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Biomedical subjects

R Nakayama

Publications and source records attributed to R Nakayama.

At least 109 records · Page 6Linked to original sources

Kinetic study on disappearance of gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide (DN-1417) from plasma using a radioimmunoassay for DN-1417 isobutylamide.

Kinetic study of disappearance of gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide (DN-1417) from human plasma has been performed by a sensitive and specific radioimmunoassay (RIA) using antiserum against DN-1417 isobutylamide. Antibody against N-[2-hydroxy-4-(isobutylcarbamoyl)butyryl]-L-histidyl-L-prolinamide (DN-isobutylamide) did not cross-react with any other TRH-related peptides tested. DN-isobutylamide was radioiodinated with 125I by the chloramine T method and the product had a specific activity of about 160 microCi/microgram. The sensitivity of the RIA was 50 pg per tube, and the intra- and inter-assay coefficients of variation at concentrations of 1-10 ng/ml were 7.0-11.6%. DN-1417 in the plasma was converted to a stable form, DN-isobutylamide, by incubation with isopropanol-isobutylamine at room temperature for 2 h. DN-Isobutylamide was separated from 2-hydroxy-4-carboxybutyryl-L-histidyl-L-prolinamide (DN-COOH) using a SEP-PAKTM C18 cartridge before RIa. The recovery of DN-isobutylamide from plasma was 86.2-98.2%. The half-life, volume of distribution and plasma clearance rate of DN-1417 examined in 6 normal male volunteers by intravenous injection of 500 micrograms DN-1417 citrate were 11.5 +/- 5.6 min in the first phase and 89.5 +/- 33.5 min in the second phase, 25.3 +/- 10.0 liters and 745.8 +/- 278.6 1/d, respectively. These results indicate that RIA of DN-isobutylamide is useful for analysing DN-1417 metabolism in humans.

Adolescent↗

[Carcinoma of the esophagus engrafted on corrosive stricture of the esophagus].

A highly significant incidence of esophageal cancer engrafted on corrosive stricture of the esophagus has been statistically evaluated. So far, only 8 cases in Japan and over 100 cases in foreign literatures have been reported. In 1976, we reported the first case of carcinoma of the esophagus associated with corrosive stricture of the esophagus in Japan. Our second case operated in 1975 was pathologically confirmed to be adenosquamous carcinoma of the esophagus which has never been reported in the literatures. In this paper surgical and pathological problems of the carcinoma of the esophagus associated with corrosive stricture of the esophagus were discussed adding to the analysis of 8 reported cases in Japan.

Aged↗

Effects of pantolactone and butyrolactone on the pleiotropic phenotypes of lon mutants and on thermal induction of the SOS phenomena in a tif mutant of Escherichia coli K12.

Pantolactone and butyrolactone, known to suppress cell filament formation in the lon mutant of Escherichia coli, were found also to be capable of partially correcting other anomalies of the mutant including impaired lysogenization with bacteriophages lambda and Pl and increased synthesis of colanic acid. In contrast to pantolactone, which inhibited thermal induction of cell filament formation and lambda prophage in the tif mutant as previously described, butyrolactone enhanced these phenomena. It was inferred that whereas these substances exert their effects through acting upon the tif-recA protein in the tif bacterium, there is a distinct target for their characteristic actions in the lon mutant.

4-Butyrolactone↗

Effect of ventricular hypertrophy on conduction velocity of activation front in the ventricular myocardium.

To study the effect of ventricular hypertrophy on conduction velocity of the activation front noninvasively, transmural conduction indexes were obtained from findings of echocardiography and body surface potential mapping performed in 40 patients with right bundle branch block uncomplicated by the left anterior fascicular block. Because in these patients, left ventricular activation proceeds radially without being modified by right ventricular activation, the index was obtained by dividing ventricular septal thickness measured from the echocardiogram by transmural conduction time, which was taken as the time interval from the onset of the QRS complex to the time when the left ventricular epicardial breakthrough minimum appeared on the potential map. The indexes, ranging from 11 to 45 cm/s, has a good positive linear correlation with the septal thickness (Y = 2.37X - 1.33, correlation coefficient [r] = 0.83) and were abnormally small in some failed hearts. Further, both the mean ventricular activation times in lead V5 and the mean value for total duration of left ventricular activation did not differ significantly in patients with and without left ventricular hypertrophy. These findings suggest that conduction velocity was increased in the hypertrophied ventricle and decreased in the failed hearts. Because there were no significant differences in the mean serum sodium and potassium concentrations in the patients with and without left ventricular hypertrophy, it is concluded that hypertrophy itself most likely caused greater conduction velocity. Enlarged cells and multiple intercalated discs abundant in hypertrophied ventricle would have facilitated intercellular current flow and, hence, conduction velocity and impaired cellular connection in the failed heart would have reduced them. Thus, the transmural conduction index is suggested to be an important aid in interpreting electrocardiograms as well as in estimating the pathologic state of the heart.

Adolescent↗

Radioimmunoassay for an analog of thyrotrophin-releasing hormone, gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide (DN-1417).

A heterologous radioimmunoassay method was established to determine plasma levels of gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide (DN-1417). As this compound is unstable in the incubation buffer, we introduced a conversion step. DN-1417 in the plasma was extracted with a solution of isopropanol-isobutylamine (4 : 1) and incubation was performed at room temperature for 2 h for the conversion of DN-1417 into N-[2-hydroxy-4-(isobutylcarbamoyl)butyryl]-L-histidyl-L-prolinamide (DN-isobutylamide). 125I-labeled 2-hydroxy-4-carboxybutyryl-L-histidyl-L-prolinamide and antisera, which was raised in the rabbit using an esterified derivative of DN-1417 conjugated with BSA as an antigen, were used for a sensitive radioimmunoassay of DN-isobutylamide. In this system, 0.2 ng DN-isobutylamide/ml plasma, equivalent to 0.16 ng DN-1417/ml, was detected and there was no apparent interference from its metabolites. The within-assay coefficients of variation were 7.6% at 7.73 ng/tube and 13.7% at 1.32 ng/tube. The between-assay coefficients of variation were 16.1% at 6.43 ng/tube and 12.2% at 1.20 ng/tube. The mean recovery rate of the assay system was 76.0 +/- 3.2% (S.E.M.).

Animals↗

Recombination-deficient mutations and thymineless death in Escherichia coli K12: reciprocal effects of recBC and recF and indifference of recA mutations.

In an approach to characterizing the nature of the lethal event in thymineless death (TLD), rec mutants of Escherichia coli K12 were examined for their sensitivity to TLD. The recB21 and recC22 mutations sensitized cells of the AB1157 line to TLD but not cells of the HF4733 line. This increased sensitivity was not suppressed substantially by either sbcB15 or xonA1 mutation. In contrast, a recF mutation appeared to make cells more resistant to TLD than rec+ cells. Three different recA alleles were shown not to affect TLD appreciably. These results not only provide further support for the view that the site of the lethal event in TLD is cellular DNA, but also strongly suggest the involvement of the recBC and recF gene products in TLD. The apparent indifference of recA mutation implies that the conventional recombination and repair pathways per se are not involved in TLD and that the hypothetical lethal damage to DNA may be unique in nature.

DNA, Bacterial↗

Specific interaction of radioactive anti-androgen TSAA-291 with androgen receptor in rat prostates.

A steroidal anti-androgen ISSA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) bound to a macromolecular component in the cytosol of rat ventral prostates with high affinity (kd = 5.0 X 10-9 M) and in a saturable manner. The number of binding sites was comparable to that for 5 alpha-dihydrotestosterone (5 alpha-DHT). [3H]TSAA-291 binding was effectively displaced by unlabelled 5-alpha-DHT, 19-nortestosterone and cyproterone acetate but to a lesser degree by corticosterone. Glycerol density-gradient centrifugation analysis revealed that the sedimentation coefficient of the [3H]-TSAA-291-macromolecule complex was 3-4.5 S. However, when the unlabelled cytosol was fractionated by glycerol density-gradient centrifugation before the binding of [3H]TSAA-291 was examined, specific binding of [3H]TSAA-291 was observed in fractions corresponding to 8-10 S. Binding of the [3H]TSAA-291-macromolecules complex to prostatic nuclei and DNA-cellulose was considerably less than binding by the [3H]5 alpha-DHT-macromolecule complex. Instability of the TSAA-291 binding component on heat treatment before and after complex formation was also revealed and the results are discussed in terms of the anti-androgenic activity of TSAA-291.

Animals↗

5alpha-reduction of an anti-androgen TSAA-291, 16beta-ethyl-17beta-hydroxy-4-estren-3-one, by nuclear 5alpha-reductase in rat prostates.

Inhibition of 5alpha-reduction of testosterone by an anti-androgen TSAA-291 (16beta-ethyl-17beta-hydroxy-4-estren-3-one) was studied in rat ventral prostates and the metabolic conversion of 3H-TSAA-291 was examined both in vitro and in vivo. In the in vitro experiment using nuclear 5alpha-reductase of the prostate, 5alpha-dihydrostestosterone formation from 3H-testosterone was inhibited in a competitive manner by the anti-androgen. In the in vitro experiment using 3H-TSAA-291, 5alpha-reduction of the anti-androgen occurred. One, 2 and 4 hr after an intravenous administration of 140 muCi/rat of 3H-TSAA-291 to castrated rats, the unchanged TSAA-291 accumulated in higher amounts in the ventral prostate than in the plasma, skeletal muscle and levator ani muscle, thereby indicating the selective uptake of the anti-androgen by the androgen target organ. No appreciable amounts of the 5alpha-reduced metabolite of TSAA-291 were detected in the prostate, thus suggesting that TSAA-291 itself may be responsible for the anti-androgenic properties. The inhibitory potency of the 5alpha-reductase activity of several other 16beta-substituted androstane and estrane analogues was also examined.

5-alpha Reductase Inhibitors↗

A study on the transmural conduction velocity of activation front in the left ventricle of RBBB patients.

To investigate the effect of ventricular hypertrophy on the conduction velocity, the transmural conduction velocity was obtained from the findings of echocardiographic, and body surface potential mapping examinations on 20 RBBB patients. The transmural conduction velocity was linearly correlated with the ventricular septal thickness and the greater the thickness, the faster was the conduction velocity. There was no statistically significant difference in the duration of the left ventricular activation obtained from the mapping examinations as well as in the time of onset of intrinsicoid deflection in V5 between the group of left ventricular hypertrophy and that of non-hypertrophy. There was a good linear correlation between the imaginary distance covered by the activation front which proceeded in the direction from endocardium to epicardium during the left ventricular activation and the ventricular septal thickness. These findings were explicable from the faster conduction velocity in the hypertrophied ventricle. The increase in the conduction velocity in the hypertrophy group would be due to cable characteristics of hypertrophied cardiac cells and also due to increase in the number of multiple intercalated discs in the hypertrophied ventricle. It was concluded that the conduction velocity would be an important information to interpret the ECGs in ventricular hypertrophy as well as to estimate the pathological state of the heart.

Bundle-Branch Block↗