No causal relationship between Yersinia enterocolitica infection and autoimmune thyroid disease: evidence from a prospective study

The objective of this study was to evaluate prospectively the relationship between Yersinia enterocolitica (YE) infection and the development of overt autoimmune hypo‐ or hyperthyroidism (study A) and the de novo occurrence of thyroid antibodies (study B). This was a prospective cohort study of 790 euthyroid women who were first‐ or second‐degree relatives of autoimmune thyroid disease (AITD) patients. Follow‐up was 5 years, with annual assessments. Study A was a nested case–control study in which YE serological status was measured between cases {subjects who developed overt hypothyroidism [thyroid stimulating hormone (TSH) > 5·7 mU/l and free T4 (FT4) < 9·3 pmol/l] or overt hyperthyroidism (TSH < 0·4 mU/l and FT4 > 20·1 pmol/l)} and matched controls. For study B, 388 euthyroid women without thyroid antibodies at baseline were enrolled. The YE serological status was compared between subjects who developed thyroid peroxidase (TPO)‐antibodies and/or thyroglobulin (Tg)‐antibodies at 4‐year follow‐up and those who remained negative. For study A, the proportion of subjects positive for Yersinia enterocolitica outer membrane protein (YOP) immunoglobulin (Ig)G or YOP IgA did not differ between cases and controls at baseline. One year before the development of overt hypo‐ or hyperthyroidism, the proportion of subjects with YOP IgG was not different between cases and controls, but YOP IgA were less prevalent in cases. For study B, de novo occurrence of TPO (or TPO‐antibodies and/or Tg‐antibodies) did not differ between subjects in whom YOP IgG were positive or negative at baseline. Neither persistence nor emergence of YOP IgG at 4‐year follow‐up was associated with the occurrence of TPO‐antibodies or Tg‐antibodies. Similar results were observed with respect to YOP IgA. YE infection does not contribute to an increased risk of thyroid autoimmunity.     

Favourable effects of whey protein on acetic acid-induced ulcerative colitis in a rat model

IntroductionIn the present study, we aimed to examine the effects of the administration of whey protein through rectal enema to rats with acetic acid-induced ulcerative colitis on the pathways of nuclear-related factor-2 (Nrf-2), haem oxygenase-1 (HO-1), nuclear factor κB (NF-κB), active protein kinase-1 (AP-1), tumour necrotising factor-α (TNF-α), and cyclooxygenase-2 (COX-2), IL-6, IL-10.Material and methodsTwenty-eight rats were employed for the trial. Ulcerative colitis was induced through the use of acetic acid. The therapeutic doses of whey protein were administered rectally. Ulcerative colitis was subjected to histopathological examination and protein levels in colon tissue were measured with the Western blot method.ResultsThe significant increases observed in the levels of AP-1, COX-2, IL-6, IL-10, NF-κB, and TNF-α as markers of inflammation following the development of ulcerative colitis showed remarkable decreases along with the administration of whey protein (p < 0.05). On the other hand, we identified a decrease in the Nrf2-ARE signal pathway and HO-1 protein having protective roles in the colon inflammatory response along with the development of ulcerative colitis and activation of the Nrf2-HO-1 pathway by the whey protein.ConclusionsWhey protein modulates Nrf2/HO-1 and NF-kB pathways, thereby creating a therapeutic effect against colonic inflammation induced by acetic acid (AA) due to its anti-inflammatory effects.     

Microfilariae identified in FNA of a thyroid nodule

A patient presented with hyperthyroidism and a thyroid swelling, clinically thought to be malignant. Fine-needle aspiration of the thyroid nodule revealed microfilariae of Wuchereria bancrofti. After therapy the thyroid swelling subsided and the patient became euthyroid. The possible etiologic role of microfilariae in the genesis of the thyroid tumor and hyperthyroidism is discussed. Diagn. Cytopathol. 16:149–150, 1997. © 1997 Wiley-Liss, Inc.     

甲状腺过氧化物酶抗体在甲亢、甲状腺占位性病变诊治中的临床意义

目的观察不同临床治疗阶段甲亢、甲状腺占位性病变患者血清甲状腺过氧化物酶抗体(TPOAb)浓度的变化,探讨其临床指导价值。方法采用固相化学发光酶免疫分析法观察血清TPOAb浓度变化与甲状腺功能减退(化验室检查结果)的关系。结果89例患者中,有50例患者治疗前TPOAb正常或仅轻度增高,治疗后呈现阳性者31例,其中19例发生了甲减或亚临床型;39例治疗前TPOAb阳性,治疗后转阴2例,26例浓度降低,发生甲减3例,29例患者服用不同剂量的甲状腺片而未出现甲减或亚临床型。结论甲亢和甲状腺占位性病变患者在治疗过程可伴有TPOAb浓度的变化,TPOAb的明显增高,预示出现甲减的可能性大,TPOAb阳性的患者应被关注,高滴度TPOAb的甲亢患者治疗方案的选择要慎重。     

母源性甲亢对仔鼠肾甲状腺素受体表达的影响

目的:研究母源性甲亢对新生仔鼠肾的影响。方法:建立妊娠合并甲亢模型,取新生1、5、10和15 d仔鼠肾。分别进行解剖学及组织病理检查,采用实时定量PCR法检测甲状腺激素受体(TR)TRα_1、TRα_2、TRβ_1在肾组织中mRNA水平表达量的变化。结果:母源性甲亢仔鼠与同期对照仔鼠相比,光镜结构未见明显异常;甲亢组TRα_1的表达量略高于对照组(仔鼠1 d上调约50%,仔鼠5 d上调约32%,仔鼠15 d上调约48%);甲亢组TRα_2的表达量略高于对照组(仔鼠1 d上调约36%,仔鼠10 d上调约33%);TRβ_1的表达差异无统计学意义。结论:母源性甲亢引起甲状腺激素受体的差异表达,以TRα_1、TRα_2的变化为主,可能在甲亢引起的子代肾损伤中扮演重要角色。     

Structural and functional alterations in thyroid gland as elements of chronic endotoxicosis

Chronic endotoxicosis leads to pronounced structural changes in the thyroid gland and hypothyrosis characterized by reduced weight and activity of the thyroid parenchyma. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 12, pp. 707–711, December, 2007     

Restructuring of the thyroid gland in primary hypothyroidism under the influence of intermittent hypobaric hypoxia

We studied the effect of intermittent hypobaric hypoxia on morphofunctional characteristics of the thyroid gland during experimental hypothyroidism. Functional activity of the thyroid gland increased in the early period of hypoxia. Morphofunctional parameters reached a constant level with increasing the duration of hypoxia to 7–15 days. A new functional level was characterized by increased activity and normal function of glandular cells. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 5, pp. 588–590, May, 2008     

In vitro thyroid hormone rapidly modulates protein phosphorylation in cerebrocortical synaptosomes from adult rat brain

Thyroid hormones induced rapid changes in phosphorylation in a membrane-containing lysate of synaptosomes purified from adult rat cerebral cortex. The in vitro addition of 3,5,3'-L-triiodothyronine or L-thyroxine strongly influenced incorporation of label from [gamma-32P]-ATP into proteins in a cerebrocortical synaptosomal lysate. Incubation with 3,5,3'-L-triiodothyronine or L-thyroxine had strong biphasic dose-dependent effects on the phosphorylation of 38+/-1, 53+/-1, 62+/-1, and 113+/-1 kDa proteins (which we termed alpha, beta, gamma, and delta, respectively) and several others. Although we observed differing levels of phosphorylation among the four proteins, doses of 3,5,3'-L-triiodothyronine or L-thyroxine ranging from 1 to 30 nM caused significant dose-dependent stimulation of the phosphorylation of all of them, an effect which occurred within three minutes. In each case, the enhancement of phosphorylation diminished with higher concentrations (100 nM-1 microM) of 3,5,3'-L-triiodothyronine. In contrast, incubations with similar doses of 3,3',5'-L-triiodothyronine (reverse L-triiodothyronine) were without significant effect, indicating a specificity for 3,5,3'-L-triiodothyronine and L-thyroxine. Western blots of synaptosomal lysates incubated with 3,5,3'-L-triiodothyronine (1 nM-1 microM) demonstrated phosphorylation at the serine residues of a 112 kDa protein (matching delta) and phosphorylation at tyrosyl residues of a distinct 95 kDa protein. These data support the contention that thyroid hormones have a variety of rapid nongenomic pathways for regulation of protein phosphorylation in mature mammalian brain.     

Comparative studies on thermoresistance of protein G-binding region and antigen determinant region of immunoglobulin G in acidic colostral whey

The kinetics of the denaturation of antigen determinant (AGD) region and protein G-binding (PGB) region of bovine immunoglobulin G (IgG) in acidic colostral whey were studied by single radial Immunodiffusion (SRID) and protein G affinity chromatography (PrGAC) during the same courses of heat treatment. The kinetic and thermodynamic parameters for heat-induced denaturation of AGD and PGB regions of IgG were determined over a temperature range of 69-81°C. The denaturation reactions of both AGD and PGB regions of IgG were best described with apparent reaction order of 1.2, the activation energy values of the denaturation reactions were 159.42 kJ/mol and 235.37 kJ/mol respectively. This work suggested that the AGD region was more heat-labile than the PGB region of IgG in acidic colostral whey, Moreover, the higher values of the constant for the AGD region meant that, once the unfolding of the region started, denaturation would occur more quickly than the PGB region on IgG molecule. All these factors contributed to the fact that generally the IgG contents in the products of bovine colostrum determined by PrGAC would be higher than those by SRID.     

Induction in vitro of 72-kD heat shock protein in a continuous culture of rat thyroid cells, FRTL5.

In Graves' disease and Hashimoto's thyroiditis, the presence of 72-kD heat shock protein (hsp-72) on thyrocytes has been reported. To clarify the significance of this phenomenon, we induced the antigen in thyroid cell culture in vitro. In the FRTL5 rat cell line, which had been heated at 42.5 degrees C or treated with sodium arsenite, expression of hsp-72 was examined with immunoperoxidase staining and immunoprecipitation of the metabolically labelled protein using a specific MoAb. In the cells cultured either with or without thyrotropin (TSH), heat and chemical stresses reproducibly and dose-dependently induced hsp-72 antigen, whereas unstimulated controls had no significant immunoreactivity. Unlike in Graves' retrocular fibroblasts, hydrogen peroxide was not an effective stress in FRTL5, and the induction was not suppressed by methylmercaptoimmidazole and propylthiouracil, nor enhanced by interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). These data could not support the hypotheses that suppression of thyroid autoimmunity by thionamides is due to their modulatory action on hsp-72 expression, or that presence of that antigen in the thyroid tissues affected by autoimmunity is secondary to cytokine secretion from infiltrating immunocytes. On the other hand, coculture experiments of stressed FRTL5 cells and syngeneic Fisher rat splenocytes suggest that aberrantly expressed hsp may activate part of the thyroid-infiltrating lymphocytes and thereby aggravate autoimmune processes. The induction and detection systems of hsp-72 using FRTL5 cells would facilitate future studies, possibly utilizing human materials as well, to explore possible relations between stress proteins and thyroid autoimmunity.     

Prediction of protein functions based on function-function correlation relations

A protein function pair approach, based on protein-protein interaction (PPI) data, is proposed to predict protein functions. Randomization tests are performed on the PPI dataset, which resulted in a protein function correlation scoring value which is used to rank the relative importance of a function pair. It has been found that certain classes of protein functions tend to be correlated together. Scoring values of these correlation pairs allow us to predict the functionality of a protein given that it interacts with proteins having well-defined function annotations.The jackknife test is used to validate the function pair method. The protein function pair approach achieves a prediction sensitivity comparable to an approach using more sophisticated method. The main advantages of this approach are as follows: (i) a set of function-function correlation relations are derived and intuitive biological interpretation can be achieved, and (ii) its simplicity, only two parameters are needed.     

p27蛋白在结节性甲状腺肿和甲状腺癌中的表达及意义

目的探讨p27蛋白在结节性甲状腺肿和甲状腺癌中的变化,为研究甲状腺癌的发生机制提供参考依据。方法应用免疫组化法检测结节性甲状腺肿（61例）、结节性甲状腺肿伴增生结节（16例）、甲状腺癌（45例）、正常甲状腺组织（20例）标本中p27蛋白的表达。结果 p27蛋白表达阳性率在正常甲状腺组织为60.5%,结节性甲状腺肿为36.10%,甲状腺癌为33.3%,结节性甲状腺肿伴增生结节为0。可见,结节性甲状腺肿和甲状腺癌的p27蛋白表达阳性率与结节性甲状腺肿伴增生结节相比,差异均有统计学意义（P〈0.01）。结论结节性甲状腺肿可能通过增生结节向甲状腺癌演变。     

超敏TSH与TRH兴奋试验对亚临床甲功的诊断价值

探讨超敏TSH(s-TSH)在单次检测与通过TRH兴奋试验动态变化对亚临床甲功的诊断价值.对90例不同甲状腺疾病患者和58名正常人进行TRH兴奋试验. 58名对照组的s-TSH基础值为2.20±1.85mIU/L; 亚临床甲亢组和亚临床甲减组的s-TSH基础值分别为0.54±0.3mIU/L与9.08±6.3mIU/L, 此两组与对照组比较均有显著性差异(P＜0.01),并发现单次测定s-TSH结果在甲亢患者与对照组之间有15%的交叉; 正常生育期女性TRH兴奋试验表明, 出现△s-TSH＞30mIU/L.动态观察TRH兴奋试验结果比单次测定s-TSH结果更有助于亚临床甲功的诊断.     

Effect of arginine-vasopressin on the rat thyroid gland in vitro

Laboratory of Neuroendocrinology, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR. Institute of Cytology, Academy of Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR N. P. Bekhtereva.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 10, pp. 423–425, October, 1990.     

甲状腺肿瘤p14ARF、p53及FHIT蛋白的表达

目的探讨p14^ARF、p53及FHIT蛋白在甲状腺肿瘤组织中的表达及其意义。方法采用免疫组化S-P法检测20例甲状腺腺瘤和28例甲状腺癌组织中p14^ARF、p53及FHIT蛋白的表达。结果p14^ARF、p53及FHIT蛋白在甲状腺腺瘤和甲状腺癌中阳性率分别为90％、35．7％、15％和75％、90％、7．14％,3种蛋白在甲状腺腺瘤及甲状腺癌的表达差异均有显著性（P〈0．05）。p14^ARF、p53及FHIT蛋白的表达在甲状腺滤泡癌（FTC）与腺瘤之间,乳头状癌（PTC）与腺瘤之间差异均有显著性（P〈0．05）,p53及FHIT的表达在髓样癌（MTC）与腺瘤间差异也有显著性（P〈0．05）。p14^ARF、p53及FHIT蛋白的表达与甲状腺肿瘤的恶性进程有关,与患者年龄、性别及淋巴结转移无关。另外p14^ARF与FHIT蛋白的表达呈正相关,并且它们与p53的表达均呈负相关。结论肿瘤抑制蛋白p14^ARF和FHIT的缺失以及p53蛋白的高表达可能是甲状腺肿瘤发生的重要原因之一。联合检测p14^ARF、p53及FHIT蛋白有助于区分甲状腺腺瘤和甲状腺滤泡癌。     

Expression of promyelocytic leukaemia protein in thyroid neoplasms

AIMS: Promyelocytic leukaemia protein (PML) is an oncoprotein involved in the pathogenesis of acute promyelocytic leukaemia and is localized in distinct PML nuclear bodies. Our previous observation of overexpression of the PML in hormone-sensitive normal tissues and malignant solid tumours, including the thyroid, led to this analysis of the PML expression in various thyroid neoplasms to characterize the importance of the PML in thyroid carcinogenesis. METHODS AND RESULTS: Immunohistochemistry was performed on paraffin-embedded tissue samples from 106 thyroid neoplasms after antigen retrieval by microwave. Immunoblotting was done with fresh frozen tissues in a few tumours. The PML was strongly expressed in all papillary carcinomas in diffuse or ball-shaped patterns. In the follicular neoplasms, the PML expression was variable, but there was no significant difference between adenomas and carcinomas. In the medullary carcinomas, the PML expression was either not detectable or was lower than in non-neoplastic thyroids. Quantitatively different expression of the PML in various thyroid neoplasms was confirmed by immunoblotting. CONCLUSION: A significant difference of the PML expression according to the type of thyroid neoplasms suggests that the PML is important in papillary thyroid carcinomas, and furthermore, that PML expression may be used in differential diagnosis of thyroid neoplasms.     

化疗对乳腺癌患者甲状腺功能或结构的影响

目的探讨化疗对乳腺癌患者甲状腺功能或结构的近期影响。方法选取蚌埠医学院第一附属医院于2017年3月至2018年12月收治的40例女性初治原发性乳腺癌患者,检测并比较化疗后2和4疗程与化疗前的甲状腺功能5项(包括T3、T4、FT3、FT4和TSH)及其结构的变化。结果乳腺癌患者化疗2和4疗程后T4、FT4水平明显低于化疗前(P<0.05);患者化疗4疗程后甲状腺TI-RADS分级及其结构异常的发生率较化疗前均明显升高(P<0.05)。结论化疗后近期可引起或加重乳腺癌患者甲状腺功能或结构的异常,适时进行检查并干预可防止病情进一步发展,具有重要的临床意义。