[Screening for hemoglobinopathy].
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Denmark↗
Biomedical subjects
H S Birgens
Publications and source records attributed to H S Birgens.
[Hemoglobinopathy in the county of Copenhagen].
In Copenhagen County, haemoglobinopathy was centralized to the Department of Haematology L, Herlev University Hospital from January 1995. All pregnant women of relevant ethnic origin admitted to the obstetric departments of the Country in 1995, were examined by haemoglobin electrophoresis. furthermore, we performed haemoglobin electrophoresis on immigrants admitted on suspicion of haemoglobinopathy. 24 (4.8%) of 505 examinations in pregnant women were abnormal. 12 reflected a carrier condition for either beta-thalassaemia or sickle cell disease; 53 of 82 examinations in non-pregnant patients were abnormal; 29 had beta-thalassaemia minor and the rest included the haemoglobin variants C, D, E, H and S, mostly in a heterozygous from. The genetic lesions, all of which were mutations, were characterized by molecular genetic analysis in 13 cases with demonstrated beta-gene disorder. The gene frequency of haemoglobinopathies among immigrants to Denmark is common. The Danish health care system must therefore be prepared to address this problem including the clinical aspects, screening and molecular biological examinations, prenatal diagnosis and genetic counselling.
Adult↗
[Protein structure and pathology of the erythrocyte membrane].
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Erythrocyte Deformability↗
[Hemoglobinopathies. Current therapeutic possibilities].
In recent years, the number of immigrants has increased considerably in Denmark. Consequently, a series of new clinical pictures has appeared in the Danish health care system. Typical examples are the genetic diseases, the haemoglobinopathies. Most of the immigrants come from areas, where the gene frequency of these disorders is widely distributed, for instance the Mediterranean countries, the Middle East, Southeast Asia and Africa. Most frequent are the heterozygous thalassaemias, but also the number of patients with severe thalassaemia and other clinically important haemoglobinopathies such as sickle cell anaemia has also increased in recent years. The clinical problems concerning these patients focus on two important topics, namely genetic counselling of heterozygous individuals (in some cases combined with prenatal diagnostics) and the treatment of patients with clinically severe haemoglobinopathy. The only curative treatment of the haemoglobinopathies is allogeneic bone marrow transplantation, but this treatment can only be offered to a few of these patients. However, a variety of therapeutic options exist which can improve their prognosis and quality of life. Since the number of patients with these diseases will probably increase over the next years we find it relevant, based on typical case stories, to give a review of the present therapeutic possibilities for these disorders.
Adult↗
[Anemia in chronic disease].
Anaemia of chronic disease is that associated with inflammatory disorders such as prolonged infections, auto-immune diseases and some cancers. The pathogenesis of anaemia of chronic disease is complex and includes a reduced erythropoiesis, slightly shortened red cell survival, and changes in the iron metabolism. New experimental data have shown that cytokines released during the inflammatory process are of crucial importance in this context. In particular interleukin-1 and tumor necrosis factor alpha, released from activated macrophages, have been shown to inhibit erythropoiesis and might initiate changes in iron metabolism. Clinically, anaemia of chronic disease is mild and the underlying disease usually dominates the clinical picture. Most often, the anaemia takes the form of a normocytic, normochromic anaemia with low serum iron although the iron stores are normal or increased. Anaemia of chronic disease should be distinguished from anaemia due to iron deficiency, and at the moment measurement of serum ferritin seems to be the best analysis for this purpose.
Anemia↗
The monocytic receptor for lactoferrin and its involvement in lactoferrin-mediated iron transport.
Several studies suggest biological functions of the iron-binding neutrophilic glycoprotein lactoferrin that imply an initial interaction with cells from the monocyte/macrophage family. Among these, an important role of lactoferrin as responsible for the inflammatory-induced blood hyposideremia and accumulation of iron in the monocyte/macrophage system has been suggested mainly based on experiments in rodents. In a series of experiments we have examined the binding of human lactoferrin to human monocytes. We have demonstrated the presence of a receptor binding including a high-affinity component and a low-affinity component. The affinity of the binding is compatible with a biological significance of this receptor (KD is about 10(-8) M, and the number of receptors about 10(6) per cell). More than 90% of the lactoferrin will dissociate from the cell. The binding is not truly reversible since lactoferrin will lose its receptor-binding property after dissociation from the cell. The only observed change in the molecule is a small decrease in isoelectric point from 8.9 to 8.8. Lactoferrin is able to translocate at least 50% of its bound iron to intracellular ferritin in monocytes. These findings are compatible with the idea that lactoferrin might be involved in the pathogenesis of the disturbances in iron metabolism observed during inflammation.
Biological Transport↗
Reversible adult-onset cyclic haematopoiesis with a cycle length of 100 days.
Cyclic neutropenia is the most frequent of the cyclic haematopoietic disorders characterized by its regular 21 d cyclic fluctuations in the number of blood neutrophils, and in many cases simultaneous fluctuations in the other blood cell lines. In this paper we describe a 77-year-old woman with a cyclic pancytopenia including all the myeloid cell lines and to some extent the lymphocytes with a constant and predictable oscillation period of about 100 d. Serial bone marrow biopsies and plasma lactoferrin measurements indicated a similar fluctuating pattern in the bone marrow production of neutrophils. Serial measurements of plasma GM-CSF concentration pointed at a simple feed-back inhibitory system. The condition was present for at least 4 years, after which it gradually improved, although the thrombocyte count still showed a fluctuating tendency after a further 4 years of observation. The clinical consequences were mild symptoms of anaemia and a few episodes of respiratory infections occurring during pancytopenic periods. We think this is the first case described in the literature with this variant of a cyclic haematopoietic disorder. The precise pathophysiological mechanism behind this condition is obscure, but probably it is due to a regulatory disturbance at a very early step in the haematopoietic stem cell hierarchy.
Aged↗
[Metabolic disorders in the treatment of malignant hematologic diseases--the acute tumor lysis syndrome].
The acute tumor-lysis syndrome is a potentially fatal complication which characteristically arises during initial chemotherapy of malignant hematological diseases with large tumor burdens. The syndrome is characterized by hyperphosphatemia, hypocalcemia, hyperuricemia and often acute renal failure. Prior to chemotherapy the patient should be treated for 12-24 hour with intensified diuresis to ensure optimal renal function. The treatment of the fully developed syndrome is hemodialysis. Three cases of TLS which developed during initial chemotherapy of patients with acute lymnphoblastic leukemia and non-Hodgkin lymphoma are presented.
Acute Disease↗
The interaction of lactoferrin with human monocytes.
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Humans↗
[The cryopathies].
The term cryopathies includes conditions in which abnormal sensitivity to cold is a prominent feature and includes the cold agglutinin syndrome, the cold hemolysin syndrome, the cold urticarias, the cryoglobulinemias, and cryofibrinogenemia. The cryopathies may be secondary to lymphoproliferative, autoimmune, and infectious diseases, but in many patients no underlying disease can be found (essential cryopathy). Avoidance of cold is of prime importance in all patients. Underlying disease should be treated, if possible. Severe therapeutic problems may arise in patients with essential cryopathies.
Adult↗
Impaired receptor binding and decrease in isoelectric point of lactoferrin after interaction with human monocytes.
The iron-binding glycoprotein lactoferrin binds to specific receptors on human monocytes as an initial step implicated in monocytic iron deposition. In this study, the properties of lactoferrin were studied after its interaction with human monocytes. Rebinding of lactoferrin to its monocytic receptor was grossly impaired and a small decrease in isoelectric point from 8.9 to 8.8 was observed. In contrast, antigenic and iron-binding properties of lactoferrin were preserved, the molecular weight by SDS-polyacrylamide gel electrophoresis was unchanged and no low-molecular fragments were detected by gel-filtration. These findings indicate that lactoferrin molecules cannot operate in a cyclic manner to deposit iron. Furthermore, these results might contribute towards explaining the complex disappearance kinetics observed for lactoferrin in plasma.
Chromatography, Gel↗
Identification of a highly mobilizable subset of human neutrophil intracellular vesicles that contains tetranectin and latent alkaline phosphatase.
Tetranectin, a protein recently identified in a wide variety of human secretory cells (Christensen, L., and I. Clemmensen. 1989. Histochemistry. 92:29-35) was found to colocalize with latent alkaline phosphatase activity in fractions well separated from azurophil granules, specific granules, gelatinase-containing granules, and plasma membranes when postnuclear supernatants of nitrogen-cavitated neutrophils were fractionated on discontinuous Percoll density gradients. Stimulation of intact neutrophils with nanomolar concentrations of FMLP, leukotriene B4, 10-100 U/ml of tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor resulted in parallel release of tetranectin and translocation of alkaline phosphatase to the plasma membrane. Furthermore, intracellular pools of tetranectin and latent alkaline phosphatase were completely released from neutrophils under conditions that barely induced release of specific granules containing B12-binding protein. These findings indicate that tetranectin and latent alkaline phosphatase define an easily mobilizable population of cytoplasmic storage organelles in human neutrophils which are functionally distinguishable from azurophil, specific, and gelatinase-containing granules. These organelles may play an important role as stores of membrane proteins that are mobilized to the cell surface during stimulation by inflammatory mediators.
Alkaline Phosphatase↗
Lactoferrin-mediated transfer of iron to intracellular ferritin in human monocytes.
Interactions of 125I-59Fe-lactoferrin with human monocytes were studied. After 4 hours of incubation, the uptake of 59Fe exceeded that of 125I. In dissociation studies the cellular 59Fe-activity was only partly dissociable during 16 h, whereas the 125I-activity could be released nearly completely. Disruption of the cells and studies on the cytosolic phase were performed employing gel-filtration and affinity chromatography. An appreciable amount of lactoferrin was found in the cytosolic phase. About 50% of the cytosolic 59Fe-activity was bound to ferritin. The results suggest that lactoferrin is internalized into monocytes and that iron is transferred to ferritin. These cellular events may contribute to an understanding of the accumulation of iron in the monocyte/macrophage system observed during inflammatory conditions.
Cells, Cultured↗
[Neutrophilic granulocytes. Myelopoiesis, kinetics and function].
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Bone Marrow↗
[Thrombotic thrombocytopenic purpura. Treatment with anti-thrombocyte drugs].
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Aged↗
Measurement of beta-2-microglobulin in serum and plasma by an enzyme-linked immunosorbent assay (ELISA).
A simple technique for the measurement of beta-2-microglobulin (beta 2M) in serum was developed. The method was designed as a sandwich technique using rabbit anti-human antibodies, employing commercially available reagents in an enzyme linked immunosorbent assay (ELISA). The assay was of high specificity, sensitivity, accuracy and reproducibility. beta 2M in serum was strongly correlated with age (p less than 0.005), but independent of sex. Values in heparin and citrate plasma were significantly lower than in serum (p less than 0.001), whereas values in serum and EDTA plasma were similar. Release of beta 2M from normal blood cells was not observed in vitro before the test procedure. An excellent correlation between the results obtained in the ELISA and a RIA was demonstrated (rS = 0.99, p less than 0.0001).
Adolescent↗
Ultrasonic demonstration of clinical and subclinical hepatic venous thrombosis in paroxysmal nocturnal haemoglobinuria.
Extensive hepatic venous thrombosis was demonstrated by ultrasonic scanning in three patients with paroxysmal nocturnal haemoglobinuria (PNH). The ultrasonography results were confirmed by X-ray venography. Two of these patients were without clinical symptoms of hepatic involvement apart from a slight increase in transaminases. This study indicates, firstly, that ultrasonic scanning is a rapid and reliable diagnostic tool in monitoring patients for this serious and often fatal complication, and, secondly, that hepatic venous thrombosis may be a more common complication in PNH than previously assumed.
Adult↗
The concentration of lactoferrin in tears of normals and of diabetics.
The tear lactoferrin content and the tear secretion rate was determined in 105 normal subjects (age range: 15-93 years) and 21 diabetic patients (age 21-78 years). Tear sampling was performed using glass capillaries and the lactoferrin concentration in tears was tested employing an enzyme-linked immunosorbent assay. Tear secretion rate was measured using standardized Halberg filter paper placed in the inferior fornix for 5 min. The lactoferrin level of normal tears showed a significant inverse correlation with age, the mean value of the 8th decade (0.81 mg/ml) constituting only about half the value of the lactoferrin level found in the 3rd decade (1.48 mg/ml). The tear secretion rate also displayed a significant decrease with age, but no correlation could be demonstrated between the tear secretion rate and lactoferrin concentration. No difference was found in lactoferrin level between men and women. We were not able to demonstrate any correlation between lactoferrin content of tears and the duration of diabetes in the 21 diabetic subjects, and there was no difference between the level of lactoferrin in normal tears compared to the concentration in diabetic tears. No difference was found between the tear secretion rate in normals and in diabetics.
Adolescent↗