Low energy virtual monochromatic CT with deep learning image reconstruction to improve delineation of endoleaks.

AIM: This study aimed to investigate the utility of low-energy virtual monochromatic imaging (VMI) combined with deep-learning image reconstruction (DLIR) in improving the delineation of endoleaks (ELs) after endovascular aortic repair (EVAR) in contrast-enhanced dual-energy CT (DECT). METHODS: A total of 61 consecutive patients (mean age, 77 years; 46 men) after EVAR who underwent contrast-enhanced DECT were enrolled. Virtual monochromatic 40- and 70-keV images were reconstructed using DLIR (TrueFidelity-H) and conventional hybrid iterative reconstruction (IR). Contrast-to-noise ratio (CNR) of the EL on the venous-phase CT was calculated. Four different reconstructed image series (hybrid IR and DLIR at two energy levels, 40- and 70-keV) were displayed side-by-side and visually assessed for EL conspicuity on a 5-point comparative scale from 0 (best) to -4 (significantly inferior). Two experienced radiologists independently conducted a qualitative evaluation of the CT images. RESULTS: A total of 30 out of 61 patients presented with an EL. On both 40- and 70-keV images, the CNR of the EL was significantly higher in DLIR than in hybrid IR (40-keV, 14.5 ± 7.3 vs 8.6 ± 4.2, P<0.001; 70-keV, 8.7 ± 4.5 vs 5.5 ± 2.6, P<0.001). The comparative scale of EL conspicuity in the 40-keV DLIR images (Observer1, -0.2 ± 0.4; Observer2, 0.0 ± 0.0) was significantly higher than 40-keV hybrid IR (Observer1, -0.5 ± 0.5; Observer2, -1.0 ± 0.0; P<0.05), 70-keV DLIR (Observer1, -1.8 ± 0.4; Observer2, -2.0 ± 0.0; P<0.001) and 70-keV hybrid IR images (Observer1, -1.8 ± 0.4; Observer2, -2.4 ± 0.5; P<0.001), respectively. CONCLUSIONS: Using 40-keV VMI in combination with DLIR improves EL delineation after EVAR compared with the 70-keV VMI with hybrid IR or DLIR.

Combination of low-dose total skin electron beam therapy and subsequent localized skin electron beam therapy as a therapeutic option for advanced-stage mycosis fungoides.

Electron beam therapy (EBT) is an established treatment for mycosis fungoides (MF), but evidence for the use of EBT in advanced cutaneous conditions is limited, and optimal scheduling of the regimen for such conditions remains unclear. We report the case of a 44-year-old woman diagnosed with MF with widespread cutaneous lesions, including multiple huge tumours in the craniofacial area. Low-dose total skin (TS)EBT and subsequent localized skin (LS)EBT achieved striking improvements in eruptions. Oral etretinate was also administered during therapy. Our experience implies that combined TSEBT and LSEBT may be worth attempting when a patient presents with both widespread lesions and prominent tumours, even when the tumours are extremely large.

Acquired dermal melanocytosis of the face and extremities.

Acquired dermal melanocytosis (ADM) is a relatively rare, but well-described disease among adolescent to middle-aged East Asian women, particularly those of Japanese and Chinese descent. Clinically, ADM manifests as multiple punctate and greyish-brown pigmented areas 1-3 mm in diameter occurring on both sides of the forehead and zygomatic region. The subtype of ADM affecting the face and extremities is extremely rare even in East Asian women. We describe three patients with ADM of the face and extremities (ADMFE) and their characteristic clinical features. All patients were Japanese women, and showed multiple greyish-brown pigmentations on both nasal wings and on the extensor surface of the extremities. We found that the clinical features were strikingly uniform, and that a pigmented lesion on the nasal wing can be an important clue to distinguish ADMFE from other hyperpigmented diseases of the hands and feet. One patient was treated with Q-switched ruby laser with excellent outcome. Increased awareness of ADMFE can lead to earlier diagnosis and potential treatment.

Cascade Auger decays following Si KL23L23 Auger transitions in SiF4.

Cascade Si LVV Auger decays following KL(23)L(23) Auger transitions have been measured in SiF(4) molecule using an electron spectrometer combined with monochromatized undulator radiation. Molecular cascade processes from the two 2p holes states largely generate wide band structures in the spectra due to sequential electron emission leading to multiple valence holes. However, a peak with high yield is observed for the first time at about 103 eV, an energy being considerably higher than the energies of the normal LVV Auger electron, in the instance of the resonant excitation of Si 1s electron into the vacant molecular orbital. This peak is presumed to originate from the participator decay from the state with two 2p holes and one excited electron into the state with one 2p hole and one valence hole. A similar peak with less intensity is detected in the photoexcitation of the 1s electron into a Rydberg orbital. After the normal KL(23)L(23) Auger transition, the resultant cascade spectrum shows several peaks, e.g., 61 eV, 76 eV, and 82 eV. The former two peaks are assigned to the Auger transitions of Si atoms produced through molecular ion dissociation after cascade decays, and the latter is probably ascribed to the second step Auger decay into states having a 2p hole together with two valence holes.

Experimental observation of rotational Doppler broadening in a molecular system.

The first experimental evidence of rotational Doppler broadening in photoelectron spectra, reported here, show good agreement with recently described theoretical predictions. The dependence of the broadening on temperature and photoelectron kinetic energy is quantitatively predicted by the theory. The experiments verify that the rotational contributions to the linewidth are comparable to those from translational Doppler broadening and must be considered in the analysis of high-resolution photoelectron spectra. A classical model accounting for this newly observed effect is presented.

Electron-transfer-mediated decay and interatomic Coulombic decay from the triply ionized states in argon dimers.

We report the first observation of electron-transfer-mediated decay (ETMD) and interatomic Coulombic decay (ICD) from the triply charged states with an inner-valence vacancy, using the Ar dimer as an example. These ETMD and ICD processes, which lead to fragmentation of Ar(3+)-Ar into Ar(2+)-Ar(2+) and Ar(3+)-Ar+, respectively, are unambiguously identified by electron-ion-ion coincidence spectroscopy in which the kinetic energy of the ETMD or ICD electron and the kinetic energy release between the two fragment ions are measured in coincidence.

Three-electron interatomic Coulombic decay from the inner-valence double-vacancy states in NeAr.

We have unambiguously identified interatomic Coulombic decay in NeAr from the inner-valence double-vacancy state Ne-Ar(2+)(3s(-2)) to outer-valence triple-vacancy states Ne(+)(2p(-1))-Ar(2+)(3p(-2)) by momentum-resolved electron-ion multicoincidence. This is the first observation of interatomic Coulombic decay where three electrons (3e) participate. The results suggest that this 3e interatomic Coulombic decay is significantly faster than other competing processes like fluorescence decay and charge transfer via curve crossing.

Projection of Si 1s photoexcited orbitals into resonant Auger electron spectra in KLL decays of Si(CH3)4 and SiF4.

Spectator resonant KL(23)L(23) Auger electron spectra have been measured in the Si 1s photoexcitation region of Si(CH(3))(4) using monochromatized undulator radiation combined with a hemispherical electron spectrometer. The broad peak with high intensity in a total ion yield spectrum, coming mainly from excitation of a 1s electron into the 6t(2) vacant orbital, induces a spectator Auger decay in which the excited electron remains in its excited orbital. The component on the higher energy side of this peak through 1s excitation into a Rydberg orbital produces resonant Auger decays in which the excited Rydberg electron moves into a slightly higher Rydberg orbital, or is partly shaken up to a significantly higher Rydberg orbital. These findings of Si(CH(3))(4) indicate a clear contrast to those for SiF(4), in which the 1s excitation into a Rydberg orbital induces a shake-down phenomenon as well as a shake-up one. The results of these molecules exhibit a clear splitting effect among excited orbitals which are smeared out by overlapping due to lifetime widths and due to densely populated levels in the 1s electron excitation spectrum. This is consistent with the calculation on photoexcitation within the framework of density functional theory.

A Japanese-specific recurrent mutation and a novel splice site mutation in the LAMC2 gene identified in two Japanese families with Herlitz junctional epidermolysis bullosa.

BACKGROUND: Herlitz junctional epidermolysis bullosa (H-JEB) is an extremely rare genodermatosis characterized by lethality owing to severe blister formation. We report two unrelated Japanese patients with H-JEB. Genetic analyses detected a single nonsense mutation on the LAMC2 gene in these two patients. AIM: To identify the mutation involved and describe the first reported Japanese recurrent mutation in the LAMC2 gene. METHODS: Direct sequencing was performed of DNA from either peripheral blood or fetal cells in amniotic fluid. Reverse transcriptase PCR was used to confirm that an aberrant transcript resulted from the splice site mutation. A haplotype analysis was performed to define the origin of the recurrent mutation. RESULTS: Both patients had blisters and erosions on the trunk and limbs at birth, with nail dystrophy. Patient 1 died as a result of sepsis at 30 weeks of age, and patient 2 died as a result of disseminated intravascular coagulation at 20 weeks of age. Mutation analysis of the LAMC2 gene revealed that patient 1 was compound heterozygous for a nonsense mutation (p.Cys553X) and a novel splice site mutation (c.2868+1delG), and patient 2 was a homozygous for p.Cys553X. Prenatal diagnosis performed during a subsequent pregnancy in family 2 revealed that this second child was heterozygous for p.Cys553X, and was thus not affected. Haplotype analysis suggested that a p.Cys553X allele derived from the same origin had been independently inherited by these two unrelated families. CONCLUSIONS: p.Cys553X in the LAMC2 gene may be a Japanese-specific recurrent mutation as a result of a founder effect, and it may therefore be useful for initial screening in the mutation analysis of H-JEB.

Valence photoelectron spectroscopy of N2 and CO: recoil-induced rotational excitation, relative intensities, and atomic orbital composition of molecular orbitals.

Recoil-induced rotational excitation accompanying photoionization has been measured for the X, A, and B states of N(2)(+) and CO(+) over a range of photon energies from 60 to 900 eV. The mean recoil excitation increases linearly with the kinetic energy of the photoelectron, with slopes ranging from 0.73×10(-5) to 1.40×10(-5). These slopes are generally (but not completely) in accord with a simple model that treats the electrons as if they were emitted from isolated atoms. This treatment takes into account the atom from which the electron is emitted, the molecular-frame angular distribution of the electron, and the dependence of the photoelectron cross section on photon energy, on atomic identity, and on the type of atomic orbital from which the electron is ejected. These measurements thus provide a tool for investigating the atomic orbital composition of the molecular orbitals. Additional insight into this composition is obtained from the relative intensities of the various photolines in the spectrum and their variation with photon energy. Although there are some discrepancies between the predictions of the model and the observations, many of these can be understood qualitatively from a comparison of atomic and molecular wavefunctions. A quantum-mechanical treatment of recoil-induced excitation predicts an oscillatory variation with photon energy of the excitation. However, the predicted oscillations are small compared with the uncertainties in the data, and, as a result, the currently available results cannot provide confirmation of the quantum-mechanical theory.

Terahertz spectroscopy of native-conformation and thermally denatured bovine serum albumin (BSA).

Proteins are expected to exhibit collective vibrational modes at terahertz frequencies. We have developed a promising approach to measure these motions by using a membrane device to hold samples. Samples of bovine serum albumin (BSA) in native and thermally denatured conformations were measured using terahertz time-domain spectroscopy. Clear differences were observed in transmittance and phase between native-conformation BSA samples and thermally denatured BSA samples. Time-domain data shows that samples exhibited relative time shifts when compared with a standard. Results suggest that there were differences in dielectric responses in the BSA samples, and these are probably associated with molecular conformational changes in the membrane device.

Recurrent Spindle Cell Carcinoma Shows Features of Mesenchymal Stem Cells.

This study investigated a case of spindle cell carcinoma (SpCC) in tongue pathological lesions. The patient experienced a local recurrence and distant metastasis after surgical intervention. Although standard chemotherapy was administered, a granulomatous mass continued to develop. This aggressive growth led to survival of the tumor. Secondary debulking surgery was performed to improve the patient's quality of life at the request of the patient. Using a tissue sample derived from the secondary debulking surgery, we performed an analysis of the tumor's cell surface antigens, differentiation potential, metastatic ability, and inhibition potential by anticancer reagents. In vitro analysis revealed that the cell population grown under adherent culture conditions expressed the mesenchymal stem cell (MSC) markers CD73, CD90, and CD105. The cell line established from this SpCC contained colony-forming unit fibroblasts (CFU-Fs) and exhibited multipotent differentiation into several mesenchymal lineages, including bone, cartilage, and fat. The SpCC cells also displayed vigorous mobilization. These characteristics suggested that they had the differentiation potential of mesenchymal cells, especially MSCs, rather than that of epithelial cells. The surgical specimen analyzed in this study resisted the molecular target reagent cetuximab, which is an epidermal growth factor receptor inhibitor. This clinical insight revealed that chemotherapy-resistant SpCC cells have different characteristics compared to most other cancer cells, which are sensitive to cetuximab. Our cell death assay revealed that SpCC cell death was induced by the anticancer drug imatinib, which is known to inhibit protein tyrosine kinase activity of ABL, platelet-derived growth factor receptor α (PDGFRα), and KIT. Here, we report recurrent SpCC with characteristics of MSCs and potential for treatment with imatinib.

Overexpression of aurora kinase A in mouse mammary epithelium induces genetic instability preceding mammary tumor formation.

Aurora-A/STK15/BTAK, which encodes a centrosome-associated kinase, is amplified and overexpressed in multiple types of human tumors, including breast cancer. However, the causal relationship between overexpression of Aurora-A and tumorigenesis has not been fully established due to contradictory data obtained from different experimental systems. To investigate this, we generated a mouse strain that carries an MMTV-Aurora-A transgene. We showed that all the MMTV-Aurora-A mice displayed enhanced branch morphogenesis in the mammary gland and about 40% developed mammary tumors at 20 months of age. The tumor incidence was significantly increased in a p53(+/-) mutation background with about 70% MMTV-Aurora-A;p53(+/-) animals developed tumors at 18 months of age. Of note, overexpression of Aurora-A led to genetic instability, characterized by centrosome amplification, chromosome tetraploidization and premature sister chromatid segregation, at stages prior to tumor formation. Most notably, the severe chromosomal abnormality did not cause cell death owing to the activation of AKT pathway, including elevated levels of phosphorylated AKT and mammalian target of rapamycin, and nuclear accumulation of cyclin D1, which enabled continuous proliferation of the tetraploid cells. These data establish Aurora-A as an oncogene that causes malignant transformation through inducing genetic instability and activating oncogenic pathways such as AKT and its downstream signaling.

Tumor suppressor p53 is required to modulate BRCA1 expression.

Individuals carrying mutations in BRCA1 or p53 genes are predisposed to a variety of cancers, and both tumor suppressor genes have been implicated in DNA damage response pathways. We have analyzed a possible functional link between p53 and BRCA1 genes. Here we show that BRCA1 expression levels are down-regulated in response to p53 induction in cells that undergo either growth arrest, senescence, or apoptosis. Physiological stimuli, such as exposure to DNA-damaging agents, also result in negative regulation of BRCA1 levels in a p53-dependent manner prior to causing cell cycle arrest. Nuclear run-on experiments and luciferase reporter assays demonstrate that the changes in BRCA1 expression are mainly due to transcriptional repression induced by p53. In conclusion, the data show that BRCA1 expression levels are controlled by the presence and activity of wild-type p53 and suggest the existence of an intracellular p53/BRCA1 pathway in the response of cells to stress conditions.

Identification and properties of peptidylarginine deiminase from rabbit skeletal muscle.

Peptidylarginine deiminase, which catalyzes the deimination of arginyl residues in protein, was identified and partially purified from rabbit skeletal muscle. The specific activity of the crude extract from the muscle was aboutt 120 times that of the extract from newborn rat epidermis. The enzyme was purified abou 250-fold over the initial extract of rabbit skeletal muscle in a yield of about 53%. The enzyme requires Ca2+ as an essential cofactor and the activity was not inhibited by monoiodoacetate or PCMB. The molecular weight of the enzyme was found to be about 115,000 by gel chromatography on Bio-Gel P-300. The enzyme catalyzed the deimination of arginyl residue when both the alpha-amino and alpha-carboxyl groups were substituted, and showed low activity when substrates had either a free alpha-amino or a free alpha-carboxyl group. The action of the enzyme on free L-arginine was negligible. Proteins such as protamine, histone, and ribonuclease A were better substrates than the other small synthetic peptides tested.

Heterotopic pancreas of the esophagus associated with a rare type of esophageal atresia.

An infant with a rare type of esophageal/tracheal anomaly associated with heterotopic pancreas of the esophagus is herein reported. The upper pouch containing heterotopic pancreas reached 1.5 cm below the tracheal carina, and the distal esophagus connected to the trachea 2 cm above the tracheal carina and thus formed a partial duplication of the esophagus. Heterotopic pancreas of the esophagus is extremely rare, with only 7 cases previously reported. Here we report the combination of heterotopic pancreas and esophageal atresia with tracheoesophageal fistula.

Effect of dimerization of the D-glucose analogue of muramyl dipeptide on stimulation of macrophage-like cells.

N-Acetylmuramyl-L-alanyl-D-isoglutamine (MDP) is the minimum required structure responsible for the immunoadjuvant activity of the bacterial cell wall. The D-glucose analogue of MDP (GADP) was reported to show a higher immunoadjuvant activity than MDP itself. Although the mechanism of activation by MDP and the existence of receptor against MDP are not clear, the patch formation and cluster formation of receptors are important steps on the signal transduction by such bioactive molecules. It is expected that the cluster effect such as antennary oligosaccharides reported by Lee et al. increased the affinity of ligand against receptor and accelerated the patch formation and cluster formation of receptors. In order to discuss the effect of multivalent-ligand formation of GADP on the activation of immunocompetent cells in more detail, we have synthesized GADP dimers combined through various lengths of alkyl and poly(ethylene glycol) (PEG) spacer groups as the simple models of multivalent-ligand molecule of GADP and evaluated their immunological enhancement activities in vitro. The GADP dimers showed a higher level stimulatory activities against macrophage-like cells than free GADP and monomeric GADP derivatives.

Enlarged focal nodular hyperplasia of the liver under the influence of oral contraceptives.

Two cases of focal nodular hyperplasia of the liver in mature women treated with the oral contraceptive are described. Radiological investigations in one case revealed the typical findings of focal nodular hyperplasia with computed tomography and magnetic resonance imaging demonstrating central scar structures while spoke-wheel appearance was evident on arteriography, in the other case however findings were atypical. Routine investigations including liver function tests and alpha-fetoprotein levels were normal while hepatitis B surface antigen and hepatitis C virus antibody were negative. The lesions of these two cases enlarged significantly during the follow-up and they were therefore surgically resected. Pathological features of both resected specimens, such as hepatocellular hyperplasia, bile duct proliferation and vascular abnormalities, were compatible with focal nodular hyperplasia. It has been suggested that tumor growth may be augmented by sex hormone stimulation and therefore estrogen and progesterone receptor expressions in the resected tumors were determined by immunocytochemistry. Interestingly, stainings for both receptors were negative. In case 2, the tumor was enlarging although oral contraceptive use had been discontinued for the past 7 years. These results suggest that there is no direct relationship of focal nodular hyperplasia with oral contraceptives. The role of sex hormones in focal nodular hyperplasia of the liver merits further study.