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Biomedical subjects

Y Miyagi

Publications and source records attributed to Y Miyagi.

At least 145 records · Page 8Linked to original sources

Effects of diltiazem and verapamil on (+)-PN 200-110 binding kinetics in dog cardiac membranes.

The effects of d-cis-diltiazem (diltiazem) and verapamil on 1,4-dihydropyridine binding to dog cardiac membranes were studied in competition, saturation and kinetic binding experiments with [3H](+)-PN200-110. Diltiazem increased [3H](+)-PN200-110 binding with an observed maximal effect at 50 microM, while verapamil decreased [3H](+)-PN200-110 binding in a dose-dependent manner. Scatchard analysis of saturation binding data revealed that diltiazem (50 microM) increased the maximal binding site density and verapamil (100 microM) increased the dissociation constant (KD) of [3H](+)-PN200-110 binding. The kinetic experiments demonstrated that diltiazem significantly reduced both the association and the dissociation rate of [3H](+)-PN200-110 binding, resulting in no significant change in the apparent KD. In contrast, verapamil accelerated dissociation and slowed down association of [3H](+)-PN200-110 binding. Diltiazem appears to alter both the number of [3H](+)-PN200-110 binding sites and the characteristics of [3H](+)-PN200-110 binding.

Allosteric Regulation↗

A correlation between IgG class antibody production and glomerulonephritis in the murine chronic graft-versus-host reaction.

A graft-versus-host reaction (GVHR) was induced in (B10 x DBA/2)F1 (BDF1) and (BALB/c x A)F1 (CAF1) murine recipients by injection of their parental or B10.D2-derived spleen cells. The incidences of glomerulonephritis and autoantibody production were then correlated. All of the BDF1 mice that received DBA/2 spleen cells (termed DBA/2----BDF1) and 33% of the CAF1 mice that received BALB/c spleen cells (BALB/c----CAF1) developed glomerulonephritis. However, in other combinations (B10.D2----BDF1, A/J----CAF1) no significant glomerular lesions were observed. An analysis of antibodies by ELISA revealed that the groups with renal disease showed a significant polyclonal elevation of IgG class antibodies, including autoantibodies (anti-DNA, anti-MRBC, and NTA) and a conventional antibody (anti-TNP-KLH). No significant IgG class antibody production was observed in the groups that did not develop glomerulonephritis. Thus, it was suggested that an IgM to IgG class switch is important in the development of glomerulonephritis in GVHR. Other factors also appear to be involved. Only 33% of BALB/c----CAF1 developed glomerulonephritis, even though a level of IgG class antibody production was comparable to that observed in DBA/2----BDF1 in which 100% showed severe glomerulonephritis.

Animals↗

Glomerulonephritis induced by murine chronic graft-versus-host reaction.

Severe glomerulonephritis was induced successfully in (B10 x DBA/2)F1 (BDF1) mice by injection of parental DBA/2 lymphoid cells. The mice manifested typical nephrotic syndrome dying around 10 weeks post injection. Electron microscopical examination demonstrated electron dense deposits first in the mesangial matrix, then in the subepithelium compatible with immune complex glomerulonephritis. Subendothelial deposits were not observed. Immunofluorescent study revealed IgG deposition in the capillary wall and IgM in the mesangium early in the process. As the lesion progressed, both IgG and IgM were present in the mesangial area and along the capillary wall. Some glomeruli showed segmental mesangiolysis, suggesting that altered mesangial cells have a role in the development of glomerular change, which together with rise in serum anti-DNA antibody titer suggest that autoantibodies promote the glomerular lesions in this model system.

Animals↗

Characterization of experimental rat nephroblastoma and its cell line.

Rat nephroblastoma (Wilms' tumor) was induced by transplacental administration of N-ethyl-nitrosourea (ENU). The induced renal tumors were histologically compatible with human nephroblastoma. A cultured cell line (ENU-T-1) established from a xenotransplant, showed similar morphological and biological features to cultured embryonal kidney cells. Introduction of normal human chromosome #11 (#11) bearing Wilms' tumor suppressor gene(s) (WT) suppressed colony-forming ability on soft agar plates (CFA) but tumorigenicity of ENU-T-1 was not affected. Whereas tumorigenicity of human nephroblastoma cell line, SK-NEP-1 was completely suppressed, CFA was unchanged. These facts indicated that pathogenetic mechanism is different between human and experimental rat nephroblastomas.

Animals↗

Functional expression of the alpha 1 subunit of the AMPA-selective glutamate receptor channel, using a baculovirus system.

Using a baculovirus expression vector system, the alpha 1 subunit of the mouse AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)-selective glutamate receptor channel was expressed in insect Spdoptera frugiperda cells. Binding studies using [3H]AMPA showed that insect cells infected with the recombinant virus expressed approximately 1.8 x 10(5) binding sites per cell on their surface. The ligand binding characteristics of the receptors expressed in insect cells were examined. The baculovirus-insect cell expression system affords high-efficiency expression of the receptor in sufficient amounts to permit structural and functional analyses.

Animals↗

Detection of elastase production in Escherichia coli with the elastase structural gene from several non-elastase-producing strains of Pseudomonas aeruginosa.

The elastase structural gene from Pseudomonas aeruginosa IFO 3455 has been cloned and sequenced. Using this gene as a probe, we cloned the DNA fragments (pEL3080R, pEL10, and pEL103R) of the elastase gene from non-elastase-producing strains (P. aeruginosa IFO 3080, N-10, and PA103 respectively). These three Pseudomonas strains showed no detectable levels of elastase antigenicity by Western blotting (immunoblotting) or by elastase activity. When elastase structural genes about 8 kb in length were cloned into pUC18, an Escherichia coli expression vector, we were able to detect both elastase antigenicity and elastolytic activity in two bacterial clones (E. coli pEL10 and E. coli pEL103R). However, neither elastolytic activity nor elastase antigenicity was detected in the E. coli pEL3080R clone, although elastase mRNA was observed. The partial restriction map determined with several restriction enzymes of these three structural genes corresponded to that of P. aeruginosa IFO 3455. We sequenced the three DNA segments of the elastase gene from non-elastase-producing strains and compared the sequences with those from the elastase-producing P. aeruginosa strains IFO 3455 and PAO1. In P. aeruginosa N-10 and PA103, the sequences were almost identical to those from elastase-producing strains, except for several nucleotide differences. These minor differences may reflect a microheterogeneity of the elastase gene. These results suggest that two of the non-elastase-producing strains have the normal elastase structural gene and that elastase production is repressed by regulation of this gene expression in P. aeruginosa. Possible reasons for the lack of expression in these two strains are offered in this paper. In P. aeruginosa IFO 3080, the sequence had a 1-base deletion in the coding region, which should have caused a frameshift variation in the amino acid sequence. At present, we have no explanation for the abnormal posttransciptional behavior of this strain.

Amino Acid Sequence↗

Different usage of two polyadenylylation signals in transcription of the N-myc gene in rat tumor cells.

The complete nucleotide sequence of a rat genomic DNA fragment of 6.9 kbp containing the entire N-myc gene was determined. A unique structural feature of the rat N-myc gene is the presence of two polyadenylation signals in the exon 3 region resulting in formation of two poly(A)+ N-myc mRNAs of 2.9 and 2.2 kb length. Elevated expression of the 2.9 kb mRNA, which was not due to gene amplification, was observed in normal rat tissues such as brain, adrenal and testis, and in rat tumor cells such as ascites hepatoma AH130, AH70Btc and AH7974 cells, and pituitary tumor GH3 cells. In contrast, expression of 2.2 kb mRNA, for which transcription was terminated at the upstream polyadenylation site, was observed only in GH3 cells.

Adrenal Glands↗

Comparative hemodynamic effects of intravenous dobutamine and dibutyryl cyclic AMP, a new inotropic agent, in severe congestive heart failure.

In nine patients with chronic congestive heart failure, the acute hemodynamic response to intravenous (i.v.) dibutyryl cyclic AMP (DBcyclicAMP) administration was compared with i.v. dobutamine administration. Both agents led to a significant and similar increase in cardiac index. Dobutamine caused a significant increase in mean arterial pressure but did not produce a significant change in pulmonary capillary wedge, mean pulmonary artery, or mean right atrial pressures. In contrast, DBcyclicAMP caused a significant decrease in mean arterial, mean pulmonary capillary wedge, mean pulmonary artery, and mean right atrial pressures, reflecting vasodilator activity. The fall in systemic vascular resistance was larger after DBcyclicAMP than after dobutamine. DBcyclicAMP achieves an optimal improvement in cardiovascular hemodynamics in concert with substantial vasodilating effect. This pharmacologic action constitutes the mainstay of i.v. therapy for severe congestive heart failure (CHF).

Adult↗

Relation of exercise capacity to resting arterial oxygen transport in left ventricular dysfunction.

To determine the relation between arterial oxygen delivery and exercise capacity, 38 men with mild to severe chronic left ventricular (LV) dysfunction (New York Heart Association functional class II or III) were studied. All diagnostic cardiac catheterizations were performed 1 week before the exercise tests and the mean LV ejection fraction was 0.30 +/- 0.07. All patients performed graded treadmill exercise tests according to the Sheffield protocol. The relation between supine resting hemodynamic measurements did not correlate with exercise duration. Only resting cardiac output (r = 0.54, p less than 0.01) and systemic vascular resistance (r = -0.51, p less than 0.05) correlated weakly with exercise duration. However, arterial oxygen transport was highly related to exercise duration (r = 0.76, p less than 0.001) and peak oxygen consumption (r = 0.71, p less than 0.001). Thus, knowledge of calculated arterial oxygen transport can predict exercise capacity in patients with chronic LV dysfunction.

Adult↗

Effects of DBcAMP on exercise capacity in patients with and without chronic heart failure.

The acute effects of vasodilation on exercise capacity in cardiac patients with (group 1) and without (group 2) congestive heart failure were studied using dibutyryl cyclic AMP (DBcAMP). Exercise was performed on an upright bicycle ergometer using a graded protocol. DBcAMP increased cardiac output and decreased pulmonary capillary wedge pressure and systemic vascular resistance both at rest and during maximal exercise in these two groups. However, before and after DBcAMP neither exercise duration (371 +/- 52 seconds vs. 388 +/- 44, NS, in group 1, 645 +/- 148 vs. 635 +/- 143 seconds, NS, in group 2, respectively) nor maximal oxygen consumption (12.8 +/- 2.3 ml/kg/min vs. 13.1 +/- 1.6, NS, in group 1, 20.3 +/- 1.4 vs. 20.1 +/- 1.5, NS, in group 2, respectively) was improved. In both groups the arteriovenous oxygen differences were lower at rest and during exercise performed while on DBcAMP than in the control state. In group 2 patients excess vasoconstriction mediated by abnormally increased neurohormonal activities or edema were absent. Failure of the vasodilator to increase exercise capacity is probably due to nonspecific vasodilation and maldistribution of increased cardiac output, and not to tight vasoconstriction or narrowed arteriolar lumen.

Adolescent↗

[Induction of coronary arterial spasm by intracoronary administration of acetylcholine in patients with vasospastic angina].

To examine whether intracoronary injections of acetylcholine induce coronary artery spasm in patients with vasospastic angina, incremental doses (20, 30 and 50 micrograms) were injected directly into the coronary arteries in 12 patients with variant angina (Group A: rest angina with electrocardiographic ST-segment elevation during attacks), 19 with vasospastic angina (Group B: rest angina and/or effort angina with variable threshold in the treadmill exercise stress test), 11 with organic coronary artery stenosis but without angina (Group C), and 14 without coronary artery disease (Group D). A temporary cardiac pacemaker was positioned in the right ventricle. Coronary artery spasm was defined as severe vasoconstriction (greater than or equal to 90% of reduction in the luminal diameter) with chest pain and/or ischemic changes in the electrocardiogram. Intracoronary injection of acetylcholine induced spasm of at least one coronary artery in all 12 patients (100%) of Group A, in 18 (95%) of Group B, in two (18%) of Group C, and in two (14%) of Group D. Thus, the sensitivity of this method for inducing coronary spasm was 100% in group A, 95% in Group B, and 97% in Group A plus Group B. The specificity for inducing spasm was 86% in Group D, and 84% in Group C and Group D. When acetylcholine was injected separately into the left and right coronary arteries, spasm of both the coronary arteries was observed in two (40%) of Group A, in five (33%) of Group B, and none (0%) of Group C and Group D. Acetylcholine (20 micrograms) induced coronary spasm in 10 (83%) of Group A and only in nine (47%) of Group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Plaque rupture possibly induced by coronary spasm--an autopsy case of acute myocardial infarction.

The histological picture of sites of coronary spasms has not yet been made sufficiently clear. A histopathological examination was performed on the coronary artery of a patient who died of acute myocardial infarction after a refractory coronary spasm was identified by coronary arteriography. In the site of the coronary spasm, intimal bleeding as well as infiltration by lymphocytes and plasma cells in the adventitia were seen. In the same region, fracture of intimal collagen fibers and rupture of atheromatous plaque were observed. Although it is very difficult to prove in individual cases of acute myocardial infarction that spasms played a part, some cases involving spasms may possibly exist among the cases of acute myocardial infarction showing atheromatous plaque rupture--thrombus formation.

Coronary Angiography↗

[Evaluation of coronary blood flow using digital subtraction technique and cine coronary angiography: a preliminary report].

To evaluate coronary circulation in ischemic heart disease, digital image processing with cine coronary angiography was performed. Using time-density curves obtained from individual pixels, images showing the distribution of contrast density and transit time were obtained. To record angiograms, contrast medium was injected into the coronary artery in a steady manner during right atrial pacing. Frames in the end-diastolic phase immediately before the P wave were selected, and digitized into a 512 x 512 x 8 bit matrix using a system composed of a video camera, an analog-to-digital converter, and a computer. These digitized images were then stored in a disk memory. A mask image was prepared before the injection of contrast medium. Subtraction was performed using the mask image and a series of images following contrast injection. The subtracted images were of sufficient quality to permit clear observation of the individual coronary arterial branches. Time-density curves were then determined from these subtracted images. From these curves, time from the onset of contrast injection to its peak density (Tp), time from the peak density to the half peak density (T 1/2) and the attenuation factor of the curves (tau) were derived. Their distributions were expressed as color images. Examples of a normal control and a case of inferior infarction were demonstrated. Blood flow function images with good spatial resolution were thus obtained. This method is useful for evaluating coronary blood flow.

Angioplasty, Balloon↗

[Pharmacokinetics of carboplatin (CBDCA) and tissue concentration of platinum in gynecologic organs].

A pharmacokinetics and platinum concentration in the gynecologic organs were measured following the intravenous drip infusion of 375 mg/m2 of CBDCA. Total platinum (TP) in plasma decreased biphasically and free platinum (FP) was almost monophasically eliminated. The t 1/2 of FP was about 51 min. and the percentage of FP out of TP at four hours after administration was more than 92%, which was much higher proportion compared with that of cisplatin (CDDP). A cumulative excretion of platinum in the urine within 24 hours was 69%. The platinum concentration in the benign part of portio and endocervix were higher than that of malignant portion, although there were no significant differences in other pelvic organs such as ovary and tubes. However, pelvic lymph-nodes showed less platinum concentration both in metastatic and non-metastatic tissues. Platinum concentration in the tissue did not change significantly with lapse of time. Bone marrow suppression was observed especially in the patients who had received chemotherapy or radiotherapy. No renal toxicity was observed even without any hydration and gastro-intestinal toxicity was much milder than that of CDDP.

Antineoplastic Agents↗

Serum beta-enolase in acute myocardial infarction.

The enzyme beta-enolase (alpha beta and beta beta forms) is present in skeletal and heart muscle and catalyses the glycolysis of 2-phosphoglycerate to phosphoenolpyruvate. The enzyme was measured in serum samples from patients with acute myocardial infarction, angina pectoris, congestive heart failure, and idiopathic cardiomyopathy. Serum concentrations of beta-enolase were significantly increased in acute myocardial infarction but not in the other cardiovascular diseases. Activity peaked approximately 12 to 14 hours after an acute attack of chest pain, and then gradually decreased as the patient recovered. The rise and fall in beta-enolase concentration were faster and steeper than those of creatine kinase activity, particularly in patients in whom activities of both these enzymes were less high. The assay of beta-enolase, which is highly specific and sensitive, has considerable advantages for the early diagnosis of myocardial infarction and the diagnosis of a second episode of myocardial infarction because beta-enolase concentration increases very early and rapidly and clears quickly. These data imply that serum beta-enolase may be a more effective marker for early myocardial infarction, particularly in milder cases, than measurement of creatine kinase activity.

Adult↗