Serum-mediated inhibition of human lymphocyte fc gamma-receptors in extrinsic and intrinsic bronchial asthma

Sera from 48 patients with extrinsic asthma and 37 with intrinsic asthma were screened for immune complexes using the EA-rosette inhibition assay. Significant levels of EA-rosette inhibition were found in both groups when compared with normal sera. The serum inhibitory factor(s) is, however, more likely to be an anti-lymphocyte antibody of the IgM class than an immune complex as originally expected.     

Intrinsic and extrinsic motivation for smoking cessation

An intrinsic-extrinsic model of motivation for smoking cessation was evaluated with 2 samples (ns = 1.217 and 151) of smokers who requested self-help materials for smoking cessation. Exploratory and confirmatory principal components analysis on a 36-item Reasons for Quitting (RFQ) scale supported the intrinsic-extrinsic motivation distinction. A 4-factor model, with 2 intrinsic dimensions (concerns about health and desire for self-control) and 2 extrinsic dimensions (immediate reinforcement and social influence), was defined by 20 of the 36 RFQ items. The 20-item measure demonstrated moderate to high levels of internal consistency and convergent and discriminant validity. Logistic regression analyses indicated that smokers with higher levels of intrinsic relative to extrinsic motivation were more likely to achieve abstinence from smoking.     

Intrinsic and extrinsic modulation of a single central pattern generating circuit

Intrinsic and extrinsic neuromodulation are both thought to be responsible for the flexibility of the neural circuits (central pattern generators) that control rhythmic behaviors. Because the two forms of modulation have been studied in different circuits, it has been difficult to compare them directly. We find that the central pattern generator for biting in Aplysia is modulated both extrinsically and intrinsically. Both forms of modulation increase the frequency of motor programs and shorten the duration of the protraction phase. Extrinsic modulation is mediated by the serotonergic metacerebral cell (MCC) neurons and is mimicked by application of serotonin. Intrinsic modulation is mediated by the cerebral peptide-2 (CP-2) containing CBI-2 interneurons and is mimicked by application of CP-2. Since the effects of CBI-2 and CP-2 occlude each other, the modulatory actions of CBI-2 may be mediated by CP-2 release. Although the effects of intrinsic and extrinsic modulation are similar, the neurons that mediate them are active predominantly at different times, suggesting a specialized role for each system. Metacerebral cell (MCC) activity predominates in the preparatory (appetitive) phase and thus precedes the activation of CBI-2 and biting motor programs. Once the CBI-2s are activated and the biting motor program is initiated, MCC activity declines precipitously. Hence extrinsic modulation prefacilitates biting, whereas intrinsic modulation occurs during biting. Since biting inhibits appetitive behavior, intrinsic modulation cannot be used to prefacilitate biting in the appetitive phase. Thus the sequential use of extrinsic and intrinsic modulation may provide a means for premodulation of biting without the concomitant disruption of appetitive behaviors.     

Cromolyn in extrinsic and intrinsic asthma

Cromolyn sodium was evaluated in 30 patients with intrinsic bronchial asthma and in 29 patients with extrinsic bronchial asthma using a double-blind crossover method. Each patient was studied during a base line, placebo, and cromolyn period. Daily evaluation was performed with regard to upper respiratory tract symptoms, lower respiratory tract symptoms, oral medication scores, use of sympathomimetic agents by aerosolization and peak expiratory flow rates measured 5 times a day. Weekly evaluation consisted of a physician's evaluation and a timed vital capacity. At the end of each test period spirometry, airway resistance and an exercise tolerance test were performed. Evaluation of the intrinsic asthmatic patients revealed significant improvement during the cromolyn period as compared to the placebo and base line periods with regard to the daily recorded variables and the physician's evaluation. Study of the other parameters showed no significant trend. Evaluation of the use of cromolyn in extrinsic bronchial asthma revealed no general trends for any of the parameters measured.     

Intrinsic and extrinsic factors of turning preferences in humans

Turning behaviour in 107 adolescents was observed during walking and running under different temporal and biomechanical constraints. Participants ran and walked back and forth between two lines 9.5m apart in a neutral environment. All of the turns that the participants made to change direction between the lines were videotaped. A general preference for turning leftwards was observed with the percentage being higher in the unconstrained running condition when compared to the walking condition (71% versus 59%, respectively). This intrinsic preference was easily overruled when positional constraints on the starting position were imposed. Such positional constraints did not, however, suppress the intrinsic directional bias observed during running. It is concluded that turning preference in humans is the result of a complex interaction between intrinsic preferences and externally imposed task constraints.     

Blood lymphocyte subpopulations in extrinsic and intrinsic asthmatics

Blood leukocyte numbers and proportions of T lymphocyte subsets were studied in extrinsic asthmatics (EA), intrinsic asthmatics (IA), IA systemically treated with corticosteroids (IA + C), and in age-matched control subjects. The EA and IA showed an increased number of eosinophils. During corticosteroid therapy of IA, the eosinophil number remained elevated, whereas there was a slight decrease in the number of circulating lymphocytes. The proportion of T cells of the suppressor/cytotoxic phenotype carrying the Leu-2a antigen was significantly lower in the IA than in all other groups. In the IA + C group, the proportions of Leu-3a/3b and Leu-2a positive T lymphocytes returned to normal, although the patients still exhibited asthmatic symptoms. These findings suggest that cellular immunologic factors might be involved in the pathogenesis of intrinsic asthma.     

Lymphocyte transformation in extrinsic bronchial asthma

Lymphocytes from sixteen patients with extrinsic bronchial asthma and sixteen normal were investigated for their in vitro reactivity to stimulation with phytohaemagglutinin (PHA) and concanavalin A (Con A). No significant differences in maximum lymphocyte responses to PHA or Con A, either in the presence of foetal calf serum or autologous plasma, were found. The significance of these results in relation to T suppressor cell control of IgE formation is discussed.     

Intrinsic and extrinsic negative regulators of nuclear protein transport processes

The nuclear-cytoplasmic protein transport is a critical process in cellular events. The identification of transport signals (nuclear localization signal and nuclear export signal) and their receptors has facilitated our understanding of this expanding field. Nuclear transport must be appropriately regulated to deliver proteins through the nuclear pore when their functions are required in the nucleus, and to export them into the cytoplasm when they are not needed in the nucleus. Altered nuclear transport processes have been observed in stressed cells, which would change gene expressions. Some viruses interfere with nuclear transport in host cells to evade immune defense. Moreover, certain transport factors negatively regulate nuclear protein transport in cells. Understanding the regulatory mechanisms of nuclear-cytoplasmic trafficking not only provides important information about cellular processes, but also is of use for developing specific inhibitors for transport pathways.     

Intrinsic asthma and bacterial histamine release

In this study of intrinsic asthma (IA) in children the pathogenic role of bacteria in respiratory disease was elucidated by a basophil histamine liberation technique. Several strains of bacteria caused release of histamine from peripheral leukocytesin vitro. Normal, non-infectious and non-atopic children frequently responded in a similar fashion, although positive responses were less frequent. It seems that two different mechanisms of bacterial histamine release exist: interaction with the basophil-bound IgE and a direct interaction with the cell surface. It is suggested that the histamine release takes place only in the lung of IA patients, where a defective pulmonary barrier could permit the bacteria to enter, but not in healthy individuals.     

Soluble CD23 (sCD23) serum levels and lymphocyte subpopulations in peripheral blood in rhinitis and extrinsic and intrinsic asthma

To determine serum levels of IgE and sCD23 and lymphocyte subpopulations, we studied 37 control subjects and 84 patients (27 with allergic rhinitis, 27 with extrinsic asthma, and 30 with intrinsic asthma). A rise in surface CD23 on B and monocyte cells and sCD23 serum levels was exhibited by patients with rhinitis and extrinsic asthma. Unexpectedly, in intrinsic asthmatic patients, high CD23 expression on monocytes and high sCD23 levels were seen that did not result in IgE production. It appears that CD23, in its soluble form, could be a good disease marker, especially in asthma. Atopic patients yielded a significantly lower proportion of CD4⁺ T cells than intrinsic asthmatic patients and normal persons. Otherwise, CD4⁺ CD29⁺ CD45RA - and CD4⁺ CD29 – CD45RA ⁺ T-cell subsets were significantly decreased in all patient groups.     

Intrinsic and extrinsic light responses in melanopsin-expressing ganglion cells during mouse development

Melanopsin (Opn4) is a photopigment found in a subset of retinal ganglion cells (RGCs) that project to various brain areas. These neurons are intrinsically photosensitive (ipRGCs) and are implicated in nonimage-forming responses to environmental light such as the pupillary light reflex and circadian entrainment. Recent evidence indicates that ipRGCs respond to light at birth, but questions remain as to whether and when they undergo significant functional changes. We used bacterial artificial chromosome transgenesis to engineer a mouse line in which enhanced green fluorescent protein (EGFP) is expressed under the control of the melanopsin promoter. Double immunolabeling for EGFP and melanopsin demonstrates their colocalization in ganglion cells of mutant mouse retinas. Electrophysiological recordings of ipRGCs in neonatal mice (postnatal day 0 [P0] to P7) demonstrated that these cells responded to light with small and sluggish depolarization. However, starting at P11 we observed ipRGCs that responded to light with a larger and faster onset (<1 s) and offset (<1 s) depolarization. These faster, larger depolarizations were observed in most ipRGCs by early adult ages. However, on application of a cocktail of synaptic blockers, we found that all cells responded to light with slow onset (>2.5 s) and offset (>10 s) depolarization, revealing the intrinsic, melanopsin-mediated light responses. The extrinsic, cone/rod influence on ipRGCs correlates with their extensive dendritic stratification in the inner plexiform layer. Collectively, these results demonstrate that ipRGCs make use of melanopsin for phototransduction before eye opening and that these cells further integrate signals derived from the outer retina as the retina matures.     

Intrinsic versus extrinsic determinants during the development of Purkinje cell dendrites

The peculiar shape and disposition of Purkinje cell (PC) dendrites, planar and highly branched, offers an optimal model to analyze cellular and molecular regulators for the acquisition of neuronal dendritic trees. During the first 2 weeks after the end of the proliferation period, PCs undergo a 2-phase remodeling process of their dendrites. The first phase consists in the complete retraction of the primitive but extensive dendritic tree, together with the formation of multiple filopodia-like processes arising from the cell body. In the second phase, there is a progressive disappearance of the somatic processes along with rapid growth and branching of the mature dendrite. Mature Purkinje cell dendrites bear two types of spiny protrusions, named spine and thorn. The spines are numerous, elongated, located at the distal dendritic compartment and form synapses with parallel fibers, whereas the thorns are shorter, rounded, emerge from the proximal compartment and synapse with climbing fibers.     

Peripheral eosinophil counts as a marker of disease activity in intrinsic and extrinsic asthma

Background: Recently it has been suggested that the bronchospasm and hyperresponsiveness phenomena observed in asthma are secondary to the actions of the eosinophils; the purpose of this study was to evaluate the relationship between the peripheral number of eosinophils and various markers of disease activity in a group of asthmatics examined in childhood (mean age 10 years) and early adulthood (mean age 21 years). Methods: The relationship between eosinophil count and pulmonary function (FEV₁), respiratory symptoms, bronchial responsiveness to histamine and diurnal variation in peak expiratory flow rate (PEF) was studied in 70 subjects with bronchial asthma, of whom 24 had intrinsic and 46 extrinsic asthma. Self-reported symptoms of asthma were graded on a scale from 0 to 5, where 0 = no symptoms within the preceding 12 months and 5 = daily including nocturnal symptoms, and histamine responsiveness was analysed by means of the dose-response slope (DRS). Results: In both childhood and adulthood, a direct correlation was found between blood eosinophil count and symptom score (r= 0.69, P< 0.001 and r= 0.58, P < 0.001, respectively), whereas inverse correlations were observed between number of eosinophils and FEV, % predicted (r= .0.75, P < 0.001 and r= 0.80, P < 0.001. respectively). Furthermore, in adulthood, eosinophil count was found to be significantly correlated to hisiamine responsiveness (log DRS) (r= 0.65, P < 0.001) and diurnal PEF variation (r= 0.81, P < 0.001); these correlations were also noted after dividing the subjects into intrinsic and extrinic asthmatics. In both groups of subjects a significant inverse correlation was also found between histamine responsiveness and pre challenge FEV₁% predicted. The eosinophil count in childhood was weakly correlated to the symptom score in adulthood (r= 0.29, P < 0.02). Conlusions: This study showed a relationship between eosinophil count and seventy of asthmatic symptoms, level of pulmonary function, histamine responsiveness and diurnal variation in PEF in both intrinsic and extrinsic asthma; suggesting that the peripheral eosinophil count reflects asthmatic activity, and possibly the degree of inflammation in the airways, in both children and adults. Furthermore, a low number of eosinophils in childhood might be related to a relatively favourable prognosis with regard to symptoms of asthma in early adulthood.     

A cellular abnormality in glucocorticoid resistant asthma.

Peripheral blood mononuclear cells from asthmatic patients were cultured in soft agar with or without the synthetic glucocorticoid methylprednisolone (MP). The resulting colonies consisted mostly of T lymphocytes but included monocytes, often in a central position. Colony growth from patients whose asthma had responded satisfactorily to glucocorticoid medication was inhibited by MP in vitro at concentrations as low as 10(-9) M, and the ratio of helper to suppressor/cytotoxic T cells was reduced relative to untreated cultures. In contrast, patients shown to be resistant to the therapeutic effects of glucocorticoids yield colonies which differed little in number, size or constituent phenotype, whether untreated or exposed to MP at concentrations as high as 10(-8) M. Higher concentrations inhibited colony growth from both types of patient. Hybrid colonies were generated from partially purified cells from pairs of patients: monocytes from one member and lymphocytes from the other. The steroid sensitivity of these colonies was found to be dependent upon the source of the monocytes and not the lymphocytes. The results support the view that, in glucocorticoid resistant asthma, there is a defect in monocyte responsiveness to the hormone. This defect could explain the poor therapeutic effect of glucocorticoids in these patients. The results suggest that monocyte factors may be of importance in the pathogenesis of asthma in general.     

Intrinsic and extrinsic control of effector T cell survival and memory T cell development

Following infection or vaccination T cells expand exponentially and differentiate into effector T cells in order to control infection and coordinate the multiple effector arms of the immune system. Soon after this expansion, the majority of antigen-specific T cells die to reattain homeostasis and a small pool of memory T cells forms to provide long-term immunity to subsequent re-infection. Our understanding of how this process is controlled has improved considerably over the recent years, but many questions remain outstanding. This review focuses on the recent advancements in this area with an emphasis on how the contraction of activated T cells is coordinately regulated by a combination of factors extrinsic and intrinsic to the activated T cells.     

Intrinsic asthma and bacterial histamine release via lectin effect

Bacteria-induced histamine release from basophil leukocytes was observedin vitro in both children with intrinsic asthma (IA) as well as in normal individuals.In vivo the release is suggested to take place only in the lung of IA patients, where a defective pulmonary barrier would permit the bacteria to enter, but not in healthy individuals. The study indicates that two different mechanisms of bacterial histamine release might exist, an IgE-mediated reaction and a non-immunological mechanism consisting of a direct interaction with the basophil cell surface. The non-allergic mechanism might depend on a lectin effect where bacterial surface lectins interact with the basophil cell surface leading to release of histamine. Inhibition studies with carbohydrates suggest a multi-lectin reaction in the bacterial histamine release involving several types of lectins on the bacterial membrane reacting with different carbohydrate moieties on the cell surface of basophil leukocytes.