Factors Influencing Breast Density in Japanese Women Aged 40-49 in Breast Cancer Screening Mammography

A relatively large number of women in their 40s with high-density breasts, in which it can be difficult to detect lesions, are encountered in mammography cancer screenings in Japan. Here, we retrospectively investigated factors related to breast density. Two hundred women (40-49 years old) were examined at the screening center in our hospital. Multivariate analysis showed that factors such as small abdominal circumference, high HDL cholesterol, and no history of childbirth were related to high breast density in women in their 40s undergoing mammography. Other non-mammographic screening methods should be considered in women with abdominal circumferences ＜76cm, HDL-C >53mg/dl, and no history of childbirth, as there is a strong possibility of these women having high-density breasts that can make lesion detection difficult

Tyrphostin AG 1478 Accelerates Hydrogen Peroxide-Induced Apoptosis in A431 Cells

Oxidative stress is a potent inducer of apoptosis and activates protein tyrosine kinases and cytokine receptors, such as the epidermal growth factor receptor (EGFR). Previous studies suggest that cytokine receptors are potential effectors for anti-apoptotic signals, but it has not previously been determined whether cytokine receptors regulate down-stream protein kinases. To investigate the role of EGFR on oxidative stress-induced apoptosis and its downstream protein kinases, we blocked EGFR activation with Tyrphostin AG1478, a highly selective EGFR inhibitor. We determined that Tyrphostin AG1478 accelerated hydrogen peroxide-induced apoptosis in A431 cells, with activation of caspases 3 and 9, and decreased mitochondrial membrane potential. Hydrogen peroxide induced-activation of EGFR, Akt/PKB, MAPK, and Bad (both Ser-112 and Ser-136 residues) were inhibited by Tyrphostin AG1478. These results suggest that early upstream signaling events, such as EGFR activation, exert anti-apoptotic effects by regulating MAPK, Akt/PKB, and phosphorylation of Bad

Analysis of multiple compound–protein interactions reveals novel bioactive molecules

The authors use machine learning of compound-protein interactions to explore drug polypharmacology and to efficiently identify bioactive ligands, including novel scaffold-hopping compounds for two pharmaceutically important protein families: G-protein coupled receptors and protein kinases

Long-term efficacy of intravenously administered immunoglobulin in a case of polymyositis with limited application of steroid therapy.

A 72-year-old man who had been diagnosed with polymyositis (PM) was admitted to our hospital for pneumonia with exacerbation of muscle weakness, elevation of muscle enzymes, and positive magnetic resonance imaging findings. The patient had been refractory to cyclosporine A or azathioprine and hoped to avoid administration of high-dose steroids; IV immunoglobulin (IVIG) was therefore administered after improvement of the pneumonia. Two weeks after the IVIG therapy, muscle test scores, activities of daily living, and muscle enzymes were drastically improved. Twenty months after IVIG, no relapse of PM was observed

Immunolocalization of Adhesion Molecules in Rheumatoid and Osteoarthritic Synovial Tissues

To elucidate the potential role of adhesion molecules in the pathogenesis of rheumatoid arthritis (RA), we stained specimens of synovial tissue from patients with RA and osteoarthritis (OA) with monoclonal antibodies against adhesion molecules using an immunohistochemical method. Positive staining with anti-ICAM-1 monoclonal antibody was detected on the synovial lining cells, the sublining cells and the capillary endothelial cells in the synovium from patients with RA, and, to a lesser degree, in that from patients with OA. The capillary endothelial cells from patients with RA intensively expressed both ELAM-1 and VLA-5α molecules, in contrast to that from OA patients. The intensity of both ICAM-1 and ELAM-1 on the capillary endothelial cells in RA synovium was comparable to disease activity and to the degree of synovial proliferation. A high density of expression of LFA-1α , VLA-4α and VLA-5α was observed on the mononuclear cells that infiltrated the RA synovium, especially in the lesions with aggregated mononuclear cells. The findings clearly demonstrated an up-regulation of the expression of adhesion molecules on synovial cells, capillary endothelial cells and infiltrated mononuclear cells in the synovial tissues of patients with RA. This enhanced expression of adhesion molecules may play an important role in the migration of mononuclear cells into the synovial tissues and thus perpetuate the inflammatory response in these tissues

HER2 G776S mutation promotes oncogenic potential in colorectal cancer cells when accompanied by loss of APC function

Clinical cancer genome sequencing detects oncogenic variants that are potential targets for cancer treatment, but it also detects variants of unknown significance. These variants may interact with each other to influence tumor pathophysiology, however, such interactions have not been fully elucidated. Additionally, the effect of target therapy for those variants also unclarified. In this study, we investigated the biological functions of a HER2 mutation (G776S mutation) of unknown pathological significance, which was detected together with APC mutation by cancer genome sequencing of samples from a colorectal cancer (CRC) patient. Transfection of the HER2 G776S mutation alone slightly increased the kinase activity and phosphorylation of HER2 protein, but did not activate HER2 downstream signaling or alter the cell phenotype. On the other hand, the HER2 G776S mutation was shown to have strong oncogenic potential when loss of APC function was accompanied. We revealed that loss of APC function increased Wnt pathway activity but also increased RAS-GTP, which increased ERK phosphorylation triggered by HER2 G776S transfection. In addition, afatinib, a pan-HER tyrosine kinase inhibitor, suppressed tumor growth in xenografts derived from HER2 G776S-transfected CRC cells. These findings suggest that this HER2 mutation in CRC may be a potential therapeutic target

The role of IL-18 in the modulation of matrix metalloproteinases and migration of human natural killer (NK) cells

AbstractIn this study, we examined whether interleukin-18 (IL-18) affects natural killer (NK) cells' migration and matrix metalloproteinases (MMPs) production. We demonstrated that chemotaxis of human NK cells through basement membrane-like Matrigel was augmented by IL-18. As well, IL-18 stimulation induces the production of activated forms of matrix metalloproteinase-2 (MMP-2) as well as the production of pro-MMP-2 from NK cells. We also demonstrated that MT1-MMP expression on human NK cells, which is a major activator of MMP-2, was induced by IL-18 stimulation coordinated with MMP-2 activation. These data suggest that the MT1-MMP/MMP-2 system participates in the degradation of basement membrane components and thus contributes to NK cell migration

CD4+CD25(high)CD127(low/-) Treg cell frequency from peripheral blood correlates with disease activity in patients with rheumatoid arthritis.

To investigate whether the frequency of peripheral blood (PB) regulatory T cells (Treg) correlates with the clinical disease activity of rheumatoid arthritis (RA)

A single centre retrospective analysis of AECG classification criteria for primary Sjogren\u27s syndrome based on 112 minor salivary gland biopsies in a Japanese population.

OBJECTIVE: To assess the usefulness and performance of the American European Consensus Group (AECG) criteria based on minor salivary gland biopsy (MSGB) in Japanese patients with primary SS. METHODS: Among 208 MSGB cases, we retrospectively selected 112 subjects who satisfied the complete set of AECG classification criteria. Of the 112 subjects studied, 63 primary SS patients and 49 non-SS group subjects were classified according to the AECG criteria. The contribution of subjective and objective components was statistically analysed. RESULTS: Sex, dry eye, Saxon test, Schirmer\u27s test, anti-SSA/Ro antibody, MSGB grading and sialography statistically contributed to the diagnosis. Multiple logistic regression analysis showed that positive MSGB [odds ratio (OR) 105; 95% CI 13, 849), positive anti-SSA/Ro antibody (OR 96; 95% CI 10, 923), a positive Saxon test (OR 46; 95% CI, 6, 340) and the existence of dry eye (OR 8, 95% CI 2, 43) were associated with the diagnosis of primary SS. Among the components of the AECG criteria, MSGB and anti-SSA/Ro antibody were very strong contributors. Furthermore, the abnormal-finding positive rate in sialography significantly correlated with MSGB grading (P-value for trend = 0.0006), although other subjective and objective components were not associated with MSGB grading. CONCLUSION: The usefulness of the AECG criteria for Japanese primary SS patients was confirmed

Anti-centromere antibody-seropositive Sjögren's syndrome differs from conventional subgroup in clinical and pathological study

<p>Abstract</p> <p>Background</p> <p>To clarify the clinicopathological characteristics of primary Sjögren's syndrome (pSS) with anti-centromere antibody (ACA).</p> <p>Methods</p> <p>Characteristics of 14 patients of pSS with ACA were evaluated. All patients were anti-SS-A/Ro and SS-B/La antibodies negative (ACA+ group) without sclerodactyly. The prevalence of Raynaud's phenomenon (RP), titer of IgG and focus score (FS) in the minor salivary glands (MSGs) were determined. Quantification analysis of Azan Mallory staining was performed to detect collagenous fiber. Forty eight patients in whom ACA was absent were chosen as the conventional (ACA-) pSS group.</p> <p>Results</p> <p>Prevalence of ACA+ SS patients was 14 out of 129 (10.85%) pSS patients. RP was observed in 61.5% of the patients with ACA. The level of IgG in the ACA+ group was significantly lower than that of the ACA- group (p = 0.018). Statistical difference was also found in the FS of MSGs from the ACA+ group (1.4 ± 1.0) as compared with the ACA- group (2.3 ± 1.6) (p = 0.035). In contrast, the amount of fibrous tissue was much higher in the ACA+ group (65052.2 ± 14520.6 μm²versus 26251.3 ± 14249.8 μm²) (p = 1.3 × 10^-12).</p> <p>Conclusions</p> <p>Low cellular infiltration but with an increase in fibrous tissues may explain the clinical feature of a high prevalence of RP and normal IgG concentration in ACA+ pSS.</p