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Biomedical subjects

M Satake

Publications and source records attributed to M Satake.

At least 55 records · Page 3Linked to original sources

The protooncogene product, PEBP2beta/CBFbeta, is mainly located in the cytoplasm and has an affinity with cytoskeletal structures.

The Pebpb2/Cbfb gene encodes the non-DNA binding beta subunit of the heterodimeric transcription factor, PEBP2/CBF, and has been implicated in a subtype of human acute myeloid leukemia, as well as being indispensable for the development of definitive hematopoiesis in the murine fetal liver. By examining a subcellular localization of the PEBP2beta/CBFbeta protein in tissue culture cells, we could reveal an additional aspect of the protein other than to be a subunit of a transcription factor. Immunoblot and immunocytochemical staining showed that PEBP2beta/CBFbeta was mostly present in the cytoplasm. This PEBP2beta/CBFbeta was free from its DNA-binding partner, the alpha subunit of PEBP2/CBF, as judged by the electrophoretic mobility shift assays. Furthermore, a significant amount of PEBP2beta/CBFbeta was retained in the cytoskeleton preparation after detergent extraction of the cells and was found by double immunofluorescence to colocalize with the F-actin on stress fibers and the vinculin in membrane processes. Thus, the present study extends PEBP2beta/CBFbeta to be a cytoskeleton-affinitive as well as nuclear protein. The implications of these results are discussed.

3T3 Cells

Differentiation dependent expression and distinct subcellular localization of the protooncogene product, PEBP2beta/CBFbeta, in muscle development.

The Pebpb2/Cbfb gene encodes the non-DNA binding subunit of the heterodimeric transcription factor, PEBP2/CBF. To examine the expression of the PEBP2beta/CBFbeta protein in vivo, we carried out immunohistochemistry using the tissues from adult mice as well as embryos. Although PEBP2beta/CBFbeta was detected in various tissues to various degrees, interesting features of expression were observed in the skeletal myogenic cells. Here PEBP2beta/CBFbeta was found mainly to occur as cytoplasmic staining and the intensity of this staining increased depending on the differentiation stage of the cells. In the undifferentiated myoblasts PEBP2beta/CBFbeta was undetectable, whereas moderate levels of PEBP2beta/ CBFbeta were detected in the elongated and aligned myocytes. PEBP2beta/CBFbeta appeared to accumulate further when the cells fused to each other to become multinucleated myotubes. Once the muscle fibers were established, PEBP2beta/CBFbeta was relocated onto or around the Z-lines. PEBP2beta/CBFbeta was also detected in the cytoplasm of cardiac myocytes and in the smooth muscle cells of the digestive tract. In all the above, the skeletal myotubes were the only case that showed both nuclear and cytoplasmic staining of PEBP2beta/CBFbeta. Thus, we could show differentiation dependent pattern of PEBP2beta/CBFbeta expression in muscle development and establish PEBP2beta/CBFbeta to be a cytoplasmic as well as nuclear protein in vivo.

Actinin

Hematopoiesis in the fetal liver is impaired by targeted mutagenesis of a gene encoding a non-DNA binding subunit of the transcription factor, polyomavirus enhancer binding protein 2/core binding factor.

The Pebpb2 gene encodes a non-DNA binding subunit of the heterodimeric transcription factor, polyomavirus enhancer binding protein 2/core binding factor (PEBP2/CBF), and is rearranged in inversion of chromosome 16 associated with human acute myeloid leukemia. To investigate its physiological function, Pebpb2 was mutated by a targeting strategy to generate a null mutant. The homozygous mutation in mice proved lethal in embryos around embryonic day 12.5, apparently due to massive hemorrhaging in the central nervous system. In addition, definitive hematopoiesis in the liver was severely impaired. The observed phenotype was indistinguishable from that reported for homozygous disruption of AML1, which encodes a DNA binding subunit of PEBP2/CBF. Thus, the results indicate that the two subunits function together as a heterodimeric PEBP2/CBF in vivo and that PEBP2/CBF plays an essential role in the development of definitive hematopoiesis.

Animals

New saxitoxin analogues from the freshwater filamentous cyanobacterium Lyngbya wollei.

Along with decarbamoylsaxitoxin and decarbamoylgonyautoxin-2 and -3, six new saxitoxin analogues were isolated from the freshwater mat-forming filamentous cyanobacterium Lyngbya wollei collected from Guntersville Reservoir on the Tennessee River in Alabama. Their structures were determined by electrospray ionization mass spectrometry and several NMR techniques. Five of the toxins contain an acetyl moiety attached to the side chain, which is the first report of these saxitoxin analogues. In three of the toxins a hydrated ketone at C-12 was reduced to alpha-alcohol. The presence of acetate in the side chain resulted in a sevenfold to 17-fold times decrease in mouse toxicity compared to their carbamoyl counterparts, while the reduction at C-12 resulted in a complete loss of mouse toxicity.

Animals

Identification of Protoceratium reticulatum as the biogenetic origin of yessotoxin.

Yessotoxin (YTX), a disulfated polyether toxin, was isolated from cultured cells of the marine dinoflagellate Protoceratium reticulatum and unambiguously identified by high-performance liquid chromatography, 1H NMR, and MS data. The result is the first to confirm toxigenicity of this species and demonstrate it as one of the biogenetic origins of YTX found in shellfish.

Animals

Yessotoxin in mussels of the northern Adriatic Sea.

This study investigated the composition of diarrhoetic shellfish toxins in the hepatopancreas of mussels from the northern Adriatic Sea. The major toxins were shown to be yessotoxin, identified by its chromatographic properties and spectral data, and okadaic acid, detected both by fluorometric high-performance liquid chromatography and by comparison of its spectral properties with those of an authentic sample.

Animals

Antiandrogenic natural Diels--Alder-type adducts from Brosimum rubescens.

The isolation and structure elucidation of five novel natural Diels--Alder-type adducts, named palodesangrens A-E (1-5), from the Peruvian folk medicine known as "palo de sangre" (Brosimum rubescens) is described. The structures of the Diels--Alder adducts, consisting of chalcone derivatives and a prenylcoumarin, were elucidated by analysis of spectroscopic data including 2D NMR. Some of these compounds showed potent inhibitory activity towards 5 alpha-dihydrotestosterone (DHT) binding with an androgen receptor to form a DHT-receptor complex that causes androgen-dependent diseases.

5-alpha Reductase Inhibitors

Pheochromocytoma growing exophytically from the right adrenal gland and invaginating into the liver.

A 5-cm pheochromocytoma located in segment 7 of the liver was found incidentally in a 45-year-old man with mild diabetes mellitus and hypertension, and resected. The tumor was demonstrated by computed tomography and magnetic resonance imaging to have completely invaginated itself into the liver and to be receiving blood from a dilated right hepatic artery alone. Surgery revealed the hepatic mass to be tightly adherent to the right adrenal gland. The histopathologic diagnosis was pheochromocytoma growing exophytically from the right adrenal gland. There was no association with multiple endocrine neoplasia type 1 and type 2. A postoperative 131I metaiodobenzylguanidine scan revealed no accumulation, and the patient is currently doing well without recurrence or hypertension one year after the operation. A pheochromocytoma deeply invaginating into the liver should be considered in the differential diagnosis of primary hypervascular hepatic tumors.

Adrenal Gland Neoplasms

Comparison of commercially available kits with standard methods for detection of Salmonella strains in foods.

Six commercial kits were compared with the U.S. Food and Drug Administration (USFDA) method and the Japanese standard method for Salmonella isolation in foods. When only Salmonella serovars were tested, many of the methods performed well; however, when foods were artificially inoculated, only the USFDA method and immunomagnetic separation coupled with the xylose-lysine-brilliant green agar method (MS-XLBG) could positively detect Salmonella serovars. All seven wild-type Salmonella serovars were detected by the USFDA method, and the MS-XLBG method detected salmonellae from six samples.

Bacterial Typing Techniques

Changes in contrast enhancement of hepatocellular carcinoma and liver: effect of temporary occlusion of a hepatic vein evaluated with spiral CT.

PURPOSE: To assess the hemodynamics of the liver and of hepatocellular carcinomas (HCCs) with hepatic vein occlusion. MATERIALS AND METHODS: Selected hepatic veins were temporarily occluded with a balloon catheter in 21 patients with 28 nontreated nodular HCCs. Computed tomographic (CT) arteriography was performed without and with temporary occlusion of a hepatic vein that drained the blood from segmental liver parenchyma containing tumor by using a unified spiral CT and angiography system. The degree of enhancement and change in appearance of the HCC in each condition were compared. RESULTS: All HCCs were well-enhanced, almost round masses at CT arteriography. At CT arteriography with hepatic vein occlusion, however, HCCs were changed as follows: (a) the absolute attenuation of the HCC was decreased in 27 (96%) of 28 tumors compared with that at CT arteriography without hepatic vein occlusion, while attenuation of the surrounding liver parenchyma was increased; (b) the size of the highly enhanced area in HCC became smaller in 17 (61%) tumors (of these, two disappeared); and (c) the shape was changed in 12 (43%) tumors. CONCLUSION: Hepatic vein occlusion resulted in reciprocal hemodynamic changes in the liver parenchyma relative to HCCs: Enhancement of the liver increases and that of HCCs decreases.

Adult

Hepatocellular carcinoma with portal vein tumor thrombus: embolization of arterioportal shunts.

PURPOSE: To evaluate transcatheter arterial embolization in patients with hepatocellular carcinoma, portal vein tumor thrombus, and arterioportal shunts. MATERIALS AND METHODS: Ten patients with hepatocellular carcinoma, portal vein tumor thrombus, and severe arterioportal shunting were identified; in these patients, portal blood flow before embolization was hepatofugal. Embolization of arterioportal shunts was performed with steel coils that were introduced through a catheter during arteriography. After embolization, changes in portal hemodynamics and clinical signs and performance status of patients were evaluated; survival rates of patients with and patients without severe arterioportal shunting were compared. RESULTS: In all patients after embolization, angiography showed resolution of arterioportal shunting, and portography showed hepatopetal blood flow in the portal vein trunk. After embolization, performance status of five patients with initial scores of 2 or 3 improved. Ascites resolved in four patients and improved in four patients. One patient died of hepatic failure caused by rupture of esophageal varices 7 days after embolization. Median survival was 4.3 months, and the 6-month and 1-year survival rates were 45% and 12%, respectively. There were no significant differences between survival rates in patients with and patients without severe arterioportal shunting. CONCLUSION: Transcatheter arterial embolization of arterioportal shunts is a useful treatment for improving quality of life in patients with hepatocellular carcinoma.

Adult

Connexin32 gene expression in rat sciatic nerves and cultured Schwann cells.

A Western blot analysis showed connexin32 (Cx32) to be present in the myelin membrane. Cx32 mRNA rapidly decreased in the distal segments of crushed sciatic nerves and thereafter returned to normal, as did P0 mRNA. Both Cx32 and P0 mRNAs were detectable in cultured Schwann cells and were enhanced by the addition of forskolin. The developmental profile showed that Cx32 mRNA had thus markedly increased by the time that myelination had become most active, and thereafter only slowly increased unlike P0. Cx32 mRNA seems to parallel myelin size, which thus suggests that Cx32 supports myelin maintenance as a gap junction protein that facilitates the intramyelin exchange of small molecules.

Aging

Antiinflammatory effect of Forsythia suspensa Vahl and its active fraction.

This study was carried out to elucidate the antiinflammatory effect of 70% methanol extract obtained from the dried fruit of Forsythia suspensa Vahl and its active principles. F. suspensa was extracted with 70% methanol and freeze-dried to give a powdered extract. The methanol extract was then dissolved in water and extracted with n-hexane, and the n-hexane fraction was evaporated to dryness under vacuum; the water fraction was freeze-dried to give a powdered extract. The antiinflammatory activity of the extract and fractions was investigated on acetic acid-induced vascular permeability and writhing symptoms in mice, as well as on carrageenin-induced edema and cotton pellet-induced granuloma formation in rats. The methanol extract and the n-hexane fraction (p.o.) showed the antiinflammatory effect and analgesic effect, but the water fraction did not. These results suggested that the antiinflammatory and analgesic activity induced by the methanol extract shifted to the n-hexane fraction and the active principles may be lipophilic compounds.

Acetic Acid

[A case report of alternating abducens hemiplegia with special reference to the supranuclear pathway to the facial nucleus].

A case of alternating abducens hemiplegia was reported. A 16-year-old girl developed alternating hemiplegia characterized by the left abducens nerve palsy and right hemiparesis. In addition, she had right supranuclear facial nerve palsy. A brain MRI showed left mid to lower pontine lesion and vertebral angiography revealed medullary venous malformation in the left pons. SEP with right posterior tibial nerve stimulation showed a delayed central conduction time, suggesting that the lesion involved left medial lemniscus. We previously reported a 39-year-old man who developed pure alternating abducens hemiplegia. He did not show supranuclear facial nerve palsy or SEP abnormality. These findings support the idea that the supranuclear facial nerve fiber leaves the pyramidal tract at the upper to middle pons and descends in the area of the pontine tegmentum around the medial lemniscus.

Abducens Nerve

[Staging of pancreatic ductal adenocarcinoma using dynamic MR imaging].

Single breath-hold gradient echo images were obtained before and immediately after bolus intravenous administration of Gd-DTPA (dynamic MR imaging) in the study of the pancreas. Of 37 patients with pathologically proved pancreatic ductal adenocarcinoma, seventeen patients who underwent both dynamic MR imaging studies and curative surgery were included in this study. Correlations between histologic findings in the resected specimens and MR images were analyzed as to tumor extension and staging according to the General Rules for the Study of Pancreatic Cancer (4th Edition) published by the Japan Pancreas Society. In comparison with conventional MR images, dynamic MR imaging improved the detectability of pancreatic carcinoma and delineation of the vasculature by clarifying the margin of the tumor and the vessels. Nonenhanced T1-weighted imaging is the best sequence to estimate peripancreatic tumor extension, because the contrast between the tumor and peripancreatic fat deteriorates with the use of contrast material. There is a tendency to overestimate vascular invasion on MR images, the reason for which is considered to be the contractive nature of fibrotic change induced by pancreatic carcinoma. The diagnostic efficacy of lymph node metastasis remains insufficient on MR images because some cases show no enlargement of lymph nodes in spite of the existence of pathological metastasis. Our results suggest that dynamic MR imaging has the advantage of improving the conspicuity of the tumor and the vasculature.

Adult