Age, experience and the changing brain.

In this review, various aspects of how environmental experience effects the structure of the cortex at different times in the age of the animal are summarized. The interactions of brain injury and sex on the age-dependent plastic changes in the cortex are also considered. Finally, we have attempted to reach some general conclusions that describe the effects of age, experience, sex, and injury on the cortex.

Blockade of basic fibroblast growth factor retards recovery from motor cortex injury in rats.

The endogenous expression of basic fibroblast growth factor (bFGF) was blocked by neutralizing antibodies following unilateral suction lesions of the motor cortex. Rats with control treatment (saline, goat IgG) after motor cortex lesions showed slow recovery of forelimb manipulatory abilities. Rats with blockade of bFGF expression showed little recovery. Anatomically, the control-treated lesioned rats showed an acute increase in bFGF and glial fibrillary acidic protein (GFAP) reactivity, and chronically they had normal dendritic arborization and spine density in layer V pyramidal cells in the remaining motor cortex. In contrast, rats treated with antibodies to bFGF showed little bFGF reactivity, normal GFAP reactivity, and atrophy of dendritic arbor and decreased spine density in layer V pyramidal cells. These results demonstrate the importance of endogenous bFGF release in processes related to functional recovery after cortical injury.

A subclass IgG4-specific antigen-binding radioimmunoassay (RIA): comparison between IgG and IgG4 antibodies to food and inhaled antigens in adult atopic dermatitis after desensitization treatment and during development of antibody responses in children.

A liquid-phase, antigen-binding radioimmunoassay measuring subclass IgG4 antibody (ab) to allergens has been developed. This assay, which uses monoclonal anti-IgG4 to bind IgG4, allows direct comparison of class (IgG)- and subclass (IgG4)-specific ab levels. These assays used radiolabeled purified allergens, Der p I (Ag P1) from the dust mite Dermatophagoides pteronyssinus, Lol p I (Rye 1), from ryegrass pollen, hen's egg ovalbumin, and beta-lactoglobulin from cow's milk. We have investigated IgG4 abs in several clinical situations. The results confirm that IgG ab responses to both inhalants and food proteins unequivocally include IgG4 ab. On average, the proportion of IgG4 ab to these antigens is far higher than the contribution of IgG4 to total IgG. In patients with adult atopic dermatitis, levels of both class and subclass ab were higher than in control subjects; however, the ratio of IgG4:IgG varied widely in patients and control subjects. During desensitization treatment of patients with perennial rhinitis, levels of IgG4 ab to Der p 1 increased sharply, but there were also increases in the total IgG ab responses so that the percentage contribution of IgG4 was only moderately increased (mean values: before, 29%; after, 36%). In a prospective study of children from atopic families, IgG4 abs to food proteins were detectable as early as 3 months. IgG abs to hen's egg ovalbumin and beta-lactoglobulin from cow's milk increased to a maximum at 3 years and declined by 5 years. However, specific IgG4 as a percentage of specific IgG increased progressively from a mean value of approximately 15% at 6 months to approximately 50% at 5 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of skin reactivity and specific antibody to egg and milk proteins in patients with atopic dermatitis: comparison with responses to the house dust mite antigen.

Sixty patients with atopic dermatitis attending an allergy clinic were assessed for evidence of skin sensitivity and serum antibodies to egg and milk proteins. Prick skin test responses to egg were found in 23 patients and in 74% of these positive egg radioallergosorbent test (RAST) was demonstrable. Positive prick test for milk were present in 10 patients, but only 30% gave a positive milk RAST. Quantitative intradermal skin testing, RAST, and a double antibody antigen binding radioimmunoassay confirmed the presence of IgE antibody to egg proteins but indicated that the levels were very low when compared to those seen to the house dust mite antigen in sensitive patients. In contrast, IgG antibody to purified egg and milk proteins was present in large amount in most patients, the levels being significantly higher than in non-allergic controls.

Development of IgE and IgG antibodies to food and inhalant allergens in children at risk of allergic disease.

In a prospective study of 92 children with at least one atopic parent, the development of the specific antibody responses to food and inhalant allergens during the first 5 years of life were assessed. By the radioallergosorbent test egg specific IgE antibody occurred in about 30% of the children with the mean peak concentration at 12 months. By the second year the prevalence of this antibody had increased whereas the mean concentration had decreased. Milk specific IgE antibody could not be shown in any subject, including four whose skin tests yielded positive results. Food specific IgG antibody was noted by antigen binding radioimmunoassays at 3 months in most children. These responses had peaked and began to fall by the fifth year. In contrast few children had detectable IgE or IgG antibody to inhalant allergens before the first 2 years of life. Both the concentration and prevalence of specific antibody, however, increased from the second to the fifth year and was greater in children whose skin tests yielded positive results. Breast feeding was associated with an increase in the prevalence of positive results from skin tests but was not associated with detectable IgE antibody to both food proteins, a lower concentration of IgG antibody to cows' milk, and was not associated with protection against the development of disease. A high level of exposure to dust mite was associated with an increased prevalence of positive results from skin tests to dust mite and appreciably higher antibody concentration. This study indicates differences in the humoral responses to food and inhalant allergens. Environmental factors appear to influence the development of these responses.

The relevance of inhalant and food allergens to the etiology and management of patients with atopic dermatitis.

Patients with atopic dermatitis have IgE antibodies to common environmental antigens, both foods and inhalants. Such antibodies are probably relevant and exposure to the corresponding antigens can give rise to eczema. Nevertheless, the mechanisms involved and the role of other etiologies, e.g. contact reactions, remain to be elucidated. Patients with atopic dermatitis should have comprehensive evaluations to determine the role of environmental antigens.

Cutaneous basophil hypersensitivity to inhalant allergens in atopic dermatitis patients: elicitation of delayed responses containing basophils following local transfer of immune serum but not IgE antibody.

Inhalant allergens applied to the skin of sensitive atopic dermatitis patients by means of a modified patch test technique, induce acute eczematous lesions. These lesions contain basophils, eosinophils, mononuclear cells, and neutrophils and represent an example of human cutaneous basophil hypersensitivity. The role of IgE antibody in this eczematous reaction was studied by systemic and local passive transfer experiments. Plasma with high IgE antibody when infused into patients with hypogammaglobulinemia as part of their replacement treatment resulted, post infusion, in cutaneous mast cell and blood basophil sensitization as measured by quantitative skin testing and leukocyte histamine release. Subsequent patch tests on these patients using the house dust mite antigen, antigen P1, produced macroscopic erythematous responses containing mononuclear cells, and eosinophils but not basophils. Local transfer of atopic dermatitis serum with high IgE antibody produced weak macroscopic responses and in these lesions mononuclear cells and both basophils and eosinophils were present. The serum activity which allowed transfer of basophil and eosinophil recruitment was heat labile. Specifically purified antibody to the mite antigen P1 (containing IgE and IgG antibody), when transferred, allowed eosinophil but not basophil recruitment to patch test sites. These results suggest that while the allergen-induced patch test response may involve IgE antibodies, as well as the cells normally involved in delayed responses, another serum activity is also involved.

A study of inactivation of Chlamydia trachomatis by normal human serum.

To assess the effect of human serum on the viability of Chlamydia trachomatis, organisms were mixed with unheated and heat inactivated homologous serum, and the numbers surviving after incubation at 37 degrees C for 1 hour were compared. With a pool of sera obtained from 12 donors, the number of chlamydiae surviving incubation in unheated serum was less than 1% of that surviving incubation in heat inactivated serum. The antichlamydial activity of the unheated pooled serum samples could be noticeably reduced by treatment with Mg-EGTA (ethyleneglycolbis (beta-amino ethyl ether)-N,N'-tetra-acetic acid). This indicated a requirement for calcium ions and showed that the alternative pathway of complement activation played only a minor role, if any, in the inactivation process. When 12 serum samples were tested individually it was found that four inactivated chlamydiae to an extent comparable with that seen with the pooled serum. The other eight samples showed only moderate (or slight) antichlamydial activity, with survival rates in unheated serum of 20-60% (or more than 60%) of those in heat inactivated serum. There was no correlation between the titres of antichlamydial antibodies and antichlamydial activity, all serum samples having undetectable or low concentrations of antibody on measurement by micro-immunofluorescence. The antichlamydial activity destroyed by heating was restored, however, when heat inactivated serum was mixed with an equal volume of an unheated serum that was not inhibitory to chlamydiae. When the latter serum was heated before addition antichlamydial activity was not restored, indicating the requirement of both a heat stable and a heat labile factor. This observation and the need for calcium ions for inactivation of chlamydiae are compatable with killing mediated by antibody and complement. Thus serum samples from individuals with no clinical or serological evidence of infection with chlamydiae vary in their ability to inactivate the organism, some having antichlamydial activity which is possibly mediated by antibody and complement.

Quantitative assessments of IgG and IgE antibodies to inhalant allergens in patients with atopic dermatitis.

Using antigen-binding radioimmunoassays, we have measured class specific antibodies against two major inhalant allergens, antigen P1 from D. pteronyssinus and Rye I from grass pollen, in sera from 69 patients with atopic dermatitis. The results show that many of the patients have IgE ab to these allergens in keeping with their skin tests. In all cases, the IgE ab was paralleled by IgG ab to the same allergen. In many sera, IgE ab to these inhalant allergens made a significant contribution to the total serum IgE. With two other allergens to which these patients had not been exposed, specific IgE ab was detected in only one serum, whereas the 42 sera tested did not contain IgE ab to diphtheria toxin. Eleven of the adult patients with atopic dermatitis had no history of asthma and had strongly positive skin tests. This group of patients had levels of total IgE and specific ab to antigen P1 that were very similar to those found in a comparable group of patients who had both atopic dermatitis and asthma. Our recent finding that allergens applied to the skin can induce delayed eczematous lesions provides a mechanism by which allergens could contribute to skin lesions. Our present results support the view that specific sensitivity to common allergens should be taken into account in considering the causes of these patients' skin lesions.