Angiogenesis during tumor progression in human malignant melanoma.
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Blood Vessels↗
Biomedical subjects
F Dammacco
Publications and source records attributed to F Dammacco.
Differential isotype expression and binding properties of T cell-reactive antibodies in human immunodeficiency virus (HIV) infection.
Isotype and binding characteristics of T cell-reactive antilymphocyte antibodies (ALA) were investigated in 287 human immunodeficiency virus (HIV)+ sera from patients with CDC II to IVC clinical disease. Using purified soluble T-lymphoblast (CEM cell line) membranes and an ELISA method, 29 HIV+ sera showed significant reactions with this substrate and a selective expression of IgG-ALA was detected in 7 HIV+ sera. Subsequent microcytotoxicity assays, utilizing peripheral T lymphocytes and CEM cells as targets, demonstrated no significant cytotoxic capability in such sera, whereas 12 of 17 HIV+ serum samples with IgM-ALA ELISA reactivities showed a significant degree of killing in the Terasaki test. Further experiments of saturation of CD4 molecules on CEM extract by OKT4 monoclonal antibody (MoAb) induced a high inhibition of IgG-ALA binding to the T-cell membranes in only two IgG-ALA+ sera (No. 93, CDC III; No. 179, CDC II stage). Conversely, treatment of CEM membrane lysate with Leu3a MoAb, specific for the gp120 reactive domain of the HIV receptor, failed to prevent membrane binding in all seven of the IgG-ALA+ sera. Following the adsorption of serum 93 on a T-cell membrane antigen affinity column, SDS-PAGE analysis demonstrated that the predominant ALA material reacting with T-cell membranes was IgG with no detectable traces of IgM. These data provide evidence that ALA in HIV+ patients may be simultaneously or selectively expressed as IgG and/or IgM with different properties.(ABSTRACT TRUNCATED AT 250 WORDS)
Autoantibodies↗
Effects of cefodizime on non-specific immune functions in patients with multiple myeloma.
The effects of cefodizime (CDZ) on non-specific immunity in patients with multiple myeloma were studied in a randomized, placebo-controlled trial. A total of 51 patients with newly diagnosed multiple myeloma were admitted to the study, 27 of whom received CDZ 2 gi.v. once daily for seven days and 24 ascorbic acid 1 g daily i.v. for one week. Granulocyte chemotaxis, neutrophil biochemiluminescence and phagocytosis were determined at baseline, and at 48 h after the last dose. At baseline, chemiluminescence, phagocytosis and, to a lesser extent, granulocyte chemotaxis were diminished in both patient groups compared to healthy volunteers. After treatment, a significant increase in chemiluminescence and phagocytosis was observed in the CDZ group, while a slight increase in granulocyte chemotaxis did not reach statistical significance. No changes were observed in the control group. It is concluded that CDZ enhanced non-specific immune mechanisms in patients with multiple myeloma.
Aged↗
A method for detecting specific anti-C100 protein antibodies of IgM isotype in hepatitis C virus infection.
A method for the determination of specific IgM antibodies to C100 protein, a hepatitis C virus-associated antigen, was developed which employed fractionation of serum proteins by gel chromatography and an enzyme-linked immunosorbent assay. Detection of IgM anti-C100 proved to be specific and reproducible in purified IgM fractions. Separation of IgM from IgG was necessary before IgM could be measured, because of the detrimental effect of the simultaneous presence of IgG antibodies with anti-C100 rectivity on IgM determination. IgM anti-C100 was not found in sera containing rheumatoid factors or IgM antibodies to other hepatotropic viruses. IgM anti-C100 was detected in 19 (44%) of 43 patients with hepatitis C virus-related chronic liver disease. When compared with the histological picture of liver disease, IgM anti-C100 was absent in patients with minimal changes and was most common (66.7%) in patients with progressive disease. It is suggested that IgM anti-C100 could reflect an active state of hepatitis C virus infection.
Adolescent↗
Circulating levels and liver tissue distribution of intercellular adhesion molecule-1 during beta-interferon therapy of hepatitis C virus-associated chronic active liver disease.
Intercellular adhesion molecule-1, an immunoglobulin supergene family member, is known to account for important steps in cell activation and the immune response. By a non-isotopic slot-dot immunoblotting assay, we measured circulating levels of intercellular adhesion molecule-1 in 26 patients with hepatitis C virus-associated chronic active liver disease before and after beta-interferon therapy, in 6 patients with non-A, non-B acute self-limiting hepatitis and in 13 healthy subjects. Circulating intercellular adhesion molecule-1 was found in 10 of 13 (77%) normal controls at low concentrations which were not statistically different from those measured in patients with hepatitis C virus-associated chronic active liver disease responsive to beta-interferon, whereas significantly higher levels were found in unresponsive patients. Higher serum intercellular adhesion molecule-1 levels were found in 4 of 10 (40%) beta-interferon-responsive patients compared with 13 of 16 (18%) unresponsive patients. Intercellular adhesion molecule-1 levels persisted after discontinuation of beta-interferon treatment and did not correlate with hepatocytolysis (as indicated by alanine aminotransferase serum activity) either in chronic active liver disease or acute hepatitis. However, a good correlation was found between intercellular adhesion molecule-1 and its expression on liver cells, thus emphasizing that induced circulating levels may reflect the state of activation at the sites of the inflammatory process. These data strongly support the view that intercellular adhesion molecule-1 plays an important role in liver cell damage in hepatitis C virus-associated acute and chronic liver disease, and that its circulating levels may be a good prognostic parameter of responsiveness to beta-interferon therapy.
Acute Disease↗
Antibodies to hepatitis C virus in essential mixed cryoglobulinaemia.
Although essential mixed cryoglobulinaemia (EMC) is recognized to be frequently associated with chronic liver disease, aetiology and pathogenesis of liver damage remain unsolved questions. The purpose of this study was to assess the possible causative role of hepatitis C virus (HCV) in the liver impairment occurring in patients with EMC. Twenty-six consecutive EMC patients were evaluated. All patients underwent percutaneous liver biopsy. Anti-HCV antibodies were assayed by ELISA and supported by a recombinant immunoblotting assay (4-RIBA). The prevalence of anti-HCV antibodies in patients with and without chronic active liver disease (CALD) was compared. Anti-HCV antibodies were detected in 13 patients (50%) by ELISA and confirmed in 11 of them (42.3%) by 4-RIBA, the remaining two patients being indeterminate in the supportive assay. CALD correlated significantly with anti-HCV antibodies: indeed, 7/11 (63.6%) anti-HCV+ patients showed histological and clinical pictures of CALD, compared with 1/15 (6.6%) anti-HCV- patients (P less than 0.01). With the exception of the patient who was found to be HBsAg+, no liver tissue expressed hepatitis B virus-related antigens in the hepatocytes. Additional histological findings included discrete lymphoid aggregates in portal tracts, siderosis, fatty changes, hyperplasia of Kupffer cells. It can be concluded that chronic liver damage in EMC is frequently associated with anti-HCV antibodies. Although the cause of EMC remains unknown, this study has obvious implications for clarifying the etiology of associated CALD and further supports the therapeutic use of interferons in this disease.
Adult↗
Hepatitis-C-virus-related chronic liver disease of sporadic type: clinical, serological and histological features.
Hepatitis C virus (HCV) is the most important cause of transfusion-related non-A, non-B hepatitis. It is also thought to be the prime cause of non-transfusion-related or sporadic chronic liver disease. To assess the extent of HCV infection and its significance in this last form, we evaluated the clinical, serological and histological features of 84 consecutive HCV-related patients without a history of blood or blood products transfusion, alcohol or intravenous drug abuse or other known risk factors. Our results indicate that 68 patients (81%) had signs of chronicity, and 33 (39.2%) had superimposed cirrhosis. Serum abnormal alanine aminotransferase and gamma-glutamyltransferase activities represented good predictive markers of liver histological signs of chronicity. The levels of serum gammaglobulins were found to parallel histological severity of liver disease. One or more hepatitis B virus (HBV)-associated markers were present in 52 patients (61.9%). Only 6 (7.1%) were chronic HBV carriers, and 3 of them had signs of active virus replication. These data indicate that HCV plays a major role in the etiology of sporadic chronic liver disease. Its presence is associated with histological forms of chronic liver disease in most patients, who likely represent chronic HCV carriers.
Alanine Transaminase↗
Immunochemical and functional characterization of anti-idiotypic antibodies to a mouse anti-CD4 monoclonal antibody.
Immunization of BALB/c mice with the mouse anti-CD4 monoclonal antibody (mAb) HP2/6 resulted in the production of anti-idiotypic antibodies. Analysis of the kinetics of the development of anti-idiotypic antibodies showed a homogeneous response among the immunized animals. Cross-blocking assays performed with anti-CD4 mAbs OKT4, OKT4c and OKT4d showed that syngeneic anti-idiotypic antiserum elicited with mAb HP2/6 recognizes idiotope(s) expressed only on the immunizing mAb. The idiotope(s) is (are) located within or closely related to the antigen-combining site of mAb HP2/6. Hybridization with the myeloma cell line NSO of splenocytes from a BALB/c mouse hyperimmunized with mAb HP2/6 generated the anti-idiotypic mAbs F11-2113, F11-2302 and F11-2444 which recognize idiotope(s) outside the antigen-combining site of mAb HP2/6. Although the anti-idiotypic mAbs cross-inhibit each other in their binding to mAb HP2/6, they differ in the ability to elicit anti-anti-idiotypic antisera. Furthermore, mAb F11-2113 enhances CD4 down-regulation in the presence of mAb HP2/6 to a larger extent than mAbs F11-2302 and F11-2444. The latter results suggest an additional mechanism by which anti-idiotypic antibodies may induce functional abnormalities of CD4+ T cells in human immunodeficiency virus-infected T cells.
Animals↗
A rapid direct microwave irradiation technique for demonstrating hepatitis C virus-associated C100 protein in formalin-fixed liver tissue.
Hepatitis C virus-associated C100 protein was demonstrated in formalin-fixed, paraffin-embedded liver tissue from seven patients with non-A, non-B post-transfusion-related chronic liver disease, using a monoclonal antibody, biotin-streptavidin immunostaining and microwave irradiation. C100 antigen expression was limited to hepatocyte cytoplasm but was found in cells with morphological evidence of virus-induced damage and in apparently healthy cells. Positive cells were scattered throughout lobules and cirrhotic nodules with no special relation to vascular or portal structures. No staining was found in bile duct epithelium and sinusoidal cells. The method is suitable for both retrospective studies and diagnostic purposes.
Antigens, Viral↗
Parallelism of serum anti-F(ab')2 and anti-cationic IgG reactivities in patients with systemic lupus erythematosus.
Cationic anti-DNA antibodies may be related to glomerular injury in murine lupus nephritis or in patients with systemic lupus erythematosus (SLE). Therefore, anti-cationic antibodies in SLE could include antibodies with regulatory function on such pathogenic cationic molecules. Since anti-F(ab')2 antibodies may be involved in the idiotype control of anti-DNA antibodies in some patients with inactive SLE, the present study was aimed to determine if SLE patients with significant serum levels of anti-F(ab')2 produce antibodies reacting with cationic IgG molecules. Three SLE sera with high titers of anti-F(ab')2 antibodies were individually adsorbed by sequential affinity chromatography on three Sepharose columns coupling normal IgG from Cohn Fraction II, pooled cationic IgG myeloma paraproteins displaying idiotypic anti-DNA markers (F4 and 8.12), and F(ab')2 fragment from allogeneic IgG, respectively. Eluates obtained from cationic IgG adsorption showed predominant anti-F(ab')2 reactivity. A similar profile was also detected in a serum from a normal control donor with high levels of anti-F(ab')2. Biotinylation of anti-cationic eluates showed that such antibodies were significantly more reactive with cationic than anionic or neutral IgG, confirming their apparent affinity for positively charged antigens on IgG molecules. Since anti-cationic absorptions were able to remove the anti-F(ab')2 activities in the SLE sera studied, it is possible that anti-cationic antibodies could function as immunoregulatory antibodies in the idiotypic control of some SLE autoreactive phenomena, including glomerular anti-DNA deposition.
Adult↗
Monoclonal antibodies against human anti-F(ab')2 antibodies react with light chain epitopes.
Anti-F(ab')2 antibodies affinity isolated from sera of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or normal SLE relatives were used to produce monoclonal antibodies (mAbs) in Balb/c and NZB mice. Four of five mAbs showed only primary light chain specificity. Only one mAb produced in an NZB mouse against anti-F(ab')2 from a single SLE patient showed anti-mu-chain specificity. Parallel identical control immunizations with IgG or a single human IgG kappa myeloma produced mAbs with a predominant gamma-chain/Fc fragment specificity. Anti-light chain specificity of mAbs was demonstrated to involve epitopes requiring tertiary structure of the entire light chain instead of antigens confined to Ckappa/lambda or Vkappa/lambda fragments. Anti-kappa specificity of three mAbs was extremely similar but not identical to that defined by anti-Km1 allotyping systems. No evidence was obtained with any of the mAbs produced for antigens unique to SLE or RA anti-F(ab')2 antibodies. The light chain antigenic prominence of many anti-F(ab')2 antibodies may reflect structural features shared by this group of immunoglobulins somehow important for their biologic function.
Animals↗
Screening of diabetic children for coeliac disease with antigliadin antibodies and HLA typing.
IgA and IgG antigliadin antibodies were measured in 498 patients with insulin dependent diabetes mellitus and no history of intestinal malabsorption. Thirty patients had abnormal concentrations of antigliadin antibodies; 22 of these had an intestinal biopsy carried out and 16 of the 22 had subtotal villous atrophy suggestive of coeliac disease (prevalence 3.2%). There were no significant differences between patients with coeliac disease and diabetes and diabetic patients with normal IgA antigliadin antibodies in any of the nutritional variables measured, duration of diabetes, and mean insulin requirement. The mean age of onset of diabetes and attainment of expected height for age were both significantly lower in the patients with both diseases. Typing HLA classes I and II was done in 242 patients. The incidence of HLA-B8, DR3, and DQW2, which are commonly associated with both the diseases, is increased when both are present.
Adolescent↗
Kinetics of anti-hepatitis C virus response during acute hepatitis in an immunosuppressed HCV chronically infected patient.
A hepatitis C virus (HCV) chronically infected patient developed an episode of acute hepatitis during the course of immunosuppressive therapy given for a lymphoproliferative disease. It was noted that anti-HCV antibody response, seen to be relatively stable during the follow-up, lowered dramatically in coincidence with the hepatocytolytic peak. A diagnostic liver biopsy taken at the time of the acute phase of hepatitis demonstrated a typical feature of lobular hepatitis with widespread lymphocytic infiltrates, the predominant type of which expressed CD8 immunophenotype. Cytotoxic and immunosuppressive drugs may interfere with hepatitis virus infections. However, at variance from hepatitis B virus infection in which acute liver decompensation develops after withdrawal of chemotherapy in our HCV chronically infected patient it appeared during the course of the treatment, suggesting a different hepatocytolytic mechanism. Although the actual frequency of the phenomenon is presently unknown, this observation seems to indicate that immunosuppressive and cytotoxic agents should be used with caution in HCV chronic infection in which cell-mediated immune response seems to play a major role in the production of the liver damage.
Acute Disease↗
Multiple myeloma: VMCP/VBAP alternating combination chemotherapy is not superior to melphalan and prednisone even in high-risk patients.
The efficacy of alternating vincristine, melphalan (M), cyclophosphamide, prednisone/vincristine, carmustine, doxorubicin, and prednisone (VMCP/VBAP) polychemotherapy was compared with the M and prednisone (MP) regimen as induction treatment in multiple myeloma (MM). Three hundred four MM patients entered this study between March 1983 and July 1986; the analysis was performed in December 1989. The treatment groups did not show significant differences with respect to major prognostic factors. Median overall survival was 33.8 months. In the VMCP/VBAP and MP arms, after 12 induction chemotherapy cycles, 59.0% and 47.3% (P less than .068) of the patients achieved an M component reduction greater than 50%. No significant difference was observed in the two treatment arms in terms of remission duration (21.3 v 19.6 months, P less than .66) and survival (31.6 v 37.0 months, P less than .28). Patients younger than 65 years did not show any advantage from the alternating polychemotherapy. At diagnosis, the plasma cell labeling index (LI) and serum beta-2 microglobulin (beta 2-m) were evaluated in 173 and 183 patients, respectively. A significantly reduced survival was observed for patients with LI greater than or equal to 2% (16.4 months) or beta 2-m greater than or equal to 6 mg/L (20.4 months). Even in these poor-risk subgroups, VMCP/VBAP was not superior to MP.
Aged↗
[Monoclonal antibodies in the diagnosis and therapy of lung cancer].
The discovery of monoclonal antibodies (MoAbs) by Köhler and Milstein in 1975 has marked a fundamental step accounting for the present development of immuno-oncology. The use of MoAbs in the study of lung carcinoma has allowed to enlarge our knowledge on the biology and natural history of this tumor, on the diagnostic procedures both in vitro and in vivo, on the monitoring of patients as well as on the therapeutic potentialities. A number of MoAbs have been produced, directed either to the small cell lung carcinoma or to the other histotypes which are altogether defined as non-small cell lung carcinoma. Although these reagents are not specific sensu strictiori, their use has been shown to be of partial utility for tumor imaging by immunoscintigraphy and for immunotherapeutic procedures based on the administration of MoAbs conjugated with radioactive isotopes or immunotoxins. Several attempts are presently under way aiming at the production of MoAbs endowed with a more defined specificity and larger potentialities. In this context, a special mention deserve the so-called third-generation MoAbs, anti-idiotype MoAbs, the cocktails of MoAbs, and chimeric antibodies also termed humanized MoAbs.
Antibodies, Monoclonal↗
Anti-idiotypic monoclonal antibodies reacting with idiotope on isolated-denatured chains of an anti-CD4 monoclonal antibody.
Hybridization of a non-secreting mouse myeloma cell line NSO with splenocytes from a BALB/c mouse hyperimmunized with the anti-CD4 monoclonal antibody (mAb) HP2/6 generated the anti-idiotypic (anti-id) mAb F11-2113, F11-2302 and F11-2444, which recognize idiotope(s) (id) that are the same or spatially close to each other and are located outside the antigen-combining site of the immunizing mAb. Binding and inhibition assay showed that id are not expressed either on other mouse anti-CD4 mAb or polyclonal immunoglobulins (Ig). Western blotting analysis showed that the id defined by anti-id mAb F11-2113, F11-2302 and F11-2444 are similarly expressed on separated heavy and light chains of mAb HP2/6 and suggested they are likely to be 'sequence-dependent' since their expression is conserved following SDS and reducing reagents treatment. This finding is unique inasmuch as 'sequence-dependent' id similarly expressed on heavy and light chains have been described only on a mouse monoclonal auto-antibody with immunoregulatory properties.
Animals↗
A disturbance of the IL-2/IL-2 receptor system parallels the activity of multiple myeloma.
The IL-2/IL-2 receptor (IL-2R) system has been investigated in 64 patients with multiple myeloma (MM), 31 with monoclonal gammopathies of undetermined significance (MGUS) and 20 normal controls. The MM data were related to clinical status by comparing active disease, i.e. at diagnosis and at relapse, and stable disease, i.e. complete remission and off-treatment plateau phase. Serum and urinary values of the soluble IL-2R (sIL-2R) were significantly increased in MM patients compared with normal controls and this increase was related to activity. MM patients with active disease gave significantly higher values than those with stable disease. Compared with normal controls, enriched B cell (but not T cell) preparations from peripheral blood mononuclear cells (PBMC) showed significantly increased proportions of IL-2R+ cells in MM and MGUS. However, the highest proportions were detected in active MM compared with stable MM and MGUS. Also, 16% of all MM patients, as opposed to 9% of MGUS, had well-defined bone marrow IL-2R+ plasma cell populations. The lowest serum IL-2 values were found in active MM. Serial follow up of serum sIL-2R suggested that this peptide can be used as an additional marker of active malignancy. The data indicate that a disturbance of IL-2/IL-2R system is most pronounced in active MM. These findings may provide clues as to the T cell abnormalities in MM.
Aged↗
Purification of human immunoglobulins by sequential precipitation with caprylic acid and ammonium sulphate.
We have tested the usefulness of sequential precipitation with caprylic acid and ammonium sulfate to purify human monoclonal and polyclonal immunoglobulins from sera of 11 patients with monoclonal gammapathy (4 IgG kappa, 2 IgG lambda, 2 IgM kappa, 1 IgA kappa, 2 IgA lambda), four patients with autoimmune diseases and four healthy donors. In terms of purity and activity of Ig as well as execution time and cost, this two-step non-chromatographic procedure is highly efficient for the purification of IgG, IgA and IgM, thus offering several advantages over other methods of purification. Therefore, this procedure may have useful application in the preparation of human Ig for structural studies and therapeutic purposes.
Ammonium Sulfate↗