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Biomedical subjects

N Nagano

Publications and source records attributed to N Nagano.

At least 127 records · Page 7Linked to original sources

The spinal reflex of chronic spinal rats is supersensitive to 5-HTP but not to TRH or 5-HT agonists.

The effects of thyrotropin-releasing hormone (TRH), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and L-5-hydroxytryptophan (5-HTP) were studied on the monosynaptic reflex (MSR) and the polysynaptic reflex (PSR) in acute and chronic spinal rats. Radioimmunoassay showed that while chronic spinal transection (for 2 weeks) caused the complete depletion of TRH in the ventral lumbar enlargement a certain level of TRH was maintained in the dorsal lumbar enlargement. This result suggested the existence of TRH-containing neurons in the dorsal horn other than the medullary raphe neurons descending to the spinal cord. The latency to the start of the MSR was shortened in chronic spinal rats and the amplitudes of the MSR and PSR were significantly greater than those in acute spinal rats. There was no obvious difference in the effects of TRH and 5-MeODMT on spinal reflexes of acute and of chronic spinal rats although marked supersensitivity to 5-HTP was observed in both the MSR and the PSR in chronic spinal rats. The supersensitivity to 5-HTP was considered to be due to a lack of 5-hydroxytryptamine (5-HT) uptake into 5-HT-containing nerve terminals rather than to a change in 5-HT receptors. It is suggested that TRH and 5-HT do not show any mutual requirement for each other in their effects on the spinal reflex since co-depletion of TRH and 5-HT did not change the effects of TRH and 5-MeODMT in chronic spinal rats. The coexistence of 5-HT and TRH in the descending spinal pathway is not considered to be significant for the control of spinal reflexes at the postsynaptic level.

5-Hydroxytryptophan↗

Effects of L-threo-dihydroxyphenylserine on spinal reflexes and decerebrate rigidity in rats.

1. The effects of a noradrenaline precursor, L-threo-3,4-dihydroxyphenylserine (L-DOPS), on spinal mono-(MSR) and polysynaptic reflexes (PSR) and decerebrate rigidity, were studied. 2. Although a low dose of L-DOPS (10 mg/kg, i.v.) did not affect MSR or PSR in C1 spinal rats, high doses of L-DOPS (50 and 100 mg/kg, i.v.) moderately enhanced the amplitudes of both MSR and PSR. 3. Clorgyline-HCl (1 mg/kg, i.v.), an MAO inhibitor, enhanced the excitatory effects of low-dose L-DOPS (10 mg/kg, i.v.) on both reflexes. 4. Benserazide-HCl (1 mg/kg, i.v.), an L-aromatic amino acid decarboxylase inhibitor, decreased the pressor effect, but not the stimulatory effects, of L-DOPS (100 mg/kg, i.v.) on MSR and PSR. 5. L-DOPS (300 mg/kg, i.p. or i.d.) did not affect the muscle tone of rigid hindlimbs caused by radio frequency lesioning of the midbrain. 6. These results suggest that the moderate enhancing effects of L-DOPS on MSR and PSR are due to conversion of L-DOPS to noradrenaline in the spinal cord.

Animals↗

Functional significance of subtypes of 5-HT receptors in the rat spinal reflex pathway.

1. The functional significance of subtypes of 5-hydroxytryptamine (5-HT) receptors was studied in the rat spinal reflex pathway. 2. Ketanserin had no effect on the mono- (MSR) or polysynaptic reflex (PSR) in spinal rats, but decreased the PSR in intact rats. 3. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) decreased the MSR and increased the PSR in spinal rats. 4. Ketanserin antagonized the effects of 5-MeODMT without antagonizing the effects of 8-OH-DPAT. 5. Cinanserin had similar effects to those of ketanserin. 6. These results suggest that both 5-HT1A and 5-HT2 receptors mediate MSR inhibition and PSR augmentation in the spinal reflexes of spinal rats, and that the 5-HT2 receptor has a supraspinal tonic excitatory influence on the PSR in intact rats.

5,6-Dihydroxytryptamine↗

Inhibitory effect of phencyclidine on rat spinal reflexes.

1. The effects of phencyclidine (PCP) on spinal reflexes and the excitability of motoneuron somata were studied in rats. 2. PCP decreased both the monosynaptic reflex (MSR) and the polysynaptic reflex (PSR) in spinal rats as well as in intact rats. 3. The effects of PCP were not antagonized by monoaminergic and cholinergic antagonists. 4. A low dose of PCP antagonized the PSR augmentation but not the MSR augmentation caused by N-methyl-D-aspartate (NMDA). 5. In the excitability test, PCP decreased not only the monosynaptic response but also the excitability of motoneuron somata. 6. These results suggest that the inhibitory effects of PCP on spinal reflexes are not due to mediation of the monoaminergic and cholinergic systems, but partly due to its blockade of NMDA-type receptors and also to a hyperpolarizing action or a membrane-stabilizing action on the motoneuron soma.

Animals↗

Sensitivity of spinal reflexes to TRH and 5-HT in 5,6-dihydroxytryptamine-treated rats.

Destruction of descending serotonergic nerve terminals containing thyrotropin-releasing hormone (TRH) was affected in rats by the intracisternal injection of 5,6-dihydroxytryptamine (5,6-DHT) two weeks before subsequent experiments. Although the level of TRH in the lumbar enlargement was significantly reduced in 5,6-DHT-treated rats, the effects of TRH on the monosynaptic reflex (MSR) and the polysynaptic reflex (PSR) in these rats were no different from those in control rats. MSR inhibition by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) was attenuated by 5,6-DHT treatment although there was no obvious difference in the effects of 5-MeODMT on the PSR between 5,6-DHT-treated and control rats. In 5,6-DHT-treated rats, L-5-hydroxytryptophan (5-HTP) markedly decreased the MSR and increased the PSR although the same doses of 5-HTP did not produce any effects on either the MSR or the PSR in control rats. In control rats, after administration of imipramine or clorgyline, 5-HTP produced effects similar to those observed in 5,6-DHT-treated rats. These results suggest that the supersensitivity to 5-HTP in 5,6-DHT-treated rats is due to a lack of 5-hydroxytryptamine (5-HT) uptake into 5-HT-containing nerve terminals rather than to a change in 5-HT receptors.

5,6-Dihydroxytryptamine↗

Studies on beta-lactam antibiotics. I. Synthesis and in vitro anti-pseudomonal activity of 3-isothiazole-cephalosporin derivatives.

The synthesis and in vitro activity of 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2-(2-carboxy-2- alkoxyimino)acetamido]cephalosporins with a (4-carboxy-3-hydroxy-5-isothiazolyl)thiomethyl group at the 3-position are described. These cephalosporins (9a approximately 9i) showed excellent activity against Gram-negative bacteria including beta-lactamase producing strains. The most interesting compound of the series was 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2- (2-carboxy-2-propoxyimino)acetamido]-3-cephem-4-carboxylic acid (9g, YM-13115) because of its outstanding inhibitory potency against Pseudomonas aeruginosa and highly prolonged plasma half-life in rats.

Anti-Bacterial Agents↗

Enkephalin but not morphine modulates the motor activity in the frog spinal cord in vitro.

In the isolated frog spinal cord, methionine-enkephalin (ME, up to 3 X 10(-5) M) hyperpolarized the resting ventral and dorsal root potentials. These hyperpolarizations remained even under Ca2+-free conditions. ME depressed the fast component of the electrically stimulated spinal reflex and enlarged the following depolarizing component. Morphine (10(-4) M) had no apparent ME-like effects. ME may directly and indirectly affect the motoneuron and modulate the spinal motor activity in the frog spinal cord.

Animals↗

Successful regional immunotherapy with cell-wall skeletons of BCG and Nocardia rubra against autochthonous rat tumors.

Autochthonous tumors induced by 3-methylcholanthrene (MCA) in the thigh of Fischer 344 rats were treated by nonspecific immunotherapy with cell-wall skeleton of BCG (BCG-CWS) or Nocardia rubra (N-CWS) after incomplete radiotherapy. When MCA-induced autochthonous tumors grew to 3 cm in diameter, they were resected and autografted to the contralateral thigh. When the autografted tumors reached 1 cm in diameter, they were exposed to a single irradiation with 2000 rad giving rise to complete shrinkage in 16.6% of the cases. The rates of complete shrinkage were increased to 36.4% and 58.3%, respectively, by combined regional immunotherapy with BCG-CWS or N-CWS. Furthermore, immunoprophylactic effects of BCG-CWS and N-CWS were also detected in this experimental system.

Animals↗

Nonspecific adjuvant immunotherapy of lung cancer with cell wall skeleton of Mycobacterium bovis Bacillus Calmette-Guérin.

Nonspecific adjuvant immunotherapy with Bacillus Calmette-Guérin cell wall skeleton (BCG-CWS) was given to 155 lung cancer patients. Clinical effects of the BCG-CWS treatment were estimated by comparing the survival of the BCG-CWS group with that of a historical control group on the basis of 4-year results. Significant prolongation of survival time has been observed in Clinical Stages II, III (M0) and III (M1). However, most Stage III patients who were given the BCG-CWS treatment died of cancer itself after marked prolongation of survival time. An increase in complete cure rate has been expected only in Stages I and II. Surgicopathological staging was used in resected cases. Resected cases at any stage were sensitive to treatment with BCG-CWS. Histologically, all types of lung cancer including squamous cell carcinoma, adenocarcinoma, and anaplastic carcinoma were sensitive to treatment with BCG-CWS. Intrapleural administration of BCG-CWS to patients with malignant pleurisy was effective in controlling the pleural effusion and prolonging the survival time. No serious complication has been experienced in our study.

Adenocarcinoma↗

Cytostatic activity of peripheral blood monocytes against bronchogenic carcinoma cells in patients with lung cancer.

Cytostatic acitivity of peripheral blood monocytes against cultured cell lines of bronchogenic carcinoma was examined in patients with lung cancer. Cytostatic activity in lung cancer patients with neither augmented nor suppressed as compared with that of controls such as normal healthy persons, patients with malignancies other than lung cancer, and patients with benign respiratory diseases. There was no correlation between the cytostatic activity of monocytes and the advance of clinical stages of the disease. Conventional modalities of anticancer treatments such as surgery, radiotherapy, chemotherapy, and their combination therapy had no effect on cytostatic activity of peripheral blood monocytes. However, adequate immunotherapy with nocardia rubra cell-wall skeleton augmented the cytostatic activity of peripheral blood monocytes, although adequate immunotherapy with Mycobacterium bovis BCG cell-wall skeleton had no effect.

Adenocarcinoma↗