Role of Astrocyte Network in Edema after Juvenile Traumatic Brain Injury

Juvenile traumatic brain injury (jTBI) is the leading cause of death and disability in young children and adolescents. Despite its lasting detrimental effects on the developing brain, no pharmacological treatment exists. One of the pathological hallmarks of jTBI is edema. Astrocytes play a key role in the edema process, and have been hypothesized that numerous astrocyte networks allow communication and propagation of edema and secondary injury spread. Two key astrocyte proteins are hypothesized to have a central role in the edema process: Aquaporin 4 (AQP4) and Connexin 43 (Cx43). AQP4 is expressed extensively in astrocyte endfeet, which surrounds the blood vessels as part of the blood brain barrier (BBB). Cx43 is central in astrocyte to astrocyte connection and communication. We hypothesized that AQP4 acted as one of the potential passageway of water into the astrocyte, whereas Cx43 acted as the bridge between astrocytes once inside the brain. By blocking these strategically located pathways, we hypothesized that edema would decrease post-jTBI. In order to achieve specific inhibitions of APQ4 or Cx43, we utilized small interference RNA (siRNA), which is also an endogenous mechanism. We observed that after jTBI both AQP4 and Cx43 was significantly upregulated, edema was prominent, and reactive astrogliosis occurred. When siAQP4 was administered after jTBI, there was functional improvement, decreased edema, and decreased reactive astrogliosis. When siCx43 was administered, there was functional improvement and decreased reactive astrogliosis, but the level of edema did not change. From these findings, it can be seen that (1) AQP4 and Cx43 are upregulated acutely after jTBI, (2) both siAQP4 and siCx43 have therapeutic potentials after jTBI leading to functional recovery, (3) although both target astrocyte endfeet proteins, the mechanism of action seem to be different and AQP4 may play a more direct role in the edema process than Cx43. Future studies could focus on (1) a more clinically relevant delivery of siRNA for jTBI, (2) elucidating the mechanism behind functional improvement of siCx43, and (3) the relationship between AQP4 and Cx43 regarding astrocyte pathology after jTBI

Studies on Economical Meaning of Mechanization of Agriculture. : III. On effects of Mechanization and Farm Size on Working Processes of Rice Production.

One of the biggest changes of agriculture in Japan after the war, has been the mechanization of farm operations. Several kinds of small tillers, worked by kerosene engine, have gradually become popular implements of our farms. Therefore, the present writer wants to analize the changes of labor management that appears to be influenced by the mechanization. But it was difficult to take out the pure effects of machines out of the actual farm managements, for they are the farthest from being able to be treated in the laboratory experiment. When we come to survey the actual farm managements, we often come across the phenomena in which the effects of many factors are intertwined. We can not differenciate them clearly. Then, we asked the Okayama Statistical Office of Agriculture and Forestry Department to allow us to use the basic data for the survey of rice production cost. Even though the data are not always suitable for our purpose, they seem to be the best that are available. Rearranging this basic data for our purpose, we could classify the surveyed farms into three groups which are selected throughout the Okayama Prefecture. According to this classification, there are three types of farm groups; the first (A, A1 and A2) is the large scale farms which are possesed of a small tiller, the second (B, B1 and B2) is the small scale farms which are not possesed of a small tiller but hire it; and the third (C, C1 and C2) is the small or medium scale farms which neither are possesed of nor hire a small tiller. Analyzing the differences among these farm groups, we can find the following trends. (See table 1-7) 1) Speaking on the differences of farm scale among three groups, A groups (A, A1 and A2) are larger than any other groups. 2) Speaking on the differences of commercial crops production among three groups, A groups are most devoted to them and the farms of B groups (B, B1 and B2) are usually the part-time ones. 3) As far as total. working hour for rice production per unit area is concerned, A groups are the least one of these three groups but the differences of working hour among them are relatively slight. 4) The working hour of woman as a family member is shorter in A groups than in other groups. The working hour of hired men, however, is longer in A groups than in other groups. It seems to express that the changes of operater's role in family farm have been affected by mechanization. 5) It is certain that the farms of A groups have the convenient machines and save their labor, but only a few kinds of operations for rice production are practiced by mechanical method and most parts of this operations are practiced by hand method. Therefore, even the farmers of A groups still have to do many hand work for his farm management and sometimes they devote intensive hand practice to their rice production

Studies on Economic Meaning of Agricultural Mechanization. : II. On Productivity of Agricultural Machine.

The major objective of this study was to explore the economic usefullness of agricultural machine. For this objective, it seems reasonable that, to begine with, the specific feature of family farm should be defined. Family farm is a complete economic unit by itself in which business and household are interwined with production and consumption. Although farm management has been mentioned as a unit of firm-business, it has not been an independent unit but an interdependent unit. On the interdependence between a business firm and a consuming household, Dr E. O. Heady and his collaborators have represented excellent works. It is their fundamental view that the family farm pursues as a final goal a high level of living and a maximum satisfaction for family. On grounds of their theories, the writer hopes to analyse the effect of mechanization on the farmer's living. In fig. 4～6, the writer has indicated monetary income and consumption on the vertical axis, and non-monetary income and consumption on the horizontal axis. The curve mn means the production opportunity with limited resources and unchanged farming. The curve ID stands for the consumer indifference curves which illastrate individual's preference between monetary and non-monetary income at one point in time. Thus, the results obtained are summerised as follows: (1) When monetary income is decreased by the effect of mechanization, it does not necessary follow that the satisfaction of farm family decreases. If added non-monetary income is more than enonuh to compensate the loss of amount of money income, the farm family naturally obtain more satisfaction than before. (See fig. 4) (2) When monetary income is unchanged after mechanization occured, satisfaction of family will increase. (See fig. 5) (3) When monetary income is increased by the effect of mechanization, the satisfaction of family will increase. But the satisfaction of family will decrease, if excessive intensification or over-diversified farming sacrifice more non-monetary income than expected to the added money income. (See fig. 6) After the war, agricultural mechanization in Japan has developed rapidly. We can more easily understand the cause of this developement from our theory. In the study of the productivity of agricultural machine, it may be necessary to analyse this problem not only from the aspect of firm business but also from the aspect of firm-household interdependency

Role of Sulfated O-Glycans Expressed by High Endothelial Venule-Like Vessels in Pathogenesis of Chronic Inflammatory Gastrointestinal Diseases

Lymphocyte homing is mediated by a cascade of adhesive interactions between circulating lymphocytes and specialized endothelial cells comprising high endothelial venules (HEVs). Sulfated O-glycans expressed on HEVs, collectively called peripheral lymph node addressin (PNAd), interact with L-selectin expressed on lymphocytes, contributing to the initial step of the lymphocyte homing. In chronic inflammatory states, PNAd is induced on HEV-like vessels but absent in non-lymphoid tissues under normal conditions. Such HEV-like vessels have been observed in various chronic inflammatory diseases including rheumatoid arthritis, lymphocytic thyroiditis, Helicobacter pylori-associated chronic gastritis, and inflammatory bowel disease (IBD), and implicated in lymphocyte recruitment in those diseases. In H. pylori-associated chronic gastritis, PNAd-expressing HEV-like vessels are induced, and the progression of chronic inflammation is highly correlated with appearance of these vessels. Furthermore, eradication of H. pylori by antibiotics resulted in disappearance of PNAd. These results indicate that inhibition of PNAd formation could have therapeutic effect by attenuating lymphocyte recruitment. In ulcerative colitis (UC), PNAd-expressing HEV-like vessels are induced, preferentially in the active phase, and T cells, particularly CD4(+) T cells, are closely associated with these vessels, suggesting that T cell recruitment via PNAd-expressing HEV-like vessels plays at least a partial role in UC pathogenesis. Additionally, N-acetylglucosamine-6-O-sulfotransferase I (GlcNAc6ST-1) is suggested to be a candidate to regulate PNAd induction on HEV-like vessels in UC. These results provide a potential therapeutic strategy to treat UC by blocking T cell adhesion to PNAd-expressing HEV-like vessels. Inhibition or down-regulation of GlcNAc6ST-1 may be an alternative.ArticleBIOLOGICAL & PHARMACEUTICAL BULLETIN. 32(5):774-779 (2009)journal articl

Studies on Economical Meaning of Machanization of Agriculture. : 4. On the Factors Effecting the Labor Hour Spent in Agricultural Production. (part 1)

According to the official survey, the working hour for rice production per unit area is quite different in every farm management. This is because various factors of farm management are effecting the work processes of rice production. From the view point of our studies, these factors can be classified into two groups: one of them is the economic conditions surrounding the outside of farm management and the other is the inside conditions of farm management. Therefore, this report will be limitted only to the analysis of the latter conditions, especially of the next three, i.e., farm scale, field situation (parcellment of fields) and construction of family. As a matter of fact, our effort is devoted to clearing up of the relationship between working hour for rice production per unit area and the above mentioned three factors effecting the labor use. Our results obtained from the same basic data that were utilized in previous report, are as follows: 1) The more the area of cultivated land per farm increases, the more the working hour for rice production per unit area is decreases. More over when the area of cultivated land in above relationship is calculated by the area of one working man, this relationship becomes clearer. 2) The more the number of field lots or plots per farm increases, the more the working hour for rice production per unit area becomes longer. But, if we adopt the number of field lots or plots per unit area in above relationship instead of that per farm, this relationship becomes more proportionate. 3) It is also proved that the same relationship is existing, between the working hour per unit area for rice production and the number of family member per farm that is to say, the increase of working hour is partly caused by the increasing of working Persons of the farm which results the rising of labor input per unit area for rice production. These results seem to express not only the special feature of family farm, but also of Asiatic small farm. Thus, it becomes very important to apply these results for "labor simplification" in our small family farm

Nonlinear Compensation of Two-Dimensional Contouring Servomechanism

This paper gives a method of nonlinear compensation for a two-dimensional contouring servomechanism, by which the cornering error, or the transient error at the corner of a figure being traced, is held within given tolerance. The effect of compensation is analyzed by graphical means, using the result of model experiment and the parameters are determined so as to obtain the desirable performance. Stability analysis of the system is also given utilizing the describing function method. The result is applied to an actual automatic flame cutting machine and the practicability is proved

Analysis of the High-Speed Servo-System with an SCR Servo-Amplifier

In this paper we will analyze the high-speed servo-system with an SCR servo-amplifier. The improvement of the system performance is made by stabilizing the system and obtaining a fast response. For these purposes, two nonlinear compensation networks, a nonlinear lowpass filter and a nonlinear compensation with a Zenor diode, are inserted into the feedback loop. The effects of such compensations are investigated by the model experiments and are discussed, considering them as a nonlinear gain adjustment

Efficacy and safety of amrubicin hydrochloride for treatment of relapsed small cell lung cancer

Long-term survival is quite uncommon in refractory small cell lung cancer (SCLC) patients, with less than 25% of patients with limited-stage disease and 1%–2% of patients with extensive-stage disease remaining alive at five years. Recent clinical studies have demonstrated the promising efficacy of amrubicin for patients with relapsed SCLC. This review presents the results of clinical studies showing the efficacy and safety of amrubicin for the treatment of relapsed SCLC. Amrubicin is a synthetic anthracycline agent with a similar structure to doxorubicin, in which the hydroxyl group at position 9 in amrubicin is replaced by an amino group to enhance efficacy. It is converted to an active metabolite, amrubicinol, which is 5–54 times more active than amrubicin. Amrubicin and amrubicinol are inhibitors of DNA topoisomerase II, exerting their cytotoxic effects by stabilizing a topoisomerase II-mediated cleavable complex. The toxicity of amrubicin is similar to that of doxorubicin, although amrubicin shows almost no cardiotoxicity. In the relevant trials, amrubicin was administered intravenously at a dose of 35–40 mg/m2 on days 1–3 every three weeks. The response rate was 34%–52% and median survival times were 8.1–12.0 months. Common hematologic toxicities included neutropenia, leucopenia, anemia, thrombocytopenia, and febrile neutropenia. Nonhematologic adverse events included Grade 3–4 anorexia, asthenia, hyponatremia, and nausea. The results of the studies which demonstrated the efficacy of monotherapy for relapsed SCLC involved mainly Japanese patients. Therefore, it is necessary to conduct more clinical studies in non-Japanese patients to confirm the efficacy of amrubicin