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Breast cancer is primarily classified into ductal and lobular types, as well as into noninvasive and invasive cancer. Invasive cancer involves lymphatic and hematogenous metastasis. In breast cancer patients with distant metastases, a neutrophil-derived serine protease; cathepsin G (Cat G), is highly expressed in breast cancer cells. Cat G induces cell migration and multicellular aggregation of MCF-7 human breast cancer cells; however, the mechanism is not clear. Recently, platelet-activating factor (PAF)-acetylhydrolase (PAF-AH), the enzyme responsible for PAF degradation, was reported to be overexpressed in some tumor types, including pancreatic and breast cancers. In this study, we investigated whether PAF-AH is involved in Cat G-induced aggregation and migration of MCF-7 cells. We first showed that Cat G increased PAF-AH activity and elevated PAFAH1B2 expression in MCF-7 cells. The elevated expression of PAFAH1B2 was also observed in human breast cancer tissue specimens by immunohistochemical analysis. Furthermore, knockdown of PAFAH1B2 in MCF-7 cells suppressed the cell migration and aggregation induced by low concentrations, but not high concentrations, of Cat G. Carbamoyl PAF (cPAF), a nonhydrolyzable PAF analog, completely suppressed Cat G-induced migration of MCF-7 cells. In addition, PAF receptor (PAFR) inhibition induced cell migration of MCF-7 cells even in the absence of Cat G, suggesting that Cat G suppresses the activation of PAFR through enhanced PAF degradation due to elevated expression of PAFAH1B2 and thereby induces malignant phenotypes in MCF-7 cells. Our findings may lead to a novel therapeutic modality for treating breast cancer by modulating the activity of Cat G/PAF signaling., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Tumor-associated macrophages are associated with more malignant phenotypes of esophageal squamous cell carcinoma (ESCC) cells. Previously, an indirect co-culture assay of ESCC cells and macrophages was used to identify several factors associated with ESCC progression. Herein, a direct co-culture assay of ESCC cells and macrophages was established, which more closely simulated the actual cancer microenvironment. Direct co-cultured ESCC cells had significantly increased migration and invasion abilities, and phosphorylation levels of Akt and p38 mitogen-activated protein kinase (MAPK) compared with monocultured ESCC cells. According to a cDNA microarray analysis between monocultured and co-cultured ESCC cells, both the expression and release of S100 calcium binding protein A8 and A9 (S100A8 and S100A9), which commonly exist and function as a heterodimer (herein, S100A8/A9), were significantly enhanced in co-cultured ESCC cells. The addition of recombinant human S100A8/A9 protein induced migration and invasion of ESCC cells via Akt and p38 MAPK signaling. Both S100A8 and S100A9 silencing suppressed migration, invasion, and phosphorylation of Akt and p38 MAPK in co-cultured ESCC cells. Moreover, ESCC patients with high S100A8/A9 expression exhibited significantly shorter disease-free survival (P = 0.005) and cause-specific survival (P = 0.038). These results suggest that S100A8/A9 expression and release in ESCC cells are enhanced by direct co-culture with macrophages and that S100A8/A9 promotes ESCC progression via Akt and p38 MAPK signaling pathways., (Copyright © 2022 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Tumor-associated macrophages (TAMs) promote tumor progression. The number of infiltrating TAMs is associated with poor prognosis in esophageal squamous cell carcinoma (ESCC) patients; however, the mechanism underlying this phenomenon is unclear. cDNA microarray analysis indicates that the expression of chemokine (C-C motif) ligand 1 (CCL1) is up-regulated in peripheral blood monocyte-derived macrophages stimulated using conditioned media from ESCC cells (TAM-like macrophages). Here, we evaluated the role of CCL1 in ESCC progression. CCL1 was overexpressed in TAM-like macrophages, and CCR8, a CCL1 receptor, was expressed on ESCC cell surface. TAM-like macrophages significantly enhanced the motility of ESCC cells, and neutralizing antibodies against CCL1 or CCR8 suppressed this increased motility. Recombinant human CCL1 promoted ESCC cell motility via the Akt/proline-rich Akt substrate of 40 kDa/mammalian target of rapamycin pathway. Phosphatidylinositol 3-kinase or Akt inhibitors, CCR8 silencing, and neutralizing antibody against CCR8 could significantly suppress these effects. The overexpression of CCL1 in stromal cells or CCR8 in ESCC cells was significantly associated with poor overall survival (P = 0.002 or P = 0.009, respectively) and disease-free survival (P = 0.009 or P = 0.047, respectively) in patients with ESCC. These results indicate that the interaction between stromal CCL1 and CCR8 on cancer cells promotes ESCC progression via the Akt/proline-rich Akt substrate of 40 kDa/mammalian target of rapamycin pathway, thereby providing novel therapeutic targets., (Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Two new alkaloidal metabolites, cordytakaoamides A (1) and B (2), as well as, 2-[(2-hydroxyethyl) amino] benzoic acid (3) and 2E-decenamide (4), and three known compounds (5-7) were isolated from ethyl acetate and n-butanol soluble portions of the entomopathogenic fungus, Cordyceps takaomontana NBRC 101754. Compounds 3 and 4 were isolated here for first time from natural resources. The chemical structures were established depending upon spectroscopic techniques such as 1D, 2D NMR, and HRMS. The absolute configuration of 1 and 2 was elucidated via the total synthesis of 1 as well as the experimental circular dichroism. Compound 3 was confirmed by a signal crystal X-ray analysis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The diagnosis of prosthetic valve endocarditis may be challenging in patients with an atypical clinical presentation. Virtually all infections associated with mechanical prosthetic valves are localized to the prosthesis-tissue junction at the sewing ring and are accompanied by tissue destruction around the prosthesis. Because the orifice of the mechanical prosthetic valve is made of metal and pyrolytic carbon, which do not enable the adherence of microorganisms, any vegetation originating from the interior of the valve orifice is usually rare. Here we present a rare case of pannus-induced mechanical prosthetic valve endocarditis that was difficult to diagnose., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Among cardiac calcified amorphous tumors, the mitral annular calcification-related calcified amorphous tumor is extremely rare. We herein describe 3 surgical cases of swinging calcified amorphous tumor with related mitral annular calcification. The clinical, echocardiographic, and pathophysiologic features are reported here together with a brief review of the literature., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Past nuclear disasters, such as the atomic bombings in 1945 and major accidents at nuclear power plants, have highlighted similarities in potential public health effects of radiation in both circumstances, including health issues unrelated to radiation exposure. Although the rarity of nuclear disasters limits opportunities to undertake rigorous research of evidence-based interventions and strategies, identification of lessons learned and development of an effective plan to protect the public, minimise negative effects, and protect emergency workers from exposure to high-dose radiation is important. Additionally, research is needed to help decision makers to avoid premature deaths among patients already in hospitals and other vulnerable groups during evacuation. Since nuclear disasters can affect hundreds of thousands of people, a substantial number of people are at risk of physical and mental harm in each disaster. During the recovery period after a nuclear disaster, physicians might need to screen for psychological burdens and provide general physical and mental health care for many affected residents who might experience long-term displacement. Reliable communication of personalised risks has emerged as a challenge for health-care professionals beyond the need to explain radiation protection. To overcome difficulties of risk communication and provide decision aids to protect workers, vulnerable people, and residents after a nuclear disaster, physicians should receive training in nuclear disaster response. This training should include evidence-based interventions, support decisions to balance potential harms and benefits, and take account of scientific uncertainty in provision of community health care. An open and joint learning process is essential to prepare for, and minimise the effects of, future nuclear disasters., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

437 nuclear power plants are in operation at present around the world to meet increasing energy demands. Unfortunately, five major nuclear accidents have occurred in the past--ie, at Kyshtym (Russia [then USSR], 1957), Windscale Piles (UK, 1957), Three Mile Island (USA, 1979), Chernobyl (Ukraine [then USSR], 1986), and Fukushima (Japan, 2011). The effects of these accidents on individuals and societies are diverse and enduring. Accumulated evidence about radiation health effects on atomic bomb survivors and other radiation-exposed people has formed the basis for national and international regulations about radiation protection. However, past experiences suggest that common issues were not necessarily physical health problems directly attributable to radiation exposure, but rather psychological and social effects. Additionally, evacuation and long-term displacement created severe health-care problems for the most vulnerable people, such as hospital inpatients and elderly people., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Acute exacerbation (AE) is a major cause of death in idiopathic pulmonary fibrosis (IPF). However, little is known about sensitive biomarkers for predicting AE. The aim of our study was to investigate the significance of KL-6 and CC-Chemokine Ligand 18 (CCL18) as predictors for AE of IPF., Methods: We prospectively collected a total of 77 patients with IPF. Serum levels of KL-6 and CCL18 were measured by ELISA. The correlation between baseline serum levels of the markers and the incidence of AE was evaluated., Results: Thirteen (17%) patients experienced AE during follow-up. Baseline serum KL-6 levels were significantly higher in patients who developed AE than in patients with stable IPF (p < 0.0001), whereas serum CCL18 levels showed no difference between these groups (p = 0.13). At a cut-off level of 1300 U/mL for KL-6, the sensitivity, specificity, accuracy and likelihood ratio to predict AE were 92%, 61%, 66% and 2.36, respectively. In the Kaplan-Meier analysis, patients with baseline serum KL-6 level ≥1300 U/mL experienced earlier onset of AE (p = 0.002), whereas CCL18 showed no predictive value (p = 0.11). In the multivariate analysis, baseline serum KL-6 (both continuous and at a cut-off level of ≥1300 U/mL) was an independent predictive factor for AE after adjustment for age, sex, smoking history and %vital capacity (hazard ratio = 1.001, 18.8; p = 0.010, 0.008, respectively)., Conclusions: Baseline serum KL-6 level is a sensitive predictor for the onset of AE in IPF., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Infection of a vascular prosthesis after a bypass surgery is relatively rare. However, once developed, serious complications can occur, such as bleeding, sepsis, and organ ischemia, occasionally resulting in leg amputation or even death in some cases. The treatment of a vascular prosthesis infection involves the necessary removal of the infected graft; subsequently, an extra-anatomical bypass surgery is often considered. We herein report a case in which postoperative methicillin-resistant Staphylococcus aureus infection caused dehiscence of the femoral vessels and exposure of the graft vessel and anastomosed area. The infected tissue was surgically removed (debridement), and the patient's condition was successfully treated by the application of a nonadherent dressing and vacuum-assisted closure therapy combined with the bridging technique., (Copyright © 2013. Published by Elsevier B.V.)

The growth of thyroid cells is tightly regulated by thyroid stimulating hormone (TSH) through the cyclic adenosine 3', 5'-monophosphate (cAMP) signaling pathway by potentiating the mitogenic activity of insulin and insulin-like growth factors (IGFs). However, we recently reported that thyroglobulin (Tg), a major product of the thyroid, also induces the growth of thyroid cells cultured in 0.2% serum in the absence of TSH and insulin. In this report, we demonstrate that Tg induced phosphorylation of molecules of the c-Raf/MEK/ERK pathway of the mitogen-activated protein kinase (MAPK). The MEK-1/2 inhibitor PD98059 suppressed Tg-induced phosphorylation of ERK1/2 and reduced bromodeoxyuridine (BrdU) incorporation. Tg also induced expression of the essential transcriptional factors c-Myc, c-Fos and c-Jun and phosphorylation of the retinoblastoma (Rb) protein. The present results, together with the previous report, suggest that Tg utilizes multiple signaling cascades to induce thyroid cell growth independent of TSH/cAMP stimulation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The stratum corneum (SC) plays an important role in cutaneous barrier function. Recent clarification of the pathophysiology of several keratoses has suggested that adhesive molecules contribute not only to SC construction but also to SC barrier function., Objective: The purpose of this study is to clarify how the distribution of adhesion molecules on corneocytes contributes to the construction of the SC and the overall organization and function of the cutaneous barrier., Methods: To investigate the distribution of desmoglein 1 (Dsg1), which may be a main component of corneodesmosomes (CDSs) in the SC, we used a bidimensional observation method using tape-stripped corneocytes and several immunohistochemical techniques to demonstrate the distribution of Dsg1 and to deduce internal events in the SC., Results: Immunofluorescence labeling showed that Dsg1 distributed on corneocytes of the outermost SC with a characteristic pattern at the periphery, or over the entire surface, and differences in this distribution pattern correlated with the transepidermal water loss (TEWL). Furthermore, electron microscopic analysis showed that (1) Dsg1 was localized on CDSs involved in adhesion, and (2) CDSs on the periphery of corneocytes contributed to the generation of the characteristic basket-weave structure., Conclusion: We explored the distribution pattern of Dsg1 in the SC via a non-invasive investigation tool. Our findings indicate the significance of adhesion molecules in the formation and function of the SC, and suggest that adhesion molecules are one of the important elements in barrier formation in addition to corneocytes, which act as bricks, and intercellular lipids, which act as mortar., (2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Thyroglobulin (Tg) is an essential substrate for thyroid hormone biosynthesis whose production is primarily limited to the thyroid follicular cell. We have previously identified an approximately 1.2 kb fragment of Tg mRNA in cultured mouse mesangial cells, and in the present study provide evidence showing that this transcript is transcribed and translated into a unique protein (kTg) in the kidney, but not the thyroid gland. Cloning of kTg from a mouse kidney cDNA library showed that transcription starts in the middle of intron 41 of the Tg gene and continues in-frame with the remaining coding sequence of thyroid-derived Tg beginning with exon 42. Translation of this mRNA is predicted to yield a protein of 367 amino acids (40 kDa) containing a unique 13 amino acid sequence serving as a signal peptide followed by a 354 amino acid segment identical to the carboxy-terminal end of thyroid Tg. Western blot analysis with an antibody directed against the C-terminus of thyroid Tg detected a 40 kDa protein expressed in the kidney. Immunohistochemistry with this antibody showed that immunoreactive Tg was localized in podocytes and the mesangial area of the renal glomerulus. A part of a homologous transcript was also detected in human kidney, and the kTg protein was recognized by sera from Hashimoto's thyroiditis but not from controls. Together these results suggest that a unique low molecular weight variant of Tg is expressed in the kidney, where it could serve both physiological and pathological roles, including that of an autoantigen.

Background: Posterior autologous pericardial annuloplasty is an option in mitral valve repair. However, the durability of posterior pericardial annuloplasty remains controversial., Methods: From June 1999 to July 2004, 49 patients (18 male and 31 female; mean age, 64 +/- 12 years) with isolated posterior leaflet prolapse received posterior autologous pericardial annuloplasty. Transthoracic echocardiographic examination before the operation, at the time of discharge, and then annually was performed and analyzed., Results: There was no incidence of in-hospital or late death. Only 1 patient (2.1%) required reoperation. In terms of recurrent mitral regurgitation, 31 patients (64.6%) exhibited grade 0 mitral regurgitation, 7 patients (14.6%) exhibited grade 1, and 9 patients (18.8%) exhibited grade 2, whereas only 1 patient (2.0%) exhibited more than grade 3. In terms of predicting postoperative recurrence of significant mitral regurgitation (> or =grade 2), multivariate Cox analysis demonstrated that marked left atrial dilatation and high fractional shortening were independent risk factors. In 8 of 10 patients significant mitral regurgitation recurred after discharge. In terms of left atrial dimension, no significant reduction was observed in the postdischarge recurrent group, and there was a significant difference of left atrial dimension between the postdischarge recurrent group and the nonrecurrent group at the time of discharge., Conclusions: The merits of mitral valve repair using posterior autologous pericardial annuloplasty are attractive. However, its use should be limited in selected patients with isolated posterior leaflet disease, nonenlarged atria, and non-high fractional shortening to maintain the durability of the mitral valve repair.

We examined the effect of alcohol ingestion on rat hepatocarcinogenesis induced by oral administration of synthetic female hormones, 0.075 mg of ethynylestradiol (EE) and 6.0 mg of norethindrone acetate (NA), everyday for 12 months to Wistar rats. Concomitant administration of 10% ethanol in drinking water resulted in the development of hepatocellular carcinoma (HCC) in 40.8% in female rats and 11.8% in male rats at 12 months, although the incidences of HCC following hormones administration alone were 8.0% in female rats and 0% in male rats. The incidence and the number of hyperplastic nodules in rats with concomitant alcohol treatment were significantly higher than that in rats with hormone treatment alone. The additional alcohol administration significantly increased the values of nuclear and cytosol estrogen receptors at 4 months. Synthetic female hormones and/or alcohol treatment also significantly increased the value of cytosol progesterone receptor at 4 months. 32P-postlabeling analysis of liver DNA revealed that alcohol enhanced the DNA adduct formation induced by hormones. Consequently, alcohol may affect rat hepatocarcinogenesis caused by synthetic female hormones in enhancing cell-proliferating activity via estrogen and progesterone receptors, and DNA adduct formation induced by synthetic female hormones.

Radionuclide ventriculographic studies were performed at rest and during exercise in 15 middle-aged asymptomatic patients with non-insulin-dependent diabetes mellitus (NIDDM) whose mean age was 58.7 +/- 10.5 years (mean +/- SD), and in 10 age- and sex-matched normal control subjects. The patients had neither clinical evidence of cardiovascular diseases nor obvious perfusion defects during maximal exercise testing with thallium-201 myocardial scintigraphy. The average left ventricular ejection fraction (LVEF) at rest was 69.1 +/- 5.3% in the diabetic patients and 65.6 +/- 4.2% in the control subjects, and during exercise, the average LVEFs were 68.3 +/- 6.9% and 72.1 +/- 5.0%, respectively. The changes in LVEF during exercise were -0.7 +/- 7.6% in the diabetic group and +6.5 +/- 2.6% in the control group (p < 0.01). However, the filling fraction during the first third of diastole at rest was significantly less in the diabetic group than in the control group (p < 0.05), the time to peak filling rate (TPF) was longer, and the TPF/R-R, normalized by the R-R interval and expressed as a percentage, was greater in the NIDDM patients than in the control subjects. There was close correlation between the abnormal response of LVEF to exercise and the reduced early diastolic filling in the diabetic patients. We concluded that 1) not only the response of LVEF to exercise but also the early left ventricular diastolic filling at rest are impaired in middle-aged asymptomatic NIDDM patients, and 2) some common factors could cause dysfunction of both the systolic and diastolic left ventricles in NIDDM patients, possibly latent global myocardial ischemia or metabolic myocardial disturbances.

A method for the quantitative determination of ammonium in human urine by high-performance liquid chromatography (HPLC) is described. After making fluorescent substances with fluorescamine, they were separated and quantified by their fluorometric intensity. The intensity (as measured by peak height) was linear between 0.5 and 5.0 micrograms, and coefficients of variation for elution time and peak height on replicate analysis of the standard were 0.15 and 4.2%, respectively. Recoveries of added ammonium were 96.5 and 97.3%, respectively, on 2.0 and 3.0 micrograms by this method. Detection limit of this method was 0.2 microgram. There was good agreement between the proposed HPLC method (X) and ion chromatographic method (Y), giving the relationships as Y = 0.956X + 0.012, r = 0.991.

Glucose stimulation of [32P]-prelabelled pancreatic islets induced an increased incorporation of radioactivity into phosphatidylinositol. Glucagon and agents that increases cAMP in the islet did not affect phosphatidylinositol turnover, in spite of increased release of insulin. Furthermore, the potent inhibitor of insulin release, somatostatin did not alter phospholipid metabolism. Colchicine inhibited glucose-stimulated turnover of phosphatidylinositol as well as insulin release. These results may suggest that: (1) cAMP and phosphatidylinositol turnover are involved in different transmembrane control system for regulating insulin release; and (2) the function of microtubules modulate phospholipid metabolism.