Lack of association between IgA deficiency and respiratory atopy in young male adults.

BACKGROUND: The issue of atopy and increased serum IgE in IgA deficiency is still a matter of debate. The aim of this study was to evaluate the prevalence of IgA deficiency and its relationship with respiratory atopy. MATERIALS AND METHODS: A retrospective study on 4700 consecutive young males (age range 18-23), who underwent a health screen for admission to the Italian Airforce Academy between 1993 and 1995 was conducted. Serum IgA was measured by immunoturbidimetry and total and specific IgE by fluorescent enzyme immunoassay (Phadiatop FEIA, Pharmacia Cap System). Airway responsiveness was assessed by methacholine challenge. RESULTS: IgA deficiency was detected in 0.34% (16/4700) subjects and atopy was detected in 8.6% (406/4700). The mean IgA was 243 mg/dl (95% CI 107, 442) in the 406 atopic subjects and 238 mg/dl (95% CI 100, 441) in 1544 controls. Only 6 (37.5%) of the IgA deficient subjects had subnormal IgE levels and 6 were positive in the fluorescent EIA. None of the IgA deficient patients presented with respiratory hyper-reactivity. CONCLUSION: Atopy is not more prevalent in young male adult IgA deficient subjects, who rather display a high frequency of recurrent sinusitis.

Contribution of endogenously expressed Trp1 to a Ca2+-selective, store-operated Ca2+ entry pathway.

Heterologous expression of the transient receptor potential-1 gene product (Trp1) encodes for a Ca2+ entry pathway, though it is unclear whether endogenous Trp1 contributes to a selective store-operated Ca2+ entry current. We examined the role of Trp1 in regulating both store-operated Ca2+ entry and a store-operated Ca2+ entry current, I(SOC), in A549 and endothelial cells. Twenty different 'chimeric' 2'-O-(2-methoxy)ethylphosphothioate antisense oligonucleotides were transfected separately using cationic lipids and screened for their ability to inhibit Trp1 mRNA. Two hypersensitive regions were identified, one at the 5' end of the coding region and the second in the 3' untranslated region beginning six nucleotides downstream of the stop codon. Antisense oligonucleotides stably decreased Trp1 at concentrations ranging from 10 to 300 nM, for up to 72 h. Thapsigargin increased global cytosolic Ca2+ and activated a I(SOC), which was small (-35 pA @ -80 mV), reversed near +40 mV, inhibited by 50 microM La3+, and exhibited anomalous mole fraction dependence. Inhibition of Trp1 reduced the global cytosolic Ca(2+) response to thapsigargin by 25% and similarly reduced I(SOC) by 50%. These data collectively support a role for endogenously expressed Trp1 in regulating a Ca2+-selective current activated upon Ca2+ store depletion.

Sibship size, birth order, and atopy in 11,371 Italian young men.

BACKGROUND: Having a low number of siblings and a low birth order has been reported to be a relevant risk factor for development of atopic diseases and skin sensitization to common inhalants. Although the inverse association of atopy with sibship size has been confirmed repeatedly, the association with birth order has provided conflicting results. This possibly is due to the relatively small size of the population sample examined. OBJECTIVE: The objective of this study was to investigate the relation between sibship size, birth order, and atopy in a very large population sample, highly homogeneous for age and sex. METHODS: This was a retrospective survey of 11,371 Italian young men, 18 to 24 years old, all candidates for enrollment in the Italian Air Force. Demographic data had been collected by a standard questionnaire. Specific IgE for locally relevant airborne allergens had been tested by a multi-RAST assay (CAP-Phadiatop). RESULTS: The prevalence of atopy (defined as a high level of specific IgE against inhalants [cut-point >1.2 log RU]) was inversely related to the total number of siblings (25% in those with no siblings and 9% in those with five or more siblings), with a mean of a 3% decrease in prevalence for each added sibling. This relation persisted after adjustment for relevant variables such as father's education and rural and southern residence. An independent association between birth order and atopy was also observed because the decrease in atopy prevalence with increasing numbers of older siblings was significantly steeper than that found with the number of younger siblings (chi2 = 179, df = 1, p < 0.0001). CONCLUSIONS: In a very large and homogeneous population sample of a Mediterranean country, not only sibship size but also birth order was significantly associated with atopy. This observation further highlights the role of family structure in the development of atopy and supports the hypothesis that cross-infections acquired early in infancy or in later childhood might prevent development of atopy later in life.

[Interferon treatment of HCV-correlated active chronic hepatitis and hepatic cirrhosis: personal experience]. / La nostra esperienza nel trattamento con interferone dell'epatite cronica attiva e della cirrosi epatica HCV correlate.

BACKGROUND AND AIMS: IFN therapy is the only method of treating HCV-correlated active chronic hepatitis given that Ribavirin is still undergoing clinical trials. METHODS: A total of 166 patients received treatment: 73 (aged <50 years) with active chronic hepatitis and 45 (aged <50) with CHILD hepatic cirrhosis; 24 patients were used as a control group. The first group was treated with alpha-IFN and the second with beta-IFN. RESULTS: The complete response was evaluated at 12 months and the sustained response at 18 months using chi2 according to Yates. Highly significant results (p<0.001) were obtained in the two groups compared to controls, but no statistically significant differences were observed between the various alpha-IFN subgroups. Treatment with alpha-IFN and beta-IFN was effective in reducing indices of cytolysis and viral activities. CONCLUSIONS: IFN treatment positively alters the hepatic histological evolution: the authors affirm that even in advanced cases of chronic liver disease, treatment with IFN may slow down the natural evolution of the disease.

A mouse model for the learning and memory deficits associated with neurofibromatosis type I.

Neurofibromatosis type I (NF1) is one of the most commonly inherited neurological disorders in humans, affecting approximately one in 4,000 individuals. NF1 results in a complex cluster of developmental and tumour syndromes that include benign neurofibromas, hyperpigmentation of melanocytes and hamartomas of the iris. Some NF1 patients may also show neurologic lesions, such as optic pathway gliomas, dural ectasia and aqueduct stenosis. Importantly, learning disabilities occur in 30% to 45% of patients with NF1, even in the absence of any apparent neural pathology. The learning disabilities may include a depression in mean IQ scores, visuoperceptual problems and impairments in spatial cognitive abilities. Spatial learning has been assessed with a variety of cognitive tasks and the most consistent spatial learning deficits have been observed with the Judgement of Line Orientation test. It is important to note that some of these deficits could be secondary to developmental abnormalities and other neurological problems, such as poor motor coordination and attentional deficits. Previous studies have suggested a role for neurofibromin in brain function. First, the expression of the Nf1 gene is largely restricted to neuronal tissues in the adult. Second, this GTPase activating protein may act as a negative regulator of neurotrophin-mediated signalling. Third, immunohistochemical studies suggest that activation of astrocytes may be common in the brain of NF1 patients. Here, we show that the Nf1+/- mutation also affects learning and memory in mice. As in humans, the learning and memory deficits of the Nf1+/- mice are restricted to specific types of learning, they are not fully penetrant, they can be compensated for with extended training, and they do not involve deficits in simple associative learning.

Impaired learning in mice with abnormal short-lived plasticity.

BACKGROUND: Many studies suggest that long term potentiation (LTP) has a role in learning and memory. In contrast, little is known about the function of short-lived plasticity (SLP). Modeling results suggested that SLP could be responsible for temporary memory storage, as in working memory, or that it may be involved in processing information regarding the timing of events. These models predict that abnormalities in SLP should lead to learning deficits. We tested this prediction in four lines of mutant mice with abnormal SLP, but apparently normal LTP-mice heterozygous for a alpha-calcium calmodulin kinase II mutation (alpha CaMKII +/-) have lower paired-pulse facilitation (PPF) and increased post-tetanic potentiation (PTP); mice lacking synapsin II (SyII-/-), and mice defective in both synapsin I and synapsin II (SyI/II-/-), show normal PPF but lower PTP; in contrast, mice just lacking synapsin I (SyI-/-) have increased PPF, but normal PTP. RESULTS: Our behavioral results demonstrate that alpha CaMKII +/-, SyII-/- and SyI/II-/- mutant mice, which have decreased PPF or PTP, have profound impairments in learning tasks. In contrast, behavioral analysis did not reveal learning deficits in SyI-/- mice, which have increased PPF. CONCLUSIONS: Our results are consistent with models that propose a role for SLP in learning, as mice with decreased PPF or PTP, in the absence of known LTP deficits, also show profound learning impairments. Importantly, analysis of the SyI-/- mutants demonstrated that an increase in PPF does not disrupt learning.

Deficient plasticity in the primary visual cortex of alpha-calcium/calmodulin-dependent protein kinase II mutant mice.

The recent characterization of plasticity in the mouse visual cortex permits the use of mutant mice to investigate the cellular mechanisms underlying activity-dependent development. As calcium-dependent signaling pathways have been implicated in neuronal plasticity, we examined visual cortical plasticity in mice lacking the alpha-isoform of calcium/calmodulin-dependent protein kinase II (alpha CaMKII). In wild-type mice, brief occlusion of vision in one eye during a critical period reduces responses in the visual cortex. In half of the alpha CaMKII-deficient mice, visual cortical responses developed normally, but visual cortical plasticity was greatly diminished. After intensive training, spatial learning in the Morris water maze was severely impaired in a similar fraction of mutant animals. These data indicate that loss of alpha CaMKII results in a severe but variable defect in neuronal plasticity.

Asthma and bronchial reactivity: a contribution from multivariate analysis.

This study was performed on 508 young male candidates on the military pilot course of the Air Force Academy. Observations of the following parameters were made: immunoglobulin E (IgE) level, skin sensitivity test (prick test) to most common continuous and seasonal allergens, and results of nonspecific bronchial provocation tests with methacholine. The analysis strategy that has been developed consists of two techniques, "multiple correspondence analysis (MCA)" and "automatic classification". The correlation between the categories of the characters evaluated are: degree of high skin reactivity in relation to high IgE levels, hyperreactivity to low methacholine dose (noticed mainly in subjects allergic to continuous antigens), low degree of skin reactivity (both to continuous and seasonal antigens and found in relation to a low methacholine dose) and medium and low IgE levels. The cluster analysis defined three different classes of subjects: 1) 51.97% of the total observed subjects. 68.82% of those subjects that showed IgE levels above 7300 and a high reactivity to low methacholine dose; 2) 15.94% of subjects with a severe allergy to pollens; and 3) 32.09% of subjects with IgE levels lower than 900, low bronchial reactivity and no allergic component for either seasonal or continuous antigens. The use of multivariate statistical techniques in this field of pathophysiology has allowed a confirmative-explorative study of allergic phenomena in relation to several characters, and the determination of classes of subjects characterized by well-defined categories.

Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein.

The cAMP-responsive element-binding protein (CREB) has been implicated in the activation of protein synthesis required for long-term facilitation, a cellular model of memory in Aplysia. Our studies with fear conditioning and with the water maze show that mice with a targeted disruption of the alpha and delta isoforms of CREB are profoundly deficient in long-term memory. In contrast, short-term memory, lasting between 30 and 60 min, is normal. Consistent with models claiming a role for long-term potentiation (LTP) in memory, LTP in hippocampal slices from CREB mutants decayed to baseline 90 min after tetanic stimulation. However, paired-pulse facilitation and posttetanic potentiation are normal. These results implicate CREB-dependent transcription in mammalian long-term memory.

When good news is bad news: medical wellness as a nonevent in undergraduates.

Study 1 demonstrated that information about healthy functioning can amplify health concerns and erode diagnostic confidence. Undergraduate Ss received a hypothetical test showing some level of cells associated either with pathology or with its absence. The moderate wellness result produced low confidence in one's health estimate and was distressing to receive. Wellness information may represent an ambiguous nonevent when testing for disease. Study 2 tested this thesis by adding Ss who adopted a recovering role to those adopting an illness role. Judgmental uncertainty was greatest--and equivalent--among recovering Ss given the moderate illness result and among ailing Ss given a moderate wellness result, and both groups were most willing to consider taking a risky treatment for the disease.

Delayed costs of suppressed pain.

The study demonstrates that the rebound effect of thought suppression (Wegner, 1989) has an analog in the experience of somatic discomfort. During a cold-pressor pain induction, 63 Ss were instructed either to concentrate on their room at home (distraction), to pay close attention to their hand sensations (monitoring), or to remove awareness of those sensations from mind (suppression). Two min of postpressor pain ratings showed that monitoring produced the most rapid recovery from the pain and that suppression produced the slowest. Suppression also contaminated the interpretation of a subsequent somatic stimulation; later in the experimental hour, Ss who had suppressed their cold-pressor discomfort rated an innocuous vibration as more unpleasant than did other Ss. The strategies are discussed for their necessarily distinct processes of goal evaluation and their possibly differential drain on perceived coping capacities.

Asymmetry of doubt in medical self-diagnosis: the ambiguity of "uncertain wellness".

In 2 studies Ss received a clear or an unclear diagnosis, indicating either disease or no disease. In Experiment 1, Ss responded to a hypothetical bacteria test. In Experiment 2, Ss performed 2 saliva tests purportedly measuring risk for pancreatic disorders. Responses to the unclear well diagnosis were unique in several ways. Ss thought the test more invalid, inferred a greater likelihood of illness from a 2nd identical result, saw the disorder as more pernicious, and held no self-protective beliefs about the test or the disease. Moreover, desire for treatment among these Ss was as great as among those receiving a clear diagnosis of illness. Possible mechanisms are discussed, as are potential applications to clinical issues and to the development and maintenance of hypochondriacal health concerns.

Beyond attentional strategies: cognitive-perceptual model of somatic interpretation.

The meaning people assign to physical sensations can have profound implications for their physical and psychological health. A predominant research question in somatic interpretation asks if it is more adaptive to distract one's attention away from a potentially unpleasant sensation or to focus one's attention on it. This question, however, has yielded equivocal answers. Many apparent ambiguities in this research can be traced to a failure to distinguish the content of a person's attention from its mere direction or degree. A model of somatic interpretation is discussed, incorporating not only perceptual focus but also the attributions, goals, coping strategies, and prior hypotheses of the perceiver, thus delineating the psychobiological conditions under which various attentional strategies should be adaptive. In contrast to the prevailing concern with when and why somatic distraction doesn't "work," this conceptual analysis also considers when and why somatic attention does. Theoretical and methodological issues are discussed, as is the potential utility of somatic attention in cardiac rehabilitation and multiple sclerosis.

Perceived self-efficacy in coping with cognitive stressors and opioid activation.

This experiment tested the hypothesis that perceived self-inefficacy in exercising control over cognitive stressors activates endogenous opioid systems. Subjects performed mathematical operations under conditions in which they could exercise full control over the cognitive task demands or in which the cognitive demands strained or exceeded their cognitive capabilities. Subjects with induced high perceived self-efficacy exhibited little stress, whereas those with induced low perceived self-efficacy experienced a high level of stress and autonomic arousal. Subjects were then administered either an inert saline solution or naloxone, an opiate antagonist that blocks the analgesic effects of endogenous opiates, whereupon their level of pain tolerance was measured. The self-efficacious nonstressed subjects gave no evidence of opioid activation. The self-inefficacious stressed subjects were able to withstand increasing amounts of pain stimulation under saline conditions. However, when endogenous opioid mechanisms that control pain were blocked by naloxone, the subjects were unable to bear much pain stimulation. This pattern of changes suggests that the stress-induced analgesia found under the saline condition was mediated by endogenous opioid mechanisms and counteracted by the opiate antagonist.