Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When human marrow cells were cultured in a medium containing alpha-medium, methylcellulose, fetal calf serum, bovine serum albumin, erythropoietin, and leucocyte-conditioned medium, mixed colonies composed of erythrocytic cells and granulocytes were formed. The clonal nature of the mixed colonies was confirmed by the linear relationship between the numbers of cells plated and the number of colonies, and the absence or presence of Y-chromatin in the mixed colonies in a co-culture experiment with male and female cells. Using the methylcellulose cell culture techniques, the pluripotent hemopoietic precursors (CFUMIX) in marrow cells from 15 patients with aplastic anemia were assayed. In the control subjects of patients with iron-deficiency anemia, lymphoadenitis, reactive leucocytosis or Hodgkin's disease, 8 X 10(5) marrow cells in 4 dishes produced 12.7 +/- 6.9 (mean +/- SD) mixed colonies. On the other hand, 8 X 10(5) marrow cells from patients with aplastic anemia formed only 2.1 +/- 5.5 (mean +/- SD) mixed colonies. Furthermore, the marrow cells from 5 patients who were repeatedly receiving transfusions contained no CFUMIX which give rise to mixed colonies. The present results provided the first direct evidence that pancytopenia in most patients with aplastic anemia results from a reduced influx into the compartment of maturing hemopoietic cells from the compartment of pluripotent hemopoietic precursors.
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PMID:Pluripotent hemopoietic precursors in vitro (CFUMIX) in aplastic anemia. 722 71

Ferritin, an iron-storing protein, was isolated from disease-involved and -uninvolved regions of spleen biopsies obtained from patients with Hodgkin's disease (HD). Ferritin from all human spleen biopsies showed a major band of polypeptide of M(r) around 20 kDa in 1D-SDS-PAGE analysis. The corresponding bands for horse spleen ferritin and apoferritin (Sigma) were at a slightly lower M(r) level. In isoelectrofocusing (IEF) studies, the pI values of human spleen ferritin from the uninvolved and involved regions were 4.55 and 4.14, respectively. These were more acidic than that of horse spleen ferritin (4.79). Human spleen ferritin from the involved region also differed from that of the uninvolved region in the pattern of CNBr-generated peptide maps in 1D-SDS-PAGE. These results suggest that the presence of Hodgkin's disease in human spleen is associated with some physiochemical changes in the tissue ferritin.
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PMID:Characterization of ferritin from spleens of patients with Hodgkin's disease (HD). 835 Sep 46

Intermittent painful crises due to vasoocclusion are the major clinical manifestation of sickle cell disease (SCD), but subclinical episodes may also occur. There is sparse evidence for the involvement of neutrophils in the pathophysiology of SCD, but production of cytokines by the damaged endothelium might influence neutrophil function and modulate responses to subsequent cytokine exposure. In addition, the activation of neutrophils in the microcirculation could itself exacerbate vasoocclusion. To test whether neutrophil inflammatory responses were altered in SCD, neutrophil phospholipase A2 and NADPH oxidase activity in response to in vitro priming by granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha) were measured both during and between painful crises. Resting levels of neutrophil phospholipase A2 activity in steady-state SCD (4.0% +/- 0. 5% of total cell radioactivity) were raised relative to control values (2.0% +/- 0.2%, n = 10, P = .008). There was no defect of agonist-stimulated phospholipase A2 or NADPH oxidase activity in steady-state SCD; however, the ability of phospholipase A2 to respond to priming with GM-CSF was attenuated to 63% +/- 17% of control values (n = 10, P = .04). Similarly, neutrophil NADPH oxidase activity after priming with GM-CSF and TNF-alpha was, respectively, 65% +/- 11% (n = 7, P = .03) and 57% +/- 7% of control (n = 10, P = .007) in steady-state disease, and was further reduced during painful vasoocclusive crises to 34% +/- 9% and 25% +/- 3% of control for GM-CSF and TNF-alpha, respectively. These data were not explained by poor splenic function or any racial factor, as normal cytokine responses were seen in splenectomized patients in remission from Hodgkin's disease and in healthy Afro-Caribbean subjects. Abnormal neutrophil cytokine priming responses were not observed in either patients with rheumatoid arthritis or iron-deficiency anemia. Our findings are indicative of an ongoing inflammatory state in SCD between painful crises involving neutrophil activation and an abnormality of cytokine-regulated neutrophil function, which may compromise the host defenses against certain microorganisms.
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PMID:Raised neutrophil phospholipase A2 activity and defective priming of NADPH oxidase and phospholipase A2 in sickle cell disease. 955 1

The two proteins ferredoxin and flavodoxin can replace each other in the photosynthetic electron transfer chain of cyanobacteria and algae. However, structure, size, and composition of ferredoxin and flavodoxin are completely different. Ferredoxin is a small iron-sulfur protein (approximately 100 amino acids), whereas flavodoxin is a flavin-containing protein (approximately 170 amino acids). The crystal structure of both proteins from the cyanobacteria Anabeana PCC 7120 is known. We used these two protein structures to investigate the structural basis of their functional equivalence. We apply the Hodgkin index to quantify the similarity of their electrostatic potentials. The technique has been applied successfully in indirect drug design for the alignment of small molecule and bioisosterism elucidation. It requires no predefined atom-atom correspondences. As is known from experiments, electrostatic interactions are most important for the association of ferredoxin and flavodoxin with their reaction partners photosystem I and ferredoxin-NADP reductase. Therefore, use of electrostatic potentials for the structural alignment is well justified. Our extensive search of the alignment space reveals two alignments with a high degree of similarity in the electrostatic potential. In both alignments, ferredoxin overlaps completely with flavodoxin. The active sites of ferredoxin and flavodoxin rather than their centers of mass coincide in both alignments. This is in agreement with electron microscopy investigations on photosystem I cross-linked to ferredoxin or flavodoxin. We identify residues that may have the same function in both proteins and relate our results to previous experimental data.
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PMID:Structural alignment of ferredoxin and flavodoxin based on electrostatic potentials: implications for their interactions with photosystem I and ferredoxin-NADP reductase. 1071 90

This study assessed the changes in the isoprenoid pathway and its metabolites digoxin, dolichol and ubiquinone in neoplasms (CNS astrocytomas - glioblastoma multiforme and high grade non - Hodgkin's lymphoma). The following parameters were assessed-isoprenoid pathway metabolites, tyrosine and tryptophan catabolites, glycoconjugate metabolism, RBC membrane composition and free radical metabolism. There was an elevation in plasma HMG CoA reductase activity, serum digoxin and dolichol and a reduction in RBC membrane Na+-K+ ATPase activity, serum ubiquinone and magnesium levels. Serum tryptophan, serotonin, nicotine and quinolinic acid were elevated while tyrosine, dopamine, noradrenaline and morphine were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions (except dermatan sulphate in the case of CNS astrocytomas), the activity of GAG degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins and serum glycolipids were elevated. HDL cholesterol showed a significant decrease and free fatty acids & triglycerides were increased. The RBC membrane glycosaminoglycans, hexose and fucose residues of glycoproteins and phospholipids were reduced. The activity of all free radical scavenging enzymes, concentration of glutathione, iron binding capacity and ceruloplasmin decreased significantly while the concentration of malondialdehyde (MDA), hydroperoxides, conjugated dienes and NO increased. The concentration of alpha tocopherol was unaltered. Membrane Na+-K+ ATPase inhibition due to elevated digoxin, altered membrane structure and digoxin related tyrosine / tryptophan transport defect leading to increased levels of depolarising tryptophan catabolites and decreased levels of hyperpolarising tyrosine catabolites can lead to alteration in intracellular calcium/magnesium ratios and oncogene activation. Intracellular magnesium deficiency can produce defective microtubule related spindle fibre dysfunction and chromosomal non-dysjunction contributing to neoplastic cellular polyploidy and aneuploidy. Digoxin induced tryptophan/tyrosine transport defect can alter neurotransmitter patterns with increased serotonin, quinolinic acid, nicotine & glutamatergic transmission and reduced dopamine, morphine and noradrenaline levels leading to oncogenesis. Glycoconjugate metabolism is altered by elevated dolichol levels and magnesium depletion consequent to Na+-K+ ATPase inhibition. There is a qualitative alteration in proteoglycans and glycoproteins, defective membrane formation and structure and reduced lysosomal stability leading to disordered contact inhibition and tumour antigen presentation contributing to oncogenesis. Digoxin induced alteration in intracellular calcium/magnesium ratios and low ubiquinone levels can lead to a mitochondrial dysfunction resulting in increased free radical generation and reduced scavenging & caspase-3 activation producing a P21 defect contributing to oncogenesis.
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PMID:Hypothalamic digoxin mediated model for oncogenesis. 1187 54

The gene causing hereditary hemochromatosis (HH), HFE is an HLA class I-like gene with no known immunological function but indirectly related to the immune functions because of its role in iron transport. It is located 6.5 Mb telomeric to HLA-A. The most common mutation of HFE, C282Y, has a Celtic origin and most patients with HH are homozygous for it in Northern European populations. While there is an enormously increased risk for hepatocellular cancer in hemochromatosis that is attributed to the toxic effects of iron, the risk for extra-hepatic cancers is also increased slightly. Recent studies have found genetic associations between several cancers and C282Y but only in the presence of a particular allele of the transferrin receptor gene. This suggests that the increased cancer risk is more likely due to the effects of iron. In childhood acute lymphoblastic leukemia (ALL), however, there is a strong association of C282Y with a gender effect in two different Celtic populations. This association does not require homozygosity for C282Y or an interaction with the transferrin receptor gene, and is male-specific. The other HFE mutation H63D does not confer increased risk to childhood ALL. Acute myeloblastic leukemia and Hodgkin's disease in adults do not have an association with HFE. Its male-specificity, occurrence in childhood and the lack of a gene-dosage effect suggest that the C282Y association in childhood ALL may reflect the involvement of another HLA-linked gene in leukemia susceptibility.
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PMID:Hemochromatosis gene in leukemia and lymphoma. 1200 48

Soluble transferrin receptor levels in serum (s-sTfR) may be useful in differentiating between iron deficiency anemia and anemia of chronic disease. However, there is both theoretical and clinical evidence for elevated s-sTfR levels in patients with various hematological malignancies. In the present study, routine bone marrow aspirations were performed in 82 patients with malignant lymphomas (63 with non-Hodgkin's lymphoma and 19 with Hodgkin's disease). Smears were stained for evaluation of iron stores and graded. Patients were also given a disease score based on bone marrow morphology, erythrocyte sedimentation rate and LDH. s-sTfR levels correlated better with disease score [partial Spearman rank correlation coefficient (r(s)) controlled for iron stores was 0.51 (95% confidence interval 0.39-0.65); p < 0.001] than with iron stores [partial r(s) controlled for disease score was -0.25 (95% confidence interval -0.44 to -0.03); p = 0.027]. This study showed elevated s-sTfR levels in patients with malignant lymphomas without any signs of iron deficiency anemia. The diagnosis of iron deficiency anemia should not be established upon the basis of s-sTfR alone in this group of patients.
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PMID:Serum levels of soluble transferrin receptor correlate with severity of disease but not with iron stores in patients with malignant lymphomas. 1221 95

X-radiation remains the treatment of choice in most cases of leukemia and lymphoma, but new agents are playing an increasing role in therapy. Radioactive phosphorus does not produce radiation sickness and results with it are comparable to those of x-ray therapy in chronic leukemia. Urethane and nitrogen mustard may produce remissions in patients with chronic leukemia who have become resistant to radiation. Triethylene melamine may be administered orally with nitrogen mustard-like effects and is undergoing further trial. Aminopterin, ACTH and cortisone often cause short remissions in acute leukemia. Urethane is the best treatment available for multiple myeloma. Polycythemia vera is well controlled by radioactive phosphorus combined with venesection. Nitrogen mustard is often effective and triethylene melamine shows promise in Hodgkin's disease. Antianemic substances such as iron and liver extract are of no value in the treatment of anemia caused by leukemia, lymphoma and myeloma.
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PMID:New therapy for leukemia, polycythemia, and lymphoma. 1301 1

We compared bone marrow findings in 2 groups of patients with AIDS during 2 different periods: group 1, n = 20; male/female ratio, 19/1; and group 2, n = 120; male/female ratio, 6/1. Bone marrow iron stores were decreased significantly in group 2 (P < .01), and the incidence of AIDS-related lymphomas was higher, with frequent bone marrow involvement. Two group 1 patients had Kaposi sarcoma, and a 21-month-old girl with transfusion-transmitted AIDS had Burkitt-like lymphoma. In group 2, 44 patients had a history of malignant neoplasms, including Kaposi sarcoma (10 cases), hematologic neoplasms (33 cases), and metastatic leiomyosarcoma (1 case). Of the 120 patients, 15 (12.5%) had bone marrow involvement by malignant neoplasms. The majority of the non-Hodgkin lymphomas were high-grade lymphomas. Patients with AIDS-related malignant neoplasms had higher CD4+ cell counts and viral loads than patients without malignant neoplasms (P < .01, P < .05, respectively). The finding of decreased iron stores in patients with AIDS might aid clinical management of their anemia. The increased incidence of malignant neoplasms, especially lymphomas, in recent years might be related to prolonged survival but with incomplete reconstitution of immune function after antiretroviral therapy.
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PMID:Changing pattern of AIDS: a bone marrow study. 1502 44

We present a patient with Hodgkin's disease in whom computed tomography suggested focal lesions in the liver. As no lesions were detected by diagnostic ultrasound, magnetic resonance imaging (MRI) with iron oxide as contrast medium was performed for verification. MRI confirmed at least 3 small lesions. The ultrasound study performed immediately after this MRI scan easily detected these lesions. A biopsy was taken and histology showed infiltrates of Hodgkin's disease. The change in echogenicity of the liver and/or the lymphomatous tissue may be an effect of iron oxide. This observation has not been reported before.
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PMID:Is iron oxide a tissue-specific contrast medium in diagnostic ultrasound? A case report. 1559 40


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