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Biomedical subjects

H Seto

Publications and source records attributed to H Seto.

At least 163 records · Page 9Linked to original sources

Whole-body 201Tl scintigraphy during one-leg exercise and at rest in normal subjects: estimation of regional blood flow changes.

To determine the effect of exercise intensity on regional blood flow in exercising and resting leg muscles and organs, we assessed relative changes in the regional distribution of 201Tl during one-leg ergometer exercise and at rest by whole-body scintigraphy as an estimate of regional blood flow changes in 10 healthy males. The regional 201Tl activity was expressed as a percentage of the whole-body activity, and relative changes in each region were compared to those at the anaerobic threshold (AT) and at peak exercise. In the legs, the distribution of 201Tl in the exercising thigh and calf increased significantly at the AT to 390.7 and 219.2% respectively of resting levels (both P < 0.01), but remained unchanged the resting thigh from rest to peak exercise. Conversely its distribution in the resting calf decreased significantly at the AT to 60.0% of the resting level (P < 0.01). However, there were no significant differences between AT and peak exercise. In the organs, the distribution of 201Tl in the lung, liver, spleen and kidneys decreased significantly at the AT to 88.4 +/- 10.4%, 67.0 +/- 11.5%, 62.4 +/- 11.8% and 67.0 +/- 8.6% respectively of resting levels (all P < 0.01). Redistribution of blood flow to the exercising leg occurs predominantly during mild to moderate exercise. Therefore, blood flow in the leg during strenuous exercise depends primarily upon an increase in cardiac output. The splanchnic organs are the major sources of redistribution.

Adult↗

Promoinducin, a novel thiopeptide produced by Streptomyces sp. SF2741.

Our continued screening to find tipA promoter-inducing substances resulted in the isolation of promoinducin from a mycelial extract of Streptomyces sp. SF2741. Based on various 1D- and 2D-NMR studies, including field gradient (FG)-COSY, HSQC, FG-HMBC, phase-sensitive 13C-decoupled HMBC and NOESY experiments, promoinducin's structure was established to be a thiopeptide composed of threonine, some unusual amino acids masked at their carboxyl groups by thiazole or methyloxazole rings, sulfomycinamate and five dehydroalanine residues. Promoinducin induced the tipA promoter at 40 ng/ml, and also exhibited strong antibacterial activity against some Gram-positive bacteria.

Amino Acid Sequence↗

Trachyspic acid, a new metabolite produced by Talaromyces trachyspermus, that inhibits tumor cell heparanase: taxonomy of the producing strain, fermentation, isolation, structural elucidation, and biological activity.

Trachyspic acid, a new metabolite that inhibited heparanase, was isolated from the culture broth of Talaromyces trachyspermus SANK 12191. Its structure was deduced from NMR spectral analyses and chemical reactions as a tricarboxylic acid derivative containing a spiroketal. The IC50 value of trachyspic acid against heparanase was 36 microM.

Ascomycota↗

Anguinomycins C and D, new antitumor antibiotics with selective cytotoxicity against transformed cells.

The retinoblastoma protein (pRB) is inactivated during the development of a wide variety of human cancers. In the course of our screening for antitumor antibiotics by using pRB-inactivated cells, an actinomycete strain was found to produce two active substances, which were elucidated to be new members of the leptomycin-anguinomycin family by NMR spectral analysis and were designated anguinomycins C and D. The anguinomycins induced growth arrest against normal cells and induced cell death against transformed cells, in which pRB was inactivated by viral oncoproteins such as human papillomavirus E7, adenovirus E1A and simian virus 40 large T antigen.

Animals↗

[Assessment of tumor viability by 201Tl SPECT in VX-2 tumor-bearing rabbits after irradiation: comparison with X-ray CT and pathohistologic findings].

In order to evaluate 201Tl SPECT for the assessment of tumor viability after radiation therapy. Twenty rabbits were implanted with VX-2 tumor in the left femoral muscles and were classified into four groups as follows: normal control group (N), 20 Gy irradiated response group (A), 20 Gy irradiated non-response group (B), and 40 Gy irradiated group (C). Eight days after implantation, 201Tl SPECT and CT studies were performed to assess the changes in 201Tl uptake and tumor volume at 0, 1, 2, 3, and 4 weeks after single irradiation. Histologic specimens were also taken. In group N tumors continued to increase in volume, but 201Tl uptake showed a steady decrease after 2 weeks. In group A tumors continued to increase in volume, but 201Tl uptake showed a transient decrease at 2 weeks, then a steady increase. In group B tumors showed a transient increase in volume at 2 weeks, then a continuous decrease, but 201Tl uptake showed a continuous decrease throughout the study. In group C there was a continuous decrease both in volume and 201Tl uptake with the later more prominent. 201Tl uptake was decreased earlier than tumor volume both in group B and C, at one week that was significant (p < 0.01). 201Tl uptake by tumor reflects the burden of viable tumor on histology; therefore 201Tl SPECT is of great use in assessing the therapeutic effects on tumors.

Animals↗

Neurotoxicity and pharmacokinetics of ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) in dogs.

Ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), a water soluble nitrosourea with log P -0.71, may be efficacious in the treatment of subarachnoid dissemination of malignant glioma. We used 2 dogs to study the neurotoxicity and pharmacokinetics of MCNU. MCNU (1 mg), dissolved in 10 ml of artificial CSF, was administered via the right lateral ventricle during a period of 18 to 42 min and the CSF was drained by lumbar puncture. The perfusion was repeated once a week for 10 consecutive weeks. No neurological and systemic symptoms were noted after perfusion. Histological examination of the brain and spinal cord showed local denudation of the ependyma and local subependymal spongy degeneration and gliosis in the lateral ventricle into which MCNU was administered in one dog and local denudation of the ependyma in the other. When administration was over a period of 21 to 38 min, the MCNU concentration in the lumbar CSF peaked at 11.11 to 50.67 micrograms/ml, in 28 to 78 min. The area under the drug concentration-time curve (AUC) was 1152 micrograms x min/ml on average, significantly larger than that of ACNU. The elimination phase followed linear kinetics and the half-time was 41.1 min on average, significantly longer than that of ACNU. These findings suggest that ventriculolumbar perfusion of MCNU may be effective in the treatment of subarachnoid dissemination of malignant glioma notwithstanding some local histological changes.

Animals↗

Expression of PDGF, PDGF-receptor, EGF-receptor and sex hormone receptors on meningioma.

The expression of platelet derived growth factors (PDGF), the PDGF-Receptor (R) (alpha and beta types), epidermal growth factor (EGF)-Receptor (R) and sex hormone (oestrogen and progesterone) receptors was studied in 22 meningiomas. All tumours were PDGF-R beta type positive and 21 (95%) were PDGF positive. Only 2 (9%) were PDGF-R alpha type positive, 13 (59%) were EGF-R positive. The expression of these proteins was not related to the histological type or the malignancy of the meningiomas although the expression of PDGF and PDGF-R beta tended to be stronger in malignant meningiomas. Oestrogen and progesterone receptor protein were examined in 19 patients (10 females and 9 males). None of the meningioma cells revealed oestrogen receptor protein while 17 (89%) of the 19 meningiomas were positive for progesterone receptor protein. The expression of progesterone receptor was not related to histological type or malignancy. Our studies suggest that the autocrine system, through PDGF and PDGF-R type beta, may play an important role in the tumourigenicity of meningiomas. EGF-R was present in almost half and progesterone receptor in most of the meningiomas. There was no correlation between the expression of either PDGF, PDGF-R or EGF-R and the expression of progesterone receptor protein.

Adult↗

Bone marrow scintigraphy in the diagnosis of bone metastasis in prostate cancer.

We investigated bone marrow scintigraphy in 20 patients with prostate cancer to determine the usefulness of this procedure in the diagnosis of bone metastasis. Thirteen of 17 patients whose bone scans revealed hot spots showed accumulation defects in bone marrow scintigrams. Follow-up study and X-ray, computed tomography and/or magnetic resonance imaging findings confirmed the presence of bone metastases in these patients. On the other hand, 4 patients with abnormal bone scans had normal bone marrow scintigrams, and were subsequently demonstrated to have degenerative changes of the spine. Bone marrow scanning therefore appears to be useful in distinguishing metastatic lesions from degenerative changes in cases with suspected bone lesions.

Aged↗

Diffuse increased renal uptake on bone scintigraphy in acute tubular necrosis.

Acute renal failure after exercise with frank pain and patchy renal vasoconstriction is a clinical syndrome that occurs in young, previously healthy persons. The authors describe a 24-year-old man who had this syndrome. CT scan showed wedge-shaped contrast enhancement of both kidneys, which suggested patchy renal vasoconstriction. Tc-99m MDP imaging revealed diffuse increased uptake of both kidneys. After renal function was improved, Tc-99m MDP imaging showed normal uptake of both kidneys. Acute renal failure due to acute tubular necrosis was confirmed by renal biopsy. The authors conclude that Tc-99m MDP may be useful in evaluation of acute renal failure after exercise with flank pain and patchy renal vasoconstriction due to acute tubular necrosis.

Adult↗

Importance of total leg muscle mass for exercise intolerance in chronic heart failure.

Patients with chronic heart failure symptoms tend to avoid voluntary effort and are thus subject to physical deconditioning. The presence of symptoms in daily life is thought to predispose to physical deconditioning and subsequent skeletal muscle loss. This study was designed to describe the relation among daily physical activities, skeletal muscle loss and exercise capacity in patients with chronic heart failure. We studied 14 patients with severe cardiac dysfunction (left ventricular ejection fraction < 40%) and 7 age-matched normal subjects. We measured total leg muscle mass by dual energy X-ray absorptiometry. The patients were divided into 7 asymptomatic and 7 symptomatic individuals using questionnaires for specific physical activities. Peak oxygen uptake and anaerobic threshold were significantly reduced in cardiac patients as compared with normal subjects. The reduction in exercise capacity was greater in the symptomatic patients than in asymptomatic patients. Leg muscle mass was significantly reduced (-17%) in the symptomatic patients, while it remained normal in the asymptomatic patients. Oxygen uptake in unit muscle mass at the level of anaerobic threshold and at peak exercise was decreased in both the asymptomatic (-21% and -21%, respectively) and symptomatic patients (-27% and -30%, respectively) but the difference between these two groups was not significant. In the asymptomatic patients, the reduced exercise capacity was accounted for primarily by muscle mass-independent factors such as an impaired nutritive blood flow to exercising muscles or metabolic abnormalities within the muscle cell. In the symptomatic patients, the marked reduction in exercise tolerance was attributable to a decrease in leg muscle mass and to hemodynamic or metabolic abnormalities. We conclude that the loss of leg muscle mass plays an important role in exercise intolerance in patients who are prone to physical deconditioning as a result of symptomatic heart failure.

Absorptiometry, Photon↗