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Biomedical subjects

S Sakuma

Publications and source records attributed to S Sakuma.

At least 19 recordsLinked to original sources

[Biological effects of static gradient magnetic field on cultured mammalian cells and combined effects with 60Co gamma-rays].

The biological effects of a static gradient magnetic field and its combined effects with ionizing radiation on FM3A cultured cells were investigated. The magnetic strength of the center of the field was 5.8 x 10(-2) T esla, the mean gradient of the magnetic filed was 0.6 T esla/m. The magnetic field influenced cell cycle. The relative amount of cultured cells in G1 phase decreased for eight hours after exposure. The growth rate of the cells was slowed by about 5%. Following exposure to the magnetic field, the survival rate of cells decreased to about 20% less than that of the non-exposed control. The combined effect of 60Co irradiation with exposure to the magnetic field showed a greater effect than a simple additive one. The combined effect was influenced by the interval between 60Co irradiation and exposure to the magnetic field. The biological effects of the magnetic field may be related to age-dependent cellular damage in the cell cycle, blockage of cell progression in the cell cycle, and increased repair from radiation damage.

Animals

RFP is a DNA binding protein associated with the nuclear matrix.

We reported that the RFP gene encodes a protein with putative zinc finger domains and was involved in the activation of the ret proto-oncogene. To further characterize the RFP protein, we developed a polyclonal antibody against the product synthesized from a fragment of the RFP cDNA expressed in Escherichia coli. Western blot analysis showed that RFP was identified as a 58 kDa protein in cell lysates from four human and rodent cell lines and from mouse testis. In addition, a unique 68 kDa protein was detected in the testis. Using AH7974 (rat ascites hepatoma) and Raji (human Burkitt lymphoma) cells, we demonstrated strong association of RFP with the nuclear matrix. Furthermore, RFP solubilized from the nuclear matrix had DNA-binding activity although it appears to bind more preferentially to double-stranded DNA than to single-stranded DNA. These results thus suggest that RFP may play a role in molecular processes which occur in the nuclear matrix.

Amino Acid Sequence

[Evaluation of transcatheter arterial embolization with coaxial microcatheter and micro-coil for vascular lesions].

Transcatheter arterial embolization using a coaxial microcatheter and micro-coil was performed in eight patients with vascular lesions; one each with aneurysm of the basilar artery, cerebellar artery, and pancreatic artery, pseudoaneurysm of the common hepatic artery, gastroduodenal artery, and gluteal artery, carotid-cavernous fistula, and thoracic paraspinal arteriovenous malformation. Complete occlusion was achieved in five patients with aneurysm and pseudoaneurysm by occluding the aneurysmal cavity and/or the orifice. A patient with recurrent carotid-cavernous fistula was also completely embolized. A case of basilar artery aneurysm resulted in partial occlusion because the posterior cerebral artery originated from the aneurysm. The unsatisfactory result in a case of paraspinal AVM was due to its wide extension with multiple feeding arteries. No apparent complication was seen. In conclusion, super-selective arterial embolization therapy with coaxial microcatheter and micro-coils was found to be a useful method for vascular lesions that would have been technically difficult to embolize with the standard catheter and coils.

Adult

Alteration of the curved helical structure located in the upstream region of the beta-lactamase promoter of plasmid pUC19 and its effect on transcription.

The region preceding the beta-lactamase promoter of Escherichia coli plasmid pUC19 has a curved DNA (bent DNA) structure. The center of the curvature was revealed to exist around nucleotide position 2580 of the plasmid, which is just beside RNA polymerase binding region. It was indicated that the identified region is curved even at 60 degrees C. The gross geometry of the curvature was altered by inserting synthetic double-stranded oligonucleotides between positions 2585 and 2586. Effect of the alteration on strength of the promoter was not detected in vitro. However, in vivo analyses showed that the promoter strength is apparently dependent, in part, on the gross geometry of the curvature. Insertions of 4 and 16 bp, both of which altered the gross geometry of the curvature greatly, caused considerable reductions of in vivo level of beta-lactamase mRNA. In vivo, overall three-dimensional structure of the region covering the promoter and the curvature seems to play some significant role in transcription of the gene.

Base Sequence

[Time-dose relationship of erythema in high energy photon irradiation therapy].

Skin doses of 100 patients who were treated with high energy ionizing irradiation during conventional irradiation therapy were measured by thermoluminescence dosimeter (TLD). In 87 of the 100 patients, acute hyperemic change of the skin (erythema) of the irradiated region was observed. In the other 13 patients, alopecia of the scalp was observed. The following conclusions were reached. 1) The time-dose relationship was linear when erythema tolerance was used as an index, but not when alopecia was used. 2) The tolerance dose for erythema was lower than previously reported. The slope of the isoeffect curve on the log-log plot of total absorbed skin dose against total number of days after the first irradiation was 0.68 when erythema was used as an index. This number is larger than previously reported results. We considered that erythema is significantly influenced by fraction size and that hyperfractionation is a promising method of irradiation, especially in Japan. 3) Combined use of chemotherapeutic agents, such as 5-Fu, accelerated erythema. The slope of combined treatment was 0.86. Observing acute hyperemic change of skin is considered to be a useful method of investigating the combined effects of chemotherapeutic agents on irradiation.

Dose-Response Relationship, Radiation

Comparison of thallium-201 and technetium-99m teboroxime myocardial single photon emission tomography with coronary arteriography.

Myocardial single photon emission tomography (SPET) using technetium-99m teboroxime (teboroxime) was studied and the results compared with those of thallium-201(thallium) SPET and coronary arteriography in 19 patients. Resting teboroxime SPET was performed initially. Two hours later, exercise teboroxime SPET was performed. Exercise ergometer tests for both teboroxime and thallium were carried out in a supine position. The levels of exercise achieved for both tests were similar. Agreement for the identification of myocardial segments between thallium SPET and teboroxime SPET was 147/171(86%) (NS). When a significant stenosis was defined as greater than or equal to 75% or greater than or equal to 50%, agreement between two radiopharmaceuticals for the detection of diseased vessels was 89% (NS, k = 0.601) or 88% (NS, k = 0.713), respectively. In only 2/19 cases were inferior and posterior segments (3/171) difficult to interpret in teboroxime SPET due to hepatic activity. Thus, teboroxime SPET with a short data acquisition time resulted in a rapid completion for each study and had a good correlation with thallium SPET.

Adult

Hemi-parkinsonism in multiple system atrophy: a PET and MRI study.

We selected 6 patients presenting with hemi-parkinsonism from a total of 20 patients with probable multiple system atrophy (MSA) and studied their nigrostriatal lesions using magnetic resonance (MR) imaging and positron emission tomography (PET) with 18F-labeled 2-deoxy-2-fluoro-D-glucose (FDG). T2 weighted MR images demonstrated a decreased signal intensity in the putamen of all patients. This decreased signal was more intense in the nucleus contralateral to the affected body side in 5 patients. A decreased signal in the substantia nigra was found, expanding more on the contralateral side in 3 patients. T1-weighted images showed that the contralateral putamen was smaller in size than the ipsilateral. These findings indicated that the iron deposit and the neuronal cell loss in the degenerative process were more remarkable in the contralateral nuclei. FDG uptake in 5 patients had likewise declined more in the contralateral than in the ipsilateral putamen. The study shows that these patients have the nigrostriatal lesions as described in previous reports on MSA and that an asymmetric lesion relating to clinical signs is present in the nigrostriatal system. When a patient presents with hemi-parkinsonism alone, MR imaging and PET/FDG are useful for the clinical diagnosis of MSA.

Adult

Inhibition of prostaglandin delta 13 reductase activity in rabbit kidney cortex by glutathione disulfide.

t-Butyl hydroperoxide and H2O2-Fe(2+)-EDTA-glutathione system which produces hydroxyl radicals did not affect the 15-hydroxy prostaglandin dehydrogenase activity in rabbit kidney cortex. On the other hand, H2O2-Fe(2+)-EDTA-glutathione system inhibited the prostaglandin delta 13 reductase activity. Mannitol, a scavenger of hydroxyl radicals, had no effect on the inhibitory action of this system, indicating that the effect of H2O2-Fe(2+)-EDTA-glutathione system on the prostaglandin delta 13 reductase may not be due to produced hydroxyl radicals. As a result of further investigation, it was shown that glutathione disulfide, which is synthesized concomitantly with hydroxyl radicals from H2O2-Fe(2+)-EDTA-glutathione, inhibited the prostaglandin delta 13 reductase activity. These results suggest that hydroperoxides and hydroxyl radicals may not be likely candidates for the modulator of the catabolism of prostaglandins in the kidney cortex, and that glutathione disulfide has the potential to modulate the prostaglandin catabolism by affecting the prostaglandin delta 13 reductase activity.

15-Oxoprostaglandin 13-Reductase

Influence of CRT workstation on observer's performance.

The effects of the operability of the prototype CRT workstation and room illumination upon observer's performance were studied. In the experiment of reading CT images as a routine daily work at the CRT workstation, the average time required to analyse one CT image under a room illuminance of 100 lux was longer than that on the film viewbox. Prolongation occurred due mainly to the longer time required to retrieve and to arrange images as observers desired, and the limitation to the number of images simultaneously displayed on two CRT monitors. In the ROC studies to detect small pulmonary nodules on CRT images of computed radiography with imaging plate, illuminance around 170 lux showed the best result and a statistically significant difference (P less than 0.05) as compared with that of 480 lux. In addition to the radiologist's visual performance, room illumination must also be taken into consideration as it influences the observer's performance and diagnostic efficiency.

Computer Systems

Initial stage of Legg-Calve-Perthes disease: comparison of three-phase bone scintigraphy and SPECT with MR imaging.

Twenty-one patients with initial stage Legg-Calve-Perthes (LCP) disease were examined by three-phase bone scintigraphy, single photon emission scintigraphy (SPECT), and magnetic resonance (MR) imaging. On dynamic study, increased activity was present in the epiphysis or the growth plate in 39%; the corresponding figure for blood-pool images was 94%. Pinhole images demonstrated the lateral stripe of revascularization in 57% of patients. Decreased signal intensity in the epiphysis on T1-weighted images proved to be the most sensitive indicator of epiphyseal necrosis on MR imaging and was absent in only 10% of the cases. The subchondral fracture occurred in 62% (including the above 10% of cases), identified by T1-weighted image. Cartilaginous hypertrophy, detected by T1-weighted image, had a high incidence (81%). Joint effusion was identified on T2-weighted images in 90% of patients. The cross-sectional views provided by SPECT and MR imaging permits a better appreciation of the extent of epiphyseal necrosis in LCP disease.

Bone and Bones

Effect of tert-butyl hydroperoxide on cyclooxygenase and lipoxygenase metabolism of arachidonic acid in rabbit platelets.

The effect of tert-butyl hydroperoxide (t-BOOH) on the formation of thromboxane (TX) B2, 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) from exogenous arachidonic acid (AA) in washed rabbit platelets was examined. t-BOOH enhanced TXB2 and HHT formation at concentrations of 8 microM and below, and at 50 microM it inhibited the formation, suggesting that platelet cyclooxygenase activity can be enhanced or inhibited by t-BOOH depending on the concentration. t-BOOH inhibited 12-HETE production in a dose-dependent manner. When the platelets were incubated with 12-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-HPETE) instead of AA, t-BOOH failed to inhibit the conversion of 12-HPETE to 12-HETE, indicating that the inhibition of 12-HETE formation by t-BOOH occurs at the lipoxygenase step. Studies utilizing indomethacin (a selective cyclooxygenase inhibitor) and desferrioxamine (an iron-chelating agent) revealed that the inhibitory effect of t-BOOH on the lipoxygenase is not mediated through the activation of the cyclooxygenase and that this effect of t-BOOH is due to the hydroperoxy moiety. These results suggest that hydroperoxides play an important role in the control of platelet cyclooxygenase and lipoxygenase activities.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid

Effects of fatty acyl-coenzyme A esters on prostaglandin synthesis in rabbit kidney medulla microsomes.

The effects of fatty acyl-coenzyme A (CoA) esters (palmitoyl-, stearoyl-, oleoyl-, linoleoyl- and arachidonoyl-CoA) on the synthesis of prostaglandins (PGs) in rabbit kidney medulla microsomes were examined. Medulla microsomes were incubated with arachidonic acid in 0.1 M-Tris/HCl buffer (pH 8.0) containing reduced glutathione and hydroquinone and the formed PGE2, PGF2 alpha and PGD2 were measured by high-pressure liquid chromatography using 9-anthryldiazomethane for derivatization. Under our incubation conditions rabbit kidney medulla was found to produce PGE2 mainly. The addition of fatty acyl-CoA esters inhibited total PG formation (the sum of PGE2, PGF2 alpha and PGD2) in a dose-dependent manner. Palmitoyl-, stearoyl- and oleoyl-CoA were about 10 times more potent than linoleoyl- and arachidonoyl-CoA as inhibitors of total PG formation. Linoleic acid was slightly more effective than linoleoyl-CoA, while palmitic acid had no influence on PG formation. All the fatty acyl-CoA esters inhibited the formation of PGE2. Simultaneously, the production of PGF2 alpha and PGD2 was increased. These results suggest that the CoA derivatives of palmitic, stearic and oleic acids have the potential to modulate PGE2, PGF2 alpha and PGD2 synthesis by affecting the activities of both-cyclooxygenase and endoperoxide E2 isomerase.

Acyl Coenzyme A

Usefulness of PET scan in a child with mesial frontal lobe epilepsy.

Positron emission tomography (PET) scan with 18F-fluorodeoxyglucose (18F-FDG) was performed in a 14-year-old boy who had seizures suspected to have originated in mesial frontal lobe. The seizures occurred in clusters and were characterised by a change in the facial expression at seizure onset and complex motor manifestations consisting of kicking, swaying and screaming. Ictal EEG showed rhythmic alpha-waves in the left frontal area association with the ictus. Cerebral CT, MRI and SPECT revealed nothing of significance, but the PET brain scans showed frontal and parietal hypometabolism, which was most prominent in the left mesial frontal lobe. The present case suggests that FDG-PET scanning may be useful for the diagnosis of the mesial frontal epilepsy, when other imaging studies fail to show abnormalities.

Adolescent

Budd-Chiari syndrome with long segmental inferior vena cava obstruction: treatment with thrombolysis, angioplasty, and intravascular stents.

The authors describe a patient with Budd-Chiari syndrome caused by long segmental thrombotic obstruction of the inferior vena cava associated with paroxysmal nocturnal hemoglobinuria. The patient was successfully treated with a combination of local thrombolytic therapy, balloon angioplasty, and placement of Gianturco expandable metallic stents.

Adult

Comparison of Tc-99m HMPAO fast SPECT with Tc-99m HMPAO conventional SPECT in patients with acute stroke.

Tc-99m HMPAO SPECT is more likely to detect a stroke in early stages than CT. However, a conventional HMPAO SPECT study takes at least 30 minutes to complete. This paper compares fast Tc-99m HMPAO SPECT scans and conventional Tc-99m HMPAO SPECT scans with respect to spatial resolution and diagnostic efficacy in vitro and in a small series of patients, respectively. The spatial resolution of fast Tc-99m HMPAO SPECT did not match that of images obtained from conventional SPECT, though the difference proved to be of no clinical significance. Since fast SPECT requires only one-fourth to one-fifth the time necessary for conventional SPECT, it may be more suitable for investigating cases of acute stroke in critical clinical situations.

Acute Disease

Autoradiographic analysis of radiolabeled anti-carcinoembryonic antigen monoclonal antibody CEA102 in colorectal cancer using computed radiography.

Anti-carcinoembryonic antigen monoclonal antibody (MAb) CEA102 was produced by immunization with purified CEA and the specific accumulation of radiolabeled CEA102 in colorectal cancers was investigated by autoradiography of surgical specimens using Fuji Computed Radiography (FCR). Five patients with colorectal cancer were injected intravenously with 131I-labeled intact CEA102 or its F(ab')2. Primary tumor and liver metastases were successfully detected by external scanning with a gamma camera in 4 cases. Autoradiographic study of the surgical specimens using FCR showed predominant localization of 131I-labeled CEA102 in primary tumors and liver metastases in all cases. Even a small liver metastasis (0.5 cm) was clearly visualized in the autoradiogram by FCR. The pixel distribution curves of the density of the respective tissues in the autoradiograms by FCR showed the heterogeneity of the distribution of administered radiolabeled MAb in individual tumors, but the density of the tumors was higher than that of the normal tissues. In the quantitative distribution analysis of CEA102, the uptake of the primary tumor (mean 1.10%ID/kg) was ten-fold greater than that of the normal colon mucosa (mean 0.10%ID/kg). These results revealed that the application of MAb has great potential in radioimmunodetection as well as in antibody-directed therapy.

Adult

Hepatocellular carcinoma: evaluation with color Doppler US and MR imaging.

Fifteen patients with hepatocellular carcinoma underwent examination with color Doppler ultrasound (US), magnetic resonance (MR) imaging, dynamic computed tomography (CT), and angiography. Doppler signals ranging from 0.22 to 3.48 kHz could be obtained from within the tumor in 14 of 15 patients. The resistive index was 0.38-0.77. Color Doppler signals were visualized in nine of 15 lesions with a Doppler shift greater than 0.7 kHz. The Doppler signals and the resistive index of the tumor vessels became lower as the vessels progressed into the center of the lesion. The appearance of tumor vessels recognized on MR images obtained with gradient-recalled acquisition in the steady state (GRASS) in 11 of 15 lesions was compared with that on CT scans and angiograms. Tumors that were hyperintense on GRASS images obtained with a flip angle of 15 degrees transmitted Doppler signals of considerably higher amplitude compared with the isointense lesions. Both color Doppler US and MR imaging provided useful information for characterizing intratumoral blood flow.

Angiography