Search PubMed⌕ Search

Biomedical subjects

A Kubo

Publications and source records attributed to A Kubo.

At least 235 records · Page 13Linked to original sources

[Clinical usefulness of exercise/rest 99mTc-teboroxime SPECT imaging: results of a Japanese multi-center phase II study].

99mTc-Teboroxime [Chloro[tris(cyclohexyldioxime)methaneboronic acid] (99mTc)technetium], a perfusion agent for myocardial imaging, has a distinct advantage over 201Tl because of its very high myocardial extraction and is a 99mTc compound ideal for gamma camera imaging. This agent also demonstrates rapid myocardial washout, which allows completion of exercise and rest imaging studies in a short interval (to 1 hour). However, the rapid washout necessitates the completion of image acquisition very quickly after injection and therefore may require nonconventional SPECT imaging. In this Phase II study we evaluate the safety and efficacy of 99mTc-Teboroxime to detect coronary artery disease by exercise and rest SPECT imaging in 38 patients with prior myocardial infarction, 31 patients with angina pectoris, and 4 patients with non-coronary cardiac diseases. The 99mTc-Teboroxime dose used was 370-740 MBq in each study. The findings were compared with coronary angiography or 201Tl exercise and redistribution SPECT. No significant adverse reactions or laboratory abnormalities attributable to 99mTc-Teboroxime were observed. The quality of SPECT images was optimal in 62.5% of all patients. The relatively large population of suboptimal cases (37.5%) was attributed to the delay of the start and prolongation of the image acquisition time. In 85.7% of patients whose imaging was started within 5 minutes and completed within 11 minutes after injection, optimal quality was observed. Thus, 99mTc-Teboroxime SPECT requires the rapid completion of image acquisition after injection to achieve optimal image quality. Abnormalities of 99mTc-Teboroxime distribution were detected in 97.1% and 62.1% of patients with prior myocardial infarction or angina pectoris, respectively. The concordance with coronary angiography was 84.4% and 68.0%, and with 201Tl was 78.1% and 74.1%, respectively. Although standardization of the image protocol suitable for this agent is needed for the next study, these high correlations suggest the potential usefulness of 99mTc-Teboroxime SPECT imaging.

Adult↗

[Phase 2 clinical study of 99mTc-ECD--a multicenter study].

A phase 2 clinical study of a newly developed brain perfusion agent, 99mTc-ECD, was performed in 166 cases of cerebrovascular diseases and impairment of brain function to evaluate effectiveness, usefulness, optimum dose and optimum timing of imaging as a multi-center study involving 10 institutions in Japan. All cases were judged as no problems on safety and any side effects due to the administration of the compound were not observed. Out of 163 cases evaluated for the clinical usefulness, valuable information for clinical diagnosis was obtained in 160 cases (98.3%), and 154 cases (94.5%) were judged as "extremely useful" or "useful". Although SPECT imaging was possible from 5 min after injection, images obtained between 60 and 90 min after injection showed relatively better image quality in many cases. Regarding standard administration dose, 400 to 800 MBq were considered to be appropriate. 99mTc-ECD is considered to be a promising radiopharmaceutical as a brain perfusion agent.

Adolescent↗

Inhibition of the electron transport system in Staphylococcus aureus by trimethylamine-N-oxide.

Trimethylamine-N-oxide (TMAO) inhibited the growth of Staphylococcus aureus but not of S. epidermidis, which is the main flora in ripening squid, the Japanese traditional sea food Ika-shiokara. This selective inhibition of S. aureus was based on the inhibition of the electron transport system. The cytochrome fraction isolated from S. aureus was converted from the reduced to the oxidized form by the addition of TMAO. It is suggested that the inhibition occurred between cytochrome B and cytochrome o.

Cytochromes↗

[Phase I clinical trial of a new myocardial imaging agent, 99mTc-PPN1011].

A new myocardial imaging agent, 99mTc-1,2-bis[bis(2-ethoxyethyl) phosphino]ethane (99mTc-PPN1011) was administered to healthy male volunteers to evaluate its safety and kinetics. No significant drug-related events were observed. After intravenous injection, blood clearance was rapid. Prompt heart uptake (1.8% of the injected dose after 5 minutes) was followed by relatively slow wash-out (1.0% remained after 3 hours). Liver and lung uptake was observed but the clearance was more rapid than in the heart. 4.7-24.0% of the injected 99mTc-PPN1011 was excreted into urine until 4 hours after injection. 99mTc-PPN1011 also seemed to be excreted through hepato-biliary system. Excellent and low-background myocardial images were obtained using either SPECT or planar imaging. We conclude that 99mTc-PPN1011 could be useful for myocardial perfusion imaging.

Adult↗

[Thallium-201 and gallium-67 scintigraphies in the diagnosis of pneumoconiosis combined with lung cancer].

Thallium-201 (201Tl) and Gallium-67 (67Ga) scintigraphies were performed on 62-year-old male with silicosis combined with lung cancer (squamous cell carcinoma). In 67Ga and early 201Tl images, radiotracer uptakes were observed in both sites of cancer and silicosis, and thus, it was impossible to differentiate cancer mass from the large opacity of pneumoconiosis. On the other hand, in the 201Tl delayed images, 201Tl was localized only in cancer mass, while it was washed out from the large opacity. Our findings indicated that 201Tl early and delayed scintigraphy findings were very useful to differentiate lung cancer from silicosis.

Carcinoma, Squamous Cell↗

[Diagnostic value of a new myocardial perfusion agent, 99mTc-teboroxime (SQ30,217) in patients with coronary artery disease, utilizing a SPECT imaging protocol: a multicenter phase III clinical trial].

Technetium-99m teboroxime (TEBO) is a new technetium-based myocardial perfusion imaging agent, which has high myocardial extraction and rapid myocardial washout. Its rapid myocardial washout may necessitate rapid imaging protocols. This study was designed to perform exercise/rest SPECT imaging protocols with rapid data acquisition (from 2.8 +/- 1.4 min to 11.2 +/- 4.1 min after injection) in 171 patients with coronary artery disease, 15 patients with cardiomyopathy and 8 patients with other heart disease. The rapid imaging protocols resulted in a high prevalence of good image quality. The diagnostic value of TEBO was recognized from the high concordance of image findings with thallium-201 (201Tl) scintigraphy, 88.2% in the exercise protocol and 89.9% in the rest protocol. Also, the sensitivity and specificity of TEBO for detecting coronary artery disease were comparable (86.6% and 53.9%, respectively) with those of 201Tl (90.7% and 46.2%, respectively). No toxic effects of TEBO were observed in subjective and objective clinical findings and blood examinations. TEBO was finally evaluated to be useful in 98.4% of the patients. Thus, this agent has good clinical potential for myocardial perfusion imaging.

Aged↗

[A case of drug-induced esophageal ulcer developed at the esophageal constriction due to the right aortic arch].

A 26-year-old male has a tooth extracted at a dental surgery, and was given 40 mg Froben, as an anti-inflammatory analgesic agent, and ingested one tablet without water. After 2 days, anterior chest pain occurred. Esophagography and endoscopy were performed and multiple esophageal ulcers were confirmed. Esophagography revealed an esophageal stenosis which was considered to be caused by the extramural compression on the oral side of the ulcers. In the chest roentogenography and CT scanning, the right aortic arch was observed. This case was diagnosed as having drug-induced esophageal ulcer developed at the esophageal constriction due to the vascular ring.

Adult↗

[Clinical significance of gallium-67 scintigraphy in assessing pulmonary lesions of sarcoidosis and idiopathic pulmonary fibrosis].

To evaluate whether one can predict the course and prognosis of interstitial lung diseases from lung gallium-67 (67Ga) uptake, we studied 31 subjects with sarcoidosis and 28 with idiopathic pulmonary fibrosis (IPF) retrospectively. We quantified the lung 67Ga uptake using posterior scans by Line's method, and calculated a visual index (VI). The normal range of 67Ga uptake was defined as less than 65 VI values, obtained from the 95 percent confidence interval of the control subjects. All subjects with stage I sarcoidosis, having only bilateral hilar lymphadenopathy (BHL) on chest X-ray, revealed normal lung 67Ga uptake. Fifty percent of patients with stage II sarcoidosis, with both BHL and pulmonary involvement on chest X-ray, showed increased lung 67Ga uptake. The patients with increased lung 67Ga uptake showed decreased percent vital capacity and increased alveolar-arterial oxygen tension difference, but none of them showed clinical deterioration during the follow-up period of more than 6 months. Fifty-four percent of subjects with IPF showed increased lung 67Ga uptake. But there was no difference between the subgroups with normal and increased lung 67Ga uptake with respect to the severity of dyspnea, percent vital capacity, arterial oxygen tension, or alveolar-arterial oxygen tension difference. There was also no difference between the two subgroups of IPF in the cumulative percent survival after either the onset of symptoms or the 67Ga scintigram. We conclude that lung 67Ga uptake was not able to predict the clinical course or the prognosis of patients with sarcoidosis and IPF.

Adult↗

[Reassessment of radionuclide-venography for deep vein thrombosis in the lower extremities and pelvic cavity using 99mTc-MAA].

We performed radioisotope (RI)-venography in 31 patients suspected of deep vein thrombosis (DVT), and 18 patients of them (58.1%) had abnormal findings. Out of the 18 patients, 14 satisfied the diagnostic criteria for DVT, that were interruption in the venous flow with the presence of collateral circulation. Sensitivity, specificity and accuracy of RI-venography for DVT were 100%, 76%, 87%, respectively. In all of the patients with chief complaints of edema and pain in the unilateral extremity DVT was found by RI-venography. Lung scan revealed multiple pulmonary perfusion defects in 4 (33.3%) of 12 patients with DVT. Out of the 4 patients, 3 (75%) had silent pulmonary thromboembolism. 99mTc-MAA accumulation was seen in the left lobe of the liver in a patient with occlusion of the IVC and common iliac veins. We are convinced that patients with PTE and/or edema and pain in the unilateral lower extremity should undergo routine RI-venography. In conclusion, RI-venography using 99mTc-MAA was reassessed and we obtained the result that it is useful for screening and monitoring DVT and pulmonary thromboembolism.

Adolescent↗

[Improvement of bone marrow hematopoiesis in idiopathic myelofibrosis with prednisolone].

A 64 year-old female patient of idiopathic myelofibrosis (IMF), who had had rapidly progressing massive splenomegaly and severe pancytopenia refractory to blood transfusion, was treated with PSL 0.6 mg/kg/day for a month, being significantly improved not only symptomatically and hematologically but also in bone marrow hematopoiesis. Although the effectiveness of PSL to restoration of bone marrow hematopoiesis has been almost unknown, long term oral PSL should be tried for a certain phase of IMF.

Bone Marrow↗

[Usefulness of vitamin A binding protein as a marker for capillary endothelial permeability].

We performed a preliminary study to assess the usefulness of Vitamin A binding protein (VABP) as a gamma-camera marker for capillary endothelial permeability. We used a guinea pig model of endotoxin (LPS) induced acute lung injury. We calculated the concentration ratio of either 125I-albumin or 125I-VABP in lung tissue to that in plasma (tissue plasma ratio; T/P) as a parameter of capillary endothelial permeability. 99mTc-diethylene triamine pentaacetic acid (DTPA) was used as a marker for pulmonary interstitial volume. We estimated wet to dry lung weight ratio as a parameter of lung water accumulation (W/D). LPS increased the T/P of 125I-albumin and W/D, suggesting the development of permeability edema. The T/P for 125I-VABP was also increased, indicating that 125I-VABP can be used to detect elevated capillary endothelial permeability. In both groups, LPS and saline, the T/P was higher for 125I-VABP than for 125I-albumin. These data suggest that the pulmonary capillary endothelium is more permeable to VABP than albumin.

Animals↗

Histamine-induced cyclic AMP accumulation in type-1 and type-2 astrocytes in primary culture.

Histamine-induced cyclic AMP (cAMP) accumulation was studied in purified primary cultures of type-1 and type-2 astrocytes from neonatal rat brain. Histamine induced remarkable cAMP accumulation in type-1 astrocytes in a dose-dependent manner (EC50 = 1.2 x 10(-5) M, Emax = 1100% of control). In contrast, histamine had no significant effect on cAMP accumulation in type-2 astrocytes. Famotidine, an H2-antagonist, dose-dependently inhibited histamine-induced cAMP accumulation in type-1 astrocytes (Ki = 3 x 10(-8) M), but mepyramine (10(-6) M), an H1-antagonist, had no effect. Dimaprit and impromidine, H2-agonists, stimulated cAMP accumulation, but 2-pyridylethylamine, an H1-agonist, did not stimulate it nor augment the H2-agonist-induced cAMP accumulation. These results indicate that (1) histamine induces cAMP accumulation in type-1 astrocytes but not in type-2 astrocytes, and that (2) histamine-induced cAMP accumulation in type-1 astrocytes is mediated by H2-receptors without significant augmentation via H1-receptors.

Animals↗

Two immunologically different isozymes of ascorbate peroxidase from spinach leaves.

Two isozymes of ascorbate peroxidase (AP) from spinach leaves were separated by hydrophobic chromatography and designated AP-I and AP-II. They had similar molecular weights of about 31,000, as determined by gel-filtration, and showed high specificity for ascorbate. One of the two isozymes (AP-II) was purified to homogeneity by SDS-PAGE. Immunoblotting confirmed that antiserum against AP-II reacted with AP-II but not with AP-I. This antiserum inhibited the activity of AP-II, but not that of AP-I. The amino acid composition and partial amino acid sequence of AP-II were determined.

Amino Acid Sequence↗

Histamine H1-receptors on astrocytes in primary cultures: a possible target for histaminergic neurones.

The characteristics of histamine H1-receptors expressed on astrocytes from the cerebral cortex of new born rats were analysed by the [3H]-mepyramine binding assay. The apparent dissociation constant (Kd) was 10.4 nM and the binding capacity (Bmax) of 262 fmol/mg protein. H1-antagonists inhibited the [3H]mepyramine bindings and the isomers of chlorpheniramine showed a stereoselectivity for the inhibition of the bindings. Two distinct populations of cultured astrocytes, type-1 and type-2 astrocytes, were enriched and histamine-induced accumulations of inositol phosphates (IP) and cyclic AMP and histamine-evoked Ca++ signals were examined. Histamine stimulated the accumulation of IP in type-2 astrocytes, but not in type-1 astrocytes. The accumulation of cyclic AMP induced by histamine was observed in type-1 astrocytes, although not in type-2 astrocytes. Histamine-induced Ca++ signals were observed in 17.2% of type-1 astrocytes and in 72.9% of type-2 astrocytes. Histamine-induced Ca++ signals in type-2 astrocytes were antagonized by H1-antagonists, but not by H2- antagonists. Histamine-induced Ca++ signals were classified into 4 patterns, ie. transient, oscillatory, sustained and biphasic. When extracellular Ca++ was omitted or La was added to the extracellular medium, sustained phase of Ca++ signal disappeared and transient and oscillatory patterns were only observed. Phorbol ester inhibited histamine-induced Ca++ signals but pertussis toxin (IAP) and organic voltage dependent Ca++ channel blockers had no effect. Histamine-induced Ca++ elevation appeared initially in processes and then Ca++ wave propagated to the cell soma. Ca++ elevation was observed only in the processes in some cells.

Animals↗

Differences in the probability of cloning specific DNA between primary and amplified libraries: theoretical considerations.

We present a theoretical study of the probability of isolating a particular clone from a DNA library. There are differences in this probability between primary and amplified libraries even if the desired clone represents the same fraction of both libraries. As the result, we must screen severalfold more phage or bacteria in an amplified library than in a primary library.

Cloning, Molecular↗

Adenosine induces System A amino acid transport in cultured rat hepatocytes.

Adenosine caused a 2.5-fold increase in the sodium-dependent uptake of 2-aminoisobutyric acid in rat hepatocytes in primary culture following incubation for 3 h. The range of stimulating concentrations of adenosine corresponded to that of cAMP formation. Adenosine increased the Vmax of the transport without altering the Km for 2-aminoisobutyric acid. These effects of adenosine were abolished by actinomycin D. N6-L-Phenylisopropyladenosine also caused twofold increase in the amino acid transport. These findings suggest that adenosine induces System A amino acid transport in a transcription-dependent manner, and the P1-purinergic receptors are mainly involved in this action of the nucleoside.

Adenosine↗

Inactivation of kanamycin A by phosphorylation in pathogenic Nocardia.

Among the five species of pathogenic Nocardia, i.e., N. asteroides, N. brasiliensis, N. farcinica, N. nova and N. otitidiscaviarum, all strains of N. brasiliensis and N. farcinica showed resistance to an aminoglycoside antibiotic, kanamycin A, showing the MIC (minimum inhibitory concentration) values of more than 100 micrograms/ml. This species-specific difference in sensitivity was found to be explained by the production of an inactivation enzyme, aminoglycoside 3'-phosphotransferase APH(3'). Structural studies by mass and NMR spectroscopy on the inactivated substance produced by a cell-free extract of the Nocardia confirmed the conversion of kanamycin A to an inactive substance, kanamycin A 3'-phosphate. The MIC values of N. otitidiscaviarum and N. nova for kanamycin A, on the other hand, ranged from 0.78 micrograms/ml to 100 micrograms/ml, and both species were non-producers of APH(3'). Sensitivity to the antibiotic and APH(3') productivity of N. asteroides varied depending on the strain.

Carbohydrate Sequence↗

Inhibition of avian myeloblastosis virus reverse transcriptase by heterocyclic quinones: structure-activity correlation.

Synthetic heterocyclic quinones (107 samples) consisting of o- and p-quinoline quinones, o-isoquinoline quinones and p-quinoxaline quinones as well as o- and p-naphthoquinones (3 samples) were tested for their inhibitory activities against avian myeloblastosis virus reverse transcriptase (AMV-RT) and cytotoxic activities against mouse lymphoblastoma L5178Y cells. In general, o-quinoline quinones (i.e., the 5,6-quinolinedione derivatives) are more potent inhibitors of AMV-RT than p-quinoline quinones (the 5,8-quinolinedione derivatives). Furthermore, the growth of L5178/Y cells were significantly refractory to the 8-methoxy-5,6-quinolinedione derivatives whose suppressive effects on AMV-RT function were fairly comparable to those of the other o-quinoline quinones. The longer the chain length of 7-alkyl substituent in o- or p-quinoline quinones, the lower the biological activities.

Avian Myeloblastosis Virus↗