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1.
Mohsen A. F. El-Hazmi Hassan M. Bahakim Arjumand S. Warsy Abdulkarim Al-Momen Abdullah Al-Wazzan Ibrahim Al-Fawwaz Sameer Huraib Mohammad Harakati 《Molecular and cellular biochemistry》1993,124(1):17-22
Sickle cell anaemia (SCA) exhibits significant variations in clinical presentation in different populations for which several genetic factors including SCA-associated -and -thalassaemias, G-6-PD deficiency and elevated Hb F level have been implicated as possible ameliorating factors. Saudi Arabia is unique in that mild and severe forms of the disease occur at a high frequency. We investigated the G/A ratio and Hb F level and correlated these values with the severity of SCA. The results showed that Hb F level varies significantly in both groups of patients with no evident correlation with the mild clinical manifestations. However, G/A ratio correlated significantly with the disease severity where a high ratio was observed in patients with the mild and a low ratio in patients with the severe disease. The results are evaluated and discussed in the light of correlation studies and regression analysis. 相似文献
2.
Summary Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and sickle cell haemoglobin (Hb S) are red cell genetic abnormalities that occur at a high frequency in several areas of the world including several areas of Saudi Arabia. Genetic and clinical interactions between these two disorders are reported to occur in some populations.In the present investigations, samples from affected individuals were studied for the prevalence of G-6-PD deficiency and Hb S genes. The results of haematological parameters and common clinical findings in the Hb S homozygotes with and without G-6-PD deficiency are presented and the possibility that the two conditions interact beneficially is discussed. 相似文献
3.
Seventy cases of sickle-cell disease were identified in the London Borough of Brent from records dating back to 1962. All but three were still alive and, with one exception, were recalled for confirmation of the diagnosis and to provide personal and family histories. The group consisted of 22 individuals with homozygous sickle-cell anaemia (Hb SS), 12 with sickle-cell/beta-thalassaemia double heterozygosity, 34 with sickle-cell/haemoglobin C disease (Hb SC), and two with the combination of haemoglobin S and hereditary persistence of fetal haemoglobin. They were predominantly of West Indian origin, more than half had been born in Britain, and most were aged under 25. The records for 304 patient admissions between 1962 and 1979 were analysed. There were 199 sickle-cell-disease-related admissions, 61 unrelated to sickle-cell disease, and 44 for pregnancy or its complications. Admissions per patient-year averaged less than one, except for children with Hb SS under the age of 5 years, who were admitted more frequently. The commonest reasons for admission were painful crises (74% of all admissions) and the "chest syndrome" (21%). There were four pneumococcal infections, all in children with Hb SS under the age of 8 years; all recovered. Three patients, aged 10, 15, and 50 years, died. The two children with Hb SS died in their sleep without gross evidence of sickling at necropsy. Multiple brain infarcts were found at necropsy in the 50-year-old woman with Hb SC who, having survived nine uneventful pregnancies, succumbed to an infection after cryosurgery to the cervix. Obstetric records were available for 18 term pregnancies in 11 women. Three antenatal sickling crises and three postpartum thromboembolic complications were encountered. There were no maternal or perinatal deaths. Fifteen asymptomatic individuals with sickle-cell disease were diagnosed as a result of routine screening procedures. There are likely to be many such individuals currently undiagnosed in the community. They urgently need identification because of their increased risks from pregnancy, surgery, and infection. 相似文献
4.
The incidence and the clinical course of patients suffering from sickle-cell syndrome (Hb SS; Hb SC; Hb S thal) in England and Wales are not known. In 1979 an ad hoc committee was formed to investigate these problems. Initially, a questionnaire was sent to 227 haematologists in England and Wales to determine the number of cases in these countries. The replies have indicated that 1367 cases were seen in 1978 and 1979. Probably this may represent only half the total number of cases. From this survey it has been possible to draw up a composite map showing the location of patients, which has provided a basis to determine the clinical course of the disease, and for further studies into the complications and management of sickle-cell disease in England and Wales. From a second questionnaire preliminary data about the general management and mortality in England and Wales have been recorded. 相似文献
5.
Background
Anemia is considered the most common systemic complication of inflammatory bowel disease (IBD). We aimed to provide all available evidence regarding the safety and efficacy of therapy existing today to correct anemia in IBD.Methods
Systematic review and meta-analysis of randomized controlled trials that compared any treatment for anemia in patients with IBD. We searched electronic databases, conference proceedings and clinical trials registries. Two reviewers independently extracted data from included trials. The primary outcome was the effect of treatment for anemia in IBD on the hemoglobin (Hb) response, defined as rate of patients who achieved an increase of 2 g/dl in Hb concentration at the end of the follow-up. Secondary outcomes included disease severity scores, iron indices, Hb levels, inflammatory markers, adverse effects, and mortality. Dichotomous data were analysed by calculating the relative risk (RR) for each trial with the uncertainty in each result being expressed using 95% confidence intervals (CI). A fixed effect model was used, except in the event of significant heterogeneity between the trials (P<0.10, I2>40%), in which we used a random effects model.Results
Nine trials fulfilled the inclusion criteria, to a total of 973 patients. We were able to perform meta-analysis for intravenous (IV) versus oral iron and for ESAs versus placebo. IV iron was associated with a higher rate of achieving Hb response in comparison to oral iron; RR 1.25 (95% CI 1.04–1.51, I2 = 2%, 4 trials), CRP levels and disease activity indexes were not significantly affected by IV iron. IV iron was associated with a decrease in adverse events that required discontinuation of intervention and without an increase in serious adverse.Discussion
Treatment for anemia in IBD should include IV iron and not oral iron replacement, due to improved Hb response, no added toxicity and no negative effect on disease activity. 相似文献6.
This paper reports the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the male and female population of A1-Ula in the northwestern province of Saudi Arabia. The frequency of G6PD deficiency in the male population was 0.098 and in the females it was 0.028. This frequency is significantly lower than those reported for other malaria endemic regions in Arabia. The population was further subgrouped on the basis of their haemoglobin phenotypes and the highest frequency of G6PD deficiency was obtained in male Hb S heterozygotes followed by the male Hb S homozygotes. Phenotyping of G6PD revealed the presence of G6PD-Mediterranean, G6PDA+, G6PDA- and G6PD Mediterranean-like, and the frequency of these variants in Al-Ula was different from those reported in other regions of Saudi Arabia. 相似文献
7.
Nobuyuki Matsumoto Hiroki Ikeda Ryuta Shigefuku Nobuhiro Hattori Tsunamasa Watanabe Kotaro Matsunaga Tetsuya Hiraishi Tomohiro Tamura Yohei Noguchi Yasunobu Fukuda Toshiya Ishii Chiaki Okuse Akira Sato Michihiro Suzuki Fumio Itoh 《PloS one》2016,11(3)
Background
Decreased hemoglobin (Hb) level has been supposed to be a relatively rare side effect of a combination therapy against hepatitis C virus that consists of the NS5A inhibitor daclatasvir (DCV) and the NS3/4A protease inhibitor asunaprevir (ASV).Methods
The study was conducted in 75 patients with genotype 1b chronic hepatitis C virus infection who had started combination therapy with DCV and ASV at St. Marianna University School of Medicine Hospital between September 2014 and December 2014.Results
Among the patients examined, decreased Hb level by ≥1.5 g/dL from the values at treatment initiation was observed in 11 individuals. This was accompanied by decreased mean corpuscular volume, and iron and ferritin levels.Conclusions
These findings suggest that the mechanism of the phenomenon is caused by iron deficiency. The underlying mechanism and clinical impacts will need to be further examined. 相似文献8.
Hoff C Thorneycroft I Wilson F Williams-Murphy M 《Human biology; an international record of research》2001,73(4):583-586
A study of reproductive outcome in Mobile, AL was conducted among a large maternal cohort with sickle-cell disease (Hb SS), sickle-cell trait (Hb AS), and no hemoglobinopathies (Hb AA). It was found that mean gravidity and live births among Hb AS women were significantly higher than among Hb AA women. These findings were surprising since it is generally held that once malarial pressure is alleviated, any reproductive advantage that might be conferred by Hb AS would disappear and fertility levels would reach levels similar to or slightly less than that of Hb AA women. A search of the literature was subsequently conducted and a large cohort study of an African-derived population was found in the United Kingdom. Results from this study also showed that parity was significantly higher among Hb AS women compared to Hb AA women. If survivorship is similar among Hb AS and Hb SS women, findings from these two studies raise doubts whether directional selection is occurring against the Rb S allele in nonmalarial environments. Balancing selection may still be occurring. 相似文献
9.
Blood specimens were obtained from 281 inhabitants of an Eti-Turk village with a population of about 500. Starch gel (pH 8.6) and agar gel (pH 6.45) electrophoresis were performed in 279 of the specimens. Hb S was present in 105 partially interrelated persons (37.36%), three of whom had sickle-cell anaemia. Hb E was detected in 5 persons (1.79%), one of whom was a double heterozygote for Hb S and Hb E. One Hb S+alpha-thalassaemia and 7 Hb S with elevated Hb A'2 combinations were found. The beta-thalassaemia gene prevalence was 0.0377. Hb A2 was found in 4 persons (1.42%), and Hb F was slightly increased in 37 (22.3%) persons with a normal haemoglobin picture. Erythrocyte G-6-PD deficiency was 10% among males. 相似文献
10.
Wieland Voigt Karin Jordan Christoph Sippel Mroawan Amoury Hans-Joachim Schmoll Hans H Wolf 《Journal of medical case reports》2008,2(1):96
Introduction
Platelet counts exceeding 1.000 × 103/μl are usually considered secondary to another cause, particularly to chronic myeloproliferative disease (CMPD). Reactive thrombocytosis due to iron deficiency rarely exceeds platelet counts of 700 × 103/μl.Case presentation
Here we report the case of a young woman presenting with clinical signs of severe anemia. Laboratory findings confirmed an iron-deficiency anemia associated with severe thrombocytosis of 1703 × 103/μl. Macroscopic gastrointestinal and genitourinary tract bleeding was excluded. The excessive elevation of platelets, slightly elevated lactate dehydrogenase and slightly elevated leukocytes along with the absence of other inflammation parameters raised the suspicion of an underlying hematological disease. However, bone marrow evaluation could not prove the suspected diagnosis of a CMPD, especially essential thrombocythemia (ET). In the further clinical course the platelet count returned to normal after raising the hemoglobin to a level close to normal range with erythrocyte transfusion, and normalization of serum iron and decline of erythropoietin. Finally, following small bowel biopsy, despite the absence of typical clinical signs, celiac disease was diagnosed. After discharge from hospital the patient was commenced on a gluten-free diet and her hemoglobin almost completely normalized in the further follow-up period.Conclusion
This case illustrates the rare constellation of an extreme thrombocytosis most likely secondary to iron deficiency due to celiac disease. This represents, to the best of the authors' knowledge, the highest reported platelet count coincident with iron deficiency. A potential mechanism for the association of iron-deficiency anemia and thrombocytosis is discussed. Even in the presence of 'atypically' high platelets one should consider the possibility of reactive thrombocytosis. Extreme thrombocytosis could emerge in the case of iron deficiency secondary to celiac disease.11.
Viana-Baracioli LM Tukamoto Junior NC Ricci Junior O Mattos LC Ângulo IL Bonini-Domingos CR 《Genetics and molecular research : GMR》2011,10(4):3446-3454
It is well documented that Hb S and iron affect blood cells, and trigger oxidative processes and generation of free radicals with potential for lipid peroxidation. We evaluated the frequency of polymorphisms in the HFE gene in Hb AS blood donors and how these polymorphisms influenced lipid peroxidation and antioxidant capacity. Blood samples were collected from 211 Hb AS blood donors, 119 Hb AA blood donors as a control group, and 28 sickle cell disease patients (Hb SS). The H63D allele was found at a frequency of 10.5% in the Hb AS samples, and the C282Y allele frequency was 0.7%. In the control group, the frequencies of the H63D and C282Y alleles were 13.4 and 2.1%, respectively. In the sickle-cell disease patients, the H63D and the C282Y allele frequencies were 10.7 and 3.5%, respectively. The frequencies of the C282Y and H63D polymorphisms in Hb AS blood donors are similar to those reported for the Brazilian population. Serum malondialdehyde values, indicative of lipid peroxidation, were highest in sickle cell patients, independent of the polymorphisms in the HFE gene, with significant differences, showing the influence of Hb S allele in the levels of lipid peroxidation. However, the trolox equivalent antioxidant capacity average levels, indicative of the antioxidant capacity, were reduced with significant differences, indicating that in spite of a lipid peroxidation raise, this is not followed by the increased of the antioxidant capacity, leading to oxidative stress. 相似文献
12.
Eliezer A. Rachmilewitz Hanna Tamari Fanny Liff Yoshihiro Ueda R. L. Nagel 《Human genetics》1985,70(2):119-125
Summary We have studied 105 individuals in the village of Jasser El Zarka in the Northern Coast of Israel of whom 59% had at least one abnormal hemoglobin. Of the individuals studied 41% were AA, 13.3% AS, 28.6% AOArab, 10.5% SOArab, 0.9% SS, 38% Arab-+ Thal, and 1.9% Thal trait. The SOArab double heterozygotes were characterized by a normal mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC), and an increase of Hb F (11.7±4.3%) and 2,3-diphosphoglycerate levels (27.8 m/g Hb). The increase of Hb F is higher than the one seen among OArabs of other ethnic backgrounds. Their clinical course was moderately severe and osteoporosis was quite frequent. The interactions of Hb OArab and Hb S were studied in vitro and it was confirmed the Hb OArab lowers the minimal gelling concentration of mixtures with Hb S (as compared to mixtures of Hb S and Hb A), but that this effect is ionic-strength dependent. Our data are in conflict with previous claims that Hb OArab mixtures with Hb S polymerized almost as much as pure S. Oxygen association curves show a significant displacement of the p50 to the right, but the effect of oxygen dissociation is less apparent. The displacement was not nearly as significant as with SS cells, confirming our gelation data. Blood group determinations establish that these Arab populations had black African admixture.The Hb OArab/+ Thal double heterozygotes exhibit moderate anemia (10.3g% of Hb) and the percentage of Hb A was 17.2±1.8%. The fetal Hb was 5.4±2.1% and the 2,3-diphosphoglycerate level in two cases was 17.4 mol/g Hb. The only case of a homozygote SS had moderate anemia (10.3 g Hb%), 25.7% of Hb F, and a very benign course. 相似文献
13.
Helianthus annuus L. responds to iron deficiency by forming a thickened cortex and abundant root hairs in a zone near the root apex that corresponds to the primary developmental stage. Cytological investigations revealed that within 24 to 48 h of iron deficiency most of the peripheral cells differentiate into transfer cells. The wall labyrinth is always situated on the peripheral walls that face the external medium. The cytoplasm of these cells is characterized by numerous mitochondria, extensive rough endoplasmic reticulum, and large leucoplasts containing protein bodies. These observations are discussed in relation to the fact that Helianthus, as an iron efficient plant, responds physiologically to iron deficiency by extrusion of H+, production of reducing substances, and a steep increase in the uptake efficiency of Fe. 相似文献
14.
Mohsen A. F. El-Hazmi Arjumand S. Warsy Mohamed H. N. Addar Zeinab Babae 《Molecular and cellular biochemistry》1994,135(2):181-186
Fetal haemoglobin (HbF) level shows significant variations in health and disease states. In this study we investigated Hb F level in 75 cord bloods, 1266 healthy individuals, 1582 Hb S heterozygotes, 464 sickle cell anaemia, 93 Hb S/2-thalassemia and 65 -thalassemia major patients. The age range of the study groups varied from newborn to over 60 years of age. Hb F level was measured by an alkali denaturation procedure and by radial immunodiffusion. The ratio of the level of G-globin chains to the level of A-globin chains (G/A) was determined in the patients group by high performance liquid chromatography. The Hb F level was significantly higher in the sickle cell anaemia and -thalassemia major patients compared to the Hb S heterozygotes and the normal individuals. Within each group Hb F level was higher in the female population compared to the age-matched male groups. This difference was statistically significant (P<0.05) in the sickle cell disease patients and -thalassemia major patients but not in the normal individuals. After the age of 30 years, the difference in the value of Hb F in the male and female population become more apparent (P<0.05) in the sickle cell disease and -thalassaemia major patients. No statistically significant sex differences were found in the G/Aratio in the patient groups, and the range of G/Aratio in the patients groups were similar to those in the control group.The results showed that age, sex and genetic disorders of haemoglobin are factors that affect Hb F level and indicate the possible involvement of an X-linked factor in control of Hb F production. 相似文献
15.
Inka Gallitz Niklas Lofruthe Lisa Traeger Nicole Bäumer Verena Hoerr Cornelius Faber Tanja Kuhlmann Carsten Müller-Tidow Andrea U. Steinbicker 《BMC physiology》2018,18(1):3
Background
Inflammatory stimuli induce the hepatic iron regulatory hormone hepcidin, which contributes to anaemia of inflammation (AI). Hepcidin expression is regulated by the bone morphogenetic protein (BMP) and the interleukin-6 (IL-6) signalling pathways. Prior results indicate that the BMP type I receptor ALK3 is mainly involved in the acute inflammatory hepcidin induction four and 72 h after IL-6 administration. In this study, the role of ALK3 in a chronic model of inflammation was investigated. The intact, heat-killed bacterium Brucella abortus (BA) was used to analyse its effect on the development of inflammation and hypoferremia in mice with hepatocyte-specific Alk3-deficiency (Alk3fl/fl; Alb-Cre) compared to control (Alk3fl/fl) mice.Results
An iron restricted diet prevented development of the iron overload phenotype in mice with hepatocyte-specific Alk3 deficiency. Regular diet leads to iron overload and increased haemoglobin levels in these mice, which protects from the development of AI per se. Fourteen days after BA injection Alk3fl/fl; Alb-Cre mice presented milder anaemia (Hb 16.7 g/dl to 11.6 g/dl) compared to Alk3fl/fl control mice (Hb 14.9 g/dl to 8.6 g/dl). BA injection led to an intact inflammatory response in all groups of mice. In Alk3fl/fl; Alb-Cre mice, SMAD1/5/8 phosphorylation was reduced after BA as well as after infection with Staphylococcus aureus. The reduction of the SMAD1/5/8 signalling pathway due to hepatocyte-specific Alk3 deficiency partly suppressed the induction of STAT3 signalling.Conclusion
The results reveal in vivo, that 1) hepatocyte-specific Alk3 deficiency partly protects from AI, 2) the development of hypoferremia is partly dependent on ALK3, and 3) the ALK3/BMP/hepcidin axis may serve as a possible therapeutic target to attenuate AI.16.
Jing Chen‐Roetling Sheng‐Kai Ma Yang Cao Aishwarya Shah Raymond F. Regan 《Journal of neurochemistry》2018,145(6):464-473
17.
Cristy L. Gelling Ian W. Dawes David H. Perlmutter Edward A. Fisher Jeffrey L. Brodsky 《Genetics》2012,192(3):889-903
Up to 1 in 3000 individuals in the United States have α-1 antitrypsin deficiency, and the most common cause of this disease is homozygosity for the antitrypsin-Z variant (ATZ). ATZ is inefficiently secreted, resulting in protein deficiency in the lungs and toxic polymer accumulation in the liver. However, only a subset of patients suffer from liver disease, suggesting that genetic factors predispose individuals to liver disease. To identify candidate factors, we developed a yeast ATZ expression system that recapitulates key features of the disease-causing protein. We then adapted this system to screen the yeast deletion mutant collection to identify conserved genes that affect ATZ secretion and thus may modify the risk for developing liver disease. The results of the screen and associated assays indicate that ATZ is degraded in the vacuole after being routed from the Golgi. In fact, one of the strongest hits from our screen was Vps10, which can serve as a receptor for the delivery of aberrant proteins to the vacuole. Because genome-wide association studies implicate the human Vps10 homolog, sortilin, in cardiovascular disease, and because hepatic cell lines that stably express wild-type or mutant sortilin were recently established, we examined whether ATZ levels and secretion are affected by sortilin. As hypothesized, sortilin function impacts the levels of secreted ATZ in mammalian cells. This study represents the first genome-wide screen for factors that modulate ATZ secretion and has led to the identification of a gene that may modify disease severity or presentation in individuals with ATZ-associated liver disease. 相似文献
18.
Andriy O Samokhin Jacques Yves Gauthier M David Percival Dieter Br?mme 《Respiratory research》2011,12(1):13
Background
Remodeling of lung tissues during the process of granuloma formation requires significant restructuring of the extra-cellular matrix and cathepsins K, L and S are among the strongest extra-cellular matrix degrading enzymes. Cathepsin K is highly expressed in various pathological granulomatous infiltrates and all three enzymes in their active form are detected in bronchoalveolar lavage fluids from patients with sarcoidosis. Granulomatous inflammation is driven by T-cell response and cathepsins S and L are actively involved in the regulation of antigen presentation and T-cell selection. Here, we show that the disruption of the activities of cathepsins K, L, or S affects the development of lung granulomas in a mouse model of sarcoidosis.Methods
Apolipoprotein E-deficient mice lacking cathepsin K or L were fed Paigen diet for 16 weeks and lungs were analyzed and compared with their cathepsin-expressing littermates. The role of cathepsin S in the development of granulomas was evaluated using mice treated for 8 weeks with a potent and selective cathepsin S inhibitor.Results
When compared to wild-type litters, more cathepsin K-deficient mice had lung granulomas, but individually affected mice developed smaller granulomas that were present in lower numbers. The absence of cathepsin K increased the number of multinucleated giant cells and the collagen content in granulomas. Cathepsin L deficiency resulted in decreased size and number of lung granulomas. Apoe-/- mice treated with a selective cathepsin S inhibitor did not develop lung granulomas and only individual epithelioid cells were observed.Conclusions
Cathepsin K deficiency affected mostly the occurrence and composition of lung granulomas, whereas cathepsin L deficiency significantly reduced their number and cathepsin S inhibition prevented the formation of granulomas. 相似文献19.
Lucile Mercadel Marie Metzger Jean Philippe Haymann Eric Thervet Jean-Jacques Boffa Martin Flamant Fran?ois Vrtovsnik Pascal Houillier Marc Froissart Bénédicte Stengel the NephroTest Study Group 《PloS one》2014,9(6)
The metabolism of hepcidin is profoundly modified in chronic kidney disease (CKD). We investigated its relation to iron disorders, inflammation and hemoglobin (Hb) level in 199 non-dialyzed, non-transplanted patients with CKD stages 1–5. All had their glomerular filtration rate measured by 51Cr-EDTA renal clearance (mGFR), as well as measurements of iron markers including hepcidin and of erythropoietin (EPO). Hepcidin varied from 0.2 to 193 ng/mL. The median increased from 23.3 ng/mL [8.8–28.7] to 36.1 ng/mL [14.1–92.3] when mGFR decreased from ≥60 to <15 mL/min/1.73 m2 (p = 0.02). Patients with absolute iron deficiency (transferrin saturation (TSAT) <20% and ferritin <40 ng/mL) had the lowest hepcidin levels (5.0 ng/mL [0.7–11.7]), and those with a normal iron profile (TSAT ≥20% and ferritin ≥40), the highest (34.5 ng/mL [23.7–51.6]). In multivariate analysis, absolute iron deficiency was associated with lower hepcidin values, and inflammation combined with a normal or functional iron profile with higher values, independent of other determinants of hepcidin concentration, including EPO, mGFR, and albuminemia. The hepcidin level, although it rose overall when mGFR declined, collapsed in patients with absolute iron deficiency. There was a significant interaction with iron status in the association between Hb and hepcidin. Except in absolute iron deficiency, hepcidin’s negative association with Hb level indicates that it is not down-regulated in CKD anemia. 相似文献
20.