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Biomedical subjects

M Sasa

Publications and source records attributed to M Sasa.

At least 163 records · Page 9Linked to original sources

Chemoendocrine therapy in DMBA-induced rat mammary carcinoma.

In the present study, chemotherapy with 5-fluorouracil(5-Fu), endocrine therapy with tamoxifen (TAM), and chemoendocrine therapy with concominant use of 5-FU and TAM were performed and compared for DMBA-induced rat mammary carcinoma, a hormone-dependent tumor. The study was designed to assess the usefulness of chemoendorine therapy based on the antitumor effects and changes in hormone receptor levels. The response rates in the groups treated with 5-Fu or TAM alone and the combination of 5-Fu and TAM were 60%, 50% and 62%, respectively. There was no difference in these response rates. The tumor regression rates in these treatment groups were 22 +/- 69%, 20 +/- 54% and 46 +/- 37%; again there was no difference among the three groups. After treatment, the estrogen receptor (ER) and progesterone receptor (PgR) levels decreased significantly in the groups treated with TAM alone and the combination of 5-FU and TAM but remained unchanged in the group treated with 5-FU alone. The decreases in the ER and PgR levels in responsive tumors after treatment were considerably greater in the groups greated with TAM alone and the combination of 5-FU and TAM than in the group treated with 5-FU alone. However, the changes in the receptor levels in nonresponsive tumors did not differ among the three treatment groups. Moreover, there were no differences in the antitumor effects and changes in receptor levels between the groups treated with TAM alone and the combination of 5-FU and TAM. These results suggest that the antitumor effect observed in the combination therapy with 5-FU and TAM was mainly due to the action of TAM. In brief, the expected additive effects of chemoendocrine therapy were not observed.

9,10-Dimethyl-1,2-benzanthracene↗

Voltage and current clamp studies of muscarinic and nicotinic excitation of the rat adrenal chromaffin cells.

Characteristics of the muscarinic and nicotinic excitation of chromaffin cells that had been freshly isolated from the rat adrenal medullae were analyzed using voltage and current clamp techniques. A dose-dependent increase in the extracellularly recorded firing of cells was observed when 10(-6) to 10(-4) M acetylcholine (ACh) were locally applied to the cells in the vicinity of the target cell being recorded using a microinflow method. During voltage clamp recording at the resting membrane potential, ACh induced two different sequential inward currents: a transient current with a rapid rising phase (fast response) and an apparent inward current with a slow rising phase (slow response). The membrane conductance increased during the ACh-induced fast response, and it subsequently decreased during the slow response. The amplitude of the fast response decreased when the holding potential was shifted to depolarized levels, whereas the amplitude of the slow response increased with depolarization. Nicotine produced fast depolarization and a transient inward current that was reduced by the membrane depolarization. In contrast, muscarine induced a slow depolarization and an apparent inward current that increased with depolarization. Muscarine also reduced the inward K+ current that had been induced by the application of a high K+ medium to the outside of the cell at the resting membrane potential. It is suggested that muscarinic excitation is triggered by the suppression of K+ channels that are open at potentials near the resting membrane potential. The present results indicate that ACh-induced excitation of adrenal chromaffin cells involves two separate mechanisms mediated by nicotinic and muscarinic receptors.

Acetylcholine↗

A patch clamp study of muscarinic excitation of the rat adrenal chromaffin cells.

A patch clamp study was performed to determine the ionic mechanisms underlying the muscarinic excitation of rat adrenal chromaffin cells. Burst-like, single-channel currents with brief openings were recorded during cell-attached or cell-free patch recording when the pipette solution contained high K+ media (70-140 mM), and the currents were recorded at potentials near the resting membrane potential. The amplitude and frequency of channel openings were dependent on the membrane potential and the K+ concentration of the external medium. Moreover, the single-channel currents observed with high K+ outside the membrane during inside-out recording were suppressed by the addition of a K+ channel blocker, tetraethylammonium, inside the membrane. These results suggest that the single K+ currents recorded in the present study had properties similar to those of the resting or muscarine-activated K+ currents in atrioventricular cells of the rabbit heart. During cell-attached patch recording with the high K+ medium in the recording pipette, muscarine at concentrations of 10(-5) to 10(-4) M dose dependently decreased the frequency of the channel openings but did not affect the current-voltage relationship or the time constants of open and close time histograms. These results indicate that muscarinic-induced suppression of K+ currents is caused by a decrease in the number of active K+ channels at the resting membrane potential.

Animals↗

Studies on the chironomid midges (Diptera, Chironomidae) of the Nansei Islands, southern Japan.

The Nansei Islands are located in the subtropical zone of the western Pacific Ocean between Kyushu and Taiwan, and are composed of the two main island groups, the Amami and the Ryukyu Archipelagoes. This area has been known for the presence of a number of indigenous animal species. Prior to the present studies, collections of the chironomids mainly in the urban areas of the three main islands of the Ryukyus were carried out by Sasa and Hasegawa, and a total of 42 species, including 25 new species, were recorded. Additional collections of the chironomids mainly in the mountainous areas of this region were carried out by the present author during 1988 and 1989, and a total of 26 species (including 12 new species) were recorded from Amami Island, and a total of 27 species (including 10 new species) were recorded from the Ryukyu Islands. Eight species among them, including 3 new species, were common to the two archipelagos.

Animals↗

[Radiation-induced malignant skin tumors in the hands of five doctors].

Radiation-induced malignant skin tumors in the hands in 3 surgeons, one physician, and one dentist are reported. The latent period of the irradiation ranged between 16 years and 34 years. Clinically, small keratotic lesions were seen in 4 doctors and a large tumor the remaining doctor. On histological examination, one of the tumors was a squamous cell carcinoma, 3 were carcinomas in situ, and the fifth was a basal cell carcinoma with a squamous cell carcinoma. While the occupational hazard of developing malignant skin tumors following irradiation have decreased recently, this paper emphasizes precautions should be taken when diagnosing and caring for cancer patients.

Adult↗

Muscarinic regulation of spontaneously active medial vestibular neurons in vitro.

We examined the effects of cholinergic agonists and antagonists on spontaneously occurring action potentials extracellularly recorded from medial vestibular nucleus (MVN) neurons in rat brainstem slice preparation to elucidate the cholinergic mechanism involved in excitation. Addition of carbachol (10(-6)-10(-5) M) and muscarine (10(-6)-10(-5) M) into the bath dose-dependently increased the spontaneous firing rate, while nicotine (10(-5)-10(-4) M) had no effects. Acetylcholine (10(-6)-10(-5) M) in the presence of physostigmine (10(-7) M) also increased the firing rate in a dose-dependent manner. Conversely, atropine (10(-8)-3 x 10(-7) M) slightly decreased the firing and dose-dependently inhibited the carbachol-induced increase in the firing rate. These results suggest that the firing rate of spontaneously active MVN neurons are regulated by acetylcholine via muscarinic receptors.

Acetylcholine↗

Ethanol potentiates the effect of gamma-aminobutyric acid on medial vestibular nucleus neurons responding to horizontal rotation.

Electrophysiological studies were performed to determine whether or not ethanol potentiates the inhibitory effects of gamma-aminobutyric acid (GABA) on medial vestibular nucleus (MVN) neurons responding to horizontal sinusoidal rotation using alpha-chloralose anesthetized cats. The MVN neurons were classified into types I, II, III and IV neurons according to the responses to the horizontal rotation of the animal placed on the turntable in directions ipsilateral and contralateral to the recording site. In addition, the effects of ethanol and GABA on type I neurons were also examined. Micro-osmotic application of ethanol up to 100 nA did not affect the spontaneous firing or the rotation-induced increase in firing of type I neurons. However, the inhibitory effects of GABA up to 50 nA on the rotation-induced increase in firing were potentiated during simultaneous application of ethanol up to 100 nA. This potentiated inhibition was blocked by iontophoretic application of bicuculline (25-150 nA) and picrotoxin (45-150 nA). These results suggest that ethanol potentiates the inhibitory effects of GABA on MVN type I neurons by acting on the GABA receptor and/or receptor-coupled chloride ion channel.

Animals↗

Ventral tegmental area-mediated inhibition of neurons of the nucleus accumbens receiving input from the parafascicular nucleus of the thalamus is mediated by dopamine D1 receptors.

Microiontophoretic experiments were performed to determine whether inhibition mediated by the ventral tegmental area neurons of the nucleus accumbens, receiving input from the parafascicular nucleus of thalamus, is mediated by dopamine D1 or D2 receptors, using rats anesthetized with chloral hydrate. Spikes, elicited by test stimuli applied to the parafascicular nucleus were inhibited by conditioning stimuli to the ventral tegmental area, given 30 msec before the test stimuli. This inhibition was antagonized by iontophoretic application of SCH 23390, a D1 antagonist, in 18 of 25 neurons of the nucleus accumbens, but in only 3 of 22 neurons of the nucleus accumbens during application of domperidone, a D2 antagonist. The reduction by conditioning stimulation of the ventral tegmental area of the mean number of spikes of the 25 neurons upon stimulation of the parafascicular nucleus, was abolished by SCH 23390. In contrast, domperidone did not affect the mean number of spikes of the 22 neurons upon stimulation of the parafascicular nucleus in the presence of conditioning stimulation of the ventral tegmental area. In addition, spikes elicited by stimulation of the parafascicular nucleus were dose-dependently inhibited by iontophoretic application of both SKF 38393, a D1 agonist and bromocriptine, a D2 agonist. These results suggest that inhibition by dopamine, derived from the ventral tegmental area of neurons of the nucleus accumbens, receiving input from the parafascicular nucleus, is mediated mainly by dopamine D1 receptors, although both D1 and D2 receptors are expressed on the same neuron of the nucleus accumbens, which is also inhibited by exogenously applied D2 agonists.

Animals↗

[Electroencephalographic study on the central action of a new anxiolytic: 3a alpha, 4 beta, 7 beta, 7a alpha-hexahydro-2-(4-(4-(2-pyrimidinyl)-1- piperazinyl)-butyl)-4, 7-methano-1H-isoindole-1, 3(2H)-dione dihydrogen citrate (SM-3997)].

Electroencephalographic (EEG) studies were performed to examine the effects of SM-3997 on the spontaneous EEG, EEG arousal responses, recruiting responses and hippocampal afterdischarges in rabbits and the spontaneous EEG in chronically electrode-implanted rats. In acute experiments using rabbits, SM-3997 at doses of 1-3 mg/kg, i.v., produced low-voltage fast waves in cortical EEG and slow waves with reduction of the amplitude in hippocampal EEG. The drug at doses of 1-3 mg/kg, i.v., dose-dependently inhibited the threshold stimulus voltages in EEG arousal responses induced by stimulation of the midbrain reticular formation and slightly inhibited the threshold in recruiting responses by stimulation of the centromedian nucleus of the thalamus. However, the cortical and hippocampal afterdischarges induced by hippocampal stimulation remained unaffected by SM-3997 at doses up to 3 mg/kg, i.v., while they were inhibited by diazepam of 1 mg/kg, i.v. In the study using rats in which electrodes were chronically implanted, SM-3997 at doses of 10-30 mg/kg, i.p., also produced low voltage fast waves in cortical EEG and slow waves of reduced amplitude in hippocampal EEG; and it simultaneously caused flat body posture. These results suggest that SM-3997 acts on both the cerebral cortex and hippocampus, inducing much more pronounced inhibition on the midbrain reticular formation-hippocampal system

Animals↗

Ethanol inhibits vestibular and caloric nystagmus without affecting optokinetic nystagmus in rabbits.

Effects of ethanol on optokinetic, vestibular and caloric nystagmus were investigated in pigmented rabbits to determine whether or not it affects a specific site involved in the induction of various nystagmus. Optokinetic nystagmus was produced by rotation of the drum with vertical stripes at an angular velocity of 0.85 degrees/sec. Vestibular nystagmus was induced by horizontal rotation at an angular velocity of 30 degrees/sec and caloric nystagmus by infusion of cold water into the external meatus. Cumulative injection of ethanol into the auricular vein to doses of 0.1, 0.2, 0.4 and 0.8 g/kg inhibited both vestibular and caloric nystagmus dose-dependently, but did not affect the optokinetic nystagmus. These results suggest that relatively low doses of ethanol mainly act on the peripheral vestibular organ and impair the vestibular function without affecting the optokinetic system.

Animals↗

Chironomidae as a cause of IgE-mediated histamine release in patients with asthma.

The present study was undertaken to assess the importance of Chironomidae as an allergen causing bronchial asthma in Japan, and to evaluate histamine release as an allergy test in chironomid-midge allergic patients. Extracts of Chironomidae (T. akamusi and C. Yoshimatsui) caused the release of histamine in six out of 13 allergic patients with positive skin tests. In contrast, histamine release induced by these allergens was not observed in leukocytes from two asthmatic patients and five control subjects without IgE antibody as evidenced by negative skin tests and RAST. There was a significant correlation between maximal histamine release and IgE antibody levels. Furthermore, a significant inverse relationship between the concentration of allergen causing 25% histamine release (HR25) and IgE antibody levels was observed. The correlation coefficients, however, between histamine release and RAST were not high, and there were discrepancies between the two tests in some cases. These results suggest that Chironomidae induce histamine release from leukocytes via IgE-mediated mechanism but histamine release cannot be replaced by RAST and also suggest that chironomid midge is one of the important allergens in Japan.

Allergens↗

Allergenicity of Chironomidae in asthmatic patients.

In order to clarify the relation between asthma and Chironomidae, we examined the cross-reactivity between Chironomidae and other common allergens. We noted significant correlations between positive skin tests with Chironomidae and with other allergens. The radioallergosorbent inhibition test, however, suggested that there may be no cross-reactivity or, if any, only very low cross-reactivity between midge allergens and mite, house dust (HD), silk, shrimp, or mosquito allergens.

Allergens↗

[Allergen tests with midge allergens in Moriyama City, located on the south coast of Lake Biwa].

The main species of midge which emerge from the Lake Biwa, the biggest lake in Japan, are Tokunagayusurika akamusi (TA) and Chironomus pulmons. In order to determine how the existence of Lake Biwa affects the positivity to allergen tests with midge allergens, randomly selected asthmatic patients were examined by skin test and RAST. Out of 129 patients, 35 (27%) were positive to scratch tests with an extract of Chironomus yoshimatsui (CY). Out of 64 patients, 16 (25%) were positive to TA RAST and 12 (19%) were positive to CY RAST. The positive rate of skin tests was highest in the patients aged between 20 and 39. The positive rate of TA RAST was not significantly higher than the rates reported in other districts of Japan.

Adolescent↗

The role of extraocular proprioception in vestibulo-ocular reflex of rabbits.

This study was undertaken to elucidate the role of extraocular proprioception in the vestibulo-ocular reflex, using pigmented rabbits. The presence of extraocular afferent projections in the ophthalmic branch (OB) of the trigeminal nerve was confirmed by retrograde transport of horseradish peroxidase. The OB of the left trigeminal nerve was transected at its junction with the trigeminal ganglion. Vestibular nystagmus was produced by rotating the animal clockwise and counter-clockwise in the horizontal plane in a dark room. The number and direction of the quick phase of nystagmus induced by rotation in the eye on the operated side were not different from those in the eye on the unoperated side or from those before the transection. However, the eye on the operated side moved slowly and unstably without directional preponderance during and after rotation at an angular velocity of 30 degrees/sec. In the sham-operated and unoperated groups, when the angular velocity was increased to over 90 degrees/sec, the eyes deviated in the anticompensatory direction to the head movement (the same direction as the head movement) during and immediately after the rotation. At an angular velocity of over 30 degrees/sec, however, the eye on the operated side exhibited anticompensatory response more frequently and markedly than that on the unoperated side. These results suggest that extraocular proprioception is important for fixation of the eye position in spacial relation to the head, and that loss of the sensation readily induces anticompensatory oculomotor response to head movement.

Animals↗

Electrophysiological evidence for cholinoceptive neurons in the medial vestibular nucleus: studies on rat brain stem in vitro.

Electrophysiological studies were performed to determine whether or not cholinoceptive neurons are present in the rat medial vestibular nucleus (MVN) using brainstem slice preparations. Fifty-three MVN neurons, whose activities were extracellularly recorded, fired spikes spontaneously and regularly with an interspike interval of 180 +/- 27 ms (mean +/- S.E.M.) and a coefficient of variation of 0.11 +/- 0.02. Intracellularly recorded neurons also exhibited similar spontaneous and regular generation of action potentials. Carbachol dose-dependently increased the spontaneous firing, although the firing rate was decreased in a few neurons. The addition of atropine reduced the firing rate, and dose-dependently attenuated the carbachol-induced excitation of the neurons. In a low Ca2+ and high Mg2+ medium, carbachol also increased the firing rate. These results indicate that the MVN contains neurons with spontaneous and regular firing, and that the excitability of these neurons is regulated by a cholinergic muscarinic mechanism.

Animals↗

Presynaptic inhibition of excitatory input from the substantia nigra to caudate nucleus neurons by a substituted quinolinone derivative, 7-[3-(4-(2,3-dimethylphenyl)piperazinyl)propoxy]-2(1H)-quinolinone (OPC-4392).

The effects of a newly synthesized quinolinone derivative, 7-[3-(4-(2,3-dimethylphenyl)piperazinyl) propoxy]-2(1H)-quinolinone (OPC-4392) on neuronal activities of the caudate nucleus (CN) were investigated in cats anesthetized with alpha-chloralose using a microiontophoretic method. In the CN neurons of which spikes elicited by stimulation of the pars compacta of substantia nigra (SN) were suppressed by iontophoretically applied domperidone, a dopamine D-2 receptor antagonist, application of OPC-4392 (100-200 nA) inhibited the spike generation induced by SN stimulation. Conversely, the CN neurons insensitive to domperidone were unaffected by OPC-4392. Iontophoretic application of CPC-4392 up to 200 nA did not affect glutamate-induced firing of the CN neurons, of which the firing was blocked by dopamine less than 100 nA. In addition, OPC-4392 did not inhibit firing induced by bromocriptine, a dopamine D-2 agonist; while domperidone suppressed the bromocriptine-induced firing without affecting the glutamate-induced firing. These results suggest that OPC-4392 acts on the dopaminergic nerve terminals and inhibits excitatory transmission from the SN to the CN.

Action Potentials↗

Contraction of urinary bladder by central norepinephrine originating in the locus coeruleus.

Studies were performed to elucidate the role of the locus coeruleus, which is rich in norepinephrine-containing cell bodies, in vesical function using alpha-chloralose anesthetized cats. Stimulation of the locus coeruleus caused contraction of the urinary bladder, which was not affected by transection of the bilateral hypogastric nerves, but blocked by intravenous administration of hexamethonium, a ganglion blocking agent. In animals with transected hypogastric nerves, the locus coeruleus-induced contraction was inhibited by intrathecal administration of phentolamine (alpha-blocker) and prazosin (alpha 1-blocker), but not affected by intrathecal sotalol (beta-blocker) or yohimbine (alpha 2-blocker). In animals treated with reserpine, the locus coeruleus-induced contraction was enhanced by intravenous application of L-dopa, a precursor of norepinephrine. These results suggest that norepinephrine derived from the locus coeruleus activated preganglionic neurons in the sacral intermediolateral nuclei via alpha 1-receptors, thereby producing urinary bladder contraction.

Animals↗

Survival and blood flow evaluation of canine venous flaps.

Using a canine model, we compared postoperative viability of saphenous venous flaps, cephalic venous flaps, and composite-tissue grafts without vascular connections. Of the saphenous flaps, 14 percent survived. Of the flaps based on the cephalic vein, 75 percent survived. Cephalic composite-tissue grafts were 13 percent successful. The presence of a more intricate venous plexus in a flap seems to increase its chances of success. Arterial injections of radioisotope-labeled microspheres were used to chart revascularization in cephalic flaps. These flaps demonstrated arterial blood flow by day 3, while the composite grafts showed no flow until day 7. Venous injections of microspheres distal to the flap were used to test vein-to-capillary blood flow. No significant entrapment of microspheres within the flaps occurred at any time, suggesting such flow to be inadequate.

Animals↗