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Biomedical subjects

T Hachiya

Publications and source records attributed to T Hachiya.

At least 181 records · Page 10Linked to original sources

Inhibition of TSH binding to chicken thyroid by some cases of LATS (long acting thyroid stimulator).

TSH receptor antibody (TRAb) activity using chicken thyroid receptor (c-TRAb) and porcine thyroid receptor (p-TRAb) was determined by the incubation of 125I-bovine TSH with each receptor. Both c-TRAb and p-TRAb activity in LATS positive and negative Graves' sera were compared. 15 out of 39 LATS positive sera and 4 out of 46 LATS negative sera had positive c-TRAb activity. On the other hand, all LATS positive sera and 33 out of 46 LATS negative sera had positive p-TRAb activity. No relationship between c-TRAb and p-TRAb activity was observed, and there was also no correlation between c-TRAb and LATS activity. Changes in c-TRAb, p-TRAb and LATS activity in the clinical course of patients with Graves' disease were examined. These activities were parallel in some cases, but in others they were not. A weak c-TRAb activity was observed in 4 out of 29 Hashimoto's disease, but all cases with thyroid cancer and subacute thyroiditis showed no activity. Sera with positive c-TRAb activity did not stimulate chicken thyroid in chick bioassay. These results suggest that some cases of TRAb in Graves' disease (mainly LATS) inhibit TSH binding to chicken thyroid receptor (non-mammalian species) in the same way as mammalian thyroid, but may not have any stimulatory action on thyroid hormone synthesis. It is interesting to note that TRAb including LATS have the similar effect on TSH receptor even in nonmammalian species.

Animals↗

Increased ferritin levels in the fluid of thyroid cyst.

High ferritin levels in the aspirate of thyroid cyst (Six yellow clear, 4 yellow turbid and 10 chocolate colored turbid) without apparent sings of malignancy were found. The mean concentration in the 3,000 X g supernatant of the fluid was 40,116 ng/ml, and the 3,000 X g precipitate was 11,147 ng/ml. All cases showed normal levels of serum ferritin. Con A binding with ferritin was distributed from low to high. These ferritins showed a molecular weight of approximately 450,000 which was the same as found in human spleen and liver. The continuous increase in ferritin levels in thyroid cyst fluid was found by a chronological study in some cases. When tumor markers such as CEA, NCA, CA 19-9 and alpha 1-acid glycoprotein (alpha 1-AG, acute phase reactant) were examined simultaneously, an increase in some of the cyst fluid was observed. However, the incidence and the rate of increase of these tumor markers and acute phase reactant were low compared to ferritin. Neither a correlation between ferritin and CEA, nor between ferritin and CA 19-9 was found. The increase in ferritin in thyroid cyst fluids may be due to the increased synthesis, release and storage by the inflammatory cells.

Antigens, Neoplasm↗

The influence of body size on the ventilatory response to hypercapnia.

The slope of ventilatory response to hypercapnia at rest was determined in 77 healthy male students by means of the CO2 rebreathing method. It was found that the hypercapnic ventilatory response slope (S) was significantly lower in the lean group with BMI (body mass index) below 19 than that in the normal group, while there were no significant correlation between S and body weight or height. These results indicate that sensitivity of hypercapnia in the lean subjects differed from that of normal and overweight subjects.

Adolescent↗

Comparison of LATS activity and TSH receptor antibody in Graves' disease.

TSH-receptor antibody (TRAb) activity and LATS activity of Graves' sera were compared. All of 50 LATS-positive cases were TRAb positive, although only 63% of LATS-negative cases were TRAb positive. Binding of 125I-TSH to the TSH receptors was inhibited dose-dependently by LATS-immunoglobulin. However, no correlation between TRAb activity and LATS activity was observed. TRAb was positive in 2 LATS-positive cases even when the symptoms of hyperthyroidism were controlled by treatment (antithyroid or radioisotope). The positive TRAb was not changed in 4 Graves' disease patients whose LATS activity had disappeared following antithyroid treatment. These clinical studies show that TRAb is more sensitive than LATS and suggest that LATS may be one of a heterogenous population of antibodies to the TSH receptor in Graves' disease.

Autoantibodies↗

Characteristics of auto-antibodies to bovine TSH in the serum of two patients with Graves' disease.

In this report we describe the characteristics of auto-antibodies to bovine TSH (bTSH) detected in the serum of 2 females among 102 patients with Graves' disease. These patients had never been injected with bTSH. One patient had high LATS activity and high bTSH binding activity after isotope therapy. The other patient showed no detectable LATS activity. Interestingly, the antibody showed a specifically high binding activity for the labelled TSH preparation purified by receptor. The auto-antibody could be demonstrated by the double antibody method, polyethylene glycol method, and by gel-filtration. The antibody was polyclonal immunoglobulin G (IgG). Because the binding of [125I]bTSH with the patient's antibody was inhibited by pituitary extracts from mammalian species other than human, this antibody may cross-react with bovine, rat, dog, rabbit and whale TSH. Although the incidence of the antibody in Graves' disease is low and the pathological significance remains obscure, the existence of this antibody in the serum of patients may suggest that autoimmune mechanisms may involve not only the thyroid but also the pituitary in Graves' disease.

Adult↗

Protection of the ischemic myocardium with calcium antagonistic drugs.

Ligation of the coronary artery to produce myocardial infarction experimentally was performed in 41 mongrel dogs. The dogs were then treated with niludipine or nifedipine. Niludipine in doses of 0.05 mg/kg/day (niludipine A group) and 0.1 mg/kg/day (niludipine B group) or nifedipine 0.05 mg/kg/day (nifedipine group) was administered for 7 postoperative days. The animals were sacrificed, their hearts removed and extent of myocardial damage studied. 1. The size of infarctions measured by 99mTc-PYP myocardial scintigrams of the isolated heart was significantly smaller in the niludipine A group. 2. The degree of ischemia indicated by LDH isoenzyme patterns was lowest in the niludipine A group followed by nifedipine and niludipine B group in this order. The value for H subunits of LDH isoenzymes on the subepicardial side was higher in the nifedipine group. 3. Histopathological findings varied from specimen to specimen, but in general the niludipine A group showed best improvement. Our results suggest that the calcium antagonistic drugs, niludipine and nifedipine, seem to have myocardium protective properties in dogs. To what degree these findings can be applied clinically needs further studies.

Angiocardiography↗

Purification of carcinoembryonic antigen by affinity chromatography with anti-alpha 1-acid glycoprotein.

Purification of radiolabeled carcinoembryonic antigen (CEA) preparations by affinity chromatography with anti-AG bound to Sepharose was attempted, since an immunological similarity between AG (alpha 1-acid glycoprotein) and a portion of CEA had been noted. When 125I-CEA was purified in this manner, the fraction which did not bind to the column showed decreased reactivity with either anti-AG or anti-CEA. The retained fraction showed enhanced reactivity with both anti-AG and anti-CEA. The yield of purified CEA increased when the CEA preparation was allowed to react with the anti-AG column overnight. Purification of CEA from tumor tissue was performed by affinity chromatography. A perchloric acid (PCA) extract from cancer tissue was mixed with antiserum against CEA to give an immune complex, and a CEA-reactive fraction obtained by PCA extraction. The CEA-reactive fraction was eluted from a Sephadex G-200 column, and final purification was by anti-AG chromatography. When purified CEA was applied to a Sephadex G-200 column with carrier protein after labeling with 125I, the eluted radioactivity was found only in the 180,000 dalton fraction. Almost all the radioactivity was precipitated from the labeled protein by either anti-AG or anti-CEA. Purification of CEA is possible by affinity chromatography with anti-AG bound to Sepharose.

Animals↗

Immunological similarity of CEA with alpha 1-acid glycoprotein (orosomucoid).

We have demonstrated that 125 I-CEA (carcinoembryonic antigen) from two commercial sources (Roche and CIS RIA kit) can be precipitated by antibody to alpha 1-acid glycoprotein (AG) dose-dependently. The binding of 125 I-CEA to anti-AG can be displaced by unlabelled AG, though, there was no cross-reaction between AG and anti-CEA. The data strongly suggest that CEA has an immunological similarity to AG. The perchloric acid extract from cancerous tissue was fractionated on a Sephadex G-200 column, and the first eluted fraction (containing large amounts of CEA) was subjected to affinity chromatography using anti-AG bound to Sepharose. The bound fraction was eluted, labelled with 125 I, and then applied to a Sephadex G-200 column with carrier protein. The radioactivity was found mainly in the large molecular size eluted fraction (Fr 1). Almost all radioactivity of Fr 1 was precipitated by anti-AG and anti-CEA. This experiment also demonstrated that a large molecular weight component (Mr: 180 000) obtained from tumor was immunologically related to both CEA and AG. Based on differences in binding affinities between CEA with anti-CEA and with anti-AG we postulate that CEA may be a large molecular precursor of AG (big form of AG).

Carcinoembryonic Antigen↗

Immunological similarity of NCA (non-specific cross-reacting antigen) in feces with alpha 1-acid glycoprotein.

We have recently suggested that carcinoembryonic antigen (CEA) may contain alpha 1-acid glycoprotein (AG) antigenic determinant. In the present work we examined a protein with CEA-like activity in the feces of healthy subjects (NCA) for immunological cross-reactivity with AG. When the perchloric acid extract of feces was fractionated on a Sephadex G-200, two fractions (large and small molecular weight) were obtained. The large molecular weight fraction had higher CEA activity than the small one. The perchloric acid (PCA) extract of feces was subjected to affinity chromatography using anti-CEA bound to Sepharose, and the bound protein was labelled with 125I, and then fractionated on a Sephadex G-200 column. Two radioactive peaks, Peak 1 corresponding to an approximate Mr of 180 000 and Peak 2, corresponding to an approximate Mr of 60 000 were found. Both peaks showed immunoreactivity with either anti-CEA or anti-AG. This experiment suggests the presence of two kinds of CEA-reactive proteins in feces: one which may be a big protein with immunological similarity to AG and a second which appears to be a hydrolysed fragment of this protein.

Antigens↗

An assay for antibodies to thyroid plasma membrane using the isotope-labeled protein A.

An assay for detection of serum IgG binding to thyroid membrane using 125I-Protein A was examined. The test serum is incubated with purified thyroid membranes, and the IgG bound to the membrane is detected by its interaction with 125I-Protein A. Most of the bound IgG is not bound to the TSH receptor, because TSH does not induce any appreciable decrease in the binding of the IgG to thyroid membranes. Increased serum IgG binding to thyroid membrane is found in most patients with Graves' disease and Hashimoto's thyroiditis, but not in patients with thyroid cancer or simple goiter. Many sera with positive binding activity showed positive microsomal antibody. Serum IgG binding to thyroid membrane in Graves' disease correlates neither with LATS activity nor thyroglobulin antibody. This finding suggests that TSH receptor is not involved in the reaction. The assay method is useful for measuring the binding immunoglobulin for thyroid membrane that is frequently increased in autoimmune thyroid disease, and the present data provide further support to the concept that thyroid autoimmune disorders are associated with antibodies to thyroid cell surface components.

Cell Membrane↗