Localization of EFA6 (exchange factor for ARF6) isoform D in steroidogenic testicular Leydig cells of adult mice

EFA6 (exchange factor for ARF6) activates Arf6 (ADP ribosylation factor 6) by exchanging ADP to ATP and the resulting activated form of Arf6 is involved in the membrane trafficking and actin remodeling of cells. Our previous study has shown the selective expression/localization of EFA6D in steroidogenic adrenocortical cells in situ of adult mice. In view of the previous finding, the present study was undertaken to examine its localization in mouse Leydig cells representing another steroidogenic cell species in order to further support the possible involvement of the EFA6/Arf6 cascade via membrane trafficking in the regulation of steroidogenesis and/or secretion. A distinct band for EFA6D with the same size as that of the brain was detected in the testis of adult mice. In immuno-light microscopy, immunoreactivity for EFA6D was seen throughout the cytoplasm in most Leydig cells without any distinct accumulation along the plasmalemma. Lack of immunoreactivity for EFA6D was seen in the seminiferous tubular epithelium. In immuno-electron microscopy, the immune-labeling was seen in sporadic/focal patterns on plasma membranes and some vesicles and vacuoles subjacent to the plasma membranes. More constant and rather predominant is the labeling on numerous mitochondria. No immuno-labeling was seen in lipid droplets. The present study suggests that EFA6D is somehow involved in regulation of the synthesis and/or secretion of testosterone through the membrane-traffic by activation of Arf6. In addition, EFA6D is suggested to play in mitochondria some yet unidentified roles rather independent of Arf6-activation, which remains to be elucidated.     

Induction of hibernation-like hypothermia by central activation of the A1 adenosine receptor in a non-hibernator,the rat

Central adenosine A1-receptor (A1AR)-mediated signals play a role in the induction of hibernation. We determined whether activation of the central A1AR enables rats to maintain normal sinus rhythm even after their body temperature has decreased to less than 20 °C. Intracerebroventricular injection of an adenosine A1 agonist, N6-cyclohexyladenosine (CHA), followed by cooling decreased the body temperature of rats to less than 20 °C. Normal sinus rhythm was fundamentally maintained during the extreme hypothermia. In contrast, forced induction of hypothermia by cooling anesthetized rats caused cardiac arrest. Additional administration of pentobarbital to rats in which hypothermia was induced by CHA also caused cardiac arrest, suggesting that the operation of some beneficial mechanisms that are not activated under anesthesia may be essential to keep heart beat under the hypothermia. These results suggest that central A1AR-mediated signals in the absence of anesthetics would provide an appropriate condition for maintaining normal sinus rhythm during extreme hypothermia.     

A male case with CDKL5-associated encephalopathy manifesting transient methylmalonic acidemia

Mutations in the X-linked gene CDKL5 cause early-onset epileptic encephalopathy and severe developmental delay. Because this disorder predominantly affects females, the full clinical spectrum of male patients remains elusive. We herein report a 16-year-old boy, who suffered from intractable seizures 20 days after birth. Serial electroencephalograms detected recurrent focal epileptiform discharges from age 4 months, which evolved to hypsarrhythmia later in infancy. Mass-spectrometric analyses revealed increase in urinary excretion of methylmalonic acid without perturbed concentrations of propionic acid, homocystein and methionine. Whole-exome sequencing identified a de novo, truncating mutation in CDKL5 (NM_003159.2:c.419dupA, p.Asn140Lysfs*8). Targeted sequencing excluded concomitant mutations in methylmalonic academia-associated genes. No methylmalonic acidemia has been reported in children with CDKL5 disorder. Extensive analyses on organic acid metabolism for males with CDKL5 mutations will gain more insight into their biochemical profiles in infancy.     

Curative Resection Following Neoadjuvant Chemotherapy for Advanced Gastric Cancer With Preservation of a Right Gastroepiploic Artery Coronary Artery Bypass Graft: A Case Report

Recently, the right gastroepiploic artery (RGEA) has been used in coronary artery bypass graft (CABG) as an alternative arterial graft. Because of the improvement of prognosis after CABG, malignant diseases are more common in older patients. However, there is a serious problem in patients with gastric cancer after CABG with RGEA graft. In these patients, an interruption of coronary blood supply through the RGEA may cause a life-threatening myocardial ischemia. Therefore, an appropriate strategy is very important to avoid risk while retaining the curability of the operation. We herein describe a 76-year-old Japanese man with advanced gastric cancer who underwent CABG using the RGEA. Abdominal computed tomography (CT) showed #6 lymph nodes (sub-pyloric lymph nodes) metastases surrounding the RGEA. We concluded that curative resection was impossible while preserving the RGEA and started combination chemotherapy using S-1 and cisplatin. After 2 courses of that, #6 lymph nodes were reduced extremely. Thereafter the patient underwent distal gastrectomy with regional lymph node dissection around the RGEA without excision of the RGEA. Histologically, there were no metastases in #6 lymph nodes. Neoadjuvant chemotherapy may be effective for preserving the RGEA graft in a patient with advanced gastric cancer after CABG.Key words: gastric cancer, CABG, RGEA bypass graft, neoadjuvant chemotherapyThe right gastroepiploic artery (RGEA) has been used in coronary artery bypass graft (CABG) surgery.^1,2 It is recognized as a reliable conduit with superior long-term patency.^3–5 The right gastroepiploic artery is mainly targeted to the right coronary artery because of the limitation of its length. According to the report of a Japanese association for coronary artery surgery, CABG was carried out in more than 0.1 million patients over a period of 7 years that ended in 2004, and the RGEA has been used in more than half of these patients.⁶ After CABG for either triple-vessel or left main disease, patients have a 5-year actual survival rate of 92.9% and a cardiac death-free rate of 97.8%.⁷ Long-term survival increases the opportunity for patients to develop malignant diseases. An increased incidence of gastric cancer after CABG with the use of RGEA has been reported.⁶ In these patients, an interruption of coronary blood supply through the RGEA may cause a life-threatening myocardial ischemia. Therefore, an appropriate strategy is required to avoid risk while retaining the curative potential of the operation. We present a case of gastric cancer after CABG with the RGEA in which neoadjuvant chemotherapy led to curative operation while preserving the RGEA.