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Biomedical subjects

T Homma

Publications and source records attributed to T Homma.

At least 19 recordsLinked to original sources

Estimation of photon dose generated by a short pulse high power laser.

The authors obtain a new equation to estimate the forward component of a photon dose generated through the interaction between a target and a short pulse high power laser. As the equation is quite simple, it is useful for calculating the photon dose. The equation shows that the photon dose is proportional to the electron temperature in the range>3 MeV and proportional to the square of the electron temperature in the range<3 MeV. The dose estimated with this method is roughly consistent with the result of Monte Carlo simulation. With some assumptions and corrections, it can reproduce experimental results obtained and the dose result calculated at other laboratories.

Electrons↗

Model testing using data on 137Cs from Chernobyl fallout in the Iput River catchment area of Russia.

Data collected for 10 years following the Chernobyl accident in 1986 have provided a unique opportunity to test the reliability of computer models for contamination of terrestrial and aquatic environments. The Iput River scenario was used by the Dose Reconstruction Working Group of the BIOMASS (Biosphere Modelling and Assessment Methods) programme. The test area was one of the most highly contaminated areas in Russia following the accident, with an average contamination density of 137Cs of 800,000 Bq m-2 and localized contamination up to 1,500,000 Bq m-2, and a variety of countermeasures that were implemented in the test area had to be considered in the modelling exercise. Difficulties encountered during the exercise included averaging of data to account for uneven contamination of the test area, simulating the downward migration and changes in bioavailability of 137Cs in soil, and modelling the effectiveness of countermeasures. The accuracy of model predictions is dependent at least in part on the experience and judgment of the participant in interpretation of input information, selection of parameter values, and treatment of uncertainties.

Cesium Radioisotopes↗

Model testing using data on 131I released from Hanford.

The Hanford test scenario described an accidental release of 131I to the environment from the Hanford Purex Chemical Separations Plant in September 1963. Based on monitoring data collected after the release, this scenario was used by the Dose Reconstruction Working Group of BIOMASS to test models typically used in dose reconstructions. The primary exposure pathway in terms of contribution to human doses was ingestion of contaminated milk and vegetables. Predicted mean doses to the thyroid of reference individuals from ingestion of 131I ranged from 0.0001 to 0.8 mSv. For one location, predicted doses to the thyroids of two children with high milk consumption ranged from 0.006 to 2 mSv. The predicted deposition at any given location varied among participants by a factor of 5-80. The exercise provided an opportunity for comparison of assessment methods and conceptual approaches, testing model predictions against measurements, and identifying the most important contributors to uncertainty in the assessment result. Key factors affecting predictions included the approach to handling incomplete data, interpretation of input information, selection of parameter values, adjustment of models for site-specific conditions, and treatment of uncertainties.

Iodine Radioisotopes↗

Electron acceleration by a nonlinear wakefield generated by ultrashort (23-fs) high-peak-power laser pulses in plasma.

We study experimentally the interaction of the shortest at present (23-fs) , relativistically intense (20-TW), tightly focused laser pulses with underdense plasma. MeV electrons constitute a two-temperature distribution due to different plasma wave-breaking processes at a plasma density of 10(20) cm(-3). These two groups of electrons are shown numerically to constitute bunches with very distinctive time durations.

Journal Article↗

Tea catechin, (-)-epigallocatechin gallate, causes membrane depolarizations of myenteric neurons in the guinea-pig small intestine.

Intracellular recordings were made from enteric neurons in the myenteric plexus of the guinea-pig small intestine to examine actions of one of tea catechins, (-)-epigallocatechin gallate (EGCG), on neuronal activity. EGCG at concentrations from 1 to 20 microM depolarized about 60% of both of S and AH neurons in a concentration-dependent manner, although EGCG-induced depolarizations were largely varied in amplitude from neuron to neuron. The depolarizations started passing off during the presence of EGCG at higher concentrations, and became smaller or almost abolished with repeated applications, indicating the EGCG-induced response shows desensitization-like characteristics. The EGCG-depolarization was associated with a decrease in input membrane resistance, and their reversal potential was estimated about -30 mV. Since the EGCG-depolarization was recorded in the absence of external Ca(2+), it is concluded that one of tea catechins has direct depolarizing effects on a population of myenteric neurons.

Action Potentials↗

Recognition of cell surface GD3 by monoclonal antibody anti-6C2 in rheumatoid arthritis synovial fluid: expression on human T cells with transendothelial migratory activity.

OBJECTIVE: We have previously reported that the anti-6C2 monoclonal antibody (mAb) defines a subset of human CD4+ memory T cells. The present study sought to determine the nature of the 6C2 molecule and the function associated with 6C2+ T cells, and to examine whether this T cell subset is involved in the pathophysiology of rheumatoid arthritis (RA). METHODS: Cytofluorographic analysis was performed for identification of T cell surface molecules displaying a distribution similar to that of the 6C2 molecule. T cells in the synovial fluid of RA patients were examined for expression of the 6C2 molecule. Transendothelial migratory activity was assessed by assay using monolayers of human endothelial cells. Specific reactivity of the anti-6C2 mAb was determined by immunoblotting on gangliosides separated by thin-layer chromatography, and flow cytometric analysis of the cells transfected with complementary DNA (cDNA) was performed for determination of the glycosyltransferases involved in biosynthesis of the gangliosides. RESULTS: On human peripheral T cells, the 6C2 molecule was distributed, by and large, in a pattern similar to that of CDw60, or O-acetyl-GD3. The majority (>70%) of synovial fluid T cells from patients with RA were found to be 6C2 positive, and those 6C2+ T cells exhibited a transendothelial migratory capacity that was inhibited by pretreatment of T cells with anti-6C2 mAb. Moreover, treatment of T cells with neuraminidase resulted in a loss of 6C2 expression as well as a reduction in the transendothelial migratory activity. Anti-6C2 mAb reacted specifically with GD3, but not with O-acetyl-GD3. The reactivity of anti-6C2 mAb was induced on the cell surface only by transfection with cDNA for GD3 synthase. CONCLUSION: The 6C2 molecule is a disialoganglioside, GD3, and is present on a subset of T cells with transendothelial migratory capacity. The 6C2/GD3 molecules, as well as 6C2/GD3+ T cells, appear to play a role in T cell migration and in the inflammation of RA.

Antibodies, Monoclonal↗

Influence of interleukin-10 on the interleukin-1 receptor antagonist/interleukin-1 beta ratio in the colonic mucosa of ulcerative colitis.

A decrease in the ratio of IL-1ra/IL-1 beta produced regionally by the colonic mucosa of patients with ulcerative colitis (UC) is believed to play a role in the pathogenesis of UC. To investigate factors influencing intramucosal IL-1ra/IL-1 beta ratios, we evaluated polymorphism of the IL-1ra gene and the production of mucosal cytokines in Japanese patients with UC. Colonic biopsy specimens of mucosal tissue were placed in organ cultures for 24 h. Then, the supernatant concentrations of IL-1 beta, IL-1ra, IL-8, IL-4, IL-10, and TGF-beta were assayed by ELISA. Genomic DNA was extracted from patient peripheral blood samples, then IL-1ra gene polymorphism was determined using PCR amplification. The mucosa from patients with active stage UC showed a tendency toward a decreased IL-1ra/IL-1 beta ratio. In the resolving stage, IL-1ra/IL-1 beta ratios increased with increasing IL-10 and TGF-beta concentrations. The addition of human recombinant IL-10 to the culture supernatants produced concentration-dependent inhibition of IL-1 beta. In Japanese patients with UC, the IL-1ra allele gene 2 phenotype had no effect on the IL-1ra/IL-1 beta ratio. Our findings suggest that a relative deficiency of IL-10 in patients with UC may contribute to persistent inflammatory changes.

Adult↗

In situ demonstration of angiotensin-dependent and independent pathways for hyperaldosteronism during chronic extracellular fluid volume depletion.

In wild-type mice, 2-wk administration of losartan, an angiotensin (Ang) II type 1 (AT1) receptor antagonist, along with dietary sodium restriction, resulted in an elevation of plasma aldosterone greater than that seen with sodium restriction alone (2.75 +/- 0.35 vs. 1.38 +/- 0.16 ng/ml, P < 0.01). Plasma potassium increased in sodium-restricted, losartan-treated mice (6.0 +/- 0.2 mEq/liter), while potassium remained unchanged in mice with sodium restriction alone. To study the effect of Ang II on glomerulosa cells that may operate independently of plasma potassium in situ, we used chimeric mice made of cells with or without the intact AT1A gene (Agtr1a). When animals were fed a normal diet or chronically infused with Ang II, the aldosterone synthase mRNA was detectable only in Agtr1a+/+ but not Agtr1a-/- zona glomerulosa cells. After 2 wk of sodium restriction, plasma aldosterone increased (1.51 +/- 0.27 ng/ml) and potassium remained on average at 4.5 +/- 0.2 mEq/liter, with aldosterone synthase mRNA expressed intensively in Agtr1a+/+, but not detectable in Agtr1a-/- cells. Simultaneous sodium restriction and losartan treatment caused increases in plasma potassium (5.5 +/- 0.1 mEq/liter) and aldosterone (1.84 +/- 0.38 ng/ml), with both Agtr1a-/- and Agtr1a+/+ cells intensively expressing aldosterone synthase mRNA. Thus, aldosterone production is regulated by Ang II in the adrenal gland during chronic alterations in extracellular fluid volume when plasma potassium is maintained within the normal range. In the light of a previous observation that dietary potassium restriction superimposed on sodium restriction abolished secondary hyperaldosteronism in angiotensinogen null-mutant mice, the present findings demonstrate that when the renin-Ang system is compromised, plasma potassium acts as an effective alternative mechanism for the volume homeostasis through its capacity to induce hyperaldosteronism.

Adrenal Glands↗

[Assessment of physical activities from functional physical fitness tests research for patients with chronic obstructive pulmonary disease].

The purpose of this study was to determine whether the level of physical activity (as measured by 12 functional physical fitness tests) differed between patients with chronic obstructive pulmonary disease (COPD) and normal subjects. Fifty male patients with COPD (70.4 +/- 7.1 yr) and 193 age-matched normal subjects (71.2 +/- 5.2 yr) participated in the study. We administered twelve functional physical fitness tests that were designed to represent muscle strength, muscular endurance, reaction, flexibility, balance, regulation and manipulation. Cardiorespiratory fitness was measured by an incremental, symptom-limited exercise test to the maximal tolerable level on a cycle ergometer, and by the 6-min walk distance. Further, we evaluated what the relationships were between cardiorespiratory fitness and physical activities. The results showed that there were significant differences between COPD and normal groups in cardiorespiratory fitness [peak oxygen uptake (15.7 +/- 4.8 ml/kg/min vs. 23.9 +/- 6.5 ml/kg/min, p < 0.05), peak load (77.9 +/- 33.7 watts vs. 110.3 +/- 37.9 watts, p < 0.05) and 6-min walk distance (466.4 +/- 106.3 m vs. 540.4 +/- 78.3 m, p < 0.05)] and muscular endurance [arm curl (22.6 +/- 5.0 rep/30 s vs. 25.2 +/- 6.0 rep/30 s, p < 0.05), Keeping a half-squat position (32.6 +/- 16.4 s vs. 42.8 +/- 17.7 s, p < 0.05)] and regulation (27.2 +/- 9.4 s vs. 23.3 +/- 5.8 s, p < 0.05) in functional physical fitness test. There were significant correlations between cardiorespiratory fitness, and muscular endurance and regulation. Furthermore, there were significant correlations between FEV1.0 and FEV1.0% pred, and regulation. Therefore, it is important that, besides exercise prescriptions based on the criteria of symptom-limited exercise tests, development of exercise programs based on the level of physical activities may be necessary for patients with COPD.

Aged↗

The effect of Am-80, one of retinoids derivatives on experimental allergic encephalomyelitis in rats.

Experimental allergic encephalomyelitis (EAE) is an autoimmune model with inflammation and demyelination in the central nervous system, which resembles the human demyelinating disorder, multiple sclerosis (MS). In this study, we investigated the effect of Am-80, a synthetic retinoid, on EAE in DA rats. DA rats immunized with complete Freund's adjuvant (CFA) supplemented with myelin basic protein (MBP) developed severe EAE which reached the peak 12 to 14 days after immunization. Am-80 and prednisolone administered orally for 12 days after immunization diminished the clinical symptoms and infiltration of inflammatory cells in a dose dependent manner. However, after stopping administration, EAE recurred in DA rats treated with Am-80, but not with prednisolone. The different responses between Am-80 and prednisolone were not due to the difference in the tolerability to the MBP because both inhibited the delayed-type hypersensitivity response to MBP only during administration. To investigate the mechanism how Am-80 alone delayed the response, the expressional levels of mRNA for interleukin-6 (IL-6), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in spinal cord were examined. Transcriptional levels of IL-6, IFN-gamma and TNF-alpha were parallel with the clinical symptoms of the disease in Am-80-treated rats, that is, expressional levels of their mRNA were diminished during the administration of Am-80, which then increased as soon as the administration was stopped. Among them, the expression of IL-6 mRNA was more rapidly and highly relapsed than that of the other two cytokines mRNA. However, prednisolone attenuated transcriptions of all these cytokines throughout the experiment. Therefore, these findings suggested that the inhibition of EAE is, in part, related to the inhibition of IL-6 production. However, there are many possible mechanism in the suppression of EAE by Am-80, further experiments will be necessary.

Administration, Oral↗

Dual renin gene targeting by Cre-mediated interchromosomal recombination.

This study describes a new approach to targeting clustered genes. Our study began with the establishment of two lines of mice carrying different mutations in either Ren1 or Ren2. These two genes, both encoding renin, span over 40 kb in tandem on chromosome 1. Each gene was mutated by gene targeting to contain loxP sites. These two mutants and Cre transgenic mice were mated to produce offspring carrying the mutant Ren1 and Ren2 genes, as well as the Cre transgene concurrently. Initially, two mutant Ren genes were located on separate chromosomes. Southern analysis of mice from the second generation revealed that the mutant Ren1 and Ren2 were interchromosomally recombined at the loxP sites to produce a new dually mutated allele on the chromosome at the rate of 9.6% (7/73). Thus, interchromosomal recombination can be efficiently programmed by mating as designed using the Cre-loxP system.

Animals↗

CTG triplet repeat expansion in a laryngeal carcinoma from a patient with myotonic dystrophy.

A 66-year-old Japanese man with myotonic dystrophy (DM) underwent total laryngectomy for laryngeal carcinoma. The size of the expanded DNA fragment (EF) from the leukocytes and normal laryngeal tissues of this patient was only slightly longer than that in normal subjects. EF, however, was markedly longer in the laryngeal carcinoma. These findings support the hypothesis that elongation of the CTG repeat in the DM kinase gene occurs during acquired cell proliferation.

Aged↗

Deep-seated segmental neurofibromatosis without café au lait spots.

Segmental neurofibromatosis is a rare disease characterized by neurofibromas with or without café au lait spots localized to one segment of the body. The majority of reported cases have had cutaneous neurofibromas, and patients with deep involvement have rarely been described. We report on two patients with deep-seated segmental plexiform neurofibromatosis and review the literature. All reviewed cases including the present two had no café au lait spots, axillary freckling, Lisch nodules, family history or malignant progression of disease. Differential diagnoses from neuro-fibromatosis 1 (von Recklinghausen disease) and malignant peripheral nerve sheath tumor are important for genetic counseling and avoiding overtreatment.

Adult↗

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↗

A mutation in secY that causes enhanced SecA insertion and impaired late functions in protein translocation.

A cold-sensitive secY mutant (secY125) with an amino acid substitution in the first periplasmic domain causes in vivo retardation of protein export. Inverted membrane vesicles prepared from this mutant were as active as the wild-type membrane vesicles in translocation of a minute amount of radioactive preprotein. The mutant membrane also allowed enhanced insertion of SecA, and this SecA insertion was dependent on the SecD and SecF functions. These and other observations suggested that the early events in translocation, such as SecA-dependent insertion of the signal sequence region, is actually enhanced by the SecY125 alteration. In contrast, since the mutant membrane vesicles had decreased capacity to translocate chemical quantity of pro-OmpA and since they were readily inactivated by pretreatment of the vesicles under the conditions in which a pro-OmpA translocation intermediate once accumulated, the late translocation functions appear to be impaired. We conclude that this periplasmic secY mutation causes unbalanced early and late functions in translocation, compromising the translocase's ability to catalyze multiple rounds of reactions.

Adenosine Triphosphatases↗

Effect of selective IL-6 inhibitor Am-80 on experimental autoimmune encephalomyelitis in DA rats.

AIM: To observe the role of interleukin (IL)-6 in the development of experimental autoimmune encephalomyelitis (EAE). METHODS: DA rats were immunized by injecting bovine myelin basic protein (MBP). mRNA of cytokines, such as IL-6, IL-10, TNF-alpha, TGF-beta 1, IFN-gamma, and iNOS, were detected by RT-PCR. MBP was injected into ear to induce delayed type cutaneous hypersensitivity response (DTH). Histological studies were performed on the spinal cord with HE staining. Nitric oxide (NO) production from cultured murine macrophage clones was stimulated with LPS plus IFN-gamma. RESULTS: DA rats developed EAE disease with a peak of severity on d 13 and d 14. Am-80 (1.0, 3.0 mg/kg), a selective IL-6 inhibitor, inhibited the symptoms in terms of deterioration as observed by the clinical score, body weight and histological findings, in a dose-related manner. A high dose of Am-80 (3.0 mg/kg for 12 d) did not completely inhibit the disease, but delayed the symptoms and enhanced the delayed response. By prolonging the duration of treatment (18 d), Am-80 inhibited the onset of EAE during administration, but the symptoms of EAE appeared after the administration was stopped. Am-80 administerd for 12 d inhibited the DTH response on d 11 but not on d 22. RT-PCR studies demonstrated a strong expression of IFN-gamma, IL-6, IL-10, TGF-beta 1, TNF-alpha, and iNOS mRNA in spinal cord 13 d after immunization. However IFN-gamma, IL-10, TNF-alpha, and iNOS mRNA expression (on d 13) was suppressed by Am-80, except in the case of IL-6, hence the effect of Am-80 on the expression of IL-6 mRNA was examined in additional experiments. After Am-80 was administered for 12 d or 18 d, the expression of IL-6 mRNA was inhibited on d 12 or d 18, but increased on d 13 or d 19, respectively. CONCLUSION: These findings suggest that inhibition of EAE by Am-80 is initiated by inhibition of IL-6 production.

Animals↗