Acute coronary syndrome after liver transplantation in a young primary biliary cholangitis recipient with dyslipidemia: a case report

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic, progressive liver disease associated with dyslipidemia. There is a consensus that PBC does not accelerate coronary artery disease despite high cholesterol levels, so the screening test for the coronary artery is not routinely performed before liver transplantation (LT). To date, no report has described the potential risk of PBC-related dyslipidemia for developing acute coronary syndrome (ACS) after LT. CASE PRESENTATION: A 40-year-old Asian female with a known history of PBC underwent ABO-incompatible living-donor LT, with her husband as the donor. Although she had high cholesterol and triglyceride levels that were refractory to medications, she passed all routine preoperative examinations, including cardiopulmonary function tests and infection screenings. One week after LT, she developed ACS with 90% stenosis of both the left anterior descending artery and left circumflex artery. Emergent stent implantation was successfully performed followed by dual antiplatelet therapy. The long history of PBC and associated severe dyslipidemia for 10 years would have accelerated the atherosclerosis, causing latent stenosis in the coronary artery. Inapparent stenosis might have become apparent due to unstable hemodynamics during the acute phase after LT. CONCLUSIONS: PBC-related dyslipidemia potentially brings a risk for developing ACS after LT. This experience suggests that the preoperative evaluation of the coronary artery should be considered for high-risk patients, especially those who have drug-resistant dyslipidemia

HSP47 in lung fibroblasts is a predictor of survival in fibrotic nonspecific interstitial pneumonia.

BACKGROUND: The histopathologic pattern is currently the most important prognostic marker for idiopathic interstitial pneumonia (IIP). However, more highly sensitive markers are now required. Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagens, and it has been demonstrated that HSP47 expression is significantly higher in the lung specimens of idiopathic UIP than in UIP associated with collagen vascular diseases (CVD). However, its expression in nonspecific interstitial pneumonia (NSIP), the other common pathological pattern of IIP, has not been well investigated. Therefore, the association between lung fibroblast HSP47 expression and prognosis in fibrotic NSIP was evaluated. METHODS: Surgical lung biopsy specimens of 63 patients [idiopathic fibrotic NSIP=19, fibrotic NSIP associated with CVD=9, idiopathic UIP=26, and UIP associated with CVD=9] were reviewed, and a score for lung fibroblast HSP47 expression was assigned. These patients\u27 clinical features and survival were also analyzed. RESULTS: There was no significant difference in HSP47 expression between idiopathic fibrotic NSIP and fibrotic NSIP associated with CVD. The idiopathic fibrotic NSIP patients with higher HSP47 expression levels in their lung specimens had a poorer prognosis than patients with lower HSP47 expression levels. CONCLUSIONS: The present results suggest that lung fibroblast HSP47 expression may be a useful new prognostic marker for idiopathic fibrotic nonspecific interstitial pneumonia

Treating patients in a trauma room equipped with computed tomography and patients’ mortality: a non-controlled comparison study

Abstract Background To improve acute trauma care workflow, the number of trauma centers equipped with a computed tomography (CT) machine in the trauma resuscitation room has increased. The effect of the presence of a CT machine in the trauma room on a patient’s outcome is still unclear. This study evaluated the association between a CT machine in the trauma room and a patient’s outcome. Methods Our study included all trauma patients admitted to a trauma center in Yokohama, Japan, between April 2014 and March 2016. We compared 140 patients treated using a conventional resuscitation room with 106 patients treated in new trauma rooms equipped with a CT machine. Results For the group treated in a trauma room with a CT machine, the Injury Severity Score (13.0 vs. 9.0; p = 0.002), CT scans of the head (78.3 vs. 66.4%; p = 0.046), CT scans of the body trunk (75.5 vs. 58.6%; p = 0.007), intubation in the emergency department (48.1 vs. 30.7%; p = 0.008), and multiple trauma patients (47.2 vs. 30.0%; p = 0.008) were significantly higher and Trauma and Injury Severity Score probability of survival (96.75 vs. 97.80; p = 0.009) was significantly lower than the group treated in a conventional resuscitation room. In multivariate analysis and propensity score matched analysis, being treated in a trauma room with a CT machine was an independent predictor for fewer hospital deaths (odds ratio 0.002; 95% CI 0.00–0.75; p = 0.04, and 0.07; 0.00–0.98, respectively). Conclusions Equipping a trauma room with a CT machine reduced the time in decision-making for treating a trauma patient and subsequently lowered the mortality of trauma patients

Yak1p, a DYRK family kinase, translocates to the nucleus and phosphorylates yeast Pop2p in response to a glucose signal

POP2 protein of Saccharomyces cerevisiae is a component of a protein complex that regulates the transcription of many genes. We found that the 97th threonine residue (Thr 97) of Pop2p was phosphorylated upon glucose limitation. The Thr 97 phosphorylation occurred within 2 min after removing glucose and was reversed within 1 min after the readdition of glucose. The effects of hexokinase mutations and glucose analogs indicate that this phosphorylation is dependent on glucose phosphorylating activity. We purified a protein kinase that phosphorylates a peptide containing Thr 97 of Pop2p and identified it as Yak1p, a DYRK family kinase. Phosphorylation of Pop2p was barely detectable in a yak1Δ strain. We found that Yak1p interacted with Bmh1p and Bmh2p only in the presence of glucose. A GFP-Yak1p fusion protein shuttled rapidly between the nucleus and the cytoplasm in response to glucose. A strain with alanine substituted for Thr 97 in Pop2p showed overgrowth in the postdiauxic transition and failed to stop the cell cycle at G(1) phase in response to glucose deprivation. Thus, Yak1p and Pop2p are part of a novel glucose-sensing system in yeast that is involved in growth control in response to glucose availability

Mammalian Bcnt/Cfdp1, a potential epigenetic factor characterized by an acidic stretch in the disordered N-terminal and Ser250 phosphorylation in the conserved C-terminal regions

The BCNT (Bucentaur) superfamily is classified by an uncharacteristic conserved sequence of ∼80 amino acids (aa)at the C-terminus, BCNT-C (the conserved C-terminal region of Bcnt/Cfdp1). Whereas the yeast Swc5 and DrosophilaYeti homologues play crucial roles in chromatin remodelling organization, mammalian Bcnt/Cfdp1 (craniofacialdevelopmental protein 1) remains poorly understood. The protein, which lacks cysteine, is largely disordered andcomprises an acidic N-terminal region, a lysine/glutamic acid/proline-rich 40 aa sequence and BCNT-C. It showscomplex mobility on SDS/PAGE at ∼50 kDa, whereas its calculated molecular mass is ∼33 kDa. To characterize thismobility discrepancy and the effects of post-translational modifications (PTMs), we expressed various deleted His–Bcnt in E. coli and HEK cells and found that an acidic stretch in the N-terminal region is a main cause of the gel shift.Exogenous BCNT/CFDP1 constitutively expressed in HEK clones appears as a doublet at 49 and 47 kDa, slower thanthe protein expressed in Escherichia coli but faster than the endogenous protein on SDS/PAGE. Among seven in vivophosphorylation sites, Ser250, which resides in a region between disordered and ordered regions in BCNT-C, is heavilyphosphorylated and detected predominantly in the 49 kDa band. Together with experiments involving treatment withphosphatases and Ser250 substitutions, the results indicate that the complex behaviour of Bcnt/Cfdp1 on SDS/PAGEis caused mainly by an acidic stretch in the N-terminal region and Ser250 phosphorylation in BCNT-C. Furthermore,Bcnt/Cfdp1 is acetylated in vitro by CREB-binding protein (CBP) and four lysine residues including Lys268 in BCNT-Care also acetylated in vivo, revealing a protein regulated at multiple levels

Title: Mammalian Bcnt/Cfdp1, a potential epigenetic factor characterized by an acidic stretch in the disordered N-terminal and S250 phosphorylation in the conserved C-terminal regions

Abstract The BCNT superfamily is classified by an uncharacteristic conserved sequence of ~80 amino acids (aa) at the C-terminus, BCNT-C. Whereas the yeast Swc5 and Drosophila Yeti homologs play crucial roles in chromatin remodeling organization, mammalian Bcnt/Cfdp1 remains poorly understood. The protein, which lacks Cys, is largely disordered, and comprises an acidic N-terminal region, a Lys/Glu/Pro-rich 40 aa sequence, and BCNT-C. It shows complex mobility on SDS-PAGE at ~50 kDa, whereas its calculated molecular mass is ~33 kDa. To characterize this mobility discrepancy and the effects of post-translational modifications, we expressed various deleted His-Bcnt in E. coli and HEK cells, and found that an acidic stretch in the N-terminal region is a main cause of the gel shift. Exogenous BCNT/CFDP1 constitutively expressed in HEK clones appears as a doublet at 49 and 47 kDa, slower than the protein expressed in E. coli but faster than the endogenous protein on SDS-PAGE. Among seven in vivo phosphorylation sites, S250, which resides in a region between disordered and ordered regions in BCNT-C, is heavily phosphorylated and detected predominantly in the 49 kDa band. Together with experiments involving treatment with phosphatases and S250 substitutions, the results indicate that the complex behavior of Bcnt/Cfdp1 on SDS-PAGE is caused mainly by an acidic stretch in the N-terminal region and S250 phosphorylation in BCNT-C. Furthermore, Bcnt/Cfdp1 is acetylated in vitro by CREB-binding protein, and four Lys residues including K268 in BCNT-C are also acetylated in vivo, revealing a protein regulated at multiple levels