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 clinical heterogeneity and the role of red cell membrane protein band 7 in membrane transport were studied in 44 patients with hereditary stomatocytosis with normal red cell membrane lipids. These patients were arbitrarily categorized into three phenotypes, based on the extent of sodium influx: hereditary stomatocytosis Type I: with markedly increased Na influx (8.90 +/- 3.39 mmol/lRBC/h); Type II: with moderately increased Na influx (2.10 +/- 0.79) and Type III with normal Na influx (1.31 +/- 0.13). The three groups of patients were compared with normal controls (1.29 +/- 0.14). The extent of anaemia and jaundice was almost identical in the three groups in the presence of nearly the same degree of stomatocytosis (I: 54.8 +/- 10.7%, II: 38.8 +/- 12.8, and III: 40.2 +/- 10.8). Approximately one third of the cases (14/44) with hereditary stomatocytosis showed no overt haemolysis even with marked stomatocytosis. Cell hydration was abnormal in Type I (MCV 119.6 +/- 8.5 fl, MCHC 29.3 +/- 1.8%) but normal in Types II and III (MCV 98.2 +/- 11.7, 94.1 +/- 8.5; MCHC 34.4 +/- 2.1, 34.5 +/- 2.2). These results indicate that there was no correlation between the extent of Na influx and either the degree of stomatocytosis or the extent of overt haemolysis. The role of band 7 in membrane transport was also studied. Three components (30 kD, 28 kD and 26 kD polypeptides) of band 7 were analysed by SDS-PAGE and NEPHGE/SDS-PAGE, and the content of these polypeptides were expressed as the ratio to band 5. The 30 kDa polypeptide in the three groups was nearly identical to that in normal controls (12.3 +/- 4.0), except for non-haemolysing patients in Type II. The 28 kD peptide was also decreased in five out of nine cases of Type II (25.7 +/- 5.6) as compared with normal controls (32.9 +/- 3.6) and cases of Type I (35.8 +/- 2.8) and Type III (32.7 +/- 2.9). No deficiency of this peptide was noted in Type I patients. No correlation was observed between the content of the 28 kD polypeptide and Na influx (r = 0.416), but the 26 kD polypeptide tended to be elevated in cases with overt haemolysis. These results suggest that band 7 may not be essentially involved in the formation of stomatocytic changes, although the presence of subtle defects in band 7 structure and function may not be ruled out. The present findings provide an important starting point to initiate further extensive investigations.
 ...
PMID:Hereditary stomatocytosis: phenotypical expression of sodium transport and band 7 peptides in 44 cases. 141 88

A 23-year-old woman experienced six distinct episodes of severe combined neutropenia and thrombocytopenia. At least one of the episodes was accompanied by hemodialysis-requiring acute renal failure and fragmentation hemolysis (hemolytic uremic syndrome [HUS]). In retrospect, all episodes were probably associated with the ingestion of quinine. Quinine-dependent antibodies to platelets, neutrophils, T lymphocytes, and red blood cells (RBCs) were detected in the patient's serum. By a monoclonal antibody antigen capture assay, the patient's serum contained IgG antibodies, which in the presence, but not absence, of quinine reacted with platelet glycoprotein (GP) complexes Ib/IX and IIb/IIIa, but not Ia/IIa. By immunoprecipitation assay, the serum, after addition of quinine, reacted strongly with an 85-Kd neutrophil membrane protein and weakly with 130- and 60-Kd moieties. Serum adsorbed with RBCs in the presence of quinine continued to react with platelets and neutrophils, and serum that was absorbed with platelets continued to react with neutrophils and RBCs, indicating that the antigenic targets were different on platelets, neutrophils, and RBCs. Since platelets and endothelial cells share some antigens, we tested patient serum for antibodies to human umbilical vein endothelial cells (HUVEC); no quinine-dependent antibodies to HUVEC were detected. However, her quinine-dependent antibodies not only bound to platelets and neutrophils, but also activated neutrophils. Thus, the patient's serum with quinine aggregated neutrophils, but neither agent alone caused activation. Moreover, the patient's serum with quinine (but not without) augmented the adherence of neutrophils to HUVEC. Treatment of the patient's serum with staphylococcal protein A removed the quinine neutrophil aggregation cofactor, suggesting it was due to IgG. In both neutrophil aggregation and adherence assays, decomplementation of the patient's serum markedly blunted its effect. Furthermore, the patient's serum failed to aggregate formalin-inactivated neutrophils, suggesting neutrophil activation, probably by activated complement, was necessary for aggregation and adhesivity to endothelium. We conclude that our patient's neutropenia, thrombocytopenia, lymphopenia, and anemia were due to quinine-dependent antibodies, and that these antibodies recognized epitopes that were different in the three target cell populations. We further suggest that HUS was likely secondary to the activation and adhesion of neutrophils to endothelium.
 ...
PMID:Characterization of multiple quinine-dependent antibodies in a patient with episodic hemolytic uremic syndrome and immune agranulocytosis. 161 Oct 88

Chronic myelogenous leukaemia (CML) is a haematologic malignancy characterised by excessive growth of myeloid cells and their progenitors. Our studies show that there are several abnormalities in CML red blood cells. The proportion of spectrin dimers compared to tetramers extracted from membranes at 4 degrees C, under low ionic strength conditions, increased in CML erythrocytes. These also displayed abnormal thermal sensitivity (between 45 and 46 instead of 49 degrees C). Decreased spectrin tetramer formation observed in several hereditary anaemias has been associated with decreased red cell deformability leading to splenic sequestration. This could also be one of the causes of the severe anaemia observed in CML. Crosslinking with the bifunctional reagent, dimethyl adipimidate (8.6 A) showed significant organizational modification of not only spectrin, but other cytoskeletal components such as ankyrin, bands 4.2 and 5. Enhanced concanavalin A agglutinability of CML erythrocytes also suggests altered topographic distribution of a functionally important membrane protein, band 3.
 ...
PMID:Abnormal erythrocyte membrane cytoskeleton structure in chronic myelogenous leukaemia. 319 Nov 16

A new dominantly inherited dyserythropoietic anaemia is described. In the bone marrow, many of the nonspecific morphological characteristics described in congenital dyserythropoietic anaemias were seen; however, dysmorphic cells were rare. The acidified serum test was positive with one out of 17 sera tested; the negative sera included two that had haemolysed HEMPAS erythrocytes in the acid Ham test. Anti-i-agglutination was negative. No aberrations of red cell membrane protein glycosylation were observed. Serum cholesterol was low. Bilirubin conjugation was deficient but icterus was resolved by treatment with phenobarbital.
 ...
PMID:A new congenital dyserythropoietic anaemia. 334 87

We report an unusual case of congenital dyserythropoietic anaemia (CDA). The propositus is a 25-year-old gipsy female presenting with a recessively inherited haemolytic anaemia. The diagnosis of CDA was based on erythrokinetic data and the morphological appearance of the erythroid precursors. The direct assay of HEMPAS antigen was negative. In peripheral blood there were 15% dacryocytes. The red cell membrane protein pattern was dramatically altered, with four major aberrant bands. Band a (mol wt 86,000) was at the lower edge of band 3, band b (mol wt 82,000) was below band 3, band c (68,000) and band d (67,000) were below band 4.2. In addition, there was an array of aberrant minor bands below band d. Gel densitometric determinations and immunological characterization showed that these bands did not derive from any of the major components of the membrane. In fact, membrane proteins appeared normal in many respects, although periodic acid-Schiff staining revealed an apparent decrease of sialoglycoproteins. The major aberrant bands a, b and c occur in very low amounts in controls. These bands, as well as band d, also exist in normal cytosol and were strongly increased in the propositus.
 ...
PMID:Aberrant pattern of red cell membrane and cytosolic proteins in a case of congenital dyserythropoietic anaemia. 362 Mar 58

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

With the striking progress in analytic technology for detecting gene abnormalities, genetic analysis, such as polymerase chain reaction (PCR), has become a routine procedure in laboratory medicine. Consequently, the role of laboratory medicine in detecting genetic disease is increasing. However, in the process of genetic analysis maintaining consistency with clinical expression is necessary. In this symposium, the discussion includes the following items: (1) Genetic analysis of Maple Syrup Urine Disease (MSUD), (2) Analytic study of abnormal antithrombin III (TOYAMA), (3) Diagnostic procedures for anemia attributed to RBC membrane protein abnormality, (4) Genetic analysis of LDH-M subunit deficiency, (5) Development of a new prospect for hereditary hyperlipidemia, (6) Genetic analysis of hormone resistance syndromes: T3 receptor abnormality, and (7) Etiologic genetic analysis of pituitary cretinism. In general, DNA analysis in these cases can demonstrate wide variations in gene structural abnormalities. In MSUD, for instance, enzyme abnormalities, which occur in enzyme complex of various kinds include E1 alpha, beta, or E2. Currently, the cell fusion method, and PCR-SSCP method, miss-match PCR-DGGE method and so on are commonly used analytic methods. To sum up the issues discussed at this symposium, the most important function of genetic analysis is to clarify the relationship between the many clinical phenotypic expressions and the essential abnormality in the structure of the gene and/or function of the controlling proteins.
 ...
PMID:[A clue for discovery and recent progress in gene abnormalities]. 835 May 10

Experiments were undertaken to evaluate the type of protection conferred against Haemonchus contortus by immunising sheep with H11, a 'hidden' integral gut membrane protein isolated from this parasite. A serial kill experiment showed that worms began to be lost from immunised lambs between seven and 14 days after challenge with a single dose of larvae and adult female worms were more susceptible than male worms. Seven-day-old juveniles survived immunisation even though their intestinal cells became coated with sheep antibody. Immunisation was equally effective against both benzimidazole-resistant and susceptible strains of H contortus. When immunised lambs were subjected to a trickle infection, they were largely protected against the anaemia and egg output observed in the challenge controls. Moreover, they grew as fast and as efficiently as uninfected lambs fed on the same high protein diet and acquired a natural immunity during the course of the trickle infection.
 ...
PMID:Evaluation of aspects of the protection afforded to sheep immunised with a gut membrane protein of Haemonchus contortus. 837 1

Initial manifestation of malignant lymphoma in the adrenal gland is a rare event, and clinical and pathologic features are not fully understood. We conducted a nationwide study in Japan, and 20 patients with malignant lymphoma that showed initial and main manifestation in the adrenal gland were identified. Clinical and pathologic findings were summarized. In addition, the presence of the Epstein-Barr virus (EBV) genome in the tumor cells was examined by using polymerase chain reaction (PCR) and in situ hybridization (ISH), together with the immunohistochemical evaluation of the expression of latent membrane protein-1 (LMP-1). There were 13 men and seven women; their ages at admission ranged from 40 to 87 years (median, 65 yr). Fever, anemia, and elevation of lactic dehydrogenase levels were the common presenting findings. One patient had acquired immunodeficiency syndrome. Adrenal tumors were bilateral in 15 patients and unilateral (all in the left site) in five. Prognosis was very poor; all but two patients died within 1 year after admission. Histologically diffuse large cell type was the commonest type (14 specimens). Immunohistologically, 16 specimens were B-cell type, and one was T-cell type. Another three specimens showing no positive reaction for any antibodies were also judged as B-cell type on purely morphologic grounds. Prominent intravascular proliferation of tumor cells was found in five patients. PCR for EBV genomes gave positive results in five patients; the virus was subtyped as A in three patients and as B in two. The ISH provided positive signals in nine samples, including all five specimens positive for PCR. Four of the nine cases with detectable EBV by PCR and/or ISH expressed LMP-1. The present study shows that adrenal lymphoma is EBV associated and has a B-cell phenotype.
 ...
PMID:Malignant lymphoma of the adrenal gland: its possible correlation with the Epstein-Barr virus. 873 69

The association of Epstein-Barr virus (EBV) with smooth-muscle tumors was recently reported in the setting of acquired immunodeficiency syndrome (AIDS) and post-transplantation. We report a case of an EBV-associated smooth-muscle tumor arising in a post-transplant (PT) patient who previously was treated successfully for two EBV-associated PT large-cell lymphomas. A 4-year-old girl required cardiac transplantation for dilated cardiomyopathy when she was aged 23 months. Her PT regimen included cyclosporine, azothiaprine, and diltiazem. At 16 months PT, she presented with anemia, guaiac-positive stools, and an abdominal mass diagnosed as diffuse large-cell lymphoma of B-cell phenotype. Immunosuppressive therapy was reduced, and interferon and i.v. immunoglobulin were initiated. She rapidly developed signs of rejection, and a cardiac biopsy was performed, revealing grade IIIB rejection. Subsequently, immunosuppressive therapy increased. At 23 months PT, a biopsy was done of a large pelvic mass that was diagnosed as immunoblastic large-cell lymphoma. After treatment with chemotherapy and retinoic acid, the size of the mass markedly decreased. Follow-up computed tomography scan revealed multiple liver nodules. A needle biopsy of the liver showed a smooth-muscle tumor of indeterminate grade. Both the lymphomas and the smooth-muscle tumor contained EBV within > 95% of tumor cells by Epstein-Barr (EBER1) in situ hybridization, were of strain type A by Epstein-Barr nuclear antigen-2 (EBNA-2) polymerase chain reaction (PCR) and contained an identical 30 base-pair deletion (amino acids 346-355) of the latent membrane protein (LMP)-1 oncogene by PCR analysis. Notably, the initial large-cell lymphoma and the subsequent immunoblastic lymphoma each contained a unique p53 mutation, suggesting that they were distinct. These data suggest that the same virus contributed to the pathogenesis of both the malignant lymphomas and the smooth-muscle tumor.
 ...
PMID:Epstein-Barr virus (EBV)-associated smooth-muscle tumor arising in a post-transplant patient treated successfully for two PT-EBV-associated large-cell lymphomas. Case report. 894 45


1 2 3 4 5 6 Next >>