Biomedical subjects

L G Spagnoli

Publications and source records attributed to L G Spagnoli.

At least 19 recordsLinked to original sources

PubMed1995

Propionyl-L-carnitine prevents the progression of atherosclerotic lesions in aged hyperlipemic rabbits.

We have characterized the extent and the phenotype of total and proliferating cell population of aortic plaques in aged rabbits receiving a long-term low-dose cholesterol hyperlipemic diet, which represents an experimental model of atherosclerosis. For nine months, rabbits received the hypercholesterolemic diet alone or in addition to a treatment with propionyl-L-carnitine (PLC), a derivative of carnitine, an intramitochondrial carrier of fatty acids present in most cell types. We observed that, in both PLC-treated and control hyperlipemic rabbits, the ratio between proliferating macrophage-derived and smooth muscle cells was 2:1. PLC in addition to the hypercholesterolemic diet induced a marked lowering of plasma triglycerides, very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) triglycerides, while plasma cholesterol was slightly and transiently reduced. Moreover, PLC-treated hyperlipemic rabbits exhibited a reduction of plaque thickness and extent, a slight but significant reduction of the percentage of macrophage-derived cells as compared to control hyperlipemic animals and a reduction of the number of both proliferating macrophage- and smooth muscle cell-derived foam cells. Finally, both proliferating and non-proliferating plaque cells expressed large amounts of macrophage colony-stimulating factor protein, in particular macrophage-derived foam cells. These results indicate that a modification of plasma lipemic pattern obtained by a long-term oral administration of PLC was associated with a decrease of plaque cell proliferation and severity of aortic atherosclerotic lesions.

Aging↗

PubMed1995

Intramuscular myxoma of the face: an unusual localization. A clinicopathological study.

BACKGROUND: Intramuscular myxoma is a rare benign mesenchymal lesion. Only very rare cases of cutaneous localization of this tumor have been described, in particular related to the somatic soft tissues of the face. This unusual localization may clinically mimic nodular or cystic facial lesions having different origins. OBJECTIVE: The aim of our work was to well characterize the phenotype of the spindle cells characteristic of intramuscular mixoma. METHODS: Tissue samples were processed for morphological and ultrastructural studies. Moreover, immunohistochemical stainings were performed to characterize the expression of different nonmuscular and muscular cytoskeletal proteins. RESULTS: The tumor was composed of sparse spindle cells embedded in a prominent mucoid matrix. Besides the predominance of a fibroblast-like appearance, some neoplastic cells displayed immunohistochemical and ultrastructural features resembling either myofibroblasts or primitive mesenchymal cells, with a modulation of cell actin expression. CONCLUSION: The presence of multiple phenotypes of nonmuscular, mesenchymal pathway of differentiation can be considered a peculiar feature of intramuscular myxoma.

Facial Neoplasms↗

PubMed1995

Gastrointestinal stromal tumor: evidence for a smooth-muscle origin.

A gastrointestinal stromal tumor, arising from the rectal ampulla of a 63-yr-old man, was investigated using conventional techniques as well as Western blot analysis of its cytoskeleton proteins. The expression of desmin, muscle-specific actins, vimentin, S-100 protein, chromogranin, neuron-specific enolase, and keratins was studied using the avidin-biotin technique. The tumor cells showed a positive reaction only to antivimentin antibody. Ultrastructural analysis failed to provide conclusive evidence for neural or muscular origin of the tumor. Western blot analysis of the tumor whole-protein extract allowed identification of the presence of gamma-smooth-muscle actin, thus suggesting an enteric smooth-muscle origin of the tumor. This result seems partially to support a parenchymal smooth-muscle origin for S-100 protein and desmin-negative gastrointestinal tumors.

Actins↗

PubMed1994

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.

Adult↗

PubMed1994

Punctate porokeratotic keratoderma--its occurrence with internal neoplasia.

Punctate porokeratotic keratoderma (PPK) represents a diffuse involvement of palms and soles by multiple, accuminate keratotic papules and plugs, histologically identified by parakeratotic cornoid lamellae. A possible association between PPK and internal malignancy has been previously noted by Herman in 1973. A patient with a 3-month history of PPK is described in which a bronchial carcinoma was recently diagnosed. This association led us to speculate that PPK could be a sign of internal neoplasia, as already established for other forms of palmoplantar keratoderma. We suggest that the presence of an underlying malignancy must be screened for when a diagnosis of PPK is proposed.

Bronchial Neoplasms↗

PubMed1994

Rat aortic smooth muscle cells isolated from different layers and at different times after endothelial denudation show distinct biological features in vitro.

Endothelial denudation by balloon injury of the rat aorta induces the development of a neointima as a consequence of the migration and proliferation of smooth muscle cells (SMCs). Initially, intimal SMCs show a dedifferentiated phenotype, which reverts to a normal differentiated phenotype after endothelial cells have resurfaced the vessel lumen. We investigated in vitro the proliferative and phenotypic features of SMCs from different layers of rat aorta isolated 15 and 60 days after endothelial denudation. Freshly isolated intimal cells 15 days after balloon injury (IT-15) appeared rounded and showed a decreased content of alpha-smooth muscle actin, smooth muscle myosin, and desmin compared with intimal cells isolated 60 days after balloon injury (IT-60). No morphological and cytoskeletal differences were observed among freshly isolated IT-60 cells and other medial populations, which included medial SMCs that underlie the intimal thickening. In culture, IT-15 cells showed increased proliferative activity both in monolayers and in free-floating collagen lattices. Decreased expression of alpha-smooth muscle actin and smooth muscle myosin was documented in IT-15 cells compared with IT-60 cells and other medial SMC populations in monolayer. Moreover, IT-15 cells suspended in collagen lattices were poor at contracting these collagen lattices compared with IT-60 and control SMCs. IT-60 cells were equivalent to control SMCs at lattice contraction except for a temporary delay at day 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

PubMed1994

Erythema multiforme during GM-CSF therapy.

A 52-year-old Caucasian man treated with granulocyte-macrophage colonystimulating factor (GM-CSF) developed a cutaneous eruption on legs and ankles with clinical and histologic features of erythema multiforme. Laboratory studies indicated that the eruption occurred at the time of peripheral blood lymphocyte recovery and that it was coincidental with serum peaks of interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6) and tumour necrosis factor-alpha. We postulate that GM-CSF provoked erythema multiforme in a predisposed individual as a consequence of either an inappropriate cytokine secretion or of an abnormal amplification mechanism following lymphocyte recovery.

Erythema Multiforme↗

PubMed1994

Homogeneous stromal cell population from normal human adult bone marrow expressing alpha-smooth muscle actin filaments.

BACKGROUND: Hematopoietic microenvironment has a crucial role homing and regulating precursor cell growth both in physiologic and pathologic conditions. Fibroblast, endothelial cells, macrophages, adipocytes, and myoid cells, are the cellular component recognized in human bone marrow cultures. The presence of myoid cells in human bone marrow has been observed during fatal life, whereas during adult life, it is strictly related to pathologic conditions. EXPERIMENTAL DESIGN: The aim of this study was to isolate a homogeneous stromal cell population. The mononuclear fraction obtained from the vertebral body of living humans was cultured without hydrocortisone and horse serum to inhibit foam cell differentiation. RESULTS: The immunocytochemistry and electron microscopy characterization indicate that the cellular population we isolated had an homogeneous "myoid" differentiation. Moreover, these cells were able to support blast cell colony formation in vitro. CONCLUSIONS: This method allowed the preparation of homogeneous myoid cell cultures depleted of other bone marrow stromal components. The isolation of a single stromal population is relevant in order to study the function of contractile filaments in allowing close-binding interactions with hematopoietic precursor cells.

Actins↗

PubMed1993

Effect of propionyl-L-carnitine in a rat model of peripheral arteriopathy: a functional, histologic, and NMR spectroscopic study.

Propionyl-L-carnitine (PLC) has been shown to exert beneficial effects in experimental models of peripheral arterial diseases, such as ergotamine-induced tail gangrene and bilateral femoral arteries occlusion in rats. These models, however, present some drawbacks. The present study was performed to determine whether repeated oral administration of PLC improves the functional, histologic, and metabolic parameters in rats with long-lasting chemically induced peripheral arteriopathy. Peripheral arteriopathy was induced by injecting Na laurate in both the femoral arteries of rats. The walking capacity of the animals (treadmill test) was evaluated at different times and up to 5 weeks after Na laurate injection. Histological examination of vessels and muscles was performed at the end of the experimental period (5 weeks). In separate experiments the level of high-energy phosphates was determined with 31P NMR methodology in the leg muscles. Injection of Na laurate impaired (p < 0.05) the walking capacity of rats, caused thickening of the intima and marked narrowing of the vasal lumen, and reduced the ATP and PCr levels in muscles by 42% and 25%, respectively. PLC given orally for 7 days at 30, 60, 120, and 250 mg/kg dose-dependently decreased the severity of walking capacity impairment by 19%, 41%, 64%, and 71%, respectively. Long-term administration (4 weeks) of PLC (60 and 250 mg/kg os) caused a significant improvement of walking capacity throughout the entire period. The improvement persisted 1 week after discontinuation of the treatment. The severity of the vascular and muscular damages was markedly reduced, particularly in animals treated with the highest dose. Alterations in ATP and PCr levels were significantly (p < 0.05) diminished by PLC (120 mg/kg os) administered daily for 15 days starting 24 hours after Na laurate injection, or for 11 days starting 4 days after Na laurate. The dextro-isomer of the compound was completely inactive, and L-carnitine improved motor performance to a much lesser degree than an identical dose of PLC. It is suggested that the activity of PLC is linked to its metabolic effects on fatty acid oxidation, with consequent preservation of high-energy phosphate levels.

Animals↗

PubMed1992

Characterisation of a human glioblastoma cell line (LI) expressing hypothalamic and pituitary hormones.

The human glioblastoma cell line LI showed morphological features typical of its neuroectodermal origin. Cells were positive by immunofluorescence to GFAP, MHC class II, and L1 determinants. Cytogenetic analysis showed the presence of a modal chromosome number of 63, ranging from 58 to 69 chromosomes (DNA index was 1.6). Northern blot analysis demonstrated the presence of mRNA transcripts specific for transglutaminase C (type II or "tissue"), growth-hormone releasing-hormone (GHRH), insulin-like growth factor II (IGF-II), and proopiomelanocortin (POMC). The GHRH mRNA was present in two different sizes, one similar to the normal hypothalamic species of 0.75 kb, whilst the second species was a large transcript of approximately 10 kb size. Treatment with 5 microM retinoic acid or 5 mM alpha-difluoromethylornithine for 5 days sharply reduced the growth rate and also induced modulation of the ultrastructure and antigenic profile. This cell line may be useful to study glial differentiation and the relationship of GHRH, IGF-II and POMC expression with differentiation in neuroectodermal tumours.

Blotting, Northern↗

PubMed1992

Densitometric and morphometric study of immunocytochemical estrogen receptors detection in breast carcinomas.

Immunohistochemical quantitative evaluation of estrogen receptors (ER) detected in tissue sections from 30 breast tumors by monoclonal antibody was performed using a densitometric method. In particular, ER concentration was calculated by nuclear mean optical density (nMOD), while heterogeneity in ER content was calculated by the coefficient of variation (CV) of the nuclear optical density histogram. Tumors which showed more than 60% of positive cells had a mean value of ER-nMOD of 0.116 +/- 0.002 a.u. and of ER-CV of 33.74 +/- 0.68. Tumors which showed 30% to 60% of positive cells had a mean value of ER-nMOD of 0.082 +/- 0.006 a.u. (arbitrary units) and of ER-CV of 36.25 +/- 3.44. Tumors showing less than 30% of positive cells had ER-nMOD of 0.052 +/- 0.009 a.u. and ER-CV of 48.49 +/- 5.61. These results indicate that the greater the concentration the lower the ER heterogeneity within the tumor sample. No significant differences between ER-ICA results, nuclear size and form factors were found.

Breast Neoplasms↗

PubMed1992

Age-related modification of average volume and anisotropy of vascular smooth muscle cells.

The aim of this study was to determine what changes in the arterial wall are related to age. In two groups of rabbits, one young and one adult, the aorta and carotid were studied using a morphometric approach based on stereological axioms and planimetric morphometry. The problem of anisotropy of smooth muscle cells is discussed in detail. Two forms of anisotropy must be distinguished, that of single cell and that due to the histological pattern of the smooth muscle cells in the arterial wall. Our results show in adult animals, as compared to the young ones, statistically significant decrease in anisotropy of the cell pattern which tends to become more regular. Moreover, in aorta and carotid of young and adult animals there is an increment of 95.39% and 80% of the absolute cell volume, respectively. We suggest that there may be a direct relationship between aging and phenotypical modulation of the smooth muscle cells and that the modification of the architectural cell pattern with age may represent an adaptive event related to the change in forces acting upon the arterial wall.

Aging↗

PubMed1992

Age-dependent increase of rabbit aortic atherosclerosis. A morphometric approach.

Aging has been indicated as one of the major risk factors for development of atherosclerotic lesions, although the role aging plays, lacks accurate evaluation. Our study was aimed at quantitatively defining such a role by using morphometric analysis. Aged (median age 3 years and 8 months) and young (4 months) white New Zealand rabbits received a hyperlipemic diet enriched with a low dose of cholesterol for 16 months. At regular intervals, levels of serum lipemic parameters were checked. A Quantimet 920 image analyzer was used on paraffin-embedded sections of the entire aortas to measure the volume density of the tunica intima, the volume density of atheroma, the ratio intima/media and the surface area of the tunica intima. Our results indicated for aged hyperlipemic rabbits a statistically significant increase in all morphometric parameters examined as compared to young hyperlipemic animals, and no statistically significant differences in serum cholesterol, triglycerides and phospholipids.

Aging↗

PubMed1991

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.

Aging↗

PubMed1991

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.

Animals↗

PubMed1991

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.

Aged↗

PubMed1990

High-dose synthetic progestogens inhibit foam and smooth muscle cell proliferation and atherosclerotic plaque formation in aortas of rabbits fed a hypercholesterolemic diet.

Female rabbits on a hypercholesterolemic atherogenic diet were treated with high doses of the synthetic progestogens norethisterone and medroxyprogesterone acetate in order to clarify the effect and possibly some of the mechanism of action of these hormones on diet-induced atherogenesis. We employed morphometric studies to determine the surface area of the rabbit aorta occupied by and the maximum thickness of lipid plaques. Autoradiography with tritiated thymidine was performed to demonstrate the effect of the progestogens on cell proliferation, which plays a key role in atherogenesis. Medroxyprogesterone acetate-treated and, above all, norethisterone-treated animals exhibit a more marked reduction of atherosclerosis than control rabbits fed the same diet. Our results suggest that both progestogens we used inhibit the development of atherosclerosis mainly by blocking the proliferation of smooth muscle cells in the tunica media and the cell population of the plaque.

Animals↗

PubMed1990

Morphometric evidence of the trophic effect of L-carnitine on human skeletal muscle.

We investigated the effect of long-term i.v. administration of L-carnitine on human muscle fibers using morphometric parameters. We administered 2g/day L-carnitine to patients undergoing hemodialysis for at least 12 months. At the end of this period a marked increase in serum and muscle carnitine levels was observed in all patients, together with hypertrophy and predominance of type 1 fibers. L-carnitine was withheld for 4 months, during which time serum and muscle levels gradually decreased and no changes were observed in muscle fibers. Subsequent addition of L-carnitine to dialysis fluid for another 4 months stabilized lower levels. At the end of this period reduction of diameter of type 1 fibers was observed. Type 2 fibers remained unchanged. Moreover, type 1 fibers remained predominant in all cases. Hence, we suggest that carnitine has a specific trophic effect on type 1 fibers which are characterized by an oxidative metabolism.

Aged↗