Synthesis of All-Peptide-Based Rotaxane from a Proline-Containing Cyclic Peptide.

Rotaxane cross-linkers enhance the toughness of the resulting rotaxane cross-linked polymers through a stress dispersion effect, which is attributed to the mobility of the interlocked structure. To date, the compositional diversity of rotaxane cross-linkers has been limited, and the poor compatibility of these cross-linkers with peptides and proteins has made their use in such materials challenging. The synthesis of a rotaxane composed of peptides may result in a biodegradable cross-linker that is compatible with peptides and proteins, allowing the fortification of polypeptides and proteins and ultimately leading to the development of innovative materials that possess excellent mechanical properties and biodegradability. However, the chemical synthesis of all-peptide-based rotaxanes has remained elusive because of the absence of strong binding motifs in peptides, which prevents an axial peptide from penetrating a cyclic peptide. Here, we synthesized all-peptide-based rotaxanes using an active template method for proline-containing cyclic peptides. The results of molecular dynamics simulations suggested that cyclic peptides with an expansive inner cavity and carbonyl oxygens oriented toward the center are favorable for rotaxane synthesis. This rotaxane synthesis method is expected to accelerate the synthesis of peptides and proteins with mechanically interlocked structures, potentially leading to the development of peptide- and protein-based materials with unprecedented functionalities.

Raman Spectroscopic and DFT Study of COA-Cl and Its Analogues.

COA-Cl is a newly synthesized adenosine analogue that exhibits various physiological activities. Its angiogenic, neurotropic, and neuroprotective potencies make it promising for the development of medicines. In this study, we show Raman spectroscopic study of COA-Cl to elucidate molecular vibrations and related chemical properties. Density functional theory calculations were combined with the Raman spectroscopic data to understand the details of each vibrational mode. Comparative analysis with adenine, adenosine, and other nucleic acid analogues enabled identification of unique Raman peaks originating from the cyclobutane moiety and chloro group of COA-Cl. This study provides fundamental knowledge and crucial insights for further development of COA-Cl and related chemical species.

Solvation in nitration of benzene and the valence electronic structure of the Wheland intermediate.

Nitration of benzene is a representative aromatic substitution reaction related to the σ-complex (arenium ion or "Wheland" intermediate) concept. This reaction is typically carried out in a mixed acid solution to generate nitronium ions, and how solvent molecules play roles in the reaction has been of great interest. Here we will shed new light on the reaction, namely the electronic structure and the microscopic insights of the solvation, which have been rarely discussed so far. We studied this process using the reference interaction site model-self consistent field with constrained spatial electron density distribution (RISM-SCF-cSED) method, considering sulfuric acid or water molecules as a solvent. In this method, the electronic structure of the solute and the solvation structure are self-consistently determined based on quantum chemistry and statistical mechanics of molecular liquids. The solvation free energy surfaces in solution and solvation structures were verified. In the bond formation process of benzene and nitronium ions, the solvation structure by sulfuric acid molecules drastically changes and the solvation effect on the free energy is quite large. We revealed largely contributing resonance structures in the π-electron system of the σ-complex in gas and solution phases by analysing the valence electronic structures.

MRI imaging features of HIV-related central nervous system diseases: diagnosis by pattern recognition in daily practice.

With the advent of antiretroviral therapy (ART), the prognosis of people infected with human immunodeficiency virus (HIV) has improved, and the frequency of HIV-related central nervous system (CNS) diseases has decreased. Nevertheless, mortality from HIV-related CNS diseases, including those associated with ART (e.g., immune reconstitution inflammatory syndrome) remains significant. Magnetic resonance imaging (MRI) can improve the outlook for people with HIV through early diagnosis and prompt treatment. For example, HIV encephalopathy shows a diffuse bilateral pattern, whereas progressive multifocal leukoencephalopathy, HIV-related primary CNS lymphoma, and CNS toxoplasmosis show focal patterns on MRI. Among the other diseases caused by opportunistic infections, CNS cryptococcosis and CNS tuberculosis have extremely poor prognoses unless diagnosed early. Immune reconstitution inflammatory syndrome shows distinct MRI findings from the offending opportunistic infections. Although distinguishing between HIV-related CNS diseases based on imaging alone is difficult, in this review, we discuss how pattern recognition approaches can contribute to their early differentiation.

Kabirimine, a New Cyclic Imine from an Okinawan Dinoflagellate.

On our quest for new bioactive molecules from marine sources, two cyclic imines (1, 2) were isolated from a dinoflagellate extract, inhibiting the growth of the respiratory syncytial virus (RSV). Compound 1 was identified as a known molecule portimine, while 2 was elucidated to be a new cyclic imine, named kabirimine. The absolute stereochemistry of 1 was determined by crystallographic work and chiral derivatization, whereas the structure of 2 was elucidated by means of spectroscopic analysis and computational study on all the possible isomers. Compound 1 showed potent cytotoxicity (CC50 < 0.097 µM) against HEp2 cells, while 2 exhibited moderate antiviral activity against RSV with IC50 = 4.20 µM (95% CI 3.31-5.33).

Extrauterine Choriocarcinoma in the Fallopian Tube Following Infertility Treatment: Implications for the Management of Early-Detected Ectopic Pregnancies.

Extrauterine choriocarcinoma in the fallopian tube is very rare and is often diagnosed and treated as an ectopic tubal pregnancy. A 34-year-old woman who initially became pregnant after infertility treatment using ovulation induction with clomiphene citrate and intrauterine insemination was later diagnosed with an extrauterine choriocarcinoma in the left fallopian tube. Because of suspected left ectopic tubal pregnancy based on ultrasonography findings and a high level of ß-human chorionic gonadotropin (ß-hCG; 7054.3 mIU/mL), the patient underwent diagnostic laparoscopy at a gestational age of 6 weeks. Left salpingectomy was performed based on the operative diagnosis of an ectopic tubal pregnancy. No signs of tubal rupture or leakage of contents from the fallopian tube were observed during the operation. Her serum ß-hCG dropped to 10.3 mIU/mL at 15 days postoperatively. Histopathology demonstrated an extrauterine choriocarcinoma in the removed fallopian tube, and the patient was referred to a regional oncologic hospital to receive additional adjuvant chemotherapy. This case indicates that conservative treatment for ectopic pregnancy should be chosen carefully, and that histopathology diagnosis and appropriate ß-hCG monitoring following treatment are important not only to diagnose persistent ectopic pregnancy, but also to rule out the possibility of a tubal choriocarcinoma.

Radiologic-Pathologic Correlation of Primary and Secondary Cardiomyopathies: MR Imaging and Histopathologic Findings in Hearts from Autopsy and Transplantation.

Cardiac magnetic resonance (MR) imaging with late gadolinium enhancement (LGE) is used to detect and assess the myocardial damage seen with a variety of cardiomyopathies. Gadolinium-based contrast material accumulates in the expanded interstitial space of the myocardium. Areas with LGE correspond to replacement fibrosis, fibrofatty change, epithelioid granuloma, inflammatory cell infiltration, cardiomyocyte necrosis, and amyloid deposition-conditions that represent a focal increase in interstitial space. Areas without LGE correspond to interstitial or plexiform fibrosis, mildly degenerated cardiomyocytes, inflammatory cell infiltration, and diffuse amyloid deposition-conditions that represent diffuse increases in interstitial space. LGE MR imaging cannot depict these diffuse changes and does not enable quantitative evaluation of this increased interstitial space because on inversion-recovery MR images, the inversion time is adjusted to null the signal from normal-appearing or the least enhancing regions of the myocardium. Thus, the absence of LGE does not always indicate normal myocardial tissue. The use of current T1 mapping techniques enables one to overcome these drawbacks of LGE imaging, detect diffuse myocardial abnormalities, and perform quantitative analysis of the interstitial space. The authors describe the histopathologic and corresponding cardiac MR imaging findings of hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, cardiac sarcoidosis, giant cell myocarditis, and cardiac amyloidosis-mainly those seen on LGE MR images-as assessed by using whole-heart specimens obtained from autopsy or transplantation. ©RSNA, 2017.

Radiation-Dose-Lowering Effects of Landiolol Hydrochloride in Coronary Angiography Using Computed Tomography (DELIGHT)　- A Prospective Multicenter Study.

BACKGROUND: Controlling and decreasing the heart rate (HR) of patients during coronary computed tomography angiography (CCTA) is necessary to reduce radiation exposure and improve image quality. This prospective multicenter study aimed to investigate whether HR control with landiolol hydrochloride is useful for reducing radiation exposure during CCTA. METHODS AND RESULTS: We investigated 219 patients with suspected ischemic heart disease whose pretest HRs were 50-80 beats/min. We measured the HR before and after administration of landiolol hydrochloride and compared the estimated exposure inferred from the HR before administration of landiolol hydrochloride with the actual dose. After administration of landiolol hydrochloride, the mean HR (59.9±6.4 beats/min) at the time of CCTA was significantly lower than before administration (69.3±7.3 beats/min; P<0.001); 80% of the patients had controlled HRs at ≤65 beats/min. HR and blood pressure of all the patients recovered after the scan. The mean radiation dose in all patients was approximately 50% derived from the inferred dose before use of landiolol hydrochloride (4.5±3.2 vs. 9.0±3.7 mSv; P<0.001). There were no adverse events during this study. CONCLUSIONS: The use of landiolol hydrochloride during CCTA was safe and resulted in approximately 50% decrease in radiation exposure dose, suggesting the clinical usefulness of this drug. (Circ J 2016; 80: 1225-1231).

[Role of cardiac computed tomography in cardiac surgery].

In the field of cardiovascular surgery, cardiac computed tomography (CT) has served an important role in association with the improvement of the spatial and temporal resolution. Because CT angiography (CTA) provides more available information than plain CT, CTA has been increasingly used to access the coronary arteries and graft patency after coronary artery bypass grafting (CABG). Recently, minimally invasive cardiac surgeries, including CABG with left mini-thoracotomy and mitral valve surgery with right mini-thoracotomy, are revived, which requires preoperative CTA to make a strategy of incision placement on the basis of anatomical relationship between the target structure of the heart and the thorax. In Japan, transcatheter aortic valve implantation (TAVI) was approved in the late 2013, and is expected to be widely performed in the future. CTA is extremely useful for TAVI patients to determine the choice of the valve size and the surgical approach. CT provides many other valuable findings to us, but if we cannot fully leverage it in the daily cardiovascular surgery, its value is decreased. We have to acquire enough skill to maximize the performance of CT in the practical clinical setting.

Impact of diabetes mellitus on characteristics of carotid plaques and outcomes after carotid endarterectomy.

BACKGROUND: Published results for carotid endarterectomy (CEA) in symptomatic and asymptomatic severe carotid stenosis with diabetes mellitus (DM) are contradictory. To evaluate perioperative and long-term results of CEA in patients with DM, we retrospectively analyzed data of patients with or without DM who underwent CEA in our institute. METHODS: Between January 2005 and December 2010, 281 consecutive CEAs were performed in 268 patients under general anesthesia. All patients were subject to cardiac work-ups before surgery, and coronary revascularization was performed prior to CEA if patients were diagnosed with significant coronary artery stenosis. Lesion characteristics were assessed by a duplex ultrasound scan, computed tomography angiography (CTA), and plaque imaging on magnetic resonance imaging (MRI) before surgery, and patients were followed-up by a duplex ultrasound scan at three, six, and 12 months, then yearly, after surgery. RESULTS: Of 281 cases, 136 had DM (48 %). Diabetic patients more frequently had a history of coronary artery disease than non-diabetic patients (48.5 % vs. 36.6 %, P = 0.042). Coronary intervention prior to CEA was more frequently performed in diabetic patients than in non-diabetic patients (22.1 % vs. 11.0 %, P = 0.013). The incidence of perioperative (30 day) stroke (P = 1.000), death (P = 1.000), and cardiac complications (P = 0.484) did not differ among groups. Follow-up was available in 77.2 % of patients, with a median duration of 50 months (interquartile range, 32.1-67.2 months). The incidence of ipsilateral stroke (P = 0.720), death (P = 0.351), and severe restenosis (peak systolic velocity > 230 cm/sec) (P = 0.905) were not different between groups. CONCLUSIONS: DM does not increase the risk of perioperative complications and does not influence long-term outcomes after CEA if preexisting vascular risk factors and cardiac diseases are appropriately evaluated and treated before surgery.

Bone-destroying candida infection following left ventricular assist device explant.

Infections associated with left ventricular assist devices (LVADs) constitute an important clinical issue because they are difficult to completely eradicate without removal of the LVAD itself and can sometimes be fatal. We encountered a case of extracorporeal LVAD-related candida infection in a patient who was successfully weaned from LVAD support. Although the patient appeared to have recovered from the infection, the patient was readmitted to our institute due to a relapse of candida infection 9 months after LVAD removal. Although the patient did not demonstrate any systemic sign of infection on admission, computed tomography images clearly showed that the residual apical cuff of the LVAD inflow cannula, which was infected with Candida albicans during the initial admission, resulted in re-infection that involved the chest wall with destruction of the adjacent rib.

Pseudoaneurysm at the cannulation site of the ascending aorta arising 8 days postoperatively: report of a case.

A postoperative pseudoaneurysm is a rare complication that is difficult to diagnose. Computed tomography (CT) revealed a pseudoaneurysm in the ascending aorta of a 68-year-old female 8 days after mitral valve replacement and tricuspid annuloplasty. The defect was simply repaired during emergency surgery without cardiopulmonary bypass (CPB). The early detection of a postoperative pseudoaneurysm is important to avoid a second operation complicated by adhesions. Enhanced CT was useful for early detection in this patient. Pseudoaneurysm of the ascending aorta at the cannulation site can occur soon after surgery, and early recognition might allow simpler surgery without CPB.

Dynamic late gadolinium enhancement simply quantified using myocardium to lumen signal ratio: normal range of ratio and diffuse abnormal enhancement of cardiac amyloidosis.

PURPOSE: To detect abnormal myocardial tissue in patients with diffuse myocardial disease, we propose a simple technique of late gadolinium enhancement (LGE) using routine myocardial imaging modalities. MATERIALS AND METHODS: We retrospectively reviewed LGE images from 51 patients with normal myocardium and 10 patients with pathologically proven cardiac amyloidosis (CA). We obtained sequential LGE images from patients at 2, 5, 10, and 20 minutes after injection of Gd-DTPA (0.15 mmol/kg) with a fixed inversion time of 300 msec. We evaluated the signal intensity ratio of the myocardium to the left ventricular lumen (M/L) in one long and two short axial sections within 463 and 120 segments of normal myocardium and CA, respectively. Visually unenhanced and enhanced regions of myocardium were evaluated in each segment of patients with CA. RESULTS: Among normal myocardium, M/L (means ± standard deviation; SD) was stable with time (2, 5, 10, and 20 min: 0.34 ± 0.03, 0.31 ± 0.05, 0.34 ± 0.07, and 0.42 ± 0.11, respectively). The calculated M/L of unenhanced (0.60 ± 0.20, 0.68 ± 0.19, 0.76 ± 0.20, and 1.09 ± 0.25, respectively) and enhanced myocardium (0.77 ± 0.27, 0.99 ± 0.29, 1.20 ± 0.40, and 1.45 ± 0.54, respectively) in patients with CA was significantly greater than that seen for the normal myocardium at each time and increased over time. CONCLUSION: In patients with CA, diffuse myocardial abnormalities can be demonstrated using M/L, and this technique may be useful for the characterization of other myocardial diseases.

Assessment of calcified carotid plaque volume: comparison of contrast-enhanced dual-energy CT angiography and native single-energy CT.

OBJECTIVE: The purpose of this study was to compare estimates of calcified plaque volume in the carotid arteries based on contrast-enhanced dual-energy CT angiograms with volume estimates based on native CT scans. CONCLUSION: Detection of hard plaque in the carotid arteries with dual-energy CT angiography was successful in all patients. Estimates of calcified plaque volume based on dual-energy CT angiograms correlated well with those based on native single-energy CT scans but at a lower attenuation threshold (130 HU as opposed to 180 HU) were underestimates compared with those on the native CT scans.

DiaA dynamics are coupled with changes in initial origin complexes leading to helicase loading.

Chromosomal replication initiation requires the regulated formation of dynamic higher order complexes. Escherichia coli ATP-DnaA forms a specific multimer on oriC, resulting in DNA unwinding and DnaB helicase loading. DiaA, a DnaA-binding protein, directly stimulates the formation of ATP-DnaA multimers on oriC and ensures timely replication initiation. In this study, DnaA Phe-46 was identified as the crucial DiaA-binding site required for DiaA-stimulated ATP-DnaA assembly on oriC. Moreover, we show that DiaA stimulation requires only a subgroup of DnaA molecules binding to oriC, that DnaA Phe-46 is also important in the loading of DnaB helicase onto the oriC-DnaA complexes, and that this process also requires only a subgroup of DnaA molecules. Despite the use of only a DnaA subgroup, DiaA inhibited DnaB loading on oriC-DnaA complexes, suggesting that DiaA and DnaB bind to a common DnaA subgroup. A cellular factor can relieve the DiaA inhibition, allowing DnaB loading. Consistently, DnaA F46A caused retarded initiations in vivo in a DiaA-independent manner. It is therefore likely that DiaA dynamics are crucial in the regulated sequential progress of DnaA assembly and DnaB loading. We accordingly propose a model for dynamic structural changes of initial oriC complexes loading DiaA or DnaB helicase.

Angioplasty for non-arteriosclerotic renal artery stenosis: the efficacy of cutting balloon angioplasty versus conventional angioplasty.

PURPOSE: We examined the efficacy of conventional balloon angioplasty and cutting balloon angioplasty (CBA) for the treatment of non-arteriosclerotic renal artery stenosis (RAS). MATERIALS AND METHODS: From 1993 to 2005, 20 patients underwent 27 percutaneous transluminal renalangioplasty (PTRA) for non-arteriosclerotic RAS (men: 8, women: 12, 25.5 +/- 2 years old; 16 fibromuscular dysplasia (FMD), 4 Takayasu disease). We evaluated the efficacy of CBA by comparing the rate of initial technical success and surgical conversion. RESULTS: Before the clinical authorization of CBA, three of twelve patients (25 %) underwent surgical bypass due to the failure of PTRA due to the hardness of the lesion. After the approval of cutting balloon, we performed CBA in four cases (2 FMD,2 Takayasu disease) to dilate hard lesions, within which a properly sized balloon could not dilate due to their hardness, or to reduce the risk of local dissection. Initial successes were obtained in all patients (8/8, 100%) and none of the patients underwent surgical conversion. Despite of the good initial result, restenosis was observed in three cases within 6 month (3/4, 75%). Additional interventions were performed in all patients, then, the severity of the restenotic lesion was found not to be exceeded comparing with the initial lesion. CONCLUSION: The cutting balloon angioplasty may be safe and useful procedure for hard lesions of RAS caused by non-arteriosclerotic disease? especially fibromuscular dysplasia. The cutting balloon may provide the initial success, but the effect on long-term patency is still controversial.