Search PubMed⌕ Search

Biomedical subjects

T Hosoya

Publications and source records attributed to T Hosoya.

At least 217 records · Page 12Linked to original sources

Synergistic stimulatory effect of glucocorticoid, EGF and insulin on the synthesis of ribosomal RNA and phosphorylation of nucleolin in primary cultured rat hepatocytes.

Effects of dexamethasone, EGF and insulin on the synthesis of rRNA and phosphorylation of nucleolin in primary cultures of adult rat hepatocytes were studied. Hepatocytes were incubated for 8 h with EGF (20 ng/ml) plus insulin (0.1 microM) and/or for 20 h with dexamethasone (1 microM) before the end of incubation. The incorporation of [3H]uridine into acid-insoluble materials and the nuclear activity of RNA polymerase I were stimulated approx. 2-fold with EGF plus insulin and these were further enhanced 2-3-times by dexamethasone, although dexamethasone alone exerted no stimulation. When hepatocytes were incubated with [32P]orthophosphate, similar enhancement by these hormones was also observed in the phosphorylation of a nucleolar protein, nucleolin, which was detected by immunoprecipitation with anti-nucleolin antibodies. The amount of nucleolin was slightly increased by EGF plus insulin in the presence of dexamethasone, but scarcely changed by treatment with EGF plus insulin or dexamethasone alone. Cycloheximide inhibited RNA synthesis to a greater or lesser degree in the case of all hepatocytes which were cultured with or without these hormonal treatments. These results indicate that the in vivo effect of glucocorticoid on rRNA synthesis and nucleolin phosphorylation in liver is primarily a direct action on parenchymal cells and requires other growth factors such as EGF and insulin.

Animals↗

Autoantibodies to nucleolin in systemic lupus erythematosus and other diseases.

The 110-kDa intracellular phosphoprotein (110K) described previously by this laboratory as a common IgM autoantigen in SLE and certain other systemic autoimmune disorders and viral infections is identified as nucleolin in the present investigation. Using rabbit antiserum to rat nucleolin as a probe, IgM autoantibody-reactive 110K co-migrated with human lymphocyte nucleolin in one- and two-dimensional immunoblots. Rabbit anti-nucleolin also specifically depleted autoreactive 110K from detergent lysates of human cells. Because nucleolin shares amino acid sequence similarity and/or forms dynamic particles with other prominent autoantigens, the present observation raises the possibility that the nucleolin/anti-nucleolin system may be of special significance for the development of humoral autoreactivity to nuclear Ag.

Antibody Specificity↗

Thoracic myelopathy caused by ossification of the ligamentum flavum. Clinicopathologic study and surgical treatment.

The authors reviewed 14 patients with thoracic myelopathy caused by ossification of the ligamentum flavum (OLF). The predominant locality of symptomatic OLF was at the thoracolumbar junction, particularly at T10-11 followed by T11-12. At the level of the thickest OLF in each patient, there were three types of OLF from computed tomography and operative findings: a lateral type in 3 patients, diffuse in 8, and thickened nodular in 3. The diagnosis of OLF-related thoracic spinal canal stenosis was best made by enhanced computed tomography. Histologic study revealed that the developmental mode of OLF was mainly endochondral ossification. Numerous fibrocartilaginous cells were found in the increased and swollen collagen fibers forming the hypertrophic ligamentum flavum (HLF). Ossification extended along the superficial layer of HLF. The size or extension of OLF was relevant to the corresponding diathesis of spinalhyperostosis. Results of laminectomy for OLF were poor because of the high occurrence of complications early on or later deterioration. Therefore, laminoplasty is recommended as a successful procedure for OLF-related thoracic myelopathy, avoiding further local mechanical stress due to tensile force.

Female↗

Anti-thyroid peroxidase antibodies in sera from healthy subjects and from patients with chronic thyroiditis: differences in the ability to inhibit thyroid peroxidase activities.

A significant percentage (6.4%) of healthy subjects was found to contain anti-thyroid peroxidase (TPO) antibodies in their sera. However, in contrast with IgG from sera of patients with chronic thyroiditis, IgG from sera of healthy subjects did not inhibit TPO activities both in guaiacol and iodide assays. In addition, anti-TPO antibodies from healthy subjects did not block the inhibition of enzyme activities by anti-TPO antibodies from patients. These findings suggest that anti-TPO antibodies from healthy subjects do not bind to the epitopes relating to substrate-combining sites of TPO. Thus, the specificities of anti-TPO antibodies in healthy subjects may differ from those in cases of chronic thyroiditis.

Adult↗

Application of improved coupling assay method for peroxidase of diseased thyroids: report of three cases.

Recently we have developed an assay method for peroxidase-catalyzed coupling of iodotyronine residues of thyroglobulin, which is applicable to human diseased thyroid tissues. In the present study, the assay method as well as usual peroxidase assay methods were applied to thyroids of three patients (No. 1: familial goiter with impaired thyroglobulin synthesis, No. 2: mild chronic thyroiditis, No. 3: dyshormonogenetic goiter) who showed organification of iodine with high TSH levels and low thyroid hormone levels in sera. In general, these patients showed relatively high activities measured by guaiacol oxidation assay, iodide oxidation and coupling assay compared with those of control thyroids. Iodothyronine content in thyroglobulin was very low except thyroxine in No. 2. These results indicate that factors other than peroxidase may be responsible for the cause of the hypothyroid state. The coupling assay method used here is therefore useful for the detection of the 'coupling defect' in patients in a hypothyroid state.

Adolescent↗

In vivo effect of thyrotropin on intracellular translocation of thyroid peroxidase in rat thyroid cells by an indirect immunofluorescence method.

The in vivo effect of thyrotropin (TSH) on the intracellular localization of thyroid peroxidase (TPO) in rat thyroid epithelial cells was examined by an indirect immunofluorescence method. The staining for TPO in the epithelial cells of normal rats appeared all over the cytoplasm, especially in the apical region. The injection of propylthiouracil for 3-10 days increased the staining in the apical region. The administration of L-thyroxine for 7-10 days to normal rats abolished the relatively high localization of TPO in the apical region, and resulted in TPO staining all over the cytoplasm. Six hours after TSH was injected into the thyroxine-treated rats, localization of TPO staining in the apical region was observed. These results suggest that TSH may play a role in the translocation of preexisting TPO to the apical region before TSH-induced biosynthesis becomes evident.

Animals↗

[A study on treatment of hyperuricemia--effects and kinetics of allopurinol and oxipurinol].

In order to study the effects and pharmacokinetics of allopurinol (hereafter abbreviated to allo.) and oxipurinol (hereafter abbreviated to oxi.) six normal human subjects were given a single oral dose of either allo. (300mg) or oxi. (600mg), followed by serial determinations of serum and urinary levels of allo., oxi., uric acid, hypoxanthine (hereafter abbreviated to hx.) and xanthine (hereafter abbreviated x.) over a six-hour period. With a dose of 300mg of allo. or 600mg of oxi., the patterns of serum uric acid were similar. When 300mg of allo. was given, however, a reduction in the serum uric acid level occurred earlier. Additionally, it was found that urinary excretion of oxi. generally paralleled the plasma concentration. Allo. administration resulted in rises in plasma concentration of x., and urinary excretion of x. and hx. Oxi. administration, on the other hand, did not cause significant changes in the plasma content of x. or urinary excretory volume of hx. Only a slight increase was noted in the amount of x. excreted in the urine. When allo. was compared against oxi., pharmacokinetics of oxypurines, especially x. were found to differ markedly. The results suggested that differences in the reaction sites, varied intra- and extra-cellular distributions of allo. and oxi., and different effects on purine biosynthesis contribute to the aforementioned discrepancies.

Adult↗

[D-penicillamine induced myasthenia gravis in a patient with rheumatoid arthritis].

We have encountered a 53 year-old female with myasthenia gravis (MG) possibly induced by the treatment with D-penicillamine (D-pc). She has had a long-standing history of rheumatoid arthritis (RA) prior to the onset of MG. The diagnosis for MG was made based on the clinical findings and tests including antiacetylcholine receptor antibody and EMG. Although the drug had been efficacious for RA, it was discontinued after the development of MG. The symptoms and signs for MG were immediately disappeared, whereas clinical manifestations for RA was relapsed shortly after. Since D-Pc has been frequently used for the treatment of RA, an awareness of this side effect appears to be of particular importance for physicians in clinical practice who deal with RA. Furthermore, it may also provide some important immunological insights into the study of pathogenesis of MG.

Arthritis, Rheumatoid↗

Treatment of cervical spondylotic myelopathy by enlargement of the spinal canal anteriorly, followed by arthrodesis.

Thirty-seven patients who had enlargement of the spinal canal anteriorly and stabilization of the spine for cervical spondylotic myelopathy were followed for an average of forty-nine months (range, twenty-eight to seventy months). Myelography and computed tomographic myelography were performed preoperatively on all patients to determine the location and features of the areas of decompression. The canal was enlarged by discectomy; by subtotal corpectomy and removal of the anteromedial parts of the pedicles; or by removal of osteophytes or of the posterior longitudinal ligament, or both. Partial corpectomy and interbody arthrodesis was performed in nine patients; subtotal corpectomy, including removal of the posterior parts of the vertebral bodies and of the posterior longitudinal ligament, and strut bone-grafting, in fifteen patients; and subtotal corpectomy, with detachment of the remaining thin posterior parts of the vertebral bodies and of the posterior longitudinal ligament, and strut bone-grafting, in thirteen patients. Postoperatively, radiographic examinations, including myelography and computed tomographic myelography, were performed for thirty-six patients and magnetic resonance imaging, for twenty-eight. A satisfactory neurological result was obtained in twenty-nine patients. Atrophy of the spinal cord, as seen on preoperative computed-tomographic myelograms, was predictive of an unsatisfactory result of the decompression, as was weakness of the peroneal muscles. All but one of the thirty-seven patients had improved walking ability at the most recent follow-up examination: seventeen patients improved by 1 point; fourteen, by 2 points; four, by 3 points; and one, by 4 points. The remaining patient reverted to the preoperative status after an initial improvement. The ability to walk at the interim examinations was compared with that at the most recent examination; three patients had continuing improvement, while three others had deterioration. The main cause of deterioration was new spondylotic changes associated with stenosis of the spinal canal, occurring at the level of the disc just cephalad to the fused levels. We concluded that anterior decompression followed by a secure arthrodesis should be an extensive procedure for patients who have cervical spondylotic myelopathy, as determined preoperatively from a myelogram or computed tomographic myelogram. Excision of the vertebral bodies should also be wide and should include the anteromedial parts of the pedicles. The third or fourth cervical vertebra should be included in the arthrodesis prophylactically in patients who have stenosis of the spinal canal when either of these vertebrae is adjacent to the level of fusion.

Adult↗

Kinetic and molecular orbital studies on the rate of oxidation of monosubstituted phenols and anilines by horseradish peroxidase compound II.

The second-order rate constant (k4) for the oxidation of a series of aromatic donor molecules (monosubstituted phenols and anilines) by horseradish peroxidase (HRP) compound II was examined with a stopped-flow apparatus. The electronic states of these substrates were calculated by an ab initio molecular orbital method. It was found that in both phenols and anilines log k4 values correlate well with the highest occupied molecular orbital (HOMO) energy level and the lowest unoccupied molecular orbital (LUMO) energy level, but not with the net charge or frontier electron density on atoms of these molecules. The HOMO and LUMO energy levels of phenols and anilines further showed linear relationships with Hammett's sigma values with negative slopes. Similar results were obtained in the oxidation of substrates by HRP compound I, except that the rate of reaction was much higher than in the case of HRP compound II. In addition, the rates of oxidation of phenols by compound I or II were found to be about 1000 times higher than those of anilines with similar HOMO energy levels. On the basis of these results, the mechanism of electron transfer from the substrate to the heme iron of HRP compound II is discussed.

Aniline Compounds↗

Anti-thyroglobulin autoantibodies in sera from patients with chronic thyroiditis and from healthy subjects: differences in cross-reactivity with thyroid peroxidase.

A significant portion (about 12.7%) of healthy subjects was found to contain anti-thyroglobulin (anti-Tg) antibodies in their sera. We compared the binding activities of these antibodies and of anti-Tg autoantibodies from sera of patients with chronic thyroiditis with human thyroid peroxidase (TPO). The results obtained by ELISA indicated that out of 10 healthy subjects with anti-Tg antibodies, only four had anti-Tg antibodies capable of binding to TPO, whereas anti-Tg autoantibodies from almost all patients with chronic thyroiditis possessed high binding activities to TPO. By use of the immunoprecipitation method, it was also shown that although all anti-Tg autoantibodies from patients precipitated TPO, a majority of anti-Tg antibodies from healthy subjects could not precipitate TPO. Such findings cannot be ascribed to the differences in levels of anti-Tg autoantibodies and anti-TPO autoantibodies in sera and the differences in avidities of anti-Tg antibodies in sera between healthy subjects and patients with chronic thyroiditis. Thus, it can be concluded that anti-Tg antibodies from healthy subjects differ from those of patients with chronic thyroiditis with respect to TPO binding, probably due to difference in fine specificities of these anti-Tg antibodies.

Adolescent↗

Chiari pelvic osteotomy for osteoarthritis. The influence of the torn and detached acetabular labrum.

We assessed the results of Chiari pelvic osteotomy in 64 hips with early osteoarthritis in terms of acetabular labral detachment detected pre-operatively by arthrography. At an average follow-up of four years, assessment by the Merle d'Aubigńe score showed 83% excellent or good results. These satisfactory results were achieved in only half the cases with a detached labrum, but in nearly all cases with normal or torn acetabular labra. Other factors such as the acetabular index, the level and angle of osteotomy, and the displacement following osteotomy did not affect the results. Chiari pelvic osteotomy is a worthwhile procedure for early osteoarthritis in selected cases, but a detached acetabular labrum increases the risk of clinical failure.

Acetabulum↗

Changes in serum autoantibodies to thyroid peroxidase during antithyroid drug therapy for Graves' disease.

Thyroid microsomal antigen is considered to be identical with thyroid peroxidase (TPO). Although there have been many reports concerning changes in microsomal autoantibody during the course of antithyroid drug therapy for Graves' disease, little is known about this matter in relation to TPO autoantibody (TPOab). Therefore, in this paper, we studied serial changes in the latter autoantibody. Initial levels of serum TPOab (% immunoprecipitation) in 13 patients with hyperthyroid Graves' disease ranged from -11.3% to +84.5% (mean +/- SD, 38.9 +/- 31.8%). Of three patients with persistently increased serum TPOab throughout drug therapy, all had recurrence of hyperthyroidism after the drug was discontinued. Of seven patients whose TPOab levels were initially high but subsequently decreased, four had remission of the disease after drug therapy. Inhibition by TPOab of the TPO activity was also demonstrated by both guaiacol and iodide assays, and changes in this inhibitory activity during therapy varied among individuals. This inhibition was not correlated with disease remission. The decrease in serum TPOab observed in some antithyroid drug-treated patients may reflect a decline in disease activity or may be a direct effect of the drug.

Adolescent↗

[Allopurinol induced aplastic anemia in a patient with chronic renal failure].

A 43 year old female patient with chronic renal failure originated from polycystic kidney disease was admitted with pancytopenia. Prior to the admission, she had a history of taking allopurinol for 3 months. Allopurinol was discontinued immediately and she was treated with blood transfusion (platelet and RBC) and fluoxymesterone. The lymphocyte stimulation tests were negative for allopurinol and oxipurinol. The determination of serum levels of allopurinol and oxipurinol was disclosed to be not so high compared with other patients treated with allopurinol. On 45th day after admission, she was transfused with bone marrow from her elder brother. Thereafter bone marrow finding of the patient began to improve despite the lack of bone marrow engraftment. For further improvement, pulse treatment with corticosteroid was carried out. Although the pathophysiology of allopurinol-induced aplastic anemia remains unknown, it is interesting to note that bone marrow transfusion and pulse treatment with corticosteroid seemed effective in this case.

Adult↗

Improved assay method for activity of thyroid peroxidase-catalysed coupling of iodotyrosine residues of thyroglobulin utilizing h.p.l.c. for analysis of iodothyronines.

The coupling of iodotyrosine residues of thyroglobulin (Tg) catalysed by thyroid peroxidase (TPO) has scarcely been studied with respect to the TPO of abnormal human thyroid glands. The present paper proposes a rapid and convenient assay method applicable for determining the coupling activity of a sample of less than 500 mg from each patient's thyroid. The main characteristics of the method are as follows: (i) mitochondrial/microsomal fractions of thyroid glands were treated with sodium cholate plus trypsin, and the supernatants obtained by ultracentrifugation were directly used for the assay of coupling and peroxidase activity of TPO; (ii) the formation of iodotyrosine residues catalysed by TPO was performed by using chemically iodinated Graves'-disease Tg containing 41 iodine atoms per molecule and with a high iodotyrosine and a low iodothyronine content; (iii) newly synthesized iodothyronine residues (thyroxine, 3,5,3'-tri-iodothyronine, and 3,3',5'-tri-iodothyronine) were analysed by h.p.l.c. after hydrolysis of Tg with proteinases and extraction of iodothyronines with ethyl acetate.

Chromatography, High Pressure Liquid↗

Interaction of aromatic donor molecules with lactoperoxidase probed by optical difference spectra.

On the basis of optical difference spectra, lactoperoxidase (LPO) was shown to form a 1:1 complex with aromatic donor molecules: resorcinol, hydroquinone, phenol, p-cresol, guaiacol, aniline, and benzohydroxamic acid. As compared with horseradish peroxidase (HRP), the values of the dissociation constant, Kd, of LPO-donor complexes were found to be 4-720-fold larger and were not greatly changed in the presence of KCN and by changes in pH in the range 4-9. The apparent enthalpy and entropy of the binding reactions were found to be -13 kJ mol-1 and -29 J mol-1 K-1, respectively, somewhat smaller (in absolute value) than the corresponding values of HRP. The difference spectra of LPO-donor complexes resembled each other, in contrast to the case of HRP, and the bindings of the donors to LPO occurred in a competitive fashion between the donors. Incubation of LPO with phenylhydrazine and hydrogen peroxide markedly depressed donor binding, the intensity of the Soret band, and the catalytic activity, probably as the result of formation of meso-phenyl derivatives of the heme. These findings suggest that the binding of aromatic donors to LPO occurs at a specific site, probably near the heme edge, where the electron transfer in the peroxidase reaction may take place.

Animals↗