Biomedical subjects

A Fusaro

Publications and source records attributed to A Fusaro.

At least 19 recordsLinked to original sources

PubMed1998

The effect of intestinal permeability on pancreatic enzyme-induced enteropathy in the rat.

BACKGROUND: Fibrosing colonopathy in cystic fibrosis occurs in children 2 to 7 years old and is associated with excess doses of high and regular strength lipase pancreatic enzymes, given for more than 6 months. A rat model was developed to study the effects of excessive doses of pancreatic enzymes equivalent to those producing fibrosing colonopathy in cystic fibrosis patients. METHODS: Five groups of animals were studied after administration of different combinations of pancreatic enzymes, oleic acid, and reserpine. RESULTS: Pancreatic enzymes alone produced minimal damage to the intestine and none to the liver. Excessive doses of pancreatic enzymes in combination with agents that increased intestinal permeability (oleic acid, reserpine) were associated with intestinal eosinophilia and necrosis of the jejunoileal muscle layer and inflammatory nodules in the liver, which increased with duration of insult. CONCLUSIONS: Increased intestinal permeability potentiates damage to the intestine caused by excessive pancreatic enzyme dosage. It is a characteristic of cystic fibrosis that may increase vulnerability to fibrosing colonopathy.

Animals↗

PubMed1994

Expansion of T cells expressing low CD4 or CD8 levels in B-cell chronic lymphocytic leukemia: correlation with disease status and neoplastic phenotype.

Peripheral blood (PB) T cells from 56 patients with B-cell chronic lymphocytic leukemia (B-CLL) were analyzed by two- and three-color immunofluorescence (IF) to determine the expansion of distinct T-cell subsets and their relationship with the clinical and biological features of the disease. We detected the expansion of an unusual T-cell subpopulation expressing lower CD4 or CD8 levels (CD4lo, CD8lo) than classic T cells (CD4hi, CD8hi). This subpopulation also expressed low levels of the CD3/TCR alpha/beta complex and was CD19-CD13-CD14-. A phenotypic analysis probing the activation level of CD4lo, CD8lo, CD4hi, and CD8hi cells showed that they comprised increased counts of HLA-DR+, CD11b+, CD45R0+, and CD45RA+ cells. Subset expansion ranged from 2.1- to 13.6-fold. Statistical analysis showed that the size of some of these subsets was correlated to intrinsic features of the tumor. First, CD4loHLA-DR+ cell counts were higher in patients with stage A than those with stages B and C disease. Second, CD8loHLA-DR+ cell counts were higher in patients in stable remission than in those at diagnosis. Third, CD4loHLA-DR+, CD4loCD45R0+, CD4loCD45RA+, and CD4hiCD11b+ cell counts were higher in patients whose tumor cells expressed high levels of surface immunoglobulin (sIg) than in those expressing low levels. The involvement of CD4lo and CD8lo cells in most of these correlations suggests that they may be tumor-reactive cells. Similar cells described in human and murine autoimmune disease have been shown to be autoreactive anergic cells, which may derive from nonclassic pathways of T-cell development.

Adult↗

PubMed1994

Recombinant interferon-gamma inhibits the in vitro proliferation of human myeloma cells.

Interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma) and dexamethasone (DEX) have shown anti-tumour effects in multiple myeloma (MM) cells. Bone marrow plasma cells from 39 MM patients were cultured to clarify the intensity and specific activity of each compound on bromo-deoxyuridine (BrdUrd) uptake and immunoglobulin (Ig) secretion. BrdUrd uptake was inhibited by recombinant human IFN-gamma (100 U/ml) and by DEX (10(-6) M). The stimulation index (StI), i.e. labelling index (LI) of treated samples/controls, was 0.49 +/- 0.09 (mean +/- standard error of the mean, M +/- SEM), P = 0.0003, and 0.52 +/- 0.07 (M +/- SEM), P < 0.0001, respectively. Ig secretion was reduced by IFN-alpha (100 U/ml) and DEX. The secretion index (SI), i.e. Ig quantitation of treated samples/controls, was 0.04 (M +/- SEM), P < 0.0001, and 0.52 +/- 0.04 (M +/- SEM), P < 0.0001, respectively. Finally, IFN-gamma inhibits BrdUrd uptake only and IFN-alpha secretion only. In 18 patients the simultaneous addition of IFN-alpha plus IFN-gamma mainly parallel the effect of IFN-gamma on BrdUrd uptake and IFN-alpha on secretion, but not result in any additive or synergistic effect, though both BrdUrd uptake and Ig secretion were decreased to about the same extent as with DEX. These data indicate that the combination of IFN-alpha plus IFN-gamma and DEX are the strongest inhibitors of both BrdUrd uptake and secretion. Since IFN-alpha and IFN-gamma appear to have a different mechanism of action, their combined use could be considered as a possible new treatment strategy.

Bone Marrow↗

PubMed1993

Multiple myeloma: 'early' plasma cell phenotype identifies patients with aggressive biological and clinical characteristics.

The immunological phenotype of bone marrow myeloma cells and peripheral blood lymphocytes was evaluated in 38 untreated myeloma patients. A striking increase of monotypic cells expressing the same light chain as the M component was observed in bone marrow from 18/38 (47%) patients. A two-colour analysis clarified that the majority of myeloma cells co-expressed plasma cell and B lymphocyte markers (cyIg, CD38, CD56 and sIg), and were regarded as early-plasma cells (early-PC). In the remaining patients, myeloma cells expressed plasma cell markers only (late-PC). Phenotype corresponded to a distinct morphological pattern: early-PC showed a lympho-plasmocytoid feature with significantly lower diameters than late-PC (12.1 v 14.8 microns, P < 0.007). Moreover, the plasma cell labelling index was significantly increased in early-PC patients (1.2 v 0.5%, P < 0.04). In peripheral blood from patients with early-PC, monotypic cells co-expressing sIg and CD38, CD56, but not CD19, were also detected. These data suggest a recirculation of early-PC. Myeloma cells maintained their phenotypic pattern during the course of the disease. This observation suggests that the degree of maturation is an intrinsic characteristic of the myeloma cell population in individual patients. The evaluation of prognostic factors, such as beta 2-microglobulin, C-reactive protein and neopterin, showed a statistically significant increase in the early-PC patients, suggesting a poor outcome. In conclusion, myeloma cell phenotype allows identification of a myeloma variant with aggressive biological and clinical characteristics.

Adult↗

PubMed1991

Increased serum neopterin concentration as indicator of disease severity and poor survival in multiple myeloma.

In this study we investigated serum neopterin levels in 73 multiple myeloma (MM) patients (63 determinations at diagnosis, 58 in remission, and 35 at relapse), in 56 monoclonal gammopathies of undetermined significance (MGUS), and in 70 normal controls. Median neopterin level was 5.3 nmol/l in normal controls, 6.8 nmol/l in MGUS, and 10.7 nmol/l in MM patients. In comparison to healthy subjects, significantly higher levels were observed in MM patients (p less than 0.0001). A statistical difference was observed between MGUS and MM patients at diagnosis (p less than 0.007). Compared to diagnosis, a further increase was noticed during relapse, suggesting a correlation between neopterin and disease activity. The prognostic significance of raised neopterin levels was confirmed by a survival analysis. Median survival for patients with high values was 20 months, whereas it was 63.9 months for those with low values (log-rank test p less than 0.003). Serum neopterin concentrations also correlated to beta 2 microglobulin levels and the percentage of CD38+ circulating lymphocytes, indicating a link between neopterin and other myeloma prognostic factors.

Biomarkers, Tumor↗

PubMed1990

[Tag 72: a new tumor-associated antigen identified by a monoclonal antibody].

In order to evaluate the usefulness of Tag 72--tumor associated antigen assay--in gastroenterology, we have studied with Ca 72-4 radioimmunoassay (Centocor) 551 patients suffering benign (233) and neoplastic (318) gastrointestinal diseases and 205 normal controls. The cut-off point was fixed at 6 U/ml. Only in gastric cancers, the Tag 72 assay, with the proposed method, provide additional information in this pathology (sensitivity 30%, specificity 98.7%). The most striking observation to be made from the current study is a poor sensitivity of the test for gastrointestinal cancers, but rather the excellent specificity of the Ca 72-4 IRMA with respect to benign gastrointestinal diseases. The sensitivity of Ca 72-4 assay, vs Ca 19-9 and CEA, for the same diseases, is less, but specificity is better.

Antibodies, Monoclonal↗

PubMed1989

Paraproteinaemias and platelet aggregation: role of whole blood aggregometry.

Whole blood and optical platelet aggregation were measured in normals and in patients with paraproteinaemias; extent of aggregation was correlated with paraprotein concentrations in patients and in normals after addition of different doses of paraproteins; threshold aggregating concentrations of several agonists were also determined in whole blood and in PRP from both groups of subjects. The results indicate that patients with macromolecular monoclonal component bear a "hyperaggregable" state which can be probably ascribed also to plasma hyperviscosity and which is better detected with the impedance aggregometer.

Adenosine Diphosphate↗

PubMed1983