Alpha-fetoprotein-producing gastric carcinoma: Biological properties of a cultured cell line

We describe a gastric carcinoma cell line that has been maintained in vitro for more than 10 years and retains the capacity to produce a large amount of alpha-fetoprotein. This cell line was isolated from a metastatic lymph node of a 63-year-old male patient with advanced gastric carcinoma (T2N3P0H0M0) who showed high serum levels of alpha-fetoprotein. The primary tumor was moderately differentiated tubular adenocarcinoma and the lymph node was poorly differentiated adenocarcinoma without any particular pattern. The cultured cells grew as densely packed islet-like colonies with small polygonal cells. Electron microscopy revealed cells abundant in cytoplasmic organelles, with some cellular attachments being tight with junctional complexes and some being loose across intercellular spaces. The free cell surface had microvilli. The population doubling-time was 152 h at passage 58. Chromosomal analysis revealed the modal number to be 77, with numerous karyotype abnormalities. The tumorigenicity of the cultured cells in athymic nude mice was positive only when they were subcutaneously transplanted beneath a plastic plate, but when the cells were transplanted subcutaneously or administered by intrasplenic injection in intact or weakly irradiated nude mice, no tumorigenicty was shown. The cell line produced tumor-associated antigens, such as alpha-fetoprotein, carcinoembryonic antigen, and tissue polypeptide antigen. This cell line may be useful for comparative studies of different types of gastric carcinoma and alpha-fetoproteins of different origins.     

Voxel-based analysis of age and gender effects on striatal [123I] FP-CIT binding in healthy Japanese adults

Annals of Nuclear Medicine - Although previous studies have investigated age and gender effects on striatal subregional dopamine transporter (DaT) binding, these studies were mostly based on a...     

Thymidine phosphorylase and angiogenesis in early stage esophageal squamous cell carcinoma

Background

The relationship between thymidine phosphorylase (TP) and angiogenesis at the early stage of esophageal squamous cell carcinoma has been unclear.

Methods

Using 14 samples of normal squamous epithelium, 11 samples of low-grade intraepithelial neoplasia, and 64 samples of superficial esophageal cancer, microvessel density (MVD) was estimated using immunostaining for CD34 and CD105. TP expression was also evaluated in both cancer cells and stromal monocytic cells (SMCs). We then investigated the correlation between MVD and TP expression in both cancer cells and SMCs.

Results

On the basis of the above parameters, MVD was significantly higher in cancerous lesions than in normal squamous epithelium. In terms of CD34 and CD105 expression, MVD showed a gradual increase from normal squamous epithelium, to low-grade intraepithelial neoplasia, and then to M1 and M2 cancer, and M3 or deeper cancer. M1 and M2 cancer showed overexpression of TP in both cancer cells and SMCs. There was no significant correlation between TP expression in cancer cells and MVD estimated from CD34 (rS = 0.16, P = 0.21) or CD105 (rS = 0.05, P = 0.68) expression. Significant correlations were found between TP expression in SMCs and CD34-related (rS = 0.46, P < 0.001) and CD105-related (rS = 0.34, P < 0.01) MVD. In M3 or deeper cancers, there were no significant correlations between TP expression in cancer cells or SMCs and venous invasion, lymphatic invasion, and lymph node metastasis.

Conclusion

TP expression is activated in both cancer cells and stromal monocytic cells at the very early stage of ESCC progression. TP expression in SMCs, rather than in cancer cells, is significantly correlated with angiogenesis.

     

Incidence of human parvovirus B19 DNA detection in blood donors

Summary. 1000 serum samples from blood donors were tested for human parvovirus B19 (B19) DNA by a nested PCR assay: six samples were positive for B19 DNA. The frequency was 1/167 (0-6%), considerably higher than previous surveys (0-004-0-03%). Five of the six samples were also positive for anti-B19 IgM, indicating an acute phase of infection. It is recommended to screen for B19 DNA in blood products to prevent transfusion mediated viral infection for those susceptible such as immunocompromised patients and pregnant women.     

Transforming growth factor-β receptor antagonism attenuates myocardial fibrosis in mice with cardiac-restricted overexpression of tumor necrosis factor

The mechanisms that are responsible for the development of myocardial fibrosis in inflammatory cardiomyopathy are unknown. We have previously generated lines of transgenic mice with cardiac-restricted overexpression of tumor necrosis factor (MHCsTNF mice), a pro-inflammatory cytokine. The MHCsTNF mice develop a heart failure phenotype that is characterized by progressive myocardial fibrosis, as well as increased levels transforming growth factor-β (TGF-β)(mRNA and protein. In order to determine whether TGF-β-mediated signaling was responsible for the myocardial fibrosis observed in the MHCsTNF mice, we treated MHCsTNF and littermate control mice from 4 to 12 weeks of age with a novel orally available TGF-β receptor antagonist (NP-40208). At the time of terminal study, myocardial collagen content was determined using the picrosirius red technique, and left ventricular (LV) systolic and diastolic function were determined using the Langendorff method. Treatment with NP-40208 resulted in a significant (P < 0.05) 65% decrease in nuclear translocation of Smad 2/3, a significant (P < 0.05), decrease in the heart-weight to body-weight ratio from 6.5 to 5.7, a ∼37% decrease in fibrillar collagen content (P < 0.01) and a significant (P < 0.05) decrease in the LV chamber stiffness by ∼25% in the MHCsTNF mice when compared to diluent-treated controls. Treatment with NP-40208 had no discernable effect on LV systolic function, nor any effect on cardiac myocyte size or fetal gene expression in the MHCsTNF mice. Taken together, these observations suggest that sustained pro-inflammatory signaling in the adult heart is associated with a pro-fibrotic phenotype that arises, at least in part, from TGF-β-mediated signaling, with resultant activation of Smad 2/3, leading to increased myocardial fibrosis and increased LV diastolic chamber stiffness. Returned for 1. revision: 29 August 2007 1. Revision received: 24 September 2007     

Attenuated Apoptosis in H. pylori-Colonized Gastric Mucosa of Mongolian Gerbils in Comparison with Mice

Although gastric cancer formation with H. pylori in Mongolian gerbils was recently reported, the same inoculation procedure did not result in cancer formation in other animals such as mice. Disturbed regulation of apoptosis and cell proliferation are known to link the multistep process of carcinogenesis. The present study is designed to examine the level of gastric epithelial cell apoptosis in Mongolian gerbils colonized with the H. pylori (Sydney strain: SS1) in comparison with that in mice. Mice (C57BL/6) and Mongolian gerbils were orally inoculated with SS1 and the stomachs were examined 9 and 18 months later. MPO activity increased persistently in gerbils, but increased transiently in mice. While the levels of DNA fragmentation, caspase-3 activity, and the number of TUNEL-positive cells increased significantly in mice, such parameters were attenuated in gerbils. On the other hand, the number of PCNA-positive cells increased after SS1 inoculation only in Mongolian gerbils, suggesting the enhancement of cell turnover in H. pylori-colonized gerbils. In conclusion, the SS1-induced increase in gastric mucosal apoptosis observed in mice was attenuated significantly in Mongolian gerbils, suggesting the causative role for the higher incidence of gastric carcinogenesis in this animal.     

Cyp11b1 is induced in the murine gonad by luteinizing hormone/human chorionic gonadotropin and involved in the production of 11-ketotestosterone, a major fish androgen: conservation and evolution of the androgen metabolic pathway

We have shown previously that Cyp11b1, an 11beta-hydroxylase responsible for glucocorticoid biosynthesis in the adrenal gland, was induced by cAMP in androgen-producing Leydig-like cells derived from mesenchymal stem cells. We found that Cyp11b1 was induced in male Leydig cells, or female theca cells, when human chorionic gonadotropin was administered in immature mice. Expression of Cyp11b1 in rodent gonads caused the production of 11-ketotestosterone (11-KT), a major fish androgen, which induces male differentiation or spermatogenesis in fish. As in teleosts, plasma concentrations of 11-KT were elevated in human chorionic gonadotropin-treated mice. In contrast to teleosts, however, plasma concentrations of 11-KT were similar in both sexes, despite levels of testosterone, a precursor substrate, being about 20 times higher in male mice. Because expression of 11beta-hydroxysteroid dehydrogenase type 2, was much higher in the mouse ovary than in the testis, conversion of testosterone into 11-KT may occur more efficiently in the ovary. In a luciferase reporter system that was responsive to and activated by androgens, 11-KT efficiently activated mammalian androgen receptor-mediated transactivation. Our results suggest that the androgen metabolic pathway is conserved between teleosts and mammals, despite sexual dominance and reproductive functions of 11-KT being altered during evolution.     

Antimicrobial susceptibility tests and resistant strain of Helicobacter pylori

The antimicrobial susceptibility test was necessary for the eradication therapy of Helicobacter pylori infections. This is because, clarithromycin resistant strains has became an increasing problem. In this study, we used the antimicrobial susceptibility test which was compare with the agar gradient method, Etest, and broth microdilution method (dry plate) with 4 antimicrobial agents. The results strongly suggested that broth microdilution method was the best method in order to test the antimicrobial susceptibility of H. pylori. On the other hand, 393 H. pylori stains isolated during 1994-1998 from clinical patients were tested for antimicrobial susceptibility test to amoxicillin, clarithromycin, metronidazole, and minomycin. There were no resistant strains to amoxicillin and minomycin. But clarithromycin and Metronidazole resistant strains were recognized in 85 (22.0%) and 36 (21.7%) strains.     

Electrocardiographic characteristics of repetitive monomorphic right ventricular tachycardia originating near the His-bundle

INTRODUCTION: Most idiopathic nonreentrant ventricular tachycardia (VT) and ventricular premature contractions (VPCs) arise from the right or left ventricular outflow tract (OT). However, some right ventricular (RV) VT/VPCs originate near the His-bundle region. The aim of this study was to investigate ECG characteristics of VT/VPCs originating near the His-bundle in comparison with right ventricular outflow tract (RVOT)-VT/VPCs. METHODS AND RESULTS: Ninety RV-VT/VPC patients underwent catheter mapping and radiofrequency ablation. ECG variables were compared between VT/VPCs originating from the RVOT and near the His-bundle. Ten patients had foci near the His-bundle (HIS group), with the His-bundle local ventricular electrogram preceding the QRS onset by 15-35 msec (mean: 22 msec) and His-bundle pacing produced a nearly identical ECG to clinical VT/VPCs. The HIS group R wave amplitude in the inferior leads (lead III: 1.0 +/- 0.6 mV) was significantly lower than that of the RVOT group (1.7 +/- 0.4 mV, P < 0.05). An R wave in aVL was present in 6 of 10 HIS group patients, while almost all RVOT group patients had a QS pattern in aVL. Lead I in HIS group exhibited significantly taller R wave amplitudes than RVOT group. HIS group QRS duration in the inferior leads was shorter than that of the RVOT group. Eight of 10 HIS group patients exhibited a QS pattern in lead V1 compared to 14 of 81 RVOT group patients. HIS group had larger R wave amplitudes in leads V5 and V6 than RVOT group. CONCLUSION: VT/VPCs originating near the His-bundle have distinctive ECG characteristics. Knowledge of the characteristic QRS morphology may facilitate catheter mapping and successful ablation.     

Restoration of ultraviolet-induced unscheduled DNA synthesis of xeroderma pigmentosum cells by the concomitant treatment with bacteriophage T4 endonuclease V and HVJ (Sendai virus).

Ultraviolet (UV)-induced unscheduled DNA synthesis of xeroderma pigmentosum cells, belonging to complementation groups A, B, C, D, and E, was restored to the normal level by concomitant treatment of the cells with T4 endonuclease V and UV-inactivated HVJ (Sendai virus). The present results suggest that (1) T4 endonuclease molecules were inserted effectively into the cells by the interaction of HVJ with the cell membranes, (2) the enzyme was functional on human chromosomal DNA which had been damaged by UV irradiation in the viable cells, (3) all the studied groups of xeroderma pigmentosum ("variant" was not tested) were defective in the first step (incision) of excision repair.