[A case of primary biliary cirrhosis complicated with autoimmune hepatitis].
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Biomedical subjects
Publications and source records attributed to I Matsuo.
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The anterior part of the vertebrate head expresses a group of homeo box genes in segmentally restricted patterns during embryogenesis. Among these, Otx2 expression covers the entire fore- and midbrains and takes place earliest. To examine its role in development of the rostral head, a mutation was introduced into this locus. The homozygous mutants did not develop structures anterior to rhombomere 3, indicating an essential role of Otx2 in the formation of the rostral head. In contrast, heterozygous mutants displayed craniofacial malformations designated as otocephaly; affected structures appeared to correspond to the most posterior and most anterior domains of Otx expression where Otx1 is not expressed. The homo- and heterozygous mutant phenotypes suggest Otx2 functions as a gap-like gene in the rostral head where Hox code is not present. The evolutionary significance of Otx2 mutant phenotypes was discussed for the innovation of the neurocranium and the jaw.
Various manno-oligosaccharides including alpha-D-man-(1 --> 2)-D man and alpha-D-man-(1 --> 2)-alpha-D-man-(1 --> 2)-D-man were formed when a highly concentrated mannose solution was incubated in the presence of alpha-mannosidase from Aspergillus niger. alpha-D-Man-(1 --> 2)-D-man and alpha-D- man-(1 --> 2)-alpha-D-man-(1 --> 2)-D-man were isolated by activated carbon chromatography followed by high performance liquid chromatography using an amino-silica column. In addition to the above oligosaccharides, alpha-D-man-(1 --> 3)-D-man, alpha-D-man-(1 --> 6)-D-man, and alpha-D-man-(1 --> 2)-alpha-D-man-(1 -->6)-D-man were also isolated.
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A glycopeptide carrying a pentasaccharide core structure of asparagine-linked glycoproteins was synthesized. The synthesis of the carbohydrate part was performed starting from monosaccharide components in an unambiguous manner. The resultant pentaglycosyl azide was reduced into corresponding glycosyl amine and coupled with an aspartic acid derivative to furnish an Asn-linked oligosaccharide in a protected form. Subsequent coupling with a dipeptide, followed by deprotection gave the target compound.
To determine the therapeutic mechanism of PUVA in psoriasis vulgaris, the effects of PUVA on activated T lymphocytes were investigated in vitro. Peripheral blood mononuclear cells (PBMC) obtained from healthy volunteers were activated with Con A stimulation (Con A blasts). Both untreated PBMC and Con A blasts were irradiated with UVA light in the presence of 8-methoxypsoralen (8-MOP). The expressions of CD4, CD8, VLA-4 and LFA-1 of PBMC and Con A blasts were stained with each monoclonal antibody and the intensity of fluorescence was analyzed by FACScan. PUVA-treated PBMC showed decreased response to both Con A and PHA stimulation. PUVA treatment also suppressed the IL-2 production of Con A blasts and IL-2 response of PBMC with increasing UVA fluence. The expressions of LFA-1, VLA-4, CD4, CD8 and CD25 (IL-2R) molecules were decreased in PUVA-treated Con A blasts. Con A blasts were more sensitive than untreated PBMC to PUVA treatment. These results suggest that the therapeutic effects of PUVA on psoriasis vulgaris can be induced by suppression of the expression of cell surface molecules of activated T lymphocytes.
To determine the fundamental photochemical properties of new quinolones that can induce photosensitivity, the in vitro phototoxicity of these drugs (enoxacin, norfloxacin, ofloxacin, ciprofloxacin, and lomefloxacin) was examined with respect to photosensitizing ability to peroxidize unsaturated lipid squalene in ethanol solution. Lomefloxacin and ciprofloxacin showed the highest efficiency in sensitization of peroxidation of the lipid. Moderate repression of peroxidation occurred by addition of sodium azide (a quencher of singlet molecular oxygen), suggesting that the nonsinglet oxygen mechanism is operative in addition to the singlet oxygen mechanism.
Human red blood cells (RBCs) were lysed by in vitro irradiation in the presence of the antifungal drug griseofulvin (GF). Effects of UVA fluence and GF concentration on photohaemolysis were examined under aerobic conditions. The photohaemolysis occurred at much lower fluence than that necessary for oxidation of the membrane lipids. UVA-irradiated solution of GF did not cause haemolysis. The photohaemolysis was colloid osmotic in nature because it was preceded by K+ leakage from the cells and was delayed in the presence of 30 mM sucrose in the medium. Even under anaerobic conditions, RBCs were lysed by irradiation with higher fluence than that required for aerobic photohaemolysis. Therefore, some phototoxic mechanism other than photosensitized oxidation is also involved in the photohaemolysis.
An 84 bp element located between nucleotides -162 and -79 of the chicken alpha A-crystallin gene exhibits lens-specific enhancer activity. Transient transfection experiments using 5' deletion and linker scanner mutants has indicated that the 84 bp enhancer element is composed of three motifs, alpha CE1 (-162 to -134), alpha CE3 (-135 to -121) and alpha CE2 (-119 to -99). Neither alpha CE1 or alpha CE3 motif alone can exhibit enhancer activity even when trimerized, whereas together they can direct some degree of lens-specific expression. alpha CE2 alone shows low transcriptional activity when trimerized. A combination of alpha CE1 with alpha CE2 exerts full lens-specific enhancer activity comparable with that of the 84 bp enhancer element, indicating that alpha CE1 and alpha CE2 motifs are sufficient to confer lens-specific expression. Transcriptional activation by these two motifs from a distance required the additional presence of either or both motifs adjacent to the beta-actin basal promoter. Gel shift experiments indicated that the alpha CE1, alpha CE2 and alpha CE3 motifs specifically bind nuclear proteins. alpha CE1 binds a protein predominantly present in lens cells, whereas alpha CE2- and alpha CE3-binding proteins differ between lens and lung cells. Mutations within the alpha CE1 and alpha CE2 motifs that failed to bind nuclear factors in vitro resulted in loss of transcriptional activation, indicating that these nuclear factors play a key role in controlling lens-specific expression.
A lens-specific enhancer, an 84bp element between base pairs -162 and -79, of the chicken alpha A-crystallin gene is composed of two motifs, alpha CE1 (-162 and -134) and alpha CE2 (-119 and -99). Previous studies showed that a nuclear factor which binds to alpha CE1, termed alpha CEF1, is present at high levels in lens cells. Methylation interference analysis identified an inverted repeat of 5bp separated by 4bp, 5'-CTGGTTCCCACCAG-3', between positions -153 and -140 as an alpha CEF1-binding site. Gel mobility shift assays using synthetic oligonucleotides with site-directed mutations revealed that the alpha CEF1-binding consensus sequence is 5'-C(T/A)GGN6CC(A/T)G-3'. Comparison of this binding motif with regulatory sequences of diverse crystallin genes from diverse species suggests that alpha CE1 may be a ubiquitous crystallin gene enhancer.
A 46-year-old woman who presented with progressive facial hemiatrophy (PFH) following localized scleroderma is described. The patient had a markedly deformed and depressed plaque surrounded by erythema on the right cheek. She also showed linear scleroderma with hair loss on the occipital area and morphea lesions on the neck and shoulder. Histological findings of the facial and other atrophic lesions were consistent with localized scleroderma. Therefore, the PFH and localized scleroderma may have had the same pathological background in this case.
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Fluorospectroscopic behavior of chlorpromazine, mequitazine, afloqualone and piroxicam, which are known to induce skin photosensitivity, was examined in both homogeneous solutions and human buccal mucosal cells. Each drug showed large Stokes' shifts and their fluorescence intensities increased in hydrophobic solvents. These results indicated that the drugs tested can be used as hydrophobic fluorescence probes. Fluorescence microscopic observations of buccal mucosal cells treated with these drugs showed that all the drugs, especially chlorpromazine and mequitazine, were distributed in intracellular membranous regions.
We have characterized a regulatory region of the chicken alpha A-crystallin gene using transfection assays, which revealed that a 84 base pair element (-162 to -79) in the 5' flanking sequence is necessary and sufficient for lens-specific expression. A multimer of this element functions as lens-specific enhancer and synergistically activates transcription from chicken alpha A-crystallin or beta-actin basal promoters fused to the CAT gene. In vivo competition experiments demonstrated that DNA sequences containing the 84 bp element reduced alpha A-crystallin-CAT fusion gene expression. A nuclear factor present exclusively in lens cells binds to the 84 bp element in the region between positions -165 and -140. Southwestern blot analysis showed that 61,000 Mr (61 x 10(3) Mr) lens nuclear protein exhibited DNA-binding activity specific to the 84 bp element. Our data suggested that the 61 x 10(3) Mr nuclear protein, and the 84 bp element that it interacts with, may be involved in regulating the alpha A-crystallin gene expression in vivo.
UNLABELLED: A 25 years old man with psoriatic arthropathy complicated with clinical feature of ankylosing spondylitis was reported. 230 Japanese cases of psoriatic arthropathy were discussed. RESULT: 1) commoner in male 2) the cases that skin lesions were prior to arthritis and the cases that arthritis was prior to skin lesions were almost the same number 3) rheumatoid factor was seropositive in 17% of the cases 4) HLA-B27 was present in 9 of 50 cases and 7 of these 9 cases had central type arthritis 5) the cases had accompanied nail dystrophies in a high rate 6) concerning on skin lesion, many cases had atypical psoriatic lesion 7) 21.1% of the cases had central type arthritis 8) there were no certain effective therapy 9) prognosis of central type cases were relatively worse.
Griseofulvin-sensitized photo-oxidation of lipids was examined in vitro. Iodometric determination and thiobarbituric acid assay proved peroxidation of squalene, cholesterol and red blood cell membrane lipids by UVA irradiation in the presence of griseofulvin. Simultaneous progression of Type I (non-singlet oxygen) and Type II (singlet oxygen) processes is likely because the oxidation products of cholesterol through both processes were identified by thin layer chromatography. These results suggest that lipids, especially membrane lipids, are one of the possible targets for induction of griseofulvin photosensitivity.