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Biomedical subjects

E Ferrero

Publications and source records attributed to E Ferrero.

At least 55 records · Page 3Linked to original sources

Pathologic changes, tissue distribution, and extent of conversion to ethylenethiourea after subacute administration of zinc ethylene-bis-dithiocarbamate (zineb) to calves with immature rumen function.

The toxicity of zinc ethylene-bis-dithiocarbamate (zineb), a widely used fungicide, was studied in four 4-week-old Friesian calves with immature rumen function. Calves were first subjected to liver biopsy, and thereafter, 3 of them were orally administered 200 mg of zineb/kg of body weight daily for 80 days, whereas the fourth calf served as control and remained untreated. Clinical, hematologic, and pathologic (including ultrastructural) findings were recorded. The distribution in body fluids and tissues of the parent compound and one of its main metabolites, ethylenethiourea (ETU), also was examined. Treated calves had unthrifty appearance and reduction in weight gain. They also had remarkable impairment of thyroid function, as reflected by reduction in serum concentrations of triiodothyronine and thyroxine and increase in weight of the thyroid gland associated with epithelial vacuolization and foci of hyperplasia. Moderate increase in liver glycogen content and impairment in maturation of germ cells were recorded consistently. Whereas zineb was widely distributed in body tissues, ETU accumulated mainly in the liver and the thyroid gland, although noticeable concentrations also were attained in muscle. Data were consistent with involvement of ETU mainly in the pathogenesis of thyroid gland lesions, and indicate that unweaned calves given zineb develop a clinicopathologic syndrome that does not differ qualitatively from that already described in adult cattle exposed to zineb.

Age Factors↗

CD14 is a member of the family of leucine-rich proteins and is encoded by a gene syntenic with multiple receptor genes.

We have isolated and characterized genomic and cDNA clones encoding the murine homolog of the human monocyte/granulocyte cell surface glycoprotein, CD14. As in man, the expression of murine CD14 is limited to the myeloid lineage. The murine and human CD14 genes are highly conserved in their intron-exon organization and nucleotide sequence. Their deduced protein sequences show 66% amino acid identity. In both mouse and man, the CD14 protein contains a repeating (10 times) leucine-rich motif (LXXLXLX) that is also found in a group of heterogeneous proteins from phylogenetically distant species. The CD14 gene has been mapped to mouse chromosome 18 which also contains at least five genes encoding receptors (Pdgfr, Adrb2r, li, Grl-1, Fms). Thus CD14 and the receptor genes form a conserved syntenic group localized on mouse chromosome 18 and human chromosome 5. The inclusion of CD14 in the family of leucine-rich proteins, its expression profile and the murine chromosomal localization support the hypothesis that CD14 may function as a receptor.

Amino Acid Sequence↗

Recombinant interleukin-2 and lymphokine-activated killer cells in renal cancer patients: I. Phenotypic and functional analysis of the peripheral blood mononuclear cells.

The efficacy of recombinant interleukin-2 (rIL-2) or rIL-2 plus lymphokine-activated killer (LAK) cells in cancer therapy has been demonstrated by several groups both in experimental models in animals and clinical trials in humans, but their effects in vivo have yet to be clarified. Starting February 1988, we have treated 12 patients affected by advanced renal cancer with rIL-2 + LAK cells according to an open, non-randomized, phase II trial. Immediately before each rIL-2 infusion and during the last day of infusion, immunological tests were performed on the patients' peripheral blood mononuclear cells. During rIL-2 infusion we have observed a slight increase of the spontaneous cell proliferation and of natural killer (NK) and LAK activity; phenotypic analysis showed a significant decrease in the CD4+ T-lymphocyte subset, both in percentage and in absolute number. Conversely, before each cycle CD4+ cells increased when compared to basal values. No significant variations were observed in the CD8+ T-lymphocyte subset. Furthermore, a significant increase of the NK cells (CD3- CD56+ CD16+) was evident during rIL-2 infusion.

CD4 Antigens↗

LAK1 antigen defines two distinct subsets among human tumour infiltrating lymphocytes.

Both lymphokine activated killer (LAK) cells and specific cytotoxic T lymphocytes appear to play a role in tumour immunity. Tumour infiltrating lymphocytes (TIL) which display a CD56+ phenotype (both CD3+ and CD3-) are also likely to possess anti-tumour activity. We have previously described a 120 kDa surface antigen, termed LAK1, expressed on a subset of human peripheral blood lymphocytes (20-50%) with both NK and LAK activity. The aim of the present study was to determine whether LAK1 antigen is able to distinguish among TIL two populations of effector cells displaying either specific or non MHC-restricted (NK/LAK) activity. We showed that about 25% of freshly derived TIL were weakly stained with anti-LAK1 monoclonal antibody and most of them were also CD3+ CD56-. After culture in recombinant interleukin-2 the majority of TIL were CD3+ CD56- and the percentage of LAK1+ cells increased up to 50%. Among cloned TIL, only those lacking LAK1 antigen displayed a specific cytotoxicity against the autologous tumour, whereas the non-lytic clones were able to produce both tumour necrosis factor and gamma-interferon. Moreover, when TIL from a renal cell carcinoma were fractionated into LAK1- and LAK1+ populations, the specific lytic activity was mainly evident when LAK1- lymphocytes were used as effector cells. Conversely, LAK activity was confined to the LAK1+ subset.

Antigens, Differentiation, T-Lymphocyte↗

[Morphologic changes in ileoanal reservoirs 2 years after their construction].

A study was made of the histologic changes in the mucosa of the ileoanal reservoirs of 10 patients who 2 years earlier had undergone ileoanal anastomosis with a J reservoir for ulcerative colitis (CU). In biopsies of the reservoirs were evaluated: 1) basic morphologic changes; 2) morphometric differences with respect to normal ileal mucosa; 3) the immunohistochemical pattern (IHQ) (IgA, IgG, IgM and CEA) of the reservoir mucosa as compared to normal ileum, active ulcerative colitis. Crohn's disease and celiaca; 4) the possible existence of atypias or dysplasias of the reservoir mucosa; and 5) the number of argentaffin cells per field. The basic morphologic alteration consisted of colonic metaplasia. Reservoir biopsies exhibited partial (8 cases) or subtotal atrophy (2 cases) of the mucosa. With respect to the normal ileum there was a decrease in villi height (p less than 0.05), an increase in crypt depth (p less than 0.05) and a higher index of mucosal regeneration, with a larger number of cells and mitoses per crypt (p less than 0.05). Fifty percent of the reservoirs presented a chronic inflammatory pattern with an acute component in 30% of them. The immunohistochemical pattern of the reservoirs not inflamed was similar to that of normal ileum (IgA much greater than IgM greater than IgG) and that of the inflamed reservoirs was similar to that of intestinal inflammatory disease (marked increase in the IgG. CEA (similar to what?) an alteration of local immune homeostasis could have of the genesis of pictures of "pouchitis". No alarming signs of atypia or dysplasia were found, nor changes in the population of argentaffin cells.

Anal Canal↗

The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage.

CD14 is a myeloid differentiation Ag expressed primarily on peripheral blood monocytes and macrophages. Although its function is unknown, the CD14 gene maps to a region encoding several myeloid growth factors and receptors. Analysis of the CD14 protein sequence deduced from the cDNA shows that although the CD14 protein contains a characteristic leader peptide, it lacks a characteristic transmembrane region, suggesting that CD14 may be anchored to the membrane via glycosylphosphatidylinositol (PI). Treatment of monocytes as well as a CD14-expressing neuroglioma cell line with PI-phospholipase C removed CD14 from the cell surface. Furthermore, monocytes from a patient with paroxysmal nocturnal hemoglobinuria, a disease characterized by lack of expression of other PI-linked proteins, failed to express CD14. Interestingly, the CD14-expressing neuroglioma cell line, which had been transfected with a single CD14 cDNA, released a soluble form of CD14 into the supernatant. Soluble forms of CD14 have previously been observed in serum of normal individuals and in culture supernatants of CD14+ cells. Biosynthetic experiments reveal that this soluble form of CD14 (48 kDa), which is smaller than the form released from the membrane by PI-phospholipase C (53 kDa), does not contain ethanolamine, the first constitutent of the PI-anchoring system. These studies demonstrate that CD14 is a member of the family of PI-anchored proteins and suggest that soluble forms of CD14 represent molecules that completely lack the PI-anchoring system.

Amino Acid Sequence↗

The CD14 monocyte differentiation antigen maps to a region encoding growth factors and receptors.

CD14 is a myelomonocytic differentiation antigen expressed by monocytes, macrophages, and activated granulocytes and is detectable with the monoclonal antibodies MO2, MY4, and LeuM3. Analyses of complementary DNA and genomic clones of CD14 show that it has a novel structure and that it maps to chromosome 5 within a region containing other genes encoding growth factors and receptors; it may therefore represent a new receptor important for myeloid differentiation. In addition, the CD14 gene is included in the "critical" region that is frequently deleted in certain myeloid leukemias.

Animals↗

Stepwise activation of T cells. Role of the calcium ionophore A23187.

The calcium ionophore A23187, at a concentration of 1 microgram/ml, is able to stimulate proliferation of freshly isolated peripheral blood lymphocytes, CD4+-enriched cells, or CD8+-enriched cells as measured by [3H]thymidine incorporation. This proliferation is accompanied by an increase in interleukin 2 (IL-2) receptor expression but not by a detectable up-regulation in (IL-2) production or the development of cytotoxicity. Proliferation can be blocked by anti-CD3, CD4, or CD8 monoclonal antibodies, but not by anti-Tac. If CD8+-enriched cells are activated for 3 days with A23187 and the blasts present on day 3 are sorted and returned to culture, they rapidly develop cytolytic activity in the presence of recombinant IL-2 but not recombinant interferon-gamma. CD4+ enriched cells, after activation with A23187, do not become cytotoxic in the presence of either recombinant IL-2 or recombinant interferon-gamma. These findings permit study of the stepwise maturation of T cells in this alternative pathway by using "minimal signals" that do not, by themselves and as used in these studies, stimulate precursor Tc to mature to full effector cytotoxic function. These findings are consistent with the model that A23187 drives T cells only part way along a pathway of maturation and that an additional second signal must be given to effect maturation of cytotoxic status.

Antibodies, Monoclonal↗

Definition by CB12 monoclonal antibody of a differentiation marker specific for human monocytes and their bone marrow precursors.

The CB12 monoclonal antibody, which reacts with a molecule expressed on monocytes, was characterized using human embryonic material as immunizer. Analysis of the monoclonal antibody at the phenotypic, molecular, and functional levels indicates that its reactivity is restricted to circulating monocytes and their precursors in the bone marrow, whereas it is undetectable on tissue macrophages. CB12 displays a pattern of reactivity compatible with that of a marker of monocyte differentiation. Preliminary data indicate a possible receptor role for the CB12 molecule.

Antibodies, Monoclonal↗

Fc receptor triggering induces expression of surface activation antigens and release of platelet-activating factor in large granular lymphocytes.

Triggering of large granular lymphocyte (LGL) Fc receptor with a specific monoclonal antibody (AB8.28) linked to an insoluble matrix induces cell activation, as witnessed by expression of HLA class II (DR and DQ) molecules and interleukin 2 receptor. Moreover, this event is accompanied by a concomitant release of platelet-activating factor by LGL. We conclude that the Fc receptor molecule identified by mAb AB8.28 represents a trigger for LGL activation.

Antibodies, Monoclonal↗

Impairment of lymphocyte-suppressive system in recent-onset insulin-dependent diabetes mellitus. Correlation with metabolic control.

Impairment of suppressor-cell activity may be important in the pathogenesis and maintenance of insulin-dependent diabetes mellitus (IDDM). In 23 recent-onset IDDM patients, lymphocyte sensitivity in vitro to theophylline was tested both in basal conditions and after improvement of metabolic control. This pharmacologic agent is mainly effective on a lymphocytic subpopulation with phenotypic and functional suppressive features. Peripheral blood lymphocytes from IDDM patients showed a loss of theophylline sensitivity, identified as inhibition of both E-rosette formation and blastogenic response to polyclonal mitogens concanavalin A (ConA) and phytohemagglutinin (PHA). An inverse relationship was demonstrated between the theophylline-induced suppression of ConA blastogenic response and blood glucose and glycosylated hemoglobin levels (P less than .01). Metabolic control seemed to be important even in relation to lymphocyte subpopulation distribution. In IDDM patients we found a significant (P less than .05) reduction of OKT4+ lymphocytes that is correlated with blood glucose and glycosylated hemoglobin levels (P less than .01). The improvement of metabolic control led to recovery of theophylline sensitivity. We suggest a deficiency in a suppressive system that could be involved in IDDM onset and the possible role of metabolic control in the impairment of some immunologic functions reported with this pathologic condition.

Adolescent↗

Acute effect of a single infusion of papaverine on human peripheral lymphocyte.

It has been reported that drugs which modulate the intracellular levels of 3' 5' cyclic adenosinemonophosphate (cAMP) interfere with the cellular function of the immune system. In this work, papaverine, a drug effective in elevating cAMP levels, was observed to increase the T4+/T8+ ratio in vivo. Furthermore, peripheral blood mononuclear cells (PBMC) from young healthy volunteers who received intravenous papaverine (3 mg/kg i.v. over 15 min) showed a decreased response in allogenic mixed lymphocyte reaction (MLR) but a normal behaviour in a polyclonal mitogen assay and in autologous MLR (AMLR). These findings suggest that papaverine administration could influence the immune system functions.

Adult↗

In vitro effects of halothane on lymphocytes.

Many reports indicate that anaesthesia affects several immunological functions that decrease the immune response, but the mechanisms involved are still unknown. We investigated the in vitro effect of halothane on human lymphocyte metabolism and plasma membrane function by evaluating the intracellular concentration of 3',5'-cyclic adenosine-monophosphate (cAMP), phosphodiesterase enzyme activity, NAD+/NADH intralymphocytic ratios and the degree of antibody and lectine-induced 'capping' of surface markers. Our results demonstrated an impaired lymphocyte capping of surface immunoglobulins and concanavalin A receptors 60 min after exposure to halothane at the concentration of 1% in oxygen. This phenomenon was reversible after 24 h and it was unrelated to the presence of adherent cells during the culture. Furthermore, halothane was able to induce a persistent increase in cAMP intracellular concentrations, which was reversible within 48 h. This effect was not dependent on adherent cells or on phosphodiesterase enzyme inhibition. Finally, no alteration in NAD+/NADH ratios after halothane exposure was observed.

Cyclic AMP↗

Immunological characterization of the vitellogenic proteins in Squilla mantis hemolymph (Crustacea, Stomatopoda).

The femal specific proteins (FSP) identified in the hemolymph of Squilla mantis females are here proven to be vitellogenins (VTG) by immunological and electrophoretical methods. VTG 1 which has a higher molecular weight (MW) and only one central form, both in hemolymph and eggs, can be detected immunoelectrophoretically. VTG 2 and 3 have similar lower MW and are immunologically closely related, their slightly cathodic precipitation are fusing with the slightly anodic form. A further cathodic shift of the double arc occurs in the corresponding egg proteins. The VTGs are forms of yolk proteins which are transported in the hemolymph from the site of synthesis to the ovary where they undergo structural variations without involving a change of MW or of their number.

Animals↗

Effect of cyclosporine and aminophylline on streptozotocin-induced diabetes in rats.

Diabetes induced in rats by multiple low doses of streptozotocin is thought to mimic type 1 disease in man. We tested the effect of concomitant treatment with immunomodulator drugs in this diabetic experimental model. Administration of cyclosporine resulted in a rapid appearance of hyperglycemia, perhaps by a potentiation of the direct cytotoxic action of streptozotocin on beta cells. By contrast, aminophylline administration protected the animals from the diabetogenic action of streptozotocin. Concomitant treatment with aminophylline and cyclosporine failed to protect the rats from the hyperglycemia induced by streptozotocin.

Aminophylline↗