Lipoprotein(a) stimulates the proliferation of cultured human arterial smooth muscle cells through two pathways

AbstractWe investigated the effect of lipoprotein(a) (Lp(a)) on proliferation of human arterial smooth muscle cells (SMCs) and its mechanisms of action. Low density lipoprotein (LDL), Lp(a) and apolipoprotein(a) (apo(a)) significantly stimulated the proliferation of SMCs. Lp(a) and apo(a) reduced the amount of active transforming growth factor-β (TGF-β) with the mink lung epithelial cell bioassay, however LDL had no effect. Lp(a), but not apo(a), significantly stimulated the proliferation of SMCs even in the presence of a neutralizing antibody for TGF-β. Our results suggest that Lp(a) stimulates the proliferation of SMCs via apo(a)-induced inhibition of TGF-β activation and stimulation of SMCs by the LDL-particle of Lp(a)

Evaluation of Myelotoxicity in Dietary Restricted Rats

The purpose of this study was to clarify the effect of decreased food consumption on evaluation of myelotoxicity in routine general toxicity studies. Male rats were divided into the following 7 groups: 12, 15, and 18 mg/kg 5-fluorouracil (5-FU) treatment groups (FU12, FU15 and FU18); dietary restriction groups (R12, R15 and R18 receiving the same amount of food as the rats in the FU12, FU15 and FU18 groups, respectively); and a nontreated control group (NT). We compared the changes in body weight, hematology and the results of cytological analyses of bone marrow and histopathology among the groups after administration and recovery periods of 14 and 7 days, respectively. At the end of the administration period, the FU15 and FU18 groups showed decreases in many hematologic and bone marrow parameters that were all similar to those in the corresponding dietary restriction groups (R15 and R18). A granulocyte abnormality (polyploidy: frequency of 1% or less) was also observed in all 5-FU treated groups. At the end of the recovery period, increases in the reticulocyte and platelet counts and extramedullary hematopoiesis of the spleen were observed in the 5-FU treated groups. These results indicate that the results of general toxicity studies in rats should be evaluated in consideration of dietary restriction effects when food consumption is decreased at about 30-40% or more. Careful morphological observation of hemocytes would be helpful in distinguishing the effect of a drug from that of dietary restriction in relation to hematological and bone marrow parameters. Performance of a recovery test to determine the reactive response of hematopoiesis is also recommended

Quality Measurement of Two Phase Flow with Plug Flow

In order to control refrigeration cycles employing an injection system properly, it is important to detect quality of gas–liquid two-phase refrigerant in a two-phase region of the cycle. Although there are some techniques such as using a capacitance sensor or a X-ray beam scanning to measure a cross-sectional void fraction of the gas-liquid two-phase flow in a pipe, the measurement of the quality or flow rate of each phase is quite difficult since the liquid phase and gas phase of two-phase flow flowing in a pipe have different velocities in most cases. Meanwhile, the flow through a narrow tube becomes plug flow and the velocities of gas plug and liquid plug are almost the same. Therefore, the void fraction or quality of two-phase flow with plug flow in the narrow tube can be measured by detecting each plug length. Authors have examined the quality measurement of two-phase flow in the refrigeration cycle based on the plug flow characteristics. In previous studies, it was confirmed that the quality can be measured with an accuracy of about ±10% when the flow regime is plug flow in the narrow tube. However, the quality range where the flow regime becomes the plug flow is limited to the quality less than 0.1. In this study, multiple narrow tubes are installed with a gas bypass line to extend the quality range to be measured. Consequently, the measurable range of quality up to 0.8 was achieved with an accuracy of ±10%

Importance of Starting Age for Myelotoxicity Study in Dietary Restricted Rats

The aim of this study was to prove our hypothesis that adult rats with lowering of body weight gain, rats at 12 weeks of age as an example, are suitable for evaluation of myelotoxicity. Age-related differences between young rats (6-week-old study) and adult rats (12-week-old study) were analyzed in hematological examination values. The data of the young rats were reprinted from our previous report (Miyata et al., 2009) since our hypothesis was verified by comparison with that previous report. Several experimental groups were defined for the 12-week-old study as well as for the 6-week-old study; these included 5-fluorouracil (5-FU) treated groups receiving 12, 15 and 18 mg/kg/day (FU12, FU15 and FU18), pair-feeding groups (R12, R15 and R18 receiving the same amount of food as in the FU12, FU15 and FU18 groups, respectively) and a nontreated control group. Numerous hematologic and bone marrow parameters in the 5-FU treated groups were comparable to those in the corresponding pair-feeding groups in both age studies. Generally, the influences of undernutrition were more apparent in the young rats than in the adult rats. Histopathological examinations showed a decrease in hematopoiesis in the bone marrow in the 5-FU treated and pair-feeding groups. No apparent differences were observed in the decreased hematopoiesis between the 5-FU treated and pair-feeding groups in the 6-week-old study, but a difference between these groups was noted in the 12-week-old study; decreased hematopoiesis was more frequently noted in the 5-FU treated groups. These facts suggest that adult rats are more suitable than young rats for evaluation of 5-FU-induced myelotoxicity

Evaluation of Short-term Myelotoxicity Study in Dietary Reduced Rats

This study attempted to prove our hypothesis that a short-term toxicity study, using a 4-day dosing regimen as an example, is suitable for evaluating myelotoxicity in rats. We compared the hematological, bone marrow cytological and histopathological results of 5-fluorouracil (5-FU) treated and pair-feeding groups after a 4-day administration period. Several experimental groups were defined for this 4-day study as well as for our previously reported 14-day study (Miyata et al., 2009); these included 5-FU treated groups receiving 12, 15 and 18 mg/kg/day (FU12, FU15 and FU18), pair-feeding groups (R12, R15 and R18 receiving the same amount of food as the FU12, FU15 and FU18 groups, respectively) and a nontreated control group. Although severe reductions in body weight gain and food consumption were reported in the 14-day study, only slight reductions were observed in the 4-day study. In the 4-day study, a decrease in blood reticulocytes and a decreasing trend of marrow erythroid cells were only observed in the FU18 group, and no effects were observed in the pair-feeding groups. The erythroblastic changes observed in this 4-day study were thought to reflect the direct influence of 5-FU administration. Since concerns regarding the influence of secondary changes related to undernutrition were minimized in the 4-day study, it was thought to clarify the direct influence of 5-FU administration on erythroblastic cells. Thus, a 4-day study protocol might be helpful for distinguishing secondary changes related to undernutrition

AN OPTIMIZATION-BASED APPROACH FOR GRASP POSTURE GENERATION OF DIGITAL HAND

ABSTRACT * Recently, as handheld information appliances, such as mobile phones, PDAs, have widely spread, the development of these appliances should pay more attention in their ergonomic design. However, the user tests for developing the "ergonomic" appliances are usually done by many real subjects testing a variety of these physical mockups, and the process of these tests usually requires the expensive cost and has to take a long time. So, we propose a software system of an automatic ergonomic assessment system for designing handheld information appliances by integrating the digital hand model with the 3D product model of the appliance. Our system has the following four feature functions for ergonomic assessment: 1) Generation of kinematically and geometrically accurate digital hand models with rich dimensional variation, 2) automatic grasp posture generation and evaluation of the posture stability by estimating the force-closure and the grasp quality, 3) automatic evaluation of ease of the finger motion in operating the user interface, 4) aiding the designers to re-design the housing shapes and user-interfaces in the product model. In this paper we propose a new optimization-based method the 2) of the above functions. As the objective function, we use the number of the contact points, the fit of the specific part of the hand surface for the feature edges of the product surface and the margin for the constraints on the joint angle limits of the figures. The experimental studies on the grasp posture generation for the digital camera indicate that more realistic grasp posture could be generated using the proposed * N14 W9, Kita-ku, Sapporo, Hokkaido 060-0814, Japan. Email: [email protected] optimization-based method than the one using our former method