免疫去除血清高丰度蛋白对组织蛋白质组鉴定的影响

目的分析去除组织中血清高丰度蛋白对组织蛋白质组鉴定的影响。方法用去除12种血清高丰度蛋白抗体柱处理人甲状腺和垂体组织样品,所得到的低丰度蛋白和原样分别进行液质联用分析,分别进行多肽和蛋白质水平的定性定量分析。结果甲状腺和垂体组织中血清高丰度蛋白分别被除去了92.11%±12.87%和78%±25%。所鉴定到的多肽和蛋白与原样品相比,甲状腺组织的非冗余性多肽提高了70%、蛋白数目提高了16.5%,垂体的非冗余性多肽提高了21.9%,鉴定蛋白数目无明显变化。结论去除组织中的血清高丰度蛋白法可以显著的提高肽段和蛋白的鉴定效率,更适用于血管密集的样品。

Pharmacokinetics of recombinant human parathyroid hormone after subcutaneous administration in Rhesus monkeys by immunoradiometric assay

The purpose of this research was to study the pharmacokinetics and the bioavailability of recombinant human parathyroid hormone [rhPTH （1-34）] in Rhesus monkeys after single and multiple subcutaneous administration. An immunoradiometric assay （IRMA） was used to determine the plasma drug concentration of rhFFH （1-34） after giving single dose of 10, 20 and 40 ug/kg and daily dose of 40 ug/kg for 7 d by subcutaneous administration, and intravenous injection of 20 ug/kg in Rhesus monkeys. The pharmacokinetic parameters were calculated by noncompartmental analysis. The drug plasma level quantitation range was from 0.027 to 2.22 ng/mL. The intra- and inter-assay precision （CV） of analysis were less than 15%, and the average recovery was about 93.0% ± 8.6% - 116.5% ± 14.0%. After subcutaneous administration of rhPTH（1-34） at dose of 10, 20 and 40 ug/kg, the average Tmax was 0.67, 0.5 and 0.83 h, Cmax were 1.85 ± 0.05, 3.23 ± 0.25 and 7.15 ± 1.19 ng/mL, the AUC（0-∞） were 3.4 ± 0.6, 10.7 ± 1.3 and 12.6 ± 1.5 ng/h/mL, and terminal-phase elimination T1/2 were 0.72 ± 0.10, 1.15 ± 0.10 and 1.03 ± 0.06 h, respectively. The absolute bioavailability of rhPTH （1-34） was 46.96% after subcutaneous administration of 20 ug/kg. There was no evidence of accumulation during systemic exposure of rhPTH （1-34） upon multiple dosing in Rhesus monkeys. The IRMA assay method provide reasonable sensitivity and specificity for the pharrnacokinetic study of rhPTH （1-34） after subcutaneous or intravenous administration in Rhesus monkeys. The pharmacokinetic characteristic of rhPTH （1-34） in monkeys shows linear relationship with the dose administered subcutaneously.

Involvement of chromatin and histone acetylation in the regulation of HIV-LTR by thyroid hormone receptor

The HIV-1 LTR controls the expression of HIV-1 viral genes and thus is critical for viral propagation and pathology. Numerous host factors have been shown to participate in the regulation of the LTR promoter. Among them is the thyroid hormone (T3) receptor (TR). TR has been shown to bind to the critical region of the promoter that contain the NFbB and Sp1 binding sites. Interestingly, earlier transient transfection studies in tissue culture cells have yielded contradicting conclusions on the role of TR in LTR regulation, likely due to the use of different cell types and/or lack of proper chromatin organization. Here, using the frog oocyte as a model system that allows replication-coupled chromatin assembly, mimicking that in somatic cells, we demonstrate that unliganded heterodimers of TR and RXR (9-cis retinoic acid receptor) repress LTR while the addition of T3 relieves the repression and further activates the promoter. More importantly, we show that chromatin and unliganded TR/RXR synergize to repress the promoter in a histone deacetylase-dependent manner.

Retrospective Analysis of Diagnosis by Intraoperative Frozen Section and Routine Paraffin Embedded Tissue in 638 Thyroid Disease Patients

OBJECTIVE To summarize a common pathogenefic condition, the pathologic characteristics shown in frozen section and our experience utilizing 2 different common thyroid diseases （TD）. diagnostic methods in cases of METHODS Data from 638 cases with frozen sections from thyroid tissue were retrospectively analyzed. The intraoperative frozen sections of the patients and postoperative diagnostic results of routine paraffin sections were compared. RESULTS In the 683 patients, the gender ratio of females to males was 2.64 ： 1, and the ratio between the patients with nodular goiter （NG） and the patients with thyroid adenoma was 1.5 ： 1. The oldest age group of patients with thyroid cancer （TC） ranged from 40 to 49 years. Frozen section pathologic examination has been employed more and more in the diagnosis of thyroid diseases, and the detection rate of TC has increased year by year, i.e., the rate increased to 6.45%, 7.58%, 14.55% and 16.57%, respectively, in 2005, 2006, 2007 and 2008. Thyroid papillary carcinoma （TPC） was the most commonly seen malignant tumor of the thyroid （MTT）, which accounted for approximately 94.8% of MTTs and 11.44% of the total TDs. Micropapillary carcinoma accounted for 27.4% of TPC, and multifocal carcinomas accounted for 15.58% of TCs. Many of the TCs （19.48%） were complicated by benign diseases such as adenoma, NG and thyroiditis. The coincidence rate of diagnoses made by frozen section and paraffin embedding for thyroid disease was 98.59%. Calcification was rather common in NG and TPC, and there were significant differences in psammoma bodies （PMB） between the calcifications of TPC and NG （P 〈 0.01）. CONCLUSION TPC ranks first in the incidence of MTTs and accounts for 94.8% of all MTTs. About 1/4 of TPCs are micropapillary carcinoma, while 1/5 are accompanied by benign disease, such as adenorna, NG and thyroiditis. PMB are of importance and of significance in the diagnosis of TPC.

Expression and significance of ER and PR in differentiated thyroid carcinoma

Objective： The aim of the study was to investigate the relationship between expressions of estrogen receptor （ER）, progesterone receptor （PR） and gender, age, tumor size, lymph node metastasis, capsular invasion and histological type of differentiated thyroid carcinoma （DTC）. Methods： Seventy cases of DTC who received surgery in our hospital （No. 401 Hospital of People＇s Liberation Army, Qingdao, China） between January 2008 and December 2011 were selected. Among them, 61 cases were papillary carcinoma and 9 cases were follicular carcinoma. Twenty cases were normal thyroid tissue adjacent to the tumor which was used as control. Immunohistochemical SP method was employed to detect the expression of ER and PR. Results： The positive rates of ER and PR in tumor tissues of DTC patients were 21.4% （15/70） and 31.4% （22/70）, respectively, and no expression of ER or PR were founded in normal thyroid tissue （P 〈 0.01）. The expressions of ER and PR were related to the lymph node metastasis and capsular invasion （X2 = 16.913 and 6.327, P 〈 0.05; x2 = 7.516 and 12.727, P 〈 0.05）. No relationship was observed between the expressions of EPJPR and gender, age, and histological type （P 〉 0.05） of DTC patients. Conclusion： The expression levels of ER and PR in the tumor tissue of DTC patients were higher than those in the normal thyroid tissue nearby the tumor. Therefore, ER and PR expression might be clinical markers for DTC and its prognosis.

Clinical significance of HBME-1,Galectin-3,and CK19 expression and the status of BRAF mutation in papillary thyroid carcinoma

Objective The aim of this study was to explore the clinical significance of the expression of proteins human bone marrow endothelial cell markers(HBME-1), Galectin-3, and cytokeratin19(CK19), as well as the status of v-raf murine sarcoma viral oncogene homolog B1(BRAF) mutation in papillary thyroid carcinoma(PTC). Methods Immunohistochemical staining was performed in 82 specimens each of PTC and papillary benign lesions to detect the expression of HBME-1, Galectin-3, and CK19. Polymerase chain reaction(PCR) and gene sequencing were performed on 60 specimens each of PTC and papillary benign lesions to detect the status of BRAF mutation. Results The positive expression ratios of HBME-1, Galectin-3, and CK19 in PTC were 98.8%, 97.6% and 100% respectively, which were significantly higher than the expressions in papillary benign lesions(P < 0.05). No significant relationship was observed between the expression of these makers and the clinicopathological features of PTC. The sensitivity of co-expression of HBME-1 and CK19 or HBME-1 and Galectin-3 as diagnostic criteria of PTC was 99.9%, with a specificity of 95.4%. BRAF mutation was detected in 40 of 60 PTC(66.7%) specimens. There was a statistical difference in BRAF mutations between PTC and papillary benign lesions(P < 0.05); there were no associations between BRAF mutation and the clinicopathological features of PTC. Conclusion Combined immunohistochemical staining of HBME-1, Galectin-3, and CK19 can further improve the sensitivity and specificity of differential diagnosis of PTC. BRAF mutation is a significant genetic event, which may have diagnostic value for PTC.

Reliability of a Tissue Microarray in Detecting Thyroid Transcription Factor-1 Protein in Lung Carcinomas

OBJECTIVE To compare the expression of the thyroid transcription factor-1 （TTF-1） in human normal adult type Ⅱ alveolar epithelial cells, embryonic pneumocytes and cancer cells of lung carcinoma and metastatic lymph nodes using a tissue microarray （TMA） along with paired conventional full sections, and to investigate the reliability of tissue microarrays in detecting protein expression in lung carcinoma. METHODS A lung carcinoma TMA including 765 cores was constructed. TTF-1 protein expression in both TMA and paired conventional full sections were detected by the immunohistochemical SP method using a monoclonal antibody to TTF-1. A PU （Positive Unit） of TTF-1 protein was assessed quantitatively by the Leica Q500MC image analysis system with results from the paired conventional full sections as controls. RESULTS There was no significance between TMA and paired conventional full sections in TTF-1 expression in different nuclei of the lung tissue. CONCLUSION TTF-1 protein expression in lung carcinoma detected by TMA was highly concordant with that of paired full sections. TMA is a reliable method in detecting protein expression.

Clinical and Pathological Features of Riedel's Thyroiditis

Objective To evaluate the clinical and pathological features of Riedel's thyroiditis(RT),and current diagnostic and treatment methods for that disease.Methods Five RT cases identified by surgery and pathological examinations at Peking Union Medical College Hospital from 1985 to 2009 were analyzed and compared with the cases reported in the literature in terms of clinical and pathological features.Immunohistochemical staining of kappa and lambda light chains was carried out for RT tissues from all the five patients.Results All the five cases were females,aged 45-55 years.Elevation of serum thyroid autoantibodies was found in only one patient,who had longer disease duration than the others.Pathological examination revealed invasive fibrosclerosis of the thyroid follicles,thyroid capsule,and the surrounding tissues.In RT tissues,the number of cells containing lambda chains was a little higher than those containing kappa chains.Conclusions RT is a rare disease which might be more common in middle-aged females than in other populations.Pathological features include the destruction of thyroid follicle,extension into surrounding tissues by inflammatory cells and fibrous tissues.Immunohistochemical staining of kappa and lambda chains could help diagnose RT.

Distinct expression profiles of transcriptional coactivators for thyroid hormone receptors during Xenopus laevis metamorphosis

The biological effects of thyroid hormone (T3) are mediated by the thyroid hormone receptor (TR). Amphibian metamorphosis is one of the most dramatic processes that are dependent on T3. T3 regulates a series of orchestrated developmental changes, which ultimately result in the conversion of an aquatic herbivorous tadpole to a terrestrial carnivorous frog. T3 is presumed to bind to TRs, which in turn recruit coactivators, leading to gene activation. The best-studied coactivators belong to the p160 or SRC family. Members of this family include SRC1/NCoA-1, SRC2/TIF2/GRIP1, and SRC3/pCIP/ACTR/AIB-1/RAC-3/TRAM-1. These SRCs interact directly with liganded TR and function as adapter molecules to recruit other coactivators such as p300/CBP. Here, we studied the expression patterns of these coactivators during various stages of development. Amongst the coactivators cloned in Xenopus laevis, SRC3 was found to be dramatically upregulated during natural and T3-induced metamorphosis, and SRC2 and p300 are expressed throughout postembryonic development with little change in their expression levels. These results support the view that these coactivators participate in gene regulation by TR during metamorphosis.

Asymptomatic giant struma ovarii in a post-menopausal female: a case report

Struma ovarii, a rare varity of ovarian neoplasm, belongs to the group of monodermic teratomas mainly composed of thyroid tissue. The preoperative diagnosis is always difficult to identify without histopathological examination. Surgery is the only treatment because malignant alteration is possible and thyroid hyperactivity or hyperthyroidism may occur. Our patient, a post-menopausal women, had unilateral, large, multiloculated ovary mass of 20 cmx 15 cm × 10 cm size without any thyroid hyper activity. The radical excision of the tumor with right ovary was preformed. Histopathological examination confirmed struma ovarii. The post-operative period was uneventful and her thyroid function remained normal.

Mixed Medullary-follicular Thyroid Carcinoma： Report of a Case and Review of the Literarture

Mixed medullary-follicular carcinomas （MMFCs） are tumors of the thyroid that display morphological and immunohistochemical features of both medullary and follicular neoplasms. These tumors are rare and less than 40 cases have been described in the literature since the early 1980s The term medullary-follicular thyroid carcinoma denotes a tumor which exhibits the features of a medullary carcinoma and shows positive expression of calcitonin on immunohistochemistry. It is a follicular-derived thyroid carcinoma and is positive for thyroglobulin expression within the same tumor. Most reported cases have lymph node involvement at the time of diagnosis. In cases having disease progression, distant metastases develop in the lung, liver, mediastinum and bone. We report a case of a male patient with mixed medullary-follicular thyroid carcinoma and a review of the literature.

Isolation and rapid genetic characterization of a novel T4-like bacteriophage

Ubiquitous on earth,bacteriophages are the most abundant entities in every ecosystem,but human knowledge about them is still limited compared with that about other forms of organisms.To enrich human knowledge and promote the utilization of bacteriophages,it is necessary to isolate and characterize as many as possible different bacteriophages.Here we describe the isolation of a T4-like bacteriophage IME08 and a rapid method for its genetic characterization.With this method we easily cloned a few random fragments of the bacteriophage genome.Sequence analysis of these random clones showed that bacteriophage IME08 shared the highest sequence similarity with T4-like Enterobacteria phage T4（94%identity）,JS98（95% identity）,JS10（95%identity） and RB14（94%identity） respectively,which suggested that IME08 belonged to T4-like bacteriophage genus.

31例甲状腺非霍奇金淋巴瘤的临床分析

目的探讨甲状腺非霍奇金淋巴瘤的预后因素和治疗。方法对31例甲状腺非霍奇金淋巴瘤进行回顾性分析。所有病例均经病理诊断为B细胞来源非霍奇金淋巴瘤,其中低度恶性12例,中度恶性13例,高度恶性1例,不能分型5例。根据AnnArbor分期,Ⅰ期9例,Ⅱ期22例。原发病灶局限于甲状腺8例,超出甲状腺包膜外18例,5例资料不全。上纵隔受侵犯12例,未受侵19例。国际预后指数(IPI)为0～1的16例,2～3的9例,6例资料不全。术后化疗7例,放疗8例,化疗加放疗10例,6例术后未行进一步治疗。结果全组5年总生存率(OS)、癌症相关生存率(CSS)和无瘤生存率(DFS)分别为64%、67%和55%。Ⅰ、Ⅱ期5年OS分别为83%、56%(P=0.190),5年CSS分别为83%、60%(P=0.110)。原发肿瘤局限于甲状腺组与超出甲状腺组的5年CSS分别为100%、56%(P=0.040)。治疗前上纵隔受侵组与未受侵组的5年OS、CSS、DFS分别为38%与80%(P=0.020)、38%与85%(P=0.003)、30%与67%(P=0.040)。IPI=0～1的低危组和IPI=2～3的中危组5年OS、CSS分别为75%与42%(P=0.040)、81%与42%(P=0.010)。病理为中高度恶性者14例,3例术后综合治疗者均无瘤存活,术后单一放疗和单化疗的失败率分别为4/7和1/3。结论原发肿瘤是否局限于甲状腺、上纵隔受侵和IPI是原发甲状腺淋巴瘤重要的预后因素;病理为中高度恶性成分者应接受综合治疗。

The expression of estrogen receptors in thyroid cancer and its significance

Objective The study aimed to detect the expression of estrogen receptors(ERs) in thyroid cancer and investigate the correlation between their expression and clinical features and different pathological types.Methods The expression of ERs in 56 samples of thyroid cancer tissues was detected by an immunochemical approach. The expression of ERs in thyroid cancer tissues and different pathological types were analyzed using the χ~2 test. Results The number of cases with positive expression of ER in thyroid cancer tissues was 36. The number of papillary thyroid cancers(PTCs) was 48, with positive expression of ERs in 32 cases. The number of follicular thyroid cancers was 4, with positive expression of ERs in 2 cases. The number of medullary thyroid cancers was 4, with negative expression of ERs in all cases. The difference between the expression and different pathological types showed statistical significance. The expression of ERs showed no correlation with sex, age, or TNM stage, with no statistical significance. However, the expression of ERs was correlated with metastasis of lymph nodes, which had statistical significance. The expression of ERs was negatively correlated with pathological types and metastasis of lymph nodes. The correlated coefficient index was –0.313 and –0.334, respectively. Conclusion The expression of ERs showed no correlation with sex, age, or TNM stage, but was negatively correlated with pathological types and metastasis of lymph nodes.

Comparison of surgical methods and prognostic factors in T4 gastric cancer

Objective： In advanced gastric carcinomas that have invaded adjacent organs, the prognosis is poor. When combined resections are performed in T4 gastric cancers, it is inconclusive as to whether or not there is an improvement in the survival rate. We compared with gastrectomy alone to analyze the prognostic factors in T4 gastric cancers. Methods： Between January 1997 and December 2004, 115 patients underwent surgery for T4 gastric cancer; we divided them into two groups： combined resections in group Ⅰ, gastrectomy alone in group Ⅱ. Surgical outcomes and clinicopathologic factors were compared and prognostic factors were evaluated. Results： Among the two groups, statistically significantly different factor was Borrmann type. The most commonly resected organ was the transverse colon, and no one post-operative morbidities developed. In the multivariate analysis, the treatment group and curability were proved to be independent prognostic factors. Conclusion： In patients with T4 gastric carcinoma, surgical gastrectomy alone approach can be beneficial. Compared with the group I, non-resection （gastrectomy alone） can be performed for a better surgical approach.

Biochemical Changes in Chronic Renal Failure Pre and Post Hemodialysis

The aim of the study was to evaluate Paraoxonase-I （PON-1）, resistin and bone mineral markers （Parathyroid Hormone （PTH）, Ca＋＋ and P） levels as biochemical marker for patients with Chronicrenal Failure （CRF）. The sample of this study consists of 100 patients and 100 apparently healthy individuals. All patients were those who were receiving Hemodialysis （HD） therapy in the dialysis unit in Kirkuk general. The levels of PON-1, Ca＋＋ were significantly lower in CRF patients pre HD when compared with healthy controls, and significantly increased in post HD as compared to pre HD, but still lower than normal controls. Serum P, resistin and PTH levels were significantly higher in CRF patients pre HD process when compared with healthy controls, and their levels were significantly decreased after HD as compared to pre HD, but remained higher than controls. PON-1 was negatively correlated with the resistin, Blood Urea （BU）, Creatinine （Cr）, PTH, but positively correlated with Ca＋＋. PON-I activity was significantly decreased in CRF patients before HD and increased after HD, but remained lower than controls. PON-1 was negatively correlated with the Body Max Index （MBI）, resistin, BU, Cr, PTH, but significantly and positively correlated with Ca＋＋.

Effect of Thyroid Hormone Deficiency on Tubulin Synthesis in Developing Chick Brain

Thyroid hormone deficiency was created artificially in chick embryos by injecting propyl-thiouracil (PTU).The tubulin was quantified by ~3H-colchicine assay(expressed as colchicine binding activity).Thyroid hormone deficiency resulted in 16％ to 28％ decline of the tubulin level in the developing chick brain from 15 to 19 days of embryonic age as compared with the control,whereas the total protein amount was not significantly affected.It suggests that thyroid hormone specifically affected the synthesis of brain tubulin.

EFFECTS OF ACUPUNCTURE ON THE PITUITARYTHYROID AXIS IN RABBITS WITH FRACTURE

PURPOSE: To observe the effects of acupuncture on the pituitary-thyroid axis in rabbits with fracture. METHOD: 36 male rabbits with a 3-mm width experimental defect in the middle segment of the left radius were randomly divided into the treatment group and control group, and the changes in serum T3, T4 and TSH contents in different weeks were investigated. RESULTS: Serum T3, T4 and TSH contents in the treatment group all were higher than those in the control group, with statistically significant differences in the contents of T4 and TSH in the second week and T3 content in the fourth week (P

Institutional experience of PTH evaluation on fine-needle washing after aspiration biopsy to locate hyperfunctioning parathyroid tissue

Assaying parathyroid hormone(PTH) in the washing liquid after fine-needle aspiration biopsy(FNAB) seems to be a valid approach to locate parathyroid tissue.PTH-FNAB was evaluated in 47 patients with a clinical picture of primary hyper-parathyroidism(PHP) and ultrasonography(US) suggestive of parathyroid lesion.The patients were subdivided into two groups on the basis of the absence or presence of US thyroid alterations.The result of PTH-FNAB was compared with those of cytology,scintigraphy and,in 24 patients,surgical outcome.PTH-FNAB samples with a value higher than that recorded in the serum and higher than our institutional cut-off were deemed to be probable samples of parathyroid tissue.Cytology proved diagnostic for benign thyroid lesions,non-diagnostic for thyroid lesions,hyperplastic parathyroid tissue,undetermined or malignant thyroid lesions and other lesions in 45%,30%,17%,4%,and 4% of cases,respectively.In 47% of cases,PTH-FNAB indicated that the sample had been taken in parathyroid tissue.In patients without US alterations,the diagnostic accuracy of PTH-FNAB was greater than that of scintigraphy.After surgery,comparison between the results of PTH-FNAB and scintigraphy,in terms of positive predictive value(PPV),revealed the superiority of PTH-FNAB;PPV was 94% for FNAB and 71% for scintigraphy,while sensitivity was 83% and 69%,respectively.PTH-FNAB evaluation after FNAB appears to be more diagnostic than cytology and scintigraphy.Of all the procedures used,PTH-FNAB appears to be the method of choice when the target is US suggestive and reachable.PTH-FNAB appears to be a useful method of guiding surgical intervention.