Platelet aggregation inhibited by sevoflurane, or by ethanol?
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to T Mizobe.
Explore the source record for details and available documents.
Molecular biological studies have established classification of adrenergic receptors 40 years after Prof Ahlquist first classified them into alpha and beta. They are now classified into 9 subtypes consisting of 400 to 480 amino acids. They belong to a super-family of G-protein coupled receptors. Based on the amino acid sequence, the topography of adrenoceptors is depicted as a snake model twisting itself back and forth through the membrane 7 times.
Recombinant DNA experiments using chimeric receptors containing portions of alpha 2 and beta 2 adrenoceptors demonstrated structure-function relationships of adrenoceptors. The seventh transmembrane domain determines the subtype ligand binding specificity between alpha 2 and beta 2 adrenoceptors. A further investigation by mutagenesis suggests that a direct interaction between subtype specific ligands and specific amino acids such as Phe (412) and Asn (312) in the seventh transmembrane domain of the alpha 2 and beta 2 adrenoceptors respectively. The third cytoplasmic loop is responsible for determining the specificity of interactions between the receptor and G protein. Recombinant DNA technology also demonstrated that seven transmembrane domains of adrenoceptors have a counterclockwise arrangement when viewed from the outside of the cell.
Alpha 2 adrenergic agonists will soon be used in the anesthetic management for their sedative/hypnotic, anesthetic-sparing, analgesic and sympatholytic properties. But the clinically available alpha 2 agonists have unwanted side-effects such as acute hypertension and bradycardia following a bolus injection because these agonists do not discriminate between the 3 alpha 2 adrenoceptor subtypes. Molecular biological methods can identify mediating receptor subtype for each response. Knockout mice study reveals that the alpha 2 B adrenoceptor subtype mediates the hypertensive response to alpha 2 agonists. Knockdown study using the antisense technology demonstrates that the alpha 2 A adrenoceptor subtype mediates the hypnotic and analgesic effects of alpha 2 agonists. The next generation of alpha 2 agonists should be alpha 2 A selective to maximize anesthetic and analgesic effects while minimizing hypertensive response.
Alpha 2 adrenergic agonists currently are used in the anesthetic management of the surgical patient for their sedative/hypnotic, anesthetic-sparing, analgesic, and sympatholytic properties. Experimental and clinical studies have progressed to the point where anesthesiologists are now focusing on the use of these agents for their analgesic and anesthetic effects. This interest has coincided with the development and clinical introduction of dexmedetomidine. Clinical studies using existing alpha 2 agonists have revealed a tremendous potential for these agents that will be fully realized when more selective and specific compounds become available.
Alpha2 adrenergic agonists are used in the anesthetic management of the surgical patient for their sedative/hypnotic properties although the alpha2 adrenoceptor subtype responsible for these anesthetic effects is not known. Using a gene-targeting strategy, it is possible to specifically reduce the expression of the individual adrenoceptors expressed in the central nervous system and to thereby determine their role in hypnotic action. Stably transfected cell lines (PC 124D for rat alpha2A; NIH3T3 for rat alpha2C adrenoceptors) were exposed to 5 microM antisense oligodeoxynucleotides (ODNs) for alpha2A and alpha2C adrenergic receptor subtypes for 3 d. Individual receptor subtype expression, as determined by radiolabeled ligand binding, was selectively decreased only by the appropriate antisense ODNs and not by the "scrambled" ODNs. These antisense ODNs were then administered three times, on alternate days, into the locus coeruleus of chronically cannulated rats and their hypnotic response to dexmedetomidine (an alpha2 agonist) was determined. Only the alpha2A antisense ODNs significantly change the hypnotic response causing both an increase in latency to, and a decrease in duration of, the loss of righting reflex following dexmedetomidine; hypnotic response had normalized 8 d after stopping the ODNs. Therefore, the alpha2A adrenoceptor subtype is responsible for the hypnotic response to dexmedetomidine in the locus coeruleus of the rat.
G protein-coupled receptors (GPCRs) have seven hydrophobic domains, which are thought to span the lipid bilayer as alpha helical transmembrane domains (TMDs). The tertiary structure of GPCRs has not been determined; however, molecular models of GPCRs have generally been based on bacteriorhodopsin, which is functionally unrelated to GPCRs but has a similar secondary structure. We sought to examine the validity of using bacteriorhodopsin as a scaffold for GPCR model building by experimentally determining the orientation of the TMDs of adrenergic receptors in the plasma membrane. In separate experiments, three sequential amino acid residues (Leu-310, Leu-311, Asn-312) in TMD VII of the beta 2 adrenoreceptors were mutated to the amino acids found in the homologous domain of the alpha 2 adrenoceptor (Phe, Phe, Phe). Exchange of Asn-312 and Leu-311 in the beta 2 adrenoceptor resulted in nonfunctional proteins, most likely due to incompatibility of the introduced bulky phenylalanine side chain with adjacent structural domains in the beta 2 adrenoreceptor. This structural incompatibility was "repaired" by replacing the specific beta 2 TMD sequence with an alpha 2 receptor sequence. TMD I and TMD II complemented the Asn-312-->Phe mutation, and TMD III and TMD VI complemented the Leu-311-->Phe mutation. These results indicate that TMDs I, II, III, and VI surround TMD VII in a counter-clockwise orientation analogous to the orientation of TMDs in bacteriorhodopsin.
We present two cases of automatic hyperreflexia (AH) during labour in women with spinal cord damage, in whom AH developed before and after delivery. The AH was successfully controlled using epidural anaesthesia in Case #1, but failed in Case #2. The blood pressure was controlled with nicardipine. However, overdose of nicardipine produces vasodilation and its side effects include headache, flushing and palpitation similar to AH. Considering these effects, we recommend epidural anaesthesia to control AH, because epidural anaesthesia does not only reduce BP, but also blocks the noxious stimuli and relieves the symptoms of AH. Our experience suggests that the epidural catheter can be placed two to three weeks before the date of predicted childbirth, because the onset of labour in a patient with spinal cord damage is difficult to predict and can proceed very rapidly. Also, the epidural catheter is available after the delivery. We recommended the epidural catheter is maintained for 24-48 hr postpartum.
Explore the source record for details and available documents.
Summer-type hypersensitivity pneumonitis (SHP) is a unique type of hypersensitivity pneumonitis and the most prevalent in Japan. Our previous study clarified that the causative agent of the disease is Trichosporon cutaneum, and that the patients with SHP have high titres of antibodies against the serotype-specific antigen of polysaccharide nature which exist in the high molecular weight fraction of the culture supernatant of the yeast. In this study, we purified the serotype-specific antigen of serotype II T. cutaneum by gel filtration and affinity chromatography using a monoclonal antibody, D-8, specific for a high molecular weight antigen of serotype II T. cutaneum, and elucidated the structure of the antigen. This affinity-purified antigen was shown to be an essentially acidic polysaccharide comprising mannose, xylose, and glucuronic acid (6:44:4.7). Chemical analysis showed that this polysaccharide antigen contains a (1-3)-linked mannan backbone attached with short side chains of (1-4)-linked mannose and a small proportion of (1-2)-linked xylose residues by substituting the 2- or 4-positions of the (1-3)-linked mannose residues of the main chain. Approximately one-fifth of the side chains were terminated with glucuronic acid residues. The antigenic epitope of the serotype-specific antigen was shown to involve the terminal glucoronic acid residues as revealed by immunodiffusion test and sandwich enzyme-linked immunosorbent assay using monoclonal antibody D-8.
Summer-type hypersensitivity pneumonitis is the most prevalent type of hypersensitivity pneumonitis in Japan. We constructed a sandwich enzyme-linked immunosorbent assay system for diagnosis of summer-type hypersensitivity pneumonitis in which monoclonal antibodies were used to bind serotype-related polysaccharides to plastic plates, and this system was proven to have sufficient sensitivity and specificity.
We have studied the effects of prostaglandin E1 (PGE1) on the release of lysosomal enzymes such as beta-glucuronidase in leukocyte (beta-GL) and granulocyte elastase (GEL) in 52 patients for major abdominal surgery. All patients were divided into two groups; the PG group (24 patients) and the control group (28 patients). The patients of the PG group received PGE1 continuously at the rate of 0.03 to 0.1 micrograms.kg-1.min-1 during surgery. Plasma levels of GEL and beta-GL, which are known to be the indicators of tissue destruction, were measured during and after surgery. The GEL/granulocyte ratio in the PG group was significantly smaller than that of the control group during surgery. The rate of change of beta-GL was significantly depressed in the PG group compared to that of the control group. These findings suggest that the administration of PGE1 during major abdominal surgery inhibits the release of lysosomal enzymes, and this prevents tissue injury during and after surgery.
We evaluated the usefulness of eptazocine hydrobromide as an adjuvant in patients receiving antipsychotics for long periods. Patients anesthetized with enflurane alone (enflurane group, n = 11), were compared with those anesthetized with enflurane and eptazocine hydrobromide 1 mg.kg(-1) (eptazocine group, n = 10). The mean daily dose of the antipsychotics, converted into the amount of chlorpromazine, was 345 mg in the eptazocine group and 366 mg in the enflurane group. The duration of antipsychotic medication was 14 years in the eptazocine group and 17 years in the enflurane group. The maintenance concentration of enflurane was 0.37% in the eptazocine group and 0.67% in the enflurane group, being significantly lower in the former group. The interval between the termination of operation and removal of the endotracheal tube was slightly shorter in the eptazocine group. The discriminant function of circulatory stability obtained from the measurement of systolic blood pressure and heart rate during anesthesia in the eptazocine group was 481, being significantly lower than 539 in the enflurane group. Both absolute and relative instabilities of systolic blood pressure and heart rate were slightly smaller in the eptazocine group. No side effects associated with eptazocine hydrobromide administration were observed. These results suggest the safety and usefulness of this analgesic in the anesthetic management of patients receiving long-term antipsychotic medication.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
To evaluate the methods and criteria of judgement for the bronchial antigen inhalation challenge test, the test was performed with culture filtrate antigen of serotype I and II of Trichosporon cutaneum in 18 patients with summer-type hypersensitivity pneumonitis from 15 families. The quantity of 15 mg of culture filtrate antigen was adequate, and had no side effects. In the tests, 17 of 18 patients showed a positive reaction to both or either, serotype of antigen. In 36 performances of inhalation, there were 21 positive reactions and 15 negative reactions. According to the criteria of judgment for inhalation challenge test, the positive response rates of observation items were 75% for symptoms and signs, and 51% for laboratory data. Items with a high positive rate were cough, crepitant rales, and decrease of PaO2. On the other hand, low positive rates were observed for decrease of DLco, VC and positive CRP. Items with both high sensitivity and high specificity were cough, crepitant rales and decrease of PaO2. The low positive rate of decreased DLco was due to insufficient improvement before inhalation challenge. It was concluded that our methods and criteria of judgment for bronchial inhalation challenge test are useful.
In recent years, the number of elderly patients who require operation has been increasing. We experienced three patients with perioperative brain infarction, occurring respectively, during the preoperative period, just after operation, and three days after operation. All three patients had more than one of the common risk factors for cerebrovascular accidents, including hypertension, advanced age, hyperfibrinogenemia, diabetes mellitus, and past history of cerebrovascular accident. On the basis of our experience with these three patients, we suggest the following: (1) Waiting period of elective surgery should be reconsidered in some cases with a past history of stroke. (2) Some high-risk patients may benefit from anticoagulative or antiaggregative drugs (e.g. low-molecular dextran or prostaglandin E1) to prevent brain ischemia. (3) Abrupt control of hypertension or diabetes mellitus status undoubtedly adversely affects the patient's general condition; and (4) A practical monitoring system to detect regional brain ischemia during operation under general anesthesia should be developed.
We experienced troubles caused by mounting an anesthesia machine and a pump oxygenator on an oxygen pressure-resistant hose that connected the central piping system with the anesthesia machine. Therefore, we measured the resistance of 9 types of hose assemblies to collapsing loads by the method in the International Standardization Organization (ISO) 5359. Two types of hose made in the U.S. were highly resistant. On the other hand, 7 types of domestic hose tended to be obstructed with collapsing loads, and 3 of them did not fulfill ISO's criteria. To prevent anesthetic accidents, improvements in the property of hose assemblies and the establishment of their industrial standardization are urgently needed.