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Biomedical subjects

M Signorini

Publications and source records attributed to M Signorini.

At least 73 records · Page 4Linked to original sources

Preliminary clinical experiences with the use of immunomodulators in burns.

The remarkable progress achieved in control of infections in burned patients has significantly increased survival rates. Nevertheless, septic complications are still the leading cause of death in these patients. The immunologic disturbances present after severe burns certainly play a key role in susceptibility to infection, and in particular the impairments of the phagocytic system warrant major investigative efforts in order to increase host defenses. Determination of phagocytic and microbicidal capacity of neutrophils from burned patients evidenced a marked functional impairment of these cells. The alterations recorded were partly due to intrinsic (cellular) defects, and partly to extrinsic (serum) defects. Indeed, opsonic factors are known to be reduced in these patients, but also phagocytosis-inhibiting factors such as immunocomplexes have been detected in the patients we have studied. Administration of the immunomodulating agents methysoprinol and timostimoline were found to be effective in partially restoring neutrophil function. Rational immunotherapy in burned patients will consist of replacement of humoral mediators, clearance of inhibitory factors and stimulation of the cellular effectors of immunity.

Adjuvants, Immunologic↗

The effect of inorganic phosphate on the stability of some enzymes.

In the presence of 5nM-P1, 6-phosphogluconate dehydrogenase from the yeast Candida utilis is more resistant to proteolysis and to the inactivating action of some chemical and physical agents. P1 also protects other enzymes against proteolysis. A hypothesis for the mechanism of the stabilizing action of P1 is advanced.

Candida↗

Evidence for multiple pairs of vicinal thiols in some proteins.

The oxidizing agent periodate has been used as an analogue of phosphate. The reaction of periodate with some enzymes which have a phosphate-binding site causes only the formation of disulfide bridges and the loss of the catalytic activity. Phosphate and other tetrahedral anions protect against inactivation. Other enzymes are not inactivated by periodate, which seems to be specific for vicinal thiols. The results obtained suggest (a) the use of periodate for the detection of vicinal thiols in proteins, (b) the presence of multiple pairs of vicinal thiols in the proteins tested, and (c) the presence of these pairs at a phosphate-binding site. An hypothesis on the chemical structure of the phosphate-binding site of some proteins is advanced.

Alcohol Oxidoreductases↗

Mutagenic epoxide impurities discovered in two new beta-adrenergic blocking agents.

Preparations of two new beta-adrenergic blocking drugs, Zami 1305 [1-(2-nitro-3-methyl-phenoxy)-3-tert-butylaminopropan-2-ol] and Zami 1327 [1-(6-nitro-3-methyl-phenoxy)-3-tert-butylaminopropan-2-ol], were found to be contaminated by expoxides which are direct acting mutagens on TA 100 and TA 1535 in the Salmonella/microsome mutagenicity test. Because of the suggested correlation between mutagenicity and carcinogenicity of a chemical [10,11], beta-adrenergic blocking agents contaminated by mutagenic expoxide impurities may be a health hazard.

Adrenergic beta-Antagonists↗

Affinity labelling of the NADP+-binding site of glucose 6-phosphate dehydrogenase from Candida utilis.

1. Periodate-oxidized NADP+ inhibits the catalytic activity of glucose 6-phosphate dehydrogenase from Candida utilis, competing with NADP+. 2. Incubation of the enzyme with the coenzyme analogue causes partial reversible inactivation of the enzyme as a result of affinity labelling of the coenzyme-binding site. 3. Some kinetic values of the reaction were calculated. 4. The inactivation can be made irreversible by treatment with NaBH4, which reduces a Schiff base formed between an aldehyde group on the coenzyme analogue and a lysine residue on the enzyme. 5. Complete inactivation can be correlated with the binding of only one inhibitor to each enzyme subunit. 6. The lysine residue involved in the binding of the inhibitor is present at the coenzyme-binding site.

Affinity Labels↗