Pancreatic β Cell–specific Expression of Thioredoxin, an Antioxidative and Antiapoptotic Protein, Prevents Autoimmune and Streptozotocin-induced Diabetes

The cytotoxicity of reactive oxygen intermediates (ROIs) has been implicated in the destruction of pancreatic β cells in insulin-dependent diabetes mellitus (IDDM). Thioredoxin (TRX), a redox (reduction/oxidation)-active protein, has recently been shown to protect cells from oxidative stress and apoptosis. To elucidate the roles of oxidative stress in the development of autoimmune diabetes in vivo, we produced nonobese diabetic transgenic mice that overexpress TRX in their pancreatic β cells. In these transgenic mice, the incidence of diabetes was markedly reduced, whereas the development of insulitis was not prevented. Moreover, induction of diabetes by streptozotocin, an ROI-generating agent, was also attenuated by TRX overexpression in β cells. This is the first direct demonstration that an antioxidative and antiapoptotic protein protects β cells in vivo against both autoimmune and drug-induced diabetes. Our results strongly suggest that oxidative stress plays an essential role in the destruction of β cells by infiltrating inflammatory cells in IDDM

Suzaku Observations of SGR 1900+14 and SGR 1806-20

Spectral and timing studies of Suzaku ToO observations of two SGRs, 1900+14 and 1806-20, are presented. The X-ray quiescent emission spectra were well fitted by a two blackbody function or a blackbody plus a power law model. The non-thermal hard component discovered by INTEGRAL was detected by the PIN diodes and its spectrum was reproduced by the power law model reported by INTEGRAL. The XIS detected periodicity P = 5.1998+/-0.0002 s for SGR 1900+14 and P = 7.6022+/-0.0007 s for SGR 1806-20. The pulsed fraction was related to the burst activity for SGR 1900+14.Comment: 8 pages, 3 figures, Accepted for publication in PASJ (Suzaku 3rd special issue

1-year tolvaptan efficacy in ADPKD

Autosomal dominant polycystic kidney disease (ADPKD) develops into end-stage kidney disease by 65 years of age in an estimated 45%-70% of patients. Recent trials revealed that tolvaptan inhibits disease progression both in early-stage or late-stage ADPKD ; however, stratified analysis showed a difference of favorable factors correlated with tolvaptan efficacy between early-stage and late-stage ADPKD. Thus, we examined the efficacy of tolvaptan in ADPKD with a wide range of estimated glomerular filtration rates (eGFR). We enrolled 24 patients with eGFR 35.3 (28.0-65.5) ml / min / 1.73m2 and evaluated treatment effect as ΔΔeGFR (ml / min / 1.73m2 / year) or ΔΔtotal kidney volume (TKV) (% / year) that was calculated as post-treatment annual change - pre-treatment annual change. Pre ΔeGFR was significantly low in eGFR responders, defined as ΔΔeGFR > 0 ml / min / 1.73m2 / year. In eGFR responders, pre ΔeGFR, post ΔeGFR, eGFR, TKV, and proteinuria were significantly correlated with ΔΔeGFR. In TKV responders defined as ΔΔTKV > 5 % / year, we identified hypertension history, proteinuria, TKV, and post ΔTKV as significantly correlated factors with ΔΔTKV. In conclusion, pre ΔeGFR may be a predictive factor of therapeutic efficacy on kidney function. Tolvaptan may have greater efficacy in early-stage ADPKD with rapid GFR decline or with well-controlled blood pressure

Spectral evolution of GRB 060904A observed with Swift and Suzaku -- Possibility of Inefficient Electron Acceleration

We observed an X-ray afterglow of GRB 060904A with the Swift and Suzaku satellites. We found rapid spectral softening during both the prompt tail phase and the decline phase of an X-ray flare in the BAT and XRT data. The observed spectra were fit by power-law photon indices which rapidly changed from $\Gamma = 1.51^{+0.04}_{-0.03}$ to $\Gamma = 5.30^{+0.69}_{-0.59}$ within a few hundred seconds in the prompt tail. This is one of the steepest X-ray spectra ever observed, making it quite difficult to explain by simple electron acceleration and synchrotron radiation. Then, we applied an alternative spectral fitting using a broken power-law with exponential cutoff (BPEC) model. It is valid to consider the situation that the cutoff energy is equivalent to the synchrotron frequency of the maximum energy electrons in their energy distribution. Since the spectral cutoff appears in the soft X-ray band, we conclude the electron acceleration has been inefficient in the internal shocks of GRB 060904A. These cutoff spectra suddenly disappeared at the transition time from the prompt tail phase to the shallow decay one. After that, typical afterglow spectra with the photon indices of 2.0 are continuously and preciously monitored by both XRT and Suzaku/XIS up to 1 day since the burst trigger time. We could successfully trace the temporal history of two characteristic break energies (peak energy and cutoff energy) and they show the time dependence of $\propto t^{-3} \sim t^{-4}$ while the following afterglow spectra are quite stable. This fact indicates that the emitting material of prompt tail is due to completely different dynamics from the shallow decay component. Therefore we conclude the emission sites of two distinct phenomena obviously differ from each other.Comment: 19 pages, 9 figures, accepted for publication in PASJ (Suzaku 2nd Special Issue

Surgery for postoperative recurrence of gastric cancer

The six patients who underwent reoperation for recurrence of gastric cancer following surgery were clinically analysed, of whom one had lung metastasis and the other five local recurrences. The conditions of resectability are that carcinoma infiltration should be limited, the disease-free interval-after the first operation should be long and there are no blood-borne metastases into the lung and the liver. The surgical outcome for lung metastasis was pessimistic. It is emphasized that multidisciplinary therapy and early detection are indispensable for improving the surgical outcome in the treatment of recurrence of gastric cancer

Limited Resection for Lung Cancer

Based on clinical as well as experimental studies, limited operation of choice was evaluated for the management of lung cancer. From clinical analysis of 39 cases who underwent limited lung resection, our clinical experiences indicated that this operative procedure would be feasible for a large tumors of approximately 4cm in diameter. However, the incidence of lymphnode metastasis is more likely to be high when applied to the tumors of more than 3cm in diameter. The favorable indication, therefore, is for the cancer less than 3cm in diameter. By careful evalution of 7 cases with postoperative recurrence, it has become obvious that either the degree of cell differentiation or the existence of lymph nodes metastasis strongly participate in its prognosis. According to hemodynamic studies immediately after surgery, limited resection of the lung is preferred to conventional radical lobectomy for patients with cardiovascular malfunction because it serves to eliminate a possible left ventricular failure after surgery. An experimental research also demonstrated favorably hemodynamic benifits of limited resection for reducing left ventricular overloading on coronary diseased heart which is experimentally prepared by either creation of stenosis of the main left coronary artery or ligation of the left descending coronary artery. The immune response in the lymphnodes to a tumor growth also was attested in C3H mice with use of MH 134 tumor inoculated, especially in relation to the time of tumor resection. The results of our experiments confirmed that tumor resection on the 7th and 10t

An Experimental Evaluation of Tracheal Blood Flow with Special Referrence to Operative Procedure of Tracheal Mobilization

Based on the study with special referrence to blood flow in the trachea, the factors influential on the operative procedure of tracheal mobilization were carefully evaluated to ensure optimal surgical results. It has already been assumed with an aid of microangiographic technique that the main trancheal blood flow comprise two routes, namely, adventitial and submucosal layers. The amount of blood flow in the trachea divided into individual two layers were measured by hydrogen clearance test with wire electrodes placed in either adventitial or submucosal layer. When employed the procedure of extensive mobilization of the trachea, the level of tracheal blood flow reduced in adventitial layer rather lthan in submucosal layer. Blood flow in submucosal layer, however, remain closely near the normal level, which is thought to compensate a decreased blood supply in the tracheal adventitia. Meanwhile, when proposed an excessive tension of more than 800g at the site of anastomosis, a decrease in submucosal blood flow has become manifest despite of a slight decrease in adventitial blood flow simultaneously. Greater emphasis has been focused upo

Experimental Evaluation of Tumor Inhibitory Effect of Induced Infection on Tumor Growth

To evaluate as to whether coexisting infection is helpful to achieve the tumor regression, the inhibitory effect was experimentally assessed from the view point of survival, the degrees of reticuloendothelial activation (Congo-red clearance test) and immune response (Jerne\u27 plaque forming cell test and macrophage migration inhibition test). A 3×107 to 2×108 of β-streptococcus inoculated in C3H mice of 6 week-old were prepared for producing a varying models of infection. As a control study, survival challenging for a 1X106 of Ehrlich tumor inoculation was surveyed. It averaged 16.6 days, whereas it increased when added infection. The most longest survival was 24.4 days when infection was provoked when a 3×107 β-streptococcus were inoculated subcutaneously 5 days prior to Ehrlich tumor cell implantation. Phagocytic activity in the recticuloendothelial system was found to be consequent of stimulation by the varying variety of infection. To assess the inhibitory effect of induced infection on tumor growth, a directly weighing method was applied for inoculated methylcholantrene tumor at interval of 5 days. It is proved that infection is more effective in depressing tumor growth. Furthermore, our experiment indicated that infection enabled the host to enhance the immune response to various antigen, which might be originated from the reticuloendothelial hyperactivity. As the result of this study, we concluded that a mild and long-standing infection might play a key role in inhibiting tumor growth to some extent

Early Gastric Cancer Presenting Pyloric or Prepyloric Stenosis

Out of 390 patients with early gastric cancer (EGC) who underwent gastric resection between Jan. 1968 and Jul. 1987, four patients developed pyloric stenosis and one patient developed prepyloric stenosis. Macroscopic types of EGC were II c in three cases and II c + III in two cases. Histologic types were tubular adenocarcinoma in four patients, and poorly differentiated adenocarcinoma in one patient. Cancer existed just right on or immediately adjacent to the pyloric ring in all patients; and extended transversely to the gastric axis in four patients, and longitudinally in one patient. An associated open ulcer and/or ulcer scar in the cancer lesion was seen in four patients, and submucosal fibrosis in three patients to a variety of degree, both of which were thought to be greatly attributed to pyloric or prepyloric stenosis. A duodenal ulcer was not present in any patients

In Orbit Timing Calibration of the Hard X-Ray Detector on Board Suzaku

The hard X-ray detector (HXD) on board the X-ray satellite Suzaku is designed to have a good timing capability with a 61 $\mu$s time resolution. In addition to detailed descriptions of the HXD timing system, results of in-orbit timing calibration and performance of the HXD are summarized. The relative accuracy of time measurements of the HXD event was confirmed to have an accuracy of $1.9\times 10^{-9}$ s s$^{-1}$ per day, and the absolute timing was confirmed to be accurate to 360 $\mu$s or better. The results were achieved mainly through observations of the Crab pulsar, including simultaneous ones with RXTE, INTEGRAL, and Swift.Comment: Accepted for publication on PASJ Vol.60, SP-1, 200