To determine the content of thyroglobulin in oxyphilic cells of the thyroid, which have been considered as non-thyroglobulin producing cells, the degree of stainability of the various oxyphilic cells for thyroglobulin was compared with that of non-oxyphilic follicular cells in either same or different lesion. A total of 13 oxyphilic lesions, including three follicular adenomas containing oxyphilic cell nodules, four pure oxyphilic cell adenomas, and six Hashimoto's thyroiditis were compared with 16 of non-oxyphilic lesions such as, seven follicular adenomas, four chronic lymphocytic thyroiditis, and five Graves' disease. Many oxyphilic cells stained positively for thyroglobulin regardless of their morphologic variation, but less intensely than the usual follicular cells in follicular adenomas, chronic lymphocytic thyroiditis, and Graves' disease. The stainability of oxyphilic cells for thyroglogulin did not show any significant correlation with morphologic features, whereas in follicular adenomas, the non-oxyphilic follicular cells forming microfollicles stained less strongly for thyroglobulin than the same cells lining large mature follicles in a reproducible way. With above findings, we concluded that oxyphilic cells maintain the functional activity in terms of thyroglobulin synthesis, although the content of the thyroglobulin is less than that of non-oxyphilic colloid forming follicular cells.
Adenoma/*metabolism/pathology ; Graves Disease/*metabolism/pathology ; Humans ; Staining and Labeling ; Thyroglobulin/*biosynthesis ; Thyroid Neoplasms/pathology ; Thyroiditis, Autoimmune/*metabolism/pathology

Apoptosis is responsible for the loss of thyrocytes in autoimmune thyroiditis. Recent investigations into the pathogenesis of apoptosis have revealed that the important roles of suicide molecules expression on both thyrocytes and cytotoxic T-lymphocytes. To study the mechanism of thyrocyte loss in various forms of thyroiditis, we evaluated in situ expression patterns of CD40, Fas, and Fas-L on thyrocytes and infiltrating inflammatory cells by immunohistochemical staining of thyroid samples obtained from 49 patients (Graves' disease, n=10 : Hashimoto's thyroiditis, n=14; nonspecific lymphocytic thyroiditis, n=11; subacute granulomatous thyroiditis, n=11; normal, n=3). The role of cytotoxic T-lymphocytes was also evaluated by analyzing the expression of granzyme B along with their phenotypic characteristics. CD40 was not expressed on thyrocytes of normal controls while they showed a diffuse expression of Fas and a scattered focal expression of Fas-L. The plump thyrocytes proximal to the inflammatory infiltrates showed more intense expressions of these three molecules in various forms of thyroiditis and a close correlation was found between CD40 and Fas-L expression on thyrocytes. Unlike Fas, which was expressed on infiltrating lymphocytes in all groups, Fas-L was not expressed on infiltrating lymphocytes, except those in subacute granulomatous thyroiditis. Granzyme B expressing activated cytotoxic T-lymphocytes occupied a negligible proportion of CD8+ T-lymphocytes in various forms of thyroiditis, and no difference was found in terms of their proportions according to the type of thyroiditis. These results show the acquisition of CD40, Fas and Fas-L molecules on thyrocytes proximal to inflammatory cell aggregates and the negligible expression of granzyme B and Fas-L on the infiltrating lymphocytes, and suggest that Fas and Fas-L mediated apoptosis of thyrocytes (fratricide) may be more important than T cell-mediated cytotoxicity in various forms of thyroiditis.
Antigens, CD40/*metabolism ; Antigens, CD95/metabolism ; Apoptosis/*physiology ; Graves' Disease/*metabolism/pathology ; Human ; Membrane Glycoproteins/metabolism ; Reference Values ; Thyroiditis, Autoimmune/*metabolism/pathology

OBJECTIVETo characterize the morphological features of thyroid papillary microcarcinoma (PMC) and assess the significance of expression of CK19, HBME-1, Galectin-3, CD56 and p63 in differential diagnosis of PMC from benign thyroid lesions.

METHODSClinicopathologic features of 78 cases PMC were reviewed. Immunohistochemical analysis of CK19, HBME-1, Galectin-3, CD56, and p63 in 78 cases of PMC and 48 cases of benign thyroid lesions (18 cases of papillary hyperplasia, 17 cases of nodular goiter and 13 cases of lymphocytic thyroiditis) was conducted. The patients were followed up for from 6 to 269 months after surgical operation.

RESULTS69 cases nuclear atypia and overlapping nuclei (88.5%), 67 cases nuclear grooves (85.9%), 50 cases nuclear pseudoinclusions (64.1%) and 60 cases papillary architecture (76.9%) were detected in 78 cases of PMC. Moderate to strong co-expression of CK19, HBME-1 and galectin-3 was observed in 98.0% (50/51) in the PMC group but in none of the benign disease group. The expression of CD56 and p63 was negative in both groups. In the postoperative follow-up period of 6-269 months, 7 cases (9.0%) developed intrathyroid recurrence, 3 cases (3.8%) developed lymph node metastasis, no distant metastasis or death was observed. In 12 cases (15.4%) the PMC lesion smaller than 3 mm in diameter was not found by frozen section diagnosis.

CONCLUSIONSOverlapping nuclei, nuclear atypia, polar disorder, ground glass nuclei, nuclear grooves and nuclear pseudoinclusions are most important for the diagnosis of PMC with or without papillary architecture. The appearance of definite interstitial invasion, interstitial sclerosis and true complex papillary architecture are more helpful to make right diagnosis. Intraoperative frozen section is of limited value for a reliable diagnosis of PMC in diameter < or = 3 mm. Moderate to strong co-expression of CK19, HBME-1 and Galectin-3 is a very useful indicator for differential diagnosis of PMC from benign thyroid lesions.

Adult ; Biomarkers, Tumor ; metabolism ; CD56 Antigen ; metabolism ; Carcinoma, Papillary ; diagnosis ; metabolism ; pathology ; surgery ; Cell Nucleus ; pathology ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Galectin 3 ; metabolism ; Goiter, Nodular ; metabolism ; pathology ; Humans ; Hyperplasia ; Keratin-19 ; metabolism ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Thyroid Gland ; metabolism ; pathology ; Thyroid Neoplasms ; diagnosis ; metabolism ; pathology ; surgery ; Thyroidectomy ; methods ; Thyroiditis, Autoimmune ; metabolism ; pathology ; Transcription Factors ; metabolism ; Tumor Suppressor Proteins ; metabolism

OBJECTIVETo explore the regulatory mechanism of Xiaoyin Recipe () on the T helper 1/T helper 2 (Th1/Th2) immune balance.

METHODSThirty-six experimental animals were divided into three groups, 12 rats in each group: blank control group (B group), negative control group (N group), and Xiaoyin Recipe treatment group (T group). The latter two groups received immunization of experimental autoimmune thyroiditis (EAT), and T group were treated with Xiaoyin Recipe for a month. Then, the expression of Th1-Th2-related genes in peripheral blood mononuclear cells (PBMCs) were screened with Oligo GEArray Rat Th1-Th2-Th3 Microarray. The expressions of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), T-box expressed in T-cells (T-bet), and GATA-binding protein-3 (GATA-3) were detected by real-time polymerase chain reaction (RT-PCR).

RESULTSGene array screening showed that compared to N group, in T group after Xiaoyin Recipe treatment, 3 genes were upregulated in EAT rats, including interleukin-27 receptor alpha (IL-27rα), glomulin (Glmn), and GATA-3, while 38 genes were downregulated, such as CD28, IL-18, signal transducer, and activator of transcription 1 (STAT1), T-bet, TNF receptor superfamily member 4 (TNFRSF4), TNF ligand superfamily member 5 (TNFSF5), and TNF receptor superfamily member 5 (TNFRSF5). While RT-PCR showed that there was an increased level of TNF-α mRNA (P<0.01), an elevated ratio of T-bet/GATA-3, and a decreased level of IL-10 mRNA in PBMC of N and T group compared to B group (P <0.01); and after treatment with Xiaoyin Recipe, IL-10 mRNA level increased (P <0.01), while TNF-α mRNA level and T-bet/GATA-3 ratio decreased in T group compared to N group (P <0.01).

CONCLUSIONXiaoyin Recipe for psoriasis could induce a Th1/Th2 balance drift toward Th2 in PBMC of EAT rats and thus improve the conditions.

Animals ; Autoantibodies ; blood ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; GATA3 Transcription Factor ; genetics ; metabolism ; Gene Expression Regulation ; drug effects ; Interleukin-10 ; genetics ; metabolism ; Psoriasis ; blood ; drug therapy ; immunology ; pathology ; Rats ; Rats, Wistar ; T-Box Domain Proteins ; genetics ; metabolism ; Th1-Th2 Balance ; drug effects ; Th2 Cells ; drug effects ; immunology ; Thyroiditis, Autoimmune ; blood ; drug therapy ; immunology ; pathology ; Tumor Necrosis Factor-alpha ; genetics ; metabolism