Giuseppe Santeusanio

Aging and atherosclerosis in the rabbit: 1. Distribution, prevalence and morphology of atherosclerotic lesions

Aging is considered a risk factor in the pathogenesis of atherosclerosis. It is not clear, however, whether the relationship between aging and atherosclerosis is the result of increased susceptibility of the arterial wall related to intrinsic alterations or the expression of the increase in intensity or duration of exposure to risk factors. In this study, we used aged (median age 46 months) and young (4 months old) New Zealand white rabbits. Nine aged and 11 young rabbits received a hyperlipemic diet enriched with a low dose of cholesterol for 18 months. Eleven aged and 8 young rabbits, fed standard chow for the same period, were used as controls. Using morphologic and morphometric methods, we detected in aged hyperlipemic rabbits (a) a marked prevalence of fibroatheromatous plaques (as opposed to fatty streaks in young hyperlipemic rabbits); (b) aortic lesions more extensive and of greater dimensions than in young hyperlipemic rabbits; (c) fibroatheromatous plaques in carotids and raised fatty streaks in the large subepicardial coronary branches. Our results show an increased susceptibility of the aged arterial wall to hypercholesterolemia.

Foam cells of the rabbit atherosclerotic plaque arrested in metaphase by colchicine show a macrophage phenotype

Proliferative activity of smooth muscle cells and foam cells characterizes experimental atherosclerotic plaques as they first appear. Immunohistochemical and ultrastructural methods were applied to cells arrested in metaphase by colchicine and the phenotype of cells in mitosis was detected. Most of the metaphase arrested FC found in aortic plaques of cholesterol fed New Zealand rabbits were positive to the anti-macrophage monoclonal antibody and negative to the anti-smooth muscle actin monoclonal antibody. Moreover, most of the metaphase blocked FC had the ultrastructural features of macrophages. These preliminary results further strengthen previous observations on rabbit plaques that the FC pool is mainly constituted by macrophages and show, for the first time, that the dimension of this pool depends not only on migration of circulating monocytes but also on the in situ proliferation of macrophages.

Relationships between risk factors and morphological patterns of human carotid atherosclerotic plaques. A multivariate discriminant analysis

The histological characterization of the fibroatheromatous plaques and their histogenesis are still to be defined. Factors responsible for the evolution of intimal components and the mechanisms and stages of fibroatheromatous plaque formation are still largely obscure. Focusing on symptomatic plaques, the aim of this study is to determine whether plaque heterogeneity is the result of a haphazard clustering of various components or an organized pattern in response to risk factors. To this end, 180 carotid plaques from patients affected by transient ischemic attacks (TIA) or by stroke, with angiographic stenosis greater than 50%, were studied after endoarterectomy. Clinical and morphological data were collected by means of a pre-defined protocol, quantified and correlated, by using the discriminant analysis, with age, sex, hypertension, diabetes, hypercholesterolemia and smoking habit. Our results show that the relationships between plaque components are non-random and consistent with the knowledge derived from studies on human and experimental plaques. Moreover, some plaque patterns can be significantly correlated with single risk factors. The fibrous plaque was correlated with aging and diabetes; the granulomatous plaque, rich in giant cells, with the female sex and hypertension; the xanthomatous plaque, rich in foam cells and with extensive alcianophilia, with hypercholesterolemia. In the smokers, finally, the plaques were frequently complicated by mural thrombosis.

Thyroid fine needle aspiration cytology processed by ThinPrep: an additional slide decreased the number of inadequate results.

E. D. Rossi, F. Morassi, G. Santeusanio, G. F. Zannoni and G. Fadda 
Thyroid fine needle aspiration cytology processed by ThinPrep: an additional slide decreased the number of inadequate results

Histological, Immunohistochemical, and Ultrastructural Findings in Human Corneas After Photorefractive Keratectomy

BACKGROUND Four human corneas that had undergone photorefractive keratectomy (PRK) and subsequent penetrating keratoplasty were examined by means of light and electron microscopy in an attempt to detect possible causes for complications after PRK. METHODS Four eyes with a central corneal leukoma resulting from a previous PRK treatment underwent penetrating keratoplasty respectively 3 days, 3 months, 5 months, and 13 months after the refractive procedure. Different excimer laser instruments (Meditec MEL 50, Summit UV200, and VISX 20/20) had been used. The corneal buttons removed were submitted for light microscopy, electron microscopy and immunohistochemistry. RESULTS An immature (one to two layers, basement membrane anomalies) but continuous epithelium was present even in the 3-day specimen; between six and eight epithelial layers could be seen in the 13-month specimen, which still presented an undulated aspect of the otherwise normal basement membrane. A continuous acellular collagen layer underlying the epithelium of the ablated area was detected in the superficial stroma of all examined corneas. No Descemets membrane or endothelial alterations could be seen. CONCLUSIONS Despite recovery of a continuous epithelial layer as early as 3 days after PRK, abnormalities of both epithelium and superficial stroma could be detected in all specimens, including the one obtained 13 months after the refractive procedure.

Cytokeratin profiles of male breast cancers

Aims:  The prognostic factors and expression of molecular markers in male breast carcinomas are similar to those in female breast cancers. The identification of distinct cytokeratin (CK) profiles (basal as opposed to luminal cells) helps to identify subsets of tumours with different clinical behaviour. The aim of this study was to investigate CK expression in male breast cancer.

Diagnostic and prognostic role of HBME-1, galectin-3, and β-catenin in poorly differentiated and anaplastic thyroid carcinomas.

Aim:Thyroid cancer represents the first endocrine malignant neoplasm, accounting for 1% of human malignancy. The majority of which are well-differentiated cancer representing up to 90% of thyroid cancer and pursuing a favorable clinical course. The groups of poorly differentiated thyroid cancer (PDC) and anaplastic thyroid cancer (ATC) have a poor outcome and need a strict clinical surveillance. Materials and Methods:Thirty-four cases including 23 PDC/insular cancer and 9 ATC were examined for the expression of an immunohistochemical panel made up by HBME-1, galectin-3, and &bgr;-catenin and correlated either with histologic prognostic parameters or the overall surveillance. Results:HBME-1 and galectin-3 were expressed in 100% of the PDC/insular cases and in none of the ATC cases. The data for &bgr;-catenin pointed out an 80% expression (12/15) in the PDCs and only a focal and nonspecific positivity in the ATCs. A &bgr;-catenin-positive expression was found in all patients with a worse outcome/death and in the presence of vascular invasion and metastatic disease. All 3 PDC patients with &bgr;-catenin negativity are alive, whereas only 41% (5/12) are alive in the &bgr;-catenin-positive group. Conclusions:Our data set up the idea that PDC represents an intermediate step in the biological process of dedifferentiation of thyroid tumors toward ATC. This shift is underlined by the &bgr;-catenin expression, which seems to be related to a worse prognostic behavior. HBME-1 and galectin-3 show a similar pattern in PDC compared with well-differentiated carcinoma, whereas they are not expressed, as well as &bgr;-catenin, in anaplastic carcinomas.

Carcinoma of the vulva with sarcomatoid features: a case report with immunohistochemical study.

A tumor of the vulva with sarcomatoid features was studied by immunocytochemistry to characterize the phenotype of the spindle-shaped and giant cells. Sarcomatoid-looking cells were positive for intermediate filament keratin polypeptides of stratified epithelium. These results favor histogenesis of the sarcomatoid-looking cells from a metaplastic alteration of the malignant squamous component.

Immunohistologic detection of estrogen receptors in paraffin-embedded breast cancers: Correlation with cytosol measurements

Paraffin-embedded sections of 76 human breast tissue specimens were analyzed for estrogen receptors (ER) and endogenous bound estrogen (ER-E). Preincubation of sections with polyestradiol phosphate was followed by stabilization of the complex with glutaraldehyde. The bound hormone was then visualized by the peroxidase-antiperoxidase (PAP) technique with antiestradiol as the primary antiserum. Normal breast tissue and benign proliferations were consistently positive for ER and ER-E. All specimens were examined for free and bound receptors in cytoplasm and nuclei. Among the carcinomas examined, a high correlation was found between the presence of ER by the PAP method and by the biochemical analysis of cytosol preparations. The PAP method, requiring no special preparation of surgical specimens, overcomes many of the disadvantages of the cytosol method and adds the advantage of independent evaluation of nuclear and cytoplasmic estrogen binding sites.

The Genetics of Signal Transduction and the Feto-Maternal Relationship. A Study of Cytosolic Low Molecular Weight Phosphotyrosine Phosphatase

Intracellular kinases mediate positive signalling from surface receptors by phosphorylating critical target proteins whereas phosphatases inhibit this process. Differential phosphatase activity at the feto-maternal interface could determine the appropriate relative growth and development on each side of the placenta. The highly polymorphic cytosolic low molecular weight phosphotyrosine-phosphatase (ACP1-cLMWPTPase) has been studied in 170 women who had at least two consecutive spontaneous abortions along with their husbands and in 352 normal puerperae along with their newborn babies. Symmetry analysis of joint wife/husband and mother/infant distribution suggests that when ACP1 activity is lower in the mother than in either her aborted fetus or her child, the probability of abortion is higher and the survival to term is lower as compared to pairs in which the ACP1 activity is higher in the mother than in her fetus. Further analysis has shown that the effect is due to S isoform: i.e. a high mother/fetus S isoform ratio favours intrauterine survival. Analysis of gestational duration and birth weight suggests that a high ACP1 maternal activity coupled with a low or moderate fetal activity favour fetal growth and developmental maturation. The present data indicate that maternal-fetal genetic differences in signal transduction could contribute significantly to variability of intrauterine developmental parameters and to pathological manifestation of pregnancy.