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Sub-cellular Biochemistry 2020This chapter reviews how allosteric (heterotrophic) effectors and natural mutations impact hemoglobin (Hb) primary physiological function of oxygen binding and... (Review)
Review
This chapter reviews how allosteric (heterotrophic) effectors and natural mutations impact hemoglobin (Hb) primary physiological function of oxygen binding and transport. First, an introduction about the structure of Hb is provided, including the ensemble of tense and relaxed Hb states and the dynamic equilibrium of Hb multistate. This is followed by a brief review of Hb variants with altered Hb structure and oxygen binding properties. Finally, a review of different endogenous and exogenous allosteric effectors of Hb is presented with particular emphasis on the atomic interactions of synthetic ligands with altered allosteric function of Hb that could potentially be harnessed for the treatment of diseases.
Topics: Allosteric Regulation; Hematologic Diseases; Hemoglobins; Humans; Ligands; Oxygen
PubMed: 32189307
DOI: 10.1007/978-3-030-41769-7_14 -
American Journal of Physiology. Cell... Jan 2022SARS-CoV-2 has rapidly spread across the globe and infected hundreds of millions of people worldwide. As our experience with this virus continues to grow, our... (Review)
Review
SARS-CoV-2 has rapidly spread across the globe and infected hundreds of millions of people worldwide. As our experience with this virus continues to grow, our understanding of both short-term and long-term complications of infection with SARS-CoV-2 continues to grow as well. Just as there is heterogeneity in the acute infectious phase, there is heterogeneity in the long-term complications seen following COVID-19 illness. The purpose of this review article is to present the current literature with regards to the epidemiology, pathophysiology, and proposed management algorithms for the various long-term sequelae that have been observed in each organ system following infection with SARS-CoV-2. We will also consider future directions, with regards to newer variants of the virus and their potential impact on the long-term complications observed.
Topics: Algorithms; COVID-19; Cardiovascular Diseases; Central Nervous System Diseases; Disease Progression; Hematologic Diseases; Humans; SARS-CoV-2; Post-Acute COVID-19 Syndrome
PubMed: 34817268
DOI: 10.1152/ajpcell.00375.2021 -
Acta Haematologica 2021Rheumatic diseases have many hematological manifestations. Blood dyscrasias and other hematological abnormalities are sometimes the first sign of rheumatic disease. In... (Review)
Review
BACKGROUND
Rheumatic diseases have many hematological manifestations. Blood dyscrasias and other hematological abnormalities are sometimes the first sign of rheumatic disease. In addition, novel antirheumatic biological agents may cause cytopenias.
SUMMARY
The aim of this review was to discuss cytopenias caused by systemic lupus erythematosus and antirheumatic drugs, Felty's syndrome in rheumatoid arthritis, and autoimmune hemolytic anemia, thrombosis, and thrombotic microangiopathies related to rheumatological conditions such as catastrophic antiphospholipid syndrome and scleroderma renal crisis. Key Message: The differential diagnosis of various hematological disorders should include rheumatic autoimmune diseases among other causes of blood cell and hemostasis abnormalities. It is crucial that hematologists be aware of these presentations so that they are diagnosed and treated in a timely manner.
Topics: Anemia, Hemolytic; Antirheumatic Agents; Felty Syndrome; Glucocorticoids; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Leukopenia; Lupus Erythematosus, Systemic; Protein Kinase Inhibitors; Rheumatic Diseases
PubMed: 33221805
DOI: 10.1159/000511759 -
Discovery Medicine 2019Pernicious anemia (PA), the commonest cause of cobalamin deficiency (CD) in the world, is an autoimmune disease of multifactorial origin and is characterized by chronic... (Review)
Review
Pernicious anemia (PA), the commonest cause of cobalamin deficiency (CD) in the world, is an autoimmune disease of multifactorial origin and is characterized by chronic atrophic gastritis (CAG) and defective absorption of cobalamin from the terminal ileum due to interference by the intrinsic factor (IF) antibodies. PA-related CD is a lengthy process, which if untreated, can lead to irreversible hematological and neurological sequelae. Although safe and effective therapy is available and the management of PA is straightforward, the diagnosis of PA can be extremely difficult to obtain due to myriad and diverse clinical presentations, frequently coexisting diseases, and limitations of currently available diagnostic tests. Diagnostic dilemmas may occur when PA patients present with normal or spuriously high serum cobalamin levels, dysplastic features of ring sideroblasts in the bone marrow (BM), hemolysis, and concomitant diseases such as iron deficiency or thalassemia. Herein, the author discusses an overview of diagnostic difficulties, with regards to morphological mimics, coexisting diseases, limitations of currently available tests, and how to diagnose PA in the era of imperfect laboratory tests.
Topics: Anemia, Pernicious; Autoantibodies; Biomarkers; Hematologic Tests; Humans
PubMed: 32053765
DOI: No ID Found -
Genes Mar 2021Kabuki syndrome (KS) is a rare developmental disorder principally comprised of developmental delay, hypotonia and a clearly defined dysmorphism: elongation of the... (Review)
Review
Kabuki syndrome (KS) is a rare developmental disorder principally comprised of developmental delay, hypotonia and a clearly defined dysmorphism: elongation of the structures surrounding the eyes, a shortened and depressed nose, thinning of the upper lip and thickening of the lower lip, large and prominent ears, hypertrichosis and scoliosis. Other characteristics include poor physical growth, cardiac, gastrointestinal and renal anomalies as well as variable behavioral issues, including autistic features. De novo or inherited pathogenic/likely pathogenic variants in the gene are the most common cause of KS and account for up to 75% of patients. Variants in cause up to 5% of cases (X-linked dominant inheritance), while the etiology of about 20% of cases remains unknown. Current KS diagnostic criteria include hypotonia during infancy, developmental delay and/or intellectual disability, typical dysmorphism and confirmed pathogenic/likely pathogenic variant in or . Care for KS patients includes the control of physical and psychomotor development during childhood, rehabilitation and multi-specialist care. This paper reviews the current clinical knowledge, provides molecular and scientific links and sheds light on the treatment of Kabuki syndrome individuals.
Topics: Abnormalities, Multiple; DNA-Binding Proteins; Face; Hematologic Diseases; Histone Demethylases; Humans; Mutation; Neoplasm Proteins; Phenotype; Vestibular Diseases
PubMed: 33805950
DOI: 10.3390/genes12040468 -
Blood Feb 2022Kaposi sarcoma (KS) herpesvirus (KSHV), also known as human herpesvirus 8, is the causal agent of KS but is also pathogenetically related to several lymphoproliferative... (Review)
Review
Kaposi sarcoma (KS) herpesvirus (KSHV), also known as human herpesvirus 8, is the causal agent of KS but is also pathogenetically related to several lymphoproliferative disorders, including primary effusion lymphoma (PEL)/extracavitary (EC) PEL, KSHV-associated multicentric Castleman disease (MCD), KSHV+ diffuse large B-cell lymphoma, and germinotropic lymphoproliferative disorder. These different KSHV-associated diseases may co-occur and may have overlapping features. KSHV, similar to Epstein-Barr virus (EBV), is a lymphotropic gammaherpesvirus that is preferentially present in abnormal lymphoid proliferations occurring in immunecompromised individuals. Notably, both KSHV and EBV can infect and transform the same B cell, which is frequently seen in KSHV+ EBV+ PEL/EC-PEL. The mechanisms by which KSHV leads to lymphoproliferative disorders is thought to be related to the expression of a few transforming viral genes that can affect cellular proliferation and survival. There are critical differences between KSHV-MCD and PEL/EC-PEL, the 2 most common KSHV-associated lymphoid proliferations, including viral associations, patterns of viral gene expression, and cellular differentiation stage reflected by the phenotype and genotype of the infected abnormal B cells. Advances in treatment have improved outcomes, but mortality rates remain high. Our deepening understanding of KSHV biology, clinical features of KSHV-associated diseases, and newer clinical interventions should lead to improved and increasingly targeted therapeutic interventions.
Topics: Epstein-Barr Virus Infections; Hematologic Diseases; Herpesvirus 4, Human; Herpesvirus 8, Human; Humans; Lymphoproliferative Disorders; Sarcoma, Kaposi
PubMed: 34479367
DOI: 10.1182/blood.2020005470 -
Blood Dec 2021The BCL6 corepressor (BCOR) is a transcription factor involved in the control of embryogenesis, mesenchymal stem cells function, hematopoiesis, and lymphoid development.... (Review)
Review
The BCL6 corepressor (BCOR) is a transcription factor involved in the control of embryogenesis, mesenchymal stem cells function, hematopoiesis, and lymphoid development. Recurrent somatic clonal mutations of the BCOR gene and its homolog BCORL1 have been detected in several hematologic malignancies and aplastic anemia. They are scattered across the whole gene length and mostly represent frameshifts (deletions, insertions), nonsense, and missence mutations. These disruptive events lead to the loss of full-length BCOR protein and to the lack or low expression of a truncated form of the protein, both consistent with the tumor suppressor role of BCOR.BCOR and BCORL1 mutations are similar to those causing 2 rare X-linked diseases: oculofaciocardiodental (OFCD) and Shukla-Vernon syndromes, respectively. Here, we focus on the structure and function of normal BCOR and BCORL1 in normal hematopoietic and lymphoid tissues and review the frequency and clinical significance of the mutations of these genes in malignant and nonmalignant hematologic diseases. Moreover, we discuss the importance of mouse models to better understand the role of Bcor loss, alone and combined with alterations of other genes (eg, Dnmt3a and Tet2), in promoting hematologic malignancies and in providing a useful platform for the development of new targeted therapies.
Topics: Animals; Gene Expression Regulation, Neoplastic; Hematologic Diseases; Hematologic Neoplasms; Humans; Mutation; Proto-Oncogene Proteins; Repressor Proteins
PubMed: 33945606
DOI: 10.1182/blood.2021010958 -
Medicine Nov 2021β-thalassemia is a hereditary hematological disease caused by over 350 mutations in the β-globin gene (HBB). Identifying the genetic variants affecting fetal... (Review)
Review
β-thalassemia is a hereditary hematological disease caused by over 350 mutations in the β-globin gene (HBB). Identifying the genetic variants affecting fetal hemoglobin (HbF) production combined with the α-globin genotype provides some prediction of disease severity for β-thalassemia. However, the generation of an additive composite genetic risk score predicts prognosis, and guide management requires a larger panel of genetic modifiers yet to be discovered.Presently, using data from prior clinical trials guides the design of further research and academic studies based on gene augmentation, while fundamental insights into globin switching and new technology developments have inspired the investigation of novel gene therapy approaches.Genetic studies have successfully characterized the causal variants and pathways involved in HbF regulation, providing novel therapeutic targets for HbF reactivation. In addition to these HBB mutation-independent strategies involving HbF synthesis de-repression, the expanding genome editing toolkit provides increased accuracy to HBB mutation-specific strategies encompassing adult hemoglobin restoration for personalized treatment of hemoglobinopathies. Allogeneic hematopoietic stem cell transplantation was, until very recently, the curative option available for patients with transfusion-dependent β-thalassemia. Gene therapy currently represents a novel therapeutic promise after many years of extensive preclinical research to optimize gene transfer protocols.We summarize the current state of developments in the molecular genetics of β-thalassemia over the last decade, including the mechanisms associated with ineffective erythropoiesis, which have also provided valid therapeutic targets, some of which have been shown as a proof-of-concept.
Topics: Fetal Hemoglobin; Gene Editing; Hemoglobinopathies; Humans; Molecular Biology; beta-Thalassemia
PubMed: 34766559
DOI: 10.1097/MD.0000000000027522 -
Clinical Chemistry and Laboratory... Nov 2019This review evaluates the role of platelets in bleeding risk among patients with hematological disease and thrombocytopenia. Platelets are pivotal in primary hemostasis,... (Review)
Review
This review evaluates the role of platelets in bleeding risk among patients with hematological disease and thrombocytopenia. Platelets are pivotal in primary hemostasis, and possess non-hemostatic properties involved in angiogenesis, tissue repair, inflammation and metastatis. Also, platelets safeguard vascular integrity in inflamed vessels. Overall, bleeding risk depends on the underlying disease, and patients with cancer and platelet count <6-10 × 109/L have a markedly increased bleeding risk, while the platelet count does not correlate with bleeding risk at higher platelet counts. Other factors might affect platelet properties and thus bleeding risk, for example, drugs, low hematocrit, coagulation system impairments or transfusion of dysfunctional donor platelets. For patients with leukemia and immune thrombocytopenia, reduced platelet activation, platelet aggregation, or thrombopoiesis, reflected by the reduced presence of reticulated platelets, are associated with bleeding phenotype. However, mechanistic insight into the cause of reduced platelet function in different thrombocytopenic conditions is sparse, except for some inherited platelet disorders. Promising tools for platelet function studies in thrombocytopenia are flow cytometry and biomarker studies on platelet constituents. An important message from this current paper is that bleeding risk assessment must be tailored to specific patient populations and cannot be applied broadly to all patients with thrombocytopenia.
Topics: Blood Coagulation; Blood Platelets; Blood Transfusion; Female; Hematologic Diseases; Hemorrhage; Hemostasis; Humans; Leukopenia; Male; Platelet Activation; Platelet Aggregation; Platelet Count; Platelet Function Tests; Risk Factors; Thrombocytopenia
PubMed: 31465290
DOI: 10.1515/cclm-2019-0380 -
Revista Espanola de Quimioterapia :... Sep 2019Catheter-related bloodstream infections (CRBSI) is a common cause of nosocomial infection associated resulting in substantial morbidity, mortality, increased length of... (Review)
Review
Catheter-related bloodstream infections (CRBSI) is a common cause of nosocomial infection associated resulting in substantial morbidity, mortality, increased length of hospital stays and health-care costs. New clinical practice guidelines for the management of adults with CRBSI have been published in 2018 by the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC). This review focuses on updated recommendations for the diagnosis and management of CRBSI in adults. Prevention of CRBSI is excluded. Our aim is to show some of the key aspects concerning the following topics: diagnosis, empirical and targeted therapy.
Topics: Catheter-Related Infections; Critical Care; Cross Infection; Hematologic Diseases; Humans
PubMed: 31475809
DOI: No ID Found