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Biomedical subjects

S Sakuma

Publications and source records attributed to S Sakuma.

At least 181 records · Page 10Linked to original sources

Effect of 13-hydroperoxyoctadecadienoic acid on 15-hydroxy prostaglandin dehydrogenase activity in rabbit kidney cortex.

The effect of a hydroperoxy adduct of linoleic acid, 13-hydroperoxyoctadecadienoic acid (13-HPODE), on 15-hydroxy prostaglandin dehydrogenase activity in rabbit kidney cortex was examined. 13-HPODE inhibited the 15-hydroxy prostaglandin dehydrogenase activity at concentrations ranging from 1 to 10 microM. The effect was concentration-dependent and the concentration required for 50% inhibition was approximately 3 microM. Linoleic acid and 13-hydroxyoctadecadienoic acid (13-HODE) exhibited weaker inhibition of the enzyme activity than did 13-HPODE (linoleic acid, 30% inhibition at 10 microM; 13-HODE, 45% inhibition at 10 microM). Studies utilizing Fe2+ (a catalyst of peroxide decomposition), and mannitol or dimethylsulfoxide (a hydroxy radical scavenger) revealed that the inhibitory effect of 13-HPODE on the 15-hydroxy prostaglandin dehydrogenase activity is not due to the hydroxy radicals which are expected to be formed from 13-HPODE and that the hydroperoxy functional group is a prerequisite. The inhibition by 13-HPODE was uncompetitive and non-competitive with regard to NAD+ and prostaglandin E2, respectively. These results suggest that 13-HPODE has the potential to modulate the prostaglandin catabolism by affecting the 15-hydroxy prostaglandin dehydrogenase activity.

Animals↗

Effects of reactive oxygen species on arachidonic acid metabolism in rabbit platelets.

Rabbit platelets were exposed to a reactive oxygen species (ROS) generating system (xanthine plus xanthine oxidase) to explore the effect of ROS on the formation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), thromboxane (TX) B2, and 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) from exogenous arachidonic acid. Xanthine plus xanthine oxidase suppressed the production of 12-HETE, TXB2, and HHT by 65-69%. This effect was reversed by addition of catalase to the ROS generating system but not by superoxide dismutase, mannitol, or dimethylsulfoxide, indicating that H2O2 is the responsible metabolite. These results suggest that H2O2 plays an important role in the regulation of platelet cyclo-oxygenase and lipoxygenase activities.

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

Myocardial SPECT and left ventricular performance study using a single Tc-99m teboroxime injection. Comparison with thallium-201 myocardial SPECT.

Myocardial SPECT using teboroxime was compared to thallium SPECT in 26 patients undergoing cardiac catheterization. Agreement between thallium SPECT and teboroxime SPECT for the identification of myocardial segments was 209/235 (89%). A significant correlation was found in 15 patients between the left ventricular ejection fraction by teboroxime first-pass study and the ejection fraction by contrast ventriculography. In nine patients with myocardial infarction and/or multivessel coronary artery disease, the ejection fraction revealed a mean decrease from 0.52 at rest to 0.46 at exercise. Teboroxime makes it possible to perform an exercise first-pass study of left ventricular ejection fraction followed by myocardial perfusion imaging.

Adult↗

Inducible expression of a foreign gene inserted into the human cytomegalovirus genome.

We previously described the insertion of a foreign gene into a non-essential region of human cytomegalovirus (HCMV) by homologous recombination. Here we report insertion of the Escherichia coli lacZ gene downstream of the mouse metallothionein promoter into the HindIII-O region of HCMV by replacement-type recombination. Expression of the lacZ gene in the recombinant was independent of viral growth, but dependent on induction by heavy metals. Of several metals tested for beta-galactosidase induction and also for their toxicity to HEL cells, Zn was found to be the most suitable for use as an inducer. In HEL cells infected with the recombinant in the presence of 50 microsM-Zn, beta-galactosidase activity was maximal 3 days after infection, and reached levels 27 times higher than the value obtained in the absence of Zn.

Cytomegalovirus↗

Immunohistochemical observations of macrophages and perisinusoidal cells in carbon tetrachloride-induced rat liver injury.

In rat liver injured by carbon tetrachloride, ED-1-positive monocytes and resident macrophages significantly increased in number in damaged perivenular zones on days 2 and 4 after single or double dosing, peaking on day 2 and being two-fold more after the 2nd dosing. ED-2-positive resident macrophages significantly increased in number only on day 4 after the single dosing and on days 2, 4 and 6 after the 2nd dosing with a peak on day 2. A significant increase in number of muscle actin-positive perisinusoidal cells was seen on day 4 and on days 2 and 4 after the 1st and 2nd dosings, respectively, reaching a peak on day 4 and being more remarkable after the 2nd dosing.

Actins↗

Human glioblastoma cells produce granulocyte-macrophage colony-stimulating factor in vitro, but not in vivo, without expressing its receptor.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) production and receptor expression by human glioblastomas was studied. Enzyme-linked immunosorbent assay showed four of 10 glioblastoma cell lines spontaneously released GM-CSF (2.9-9.2 pg GM-CSF protein/ml culture medium), which was enhanced by stimulation with tumor necrosis factor-alpha (TNF) (10 U/ml) up to 410 pg/ml. TNF also induced secretion of GM-CSF by another cell line. Northern blot analysis identified increasing GM-CSF gene expression by cells following TNF stimulation. However, no GM-CSF protein was detectable in the cerebrospinal fluid of three malignant glioma patients. Intratumoral administration of TNF in the patients also failed to stimulate GM-CSF levels in the cerebrospinal fluid. A binding assay using flow cytometry with biotinylated GM-CSF and Scatchard analysis using 125I-labeled GM-CSF failed to demonstrate GM-CSF receptor expression on the 13 cell lines. Exogenous GM-CSF stimulation had no effect on production of prostaglandin E2, interleukin-6, or interleukin-8 by glioma cells. Human glioblastoma cells secrete GM-CSF without expressing the receptor in vitro, but there was no evidence of GM-CSF production in vivo.

Glioblastoma↗

Thyroid nodules: evaluation with color Doppler ultrasonography.

Forty-seven patients with thyroid nodules (13 papillary carcinomas, 14 adenomas, and 20 adenomatous goiters) underwent color Doppler sonography with a 7.5 MHz transducer. Perinodular or intranodular color flow signals were depicted in 10 of 13 papillary carcinomas, in 10 of 14 follicular adenomas, and in 14 of 20 adenomatous goiters. No correlation existed between the presence of color signals and pathology, whereas the detection rate of color signals had a dependence on the size of the lesions. No specific flow pattern for malignancy could be found. Color Doppler sonography would not improve the ability to differentiate benign from malignant nodules significantly.

Adenoma↗

Considerations for standard chest radiography: the long film-focus distance technique.

The possibility of using long film-focus distance radiography as a new screening method for lung cancer diagnosis was investigated. Long-film focus distance radiography produced exceptionally superior image sharpness suitable for use as clinical photographs, at a distance of about FFD (Film-Focus Distance) 20 m. The effective energy was increased by narrowing the radiation spectrum via an air-filter effect, which may prove useful in reducing radiation exposure dosage. Questionnaire results indicate good visualization of cardiac posterior and trachea shadow regions in the diaphragm. Further study is required regarding methods for stabilizing patient position and synchronization with heart beat and respiration to improve reproducibility.

Humans↗

[Radioimmunodetection of colorectal cancer, using anti-CEA monoclonal antibody CEA102: experience of 20 cases].

The monoclonal antibody CEA 102 against carcinoembryonic antigen was produced by immunization with purified CEA, and used as a radiotracer for the imaging of colorectal cancer. CEA102 was labeled with 131I by the chloramine-T or the Iodogen method, and administered i.v. to 20 patients with liver metastases, local recurrences, and/or primary tumors. Planar scintigraphy was performed during 5 or 6 postinfusion days. Hypersensitivity reactions such as fever and chill occurred in 4 patients, but no side effects were noted after endotoxin was excluded. Overall sensitivity was 71.4% (primary tumor 4/4, liver metastasis 5/6, lymph node metastasis 1/1, local recurrence 5/10), and no false positive was observed. In the cases of local recurrences, this method was useful to distinguish postoperative fibrosis from local recurrence. These results revealed that radiolabeled CEA102 has a great potential in qualitative diagnosis of colorectal cancer.

Adult↗

[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↗