Citations

BACKGROUND Exposure to high altitude (HA) results in sympathetic nervous system (SNS) activation. This might interact with HA related illness. HRV is a technique to quantify SNS and parasympathetic nervous system (PNS) interactions and thus offers a noninvasive index in extreme environments. OBJECTIVE To quantify the changes in HRV in elite athletes (AT), acclimatized for 2 mo. at Everest base camp (BC) prior to summiting, relative to a control group (CT) (climbing and acclimatizing to BC in 3 wks). METHODS AT (N=4, Age=35±10 y, BMI=22±2, M/F ratio 2/2) and CT (N=8, Age=35±10 y, BMI=26±2, M/F ratio 8/0) performed autonomic tests consisting of quiet breathing, paced breathing prior to, mid‐way at BC and at 2 wks post expedition. RESULTS At BC, AT had (compared to CT) higher HR (p=0.07) and reduced HRV (SDNN, p=0.09). For AT and CT combined: measures of HRV were reduced at BC (SDNN, p=0.05, Poincare length, p=0.05) and remained below baseline 2 wks post climb (SDNN, p=0.01; PCL, p=0.01). CONCULSION HRV is reduced with HA exposure in both AT and CT and remains reduced 2 wks post exposure, suggesting either SNS activation and/or PNS withdrawal. FUNDING : Mayo Clinic & The North Face.

AbstractMultiple myeloma (MM) is a B-lineage malignancy characterized by diverse genetic subtypes and clinical outcomes. The recurrent immunoglobulin heavy chain (IgH) switch translocation, t(4;14)(p16;q32), is associated with poor outcome, though the mechanism is unclear. Quantitative reverse-transcription–polymerase chain reaction (RT-PCR) for proposed target genes on a panel of myeloma cell lines and purified plasma cells showed that only transcripts originating from the WHSC1/MMSET/NSD2 gene are uniformly dysregulated in all t(4;14)POS patients. The different transcripts detected, multiple myeloma SET domain containing protein (MMSET I), MMSET II, Exon 4a/MMSET III, and response element II binding protein (RE-IIBP), are produced by alternative splicing and alternative transcription initiation events. Translation of the various transcripts, including those from major breakpoint region 4-2 (MB4-2) and MB4-3 breakpoint variants, was confirmed by transient transfection and immunoblotting. Green fluorescent protein (GFP)–tagged MMSET I and II, corresponding to proteins expressed in MB4-1 patients, localized to the nucleus but not nucleoli, whereas the MB4-2 and MB4-3 proteins concentrate in nucleoli. Cloning and localization of the Exon 4a/MMSET III splice variant, which contains the protein segment lost in the MB4-2 variant, identified a novel protein domain that prevents nucleolar localization. Kinetic studies using photobleaching suggest that the breakpoint variants are functionally distinct from wild-type proteins. In contrast, RE-IIBP is universally dysregulated and also potentially functional in all t(4;14)POS patients irrespective of fibroblast growth factor receptor 3 (FGFR3) expression or breakpoint type.