PubMed Health⌕ Search

Biomedical subjects

H Seto

Publications and source records attributed to H Seto.

At least 199 records · Page 11Linked to original sources

Importance of abnormal lung perfusion in excessive exercise ventilation in chronic heart failure.

Whether excessive ventilatory response to exercise is related to the maldistribution of pulmonary blood flow was examined in 23 patients with chronic heart failure and nine age-matched normal subjects. With the use of technetium 99m macroaggregated albumin, the resting distribution of pulmonary blood flow was assessed by the scintigraphic counts ratio of upper to lower lung fields. The ventilatory response to exercise was assessed by the slope of the relationship between minute ventilation and carbon dioxide production during exercise. Eight patients (group A) had slope less than 33, the upper limit of the normal range, and 15 patients had slope of 33 or greater (group B). In group B pulmonary blood flow was distributed more to the upper lung, which made the counts ratio (60%) higher than in normal subjects (34%) or in patients in group A (38%). There was no significant difference in pulmonary flow distribution between normal subjects and patients in group A. In group B tidal volume did not increase during exercise as much as it did in normal subjects and in patients in group A; therefore, the respiratory pattern was rapid and shallow. Although the ratio of physiologic dead space to tidal volume fell by 20% during exercise in normal subjects and by 23% in patients in group A, it failed to decrease in patients in group B (-1%), which indicates a relative increase in dead space respiration during exercise. These data indicate that decreased lung compliance and regional ventilation-perfusion mismatch caused by pulmonary vascular and parenchymal abnormalities would play an important role in the excessive exercise ventilation in chronic heart failure.

Exercise Test↗

Simultaneous measurements of twenty-four-hour whole-body retention of 47Ca-chloride and 99mTc-MDP: early differentiation of metabolic bone diseases in rat models.

The 24-h whole-body retention (24-h WBR) of 47Ca-chloride and 99mTc-MDP was measured in four rat models over a 6-week period at 2 week intervals. Fine detail bone radiographs of the femurs and histologic bone specimens were also obtained simultaneously. In the osteomalacic (M) and steroid-induced osteoporotic (S) groups the 24-h WBR values of 47Ca were significantly lower, and in the osteoporotic (P) group were higher than in the control (C) group from the second week. The 24-h WBR values of 99mTc-MDP were significantly higher in the M group and were lower in the S group from the second week. Simultaneous measurements of 24-h WBR of these two radiopharmaceuticals facilitated the early differentiation of metabolic bone diseases in the animal models prior to the detection of radiologic bone changes.

Animals↗

Regional distribution of 201Tl during one-leg exercise: comparison with leg blood flow by plethysmography.

To validate the use of 201Tl distribution as an estimate of regional blood flow in the legs, 201Tl leg uptake was compared by whole body scintigraphy and simultaneously measured leg blood flow by plethysmography during one-leg exercise in 11 male subjects. 201Tl leg uptake ratio and leg blood flow ratio were also compared to exclude the effect of cardiac output variation in each subject. There was a good correlation between 201Tl leg uptake and leg blood flow (r = 0.85, P < 0.01, y = 0.28x + 1.00). Moreover, there was a highly linear correlation between these ratios (r = 0.98, P < 0.01, y = 0.75x + 0.13), although the 201Tl leg uptake ratio somewhat underestimated the leg blood flow ratio as exercise became strenuous. It is concluded that 201Tl leg uptake reflects regional blood flow in the legs during exercise.

Aged↗

Ventriculolumbar perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosou rea hydrochloride.

We report on the toxicity, intrathecal pharmacokinetics, and therapeutic effect of the ventriculolumbar perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitros our ea hydrochloride (ACNU) against the subarachnoid dissemination of primary central nervous system tumors. Fifteen patients received ventriculolumbar perfusion of ACNU. One was treated with ventriculolumbar perfusion of ACNU alone, and the others underwent concomitant systemic chemotherapy; three of these patients received irradiation as well. ACNU was administered at an initial dose of 0.5 and was increased to 1.5 to 10.0 mg in six patients. Because of a lack of Level 2 or greater toxicity, the subsequent seven patients received 8.7 to 10.0 mg of ACNU dissolved in artificial cerebrospinal fluid (CSF) at a concentration of 0.1 mg/ml, from the start of the treatment. During ACNU administration, the lumbar CSF was drained at approximately the same rate as that of the infusion. Twelve patients received from 3 to 42 courses (average, 14 courses). The cumulative dose of ACNU ranged from 5 to 330.4 mg (average, 82.9 mg). One patient had a convulsion; two patients experienced transient headache, nausea, and vomiting; two others reported transient headache, nausea, vomiting, and fecal incontinence; and one experienced transient nausea, vomiting, and fecal incontinence. No side effects were noted in the other nine patients. When 9.0 to 9.5 mg of ACNU, dissolved in 90 to 95 ml of artificial CSF, was administered for 37 to 52 min, the maximum concentration of ACNU in the lumbar CSF was 9.86 to 12.79 micrograms/ml and the area under the drug concentration-time curve was 260.8 to 502.5 micrograms.min/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Tetronothiodin, a novel cholecystokinin type-B receptor antagonist produced by Streptomyces sp. NR0489. II. Isolation, characterization and biological activities.

A novel cholecystokinin type-B receptor antagonist named tetronothiodin has been isolated by column chromatography and preparative HPLC from the fermentation broth of Streptomyces sp. NR0489. Tetronothiodin inhibited the binding of CCK8 (C-terminal octapeptide of cholecystokinin) to rat cerebral cortex membranes (CCK type-B receptors) with an IC50 of 3.6 nM, whereas it did not inhibit CCK8 binding to rat pancreatic membranes (CCK type-A receptors). It also inhibited CCK8 induced Ca2+ mobilization in GH3 cells, a rat anterior pituitary cell line, but was without effect on the basal cytosolic Ca2+ concentration. This finding indicated tetronothiodin was an antagonist of CCK type-B receptors.

Animals↗

Studies on cell growth stimulating substances of low molecular weight. Part 2. Exfoliazone and lavanducyanin, potent growth promoting substances of rat liver cell line, RLN-8, produced by Streptomyces exfoliatus and Streptomyces aeriouvifer.

Exfoliazone and lavanducyanin isolated from Streptomyces exfoliatus BT-38 and Streptomyces aeriouvifer CL-190, respectively, showed strong growth promoting activities to liver cell RLN-8 established from normal Donryu rat. When RLN-8 cells were cultured in Eagle's minimal essential medium containing 1% fetal bovine serum, exfoliazone significantly stimulated the growth of RLN-8 cells. However, no effect was observed under serum-free conditions. Effective dose of exfoliazone was at the range of 0.004-0.1 microgram/ml. Cell proliferation was confirmed by MTT assay and by the increases of cell number and DNA synthesis. Lavanducyanin also stimulated the growth of RLN-8 cells in the same medium. It showed growth promoting activity at lower concentrations than exfoliazone and the effective dose was at the range of 0.0001-0.06 microgram/ml. Analogous compounds of exfoliazone and lavanducyanin also promoted the growth of RLN-8 cells. In addition, exfoliazone and lavanducyanin enhanced the growth of NIH 3T3 and T601 cells. These results indicate that exfoliazone, lavanducyanin and their related compounds seem to be a new type of growth promoting substances with low molecular weight produced by microorganisms, and that they can partially substitute for functions of serum. Since 12-O-tetradecanoylphorbol-13-acetate (TPA) did not show the growth promoting activities under the same conditions, the action mechanism(s) of exfoliazone and lavanducyanin are different from that of TPA.

Animals↗

Structure-antitumor activity relationship of semi-synthetic spicamycin analogues.

Spicamycin, a nucleoside antibiotic containing fatty acids with a variety of chain lengths (C12-C18), showed potent antitumor activity against human gastric cancer SC-9 and human breast cancer MX-1 in a xenograft model. We have made several semi-synthetic spicamycin analogues (SPMs) which differed in the chain length of the fatty acid moiety, and examined their structure-antitumor activity relationship. The cytotoxic activities of SPMs depended on the chain length of the fatty acid moiety, with dodecanoyl, tetradecanoyl, hexadecanoyl and icosanoyl analogues (SPM VIII, SPM X, SPM XII and SPM XVI) exhibiting the most potent cytotoxic activity against P388 murine leukemia cells. SPM VIII showed the most activity against SC-9 in the human tumor xenograft model with the highest therapeutic index among SPMs. The antitumor activity of SPM VIII was superior to that of mitomycin C.

Animals↗

Quinolidomicins A1, A2 and B1, novel 60-membered macrolide antibiotics. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activity.

Three novel macrolide antibiotics, quinolidomicins A1, A2 and B1, were isolated from the fermentation broth of Micromonospora sp. JY16. Quinolidomicin A1 inhibited the growth of various tumor cells including multidrug-resistant cells. Quinolidomicin B1 was similarly cytotoxic, while quinolidomicin A2 was inactive against these tumor cells.

Animals↗

Tetronothiodin, a novel cholecystokinin type-B receptor antagonist produced by Streptomyces sp. NR0489. III. Structural elucidation.

Tetronothiodin (1) is a potent and selective cholecystokinin type B (CCK-B) receptor antagonist produced by Streptomyces sp. NR0489. Its structure was elucidated to be a macrocyclic compound comprising cyclohexene, alpha-acyltetronic acid and tetrahydrothiophene moieties based on various 2D NMR experiments on 1 and its dihydro derivative. The stereochemistries for the cyclohexene and tetrahydrothiophene rings were elucidated based on the analysis of NOEs obtained by NOESY experiments and NOE difference spectroscopy. The relative configuration of the cyclohexene moiety in 1 was revealed to be the same as that of the corresponding part in kijanimicin and chlorothricin, which can be structurally related to 1 in terms of their containing a cyclohexene ring with a spirotetronic acid in the molecule.

Furans↗

[A case of a giant epidermoid cyst on the occipital scalp].

The authors report a case of a 61-year-old woman presenting with a giant mass on the occipital scalp. The patient had no neurological deficits and was of normal intelligence. The lesion was soft and covered by an unremarkable epidermis. The preoperative radiologic evaluation was made by CT, MR Imaging, and by cerebral angiogram. The mass produced an inhomogeneously low-intensity signal involving also a high-intensity signal. It was shown, on the T1 weighted image, that it did not communicate with the intracranial space, and there was no gadolinium-enhanced lesion. MR Imaging was superior to CT in the evaluation of the giant mass on the scalp and was particularly useful in surgical planning. At surgical resection, a soft fluffy, white-colored tumor which measured 16 x 10 x 7 cm was totally removed. Pathological diagnosis of the tumor was epidermoid cyst.

Epidermal Cyst↗

Nucleotide sequence of a carboxyphosphonoenolpyruvate phosphonomutase gene isolated from a bialaphos-producing organism, Streptomyces hygroscopicus, and its expression in Streptomyces lividans.

The carboxyphosphonoenolpyruvate (CPEP) phosphonomutase gene of bialaphos-producing Streptomyces hygroscopicus, which encodes a C-P bond forming enzyme was cloned into Streptomyces lividans and sequenced. The amino acid composition of the protein coded in an open reading frame of 295 codons and its calculated molecular mass, 32,800 Da, coincided well with those of the purified enzyme. Introduction of the CPEP phosphonomutase gene, the expression of which is controlled by the promoter of the aph gene, into S. lividans resulted in the production of this enzyme at a level almost equivalent to that in the parent strain.

Amino Acid Sequence↗

Purification and characterization of phosphoenolpyruvate phosphomutase from Pseudomonas gladioli B-1.

Phosphoenolpyruvate phosphomutase (PEPPM) catalyzes C-P bond formation by intramolecular rearrangement of phosphoenolpyruvate to phosphonopyruvate (PnPy). We purified PEPPM from a gram-negative bacterium, Pseudomonas gladioli B-1 isolated as a C-P compound producer. The equilibrium of this reaction favors the formation of the phosphate ester by cleaving the C-P bond of PnPy, but the C-P bond-forming reaction is physiologically significant. The C-P bond-forming activity of PEPPM was confirmed with a purified protein. The molecular mass of the native enzyme was estimated to be 263 and 220 kDa by gel filtration and polyacrylamide gel electrophoresis, respectively. A subunit molecular mass of 61 kDa was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that the native protein was a tetramer. The optimum pH and temperature were 7.5 to 8.0 and 40 degrees C, respectively. The Km value for PnPy was 19 +/- 3.5 microM, and the maximum initial velocity of the conversion of PnPy to phosphoenolpyruvate was 200 microM/s/mg. PEPPM was activated by the presence of the divalent metal ion, and the Km values were 3.5 +/- 1.4 microM for Mg2+, 16 +/- 5 nM for Mn2+, 3.0 +/- 1.5 microM for Zn2+, and 1.2 +/- 0.2 microM for Co2+.

Carbon↗

New redistribution index of nutritive blood flow to skeletal muscle during dynamic exercise.

BACKGROUND: Cardiac output is effectively redistributed to working muscle by regional changes in vascular resistance. However, there has been no suitable method to quantify blood flow distribution to large working and nonworking muscles involved in ergometer or treadmill exercise. METHODS AND RESULTS: To quantify the redistribution of blood flow, we compared thallium activity in a bicycle pedaling leg with that in the contralateral resting leg in 10 normal subjects. The regional thallium activity was expressed as a percentage of the whole-body radioisotope activity. Comparison of thallium activity between legs was performed at rest and at the work rates of anaerobic threshold and peak exercise during one-leg exercise. Thallium distribution of both legs was essentially the same at rest. At the anaerobic threshold, thallium activity increased about threefold to fourfold in the exercising thigh and about twofold in the exercising calf. The thallium distribution in these muscles at peak exercise was the same as at the anaerobic threshold. In the nonexercising calf, thallium distribution during exercise decreased significantly, and it was unchanged in the nonexercising thigh. Consequently, the ratio of thallium activity between the exercising and nonexercising thighs increased from 1.1 +/- 0.1 to 4.0 +/- 0.9 at the anaerobic threshold and to 3.3 +/- 0.6 at peak exercise. Similarly, the ratio between the exercising and nonexercising calves increased from 1.0 +/- 0.0 to 3.8 +/- 1.3 at the anaerobic threshold and to 3.5 +/- 1.0 at peak exercise. The ratios at peak exercise, however, did not differ significantly from those at the anaerobic threshold. CONCLUSIONS: These findings suggest that the redistribution of blood flow occurs predominantly during mild to moderate exercise; therefore, blood flow in the leg during strenuous exercise would depend primarily upon an increased cardiac output. Thus, the thallium activity ratio of exercising and nonexercising legs reflects the difference in vascular tone of each leg and could provide a noninvasive and quantitative index of blood flow redistribution.

Adult↗