Biomedical subjects

T Nagao

Publications and source records attributed to T Nagao.

At least 91 records · Page 5Linked to original sources

PubMed2000

Interaction with beta-arrestin determines the difference in internalization behavor between beta1- and beta2-adrenergic receptors.

The beta(1)-adrenergic receptor (beta(1)AR) shows the resistance to agonist-induced internalization. As beta-arrestin is important for internalization, we examine the interaction of beta-arrestin with beta(1)AR with three different methods: intracellular trafficking of beta-arrestin, binding of in vitro translated beta-arrestin to intracellular domains of beta(1)- and beta(2)ARs, and inhibition of betaAR-stimulated adenylyl cyclase activities by beta-arrestin. The green fluorescent protein-tagged beta-arrestin 2 translocates to and stays at the plasma membrane by beta(2)AR stimulation. Although green fluorescent protein-tagged beta-arrestin 2 also translocates to the plasma membrane, it returns to the cytoplasm 10-30 min after beta(1)AR stimulation. The binding of in vitro translated beta-arrestin 1 and beta-arrestin 2 to the third intracellular loop and the carboxyl tail of beta(1)AR is lower than that of beta(2)AR. The fusion protein of beta-arrestin 1 with glutathione S-transferase inhibits the beta(1)- and beta(2)AR-stimulated adenylyl cyclase activities, although inhibition of the beta(1)AR-stimulated activity requires a higher concentration of the fusion protein than that of the beta(2)AR-stimulated activity. These results suggest that weak interaction of beta(1)AR with beta-arrestins explains the resistance to agonist-induced internalization. This is further supported by the finding that beta-arrestin can induce internalization of beta(1)AR when beta-arrestin 1 does not dissociate from beta(1)AR by fusing to the carboxyl tail of beta(1)AR.

Adenylyl Cyclases↗

PubMed2000

Geoelectric potential changes: possible precursors to earthquakes in Japan.

Whether electromagnetic precursors to earthquakes (EQs) exist is an important question not only for EQ prediction but also for understanding the physical processes of EQ generation. Slow transient geoelectric potential changes have been observed before several recent EQs in Japan. In most cases, they appeared 1-19 days before the EQs, and their duration and intensity were several minutes to 1 h and 1-2 mV/100 m. The changes appeared before five of all six EQs with magnitude >/= 5 that occurred within 20 km of our stations during the observation period. Changes were also detected at greater epicentral distances (up to 75 km) before two other EQs, including one EQ of magnitude 4.7, which was preceded by a signal simultaneously recorded at three widely separated stations. These geoelectric potential changes have been distinguished through the following criteria from a multitude of other changes, which were noise of various origins. (i) The selected changes were proportional in amplitude to the length of the recording station's short ( approximately 100 m) dipoles and were simultaneously detected also on long (1-10 km) dipoles when the latter were in operation. (ii) No such changes occurred during the observation period that were not followed by EQs. Although the EQ precursory nature of these geoelectric potential changes is admittedly unproven, it seems that the present results warrant continued serious research into the occurrence, generation, and transmission of these signals and their possible causal relationship to EQs.

Disasters↗

PubMed2000

Molecular cloning and characterization of a novel chloride intracellular channel-related protein, parchorin, expressed in water-secreting cells.

We previously reported a 120-kDa phosphoprotein that translocated from cytosol to the apical membrane of gastric parietal cells in association with stimulation of HCl secretion. To determine the molecular identity of the protein, we performed molecular cloning and expression of the protein. Immunoblot analysis showed that this protein was highly enriched in tissues that secrete water, such as parietal cell, choroid plexus, salivary duct, lacrimal gland, kidney, airway epithelia, and chorioretinal epithelia. We named this protein "parchorin" based on its highest enrichment in parietal cells and choroid plexus. We obtained cDNA for parchorin from rabbit choroid plexus coding a protein consisting of 637 amino acids with a predicted molecular mass of 65 kDa. The discrepancy in size on 6% SDS-polyacrylamide gel electrophoresis is considered to be due to its highly acidic nature (pI = 4.18), because COS-7 cells transfected with parchorin cDNA produced a protein with apparent molecular mass of 120 kDa on 6% SDS-polyacrylamide gel electrophoresis. Parchorin is a novel protein that has significant homology to the family of chloride intracellular channels (CLIC), especially the chloride channel from bovine kidney, p64, in the C-terminal 235 amino acids. When expressed as a fusion protein with green fluorescent protein (GFP) in the LLC-PK1 kidney cell line, GFP-parchorin, unlike other CLIC family members, existed mainly in the cytosol. Furthermore, when Cl(-) efflux from the cell was elicited, GFP-parchorin translocated to the plasma membrane. These results suggest that parchorin generally plays a critical role in water-secreting cells, possibly through the regulation of chloride ion transport.

Amino Acid Sequence↗

PubMed2000

Translocation of HSP27 to sarcomere induced by ischemic preconditioning in isolated rat hearts.

We investigated the role of the 27-kDa heat shock protein (HSP27) in cardiac protection using Langendorff-perfused rat hearts. After preconditioning (a single episode of 5 min global ischemia followed by 5 min of reperfusion), HSP27 redistributed from the cytosol to the sarcomere and recovery of the contractile function, after 40 min of global ischemia and 50 min of reperfusion, was significantly enhanced. Both SB203580, a p38 MAP kinase inhibitor, and bisindolylmaleimide I, a protein kinase C inhibitor, prevented the effects of preconditioning. Both 2-chloro-N(6)-cyclopentyladenosine (adenosine A1 agonist) and anisomycin (activator of p38 MAP kinase and c-jun N-terminal kinase) mimicked preconditioning. These results suggest that activation of protein kinase C followed by activation of p38 MAP kinase elicits translocation of HSP27 to the sarcomere, a process which may be involved in the cardioprotective mechanism afforded by ischemic preconditioning in rat heart.

Animals↗

PubMed2000

Genetic control of development of the mushroom bodies, the associative learning centers in the Drosophila brain, by the eyeless, twin of eyeless, and Dachshund genes.

Mushroom bodies (MBs) are the centers for olfactory associative learning and elementary cognitive functions in the Drosophila brain. By high-resolution neuroanatomy, we show that eyeless (ey), twin of eyeless, and dachshund (dac), which are implicated in eye development, also are expressed in the developing MBs. Mutations of ey completely disrupted the MB neuropils, and a null mutation of dac resulted in marked disruption and aberrant axonal projections. Genetic analyses demonstrated that, whereas ey and dac synergistically control the structural development of the MBs, the two genes are regulated independently in the course of MB development. These data argue for a distinct combinatorial code of regulatory genes for MBs as compared with eye development and suggest conserved roles of Pax6 homologs in the genetic programs of the olfactory learning centers of complex brains.

Animals↗

PubMed2000

Possible mechanism of congenital malformations induced by exposure of mouse preimplantation embryos to mitomycin C.

ICR mice were treated intraperitoneally with mitomycin C at 5 mg/kg on day 3 of gestation. On day 18 of gestation, fetuses of treated dams were inspected for external, skeletal and visceral malformations. At 6 or 12 hr after mitomycin C treatment, the blastocysts were obtained from the uteri of treated dams and the degenerated cells within inner cell mass (ICM) and trophectoderm (TE) tissues were examined microscopically. On day 5, 8, 11, or 18 of gestation, the uteri of treated dams were obtained and those including embryos/fetuses and placentae were examined histologically. Finally, on each of gestational days 5-14, the blood of the treated dams was collected and the hematological parameters determined. Pre- and postimplantation losses in the dams treated with mitomycin C were significantly increased; increased frequency of abdominal wall defects and lumbar ribs in term fetuses, decreased fetal weight, and increased placental weight were noted as well. No significant increase in visceral malformations was found in term fetuses treated with mitomycin C. Frequency of degenerated cells within ICM and TE of blastocysts from dams treated with mitomycin C was significantly increased as compared with the controls. In dams treated with mitomycin C, decidua developed insufficiently and the trophoblast giant cell layer was not separated from the uterine lumen by maternal components; hemorrhage from the denuded trophoblast giant cell layer into the uterine lumen was noted. The number of erythrocytes, as well as hemoglobin concentration, hematocrit, and the percentage of reticulocytes in blood of dams treated with mitomycin C were significantly lower from days 6-12 of gestation, as compared with controls. The results of the present study showed that an increase in number of degenerated cells within blastocysts results in preimplantation loss and both maternal and embryonic hypoxia during major organogenesis results in postimplantation loss and congenital fetal malformations.

Abnormalities, Drug-Induced↗

PubMed2000

Coronary artery bypass grafting in patient with malignant neoplasm. Efficacy of coronary artery bypass grafting on beating heart.

OBJECTIVE: Coronary artery bypass grafting (CABG) prior to noncardiac major surgery has effectively decreases short- and long-term mortality related to coronary ischemia. Coronary artery bypass on the beating heart is conducted to avoid the risk of cardiopulmonary bypass and it has contribute to shorten recovery time. METHODS: Subjects were 19 patients with malignant neoplasm for whom a retrospective chart review was made between Jan. 1, 1992 and July 31, 1998. In the early phase of this study, between Jan. 1, 1992, and Dec. 31, 1997, CABG was performed using cardiopulmonary bypass, and late phase, between Jan. 1, 1998, and July 1, 1998, CABG was done on the beating heart without cardiopulmonary bypass. RESULTS: Conventional CABG was performed in 12 patients with neoplasms (10 male and 2 female, age 64.7 +/- 6.1 years), and CABG on the beating heart was performed in 7 patients (6 male and 1 female, age 68.0 +/- 7.5 years). Fewer number of bypass grafts were made in the beating-heart CABG group (1.3 +/- 0.5 in beating-heart CABG versus 3.9 +/- 1.1 in conventional CABG). No cardiac events occurred in either group during the surgery for malignant tumors. The operative interval between CABG and cancer surgery was significantly shorter in the beating-heart CABG group (21.8 +/- 17.9 days in beating-heart CABG versus 53.5 +/- 42.9 days in conventional CABG, p < 0.05). CONCLUSION: Patients with severe coronary artery disease and malignant neoplasms should undergo coronary artery revascularization before the neoplasm is treated. CABG on the beating-heart was safe and effective procedure in those with malignant neoplasms.

Aged↗

PubMed2000

Variation among giant rice bodies: report of four cases and their clinicopathological features.

OBJECTIVE: To report four cases of rice bodies (RBs) showing remarkable size variations and discuss their pathogenesis. DESIGN AND PATIENTS: Based on analysis of the clinical data, we speculate on the pathogenesis of RBs using immunohistochemical and ultrastructural methods. The patients comprised three men and one woman, three with RBs in the subacromial bursae and one in the wrist synovial sheath, aged 28 (woman), 44, 50 and 81 (wrist) years, respectively. RESULTS: There were no particular differences in clinical data among the patients. T2-weighted MR imaging was very useful for diagnosis of the RBs, allowing their clear delineation from the bursal fluid. The RBs consisted of a layered protein- aceous substance with vague targetoid cut surfaces. Much fibrin and a lesser amount of collagen fibers were recognized together with various mononuclear cells, which were few in number and predominantly T cells. The bursae and synovial sheath had multiple fibrinoid spheroids at the luminal surface. CONCLUSION: Fibrinoid nodular deposits probably became detached, forming the nuclei of RBs and growing to a giant RB 65 mm in diameter.

Adult↗

PubMed2000

Patterning defects in the primary axonal scaffolds caused by the mutations of the extradenticle and homothorax genes in the embryonic Drosophila brain.

During early brain development in Drosophila a highly stereotyped pattern of axonal scaffolds evolves by precise pioneering and selective fasciculation of neural fibers in the newly formed brain neuromeres. Using an axonal marker, Fasciclin II, we show that the activities of the extradenticle (exd) and homothorax (hth) genes are essential to this axonal patterning in the embryonic brain. Both genes are expressed in the developing brain neurons, including many of the tract founder cluster cells. Consistent with their expression profiles, mutations of exd and hth strongly perturb the primary axonal scaffolds. Furthermore, we show that mutations of exd and hth result in profound patterning defects of the developing brain at the molecular level including stimulation of the orthodenticle gene and suppression of the empty spiracles and cervical homeotic genes. In addition, expression of a Drosophila Pax6 gene, eyeless, is significantly suppressed in the mutants except for the most anterior region. These results reveal that, in addition to their homeotic regulatory functions in trunk development, exd and hth have important roles in patterning the developing brain through coordinately regulating various nuclear regulatory genes, and imply molecular commonalities between the developmental mechanisms of the brain and trunk segments, which were conventionally considered to be largely independent.

Animals↗

PubMed2000

Tuberculous peritonitis defying diagnosis: report of a case.

A case of tuberculous peritonitis, which has been scarcely encountered in clinical practice in recent years, is reported. A 32-year-old man was admitted to our hospital complaining of abdominal fullness, anorexia, and a 15 kg weight loss. His abdomen was distended. There was neither any previous history nor recent contact with tuberculosis. The laboratory data indicated increased C-reactive protein and erythrocyte sedimentation rate, but the white blood cell count was normal. A chest X-ray examination revealed no abnormalities. Abdominal X-ray showed scattered, small-intestinal gas shadows. Abdominal computed tomography scanning revealed a diffuse thickening of the dilated bowel wall, mainly adjacent to the mesentery. After a detailed examination a diagnosis of peritonitis carcinomatosa of unknown origin was suspected, and an exploratory laparotomy was done. Severe adhesions between the parietal peritoneum and the bowel were found. An excisional biopsy specimen was taken from the peritoneum, and a diagnosis of tuberculosis was thus made. Triple therapy with isoniazid, rifampicin, and kanamycin was started, and both the intestinal obstruction and anorexia were thus resolved.

Adult↗

PubMed2000

Surgical management of unstable patients in the evolving phase of acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) can be treated with thrombolysis or coronary catheter intervention; surgical treatment--coronary artery bypass grafting (CABG)--is reserved for the patients in whom other procedures have failed. We performed CABG in 47 patients during the evolving phase of AMI, and analyzed their short-term and long-term results. METHODS: Preoperative, intraoperative, and postoperative data were analyzed in patients who underwent emergency CABGs for AMI between January 1, 1992, and July 31, 1998. CABGs performed more than 7 days after AMI were excluded from this study. RESULTS: The subjects were 47 patients (33 males and 14 females) with AMI who were treated by emergency CABG. Intraaortic balloon pumping was used in 44 cases and percutaneous circulatory pulmonary support was used in 3 cases. The mean interval between the onset of AMI and surgery was 27.4 +/- 27.9 hours. The mean number of bypass grafts was 3.0 +/- 1.1, and at least 1 arterial conduit was used in 45 cases (95.7%). Aortic clamp time, pump time, and operative time were 64.7 +/- 31.7, 117.3 +/- 55.2, and 313.2 +/- 84.8 minutes, respectively. IABP or percutaneous cardiopulmonary support were removed in the intensive care unit (ICU) 30.0 +/- 28.9 hours after CABG. The patients were extubated 41.4 +/- 40.5 hours after surgery, remained in ICU for 4.7 +/- 2.7 days, and were discharged from the hospital after 27.0 +/- 22.5 days. Three patients died from multiorgan failure related to postoperative sepsis, and 8 cases of major complications were observed. The actuarial 5-year survival rate of the patients treated with CABG was 83.0%. CONCLUSIONS: Surgical treatment in the unstable patients after AMI can be performed with acceptable risk. Arterial revascularization may contribute to improvement in long-term results.

Aged↗

PubMed2000

Conformation and dynamics of melittin bound to magnetically oriented lipid bilayers by solid-state (31)P and (13)C NMR spectroscopy.

The conformation and dynamics of melittin bound to the dimyristoylphosphatidylcholine (DMPC) bilayer and the magnetic orientation in the lipid bilayer systems were investigated by solid-state (31)P and (13)C NMR spectroscopy. Using (31)P NMR, it was found that melittin-lipid bilayers form magnetically oriented elongated vesicles with the long axis parallel to the magnetic field above the liquid crystalline-gel phase transition temperature (T(m) = 24 degrees C). The conformation, orientation, and dynamics of melittin bound to the membrane were further determined by using this magnetically oriented lipid bilayer system. For this purpose, the (13)C NMR spectra of site-specifically (13)C-labeled melittin bound to the membrane in the static, fast magic angle spinning (MAS) and slow MAS conditions were measured. Subsequently, we analyzed the (13)C chemical shift tensors of carbonyl carbons in the peptide backbone under the conditions where they form an alpha-helix and reorient rapidly about the average helical axis. Finally, it was found that melittin adopts a transmembrane alpha-helix whose average axis is parallel to the bilayer normal. The kink angle between the N- and C-terminal helical rods of melittin in the lipid bilayer is approximately 140 degrees or approximately 160 degrees, which is larger than the value of 120 degrees determined by x-ray diffraction studies. Pore formation was clearly observed below the T(m) in the initial stage of lysis by microscope. This is considered to be caused by the association of melittin molecules in the lipid bilayer.

Amino Acid Sequence↗

PubMed2000