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Biomedical subjects

S Uchiyama

Publications and source records attributed to S Uchiyama.

At least 37 records · Page 2Linked to original sources
PubMed2001

Anabolic steroids increase exercise tolerance.

The influence of an anabolic androgenic steroid (AAS) on thymidine and amino acid uptake in rat hindlimb skeletal muscles during 14 days after a single exhaustive bout of weight lifting was determined. Adult male rats were divided randomly into Control or Steroid groups. Nandrolone decanoate was administered to the Steroid group 1 wk before the exercise bout. [3H]thymidine and [14C]leucine labeling were used to determine the serial changes in cellular mitotic activity, amino acid uptake, and myosin synthesis. Serum creatine kinase (CK) activity, used as a measure of muscle damage, increased 30 and 60 min after exercise in both groups. The total amount of weight lifted was higher, whereas CK levels were lower in Steroid than in Control rats. [3H]thymidine uptake peaked 2 days after exercise in both groups and was 90% higher in Control than in Steroid rats, reflecting a higher level of muscle damage. [14C]leucine uptake was approximately 80% higher at rest and recovered 33% faster postexercise in Steroid than in Control rats. In a separate group of rats, the in situ isometric mechanical properties of the plantaris muscle were determined. The only significant difference was a higher fatigue resistance in the Steroid compared with the Control group. Combined, these results indicate that AAS treatment 1) ameliorates CK efflux and the uptake of [3H]thymidine and enhances the rate of protein synthesis during recovery after a bout of weight lifting, all being consistent with there being less muscle damage, and 2) enhances in vivo work capacity and the in situ fatigue resistance of a primary plantarflexor muscle.

Anabolic Agents↗
PubMed2001

Structural and thermodynamic behavior of eukaryotic initiation factor 4E in supramolecular formation with 4E-binding protein 1 and mRNA cap analogue, studied by spectroscopic methods.

The structural and thermodynamic behavior of the complex formation of eIF4E with either or both mRNA cap analogue (m7GTP, m7GpppA, or m7GpppG) and 4EBP1 has been investigated by spectroscopic measurements. Although the circular dichroism (CD) spectrum of eIF4E was little affected by the association with any cap analogue, the association constant of eIF4E with m7GpppA/G, estimated from the fluorescence quenching, was about 10 times larger than that with m7GTP. The van't Hoff analyses showed that the m7GpppA/G binding is enthalpy-driven with a large negative deltaH(o), and this is in contrast with the entropy-driven binding of m7GTP, where the positive deltaS(o) is large enough to overcome an increase of deltaH(o). This different behavior obviously originates in the interaction of the second nucleotide in m7GpppA with eIF4E, suggesting the importance of the nucleotide sequence linked to the m7Gppp terminal moiety, in addition to the specific interaction with the m7G base, for the recognition of mRNA cap structure by eIF4E. On the other hand, the CD spectra indicated that the binding of 4EBP1, an endogenous eIF4E-regulatory protein without having any defined secondary structure, shifted the m7GTP- or m7GpppA/G-bound eIF4E to an irregular structure, although such a structural change was not observed for eIF4E alone. The association constant of 4EBP1 with m7GTP- or m7GpppA/G-bound eIF4E was by two orders of magnitude larger than that with eIF4E alone. These results suggest the close interrelation in the supramolecular formation of 4EBP-eIF4E-mRNA cap structure.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Difference in the occurrence of cardiovascular events according to class of antihypertensive agent, based on a follow-up study of Japanese hypertension patients.

We conducted a nested case-control study to evaluate the relationship between antihypertensive agent class and the incidence of initial cardiovascular events. A total of 7.443 patients being treated with an antihypertensive agent in 1985-1986 were enrolled for follow-up of up to 5 years. A total of 362 patients (186 males and 176 females) developed cardiovascular events. Age (5-year interval) and sex-matched controls were then randomly selected. A Multiple logistic regression analysis was done to control for the effects of confounding factors. The results showed that the use of diuretics and beta-blockers was associated with a reduced risk of cardiovascular events (odds ratio [OR] =0.65, 95% confidence interval [CI]: 0.49-0.86, and OR=0.75, 95% CI: 0.56-1.02, respectively), against a significantly raised risk associated with the use of calcium antagonists (OR=1.34, 95% CI: 1.03-1.80). However, as far as stroke was concerned, there was no significant association of risk with the use of any agent. The control group was found to be similar to the case group with respect to the changes in the treatment program during the follow-up period. The results suggest that the calcium antagonists used in Japan during the period of 1985-1990 constituted a potential risk for the occurrence of cardiovascular events.

Adrenergic beta-Antagonists↗
PubMed2001

[Strategy for circulatory disturbance].

A meta-analysis by the Cochrane Stroke Group (CSG) showed that thrombolytic therapy increased deaths as well as symptomatic and fatal intracranial hemorrhage within the first seven to 10 days and at final follow-up, although these risks are offset by a reduction in disability in survivors, so that there is overall a significant net reduction in the proportion of patients dead or dependent. Trials testing intravenous (i.v.) tPA suggest that it may be associated with less hazard and more benefit. A recent trial demonstrated that intra-arterial pro-urokinase improved long-term outcome in patients with M 1 or M 2 occlusion within 6 hours of onset. Trials of the third generation of thrombolytic agents are ongoing in patients with acute ischemic stroke. The latest CSG's meta-analysis showed that immediate anticoagulant therapy in patients with acute ischemic stroke was not associated with net short or long-term benefit because there was no evidence that anticoagulant therapy reduced deaths or non-fatal stroke during treatment or patients dead or dependent at the end of follow-up. However, an i.v. low-molecular-weight heparinoid showed a trend toward improving long-term outcome in subgroup of patients with atherothrombotic stroke. The thrombin inhibitor argatroban was proven to be comparable to the thromboxane A2 synthetase inhibitor ozagrel in the effect on the outcome at one month in patients with atherothrombotic stroke within 48 hours of onset in Japan, and a trial of the agent is ongoing in patients with ischemic stroke within 12 hours of onset in the United States. Two large trials of aspirin in patients with ischemic stroke within 48 hours of onset indicated that aspirin had a modest effect on reducing patients dead or dependent at the end of follow-up. An international trial of abciximab, a monoclonal antibody directed against platelet glycoprotein IIb/IIIa, is ongoing in patients with ischemic stroke within 6 hours of onset.

Abciximab↗
PubMed2000

Selected mutations in a mesophilic cytochrome c confer the stability of a thermophilic counterpart.

Mesophilic cytochrome c(551) of Pseudomonas aeruginosa (PA c(551)) became as stable as its thermophilic counterpart, Hydrogenobacter thermophilus cytochrome c(552) (HT c(552)), through only five amino acid substitutions. The five residues, distributed in three spatially separated regions, were selected and mutated with reference to the corresponding residues in HT c(552) through careful structure comparison. Thermodynamic analysis indicated that the stability of the quintuple mutant of PA c(551) could be partly attained through an enthalpic factor. The solution structure of the mutant showed that, as in HT c(552), there were tighter side chain packings in the mutated regions. Furthermore, the mutant had an increased total accessible surface area, resulting in great negative hydration free energy. Our results provide a novel example of protein stabilization in that limited amino acid substitutions can confer the overall stability of a natural highly thermophilic protein upon a mesophilic molecule.

Bacteria↗
PubMed2000

Structural basis of the interaction between IgG and Fcgamma receptors.

The binding of multivalent antigen-antibody complexes to receptors for the Fc portion of IgG (FcgammaR) induces the clustering of the FcgammaR and triggers cell activation leading to defence reactions against pathogens. The Fc portion of IgG consists of two identical polypeptide chains which are related to each other by a 2-fold axis and are folded in two structural domains, the C(H)2 domain, near the flexible hinge region of the IgG molecule, and the C(H)3 domain. We studied the interaction in solution between the Fc fragment of mouse IgG2b and the extracellular region of mouse FcgammaRII. We find that one Fc molecule binds one FcgammaRII molecule only. Using NMR spectroscopy, we show that FcgammaRII binds to a negatively charged area of the C(H)2 domain, corresponding to the lower hinge region, and that the binding of FcgammaRII onto one of the two symmetrically related sites on the Fc induces a conformational change in the other site. We therefore propose a model that explains why IgG molecules are unable to trigger FcgammaR-mediated cellular responses spontaneously in the absence of crosslinking by multivalent antigens.

Animals↗
PubMed2000

Fluorescent oxidation products derived from DBD-thiocarbamoyl amino acid in the modified Edman sequencing analysis.

The fluorescent product obtained by the oxidation of 7-N, N-dimethylaminosulfonyl-4-(2,1,3-benzoxadiazolyl) (DBD)-thiocarbamoyl (TC)-proline with NaNO(2)/H(+) in the modified Edman sequencing procedure was identified as the corresponding thiazolyl compound, N-[(8-dimethylaminosulfonyl)thiazolo[5,4, e]benzo[2,1,3]oxadiazol-5-yl]-L-proline, formed by the attack of the sulfur atom of the thiocarbamoyl group on the benzofurazan skeleton. The reaction mechanism for the formation of the fluorescent compound from DBD-TC primary and secondary amines is also discussed.

Amino Acids↗
PubMed2000

Rapid-growing carcinosarcoma of the esophagus arising from intraepithelial squamous cell carcinoma: report of a case.

A case of carcinosarcoma arising from the intraepithelial spreading area of esophageal squamous cell carcinoma (SCC) is reported herein. A 64-year-old man was referred to our hospital for investigation of a sore throat and dysphagia. An endoscopic examination revealed a 2. 5-cm polypoid mass in the mid-esophagus. Esophagograms taken 1 month prior to consultation by our hospital and just before surgery revealed marked change within a period of less than 2 months from a 2-cm sessile elevated mass to a 4-cm polypoid mass with a lobular appearance. The resected specimen contained two lesions in the esophagus. The larger one measured 4.0 x 2.0 x 2.0 cm and had a pedunculated polypoid shape, while the smaller one, measuring 1 cm in diameter, was a plateau-type elevated lesion located 3 cm distal from the larger mass. Histologically, the distal smaller lesion was diagnosed as primary SCC associated with a high frequency of intraepithelial spread, while the larger polypoid mass was composed of spindle-shaped sarcomatous cells, arising from the intraepithelial spread of SCC. To our knowledge, this is the only reported case of esophageal carcinosarcoma arising from an area of intraepithelial spread of SCC that showed such surprisingly rapid growth.

Carcinoma in Situ↗
PubMed2000

Boomerang deformity of cervical spinal cord migrating between split laminae after laminoplasty.

Patients with cervical compression myelopathy were studied to elucidate the mechanism underlying boomerang deformity, which results from the migration of the cervical spinal cord between split laminae after laminoplasty with median splitting of the spinous processes (boomerang sign). Thirty-nine cases, comprising 25 patients with cervical spondylotic myelopathy, 8 patients with ossification of the posterior longitudinal ligament, and 6 patients with cervical disc herniation with developmental canal stenosis, were examined. The clinical and radiological findings were retrospectively compared between patients with (B group, 8 cases) and without (C group, 31 cases) boomerang sign. Moderate increase of the grade of this deformity resulted in no clinical recovery, although there was no difference in clinical recovery between the two groups. Most boomerang signs developed at the C4/5 and/or C5/6 level, where maximal posterior movement of the spinal cord was achieved. Widths between lateral hinges and between split laminae in the B group were smaller than in the C group. Flatness of the spinal cord in the B group was more severe than in the C group. In conclusion, the boomerang sign was caused by posterior movement of the spinal cord, narrower enlargement of the spinal canal and flatness of the spinal cord.

Adult↗
PubMed2000

Purification, characterization, and molecular cloning of group I phospholipases A2 from the gills of the red sea bream, Pagrus major.

Phospholipase A2 (PLA2) activity was investigated in various tissues of male and female red sea bream. In both male and female fishes, the specific activity of PLA2 in the gills was 70 times higher than that in other tissues, such as the adipose tissue, intestine, and hepatopancreas. Therefore, we tried to purify PLA2 from the gill filaments of red sea bream to near homogeneity by sequential chromatography on Q-Sepharose Fast Flow, Butyl-Cellulofine, and DEAE-Sepharose Fast Flow columns, and by reversed-phase high-performance liquid chromatography. Two minor and one major PLA2, tentatively named G-1, G-2 and G-3 PLA2, were purified, and all showed a single band with an apparent molecular mass of approximately 15 kDa by sodium dodecylsulfate-polyacrylamide gel electrophoresis. The exact molecular mass values of G-1, G-2, and G-3 PLA2 were 14,040, 14,040 and 14,005 Da, respectively. G-1, G-2, and G-3 PLA2 had a Cys 11 and were all identical in N-terminal amino acid sequences from Ala-1 to Glu-56. A full-length cDNA encoding G-3 PLA2 was cloned by reverse transcriptase-polymerase chain reaction and rapid amplification of cDNA ends methods, and G-3 PLA2 was found to be classified to group IB PLA2 from the deduced amino acid sequence. G-1, G-2, and G-3 PLA2 had a pH optimum in an alkaline region at around pH 9-10 and required Ca2+ essentially for enzyme activity, using a mixed-micellar phosphatidylcholine substrate with sodium cholate. These results demonstrate that three group I PLA2, G-1, G-2, and G-3 PLA2, are expressed in the gill filaments of red sea bream.

Adipose Tissue↗
PubMed2000

Interaction of ribosome recycling factor and elongation factor EF-G with E. coli ribosomes studied by the surface plasmon resonance technique.

BACKGROUND: Ribosome recycling factor (RRF), in concert with elongation factor EF-G, is required for disassembly of the post-termination complex of a ribosome after the release of polypeptides. How RRF dissociates the complex has long been puzzling. Crystal structures of RRF molecules have been solved recently and shown to mimic a transfer RNA (tRNA) shape, which prompted us to examine whether RRF binds to the ribosome as tRNA does. RESULTS: The formation of ribosome complexes on the surface-coupled RRF and elongation factor EF-G of Escherichia coli was monitored in real time with a BIACORE 2000 instrument based on the surface plasmon resonance technique. RRF interacted with 70S ribosomes as well as 50S and 30S subunits, although it interacted preferentially with 50S subunits, which was clearly seen under high but physiological ionic conditions. This 50S interaction was diminished by a single amino acid substitutions for Arg132 of RRF, which did not appreciably affect the protein folding but nullified the activity in vivo and in vitro. Moreover, a set of antibiotics that inhibited the RRF-50S interaction were also inhibitory to the polysome breakdown activity of RRF in vitro. The BIACORE technique also worked very well in demonstrating the action of the antibiotics thiostrepton and fusidic acid, which are inhibitory to the RRF function by freezing the pre- and post-translocation intermediates catalysed by EF-G. CONCLUSIONS: These results suggest that the preferential interplay of RRF with the 50S subunit may be of biological significance, probably reflecting the mode of RRF action. The BIACORE technique proved useful for real-time monitoring of the interaction between the ribosome and translation factors, as well as for screening of potential inhibitors for ribosome recycling factor.

Amino Acid Substitution↗
PubMed2000

Kinematics of the proximal interphalangeal joint of the finger after surface replacement.

Nine fresh-frozen normal human cadaveric long fingers were used to compare the kinematics of the proximal interphalangeal joint (PIP) before and after a resurfacing metal-polyethylene prosthetic replacement (Avanta prosthesis, San Diego, CA) using the magnetic Isotrak system (Polhemus Navigational Systems, Colchester, VT). The kinematics of the PIP joint after replacement were similar to that of the normal joint. The maximum angular displacement was 5 degrees for lateral deviation and 9 degrees for rotation during the passive flexion and extension motion. The center of rotation after implant insertion was nearly identical to the center of rotation of the normal joint. This anatomically designed PIP prosthesis has potential to restore normal motion to the finger PIP joint while resisting physiologic out-of-plane forces such as pinch and grasp.

Arthroplasty, Replacement↗
PubMed2000

Limited myogenic response to a single bout of weight-lifting exercise in old rats.

The purpose of the present study was to compare the myogenic response of hindlimb muscles in young (14-20 wk of age) and old (>120 wk of age) rats with a single exhaustive bout of heavy resistance weight lifting. [(3)H]thymidine and [(14)C]leucine labeling were monitored for up to 2 wk after the exercise bout to estimate serial changes in mitotic activity and the level of amino acid uptake and myosin synthesis. Histological, histochemical, and immunohistochemical [anti-5-bromo-2'-deoxyuridine and myogenic determination genes (MyoD)] analyses of whole muscles and analysis of muscle-specific gene expression (MyoD) using Western blotting and RT-PCR were performed. Old rats showed significant muscle atrophy and a lower exercise capacity than young rats. Exercise-induced muscle damage, as assessed in histological sections, and increases in serum creatine kinase activity were evident in both young and old exercised groups. Mitotic activity was increased in young, but not old, rats 2 days after exercise. There was a biphasic increase in [(14)C]leucine uptake during the 14 days postexercise (peaks at 1-4 and 10 days) in young rats: only the first peak was observed in old rats. There was a lower uptake of [(14)C]leucine in the myosin fraction and an impaired expression of MyoD at the protein (immunohistochemistry and Western blotting) and mRNA (RT-PCR) levels in old rats throughout the postexercise period. These results demonstrate a reduced reparative capability of muscle in response to a single bout of exercise in old compared with young rats.

Aging↗
PubMed2000

Deteriorating ischemic stroke in 4 clinical categories classified by the Oxfordshire Community Stroke Project.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the frequency, possible predictive factors, and prognosis of deteriorating ischemic stroke in 4 clinical categories according to the classification of the Oxfordshire Community Stroke Project (OCSP). METHODS: A total of 350 patients with first-ever ischemic stroke who presented within 24 hours of onset were enrolled. Based on the OCSP criteria, cerebral infarctions were divided into the following 4 clinical categories: total anterior circulation infarcts (TACI), partial anterior circulation infarcts (PACI), lacunar infarcts (LACI), and posterior circulation infarcts (POCI). Clinical deterioration was defined as a decrease of >/=1 points in the Canadian Neurological Scale (CNS) (in TACI, PACI, and LACI) or Rankin Scale (RS) (in POCI) during 7 days from the onset. In each clinical category, deteriorating (D) and nondeteriorating (ND) patients were compared in terms of their background characteristics, risk factors, vital signs, laboratory data, and cranial CT at the time of hospitalization. The acute-phase mortality and functional outcome were also compared. RESULTS: The subjects comprised 86 patients (24.6%) with TACI, 63 (18.0%) with PACI, 141 (40.3%) with LACI, and 60 (17.1%) with POCI. Overall, 90 patients (25.7%) deteriorated. The frequency was very high in TACI (41.9%), followed by LACI (26.2%) and POCI (21.7%), whereas it was very low in PACI (6. 3%). There were some clinical variables that differed significantly between D and ND groups. In the patients with TACI, early abnormalities of the cranial CT and significant stenoses in corresponding arteries were more frequent in the D than the ND group. In those with LACI, the CNS and hematocrit were lower in the D than the ND group. In those with POCI, cerebral atrophy was more severe and significant stenoses in vertebrobasilar arteries were more frequent in the D than ND group. The mortality of the D groups of patients with TACI and POCI exceeded 35%, and the functional outcome was worse in the D group than in the ND group of patients with TACI, LACI, and POCI. CONCLUSIONS: The frequency of deterioration in acute ischemic stroke significantly differed among the OCSP subgroups, and deterioration worsened the prognosis. There were some factors that could predict deterioration: early CT findings in TACI, large-artery atherosclerosis in TACI and POCI, and stroke severity in LACI. Further research to find sophisticated radiological and chemical markers appears to be needed.

Acute Disease↗