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Biomedical subjects

K Ichikawa

Publications and source records attributed to K Ichikawa.

At least 163 records · Page 9Linked to original sources
PubMed1998

[A case of polyneuropathy associated with osteosclerotic myeloma].

A 50-year-old woman presented with sensorimotor polyneuropathy in the lower limbs. Biopsy of the muscle revealed neurogenic changes, and electrophysiological study and pathology of the biopsied nerve indicated myelinoaxonal degeneration. Her symptoms responded to neither plasmapheresis nor prednisolone. Pelvic radiography disclosed an osteosclerotic lesion that was subsequently diagnosed as IgA-lambda plasmacytoma by biopsy. Radiation therapy for this solitary osteosclerotic myeloma improved the patient's polyneuropathy. In Japan, reports of cases of polyneuropathy associated with osteosclerotic myeloma without multiorgan disorders as in our case have not previously been described; thus, such cases may be misdiagnosed. Therefore, in patients with polyneuropathy of unknown etiology, a systemic bone survey and repeated searches for M-protein are important. Treatment of bone lesions in patients with solitary osteosclerotic myeloma may improve the associated polyneuropathy.

Female↗
PubMed1998

[Quantitative levels of serum amyloid A protein and other proteins in cerebrospinal fluid and serum of patients with meningitis].

Serum amyloid A protein (SAA), a putative precursor of the AA protein which constitutes amyloid fibrils in secondary amyloidosis, is evaluated as a sensitive acute-phase reactant in serum. At present, SAA concentration in serum is determined by latex nephelometry, but this assay cannot detect SAA in the low concentration range lower than 10 ng/ml. We have developed a sensitive enzyme immunoassay (EIA) for determining low concentrations of SAA. The assay is reproducible, reliable and requires no pretreatment of specimen prior to assay. We measured levels of SAA by this EIA in both cerebrospinal fluid (CSF) and serum of patients with suspected meningitis, measured also levels of albumin, alpha 2 macroglobulin and C-reactive protein (CRP) to investigate if these protein levels are useful for differential diagnoses of meningitis and for indicators damage of blood-CSF barrier. The SAA reference value in CSF is 3.99 +/- 1.74 ng/ml (mean +/- SD for nonmeningitis patients). The CRP concentration in CSF in bacterial meningitis was much higher than in viral meningitis, but CRP in CSF was also high in bacterial infection other than meningitis. On the other hand, SAA concentration in CSF in these patients with any meningitis are significantly higher than the reference values of SAA (p < 0.001). However, the differences in SAA concentrations among the three types (bacterial, viral and mycotic meningitis) of meningitis were not significant.

Acute-Phase Proteins↗
PubMed1998

Anti-beta2-glycoprotein I antibodies.

The relationship between presence of anti-beta2-glycoprotein I autoantibodies (abeta2-GPI) and history of thrombosis is now widely known. However, differences in the methodology of abeta2-GPI detection have made the comparison of data from different laboratories extremely difficult. We discuss the significance of abeta2-GPI of the IgG, IgM and IgA isotypes, and our approach to developing an easier and more reproducible method for the detection of this autoantibody. In addition, we present data that shows that commercially available enzyme immunoassay plates differ regarding detectability of abeta2-GPI. Since the clinical significance of this heterogeneity is presently unclear, the set-up of the detection systems and interpretation of data need great care.

Animals↗
PubMed1997

Trans-regulation of myogenin promoter/enhancer activity by c-ski during skeletal-muscle differentiation: the C-terminus of the c-Ski protein is essential for transcriptional regulatory activity in myotubes.

c-ski gene product is a nuclear protein with myogenesis-promoting and transforming activities. We have analysed the effects of c-ski transfection on the promoter/enhancer activity of the upstream region of the myogenin gene during in vitro myogenesis using CAT reporter assay. When co-transfected with c-ski into myogenic C2C12 cells, promoter/enhancer activity was efficiently suppressed in proliferating cells, but the myogenesis-induced increase in activity was potentiated approximately ten times more (150-fold in the ski-transfected cells) than the ordinary increase (12-fold in the mock) 48 h after induction of differentiation. In non-myogenic 10T1/2 cells, c-ski transfection caused persistent suppression of promoter/enhancer activity in both proliferating and growth-arrested (i.e. myogenesis-inducing) conditions. Thus the ski-dependent potentiation of myogenin gene transcriptional activity appears to be specific for myogenesis. The C-terminal region (amino acids 595-663) of the c-Ski protein was essential for the potentiating activity in myotubes. Other members of the ski-gene family, snoN and snoA, were ineffective in transactivation, possibly because of the defect in the corresponding C-terminal region. c-Ski protein underwent a mobility shift on SDS/PAGE after in vitro myogenesis which may explain the conversion of the activity from suppressive in myoblasts to potentiating in myotubes. Deletion analysis of the upstream region of the myogenin gene revealed that a responsive element to c-ski in myotubes is located at a distinct site upstream of the basal promoter/enhancer region.

Animals↗
PubMed1997

Na+-dependent glucose uptake and collagen synthesis by cultured bovine retinal pericytes.

This study was performed to clarify the presence of sodium-dependent glucose uptake and its role in the synthesis of type IV and type VI collagen by cultured bovine retinal pericytes. The glucose uptake by retinal pericytes and retinal endothelial cells was measured using 3H-D-glucose in the presence or absence of sodium. Glucose uptake in the presence of sodium was twice as high as that observed in the presence of phlorizin and sodium or in the absence of sodium. Sodium-dependent glucose uptake was observed at different sodium concentrations, and its half-maximal stimulation occurred at 48 mM. These findings were not observed in retinal endothelial cells. Levels of type IV and type VI collagen produced by retinal pericytes were significantly increased at glucose concentrations higher than 20 mM. Phlorizin decreased both collagen synthesis and glucose consumption by retinal pericytes incubated with 30 mM of glucose to the levels observed with 5 mM of glucose. These data suggest that sodium-dependent glucose uptake is present in retinal pericytes and that excessive glucose entry into the cell is an important factor for overproduction of collagen. Phlorizin normalized the synthesis of type IV and type VI collagen with decreasing glucose consumption under high glucose conditions.

Animals↗
PubMed1997

Expression of somatostatin receptor subtype 2 mRNA in human lymphoid cells.

We analyzed the mRNA expression of somatostatin receptor subtypes 1 to 5 (SSTR1-5) in human lymphoid cell lines, human peripheral blood lymphocytes (PBL), and human lymphatic leukemia cells, using the reverse transcription-polymerase chain reaction method. In human lymphoid cell lines, SSTR2 mRNA expression was clearly detectable, and there was no evidence of SSTR1 mRNA expression. SSTR2 mRNA was barely detectable in PBL from healthy individuals but was clearly detectable in EB virus-transformed lymphocytes. Lymphocytes from some of the leukemic patients showed elevated SSTR2 mRNA expression. SSTR2 mRNA expression in PBL was upregulated upon stimulation by PHA. SSTR3 mRNA was also observed in all the cell lines examined, although in one cell line, the expression was weak. Some cell lines showed little or no SSTR4 or 5 mRNA expression. The expression pattern of SSTR2 mRNA suggests that this receptor may have some important roles in lymphocyte activation, development, and/or tumorgenesis.

Cell Line↗
PubMed1997

Ligand-dependent heterodimerization of thyroid hormone receptor and retinoid X receptor.

The thyroid hormone receptors (TR) bind to cis-acting DNA elements as heterodimers with the retinoid X receptors (RXR). These heterodimers display distinct specificities in mediating the hormonal response to target gene transcription. We characterized the interaction between TRalpha1 and RXRalpha via their ligand binding domains (LBDs) and the effect of ligands on the interaction using a yeast two-hybrid system. The DNA binding domain (BD) of yeast Gal4 fusion to the LBD of TRalpha1 had no transcriptional activity on its own, but when it was coexpressed with the activation domain (AD) of yeast Gal4 fusion to LBD of RXRalpha conferred activation to a reporter gene harboring a Gal4 binding site, indicating that LBDs of TRalpha1 and RXRalpha interact with each other in solution. Furthermore, T3 and 9-cis-RA increased the reporter activity, and an additive effect was observed when both ligands were added, indicating that the TRalpha1.RXRalpha heterodimerization is augmented by their respective ligands in vivo. Using an in vitro pull-down experiment, we confirmed the ligand-dependent interaction observed in the yeast system. Matrix-bound glutathione S-transferase-RXRalpha specifically coprecipitated the 35S-labeled TRalpha1 above the control, and associated 35S-labeled TRalpha1 was increased by the addition of T3 and 9-cis-RA. These results imply a complex, sensitive cross-talk in vivo among nuclear receptors and their respective ligands through distinct hormonal signaling pathways.

Alitretinoin↗
PubMed1997

Evidence for myosin-binding phosphatase in heart myofibrils.

Protein phosphatase was partially purified from myofibrils of bovine heart by sequential column chromatographies. The purified protein phosphatase was immunologically identified as a delta isoform of PP1 (PP1delta). The myosin-binding subunit (MBS) of myosin-binding phosphatase (MBP) in smooth muscle was co-purified with PP1delta at each step of the sequential column chromatographies. The immunoprecipitation experiment using the polyclonal antibody to MBS showed that PP1delta associates with MBS in the purified phosphatase. In addition, the myosin-binding assay showed that the purified phosphatase has the characteristics of binding to cardiac myosin. These data strongly suggest that MBP, the holoenzyme composed of PP1delta and MBS, is expressed in heart myofibrils.

Animals↗
PubMed1997

Interaction of smooth muscle myosin phosphatase with phospholipids.

The 130 kDa myosin-binding subunit (MBS) of smooth muscle myosin phosphatase was detected in cytoskeletal, cytosolic, and membrane fractions of T24 cells. Also, MBS was distributed between cytoplasm and plasmalemma in mitotic REF52 cells. These observations prompted this study of the interaction(s) of phospholipids with myosin phosphatase. Using a sedimentation assay, gizzard myosin phosphatase bound to vesicles of acidic phospholipids, i.e. phosphatidylserine (PS), phosphatidylinositol, and phosphatidic acid (PA). Neutral phospholipids did not bind. Binding of PS to myosin phosphatase also was demonstrated by electrophoresis under nondenaturing conditions. Preferential binding of PA, compared to that of the other acidic phospholipids, was indicated. Interaction of acidic phospholipids with myosin phosphatase inhibited phosphatase activity toward phosphorylated myosin. The extent of PS binding with myosin phosphatase decreased on increasing ionic strength and Mg2+ concentration. MBS (M130/M133) and M20 were phosphorylated by protein kinase A to 3 and 1 mol of P/(mol of subunit), respectively. Phosphorylation of the holoenzyme decreased phospholipid binding with recovery of phosphatase activity. Using limited proteolysis of the holoenzyme and various mutants, it was shown that phospholipid binding was associated with the C-terminal part of MBS, Ser 667-Ile 1004, and M20. The phosphorylation site involved in regulation of phospholipid binding is within the C-terminal MBS sequence. These results suggest that myosin phosphatase may interact with membranes and that phosphorylation by protein kinase A could modify this interaction. This mechanism could be important in localization of myosin phosphatase and in targeting substrates at different loci.

Animals↗
PubMed1997

Sarcomatoid renal cell carcinoma with widespread metastases to liver and bones in a kidney transplant recipient.

A case of sarcomatoid renal cell carcinoma with widespread metastases to liver and bones in a cadaver renal transplant recipient is reported in this article. The patient underwent a kidney transplant at the age of 43 and was treated with various immunosuppressive agents after surgery. Twelve months after the transplantation, multiple tumors were found in the liver, and the patient died 8 months later. Pathological examination at autopsy revealed renal cell carcinoma with a sarcomatoid component in the right native kidney and metastases to liver and bones. It is unusual for renal cell carcinoma to undergo sarcomatous transformation and to metastasize to the liver before reaching other organs. We speculate that immunosuppressants may have altered malignant cell proliferation, invasion, and the form of metastasis in this case.

Adult↗
PubMed1997

Anti-beta2-glycoprotein I (beta2GPI) monoclonal antibodies with lupus anticoagulant-like activity enhance the beta2GPI binding to phospholipids.

beta2-Glycoprotein I (beta2GPI), a plasma glycoprotein with phospholipid-binding property, is known to be the actual target antigen for autoimmune type anticardiolipin antibodies (aCLs). Certain groups of aCLs (anti-beta2GPI antibodies) exert lupus anticoagulant (LA) activity and perturb the function of vascular endothelial cells. This investigation aimed at highlighting some insights into the molecular basis by which aCLs exert their biological effects by using anti-beta2GPI mAbs with well-characterized epitopes from mice and from patients with antiphospholipid syndrome. Anti-beta2GPI mAbs directed against the third domain (Cof-20 and Cof-22) and fourth domain (Cof-21, EY1C8, and EY2C9) of beta2GPI inhibited the thrombin generation induced by Russell's viper venom in diluted plasma and that induced by the prothrombinase complex reconstituted with purified clotting factors. This anticoagulant activity was abrogated in the presence of an excess amount of phospholipids, thus resembling the LA activity. In stark contrast, anti-beta2GPI mAbs directed against the fifth domain and the carboxy-terminal region of the fourth domain showed no LA-like activity. These findings suggest that the LA activity of anti-beta2GPI antibodies depends on their epitope specificity. Experiments carried out to clarify the mechanism of the LA activity showed that anti-beta2GPI mAbs with LA-like activity, but not those without this effect, enhance the beta2GPI binding to phospholipids. In addition, the F(ab')2 fragment, but not the Fab' fragment, of the anti-beta2GPI mAbs was found to enhance the LA activity and the beta2GPI binding to phospholipids, suggesting that anti-beta2GPI antibodies induce formation of multiple complexes of beta2GPI on the surface of phospholipids because of their bivalent property. This clustering of beta2GPI molecules induced by anti-beta2GPI antibodies, probably because of their multivalent property and epitope specificity, might hinder the lateral mobility and activation of clotting factors on the surface of phospholipids and thus exert LA activity. Clustering of beta2GPI molecules may also explain the molecular mechanism by which anti-beta2GPI antibodies alter the function of leukocytes and endothelial cells. The well-documented heterogeneous LA activity of aCLs (anti-beta2GPI antibodies) may also be explained by their epitope specificity.

Animals↗
PubMed1997

Cloning and characterization of a novel gene, WS-3, in human chromosome 8p11-p12.

A novel human gene referred to as the WS-3 gene, in the short arm of human chromosome 8, was cloned by a combination of exon trapping, thermal asymmetric interlaced-PCR (TAIL-PCR) and the Marathon-Ready cDNA amplification method. The gene consists of 7 exons separated by 6 introns, and is at the telomere side of the STS marker, D8S1055. The full-length WS-3 gene contains 1052 nucleotides and codes for a protein of 190 amino acids with a calculated mol. wt. of 20,747. Southern blot experiments showed that the WS-3 gene exists as a single copy in the human genome. A protein encoded by the WS-3 gene has an R-G-D (Arg-Gly-Asp) motif in the N-terminal region, which seems to confer adhesive properties to macromolecular proteins like fibronectin. Although WS-3 is a small gene with unknown biological function, its ubiquitous expression in various tissues and organs suggests that the encoded protein is one of the essential components of all organs and tissues.

Amino Acid Sequence↗
PubMed1997

Elevation of serum creatine kinase during treatment with antithyroid drugs in patients with hyperthyroidism due to Graves disease. A novel side effect of antithyroid drugs.

We describe 4 patients with Graves disease who had abnormal increases of serum creatine kinase (CK) concentrations during treatment with antithyroid medications. Three of the patients experienced myalgia and muscle cramps. All of the patients manifested an increase in serum CK levels 1 to 3 months after the administration of antithyroid drugs. Thyrotropin concentrations and cardiac systolic time indexes during the elevation of serum CK concentrations were not consistent with hypothyroidism. The mechanisms are not obvious, but it is likely that the rapid decrease of thyroid hormones in tissues may temporarily cause hypothyroid states, resulting in alterations in CK concentrations. It is suggested that hasty correction of thyrotoxicosis should be avoided in susceptible patients, unless the thyrotoxic conditions are critical.

Adult↗
PubMed1997

Cloning and characterization of Rep-8 (D8S2298E) in the human chromosome 8p11.2-p12.

A novel human gene referred to as the Rep-8 gene (D8S2298E) was cloned by a combination of exon trapping, thermal asymmetric interlaced-PCR, and screening of a cDNA library. It is located in human chromosome 8p11.2-p12. The gene consists of eight exons and spans about 20 kb between the glutathione S-reductase and the protein phosphatase 2A beta subunit genes. The full-length Rep-8 gene contains 1483 nucleotides and codes for a protein of 270 amino acids. Southern blot experiments showed that the Rep-8 gene exists as a single copy per haploid. With a zoo blot analysis, human Rep-8 DNA hybridized strongly with the monkey DNA, but only weakly with the DNAs of species other than Homo sapiens. Northern blot analysis showed that it is expressed abundantly in the testis and ovary, suggesting that the Rep-8 gene product may play a role in reproduction.

Amino Acid Sequence↗
PubMed1997

Endothelial cells as target for antiphospholipid antibodies. Human polyclonal and monoclonal anti-beta 2-glycoprotein I antibodies react in vitro with endothelial cells through adherent beta 2-glycoprotein I and induce endothelial activation.

OBJECTIVE: To investigate the ability of human anti-beta 2-glycoprotein I (anti-beta 2 GPI) antibodies to recognize the cofactor adherent on endothelial cells (EC) and to modulate endothelial functions. METHODS: Six human affinity-purified polyclonal anti-beta 2 GPI IgG and 2 IgM monoclonal antibodies (MAb) were obtained from patients with the antiphospholipid syndrome. The antibodies were tested for their ability to 1) bind to endothelial monolayers through the adherent beta 2 GPI and 2) modulate endothelial adhesion molecule expression and interleukin-6 (IL-6) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) secretion. RESULTS: The affinity-purified IgG and the MAb with anti-beta 2 GPI activity, but not the respective controls, displayed EC binding, which declined on cells incubated in serum-free medium and was restored in a dose-dependent manner by exogenous human beta 2 GPI. After EC binding, both polyclonal and monoclonal antibodies up-regulated adhesion molecule expression. Anti-beta 2 GPI MAb also significantly increased IL-6 and 6-keto-PGF1 alpha secretion. CONCLUSION: These findings support the hypothesis that anti-beta 2 GPI antibodies bind and activate EC through the adherent cofactor beta 2 GPI, likely leading to a procoagulant state.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Mutation and haplotype analyses of the Werner's syndrome gene based on its genomic structure: genetic epidemiology in the Japanese population.

The correlation between mutations in the Werner's syndrome (WRN) gene and the haplotypes of surrounding markers was studied in Japanese patients. We have elucidated the genomic structure of WRN helicase, and found five additional mutations, designated mutations 6-10. Mutations 4 and 6 were found to be the two major mutations in this population; these mutations comprised 50.8% and 17.5%, respectively, of the total in a sample of 126 apparently unrelated chromosomes. Almost all the patients homozygous for mutation 4 shared a haplotype around the WRN gene, consistent with the view that they are derived from a single ancestor. This important advantage demonstrated in the identification of the WRN gene suggests that the Japanese present a unique population for the cloning of other disease genes. The conserved haplotype was observed across 19 loci, extending a distance estimated to be more than 1.4 Mbp around the WRN gene. This haplotype is rare among random Japanese individuals. Unexpectedly, all the nine patients homozygous for mutation 6 shared a haplotype that was identical to this haplotype at 18 of these 19 markers. These results suggest that mutations 4 and 6 arose independently in almost identical rare haplotypes. The remaining mutations (1, 5, 7, 8, 9, and 10) occurred rarely, and were each associated with different haplotypes.

DNA Helicases↗
PubMed1997

Development of a recording system for saliva pH with and complete denture by telemetry.

A new system for measuring saliva pH by radio telemetry was developed. The system was built into a lower complete denture and could operate for about 19 h. The maximum error in the range pH 5-8 was 0.15 pH, and the correlation when values were compared with those from a glass-electrode pH meter was 0.99. That this system operates successfully was confirmed in a clinical experiment.

Aged↗