[Comparison of single infusion of anti-BCMA versus combined infusion of anti-CD19 chimeric antigen receptor T cells for immune reconstruction in relapsed/refractory multiple myeloma].

Objective: We observed and compared the differences in immune reconstruction between single-infusion anti-B-cell maturation antigen (BCMA) , chimeric antigen receptor T cells (CAR-T) , and combined infusion of anti-CD19 CAR-T cells in the treatment of recurrent/refractory multiple myeloma (RRMM) . Methods: Sixty-one patients with RRMM who underwent CAR-T cell therapy in our hospital from June 2017 to December 2020 were selected. Among them, 26 patients received anti-BCMA target, and 35 patients received anti-BCMA combined with anti-CD19 target. Using flow cytometry, we determined T cell subsets (CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+)) , B cells (CD19(+)) , and NK cells (CD16(+) CD56(+)) at different time points before and after CAR-T treatment, and detected immunoglobulin IgG, IgA and IgM levels by immunoturbidimetry. We compared the reconstruction rules of lymphocyte subsets and immunoglobulins in the two groups. Results: CD8(+) T lymphocytes recovered most rapidly after the infusion of CAR-T cells, returning to pre-infusion levels at 3 months and 1 month after infusion, respectively[BCMA: 695 (357, 1264) /µl vs 424 (280, 646) /µl; BCMA+CD19: 546 (279, 1672) /µl vs 314 (214, 466) /µl]. NK cells returned to normal levels at 3 months after infusion in both groups[BCMA: 171 (120, 244) /µl, BCMA+CD19: 153 (101, 218) /µl (Normal reference range 150-1100/µl) ]; however, the NK cells were not maintained at stable levels in the BCMA CAR-T cells group. The recovery of CD4(+) T lymphocytes in both groups was slow and remained persistently low within 12 months after infusion, and no recovery was observed in most patients. The reversal of the ratio of CD4(+)/CD8(+) lasted for more than a year. The levels of CD19(+) B cells in both groups returned to baseline 3 months after infusion[BCMA: 62 (10, 72) /µl vs 57 (24, 78) /µl; BCMA+CD19: 40 (4, 94) /µl vs 29 (14, 46) /µl]. IgG returned to the pre-infusion level 12 months after infusion in the group with anti-BCMA cells alone, but not in the group with combined infusion of CD19 CAR T cells[7.82 (6.03, 9.64) g/L vs 6.92 (4.62, 12.76) g/L]. IgA returned to pre-infusion levels at 9 and 12 months after infusion, respectively[BCMA: 0.46 (0.07, 0.51) g/L vs 0.22 (0.12, 4.01) g/L; BCMA+CD19: 0.46 (0.22, 0.98) g/L vs 0.27 (0.10, 0.53) g/L]. IgM in both groups returned to pre-infusion levels 6 months after infusion[BCMA: 0.43 (0.06, 0.60) g/L vs 0.20 (0.13, 0.37) g/L; BCMA+CD19: 0.53 (0.10, 0.80) g/L vs 0.16 (0.11, 0.28) g/L]. There was no significant difference in the indexes of lymphocyte subpopulation reconstruction and immunoglobulin recovery between the two groups at each time point. Conclusion: This study showed that in patients with RRMM treated with CAR-T cells, the appropriate target antigen can be selected without considering the difference of immune reconstruction between anti-BCMA CAR-T and combined anti-CD19 CAR-T therapy.

Introduction to The neurosciences and music IV: learning and memory.

The conference entitled "The Neurosciences and Music-IV: Learning and Memory'' was held at the University of Edinburgh from June 9-12, 2011, jointly hosted by the Mariani Foundation and the Institute for Music in Human and Social Development, and involving nearly 500 international delegates. Two opening workshops, three large and vibrant poster sessions, and nine invited symposia introduced a diverse range of recent research findings and discussed current research directions. Here, the proceedings are introduced by the workshop and symposia leaders on topics including working with children, rhythm perception, language processing, cultural learning, memory, musical imagery, neural plasticity, stroke rehabilitation, autism, and amusia. The rich diversity of the interdisciplinary research presented suggests that the future of music neuroscience looks both exciting and promising, and that important implications for music rehabilitation and therapy are being discovered.

Functional complementation of yeast vma1 delta cells by a plant subunit A homolog rescues the mutant phenotype and partially restores vacuolar H(+)-ATPase activity.

The ability of a vacuolar H(+)-ATPase (V-ATPase) subunit homolog (subunit A) from plants to rescue the vma mutant phenotype of yeast was investigated as a first step towards investigating the structure and function of plant subunits in molecular detail. Heterologous expression of cotton cDNAs encoding near-identical isoforms of subunit A in mutant vma1 delta yeast cells successfully rescued the mutant vma phenotype, indicating that subunit A of plants and yeast have retained elements essential to V-ATPases during the course of evolution. Although vacuoles become acidified, the plant-yeast hybrid holoenzyme only partially restored V-ATPase activity (approximately 60%) in mutant yeast cells. Domain substitution of divergent N- or C-termini only slightly enhanced V-ATPase activity, whereas swapping both domains acted synergistically, increasing coupled ATP hydrolysis and proton translocation by approximately 22% relative to the native plant subunit. Immunoblot analysis indicated that similar amounts of yeast, plant or plant-yeast chimeric subunits are membrane-bound. These results suggest that subunit A terminal domains contain structural information that impact V-ATPase structure and function.

Hemolysins and plasmid profiles of Vibrio parahaemolyticus.

Forty clinical isolates of Vibrio parahaemolyticus were studied for the production of the thermostable direct hemolysin (TDH), and the TDH-related hemolysin (TRH) including the respective encoding genes, tdh and trh. The presence of TDH and its encoding genes were found amongst 95% of the strains, whereas the TRH was absent amongst these isolates. Thirty-two isolates were found to be plasmid-free, whereas eight isolates possessed plasmids with sizes ranging from 2.4 > or = 23 kb. Using a DNA probe coding for the homologous region of the tdh and trh, it was found that the tdh genes were present on the chromosomal DNA.

A modified hot borate method significantly enhances the yield of high-quality RNA from cotton (Gossypium hirsutum L.).

The isolation of biologically active RNA from cotton (Gossypium hirsutum L.) is difficult due to interference by high levels of endogenous phenolics, polysaccharides, and secondary metabolites. A modified hot borate procedure was developed to combat these cellular constituents during tissue homogenization, resulting in the quantitative recovery of RNA suitable for hybridization analysis, in vitro translation, and cDNA synthesis. The efficacy of several hot borate buffer adjuvants for the qualitative and quantitative recovery of leaf RNA was monitored by absorbance spectra, gel electrophoresis, protein, and cDNA synthesis. Of the buffer adjuvants evaluated, polyvinylpyrrolidone-40 (PVP-40) exhibited the single, most significant impact on the yield and quality of RNA isolated from cotton leaves, although inclusion of deoxycholate and/or Nonident-40 (NP-40) further enhanced the quality of the RNA. The unsurpassed qualitative and quantitative recovery of total RNA from cotton by hot borate buffer at alkaline pH, supplemented with PVP-40, deoxycholate, and/or NP-40 had also proven satisfactory for other recalcitrant plant species as well as for especially difficult tissue types.

Ancient origin of the vacuolar H(+)-ATPase 69-kilodalton catalytic subunit superfamily.

Recently, two distinct cDNA clones encoding the catalytic subunit of the vacuolar H(+)-ATPase (V-ATPase) were isolated from the allotetraploid cotton species Gossypium hirsutum L. cv 'Acala SJ-2' (Wilkins 1992, 1993). Differences in the nucleotide sequence of these clones were used as molecular markers to explore the organization and structure of the V-ATPase catalytic subunit genes in the A and D genomes of diploid and allotetraploid cotton species. Nucleotide sequencing of polymerase chain reaction (PCR) products amplified from G. arboreum (A2, 2n=26), G. raimondii (D5, 2n=26), and G. hirsutum cv 'Acala SJ-2' [(AD)1, 2n=4x=52] revealed a V-ATPase catalytic subunit organization more complex than indicated hitherto in any species, including higher plants. In the genus Gossypium, the V-ATPase catalytic subunit genes are organized as a superfamily comprising two diverse but closely related multigene families, designated as vat69A and vat69B, present in both diploid and allotetraploid species. As expected, each vat69 subfamily is correspondingly more complex in the allotetraploid species due to the presence of both A and D alloalleles. Because of this, about one-half of the complex organization of V-ATPase catalytic subunit genes predates polyploidization and speciation of New World tetraploid species. Comparison of plant and fungal V-ATPase catalytic subunit gene structure indicates that introns accrued in the plant homologs following the bifurcation of plant and fungi but prior to the gene duplication event that gave rise to the vat69A and vat69B genes approximately 45 million years ago. The structural complexity of plant V-ATPase catalytic subunit genes is highly conserved, indicating the presence of at least ten introns dispersed throughout the coding region.

Epithelioid leiomyosarcoma of the breast: report of a case.

A 36-year-old female presented with a palpable mass in the right breast. She received a modified radical mastectomy after admission. Brain and multiple bony metastases were noted 10 months later. Microscopically, the tumor was composed of nodules of small spindle and large round cells showing abundant eosinophilic, vacuolated cytoplasm and prominent nucleoli. No glandular or ductular differentiation could be identified. By immunohistochemistry, the tumor cells were positive for vimentin and desmin in focal areas, but negative for cytokeratin, S-100, epithelial membrane antigen, actin, myoglobin, or alpha-1-antichymotrypsin. Electron microscopy showed focally cohesive large cells maintained together by poorly-defined intercellular junctions and surrounded segmentally by thin basal laminae. Intracytoplasmic filaments were identified in some tumor cells, diffusely arranged in the cytoplasm. These findings indicate that this was a case of epithelioid leiomyosarcoma of the breast. The literature concerning this rare neoplasm is reviewed.