A glomerular permeability factor produced by human T cell hybridomas

A glomerular permeability factor produced by human T cell hybridomas. T cell hybridomas derived from the T cells of a patient with minimal change nephrotic syndrome (MCNS) made a glomerular permeability factor (GPF). Sufficient quantities of GPF were available for further analysis and characterization. We obtained four stable clones of human T cell hybridomas which produced a glomerular permeability factor. When this factor was injected intravenously into rats, significant proteinurias were induced, and in normal human lymphocyte culture, GPF enhanced Concanavalin-A (Con-A) induced lymphocyte histogenesis by greater than ten fold. GPF was cytotoxic to tumor cell lines of epithelial origin, but only cytostatic to tumor cells of hematopoietic origin. Electron microscopy studies, with polyethyleneimine (PEI) staining, indicated that GPF induced the changes in the arrangement of PEI particles and partial fusion of glomerular epithelial cells in the rats given this factor intravenously. The molecular weight of GPF were estimated to be between 60,000 and 160,000 daltons. The molecular weight of the factor and its TNF like activity, we speculated that the factor was a lymphokine, like lymphotoxins

Development of engineered chromatic acclimation sensor with strict and reverse response to light signal, and application to optogenetic control in cyanobacteria

Genetic regulation and metabolic engineering enabled cyanobacteria to produce renewable chemical compounds from carbon dioxide via photosynthesis. Optogenetic control enables to precisely regulate the timing and level of gene expression without chemical inducer which is environment-hazardous. We recently developed a green-light regulated gene expression system in a model cyanobacterial strain Synechocystis sp. PCC6803 (hereafter PCC6803) [1] and a fast-growing marine cyanobacterial strain Synechococcus sp. NKBG15041c (hereafter NKBG15041c) [2] using a PCC6803-derived chromatic acclimation sensor, CcaS/CcaR two-component system [3]. However, the regulation of gene expression by CcaS is not strictly controllable and the background expression level under non-inductive condition is not negligible. Furthermore, altering the direction of gene expression, that is induction under red-light and repression under green-light, may expand its flexibility as one of the genetic tools. To obtain stricter and versatile system, we fabricated engineered CcaSs focusing on its domain structure using Escherichia coli expression system. One of the engineered CcaSs, CcaS#11, showed reverse response to light signal, i.e. inducible under red-light and strictly repressible under green-light [4]. To investigate the potential application and versatility of CcaS#11 as the red-light regulated gene expression system in cyanobacteria, we next introduced CcaS#11/CcaR two-component system and GFPuv as a probe of gene expression into PCC6803 after knocking out genomic CcaS/CcaR two-component system to exclude the interference. In this strain, the gene expression was induced under red-light and strictly repressed under green-light as we expected. Then, we applied this system to NKBG15041c. Similarly, red-light inducible gene expression with 2-fold higher ON/OFF ratio compared with the original system was successfully observed in NKBG15041c. Remarkably, there was no leaky expression under green-light, indicating that this system enables strict regulation of gene expression by light signal. In conclusion, we successfully constructed the engineered CcaS, CcaS#11, with strict and reverse response to light signal. Then we also confirmed its versatility and applicability as the red-light regulated gene expression system with strict regulation in cyanobacteria. Further development of the light regulated bioprocess will be expected using cyanobacterial hosts with this system, as a cell factory for the renewable chemical compounds production. [1] K. Abe et al., ‘Engineering of a Green-light Inducible Gene Expression System in Synechocystis sp. PCC 6803’, Microb. Biotechnol. 7 (2014) 177-183 [2] A. Badary et al., ‘The Development and Characterization of an Exogenous Green-light-regulated Gene Expression System in Marine Cyanobacteria’, Mar. Biotechnol. 17 (2015) 245-251 [3] Y. Hirose et al., ‘Cyanobacteriochrome CcaS is the Green Light Receptor That Induces the Expression of Phycobilisome Linker Protein’, Proc. Natl. Acad. Sci. USA 105 (2008) 9528-9533 [4] M. Nakajima et al., ‘Construction of a Miniaturized Chromatic Acclimation Sensor from Cyanobacteria with Reversed Response to a Light Signal’, Sci. Rep. 6 (2016) 3759

Production of asari (Manila) clams, Ruditapes philippinarum, during the period of harvest decrease in the 2000s in the Banzu tidal area, Tokyo Bay

In Tokyo Bay, the harvestable quantity of asari (Manila) clams Ruditapes philippinarum has been decreasing since the late 1990s. We conducted a field investigation on clam density in the Banzu culture area from April 1988 to December 2014 and collected records spanning January 1986 to September 2017 from relevant fisheries cooperative associations to clarify the relationship between the temporal variation in stock abundance and the production activities of fishermen. The yearly variation in clam abundance over the study period was marked by larger decreases in the numbers of larger clams. A large quantity of juvenile clams, beyond the biological productivity of the culture area, may have been introduced as seed stock in the late 1980s despite the high level of harvestable stock. The declines in harvested quantity began in the late 1990s and may have been caused by decreases in harvestable stock despite the continuous addition of seed stock clams. The harvested quantity is likely to be significantly dependent upon the wild clam population, even within the culture area, as the harvestable quantity was not correlated with the quantity of seed stock introduced during the study period. These declines in harvested quantity may have resulted from a decreasing number of operating harvesters due to the low level of harvestable stock and consequently reduced profitability. Two findings were emphasized. A certain management style, based on predictions of the contributions of wild and introduced clams to future stock biomass, is essential for economically-feasible culturing. In areas with less harvestable stock, actions should be taken to maintain the incomes of harvesters while avoiding overexploitation, even if the total harvest quantity decreases

Long-term effectiveness of right septal pacing vs. right apical pacing in patients with atrioventricular block

AbstractBackgroundLong-term right ventricular apical (RVA) pacing increases the risk of heart failure (HF) by inducing ventricular dyssynchronization. Although recent studies suggest that right ventricular septal (RVS) pacing results in improved short-term outcomes, its long-term effectiveness remains unclear.Methods and resultsThis study investigated 149 consecutive patients who underwent implantation of a dual chamber pacemaker for atrioventricular block with either RVS-pacing between July 2007 and June 2010 or RVA-pacing between January 2003 and June 2007. The endpoint was defined as death and hospitalization due to heart failure (HF). The rates of mortality and hospitalization due to HF were significantly lower in the RVS-pacing group than that in the RVA-pacing group (event free RVS: 1 year, 98% and 2 years, 98%; RVA: 1 year, 85% and 2 years, 81%; p<0.05). None of the patients died from HF in the RVS-pacing group, while 4 patients died from HF in the RVA-pacing group within 2 years after pacemaker implantation. The paced QRS interval was significantly shorter with RVS pacing than with RVA pacing at different times after pacemaker implantation (RVS: immediately 157.8±24.0ms, after 3 months 157.3±17.5ms, after 6 months 153.6±21.7ms, after 12 months 153.6±19.4ms, after 24 months 149.3±24.0ms vs. RVA: immediately 168.3±23.7ms, after 3 months 168.7±26.0ms, after 6 months 168.0±22.8ms, after 12 months 171.2±22.3ms, after 24 months 176.1±25.5ms; p<0.05).ConclusionsRVS pacing is feasible and safe with more favorable clinical benefits than RVA pacing

Influence of unique layered microstructure on fatigue properties of Ti-48Al-2Cr-2Nb alloys fabricated by electron beam melting

The influence of a unique layered microstructure consisting of duplex-like region and equiaxed γ grain layers (γ bands) on the fatigue properties of Ti-48Al-2Cr-2Nb alloy bars fabricated by electron beam melting (EBM) was investigated at room temperature (RT) and 1023 K focusing on the angle (θ) between the building direction and cylinder (loading) axis. We found for the first time the fatigue strengths of the alloy bars with the layered microstructure depend strongly on the angle θ. Particularly, the fatigue strength of the alloy bars fabricated at θ = 45° is comparable to that of the hot isostatic pressing (HIP) treated cast alloys, even without HIP treatment. We also found the alloy bars fabricated at θ = 0° and 45° exhibit high fatigue strengths in the low-cycle fatigue life region at 1023 K similar to θ = 45° alloy bars at RT. These high fatigue strengths are caused by inhibition of the brittle main crack initiation by stress relaxation due to shear deformation at the γ bands and large plasticity of the alloys. These findings indicate that the alloys fabricated by EBM at θ = 45° with the unique layered microstructure have a great potential for aerospace and automobile applications.Cho K., Kobayashi R., Oh J.Y., et al. Influence of unique layered microstructure on fatigue properties of Ti-48Al-2Cr-2Nb alloys fabricated by electron beam melting. Intermetallics 95, 1 (2018); https://doi.org/https://doi.org/10.1016/j.intermet.2018.01.009

Right Atrial Volume Calculated by Multi-detector Computed Tomography: Useful Predictor of Atrial Fibrillation Recurrence after Pulmonary Vein Catheter Ablation

We investigated whether right atrial (RA) volume could be used to predict the recurrence of atrial fibrillation (AF) after pulmonary vein catheter ablation (CA). We evaluated 65 patients with paroxysmal AF (mean age, 60+10 years, 81.5% male) and normal volunteers (57 ± 14 years, 41.7% male). Sixty-four-slice multi-detector computed tomography was performed for left atrial (LA) and RA volume estimations before CA. The recurrence of AF was assessed for 6 months after the ablation. Both left and right atrial volumes were larger in the AF patients than the normal volunteers (LA: 99.7+33.2ml vs. 59.7+17.4ml; RA: 82.9+35.7ml vs. 43.9+12ml; P100ml) for predicting the recurrence of AF was 81.3% in 13 of 16 patients with AF recurrence, and the specificity was 69.4% in 34 of 49 patients without recurrence. The sensitivity with large RA volumes (>87ml) was 81.3% in 13 of 16 patients with AF recurrence, and the specificity was 75.5% in 37 of 49 patients without recurrence. RA volume is a useful predictor of the recurrence of AF, similar to LA volume

Effect of Implantable Cardioverter-defibrillator Therapy for Ventricular Fibrillation Patients with Out-of-hospital Cardiac Arrest

Survivors of ventricular fibrillation out-of-hospital cardiac arrest（VF-OHCA）due to potentially reversible causes such as acute coronary syndrome（ACS）, vasospastic angina and electrolyte abnormalities are considered low risk for recurrent arrhythmia. Accordingly, implantable cardioverter-defibrillator therapy is not routinely recommended in such patients. We investigated the risk of mortality and the value of ICD therapy for VF-OHCA. Among 2,248 cardiopulmonary arrest patients presenting at our hospital, we retrospectively investigated 110 patients with VF-OHCA who were admitted for treatment. We divided the patients based on ICD（n＝71） or No-ICD status（n＝39）, and on reversible cause（n＝70） or irreversible cause（n＝40）. The groups were compared for baseline characteristics, mortality and ICD therapies. Patients with a reversible cause had a significantly lower rate of ICD implantation than those with an irreversible cause（P＝0.03）. Males in the ICD group presented more frequently than those in the No-ICD group, and cardiac mortality in patients with acute coronary syndrome was significantly lower with ICD therapy than without ICD（P＝0.04）. The rate of appropriate ICD therapies with a reversible cause was 28％, and the first ICD therapy was highest within 1 year post-implantation. Patients with VF-OHCA due to a reversible cause remain at high risk of recurrent ventricular arrhythmias, suggesting that ICD implantation is a reasonable approach in such cases

Head-up Tilt Test May Be Useful for Determining Permission of Flight for Regular Passenger Aircraft Pilots with Vasovagal Syncope

To determine the permissibility of piloting an aircraft with vasovagal syncope （VVS） is a complex responsibility, because it is difficult to evaluate VVS quantitatively. There are no clear guidelines for aircraft pilots with VVS. In some facilities, Head-up Tilt Test （HUTT） is used to determine its reproducibility and treatment effect. In most cases, permission is dependent on the strict examinations by specialists and judgement of the committee established for each country. Therefore, we assessed pilots with VVS and designed an algorism of permission for piloting an aircraft. Here, we describe 7 consecutive regular passenger aircraft pilots with VVS who were restricted to fly. All patients were men and their mean age was 37 years. All pilots were permitted to fly after at least two or more tilt-tests. The observation period was two years after flight permission. None of the pilots in the present study fainted after receiving flight permission. We can make a risk stratification to determine hypotensive susceptibility by multiple tilt tests. Based on the results of multiple HUTT, we can more quantitatively make the judgement as to whether the pilot’s VVS is well managed

An index formula for the degree of (S)+-mappings associated with one-dimensional p-Laplacian

The topological degree for (S)+-mappings concerning a nonlinear eigenvalue problem associated with one-dimensional p-Laplacian is evaluated. The result is applied to a variational inequality, where the multiple existence of solutions is discussed