Decreased level of phosphatidylcholine (16:0/20:4) in multiple myeloma cells compared to plasma cells: a single-cell MALDI-IMS approach.

Lipid metabolic changes under diseased conditions, particularly in solid tumors, are attracting increased attention. However, in non-solid tumors, including most hematopoietic tumors, lipid analyses are scarce. Multiple myeloma (MM) is a plasma cell disorder arising from bone marrow, and the lipid status of MM cells has not been reported yet. In this study, we analyzed flow cytometry-sorted single MM cells and normal plasma cells (NPCs) using matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS), a two-dimensional label-free mass spectrometry technique for biomolecular analysis, to obtain specific lipid information. We isolated 1.31-5.77% of MM cells and 0.03-0.24% of NPCs using fluorescence-activated cell sorting (FACS). Analysis of purified cells using MALDI-IMS at the single-cell level revealed that the peak intensity and ion signals of phosphatidylcholine [PC (16:0/20:4) + H](+) at m/z 782.5 were significantly decreased in MM cells compared to NPCs. By examining particular cell populations rather than cell mixtures, our method can become a suitable tool for the analysis of rare cell populations at the single-cell level and advance the understanding of MM progression.

Relevance of cardiomyocyte mechano-electric coupling to stretch-induced arrhythmias: optical voltage/calcium measurement in mechanically stimulated cells, tissues and organs.

Stretch-induced arrhythmias are multi-scale phenomena in which alterations in channel activities and/or calcium handling lead to the organ level derangement of the heart rhythm. To understand how cellular mechano-electric coupling (MEC) leads to stretch-induced arrhythmias at the organ level, we developed stretching devices and optical voltage/calcium measurement techniques optimized to each cardiac level. This review introduces these experimental techniques of (1) optical voltage measurement coupled with a carbon-fiber technique for single isolated cardiomyocytes, (2) optical voltage mapping combined with motion tracking technique for myocardial tissue/whole heart preparations and (3) real-time calcium imaging coupled with a laser optical trap technique for cardiomyocytes. Following the overview of each methodology, results are presented. We conclude that individual MEC in cardiomyocytes can be heterogeneous at the ventricular level, especially when moderate amplitude mechanical stretches are applied to the heart, and that this heterogeneous MEC can evoke focal excitation that develops into re-entrant arrhythmias.

Intravascular large B-cell lymphoma manifesting as cholecystitis: report of an Asian variant showing gain of chromosome 18 with concurrent deletion of chromosome 6q.

Intravascular large B-cell lymphoma (IVLBCL), which involves the lumen of small vessels, is a rare variant of extranodal diffuse large B-cell lymphomas. Herein, we present a case of IVLBCL manifesting as cholecystitis in a 77-year-old Japanese man. He presented with fever, fatigue, and weight loss. Physical examination revealed tenderness of the right upper quadrant. The white blood cell count and C-reactive protein levels were elevated. Computed tomography revealed gallbladder thickening and pericholecystic fluid collection; these observations were consistent with the diagnosis of cholecystitis. Serum soluble interleukin-2 receptor levels were highly elevated, and gallium scintigraphy revealed an abnormal accumulation in the spleen, implying lymphoma. Consequently, G-banding analysis of the patient's bone marrow aspirates revealed the presence of different abnormal clones, including those with gain of chromosome 18 and deletion of chromosome 6q. As cholecystectomy was necessary, a concurrent splenectomy was performed to diagnose the disease definitively. Histopathologically, atypical large lymphoid cells were observed to be localized in the vasculature in both the spleen and gallbladder; the atypical cells expressed high levels of CD20, CD5, and CD10, immunohistochemically. These findings were consistent with IVLBCL. The patient underwent post-operative treatment with rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone. However, a pancreatic fistula developed during chemotherapy, causing left pleural effusion and peritoneal effusion; the patient developed sepsis from multidrug-resistant microorganisms, and subsequently died of multi-organ failure 6 months after the diagnosis. No obvious recurrence of the tumor was found during autopsy. We discuss the characteristic karyotype and immunohistochemical status observed in this case.