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Adenosine monophosphate–activated protein kinase (AMPK) is a sensor for cellular energy status. When the cellular energy level is decreased, AMPK is activated and functions to suppress energy-consuming processes, including protein synthesis. Recently, AMPK has received attention as an attractive molecular target for cancer therapy. Several studies have revealed that the activation of AMPK by chemical stimulators, such as metformin, induces apoptosis in a variety of hematologic malignant cells. From another perspective, these results suggest that the function of AMPK is impaired in hematologic tumor cells. However, the precise mechanisms by which this impairment occurs are not well understood. In melanoma cells, oncogenic BRAF constitutively activates the extracellular signal-regulated kinase (ERK) pathway and phosphorylates liver kinase B1, an upstream activator of 5′ adenosine monophosphate–activated protein kinase (AMPK), resulting in the inactivation of liver kinase B1 and AMPK. In this study, we analyzed whether ERK is involved in the suppression of AMPK activity using established and primary human leukemia cells. We found an inverse correlation between the intensity of ERK activity and the degree of AMPK activation after stimulation with either glucose deprivation or metformin. We also found that the inhibition of ERK activity by U0126 restored AMPK activation after metformin treatment. Furthermore, a combined treatment with metformin and U0126 enhanced the antileukemic activity of metformin. Importantly, metformin induced ERK activation by suppressing the protein levels of dual specificity phosphatase 6, a negative regulator of ERK. This crosstalk between AMPK and ERK could diminish the antileukemic activity of metformin. Taken together, our present observations suggest a novel therapeutic strategy for improving the efficacy of metformin in treating leukemia. more...

A three-dimensional $\pm J$ XY spin-glass model is investigated by a nonequilibrium relaxation method. We have introduced a new criterion for the finite-time scaling analysis. A transition temperature is obtained by a crossing point of obtained data. The scaling analysis on the relaxation functions of the spin-glass susceptibility and the chiral-glass susceptibility shows that both transitions occur simultaneously. The result is checked by relaxation functions of the Binder parameters and the glass correlation lengths of the spin and the chirality. Every result is consistent if we consider that the transition is driven by the spin degrees of freedom. more...

We point out a possibility of the weak universality of spin-glass phase transitions in three dimensions. The Ising, the XY, and the Heisenberg models with ±J bond distributions undergo finite-temperature phase transitions with a ratio of critical exponents γ/ν= 2.4. Evaluated critical exponents agree with corresponding experimental results. The analyses are based upon the nonequilibrium relaxation from the paramagnetic state and the finite-time scaling. more...

We find a possibility of a weak universality of spin-glass phase transitions in three-dimensional $\pm J$ models. The Ising, the XY and the Heisenberg models seem to undergo finite-temperature phase transitions with a ratio of the critical exponents $\gamma/\nu \sim 2.4$. Evaluated critical exponents may explain corresponding experimental results. The analyses are based upon nonequilibrium relaxation from a paramagnetic state and finite-time scaling., Comment: 14 pages, 7 figures, manuscript revised, incorrect data are withdrawn more...

The effect of sucrose concentration in the medium on the growth and resumption ability to form lateral roots was investigated using the hairy roots of pak-bung and tobacco. It was found that the growth evaluated by root tip elongation of pak-bung and tobacco hairy roots was suppressed in the medium having an initial sucrose concentration of 3 , and that the resumption abilities of both the hairy roots could be preserved when the hairy roots were kept at an initial sucrose concentration of 2.5 kg/m 3 under ambient temperature conditions. The values of maintenance energy for pak-bung and tobacco hairy roots were determined to be 0.11 and 0.12 per day, respectively, from the total sugar consumption rates. Under the oligotrophic condition of the sucrose concentration of 2.5 kg/m 3 , the hairy roots were considered to exist as resting cells with maintenance metabolism, and the minimum demand for the energy source to ensure survival of the cells was met because the cells hardly multiplied and sugar consumption was not significant. In addition, long-term storage of pak-bung hairy roots in the liquid medium with 2.5 kg/m 3 sucrose was performed at 25°C. It was demonstrated that the hairy roots could maintain their resumption abilities without a serious loss of viability over 600 days and that the number of budding lateral roots per unit length of the main roots remained a value of 72 roots/m after the 600-day storage. more...

To clarify the relationship between the dispersed reverse characteristics of 4H-SiC junction barrier Schottky (JBS) diodes and defects, we investigated the sensitivity of the reverse characteristics to surface and crystalline defects in 4H-SiC epitaxial layers. Strong correlations were obtained between the reverse characteristics of 4H-SiC JBS diodes and surface defects. Micropipes or particles reduced blocking voltage and carrot defects increased leakage current. Furthermore, the leakage current of 4H-SiC JBS diodes depends on the etch pit density of threading dislocations (TDs). Etch pits formed from TDs increased leakage current by about 10-9 A in samples without surface defects. In addition, hexagonal etch pits formed from unusual crystalline defects were observed; they also increased leakage current. more...

The present study was undertaken to examine lead-ethanol interaction with respect to previously reported lead enhancement of urinary Na+ excretion [Y. Suketa, S. Hasegawa and T. Yamamoto, Toxic. appl. Pharmac.47, 203 (1980)]. Simultaneous administration of ethanol reduced the enhancement due to lead alone. A decrease in serum Na+ concentration followed lead administration and the decrease appears to be less when ethanol was administered simultaneously. Renal (Na+ + K+ATPase activity was suppressed after lead administration, but it was stimulated after ethanol administration. the suppression of renal (Na+ + K+ATPase activity after lead administration was diminished after simultaneous administration of ethanol and lead. the diminution of the suppression appeared to be associated with a corresponding reduction in urinary Na+ excretion. more...

Urinary excretion of water and sodium were markedly elevated by lead administration (a single oral dose of 200 mg Pb/kg), while urinary potassium excretion was elevated to a lesser extent. A decrease in serum sodium caused by natriuresis was observed in lead-treated rats. The renal (Na + + K + )ATPase activity was markedly decreased 6 hr after lead administration. more...

A method for predicting the effective sound level (ESL) is proposed in this paper. The effective sound level is the sound level of a steady noise which produces the same subjective magnitude as a fluctuating noise and may be measured as the point of subjective equality by means of psychometric methods. The proposed method gives the predicted value of ESL which is denoted as Leff, based on an assumption of integration and averaging of subjective magnitude. It has been shown that Leff can be expressed by an equation which contains the probability density function of the level distribution and two empirical parameters, the values of exponents for sound pressure and duration in the psychophysical function. The practical significance of the descriptor Leff was discussed in terms of the definition of the number of events. High correlation between Leff and the subjects’ response was found. more...

Thyrocalcitonin (TCT; 80 MRC mU/l00g) administered SC to intact and thyroparathyroidectomized rats, caused a significant decrease in serum calcium, while increasing the liver calcium concentration. The accumulation of calcium in the liver, induced by TCT, was potentiated by the injection of calcium in both intact and thyroparathyroidectomized rats. In thyroparathyroidectomized rats, the administration of imidazole (30 mg/100 g) produced a significant increase in liver calcium and a corresponding fall in serum calcium. The rise in liver calcium produced by TCT was slightly potentiated by prior administration of imidazole, but was not enhanced by prior administration of theophylline (12 mg/100 g) which caused a significant elevation of serum calcium. These results suggest that the action of TCT on liver calcium does not involve cyclic AMP. (Endocrinology 96: 1004, 1975) more...

社内情報化におけるパーソナルコンピュータ(パソコン)とワークステーションに関して述べた。定義を検討し, それぞれの歴史と現状について述べるとともに, その中で社内情報化にとって重要な技術の展開を概観した。次に社内情報化のためのチェックポイントとして, 日本語入力機能, マルチメディア機能, ネットワーク機能について検討した。日本語入力機能については, これに含まれる要素技術を解説し, 日本語文書作成の道具の選択を論じた。比較的新しい機能であるマルチメディア機能とネットワーク機能については, 現状の紹介と応用を示した。 more...

The activity of β-glucuronidase and β-galactosidase in the femur of rats was examined after single intraperitoneal administration of lead (10.0 mg/100 g) or cadmium (0.15 mg/100 g) acetate, and the following results were obtained. Bone β-glucuronidase and β-galactosidase activities increased significantly (p more...

In this paper, the exponentially distributed vehicles model in which attenuation effect of noise is taken into consideration was treated in the first place. The mean and the variance of sound intensity and approximate expression for mean of sound pressure level (SPL) were derived. Secondly, the mean and the variance of sound intensity based on an Erlang distribution model were derived. Approximate value of mean of SPL at an observation point on the road was also obtained. more...

The effects of porcine calcitonin (CT), salmon CT, or synthetic eel CT ( [Asu1, 7] ECT) on the calcium concentrations in the bile and serum have been examined after a single intraperitoneal administration of calcium chloride to thyroparathyroidectomized rats. The administration of these hormones (80 MRC mU/100 g body weight, respectively) markedly increased calcium excretion into the bile within 1 hr after the injection of calcium chloride (4.0 mg Ca/100 g). The effect of synthetic eel CT was more prolonged than that of any other hormone (up to 3 hr after administration). The administration of porcine CT, salmon CT, or synthetic eel CT significantly inhibited the elevation of serum calcium concentration within 1 hr after the injection of calcium. The serum calcium concentration was slightly decreased at 3 hr after the administration of salmon CT or synthetic eel CT. These results suggest that the lowering effect of CT on the serum calcium level results partly from the stimulation of calcium excretion into the bile. more...

The effect of tin on bile calcium content has been investigated in rats given stannous chloride orally. The bile calcium content was linearly increased by a single oral administration of tin (10, 30, or 50 mg of Sn/kg). The administration of tin also caused a significant increase in the bile calcium content of both fasted rats and thyroparathyroidectomized rats. Meanwhile, the administration of tin did not elevate the calcium concentration in the liver. These results indicate that the augmentation of the bile calcium content after tin administration does not result from calcium accumulation in the liver. Moreover, the bile calcium content was markedly increased by the oral administration of tin (30 mg/kg every 12 hr) for 3 days, while the serum calcium concentration was reduced significantly. The present results suggest that the hypocalcemic effect of tin is partly caused by an increase in the calcium content of the bile. more...

A technique for the blood volume measurement of newborns was established in which nonradioactive 50Cr was used in patients for whom radioactive labels were not advisable. The red blood cells (RBC) in the newborn's blood withdrawn from umbilical cord after birth were tagged with enriched stable isotope 50Cr (96%, normal abundance 4.3%) and reinjected into the newborn. Blood samples (0.5 ml) were withdrawn at 30 min and thereafter at 6, 12, 24, 48, 72 and 120 hours old. Samples were centrifugalized and portion of RBC was then freeze-dried, weighed and sealed into polyethylene sheet bag together with 50Cr standard. Neutron irradiation was performed in the reactors of the JAERI with thermal neutron flux 5 X 10(13), 2 X 10(13), 8 X 10(13) cm-2s-1 at JRR-2, -3 and -4 respectively for 20 min and samples were left for about two weeks after irradiation. Induced radioactivity (51Cr, 59Fe) of the sample was measured with a Ge(Li) gamma-ray detector system and 4096 channels pulse height analyzer. Analysis of activity data was carried out by BOB-76 code. The RBC and total blood volume of the newborn was calculated using an isotopic dilution technique. We have investigated on tagging efficiency of 50Cr to RBC, washing effect and dilution rate by 50Cr content or 51Cr/59Fe ratio. Significant difference was observed in the total blood volume of newborns depending on the delivery style and in addition, it changed dynamically along the time elapsed after birth. more...

There are some approaches to an understanding of the relationships among many qualitative variables.Depending, among them, specifically upon L.A. Goodman, this paper aims at analysing the interactions in dichotomous and polytomous variables on the basis of different to kinds of the following data : (1) Four-way table concerning teachers' attitudes in Wakayama.(2) Three-way table concerning the subscription to a newspaper.As the result of the above analyses, this paper can offer the following advantages of the Goodman-model : his model is the multiplicative form and usually fitter for data than the additive form ; in addition, compared with the usual models, the Goodman-model makes it easier to calculate not only the main-effects but all the interaction-effects among the variables. This can be said even if variables increase in number.Goodman, however, assumes that the magnitude of the effects of one variable upon the other is equal to the one in a reversed case. But if the magnitude in two directions are considered to be different, then the Goodman-model will have to modified, and we shall need to develop a new model. more...

The Japan Association of Industrial Health (J.A.I.H.) recommends the permissible criteria for noise exposure for hearing conservation as is shown in Fig. 1 and Table 1. In the criteria, permissible octave band levels or permissible one third octave band levels are given as a function of exposure time. J.A.I.H. also recommends a provisional permissible sound level of 90 dBA for 480 minute exposure. The criteria is based on the critical band theory of temporary threshold shift (TTS) and the empirical equations for predicting TTS; in the sense that the criteria has been rationally determined.According to the survey conducted by A rchitectural Institute of Japan, however, permissible criteria are determined in terms of the sound level in most of the countries (Table 2). This is considered to be due to the fact that simpler methods are needed than those which request frequency analyses. In an effort to meet this need, a simplification of the permissible criteria for noise exposure recommended by J.A.I.H. has been undertaken. A comprehensive noise survey of the plants provided in Labor Safety and Sanitation Ordinance furnished 265 measurements that were used to relate A-weighted sound levels to the octave band contours of Fig. 1. Octave band levels are averaged on center frequency and the mean values are shown in Fig. 2. In the figure, the ranges of standard deviations are also shown. The noises are sorted into groups by their octave band levels (Table 3). Examples of noise spectra sorted into the groups are shown in Fig. 3. The permissible sound levels of the sound which has a typical industrial noise spectrum as is expressed by the curve a of Fig. 2 are given by the A-weighted sound levels when the curve a of Fig. 2 osculates the curves of Fig. 1. The permissible sound levels so obtained are shown in the row a of Talbe 4. The permissible sound level obtained in the same ay for the curve b of Fig. 2 is also shown in the row b of Table 4. The distribution of permissible sound levels obtained as above stated for each of 265 industrial noises are shown in Fig. 4. The means of the distribution and the values of means minus one standard deviation are presented in the rows c and d of Table 4 respectively. If thepermissible sound levels are determined as the values in the row a or c of Table 4, about a half of the noises are placed, on the basis of their A-weighted sound levels, into a group where noise hazard is underestimated. If they are determined as the values in the row b or d of the talbe, about 17 percent noises are grouped unsafe. In order to determine he permissible sound levels with a reasonable proportion of noises grouped unsafe, the permissible sound levels for proportions from 10 to 90 percent of the noises grouped unsafe are calculated and presented in Table 5. The levels for 10, 50, and 90 percent are plotted against exposure time in Fig. 5, which shows the trading relations between the sound level and the exposure time, the proportion being constant. Though the curves expressing the trading relation are hyperbolic, it would be more appropriate to apply a linear trading relation for simplification. In Fig. 5, EPA's criteria and OSHA's standard are shown for comparison. EPA adopts 85 dBA for 8 hour exposure with 3 dB rule and OSHA does 90 dBA with 5 dB rule. From the figure one can see that the trading relation is approximated better by 3 dB rule than by 5 dB rule except the shorter exposure time than 60 minutes. The permissible level of 90 dBA for 8 hour exposure seems to be unsafe, because the percentage of the noises grouped unsafe exceeds 50 percent. Hence the present authors propose the permissible sound level of 85 dBA for 8 hour exposure with the trading relation of 3 dB rule. The proportions of the noises grouped unsafe and those grouped overprotected, when the permissible sound level is applied, are shown in Table 6. A noise is grouped overprotected when the sound level is equal to the permissible sound level of a more...

The threshold of acoustic reflex (AR) was measured in workers exposed to occupational noise. White noise (WN), and pure tones of 1 and 4 kHz were selected as activating stimuli for AR. The results were compared with the thresholds of AR (ART) in the normal group (Group C) reported by the authors previously. To examine in relation between noise exposure and ART, the exposed group was classified into two groups by their hearing levels (HL) at 4 and 8 kHz; i.e. Group D (HL(4k + 8k)/2 less than 25 dB) and Group E (HL(4k + 8k)/2 greater than or equal to 25 dB). A significant (P less than 0.001) elevation of ARTWN was observed not only in Group E (8.8 dB) but also in D (7.5 dB) with normal hearing acuity. A significant (P less than 0.001) lowering of ART1k was observed in Group E only. The difference between ART1k and ARTWN, [ART1k-ARTWN], was reduced significantly (P less than 0.001) in the exposed groups; i.e. 12.4 dB in Group C, 3.7 dB in Group D and 0.6 dB in Group E. These results suggested that the value of [ART1k-ARTWN] may be used as a sensitive and objective indicator for detecting and evaluating the early stages of noise-induced hearing impairment and individual susceptibility to noise. more...

The effect of tin on intestinal calcium absorption was studied in rats given stannous chloride (Sn, 30 mg/kg every 12 hr) orally for 3 days. The increase of serum calcium concentration after a single oral administration of calcium chloride (Ca, 500 mg/kg) was significantly inhibited by the prior administration of tin. Calcium concentrations in duodenal mucosa were also reduced to one-third of control values by the administration of tin. The calcium-binding activity in the supernatant fraction of 38,000 g of the mucosal homogenate was decreased to one-quarter of control values, and alkaline phosphatase activity in the mucosal homogenate was markedly lowered by the administration of tin. These results suggest that the oral administration of tin inhibited the duodenal active transport of calcium. more...