A novel HLA-B27 allele (B*2711) encoding an antigen reacting with both B27- and B40-specific antisera.
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Biomedical subjects
Publications and source records attributed to S Kondo.
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Chemical and biological studies were performed on lipopolysaccharide isolated from Selenomonas sputigena ATCC 33150T, a possible causative agent of periodontal diseases. The sugar components of the lipopolysaccharide of S. sputigena were mannose, galactose, glucose, L-glycero-D-mannoheptose (heptose), 2-keto-3-deoxy-octonic acid, glucosamine and galactosamine in a molar ratio of 0.3:1.0:1.0:1.0:0.2:3.0:3.2 (mol/mol heptose). Sephadex G-50 chromatography of the polysaccharide portion of the lipopolysaccharide obtained by partial hydrolysis yielded three fractions: the O-polysaccharide chain attached to the core oligosaccharide, the core oligosaccharide and monosaccharides. Compositional analysis of these fractions revealed that lipopolysaccharide of S. sputigena carries a short O-polysaccharide chain consisting of galactose and glucosamine and that the core oligosaccharide consisted of glucose, heptose, glucosamine and 2-keto-3-deoxyoctonic acid. It is of particular interest that galactosamine was detected as a component sugar of the lipid A moiety in addition to glucosamine, which is a usual component sugar of the lipid A of most gram-negative bacteria. Thus, the lipid A of S. sputigena might have a unique backbone that differs from that of the lipid A of other gram-negative bacteria. Lipid A of S. sputigena consisted mainly of fatty acids such as undecanoic, tridecanoic, tridecenoic, 3-hydroxytridecanoic and 3-hydroxytetradecanoic acid in a molar ratio of 0.4:1.0:0.3:4.0:0.5 (mol/mol tridecanoic acid). Lipopolysaccharide and lipid A from S. sputigena both exhibited biological activity in activating the clotting enzyme of Limulus amebocytes, the Schwartzman reaction, mitogenicity for murine lymphocytes and in inducing interleukin-1 alpha and interleukin-6 production in murine macrophages to the same extent as those observed for lipopolysaccharide of the Salmonella serovar typhimurium used as a positive control. The results suggested that the lipopolysaccharide of S. sputigena is a virulent factor in human periodontal diseases.
In order to examine whether saliva and breast-milk are mediators of the vertical transmission of hepatitis C virus (HCV) from an HCV carrier mother, serum, saliva, and breast-milk samples from 11 HCV carrier mothers were collected at the time of delivery, and at approximately 1- to 3-months intervals for as long as 30 months postpartum. Serum was also sampled from their children. All samples were analysed for the presence of HCV RNA, using the nested polymerase chain reaction method. No HCV RNA was detected in any breast-milk samples. In saliva, HCV RNA was detected in four of the 11 mothers (36%). These four mothers also had liver function abnormalities. Hepatitis C virus RNA was not detected in any serum samples of the children, and all children had normal liver function. The children were monitored for periods from 2 to 44 months. During this period, there was no evidence of virus transmission. Breast-milk is not likely to be a source of mother-to-child transmission of HCV. Maternal saliva may harbour HCV, but it may not result in infant infection.
Transforming growth factor-beta (TGF-beta) plays an important role not only in cell growth control but also in inflammation and immunoregulation. There are at least five different isoforms of TGF-beta. TGF-beta 1 has a large variety of biological functions including the modulation of inflammation and the immune system and has most extensively been studied in skin. Since ultraviolet B (UVB) is known to induce skin erythema and immunosuppression, we sought to examine whether UVB would alter the expression and production of TGF-beta 1 in normal human keratinocytes. Using reverse transcription-polymerase chain reaction (RT-PCR), constitutive expression of TGF-beta 1 mRNA was detected in keratinocytes and the level of TGF-beta 1 mRNA was increased 4 and 8 h after 300 J/m2 UVB irradiation. Production of TGF-beta 1 protein in culture supernatants assayed by ELISA was also increased at 24 h after irradiation. Cycloheximide treatment blocked this TGF-beta 1 protein induction indicating de novo protein synthesis of TGF-beta 1 from keratinocytes induced by UVB. These results suggest a possible role for TGF-beta 1 in UVB-induced skin inflammation and immunosuppression.
The permeation of ebiratide (H-Met(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8NH2), a novel ACTH analogue, across the intestinal mucosae has been examined by use of isolated intestinal membranes from rats in a modified Ussing chamber. Regional differences were observed in the permeation of ebiratide across intestinal membranes; the order of membrane permeability was jejunum > ileum > duodenum > colon. Overall, the permeation of ebiratide was relatively poor. The effects of various absorption enhancers were examined to increase the intestinal permeability to ebiratide. Sodium glycocholate and sodium caprate had no significant enhancing effect on the permeability of the jejunal membrane, but significantly enhanced the permeation of ebiratide through the colonic membrane. On the other hand, N-dodecyl-beta-D-maltopyramoside (LM) significantly enhanced the permeation of ebiratide through both jejunal and colonic membranes. In general, the absorption-enhancing effects of these agents were more predominant in the colon than in the jejunum. Membrane damage by the absorption enhancers was evaluated by measuring the amount of protein released from the intestinal membrane. It was found that all the absorption enhancers slightly increased the amount of protein released, but that the amounts of protein released in the presence of these enhancers were much less than in the presence of ethylenediaminetetraacetic acid (EDTA), used as a positive control. These findings suggest that the absorption enhancers, especially LM might be useful adjuvants for improving the intestinal absorption of peptide and protein drugs, including ebiratide.
To determine the prevalence of hepatitis C virus (HCV) infection in health care personnel in an HCV endemic area, we conducted a seroprevalence study of 1638 Kurume University Hospital physicians, nurses, laboratory staff, and clerical staff (560 men, 1078 women). Antibody to HCV (anti-HCV) was found in 2.8% (46) of subjects and hepatitis B surface antigen was found in 1.1% (18). The anti-HCV positive rate in health care personnel was no higher than reported in the general population of Fukuoka prefecture in Kyushu, Japan. There were no significant differences in anti-HCV positive rate by occupation. However, the prevalence of anti-HCV positive individuals increased significantly as age and length of time in an occupation increased. Anti-HCV positive rate in health care personnel was probably not related to length of time in an occupation. The data suggest that HCV infection is not easily transmitted to health care personnel in an HCV endemic area.
Three standard strains of Mycobacterium (M. tuberculosis H37Rv, M. avium ATCC15769 and M. kansasii ATCC12478) and 15 clinical isolates of Mycobacterium (7 M. tuberculosis, 2 M. avium, 3 M. kansasii, 1 M. intracellulare, 1 M. chelonae subsp. abscessus and 1 M. gordonae) were selected in order to study the bactericidal activities of povidone-iodine (PVP-I) drug substance and a commercially available PVP-I solution (Isodine solution) against Mycobacterium. After the bacilli had been exposed to the disinfectant solution at concentrations of 0.1 or 0.02% with 2% human serum for various incubation periods from 30 to 120 s, the PVP-I drug substance was inactivated by addition of 0.5% sodium thiosulfate. In the case of the commercially available PVP-I solution, a mixture of 10% Tween 80, 3% soybean lecithin and 0.5% sodium thiosulfate was used as inactivator. It was demonstrated that the 3 standard strains were completely inactivated within 30 s by 0.1% PVP-I drug substance and that the 15 clinical isolates were almost killed by 0.1% commercially available PVP-I solution within 60 s. As a result, the commercially available PVP-I product appeared to be a useful agent as disinfectant against all the tested species of Mycobacterium.
BACKGROUND AND PURPOSE: The origin and pathogenesis of cerebral aneurysms arising at nonbranching sites are not clear. Using our animal model to induce cerebral aneurysms in rats, we examined induced aneurysms that developed at nonbranching sites. METHODS: In 35 Sprague-Dawley rats, the left common carotid artery was ligated and renal hypertension was produced to induce cerebral aneurysms. Twelve months later, the circle of Willis was carefully examined under a dissecting microscope. RESULTS: Other than cerebral aneurysms at branching sites of the circle of Willis, aneurysmal bulges developing at nonbranching sites were found in the proximal portion of the posteriorice rebral artery (P1) on the side of carotid ligation, which supposedly acted as a major collateral pathway after the ligation, in 19 of 35 treated rats. A total of 30 lesions were found in these 19 rats, and they were classified into fusiform aneurysms (22 lesions) involving the entire vessel wall for a short distance and saccular aneurysms (8 lesions) involving only a part of the wall and expanding laterally from the vessel wall. These P1s became larger in caliber and more tortuous after ligation. Aneurysms developed more frequently in proportion to these changes in these vessels. Moreover, most aneurysms in these vessels developed at or near the curvatures. All of the lateral aneurysms were found on the lateral wall of the curvatures of the vessels. CONCLUSIONS: The present findings indicate that cerebral aneurysms at nonbranching sites and saccular aneurysms at branching sites can occur under the same etiologic conditions. The site of origin is strongly related to hemodynamic stress.
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Cone cells are lens-secreting cells in ommatidia, the unit eyes that compose the compound eye of Drosophila. Each ommatidium contains four cone cells derived from precursor cells of the R7 equivalence group which express the gene sevenless (sev). When a constitutively active form of Ras1 (Ras1V12) is expressed in the R7 equivalence group cells using the sev promoter (sev-Ras1V12), additional cone cells are formed in the ommatidium. Expression of Ras1N17, a dominant negative form of Ras1, results in the formation of 1-3 fewer cone cells than normal in the ommatidium. The effects of Ras1 variants on cone cell formation are modulated by changing the gene dosage at the canoe (cno) locus, which encodes a cytoplasmic protein with Ras-binding activity. An increase or decrease in gene dosage potentiates the sev-Ras1v12 action, leading to marked induction of cone cells. A decrease in cno+ activity also enhances the sev-Ras1N17 action, resulting in a further decrease in the number of cone cells contained in the ommatidium. In the absence of expression of sev-Ras1V12 or sev-Ras1N17, an overdose of wild-type cno (cno+) promotes cone cell formation while a significant reduction in cno+ activity results in the formation of 1-3 fewer cone cells than normal in the ommatidium. We propose that there are two signaling pathways in cone cell development, one for its promotion and the other for its repression, and Cno functions as a negative regulator for both pathways. We also postulate that Cno predominantly acts on a prevailing pathway in a given developmental context, thereby resulting in either an increase or a decrease in the number of cone cells per ommatidium. The extra cone cells resulting from the interplay of Ras1v12 and Cno are generated from a pool of undifferentiated cells that are normally fated to develop into pigment cells or undergo apoptosis.
The development and application of a new enzyme immunoassay for general assay of the Glycyrrhizae radix (GR) component in Chinese traditional medicines is described. Three commercial GR-based medicines, Tohoku kanzo (GRTK), Seihoku Kanzo (GRSEK) and Sinkyo kanzo (GRSK) were used as GR specimens. Anti-GRSK serum was elicited from rabbits immunized with GRSK fragments. The presence of common proteins as specific antigens of GR was first established by Western blot analysis of extracts of GRSK, GRSEK or GRTK using anti-GRSK. The specific antigens were applied to develop an ELISA for the assay of GR extract. Anti-GRSK was put in competition with a sample or standard GR extract and immobilized GRSK components in microtiter plate wells. The proportion of antibody binding to the solid-phase GRSK component was detected using an enzyme-labeled second antibody. The ELISA method was specific to GRSK extract and showed low sensitivity for the assay of GRTK extract. The technique of selected antibody enzyme immunoassay (SAEIA) was applied to develop a sensitive general assay method. Solid-phase GRTK extract, rather than immobilized GRSK extract, was used in the SAEIA. The SAEIA possessed the same quantitative working range of between 1 and 100 micrograms/ml for the assay of each extract of GRTK, GRSK and GRSEK. The SAEIA was successful in the detection and quantitative measurement of GR component contents in Chinese traditional medicines.
A new fuzzy immunoassay method generally applied to ten Glycyrrhizae Radix (GR) preparations of four different botanical origins was studied. Four kinds of antisera were elicited in rabbits immunized with GRs of different botanical origins. The presence of the characteristic GR protein (GRP) was shown using Western blot analyses and selected antibody enzyme immunoassay (SAEIA) methods. A GRP was isolated from one of the GR specimens which was selected using SAEIA methods. The isolated GRP was heated to reduce its binding activity to an anti-GR serum. A new fuzzy SAEIA method generally applicable for assay of the extract of the ten GR specimens was developed using heat-treated GRP as the solid-phase antigen. The fuzzy SAEIA method was successfully applied for the detection and quantitative analysis of the GR component contained in traditional Chinese medicines.
One of the enzymes from bakers' yeast that catalyzes the reduction of alpha- and beta-keto esters has been studied. The N-terminal amino acid sequence of the enzyme shows that the enzyme belongs to the aldo-keto reductase superfamily. The substrate specificity of the enzyme is broad and resembles those of other aldo-keto reductases. The enzyme catalyzes the reduction of keto esters, aldehydes, and aldohexoses.
Earlier studies demonstrated a correlation between diurnal bronchial variability and bronchial responsiveness (BR) in asthmatic patients. However, since the most severe bronchial obstruction tends to occur from midnight to early morning, diurnal bronchial variability might underestimate within-day bronchial variability. This study was undertaken to reevaluate the correlation after assessing more precisely the within-day variability of bronchial caliber in 43 children with episodic asthma (23 boys, 20 girls), aged 8-12 years. Seven FEV1 measurements were made every 4 h between 10:00 and 10:00 for 2 consecutive days. The coefficient of variation (CV) of the last six FEV1 was defined as the amplitude. Just after measurement of FEV1 at 10:00 on day 2, measurements of BR to house-dust allergen, histamine, and 7-min free running were made in 14, 14, and 15 patients, respectively. The BR was expressed as the percent change in FEV1 from the baseline value in house-dust inhalation and running challenges, and as the provocative concentration causing a 20% fall in FEV1 (PC20), transformed into a logarithmic scale, in histamine challenge. There were significant correlations between CV [mean (SD), 8.1 (5.3)%] and BR to house-dust [mean (SD), -19.0 (11.8)%] (r = -0.663, p < 0.01), and between CV [mean (SD), 7.4 (5.5)%] and histamine PC20 (geometric mean, 0.38 mg/ml) (r = -0.661, p = 0.01). There was a marginally significant correlation between CV [mean (SD), 6.4 (3.7)%] and BR to running [mean (SD), 28.5 (16.6)%] (r = -0.496, 0.05 < p < 0.1). These results confirmed the reliability of earlier studies that suggested that the bronchial variability may be one of clinical indices of BR to various stimuli in asthmatic patients.
The mechanism of fungitoxic action of an antifungal antibiotic benanomicin A was studied with intact cells and protoplasts of Saccharomyces cerevisiae as well as with its enzymic preparations. The results obtained are summarized as follows: (1) benanomicin A at relatively high concentrations (almost equal to MIC) was fungicidal and disrupted the cell permeability barrier, inducing leakage of intracellular K+ and ATP in growing cells, while the antibiotic had none of these effects in non-growing cells; (2) no biosynthesis of any of several major cellular constituents in yeast cells was inhibited markedly or selectively enough to explain its fungitoxic activity; (3) whereas benanomicin A induced lysis of metabolically active yeast protoplasts incubated in the presence of glucose, inactive yeast protoplasts incubated without glucose were refractory to the lytic action of the antibiotic; (4) osmotically shocked yeast cells became feasible to the cidal action of benanomicin A; (5) benanomicin A substantially inhibited uptake of 6-deoxy-glucose by yeast cells; (6) liposomes composed of phospholipids and cholesterol were not susceptible to benanomicin A; and (7) benanomicin A inhibited in vitro activity of H(+)-ATPase from yeast cell membranes to a greater extent than that for H(+)-ATPase from yeast mitochondria or H(+)-ATPase from yeast vacuolar membranes. Based on these and our previous data that benanomicin A preferentially binds to mannan or mannoproteins constituting the cell wall and cell membrane of yeasts, such binding of the antibiotic is suggested to deteriorate the normal structure and function of those cell membranes of yeasts which are in a growing or metabolically active state, ultimately leading to cell death.
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5,6-Dihydrobenzo[a]naphthacenequinone has been constructed by Diels-Alder reaction of an outer-ring diene with a naphthoquinone regioselectively. Similarly, the 14-hydroxy-5,6-dihydrobenzo[a]naphthacenequinone (13) has also been synthesized via the reaction of vinylketene acetal (11) with naphthoquinone.
The key intermediate tri-substituted alpha-tetralone (8) has been synthesized, either via tandem Michael addition-Dieckmann condensation reaction between dienolate and methyl crotonate in a low yield or via Barton's radical decarboxylation of diester (9) without 4-dimethylaminopyridine in 75% yield, and applied to the synthesis of the substituted 5,6-dihydrobenzo[a]naphthacenequinone.