Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma.

Multiple myeloma (MM) is characterized by an uninhibited, clonal growth of plasma cells. While first-degree relatives of patients with MM show an increased risk of MM, the genetic basis of inherited MM susceptibility is incompletely understood. Here we report a genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 (rs56219066T; odds ratio (OR)=1.

Inherited polymorphisms in hyaluronan synthase 1 predict risk of systemic B-cell malignancies but not of breast cancer.

Genetic variations in the hyaluronan synthase 1 gene (HAS1) influence HAS1 aberrant splicing. HAS1 is aberrantly spliced in malignant cells from multiple myeloma (MM) and Waldenstrom macroglobulinemia (WM), but not in their counterparts from healthy donors. The presence of aberrant HAS1 splice variants predicts for poor survival in multiple myeloma (MM).

Familial predisposition to monoclonal gammopathies: deviations in B-cell biology.

Monoclonal gammopathies are associated with advancing age but a familial predisposition has been recognized for several decades. A functional phenotype, characterized by increased immunoglobulin (Ig) production after mitogen stimulation has been identified in healthy members of 4 families showing a predisposition toward IgM and IgG/IgA disorders. B cells from these hyperresponders do not show increased rates of Ig gene translocations and no aberrations were detected in an in vitro model of the germinal center reaction.

[Elective splenectomy at landspitali university hospital 1993-2004 efficacy and long-term outcome].

Objective: To evaluate the long-term outcome of elective splenectomy, with emphasis on the incidence of complications, vaccine immunization and patient´s knowledge about asplenia.

Material And Methods: Medical reports of all patients, who underwent elective splenectomy during the time period of 1993-2004, were reviewed. Questionnaire was sent to 96% (44/46) patients alive.

Familial paraproteinemia: hyper-responsive B-cells as endophenotype.

The prevalence of paraproteinemias or monoclonal gammopathies increases with age. No other major risk factors have been recognized, but significant associations have been reported with chronic antigen exposure, agricultural environment, and family history. In around 130 families reported worldwide, IgG or IgA monoclonal gammopathy of undetermined significance (MGUS) occurs with multiple myeloma (MM) whereas Waldenström's macroglobulinemia (WM) is linked to IgM MGUS.

Familial monoclonal gammopathy: hyper-responsive B cells in unaffected family members.

Background:   In Iceland, eight families have been identified with multiple cases of monoclonal gammopathies (MG) and other lymphoproliferative diseases. In one of these families with several cases of monoclonal gammopathy of undetermined significance (MGUS) and Waldenströms macroglobulinemia, in vitro stimulation with poke-weed mitogen revealed hyper-responsive B cells showing increased immunoglobulin production in one-third of disease-free family members.

Design And Methods:   In this study, the families were further traced and the list of names produced was compared with The Icelandic Cancer Registry (ICR) to find all recent cases of lymphoproliferative diseases.

Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm.

We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.

Familial predisposition to monoclonal gammopathy of unknown significance, Waldenström's macroglobulinemia, and multiple myeloma.

The medical literature contains reports of around 130 families with two or more cases of MM, MGUS, or WM. An Icelandic family with multiple cases of MGUS, WM, and lymphoma was first described in 1978. In vitro testing of peripheral blood lymphocytes revealed increased production of immunoglobulins in response to poke-weed mitogen in 10 out of 35 family members, referred to as hyperresponders (HR).

Monoclonal gammopathy: natural history studied with a retrospective approach.

The aim of this study was to examine the natural history of monoclonal gammopathy using a retrospective approach and a long observation period. Protein electrophoresis (PE) and immunofixation (IF) was performed on frozen prediagnosis serum samples from 65 multiple myeloma (MM) and 10 Waldenström's macroglobulinemia (WM) cases. Paraprotein was found in 28% and 46% of the samples from cases using PE and IF respectively.

[Severe adverse effects of quinine: Report of seven cases.].

Objective: Quinine is a drug which is mainly used for prevention of nocturnal leg cramps. Serious side effects of this drug have been described in recent years, including cytopenias and the hemolytic-uremic syndrome. We report seven cases of severe adverse effects of quinine.

[Scombroid poisoning at an Icelandic restaurant].

We report four cases of scombroid poisoning. During a lunch meeting three males had the same dish: a club sandwich with raw tuna. All developed erythema over the face and neck within two hours of eating the tuna.

Flt3/Flk-2 ligand in combination with thrombopoietin decreases apoptosis in megakaryocyte development.

The growth factors thrombopoietin (TPO) and Flt3/Flk-2-ligand (FL), either independently or in combination, modulate megakaryocyte development. Our results show that bone marrow CD34+ cells cultured with TPO and FL differentiate at a slower rate into CD41+ cells and are delayed in apoptosis at the later stages of the cultures compared to cells cultured with TPO alone. Our data also show that FL in synergy with TPO may inhibit apoptosis in megakaryocyte development by up-regulating bcl-2 and inducing conformational changes of p53, in MK progenitors.

Epidemiology of hairy cell leukemia in Iceland.

Introduction: Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disorder. Previous epidemiological studies have mainly focused on cases derived from single institutions or from localized cancer registries. This is the first study in which all cases diagnosed nationwide over a long period of time in a well defined population are analysed.

Monoclonal gammopathy in Iceland: a population-based registry and follow-up.

The term monoclonal gammopathy (MG) signifies the benign or malignant clonal growth of B lymphocytes. In the present study, monoclonal gammopathy of unknown significance (MGUS) was defined as those patients with no identified haematological malignancy. A database was constructed of all 713 MG patients in Iceland between 1976 and 1997 and compared with the Icelandic Cancer Registry.

Endocarditis caused by Lactococcus cremoris.

We describe a case of subacute endocarditis due to Lactococcus cremoris associated with consumption of unpasteurized milk. Treatment with amoxicillin-clavulanic acid and subsequently penicillin resulted in prompt sterilization of this patient's bloodstream and full recovery.

Flt3/Flk-2-ligand in synergy with thrombopoietin delays megakaryocyte development and increases the numbers of megakaryocyte progenitor cells in serum-free cultures initiated with CD34+ cells.

Megakaryocytopoiesis involves proliferation and maturation of committed precursors that increase their size by polyploidy, a process that is believed to be critical for the efficient production and release of platelets. Thrombopoietin has been shown to act on proliferation, maturation, and survival pathways in megakaryocytopoiesis. Less is known about the role of Flt3/Flk-2-ligand in this development.