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Biomedical subjects

J J Marx

Publications and source records attributed to J J Marx.

At least 145 records · Page 8Linked to original sources
PubMed1984

Deferoxamine enhances phagocytic function of human polymorphonuclear leukocytes.

Inhibition of the iron-mediated generation of toxic oxygen species by polymorphonuclear leukocytes (PMN) might prevent oxidative damage and thus enhance phagocytic function of PMN. To investigate this point, we studied the effect of the specific iron chelator, deferoxamine, on the antibacterial function of PMN. PMN were incubated for 20 hr with various concentrations of deferoxamine at 37 degrees C in medium containing 0.54 microM endogenous iron. The cells were then washed, and the phagocytic cell function was assessed. The results were compared with those for control PMN preincubated for 20 hr without deferoxamine, and those of nonincubated PMN. Compared with that of control PMN, the uptake of radiolabeled Staphylococcus aureus by PMN treated with 1 microM-1 mM deferoxamine was, on average, 10%-20% higher. This effect was not observed when iron-saturated deferoxamine (DFO) was used. Bacterial uptake was similarly increased in nonpreincubated PMN or PMN preincubated for 20 hr at 4 degrees C instead of 37 degrees C. The intracellular killing capacity of both deferoxamine-treated and control PMN exceeded 90%. PMN incubated for 20 hr at 37 degrees C with DFO not only phagocytosed more bacteria than control cells, but were also capable of killing the greater number of bacteria ingested. This increased activity of deferoxamine-treated PMN was accompanied by enhanced generation of chemiluminescence and production of superoxide during phagocytosis of S. aureus. These findings indicate that deferoxamine may enhance the antibacterial activity of PMN by protecting the cells against damage by iron-mediated generation of toxic oxygen metabolites in resting PMN.

Blood Bactericidal Activity↗
PubMed1984

Effect of iron (III) in the presence of various ligands on the phagocytic and metabolic activity of human polymorphonuclear leukocytes.

FeCl3 or Fe(III) that attached to chelating ligands such as citrate or nitrilotriacetic acid (NTA) at a molar ratio of 1:1 had a toxic effect on PMN. Uptake of radiolabeled Staphylococcus aureus by PMN, preincubated for 2 hr at 37 degrees C in a medium containing Fe(III)-citrate or Fe(III)-NTA, was significantly lower than that of control PMN preincubated without excess iron (p less than 0.002). However, at a 1:2 molar ratio of Fe(III) to citrate or NTA, the iron was not toxic. In contrast, the iron-liganding molecules transferrin and deferoxamine protected the PMN against the noxious effect of iron at concentrations just high enough to sequester all the iron. Fe(III) increased the generation of luminol chemiluminescence by stimulated PMN, whereas the oxygen consumption of the cells was not altered in the presence of Fe(III); this suggests a catalytic effect of iron on the production by PMN of oxygen metabolites at some step beyond the formation of superoxide. No effect of iron was observed when the incubation was performed at 4 degrees C, nor when an oxygen-radical scavenger such as thiourea, mannitol, or catalase was present in the incubation medium. Also, Fe(III) had much less effect on the phagocytic function of PMN of a patient with chronic granulomatous disease. The results indicate that the Fe(III)-induced defect in the phagocytic capacity of PMN depends on the nature and the concentration of the ligand attached to the iron ion, and also suggest that the noxious effect of iron on the PMN function is a result of its ability to catalyze the generation of toxic oxygen species by these cells.

Blood Bactericidal Activity↗
PubMed1983

Influence of heat treatment on rabbit liver ferritin.

Ferritin was purified from rabbit livers either by heat treatment and immunoaffinity chromatography, or by immunoaffinity chromatography alone. The immunoreactivity of ferritin with antibodies raised against heat-treated ferritin was significantly higher for heat-treated preparations than for non-heated preparations. The amount of ferritin protein could be estimated with equal reliability by the assay according to Lowry et al. and by nitrogen determination. Heat treatment favoured the L-subunit-rich ferritin fraction, as measured by densitometric scanning of SDS gradient-pore polyacrylamide gels. Amino acid analysis showed small changes in the amounts of valine, isoleucine and histidine in the heat-treated ferritin, possibly due to selective partial degradation of H-subunit-rich forms of ferritin. These results illustrate that heat treatment, which is a commonly used step in most purification procedures, induces partial denaturation of the ferritin molecules.

Amino Acids↗
PubMed1983

Inhibition of bacterial multiplication by the iron chelator deferoxamine: potentiating effect of ascorbic acid.

Since iron is essential for the multiplication of microorganisms, the effect of the iron chelator deferoxamine, with or without ascorbic acid, on the growth of 43 strains of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Alcaligenes faecalis, Neisseria meningitidis and species of Salmonella, Enterobacter, Pseudomonas and Providencia, was investigated with the use of an automated turbidimeter. Addition of deferoxamine (25-400 micrograms/ml) to the incubation medium was inhibitory in a dose-dependent fashion. At concentrations between 200-400 micrograms/ml, growth was about 25% lower than control values. However, when ascorbic acid (100 micrograms/ml) was added to the culture medium, this antimicrobial activity of deferoxamine was significantly increased to on average 75% of the control value (p less than 0.05). Ascorbic acid alone had no bacteriostatic properties. Growth in the presence of 200 micrograms/ml deferoxamine combined with 100 micrograms/ml ascorbic acid was significantly lower than that in control media without additions (p less than 0.001). Addition of ferric citrate to the culture medium at a concentration sufficient to saturate all of the deferoxamine with iron, abolished the growth inhibiting effect of deferoxamine. The results provide evidence that deferoxamine is bacteriostatic due to its capacity to deplete iron which would otherwise be used for bacterial multiplication, and that ascorbic acid enhances this antibacterial property of deferoxamine.

Alcaligenes↗
PubMed1983

Preparative isolation of distinct molecular forms of rabbit liver ferritin using high-performance liquid chromatography.

Rabbit liver ferritin was separated to fractions of distinct molecular form using a chromatofocusing column coupled to high-performance liquid chromatography equipment. This purification method was fast, less than 1 h, and enabled preparation of fractions, highly enriched in particular subtypes of ferritin. Analytical isoelectrofocusing of these fractions demonstrated a gradual shift in the range of isoelectric points of these subtypes of ferritin. Gradient-pore polyacrylamide slab-gel electrophoresis showed a distinct shift in the subunit ratio of the ferritins, ranging from 87% low molecular weight (L) subunit in the first fraction eluting at a pH 5.4, to 28% L-subunit in the fraction eluting in the trailing edge of the protein peak at pH 4.0. The pI range of the fractions covered the complete range, from pH 4.9 to pH 5.4, of isoelectric points of the whole rabbit liver ferritin preparation.

Animals↗
PubMed1983

Influence of heat-treatment on rabbit liver-ferritin kinetics.

Rabbit liver-ferritin was purified by heat-treatment and immuno-affinity chromatography or by immuno-affinity chromatography alone. The ferritin was labelled with 125I and injected into rabbits. Significant differences between the two preparations were observed in the rate of clearance from plasma. The biological half-life in vivo of the heat-treated samples was 5.3 +/- 0.5 min, and of non-heated preparations 8.5 +/- 0.5 min, thereby showing a significant (P less than 0.001) affect on the final preparation of heat-treatment during the isolation procedure. After the first 10-15 min period the clearance rate of a slower disappearing fraction was not dependent on the purification method used. The smaller amount of that fraction present in the heat-treated preparation, however, implies a selective loss of ferritin forms with a slow plasma clearance during the isolation procedure that includes heat-treatment.

Animals↗
PubMed1983

Isolation and possible relevance of Thermoactinomyces candidus proteinases in farmer's lung disease.

The thermophilic actinomycetes are the most common etiological agents causing hypersensitivity pneumonitis. Antigen preparations of these organisms contain proteolytic activity. Further investigation of the proteinases of the thermophilic actinomycetes was undertaken to determine whether this activity may contribute directly to the pathogenesis of hypersensitivity pneumonitis and pulmonary mycotoxicosis. The presence of proteolytic activity in aerosolized dust from moldy silage was demonstrated, and antibodies to two proteolytic enzymes from Thermoactinomyces candidus were found in the blood of farmer's lung patients who had been sensitized to this organism. These two enzymes were isolated from culture filtrate antigen preparations that had been partially characterized with respect to the proteolytic activities and their interaction with human serum proteinase inhibitors. Both proteinases belonged to the serine class of endopeptidases. Neither proteinase was inhibited by alpha 1-proteinase inhibitor or alpha 1-antichymotrypsin. Both proteinases were inhibited by alpha 2-macroglobulin. One of the proteinases had elastase activity. Inhalation of these proteinases apparently does occur, and they may induce an inflammatory response in the lungs since they are not inhibited by the main proteinase inhibitors protecting the lung.

Antibodies, Fungal↗
PubMed1983

Cheese worker's hypersensitivity pneumonitis.

A patient employed in a plant where blue cheese was manufactured developed hypersensitivity pneumonitis to Pencillium roqueforti. Symptoms of cough, dyspnea, and malaise, and findings of bibasilar crackles, reduced lung volumes, hypoxemia, and bilateral infiltrates on chest roentgenogram, resolved after she left the workplace. Bronchoalveolar lavage revealed a high percentage of lymphocytes. Antibody to P. roqueforti was demonstrated in serum and lavage fluid. To our knowledge this case represents a new occurrence of hypersensitivity lung disease in the cheese manufacturing industry in the United States.

Adult↗
PubMed1982

Listeria monocytogenes meningitis and decreased phagocytosis associated with iron overload.

A patient with Listeria monocytogenes meningitis was found to have idiopathic haemochromatosis and monocytes with reduced phagocytic capacity. The phagocytic function recovered completely after a series of therapeutic phlebotomies. In-vitro iron had a deleterious effect on the phagocytic capacity of monocytes and granulocytes. These findings show that iron overload in the host can increase susceptibility to L monocytogenes infection not only by increasing the virulence of the organism but also by reducing the phagocytic capacity of the monocytes.

Bloodletting↗
PubMed1982

Mucosal uptake, mucosal transfer and retention of a therapeutic dose of iron.

The absorption of a pharmacological dose of iron was assessed by determination of mucosal uptake, mucosal transfer and retention of 33 mg (Fe(II) as ferrous sulphate and ferrous ascorbate. 20 subjects were studed in a cross-over trial, 11 with normal iron stores and 9 with iron deficiency according to the serum ferritin concentrations. The activity of 59Fe and 51Cr (administered as a non-absorbable indicator) was measured by whole-body counting. There was no difference in absorption between the two iron compounds in normal subjects. Absorption of ferrous ascorbate averaged 52% higher than ferrous sulphate in subjects with iron deficiency. The difference was the result of higher mucosal uptake, probably because oxidation of Fe(II) in the alkaline milieu of the intestine, which leads to formation of non-absorbable Fe(III) complexes, was prevented. The mucosal transfer fraction of both compounds was identical.

Administration, Oral↗
PubMed1982

Molecular aspects of the binding of absorbed iron to transferrin.

To study the molecular aspects of the binding of absorbed iron to plasma transferrin, 59Fe with high specific activity was administered via intragastric tube to iron-deficient rabbits. The distribution of the absorbed 59Fe among the molecular forms of iron-transferrin was analysed using urea-polyacrylamide gel electrophoresis. Absorbed iron was bound to circulating transferrin one atom at a time. In four out of five animals, absorbed iron was predominantly bound to the site in the N-terminal domain of the protein. Thus, the two sites of transferrin may differ in their ability to load absorbed iron.

Animals↗
PubMed1981

Skin testing in farmers' lung disease.

Intradermal skin tests with a culture filtrate antigen of Micropolyspora faeni grown on a synthetic medium were performed on patients with farmers' lung disease (FLD) and well farmers with and without antibodies to a panel of FLD antigens. Seventy-five percent of the FLD patients, 79% of the well farmers with M. faeni antibody, and 5% of well farmers without M. faeni antibody had a 2+ or greater intradermal immediate skin-test reaction. Prausnitz-Küstner (P-K) reactions were positive using serum of M. faeni immediate skin test-positive FLD patients. IgG-rich fractions from a staphylococcal protein A-Sepharose column of such serum contained the sensitizing factor whereas IgG-depleted fractions did not. M. faeni-specific IgE could not be detected in serum by a polystyrene radioimmunoassay. Positive late-onset (6-hr) skin tests occurred only in FLD patients and farmers with precipitating antibody. Biopsy specimens of the 6-hr reactions revealed a generalized dermal and perivascular polymorphonuclear infiltrate with deposits of immunoglobulin and complement about blood vessels. The skin-sensitizing factor noted in FLD patients and well farmers with antibody is not disease specific. This factor appears to be associated with the IgG-rich fraction of serum, and its role in the pathogenesis of FLD is unclear.

Enzyme-Linked Immunosorbent Assay↗