Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states

Familial multiple endocrine neoplasia type 1 (FMEN1) is an autosomal dominant trait characterized by tumors of the parathyroids, gastro- intestinal endocrine tissue, anterior pituitary and other tissues. We recently cloned the MEN1 gene and confirmed its identity by finding mutations in FMEN1. We have now extended our mutation analysis to 34 more unrelated FMEN1 probands and to two related states, sporadic MEN1 and familial hyperparathyroidism. There was a high prevalence of heterozygous germline MEN1 mutations in sporadic MEN1 (8/11 cases) and in FMEN1 (47/50 probands). One case of sporadic MEN1 was proven to be a new MEN1 mutation. Eight different mutations were observed more than once in FMEN1. Forty different mutations (32 FMEN1 and eight sporadic MEN1) were distributed across the MEN1 gene. Most predicted loss of function of the encoded menin protein, supporting the prediction that MEN1 is a tumor suppressor gene. No MEN1 germline mutation was found in five probands with familial hyperparathyroidism, suggesting that familial hyperparathyroidism often is caused by mutation in another gene or gene(s).      

Nitric oxide synthase activity and localization do not change in uterus and placenta during human parturition

Animal studies have suggested that nitric oxide, a smooth muscle relaxant, is a fundamental mediator in the initiation of parturition. The purpose of this study was to test the hypothesis that the onset of human labour is associated with a reduction in the activity of the enzyme nitric oxide synthase (NOS), within the uterus. Samples of myometrium, placenta, decidua and fetal membranes were collected during Caesarean section from 11 women before and 11 women after the onset of labour at term. Immunocytochemistry was used to localize each of the three isoforms of NOS (endothelial NOS, brain NOS, and inducible NOS) in each of these tissues and the intensity of staining was qualitatively assessed. NOS enzyme activity was determined in homogenates of frozen myometrium, placenta and fetal membranes (with attached decidua), by measuring conversion of radio-labelled L-arginine to L-citrulline. Each of the three isoforms of NOS was localized in each of the tissues. We found no difference in either the expression or enzyme activity of NOS in myometrium, placenta or fetal membranes before and during labour at term. These results suggest that, in contrast to animal studies, a decrease in NOS enzyme activity may not be involved in the onset of parturition at term in the human.      

教学模式改革下高校图书馆期刊阅览室工作的转变

运用走访调查和工作实践总结的方法,指出高校期刊阅览室服务存在的问题,提出高校期刊阅览室应在服务理念和方式、馆藏结构、馆员整体素质等方面都做出相应的转变,以满足教学模式改革环境下高校教学和科研对情报信息的需求。     

经阴道子宫肌瘤剔除术57例临床分析

目的:探讨经阴道子宫肌瘤剔除术的临床价值.方法:选择57例有子宫肌瘤剔除术指征的患者,行经阴道子宫肌瘤剔除术作为研究组,选取64例经腹子宫肌瘤剔除术作为对照,分析比较两组的一般资料及围手术期临床特点.结果:研究组的手术时间短于对照组(P＜0.05),术中出血与对照组比较不增加(P＞0.05),术后肛门排气时间明显短于对...     

Use of a questionnaire to identify potential blood donors at risk for infection with Trypanosoma cruzi

Trypanosoma cruzi is the protozoan parasite that causes American trypanosomiasis (Chagas' disease). Chagas' disease is endemic in Latin America. The infection is usually seen in poor people who live in rural areas in substandard housing, where they are bitten by infected reduviid bugs. Transmission also can occur by blood transfusion. Infected individuals who immigrate to the United States might donate blood if they are asymptomatic and unaware of their infection. This study evaluated the usefulness of a questionnaire for identifying T. cruzi-infected individuals among prospective blood donors who met all American Association of Blood Banks, Food and Drug Administration, and State of California criteria for donor eligibility. Seventy-two of 3492 otherwise eligible donors were disqualified because of their answers on the questionnaire. Forty-five of these 72 agreed to be tested serologically, and 2 were positive for T. cruzi antibodies. One of six autologous blood donors tested also was positive for T. cruzi antibodies. We conclude that the questionnaire selected a subgroup of Latin Americans at high risk for T. cruzi infection. The deferral of these high-risk individuals clearly reduced the risk of transmission of T. cruzi by transfusion, without intolerably decreasing the supply of donated blood.     

Outcome in children from cryopreserved embryos

A cohort of 91 children from cryopreserved embryos and 83 control children who were conceived normally had their development assessed using the Griffiths's scales of mental development. The controls (81 singletons and two twins) of a similar age, sex, and social class were selected from siblings, cousins, and peers of the cryopreserved embryo group (68 singleton, 20 twins, and three triplets). Children from cryopreserved embryos had a lower mean birth weight and mean gestational age and a higher proportion were born by caesarean section. One child from the cryopreserved embryo group had Down's syndrome, three had squints, and four had conductive hearing loss while in the control children, six had squints, and nine had conductive hearing loss. In both groups, including the child with Down's syndrome, the mean Griffiths's quotient was greater than the standard 100. In the children from cryopreserved embryos, the singleton and multiple birth subgroups had statistically similar assessment results. The mean (SD) Griffiths's quotient was 105.69 (13.55) in children from cryopreserved embryos and 108.18 (9.80) in controls at a chronological age of 25.08 (12.86) and 29.19 (14.65) months respectively. Overall, the development in children from cryopreserved embryos did not cause concern though formal testing had highlighted small differences compared with other children conceived normally and of a similar social class.     

De novo mutations (GAG deletion) in the DYT1 gene in two non-Jewish patients with early-onset dystonia

The DYT1 gene recently has been cloned and shown to contain a three nucleotide (GAG) deletion responsible for most cases of autosomal dominant early-onset torsion dystonia. This deletion results in the loss of one of a pair of glutamic acids in a conserved region of a novel ATP-binding protein (torsinA). Previous haplotype analysis revealed that this same deletion had arisen at least two different times in history, suggesting independent mutational events. This deletion is the only sequence change found thus far to be associated uniquely with the disease status, regardless of ethnic origin. Here we describe two patients with typical early-onset torsion dystonia of Swiss-Mennonite and non-Jewish Russian origin, respectively, that both carry this same mutation as a de novo GAG deletion. This finding proves that this 3 bp deletion in the DYT1 gene is indeed a mutation that causes early-onset torsion dystonia. The DYT1 mutation is one of the rare examples of the same recurrent mutation causing a dominantly inherited condition. The sequence surrounding the GAG deletion contains an imperfect 24 bp tandem repeat, suggesting a possible mechanism for the high frequency of this mutation.