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Biomedical subjects

G Viale

Publications and source records attributed to G Viale.

At least 181 records · Page 10Linked to original sources

[Acute hepatic failure and renal damage. Experimental and clinical studies].

Renal damage in acute hepatic failure induced in the pig by means of an hepatic state, temporary or permanent devascularisation Amanita phalloides poisoning or orthotopic liver transplant proved of slight degree, particularly in animals treated with replacement therapy. In the cases of animals that died in acute hepatic coma, on the other hand, renal cortex ischaemia and marked medullary congestion were constant. Histologically, the damage consisted of slight tubular nephrosis; this was more apparent in the proximal tubules. Evaluation of renal damage in 38 patients with acute hepatic failure was more complicated owing to the variety of clinical conditions (level of coma, hypovolaemia, intensive care and hepatic assistance). Nevertheless, a clear relation was established between the degree of liver damage and blood creatinine and creatinine clearance values. All patients who died presented liver cell necrosis of over 75%, blood creatinine values of more than 2 mg/100 ml, and less than 50 ml/min clearance. Tubular nephrosis was the predominant lesion. It appeared that renal damage was primarily pre-renal. No signs of a true hepatorenal syndrome could be made out.

Animals↗

Membrane Ig on human lymphocytes: rate of turnover of IgD and IgM on the surface of human tonsil cells.

The turnover of IgM and IgD molecules present on the membrane of human tonsil cells has been studied using immunofluorescence and peroxidase-catalyzed membrane radioiodination. With the first of the two techniques cells were treated with pronase to remove membrane immunoglobulin (mIg), placed in culture and stained at intervals to check the reappearance of membrane IgD and IgM on the cell membrane. These experiments showed that membrane IgD (in contrast to membrane IgM) are extremely susceptible to proteolysis. Furthermore, cells treated with a concentration of pronase found to be optimal to remove membrane IgM failed to re-express membrane IgD in vitro. The large majority of tonsil lymphocytes has both membrane IgM and IgD. Due to the different behavior of reappearance of the two membrane molecules after treatment with pronase, it was not possible to obtain the simultaneous re-expression of membrane IgM and IgD by the cells "stripped" with pronase. However, the two molecules were re-expressed in vitro by the cells treated with different pronase concentrations with a similar timing, i.e. 50% or more of the cells re-expressed membrane IgD and IgM after 8 h in culture. 131I-radioiodinated membrane IgD and IgM were also released from the cell surface with a similar timing, the half-life of permanence on the cell membrane being about 4 h for both molecules. These findings thus indicate that IgM and IgD molecules have a similar turnover and that a cell is capable of placing two different Ig molecules at a time on its surface.

Cells, Cultured↗

A study of immunoglobulin classes present on the membrane and in the cytoplasm of human tonsil plasma cells.

The problem of whether immunoglobulin (Ig)-containing plasma cells expressed membrane Ig has been investigated using cells from human tonsils. In tonsils, IgG-containing cells are predominant, but a certain number of IgM, IgA and IgD-containing cells are also present. By using a double staining immunofluorescent technique for the simultaneous detection of membrane and intracytoplasmic Ig, it has been possible to ascertain that the large majority of IgA, IgM and IgD-containing cells had membrane immunoglobulin (mIg) of a class coincident with that of intracytoplasmic Ig. In addition a noticeable proportion of IgM-containing cells expressed membrane IgD, thus indicating that a certain number of these cells bore both membrane IgM and IgD. About 60% of IgG-containing cells had membrane IgG, while the remaining cells did not express mIg. Furthermore the surface staining of these cells was generally fainter than that of the cells containing other Ig classes. Experiments on the surface light chain type expressed by the single Ig-containing cells (IgCC) as compared to that found in the cytoplasm have shown that in the large majority of IgCC the light chain type of mIg coincided with that of intracytoplasmic Ig. Discordant light chain types of membrane and cytoplasmic Ig were found on about 12% of IgCC only. These values can be taken as a measure of how many IgCC had passively acquired mIg.

Cytoplasm↗

Comparative study of membrane and intracytoplasmic immunoglobulin classes in human lymphoid cells.

Immunofluorescent and "in vitro" biosynthetic techniques have been used to study the connections between the maturation process of human lymphocytes that leads to the appearance of actively secreting cells and a possible switchover from IgD to IgM production, both in homogeneous CLL cell populations and in heterogeneous cell suspensions from tonsils. The results obtained are compatible with the hypothesis that the switchover from IgD to IgM productions can be a clonal maturation phenomenon.

Antibody-Producing Cells↗

Lymphocyte membrane receptors in human lymphoid leukemias.

Membrane-bound immunoglobulins, receptors for the Fc fragment of IgG and receptors for the third component of human or murine complement were used as B cell membrane markers to study peripheral blood lymphocytes from twenty-two patients with chronic lymphatic leukemia (CLL), five patients with acute lymphoblastic leukemia (ALL) and one patient with Sézary syndrome. The capacity of human T cells of forming "spontaneous rosettes" with sheep erythrocytes was employed as T cell membrane marker. In nineteen out of twenty-seven CLL or ALL cases tested a larger percentage of cells than that found in normal individuals expressed at least one of the three B cell membrane markers studied. In the patient with Sézary syndrome the percentage of cells forming "spontaneous rosettes" with sheep erythrocytes was larger than the normal, while cells bearing B cells markers were below the normal values.

Binding Sites↗

Interleukin-13 regulates the phenotype and function of human monocytes.

The monocyte glycosylphosphatidylinositol (GPI)-linked protein CD14 serves as the receptor for lipopolysaccharide (LPS), and regulates monocyte-lymphocyte interactions. We investigated whether CD14 expression is regulated by interleukin (IL)-13, a member of the chromosome 5 cytokine family. IL-13 inhibited CD14 expression on human monocytes. CD14 down-regulation resulted in the inhibition of LPS-induced release of tumor necrosis factor alpha, and involved neither shedding nor activation of endogenous GPI-anchor-cleaving enzymes. The CD14/actin RNA ratio was decreased 7-fold in IL-13-treated monocytes. Our results suggest that IL-13 down-regulates CD14 by suppressing CD14 RNA expression. Down-regulation of CD14, the LPS receptor, may play a major role in the anti-inflammatory effects of IL-13.

Antibodies, Monoclonal↗

Calretinin. A selective marker of normal and neoplastic mesothelial cells in serous effusions.

OBJECTIVE: To document that a polyclonal antiserum to calretinin, a 29-kd calcium-binding protein, consistently decorates normal and tumor mesothelial cells in cytologic preparations. STUDY DESIGN: Thirty-three archival cytologic specimens from eight patients with histologically confirmed malignant mesothelioma and 13 from patients with metastatic serous effusions were destained and then immunostained with anticalretinin antiserum. For investigation of cell suspensions, four pleural fluids were incubated with anticalretinin antiserum. After cytocentrifugation the specimens were stained in accordance with the alkaline phosphatase anti-alkaline phosphatase (APAAP) method. For electron microscopic examination the cell suspensions were then incubated with gold-labeled antirabbit antibody. RESULTS: The diagnostic sensitivity of this new immunocytochemical approach reached 100% for the eight malignant mesotheliomas investigated. Only 3 of the 13 adenocarcinomas metastatic to the serous membranes included in this study were weakly reactive, accounting for 81% specificity. Binding of anticalretinin antiserum to living mesothelial cells was consistently documented in all four cases investigated. CONCLUSION: Calretinin is a very useful marker for positive identification of normal and tumor mesothelial cells in serous effusions.

Adenocarcinoma↗

Coexpression of intermediate filaments in normal and neoplastic human tissues: a reappraisal.

The current view that coexpression of intermediate filaments (IFs) must be considered a bizarre and unpredictable phenomenon, which seriously jeopardizes the use of their localization in diagnostic applications, is critically reviewed in light of the evidence so far acquired by investigations in vivo and in vitro. A less dogmatic approach, which considers IF expression the result of a series of interactions between cells and their microenvironment instead of a function of their histogenesis, not only justifies the complex variety of coexpressions observed in normal and neoplastic tissues but also confirms the usefulness of IF expression in diagnostic applications and offers new opportunities for investigations, with special regard to immunoelectron microscopy.

Cytoskeleton↗

Chemotherapy with vinorelbine, cisplatin and continuous infusion of 5-fluorouracil in locally advanced breast cancer: a promising low-toxic regimen.

Primary chemotherapy for locally advanced breast cancer, usually an anthracycline-containing regimen, improves local disease control allowing for an initially inoperable tumour to be resected. The feasibility and efficacy of a regimen containing vinorelbine (V), cisplatin (P) and 5-fluorouracil (5-Fu) as continuous infusion (ViFuP regimen) for patients with locally advanced breast cancer were evaluated. Twenty-six patients with a T4 breast cancer presentation (eight also had synchronous distant metastases) were treated with V (20 mg total dose i.v. on day 1 and day 3), P (60 mg/m2 i.v. on day 1) and 5-Fu (200 mg/m2/d as continuous infusion) all given every 3 weeks for a maximum of 6 courses. Eleven patients had an inflammatory breast lesion, 4 had a T4a and 11 a T4b presentation. Among those with metastases, 6 had one site and 2 had two sites of disease. After chemotherapy all tumors except one became operable. Objective response was observed in 19 out of the 26 evaluable patients (73%; 95% CI: 52-88%): fourteen had a partial response (54%); 5 had a clinically complete response (19%) and 5 had complete pathological response (20%; 95% CI: 7-41%). Seven patients had stable disease (27%) while no disease progression under treatment occurred. Mild or moderate side-effects included neutropenia (G1-G2 in 58% and G3 in 31% of patients), anemia (G1 in 19%), nausea and/or vomiting (G1-G2 in 92% of patients), mucositis (G1-G2 in 23%), diarrhea (G1 in 19%), plantar-palmar erythema (G1 in 12%) and alopecia G1 in 27% of patients. We conclude that the ViFuP regimen is well-tolerated and its use results in a high response rate. Thus ViFuP may be considered a relevant alternative to more toxic regimens, with an acceptable response rate. Despite the lack of a formal demonstration of equal efficacy with more toxic regimens commonly applied in locally advanced breast cancer, testing new modalities or drugs might provide a more fruitful strategy for relevant therapeutic progress.

Adult↗

Radiolocalization of 99mTc-labeled fragments in a melanoma xenografted model.

A xenograft model of human malignant melanoma was used to compare, in terms of tumor localization, the specific antimelanoma monoclonal antibody (MoAb) 225.28S with an irrelevant antibody (4C4). Both specific and non-specific 99mTc-labeled fragments were injected in 12 nude mice bearing subcutaneous tumor. The animals were then sacrificed at 6 and 24 hours post-injection and immediately dissected. Radioactivity of the tumor and normal tissues was measured in a well scintillation counter and autoradiography of tumor, liver and kidneys was also obtained. Tumor localization of 99mTc-labeled MoAb 225.28S fragments was highly specific compared with 99mTc-labeled irrelevant antibody 4C4. With the exception of the kidneys, already at six hours there was a satisfactory tumor-to-normal tissue ratio, which improved at 24 hours. However, the percentage of injected dose per gram of tumor decreased with time, probably due to the weaker bond of radiolabeled Fab' fragments to tumor cells. These results would indicate 99mTc-fragments of the antimelanoma MoAb 225.28S as a suitable radiotracer in clinical nuclear medicine.

Animals↗