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P Toti

Publications and source records attributed to P Toti.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cell composition and immunohistochemical detection of VEGF, TGF-beta, and TNF-alpha in proliferative vitreoretinopathy.

Formation of vascularized membranes inside the vitreous leads to retinal detachment and blindness. In this paper it is shown that vitreal membranes are composed of newly formed vessels and myofibroblasts, immersed in a loose stroma with sparse histocytes. Vascular endothelial growth factor (VEGF) is clearly present in cellular constituents of the membranes and, therefore, represents a fundamental cytokine in their formation, while transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) are not. Considering that the composition of vitreal membranes clearly resembles scar tissue, the absence of TGF-beta in the membranes could explain their peculiar histological appearance.

Adult↗
PubMed1999

World Health Organization (WHO) and the World Heart Federation (WHF) Pathobiological Determinants of Atherosclerosis in Youth (PBDAY) Study. Histomorphometric investigation of the aorta and coronary arteries in young people from different geographical locations.

BACKGROUND AND AIM: At the Morphometric Reference Center of the World Health Organization (WHO) and the World Heart Federation (WHF) for the Pathobiological Determinants of Atherosclerosis in Youth (PBDAY) Project, histomorphometric studies were carried out on aortic and coronary artery walls of 590 people ranging from 5 to 34 yr of age, who were of European, American, Asian and African origin (6 countries) and died of trauma. The aim was to evaluate the mean intimal and medial thickness of arterial tissues. METHODS AND RESULTS: Computerized operator-assisted morphometry with a semiautomatic image analyzer was carried out on 2,893 histological slides (prepared at the WHO Reference Center in Malmö, Sweden). Our data show that age-dependent trends for prevalence of fatty streaks and atherosclerotic plaques in arteries are different: prevalence of fatty streaks increases until a plateau is reached, while exponential growth characterizes atherosclerotic plaque prevalence. Age is statistically associated with an increase in mean intimal and medial thickness in all specimens. CONCLUSIONS: Mean intimal and medial thickness differs in arterial wall specimens of individuals from various geographic locations: persons from countries with high mortality rates from cardiovascular disease tend to have greater mean intimal thickness in youth. Men with hypertension and those who smoke have significantly greater combined means of intimal thickness than normotensives and non-smokers respectively. The also have significantly greater combined means of medial thickness than normotensive men. Histomorphometric data provide evidence of the development of atherosclerotic lesions at an early age and relate their progression to ethnic and lifestyle factors and to major coronary heart disease risk factors.

Adolescent↗
PubMed1999

World Health Organization (WHO) and the World Heart Federation (WHF) Pathobiological Determinants of Atherosclerosis in Youth (PBDAY) Study. Lipid and raised lesion distribution in the right coronary artery of young people.

BACKGROUND AND AIM: As part of the WHO-WHF PBDAY Study, we examined the proximal segment of the right coronary artery (RCA) (n = 469) of 5-34 yr-old otherwise healthy trauma victims from 15 countries to establish the topographical relation of atherosclerotic lesions to age, sex and geographical location. METHODS AND RESULTS: Topography and extent of lesions were analyzed by image processing and probability-of-occurrence maps of lipid lesions (mostly fatty streaks) and raised lesions on the intimal surface of the RCA were produced. Extension of lesions varied considerably between the groups and between individuals in the same group. The prevalence of lipid lesions was 68% (319/469) compared with 100% in the aorta. The prevalence of raised lesions was 22% (102/469) compared with 7% and 26% in the thoracic and abdominal aorta. Females had more lipid lesions, whereas raised lesions prevailed in males. Lipid lesion extent increased with age in both sexes. CONCLUSIONS: High probability-of-occurrence areas for lipid and raised lesions prevailed in the proximal 5 cm of the intimal surface of the RCA (myocardial side) and were greatly overlapping. Regression analysis between lipid and raised lesion extent in the thoracic or abdominal aorta and the RCA showed no correlations between the lipid lesion extent, whereas significant correlations were found between the raised lesion extent in the RCA and the thoracic aorta only, showing that the two types of lesion behave differently in different anatomical locations.

Adolescent↗
PubMed1998

Histology of anterior capsule fibrosis following phacoemulsification.

PURPOSE: To determine the histology and immunohistochemistry of anterior capsule fibrosis. SETTING: Department of Ophthalmology and Neurosurgery and Institute of Pathology, University of Siena, Siena, Italy. METHODS: Tissue sections from 3 patients with anterior capsule fibrosis after phacoemulsification and intraocular lens implantation were examined histologically. RESULTS: The proliferating tissue was devoid of vessels and composed of dense fibrous tissue and numerous activated fibroblasts with contractile capacity (myofibroblasts). No TGF-beta, which is the most important cytokine in modulating myofibroblasts, was present in the fibrotic tissue. CONCLUSION: The absence of the cytokine TGF-beta and inflammatory cells in the proliferating tissue confirms the unique character of the reparative activity within the eye.

Aged↗
PubMed1998

Altered expression of the alpha2 laminin chain in psoriatic skin: the effect of treatment with cyclosporin.

The histopathological pattern of psoriasis is characterized by dermal inflammatory reaction and hyperproliferation of the epidermis. The mechanism of the epidermal hyperproliferation is not completely understood, but it is probably modulated by the basal lamina (BL), the alterations of which have not been described. We performed the present study to evaluate the expression of the alpha1, alpha2, beta1 and gamma1 laminin chains and collagen IV in the BL of active psoriasis vulgaris before and after cyclosporin treatment administered until the psoriasis was in remission. The results showed that the alpha2 chain is weak and irregular in the lesions, while the alpha1, beta1 and gamma1 chains and collagen IV are normal, with intense and continuous reaction. In the same subjects, this alteration was absent in skin that was clinically unaffected. After treatment with cyclosporin, the altered expression of the alpha2 chain returned to normal in the healing lesions.

Adult↗
PubMed1998

DNA ploidy pattern in choroidal melanoma: correlation with survival. A flow cytometry study on archival material.

BACKGROUND/AIMS: Paraffin embedded samples have provided an important source of material for retrospective cytofluorimetric studies, useful in establishing the predictive value of DNA content measurements. The aim of this study was to investigate the incidence and type of aneuploidy in choroidal malignant melanomas (CMM) and the significance in the clinical outcome (median follow up 55 months). METHODS: DNA content was quantified by flow cytometry in 61 CMM from archival material. Non-tumour ocular tissue was used as the reference diploid standard. Cases in which the coefficient of variation (CV) of the diploid peak was > 8% were excluded. The CMM were classified as spindle A, spindle B, mixed spindle and epithelioid, epithelioid, and necrotic. RESULTS: The frequency of the aneuploid DNA pattern was 38%. Necrotic tumours showed a worse clinical outcome independent of the ploidy pattern. Spindle A tumours were found to be diploid. Spindle B and mixed tumours showed a prevalent diploid and near diploid aneuploid pattern (DI < 1.3), yet aneuploidy was not correlated with a worse prognosis. The epithelioid tumours were prevalently diploid. However, 83% of the aneuploid tumours were hypodiploid (DI < 0.95), and showed the worst prognosis. CONCLUSION: These results indicate that increasing DNA abnormalities in CMM, especially in the epithelioid histotype, were associated with an increasing mortality.

Adult↗
PubMed1998

Inflammatory pathogenesis of cortical polymicrogyria: an autopsy study.

Polymicrogyria, a cortical abnormality usually classified among neuron migration disorders, is characterized by different etiologies and pathogeneses. Recently, it has been proposed that polymicrogyria could be acquired as a consequence of a lasting damage to the developing brain. In this study, we test the hypothesis that an infection in the fetal adnexa may give rise to distant brain defects and eventually polymicrogyria. Thirty-two fetuses spontaneously aborted for extensive ascending chorioamnionitis at 15-26 wk of gestation were evaluated. Control subjects were represented by 8 fetuses aborted at 15-24 wk of gestation. A complete autopsy was carried out between 4 and 12 h after fetal expulsion. We found different histologic alterations in the primitive cortical architecture, both isolated and combined (undulation of the cortical ribbon, untimely cortical folding/molecular layer fusion, and neuronal loss). A total of 25 cases presented one or more of the above-described morphologic alterations in the brain (78%). On the contrary, similar alterations were never observed in any of the control brains (p=0.019). Our findings indicate that chorioamnionitis significantly impairs brain cortex morphogenesis. Such neuron damage may be caused by an unspecific, indirect mechanism of injury to the developing cortex involving hypoxia and free radical generation. The reported brain abnormalities may even evolve into polymicrogyria in surviving fetuses.

Abortion, Spontaneous↗
PubMed1998

Expression of laminin 1 and 2 in brain tumor vessels. An immunohistochemical study.

Components of the blood-brain barrier (BBB) include capillary endothelial cells, the vessel basement membrane (BM) and glial cell interface. While endothelial cell peculiarities are well known and thoroughly studied, BM morphology and functional properties are not. Vessel BM throughout the body is composed of laminin 1, the most common variant of laminin, which is made up of alpha 1, beta 1, and gamma 1 laminin chains, while cerebral vessel BM has been reported to also express the alpha 2 chain. In the present study, we show that the BM of newly formed vessels in brain tumors presents the same immunohistochemical structure as normal brain vessel BM, expressing alpha 1, alpha 2, beta 1, and gamma 1 laminin chains. The function of this particular vessel structure in the central nervous system is not yet completely understood; however, we hypothesize that vessel BM could play a role in impeding the extraneural spreading of brain tumors.

Adult↗
PubMed1997

Bronchopulmonary dysplasia of the premature baby: an immunohistochemical study.

Prematurely born infants who required assisted ventilation may develop chronic lung disease or bronchopulmonary dysplasia (BPD). The cells involved in the reparative process of the premature lung are not well defined. The repair of injured tissues is a highly standardized process and the most important cells are activated (modulated) fibroblasts (myofibroblasts). A key cytokine in controlling repair is transforming growth factor-beta (TGF-beta). To characterize the cells involved in the repair process of the premature lung, we employed immunocytochemical techniques and examined the lungs of 39 autopsied premature babies who had neonatal respiratory distress syndrome (RDS). All were treated in neonatal intensive care units and required mechanical ventilation and supplemental oxygen; all survived for at least 12 hours. Antibodies were employed against vimentin, alpha-smooth muscle (alpha-SM) actin, total muscle actin, desmin, MAC387, and TGF-beta. Our study indicates that myofibroblasts are normally present along terminal airways in the developing lung. These cells increase in number some days after lung injury, form bundles of cells encircling terminal air spaces, and acquire desmin contractile filaments shortly thereafter. Myofibroblasts do not lose their contractile filaments with time, suggesting a conversion to smooth muscle metaplasia. The proliferation and migration of such myofibroblasts at sites of lung injury is associated with the presence of TGF-beta. These findings suggest that myofibroblasts play an important role in premature lung repair. They may point the way to experimental and clinical trials that will identify drugs antagonistic to TGF-beta (or other cytokines). Such antagonists may protect the neonates who are at high risk of developing BPD.

Acute Disease↗
PubMed1997

Localization of the laminin alpha 2 chain in normal human skeletal muscle and peripheral nerve: an ultrastructural immunolabeling study.

A particular form of congenital muscular dystrophy is associated with a deficiency of the tissue-specific basement membrane protein laminin alpha 2. A more precise knowledge of the normal distribution and localization of laminin alpha 2 would be useful in further elucidating the development of this disorder. In this study we used specific electron microscopic techniques, i.e., thin-section fracture labeling and cryoultramicrotomy in combination with immunogold labeling for laminin alpha 2, to determine its ultrastructural localization in normal human muscle and peripheral nerve. Both in muscle and in peripheral nerve, laminin alpha 2 is found to be associated solely with the basal lamina of myofibers and Schwann cells, respectively. Of special interest is the finding that in peripheral nerve, laminin alpha 2 is associated only with myelinated and not with unmyelinated nerve fibers.

Humans↗
PubMed1997

Localization of laminin alpha 2 chain in normal human central nervous system: an immunofluorescence and ultrastructural study.

Recently, a rare form of congenital muscular dystrophy has been shown to be associated with a deficiency of laminin alpha 2 chain, a tissue-specific component of the basal lamina. Besides muscular dystrophy, children affected with this disorder also show electrophysiological and magnetic resonance imaging evidence of white matter involvement in the central nervous system (CNS). We have studied the precise localization of laminin alpha 2 chain in normal human brain, using specific electron microscopic techniques including thin-section fracture labeling and cryoultramicrotomy, in parallel with immunohistochemical techniques. We found that this laminin chain was localized to the basal lamina of all cerebral blood vessels, whereas blood vessels of the choroid plexus did not show any reaction. No positive reaction was found in meningeal blood vessels either. We hypothesize that in normal brain, laminin alpha 2 may be important for the selective filtration capability of the blood-brain barrier. The lack of laminin alpha 2 in cerebral vessels of children with laminin alpha 2-deficient congenital muscular dystrophy may cause impaired selective filtration, leading to leakage of plasma components and damage to the CNS. Further studies should be performed on patients affected by congenital muscular dystrophy associated with laminin alpha 2 deficiency to test this hypothesis.

Adult↗
PubMed1997

Focal myositis: a polymerase chain reaction analysis for a viral etiology.

Focal myositis (FM) is a benign inflammatory condition that may clinically simulate a soft tissue sarcoma. It was first described in 1977, and only approximately 30 cases have been reported to date, yet this entity is probably more frequent. The pathogenesis of FM is totally unknown. It has been proposed that it represents a nodular form of myositis, which can evolve into polymyositis, but this hypothesis has not been confirmed by follow-up studies. We describe seven cases of FM, five of which have never been reported before. Histology of the lesions was very similar, showing a destructive inflammatory myopathy with evidence of regeneration. Our study attempted to better understand the pathogenesis of this focal inflammatory myopathy. We performed a polymerase chain reaction study to explore the presence of a number of viral infectious agents in the inflammed tissue. The present study failed to show the presence of a known viral agent with a recognized tropism for myofibers. With a panel of lymphoid cell markers, we also characterized the phenotype of the inflammatory infiltrate that was composed of many T-lymphocytes with few CD4+ cells. Lastly, we reviewed the published cases and discuss the possible pathogenesis.

Adult↗
PubMed1997

Localization of laminin chains in the human retina: possible implications for congenital muscular dystrophy associated with alpha 2-chain of laminin deficiency.

One recently described form of congenital muscular dystrophy (CMD) is associated with deficiency of the alpha 2-chain of laminin, an extracellular matrix protein that is specifically located in the basement membrane of placental villi, Schwann cells and skeletal muscle in healthy humans. This laminin is also normally present in the skin, kidney and basement membrane of blood vessels of the CNS, though it is absent from the blood vessel walls in other tissues. In this immunohistochemical study, we have explored the presence of the alpha 1, alpha 2, beta 1 and gamma 1 chains of laminin in the normal human retina, which are all localized in the basement membrane of blood vessels. This study adds to the growing evidence that the alpha 2-chain of laminin is selectively expressed in certain tissues, and suggests that CMD associated with a lack of this protein may be a multisystem disorder, with possible direct involvement of the visual system.

Adult↗
PubMed1997

Intracellular detection of laminin alpha 2 chain in skin by electron microscopy immunocytochemistry: comparison between normal and laminin alpha 2 chain deficient subjects.

The aim of this study is to localize the alpha 2 laminin chain in normal human skin. The methods used were immuno-gold cytochemistry on cryo-ultramicrotomy sections and thin-section-fracture-label, together with electron microscopy observation. Results were compared with light microscopy peroxidase immuno-staining. Both normal skin samples and skin biopsies from laminin alpha 2 chain deficient congenital muscular dystrophy affected patients were studied. The results show that, in normal skin, the laminin alpha 2 chain is spread throughout the cytoplasm of basal keratinocytes, while it appears associated with desmosomal tonofilaments in the spinous and granular epidermal layers; in skin samples from dystrophic patients the laminin alpha 2 chain was not detectable. These data suggest that the function of the laminin alpha 2 chain is different in the epidermis as compared to that in muscle and peripheral nerve, where it is localized in the basement membrane.

Humans↗
PubMed1997

Thyroid carcinoma associated with familial adenomatous polyposis.

AIMS: Thyroid carcinoma is an extracolonic manifestation that is present in about 1% to 2% of patients with familial adenomatous polyposis (FAP). Less than 100 cases have been reported in detail. We have investigated the suggestion that FAP associated thyroid carcinoma is significantly different morphologically from both papillary and follicular types and can be considered as a separate entity. METHODS AND RESULTS: Specimens from three patients with FAP associated thyroid tumours, all but one having single nodules, have been analysed. All three patients belonged to an extended kindred (23 siblings in four generations) who had genetic analysis and intensive screening for thyroid nodules. Seven patients had the same APC mutation at codon 1061. Pathological examination revealed a typical papillary carcinoma, encapsulated variant, in all patients, with follicular areas in one case. All thyroid specimens, in addition to histological and immunohistological examinations, were also specifically studied for activation of the RET-PTC oncogene, that seems to be restricted to papillary thyroid carcinoma. Two of the three patients had RET-PTC activation (PTC1 isoform). CONCLUSIONS: The findings suggest that the tumours were certainly papillary, at least in the present kindred. Further studies in different families are required for a better understanding of this peculiar tumour and of its biological behaviour.

Adenomatous Polyposis Coli↗
PubMed1997

Immunolocalization of several laminin chains in the normal human central and peripheral nervous system.

Using specific monoclonal antibodies against different subunits of laminin, we studied the differential distribution pattern of several laminin chains in the central (CNS) and peripheral (PNS) nervous system. Laminin chains alpha 1, beta 1 and gamma 1, were found in the basement membrane (BM) of blood vessels in both CNS and PNS. In contrast, laminin alpha 2 though present in the BM of capillaries in the CNS, was completely absent from PNS capillaries. Laminins alpha 2, beta 1, gamma 1 could be detected in peripheral nerve, in the BM of Schwann cells, which did not contain Laminin alpha 1. The possible importance of laminin alpha 2 for myelination in the PNS as well as in the function of the blood-brain barrier in the CNS, and its potential relevance to the pathology of congenital muscular dystrophy associated with deficiency of this laminin chain, is discussed.

Antibodies, Monoclonal↗
PubMed1996

Pulmonary pathology in surfactant-treated preterm infants with respiratory distress syndrome: an autopsy study.

The present study examines the histological features of the lungs of neonates who died of respiratory distress syndrome or related complications after surfactant therapy. Our aim was to determine whether these lungs showed any unusual histological findings. Complete autopsies were performed 6-12 h after death in 10 surfactant-treated preterm infants and in 30 infants who died before surfactant therapy was available. Representative paraffin sections of all pulmonary lobes, stained with haematoxylin and eosin, were examined microscopically. A few selected slides were also stained with periodic acid-Schiff, Vierhoff-van Gieson, and Mallory trichrome. Hyaline membrane disease and bronchopulmonary dysplasia were present in each group, although there was an increased incidence of intra-alveolar haemorrhage in surfactant-treated babies (in 8 of 10 surfactant-treated as compared with 7 of 30 untreated babies). Amongst those treated with surfactant, we observed the persistence of acute alveolar damage with unresolved hyaline membrane disease in 5 infants who died at the ages of 5, 6, 10, 12, and 13 days, respectively, and histological evidence of pneumocyte type 2 hyperplasia and dysplasia in 2 infants who died at 22 and 41 days of age, respectively. These observations reveal that surfactant-treated infants who fail to respond to therapy have continuing alveolar injury and an increased incidence of intra-alveolar haemorrhage. Since oxygen radicals can induce pneumocyte damage and necrosis and since free radicals provoke alveolar haemorrhage in animal models, we propose that the lesions we observed may stem from a lack, in some preterm babies, of specific mechanisms that detoxify oxygen radicals.

Bronchopulmonary Dysplasia↗