Biomedical subjects
Publications and source records attributed to Y Yajima.
Diatom concentrations in seawater were examined monthly at four aquatic areas. Diatom concentrations inside a bay showed a monthly variation, but these were detectable. On the other hand, in the open sea around the continental shelf break, there were few diatoms in any season. When a person drowns in the open sea, the diatom test cannot be expected to function reliably.
The central neural circuit mediating baroreceptor control of sympathetic vasomotor outflow involves an excitatory projection from arterial baroreceptors to nucleus tractus solitarius, an excitatory projection from nucleus tractus solitarius to the caudal ventrolateral medulla, an inhibitory projection from the caudal ventrolateral medulla to the rostral ventrolateral medulla (RVLM), and an excitatory projection from the RVLM to sympathetic preganglionic neurons in the spinal cord. For this circuit to be operational, the relevant neurons in the RVLM must be tonically active. Indeed, numerous studies have demonstrated that RVLM vasomotor neurons are tonically active; however, little is known regarding the nature of the tonic excitatory drive to these neurons. We present a model in which RVLM vasomotor neurons are tonically excited by inputs to the RVLM that can be blocked by the excitatory amino acid receptor antagonist, kynurenic acid, as well as an input from the caudal ventrolateral medulla that is not sensitive to kynurenic acid.
The purpose of this study was to investigate the treatment of 190 cases of ameloblastoma in our department from 1966 to 1994. The statistical results with regard to age, sex and region agreed with those of other investigators. Thirty-five of 43 (81.4%) cases underwent enucleation in 1960s, but the sixteen of 27 (59.3%) cases underwent partial resection of mandible in 1990s. The defect of mandible was reconstructed with iliac bone grafting since 1968, grafts with a mixture of iliac blocked bone and PCBM (particulate cancellous bone and marrow) have been used since 1975. Grafting of the inferior alveolar nerve with the great auricular nerve to the defect has been performed in our department since 1977. Recently, technique involving pull-through of the inferior alveolar nerve bundle has been used in our department. When the reconstruction method for the mandible and nerve has been established, it becomes possible to operate radically and positively. Recurrence occurred in 17 cases after the primary enucleation. It is thought that the primary treatment of ameloblastoma must be as radical as possible. It appears to be necessary to observe progress and perform follow-up in cases of ameloblastoma for more than ten years, because there was one recurrence at 9 years and 4 months after the first operation. In fact, three quarters of our cases were lost to follow-up. Such losses can problems in confirming recurrence and responding rapidly.
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The present study was designed to investigate the effect of a selective GABA(B) receptor agonist baclofen on the pain-like nociceptive behavior (scratching, biting and licking) induced by intrathecal (i.t.) injection of N-methyl-D-aspartate (NMDA) or (+)TAN-67, the enantiomorphs of 2-methyl-4aalpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12aalpha-octahydro-quinolino[2,3,3g]isoquinoline (TAN-67), in the mouse. NMDA (0.05-0.2 microg/mouse) given i.t. immediately caused nociception in a dose-dependent manner. The nociception was significantly antagonized by i.t. co-injection with dizocilipine (0.1-1.0 microg/mouse), a non-competitive NMDA receptor antagonist. I.t. co-injection with baclofen (37.5-150 ng/mouse) significantly reduced the NMDA-induced nociceptive behavior in a dose-dependent fashion. The inhibition produced by baclofen was completely reversed by a selective GABA(B) receptor antagonist 2-hydroxysaclofen (0.15 and 0.3 microg/mouse). An i.t. injection of (+)TAN-67 at doses of 3.75-15 microg/mouse elicited a long-lasting and a dose-related nociception. The nociceptive behavior induced by (+)TAN-67 given i.t. was markedly suppressed by i.t. co-injection with baclofen (3-30 ng/mouse), and the inhibitory effect of baclofen was prevented by i.t. injection of 2-hydroxysaclofen (1 and 3 microg/ mouse). In addition, the (+)TAN-67-induced nociception was also attenuated by i.t. co-injection with dizocilipine (0.1-1.0 microg/mouse). These results suggest that spinal GABA(B) receptors may be implicated in the expression of nociception elicited by i.t. injection of either NMDA or (+)TAN-67 in the mouse.
Partial nerve injury induced by tying a tight ligature around the sciatic nerve induced a marked hyperalgesia, and this persistent painful state lasted for 14 days in mice. Under these conditions, the nerve injury induced a significant increase in protein level of protein kinase Cgamma isoform in plasma membranes in the spinal cord. We report here for the first time that protein level of TrkB receptor located in plasma membranes was clearly up-regulated in the spinal cord obtained from the nerve-injured mice. These findings suggest that the up-regulation of protein kinase Cgamma associated with activated TrkB receptors following partial sciatic nerve ligation may induce sensitization of synaptic transmission and may in turn cause the persistent pain in mice.
Treatment of rat pituitary GH(4)C(1) cell membranes with calpain, a calcium-activated cysteine protease, increased adenylate cyclase activity, and this activity was inhibited by a calpain inhibitor, leupeptin. Calpain treatment potentiated the activity of guanosine 5'-[gamma-thio]triphosphate (GTP[S]), but did not attenuate MnCl(2) action on adenylate cyclase, suggesting that calpain acted at the G-protein level, rather than directly on adenylate cyclase. This calpain stimulation of adenylate cyclase was inhibited by an antibody raised against the C-terminal portion of G(s)alpha, but not by anti-G(i)2alpha or anti-Gbeta antibodies. Furthermore, it was shown that G(s)alpha is more susceptible to calpain-mediated proteolysis than G(i)2alpha or Gbeta. Therefore the stimulatory effect of calpain on adenylate cyclase is due to the cleavage of G(s)alpha in GH(4)C(1) cell membranes. Proteolysis of G(s)alpha by micro-calpain involved sequential cleavages at two sites, resulting in the generation of a 39 kDa fragment first, and then a 20 kDa fragment, from the C-terminus. Treatment of GH(4)C(1) cell membranes with cholera toxin increased the rate of cleavage. Cholera toxin treatment of intact GH(4)C(1) cells induced the translocation of calpain from the cytosol to the membranes, a hallmark of calpain activation. In addition, treatment of intact GH(4)C(1) cells with a calpain-specific inhibitor, benzyloxycarbonyl-Leu-leucinal, blocked the increased cAMP production and the down-regulation of G(s)alpha, which were produced by cholera toxin or pituitary adenylate cyclase-activating polypeptide. These results suggest that calpain sustains adenylate cyclase in an active form through the cleavage of G(s)alpha to an active G(s)alpha fragment. This is a novel calpain-dependent activation mechanism of G(s)alpha and, thus, of adenylate cyclase in rat pituitary cells.
The present study investigated the effects of micro-, delta- and kappa-opioid receptor agonists on seizures produced by blockade of gamma-aminobutyric acid (GABA)-mediated synaptic transmission in the mouse. The selective GABA(A) receptor antagonist bicuculline (1.25-3 mg/kg) given subcutaneously caused dose-dependent clonic-tonic convulsions. These convulsions were potentiated by the prototypic mu-opioid receptor agonist morphine given subcutaneously 20 min prior to a subconvulsive dose of bicuculline. The potentiation by morphine was completely reversed by pretreatment intraventricularly with the selective mu-opioid receptor antagonist beta-funaltrexamine (0.5 microgram/mouse). Pretreatment intraventricularly with the selective delta-opioid receptor agonists 2-methyl-4aalpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12, 12abeta-octahydro-quinolino[2,3,3-g]isoquinoline ((-)TAN-67) or [D-Pen(2,5)]-enkephalin (DPDPE) showed a dose-dependent increase in the incidence of convulsions. Pretreatment with naltrindole (2 mg/kg, s.c.), a selective delta-opioid receptor antagonist, abolished the enhancement of the bicuculline-induced convulsions by DPDPE. In contrast, pretreatment with the selective kappa-opioid receptor agonist U-50,488H (0.6-80 mg/kg, subcutaneously or 25-100 microgram/mouse, intraventricularly) produced a dose-dependent suppression of the bicuculline-induced convulsions. The inhibitory effect of U-50,488H was completely blocked by pretreatment subcutaneously with nor-binaltorphimine (5 mg/kg), a selective kappa-opioid receptor antagonist. This study demonstrates that activation of both mu- and delta-opioid receptors increases the incidence of convulsions produced by blockade of GABA-mediated synaptic transmission, while stimulation of kappa-opioid receptors has an anticonvulsive effect.
In order to study the pharmacological action of the NO donor SIN-1 upon laryngeal motoneurons, we focally iontophoresed SIN-1 onto single motoneurons identified by antidromic stimulation of the recurrent nerve. SIN-1 produced opposing effects on motoneuron activities. Of 34 identified motoneurons, 38.2% showed a statistically significant decrease (decreasing group), while 29.4% showed an increase in their antidromic response to SIN-1 application (increasing group), respectively. The remaining neurons did not show any change (no change group). When the antidromic spike amplitude during the precontrol period was compared between the three groups, both the increasing and decreasing groups exhibited larger antidromic spikes than those measured in the no change group. The results are discussed in terms of dual pharmacological actions of NO.
PURPOSE: To assess the short-term effects of sildenafil citrate on intraocular pressure in healthy male volunteers and participants in clinical trials. METHODS: Intraocular pressure and pupil diameter were measured in two placebo-controlled studies. Oral doses of sildenafil citrate (VIAGRA; Pfizer Inc, New York, New York) ranged from 10 mg to 150 mg. RESULTS: No major changes in intraocular pressure or pupillometry were detected at any time (1.0-24 hours) after administration of sildenafil. Additionally, of 36 subjects with a medical history of increased intraocular pressure in the sildenafil safety database, none were reported to have a clinically significant increase of their intraocular pressure. During clinical trials, two glaucoma cases were listed as serious adverse events, but were not considered treatment related. CONCLUSION: No clinical abnormalities were observed in intraocular pressure or pupil diameter in subjects receiving sildenafil. Currently, no evidence suggests that long-term treatment with sildenafil has an effect on intraocular pressure or is associated with the development or worsening of glaucoma.
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The anesthetic and cardiovascular effects of a combination of continuous intravenous infusion using a mixture of 100 g/L guaifenesin-4 g/L ketamine-5 mg/L medetomidine (0.25 ml/kg/hr) and oxygen-sevoflurane (OS) anesthesia (GKM-OS anesthesia) in horses were evaluated. The right carotid artery of each of 12 horses was raised surgically into a subcutaneous position under GKM-OS anesthesia (n=6) or OS anesthesia (n=6). The end-tidal concentration of sevoflurane (EtSEV) required to maintain surgical anesthesia was around 1.5% in GKM-OS and 3.0% in OS anesthesia. Mean arterial blood pressure (MABP) was maintained at around 80 mmHg under GKM-OS anesthesia, while infusion of dobutamine (0.39+/-0.10 microg/kg/min) was necessary to maintain MABP at 60 mmHg under OS anesthesia. The horses were able to stand at 36+/-26 min after cessation of GKM-OS anesthesia and at 48+/-19 minutes after OS anesthesia. The cardiovascular effects were evaluated in 12 horses anesthetized with GKM-OS anesthesia using 1.5% of EtSEV (n=6) or OS anesthesia using 3.0% of EtSEV (n=6). During GKM-OS anesthesia, cardiac output and peripheral vascular resistance was maintained at about 70% of the baseline value before anesthesia, and MABP was maintained over 70 mmHg. During OS anesthesia, infusion of dobutamine (0.59+/-0.24 microg/kg/min) was necessary to maintain MABP at 70 mmHg. Infusion of dobutamine enabled to maintaine cardiac output at about 80% of the baseline value; however, it induced the development of severe tachycardia in a horse anesthetized with sevoflurane. GKM-OS anesthesia may be useful for prolonged equine surgery because of its minimal cardiovascular effect and good recovery.
The World Health Organization (WHO) developed practical guidelines for pain relief in cancer patients in 1986. Although morphine is a standard opioid analgesic with sufficient analgesic potency, it also has undesirable effects such as drug dependence. Considering the significant of the management of patients with chronic cancer pain, it is no exaggeration to say that the investigation of morphine dependence is now most required research for pain relief. Various studies provide arguments to support substantial roles for mu-opioid receptors associated with the mesolimbic dopaminergic pathway and the possible involvement of delta-opioid receptors in the rewarding effect by morphine in animals. By contrast, the activation of kappa-opioid receptors leads to the suppression of this effect of morphine. It is noteworthy that chronic inflammatory nociception enhances endogenous kappa-opioidergic system, leading to the suppression of rewarding effects of morphine. These results obtained from the basic research strongly reflect the clinical results that psychological dependence on morphine is not a major concern when morphine is used to control pain for cancer patients. Another limiting factor in the clinical utilization of opioids is that repeated administration leads to the development of tolerance to opioids. At the cellular level, phosphorylation of opioid receptors by protein kinases, especially G-protein-coupled receptor kinase (GRK) and protein kinase C (PKC), is likely to play a major role in these tolerant and dependent states. We recently found that repeated administration of mu-agonist causes a down regulation of mu-receptor-mediated G-protein activation, which is associated with a specific upregulation of PKC gamma isoform. We therefore propose that PKC gamma may play a critical role in the development of morphine tolerance.
The laryngeal motoneurons innervating the cricothyroid muscle (CT) are located in the semicompact formation just ventral to the rostral part of the compact formation of the nucleus ambiguus. The motoneurons innervating the posterior cricoarytenoid muscle (PCA) are located in the loose formation. We retrogradely labeled the CT and the PCA motoneurons using cholera toxin subunit B-conjugated horseradish peroxidase, and determined the ultrastructure and synaptic organization of these neurons. The CT and the PCA motoneurons had the appearance of alpha-motoneurons, i.e., large, oval or polygonal cells containing well-developed organelles and a prominent spherical nucleus. Two kinds of neurons were recognized among the PCA motoneurons. The one (PCA-A) was significantly smaller than the other (PCA-B). The average number of axosomatic terminals in a section was significantly largest in the PCA-B (56.6), smaller in the PCA-A (36.0), and smallest in the CT (32.3) neurons. Most of the axosomatic terminals (64.7%) contained pleomorphic vesicles and made symmetric synaptic contacts (Gray's type II) with the PCA-A neurons, while more than 60% contained round vesicles with asymmetric synaptic contacts (Gray's type I) in the CT (69.5%) and the PCA-B (60.6%) neurons. A few terminals associated with subsurface cisterns were present on all laryngeal motoneurons. These results indicated that the CT motoneurons may receive mostly excitatory terminals, whereas the PCA muscle may be regulated by neurons having many inhibitory terminals, and neurons having many excitatory terminals.
It has been reported that excessive intake of sugar-containing soft drinks results in diabetic ketoacidosis (DKA) or ketosis (DK) in obese patients with non-insulin dependent diabetes mellitus (NIDDM). We describe the clinical characteristics and results of long-term follow-up for 24 newly-diagnosed patients with acute-onset NIDDM presenting with DKA or DK. A history of excessive intake of sugar-containing soft drinks was found in 19 (Group A); serious non-diabetic illnesses were found in 5 (Group B). The range of patient ages in Group A was 16 to 57 years while all patients in Group B were 60 years or older. In Group A, no patient was positive for autoantibodies, specific HLAs for Japanese insulin dependent diabetes mellitus, or mutation of the beta-3-adrenergic receptor gene. The body mass indices (BMIs) at onset and admission and serum C-peptide immunoreactivities at admission and discharge were significantly higher in patients in Group A than in patients Group B. In conclusion, we reconfirmed that excessive intake of sugar-containing soft drinks is one of the contributing factors in DKA or DK-onset NIDDM patients. We found no autoimmune mechanism involved in the pathogenesis and that a polymorphism in the beta-3-adrenergic receptor gene could be associated with the development of soft-drink ketosis.
A group of respiratory neurons in the rostral nucleus ambiguus complex is known to generate the inspiratory and expiratory drives which enable spontaneous respiration to be sustained. Since previous studies indicated that mutual synaptic inhibition is required to produce oscillations between inspiratory and expiratory neurons, it may implicate GABAergic synaptic transmission between each group of neurons. In this study we tried to determine whether most ambiguous respiratory neurons are influenced by GABA(A) receptor-mediated inhibition. Eighty-eight respiratory interneurons showing rhythmic activity in synchrony with the spontaneous respiration were recorded in urethane-chloralose anesthetized Wistar rats. Multibarrel iontophoretic application of GABA(A) antagonist bicuculline produced a remarkable facilitation in maximum burst discharge rate, whereas the agonist muscimol reversed this effect completely. Simultaneous application of GABA and bicuculline increased the discharge rate more than in any single application or in the simultaneous application of GABA and muscimol. These results were statistically significant. These findings suggest strongly that GABA(A) receptors in the ambiguous respiratory neurons may have an inhibitory role in the synaptic transmission for maintaining the respiratory oscillation in the nucleus ambiguus.