Gestational diabetes mellitus (class A): A human teratogen?

Between January 1, 1982 and December 31, 1992 we evaluated 200 children of mothers with pregestational or gestational diabetes mellitus through the University of South Florida Genetics/Dysmorphology Clinics. They were a portion of the 22,100 families seen during that period. Pregnant women with diabetes mellitus were not part of this study. One hundred and fifty-two of the 200 were offspring of mothers with gestational diabetes (classes A₁ and A₂). Class B₁ was not encountered as a subclass of gestational diabetes in this series. Twenty-four of the 152 did not have anomalies. Forty-one of the 152 had another primary diagnosis to account for their malformations. Eighty-seven of the 152 had a constellation of anomalies or solitary structural defects as seen in diabetic embryopathy. Chromosomal, monogenic, and other teratogenic causes were excluded. The observed phenotypes matched those seen in offspring of mothers with diabetes mellitus classes B₂ to T. They also corroborated the animal studies, indicating that the embryopathy of gestational diabetes has a pathogenesis similar to that in classes B₂ to T, and recent epidemiological studies showing a statistically significant increase of anomalies as in diabetic embryopathy in the offspring of gestational diabetes mothers. As per established obstetric practice the testing for gestational diabetes was after gestation 16 weeks. Thus, it was impossible to prove that the anomalies of the 87 propositi were due to gestational diabetes. However, the anomalies occurred during organogenesis as in the other diabetic classes, and inferred that gestational diabetes is a human teratogen. If so, common “idiopathic” malformations may be actually caused by undiagnosed maternal gestational diabetes. Am. J. Med. Genet. 83:402–408, 1999. © 1999 Wiley-Liss, Inc.     

PC—1500(A)中医专家系统

本专家系统的特色是通过硬件扩容,采用信息压缩存贮技术和独特的知识表示方法等多种途径,在价格低廉、便于携带的JPC—1500(A)袖珍计算机上开发出实用中医专家系统。其主要特点、功能如下。 1.能进行多病域中医诊疗。在运用该系统诊疗时,不需要使用外存磁带机等其他辅助设备,也不需要更换软件,便能诊疗内、妇、眼科的多种疾病。 2.能较细致、准确地模拟中医专家的辨证论治的思维过程,人机总符合率在99％     

A型双向超声诊断仪(一)

概述 一、临床诊断对仪器的要求 超声诊断仪中,A型仪器是首先问世的。电路和元器件都较易实现,造价也较低。但是,从A型超声回声图判断人体内脏的病变,要求操作者具有较多的临床经验。成批生产的A型     

环孢素A研究的新进展(文献综述)

<正> 环孢素 A(Cyclosporin A,CsA)是一种结构为环状11肽化合物。原先是在从多孢木霉菌和柱孢霉菌两种真菌中筛选具有抗菌作用的药物时偶然发现的。最初发现CsA在弗氏佐剂诱导的关节炎中具有和保泰松相似的抗炎作用,后来发现CsA具有强的免疫抑制效应,而且没有明显的骨髓毒性。这就使许多学者从研究其抗炎作用转移到重点研究其免疫抑制作用及其抗移植排斥作用。对     

抗肉毒神经毒素A(BoNT/A)单克隆抗体的制备与鉴定

目的 :制备抗肉毒毒素A(BoNT/A)的单克隆抗体 (mAb)。方法 :用纯化的重组BoNT/A Hc片段免疫BALB/c小鼠 ,取其脾细胞与骨髓瘤Sp2 /0融合 ,经间接ELISA筛选和克隆化制备杂交瘤细胞系 ,及Western免疫印迹分析等方法对mAb进行特异性鉴定。结果 :获得 3株杂交瘤细胞株 :命名为4A8、2F7和 4F2 ,IgG亚类鉴定均为IgG1,腹水mAb的效价在 1× 10 -4～ 1× 10 -6之间。其中 ,4A8和 4F2能稳定分泌抗BoNT AmAb,并可特异性地识别重组BoNT/A和天然BoNT/A ,特别是 4A8可保护小鼠抵抗 10LD50 BoNT/A的攻击。结论 :成功地制备 3株特异性抗BoNT/AmAb ,并有 1株属于中和性mAb ,为BoNT/A的检测和肉毒中毒的临床治疗奠定了基础     

维生素A酸(视黄酸)的致畸作用

视黄酸是一种维生素的代谢产物,具有部份维生素A生理作用的生物活性物质。视黄酸与维生素A不同,在体内半衰期短,正常状态在血清中不能检出。注射给药,血清中的半衰期为16～20小时,投药4～5天后在血清中不能被检出,因此生效快,同时其作用消失也快。适应症:对重症的囊状痤疮,慢性皮炎等,维生素A可能具有使上皮细胞恢复正常     

A型双向超声诊断仪常见故障修理(二)

本文介绍了A型双向超声诊断仪的工作原理。对其容易发生的故障,指出了常见的原因。文中附有故障波形图。     

A New Species of Gynura Cass. (Compositae)

Gynura medica Y.K.Yang et J.K.Wu sp.nov.-Gynura miraculoa Y.K.Yang et J.K.Wu sp.nov.in sched.Haec species G.divaricatae(L.)DC et G.nepalensi DC similis ab illa e caule valde ramosi,foliis subtusglaucis niveis,lateri-nervis 8-12-jugatis,petiolis basi haud aurielis,phyllis involucri extra puberulis etpubescentibus 3-5-nervis,acheniis 6-9-gonis bene differt.Ab hac eaule,ramis.petiolis et foliis utroque albo-     

PC—1500(A)中医专家系统构造工具

本专家系统工具有以下主要特点和功能。 1.其显著特点是在经过扩容后的PC—1500(A)袖珍计算机上实现。也不需要使用外存磁带机和其他硬、软件设备。运用BASIC语言和机器语言结合编程。 2.利用本专家系统工具可以构造多病域中医专家系统,运行一个软件可以诊疗多     

腺苷A3受体(A3AR)在失血性休克血管反应性调节中的作用

目的： 阻力血管对血管活性物质反应性的降低是决定创伤休克发生、发展及预后的重要因素。腺苷是机体遭受创伤、缺氧时大量释放的重要内源性调质,并通过相应受体发挥作用。本研究拟观察腺苷A3受体(A3AR)在失血性休克大鼠肠系膜上动脉的表达变化情况及其与休克血管反应性变化间的关系,初步探讨A3AR是否参与对休克血管反应性的调节。方法：参照以往的工作基础,建立大鼠失血性休克(40 mmHg)模型;大鼠肠系膜上动脉对缩血管物质去甲肾上腺素(NE)诱导的收缩反应性采用离体小血管张力测定仪检测;A3AR的蛋白及mRNA表达变化情况分别采用Western blotting及RT-PCR进行检测。结果：结果显示,在大鼠失血性休克后0-4 h,其肠系膜上动脉1-2级分支血管对由NE诱导的收缩反应性呈现“双向性”变化;A3AR mRNA表达随休克时间的延长呈逐渐降低的趋势,但无显著差异;而肠系膜上动脉血管平滑肌A3AR的蛋白表达在休克后即刻呈增加趋势,随着休克时间的延长,其表达逐渐下降,尤其以休克后4h的表达下降最为明显;此外,A3AR激动剂可部分恢复休克2 h大鼠肠系膜上动脉对NE的收缩反应性,且该作用可被A3AR阻断剂MRS1523所拮抗。结论：A3AR参与失血性休克血管低反应性的形成,在失血性休克后激动A3AR受体可保护血管功能,部分恢复失血性休克后大鼠阻力血管对NE的收缩反应性。     

雌二醇对去卵巢大鼠下丘脑5-HT_(1A)和5-HT_(2A)受体亚型mRNA表达的影响

观察17β-雌二醇(17β-estradioI,E2)对去卵巢大鼠下丘脑5-HT1A和5-HT2A受体mRNA表达的影响的时间效应。实验动物分为假去卵巢对照组(OVX+S组)和去卵巢组(OVX)。去卵巢组大鼠又分为雌激素处理组(OVX+E+组)和无雌激素处理组(OVX+E-组),分别在处理后3、6、9和12 d时,采用反转录-聚合酶链式反应(RT-PCR)方法观察5-HT1A和5-HT2A受体mR-NA在大鼠下丘脑的表达。结果显示:5-HT1A和5-HT2A受体mRNA在所有大鼠下丘脑均有表达;5-HT1A受体mRNA在3、6和9 d的OVX+E-组大鼠下丘脑的表达水平明显高于同时间点的OVX-E+组,而5-HT2A受体mRNA在6、9和12 d的OVX+E-组下丘脑的表达量也显著高于同时间点的OVX+E+组。本文结果表明去卵巢后大鼠下丘脑5-HT1A和5-HT2A受体亚型mRNA表达水平升高,17β-雌二醇可下调两种受体的表达。     

Apparent cyclophosphamide (cytoxan) embryopathy: A distinct phenotype?

Cyclophosphamide (CP) is an alkylating agent widely used in treating cancer and autoimmune disease. CP is classified as a pregnancy risk factor D drug and is teratogenic in animals, but population studies have not conclusively demonstrated teratogenicity in humans. Six isolated reports of prenatally exposed infants with various congenital anomalies exist, but to date no specific phenotype has been delineated. The purpose of this report is to document a new case of in utero CP exposure with multiple congenital anomalies and to establish an apparent CP embryopathy phenotype. The mother had systemic lupus erythematosus and cyclophosphamide exposure in the first trimester. She also took nifedipine, atenolol, clonidine, prednisone, aspirin, and potassium chloride throughout pregnancy. The infant had growth retardation and multiple anomalies including microbrachycephaly, coronal craniosynostosis, hypotelorism, shallow orbits, proptosis, blepharophimosis, small, abnormal ears, unilateral preauricular pit, broad, flat nasal bridge, microstomia, high-arched palate, micrognathia, preaxial upper limb and postaxial lower limb defects consisting of hypoplastic thumbs, and bilateral absence of the 4th and 5th toes. Chromosomes were apparently normal. The reported cases of in utero exposure to cyclosposphamide shared the following manifestations with our patient: growth deficiency, developmental delay, craniosynostosis, blepharophimosis, flat nasal bridge, abnormal ears, and distal limb defects including hypoplastic thumbs and oligodactyly. We conclude that (a) cyclophosphamide is a human teratogen, (b) a distinct phenotype exists, and (c) the safety of CP in pregnancy is in serious question. Am. J. Med. Genet. 86:237–241, 1999. © 1999 Wiley-Liss, Inc.     

Differential Susceptibility to Experimental Allergic Encephalomyelitis (EAE) in Genetically Defined A+ and A− Rabbits

Only one out of 57 A-/ A- rabbits immunized with rat or guinea-pig myelin developed clinical signs suggestive of EAE. On the contrary, clinical signs of acute or chronic EAE were found in two thirds of the 102 A + /A+ and A + /A - rabbits immunized in the same way. About one third of the diseased animals had reversible acute EAE, another third died paralysed and the last third developed chronic progressive or relapsing EAE. Incidence and severity of EAE symptoms were positively correlated with age and no significant difference was observed between males and females.

Cellular and humoral anti-myelin responses were stronger in A⁺ than in A^? rabbits. Anti-A antibodies, on the contrary, were only detected in A ^? rabbits. The A ⁺ rabbits did not make Anti-A at any time. Anti-A antibodies increased early, in A^? rabbits, after immunization with myelin (11–30 days) and were later replaced by a low, but specific, anti-myelin response (60–90 days).

The gene responsible for the susceptibility to EAE is autosomal and dominant over resistance. This gene must be closely linked to the A locus or might be the A gene itself. The low susceptibility of A^? rabbits to the disease could be, in this last case, a consequence of the competition between the early anti-A and the normal anti-myelin immune responses, both induced by the injection of myelin.     

核受体家族4A(NR4A)与免疫细胞及相关疾病关系的研究进展

核受体家族4A(NR4A)是核受体亚家族成员,其转录活性很大程度上由其表达水平决定。NR4A参与多种信号转导通路,如核因子κB(NF-κB)通路等,调控相关靶基因的表达,在T淋巴细胞、造血干细胞、单核细胞、巨噬细胞、调节性T细胞(Treg)等免疫细胞的分化、发育中发挥重要作用。它还参与机体自身免疫耐受及免疫自稳态的形成,可以通过调节免疫细胞极化作用控制机体炎症应答的强度。NR4A基因缺失可以导致严重的自身免疫反应。此外,NR4A受体在机体代谢、免疫功能、心血管疾病、神经系统功能、炎症性疾病、恶性肿瘤中扮演重要角色。     

葡萄球菌A蛋白在免疫学技术中的应用(上)

葡萄球菌A蛋白(Staphylococcal ProteinA,简称SPA)是金黄色葡萄球菌细胞壁上的一种蛋白质,它具有以下特点:(1)能与人及多种哺乳动物血清IgG分子的Fc段发生非特异性结合;(2)SPA-IgG复合物与一般抗原抗体复合物一样,能激活补体系统;(3)抑制IgG调理素对吞噬和杀菌的促进作用;(4)导致离体豚鼠回肠产生类似过敏反应样     

1例B(A)亚型血型鉴定及分析

目的:对1例献血者ABO血型检测与初筛血型检测不符样本进行血清学及分子生物学鉴定并分析其原因。方法:纸片法初筛血型,应用PK7300血型仪进行ABO血型鉴定,试管法进行血型血清学复测ABO血型,使用测序技术对献血者ABO基因进行测序并比对测序结果。结果:纸片法血型鉴定为AB型,PK7300血型仪正反鉴定一致为B型,试管法血型检测该献血者为B(A)型,测序分析证实ABO基因型:B(A).02/O.01.02,在700位有CG杂合突变,测序结果与试管法血型血清学检测一致,证实该献血员为B(A)亚型。结论:PK7300血型仪鉴定血型存在亚型漏检,试管法ABO血型鉴定是实验室全自动血型检测方法很好的补充。     

粘多糖贮积症IV型(A亚型)一例

病例:女,2.5岁,因一年半来渐“驼背”,走路困难,手腕向尺侧弯曲于1989年3月15日来我医院就诊。患儿生后即手腕向尺侧弯曲,近一年渐加重,且一年半来渐“驼背”,走路困难,患儿智力发育尚正常,食欲一般,其它方面未见明显异常。患儿为第一胎,足月剖腹产,生后无窒息及抽风,母乳喂养,生后1个月会笑,3个月认母,4个月握物,7个月会坐,13个月走路,2岁说一般话。父母非近亲结婚,家族中无类