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Biomedical subjects

Katsuji Ikekubo

Publications and source records attributed to Katsuji Ikekubo.

11 recordsLinked to original sources
PubMed2006

Evaluation of a 1 step TRAb assay for the detection of high-affinity components to hTSHR: evidences indicating superiority of the assay in the lower TRAb range.

The aim of this study was to develop an assay to selectively detect high-affinity components among TRAb. Using an rhTSHR-coated tube system, a 1 step TRAb assay method was developed that included 1) co-incubation with (125)I-bTSH, 2) a 50 microl serum sample, 3) an increased incubation volume (450 microl), and 4) a 1 hour incubation time. Sixty-one TRAb positive Graves' sera were studied. When the regular TRAb assay (Reg) results were quantitatively compared to the 1 step assay (1 step) results, certain dispersions and overestimations using the latter were seen. Further, some 1 step positive results were observed in the low Reg range. Overestimations were considered mostly due to the differences between TRAb standard and patients' serum TRAb in the binding competition against co-incubated (125)I-bTSH, which was shown from a modified assay mimicking the 1 step conditions. Therefore, the 1 step results were decided to be expressed by % inhibition against (125)I-bTSH. As for data dispersions, TRAb absorptions during the regular 1st incubation were studied. Individually, the absorption rates varied from 11 to 69%, and higher absorptions were observed in lower Reg range, especially in those negative by the 1 step. Observed 1 step positive results in the low Reg range were of interest, and 1 step/Reg ratios were calculated. The ratios with 1 step negative samples were significantly lower than those of 1 step positive samples. In conclusion, the 1 step assay was proved to detect a particular and biologically active TRAb, especially in those with low TRAb. The clinical significance of the 1 step results should be of future interest.

Antibody Affinity↗
PubMed2005

Immunoglobulin G subclasses and prolactin (PRL) isoforms in macroprolactinemia due to anti-PRL autoantibodies.

Although macroprolactinemia due to antiprolactin (anti-PRL) autoantibodies is not uncommon among hyperprolactinemic patients, the pathogenesis of such macroprolactinemia is still unknown. We examined IgG subclasses of anti-PRL autoantibodies by enzyme immunoassay, and PRL phosphorylation and isoforms by Western blotting, mass spectrometry, and two-dimensional electrophoresis in six patients with anti-PRL autoantibodies and in 29 controls. PRL-specific IgG subclasses in patients with anti-PRL autoantibodies were heterogeneous, but five of six patients showed IgG4 predominance, which is known to be produced by chronic antigen stimulation. Western blot and mass spectrometric analyses revealed that human pituitary PRL was phosphorylated at serine 194 and serine 163, whereas serine 163 in serum PRL was dephosphorylated. On two-dimensional electrophoresis, serum PRL mainly consisted of isoform with isoelectric point (pI) 6.58 in control hyperprolactinemic patients, whereas acidic isoforms (pIs 6.43 and 6.29) were also observed in patients with anti-PRL autoantibodies. Our data first demonstrate that human pituitary PRL is serine phosphorylated and partially dephosphorylated in serum, and suggest that the acidic isoforms may give rise to chronic antigen stimulation in patients with anti-PRL autoantibodies.

Adult↗
PubMed2005

Differences in TSH receptor binding and thyroid-stimulating properties between TSH and Graves' IgG. Slowly-acting TSH receptor antibody moieties in Graves' sera affect assay data.

We analyzed TSH receptor (TSHR) effects, both binding and thyroid-stimulation, of TSH and Graves' IgG. A new TRAb assay system utilizes rhTSHR coated tubes and is comprised of two step incubation, the first incubation with patient serum followed by a second incubation with 125I-bTSH. We called TRAb measured by this method as hTRAb. 125I-bTSH binding capacity of the tube was found close to saturation at 1 hr with 200 microl of 125I-bTSH. Up to 5 hr of first incubation for hTRAb assay revealed significant increases in all hTRAb activities. hTRAb was not affected by second incubation time or dose of 125I-bTSH. When 1 step incubation with 125I-bTSH and Graves' serum was performed, hTRAb again increased significantly with time. A simple competitive equilibrium model could not be applied to these ligands. Second, Graves' IgG and bTSH were compared for in vitro thyroid-stimulation sequentially up to 24 hr, measuring cAMP generation from cultured porcine thyrocytes. While bTSH yielded peak cAMP generation by 8 hr, TSAb revealed more cAMP generation by 24 hr than at 8 hr. We concluded that individual Graves' sera contain heterogeneous TRAb of variable avidities, and that slow-acting TRAb, which may lack biological activity, can be detected by prolonged incubation.

Animals↗
PubMed2005

Immeasurably low and non-TRH-stimulatable TSH associated with normal I-123 uptake in two goitrous euthyroid patients: possible existence of other thyroid-hormone regulated thyroid stimulators other than TSH.

We described two euthyroid patients with normally functioning goiters, but with persistently undetectable and non-stimulatable TSH levels. Subject 1 was a 64-year-old woman with a large diffuse goiter who has been clinically and biochemically euthyroid without any medication for at least 19 years. Subject 2 was a 31-year-old woman with a small diffuse goiter who has been euthyroid for 4 years. Both patients had persistently undetectable levels of serum TSH, TSH receptor antibodies (TRAb) and thyroid stimulating antibodies (TSAb). Their basal TSH levels were very low and their T3 responses to TRH were very diminished or absent. In contrast, the basal levels of the other pituitary hormones and their responses to LHRH, GRH and CRH stimulation were all within normal limits in both patients. MRI images of pituitary glands, 123I thyroid uptake, and thyroid scans were normal. Ectopic thyroids were not detected on (99m)TcO4- and 123I total body scans. Factors interfering with the measurement of TSH were excluded by recovery studies. In subject 1 a T3-suppression test was positive and a perchlorate discharge test was negative. In subject 2 a T3-suppression test was negative. Euthyroid Graves' disease, subclinical hyperthyroidism, destructive thyroiditis, thyrotoxicosis of extrathyroid origin, central hypothyroidism, and nonthyroidal illness were all ruled out by these observations. These results suggest that an unknown factor, such as thyrostimulin, but not TSH or TSAb, stimulates the thyroid and maintains euthyroidism, and may have a role in the regulation of the hypothalamus-pituitary-thyroid axis.

Adult↗
PubMed2005

[Guidelines for radio-iodine (131I) therapy in Graves' disease and thyroid cancer].

Radio-iodine (131I) therapy has been using in Graves' disease and well differentiated thyroid cancer. The rules of control in the discharge from radio-isotope hospital were notified in 1999 in Japan. Guideline of the 131I therapy in Graves' disease and thyroid cancer were prepared by sub-group of Japanese Society of Nuclear Medicine.

Graves Disease↗
PubMed2003

[A case report of distant lymph nodes metastases from prostate cancer imaged with 201Tl and 99mTc-MIBI].

Prostate cancer most often metastases to regional lymph nodes and bones by hematogeneous or lymphatic spread. The authors present a rare case of metastatic prostate cancer to supradiaphragmatic lymph nodes that were detected on 201Tl and 99mTc-MIBI imaging and confirmed on a CT scan. An 81-yr-old man with bilateral painful cervical lymphadenopathies was referred to our hospital with suspected thyroid cancer. The US and thyroid scan indicated no abnormalities in his thyroid gland. Both 201Tl and 99mTc-MIBI scans showed multiple areas of abnormally increased radioactivity in both supraclavicular, anterior mediastinum, and bilateral hilar regions. A CT scan also revealed multiple lymphadenopatheis in the same regions as radionuclide scans. Prostate cancer was diagnosed from the results of immunohistochemical staining for PSA examination of a biopsy specimen of the mediastinal lymph node. The serum PSA concentration was markedly elevated at 490 ng/ml (normal, < 40 ng/ml). Both 99mTc-HMDP bone and 67Ga scans were normal. All supradiaphragmatic lymph nodes on CT images disappeared 2 months after subcapsular orchiectomy and endocrine treatment with Bicalutamide. Metastatic prostate cancer should be considered when metastatic adenocarcinoma is discovered in the supraclavicular lymph nodes of elder men.

Adenocarcinoma↗
PubMed2003

[The present status of I-131 therapy for Graves' hyperthyroidism in Japan (survey by questionnaire)].

A survey on the I-131 therapy of Graves' hyperthyroidism was undertaken by questionnaire in 1,246 hospitals of Japan. One thousand and ninety seven of them (88.0%) responded to the questionnaire. In this paper, we report the results and analysis of the replies to the questionnaire. In the 121 hospitals (11.03%) of the respondents, I-131 therapy is being performed for Graves' hyperthyroidism. A gradual increase was observed in the annual number of I-131 treated Graves' disease patients during the period of 1998-2001, from 1,740 to 2,484. I-131 treatment was selected mainly for the cases with side effects from antithyroid drug (ATD) therapy, followed by the cases with complication of heart or hepatic diseases, recurrences of hyperthyroidism after surgery, radioiodine treatment, and long-term ATD treatment. The 41% of respondents used I-131 in order to restore euthyroidism, 34% aimed for hyperthyroidism and 41% used the dose properly between the two according to the patients. Administration dosage of I-131 was estimated mainly on the basis of thyroid uptake and volume in 93% of the respondents and 48% calculated the radiation dose by also determining the effective half-life in the thyroid gland. Thyroid size was estimated by scintigram (51%), US (33%), CT (22%) and palpation (12%). ATD treatment was used before I-131 administration by 70% of the respondents and 34% after radioiodine therapy. A low-iodine diet was given to the patients for a week (46%) or two weeks (47%) before I-131 administration. However, after treatment only 46% of the respondents continued low-iodine diet for a week.

Adolescent↗
PubMed2002

A case of TSH receptor antibody-positive hyperthyroidism with functioning metastases of thyroid carcinoma.

The presence of TSH receptor antibody (TRAb) is rarely responsible for hyperthyroidism due to metastatic lesions of thyroid carcinoma. A 70-year-old woman was incidentally found to be thyrotoxic around the time that external irradiation was performed for multiple bone metastases 9 years after subtotal thyroidectomy for follicular carcinoma. Hyperthyroidism persisted after oral administration of thiamazole. Relevant laboratory data were as follows: FT4 9.6 ng/L, FT3 7.3 ng/L, TSH <0.19 mU/L, TBII 70, TSAb 735, and Tg 32,000 microg/L. 131I-total body scan showed 131I accumulation in the occipital bone, cervical vertebra, thoracic vertebra, ilium, and residual thyroid gland. Since the ilium uptake (11.6) was markedly higher compared to the residual thyroid gland uptake (0.14), four subsequent 131I therapies were performed. The patient became hypothyroid, and TBII became negative. TSAb became negative after the first 131I-therapy but has increased again to 204 at present. Tg was 1,962 microg/L despite high TSH levels. 131I accumulation in the residual thyroid, cervical vertebra, and thoracic vertebra disappeared. Also 131I accumulation in the ilium has gradually decreased, but the image in the occipital bone has become markedly distinctive. This is a rare case characterized by TRAb-positive hyperthyroidism, by T3-predominant thyrotoxicosis, and by stronger accumulation of 131I in the metastatic tumor than in the residual thyroid gland. Thus, the response to TRAb and 131I-therapy is different among metastatic thyroid tissues.

Adenocarcinoma, Follicular↗
PubMed2002

A Novel homozygous missense mutation of melanocortin-4 receptor (MC4R) in a Japanese woman with severe obesity.

The melanocortin-4 receptor (MC4R) is a member of the seven membrane-spanning G protein-coupled receptor superfamily and signals through the activation of adenylyl cyclase. The MC4R mutations are the most common known monogenic cause of human obesity. However, no such mutations have been found in Japanese obese subjects. Here we report a novel homozygous missense mutation of MC4R (G98R) in a nondiabetic Japanese woman with severe early-onset obesity, which is located in its second transmembrane domain. Her birth weight was 3,360 g, and she gained weight progressively from 10 months of age. At 40 years of age, her weight reached 160 kg and a BMI of 62 kg/m(2). Her parents, who are heterozygous for the mutation, have BMIs of 26 and 27 kg/m(2). In vitro transient transfection assays revealed no discernable agonist ligand binding and cAMP production in HEK293 cells expressing the mutant receptor, indicating a severe loss-of-function mutation. This study represents the first demonstration of a pathogenic mutation of MC4R in Japan and will provide further insight into the pathophysiologic role of the hypothalamic melanocortin system in human obesity.

Adult↗
PubMed2002

[Not Available].

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Journal Article↗