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Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 235 records · Page 13Linked to original sources

Intercellular cell adhesion molecule-1 regulates lymphocyte movement into intestinal microlymphatics of rat Peyer's patches.

The objective of this study was to determine whether specific adhesion molecules modulate lymphocyte movement from Peyer's patches into intestinal microlymphatics. The fluorochrome acridine orange was injected via a micropipette into Peyer's patches to fill lymphatics. The flux of labeled lymphocytes into intestinal microlymphatics was monitored with intravital fluorescence microscopy. The lymphatic microvessels in the perifollicular area of Peyer's patches were filled with lymphocytes, most of which remained within the lymphatics. Some lymphocytes became detached and were drained into intestinal lymph. Administration of antibodies directed against ICAM-1 significantly increased lymphocyte flux into interfollicular lymphatics. The immunohistochemical study showed intense ICAM-1 expression on the lymphocytes densely packed in the lymphatics surrounding follicles in Peyer's patches. A large number of lymphocytes are normally sequestered in the lymphatic network of Peyer's patches. This sequestration of lymphocytes is largely mediated by ICAM-1-dependent cell-cell interactions.

Animals↗

[Respiratory function tests--current and future perspective].

The apparatus for the respiratory function test have recently made a great progress and become very easy to handle owing to the development of computer technology and medical ordering system. However, the respiratory function tests depend its result on the cooperation of patients. Thus, it is important for the medical technician to obtain the maximum efforts and cooperation of the patients in the testing. In the sense, the standardization of the testing should be done urgently regarding procedures, softwares, hardwares and maintenance of apparatus. In the future perspectives, we would like to emphasize following 3 points. First, more noninvasive and sophisticated testing methods and instruments should be developed, since the patients' age will become more and more old and vigorous active cooperation may not be possible for the assessment of respiratory function. The testing for the transplantation of lung should also be developed. Second, the development of screening test and its performance for the routine medical check for the local inhabitants have been important for the early detection, treatment, and follow up of respiratory diseases. Finally, the medical technician should be prepared so that the testing is available when it is needed.

Forced Expiratory Flow Rates↗

Inactivation of Cryptosporidium parvum oocysts in field soil.

Cryptosporidium parvum oocysts from dairy calves are believed to regularly contaminate watersheds. Identifying oocysts and measuring their viability in the natural environment are important elements in estimating the risk posed by this resistant organism. A 152 day field study was conducted to measure the viabilities of oocysts inoculated into 25 sampling points. Water potential, pH, and ammonium content were also measured at the same 25 sampling sites. A three-dimensional mapping program (Surfer) was used to create 3-D maps of the viabilities of C. parvum oocysts and other factors measured during the experiment. The results indicate that 3-D graphical presentation may be a useful means to identify potential sites of greatest risk of oocyst survival and could indicate areas where natural conditions are causing the most rapid oocyst inactivation, and this method can be a means for the future measurement of microorganism inactivation in the natural environment.

Animals↗

[Transcriptional control of vitamin D1alpha-hydroxylase gene by PTH].

The vitamin D1alpha-hydroxylase plays a critical role in the vitamin D actions as a key enzyme for vitamin D biosynthesis. Reflecting its significant role, the gene expression is under control of multiple hormones. PTH and calcitonin up-regulate, but vitamin D represses the expression of this gene. The functional analyses of the gene promoter identified the regulatory element and the binding factor to control transcription in response to hormones.

English Abstract↗

[Molucular mechanism of vitamin D actions].

Vitamin D has roles in a variety of biological actions such as calcium homeostasis, cell proliferation and cell differentiation in many target tissues. Most of such biological actions of vitamin D are now considered to be exerted through nuclear vitamin D receptor (VDR) -mediated control of target genes. VDR belongs to the nuclear hormone receptor superfamily and acts as a ligand-inducible transcription factor. For the ligand-induced transctivation of VDR, the coactivator complexes have been recently shown essential. The function of VDR as a ligand-induced transcription factor is overviewed.

English Abstract↗

FGF10 acts as a major ligand for FGF receptor 2 IIIb in mouse multi-organ development.

FGF receptor 2 isoform IIIb (FGFR2b), originally discovered as a receptor for FGF7, is known to be an important receptor in vertebrate morphogenesis, because FGFR2b null mice exhibit agenesis or dysgenesis of various organs, which undergo budding and branching morphogenesis. Since FGF7 null mice do not exhibit marked defects in organogenesis, it has been considered that other FGF(s) than FGF7 might function as a major ligand for FGFR2b during organogenesis. One of the candidate ligands is FGF10, because FGF10 binds to FGFR2b with high affinity and the formation of the limb and lung is arrested in FGF10 null mice as found in FGFR2b-deficient mice. Previous analyses of FGF10 null mice revealed that FGF10 is required for limb and lung development. To elucidate the role of FGF10 in wide-range organogenesis, we further analyzed the phenotypes of the FGF10 knockout mice. We found diverse phenotypes closely related to those for FGFR2b-deficient mice, which includes the absence of thyroid, pituitary, and salivary glands, while minor defects were observed in the formation of teeth, kidneys, hair follicles, and digestive organs. These results suggest that FGF10 acts as a major ligand for FGFR2b in mouse multi-organ development.

Animals↗

Strain-dependent antibody response induced by DNA immunization.

The antibody (Ab) response induced by DNA-based immunization was compared in various strains of inbred, H-2 congenic and outbred mice with different haplotypes of mouse major histocompatibility complex (H-2). Two different plasmid expression vectors encoding Aequorea victoria green fluorescent protein (GFP) or Escherichia coli, beta-galactosidase (beta-gal) were introduced into quadriceps muscle, and Ab production was examined using both enzyme-linked immunosorbent assay and immunoblot analysis. The beta-gal plasmid DNA immunization induced strong Ab production in all inbred, H-2 congenic and outbred strains at the early stages of immunization. By comparison with beta-gal peptide immunization, the degree of Ab response was H-2 haplotype-dependent. On the other hand, Ab production by GFP plasmid DNA immunization was observed in outbred strains, but not in some of the inbred and H-2 congenic strains. Also, outbred strains showed a high Ab response compared with other inbred and H-2 congenic strains by GFP peptide immunization. Reverse transcription-polymerase chain reaction analysis demonstrated the presence of GFP or beta-gal transcripts at the DNA inoculation site in all the strains studied, even in inbred and H-2 congenic strains which showed no Ab production by GFP plasmid DNA immunization. These results indicate that the difference in Ab response induced by DNA immunization as well as by peptide immunization depends upon the H-2 haplotypes of host strains.

Animals↗

Identification of cDNAs encoding two novel nuclear proteins, IMUP-1 and IMUP-2, upregulated in SV40-immortalized human fibroblasts.

Using a model system of young, senescent and SV40-immortalized WI-38 fibroblasts, we identified two mRNAs upregulated in immortalized cells (imup-1, immortalization-upregulated protein 1, and imup-2). Compared to normal tissues, both genes were more frequently expressed in cancer cells. The open reading frame of imup-1 spans 321bp, coding for a 10.9 kDa protein of 106 amino acids, while an insertion of 59bp in the otherwise identical mRNA of imup-2 leads to a frameshift, resulting in an 8.5 kDa protein of 85 amino acids. Database searches identified these genes on chromosome 19, which could account for the cloned imup-1 and imup-2 transcripts by alternative splicing. Southern blot analysis of digested genomic DNA confirmed that both transcripts are derived from a single locus. The expressed proteins IMUP-1 and IMUP-2 share 46 identical N-terminal amino acids, whereas the C-termini are unrelated. Green fluorescent protein-fusions of both IMUP-1 and IMUP-2 accumulated in the nucleus of HeLa cells. The C-terminus of IMUP-1 contains a bipartite nuclear localization signal, the deletion of which impaired nuclear translocation. In-vitro translated proteins bound to poly(rG), but did not interact with single-stranded DNA or double-stranded DNA. The nuclear localization of IMUP-1 and IMUP-2 as well as the upregulation of both underlying mRNAs in immortalized cells suggest a function in immortalization.

Alternative Splicing↗

Ligand type-specific interactions of peroxisome proliferator-activated receptor gamma with transcriptional coactivators.

The nuclear peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily and acts as a ligand-dependent transcription factor mediating adipocyte differentiation, cell proliferation and inflammatory processes, and modulation of insulin sensitivity. Members of the 160-kDa protein (SRC-1/TIF2/AIB-1) family of coactivators, CBP/p300 and TRAP220/DRIP205, are shown to interact directly with PPARgamma and potentiate nuclear receptor transactivation function in a ligand-dependent fashion. Because PPARgamma ligands exert partially overlapping but distinct subsets of biological action through PPARgamma binding, we wished to examine whether interactions between PPARgamma and known coactivators were induced to the same extent by different classes of PPARgamma ligand. The natural ligand 15-deoxy-Delta12,14-prostaglandin J(2) induced PPARgamma interactions with all coactivators tested (SRC-1, TIF2, AIB-1, p300, TRAP220/DRIP205) in yeast and mammalian two-hybrid assays, as well as in a glutathione S-transferase pull-down assay. However, under the same conditions troglitazone, a synthetic PPARgamma ligand that acts as an antidiabetic agent, did not induce PPARgamma interactions with any of the coactivators. Our findings suggest that ligand binding may alter PPARgamma structure in a ligand type-specific way, resulting in distinct PPARgamma-coactivator interactions.

Animals↗

Skin abnormalities generated by temporally controlled RXRalpha mutations in mouse epidermis.

Nuclear receptors for retinoids (RARs) and vitamin D (VDR), and for some other ligands (TRs, PPARs and LXRs), maybe critical in the development and homeostasis of mammalian epidermis. It is believed that these receptors form heterodimers with retinoid X receptors (RXRs) to act as transcriptional regulators. However, most genetic approaches aimed at establishing their physiological functions in the skin have been inconclusive owing either to pleiotropic effects and redundancies between receptor isotypes in gene knockouts, or to equivocal interpretation of dominant-negative mutant studies in transgenic mice. Moreover, knockout of RXRalpha, the main skin RXR isotype, is lethal in utero before skin formation. Here we have resolved these problems by developing an efficient technique to create spatiotemporally controlled somatic mutations in the mouse. We used tamoxifen-inducible Cre-ER(T) recombinases to ablate RXRalpha selectively in adult mouse keratinocytes. We show that RXRalpha has key roles in hair cycling, probably through RXR/VDR heterodimers, and in epidermal keratinocyte proliferation and differentiation.

Alleles↗

Study of Salt Effects on the Micelle-Monomer Exchange Process of Octyl-, Decyl-, and Dodecyltrimethylammonium Bromide in Aqueous Solutions by Means of Ultrasonic Relaxation Spectroscopy.

The effects of added salt on the micelle-monomer exchange process of octyl- and decyltrimethylammonium bromide were investigated by means of ultrasonic relaxation techniques. Using the Aniansson-Wall model, the micellar distribution width sigma and the dissociation rate constant k(-1) of the micelle-monomer exchange process were determined as functions of carbon number and of added salt concentration in aqueous solutions of a series of tetraalkylammonium bromide-NaBr systems and discussed on the basis of the Aniansson-Wall-Teubner model. From the rate constant of the micelle-monomer exchange process, the total energy change for the transfer of the alkyl chain of the surfactant ion from the interior of the micelle to a position where its terminal methyl groups is at the surface of the micelles was estimated and compared with those calculated by the Gouy-Chapmann model of the electric double-layer theory. Copyright 2000 Academic Press.

Journal Article↗

Defective terminal differentiation and hypoplasia of the epidermis in mice lacking the Fgf10 gene.

Here, we characterized the skin and hair phenotype of mice lacking the fibroblast growth factor 10 gene (Fgf10), a newly identified member of the fibroblast growth factor family. Histological examination of Fgf10(-/-) newborn mouse skin revealed abnormalities in epidermal morphogenesis. The number of proliferating cells in the basal layer was decreased, the granular layer was hypoplastic and lacked distinctive keratohyaline granules and tonofibrils. The expression of loricrin, a marker of epidermal differentiation, was dramatically reduced. Despite the presence of Fgf10 transcripts in normal hair follicles, abnormalities of hair development were not observed in Fgf10(-/-) skin. These data suggest that Fgf10 is required for embryonic epidermal morphogenesis but is not essential for hair follicle development.

Animals↗

Cyclin E as a coactivator of the androgen receptor.

Androgens play an important role in the growth of prostate cancer, but the molecular mechanism that underlies development of resistance to antiandrogen therapy remains unknown. Cyclin E has now been shown to increase the transactivation activity of the human androgen receptor (AR) in the presence of its ligand dihydrotestosterone. The enhancement of AR activity by cyclin E was resistant to inhibition by the antiandrogen 5-hydroxyflutamide. Cyclin E was shown to bind directly to the COOH terminus portion of the AB domain of the AR, and to enhance its AF-1 transactivation function. These results suggest that cyclin E functions as a coactivator of the AR, and that aberrant expression of cyclin E in tumors may contribute to persistent activation of AR function, even during androgen ablation therapy.

Cell Line↗

Aberrant splicing of human Cu/Zn superoxide dismutase (SOD1) RNA transcripts.

Two abnormal SOD1 mRNAs, exon 2-skipping and exon 2 and 3-skipping species, were identified from occipital brain tissue of sporadic amyotrophic lateral sclerosis (ALS) patients carrying no mutations in the SOD1 gene. Both transcripts were ubiquitously expressed in non-neuronal as well as neuronal tissues from a subject without neurological diseases. The expression pattern did not show disease specificity or lesional selectivity associated with ALS. Transient expression studies revealed weak expression of the proteins derived from the exon 2-skipping SOD1 cDNA in a cell-free translation system but not in cells. The putative abnormal SOD1 protein may accumulate and exert toxic effects on motor neurons in ALS when the proteolytic system is disturbed by aging or some causal factors.

Adolescent↗