Biomedical subjects
Publications and source records attributed to M Altomonte.
Subependymomas are rare neuroectodermic tumours. The authors report a case of a patient he had a subendymoma in the left lateral ventricle, with particular attention to the MR aspects on these lesions and review of the literature.
Human endoglin (CD105) is a member of the transforming growth factor beta (TGF-beta) receptor family that binds TGF-beta1 and -beta3, but not TGF-beta2, on human endothelial cells. Immunohistochemical analyses demonstrated that CD105 is expressed on normal and neoplastic cells of the melanocytic lineage. The anti-CD105 MAb, MAEND3, stained 50, 25 and 34% of intradermal naevi, primary and metastatic melanomas investigated, respectively, and nine out of 12 melanoma cell lines. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed that CD105 expressed by melanoma cells consists of a homodimeric protein with an apparent molecular weight of 180 and 95 kDa under non-reducing and reducing conditions. Cross-linking of 125I-labelled TGF-beta1 to melanoma cells, Mel 97, by disuccinimidyl suberate (DSS) demonstrated that CD105 expressed on pigmented cells binds TGF-beta1; the pattern of binding of TGF-beta1 to melanoma cells was found to be similar to that of human umbilical vein endothelial cells. The addition of exogenous, bioactive TGF-beta1 significantly (P<0.05) inhibited the growth of CD105-positive melanoma cells, Mel 97, but did not affect that of CD105-negative melanoma cells, F0-1. These data, altogether, demonstrate that CD105 is expressed on pigmented cells and might play a functionally relevant role in the biology of human melanoma cells by regulating their sensitivity to TGF-betas.
Target of an antiproliferative antibody-1 (TAPA-1/CD81) has been shown to be non-covalently associated to HLA-DR antigens on the cell surface of B cells. In this study the authors report that triggering of CD81 by MoAb 5A6 or 1D6 significantly (P < 0.05) up-regulates the release of tumour necrosis factor-alpha (TNF-alpha) by the Epstein-Barr virus-positive (EBV)-B lymphoblastoid cell line JY. The accumulation of TNF-alpha in the culture medium of JY cells incubated with either anti-CD81 MoAb was found to be dose-dependent and similar to that obtained following crosslinking of HLA-DR antigens with MoAb L243. The effect of the combination of anti-CD81 and anti-HLA-DR MoAb on the release of TNF-alpha by JY cells was not synergistic or additive. In addition, the combination of anti-CD81 and anti-HLA-DR MoAb did not affect proliferation and homotypic aggregation of JY cells induced by each MoAb used alone. Both anti-CD81 or anti-HLA-DR MoAb induced protein tyrosine phosphorylation. However, different cytoplasmic proteins were phosphorylated following triggering of either molecule. Taken together, the data demonstrate that CD81 and HLA-DR antigens induce similar effector phenomena in the regulation of TNF-alpha release, homotypic aggregation and inhibition of JY cell proliferation.
Antibodies to the B16 melanoma cell line and to tyrosinase have been recently defined in our laboratory in sera of patients with vitiligo, melanoma, melanoma-associated hypopigmentation (MAH), and in healthy subjects. The antibody titers in each subject were measured by enzyme-linked immunosorbent assay, were compared with the mean optical density (OD) of the control group, and were expressed as relative OD. The titers of anti-B16 antibodies (relative OD +/- standard error) were 1.000 (0.058) in the controls, 1.025 (0.077) in patients with metastatic melanoma, 0.5862 (0.15) in MAH, 1.377 in surgery-induced MAH, 1.087 in vaccination with anti-idiotypic antibodies, and 2.098 (0.15) in autoimmune vitiligo. The titers in vitiligo were significantly higher (p < 0.0001) than in MAH or in healthy controls. Antityrosinase antibodies were found in titers of 1.000 (0.1024) in the controls, 1.516 (0.225) in metastatic melanoma, 1.027 (0.180) in MAH, 1.075 in surgery-induced MAH, 2.308 in vaccination-induced MAH, and 4.536 in vitiligo. Differences were found between vitiligo and MAH (p = 0.008), surgery-induced MAH (p = 0.009), vaccination-induced MAH (p = 0.059), and healthy subjects (p < 0.0001). The results of this study point to the cross-antigenicity between melanocytes and melanoma cells, and to participation of antibodies against melanoma-associated membrane antigens in the mechanism leading to the development of MAH in patients with melanoma.
Normal and neoplastic cells are protected from autologous complement (C) attack by different cell-surface C-regulatory proteins including CD59 (protectin), CD46 (membrane cofactor protein) and CD55 (decay-accelerating factor). Indirect immunofluorescence (IIF) analysis showed a differential expression of CD59, CD46, and CD55 in nine human melanoma cell lines and that the expression of CD59 was highly heterogeneous compared with that of CD46 and CD55. Levels of cell membrane CD59 were found to regulate the differential sensitivity of melanoma cells investigated to homologous C-mediated lysis; in fact, an inverse correlation (r > 0.7, p < 0.05) was found between levels of cell membrane CD59, but not of CD46 and CD55, and extent of C-mediated lysis of melanoma cells sensitized with scalar concentrations of the anti-GD3 ganglioside mAb R24. Masking of CD59 by 2.5 micrograms/ml of the anti-CD59 mAb YTH53.1 induced or enhanced C-mediated lysis of melanoma cells sensitized with 2.5 micrograms/ml of mAb R24; the latter phenomenon was found to be directly correlated (r > 0.865, p < 0.01) with levels of cell membrane CD59. CD59 is bound to melanoma cells by a glycosylphosphatidylinositol anchor: treatment of C-resistant melanoma cells Mel 97, by increasing doses of phosphatidylinositol-specific phospholipase C (PI-PLC), progressively decreased cell-surface expression of CD59 and increased C-mediated lysis of cells sensitized with mAb R24. Staining of 38 benign and malignant lesions of melanocytic origin by mAb YTH53.1 demonstrated that CD59 is consistently expressed in vivo and confirmed the heterogeneous expression detected in vitro. Our data, altogether, demonstrate that CD59 is the main restriction factor of C-mediated lysis of melanoma cells and that levels of CD59 may account for their differential resistance to C-mediated lysis. The analysis of the levels of CD59 could represent an useful strategy in selecting melanoma patients who may benefit from immunotherapeutic treatment(s) that trigger C activation.
Immunohistochemical and/or indirect immunofluorescence analysis with monoclonal antibody (MAb) H19 demonstrated the expression of protectin (CD59) in 54 surgically removed metastatic melanoma lesions and on 8 out of 12 melanoma cell lines. CD59 expression had a low degree of intra- and intertumor heterogeneity. SDS-PAGE analysis showed that the molecular weight of CD59 expressed on melanoma cells is about 20 kDa. Treatment of melanoma cells with 5U/ml of phosphatidylinositol-specific phospholipase C completely abolished cell-surface expression of CD59. Interferon-gamma and/or tumor necrosis factor-alpha or phorbol 12-myristate 13-acetate neither modulated the expression of CD59 by melanoma cells nor influenced the amounts of CD59-specific mRNA. F(ab')2 fragments of anti-CD59 MAb YTH53. I did not inhibit the lysis of melanoma cells by allogeneic natural killer (NK) cells or lymphokine-activated killer (LAK) cells. In contrast, the whole Ig molecule of MAb HI9 or YTH53.I significantly (p < 0.05) enhanced NK-cell-mediated lysis of melanoma cells, suggesting the induction of antibody-dependent cell-mediated cytotoxicity. Lastly, masking of CD59 by MAb YTH53.I or its F(ab')2 fragments significantly (p < 0.05) enhanced, in a dose-dependent fashion, the lysis of anti-GD3-sensitized melanoma cells by homologous complement. These data demonstrate that CD59 expressed by human melanoma cells might regulate host-tumor interaction by protecting neoplastic cells from complement-mediated lysis.
Acute Posterior Fossa Subdural Haematoma (PFSDH) caused by trauma is a clinical rarity: only 13 cases have been encountered in the literature. Three consecutive personal cases of PFSDH are presented. Two of them are respectively the sixth and the seventh surgically treated cases with success. Among the 16 cases 60% had a sudden clinical worsening within 24 hours. Seven cases had an occipital fracture. Of the thirteen cases operated upon 11 (85%) were in a state of deep coma. The surgical mortality was 46%. One patient had a good recovery (Grade 5) and six a moderate disability (Grade 4) on the Glasgow Outcome Scale. We conclude that surgical treatment must always be carried out even in patients presenting in an agonal state.
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Seven patients with metastatic melanoma were vaccinated with anti-idiotypic monoclonal antibody (mAb) MK2-23 which mimics the high-molecular-weight melanoma-associated antigen (HMW MAA). Sera samples were assayed for anti-anti-idiotypic antibodies, by Ab1-Ab2 complex inhibition test, for anti-B16 epitope antibodies, which are a heterogeneous group against various antigens presented on B16 melanoma cells and for anti-tyrosinase antibodies, which are specific against tyrosinase. Our results pointed to the participation of anti-tyrosinase antibodies in the immune response to vaccination by anti-idiotypic antibodies mimicking the HMW MAA. The anti-tyrosinase antibody kinetic curves presented an initial increase in titres in five cases followed by decreasing titres; in two cases a constant decrease was noted. The inhibition assay demonstrated an increasing percentage of inhibition (range 17-100%) within 100-400 days of treatment. The titre of the anti-tyrosinase antibodies increased following the vaccination, then decreased--probably due to absorption of the antibodies to melanoma cells and normal melanocytes. A positive slope in the percentage of inhibition was roughly associated with a negative slope of anti-tyrosinase antibodies. In one case, a long-standing complete clinical response was accompanied by development of melanoma-associated hypopigmentation. Anti-B16 epitope antibodies had no role in the response to vaccination. The development of anti-tyrosinase antibodies in response to vaccination by anti-idiotypic antibodies mimicking another antigen may be explained by induction of non-specific polyclonal B lymphocytes activation, a well-recognized phenomenon in autoimmune disorders.(ABSTRACT TRUNCATED AT 250 WORDS)
Typical Interhemispheric Subdural Haematomas (ISDHs) are located along the whole interhemispheric fissure. In the four cases of our series, three of which surgically treated, and in the 29 cases reported in literature ISDH has been usually encountered in elderly age (mean age 56) in most of cases following head injury. Anticoagulant therapy was a favouring factor. The source of bleeding was never demonstrated at surgery, nevertheless some authors report a parafalcic bridging-veins laceration due to a brain linear acceleration during trauma, as cause. Clinically, immediate loss of consciousness was usually absent. Focal symptoms arose within 8-48 hours after trauma. In the majority of cases with ISDH, focal symptoms have been characterized by controlateral motor palsy with crural dominance as it has been observed in the "falx syndrome". Facial palsy was absent in all cases but one. Skull fractures were rare. On CT scan ISDH was shown as a spontaneously high density parafalcic area in a flat-convex lenticular shape. In the only case studied with MRI, the site where the ISDH emerged at brain convexity from the interhemispheric fissure, has been clearly localized by means of multiplanarity reconstructions, allowed us a target surgical approach. The majority of patients underwent surgery. The overall mortality rate was 24%: 14% among the 7 cases conservatively treated and 27% among the 26 operated ones. These last patients had a good recovery in 58% and an improvement in 15%. Surgical treatment must be promt as much as possible because of the possible sudden worsening of patient clinical conditions. Craniotomy is the surgical treatment that achieved the best results, nevertheless in our opinion the additional data offered by MRI may repropose the use of target cranial burr holes.
In addition to their functional role as peptide-binding proteins HLA class II Ag can also act as signal-transducing molecules. The present study showed that cross-linking of HLA class II Ag by the anti-HLA-DR mAb L243 or by the anti-HLA-DR,-DP mAb IVA12 significantly (p < 0.05) increased the release of TNF-alpha by the EBV-B lymphoblastoid cell line JY. In contrast, the anti-HLA-DR mAb 2.06 or the superantigens staphylococcal exotoxin toxic shock syndrome toxin-1 and staphylococcal enterotoxin B that bind to HLA-DR,-DQ Ag did not affect the release of TNF-alpha by JY cells. The accumulation of TNF-alpha in the culture medium of JY cells peaked at 24 h, decreased thereafter, and was found to be dependent on the dose of mAb L243 or mAb IVA12 used to cross-link HLA class II Ag. mAb L243 or staphylococcal exotoxin toxic shock syndrome toxin-1 enhanced the spontaneous homotypic aggregation of JY cells and mediated a dose-dependent inhibition of JY cell proliferation. These phenomena were not mediated by TNF-alpha released in response to cross-linking of HLA class II Ag; polyclonal anti-TNF-alpha neutralizing antibody did not affect JY cell aggregation and the inhibition of JY cell proliferation mediated by mAb L243. In contrast, TNF-alpha secreted by JY cells enhanced a nuclear factor-kB-like activity through the binding to the 75-kDa TNF-alpha receptor. These results demonstrate an additional role of HLA class II Ag as signal-transducing molecules regulating the production of bioactive TNF-alpha by EBV-B cells. The release of TNF-alpha after the triggering of HLA class II molecules could be relevant to different aspects of B cell biology and might play a role in the pathogenesis of human diseases in which antibodies cross-reactive to HLA class II Ag have been identified.
Immunohistochemical staining with monoclonal antibodies showed a differential distribution of intercellular adhesion molecule 1 (ICAM-1/CD54) and lymphocyte function-associated antigen 3 (LFA-3/CD58) and their respective counterreceptors lymphocyte function-associated antigens 1 (LFA-1/CD11a) and 2 (LFA-2/CD2) on ten melanoma cell lines and in 46 surgically removed metastatic melanoma lesions. CD11a and CD2 were not detected on melanoma cells while CD54 and CD58 were coexpressed on the majority of the melanoma cell populations investigated. CD54 showed a higher degree of intra- and intertumor heterogeneity than CD58. gamma-Interferon and/or tumor necrosis factor alpha upregulated the expression of CD54 by melanoma cells, but neither modulated that of CD58 nor induced that of CD11a and CD2. Anti-CD54 and anti-CD58 monoclonal antibodies partially inhibited the lysis of melanoma cells by allogeneic natural killer cells, lymphokine-activated killer cells and, to a greater extent, by autologous tumor-infiltrating lymphocytes. Soluble CD54 (cCD54) purified from serum of patients with melanoma inhibited the lysis of melanoma cells F0-1 by natural killer cells in a dose-dependent fashion. These results suggest that membrane-bound CD54 and CD58 and cCD54 play a role in host-tumor interactions in patients with malignant melanoma and may account for the relationship between CD54 expression in primary lesions and the clinical course of disease.
Giant fusiform aneurysm (2.5 cm in length or more) is an unusual pathological entity typically described involving the main trunks of cerebral arteries and, rarely, cerebral artery branches. We are presenting two cases of middle cerebral artery branch giant fusiform aneurysm, one surgically and the other conservatively treated. We were unable to find in the literature reports of similar aneurysms at the same location. Clinical and pathological aspects, radiological findings, and treatment are discussed.
Fifteen consecutive cases of subdural haematomas (SDHs) of arteriolar origin operated on during the last twenty years in the Neurosurgical Clinic of the University of Genoa are reported. These SDHs are rare and form as a result of a rupture of a cortical arteriolar branch typically on the vicinity of the Sylvian fissure. They are always in a pure form and never associated with parenchymal lesions. Their aetiology is spontaneous, as in the 40% of our series, or more frequently related to minor traumas. These SDHs are often encountered in elderly patients generally presenting with severe clinical conditions (in the 60% of our patients GCS on admission was < 8). Prompt surgical treatment is required in all cases before further worsening of their neurological condition, even if CT scanning does not reveal parenchymal lesions. The mortality rate is over 50% and mainly relates to the pre-operative GC score. Clinical features, neuroradiological aspects and treatment are discussed and literature reviewed.
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17 cases of operated Posterior Fossa Epidural Hematomas (PFEDH) of traumatic origin are reported. Clinical and neuroradiological findings are presented and discussed. Authors emphasize the importance of CT scan in determining a more precise diagnosis and the related improvement in the morbidity (13%) and mortality (12%) rates.
Induction of HLA class I antigens on cultured melanoma cells FO-1 after transfection with a human or a mouse B2m gene was associated with a statistically significant reduction in their susceptibility to natural killer (NK) cell-mediated lysis. These results indicate that the structural differences between human and mouse beta 2-mu do not abolish the ability of the HLA class I molecular complex to modulate NK cell-mediated lysis of melanoma cells FO-1. The role of HLA class I antigens in the phenomenon is corroborated by the ability of anti-HLA class I MAb to enhance, although to a different extent, the susceptibility of transfected FO-1 cells to NK cell-mediated lysis. Gamma interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) significantly reduced the susceptibility to NK cell-mediated lysis of transfected FO-1 cells. Surprisingly, TNF-alpha reduced the extent of lysis more than IFN-gamma, although the latter cytokine enhanced HLA class I antigen expression more than the former one. This finding, in conjunction with a reduction in the susceptibility to NK cell-mediated lysis of untransfected FO-1 cells incubated with IFN-gamma or TNF-alpha, suggests that the two cytokines reduce NK cell-mediated lysis of transfected cells by modulating not only the expression of HLA class I antigens, but also that of other structures. Induction of HLA class I antigens and their modulation with IFN-gamma did not affect the susceptibility to lymphokine-activated killer (LAK) cell-mediated lysis of transfected FO-1 cells. Characterization of the molecular mechanism(s) underlying abnormalities in HLA class I antigen expression by melanoma cells and of the role of these molecules in the interactions of melanoma cells with various types of effector cells may suggest novel immunotherapeutic approaches to melanoma.
This study reports and discusses clinical and neuroradiological findings in 22 new cases of posterior fossa epidural hematomas (PFEDHs), all of whom underwent surgical treatment after having suffered an occipital head trauma. The authors emphasize the importance of serial CT scans in establishing prompt diagnosis and treatment and in reducing the rates of morbidity (15.7%) and mortality (13.6%).