Primary Gastrointestinal Stromal Tumor of the Liver with Cystic Changes

Gastrointestinal stromal tumors (GISTs) are known to originate specifically from the intestinal cells of Cajal located in the gastrointestinal mesenchyme. GISTs developing outside of the digestive tract have barely been reported. We encountered a first case of large primary GISTs in the liver with cystic changes. A 63-year-old man with a past history of brain infarction visited our hospital. The computed tomography (CT) revealed a 6-cm and a 10-cm mass in the right and the caudal lobe of the liver, respectively. These tumors have marginal enhancement in the arterial phase; however, they presented as hypodense in the internal tumor sites. Both liver tumors had cystic changes. Gastrointestinal examinations using endoscopy revealed no other gastrointestinal tumors, and [18F]-fluoro-2-deoxy-D-glucose positron emission tomography/CT revealed multiple bone metastases in addition to the liver tumors. The liver tumor specimens were composed of spindle cells, and the immunohistochemical staining for c-Kit and for DOG1, as discovered on GIST, was positive. The patient was diagnosed with primary hepatic GIST with cystic changes

Visceral fat obesity is the key risk factor for the development of reflux erosive esophagitis in 40–69-years subjects

[Background] Visceral fat obesity can be defined quantitatively by abdominal computed tomography, however, the usefulness of measuring visceral fat area to assess the etiology of gastrointestinal reflux disease has not been fully elucidated. [Methods] A total of 433 healthy subjects aged 40–69 years (234 men, 199 women) were included in the study. The relationship between obesity-related factors (total fat area, visceral fat area, subcutaneous fat area, waist circumference, and body mass index) and the incidence of reflux erosive esophagitis was investigated. Lifestyle factors and stomach conditions relevant to the onset of erosive esophagitis were also analyzed. [Results] The prevalence of reflux erosive esophagitis was 27.2% (118/433; 106 men, 12 women). Visceral fat area was higher in subjects with erosive esophagitis than in those without (116.6 cm2 vs. 64.9 cm2, respectively). The incidence of erosive esophagitis was higher in subjects with visceral fat obesity (visceral fat area ≥ 100 cm2) than in those without (61.2% vs. 12.8%, respectively). Visceral fat obesity had the highest odds ratio (OR) among obesity-related factors. Multivariate analysis showed that visceral fat area was associated with the incidence of erosive esophagitis (OR = 2.18), indicating that it is an independent risk factor for erosive esophagitis. In addition, daily alcohol intake (OR = 1.54), gastric atrophy open type (OR = 0.29), and never-smoking history (OR = 0.49) were also independently associated with the development of erosive esophagitis. [Conclusions] Visceral fat obesity is the key risk factor for the development of reflux erosive esophagitis in subjects aged 40–69 years

Tunicate cytostatic factor TC14-3 induces a polycomb group gene and histone modification through Ca2+ binding and protein dimerization

<p>Abstract</p> <p>Background</p> <p>As many invertebrate species have multipotent cells that undergo cell growth and differentiation during regeneration and budding, many unique and interesting homeostatic factors are expected to exist in those animals. However, our understanding of such factors and global mechanisms remains very poor. Single zooids of the tunicate, <it>Polyandrocarpa </it><it>misakiensis</it>, can give off as many as 40 buds during the life span. Bud development proceeds by means of transdifferentiation of very limited number of cells and tissues. TC14-3 is one of several different but closely related polypeptides isolated from <it>P. misakiensis</it>. It acts as a cytostatic factor that regulates proliferation, adhesion, and differentiation of multipotent cells, although the molecular mechanism remains uncertain. The Polycomb group (PcG) genes are involved in epigenetic control of genomic activity in mammals. In invertebrates except <it>Drosophila</it>, PcG and histone methylation have not been studied so extensively, and genome-wide gene regulation is poorly understood.</p> <p>Results</p> <p>When Phe⁶⁵of TC14-3 was mutated to an acidic amino acid, the resultant mutant protein failed to dimerize. The replacement of Thr⁶⁹with Arg⁶⁹made dimers unstable. When Glu¹⁰⁶was changed to Gly¹⁰⁶, the resultant mutant protein completely lost Ca²⁺binding. All these mutant proteins lacked cytostatic activity, indicating the requirement of protein dimerization and calcium for the activity. <it>Polyandrocarpa </it><it>Eed</it>, a component of PcG, is highly expressed during budding, like TC14-3. When wild-type and mutant TC14-3s were applied in vivo and in vitro to <it>Polyandrocarpa </it>cells, only wild-type TC14-3 could induce <it>Eed </it>without affecting histone methyltransferase gene expression. Eed-expressing cells underwent trimethylation of histone H3 lysine27. <it>PmEed </it>knockdown by RNA interference rescued cultured cells from the growth-inhibitory effects of TC14-3.</p> <p>Conclusion</p> <p>These results show that in <it>P. misakiensis</it>, the cytostatic activity of TC14-3 is mediated by <it>PmEed </it>and resultant histone modification, and that the gene expression requires both the protein dimerization and Ca²⁺-binding of TC14-3. This system consisting of a humoral factor, PcG, and histone methylation would contribute to the homeostatic regulation of cell growth and terminal differentiation of invertebrate multipotent cells.</p

Mortality Sensitivity of Cardiovascular, Cerebrovascular, and Respiratory Diseases to Warm Season Climate in Japanese Cities

We investigated decadal (2010–2019) cardiovascular, cerebrovascular, and respiratory mortality sensitivity to annual warm temperatures in major Japanese cities: Sapporo, Tokyo (23 wards), and Osaka. The summer mortalities (June–August) increased with the monthly mean temperature for acute myocardial infarction, other acute ischemic heart diseases, cerebral infarction, and pneumonia in the three cities. Monthly mean temperatures were an indicator of these disease mortalities in Japan. However, similar responses were not found for cardiac arrhythmia and heart failure (excluding Sapporo), subarachnoid hemorrhage, and intracerebral hemorrhage. The decadal sensitivities and risk ratios between the maximum and minimum monthly mean temperatures were calculated using a linear regression model. In Sapporo, Tokyo, and Osaka, for example, the analyses of acute myocardial infarction showed summer positive responses of 0.19–0.25, 0.13–0.18, and 0.12–0.30, respectively, as the mortality rate (per 100,000 population) per 1 °C of monthly mean temperature, which estimated increased risks (between the coolest and hottest months) of 37–65% in Sapporo, 31–42% in Tokyo, and 35–39% in Osaka

The fission yeast Pvg1p has galactose-specific pyruvyltransferase activity

AbstractN-Glycan from the fission yeast Schizosaccharomyces pombe contains outer-chain pyruvic acid 4,6-ketal-linked galactose (PvGal). Here, we characterized a putative S. pombe pyruvyltransferase, Pvg1p, reported to be essential for biosynthesis of PvGal. When p-nitrophenyl-β-Gal (pNP-β-Gal) was used as a substrate, the structure of the recombinant Pvg1p product was determined to be pNP-PvGal by one- and two-dimensional NMR spectroscopy. The recombinant Pvg1p transferred pyruvyl residues from phosphoenolpyruvate specifically to β-linked galactose

Histidine Kinase Homologs That Act as Cytokinin Receptors Possess Overlapping Functions in the Regulation of Shoot and Root Growth in Arabidopsis

Cytokinins are plant hormones that may play essential and crucial roles in various aspects of plant growth and development. Although the functional significance of exogenous cytokinins as to the proliferation and differentiation of cells has been well documented, the biological roles of endogenous cytokinins have remained largely unknown. The recent discovery of the Arabidopsis Histidine Kinase 4 (AHK4)/CRE1/WOL cytokinin receptor in Arabidopsis thaliana strongly suggested that the cellular response to cytokinins involves a two-component signal transduction system. However, the lack of an apparent phenotype in the mutant, presumably because of genetic redundancy, prevented us from determining the in planta roles of the cytokinin receptor. To gain insight into the molecular functions of the three AHK genes AHK2, AHK3, and AHK4 in this study, we identified mutational alleles of the AHK2 and AHK3 genes, both of which encode sensor histidine kinases closely related to AHK4, and constructed a set of multiple ahk mutants. Application of exogenous cytokinins to the resultant strains revealed that both AHK2 and AHK3 function as positive regulators for cytokinin signaling similar to AHK4. The ahk2 ahk4 and ahk3 ahk4 double mutants and the ahk single mutants grew normally, whereas the ahk2 ahk3 double mutants exhibited a semidwarf phenotype as to shoots, such as a reduced leaf size and a reduced influorescence stem length. The growth and development of the ahk2 ahk3 ahk4 triple mutant were markedly inhibited in various tissues and organs, including the roots and leaves in the vegetative growth phase and the influorescence meristem in the reproductive phase. We showed that the inhibition of growth is associated with reduced meristematic activity of cells. Expression analysis involving AHK:β-glucuronidase fusion genes suggested that the AHK genes are expressed ubiquitously in various tissues during postembryonic growth and development. Our results thus strongly suggest that the primary functions of AHK genes, and those of endogenous cytokinins, are triggering of the cell division and maintenance of the meristematic competence of cells to prevent subsequent differentiation until a sufficient number of cells has accumulated during organogenesis

The A-Type Cyclin CYCA2;3 Is a Key Regulator of Ploidy Levels in Arabidopsis Endoreduplication

Plant cells frequently undergo endoreduplication, a process in which chromosomal DNA is successively duplicated in the absence of mitosis. It has been proposed that endoreduplication is regulated at its entry by mitotic cyclin-dependent kinase activity. However, the regulatory mechanisms for its termination remain unclear, although plants tightly control the ploidy level in each cell type. In the process of searching for regulatory factors of endoreduplication, the promoter of an Arabidopsis thaliana cyclin A gene, CYCA2;3, was revealed to be active in developing trichomes during the termination period of endoreduplication as well as in proliferating tissues. Taking advantage of the situation that plants encode highly redundant cyclin A genes, we were able to perform functional dissection of CYCA2;3 using null mutant alleles. Null mutations of CYCA2;3 semidominantly promoted endocycles and increased the ploidy levels achieved in mature organs, but they did not significantly affect the proportion of cells that underwent endoreduplication. Consistent with this result, expression of the CYCA2;3–green fluorescent protein fusion protein restrained endocycles in a dose-dependent manner. Moreover, a mutation in the destruction box of CYCA2;3 stabilized the fusion protein in the nuclei and enhanced the restraint. We conclude that CYCA2;3 negatively regulates endocycles and acts as a key regulator of ploidy levels in Arabidopsis endoreduplication