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91.
Spontaneous miniature glycinergic inhibitory postsynaptic currents (mIPSCs) in mechanically dissociated rat sacral dorsal commissural nucleus (SDCN) neurons attached with intact glycinergic presynaptic nerve terminals and evoked IPSCs (eIPSCs) in the slice preparation were investigated using nystatin-perforated patch and conventional whole cell recording modes under the voltage-clamp conditions. Trans-ACPD (tACPD) reversibly reduced the mIPSC frequency without affecting the mean amplitude. The effect was mimicked by a specific metabotropic glutamate receptor (mGluR) II subtype agonist, (2S, 1'S, 2'S)-2-(carboxycyclo propyl) glycine (L-CCG-I), and a specific mGluRIII subtype agonist, 2-amino-4-phosphonobutyrate (L-AP4). These inhibitory effects on mIPSC frequency were blocked by the specific antagonists for mGluRII, alpha-methyl-1-(2S, 1'S, 2'S)-2-(carboxycyclo propyl) glycine and (RS)-alpha-cyclopropyl-4-phosphonophenylglycine. In the slice preparation, eIPSC amplitude and mIPSC frequency were decreased reversibly by L-CCG-I (10(-6) M) and L-AP4 (10(-6) M). In K(+)-free or K(+)-free external solution with Ba(2+) and Cs(+), Ca(2+)-free or Cd(2+) external solution, the inhibitory effect of tACPD on mIPSC frequency was unaltered. Forskolin and 8-Br-cAMP significantly increased presynaptic glycine release, and prevented the inhibitory action of tACPD on mIPSC frequency. Sp-cAMP, however, did not prevent the inhibitory action of tACPD on mIPSC frequency. It was concluded that the activation of mGluRs inhibits glycine release by reducing the action of cAMP/PKA pathway. 相似文献
92.
Susumu Yamada Roko Kubota Kazuo Kubota Kiichi Ishiwata Tatsuo Ido 《Neuroscience letters》1990,120(2):191-193
This is the first study of micro-autoradiography (micro-ARG) for [18F]2-fluoro-2-deoxy-
-glucose ([18F]FDG). The localization of [18F]FDG was demonstrated in dendrites of neuron and also in the myelinated axon in mouse normal brain in vivo. The nucleolus was relatively free of label. The counted silver grain numbers in autoradiogram were linearly correlated to the 18F radioactivities in the specimen. The micro-ARG using positron emitting 18F is a very time-saving technique with 4 hours exposure compared with the conventional method using 3H- or 14C-labeled tracers. 相似文献
93.
Hisahiko Kubota Shutaro Katsurabayashi rew J. Moorhouse† Nobuya Murakami Hitoshi Koga Norio Akaike‡ 《The Journal of physiology》2003,551(1):263-276
The transduction mechanisms underlying presynaptic GABAB receptor-mediated inhibition of transmitter release have been characterized for a variety of synapses in the central nervous system (CNS). These studies have suggested a range of transduction mechanisms, including a role for second messengers such as protein kinases A (PKA) and C (PKC). In the present study, we have examined the intracellular signalling pathways underlying baclofen-induced inhibition of GABA release from terminals synapsing onto rat basalis of Meynert neurons using patch-clamp recordings. Baclofen, a selective GABAB receptor agonist, reversibly decreased both evoked and spontaneous, miniature, GABAergic inhibitory postsynaptic currents (eIPSCs and mIPSCs, respectively). Such baclofen actions were completely abolished by CGP55845A, a selective GABAB receptor antagonist, and by staurosporine, a non-selective PKA and PKC inhibitor. The mIPSC frequency was still decreased by baclofen even in the presence of 4 AP, a K+ channel blocker, and Cd2+ , a voltage-dependent calcium channel blocker. Pharmacological activation or inhibition of PKC activity affected basal GABA release and mildly affected the response to baclofen. Inhibition of the cAMP/PKA cascade also affected basal GABA release and, in a subset of neurons, occluded the effects of baclofen, suggesting that the GABAB receptor-mediated inhibitory action on GABA release was mediated via decreases in PKA activity. In addition, PKA inhibition occluded the effects of PKC modulation on both basal GABA release and on the response to baclofen. Our results characterize the transduction pathway of baclofen at these nucleus basalis of Maynert (nBM) synapses and show, for the first time, some cross-talk between the cAMP/PKA and PKC pathways in mammalian presynaptic nerve terminals. 相似文献
94.
95.
96.
Hino M Yamane T Ohta K Kubota H Katagami T Tatsumi N 《Rinsho byori. The Japanese journal of clinical pathology》2000,48(8):689-693
Measurement of complete blood cell count and white blood cell differentiation is an essential laboratory test and the most important screening test for hematological malignancy. Recently, several automated blood cell analyzers have been developed to improve accuracy and precision. When flag messages generated in the presence of morphological abnormalities of the samples are displayed, manual revision is necessary. In our laboratory, the manual revision rate has been 35-40%. Therefore blood cell analyzers are useful in screening for abnormalities as well as greatly reducing expensive and time-consuming manual differential procedures. In addition, automated blood cell analyzers can provide several types of useful information including the leukocyte distribution scattergram. However, most such information is not utilized in the clinical field. In the future, a total hematological analysis system will be constructed so that all information provided by automated blood cell analyzer and by manual methods are available. 相似文献
97.
98.
Histological examination of the jaw muscles of the Japanese ermine showed that 4 jaw-closing muscles have 13 muscle spindles on one side of the face. The temporal muscle has 99 muscle spindles, 68 being in the anterior vertical and 31 in the posterior horizontal belly. The masseter muscle has 33 muscle spindles, 23 being in the profound and 10 in the superficial belly. The medial pterygoid muscle has 7 muscle spindles and the zygomaticomandibular muscle contains 4 muscle spindles. The lateral pterygoid and the jaw-opening muscles have no spindles. 相似文献
99.
Conversion of highly malignant colon cancer from an aggressive to a controlled disease by oral administration of a metalloproteinase inhibitor 总被引:3,自引:0,他引:3
Zili An Xiaoen Wang Neville Willmott Surinder K. Chander Simon Tickle Andrew J. P. Docherty Andrew Mountain Andrew T. Millican Richard Morphy John R. Porter R. Ola Epemolu Tetsuro Kubota A. R. Moossa Robert M. Hoffman 《Clinical & experimental metastasis》1997,15(2):184-195
In this study, we describe the activity of CT1746, an orally-active synthetic MMP inhibitor that has a greater specificity for gelatinase A, gelatinase B and stromelysin than for interstitial collagenase and matrilysin, in a nude mouse model that better mimics the clinical development of human colon cancer. The model is constructed by surgical orthotopic implantation (SOI) of histologically-intact tissue of the metastatic human colon tumor cell line Co-3. Animals were gavaged with CT1746 twice a day at 100 mg/kg for 5 days after the SOI of Co-3 for 43 days. In this model CT1746 significantly prolonged the median survival time of the tumor-bearing animals from 51 to 78 days. Significant efficacy of CT1746 was observed on primary tumor growth (32% reduction in mean tumor area at day 36), total spread and metastasis (6/20 treated animals had no detectable spread and metastasis at autopsy compared to 100% incidence of secondaries in control groups). Efficacy of CT1746 could also be seen on reducing tumor spread and metastasis to individual organ sites such as the abdominal wall, cecum and lymph nodes compared to vehicle and untreated controls. We conclude that chronic administration of a peptidomimetic MMP inhibitor via the oral route is feasible and results in inhibition of solid tumor growth, spread and metastasis with increase in survival in this model of human cancer, thus converting aggressive cancer to a more controlled indolent disease. 相似文献
100.
Body surface isochrone mapping was performed in 36 normal subjects and in 85 patients with previous myocardial infarction. Eighty-seven unipolar electrocardiograms distributed over the anterior chest and the back were recorded simultaneously. For each lead, activation time was measured as the time from the onset of QRS to the peak of the R wave. The lead points where R waves were not observed were designated the "no R wave area" (NR area). Isochrone maps of normal subjects had a consistent pattern, with isochrone lines extending from the right upper anterior chest to the left anterior chest and then to the back. NR area was small and was located only on the right upper chest or the upper back. On the isochrone maps of patients with myocardial infarction, abnormal findings were observed; NR area was found in 26 of 28 patients with anterior infarction on the upper to middle anterior chest, in 13 of 22 patients with inferior infarction on the lower chest, and in 24 of 25 patients with anterior and inferior infarction on the upper to lower anterior chest. Activation time was delayed near the NR area (peri-NR area delay) in 37 patients. In patients with apical infarction, an islandlike zone of delayed activation was typically found on the left precordium. These abnormal patterns are considered to indicate local abnormalities in the activation of infarcted myocardium; the NR area indicates dead unexcitable scar, and the peri-NR area delay and islandlike zone of delayed activation indicate partially infarcted myocardium of slow activation. Patients with NR area had greater degree of left ventricular asynergy and lower ejection fraction than those without.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献