Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The etiology of anemia in cancer is not fully understood. A possible cause of the anemia of tumor-bearing animals could be a decreased activity in the enzymes of the heme-pathway. We report the enzyme activity of porphobilinogen-synthetase in the liver of Yoshida sarcoma-bearing rats. PBG-synthetase activity in the whole liver, is higher in tumor-bearing rats than in controls, although the enzyme activity by a gram of wet liver is decreased. Hence PBG-synthetase activity is not a limiting factor in the biosynthesis of heme in tumor-bearing animals.
 ...
PMID:PBG-synthetase activity in the liver of Yoshida sarcoma-bearing rats. 48 94

Normal or increased amounts of series III porphyrins with greater amounts of series I were observed on incubation of PBG in hemolysates of congenital erythropoietic porphyria vs. normal erythrocytes, human or bovine. Correlation with reticulocyte percentage was poor, in the aggregate a general trend toward increased values of both isomers I and III was noted with increasing reticulocytes. When the percent of type III was low the net amount was increased as compared with normal. Hemolysates of non-porphyric, reticulocyte-rich red cells (hemolytic or posthemorrhagic anemia) formed only minute amounts of type I porphyrin but at the same time no more, or even less type III than the porphyric hemolysates, although representing red cells of greater reticulocyte content. No evidence of deficient heme synthesis was observed in porphyric hemolysates incubayed with [14C]-porphobilinogen or 59Fe. Other studies of porphyric hemolysates incubated with and without added mouse spleen synthetase failed to reveal evidence of an absolute UPG-III cosynthetase (Co-S) deficiency. The large increases of type I porphyrin with normal or increased formation of type III, both in the disease and in the hemolysates, are believed due to a primary increase of ALA-S or UPG-S activity rather than a decrease of Co-S. Possible mutations which might be responsible for this increase are considered.
 ...
PMID:The activities of uroporphyrinogen synthetase and cosynthetase in congenital erythropoietic porphyria (CEP). 98 34

We describe a spot test for detecting deficiency of uroporphyrinogen I synthase (EC 4.3.1.8), which is characteristic of intermittent acute porphyria. The specimens used for enzyme assay are 6.5-mm filter paper discs saturated with dried blood (less than 15 mul) that was collected by direct application from a fingerstick or from venipuncture, with or without anticoagulant. The enzyme in such specimens is stable for at least nine days at -20 or c degrees C or for two days at room temperature. The discs are incubated with porphobilinogen (0.11 mmol/liter) in tris(hydroxymethyl)aminomethane HCl buffer, pH 8.2, in the dark at 37 degrees C for 3.5 h. Trichloroacetic acid is added and, after centrifugation, the supernate is examined visually with a long-wavelength ultraviolet lamp. Samples from normal and porphyric subjects are readily differentiated, both by color and intensity of the resulting porphyrin fluorescence. Anemia is a potential source of falsely positive tests, but one may accurately determine the concentration of hemoglobin in the whole blood on the filter paper discs. Moreover, the fluorescence of normal but anemic samples clearly differs qualitatively from that of porphyric specimens. Another source of falsely positive tests, variation in enzyme activity creating an overlap zone of normal and porphyric results, has not been a confounding problem. The method thus seems to offer promise for screening populations for this disorder.
 ...
PMID:A spot test for uroporphyrinogen I synthase, the enzyme that is deficient in intermittent acute porphyria. 100 Jul 96

Uroporphyrinogen I synthetase (URO-S) activity in red cells was measured in 49 patients with acute intermittent porphyria (AIP), in their relatives, in 16 patients with variegate porphyria, and in patients with various forms of anaemia. URO-S activity was clearly lower in patients with AIP (mean 30.5 U, SD 9.7) than in controls (mean 49.5 U, SD 6.4) and in patients with variegate porphyria. There was an overlapping of the values of controls and those of AIP patients, seven patients having fully normal values. Out of 63 relatives eight prepubertal children and two adults with normal urine analysis had URO-S activity below normal. Two newborn infants out of the five studied who had a prophyric parent had lowered URO-S activity in cord blood. URO-S activity was usually elevated in anaemias and correlated to the reticulocyte count. It is concluded that measurement of URO-S activity in red cells is a valuable supplementary method in searching for latent cases of AIP. It is the only method that can disclose the disease before puberty and even neonatally. The major limitation is the occurrence of normal values in some patients with AIP.
 ...
PMID:Red cell uroporphyrinogen I synthetase in acute intermittent porphyria. 100 83

Porphyrin metabolism disorders are grouped into three classes. 1) Hereditary porphyrias including those caused by an inherited deficiency in one of the enzymes responsible for porphyrin synthesis. 2) Secondary porphyrias: well defined clinical situations due to disturbed porphyrin metabolism caused by a variety of toxic substances or drugs or secondary to other pathological conditions. 3) porphyrin metabolism disorders as concomitant featured of certain types of poisoning or particular pathologies. This is followed by a brief description of porphyrin synthesis and the enzymes involved in it, and the distribution of porphyrins and their precursors in certain tissues and biological materials. Hereditary porphyrins are treated individually and not classified since all the classification systems proposed are open to criticism. However the value of grouping acute intermittent porphyria, hereditary coproporphyria, variegated porphyria and the porphyria caused by PBG-synthetase deficiency under "acute porphyrias" is recognised since all involve acute attacks with similar symptoms and prognoses, all are triggered by the same factors and all are treated in the same way. The various forms of hereditary porphyrias are grouped into 3 main categories: a) acute attacks featuring abdominal colics and signs of distress on the cerebral and peripheral nervous systems; b) skin alteration due to photosensitisation; c) haemolytic anaemia. Treatment is divided into preventive, symptomatic and aetiopathogenic. The individual hereditary porphyrias are then examined. The secondary porphyrias examined include lead poisoning, porphyria of the skin caused by hexachlorobenzene, subacute or chronic tyrosinaemia and acute intermittent porphyria caused by carbamazepine. Finally the porphyrin metabolism disorders concomitant with other diseases are examined including those encountered in anaemia, liver disease, dermatological conditions and infections and conditions caused by drugs and toxic substances.
 ...
PMID:[Clinical medicine of disorders of porphyrin metabolism in man]. 331 15

We examined the morphological and functional characteristics of erythroblasts derived from marrow erythroid progenitor cells grown in a methylcellulose microculture, which were taken from a female child with rare atypical sideroblastic anaemia (SA) partially responsive to pyridoxine. Colony formation was within the normal range in three successive cultures (median values: 82.25 CFU-E and 16.4 BFU-E derived colonies/6.6 X 10(4) cells) compared to growth by normal cells (65-315 CFU-E and 9-40 BFU-E). We evaluated in vitro differentiation by biochemical microassay of a cytosol enzyme involved in the haem pathway: uroporphyrinogen I synthase (UROS). The UROS values in the erythroid colonies from SA marrow were at the lowere end of the normal range (median values: 6.7 +/- 0.3 and 14.4 +/- 3.8 pmol uroporphyrinogen/h in CFU-E and BFU-E-derived colonies respectively versus 17.4 +/- 7.3 and 25 +/- 7.2 pmol/h in CFU-E and BFU-E colonies from normal subjects. Ultrastructural examination of the SA erythroblasts from non-cultured bone marrow or derived from cultured BFU-E revealed the characteristic deposition of iron in mitochondria around the nucleus of most cells (ringed sideroblasts). However, the majority of cultured cells had marked dyserythropoietic features, with a large number of bilobulated or trilobulated erythroblasts, multiple cytoplasmic vacuoles, numerous abnormalities of the nucleus, and excessive membrane material beneath the plasma membrane, all features difficult to observe in non-cultured marrows.
 ...
PMID:A paediatric case of sideroblastic anaemia. Ultrastructural studies of erythroblasts cultured from marrow BFU-E in a methylcellulose micromethod. 379 91

We studied the effect of natural and synthetic androgens on children's erythropoietic precursor cells in culture. Cultures of normal marrow were carried out according to a miniaturized methylcellulose method in the presence of erythropoietin. We then evaluated the effects of testosterone, nortestosterone, fluoxymesterone and etiocholanolone (10(-9)-10(-6) M) on erythroid colony-forming units (CFU-E) and burst-forming units (BFU-E). Androgen-induced growth of erythroid progenitors was quantified by directly scoring colonies and by a biochemical determination of the uroporphyrinogen I synthase activity (UROS). We observed a significant increase (p less than or equal to 0.05) in the number of CFU-E and BFU-E and in the UROS activity of derived colonies in the presence of androgens (10(-8) or 10(-7)M). This microculture assay could be useful not only to study the effect of androgens on erythroid progenitor cells in culture, but also to predict the best androgenic treatment of anemia in children and adults.
 ...
PMID:Stimulatory effects of androgens on normal children's bone marrow in culture: effects on BFU-E, CFU-E, and uroporphyrinogen I synthase activity. 394 73

The effects of natural and synthetic androgens on erythroid colony formation in children's bone marrow cultures were studied using a methylcellulose microculture assay. In an attempt to predict the clinical response to androgens in two children with Fanconi anaemia (FA) and two children with Diamond-Blackfan syndrome (DB), we tested the hormonal stimulation of testosterone, nortestosterone and etiocholanolone on CFU-E, BFU-E and uroporphyrinogen I synthase activity (UROS). We observed that colony formation and UROS activity were reduced when compared to values obtained with normal children's bone marrow cultures. The addition of steroids to the cultures significantly enhanced the numbers of CFU-E and BFU-E derived colonies and their UROS activity in marrow from patients with FA and one patient with DB. The strong depletion of marrow progenitor cells in the unresponsive marrow from child 4 with DB could explain the absence of hormonal response. Whereas the responsiveness to steroids varied according to the individual, the in vitro testing of erythroid differentiation in the presence of androgens theoretically may lead to an effective prediction of response to therapy in children with hypoplastic anaemia.
 ...
PMID:In vitro CFU-E and BFU-E responses to androgen in bone marrow from children with primary hypoproliferative anaemia: a possible therapeutic assay. 395 34

Unexpected differences in clinical and biochemical findings in two brothers occupationally exposed to the same source of lead for dissimilar lengths of time are presented. Only the brother with the shorter period of lead exposure was anemic and afflicted by nausea, vomiting, abdominal colic and arthralgia. His urinary PBG output yielded the high orders of magnitude found in acute intermittent porphyria in relapse. Prior to administration of a single dose of EDTA (1 g of the calcium disodium salt given intravenously in 325 mL 0.15 mol/L NaCl), his blood lead levels averaged 3.6 mumol/L. The amount of chelatable lead retrieved from his urine, 31 mumol/day, was more than twice that found in his asymptomatic counterpart who was exposed to lead for 13 months and whose pre-EDTA blood lead levels averaged 4.0 mumol/L. Not only the activity of delta-aminolaevulinic acid dehydratase, but also that of uroporphyrinogen I synthetase, was markedly inhibited by lead in red cells of both brothers. These activities were restored to normal levels in vitro by addition to the assay system of zinc and dithiothreitol. This ruled out a coexisting genetic deficiency of either enzyme. The anemia of the symptomatic brother with the shorter period of lead exposure was alleviated by folic acid, 15 mg/day. The differences in findings between the two brothers point to differential susceptibility to lead and illustrate the extent to which symptomatic lead poisoning may mimic biochemical and clinical features of the acute porphyrias.
 ...
PMID:Occupational lead exposure: studies in two brothers showing differential susceptibility to lead. 401 20

The effects of acute ethanol ingestion on the activities of the enzymes of haem biosynthesis in peripheral blood cells have been monitored in eight healthy subjects. The mitochondrial enzymes delta-aminolaevulinic acid (ALA) synthase, coproporphyrinogen oxidase and ferrochelatase were measured in leucocytes and the cytosolic enzymes ALA dehydratase, porphobilinogen (PBG) deaminase and uroporphyrinogen decarboxylase in erythrocytes. Ingestion of 1 . 316 mol ethanol resulted in increased activity of the rate-controlling enzymes ALA synthase and PBG deaminase and decreased activity of the other four enzymes. There was also increased urinary excretion of coproporphyrin. These observations may be relevant to the biochemical mechanisms involved in the ethanol-related conditions, sideroblastic anaemia, cutaneous hepatic porphyria and hepatic siderosis.
 ...
PMID:Acute ethanol ingestion and haem biosynthesis in healthy subjects. 678 Mar 56


1 2 Next >>