Search PubMed⌕ Search

Biomedical subjects

M de Sousa

Publications and source records attributed to M de Sousa.

At least 55 records · Page 3Linked to original sources
PubMed1992

Importance of establishing appropriate local reference values for the screening of hemochromatosis: a study of three different control populations and 136 hemochromatosis family members. Hemochromatosis Clinical and Research Group.

Hemochromatosis is a human leukocyte antigen-linked (HLA-linked), potentially lethal disorder of iron metabolism with a high prevalence in white populations albeit an autosomal recessive mode of transmission. The diagnosis and treatment at early stages of the disease are critical to the prevention of the morbidity and mortality caused by the iron overload. After the identification of the first cases of hemochromatosis in Portugal, a screening program was started with a systematic search for the disease among family members of the patients, as well as in subjects from the normal population. In this study we analyze the results obtained with a total of 136 family members from 15 different families and 353 control subjects from three different villages, two in the north and one in the south of Portugal. We establish reference values for the biochemical tests used in the screening for iron overload and analyze the factors that affect those results. Besides sex-related differences, factors that were found to influence biochemical parameters most significantly included age and levels of daily alcohol intake. In addition, differences in iron status were identified between the populations from the regions in the north and the south of the country. We estimate, by HLA typing and family studies, a gene frequency for hemochromatosis of 0.14 that corresponds to a frequency of homozygotes and heterozygotes of 0.019 and 0.24, respectively.

Adolescent↗
PubMed1992

[Renal cell carcinoma and Reiter's syndrome].

A case of a prolonged febrile syndrome in a 41-year old man is presented. A renal tumor and a seronegative spondylitis associated with a Reiter's syndrome were disclosed together. The authors did not find any reference to an eventual relation between these two diseases.

Adult↗
PubMed1991

Recognition of self within self: specific lymphocyte positioning and the extracellular matrix.

In this article, Maria de Sousa and colleagues address the importance of interactions between lymphocytes and extracellular matrix components to lymphocyte migration and positioning, emphasizing the role of the basement membrane and the complex stromal matrix of the lymphoid organs. They conclude that such interactions are of great importance, both in the physiological functioning of the immune system and in organ transplantation.

Animals↗
PubMed1991

Stability of CD4/CD8 ratios in man: new correlation between CD4/CD8 profiles and iron overload in idiopathic haemochromatosis patients.

The proportions of CD4+, CD8+ cells were determined in peripheral blood samples obtained from 27 patients with idiopathic haemochromatosis and 67 healthy controls. Samples from the patients were obtained at the start of therapy and at intervals during intensive phlebotomy treatment in which 400 ml of blood are removed each week for 6 months to 2 years. Patients varied in their CD4/CD8 ratios from 0.8 to 4.2. An individual's CD4/CD8 ratio, however, remained unaffected by the repeated removal of large volumes of blood by phlebotomy confirming the existence of a homeostatic regulation of the relative numbers of the two major peripheral T cell pools in man. Follow-up of iron reentry into the transferrin pool at the end of the intensive phlebotomy treatment indicates that the relative proportion of circulating CD4/CD8 cells is critically related to the regulation of iron absorption.

Adult↗
PubMed1990

Differential effects of eight metal ions on lymphocyte differentiation antigens in vitro.

In vitro studies were conducted to determine the effects of metal ions known to be released from metallic implants in vivo on the expression of lymphocyte surface antigens. Normal human peripheral blood lymphocytes were exposed to various concentrations of metal ions (Fe3+, Ni2+, Co2+, Mo6+, V5+, Cr6+, Cr3+, and Ti3+) for 30 min at 37 degrees C in a 5% CO2 atmosphere, and then analyzed for their ability to form rosettes with sheep red blood cells. Following this preliminary analysis, lymphocytes were exposed to the metal ions found to inhibit the E-rosette reaction (Fe3+, Ni2+, and Co2+) in order to determine which of the following surface antigens were affected: CD2, CD3, CD4, CD8, CD1, CD22, CD10, and HLA-DR. Our results showed that the in vitro treatment of lymphocytes with Fe3+ or Co2+ caused inhibition of CD2 only, whereas Ni2+ caused inhibition of both CD2 and CD3 antigens. These findings suggest that Fe3+, Co2+, and Ni2+ ions may interfere with T cell activation since both CD2 and CD3 are involved in that process.

Antigens, CD↗
PubMed1990

Method for establishing serum ferritin reference values depending on sex and age.

A method is described for the establishment of reference values for serum ferritin depending on sex and age. The results obtained in a stratified random sample of 353 healthy individuals from the Portuguese population revealed that 23% of the variation observed on serum ferritin values was related to sex differences and 6% of the variation was explained by age differences. Furthermore, the effect of age was different in both sexes: serum ferritin values increase with age in females over 40 years and in males under 40. The minimum and maximum reference values were established for the different subgroups of subjects as follows: for females under 40 years and males over 40, reference values were considered as the 2.5 and 97.5 percentiles from the adjusted lognormal distribution; for females over 40 years and males under 40, reference values were considered as the exponential transformation of the upper and lower limits of the 95% prediction intervals for the log of serum ferritin for each particular age point.

Adolescent↗
PubMed1989

Collagen arthritis in the rat is initiated by CD4+ T cells and can be amplified by iron.

The role of iron in arthritis was studied by administering ferric citrate (Fe-cit) to age-matched, female Sprague-Dawley rats immunized with chick type II collagen on Day 0. Rats received intravenously (iv) either Fe-cit (7.7 mg/kg body wt) or an identical concentration of sodium citrate on varying days after immunization. Transferrin saturation peaked (88-95%) 1 hr post-Fe-cit and returned to baseline values within 24 hr. Injection of Fe-cit on either Day 3 or Day 5, but not on Day 7 or Day 9, significantly (P less than 0.03) increased the incidence of arthritis. Synovium from the infrapatellar fat pad was harvested on Days 0-10 for analysis by immunocytochemistry. The inceptual morphologic change in the synovium following collagen immunization in rats not injected iv was an increase in the number of CD4+ and transferrin receptor+ mononuclear cells in perivascular regions; compared to Day 0 both cell types had increased two- to threefold by Day 3. On Day 7, an increase in CD8+ mononuclear cells occurred and the first polymorphonuclear leukocytes were noted. These alterations resulted in a peak in the CD4-CD8 ratio on Day 3, with a gradual decline thereafter. Although Fe-cit administration promoted the ingress of these mononuclear cells, it did not change the CD4-CD8 ratio significantly or recruit polymorphonuclear leukocytes into the joint tissue. Serum antibody titers to type II collagen, measured 20 days after immunization by an enzyme-linked immunosorbent assay, and delayed-type hypersensitivity to collagen, measured by a radiometric ear assay on Day 23, did not differ significantly between the groups. As well as showing that the initial intrasynovial event in collagen arthritis is perivascular infiltration by members of the CD4+ T cell subset displaying a phenotypic sign of activation, these findings demonstrate that iron administered at a critical time after immunization enhances the induction of collagen arthritis. The coincidence of this brief period of susceptibility with maximum CD4-CD8 ratios within the synovium and its occurrence prior to the stage of neutrophil infiltration are consistent with the possibility that the augmenting effect of iron is mediated by the inducer T cell subset.

Animals↗
PubMed1989

Modulation of immune responses in mice by oral administration of niflumic acid.

The in vivo effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the host immune system are still poorly understood. However, through inhibition of prostaglandin synthesis, NSAIDs may exhibit immunomodulating properties. The present work was aimed at evaluating the influence of niflumic acid on immune responses when administered orally for 7 consecutive days to 8-week-old inbred mice. Immunological tests were performed 24 h after the arrest of the treatment. At a dosage of 50 mg/kg/day, niflumic acid exerted noticeable immunostimulating effects, as shown by an increase in plaque-forming cell numbers after in vivo immunization with sheep red blood cells, an augmentation of spleen cell proliferation responses to stimulation with T- or B-cell mitogens and of T-cell cytotoxic response to allogenic cells. Phagocytosis-induced chemiluminescence of peritoneal macrophages was also enhanced whereas interleukin-1 production by these cells was depressed, but without concomitant modification in interleukin-2 production by T-cells. Increasing the niflumic acid dosage to 75 mg/kg resulted in the disappearance of the immunostimulatory effects on lymphocytes responses. Macrophage activities were affected similarly in mice receiving 50 mg/kg. These results demonstrate that niflumic acid is able to stimulate in vivo several immunological functions and, consequently, to maintain host immune defenses. Interestingly, it depressed interleukin-1 production, known to play a major role in the inflammatory process.

Administration, Oral↗
PubMed1989

Immune cell functions in iron overload.

A number of studies done in the last 10 years demonstrate the importance of iron in regulating the expression of T lymphoid cell surface markers, in influencing the expansion of different T cell subsets and in affecting different immune cell functions in vitro. It has been argued that some of the results obtained could be explained by the formation of iron polymers in the experimental conditions used in vitro (Soyano Fernandez & Romano, 1985). In this review the results of studies of immunological function in clinical situations of iron overload are analysed. From this analysis, it is concluded that the majority of the observations made in vitro have a counterpart in vivo, thus providing additional compelling evidence for the importance of iron as an immunoregulator.

Hemochromatosis↗
PubMed1988

Activation of rat synovium by iron.

We observed a consistent sequence of activation changes in rat knee synovia following a single intravenous injection of sterile ferric citrate at a dosage sufficient to cause a transient saturation of transferrin. The initial alteration, appreciated 2 hours postinjection, consisted of an expansion in the lumen of synovial lining and subsynovial tissue due to the hypervascularity and increased cellularity was noted, along with peaks in the mitotic activity of synovial cells (fourfold over baseline) and pinocytosis by endothelial cells. During the period of 8-24 hours, mature collagen appeared in the space between pericyte layers and between pericytes and endothelial cells, and 2-9-fold increases in ferritin +, W3/13+, W3/25+, Ox8+, and Ox26+ mononuclear cells occurred. In contrast to the action on synovial fibroblasts, iron injection did not affect the mitotic activity of fibroblasts within the serosa of the small intestine. These findings demonstrate that, under experimental conditions, iron can readily induce changes in the synovium that are reminiscent of early events occurring in response to antigen.

Animals↗
PubMed1988

Iron exerts a specific inhibitory effect on CD2 expression of human PBL.

The effect of in vitro exposure to ferric citrate (Fe-citrate) on the expression of human lymphocyte surface markers was studied. The following markers were examined: E-rosette formation, CD2, CD3, CD4, CD8, CD1, CD22, CD10 and HLA-DR. Pretreatment of peripheral blood lymphocytes (PBL) with Fe-citrate at concentrations ranging from 10(-2) M to 10(-5) M resulted in the exclusive inhibition of E-rosette formation and CD2 expression. None of the other surface antigens examined appeared to be sensitive to the Fe-citrate treatment. Competition experiments further indicated that iron interacts specifically with CD2 on T lymphocytes.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Evaluation of indium-111 chloride as a radiopharmaceutical for joint imaging in a rabbit model of arthritis.

The potential use of 111In-chloride as a radiopharmaceutical for quantitating the extent of synovitis was investigated in a rabbit model of antigen-induced arthritis. Rabbits with monoarticular disease were injected with 111In-chloride and imaged at 30 minutes and 24, 48, 72, and 96 hours. In control knee joints, the ratio of activity in the knee to a soft-tissue region in the thigh remained constant (1.5-1.85:1); in arthritic knees, the 111In uptake ratio increased from 2:1 to 3.2, 3.5, 3.9, and 4.6:1 at the later time points. The difference between the knee-to-soft-tissue ratios observed in the control and involved joints was significant (P less than .01, 48-96 hr). Tissue distribution measurements demonstrated that the synovium and intra-articular structures covered by synovium in arthritic joints had the highest concentration of 111In. In control joints, these tissues were found to take up tenfold less activity. Good correlation was observed between the 111In knee-to-soft-tissue ratios calculated from the images and histologic assessment of the severity of synovitis.

Animals↗
PubMed1987

Association of serum iron, serum transferrin saturation, and serum ferritin with survival in acute lymphocytic leukemia.

The present investigation was motivated from the consideration that a host environment rich in iron, represented by high serum transferrin saturation (TS) and high serum iron and serum ferritin levels might offer favorable growth conditions for leukemic cells in addition to infection, thus affecting survival. Serum measurements were obtained on 113 pediatric patients with acute lymphoblastic leukemia (ALL), seen at Memorial Sloan-Kettering Cancer Center between May 20, 1981 and August 8, 1983. A significant difference (p less than 0.001) was found between the survival of patients according to whether their first measured TS was greater than 36% or less than 36%, with fewer deaths in the group with TS less than 36. The relationship between TS and survival was still observed when patients were stratified according to length of time from diagnosis, risk group, French-American-British (FAB) classification, or presence of organomegaly at diagnosis (p less than 0.001). Similar differences were observed between survival of patients grouped according to their first measured serum ferritin. These results independently confirm and extend observations presented earlier and support the consideration that motivated this study. The value of serum iron-related measurements as prognostic variables cannot be established from this type of study; however, these findings suggest the need for a prospective study.

Child↗
PubMed1986

Decreased natural killer activity in thalassemia major: a possible consequence of iron overload.

We have investigated the natural killer (NK) activity of both fractionated (Percoll density gradient) and unfractionated mononuclear cells from patients with beta-thalassemia major who are iron overloaded as a consequence of chronic transfusion therapy. These patients were found to have significantly decreased NK activity against K562 targets at all effector:target ratios tested (p less than 0.001). Both splenectomized and nonsplenectomized patients had normal proportions of Leu-11b-staining (NK) cells. Since they had normal to elevated absolute white cell and lymphocyte counts, a change in the absolute number of NK cells could not account for the decreased killing. We also found that the decrease in NK activity was transfusion related (r = -0.603, p less than 0.005). To determine whether or not this decrease in NK activity could be related to iron overload, we preincubated patient effector cells with desferrioxamine (DFO) or 2,3-dihydroxybenzoic acid (DHB) for 6 hr before addition of K562 targets. Both of these iron-chelating agents consistently increased the NK activity of cells from thalassemia patients. DHB had the greater effect, being able to increase patient NK activity to virtually normal levels. On the other hand, preincubation of cells from normal controls with DHB caused only a slight increase in NK activity, while similar treatment with DFO had little or no effect. When target cells were preincubated with the chelating agents before addition of either normal or patient effector cells, no change in cytotoxicity was seen, demonstrating that the chelating agents act at the effector cell level. Furthermore, if the chelating agents were saturated with iron prior to preincubation with the effectors, no increase in the cytotoxicity of thalassemic NK cells was observed. These results indicate that thalassemia patients have a reversible, transfusion-related decrease in NK function which may arise as a consequence of iron overload.

Cell Separation↗