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Biomedical subjects

M Shimizu

Publications and source records attributed to M Shimizu.

At least 631 records · Page 35Linked to original sources

Effects of chronic ethanol treatment on inositol 1,4,5-trisphosphate receptors and inositol 1,3,4,5-tetrakisphosphate receptors in rat brain.

In this study, the effects of chronic ethanol treatment on inositol 1,4,5-trisphosphate (IP3) and inositol 1,3,4,5-tetrakisphosphate (IP4) specific binding in rat brain was investigated. In the cerebellum, chronic, but not acute, ethanol treatment caused a decrease in the number IP3 receptors. The effect of chronic ethanol treatment on IP3 and IP3 receptor mRNA levels was also studied in order to determine the mechanisms responsible for the decrease in IP3 receptor binding. Chronic ethanol treatment did not change IP3 levels, indicating that the decrease of IP3 receptors is not caused by the alteration of IP3 levels. Also IP3 receptor mRNA levels had no change after chronic ethanol treatment. These findings suggest that the decrease in IP3 receptors in the cerebellum could be caused by either a decrease in the translation of IP3 receptor mRNA or an increase in proteolysis of IP3 receptors. In contrast, chronic ethanol treatment had no effect on the Bmax or Kd of IP4 specific binding in the cerebellum. It is speculated that a change at the level of the IP3 receptor in the cerebellum may be associated with the development of adaptation and tolerance to chronic ethanol exposure.

Animals↗

Effects of chronic exposure to desipramine and mianserin on Ca2+ mobilization induced by noradrenaline, acetylcholine, and high K+ in rat frontocortical neurons.

We examined the chronic effects of desipramine and mianserin on increases of intracellular Ca2+ concentration ([Ca2+]i) induced by noradrenaline (NA), acetylcholine (ACh), or high K+ in cultured neurons of rat frontal cortex, using fluoromicroscopic analysis with Ca(2+)-sensitive dye fura-2. NA- and ACh-induced [Ca2+]i increases were abolished in the presence of 1 microM prazosin and 1 microM atropine, respectively, and partially inhibited in the absence of extracellular Ca2+. When cultures were treated with 1 microM desipramine for 5 days, the dose-dependent curves of NA- and ACh-induced (0.01-100 microM) [Ca2+]i increases were similar to those of the control cultures. Neither NA- nor ACh-induced [Ca2+]i increases were affected by desipramine exposure, even at a concentration of 10 microM. Treatment with mianserin (0.1, 1, or 10 microM) for 5 days had no effect on either NA- or ACh-induced [Ca2+]i increases. Additionally, [Ca2+]i increases induced by high K+ (12.5-50 mM) were not affected following chronic 10 microM desipramine exposure for 5 days. Thus, chronic antidepressant exposure does not modify the [Ca2+]i increased mediated by alpha 1-adrenoceptors, muscarinic cholinergic receptors, or voltage-sensitive Ca2+ channels. Changes in Ca2+ mobilization may not be one of the mechanisms of antidepressants.

Acetylcholine↗

Doppler assessment of physiological stenosis at the bifurcation of the main pulmonary artery: a cause of functional murmur in neonates.

A systolic heart murmur is not infrequently recognized in healthy newborn infants, especially those with a low birth weight. This study aimed at assessing the hemodynamics at the bifurcation of the main pulmonary artery using Doppler echocardiography and to correlate the results with this murmur. The peak velocities of main pulmonary artery (MPAV) and right pulmonary artery (RPAV) were studied in 25 low-birth-weight infants who had recovered from acute stage and presented with a systolic murmur, and the ratio of RPAV/MPAV was calculated. Another compatible 25 healthy low-birth-weight infants without a murmur were enrolled as the control group. The initial MPAV values were 79.8 +/- 20.7 (range 51-152) cm/s and 80.7 +/- 14.2 (range 60-111) cm/s in the heart murmur group and in the control group, respectively (p > 0.05). The initial RPAV values were 193.4 +/- 60.2 (range 118-388) cm/s and 99.8 +/- 15.5 (range 76-132) cm/s in the heart murmur group and in the control group, respectively (p < 0.0001). The initial RPAV/MPAV ratios were 2.46 +/- 0.61 (1.59-3.92) and 1.25 +/- 0.14 (0.94-1.47) in the heart murmur group and in the control group respectively (p < 0.0001). When the murmur disappeared after a period of 2-5 months, no significant differences in the last RPAV and RPAV/MPAV ratios between both groups could be found. The RPAV in the heart murmur group faded significantly to 118.7 +/- 16.9 cm/s, and so did the RPAV/MPAV ratio to 1.24 +/- 0.12 (p < 0.0001). A transient functional murmur recognized in healthy premature infants at about 1 month of age is caused by the pressure gradient that implies a physiological stenosis at the bifurcation of the main pulmonary artery. The RPAV is higher than the MPAV, and the RPAV/MPAV ratio is usually over 1.5. The RPAV became slower, and the RPAV/MPAV ratio fell as the murmur faded with age.

Arterial Occlusive Diseases↗

Effect of substrate on indirect immunofluorescence test for canine pemphigus foliaceus.

The effect of substrate on indirect immunofluorescence (IIF) tests for the detection of circulating autoantibodies was studied by examining sera from 14 canine pemphigus foliaceus patients, six sera with non-pemphigus dermatoses and ten normal dog sera against five different substrates from three species. These substrates included bovine esophagus, bovine nose, bovine tongue, monkey esophagus, and canine nose skin. Nine out of 14 (64.3%) sera from patients with canine pemphigus foliaceus showed intercellular space staining by indirect immunofluorescence using bovine esophagus as substrate. However, sera from nonpemphigus dermatoses and normal dog did not react with bovine esophagus. In other substrates, only bovine tongue showed 1/8 (12.5%) positive reaction at the intercellular space by sera from canine pemphigus foliaceus. Dog nose skin showed the intercellular space staining against ten of ten (100%) normal dog serum. Monkey esophagus showed the fluorescent deposit at the intercellular space in four of nine (44.4%) of pemphigus foliacues dog sera, however, four of ten (40%) of normal dog sera revealed nonspecificity intercellular staining. These results indicate that the sensitivity and the specifity of IIF test in canine pemphigus foliaceus depend on the substrate. The best substrate for detecting circulating autoantibody in canine pemphigus foliaceus patients among five different substrates was bovine esophagus because of its sensitivity and high specificity. The diagnosis of canine pemphigus foliaceus should be made on the basis of a combination of clinical signs, histopathology, direct immunofluorescence, and the detection of circulating autoantibody.

Animals↗

Primary structure of the porcine 89-kDa enamelin.

The primary structure of the 89-kDa enamelin found in porcine secretory enamel at an early stage of development was investigated. The fragments of the enamelin cDNA were amplified by polymerase chain-reaction from the first-strand enamelin cDNA, and were sequenced. The results indicated that the 89-kDa enamelin consisted of 627 amino acid residues and had a molecular mass of 70,448. A hydrophobic domain is located in the region of the 21st-62nd amino acid residues of the molecule. Acidic domains are located in two regions of the molecule-one in the region of the 135th-238th amino acid residues and the other in the C-terminal region. A basic domain is located in the region of the 239th-360th amino acid residues. The results also indicated that the low-molecular-weight enamelins were fragments derived from a prototype enamelin.

Amino Acid Sequence↗

Possible actions of metalloproteinases found in porcine enamel in an early secretory stage.

In an outermost layer of porcine secretory enamel, metalloproteinases were detected by enzymography with gelatin used as a substrate. When the sample extracted from the outermost layer of the secretory enamel was incubated with calcium ions at 37 degrees C prior to electrophoresis, an increase of the 34-kDa proteinase activity and a decrease of the 76- and/or 78-kDa proteinase activities were observed. The results suggest that the metalloproteinases mediate the conversion from 76- and/or 78-kDa proteinases to the 34-kDa proteinase or the activation of a latent type of the 34-kDa proteinase, and that their activities are regulated by free Ca ions.

Animals↗

[Research and development of zonisamide, a new type of antiepileptic drug].

Zonisamide (1,2-benzisoxazole-3-methanesulfonamide, AD-810) is a broad spectrum antiepileptic drug which has been launched in Japan and South Korea. It lacks the ureide structure included in most of the existing antiepileptic drugs. Zonisamide was synthesized by the sulfonation and the successive amination of 1,2-benzisoxazole-3-acetic acid in a very poor yield. After several efforts to optimize the compound, zonisamide was selected based on the balance of the efficacy and safety. The yield was greatly improved by the development of new synthetic routes. Zonisamide suppressed maximal electroshock seizures in mice, rats, rabbits and dogs. Its therapeutic plasma concentration range between anticonvulsant and neurotoxic effects was much wider than that of the existing antiepileptic drugs. In electroencephalographic studies on animal models of epilepsy, zonisamide, like phenytoin and carbamazepine, restricted the spread or propagation of seizures and, like sodium valproate, it suppressed the epileptogenic focus activity. Zonisamide was effective in several kindling models. In clinical studies, zonisamide exerted the efficacy against partial seizures (simple, complex, secondarily generalized seizures) and some generalized seizures (tonic-clonic, tonic, atypical absence seizures) that were comparable to that of carbamazepine and sodium valproate, respectively. Zonisamide was also effective in monotherapy. The adverse effects related with zonisamide were mainly drowsiness, ataxia, loss of appetite and gastrointestinal symptoms. Serious adverse effects which may be life-threatening have not been reported.

Animals↗

A case of hypertrophic obstructive cardiomyopathy associated with autonomic nervous dysfunction.

Autonomic nervous dysfunction has recently been considered to be an etiological factor in syncope and sudden death in cases of hypertrophic cardiomyopathy. However, the precise mechanism is still unknown. A 73-year-old woman with obstructive hypertrophic cardiomyopathy was hospitalized with complaints of impaired consciousness; faintness 3 to 4 h after meals, lightheadedness while walking, and syncope during and after defecation and micturition. Faintness was induced by alimentary hypoglycemia related to gastrectomy performed 5 years previously. Lightheadedness and syncope were accounted for by autonomic nervous failure combined with an impairment of alpha 1-adrenoceptor in vasoconstriction and the carotid sinus hypersensitivity which accompanied preceding events such as abdominal pain, defecation and micturition, which could enhance the vagally-mediated baroreceptor reflex.

Aged↗

Clinical features of prognosis of Japanese patients with anomalous origin of the coronary artery.

Anomalous origin of the coronary artery can lead to angina pectoris, acute myocardial infarction or even sudden death in the absence of atherosclerosis. However, in Japan, this anomaly is usually treated medically rather than surgically. To clarify the clinical features of anomalous origin of the coronary artery in Japanese and the prognosis of such patients who are treated medically, we reviewed 56 patients with anomalous origin of the coronary arteries. The mean age of these patients was 55.9 +/- 11.5 years. Anomalous origin of the right coronary artery from the left sinus of Valsalva was seen most frequently (78.6%). In contrast, we found no cases of anomalous origin of the left coronary artery from the right sinus of Valsalva traversing between the aorta and the pulmonary trunk. A history of syncope (14.3%) and aorta regurgitation (21.4%) was frequent and serious complications during exercise stress testing occurred in 5 patients. These patients were treated medically, such as by limiting exercise or by the oral administration of medicine. During the follow up period (mean 5.6 +/- 4.2 years), death directly related to anomalous origin of the coronary artery was not found despite the lack of surgical treatment. Our results suggest that the prognosis of these middle-aged-to-elderly patients without atherosclerosis is relatively good, despite the lack of surgical treatment.

Adult↗

Inhibitory effect of arphamenine A on intestinal dipeptide transport.

Arphamenine A, an Arg-Phe analog without a peptide bond, has been reported to be a possible inhibitor of the peptide transporter [H. Daniel and S.A. Adibi, FASEB J., 8, 753 (1994)]. The present study demonstrated that arphamenine A is not a real inhibitor, but is a substrate for the transporter, being transported transepithelially under a proton gradient. The substrate specificity of the peptide transporter was wider than expected.

Biological Transport, Active↗

Mycoplasma hyorhinis infection levels in lungs of piglets with porcine reproductive and respiratory syndrome (PRRS).

The infection levels of Mycoplasma hyorhinis, M. hyopneumoniae and M. hyosynoviae in the lung of piglets were examined in relation to porcine reproductive and respiratory syndrome (PRRS). These animals consisted of 43 PRRS piglets with PRRS, 2 piglets infected with PRRS virus but symptom-free, and 10 control piglets free of PRRS virus and its antibody. M. hyorhinis was isolated from 40 of the 43 PRRS piglets, from 1 of the 2 latent infected piglets and from 3 of the 10 control piglets. The number of M. hyorhinis isolated from the lungs of PRRS piglets was more than 10(5) CFU/g, but those isolated from the latent infected piglets and the control piglets were less than 10(3) CFU/g. In addition to this, Haemophilus parasuis and Pasteurella spp. were frequently isolated from the piglets with PRRS (51.2% and 25.6%, respectively). On the other hand, M. hyopneumoniae was isolated from only 4 of 55 piglets tested, and M. hyosynoviae was not isolated. M. hyorhinis was also detected directly in the lung emulsion samples from almost all the PRRS piglets using a polymerase chain reaction-based method.

Animals↗

Nested PCR for detection and typing of porcine reproductive and respiratory syndrome (PRRS) virus in pigs.

A nested polymerase chain reaction (PCR) was developed to detect porcine reproductive and respiratory syndrome (PRRS) virus. A common primer set for European and North American type isolates of PRRS virus was designed for reverse transcription PCR, and a specific primer set for each of the 2 type isolates was designed for nested PCR. The PCR that used a specific primer set detected the corresponding type of the virus at a level equivalent to 1 TCID50/100 microliters, but not the other type of isolates. Therefore, the method clearly differentiated the 2 types of virus from each other. The detection of PRRS virus by the nested PCR was as sensitive as virus isolation in cultures of porcine alveolar macrophages from infected pigs at the acute stages, and was more sensitive from pigs at the convalescent stages. The infecting virus type was determined by use of 2 specific primer sets even when virus isolation was negative in naturally infected pigs. It was concluded that the nested PCR is useful for diagnosis and typing of PRRS virus and studies of persistent infection by the virus.

Animals↗

Isolation of porcine respiratory coronavirus from pigs affected with porcine reproductive and respiratory syndrome.

Four cytopathogenic viruses were isolated in CPK cells derived from porcine kidneys from tonsils and lungs of 3 of 15 pigs affected with porcine reproductive and respiratory syndrome virus. Physicochemically and morphologically, the isolates were similar to a coronavirus. The isolates were not distinguished from transmissible gastroenteritis virus (TGEV) by a neutralization test using polyclonal antibodies, but differentiated from TGEV by monoclonal antibodies capable of discriminating between TGEV and porcine respiratory coronavirus (PRCV), indicating that the isolates were PRCV. In a serological survey of 30 serum samples each collected from about 50 days old pigs in the 2 affected farms, 29 (97%) and 15 (50%) sera were positive for neutralizing antibody against the isolate with the titers ranging from 2 to 64, respectively.

Animals↗

Electrophoretic study of lactate dehydrogenase and alkaline phosphatase isoenzymes of the Mongolian gerbil (Meriones unguiculatus).

Lactate dehydrogenase and alkaline phosphatase isoenzymes of the Mongolian gerbil were examined using electrophoretic techniques and were compared with those of the mouse, rat, and guinea pig. Five isoenzymes of lactate dehydrogenase (LDH) were detected in the gerbil with LDH2 and LDH5 being equally dominant. Two bands of alkaline phosphatase (ALP) were distinguished in sera treated with neuraminidase in the gerbil and the relative activity of the cathodic fraction was greater than those of the mouse and rat. Genetic polymorphism was not found among the coat color variants of the Mongolian gerbil. A comparative study on LDH and ALP revealed distinct interspecific differences in the rate of the electrophoretic migration of the respective isoenzymes among the mouse, rat, guinea pig, and the Mongolian gerbil.

Alkaline Phosphatase↗

Effect of M-711 on experimental skin reactions induced by chemical mediators in rats.

We investigated the mechanism of anti-allergic action of Moku-boi-to (M-711) and effects on the skin reactions induced by chemical mediators as the model of allergic dermatitis. More than 20 mg/kg BW of M-711 significantly suppressed the enhancement of capillary permeability induced by histamine, LTC4, and anti-serum in the rat skin. Anti-histaminic effect of 40 mg/kg BW of M-711 was equipotent to same as the optimal doses of azelastine and diphenhydramine, respectively. As to anti-LTC4 action, 20 mg of M-711 was compared to the optimal dose of diphenhydramine. Those data showed that M-711 has the suppressive effects on the chemical mediators such as histamine and LTC4 and reduced the skin reaction induced by antigen-antibody response.

Animals↗

Effect of M-711 on experimental asthma in rats.

We experimentally demonstrated the anti-asthmatic effects of M-711, the dry extract of a Chinese herb medicine called Mokuboi-to, using the rat model of allergic asthma. Allergic asthma was induced by the antigen-antibody reaction in the rats and they showed anaphylactic symptoms accompanied with hypotension and depression of respiratory function. More than 20 mg/kg body weight of M-711 was effective in relieving the asthmatic symptoms like methylephedrine. It could lessened the suppress of respiration and provided a good improvement. It also reduced a drop of the blood pressure and improved it quickly. Its ingredients alone were much less effective than M-711 as the total. Those data suggested that M-711 was effective for alleviating allergic asthma in the present study and that its action was provided by interaction of all ingredient raw herbs of M-711.

Animals↗

Production of monoclonal antibodies against classical swine fever virus and their use for antigenic characterization of Japanese isolates.

Twenty monoclonal antibodies (MAbs) were produced against the virulent ALD or vaccinal GPE- strains of classical swine fever (CSF) virus. The MAbs were divided into 7 groups on the basis of the difference in the reaction spectrum to various CSF and bovine viral diarrhea-mucosal disease (BVD-MD) viruses. The panel of the MAbs could classify 20 CSF viruses into 6 types, and could discriminate between not only CSF and BVD-MD viruses but also the vaccinal GPE- strain and the field isolates of CSF virus. The results indicated that the MAbs were useful for diagnosis and investigation of CSF viruses.

Animals↗