Search PubMed⌕ Search

Biomedical subjects

J J Marx

Publications and source records attributed to J J Marx.

At least 127 records · Page 7Linked to original sources
PubMed1989

Lipid peroxidation of human granulocytes (PMN) and monocytes by iron complexes.

Because the phagocytic function of non-stimulated human polymorphonuclear granulocytes (PMN) is impaired after incubation with either polynuclear Fe(III) or Fe(II), we decided to study lipid peroxidation of PMN and monocytes by these iron complexes. Lipid peroxidation was assessed by measuring thiobarbituric acid reactive substances and fluorescent compounds. In this study we report that monocytes, isolated in the standard way (EDTA-mediated detachment), release significantly more thiobarbituric acid reactive substances after incubation with iron than PMN. Monocytes, however, isolated without EDTA release the same amount after incubation with iron as PMN. The iron complexes shown to impair phagocyte function also stimulated the peroxidation of membrane lipids. Ascorbic acid in high concentrations enhanced iron-induced lipid peroxidation. Lipid peroxidation induced by ferrous ascorbate (1:20) could be inhibited by catalase, the iron chelators deferoxamine and transferrin, and the hydroxyl radical scavenger thiourea. Mononuclear complexes (ferric citrate 1:20) did not impair granulocyte function and did not induce lipid peroxidation. Our results suggest that impaired phagocyte function in patients with iron overload may be due to non-transferrin bound iron-mediated peroxidation of membrane lipids. However, the lowest amount of ferrous ascorbate (1:20) capable of inducing lipid peroxidation (50 microM) was significantly higher than that which impaired phagocyte function (10 microM).

Ferric Compounds↗
PubMed1989

Continuous intravenous infusion of deferoxamine reduces mortality by paraquat in vitamin E-deficient rats.

Paraquat, an oxygen radical-generating agent, is a widely used agrochemical that is also toxic for humans, in whom it may cause respiratory failure. In the present study, we investigated the effect of deferoxamine (DF), an iron chelator with antioxidant capacity, on paraquat toxicity in vitamin E-deficient rats. After the administration of paraquat at a dose of 20 mg/kg the animals were treated with a continuous intravenous infusion of DF for 14 days. In a dose-response study, four of six animals receiving 100 mg DF/kg/24 h survived the study period of 14 days compared with none in the saline-treated control group (n = 6), and three and two animals in the groups receiving 50 (n = 6) and 200 mg DF/kg/24 h (n = 6), respectively. In another series of experiments, animals were monitored for a total period of 35 days, at which time any survivors were killed, and lung histologic examination was carried out. Deferoxamine treatment was started simultaneously (n = 21), 6 h (n = 18), and 16 h (n = 18) after paraquat poisoning. Percent survival in the various time-point groups was 47.7 (p less than 0.01), 38.9 (p less than 0.02), and 22.2 (not significant), respectively, compared with 7.1 (n = 14) in the control group. The presence of lung damage was seen only in those of the surviving rats where DF was started at the 16 h time point after paraquat administration. In ancillary in vitro studies, where Escherichia coli was used as a source of enzymic activity for the redox-cycling of paraquat, DF completely inhibited the formation of hydroxyl radical (.OH).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Lipid peroxidation of rabbit small intestinal microvillus membrane vesicles by iron complexes.

Fe(II)- and Fe(III)-induced lipid peroxidation of rabbit small intestinal microvillus membrane vesicles was studied. Ferrous ammonium sulphate, ferrous ascorbate at a molar ratio of 10:1, and ferric citrate, at molar ratios of 1:1 and 1:20, did not stimulate lipid peroxidation. Ferrous ascorbate, 1:1, induced low stimulation, while ferrous ascorbate, 1:20 gave higher stimulation of lipid peroxidation. These results show that in our experimental system, ascorbate is a promotor rather than an inhibitor of lipid peroxidation. Ferric nitrilotriacetate (at molar ratios of 1:2 and 1:10), at an iron concentration of 200 microM, was by far the most effective in inducing lipid peroxidation. Superoxide dismutase, mannitol and glutathione had no effect, while catalase, thiourea and vitamin E markedly decreased ferrous ascorbate 1:20-induced lipid peroxidation. Ferric nitrilotriacetate-induced lipid peroxidation was slightly reduced by catalase and mannitol, significantly reduced by superoxide dismutase, and completely inhibited by thiourea. Glutathione caused a 100% increase in the ferric nitrilotriacetate-induced lipid peroxidation. These results suggest that Fe(II) in the presence of trace amounts of Fe(III), or an oxidizing agent and Fe(III) in the presence of Fe(II) or a reducing agent, are potent stimulators of lipid peroxidation of microvillus membrane vesicles. Addition of deferoxamine completely inhibited both ferrous ascorbate, 1:20 and ferric nitrilotriacetate-induced lipid peroxidation, demonstrating the requirement for iron for its stimulation. Iron-induced peroxidation of microvillus membrane may have physiological significance because it could already be demonstrated at 2 microM iron concentration.

Animals↗
PubMed1988

Effect of iron on polymorphonuclear granulocyte phagocytic capacity: role of oxidation state and effect of ascorbic acid.

It has been shown that iron (III) impairs the function of polymorphonuclear granulocytes (PMN). We have studied the effect of iron (II), on the membrane function of PMN, by assessing the uptake of radiolabelled Staphylococcus aureus by these cells. Iron (II), significantly impaired PMN phagocytic function. Addition of ascorbic acid reduced uptake further. Ferrous ascorbate, molar ratio 1:20, impaired phagocytic capacity of PMN significantly at iron concentrations as low as 1-10 microM. The toxic effect of iron (II) was not observed when desferrioxamine or transferrin was present in the incubation medium. The oxygen-free radical scavengers thiourea, mannitol and catalase prevented toxicity mediated by ferrous ammoniumsulphate but not by ferrous ascorbate (molar ratio of 1:20). Although high concentrations of ascorbic acid inhibited the generation of .OH and also the formation of the DMPO-.OH adduct by zymosan stimulated PMN, toxicity of iron increased. Iron (II) impaired the uptake of S. aureus by PMN of a patient with chronic granulomatous disease while iron (III) did not. Iron mediated impairment of PMN function is not only a result of the generation of toxic oxygen metabolites but also of direct interaction of iron (II) or an iron (II)-oxygen intermediate with molecules of the cell membrane.

Adult↗
PubMed1988

Polynuclear iron complexes impair the function of polymorphonuclear granulocytes.

In a previous study we showed that the phagocytic function of non-stimulated PMN was impaired after incubation with high concentrations (200 microM) of polynuclear Fe(III), probably as a result of continuous generation of small amounts of superoxide and subsequent formation of hydroxyl radicals (Van Asbeck et al, 1984b). Because polynuclear Fe(III) complexes may not be available for biological reactions we have studied the effects of polynuclear and mononuclear iron(III) on the PMN. Fe(III) in its polynuclear form (Fe:citrate 1:1) was deleterious for the phagocytic function of PMN, while the mononuclear form (Fe:citrate 1:20) was not toxic. Binding affinity of polynuclear Fe(III) for PMN was higher than of mononuclear Fe(III), and a considerable amount of bound Fe(III) was found in the cytosolic fraction of non-stimulated PMN. Limit dilution analysis of polynuclear complexes revealed that concentrations as low as 25 microM Fe(III) significantly impaired phagocytic function. The molecular weight of these complexes is similar to that of the non-transferrin plasma iron found in the serum of patients with iron overload. The toxic effects of small polynuclear non-transferrin plasma Fe(III) complexes on PMN function may contribute to the development of infections in patients with iron overload.

Adult↗
PubMed1988

Decreased iron absorption in patients with active rheumatoid arthritis, with and without iron deficiency.

Mucosal uptake, mucosal transfer, and retention of a physiological dose of ferrous iron were studied in women with active rheumatoid arthritis (RA): 19 with normal and 17 with depleted bone marrow iron stores. Control subjects were 26 normal women and 20 women with uncomplicated iron deficiency. Iron absorption was measured with 59Fe as a tracer and by whole body counting. Compared with controls, final iron retention was considerably decreased in both groups of patients with RA. Analysis of the two sequential steps of iron absorption showed that mucosal uptake was normal in iron replete patients with RA but was significantly lower in patients with RA with depleted iron stores compared with iron deficient controls. Mucosal transfer of iron was considerably decreased in patients with RA with normal iron stores. The impaired absorption of iron in patients with active RA may delay the correction of the haemoglobin concentration when anaemia of chronic disease is complicated by iron deficiency.

Adult↗
PubMed1988

[Idiopathic pulmonary hemosiderosis].

Idiopathic pulmonary haemosiderosis is a rare disease of unknown etiology. It is most frequently seen in childhood. Three case histories are presented, backgrounds and therapeutic possibilities are discussed. Centralized registration is necessary for better understanding of the disease.

Anemia, Hypochromic↗
PubMed1987

An outbreak of organic dust toxic syndrome in a college fraternity.

An explosive outbreak of a febrile respiratory illness occurred among members of a college fraternity. The preponderant signs and symptoms were muscle aches, cough, and low-grade fever. All illnesses occurred within 1.3 to 13 hours of attendance at a party where there was a dense airborne dust from straw that had been laid on the floor. Of the 67 fraternity members who attended the party and answered a questionnaire, 55 became ill (attack rate, 82%). Risk of illness was higher for those who spent more time at the party. Duration of illness ranged from 4.5 hours to seven days. Results of serological studies did not demonstrate an allergic or viral cause for these illnesses. The clinical and epidemiologic features of this outbreak were characteristic of organic dust toxic syndrome, an acute respiratory illness caused by inhalation of molds growing on hay, silage, or other agricultural products.

Adult↗
PubMed1987

Intracellular magnesium of mononuclear cells from venous blood of clinically healthy subjects.

Measurement of intracellular magnesium (Mg2+) may have advantages over serum Mg2+ measurements in the assessment of Mg2+ homeostasis in patients. An accurate and reproducible method of measuring the Mg2+ content of mononuclear cells (lymphocytes and monocytes) from the venous blood of human subjects utilizing commonly available reagents and equipment is described. A well-defined clinical population of 88 subjects (48 males and 40 females) was used as the normal population. The mean mononuclear cell Mg2+ content was 67.8 +/- 13.8 (SD) fg/cell giving a 95% confidence interval normal range of 40-95 fg/cell which compared favorably to the empirical 95% limits of 44-94 fg/cell. The serum Mg2+ measured at the same time was 0.90 +/- 0.06 (SD) mmol/l. No significant correlation was found when comparing serum and mononuclear cell Mg2+ concentrations. Additionally, no significant differences were found when serum and intracellular Mg2+ were analyzed for sex and age with the exception that intracellular Mg2+ tended to be slightly higher in the younger age groups. The routine performance of this assay may require as little as 7 ml of venous blood and was done with a coefficient of variation of 3.0-3.6%.

Adult↗
PubMed1987

Influence of subunit composition of rabbit liver ferritin on its clearance from plasma.

1. Purified rabbit liver ferritin was separated into fractions composed of 87% light molecular weight, and 72% high molecular weight subunits. 2. Radiolabeled ferritin fractions, injected intravenously into rabbits, showed no differences in clearance kinetics. 3. Differences found in ferritin clearance from plasma do not depend on the subunit composition of different molecular species.

Animals↗
PubMed1986

Granulocyte dysfunction and myotonic dystrophy.

A 52-year-old Caucasian male with typical features of myotonic dystrophy (MD) developed a lung abscess and was found to have a mild atypical cyclic neutropenia. Granulocyte function testing revealed a defect in phagocytosis, bactericidal activity and chemotaxis. The defects were less severe at the nadir of the granulocyte counts. Skin windows demonstrated that the granulocyte defects were not just an in vitro artifact. The patient was treated with lithium carbonate and improved. Mobilization into a skin window and clinical MD were unchanged. Studies of his 10 children and 2 siblings, including granulocyte function tests and complete neurological evaluations were obtained. The 4 children with abnormal parameters of granulocyte function all had definite evidence of MD. Two children had equivocal findings of MD and the others were normal. There was minimal evidence of granulocyte dysfunction in these children. Twelve of 19 unrelated patients with MD had evidence of impaired granulocyte function with the most consistent defect being chemotaxis in response to bacterial factor. Mild granulocyte dysfunction is frequently associated with MD, but severe dysfunction with many defects is uncommon but can occur, as in this family. There was a tendency for the more severely afflicted members of this family to have more pronounced granulocyte dysfunction. Longitudinal testing in this family may determine any relationship between the granulocyte dysfunction and the onset of MD, as well as any correlation with the progression of the disorder. MD patients who develop infection should have granulocyte function tests as part of their evaluation.

Adolescent↗
PubMed1985

Monitoring of intensive phlebotomy therapy in iron overload by serum ferritin assay.

Four patients with idiopathic hemochromatosis were treated with intensive phlebotomy therapy. In 1 to 2 years, 8.8-16.7 g iron was removed. In three out of four patients hemoglobin levels fell at the end of therapy. Serum ferritin was continuously measured during therapy. The greatly elevated serum ferritin levels normalized or decreased to subnormal levels in all patients after therapy. Despite some fluctuations in the first phase of therapy, the fall in serum ferritin was regular with halving of the ferritin levels after about 50% of the excess iron was removed. The normalization of serum ferritin occurred in advance of the hemoglobin decrease at the end of therapy, indicating that in the later stages of therapy the normal iron stores are also depleted. It is emphasized that serum ferritin measurements are useful for monitoring of intensive phlebotomy therapy, and in particular to indicate the end of therapy before anemia develops.

Adult↗
PubMed1985

Iron and phosphorus content of rabbit liver ferritin fractions with different subunit composition.

After isolation of subtypes of rabbit liver-ferritin, the phosphorus to iron ratio (P/Fe-ratio) in the samples was found to parallel the shift in subunit composition of the two types of subunits of which ferritins generally consist. No relation was found with the amount of iron per ferritin molecule. The increase of the P/Fe-ratio, in relation to subunit composition, is postulated to be a result of the change of total surface area of the iron microcrystallites inside the ferritin molecule. This surface area depends on the number of nucleation points and thereby may be dependent on the subunit composition.

Animals↗
PubMed1984

Immunochemical studies of a purified antigen from Micropolyspora faeni.

A pure antigen fraction was isolated from the crude culture filtrate of Micropolyspora faeni by gel filtration and affinity chromatography. The isolated antigen has a mol. wt of approximately 16,000 and an isoelectric point of pH 3.8. The major amino acid content of this fraction includes glycine, glutamic acid, aspartic acid and alanine. This antigen fraction reacted with the sera of all 15 farmer's lung patients and 20 asymptomatic farmers with circulating anti-M. faeni antibodies. An ELISA method was developed using the purified antigen to detect specific circulating antibodies against M. faeni in farmer's lung patients.

Amino Acids↗
PubMed1984

Measurement of ferritin in serum: application in diagnostic use.

A sandwich-type radioimmunoassay for serum ferritin was developed using iron-rich human liver ferritin and evaluated for its clinical usefulness. In young healthy males and females, the mean serum ferritin concentrations were 44 micrograms/L (range 7-158) and 16 micrograms/L (range 4-56), respectively. In anemic patients lower serum ferritin concentrations were found, while in most patients with iron overload serum ferritin concentrations well above 1000 micrograms/L were measured. Comparison of our method with a commercially available radioimmunoassay kit revealed a good correlation, except for sera with very low ferritin concentrations. Comparison with serum iron and transferrin parameters in patients with iron deficiency demonstrated that serum ferritin concentrations might be subnormal in a majority of patients with otherwise normal iron indices. Up to 70% of the ferritin in serum of normal subjects could bind to concanavalin A-Sepharose, indicating its glycoprotein nature. It is concluded that our serum ferritin radioimmunoassay gave reliable results and was useful in the laboratory diagnosis of latent iron-deficiency and in the analysis of the heterogeneity of serum ferritin.

Adult↗
PubMed1984

Functional defects in phagocytic cells from patients with iron overload.

Phagocytic functions were studied in patients with iron overload. Phagocytosis of radiolabelled opsonised Staphylococcus aureus by mononuclear (MN) leucocytes and polymorphonuclear (PMN) leucocytes was measured in 15 and 16 patients, respectively. The intracellular killing capacity of MN and PMN leucocytes of seven and nine patients, respectively, and chemotaxis of PMN leucocytes of eight patients, were assessed also. These cellular functions were compared with phagocytic functions of controls tested on the same day, and with the normal ranges of phagocytic cell functions obtained with MN and PMN leucocytes from 48 and 59 healthy donors, respectively. One or more phagocytic functions were impaired in 62.5 per cent of the patients. Comparison of the various phagocytic functions in patients and simultaneously tested controls showed a significant decrease of the mean phagocytic capacity of the patients' MN and PMN leucocytes (P less than 0.015 and P less than 0.03, respectively), as well as the mean bactericidal activity of the MN leucocytes (P less than 0.05) and the mean chemotactic responsiveness of the PMN leucocytes (P less than 0.025). Patients with excess iron must be regarded as compromised hosts, not only because of the increased availability of iron for bacterial growth, but also because of the associated functional impairment of monocytes and granulocytes.

Adolescent↗