Polygenic regulation of antibody synthesis to sheep erythrocytes in the mouse: a genetic analysis

Selective breeding for the character “agglutinin production to heterologous erythrocytes” was performed on random-bred populations of albino mice. Two types of selection were carried out: Selection I: the first 6 generations were immunized with sheep erythrocytes (SE), then SE and pigeon erythrocytes (PE) were alternated at each generation to avoid the interference of maternal antibody. Selection II: all generations were immunized with SE 60–70 days after weaning in order to eliminate the maternal antibody. Both were selected for the character agglutinin titer 14 days after immunization using an optimal dose of erythrocytes. Selection I. The mean response to SE of the foundation population was 7.36 ± 1.60. The selection limit was attained between the 15th and the 20th generation. The F₂₀?F₃₀were considered as homozygous for the character investigated. The mean SE agglutinin titers were 9.15 (1/2820) in the high responder line and 2 (1/20) in the low responder line. This corresponds to 140-fold interline difference in agglutinin titers. SE agglutinins determined in F₁ hybrids, F₂ hybrids and backcrosses obtained from F₂₃ ? F₂₉ demonstrated incomplete dominance of high responsiveness (23–29%). The inbreeding coefficient produced by close colony breeding was 0.55 in high and 0.71 in low responders at the 20th generation when both lines were homozygous with respect to agglutinin synthesis. Selection II. The mean response of the foundation population to SE was 7.79 ± 1.56. The selection limit was attained in F₁₄?F₁₇ generations that were considered homozygous for the character investigated. The mean SE agglutinin titer was 9.2 (1/2900) in high responders and 2.8 (1/35) in low responders, which is an 83-fold interline difference in agglutinin titers. The results of both selections indicate that the character agglutinin synthesis is subject to polygenic regulation. The heritability (h²) of this character was estimated to be between 0.18 and 0.36 (range between the extreme values of Selections I and II). The attempt to evaluate approximately the number of “loci” is compatible with the hypothesis that a group of about 10 loci regulates the quantitative antibody response. The sources of errors of this evaluation and the significance of the term “loci” are discussed.     

Stimulation of an intracranial trigeminally-innervated structure selectively increases cerebral blood flow

The cranial circulation, both extracerebral and cerebral, is innervated by fibers from the trigeminal nerve. This system is known as the trigeminovascular system. The large venous sinuses and dura mater are pain-sensitive and are innervated primarily by branches of the ophthalmic division of the trigeminal nerve. Studies were conducted in the α-chloralose anaesthetised cat to examine bulk carotid and cerebral blood flow responses to electrical stimulation of the trigeminal ganglion and superior sagittal sinus. Bulk carotid blood flow was measured using an ultrasonic flow probe and meter applied to the common carotid artery while cerebral blood flow was measured using laser Doppler flowmetry. Vascular resistance was calculated using simultaneously collected blood pressure data. Stimulation of the trigeminal ganglion resulted in a frequency-dependent reduction in both bulk carotid and cerebral vascular resistance. The mean maximal reduction was 39±5% at 20/s for the carotid bed and 37±6% at 20/s for the cerebral circulation. Stimulation of the superior sagittal sinus resulted in a frequency-dependent reduction in resistance that involved the cerebral circulation with little effect on bulk carotid resistance. The mean maximum reduction was 37±6% at 20/s for the cerebral circulation and 11±3% at 2/s for bulk carotid resistance. The more focused effects of superior sagittal sinus suggest a highly organised somatotopic arrangement of the trigeminal innervation of the cranial circulation. Such a physiological schema fits the known anatomy as reflected by the differential peptidergic innervation from the trigeminovascular system to cranial vessels and may be important in understanding the pathophysiology of migraine, cluster headache and subarachnoid haemorrhage. ©1997 Elsevier Science B.V. All rights reserved.     

Medical students as teachers and role models for their future colleagues

Medical schools seldom involve students in applicant recruitment. The authors describe the role of junior medical students in recruitment at the University of Ottawa, aiming to increase the Franco-Ontarian applicant pool for the French-language medical program. The students have designed workshops reflecting their study program and offered them, since 1997, to 719 Ontario French-language high school students and to 291 francophone undergraduate university students. The workshops emphasize role modeling by medical students who act as physician-teachers while attendees act as medical students. Evaluation measures include attendee surveys, medical student focus groups and faculty admissions statistics. Attendees give uniformly positive evaluations, highlighting the importance of role modeling. Medical students find teaching enjoyable and highly educational. Admissions statistics show that the Franco-Ontarian applicant pool has more than doubled in spite of an almost fourfold increase in tuition fees. This experience has shown that junior medical student involvement in recruitment activities can benefit both the trainees and their institution.     

Molecular epidemiology of chronic granulomatous disease in a series of 80 kindreds: identification of 31 novel mutations

Chronic granulomatous disease (CGD) results from constitutional inactivating mutations in the CYBB, NCF1, CYBA or NCF2 genes that encode subunits of phagocyte NADPH oxidase. We report the findings of molecular analysis of 80 kindred. In 75 unrelated male and 5 female probands, CGD was suspected on the basis of clinical symptoms, and biological samples were referred to our laboratory between 2000 and 2007. Seventy seven patients were found to have mutations in CYBB, NCF1, CYBA or NCF2 (52 different mutations including 31 mutations not previously reported). CYBB was the most frequently mutated gene (58 males and 3 females, 76%). In autosomal recessive forms of the disease, mutations were found in NCF1 (11 patients), NCF2 (3 patients) and CYBA (2 patients). We observed that significantly fewer females were affected by autosomal recessive CGD than expected (2 females/14 males; p=0.002), suggesting that female patients with CGD may be under diagnosed.     

The Impact of Socioeconomic Factors,Coverage and Access to Health on Heart Ischemic Disease Mortality in a Brazilian Southern State: A Geospatial Analysis

Background:No other disease has killed more than ischemic heart disease (IHD) for the past few years globally. Despite the advances in cardiology, the response time for starting treatment still leads patients to death because of the lack of healthcare coverage and access to referral centers.Objectives:To analyze the spatial disparities related to IHD mortality in the Parana state, Brazil.Methods:An ecological study using secondary data from Brazilian Health Informatics Department between 2013–2017 was performed to verify the IHD mortality. An spatial analysis was performed using the Global Moran and Local Indicators of Spatial Association (LISA) to verify the spatial dependency of IHD mortality. Lastly, multivariate spatial regression models were also developed using Ordinary Least Squares and Geographically Weighted Regression (GWR) to identify socioeconomic indicators (aging, income, and illiteracy rates), exam coverage (catheterization, angioplasty, and revascularization rates), and access to health (access index to cardiologists and chemical reperfusion centers) significantly correlated with IHD mortality. The chosen model was based on p < 0.05, highest adjusted R² and lowest Akaike Information Criterion.Results:A total of 22,920 individuals died from IHD between 2013–2017. The spatial analysis confirmed a positive spatial autocorrelation global between IDH mortality rates (Moran’s I: 0.633, p < 0.01). The LISA analysis identified six high-high pattern clusters composed by 66 municipalities (16.5%). GWR presented the best model (Adjusted R²: 0.72) showing that accessibility to cardiologists and chemical reperfusion centers, and revascularization and angioplasty rates differentially affect the IHD mortality rates geographically. Aging and illiteracy rate presented positive correlation with IHD mortality rate, while income ratio presented negative correlation (p < 0.05).Conclusion:Regions of vulnerability were unveiled by the spatial analysis where sociodemographic, exam coverage and accessibility to health variables impacted differently the IHD mortality rates in Paraná state, Brazil.Highlights

• The increase in ischemic heart disease mortality rates is related to geographical disparities.
• The IHD mortality is differentially associated to socioeconomic factors, exam coverage, and access to health.
• Higher accessibility to chemical reperfusion centers did not necessarily improve patient outcomes in some regions of the state.
• Clusters of high mortality rate are placed in regions with low amount of cardiologists, income and schooling.

     

Estimating the number of fractions by tumour site for European countries in 2012 and 2025: An ESTRO-HERO analysis

Background and purpose

The optimal number of radiotherapy fractions is a relevant input for planning resource needs. An estimation of the total number of fractions by country and tumour site is assessed for 2012 and 2025.