Co-ordinate regulation of the cystic fibrosis and multidrug resistance genes in cystic fibrosis knockout mice

The cystic fibrosis (Cftr and multidrug resistance (Mdr1) genes encode structurally similar proteins which are members of the ABC transporter superfamily. These genes exhibit complementary patterns of expression in vivo, suggesting that the regulation of their expression may be co- ordinated. We have tested this hypothesis in vivo by examining Cftr and Mdr1 expression in cystic fibrosis knockout transgenic mice (Cftr(tm1CAM)). Cftr mRNA expression in Cftr(tm1CAM)/Cftr(tm1CAM) mice was 4-fold reduced in the intestine, as compared with littermate wild- type mice. All other Cftr(tm1CAM)/Cftr(tm1CAM) mouse tissues examined showed similar reductions in Cftr expression. In contrast, we observed a 4-fold increase in Mdr1 mRNA expression in the intestines of neonatal and 3- to 4-week-old Cftr(tm1CAM)/Cftr(tm1CAM) mice, as compared with age-matched +/+ mice, and an intermediate level of Mdr1 mRNA in heterozygous Cftr(tm1CAM) mice. In 10-week-old, Cftr(tm1CAM)/Cftr(tm1CAM) mice and in contrast to the younger mice, Mdr1 mRNA expression was reduced, by 3-fold. The expression of two control genes, Pgk-1 and Mdr2, was similar in all genotypes, suggesting that the changes in Mdr1 mRNA levels observed in the Cftr(tm1CAM)/Cftr(tm1CAM) mice are specific to the loss of Cftr expression and/or function. These data provide further evidence supporting the hypothesis that the regulation Cftr and Mdr1 expression is co-ordinated in vivo, and that this co-ordinate regulation is influenced by temporal factors.      

Pneumocystis carinii pneumonia in vertically acquired HIV infection in the British Isles

In order to review the clinical course, laboratory findings, and outcome of children with vertically acquired HIV infection and Pneumocystis carinii pneumonia, questionnaires were sent to paediatricians in the British Isles who had reported P carinii pneumonia and HIV infection through the British Paediatric Surveillance Unit (BPSU). Paediatric reports from the BPSU are linked to reports of pregnancies in HIV positive women and laboratory reports. P carinii pneumonia was the most frequently reported AIDS indicator disease at AIDS diagnosis, occurring in 22/56 (40%) children born in the British Isles; in a further two children P carinii pneumonia occurred after another AIDS indicator disease. The median age at P carinii pneumonia diagnosis was 4.1 (1.4-27.3) months and in 48% it occurred with other AIDS indicator diseases. Despite intensive treatment the three month survival was only 38%. The nine children surviving P carinii pneumonia subsequently developed further AIDS indicator diseases, in particular HIV encephalopathy and four have since died. P carinii pneumonia was present at AIDS diagnosis in 65% of children developing AIDS in the first year of life and caused 82% of infant deaths. Most children were not known to be at risk of HIV until they presented with P carinii pneumonia. Children with HIV infection develop P carinii pneumonia at an early age and have a poor outcome. Increased awareness of the condition is required to initiate early treatment. Prevention may be a compelling incentive for screening in pregnancy, but further study is required to quantify the risks and benefits of initiating early P carinii pneumonia prophylaxis as well as the impact this might have on life expectancy.     

Endometrial protein PP14 and CA-125 in recurrent miscarriage patients; correlation with pregnancy outcome

The concentrations of endometrial proteins PP14 and CA-125 were measured in uterine flushings taken on days LH+10 and LH+12 (10 and 12 days after luteinizing hormone surge) of the menstrual cycle from 15 normal, fertile women and 49 women who suffered recurrent miscarriage. The concentration of PP14 was significantly lower in the flushings from the recurrent miscarriage patients than in those from fertile controls on both day LH+10 (median: 1300, range: 3-10 300 ng/ml versus median: 13 933, range: 2174-40 404 ng/ml; P < 0.01) and LH+12 (median: 1560, range: 820-12 100 ng/ml versus median: 14 047, range 1402-62 108 ng/ml; P < 0.05). Similarly concentrations of CA-125 were significantly lower in flushings from recurrent miscarriage women compared to controls on both day LH + 10 (median: 1555, range: 47-6710 U/ml versus median: 6385.5, range 2884-27 731 U/ml, P < 0.01) and LH+12 (median: 2892, range: 956-9974 U/ml versus median: 7127.5, range: 1591-21 343 U/ml; P < 0.05). In contrast there was no significant difference in the concentration of PP14 in plasma samples taken on the same days as the flushings from recurrent miscarriage patients and fertile controls. The concentrations of PP14 in uterine flushings obtained on day LH + 10 or LH + 12 from recurrent miscarriage women during a pre-pregnancy investigative cycle were significantly lower (P < 0.05) in patients who went on to miscarry (median: 1000, range: 9-2900 ng/ml) than those who went on to have a live birth (median: 1440, range: 4-12 100 ng/ml) during a subsequent pregnancy. In contrast there was no significant difference in uterine CA-125 or plasma PP14 concentrations between these two groups of recurrent miscarriage patients. The results suggest that measurements of uterine PP14 and CA-125 may be useful in the assessment of endometrial development in recurrent miscarriage patients and suggest the importance of PP14 in preparing the endometrium for embryo implantation. In addition pre-pregnancy uterine PP14 measurements may be useful in predicting subsequent pregnancy outcome.      

Co-ligation of alpha4beta1 integrin and TCR rescues human thymocytes from steroid-induced apoptosis

Maturation of thymocytes represents a sequence of events during which thymocytes expressing TCR with moderate avidity for self antigen/MHC are positively selected, whereas those with high or insufficient TCR avidity die. Glucocorticoids are produced intrathymically and can contribute to apoptosis of unselected thymocytes. Thymocytes differentiate in a close contact with epithelial cells, expressing vascular adhesion molecule-1 (VCAM-1) and secreting glucocorticoids, with bone marrow-derived macrophages, and with extracellular matrix containing fibronectin (FN) and collagen. Their contact with FN is mediated by alpha4beta1 and alpha5beta1 integrins. We examined the contribution of TCR and integrin signaling to the survival of thymocytes from dexamethasone (Dex)-induced apoptosis. We demonstrate that FN and VCAM-1 (both of which bind alpha4beta1 integrin), but not collagen, considerably augment TCR-mediated protection of thymocytes from Dex-induced apoptosis. This 'survival' signal is transduced through the alphabeta1, but not through the alpha5beta1 integrin. The observed protection from Dex-induced apoptosis correlated with an increase in bcl-2 protein levels. FN-alpha4beta1 and VCAM-1-alpha4beta1 engagement induced up-regulation bcl-2 protein, while alpha5beta1 binding to FN induced a negative signal that was blocked by anti- alpha5beta1 antibody. These data suggest that alpha4beta1 integrin may contribute to protection of thymocytes with moderate avidity TCR from glucocorticoid-induced death during intrathymic maturation.      

Pathological and molecular characterization of avian malaria in captive Magellanic penguins (Spheniscus magellanicus) in South America

Avian malaria is a mosquito-borne disease that affects multiple avian species and is caused by protozoans of the genus Plasmodium. An avian malaria infection caused by Plasmodium sp. in Magellanic penguins (Spheniscus magellanicus) with high mortality is described in a zoo in Southern Brazil. Clinically, three birds presented signs of inappetence, anorexia, pale mucosa, dyspnea, and opisthotonus, with death in a clinical course of 5–8 h. At the necropsy, all birds exhibited pale mucosa, marked splenomegaly and hepatomegaly, in addition to moderate leptomeningeal blood vessels ingurgitation in the brain. Microscopically, multiple exoerythrocytic meronts were observed in the cytoplasm of endothelial cells in the spleen, liver, heart, lungs, brain, kidneys, and pancreas. The spleen had a multifocal perivascular inflammatory infiltrate of lymphocytes, plasma cells, and macrophages, which also exhibited hemosiderosis and erythrophagocytosis. The liver had a multifocal periportal inflammatory infiltrate of lymphocytes, macrophages, and plasma cells, in addition to marked hemosiderosis in the hepatic sinusoids. Fragments of spleen, liver, brain, skeletal muscle, and lung were tested by the polymerase chain reaction technique for the detection of a fragment of the cytochrome B gene from haemosporidians, which resulted positive for Plasmodium spp. After sequencing, the samples were phylogenetically associated to Plasmodium sp. detected in Turdus albicollis (KU562808) in Brazil and matched to the lineage TURALB01 previously detected in T. albicollis. Avian malaria infections caused by Plasmodium sp. of lineage TURALB01 may occur in S. magellanicus with high mortality, and, thus, it is essential to detect and characterize the agent involved to obtain the differential diagnosis of the condition.

     

Vertebral and carotid artery anomalies in patients with aberrant right subclavian arteries

Background There is little published evidence regarding the patterns and prevalence of vertebral artery (VA) and common carotid artery (CCA) anomalies in patients with an aberrant right subclavian artery (ARSCA). Objective To study the patterns and prevalence of VA and CCA anomalies in patients with ARSCA. Materials and methods In a 2-year period we reviewed the children referred with suspected vascular ring who had undergone multidetector-row CT. Patients with ARSCA were reviewed for VA and CCA patterns and their prevalence and relevance were calculated. Results In total, 102 patients with ARSCA were identified. VA anomalies were present in 16 patients (15.7%), and CCA anomalies (common carotid trunk) in 21 patients (20.6%). In some patients with VA anomalies, the right VA arose from the right CCA and in some the left VA arose from the aortic arch. When the left VA arose from the aortic arch it was situated between the left CCA and the left SCA or between the left SCA and the ARSCA. Conclusion If neurointerventionalists understand these potential anomalies and their prevalence, time and contrast medium could be saved when catheterizing the VA and CCA in patients with ARSCA.     

Sex differences in risk factors for coronary heart disease: a study in a Brazilian population

Background  

In Brazil coronary heart disease (CHD) constitutes the most important cause of death in both sexes in all the regions of the country and interestingly, the difference between the sexes in the CHD mortality rates is one of the smallest in the world because of high rates among women. Since a question has been raised about whether or how the incidence of several CHD risk factors differs between the sexes in Brazil the prevalence of various risk factors for CHD such as high blood cholesterol, diabetes mellitus, hypertension, obesity, sedentary lifestyle and cigarette smoking was compared between the sexes in a Brazilian population; also the relationships between blood cholesterol and the other risk factors were evaluated.     

3D mesoporous structure assembled from monoclinic M-phase VO2 nanoflakes with enhanced thermochromic performance

Monoclinic M-phase VO₂ is a promising candidate for thermochromic materials due to its abrupt change in the near infrared (NIR) transmittance along with the metal-to-insulator transition (MIT) at a critical temperature ∼68 °C. However, low luminous transmittance (T_lum), poor solar energy modulation ability (ΔT_sol), and high phase transition temperature (T_c) can limit the application of VO₂ for smart windows. To overcome these limitations, 3D mesoporous structure can be employed in VO₂ films. Herein, 3D mesoporous structures assembled from monoclinic M-phase VO₂ nanoflakes with a pore size of about 2–10 nm were synthesized by a hydrothermal method using Ensete ventricosum fiber (EF) as a template followed by calcination at 450 °C. The prepared film exhibited excellent thermochromic performance with balanced T_lum = 67.3%, ΔT_sol = 12.5%, and lowering T_c to 63.15 °C. This is because the 3D mesoporous structure can offer the uniform dispersion of VO₂ nanoflakes in the film to enhance T_lum, ensure sufficient VO₂ nanoflakes in the film for high ΔT_sol and lower T_c. Therefore, this work can provide a green approach to synthesize 3D mesoporous structures assembled from monoclinic M-phase VO₂ nanoflakes and promote their application in smart windows.

Herein, 3D mesoporous structures assembled from monoclinic M-phase VO₂ nanoflakes were successfully synthesized for enhanced thermochromic performance.     

护士生注射练习发生晕厥原因与对策

1临床资料 1998-03／2002-06参与注射练习的护士生336名,均为女性,发生晕厥15例,发生率4．5％;其中3例发生在注射过程中,余12例发生在注射后2min内．静脉注射练习过程中发生晕厥2例,肌肉注射练习过程中、后发生晕厥者分别为3例和10例;年龄19～21（平均20．3）岁．均排除癫痫、癔病等器质性疾病．静脉注射练习用药为250g／L葡萄糖注射液20mL,肌肉注射练习用药为维生素B12250μg,均在有效期内,且无混浊、变质等不良情况．晕厥原因有：