The reactions of (phenylsulfinyl)furans or -thiophenes with carbon nucleophiles in the presence of trifluoroacetic anhydride allowed the nucleophilic installation of carbon functional groups on the ...furan and thiophene nuclei with complete regioselectivity.
The treatment of the 5-(phenylsulfinyl)indoles with trifluoroacetic anhydride in the presence of carbon nucleophiles achieved the title reactions with complete regioselectivity.
The treatment of the ...5-(phenylsulfinyl)indoles with trifluoroacetic anhydride in the presence of carbon nucleophiles achieved the title reactions with complete regioselectivity.
Cardiac involvement of sarcoid lesions is diagnosed by myocardial biopsy which is frequently false-negative,and patients with cardiac sarcoidosis(CS) who have impaired left ventricular(LV) systolic ...function are sometimes diagnosed with dilated cardiomyopathy(DCM).Late gadolinium enhancement(LE) in magnetic resonance imaging is now a critical finding in diagnosing CS,and the novel Japanese guideline considers myocardial LE to be a major criterion of CS.This article describes the value of LE in patients with CS who have impaired LV systolic function,particularly the diagnostic and clinical significance of LE distribution in comparison with DCM.LE existed at all LV segments and myocardial layers in patients with CS,whereas it was localized predominantly in the midwall of basal to mid septum in those with DCM.Transmural(nodular),circumferential,and subepicardial and subendocardial LE distribution were highly specific in patients with CS,whereas the prevalence of striated midwall LE were high both in patients with CS and with DCM.Since sarcoidosis patients with LE have higher incidences of heart failure symptoms,ventricular tachyarrhythmia and sudden cardiac death,the analyses of extent and distribution of LE are crucial in early diagnosis and therapeutic approach for patients with CS.
Currently, no established biomarkers exist for presymptomatic sporadic Creutzfeldt-Jakob disease (sCJD). The purpose of this study was to raise awareness about sCJD cases showing abnormalities on ...brain MRI diffusion-weighted imaging (DWI) before symptom onset and demonstrate temporal changes in DWI abnormalities during the preclinical period.
We described the clinical presentation including the results of MRI-performed multiple times in the preclinical period-and the diagnostic workup of a middle-aged man with sCJD.
MRI of the brain performed 27 months before symptom onset revealed an extremely localized lesion on DWI in the right occipital cortex. Follow-up MRI scans showed propagation of DWI abnormalities along the cortices without the appearance of neurologic symptoms/signs. After symptom onset, the patient's neuropsychiatric condition rapidly deteriorated. Elevated total tau protein levels and positive 14-3-3 protein were observed in the CSF, and periodic synchronous discharges using electroencephalography resulted in the diagnosis of sCJD.
CJD should be considered in differential diagnoses when localized DWI signal abnormalities propagate along the cortices over time, even in the absence of typical CJD symptoms. DWI signal abnormalities on brain MRI scans may be highly sensitive diagnostic markers for CJD, even in the preclinical stage.
NISQ (Noisy, Intermediate-Scale Quantum) computing requires error mitigation to achieve meaningful computation. Our compilation tool development focuses on the fact that the error rates of individual ...qubits are not equal, with a goal of maximizing the success probability of real-world subroutines such as an adder circuit. We begin by establishing a metric for choosing among possible paths and circuit alternatives for executing gates between variables placed far apart within the processor, and test our approach on two IBM 20-qubit systems named Tokyo and Poughkeepsie. We find that a single-number metric describing the fidelity of individual gates is a useful but imperfect guide.
Our compiler uses this subsystem and maps complete circuits onto the machine using a beam search-based heuristic that will scale as processor and program sizes grow. To evaluate the whole compilation process, we compiled and executed adder circuits, then calculated the Kullback–Leibler divergence (KL-divergence, a measure of the distance between two probability distributions). For a circuit within the capabilities of the hardware, our compilation increases estimated success probability and reduces KL-divergence relative to an error-oblivious placement.
An anti-human interleukin 5 receptor (hIL-5R) humanized immunoglobulin G1 (IgG1) and an anti-CD20 chimeric IgG1 produced by
rat hybridoma YB2/0 cell lines showed more than 50-fold higher ...antibody-dependent cellular cytotoxicity (ADCC) using purified
human peripheral blood mononuclear cells as effector than those produced by Chinese hamster ovary (CHO) cell lines. Monosaccharide
composition and oligosaccharide profiling analysis showed that low fucose (Fuc) content of complex-type oligosaccharides was
characteristic in YB2/0-produced IgG1s compared with high Fuc content of CHO-produced IgG1s. YB2/0-produced anti-hIL-5R IgG1
was subjected to Lens culinaris aggulutin affinity column and fractionated based on the contents of Fuc. The lower Fuc IgG1 had higher ADCC than the IgG1
before separation. In contrast, the content of bisecting GlcNAc of the IgG1 affected ADCC much less than that of Fuc. In addition,
the correlation between Gal and ADCC was not observed. When the combined effect of Fuc and bisecting GlcNAc was examined in
anti-CD20 IgG1, only a severalfold increase of ADCC was observed by the addition of GlcNAc to highly fucosylated IgG1. Quantitative
PCR analysis indicated that YB2/0 cells had lower expression level of FUT8 mRNA, which codes α1,6-fucosyltransferase, than
CHO cells. Overexpression of FUT8 mRNA in YB2/0 cells led to an increase of fucosylated oligosaccharides and decrease of ADCC
of the IgG1. These results indicate that the lack of fucosylation of IgG1 has the most critical role in enhancement of ADCC,
although several reports have suggested the importance of Gal or bisecting GlcNAc and provide important information to produce
the effective therapeutic antibody.
Our study aimed to investigate both the clinical implications of late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) and the relation of LGE to clinical findings in patients ...with Takotsubo cardiomyopathy (TTC).
We evaluated 20 consecutive patients (2 men, 18 women; median age, 77 years; interquartile range IQR 67-82 years) who were admitted to our hospital with the diagnosis of TTC. CMR was performed within 1 week after admission, and follow-up studies were conducted 1.5 and 6 months later.
In 8 patients, CMR imaging during the sub-acute phase revealed LGE in the area matched with wall motion impairment. Cardiogenic shock was more frequently observed in patients with LGE than in those without LGE (38% vs 0%, p = 0.049). The patients with LGE needed a longer duration for ECG normalization and recovery of wall motion than did those without LGE (median 205 days, IQR 152-363 vs 68 days, 43-145, p = 0.005; 15 days, 10-185 vs 7 days, 4-13, p = 0.030, respectively). In 5 of these 8 patients, LGE disappeared within 45-180 days (170, IQR 56-180) of onset. The patients with LGE remaining in the chronic phase had higher peak creatine kinase levels than did those without LGE (median 307 IU/L, IQR 264-460 vs 202 IU/L, 120-218, p = 0.017).
LGE by CMR in the sub-acute phase may be associated with the severity and prolonged recovery to normal of clinical findings in TTC.
Background:Although previous studies have suggested a certain prevalence of Fabry disease (FD) in left ventricular hypertrophy (LVH) patients, the screening of FD is difficult because of its ...wide-ranging clinical phenotypes. We aimed to clarify the utility of combined measurement of plasma globotriaosylsphingosine (lyso-Gb3) concentration and α-galactosidase A activity (α-GAL) as a primary screening of FD in unexplained LVH patients.Methods and Results:Between 2014 and 2016, both lyso-Gb3 and α-GAL were measured in 277 consecutive patients (male 215, female 62, age 25–79 years) with left ventricular wall thickness >12 mm on echocardiogram: 5 patients (1.8%) screened positive (2 (0.7%) showed high lyso-Gb3 and 4 (1.4%) had low α-GAL levels). Finally, 2 patients (0.7%) were diagnosed with clinically significant FD. In 1 case, a female heterozygote with normal α-GAL levels had genetic variants of unknown significance and was diagnosed as FD by endomyocardial biopsy. The other case was a male chronic renal failure patient requiring hemodialysis, and he had a p.R112H mutation. In both cases there were high lyso-Gb3 levels.Conclusions:The serum lyso-Gb3 level can be relevant for clinically significant FD, and combined measurement of lyso-Gb3 and α-GAL can provide better screening of FD in unexplained LVH patients.
Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan
Submitted 26 April 2008
; accepted in final form 28 January 2009
Reactive oxygen ...species (ROS) production during ischemia-reperfusion (I/R) is thought to be a critical factor for myocardial injury. However, a small amount of ROS during the ischemic preconditioning (IPC) may provide a signal for cardioprotection. We have previously reported that the repetitive pretreatment of a small amount of ROS hydrogen peroxide (H 2 O 2 ), 2 µM mimicked the IPC-induced cardioprotection in the Langendorff-perfused rat hearts. We further investigated the mechanisms of the ROS-induced cardioprotection against I/R injury and tested the hypothesis whether it could mediate the mitochondrial permeability transition pore (mPTP) opening. The Langendorff-perfused rat hearts were subjected to 35 min ischemia and 40 min reperfusion, and the pretreatment of H 2 O 2 (2 µM) significantly improved the postischemic recoveries in left ventricular developed pressure, intracellular phosphocreatine, and ATP levels. A specific mPTP inhibitor cyclosporin A (CsA; 0.2 µM) canceled these H 2 O 2 -induced effects. In isolated permeabilized myocytes, H 2 O 2 (1 µM) accelerated the calcein leakage from mitochondria in a CsA-sensitive manner, indicating the opening of mPTP by H 2 O 2 . However, H 2 O 2 did not depolarize mitochondrial membrane potential ( m ) even in the presence of oligomycin (F 1 /F 0 ATPase inhibitor; 1 µM) and decreased mitochondrial Ca 2+ concentration (Ca 2+ m ) by accelerating the mitochondrial Ca 2+ extrusion via an mPTP. We conclude that the transient mPTP opening could be involved in the H 2 O 2 -induced cardioprotection against reperfusion injury, and the reduction of Ca 2+ m without the change in m might be a possible mechanism for the protection.
energy metabolism; nuclear magnetic resonance spectroscopy; permeabilized myocytes; mitochondrial calcium
Address for reprint requests and other correspondence: M. Saotome, Division of Cardiology, Internal Medicine III, Hamamatsu Univ. School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan (e-mail: msaotome{at}hama-med.ac.jp )
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