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Biomedical subjects

Y Iida

Publications and source records attributed to Y Iida.

At least 145 records · Page 8Linked to original sources

Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria is an acquired hematopoietic disease characterized by abnormal blood cell populations in which the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor is deficient. Deficiency of surface expressions of GPI-anchored complement inhibitors leads to complement-mediated hemolysis. Here we report that PIG-A, which participates in the early step of GPI anchor biosynthesis, is the gene responsible for paroxysmal nocturnal hemoglobinuria. Affected granulocytes and B lymphocytes had the same somatic mutation of PIG-A, indicating their clonal origin from a multipotential hematopoietic stem cell. We localized PIG-A to the X chromosome, which accounts for expression of the recessive phenotype of the somatic mutation and the fact that the same one of the multiple biosynthetic steps is affected in all patients so far characterized.

B-Lymphocytes↗

The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis.

The glycosylphosphatidylinositol (GPI) anchor is a membrane attachment structure of many proteins and occurs in a wide variety of eukaryotes from yeasts to mammals. The structure of the core of the GPI anchor is conserved in protozoa and mammals and so is its biosynthetic pathway. A complementary DNA encoding a human protein termed PIG-A (phosphatidylinositol glycan-class A) was cloned. PIG-A was necessary for synthesis of N-acetylglucosaminyl-phosphatidylinositol, the very early intermediate in GPI-anchor biosynthesis.

Amino Acid Sequence↗

Local cerebral glucose utilization in the interictal state of the spontaneously epileptic rat (SER).

Local cerebral glucose utilization (LCGU) in spontaneously epileptic rats (SER) and in their parent strains, zitter (ZI) and Kyoto-Wistar (KW) rats was studied by autoradiography with [14C]2-deoxyglucose. Compared to the LCGU in age-matched KW rats, LCGU in 8-week-old SERs, which had not yet exhibited epileptic seizures, was low in all brain regions examined, and there were no significant differences among the regions. Moreover, there were no differences in LCGU among all regions examined in both SERs and in ZI rats. By contrast, the interictal LCGU in 13-week-old SERs, which did exhibit epileptic seizures, was generally lower than in the other two strains, particularly in the hippocampus and amygdala. These findings suggest that the epileptogenic focus in SERs may lie in the hippocampus and amygdala.

Animals↗

Myocardial accumulation of a dopamine D2 receptor-binding radioligand, 2'-iodospiperone.

125I-2'-iodospiperone (2'-ISP), which has a high and selective affinity for dopamine D2 receptors, produced a high myocardial accumulation of radioactivity in the early phase after intravenous injection into mice. A human scintigraphic study also showed that the myocardium was clearly visualized soon after intravenous injection of the tracer. Analysis of the myocardial homogenate obtained from mice showed that 125I-2'-ISP was metabolically stable and was taken up the myocardium in its intact form. Administration of spiperone significantly reduced the myocardial uptake of 125I-2'-ISP in mice. Treatment with haloperidol and (+) butaclamol, which have a high affinity for dopamine D2 receptors, also tended to reduce the myocardial uptake of radioactivity, while (-)-butaclamol, which has no affinity for dopamine D2 receptors, caused no change in uptake. These findings suggest that the myocardial accumulation of 2'-ISP occurred in association with dopamine D2 (DA2) receptors.

Animals↗

Contact sensitivity and cross-reactivity of budesonide.

5 cases of allergic contact dermatitis due to budesonide are described. We studied the antigen determinant structures in these cases by applying patch tests with several substances related to budesonide. 2 cases showed cross-reactions to both amcinonide and prednisolone acetate. The antigen determinant structure is also discussed.

Adult↗

beta 2-Microglobulin modified with advanced glycation end products is a major component of hemodialysis-associated amyloidosis.

beta 2-Microglobulin (beta 2M) is a major constituent of amyloid fibrils in hemodialysis-associated amyloidosis, a complication of long-term hemodialysis patients. Amyloid fibril proteins were isolated from connective tissues forming carpal tunnels in hemodialysis patients with carpal tunnel syndrome. Two-dimensional polyacrylamide gel electrophoresis and Western blotting demonstrated that most of the beta 2M forming amyloid fibrils exhibited a more acidic pI value than normal beta 2M. This acidic beta 2M was also found in a small fraction of beta 2M in sera and urine from these patients, whereas heterogeneity was not observed in healthy individuals. We purified acidic and normal beta 2M from the urine of long-term hemodialysis patients and compared their physicochemical and immunochemical properties. Acidic beta 2M, but not normal beta 2M, was brown in color and fluoresced, both of which are characteristics of advanced glycation end products (AGEs) of the Maillard reaction. Immunochemical studies showed that acidic beta 2M reacted with anti-AGE antibody and also with an antibody against an Amadori product, an early product of the Maillard reaction, but normal beta 2M did not react with either antibody. Incubating normal beta 2M with glucose in vitro resulted in a shift to a more acidic pI, generation of fluorescence, and immunoreactivity to the anti-AGE antibody. The beta 2M forming amyloid fibrils also reacted with anti-AGE antibody. These data provided evidence that AGE-modified beta 2M is a dominant constituent of the amyloid deposits in hemodialysis-associated amyloidosis.

Amyloidosis↗

Thyrotropin receptor antibodies in hypothyroid Graves' disease.

To clarify the relation of TSH receptor antibody (TRAb) to Graves' ophthalmopathy and thyroid function, the activities of TSH binding inhibitor immunoglobulins, thyroid-stimulating antibodies, and thyroid stimulation-blocking antibodies were measured in five patients with hypothyroid Graves' disease. The diagnosis was based on the presence of Graves' ophthalmopathy and either permanent or transient hypothyroidism without a history of treatment for hyperthyroid Graves' disease. TSH binding inhibitor immunoglobulins and thyroid-stimulating antibodies were detected in all five patients. Thyroid stimulation-blocking antibodies results indicated that a blocking type of TRAb was not a cause of hypothyroidism. Destructive changes in the thyroid were probably responsible for hypothyroidism, since 1) high antibody titers against thyroglobulin and thyroid microsomal antigen, 2) diffuse hypoechogenicity of the thyroid on ultrasonography, 3) absent or impaired responses of serum T3 after TRH or TSH stimulation, and 4) histological findings similar to those in Hashimoto's thyroiditis were observed. In all patients except one, thyroid function was changeable, with euthyroid and even subclinical hyperthyroid episodes occurring during the course of the illness. It is conceivable that such unstable thyroid function may be attributable to subtle changes in the balance between the effects of destructive changes in the thyroid and the stimulatory effects of TRAb. In conclusion, all patients had TRAb, suggesting a possible relationship between such antibodies and Graves' ophthalmopathy. Patients develop euthyroidism or subclinical hyperthyroidism during the course of the illness with high frequency.

Adult↗

An approach for assaying benzodiazepine receptor binding with radioiodinated ligand: 125I-labeled diazepam derivative.

[125I]2'-Iododiazepam (IDZ) was prepared and its application in a benzodiazepine receptor binding assay was studied. [125I]2'-IDZ binds to the rat cortical membrane with a high affinity (Kd, 0.66 nM). Various benzodiazepines showed competition with [125I]2'-IDZ for the binding sites in the rat cortical membrane, and the specificity of its binding correlated well with that of [3H]diazepam (r = 0.992, p < 0.001). These findings suggested that [125I]2'-IDZ binds to the same sites as [3H]diazepam and indicated that [125I]2'-IDZ can be used in a benzodiazepine receptor assay.

Animals↗

Synthesis and evaluation of (piperidinomethylene)bis(phosphonic acid) derivatives as anti-osteoporosis agents.

Some (piperidinomethylene)bis(phosphonic acid) derivatives were prepared and their activity to inhibit a rise in serum calcium induced by parathyroid hormone in thyroparathyroidectomised rats was evaluated. Several (4-alkylidene-, 4,4-dialkyl-, or 4-alkyl-4-halopiperidinomethylene)bis(phosphonic acid) derivatives showed considerable inhibitory activity. But compounds having aromatic and polar substituents such as azido, hydroxy, amino and amido on the piperidine ring were generally inactive. In this study, two 4-alkylidene compounds (8a and 8b) and a 4,4-cyclic dialkyl compound (61) showed potent activity when administered either intravenously or perorally.

Animals↗

Clinical diagnostic potentials of thyroid ultrasonography and scintigraphy: an evaluation.

This prospective study was designed to evaluate the potential contributions of high resolution ultrasonography (US) and Tc-99m scintigraphy in the routine diagnosis of thyroid disease. The diagnostic impacts of US and Tc-99m scintigraphy results in 177 patients visiting our thyroid clinic were assessed and scored according to the following criteria: when the information provided by either test supported, confirmed or changed the initial clinical diagnosis, they received scores of 2, 3 and 4 respectively, while score 1 was given when the test itself was useless for the differential diagnosis. US identified focal lesions that both palpation and scintigraphy had failed to detect in 14 (12.1%) of 116 patients with diffuse thyroid diseases, suggesting the necessity of routine US examinations in such patients. US scored higher than scintigraphy in the diagnosis of Hashimoto's thyroiditis, adenoma, adenocarcinoma and adenomatous goiter, and vice versa in the diagnosis of hyperthyroid and euthyroid Graves' diseases. Thus, the advantages of US over scintigraphy for morphological evaluation were confirmed. US was particularly useful for the differential diagnosis of adenomatous goiter from Hashimoto's thyroiditis or a single nodular disease. In contrast, scintigraphy gave functional images, being especially helpful for the differential diagnosis of thyrotoxicosis.

Diagnosis, Differential↗

[Bronchospasms caused by intravenous hydrocortisone sodium hemisuccinate (Solu-Cortef) in an aspirin-sensitive asthmatic patient].

This is a report of a male patient who had an anaphylaxia-like reaction to hydrocortisone sodium hemisuccinate (Solu-Cortef). A 32-year-old male with aspirin sensitivity was treated for moderate wheezing with 200 mg Solu-Cortef given intravenously. After this treatment, his condition deteriorated acutely and he was admitted to our hospital. Intradermal skin tests revealed positive immediate reactions to Solu-Cortef, Saxizon, Solu-Medrol and Predonine. Challenge tests with 100 mg Solu-Cortef and Saxizon injection showed 34% and 27% decrease, respectively in FEV1 15 min after injection. These results suggest that succinylation of steroids resulted in allergic reaction to steroids in this patient.

Adult↗

[A successful repair of tetralogy of Fallot with aortic valve regurgitation, coronary artery-pulmonary artery fistula and absent pulmonary valve in a 54-year-old man].

A 54-year-old man suffered from tetralogy of Fallot associated with aortic valve regurgitation, coronary artery-pulmonary artery fistula and absent pulmonary valve underwent intracardiac repair. The operation was completed with ligation of the fistula, aortic valve replacement using a SJM 27 A, patch closure of ventricular septal defect (perimembranous outlet type) and right ventricular outflow reconstruction using a large transannular monocusped-patch, 4 cm x 6 cm in size. Postoperative course was uneventful and he is doing well now. There was no previous reports about TOF associated with AR, the absent pulmonary valve and the coronary anomaly in the adults in the literature.

Aortic Valve Insufficiency↗

Radioiodinated 2'-iododiazepam: a potential imaging agent for SPECT investigations of benzodiazepine receptors.

2'-Iododiazepam (2'-IDZ) is the diazepam analogue iodinated at the 2'-position of C-5 phenyl ring which was synthesized and evaluated as a potential radiopharmaceutical for investigating brain benzodiazepine receptors by SPECT. The 125I-2'-iododiazepam was synthesized by halogen exchange reaction and purified by HPLC. In vitro competitive binding studies with 3H-diazepam, using rat cortical synaptosomal membranes, showed that the affinity of 2'-IDZ for benzodiazepam receptors was higher than that in diazepam and flumazenil (RO15-1788). Biodistribution studies in mice showed that the brain uptake of 2'-iododiazepam was rapid and profound, and in the brain higher accumulation was found in the cortex than in other regions. Furthermore, the cortical uptake was displaced by benzodiazepinergic compounds. In vivo uptake was assessed by autoradiographic studies. Thus, 2'-iododiazepam bound to benzodiazepine receptors in vivo and therefore holds great potential for in vivo benzodiazepine receptor studies.

Animals↗

Multiple thyroid involvement (intraglandular metastasis) in papillary thyroid carcinoma. A clinicopathologic study of 105 consecutive patients.

Multiple thyroid involvement (MTI) in papillary thyroid carcinoma was clinicopathologically studied in 105 non-selected, consecutive patients. Whole thyroids resected by total thyroidectomy were sectioned at intervals of 2-3 mm (mean number of slices per gland, 19.2) and histologically reviewed. The intraglandular cancer foci, other than the tumor regarded as the primary focus, were demonstrated in 82 (78.1%) of 105 patients. The foci were usually small (less than 4 mm) and were not accompanied by sclerotic fibrous stroma or by a fibrous capsule. These small foci were distributed around the primary lesion and also were found frequently (61.0%) in the opposite lobe as bilateral disease. In the opposite lobe, a similar incidence (approximately 30%) of disease was obtained in each of the three parts (upper, middle, and lower). The mean number of foci in patients with MTI was statistically correlated to age, the presence of lymph node metastases, and the presence of solid areas or psammoma bodies in the primary tumor. It was concluded that MTI could be regarded as one of the most striking and important biologic characteristics of papillary thyroid carcinoma.

Adolescent↗