Showing papers by "University of Turin published in 1985"

Lipid peroxidation in ethanol poisoning: a critical reconsideration.

Abstract: Evidence for the existence of increased lipid peroxidation in the liver after ethanol administration to rats is discussed. A criticism of the methods used to measure lipid peroxidation is also given. Most authors who are in favour of the presence of lipid peroxidation after ethanol have used the detection of thiobarbituric acid (TBA)-reacting substances as a measure of lipid peroxidation. This test is not entirely satisfactory, because: (1) it is not specific; (2) it mostly measures malonaldehyde, a substance of low toxicity, following a 1-2 hr incubation time; (3) several aldehydes produced during lipid peroxidation do not react with TBA. However, it is now clear that the aldehydes produced during lipid peroxidation are actively metabolized by homogenates, so differences in catabolism may influence the result of a TBA test. Measurement of the diene conjugation band, the other test usually used to detect lipid peroxidation, produces information only on the presence of dienes at a given moment, but does not give any information on the production or decomposition rates of such dienes. Thus differences in production or decomposition kinetics may mask the results. Notwithstanding these criticisms, most of the evidence at present is in favour of some involvement of lipid peroxidation in ethanol intoxication. One hypothesis is that of the direct impact of ethanol-derived free radicals. Another is that ethanol provokes the formation of oxygen free radical species, which can start lipid peroxidation either directly, or by exhausting anti-oxidant substances in the cell so as to change the balance in favour of increased peroxidation. Finally, a third hypothesis is that acetaldehyde, the main product of ethanol oxidation, is able to stimulate lipid peroxidation, possibly through the formation of free radicals, or depletion of levels of antioxidant substances. Experiments consisting of measuring total glutathione (GSH and GSSG) during lipid peroxidation stimulated by ethanol or acetaldehyde show, however, that GSH is totally converted into GSSG during the incubation, thus suggesting that the antioxidant trapped by acetaldehyde is not GSH. In isolated hepatocytes, disulfiram, an inhibitor of aldehyde dehydrogenase, does not prevent the GSH decrease caused by acetaldehyde, but can block the induced lipid peroxidation. The relevance of increased lipid peroxidation to the mechanism of the liver damage induced by ethanol remains unclear.

Identification of malignant plasma cell precursors in the bone marrow of multiple myeloma.

Abstract: Precursors of plasma cells were studied in the bone marrow of 28 patients with multiple myeloma, plasma cell leukemia, and benign monoclonal gammopathy. Pre-B and B cell populations were analyzed with anti-B monoclonal antibodies corresponding to the clusters standardized at the Leucocyte Typing Workshops in Paris and Boston (CD9, CD10, CD19-22, CD24). In advanced forms of plasma cell malignancies, such as cases of multiple myeloma in stages II and III and of plasma cell leukemia, some cells of lymphoid morphology expressed common acute lymphoblastic leukemia antigen (CALLA, CD10) and HLA-DR, but contained no detectable terminal deoxynucleotidyl transferase enzyme. These CALLA+ cells were absent in benign monoclonal gammopathies. In multiple myeloma, the CALLA+ cells were negative for surface and cytoplasmic immunoglobulins (Ig), and, unlike CALLA+, terminal deoxynucleotidyl transferase (TdT+) pre-B cells in the normal bone marrow also failed to react with antibodies to B cell-associated antigens such as CD9, CD19, CD22, and CD24. The CALLA+, Ig- cells could be regarded as preplasmacytic since, after having been separated and stimulated with the phorbol ester 12-0-tetradecanoyl-phorbol-13 acetate in vitro, they transformed into plasma cells and synthesized the same heavy and light chains as myeloma cells.

Lymphokine-activated tumor inhibition in vivo. I. The local administration of interleukin 2 triggers nonreactive lymphocytes from tumor-bearing mice to inhibit tumor growth.

Abstract: CE-2 is a chemically induced tumor of low immunogenicity in syngeneic BALB/c mice. Nylon wool columns eluting lymphocytes from the spleen of mice bearing clinically evident (5-mm mean diameter) CE-2 tumors (CE-2 TB lymphocytes) do not react with CE-2 cells in vitro, nor are they able to affect their growth in vivo in a Winn-type neutralization assay at 5:1 lymphocyte:tumor cell ratio. However, they become able to inhibit CE-2 tumor growth when 20 U of interleukin 2 (IL 2) in 0.4 ml are injected daily for 10 days at the challenge site. In contrast, mice injected with CE-2 cells and IL 2 only display tumor takes and growth that are not significantly different from those in controls challenged with CE-2 cells alone. This lymphokine-activated tumor inhibition (LATI) is not a peculiarity of the CE-2 tumor-host combination, because different tumors can be inhibited in this way and various TB lymphocytes can initiate it. In these experiments, IL 2-rich 25,000 to 30,000 m.w. fractions were obtained routinely from the culture supernatants of a clone of EL-4 thymoma stimulated with phorbol myristic acetate. Equally active IL 2-rich preparations were obtained from rat spleen cells stimulated with concanavalin A, or from MLA 144 gibbon lymphosarcoma spontaneously releasing IL 2. Treatment of CE-2 TB lymphocytes with various antibody and C, with 2000 rad gamma-irradiation, or fractionation on Percoll density gradients suggested that radioresistant functions of Thy-1.2+, Lyt-1.2+, Lyt-2.2- and of asialo GM1+ cells are independently involved in LATI induction. These lymphocytes inhibit tumor growth by recruiting the radiosensitive effector mechanisms of the recipient mice required for ultimate tumor destruction. CE-2 tumor inhibition by LATI leaves a specific delayed-type hypersensitivity and an immunologic memory, resulting in rejection of a second lethal CE-2 challenge in a significant number of mice.

Occupation and bladder cancer in males: a case-control study.

Abstract: A case-control study of 512 male cases of bladder cancer and 596 male hospital controls (all living in the province of Turin, Northern Italy, an area with a high proportion of car workers) has been analyzed for occupations. Relative risks were 1.8 (95% c.1. 0.9–3.6) for the textile industry, 3.8 (1.3–11.5) for the leather industry, 1.8 (0.8–4.0) for printing, 8.8 (2.7–28.6) for dyestuff production, 1.2 (0.6–2.4) for tire production and 2.5 (1.0–6.0) for other rubber goods, 2.0 (0.9–4.5) for brickyards and related activities. A relative risk of 3.1 (0.9–10.5) was found for turners having started work before 1940 and with at least 10 years of activity. For truck drivers the relative risk was 1.2 (0.6–2.5). A job-exposure matrix was developed for the development of new hypotheses; an association with bladder cancer was found for aromatic amines only. The attributable risk percent in the population was estimated as 10%, when only those occupations consistently associated with bladder cancer were considered.

Chromogranin-reactive endocrine cells in argyrophilic carcinomas ("carcinoids") and normal tissue of the breast.

Abstract: Breast carcinomas, either positive or negative with the Grimelius' silver procedure, benign fibroadenomas, duct papillomas, and areas of histologically normal breast tissue were tested immunocytochemically with the mouse monoclonal antibody LK2H10 directed against human chromogranin. This is regarded as a general stain for polypeptide-hormone-producing cells and tumors. In 3 of the 9 cases of argyrophilic carcinoma, but in none of 12 ductal infiltrating carcinomas, chromogranin-positive cells were found: the number of reactive cells was very low in 1 case, while in the other 2 carcinomas about 50% of the argyrophilic cells appeared stained. In areas of histologically normal breast tissue, rare argyrophilic chromogranin-positive cells were detected. This study is the first reported evidence concerning the presence of endocrinelike cells probably belonging to the diffuse neuroendocrine system in the normal mammary parenchyma. Our data are consistent with the endocrine nature of at least some of the breast argyrophilic carcinomas.

Inhibition of interferon-gamma may suppress allograft reactivity by T lymphocytes in vitro and in vivo.

Abstract: The addition to mixed-leukocyte reactions of monoclonal antibodies to interferon-gamma abrogated alloantigen recognition and induction of cytotoxic T lymphocytes by inducing early and highly effective suppressor T lymphocytes. This inhibitory activity was not confined to in vitro models, since daily injection of the antibodies into CBA/J mice blocked the usual rejection of allogenic tumor cells.

Genetic and population structure of four Sardinian villages.

Abstract: Data on microgeographic population structure on four neighbouring villages of Sardinia island (Italy) are presented and discussed. Two villages are located in the lowlands where malaria from Plasmodium falciparum was endemic until the eradication of paludism. The other two villages are located in the highlands and they were malaria-free because of the altitude. Census data, inbreeding, migration matrices and surname distributions have been collected. The genetic differentiation of the four villages, tested for 31 genetic polymorphisms (106 alleles), is only in part compatible with migration rates inferred from demographic data. The possible adaptive nature of some genetic markers with respect to malarial resistance is discussed. Ambiguous results from population genetics quantitative methods do not support definite answers.

Immunohistological evidences of cortical and medullary differentiation in thymoma

Abstract: The phenotypical characteristics of human epithelial and lymphoid cells have been studied with immunohistochemical methods on frozen sections of 12 thymomas. On the basis of the cytohistological characteristics of thymoma epithelial cells (EC) the thymomas were divided in cortical, medullary and mixed types, according to recently developed light microscopical criteria. When tested with a series of monoclonal antibodies, thymoma EC were all stained by the antibody Ki-M3 (as in the thymus), but reacted with anti-HLA-DR, anti-HLA-A,B,C and with a new monoclonal antibody to cortical EC, 21A6, to a lesser extent and with weaker, variable intensity in comparison with the normal thymus. Cortical type thymomas were most reactive and the medullary type almost negative. Thymomas, like normal thymus showed different immunoreactivity patterns with antibodies to prekeratins of different specificities. Cortical type thymomas and areas in mixed thymoma showed an EC staining with the antibody to non-squamous type keratin (35 beta H11) whereas medullary type thymomas and areas showed staining with antibodies to squamous-type keratin (34 beta E12-IV/82) in addition. Lymphoid cells with cortical (OKT6+, Leu 1 weakly+, Leu 2a+, Leu 3a+) or mature medullary (OKT6-, Leu 1 strongly+, Leu 2a or Leu 3a+) phenotype were found to colonize tumours with different EC types. These immunohistochemical findings largely confirm our earlier cytological distinction of thymoma EC. In addition important differences have been observed in neoplastic cortical EC concerning the HLA-DR and 21A6 immunoreactivity that may be intimately related to the neoplastic process and paraneoplastic immune phenomena.

Immunohistochemical demonstration of follicular dendritic cells in bone marrow involvement of B-cell chronic lymphocytic leukemia.

Abstract: Using a sensitive immunohistochemical technique and a specific monoclonal antibody (RFD-3), follicular dendritic cells (FDC) have been demonstrated in a significant proportion (6/12) of bone marrow samples from patients with nodular marrow involvement of B-cell chronic lymphocytic leukemia (B-CLL). In all cases with "packed marrow" involvement and advanced stages of disease the FDC were absent. As these accessory cells are normally present only in the lymph nodes, their presence in the bone marrow is in accord with the view that B-CLL might be the malignancy of an immature subpopulation of lymph node lymphocytes that invade the bone marrow.

Evidence combination in expert systems

Abstract: This paper discusses some of the problems related to the representation of uncertain knowledge and to the combination of evidence degrees in rule-based expert systems. Some of the methods proposed in the literature are briefly analysed with particular attention to the Subjective Bayesian Probability (used in PROSPECTOR) and the Confirmation Theory adopted in MYCIN. The paper presents an integrated approach based on Possibility Theory for evaluating the degree of match between the set of conditions occurring in the antecedent of a production rule and the input data, for combining the evidence degree of a fact with the strength of implication of a rule and for combining evidence degrees coming from different pieces of knowledge. The semantics of the logical operators AND and OR in possibility theory and in our approach are compared. Finally, the definitions of some quantifiers like AT LEAST n, AT MOST n, EXACTLY n are introduced.

Morphological parameters in lupus nephritis: their relevance for classification and relationship with clinical and histological findings and outcome.

Abstract: One hundred and sixty-seven renal biopsies from 147 patients with lupus nephritis were studied retrospectively to assess the contribution to morphological classification by features assessed with immunofluorescence and electron microscopy, together with pathological indices obtained by scoring specific histologic changes. The prognostic relevance of the histologic scoring was also evaluated. The biopsies were assigned to the following classes: I, absence of glomerular lesions; II, mesangial proliferation; III, focal segmental proliferation; IVa, diffuse (more than 50 per cent of the glomeruli) but segmentally distributed proliferation; IVb, diffuse and generalised proliferation; IVc, extracapillary proliferation; Va, pure membranous changes; Vb, membranous changes with slight mesangial proliferation; VI, association of class V and class III or IV. The incidence and degree of some glomerular and non-glomerular 'active' and 'sclerotic' changes as assessed by light microscopy were evaluated in the different classes. Both the activity and sclerosis indices obtained by scoring these lesions were found to be significantly higher in classes with glomerular proliferative changes. Eighteen patients had a second biopsy and two of these had a third; more severe changes were observed in nine and improvement in four. In 146 biopsies light microscopy findings were compared with immunofluorescence patterns (negative, mesangial, mesangial and peripheral, peripheral, membranous). The mesangial pattern was mainly present in class II with a few examples in classes I and III; in the last two the mesangial-peripheral pattern was most common; the peripheral pattern was by far the most common in class IV (a, b and c) and frequent in class VI; a membranous pattern was the rule in class V and occasionally found in class VI. Immunoglobulins (Igs) and complement (C) fractions were simultaneously present in most cases, IgG, C3 and C1q being the commonest in all classes. Except for IgM and fibrinogen, the differences in distribution of Igs and C fractions among the various classes were statistically significant. The deposits most commonly found by electron microscopy in all biopsies were mesangial; subendothelial deposits were mainly found in classes with active glomerular changes, frequently associated with deposits at the other sites in the most severe cases. A highly significant correlation was found between the activity index and the sclerosis index and severity of the clinical picture at biopsy. An unfavourable progress was confined mainly to classes with extensive intracapillary proliferation and correlated significantly with the highest activity and sclerosis indices.(ABSTRACT TRUNCATED AT 400 WORDS)

Alkyl-ether phosphoglycerides influence calcium fluxes into human endothelial cells.

Abstract: Suspended or adherent human endothelial cells (HEC) treated with 5 to 100 nM 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC, platelet-activating factor) showed a marked concentration and temperature-dependent increase in calcium uptake. This effect was also elicited by some AGEPC analogs. At 10 nM, the relative potencies were AGEPC = 100; 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphoric acid (AGEPA) = 52.9; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphoethanolamine (AGEPE) = 20; 1-O-octadecyl-2-deoxy-2-acetamido-sn-glycero-3-phosphocholine (2-acetamido-analog)-inactive at 100 nM = 25; 1-octadecyl-2-methoxy-sn-glycero-3-phosphocholine(2-methoxy analog)-inactive, and at 100 nM = 50. 1-O-octadecyl-2-lyso-sn-glycero-3-phosphocholine(lyso-GEPC) (100 nM) was inactive. The increase in calcium uptake was accompanied by a rise in membrane-associated calcium. The ratio between nonmembrane-bound intracellular calcium and membrane-associated calcium was constant for all agonists. CV-3988, a specific AGEPC antagonist, inhibited the effect of AGEPC. Preexposure of adherent HEC to AGEPC inhibited calcium uptake upon subsequent stimulation, suggesting a deactivation of the putative receptor. AGEPC (5 to 100 nM), but not lyso-GEPC, also stimulated calcium-efflux from calcium-preloaded, adherent HEC. AGEPC and 2-acetamido-analog, at concentrations able to induce calcium influx, did not elicit the production of 6-keto-PGF1 alpha.

Cystic hygroma: Prenatal diagnosis and genetic counselling

Abstract: Six cases of cystic hygromas detected during second trimester ultrasound examination are reported: 4 fetuses (67 per cent) had a 45, X karyotype, 1 fetus had trisomy 18, 1 fetus had a normal karyotype (46,XX) and at autopsy multiple anomalies were observed. In the latter case the family history suggested an autosomal recessive pattern of inheritance. In order to reach a definite diagnosis and give proper genetic counselling when a fetus is found to have cystic hygroma, a fetal karyotype as well as a family and reproductive history should be obtained.

Detection of HBV-DNA by in situ hybridization using a biotin-labeled probe.

Abstract: A biotin-labeled DNA probe specific for hepatitis B virus (HBV) nucleotide sequences was hybridized in situ to liver tissue of 20 patients; 16 were chronic carriers of hepatitis B surface antigen (HBsAg) and 4 had no markers of HBV infection. HBV-DNA was also analyzed in the serum and the liver of these patients by spot and Southern blot hybridization, respectively. Liver specimens from six carriers were positive for HBV-DNA both by in situ and Southem blot hybridization; ten carriers were negative by in situ hybridiza- tion, and two of these were positive by Southern blot technique. The staining was granular, mainly cytoplasmic, limited to liver specimens containing replicative forms of HBV-DNA, and associated with detection of HBcAg in hepatocytes by immunofluorescence. The sensitivity of this technique was not sufficient to detect few copies of integrated HBV-DNA. The hybridization procedure was specific, as results were constantly negative in liver specimens of patients without markers of HBV infection, and no reaction was observed using DNA probes lacking HBV-DNA sequences. Detection of HBV-DNA by in situ hybridization, using a biotinylated probe, is a rapid, reproducible, and specific histochemical method. Currently available biotinylated probes are advantageous when absolute sensitivity is not the limiting factor, and they also facilitate studies of the cellular and subcellar distribution of HBV nucleic acids.

Initial phase of chromospheric evaporation in a solar flare

Abstract: Attention is given to the initial phase of chromospheric evaporation in the solar flare observed by the Solar Maximum Mission's Hard X-ray Imaging Spectrometer, on May 21, 1980. Images of the flaring region in the 3.5-8.0 and 16-30 keV energy bands indicate that both the soft and hard X-ray emissions are localized near the footpoints early in the event, while they are weaker from the rest of the flaring loop system; this implies that there is no heating taking place at the top of the loops, while energy is primarily deposited at their base. Observations of the energy deposition in the chromosphere by electrons accelerated in the flare region to energies above 25 keV furnish further support for an interpretation of plasma upflows as the mechanism responsible for the formation of the soft X-ray flare, identified with chromospheric evaporation.