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Biomedical subjects

T Takayanagi

Publications and source records attributed to T Takayanagi.

At least 37 records · Page 2Linked to original sources
PubMed1999

Electrophoretic mobility study on ion-ion interactions in an aqueous solution.

Ion-ion interactions between anions and their pairing ions in aqueous solutions were studied through the measurements of electrophoretic mobilities of analyte ions in capillary zone electrophoresis, where the electrophoretic method for the analysis of ion association reaction is shown to be more useful than the conductometric method widely used in the analysis of the reactions. The electrophoretic mobility of monovalent inorganic anions was almost identical even when the concentrations of alkali metal ions and quaternary ammonium ions in the migrating solution were varied up to 15 mM. On the other hand, the electrophoretic mobility of organic anions, such as monovalent and divalent anions, decreased with increasing concentrations of quaternary ammonium ions. Changes in the electrophoretic mobilities were analyzed by a non-linear least-squares method giving ion association constants. The results indicate that the proposed method is applicable to the analysis of such reactions to give the mobility change. The ion association constants obtained in an aqueous solution were related to the extraction constants of the ion associates, and the contributions of the association process and the distribution process were clarified.

Acids↗
PubMed1999

Modulation by endothelin-1 of lipopolysaccharide-induced cyclooxygenase 2 expression in mouse peritoneal macrophages.

We investigated the modulation by endothelin-1 of lipopolysaccharide-induced cyclooxygenase 2 expression and prostaglandin E2 production by mouse peritoneal macrophages. Our previous report showed that endothelin-1 at concentrations above 10(-11) M induced cyclooxygenase 2 expression through mainly endothelin ET(B) receptors and that an endothelin ET(B) receptor-mediated process was not involved in cyclooxygenase 2 activation in macrophages stimulated by lipopolysaccharide for 4 h. In the present study, when macrophages were stimulated by lipopolysaccharide for 12 h in the presence of endothelin-1 (10(-15) to 10(-8) M), cyclooxygenase 2 expression and prostaglandin E2 production were enhanced by 1.2- to 1.6-fold. The endothelin ET(B) receptor selective antagonist, BQ788 (N-cis-2,6-dimethylpiperidino-carbonyl-L-gamma-methyl-leucyl-D-L-m ethoxycarbonyl-tryptophanyl-norleucine), significantly inhibited this synergistic effect of endothelin-1. In addition, the cyclooxygenase 2-selective inhibitor, NS398 (N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide), also suppressed this effect. Western blot analysis showed that the endothelin ET(B) receptor was up-regulated by lipopolysaccharide in a time- and concentration-dependent manner, and that this up-regulation was inhibited by NS398. From these results, we conclude that endothelin-1 promotes lipopolysaccharide-induced cyclooxygenase 2 activation in the delayed phase through endothelin ET(B) receptors up-regulated by lipopolysaccharide.

Animals↗
PubMed1999

Development of an apparatus for monitoring protoplast isolation from plant tissues based on both dielectric and optical methods.

In order to develop a method allowing objective determination of the optimal conditions for the isolation of protoplasts, the process of protoplast isolation from plant tissues was quantitatively evaluated. First, a specialized spectrophotometer cuvette (working volume = 2.0 ml) was designed for the continuous monitoring of protoplast isolation from plant tissues based on the optical method. Homogeneous mixing of tissue sections and the protoplast suspension in the cuvette was accomplished by means of a magnetic bar. The cuvette was divided into upper and lower parts by a nylon mesh. Since tissue sections in the upper part could not pass through the mesh, they did not affect the optical path in the lower part, and only isolated protoplasts were able to move freely between the two parts. At the optimal agitation speed (200 rpm), mechanical damage to protoplasts of Catharanthus roseus did not occur. Increases in the protoplast concentration during their isolation from tissue sections (leaf and petal) could be continuously monitored by measuring the optical density (O.D.), making it possible to estimate the end of protoplast isolation. Degassing treatment of the tissues markedly enhanced protoplast isolation. In order to monitor the viable protoplast concentration, a larger specialized spectrophotometer cuvette (working volume = 25 ml) was developed which enabled simultaneous measurement of the permittivity and O.D. of the suspension to be carried out during protoplast isolation. Permittivity is a measure of the viable protoplast concentration, while the O.D. shows protoplast characteristics such as color. Using this large cuvette, the time courses of protoplast isolation from leaf and petal sections were monitored and large amounts of viable protoplasts were obtained. The protoplast isolation process after degassing treatment was described by a simple first-order reaction model and the viable protoplast isolation rate was quantitatively evaluated from the rate constant (k) on the basis of permittivity changes.

Journal Article↗
PubMed1999

Response of skin blood volume, velocity and flow to local warming in newborns, measured by laser Doppler flowmetry.

BACKGROUND: In order to know the response of the skin microcirculation to local warming, we determined changes in the skin blood volume (Vol), velocity (Vel) and flow (F) by using a new laser Doppler device on newborns. METHODS: The study subjects were 39 infants whose gestational age was 34.1 +/- 2.8 weeks and birth weight was 2189 +/- 572 g. The study was performed from 8 h postnatally to 28 postnatal days. We measured skin blood volume, velocity and flow at 36 degrees C (Vol36, Vel36, F36), and each value at 5 min (Vol44-5, Vel44-5, F44-5) and 10 min (Vol44-10, Vel44-10, F44-10) after local warming was applied at 44 degrees C and the response curve of each parameter was obtained. Subsequently, serial changes in the response of skin microcirculation to local warming were investigated in nine very low birth weight (VLBW) infants (28.3 +/- 0.9 weeks, 1150 +/- 148 g) and 12 low birth weight (LBW) infants (32.8 +/- 1.3 weeks, 1971 +/- 292 g). The F36, the increment rate of blood volume (delta Vol) and the increment rate of blood velocity (delta Vel) were obtained within 24 h, from day 1 to day 7 and from day 8 to day 30 in both VLBW and LBW infants and from day 31 to day 60 and at more than 61 days in VLBW infants. The F36, delta Vol and delta Vel were compared during the study periods in VLBW and LBW infants. All results were expressed as mean +/- SD. RESULTS: The results showed that F36/F44-10 and F44-5/F44-10, Vol36/Vol44-10 and Vol44-5/Vol44-10, Vel36/Vel44-10 and Vel44-5/Vel44-10 were 0.25 +/- 0.09 and 0.74 +/- 0.17, 0.58 +/- 0.14 and 0.94 +/- 0.08, 0.42 +/- 0.12 and 0.79 +/- 0.15, respectively. Different modes of delivery did not have a significant effect on this response. The F36 in VLBW infants was high during the early neonatal period and gradually decreased with postnatal age. The delta Vol was low in VLBW infants during the neonatal period and gradually increased. The F36 in VLBW1-7 was significantly higher than in LBW1-7 (P < 0.01) and full-term controls (P < 0.001). The delta Vol in VLBW1-7 was 0.26 +/- 0.23, which is significantly lower than in LBW1-7 (0.57 +/- 0.17, P < 0.001) and full-term controls (0.77 +/- 0.21, P < 0.001). The delta Vel in VLBW1-7 and LBW1-7 was significantly higher than in controls (P < 0.05). CONCLUSIONS: The skin blood flow increased continuously when local warming was applied at 44 degrees C. This high blood flow and limited potential of vasodilatation are the characteristics of the skin microcirculation in VLBW infants during the neonatal period.

Blood Flow Velocity↗
PubMed1999

Transgenic mice harboring a full-length human mutant DRPLA gene exhibit age-dependent intergenerational and somatic instabilities of CAG repeats comparable with those in DRPLA patients.

Dentatorubral-pallidoluysian atrophy (DRPLA) is one among an increasing number of hereditary neurodegenerative diseases determined as being caused by unstable expansion of CAG repeats coding for polyglutamine stretches. To investigate the molecular mechanisms underlying CAG repeat instability, we established three transgenic lines each harboring a single copy of a full-length human mutant DRPLA gene carrying a CAG repeat expansion. These transgenic mice exhibited an age-dependent increase (+0.31 per year) in male transmission and an age-dependent contraction (-1.21 per year) in female transmission. Similar tendencies in intergenerational instabilities were also observed in human DRPLA parent-offspring pairs. The intergenerational instabilities of the CAG repeats may be interpreted as being derived from the instability occurring during continuous cell division of spermatogonia in the male, and that occurring during the period of meiotic arrest in the female. The transgenic mice also exhibited an age-dependent increase in the degree of somatic mosaicism which occurred in a cell lineage-dependent manner, with the size range of CAG repeats being smaller in the cerebellum than in other tissues including the cerebrum, consistent with observations in autopsied tissues of DRPLA patients. Thus, the transgenic mice described in this study exhibited age-dependent intergenerational as well as somatic instabilities of expanded CAG repeats comparable with those observed in human DRPLA patients, and are therefore expected to serve as good models for investigating the molecular mechanisms of instabilities of CAG repeats.

Adult↗
PubMed1999

Effects of phosphodiesterase inhibitors on cytokine production by microglia.

Type III and IV phosphodiesterase inhibitors (PDEIs) have recently been shown to suppress the production of TNF-alpha in several types of cells. In the present study, we have shown that all the types of PDEIs, from type I- to V-specific and non-specific, suppress the production of TNF-alpha by mouse microglia stimulated with lipopolysaccharide (LPS) in a dose-dependent manner. Certain combinations of three different types of PDEIs synergistically suppressed TNF-alpha production by microglia at a very low concentration (1 microM). Since some PDEIs reportedly pass through the blood-brain barrier (BBB), the combination of three PDEIs may be worth trying in neurological diseases, such as multiple sclerosis and HIV-related neurological diseases in which TNF-alpha may play a critical role. Some PDEIs also suppressed interleukin-I (IL-I) and IL-6 production by mouse microglia stimulated with LPS. In contrast, the production of IL-10, which is known to be an inhibitory cytokine, was upregulated by certain PDEIs. The suppression of TNF-alpha and induction of IL-10 were confirmed at the mRNA level by RT-PCR. PDEIs may be useful anti-inflammatory agents by downregulating inflammatory cytokines and upregulating inhibitory cytokines in the central nervous system. (CNS).

1-Methyl-3-isobutylxanthine↗
PubMed1999

[A case of acute transverse myelopathy and bilateral optic neuritis associated with anticardiolipin antibodies, lupus anticoagulant and perinuclear antineutrophil cytoplasmic antibodies].

A 69-year-old woman developed paraplegia and hypesthesia on upper extremities and below T4 level. Examination of cerebrospinal fluid showed increased protein levels and pleocytosis. MRI of the cervical spinal cord revealed syrinx formation from C3 to upper thoracic cord. A diagnosis of acute transverse myelitis was made. A high dose of corticosteroid including pulse therapy did not improve her symptoms and signs of myelopathy, but the syrinx could not be found thereafter. One year later, she developed severe visual loss due to bilateral optic neuritis which was improved spontaneously. The clinical course and MRI findings were similar to those of the optic-spinal form of multiple sclerosis (MS). The presence of anticardiolipin antibodies, lupus anticoagulant and perinuclear anti-neutrophil cytoplasmic antibodies, however, strongly suggested that vasculitic and/or ischemic mechanisms induced by these autoantibodies might play a role on the development of the disease. We conclude that our case should be distinguished from MS.

Acute Disease↗
PubMed1999

[A case with HTLV-I associated myelopathy (HAM) accompanied by primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH)].

We reported a 60-year-old female patient with HTLV-I associated myelopathy (HAM) accompanied by primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH). The diagnosis of PBC and AIH was confirmed by liver biopsy. HAM is considered to be mediated by cellular immune mechanisms, while humoral immune mechanisms may play a predominant role in the development of PBC and AIH. Flowcytometric analysis of lymphocyte subset of peripheral blood was within normal limits. We then collected CD4 positive cells from the patient. These cells expressed T helper 2 (Th 2) cytokine mRNA such as IL-4 and IL-10, but did not express Th 1 cytokines, indicating the predominance of Th 2 in this patient. This case suggested the possibility that disease associated Th 2 might develop in the course of Th1-mediated disease like HAM.

Female↗
PubMed1998

Cyclooxygenase 2 expression by endothelin-1-stimulated mouse resident peritoneal macrophages in vitro.

Macrophages have been shown to produce endothelin and to play a role in the pathogenesis of neural damage after cerebral ischemia or vasospasm after subarachnoid hemorrhage. Cyclooxygenase 2 is induced during inflammation following brain insult and participates in inflammation-mediated neurotoxicity. However, it has not yet been established how endothelin-1 acts on cyclooxygenase 2 expression in macrophages. In the present study, we examined the effects of endothelin-1 on cyclooxygenase 2 expression and prostaglandin E2 production, and the effects of endothelin ET(A) and ET(B) receptor antagonists. Stimulation by endothelin-1 ranging from 10(-11) to 10(-9) M time and dose dependently increased the production of prostaglandin E2 and the expression of cyclooxygenase 2 protein without changing that of cyclooxygenase 1 protein, an effect which was inhibited by dexamethasone, nonsteroidal anti-inflammatory drugs and the selective endothelin ET(B) receptor antagonist, BQ788 (N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methyl-leucyl-D-L-me thoxycarbonyl-tryptophanyl-D-norleucine). The selective endothelin ET(A) receptor antagonist, BQ123 [cyclo (D-Trp-D-Asp-Pro-D-Val-Leu)] also inhibited these reactions, but its potency was less than that of the selective endothelin ET(B) receptor antagonist. Endothelin ET(A) and ET(B) receptor antagonists had no effects on cyclooxygenase 2 protein expression and prostaglandin E2 production in lipopolysaccharide-stimulated macrophages. We conclude that endothelin-1 increases cyclooxygenase 2 protein expression and prostaglandin E2 production via mainly endothelin ET(B) receptors and partly endothelin ET(A) receptors in macrophages; however, lipopolysaccharide increases both cyclooxygenase 2 protein expression and prostaglandin E2 production in pacrophages without involving endothelin ET(A) or ET(B) receptor-mediated processes.

Animals↗
PubMed1998

Intrathymic selection of NK1.1(+)alpha/beta T cell antigen receptor (TCR)+ cells in transgenic mice bearing TCR specific for chicken ovalbumin and restricted to I-Ad.

Generation and negative selection of NK1.1(+)alpha/beta T cell receptor (TCR)+ thymocytes were analyzed using TCR-transgenic (B10. D2 x DO10)F1 and (C57BL/6 x DO10)F1 mice and Rag-1(-/-)/DO10 mice, which had been established by breeding and backcrossing between Rag-1(-/-) and DO10 mice. Almost all T cells from these mice were shown to bear Valpha13/Vbeta8.2 that is specific for chicken ovalbumin (cOVA) and restricted to I-Ad. A normal proportion of the NK1.1(+) Valpha13/Vbeta8.2(+) thymocytes was generated in these mice. However, the actual cell number of both NK1.1(+) and NK1.1(-) thymocytes in I-Ad/d mice (positive selecting background) was larger than that in I-Ab/d mice (negative selecting background). Markedly low but significant proportions of NK1.1(+) Valpha13/Vbeta8.2(+) cells were detected in the spleens from I-Ad/d and I-Ab/d mice. It was shown that the splenic NK1.1(+) T cells of the I-Ab/d mice were anergized against stimulation through TCR. When (B10.D2 x DO10)F1 and (C57BL/6 x DO10)F1 mice were given cOVA, extensive or intermediate elimination of NK1.1(+)alpha/betaTCR+ thymocytes was induced in I-Ad/d or I-Ab/d mice, respectively. However, the clonal elimination was not as complete as that seen in the major NK1.1(-) thymocyte population. The present findings indicate that normal generation of NK1.1(+)alpha/betaTCR+ thymocytes occurs in the absence of Valpha14-Jalpha281 and that substantial negative selection operates on the NK1.1(+)alpha/betaTCR+ cells.

Animals↗
PubMed1998

Production of interleukin-12 and expression of its receptors by murine microglia.

Production of interleukin-12 (IL-12) by cultured murine microglia and astrocytes was examined, by means of ELISA to detect heterodimeric p70 and RT-PCR to analyze the expression of mRNA encoding p35 and p40. Microglia, but not astrocytes, produced IL-12 p70 in response to lipopolysaccharide and interferon-gamma. The microglial cell line, Ra2, produced only p40, but not p35, upon above stimulation. Thus, it is possible that some population of microglia induce helper 1 type T cell response via producing IL-12 in the CNS. Microglia were induced to express mRNA encoding IL-12 receptors which were exclusively expressed in activated T and NK cells.

Animals↗
PubMed1998

Complete-type DiGeorge syndrome treated by bone marrow transplantation.

BMT was carried out on a patient with DiGeorge syndrome who suffered recurrent infections after birth. At 13 months of age, 8.0 x 10(8)/kg of bone marrow nuclear cells were infused from an HLA-identical sibling using only anti-thymocyte globulin to prevent rejection. Donor DNA was not detected on microsatellite polymorphism by PCR. At 19 months of age, a second BMT from the same donor was carried out using busulfan and cyclophosphamide as conditioning. DNA examination of bone marrow showed chimerism at day 18 and complete donor origin at day 28. Seven months post-BMT, the numbers of CD3-, CD4- and CD8-positive cells were in the normal range. BMT is thus an effective therapy for DiGeorge syndrome.

Antigens, CD↗
PubMed1998

Bullous pemphigoid associated with Shy-Drager syndrome.

We report a patient with Shy-Drager syndrome who developed multiple tense blisters mainly on the extremities. Circulating anti-basement membrane zone autoantibodies were detected by the indirect immunofluorescence method. Immunoblot analysis using normal human epidermal extracts demonstrated that this patient's serum reacted only with 230 kD bullous pemphigoid antigen (BPAG1). Concerning the pathoetiology of the association of bullous pemphigoid and Shy-Drager syndrome, we discuss a sequence similarity between BPAG1 and dystonin, a candidate gene for dystonia musculorum.

Autoantibodies↗
PubMed1998

CAG repeat expansions in patients with sporadic cerebellar ataxia.

CAG repeat expansions cause spinocerebellar ataxia type 1 (SCA1), SCA2, SCA3, SCA6 and dentatorubral-pallidoluysian atrophy (DRPLA). So far these expansions have been examined mainly in ataxia patients with a family history. However, some sporadic cases with SCA have recently been reported. To elucidate the frequency and characteristics of sporadic SCAs, we screened 85 Japanese ataxia patients without a family history for the SCA1, SCA2, SCA3, SCA6 and DRPLA mutations. As a result, 19 patients (22%) were found to have expanded CAG repeats. Among sporadic SCAs, the SCA6 mutation was most frequently observed. The sporadic SCA6 patients had smaller CAG repeats and a later age of onset than SCA6 patients with an established family history. We also identified one father-child pair in which intermediate sized CAG repeats expanded into the SCA2 disease range during transmission. These findings suggest that patients with ataxia even without a family history should be examined for a CAG repeat expansion.

Age Factors↗
PubMed1998

Propentofylline inhibits production of TNFalpha and infection of LP-BM5 murine leukemia virus in glial cells.

We examined the effects of a xanthine derivative, propentofylline, on TNFalpha production by glial cells and on infection ofglial cells with a murine leukemia virus, LP-BM5, which induces murine AIDS in susceptible mice. Propentofylline suppressed TNFalpha production in glial cells and also effectively suppressed infection ofglial cells with LP-BM5 in vitro. Addition ofTNFalpha, but not IL-1 or IL-6, abolished the suppressive effects ofpropentofylline. Anti-TNFalpha antibody also suppressed infection of LP-BM5 in these cells. These findings suggest that propentofylline suppressed LP-BM5 infection in glial cells by suppressing TNFalpha production by these cells. Because propentofylline reportedly passes through the blood-brain barrier, it may be useful in the treatment of central nervous system involvement by HIV infection or neurological diseases in which TNFalpha plays a causative role, such as multiple sclerosis.

Animals↗
PubMed1998

Identification of a new fluke allergen identified by monoclonal IgE antibodies for Paragonimus miyazakii.

IgE-producing hybridomas were acquired from fusing splenic cells to myeloma cells of BALB/c mice infected with Paragonimus miyazakii. With the use of the monoclonal antibody (mAb)xIgE obtained, the localization of the allergen in P. miyazakii, as well as its molecular weight, was evaluated. The allergen was present in the gut epithelium and luminal contents of adult flukes. Because this allergen was absent in the related species Paragonimus westermani and Paragonimus ohirai, we believe that it is specific to P. miyazakii. The allergen was estimated to be less than 14,400 daltons and was 1 of the smallest components that appeared after electrophoresis.

Allergens↗
PubMed1998

[A case of acute multifocal motor neuropathy with conduction block after Campylobacter jejuni enteritis].

The patient was a 25-year-old male with acute multifocal motor neuropathy with conduction block (MMNCB) after Campylobacter jejuni enteritis. After having suffered from diarrhea for 3 days, he rapidly developed asymmetrical distal-dominant muscle weakness in all extremities. Sensory disturbance was unremarkable except for slight disturbance in deep sensation. Deep tendon reflexes were normal throughout the course of present illness. CSF analysis revealed increased protein up to 66 mg/dl without pleocytosis. In electrophysiological examinations, persistant multifocal conduction blocks in the motor nerves were predominantly noted in the distal part of the extremities. Serum titers of anti-Campylobacter jejuni antibody, anti-GM1 antibody and anti-GalNAc-GD1a antibody were elevated. Muscle weakness resolved completely within 7 weeks. The sural nerve biopsy did not reveal either axonal degeneration, nor demyelination. These clinical and laboratory findings suggested that this case was most likely an acute type of MMNCB after Campylobacter jejuni enteritis.

Acute Disease↗