Actin mutations are one cause of congenital fibre type disproportion

We report three heterozygous missense mutations of the skeletal muscle alpha actin gene (ACTA1) in three unrelated cases of congenital fiber type disproportion (CFTD) from Japan and Australia. This represents the first genetic cause of CFTD to be identified and confirms that CFTD is genetically heterogeneous. The three mutations we have identified Leucine221Proline, Aspartate292Valine, and Proline332Serine are novel. They have not been found previously in any cases of nemaline, actin, intranuclear rod, or rod-core myopathy caused by mutations in ACTA1. It remains unclear why these mutations cause type 1 fiber hypotrophy but no nemaline bodies. The three mutations all lie on one face of the actin monomer on the surface swept by tropomyosin during muscle activity, which may suggest a common pathological mechanism. All three CFTD cases with ACTA1 mutations had severe congenital weakness and respiratory failure without ophthalmoplegia. There were no clinical features specific to CFTD cases with ACTA1 mutations, but the presence of normal eye movements in a severe CFTD patient may be an important clue for the presence of a mutation in ACTA1.     

Weight development over time in parous women--the SPAWN study--15 years follow-up

BACKGROUND: Weight gain is common after pregnancy. Most studies suggest that weight gain associated with a pregnancy is between 0.5 and 3.8 kg up to 2.5 y of follow-up. However, 73% of the female patients at our obesity clinic identified pregnancy as an important trigger for marked weight retention. The majority retained more than 10 kg after each pregnancy. The aim of this study was to examine long-term weight development after pregnancy in a 15 y follow-up of women who took part in the Stockholm Pregnancy And Women's Nutrition (SPAWN) study. METHOD AND SUBJECTS: The SPAWN study is a long-term follow-up study of women who delivered children in 1984-85 in Stockholm (n=2342). A total of 1423 participants (response rate=61%) completed questionnaires, which covered eating behaviour and exercise, demographic information including social situation and status and details of the pregnancy before, during and up to 1 y after pregnancy. After 15 y, these women were invited to take part in the follow-up study. Anthropometric measurements and the same questionnaire data were collected from the 563 women who participated (response rate=40%). The sample was divided into two main groups: those who were normal weight before pregnancy and remained normal weight, and those who were normal weight before pregnancy and had become overweight at 15 y follow-up. RESULTS: Those women who became overweight had a higher pre-pregnant body mass index (BMI) (22.3+/-1.5 vs 20.5+/-1.6 kg/m(2), P<0.001), gained more weight during pregnancy (16.3+/-4.3 vs 13.6+/-3.7 kg, P<0.001) and had retained more at 1 y follow-up. The women who became overweight had a steeper weight trajectory gaining more from 1 y follow-up to 15 y follow-up (11.1+/-6.5 vs 4.5+/-6.5 kg, P<0.001), with a higher BMI at 15 y follow-up of 27.5+/-2.6 vs 22.5+/-2.3 5 kg/m(2) (P<0.001). However, differences between those who became overweight and those who did not could not be explained by age, number of children and various socioeconomic factors. Features of pregnancy that did differ between the two groups were breastfeeding and smoking cessation. However, women who became overweight had lower lactation scores than women who remained normal weight. Relatively more subjects of the group that became overweight stopped smoking during pregnancy. DISCUSSION: Pregnancy is a vulnerability factor for some women to become overweight. This study attempted to identify those factors that place initially normal weight women on a steeper weight trajectory as a result of pregnancy. Demographic, behavioural, physical and psychological characteristics only partly explain the weight gain observed at 15 y follow-up. Further research is required to investigate the relative role of these characteristics in predicting postpregnancy weight development.     

Infectiousness in a cohort of brazilian dogs: why culling fails to control visceral leishmaniasis in areas of high transmission

The elimination of seropositive dogs in Brazil has been used to control zoonotic visceral leishmaniasis but with little success. To elucidate the reasons for this, the infectiousness of 50 sentinel dogs exposed to natural Leishmania chagasi infection was assessed through time by xenodiagnosis with the sandfly vector, Lutzomyia longipalpis. Eighteen (43%) of 42 infected dogs became infectious after a median of 333 days in the field (105 days after seroconversion). Seven highly infectious dogs (17%) accounted for >80% of sandfly infections. There were positive correlations between infectiousness and anti-Leishmania immunoglobulin G, parasite detection by polymerase chain reaction, and clinical disease (logistic regression, r2=0.08-0.18). The sensitivity of enzyme-linked immunosorbent assay to detect currently infectious dogs was high (96%) but lower in the latent period (<63%), and specificity was low (24%). Mathematical modeling suggests that culling programs fail because of high incidence of infection and infectiousness, the insensitivity of the diagnostic test to detect infectious dogs, and time delays between diagnosis and culling.     

氯喹对烟雾吸入伤大鼠肺细胞膜ATP酶活性和丙二醛含量的影响

目的：探讨氯喹对烟雾吸入伤大鼠肺细胞膜ＡＴＰ酶活性及丙二醛含量的影响,方法：８０只Ｗｉｓｔａｒ大鼠随机分成正常对照组,烟雾吸入伤１,３,６,１２和２４ｈ组以及氯喹治疗６ｈ和１２ｈ组,分别于各时相点活杀动物,取肺制备膜制剂,用生化比色法测定膜上Ｎａ＾＋,Ｋ＾＋－ＡＴＰ酶Ｍｇ＾２＋－ＡＴＰ酶和Ｃａ＾２＋－ＡＴＰ酶活性,用比色法测定膜上丙醛含量,并用定磷法测定膜总磷脂含量,结果：烟雾吸入伤后,肺细胞膜３