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Biomedical subjects

S Inui

Publications and source records attributed to S Inui.

At least 37 records · Page 2Linked to original sources
PubMed1998

Ig receptor binding protein 1 (alpha4) is associated with a rapamycin-sensitive signal transduction in lymphocytes through direct binding to the catalytic subunit of protein phosphatase 2A.

Rapamycin is an immunosuppressant that effectively controls various immune responses; however, its action in the signal transduction of lymphocytes has remained largely unknown. We show here that a phosphoprotein encoded by mouse alpha4 (malpha4) gene transmitting a signal through B-cell antigen receptor (BCR) is associated with the catalytic subunit of protein phosphatase 2A (PP2Ac). The middle region of alph4, consisting of 109 amino acids (94-202), associates directly with PP2Ac, irrespective of any other accessory molecule. Rapamycin treatment disrupts the association of PP2Ac/alpha4 in parallel with the inhibitory effect of lymphoid cell proliferation. The effect of rapamycin was inhibited with an excess amount of FK506 that potentially completes the binding to FKBP. Rapamycin treatment also suppresses the phosphatase activity of cells measured by in vitro phosphatase assay. Introduction of the malpha4 cDNA into Jurkat cells or the increased association of PP2Ac/alpha4 by the culture with low serum concentration confers cells with rapamycin resistance. Moreover, glutathione S-transferase (GST)-alpha4 augments the PP2A activity upon myelin basic protein (MBP) and histone in the in vitro assay. These results suggest that alpha4 acts as a positive regulator of PP2A and as a new target of rapamycin in the activation of lymphocytes.

Adaptor Proteins, Signal Transducing↗
PubMed1998

The gene structure and promoter analysis of mouse lymphocyte signal transduction molecule alpha 4 that is related to the yeast TAP42 involved in a rapamycin-sensitive pathway.

The mouse alpha 4 phosphoprotein encoding a component associated with the B cell antigen receptor (BCR)-mediated signal transduction is suggested to be involved in a unique rapamycin-sensitive pathway. We studied the structure and the molecular mechanism of the expression of alpha 4 gene by isolating two phage clones, named #10 and #23, covering entire exons of the mouse alpha 4 gene. The alpha 4 gene is located within about 25 kb and composed of six exons. To analyze the regulation of alpha 4 gene expression, we determined the nucleotide sequence toward 2 kb upstream of the translation start site of the alpha 4 gene. The 5'-flanking region does not contain a typical TATA box or the initiation consensus sequence, but it contains a CCAAT box, E-boxes, and several DNA binding motifs such as c-Myc, c-Myb, and c-Ets. Transcription of the alpha 4 gene starts at four different sites, determined by primer extension analysis, that were surrounded by Y-rich sequences. We further characterized the functional promoter of the alpha 4 gene at the region between -263 and the transcription start site of alpha 4 gene by luciferase assay system and suggested that the 5' upstream region of alpha 4 gene contains the silencer element of MT repetitive sequence.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Variation in the ratio of respirable particulates over inhalable particulates by type of dust workplace.

OBJECTIVE: The aim of the present study was to clarify the quantitative relationship between respirable particulates and inhalable particulates in various dust workplaces. METHODS: Both respirable particulate and inhalable particulate concentrations were measured in 1644 dust workplaces by means of elutriation, and the ratio of respirable particulate mass over that of inhalable particulate (R/I ratio) was calculated for each workplace. RESULTS: Statistical analyses showed that the R/I ratio varied substantially, depending on the type of dust work. The ratio was highest in welding workplaces (mean +/- SD: 53 +/- 19%) and lowest in foundries (23 +/- 16%); the former value suggests that respirable particulate exposure may be underestimated in substantial parts of welding work when only the occupational exposure limit for inhalable particulates is taken for compliance testing. CONCLUSIONS: Simple compliance with the limit for inhalable particulates is not sufficient, and the limit for respirable particulates should also be simultaneously cleared.

Dust↗
PubMed1998

Monitoring of occupational exposure to dichloromethane by diffuse vapor sampling and urinalysis.

OBJECTIVE: The aim of the present study was to develop valid methods for monitoring of occupational exposure to dichloromethane (DCM). METHODS: Carbon cloth as an adsorbent in diffusive sampling was tested for its capacity to adsorb DCM vapor and to retain adsorbed DCM after termination of the exposure. Urine samples collected from DCM-exposed workers were analyzed for DCM by the head-space technique. After extraction with carbon disulfide, DCM in the cloth was analyzed on a DB-WAX capillary column by flame-ionization detection gas chromatography (FID-GC) and DCM in urine was analyzed by electron-capture detection (ECD)-GC. RESULTS: The diffusive sampling with carbon cloth as an adsorbent is applicable to 4-h monitoring of exposure to up to 100 ppm DCM vapor. DCM concentrations detected in end-of-shift urine samples correlated linearly with time-weighted average DCM concentrations measured in the breathing-zone air of the exposed workers; essentially the same exposure-excretion relationship was obtained by vapor monitoring for the afternoon 4-h period as compared with a whole day (8-h) of vapor monitoring. There was no sex difference in the exposure-excretion relation. CONCLUSIONS: Both personal diffusive sampling (at up to 100 ppm DCM and for up to 4 h) and biological exposure monitoring by urinalysis for DCM are applicable in occupational health as reliable measures of exposure to this chlorinated hydrocarbon solvent.

Air Pollutants, Occupational↗
PubMed1998

Synchronization of normal human keratinocyte in culture: its application to the analysis of 1,25-dihydroxyvitamin D3 effects on cell cycle.

In this report, we applied the isoleucine-deprivation method to normal human keratinocytes in cultivation with serum-free MCDB153 medium. The growing cells were synchronized by transfer to MCDB153 medium prepared without isoleucine, and the degree of synchronization was analyzed by the cell cycle distribution and phosphorylation of retinoblastoma protein (pRB), one of the tumor suppressor gene products. 1,25-dihidroxyvitamin D3 (1,25(OH)2D3), a biologically active form of vitamin D3, is supposed to induce the differentiation and growth inhibition of human keratinocytes caused by cell cycle arrest. We examined its effect on cell cycle kinetics, especially progression from G1/G0 to S-phase, by using this synchronized system. We showed that 10(-6) M 1,25(OH)2D3 inhibited the progression from G1/G0 to S-phase strikingly in synchronized normal human keratinocytes.

Blotting, Northern↗
PubMed1998

Evaluation of RU58841 as an anti-androgen in prostate PC3 cells and a topical anti-alopecia agent in the bald scalp of stumptailed macaques.

The effect of androgen receptor transcriptional activation by RU58841, a nonsteroidal anti-androgen, was studied in the human prostate cancer PC3 cell line by cotransfection with wild-type androgen receptor (wt AR) and an androgen-responsive reporter (MMTV-ARE-CAT) construct. Anti-and rogens, hydroxyflutamide, and Casodex, and the antiestrogen, genistein, were studied in parallel for comparison with RU58841. The wt AR was activated only by the androgen dihydrotestosterone (DHT). Neither the anti-androgens nor antiestrogen can enhance AR transcriptional activity at 10(-11)-10(-7)M in PC3 cells. Hydroxyflutamide, RU58841, and Casodex, but not genistein, displayed competitively suppressive effects on DHT activation of wt AR. The potency of RU58841 was comparable to that of hydroxyflutamide. From this result, topical application of RU58841, which is considered to be a potential therapy for skin diseases, may induce systemic side effects. However, RU58841, on topical application, revealed a potent increase in density, thickening, and length of hair in the macaque model of androgenetic alopecia, whereas no systemic effects were detected. Together our results suggest that RU58841 may have potent antagonism to the wt AR and could be considered as a topically applied active anti-androgen for the treatment of androgen-dependent skin disorders, such as acne, androgenetic alopecia, and hirsutism.

Alopecia↗
PubMed1997

Expression and chromosomal localization of the human alpha 4/IGBP1 gene, the structure of which is closely related to the yeast TAP42 protein of the rapamycin-sensitive signal transduction pathway.

To study the function of the B cell signal transduction molecule alpha 4 (IGBP1), we isolated a human alpha 4 (IGBP1) gene that has sequence similarity to the yeast protein (TAP42) involved in the rapamycin-sensitive signal transduction pathway. The human alpha 4 has sequence identities with murine alpha 4 of 83.4% nucleotide and 82.9% amino acid sequence, and a stretch of consensus motifs in the carboxyl terminal is conserved among the related genes of human, mouse, yeast, and rice. The gene is expressed as a 1.4-kb mRNA in the spleen, lymph node, thymus, appendix, peripheral blood leukocytes, bone marrow, fetal liver, heart, brain, placenta, skeletal muscle, kidney, and pancreas. The anti-human alpha 4 antibody detected a 45-kDa protein in human lymphoid cell lines. Moreover, human alpha 4 (IGBP1) gene is located at q13.1-q13.3 on chromosome X.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Possible role of coexpression of CD9 with membrane-anchored heparin-binding EGF-like growth factor and amphiregulin in cultured human keratinocyte growth.

CD9 is a protein with 4 transmembrane domains, and functions as a cell surface antigen. We have previously reported that CD9 functions as an up-regulator of membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) activity, which is a potent mitogen as well as a soluble HB-EGF. Anti-CD9 antibodies can neutralize the juxtacrine activity of proHB-EGF when both CD9 and proHB-EGF are coexpressed. We demonstrated here: (1) the CD9 gene was transcribed and translated in the cultured human keratinocytes; (2) anti-CD9 antibody inhibited the approximately 50% growth of human keratinocytes in culture; (3) CD9 was coprecipitated with proHB-EGF and membrane-anchored amphiregulin (proAR), and (4) the transient coexpression of CD9 with proHB-EGF or proAR in mouse L cells up-regulated their juxtacrine growth factor activities. These results suggest that CD9 would make a heterodimer and/or trimer complex with proHB-EGF and proAR, and might cooperate with proHB-EGF and proAR for human keratinocyte growth in a juxtacrine manner.

Amphiregulin↗
PubMed1997

Monitoring of occupational exposure to 1-butanol by diffusive sampling and urinalysis.

OBJECTIVES: To investigate the possibility of applying diffusive air sampling and urinalysis (for mother compound and metabolites) to the monitoring of exposure of factory workers to 1-butanol. METHODS: The performance of carbon cloth in adsorbing 1-butanol vapor in air was studied by experimental exposure of the cloth to 1-butanol at 50, 100, 200 or 400 ppm for up to 10 h. 1-Butanol in the exposed cloth was extracted with carbon disulfide and this was followed by gas-chromatographic (GC) analysis. Urine samples were collected from factory workers occupationally exposed to 1-butanol and from rats exposed experimentally to 1-butanol vapour (up to 200 ppm). The urine samples were analyzed by GC without any pretreatment, or after treatment with hydrochloric acid or hydrolase preparation. RESULTS: The performance of the carbon cloth was such that it adsorbed 1-butanol in proportion to the concentration (up to 400 ppm) and the duration (up to 10 h) of exposure, and responded quantitatively to a 15-min exposure up to 400 ppm. The amount of 1-butanol (after enzymic or acid hydrolysis) in post-exposure urine samples from rats was proportional to the exposure intensity. The proportion of free 1-butanol in total 1-butanol (i.e., free+conjugated) in urine was higher after 100 or 200 ppm exposure (35-40%) than after 50 ppm exposure (about 8%). There was a significant increase in total 1-butanol concentration (but not in free 1-butanol) in shift-end urine samples of workers exposed to 1-butanol at concentrations up to 3 ppm. CONCLUSIONS: Diffusive sampling with carbon cloth as an adsorbent can be applied to ambient air monitoring of exposure to 1-butanol. Urinalysis for 1-butanol after hydrolysis is sensitive enough to detect occupational 1-butanol vapour exposure at 3 ppm.

1-Butanol↗
PubMed1997

Types of organic solvents used in small- to medium-scale industries in Japan; a nationwide field survey.

OBJECTIVE: The aim of the present survey is to identify organic solvents commonly used in various workplaces in Japan. METHODS: A total of 24 occupational health service institutions (OHSI) distributed nationwide in Japan offered data on types of solvent workplaces, types of solvents used therein, and the solvent concentrations surveyed in a 2-month period between April and May 1996 to form a data base (OHSI data base, consisting of 1597 cases). Separately, Kyoto Industrial Health Association (KIHA) offered information on 948 cases studied during a 1-year period ranging from April 1995 to March 1996 (KIHA data base). The two data bases were treated in parallel to examine the reproducibility of the results. RESULTS: Detection prevalence was very low (0-1%) for almost half of the 47 legally regulated solvents. Among the solvents in use, toluene was most frequently detected, although the prevalence appeared to be reduced as compared with that recorded for the early 1980s. The most frequently observed solvent combinations comprised toluene, xylenes, and ethyl acetate in the OHSI data base and toluene, xylenes, and methanol in the KIHA data base. Contrary to the case in the 1980s, dichloromethane was used more often than trichloroethylene as a degreasing agent in the present survey. No use was detected for carbon tetrachloride, chloroform, 1,2-dichloroethane, 1,2-dichloroethylene, or 1,1,2,2-tetrachloroethane except for research purposes. CONCLUSIONS: Toluene remained the most common solvent and was used in combination with xylenes, ethyl acetate, and methanol. There was an increase in the use of dichloromethane as a degreasing agent.

Acetates↗
PubMed1997

Mouse germinal center B cells with the xid mutation retain responsiveness to antimouse CD40 antibodies but diminish IL-5 responsiveness.

The germinal center (GC) develops in secondary lymphoid tissues in response to thymus-dependent (TD) antigens. To investigate the molecular mechanism of B cell differentiation in GC, we enriched GC B cells from spleen of TD antigen-immunized wild-type and X-linked immunodeficient (XID) mice, and examined the differentiation of GC B cells into antigen-specific IgG1 antibody-forming cells (AFC) in response to anti-CD40 mAb and cytokines. A significant proportion of freshly purified GC B cells expressed receptors for IL-4 and IL-5. Anti-CD40 mAb sustained the viability of GC B cells and IL-4 co-operated with anti-CD40 mAb for further enhancement of the cell viability. Anti-CD40 mAb and IL-4 were essential for inducing differentiation of GC B cells into antigen-specific IgG1-AFC and IL-5 efficiently enhanced their differentiation. GC B cells with the xid mutation responded for proliferation to CD40 ligation to a lesser extent and for the IgG1-AFC response to anti-CD40 mAb together with IL-4, but they showed impaired responsiveness to IL-5, regardless of enhanced expression of IL-5R in response to anti-CD40 mAb and IL-4. These results suggest that anti-CD40 mAb, IL-4 and IL-5 play a critical role in the differentiation of mouse GC B cells. The GC B cells from XID mice show a functional defect with respect to IL-5-mediated differentiation.

Animals↗
PubMed1997

Pilomatricoma with a bullous appearance.

A 15-year-old Japanese girl had an asymptomatic nodule on the right thigh of seven months' duration. The clinical appearance was similar to that of a bulla. There was a history of blunt trauma from dog scratch to the skin over the tumor shortly before tumor growth. Histopathological findings were consistent with pilomatricoma. In the overlying dermis, the collagen bundles were compressed to the tissue surrounding the tumor and the large space was seen. Around the tumor, some dilated endothelium-lined vascular channels were found, which were identified as lymphatic vessels.

Adolescent↗
PubMed1997

OK-432 therapy for recalcitrant warts.

Twelve patients with warts recalcitrant to various treatment, including cryotherapy, were treated with OK-432 injection therapy. Six patients received only subcutaneous injection, three received only intralesional injection, and the other three received both subcutaneous and intralesional injections. Complete clearing of the warts occurred in nine (75%) of 12 patients, while the other three patients were not cured. Grouping the patients by the method of injection, the success rate of subcutaneous injection was 5/9 (55.6%), and that of intralesional injection was 4/6 (66.7%). Although five patients complained of mild fever and malaise, these side effects gradually disappeared during the repeated injections. OK-432 injection is considered as a hopeful therapy for recalcitrant warts.

Adolescent↗
PubMed1997

Genomic diversity in the pfoA region of the theta-toxin-deficient strains of Clostridium perfringens.

The genomic structure of the pfoA-colA region in six theta-toxin-deficient strains of Clostridium perfringens was examined by Southern hybridization using the pfoR, pfoA, pbg, arcABDC and colA genes, encoding regulator for pfoA, theta-toxin, beta-galactosidase, arginine metabolism enzymes and kappa-toxin, respectively, as gene probes. It is suggested that the productivity of theta-toxin in these strains is diverse because of the multiple genetic backgrounds including single deletion of pfoA, large deletion of the pfoA-colA region and the putative point mutations.

Bacterial Toxins↗
PubMed1997

A case of contact dermatitis due to impurities of cetyl alcohol.

A 29-year-old man being treated for itchy lesions on the amputation stump of the thigh became allergic to betamethasone valerate and gentamicin sulfate cream (Rinderon VG). Closed patch tests with all the ingredients of the cream revealed positive reactions to cetyl alcohol 30% to 5% pet. Gas chromatographic analysis of the cetyl alcohol in the cream base detected stearyl alcohol (C18), myristyl alcohol (C14) and lauryl alcohol (C12) in addition to the main component of cetyl alcohol (C16). Patch testing with 99% pure analytical reagent grade saturated alcohols (C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20) showed negative reactions. Thus, it is concluded that some minor impurities in cetyl alcohol not detected by gas chromatography might be the cause of this dermatitis.

Adult↗
PubMed1996

Cross-linking of B cell antigen receptor-related structure of pre-B cell lines induces tyrosine phosphorylation of p85 and p110 subunits and activation of phosphatidylinositol 3-kinase.

To understand the function of B cell antigen receptor (BCR)-related complex on pre-B cells (pre-BCR, Vpre-B/lambda 5/mu heavy chain/Ig-alpha/Ig-beta), we examined pre-BCR- and BCR-mediated signaling events in human and mouse pre-B (Nalm-6, 697, NFS-5), immature B (IgM+ Daudi, WEHI-231) and mature B (IgM+ IgD+ BALL1) cell lines. Anti-mu cross-linking induced tyrosine phosphorylation of the cytoplasmic proteins in each cell type, but did not induce a detectable Ca2+ mobilization response in pre-B cells. While the pre-B cells expressed Syk protein at levels similar to those found in B cell lines, pre-BCR cross-linkage did not induce phosphorylation of Syk tyrosine residues. Different protein kinase C isozymes were expressed by pre-B (PKC-alpha), immature B (PKC-alpha and -beta) and mature B (PKC-beta) cell lines. Anti-mu cross-linking induced PKC translocation from the cytosolic to the membrane compartment in immature and mature B cells, but did not have this effect in a pre-B cell line. Anti-mu cross-linking induced tyrosine phosphorylation of the p85 and p110 subunits of phosphatidylinositol 3-kinase (P13-kinase) in both pre-B and B cell lines, but the pre-BCR induced P13-kinase activation was Syk independent. Ligation of the pre-BCR complex thus triggers a characteristic signaling pattern in pre-B cells.

Animals↗
PubMed1996

Successful treatment of molluscum contagiosum in the immunosuppressed adult with topical injection of streptococcal preparation OK-432.

A 37-year-old Japanese woman received an anticancer drug for 5 years following resection of mammary cancer and then developed widespread mollusca contagiosa, which we considered to be caused by immunosuppression induced by the chemotherapy. Because OK-432 (penicillin-treated and heat-treated lyophilized powder by a substrain of Streptococcus pyogenes A) was expected to be effective for immunosuppression, we tried its topical injection. The skin lesions disappeared almost completely within three months. OK-432 therapy is considered hopeful for treating viral skin diseases, even in immunosuppressed patients.

Adult↗