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Biomedical subjects

M F Cossu

Publications and source records attributed to M F Cossu.

10 recordsLinked to original sources

[Cytokines and renal injury].

Cytokines play an important role in most physiological and pathological processes. In this note the authors review recent literature data about cytokines in mediating renal inflammatory diseases. These molecules are involved in every phase of inflammatory injury induce expression of MHC class II and adhesion molecules on renal cells, synthesis of chemoattractants; they are also involved in leukocyte localization and play a role in the induction of cell proliferation and the accumulation of extracellular matrix. The disturbances of the cytokine network may lead to inflammatory kidney disease that could be treated by novel therapeutic agents like anticytokine antibodies.

Animals↗

Study of the growth factors for the mammary gland: epidermal growth factor and mesenchyme-derived growth factor.

The physiological importance of EGF in the development of the mouse mammary gland during pregnancy and in spontaneous mammary tumorigenesis has been documented by a series of experimental results presented herein. In our study, we have taken a variety of experimental approaches including radioimmunoassay of EGF in the submandibular gland and plasma, mammary gland organ/cell culture, EGF receptor assay, sialoadenectomy and treatment with EGF and EGF antibodies to assess the role of EGF in the mammary gland. In particular, studies employing sialoadenectomy and EGF replacement have provided valuable information concerning the function of EGF in the body. These studies are possible in the mouse system because the submandibular gland serves as a major source of circulating EGF and also because purified mouse EGF is available commercially. Our work on the biological, endocrinological, and physiological aspects of EGF in normal and neoplastic growth of the mammary gland should be useful for the study of the regulation of mammary gland growth at the molecular level as well as for clinical investigations of mammary tumors. Finally, our findings of a mammary growth factor in embryonic mesenchymal cultures suggest the possible involvement of paracrine growth factor(s) in mammary cell growth. Further progress in this area is needed for better understanding of the complex process of mammary gland growth and development.

Animals↗

Involvement of the Ca2+-dependent K+ channel activity in the hyperpolarizing response induced by epidermal growth factor in mammary epithelial cells.

Epidermal growth factor (EGF) induces a hyperpolarizing response of 5-20 mV amplitude in mouse mammary epithelial cells in culture. The amplitude of the hyperpolarizing response was reduced by more than 60% within several minutes after addition of blockers of voltage and/or Ca2+-dependent K+ channels such as tetraethylammonium (7 mM) or quinine (0.29 mM). Both nifedipine (0.15 mM), a blocker of the Ca2+ channel, and ruthenium red (2 mM), an inhibitor of the Ca2+-binding site, also reduced the amplitude of the hyperpolarizing response by more than 60%. The Ca2+ ionophore, A23187 (3.8 microM), induced a large hyperpolarization, which was 25-40 mV and lasted about 3 min. These data suggest that activity of the Ca2+-dependent K+ channel was involved in the EGF-induced hyperpolarizing response of the mammary epithelial cells.

Animals↗

Induction of distinct types of spontaneous electrical activities in mammary epithelial cells by epidermal growth factor and insulin.

Electrophysiological measurements of the membrane potentials of mouse mammary epithelial cells in primary culture revealed the presence of spontaneous-oscillating-hyperpolarizing potentials in cells incubated with epidermal growth factor. The hyperpolarizing potentials were 5-20 mV in amplitude and about 10 sec in duration. The peak height of the response was reduced by hyperpolarization, and the input membrane resistance decreased during the response. The response was probably due to activation of K+ channels. The latency period for the epidermal growth factor induction of the hyperpolarizing potential was approximately 3 hr. In contrast, insulin induced spontaneous-depolarizing potentials that were about 5 mV in amplitude and 1 sec in duration. The depolarizing potentials were attributed to activity of ion channels, since the peak height was dependent on the membrane potential and the depolarizing potential was accompanied by a decrease of input membrane resistance. The time lag for the induction of the depolarizing potential was 6-12 hr. Other hormones involved in mammary cell differentiation, such as cortisol and prolactin, neither induced the depolarizing potentials nor changed the induction of depolarizing potential by insulin. In addition, other growth factors, such as nerve growth factor and fibroblast growth factor, elicited no electrical activity.

Animals↗

Effect of vagotomy on TRH inhibition of acid gastric secretion.

The effect of slow (600 micrograms) and rapid (200 micrograms) infusion of TRH on acid gastric secretion was studied in a group of healthy volunteers and a group of patients treated by truncal vagotomy. It was shown that the slow (600 micrograms) TRH infusion does not act on gastric secretion in both groups, while the rapid (200 micrograms) TRH infusion appears to significantly decrease the parameters under study during the first 15 minutes of gastric juice collection.

Adult↗

Further characterization of the inhibition of casein production in a primary mouse mammary epithelial cell culture by epidermal growth factor. Antagonism by cyclic AMP.

Epidermal growth factor (EGF) inhibited casein production and the accumulation of casein mRNA activity induced by insulin (I), cortisol (F) and prolactin (P) in a primary culture of mammary epithelial cells from pregnant mice. The inhibitory effects of EGF were blocked by 8-bromo cyclic AMP (8-br-cAMP) in a dose-dependent manner. The effect of 8-br-cAMP was observed at a concentration as low as 20 microM and was maximal at 500 microM. Dibutyryl cyclic AMP (db-cAMP), cAMP, and 3-isobutylmethylxanthine (IBMX), an inhibitor of phosphodiesterase, also antagonized the inhibitory effect of EGF on casein production. 8-Br-cAMP had, however, no effect on the mitogenic activity of EGF in this system. These results suggest a possible modulatory role of cAMP in EGF-induced inhibition of casein production in cultured mammary epithelial cells.

8-Bromo Cyclic Adenosine Monophosphate↗

[The IgE system].

The IgE synthesis is regulated by a system of immunocompetent cells (B and T lymphocytes) and cytokines (IL-4, IFN gamma, IL-2, IL-5, IL-6) produced by T cells as a response to antigenic stimuli. IL-4 alone, or associated with other cytokines, determines the CD23+ receptor (FCERII) expression on monocytes-macrophages, eosinophiles, platelets, epidermidis Langerhans cells and B lymphocytes surfaces, inducing its cleavage in a Soluble Factor (IgE-BF), that increases the IgE synthesis. IFN-gamma, on the other hand, plays an inhibitory role on T-dependent phenomena, IL-4-mediated. In patients affected by atopic diseases, associated with oculorhinites, dermatitis and hyper-IgE syndrome, are found high serum levels of IgE, eosinophiles, and a large number of CD23+ cells: this indicates the hyper-reactivity of the IgE system and the IL-4 overproduction.

Animals↗

[Teichoplanin: a clinical study of treatment of serious infections in hospitalized patients].

The study was performed to evaluate the efficacy and the safety of teicoplanin in the treatment of serious Gram positive bacteria infections in hospitalized patients at high risk of complications. In a twelve month period, 13 patients were treated. Six of whom presented generalized infections with bacteremia and seven severe localized infections. Safety evaluation included pre, during and post treatment measurements of haematological and serum chemistry parameters. Clinical successes with microbiological eradication of pathogens were obtained in 11 out of 13 cases (84.6%). One persistence of infection (7.7%) and one Gram negative superinfection (7.7%) presented. Only in one patient we noted a transitory increase of creatinine level. Teicoplanin showed to be useful in the treatment of serious Gram positive infections in hospitalized patients.

Adult↗

[Increased plasma levels of endothelin in patints with essential arterial hypertension].

Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictive peptide. In this study the Authors measured in 25 subjects (15 with essential hypertension and 10 normal) plasma levels of endothelin-1. Patients with hypertension had significantly higher plasma ET-1 concentration than normal subjects (2.18 +/- 1.07 vs. 1.36 +/- 0.40 pg/ml, p < 0.02). Plasma arginine vasopressin, renin activity and aldosterone concentration did not show significant differences between hypertensive and normotensive subjects. These data suggest that ET-1 may be involved in the development or maintenance of hypertension.

Endothelins↗