コウジョウセン ニュウトウガン ト ハシモトビョウ ノ カンベツ ニ ツイテ

Introduction: Thyroid fine-needle cytology is the first line clinical method for thyroid nodule to select patients for surgery, because papillary carcinoma has diagnostic characteristics in cytology, such as nuclear enlargement, nuclear grooves and nuclear inclusions. However over-diagnosis of Hashimoto disease is well known fact to occur frequently.Materials and Methods: Morphometric analysis of cytological samples from Hashimoto disease, papillary carcinoma and benign adenomatous nodule were carried out 4 cases each using Papanicolaou stained conventional smear samples.Results: Sizes of clusters were evaluated by counting number of follicular cells in the cluster. It was larger in papillary carcinoma (63.3/cluster) and benign (43.9/cluster) than Hashimoto disease (18.9/cluster) (P=0.006). The nuclear diameter increased in Hashimoto disease and the average of the longest diameter was 6.5μm and the shortest was 5.5μm, which was overlapped with those of papillary carcinoma. The number of nuclear grooves increased from benign (<1%), Hashimoto disease (6%) to papillary carcinoma (16%).Conclusion: There are significant overlap between Hashimoto disease and papillary carcinoma morphologically. For more accurate diagnosis of Hashimoto disease may be achieved only with combined morphological features

Structural Characterization of Heme Environmental Mutants of CgHmuT that Shuttles Heme Molecules to Heme Transporters

Corynebacteria contain a heme uptake system encoded in hmuTUV genes, in which HmuT protein acts as a heme binding protein to transport heme to the cognate transporter HmuUV. The crystal structure of HmuT from Corynebacterium glutamicum (CgHmuT) reveals that heme is accommodated in the central cleft with His141 and Tyr240 as the axial ligands and that Tyr240 forms a hydrogen bond with Arg242. In this work, the crystal structures of H141A, Y240A, and R242A mutants were determined to understand the role of these residues for the heme binding of CgHmuT. Overall and heme environmental structures of these mutants were similar to those of the wild type, suggesting that there is little conformational change in the heme-binding cleft during heme transport reaction with binding and the dissociation of heme. A loss of one axial ligand or the hydrogen bonding interaction with Tyr240 resulted in an increase in the redox potential of the heme for CgHmuT to be reduced by dithionite, though the wild type was not reduced under physiological conditions. These results suggest that the heme environmental structure stabilizes the ferric heme binding in CgHmuT, which will be responsible for efficient heme uptake under aerobic conditions where Corynebacteria grow

Two ligand-binding sites in the O(2)-sensing signal transducer HemAT: Implications for ligand recognition/discrimination and signaling

We have identified a ligand (CO) accommodation cavity in the signal transducer sensor protein HemAT (heme-based aerotactic transducer) that allows us to gain single-molecule insights into the mechanism of gas sensor proteins. Specific mutations that are distal and proximal to the heme were designed to perturb the electrostatic field near the ligand that is bound to the heme and near the accommodated ligand in the cavity. We report the detection of a second site in heme proteins in which the exogenous ligand is accommodated in an internal cavity. The conformational gate that directs the ligand-migration pathway from the distal to the proximal site of the heme, where the ligand is trapped, has been identified. The data provide evidence that the heme pocket is the specific ligand trap and suggest that the regulatory mechanism may be tackled starting from more than one position in the protein. Based on the results, we propose a dynamic coupling between the two distinct binding sites as the underlying allosteric mechanism for gas recognition/discrimination that triggers a conformational switch for signaling by the oxygen sensor protein HemAT