Comparative Study of Hepatocyte Growth Factor/Scatter Factor and Keratinocyte Growth Factor Effects on Human Keratinocytes

Hepatocyte growth factor/scatter factor (HGF/SF) and keratinocyte growth factor (KGF, also designated FGF-7) are paracrine growth factors secreted by mesenchymal cells and active on a variety of epithelial cell types. In this study, the biologic response of keratinocytes to these paracrine growth factors were compared. Stimulation of mitogenesis, migration, plasminogen activator (PA) activity, and fibronectin production were examined using human foreskin keratinocytes cultured in serum-free MCDB 153 medium. Although the two factors stimulated a similar level of proliferation when cells were maintained for 5 d in 1.8 mM Ca++, the peak effect of KGF, observed at 10 ng/ml, was approximately threefold higher than that of HGF/SF when cells were in medium containing 0.15 mM Ca++. Both agents promoted the migration of cells in low-calcium medium (0.08 mM Ca++). However, the magnitude of the response was approximately twofold greater for HGF/SF at 10 ng/ml than KGF at the same concentration. None of the matrix proteins such as type I collagen, type IV collagen, laminin, or fibronectin either stimulated or supressed HGF/SF-or KGF-stimulated kerationocyte migration. Both factors stimulated PA activity was maximal with the addition of 10 ng/ml of either factor. Neither factor increased the production of fibronectin under conditions in which transforming growth factor-β1 was active. These results indicate that HGF/SF and KGF, both recognized as paracrine growth factors, elicit distinctive patterns of response by keratinocytes, implying that they have different roles in epidermal physiology

Ultraviolet B irradiation increases endothelin-1 and endothelin receptor expression in cultured human keratinocytes

AbstractThe effect of ultraviolet B (UVB) irradiation on endothelin-1 (ET-1) and ET receptor expression was examined using cultured normal human keratinocytes. Keratinocytes secreted ET-1 in the medium at a level of 2.1 pg/day/105 cells. UVB irradiation up to 10 mJ/cm2 increased ET-1 secretion 3-fold, and potentiated expression of mRNA for ET-1. Both ETA and ETB receptor mRNAs were detected in keratinocytes, and their expression was up-regulated by 5 mJ/cm2 UVB irradiation

Electron identification using the TOPAZ detector at TRISTAN

We present an electron-identification method using the time-projection chamber and the lead-glass calorimeter in the TOPAZ detector system. Using this method we have achieved good electron identification against hadron backgrounds over a wide momentum range in the hadronic events produced by both single-photon exchange and two-photon processes. Pion-rejection factors and electron efficiencies were 163 and 68.4\% for high-$P_T$ electrons and 137 and 42.7\% for low-$P_T$ electrons in the single-photon-exchange process, and 8600 and 36.0\% for the two-photon process, respectively.Comment: 32 pages, latex format (article), 24 figures, submitted for publication

Protocol for a single-arm confirmatory trial of adjuvant chemoradiation for patients with high-risk rectal submucosal invasive cancer after local resection: Japan Clinical Oncology Group Study JCOG1612 (RESCUE study)

Introduction: Intestinal resection with lymph node dissection is the current standard treatment for high-risk lower rectal submucosal invasive cancer after local resection; however, surgery affects patients’ quality of life due to stoma placement or impaired anal sphincter function. A recent study demonstrated that adjuvant chemoradiation yields promising results. Methods and analysis: This study aims to confirm the non-inferiority of adjuvant chemoradiation, consisting of capecitabine and concurrent radiotherapy (45 Gy in 25 fractions), measured by 5-year relapse-free survival (RFS), over standard surgery in patients with high-risk lower rectal submucosal invasive cancer after local resection. The primary endpoint is 5 year RFS. The secondary endpoints are 10 years RFS, 5-year and 10-year overall survival, 5-year and 10-year local RFS, 5-year and 10-year proportion of anus-preservation without stoma, Wexner score, low anterior resection syndrome score, adverse events and serious adverse events. During the 5-year trial period, 210 patients will be accrued from 65 Japanese institutions. Ethics and dissemination: The National Cancer Center Hospital East Certified Review Board approved this study protocol in October 2018. The study is conducted in accordance with the precepts established in the Declaration of Helsinki and Clinical Trials Act. Written informed consent will be obtained from all eligible patients prior to registration. The primary results of this study will be published in an English article. In addition, the main results will be published on the websites of Japan Clinical Oncology Group (www.jcog.jp) and jRCT (https://jrct.niph.go.jp/). As to data curation, it has not been prepared yet. Trial registration number: jRCT103118007

Temperature and Density in the Foot Points of the Molecular Loops in the Galactic Center; Analysis of Multi-J Transitions of 12CO(J=1-0, 3-2, 4-3, 7-6), 13CO(J=1-0) and C18O(J=1-0)

Fukui et al. (2006) discovered two molecular loops in the Galactic center and argued that the foot points of the molecular loops, two bright spots at both loops ends, represent the gas accumulated by the falling motion along the loops, subsequent to magnetic flotation by the Parker instability. We have carried out sensitive CO observations of the foot points toward l=356 deg at a few pc resolution in the six rotational transitions of CO; 12CO(J=1-0, 3-2, 4-3, 7-6), 13CO(J=1-0) and C18O(J=1-0). The high resolution image of 12CO (J=3-2) has revealed the detailed distribution of the high excitation gas including U shapes, the outer boundary of which shows sharp intensity jumps accompanying strong velocity gradients. An analysis of the multi-J CO transitions shows that the temperature is in a range from 30-100 K and density is around 10^3-10^4 cm^-3, confirming that the foot points have high temperature and density although there is no prominent radiative heating source such as high mass stars in or around the loops. We argue that the high temperature is likely due to the shock heating under C-shock condition caused by the magnetic flotation. We made a comparison of the gas distribution with theoretical numerical simulations and note that the U shape is consistent with numerical simulations. We also find that the region of highest temperature of ~100 K or higher inside the U shape corresponds to the spur having an upward flow, additionally heated up either by magnetic reconnection or bouncing in the interaction with the narrow neck at the bottom of the U shape. We note these new findings further reinforce the magnetic floatation interpretation.Comment: 40 pages, 23 figures, accepted by PASJ on Vol.62 No.

Establishment of repeated liver biopsy technique in experimental mice

Biopsy is a commonly used method for determining pathological diagnoses by directly using human tissues and cells. Biopsies are widely used to determine disease progression and treatment efficacy. Although organs and tissues are usually obtained by sacrifice during animal experiments, it is theoretically possible to use the same biopsy techniques in humans. In the present study, we examined the feasibility of performing four repeated liver biopsies in a spontaneous metabolic syndrome mouse model. Even though a small number of mice died accidently, most mice were able to undergo four liver biopsies without significant adverse events. We also performed three liver biopsies in mouse liver tumor carcinogen models at 4, 8, and 12 weeks of age. In addition to the sample collected at 16 weeks of age during sacrifice, we successfully collected four liver samples from the same mice at different stages of disease progression. The application of this liver biopsy technique might make it possible for direct evaluation of pathological conditions in the same individual over time, thereby reducing the number of experimental animals

Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice

Male Tsumura-Suzuki Obese Diabetes (TSOD) mice, a spontaneous metabolic syndrome model, develop non-alcoholic steatohepatitis and liver tumors by feeding on a standard mouse diet. Nearly 70% of liver tumors express glutamine synthetase (GS), a marker of hepatocellular carcinoma. In contrast, approximately 30% are GS-negative without prominent nuclear or structural atypia. In this study, we examined the characteristics of the GS-negative tumors of TSOD mice. Twenty male TSOD mice were sacrificed at 40 weeks and a total of 21 tumors were analyzed by HE staining and immunostaining of GS, liver fatty acid-binding protein (L FABP), serum amyloid A (SAA), and beta-catenin. With immunostaining for GS, six (29%) tumors were negative. Based on the histological and immunohistological characteristics, six GS-negative tumors were classified into several subtypes of human hepatocellular adenoma (HCA). One large tumor showed generally similar findings to inflammatory HCA, but contained small atypical foci with GS staining and partial nuclear beta-catenin expression suggesting malignant transformation. GS-negative tumors of TSOD mice contained features similar to various subtypes of HCA. Different HCA subtypes occurring in the same liver have been reported in humans; however, the diversity of patient backgrounds limits the ability to conduct a detailed, multifaceted analysis. TSOD mice may share similar mechanisms of HCA development as in humans. It is timely to review the pathogenesis of HCA from both genetic and environmental perspectives, and it is expected that TSOD mice will make further contributions in this regard

RETRACTED: The Chromatin-Remodeling Complex WINAC Targets a Nuclear Receptor to Promoters and Is Impaired in Williams Syndrome

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the Authors.Our paper reported that a chromatin-remodeling complex, WINAC, recruited the unliganded vitamin D receptor to promoters in cooperation with the transcription factor implicated in Williams syndrome, WSTF. The findings provided insights into the coordination between chromatin remodelers and sequence-specific transcription factors and pointed to a role of chromatin remodeling defects in Williams syndrome. We recently identified errors affecting several figure panels where original data were processed inappropriately such that the figure panels do not accurately report the original data. We believe that the most responsible course of action is to retract the paper. We sincerely apologize to the scientific community for any inconvenience that this might cause. The first author, H.K., declined to sign the retraction notice

Peritoneoscopy of alcoholic liver cirrhosis in comparison with non-alcoholic liver cirrhosis.

Peritoneoscopic findings of 39 patients with alcoholic liver cirrhosis (ALC) were compared with those of 95 patients with non-alcoholic liver cirrhosis (NALC). They were selected from 245 patients with liver cirrhosis subjected to peritoneoscopy in the 7 year period from 1975 to 1981. Out of the 95 NALC patients, 24 had hepatitis B surface antigen. The ALC patients had nodules which varied in size (61%), large depressions (69%), and a markedly rounded edge of the liver (33%) more often than NALC patients (18, 43 and 3%, respectively). Nodularity differed between the right and left lobes in ALC (41%) more often than in NALC (16%). Interstitial reddish markings and patchy nodules were, however, more frequent in NALC (51 and 28%, respectively) than in ALC (8 and 5%, respectively). Lymphatic vesicles were observed both in ALC (85%) and NALC (78%). In conclusion, the peritoneoscopic features which suggested ALC were the coexistence of nodules of various sizes, large depressions and a markedly dull edge of the liver. Interstitial reddish markings and patchy nodules were more indicative of NALC than ALC.</p

Comparative diagnosis of alcoholic liver diseases by multivariate and histological analysis.

Sixty-seven cases of alcoholic liver disease were histologically classified into 4 groups: alcoholic liver cirrhosis (ALC), alcoholic hepatitis (AH), alcoholic liver fibrosis (ALF) and alcoholic fatty liver (AFL). They were statistically reclassified by the likelihood method using age, total alcohol intake, hepatomegaly and 12 liver function tests. A score table for likely diagnosis was constructed from the incidences of each range. The cases were re-evaluated using the score table, with an overall correct diagnosis rate of 73%. The best combination of 5 parameters included the indocyanine green plasma disappearance rate, total alcohol intake, cholesterol, choline esterase and glutamic oxaloacetic transaminase/glutamic pyruvic transaminase ratio. A correct diagnosis rate of 75% was attained using these 5 parameters, and 94% of patients were correctly diagnosed by the first or the second likelihood diagnosis. Differential diagnosis of alcoholic liver diseases was easily and confidently obtained with the likelihood score table.</p