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Biomedical subjects

M Miyamoto

Publications and source records attributed to M Miyamoto.

At least 343 records · Page 19Linked to original sources

Survival-promoting effect of NGF on in vitro septohippocampal neurons with cholinergic and GABAergic phenotypes.

Recently, we demonstrated a survival-promoting effect of nerve growth factor (NGF) on cultured hippocampus-projecting neurons from developing septum/diagonal band region using fluorescent latex microspheres as a retrograde neuronal marker (Arimatsu et al., 1989). In the present study, we characterized these projection neurons by combining the retrograde cell labeling and histochemical stainings for acetylcholinesterase (AChE) activity and NGF receptor-, choline acetyltransferase- (ChAT-) and gamma-aminobutyric acid- (GABA-) immunoreactivities. The surviving microsphere-labeled neurons were, for the most part, immunoreactive for NGF receptor in the culture. A great majority (about 90%) of the microsphere-labeled neurons showed strong AChE activity and ChAT-immunoreactivity. The number of strongly AChE-positive neurons and that of ChAT-immunoreactive neurons in the culture supplemented with NGF was much greater with than without exogenous NGF. In addition, a major part (about 70%) of the microsphere-labeled neurons exhibited GABA-immunoreactivity in the presence of NGF. The number was also much greater than that without NGF. A considerable portion of cultured septal cholinergic neurons were shown to express GABA-immunoreactivity by a two-color immunofluorescence labeling experiment for ChAT and GABA. These findings are consistent with the assumption that NGF plays an important role in the development and organization of the cholinergic and GABAergic septohippocampal systems by supporting the neuronal survival, and raise a possibility that cholinergic and GABAergic fractions of the septohippocampal neurons may be developmentally correlated.

Acetylcholinesterase↗

Relationship between brain damage and memory impairment in rats exposed to transient forebrain ischemia.

The relationship between changes in learning behavior and neurological damage following transient forebrain ischemia was studied in rats. The transient forebrain ischemia was induced by 4-vessel occlusion, and behavioral experiments were started 4 weeks later when histological damage to the brain seemed to have stabilized. Histological evaluation of brain damage was conducted after completion of the behavioral studies. The rats showed marked learning impairment in a radial maze task done from 4 to 10 weeks after ischemia. In particular, there was an increase in the number of working memory errors according to the duration of forebrain ischemia. However, the same rats showed good avoidance responses in a passive avoidance task done 12 weeks after ischemia. The rats also showed good acquisition of escape response in a water maze task carried out 13 weeks after ischemia, but showed slight impairment of spatial navigation in the transfer test. Marked neuronal degeneration was observed in the hippocampal pyramidal cells of the rats exposed to ischemia. This neuronal damage was closely related to memory impairment in the radial maze task, as demonstrated by a significant negative correlation (r = -0.609 or -0.709) between the number of surviving neurons and the number of reference or working memory errors. These results suggest that rats exposed to transient forebrain ischemia show marked impairment of both reference and working memories as a result of postischemic hippocampal damage.

Animals↗

Effect of synthetic prostaglandin E1 analog (ornoprostil) on gastric emptying and pancreatic polypeptide release after solid-meal ingestion in man.

The effect of orally administered ornoprostil, 17S,20-dimethyl-6-oxoprostaglandin E1 methyl ester, on gastric emptying and on pancreatic polypeptide (PP) release after solid meal ingestion, was investigated in man. A radionuclide technique was used to measure gastric emptying of eight healthy volunteers. In addition, four parameters [SI (starting index): the lag time in the start of emptying; K value: the emptying rate; T1/2: the half emptying time; 120 min RR: the percent retention at 120 min] were determined for evaluation. Also, the PP response was analyzed according to two parameters: IPPRSI the integrated PP response for periods up to SI, and IPPR120, the integrated PP response for 120 min. The results demonstrated that 5 micrograms of orally administered ornoprostil significantly reduced the gastric emptying rate of solid meal (T1/2 and 120 min RR, P less than 0.05). However, ornoprostil affected neither the basal PP concentrations nor the cephalic phase of PP secretion which was determined as IPPRSI. This thus suggests that ornoprostil affects the gastric motor function without interfering with the vagal-cholinergic pathway to the stomach.

Adult↗

Evaluation of a new calcium containing cardioplegic solution in the isolated rabbit heart in comparison to a calcium-free, low sodium solution.

Isolated perfused rabbit hearts were studied to compare the effects of 3 hour ischemic arrest following either calcium-free or calcium-containing cardioplegia, on the recovery of isovolumic function of the left ventricle, coronary flow, release of creatine phosphokinase and myocardial water content. The hearts perfused with the calcium-containing solution (Ca 0.5 mmol/L) showed better recovery of the developed pressure in the left ventricle, and its first derivative and compliance. Coronary flow at a constant perfusion pressure was better restored during reperfusion in the hearts with calcium-containing solution. The release of less CPK and a lower water content were also observed in the hearts reperfused with calcium-containing solution. We concluded that calcium-containing cardioplegic solution with a high concentration of magnesium (10 mmol/L) was superior to calcium-free solution for myocardial protection.

Animals↗

The effects of R-75,317 on antiglomerular basement membrane glomerulonephritis in rats.

Platelet-activating factor (PAF) is a potent inflammatory mediator which is released by various inflammatory cells and produced by certain tissues, including the kidney. PAF has been shown to increase glomerular permeability to protein and to decrease glomerular filtration rate (GFR) by contracting mesangium. On the basis of these observations, it has been suspected that PAF may play a role as mediator of glomerular damage in glomerular nephritis. To examine this possibility, we studied the effects of a specific PAF antagonist, R-75,317, on the development of an experimental model of anti-glomerular basement membrane (anti-GBM) glomerulonephritis. Glomerulonephritis was initiated by injecting rabbit anti-rat GBM serum into rats. Proteinuria gradually developed after serum injection, plateaued at week 2, and remained at the high level of week 2 throughout the experimental period (6 wk). Chronic treatment with R-75,317 (10 mg/kg/day i.p.) tended to delay the onset of proteinuria and significantly accelerated the recovery phase. Creatinine clearance (Ccr) fell to 40% at week 3. R-75,317 treatment completely prevented this decline of Ccr. Histological changes in this model (glomerular hypertrophy, proliferation of mesangial matrix and interstitial fibrosis) were also ameliorated by the R-75,317 treatment. The results suggest that PAF may play a role in the development of glomerulonephritis and that PAF antagonists could be used in the treatment of human renal disease.

Acetylglucosaminidase↗

Interleukin-6 improves the survival of mesencephalic catecholaminergic and septal cholinergic neurons from postnatal, two-week-old rats in cultures.

Interleukin-6 (human recombinant) supported the survival of cultured mesencephalic, catecholaminergic and septal cholinergic neurons from postnatal, two-week-old (P13-P15) rats. Significantly, more catecholaminergic neurons, stained by monoclonal anti-tyrosine hydroxylase antibody, were found in cultures supplemented with interleukin-6 at a concentration of 5 ng/ml than in cultures not treated with interleukin-6. The optimal dose used was 50 ng/ml. The survival effect of interleukin-6 on postnatal rat, tyrosine hydroxylase-positive neurons was observed both in cultures using serum-containing and serum-free medium. Contents of dopamine and noradrenaline in cultures with interleukin-6 were also larger than in control cultures. Interleukin-6 also increased the survival of cultured embryonic (E17) rat midbrain tyrosine hydroxylase-positive neurons. The effect on these neurons was, however, smaller, and the optimal dose of interleukin-6 was nearly 5 ng/ml. Interleukin-6 also supported the survival of cultured postnatal (P13) rat septal cholinergic neurons, visualized by acetylcholinesterase staining. The concomitant addition of mouse nerve growth factor (100 ng/ml) and interleukin-6 (50 ng/ml) had a synergetic effect on the survival of acetylcholinesterase-positive neurons in culture. Our data suggest that the survival of cultured tyrosine hydroxylase-positive, mesencephalic, and acetylcholinesterase-positive, septal neurons from postnatal two-week-old rats was supported by interleukin-6, just as there was a different dose dependency of interleukin-6 on the cultured postnatal neurons compared with embryonic neurons.

Animals↗

A case of recurrent extraforaminal lateral lumbar disc herniation occurring at the same level and on the opposite side.

We reported the only known case of recurrent extraforaminal lumbar disc herniation occurring at the same level but on the opposite side. In performing lumbar disc puncture for discography, when an extraforaminal bulge is seen on CT scan, we recommend puncture through the side opposite the bulge to prevent new herniation even if the symptoms are located on the side of the puncture.

Humans↗

Effects of thoracic epidural anesthesia on myocardial pH and metabolism during ischemia.

The effect of thoracic epidural anesthesia (TEA) on the ischemic myocardium was examined in open-chest dogs anesthetized intravenously. Ischemia induced by brief coronary artery occlusion caused an elevation of the ST segment in epicardial ECG and a reduction in myocardial pH and contractile force. TEA with 0.15 ml/kg of 0.4% bupivacaine solution attenuated an ischemia-induced decrease in myocardial pH and an increase of the ST segment in epicardial ECG. This attenuation was maintained even after the restoration of blood pressure and heart rate, which had been decreased significantly after TEA, to pre-TEA levels, suggesting that a beneficial effect of TEA should not be confined to its hemodynamic changes such as decreased blood pressure and heart rate. In contrast, the subendocardial contents of ATP, creatine phosphate (CP) and lactate were not affected by TEA, either in the presence or the absence of 5 min LAD occlusion. These results suggest that neither hemodynamic nor metabolic changes are responsible for the reduced myocardial ischemic acidosis induced by TEA after brief coronary artery occlusion. The acidosis-saving property of TEA is favorable for the ischemic heart.

Adenosine Triphosphate↗

Alloimmune neonatal neutropenia in monozygous twins. High-dose intravenous gammaglobulin therapy.

An indirect immunofluorescence test using a flow cytometer (FACS420) was useful for detection of antineutrophil antibodies (anti-NA2 antibodies) in a case of monozygous twins with alloimmune neonatal neutropenia. When high-dose intravenous gammaglobulin (300 mg/kg for five consecutive days) was given to one twin, the increase in neutrophils was not obvious. Although neutropenia persisted for about three months, no infections were observed in either of the twins.

Autoimmune Diseases↗

Molecular cloning and sequence analysis of antigen gene tdpA of Treponema denticola.

We isolated and characterized an immunogenic protein of an oral spirochete, Treponema denticola Johnson. A genomic DNA library constructed with bacteriophage lambda EMBL3 as a vector was immunologically screened with a rabbit antiserum against the whole cells. Using Western immunoblot analysis, we found a particular clone encoding an antigen with a molecular weight of 53,000; we designated the antigen as T. denticola protein A (TdpA). Complete sequence determination revealed an open reading frame of 1,419 bp and a signal peptide sequence that was homologous to that of bacterial lipoprotein. Southern hybridization analysis revealed that the tdpA gene is highly conserved in six tested strains of T. denticola species. Furthermore, we found that sera from some periodontitis patients contained antibody against the TdpA protein, although the reactivities of the antibodies varied among individuals.

Amino Acid Sequence↗

Structure-activity studies on triazolothienodiazepine derivatives as platelet-activating factor antagonists.

A series of triazolodiazepines was synthesized and evaluated for anti-platelet activating factor (PAF) activities. Structure-activity relationship (SAR) studies on this series revealed that the introduction of a methyl group into the 8-position of the thienodiazepine nucleus can lead to a lengthening of the duration of action. Introduction of a methyl group produced an asymmetric center and the enantiomers so formed were separated with an optical resolving column. In the in vitro assay system, the (+)-isomers displayed 50-200 times more potent anti-PAF activity than the (-)-isomers. After comparison of toxicology and pharmacokinetics, (+)-6-(2-chlorophenyl)-3- cyclopropanecarbonyl-8,11-dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4' ,3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine (35(+)-isomer, E6123) was selected from among the compounds synthesized as a candidate for clinical study.

Animals↗

Effect of estrogen replacement on liver function in ovariectomized rats.

The effect of estrogen (17 beta-estradiol; E2) replacement on the liver function was examined in ovariectomized rats. Ovariectomy decreased serum transaminase activity and physiological dosage levels of E2 replacement returned the activity up to or above non-ovariectomized levels. Under the conditions of this experiment the elevated serum transaminase levels in the E2 replacement were not coincident with histological changes suggestive of liver dysfunction. The elevations of both serum glutamic oxaloacetic transaminase (GOT) and serum mitochondrial GOT were accompanied by increased hepatic tissue activity, suggesting that the elevated serum levels can be attributed to the accelerated synthesis of the enzymes. On the other hand, the elevation of serum glutamic pyruvic transaminase was not accompanied by increased tissue activity in the original organs, namely liver, kidney, heart and skeletal muscle. Ovariectomy decreased serum albumin and inhibited development of rough endoplasmic reticulum in the liver, and E2 replacement returned them up to or above the non-ovariectomized levels.

Alanine Transaminase↗

Adenocarcinoma in the ascending colon of ACI strain rat foster bred by WF-Osaka female rat.

We now keep HFRSV free WF-Osaka rats and ACI rats together in the separate three animal rooms (animal room 1, 2 and 3) and the incidence of colon carcinoma is still high on the WF-Osaka rats in animal room 1 with the high humidity. Two female ACI rats developed colon carcinomas in the ascending colon. The gross and the histological appearance of the colon carcinoma were completely the same as those of WF-Osaka rats. ACI and WF-Osaka rat strain together have been kept bred in neighborhood of each other in different racks in the identical animal room 1. To obtain HFRSV free ACI rat strain, Antecedents born by cesarean section of ACI female pregnant rat were foster-bred by WF-Osaka female nursing rat incidentally, and at the fourth mating generation after the start of foster-breeding, they developed colon carcinomas at the age of four months. Before five out of eight F1 hybrids by WF-Osaka cancer carrying female rat x male ACI rat had developed the same colon carcinoma, but none of F1 hybrids by the contrary mating had developed colon carcinomas in this same animal room 1. Animal room 1 and 2 where there was a high incidence of colon carcinomas, had happened to be kept moistened. However, after disinfection of these animal rooms, the animal room 2 and 3 occurred to be kept dried, and rats of WF-Osaka strain ceased to develop colon carcinomas in the animal room 2. Thereafter, animal room 2 and 3 were adjusted to be kept moistened again. Subsequently WF-Osaka rats in the animal room 2 began to have colon carcinomas in the ascending colon as before, but none of rats developed colon carcinomas in the animal room 3. Based on these findings, we consider that milk factor at the time of foster-breeding played an important role first and high moistened condition of the animal room resulted in promoting effect on colon carcinogenesis on ACI rats and WF-Osaka rats as well.

Adenocarcinoma↗

Induced adenocarcinoma of the ascending colon on LE and Wistar/Shhi rats and virus like particles in the serum of colon cancer carrying WF rats.

Intraperitoneal injection of the serum of colon cancer carrying WF rats induced, within two months, colon carcinomas in the ascending colon of LE and Wistar/Shi rats when they were given it during their suckling. We had also induced colon carcinomas in the ascending colon of ACI rats by the same methods. Therefore, it is supported that this serum derived from colon cancer carrying WF rats must have some transmissible agent in itself. In addition, we ultracentrifuged the serum of cancer carrying WF rats and we found, in the sediment, numerous round or oval virus like corpuscles by electron microscopy studies. Negatively stained corpuscles by phosphotungstic acid staining clearly revealed fine spike appearance on their surface. We believe that these virus like corpuscles are the etiological agent for the transmissible colon carcinoma of WF rat strain.

Adenocarcinoma↗

[Effects of high-dose fentanyl on intraductal pressure in the choledochoduodenal junction in dogs].

Changes in intraductal pressure in choledochoduodenal junction were studied following intravenous administration of fentanyl in dogs. The intraductal pressure was measured with constant-rate infusion method. A statistically significant increase in the intraductal pressure was demonstrated after the intravenous administration of fentanyl 5 micrograms.kg-1 and 75 micrograms.kg-1. The increase in intraductal pressure following fentanyl administration at a dose of 75 micrograms.kg-1 persisted for more than 5 hours. We conclude that in case of intravenous high-dose fentanyl administration special attention should be paid to spasm of choledochoduodenal sphincter.

Animals↗

Spontaneous rupture of hepatocellular carcinoma: a review of 172 Japanese cases.

The spontaneous rupture of a primary hepatocellular carcinoma (HCC) accounts for 10% mortality of HCC patients in Japan. Because this problem occurs much less frequently in western countries, it is often difficult for clinicians practicing in such countries to decide upon the best course of action during the crisis accompanying the spontaneous rupture of a HCC. In an effort to advance the general knowledge of this disease and clarify a selection for its treatment, we review 172 cases of spontaneous rupture of a HCC reported in the Japanese literature. The chief complaint of the patients was sudden epigastralgia or right hypochondriac pain. Abdominal paracentesis was positive in 86% of the patients. Liver failure was the cause of death in 42% of the patients. Therefore, it is important to evaluate liver reserve quickly. In addition, emergency hemostatic procedures must be implemented to avoid hemorrhagic shock. Although two-stage hepatectomy was performed in only 12% of the cases, these had the highest survival rates. Consequently, this is the procedure of choice for the treatment of spontaneous rupture of a HCC.

Adult↗

[Chylothorax developed after cardiac surgery in children: a report of three cases].

Two children developed chylothorax after median sternotomy and a third child developed chylothorax after a Blalock-Taussig operation under the left thoracotomy. The first patient had a closure of ASD and a pulmonary valvotomy and then later developed chylothorax. The thoracic duct was ligated 10 cm just above the diaphragm at 28 days after the first operation because of unsuccessful conservative treatment. The second patient had a Blalock-Taussig operation and the third patient had radical operation for ECD and both developed chylothorax. The latter two patients were cured with conservative treatments such as the administration of Medium Chain Triglyceride or total parenteral nutrition with thoracic drainage. Children who developed chylothorax after cardiac surgery should be treated conservatively for at least the early postoperative period when circulatory and/or respiratory conditions are still unstable.

Child, Preschool↗