[Melanocortin-4 receptor gene mutations associated with obesity].
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Animals↗
Biomedical subjects
Hiromasa Kobayashi
Publications and source records attributed to Hiromasa Kobayashi.
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↗
GC79/TRPS1 and tumorigenesis in humans.
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Adenoma↗
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↗
A new triterpene glucosyl ester from the fruit of the blackberry (Rubus allegheniensis).
A new triterpene glucosyl ester, rubusside A, has been isolated from the fruit of the blackberry (Rubus allegheniensis PORT.) along with a known triterpene glucosyl ester, niga-ichigoside F1. The chemical structure of rubusside A was determined on the basis of spectroscopic data as well as chemical evidence.
Esters↗
Missense mutation of TRPS1 in a family of tricho-rhino-phalangeal syndrome type III.
We report a new Japanese family with tricho-rhino-phalangeal syndrome type III (TRPS III) who have a missense mutation (Arg908Gln) of theTRPS1 gene (TRPS1) in affected individuals of the family. This study supports the notion that TRPS III results from missense mutations in exon 6 of TRPS1.
DNA-Binding Proteins↗
Antioxidant ortho-benzoyloxyphenyl acetic acid ester, vaccihein A, from the fruit of rabbiteye blueberry (Vaccinium ashei).
A new ortho-benzoyloxyphenyl acetic acid ester, called vaccihein A (1), was isolated from the fruit of rabbiteye blueberry (Vaccinium ashei). The chemical structure was determined on the basis of spectroscopic data. Compound 1 had antioxidative activity using the ferric thiocyanate method. In addition, 1 showed a scavenging effect on the stable free radical 1,1-diphenyl-2-picrylhydrazyl.
Acetates↗
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↗