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Biomedical subjects

M Sironi

Publications and source records attributed to M Sironi.

At least 181 records · Page 10Linked to original sources
PubMed1983

Immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in strains of mice with different susceptibility to induction of aryl hydrocarbon hydroxylase.

Mouse strains with different susceptibility to aryl hydrocarbon hydroxylase (AHH) induction and with different levels and/or affinity for a specific cytosolic binding protein ("receptor") were used to investigate the immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Humoral antibody production was strongly inhibited in C57Bl/6 and C3H/HeN mice (more susceptible strains) with very low, single doses of TCDD (1.2 micrograms/kg), while other strains (DBA/2 and AKR) required higher doses (at least 6 micrograms/kg) to be partially suppressed. Longer exposure (8 weeks) did not increase the sensitivity of DBA/2 mice. A good correlation between the degree of enzyme inducibility and immunosuppression was observed in studies with B6D2F1 mice and backcrosses. Similar results were obtained with 2,3,7,8-tetrachlorodibenzofuran (TCDF), the most powerful competitor for TCDD "receptor" in vitro and in vivo. TCDD immunotoxic effects appeared to be associated with the presence of a specific cytosolic binding protein which mediates AHH induction.

Animals↗
PubMed1980

The effect of acute administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on humoral antibody production and cell-mediated activities in mice.

The effect of single doses of TCDD (1.2, 6 or 30 gamma/kg) on several immune parameters has been investigated in young adult C57B1/6 mice. TCDD profoundly suppressed the primary and secondary humoral response to T-dependent (sheep erythrocytes, SRBC) and T-independent (Type III pneumococcal polysaccharide, S III) antigens. In vitro lymphoproliferative responses to Concanavallin A (Con A) and bacterial lypopolysaccharide (LPS), and macrophage and natural killer (NK) cell-mediated cytotoxicity were not significantly affected per unit number of lymphoid cells. Moreover, the ability of splenocytes from TCDD treated animals to mediate a graft versus host (GVH) reaction was not impaired.

Animals↗
PubMed1980

Effect of acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on humoral antibody production in mice.

The effect of single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 1.2, 6 or 30 micrograms/kg i.p.) on primary humoral antibody production was studied in young adult C57 BL/6J mice. TCDD profoundly suppressed the primary response to thymus-dependent (sheep erythrocytes) and independent (type III pneumococcal polysaccharide) antigens. The inhibitory effect of TCDD was still detectable 42 days after treatment. In contrast, under these experimental conditions, in vitro lymphoproliferative responses to Concanavalin A (Con A) and bacterial lypopolysaccharides and the ability to mediate graft versus host reaction were not significantly affected per unit number of lymphoid cells.

Animals↗
PubMed1980

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on macrophage and natural killer cell-mediated cytotoxicity in mice.

C57Bl/6 J mice (6-8 weeks old) were given single i. p. doses (1, 2, 6 and 30 micrograms/kg) of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) and macrophage-mediated and natural killer (NK) cell-mediated cytotoxicity was evaluated at different times after treatment. Peritoneal macrophage cytolytic activity was measured as 3H-thymidine release from prelabelled mKSATU5 target cells in a 48 hours assay; macrophage-mediated cytostasis was assessed in terms of inhibitions of 3H-thymidine uptake by SL2 lymphoma cells. Spleen NK activity was measured using 51Cr-labelled YAC-1 lymphoma cells as targets. TCDD did not modify spontaneous macrophage-mediated and NK cell-mediated cytotoxicity per unit number of effector cells nor did it affect the macrophages' capacity to express increased cytolytic and cytostatic activity in the presence of endotoxin. Lower numbers of peritoneal macrophages and splenocytes were recovered from TCDD treated mice. Thus the total numbers of lytic units recovered from animals exposed to TCDD were lower than controls. Impairment of these cellular effector mechanisms, due to cell loss rather than inhibition of function, might play a role in the lowered resistance to bacterial infection of mice given TCDD and in the carcinogenic and cocarcinogenic activity of this chemical.

Animals↗
PubMed1978

Comparative antineoplastic activity of adriamycin and N-trifluoroacetyladriamycin-14-valerate.

A comparative investigation of the antineoplastic activity of adriamycin and its derivative, N-trifluoroacetyladriamycin-14-valerate (AD 32), was conducted in murine tumor models employing different treatment schedules and injection routes. In all conditions tested, ie, ascitic and disseminated L1210 leukemia, ascitic LSTRA lymphoma, and advanced Lewis lung carcinoma, AD 32 was significantly more effective in terms of lifespan prolongation and induction of cures than optimal adriamycin treatments. As with adriamycin, AD 32 was ineffective on ic transplanted L1210 leukemia.

Animals↗
PubMed1978

Preliminary characterization in mice of the effect of isoprinosine on the immune system.

A preliminary characterization of the immunomodulatory activity of isoprinosine in mice was conducted in both normal and tumor-bearing mice. Under the experimental conditions employed, isoprinosine given ip and orally was found to possess some immunomodulatory capacity in various model systems. The compound appeared to preferentially influence T- but not B-cell responses; it did not apparently influence the functional capacity of macrophages, K cells, and NK cells.

Animals↗
PubMedDate not supplied

Interleukin-10 inhibits lipopolysaccharide-induced tumor necrosis factor and interleukin-1 beta production in the brain without affecting the activation of the hypothalamus-pituitary-adrenal axis.

Interleukin (IL) 10 inhibits endotoxin (lipopolysaccharide; LPS) induced tumor necrosis factor (TNF) production in vivo and in vitro. In turn, IL-10 is induced by LPS and acts as a negative feedback to limit TNF production. We investigated the effects of IL-10 on brain TNF and IL-1 beta production induced by a central LPS administration in mice. Because central LPS also induces peripheral TNF, we also measured the serum TNF levels. A single intracerebroventricular injection of murine recombinant IL-10 (75 ng/mouse) simultaneously with LPS (2.5 micrograms/mouse) almost completely inhibited brain TNF production. The brain IL-1 beta production was also inhibited, as was the serum concentration of the acute-phase protein serum amyloid A. On the other hand, intracerebroventricular administration of an anti-IL-10 monoclonal antibody (JES5-2A5; 60 micrograms/mouse) potentiated brain TNF and IL-1 beta production. Identical results were obtained when the serum TNF levels were measured. IL-10 did not affect the LPS-induced increase of serum corticosterone, the main endogenous inhibitor of TNF production, or the induction of IL-6. These results indicate that LPS-induced IL-10 can act as an important endogenous inhibitor of brain TNF production and suggest an anti-inflammatory role for IL-10 in the central nervous system.

Animals↗
PubMedDate not supplied

Centrally mediated inhibition of local inflammation by ciliary neurotrophic factor.

Since ciliary neurotrophic factor (CNTF) inhibits the production of TNF and activates the hypothalamus-pituitary-adrenal axis (HPAA), we investigated whether CNTF can produce antiinflammatory actions and whether it may act through a central mechanism, using the murine air pouch model of inflammation. In this model, inflammation is evaluated by measuring the induction of TNF and IL-6 as well as cell recruitment in the pouch fluid 24 h after carrageenan. Intracerebroventricular injection, but not intravenous or local injection of CNTF markedly inhibited inflammation. This was associated with high serum corticosterone levels, and antiinflammatory action was not observed in adrenalectomized mice, indicating that an intact HPAA is required. A CNTF receptor antagonist increased carrageenan inflammation, suggesting that endogenous CNTF might have a centrally mediated antiinflammatory role.

Adrenalectomy↗
PubMedDate not supplied

Effect of phenobarbital on cyclophosphamide cytotoxic activity and pharmacokinetics in mice.

The interaction between cyclophosphamide (CPA) and phenobarbital (PB) was investigated in B6D2F1 mice, checking both the antileukemic and immunosuppressive activity together with the serum levels of CPA and its metabolites. A reduced cytotoxic activity of CPA has been observed when PB is given for 2 days before CPA and an interval of at least 6 hours elapses between the last treatment of PB and the administration of CPA. On the contrary, when PB is given simultaneously with CPA for 2 or 4 consecutive days, an increased antileukemic activity of CPA occurs. In the experimental condition where PB decreases the activity of CPA, serum levels of CPA, assayed by means of a new specific gas-chromatographic method, and of its NBP-alkylating metabolites, indicate that this effect may be explained on a pure pharmacokinetic basis. However, for the situation where an increased effect of CPA was observed under the influence of PB, pharmacokinetic data did not provide a clear explanation.

Animals↗
PubMedDate not supplied

Protective effect of n-acetylcysteine in a model of influenza infection in mice.

Reactive oxygen intermediates (ROI) and cytokines, particularly tumor necrosis factor (TNF) have been implicated in the pathogenesis of influenza. Using a murine model of influenza, we have studied the levels of TNF, interleukin 6 (IL-6) and of superoxide-generating xanthine oxidase (XO). Mice infected intranasally with influenza virus APR/8 had high levels of XO, TNF and IL-6 in the broncoalveolar lavage, as early as 3 d after infection. XO was elevated also in serum and lung tissue. Administration of the antioxidant N-acetylcysteine (NAC,1 g/kg per day, orally) significantly decreased the mortality in infected mice, indicating a role for RO1 in the lethality associated with influenza infection.

Journal Article↗
PubMedDate not supplied

Quality assurance in pathology. Cytologic and histologic correlation.

In this study we used a computerized program to compare the cytologic and histologic diagnoses made in a three-year period with the aim of evaluating the data obtained as an index of the diagnostic accuracy of cytology in a pathology quality assurance program. Concordance between the cytologic and histologic diagnoses was observed in 83.2% of the cases. In 1.2% the cytologic diagnosis was suspected malignancy, and 78.4% of these cases were positive for tumor at histologic examination. Analysis of the data must be performed in accordance with the anatomic site involved, and discordance must be investigated by a pathologist, especially in view of the different modalities of cytologic and histologic sampling. Analytic data on the breast, bladder and lung are presented.

Cell Biology↗
PubMedDate not supplied

Fine needle aspiration cytology of insular thyroid carcinoma. A report of four cases.

Four cases of poorly differentiated (insular) thyroid carcinoma (ITC) that underwent preoperative fine needle aspiration cytology were studied for the main cytologic features. Although ITC shows heterogeneity of histologic patterns, there are some cytologic characteristics suggesting the correct diagnosis, such as the presence of high cellularity, with large sheets of tumor cells showing a microfollicular pattern or smaller sheets showing a solid or trabecular pattern, intermingled with predominantly single cells on a hematic background with very scanty colloid. Nuclear overlapping is constant. The cytoplasm is poorly outlined, when present. Nuclear hyperchromasia is always present, with coarsely or finely granular chromatin. The variation in nuclear shape and size is moderate, with small nucleoli and occasional mitoses. A papillary arrangement, with the presence of intranuclear cytoplasmic inclusions (vacuoles) and nuclear grooves, is also visible.

Adolescent↗
PubMedDate not supplied

[Primary neuroendocrine carcinoma of the skin: histologic, immunohistochemical and ultrastructural study of a case with highly aggressive biological behavior].

We report a histological, immunohistochemical and ultrastructural study of a case of neuroendocrine carcinoma of the skin, which occurred in a 52 years old woman in the dermal, subcutis and soft tissues of the left buttock. Clinically this neoplasm, which was related to intramuscular injections and a to a following abscess, had rapidly reached unusual dimension compared with other cases of neuroendocrine carcinoma of the skin reported in the literature. The patient died three months after presentation with distant metastases. A variable percentage of the neoplastic cells was positive for low molecular weight cytokeratins (CK), neurofilaments (NF), neuron specific enolase (NSE) and occasionally for vaso-intestinal polypeptide (VIP). Ultrastructural investigations showed two types of neoplastic cells, identified for some features of the nucleus and of the cytoplasm; these two groups of cells are, in our opinion, related to different stages of cellular development. Our results, in agreement with some observations reported in the literature, give evidence of a possible origin of neuroendocrine carcinoma of the skin from an undifferentiated cell which is capable of neuroendocrine or ectodermal differentiation.

Abscess↗