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Biomedical subjects

A Maeda

Publications and source records attributed to A Maeda.

At least 163 records · Page 9Linked to original sources

Doxorubicin cardiotoxicity: diastolic cardiac myocyte dysfunction as a result of impaired calcium handling in isolated cardiac myocytes.

We examined intracellular calcium transients of isolated single cardiac myocytes from rats with doxorubicin (DOX)-induced cardiomyopathy with simultaneous measurement of cell motion. DOX was administered i.p. to Sprague-Dawley rats at 2.5 mg/kg once a week for 10 weeks. Field-stimulated calcium transients and simultaneous cell motion in single myocytes were measured in the presence or absence of isoproterenol using fura-2/AM. Histopathologic examination revealed slight changes. The time courses of both calcium transients and cell motion were significantly prolonged by DOX. There was a slight but not significant reduction in parameters of contractility in both calcium transients and cell motion. The beta-adrenoceptor responsiveness of both calcium transients and cell motion was not significantly impaired compared with the controls. Our data indicated that, despite the slight histologic changes in the heart in DOX-induced cardiomyopathy, impaired sequestration of intracellular free calcium ions in individual myocytes may be one factor leading to diastolic dysfunction. Monitoring of diastolic function is important to detect early cardiotoxicity caused by DOX.

Animals↗

Solvent-dried and gamma-irradiated tendon allografts in rats. Mechanical and morphological evaluation.

We examined solvent-dried, gamma-irradiated (SD-R) allografts and fresh-frozen (FF) allografts mechanically and morphologically. Before transplantation, FF grafts were more than six times stronger than SD-R grafts. After four weeks, the tensile strength was about the same in both groups. At 24 weeks only collagen fibrils of small diameter were observed in the SD-R grafts while in FF grafts fibrils of small and intermediate diameter were seen. Clinically, we suggest that SD-R grafts could be used as a favourable alternative to FF grafts if care was taken regarding their initial mechanical weakness.

Actin Cytoskeleton↗

Articular cartilage repair. Rabbit experiments with a collagen gel-biomatrix and chondrocytes cultured in it.

To repair a full-thickness articular cartilage defect in rabbit knees, we developed a technique of using a collagen gel hardened by cultured allogeneic chondrocytes in it. The gel-chondrocyte composite accumulated an intense metachromatic matrix, and had elasticity and stiffness enough to be shaped easily after 2 weeks' culture in vitro. It was implanted into full-thickness articular cartilage defects. Histologic evaluation was performed up to 6 months after surgery, using a histologic grading scale composed of 5 categories. In the gel-chondrocyte composite implanted group, good repair was observed from as early as 1 day up to 6 months. On the other hand, in the empty control group, no repair was observed 1 day to 2 weeks after the defects were made. At 4 weeks, some repair occurred, but even at 6 months the repair was not good.

Animals↗

Influence of landing on the supination and pronation in the foot joint.

The purpose of this study was to measure the changes of supination and pronation in the ankle joint at landing to quantify the influence of shock attenuation during landing. The subjects did two different motions, jumping down on the force platform from posterior and lateral views. The rear view of single foot contact in a jump from height of 30 and 60 cm showed a landing on the inside of the rear part of the foot (pronation) followed after about 0.03 sec by a rolling outward of the foot (supination). The variables describing changes in three angles of the ankle joint indicated that the standing position was more sensitive on the pronation and supination during ground contact.

Adult↗

[Successful treatment with donor leukocyte transfusion followed by interferon-alpha in a patient with relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation].

A 44-year-old man with CML in chronic phase was admitted for BMT from an HLA-identical sibling. Ph positive cells were undetectable at 3 and 7 months after BMT but became detectable by cytogenetic analysis of bone marrow aspirates at 12 months after BMT. He was treated with IFN-alpha (6 million units/day, 3 times a week) without apparent effect. Donor leukocyte transfusion (DLT) was performed four times between 20 months and 23 months after BMT, transfusing 3.4 x 10(8) mononuclear cells/kg. However, leukocytosis appeared and the NAP score declined at 25 months after BMT. FISH analysis revealed an increase in bcr-abl positive cells. IFN-alpha was restarted using the same schedule at 26 months after BMT. Three months after restarting IFN-alpha, the leukocyte count fell to the normal range, NAP score increased to a normal level, and bcr-abl positive cells decreased markedly. He has remained in hematological and cytogenetic remission for 20 months, and bcr-abl chimeric mRNA remained undetectable by PCR. These results suggest that CML which does not respond to DLT may be cured by subsequent IFN-alpha therapy, possibly by inducing anti-leukemia immune responses.

Adult↗

[Rapid tapering of cyclosporine for cytogenetic relapse shortly after bone marrow transplantation in a patient with chronic myeloid leukemia].

A 53-year-old female case of cytogenetically relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation (BMT) who achieved remission by withdrawal of immunosuppressant is reported. On day 690 of this presentation she is well and alive with performance status of 100%. She had episodes of cyclic oscillation of her neutrophil count during hydroxyurea therapy lasting 1 year before transplantation. Increase of the neutrophils at the time of BMT might have contributed to her early relapse on day 207. Withdrawal of immunosuppressant was successful at least in this case.

Bone Marrow Transplantation↗

Telomerase activity as a novel marker of lung cancer and immune-associated lung diseases.

Telomerase maintains telomere length and is considered to be necessary for the indefinite proliferation of human cells. Telomerase activity is detected not only in germline and immortal cancer cells, but also in stem/progenitor cells of renewal tissues and activated lymphocytes. While it is generally agreed that telomerase is a useful tumor marker, the utility of telomerase activity in non-cancerous cells should also be considered. In the present study, we quantitatively examined telomerase activity in 56 cytology samples and 106 bronchoalveolar lavage samples obtained from patients with various respiratory diseases. Fourteen of 34 samples obtained from lung cancer patients showed detectable telomerase activity, while only 7 of 128 samples obtained from patients without lung cancer did (p<0.001). Moreover, 12 of 14 telomerase-positive samples with lung cancer showed strong signals, while none without lung cancer did. Among 106 non-cancerous bronchoalveolar lavage samples, 4 telomerase positive samples had increased number of lymphocytes and increased disease progression. These findings indicate that evaluation of telomerase activity may not only be a useful diagnostic test for lung cancer, but may also be a marker of disease aggressiveness for immune-associated lung diseases.

Biomarkers↗

[Aortic valvular vegetation in annuloaortic ectasia due to idiopathic cystic medial necrosis: a case report].

Annuloaortic ectasia is often accompanied by Marfan syndrome and associated with infective endocarditis usually involving the mitral valves. We treated a patient with annuloaortic ectasia due to idiopathic cystic medial necrosis who developed congestive heart failure with aortic valvular vegetation. A 56-year-old man had dyspnea on effort since the beginning of January, 1997 and was admitted to our hospital on April 6, 1997 because of orthopnea. The diagnosis was congestive heart failure due to severe aortic regurgitation with annuloaortic ectasia detected by echocardiography. Medication and rest after hospitalization relieved his symptoms but congestive heart failure deteriorated after he had a high fever. At this time, a vegetation attached to the noncoronary cusp of the aortic valve was found which had not been detected on admission. Blood culture yielded Streptococcus sanguis. The diagnosis was infective endocarditis involving the aortic valve. Surgical correction (Bentall method) improved congestive heart failure and he was discharged on August 4, 1997 without recurrence of endocarditis. Infective endocarditis involving the aortic valves is a possible cause of development or deterioration of congestive heart failure in patients with annuloaortic ectasia.

Aortic Diseases↗

Molecular cloning and characterization of a human brain ryanodine receptor.

We have cloned and sequenced the cDNA of the human brain ryanodine receptor (RyR3), which is composed of 4866 amino acids and shares characteristic structural features with the rabbit RyR3. Northern blot analysis shows that the human RyR3 mRNA is abundantly expressed in hippocampus, caudate nucleus and amygdala as well as in skeletal muscle. The human RyR3 mRNA is also detected in several cell lines derived from human brain tumors. Functional expression of RyR3 and a chimeric RyR suggests that RyR3 forms a calcium-release channel with a very low Ca2+ sensitivity.

Animals↗

A novel Go-mediated phototransduction cascade in scallop visual cells.

Scallop retinas contain ciliary photoreceptor cells that respond to light by hyperpolarization like vertebrate rods and cones, but the response is generated by a different phototransduction cascade from those of rods and cones. To elucidate the cascade, we investigated a visual pigment and a G-protein functioning in the hyperpolarizing cell. Sequencing of cDNAs and in situ hybridization experiments showed that the hyperpolarizing cells express a novel subtype of visual pigment, which showed significant differences in amino acid sequence from other visual pigments. Cloning cDNA genes of G-protein and immunohistochemical analysis revealed the presence of an alpha subunit of a Go type G-protein, 83% identical in amino acid sequence to mammalian Go(alpha) in the nervous system, in the photoreceptive region of the cells. The results demonstrate that a novel, Go-mediated, phototransduction cascade is present in the hyperpolarizing cells. The phototransduction cascade in the scallop hyperpolarizing cell provides an alternative system to investigate Go-mediated transduction pathways in the nervous system. Molecular phylogenetic analysis strongly suggests that the Go-mediated phototransduction system emerged before the divergence of animals into vertebrate and invertebrate in the course of evolution.

Amino Acid Sequence↗

Risk indicators of low back pain among workers in Japan. Association of familial and physical factors with low back pain.

STUDY DESIGN: A questionnaire was given to 3,042 Japanese workers at a factory in 1992. It surveyed age, gender, weight, height, job classification, and work environment, as well as the perceived causes, onset age, and characteristics of low back pain. Family history of low back pain among first-degree relatives and perception of physical condition also were assessed. OBJECTIVES: To investigate the risk indicators of low back pain in Japanese workers with various kinds of job classifications in a manufacturing company. SUMMARY OF BACKGROUND DATA: Risk indicators of low back pain in Japanese patients have not been fully investigated in previous studies. METHODS: Prevalence rates and characteristics of low back pain were examined among 3,042 factory workers (2,517 men and 525 woman) with jobs with varying physical demands. In the analysis of risk indicators of low back pain, the odds ratios and 95% confidence intervals were computed. In addition, a multiple logistic analysis was performed to evaluate risk indicators of low back pain. RESULTS: Point and lifetime prevalence of low back pain were correlated with the physical demands of the job. The perceived cause found to be most associated with low back pain were lifting in workers with jobs requiring moderate to heavy work and sports activity in sedentary workers. Family history of low back pain in parents, siblings, and children was a risk indicator of low back pain. The average age of the first attack of low back pain in workers with a family history of it in their parents was significantly younger than that in workers with no family history in a multiple logistic analysis in male workers, the physical work demands, age, and family history of low back pain in their parents were risk indicators; however, obesity was not a risk indicator. Physical and mental conditions of workers also were associated with low back pain. CONCLUSIONS: The physical job demands show a clear association with the point and lifetime prevalence of low back pain, and improvements in work conditions may decrease low back symptoms among workers. It is likely that a family history of low back pain and physical and mental conditions of workers also should be considered in the management of low back pain.

Adult↗

Water and peptide backbone structure in the active center of bovine rhodopsin.

Difference FTIR spectra in the conversion of rhodopsin or isorhodopsin to bathorhodopsin were recorded for recombinant wild-type and E113Q bovine rhodopsins. Differences in various vibrational modes between E113Q and the wild-type proteins whose Schiff bases interact with chloride and Glu113, respectively, were analyzed. Water molecules in rhodopsin that change upon formation of bathorhodopsin are detected by a change in frequency of the O-H stretching vibration from 3538 to 3525 cm(-1). This change in the wild-type protein is absent in E113Q. One or a few water molecules are therefore suggested to be located in the proximity of Glu113, the counterion of the Schiff base. Another water vibration at 3564 cm(-1), which is shifted to 3542 cm(-1) in bathorhodopsin in the wild type, persists in E113Q but with approximately 5-cm(-1) shift toward higher frequency. This is due to water molecules that may be located at a site somewhat more remote from Glu113. Structural changes of some peptide carbonyls and amides are also absent in E113Q. On the other hand, the E113Q protein shows shifts of the N-H+ stretching vibrational band, that is probably due to the protonated Schiff base, upon conversion of rhodopsin to bathorhodopsin. No corresponding changes were observed in the wild type. We propose a model in which a water molecule interacts with Glu113, the protonated Schiff base, and peptide carbonyls, and amides. These residues undergo structural changes upon formation of bathorhodopsin.

Animals↗

Trp86 --> Phe replacement in bacteriorhodopsin affects a water molecule near Asp85 and light adaptation.

Illumination of the Trp86 --> Phe mutant of bacteriorhodopsin causes anomalous light adaptation, i.e., isomerization of the retinal from all-trans to 13-cis, 15-syn. FTIR spectral analysis shows that illumination at 250 K yields two 13-cis photoproducts, the conventional 13-cis, 15-syn state, BR(C), and another termed BR(X). BR(X) is different from BR(C) because it has a lower N-H in-plane bending frequency and a higher C14-C15 stretching frequency, as well as an absence of coupling between these modes. BR(X), which is stable at 275 K, is more abundant in the photosteady state produced by longer wavelength light and detected as the only photoproduct at 170 K. Its different structural features result from distortion of the C14-C15 bond of the chromophore. In the W86F mutant protein, the small structural changes of a water molecule in the conversion between the all-trans and 13-cis, 15-syn forms and in the formation of the K photointermediate are absent, but the larger changes of water molecule(s) that normally occur in the L and M intermediates are present. We propose that Trp86, together with Asp85, is involved in binding the water molecule and in preventing the formation of the 13-cis, 15-syn photoproducts, BR(C) and BR(X), when the wild type protein is illuminated.

Aspartic Acid↗

Time-resolved fourier transform infrared study of structural changes in the last steps of the photocycles of Glu-204 and Leu-93 mutants of bacteriorhodopsin.

The last intermediate in the photocycle of the light-driven proton pump bacteriorhodopsin is the red-shifted O state. The structure and dynamics of the last step in the photocycle were characterized with time-resolved Fourier transform infrared spectroscopy of the mutants of Glu-204 and Leu-93, which accumulate this intermediate in much larger amounts than the wild type. The results show that E204Q and E204D give distorted all-trans-retinal chromophore like the O intermediate of the wild type. This is simply due to the perturbation of the proton acceptor function of Glu-204 in the O-to-BR transition in the Glu-204 mutants. The corresponding red-shifted intermediates of L93M, L93T, and L93S have a 13-cis chromophore like the N intermediate of the wild type, as reported from analysis of extracted retinal [Delaney, J. K., Schweiger, U., & Subramaniam, S. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 11120-11124]. In spite of their different chromophore structures from the O intermediate, the red-shifted intermediates are similar to the O intermediate but not to the N intermediate of the wild type with respect to structural changes in the peptide carbonyls. The structural changes around Asp-96 in the N intermediate are completely restored also in the red-shifted intermediates of the Leu-93 mutants like in the O intermediate. These results imply that the protein structural changes in the last step proceed regardless of thermal isomerization of the chromophore. Time-resolved Fourier transform infrared spectroscopy with the Glu-204 mutants suggests that the response of Asp-204 (Glu-204 in the wild type) to the protonation of Asp-85 during formation of the M intermediate, which results in proton release, is slow and may occur through structural changes.

Bacteriorhodopsins↗

Structural dynamics of water and the peptide backbone around the Schiff base associated with the light-activated process of octopus rhodopsin.

Difference Fourier transform infrared spectra were recorded for the formation of the photointermediates and isorhodopsin from octopus rhodopsin at low temperatures. Analysis was done for H bonding of the Schiff base, internal water molecules, and the peptide backbone. The imine hydrogen of the Schiff base was in the same H bonding state throughout the photointermediates and the unphotolyzed state. In contrast, H bonding of the hydrogen of the water molecule whose oxygen might be complexed with the imine hydrogen of the Schiff base was altered upon the formation of bathorhodopsin. The same water molecule was in a different H bonding state in the subsequent intermediates, lumirhodopsin and mesorhodopsin. These intermediates were also characterized by a decrease in the C = N bond order of the Schiff base as a reflection of distorted structure around the Schiff base. The polar N-H bond in these intermediates could be also ascribed to the Schiff base. Some changes in H bonding of water and the perturbation of the polyene chain in lumirhodopsin and mesorhodopsin were also observed in isorhodopsin. Acid metarhodopsin exhibited extensive changes in the H bonding states of the peptide backbone and internal water molecules. A large part of these changes was extinguished in alkaline metarhodopsin with the unprotonated Schiff base, suggesting interaction of the protonated Schiff base with the peptide backbone and intramembrane water molecules in acid metarhodopsin.

Animals↗