Ultrasound screening of breast cancer

Ultrasound (US) screening of breast cancer was surveyed with the results of breast screening combined with mammography (MMG), US and clinical breast examination (CBE) at Ibaraki Health Service Association. Breast cancer is common among women in their late 40s in Japan, who tend to have small and dense breasts. Our results showed that US works as well as MMG in detecting breast cancers in women in their 40s, and both modalities are compensatory. There are many reports that the combination of MMG and US is a suitable method for breast screening in Japan. A large-scale randomized control trial is now ongoing to investigate whether breast screening by both MMG and US is useful to decrease breast cancer mortality.     

Safety of terminally gamma-ray-sterilized screws coated with fibroblast growth factor 2-calcium phosphate composite layers in non-human primates

Journal of Artificial Organs - Screws coated with fibroblast growth factor 2 (FGF-2)-calcium phosphate (CP) composite layers exhibit enhanced soft tissue and bone formation and angiogenesis because...     

Clinical predominance of whole-exome sequencing to evaluate microsatellite instability status

The microsatellite instability (MSI)/mismatch repair (MMR) status is one of the critical genomic biomarkers for predicting patient response to immune checkpoint inhibitors (ICIs). In this study, we aimed to investigate the concordance among the MSIsensor score obtained from whole-exome sequencing (WES), which could be a futuristic clinical cancer sequencing method, using only tumor tissues, MSI-PCR results, and immunohistochemistry (IHC) results to analyze various solid cancer types. We first endeavored to set the cut-off value of MSIsensor to determine functional deficient mismatch repair (f-dMMR) status. The MSI status of 1054 patients analyzed using WES was evaluated using MSIsensor. In addition, 87 of these patients were further analyzed using MSI-PCR and MMR IHC to calculate the sensitivity and specificity of the MSIsensor cut-off score. Our results showed that score 12.5 was an adequate cut-off score equivalent to PCR-confirmed MSS/MSI-low and MSI-high statuses, with sensitivity, specificity, and area under the curve values of 95.2%, 100%, and 0.998, respectively. Moreover, we identified false-positive cases of tumors with high mutational burden with an MSIsensor score <12.5, and optional IHC examination could rescue these cases. In conclusion, the MSIsensor score obtained using WES with tumor tissue showed a high clinical validity, with a cut-off value of 12.5 for f-dMMR detection, in combination with optional IHC analysis for MMR. Our novel algorithm will provide insights into the development of ICIs for cancer treatment, particularly when WES becomes a more common cancer genomic test in the near future.     

Preclinical pharmacology profile of CS-706, a novel cyclooxygenase-2 selective inhibitor, with potent antinociceptive and anti-inflammatory effects

We report here the preclinical anti-inflammatory profile of CS-706 [2-(4-ethoxyphenyl)-4-methyl-1-(4-sulfamoylphenyl)-1H-pyrrole], a novel cyclooxygenase-2 (COX-2) selective inhibitor. CS-706 selectively inhibited COX-2 in a human whole blood assay with an IC(50) of 0.31 microM, compared with an IC(50) of 2.2 microM for COX-1. The selectivity ratio of CS-706 was higher than those of the conventional non-steroidal anti-inflammatory drugs naproxen, indomethacin, and Diclofenac-Na, whereas it was lower than those of rofecoxib, valdecoxib and etoricoxib. It was similar to that of celecoxib. The pharmacokinetic profile of CS-706 showed rapid absorption and dose-proportional exposure after oral administration to rats. CS-706 inhibited prostaglandin E(2) production in inflamed tissue induced by yeast-injection in rats with potency similar to that of indomethacin. However, it inhibited gastric mucosal prostaglandin E(2) production in normal rats weakly compared with indomethacin. CS-706 ameliorated both yeast-induced inflammatory acute pain (ED(50)=0.0090 mg/kg) and adjuvant-induced chronic arthritic pain (ED(50)=0.30 mg/kg) in rats. CS-706 showed more potent antinociceptive activity than celecoxib and rofecoxib in these models. In an adjuvant-induced arthritic model in rats, CS-706 suppressed foot swelling prophylactically with an ID(50) of 0.10 mg/kg/day, and decreased foot swelling in the established arthritis therapeutically in a dose range of 0.040 to 1.0 mg/kg/day. Single administration of up to 100 mg/kg of CS-706 induced no significant gastric lesions in rats. In conclusion, CS-706 is a COX-2-selective inhibitor with a potent antinociceptive and anti-inflammatory activity and a gastric safety profile.     

Lectins modulate prostaglandin E2 production by rat peritoneal macrophages

The effect of Aloctin A (Alo A), a lectin having anti-inflammatory activities, on prostaglandin (PG) E₂ production by activated rat peritoneal macrophages was compared with that of concanavalin A (Con A), wheat germ agglutinin (WGA), plsum sativum agglutinin (PSA) and soybean agglutinin (SBA). Alo A, WGA, Con A and PSA at 10 g per ml inhibited PG E₂ production. But SBA, even at a dose of 1 g per ml, stimulated PG E₂ production. The inhibition by Alo A treatment of the release of radioactivity from (³H)arachidonic acid-labeled macrophages and the stimulation of this release by SBA treatment were observed. The uptake of (⁵¹Cr)-labeled sheep red blood cells by the macrophage was inhibited by Alo A, Con A, and PSA, all at 10 g per ml and SBA at 1 g per ml, however, WGA at 10 g per ml stimulated the uptake of the sheep red blood cells. The mechanism of the anti-inflammatory properties of Alo A was discussed.To whom correspondence should be addressed.     

Application of photogrammetry for analysis of occlusal contacts

IntroductionThe conventional 2D-analysis methods for occlusal contacts provided limited information on tooth morphology. This present study aims to detect 3D positional information of occlusal contacts from 2D-photos via photogrammetry. We propose an image processing solution for analysis of occlusal contacts and facets via the black silicone method and a photogrammetric technique.Materials and methodsThe occlusal facets were reconstructed from a 2D-photograph data-set of inter-occlusal records into a 3D image via photogrammetry. The configuration of the occlusal surface was reproduced with polygons. In addition, the textures of the occlusal contacts were mapped to each polygon.Difference from conventional methodsConstructing occlusal facets with 3D polygons from 2D-photos with photogrammetry was a defining characteristic of this image processing technique. It allowed us to better observe findings of the black silicone method. Compared with conventional 3D analysis using a 3D scanner, our 3D models did not reproduce the detail of the anatomical configuration. However, by merging the findings of the inter-occlusal record, the deformation of mandible and the displacement of periodontal ligaments under occlusal force were reflected in our model.Effect or performanceThrough the use of polygons in the conversion of 2D images to 3D images, we were able to define the relation between the location and direction of the occlusal contacts and facets, which was difficult to detect via conventional methods.ConclusionThrough our method of making a 3D polygon model, the findings of inter-occlusal records which reflected the jaw/teeth behavior under occlusal force could be observed 3-dimensionally.     

The usefulness of sebum check film for measuring the secretion of sebum

Patients with atopic dermatitis (AD) often present with dry skin, and the reduced secretion of sebum may be responsible for the impaired skin barrier function. A sebum check film enables the patient to self-evaluate the skin sebum content. This study compared the sebum check film with a sebumeter. The skin sebum content of the forehead was measured using a sebum check film and a sebumeter. The findings of the sebum content of healthy controls showed that the sebum dot fields on the sebum check film were significantly correlated with the sebum content measured using the sebumeter (r = 0.774, p < 0.001). In addition, the sebum fields on the sebum check film of AD patients (n = 26) were significantly less than those on the sebum check film of the controls (n = 30; p < 0.05). Furthermore, the analysis of the sebum fields on the sebum check film of the AD patients was significantly correlated with their sebum content findings that were obtained using a sebumeter (r = 0.592, p < 0.01). These findings indicate that the sebum check film is easy to use for measuring the sebum secretion and is suitable for self-checking the sebum contents by AD patients for daily skin care.     

Glycosphingolipid synthesis in cerebellar Purkinje neurons: Roles in myelin formation and axonal homeostasis

Glycosphingolipids (GSLs) occur in all mammalian plasma membranes. They are most abundant in neuronal cells and have essential roles in brain development. Glucosylceramide (GlcCer) synthase, which is encoded by the Ugcg gene, is the key enzyme driving the synthesis of most neuronal GSLs. Experiments using conditional Nestin‐Cre Ugcg knockout mice have shown that GSL synthesis in vivo is essential, especially for brain maturation. However, the roles of GSL synthesis in mature neurons remain elusive, since Nestin‐Cre is expressed in neural precursors as well as in postmitotic neurons. To address this problem, we generated Purkinje cell‐specific Ugcg knockout mice using mice that express Cre under the control of the L7 promoter. In these mice, Purkinje cells survived for at least 10–18 weeks after Ugcg deletion. We observed apparent axonal degeneration characterized by the accumulation of axonal transport cargos and aberrant membrane structures. Dendrites, however, were not affected. In addition, loss of GSLs disrupted myelin sheaths, which were characterized by detached paranodal loops. Notably, we observed doubly myelinated axons enveloped by an additional concentric myelin sheath around the original sheath. Our data show that axonal GlcCer‐based GSLs are essential for axonal homeostasis and correct myelin sheath formation. © 2010 Wiley‐Liss, Inc.