BACKGROUND & AIMS: :Fine needle aspiration cytology (FNAC) is an important tool in the investigation of thyroid nodules and has few reported complications. We present the first report of recurrent laryngeal nerve palsy arising as a complication of thyroid nodule FNAC. This complication led to inaccurate diagnosis and unnecessarily radical surgery, with consequent increased morbidity.

背景与目标： : 细针穿刺细胞学检查 (FNAC) 是检查甲状腺结节的重要工具，几乎没有并发症的报道。我们提出了作为甲状腺结节FNAC并发症引起的喉返神经麻痹的第一份报告。这种并发症导致不准确的诊断和不必要的根治性手术，从而增加了发病率。

BACKGROUND & AIMS: :The ovarian steroid hormone estrogen (E2) elicits a multiplicity of both systemic and uterotropic responses in vivo. For example, the administration of E2 to ovariectomized (Ovx) and sexually immature rodents leads to uterine-specific inflammatory infiltrates. In this study, we quantitated the number of eosinophils and BM8+, Ia+, and CD4+ cells in uteri obtained from adult Ovx control and E2-treated C57BL/6J, C3H/HeJ, and (C57BL/6J x C3H/HeJ) (B6C3) F1 hybrid mice. All three strains exhibited a significant increase in the number of uterine eosinophils and BM8+ macrophages after E2 treatment. However, C57BL/6J and B6C3 F1 hybrid mice responded with a greater number of infiltrating eosinophils and macrophages as compared with C3H/HeJ. A similar analysis of Ia+ and CD4+ cells showed that E2 treatment either down-regulates or does not affect the number of such cells in all three strains. Genome exclusion mapping using a (C57BL/6J x C3H/HeJ) x C3H/HeJ backcross population localized Est1, the major locus controlling the number of eosinophils infiltrating the uterus after E2 treatment, to chromosome 4. In addition, suggestive linkage to marker loci on chromosomes 10 and 16 was detected and evidence for locus interaction is presented. Our results conclusively demonstrate that E2-regulated/ dependent responses can be genetically controlled, indicating that the phenotypic variation observed in both the normal and pathological effects of E2 may, in part, be due to a genetic component.

背景与目标： : 卵巢类固醇激素雌激素 (E2) 在体内引起多种全身和子宫性反应。例如，向卵巢切除 (Ovx) 和性不成熟的啮齿动物施用E2会导致子宫特异性炎症浸润。在这项研究中，我们定量了从成年Ovx对照和E2-treated C57BL/6J，C3H/HeJ和 (C57BL/6J x C3H/HeJ) (B6C3) F1杂交小鼠获得的子宫中嗜酸性粒细胞和BM8，Ia和CD4细胞的数量。E2处理后，所有这三种菌株的子宫嗜酸性粒细胞和BM8巨噬细胞数量均显着增加。然而，与C3H/HeJ相比，C57BL/6J和B6C3 F1杂交小鼠的浸润嗜酸性粒细胞和巨噬细胞数量更多。对Ia和CD4细胞的类似分析表明，E2处理下调或不影响所有三种菌株中此类细胞的数量。使用 (C57BL/6J x C3H/HeJ) x C3H/HeJ回交群体的基因组排斥图谱将Est1定位为4号染色体，Est1是控制E2治疗后子宫浸润的嗜酸性粒细胞数量的主要基因座。此外，还检测到与10号和16号染色体上的标记基因座的暗示连锁，并提供了基因座相互作用的证据。我们的结果最终证明了E2-regulated/依赖性反应可以在遗传上控制，这表明在E2的正常和病理作用中观察到的表型变异可能部分归因于遗传成分。

BACKGROUND & AIMS: :Following surgery, the hormone dependence of breast tumors is exploited for therapy using antagonists such as tamoxifen, although occasional hormone-resistant clones do appear. Another chemotherapeutic strategy uses microtubule inhibitors such as taxanes. Unfortunately, these agents elicit toxicities such as leukocytopenia, diarrhea, alopecia, and peripheral neuropathies and are also associated with the emergence of drug resistance. We have previously described a tubulin-binding, natural compound, noscapine, that was nontoxic and triggered apoptosis in many cancer types albeit at 10 mumol/L or higher concentrations depending on the cell type. We now show that a synthetic analogue of noscapine, 9-bromonoscapine, is approximately 10-fold to 15-fold more potent than noscapine in inhibiting cell proliferation and induces apoptosis following G2-M arrest in hormone-insensitive human breast cancers (MDA-MB-231). Furthermore, a clear loss of mitochondrial membrane potential, release of cytochrome c, activation of the terminal caspase-3, and the cleavage of its substrates such as poly(ADP-ribose) polymerase, suggest an intrinsic apoptotic mechanism. Taken together, these data point to a mitochondrially mediated apoptosis of hormone-insensitive breast cancer cells. Human tumor xenografts in nude mice showed significant tumor volume reduction and a surprising increase in longevity without signs of obvious toxicity. Thus, our data provide compelling evidence that 9-bromonoscapine can be useful for the therapy of hormone-refractory breast cancer.

背景与目标： : 手术后，尽管偶尔会出现激素抗性克隆，但使用他莫昔芬等拮抗剂来治疗乳腺肿瘤的激素依赖性。另一种化疗策略使用微管抑制剂，如紫杉烷。不幸的是，这些药物会引起毒性，例如白细胞减少，腹泻，脱发和周围神经病变，并且还与耐药性的出现有关。我们先前已经描述了一种微管蛋白结合的天然化合物noscapine，它是无毒的，并在许多癌症类型中触发了凋亡，尽管浓度为10 mumol/L或更高，具体取决于细胞类型。我们现在显示，在激素不敏感的人类乳腺癌 (MDA-MB-231) 中，诺司卡平的合成类似物9-溴单司卡平在抑制细胞增殖和诱导G2-M停滞后的凋亡方面比诺司卡平有效约10倍至15倍。此外，线粒体膜电位的明显丧失，细胞色素c的释放，末端caspase-3的激活以及其底物 (例如聚 (ADP-核糖) 聚合酶) 的裂解提示了内在的凋亡机制。综合起来，这些数据指出了激素不敏感的乳腺癌细胞的线粒体介导的凋亡。裸鼠的人类肿瘤异种移植物显示出显着的肿瘤体积减少和寿命的惊人增加，而没有明显的毒性迹象。因此，我们的数据提供了令人信服的证据，证明9-溴单可用于激素难治性乳腺癌的治疗。

BACKGROUND & AIMS: :In the last few years, our knowledge of genetically determined causes of short stature has greatly increased by reports of challenging patients, who offered the opportunity to study genes that play a role in growth. Since the first paper that showed the etiology of Laron syndrome [Godowski PJ, et al: Proc Natl Acad Sci USA 1989;86:8083-8087], many mutations in the growth hormone (GH) receptor have been identified. Recently, new mutations or deletions have been found in several components of the GH-insulin-like growth factor-I (IGF-I) axis: a homozygous mutation of the GH1 gene, resulting in a bio-inactive GH; mutations in the STAT5b gene, which plays a major role in the GH signal transduction; a homozygous missense mutation in the IGF-I gene; heterozygous mutations in the IGF-I receptor gene and a homozygous deletion of the acid-labile subunit gene. In this mini review, we describe the clinical and biochemical features of these genetic defects. Genetic analysis has become essential in the diagnostic workup of a patient with short stature. However, regarding the time consuming nature of molecular analysis, it is important to carefully select the patient for specific genetic evaluation. To help in this selection process, we developed flowcharts, based on the recently described patients, that can be used as guidelines in the diagnostic process of patients with severe short stature of unknown origin.

背景与目标： : 在过去的几年中，由于有挑战性的患者的报道，我们对基因确定的矮小原因的了解大大增加了，他们提供了研究在生长中起作用的基因的机会。自从第一篇显示拉隆综合征病因的论文 [Godowski PJ等人: Proc Natl Acad Sci USA 1989;86:8083-8087] 以来，已经鉴定出生长激素 (GH) 受体的许多突变。最近，在GH-胰岛素样生长因子-I (igf-i) 轴的几个组成部分中发现了新的突变或缺失: GH1基因的纯合突变，导致了具有生物活性的GH; STAT5b基因的突变，在GH信号转导中起主要作用; Igf-i基因中的纯合错义突变; Igf-i受体基因中的杂合突变和酸不稳定亚基基因的纯合缺失。在这篇小型综述中，我们描述了这些遗传缺陷的临床和生化特征。基因分析在身材矮小的患者的诊断检查中已变得至关重要。但是，关于分子分析的耗时性质，重要的是要仔细选择患者以进行特定的遗传评估。为了帮助这一选择过程，我们根据最近描述的患者开发了流程图，该流程图可作为不明原因严重矮小患者诊断过程的指南。

BACKGROUND & AIMS: :Papillary thyroid cancer (PTC), the most common thyroid malignancy, is associated with an excellent prognosis. Overall survival is more than 90%. The first-line treatment is surgical excision, and although the debate continues as to whether a total thyroidectomy or thyroid lobectomy should be recommended, most patients at the University of California, San Francisco are treated with a total thyroidectomy. Not only has this been shown to be superior for overall survival in select patient populations, but local recurrence is also significantly lower with this approach. Total thyroidectomy also optimizes the adjuvant treatment options that are unique to "differentiated" thyroid cancer because these malignant cells retain many of the features of the native thyroid follicular cell. These cellular features are used for specialized investigations and treatment options in patients with PTC. For example, PTC cells retain the ability to produce thyroglobulin, to be stimulated by thyroid-stimulating hormone (TSH), and to take up iodine. These features are vital and separate differentiated thyroid cancer from other epithelial malignancies because such features can be used in clinical follow-up (monitoring serum thyroglobulin levels, whole body radioactive iodine scans) and in the treatment of patients with PTC (TSH suppression, radioactive iodine ablation of thyroid remnant, local recurrences, and regional or distant metastases). In summary, the wide array of treatment options for patients with PTC includes surgery, radioactive iodine, thyroid hormone suppression of TSH, external beam radiation (less commonly), and rarely, chemotherapy. This continues to be an area of exciting research for emerging therapy, much of which concentrates on enhancing or re-establishing the differentiated features of the thyroid cancer cell, in an effort to optimize the adjuvant treatment options. The treatment options that are chosen depend on patient factors, disease factors, and the decisions of the patient and treatment team.

背景与目标： 甲状腺乳头状癌 (PTC) 是最常见的甲状腺恶性肿瘤，预后良好。总生存率超过90%。一线治疗是手术切除，尽管关于是否应推荐全甲状腺切除术或甲状腺叶切除术的争论仍在继续，但加利福尼亚大学旧金山分校的大多数患者都接受了全甲状腺切除术。这不仅被证明在选定的患者人群中优于总体生存率，而且这种方法的局部复发率也明显降低。全甲状腺切除术还优化了 “分化” 甲状腺癌独有的辅助治疗方案，因为这些恶性细胞保留了天然甲状腺滤泡细胞的许多特征。这些细胞特征用于PTC患者的专门研究和治疗选择。例如，PTC细胞保留产生甲状腺球蛋白，受促甲状腺激素 (TSH) 刺激以及摄取碘的能力。这些特征是重要的，并且与其他上皮恶性肿瘤分开分化的甲状腺癌，因为这些特征可用于临床随访 (监测血清甲状腺球蛋白水平，全身放射性碘扫描) 和PTC患者的治疗 (TSH抑制，放射性碘消融甲状腺残余，局部复发，和区域或远处转移)。总之，PTC患者的多种治疗选择包括手术，放射性碘，TSH的甲状腺激素抑制，外束辐射 (较少见) 以及很少的化学疗法。这仍然是新兴疗法令人兴奋的研究领域，其中大部分集中于增强或重建甲状腺癌细胞的分化特征，以努力优化辅助治疗方案。选择的治疗方案取决于患者因素，疾病因素以及患者和治疗团队的决定。

BACKGROUND & AIMS: :Different attempts were made to identify the variables that may be involved in the clinical course of cerebrovascular ischemia. In the case of stroke with mild severity (SMS), the clinical significance of neuroendocrine changes as well as of post-stroke depression (PSD) remains unknown. We therefore evaluated the presence of neuroendocrine changes in the acute and post-acute phase of SMS, and their potential role during convalescence. Serum cortisol, T4, T3, FT4, FT3, TSH and PRL levels were measured in 17 euthyroid patients with stroke on admission (day 1), following morning (day 2), 7 days and 3 months later. TSH and PRL secretion after TRH test were measured. Stroke severity on admission was determined by Scandinavian Stroke Scale (SSS). Montgomery-Asberg Depression Rating Scale (Madrs) was used for assessment of post-stroke depression. On admission, TSH and T3, were within normal limits and were greater compared to values on day 2. Lower basal TSH and decreased TSH response to TRH on day 2, were associated with stroke of greater severity. Delta-PRL after TRH on day 2 was higher in patients who develop PSD. Changes in serum thyroid hormones in SMS, reflects those of non-thyroidal illness. A mild stimulation of hypothalamic-pituitary-adrenal axis was detected. We provide evidence that PRL response to TRH, in the acute phase of stroke may be used as an index for early detection of PSD.

背景与目标： : 进行了不同的尝试来确定可能与脑血管缺血的临床过程有关的变量。对于轻度严重程度 (SMS) 的中风，神经内分泌变化以及卒中后抑郁 (PSD) 的临床意义仍然未知。因此，我们评估了SMS急性期和急性期后神经内分泌变化的存在及其在恢复期中的潜在作用。在入院时 (第1天)，第二天 (第2天)，7天和3个月后的17例甲状腺功能正常的中风患者中测量了血清皮质醇，T4，T3，FT4，FT3，TSH和PRL水平。TRH试验后测量TSH和PRL分泌。入院时卒中严重程度由斯堪的纳维亚卒中量表 (SSS) 确定。Montgomery-Asberg抑郁量表 (Madrs) 用于评估中风后抑郁。入院时，TSH和T3在正常范围内，与第2天的值相比更高。在第2天，较低的基础TSH和对TRH的TSH反应降低与严重程度更高的中风有关。发生PSD的患者在TRH后第2天的Delta-PRL较高。SMS中血清甲状腺激素的变化反映了非甲状腺疾病的变化。检测到下丘脑-垂体-肾上腺轴的轻度刺激。我们提供的证据表明，在中风急性期PRL对TRH的反应可以用作早期发现PSD的指标。

BACKGROUND & AIMS: :Granulocyte colony-stimulating factor (GCSF) administration has been linked to the development of monosomy 7 in severe congenital neutropenia and aplastic anemia. We assessed the effect of pharmacologic doses of GCSF on monosomy 7 cells to determine whether this chromosomal abnormality developed de novo or arose as a result of favored expansion of a preexisting clone. Fluorescence in situ hybridization (FISH) of chromosome 7 was used to identify small populations of aneuploid cells. When bone marrow mononuclear cells from patients with monosomy 7 were cultured with 400 ng/ml GCSF, all samples showed significant increases in the proportion of monosomy 7 cells. In contrast, bone marrow from karyotypically normal aplastic anemia, myelodysplastic syndrome, or healthy individuals did not show an increase in monosomy 7 cells in culture. In bone marrow CD34 cells of patients with myelodysplastic syndrome and monosomy 7, GCSF receptor (GCSFR) protein was increased. Although no mutation was found in genomic GCSFR DNA, CD34 cells showed increased expression of the GCSFR class IV mRNA isoform, which is defective in signaling cellular differentiation. GCSFR signal transduction via the Jak/Stat system was abnormal in monosomy 7 CD34 cells, with increased phosphorylated signal transducer and activation of transcription protein, STAT1-P, and increased STAT5-P relative to STAT3-P. Our results suggest that pharmacologic doses of GCSF increase the proportion of preexisting monosomy 7 cells. The abnormal response of monosomy 7 cells to GCSF would be explained by the expansion of undifferentiated monosomy 7 clones expressing the class IV GCSFR, which is defective in signaling cell maturation.

背景与目标： : 粒细胞集落刺激因子 (GCSF) 的施用与严重先天性中性粒细胞减少症和再生障碍性贫血中7号单体的发展有关。我们评估了GCSF的药理剂量对7号单体细胞的影响，以确定这种染色体异常是从头出现还是由于预先存在的克隆的有利扩增而出现的。7号染色体的荧光原位杂交 (FISH) 用于鉴定非整倍体细胞的小群体。当用400 ng/ml GCSF培养来自7号单体患者的骨髓单个核细胞时，所有样品均显示7号单体细胞的比例显着增加。相反，来自核型正常再生障碍性贫血，骨髓增生异常综合征或健康个体的骨髓在培养物中未显示出7号单体细胞的增加。在骨髓增生异常综合征和7号单体患者的骨髓CD34细胞中，GCSF受体 (GCSFR) 蛋白升高。尽管在基因组GCSFR DNA中未发现突变，但CD34细胞显示GCSFR IV类mRNA同工型的表达增加，这在信号细胞分化方面存在缺陷。通过Jak/Stat系统的GCSFR信号转导在7号单体CD34细胞中异常，磷酸化信号转导增加，转录蛋白激活，STAT1-P，相对于STAT3-P，STAT5-P增加。我们的结果表明，GCSF的药理剂量增加了先前存在的7号单体细胞的比例。7号单体细胞对GCSF的异常反应可以通过表达IV类GCSFR的未分化的7号单体克隆的扩增来解释，后者在信号细胞成熟方面存在缺陷。

BACKGROUND & AIMS: High-dose chemotherapy often requires hematopoietic progenitor cell reinfusion, but drugs with extramedullary dose-limiting toxicity may be administered in the high-dose range by simple growth factor support. In this study, we evaluated the feasibility and toxicity of a three-drug high-dose regimen supported by recombinant human granulocyte colony-stimulating factor (rhG-CSF). Ten patients with histologically proven malignancy were enrolled. Eight had breast cancer, one non-Hodgkin's lymphoma, and one a mediastinal tumor of unknown origin. The regimen included cyclophosphamide (C) 5 g/m2, etoposide (E) 1.5 g/m2, and cisplatin (P) 150 mg/m2 (CEP), administered in a 3-day schedule followed by rhG-CSF, 300 micrograms once a day, beginning from day +5 (36 h after the end of chemotherapy). The cycle was repeated as clinically needed up to three times. After the first course, hematologic recovery was rapid and complete without documented infections, and no relevant extramyeloid toxicities were observed. Eight of 10 patients received a second course with comparably low toxicity, and three of them received a third course. We concluded that CEP therapy can be administered safely and even repeatedly, by simple growth factor support, in good performance status cancer patients.

背景与目标： 大剂量化疗通常需要造血祖细胞回输，但具有髓外剂量限制毒性的药物可以通过简单的生长因子支持在高剂量范围内施用。在这项研究中，我们评估了由重组人粒细胞集落刺激因子 (rhG-CSF) 支持的三药大剂量方案的可行性和毒性。纳入了10例经组织学证实为恶性肿瘤的患者。8人患有乳腺癌，1人患有非霍奇金淋巴瘤，1人患有不明原因的纵隔肿瘤。该方案包括环磷酰胺 (C) 5g/m2，依托泊苷 (E) 1.5g/m2和顺铂 (P) 150 mg/m2 (CEP)，以3天的时间表施用，然后是rhG-CSF，300微克每天一次，从第5天开始 (化疗结束后36小时)。根据临床需要重复循环多达三次。第一个疗程后，血液学恢复迅速而完整，没有记录的感染，也没有观察到相关的髓外毒性。10名患者中有8名接受了毒性相对较低的第二疗程，其中3名接受了第三疗程。我们得出的结论是，在表现良好的癌症患者中，通过简单的生长因子支持，可以安全甚至反复地进行CEP治疗。

BACKGROUND & AIMS: :The human iodotyrosine dehalogenase 1 (DEHAL1) gene is composed of six exons. Two isoforms (DEHAL1 and DEHAL1B) have been published in GenBank, both of which have a nitroreductase domain and arise from differential splicing in exon 5. We recently showed that the DEHAL1 isoform is a transmembrane protein that efficiently catalyzes the NADPH-dependent deiodination of mono (L-MIT) and diiodotyrosine (L-DIT) in human embryonic kidney-293 (HEK293) cells. In the present study, we establish the existence of a new transcript, DEHAL1C, in the human thyroid with a terminal exon that lacks in the DEHAL1 transcript. This exon is the complete exon 5, which is spliced in the DEHAL1B mRNA variant. These two variants encode proteins with differing C-terminal domains. Using quantitative reverse transcription polymerase chain reaction, we found that the expression of the mRNA of DEHAL1C and DEHAL1B was lower than that of DEHAL1 mRNA in the thyroid. We also observed that human DEHAL1B and DEHAL1C proteins are rapidly degraded in stably transfected HEK293 cells, unlike the DEHAL1 protein, and that exposure to the proteasome inhibitor MG132 resulted in accumulation of these proteins that was markedly time- and concentration-dependent. These findings show that the cytoplasmic tail could play a role in the stability of the protein.

背景与目标： : 人类碘酪氨酸脱卤酶1 (DEHAL1) 基因由六个外显子组成。GenBank上已发布了两种同工型 (DEHAL1和DEHAL1B)，它们都具有硝基还原酶结构域，并且是由外显子5中的差异剪接引起的。我们最近发现DEHAL1亚型是一种跨膜蛋白，可有效催化人胚肾293 (HEK293) 细胞中mono (L-MIT) 和二碘酪氨酸 (L-DIT) 的NADPH依赖性脱碘作用。在本研究中，我们确定了人类甲状腺中存在一个新的转录本DEHAL1C，其末端外显子在DEHAL1转录本中缺乏。该外显子是完整的外显子5，在DEHAL1B mRNA变体中剪接。这两个变体编码具有不同C末端结构域的蛋白质。使用定量逆转录聚合酶链反应，我们发现DEHAL1C和DEHAL1B的mRNA在甲状腺中的表达低于DEHAL1 mRNA的表达。我们还观察到，与DEHAL1蛋白不同，人DEHAL1B和DEHAL1C蛋白在稳定转染的HEK293细胞中迅速降解，并且暴露于蛋白酶体抑制剂MG132导致这些蛋白的积累明显依赖于时间和浓度。这些发现表明，细胞质尾可能在蛋白质的稳定性中起作用。

BACKGROUND & AIMS: :Angiogenesis is a crucial step in many pathologies, including tumor growth and metastasis. Here, we show that tilted peptides exert antiangiogenic activity. Tilted (or oblique-oriented) peptides are short peptides known to destabilize membranes and lipid cores and characterized by an asymmetric distribution of hydrophobic residues along the axis when helical. We have previously shown that 16-kDa fragments of the human prolactin/growth hormone (PRL/GH) family members are potent angiogenesis inhibitors. Here, we demonstrate that all these fragments possess a 14-aa sequence having the characteristics of a tilted peptide. The tilted peptides of human prolactin and human growth hormone induce endothelial cell apoptosis, inhibit endothelial cell proliferation, and inhibit capillary formation both in vitro and in vivo. These antiangiogenic effects are abolished when the peptides' hydrophobicity gradient is altered by mutation. We further demonstrate that the well known tilted peptides of simian immunodeficiency virus gp32 and Alzheimer's beta-amyloid peptide are also angiogenesis inhibitors. Taken together, these results point to a potential new role for tilted peptides in regulating angiogenesis.

背景与目标： 血管生成是许多病理的关键步骤，包括肿瘤的生长和转移。在这里，我们显示倾斜肽具有抗血管生成活性。倾斜 (或倾斜定向) 肽是短肽，已知会破坏膜和脂质核的稳定性，其特征是螺旋时疏水残基沿轴的不对称分布。我们先前已经证明，人类催乳素/生长激素 (PRL/GH) 家族成员的16 kDa片段是有效的血管生成抑制剂。在这里，我们证明了所有这些片段都具有具有倾斜肽特征的14-aa序列。人催乳素和人生长激素的倾斜肽在体外和体内均诱导内皮细胞凋亡，抑制内皮细胞增殖并抑制毛细血管形成。当肽的疏水性梯度因突变而改变时，这些抗血管生成作用就会消失。我们进一步证明，猿猴免疫缺陷病毒gp32和阿尔茨海默氏 β-淀粉样肽的众所周知的倾斜肽也是血管生成抑制剂。总之，这些结果指出了倾斜肽在调节血管生成中的潜在新作用。

BACKGROUND & AIMS: :Thyroid hormone (TH) regulates such crucial biological functions as normal growth, development and metabolism of nearly all vertebrate tissues. In skeletal muscle, TH plays a critical role in regulating the function of satellite cells, the bona fide skeletal muscle stem cells. Deiodinases (D2 and D3) have been found to modulate the expression of various TH target genes in satellite cells. Regulation of the expression and activity of the deiodinases constitutes a cell-autonomous, pre-receptor mechanism that controls crucial steps during the various phases of myogenesis. Here, we review the roles of deiodinases in skeletal muscle stem cells, particularly in muscle homeostasis and upon regeneration. We focus on the role of T3 in stem cell functions and in commitment towards lineage progression. We also discuss how deiodinases might be therapeutically exploited to improve satellite-cell-mediated muscle repair in skeletal muscle disorders or injury.

背景与目标： : 甲状腺激素 (TH) 调节着几乎所有脊椎动物组织的正常生长，发育和代谢等关键的生物学功能。在骨骼肌中，TH在调节卫星细胞 (真正的骨骼肌干细胞) 的功能中起着至关重要的作用。已发现脱碘酶 (D2和D3) 调节卫星细胞中各种TH靶基因的表达。调节脱碘酶的表达和活性构成了一种细胞自主的前受体机制，该机制控制着肌发生各个阶段的关键步骤。在这里，我们回顾了脱碘酶在骨骼肌干细胞中的作用，特别是在肌肉稳态和再生中的作用。我们专注于T3在干细胞功能和对谱系进展的承诺中的作用。我们还讨论了如何在治疗上利用脱碘酶来改善骨骼肌疾病或损伤中的卫星细胞介导的肌肉修复。

BACKGROUND & AIMS: :From 1982 to 1987, 2,433 lesions of the thyroid gland in 1,796 patients were examined by fine needle aspiration (FNA). Cytopathology classified 66.91% of the aspirates as benign, 10.76% as thyroiditis, 4.89% as suspected (unspecified) neoplasia, 1.31% as positive for malignancy and 16.11% (392) as unsatisfactory. The histologic diagnoses in 257 cases were compared with cytologic diagnoses to determine the accuracy of FNA cytology of thyroid lesions, yielding a sensitivity of 71.43%, a specificity of 100% and an accuracy of 95.09%. This data strongly supports thyroid FNA as an important preoperative diagnostic tool. Follicular carcinomas were difficult to cytologically differentiate from nonmalignant follicular neoplasms, and papillary thyroid carcinomas less than 2 cm in diameter in elderly patients were frequently misdiagnosed or diagnosed only as "suspect lesion."

背景与目标： : 从1982个1987年中，通过细针穿刺 (FNA) 检查了1,796例患者的2,433个甲状腺病变。细胞病理学将66.91% 抽吸物分类为良性，10.76% 为甲状腺炎，4.89% 为疑似 (未指定) 肿瘤，1.31% 为恶性肿瘤阳性，16.11% (392) 为不满意。将257例的组织学诊断与细胞学诊断进行比较，以确定甲状腺病变的FNA细胞学检查的准确性，从而产生71.43% 的敏感性，100% 的特异性和95.09% 的准确性。该数据强烈支持甲状腺FNA作为重要的术前诊断工具。滤泡癌在细胞学上很难与非恶性滤泡肿瘤区分开来，而老年患者直径小于2厘米的甲状腺乳头状癌经常被误诊或仅被诊断为 “可疑病变”。

BACKGROUND & AIMS: PURPOSE:The incidence of poor ovarian response in controlled ovarian stimulation (COH) has been reported in 9-24 % of IVF-ET cycles. Growth hormone augments the effect of gonadotropin on granulosa and theca cells, and plays an essential role in ovarian function, including follicular development, estrogen synthesis and oocyte maturation. The aim of this study was to assess IVF-ET cycle outcome after the addition of growth hormone in antagonist protocol in poor responders. MATERIALS AND METHODS:Eighty-two poor responder patients selected for ART enrolled the study and were randomly divided into two groups. Group I (GH/HMG/GnRHant group, n = 40) received growth hormone/gonadotropin/GnRH antagonist protocol and group II (HMG/GnRHant group, n = 42) received gonadotropin/GnRH antagonist protocol. RESULTS:The number of retrieved oocytes was significantly higher in GH/HMG/GnRHant group than HMG/GnRHant group, 6.10 ± 2.90 vs. 4.80 ± 2.40 (p = 0.035) and the number of obtained embryos was also significantly higher in GH/HMG/GnRHant group than HMG/GnRHant group, 3.7 ± 2.89 as compared to 2.7 ± 1.29 (p = 0.018). There were no significant differences between groups regarding implantation, and chemical and clinical pregnancy rates. CONCLUSION:Our study showed that co-treatment with growth hormone in antagonist protocol in patients with a history of poor response in previous IVF-ET cycles did not increase pregnancy rates.

背景与目标：

BACKGROUND & AIMS: :T cell regulation of the generation of thyroglobulin plaque-forming cells (Tg PFC) and protein A plaque-forming cells (Prot A PFC) was investigated using lymphocytes from patients with autoimmune thyroid disease. T and B cell mixed cultures (T-B MC) were carried out without mitogenic or antigenic stimulation to identify physiological T cell effects in the system. Tg PFC were found in 8 (44%) of 18 patients who had high titers of thyroglobulin antibody in their sera. Tg-specific and nonspecific immunoregulation by T cells from patients and normal subjects was studied using B cells from these eight patients in the T-B MC system. Remarkably lower values of Tg PFC induction compared to Prot A PFC induction were found after T cell addition. Normal T cells inhibited Tg PFC induction, but patient T cells did not, while the same extent of helper effects were found on Prot A PFC induction by the addition of patient and normal T cells. Irradiation (1500 rads) of T cells from patients and normal subjects significantly enhanced both TgPFC and Prot A PFC induction. Thus, Tg-specific suppressor T cells are present in all normal subjects as part of the radiosensitive suppressor T cell subset. The increase in Tg-PFC caused by irradiation-induced inhibition of Tg-specific suppressor T cell function was significantly greater in normal subjects than in patients. Histamine type 2 receptor-bearing T cells inhibited Prot A PFC induction, but not Tg PFC induction, in the autologous T-B MC system. No Tg PFC were induced from normal B cells in any combination with untreated T cells, irradiated T cells, or histamine type 2 receptor-negative T cells from patients or normal subjects. These data indicate that in vitro Tg-specific T cell regulation can be studied in the T-B MC system by using B cells from patients with autoimmune thyroid disease with high Tg antibody titers in their sera. Tg-specific suppressor T cells appear to be present in all individuals and to be involved in the regulation of Tg antibody production. The lower activity of Tg-specific suppressor T cells in patients compared to that in normal subjects may be related to Tg antibody production in vivo. This abnormality, however, is heterogeneous and is not a complete but, rather, is a relative defect of Tg-specific suppressor T cells.

背景与目标： : 使用自身免疫性甲状腺疾病患者的淋巴细胞研究了甲状腺球蛋白斑块形成细胞 (Tg PFC) 和蛋白A斑块形成细胞 (Prot A PFC) 生成的T细胞调节。在没有促有丝分裂或抗原刺激的情况下进行T细胞和b细胞混合培养 (t-b MC)，以鉴定系统中的生理T细胞作用。在18例血清中甲状腺球蛋白抗体滴度较高的患者中，有8例 (44% 例) 发现了Tg PFC。在t-b MC系统中，使用这八名患者的b细胞研究了患者和正常受试者的T细胞对Tg的特异性和非特异性免疫调节。添加T细胞后，与Prot A PFC诱导相比，Tg PFC诱导值明显降低。正常T细胞抑制Tg PFC诱导，但患者T细胞不抑制，而通过添加患者和正常T细胞对Prot A PFC诱导发现了相同程度的辅助作用。来自患者和正常受试者的T细胞的照射 (1500 rads) 显着增强了TgPFC和Prot A PFC的诱导。因此，Tg特异性抑制T细胞作为放射敏感性抑制T细胞亚群的一部分存在于所有正常受试者中。在正常受试者中，由辐射诱导的Tg特异性抑制T细胞功能抑制引起的tg-pfc的增加明显大于患者。在自体t-b MC系统中，带有组胺2型受体的T细胞抑制Prot A PFC诱导，但不抑制Tg PFC诱导。正常b细胞与未经治疗的T细胞，辐照的T细胞或来自患者或正常受试者的组胺2型受体阴性T细胞的任何组合均未诱导Tg PFC。这些数据表明，可以使用来自血清中Tg抗体滴度较高的自身免疫性甲状腺疾病患者的b细胞，在t-b MC系统中研究体外Tg特异性T细胞调控。Tg特异性抑制T细胞似乎存在于所有个体中，并参与Tg抗体产生的调节。与正常受试者相比，患者中Tg特异性抑制T细胞的活性较低可能与体内Tg抗体的产生有关。然而，这种异常是异质的，不是完整的，而是Tg特异性抑制T细胞的相对缺陷。

BACKGROUND & AIMS: :Thyroid neoplasms encompass a variety of lesions that range from benign adenomas to malignancies. These latter can be well-differentiated, poorly differentiated or undifferentiated (anaplastic) carcinomas. More than 95% of thyroid cancers are derived from thyroid follicular cells, while 2-3% (medullary thyroid cancers, MTC) originate from calcitonin producing C-cells. Over the last decade, investigators have developed a clearer understanding of genetic alterations underlying thyroid carcinogenesis. A number of point mutations and translocations are involved, not only in its tumorigenesis, but also as have potential use as diagnostic and prognostic indicators and therapeutic targets. Many occur in genes for several important signaling pathways, in particular the mitogen-activated protein kinase (MAPK) pathway. Sporadic (isolated) lesions account for 75% of MTC cases, while inherited MTC, often in association with multiple endocrine neoplasia (MEN) type 2A and 2B syndromes, constitute the remainder. However, non-MEN familial MTC may also occur. Advances in genetic testing have revolutionized the management of MTC, with prospects of genetic screening, testing and early prophylactic thyroidectomy. Ethical concerns of these advances are addressed.

背景与目标：