Cardioprotective effects of hyperkalemia during simulated ischemia/reperfusion in neonatal rat cardiomyocytes : Preservation of Na+/K+-ATPase activity

Background : Hyperkalemia has multimodal effects on myocardial protection during ischemia/reperfusion. The preservation of Na+/K+-ATPase activity induced by hyperkalemia may have critical impact on myocardial protection. Methods : To elucidate the roles of hyperkalemia (16 mM) and Na+/K+-ATPase inhibition (100 μMouabain) inmyocardial protection during simulated ischemia (5 mM NaCN and 5.5 mM 2-deoxyglucose)/ reperfusion, we measured loss of membrane integrity and bleb formation using a vital dye calcein AM in cultured neonatal rat cardiomyocytes. The control perfusate was switched to treatment solution for 15 min, followed by reperfusion for 30 min. In a second set of experiments, myocardial excitability and diastolic intracellular calcium ion concentration ([Ca2+]i) were measured during a 45-min treatment using a calcium-sensitive fluorescent dye fluo-4 AM. Results : Simulated ischemia/reperfusion under ouabain treatment induced loss of membrane integrity, which was suppressed by hyperkalemia. Simulated ischemia/reperfusion induced bleb formation, which was accelerated by ouabain. Hyperkalemia delayed and inhibited the increase in diastolic [Ca2+]i induced by simulated ischemia. Furthermore, hyperkalemia almost completely inhibited the effects of ouabain on the diastolic [Ca2+]i during ischemia. Conclusions : These results suggest that hyperkalemia during ischemia is cardioprotective against ischemia/reperfusion insults and that hyperkalemia inhibits the effects of ouabain during ischemia

Domoic acid in a bivalve Spondylus cruentus in Nha Trang Bay, Khanh Hoa Province, Vietnam

Recently we have found that domoic acid (DA), a toxin responsible for amnesic shellfish poisoning, is always detected in bivalve species belonging to a genus Spondylus randomly collected from various parts of the tropical areas including Vietnam. In Vietnam, 10 species of Spondylus are known to grow. Among these species, S. cruentus is a commercially valuable species. Domoic acid in S. cruentus collected in Nha Trang Bay is analyzed by ELISA and LC/MS/MS. Remarkable individual difference was observed in DA level among 28 specimens of S. cruentus collected from the same area at the same time. The DA level in S. cruentus apparently showed a seasonal variation. However, the variation of DA content seems to be due to a large individual difference among the specimens. When the specimens were reared in plankton-free conditions, DA level in S. cruentus did not decreaseds for 45 days, showing that S. cruentus maintains DA for a long period

Direct Observation of Site-specific Valence Electronic Structure at Interface: SiO2/Si Interface

Atom specific valence electronic structures at interface are elucidated successfully using soft x-ray absorption and emission spectroscopy. In order to demonstrate the versatility of this method, we investigated SiO2/Si interface as a prototype and directly observed valence electronic states projected at the particular atoms of the SiO2/Si interface; local electronic structure strongly depends on the chemical states of each atom. In addition we compared the experimental results with first-principle calculations, which quantitatively revealed the interfacial properties in atomic-scale.Comment: 4 pages, 3 figure

Low-grade B-cell lymphoma presenting primarily in the bone marrow

Cases of low-grade B-cell lymphoma presenting primarily in the bone marrow are rare, and its clinicopathology remains unclear. We retrospectively examined patients with low-grade B-cell lymphoma presenting primarily in the bone marrow. Fourteen patients met the inclusion criteria, including 5 with lymphoplasmacytic lymphoma (LPL), 3 with chronic lymphocytic leukemia/small lymphocytic lymphoma, 2 with follicular lymphoma (FL), and 4 with low-grade B-cell lymphoma not otherwise specified (LGBCL-NOS). The median age was 69.5 years (range, 42-89 years), and a slight male predominance was noted (9 men and 5 women, 1.8: 1). Immunohistochemically, all cases were positive for CD20. One case was positive for CD138. Both cases of FL were positive for CD10 and B-cell lymphoma 2 (BCL-2), and immunoglobulin heavy locus (IgH)/B-cell lymphoma 2 rearrangement was observed by fluorescence in situ hybridization. The myeloid differentiation primary response gene (88) leucine to proline mutation was observed in 3 of 5 LPL, 1 of 2 FL, and 2 of 4 LGBCL-NOS patients. Paraproteinemia was observed in 10 patients; IgM and IgG paraproteinemia were observed in 6 and 3 patients, respectively. In this patient series, 3 patients had died at a median follow-up of 36.5 months; the cause of death of 1 LPL patient was malignant lymphoma itself. Thus, low-grade B-cell lymphoma presenting primarily in the bone marrow has various subtypes, and approximately one-third of the patients had LGBCL-NOS. The immunophenotypic features and myeloid differentiation primary response gene (88) leucine to proline mutation data of LGBCL-NOS suggested that some cases present with characteristics similar to those of LPL or marginal zone lymphoma

Seasonal variation of paralytic and amnesic shellfish toxicities in bivalves and microalgae in Haiphong area, Vietnam

Monitoring survey was conducted to know the distribution and seasonal variation of PSP and ASP toxicities in bivalves and the abundance of toxic microalgae in Haiphong area, Vietnam. Sampling was carried out at the stations in Cat Ba and Do Son every two weeks from February 2002 to March 2004. Low levels of PSP and DA were detected in shellfish samples from both stations, showing seasonal and yearly variation. Toxicity of plankton samples also showed fluctuation, though the clear correlation could not be observed with the shellfish toxicities. HPLC or LC-MSMS analysis provided clear evidence of shellfish contamination with these toxins and indicated the existence of causative microalgae for these toxicities in this area. Several species of Alexandrium such as A. minutum, A. tamiyavanichii, A. ostenfeldii, A. tamarense were found, though the abundance of them was very low. On the other hand, massive bloom of Pseudo-nitzschia occurred in January at both stations. However, these blooms did not always cause the increase of DA level both in plankton and shellfish samples

Seasonal variation of paralytic and amnesic shellfish toxicities in bivalves and microalgae in Haiphong area, Vietnam

Monitoring survey was conducted to know the distribution and seasonal variation of PSP and ASP toxicities in bivalves and the abundance of toxic microalgae in Haiphong area, Vietnam. Sampling was carried out at the stations in Cat Ba and Do Son every two weeks from February 2002 to March 2004. Low levels of PSP and DA were detected in shellfish samples from both stations, showing seasonal and yearly variation. Toxicity of plankton samples also showed fluctuation, though the clear correlation could not be observed with the shellfish toxicities. HPLC or LC-MSMS analysis provided clear evidence of shellfish contamination with these toxins and indicated the existence of causative microalgae for these toxicities in this area. Several species of Alexandrium such as A. minutum, A. tamiyavanichii, A. ostenfeldii, A. tamarense were found, though the abundance of them was very low. On the other hand, massive bloom of Pseudo-nitzschia occurred in January at both stations. However, these blooms did not always cause the increase of DA level both in plankton and shellfish samples

De novo CD5-positive diffuse large B-cell lymphomas show high specificity for cyclin D2 expression

　D cyclins positively regulate the cell cycle and mediate the pathogenesis of some lymphomas. Cyclin D1 overexpression is the hallmark of mantle cell lymphoma, whereas cyclins D2 and D3 are reportedly not as specific to certain lymphomas as cyclin D1. In this study, cyclin D2 was found to be overexpressed in 98% of de novo CD5-positive diffuse large B-cell lymphomas (DLBCLs) (50/51) and in 28% of CD5-negative DLBCLs (14/51). A statistically significant difference was observed between these two groups (p<0.0001). In contrast, no statistical difference was found in the cyclin D3 expression between CD5-positive (18/51) and CD5-negative (24/51) DLBCLs (p=0.23). Based on these findings, cyclin D2 is therefore considered to be closely associated with de novo CD5-positive DLBCLs. This insight may be useful for overcoming the inferior survival of this aggressive lymphoma

Rapid Acquisition of Alectinib Resistance in ALK-Positive Lung Cancer With High Tumor Mutation Burden

Introduction The highly selective ALK receptor tyrosine kinase (ALK) inhibitor alectinib is standard therapy for ALK-positive lung cancers; however, some tumors quickly develop resistance. Here, we investigated the mechanism associated with rapid acquisition of resistance using clinical samples. Methods Autopsied samples were obtained from lung, liver, and renal tumors from a 51-year-old male patient with advanced ALK-positive lung cancer who had acquired resistance to alectinib in only 3 months. We established an alectinib-resistant cell line (ABC-14) from pleural effusion and an alectinib/crizotinib-resistant cell line (ABC-17) and patient-derived xenograft (PDX) model from liver tumors. Additionally, we performed next-generation sequencing, direct DNA sequencing, and quantitative real-time reverse transcription polymerase chain reaction. Results ABC-14 cells harbored no ALK mutations and were sensitive to crizotinib while also exhibiting MNNG HOS transforming gene (MET) gene amplification and amphiregulin overexpression. Additionally, combined treatment with crizotinib/erlotinib inhibited cell growth. ABC-17 and PDX tumors harbored ALK G1202R, and PDX tumors metastasized to multiple organs in vivo, whereas the third-generation ALK-inhibitor, lorlatinib, diminished tumor growth in vitro and in vivo. Next-generation sequencing indicated high tumor mutation burden and heterogeneous tumor evolution. The autopsied lung tumors harbored ALK G1202R (c. 3604 G>A) and the right renal metastasis harbored ALK G1202R (c. 3604 G>C); the mutation thus comprised different codon changes. Conclusions High tumor mutation burden and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. Timely lorlatinib administration or combined therapy with an ALK inhibitor and other receptor tyrosine-kinase inhibitors might constitute a potent strategy