Результаты поиска

Recent advances in understanding clonal haematopoiesis in aplastic anaemia.

Acquired aplastic anaemia (AA) is an immune-mediated bone marrow failure disorder inextricably linked to clonal haematopoiesis. The majority of AA patients have somatic mutations and/or structural chromosomal abnormalities detected as early as at diagnosis. In contrast to other conditions linked to clonal haematopoiesis, the clonal signature of AA reflects its immune pathophysiology. The most common alterations are clonal expansions of cells lacking glycophosphotidylinositol-anchored proteins, loss of human leucocyte antigen alleles, and mutations in BCOR/BCORL1, ASXL1 and DNMT3A. Here, we pre

Frosted Branch Angiitis in Pediatric Dyskeratosis Congenita: A Case Report.

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome, usually presented with abnormal skin pigmentation, nail dystrophy, and oral leukoplakia. The main cause of mortality in DC is immunodeficiency and vital infection. DC involves multisystem, but retinal involvements are rare.Herein, we report an unusual case of pediatric DC suffering from frosted branch angiitis (FBA) after recovery of mycoplasma pneumonia. Cytomegalovirus infection and cytokine changes were found relevant to the onset of FBA. Despite corticosteroids, antiviral medication, and hematopoietic stem cell trans

Single nucleotide polymorphism array analysis of bone marrow failure patients reveals characteristic patterns of genetic changes.

The bone marrow failure syndromes (BMFS) are a heterogeneous group of rare blood disorders characterized by inadequate haematopoiesis, clonal evolution, and increased risk of leukaemia. Single nucleotide polymorphism arrays (SNP-A) have been proposed as a tool for surveillance of clonal evolution in BMFS. To better understand the natural history of BMFS and to assess the clinical utility of SNP-A in these disorders, we analysed 124 SNP-A from a comprehensively characterized cohort of 91 patients at our BMFS centre. SNP-A were correlated with medical histories, haematopathology, cytogenetic and

Arsine toxicity aboard the Asiafreighter.

Eight sailors on board the Asiafreighter were exposed to arsine that had escaped from a cylinder in the cargo hold. Four suffered severe toxicity and within a few hours had developed fever, weakness, nausea, vomiting, diarrhoea, abdominal pain, and haemoglobinuria. These patients had pronounced intravascular haemolysis, which in one patient was complete. This patient was also stuporose and anoxic, a condition attributed to failure of oxygen transport and sludging of red cell debris in the cerebral and pulmonary circulations, but he regained a normal level of consciousness after exchange transf

The impact of category, cytopathology and cytogenetics on development and progression of clonal and malignant myeloid transformation in inherited bone marrow failure syndromes.

Inherited bone marrow failure syndromes are a group of rare, heterogeneous genetic disorders with a risk of clonal and malignant myeloid transformation including clonal marrow cytogenetic abnormalities, myelodysplastic syndrome and acute myeloid leukemia. The clinical characteristics, risk classification, prognostic factors and outcome of clonal and malignant myeloid transformation associated with inherited bone marrow failure syndromes are largely unknown. The aims of this study were to determine the impact of category, cytopathology and cytogenetics, the three components of the "Category Cyt

Differential diagnosis of Hb EE and Hb E-beta(0)-thalassemia by protein and DNA analyses.

DNA analysis was used to confirm the Hb EE genotype and to differentiate from the possible genotype of Hb E-beta(0)-thalassemia in two Malay patients. The first patient was a 13-year-old Malay girl, whose parents were available for family studies. The second patient was a 69-year-old Malay woman with no living family members. The presence of Hb E in both propositi was confirmed by: (1) its characteristic electrophoretic mobilities on alkaline/acid gels; (2) its chromatographic properties on anion/cation exchangers, and (3) its mildly insoluble properties. However, differential diagnosis of Hb

Modulation of splicing catalysis for therapeutic targeting of leukemia with mutations in genes encoding spliceosomal proteins.

Mutations in genes encoding splicing factors (which we refer to as spliceosomal genes) are commonly found in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). These mutations recurrently affect specific amino acid residues, leading to perturbed normal splice site and exon recognition. Spliceosomal gene mutations are always heterozygous and rarely occur together with one another, suggesting that cells may tolerate only a partial deviation from normal splicing activity. To test this hypothesis, we engineered mice to express a mutated allele of serine/arginine-rich s

Type 1 interferons suppress accelerated osteoclastogenesis and prevent loss of bone mass during systemic inflammatory responses to Pneumocystis lung infection.

HIV infection causes loss of CD4(+) T cells and type 1 interferon (IFN)-producing and IFN-responsive dendritic cells, resulting in immunodeficiencies and susceptibility to opportunistic infections, such as Pneumocystis. Osteoporosis and bone marrow failure are additional unexplained complications in HIV-positive patients and patients with AIDS, respectively. We recently demonstrated that mice that lack lymphocytes and IFN a/b receptor (IFrag(-/-)) develop bone marrow failure after Pneumocystis lung infection, whereas lymphocyte-deficient, IFN α/β receptor-competent mice (RAG(-/-)) had normal h

Histologic Features of Intestinal Thrombotic Microangiopathy in Pediatric and Young Adult Patients after Hematopoietic Stem Cell Transplantation.

High-risk transplantation-associated thrombotic microangiopathy (TMA) can present with multisystem involvement and is associated with a poor outcome after hematopoietic stem cell transplantation (HSCT), with < 20% 1-year survival. TMA may involve the intestinal vasculature and can present with bleeding and ischemic colitis. There are no established pathologic criteria for the diagnosis of intestinal TMA (iTMA). The goal of our study was to identify histologic features of iTMA and describe associated clinical features. We evaluated endoscopic samples from 50 consecutive HSCT patients for 8 hist

A randomised controlled trial of cognitive behaviour therapy and motivational interviewing for people with Type 1 diabetes mellitus with persistent sub-optimal glycaemic control: a Diabetes and Psychological Therapies (ADaPT) study.

OBJECTIVES: To determine whether (i) motivational enhancement therapy (MET) + cognitive behaviour therapy (CBT) compared with usual care, (ii) MET compared with usual care, (iii) or MET + CBT compared with MET was more effective in improving glycaemic control when delivered by general nurses with additional training in these techniques. DESIGN: A three-arm parallel randomised controlled trial as the gold standard design to test the effectiveness of psychological treatments. SETTING: The recruiting centres were diabetes clinics in seven acute trusts in south-east London and Greater Manchester

Biological and molecular characterization of PNH-like lymphocytes emerging after Campath-1H therapy.

Campath-1H, an anti-CD52 monoclonal antibody, is therapeutically active in lymphoproliferative and autoimmune diseases. After Campath-1H therapy, lymphocytes with a paroxysmal nocturnal haemoglobinuria (PNH) phenotype have been reported to emerge. We characterized a PNH-like lymphocyte population emerging after Campath-1H therapy, in a patient with fludarabine refractory B-cell chronic lymphocytic leukaemia (B-CLL). We demonstrated a reduction in PIG-A mRNA levels compared with controls, and of all cytokines tested [interleukin (IL)-4, IL-13, IL-2, interferon(IFN)-gamma, IL-6, IL-10, and tumou

Mechanisms by which the surface expression of the glycosyl-phosphatidylinositol-anchored complement regulatory proteins decay-accelerating factor (CD55) and CD59 is lost in human leukaemia cell lines.

We have investigated the mechanisms of defects in the glycosyl-phosphatidylinositol (GPI)-anchored complement regulatory proteins delay-accelerating factor (DAF) and/or CD59 in a panel of human leukaemia cell lines that lack surface expression of these proteins: U937 (DAF+/CD59-), CEM (DAF-/CD59+), TALL (DAF-/CD59-) and a substrain of Ramos [Ramos(-)] (DAF-/CD59-). Northern blotting and reverse transcription-PCR revealed that the main cause of the DAF and/or CD59 deficiency is the failure of mRNA expression in most of the cell lines, except in Ramos(-) in which sufficient mRNA for DAF and CD59

Disease Activity After Switching From Eculizumab to Ravulizumab in Patients With Paroxysmal Nocturnal Haemoglobinuria: Real World Data From Denmark and Finland.

INTRODUCTION: Ravulizumab replaced eculizumab as the preferred complement inhibitor for Paroxysmal Nocturnal Haemoglobinuria (PNH) in Denmark and Finland after 2020. Data on real-world disease activity after switching are limited. METHODS: We conducted a case series of 20 PNH patients who transitioned from eculizumab to ravulizumab, assessing transfusion needs and breakthrough haemolysis episodes (BTH). RESULTS: In 19 of 20 patients, transfusions and BTH were stable or reduced after switching. Particularly, patients with high transfusion or BTH burden had a marked reduction in these paramete

Совпадение в полном тексте источника
… BTH signs monitored included hemoglobinuria, fatigue, abdominal pain, dyspnea, or hemoglobin drop <6.3 g/dL. … Brodsky R A., “Paroxysmal Nocturnal Hemoglobinuria,” Blood 124, no. 18 (2014): 2804–2811. 2. Hillmen P., Lewis S. M., Bessler M., Luzzatto L., and Dacie J. V., “Natural History of Paroxysmal Nocturnal Hemoglobinuria,” New England Journal of Medicine 333, no. 19 (1995): 1253–1258. 3. Kelly R. …

The burden of illness of patients with paroxysmal nocturnal haemoglobinuria receiving C5 inhibitors in France, Germany and the United Kingdom: Patient-reported insights on symptoms and quality of life.

OBJECTIVES: To assess the clinical, humanistic and economic burden of paroxysmal nocturnal haemoglobinuria (PNH) among C5 inhibitor (C5i)-treated patients with PNH. METHODS: This was a web-based, cross-sectional survey (01FEB2021-31MAR2021) of adults with PNH treated with eculizumab (France, Germany, United Kingdom) or ravulizumab (Germany). Self-reported outcomes included: patient characteristics; patient-reported symptoms; and standardised patient-reported outcomes (e.g. Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue, European Organization for Research and Treatment of Can

Совпадение в полном тексте источника
… Anti‐complement treatment for paroxysmal nocturnal hemoglobinuria: time for proximal complement inhibition? A position paper from the SAAWP of the EBMT. Front Immunol. 2019;10:1157. doi: 10.3389/fimmu.2019.01157 9. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. … COVID‐19 vaccines induce severe hemolysis in paroxysmal nocturnal hemoglobinuria. Blood. 2021;137(26):3670‐3673. doi: 10.1182/blood.2021011548 49. Hines A, Hakim N, Barrientos J. COVID‐19 infection presenting as paroxysmal nocturnal hemoglobinuria. …

Clinical Utility of Computed Tomography and Magnetic Resonance Imaging for Diagnosis of Posterior Reversible Encephalopathy Syndrome after Stem Cell Transplantation in Children and Adolescents.

Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome characterized by vision changes, altered mental status, and seizures, typically caused by an acute rise in blood pressure. PRES has been reported after hematopoietic stem cell transplantation (HSCT) in association with hypertension from calcineurin inhibitors and corticosteroids. The imaging evaluation of PRES after HSCT in children and young adults has not been well described. We performed a retrospective review of all HSCT recipients presenting to the intensive care unit with new neurologic symptoms. A neuroradiologis

Kit-Shp2-Kit signaling acts to maintain a functional hematopoietic stem and progenitor cell pool.

The stem cell factor (SCF)/Kit system has served as a classic model in deciphering molecular signaling events in the hematopoietic compartment, and Kit expression is a most critical marker for hematopoietic stem cells (HSCs) and progenitors. However, it remains to be elucidated how Kit expression is regulated in HSCs. Herein we report that a cytoplasmic tyrosine phosphatase Shp2, acting downstream of Kit and other RTKs, promotes Kit gene expression, constituting a Kit-Shp2-Kit signaling axis. Inducible ablation of PTPN11/Shp2 resulted in severe cytopenia in BM, spleen, and peripheral blood in