Biomedical subjects
Publications and source records attributed to G Rossi.
We show by molecular dynamics simulations that the melting temperature of clusters can be tuned by selective doping. In fact, a single Ni or Cu impurity in Ag icosahedral clusters considerably increases the melting temperature even for sizes of more than a hundred atoms. The upward shift is correlated to the strain relaxation induced by a small central impurity in icosahedral clusters.
The body-centered-cubic (bcc) phase of Ni, which does not exist in nature, has been achieved as a thin film on GaAs(001) at 170 K via molecular beam epitaxy. The bcc Ni is ferromagnetic with a Curie temperature of 456 K and possesses a magnetic moment of 0.52+/-0.08 micro(B)/atom. The cubic magnetocrystalline anisotropy of bcc Ni is determined to be +4.0x10(5) ergs x cm(-3), as opposed to -5.7x10(4) ergs x cm(-3) for the naturally occurring face-centered-cubic (fcc) Ni. This sharp contrast in the magnetic anisotropy is attributed to the different electronic band structures between bcc Ni and fcc Ni, which are determined using angle-resolved photoemission with synchrotron radiation.
The Ras-association domain family 1A (RASSF1A) tumour suppressor gene is inactivated in a variety of solid tumours, usually by epigenetic silencing of the promoter and/or allelic loss of its locus at 3p21.3. RASSF1A induces cell cycle arrest through inhibition of cyclin D1 accumulation. In this work, 62 endocrine tumours from different sites in the gut were investigated for methylation of the RASSF1A promoter using the polymerase chain reaction, the presence of 3p21.3 deletions by loss of heterozygosity analysis, and cyclin D1 expression by immunohistochemistry. Methylation was found in 20/62 (32%) cases and was restricted to foregut tumours; deletion at 3p21.3 was found in 15/58 (26%) informative cases and restricted to malignant foregut tumours; cyclin D1 hyper-expression was found in 31/58 (53%) cases and correlated with RASSF1A methylation. Our data suggest that RASSF1A is involved in the development of endocrine tumours derived from the foregut only, and that the presence of both RASSF1A methylation and 3p21.3 deletion is associated with malignancy. These results may provide a rationale for foregut-targeted therapy for aggressive endocrine carcinomas entailing the use of demethylating agents.
In situ split liver transplants represent a technical progression from ex situ split procedures conceived to retrieve grafts for pediatric recipients. The transection line runs along the falciform ligament, so the main artery to the right graft is the right proper artery, whereas the left graft retains the main arterial axis with the celiac trunk. Although the major advantages are for pediatric recipients, due to the expanded pool of grafts available, for adult recipients the results of right split in situ grafts must be compared with whole grafts. We considered two groups of consecutive grafts transplanted since 1993 as first grafts: 20 of the former and 261 of the latter. Groups were comparable for donor gender, recipient age and gender, perfusion solution, ischemia time, and follow-up time, but not for donor age and for the number of arterial anastomoses. Although there were more major surgical complications in the former compared with the latter group (40% vs 25%), the only statistically significant difference was found in retransplantation rate for arterial complications (15% vs 2.2%). No statistical difference was observed in graft or patient actuarial survival rates at 1, 3, or 6 years after transplantation; for right split grafts these were 85%, 69%, and 69% and 95%, 79%, and 79%, respectively.
To assess the efficacy and safety of a primary immunosuppressive regimen with tacrolimus (Tac) and low-dose mycophenolate mofetil (MMF) without steroids and to determine the exposure to mycophenolic acid (MPA) in the early postoperative period, we performed a single-center, randomized 1:1, open-label, controlled study planned to be 60 liver transplantation patients randomized into 2 groups: group A, tacrolimus + MMF (750 mg orally twice a day); and group B, tacrolimus + MMF (750 mg orally twice a day) + steroids. After an interim analysis by the ethical committee patient enrollment was stopped. Data from 30 patients (12 in group A and 18 in group B with a mean follow-up period of 31 +/- 7 months) showed a patient survival rate of 91.7% in group A and 100% in group B and a graft survival rate of 91.7% and 88.9%, respectively. Nine patients (75%) in group A suffered an acute rejection episode, whereas in group B only 3 patients (16.7%) showed acute rejection (P = .002). All rejection episodes occurred in both groups at 1 week after transplantation. The difference in histological grading was statistically significant (P = .021). The toxicity profiles were similar in both groups. A primary immunosuppressive regimen based on Tac and low-dose MMF without steroids is safe but unable to prevent acute rejection at 1 week after transplantation even if early acute rejection does not affect the outcome in terms of morbidity and graft or patient survival.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Oral cavity lymphoma (OCL) seems to occur more frequently in HIV-positive patients, but it is presently unknown whether HIV-related immune deficit plays a role in modifying the prevalence and the characteristics of these lymphomas. To clarify this issue, we compared OCL occurring in immunocompetent and HIV-positive patients. A comparison was made between cases of OCL occurring among 543 and 123 NHL consecutively diagnosed at a single center in immunocompetent and HIV-positive patients respectively. The prevalence of oral cavity involvement at diagnosis was significantly lower in the immunocompetent subgroup (HIV-negative: 1.66%; HIV-positive: 7.3%, P = 0.002). Extranodal T/NK nasal-nasal-type lymphoma (ET/NK-NL) was observed in 3 of 9 immunocompetent patients, whereas plasmablastic lymphoma (PBL) was observed in 3 of 9 HIV-positive patients. EBV expression correlated with HIV-positivity. Response to treatment was similar between the two subgroups, but the overall prognosis was significantly worse among HIV-positive patients. Median survival was 34 months in immunocompetent vs. 9 months in HIV-positive patients (P < 0.01). A higher frequency of oral cavity lymphoma was associated with HIV infection. ET/NK-NL and PBL seemed to be clinical entities characteristically related to immunocompetent and HIV-positive subgroups, respectively. Chemotherapy was feasible and effective in both subgroups, although a poor prognosis was associated with immunodeficiency.
The Muir-Torre syndrome (MTS) is an autosomal dominant genodermatosis characterized by the presence of sebaceous gland tumours, with or without keratoacanthomas, associated with visceral malignancies. We describe and characterize two families in which the ample phenotypic variability of MTS was evident. After clinical evaluation, the skin and visceral tumours of one member of a family with 'classic' MTS and one member of a family with a 'peculiar' MTS phenotype without sebaceous lesions, but with only multiple keratoacanthomas, were analysed for microsatellite instability (MSI) and by immunohistochemistry. Tumours of both individuals showed MSI, with a concomitant lack of MSH2 immunostaining in all evaluated skin and visceral lesions; moreover, in the proband of family 2 a constitutional mutation (C-->T substitution leading to a stop codon) in the MSH2 gene was identified. We conclude that the diagnosis of MTS, which is mainly clinical, should take into account an ample phenotypic variability, which includes both cases with typical cancer aggregation in families and cases characterized by the association of visceral malignancies with multiple keratoacanthomas (without sebaceous lesions), without an apparent family history of cancer.
AIMS: To investigate the value of platelet-derived growth factor receptors (PDGFRs) by immunohistochemistry in discriminating KIT-negative gastrointestinal stromal tumours (GISTs) from other soft-tissue neoplasms of the digestive tract. METHODS AND RESULTS: One-hundred and sixty-seven primary gastrointestinal mesenchymal tumours (125 GISTs, 15 intra-abdominal desmoids, 12 leiomyomas, eight leiomyosarcomas, three schwannomas, two solitary fibrous tumours, and one case each of inflammatory pseudotumour and fibroid polyp) were reclassified based on morphology and on the immunohistochemical panel recommended by the National Institutes of Health consensus on GIST. All cases were then tested with antibodies specific for PDGFR alpha and beta. Of 125 GISTs, 117 were KIT-positive (93.6%) and eight KIT-negative (6.4%). All the KIT-positive GISTs were negative for both PDGFRs, while all the eight KIT-negative GISTs expressed PDGFR-alpha, with two of them also coexpressing PDGFR-beta. Among the 42 non-GIST tumours, only a small percentage (26.6%) of desmoids immunostained for PDGFR-alpha, two of them coexpressing PDGFR-beta. CONCLUSIONS: Immunostaining with PDGFR-alpha is a helpful marker in discriminating between KIT-negative GISTs and other gastrointestinal mesenchymal lesions: all KIT-negative GISTs were positive for PDFGR-alpha, while none of the other gastrointestinal mesenchymal tumours analysed, except a small subset of desmoids, was reactive with anti-PDGFRs. These preliminary data demonstrate the suitability of commercially available antibodies to detect immunohistochemically the mutually exclusive expression of KIT and PDGFR-alpha previously reported in GISTs by molecular biological techniques. Since PDGFR exists in the form of a homodimer (alphaalpha, betabeta) or heterodimer (alphabeta) and two of the KIT-negative GISTs coexpressed both PDGFR isoforms, further investigations are required to elucidate the role of PDGFR-beta in GISTs.
OBJECTIVES: High levels of plasma high sensitivity C-reactive protein (CRP), sensitive to therapy with statins, have been described in hypercholesterolaemia. In vitro evidence shows that CRP activates the complement system, which, in turn, leads to an increased expression of ICAM-1. Our objectives were to verify whether primary hypercholesterolaemia (PHC) is associated with an upregulation of the inflammatory/immune response, and whether this is sensitive to atorvastatin. METHODS AND RESULTS: We examined the levels of sICAM-1, C3, C4 complement fractions in 48 patients with PHC, with (CAD group) or without (No-CAD group) coronary artery disease (CAD) in comparison with a group of 48 healthy controls. The two patient groups were studied before and after atorvastatin therapy. Both hypercholesterolaemic groups showed higher mean values of sICAM-1, C3 and C4 (P < 0.0001) when compared with the controls. The two groups of patients responded differently to atorvastatin therapy. After 3 months, the C3 levels normalized in both groups of patients (P < 0.02 compared with basal values); C4 was greatly reduced only in the CAD group (P < 0.01). After 12 months of therapy, in CAD group C3 mean levels were still significantly lower than baseline values (P < 0.01); a further decrease in the C4 values (P < 0.05 with respect to levels after 3 months of therapy) and also a substantial reduction in sICAM-1 values (P < 0.001 with respect to basal values) were observed. CONCLUSIONS: High plasma values of C3 and C4 in PHC cluster with high values of sICAM-1, distinguish subjects with CAD and could be used to monitor the anti-inflammatory effect of statin therapy in these patients.
The expression of cytokeratins in gastrointestinal stromal tumours (GISTs) is rare and may lead to diagnostic confusion when it occurs. This report describes a metastatic GIST that stained strongly for cytokeratins, CD117, and CD34 in a patient who was previously diagnosed with gastric epithelioid angiosarcoma. A review of both tumours showed the same histological and immunohistochemical profiles, and c-kit molecular analysis revealed an insertional mutation at codon 558 of exon 11 in both tumours. Thus, pathologists should be aware that GISTs can occasionally express cytokeratins, and that c-kit mutational investigations may have a key diagnostic role and may prevent diagnostic mistakes that could have important clinical implications.
Endoglin (CD105, an accessory component of the TGF-beta receptor complex) expression and distribution on different human tumour cells and its role in cellular proliferation were evaluated. We examined: 1) sixteen human carcinoma cell lines, 2) eight human sarcoma cell lines, 3) five miscellaneous tumour cell lines. HECV (endothelial cells) were employed as a positive control for endoglin expression. Normal Human Dermal Fibroblasts (NHDF) and 293 cells (epithelial kidney cells) were used as normal controls for connective and epithelial tissues, respectively. The results showed that CD105 was poorly expressed in the majority of human carcinoma cells (10/16), whereas it was highly expressed in most human sarcoma cells (7/8), and differently expressed by miscellaneous tumour cell lines. These data reflect endoglin expression by the normal counterparts of tumour cell lines, i.e. NHDF and 293 cells. However, CD105 levels in sarcoma cell lines, even though consistently lower than in NHDF, were significantly higher than those observed in carcinoma cells. Interestingly, CD105 presented a strong expression in the cytoplasm of MDA-MB-453 (breast carcinoma), NPA (papillary thyroid carcinoma), COLO-853 (melanoma) and SaOS-2 (osteosarcoma), but was weakly expressed on their cell membrane. This differential expression in the cytoplasm and on the membrane of some tumour cells, suggests a complex mechanism of translocation for this protein. The analysis of clonal growth in soft agar of some cell lines, characterized by high CD105 expression, showed an increased colony formation potential that was antagonized by the addition of anti-CD105 blocking mAb. The results indicated that endoglin is differentially expressed in human carcinoma and sarcoma cells and its overexpression modulates the proliferative rate of human solid tumour cells. Moreover, these data suggest that CD105 is involved in the regulation of TGF-beta effects in human solid malignancies, and therefore it could play an important role in tumour diagnosis and treatment.
In vitro growth culture systems of mammalian oocytes have been developed with the aims of studying regulative processes occurring during oogenesis and folliculogenesis, and of preserving fertility. Although in large mammals IVG technology does not still assure the co-ordinate development of both somatic and germinal cells and the production of high number of viable offspring, their improvement may represent an important therapeutic tool for restoring fertility in women undergoing premature menopause or cancer treatments. Morphological studies of in vitro grown follicles were not performed extensively, especially by means of scanning electron microscopy. In the present paper preliminary ultrastructural observations of in vitro cultured follicles are presented.
AIM: Sickle cell disease has been frequently associated with sensorineuronal hearing loss. Several studies have demonstrated a significant prevalence rate of sensorineuronal hearing loss in black patients reporting a range of 11-41%, while few data are reported for white people with Hb S/beta thalassemia. In this paper we evaluated the prevalence of sensorineuronal hearing loss in a Sicilian population affected by sickle cell disease. METHODS: Otologic and audiologic examinations were performed in 50 patients with S-beta thalassemia (37 with the beta(s)beta(0th) and 13 with the beta(s)beta(+th)) and 23 patients with sickle cell anemia (beta(s)beta(s)) observed at the Department of Pediatric Hematology and Oncology, University of Catania. RESULTS: A sensorial hearing loss of more than 25 dB was recorded in 24% of subjects with Hb S/beta0-thalassemia, in 23% of subjects with Hb S/beta+-thalassemia and in 30% of subjects with sickle cell anemia. We found an increase in the frequency of hearing loss with increasing age. CONCLUSIONS: Our data showed that sensorineuronal hearing loss is a common complication in white patients with sickle cell anemia, and in patients with severe forms of Hb S/beta-thalassemias.
Maedi visna virus (MVV) vertical transmission in sheep via infected colostrums is a very important route of infection in lambs. To verify colostral transmission and to study early viral entry in lambs, colostrum samples, and small intestine and mesenteric lymph nodes of lambs born from experimentally infected ewes were examined by histopathology, immunohistochemistry (IHC) and in situ hybridisation (ISH) studies. In particular, newborn lambs were naturally fed maternal colostrum and humanely killed at 10, 24, 48, 72, 96 h and 7 and 10 days after birth; two caesarian-derived lambs served as uninfected controls. No lesions suggestive of MVV infection were found, but marked immunoreactions for MVV capsid antigen (CA, p28) were detected in lambs fed maternal colostrum and in macrophages cultured from colostrum. IHC results in lambs suggest an initial viral absorption by intestinal epithelial cells at the tip of the villi, passage to mononuclear cells in the lamina propria and involvement of ileum Peyers' patches and mesenteric lymph nodes, with different staining patterns depending on infection times. ISH on intestinal sections of the 72 h lamb revealed the presence of proviral DNA in epithelial cells at the tip of the villi, suggesting a role for these cells in early MVV replication. The results contribute to knowledge about the pathogenesis of ovine lentivirus infection suggesting that the small intestine and mesenteric nodes are the sites of entry and propagation of MVV in lambs fed colostrums from infected ewes.
Three members of an Italian family with autosomal dominant dementia and multiple strokes had the A713T mutation of the APP gene. The neuropathologic examination of the proband disclosed Alzheimer disease (AD) with severe cerebral amyloid angiopathy and multiple infarcts. This indicates that the A713T mutation of the APP gene, lying at the gamma-secretase cleavage site, can be responsible for AD with symptomatic cerebral amyloid angiopathy.
BACKGROUND: In this study, we compared the relative ability of FSH (100 mIU/ml), epidermal growth factor (EGF) (10 ng/ml), and follicular-fluid meiosis-activating sterol (FF-MAS, 10 micromol/l) to induce meiotic resumption and polar body I (PBI) extrusion in mouse oocytes. METHODS: Cumulus-enclosed oocytes (CEO) were co-incubated with meiosis-arresting agents, including 4 mmol/l hypoxanthine (Hx), 0.3 mmol/l dibutyryl cAMP (dbcAMP), and 8.5 micromol/l cilostamide, a selective inhibitor of the oocyte-specific phosphodiesterase 3 (PDE 3). RESULTS: In Hx-treated oocytes, FSH, EGF and FF-MAS induced meiosis resumption at very high rates, but only FSH and EGF also promoted PBI extrusion with high frequency. In experiments conducted in the presence of dbcAMP, FF-MAS was unable to promote an increase in germinal vesicle breakdown (GVBD) rate, whereas FSH and EGF generated a response similar to the Hx groups. Neither FSH, EGF nor FF-MAS caused any change in the meiotic status of CEO when meiotic arrest at the germinal vesicle (GV) stage was maintained by cilostamide. In the presence of Hx, naked oocytes (NkO) co-cultured with their cumulus cells were able to respond to the GVBD-inducing effect of FSH and EGF by resuming meiosis at high rate. CONCLUSIONS: Collectively, these results indicate that: (i) a signal triggered in cumulus cells by either FSH or EGF, but not necessarily coincident with FF-MAS, may contribute to meiotic maturation, supporting GVBD and extrusion of PBI; (ii) the transmission of this signal can occur in a paracrine fashion, at least with reference to the breakdown of the GV. It also appears that concomitant regulation of intra-oocyte cAMP degradation is a prerequisite for meiosis resumption.