Atopy, lung function, and obstructive airways disease after prenatal exposure to famine

BACKGROUND: Associations have been found between a large head size at birth and atopy, and between low birth weight and obstructive airways disease. A study was undertaken of people born around the time of the Dutch famine in 1944-5 to determine the effects of maternal malnutrition during specific periods of gestation on the prevalence of obstructive airways disease and atopy. METHODS: Nine hundred and twelve people aged about 50, born at term between November 1943 and February 1947 in Amsterdam, were asked about their medical history. Lung function was measured in 733 and serum concentrations of total IgE and specific IgE against mite, pollen and cat were measured in 726. Those exposed in late, mid, and early gestation (exposed participants) were compared with those born before or conceived after the famine (non-exposed participants). RESULTS: Exposure to famine during gestation affected neither the concentrations of total or specific IgE nor lung function values. The prevalence of obstructive airways disease was increased in people exposed to famine in mid gestation (odds ratio adjusted for sex 1.7, 95% confidence interval (CI) 1.1 to 2.6) and tended to be higher in those exposed in early gestation (odds ratio 1.5, 95% CI 0. 9 to 2.6). CONCLUSIONS: The observed increase in the prevalence of obstructive airways disease in people exposed to famine in mid and early gestation was not parallelled by effects on IgE concentrations or lung function. The link between exposure to famine in mid and early gestation and obstructive airways disease in adulthood suggests that fetal lungs can be permanently affected by nutritional challenges during periods of rapid growth.     

Fc-Fc interactions of human IgG4 require dissociation of heavy chains and are formed predominantly by the intra-chain hinge isomer

Human IgG4 antibodies are remarkable not only because they can dynamically exchange half-molecules (Fab-arm exchange) but also for their ability to interact with the Fc part of IgG4 and other IgG subclasses. This rheumatoid factor-like binding of IgG4 does not appear to take place spontaneously, because it is only observed to solid-phase or antigen-bound IgG. We hypothesized that Fc-Fc interactions might involve (partial) dissociation of heavy chains. We investigated the molecular basis of these Fc-Fc interactions, and found that the structural features important for the exchange reaction also control the Fc binding activity. In particular, if arginine-409 in the CH(3)-CH(3) interface in IgG4 is mutated to lysine (the equivalent in IgG1), Fc-Fc interactions are formed 3 orders of magnitude less efficiently compared to the wild-type. This mutation was previously found to increase the CH(3)-CH(3) interaction strength in IgG4. Furthermore, of the two hinge isomers of IgG4, the intra-chain (non-covalently linked) form was found to form Fc-Fc interactions, but not the inter-chain form. Together, these results demonstrate that Fc-Fc interactions of IgG4 involve (partial or complete) dissociation of heavy chains. The promiscuity to other IgG subclasses suggests that IgG4 might act as scavenger to IgG molecules with impaired structural integrity.     

Cognitive defense style and WISC-R P > V sign in juvenile recidivists

Investigated the relationship of WISC-R, P > V sign and cognitive defense style to juvenile recidivism. Sixty-eight male juvenile recidivists and 68 nonrecidivists were administered the WISC-R and Byrne's R-S scale as part of a standard diagnostic battery. Although recidivists were found to have significantly higher P > V differences than non-recidivists, presence of P > V sign did not distinguish recidivists from non-recidivists. While recidivists were found to be significantly more sensitizing than non-recidivists, R-S scores were not found to be related to magnitude of P > V sign. Two separate classes of behaviors were suggested as increasing the probability of recidivism.     

Abnormal development of the vasculosyncytial membrane in early pregnancy failure

OBJECTIVE: To investigate chorionic villous vasculogenesis (maturation) and development of the vasculosyncytial membrane (margination) using CD34 immunohistochemistry. DESIGN: Case-control study. SETTING: Microscopic analysis of first trimester chorionic villi. PATIENT(S): Twelve patients with anembryonic pregnancies, 12 with embryonic death, and 12 with terminated normal pregnancies. INTERVENTION(S): Quantitative analysis of chorionic villi blinded to group and gestational age using CD34 immunohistochemistry. MAIN OUTCOME MEASURE(S): Vascular parameters (mean functional vascular area, vessels with a lumen, and hemangiogenetic cords, peripherally or centrally located). RESULT(S): Terminated normal pregnancies show significantly more vessels per chorionic villus (maturation) (mean +/- SEM) in comparison with embryonic deaths and anembryonic pregnancies (5.3 +/- 0.3 vs. 1.4 +/- 0.2 and 0.7 +/- 0.1), located mainly peripherally (margination) (3.0 +/- 0.2 vs. 0.9 +/- 0.2 and 0.2 +/- 0.0). Anembryonic pregnancies show significantly more centrally located cords in comparison with embryonic deaths and termination of pregnancies (3.3 +/- 0.2 vs. 2.7 +/- 0.2 and 1.5 +/- 0.1). CONCLUSION(S): A defective chorionic villous vascularization, demonstrating inadequate vasculogenesis and abnormal development of the vasculosyncytial membrane, is seen in pregnancies complicated by embryonic death and is even more pronounced in anembryonic pregnancies. Initiation of placental vasculogenesis is a basic feature in all types of pregnancy and is subsequently modulated directly or indirectly by embryonic signaling.     

Maternal admission characteristics as risk factors for preterm birth

OBJECTIVE: The aim of this study is to identify a subset of women presenting with preterm labor not responding upon tocolytic therapy, eventually resulting in preterm birth. STUDY DESIGN: The maternal admission characteristics of 185 women with preterm labor receiving tocolysis were analysed for risk factors that could predict which women will deliver within 48 h after the start of tocolysis, or before 34 weeks gestation. Univariate analysis and multivariate logistic regression analysis was performed. RESULTS: Logistic regression analysis identified the following risk factors for delivery within 48 h after the start of tocolysis: cervical dilatation at admission (odds ratio (OR, cm(-1)) 1.47; 95% confidence interval (CI), 1.44-1.49), elevated leukocyte count at admission (per 10(3) leukocytes/mm(3)) (OR 1.27; 95% CI, 1.26-1.28), use of nifedipine (OR 0.49; 95% CI, 0.26-0.49), and developing signs suggestive of chorioamnionitis following admission (OR 2.12; 95% CI, 1.04-4.33). For delivery before 34 weeks of gestation the following risk factors were identified: use of steroids (OR 5.87; 95% CI, 2.34-14.7), use of nifedipine (OR 0.46; 95% CI, 0.27-0.85), developing signs suggestive of chorioamnionitis following admission (OR 10.6; 95% CI, 3.1-35.9), and preterm premature rupture of the membranes (OR 12; 95% CI, 4.1-35.2). CONCLUSIONS: Risk factors associated for delivery within 48 h after starting tocolysis are: cervical dilatation at admission, elevated leukocyte count at admission, and developing signs suggestive of chorioamnionitis following admission. Use of nifedipine was associated with a delay of delivery >48 h. Risk factors associated for delivery within 34 weeks gestation are: use of steroids, developing signs suggestive of chorioamnionitis following admission, and ruptured membranes. Use of nifedipine was associated with a delay >34 weeks.