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Biomedical subjects

M Murakami

Publications and source records attributed to M Murakami.

At least 883 records · Page 49Linked to original sources

Parasympatholytic effects of vecuronium are mediated by nicotinic and muscarinic receptors in hearts of anesthetized dogs.

We investigated the blocking effects of vecuronium and pancuronium on the negative chronotropic and dromotropic responses to stimulation of the parasympathetic nerves in the anesthetized, open-chest dog. We stimulated the intracardiac parasympathetic nerves to the SA nodal region (SAP stimulation) or to the atrioventricular nodal region (AVP stimulation). SAP stimulation or AVP stimulation selectively decreased heart rate or increased atrioventricular conduction time, respectively. Vecuronium and pancuronium inhibited the chronotropic response to SAP stimulation and the dromotropic response to AVP stimulation in a dose-dependent manner. The ID50 of each drug for the dromotropic response was less than that for the chronotropic response. The blocking effect of vecuronium on the negative cardiac responses to parasympathetic stimulation was about 10-fold less potent than that of pancuronium. These results suggest that the blocking effects of vecuronium and pancuronium on the negative chronotropic and dromotropic responses to parasympathetic stimulation differ from those of atropine in the heart. In the isolated right atrium perfused with blood from the support dog, vecuronium, injected into the external jugular vein of the support dog, dose-dependently inhibited the negative chronotropic and inotropic responses to carbachol or SAP stimulation and the negative followed by positive chronotropic and inotropic responses to nicotine. The ID50 values for carbachol, nicotine and SAP stimulation were not significantly different. These results suggest that parasympatholytic effects of vecuronium are mediated by not only muscarinic receptors but also neuronal nicotinic receptors in hearts of anesthetized dogs.

Anesthesia↗

[A study of DNA ploidy pattern, proliferation index and PCNA in duodenal carcinoma].

12 cases of duodenal carcinoma were studied for nuclear DNA ploidy patterns, the proliferation index (PI), proliferating cell nuclear antigen (PCNA) positive score (1 = 0-25%, 2 = 26-50%, 3 = 51-75%, 4 = 76-100%) and PCNA positive rate. DNA aneuploidy was observed in 9 cases (75%) and PCNA staining was positive in 11 cases (91.6%). DNA ploidy patterns, PI, PCNA positive scores and positive rates were not related to each other. No relationship DNA ploidy patterns for PCNA positive scores and PCNA positive rates could be found. The relationship between PI and PCNA positive score was found not to be significant (P less than 0.10). PI was revealed to correlate significantly (P less than 0.05) to PCNA positive rate.

Aneuploidy↗

Cardiovascular effects of R- and S-enantiomers of Ro 22-9194, (2R)-2-amino-N- (2,6-dimethylphenyl)-N-[3-(3-pyridyl)propyl]propionamide D-tartrate and (2S)-2-amino-N-(2,6-dimethylphenyl)-N-[3-(3-pyridyl)propyl]propionamide L-tartrate, in dog heart preparations.

A newly synthesized compound, Ro 22-9194, relates in part of to the chemical structure of lidocaine. The cardiac effects of R- and S-enantiomers of Ro 22-9194 were investigated on isolated right atrial and left ventricular (LV) preparations which were cross-perfused with blood from another donor dog and an anesthetized open-chest dog. Each enantiomer (1-1,000 micrograms) decreased dose-dependently the sinus rate and atrial developed tension in the isolated right atrium (RA). The negative chronotropic responses to R- and S-enantiomers were not significantly different, and the negative inotropic responses to R- and S-enantiomers were also generally comparable. Both R- and S-enantiomers (10-3,000 micrograms) also decreased the ventricular developed tension in a dose-related manner similarly. In neurally decentralized, anesthetized, open-chest dogs, R- and S-enantiomers (0.1-3 mg/kg) injected into the femoral vein dose-dependently prolonged atrioventricular (A-V) conduction time and decreased heart rate (HR) and arterial blood pressure (ABP). Each enantiomer (3 mg/kg intravenously, i.v.) prolonged the interval between His bundle and ventricle rather than the interval between atrium and His bundle. There was no significant difference between R- and S-enantiomer-induced negative dromotropic actions. The duration of the negative dromotropic response to each enantiomer (3 mg/kg i.v.) was longer than that of the decrease in BP. These results suggest that the negative chronotropic, inotropic, and dromotropic effects of R- and S-enantiomers of Ro 22-9194 are not stereospecific in dog heart.

Analysis of Variance↗

[Phenylalanine transport in the living human brain by a dynamic PET of L-[2-18F]-fluorophenylalanine].

The transport kinetics of L-[2-18F]-Fluorophenylalanine in the human brain were studied in one normal subject and 6 patients with brain tumor using a dynamic positron emission tomography. The tracer kinetics from blood to brain were described by two compartment model with K1 (influx) and k2 (efflux). The rate constants in normal brain tissue and tumor tissue were K1 = 0.045 ml/g/min, k2 = 0.078 ml/g/min and K1 = 0.122 ml/g/min, k2 = 0.102 ml/g/min, respectively. The Michaelis-Menten constants (Kt and Tmax) for phenylalanine transport in the normal cortex were graphically estimated. The estimated Kt was 35 nmol/ml, whereas the Tmax varied with cerebral blood flow.

Biological Transport↗

[A clinical study of postinfarction angina (PIA): the significance of electrocardiographic ST segment changes during anginal attacks].

We studied the clinical significance of electrocardiographic ST segment changes during PIA attacks. Of 478 AMI patients admitted to the CCU of our hospital within 48 hours after onset, we evaluated 73 (15.3%) with PIA. According to electrocardiographic ST segment changes during PIA attacks, the patients were divided into three groups, namely ST elevation at the same infarction site (same site elevation group), ST depression at the same site (same site depression group), and ST depression at other sites (other site depression group), and their pathological condition was studied. There were 33 patients (45.2%) in the same site elevation group, 19 (26.0%) in the same site depression group, and 21 (28.8%) in the other site depression group. The predominant infarction areas were anteroseptal and inferior wall in the same site elevation group, NTMI in the same site depression group, and inferior wall in the other site depression group. PIA usually occurred within 4 days after the onset of infarction in the same site elevation group, and within 5-7 days in the other site depression group, but no uniform trend was observed in the same site depression group. With respect to the number of vessels showing disease, cases of single-vessel disease tended to predominate in the same site elevation group, while cases of three-vessel disease tended to predominate in the same site depression group and the other site depression group. Stenosis rates in the vessels responsible for infarction were high in the same site elevation group in the acute period. Prognoses were poorest in the same site depression group.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

[A method for measurement of regional cerebral blood flow using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) SPECT; two scans with one point blood sampling technique].

We have developed a new method to quantitate regional cerebral blood flow (CBF) using 123I-IMP and SPECT. This technique requires two SPECT scans and one blood sampling. Based on the 2 compartment model (influx; k1 and outflux; k2), a table between k2 and ratio of 1st scan counts/2nd scan counts was calculated, and a table look up procedure yielded a unique pair of k1 (CBF) and distribution volume (Vd = k1/k2) for each region of interest (ROI). The arterial input function was obtained by one point blood sampling to calibrate the standard input function, which has been obtained from the previous study on 12 subjects. This method was applied to 5 subjects including 1 healthy volunteer and 4 patients with cerebral infarction, and the regional CBF results were compared with those measured by H2(15)O PET technique. Optimized scan time combination was 40, 180 min which provided the best correlation with H2(15)O-CBF. The Vd values obtained in infarcted regions were significantly smaller than those in normal regions, suggesting the importance of measuring Vd for each ROI.

Aged↗

[Analysis of coagulation factor XIII in Crohn's disease--establishment of a novel monoclonal anti-coagulation factor XIII antibody].

A novel monoclonal anti-human coagulation factor XIII (F. XIII) antibody (2C3 antibody) raised in BALB/c mice was established by Kohler and Milstein methods. The monoclonal antibody recognized F. XIII of 85 KD demonstrated by western blotting analysis. Plasma F. XIII-IR levels measured by ELISA with 2C3 antibody were significantly lower in active disease than in quiescent disease in a total of 21 Crohn's disease (CD) patients. Plasma F. XIII levels were significantly lower on admission in CD with fistulas than in CD without fistulas. Relationships between activities of CD and plasma F. XIII levels were shown. No significant relationships, however, were observed between F. XIII-IR levels and nutritional states assessed by TP, ALB, TF, PA, RBP, %IBW. Low levels of F. XIII in active CD patients with fistulas may occur regardless of hyponutrition. By using 2C3 antibody, global functions of F. XIII will become clarified as well as pathologic and diagnostic roles of plasma F. XIII in CD.

Adolescent↗

[Quantification of regional cerebral blood flow (rCBF) measurement with one point sampling by 123I-IMP SPECT].

A handy method of quantifying regional cerebral blood flow (rCBF) measurement by 123I-IMP SPECT was designed. A standard input function was made and the sampling time to calibrate this standard input function by one point sampling was optimized. An average standard input function was obtained from continuous arterial samplings of 12 healthy adults. The best sampling time was the minimum differential value between the integral calculus value of the standard input function calibrated by one point sampling and the input function by continuous arterial samplings. This time was 8 minutes after an intravenous injection of 123I-IMP and an error was estimated to be +/- 4.1%. The rCBF values by this method were evaluated by comparing them with the rCBF values of the input function with continuous arterial samplings in 2 healthy adults and a patient with cerebral infarction. A significant correlation (r = 0.764 (p less than 0.001)) was obtained between both.

Adult↗

[Cerebral blood flow dynamics in fetus].

In order to obtain quantitative data concerning the changes of fetal cerebral blood flow occurring in relation to hypoxia and acidemia, we evaluated correlations between fetal blood gases and blood flow velocity waveforms in fetuses. A total of 24 Doppler examinations were carried out to investigate the waveforms of middle cerebral and umbilical arteries in 17 intrauterine growth retardation (IUGR) fetuses. Within 24 hours after blood flow measurements, cordocentesis was performed and umbilical venous blood gases and pH were determined. There was a significant positive correlation between the gestationally adjusted resistance index value [delta SD (RI)] for middle cerebral artery and PO2 or pH, while a negative correlation was noted between the middle cerebral artery delta SD (RI) and PCO2. The umbilical artery delta SD (RI) and pH showed a negative correlation, but there was no correlation between the umbilical artery delta SD (RI) and PCO2 or PCO2. In the presence of partly compensated respiratory acidosis, the delta SD (RI) for middle cerebral artery was still high, while that for umbilical artery did not increase although PO2 was reduced. These findings suggest that blood flow changes in fetal middle cerebral and umbilical arteries are different in IUGR. Middle cerebral artery blood flow may respond directly to changes in PO2. Furthermore, fetal acid-base disorders may modify the relationship between blood flow changes and fetal PCO2.

Acid-Base Equilibrium↗

[Arterial clearance and cerebral uptake of Tc-99m ECD in patients with cerebrovascular disease compared with PET].

Technetium-99m ethyl cysteinate dimer (ECD) has recently developed for SPECT imaging in assessment of cerebral perfusion. We evaluated the arterial blood clearance and the regional brain uptake of Tc-99m ECD compared with the regional CBF measured by PET in patients with cerebrovascular disease. Nine patients with diagnosis of cerebral ischemic disorders (N = 7) and cerebral hemorrhage (N = 2) were studied. PET study was performed with HEADTOME IV by O-15 steady state inhalation method. Immediately after the PET study, 555-740 MBq (5-20 mCi) of Tc-99m ECD was injected intravenously. After injection arterial blood sampling was performed sequentially, and we separated lipophilic fraction from whole blood using ethyl acetate in two cases. The SPECT imaging with Tc-99m ECD (ECD-SPECT) was started 5 min (first imaging) and 60 min (second imaging) after the administration using a high resolution ring type SPECT system (HEADTOME II). Several ROIs were placed on practically the same anatomical location on both SPECT and PET images. Clearance of the tracer in arterial whole blood and lipophilic fraction was rapid. Concerning to the distribution pattern of ECD-SPECT images there was no differences between the 1st imaging and the 2nd imaging, although about 15% of diffuse decrease of Tc-99m ECD uptake was shown in the 2nd images. The brain distribution of ECD-SPECT was comparable to the pattern of CBF image by PET. The regional relative counts of ECD-SPECT corresponded closely to the CBF value by PET, but it was no linear correlation between brain uptake of ECD-SPECT and PET-CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Seizure-inducing factors in the patients with childhood epilepsy].

We evaluated the seizure-inducing factors in 264 patients with childhood epilepsy. One hundred and thirty-six patients (51.5%) exhibited some kind of inducing factors. Non-specific inducing factors were commonly recognized, such as "febrile state" (29.2%), "fatigue after exercise" (15.2%), "sleep disturbance" (9.1%), "psychic stress" (8.3%) and "emotional change" (6.8%). Specific inducing factors, which related to reflex epilepsy, was recognized in only 7 patients. "Febrile state" was dominant in young children, but the other nonspecific inducing factors were dominant in adolescent. Incidences and kinds of inducing factors also related to the epileptic syndromes an seizure prognosis. The patients with symptomatic partial epilepsies (64.3%) and grand mal on awakening (85.7%) had significantly more inducing factors, and the patients with refractory seizures had a higher incidence and more variable kinds of inducing factors than the patients with well-controlled seizures. These results suggest that seizure-inducing factors are recognized in children as well as in adults, and the clarification of inducing factors is important to the management of epilepsy, particularly of intractable epilepsy.

Adolescent↗

Alterations in sex hormones and sexual function of patients with renal failure treated with recombinant human erythropoietin.

Since it has been reported that correction of anemia in long-term hemodialysis patients by using human recombinant erythropoietin (r-HuEPO) is associated with improve sexual function, we conducted the present study to evaluate the changes in sex hormones as well as sexual function after r-HuEPO administration (1500 to 4500 IU per dialysis) for a year in patients on regular hemodialysis. Thirteen patients receiving regular hemodialysis entered this study. Their median age was 43 years. Along with correction of anemia (the hematocrit increased from 20 to 28%), testosterone (T) increased from 2.4 +/- 0.1 to 2.6 +/- 0.2 ng/ml, follicular stimulating hormone (FSH) increased (29 +/- 5 to 73 +/- 7 mIU/ml), luteinizing hormone increased (69 +/- 14 to 160 +/- 21 IU/ml) and prolactin decreased (all changes are significant at p less than 0.05). However, the improvement of sexual function was not remarkable. Only 25% of the uremic patients treated with r-HuEPO showed amelioration of this function. From the present data, it does not seem likely that therapy with r-HuEPO induces directly amelioration of sexual function through changes in sex hormones.

Adult↗

Group II phospholipase A2 inhibitors suppressed lysophosphatidylserine-dependent degranulation of rat peritoneal mast cells.

Rat peritoneal mast cells were sensitized with IgE and challenged with the specific antigen in the presence of lysophosphatidylserine (lysoPS), an essential co-factor for rodent connective tissue mast cell degranulation, and the effects of phospholipase A2 inhibitors were examined. Mepacrine, a known inhibitor of phospholipase A2, at concentrations below 10(-5) M and anti-rat 14-kDa group II phospholipase A2 antibody inhibited histamine release, while they did not affect the prostaglandin generation. Like histamine release, prostaglandin generation in IgE- and antigen- challenged rat peritoneal mast cells was dependent on the presence of lysoPS. These results indicate that 14-kDa group II phospholipase A2 may play an essential role in IgE-, antigen-, and lysoPS-dependent degranulation process of rat peritoneal mast cells and that the mechanism whereby it participates may not be due to the production of lysoPS from PS in mast cell membranes.

Animals↗

Critical cytoplasmic region of the interleukin 6 signal transducer gp130 is conserved in the cytokine receptor family.

Interleukin 6 (IL-6) signal is transduced through gp130 that associates with a complex of IL-6 and IL-6 receptor. Truncations or amino acid substitutions offe introduced in the cytoplasmic region of human gp130, and the mutant cDNAs were transfected into murine interleukin 3-dependent cells to determine amino acid residues critical for generating the IL-6-mediated growth signal. In the 277-amino acid cytoplasmic region of gp130, a 61-amino acid region proximal to the transmembrane domain was sufficient for generating the growth signal. In this region, two short segments were significantly homologous with other cytokine-receptor family members. One segment is conserved in almost all members of the family, and the other is found especially in granulocyte colony-stimulating factor receptor, interleukin 2 receptor beta chain, erythropoietin receptor, KH97 (a granulocyte/macrophage colony-stimulating factor receptor-associated molecule), and interleukin 3 receptor. gp130 molecules with mutations in either of these two segments could not transduce growth signal. Loss of signal-transducing ability of gp130 with such a mutation coincided with disappearance of IL-6-induced tyrosine phosphorylation of gp130.

Amino Acid Sequence↗

Eicosanoid generation from antigen-primed mast cells by extracellular mammalian 14-kDa group II phospholipase A2.

The extracellular form of 14-kDa group II phospholipase A2 has been found to accumulate at various types of inflammatory sites. In the present paper, we have studied the possible role of the extracellular 14-kDa group II phospholipase A2 in the process of prostaglandin production in activated rat mast cells. When mast cells obtained from the peritoneal cavity of rats were sensitized with IgE, challenged with antigen and then exposed to extracellular 14-kDa group II phospholipase A2, appreciable release of prostaglandin D2 was observed. Generation of prostaglandin D2 was dependent on the concentration of the phospholipase A2 as well as that of the antigen, while no appreciable prostaglandin D2 generation was observed with cells in the absence of the antigen. No histamine release was observed under the same conditions. Phosphatidylcholine in mast cell membranes was appreciably hydrolyzed to liberate free arachidonic acid when mast cells were incubated with 14-kDa group II phospholipase A2 added exogenously in the presence of the antigen. Both the generation of prostaglandin D2 and the release of arachidonic acid were retarded by inhibitors specific to 14-kDa group II phospholipase A2. Thus, 14-kDa group II phospholipase A2 may function in the process of inflammation by acting on IgE-antigen-primed mast cells, which are not fully activated, to generate eicosanoids.

Animals↗

Specification of small distal 6q deletions in two patients by gene dosage and in situ hybridization study of plasminogen and alpha-L-fucosidase 2.

Gene-dosage and in situ hybridization study of plasminogen (PLG) and alpha-L-fucosidase 2 (FUCA2) was performed on two patients with a small deletion of the distal long arm of chromosome 6, to define the structural abnormality more precisely. The results led to the cytogenetic diagnosis of an interstitial 6q deletion, del(6)(q25.1q25.3), in one patient and of a terminal 6q deletion resulting from a paternal t(1;6)(q44;q2605) translocation in the other patient. The latter patient had congenital noncommunicating hydrocephalus due to obstruction at the level of the foramen of Monro or the third ventricle which has not previously been described in terminal 6q deletions. Review of the literature suggests the emergence of a clinical syndrome associated with terminal 6q deletions.

Abnormalities, Multiple↗