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Biomedical subjects

J J Marx

Publications and source records attributed to J J Marx.

At least 55 records · Page 3Linked to original sources
PubMed1999

Multi-drug resistance in chronic lymphocytic leukemia.

We evaluated 45 chronic lymphocyte leukemia (CLL) patients for the presence of multi-drug resistance (MDR) by the ex vivo techniques: 1) a functional assay utilizing doxorubicin (dox) retention with modulation; 2) a cytotoxicity assay (MTT) with modulation; 3) and four monoclonal antibodies. Ex vivo tests were correlated with disease stage and prior treatment, and were repeated as patients became resistant to alkylating agents, fludarabine and VAD chemotherapy (infusion of vincristine, dox, and oral dexamethasone). The majority of patients (64.4%) were in early stage and were untreated (62.2%). P-glycoprotein (p-gp 170) was detected most frequently by the monoclonal antibody MRK-16 (48%) and by functional modulation of dox retention by PSC-833 (40.6%) and by functional modulation of the MTT assay with vincristine (0.29) and dox (0.39) with PSC-833 at 1.0 microg/mL. Functional modulation of dox retention with PSC-833 was significantly associated with stage, but not with either the MTT assay or any of the monoclonal antibodies. None of the tests correlated with prior chlorambucil treatment. Correlation of dox retention with the monoclonal antibodies was mild to moderate and became stronger following chlorambucil treatment. Three patients who became resistant to VAD were found to express p-gp 170. We conclude that MDR can frequently be detected in patients with CLL. Furthermore, the expression of p-gp 170 increases with advancing stage, but not prior alkylating agent therapy. The functional expression of p-gp 170 increases with advancing stage and prior treatment and correlates well with monoclonal antibody detection (especially MRK-16). Patients who become resistant to VAD more frequently express p-gp 170 by a variety of techniques. PSC-833 is a more potent modulator of MDR than cyclosporin-A (CsA) ex vivo, and correlates better with stage of disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Iron release from human monocytes after erythrophagocytosis in vitro: an investigation in normal subjects and hereditary hemochromatosis patients.

This study investigated the release of erythrocyte-derived iron from purified human monocytes obtained from healthy volunteers and hereditary hemochromatosis (HH) patients. After erythrophagocytosis of 59Fe-labeled erythrocytes, a complete transfer of iron from hemoglobin (Hb) to ferritin was observed within 24 hours in both control and HH monocytes. The iron was released from the monocytes in the form of ferritin, Hb, and as nonprotein bound low molecular weight iron (LMW-Fe). During the initial rapid phase (<1.5 hours), iron release mostly consisted of Hb and LMW-Fe, while in the later phase (>1.5 hours), it was composed of ferritin and LMW-Fe. The kinetics of iron release were identical for HH monocytes. A high percentage of the total amount of iron was released as Hb both by viable normal and HH monocytes, suggesting that iron release as Hb is a physiologic process, which may occur whenever the erythrocyte-processing capacity of macrophages is exceeded. Most remarkably, HH monocytes released twice as much iron in a LMW form as control cells. Iron released in the form of LMW-Fe readily binds to plasma transferrin and may contribute to the high transferrin saturation and the occurrence of circulating nontransferrin-bound iron observed in HH patients.

Adult↗
PubMed1998

Adaptive response of iron absorption to anemia, increased erythropoiesis, iron deficiency, and iron loading in beta2-microglobulin knockout mice.

Recently, a novel gene of the major histocompatibility complex (MHC) class I family, HFE (HLA-H), has been found to be mutated in a large proportion of hereditary hemochromatosis (HH) patients. Further support for a causative role of HFE in this disease comes from the observation that beta2-microglobulin knockout (beta2m-/-) mice, that fail to express MHC class I products, develop iron overload. We have now used this animal model of HH to examine the capacity to adapt iron absorption in response to altered iron metabolism in the absence of beta2m-dependent molecule(s). Mucosal uptake, mucosal transfer and retention of iron were measured in control and beta2m-/- mice with altered iron metabolism. Mucosal uptake of Fe(III), but not of Fe(II), by the mutant mice was significantly higher when compared with B6 control mice. Mucosal transfer in the beta2m-/- mice was higher, independent of the iron form tested. No significant differences were found in iron absorption between control and beta2m-/- mice when anemia was induced either by repetitive bleeding or by hemolysis through phenylhydrazine treatment. However, iron absorption in mice made anemic by dietary deprivation of iron was significantly higher in the mutant mice. Furthermore, the beta2m-/- mice manifested an impaired capacity to downmodulate iron absorption when dietary or parenterally iron-loaded. The expression of the defect in iron absorption in the beta2m-/- mice is quantitative, with iron absorption being excessively high for the size of body iron stores. The higher iron absorption capacity in the beta2m-/- mice may involve the initial step of ferric mucosal uptake and the subsequent step of mucosal transfer of iron to the plasma.

Adaptation, Physiological↗
PubMed1998

Nerve function and oxidative stress in diabetic and vitamin E-deficient rats.

Nerve dysfunction in diabetes is associated with increased oxidative stress. Vitamin E depletion also leads to enhanced presence of reactive oxygen species (ROS). We compared systemic and endoneurial ROS activity and nerve conduction in vitamin E-depleted control and streptozotocin-diabetic rats (CE- and DE-), and in normally fed control and diabetic animals (CE+ and DE+). Nerve conduction was reduced in both diabetic groups. Vitamin E depletion caused a small further nerve conduction deficit in the diabetic, but not in the control animals. The combination of vitamin E deficiency and streptozotocin-diabetes (group DE-) appeared to be lethal. In the remaining groups, an important rise in sciatic nerve malondialdehyde (MDA) was observed in the vitamin E-depleted control rats. In contrast, plasma MDA levels were elevated in group DE+ only, whereas hydrogen peroxide levels were increased in group CE-. Endoneurial total and oxidized glutathione and catalase were predominantly elevated in group DE+. These data show that nerve lipid peroxidation induced by vitamin E depletion does not lead to reduced nerve conduction or changes in antioxidant concentrations as observed in STZ-diabetes. The marked systemic changes in MDA and antioxidants suggest that nerve dysfunction in experimental hyperglycemia is rather a consequence of systemic than direct nerve damage.

Animals↗
PubMed1998

Electrophysiological brain stem investigations in idiopathic narcolepsy.

Narcolepsy is associated with various rapid eye movement (REM) sleep abnormalities. Distinct brain stem areas seem to play a prominent role in REM sleep regulation. Recent magnetic resonance imaging (MRI) studies have led to conflicting findings concerning the presence of structural brain stem lesions in patients with idiopathic narcoleptic syndrome. However, multimodal electrophysiological brain stem investigations may reveal functional brain stem abnormalities even in the absence of MRI abnormality. Therefore we investigated brain stem function in 12 idiopathic narcoleptic patients by systematically studying tegmental brain stem pathways. All of the patients met the diagnostic criteria of the International Classification of Sleep Disorders, with typical changes in polysomnography and the multiple sleep latency test. Electrophysiological investigations comprised masseter reflex, blink reflex, masseter inhibitory reflex, early auditory evoked potentials and electrooculography with vestibular testing. In no patient were electrophysiological brain stem abnormalities observed. Our findings do not support the existence of a relevant brain stem lesion in narcoleptic patients with normal neurological status.

Adult↗
PubMed1998

Iron metabolism and erythropoiesis after surgery.

BACKGROUND: This was a prospective study comparing the effect of major and minor surgery on haematological variables concerning erythropoiesis, iron metabolism and acute-phase response proteins. METHODS: Thirty-one otherwise healthy patients, 15 having major orthopaedic surgery and 16 undergoing minor surgery, were studied. Blood samples were taken before surgery and 1, 4, 10 and 28 days after operation. RESULTS: Haemoglobin concentration was decreased for up to 4 weeks after surgery. Serum erythropoietin concentration and reticulocyte count were raised after major surgery only. Serum iron concentration dropped the day after major (to 23 per cent of its preoperative level) and minor (to 46 per cent of its preoperative level) surgery and remained lower for up to 28 days after major surgery. Serum transferrin concentration and transferrin saturation decreased after both types of surgery while ferritin concentration increased. Serum transferrin receptor concentration increased only 4 weeks after major surgery (P < 0.01). The interleukin 6 peak (day 1) was greater after major than minor surgery, as was the C-reactive protein peak (day 4). CONCLUSION: Both major and minor surgery induce a state of hypoferraemia in the presence of adequate iron stores. The degree of this transient form of 'anaemia of chronic disease' is related to the extent of surgery. Iron supplementation in the first weeks after surgery (if iron stores were normal before operation) is ineffective.

Acute-Phase Proteins↗
PubMed1998

A functional defect in hereditary haemochromatosis monocytes and monocyte-derived macrophages.

BACKGROUND: Hereditary haemochromatosis (HH) is a disease of the metabolism of iron characterized by increased iron absorption and heavy parenchymal iron deposition, but with the presence of little iron in the mononuclear phagocytic system (MPS). METHODS: To investigate the role of the MPS, the phagocytic ability of HH monocytes (MNs) and in vitro monocyte-derived macrophages (MDMs) was studied. HH patients with different degrees of iron accumulation were chosen. RESULTS: We observed that HH patients' MNs and MDMs have a significantly decreased ability to phagocytose rabbit red blood cells (RRBCs) and that HH MNs possess a significantly decreased capacity to phagocytose Staphylococcus aureus (S. aureus). The decrease in the ability to phagocytose S. aureus, however, was kinetic in nature, explaining the absence of increased prevalence of bacterial infections among HH patients. Both RRBCs and S. aureus were preopsonized with heat-inactivated serum. No alteration in the complement-dependent phagocytosis of Cryptococcus neoformans was demonstrated when normal human serum was used. The phagocytosis defect was observed in 100% of HH patients and was independent of the magnitude of iron overload, age or liver damage, and affected the antibody-mediated uptake of bacteria and (R)RBCs.

Adult↗
PubMed1998

Organic dust exposures from work in dairy barns.

Environmental surveys were conducted in 85 barns, predominantly dairy, in central Wisconsin to characterize exposures to organic dusts and dust constituents from routine barn work. Environmental analytes included airborne dusts (total, inhalable inlet, and respirable), particle size distributions, endotoxins, total spore and bacteria counts, viable bacteria and fungi, histamine, cow urine antigen, mite antigen, ammonia, carbon dioxide, and hydrogen sulfide. The geometric mean (GM) concentration of airborne dusts include area total, 0.74 mg/m3; personal inhalable inlet, 1.78 mg/m3, and area respirable, 0.07 mg/m3. Viable bacteria and fungi, spores, endotoxins, histamine, cow urine antigen, and mite antigen were quantifiable constituents of these organic dusts and potential respiratory exposure hazards from routine dairy barn work. Endotoxin concentrations from the inhalable inlet samples ranged from 25.4 endotoxin units per cubic meter of air (EU/m3) to 34,800 EU/m3. The GM endotoxin concentration from these samples, 647 EU/m3, exceeds estimated threshold exposure levels for respiratory health effects. Ammonia was a common irritant quantified in most dairy barns. There were significant correlations between the concentrations of organic dusts and certain dust constituents, although in most instances these correlations were not strong. These sampling results demonstrate the complex nature of organic dusts and provide quantitative description of the exposures to toxic and immunogenic dust constituents during routine barn work.

Air Microbiology↗
PubMed1998

Iron absorption in erythropoietin-treated haemodialysis patients: effects of iron availability, inflammation and aluminium.

BACKGROUND: The response to recombinant human erythropoietin (rHuEpo) is determined primarily by the availability of iron. In contrast to i.v., iron, oral iron supplementation is often insufficient for an optimal response. METHOD: We studied iron absorption and the effects of iron status, aluminium status and inflammation in 19 chronic haemodialysis patients on maintenance rHuEpo therapy. Iron mucosal uptake after 24 h, iron retention after 2 weeks and mucosal transfer of iron were determined with a whole-body counter using an oral dose 59Fe. Iron absorption was measured once without, and once after the ingestion of 2 g aluminium hydroxide. RESULTS: On the basis of transferrin saturation, two groups of dialysis patients were distinguished: a group with a functional iron deficiency (n = 9), and an iron-replete group (n = 10). In the iron-deficient dialysis patients group, mucosal uptake, mucosal transfer, and iron retention were 49.9% +/- 29.4, 0.73 +/- 0.29, and 41.6% +/- 32.2, being significantly lower than in a non-uraemic iron deficient population (P < 0.01, P < 0.05, P < 0.01 respectively). In the iron-replete dialysis patients group, mucosal uptake, mucosal transfer, and iron retention were 20.0 +/- 12.3, 0.59 +/- 0.18, and 11.1 +/- 6.7, mucosal uptake and iron retention being lower than in a normal iron-replete population (P < 0.0005 and P < 0.003 respectively). Dialysis patients with high C-reactive protein (CRP) values showed lower iron absorption. Iron absorption data correlated significantly with transferrin saturation and CRP in the iron-deficient group, and with serum ferritin in the iron-replete group. Iron absorption decreased after an aluminium hydroxide challenge in the iron-deficient patients to the lower levels of the iron-replete subjects. Body aluminium stores, estimated by the desferrioxamine test, did not correlate with parameters of iron absorption. CONCLUSION: The absorption of iron in dialysis patients is decreased in haemodialysis patients, which may, at least in part, be due to inflammation. Aluminium ingestion further reduces absorption in functional iron-deficient patients.

Absorption↗
PubMed1998

The absorption of iron is disturbed in recombinant human erythropoietin-treated peritoneal dialysis patients.

BACKGROUND: Intravenous iron supplementation is often necessary in recombinant human erythropoietin (r-HuEPO)-treated haemodialysis (HD) patients, but rarely in r-HuEPO-treated peritoneal dialysis (PD) patients. This may be due to differences in iron absorption or blood loss. METHOD: Iron absorption (whole-body counting after ingestion of a radiolabelled iron test dose) and iron metabolism were compared in eight iron-replete rHuEPO-treated PD patients (serum ferritin 100-500 microg/l) and 68 healthy iron-replete controls (sufficient iron in bone marrow specimen). RESULTS: Mucosal uptake (13.4+/-9.8%), mucosal transfer (0.34+/-0.18) and iron retention (4.9+/-4.0) in PD patients was significantly lower than in controls (42.9+/-18.8%, P < 0.0001, 0.63+/-0.18, P < 0.0001, and 28.0+/-16.7%, P<0.0001). CONCLUSION: Iron absorption is impaired in PD patients, as we have shown previously for HD patients. One reason for higher iron needs in HD patients may be higher blood losses due to the dialysis procedure and blood sampling for laboratory tests.

Absorption↗
PubMed1998

59Fe labelling of rabbit erythrocytes as a continuous source for iron metabolism studies.

The study of iron metabolism in human phagocytes requires a continuous source of 59Fe-labelled erythrocytes with high specific activity. Previously, rats and mice have been used for this purpose, but only limited amounts of blood can be obtained and the animals are (often) sacrificed during the experiment. This paper describes the development of a rabbit model for use as a continuous source of highly labelled erythrocytes as an alternative to mice and rats. A chinchilla rabbit was serially injected with 59Fe citrate to maintain a level of labelling of 12 x 10(5) cpm/ml of blood. During the 42-month use of the chinchilla rabbit, a total of 190 MBq was injected and a total of 277 ml blood was withdrawn. During the whole period, the health of the animal was not affected and no important changes were found in any of the haematological parameters studied. The protocol was successfully applied with a second rabbit with the same results. Our model provides a simple continuous source of highly labelled erythrocytes, minimizing the number of animals otherwise needed for this type of experiment.

Animals↗
PubMed1997

Iron deficiency in developed countries: prevalence, influence of lifestyle factors and hazards of prevention.

OBJECTIVE: To review the prevalence of iron deficiency in developed countries, the influence of lifestyle factors that may contribute to its occurrence, and dangers of population directed prevention. DESIGN: Relevant literature was selected to identify populations at risk for iron deficiency and iron overload. RESULTS: Although iron deficiency anaemia is not a major health problem in developed countries, specific groups of the population remain endangered. These groups are young children, adolescents, pregnant women, the elderly, blood donors, vegetarians, endurance athletes and migrants. On the other hand, about 10% of Caucasians carry the mutation for hereditary haemochromatosis and are at risk for iron overload. CONCLUSION: Measures to prevent iron deficiency should be specifically aimed at population groups at risk. Actions to increase iron intake and bioavailability in the general population can be harmful for subjects with homozygous and heterozygous forms of iron overload diseases.

Adolescent↗
PubMed1997

Evaluation of the role of Fc gamma and complement receptors in the decreased phagocytosis of hereditary haemochromatosis patients.

Hereditary haemochromatosis (HH) monocytes have a decreased antibody mediated phagocytosis of rabbit erythrocytes and Staphylococcus aureus compared to control monocytes. In order to investigate whether this decrease could be attributed to a different level of expression of Fc gamma receptors (Fc gamma R) or complement receptors (CR), which cooperate even in the absence of complement, the surface expression of these receptors was determined on monocyte-enriched suspensions. In contrast to what was expected, HH monocytes displayed a significantly higher level of Fc gamma RI and Fc gamma RIIa as compared to healthy donor monocytes, but these differences were very small. The expression of the other receptors studied were similar for both groups. The heat-inactivated mouse serum used for opsonizing the erythrocytes mainly contained mouse IgG1. Two genetically different forms of Fc gamma RIIa are known, each with a different affinity for mouse IgG1 antibodies. Therefore, the Fc gamma RIIa polymorphism in monocytes (MN) of both groups was also investigated. A similar distribution was found for patients and healthy donors. In addition, the extent of erythrophagocytosis of both donors and patients was independent of Fc gamma RIIa allotype. Our results indicate that the altered phagocytosis by HH monocytes cannot be attributed to a different level of expression of receptors involved in phagocytosis or to Fc gamma RIIa polymorphism.

Adult↗
PubMed1997

Dietary ascorbic acid raises iron absorption in anaemic rats through enhancing mucosal iron uptake independent of iron solubility in the digesta.

We studied Fe absorption from FeSO4 in rats with Fe deficiency-induced anaemia that were given an Fe-sufficient purified diet without or with ascorbic acid (10.4 g/kg diet). Attention was focused on mucosal Fe uptake as measured in vivo by a double-isotope technique. Haemoglobin repletion and liver Fe levels were not affected when the ascorbic acid-supplemented diet was given, but apparent Fe absorption and retention of orally administered 59Fe were significantly enhanced. The distribution of Fe between liquid and solid phases of contents of both the stomach and the proximal intestine was not affected by the feeding of the ascorbic acid, but ascorbic acid significantly enhanced mucosal Fe uptake. It is concluded that ascorbic acid in the diet raises mucosal Fe uptake through a mechanism independent of the intestinal Fe solubility.

Anemia↗