Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently developed techniques for the investigation of iron kinetics were used to study the disturbance of iron metabolism in 19 untreated patients with Hodgkin's diseases (HD). The erythroid abnormality in newly diagnosed HD appears to be confined to those patients with systemic symptoms of weight loss, night sweats and fever, and consists of depression of marrow erythroid activity. These patients had a significnatly lower haemoglobin and serum iron concentration and a higher serum ferritin concentration, both when compared to normal subjects and to those patients with HD who lacked systemic symptoms. Ineffective erythropoiesis and red-cell destruction were not significantly increased. The present findings, confirm that HD patients with systemic symptoms have a depression of erythropoiesis, and that in these patients the marrow fails to respond to the stimulus of mild anaemia.
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PMID:Erythropoiesis and iron metabolism in Hodgkin's disease. 50 65

1. The effect of iron chelators on iron uptake, ferritin and total protein synthesis was studied in cultured Chang cells. Desferrioxamine depressed ferritin synthesis and completely inhibited iron uptake by ferritin protein. Rhodotorulic acid reduced iron uptake by the cells but had little effect on ferritin synthesis. Diethylenetriamine pentaacetic acid produced complete inhibition of iron uptake and all protein synthesis. 2,3-Dihydroxybenzoic acid (2,3-DHB) had no effect in this system. 2. When 2,3-DHB was incubated with a liver homogenate, its subsequent addition to a Chang cell culture resulted in depression of ferritin synthesis, iron uptake into the protein and some depression of total protein synthesis. Pretreatment of rhodotorulic acid did not affect its properties. 3. Non-ferritin iron in the Chang cell cytosol was dialysable, available for binding to transferrin and formed chelates which appeared, on gel chromatography, to be of low molecular weight. Gel chromatography of cytosol after incubation of the cells with chelating agents showed non-ferritin iron to be in a similar form. 4. Loss of non-ferritin iron from the cells occurred only when the transferrin in the medium was unsaturated. In the presence of chelating agents non-ferritin iron was lost from the cells even when transferrin was 100% saturated. 5. The results confirm the presence of an intracellular labile iron pool which is available for chelation, and demonstration that different iron chelators have different metabolic effects.
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PMID:The effect of chelating agents on cellular iron metabolism. 125 27

Norplant consists of 6 soft plastic capsules placed in the subcutaneous tissue on the inside of the upper arm which release levonorgestrel continuously over 5 years to prevent pregnancy. Health workers use an aseptic technique to insert the capsules within 0.5 cm of the incision. Scar tissue increases removal time to twice that of insertion time. The 1st year pregnancy rate is 0.2%. Body weight affects the cumulative 5-year pregnancy rate: 0.2% for 50 kg women, 3.4-5% for 50-69 kg women, and 8.5 for 70 kg women. It rises remarkably in the 3rd year. Women find the advantages to be, in order of importance, ease of use, effectiveness, long duration, reversibility, and arm placement. The most common misconception about Norplant is it causes cancer or sterility. Both before insertion and during the early months after insertion, family planning providers must thoroughly explain Norplant and stress how it is different from other contraceptive methods. 1 study reveals that the 1-year continuation rate for women who undergo careful preinsertion counseling is greater than it is for women who do not receive effective counseling (88% vs. 60%). The leading side effect is abnormal bleeding patterns. Even though bleeding patterns change, hemoglobin or ferritin levels do not decrease. In women who experience no bleeding, providers must conduct a urinary human chorionic gonadotropin test at 4-6 weeks. If the test reveal no pregnancy, they need to explain to the women that this is normal. Abnormal bleeding patterns improve with increased duration of Norplant use. Women who need to be carefully monitored or should not use Norplant are those with impaired glucose tolerance, hyperlipidemia, impaired liver function, premenstrual symptoms, and history of depression. The ideal candidate is a woman who has used oral contraceptives (OCs) with no side effects yet forgets to take them daily, has contraindications for estrogen, or has estrogenic side effects from OCs.
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PMID:Who is a candidate for Norplant? 161 60

Iron increases the synthesis of the iron-storage protein, ferritin, largely by promoting translation of preexisting mRNAs for both the H and L ferritin isoforms (H, heavy, heart, acidic; L, light, liver, basic). We have recently cloned and sequenced a full-length cDNA to murine ferritin H and identified ferritin H as a gene induced by tumor necrosis factor alpha (TNF-alpha, cachectin). Using primary human myoblasts, we have now examined the relationship between TNF-alpha and iron in regulating ferritin. Four lines of evidence suggest that TNF-alpha regulates ferritin independently of iron. First, evaluation of mRNA showed that TNF-alpha increased ferritin H chain specifically, provoking no change in steady-state levels of ferritin L mRNA; iron, in contrast, increased the mRNA of both isoforms. Second, the increase in ferritin H protein synthesis observed during TNF-alpha treatment was dependent on an increase in ferritin H mRNA: actinomycin D blocked the TNF-alpha-induced changes in ferritin H but did not inhibit the translational induction of ferritin seen with iron treatment. Third, equal ferritin mRNA induction was observed in iron-loaded cells and in cells depleted of iron by a permeant chelator, 2,2'-dipyridyl. Fourth, ferritin H induction by TNF-alpha and iron was additive over the entire range of iron concentrations, even at TNF-alpha doses known to maximally stimulate ferritin H mRNA levels. Nonetheless, the role of iron in translational regulation of ferritin was retained in TNF-alpha-treated cells; effective biosynthesis of TNF-alpha-induced, H-subunit-predominant ferritin protein required iron and could be enhanced by treatment of the cells with additional iron or blocked by 2,2'-dipyridyl. Finally, we observed that the TNF-alpha-mediated increase in ferritin synthesis peaked at 8 hr and was followed by a decrease in both H and L isoferritin synthesis; the addition of iron, however, reversed the late-occurring depression in ferritin synthesis. This suggests that TNF-alpha-induced synthesis of H-rich ferritin may reduce the regulatory pool of intracellular iron, secondarily inhibiting iron-mediated translation of ferritin mRNA. We conclude that TNF-alpha acts independently of iron in its induction of ferritin H mRNA but requires the presence of iron for this effect to be fully expressed at the protein level.
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PMID:Iron-independent induction of ferritin H chain by tumor necrosis factor. 205 77

The membrane protein bacteriorhodopsin was imaged in buffer solution at room temperature with the atomic force microscope. Three different substrates were used: mica, silanized glass and lipid bilayers. Single bacteriorhodopsin molecules could be imaged in purple membranes adsorbed to mica. A depression was observed between the bacteriorhodopsin molecules. The two dimensional Fourier transform showed the hexagonal lattice with a lattice constant of 6.21 +/- 0.20 nm which is in agreement with results of electron diffraction experiments. Spots at a resolution of approximately 1.1 nm could be resolved. A protein, cationic ferritin, could be imaged bound to the purple membranes on glass which was silanized with aminopropyltriethoxysilane. This opens the possibility of studying receptor/ligand binding under native conditions. In addition, purple membranes bound to a lipid bilayer were imaged. These images may help in interpreting results of functional studies done with purple membranes adsorbed to black lipid membranes.
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PMID:Imaging the membrane protein bacteriorhodopsin with the atomic force microscope. 227 63

A 74-year-old female having primary hemochromatosis and hyperthyroidism is described. The initial ECG showed sinus rhythm, and depression of ST segment and inversion of T waves in I, II, III, aVF, and V4-6. By deferoxamine and propylthiouracil, the serum level of ferritin was decreased from 4,500 ng/ml to 440 ng/ml in a period of 6 months. The thyroid function was also returned to normal. After cessation of both drugs, the serum ferritin level increased gradually reaching a level of 3,100 ng/ml in the next 15 months but the thyroid function remained normal. During and after the deferoxamine administration, the depth of inverted T waves became more shallow and gradually deeper again, respectively. There seemed to be a correlation between the depth of inverted T waves and the serum level of ferritin. It was, however, unlikely that toxic iron may have induced the hyperfunction of the thyroid gland.
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PMID:Correlation between the depth of inverted T waves and the serum level of ferritin in a deferoxamine-treated patient with primary hemochromatosis and hyperthyroidism. 273 48

Rat liver ferritin is an effective donor of iron to rat hepatocytes. Uptake of iron from ferritin by the cells is partially inhibited by including apotransferrin in the culture medium, but not by inclusion of diferric transferrin. This inhibition is dependent on the concentration of apotransferrin, with a 30% depression in iron incorporation in the cells detected at apotransferrin concentrations above 40 micrograms/ml. However, apotransferrin does not interfere with uptake of 125I-labeled ferritin, suggesting that apotransferrin decreases retention of iron taken up from ferritin by hepatocytes by sequestering a portion of released iron before it has entered the metabolic pathway of the cells. The iron chelators desferrioxamine (100 microM), citrate (10 mM) and diethylenetriaminepentaacetate (100 microM) reduce iron uptake by the cells by 35, 25 and 8%, respectively. In contrast, 1 mM ascorbate increases iron accumulation by 20%. At a subtoxic concentration of 100 microM, chloroquine depresses ferritin and iron uptake by hepatocytes by more than 50% after 3 h incubation. Chloroquine presumably acts by retarding lysosomal degradation of ferritin and recycling of ferritin receptors.
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PMID:Uptake of ferritin and iron bound to ferritin by rat hepatocytes: modulation by apotransferrin, iron chelators and chloroquine. 291 2

Mononuclear cells in the peripheral blood of 69 previously untreated patients with Hodgkin's disease were investigated and their changes were followed up in the course of the disease. Before the initiation of the treatment, the total number of lymphocytes, cells with ring-shaped nucleolus, E-rosette forming cells and lymphocytes with dot-like ANAE positivity were decreased and ferritin-bearing lymphocytes significantly highly increased (p less than 0.01) when compared with healthy persons. In cells of the monocyte-macrophage lineage, only the total number of cells in initial state of transformation to macrophages (active nucleolus) was significantly highly increased (p less than 0.05). In comparison with early stages, only the changes of quiet, resting cells were significantly more pronounced in advanced disease (p less than 0.01 and p less than 0.05). An excessive depression of ring-shaped nucleolus-bearing cells was associated with B symptoms. Using a discriminant analysis method, the independent influence of these cells upon the immunocompetence of the patients has been proved. After the completion of primary treatment the changes of cells were more profoundly expressed. No complete restauration of immunocompetence has been found within 1-2 years in patients responding satisfactorily to therapy. Verified by the discriminant analysis, persistent imbalance of T-lymphocyte subpopulations plays the most important role in the immune defect of patients in the second year after the therapy and later.
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PMID:Some immunological parameters in Hodgkin's disease. 335 37

The hematologic status of 265 patients with rheumatoid arthritis was assessed. In the group as a whole, a mild depression in the hemoglobin concentration and mean cell volume (MCV) was associated with an increase in the red blood cell distribution width (RDW), erythrocyte sedimentation rate (ESR), and platelet count. Bone marrow trephine biopsies and further measurements of iron status and disease activity were done in [a further] 38 more anemic patients, and the findings in those with absent marrow iron (iron deficiency) were compared with those having stainable stores (anemia of chronic disorders). The RDW was raised in both, and there was no significant difference between the two groups. The concentrations of nonheme iron in the marrow and of serum ferritin were significantly lower in the iron-deficient group, but the geometric mean serum ferritin of 34 micrograms/L was still a good deal higher than that associated with uncomplicated iron deficiency. This was presumably because of the fact that the serum ferritin, which was significantly correlated with the ESR (r 0.55; P less than 0.0004) and C-reactive protein (CRP) r 0.41; P less than 0.01), was also functioning as an acute phase protein. While there was a weak correlation (r 0.37; P less than 0.04) between the marrow nonheme iron and the serum ferritin concentrations, it disappeared when nonactive patients with normal CRP concentrations were excluded. The absence of a correlation is unlike the findings that have previously been noted in other chronic inflammatory conditions and in neoplasia. This raises the possibility that serum ferritin concentrations in rheumatoid arthritis may reflect, in part at least, another store of iron located in affected joints.
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PMID:Hematologic and iron-related measurements in rheumatoid arthritis. 381 50

Chrysotile asbestos fibers impair the activities of rat liver microsomal aryl hydrocarbon hydroxylase (AHH), aminopyrine (AP) N-demethylase and dimethylnitrosamine (DMN) demethylase in vitro. This inhibition is concentration-dependent. Preincubation of 3-methylcholanthrene (3-MC)-pretreated rat liver microsomes with chrysotile depresses the overall metabolism of [G-3H]benzo[a]pyrene (BaP). Various forms of asbestos employed inhibit AHH activity to the same extent. However, other types of asbestos are not as effective as chrysotile in diminishing AP demethylase activity. Chrysotile and crocidolite fibers are not found to significantly change the apparent Km of AHH activity, from 3-MC-pretreated rat liver microsomes, for BaP. Increasing the microsomal protein concentration partially abolishes the inhibition of AHH activity caused by chrysotile fibers. Inhibition of AP demethylase and AHH activities is attenuated by bovine serum albumin (BSA) or ferritin. Depression of AHH activity by crocidolite is significantly reversed by ferritin. Since polymers such as ferritin override enzyme inhibition by chrysotile as well as crocidolite, surface chemical groups of the fibers may be involved in enzyme modification.
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PMID:Effect of asbestos fibers on aryl hydrocarbon hydroxylase and aminopyrine N-demethylase activities of rat liver microsomes. 394 7


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