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Biomedical subjects

I Nakagawa

Publications and source records attributed to I Nakagawa.

At least 19 recordsLinked to original sources

[Asphyxial death by laryngopharyngeal tumor--two autopsy cases].

Case 1. A 44-year-old male died about 3 h after paracenteses of both palatine tonsils. A 6.5 x 2.5 x 2.0 cm tumor, caused by bleeding and edema, was revealed at medico-legal autopsy. This tumor extended from the right palatine tonsil to the right edge of epiglottis. The cause of death was determined to be acute asphyxia due to the obstruction of the airway by the tumor. Case 2. A 51-year-old female was thought to have been killed by manual strangulation. At medico-legal autopsy, three malignant tumors, each of which was not as large as the tip of the little finger, were found in the lower pharynx. There were no findings of acute asphyxia death. The cause of death was determined to be delayed asphyxia caused by the malignant tumors.

Adult

Interaction between opiate subtype and alpha-2 adrenergic agonists in suppression of noxiously evoked activity of WDR neurons in the spinal dorsal horn.

Several studies have demonstrated synergistic antinociception following low-dose administration of morphine and alpha-2 adrenergic agonists at the spinal level. This study was carried out in order to identify the opiate subtypes that are likely to be involved in such synergistic suppression of noxiously evoked activity of wide-dynamic-range (WDR) neurons in the dorsal horn of the spinal cord. We also examined the effect of opiate antagonists and alpha-2 adrenergic antagonists on the suppression produced by opiate or alpha-2 adrenergic agonists. Extracellular activity of single WDR neurons in the spinal dorsal horn, which was evoked by a radiant heat stimulus (51 degrees C), was recorded in decerebrate, spinally transected cats. Agonists were administered spinally and antagonists intravenously. In the synergism study, ineffective doses of the moderately selective mu agonist morphine (25 micrograms), the delta agonist DADL (20 micrograms), and the selective delta agonist DPDPE (30 micrograms), when combined with an ineffective dose of the alpha-2 adrenergic agonist clonidine (5 micrograms) produced significant synergistic suppression of noxiously evoked WDR neuronal activity. However, the ineffective or slightly effective dose of the selective mu agonist DAGO (1 or 1.5 micrograms, respectively) did not show any synergistic action with clonidine. Furthermore, the synergism between morphine and clonidine was reversed by the selective delta antagonist ICI 174,864. We interpret these results to indicate that opiates interact at spinal delta receptors to produce a synergistic suppression of evoked WDR neuronal activity in the presence of spinal clonidine. An alternative explanation is that ICI 174,864 may interact in some way with alpha-adrenergic systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists

Serotonergic mediation of spinal analgesia and its interaction with noradrenergic systems.

Serotonin was administered intrathecally onto cat spinal cords to evaluate the pharmacology by which it suppresses noxiously evoked activity of wide-dynamic-range (WDR) neurons in the spinal dorsal horn. Doses of 500, 1,000 and 2,000 micrograms serotonin produced significant suppression of the mean noxiously evoked activity of WDR neurons in the dorsal horn of the spinal cord (21, 44, and 69% at 30 min, respectively). The dose-dependent effects were partially reversed by the intravenous administration of the serotonin antagonist methysergide (1 or 2 mg). Intravenous administration of the alpha 2-adrenergic antagonist yohimbine (0.5 or 1.0 mg/kg) produced a significant antagonism of the effects of serotonin. In contrast to the effects of methysergide and yohimbine, intravenous administration of naloxone or the alpha 1-antagonist corynanthine had no effect upon the suppressive effects of serotonin. The combination of low-dose serotonin and low-dose clonidine produced a supraadditive effect (30% at 30 min). These data support the concept that noradrenergic systems, possibly through an alpha 2-adrenergic mechanism, are involved in the modulation of spinal WDR neurons by serotonin.

Anesthesia, Spinal

The antinociceptive role of mu- and delta-opiate receptors and their interactions in the spinal dorsal horn of cats.

This study was undertaken to examine the antinociceptive roles of different subtypes of opiate receptors and their interactions at the level of the spinal cord. We recorded extracellularly the activity of the single wide dynamic range neurons evoked by noxious radiant heat (51 degrees C) in decerebrate, spinally transected cats. The separate intrathecal administration of DAGO selective mu-agonist, n = 28), morphine (less selective mu-agonist, n = 22), DPDPE (selective delta-agonist, n = 25), and DADL (less selective delta-agonist, n = 17) produced statistically significant suppression of noxiously evoked activity in a time- and dose-dependent manner. In addition, intravenously administered naloxone (nonselective opiate antagonist) reversed the suppressive effects of all opiates studied. Intravenously administered ICI 174,864 (selective delta-antagonist) reversed the effects of DPDPE. These results, based on relative selectivity for opiate receptors, indicate that both mu- and delta-opiate receptors can modulate the input of nociceptive information in the spinal dorsal horn. To study interactions between mu- and delta-receptors at the level of the spinal cord, a combination of the above agonists was injected intrathecally--namely, an ineffective or slightly effective dose of DAGO (1 or 1.5 micrograms, respectively) that was combined with an ineffective dose of DPDPE (30 micrograms). The intrathecal combination of DAGO and DPDPE produced significant synergistic suppressive effects of noxiously evoked activity. These findings, again based on relative selectivity, suggest that drug combinations that include both selective mu- and delta-agonists may be a useful method of lowering the total amount of any one drug, thus decreasing the likelihood of side effects, while at the same time producing significant analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics, Opioid

Intrathecal clonidine suppresses noxiously evoked activity of spinal wide dynamic range neurons in cats.

The analgesic effectiveness of perispinal clonidine administration prompted us to evaluate clonidine effects on spinal dorsal horn wide dynamic range neurons. Intrathecal clonidine produced a dose-dependent (10 and 30 micrograms), yohimbine-reversible suppression of noxiously evoked activity in decerebrate, spinal cord-transected cats. In addition, combining ineffective intrathecal doses of morphine (25 micrograms) and clonidine (5 micrograms) produced statistically significant, reversible suppression of noxiously evoked activity. The time course of suppression was similar to that observed behaviorally. These results support the role of spinal alpha 2-adrenergic receptors in clonidine analgesia.

Analgesics

A kinetic study on chlorpromazine disposition and hypothermic response in rats.

Pharmacokinetic relationships were developed to characterize a multi-exponential drug disposition and pharmacologic response time courses. The derived expressions were applied to serum and cerebral concentrations and the hypothermic response data, which were obtained after rapid intravenous administration of chlorpromazine hydrochloride to rats. The results of this study indicate that the magnitude of the pharmacologic effects of chlorpromazine such as decrease in metabolic heat production and increase in tail blood flow, at a given time, are logarithmic logistic functions of the cerebral chlorpromazine concentration at that time.

Animals

Inhibitory effect of methylated derivatives of guanylic acid for protein synthesis with reference to the functional structure of the 5'-'cap' in viral messenger RNA.

Guanylic acid modified variously with methyl groups on base or sugar moieties were synthesized chemically and their inhibitory effects on protein synthesis were tesetd in a wheat germ cell-free system using mRNAs from cytoplasmic polyhedrosis virus and tobacco mosaic virus. The confronting dinucleotide m7G5' pppA that corresponds to the most simple 'cap' structure of an eukaryotic mRNA is a strong inhibitor of protein synthesis, but non-methylated G5' pppA or G5' ppA is not inhibitory. The strong inhibitory effect is observed only by 7-methylguanylic acid (pm7G). Among 11 derivatives of pG, the most effective inhibitors are methylated at the 7-position. Further methylation at the other position sometimes cancels the inhibitory effect. Although pm7G carries a positively charged base, other nucleotides which carry a plus charged base (1-methyladenylic acid and 2-methylthio-7-methylinosinic acid) were not inhibitory. Thus, methylation at the 7-position on guanylic acid is specifically required for the inhibitory effect. Addition of pm7G was inhibitory for the formation of the initiation complex for eukaryotic protein synthesis. These results suggest that the 'cap' component containing 7-methylguanylic acid in viral mRNA participates during protein synthesis, especially in its initial steps. Protein synthesis in a bacterial cell-free system was not inhibited by addition of m7GpppA or pm7G when either TMV RNA or phage MS2 RNA was used as an mRNA.

Guanine Nucleotides

Effects of excess intake of leucine and valine deficiency on tryptophan and niacin metabolites in humans.

Nineteen healthy humans (2 men and 17 women) served as experimental subjects in 4 experiments using diets having different levels of leucine and also a valine-deficient diet. The effect of an excess intake of leucine, with and without addition of vitamin B-6, and the effect of a deficiency of valine on urinary excretions of N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, nicotinic acid, quinolinic acid, and 5-hydroxyindole acetic acid, and on the level of plasma amino acids were investigated. There was no effect of leucine on the excretion of these metabolites, but a marked decrease in the plasma (or serum) valine level was observed. The same decrease was seen when a valine-deficient diet was fed.

Adult

Protein nutrition and aging.

Twenty-four female rats consisting of 6 sets of litters were used for the experiment. After weaning, rats were divided into 4 groups and fed with 10, 18, 27 and 36% casein diet. Effect of protein nutrition on aging was examined from the anthropometric and biochemical viewpoint. The difference of growth in body weight, and that of the urinary excretion of creatinine and 17-ketosteroids observed in the early period of growing disappeared by the end of growth period. From 1 year after birth, serum alkaline phosphatase activity and serum cholesterol were also measured. However, effect of protein nutrition on these parameters was not clear due to the scatter of data. The difference in diet did not affect life span in the present experiments, but the effect of the variance of litters on it seemed to be significant between the rats fed 18% casein diet and those fed 10% casein diet. Rats fed high-protein diet had a great number of lesions in the kidney and hypophysis, and often an incidence of tumors.

17-Ketosteroids