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Biomedical subjects

T Asami

Publications and source records attributed to T Asami.

At least 109 records · Page 6Linked to original sources

Responses of anterior hypothalamic-preoptic thermosensitive neurons to thyrotropin releasing hormone and cyclo(His-Pro).

Effects of local application of thyrotropin releasing hormone (TRH) and its metabolite, histidyl-proline diketopiperazine [cyclo (His-Pro)], on the activity of thermosensitive and thermally-insensitive neurons of the anterior hypothalamic-preoptic area were investigated in urethane-anesthetized rats. Microelectrophoretic application of TRH changed the activity of 126 of 206 neurons tested. Thyrotropin releasing hormone predominantly decreased the activity of warm-sensitive neurons and increased the activity of cold-sensitive neurons. Since it has been generally assumed that warm-sensitive and cold-sensitive neurons in the anterior hypothalamic-preoptic area mediate heat and cold defence responses, respectively, the present results are consistent with previous findings showing hyperthermia after injection of TRH into the hypothalamus in the rat. Cyclo (His-Pro) affected the activity of 59 of 153 neurons tested. In addition, cyclo (His-Pro) did not preferentially affect warm- or cold-sensitive neurons. These results indicate that the previously-determined hypothermic effect of cyclo (His-Pro) cannot be explained by its effects on thermosensitive neurons in the anterior hypothalamic-preoptic area.

Animals↗

Responses of anterior hypothalamic-preoptic thermosensitive neurons to substance P and capsaicin.

The effects of capsaicin and substance P, applied locally, on the activity of thermosensitive and thermally-insensitive neurons in the anterior hypothalamic-preoptic area were studied with the use of multibarrelled microelectrodes in the urethane-anesthetized rat. In a total of 34 thermosensitive neurons (21 warm-units and 13 cold-units) in the anterior hypothalamic-preoptic area, only 7 units responded to substance P and 27 units (79.4%) were not affected. In contrast, 23 of 57 (40.4%) thermally-insensitive neurons responded to substance P. Of 74 thermosensitive and thermally-insensitive neurons tested with both substance P and capsaicin, only 7 units (9.5%) showed the same direction of change in activity in response to the application of both drugs. The majority of the neurons responded to only one of the drugs (32 units, 43.2%) or responded to substance P and capsaicin in opposite directions (9 units, 12.2%). A substance P antagonist, (D-Pro2, D-Trp7,9)-substance P, blocked the substance P-induced excitatory responses in 5 of 6 neurons tested in the anterior hypothalamic-preoptic area, but not the capsaicin-induced excitatory or inhibitory responses (n = 5). It is unlikely that substance P in the anterior hypothalamic-preoptic area participates in the hypothermic effects of capsaicin, observed after local injection.

Anesthesia↗

Effects of naloxone and picrotoxin on diazepam- or pentobarbital-induced hyperphagia in nondeprived rats.

Diazepam and pentobarbital administered intravenously increased food intake in a dose-dependent manner in nondeprived rats. Low doses of naloxone inhibited diazepam-induced feeding, but did not inhibit pentobarbital-induced feeding. On the other hand, picrotoxin inhibited feeding induced by both drugs. These findings suggest that diazepam-induced hyperphagia is related to endogenous opioid mechanisms, but pentobarbital-induced hyperphagia is not. Hyperphagia induced by both drugs may be related to GABAergic neurons.

Animals↗

Effects of interleukin-1 and arachidonate on the preoptic and anterior hypothalamic neurons.

Effects of microelectrophoretic application of ultrapure human interleukin-1 (IL-1), an endogenous pyrogen, on the activity of 80 neurons in the preoptic and anterior hypothalamus (PO/AH) were investigated in the urethane anesthetized rat. IL-1 predominantly decreased the activity of warm-sensitive neurons (15 of 19) and increased the activity of cold-sensitive neurons (10 of 12), but had no effect on 37 of 49 thermally insensitive neurons. The neuronal responses to IL-1 were blocked or attenuated by concurrent application of mepacrine (a phospholipase inhibitor) or sodium salicylate (a cyclooxygenase inhibitor). Local application of sodium arachidonate decreased the activity in 17 of 28 warm-units and excited 12 of 16 cold-units, and the effects of arachidonate were blocked by sodium salicylate. The results are compatible with the view that one or more cyclooxygenase metabolites of arachidonic acid are involved in the IL-1 induced fever.

Animals↗

Thermally-induced activities of the mesencephalic reticulospinal and rubrospinal neurons in the rat.

Unit activities of 226 midbrain reticulospinal (mRfS) and non-mRfS neurons and 238 rubrospinal (RbS) and non-RbS neurons were investigated during changes in temperatures of midbrain (Tmb), preoptic and anterior hypothalamus (Thyp) and skin (Ts) in the urethane-anesthetized rat. Responsiveness to Tmb, Thyp and Ts were found in 43.5%, 41.6% and 51.5% of neurons of midbrain reticular formation (mRf), and in 35.2%, 32.7% and 17.6% of neurons of red nucleus (Rb). Higher incidence of responsiveness to remote temperatures was found among Tmb responsive neurons than Tmb unresponsive neurons in both mRf and Rb. The mRf contains significantly greater numbers of neurons having such multiple thermal responsiveness and also of neurons which were activated by falls in temperatures (cold-responsive neurons) than the Rb. These characteristics were more conspicuously seen among mRfS neurons, showing a high degree of convergence of cold signals from different sites of body. On the other hand, RbS neurons did not differ from non-RbS neurons regarding thermal characteristics and showed no particular combinations of responsiveness to temperatures of different sites. Microinjection of procaine and glutamate into the mRf just dorsolateral to the Rb, but not into the Rb, decreased and increased cold-induced increase in EMG activity and shivering without changes in cardiovascular and respiratory parameters and pilomotor activity. The results suggest that mRfS neurons are involved in the control of thermoregulatory muscle tone and shivering.

Action Potentials↗

Convergence of thermal signals on the reticulospinal neurons in the midbrain, pons and medulla oblongata.

A total of 670 reticulospinal (RfS) and non-RfS neurons in the mesencephalic, pontile and medullary reticular formation (mRf, pRf and mdRf) were studied for the responsiveness to changes in temperatures of local brain sites, preoptic and anterior hypothalamus (PO/AH) and skin in the urethane anesthetized rat. Local thermoresponsiveness was found in 49.6% of 139 mRf neurons, 61.9% of 160 pRf neurons and 75.4% of 126 mdRf neurons. While the ventromedial region of pRf and mdRf contained predominantly warm-responsive neurons (54.8% and 62.5%), cold-responsive neurons were much more frequently found in the mRf (33.8%) and the dorsolateral region of pRf (41.9%) and mdRf (50.0%). Responsiveness to hypothalamic temperature and/or skin temperature was observed in about 40-74% of Rf neurons. Higher incidence of responsiveness to remote temperatures was found among locally thermoresponsive neurons than among locally thermounresponsive neurons in all three areas. Particularly, there was a high degree of convergence of 'cold' signals from local and remote sites on the RfS neurons in the mRf and the dorsolateral pRf and mdRf. Microinjections of procaine and glutamate into these regions decreased and increased the cold-induced increase in EMG activity and shivering without any correlated changes in cardiovascular and respiratory parameters and pilomotor activity. The results suggest that RfS and non-RfS neurons in the mRf and the dorsolateral pRf and mdRf are involved in the control of thermoregulatory muscle tone and shivering.

Action Potentials↗

Intravenous self-administration of diazepam in rats.

Diazepam 0.5-2.0 mg/kg per injection was self-administered intravenously by rats on a continuous reinforcement schedule in a dose-dependent manner over a 30 day period. The rates of diazepam self-administration were relatively stable after responding was established, in comparison with rats self-administering morphine 0.5 mg/kg per injection whose rates continued to increase. At a fixed ratio 4 or 8 schedule, higher maximum rates of responding were seen with diazepam than with morphine. During withdrawal, reductions in body weight tended to occur in a manner dependent on the preceding rates of diazepam self-administration and were possibly caused by physical dependence. These findings suggest that diazepam acts as an intravenous reinforcer in rats and that the procedure we describe is of use to predict the dependence liability of drugs considered to have only a weak potential for abuse.

Animals↗

Elevation of cerebrospinal fluid sialic acid concentration in children with central nervous system leukemia.

We studied sialic acid in the cerebrospinal fluid (CSF) of 52 children with leukemia and 51 children with non-leukemic diseases. The CSF sialic acid concentration in the children with central nervous system (CNS) leukemia was significantly higher than that in the children with acute lymphoblastic leukemia without CNS involvement, acute non-lymphocytic leukemia without CNS involvement, non-hemopoietic diseases, non-suppurative meningitis, epilepsy, and other neurologic diseases. Serial determinations revealed a rapid decline in the CSF sialic acid concentrations in the patients with CNS leukemia who responded well to the therapy and who were free from relapse of CNS leukemia. The simultaneously determined CSF beta 2 microglobulin concentration did not show any significant changes. These results suggest that the CSF sialic acid may be a good indicator of CNS leukemia.

Adolescent↗

The inhibition of neoplastic cell proliferation with human natural tumor necrosis factor.

Purified human natural tumor necrosis factor (n-TNF) was prepared by stimulating human leukemic B cell line (BALL-1) with Sendai virus. The colony formations of all of 18 human cancer-derived abnormal cell lines were suppressed by 10(1)-10(6) U/ml of n-TNF, while n-TNF was nontoxic to all human normal fibroblast cells. This in vitro inhibition of cell growth was reversible. In breast adenocarcinoma MCF7 cells treated with n-TNF a specific decrease of DNA synthesis was observed, and DNA histograms showed a block at G1 in the cell cycle. In vivo studies revealed that n-TNF suppressed the tumor growth of murine Meth A sarcoma, human renal adenocarcinoma (ACHN), malignant melanoma (SK-MEL-28) and glioblastoma (U-373 MG). Isobologram analysis showed that n-TNF synergistically inhibited cell growth in combination with human natural interferon (IFN)-a. In vivo synergism of n-TNF and IFN-a was also found in the U-373 MG tumor model implanted into nude mice.

Animals↗

Mechanical efficiency in rowing.

Five university oarsmen participated in a determination of mechanical efficiency when rowing in a tank. In the tank, water was circulated at 3 m X s-1 by a motor driven pump. The subjects rowed with the stepwise incremental loading, in which the intensity increased by 10% of the maximum force of rowing (maxFc) every 2 min. Power (WO) was calculated from the force applied to the oarlock pin (FC) and its angular displacement (theta H). Oxygen uptake and heart rate were measured every 30 s during rowing. Anaerobic threshold (AT) was determined from expired gas variables by Wasserman's method. AT of oarsmen was 74.6 +/- 6.01% as a percentage of VO2max. As the displacement of the handgrip in the stroke was independent of WO, the increment of WO was caused by the increase of both FC and stroke frequency. Gross efficiency without base-line correction (GE) increased with FC with low intensities of rowing. In the region of 124-182 W of WO GE was almost constant at 17.5%. Efficiency was 19.8 +/- 1.4%, with resting metabolism as base-line correction (net efficiency), and 27.5 +/- 2.9% when using the unloaded rowing as the base-line correction (work efficiency), and 22.8 +/- 2.2% when calculating the work rate as the base-line correction (delta efficiency).

Adult↗

[Basic study on human interferon-beta: Part III. The mechanisms of its antitumor effect].

The mechanisms of the direct and indirect antitumor effects of human interferon-beta (IFN-beta, MR-21) were examined. IFN-beta suppressed DNA, RNA and protein synthesis in cells derived from human tumor. The expression of cellular oncogenes (c-Ha-ras and c-myc) in tumor-originated cells was also suppressed by IFN-beta. These results suggest that such suppression is one possible mechanism of the direct anticellular effect induced by IFN-beta. IFN-beta augmented NK cell activity and the ADCC activity of human peripheral blood lymphocytes. It is also suggested that these are two of the immune system-mediated mechanisms responsible for the indirect antitumor effect of IFN-beta in vivo.

Antibody-Dependent Cell Cytotoxicity↗

[The effect of vigorous exercise training on cholesterol metabolism in rats].

Twenty-eight male Wistar rats, aged 7 weeks, were subjected to a vigorous exercise regimen of running for 5 weeks and 35 rats were selected as their controls. After 5 weeks both exercised and control rats were injected 2 microCi of 14C-mevalonate per 100 g body weight into peritoneal cavities and sequentially sacrificed at 20, 40, 60, 80, 100, 120, and 180 min after the injections in each subgroup. The exercised rats showed a significantly lower level of serum total cholesterol than the control rats. The activity of HMG-CoA reductase in liver microsome was significantly higher in the exercised rats than in the control rats. No differences existed in intestinal HMG-CoA reductase activity between exercise and control groups. The incorporation of mevalonate into liver cholesterol and serum cholesterol (especially HDL fraction) in the exercised rats were significantly higher compared with these of the control. Furthermore, the exercised rats showed a higher rate of cholesterol synthesis activity in liver. From these results it was concluded that the hepatic lipoprotein cholesterol production was elevated by exercise compared with that of control.

Animals↗

[Basic study on interferon-beta: Part IV. Antitumor effect on nude mouse-transplanted human tumors].

The effects of human interferon-beta (IFN-beta, MR-21) on the growth of xenografted human tumors in nude mice were examined. IFN-beta was administered to mice with malignant melanoma (SK-MEL-28 and Sk-14) intratumorally at a dose of 1 X 10(5)-3 X 10(5) IU/mouse, with acute leukemia (CCRF-HSB-2) intratumorally at a dose of 3 X 10(5) IU/mouse, with glioblastoma (U-373 MG) intravenously or intratumorally at a dose of 1 X 10(5)-6 X 10(5) IU/mouse, or with uterine cervical tumor (HeLa S3) intravenously at a dose of 0.3 X 10(5)-1 X 10(5) IU/mouse. IFN-beta inhibited the growth of all of these tumors in a dose-dependent manner.

Acute Disease↗