two cats with primary MHSI, and Campylobacter spp. were isolated, which were also demonstrated by immunohistochemistry and ultrastructure. The association of chronic enteritis with idiopathic MHSI suggests that factors released in intestinal inflammation may also act as hypertrophy stimuli for smooth muscle cells.

Purification and partial characterization of a mitogenic lectin from the latex of Euphorbia marginata

A lectin was purified from the latex of Euphorbia marginata by affinity chromatography on acid-treated Sepharose 6B and elution with lactose. The lectin is a glycoprotein composed of two identical subunits with M(r) 30,000, approx. The haemagglutinating activity of the lectin is not specific for any human blood group, and is inhibited by galactose and galactose-containing sugars and by gentiobiose. The lectin is strongly mitogenic for human T-lymphocytes and induces the release of interleukin-1 beta and tumor necrosis factor-alpha from cultured mononuclear cells.