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K Furuichi

Publications and source records attributed to K Furuichi.

At least 55 records · Page 3Linked to original sources

In situ expression and soluble form of P-selectin in human glomerulonephritis.

To clarify the early involvement of cellular adhesion molecules in human glomerulonephritis, we investigated P-selectin and high endothelial venules' (HEVs) marker MECA-79 expression in kidney specimens by immunohistochemical and in situ hybridization analyses, and measured serum and urinary soluble P-selectin levels by enzyme-linked immunosorbent assay. In normal controls, P-selectin and MECA-79 expression were negative in glomeruli (N = 4), and serum soluble P-selectin levels were 114.3 +/- 36.8 ng/ml (mean +/- SEM, N = 12). Soluble P-selectin was not detectable in urine of all cases. In proliferative glomerulonephritis involving rapidly progressive glomerulonephritis (N = 6), IgA nephropathy (N = 26), lupus nephritis (N = 7) and acute glomerulonephritis (N = 2), both glomerular and interstitial P-selectin expression were up-regulated. Glomerular P-selectin expression correlated positively with local cellular accumulation, endocapillary proliferation and CD41b (platelet) staining. Interstitial P-selectin expression showed a positive correlation with the grade of local cellular infiltrates. P-selectin mRNA signals detected by in situ hybridization were only observed on capillary or venous endothelium in the interstitium, but not in glomeruli. In addition, MECA-79 was expressed on the plump endothelial cells at the cortico-medullary junction (outer medulla). Serum soluble P-selectin levels were significantly higher in patients with proliferative glomerulonephritis, especially in glomerular and interstitial P-selectin positive staining, and correlated with glomerular endocapillary proliferation. These observations suggested that P-selectin was associated with both glomerular and interstitial leukocyte accumulation in human glomerulonephritis, and might be expressed by two distinct mechanisms that are the activated platelets in glomeruli and the de novo expression in the interstitial lesions that correlated with MECA-79 expression as HEVs like vessels, and serum soluble P-selectin may be a useful marker for predicting in situ P-selectin expression associated with glomerular endocapillary proliferation in nephritis.

Adult↗

Glomerular ICAM-1 expression related to circulating TNF-alpha in human glomerulonephritis.

To clarify the in vivo involvement of cellular adhesion molecules and cytokines in human glomerulonephritis, we have investigated the glomerular and interstitial expression of intercellular adhesion molecule 1 (ICAM-1) in 69 kidney biopsy specimens by immunohistochemical methods and its correlation with serum bioactive tumor necrosis factor alpha (TNF-alpha) and soluble ICAM-1 (sICAM-1) levels in 43 cases. In normal controls, glomerular ICAM-1 expression and serum TNF-alpha and sICAM-1 levels showed a mean score of 1.0 (n = 7) and were 12.1 +/- 1.5 and 187 +/- 5 ng/ml (mean +/- SEM, n = 25), respectively. ICAM-1 was positive in 68 kidneys except in 1 patient with membranous nephropathy at various degrees in glomeruli and in 72% of peritubular capillaries or venules in the interstitium. Serum-bioactive TNF-alpha levels increased in the patients with IgA nephropathy, purpura nephritis, and lupus nephritis (LN) (18.9 +/- 4.1, 32.6 +/- 13.3, and 20.9 +/- 3.5 pg/ml) and were positively correlated with the grade of glomerular ICAM-1 expression (n = 43, r = 0.57, p < 0.001), endocapillary proliferation with exudative lesions (r = 0.72, p < 0.001) and hematuria (r = 0.62, p < 0.001). Serum sICAM-1 levels were elevated in patients with LN and purpura nephritis and decreased from 312 +/- 40 to 226 +/- 21 ng/ml after methylprednisolone pulse therapy in LN (n = 9, p = 0.0285). sICAM-1 levels were positively correlated with the grade of interstitial ICAM-1 expression (r = 0.46, p < 0.05), and sICAM-1 levels (>210 ng/ml) showed high odds ratios in the interstitial ICAM-1-positive cases and systemic vasculitides such as purpura nephritis and LN (6.00, p = 0.0355; 6.50, p = 0.0216, respectively). These results suggest that bioactive TNF-alpha might relate to glomerular ICAM-1 expression associated with endocapillary lesions in human glomerulonephritis and that sICAM-1 levels may be used as a clinical marker to assess interstitial lesions in human nephritis and systemic vasculitides.

Adolescent↗

Horseshoe lung: demonstration by electron-beam CT.

Horseshoe lung is a rare pulmonary anomaly characterized by fusion of the posterobasal portions of the right and left lungs behind the pericardial reflection, anterior to the aorta. The majority of reported cases occur in conjunction with scimitar syndrome, including hypoplasia of the right lung, anomalous right pulmonary venous return and systemic arterial supply to the lung. Horseshoe lung is usually diagnosed on pulmonary arteriography when the right inferior pulmonary artery crosses the midline and extends to the left lung base. Bronchography is also diagnostic when the branch of horseshoe portion arises from the right bronchus and passes within the lung parenchyma to midline of the lung tissue. The only described CT finding of horseshoe lung is the contiguity of the right and left lungs behind the heart. Most cases are infants under 12 months of age and CT images are severely hampered by respiration motion artefacts. Such artefacts are minimized by using electron-beam computed tomography, allowing a more detailed CT appearance of horseshoe lung in this case.

Child, Preschool↗

[Quantification of brain perfusion SPECT with N-isopropyl-p-iodoamphetamine using noninvasive microsphere method: estimation of arterial input by dynamic imaging].

We have developed a noninvasive method to quantify brain perfusion SPECT with 123I-N-isopropyl-p-iodoamphetamine (IMP) using serial dynamic planar imaging of the initial transit phase. The method is based on the microsphere model, but does not require arterial sampling. Serial dynamic planar imaging was performed for 6 min after the bolus injection of IMP (167 MBq in 1.5 ml), followed by additional planar imaging at 20 min and SPECT scan thereafter. The total arterial input to the brain during the initial 5 min after injection was estimated by the injected dose, with the correction of the lung retention, divided by cardiac output (CO). CO was estimated from the initial transit of IMP in the right heart. Cardiac output index (COI), obtained from the integral of the first transit of IMP in the right heart divided by the injected dose, was calibrated by CO measured by Doppler ultrasonography. Regional cerebral blood flow (rCBF) obtained by this method in normal subjects was acceptable. However, the results may be influenced by the injection technique, and careful attention should be considered for clinical application of this method.

Adult↗

Monitoring urinary levels of monocyte chemotactic and activating factor reflects disease activity of lupus nephritis.

Monocytes/macrophages (M phi) have been implicated in the pathogenesis of lupus nephritis (LN), but the precise molecular mechanism of recruitment and activation of M phi in LN remains unclear. To clarify the involvement of chemotactic cytokines (chemokines) in those events, we measured levels of monocyte chemotactic and activating factor (MCAF, also termed monocyte chemoattractant protein-1, MCP-1) in urines and sera derived from 42 patients with LN. Both urinary and serum MCAF levels were significantly higher in patients with LN as compared with 22 healthy volunteers (10.3 +/- 3.2 vs. 1.0 +/- 0.1 pg/ml . creatinine, 212.2 +/- 75.8 vs. 66.1 +/- 15.5 pg/ml, respectively, P < 0.05, mean +/- SEM). Histological examination of renal lesions from 41 patients classified 19 as active according to the WHO-defined classes IIIb, IVb and IVc, and 22 as inactive by the WHO-defined classes I, II, IIIc, IVd and V. Urinary MCAF levels in the patients with active lesions were significantly higher than those with inactive lesions (20.3 +/- 6.4 vs. 1.7 +/- 0.3 pg/ml . creatinine, P < 0.01). Moreover, elevated urinary MCAF levels were dramatically decreased during steroid therapy-induced convalescence in 29 patients examined serially (13.9 +/- 4.5 vs. 5.3 +/- 1.7 pg/ml . creatinine, P < 0.001), whereas serum MCAF levels did not change significantly. Endothelial cells, renal epithelial cells and infiltrating mononuclear cells in the tubulointerstitial regions were MCAF-positive in immunohistochemical as well as in situ hybridization analysis. These observations suggest that MCAF is probably involved in the pathogenesis of LN with active lesions, possibly through the recruitment and activation of M phi, and that measurement of urinary MCAF levels may be a useful clinical tool for monitoring the disease activity of LN.

Adolescent↗

Steroid pulse therapy in lupus cystitis.

A middle-aged woman with lupus cystitis showed no other symptoms of lupus vasculitis. Cystoscopic findings revealed mucosal hemorrhage and hyperemia. Histological studies of the bladder showed mucosal edema, inflammatory cellular infiltration and the deposition of immune complexes along the vessels. She was treated with a combination of intravenous methylprednisolone pulse therapy and oral prednisolone. Cystoscopy and histological findings showed appreciable improvement. Elevated urinary levels of chemokines such as interleukin-8 (IL-8) and monocyte chemotactic and activating factor (MCAF) decreased during convalescence. These results suggest that the early diagnosis and treatment with steroid pulse therapy achieves improvement of an unusual vasculitis symptom, lupus cystitis.

Anti-Inflammatory Agents↗

Intervention of crescentic glomerulonephritis by antibodies to monocyte chemotactic and activating factor (MCAF/MCP-1).

We investigated the pathophysiological role of a potent macrophage (M(phi)) chemotactic cytokine (chemokine), monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 (MCAF/MCP-1), in an animal model of crescentic glomerulonephritis. Administration of a small dose of nephrotoxic sera induced severe proliferative and necrotizing glomerulonephritis, with crescentic formation in the early phase and glomerulosclerosis in the later phase, in Wistar-Kyoto rats. MCAF/MCP-1 protein was detected immunohistochemically in glomeruli, vascular endothelial cells, and tubular epithelial cells in the early phase of injured kidney tissues but not in normal ones. Anti-MCAF/MCP-1 antibodies decreased the number of M(phi) in glomeruli, and prevented crescentic formation and the fusion of epithelial cell foot process in nephritic rats, thereby decreasing the excreted amounts of protein to normal levels on days 3 and 6. Furthermore, anti-MCAF/MCP-1 antibodies remarkably reduced glomerulosclerosis and improved renal dysfunction as well as proteinuria in the later phase (56 days). These results indicate that MCAF/MCP-1 essentially participates in the impairment of renal functions associated with crescentic glomerulonephritis by recruiting and activating M(phi).

Animals↗

Metabolism of a new local anesthetic, ropivacaine, by human hepatic cytochrome P450.

BACKGROUND: Ropivacaine is a local anesthetic with a long duration of action. Although it is less toxic than bupivacaine, local anesthetic toxicity is possible when the plasma concentration is increased. Because ropivacaine is an amide-type local anesthetic, it is metabolized by cytochrome P450 (P450) in the liver, and its elimination and plasma concentration can be dependent on the level of P450. The purpose of this investigation was to elucidate the metabolism of ropivacaine by human hepatic P450. METHODS: The metabolism of ropivacaine was compared using recombinant human and purified rat hepatic P450 isozymes. An inhibition study using antibodies against rat P450 was performed using hepatic microsomes from human and rat to identify which P450s are involved in ropivacaine metabolism. RESULTS: Ropivacaine was metabolized to 2',6'-pipecoloxylidide (PPX), 3'-hydroxyropivacaine (3'-OH Rop), and 4'-hydroxyropivacaine (4'-OH Rop) by hepatic microsomes from human and rat. PPX was a major metabolite of both human and rat hepatic microsomes. In a reconstituted system with rat P450. PPX was produced by CYP2C11 and 3A2, 4'-OH Rop by CYP1A2, and 3'-OH Rop by CYP1A2 and 2D1. Formation of PPX in rat hepatic microsomes was inhibited by anti CYP3A2, but not by CYP2C11 antibody, and formation of 3'-OH Rop was inhibited by CYP1A2 and 2D1 antibodies. Anti CYP3A2 and 1A2 antibodies inhibited the formation of PPX and 3'-OH Rop in human hepatic microsomes, respectively. Recombinant human P450s expressed in lymphoblast cells were used for further study. CYP3A4 and 1A2 formed the most PPX and 3'-OH Rop, respectively. Ropivacaine N-dealkylation and 3'-hydroxylation activities correlated well with the level of CYP3A4 and 1A2 in human hepatic microsomes, respectively. CONCLUSIONS: Ropivacaine was metabolized to PPX, 3'-OH Rop, and 4'-OH Rop by hepatic P450. PPX was a major metabolite in human hepatic microsomes. CYP3A4 was involved in producing PPX. CYP1A2 was involved in the formation of 3'-OH Rop in human hepatic microsomes.

Amides↗

Synthesis of novel oligosaccharides from leucrose by an alpha-glucosidase.

An alpha-glucosidase was purified in an electrophoretically pure state from an extract of koji culture of Aspergillus sp. KT-11. This enzyme was found to have a transferring activity when the reaction was done in a high concentration of leucrose at pH 4.5. Two kinds of transfer products, fractions I and II, were obtained from leucrose by the enzyme and they were identified as [(alpha-D-glucopyranosyl-(1-->6)-alpha-D-glucopyranosyl-(1-->6)-alpha-D- glucopyranosyl-(1-->5)-D-fructopyranose] and [alpha-D-glucopyranosyl-(1-->6)-alpha-D-glucopyranosyl-(1-->5)-D- fructopyranose], respectively. These are considered to be novel oligosaccharides.

Aspergillus↗

[Value of stress-rest ECG gated SPECT one day protocol using 99mTc-MIBI].

A total of 110 patients suspected with CAD who had symptoms or ECG abnormalities were enrolled in the stress-rest ECG gated SPECT one day protocol using 99mTc-MIBI. All the patients underwent symptom-limited exercise testing and 250 MBq of MIBI was injected at peak exercise. Exercise perfusion SPECT images were reviewed by two trained doctors to classify into three groups; normal, equivocal and abnormal. Patients with normal stress image (n = 53) did not receive the resting study. On the other hand, those with equivocal (n = 20) and abnormal (n = 37) stress images performed resting study, including gated SPECT. Of 20 equivocal cases, 16 patients showed unchanged resting perfusion. All of these had normal wall motion. The remaining 4 patients showed improved resting perfusion, indicating presence of myocardial ischemia. Of 37 abnormal cases, 12 patients showed improved resting perfusion, whereas 25 patients showed unchanged resting perfusion. Cardiac events were more often observed in abnormal cases, especially those associated with myocardial ischemia, while good prognosis was obtained in normal cases. Values of this protocol are (1) Patients with normal stress images need no resting study. (2) All the procedure can be completed in one day. (3) Both cardiac function and perfusion can be obtained with gated SPECT. These data indicates that this protocol is valuable for screening patients suspected with CAD.

Coronary Circulation↗

Effect of amplitude normalization on surface EMG linear envelopes of masticatory muscles during gum chewing.

Various amplitude normalization procedures for surface electromyographic (EMG) signals have been utilized to reduce the inter- and intrasubject variability of data collected on gait analysis. We examined two normalization methods (normalization to mean of ensemble average: NME, and normalization to peak of ensemble average: NPE) for intersubject variability and reproducibility surface EMG profiles for the masticatory muscles during unilateral gum chewing. The EMG profiles for the anterior temporal (Ta), posterior temporal (Tp), masseter (M) and anterior belly of the digastric (Da) muscles on the chewing side from five normal subjects were made at three different sessions. Coefficients of variation and intraclass correlation coefficients were used to assess variability and reproducibility. Each normalization procedure the intersubject variability of unnormalized EMG profiles for Ta, Tp and M. The NME procedure provided lower intersubject variability for Da. The reproducibility of unnormalized profiles for Ta, Tp and M was significantly improved by both procedures (p < 0.05). NME on Da was more effective in its reproducibility (p < 0.05). We found that the phasic characteristics of muscular activity influenced the outcome of amplitude normalization.

Adult↗

Chemical structures of hetero-oligosaccharides produced by Arthrobacter sp. K-1 beta-fructofuranosidase.

The structures of hetero-oligosaccharides obtained by the action of transglycosylation of Arthrobacter sp. K-1 beta-fructofuranosidase, using sucrose as the fructosyl donor, and several mono- and di-sacchrides as the acceptors were investigated. The main transfer products to most reducing mono- and di-sacchrides were non-reducing oligosaccharides with a fructosyl residue linked to a hemiacetal hydroxyl group. In the presence of L-sorbose, the enzyme produced 2-O-beta-D-fructofuranosyl-alpha-L-sorbopyranoside as the major product. With D-galactose or L-arabinose, the enzyme produced not only non-reducing oligosaccharides, but also reducing oligosaccharides, which were identified as 3-O-beta-D-fructofuranosyl-D-galactopyranose and 4-O-beta-D-fructofuranosyl-L-arabinopyranose, respectively. When a non-reducing sugar such as methyl alpha-glucoside was used as an acceptor, the product formed had a fructosyl residue linked at the C6 hydroxyl group.

Arthrobacter↗

Soluble human high-affinity receptor for IgE abrogates the IgE-mediated allergic reaction.

The high-affinity receptor for IgE (Fc epsilon RI) has a tetrameric structure structure composed of one alpha, one beta, and two disulfide-linked gamma subunits, of which the alpha subunit binds IgE with high affinity. A recombinant soluble form of the ectodomain of the human Fc epsilon RI alpha subunit (rsFc epsilon RI alpha) was recently generated by gene engineering and was verified to bind IgE with an affinity as high as that of native Fc epsilon RI on the cell surface. rsFc epsilon RI alpha was prepared on a large scale in order to analyze its biological function. rsFc epsilon RI alpha completely inhibited IgE binding to the cell surface, resulting in abrogation of the chemical mediator release from RBL-2H3 cells. Furthermore it completely abolished the passive cutaneous anaphylaxis (PCA) response by trapping IgE specifically when it was administered into rats prior to IgE sensitization. Even after IgE sensitization, treatment of rsFc epsilon RI alpha substantially reduced the PCA response. It was finally shown that rsFc epsilon RI alpha inhibited IgE binding to human peripheral blood basophils and the histamine release from them. In this paper we address the ability of rsFc epsilon RI alpha to specifically prevent the IgE-mediated allergic reaction.

Animals↗

Evidence for the existence of isozymes of glucose isomerase from Streptomyces phaeochromogenes.

Glucose isomerase from Streptomyces phaeochromogenes was purified from a commercial preparation, Swetase, by DEAE-cellulose, Bio-Gel A-0.5 m, and hydroxyapatite column chromatographies. It was found to be 2 fractions; F-A, not adsorbed on hydroxyapatite and F-B, adsorbed on hydroxyapatite. They were homogeneous in ordinary and SDS-PAGE and had similarities in some enzymatic and physico-chemical properties. The differences, however, were found in the N-terminal amino acid, which was only serine for F-A while it was serine and alanine for F-B, and also in their peptide mapping patterns of digests with trypsin, Achromobacter protease I, and cyanogen bromide. The results suggest that glucose isomerase from S. phaeochromogenes was composed of the two kinds of isozymes and that each of isozymes was a tetramer constituted of non-identical subunits.

Aldose-Ketose Isomerases↗

Internalization of IgE receptors on rat basophilic leukemic cells by phorbol ester. Comparison with endocytosis induced by receptor aggregation.

Phorbol myristate acetate (PMA) can induce a rapid and significant decrease in the expression of IgE receptors on RBL-2H3 cells. Fluorescence microscopy confirmed that the down-regulation is due to internalization of receptors. The endocytotic response to PMA shares several characteristics with endocytosis induced by immunochemical aggregation of surface-bound monomeric IgE: the rates of internalization both have a t1/2 of about 5 min, a maximum of 35% of the surface-bound IgE can be endocytosed by the action of PMA (50% by receptor aggregation), endocytosis is sustained for at least up to 60 min, neither stimulus requires extracellular Ca2+ and endocytosis induced by either stimulus is an active process, i.e., is dependent on temperature and cellular energy. Biochemical studies revealed some differences between the endocytotic responses to the two stimuli. After prolonged treatment of cells with dexamethasone, only endocytosis induced by PMA is inhibited. Cells depleted of protein kinase C by prolonged exposure to PMA can sustain a significant endocytotic response to aggregation of IgE receptors, but become completely desensitized to PMA. These data suggest that different biochemical pathways mediate the signals from the two stimuli and that protein kinase C is directly involved in endocytosis induced by PMA but does not have a major role in endocytosis induced by receptor aggregation.

Animals↗

Molecular cloning and characterization of MACIF, an inhibitor of membrane channel formation of complement.

Human erythrocytes contain a membrane protein, MACIF, which inhibits the formation of a membrane attack complex (MAC) of complement. We have cloned and sequenced the complementary DNA of MACIF messenger RNA. The amino acid sequence predicted from its nucleotide sequence consists of 128 amino acids. The amino-terminal 25 residues may correspond to a signal peptide. The carboxy-terminal sequence confirmed that MACIF is a glycosylphosphatidylinositol (GPI)-anchored protein. The amino acid sequence of MACIF was partially determined by established techniques for protein chemistry and the resultant sequence was consistent with that predicted from the nucleotide sequence. The results of sequence analyses also suggested that asparagine at the 18th position was N-glycosylated. When mRNA obtained from the MACIF cDNA clone with SP6 RNA polymerase was microinjected into Xenopus oocytes, the oocytes synthesized a product which exhibited MACIF activity and reacted with anti-MACIF antibody. Comparison of the predicted sequence revealed significant homology with mouse Ly-6 antigens.

Amino Acid Sequence↗

Recycling of receptor-bound IgE by rat basophilic leukemia cells.

Rat basophilic leukemia (RBL) cells have receptors for immunoglobulin E (IgE). We previously showed that unlike some other ligands, the binding of monomeric rat or mouse IgE to RBL cells does not induce endocytosis. However, aggregation of the cell-bound, monomeric mouse IgE anti-dinitrophenyl (DNP) with DNP-protein conjugates leads to endocytosis of the aggregated mouse IgE and to the co-endocytosis of some unaggregated monomeric rat IgE. In this study we analyzed and compared the fate of co-endocytosed and endocytosed IgE. We found that co-endocytosed rat IgE recycled back to the cell surface within 3 to 4 hr. In contrast, endocytosed, immunochemically cross-linked, receptor-bound mouse IgE anti-DNP was partially degraded and was released into the medium, with no observable recycling of receptors, by 3 hr. However, addition of the hapten, DNP-lysine, resulted in rapid recycling (t1/2 10 min) of the endocytosed receptor-bound IgE to the plasma membrane and blocked additional endocytosis. Recycling of the endocytosed mouse IgE was more pronounced when the hapten was added to cells within 20 min of the initiation of endocytosis. When the hapten was added to the cells at later times (60 to 180 min), progressively less IgE recycled to the surface. This may reflect shuttling of the internalized IgE from a 'prelysosomal' to a 'lysosomal' compartment. Thus we provide evidence for recycling of monomeric IgE receptor complexes, sorting between cross-linked and non-cross-linked IgE receptor complexes, the freeing of receptor-bound monomeric IgE from the endocytosed immune-complexed IgE, and the apparent dependence of the recycling efficiency upon intracellular localization.

Animals↗

Endocytosis of aggregated immunoglobulin G by rat basophilic leukemia cells; rate, extent, and effects on the endocytosis of immunoglobulin E.

Rat basophilic leukemia (RBL) cells have distinct receptors for IgE and IgG. We assessed the endocytosis of chemically and immunochemically cross-linked mouse-IgG and its influence on the simultaneous endocytosis of IgE. We found that at 37 degrees C, aggregates of IgG and IgE were endocytosed at about the same rate with one-half of the maximal endocytosis occurring in 5 to 13 min, and the efficiency of endocytosis for both ligands ranging from 40 to 70%. We also found that endocytosis of cross-linked IgE and IgG occurred simultaneously and neither ligand significantly affected the rate or extent of endocytosis of the other. The cells accumulated the cross-linked IgG, and then released it to the extracellular environment, at a rate (less than 3%/hr) slower than the released endocytosed IgE (greater than 10%/hr). Using an assay that discriminates between unbound and receptor-bound oligomeric IgG, we found that oligomeric IgG is endocytosed with its receptor, and that the bulk of the ligand remains bound to its receptor for greater than 120 min after endocytosis. The differences in the rate of release of endocytosed IgG vs IgE suggests that the intracellular fate or pathway of these two oligomeric ligands may differ.

Animals↗