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Biomedical subjects

Y Murakami

Publications and source records attributed to Y Murakami.

At least 865 records · Page 48Linked to original sources

Urine growth hormone determinations compared with other methods in the assessment of growth hormone secretion.

Urinary excretion of hGH was studied in children with short stature using a sensitive sandwich enzyme immunoassay technique. Urinary hGH excretion, in terms of hGH: creatinine ratio, showed excellent correlation with the mean and peak hGH values during physiological and pharmacological tests. It seems that the urinary hGH levels reflect serum hGH profiles during the urine collection period. A border zone for the lower limits of normal hGH levels in the urine was 7.5-13.4 ng/g creatinine for the physiological test at night (from 2000 hours to 0600 hours) and 17.4-35.0 ng/g creatinine for the pharmacological tests. Assessment of hGH secretory status by the urinary hGH levels showed good agreement with the serum hGH response. Measurement of urinary hGH could be used as a diagnostic test for impaired hGH secretion, and the multiple blood drawing required in physiological and pharmacological tests might be replaced by urine sampling.

Child↗

Requirement of the Escherichia coli dnaA gene function for ori-2-dependent mini-F plasmid replication.

The mini-F plasmids pSC138, pKP1013, and pKV513 were unable to transform Escherichia coli cells with a dnaA-defective mutation under nonpermissive conditions. The dnaA defect was suppressed for host chromosome replication either by the simultaneous presence of the rnh-199 (amber) mutation or by prophage P2 sig5 integrated at the attP2II locus on the chromosome, both providing new origins for replication independent of dnaA function. The dnaA mutations tested were dnaA17, dnaA5, and dnaA46. dnaA5 and dnaA46 are missense mutations. dnaA17 is an amber mutation whose activity is controlled by the temperature-sensitive amber suppressor supF6. Under permissive conditions in which active DnaA protein was available, the mini-F plasmids efficiently transformed the cells. However, the transformants lost the plasmid as the cells multiplied under conditions in which DnaA protein was inactivated or its synthesis was arrested. As controls, plasmids pSC101 and pBR322 were examined along with mini-F; pSC101 behaved in the same manner as mini-F, showing complete dependence on dnaA for stable maintenance, whereas pBR322 was indifferent to the dnaA defect. Thus, ori-2-dependent mini-F plasmid replication seems to require active dnaA gene function. This notion was strengthened by the results of deletion analysis which revealed that integrity of at least one of the two DnaA boxes present as a tandem repeat in ori-2 was required for the origin activity of mini-F replication.

Bacterial Proteins↗

DNA sequence requirements for replication of polyomavirus DNA in vivo and in vitro.

Cell extracts of FM3A mouse cells replicate polyomavirus (Py) DNA in the presence of immunoaffinity-purified Py large T antigen, deoxynucleoside triphosphates, ATP, and an ATP-generating system. This system was used to examine the effects of mutations within or adjacent to the Py core origin (ori) region in vitro. The analysis of plasmid DNAs containing deletions within the early-gene side of the Py core ori indicated that sequences between nucleotides 41 and 57 define the early boundary of Py DNA replication in vitro. This is consistent with previously published studies on the early-region sequence requirements for Py replication in vivo. Deleting portions of the T-antigen high-affinity binding sites A and B (between nucleotides 57 and 146) on the early-gene side of the core ori led to increased levels of replication in vitro and to normal levels of replication in vivo. Point mutations within the core ori region that abolish Py DNA replication in vivo also reduced replication in vitro. A mutant with a reversed orientation of the Py core ori region replicated in vitro, but to a lesser extent that wild-type Py DNA. Plasmids with deletions on the late-gene side of the core ori, within the enhancer region, that either greatly reduced or virtually abolished Py DNA replication in vivo replicated to levels similar to those of wild-type Py DNA plasmids in vitro. Thus, as has been observed with simian virus 40, DNA sequences needed for Py replication in vivo are different from and more stringent than those required in vitro.

Animals↗

Involvement of hypothalamic growth hormone (GH)-releasing factor in GH secretion induced by intracerebroventricular injection of somatostatin in rats.

Intracerebroventricular (icv) injection of somatostatin-14 (SRIF-14, 5 micrograms/rat) caused an increase in plasma GH in urethane-anesthetized rats and in conscious freely moving rats. Antiserum specific for rat GH-releasing factor (GRF) (0.5 ml/rat, iv) blunted GH release induced by SRIF-14 in these animals. The antiserum also suppressed spontaneous GH surges in conscious rats. In contrast, GH release induced by prostaglandin E2 (5 micrograms/100 g BW, iv) was not affected by the antiserum. SRIF-14 (5 micrograms/rat, icv) also raised plasma GH levels in conscious rats during the constant iv infusion of SRIF-14 (55 ng/55 microliter X min) which suppressed spontaneous GH secretion. Neither plasma TSH levels nor TSH release induced by a TRH analog were affected by icv injection of SRIF-14. These results suggest that the central stimulating effect of SRIF-14 on rat GH secretion is mediated, at least in part, by hypothalamic GRF and not due to a direct action on the pituitary.

Animals↗

Effect of L-threo-3,4-dihydroxyphenylserine (L-DOPS) on catecholamine levels in plasma and cerebrospinal fluid (CSF) in anesthetized rats.

The effect of L-threo-3,4-dihydroxyphenylserine (L-DOPS) on norepinephrine (NE) levels in plasma and CSF was examined in urethane-anesthetized rats. Intravenous injection of L-DOPS (0.5, 1, and 10 mg/100 g body wt) raised plasma NE levels in a dose-related manner whereas CSF NE levels were significantly increased only by the largest dose of L-DOPS. Intracerebroventricular injection of L-DOPS (50 and 250 micrograms/rat) dose-relatedly raised CSF NE levels whereas plasma NE levels were slightly increased by a larger dose of L-DOPS. These findings may indicate that L-DOPS stimulates central noradrenergic mechanisms in the rat although a large dose of L-DOPS is required for peripheral administration.

Animals↗

Studies on beta-lactam antibiotics. I. Synthesis and in vitro anti-pseudomonal activity of 3-isothiazole-cephalosporin derivatives.

The synthesis and in vitro activity of 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2-(2-carboxy-2- alkoxyimino)acetamido]cephalosporins with a (4-carboxy-3-hydroxy-5-isothiazolyl)thiomethyl group at the 3-position are described. These cephalosporins (9a approximately 9i) showed excellent activity against Gram-negative bacteria including beta-lactamase producing strains. The most interesting compound of the series was 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2- (2-carboxy-2-propoxyimino)acetamido]-3-cephem-4-carboxylic acid (9g, YM-13115) because of its outstanding inhibitory potency against Pseudomonas aeruginosa and highly prolonged plasma half-life in rats.

Anti-Bacterial Agents↗

[Right ventricular function in patients with chronic obstructive pulmonary disease measured by krypton-81m].

Right ventricular function was assessed at rest and during exercise in patients with chronic obstructive pulmonary disease (COPD). Right ventricular ejection fraction (RVEF) was measured by first-pass radionuclide angiography using ultrashort-lived radionuclide krypton-81m. The half-life of this nuclide is only 13 sec, and it is completely expired from the lungs. These properties allow measurement of RVEF without correcting for background activity. In 30 patients with cardiac or pulmonary disease, RVEF was first measured by krypton-81 m scintigraphy (Kr-RVEF), then by technetium-99m (Tc-RVEF), without changing the patients' positions. In eight of the 30 cases, right ventricular cineangiography (RVG) was performed within 72 hrs after the radionuclide study, and RVEF was measured according to the Chapman's rule (RVG-RVEF). Kr-RVEF correlated significantly with Tc-RVEF (r = 0.87), and also with RVG-RVEF (r = 0.80). In 10 patients with stable COPD, who had severe hypoxemia (PaO2 less than or equal to 60 mmHg) and pulmonary hypertension [mean pulmonary arterial pressure (mean PAP) greater than or equal to 20 mmHg], and in seven normal control subjects, radionuclide angiographic and hemodynamic monitoring were performed at rest and during supine ergometer exercise. Kr-RVEF at rest was 47.6 +/- 5.4% (mean +/- SD) in patients with COPD and was 54.1 +/- 4.8% in normal subjects. Kr-RVEF during exercise was 51.8 +/- 7.3% in the patients, and 62.3 +/- 3.2% in the normal subjects. Hemodynamically, mean PAP and pulmonary vascular resistance (PVR) increased significantly during exercise, but the RV end-diastolic volume index (RVEDVI) did not change. There was inverse correlation between Kr-RVEF and mean PAP (r = -0.51) or PVR (r = -0.47) as an index of RV afterload. However, there was no correlation between Kr-RVEF and RVEDVI as an expression of RV preload. These findings suggest that a poor response by RVEF during exercise in patients with COPD is associated with elevation of afterload. Thus, right ventricular imaging techniques using the ultrashort-lived nuclide krypton-81 m allow noninvasive, serial and accurate assessments of right ventricular function in patients with COPD.

Aged↗