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Biomedical subjects

C Tanaka

Publications and source records attributed to C Tanaka.

At least 145 records · Page 8Linked to original sources

[Hemolytic anemias observed in SLE].

Hemolytic anemia observed in patients with SLE include autoimmune hemolytic anemia (AIHA) and thrombotic microangiopathic hemolytic anemia (TMHA). AIHA is caused by anti-erythrocyte antibody, which can be detected by direct Coombs' test. Recently, anti-phospholipid antibody draw attention as a cause of AIHA in SLE. TMHA include thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Patients with TTP show CNS symptoms and renal damage, while those with HUS develop renal insufficiency, but show minimal CNS symptoms. Clinical findings of TMHA are fever, hemolytic anemia, thrombocytopenia, CNS symptoms, and renal insufficiency, which are quite same as the findings of SLE itself. TMHA should be considered for differential diagnosis in acute exacerbation of SLE.

Anemia, Hemolytic↗

Flow cytometric platelet enumeration utilizing monoclonal antibody CD42a.

We investigated a flow cytometric method with monoclonal antibody CD42a as a potential reference method for platelet enumeration by blood count analysers. Using peripheral blood samples from 25 healthy individuals we obtained significant (P < 0.0001) correlations between the results obtained by a FACScan method and similar cell counters (TOA Medical Electronics, Kobe, Japan): r = 0.960 (FACScan vs SSF), r = 0.958 (FACScan vs SE-9000A,B), r = 0.949 (FACScan vs K-4500A) and r = 0.954 (FACScan vs K-4500B). This flow cytometric method for counting platelets using the monoclonal antibody CD42a can be used to check the calibration of the platelet count by blood cell analysers.

Antibodies, Monoclonal↗

Low cerebrospinal fluid concentrations of peptide histidine valine and somatostatin-28 in Alzheimer's disease: altered processing of prepro-vasoactive intestinal peptide and prepro-somatostatin.

Recent studies have indicated that deposition of beta amyloid peptide in the brains of patients with senile dementia of the Alzheimer type (SDAT) is a consequence of abnormal processing of the beta amyloid protein precursor. In addition, reduced concentrations of various peptides have been measured in post-mortem brain tissue and cerebrospinal fluid (CSF) of patients with SDAT. We determined concentrations of the peptides derived from prepro-vasoactive intestinal peptide (VIP)--peptide histidine methionine-27 (PHM-27), peptide histidine valine (PHV) and VIP--and peptides derived from prepro-somatostatin (prepro-SS), SS-14 and SS-28, in CSF of patients with SDAT by radioimmunoassay combined with high performance liquid chromatography. We found significantly reduced levels of total PHM-immunoreactivity (IR) and PHV, and unaltered levels of PHM-27 and VIP in SDAT, compared with those in controls. Total SS-IR and SS-28 concentrations were significantly reduced in SDAT, while SS-14 levels did not differ from those of controls. These results suggest that an altered processing of the prepro-peptides of VIP and SS may occur in SDAT and that these alterations might have a significant role in the pathogenesis of SDAT.

Aged↗

Evaluation of radioiodinated iodoclorgyline as a SPECT radiopharmaceutical for MAO-A in the brain.

An in vivo estimation of the newly synthesized MAO-A specific inhibitor, [125I]-labeled N-[3(2,4-dichloro-6-iodophenoxy)propyl]-N-methyl-2- propynylamine ([125I]-iodoclorgyline), was performed. Retention of the radioactivity of this radioligand was observed in the brain from 1 h post-injection. Pretreatments with clorgyline and l-deprenyl showed selective binding of [125I]-iodoclorgyline to MAO-A in the brain at 24 h post-injection. Moreover, a good correlation (r = 0.907) between the uptake of [125I]-iodoclorgyline and MAO-A enzyme activity in the cortex was observed in the pretreatment study with several doses of clorgyline. Although improvement to increase the brain/blood ratio is desirable because of slow blood clearance of the radioactivity, radioiodinated iodoclorgyline may serve as a useful SPECT radiopharmaceutical for quantitative analysis of MAO-A in the brain.

Animals↗

Non-invasive measurement of brain activity using functional MRI: toward the study of brain response to acupuncture stimulation.

We studied functional MRI in 15 male and 13 female normal volunteers on a clinical MRI system using gradient echo sequence. During the experiments, brain activation was induced by grasping the unilateral hand once or twice a second for motor tasks. A localized increase of MRI signal in the contralateral motor cortex was observed in 17 out of 21 cases (81%) under right hand motor task and 11 out of 21 cases (52%) under left hand motor task. The application of this method may be useful to evaluate brain response to acupuncture.

Acupuncture Therapy↗

Tumor-specific mutations in the tyrosine kinase domain of the RET proto-oncogene in pheochromocytomas of sporadic type.

Sporadic pheochromocytomas, sporadic medullary thyroid carcinomas (MTCs), pheochromocytomas and/or MTCs in multiple endocrine neoplasia (MEN) 2A or 2B were screened for mutations in the tyrosine kinase domain of the RET proto-oncogene by direct sequencing of PCR-amplified products or sequencing subcloned DNAs from PCR-products. All tumors of 4 MEN 2B patients were confirmed to contain a heterozygous missense mutation at codon 918 (ATG-->ACG; Met-->Thr) of the RET proto-oncogene as well as their leukocytes. The same tumor-specific mutations at codon 918 were also found in 5/16 (31%) sporadic pheochromocytomas. These results suggest that mutations of the RET proto-oncogene in its tyrosine kinase domain play a role not only as the predisposing gene for MEN 2B, but also as a tumorigenic factor for pheochromocytomas of sporadic type.

Adolescent↗

Thoracic flexion myelopathy. Case report.

A case of thoracic flexion myelopathy is reported in a 36-year-old man. The patient had a history of gradually progressing transverse thoracic myelopathy. Conventional myelography in the neutral position failed to reveal cord compression; however, a severe block of the dye column was evident on studies in the flexed position. Excellent recovery from this condition was obtained with posterolateral fusion of the thoracic spine in the neutral position.

Adult↗

[Long-term analysis of hypertension in men by job type].

Health education intervention for hypertension require the assessment of hypertension. Risk factors for developing hypertension in Japanese workers were evaluated by the type of occupation: manager, office worker, salesperson, blue-collar worker, and engineer. A cohort of 2,257 male subjects, aged 21 through 63 years, who were normotensive, diastolic blood pressure less than 90 mm Hg and systolic blood pressure less than 140 mm Hg in the initial year, were followed for 15 years to observe the occurrence of hypertension. Hypertension was defined as a systolic blood pressure (SBP) of 160 mm Hg or higher and/or a diastolic blood pressure (DBP) of 95 mm Hg or higher, or the initiation of antihypertensive therapy. Eight risk factors related to hypertension (age, body mass index, cigarette smoking, job characteristic, alcohol consumption, stress, SBP, and DBP) were selected for analysis using Cox proportional hazards models. Stepwise model was utilized to incorporate risk factors for each type of occupation (p < 0.05). The following results were obtained: 1. The incidence of hypertension over 15-year analysis was 29.3% for the total male subjects. 2. Each type of occupation had a different pattern of risk factors for hypertension. 3. Blood pressure at baseline showed a significant association in all types of occupation, indicating a stronger relationship with hypertension than other factors. 4. Stress and age were significantly associated in managers, salespersons, and blue-collar workers. 5. Body mass index and alcohol consumption were significantly associated in salespersons. 6. Cigarette smoking was significant in managers and blue-collar workers, with the hazard ratio in managers being greater than 1 (1.66, 95%CI 1.06-2.60) but less than 1 in blue-collar workers (0.31, 95%CI 0.15-0.67). 7. In all types of occupation, job characteristic failed to reach statistical significance. Work-site primary prevention of hypertension should be performed specifically considering type of occupation. Individual risk assessment and lifestyle modification are potentially important tools for health education in the work-site and by applying this model to primary preventive care, appropriate preventive activities specific to an individual may be developed and provided.

Adult↗

Immunocytochemical localization of the alpha-, beta I-, beta II- and gamma-subspecies of protein kinase C in the monkey visual pathway.

We examined the distribution of alpha-, beta I-, beta II- and gamma-subspecies of protein kinase C (PKC) in the monkey visual pathway, including the retina, the lateral geniculate nucleus (LGN) and the visual cortex (area 17). In the retina, alpha-PKC immunoreactivity was found in cone photoreceptor and in bipolar cells. beta I-PKC immunoreactivity was present in the ganglion cell layer and the optic nerve fibers. The beta II- and gamma-PKCs were not found in the retina. In the LGN, intense gamma-PKC immunoreactivity was found in a part of magno and parvo cells. The LGN was negative for the alpha-, beta I- and beta II-PKC. All four PKC subspecies were present in the visual cortex but the distribution was distinct. The beta I-PKC immunoreactive cells were scattered in all layers, while the alpha-PKC immunoreactive cells were prominent in layers II, III, IVb, IVc and VI, and the beta II-PKC immunoreactive cells were found in layers II, III, IVb and VI. The intense gamma-PKC immunoreactivity was present in the neuropils in layers I, IVa, IVc and VI and also in soma and dendrites in layers II and VI. It thus seems likely that each subspecies plays a specific role in neuronal transmission in the visual pathway.

Amino Acid Sequence↗

Alpha-, beta II- and gamma-subspecies of protein kinase C localized in the monkey hippocampus: pre- and post-synaptic localization of gamma-subspecies.

Protein kinase C (PKC) has attracted wide attention as a key enzyme for the expression of long-term potentiation in the hippocampus, a basic model for memory. It is of interest to study the detailed localization of PKC subspecies in the monkey hippocampus. We used immunocytochemistry to examine the localization of PKC subspecies in the hippocampus of the monkey, Macaca mulatta. Subspecies of PKC in the monkey could be separated by hydroxyapatite chromatography and the elution profile proved to be similar to that of the rat. Antibodies against each alpha, beta II and gamma-subspecies of the rat specifically reacted with the respective subspecies of monkey PKC. The alpha-, beta II- and gamma-subspecies were distinctly distributed in the hippocampus. The beta I-subspecies was not evident in the hippocampus. While both the alpha- and gamma-subspecies immunoreactive pyramidal cells were distributed throughout the hippocampus (CA1-CA3), the beta II-subspecies immunoreactive cells were scattered only in the CA1 region. The gamma-subspecies was found in granule cells and dendrites in the dentate gyrus, in mossy fibers and in their terminals in the CA3 region. The alpha-subspecies was also present in granule cells and in the dendrites but not in the mossy fibers. Glial cells did not stain with any of the antibodies used. Electron microscopy clearly showed that the gamma-subspecies was localized in both presynaptic terminals and post-synaptic dendrites. These observations suggest that subspecies of PKC in the monkey hippocampus may be involved in distinct functions and that the gamma-subspecies of PKC may act pre- and post-synaptically in pyramidal cells of the hippocampus.

Amino Acid Sequence↗

Maleimidoethyl 3-(tri-n-butylstannyl)hippurate: a useful radioiodination reagent for protein radiopharmaceuticals to enhance target selective radioactivity localization.

In pursuit of radiolabeled monoclonal antibodies (mAbs) with rapid urinary excretion of radioactivity from nontarget tissues, radioiodinated mAbs releasing a m-iodohippuric acid from the mAbs in nontarget tissues were designed. A novel reagent, maleimidoethyl 3-(tri-n-butylstannyl)hippurate (MIH), was synthesized by reacting N-(hydroxyethyl)maleimide with N-Boc-glycine before coupling with N-succinimidyl 3-(tri-n-butylstannyl)benzoate (ATE). MIH possessed a maleimide group for mAb conjugation and a butylstannyl moiety for high-yield and site-specific radioiodination, and the two functional groups were linked via an ester bond to release m-iodohippuric acid. To investigate the fate of radiolabels after lysosomal proteolysis, hepatic parenchymal cells were used as a model nontarget tissue and 131I-labeled MIH was conjugated with galactosyl-neoglycoalbumin (NGA). Further conjugation of [131I]MIH with a mAb against osteogenic sarcoma (OST7) after reduction of its disulfide bonds was followed up. In murine biodistribution studies, [131I]MIH-NGA exhibited rapid accumulation in the liver followed by radioactivity elimination from the liver at a rate that was identical to and faster than those of 131I-labeled NGA via direct iodination ([131I]NGA) and [131I]ATE-labeled NGA, respectively. While [131I]NGA indicated high radioactivity levels in the murine neck, stomach, and blood, such increases in the radioactivity count were not detectable by the administration of either [131I]MIH-NGA or [131I]ATE-NGA. At 6 h postinjection of [131I]MIH-NGA, 80% of the injected radioactivity was recovered in the urine. Analyses of urine samples indicated that m-iodohippuric acid was the sole radiolabeled metabolite. In biodistribution studies using [131I]-MIH-OST7 and [131I]ATE-OST7, while both 131I-labeled OST7s registered almost identical radioactivity levels in the blood up to 6 h postinjection, the former demonstrated a lower radioactivity level than [131I]ATE-OST7 in nontarget tissues throughout the experiment. Such chemical and biological characteristics of MIH would enable high target/nontarget ratios in diagnostic and therapeutic nuclear medicine using mAbs and other polypeptides.

Albumins↗

Potassium and calcium channel involvement in induction of long-lasting synaptic enhancement by calyculin A, a protein phosphatase inhibitor, in rat hippocampal CA1 region.

In the Schaffer collateral-CA1 pathway in rat hippocampal slices, exposure to calyculin A induced a long-lasting potentiation of the extracellular field potentials with a transient increase in glutamate release. The synaptic enhancement produced by calyculin A was blocked by staurosporine and nicardipine, but not by D,L-2-amino-5-phosphonovalerate. In dissociated CA1 pyramidal cells, calyculin A blocked the action-potential repolarization and fast after-hyperpolarization, and increased spike frequency. These results suggest that calyculin A-induced long-lasting potentiation is triggered by the blockade of Ca(2+)-activated K+ channels, the transient increase of glutamate release and the consequent activation of voltage-gated Ca2+ channels, and is maintained by increases in protein kinases activities.

Animals↗

Interaction of tacrolimus(FK506) and its metabolites with FKBP and calcineurin.

Tacrolimus(FK506) is a strong immuno-suppressant and shows its activity through inhibiting IL-2 mRNA transcription by forming pentameric complex with intracellular receptor(FK506 binding protein 12 kDa or FKBP12), Ca2+, calmodulin, and calcineurin. Here, we report the binding activity to FKBP12, the pentameric complex formation and Con-A response inhibiting activities of 7 metabolites. C15-demethylated metabolite(M-3) needed higher quantity to compete in Con-A assay and in pentamer formation assay, although it binds more strongly to FKBP12. The result suggests that the ability to form a pentameric complex is not a two step reaction with the first binding to FKBP12, but a single step reaction by components for the pentamer formation.

Animals↗

Protein phosphatase inhibitors induce the release of serotonin from rat basophilic leukemia cells (RBL-2H3).

Effects of okadaic acid (OA) and calyculin-A (CL-A), selective inhibitors of protein phosphatases 1 (PP1) and 2A (PP2A), on the release of serotonin from the rat basophilic leukemia cell line (RBL-2H3) were investigated. Both OA and CL-A induced the long-lasting release of serotonin in an extracellular Ca(2+)-independent manner. CL-A did not increase intracellular Ca2+ concentration in the fura-2-loaded cells. CL-A was 100-fold more potent than OA in inducing the release, suggesting that PP1 is a dominant protein phosphatase in regulating RBL-2H3 cells. The CL-A-induced release of serotonin was completely inhibited by the nonselective protein kinase inhibitors, staurosporine and K-252a. CL-A induced phosphorylation of several cellular proteins in RBL-2H3 cells, which could be inhibited by staurosporine. These findings suggest that the release of serotonin is subject to tonic, Ca(2+)-independent, inhibition by PP1 in RBL-2H3 cells.

Alkaloids↗

cDNA cloning of an alternatively spliced isoform of the regulatory subunit of Ca2+/calmodulin-dependent protein phosphatase (calcineurin B alpha 2).

A cDNA encoding the regulatory subunit of Ca2+/calmodulin-dependent protein phosphatase, calcineurin B (CNB), was isolated from a rat testis cDNA library. It differs from the cDNA obtained from a rat brain cDNA library by an addition of 138 base pairs in the coding region. The codon of the clone from a testis library corresponding to the initiation codon of the clone from a brain library is not ATG but AAG, 5'-noncoding regions of these cDNAs are also different. The addition in the coding region results in the gain of 46 amino acids at the N-terminus. These findings suggest that two distinct isoforms of CNB alpha are derived from the same gene through a process involving alternative utilization of two promoters. We designate the brain type isoform as CNB alpha 1 and the longer isoform as CNB alpha 2. Northern blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blot analysis suggest that CNB alpha 2 is specifically expressed in the testis, and its expression is developmentally regulated.

Amino Acid Sequence↗