Studies of cellular immunity in children with measles

Being a dissertation presented in fulfilment of the requirements governing the degree of Master of Science in the School of Medicine, University of the Witwatersrand. JOHANNESBURG September 1978There have l=eg been two clinical Indications of the significance of cell-mediated Immunity to measles, namely, the cutaneous delayed hypersensitivity reaction to tuberculin Is greatly depressed or even absent during Infection and that Individuals with hypogammaglobullneraia recover normally from measles. The experiu- ntal work presented In this dissertation basically involved the study of the cellular immune status of children acutely infected with measles virus. Lymphocyte blastogenlsis and lymphoklne production, two techniques that have been previously employed In Investigations of clinical conditions known to he associated with cellular immune defects, were adapted for use in the present study. Lymphocyte transformation studies of measles MN cells revealed the existence of elevated unstloul.ted or •spontaneous' incorporation of thymidine after overnight incubation, later decreasing to lower levels. The significance of the latter is speculative but most probably reflects in vivo activation of MN cell, by measles antigen. PI1A activation of measles MN cells was essentially normal over a range of different mitogen concentrations and no inhibition Of normal lymphocyte transformation was apparent using measles MN cell supernatants or acute serum. In contrast, allogeneic stimulation of measles MN cells in the two-way Mi*, resulted in *1 vt wiw \ xf 4 A m e a a l e s MN -1 L f _ * V . < , 1 { cells respond poorly to allogeneic activation, but when mi cornycin C-treated, they also failed to adequately stimulate control responding cells. Although no ready explanation for this puzzling finding is apparent the possibility exists that different lymphocyte subpopulations are adversely affected by measles virus infection. To assess lymphok^ne production a two-stage migration assay was i U 11zed. The first stage consisted of pulsing MN cells with PHA to induce lymphokine production and the second stage involved the incubation of indicator cells with and without lymphokinecontaining supernatants. Using on agarose migration system, it was snovn that measles MN cells failed to produce LIF while the capillary tube migration system using guinea-pig PEC, demonstrated • lack - f MIF activity too. In contrast to the results obtained by measuring thymidine incorporation after 18 hours of incubation, measles MN cells aid not produce LIF 'spontaneously1. In addition, supernatants from unstimulated measles MN cells did not inhibit the production of LIF by normal PHA-pulsed MN cells. These results suggest that a specific lymphokine-producing cell population may be adversely affected by measles infection. An attempt at correcting this defect by treatment of measles MN c.11s in Vitro with levamisole was however, unsuccessful at the concentration used in this study. Virological examination of measles MN cell culture supernatants demonstrated the presence of papovavirus particles in a small number of patients. Specific immunofluorescent staining for the virus in MN cell preparations was however unsuccessful. These results suggest either reactivation of a latent virus infection during the course of measles or simply, contamination of specimens during processing in a ’irological laboratory. The effect of measles on monocyte function was assessed in vitro using a modified Boyden amber technique. The monocytes of measles patients were shown to migrate adequately to tbr chemoattractant casein. Although the migration of measles PMN cells in vivo was found to be depressed as assessed by the Rebuck skin-window technique, measles monocytes were found to migrate in sufficient numbers after 24 hours. These results imply that the adverse effect? of measles infection on cellular immunity is probably confined to lymphocytes

Prefrontal Interneurons: Populations, Pathways, and Plasticity Supporting Typical and Disordered Cognition in Rodent Models

Prefrontal cortex (PFC) inhibitory microcircuits regulate the gain and timing of pyramidal neuron firing, coordinate neural ensemble interactions, and gate local and long-range neural communication to support adaptive cognition and contextually tuned behavior. Accordingly, perturbations of PFC inhibitory microcircuits are thought to underlie dysregulated cognition and behavior in numerous psychiatric diseases and relevant animal models. This review, based on a Mini-Symposium presented at the 2022 Society for Neuroscience Meeting, highlights recent studies providing novel insights into: (1) discrete medial PFC (mPFC) interneuron populations in the mouse brain; (2) mPFC interneuron connections with, and regulation of, long-range mPFC afferents; and (3) circuit-specific plasticity of mPFC interneurons. The contributions of such populations, pathways, and plasticity to rodent cognition are discussed in the context of stress, reward, motivational conflict, and genetic mutations relevant to psychiatric disease

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on Dietary Reference Values for energy

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) derived dietary reference values for energy, which are provided as average requirements (ARs) of specified age and sex groups. For children and adults, total energy expenditure (TEE) was determined factorially from estimates of resting energy expenditure (REE) plus the energy needed for various levels of physical activity (PAL) associated with sustainable lifestyles in healthy individuals. To account for uncertainties inherent in the prediction of energy expenditure, ranges of the AR for energy were calculated with several equations for predicting REE in children (1-17 years) and adults. For practical reasons, only the REE estimated by the equations of Henry (2005) was used in the setting of the AR and multiplied with PAL values of 1.4, 1.6, 1.8 and 2.0, which approximately reflect low active (sedentary), moderately active, active and very active lifestyles. For estimating REE in adults, body heights measured in representative national surveys in 13 EU Member States and body masses calculated from heights assuming a body mass index of 22 kg/m2 were used. For children, median body masses and heights from the WHO Growth Standards or from harmonised growth curves of children in the EU were used. Energy expenditure for growth was accounted for by a 1 % increase of PAL values for each age group. For infants (7-11 months), the AR was derived from TEE estimated by regression equation based on doubly labelled water (DLW) data, plus the energy needs for growth. For pregnant and lactating women, the additional energy for the deposition of newly formed tissue, and for milk output, was derived from data obtained by the DLW method and from factorial estimates, respectively. The proposed ARs for energy may need to be adapted depending on specific objectives and target populations

How to design an art-science program? Self-reported benefits for artists and scientists in the VI4 artist-in-residence program.

While many new programs bridge the arts and sciences, a data-based examination of art-science program design can lead to more efficient programming. The Vanderbilt Institute for Infection, Immunology, and Inflammation Artist-in-Residence program is a virtual program that brings together undergraduate student "artists" and faculty-level "scientists" to generate science-art content. We have recruited over 80 artists and 50 scientists to collaborate in creating visual science communication content. Using self-reported data from both groups, we performed qualitative and quantitative analyses to define sources for negative and positive experiences for artists and scientists. We also identify areas for improvement and key features for in producing a positive experience. We found that artists participants had more positive responses about "learning something new" from the program than scientists. We also found that for both artists and scientists the length of the program and the virtual nature were identified as key features that could be improved. However, the most surprising aspect of our analysis suggests that for both "way of thinking" and "science communication to the public or general audience," were seen as significant beneficial gains for scientists compared to artists. We conclude this analysis with suggestions to enhance the benefits and outcomes of an art-science program and ways to minimize the difficulties, such as communication and collaboration, faced by participants and program designers

Discovery of CYT997: a structurally novel orally active microtubule targeting agent

CYT997 was discovered as a potent tubulin polymerization inhibitor possessing potent cytotoxic activity against a range of cancer cells. Details of SAR studies, pharmacokinetic investigations and synthesis of compounds leading to the discovery of CYT997 are reported

Functional partnership between mGlu3 and mGlu5 metabotropic glutamate receptors in the central nervous system

mGlu5 receptors are involved in mechanisms of activity-dependent synaptic plasticity, and are targeted by drugs developed for the treatment of CNS disorders. We report that mGlu3 receptors, which are traditionally linked to the control of neurotransmitter release, support mGlu5 receptor signaling in neurons and largely contribute to the robust mGlu5 receptor-mediated polyphosphoinositide hydrolysis in the early postnatal life. In cortical pyramidal neurons, mGlu3 receptor activation potentiated mGlu5 receptor-mediated somatic Ca2+ mobilization, and mGlu3 receptor-mediated long-term depression in the prefrontal cortex required the endogenous activation of mGlu5 receptors. The interaction between mGlu3 and mGlu5 receptors was also relevant to mechanisms of neuronal toxicity, with mGlu3 receptors shaping the influence of mGlu5 receptors on excitotoxic neuronal death. These findings shed new light into the complex role played by mGlu receptors in physiology and pathology, and suggest reconsideration of some of the current dogmas in the mGlu receptor field