Biomedical subjects

Y Tani

Publications and source records attributed to Y Tani.

At least 109 records · Page 6Linked to original sources

PubMed1997

Amyloid deposits in the gastrointestinal tract of aging dogs.

Pathologic features, immunohistochemical characteristics, and incidence of gastrointestinal amyloid deposition were investigated in 78 canine necropsies, including 43 males and 35 females ranging from 2 months to 20 years of age. In 31 of 78 dogs, amyloid protein was accumulated in or around vessel walls located in submucosal and muscular layers of the alimentary tract and mesenteric tissues. These deposits did not seem to affect the function(s) of the digestive tract histologically. The deposits showed congophilia and green birefringence under polarized microscopy. Transmission electron microscopy revealed randomly arranged amyloid fibrils 6-10 nm in diameter around a blood vessel. Congophilia was retained even after oxidation with potassium permanganate, suggesting that this protein is not the AA form of amyloid. Although immunohistochemical studies were performed using antibodies to canine amyloid apolipoprotein AI and synthetic human beta amyloid peptide, the immunochemical nature of the protein was not determined. The mean ages of both male and female dogs with gastrointestinal amyloid deposition were higher than those of their normal counterparts (P < 0.001), and the incidence of deposition in elderly dogs was higher than that in young dogs (P < 0.005). However, there was no sex predilection with respect to both the mean age of the dogs with deposition and the incidence of occurrence. The mechanism(s) and importance of this form of amyloid deposition remain unclear.

Aging↗

PubMed1997

Ester synthesis by NAD(+)-dependent dehydrogenation of hemiacetal: production of methyl formate by cells of methylotrophic yeasts.

A water-soluble ester, methyl formate, was detected as a metabolite in the culture medium of methylotrophic yeasts. Methyl formate synthase, which catalyses NAD(+)-dependent dehydrogenation of the hemiacetal adduct of methanol and formaldehyde, catalyses the ester synthesis. The enzyme activity was induced on a methanol medium and was increased further by the addition of formaldehyde. In the reaction system using intact cells of Pichia methanolica AKU 4262, 135 mM (8.1 g/liter) methyl formate was produced from 2 M methanol. This is a new biological process for ester synthesis that couples spontaneous formation of hemiacetal and alcohol dehydrogenase.

Esters↗

PubMed1997

Serum IgA1 and IgA2 subclass antibodies against collagens in patients with ankylosing spondylitis.

We measured IgA1 and IgA2 subclass antibody levels against human type I, II, III and IV collagens in patients with ankylosing spondylitis (AS) by enzyme linked immunosorbent assay (ELISA). Significant elevations of IgA1 antibodies against type II collagen (p < 0.01) and IgA2 antibodies against type I (p < 0.001), III (p < 0.001), and IV (p < 0.01) collagens were observed in AS patients compared with those of healthy controls. These findings suggest that serum IgA antibodies against type I, III and IV collagens were mainly produced in secretory lesions in AS patients.

Adult↗

PubMed1997

Antibodies to Klebsiella, Proteus, and HLA-B27 peptides in Japanese patients with ankylosing spondylitis and rheumatoid arthritis.

OBJECTIVE: To determine whether patients with ankylosing spondylitis (AS) and patients with rheumatoid arthritis (RA) from Japan have antibodies to Klebsiella pneumoniae and Proteus mirabilis and to assess whether such antibodies are activated against peptides sharing sequences with HLA-B27. METHODS: Serum samples from 152 Japanese patients, 52 with AS, 50 with RA, and 50 healthy controls, were tested against 3 bacteria (K. pneumoniae, P. mirabilis, and Escherichia coli) and 3 synthetic peptides (HLA-B27, pullulanase-D, and scrambled pullulanase-D control peptide) by ELISA under coded conditions. Samples were tested for elevations in IgG, IgA, and IgM antibody classes in patients with active AS or RA, in patients with RA with probable disease, and in patients with inactive AS. Disease activity was determined by an elevated serum C-reactive protein (> 10 mg/l) level and elevated erythrocyte sedimentation rate (> 20 mm/h). RESULTS: Patients with active AS showed specific elevations in serum IgA antibody levels against K. pneumoniae compared to patients with RA and controls (p < 0.001). No such elevation was seen in the IgG and IgM antibody classes. Patients with inactive AS showed no elevation in any class of antibody against K. pneumoniae compared to controls or patients with RA. Patients with active or probably active RA showed significant elevations in IgG antibody levels against P. mirabilis compared to AS and controls (p < 0.001). Patients with AS (active or inactive), RA (active or probably active), and controls showed no elevations in any antibody class to E. coli. Both active and inactive AS patients had specific autoantibodies against HLA-B27 peptide compared to patients with RA and controls (active AS: IgG, IgA, IgM, p < 0.001; inactive AS: IgG and IgA, p < 0.001). Patients with active AS had IgG and IgA antibodies against pullulanase-D peptide, which contains a sequence that cross reacts with HLA-B27 compared to controls (p < 0.001). CONCLUSION: These results provide the first evidence of AS and RA patients in Japan having specific elevations of antibody to K. pneumoniae and P. mirabilis, respectively. This suggests that K. pneumoniae in AS and P. mirabilis in RA may play a role in triggering and/or exacerbating these diseases.

Adult↗

PubMed1997

[Optic nerve head and choroidal circulation measured by laser Doppler flowmetry in response to intravenous administration of noradrenaline].

We investigated the change of optic nerve head blood flow (ONHBF) and choroidal blood flow (CBF) in response to noradrenaline (NA) intravenously administered in anesthetized cats. NA (0.03, 0.1, 0.3 micrograms/kg/min) was injected 5 minutes continuously via the femoral vein. The relative blood flow and systemic blood pressure were continuously measured before and after NA administration with fundus camera-based laser Doppler flowmetry. Systemic blood pressure increased by 6%, 42% and 48% according to the dose. The changes in ONHBF after NA administration were -1.4 +/- 3.5% (mean +/- standard deviation) with 0.03 micrograms/kg/min, 2.4 +/- 6.9% with 0.1 micrograms/kg/min, -2.2 +/- 4.4% with 0.3 micrograms/kg/min, respectively. It did not change significantly despite doses of NA. CBF did not change significantly with 0.03 micrograms/kg/min. CBF increased significantly by 62.7 +/- 65.4% with 0.1 micrograms/kg/min, and 80.4 +/- 73.1% with 0.3 micrograms/kg/min. These results suggest that ONHBF is autoregulated despite the change of perfusion pressure by NA administration. This response is different from that of CBF.

Animals↗

PubMed1997

[Prevalence of prolonged APTT and lupus anticoagulant in autoimmune thyroid disease].

We describe prevalences of prolonged activated partial thromboplastin time(APTT) and lupus anticoagulant(LAC) in autoimmune thyroid disease(AITD). Prolonged APTTs were observed in 33(6.2%) blood samples out of 532 AITD cases(327 Graves' diseases and 205 Hashimoto's thyroiditis), but in only 8(2.0%) samples out of 396 non AITD cases(213 thyroid tumors, 14 subacute thyroiditis and 169 normal thyroids). The samples with prolonged APTT showed no abnormality in coagulation factors(factor VIII, IX, XI, XII, von Willebrand factor(vWF), prekallikrein, or high molecular weight kininogen) or factor VIII, IX inhibitor. Among samples with prolonged APTT, LAC evaluated by platelet neutralization procedure(PNP) was positive in 17(51.5%) samples of AITD, and in 2(25.0%) samples of non AITD. In prolonged APTT cases, the frequency of fetal loss in patients with AITD was higher than non AITD patients. But no significant difference was obtained between thyroid autoimmune antibody and the frequency of fatal loss. These indicate unknown biological association of between AITD and LAC.

Abortion, Spontaneous↗

PubMed1996

Primary structures of fungal fructosyl amino acid oxidases and their application to the measurement of glycated proteins.

Fructosyl amino acid oxidase (FAOD), which is active toward model compounds of the glycated proteins in blood, N epsilon-fructosyl N sigma-Z-lysine and N-fructosyl valine, was purified to homogeneity from Aspergillus terreus GP1. Though the enzyme did not use glycated proteins directly as its substrate, it used glycated human serum albumin (HSA) when HSA was treated with a protease. Linear relationships between both the concentration and the increase in absorbance and the glycation rate of glycated HSA and the increase in absorbance were observed. cDNAs coding for FAODs were cloned from cDNA libraries of A. terreus GP1 and Penicillium janthinellum AKU 3413. The coding region for both fungal FAODs consisted of 1314 bp encoding 437 amino acids. The sequence of a dinucleotide-binding motif, GXGXXG, was in the deduced N-terminal region and a similar sequence to that the active site of bacterial sarcosine oxidases was found near the C-terminal region of FAOD. The of C-terminal tripeptides SKL and AKL of FAODs from A. terreus and P. janthinellum, respectively, represent typical peroxisomal-targeting signals. Finally, FAOD protein was produced in Escherichia coli transformants in an active form, and at the same level as in the original fungi.

Amino Acid Oxidoreductases↗

PubMed1996

Activation of JAK-STAT and MAP kinases by leukemia inhibitory factor through gp130 in cardiac myocytes.

BACKGROUND: Interleukin (IL)-6-related cytokines share gp130 as the signal-transducing protein. Downstream of gp130, two signal-transducing pathways have been recognized, the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway and the Ras-mitogen-activated protein kinase (MAPK) pathway. To determine whether these two signaling pathways through gp130 are present in cardiac myocytes, we examined their activation by using leukemia inhibitory factor (LIF), which is a member of the IL-6 cytokine family. METHODS AND RESULTS: Lysates from neonatal rat cardiac myocytes were immunoprecipitated with anti-gp130, anti-JAK1, or anti-STAT3 antibody and blotted with anti-phosphotyrosine antibody. Tyrosine phosphorylation of gp130, JAK1, and STAT3 was observed after LIF stimulation in cardiac myocytes. MAPKs were maximally activated 5 minutes after LIF stimulation. Furthermore, anti-gp130 antibody significantly inhibited the LIF-induced activation of JAK1, STAT3, and MAPKs. To examine whether these signaling pathways were also activated in the adult heart in vivo, LIF was injected intravenously into a 6-week-old mouse, and the heart was examined subsequently. gp130, STAT3, and MAPKs were activated in the heart after LIF treatment. CONCLUSIONS: These results demonstrate for the first time that a JAK-STAT pathway and a MAPK pathway are present down-stream of gp130 in cardiac myocytes and are rapidly activated by LIF both in vitro and in vivo. Activation of gp130 constitutes a novel signaling pathway in cardiac myocytes.

Animals↗

PubMed1996

Absence of fetal liver hematopoiesis in mice deficient in transcriptional coactivator core binding factor beta.

Core binding factor beta (CBF beta) is considered to be a transcriptional coactivator that dimerizes with transcription factors core binding factor alpha 1 (CBFA1), -2, and -3, and enhances DNA binding capacity of these transcription factors. CBF beta and CBFA2, which is also called acute myeloid leukemia 1 gene, are frequently involved in chromosomal translocations in human leukemia. To elucidate the function of CBF beta, mice carrying a mutation in the Cbfb locus were generated. Homozygous mutant embryos died between embryonic days 11.5-13.5 due to hemorrhage in the central nervous system. Mutant embryos had primitive erythropoiesis in yolk sac but lacked definitive hematopoiesis in fetal liver. In the yolk sac of mutant embryos, no erythroid or myeloid progenitors of definitive hematopoietic origin were detected, and the expression of flk-2/flt-3, the marker gene for early precursor cells of definitive hematopoiesis, was absent. These data suggest that Cbfb is essential for definitive hematopoiesis in liver, especially for the commitment to early hematopoietic precursor cells.

Animals↗

PubMed1996

Long-term follow-up of minimal residual disease in leukemia patients by monitoring WT1 (Wilms tumor gene) expression levels.

Thirty-one patients (27 with acute myeloid leukemia [AML], 2 with acute lymphocytic leukemia [ALL], and 2 with acute mixed lineage leukemia [AMLL]) treated with conventional chemotherapy (CHT) and 23 patients (13 AML, 5 ALL, and 5 with chronic myeloid leukemia [CML]) treated with allogeneic bone marrow transplantation (BMT) were monitored for WT1 expression levels in BM and peripheral blood (PB) by reverse transcriptase-polymerase chain reaction over a long-term period (mean, 29 months for CHT and 24 months for BMT). Sixteen of the patients in the CHT group and 3 in the BMT group who had achieved complete remission suffered clinical relapse. In 10 of these patients, WT1 expression that had returned to normal BM levels (< 10(-3); the WT1 expression level of K562 cells was defined as 1.0) after complete remission (CR) either gradually or rapidly increased again to abnormal levels 1 to 18 months (mean, 7 months) before clinical relapse became apparent. In another 9 patients, WT1 expression never returned to normal BM levels even after CR and the subsequent relapse was accompanied by a rapid increase in WT1 expression to levels higher than 10(-2) (10(-3) levels in PB). On the other hand, the remaining 35 patients (15 CHT and 20 BMT) maintained their CR. In 29 of these patients (11 CHT and 18 BMT), WT1 expression either gradually or rapidly decreased to normal BM levels, whereas in the other 6 (4 CHT and 2 BMT), low or very low levels of WT1 mRNAs (10(-3) to 10(-2) in BM and 10(-5) to 10(-3) in PB) remain detectable, but without any clinical signs of relapse. A clear correlation was found to exist between the minimal residual disease (MRD) detected in the paired BM and PB samples for all types of leukemias (AML, ALL, and CML), with MRD in PB being approximately one-tenth of that in BM. WT1 quantitation of 168 paired BM and PB samples showed that PB samples were superior to BM samples for the detection of MRD. We conclude that monitoring of WT1 expression levels in BM and PB makes it possible to rapidly assess the effectiveness of individual treatment and diagnose clinical relapse in the early stage for all leukemia patients regardless of the presence or absence of tumor-specific DNA markers.

Bone Marrow↗

PubMed1996

Effect of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin and infusion of L-tyrosine on the in vivo L-[beta-11C] DOPA disposition in the monkey brain.

The effect of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) and L-tyrosine infusion on [11C]dopamine synthesis was analyzed in the striatum of Rhesus using positron emission tomography (PET). The rate for decarboxylation from L-[beta-11C]DOPA to [11C]dopamine was calculated using a graphical method with cerebellum as a reference region. Although the peripheral administration of 6R-BH4 at low dose (2 mg/kg) did not provide a significant increase in the rate of dopamine biosynthesis, a high dose of 6R-BH4 (20 mg/kg) induced an elevation of the rate. This 6R-BH4-induced elevation of the dopamine synthesis rate was further dose-dependently enhanced by the continuous infusion of L-tyrosine (0.2 and 1.0 mumol/min/kg). L-Tyrosine infusion with a rate of 1.0 mumol/min/kg caused an enhancement of the rate even during low dose administration of 6R-BH4 (2 mg/kg). L-Tyrosine infusion alone did not induce any elevation of the dopamine biosynthesis rate. The analysis of plasma indicated that the metabolic ratios of L-[beta-11C]DOPA to each metabolite were not affected by 6R-BH4 and/or L-tyrosine infusion. The results suggest that the low dose loading of tyrosine facilitates the activity of 6R-BH4 on the presynaptic dopamine biosynthesis, and also that the combined effects can be monitored by PET using L-[beta-11C]DOPA as a biochemical probe.

Animals↗

PubMed1996

Cathepsin B in gingival crevicular fluid of adult periodontitis patients: identification by immunological and enzymological methods.

Cathepsin B (EC 3.4.22.1), a typical lysosomal cysteine proteinase was identified immunologically with anti-human cathepsin B antibody in inflammatory exudate, gingival crevicular fluid (GCF) of adult periodontitis patients. The sensitive enzyme immunoassay (EIA) system initially developed, was rarely influenced by the presence of endogenous cysteine proteinase inhibitors, cystatin(s), indicating that it is possible to quantify the gross amount of cathepsin B including free enzyme forms and enzyme-inhibitor complex forms using this EIA system. The cathepsin B levels in GCF as determined by EIA and the activity measured with Z-Arg-Arg-MCA showed positive and significant correlation with various clinical parameters. Immunoblotting analysis revealed that the molecular form was a 29 kDa mature enzyme. More than 95% of Z-Arg-Arg-MCA hydrolytic activity in each GCF sample was inhibited by CA-074, specific inhibitor of cathepsin B. These results strongly suggested that the gross amount of cathepsin B in GCF as well as its activity level is closely associated with the severity of the disease and that cathepsins B play an important role in the pathogenesis of periodontitis.

Blotting, Western↗

PubMed1996

Molecular mimicry: the geographical distribution of immune responses to Klebsiella in ankylosing spondylitis and its relevance to therapy.

The discovery that HLA-B27 is linked to ankylosing spondylitis (AS) and HLA-DR1/DR4 to rheumatoid arthritis (RA) has provided new approaches to the study of the possible causation of these diseases. Several theories have been proposed to explain these associations but only one, namely "molecular mimicry", has provided a specific aetiological agent for each of these diseases. Molecular mimicry between HLA-B27 and two molecules in Klebsiella microbes: nitrogenase and pullulanase D has been reported whilst in Proteus microbes, the haemolysin molecule shows sterochemical similarity to HLA-DR1/DR4. Elevated immune responses to Klebsiella microbes have been demonstrated in AS patients from 10 different countries and this wide geographical distribution suggests that the same aetiological agent is probably acting in producing this condition. Furthermore RA patients show similar immune responses to Proteus microbes. Whether AS or RA are caused by these bacteria can only be resolved by tissue typing all rheumatological patients early, in the course of their disease and then assessing their response to antibiotic chemotherapy in longitudinal studies involving double-blind crossover trials. It is possible that in the future, the course of AS or even RA could be modified by adequate antibiotic chemotherapy or even diets which affect the substrates on which these bacteria grow.

Antibodies, Bacterial↗

PubMed1996

[Efficiency of combination chemotherapy and interferon-alpha therapy in a patient with AIDS-related cutaneous and gastrointestinal Kaposi's sarcoma].

A 40-year-old male was admitted to the hospital with acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia (PCP). Two months before admission the patient had a high fever, general fatigue and mild epigastic tenderness. On admission, physical examination revealed numerous small tumors on the head, gingiva, neck, nasal ala, anterior forehead, anterior thoracic, bilateral sole and bilateral lower limbs. At that time, the CD4 cell count was 130/microliters. Upper GI endoscopy was performed because of sever epigastralgia and hematemesis. The gastric mucosa was diffusely nodular and erythematous with bleeding. This biopsy showed Kaposi's sarcoma, and the same findings were obtained from the duodenum, rectum and skin, AIDS with related cutaneous and gastrointestinal KS and PCP was diagnosed. We performed a combination of chemotherapy and Interferon-alpha therapy, and the KS almost completely disappeared within 3 months.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Bioconversion of 7-Aminocephalosporanic Acid by Intact Rhodotorula glutinis Cells.

When 7-aminocephalosporanic acid (7-ACA) was used as a single carbon source in the enrichment culture medium for screening 7-ACA-degrading microorganisms, pink yeast colonies appeared frequently, and these were identified as Rhodotorula glutinis. These intact R. glutinis cells converted (i) 7-ACA to deacetyl-7-ACA (7-ADACA) and (ii) monochloroacetyl-7-ACA to monochloroacetyl-7-ADACA at sufficiently high levels to be of commercial interest. Acetylation of 7-ADACA to 7-ACA, the reverse reaction of hydrolysis in an organic medium with methyl acetate as an acetyl donor, was also demonstrated.

Journal Article↗

PubMed1996

Isolation and characterization of a novel oxygenase that catalyzes the first step of n-alkane oxidation in Acinetobacter sp. strain M-1.

In the Finnerty pathway for n-alkane, oxidation in Acinetobacter sp., n-alkanes are postulated to be attacked by a dioxygenase and the product, n-alkyl hydroperoxide, is further metabolized to the corresponding aldehyde via the peroxy acid [W. R. Finnerty, P. 184-188, in A. H. Applewhite (ed.), Proceedings of the World Conference on Biotechnology for the Fats and Oil Industry, 1988]. However, no biochemical evidence regarding the first-step reaction is available. In this study, we found a novel n-alkane-oxidizing enzyme that requires only molecular oxygen, i.e., not NAD(P)H, in our isolate, Acinetobacter sp. strain M-1, and purified it to apparent homogeneity by gel electrophoresis. The purified enzyme is a homodimeric protein with a molecular mass of 134 kDa, contains 1 mol of flavin adenine dinucleotide per mol of subunit, and requires CU2+ for its activity. The enzyme uses n-alkanes ranging in length from 10 to 30 carbon atoms and is also active toward n-alkenes (C12 to C20) and some aromatic compounds with substituted alkyl groups but not toward a branched alkane, alcohol, or aldehyde. Transient accumulation of n-alkyl hydroperoxide was detected in the course of the reaction, and no oxygen radical scavengers affected the enzyme activity. From these properties, the enzyme is most probably a dioxygenase that catalyzes the introduction of two atoms of oxygen to the substrate, leading to the formation of the corresponding n-alkyl hydroperoxide. The enzymatic evidence strongly supports the existence of an n-alkane oxidation pathway, which is initiated by a dioxygenase reaction, in Acinetobacter spp.

Acinetobacter↗

PubMed1996

Molecular analysis of females manifesting thyroxine-binding globulin (TBG) deficiency: selective X-chromosome inactivation responsible for the difference between phenotype and genotype in TBG-deficient females.

T4-binding globulin (TBG) is the major transport protein of thyroid hormone in man. Inherited TBG abnormalities were manifested fully in hemizygous males and partially in heterozygous females and transmitted in an X-chromosome-linked fashion, compatible with its location on Xq21-22. We have previously reported that complete deficiency (CD) and partial deficiency (PD) in Japanese subjects resulted from two distinct mutations of the TBG gene, TBG-CDJ and TBG-PDJ, respectively. Recently, we encountered a female manifesting TBG-CD and herein investigated the molecular mechanisms. She was found to possess TBG-CDJ and common-type TBG (TBG-C) alleles by characterizing the TBG gene. Then, X-chromosome inactivation status was evaluated in her family members using a phosphoglycerate kinase (PGK) gene, located on Xq13. Three TBG-CDJ heterozygotes and one unaffected female, confirmed to be PGK heterozygotes for a polymorphic BstXI site, were analyzed. Only the CD female was shown to undergo selective inactivation by examining the BstXI site in amplified products after digestion with a methylation-sensitive enzyme, HpaII. Among an additional eight informative females with TBG deficiency, one heterozygous female for TBG-PDJ shared this selective inactivation pattern. Moreover, the X-chromosome with TBG-C was suggested to be inactivated selectively from the linkage of PGK and TBG alleles recognized in eight of nine family members. Selective X-chromosome inactivation was considered to be the cause of a female heterozygous for TBG-CDJ or -PDJ manifesting the same phenotype as a hemizygote.

Base Sequence↗

PubMed1996

Production of fructosyl lysine oxidase from Fusarium oxysporum S-1F4 on autoclave-browned medium.

In Fusarium oxysporum S-1F4, fructosyl lysine oxidase (FLOD) was induced with N epsilon-fructosyl N alpha-Z-lysine (epsilon-FL), which is a model compound of a glycated protein, and the induction was inhibited by the addition of cycloheximide in the growing cells. FLOD formation was greatly enhanced in an autoclave-browned medium containing glucose and L-lysine. Some Amadori compounds formed from glucose and L-lysine during autoclaving were assumed to induce the enzyme. After optimization of the culture conditions, FLOD produced in the browned medium was comparable to that in the medium with epsilon-FL.

Amino Acids↗