Elevated levels of soluble Fas in systemic lupus erythematosus: comment on the article by Knipping et al.
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Biomedical subjects
Publications and source records attributed to H Ishida.
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Mice homozygous for an autosomal recessive mutation aly (alymphoplasia) lack both lymph nodes and Peyer's patches, and show defects in both humoral and cellular immunity. Histopathological analysis revealed chronic inflammatory changes in exocrine organs such as the salivary gland, lacrimal gland, and pancreas of the homozygotes (aly/aly), but not the heterozygotes (aly/+). In these exocrine organs, mononuclear cells consisting mainly of CD4+ T cells infiltrate periductal areas, and, in some cases, the cell infiltration extended to lobules. The inflammatory changes in exocrine organs were transferred by a T cell-enriched fraction of spleen cells from homozygous animals. These results suggest that autoimmune mechanisms mediated by self-reactive T cells may be involved in the inflammatory lesions of various exocrine organs in the homozygous mice, although these mice show immunodeficiency. Inflammatory changes were also observed in the lung of the homozygotes. Since Sjögren's syndrome is characterized by diffuse lymphocyte infiltration in the periductal areas of the lacrimal and salivary glands and is occasionally associated with pulmonary disease, aly/aly mice may serve as a unique spontaneous model of Sjögren's syndrome.
Amphiphilic lipid metabolites, including lysophosphatidylcholine (lysoPC) and long-chain acylcarnitine, accumulate in an ischemic myocardium and exert deleterious effects on membrane function. The effects of short-chain (3-carbon-chain, C3), medium-chain (C6 and C8), long-chain (C16) acylcarnitines, and lysoPC on the sodium current (INa) of isolated guinea-pig ventricular cells and on membrane fluidity and [14C]lysoPC uptake in cultured mouse embryo ventricular cells were examined. Guinea-pig ventricular cells were superfused with low-Na+(60 mM) Tyrode solution at a temperature of 32-33 degrees C. Ca2+ and K+ currents were blocked by external Co2+(3 mM) and internal Cs+(140 mM), respectively. Neither propionylcarnitine (PpC, C1) nor hexanoylcarnitine (HxoC. C6) at concentrations of 50, 100, 500 microM affected the amplitude of peak LNa, evoked by depolarizing pulses (0.5 Hz) to -20 mV from a holding potential of -100 mV. Octanoylcarnitine (OcoC, C8) (50 and 100 microM) did not alter the amplitude of peak INa while the highest concentration (500 microM) did inhibit it by 7.7 +/- 3.0% (mean +/- S.E., n = 6) significantly. Palmitoylcarnitine (PamC, C16) (1, 5, and 50 microM), decreased the amplitude of peak INa by 16.6 +/- 5.2% (n = 5), 36.1 +/- 4.3% (n = 11), and 52.7 +/- 8.8% (n = 4), respectively. LysoPC (50 microM) irreversibly depressed INa within 30 +/- 4 seconds (n = 4), and cell contracture occurred. If short- and medium-chain acylcarnitines would prevent the depressant effects of lysoPC on INa was then investigated. In the presence of PpC (100 microM) or HxoC (100 microM), the effects of lysoPC (either depression of INa or development of cell contracture) were not observed, while OcoC (100 microM) did not prevent any of these effects of lysoPC. In contrast, PpC and HxoC failed to prevent the reduction of INa caused by PamC. From these findings and membrane fluidity and [14C]lysoPC uptake studies, it was concluded that PpC exerts the protective effect by preventing the incorporation of lysoPC into phospholipid bilayers, and that short-chain acylcarnitine has a potent anti-amphiphilic effect against the amphipathic insults caused by lysoPC, whereas long-chain acylcarnitine had a potent amphiphilic effect; medium-chain acylcarnitine appeared to share both characteristics.
Involvement of PAF and kinin in the endotoxin (LPS)-induced hypotension was examined in the rat strains, Brown Norway (B/N);Kitasato (Normal) and B/N-Kitasato rats, intravenous injection of 10 mg/kg LPS caused a hypotension composed on two phases (15 min and 70 min after LPS injection). However in the kininogen-deficient B/N-Katholiek rats. LPS induced only the second phase. Pretreatment with bradykinin (BK) antagonist. Hoe 140 suppressed LPS-induced hypotension of normal rats to the level of Katholiek rats. TCV 309, a PAF-antagonist, suppressed the LPS-hypotension almost completely in the both strains. The reason why the PAF-antagonist showed almost complete inhibition, could be explained by a synergism. Because concomitant injection of a small amount of BK with PAF caused potentiation of the effect of the PAF action. These results suggest that formation of endogenous BK contributes mainly to the 1st phase of LPS-hypotension, and PAF contributes to both phases, by either direct and synergistic actions.
Hepatic angiomyolipoma is a rare tumor composed of spindle-shaped and epithelioid smooth muscle cells, adipose tissue, and proliferating blood vessels. We report the first documented case of this tumor developing in a patient with ulcerative colitis. A solitary tumor (7.5 x 7.5 x 7 cm) was detected in the left lateral segment of the liver and a left hepatic lobectomy was performed. The diagnosis of angiomyolipoma was confirmed by a pathological examination. We also review the literature on previously reported cases of hepatic angiomyolipoma.
Sialyl Lewis X ganglioside analogues containing 4-deoxy-, 6-deoxy-, and 4,6-dideoxy-D-galactopyranose in place of D-galactopyranose have been synthesized. Glycosylations of 2-(trimethylsilyl)ethyl 2,6-di-O-benzyl-beta-D-galactopyranoside and 2-(trimethylsilyl)ethyl beta-D-fucopyranoside with the phenyl 2-thioglycoside derivative of sialic acid, using N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid (TfOH) as the promoter in acetonitrile, gave the desired 2-(trimethylsilyl)ethyl sialyl-alpha-2-->3)-beta-D-galactopyranoside and -beta-D-fucopyranoside, respectively. The sialylgalactose derivative obtained was then modified to 4-deoxy and 4,6-dideoxy derivatives. These were converted, by O-benzoylation, transformation of the 2-(trimethylsilyl)ethyl group to trichloroacetimidates, and introduction of the methylthio group with methylthiomethylsilane, into the corresponding glycosyl donors, which were then coupled with 2-(trimethylsilyl)ethyl O-(2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl)-(1->3)-O-(2-acetamido-6-O- benzyl-2-deoxy-beta-D-glucopyranosyl)-(1->3)-2,4,6-tri-O-benzyl-beta-D- galactopyranoside in the presence of dimethyl(methylthio)sulfonium triflate (DMTST). The resulting pentasaccharides were each converted to the corresponding alpha-trichloroacetimidates, which, on coupling with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol, gave the desired sphingosine derivatives. Selective reduction of the azide group, N-acylation with octadecanoic acid, O-deacylation, and saponification of the methyl ester afforded the target compounds.
To examine a possible involvement of interleukin-10 (IL-10) in CD23/Fc epsilon RII expression in human monocytes, effects of IL-10 on the cell surface CD23 expression, soluble CD23 (sCD23) release, and CD23 type b mRNA expression were investigated. IL-10 suppressed IL-4-induced surface CD23 expression on monocytes in a dose-dependent manner, and this effect was completely neutralized by anti-IL-10 antibody. The suppressive effect of IL-10 on surface CD23 expression was not due to enhancement of sCD23 release from the cell surface because no increase in sCD23 in culture supernatant was detected after incubation with IL-10. Instead, the effect of IL-10 seemed to be exerted at the transcriptional level since IL-4-induced expression of CD23 type b mRNA was significantly reduced when IL-10 was present. Although IL-4 induced surface CD23 expression on both monocytes and B cells, the suppressive effect of IL-10 was observed only on monocytes, which underscores different regulatory mechanisms for CD23 expression between the two cell types.
Cytokine-inducers prevent insulin-dependent diabetes mellitus (IDDM) in animal models. We extend this therapy to non-insulin-dependent diabetes mellitus (NIDDM), because it was reported that diabetes of KK-Ay mice, a model for NIDDM, was recovered by allogenic bone-marrow transplantation that also prevented IDDM in animal models. An i.p. or i.v. injection of streptococcal preparation (OK-432) lowered fasting blood glucose (FBG) levels and markedly improved glucose tolerance test (GTT) in KK-Ay mice for more than 32 h regardless of the glucose loading routes (oral, i.v. or i.p.), while an i.v. injection of BCG improved FBG and GTT for more than 4 wks without body weight loss. The improvement of FBG and GTT with OK-432 was brought about in other NIDDM animals, GK rats and Wistar fatty rats. Among various cytokines possibly induced by OK-432 and BCG, IL-1 alpha, TNF alpha and lymphotoxin significantly improved FBG and GTT in KK-Ay mice, whereas IL-2 and IFN gamma did not. There were no differences between the OK-432-treated KK-Ay mice and control in histology of the pancreas, degree of insulin-induced decrease in blood glucose levels, and muscle glycogen synthase activities. As to insulin secretion, there is a tendency that the OK-432-treatment less that 1 week did not affect insulin levels during GTT, whereas the treatment more than 2 weeks increased the insulin levels. Thus, cytokine-inducers improved FBG and glucose tolerance of NIDDM animals probably via cytokines. The results imply a role of the cytokines in glucose tolerance of NIDDM, although precise immune and metabolic mechanisms remain to be elucidated.
Lipid-soluble polyether marine toxins were isolated from 80% methanol extract of oysters, Crassostrea gigas, harvested in 1993 at Tiki Road, Coromandel Peninsula, New Zealand, by chromatography on columns of LH-20 and ODS (C18), followed by reversed-phase high-performance liquid chromatography. They were identified as known brevetoxins, PbTx-2 and 3. PbTx-3 was also isolated from oysters collected at Rangaunu Harbour in February 1994 and June 1995, followed by the above procedures.
The effects of peroxynitrite (ONOO-) on cultured cardiac myocytes were examined by simultaneous measurements of intracellular Ca2+ ([Ca2+]i) and contractile function. On exposure to 0.2 mM ONOO-, [Ca2+]i increased to beyond the systolic level within 5 min with a concomitant decrease in spontaneous contraction of myocytes followed by complete arrest. Addition of a L-type Ca2+ channel blocker or removal of extracellular Ca2+ prevented the ONOO(-)-induced increase in [Ca2+]i, indicating that the increase in [Ca2+]i was caused by the enhanced influx of Ca2+ through the plasma membrane and not by the enhanced release from sarcoplasmic reticulum (SR). Plasma membrane fluidity and concentration of the thiobarbiturate acid-reactive substance (TBARS) in the cells remained unchanged by the ONOO- treatment. The complete cessation of contraction of myocytes persisted even under the massive increase in [Ca2+]i, which was induced by an additional saponin (5 microM) treatment. In conclusion, ONOO- increases [Ca2+]i in myocytes through disturbance of Ca2+ transport systems in the plasma membrane and impairs contractile protein.
A practical synthesis of the sialyl Lewis X (sLex) pentasaccharide, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta OEt (1), as a potential blocker for E-selectin has been described. The glycosylation of a trisaccharide acceptor, Fuc alpha (1-3)GlcNAc beta (1-3)Gal beta OEt, with a disaccharide donor, NeuAc alpha (2-3)Gal beta SMe, did not yield the desired sLex pentasaccharide 1 at all. However, the glycosylation of a disaccharide acceptor, GlcNAc beta (1-3)Gal beta OEt, with a disaccharide donor, NeuAc alpha (2-3)Gal beta SMe, quantitatively yielded the tetrasaccharide NeuAc alpha (2-3)Gal beta (1-4)GlcNAc beta (1-3)Gal beta OEt. This tetrasaccharide is readily converted to the title compound in a high yield by fucosylation, followed by deprotection. The inhibitory activities of compound 1 toward the binding of the natural ligand (sLex) with the E-, P-, and L-selectins were stronger than those of the sLex tetrasaccharide.
Sulfated sialyl Le(x) ganglioside analogues at C-6 of D-galactose, N-acetyl-D-glucosamine, and of both D-galactose and N-acetyl-D-glucosamine residues have been synthesized, in order to clarify the structure of the real carbohydrate ligand of L-selectin. Coupling of the suitably protected N-acetyl-D-glucosaminyl-beta (1-->3)-lactose derivatives 13 and 16 with the sialyl alpha(2-->3)-D-galactopyranosyl trichloroacetimidates 10 and 12 (glycosyl donors), via glycosylation of 2-(trimethylsilyl)ethyl 4,6-O-benzylidene-beta-D-galactopyranoside (1) with the phenyl 2-thioglycoside derivative (2) of N-acetylneuraminic acid (Neu5Ac) using N-iodosuccinimide/TfOH, O-benzoylation, removal of the benzylidene group affording 5, selective 6-O-levulinoylation, O-benzoylation, removal of the 2-(trimethylsilyl)ethyl group, and imidate formation, or via O-acetylation of 5, removal of the 2-trimethylsilyl)ethyl group, then imidate formation, gave the pentasaccharides 18-20. The glycosylation of the pentasaccharide acceptors (21-23) derived from 18-20 by removal of the 4-methoxybenzyl group, with phenyl 1-thioglycoside derivative 27 of L-fucose using dimethyl(methylthio)sulfonium triflate (DMTST) afforded the corresponding hexasaccharides 28-30, which were transformed in good yields, via reductive removal of their benzyl groups, O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, imidate formation, coupling with (2S,3R,4E)-2-azido-O-benzoyl-4-octadecene-1,3-diol (35) in the presence of boron trifluoride etherate, selective reduction of the azido group, coupling with octadecanoic acid, selective removal of the levulinoyl groups, treatment with sulfur trioxide-pyridine complex, then removal of the protecting groups, into the desired sulfated sialyl Le(x) ganglioside analogues 50-52.
No endoscopic follow-up studies are available on the development of diffuse antral vascular ectasia (DAVE). We present here a ten-year follow-up study from discrete initial lesions to the full picture of DAVE. In a 72-year-old female patient with liver cirrhosis, the earliest findings of DAVE were several red spots, with or without a white halo, in the distal antrum. During follow-up, the spots increased in number, coalesced, and extended to the proximal antrum. Three years after the initial findings, latent hemorrhage occurred at a time when confluent lesions were formed. One year later, diffuse distribution of the antral lesions was observed, which led to the diagnosis of DAVE and developed to the full picture within three more years. Two years later, the patient presented with hematemesis, which confirmed the diagnosis of DAVE clinically. Treatment consisted of monopolar electrocoagulation, leading to a stable hemoglobin value for one year. This case study provides some substantial clues to the early detection and treatment of DAVE.
The effect of growth conditions on the antibacterial activity of DU-6859a against Staphylococcus auerus, Escherichia coli, and Pseudomonas aeruginosa was compared with those of levofloxacin, sparfloxacin, and ciprofloxacin. This activity was not affected by different media, inoculum size or the addition of human serum, but was decreased under acidic conditions, in human urine, and in the presence of magnesium and ferrous ion, as were the other quinolones tested. Time-kill curve studies demonstrated the bactericidal action of DU-6859a against S. aureus, Streptococcus pneumoniae, E. coli, and P. aeruginosa. Morphological alteration of these bacteria after exposure to DU-6859a also demonstrated its bactericidal activity. The frequency of spontaneous resistance to DU-6859a was less than or equal to those of the reference drugs.
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Endothelin-1, a peptide isolated from vascular endothelial cells, facilitates the constriction of vascular smooth muscle and various pharmacological actions including vasodilation, the proliferation of smooth muscle cells and fibroblasts, and the stimulation of arachidonic acid metabolism. In this study, plasma, urine, and blister fluid endothelin-1 concentrations were determined in burn patients and changes in vasoactive substances derived from endothelial cells secondary to burns were investigated. Plasma endothelin-1 concentrations in burn patients were significantly lower than those in healthy individuals at rest. However, extremely high blister fluid endothelin-1 concentrations were observed within 30 hours of a burn. The amounts of endothelin-1 excreted in urine by burn patients over 24 hours also were higher than those in healthy individuals. The finding of high concentrations of endothelin-1 in blister fluids suggests that endothelin-1 is produced at wound regions in burn victims. Clinically, it appears that endothelin-1 is involved in circulation at the wound surface or in the healing of burns.
We analyzed the osteogenic capacity of the vascularized periosteum histologically and biochemically using a new experimental model of the vascularized tibial periosteum-hydroxyapatite composite in rats. Bone formation was observed not only on the surface but also in the pores of the hydroxyapatite at 4 weeks. The alkaline phosphatase activity increased to a peak at 2 weeks, with half this activity maintained until 8 weeks. The bone-specific bone gla protein content increased constantly as time passed. On the other hand, in the vascularized fascia-hydroxyapatite composite group (control group), no bone formation was observed histologically, alkaline phospatase activity was low, and bone gla protein content was very low. These results indicate that (1) the vascularized periosteum has the most significant osteogenic capaacity at 2 weeks, with a constant level of the activity maintained thereafter, (2) it forms new bone soon after operation, and (3) the amount of bone increases as time passes.
We report a case of acquired laryngomalacia in which airway obstruction due to prolapse of the epiglottis during inspiration was observed immediately after a unilateral mouth floor resection. Suggested causes are resection of unilateral elevator muscles of the hyoid bone, epiglottic oedema and transient loss of pharyngeal motor control due to surgical intervention and high-dose radiation.