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)

Chromosomal rearrangements of the 11p15 locus have been identified in hematopoietic malignancies, resulting in translocations involving the N-terminal portion of the nucleoporin gene NUP98. Fifteen different fusion partner genes have been identified for NUP98, and more than one half of these are homeobox transcription factors. By contrast, the NUP98 fusion partner in t(11;20) is Topoisomerase I (TOP1), a catalytic enzyme recognized for its key role in relaxing supercoiled DNA. We now show that retrovirally engineered expression of NUP98-TOP1 in murine bone marrow confers a potent in vitro growth advantage and a block in differentiation in hematopoietic precursors, evidenced by a competitive growth advantage in liquid culture, increased replating efficient of colony-forming cells (CFCs), and a marked increase in spleen colony-forming cell output. Moreover, in a murine bone marrow transplantation model, NUP98-TOP1 expression led to a lethal, transplantable leukemia characterized by extremely high white cell counts, splenomegaly, and mild anemia. Strikingly, a mutation to a TOP1 site to inactivate the isomerase activity essentially left unaltered the growth-promoting and leukemogenic effects of NUP98-TOP1. These findings, together with similar biologic effects reported for NUP98-HOX fusions, suggest unexpected, overlapping functions of NUP98 fusion genes, perhaps related to common DNA binding properties.
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PMID:NUP98-topoisomerase I acute myeloid leukemia-associated fusion gene has potent leukemogenic activities independent of an engineered catalytic site mutation. 1510 Jan 57

A 79-year-old woman presented with an obstructed femoral hernia and had a wedge resection of the small intestine. Post-operatively she developed wound dehiscence and spent 3 days in the adult critical care unit. Good recovery followed and she was allowed home after 2 months in hospital. Six months later she presented with anaemia, neutropenia and a very low serum copper concentration. Review of her notes revealed that she had been given oral zinc therapy while in the critical care unit and this treatment had been continued on discharge from hospital. Serum copper, haemoglobin and white cell count recovered after oral zinc was discontinued. Oral zinc treatment can lead to symptomatic copper deficiency in susceptible patients.
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PMID:Iatrogenic copper deficiency causing anaemia and neutropenia. 1533 96

Increased systemic inflammation and an impaired immune response are features of adult chronic renal failure (CRF). These patients have increased rates of infection, cardiovascular disease, anemia, and malnutrition. We measured inflammatory and immunological markers in a group of children with pre-dialytic CRF. No prior studies have explored these markers even though children with non-dialysed CRF exhibit similar complications to those seen in adults with CRF. Blood was collected from children with mild, moderate, or severe CRF and an age-matched control group. Functional leukocyte subsets were determined using flow cytometry. Circulating levels of interleukin (IL)-1beta, IL-6, IL-8, IL-12, IL-10, and tumor necrosis factor-alpha were measured using a flow cytometric bead assay. Children with severe CRF showed significantly reduced total white cell count and absolute neutrophil and lymphocyte counts. Absolute numbers of CD3+/CD45RO+ memory T cells and CD3+/CD45RO+/CD62L+ memory Th2 cells were significantly reduced in all CRF groups versus controls. Children with severe CRF showed increased CD11b expression on neutrophils and monocytes. Some patients showed increases in pro-inflammatory cytokines that were not related to their level of residual renal function. As CD11b expression mediates leukocyte adhesion to vascular endothelium, upregulation may contribute to the increased endothelial dysfunction observed in children with CRF. L-selectin mediates extravasation of leukocytes into tissue and homing of peripheral blood lymphocytes to lymph nodes. The reduction in L-selectin may inhibit these actions and predispose patients to increased infection later in life. This is the first study to comprehensively investigate leukocyte functional molecules and inflammatory cytokine profiles in children with pre-dialytic CRF and provides new immunological evidence for the clinical manifestations associated with the disease.
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PMID:Changes in leukocyte subsets: clinical implications for children with chronic renal failure. 1562 18

Pure red cell aplasia (PRCA) is a rare haematological condition that is characterized by severe aregenerative anaemia due to an almost complete cessation of red blood cell production. While antibody-mediated PRCA was extremely rare before 1998, the incidence of this disorder increased sharply after 1998 in patients receiving subcutaneous epoetin alfa produced by Ortho-Biotech and marketed outside the USA. The diagnosis of antibody-mediated PRCA relies mostly on the results of bone marrow biopsy or aspirate, which shows an absence of erythroid precursors and/or red cell maturation arrest while counts of white cell and platelet precursors are normal, and on the identification of circulating anti-erythropoietin antibodies. Retrospective analysis of PRCA cases has shown that immunosuppressive therapy can induce a disappearance of anti-erythropoietin antibodies in most patients. Eur J Clin Invest 2005; 35 (Suppl. 3): 95-99.
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PMID:Erythropoietin-induced, antibody-mediated pure red cell aplasia. 1628 65

Studies of renal transplantation utilizing trough plasma level monitoring of mycophenolic acid (MPA) have shown inconsistent associations with toxicity and rejection. In this study, 5600 12-h trough MPA samples from 121 renal transplant recipients immunosuppressed with mycophenolate mofetil (MMF) and tacrolimus in a steroid sparing protocol (steroids for 7 days only) were sequentially analyzed. Higher MPA levels were associated with lower hemoglobin concentrations and anemia (hemoglobin <10 g/dL). Similarly, higher MPA levels were associated with lower total white cell counts and an increased incidence of leucopenia (total white cell count <4.0 x 10(9)/L). Hypoalbuminemia and renal impairment were also associated with hemotoxicity. MMF-associated diarrhea and viral infection were associated with higher MPA levels. Conversely, biopsy-proven acute rejection within the first month post-transplantation was associated with lower MPA levels. Anti-CD25 antibody induction was also associated with reduced rejection rates. No association was seen between MPA levels and platelet count, thrombocytopenia or bacterial infection. An MPA level of 1.60 mg/L early post-transplantation best discriminated patients with and without rejection, and an MPA level of 2.75 mg/L best discriminated patients with and without toxicity later post-transplantation.
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PMID:Mycophenolic acid 12-h trough level monitoring in renal transplantation: association with acute rejection and toxicity. 1643 66

The aim of this audit was to assess the yield of a selection of laboratory tests as part of the clinical assessment of the fatigued athlete. Clinical charts and blood test results of fifty consecutive athletes who presented with the primary complaint of fatigue were retrospectively reviewed. Blood tests results reviewed were: haematology (haemoglobin, red cell count, mean cell volume, mean cell haemoglobin content, platelets, white cell count, differential white cell count); erythrocyte sedimentation rate; serum biochemistry (urea, creatinine, electrolytes, urate, glucose, liver function tests, albumin, globulin); blood iron status (serum iron, total iron binding capacity, percent transferring saturation, and ferritin concentration); thyroid stimulating hormone; and immune measures (Epstein-Barr virus serology, cytomegalovirus serology). We identified only 3 abnormal results that contributed to the diagnosis of medical disease as a cause for fatigue. Laboratory testing identified 2 fatigued female athletes with serum ferritin concentration between 15 microg L(-1) and 20 microg L(-1) plus two of the other criteria of iron concentration (serum iron <10 micromol L(-1), iron binding capacity > 68 micromol L(-1), or transferrin saturation <15%). We concluded that the yield from a selection of blood tests investigating fatigued athletes was low. Future study is needed to further define the role of laboratory testing and to study whether low iron stores in the absence of anaemia is related to symptoms in fatigued athletes.
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PMID:An audit of clinically relevant abnormal laboratory parameters investigating athletes with persistent symptoms of fatigue. 1733 43

Spirocerca lupi is a nematode infesting the canine oesophagus, where it induces the formation of a nodule that may transform into a malignant sarcoma. The current, retrospective study compared the clinical presentation, haematology, serum albumin and globulin and radiology of benign cases (n=31) and malignant cases (n=31) of spirocercosis. Dogs with spirocercosis-induced sarcoma were significantly older (6.4+/-1.91 years) than benign cases (4.93+/-2.87). In the malignant cases there were significantly (p=0.03) more sterilized females (10/31) and fewer intact males (4/31) compared to 2/31 and 13/31, respectively, in the benign cases. Hypertrophic osteopathy was observed in 38.7% of malignant cases and in none of the benign cases (p=0.0002). Common clinical signs included weight loss, regurgitation, anorexia, pyrexia (T>or=39.5 degrees ), respiratory complications and salivation but did not differ in prevalence between groups. On haematology, the malignant group had significantly (p<0.05) lower haematocrit (0.34+/-0.08 vs. 0.41+/-0.07) and higher white cell count (31.6+/-27.83 vs. 17.71+/-13.18 x 10(3)microl(-1)), mature neutrophil count (26.06+/-26.08 vs. 12.23+/-9.96 x 10(3)microl(-1)) and thrombocyte count (493.15+/-151.61 vs. 313.27+/-128.54 x 10(9)microl(-1)). There were no differences in the mean corpuscular volume and immature neutrophil count. On radiology, the mass length was not significantly different, but the height and the width of the malignant masses were significantly larger (62.59+/-15.15 mm and 73.93+/-20.94 mm) compared to the benign group (46.43+/-23.62 and 49.29+/-25.56, respectively). Spondylitis was more prevalent in the malignant group (67.86% vs. 38.46%, p=0.03). Examining secondary pulmonary changes revealed significantly higher prevalence of bronchial displacement in the malignant group (52% vs. 17%, p=0.008). Hypertrophic osteopathy appeared to be a very specific but relatively rare (poor sensitivity) marker of malignancy. Female gender, anaemia, leukocytosis, thrombocytosis, spondylitis and bronchial displacement are significantly more common in malignant cases, but appear in benign cases as well. However, if found together in a specific case, they should increase the index of suspicion for malignancy in a diagnosed spirocercosis case.
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PMID:Clinical differentiation between dogs with benign and malignant spirocercosis. 1853 58

We have investigated the pathogenicity of tsetse (Glossina pallidipes)-transmitted cloned strains of Trypanosoma brucei rhodesiense in vervet monkeys. Tsetse flies were confirmed to have mature trypanosome infections by xenodiagnosis, after which nine monkeys were infected via the bite of a single infected fly. Chancres developed in five of the nine (55.6%) monkeys within 4 to 8 days post infection (dpi). All nine individuals were successfully infected, with a median pre-patent period of 4 (range = 4-10) days, indicating that trypanosomes migrated from the site of fly bite to the systemic circulation rapidly and independently of the development of the chancre. The time lag to detection of parasites in cerebrospinal fluid (CSF) was a median 16 (range = 8-40) days, marking the onset of central nervous system (CNS, late) stage disease. Subsequently, CSF white cell numbers increased above the pre-infection median count of 2 (range = 0-9) cells/microl, with a positive linear association between their numbers and that of CSF trypanosomes. Haematological changes showed that the monkeys experienced an early microcytic-hypochromic anaemia and severe progressive thrombocytopaenia. Despite a 3-fold increase in granulocyte numbers by 4 dpi, leucopaenia occurred early (8 dpi) in the monkey infection, determined mainly by reductions in lymphocyte numbers. Terminally, leucocytosis was observed in three of nine (33%) individuals. The duration of infection was a median of 68 (range = 22-120) days. Strain and individual differences were observed in the severity of the clinical and clinical pathology findings, with two strains (KETRI 3741 and 3801) producing a more acute disease than the other two (KETRI 3804 and 3928). The study shows that the fly-transmitted model accurately mimics the human disease and is therefore a suitable gateway to understanding human African trypanosomiasis (HAT; sleeping sickness).
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PMID:Trypanosoma brucei rhodesiense transmitted by a single tsetse fly bite in vervet monkeys as a model of human African trypanosomiasis. 1884 31

Thalassemia is a hereditary anemia resulting from defect in hemoglobin production. Beta thalassemia is due to impaired production of beta globin chains, leading to a relative excess of alpha globin chains. The term beta thalassemia minor is used to describe heterozygotes, who carry one normal beta globin allele and one beta thalassemic allele. The vast majority of these patients are asymptomatic. However, a variety of renal tubular abnormalities including hypercalciuria, hypo-magnesemia with renal magnesium wasting, decreased tubular absorption of phosphorus, hypo-uricemia with renal uric acid wasting, renal glycosuria and tubular proteinuria have been described even in patients with beta thalassemia minor. We here in report a 24-year old female patient who was found to have thalassemia minor and nephrocalcinosis with evidence of renal tubular dysfunction. Investigations revealed normal renal function, hypercalciuria, reduced tubular reabsorption of phosphorus, hypomagnesemia and renal magnesium wasting. Screening for aminoaciduria was found to be negative. An acid loading test revealed normal urinary acidification. Ultrasonogram of the abdomen revealed nephrocalcinosis and splenomegaly. Detailed work up for anemia showed normal white cell and platelet count while peripheral smear showed microcytic hypochromic anemia with few target cells. Hemoglobin electrophoresis revealed hemoglobin A of 92%, hemoglobin A2 of 6.2% and hemo-globin F of 1.8% consistent with beta thalassemia minor. Her parental screening was normal. A diagnosis of beta thalassemia minor with renal tubular dysfunction was made and the patient was started on thiazide diuretics to reduce hypercalciuria and advised regular follow-up.
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PMID:Renal tubular dysfunction with nephrocalcinosis in a patient with beta thalassemia minor. 1897 85

Based on the rewiew of the literature and own clinical observations, we presented examples of the most common pediatric onco-hematologic malignancies, that are manifested early by osteoarticular complaints. When these complaints predominate in the clinical presentation, they lead the diagnosis towards nonmalignant conditions, that are most common cause of such symptoms in children, like injuries, nonspecific reactive arthritis or inflammatory connective tissue diseases. However, in acute lymphoblastic leukaemia, the most prevalent childhood malignancy, bone and joint pains are present early in 40-60% of cases and they frequently anticipate any abnormalities in complete blood counts. Findings reported in the literature and own observations indicate that these complaints correlate with: lower white cell counts, lower percentage of blast cells in the peripheral blood and lower incidence of organomegaly - that may delay the decision of bone marrow aspiration. In our study we have also presented 4 cases of other malignancies in children, who were complaining of the osteoarticular pains, that limited they activity, long time before the beginning of treatment in Department of Oncology and Pediatric Hematology of University's Pediatric Hospital in Cracow. Long-lasting and intensive osteoarticular complains, that restraint normal activity and do not resolve during rest, spinal compression symptoms, coexisting adenopathy, hepatosplenomegaly, weight loss, change of behaviour, unexplicained fever must be recognized as specific "red flags". Oncologic vigilance must be inspired by discreet hematological abnormalites (like increased anemia, lower white cell counts with lymphocytosis, mild thrombocytopenia) -that indicate bone marrow infiltration, as well as high erythrocyte sedimentation rate, accompanied by moderately elevated C-reactive protein - characteristic for malignancy. Basic and commonly accessible radiological imaging may provide valuable information, because it can reveal tumors, osteolytic lesions or destruction of bone architecture. Laboratory tests of lactate dehydrogenase (LDH) and uric acid level, often raised in malignancies are also helpful. The aim of this study was to focus the attention of pediatricians to the necessity of including malignancy in the differential diagnosis of intensive or unexplained osteoarticular complaints.
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PMID:[Osteoarticular pains as early manifestation of malignancies in children]. 1948 54


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