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Biomedical subjects

Y Sano

Publications and source records attributed to Y Sano.

At least 73 records · Page 4Linked to original sources

Helium flux from a sedimentary basin.

The tritium-3He ages of groundwaters collected from the Saijo Basin in Japan were measured. The ages vary between 11.7 and 16.3 years. The 4He flux of >3 x 10(4) atoms/cm2 s is calculated by the 4He concentrations and ages. In addition the helium flux of 8.3 x 10(5) atoms/cm2 s is calculated at the Higashi-Niigata gas field in Japan. The above two estimates are consistent with the continental helium flux reported in the literature, suggesting that helium flux on the Earth's crust is uniform.

Geologic Sediments↗

Eotaxin in induced sputum of asthmatics: relationship with eosinophils and eosinophil cationic protein in sputum.

BACKGROUND: Eosinophilic inflammation is a crucial aspect of allergic diseases such as bronchial asthma. An eosinophil-active chemokine, eotaxin, may play a role in the pathogenesis of the tissue eosinophilia accompanying asthma. METHODS: Induced sputa were obtained from 53 patients with atopic asthma and six healthy subjects, and the concentration of eotaxin in the sputum was measured by ELISA. We investigated whether the sputum content of eotaxin is related to 1) asthma status or corticosteroid therapy, and 2) other sputum indices, including percentage of eosinophils and concentration of eosinophil cationic protein (ECP). RESULTS: The patients with stable or unstable asthma showed significantly higher concentrations of sputum eotaxin than the normal controls. The level of sputum eotaxin demonstrated a positive correlation with the percentage of eosinophils in stable asthmatics not receiving corticosteroid therapy, but not in stable patients treated with corticosteroids, or in unstable patients. Sputum eotaxin demonstrated a positive correlation with ECP in asthmatic patients who were either in a stable state or not receiving steroid therapy. CONCLUSIONS: The elevated level of eotaxin detected in association with increased eosinophils and ECP in the sputum of asthmatics suggests that eotaxin is involved in the pathogenesis of eosinophilic airway inflammation. The relationship of eotaxin to airway eosinophilia may be modified by the stability status of asthma and corticosteroid therapy.

Adult↗

Expanded polyglutamine stretches interact with TAFII130, interfering with CREB-dependent transcription.

At least eight inherited neurodegenerative diseases are caused by expanded CAG repeats encoding polyglutamine (polyQ) stretches. Although cytotoxicities of expanded polyQ stretches are implicated, the molecular mechanisms of neurodegeneration remain unclear. We found that expanded polyQ stretches preferentially bind to TAFII130, a coactivator involved in cAMP-responsive element binding protein (CREB)-dependent transcriptional activation, and strongly suppress CREB-dependent transcriptional activation. The suppression of CREB-dependent transcription and the cell death induced by polyQ stretches were restored by the co-expression of TAFII130. Our results indicate that interference of transcription by the binding of TAFII130 with expanded polyQ stretches is involved in the pathogenetic mechanisms underlying neurodegeneration.

Aged↗

Analysis of K-ras codon 12 mutations and p53 overexpression in colorectal nodule-aggregating tumors.

BACKGROUND AND AIMS: Morphologically, colorectal nodule-aggregating tumors are quite different from polypoid-type colorectal tumors that develop via the adenoma-carcinoma sequence. Although polypoid-type colorectal tumors are well known to have a high incidence of K-ras gene mutation and p53 overexpression, colorectal nodule-aggregating tumors have not been examined in terms of genetic changes and clinicopathological features. In the present study, therefore, we analysed the clinicopathological features, genetic changes in K-ras codon 12, and p53 overexpression in colorectal nodule-aggregating tumors. METHODS: A total of 18 colorectal nodule-aggregating tumors were surgically resected and then analysed clinicopathologically. Immunohistochemistry and polymerase chain reaction-single stranded conformational polymorphism were performed to analyse p53 abnormalities in the tumors. K-ras codon 12 mutations were screened out by the polymerase chain reaction-restriction fragment length polymorphism method and analysed by fluorescence direct sequencing. RESULTS: p53 overexpression was observed in six lesions (33%). p53-overexpressing cells were observed in parts of carcinoma or adenoma showing high-grade atypia. Four of the 10 (40%) samples had a p53 gene mutation. Nine of the 18 (50%) samples had a K-ras codon 12 point mutation. In eight cases (89%), the mutations of the K-ras codon 12 were of the same type: GGT (glycine) to GTT (valine). CONCLUSIONS: The colorectal nodule-aggregating tumor has distinctive characteristics showing a morphological phenotype of the superficial-type tumors and genotype of the polypoid tumors in terms of K-ras gene mutation and p53 overexpression.

Adenoma↗

The effect of the membrane fluidity on pharmacokinetics for lipid A analog E5531.

The effect of the dispersing procedure on the aggregate size, membrane fluidity and the pharmacokinetics were evaluated for the lipid A analog E5531. The size of the aggregates prepared by the pH-jump method (pH 11.0-->7.3) was decreased, reaching 20 nm with increasing dispersing time in 0.003 N NaOH (pH 11.0). The membrane fluidity of the aggregates increased with increasing dispersing time. When prepared by the normal dilution method (pH 7.3-->7.3), the size of the aggregates remained constant at 150 nm and the membrane fluidity was smaller compared to samples prepared by the pH-jump method. Using samples with different degrees of hydration and different membrane fluidities prepared by the pH-jump method, the pharmacokinetics after intravenous administration into rats were evaluated, and the data obtained confirmed that the membrane fluidity was correlated with the pharmacokinetics in rat. In addition, E5531 vials were stable for 24 months at room temperature when used within 24 hr after reconstitution.

Animals↗

Neural control of ocular immune privilege.

Ocular immune privilege arises from interactions between the immune apparatus and the eye itself, thereby providing immune protection for the eye that is devoid of sight-threatening inflammation. On the one hand, antigens injected intraocularly elicit deviant systemic immune responses that are devoid of immunogenic inflammation (Anterior Chamber-Associated Immune Deviation, ACAID). On the other hand, the ocular microenvironment (aqueous humor, secreted by cells that surround this chamber) suppresses intraocular expression of immunogenic inflammation. Several lines of evidence indicate that ocular immune privilege is under neural control. First, aqueous humor contains neuropeptides (alpha-MSH, VIP, CGRP) that inhibit and alter the functional properties of T lymphocytes and macrophages. Second, when corneal nerves are severed, the tissues surrounding the anterior chamber cease secreting immunosuppressive factors and ACAID fails--until the nerves regrow. Third, light deprivation abolishes the capacity of the anterior chamber to support ACAID induction, a process that is sensitive to neuropeptides and melatonin. The photoreceptor(s) responsible for ACAID are connected to the nervous system and may reside in the anterior segment and/or the retina. Thus, neural elements from the central nervous system and within the eye help to shape both the induction and the expression of ocular immunity, thereby promoting immune privilege.

Animals↗

Analysis of intragenic recombination at wx in rice: correlation between the molecular and genetic maps within the locus.

In plant genomes as well as other eukaryotic genomes, meiotic recombination does not occur uniformly. At the level of the gene, high recombination frequencies are often observed within genetic loci in maize, but this feature of intragenic recombination is not seen at the csr1 locus in Arabidopsis. These observations suggest that meiotic recombination in plant genomes varies considerably among species. In the present study we investigated meiotic recombination at the wx locus in rice. The mutation sites of wx mutants induced by ethyl methanesulfonate (EMS) treatment or gamma-ray irradiation and a spontaneous wx mutant were physically characterized, and the genetic distances between those wx mutation sites were estimated by pollen analysis. Based on these results, the recombination frequency at the wx locus in rice was estimated as 27.3 kb/cM, which was about 10 times higher than the average for the genome, suggesting that there was a radically different rate of meiotic recombination for intra- and intergenic regions in the rice genome.

Alleles↗

The effect of divalent cations on the membrane properties and pharmacokinetics in rat of the lipid A analogue E5531.

To obtain information on the effects of Ca2+ on the membrane properties of the lipid A analogue E5531, we have determined the aggregate size, zeta potential, membrane fluidity, micropolarity and permeability of the E5531 membrane as a function of Ca2+ levels. Within the molar ratios of [Ca2+]/[E5531] = 1 and 3, Ca2+ increased the zeta potential of the E5531 membrane but had no effect on aggregate size (approximately 20 nm). Within the above ratios, Ca2+ decreased the membrane fluidity, as measured by micropolarity of E5531 and increased the phase transition temperature. The pharmacokinetics in rats for these samples with different membrane fluidity, prepared by changing the pre-dose formulation concentration of Ca2+, was determined and a correlation between membrane fluidity and pharmacokinetics was clearly observed. It thus appears that Ca2+ effects the membrane fluidity of E5531 as well as its pharmacokinetics in rats.

Animals↗

Large-scale cDNA analysis reveals phased gene expression patterns during preimplantation mouse development.

Little is known about gene action in the preimplantation events that initiate mammalian development. Based on cDNA collections made from each stage from egg to blastocyst, 25438 3'-ESTs were derived, and represent 9718 genes, half of them novel. Thus, a considerable fraction of mammalian genes is dedicated to embryonic expression. This study reveals profound changes in gene expression that include the transient induction of transcripts at each stage. These results raise the possibility that development is driven by the action of a series of stage-specific expressed genes. The new genes, 798 of them placed on the mouse genetic map, provide entry points for analyses of human and mouse developmental disorders.

Animals↗

Comparison of Waxy gene regulation in the endosperm and pollen in Oryza sativa L.

The Waxy (Wx) gene controls amylose synthesis in rice (Oryza sativa) and its expression is regulated organ-specifically. The Wx gene is expressed in the endosperm and pollen but not in other organs. In order to know whether Wx gene regulation is the same in the endosperm and pollen, we compared expression patterns of the rice Wx gene in these two organs by immunoblot analysis. We focused on the allelic differences (Wxa and Wxb), cool temperature response and effects of the mutation at the du loci. The results obtained are as follows. First, the quantitative regulation depending on two alleles, Wxa and Wxb, was common to both organs; Wx protein levels from the Wxa allele were about 10-fold higher than those from the Wxb allele in the pollen as well as in the endosperm. Second, in both the endosperm and pollen, expression of the Wxb gene, but not the Wxa gene, was enhanced in response to cool temperature. In contrast to these two types of regulation, analysis of two du mutants, 2035 (du1) and 76-3 (du2), revealed that the pattern of reduction in Wx protein levels in the pollen was distinct from that in the endosperm, suggesting that functions of the two du+ genes differ in these two organs.

Alleles↗

Soluble Fas ligand expression in the ocular fluids of uveitis patients.

PURPOSE: The expression of Fas ligand (FasL) in ocular tissues is thought to play a critical role in maintaining immune privilege in the eye. In this study, to clarify the involvement of the Fas-FasL system in inflammatory processes of the eye,we examined soluble FasL (sFasL) in ocular inflammation. METHODS: Using ELISA systems recently developed, sFasL concentrations in aqueous humor (AH) and/or vitreous fluid (VF) were measured. AH was obtained from 17 eyes of 17 uveitis patients and from 12 eyes of 12 non-uveitis (cataract) patients. VF was obtained from 22 eyes of 22 uveitis patients and 7 eyes of 7 non-uveitis (macular hole) patients. Serum levels of sFasL were also determined. RESULTS: sFasL in AH and VF was below the detection limit of the ELISA systems in all non-uveitis eyes. On the other hand, sFasL was detected in AH from uveitis patients where it measured 367.0 +/- 154.7 pg/ml (mean +/- SEM). sFasL was also detected in VF from uveitis patients where it measured 1132.2 +/- 281.7 pg/ml. None of the sera from patients with or without uveitis contained a detectable level of sFas L. CONCLUSIONS: sFasL levels in AH and VF are elevated in the eye during ocular inflammation. Fas-FasL mediated apoptosis may play an important role in the regulation of inflammation during uveitis.

Aged↗

Regulatory effects of 1alpha,25-dihydroxyvitamin D(3) on cytokine production by human corneal epithelial cells.

PURPOSE: The topical administration of 1alpha,25-dihydroxy-vitamin D(3) [1alpha,25(OH)(2)D(3) ] inhibits Langerhans cell (LC) migration and corneal neovascularization in mice. Since the cytokines that induce LC migration [e.g. interleukin-1 (IL-1)] and corneal neovascularization [e.g. interleukin-8 (IL-8)] are produced by human corneal epithelial cells, we investigated the inhibitory effects of 1alpha,25(OH)(2)D( 3) on cytokine production by these cells in vitro. METHODS: In this experiment, human corneal epithelial cells, cultured in DMEM-FBS until confluence, were then switched to serum-free DMEM containing insulin, transferrin, and sodium selenite (DMEM-ITS) for 48 hours. Next, they were cultured with DMEM-ITS containing 1alpha,25(OH)(2)D(3 ) at concentrations of 10(-7) M, 10(-11) M, or 10( -15) M, and vehicle only (0.1% ethanol). After 6 or 12 hours in this culture, the supernatants were collected and concentrations of IL-1alpha, IL-1b, and IL-8 were quantified by ELISA. RESULTS: Significantly lower levels of IL-1alpha and IL-1b were detected in supernatants from cells cultured with 1alpha, 25(OH)(2)D( 3) (10(-7) M, 10(-11) M, and 10(-15) M), compared to cells cultured with vehicle only. This was true at 6 and 12 hours after the addition of 1alpha,25(OH)(2)D(3) (p < 0.05). IL-8 production inhibition by 1alpha,25(OH)(2)D(3), on the other hand, was detected at 6 hours (p < 0.0005) but not at 12 hours (p> 0.1). CONCLUSIONS: 1alpha,25(OH)(2)D(3) inhibits cytokine (IL-1alpha, IL-1b, and IL-8) production by human corneal epithelial cells in vitro. We suspect that 1alpha,25(OH)(2)D(3) can inhibit LC migration and corneal neovascularization, as is seen in ocular surface inflammation.

Calcitriol↗

Effects of 1alpha,25-dihydroxyvitamin D3 on Langerhans cell migration and corneal neovascularization in mice.

PURPOSE: To examine the effects of 1alpha,25-dihydroxyvitamin D3 (1alpha,25[OH]2D3), a hormone that has immunosuppressive properties, on Langerhans cell (LC) migration and corneal neovascularization in mouse corneas. METHODS: Two 10-0 nylon interrupted sutures were placed in the center of 50 BALB/c mouse corneas to induce LC migration and corneal neovascularization. The mice were then randomly assigned to one of five groups. Three groups (n = 11, n = 11, n = 6) received topical 1alpha,25(OH)2D3 (at concentrations of 10(-7) M, 10(-)8 M, 10(-9) M), one group (n = 11) received vehicle only, and one group (n = 11) received no eye drops. Instillation (three times a day) began on the first day after suturing. Corneal neovascularization was assessed by slit lamp microscopy and scored according to the length of newly formed corneal vessels. Fourteen days after suturing, the number of LCs that had migrated into the central corneal epithelium was counted by an immunofluorescence assay using an anti-Ia antibody. RESULTS: The number of LCs in the central cornea was 21.9 +/- 2.8 cells/mm2 in the nontreated group and 17.8 +/- 3.9 cells/mm2 in the vehicle-only group. Significantly fewer LCs were detected in all groups that had received 1alpha,25(OH)2D3 compared with the vehicle only and nontreated groups (10(-7) M: 7.4 +/- 1.2 cells/mm2, 10(-8) M: 7.2 +/- 2.0 cells/mm2, 10(-9) M: 6.2 +/- 0.7 cells/mm2). Moderate inhibition of corneal vascularization was observed in the 10(-7) M 1alpha,25(OH)2D3 group, but not the other groups. CONCLUSIONS: Topical administration of 1alpha,25(OH)2D3 can be effective in suppressing ocular surface inflammation by inhibiting LC migration into mouse corneas.

Administration, Topical↗

[Hospitalization reduction by an asthma tele-medicine system].

We examined an effectiveness of a new asthma telemedicine system in reducing hospitalizations using a multi-site randomized control study. In this program, a nurse under physician supervision monitors the patient's airway status at home and provides instructions to individuals via the telephone, helping them manage exacerbations as well as reinforcing proper use of a zone-controlled management plan. Patients with a high risk for hospitalization were screened based on the numbers of emergency room visits and hospitalizations found in a previous study and randomly assigned to either the telemedicine or control group. After a six-month study period, an 83% reduction in hospitalization was demonstrated in the telemedicine group versus the control group, with a P value of 0.01. Improvement of peak expiratory flow and symptoms were also shown in the study group. We conclude that the key success factors in home asthma management for poorly controlled asthma patients are early detection of exacerbations through daily peak flow monitoring, compliance with prescribed daily prophylactic anti-inflammatory steroid medications, and immediate action as specified by a zone-controlled action plan upon the first signs of deterioration.

Aged↗

[Successful treatment of steroid-resistant bronchiolitis obliterans-organizing pneumonia with orally administered cyclosporin and pirfenidone].

A 27-year-old man with fever and dyspnea was admitted to our hospital. Chest computed tomography and a lung biopsy were performed, and bronchiolitis obliterans-organizing pneumonia (BOOP) was diagnosed. The patient was treated with corticosteroid, and a marked improvement was noted. However, when the dosage was tapered, BOOP recurred. Although the dosage was increased again, the corticosteroid alone was no longer effective against BOOP. While continuing with corticosteroid therapy, we also put the patient on a daily regimen of cyclosporin and pirfenidone, a recently developed anti-fibrotic agent. Both drugs were administered orally, and were so effective that we gradually decreased the dosage of corticosteroid. Several journals have reported that cyclosporin may be effective in the treatment of interstitial pneumonitis associated with collagen disease. We concluded that cyclosporin may also be useful in the treatment of refractory BOOP.

Administration, Oral↗

Langerhans cells, orthotopic corneal allografts, and direct and indirect pathways of T-cell allorecognition.

PURPOSE: To determine after orthotopic corneal allografting the role of Langerhans cells in activation of T cells via the direct and indirect pathways of allorecognition and the relationship between these pathways and the rapidity of graft rejection. METHODS: Corneas from eyes of normal mice and from eyes after superficial cauterization were grafted to eyes of major histocompatibility complex (MHC) and/or minor histocompatibility (H)-disparate recipient mice. The grafts were analyzed through time for content of class 1 MHC- bearing Langerhans cells and for rejection or acceptance. Graft recipients were evaluated for acquisition of delayed hypersensitivity (DH) and cytotoxic T cells (Tc) directed at donor MHC and minor H alloantigens. RESULTS: Langerhans cells migrated more rapidly into epithelium of cauterized grafts than normal grafts. Unlike normal grafts, the vast majority of cauterized allografts were rejected within 2 weeks. Normal grafts induced neither DH nor Tc directed at donor MHC antigens, whereas cauterized grafts induced both DH and Tc specific for donor MHC. All grafts induced DH directed at donor minor H antigens, but only rejected grafts correlated with acquisition of Tc directed at donor minor H antigens. CONCLUSIONS. The rapidity of orthotopic corneal allograft rejection correlated with density of Langerhans cells within epithelium and with acquisition of donor-specific DH and Tc. Although recipient-derived Langerhans cells promoted minor H-specific, self-MHC-restricted T cells (indirect pathway) and subacute graft rejection, donor-derived Langerhans cells promoted early, acute rejection in conjunction with allogeneic MHC-specific Tc (direct pathway).

Acute Disease↗

[A case of idiopathic subglottic stenosis successfully treated with endoscopic laser treatment].

A 24-year-old woman presented with an abnormal sound in her neck. She had no history of previous surgery, endotracheal intubation or neck trauma. She had been aware of this abnormal sound since she was 12 years old, but paid no attention to it. She had been recommended to visit a hospital for a neck examination. Stridor was heared in the neck ["coming from the throat"?]. Peak flow was markedly suppressed in pulmonary function tests, and the flow volume loop indicated upper airway stenosis. Bronchoscopy revealed subglottic tracheal stenosis, and magnetic resonance imaging showed that the cricoid cartilage was normal. Nd-YAG laser treatment was performed in Mitsui Memorial Hospital and her symptoms were improved. Biopsy of the stenotic area of the trachea showed dense fibrous tissue proliferation in the submucosa. Neither granuloma nor vasculitis was found in the biopsy specimen. No systemic disease capable of inducing tracheal stenosis was found on systemic examination. From these clinical and pathological findings, we diagnosed idiopathic subglottic stenosis.

Adult↗