Biomedical subjects
Publications and source records attributed to M Okuma.
Explore the source record for details and available documents.
The present study was an attempt to elucidate the effect of estrogenic xenobiotics on the proliferation of mitogen-stimulated human peripheral blood lymphocyte (PBL). Our findings follow: (a) the proliferation of PBL in response to phytohemagglutinin (PHA) was mediated by protein kinase C activity, but estrogenic xenobiotics had a strong inhibitory effect on protein kinase C activity of PHA-stimulated PBL; (b) cytoplasmic extracts from PHA-stimulated PBL greatly activated DNA replication, but estrogenic xenobiotics had a strong inhibitory effect on these activities. The results suggest that the cytoplasmic signal-generating system in mitogen-treated PBL is inhibited by estrogenic xenobiotics, and that the defect occurs at all stages in the sequence of events leading to DNA synthesis and cell proliferation.
Explore the source record for details and available documents.
OBJECTIVE: Two-dimensional time-of-flight MR angiography was done with a 1.0 T whole-body imaging system. METHODS: The 10 mm thick presaturation slab was positioned between two sagittal imaging slices of the liver. Images were obtained through the right lobe of the liver by moving the slab and slices together. Each image was acquired during a breath-holding interval of 16 s. RESULTS: Since the directions of the portal and hepatic venous flows are opposite to each other in the right lobe, these two venous systems could be visualized on separate images by the interleaved presaturation slab. On the reconstructed angiograms, separation between the two venous systems was complete and even the fourth and fifth branches were demonstrated clearly. These images facilitate clear understanding of the structure of the intrahepatic blood vessels. CONCLUSION: Although this technique is limited to volunteer studies and works only on the right lobe of the liver, it will provide valuable information for evaluating the location and vascular involvement in various liver diseases.
Platelet survival was studied by using 51Cr-labeled platelets in stroke-prone spontaneously hypertensive rats (SHRSP), stroke-resistant SHR (SHRSR) and normotensive control rats of the Wistar-Kyoto (WK) strain. Relatively young animals of the same age prior to the development of cerebrovascular lesions (cerebral infarction and/or hemorrhage) were used. Platelet half-life time in SHRSP was slightly but significantly shorter than in any other groups or rats, irrespective of the type of platelet donors. Mean platelet consumption was also significantly increased in SHRSP only. Platelets of SHRSP injected into SHRSR showed normal survival. These data support the concept that the shortened platelet survival in SHRSP is brought about by some extracorpuscular abnormalities. Although the vascular changes in SHRSP could be the most likely explanation for the shortened platelet survival, its mechanism remains to be solved. This investigation suggests that studies of the platelet survival in hypertension may be useful in predicting the development of stroke before its clinical recognition.
Thromboxane A2 (TXA2) is a major arachidonic acid metabolite of platelets and induces platelet functions by binding to specific receptors on the membrane. We have found patients with hemostatic defects due to impaired platelet responses to TXA2, and molecular characterization of the patients has been carried out. Platelets from these two unrelated patients showed impaired aggregation responses to TXA2 and its analogues despite the normal response to thrombin. Although the patients' platelets exhibited normal binding activities to TXA2 analogues, they showed decreased GTPase activity and second messenger formation when stimulated by STA2, a stable TXA2 agonist. To understand the molecular basis of this abnormality, we determined the cDNA sequence of the TXA2 receptor by reverse transcription-polymerase chain reaction (RT-PCR) from the patient's platelet RNA, and identified a single amino acid substitution (Arg60 for Leu) in the first cytoplasmic loop of the receptor. This mutation was found in both isoforms of the platelet TXA2 receptor which we have recently found: TXR alpha with the same structure as the placental TXA2 receptor and TXR beta with the same structure as the endothelial TXA2 receptor, and was detected exclusively in affected members of two unrelated families with the disorder. The mutant TXR alpha and TXR beta expressed in COS-m6 cells showed decreased agonist-induced phospholipase C activation despite their normal ligand binding affinities. These results suggest that the Arg60 for Leu mutation is responsible for the disorder and imply a critical role for the first cytoplasmic loop in the interaction of the TXA2 receptor with the G protein.