This study was conducted on the Fukushima Medical University (FMU) premises (in Fukushima City, Fukushima Prefecture) about four years after the Fukushima Daiichi Nuclear Power Plant accident. Its objectives were (1) to create a map of the ambient gamma dose rate (air-kerma rate) distribution, (2) to evaluate the air-kerma rate originating from natural radionuclides, and (3) to investigate the effects of snow cover on changes in the air-kerma rate. This man-borne survey revealed that the air-kerma rate varies widely, ranging from 0.038 μGy h－1 to 0.520 μGy h－1, and is higher on grass than on the other investigated surface types, such as soil, asphalt, and bricks. In this area, the mean air-kerma rate from natural radiation was evaluated to be 0.03 ± 0.01 μGy h－1, which is close to 0.04 μGy h－1, which was measured in central Fukushima City by a local authority.Furthermore, snowfall was found to reduce the air-kerma rate by 5%-30%. This reduction was attributed to attenuation of the primary radiation while passing through the snow cover, and the measured contribution of scattered radiation to the air-kerma rate reduction was small. The reduction rate was found to depend on the initial snow depth but to maintain a similar value for a couple of days, after the snow had partially melted and its depth had decreased. Finally, analysis of the daily dose due to external exposure received on the FMU premises revealed that no further health effects due to chronic radiation exposure at this site are to be expected.
Using the perforated patch voltage clamp, we investigated swelling-activated ionic channels (SACs) in rat urinary bladder smooth muscle cells. Hypo-osmotic (60%) bath solution increased a membrane current which was inhibited by the SAC inhibitor, gadolinium. The reversal potential of the hypotonicity-induced current shifted in the positive direction by increasing external K+ concentration. The hypotonicity-induced current was inhibited by extracellular acidic pH, phorbol ester and forskolin. These pharmacological properties are identical to those of arachidonic acid-induced current present in these cells, suggesting the presence of TREK-1, a four-transmembrane two pore domain K+ channel. Using RT-PCR we screened rat bladder smooth muscles and cerebellum for expression of TREK-1, TREK-2 and TRAAK mRNAs. Only TREK-1 mRNA was expressed in the bladder, while all three were expressed in the cerebellum. We conclude that a mechanosensitive K+ channel is present in rat bladder myocytes, which is activated by arachidonic acid and most likely is TREK-1. This K+ channel may have an important role in the regulation of bladder smooth muscle tone during urine storage.
We compared the effects of lysophosphatidylcholine (LPC) and acetylcholine (ACh) on IK(ACh), ICa and a non-selective cation current (INSC) in guinea-pig atrial myocytes to clarify whether LPC and ACh activate similar Gi/o-coupled effector systems. IK(ACh), ICa and INSC were analyzed in single atrial myocytes by the whole cell patch-clamp. LPC induced INSC in a concentration-dependent manner in atrial cells. ACh activated IK(ACh), but failed to evoke INSC. LPC also activated IK(ACh) but with significantly less potency than ACh. The effects of both ligands on IK(ACh) were inhibited by intracellular loading of pre-activated PTX. This treatment also inhibited LPC-induced INSC, indicating that IK(ACh) and INSC induced by LPC are both mediated by Gi/o. LPC and ACh had similar potencies in inhibiting ICa, which was pre-augmented by forskolin, indicating that LPC and ACh activate similar amounts of α-subunits of Gi/o. The different effects of LPC and ACh on IK(ACh) and INSC may suggest that LPC and ACh activate Gi/o having different types of βγ subunits, and that LPC-induced INSC may be mediated by βγ subunits of Gi/o, which are less effective in inducing IK(ACh).
The UL41 gene of herpes simplex virus type 1 (HSV-1) encodes a virion host shut off protein which is involved in immune evasion. The growth and virulence of HSV-1 is markedly reduced by the deletion of UL41. In this report, the UL41-deleted recombinant HSV-1 strain VR∆41 was evaluated as a prophylactic live attenuated vaccine against lethal HSV-1 infection in a mouse model. Intraperitoneal (i.p.) inoculation with the VR∆41 strain clearly inhibited lethal wild-type HSV-1 (VR-3 strain) infection after both i.p. and intracerebral (i.c.) inoculations. Vaccination with the VR∆41 strain was safer than VR-3 vaccination and was able to protect against a wild-type challenge to the same degree as VR-3 vaccination. In contrast, i.p. inoculation with ultraviolet-irradiated VR-3 induced resistance against i.p. infection, but not against i.c. infection. Although replication of the VR∆41 strain in mice was greatly reduced compared to that of the VR-3 strain, VR∆41 strain maintained the ability to spread to the central nervous system (CNS) from a peripheral inoculation site. These results indicated that the VR∆41 strain evoked a potent immune reaction through viral protein expression within CNS without the induction of lethal encephalitis. The entry of antigens into the CNS was essential for the establishment of protective immunity against the lethal HSV encephalitis. We concluded that only a live attenuated vaccine is able to afford a prophylactic effect against CNS infection with HSV. In order to fulfill this requirement, UL41-deleted viruses provide a strong candidate for use as a recombinant live vaccine.
AIM: To investigate the feasibility of endoscopic submucosal dissection (ESD) using sodium carboxymethylcellulose (SCMC) for gastric cancer. METHODS:During October 2011 through April 2013, 98 lesions from 98 patients who underwent ESD using SCMC (ESD-SCMC) for early gastric cancer were enrolled in this study. Two endoscopists, who had each performed fewer than 30 ESD procedures (less-experienced ESD physicians), performed ESD-SCMC under the supervision of two experts. The primary outcome was the enbloc resection rate. Secondary outcomes included the complete resection rate, the procedural time, the bleeding rate after SCMC injection, and complications. Patient characteristics, time necessary for hemostasis after SCMC injection, rate of treatment completion by less-experienced ESD physicians alone, and the effects of SCMC during ESD and on resected specimens were also evaluated. RESULTS:The enbloc resection rate was 100%. Among these resections, 87.8% of the cases were completed by a less-experienced ESD physician alone. The complete resection rate was 98.0%. The mean total procedural time was 75.4 min. The mean incidence of intraoperative bleeding following SCMC local injection was 1.7 times. No bleeding was observed after SCMC injection in 29.6% of cases (29/98). Five complications occurred: one case of microperforation (1.0%) and four cases of postoperative bleeding (4.0%). SCMC remained in the submucosa. The submucosa was readily manipulated when the deep submucosa was dissected, even after placing the specimen on a slide. CONCLUSION:ESD-SCMC is feasible for the resection of early gastric cancer.
We conducted a case series study to assess intracerebral hemorrhage (ICH) in the context of anti-platelets agents (APAs) and platelet (PLT) transfusion in Fukushima Prefecture. This study included patients who were newly diagnosed with ICH between January 2008 and June 2014 in the neurosurgical hospitals of Fukushima Prefecture. Four of ten neurosurgical hospitals responded to our questionnaire. Of 287 ICH patients, 51 (20.6%) were on APA therapy, of whom PLT transfusion was given to only one persistently bleeding patient who was on dual anti-platelet therapy. In a follow-up survey, 30 out of 51 ICH patients on APA therapy, average age 75 years, were analyzed, of whom 21 (70%) were male. The predominant underlying disease was diabetes mellitus. It is interesting to note that peripheral artery disease and aortic aneurysm were among the indications for APAs. ICH was mainly observed supratentorially. Hematoma enlargement was observed in 13 (44.8%) cases. By day 7, 3 patients (10%) had died from complications of ICH. In this study, we show that ICH during APA therapy matched what was observed in Kanagawa Prefecture. Whether or not a national survey differs, we anticipate greater statistical validity and an opportunity to improve patient outcomes in Japan and around the world.
To elucidate the association between the lymphangiogenesis and clinicopathological factors including the survival in breast cancer, 91 Japanese patients with breast cancer were investigated. The lymphangiogenesis was evaluated by the count of lymph vessel density (LVD) with immunohistochemical method using D2-40 monoclonal antibody, a specific marker for lymphatic endothelial cells. D2-40-positive lymph vessels were detected in 87 of 91 cases, and were mainly distributed in the peritumoral lesions or around the tumor edge. There was a significant difference in disease-free survival (DFS) and overall survival (OS) between patients with high LVD and with low LVD (p=0.02, 0.01, respectively, log-rank test). In addition, LVD significantly correlated with the following clinicopathological factors: menopausal status (p<0.01), tumor size (p<0.01), lymph-node status (p=0.01) lymphatic vessel invasion (LVI) (p<0.01), blood vessel invasion (BVI) (p=0.03) and estrogen receptor status (ER) (p=0.02). Those data suggest that D2-40 monoclonal antibody is a useful marker for evaluating the LVD and its evaluation is helpful to predict the survival in breast cancer.
Symptomatic thoracic disc herniation is clinically rare. There are few cases of disc herniation of the thoracic spine in top athletes described in the literature. We herein present a rare case of chest wall pain due to thoracic disc herniation in a professional baseball pitcher. A 30-year-old, left-handed pitcher complained of left-sided chest wall pain in the region of his lower ribs during a game. Neurological examination revealed hypoesthesia of the left side of the chest at the level of the lower thoracic spine. Magnetic resonance imaging (MRI) of the thoracic spine showed a left-sided paramedian disc herniation at the T9-T10 level. The player was initially prescribed rest, administration of pregabalin (150 mg twice a day), and subsequent physical rehabilitation. He was able to resume full training and pitching without medication 6 months after the onset. A follow-up MRI of the thoracic spine showed a reduction in the size of the herniated disc compared to the initial findings. Though relatively rare, thoracic disc herniation should be considered in cases of chest wall pain in athletes.
Immunoglobulin A nephropathy (IgAN) is the most common form of chronic glomerulonephritis worldwide. In Japan, the treatment for use as an initial therapy was established in Guidelines for the Treatment of Childhood IgA nephropathy; however, no rescue therapy for recurrent or steroid-resistant pediatric IgAN was established. We report here a 15-year-old boy with severe IgAN, who was treated with combination therapy involving prednisolone, mizoribine, warfarin, and dilazep dihydrochloride for 2 years. The response to the combination therapy was good and both proteinuria and hematuria disappeared. The pathological findings at the second renal biopsy were improved and PSL was discontinued. However, due to nonadherence to the treatment regimen and tonsillitis, macrohematuria and an increase of proteinuria were again observed and the pathological findings at the third renal biopsy showed clear deterioration. The patient was, therefore, diagnosed with recurrent IgAN. Tonsillectomy plus methylprednisolone pulse therapy (TMP) was performed as a rescue therapy for the recurrence of severe IgAN. Both the proteinuria or hematuria subsequently disappeared, and no proteinuria or hematuria has been observed and kidney function has remained normal during a 5-year follow-up. The patient experienced no severe side effects associated with the drug regimens. In conclusion, our case suggests that TMP may be an effective and useful rescue therapy for recurrent IgAN after multi-drug combination therapy.