赤芽球癆を合併したT-cell large granular lymphocyte leukemia の一例

T-cell large granular lymphocyte leukemia は長期(6か月以上)にわたる末梢血中の著明な大顆粒リンパ球(large granular lymphocyte;以下,LGL)のモノクローナルな増加によって特徴づけられる疾患で,しばしば赤芽球癆を伴うことが知られている.今回,我々はHCV陽性肝硬変患者に赤芽球癆を合併したT-LGLの1例を経験した.末梢血および骨髄塗抹標本では細胞質内に微細なアズール顆粒を有し,核異型を示すリンパ球の増加がみられ,末梢血および骨髄のフローサイトメトリーおよび骨髄吸引クロット標本の免疫組織化学で,CD3,CD8,CD57陽性リンパ球の増加が確認された.骨髄細胞のPCRではTCRβの再構成を認めず,TCRγおよびTCRδの再構成がみられた.またプレドニゾロン治療にてCD57陽性リンパ球の減少および赤芽球造血の回復が確認されたことから,赤芽球癆を合併したγδT-LGLと診断した.最近,T-LGLにはSTAT3あるいはSTAT5bのSHドメインの遺伝子変異が高頻度にみられることが報告されているが,本症例においては,これらの遺伝子変異は確認できなかった.T-cell large granular lymphocytic leukemia (T-LGL) is characterized by marked increase of monoclonal large granular lymphocytes (LGL) in the peripheral blood over the long term (6 months or more). It has been reported about 20% cases of T-LGL cases are associated with pure red cell aplasia (PRCA). Here, we describe a case of T-LGL associated with PRCA. This case was characterized by increase in the number of CD3+,CD8+,CD57+, and granzyme B-positive lymphocytes with fine azurophilic cytoplasmic granules and nuclear atypia in peripheral blood and bone marrow. The patient was diagnosed havingγδT-LGL because T-cell receptor (TCR)γ and TCRδ gene but not TCRβ gene rearrangement was detected by the PCR of the bone marrow cells. Prednisolone administration decreased in number of the LGL cells, accompanying recover of erythropoiesis. Although somatic mutations in the Src homology 2 domain of STAT3 or STAT5b gene are reported in 70% percent of the T-LGL with PRCA, such STAT mutations could not be detected in this case

Proteomics analysis of heterogeneous flagella in brown algae (stramenopiles).

International audienceFlagella are conserved organelles among eukaryotes and they are composed of many proteins, which are necessary for flagellar assembly, maintenance and function. Stramenopiles, which include brown algae, diatoms and oomycetes, possess two laterally inserted flagella. The anterior flagellum (AF) extends forward and bears tripartite mastigonemes, whilst the smooth posterior flagellum (PF) often has a paraflagellar body structure. These heterogeneous flagella have served as crucial structures in algal studies especially from a viewpoint of phylogeny. However, the protein compositions of the flagella are still largely unknown. Here we report a LC-MS/MS based proteomics analysis of brown algal flagella. In total, 495 flagellar proteins were identified. Functional annotation of the proteome data revealed that brown algal flagellar proteins were associated with cell motility, signal transduction and various metabolic activities. We separately isolated AF and PF and analyzed their protein compositions. This analysis led to the identification of several AF- and PF-specific proteins. Among the PF-specific proteins, we found a candidate novel blue light receptor protein involved in phototaxis, and named it HELMCHROME because of the steering function of PF. Immunological analysis revealed that this protein was localized along the whole length of the PF and concentrated in the paraflagellar body

Long-term policies for electrical generating capacity in Argentina

LD:D45379/83 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Dense radical formation in L-alanine-3,3,3-d3 and L-alanine-d4 by 1.5 keV soft X-ray irradiation

Radicals produced in crystalline L-alanine-3,3,3-d3 and L-alanine-d4 were observed by the electron spin reso-nance (ESR) technique during 1.5 keV soft X-ray irradiation. The spectral change from •CHCD3COOH to •CDCD3COOH by a hydrogen exchange reaction was directly observed in L-alanine-3,3,3-d3. The line width of the ESR spectra obtained by the soft X-ray irradiation was 1.5 times wider than that of hard X-rays from a previous report, meaning a higher density of radicals

Lenalidomide and Dexamethasone for a Patient of POEMS Syndrome Presenting with Massive Ascites

POEMS syndrome is a multisystem disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. POEMS syndrome is a rare cause of refractory ascites. We report the case of a patient with POEMS syndrome presenting with massive ascites who was treated with very-low-dose lenalidomide and dexamethasone. A 57-year-old Japanese man was admitted to our hospital with pleural effusion, massive ascites, and leg edema. The diagnosis of POEMS syndrome was made based on the combination of the following findings: peripheral neuropathy, organomegaly, endocrinopathy, serum monoclonal protein elevation, skin changes, plasma VEGF elevation, and evidence of extravascular volume overload. Renal dysfunction induced by biopsy-proven renal involvement of POEMS syndrome was observed. Massive ascites of the patient dramatically diminished with long-time treatment of very-low-dose lenalidomide and dexamethasone. Lenalidomide seems to be a very promising therapy for POEMS syndrome presenting with extravascular volume overload such as edema, pleural effusion, and ascites. Very-low-dose lenalidomide might be effective especially for the patients with POEMS-related nephropathy

A Novel SCN5A Gain-of-Function Mutation M1875T Associated With Familial Atrial Fibrillation

ObjectivesThis study describes a novel heterozygous gain-of-function mutation in the cardiac sodium (Na+) channel gene, SCN5A, identified in a Japanese family with lone atrial fibrillation (AF).BackgroundSCN5A mutations have been associated with a variety of inherited arrhythmias, but the gain-of-function type modulation in SCN5A is associated with only 1 phenotype, long-QT syndrome type 3 (LQTS3).MethodsWe studied a Japanese family with autosomal dominant hereditary AF, multiple members of which showed an onset of AF or frequent premature atrial contractions at a young age.ResultsThe 31-year-old proband received radiofrequency catheter ablation, during which time numerous ectopic firings and increased excitability throughout the right atrium were documented. Mutational analysis identified a novel missense mutation, M1875T, in SCN5A. Further investigations revealed the familial aggregation of this mutation in all of the affected individuals. Functional assays of the M1875T Na+ channels using a whole-cell patch-clamp demonstrated a distinct gain-of-function type modulation; a pronounced depolarized shift (+16.4 mV) in V1/2 of the voltage dependence of steady-state inactivation; and no persistent Na+ current, which is a defining mechanism of LQTS3. These biophysical features of the mutant channels are potentially associated with increased atrial excitability and normal QT interval in all of the affected individuals.ConclusionsWe identified a novel SCN5A mutation associated with familial AF. The mutant channels displayed a gain-of-function type modulation of cardiac Na+ channels, which is a novel mechanism predisposing to increased atrial excitability and familial AF. This is a new phenotype resulting from the SCN5A gain-of-function mutations and is distinct from LQTS3