Ectopic ACTH secretion due to a bronchopulmonary carcinoid localized by somatostatin receptor scintigraphy

We present the case of a 65-year-old woman with an adrenocorticotropic hormone (ACTH) secreting bronchopulmonary carcinoid. This patient showed the typical long history of Cushing's syndrome, including hypokaliemia, impaired glucose tolerance, high levels of ACTH and -endorphin, and coproduction of other peptides. At the onset of clinical symptoms in 1979 an adrenal adenoma was suspected, and left-sided adrenalectomy was performed. The symptoms soon recurred, and the diagnosis of ACTH-dependent Cushing's syndrome was made. As no ACTH-secreting tumor was found, the right adrenal was resected, and the patient was followed up regularly. Fourteen years later chest roentgenography and computed tomography revealed a para-aortic pulmonary lesion, which was suspicious for a bronchopulmonary carcinoid. ACTH and -endorphin were excessively, pancreatic polypeptide slightly elevated at that time. The final diagnosis was made using somatostatin receptor scintigraphy which confirmed the hormonal activity of the suspicious lesion; no additional focus was found. This method turned out to be not only a useful additional localization technique but also a promising tool for characterization and staging of a suspected ACTH-producing carcinoid. The tumor was resected curatively, and the diagnosis was confirmed histologically.Abbreviations ACTH adrenocorticotropic hormone - DST dexamethasone suppression test - CRH corticotropin-releasing hormone - SRS somatostatin receptor scintigraphy - CT computed tomography - MRI magnetic resonance imaging     

The direct early diagnosis of cystic fibrosis by the detection of the deltaF508 CFTR gene mutation in a prematurely delivered boy

The suspicion of prenatal meconium ileus syndrome was raised in a pregnancy in a family with no history of cystic fibrosis because of significantly higher maternal serum alpha-fetoprotein in the 16th and 19th week of gestation, dispersed areas with increased echogenity in the fetal abdomen, slight fetal ascites in the 24th-25th weeks of gestation, decreased amniotic fluid gamma-glutamyltranspeptidase (GGT) activity and alpha-fetoprotein level in the 25th-26th weeks, and normal 46,XY karotype of the fetus. The detection of a homozygous deltaF508 cystic fibrosis transmembrane regulator (CFTR) gene mutation, by means of PCR from a small amount of white blood cells and urine sediment cells, substantiated the diagnosis of cystic fibrosis in a prematurely delivered boy in the 28th week of gestation. The repeated sweat test was unsuccessful. The autopsy examination confirmed the diagnosis of cystic fibrosis. Fetal meconium ileus syndrome was complicated by peritonitis and by formation of a meconium pseudocyst. Direct PCR typing improves postnatal diagnostic possibilities in the early neonatal period in prematurely delivered babies when the sweat test is difficult to perform.     

The final demise of Rodriguez lethal acrofacial dysostosis: A case report and review of the literature

We evaluated a newborn with acrofacial dysostosis in whom a clinical diagnosis of Nager syndrome was entertained. Radiographs revealed hypoplasia of the scapulae and bilateral humeroradial synostosis, with absent ulna on the left and hypoplastic ulna on the right. The finding of bilateral humeroradial synostosis had not been seen in cases of Nager syndrome before and we considered other diagnoses. Humeroradial synostosis has been found in three cases of acrofacial dysostosis Rodriguez type, a syndrome characterized by mandibular hypoplasia, upper and lower extremity phocomelia, and oligodactyly of the upper limbs. More recently, haploinsufficiency of the SF3B4 gene has been identified as the cause of both Nager and Rodriguez syndrome, leading many to believe that Rodriguez syndrome represents a more severe end of a Nager syndrome spectrum. An SF3B4 mutation was found in our patient, prompting a review of the previous known cases of Rodriguez syndrome, which revealed no clustering of SF3B4 mutations, and four cases of Rodriguez syndrome with mutations identical to those in cases of Nager syndrome. Rodriguez syndrome was previously thought of as a lethal acrofacial dysostosis distinct from Nager syndrome. A number of more mild cases, as well as our case, intermediate between the two phenotypes, illustrate that Rodriguez syndrome is a severe manifestation of Nager syndrome, and is not lethal with aggressive medical care.     

The impact of somatic mosaicism on bicuspid aortic valve and aortic dissection in Turner Syndrome

Somatic mosaicism is a major modifier of turner syndrome (TS) features and may be more prevalent than once thought, as new molecular techniques enable detection of tissue‐specific mosaicism. This review explores the causes of mosaicism, discusses how mosaicism may impact congenital aortic defects in TS, and summarizes molecular methods to detect mosaicism in different contexts.     

严重急性呼吸综合征患者尸解肺标本的病理改变和致病机制研究

目的研究严重急性呼吸综合征（SARS）患者尸解肺标本的病理改变和致病机制。方法观察了2003年4-7月期间死于SARS的6例患者的肺标本,并采用光镜、电镜、Masson三色染色和免疫组织化学染色方法（EnVision法）进行研究。结果肺标本的病理形态改变：（1）6例的双肺均可见到弥漫性实变病灶,肺重量明显增加;（2）6例均可见到弥漫性肺泡损伤,包括透明膜形成、肺泡腔内水肿／出血、纤维素沉积和肺泡上皮细胞脱屑,AE1／AE3免疫组织化学染色显示肺泡上皮细胞的完整性明显破坏;（3）Ⅱ型肺泡上皮细胞轻度增生,有一定异型性,细胞体积增大,胞质呈双染性和颗粒状,胞质内可见小脂肪空泡聚集（5／6）;（4）6例中有5例可见巨细胞在肺泡内浸润,巨细胞大多AEl／AE3阳性（5／6）,少数CD68阳性（2／6）;（5）组织学形态和免疫组织化学染色证实肺泡腔内和肺泡间隔内有多量巨噬细胞浸润（6／6）;（6）6例中有5例可见巨噬细胞噬红细胞象;（7）6例中有5例可见肺纤维化,包括肺泡间隔和肺间质增宽（5／6）、肺泡腔内渗出物机化（6／6）和胸膜增厚（4／6）。Masson三色染色证实胶原纤维明显增生,免疫组织化学染色显示大多数为Ⅲ型胶原。光镜和免疫组织化学染色显示5例有明显的成纤维细胞／肌纤维母细胞增生灶;（8）5例可见支气管黏膜鳞状上皮化生;（9）6例患者均可见血栓;（10）2例同时合并其他感染,1例合并细菌感染,另1例合并真菌感染。此外,电镜发现在肺泡上皮细胞和肺血管内皮细胞的胞质内有冠状病毒样颗粒。结论SARS冠状病毒直接损伤肺泡上皮细胞、巨噬细胞明显浸润和成纤维细胞／肌纤维母细胞显著增生在SARS的致病机制中起重要作用。     

Multilocular thymic cyst associated with follicular hyperplasia: clinicopathologic study of 4 resected cases

We report here 4 cases of multilocular thymic cysts (MTCs) with reactive lymphoid follicular hyperplasia. They were admitted to our hospital to examine anterior mediastinal masses demonstrated on chest computed tomographic scans. Three patients presented high-grade intermittent fever, and 2 patients were associated with Sjogren syndrome with elevated serum antinuclear antibody levels. All patients were subjected to extended thymectomy. Interestingly, their fever disappeared immediately after surgery. Histologically, the lesions were characterized by several cystic spaces separated by various thick walls with dense lymphoid tissue containing large reactive germinal centers. The inner cyst walls were lined by flattened cuboidal epithelia in some portions. Columnar epithelia with focal cilia were partially observed in 2 cases. These pathological findings led to a diagnosis of MTCs that were thought to result from cystic transformation of medullary duct derivatives by acquired inflammatory processes. The pathological findings, together with clinical courses of our cases, suggest that inflammation accompanied by autoimmune diseases may play, in part, an important role in the development of MTCs.     

Noninvasive prenatal diagnosis of chromosomal aneuploidies by isolation and analysis of fetal cells from maternal blood

The isolation and analysis of nucleated fetal cells (NFCs) from maternal blood may represent a new approach to noninvasive prenatal diagnosis. Although promising, these techniques require highly accurate separation of NFCs from nucleated cells of maternal origin; the two major problems limiting these techniques are the relative rarity of fetal cells in maternal blood and the need to establish their fetal origin. We now report a novel procedure that has allowed accurate separation of NFCs from maternal cells. The technique reported involves direct micromanipulator isolation of histochemically identified hemoglobin F‐positive nucleated cells to obtain fetal nucleated red blood cells (FNRBCs) of high yield and purity. Using this technique, followed by cell‐by‐cell multicolor fluorescence in situ hybridization (FISH) analysis of purified FNRBCs, we were able to detect some of the most common human aneuploidies (including Down syndrome, Klinefelter syndrome, and trisomy 13) in 33 pregnant women referred for amniocentesis. The procedure used, which can be completed in <72 hrs, produced complete concordance with the results of amniocentesis. We also confirm findings of prior studies suggesting that the number of FNRBCs in maternal circulation is remarkably higher in abnormal pregnancies than in normal pregnancies, especially in women carrying a fetus with trisomy 21. © 2001 Wiley‐Liss, Inc.     

Is Tourette syndrome a cause of sudden infant death syndrome and childhood obstructive sleep apnea?

The cause of sudden infant death syndrome (SIDS) is unknown. Sleep-related impairment of respiratory control and arousal are postulated; hyperdopaminergic and hyposerotonergic dysfunction may contribute to events leading to infant apnea and SIDS. Psychosocial adversity and impulsive and compulsive behaviours characterize some families of SIDS victims. Tourette syndrome (TS) is a common hereditary neurobehavioral disorder characterized by the frequent presence of impulsive and compulsive behaviors. Sleep disorders are common and include sleep apnea and abnormal arousal. Hyperdopaminergic and hyposerotonergic abnormalities are postulated to contribute to the pathophyusiology of the disorder. The following is a report of the presence of incidents of infant apnea and SIDS in families in which TS was present. In an additional TS family, a child had obstructive sleep apnea syndrome (OSAS). Results of a preliminary survey suggest that TS gene carriers are at increased risk of life-threatening apneas of infancy and that the prevalence of SIDS in such families may be 2 to 5 times the prevalence in the general population. The presence in some pedigrees of sleep apnea in children and adults suggest that in some instances disorders of sleep-related ventilatory control and arousal occurring throughout the life-span share common pathophysiological mechanisms. © 1993 Wiley-Liss, Inc.     

M1型巨噬细胞源外泌体增强卵泡膜细胞的活力

目的:探讨M1型巨噬细胞源外泌体对卵泡膜细胞活力的影响及其作用机制。方法:采用脂多糖(LPS)处理Raw264.7小鼠巨噬细胞,构建M1型巨噬细胞模型及巨噬细胞-卵泡膜细胞共培养体系。超速离心法分离巨噬细胞分泌的外泌体;通过电镜、Western blot和纳米流式检测仪鉴定外泌体。体外分离培养小鼠卵泡膜细胞,与PKH67荧光标记的外泌体共孵育,观察卵泡膜细胞摄取外泌体的情况。CCK-8法检测细胞活力,流式细胞术分析细胞周期分布,q PCR及Western blot检测细胞周期蛋白依赖性激酶抑制因子1B(CDKN1B)的表达。结果:在巨噬细胞-卵泡膜细胞共培养体系中,LPS诱导的M1型巨噬细胞通过外泌体增强卵泡膜细胞活力。电镜、Western blot及纳米流式检测结果显示,巨噬细胞源外泌体被成功分离。PKH67标记的外泌体与卵泡膜细胞共孵育实验证实卵泡膜细胞能摄取大量巨噬细胞源外泌体。这些外泌体可增强卵泡膜细胞的活力,使卵泡膜细胞G0/G1期比例下降,S期比例升高,且卵泡膜细胞CDKN1B的m RNA及蛋白相对表达量均明显低于对照组。结论:卵泡膜细胞能摄取巨噬细胞分泌的外泌体。M1型巨噬细胞源外泌体通过抑制CDKN1B的表达而增强卵泡膜细胞的活力。     

多囊卵巢综合征患者的生长分化因子9基因的突变分析

目的通过对多囊卵巢综合征（PCOS）妇女的生长分化因子9（GDF-9）基因的突变分析，探索GDF-9基因与PCOS的发病机制的关系。方法对120例PCOS患者釉80例正常对照的GDF-9基因进行聚合酶链反应（PCR）特异扩增，应用单链构象多态性（SSCP）分析和DNA测序方法检测基因突变。结果PCOS患者的GDF-9的所有外显予均未发现错义突变。结论GDF-9因子的DNA变异可能与PCOS的发病没有相关关系。研究PCOS患者的GDF-9的mRNA与蛋白表达水平与其发病的关系可能是今后的研究方向。