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Biomedical subjects

S Ito

Publications and source records attributed to S Ito.

At least 73 records · Page 4Linked to original sources

Applications of ACORN to data at 1.45 A resolution.

One of the main interests in the molecular biosciences is in understanding structure-function relations and X-ray crystallography plays a major role in this. ACORN can be used as a comprehensive and efficient phasing procedure for the determination of protein structures when atomic resolution data are available. An initial model can automatically be built by ARP/wARP followed by REFMAC for refinement. The alpha helices and beta sheets occurring in many protein structures can be taken as starting fragments for structure solution in ACORN. ACORN, along with ARP/wARP followed by REFMAC, can be an ab initio method for solving protein structure for which data are better than 1.2 A (atomic resolution). Attempts are here made in extending its applications to real data at 1.45 A resolution and also to truncated data at 1.6 A resolution. Two previously known structures, congerin II and alkaline cellulase N257, were resolved using the above approach. Automatic structure solution, phasing and refinement for real data at still lower resolutions for proteins of various complexities are being carried out. Data mining of the secondary structural features using PDB is being carried out for this new approach for 'seed-phasing' to ACORN.

Algorithms↗

Injury of the anterior longitudinal ligament during whiplash simulation.

Anterior longitudinal ligament (ALL) injuries following whiplash have been documented both in vivo and in vitro; however, ALL strains during the whiplash trauma remain unknown. A new in vitro whiplash model and a bench-top trauma sled were used in an incremental trauma protocol to simulate whiplash at 3.5, 5, 6.5 and 8 g accelerations, and peak ALL strains were determined for each trauma. Following the final trauma, the ALLs were inspected and classified as uninjured, partially injured or completely injured. Peak strain, peak intervertebral extension and increases in flexibility parameters were compared among the three injury classification groups. Peak ALL strains were largest in the lower cervical spine, and increased with impact acceleration, reaching a maximum of 29.3% at C6-C7 at 8 g. Significant increases ( P<0.05) over the physiological strain limits first occurred at C4-C5 during the 3.5 g trauma and spread to lower intervertebral levels as impact severity increased. The complete ligament injuries were associated with greater increases in ALL strain, intervertebral extension, and flexibility parameters than were observed at uninjured intervertebral levels ( P<0.05).

Aged↗

The neuromelanin of human substantia nigra: structure, synthesis and molecular behaviour.

The pigmented neurons of the substantia nigra (SN) are typically lost in Parkinson's disease: however the possible relationship between neuronal vulnerability and the presence of neuromelanin (NM) has not been elucidated. Early histological studies revealed the presence of increasing amounts of NM in the SN with aging in higher mammals, showed that NM granules are surrounded by membrane, and comparatively evaluated the pigmentation of SN in different animal species. Histochemical studies showed the association of NM with lipofuscins. However, systematic investigations of NM structure, synthesis and molecular interactions have been undertaken only during the last decade. In these latter studies, NM was identified as a genuine melanin with a strong chelating ability for iron and affinity for compounds such as lipids, pesticides, and MPP+. The affinity of NM for a variety of inorganic and organic toxins is consistent with a postulated protective function for NM. Moreover, the neuronal accumulation of NM during aging, and the link between its synthesis and high cytosolic concentration of catechols suggests a protective role. However, its putative neuroprotective effects could be quenched in conditions of toxin overload.

Aging↗

Epstein-Barr virus nuclear antigen-1 colocalizes with lamin B1 in the nucleoplasm and along the nuclear rim.

Epstein-Barr virus nuclear antigen 1 (EBNA-1) is essential for the maintenance of latent EBV plasmids, and is also a transcriptional regulator. Nuclear lamins, components of the nuclear lamina, have also been found in the nucleoplasm. We report here that EBNA-1 coincided with lamin B1 in the nucleoplasm and around the nuclear rim during S-phase by confocal microscopy of cells transfected with EBNA-1 in the absence of EBV plasmids. Lamin B1, which is rarely detected in nuclear soluble fractions, was detected in chromatin and nuclear matrix fractions of the EBNA-1-expressing cells. These observations suggest that EBNA-1 colocalizes with lamin B1 in the subnuclear sites.

Animals↗

A case of dermatomyositis complicated with pneumomediastinum successfully treated with cyclosporin A.

We describe a rare case of a 46-year-old Japanese man with dermatomyositis (DM) and interstitial lung disease who developed spontaneous pneumomediastinum and subcutaneous emphysema. Relatively mild myositis, mild elevation of CK values and the absence of anti-Jo-1 antibody were observed and the case was similar to amyopathic DM. Treatment of this patient with oral prednisolone and cyclosporin A (CsA) was effective for the myositis and interstitial lung disease. The administration of CsA enabled rapid tapering of the dose of prednisolone without aggravating the disease. Pneumomediastinum and subcutaneous emphysema disappeared 5 months later without recurrence. The serum levels of KL-6 were monitored every 2 weeks to help determine whether this may have contributed to the recurrence of interstitial pneumonitis. This is a rare case of pneumomediastinum in a patient with DM.

Administration, Oral↗

Basic study of an agent for reinforcement of near-infrared fluorescence on tumor tissue.

BACKGROUND AND AIMS: An indocyanine green derivative (ICG-sulfo-OSu) and agents for reinforcement of infrared fluorescence, which can be used as an infrared fluorescent labeling substance suitable for detection of microlesions by an IR fluorescence endoscope, have been developed. The study aims were to confirm the ability of a reinforcement agent, as well as imaging processing, to intensify fluorescence from the labeled antibody on immunohistochemical staining. SUBJECTS AND METHODS: ICG-sulfo-OSu-labeled MUC1 antibody and an IR fluorescence imaging system were employed in the present study. Paraffin sections of gastric cancer were stained with anti-MUC1 antibody by the avidin-biotinylated peroxidase complex method. Among the positive specimens, three cases were used for IR imaging analysis. Octylglucoside was used as a reinforcement agent. RESULTS: The incubation of paraffin sections with ICG-sulfo-OSu-labeled MUC1 antibody resulted in positive staining of the tumor sites by an IR fluorescence imaging system, and the intensity of fluorescence was increased depending on the concentration of octylglucoside and grade of imaging processing. CONCLUSION: A reinforcement agent, and image processing, intensify a labeled antibody excitable by infrared fluorescence in tumor sections and can generate a strong enough fluorescent signal to detect small cancers when examined with an infrared fluorescence endoscope.

Adenocarcinoma↗

Rate constants for the first two chemical steps of eumelanogenesis.

The kinetics of the initial cyclization and redox exchange reactions involved in the eumelanogenic pathway have been studied previously but because of the difficulty of detecting the intermediate cyclodopa by optical means (because its absorbance is in the same range as dopa which is present in excess in the experimental system) no accurate value for the redox exchange reaction has so far been obtained and there is no available analytical methodology that can be applied to the successive first- and second-order reactions involved. We have synthesized cyclodopa and examined the kinetics of the formation of dopachrome following the pulse radiolytic generation of dopaquinone in its presence. From this direct measurement we determined that the rate constant of the reaction between cyclodopa and dopaquinone is 5.3 x 10(6)/M/s. Employing this value in a computational model of the combined cyclization and redox exchange reactions we calculate that the observed kinetics of dopaquinone decay and dopachrome formation are compatible with a cyclization rate constant of 3.8/s.

Benzoquinones↗

Eumelanin and phaeomelanin contents of depigmented and repigmented skin in vitiligo patients.

BACKGROUND: There are two chemically distinct types of melanin: the red-yellow phaeomelanin and the brown-black eumelanin. Both types of melanin have been detected in human hair, epidermis and cultured melanocytes. OBJECTIVES: In a preliminary study, to quantify levels of both eumelanin and phaeomelanin in depigmented as well as repigmented patches of vitiligo following psoralen plus ultraviolet A (PUVA) therapy. METHODS: We enrolled five patients with vitiligo for this study. We took biopsies from depigmented as well as repigmented lesions after PUVA therapy. The eumelanin and phaeomelanin contents of the skin biopsies were quantified by high-performance liquid chromatography. RESULTS: The mean concentrations in depigmented lesions were 229.4 ng per piece for phaeomelanin and 572 ng per piece for eumelanin (mean phaeomelanin/eumelanin ratio 0.36). In repigmented lesions, the mean concentration of phaeomelanin was 74.8 ng per piece and that of eumelanin was 1657.6 ng per piece (mean phaeomelanin/eumelanin ratio 0.049). CONCLUSIONS: Depigmented lesions showed both types of melanin, and contained a substantial amount of phaeomelanin, whereas repigmented lesions after PUVA showed predominantly eumelanin. We detected melanin in depigmented lesions of vitiligo of 5 years duration, suggesting that some residual melanocytes are still active in depigmented lesions.

Adult↗

Amino acid, mineral and vitamin levels in hydrous faeces obtained from coprophagy-prevented rats.

Amino acid, mineral and vitamin levels in hydrous faeces obtained from coprophagy-prevented rats were examined. Two experiments were conducted with rats of different age, 4 weeks and 10 weeks. Six rats each were fed under coprophagy-prevented and coprophagy-allowed (conventional feeding) conditions, respectively. In the first experiment using 4-week-old rats, amino acid values were determined for hydrous faeces and usual faeces obtained in the above-mentioned conditions. In the second experiment using 10-week-old rats, mineral values were determined for both types of faeces. Vitamin values were determined in both experiments. In a comparison of amino acid values and their patterns, specific kinds of amino acids in hydrous faeces were not recognized as growth factors. Sodium and potassium levels in hydrous faeces were significantly higher than those for usual faeces, but those levels were 1/(18-20) of those derived from feed. Although cyanocobalamin and folic acid levels in hydrous faeces were two to three times higher than those for usual faeces, folic acid supplements from coprophagy were 1/8 of those derived from feed. Cyanocobalamin supplements from hydrous faeces were five times larger than those from feed. Therefore, it appears that cyanocobalamin was supplied by the ingestion of hydrous faeces and that this cyanocobalamin supports conventional growth in rats.

Amino Acids↗

Successful perioperative blood purification therapy in patients with maintenance hemodialysis therapy who underwent living donor liver transplantation.

Living donor liver transplantation (LDLT) is a treatment for end-stage liver failure, and was developed to overcome the distinct insufficiency of cadaveric donors. Case 1 is a 56-year-old man who had undergone maintenance hemodialysis therapy for 4 years. An LDLT was performed for the treatment of advanced liver cirrhosis and hepatocellular carcinoma. Continuous hemodiafiltration (CHDF) was performed from the 2nd to 5th days after the operation. Case 2 is a 55-year-old man with primary amyloidosis and chronic renal failure. An LDLT was performed for the treatment of severe abdominal distention caused by a large liver volume. Although CHDF was started at the 3rd day after the operation, it was discontinued within 24 hours because of an increased urinary volume. CHDF was required again from the 6th-8th days, after which the blood purification mode was switched to regular intermittent hemodialysis. Meanwhile, no major problems occurred in either case. In conclusion, CHDF was required for about 5 days from the 2nd day after the operation. The application of careful and aggressive blood purification therapy during the perioperative period is a key to successful LDLT in dialysis patients.

Hemodiafiltration↗

Combined minimally invasive procedure for descending thoracic aortic aneurysm with left main coronary artery disease.

A 78-year-old man had a descending thoracic aortic aneurysm with left main coronary artery disease. Combined beating heart coronary artery bypass and endovascular thoracic aortic aneurysm repair was performed without cardiopulmonary bypass. The left anterior descending artery and the obtuse marginal branch of the left circumflex artery were revascularized through a left antero-lateral small thoracotomy. The aneurysm was excluded with stent grafts through a small femoral incision. This combined less invasive procedure is a promising approach providing better surgical results in patients with thoracic aortic aneurysm and severe coronary artery disease.

Aged↗

In vivo muscle fibre behaviour during counter-movement exercise in humans reveals a significant role for tendon elasticity.

Six men performed a single ankle plantar flexion exercise in the supine position with the maximal effort with counter movement (CM, plantar flexion preceded by dorsiflexion) and without counter movement (NoCM, plantar flexion only) produced by a sliding table that controlled applied load to the ankle (40 % of the maximal voluntary force). The reaction force at the foot and ankle joint angle were measured using a force plate and a goniometer, respectively. From real-time ultrasonography of the gastrocnemius medialis muscle during the movement, the fascicle length was determined. The estimated peak force, average power, and work at the Achilles' tendon during the plantar flexion phase in CM were significantly greater than those in NoCM. In CM, in the dorsiflexion phase, fascicle length initially increased with little electromyographic activity, then remained constant while the whole muscle-tendon unit lengthened, before decreasing in the final plantar flexion phase. In NoCM, fascicle length decreased throughout the movement and the fascicle length at the onset of movement was longer than that of the corresponding phase in CM. It was concluded that during CM muscle fibres optimally work almost isometrically, by leaving the task of storing and releasing elastic energy for enhancing exercise performance to the tendon.

Adult↗

MR detection of iliac bone marrow involvement by malignant lymphoma with various MR sequences including diffusion-weighted echo-planar imaging.

OBJECTIVE: To assess the diagnostic accuracy of MR imaging for detecting bone marrow infiltration by malignant lymphoma. PATIENTS AND DESIGN: Fifty-three patients with malignant lymphoma underwent MR imaging and bone marrow biopsy. In 80 iliac crests of the 53 patients (13 positive specimens in 9 patients and 67 negative specimens in 44 patients), biopsy results and the signal intensity characteristics were compared. MR sequences included T1-weighted SE, T2-weighted FSE with fat suppression, FSE STIR, and diffusion-weighted EPI with fat suppression at 1.5 T. RESULTS AND CONCLUSIONS: To detect lymphoma infiltration, T1-weighted SE had the highest sensitivity (92%) and diffusion-weighted EPI with fat suppression and FSE STIR had the highest specificity (92.5% and 92%, respectively). A combination of T1-weighted SE and FSE STIR yielded the highest sensitivity and specificity (85% and 97%, respectively). A combination of T1-weighted SE and FSE STIR sequences seems to be the current choice of imaging protocol for detecting bone marrow infiltration by malignant lymphoma.

Biopsy↗

Neurons associated with behavioral context errors in the primary and higher-order gustatory cortices in the monkey.

Cue responses of neurons in the taste-related cortex of Japanese macaque monkeys were studied during a NaCl-water discrimination GO-NOGO task, to compare the correct and incorrect responses. Most neurons produced a steady pattern of discharges in response to a given cue at both correct and incorrect responses, presumably responding to the physicochemical nature of the cue. Some neurons showed the discharge pattern for a certain cue changing to that for another cue at task error, presumably representing the subsequent behavioral reaction or behavioral context. These neurons were mainly located in the precentral operculum and orbitofrontal cortex, and rarely in the primary gustatory area, area G.

Action Potentials↗

The neuromelanin of human substantia nigra and its interaction with metals.

Neuromelanin (NM) is a peculiar biochemical component of several neurons in the Substantia Nigra (SN), the target area of the degenerative process in Parkinson Disease (PD). SN NM has peculiarities as to its composition and an impressive capacity of chelating metals, iron in particular, but not exclusively. Gaining insights into the structural and functional characteristics of NM should help understanding the reasons of selective vulnerability of nigral neurons in many parkinsonian conditions. From the present data a protective role of NM can be postulated until the buffering capability toward heavy metals are exhausted. The overloading of NM with iron and other metals in neurons may trigger inflammatory and degenerative processes aggravating the underlying pathological condition.

Drug Interactions↗

A genome-wide linkage analysis of orchard grass-sensitive childhood seasonal allergic rhinitis in Japanese families.

Seasonal allergic rhinitis (SAR) is an inflammatory disease of the nose and eyes that follows sensitization to air-born pollens. We conducted a genome-wide linkage screening of 48 Japanese families (188 members) with orchard grass (OG)-sensitive SAR children (67 affected sib-pairs) in a farming community in central Japan where OG was planted for apple farming and OG pollen is a major cause of SAR. We used the GENEHUNTER program to performed nonparametric multipoint linkage analysis for OG-sensitive SAR as a qualitative trait and for log total serum IgE levels and OG-RAST IgE levels as quantitative traits. Genotyping data of 400 microsatellite markers suggested linkage of SAR to chromosomes 1p36.2, 4q13.3, and 9q34.3 (P < 0.001), linkage of serum total IgE levels to 3p24.1, 5q33.1, 12p13.1, and 12q24.2 (P < 0.001), and linkage of OG-RAST IgE levels to 4p16.1, 11q14.3, and 16p12.3 (P < 0.001). Weak evidence for linkage of SAR to 5q33.1 was also observed (P = 0.01). All these regions, with the exception of 9q34.3, have been previously reported to be linked to asthma and/or atopy. These data suggest that, although loci linked to SAR are likely to be common to asthma, a strong contribution by specific gene(s) to OG-sensitive SAR is unlikely.

Adolescent↗