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Biomedical subjects

H Seto

Publications and source records attributed to H Seto.

At least 181 records · Page 10Linked to original sources

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↗

Cororubicin, a new anthracycline antibiotic generating active oxygen in tumor cells.

In the course of our screening for antitumor antibiotics which show biological activities by generating active oxygen in tumor cells. Micromonospora sp. JY16 was found to produce a new anthracycline antibiotic designated cororubicin. The structure of cororubicin was elucidated as shown in Fig. 5 on the basis of NMR spectral analysis. Cororubicin generated superoxide radicals in tumor cells and showed cytotoxicity, which was reduced by addition of an antioxidative agent, dithiothreitol (DTT).

Anthracyclines↗

Antitumor activity of SPM VIII, a derivative of the nucleoside antibiotic spicamycin, against human tumor xenografts.

The antitumor activity of spicamycin analogue SPM VIII against human stomach, breast, lung, colon and esophageal cancers was compared to that of mitomycin C (MMC) in the human tumor-nude mice xenograft model. Comparative studies of SPM VIII given i.v. at 6 mg/kg/day daily for 5 days and MMC given i.v. at 6.7 mg/kg on day 1 revealed that the antitumor spectrum of SPM VIII showed a different pattern from that of MMC and that SPM VIII caused tumor mass reductions in more tumors than did MMC in colon cancers (4/12 versus 1/11). In addition to this study, a comparative study of SPM VIII given i.v. at 12 mg/kg/day 8 times at 3- or 4-day intervals and 5'-deoxy-5-fluorouridine (5'-DFUR) given po at 185 mg/kg/day 5 days per week for 4 weeks showed that SPM VIII had the highest effect on SC-9 human stomach cancer and COL-1 human colon cancer among the 3 compounds, resulting in a significant reduction of tumor mass. Although other pharmacological studies are in progress, these results suggest that SPM VIII might be a novel antitumor compound effective for human cancers including cancer of the digestive organs.

Animals↗

Hispidospermidin, a novel phospholipase C inhibitor produced by Chaetosphaeronema hispidulum (Cda) Moesz NR 7127. II. Isolation, characterization and structural elucidation.

Hispidospermidin (1) is a novel phospholipase C inhibitor produced by Chaetosphaeronema hispidulum (Cda) Moesz NR 7127. Its structure (C25H47N3O) has been elucidated as a cage compound with a trimethylspermidine side chain based on various NMR studies, including 1H-1H COSY, 13C-1H COSY, HOHAHA, HMBC, COLOC and long range J C-H resolved 2D spectroscopy. The absolute configuration of 1 has been elucidated by modified Mosher's method on the (R)- and (S)-MTPA amides of a derivative of 1.

Chaetomium↗

Assessment of residual tumor viability in thymic carcinoma by sequential thallium-201 SPECT: comparison with CT and biopsy findings.

We present a case of 201TI accumulating thymic carcinoma, in which sequential CT scans demonstrated a steady decrease in tumor volume. The presence of a residual mass on CT scans after the completion of therapy presented the clinical dilemma of whether or not a viable tumor remained. Sequential 201TI SPECT images demonstrated a marked decrease in tumor uptake. At 2 wk after therapy, no significant accumulation of 201TI in the region of the residual mass was observed, indicating a lack of viable tumor. A biopsy specimen revealed no tumor cells. Sequential histopathologic findings were correlated well with the findings of 201TI SPECT rather than those of CT. Thallium-201 SPECT is of great clinical value in assessing tumor viability in the course of therapy.

Aged↗

Basilar artery migraine. Reversible ischemia demonstrated by Tc-99m HMPAO brain SPECT.

The authors present a case of basilar artery migraine in a 33-year-old woman who was initially misdiagnosed as having a cerebrovascular or mental disorder and subjected to MRI and cerebral angiography, which, however, did not show any pathologic findings. During admission to the university hospital, she lost consciousness. An emergency Tc-99m HMPAO brain SPECT showed a significant decrease of regional cerebral blood flow in the right temporal and occipital cortices, and right cerebellar hemisphere, where regional cerebral blood flow was decreased by 10-24% as compared to the left side. The second brain SPECT during a symptom-free phase showed the reversion of regional cerebral blood flow to normal in these areas. Basilar artery migraine was diagnosed by the finding of reversible ischemia in the territory of the right basilar artery on brain SPECT images and the clinical picture.

Adult↗

[MR evaluation of common femoral arterial flow: age-related changes and characteristics in obstructive arterial disease of lower extremities].

Flow velocity measurements of the common femoral arteries in 60 lower extremities of 30 healthy subjects and 12 lower extremities of 7 patients with arteriosclerosis obliterans (ASO) were performed by means of magnetic resonance imaging with a use of presaturation bolus tracking (PBT) method. Our PBT method can provide both precise determination of flow velocity and evaluation of flow patterns within 30 minutes in the clinical setting. In phantom study, MR flow velocity had good correlation with actual flow velocity (r = 0.997). 30 healthy volunteers were classified into three groups; group I (20-40 years), group II (41-60 years) and group III (61-80 years). Starting time of acceleration (STA) were shortened as the age progressed. Peak reverse velocity (PRV), maximum deceleration rate (MDR), peak forward velocity/mean velocity ratio (PFV/MV) and pulsatility index (PI) were significantly decreased in group III as compared to group I and group II. Although intraluminal flow profile showed almost uniform during acceleration time on MR images, flow profile became disproportioned and reverse flow was observed in the medial portion during deceleration time. These characteristic hemodynamics were recognized in all healthy subjects regardless to the different age group. In ASO, STA was prolonged and PFV, PRV, Maximum acceleration rate, MDR, PFV/MV, PI, Vascular sectional area, flow volume were significantly decreased (p < 0.001) as compared to the control healthy group III. As the result we obtained marked characteristics such as flattening of curves and disappearance of reverse flow in MR flow waveform. On MR images, disproportion of intraluminal flow profile, decreased flow velocities during acceleration time and disappearance of reverse flow (11 of 12 extremities) during deceleration time were observed.

Adult↗

Long-term efficacy of heparin exercise treatment for patients with chronic effort angina: evaluation by exercise Tl-201 myocardial scintigraphy.

To determine the effects of heparin exercise treatment on the coronary collateral flow reserve, exercise thallium-201 myocardial perfusion images were obtained with the same work-load before and late after heparin exercise treatment (17 +/- 2 months, mean +/- S.E.). In six patients with stable effort angina, to develop the collateral circulation, treadmill exercise was performed 20 times for 2-3 weeks with pretreatment with a single intravenous dose of heparin (5000 IU). The coronary collateral flow reserve was measured quantitatively as a severity score by analysis of exercise thallium-201 myocardial perfusion images. The severity score was decreased from 11,976 +/- 1722 to 5531 +/- 1967 (P < 0.05) long after heparin exercise treatment. The ST segment depression at the time of peak exercise was also decreased from 0.15 +/- 0.02 mV to 0.05 +/- 0.02 mV. In an additional five medically treated patients, these indexes remained unchanged during 18 +/- 3 months of follow-up period. These findings demonstrate that the coronary collateral flow reserve is significantly enhanced with heparin exercise treatment. These preliminary results lend support for heparin exercise treatment as one of the possible therapeutic modalities for treating patients with chronic stable effort angina.

Aged↗

Determination of polycyclic aromatic hydrocarbons in the lung.

Polycyclic aromatic hydrocarbons (PAHs) accumulated in human lung samples from men (n = 236) and women (n = 128) were determined by high-performance liquid chromatography (HPLC) to examine their association with lung cancer. The mean values for benzo[a]pyrene (BaP), benzo[k]fluoranthene (BkF), and benzo[g,h,i]perylene (BghiP) in lungs (ng/g dry lung) of Japanese autopsied patients were 0.54, 0.44, and 0.87, respectively. The modal values were 0.3, 0.3 and 0.5, respectively. Each of the PAH concentrations was highly correlated with the others (r > 0.83). PAH concentrations in the lungs showed age-related increases with low correlation-coefficient values. BaP, BkF and BghiP concentrations in lungs of various subgroups were in the following order: male > female; and lung cancer > all cancers > non-cancer among male not female group. Only BghiP concentration in the lungs of the male smoker group is significantly higher (P < 0.10) than that of the male non-smoker group. Even among non-smoker groups, PAH concentrations in the lungs of male group were significantly higher than those of female group. In the male population, excess exposure to PAHs together with fine carbon particles, such as tobacco smoke or diesel exhaust, correlated with increased prevalence of lung cancer.

Adult↗

Colloid liver SPECT of hepatic alveolar echinococcosis.

Seventy-one-year-old man had a liver mass. He lived in Hokkaido, where there is an epidemic of hydatic disease. Abdominal US image showed an echogenic mass. CT revealed a low density mass with an unclear margin. A 99mTc-Sulfur colloid liver SPECT study was performed to detect the liver mass. The SPECT scan was done after intravenous administration of 5 mCi of 99mTc-sulfur colloid, and it revealed a lack of uptake in the liver mass. The liver SPECT findings were correlated with subsequent CT and US imaging. Echo-guided biopsy showed a PAS-positive cuticle layer of echinococcosis in the necrotic tissue. This is the first report of a case of detection of hepatic alveolar echinococcosis by means of a colloid liver SPECT imaging procedure.

Aged↗