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

Myelodysplastic syndromes (MDS) are clonal haematological disorders and MDS neutrophils have various abnormal functions which cause an increased risk of infective mortality. We examined luminol-dependent chemiluminescence and cytoplasmic Ca2+ increase in order to characterize the mechanisms of a signalling defect in MDS neutrophil respiratory burst. In MDS patients, chemiluminescence stimulated with N-formyl-L-methionyl-L-leucil-L-phenylalanine (FMLP) and calcium ionophore A23187 was defective (17.2 +/- 13.7 v 44.3 +/- 16.6, P = 0.001; 42.2 +/- 21.3 v 82.0 +/- 23.6, P < 0.05, respectively), but phorbol 12-myristate 13-acetate (PMA) chemiluminescence was normal (73.4 +/- 26.9 v 79.5 +/- 23.8, P = 0.52). There were no statistical significances in cytoplasmic Ca2+ increase stimulated with FMLP and recombinant human interleukin-8 (rhIL-8) compared with controls (251.1 +/- 104.3 v 272.7 +/- 41.2, P = 0.295; 238.6 +/- 65.0 v 253.9 +/- 38.3, P = 0.567, respectively). Flow cytometric analysis of MDS neutrophils disclosed that most MDS patients showed normal neutrophil cytoplasmic Ca2+ response to FMLP and rhIL-8. However, two patients with refractory anaemia with excess of blasts displayed a significant decrease of both chemiluminescence and cytoplasmic Ca2+ response to FMLP, and they also displayed low expression of FMLP receptor. These data suggest that most MDS patients have low FMLP chemiluminescence which is not due to a defect in the FMLP receptor. It is proposed that defective FMLP chemiluminescence in MDS results from a putative defect in protein kinase C- and Ca(2+)-independent cell-signalling mechanisms. Only a small group of patients have numerical or structural defects in the FMLP receptor, causing significant decrease of neutrophil respiratory burst.
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PMID:Signalling defect in FMLP-induced neutrophil respiratory burst in myelodysplastic syndromes. 894 88

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.
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PMID:Trichuris suis: thiol protease activity from adult worms. 902 2

We investigated the DNA of 29 unrelated pyruvate kinase (PK) deficiency (PKD) patients from Central Europe with hereditary nonspherocytic hemolytic anemia for mutations in the PK-L/R gene. Among 58 potentially affected alleles, 53 mutations were identified, of which 17 were different from each other. Of these 17 mutations, 13 were single-nucleotide (nt) substitutions resulting in amino acid exchanges, G787A (Gly263-Arg), G994A (Gly332-Ser), G1006T (Ala336-Ser), G1010A (Arg337-Gln), A1081G (Asn361-Asp), G1127T (Ser376-Ile), G1174A (Ala392-Thr), G1281T (Glu427-Asp), C1454T (Ser485-Phe), C1456T (Arg486-Trp), G1493A (Arg498-His), G1529A (Arg510-Gin), and C1594T (Arg532-Trp); 1 in-frame triplet deletion, 1060delAAG (delLys354); 1 in-frame triplet insertion, 1203insAGC (insSer after Cys401); 1 splicesite mutation, 101-1G-A; and 1 frameshift deletion, 628delGT. Six mutations, 628delGT, G787A, G1010A, G1127T, G1281T, and C1454T, are described for the first time. To test the hypothesis of a single origin of the most common PK mutation in the European population, G1529A, we investigated all patients at four polymorphic sites in the PK-L/R gene: C/A at nt 1705, C/T at nt 1992, the (ATT)n microsatellite in intron J, and a polymorphism (T)10/(T)19 in intron I. Nine patients homozygous for mutation G1529A were consistent in all four markers. In the group of patients homozygous for mutation G1529A, the hematologic parameters and clinical manifestations have been studied in detail. Although having an identical mutation in the PK-L/R gene, the patients are affected differently. Their appearance ranges from a very mild compensated hemolysis to a severe anemia. Possible molecular explanations are discussed.
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PMID:Molecular analysis of 29 pyruvate kinase-deficient patients from central Europe with hereditary hemolytic anemia. 905 65

We examined the inhibitional and nutritional effects of total parenteral nutrition (TPN) containing D-amino acids (D-phenylalanine, D-Phe; D-valine, D-Val; D-leucine, D-Leu; D-methionine, D-Met) on tumor growth in AH109A hepatoma-bearing rats. Five experimental groups were examined: a control amino acid solution group (control group), D-Phe group, D-Val group, D-Leu group and D-Met group. The analysis of tumor volume and weight revealed significant tumor growth inhibition in the D-Val group as compared with the control group. In the D-Val group, decreases of DNA and protein contents in the tumor tissues were also observed. The D-Leu and D-Met groups showed a tendency toward tumor growth inhibition. The protein content in the liver tissues of these two groups was significantly higher as compared with the control group. The DNA content in the liver tissue was also significantly higher in the D-Met group. The body weight including the tumor (on the final day of TPN) was significantly lower in the D-Val group as compared with the control group, but there was no significant difference in the groups for body weights not including tumors (carcass body weight). The hematocrit and hemoglobin values, indicators of anemia, were significantly higher in the D-Val group as compared with the control group. From these results, regarding tumor growth inhibition, the D-Val solution had the strongest inhibitory effect with no negative influence on the host, and improvement of nutritional status was also suggested in the rats that received the D-Leu or D-Met solutions.
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PMID:Tumor growth inhibition and nutritional effect of D-amino acid solution in AH109A hepatoma-bearing rats. 959 Dec 36

In a pilot study, DOTA-d-Phe(1)-Tyr(3)-octreotide (DOTATOC), which can be labelled with the beta-emitting radioisotope yttrium-90, has recently been used for the treatment of patients with advanced somatostatin receptor-positive tumours who had no other treatment option. The aim of the present study was to elucidate the therapeutic potential of (90)Y-DOTATOC in a larger number of patients employing a standardized treatment protocol. Careful attention was paid to any side-effects (renal and/or haematological toxicity). Of 44 patients with advanced somatostatin receptor-positive tumours of different histology, 29 could be included in the study. The 15 patients who were excluded from the study protocol were assigned to our institution for purely compassionate reasons. The 29 patients who were included received four or more single doses of (90)Y-DOTATOC with ascending activity at intervals of approximately 6 weeks (cumulative dose 6120+/-1347 MBq/m(2)) with the aim of performing an intra-patient dose escalation study. In total, 127 single treatments were given. In eight of these 127 single treatments, total doses of > or = 3700 MBq were administered. In an effort to prevent renal toxicity, two patients received Hartmann-Hepa 8% solution during all therapy cycles, while 13 patients did so during some but not all therapy cycles; in 14 patients no solution was administered during the therapy cycles. The treatment was monitored by computed tomography and indium-111 DOTATOC scintigraphy. Blood parameters were controlled weekly, while tumour markers and liver enzymes were controlled 6-weekly. Of the 29 patients, 24 patients showed no severe renal or haematological toxicity (toxicity < or = grade 2 according to the National Cancer Institute grading criteria). These 24 patients received a cumulative dose of < or = 7400 MBq/m(2). Five patients developed renal and/or haematological toxicity. All of these five patients received a cumulative dose of >7400 MBq/m(2) and had received no Hartmann-Hepa 8% solution during the therapy cycles. Four of the five patients developed renal toxicity; two of these patients showed stable renal insufficiency and two require haemodialysis. Two of the five patients exhibited anaemia (both grade 3) and thrombopenia (grade 2 and 4, respectively). To date, 20 of the 29 patients have shown a disease stabilization, two a partial remission, four a reduction of tumour mass <50% and three a progression of tumour growth. (90)Y-DOTATOC could be a powerful and promising new therapeutic agent for anti-cancer treatment - at least in terms of an adjuvant starting point of the disease. However, problems with toxicity have to be solved. Evaluation of the effect of amino acid infusions (e.g. Hartmann-Hepa 8% solution) during (90)Y-DOTATOC treatments with the aim of reducing renal toxicity is ongoing.
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PMID:Yttrium-90 DOTATOC: first clinical results. 1055 85

Hb Peterborough [beta111(G13)Val-->Phe], an unstable hemoglobin variant with low oxygen affinity, was first described in two patients of Italian origin. This paper reports the first observation of this variant in Campania, Southern Italy, in two unrelated patients suffering from mild anemia. The variant was separated from Hb A by cation exchange chromatography on a high performance liquid chromatographic system with an automated procedure that might be useful for diagnostic purposes. The amino acid replacement, Val-Phe at [beta111, was assessed by tandem electrospray mass spectrometry analysis, and the corresponding DNA mutation was established as G-->T at the first position of codon 111 (GTC-TTC) by polymerase chain reaction amplification techniques. A family study showed that the two original carriers of Hb Peterborough were members of the same family as the proband examined in this study. This finding, and the presence of a second unrelated family carrying Hb Peterborough in Campania, strongly suggests that the DNA mutation associated with this variant originated in Southern Italy.
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PMID:The mutation associated with Hb Peterborough [beta111(G13)Val-->Phe] originated from Southern Italy. 1097 42

Thymic tumours are rare neoplasms which generally follow a slow pattern of growth, showing their aggressiveness locally through the infiltration of adjacent organs and they rarely metastasise hematogenically. In the presence of locally advanced, metastatic or inoperable disease, combined strategies including chemotherapy, radiotherapy and surgery are now being evaluated. Scintigraphy with 111In DTPA-D-Phe 1 octreotide was used for the first time in a relevant series of patients with thymic tumour (13 cases) by our research group. The presence of somatostatin receptors (ss-R) assayed in vivo provided the rationale for the use of a treatment based on the octreotide analog in a patient with thymoma and aplasia of the erythroid series (pure red cell aplasia, PRCA) in whom a complete response for the tumour and the remission of anemia was obtained. The efficacy of this treatment was confirmed by our series of patients with chemoresistant thymic tumour and by national and international confirmations. These data, ranging from in vivo diagnosis to treatment and the in vitro study of receptor expression, confirm that somatostatin plays a major role in thymic tumours.
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PMID:[Thymoma and somatostatin analogs. Biology, diagnostic and clinical practice]. 1175 43

We investigated the interrelationships between behavior and serum amino acid concentrations in iron-deficient anemic rats. Concentrations of proline, alanine, glycine, and phenylalanine in serum samples were significantly higher than those in rats fed a normal diet, while serum threonine, glutamic acid, and valine levels were significantly lower. Activities of locomotion, rearing, hole-poking, and grooming, determined by using a hole board apparatus, were significantly reduced in anemic rats. The supplementation of inorganic iron and amino acids proline, arginine, or glutamic acid to the normal diet lead to the recovery of normal behavior. Proline enhanced a significant increase in the number of red blood cells and hemoglobin by the supplementation of iron alone. We propose that the combination of amino acid (especially proline) and inorganic iron might lead to an improvement in behavioral disorders caused by iron-deficient anemia.
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PMID:Co-administration of proline and inorganic iron enhance the improvement of behavioral and hematological function of iron-deficient anemic rats. 1288 90

We describe a novel missense mutation of ceruloplasmin in a patient with aceruloplasminaemia causing the replacement of a neutral amino acid (phenylalanine) with a polar one (serine) at position 198, probably leading to abnormal folding and secretion of the protein. The patient showed mild microcytic anaemia, mild hepatic iron overload, and marked brain iron overload. Six months of therapy with deferiprone was ineffective in removing iron from the tissues. Deferoxamine was more efficient in removing excess iron from the liver but aggravated the disease related anaemia. After more than one year of chelation treatment, the brain magnetic resonance imaging signal did not change. Overall, these findings indicate that treatment of iron overload in aceruloplasminaemia is a difficult challenge and that new iron chelators, more efficient in crossing the blood-brain barrier, are needed.
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PMID:Iron chelation therapy in aceruloplasminaemia: study of a patient with a novel missense mutation. 1508 97

Manipulation of the mouse genome has emerged as an important approach for studying gene function and establishing human disease models. In this study, the mouse mutants were generated through N-ethyl-N-nitrosourea (ENU)-induced mutagenesis in C57BL/6J mice. The screening for dominant mutations yielded several mice with fur color abnormalities. One of them causes a phenotype similar to that shown by dominant-white spotting (W) allele mutants. This strain was named Wads because the homozygous mutant mice are white color, anemic, deaf, and sterile. The new mutation was mapped to 42 cM on chromosome five, where proto-oncogene c-kit resides. Sequence analysis of c-kit cDNA from Wads(m/m) revealed a unique T-to-C transition mutation that resulted in Phe-to-Ser substitution at amino acid 856 within a highly conserved tyrosine kinase domain. Compared with other c-kit mutants, Wads may present a novel loss-of-function or hypomorphic mutation. In addition to the examination of adult phenotypes in hearing loss, anemia, and mast cell deficiency, we also detected some early developmental defects during germ cell differentiation in the testis and ovary of neonatal Wads(m/m) mice. Therefore, the Wads mutant may serve as a new disease model of human piebaldism, anemia, deafness, sterility, and mast cell diseases.
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PMID:Identification of a novel point mutation of mouse proto-oncogene c-kit through N-ethyl-N-nitrosourea mutagenesis. 1573 17


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