[Chronic obstructive pulmonary disease and physical activity].
Explore the source record for details and available documents.
Exercise↗
Biomedical subjects
K Nakata
Publications and source records attributed to K Nakata.
[A clinicopathological study of pulmonary cryptococcosis--chest CT and pathologic correlation].
We reviewed the clinicopathological features in 12 patients (7 males and 5 females; mean age 54 yr) with pulmonary cryptococcosis. Eleven of the patients were asymptomatic and the disease was detected by chest radiograph abnormalities. The underlying systemic disease had been diagnosed as diabetes mellitus in two. Chest CT scans showed a solitary nodule in 9 of the 12 patients, multiple nodules in 2, and infiltration in 1. The nodular diameter was less than 2 cm in 10 of the 12. All nodules were located in the subpleural region. On the chest CT, cavitary nodules, scattered nodules, or both, and spiculated nodules were difficult to distinguish from pulmonary tuberculosis and primary lung cancer, respectively. According to McDonnell's pathological classification of pulmonary cryptococcosis, the resected 8 lungs revealed peripheral pulmonary granuloma in 5 and granulomatous pneumonia in 3. It is important to perform a pathological examination for the diagnosis of pulmonary cryptococcosis to avoid misdiagnosis as lung cancer or pulmonary tuberculosis.
Adult↗
Development of a new silicone membrane oxygenator for ECMO.
Two types small and efficient ECMO oxygenators were developed utilizing the most up to date hollow fiber technology. Newly silicone hollow fibers possess sufficient mechanical strength while maintaining ultra thin walls of 50 micro meter. Two types of oxygenators were made with this fiber. The fiber length for the type 1 module is 150mm with a priming volume 194 cc (surface area 1.3 m(2)) and type 2 has a fiber length of 100 mm with a 144 cc priming volume (the surface area 0.8 m(2)). The studies were performed at 0.5, 1.0 and 2.0 L/min of blood flow and these oxygenators demonstrated. O(2) gas transfer rate of 69+/-4 ml/min/L for type 1 and 68+/-6 ml/min/L for type 2. The CO(2) gas transfer rate was 25+/-2 ml/min/L for type 1 and 32+/-2 ml/min/L for type 2. These results demonstrate type 2 oxygenator has similar gas exchange capabilities to those of Kolobows' oxygenator which has about 2.0 times larger surface area. Additionally, comparative hemolysis tests were preformed with this new oxygenator and the Kolbow. The NIH value was 0.006 (g/100 L) for the type 1 oxygenator and 0.01 (g/100 L) for the Kolbow oxygenator. These results suggested that this ECMO oxygenator had sufficient gas exchange performance in spite of being smaller and induced minimal blood damage.
Equipment Design↗
[The status of NIHS Information and Computing Infrastructure (NICI)].
From 1999 to 2000, NIHS Information and Computing Infrastructure (NICI) were newly renovated. The purposes of the renovation are (1) the improvement of the communication for business works in NIHS, (2) supporting for the research, (3) supporting for the administration work. The Internet connection speed was upgraded from 256 Kbps to 1.5 Mbps. The high quality network sever machines and database server machines were installed. The large-scale software systems were renewed their versions. Four experimental stations for medical plants at Hokkaido, Izu, Wakayama and Tanegashima connected to NIHS at Tokyo or Osaka branch by ISDN. We describe the providing information on NIHS home page, and how to utilize NICI for our research and official works.
Databases, Factual↗
[Development of research support environment for molecular pharmacology and toxicology].
The Chem-Bio Informatics division has developed the institute-wide computer network which is connected to the Internet via IMnet (Inter Ministry Network) sponsored by the Government. We call the network and associated information and computing infrastructure as NICI, the NIHS Information and Computing Infrastructure. The primary goal of NICI is to provide general communication environment such as e-mails, and the second goal is to provide WWW environment. Accomplishing these two goals the division is now challenging to develop information and computing environment that directly supports pharmaceutical and toxicological research. The prototype of this environment which consists of various chemical and biomolecular databases and computing tools has been developed under the name of MOBI-DICS. The concept and vision on how to extend the prototype to institute-wide infrastructure was discussed.
Computational Biology↗
Long-term efficacy of immunization against hepatitis B virus in infants at high-risk analyzed by polymerase chain reaction.
Perinatal transmission of hepatitis B virus (HBV) is a common cause of chronic infection. In the present study, we evaluated the long-term efficacy of immunization against HBV in infants at high-risk, by using polymerase chain reaction (PCR). Two hundred and fifty-one infants received hepatitis B immunoglobulin at birth and a course of hepatitis B vaccine within 6 months of age between 1981 and 1993. Of 251 infants, 203 (81%) and 97 (39%) were followed until 1 and 4-6 years of age, respectively. HBV-DNA was detected by PCR in 74 (36%) of 203 children at 1 year of age, while the prevalence rate of children positive for HBV-DNA decreased to 14 (14%) of 97 children at 4-6 years of age, including 2 children who had the breakthrough variants of HBV. Our results indicate that most of HBV infections occur early, during the first year, and that immunization against HBV effectively protects infants at high-risk against viral transmission, at least up to 4-6 years of age.
Adult↗
p48 (ISGF-3gamma) is involved in interferon-alpha-induced suppression of hepatitis B virus enhancer-1 activity.
Interferon-alpha (IFN-alpha) suppresses hepatitis B virus (HBV) gene expression by reducing its enhancer-1 activity. IFN-alpha induces transcription factors, interferon-stimulated gene factor 3 (ISGF3), and interferon regulatory factor-1 (IRF-1), which activate interferon-inducible gene expression through binding to the interferon-stimulated regulatory element (ISRE) "AGTTTCNNTTTCNC" in the gene promoters. We found the ISRE-like sequence "AGGCTTTCACTTTCTC" in the HBV enhancer-1 region and elucidated the role of this sequence. Gel mobility shift assay showed binding of in vitro translated IRF-1 and in vitro translated p48 (ISGF3-gamma), which is a component of ISGF3 to this sequence. However, nuclear extracts binding to this sequence from human hepatoma cells (HuH-7) treated with IFN-alpha contained only the protein consisted of p48. In transfection experiments, IFN-alpha suppressed the HBV enhancer-1 activity, and overexpression of p48 enhanced this inhibitory effect. Both mutation and deletion of the ISRE-like sequence in the HBV enhancer-1 region reduced the suppressive effect of IFN-alpha. Our results suggest that the ISRE-like sequence in the HBV enhancer-1 can interact with the protein containing p48 and mediate the IFN-alpha-induced suppression of the enhancer activity.
Base Sequence↗
Idiopathic pulmonary alveolar proteinosis as an autoimmune disease with neutralizing antibody against granulocyte/macrophage colony-stimulating factor.
Idiopathic pulmonary alveolar proteinosis (I-PAP) is a rare disease of unknown etiology in which the alveoli fill with lipoproteinaceous material. We report here that I-PAP is an autoimmune disease with neutralizing antibody of immunoglobulin G isotype against granulocyte/macrophage colony-stimulating factor (GM-CSF). The antibody was found to be present in all specimens of bronchoalveolar lavage fluid obtained from 11 I-PAP patients but not in samples from 2 secondary PAP patients, 53 normal subjects, and 14 patients with other lung diseases. It specifically bound GM-CSF and neutralized bioactivity of the cytokine in vitro. The antibody was also found in sera from all I-PAP patients examined but not in sera from a secondary PAP patient or normal subjects, indicating that it exists systemically in I-PAP patients. As lack of GM-CSF signaling causes PAP in congenital cases and PAP-like disease in murine models, our findings strongly suggest that neutralization of GM-CSF bioactivity by the antibody causes dysfunction of alveolar macrophages, which results in reduced surfactant clearance.
Autoantibodies↗
Characterization of a novel member of the FGF family, XFGF-20, in Xenopus laevis.
The cDNA for a novel member of the FGF family (XFGF-20) was isolated from a Xenopus cDNA library prepared at the tailbud stage using as a probe the product of degenerate PCR performed with primers based on mammalian FGF-9s. This cDNA was 1860 bp long, and contained a single open reading frame that encoded 208 amino acid residues. The deduced amino acid sequence contained a motif characteristic of the FGF family and it was similar (73.1% overall homology) to XFGF-9 but differed from XFGF-9 in its amino-terminal region (33.3% homology). XFGF-20 mRNA was expressed only zygotically in embryos at and after the blastula stage, but it was also specifically expressed in the stomach and testis of adults. By contrast, XFGF-9 mRNA was expressed maternally in eggs and in many adult tissues. When XFGF-20 mRNA was overexpressed in early embryos, gastrulation was abnormal and development of anterior structures was suppressed. In such embryos, the expression of the Xbra transcript was suppressed during gastrulation while the expression of the transcripts of cerberus, Siamois, dkk-1, chordin, and Xotx-2 genes was normal. These results suggest that correct expression of XFGF-20 during gastrulation is required for the formation of normal head structures in Xenopus laevis during embryogenesis and that expression of the Xbra gene mediates this phenomenon.
Amino Acid Sequence↗
The interaction between human and bovine serum albumin and zinc studied by a competitive spectrophotometry.
The binding of zinc to human serum albumin (HSA) and bovine serum albumin (BSA) has been studied by a competitive spectrophotometry. The indictor ligand, 5-Br-PAPS, as well as its metal complexes, ML and ML2, having intense colors with sufficient separate absorption peaks permits the analysis of the interaction between zinc and HSA or BSA. The results show that zinc binds to both albumins in the molar ratio of 1:1 at pH 6-8. The apparent association constants of Zn-HSA and Zn-BSA decrease with decreasing pH. The pH dependence of the constants for both Zn-HSA and Zn-BSA indicates the 1:1 competition between metal ions and hydrogen ions for the binding site. The intrinsic association constants of the metal and the proton are found to be log KZn-HSA = 7.1 +/- 0.2 and log KH-HSA = 8.2 +/- 0.3 for HSA and log KZn-BSA = 7.6 +/- 0.2 and log KH-BSA = 8.2 +/- 0.3 for BSA, respectively.
Animals↗
Variation in the number of CAG repeats in the Machado-Joseph disease gene (MJD1) in the Japanese population.
Variation in the number of CAG repeats in the Machado-Joseph disease gene (MJD1) was examined by polymerase chain reaction and denaturing polyacrylamide gel electrophoresis analysis of 2134 normal and 135 affected chromosomes of Japanese individuals. The number of repeats ranged from 14 to 47 in normal alleles and from 61 to 84 in disease-associated alleles. The most frequent and lowest number of repeats was 14. The size distribution of normal MJD1 alleles did not fit a normal distribution curve, but was tetramodal. Repeats from 14 to 17, 18 to 23, 24 to 25, and 26 to 47 units were designated groups A through D, respectively. When examined Hardy-Weinberg equilibrium by chi-square analysis of goodness of fit: no evidence of significant deviation from the Hardy-Weinberg equilibrium was observed [x2=4.248<16.919 (P=0.05), df=9]. The observed distribution peak of normal MJD1 alleles corresponding to peptides containing 10, 15, 20, and 24 glutamine suggests that stretches of 5 and 10 glutamine might constitute a functional domain of human MJD1.
Adolescent↗
Lungs of patients with idiopathic pulmonary alveolar proteinosis express a factor which neutralizes granulocyte-macrophage colony stimulating factor.
Mice deficient in granulocyte-macrophage colony stimulating factor (GM-CSF) develop pulmonary alveolar proteinosis (PAP). We found that bronchoalveolar lavage fluid (BALF) from 11 patients with idiopathic pulmonary alveolar proteinosis (IPAP) suppressed the growth of peripheral blood monocytes and TF-1 cells, a cell line dependent on either GM-CSF or interleukin-3 (IL-3). The inhibitory effect of PAP-BALF occurred only when TF-1 cells were cultured with GM-CSF but not when cultured with IL-3, suggesting that PAP-BALF contains a factor that specifically interferes with GM-CSF function. 125I-GM-CSF binding to TF-1 cells was prevented in the presence of BALF from IPAP patients. Furthermore, cross-linking of 125I-GM-CSF to IPAP-BALF produced two major bands on SDS-PAGE; these bands were not observed in normal BALF. These data suggest that IPAP is caused by expression of binding factor(s) which inhibit GM-CSF function in the lung.
Binding, Competitive↗
Augmented proliferation of human alveolar macrophages after allogeneic bone marrow transplantation.
After allogeneic bone marrow transplantation (allo-BMT), recipient alveolar macrophages (AM) are gradually replaced by AM of the donor origin. An influx of mononuclear phagocytes of donor origin to the lung is responsible for the repopulation, but the detailed kinetics remain unclear. We therefore studied 24 BMT recipients who underwent bronchoalveolar lavage (BAL) from 24 to 83 days after BMT. AM cell number, size, morphology, proliferating ability, and genotype of AM were measured. Before day 50, the number and size of AM in BAL fluid were similar to those of normal nonsmokers. However, after day 50, the mean number of AM increased threefold and the mean cell size decreased due to the increase of small AM. These small cells are presumably of donor origin based on DNA fingerprinting analysis and based on fluorescence in situ hybridization for the Y chromosome in a sex-mismatched case. Immunohistochemistry and cell cycle analysis demonstrated that the increase in AM number coincided with a remarkable increase of AM expressing proliferating cell nuclear antigen, suggesting that small AM are proliferating. This is the first report representing that augmented proliferation of donor AM in situ may contribute to the reconstitution of AM population after BMT.
Adolescent↗
Activation of caspase-8 in transforming growth factor-beta-induced apoptosis of human hepatoma cells.
Transforming growth factor-beta1 (TGF-beta1) has been shown to induce apoptosis in normal or transformed hepatocytes. To elucidate the biochemical pathways leading to apoptosis induced by TGF-beta1 in human hepatoma cells (HuH-7), we examined the expression of Bcl-2-related proteins and X-chromosome-linked inhibitor of apoptosis (XIAP), and activation of the caspase cascade following TGF-beta1 treatment. Bcl-xL expression began to decline at 12 hours after TGF-beta1 treatment and progressively decreased to very low levels in a time-dependent manner. Bax expression showed a little change throughout the experiment. On the other hand, activation of caspase-8 was clearly observed at 36 hours after TGF-beta1 treatment, followed by activation of caspase-9, and caspase-3 was activated at 48 hours after treatment at which time apoptosis of HuH-7 cells was observed. TGF-beta1 significantly decreased XIAP expression in HuH-7 cells. Addition of an inhibitor of caspase-8 or caspase-3 (IETD-FMK or DEVD-CHO) markedly inhibited TGF-beta1-induced apoptosis of HuH-7 cells. Fas/Fas ligand (FasL) interactions in HuH-7 cells were not involved in the apoptotic process. Furthermore, epidermal growth factor (EGF) also completely inhibited TGF-beta1-induced apoptosis of HuH-7 cells by inhibiting activation of the caspase cascade. Our results suggested that activation of caspase-3 initiated through caspase-8 activation is involved in the apoptotic process induced by TGF-beta1 in HuH-7 cells. Our results also showed that down-regulation of the expression of Bcl-xL and XIAP by TGF-beta1 may facilitate activation of caspase-3 in these cells.
Apoptosis↗
Feeding experience affects web relocation and investment in web threads in an orb-web spider, Cyclosa argenteoalba.
Orb-web spiders often relocate their webs when they assess a web site as prey poor. When a spider spins its web at a new site, it may not be able to assess the prey availability at the site accurately on the first day, owing to stochastic variation in foraging success, but it is gradually able to make an assessment. Therefore, a spider's foraging behaviour may change according to how long it has been at its current web site. To test this possibility, we conducted a prey removal experiment, with the spider Cyclosa argenteoalba, to compare the response to prey deprivation of spiders that were on new sites with that of spiders that had been at a site for several days. Spiders in both groups had a higher relocation rate than the natural rate, but more spiders in the new-site group relocated their webs. Spiders thus seemed to use previous experience of prey capture at a web site to decide whether to relocate their web. The total length of silk thread in a web was greater on the second day at a new web site than on the first. We suggest that spiders minimize their investment in web threads until they are certain that the web site is prey rich. Copyright 1999 The Association for the Study of Animal Behaviour.
Journal Article↗
Cyclosporin A increases tear fluid secretion via release of sensory neurotransmitters and muscarinic pathway in mice.
Cyclosporin A, an immunosuppressant, has the potential to increase tear fluid secretion through mechanisms which are not yet well understood. To gain insight into this question, we investigated the effect of cyclosporin A containing eyedrops on lacrimation in normal mice. Topical application of 0.1% cyclosporin A eyedrops for 3 days significantly increased lacrimation. This response was completely blocked by pre-exposure to 1% capsaicin. Immunohistochemical analysis revealed that capsaicin treatment depleted substance P from the lacrimal gland. Furthermore, following 1% atropine treatment, which completely blocks pilocarpine-stimulated (500 micrograms kg-1, i.p.) lacrimation, application of 0.1% cyclosporin A eyedrops significantly increased lacrimation. However, this increase was less than the response seen with 0.1% cyclosporin A in the absence of atropine. Interestingly, substance P-induced tear secretion was also partially inhibited in atropine treated mice. These results suggest that cyclosporin A accelerates tear secretion by releasing neurotransmitters from sensory nerve endings which interacts with the parasympathetic nerves.
Administration, Topical↗
Establishment of T-helper type 2 clone-induced eosinophilia in mouse conjunctiva.
Eosinophil infiltration is one of the aspects of the inflammatory response to an allergen. The aim of this study was to establish T-helper type-2 (Th2)-induced conjunctival eosinophilia in mice to evaluate the effect of anti-allergic drugs. Th2 clone, D10.G4.1. (D10) with its specific antigen, conalbumin was co-injected into conjunctival tissue in mice. At 3-6 hr after D10 injection, eosinophil and neutrophil recruitment into conjunctival tissue was observed. Cellular infiltration into conjunctival tissue reached a maximum level between 24-48 hr after D10 injection. The number of eosinophils which infiltrated after 24 hr was dose dependent on T cell injection titer from 1x10(4), 1x10(5)to 1x10(6)cells site-1. The ratio of eosinophils to neutrophils at 24 hr after D10 cell (1x10(5)cells site-1) injection was about 9 to 1. The eosinophil infiltration into conjunctival tissue was significantly reduced by the intraperitoneal administration of anti-IL-5 monoclonal antibody (100 micrograms animal-1). Anti-IL-4 monoclonal antibody (500 micrograms animal-1) partially inhibited eosinophilia. The combined inhibitory effect of anti-IL-4 and anti-IL-5 monoclonal antibodies was larger than the inhibitory effect of anti-IL-5 monoclonal antibody alone. In conclusion, a Th2-induced mouse conjunctival eosinophilia model was established in which D10 activation results in IL-4 and IL-5 release. These cytokines elicit eosiniophil infiltration. This response shows that the model will be effective for screening candidates of anti-allergic drugs.
Animals↗
An experimental allergic conjunctivitis induced by topical and repetitive applications of Japanese cedar pollens in guinea pigs.
OBJECTIVE AND DESIGN: To develop a model of experimental allergic conjunctivitis, guinea pigs were given repetitive and topical applications of Japanese cedar pollen as an antigen, and the resulting allergic reaction was characterised. SUBJECTS: Male Hartley guinea pigs. TREATMENT: Guinea pigs were sensitised by insertion of small gelatin sponge pieces (3 pieces/eye, both eyes) containing the pollen extracts + Al(OH)3 into the palpebra superior/inferior sulci of both eyes for 8 h/day for 6 days. Then the animals were challenged by dropping pollen suspension in each eye once every week. METHODS: Time-course changes of conjunctivitis intensity score (CIS), which represents oedema and redness, and scratching frequency, and gamma1 and IgE levels in sera were assessed following the respective 1st-17th challenges. Ophthalmic lavage was performed to assay for albumin leakage and migrated leukocytes at each of the odd-numbered challenges. RESULTS: At relatively early stages of the repeated challenge, only a gradual increase of CIS was observed. However, thereafter, considerably higher CIS with the maximum at 30 min after the challenge was provoked at the 12th-17th challenges. Quite interestingly, there were differences in the CIS between the right and left eyes, depending on the individuals. Scratching, and albumin leakage and neutrophil influx into the lavage fluid were also developed during the challenges. Although the anaphylactic antibodies against the antigen were detected in the sera from half of the animals, the levels were not correlated to severity of the symptoms. CONCLUSIONS: The present sensitisation/challenge procedures are unique in terms of topical application of antigen. The lack of any correlation between the levels of the anaphylactic antibodies and severity of anaphylactic symptoms, and the difference of CIS between the left and right eyes of an individual strongly suggest that the anaphylactic antibodies are formed in locally limited tissue surrounding an eye. The present method should be useful for analysing the mechanisms of allergic conjunctivitis.
Administration, Topical↗