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1.
Summary Thyroid tissue specimens from 27 patients with thyroid tumors were examined for thyroxine (T4) and triiodothyronine (T3) by the peroxidase-labeled antibody method. The result revealed localization of T4 in 12 of the 14 follicular adenomas, in all the 8 papillary carcinomas and in 1 of the 3 follicular carcinomas studied, and of T3 in 13 of the 14 follicular adenomas, in all the 8 papillary carcinomas and in all the 3 follicular carcinomas.In the tumor tissue, the thyroid hormones were demonstrated in the colloid substance, on the luminal surface of tumor cells and in their cytoplasm. Compared with nontumorous thyroid tissue, the tumor tissue showed localization of the hormones predominantly in the cytoplasm and to a lesser extent in the colloid substance, with conspicuous variations in tissue distribution of positive areas and intensity of staining. This tendency was more marked in thyroid carcinomas.The demonstration of T4 and T3 in routine histological paraffin sections of formalin-fixed thyroid tissues in this investigation indicates potential usefulness of thyroid hormone detection by the peroxidase-labeled antibody technique. It is an effective diagnostic tool for evaluating the functional activity of thyroid tumors as well as for determining whether a malignant growth under examination originates from the thyroid.  相似文献   

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3.
The T1 and T2 temperature dependence of female breast adipose tissue was investigated at 1.5 T in order to evaluate the applicability of relaxation‐based MR thermometry in fat for the monitoring of thermal therapies in the breast. Relaxation times T1, T2 and T2TSE (the apparent T2 measured using a turbo spin echo readout sequence) were measured in seven fresh adipose breast samples for temperatures from 25 to 65 °C. Spectral water suppression was used to reduce the influence of the residual water signal. The temperature dependence of the relaxation times was characterized. The expected maximum temperature measurement errors based on average calibration lines were calculated. In addition, the heating–cooling reversibility was investigated for two samples. The T1 and T2TSE temperature (T) dependence could be fitted well with an exponential function of 1/T. A linear relationship between T2 and temperature was found. The temperature coefficients (mean ± inter‐sample standard deviation) of T1 and T2TSE increased from 25 °C (dT1/dT = 5.35 ± 0.08 ms/°C, dT2TSE/dT = 3.82 ± 0.06 ms/°C) to 65 °C (dT1/dT = 9.50 ± 0.16 ms/°C, dT2TSE/dT = 7.99 ± 0.38 ms/°C). The temperature coefficient of T2 was 0.90 ± 0.03 ms/°C. The temperature‐induced changes in the relaxation times were found to be reversible after heating to 65 °C. Given the small inter‐sample variation of the temperature coefficients, relaxation‐based MR thermometry appears to be feasible in breast adipose tissue, and may be used as an adjunct to proton resonance frequency shift (PRFS) thermometry in aqueous tissue (glandular + tumor). Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   

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5.
In the most simplistic terms, immune tolerance can be envisioned as a balance with autoreactive cells that arise naturally in all individuals on one side and regulatory mechanisms designed to counter those autoreactive processes on the other. A tilt of the balance toward the autoreactive side, either by increasing the number or function of autoreactive cells or by diminishing regulatory mechanisms, is manifested as autoimmunity. In contrast, tilting of the balance toward increased regulation could conceivably cause immunodeficiency. Regulatory T cells (TREG), and particularly the naturally arising CD4+CD25+ subset of TREG cells, provide a substantial component of the autoimmune counterbalance. The identification of forkhead box P3 (FOXP3) as a critical determinant of CD4+CD25+ TREG development and function has provided new opportunities and generated expanded interest in studying the delicate balance between autoimmunity and regulatory mechanisms in human autoimmune diseases. Identification of both human and mouse syndromes in which FOXP3 is mutated, and consequently CD4+CD25+ TREG cells are absent, has led to a rapid accumulation of knowledge regarding TREG development and function over the past 5 years. The recent development of antibody reagents to specifically identify CD4+CD25+ TREG cells by their FOXP3 expression has provided new tools to identify these elusive cells and investigate their role in human disease. This review will focus on the current state of knowledge regarding the role of TREG in human autoimmune diseases and on specific human immunodeficiencies that provide interesting models of autoimmunity.  相似文献   

6.
Physiological changes during normal pregnancy are characterized by an inflammatory immune response and insulin resistance. Therefore, we hypothesize that gestational diabetes mellitus (GDM) may be caused by an inappropriate adaption of the maternal immune system to pregnancy. In this study we examined the role of regulatory T cell (Treg) differentiation for the development of GDM during pregnancy. We used six-colour flow cytometric analysis to demonstrate that the total CD4+CD127low+/−CD25+ forkhead box protein 3 (FoxP3+) Treg pool consists of four different Treg subsets: naive CD45RA+ Tregs, HLA-DRCD45RA memory Tregs (DR Tregs) and the highly differentiated and activated HLA-DRlow+CD45RA and HLA-DRhigh+CD45RA memory Tregs (DRlow+ and DRhigh+ Tregs). Compared to healthy pregnancies, the percentage of CD4+CD127low+/−CD25+FoxP3+ Tregs within the total CD4+ T helper cell pool was not different in patients affected by GDM. However, the suppressive activity of the total CD4+CD127low+/−CD25+ Treg pool was significantly reduced in GDM patients. The composition of the total Treg pool changed in the way that its percentage of naive CD45RA+ Tregs was decreased significantly in both patients with dietary-adjusted GDM and patients with insulin-dependent GDM. In contrast, the percentage of DR-memory Tregs was increased significantly in patients with dietary-adjusted GDM, while the percentage of DRlow+ and DRhigh+ memory Tregs was increased significantly in patients with insulin-dependent GDM. Hence, our findings propose that alterations in homeostatic parameters related to the development and function of naive and memory Tregs may cause the reduction of the suppressive capacity of the total Treg pool in GDM patients. However, as this is an exploratory analysis, the results are only suggestive and require further validation.  相似文献   

7.
Summary The low level of triiodothyronine (T3) in nonthyroidal illnesses (NTI) has been attributed to the decreased peripheral conversion of thyroxine (T4) to T3; patient's serum lipids decreased the conversion in a cell-free system. The objective of our study was to determine whether patients' serum lipids, whose content was elevated 2.5-fold above the reference serum value, and oleic acid affected the uptake of T4 and its conversion to T3 by rat hepatocytes in culture, thereby providing information on the cell's response to these processes. Serum ether extracts and oleic acid (0.1 mol/l) were incubated with cells followed by assessment of T4 uptake and conversion of T4 to T3. The mean T4 uptake in the presence of ether extracts of NTI patients' or normals' sera were similar (112±15% and 110±24%, respectively). There was no difference in the T4 to T3 conversion between the patient and normal groups (90 ±14%); oleic acid also did not influence the conversion (96.7 ± 1.6%). Uptake and conversion in the absence of either extracts and oleic acid were controls. These results suggest that serum lipids from NTI patients and normal subjects exercise qualitatively and quantitatively almost similar influences on T4 uptake and its conversion to T3; oleic acid is not an inhibitor of T4 uptake and T4 to T3 conversion in the rat hepatocyte. Since hepatocytes actively process fatty acids, their influence on intracellular conversion of T4 is not equitable with T4 conversion using the cell-free system. Our results do not support the hypothesis that abnormal lipid metabolism in NTI impairs hepatic T4 to T3 conversion.Abbreviations NTI nonthyroidal illness - T3 triiodothyro-nine - TT3 total T3 - rT3 reverse T3 - T4 thyroxine - TT4 total T4 - FT4 free T4  相似文献   

8.
Since the organic anion transporter-1 (OAT1) has been implicated in cortisol release from bovine and rat adrenal zona fasciculata cells, we addressed the question of whether OATs are present in human adrenal cortical cells. In the human adrenal cell line NCI-H295R, 24-h cortisol secretion increased up to 30-fold on exposure to forskolin. Incubation of forskolin-treated cells for 24 h with the OAT substrates probenecid, p-aminohippurate (PAH), glutarate or cimetidine inhibited cortisol release partly. RT-PCR did not reveal expression of human OAT1 and OAT2, but OAT3 and OAT4 mRNAs were detected in both NCI-H295R cells and human adrenal tissue. When human OAT3 (hOAT3) and hOAT4 were expressed in Xenopus laevis oocytes, only hOAT3 showed [3H]cortisol uptake in excess of that of water-injected control oocytes. Cortisol uptake via OAT3 was saturable with an apparent Kt of 2.4 µM. In NCI-H295R cells, [3H]estrone sulphate uptake was saturable, cis-inhibited by OAT substrates and trans-stimulated by preloading with glutarate or cortisol. Likewise, [3H]PAH uptake was cis-inhibited by estrone sulphate and trans-stimulated by preloading the cells with PAH, glutarate or cortisol, indicating functional expression of OATs in the plasma membrane of NCI-H295R cells.  相似文献   

9.
Follicular helper T cells (Tfh) are located within germinal centers of lymph nodes. Cognate interaction between Tfh, B cells, and IL‐21 drives B cells to proliferate and differentiate into plasma cells thereby leading to antibody production. Tfh cells and IL‐21 are involved in infectious and autoimmune diseases, immunodeficiencies, vaccination, and cancer. Human peripheral blood CXCR5+ CD4+ T cells comprise different subsets of Tfh‐like cells. Despite the importance of the IgE response in the pathogenesis of allergic disorders, little is known about the role of follicular and blood Tfh cells and IL‐21 in human and experimental allergic disease. Here, we review recent advances regarding the phenotypic and functional characteristics of both follicular and blood Tfh cells and of the IL‐21/IL‐21R system in the context of allergic disorders.  相似文献   

10.
ABSTRACT

An amperometric biosensor based on L-aminoacid oxidase is proposed for enantioselective assay of (+)-3,3′,5-triiodo-L-thyronine (L-T3) and (+)-3,3′,5,5′-tetraiodo-L-thyronine (L-T4), due to the fact that only the L enantiomer has the hormonal activity. The construction of the amperometric biosensor is simple and reproducible. The analytical information obtained from enantioselective analysis are reliable. The RSD <1% assured by using the amperometric biosensors for L enantiomers assay as raw materials, and from tablets, demonstrated their suitability for the analysis of T3 and T4 at ppb concentration levels.  相似文献   

11.
Objective:  Cells of the immune system (peritoneal lymphocytes, monocytes, granulocytes and mast cells as well as thymocytes) contain triiodothyronine (T3). The aim of the present experiments was to study whether thyrotropic hormone (TSH) regulates or not the T3 concentration of these cells. Methods:  Peritoneal fluid and thymus cells of adult rats were studied by immunocytochemistry, combined with flow cytometry for triiodothyronine content with or without in-vitro TSH treatment. In addition, adult female CD1 mice were treated in vivo with 10 or 40 mU TSH and after 1 hour peritoneal immune cells were studied using the above mentioned method. Results:  Both in vitro (in rat) and in vivo (in mice) TSH treatments significantly elevated the T3 content in each cell type. In vitro TSH 0.1 mU/ml cell suspension was enough to provoke about 50 % increase in T3 production. Conclusion:  T3 concentration in immune cells seems to be regulated by TSH, similarly to the T3 in the thyroid. Considering the large number of immune cells in an organism, TSH regulation of their T3 content could have an important physiological and pathological role, both in and beyond the immune system. Received 15 April 2008; returned for revision 19 May 2008; received from final revision 20 May 2008; accepted by I. Ahnfeld-R?nne 23 June 2008  相似文献   

12.
Zusammenfassung Bei 23 Kindern mit primärer Hypothyreose, die mit Thyroxin (T4) und Trijodthyronin (T3) enthaltenden Kombinationspräparaten behandelt worden waren, wurden TRH-Teste, TBI, T3- und T4-Bestimmungen durchgeführt. Die T3/T4-Quotienten wurden berechnet. 7 von 10 Patienten mit TRH-refraktären TSH-Werten und normalen T4-Spiegeln wiesen überhöhte T3-Werte auf. Bei 6 von diesen Patienten konnten pathologisch überhöhte T3/T4-Quotienten beobachtet werden. Eine TRH-refraktäre TSH-Suppression wurde nur bei hohen T4-Werten gefunden. Nach einer Reduktion der Substitutionsdosis normalisierten sich die überhöhten T3-Spiegel. Die Befunde zeigen, daß nicht nur die T4-Werte sondern auch die TSH- und T3-Spiegeln unter der Behandlung mit Schilddrüsenhormonen kontrolliert werden sollten. Die Durchführung der Substitutionstherapie der Hypothyreose mit T3/T4-Kombinationspräparaten im Verhältnis 1:4 sollte überdacht werden.  相似文献   

13.
This study determines levels of regulatory T cells (Tregs), naive Tregs, immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)‐infected patients receiving prolonged highly active anti‐retroviral therapy (HAART) who have known thymic output, and explores if naive Tregs may represent recent thymic emigrant Tregs. HIV‐infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of Tregs (CD3+CD4+CD25+CD127low), naive Tregs (CD3+CD4+CD25+CD45RA+) and activation markers (CD38+human leucocyte antigen D‐related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (TREC) content in CD4+ cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of Tregs were significantly higher in HIV‐infected patients compared with controls, both after 1 and 5 years of HAART (P < 0·001), despite fully suppressed HIV‐RNA and normalization of both CD4 counts, immune activation and cytokine patterns. Furthermore, levels of naive Tregs were elevated significantly in HIV‐infected patients (P < 0·001) and were associated with thymic output measured as the TREC frequency in CD4+ cells (P = 0·038). In summary, Treg levels in HIV‐infected patients are elevated even after 5 years of HAART. Increased thymic production of naive Tregs may contribute to higher Treg levels in HIV‐infection.  相似文献   

14.
Summary T4-, T3- and reverse-T3 concentrations were measured in the sera of 365 subjects beyond the age of 65 in order to evaluate if the decrease of serum T3 frequently observed in old age can be attributed to old age per se or to concomitant non-thyroidal disease. The results obtained from a carefully selected healthy group of elderly people show that 1) total and free T3 levels are lower in senescence but well within the range for euthyroidism in younger healthy controls; 2) the decrease of serum T3 is more pronounced and occurs earlier in healthy old males than in females, so that for subjects over the age of 75, the upper limit for euthyroidism has to be adjusted by 10% in women and by 20% in men; and 3) there is no low T3 syndrome characterized by decreased serum T3 and increased serum reverse T3, solely due to old age.Turnover kinetics have shown the daily production of T4 and T3 in old age to decrease by 20 µg and 10 µg, respectively, and an increased T3 metabolic clearance not to account for the reduction of serum T3 concentrations. Combined stimulation tests with TSH and TRH showed that the functional reserve of the thyroid gland to produce T3 is maintained in old age. The first step in the sequence of events may be seen in an impairment of TSH secretion leading to an adaptation of the amount of thyroid hormones to a reduced mass of metabolically active body tissue in old age.  相似文献   

15.
The function of CD4+ T cells with regulatory activity (Tregs) is the down-regulation of immune responses. This suppressive activity may limit the magnitude of effector responses, resulting in failure to control human immunodeficiency virus 1 (HIV-1) infection, but may also suppress chronic immune activation, a characteristic feature of HIV-1 disease. We evaluated the correlation between viral load, immune activation and Tregs in HIV-1-infected children. Eighty-nine HIV-1-infected children (aged 6–14 years) were included in the study and analysed for HIV-1 plasmaviraemia, HIV-1 DNA load, CD4 and CD8 cell subsets. Treg cells [CD4+ CD25highCD127lowforkhead box P3 (FoxP3high)] and CD8-activated T cells (CD8+CD38+) were determined by flow cytometry. Results showed that the number of activated CD8+CD38+ T cells increased in relation to HIV-1 RNA plasmaviraemia (r = 0·403, P < 0·0001). The proportion of Tregs also correlated positively with HIV-1 plasmaviraemia (r = 0·323, P = 0·002), but correlated inversely with CD4+ cells (r = −0·312, P = 0·004), thus suggesting a selective expansion along with increased viraemia and CD4+ depletion. Interestingly, a positive correlation was found between the levels of Tregs and CD8+CD38+ T cells (r = 0·305, P = 0·005), and the percentage of Tregs tended to correlate with HIV-1 DNA load (r = 0·224, P = 0·062). Overall, these findings suggest that immune activation contributes to the expansion of Treg cells. In turn, the suppressive activity of Tregs may impair effector responses against HIV-1, but appears to be ineffective in limiting immune activation.  相似文献   

16.
The effect of PGE1 on the uptake of glucose and the release of FFA and glycerol before and after sympathetic nerve stimulation (4 cps) was investigated in perfused canine subcutaneous adipose tissue in situ. Glucose uptake was significantly increased by PGE1 at all concentrations used (5 times 10-10 to 7 times 10-7 M in blood). The effect of PGE1 on the release of FFA and glycerol in unstimulated adipose tissue was inconsistent. Increases as well as decreases were observed. Lipolysis, as measured by glycerol release, induced by nerve stimulation was inhibited dose-dependently. A 50 per cent inhibition was produced by approximately 1.2 times 10-7 M PGE1. Stimulated FFA release was also inhibited but there was no clear dose-response relationship. It is concluded that PGE1 has similar effects in canine subcutaneous adipose tissue with an intact blood supply as are known to be produced in vitro.  相似文献   

17.
As developments in RF coils and RF management strategies make performing ultra‐high‐field renal imaging feasible, understanding the relaxation times of the tissue becomes increasingly important for tissue characterization, sequence optimization and quantitative functional renal imaging, such as renal perfusion imaging using arterial spin labeling. By using a magnetization‐prepared single‐breath‐hold fast spin echo imaging method, human renal T1 and T2 imaging studies were successfully performed at 7 T with 11 healthy volunteers (eight males, 45 ± 17 years, and three females, 29 ± 7 years, mean ± standard deviation, S.D.) while addressing challenges of B1+ inhomogeneity and short‐term specific absorption rate limits. At 7 T, measured renal T1 values for the renal cortex and medulla (mean ± S.D.) from five healthy volunteers who participated in both 3 T and two‐session 7 T studies were 1661 ± 68 ms and 2094 ± 67 ms, and T2 values were 108 ± 7 ms and 126 ± 6 ms. For comparison, similar measurements were made at 3 T, where renal cortex and medulla T1 values of 1261 ± 86 ms and 1676 ± 94 ms and T2 values of 121 ± 5 ms and 138 ± 7 ms were obtained. Measurements at 3 T and 7 T were significantly different for both T1 and T2 values in both renal tissues. Reproducibility studies at 7 T demonstrated that T1 and T2 estimations were robust, with group mean percentage differences of less than 4%. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   

18.
T regulatory cells are fundamental in the maintenance of immune homeostasis and self-tolerance. Experimental models suggest the existence of two functional types of Treg cells designated naturally occurring and induced. Interest in Treg cells increased with evidence from experimental mouse and human models demonstrating that the immunosuppressive potential of these cells can be utilized in the treatment of various pathological conditions. The existence of a subpopulation of suppressive T cells was the subject of significant controversy among immunologists for many years. T regulatory cells limit immune activation through a variety of direct and indirect interactions, many of which are yet to be determined. Fully understanding Treg cells biology will lead us to harnessing the capacity of these cells in order to develop strategies to prevent autoimmune disorders and tolerance to transplantation. Efficient isolation, expansion and cryopreservation strategies that comply with Good Manufacturing Practice (GMP) guidelines are prerequisites for the clinical application of human CD4+ CD25+ CD127low FOXP3+ regulatory T cells.  相似文献   

19.
It is generally accepted that the amount and distribution of adipose tissue (AT) in the human body play an important role in the pathogenesis of metabolic diseases. In addition, metabolic effects of released saturated fatty acids (FAs) in blood are known to be more critical than those of unsaturated FAs. However, little is known about the variability in unsaturation of FAs in various AT compartments. The aim of this prospective study was the assessment of mono‐ and polyunsaturated FAs in various AT compartments by localized 1H‐MRS in order to obtain insight into the intra‐ and interindividual variability. Associations of FA unsaturation with intrahepatic lipids (IHLs), insulin sensitivity and related AT volumes were analyzed. Fifty healthy Caucasians (36 male, 14 female) participated in this study. Spectroscopic examinations were performed in subcutaneous adipose tissue in the neck (SCATneck), abdominal deep subcutaneous adipose tissue (DSCAT), abdominal superficial subcutaneous adipose tissue (SSCAT), visceral adipose tissue (VAT), tibial bone marrow (BM) and subcutaneous adipose tissue of the lower leg (SCATcalf) at 3 T. Unsaturated index (UI) was calculated by the ratio of olefinic and methyl resonances, polyunsaturated index (PUI) by the ratio of diallylic and methyl resonances. Volumes of AT compartments (by T1‐weighted MRI) and IHL (single‐voxel STEAM) were assessed at 1.5 T, insulin sensitivity by an oral glucose tolerance test. UI was highest for SCATcalf (0.622) and lowest for BM (0.527). Highest PUI was observed for SSCAT (0.108), lowest for BM (0.093). Significant intraindividual differences between UIs—but not PUIs—are present for most compartments. There is a non‐significant trend for higher UI in males but otherwise no correlation to anthropometric data (age, BMI). A significant negative correlation between UI and AT volume was observed for VAT but for none of the other compartments. Neither UIs nor PUIs show a relation with IHL; insulin sensitivity is significantly correlated to UI in BM (p < 0.01). Unsaturation indices in several distinct AT compartments are location dependent. Our cohort showed only moderate gender‐related differences, with a trend towards less unsaturated FAs (mainly PUI) in females. In BM, insulin resistant subjects are characterized by a higher UI compared with the insulin sensitive ones. Further studies in larger cohorts are necessary to gain further insight into unsaturation of AT.  相似文献   

20.
Subcutaneous (SAT) and visceral adipose tissue (VAT) differ in composition, endocrine function and localization in the body. VAT is considered to play a role in the pathogenesis of insulin resistance, type 2 diabetes, fatty liver disease, and other obesity‐related disorders. It has been shown that the amount, distribution, and (cellular) composition of adipose tissue (AT) correlate well with metabolic conditions. In this study, T1 relaxation times of AT were measured in severely obese subjects and compared with those of healthy lean controls. Here, we tested the hypothesis that T1 relaxation times of AT differ between lean and obese individuals, but also between VAT and SAT as well as superficial (sSAT) and deep SAT (dSAT) in the same individual. Twenty severely obese subjects (BMI 41.4 ± 4.8 kg/m2) and ten healthy lean controls matched for age (BMI 21.5 ± 1.9 kg/m2) underwent MRI at 1.5 T using a single‐shot fast spin‐echo sequence (short‐tau inversion recovery) at six different inversion times (TI range 100–1000 ms). T1 relaxation times were computed for all subjects by fitting the TI‐dependent MR signal intensities of user‐defined regions of interest in both SAT and VAT to a model function. T1 times in sSAT and dSAT were only measured in obese patients. For both obese patients and controls, the T1 times of SAT (275 ± 14 and 301 ± 12 ms) were significantly (p < 0.01) shorter than the respective values in VAT (294 ± 20 and 360 ± 35 ms). Obese subjects also showed significant (p < 0.01) T1 differences between sSAT (268 ± 11 ms) and dSAT (281 ± 19 ms). More important, T1 differences in both SAT and VAT were highly significant (p < 0.001) between obese patients and healthy subjects. The results of our pilot study suggest that T1 relaxation times differ between severely obese patients and lean controls, and may potentially provide an additional means for the non‐invasive assessment of AT conditions and dysfunction. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   

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