Expression of Krev-1 and c-H-ras proto-oncogenes in the rat spinal cord and the effects of noxious stimulation.
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Aging↗
Biomedical subjects
T Murakoshi
Publications and source records attributed to T Murakoshi.
Involvement of NK1 receptors in synaptic transmission in the guinea pig coeliac ganglion.
Using intracellular recording techniques, we examined the effects of tachykinin receptor agonists and antagonists on electrophysiologically identified tonic neurons of the isolated guinea pig coeliac ganglion. In most of the tonic neurons, substance P (SP), neurokinin A (NKA) and/or senktide induced a depolarization. The effects of SP and NKA were blocked by the NK1-selective antagonist, GR71251 (5 microM), but not by the NK2-selective antagonist, L659,877 (10 microM), whereas the effect of senktide was not affected by these antagonists. The NK1-selective agonists, [Sar9,Met(O)2(11)]SP and SP methyl ester, and the NK3-selective agonist, [MePhe7]neurokinin B, also evoked depolarizations in tonic neurons. By contrast, the NK2-selective agonists, [Nle10]NKA4-10, [beta-Ala8]NKA4-10 and GR64349, at 1 microM each, did not evoke any significant depolarizing response. Repetitive electrical stimulation of the mesenteric nerves induced slow excitatory postsynaptic potentials (EPSPs) in the majority of tonic neurons, which were depressed by GR71251 (5 microM). These results suggest that NK1 and NK3 receptors but not NK2 receptors are involved in the tachykinin-induced depolarization of tonic neurons, and that the NKA-induced response is due to the activation of NK1 receptors. This study also suggests the involvement of NK1 receptors in the slow EPSPs in tonic neurons.
Animals↗
Immunoelectron microscopic study on IgA, secretory component and complement component C3 in the liver of children undergoing total parenteral nutrition through neonatal period.
To study the mechanism of the intrahepatic cholestasis observed during total parenteral nutrition (TPN) in neonates, we examined the localization of IgA, secretory component (SC) and complement component C3 (C3) in the liver in 4 patients by light and electron microscopic immunohistochemistry. In the patients who received TPN for 1 month, IgA- and SC-positive cholestasis was limited to bile canaliculi, but the integrity of both the canalicular wall and intercellular tight junction was maintained. These findings suggest that obstruction in the biliary tract develops at the canalis of Hering, causing reflux of IgA and SC into the bile canaliculi. When the duration of TPN extended beyond 6 months, the cholestasis in bile canaliculi progressed further, and degeneration of hepatocytes became more marked. Bile retained in hepatocytes occasionally contained IgA and SC. IgA- and SC-positive cholestasis also developed in the interlobular bile ducts, where no cholestasis had been observed 1 month after the beginning of TPN. SC production and SC-mediated transport of IgA, which are important functions of bile duct epithelial cells in the local immune mechanism, were impaired in association with the injury of those cells. C3 was localized not only in the hepatocellular organelles where C3 is normally observed, but also in the lumen of dilated bile canaliculi, suggesting that C3 is released from hepatocytes into bile in neonates receiving TPN and that C3 may be involved in some local immune mechanism of biliary system.
Complement C3↗
[The relationship between flow velocity waveforms of umbilical and fetal middle cerebral arteries and cord blood gas values].
Umbilical artery (UA) and fetal middle cerebral artery (MCA) flow velocity waveforms were obtained from 55 fetuses just prior to elective cesarean section at 36-39 weeks of gestation and the resistance index (RI) was calculated for each waveform. Cord blood samples were obtained from both the umbilical artery and the vein at cesarean section and the blood gas values were measured immediately. The coefficients of correlation between the cord blood gas values and the resistance indices were obtained. 1. UA-RI had a significant negative correlation with pH and Po2, and a positive correlation with Pco2. 2. MCA-RI had a significant positive correlation with pH and Po2, and a negative correlation with Pco2. 3. The UA-RI/MCA-RI ratio had a significant negative correlation with pH and Po2, and a positive correlation with Pco2. 4. The best correlation was found in the UA-RI/MCA-RI ratio, and the UA-RI, MCA-RI and UA-RI/MCA-RI ratios had a closer correlation with umbilical arterial blood gas values than with umbilical venous blood gas values. A Doppler study of fetal blood distribution would be a useful method in the noninvasive assessment of the fetal blood gas state at 36-39 weeks of gestation.
Blood Flow Velocity↗
Descending inhibition of slow spinal reflex in an in vitro preparation of the newborn rat and its possible involvement in pain control.
An isolated brainstem-spinal cord preparation of the newborn rat is described in which brainstem stimulation inhibits a spinal reflex of slow time course possibly associated with nociception. The inhibition-producing area is localized in the rostral medulla and caudal pons. Perfusion of the preparation with phentolamine or strychnine antagonizes the inhibition, suggesting the involvement of alpha-adrenergic and glycine-mediated inhibitory mechanisms. Results are discussed in relation to descending inhibition of nociception.
Animals↗
Respiratory reflexes in an isolated brainstem-lung preparation of the newborn rat: possible involvement of gamma-aminobutyric acid and glycine.
An isolated brainstem-lung preparation of the newborn rat was developed for a pharmacological study on the respiratory reflexes in vitro. Spontaneous periodic depolarizations of the ventral roots (C4-C5) were observed at a frequency of 5-15/min and regarded as the respiratory activity. This activity was transiently inhibited when the lungs were inflated by gas pressure applied to the trachea. The inhibitory response of the respiratory rhythm was markedly depressed by the application of bicuculline or strychnine to the brainstem. These results suggest that gamma-aminobutyric acid and/or glycine may be neurotransmitters in the brainstem which cause the inhibitory respiratory reflex.
Animals↗
A pharmacological study on respiratory rhythm in the isolated brainstem-spinal cord preparation of the newborn rat.
An in vitro brainstem-spinal cord preparation of the newborn rat was used to examine the effects of neurotransmitters and transmitter candidates on respiratory frequency. Spontaneous periodic depolarization of the spinal ventral roots of the 4th or 5th cervical segment was observed at a frequency of 5-15 min-1 constantly for more than 5 h. The frequency of this depolarization was monitored as an index of the respiratory frequency. An elevation of the concentration of Ca2+ or Mg2+ caused a decrease in the respiratory frequency, whereas an elevation of K+ concentration caused an increase. The frequency was also increased by a reduction of pH. The highest frequency was observed at 27-28 degrees C. Dopamine, 5-hydroxytryptamine, histamine, acetylcholine, glutamic acid, substance P, and thyrotropin releasing hormone accelerated the respiratory frequency when applied by perfusion to the brainstem, whereas noradrenaline, gamma-aminobutyric acid, glycine, and [Met5] enkephalin and [Leu5] enkephalin slowed the frequency. Experiments with antagonists suggested that the stimulant effect of acetylcholine on respiratory frequency was mediated mainly by muscarinic receptors and the depressant effect of noradrenaline was mediated by alpha-adrenoceptors.
Acetylcholine↗
[Pathology of the anomalous choledocho-pancreatic junction--action of pancreatic juice on the biliary tract].
The mechanism of action of pancreatic juice on the biliary tract was investigated in a 5-year-old girl with choledochal cyst and animal models of the anomalous choledocho-pancreatic junction produced by pancreatico-cholecystostomy in 26 dogs. The results are as follows: Pancreatic enzymes are activated when bile and pancreatic juice are mixed in the biliary tract. Successively, lysolecithin and free fatty acids are produced by hydrolysis of lecithin in bile with phospholipase A2. These substances including phospholipase A2 destroy the mucosal barrier. The initial site receiving mucosal damage appears to be the epithelial apical cell membrane. The transfer of phospholipase A2 but not amylase from the biliary tract to the blood stream was suggested by comparing enzyme activity of portal and hepatic venous blood. The presence of some mutagenic substances in the contents of the choledochal cyst was confirmed by Ames assay and Rec-assay. This suggests that activated pancreatic enzymes and successively produced harmful substances in the anomalous choledocho-pancreatic junction are responsible for not only inflammatory but positively carcinogenic action on the biliary tract. In conclusion, the anomalous choledocho-pancreatic junction requires operative separation of the bile duct from the pancreatic duct despite the presence or absence of a choledochal cyst.
Animals↗
[Late complications of Hirschsprung's disease and anorectal manometry].
In 84 patients treated with Soave-Denda method, informations of their bowel habits were obtained through a questionnaire. These patients were classified into 4 groups (A; less than 3 years, B; 3 to 6 years, C; 7 to 9 years and D; more than 10 years after the operation) and analyzed by comparing their bowel habits with those of normal children in corresponding age group. Some late complications were demonstrated although 80% of patients followed for more than 10 years had a normal bowel habit. Frequent incontinence (more than once a week) was found in 18.2% of group B and 5% of group C. No patients has incontinence in group D. Frequent soiling (more than once a week) was demonstrated in 58.8% of group B, 30% of group C and 23.1% of group D although the incidence of frequent soiling ranged from 0.5 to 2.1% in normal children of these age group. Manometry to detect a rectonal reflex was useful to evaluate anorectal function because patients who showed normal reflex had excellent bowel habits without incontinence. These unexpected high incidence of late complications indicate that postoperative training of defecation is extremely important to give normal bowel habit to the patients with Hirschsprung's disease.
Adolescent↗
Tail-pinch method in vitro and the effects of some antinociceptive compounds.
An in vitro preparation for testing antinociceptive drugs is described. The preparation consists of isolated spinal cord, spinal nerve roots and functionally connected tail of the newborn rat. Noxious pressure stimulation given to the tail induced in a lumbar ventral root a depolarizing response of 1-2 mV lasting about 15-30 s, which is referred to as tail-pinch potential. Single shock stimulation of a lumbar dorsal root induced in the ipsilateral ventral root of the same segment monosynaptic and polysynaptic reflexes, which were followed by a depolarizing response lasting ca. 20 s. The latter slow response is referred to as ipsilateral slow ventral root potential (VRP). Morphine, [Met5]enkephalin, [Leu5]enkephalin and [D-Ala2,Met5]enkephalinamide depressed both the tail-pinch potential and the ipsilateral slow VRP, but did not exert any noticeable effect on the monosynaptic and polysynaptic reflexes. The effects of morphine and enkephalins were completely abolished by naloxone. Naloxone potentiated the tail-pinch potential and the ipsilateral slow VRP in the fresh preparations which had not been exposed to opiate compounds or enkephalins, suggesting that the endogenous enkephalinergic mechanism occurs in the spinal cord and modulates the incoming nociceptive signals. The present isolated spinal cord-tail preparation will be useful for studying actions of analgesic drugs and for screening compounds for analgesic effects.
Analgesics↗
The role of the N-terminus in the active conformation of the substance P analogues.
The role of the N-terminus in the activity of substance P analogues was studied with the isolated rat spinal cord and the guinea-pig ileum. When the C-terminal Leu10 or Met11 was replaced by the D-isomer, the analogues without the N-terminal tetrapeptide were 40-100 times less potent than those with the N-terminus in both motoneuron-depolarizing and ileum-contracting actions. These results that the N-terminus may stabilize the active conformation of the substance P analogues.
Amino Acids↗
[Physical rehabilitation and nursing of patients with cervical cord injuries and severe paralysis of the shoulder and arms].
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Activities of Daily Living↗
Studies on the various causal factors related to hypercoagulability in the field of obstetrics - with special reference to the onset of DIC as viewed from the changing of kinin-kallikrein system and fibrinopeptide A.
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Blood Coagulation Disorders↗
Coagulation-fibrinolytic analysis in patients with lung cancer.
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Blood Coagulation Disorders↗
Role of dextran sulfate in urokinase therapy and evaluation of the effects by estimation of plasmin inhibitor, fibrinogenolytic degradation products, and fibrinolytic degradation products.
The present study was concerned with changes in APTT and coagulation-fibrinolytic inhibitors in 2 groups of patients receiving either UK with heparin or UK with heparin and dextran sulfate (DS). APTT just after UK treatment showed a significant prolongation in patients receiving combination treatment with DS, but contrarily a shortening in patients receiving those with DS. This result indicated the usefulness of DS combination in UK treatment. There was a marked difference between the responses of alpha 2-PI and antiplasmin to the treatment, presumably as a result of immune complex formation of the alpha 2-PI with plasmin. However, no marked difference in alpha 2-PI and AT-III existed both just after and at 24 hours after UK treatment in patients receiving UK (240,000 units) with both heparin and DS and those receiving UK (480,000 units) with heparin. Those results suggest that the dosage of UK can be reduced by combination of DS. Successful UK treatment in clinical cases resulted in a decrease of alpha 2-PI and an increase of fibrinogenolytic or fibrinolytic degradation products. For these reasons, effective UK treatment appears to require combination with DS and several treatment days under the condition with a decrease of alpha 2-PI (50%) and fibrinogenolysis with fibrinolysis, which are followed by administrations of UK.
Antithrombin III↗
[Significance of fibrinopeptide A as an indicator for coagulative analysis in thrombotic diseases].
This study was made to know the significance of fibrinopeptide A(FPA) as an indicator for coagulative analysis in thrombotic diseases. In normal control subjects (n=21), values of FPA by the radioimmunoassay were 0.5 +/- 1.4 ng/ml (mean +/- SD). In animal models, using Lyoplastin (tissue thromboplastin, n=5) or Ancrod (n=5) to piglets, plasma FPA levels elevated rapidly as a reflection of fibrin formation, and these changes of FPA were found to be most rapid and sensitive among the indicators for coagulation and fibrinolysis. In patients with thrombosis (n=32), elevated FPA levels (14.7 +/- 13.8 ng/ml) and beta-thromboglobulin (beta-TG)(86.1 +/- 65.6 ng/ml) were found. FPA levels in these patients positively correlated to beta-TG (r=0.5539, P less than 0.05) and inversely to fibrinogen (fbg) (r= -0.3622, P less than 0.05). In patients with acute myelocytic leukemia (AML, n=112), acute promyelocytic leukemia (APL, n=18) and acute lymphocytic leukemia (ALL, n=15), mean FPA levels in patients with active signs and symptoms were significantly higher (AML: 13.5 ng/ml, APL: 20.8 ng/ml, ALL: 12.4 ng/ml) than those examined during remission states (AML: 7.7 ng/ml, P less than 0.02, APL: 3.9 ng/ml, P less than 0.01, ALL: 2.7 ng/ml, P less than 0.01). FPA levels in patients with APL inversely correlated to fbg (r= -0.6399, P less than 0.01). In patients with lung cancer (n=75), mean FPA level in advanced stage (17.7 ng/ml, n=67) were significantly higher than those examined in early stage 6.5 ng/ml, n=8, P less than 0.001). In patients with acute disseminated intravascular coagulation (n=12), prolonged prothrombin time and activated partial thromboplastin time, severely reduced fbg and platelets, and remarkably elevated fibrin degradation product were found. Elevated FPA and beta-TG levels were also found (FPA: 23.5 +/- 15.0 ng/ml, beta-TG: 100.0 +/- 63.0 ng/ml). In five patients with thrombotic diseases who were treated successfully with 12500 IU of heparin per 12 hours (subcutaneous injection), plasma FPA levels were reduced to near normal levels quicker than changes of other indicators. These clinical and experimental data suggested that FPA was an useful indicator for active coagulation process.
Adult↗
Synthesis, metabolism and distribution of fibrinogen and its derivatives.
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Animals↗
Assay of heparin in plasma using a chromogenic substrate and its clinical applications.
The concentration of heparin in plasma was measured using a chromogenic substrate. It appeared that the measurement of heparin concentration in plasma was important in therapeutic control and evaluation of heparin. There was a correlation between the activated partial thromboplastin time (APTT) and heparin concentration in plasma, but since the gradients of regression line differed in each of the cases, measurement of APTT alone would give a different estimate of heparin concentration in each case. Fibrinopeptide A (FPA) is considered as the best indicator for evaluatin of therapeutic effects of heparin. Therapeutic heparin concentrations were defined as ranging from 0.2 to 1.2 IU/ml because the normalization of FPA was observed and there happened no hemorrhagic accidents in that range.
Adult↗