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Biomedical subjects

J Yamakawa

Publications and source records attributed to J Yamakawa.

16 recordsLinked to original sources
PubMed1995

Time course of vestibular function in patients with menière's disease following vestibular nerve section.

Harmonic acceleration rotational test and vestibular autorotation test (VAT) were performed on 8 patients with Menière's disease before and after vestibular nerve section. Sinusoidal rotations of 0.01-0.64 Hz were used in the HA rotational test. VAT was performed at frequencies between 0.5 and 6 Hz. Two weeks after operation, almost all the patients consistently showed response asymmetry toward the healthy ear at all stimulus frequencies and a reduction in sensitivity to rotational stimuli at 0.01 Hz in the HA rotational test. Prior to surgery, the time constant of the vestibulo-ocular reflex (VOR) varied according to the residual vestibular function of each patient. The time constant then dropped to a mean of 4.2 s after the operation. In the VAT, almost all the patients showed a gain reduction at all frequency ranges on the seventh postoperative day. These findings suggest that response asymmetry and gain at 0.01 Hz in the HA rotational test are valuable for evaluating the time course of the compensation of the vestibular function after surgery and that the VOR time constant is useful in detecting whether the vestibular nerve has been sectioned correctly.

Adult↗
PubMed1994

Humanization of mouse anti-human IL-2 receptor antibody B-B10.

Mouse monoclonal anti-human IL-2 receptor antibody (B-B10) inhibits IL-2-dependent human T-cell proliferation. It has been used in clinical trials in the transplantation field and promising results are being accumulated. Mouse B-B10 antibody was humanized by grafting all CDRs and some framework amino acid residues onto human antibodies, KAS for VH and PAY for V kappa. Nine humanized B-B10s with differently grafted framework residues were constructed and assessed for their biological activities. One of these humanized B-B10, M5, showed nearly the same activity as the mouse B-B10. The 49th residue of V kappa was demonstrated to play a crucial role in the antigen-antibody interaction by 3-D structure analysis with a computer modeling system.

Amino Acid Sequence↗
PubMed1994

Comparison of assay procedures for solubilized thyroid hormone receptor.

Seven procedures for the assay of thyroid hormone receptor were compared. Receptors from rat liver nuclei were incubated with [125I] triiodothyronine (T3), and the hormone bound to the receptors was separated by the different methods and its radioactivity was counted. Column chromatography on Sephadex G-25, filtration on nitrocellulose membranes, glass filters, or diethylaminoethyl cellulose disks, and vortex/centrifugation with use of hydroxyapatite, Dowex AG 1 x 8 resin, or a mixture of charcoal and dextran were used. Filtration on a nitrocellulose membrane was the most sensitive and accurate method. The use of Dowex AG 1 x 8 was the easiest. Filtration on a glass filter was the best when samples were particulate.

Animals↗
PubMed1993

Investigation of antigenic determinants in thyroid peroxidase by synthesis of possible sequential peptides.

One way to locate antigenic determinants in thyroid peroxidase (TPO) is to evaluate the binding of chemically synthesized peptides to autoantibodies. A major epitope of TPO involved in thyroid autoimmunity has been reported to be at residues 590 to 675. Therefore, we synthesized three peptides (P1, residues 603-610; P2, 615-630; and P3, 654-665) in the most antigenic part of this range, as judged by antigenicity analysis, and measured their antigenicity by enzyme-linked immunosorbent assay (ELISA). Amino groups protected with fluorenyl-methoxycarbonyl were used in the synthesis. Sera from 42 untreated patients with Hashimoto's disease and 30 untreated patients with Graves' disease were tested for binding with each peptide. In addition, 6 sera with antibodies against denatured and reduced microsomal antigen were tested. Sera obtained from 22 normal subjects were used as a control. Binding of sera from the patients with autoimmune thyroid disease to the synthetic peptides was weak, about 1% of binding to thyroid microsomes prepared from Graves' thyroid. However, the ELISA index of a mixture of P1, P2, and P3 was significantly higher in the patients with Hashimoto's disease than in the healthy subjects. For both P2 and P3, the ELISA index of the sera with antibodies against denatured and reduced TPO was higher than that of the sera from normal subjects. These results suggested 1) that the antigenic epitopes of TPO recognized by autoantibodies may be conformational and discontinuous, and 2) that antibodies against these linear portions of TPO may exist in patients with Hashimoto's disease.

Autoantibodies↗
PubMed1992

[A case report of adenoid cystic carcinoma of the nasal septum].

A 50-year-old woman with adenoid cystic carcinoma of the nasal septum is presented. Her chief complaint was recurrent epistaxis. Surgery was originally performed to remove a nasal polyp, but during resection, the surgeon discovered that the mass had arisen from the nasal septum, so only a biopsy was done. The pathological report was adenoid cystic carcinoma, so she was referred and admitted to our hospital. A flat 1.5 x 1.5 cm tumor was recognized on the left side of the nasal septum. Nasal septectomy was performed. The tumor was dissected with nasal septal cartilage, and the defect was covered with a free skin flap from the thigh. The incidence of malignant tumors from the nasal septum is very low, composing from 2.7% to 8.4% of nasal and paranasal malignant tumors. Therefore the incidence of adenoid cystic carcinoma in particular is very low.

Carcinoma, Adenoid Cystic↗
PubMed1991

Thyroid microsomal antigen in Graves' thyroid is not different from that in normal thyroid.

Differences from normal in microsomal antigen (M-Ag) may be involved in the development of autoimmune thyroid disease. We compared the M-Ag in Graves' thyroid immunologically and biochemically to that in normal thyroid. The concentration of M-Ag, measured with an enzyme-linked immunosorbent assay, was significantly greater in the Graves' microsomes than in normal microsomes. Binding of a patient's microsomal antibody to Graves' microsomes was completely inhibited when the serum was first incubated with normal thyroid microsomes. Sodium dodecylsulfate-polyacrylamide gel electrophoresis and Western blotting were done with a monoclonal antibody to denatured M-Ag. In both Graves' and normal thyroids, M-Ag existed as 107-, 101-, and 95-kDa peptides. After incubation with V8 protease, the residual antigenic peptide had a molecular weight of less than 60,000 and after incubation with trypsin, 95- and 87-kDa peptides and several smaller antigenic peptides were found. There were no significant differences in the pattern of normal and Graves' microsomes after digestion. Two-dimensional gel electrophoresis of Graves' microsomes showed that the isoelectric point for the 107-kDa peptide was at pH 7.2; that for the 101-kDa peptide was at pH 6.2, and that for the 95-kDa peptide was at 6.5. These values were not different from those observed for normal microsomes. These results indicate that M-Ag in Graves' thyroid does not differ from that in normal thyroid, and that microsomal antibodies in autoimmune thyroid disease probably do no arise from differences in the antigen.

Autoantigens↗
PubMed1991

Why no simple relationship between thyroid peroxidase activity-inhibiting immunoglobulins and thyroid function in autoimmune thyroid disease?

We have reported that some anti-thyroid peroxidase antibodies inhibit the activity of thyroid peroxidase in vitro. These thyroid peroxidase activity-inhibiting immunoglobulins seem to inhibit thyroid function in some patients, but the relationship between thyroid peroxidase activity-inhibiting immunoglobulins and thyroid function is not simple. We designed this study to explore this lack of a simple relationship. We stained immunoglobulin G deposits by immunofluorescence staining or the peroxidase-antiperoxidase method, and stained endogenous thyroid peroxidase activity by enzyme histochemistry in thyroid sections. When cryostat thyroid sections were incubated with thyroid peroxidase activity-inhibiting immunoglobulins, immunoglobulin G deposits were seen as lines of stain on the apical border and as intracellular staining, and endogenous thyroid peroxidase activity was inhibited. In paraffin-embedded thyroid sections from 5 Hashimoto's patients and 6 Graves' patients, immunoglobulin G deposits were not found on the apical border of the follicular epithelium. In frozen thyroid sections from 22 Graves' patients, no clear deposits of immunoglobulin G on this apical border were seen. In organ-cultured thyroid slices incubated with thyroid peroxidase activity-inhibiting immunoglobulins, endogenous thyroid peroxidase activity was not inhibited. In conclusion, thyroid peroxidase activity-inhibiting immunoglobulins may reach its antigen only with difficulty. This is one of the reasons why no simple relationship is observed between thyroid peroxidase activity-inhibiting immunoglobulins and thyroid function.

Antigens↗
PubMed1987

Myasthenia gravis associated with Graves' disease in Japan.

The prevalence of myasthenia gravis in Graves' disease was 0.14% in the 22,956 patients with Graves' disease who came during 1968-1979 to the Ito Hospital, Tokyo. While age at the onset of Graves' disease in patients with myasthenia gravis was slightly lower than that in those with Graves' disease without myasthenia gravis, age at the onset of myasthenia gravis in patients with Graves' disease was not different from that of myasthenia gravis patients without Graves' disease. Of 33 patients with both myasthenia gravis and Graves' disease, 8 developed myasthenia gravis first, 13 developed Graves' disease first, and in 12 the two diseases occurred concurrently. Most patients in whom Graves' disease developed first had clinical manifestations of myasthenia gravis within 2 years of the onset of Graves' disease. The dosage of an anticholinergic drug required to control symptoms decreased as the thyroid function was normalized, and no cases showed the "see-saw phenomenon".

Adolescent↗
PubMed1984

Occurrence of protein kinases NI and NII in human and porcine thyroids.

Cyclic nucleotide-independent protein kinases that preferentially phosphorylated casein and phosvitin as substrate were detected in the nuclei of human and porcine thyroid tissues, and compared with those from rat liver. Enzymes were extracted from the isolated nuclei with a buffer solution containing 0.4 M NaCl, and analyzed by DEAE-Sephadex and phosphocellulose column chromatographies. The chromatographies, together with the characterization of the enzymes, demonstrated that human and porcine thyroid tissues contained two major casein kinases in the cell nuclei, the properties of which revealed that they are to be identified as protein kinases NI and NII.

Animals↗
PubMed1984

Is it necessary to adjust the replacement dose of thyroid hormone to the season in patients with hypothyroidism?

Hypothalamo-pituitary-thyroid activity varies with the temperature of the environment; we therefore measured variables involved with thyroid function in summer and winter in normal controls and in patients with primary hypothyroidism. All seven patients had impalpable thyroid glands and had received a set replacement dose of thyroxine for over a year. In the patients, serum T3 and FT4 levels were slightly but significantly lower in winter, and TSH levels and delta TSH at 30 minutes in the TRH tests were significantly higher. In the controls, there were no significant differences between summer and winter in these values. These findings suggest that the dose required for replacement of thyroid hormone in patients with hypothyroidism may be higher in winter than in summer.

Adult↗
PubMed1984

Serum and tissue coenzyme Q9 in rats with thyroid dysfunctions.

Serum and tissue CoQ9 levels were determined in hypothyroid, euthyroid and hyperthyroid rats. A significant negative correlation was demonstrated between serum FT4 or T3 and CoQ9 in rats with various states of thyroid functions. Liver CoQ9 was significantly increased in rats rendered mildly hyperthyroid. There was a significant positive correlation between serum FT4 or T3 and liver CoQ9. While liver CoQ9 did not significantly change in severely hyperthyroid animals, liver mitochondrial CoQ9 showed a significant positive correlation with serum T3. Kidney and heart CoQ9 levels did not significantly change in hyperthyroid rats, but those in hypothyroid rats showed a tendency to increase. It was suggested that the synthesis of CoQ9 was increased in the liver in hyperthyroidism.

Animals↗
PubMed1984

Increased micrococcal nuclease sensitivity and/or solubility in nuclei from Graves' disease thyroid tissue.

The sensitivity of nuclei to micrococcal nuclease was compared in thyroid tissue obtained from euthyroid patients with solitary cold nodules and from patients with Graves' disease. A significant increase in the solubility and/or the sensitivity of nuclei to the nuclease was found in thyroid tissue from patients with Graves' disease. Electrophoretic analysis of DNA in chromatin solubilized by the nuclease revealed that the amount of oligonucleosomal DNA was increased, and that of polynucleosomal DNA was even more increased, in nuclei from Graves' thyroids than in those from normal thyroids. Polyacrylamide gel electrophoretic analysis in Triton acid-urea showed that the extent of histone acetylation in nuclei from Graves' thyroids was almost the same as in those from normal thyroids. These findings suggest that the state of chromatin organization in Graves' thyroid nuclei is different from that in normal thyroid nuclei and is independent of the extent of histone acetylation.

Acetylation↗
PubMed1984

Tissue calmodulin levels in normal and Graves' thyroids.

Calmodulin levels in normal human thyroids and Graves' disease thyroids were measured by specific radioimmunoassay in the presence of ethyleneglycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). The calmodulin levels in tissues from patients with Graves' disease treated with thionamide drugs were significantly higher than those in normal tissues from euthyroid patients with solitary cold nodules (normal: 484 +/- 50 ng/mg protein, mean +/- SE, n = 15; Graves': 901 +/- 54 ng/mg protein, n = 48, p less than 0.001). Such a rise in calmodulin levels in Graves' disease thyroids was also present even after the administration of 50 micrograms of T3 for 5 days before operation (828 +/- 137 ng/mg protein, n = 6, p less than 0.01). Calmodulin levels in Graves' disease thyroids were closely related to the cell height of follicular epithelium. Calmodulin levels in a columnar cell predominant group were significantly higher than those in a flat cell predominant or a cuboidal cell predominant group (columnar cell predominant: 1150 +/- 118 ng/mg protein, n = 13; flat cell predominant: 561 +/- 125 ng/mg protein, n = 3, p less than 0.05; cuboidal cell predominant: 596 +/- 40 ng/mg protein, n = 25, p less than 0.001). The increase in calmodulin content in Graves' disease thyroid could therefore possibly be attributed to the stimulation of the thyroid gland by the thyroid stimulating antibody. An immunofluorescence study demonstrated the presence of calmodulin immunoreactivity in the thyroid epithelial cells, particularly enriched in the apical border in the form of a granulated structure.

Calmodulin↗
PubMed1983

Filter-binding assay procedure for thyroid hormone receptors.

An assay procedure for thyroid hormone receptor activity which used nitrocellulose membrane filters was developed. Receptor proteins, extracted from washed rat liver nuclei with a 0.4 M NaCl solution, were incubated with 125I-labeled thyroid hormone (T3), and filtered on the cellulose ester membranes under suction at 2 degrees C. The filters were subsequently washed with cold buffer and counted for 125I radioactivity. The method allowed an accurate estimation of the receptor activity, satisfying a linear relationship between the activity and the receptor protein concentrations. The usefulness of this filter-binding method became evident when it was compared with the conventional procedure that employs Sephadex G-25 columns. For practical application to routine assays, various filtration conditions were examined, and a standard procedure was established. Using this technique, the isolated receptors were determined to possess an apparent Kd of 1.38 X 10(-10) M and a pH optimum of T3 binding at 8.2-8.4.

Animals↗
PubMed1982

A case report on disequilibrium hypercalcemia in hyperthyroidism. Comparison of calcium metabolism with other patients with hyperthyroidism.

The patient, a 30-year-old woman, was admitted to Itoh Hospital in February, 1979 for hyperthyroidism. She had a history of pyelonephritis and recurrent urinary tract infection. Laboratory data on admission revealed overt hyperthyroidism (T3: 405 ng/dl, T4: 22.5 micrograms/dl and T3U: 57.--%), severe hypercalcemia of 12.6 mg/dl and hypercalciuria. The PSP excretion and GFR were both decreased. Serum c-PTH was nondetectable. As the thyroid function improved, there was a gradual decrease and later normalization of plasma calcium, phosphate and urinary calcium excretion. When subtotal thyroidectomy was performed on October 19, 1979, hypertrophy of the parathyroid gland was not demonstrated. In comparison with 98 other hyperthyroid patients, the pathogenesis of hypercalcemia was discussed. In conclusion, hypercalcemia in the patient, T. Y., was regarded as a kind of disequilibrium hypercalcemia which resulted from a combination of increased bone turnover and decreased calcium excretion by the kidney.

Adult↗