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)

Malaria in pregnancy is responsible for maternal anaemia, low-birth-weight babies and infant deaths. Plasmodium falciparum infected erythrocytes are thought to cause placental pathology by adhering to host receptors such as chondroitin sulphate A (CSA). CSA binding infected erythrocytes also bind IgM natural antibodies from normal human serum, a process that may facilitate placental adhesion or promote immune evasion. The parasite ligands that mediate placental adhesion are thought to be members of the variant erythrocyte surface antigen family P. falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the var genes. Two var gene sub-families, var1CSA and var2CSA, have been identified as parasite CSA binding ligands and are leading candidates for a vaccine to prevent pregnancy-associated malaria. We investigated whether these two var gene subfamilies implicated in CSA binding are also the molecules responsible for IgM natural antibody binding. By heterologous expression of domains in COS-7 cells, we found that both var1CSA and var2CSA PfEMP1 variants bound IgM, and in both cases the binding region was a DBL epsilon domain occurring proximal to the membrane. None of the domains from a control non-IgM-binding parasite (R29) bound IgM when expressed in COS-7 cells. These results show that PfEMP1 is a parasite ligand for non-immune IgM and are the first demonstration of a specific adhesive function for PfEMP1 epsilon type domains.
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PMID:Identification of Plasmodium falciparum var1CSA and var2CSA domains that bind IgM natural antibodies. 1644 68

Antibodies to variant surface antigen have been implicated as mediators of malaria immunity in studies measuring immunoglobulin G (IgG) binding to infected erythrocytes. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is an important target for these antibodies, but no study has directly linked the presence of PfEMP1 antibodies in children to protection. We measured plasma IgG levels to the cysteine-rich interdomain region 1alpha (CIDR1alpha) of VAR4 (VAR4-CIDR1alpha), a member of a semiconserved PfEMP1 subfamily, by enzyme-linked immunosorbent assay in 561 Tanzanian individuals, who were monitored clinically for 7 months. The participants resided in Mkokola (a high-transmission village where malaria is holoendemic) or Kwamasimba (a moderate-transmission village). For comparison, plasma IgG levels to two merozoite surface protein 1 (MSP1) constructs, MSP1-19 and MSP1 block 2, and a control CIDR1 domain were measured. VAR4-CIDR1alpha antibodies were acquired at an earlier age in Mkokola than in Kwamasimba, but after the age of 10 years the levels were comparable in the two villages. After controlling for age and other covariates, the risk of having anemia at enrollment was reduced in VAR4-CIDR1alpha responders for Mkokola (adjusted odds ratio [AOR], 0.49; 95% confidence interval [CI], 0.29 to 0.88; P = 0.016) and Kwamasimba (AOR, 0.33; 95% CI, 0.16 to 0.68; P = 0.003) villages. The risk of developing malaria fever was reduced among individuals with a measurable VAR4-CIDR1alpha response from Mkokola village (AOR, 0.51; 95% CI, 0.29 to 0.89; P = 0.018) but not in Kwamasimba. Antibody levels to the MSP1 constructs and the control CIDR1alpha domain were not associated with morbidity protection. These data strengthen the concept of developing vaccines based on PfEMP1.
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PMID:Levels of plasma immunoglobulin G with specificity against the cysteine-rich interdomain regions of a semiconserved Plasmodium falciparum erythrocyte membrane protein 1, VAR4, predict protection against malarial anemia and febrile episodes. 1662 25

A 21-year-old woman of Romany origin, in the third trimester of her fourth pregnancy, was admitted to the hospital because of a generalized erythematous and pustular eruption and desquamation involving her face, neck, trunk, and extremities. The skin changes were accompanied by fever (100.4 degrees F [38 degrees C]) and malaise. The patient was convinced that the dermatitis was induced by the consumption of "spoilt" pork sausage (bad smell, changed taste) approximately 24 hours earlier. Clinical examination revealed a woman with phototype III skin, black eyes, and black hair, in good general health. Widespread, symmetrical, moderately intense erythema and isolated or coalescing targetoid lesions studded with discrete, pinhead-sized, nonfollicular pustules in the center or at the periphery were distributed over her face, trunk, groins, and upper and lower extremities (Figures 1). On the neck and abdomen, lamellar desquamation was observed (Figure 2). Palms, soles, scalp, mucous membranes, hair, and nails were not affected. Nikolsky's sign was negative. The patient complained of very slight skin burning and itching. The pregnancy was proceeding without any complications and her obstetric status was normal. The woman had neither any accompanying diseases, nor previous personal or family history of psoriasis, nor any known allergies. She had taken no systemic medication (not even vitamins). She had three pregnancies; two ended with the delivery of healthy babies and one of them was aborted at her will. Laboratory studies revealed leukocytosis (13.2 x 109/L), neutrophilia (8 x 109/L), anemia (hemoglobin, 108 g/L), and an elevated erythrocyte sedimentation rate (68-110 mm/h). The results from the following investigations were normal: urinalysis, renal and hepatic function, serum albumin, Ca, Na, K, aspartate aminotransferase titer, cryoprotein, hepatitis B surface antigen, and serum markers for syphilis. Bacterial and fungal cultures of pustular content were sterile. A skin biopsy specimen of lesional skin revealed subcorneal pustules containing leukocytes and necrotic keratinocytes and a mixed perivascular inflammatory infiltrate with isolated eosinophils in the dermis (Figure 3). The patient was treated with systemic methylprednisolone in gradually reduced doses, fluocinonide cream 0.05%, and emollients. As a result, her fever disappeared and her erythema faded. Frequent obstetric examination and cardiotocography were normal and showed no evidence of placental insufficiency. At 40 weeks' gestation, the patient spontaneously gave birth without any complications to a healthy boy. She was discharged with complete resolution of the skin lesions, preceded by massive desquamation of the epidermis. The 1-year follow-up of the patient revealed no relapses or new pustular eruptions.
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PMID:Food-induced acute generalized exanthematous pustulosis in a pregnant woman. 1685 16

The case-control study was conducted among addicts in Alexandria to determine the different health problems among them, as well as to study the correlation between addiction and these problems. One hundred drug addicts and eighty apparently healthy controls were included in this study. The whole sample was subjected to the following: filling a predesigned questionnaire sheet, clinical and electrocardiogram (ECG) examination, measurements of Body Mass Index (BMI), complete blood picture and antistreptolysin O titre (ASO), testing for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti HBc), skin scrapings from superficial fungal lesions in addition to complete urine and stool examination. The results revealed that chest rhonchi, hepatomegaly, central nervous system (CNS) abnormalities, skin lesions lymphadenopathy, underweight and anaemia were significantly higher among addicts than the controls. Hepatitis B virus (HBV) exposure and HBsAg seropositivity were found 48.0% and 21.0%, respectively among addicts compared to 26.3% and 5.0%, respectively among the controls. The intravenous injections and tattooing were the most risky routes for HBV infection among addicts. A positive correlation was revealed between HBV exposure and both the duration and the number of daily injections. Chest X-ray suggestive of pulmonary tuberculosis were found in 7.0% of the addicts. Addiction potentiated the risk of fungal infection among low social class, but it had no effect on the relationship between anaemia and social class nor on that between loss of appetite and underweight.
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PMID:Health status assessment of drug addicts in Alexandria. 1721 25

Erythropoietin (Epo) is the main erythropoietic hormone. Recombinant human Epo (rHuEpo) is thus used in clinical practice for the treatment of anemia. Accumulating data reveals that Epo exerts pleiotropic activities. We have previously shown an anti-neoplastic activity of Epo in murine multiple myeloma (MM) models, and in MM patients. Our findings that this anti-neoplastic effect operates via CD8+ T lymphocytes led us to hypothesize that Epo possesses a wider range of immunomodulatory functions. Here we demonstrate the effect of Epo on B lymphocyte responses, focusing on three experimental models: (i) tumor-bearing mice, (5T2 MM mouse); (ii) antigen-injected healthy mice; and (iii) antigen-injected transgenic mice (tg6), overexpressing human Epo. In the MM model, despite bone marrow dysfunction, Epo-treated mice retained higher levels of endogenous polyclonal immunoglobulins, compared to their untreated controls. In both Epo-treated wild type and tg6 mice, Epo effect was manifested in the higher levels of splenocyte proliferative response induced in vitro by lipopolysaccharide. Furthermore, these mice had increased in vivo production of anti-dinitrophenyl (DNP) antibodies following immunization with DNP-keyhole limpet hemocyanin. Epo-treated mice showed an enhanced immune response also to the clinically relevant hepatitis B surface antigen. These findings suggest a potential novel use of rHuEpo as an immunomodulator.
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PMID:Erythropoietin enhances immune responses in mice. 1750 33

The consequences of pregnancy-associated malaria on pregnant women (anaemia), their babies (birth weight reduction), and infants (increased morbidity and mortality) are well documented. Field observations during the last decade have underlined the key role of the interactions between P. falciparum variable surface antigens expressed on infected erythrocytes and a novel receptor: chondroitin sulfate A (CSA) for the placental sequestration of infected erythrocytes. Identification of a distinct P. folciparum erythrocyte membrane protein 1 (PfEMP1) variant, VAR2CSA, as the dominant variant surface antigen and as a clinically important target for protective immune response to pregnancyassociated malaria has raised hope for developing a new preventive strategy based on inducing these immune responses by vaccination. However, despite particular structure and interclonal conservation of VAR2CSA among other PfEMP1, significant challenges still exist concerning the development of a VAR2CSA-based vaccine with profound efficacy.
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PMID:Towards a vaccine against pregnancy-associated malaria. 1881 33

In areas of endemicity pregnancy-associated malaria is an important cause of maternal anemia, stillbirth, and delivery of low-birth-weight children. The syndrome is precipitated by the accumulation of Plasmodium falciparum-infected erythrocytes in the placenta, mediated through an interaction between a parasite protein expressed on erythrocytes named variant surface antigen 2-chondroitin sulfate A (VAR2CSA) and CSA on syncytiotrophoblasts. VAR2CSA is a large polymorphic protein consisting of six Duffy binding-like (DBL), domains and with current constraints on recombinant protein production it is not possible to produce entire VAR2CSA recombinant proteins. Furthermore, the presence of polymorphisms has raised the question of whether it is feasible to define VAR2CSA antigens eliciting broadly protective antibodies. Thus, the challenge for vaccine development is to define smaller parts of the molecule which induce antibodies that inhibit CSA binding of different parasite strains. In this study, we produced a large panel of VAR2CSA proteins and raised antibodies against these antigens. We show that antibodies against the DBL4 domain effectively inhibit parasite binding. As the inhibition was not limited to homologous parasite strains, it seems feasible to base a protective malaria vaccine on a single VAR2CSA DBL domain.
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PMID:Induction of adhesion-inhibitory antibodies against placental Plasmodium falciparum parasites by using single domains of VAR2CSA. 1930 13

End-stage renal disease has emerged as a major public health problem around the world. In recent decades, several important advances have been made in the therapy of hemodialysis (HD) with the introduction of international guidelines to ensure the delivery of optimum care to HD patients. An increased mortality risk in HD patients unable to meet six targets in different areas of HD practice has been reported by the Dialysis Outcomes and Practice Patterns Study investigators. In this retrospective study, we assessed the current practice patterns of care for HD patients in the Kaser El-Aini Nephrology and Dialysis Center in comparison with Dialysis Outcomes Quality Initiative Guidelines, European Best Practice Guidelines, Centers for Disease Control and Prevention guidelines for prevention of transmission of infections among HD patients, and American Association for Medical Instrumentation (AAMI) standards for dialysis water quality. The mean percent of urea reduction was 63 +/- 8.8% in prevalent HD patients. An arteriovenous fistula was the vascular access in 91% of prevalent HD patients, whereas a temporary catheter was used in 9% of cases mostly as a bridge till arteriovenous fistula creation/maturation. Bicarbonate was the base used in 80% of the cases. Ninty-seven percent patients had thrice-weekly sessions and 3% had two dialysis sessions/wk. The mean serum albumin was 4.19 +/- 0.39 g/dL; 66.66% of prevalent patients had serum albumin level >4 g/dL. The mean serum calcium was 8.66 +/- 1.4 mg/dL, phosphorus was 6.26 +/- 2.54 mg/dL, and approximately 60% of patients had a serum phosphorus level >5.5 mg/dL. The CaxPi product was higher than 55 in around 40% of the cases, and the parathyroid hormone level was in the range of 150 to 300 pg/mL in around 10% of prevalent patients. The mean hemoglobin was 9.23 +/- 7.18 g/dL in prevalent cases; around 70% of cases had a hemoglobin level <11 g/dL. Iron deficiency was prevalent as 18% of patients, with serum ferritin <200 ng/L, and 34% had total serum test <20%. Seventy percent of the patients were hepatitis C virus positive and 4% were hepatitis B surface antigen positive, and all were negative for the human immunodeficiency virus serological test. Dialysis water was monitored regularly for chemical and bacterial contamination as recommended by the American Association for Medical Instrumentation, but an endotoxin assay is currently not included in the monitoring checklist. The annual mortality rate was 8% in 2007. The current audit revealed a reasonable quality of care for HD patients in the fields of vascular access care, dialysis adequacy, and nutrition areas. It also reveals the need for improving anemia management and control of hyperphosphatemia with dietary counseling and more frequent dialysis. To fully meet the guideline targets, each patient should be treated in an individualized way with more counseling, nutritional education, and individualized dialysis prescription. Besides, the unit needs to adopt primary and secondary intervention strategies to prevent and promptly correct any deviation from the desired targets.
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PMID:Quality of care assessment and adherence to the international guidelines considering dialysis, water treatment, and protection against transmission of infections in university hospital-based dialysis units in Cairo, Egypt. 1975 97

Pregnant women have a higher risk of malaria compared to non-pregnant women. This review provides an update on knowledge acquired since 2000 on P. falciparum and P.vivax infections in pregnancy. Maternal risk factors for malaria in pregnancy (MiP) include low maternal age, low parity, and low gestational age. The main effects of MIP include maternal anaemia, low birth weight (LBW), preterm delivery and increased infant and maternal mortality.P. falciparum infected erythrocytes sequester in the placenta by expressing surface antigens, mainly variant surface antigen (VAR2CSA), that bind to specific receptors, mainly chondroitin sulphate A. In stable transmission settings, the higher malaria risk in primigravidae can be explained by the non-recognition of these surface antigens by the immune system. Recently, placental sequestration has been described also for P.vivax infections. The mechanism of preterm delivery and intrauterine growth retardation is not completely understood, but fever (preterm delivery), anaemia, and high cytokines levels have been implicated.Clinical suspicion of MiP should be confirmed by parasitological diagnosis. The sensitivity of microscopy, with placenta histology as the gold standard, is 60% and 45% for peripheral and placental falciparum infections in African women, respectively. Compared to microscopy, RDTs have a lower sensitivity though when the quality of microscopy is low RDTs may be more reliable. Insecticide treated nets (ITN) and intermittent preventive treatment in pregnancy (IPTp) are recommended for the prevention of MiP in stable transmission settings. ITNs have been shown to reduce malaria infection and adverse pregnancy outcomes by 28-47%. Although resistance is a concern, SP has been shown to be equivalent to MQ and AQ for IPTp. For the treatment of uncomplicated malaria during the first trimester, quinine plus clindamycin for 7 days is the first line treatment and artesunate plus clindamycin for 7 days is indicated if this treatment fails; in the 2(nd) and 3(rd) trimester first line treatment is an artemisinin-based combination therapy (ACT) known to be effective in the region or artesunate and clindamycin for 7 days or quinine and clindamycin. For severe malaria, in the second and third trimester parenteral artesunate is preferred over quinine. In the first trimester, both artesunate and quinine (parenteral) may be considered as options. Nevertheless, treatment should not be delayed and should be started immediately with the most readily available drug.
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PMID:Malaria in pregnancy. 2335 23

We studied the dialysis practice-patterns with regard to various aspects of chronic kidney disease (CKD) stage 5D, like anemia, mineral bone disease, vaccination, hospitalization, hypertension and cost of therapy. Four hundred and sixty-four adult hemodialysis (HD) patients from various dialysis centers of Mumbai were included in the study. The mean age of the study patients was 47.2 years. Temporary dialysis catheters were the most common initial vascular access. Thirteen percent of prevalent HD patients were on temporary catheters; 33% of patients had history of failure of arterio-venous fistula. The most common cause of failure was access thrombosis. About 75% of the patients had hemoglobin <11 g/dL and 35% had uncontrolled blood pressure. The prevalence of positive hepatitis B surface antigen and anti-hepatitis C virus antibody was 6% and 2%, respectively. The average cost of HD treatment was approximately 6100 Indian rupees (about US $100). HD is helpful in treating many of the clinical manifestations of CKD and postpones otherwise imminent death. However, dialysis treatment is no panacea to renal failure; HD patients have higher hospitalization rates and lower quality of life than the general population. The therapy itself brings with it a unique set of problems, such as vascular access-related complications, which cause significant mortality and morbidity. This study was a study of the current HD practices. The primary goal of this cross-sectional observational study is to understand dialysis practices and obtain data that can be used to improve care in the future.
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PMID:A cross-sectional study of dialysis practice-patterns in patients with chronic kidney disease on maintenance hemodialysis. 2635 90


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