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Biomedical subjects

J Yano

Publications and source records attributed to J Yano.

At least 19 recordsLinked to original sources

Actions of cholinergic agonists and antagonists on the efferent synapse in the frog sacculus.

Intracellular recordings were made from hair cells in the frog saccular epithelium isolated with its innervating nerves. Inhibitory post-synaptic potentials (IPSPs) were recorded from hair cells when the efferent fibers were activated by electrical stimulation. The effects of acetylcholine (ACh), cholinomimetics, and cholinergic antagonists on the efferent synapse were studied in a preparation where the IPSPs can be observed directly. ACh or carbachol (CCh) produced a transient membrane hyperpolarization with a decrease in input resistance followed by an abolition or reduction of the IPSP. In a low Ca2+ medium where efferent synaptic activity was abolished, ACh or CCh still induced hyperpolarization, though the response appeared to be smaller than that in normal medium. Neither nicotinic (dimethyl-4-phenyl-piperazinium (DMPP), phenyltrimethylammonium (PTMA) and nicotine) nor muscarinic (muscarine, methacholine, bethanechol and oxotremorine) agonists induced the membrane hyperpolarization, but the former drugs inhibited the IPSPs while the latter drugs did not. Both d-tubocurarine and atropine inhibited the IPSP, but the d-tubocurarine was more potent, causing inhibition even at a dose of 0.5 microM while 2 microM or more atropine was needed. The ACh- or CCh-induced hyperpolarization was inhibited completely by d-tubocurarine (5 microM), but only slightly by atropine (5 microM). These results may indicate that the IPSP and the effects of ACh or CCh are based on a direct interaction between ACh or CCh and ACh receptors on the hair cells.

Acetylcholine

Somatotopic organization and columnar structure of vibrissae representation in the rat ventrobasal complex.

The region of vibrissae representation in the ventrobasal complex (VB) of the rat was systematically mapped, based on receptive fields of many single neurons. Results showed that the ventralmost row of vibrissae projected to the rostral part of VB, that the dorsal-most row projected to the caudal part, and that the caudalmost vibrissae of each row projected to the most dorsolateral part of VB and more rostral vibrissae to the more ventromedial part. Further, it was revealed that the clusters of neurons receiving projections from any individual vibrissae formed corresponding columns extending from the anterodorsomedial to the posteroventrolateral direction, and that these columns piled up dorsoventrally and anteroposteriorly, with ventral ones shifted progressively medially. When cross sections of these columns were viewed on an oblique horizontal section of VB, a group of columns corresponding to each row lined up from the dorsolateral to the ventromedial direction with a rostral convexity, which means that the third or fourth vibrissa in each row projected most rostrally in that row. These results confirmed previous physiological mapping studies of vibrissal representation and are in good agreement with anatomical studies on barreloid structure in VB.

Animals

Observations of the sensing and the tectorial membrane in bullfrog amphibian papilla: their possible functional roles.

Three dimensional reconstructions of the amphibian papilla were performed with light microscopic observations, mainly for the sensing membrane (SM). In horizontal sections of the papilla, the anteromedial end of the SM, which makes contact with the massive anterior portion of the tectorial membrane (TM), is several times thicker than the posterolateral end close to the column of the innervating nerves. This gradient of thickness is observed in all the sections from the dorsal portion attached to the TM to the ventral floor of the papilla. The SM connects to the TM in a topological manner; the anteromedial portion of the TM relates to the anterior end of the SM and the anterolateral and the middle portions of the TM correspond to the sites shifting posteriorly on the SM. The morphology of the SM and its manner of connection to the TM suggest that the SM plays important roles in the occurrence of frequency selectivity and of tonotopic organization of the amphibian papilla.

Animals

Does reperfusion extend necrosis? A study in a single territory of myocardial ischemia--half reperfused and half not reperfused.

The purpose of this study was to confirm or disprove the existence of reperfusion-induced extension of necrosis. To avoid the effect of the variability of collateral circulation when groups of dogs are compared, we compared the effect of reperfusion and nonreperfusion on myocardial necrosis in a single ischemic territory, half of which was reperfused and half of which was not. The left anterior descending coronary artery (LAD) territory between its last diagonal branch and the apex was studied because it was found to have uniform collateral blood flow. In 20 dogs, the LAD was occluded for 90-240 minutes to produce necrosis of different degrees of transmurality. Before release of this occlusion, the LAD was occluded distally halfway to the apex to keep the distal half nonreperfused. After 5 minutes of proximal reperfusion. Monastral blue dye was injected into the left atrium for demarcation of the reperfused region, and the heart was arrested, excised, cut parallel to the LAD, and placed into triphenyl tetrazolium chloride (TTC) solution for delineation of the region of necrosis. The validity of TTC staining under the conditions of this study was confirmed by light and electron microscopy. The transmurality of necrosis, measured within 1 or 0.5 cm on either side of the boundary, ranged from 30% to 88% of wall thickness and was not different in the reperfused compared with the nonreperfused region (paired t test). Reperfusion did not advance the epicardial edge of necrosis compared with the nonreperfused region. In conclusion, at 5 minutes after reperfusion, comparison of necrosis in the reperfused and nonreperfused halves of a single ischemic territory could not demonstrate an extension of necrosis by reperfusion.

Animals

Selective decrease in lysis of old thrombi after rapid administration of tissue-type plasminogen activator.

The safety of thrombolytic therapy of acute myocardial infarction could be improved if a method were developed to dissolve fresh occlusive coronary thrombus without simultaneously dissolving hemostatic thrombi outside the coronary arteries. This study is based on the assumption that, in a patient with evolving acute myocardial infarction, hemostatic thrombi are likely to be older than the thrombus responsible for occlusion of the coronary artery. It explored whether the relative rates of lysis of fresh and old thrombi could be influenced by the rapidity of recombinant tissue-type plasminogen activator (rt-PA) administration. In each of 17 dogs, two 1 h and two 24 h old thrombi were produced by inserting copper coils into both jugular and both femoral veins. After 24 h and 1 h, respectively, the coils with the thrombi were removed, weighed and inserted into the adjacent carotid and femoral arteries. A 1 mg/kg body weight dose of rt-PA was given either over 180 or over 30 min. The coils were removed and weights of the residual thrombi determined at the end of the 180 min infusion (Group I), at the end of the 30 min infusion (Group IIA) and 45 min after the 30 min infusion (Group IIB). The 24 h old thrombi were lysed significantly less than the 1 h old thrombi in all three experimental groups: 53.9 +/- 4.8% (mean +/- SE) versus 86.1 +/- 2.5% in Group I (p less than 0.001), 16.6 +/- 3.5% versus 65.2 +/- 6.0% in Group IIA (p less than 0.001) and 21.6 +/- 5.4% versus 91.7 +/- 1.7% in Group IIB (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Acute toxicity studies of miporamicin and its degradation products and metabolites in the mouse and rat].

Acute toxicity studies of miporamicin and its trace ingredients, degradations and metabolites were conducted in mice and rats. 1. Following oral administration of miporamicin (MPM), none died among mice or rats even at the highest dosage levels. Therefore, its LD50 values were estimated to be greater than 2,500 mg/kg for mice and greater than 2,000 mg/kg for rats. The LD50 value of MPM was the highest by oral route, followed, in order, by subcutaneous route and intravenous route. There was no difference in this respect between sexes of animals studied. 2. No signs of abnormalities were observed among mice or rats following oral administration of MPM. In animals dosed with MPM by subcutaneous route, such inflammatory reactions as swelling, subcutaneous hyperemia and hemorrhage, and loss of hair incrustation at the site of injection were noted. Animals among those given MPM by intravenous injection developed postdosing depression of motor activity, respiratory depression or arrest, tremor and convulsion. 3. Deaths from administration of MPM were estimated to be due to paralysis of respiratory function inasmuch as fatally affected animals exhibited respiratory depression and cyanosis and, subsequently, respiratory arrest was followed by cardiac arrest. 4. Trace ingredients, metabolites and degradation products of MPM proved to be essentially the same as MPM in acute toxicities.

Administration, Oral

[Subacute toxicity study of miporamicin in rats by twenty-eight-day administration in feed].

A 28-day oral dosage test of miporamicin (MPM), a new macrolide antibiotic, was performed to assess its toxicologic potential in groups of male and female rats receiving the compound in feed. Five graded dosage levels of 0, 3,200, 8,000, 20,000, and 50,000 ppm were employed for treatment with MPM in feed and the treatment period was followed by a 28-day recovery phase observation period. 1. No deaths occurred throughout the course of the experiment. Animals receiving 50,000 ppm developed signs: ruffled hair coat and emaciation, which disappeared following withdrawal of the drug. 2. The MPM-50,000 group displayed depression of weight gain and decrease of feed and water intake during the treatment period. During the posttreatment recovery phase observation period the animals showed recovery in weight gain rate as well as in feed and water intake. 3. The achieved compound dosage was 273 mg/kg/day in males and 288 mg/kg/day in females in the MPM-3,200 group, 721 and 773 mg/kg/day respectively in the MPM-8,000 group, 1,738 and 1,856 mg/kg/day in the MPM-20,000 group, and 3,405 and 3,611 mg/kg/day in the MPM-50,000 group. 4. Hematological examinations revealed low values for RBC, WBC, hematocrit and hemoglobin concentration and decreased platelet counts in the MPM-50,000 group, which were considered to be due to the decreased feed intake. These changes disappeared or abated following withdrawal. 5. Of various serum biochemical parameters assessed, total protein, albumin, glucose and triglycerides showed lowered values in the MPM-50,000 group. All these changes were considered to be attributable to the decreased feed intake. During the ensuing recovery phase observation period, all these parameters showed restoration or abatement in parallel with the recovery in feed intake. 6. Urine analysis disclosed decrease of urine volume, lowered electrolyte concentration and elevation of urine osmolarity in the MPM-20,000 and the MPM-50,000 groups. These changes were considered to be secondary to cecal enlargement which is commonly seen with antibiotic medication, or to the decreased feed and water intake. Following drug withdrawal, all these changes disappeared with the recovery in feed and water intake and abatement of cecal hyperplasia. 7. At terminal necropsy, diminution of body fat and atrophy of the spleen and thymus that correlated with emaciation were noted in the MPM-50,000 group. Dose-related enlargement of the caecum was also noted in the treated groups. All these changes disappeared or abated following withdrawal.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral

[Six-month chronic toxicity study of miporamicin in rats].

A six-month oral toxicity test of the new macrolide antibiotic miporamicin (MPM) was carried out in male and female rats receiving the compound in feed at concentrations of 1,280, 3,200, 8,000, or 20,000 ppm. The animals were further observed for recovery for 2 months after the completion of the treatment period. 1. No death occurred at any dosage levels throughout the study period. The only notable signs observed were marginal blepharitis and aging-associated changes that were seen occasionally among the treated and control rats. There were no symptomatic changes of particular note. 2. Body weight, feed intake and water consumption data did not reveal any noticeable change. 3. The achieved test compound intake was 69 mg/kg/day for males and 82 mg/kg/day for females in the MPM-1,280 group, 176 mg/kg/day for males and 207 mg/kg/day for females in the MPM-3,200 group, 436 mg/kg/day for males and 519 mg/kg/day for females in the MPM-8,000 group, and 1,080 mg/kg/day for males and 1,280 mg/kg/day for females in the MPM-20,000 group. 4. No changes attributable to these treatments were noted in the hematological examination or serum biochemical tests. 5. Urinalysis disclosed mild changes with respect to urine volume, urinary electrolyte concentration and osmolarity. Animals recovered from all these changes during the recovery phase observation. 6. At gross pathologic examination a dose-related enlargement of the caecum was observed. The change disappeared or diminished following the 2-month recovery phase observation. 7. Organ weight analysis showed a dose-related increase of weight of the caecum. Animals recovered or abated in this respect during the 2-month recovery phase observation. 8. Histopathologic examination revealed no adverse toxicologic changes other than spontaneous or aging-associated ones. 9. No abnormalities were noted in the liver or in the kidneys as examined by electron microscopy. 10. The maximum non-effective level of MPM thus was estimated to be 20,000 ppm at which no organic damage occurred.

Administration, Oral

A 32-kDa protein associated with phospholipase A2-inhibitory activity from human placenta.

Two monomeric 32-kDa proteins, termed 32K-I (pI 5.8) and 32K-II (pI 5.1), were isolated from human placenta, which was solubilized by a Ca2+-chelator. Only 32K-I was associated with PLA2-inhibitory activity. CNBr peptide mapping indicated that 32K-I was distinct from 32K-II and two 36-kDa proteins, called calpactin I and II or lipocortin II and I, which have been shown to possess PLA2-inhibitory activity. 32K-I bound to PS in a Ca2+-dependent manner. 32K-I was detected in many tissues except brain, cardiac and skeletal muscle.

Enzyme Inhibitors

Ancrod enhances the thrombolytic effect of streptokinase and urokinase.

Since thrombi continue to incorporate fibrin during lysis we tested the effect of pretreatment with ancrod, a defibrinating agent from Malaysian pit viper venom, on thrombolysis with urokinase and streptokinase. Thrombi were induced by copper-coils in the carotid arteries of the dogs, weighed after 1 hour and inserted into the femoral arteries of the same animals. They were then exposed for 15 min to iv boluses of streptokinase 10,000 U/kg, urokinase 10,000 U/kg and urokinase 25,000 U/kg with or without pretreatment with ancrod. Ancrod depleted fibrinogen within 5 min and enhanced the lytic effect of streptokinase from 25 +/- 8% to 59 +/- 13% (p less than .05), urokinase 10,000 U/kg from 16 +/- 11% to 66 +/- 18% (p less than .01) and urokinase 25,000 U/kg from 27 +/- 17% to 85 +/- 8% (p less than .001) of the initial thrombus weight. Ancrod itself did not activate plasminogen to plasmin. We conclude that ancrod enhances thrombolysis probably by depleting fibrinogen and preventing new fibrin incorporation into the thrombus during lysis.

Ancrod

Influence of water quality on in vitro fertilization and embryo development for the mouse.

Mouse in vitro fertilization and embryo culture were performed in media prepared with five different water preparations. The results of the experiments improved with the frequency of distillation. Each water preparation was analyzed by the measurement of the electrical conductivities and inorganic ion concentrations and by high-performance liquid chromatography to examine the mutual relation between water quality and the method of water purification. The best results were obtained with Milli-Q water, which had the lowest concentration of inorganic ions and organic compounds. On the contrary, unexpected contamination by organic compounds and zinc ions occurred after multiple distillation, possibly leached from the glassware and silicon tube. The hatching rate seemed to be an appropriate indicator to assess the biological qualities of media for the development of embryos cultured in vitro.

Animals