We are now at the stage of neurophysiology where learning and memory can be subjects of studies at a strictly molecular level, on the basis of the well-established finding that these higher nervous activities are sustained by, and formed in, the physicochemical events of specified neural mechanisms in the brain. As for the neurophysiological process of memory, much evidence has shown that short-term memory and long-term memory probably result from different molecular events in the brain, i.e., the former from reversible chemical modification of the synapses concerned, and the latter from reorganization of the synapses following synthesis of protein and its axonal. transport, which causes the enduring consolidation of memories.
How does the experience of individual organisms trigger the protein synthesis in the brain required for long-term memory? What is the role of protein molecules thus formed? What is the mechanism for the regulation of gene expression in the reorganization of neuronal circuits? Many such difficult problems need to be solved. Recently, cholinergic and glutamatergic neuron networks have attracted much attention because there is a strong possibility that they play a critical role in memory. The clinical implication of these findings in human memory deficit, as exemplified in senile dementia, further emphasizes the importance of neurobiological elucidation of the molecular mechanism for learning and memory.

View full abstract

This study was undertaken to compare and re-examine the relation of lactate threshold (LT) and ventilatory threshold (VT), using six objective determination methods proposed previously. Twenty-one young male subjects performed a cycle exercise test in which the work rate was increased by 150kg•m every 2min up to his limit of volitional fatigue. Through each test, gas exchange parameter measurements were made every 1min (every 30s at nearly maximal level), and the venous blood samples were taken from a warmed ear lobe at each work rate for determining blood lactate concentration. LT and its variance were determined by the intersecting straight lines regression. LT ranged from 0.72 to 1.40l/min in terms of V_O2, and the mean value of S.D. for each LT was about 0.1l/min. Each objective method for determining VT used in this study was based on the simple modelling of the criterion for visual detection of VT, that is the non-linear increase in VE or the systematic increase in VE/V_O2. When the relationship between LT and VT was examined, VT by the objective methods based on determining minimum value of VE/V_O2 showed relatively high consistency with LT. Of 16-20 individuals out of all 21 subjects, there were VT within LT±0.2 in V_O2. It is concluded that VE/V_O2 is a more sensitive index for detecting VT than VE in the gas exchange parameters, and the objective VT determination method based on minimum value of VE/V_O2 could facilitate estimation of LT within an error of±0.2l/min V_O2 in most normal individuals.

View full abstract

The hemodynamic characteristics of Nuclepore (NP) membrane filtration were evaluated from a pressure (P)-flow rate (Q) relationship of erythrocyte suspension obtained by the vertical-tube method (NICHOL et al., 1951) with a slight modification. It became evident that the vertical-tube method was a more quantitative and simple method than the conventional steady flow perfusion method using a variable speed pump. The P-Q relationship of erythrocyte suspensions in the perfusion of NP membrane consisted of a smooth curve convex to the P-axis at low P tending to a straight line at high P. The extrapolated linear segments of P- Q curves of erythrocyte suspension did not converge to the same point on the negative Q-axis, that is, the value of the negative intercept increased as flow decreased. This observation indicated clearly an obstruction or plugging of the pores by erythrocytes. It was made clear that flow rate measured with NP membrane filtration was influenced not only by intrinsic red cell deformability but also by several different factors, namely, the different distribution of pore size of NP membrane, microdust contaminated inevitably in red cell suspension, total volume of cell suspension through NP membrane, stagnation or retention of erythrocyte suspension and the hematocrit value of suspension. In conclusion, the present study shows that the precise definition of deformability depends on the method or rheological conditions, such as hematocrit value of suspension, used to measure it, even if confined within NP membrane filtration.

View full abstract

Effect of Creatine depletion by β-guanidinopropionic acid (β-GPA) feeding on mitochondrial morphology was studied in rats. Following β-GPA feeding for 9 weeks, intramitochondrial inclusions running parallel to the long axis of mitochondrion were observed in skeletal muscles. A bundle of inclusions consisted of four parallel arrays containing electron-dense materials. Two outer arrays were continuous with cristal membranes and two inner arrays were chains of fine particles. Mitochondria with such inclusions were elongated probably in only a certain direction even though it was suggested that the layers of cristae were straightened two-dimensionally. Longer mitochondria ran parallel to the muscle fibers. It was also suggested that chronic stimulation of mitochondria biogenesis by depletion of high energy phosphates may induce such inclusions within mitochondria.

View full abstract

We examined the relationship between body temperature, tail vasomotor response, and work intensity at different ambient temperatures in rats, using a treadmill and continuously measuring oxygen uptake during exercise. At an ambient temperature (T_a) of 24°C, rectal temperature (T_re) at the beginning of tail vasodilation during exercise increased in proportion to work intensity. After tail vasodilation T_re remained steady, and at the end of 30min exercise T_re level was proportional to work intensity. At T_a of 14°C, T_re at the end of exercise was slightly higher than at 24°C, and was higher at higher work intensities. At T_a of 4°C, T_re rose slower during exercise than at higher T_as and even dropped at relatively low work intensities. Tail vasodilation did not occur in most cases. At T_a of 34°C, T_re rose continuously during exercise. These data indicate that body temperature of rats during exercise rises in proportion to work intensity, but the extent of body temperature rises differs according to T_a.

View full abstract

The thermopreferendum (preferred temperature) of the Japanese freshwater snail (Semisulcospira libertina) was determined in an aquatic temperature gradient after injection of prostaglandin E₁, Prostaglandin E₂, and LPS. Injected doses of each pyrogen ranged from a toxic dose to less than 1/20th of the toxic dose. Toxic effect of the highest doses of pyrogen disappeared within 120min. No fever occurred during the 150min observation following the pyrogen injection. The present results support the hypothesis that fever was selected as a way of defending against infection only after the period of the emergence of the mollùscus, i.e., the early Cambrian period.

View full abstract

In order to clarify whether the sodium handling of smooth muscle is associated with the relaxing action of α-human atrial natriuretic polypeptide (α-hANP), we examined the sodium pump-related effects of α- hANP on rat aortic smooth muscles. Application of Ca²⁺ (1.0 to 10.0mM) to the muscle preincubated in Ca²⁺-free, and K⁺-free or 0.5mM K⁺ medium for 60min induced a contraction. Pretreatment with α-hANP (1×10^-8M) decreased the contraction evoked in 0.5mM [K⁺]_o but not that in K⁺-free medium. After a contraction was elicited by norepinephrine in K⁺-free solution, an addition of KCl (1.4-5.4mM) caused a transient relaxation in a concentration-dependent manner, presumably due to the activation of electrogenic Na pump. The α-hANP enhanced the relaxation, which was sensitive to ouabain, and the potentiation by α- hANP was inversely related to the concentration of K⁺ added. When α- hANP was applied to relax the muscle precontracted by norepinephrine in the varied concentration of external K⁺, α-hANP-induced relaxation was greater in 1.4 or 2.7mM [K⁺]_o than in 0 or 5.4mM [K⁺]_o. These results suggest that the vasodilating effect of α-hANP is at least partially mediated by the activation of electrogenic Na, K-pump and this effect is prominent when the Na, K-pump is partially suppressed.

View full abstract

The effects of noradrenaline (NA) injection (40μg/100g, i.p.) on plasma glucagon, corticosterone (CS), deoxycorticosterone (DOCS), glucose, and free fatty acids (FFA) were investigated in cold-acclimated rats (CA) and warm controls (WC). The CA were transferred to warm control temperature ca. 18h prior to NA or saline injection. The animals were decapitated and the trunk blood was collected 0, 10, 20, and 40min after the injection. Plasma glucagon level increased significantly during the experimental period after NA, while saline did not influence its level. The magnitude of increase as assessed by 95% confidence interval was significantly greater in CA than in WC. Plasma CS and DOCS were significantly increased by saline injection, but NA caused greater elevations of these steroid-hormones. The magnitudes of increases were also greater in CA. In contrast to the hormonal responses, NA-induced increases of plasma glucose and FFA levels were smaller in CA than in WC. These results suggest that glucagon and glucocorticoids are released, at least partly, by NA, and these thermogenic factors act in synergism, enhancing nonshivering thermogenesis through an accelerated utilization of energy substrates such as glucose and FFA.

View full abstract

Blood (5 to 15ml) was infused into aorta of the anesthetized rabbit through the carotid artery or femoral artery at a constant rate (0.55 to 8.3ml/s). The carotid sinuses were occluded. The systemic arterial pressure (SAP) began to rise immediately at the onset of the infusion and dropped gradually in most cases during the infusion. SAP continued to decline after the infusion and in many cases became lower than the pre-infusion pressure. Within seconds, SAP tapered off to its lowest point and resumed a gradual rise, leveling off higher than its initial pressure. A depressor effect caused by the rapid infusion of blood into the aorta (DRIA) was observed in every rabbit. DRIA was not suppressed much by the section of aortic or vagal nerves. DRIA was markedly suppressed by the administration of α-adrenergic blockade, but β-adrenergic blockade had little effect on DRIA. By using a hydraulic model of the closed circulatory system, a theoretical analysis was made on the basis of the "theory of active fluid element, " a theory developed by Hatakeyama, one of the authors, and it was demonstrated that DRIA must not be considered to be a passive hemodynamic phenomenon. The results obtained suggest that a nervous regulatory mechanism -rather than the reflex via the carotid sinus or aortic baroreceptors, or other mechanoreceptors-plays an important part in the venous and the cardiac regions.

View full abstract

The combination of NaF and AlCl₃ stimulated histamine secretion from digitonin-permeabilized rat mast cells only in the presence of trace amount of Ca²⁺. When NaF plus AlCl₃ were added together with a maximal dose of guanosine-5′-[γ-thio]triphosphate (GTPγS), the combined effect was less than additive. The results suggest that the secretory effect of fluoroaluminates is, at least partially, mediated by GTP-binding protein, which is previously found to be activated by GTPγS.

View full abstract