Reactive arthritis or Reiter's syndrome and B51-associated seronegative spondyloarthropathy.
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Arthritis, Reactive↗
Biomedical subjects
S Ando
Publications and source records attributed to S Ando.
[A case of hypopituitarism and primary hypothyroidism associated with antiphospholipid syndrome].
Recent reports have indicated that antiphospholipid antibodies (aPL) are related to other clinical manifestations such as cardiac valve lesions and hemolytic anemia besides the major clinical features of antiphospholipid syndrome (APS), including thrombocytopenia, and recurrent fetal demise. We recently encountered a case of multiple hormonal deficiencies in the pituitary gland and hypothyroidism associated with an APS. Hypopituitarism of the patient had occurred after her delivery and a magnetic resonance imaging (MRI) examination disclosed "empty sella" of the hypophysis, so she was thought to have Sheehan's syndrome. There has been a few reports describing the relationship between aPL and endocrine disorders. aPL-related onset of these diseases may be more frequent than is generally appreciated.
Adult↗
Possible involvement of altered RGD sequence in reduced adhesive and spreading activities of advanced glycation end product-modified fibronectin to vascular smooth muscle cells.
Although fibronectin (FN) modified by advanced glycation end products (AGEs) has been shown to contribute to the development of diabetic vascular complications through its reduced adhesive activity to vascular cells, little is known about changes in the cell binding domain of AGE-modified FN. Here we examined the mechanism of reduced adhesive and spreading activities of AGE-modified FN to vascular smooth muscle cells (SMCs), particularly the contribution of modification of Arg-Gly-Asp (RGD) sequence. Incubation with glucose caused not only the formation of N(epsilon) -carboxymethyllysine and pentosidine, but also polymerization of FN in a dose- and time-dependent manner. AGE-modified FN had significantly low adhesive and spreading activities to cultured SMCs. On the other hand, multimeric FN formed by disulfide bonds did not show any effect on either cell adhesion or spreading. The adhesive activity of type I collagen, one of the RGD sequence-containing proteins, to SMCs also decreased by AGE-modification. The inhibitory effect of AGE-modification on cell adhesion was significantly greater in type I collagen than in FN. Although the extent of AGE-modification of type I collagen was indistinguishable from that of FN, AGE-modification decreased the arginine content of type I collagen by 69.5% and of FN by 30.6%, compared with their non-glycated forms. The addition of RGD peptides caused a decrease in adhesion of SMCs to non-glycated FN, but not to AGE-modified FN. Modification of RGD sequence with glyoxal eliminated its inhibitory effect on cell adhesion. Our results suggest that a marked decrease in adhesive and spreading activities of AGE-modified FN to SMCs might largely be due to a modification of its RGD sequence by AGE, thus suggesting a potential link between AGE modification of FN and the pathogenesis of diabetic angiopathy.
Amino Acids↗
Causal relationship between conformational change and inhibition of domain functions of glycoxidative fibronectin.
Glycoxidative modification of various body proteins, including fibronectin (FN), has been shown to change their structural and functional properties, and be implicated in pathogenesis of diabetic complications. Little is known about the role of secondary structure of glycoxidative FN (gFN) in its domain functions. gFN was prepared by incubation with 25 and 200 mM glucose in 0.2 M sodium phosphate buffer at 37 degrees C on a shaking plate under aerobic and sterile conditions for various time intervals up to 49 days, being defined as gFN25 and gFN200, respectively. Unmodified FN (uFN) was prepared by incubation in 0.2 M sodium phosphate buffer without any glucose at 4 degrees C for 49 days. The extent of glycoxidative modification was examined using a noncompetitive enzyme-linked immunosorbent assay with an antibody against N(epsilon) -(carboxymethyl)lysine (CML), one of the major glycoxidation products. The binding activities of uFN and gFN to collagen, gelatin and heparin were determined by a solid phase enzyme immunoassay or heparin-affinity HPLC. Cell attachment was estimated by the extent of adhesion of FITC-labeled smooth muscle cells to uFN or gFN. Conformational change in gFN was detected by SDS-polyacrylamide gel electrophoresis and spectroscopy (circular dichroism). CML was detected in gFN25 and gFN200 after 49 and 21 days of incubation, respectively. Levels of CML were about six-fold higher in gFN200 than in gFN25 after 49 days. Both gFN25 and gFN200 showed a significant decrease in the ability of binding to collagen and gelatin after 7 days of incubation. The binding activity for heparin was significantly decreased in both gFN25 and gFN200 after one day. Cell attachment activity was reduced to 89% and 76% of the unmodified form in both gFN25 and gFN200 after 49 days, respectively. High molecular weight materials were found in gFN25 and gFN200 after 21 and 7 days, respectively. CD spectrum showed that gFN25 had lost its native conformation after 3 days of incubation, depending upon the concentration and incubation interval of the applied glucose. These in vitro results suggest that the loss of native conformation may reduce the domain functions of gFN, including binding activity to macromolecular ligands and cell attachment, and may play a major role in the pathogenesis of diabetic complications.
Cell Adhesion↗
[Antiphospholipid antibody-associated hemophagocytic syndrome].
Autoimmune diseases such as systemic lupus erythematosus (SLE) are known to be causative disorders of reactive hemophagocytic syndrome (HPS). We recently encountered a case of HPS associated with the presence of antiphospholipid antibodies (aPL). This patient showed severe thrombocytopenia (0.2 x 10(4)/microliter) and moderate anemia (Hb; 7.6 g/dl). Bone marrow smears showed normal cellularity and an increase in mature-looking histiocytes scattered among the hematopoietic cells, which accounted for approximately 3% of all nucleated cells and were distributed unevenly. These cells showed marked phagocytosis of hematopoietic cells, including megakaryocytes, erythroblasts, and a few neutrophils. In this patient, there is no possible causative factor of HPS (such as viral infection, lymphoma, and systemic lupus erythematosus) except the presence of aPL. There have been no previously reported cases describing the relationship between aPL and HPS. This case indicate that attention should be given to the possibility that certain patients with aPL-associated cytopenia may display accompanying intramedullary hemophagocytic phenomena.
Adult↗
Intestinal fatty acid binding protein gene expression reveals the cephalocaudal patterning during zebrafish gut morphogenesis.
Intracellular fatty acid-binding proteins (FABPs) are small and highly conserved cytoplasmic proteins that bind long-chain fatty acids and other hydrophobic ligands. We have examined, as a model for studying intestinal epithelial cell differentiation, the cell-specific and spatio-temporal expression of intestinal fatty acid-binding protein (i-fabp) gene during zebrafish larval development. After molecular cloning of zebrafish I-FABP cDNA, whole-mount in situ hybridization analysis revealed that i-fabp is expressed in the intestinal tube around day 3 postfertilization. By day 4, highest level of i-fabp transcript is encountered in the proximal columnar epithelium. From day 5 onwards, i-fabp is strongly expressed in the anterior intestine and its rostral expansion, slightly expressed in the esophagus mucosa and rectum, while no mRNA could be detected in the posterior intestine. Therefore, the regional differentiation of the intestine precedes first feeding and complete yolk resorption. I-fabp expression in the anterior intestine of the fed larvae is correlated with an intracellular storage of lipid droplets in the enterocytes and the massive synthesis of very low-density lipoprotein particles. In conclusion, the cephalocaudal expression pattern of i-fabp demarcates early during zebrafish gut morphogenesis the anterior fat absorbing to posterior cells of the intestine. This gene could be used as a marker for screening for mutations that affect the events of intestinal epithelial differentiation, cephalocaudal patterning, and asymmetric gut looping morphogenesis.
Amino Acid Sequence↗
[Acute and chronic renal failure].
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Acute Kidney Injury↗
SHC-alpha5beta1 integrin interactions regulate breast cancer cell adhesion and motility.
The oncogenic SHC proteins are signaling substrates for most receptor and cytoplasmic tyrosine kinases (TKs) and have been implicated in cellular growth, transformation, and differentiation. In tumor cells overexpressing TKs, the levels of tyrosine phosphorylated SHC are chronically elevated. The significance of amplified SHC signaling in breast tumorigenesis and metastasis remains unknown. Here we demonstrate that seven- to ninefold overexpression of SHC significantly altered interactions of cells with fibronectin (FN). Specifically, in human breast cancer cells overexpressing SHC (MCF-7/SHC) the association of SHC with alpha5beta1 integrin (FN receptor) was increased, spreading on FN was accelerated, and basal growth on FN was reduced. These effects coincided with an early decline of adhesion-dependent MAP kinase activity. Basal motility of MCF-7/SHC cells on FN was inhibited relative to that in several cell lines with normal SHC levels. However, when EGF or IGF-I was used as the chemoattractant, the locomotion of MCF-7/SHC cells was greatly (approx fivefold) stimulated, while it was only minimally altered in the control cells. These data suggest that SHC is a mediator of the dynamic regulation of cell adhesion and motility on FN in breast cancer cells.
Adaptor Proteins, Signal Transducing↗
Isolation and characterization of novel neutral glycolipids from Thermoplasma acidophilum.
Several novel neutral glycolipids (GL-1a, GL-1b, GL-2a, GL-2b and GL-2c) were isolated from Thermoplasma acidophilum by high-performance liquid chromatography using phenylboronic acid-silica and preparative thin-layer chromatography. The tentative structures of these lipids were characterized by the combination of gas-liquid chromatography, the methylation procedure, and (1)H-NMR and FAB-mass spectrometries. The lipophilic portion of the neutral glycolipids was composed of a simple molecular species named caldarchaeol (dibiphytanyl-diglycerol tetraether). The sugar moieties of these glycolipids were composed of gulose and glucose which formed monosaccharide residues on one side or both sides of the core lipids. Gulose was attached to the terminal glycerol OH group of the core lipid with a beta-configuration and glucose being attached with an alpha-configuration. The proposed structure of GL-1a was gulosylcaldarchaeol and that of GL-1b was glucosylcaldarchaeol. The structures of GL-2a, GL-2b, and GL-2c were the analogs of the caldarchaeol derivatives attached by a variety of gulosyl residues or glucosyl residues on both sides of the terminal OH groups.
Carbohydrates↗
Age-changes of brain synapses and synaptic plasticity in response to an enriched environment.
Numerical synaptic density and synaptic vesicle density in rat frontal cortex were examined by electron microscopy as a function of age. The density of axospinous synapses, a major population of synapses, was found to peak at age 1 month, and to gradually decrease with aging. The synaptic vesicle density in axospinous synapses was shown to rapidly increase to a peak during the first 3 weeks and then decrease to the adult level, which remained unchanged in senescence. The time course of synaptic changes in aging is presented in this study. In a previous report (Saito et al. [1994] J. Neurosci. Res. 39:57-62), we showed that enriched rearing conditions restored the age-related decrease of synaptophysin contents. This might be due to increased numerical synaptic density or enhanced packing density of synaptic vesicles in synapses. The results of the present study support the latter explanation; that is, synaptic vesicle contents were increased without changes in synaptic density. Synaptic plasticity induced by environmental stimulation is shown to relate with synaptic strengthening, but not with the formation of new synapses.
Aging↗
Effect of atrial natriuretic peptide on muscle sympathetic activity and its reflex control in human heart failure.
BACKGROUND: The purpose of this study was to determine if atrial natriuretic peptide (ANP) exerts a relative inhibitory effect on muscle sympathetic nerve activity (MSNA) at rest and during nonhypotensive lower body negative pressure (LBNP) in heart failure, as in healthy subjects. METHODS AND RESULTS: Fifteen men (age 39+/-2 years [mean+/-SE]) with dilated cardiomyopathy (ejection fraction 18+/-3%) received intravenous ANP (50 microgram bolus, then 50 ng. kg-1. min-1) and nitroglycerin (NTG, 8 mg/min) as a hemodynamic control. During each infusion MSNA, blood pressure (BP), central venous pressure (CVP), and heart rate (HR) were recorded before and during LBNP at -6 and -12 mm Hg. NTG and ANP caused similar and significant reductions in CVP and diastolic BP, but resting MSNA did not increase with either infusion. LBNP at -6 mm Hg lowered CVP (P<0.05), whereas LBNP at -12 mm Hg caused significant reductions in CVP, systolic BP, and diastolic BP. These effects of nonhypotensive and hypotensive LBNP on CVP and BP were similar during ANP and NTG infusions, yet MSNA was lower both before and with LBNP during ANP (P<0.02). Nonhypotensive LBNP increased MSNA during NTG (+133+/-68 Units; P<0.001) but not during ANP infusion (+24+/-23 Units; P=NS). CONCLUSIONS: These observations are consistent with the concept that ANP exerts a sympathoinhibitory action in heart failure. This is most evident in response to reductions in atrial pressures that do not affect systemic BP.
Adult↗
Insulin receptor substrate 1 is a target for the pure antiestrogen ICI 182,780 in breast cancer cells.
The pure antiestrogen ICI 182,780 inhibits insulin-like growth factor (IGF)-dependent proliferation in hormone-responsive breast cancer cells. However, the interactions of ICI 182,780 with IGF-I receptor (IGF-IR) intracellular signaling have not been characterized. Here, we studied the effects of ICI 182,780 on IGF-IR signal transduction in MCF-7 breast cancer cells and in MCF-7-derived clones overexpressing either the IGF-IR or its 2 major substrates, insulin receptor substrate 1 (IRS-1) or src/collagen homology proteins (SHC). ICI 182,780 blocked the basal and IGF-I-induced growth in all studied cells in a dose-dependent manner; however, the clones with the greatest IRS-1 overexpression were clearly least sensitive to the drug. Pursuing ICI 182,780 interaction with IRS-1, we found that the antiestrogen reduced IRS-1 expression and tyrosine phosphorylation in several cell lines in the presence or absence of IGF-I. Moreover, in IRS-1-overexpressing cells, ICI 182,780 decreased IRS-1/p85 and IRS-1/GRB2 binding. The effects of ICI 182,780 on IGF-IR protein expression were not significant; however, the drug suppressed IGF-I-induced (but not basal) IGF-IR tyrosine phosphorylation. The expression and tyrosine phosphorylation of SHC as well as SHC/GRB binding were not influenced by ICI 182,780. In summary, downregulation of IRS-1 may represent one of the mechanisms by which ICI 182,780 inhibits the growth of breast cancer cells. Thus, overexpression of IRS-1 in breast tumors could contribute to the development of antiestrogen resistance.
Breast Neoplasms↗
Thermostable aminopeptidase from Pyrococcus horikoshii.
From the genome sequence data of the thermophilic archaeon Pyrococcus horikoshii, an open reading frame was found which encodes a protein (332 amino acids) homologous with an endoglucanase from Clostridium thermocellum (42% identity), deblocking aminopeptidase from Pyrococcus furiosus (42% identity) and an aminopeptidase from Aeromonas proteolytica (18% identity). This gene was cloned and expressed in Escherichia coli, and the characteristics of the expressed protein were examined. Although endoglucanase activity was not detected, this protein was found to have aminopeptidase activity to cleave the N-terminal amino acid from a variety of substrates including both N-blocked and non-blocked peptides. The enzyme was stable at 90 degrees C, with the optimum temperature over 90 degrees C. The metal ion bound to this enzyme was calcium, but it was not essential for the aminopeptidase activity. Instead, this enzyme required the cobalt ion for activity. This enzyme is expected to be useful for the removal of N(alpha)-acylated residues in short peptide sequence analysis at high temperatures.
Aminopeptidases↗
Analysis of cross-polarization dynamics between two abundant nuclei, (19)F and (1)H, based on spin thermodynamics theory
The phenomenological theory of spin thermodynamics based on the spin temperature hypothesis was employed to describe the cross-polarization (CP) dynamics between two abundant nuclei, (19)F and (1)H, when the number of fluorine atoms is not substantially less than the number of hydrogens. The influence of T(1rho)'s of both nuclei and the relative magnitude (heat capacity) of the two spin baths must be incorporated explicitly into the analysis in order to derive values for the parameters involved in the CP dynamics. Numerical calculations were performed to clarify the difference in the evolution of magnetization in variable contact time CP experiments between the (1)H --> (13)C and (1)H --> (19)F cases. A new type of CP-drain experiment was developed for observing the residual (1)H magnetization after (1)H --> (19)F CP. (19)F direct polarization magic-angle spinning (MAS), (1)H --> (19)F CP, and (1)H --> (19)F CP-drain MAS NMR spectra have been measured for a fluorinated polyimide, 6FDA/ODA. The CP dynamics between (1)H and (19)F for the polyimide were analyzed on the basis of the spin thermodynamics theory. The constant for polarization transfer (T(HF)) was determined by the analysis using the effective CP parameters, which were directly obtained from the CP and CP-drain experiments, together with independently measured values of T(H)(1rho) and T(F)(1rho). Copyright 1999 Academic Press.
Journal Article↗
Susceptibility to oxidation of copper-induced plasma lipoproteins from Japanese eel: protective effect of vitellogenin on the oxidation of very low density lipoprotein.
The susceptibility to oxidation of copper-induced plasma lipoproteins from Japanese eel Anguilla japonica was examined with the guidance of thiobarbituric acid-reactive substances (TBARS). The TBARS values of copper-induced plasma lipoproteins increased with increasing the lipid-to-apolipoprotein ratios and very low density lipoprotein (VLDL) exhibited the highest TBARS value. On the other hand, vitellogenin, estrogen-induced precursor of egg yolk proteins, was resistant to copper-induced oxidation and seemed to chelate low concentrations of copper ion. Vitellogenin also protected the copper-induced oxidation of VLDL because of its antioxidant function. Vitellogenin seemed to serve as transition metals-binding lipoprotein by which free-radical reactions in the oocytes were extensively depressed.
Anguilla↗
Cerebral blood flow and oxygen metabolism during cardiopulmonary bypass with moderate hypothermic selective cerebral perfusion.
Cerebral blood flow was measured using transcranial doppler during cardiopulmonary bypass in nine patients with selective cerebral perfusion for surgery of arch aorta (group S). For comparison, 11 adult open heart patients (group C) were also measured. The authors' selective cerebral perfusion at 28 degrees C resulted in moderate hypothermia and antegrade perfusion using independent pumps for three branches. Total flow in the three branches was 500 ml/min. A Labodop DP-100 doppler ultrasound velocimeter was used to measure middle cerebral arterial blood flow velocity. Hemoglobin concentration and oxygen saturation were also measured in arterial and jugular venous blood. The arteriovenous oxygen content difference (Ca-vO2) was calculated and multiplied by the middle cerebral arterial blood flow velocity value, which resulted in the cerebral metabolic rate for oxygen (CMRO2). The cerebral perfusion pressure of group S was lower than in group C, and the arterial carbon-dioxide tension (PaCO2) of group S was higher than in group C during cardiopulmonary bypass. Middle cerebral arterial blood flow velocity values of both groups remained constant before, during and after cardiopulmonary bypass. The CMRO2 decreased during cardiopulmonary bypass and showed no difference between the two groups. The changes in PaCO2 might be significant factors in the increase in cerebral blood flow during selective cerebral perfusion. This study supports the conclusion that, compared with our routine open heart surgery procedures, our selective cerebral perfusion procedures had the same cerebral blood flow and oxygen metabolism during cardiopulmonary bypass.
Adult↗
PLGA microspheres containing plasmid DNA: preservation of supercoiled DNA via cryopreparation and carbohydrate stabilization.
Biodegradable microspheres containing plasmid DNA have potential uses as mediators of transfection in cells, particularly phagocytic cells such as macrophages. However, the hydrophilic nature and the structural instability of supercoiled DNA preclude its facile encapsulation in polymer matrixes such as poly(d, l-lactic-co-glycolic acid) (PLGA) by traditional methods. We initially studied the microencapsulation of plasmid DNA using the established water-in-oil-in-water double-emulsion solvent-evaporation method and found that (1) the encapsulation efficiency was low (about 20%), (2) the microencapsulation procedure nicked (degraded) the supercoiled DNA, and (3) lyophilization of the microsphere also nicked the DNA. We have therefore designed a new microsphere preparation method (called cryopreparation) to specifically address these concerns. Using the cryopreparation method, the aqueous phase of the primary emulsion containing the plasmid DNA is frozen and then subjected to homogenization. Because there is no shear stress inside a solid, we hypothesized that freezing the aqueous phase of the primary emulsion would help to preserve the supercoiled plasmid DNA during formation of the secondary emulsion. We also hypothesized that the formation of crystals from buffers within the primary emulsion was a causative factor for nicking during freezing or lyophilization, and that disruption of the crystal formation by the addition of saccharides into the primary emulsion would improve the supercoiled-DNA content of the spheres. Our results support the two hypotheses. Not only was the supercoiled-DNA content increased from 39% to over 85%, but the encapsulation efficiency was also elevated from 23% to over 85%.
Carbohydrates↗
Total synthesis of a cholinergic neuron-specific ganglioside GT1a alpha: a high affinity ligand for myelin-associated glycoprotein (MAG).
An efficient total synthesis of a cholinergic neuron-specific ganglioside GT1a alpha (IV3NeuAcIII6NeuAcII3NeuAc-GgOse4Cer) is described. The suitably protected sialyl-alpha(2-->6)-gangliotriose (III6NeuAc-GgOse3) derivative was glycosylated with the phenyl 2-thioglycoside of sialic acid in the presence of N-iodosuccinimide (NIS) and trimethylsilyl trifluoromethane-sulfonate (TMSOTf) in acetonitrile medium, giving the disialogangliotriose (III6NeuAcII3NeuAc-GgOse3) derivative which contains both sialyl-alpha(2-->6)-GalNAc and sialyl-alpha(2-->3)-Gal structures (Route I). This pentasaccharide was efficiently synthesized also by the coupling of (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto -2-nonulopyranosylonate)-(2-->6)-2-deoxy-3,4-O-isopropylidene-2-ph thalimido-D-galactopyranosyl trichloroacetimidate with 2-(trimethylsilyl)ethyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto -2-nonulopyranosylonate)-(2-->3)-(2,6-di-O-benzyl-beta-D-galactopy ranosyl)-(1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside, followed by conversion of the phthalimido group to the acetamido group (Route II). O-Deisopropylidenation and further glycosylation with methyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-gala ct-2-nonulopyranosylonate)-(2-->3)-2,4,6-tri-O-benzoyl-1-thio-b eta-D-galactopyranoside, promoted by dimethyl(methylthio)sulfonium triflate (DMTST), gave the desired trisialogangliotetraose (IV3NeuAcIII6NeuAcII3NeuAc-GgOse4) derivative, which was converted stepwise into the title ganglioside GT1a alpha by the introduction of the ceramide part and then complete deprotection. The ganglioside obtained was shown to be identical with the native GT1a alpha on TLC-immunostaining.
Animals↗