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Biomedical subjects

K Ichikawa

Publications and source records attributed to K Ichikawa.

At least 55 records · Page 3Linked to original sources
PubMed2001

Mannose-binding lectin gene: polymorphisms in Japanese patients with systemic lupus erythematosus, rheumatoid arthritis and Sjögren's syndrome.

Mannose-binding lectin (MBL) is a key element of the innate immunity, with a structure similar to complement C1q. Serum MBL levels are greatly affected by the polymorphisms of the MBL gene. In particular, codon 54 mutation of the MBL gene results in a significant reduction of serum MBL. To determine whether polymorphism of the MBL gene is associated with occurrence of systemic lupus erythematosus (SLE), rheumatoid arthritis and Sjögren's syndrome in the Japanese population, we analyzed the MBL gene polymophisms of these patients and controls, by polymerase chain reaction-restriction fragment length polymorphism methods. We found that patients studied had a significantly higher frequency of having homozygous codon 54 mutation compared to controls. In particular, patients with SLE or Sjögren's syndrome showed higher probabilities of being homozygous for this mutation. Among subjects with the same genotype, SLE patients tended to have higher serum MBL concentration than controls. Analysis of the promotor region suggested that SLE patients heterozygous for the codon 54 mutation have a higher probability of having a low producing haplotype for the gene without the codon 54 mutation. We conclude that persons homozygous for codon 54 mutation of the MBL gene may be prone to occurrence of autoimmune disorders including SLE, in the Japanese. MBL may have protective effects on occurrence and progression of SLE.

Arthritis, Rheumatoid↗
PubMed2001

Molecular cloning, expression and modelling of cat allergen, cystatin (Fel d 3), a cysteine protease inhibitor.

BACKGROUND: Cats are an important source of indoor allergens. However, only two cat allergens, Fel d 1 and albumin, have been cloned and sequenced. IgE antibodies to Fel d 1 and albumin do not fully account for IgE responses to cat and there is good immunochemical evidence that cats produce other allergens. OBJECTIVE: To identify and define the molecular structure of the other potential cat allergens. METHODS: A cat skin cDNA library was screened using pooled serum obtained from five asthmatic patients which contained high levels of IgE antibody to cat dander. Selected cDNA clones were screened by plaque immunoassay and one cDNA clone, encoding cystatin, was expressed in E. coli. The three dimensional structure of cat cystatin was modelled using the SWISS-MODEL computer program. RESULTS: Three positive cDNA clones (A, B and C) were identified, two of which were fully sequenced. Clones A and C encoded the same 98 amino acid residue sequence which showed 79% and 75% homology with bovine and human cystatin A, respectively. The cat cystatin sequence contained the conserved cysteine protease inhibitor signature and two of three lipocalin motifs. By plaque immunoassay, 60-90% of cat allergic sera had IgE ab to the expressed cystatin clones. The cysteine protease inhibitor motif was also partially conserved in dog allergen sequences, Can f 1 and Can f 2, which are lipocalins. The recombinant protein was expressed in E. coli as an 11-kDa protein, corresponding to the predicted MW of cat cystatin. The three-dimensional structure of cat cystatin was modelled on human cystatin structures. CONCLUSION: A newly identified allergen, cystatin (Fel d 3), has been cloned from cat skin and is a member of the cysteine protease inhibitor family.

Allergens↗
PubMed2001

Detection of 'antiphospholipid' antibodies: a single chromogenic assay of thrombin generation sensitively detects lupus anticoagulants, anticardiolipin antibodies, plus antibodies binding beta(2)-glycoprotein I and prothrombin.

The diagnosis of the antiphospholipid syndrome (APS) requires both a typical clinical event plus a persistently positive test in an assay for either anticardiolipin (aCL) antibodies or a lupus anticoagulant (LA). Enzyme linked immunosorbent assays (ELISA) specific for autoantibodies against beta(2)-glycoprotein I (beta(2)GPI) or prothrombin are also used, but none of the tests are adequately sensitive or specific. A chromogenic assay was developed that measures the effect of test antibody or plasma samples on in vitro thrombin formation. It is able to detect both LA and beta(2)GPI-dependent aCL antibodies and may have greater specificity for APS than currently available tests. Using this method various monoclonal antibodies (MoAbs) were examined, from mice immunized with beta(2)GPI, mice with a spontaneous animal model of APS, and from three humans with APS. Plasma and affinity purified antibodies from patients with APS and control groups were also examined. Thrombin inhibition was more sensitive to perturbation by MoAbs than a combination of tests for LA (P < 0.05) and at lower antibody concentrations (12.5 microg/ml versus 100 microg/ml). There was a significant correlation between inhibition of thrombin generation and the level of MoAb reactivity to beta(2)GPI (r = 0.90; P < 0.001) but not to CL (r = 0.06; P = 0.76). Plasma and affinity purified antibodies from patients with APS also inhibited thrombin generation, and significantly more so than patients with aPL from causes other than APS. APS patient samples showed thrombin inhibition in the presence of anti-beta(2)GPI or antiprothrombin antibodies. All MoAbs binding beta(2)GPI showed inhibition of thrombin generation, while MoAbs binding domain I of beta(2)GPI had more LA effect.

Animals↗
PubMed2001

Suppressive effects of oxcarbazepine on tooth pulp-evoked potentials recorded at the trigeminal spinal tract nucleus in cats.

1. The purpose of the present study was to evaluate the antinociceptive effect of oxcarbazepine, a keto derivitive of carbamazepine (an anticonvulsant), in an animal model. To evoke a nociceptive response, we electrically stimulated the maxillary canine tooth pulp (MCTP) in anaesthetized (allobarbital-urethane), spontaneously breathing cats. 2. The evoked potentials were recorded from the superficial layers of the caudal part of the trigeminal spinal tract nucleus (5ST). We examined a slow component with a large amplitude (the P3 component) in evoked compound potentials; its mean conduction velocity was 1.7 m/s, suggesting a response mediated by C-fibres. 3. To confirm that the P3 component was related to pain sensation, we used morphine, a most efficacious antinociceptive agent, in the present study. The P3 component was significantly suppressed by intravenous administration of morphine (3 mg/kg) and was also suppressed by microinjection of morphine (2 microg) into the recording site of the 5ST. These results suggest that the P3 component is involved in the transmission of nociceptive information. 4. We compared the effect of oxcarbazepine with mexiletine; both are known to block neuronal Na+ channels. Intravenous administration of mexiletine suppressed the P3 component at a dose of 5 mg/kg. Microinjection of mexiletine (10 microg) into the recording site of the 5ST tended to suppress the P3 component, but this effect was not significant. 5. Intravenous administration of oxcarbazepine (1-10 mg/kg) caused a dose-dependent inhibition of the P3 component, which was significantly suppressed at 10 mg/kg oxcarbazepine. Intravenous administration of 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (MHD), a metabolite of oxcarbazepine, at doses of 3-30 mg/kg caused a dose-dependent inhibition of the P3 component. Oxcarbazepine was not available for the microinjection study because it is not water soluble. We used MHD for the microinjection study instead of oxcarbazepine, because MHD can be dissolved in water up to 3 mg/mL. Microinjections of MHD (6 microg) into the recording site of the 5ST suppressed the P3 component. These results indicate that oxcarbazepine has an antinociceptive action.

Analgesics, Opioid↗
PubMed2001

Proliferation and release of IL-5 and IFN-gamma by peripheral blood mononuclear cells from cat-allergic asthmatics and rhinitics, non-cat-allergic asthmatics, and normal controls to peptides derived from Fel d 1 chain 1.

BACKGROUND: In general, T cells from normal, nonatopic individuals respond to aeroallergens with synthesis and release of IFN-gamma. In contrast, release of T(H)2-type cytokines by activated lymphocytes is a feature of allergic rhinitis and atopic asthma. OBJECTIVE: The purpose of this study was to determine differences in T-cell recognition of epitopes within allergenic sequences, in terms of proliferation and cytokine production, in subjects with atopic asthma compared with subjects with allergic rhinitis and normal controls. METHODS: Proliferative responses and IL-5/IFN-gamma release patterns from PBMCs from cat-allergic asthmatic, cat-allergic rhinitic, and non-cat-allergic asthmatic subjects and nonatopic normal controls were determined in primary cultures. Cells were challenged with 7 overlapping peptides spanning chain 1 of the major cat allergen, Fel d 1. RESULTS: The 4 groups did not differ with respect to the ability to mount proliferative responses to Fel d 1 peptides. In all groups, the IFN-gamma responses were predominantly to the amino terminus peptides. Cat-allergic and non-cat-allergic asthmatic subjects (and not cat-allergic rhinitic subjects and normal controls) made IL-5 responses to most of the Fel d 1 peptides, the result being a mixed (T(H)0) cytokine response at the N-terminus and a restricted (T(H)2) response at the C-terminus. CONCLUSION: Proliferative and IL-5/IFN-gamma responses of T cells from asthmatic and atopic rhinitic subjects and normal controls to allergen peptides can be dissociated. Furthermore, differing cytokine responses to peptides derived from a single antigen suggest that certain domains of the molecule might preferentially induce IL-5 rather than IFN-gamma and as a result could be more important in disease pathogenesis.

Adult↗
PubMed2001

A-Cell: graphical user interface for the construction of biochemical reaction models.

SUMMARY: A-Cell is a tool for constructing models of complex and complicated biochemical reactions. An important feature of A-Cell is its graphical user interface for constructing biochemical reactions. In addition, it has a capability of importing previously constructed models, combining them, and constructing a comprehensive model. The simulation program for the model is automatically generated by A-cell.

Biochemistry↗
PubMed2001

Effect of KAD-1229, a nonsulfonylurea hypoglycemic agent, on plasma glucose and insulin in streptozotocin-induced diabetic dogs.

Hypoglycemic agents with a rapid onset and short duration of action should be useful for controlling postprandial hyperglycemia. Our aim was to establish a diabetes mellitus model in dogs, and then during an oral glucose tolerance test to compare the hypoglycemic effect and insulinotropic action of KAD-1229, a new hypoglycemic agent, with that of gliclazide, a conventional sulfonylurea. In this model, KAD-1229 reduced the increase in plasma glucose level without producing hypoglycemia. Gliclazide had a weaker effect on reduction of the glucose increase and caused hypoglycemia via a significantly raised insulin secretion in the late phase. A rapid insulinotropic action of KAD-1229 was clearly observed in the portal venous blood. The results suggest that in type 2 diabetes caused by, at least, insulin deficiency, KAD-1229 may improve impaired insulin secretion in the early phase and attenuate hyperglycemia without causing a sustained hypoglycemia.

Animals↗
PubMed2001

[Pharmacological effects of cabergoline against parkinsonism].

The pharmacological effects of cabergoline, a novel ergot alkaloid, against parkinsonism were assessed by comparing its effects with those of bromocriptine and pergolide. The affinities of cabergoline and pergolide for the D2 receptor were about the same, about 7 times stronger than that of bromocriptine. The affinity of each compound for the D1 receptor was markedly lower than its affinity for the D2 receptor. However, other data suggest that cabergoline and pergolide would have D1-receptor agonist activity, whereas bromocriptine would act as a D1-receptor antagonist. In MPTP-lesioned parkinsonian monkeys, cabergoline improved motor disability, and its effect lasted longer than those of bromocriptine and pergolide. Moreover, cabergoline induced no behavioral abnormalities even though at the highest dose used, in contrast to bromocriptine and pergolide, both of which induced hyperactivity. This beneficial effect of cabergoline did not attenuate on prolonged administration. Combined treatment with a low dose of L-dopa and a low dose of cabergoline improved motor disability without inducing the hyperactivity and dyskinesia seen during treatment with L-dopa alone at high doses. From these results, we suggest that cabergoline promises to be a useful anti-parkinsonian agent with a long lasting effect that survives prolonged administration and without the side effects induced by L-dopa.

Animals↗
PubMed2001

Structures of Thermoactinomyces vulgaris R-47 alpha-amylase II complexed with substrate analogues.

The structures of Thermoactinomyces vulgaris R-47 alpha-amylase II mutant (d325nTVA II) complexed with substrate analogues, methyl beta-cyclodextrin (m beta-CD) and maltohexaose (G6), were solved by X-ray diffraction at 3.2 A and 3.3 A resolution, respectively. In d325nTVA II-m beta-CD complex, the orientation and binding-position of beta-CD in TVA II were identical to those in cyclodextin glucanotransferase (CGTase). The active site residues were essentialy conserved, while there are no residues corresponding to Tyr89, Phe183, and His233 of CGTase in TVA II. In d325nTVA II-G6 complex, the electron density maps of two glucosyl units at the non-reducing end were disordered and invisible. The four glucosyl units of G6 were bound to TVA II as in CGTase, while the others were not stacked and were probably flexible. The residues of TVA II corresponding to Tyr89, Lys232, and His233 of CGTase were completely lacking. These results suggest that the lack of the residues related to alpha-glucan and CD-stacking causes the functional distinctions between CGTase and TVA II.

Cyclodextrins↗
PubMed2001

Assessment of abdominal aortic aneurysms using a cone-beam CT system: an experimental phantom study and an initial clinical evaluation before and after stent-graft treatment in patients with an abdominal aortic aneurysm.

The aim of this study is to conduct a quantitative analysis of cone-beam CT (CBCT) images using a phantom, and then to evaluate the clinical usefulness of CBCT in the assessment of abdominal aortic aneurysms (AAA) before and after stent-grafting, both qualitatively as well as quantitatively. The phantom used in this study was a rectangular plate made of an acrylic resin, which contained eight through-holes to mimic blood vessels. Each columnar cavity was filled with contrast media and the diameter of each was then measured using a cone-beam multiplanar reformation/curved planar reformation (CB-MPR/CPR) technique, and the results were compared with the corresponding results obtained by actual measurement. In the clinical assessment, nine patients with AAA (consisting only of males with an average age of 68 years old: 56 approximately 80) were enrolled. The clinical qualitative analysis of CBCT consisted of: 1) for the pre-operative state, the shape of the aortic aneurysm, the relationship between the aneurysm and the aortic branches, and 2) for the post-operative state, the shape of the stent and any endoleakage present. The clinical quantitative analysis of CBCT included, for the aneurysm, its inflection angle, its maximum diameter, the diameter of the proximal and distal necks, and the distance of these two necks from specific reference points. The quantitative analysis using the phantom showed no significant differences between the results based on CB-MPR/CPR and those obtained by actual measurement. In the clinical qualitative analysis three-dimensional CBCT (3D-CBCT) depicted the anatomical relationship between the aneurysm and the aortic branches well, an accomplishment that was not possible by conventional angiography. Cone-beam maximum intensity projection (CB-MIP) was as good in tracing the migration and deformation of the stent following endovascular intervention as plain radiograms and conventional angiograms. CB-MPR/CPR enabled us to obtain any cross-sectional image of the aorta desired, including a curved, longitudinal cross-section of the aorta. Thus, with the CB-MPR/CPR technique it is easy to determine the distance of the proximal and distal necks of the aneurysm, and the inflection angle, and those results were not significantly different from those obtained by angiography. The diameter of the aneurysm, and the diameter of the proximal and distal necks as measured by CB-MPR/CPR images were significantly different from those obtained by conventional contrast enhanced-CT (p<0.05). This suggests that CB-MPR/CPR yields a cross-sectional view that is more perpendicular to the longitudinal direction of the aorta than that given by conventional contrast enhanced-CT, and thus provides a more accurate cross-sectional image of the aneurysm than the latter. We conclude that, in the experimental phantom study CBCT had a high quantitative reliability, and that, in the clinical study CBCT provided useful information for both qualitatively and quantitatively evaluating AAA before and after stent-grafting.

Aged↗
PubMed2001

IgA-kappa type multiple myeloma affecting proximal and distal renal tubules.

A 45-year-old male was admitted because of chest pain, lumbago, and bilateral ankle pain. Examination disclosed hypophosphatemic osteomalacia, acquired Fanconi syndrome, and abnormalities in distal nephron such as distal renal tubular acidosis and renal diabetes insipidus. Further exploration revealed IgA kappa multiple myeloma excreting urinary Bence Jones protein (kappa-light chain). Renal biopsy revealed thick basement membranes and elec-tron-dense crystals in proximal tubular epithelial cells. Immunofluorescent studies revealed deposition of kappa-light chain in renal tubular epithelial cells that caused the renal tubular damage. Although the osteomalacia was relieved by medical treatment, the urinary Bence Jones protein and the renal tubular defects were not improved by the chemotherapy for the myeloma. The patient died of exacerbation of multiple myeloma at 50 years of age.

Biopsy↗
PubMed2001

Cytokine production inhibitors produced by a fungus, Oidiodendron griseum.

A series of diterpenes were isolated from the fermentation broth of a fungus, Oidiodendron griseum CL37215. The diterpenes were identified as LL-Z1271alpha, LL-Z1271gamma, CJ-14,445, PR 1388, CJ-14,604 and a new diterpene, CJ-14,515. They inhibited both lipopolysaccharide-induced interleukin-1beta and tumor necrosis factor-alpha production in human whole blood with IC50s of the range from 0.049 to 100 microM.

Ascomycota↗
PubMed2001

Novel cytokine production inhibitors produced by a basidiomycete, Marasmiellus sp.

New cytokine production inhibitors, CJ-14,877 (I) and CJ-14,897 (II), were isolated from the fermentation broth of a basidiomycete, Marasmiellus sp. CL21624. Their structures were determined to be methyl-(7S,8S)-5-(7,8-dihydroxypropyl)pyridine-2-carboxylate and methyl-(7S,8S)-5-(8-acetoxy-7-hydroxypropyl)pyridine-2-carboxylate [corrected], respectively, by spectroscopic analyses. These compounds showed inhibitory activities for lipopolysaccharide-induced production of interleukin-1beta and tumor necrosis factor-alpha in human whole blood with IC50 values of the range from 0.059 to 2.6 microM.

Agaricales↗
PubMed2001

Anticardiolipin antibody assay: a methodological analysis for a better consensus in routine determinations--a cooperative project of the European Antiphospholipid Forum.

Despite the widely recognized practical importance of anticardiolipin (aCL) ELISA, the reliability of this test has been recently discussed. In order to investigate this area on European scale, we sent to 30 experienced centers a questionnaire focusing on the diagnostic procedures applied to patients with antiphospholipid syndrome (APS) and on the detailed protocols used to perform aCL. Anticardiolipin ELISA was found to be the most frequently performed test in patients with suspected APS, but significant difference was shown among the various protocols. The cross-laboratory multiple examination of ten serum samples evaluated independently by the 24 centers pointed out the difficulty in getting comparable results. Therefore a "consensus" protocol was derived from the aCL methods giving the best performance. The materials and reagents necessary to perform the "consensus" method, including, as putative standards, one IgG and one IgM monoclonal antibody (HCAL and EY2C9) were distributed to 19 Centers. The results of one IgG and one IgM aCL high positive sera measured in serial dilutions were compared. A progressive decrease in the variability of the values obtained for a given sample appeared evident when all the laboratories used the same standard, in their own in-house ELISA and even more in the "consensus" ELISA. Our data show that aCL ELISA standardization is necessary in order to obtain comparable results in different laboratories.

Adult↗
PubMed2001

Beta-catenin expression as a prognostic indicator in cervical adenocarcinoma.

The purpose of this study was to assess the prognostic influence of beta-catenin expression by immunohistochemistry in patients with cervical adenocarcinomas. The study group comprised of 51 patients who underwent total hysterectomy for cervical cancer. The median follow-up was 39 months (range 1-138 months). beta-catenin was expressed strongly on the membranes of normal cervical epithelial and glandular cells. Uniform membranous beta-catenin staining localized to intercellular borders was observed in 35% of tumors, whereas 65% of tumors demonstrated an abnormal pattern of reduced or aberrant beta-catenin expression (i.e., cytoplasmic and/or nuclear staining patterns). Abnormal beta-catenin immunoreactivity was associated statistically with advanced pathologic stage (p=0.018). The 10-year disease-free survival was 51.0% in patients with preserved expression of beta-catenin. On the other hand, a poorer prognosis was noted in the group with abnormal expression of beta-catenin with a 10-year disease-free survival of 43.4%. By multivariate analysis, low pathologic stage (stages I and II, p=0.001) and preservation of beta-catenin expression (p=0.012) were independently favorable prognostic factors. Our results indicate that changes in beta-catenin expression occur during the progression of cervical adenocarcinoma to an invasive phenotype. These results suggest that beta-catenin is an important intercellular adhesion molecule. Assessment of beta-catenin immunoreactivity may be a useful prognostic tool in cervical adenocarcinoma complementary to established prognostic factors. Furthermore, we developed a strategy for choosing biomarkers representing the steps in malignant progression in an effort to identify patients with occult metastases who will need adjuvant therapy and spare women from unnecessary interventions.

Adenocarcinoma↗