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Biomedical subjects

K Sakata

Publications and source records attributed to K Sakata.

At least 307 records · Page 17Linked to original sources

Analysis of the results of combined therapy for maxillary carcinoma.

BACKGROUND: Maxillary sinus carcinomas usually are locally advanced. A wide variety of modalities, including surgery, radiation therapy, and intraarterial chemotherapy, alone or in combination, have been used. However, there is still much controversy with regard to the optimum treatment. METHODS: From 1972 to 1986, 108 patients with squamous cell carcinoma of the maxillary sinus were treated at the Department of Radiology, University of Tokyo Hospital. From 1972 to 1974 (the first period), the treatment consisted of operation for reduction of tumor volume, daily cleaning of the maxillary antrum, 20 Gy of postoperative radiation therapy, and intraarterial infusion of 1500 mg of 5-fluorouracil (5-FU) and 3000 mg of 5-bromodeoxyuridine (BUdR). From 1975 to 1979 (the second period), the radiation dose was reduced to 10 Gy, and intraarterial infusion of 5-FU and BUdR was not performed. Surgery for reduction of tumor volume and daily cleaning of the antrum played a major role in this period. From 1980 to 1982 (the third period), daily cleaning of the antrum was not performed. Instead, the dose of radiation was increased to 50-60 Gy. From 1983 to 1986 (the fourth period), more extensive surgery to resect the tumor en bloc was introduced. The radiation dose was increased to 70 Gy. Intraarterial infusion of 3750 mg of 5-FU and 120 mg of cisplatin also was administered. RESULTS: The 5-year survival rate was 46% in the first period, 24% in the second period, 7.2% in the third period, and 53% in the fourth period. In the third period, there were more cases in which death resulted from a cause other than local failure, such as distant metastasis, pneumonia, or secondary primary cancer. Since 1984, we planned treatment with computed tomography (CT) and used the linear accelerator with a multileaf collimator to treat patients with an irregular field of irradiation. These have made it possible to administer radiation therapy in doses as high as 70 Gy without severe complications and improve the survival rate, especially for T4 disease. CONCLUSIONS: Radiation plays an important role in sterilizing malignant cells that cannot be removed by operation. The dose of radiation should be determined according to the volume of residual tumor. Careful treatment planning is required to irradiate the tumor adequately and reduce complications.

Antineoplastic Combined Chemotherapy Protocols↗

ETB receptor antagonist, IRL 1038, selectively inhibits the endothelin-induced endothelium-dependent vascular relaxation.

In isolated rat aorta, endothelin-1 induced contractions at lower concentrations than endothelin-3. The contractile effects were augmented by removing the endothelium. In contrast, endothelium-1 and endothelin-3 at similar concentrations induced endothelium-dependent relaxation in norepinephrine-stimulated aorta. IRL 1038 ([Cys11,Cys15]endothelin-1(11-21); 3 microM) augmented the contractile effects of endothelins only in the presence of the endothelium. IRL 1038 (0.3-3 microM) inhibited the endothelium-dependent relaxation induced by endothelins but not by carbachol. IRL 1038 itself did not change muscle tension. These results suggest that IRL 1038 is a novel antagonist of the ETB receptor responsible for the release of relaxing factor from the vascular endothelium.

Animals↗

Transformation of coronary artery aneurysm to obstructive lesion and the role of collateral vessels in myocardial perfusion in patients with Kawasaki disease.

OBJECTIVES: The aim of this study was to examine the transformation of coronary artery aneurysms to obstructive lesions and to assess the role of collateral vessels in patients with Kawasaki disease. BACKGROUND: Coronary artery aneurysms, especially giant aneurysms, are known to become obstructive lesions in patients with Kawasaki disease. However, the process of transformation is not yet clear. METHODS: Thirty patients (average age 9.9 years) with obstructive lesions secondary to Kawasaki disease underwent repeated coronary artery angiography and thallium myocardial scintigraphy over a mean period of 7.7 years after the acute onset of Kawasaki disease. RESULTS: In the 27 patients who were enrolled in the acute phase of the disease because of coronary artery aneurysms, the later transformation to obstructive lesions was not significantly different between the 61 large and 6 medium-sized aneurysms. Obstructive transformation of aneurysms was more rapid in the right than in the left coronary artery (p < 0.001). From the last coronary angiogram obtained, the obstructive lesions were classified as localized stenosis > 90% in 10 vessels, occlusions in 6 vessels and segmental stenosis in 26 vessels. Both localized and segmental stenosis occurred significantly more often in the left anterior descending and the right coronary artery than in other vessels (p < 0.05). The incidence of collateral vessels was significantly correlated with a younger age at onset of Kawasaki disease, especially in patients with segmental stenosis (p < 0.001). Collateral vessels did not develop in the presence of localized stenosis regardless of the occurrence of myocardial ischemia. All occluded vessels had collateral development regardless of the presence of myocardial infarction. CONCLUSIONS: The treatment of localized stenosis may play an important role in preventing myocardial infarction in the chronic phase of Kawasaki disease.

Acute Disease↗

Distinction between the depletion of opsonins and the saturation of uptake in the dose-dependent hepatic uptake of liposomes.

Opsonins play a role in the hepatic uptake of particles such as bacteria, lipid emulsion, and liposomes. The objective of this study was to distinguish between opsonin depletion and uptake saturation in the dose-dependent hepatic uptake of liposomes. The uptake of opsonized and unopsonized liposomes was determined in the isolated perfused liver. Serum (2.9 mL) was required to opsonize 1 mumol liposomes fully, indicating that a rat (250 g with 10 mL of serum) can opsonize 3.5 mumol liposomes. Next the dose effect on hepatic uptake of opsonized and unopsonized liposomes was examined. Saturation of uptake was found only for the opsonized liposomes. On the other hand, the hepatic uptake clearance decreased dose dependently from 4.31 to 0.79 (mL/min), with increasing doses from 0.075 to 17 mumol/250 g, respectively, after i.v. administration. Thus, the decrease in the hepatic uptake clearance at the medium dose was due to the saturation of uptake alone, and at the high dose it was due to opsonin depletion as well. These results show that the saturation of liposomal uptake in the liver and the depletion of opsonins occurred at different liposome dosage levels.

Animals↗

Improved growth and taxol yield in developing calli of Taxus cuspidata by medium composition modification.

Cell culture of Taxus spp. represents a potential alternative source of taxol and related taxanes used in cancer chemotherapy. We have analyzed the effect of different culture media components on growth and production of taxol in developing callus cultures of T. cuspidata. Several sequential modifications were made to the basal B5 medium, which included addition and/or variation in the concentration of sucrose, B5 organic supplements, gibberellic acid, 36 combinations of 2,4-D/kinetin ratios, media salts and organic supplements, phenylalanine, casein hydrolysate and medium pH. The experiments were conducted during a 55 day-growth period followed by taxane extraction and analysis. Significant increases in taxol yield and growth over basal medium grown calli were observed with some of the modified media.

2,4-Dichlorophenoxyacetic Acid↗

Metabolic interaction of ethanol and cyclohexanone in rabbits.

The interaction of ethanol (EtOH) and cyclohexanone (CHN) metabolism was studied to demonstrate the influence of alcohol beverage in cyclohexanone poisoning. Rabbits were administered CHN and EtOH separately or together, and the plasma concentration of CHN and cyclohexanol (CHL), a metabolite of CHN, and blood concentrations of EtOH were measured at various times. When CHN alone was administered orally, the time to maximum plasma concentration (Tmax) of CHN was as short as 15 min, but that of CHL was 120 min. The short Tmax of CHN was considered to be due to the first-pass effect. The plasma concentration of CHL was much greater than that of CHN. On the other hand, when the same amount of molar CHL was administered in rabbits for sake of comparison, only small amounts of CHN were detected in plasma. The interconversion between CHN and CHL at the time of equilibration tended to shift predominantly toward the formation of CHL, whose plasma concentration ratio was about 1:6 to 1:8. The coadministration of EtOH decreased the plasma concentration of CHN and increased that of CHL more than the administration of CHN alone. The blood concentration of EtOH was also decreased with the coadministration of CHN. The coadministration of EtOH with CHN demonstrated an acceleration in the metabolism of both CHN and EtOH, which may be due to an increase in the concentrations of the alcohol dehydrogenase-NADH and -NAD complexes.

Administration, Oral↗

Erythromycin inhibits the production of elastase by Pseudomonas aeruginosa without affecting its proliferation in vitro.

Extracellular proteases from Pseudomonas aeruginosa play important roles in infections in the respiratory tract. The effect of erythromycin (EM), a macrolide antibiotic, on the production of elastase by P. aeruginosa was investigated in vitro and compared with the effect of other antibiotics. Thirty-four (94.4%) of thirty-six different strains produced detectable amounts of elastase determined by the gel diffusion method. The elastase production was inhibited completely by EM in 27 (79.4%) of 34 strains at some concentrations between 0.125 and 64 micrograms/ml. At 4 micrograms/ml or less, the elastase production was inhibited completely in four (11.8%) strains and more than 50% in the other 10 (29.4%). At 8 micrograms/ml or less, the elastase production was inhibited completely in 11 (32.4%) strains and more than 50% in the other nine (26.5%). The proliferation was partially inhibited at 32 and 64 micrograms/ml. Roxithromycin inhibited the elastase production at higher concentrations than EM without inhibiting the proliferation. Midecamycin and ampicillin did not inhibit the elastase production or the proliferation. Doxycycline and ticarcillin inhibited the elastase production and/or the proliferation at concentrations greater than 16 micrograms/ml. Although ofloxacin (OFLX) inhibited both the proliferation and the elastase production in parallel at low concentrations, there were six (16.7%) strains resistant to OFLX. Among them the elastase production was inhibited in five strains by EM. These results suggest that EM acts on P. aeruginosa to inhibit extracellular production of elastase without affecting the proliferation of the bacteria.

Cell Division↗

Implications of delayed image on simultaneous thallium-201/technetium-99m pyrophosphate dual emission computed tomography early after acute myocardial infarction.

This study aimed investigate whether thallium-201 and technetium-99m pyrophosphate dual rest-redistribution emission computed tomography early after intracoronary thrombolysis may provide supplementary information for the management of patients with acute myocardial infarction. Fifty patients who received intracoronary thrombolysis underwent simultaneous dual emission computed tomography 3 days after first acute myocardial infarction. All patients who had a technetium-99m pyrophosphate accumulation were selected. Thallium-201/technetium-99m pyrophosphate overlap in the initial and delayed images early after intracoronary thrombolysis identified successful recanalization with sensitivities of 68% and 90% (p < 0.05), specificities of 47% 79% (p < 0.05), positive predictive accuracies of 68% and 88%, negative predictive accuracies of 47% and 80% (p < 0.05), and overall accuracy of 60% and 86% (p < 0.01), respectively. The patients were divided into 3 groups according to the change in thallium-201 uptake from the initial image to the delayed image on dual emission computed tomography: 20 patients had no change in thallium-201 uptake (fixed type), 16 had increases in thallium-201 uptake (redistribution type), and 14 had decreases in thallium-201 uptake (reverse redistribution type). The number of patients with successful recanalization was significantly higher in the redistribution type than in the other types (redistribution type vs reverse redistribution type or fixed type; p < 0.01, respectively). In the redistribution type a frequency of reinfarction in the same infarcted area during the hospital course was significantly higher than in the other types (redistribution type vs reverse redistribution type or fixed type; p < 0.05, respectively), which was mainly due to the patients having high grade residual stenosis. Thus, a thallium-201/technetium-99m pyrophosphate overlap in the delayed image early after acute myocardial infarction can be used as an index for predicting successful early recanalization and probably viable myocardium. In addition, the redistribution patterns on thallium-201 emission computed tomography early after intracoronary thrombolysis can be helpful in identifying patients with successful early recanalization and a high risk subset.

Adult↗

A HTLV-I carrier who showed various symptoms and antibodies of autoimmune diseases.

We report a 37-year-old female HTLV-I carrier with complicating primary biliary cirrhosis (PBC) and mixed connective tissue disease (MCTD). Serum anti-HTLV-I antibody titer was x256. Flower cells (4.5%) were found in the peripheral blood. Southern blot analysis showed no clonal integration in peripheral blood lymphocyte (PBL) DNA. Polymerase chain reaction showed the HTLV-I genome in PBL DNA. As cholestatic liver dysfunction and serum titer of anti-mitochondrial antibody were found, a clinical diagnosis of PBC was made. This patient later developed MCTD. These diseases responded well to prednisone. The pathogenetic relationship of HTLV-I infection with various autoimmune diseases is discussed.

Adult↗

Esthesioneuroblastoma. A report of seven cases.

The biologic behavior of esthesioneuroblastoma in seven patients, treated from 1978 to 1989, is reviewed. The patients were initially treated with surgical resection (2 cases), radiation alone (1 case) or a combination of radiation and surgery (4 cases). The radiation dose ranged from 30 to 62 Gy. Operations were performed via a transmaxillary approach (2 cases), lateral rhinotomy approach (3 cases) and craniofacial approach (1 case). Four of the seven patients experienced local recurrence, occurring after disease-free intervals as long as 6 years. The other three patients died of distant metastasis within one year after initial treatment. The effectiveness of radiation therapy varied, and in some patients a dose of 60 Gy was not enough to control microscopic disease. One patient developed bone marrow metastases which was fatal due to the ensuing pancytopenia. One patient developed a brain metastasis. Hyams' histopathologic staging of the tumor appeared to be related to prognosis.

Adolescent↗

Loxoprofen--another NSAID associated with acute asthmatic death.

Loxoprofen sodium (sodium 2[4-(2-oxocyclopentylmethyl) phenyl] dehydrate; CAS #68767-14-6) is a nonsteroidal, inflammatory drug marketed only in Japan. A case report describes its association with an acute asthmatic death with features resembling those evoked by similar drugs. The analytic methodology is reported. The blood levels of loxoprofen were in the therapeutic range. The tissue concentrations are reported.

Anti-Inflammatory Agents, Non-Steroidal↗

[Method for evaluating pulmonary clearance in mice and its pharmacological applications].

The purpose of this study was to develop a method for evaluating pulmonary clearance in mice that inhaled aerosolized 99mTc-labeled human serum albumin (33mTc-HSA). Mice were ventilated with an aerosol of 99mTc-HSA for 10 min with an ultrasonic nebulizer in an acrylic chamber. Pulmonary clearance was estimated from lung retention ratio at various times after inhalation of 99mTc-HSA. Lung retention ratios in mice were 72.4 +/- 3.3% at 1 hr, 60.1 +/- 2.3% at 3 hr and 34.8 +/- 2.0% at 24 hr after inhalation of 99mTc-HSA, similar to the previous results obtained in humans by cinescintigraphy. The data were analyzed on the basis of two-compartment model. Mabuterol, a beta 2-adrenoceptor agonist, stimulated the pulmonary clearance. In contrast, metyrapone, an adrenal 11-beta steroid hydroxylase inhibitor, suppressed the clearance with a decreased corticosterone content in plasma. These findings suggest that the developed method is useful for evaluating the pharmacological effects on pulmonary clearance.

Adrenergic beta-Agonists↗

[Complication of gastro-duodenum with intra-hepatic arterial infusion chemotherapy using implantable reservoir system for hepatic tumors].

The subjects were 20 cases with implantable reservoir systems for unresectable hepatic tumors. We evaluated the correlation between a complication of the gastro-duodenum after intra-hepatic arterial chemotherapy and a gastro-duodenal distribution of anti-cancer drugs using the hepatic perfusion scintigram by 99mTc-macroaggregated albumin via reservoirs. The 20 cases were divided into 3 groups (A, B, C) according to the level of gastro-duodenal accumulation of 99mTc-MAA. In group A with the strongest accumulation in the gastro-duodenum, we frequently found a gastro-duodenal ulcer after intra-hepatic arterial chemotherapy. There was a significant difference between group A and group C, the latter without a gastro-duodenal accumulation. These results suggested that the hepatic perfusion scintigram via reservoir was a useful examination to expect and prevent the complication of gastro-duodenum on intra-hepatic arterial infusion (especially continuous infusion) chemotherapy.

Carcinoma, Hepatocellular↗

[Efficacy of hemoglobin-Alc, fructosamine, and 1,5-anhydroglucitol in community screening for diabetes mellitus].

To evaluate the efficacy of hemoglobin-Alc, fructosamine, and 1,5-anhydroglucitol tests in screening for diabetes mellitus in communities, the sensitivity and the specificity of these tests were observed on the island of Ojika, Goto islands, Nagasaki prefecture Japan. A 75 gram glucose tolerance test was performed simultaneously on every participant, and WHO diabetes mellitus criteria were used to classify individuals. A total of 554 males and 820 females, older than 34 years, participated in the examination, representing a response rate of 42% and 52% respectively, and 86 were classified as diabetic. The sensitivity and the specificity of several screening levels were determined for each test. Each of the tests attained greater than 70% sensitivity and specificity simultaneously, but could not achieve greater than an 80% level simultaneously. If screening levels are selected for a sensitivity of as low as 50%, it is possible to produce a high specificity of 97-98%. These results provide valuable information for the planning of efficient diabetes mellitus detection programs in communities.

Adult↗

An endothelin B receptor-selective antagonist: IRL 1038, [Cys11-Cys15]-endothelin-1(11-21)

In the inhibition of specific binding of [125I]endothelins (ETs) to membrane from various tissues of rats, guinea pigs, pigs and humans, [Cys11-Cys15]-ET-1(11-21), IRL 1038, has a much higher affinity for ETB receptors (Ki = 6-11 nM) than for ETA receptors (Ki = 0.4-0.7 microM). In contraction assays, with ET-3 as a stimulant, 3 microM IRL 1038 antagonized the ETB receptor-mediated contraction of guinea pig ileal and tracheal smooth muscle without any significant agonistic activity, but did not effect the ETA receptor-mediated contraction of rat aortic smooth muscle. IRL 1038 is therefore, considered to be the first antagonist selective to the ETB receptor.

Amino Acid Sequence↗

Effects of endothelin on cytosolic Ca2+ level and mechanical activity in rat uterine smooth muscle.

The effects of endothelin (ET) on cytosolic Ca2+ level ([Ca2+]i) and mechanical activity were examined in isolated rat uterine smooth muscle. ET-1, ET-2, ET-3 and sarafotoxin S6b (STX) induced rhythmic contractions superimposed on an increased muscle tone. The concentration needed to induce a half-maximum contraction (EC50) was 1.6-3.3 nM for ET-1, ET-2 and STX and higher than 200 nM for ET-3, suggesting that the ET(A) receptor is responsible for these contractions. The sensitivity to ET-1 of uterus at day 20 of gestation was higher than that of non-pregnant rat uterus. Contraction induced by ET-1 followed an increase in [Ca2+]i. The relation between [Ca2+]i and muscle tension, an an indicator of Ca2+ sensitivity of contractile elements, in the presence of ET-1 was identical to that in the presence of high K+ in non-pregnant and pregnant rat uteri. The ET-1-induced increases in [Ca2+]i and muscle tension were strongly inhibited by verapamil in non-pregnant rat uterus. In pregnant rat uterus, however, verapamil only partially inhibited the increases. The verapamil-insensitive portions of [Ca2+]i and contraction were inhibited by EGTA. In the absence of external Ca2+, ET changed neither [Ca2+]i nor muscle tension. These results suggest that ET-1 acts on ET(A) receptors, increase [Ca2+]i and induces contraction without changing Ca2+ sensitivity of contractile elements. The increase in [Ca2+]i seemed to be mediated by opening of L-type Ca2+ channels in non-pregnant rat uterus and also of non-L-type Ca2+ channels in pregnant rat uterus, but not by Ca2+ release from intracellular storage sites.

Animals↗