Biomedical subjects
Publications and source records attributed to M Signorini.
When human endometrial transglutaminase was measured a 10-fold higher activity was detected during the secretive phase. This change was not related to either differences in solubility of the enzyme or to selective contamination by plasma factor XIII and rather appears to depend on the expression of the tissue form of transglutaminase, suggesting that this enzyme is regulated in vivo by progesterone.
Purified transglutaminase from human erythrocytes was shown to undergo time dependent inactivation by acrylamide added at millimolar concentration: this effect was wholly dependent on calcium ions and some protection was produced by glutamine substrates and GTP. The enzyme activity was recovered by addition of thiol based reducing agents, while ascorbic acid and sodium borohydrate were ineffective. These data are suggestive of an active site directed action of acrylamide.
The guanine nucleotides GTP, GDP and GMP inhibit the activity of erythrocyte transglutaminase (protein-glutamine:amine gamma-glutamyltransferase, EC 2.3.2.13) in a decreasing order of effectiveness. The inhibition is more apparent at low than at saturating levels of calcium ions and is not due to the chelation of Ca2+, but to an interference with the process of activation by the cation. This inhibition is likely to contribute to the latency of erythrocyte transglutaminase in physiological conditions.
The first cause of death in burned patients is still sepsis. A great number of studies point out a serious immunodeficiency due to several circulating mediators. Nowadays early excision and plasma exchange appear to be the most efficient procedures in order to remove from the patient these circulating agents. Therefore in this study the authors have treated 8 patients (average age 25 years), who presented an average of total burned surface of 49%, with plasma exchange performed early after injury. The results of PMN and lymphocyte function tests showed a significant therapeutic correction of these parameters in patients treated with plasma exchange. The clinical observations agreed with the results: in 7 patients with positive outcome, no invasive infections were recorded. The positive results obtained warrant further investigation with this procedure.
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Glycogen synthetase from skeletal muscle is rapidly inactivated by DEPC. In the presence of the substrate UDPG only 50% of the enzyme activity is lost. The concomitant addition of both UDPG and the allosteric activator glucose-6-phosphate almost completely prevents the inactivation by DEPC. Since glucose-6-phosphate alone does not prevent the inactivation by DEPC, it is concluded that it is effective through a potentiation of the effects of UDPG, possibly through a conformational change of the enzyme.
Uridine diphosphoglucose pyrophosphorylase was purified 2500-fold from rabbit skeletal muscle with a total recovery of 35% of the initial activity. The present procedure was made possible by an extensive use of hydrophobic chromatography. Purified pyrophosphorylase had a specific activity of 500 mumol/min/mg of protein and was homogeneous by chromatographic and electrophoretic criteria. The enzyme appears to be composed of eight subunits of 53,000 molecular weight each.
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The kinetic properties of rabbit muscle uridine diphosphoglucose (UDP-Glc) pyrophosphorylase have been studied, in both directions, with respect to substrate saturation, product inhibition, and cation requirement for activity. The results demonstrate that UDP-Glc pyrophosphorylase is a non-Michaelian enzyme: the synthetic reaction is characterized by a marked inhibition by glucose-1-phosphate (at concentrations higher than 0.3 mM) and by an hyperbolic saturation for UTP. In the reverse reaction, instead, the saturation function for UDP-Glc is hyperbolic and that for inorganic pyrophosphate is sigmoid, with a high Hill coefficient of (nH) 2.5. The study of the metal requirement indicates a distinctive ability of cations to stimulate the reactions of synthesis and degradation of the sugar nucleotide and a different stoichiometry of the metal chelates involved. The reaction mechanism is of the ordered-sequential type and the data of product inhibition allowed the identification of glucose-1-phosphate as the first substrate bound and UDP-Glc as the last product released. The inhibition pattern by UDP-Glc gives evidence for cooperativity also in the binding of this molecule.
Incubation of skeletal muscle glycogen phosphorylase with sodium periodate's results into irreversible loss of enzyme activity. The rate of inactivation is influenced by the ionic strength of the medium and by the presence of caffeine, but not by nucleotides. During the reaction, cysteine residues slowly reactive towards DTNB are modified and the coenzyme is released. These results suggest the presence of cysteine residues at the protein site involved in the binding of the phosphate group of pyridoxal phosphate.
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.
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