Fetal and neonatal IL-13 production during pregnancy and at birth and subsequent development of atopic symptoms

BACKGROUND: Cytokine production at the materno-fetal interface may influence the development of atopy-predisposing immune responses. Because IL-13 possesses IL-4-like activity and may regulate the immune responses observed in atopy, it may contribute to the expression of the atopic phenotype initiated during intrauterine life. OBJECTIVE: We sought to examine IL-13 expression by fetal and neonatal cells and the placenta. METHODS: The production of IL-13 by neonatal and fetal T cells was examined by culturing the cells in the presence or absence of PHA. Production of IL-13 at term was considered in the context of the later development of atopic disease in the child. IL-13 expression in the placenta was assessed by using immunohistochemistry. RESULTS: IL-13 immunoreactivity within the placenta was restricted to 16 to 27 weeks' gestation (6/6 positive vs 0/10 at >27 weeks' gestation). In contrast, spontaneous release of IL-13 by fetal mononuclear cells was first observed from 27 weeks' gestation but was undetectable after 37 weeks' gestation. PHA-stimulated mononuclear cells showed increased IL-13 levels in 80% of samples. Term babies (>37 weeks' gestation) with a parental history of atopy with atopic symptoms by 3 years of age produced significantly lower concentrations of PHA-induced IL-13 when compared with babies with no parental history of atopy (P =.034). CONCLUSION: Thus babies at risk of atopic disease in infancy display defective IL-13 production at birth. This may represent an inherent immaturity in the development of T cell-cytokine responses in babies at genetic risk for atopy or could be a consequence of downregulation of responses by other factors. Normal pregnancy, irrespective of atopic status, is associated with the production of appreciable quantities of IL-13 initially by the placenta and subsequently by the fetus. The regulation of this production and its consequences for the mother and fetus remains to be elaborated.     

The variable response of bacteria to free haemoglobin in the tissues

The local enhancement of infection by exogenous ferric iron, as ferric ammonium citrate, and by ferrous iron as guinea-pig haemoglobin, was assessed in studies with 55 strains of bacteria injected into the skin of guinea-pigs. The test organisms included Staphylococcus aureus, Streptococcus spp., Klebsiella spp., Escherichia coli and Pseudomonas aeruginosa. Four strains of Bacteroides spp. were tested with haemoglobin only. As previously reported with other strains, enhancement of infection by members of a given species by ferric iron was variable; in this study infection with only 11 of 59 strains was enhanced. Haemoglobin either of equal or lesser iron content was a more potent enhancer, affecting 27 of the 59 strains. The enhancement ranged from two-fold to 80-fold, the higher figures on the whole being characteristic of haemoglobin enhancement. Some few instances of depression by both haemoglobin and ferric ammonium citrate were noted. A few tests were made with systemic haemoglobin but the concentrations attainable were largely ineffective. Enhancement of infection did not appear to be related to the capacity of a strain to lyse or digest host red blood cells. In so far as guinea-pigs, whose antibacterial defences are lowered by ferric or ferrous iron, represent human subjects at risk of infection because of clinical circumstances characterised by excess of available iron--either exogenous or as a result of haemolysis--our results with organisms of a kind commonly associated with infection in hospitals suggest that only a small proportion of environmental bacteria can take advantage of any decreased resistance associated with iron excess.     

Single-column thalamocortical network model exhibiting gamma oscillations, sleep spindles, and epileptogenic bursts

To better understand population phenomena in thalamocortical neuronal ensembles, we have constructed a preliminary network model with 3,560 multicompartment neurons (containing soma, branching dendrites, and a portion of axon). Types of neurons included superficial pyramids (with regular spiking [RS] and fast rhythmic bursting [FRB] firing behaviors); RS spiny stellates; fast spiking (FS) interneurons, with basket-type and axoaxonic types of connectivity, and located in superficial and deep cortical layers; low threshold spiking (LTS) interneurons, which contacted principal cell dendrites; deep pyramids, which could have RS or intrinsic bursting (IB) firing behaviors, and endowed either with nontufted apical dendrites or with long tufted apical dendrites; thalamocortical relay (TCR) cells; and nucleus reticularis (nRT) cells. To the extent possible, both electrophysiology and synaptic connectivity were based on published data, although many arbitrary choices were necessary. In addition to synaptic connectivity (by AMPA/kainate, NMDA, and GABA(A) receptors), we also included electrical coupling between dendrites of interneurons, nRT cells, and TCR cells, and--in various combinations--electrical coupling between the proximal axons of certain cortical principal neurons. Our network model replicates several observed population phenomena, including 1) persistent gamma oscillations; 2) thalamocortical sleep spindles; 3) series of synchronized population bursts, resembling electrographic seizures; 4) isolated double population bursts with superimposed very fast oscillations (>100 Hz, "VFO"); 5) spike-wave, polyspike-wave, and fast runs (about 10 Hz). We show that epileptiform bursts, including double and multiple bursts, containing VFO occur in rat auditory cortex in vitro, in the presence of kainate, when both GABA(A) and GABA(B) receptors are blocked. Electrical coupling between axons appears necessary (as reported previously) for persistent gamma and additionally plays a role in the detailed shaping of epileptogenic events. The degree of recurrent synaptic excitation between spiny stellate cells, and their tendency to fire throughout multiple bursts, also appears critical in shaping epileptogenic events.     

Translocation (4;11) in acute myelogenous leukemia

A child with acute myelogenous leukemia is presented. Cytogenetic analysis of her leukemic cells revealed a (4;11)(q12;q23) translocation. The slight difference in the breakpoint on chromosome #4 from previously reported cases of t(4;11) may account for the degree of myeloid differentiation expressed. Acute leukemia associated with t(4;11) is a unique subgroup that originates in an early myeloid stem cell and carries a poor prognosis.     

Immune function did not decline with aging in apparently healthy, well-nourished women

Nutrition plays a crucial role in immune function. Most studies on age-associated changes in immunocompetence in healthy adults did not examine the nutritional status of participants extensively. Inadequate nutritional status may confound the relationship of aging and immune response. The purpose of this study was to examine age-related changes in parameters of acquired and innate immunity in healthy and generally well-nourished older (62-88 years) versus younger (20-40 years) women. Subjects were screened for participation using the health criteria of the SENIEUR protocol as well as a number of nutrition criteria related to undernutrition, and protein, iron, vitamin B12, and folate status. Young and old women did not differ in total T (CD3+), T-helper (CD4+), or T-cytotoxic (CD8+) cell number. However, older women tended to have lower T-cell proliferation response to concanavalin A (P < 0.10) and significantly reduced response to phytohemagglutinin (P < 0.05). No age-related changes were noted in natural killer cell number or cytotoxicity. Phagocytosis and subsequent oxidative burst activity also did not differ between young and old women. Most immune parameters were not compromised with aging in this cohort of apparently healthy, well-nourished women. These findings highlight the importance of simultaneous examination of health and nutritional status in studies of immune function with aging.     

Assessment of the effects of pixel loss on image quality in direct digital radiography

Modern digital radiographic 'flat panel' detectors can exhibit a progressive form of image degradation arising from non-functioning pixels. The effect of these 'dead pixels' on the quantitive image quality measures of modulation transfer function (MTF), noise power spectrum (NPS) and detective quantum efficiency (DQE) is investigated by a simulated degradation of images obtained from an Hologic EPEX system. The effects on the semi-quantitive measures obtained from contrast threshold test objects and resolution gratings are also investigated. Results suggest that the contrast-detail tests often employed in quality assurance measures are not sufficient to reveal the presence of dead pixels until well beyond the recommended replacement point for the flat panel detector. However, measurements of spatial resolution using a line pairs phantom were found to be more sensitive to pixel loss. Measurement of the MTF, NPS and DQE can reveal small changes in image quality with increasing pixel loss, with a distinctive pattern in the trend of the NPS.     

CD4 lymphocytes in the blood of HIV(+) individuals migrate rapidly to lymph nodes and bone marrow: support for homing theory of CD4 cell depletion

Recent studies have provided evidence that macrophages from Th1-prone mouse strains respond with an M1 profile, and macrophages from Th2-prone mouse strains respond with an M2 profile, characterized by the dominant production of NO or TGF-beta 1, respectively. We have shown that peritoneal macrophages from IL-12p40 gene knockout mice have a bias toward the M2 profile, spontaneously secreting large amounts of TGF-beta 1 and responding to rIFN-gamma with weak NO production. Moreover, IL-12p40KO macrophages are more permissive to Trypanosoma cruzi replication than their wild-type littermate cells. Prolonged incubation with rIL-12 fails to reverse the M2 polarization of IL-12p40KO macrophages. However, TGF-beta 1 is directly implicated in sustaining the M2 profile because its inhibition increases NO release from IL-12p40KO macrophages. IFN-gamma deficiency is apparently not the reason for TGF-beta 1 up-regulation, because rIFN-gamma KO macrophages produce normal amounts of this cytokine. These findings raise the possibility that IL-12 has a central role in driving macrophage polarization, regulating their intrinsic ability to respond against intracellular parasites.     

Changes in muscle responses to stimulation of the motor cortex induced by peripheral nerve stimulation in human subjects

The aim of this study was to determine whether prolonged, repetitive mixed nerve stimulation (duty cycle 1 s, 500 ms on-500 ms off, 10 Hz) of the ulnar nerve leads to a change in excitability of primary motor cortex in normal human subjects. Motor-evoked potentials (MEPs) generated in three intrinsic hand muscles [abductor digiti minimi (ADM), first dorsal interosseous (FDI) and abductor pollicis brevis (APB)] by focal transcranial magnetic stimulation were recorded during complete relaxation before and after a period of prolonged repetitive ulnar nerve stimulation at the wrist. Transcranial magnetic stimuli were applied at seven scalp sites separated by 1 cm: the optimal scalp site for eliciting MEPs in the target muscle (FDI), three sites medial to the optimal site and three sites lateral to the optimal stimulation site. The area of the MEPs evoked in the ulnar-(FDI, ADM) but not the median-innervated (APB) muscles was increased after prolonged ulnar nerve stimulation. Centre of gravity measures demonstrated that there was no significant difference in the distribution of cortical excitability after the peripheral stimulation. F-wave responses in the intrinsic hand muscles were not altered after prolonged ulnar nerve stimulation, suggesting that the changes in MEP areas were not the result of stimulus-induced increases in the excitability of spinal motoneurones. Control experiments employing transcranial electric stimulation provided no evidence for a spinal origin for the excitability changes. These results demonstrate that in normal human subjects the excitability of the cortical projection to hand muscles can be altered in a manner determined by the peripheral stimulus applied.