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Biomedical subjects

P Fondu

Publications and source records attributed to P Fondu.

At least 73 records · Page 4Linked to original sources

[The functions of iron in the defense against infections, and especially the importance of abnormalities in phagocytosis in iron overload].

The biological functions of iron result from its catalytic properties and from its ability to stimulate the formation of potentially toxic oxydant radicals. In living organisms, both properties are modulated or controlled by the interactions of the metal with specific proteins. Essential element for both man and pathogenic germs, iron exerts many functions which are crucial in the defence against infections. Both host and microorganisms possess mechanisms allowing them to harvest iron. Furthermore, the potential biological toxicity of the metal is utilized in the host's phagocytes. Iron deficiency and overload lead to complex alterations of these mechanisms and may predispose to some infections. One of these abnormalities concerns the phagocytosis of the polymorphonuclear neutrophils observed in iron overload. Recent studies conducted by our group confirm the hypothesis that these functional disturbances of polymorphonuclear neutrophils may be due to the autotoxicity of non protein bound iron.

Antibody Formation↗

Impaired neutrophil defense against Yersinia enterocolitica in patients with iron overload who are undergoing dialysis.

Increased risk that patients with iron overload who are undergoing dialysis will have bacteremia caused by Yersinia enterocolitica has previously been shown. Iron overload is known to increase the virulence of Y. enterocolitica. Whether alterations of the phagocyte defense against this organism are also involved has not yet been determined. We compared neutrophil defense against a serum-resistant strain of Y. enterocolitica in three groups of individuals: nine patients receiving hemodialysis who had iron overload (group 1), nine patients receiving hemodialysis who did not have iron overload (group 2), and 10 healthy controls (group 3). Y. enterocolitica phagocytosis and killing were studied in the presence of autologous or pooled normal human serum. Phagocytosis was significantly decreased in group 1 compared with that in the other two groups. The use of normal serum for opsonization did not improve the phagocytosis function. Killing was moderately decreased in the group 1, but only in the presence of autologous serum. We conclude that in patients with iron overload who are undergoing dialysis, the high frequency of Yersinia bacteremia is attributable not only to increased virulence of this microorganism but also to disturbances of the mechanisms specifically involved in the neutrophil defense against Yersinia invasion.

Blood Bactericidal Activity↗

Neutrophil dysfunctions in thalassaemia major: the role of cell iron overload.

The susceptibility to infections was recorded in 13 patients with beta thalassaemia major (T.P.). The following parameters were also investigated in their polymorphonuclear neutrophils (PMN): nitro blue tetrazolium (NBT) reduction, heated yeast and Escherichia coli phagocytosis, Escherichia coli killing and myeloperoxydase activity. These results were compared to those obtained in healthy controls (H.C.). The Perls's reaction was performed on PMN and graded according to a scoring system with the aim of quantifying the iron intoxication of PMN. Phagocytosis and Perls's reaction of PMN from H.C. were also studied after 20 h of incubation with thalassaemic serum. 6 T.P. out of 13 developed septicaemia during their lifetime and in all 9 septicaemic episodes were noted. Phagocytosis was greatly impaired, disclosing both cellular and serum abnormalities. The mean percentage of Perls's positive PMN was 13% in T.P., contrasting with the constant negative reaction in H.C. The incubation of PMN from H.C. with serum from T.P. induced the simultaneous appearance of a phagocytosis defect and of a positive Perl's reaction. It was concluded that in beta thalassaemia major the phagocytosis of PMN was altered due to a combination of serum and cellular abnormalities and that both may be related to the iron overload.

Adolescent↗

Deoxythymidine and deoxycytidine incorporation into DNA in B leukemic cells.

Measurements of radioactive DNA after incubation of normal and B leukemic peripheral mononuclear cells, from c-ALL and CLL with labeled deoxythymidine (dTh) and deoxycytidine (dCt) showed that for dTh, incorporation into DNA was similar for normal and c-ALL cells but lower in B-CLL cells and that for dCt, incorporation was highest in c-ALL and lowest in CLL cells. These results contrast with those of dTh and dCt kinase activities; the former has been previously found elevated in c-ALL cells, and the latter is found, in the present study, similar in the three groups tested.

B-Lymphocytes↗

Immunohistochemical distribution of glial fibrillary acidic protein, neurofilament polypeptides and neuronal specific enolase in the human cerebellum.

The human normal cerebellar cortex has been investigated using paraffin-embedded sections and a panel of antibodies against GFAP, NSE, NF 70 Kd and 200 Kd triplet proteins. The study has shown that: antiserum to GFAP labelled all and only astroglial elements; antibodies to NSE, NF 70 Kd and 200 Kd stained the perikaryon of all neurons, with two noticeable exceptions: Purkinje cells, which remained unresponsive to all 3 reagents, and basket cells which only became labelled with the NSE antiserum; the staining of dendrites and axons was exquisitely selective with both the NF and the NSE antibodies, each of which displayed unique binding patterns. These immunohistochemical features, first to be described in man, are compared with those so far reported in rodents.

Astrocytes↗

Impaired phagocytic activity of neutrophils in patients receiving haemodialysis: the critical role of iron overload.

The metabolic burst (as measured by the spontaneous and stimulated nitroblue tetrazolium tests), the phagocytosis of heat inactivated bakers' yeast and of Staphylococcus aureus, the killing of Staph aureus, and the myeloperoxidase activity of polymorphonuclear neutrophils were studied in 11 patients receiving maintenance haemodialysis. Of these patients, six were polytransfused and had high serum ferritin concentrations (mean 5940 (SD 2925) micrograms/l; group 1), and five had normal serum ferritin values (mean 171 (116) micrograms/l; group 2). Patients in group 1 had a history of more infectious episodes (0.167 v 0.025 per patient per month) and significantly more genitourinary infections (p = 0.015) than those in group 2. Phagocytosis and myeloperoxidase activity were severely reduced in group 1 but normal in group 2. Percentages of neutrophils ingesting one or more particles together with the index of phagocytosis in patients' serum were inversely correlated with serum ferritin concentrations. Four patients in group 1 were treated with desferrioxamine, and after six to 18 weeks of treatment phagocytosis and myeloperoxidase activity had returned to normal in three of them. These data suggest that in patients receiving haemodialysis iron overload due to multiple transfusions plays an important part in the mechanisms underlying the susceptibility to bacterial infections, mediated at least partially through impaired neutrophil function.

Adult↗