Kinetic studies on rat liver low M(r) phosphotyrosine protein phosphatases. The activation mechanism of the isoenzyme AcP2 by cGMP.

The reaction mechanisms of p-nitrophenyl phosphate hydrolysis catalyzed by two rat liver isoenzymes of the low M(r) phosphotyrosine protein phosphatase (AcP1 and AcP2) were compared. Furthermore, the effect of some heterocyclic compounds on their activities were tested. Cyclic GMP and guanosine causes a particularly high activation of the isoenzyme AcP2, whereas its effect on AcP1 is very poor. A study on the mechanism of cyclic GMP activation was carried out. The results suggest that cyclic GMP activates the AcP2 isoenzyme by increasing the rate of the step that leads to the hydrolysis of the covalent enzyme-substrate phosphorylated complex formed during the catalytic process. The physiological significance of cyclic GMP activation of only one of the two isoenzymes (AcP2) remains uncertain.

3H-NECA binding to polymorphonuclear membrane: effect of sera from patients with Hodgkin's disease.

Several studies have shown that sera from patients with Hodgkin's disease contain factors capable of inhibiting polymorphonuclear functions, among them chemotaxis. In the present study, we investigated whether these sera, which were able to inhibit PMN chemotaxis in the agarose test, were also able to affect the 3H-NECA binding to PMN membrane obtained from healthy donors. Control experiments were carried out using PMN incubated with a pool of sera from healthy volunteers. No significant difference was found in the maximum number of binding sites; on the contrary, the equilibrium dissociation constant was significantly increased in the membrane preparation of PMN incubated with pathological serum.

Inhibition of leukocyte function by serum from patients with trichinellosis.

Modification of leukocytic function has been reported in only a few human parasitic diseases. In this study we evaluated the effects of the sera from patients infected with Trichinella on chemotactic and phagocytic responses in leukocytes. Leukocyte chemotaxis was tested by the agarose method and phagocytosis by the technique of Yamamura, modified for Saccharomyces cerevisiae. Sera were acquired from patients during a trichinellosis outbreak that occurred in northern Italy in 1986. The parasite was isolated from 1 patient and isoenzymatically typed as Trichinella sp. 3, a new taxon, previously considered Trichinella nelsoni. The results indicated that sera from Trichinella-infected humans inhibited both chemotaxis and phagocytic responses in leukocytes. These findings suggest the existence of serum factor(s) in trichinellosis patients that modify host leukocytic functions. The source and nature of active serum components and the mechanism by which they modulate leukocyte function remain to be clarified.

Effect of N-acetylcysteine in subjects with slow pulmonary mucociliary clearance.

There is significant evidence that in the general population there are subjects either with fast or slow pulmonary mucociliary clearance rates. At the moment we do not know the physiological importance of such finding. Slow clearers should be regarded as a subpopulation at risk for bronchopulmonary diseases. Therefore, it would be of considerable interest if their mucociliary function could be stimulated by drugs for preventive purposes. Twelve apparently healthy subjects with slow mucociliary clearance rate, selected in an epidemiologic survey in a non-smokers population were given 0.6 g oral N-acetylcysteine/day/60 days in a double-blind cross-over randomized study. After treatment their mucociliary clearance rates increased by about 35% as compared with baseline values, and returned to pre-treatment values after the washout period. Subjects were unresponsive to placebo treatment. It would seem that slow clearers are protected against lung aggressions by prevention and/or mucus-active drugs.

Methisoprinol restoration of leukocyte chemotaxis inhibition by blocking factors in immunoproliferative diseases.

The ability of methisoprinol to antagonize the serum-inhibiting activity present in the sera of patients affected by immunoproliferative diseases (Hodgkin's disease and multiple myeloma) was investigated. Using a chemotaxis test, it was found that whereas donor leukocytes preincubated in patient sera exhibited impaired chemotaxis, the presence of methisoprinol (500 micrograms/ml) during the preincubation caused a significant recovery of this leukocyte function. Since the results exclude the assumption of a non-specific stimulation of cell motility, two hypotheses appeared possible for the action of methisoprinol: either an antagonistic activity against the blocking factor at the receptor or the metabolic level, or a direct inactivation of this factor. The clinical implications, with regard to the prophylaxis of infections and a better response to chemotherapy, are discussed.

Effects of lithium carbonate on leukocyte functions in chronic benign neutropenia.

The effects of lithium carbonate on leukocyte functions in a case of chronic benign neutropenia are presented. Lithium was able to induce leukocytosis and to bring about increases in chemotaxis, marrow granulocyte reserve test and phagocytosis. After lithium interruption, leukocyte functions returned to initial values. Some hypotheses are advanced to account for lithium action.

Cell-mediated immunity in male fertility. Immunological infertility in man.

The leukocyte migration inhibition test on agarose was performed on 210 patients with different andrological disorders: oligozoospermia following primarily testicular disorders, oligozoospermia following primarily non testicular disorders and idiopathic oligozoospermia. This test was most applicable in disorders involving testicular damage and in cases of varicocele with altered blood flow. It would appear that cell-mediated immunity is involved in the pathogenesis of the consequences of these disorders.