Environment: Peculiar Pigment Cell Neoplasm in Fish

Chromatophoroma in the croaker (Nibea mitsukurii) showed a unique geographic distribution. The contribution of environmental chemicals to the cause of chromatophoroma in the feral croaker is considered likely on the basis of the following results in our studies. 1) Chromatophoroma was induced in tank-reared N. mitsukurii by administration of certain kinds of known carcinogens such as 7,12-dimethyl-benz(a)anthra-cene, N-methyl-N'-nitro-N-nitrosoguanidine, and nifurpirinol. 2) Local accumulation of pigment-cell hyperplasia in the catfish (Protosus anguillaris) showed similar tendencies to those of chromatophoroma in N. mitsukurii. 3) Removal of contaminated sediment from the harbor and the river appeared to reduce the incidence from 47% in 1973–1983 to about 20% in 1985–1987. 4) Waste water from a factory located at the station where the incidence of the neoplasm was the highest contained mutagenic substances such as chloroacetones and glyoxals [5]. Exposure of catfish to the waste water induced pigment-cell hyperplasia on the skin. J Invest Dermatol 92:248S–254S, 198

Regulation of Adrenal Aldosterone Production by Serine Protease Prostasin

A serine protease prostasin has been demonstrated to have a pivotal role in the activation of the epithelial sodium channel. Systemic administration of adenovirus carrying human prostasin gene in rats resulted in an increase in plasma prostasin and aldosterone levels. However, the mechanism by which the elevation of prostasin levels in the systemic circulation stimulated the plasma aldosterone levels remains unknown. Therefore, we examined if prostasin increases the aldosterone synthesis in a human adrenocortical cell line (H295R cells). Luciferase assay using CYP11B2 promoter revealed that prostasin significantly increased the transcriptional activity of CYP11B2. Prostasin significantly increased both CYP11B2 mRNA expression and aldosterone production in a dose-dependent manner. Surprisingly, treatment with camostat mesilate, a potent prostasin inhibitor, had no effect on the aldosterone synthesis by prostasin and also a protease-dead mutant of prostasin significantly stimulated the aldosterone production. A T-type/L-type calcium channel blocker and a protein kinase C (PKC) inhibitor significantly reduced the aldosterone synthesis by prostasin. Our findings suggest a stimulatory effect of prostasin on the aldosterone synthesis by adrenal gland through the nonproteolytic action and indicate a new role of prostasin in the systemic circulation

Gastrointestinal Stromal Tumor Mimicking Arteriovenous Malformation of the Jejunum

There have been case reports of small intestinal gastrointestinal stromal tumors (GISTs) complicated with arteriovenous malformation (AVM) and angiodysplasia and exhibiting intense tumor staining. Herein we report a GIST of the small intestine that showed tumor staining and early venous return on imaging studies, and so the patient was suspected to have AVM. A 62-year-old male presented with intermittent pain in the left abdominal region. Contrast-enhanced computed tomography revealed a 15-mm-long spindle-shaped mass showing intense tumor staining and early venous return through the jejunal vein. In the arterial phase, the attenuation value of the tumor was 250 Hounsfield units. Color Doppler ultrasonography simultaneously delineated vessels extending from the serosal side and turbulent signals showing a mosaic pattern in the tumor. On angiography, intense staining was observed in the peripheral part of the second branch of the jejunal artery. Although these findings suggested AVM, the tumor was diagnosed as a GIST based on pathological examination of the resected specimens. In this case, no AVM or change in vascular density was noted despite the careful examination of pathological specimens, and the cause of the tumor staining remained unknown

Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites

The p300 and CBP histone acetyltransferases are recruited to DNA double-strand break (DSB) sites where they induce histone acetylation, thereby influencing the chromatin structure and DNA repair process. Whether p300/CBP at DSB sites also acetylate non-histone proteins, and how their acetylation affects DSB repair, remain unknown. Here we show that p300/CBP acetylate RAD52, a human homologous recombination (HR) DNA repair protein, at DSB sites. Using in vitro acetylated RAD52, we identified 13 potential acetylation sites in RAD52 by a mass spectrometry analysis. An immunofluorescence microscopy analysis revealed that RAD52 acetylation at DSBs sites is counteracted by SIRT2- and SIRT3-mediated deacetylation, and that non-acetylated RAD52 initially accumulates at DSB sites, but dissociates prematurely from them. In the absence of RAD52 acetylation, RAD51, which plays a central role in HR, also dissociates prematurely from DSB sites, and hence HR is impaired. Furthermore, inhibition of ataxia telangiectasia mutated (ATM) protein by siRNA or inhibitor treatment demonstrated that the acetylation of RAD52 at DSB sites is dependent on the ATM protein kinase activity, through the formation of RAD52, p300/CBP, SIRT2, and SIRT3 foci at DSB sites. Our findings clarify the importance of RAD52 acetylation in HR and its underlying mechanism

Prefrontal cortex activation and young driver behaviour: a fNIRS study

Road traffic accidents consistently show a significant over-representation for young, novice and particularly male drivers. This research examines the prefrontal cortex activation of young drivers and the changes in activation associated with manipulations of mental workload and inhibitory control. It also considers the explanation that a lack of prefrontal cortex maturation is a contributing factor to the higher accident risk in this young driver population. The prefrontal cortex is associated with a number of factors including mental workload and inhibitory control, both of which are also related to road traffic accidents. This experiment used functional near infrared spectroscopy to measure prefrontal cortex activity during five simulated driving tasks: one following task and four overtaking tasks at varying traffic densities which aimed to dissociate workload and inhibitory control. Age, experience and gender were controlled for throughout the experiment. The results showed that younger drivers had reduced prefrontal cortex activity compared to older drivers. When both mental workload and inhibitory control increased prefrontal cortex activity also increased, however when inhibitory control alone increased there were no changes in activity. Along with an increase in activity during overtaking manoeuvres, these results suggest that prefrontal cortex activation is more indicative of workload in the current task. There were no differences in the number of overtakes completed by younger and older drivers but males overtook significantly more than females. We conclude that prefrontal cortex activity is associated with the mental workload required for overtaking. We additionally suggest that the reduced activation in younger drivers may be related to a lack of prefrontal maturation which could contribute to the increased crash risk seen in this population

P-selectin glycoprotein ligand-1 contributes to wound healing predominantly as a p-selectin ligand and partly as an e-selectin ligand.

Cell adhesion molecules are critical to wound healing through leukocyte recruitment. Although P-selectin glycoprotein ligand-1 (PSGL-1) regulates leukocyte rolling by binding P-selectin, but also binding E- and L-selectins with lower affinity, little is known about a role of PSGL-1 in wound healing. To clarify a role of PSGL-1 and its interaction with E- and P-selectins in wound healing, we investigated cutaneous wound healing in PSGL-1-deficient (PSGL-1(-/-)) mice in comparison with E-selectin(-/-), P-selectin(-/-), and P-selectin(-/-) mice treated with an anti-E-selectin antibody. PSGL-1 deficiency inhibited early wound healing, which was accompanied by decreased inflammatory cell infiltration and growth factor expression. By contrast, E-selectin deficiency did not affect wound healing. In general, the inhibitory effect of PSGL-1 deficiency on wound healing was similar to that of P-selectin deficiency either alone or with E-selectin blockade. However, early granulation tissue formation, late angiogenesis, and early infiltration of neutrophils and macrophages in PSGL-1(-/-) mice were inhibited beyond the inhibition in P-selectin(-/-) mice, but to a similar level of inhibition in P-selectin(-/-) mice with E-selectin blockade. These results suggest that PSGL-1 contributes to wound healing predominantly as a P-selectin ligand and partly as an E-selectin ligand by mediating infiltration of inflammatory cells

含糖酸化鉄注射液の長期投与でFGF23関連低リン血症性骨軟化症を来たしたクローン病の１例

症例は50歳代，男性．クローン病で２年前に右半結腸切除術，小腸部分切除を施行．術後に他院にてアダリムマブを導入され，クローン病は臨床的寛解の状態であった．４か月前より下肢を中心とした疼痛が出現した．アダリムマブによる薬剤起因性ループスあるいは腸炎性関節炎を疑い，２か月前よりアダリムマブ投与を中止し，プレドニゾロンの内服を開始するも改善を認めなかった．血液検査にて，低リン血症と高アルカリフォスファターゼ血症を認め，精査治療目的で当院に紹介入院となった．骨塩定量検査にて骨密度の低下を，骨シンチグラフィーで疼痛を認める骨への多発取り込みを認め，骨軟化症と診断した．血清のfibroblast growth factor 23（FGF23）が175pg/ml と高値であり，入院前まで定期的に使用されていた含糖酸化鉄注射液による，FGF23関連低リン血症性骨軟化症と診断した．含糖酸化鉄注射液投与を中止し，リン製剤とビタミンD 製剤の投与を開始したところ，徐々に低リン血症と高アルカリフォスファターゼ血症の改善を認めた．その後の経過は良好で，FGF23値は徐々に低下を示し，下肢を中心とした疼痛は軽快し，退院した．長期的に含糖酸化鉄注射液を投与する場合は，FGF23関連低リン血症の早期発見のため，血中リン濃度を定期的に測定する必要がある．The case is a man in his 50s. He underwent operations of right half colon resection and small intestine segmental resection due to Crohn’s disease two years ago. After surgery, Adalimumab was introduced in other hospital, and he was a state of the clinical remission in Crohn’s disease. The sharp pain mainly on lower limbs develops from four months ago. We doubted drug origin-related lupus with Adalimumab or enteritis-related joint pain. Therefore, we stopped Adalimumab injection and started internal use of the prednisolone, however the symptoms did not improve and had continued for two months.Laboratory test showed hypophosphatemia and hyperphosphatasemia and then he was transported to our hospital. Bone mineral quantity showed bone salt decrease and bone scan showed increased uptakes in multiple bones. Fibroblast growth factor23 (FGF23) of the serum was high (175pg/ml), and we diagnosed him FGF23-mediated hypophosphatemic osteomalasia induced by prolonged administration of saccharated ferric acid.Saccharated ferric acid has regularly been used until hospitalization. After stopping the ferric acid injection, and taking phosphorus and vitamin D, hypophosphatemia and hyperphosphatasemia was gradually improved. FGF23 level gradually reduced, and the sharp pain mainly on lower limbs was relieved, and it became a discharge. Regular measurement of serum phosphorus concentration is necessary for early detection of the FGF23-related hypophosphatemia in patients with long term use of saccharated ferric acid

生活水の中の重金属 : 煮沸により鍋から溶出する重金属 (II)(B. 生活科学)

煮沸による重金属溶出を6種類の鍋, すなわち, シリコン樹脂加工した鉄鍋, 錫びきの銅鍋, ホーロー鍋, ステンレス鍋, アルマイト鍋およびフッソ樹脂加工したアルミ鍋, について調べた。水の煮沸ではホーロー鍋だけが重金属の溶出を起こさなかった。しかし, 他の鍋からは全て1∿2種類の重金属の溶出がみられた。5%酢酸水溶液の煮沸では6種類の鍋全てから重金属溶出がみられ, しかもその量は水煮沸の4∿10倍にふえた。Release of heavy metals by boiling were investigated for the 6 kinds of pans, such as an iron pan coated with silicone, a copper one with tin, an enameled one, a pan of stainless steel, and two pans of aluminum alloy-coated with alumina and with fluoroplastic. By boiling-water only the enameled pan released no heavy metals, whereas all others one or two kinds of heavy metals. But by boiling the 5% solution of acetic acid all of 6 pans released heavy metals and the concentration of heavy metals increased by 4-10 times as much as the water-boiling released

日本の食物のアルミニウム含量 (I)(B. 生活科学)

Some authors have suggested that aluminum would significantly influence on causation of Alzheimer\u27s disease and would be a toxic material for human life. Informations on the ingestion of aluminum through a daily meal are needed for Japanese. Quantity of aluminum to be ingested was investigated in case of a usual meal which contained a cup of rice, a dish of pork-beans and a dish of Gomoku-mame. The investigation revealed that taking a meal of this menu resulted in the ingestion of aluminum of 3400μg