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Biomedical subjects

K Furuichi

Publications and source records attributed to K Furuichi.

At least 37 records · Page 2Linked to original sources
PubMed2000

[A case of high-age minimal change nephrotic syndrome relapse after 18-year remission and effective treatment with steroid and cyclosporin combined therapy].

We describe the clinical course of a 69-year-old woman, who suffered from minimal change nephrotic syndrome(MCNS) after long-term remission. In 1979, she was admitted to Kanazawa University Hospital due to MCNS verified by renal biopsy and was treated with oral prednisolone(initially 40 mg/day) for two years. She suffered from edema again in 1999 with massive proteinuria. Renal biopsy revealed minor glomerular abnormality without any deposition of immunoglobulins or complements. Electron microscopic findings showed extensive foot process effacement. Therefore, we diagnosed this case as a recurrence of MCNS. She was treated with the combination of methylprednisolone pulse therapy(500 mg, 3 days), oral prednisolone(20 mg/day) and cyclosporin(CyA, 3 mg/kg/day), which could induce earlier complete remission. These results suggest that recurrence after long-term remission could occur in adult-onset MCNS and that the combination therapy of prednisolone and CyA may be effective for the induction of early remission in MCNS.

Administration, Oral↗
PubMed1999

Identification of a novel 300-kDa factor termed IkappaB alphaE3-F1 that is required for ubiquitinylation of IkappaB alpha.

Destruction of IkappaB by ubiquitinylation is required for signal-dependent activation of NF-kappaB. The IkappaB alpha ubiquitin-ligase activity associated with phosphorylated IkappaB alpha (pIkappaB alpha) in HeLa cells was almost completely lost by washing under stringent conditions including 1 M NaCl; nevertheless, an SCF(betaTrCP) complex containing Skp1, Cullin-1, and F-box/WD40 protein betaTrCP was still bound to pIkappaB alpha, suggesting the existence of a putative factor that is loosely associated with pIkappaB alpha and may collaborate with SCF(betaTrCP). The factor was named IkappaB alphaE3-F1 and was partially purified from HeLa cells. Gel filtration analysis revealed that IkappaB alphaE3-F1 has an apparent molecular mass of approximately 300 kDa.

Blotting, Western↗
PubMed1999

New ether-à-go-go K(+) channel family members localized in human telencephalon.

A cDNA encoding a novel voltage-gated K(+) channel protein was isolated from human brain. This protein, termed BEC1, is 46% identical to rat elk in the ether-à-go-go K(+) channel family. The BEC1 gene maps to the 12q13 region of the human genome. Northern blot analysis indicates that BEC1 is exclusively expressed in human brain, where the expression is concentrated in the telencephalic areas such as the cerebral cortex, amygdala, hippocampus, and striatum. By in situ hybridization, BEC1 is detected in the CA1-CA3 pyramidal cell layers and the dentate gyrus granule cell layers of the hippocampus. Specific signals are also found in neocortical neurons. Transfection of mammalian L929 and Chinese hamster ovary cells with BEC1 cDNA induces a voltage-gated outward current with a fast inactivation component. This current is insensitive to tetraethylammonium and quinidine. Additionally, a second related gene BEC2 was isolated from human brain. BEC2 is also brain-specific, located in the neocortex and the striatum, and functional as a channel gene. Phylogenetic analysis indicates that BEC1 and BEC2 constitute a subfamily, together with elk, in the ether-à-go-go family. The two genes may be involved in cellular excitability of restricted neurons in the human central nervous system.

Amino Acid Sequence↗
PubMed1999

Identification of a domain affecting agonist potency of meta-chlorophenylbiguanide in 5-HT3 receptors.

The pharmacological properties of rat and human 5-HT3 receptors expressed in Xenopus oocytes were assessed using a two-electrode voltage clamp technique. Meta-chlorophenylbiguanide (mCPBG), a 5-HT3 receptor-selective agonist, elicited typical current responses in both rat and human 5-HT3 receptor-expressing oocytes. However, the EC50 value for rat 5-HT3 receptors was 13-fold lower than for human 5-HT3 receptors. Using several chimeric human-rat 5-HT3 receptors, we identified a potential domain responsible for this difference in mCPBG-response. The domain is in the N-terminal extracellular region adjacent to the first transmembrane domain of rat 5-HT3 receptors and includes a rat-specific seven amino acid sequence (Phe197, Thr198, Lys199, Gln201, Ile205, Thr207 and Ser210). Replacement of corresponding amino acids in human 5-HT3 receptors by rat receptor residues increased the potency of mCPBG on human receptors indicating these amino acids play an important role in the pharmacological response to mCPBG.

Amino Acid Sequence↗
PubMed1999

IkappaBalpha ubiquitination is catalyzed by an SCF-like complex containing Skp1, cullin-1, and two F-box/WD40-repeat proteins, betaTrCP1 and betaTrCP2.

Destruction of the transcriptional inhibitor IkappaB by the ubiquitin (Ub) system is required for signal-dependent activation of the multifunctional transcriptional factor NF-kappaB, but details of this ubiquitination are largely unknown. We report here that the IkappaBalpha-ubiquitin ligase (IkappaBalpha-E3) is an SCF-like complex containing Skp1, cullin-1, and two homologous F-box/WD40-repeat proteins, betaTrCP1 and betaTrCP2. Intriguingly, all these components are cooperatively recruited to bind to a phosphorylated IkappaBalpha (pIkappaBalpha) produced by tumor necrosis factor-alpha (TNF-alpha) stimulation. IkappaBalpha-E3 bound to pIkappaBalpha catalyzed in vitro ubiquitination of pIkappaBalpha in the presence of ATP, Ub, and E1-activating and E2-conjugating enzymes. Forced expression of betaTrCP1 and betaTrCP2 resulted in dramatic augmentation of the in vitro polyubiquitination activity of IkappaBalpha-E3. These results indicate that the long-sought IkappaBalpha-E3 is an SCF-like complex consisting of multiple proteins which are coordinately assembled during phosphorylation of IkappaBalpha in response to external signals.

Amino Acid Sequence↗
PubMed1999

In vivo and in vitro recruitment of an IkappaBalpha-ubiquitin ligase to IkappaBalpha phosphorylated by IKK, leading to ubiquitination.

Activation of the transcriptional factor NF-kappaB is triggered by signal-dependent degradation of its inhibitor protein IkappaB through the ubiquitin (Ub)-proteasome pathway. We found here that a phosphorylated IkappaBalpha immunoprecipitated (IP-pIkappaBalpha) from the crude extract of HeLa cells which had been treated with tumor necrosis factor-alpha (TNFalpha) caused a dramatic ubiquitination of itself, termed autoubiquitination, when incubated with ATP, Ub, and E1-activating and E2-conjugating enzymes. IP-pIkappaBalpha also catalyzed ubiquitination of an in vitro synthesized 35S-IkappaBalpha previously phosphorylated by IkappaB-kinase (IKK) which is referred to as transubiquitination. No appreciable activity of auto- and transubiquitination was observed in an unphosphorylated IP-IkappaBalpha. Moreover, the putative IkappaBalpha-Ub ligase (IkappaBalpha-E3) present in HeLa cell cytosol associated in vitro with an IKK-phosphorylated recombinant IkappaBalpha, a process independent of NF-kappaB binding to IkappaBalpha or TNFalpha stimulation. Replacement of the two Ser residues at positions 32 and 36 corresponding to IKK phosphorylation sites by Ala resulted in almost complete prevention of binding of an IkappaBalpha-E3 to IkappaBalpha. These results indicate that phosphorylation of IkappaBalpha is necessary and sufficient for recruitment of this IkappaBalpha-E3 to associate with IkappaBalpha.

Adenosine Triphosphate↗
PubMed1999

Ion permeation properties of a cloned human 5-HT3 receptor transiently expressed in HEK 293 cells.

Human 5-HT3 receptors expressed in HEK 293 cells were studied using patch-clamp techniques. The permeability ratios of cations to Na+ were Li+, 1.16; K+, 1.04; Rb+, 1.11; Cs+, 1.11; NMDG+, 0.04; Ca2+, 0.49, and Mg2+, 0.37. The permeability sequence of the alkali metal cations was Li+ > Rb+ = Cs+ > K+ > Na+. Increased external concentrations of Ca2+ or Mg2- decreased 5-HT-induced currents at all potentials tested in a voltage-independent manner. The single-channel conductance of human 5-HT3 receptors measured by fluctuation analysis of whole-cell currents was 790 +/- 100 fS. Differences in the basic properties of 5-HT3 receptors between species may explain interspecies differences in pharmacological properties.

Cations↗
PubMed1999

Exacerbation of glomerulonephritis in subjects with chronic hepatitis C virus infection after interferon therapy.

We previously reported the glomerular deposition of hepatitis C virus (HCV) core antigen (Ag) in HCV-related nephropathy. In this study, we analyzed 23 HCV-positive subjects with exacerbation of proteinuria and/or hematuria during interferon (IFN) therapy and measured urinary protein selectivity. We also examined the involvement of HCV-related Ag using anti-HCV core (capside) Ag murine monoclonal antibody (Ab) and anti-core2 rabbit polyclonal Abs in nine subjects. Of 17 subjects, 13 (78%) showed low selective proteinuria. We found mesangial proliferative glomerulonephritis in 9 subjects, membranoproliferative glomerulonephritis in 1 subject, and nephrosclerosis in 1 subject. Immunofluorescence study showed the glomerular deposition of immunoglobulin G (IgG) or IgA and complements in all 9 subjects examined. Trace amounts only of HCV core Ag were detected along the glomerular capillary wall in 3 of 9 subjects (33%). Electron microscopy showed subendothelial or mesangial electron-dense deposits and also foot process effacement (20% to 72.5% of glomerular capillary walls) in all subjects and endothelial swelling in 4 subjects. In conclusion, IFN therapy for HCV may exacerbate the underlying glomerulopathies, unrelated to HCV Ags, through direct or indirect effects on glomerular endothelial and epithelial cells. Physicians should carefully distinguish HCV-related nephropathy from other glomerular diseases when they administer IFN therapy to HCV-positive subjects.

Adult↗
PubMed1999

Induction of general anesthesia using propofol for cesarean section of a woman with cerebral palsy.

A 45-year-old pregnant woman with cerebral palsy was scheduled for cesarean section at 37 weeks' gestation due to the risk of athetotic reaction. Spinal anesthesia appeared difficult to perform due to maintenance position, and because maternal respiratory depression due to athetotic reaction to mechanical stimulation might cause fetal hypoxia. We therefore selected general anesthesia. Propofol and succinylcholine were intravenously (i.v.) administered for induction, and additional propofol was administered i.v. for hemodynamics stabilization. Neonatal Apgar scores were 8 at one minute and 10 at five minutes. No maternal respiratory depression was observed postoperatively, and a healthy baby was successfully delivered.

Anesthesia, General↗
PubMed1999

MIP-1alpha and MCP-1 contribute to crescents and interstitial lesions in human crescentic glomerulonephritis.

BACKGROUND: The precise molecular mechanisms of macrophage (Mphi) recruitment and activation in crescentic glomerulonephritis remain to be investigated. We hypothesized that locally produced macrophage inflammatory protein (MIP)-1alpha and monocyte chemoattractant protein (MCP)-1 via the chemokine receptors participate in the pathophysiology of human crescentic glomerulonephritis by recruiting and activating Mphi. METHODS: We investigated the levels of MIP-1alpha and MCP-1 by enzyme-linked immunosorbent assay (ELISA) in 20 healthy subjects, 20 patients with crescentic glomerulonephritis, and 41 control patients with various other renal diseases. The presence of MIP-1alpha, MCP-1, and the cognate chemokine receptor for MIP-1alpha, CCR5, in the diseased kidneys was evaluated by immunohistochemical and in situ hybridization analyses. RESULTS: MIP-1alpha-positive cells were mainly detected in crescentic lesions, whereas MCP-1 was mainly in the interstitium. In addition, we detected CCR5-positive cells in diseased glomeruli and interstitium. Urinary MIP-1alpha was detected in crescentic glomerulonephritis, even though it was below detectable levels in healthy subjects and in patients with other renal diseases without crescents. Urinary MIP-1alpha levels in the patients with crescentic glomerulonephritis were well correlated with the percentage of cellular crescents and the number of CD68-positive infiltrating cells and CCR5-positive cells in the glomeruli. However, urinary MCP-1 levels were well correlated with the percentage of both total crescents and fibrocellular/fibrous crescents and the number of CD68-positive infiltrating cells in the interstitium. Moreover, elevated urinary levels of both MIP-1alpha and MCP-1 dramatically decreased during glucocorticoid therapy-induced convalescence. CONCLUSIONS: These observations suggest that locally produced MIP-1alpha may be involved in the development of cellular crescents in the acute phase via CCR5 and that MCP-1 may be involved mainly in the development of interstitial lesions in the chronic phase when fibrocellular/fibrous crescents are present, possibly through Mphi recruitment and activation.

Adolescent↗
PubMed1999

Eotaxin contributes to renal interstitial eosinophilia.

BACKGROUND: A potent eosinophil chemotactic cytokine, human eotaxin, is directly chemotactic for eosinophils. Therefore, the specific expression of eotaxin in tissue might play a crucial role in tissue eosinophilia. However, the precise molecular mechanism of the recruitment and activation of eosinophils in human renal diseases remains to be investigated. We evaluated the role of eotaxin in the pathogenesis of human diffuse interstitial nephritis with marked infiltration of eosinophils. METHODS: In this study, we examined 20 healthy volunteers. 56 patients with primary or secondary glomerular diseases and two hypereosinophilic syndrome patients without renal involvement. Urinary and serum eotaxin levels were determined by an enzyme-linked immunosorbent assay. We also detected the presence of eotaxin protein immunohistochemically. RESULTS: On the one hand, urinary levels of eotaxin were significantly higher before the initiation of glucocorticoid administration in the patient with interstitial nephritis with marked infiltration of eosinophils. On the other hand, urinary eotaxin levels were not detected in any patients with nephrotic syndrome, interstitial nephritis without eosinophils, hypereosinophilic syndrome without renal involvement or other renal diseases. Serum eotaxin levels were not detected in any of the patients. Therefore, the detection of eotaxin in the urine was specific for renal interstitial eosinophilia. Moreover, endothelial cells, infiltrating mononuclear cells and renal epithelial cells in the tubulointerstitial lesions were immunostained with specific anti-eotaxin antibodies. Furthermore, the elevated urinary levels of eotaxin decreased dramatically during glucocorticoid-induced convalescence. HYPOTHESIS: We hypothesize that in situ expression of eotaxin may provide a new mechanism to explain the renal interstitial eosinophil infiltration.

Adolescent↗
PubMed1999

The short- and long-term outcomes of membranous nephropathy treated with intravenous immune globulin therapy. Kanazawa Study Group for Renal Diseases and Hypertension.

BACKGROUND: A considerable diversity in prognosis is seen with membranous nephropathy (MN). A recent report showed beneficial effects of immune globulin (Glb) therapy in Heymann nephritis, a rat model of MN. However, the early and late clinical effects of Glb in human MN have remained unclear. METHODS: We studied retrospectively 86 patients with primary MN from 1965 to 1988 who were followed for at least 5 years, or until renal or actual death. Thirty patients were non-randomly treated with 1-3 courses of intravenous immune globulin, 5-10 g/day (100-150 mg/kg/day) for 6 consecutive days. Based on electron microscopic (EM) findings, the patients were divided into two subtypes, i.e. homogeneous type with synchronous electron-dense deposits, and heterogeneous type with various stages of dense deposits, due to their different clinical outcomes. RESULTS: There was no difference in the initial clinicopathological states between Glb (n = 30) and non-Glb group (n = 56) (70 vs. 68% in nephrotic state; 37 vs. 39% in female, 50 vs. 52% in homogeneous type, 50 vs. 48% in heterogeneous type respectively). For the homogeneous type, at 6 months post-treatment, Glb therapy had induced earlier remission as compared to non-Glb treatments with corticosteroid alone or together with cyclophosphamide (57 vs. 10% respectively, P = 0.006). However, there was no significant difference in the early therapeutic effect for the heterogeneous type (13% for Glb vs. 5% for non-Glb in remission after 6 months), or in the final outcome for all groups (18% for Glb vs. 10% for non-Glb in renal death after 15 years). No adverse effects were recorded during or after Glb therapy. CONCLUSIONS: Our results suggest that short-term relatively low-dose intravenous Glb therapy has a beneficial effect in the earlier induction of remission in a subgroup of MN, the homogeneous type with EM findings of synchronous electron-dense deposits, but does not alter the long-term outcome of human MN.

Adolescent↗
PubMed1999

Coronary artery spasm induced by trigeminal nerve stimulation and vagal reflex during intracranial operation.

This report describes a case of ventricular fibrillation resulting from coronary vasospasm during intracranial operation under general anesthesia. An autonomic response associated with the intracranial procedure caused a coronary spasm, which was worsened by alpha-agonists. Nitroglycerin effectively resolved the coronary spasm and co-complications persisted.

Adrenergic alpha-Agonists↗
PubMed1999

[The role of monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein (MCP)-1 in subgroups of rapidly progressive glomerulonephritis].

To elucidate the role of monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein(MCP)-1 in the pathogenesis of rapidly progressive glomerulonephritis (RPGN), we determined the urinary levels of MCAF/MCP-1 in 20 healthy subjects, 30 patients showing RPGN with crescents, and 39 patients with various types of renal diseases without crescents. We divided RPGN into two subgroups, the acute type and the insidious type, with regard to the declination rate of reciprocals of serum creatinine with time as previously reported. In addition, we divided the patients with RPGN into anti-neutrophil cytoplasmic antibody(ANCA)-related diseases and immune complex(IC)-mediated diseases with regard to etiology. Urinary levels of MCAF/MCP-1 were significantly higher in patients with RPGN as compared with those of other renal diseases and healthy volunteers(21.8 +/- 4.5 vs. 11.6 +/- 3.5, 1.0 +/- 0.1 pg/ml creatinine, respectively, p < 0.01, mean +/- SEM). There was no difference in the urinary levels of MCAF/MCP-1 between the acute and insidious types of RPGN patients. In addition, there was no difference in the urinary levels of MCAF/MCP-1 between the patients with ANCA-related and IC-mediated diseases. Urinary levels of MCAF/MCP-1 in patients with RPGN were correlated well with the percentage of both total crescents and fibrocellular/fibrous crescents and the number of CD68-positive infiltrating cells in the interstitium. Immunohistochemical examinations revealed that MCAF/MCP-1 positive cells were detected in tubular epithelial and endothelial cells and mononuclear infiltrated cells in the interstitium. Moreover, elevated urinary MCAF/MCP-1 levels in patients with RPGN, regardless of subgroups, were dramatically decreased during methylprednisolone pulse therapy induced convalescence. These results suggest that MCAF/MCP-1 may be involved in the pathogenesis of RPGN via macrophage recruitment and activation.

Anti-Inflammatory Agents↗
PubMed1998

Urinary levels of chemokines (MCAF/MCP-1, IL-8) reflect distinct disease activities and phases of human IgA nephropathy.

Leukocytes have been implicated to be involved in the pathogenesis of IgA nephropathy (IgAN). To clarify the precise molecular mechanism of recruitment and activation of leukocytes in the subgroups of IgAN, latent, acute, and chronic types, we studied monocyte chemotactic and activating factor (MCAF/MCP-1) and interleukin (IL)-8 in urines and renal expression of these cytokines. Urinary MCAF levels were significantly higher in chronic type, and were correlated with pathological progressive factors such as mesangial proliferation and interstitial cellular infiltration associated with CD68-positive macrophage. On the other hand, urinary IL-8 elevated only in acute type and were correlated with glomerular endocapillary proliferation and the degree of hematuria. In immunohistochemical study, IL-8 was mainly observed in glomeruli, otherwise MCAF in vascular endothelial cells, tubular epithelial cells, and infiltrated mononuclear cells in the interstitial lesions. These observations demonstrated that MCAF and IL-8 were differentially expressed in kidneys with IgAN, and their subtypes, and suggest that chemokines may be involved in the pathogenesis of IgAN at distinct phases or pathological lesions, possibly through the recruitment and activation of a distinct type of leukocyte.

Adolescent↗