Japanese Multicenter Trial of Cyclosporine in Renal Transplantation: overall results and analysis of the factors influencing graft survival rate.
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Clinical Trials as Topic↗
Biomedical subjects
H Takagi
Publications and source records attributed to H Takagi.
[Nonthyroidal illness: studies on acute viral hepatitis].
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Acute Disease↗
[Preparation of an antithrombogenic bypass-catheter of the portal vein and its application to extended radical surgery in pancreatic cancer].
The curative resectability of pancreatic cancer has been considered to be extremely low. One of the reasons for this is invasion of the pancreatic cancer cells into the portal vein, and resection of the portal vein in the usual manner would bring create various problems following acute portal vein occlusion. Sudden occlusion of the portal vein has been shown to cause profound and fatal shock in animal experiments. Now, however, with our newly developed procedure of bypassing the portal blood into the systemic circulation or intrahepatic portal vein using an antithrombogenic bypass-catheter, made from heparinized hydrophilic polymer (Toray, Anthron), combined resection of the portal vein can be performed with safety and ease. Using the catheter-bypass method, 55 pancreatectomies accompanied by portal vein resection have been safely performed, mostly in patients with pancreatic cancer. Occlusion time of the portal vein ranged from 20-302 minutes (mean, 94 minutes). No side effects of the catheter were observed. The rate of occurrence of postoperative thrombosis of the portal vein was 1.8% (1/55) and operative mortality was 7.3% (4/55). Resectability rate for pancreatic cancer was 11.2% (5/42) between 1971 and 1980, but this has been remarkably improved to over 60% (53/87) in the period between 1981 and August 1986 by the application of the catheter-bypass method. This method is recommended not only for pancreatic cancer operations but also for hepatobiliary surgery.
Catheterization↗
[Effects of chlordiazepoxide on passive avoidance learning in Wistar-Imamichi and F344/Du strain rats].
The present study was designed to investigate the effects of chlordiazepoxide (CDP; 5 and 10 mg/kg, ip) on one-trial step-through passive avoidance learning in Wistar-Imamichi (W-I) and F344/Du (F) strain rats. Step-through latency and the time spent in safety-box were significantly longer in W-I than F rats. The number of animals that attained the 300-s criterion was also larger in W-I than F rats. Therefore, it was concluded that W-I rats showed superior performance in the passive avoidance task as compared to F rats. Taken together, these and the previous results (Iwasaki et al, 1984) that F rats acquired the active avoidance learning more easily than W-I rats, the differences of performance in the two strains would reflect differences of strain-specific response patterns in aversive situations, but not of learning ability. Further, CDP produced a dose-dependent state-dependency in W-I but not in F rats. These strain differences in the effect of CDP were considered to derive from differences in sensitivity to the drug, rather than in the baseline performance level, because comparable strain differences in drug effect were reported in active avoidance learning.
Animals↗
Hydrolysis of neo-kyotorphin (Thr-Ser-Lys-Tyr-Arg) and [Met]enkephalin-Arg6-Phe7 by angiotensin-converting enzyme from monkey brain.
Angiotensin-converting enzyme (ACE; dipeptidyl carboxypeptidase, EC 3.4.15.1) from monkey brain was partially purified 274-fold with 4.5% yield. The optimum pH of the enzyme was 8.2, and its Km was 3.3 mM, with hippuryl-His-Leu as the substrate in 300 mM NaCl. Its molecular weight (Mr) was estimated to be approximately 260,000 by gel filtration on Sephadex G-200. On high-performance liquid chromatographic analysis, ACE hydrolyzed neo-kyotorphin Thr-Ser-Lys-Tyr-Arg) with liberation of kyotorphin (Tyr-Arg), the [Met]enkephalin releaser. ACE also converted [Met]enkephalin-Arg6-Phe7 to [Met]enkephalin; then the enzyme slowly hydrolyzed the resulting [Met]enkephalin. The Km values of the enzyme for neo-kyotorphin and [Met]enkephalin-Arg6-Phe7 were 0.58 and 0.30 mM respectively. Thus, brain ACE may have a role in the formation of kyotorphin and [Met]enkephalin from their precursors but has little part in [Met]enkephalin degrading processes.
Angiotensin-Converting Enzyme Inhibitors↗
Treatment for unresectable hepatoma via selective hepatic arterial infusion of lymphokine-activated killer cells generated from autologous spleen cells.
Nonspecific tumoricidal effectors, called lymphokine-activated killer (LAK) cells, can be induced from the tumor-bearer's spleen in vitro. The adoptive transfer of such LAK cells to a patient with unresectable hepatoma was performed in this study. About 2.4 X 10(9) LAK cells generated from the autologous spleen were adoptively transferred to the patient via hepatic arterial catheter. Signs of toxicity encountered with LAK cell infusions comprised chills and fever only. Chemical studies of hepatic, renal, and hematologic parameters were normal; pulmonary function studies revealed no changes after infusion. With the transfer of LAK cells, serum alpha-fetoprotein (AFP) levels were markedly decreased and ascitic fluid retention was transiently reduced. Though the therapeutic effect was transient, these trials offered hope for a new therapeutic approach to unresectable hepatoma. Further, the availability of large amounts of recombinant interleukin-2 (rIL-2) may now make widespread use of this approach possible.
Adult↗
Ultrastructural observation of nerve fibers containing both substance P and calcitonin gene-related peptide in the nucleus tractus solitarii of the rat: a combination of immunofluorescence and PAP methods.
Nerve fibers and their axon terminals with substance P (SP)-like and calcitonin gene-related peptide (CGRP)-like immunoreactivity in the nucleus tractus solitarii were ultrastructurally characterized by a combination of immunofluorescent double staining and the PAP method. The axon terminals formed asymmetrical synaptic contacts with other non-reactive neuronal elements (perikarya, dendritic shafts and dendritic spines). Some terminals received synaptic inputs from non-reactive axon terminals. This suggests that some, if not all, afferents containing SP and CGRP are affected presynaptically by other afferents.
Animals↗
Aniracetam augments, and midazolam inhibits, the long-term potentiation in guinea-pig hippocampal slices.
The effects of aniracetam, a nootropic drug, and midazolam, which produces amnesia, on the long-term potentiation (LTP) of population spikes was investigated using hippocampal slices (CA3 area) from the guinea pig. Aniracetam at concentrations of 10(-7) and 10(-8) M, but not at 10(-6) M, significantly augmented LTP. On the other hand, midazolam (10(-9) M) significantly suppressed LTP. The suppressive effect was antagonized by Ro 15-1788 (10(-8) M). Both drugs did not affect the population spikes in the absence of tetanic stimulation at those concentrations. It was suggested that in vitro application of LTP is a feasible model system for evaluating the nootropic activity of drugs.
Animals↗
Biphasic effect of phorbol myristate acetate on histamine secretion induced by compound 48/80 in rat peritoneal mast cells.
Rat peritoneal mast cells which had been preincubated with phorbol myristate acetate (PMA, 100 ng/ml) for 30 sec elicited an enhanced histamine secretion induced by a potent secretagogue, compound 48/80. But a longer (5 min) preincubation with PMA followed by the agonist-stimulation induced a suppressed histamine secretion. A 5 min-PMA-pretreatment inhibited the compound 48/80-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) in [32P]-labeled cells. PMA-treatment alone for 5 min induced an activation of Ca2+-efflux monitored by 45Ca2+. The inhibition of histamine secretion induced by a 5 min-PMA-pretreatment followed by the agonist-stimulation may partly be attributed to the decreased intracellular Ca2+ concentration, [Ca2+]i, probably due to the depressed PIP2 breakdown and enhanced Ca2+-efflux. On the other hand, a 30 sec-preincubation with PMA followed by compound 48/80-stimulation induced a slight but significant increase in histamine secretion. In this case, neither breakdown of PIP2 nor Ca2+-influx was enhanced to raise the [Ca2+]i. Although we are unable to explain the mechanism for the enhancement of histamine secretion by a short (30 sec) PMA-preincubation, these results suggest that the biphasic effects of PMA on histamine secretion are mediated by intracellular Ca2+ mobilization probably via protein kinase C activation.
Animals↗
Uptake and release of kyotorphin in rat brain synaptosomes.
Uptake and release of kyotorphin (Tyr-Arg) in rat brain synaptosomes were studied. Synthetic kyotorphin was taken up into crude synaptosomes (P2), in a temperature-dependent manner. The Km and Vmax of the uptake were 1.31 +/- 0.12 X 10(-4) M and 5.9 +/- 0.5 pmol/mg protein/min, respectively. Metabolic inhibitors such as dinitrophenol and iodoacetamide and ouabain which is known as an inhibitor of Na+ dependent uptake mechanism significantly inhibited the uptake. When the synaptosomes previously preloaded with synthetic kyotorphin at 10(-4)M were exposed to high K+ medium, kyotorphin was released in a Ca2+-dependent manner. These findings support the view that kyotorphin plays a role as neurotransmitter/neuroregulator.
Animals↗
The maitotoxin-evoked Ca2+ entry into synaptosomes is enhanced by cholera toxin.
Effects of the Gs protein-mediated adenylate cyclase facilitatory system on Ca2+ entry into synaptosomes were studied, using two specific toxins. A putative Ca2+-channel agonist, maitotoxin (MTX), increased the 45Ca2+ entry and [Ca2+]i, determined with Quin-II, into synaptosomes of the rat brainstem, which were not attenuated by nifedipine. However, another Ca2+-channel agonist, BAY K-8644 did not alter the 45Ca2+ entry nor [Ca2+]i. The MTX-induced increase of the 45Ca2+ entry was significantly enhanced by addition of dibutyryl cyclic adenosine monophosphate and by the pretreatment with cholera toxin. These findings support the view that stimulation of presynaptic receptors coupled to the Gs-adenylate cyclase system may lead to a facilitation of the release of neurotransmitters, through a cAMP dependent enhancement of the opening of the Ca2+ channels located on nerve terminals.
Adenylyl Cyclases↗
A putative met-enkephalin releaser, kyotorphin enhances intracellular Ca2+ in the synaptosomes.
Kyotorphin (Tyr-Arg) at 1 to 100 microM increased the intracellular [Ca2+]i, determined with Quin-II in the slice and the entry of 45Ca2+ entry into synaptosomes of the lower brain stem of the rat. These effects were not antagonized by nifedipine nor verapamil. However, since this dipeptide caused no changes on the membrane potentials of the synaptosomes, measured with Rhodamine 6G, it is suggested that the kyotorphin-induced increase in the [Ca2+]i may be due not to effects on the voltage dependent Ca2+ channels and Na+-Ca2+ exchange mechanisms caused by the changes of the membrane potentials, but to the specific receptor (kyotorphin receptor)-mediated mechanisms.
Animals↗
[Induction of tumoricidal effectors from the tumor-bearer's splenocytes and the prospects of their utilization for adoptive immunotherapy].
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Animals↗
Low doses of naloxone produce analgesia in the mouse brain by blocking presynaptic autoinhibition of enkephalin release.
The involvement of presynaptic autoinhibition of Met-enkephalin release in naloxone-induced analgesia was studied. In both acetic acid writhing and tail-flick tests in mice, naloxone produced biphasic effects, analgesia at very low doses (1 microgram/kg s.c. or 1 ng intracisternal) and hyperalgesia at higher doses (100 micrograms/kg s.c. or 100 ng intracisternal). Morphine at 10(-6) to 10(-5)M depressed the high K+-evoked release of Met-enkephalin from slices of the rat brainstem by 12.5-55.9% of control, while naloxone at 10(-6)M significantly enhanced the release by 80.6%. These findings strongly suggest that in the mouse brain a very low dose of naloxone produces analgesia by blocking autoinhibition of enkephalin release.
Analgesia↗
Relationships between catecholaminergic neurons and cholecystokinin-containing neurons in the caudal part of the dorsomedial medulla oblongata of the rat: light and electron microscopic observations by the 'mirror technique'.
The 'mirror technique' was used in immuno-electron microscopy to examine the synaptic relationships between neuronal structures containing catecholamines and cholecystokinin (CCK) in the caudal part of the dorsomedial medulla oblongata in the rat, using antisera against tyrosine hydroxylase and CCK. CCK-immunoreactive axon terminals made synaptic contacts with catecholaminergic neurons. Some of these catecholaminergic neurons contained CCK.
Animals↗
Pertussis toxin (IAP) enhances maitotoxin (a putative Ca2+ channel agonist)-induced Ca2+ entry into synaptosomes.
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Animals↗
Ultrastructural evidence of dopaminergic input to enkephalinergic neurons in rat neostriatum.
The synaptic relationship between neuronal structures reacting with antibodies to tyrosine hydroxylase (TH) and Leu- or Met-enkephalin (ENK) was studied by the 'mirror technique' in adjacent sections of rat neostriatum. TH-immunoreactive (TH-IR) axonal boutons surrounding the neural perikarya and proximal dendrites of ENK-immunoreactive (ENK-IR) neurons were very thin (0.1-0.4 micrograms). They contained many small clear vesicles and sometimes had symmetrical membrane specializations. This provides morphological evidence for catecholaminergic, presumably dopaminergic inputs to rat striatal enkephalin neurons.
Animals↗
Histaminergic axons in the neostriatum and cerebral cortex of the rat: a correlated light and electron microscopic immunocytochemical study using histidine decarboxylase as a marker.
Histaminergic nerve fibers and their axonal varicosities in the neostriatum and cerebral cortex were light and electronmicroscopically examined by means of peroxidase-antiperoxidase immunocytochemistry with histidine decarboxylase (HDC) as a marker. A majority of HDC-like immunoreactive axonal varicosities observed in serial thin sections for electron microscopy exhibited no synaptic contacts in either the neostriatum or cerebral cortex. The remaining small proportion of immunoreactive axonal varicosities formed synaptic contacts with non-immunoreactive dendritic shafts and spines.
Animals↗