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Biomedical subjects

N Tamaki

Publications and source records attributed to N Tamaki.

At least 19 recordsLinked to original sources

Inhibition of D-3-aminoisobutyrate-pyruvate aminotransferase by 5-fluorouracil and alpha-fluoro-beta-alanine.

Among pyrimidine derivatives, we found that 5-fluorouracil potently inhibited purified rat liver D-3-aminoisobutyrate-pyruvate aminotransferase, whereas 5-fluorouridine did so to a much lesser extent. 5-Fluorouracil acted as a competitive inhibitor against beta-alanine with a Ki of 56 microM, and was uncompetitive against pyruvic acid, with a Ki of 73 microM. alpha-Fluoro-beta-alanine, a metabolite of 5-fluorouracil, was also a competitive inhibitor with respect to beta-alanine with a Ki of 8.0 mM. 5-Fluorouracil acted also as a competitive inhibitor of 4-aminobutyrate aminotransferase with respect to beta-alanine with a Ki value of 1.9 mM, and was uncompetitive against 2-oxoglutaric acid, with a Ki of 1.8 mM.

Alanine Transaminase

Treatment of early recurrent medulloblastoma in children with cisplatin and etoposide: a preliminary report.

The prognosis of recurrent medulloblastoma remains extremely poor. Combination chemotherapy with cisplatin (CDDP) and etoposide (VP-16) was given to five children with early recurrent medulloblastoma. As a rule, CDDP 20 mg/m2 per day and VP-16 60 mg/m2 per day were administered intravenously for 5 days. This cycle was repeated three times at 4-week intervals. After this therapy, cerebellar signs improved in one case and were unchanged in four cases. Weakness and sensory disturbance, however, improved in three of four patients. Moreover, neck and/or back pain resolved in all these four. Radiological findings improved in three cases. Myelosuppression appeared in all patients, but receded rapidly. No other significant complications were noticed. Two patients died 5 and 6 months after this therapy. These results seem to suggest that this therapy has a use in improving neurological symptoms, particularly neck and/or back pain, although its efficacy is limited.

Adolescent

Histological changes in the midbrain around the aqueduct in congenital hydrocephalic rat LEW/Jms.

Primary aqueductal stenosis is one of the main causes of congenital hydrocephalus in humans and experimental models. The congenitally hydrocephalic rat strain LEW/Jms is one such model. In this report, we describe further detailed histological features of periaqueductal structure, including the posterior commissure, subcommissural organ (SCO), and ependyma, and discuss the changes in these structures in relation to the cause of hydrocephalus. Coronal sections of the aqueduct in normal rats showed that the usual ependyma was absent in the center of the base facing the dorsal side, which was replaced by tall columnar cells. On the other hand, in hydrocephalic rats the ependyma encircled the aqueductal cavity. In midline sagittal sections, normal and hydrocephalic rats showed the SCO, although the SCO in hydrocephalic rats was shorter than in normal rats. There was also a marked difference between normal and hydrocephalic rats in the dorsoventral dimension of the rostral midbrain. In hydrocephalus, this dimension was large in comparison with normal rats. The superior collicular commissure located caudal to the posterior commissure ran along the ventral side of the midbrain in rats with hydrocephalus, and there was a cell-depleted area just dorsal to the superior collicular commissure. The same findings were observed from the 17th day of gestation until the postnatal period. Although the role of the SCO has been widely discussed from the viewpoint of secretory function, the present study indicated that this organ might be involved in the formation of the shape of the aqueduct.

Animals

Myocardial oxidative metabolism in normal subjects in fasting, glucose loading and dobutamine infusion states.

Experimental studies indicated the clearance rate constant of 11C-acetate as an index of regional myocardial oxygen consumption. To assess the response of the clearance rate from the left ventricular (LV) myocardium to the change in plasma substrate levels and to the increase in the cardiac work load in normal subjects, a total of 18 dynamic positron emission tomographic studies were performed at rest in the fasting state (control) (n = 7), after oral glucose administration (n = 4), and during dobutamine infusion (n = 7) in 7 normal volunteers. The clearance rate constant (Kmono) was similar in the control (0.065 +/- 0.017 min-1) and glucose loading states (0.059 +/- 0.008 min-1), whereas a significant increase in Kmono was observed during dobutamine infusion (0.106 +/- 0.018 min-1) (p < 0.01) in relation to the increase in the pressure-rate product with a correlation coefficient of 0.873 (p < 0.01). When the LV myocardium was divided into 6 segments, there were no significant differences among the segments in Kmono values in any condition. These normal responses should be valuable for assessing oxidative metabolic reserve and regional changes in oxidative metabolism in patients with coronary artery disease.

Adult

Clinical evaluation of cardiac function by ambulatory ventricular scintigraphic monitoring (VEST): validation and study of the effects of nitroglycerin and nifedipine in patients with and without coronary artery disease.

Global left ventricular function and ECGs were continuously monitored by radionuclide ambulatory ventricular function monitoring (VEST) and validated against multigated blood pool analysis (MUGA) and left ventriculography in 26 subjects (study 1). Ejection fraction by VEST (Y) showed good correlation with Y = 5.5 +/- 0.79 X (r = 0.91), Y = 1.7 +/- 0.86 X' (r = 0.91), and Y = 11.6 + 0.68 X" (r = 0.82) to sitting and supine MUGA and left ventriculography, respectively. In study 2 left ventricular function and ECGs were evaluated at rest and during exercise without any drug (control), with nitroglycerin, and with nifedipine in 21 patients with coronary disease (group I) and six normal subjects (group II). In group I abnormal ejection fraction responses (exercise increase less than or equal to 6%) during the control exercise period were found in 15 patients (71%), ST segment abnormalities in seven (33%), and chest pain in four (18%). Control exercise increased end-diastolic volume (100 to 112 +/- 8%) and end-systolic volume (53 +/- 15% to 63 +/- 22%) and decreased the ejection fraction (47 +/- 15% to 43 +/- 21%). The ejection fraction during exercise increased after nitroglycerin (50 +/- 22%) or nifedipine (54 +/- 21%) (p less than 0.05). In group II the ejection fraction was unchanged between rest and exercise with or without nitroglycerin or nifedipine. Thus combined radionuclide and ECG monitoring by VEST could detect changes in left ventricular function at rest and during exercise over a prolonged period and demonstrated that nitroglycerin and nifedipine improved cardiac function in the ischemic setting with an increased ejection fraction in the upright position.

Coronary Disease

Anterior choroidal artery syndrome after surgery for internal carotid artery aneurysms.

We report five patients with anterior choroidal artery syndrome after surgery for internal carotid artery aneurysms. All patients suffered hemiparesis, and hemisensory loss and homonymous hemianopsia were identified in 2 patients. The characteristic triad of the syndrome was recognized in only 1 patient. Dominant and nondominant cerebral hemisphere signs have been reported in association with this syndrome, and 2 patients had a speech disturbance in our series. In previous reports, neurological deficits were mild and patient prognosis was good in anterior choroidal artery infarct, in spite of the fact that the artery supplied the corticobulbar and corticospinal tracts. This report suggests the possible causes of this syndrome after surgery for internal carotid aneurysms, which involve vasospasm after subarachnoid hemorrhage, mechanical obstruction, thromboembolism, and distortion of the aneurysm clip.

Adult

Effect of diltiazem on stunned myocardium evaluated with 99mTc-pyrophosphate imaging in canine heart.

The effect of diltiazem on stunned myocardium was evaluated by measuring the myocardial uptake of 99mTc-PYP (pyrophosphate) in open chest experiments with dogs. Myocardial stunning was induced by a 30 min ischemic occlusion of the anterior descending coronary artery. Regional wall motion was monitored by echocardiography of the epicardium for 2 h during reperfusion. After a 30 min occlusion of the coronary artery, it was reperfused and 99mTc-PYP was injected, followed by 201Tl 2 h later. The ischemic area was defined by Evans blue dye, and the infarct area by TTC staining. No dogs showed infarcts or 201Tl defects in this study group. Five dogs of the control-1 group (C1, ischemic area = 19.1 +/- 3.2%) showed decreased regional wall motion during occlusion (15.5 +/- 3.5% of control), and a slow recovery from depressed motion after 2 h of reperfusion (20.3 +/- 9.3%) with uptake ratio (compared to the non-ischemic area uptake) of 99mTc-PYP (4.96 +/- 2.28). In contrast, both groups with diltiazem infusion (20 micrograms/kg/min), started either 30 min before ischemia (D1 = 5 dogs) or just after reperfusion (D2 = 5 dogs), showed significantly better recovery after 2 h of reperfusion (D1:115.4 +/- 36.0%, D2:109.2 +/- 44.2%) than C1 (p less than 0.05), D1 and D2 groups also showed suppressed 99mTc-PYP uptake ratio (D1:1.06 +/- 0.33, D2:2.34 +/- 2.05, p less than 0.05 vs C1) in spite of comparable ischemic area. Four dogs with small ischemic area (C2:5.3 +/- 5.0%) did not show increased 99mTc-PYP uptake (1.15 +/- 0.35), and regional wall motion after 2 h of reperfusion was 96.1 +/- 24.1% of the control value (p less than 0.05 vs C1). Thus, diltiazem was effective in enhancing the suppression of 99mTc-PYP uptake in the stunned myocardium, and similar results were obtained for small ischemic areas. The protective effect of diltiazem appears to be strongly related to the mechanism of 99mTc-PYP uptake.

Animals

Positron emission tomography--usefulness in assessing myocardial viability.

Positron emission tomography (PET) using N-13 ammonia and F-18 fluorodeoxyglucose (FDG) has been used to evaluate myocardial viability in comparison with thallium-201 single photon emission computed tomography (SPECT), and left ventricular wall motion in comparison with contrast ventriculography. Forty patients with anterior myocardial infarction underwent stress and delayed resting perfusion imaging using Tl-201 SPECT and ammonia PET, a glucose metabolism study using FDG PET, and wall motion assessment with left ventriculography. Out of a total of 600 segments of left ventricular imaging, SPECT demonstrated 197 fixed perfusion defects, 99 with redistribution on delayed imaging and 304 normal segments. Of 197 segments with fixed defects, 24 (12%) were normal and 71 (36%) ischemic according to PET criteria. Nineteen of 28 with infarction and all of 12 with non-Q wave infarction showed a viable myocardium. Left ventricular wall motion was significantly better in patients with normal PET findings compared with those with ischemia or scar on PET. Post-PTCA PET revealed improved ammonia PET in 6 of 11 patients but reduced FDG uptake was noted only in 3. These data suggests that Tl-201 SPECT significantly underestimates myocardial viability and that PET imaging is a promising tool for assessing the presence of salvaged myocardium.

Angioplasty, Balloon, Coronary

Chronic subdural hematoma in elderly people: present status on Awaji Island and epidemiological prospect.

The epidemiological aspect of chronic subdural hematoma (CSH) in the elderly who are 65 years old or elder was evaluated on Awaji Island with about 170,000 inhabitants. The overall incidence of CSH was 13.1 per 100,000/year, 3.4 in people under 65 years old, and 58.1 in the elderly. The elderly were 17.7% of all inhabitants. If these incidences of CSH are extrapolated to all of Japan in the year 2020, the incidence will be 16.3 per 100,000/year. This suggests that CSH may become the most common neurosurgical condition.

Adult

Role of dihydropyrimidine dehydrogenase in the uridine nucleotide metabolism in the rat liver.

The activity of dihydropyrimidine dehydrogenase, which is the rate-limiting enzyme in the catabolism of pyrimidine, in livers of 5-day-old rats increased 48 h after glucocorticoid injection. The increase in the activity of dihydropyrimidine dehydrogenase by glucocorticoid administration and by aging did not decrease the uridine, uracil and sigma UMP (the sum of acid-soluble uracil 5'-nucleotides) pool in liver. The increase of liver uracil by a uridine diet not increase dihydropyrimidine dehydrogenase activity. The increase of liver uracil did not increase dihydropyrimidine dehydrogenase activity. However, dihydropyrimidine dehydrogenase activity which increased after glucocorticoid treatment increased the pyrimidine-degradation rate in rat livers and hepatocytes. Pyrimidine catabolism pathway in liver may play an important role in degradation of dietary pyrimidines and pyrimidines which are administered in the form of medicines as 5-fluorouridine.

Age Factors

[Ischemic myocardial injury evaluated using positron emission tomography in children with coronary artery disease: comparison with thallium-201 SPECT].

Regional myocardial perfusion and glucose metabolism were evaluated by positron emission tomography (PET) in children with coronary artery disease. Also, PET findings were compared with those of thallium-201 myocardial single photon computed tomography (SPECT). The study patients consisted of 11 children ranging in age from 3 to 14 years. Ten patients had significantly stenotic coronary arterial lesions due to Kawasaki disease, and one patient had a left coronary artery with an anomalous origin from the pulmonary artery. Evaluation was made before and after surgical revascularization in 3 patients. Regional myocardial perfusion was assessed at rest using 13N-ammonia, and regional myocardial glucose metabolism was assessed at rest under fasting conditions using 18F-fluorodeoxyglucose (18FDG). SPECT was performed after dipyridamole infusion. Initial and delayed images were obtained 7 min and 3 hrs after dipyridamole infusion, respectively. Left ventricular myocardial images were categorized as the septal, anterior, lateral, apical, and inferior segments, and evaluation was made for each segment. A total of 70 myocardial segments in 11 patients were classified into 4 groups according to the PET findings: 1) segments with normal perfusion and without enhanced 18FDG uptake (normal segments; n = 55), 2) normal perfusion with enhanced 18FDG uptake (metabolically abnormal segments; n = 3), 3) hypoperfusion with enhanced 18FDG uptake (ischemic but viable segments; n = 9), and 4) hypoperfusion without enhanced 18FDG uptake (non-viable segments; n = 3). On SPECT, the numbers of myocardial segments showing no perfusion defects, complete redistribution, incomplete redistribution, and persistent perfusion defects were 38, 12, 14, and 6, respectively. Comparisons were made between PET findings and SPECT findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

[A case of hepatocellular carcinoma responding to intraarterial infusion of epirubicin and mitomycin C].

A 64-year-old male was admitted for treatment of hepatocellular carcinoma. He was diagnosed as having many tumors in the area of S6 and the AFP level was elevated to 878 ng/ml. Initially, intraarterial infusion of Epirubicin only was not effective. After the first course of treatment, tumors increased in size and the AFP level was elevated. Next, intraarterial infusion of Epirubicin and Mitomycin C was performed. After the second course of treatment, the AFP level decreased from 5,006 ng/ml to 754 ng/ml and the tumors had almost completely disappeared on angiography. The tumors continued to decrease in size and thereafter the AFP level decreased to 10 ng/ml and was not elevated. The tumors almost completely disappeared in this case, and the coadministration of Epirubicin and Mitomycin C provided effective.

Antineoplastic Combined Chemotherapy Protocols

Viable myocardium identified by reinjection thallium-201 imaging: comparison with regional wall motion and metabolic activity on FDG-PET.

Reinjection thallium-201 scans were performed in 68 patients with coronary artery disease after the routine stress-delayed scans for more accurate identification of new fill-in. Following the stress and 3 hour delayed thallium-201 SPECT scans, 40 MBq (1.1 mCi) was injected at rest, and 10 min later, the reinjection SPECT scan was obtained. To determine whether the reinjection method can aid in identifying ischemic but viable myocardium, the thallium-201 findings were compared with regional wall motion on radionuclide ventriculography in 61 patients and with metabolic activity on positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) in 18 patients. The reinjection scan identified new fill-in which had not been shown on the stress-delayed scans in 6 of the 22 patients (27%) or in 29 of the 105 segments (28%). Regional wall motion was preserved more in the segments that exhibited new fill-in after reinjection (wall motion score = 1.64 +/- 1.29) than in those without new fill-in (score = 2.72 +/- 1.04) (p < 0.01). In the comparative study with FDG-PET, persistent FDG uptake was observed in all segments with new fill-in (20/20 segments: 100%); whereas, it was seen in only 7 of the 28 segments (25%) without new fill-in after reinjection (p < 0.05). We concluded that the segments having new fill-in after reinjection may represent ischemic but viable myocardium. Thus, the reinjection thallium-201 scan should be performed to identify ischemic myocardium which occasionally cannot be detected by the routine stress-delayed thallium-201 scans.

Adult

[Evaluation of the sensitized condition of patients with allergic diseases in Okinawa using the MAST allergy system].

We determined, using the MAST system, specific IgE antibodies to allergens in the circulating blood of 127 patients with bronchial asthma, allergic rhinitis and atopic dermatitis in Okinawa. The positive rates to inhalant allergens in all patients examined by the MAST system were as follows: Dermatophagoides farinae 65%, house dust 58%, cat epithelium 17% and Japanese cedar 9%. In addition, the positive rates to food allergens found in all patients were as follows: wheat 16%, shrimp 14%, egg white, rice and crab 12%. The average number of positive allergens in the patients with atopic dermatitis was larger than that in those with allergic respiratory diseases only. The above five specific IgE antibodies were detected simultaneously in 12 (9%) of the 127 patients. In addition, the average number of overlapping positive allergens was 2.0 in all patients. From these results, it was suggested that the number of overlapping positive allergens in patients on Okinawa is smaller than in other areas of Japan as compared with other papers.

Adolescent

Crossed cerebellar hypoperfusion in unilateral major cerebral artery occlusive disorders.

We evaluated regional blood flow and oxygen metabolism in the cerebral and cerebellar cortices of 15 patients with unilateral major cerebral artery occlusive disorders with PET. These patients showed a cortical blood flow asymmetry in middle cerebral artery distribution. Only subcortical abnormalities were detected on computed tomography. Nine patients showed crossed cerebellar hypoperfusion, a reduction in contralateral cerebellar blood flow, while six did not. No difference in the degree of cerebral blood flow asymmetry existed between the two patient groups. However, oxygen metabolism asymmetry was more pronounced and was more closely matched to blood flow asymmetry in patients with crossed cerebellar hypoperfusion. These findings suggest that a major cause of cerebral cortical blood flow reduction is reduced metabolic demand in patients with crossed cerebellar hypoperfusion. Crossed cerebellar hypoperfusion may have clinical significance as a reflection of the cerebral metabolic state on blood flow images.

Adult

Regional metabolic abnormality in relation to perfusion and wall motion in patients with myocardial infarction: assessment with emission tomography using an iodinated branched fatty acid analog.

The clinical usefulness of single-photon tomography using both a beta-methyl-branched fatty acid analog, 123I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) and 201TI was assessed in 4 normal subjects and 28 patients with myocardial infarction. A homogeneous distribution of the tracer in the left ventricular myocardium was observed in each normal subject. BMIPP uptake was decreased compared to 201TI (discordant) in 17/28 patients (61%) and in 49/196 myocardial segments (25%). Such discordant BMIPP uptake was observed more often in areas of acute myocardial infarction (59% at less than or equal to 4 wk versus 31% at greater than 4 wk after onset) (p less than 0.01) and areas supplied with revascularized arteries (74% for revascularized versus 28% for nonrevascularized areas) (p less than 0.01). In addition, the discordant BMIPP uptake was seen more often in the segments exhibiting a wall motion score lower than the perfusion score (46%) in comparison to segments showing a similar decrease in both the wall motion and perfusion scores (12%) (p less than 0.01). Thus, BMIPP imaging may play a major role in increasing our understanding of the relationship between perfusion and wall motion, particularly in patients with acute myocardial infarction and those who received revascularization therapy.

Fatty Acids

[Phase 2 study of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid, a myocardial imaging agent for evaluating myocardial fatty acid metabolism].

A phase 2 study of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid (123I-BMIPP), a myocardial imaging agent developed for evaluating myocardial fatty acid metabolism, was performed in 197 patients with various heart diseases. The myocardial distribution of 123I-BMIPP did not change from early to late images in 88% of 91 patients with ischemic heart disease (IHD), while washout and/or fill-in were observed in 45% of 55 patients with hypertrophic cardiomyopathy (HCM). In comparison with 201Tl in 165 patients with various heart diseases, the decrease in uptake was more profound with BMIPP in 56% and with 201Tl in only 4%. 123I-BMIPP showed more severely decreased uptake in 83% of the patients with subacute myocardial infarction (15 to 30 days after the onset) and in 73% of the patients with HCM. High-quality SPECT images were obtained with 123I-BMIPP in 93% of 194 patients analyzed. However, the image quality in cardiomyopathy was inferior to that in IHD. The optimal injection dose range and standard dose of 123I-BMIPP were considered to be 74-148 MBq and 111 MBq, respectively. These findings suggest that 123I-BMIPP myocardial imaging is safe and useful for evaluating myocardial fatty acid metabolism in various heart diseases.

Adolescent

[Acute lymphocytic leukemia (L1) preceded by hypercalcemia].

A 37-year-old female with hypercalcemia presented with lumbago, nausea and vomiting. Peripheral blood (PB) and bone marrow (BM) smears revealed no lymphoblasts on the first admission. The value of parathyroid hormone related protein (PTHrP) was increased and osteoporosis was found in the lumbar vertebrae. After 5 months, diagnosis of acute lymphocytic leukemia (ALL) was made on the evidence that lymphoblasts were found in PB (1%) and in BM (98%). Treatment with vincristine, daunorubicin, prednisolone and L-asparaginase achieved complete remission (CR) and the serum calcium level returned to the normal range. She has maintained CR, and is currently treated with consolidation therapy by cyclophosphamide and methotrexate. Acute leukemia is known to be rarely accompanied with hypercalcemia. This rare case was accompanied with hypercalcemia in acute leukemia. Hypercalcemia appeared to be attributable to the increased bone absorption by PTHrP derived from tumor cells. This important case will help understanding the etiology of hypercalcemia associated with ALL.

Adult