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 mortality and morbidity in abdominal surgery were investigated in two groups of patients, one with empty (N = 228) and the other with normal (N = 220) iron stores before operation. The estimation of body iron stores by measurements of serum ferritin concentration assumes that the only reason for a low ferritin value is an empty iron store. The results showed that the period of hospital treatment was shorter and the number of complications, especially infections, fewer, in patients with normal as compared to empty iron stores before the operation (p less than 0.001). These differences were especially striking in patients subjected to gastric or large bowel surgery. The results were not explained by differences in sex, age, serum albumin, or clinical anemia. The complications were not predictable from preoperative serum albumin, alkaline phosphatase, or alanine amino transferase levels. Among patients with postoperative complications those with preoperative empty iron stores also had a lower preoperative blood hemoglobin concentration (127 +/- 10 g/liter) than those with normal preoperative iron stores (136 +/- 9 g/liter). Thus it is speculated that the mechanisms behind postoperative complications due to preoperative empty iron stores might be a decrease in tissue oxygenation, resulting in an increased fatigue while working, decreased contractile capacity of the respiratory muscles, and a decrease in immune function. Thus a measurement of serum ferritin concentration and correction of empty iron stores is recommended before abdominal surgery.
 ...
PMID:Empty iron stores as a significant risk factor in abdominal surgery. 339 23

A 90% small bowel resection in 8 dogs resulted in a significant decrease (p less than 0.05) in D-xylose and D-glucose absorption during the early postoperative period. The absorptive capacity of the residual gut with regard to L-alanine, however, remained unchanged. Anemia and hypoalbuminemia also occurred in time, suggesting a malabsorptive state. Control studies were performed in 8 dogs with small bowel transections. The results suggest that a high protein diet might be of benefit during the early postoperative period after massive small bowel resection.
 ...
PMID:Glucose and alanine absorption following massive small bowel resection. 340 15

Clarified slurry oil (CSO), the heavy residual fraction from the fluidized catalytic cracker, was applied to the shaven backs of groups of 10 male and 10 female Sprague-Dawley rats 5 days/week for 13 weeks at doses of 8, 30, 125, or 500 mg/kg/day, and to another group for 2 weeks at doses of 2000 mg/kg/day. The rats were fitted with cardboard Elizabethan collars to minimize the ingestion of the test material, which was applied undiluted and remained uncovered on the skin. A similar group of rats served as controls; they were treated in the same manner except that no CSO was applied to their skin. There was a dose-related mortality and depression of body weight gain in the rats treated with CSO at doses of 30 mg/kg/day or greater; none of the rats dosed at 2000 mg/kg/day survived more than 2 weeks. The primary target organs of CSO toxicity were the liver, thymus, and bone marrow. The effects on the liver included increased weight (250% at 500 mg/kg/day), cholangiolitis, diffuse liver cell degeneration and hypertrophy, necrosis, fibrosis, decreased serum glucose, increased levels of alkaline phosphatase, aspartate aminotransferase, alanine amino transferase, bilirubin, and triglycerides. The thymus was found to be small and upon microscopic examination to be atrophic or hypoplastic. Erythroid hypoplasia was found in the bone marrow of some of the rats dosed at 30 mg/kg/day and increased in severity with increasing dose. The erythroid hypoplasia was accompanied by a dose-related anemia. Even in the rats dosed at 8 mg/kg/day, very slight abnormalities in the bile ducts were observed upon microscopic examination of the liver. Chromatographic separation and analyses demonstrated that CSO contains about 58% 3- to 5-ring polycyclic aromatic hydrocarbons (PAHs) and approximately 8-10% carbazole derivatives. In vitro and in vivo skin penetration studies demonstrated that the carbazole materials penetrate through the skin to a considerable extent (about 44%); less penetration was observed with 2- or 3-ring (8-13%) or 5-ring PAHs (3%).
 ...
PMID:Systemic toxicity from subchronic dermal exposure, chemical characterization, and dermal penetration of catalytically cracked clarified slurry oil. 359 Jan 98

Hb Knossos is a beta-chain variant (beta 27 Ser----Ala) that is unrecognizable by conventional separation methods but detectable by globin electrophoresis on urea-Triton X-acrylamide gels or by IEF. Hb Knossos is characterized by reduced synthesis and by interaction with beta-thalassemia, in which the double heterozygotes display typical features of thalassemia intermedia. The present paper summarizes the salient genetic, clinical, and biochemical characteristics of five such cases hitherto identified in three families along with the same features on 12 heterozygous Hb Knossos carriers. Hb Knossos displays a slightly decreased oxygen affinity; this factor may compensate in part for the severe anemia of the double heterozygotes. Hb Knossos is relatively rare in our population, since a prospective survey on 610 individuals has failed to disclose any heterozygotes. However, the mutation appears to have spread over the Mediterranean countries and may be more common elsewhere.
 ...
PMID:Hemoglobin Knossos: a clinical, laboratory, and epidemiological study. 394 30

Erythropoietin (EPO) is the primary hormone responsible for the growth and maturation of red blood cells in mammals. In contrast to many other growth factors, the specificity of EPO for mature erythroid cells has lead to its development as a safe and efficacious therapeutic, EPREX. The medical benefits of EPREX have been well established in the treatment of anaemic chronic renal failure patients, anaemic HIV patients treated with AZT, cancer chemotherapy patients, and patients wishing to donate their own blood prior to elective surgery (autologous predonation). Due to the chronic nature of EPO therapy, it would be desirable to have an orally administered 'second generation' molecule. An understanding of the structural basis of the interaction of EPO with its receptor will aid in the design of an oral anaemia drug. In this study, a series of mutations have been generated in a truncated form of the receptor comprising the extracellular region, termed EPO binding protein (EBP). One mutant, in which alanine replaces phenylalanine at position 93 (F93A) has a 500-fold reduction in binding compared to wild-type EBP. A neutralizing anti-EBP antibody binds poorly to the F93A mutant, while a non-neutralizing anti-EBP antibody binds wild-type and F93A equally well. Information from this mutational analysis can be applied to a receptor 3-D model and ultimately used in drug development.
 ...
PMID:Erythropoietin receptor: application in drug development. 764 2

We have identified through sequencing of amplified DNA a GCC-->GAC mutation in codon 115 of the beta-globin gene in a mother and daughter of a small Czech family. This base change was confirmed by hybridization with a 32P-labeled specific oligonucleotide probe and by gene mapping because it creates a new Ava II site. The mutation results in an Ala-->Asp replacement at beta 115(G17); this beta chain is severely unstable and could not be identified either as chain or as hemoglobin variant by isoelectrofocusing and various high performance liquid chromatography methods. Stability tests were mildly positive in freshly prepared lysates, but an unstable hemoglobin could not be detected in older lysates with these methods. Its presence results in a dominant type of beta-thalassemia in the two heterozygotes, with moderate anemia, reticulocytosis, nucleated red cells, target cells, and other red cell changes, Heinz body formation, and splenomegaly; the oldest of the two patients was splenectomized. Both subjects had a marked increase in fetal hemoglobin synthesis.
 ...
PMID:Hb Hradec Kralove (Hb HK) or alpha 2 beta 2 115(G17)Ala-->Asp, a severely unstable hemoglobin variant resulting in a dominant beta-thalassemia trait in a Czech family. 769 20

Human erythrocyte protein 4.2 (band 4.2; pallidin) is a major membrane protein that comprises 5% of the total weight of the human erythrocyte membrane. Deficiencies of this protein have been observed in hereditary spherocytosis with anaemia, suggesting a role of protein 4.2 in erythrocyte stability and integrity. The molecular basis of this disorder remains unknown. As a first step in elucidating the pathogenesis of hereditary spherocytosis associated with protein 4.2 deficiency, we cloned and sequenced the erythrocyte protein 4.2 gene from a normal Japanese person. We prepared sets of oligonucleotide primers for polymerase chain reaction (PCR) and determined nucleotide sequences of exons and exon-intron boundaries of the protein 4.2 gene from three unrelated Japanese patients with hereditary spherocytosis due to a complete defect of protein 4.2, using PCR-related techniques. Two patients were homozygous for a missense mutation in codon 142 with the Ala (GCT)-->Thr (ACT) amino acid substitution that has been reported previously (protein 4.2NIPPON), whereas one patient was compound heterozygous for the same missense mutation in codon 142 and a guanine-adenine transition in codon 119 that changes the codon for Trp (TGG) to the termination codon (TGA) (protein 4.2Fukuoka). No additional mutation was identified in other exons of the protein 4.2 genes. Dot-blot hybridization with allele-specific oligonucleotide probes showed that homozygosity for the missense mutation in codon 142 and compound heterozygosity for the codon 142 and the codon 119 mutations were related to protein 4.2 deficiency in the families. Although two alleles of missense mutation of the codon 142 were also detected in 100 alleles of healthy Japanese, results obtained in this study indicate that the two mutations described above are closely related to the pathogenesis of hereditary spherocytosis due to protein 4.2 defect.
 ...
PMID:A novel mutation in the erythrocyte protein 4.2 gene of Japanese patients with hereditary spherocytosis (protein 4.2 Fukuoka). 781 64

A 38-year-old Swedish woman was investigated because of mild anaemia resistant to iron therapy. Mild haemolytic disease was found by routine blood tests. Neither HPLC (HbA1c quantification) nor Hb-electrofocusing revealed any major abnormal fraction, although in vitro testing of haemoglobin instability indicated the presence of unstable haemoglobin. PCR was used to amplify coding regions of the beta globin gene. Direct nucleotide sequencing of this material revealed heterozygosity for a substitution corresponding to the haemoglobin variant alpha 2 beta 2 135(H13)Ala-->Pro. This clearly unstable variant, named Hb Altdorf, has earlier been described only in a family of Italian descent. Examination of beta globin genes from six family members of the proposita by PCR followed by specific cleavage with the restriction enzyme Ban I, revealed the mutation in her two children but not in her parents or siblings. This case demonstrates that haemoglobin variants can not be ruled out as a cause of haematological disease even if the parents lack symptoms and standard tests, such as HPLC and electrophoresis/electrofocusing, do not reveal major abnormalities.
 ...
PMID:Unstable haemoglobin causing haemolytic anaemia: de novo mutation in Sweden identified by PCR. 845 Mar 1

The plasma amino acid pattern has been investigated in severely anemic Belgrade laboratory (b/b) rats. Nonanemic heterozygous (b/+) or normal homozygous (+/+) rats of the same age (six weeks) were used as controls. Decreased plasma proteins, increased total free amino acid, and urea concentrations in plasma associated with increased urea and 3-methylhistidine urinary excretion were found, indicating protein and amino acid metabolic alterations in anemic b/b rats. Plasma alanine, glutamine, tyrosine, and phenylalanine concentrations were increased. The significantly reduced molar ratio between valine+leucine+isoleucine and phenylalanine+tyrosine suggested severe disturbance in the hepatic energy-producing system and derangement of hepatic energy status. Partial or complete reversal of the anemia within 3 days by red blood cell transfusion or within 3 weeks by iron treatment resulted in normalization of tyrosine, alanine, glutamine, and total amino acid concentrations in plasma, as well as of molar ratio between valine+leucine+isoleucine and phenylalanine+tyrosine. This indicated a better oxygen supply to the liver and normalization of the hepatic energy status. These findings suggest that the metabolic disturbances in the b/b rat are the consequence of hypoxia due to the severe anemia.
 ...
PMID:Decreased plasma proteins, increased total plasma-free amino acids, and disturbed amino acid metabolism in the hereditary severe anemia of the Belgrade laboratory (b/b) rat. 851 48

Trichuris suis, the whipworm of swine, causes anemia, weight loss, anorexia, mucohemorrhagic diarrhea, and death in heavy infections. A zinc metalloprotease has been suggested to play a role in the severe enteric pathology associated with infection and the infiltration of opportunistic bacteria into deeper tissues in the swine colon. In this study, a thiol protease from gut extracts of adult T. suis and from excretory/secretory components (E/S) of adult worms was characterized using fluorogenic peptide substrates and protein substrate gels. The protease cleaved the fluorogenic substrate Z-Phe-Arg-AMC, and this cleavage was completely inhibited by the thiol protease inhibitors E-64, leupeptin, Z-Phe-Ala-CH2F, and Z-Phe-Arg-CH2F. Gelatin substrate gels and fluorescence assays using both the gut and the stichosome extracts and E/S revealed enhanced activity when 2 mM dithiothreitol or 5 mM cysteine was included in the incubation buffer, and optimal activity was seen over a pH range of 5.5 to 8.5. Incubation of gut extracts or E/S material with inhibitors of aspartic, serine, or metalloproteases had no effect on the cleavage of Z-Phe-Arg-AMC. Thiol protease activity was found in extracts of gut tissue but not in the extracts of stichocytes of adult worms. N-terminal amino acid sequencing of the protease revealed sequence homologies with cathepsin B-like thiol protease identified from parasitic and free-living nematodes.
 ...
PMID:Trichuris suis: thiol protease activity from adult worms. 902 2


<< Previous 1 2 3 4 5 6 7 8 9 Next >>