👤 Atsushi Hirao

A 70-year-old woman with complaints of edema, general malaise, and hypotension was diagnosed with renal amyloidosis, and laser microdissection mass spectrometry revealed her amyloidosis to predominantly comprise the apolipoprotein A-IV type. The M-protein turned from negative to positive during the course, and a bone marrow biopsy showed smoldering myeloma. Treatment with bortezomib and dexamethasone failed to save her from heart failure six months after the onset. Western blotting of urine samples at the time of the renal biopsy showed that amyloid light-chain κ amyloidosis had been present since the onset. Unlike the myeloma, Congo red staining was positive in the plasma cells of the bone marrow. Show less

Biomarkers of Alzheimer's disease (AD) that can easily be measured in routine health checkups are desirable. Urine is a source of biomarkers that can be collected easily and noninvasively. We previously reported on the comprehensive profile of the urinary proteome of AD patients and identified proteins estimated to be significantly increased or decreased in AD patients by a label-free quantification method. The present study aimed to validate urinary levels of proteins that significantly differed between AD and control samples from our proteomics study (i.e., apolipoprotein C3 [ApoC3], insulin-like growth factor-binding protein 3 [Igfbp3], and apolipoprotein D [ApoD]). Enzyme-linked immunosorbent assays (ELISAs) were performed using urine samples from the same patient and control groups analyzed in the previous proteomics study (18 AD and 18 controls, set 1) and urine samples from an independent group of AD patients and controls (13 AD, 5 mild cognitive impairment [MCI], and 32 controls) from the National Center for Geriatrics and Gerontology Biobank (set 2). In set 1, the crude urinary levels of ApoD, Igfbp3, and creatinine-adjusted ApoD were significantly higher in the AD group relative to the control group ( ApoC3 may be a potential biomarker for AD, as validated by ELISA. Further analysis of ApoC3 as a urinary biomarker for AD is warranted. Show less

To describe the surgical placement of a continuous extraluminal tracheal prosthesis (CETP) and report the subsequent postoperative clinical outcomes in dogs with tracheal collapse. Retrospective case series. Fifty-four dogs. Medical records of dogs in which cervical and/or thoracic inlet tracheal collapse was diagnosed and treated by placement of a CETP between 2010 and 2017 were reviewed to evaluate postoperative complications, changes in respiratory function, and survival. Histological examinations of tracheal tissues performed in 2 dogs at 51 and 57 months after surgery were also reviewed. Fifty-three (98%) dogs survived to discharge. Postoperative complications included laryngeal paralysis (1 dog), disseminated intravascular coagulation (1 dog), and recurrent tracheal collapse (2 dogs). None of the dogs exhibited clinical evidence of tracheal necrosis. Preoperative dry, harsh cough resolved in 87% of the dogs after surgery. Goose honking cough was resolved in 25 of 26 (96%) dogs. Median follow-up time was 30 months (range, 16 days to 76 months). The survival rate at 36 months was 86% (CI: 75%-96%). On histological examination in 2 dogs, the tracheal tissue surrounding the prosthesis was well preserved and without evidence of chronic inflammation. Continuous extraluminal tracheal prosthesis placement in dogs with tracheal collapse resulted in low postoperative complication rates and good long-term outcomes. Continuous extraluminal tracheal prosthesis placement provides a viable alternative surgical option for managing dogs with tracheal collapse. Show less

Mammalian tribbles homolog 1 (TRIB1) regulates hepatic lipogenesis and is genetically associated with plasma triglyceride (TG) levels and cholesterol, but the molecular mechanisms remain obscure. We explored these mechanisms in mouse livers transfected with a TRIB1 overexpression, a shRNA template or a control (LacZ) adenovirus vector. The overexpression of TRIB1 reduced, whereas induction of the shRNA template increased, plasma glucose, TG, and cholesterol and simultaneously hepatic TG and glycogen levels. The involvement of TRIB1 in hepatic lipid accumulation was supported by the findings of a human SNP association study. A TRIB1 SNP, rs6982502, was identified in an enhancer sequence, modulated enhancer activity in reporter gene assays, and was significantly (P=9.39 × 10(-7)) associated with ultrasonographically diagnosed non-alcoholic fatty liver disease in a population of 5570 individuals. Transcriptome analyses of mouse livers revealed significant modulation of the gene sets involved in glycogenolysis and lipogenesis. Enforced TRIB1 expression abolished CCAAT/enhancer binding protein A (CEBPA), CEBPB, and MLXIPL proteins, whereas knockdown increased the protein level. Levels of TRIB1 expression simultaneously affected MKK4 (MAP2K4), MEK1 (MAP2K1), and ERK1/2 (MAPK1/3) protein levels and the phosphorylation of JNK, but not of ERK1/2. Pull-down and mammalian two-hybrid analyses revealed novel molecular interaction between TRIB1 and a hepatic lipogenic master regulator, MLXIPL. Co-expression of TRIB1 and CEBPA or MLXIPL reduced their protein levels and proteasome inhibitors attenuated the reduction. These data suggested that the modulation of TRIB1 expression affects hepatic lipogenesis and glycogenesis through multiple molecular interactions. Show less

PSD-95 is a component of postsynaptic densities in central synapses. It contains three PDZ domains that localize N-methyl-D-aspartate receptor subunit 2 (NMDA2 receptor) and K+ channels to synapses. In mouse forebrain, PSD-95 bound to the cytoplasmic COOH-termini of neuroligins, which are neuronal cell adhesion molecules that interact with beta-neurexins and form intercellular junctions. Neuroligins bind to the third PDZ domain of PSD-95, whereas NMDA2 receptors and K+ channels interact with the first and second PDZ domains. Thus different PDZ domains of PSD-95 are specialized for distinct functions. PSD-95 may recruit ion channels and neurotransmitter receptors to intercellular junctions formed between neurons by neuroligins and beta-neurexins. Show less