ELF-MF Stimulates Adrenal Steroidogenesis

Extremely low-frequency magnetic fields (ELF-MFs) are generated by power lines and household electrical devices. In the last several decades, some evidence has shown an association between ELF-MF exposure and depression and/or anxiety in epidemiological and animal studies. The mechanism underlying ELF-MF-induced depression is considered to involve adrenal steroidogenesis, which is triggered by ELF-MF exposure. However, how ELF-MFs stimulate adrenal steroidogenesis is controversial. In the current study, we investigated the effect of ELF-MF exposure on the mouse adrenal cortex-derived Y-1 cell line and the human adrenal cortex-derived H295R cell line to clarify whether the ELF-MF stimulates adrenal steroidogenesis directly. ELF-MF exposure was found to significantly stimulate adrenal steroidogenesis (p < 0.01–0.05) and the expression of adrenal steroid synthetic enzymes (p < 0.05) in Y-1 cells, but the effect was weak in H295R cells. Y-1 cells exposed to an ELF-MF showed significant decreases in phosphodiesterase activity (p < 0.05) and intracellular Ca2+ concentration (p < 0.01) and significant increases in intracellular cyclic adenosine monophosphate (cAMP) concentration (p < 0.001–0.05) and cAMP response element-binding protein phosphorylation (p < 0.05). The increase in cAMP was not inhibited by treatment with NF449, an inhibitor of the Gs alpha subunit of G protein. Our results suggest that ELF-MF exposure stimulates adrenal steroidogenesis via an increase in intracellular cAMP caused by the inhibition of phosphodiesterase activity in Y-1 cells. The same mechanism may trigger the increase in adrenal steroid secretion in mice observed in our previous study

Busulfan for lymphoma with CNS involvement

The prognosis of relapsed or refractory lymphoma with central nervous system (CNS) involvement remains poor because of the lack of anticancer drugs with sufficient CNS penetration. [Case 1] A 65-year-old man was diagnosed with Stage IV mantle cell lymphoma. After two courses of chemotherapy and autologous hematopoietic stem cell (HSC) collection, urinary retention with fever developed. Cerebrospinal fluid analysis revealed leptomeningeal involvement, which was refractory to high-dose methotrexate therapy. Autologous peripheral blood stem cell transplantation (ASCT) was performed, followed by intravenous busulfan (ivBU), cyclophosphamide, and etoposide ; thereafter, no relapse has been detected for over six years. [Case 2] A 40-year-old woman with right lower hemiplegia was diagnosed with primary CNS lymphoma. Although four courses of high-dose methotrexate therapy were administered, the cerebral tumor increased in size. HSCs were collected after methotrexate therapy, and ASCT was performed in addition to conditioning using ivBU, cyclophosphamide, and etoposide, followed by whole-brain and local boost irradiation. She achieved complete remission, but relapsed two years after ASCT. High-dose ivBU-containing conditioning regimens with ASCT may be useful for refractory B-cell lymphoma with CNS involvement

気管・気管支内腔に多発ポリープ様病変を呈した小細胞癌の１例

It is rare that small cell carcinoma has multiple polypoid lesions. There is few report of small cell carcinoma in trachea and bronchus. We experienced a case of multiple polypoid lesions of small cell carcinoma. In January ２０１X, Woman in ６０s had operation for esophageal squamous cell carcinoma. In July ２０１X, thoracic and abdominal CT for postoperative follow-up revealed many nodules in the trachea, the bronchus, the lungs, and the liver, and mediastinum lymphadenopathy. We examined bronchoscopy and there were multiple polypoid lesions in the trachea and bronchus. Left main bronchus were almost occluded by maximum lesion, and we performed biopsy. We suspected recurrence of esophageal squamous cell carcinoma, therefore quickly started chemotherapy（CDDP＋５‐FU）and radiation for the left main bronchus. However, the pathological diagnosis was small cell carcinoma, we stopped the chemotherapy for esophageal squamous cell carcinoma. This case suggests we should examine to differentiate primary tumor or metastasis when we find a new lesion

Exposure to an Extremely-Low-Frequency Magnetic Field Stimulates Adrenal Steroidogenesis via Inhibition of Phosphodiesterase Activity in a Mouse Adrenal Cell Line

<div><p>Extremely low-frequency magnetic fields (ELF-MFs) are generated by power lines and household electrical devices. In the last several decades, some evidence has shown an association between ELF-MF exposure and depression and/or anxiety in epidemiological and animal studies. The mechanism underlying ELF-MF-induced depression is considered to involve adrenal steroidogenesis, which is triggered by ELF-MF exposure. However, how ELF-MFs stimulate adrenal steroidogenesis is controversial. In the current study, we investigated the effect of ELF-MF exposure on the mouse adrenal cortex-derived Y-1 cell line and the human adrenal cortex-derived H295R cell line to clarify whether the ELF-MF stimulates adrenal steroidogenesis directly. ELF-MF exposure was found to significantly stimulate adrenal steroidogenesis (p < 0.01–0.05) and the expression of adrenal steroid synthetic enzymes (p < 0.05) in Y-1 cells, but the effect was weak in H295R cells. Y-1 cells exposed to an ELF-MF showed significant decreases in phosphodiesterase activity (p < 0.05) and intracellular Ca²⁺ concentration (p < 0.01) and significant increases in intracellular cyclic adenosine monophosphate (cAMP) concentration (p < 0.001–0.05) and cAMP response element-binding protein phosphorylation (p < 0.05). The increase in cAMP was not inhibited by treatment with NF449, an inhibitor of the Gs alpha subunit of G protein. Our results suggest that ELF-MF exposure stimulates adrenal steroidogenesis via an increase in intracellular cAMP caused by the inhibition of phosphodiesterase activity in Y-1 cells. The same mechanism may trigger the increase in adrenal steroid secretion in mice observed in our previous study.</p></div

Exposure to an Extremely-Low-Frequency Magnetic Field Stimulates Adrenal Steroidogenesis via Inhibition of Phosphodiesterase Activity in a Mouse Adrenal Cell Line - Fig 6

<p><b>Signaling pathways regulating adrenal steroidogenesis (A) and the assumed steroidogenic mechanism induced by ELF-MF exposure (B).</b> AC: adenylate cyclase, cAMP: cyclic adenosine monophosphate, CaM: calmodulin, CaMK: calmodulin kinase, CREB: cAMP response element binding protein, DAG: diacylglycerol, GPCR: G protein-coupled receptor, IP3: inositol triphosphate, PDE: phosphodiesterase, PKA: protein kinase A, PKC: protein kinase C, PLC: phospholipase C, 5′ AMP: adenosine 5'-monophosphate.</p

Effects of ELF-MF and sham exposure on steroid secretion and enzyme expression in H295R cells.

<p>All data are presented as the mean ± S.E.M. Cortisol (A) and aldosterone (B) secretion did not show a significant difference between sham and ELF-MF exposure. (C) After 24 h of ELF-MF and sham exposure, mRNA expression of <i>Star</i> showed a significant increase in ELF-MF-exposed cells. (D) No significant increase was observed in protein levels. A representative blot image is shown (lanes 1 and 3: sham-exposed sample; lanes 2 and 4: ELF-MF-exposed sample). Steroid levels were quantified twice per sample (culture dish), and qRT-PCR and western blotting were performed once. n = 8 each, *p < 0.05, **p < 0.01.</p

Intracellular cAMP concentration was estimated in Y-1 cells exposed to ELF-MF and sham treatments.

<p>All data are presented as the mean ± S.E.M. (A) cAMP levels were significantly higher upon exposure to a 1.5-mT ELF-MF than after sham exposure for all durations (n = 8 each). (B) CREB phosphorylation was significantly higher in the ELF-MF group than in the sham group with 24 h of exposure (n = 8 each). (C) The 340/380 nm emission Fura ratio, which indicates [Ca²⁺]_i, was significantly lower in cells exposed to 24-h ELF-MF treatment (n = 10) than in sham-exposed cells (n = 10). cAMP levels were quantified twice per sample (dish). The Fura ratio was estimated once per sample. *p < 0.05, **p < 0.01, ***p < 0.001.</p

Effects of ELF-MF and sham exposure on steroid secretion and enzyme expression in Y-1 cells.

<p>Data are presented as the mean ± S.E.M. Corticosterone (A) and aldosterone (B) levels were significantly higher after 6 h of ELF-MF exposure. (C) <i>Cyp11a1</i> and <i>Cyp11b2</i> mRNA levels showed a significant increase after 24 h of exposure to the ELF-MF as indicated by qRT-PCR results. (D) Secreted CYP11A1 protein levels were significantly increased as indicated by western blotting. A representative blot image is shown (lanes 1 and 3: sham-exposed samples; lanes 2 and 4: ELF-MF- exposed samples). Steroids were quantified twice per sample (culture dish), and qRT-PCR and western blotting were performed once. n = 8 each, *p < 0.05, **p < 0.01 vs. sham exposure.</p

Effect of NF449 on the increase in cAMP concentration resulting from ELF-MF exposure.

<p>All data are presented as the mean ± S.E.M. (A) NF449 inhibited the increase in cAMP concentration in Y-1 cells exposed to sham treatment and 1.5 mT ELF-MF for 6 h; however, the cAMP-increasing effect of ELF-MF was still significantly higher than that of the sham treatment after 30 μM NF449 treatment (n = 8 each). (B) PDE activity was significantly lower in ELF-MF- than in sham-exposed Y-1 cells at both 6 h and 24 h (n = 4 each). cAMP and PDE were quantified twice per sample. *p < 0.05, **p < 0.01.</p