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Biomedical subjects

C H Rieger

Publications and source records attributed to C H Rieger.

At least 37 records · Page 2Linked to original sources

Increase in platelet count following short course therapy with recombinant alpha-2b-interferon in immune thrombocytopenic purpura in childhood.

Two boys, aged three and seven years with immune thrombocytopenic purpura continued to show platelet counts below 20,000/mm3 inspite of treatment with high dose gammaglobulin and steroids. Alpha-2b-interferon injections were followed by normalisation of platelet counts in both patients. No side effects were seen. Alpha-interferon may be a safe and effective treatment for childhood-ITP.

Child↗

Enhanced production of platelet activating factor by peripheral granulocytes from children with asthma.

Granulocytes from 23 asthmatic children aged 4-15 years and 32 age-matched healthy children were studied. Cells were purified by Dextran sedimentation and Percoll gradient centrifugation from heparinized blood. After in vitro stimulation by ionophore A23187 the amount of newly synthesized PAF and LTC4 was assessed by radio receptor assay or radioimmunoassay respectively. Eight patients had symptoms of asthma within the last 3 weeks before examination. Granulocytes from the symptomatic patients showed a significantly higher PAF generation (median 125 ng/10(6) cells, range 7-189 ng/10(6) cells) when compared to asymptomatic patients (p less than 0.001, median 14 ng/10(6) cells, range 6-33 ng/10(6) cells) or controls (p less than 0.001, median 11 ng/10(6) cells, range 3-26 ng/10(6) cells). In contrast, LTC4 generation was increased in both patient groups. The results suggest a regulatory role of PAF in the exacerbation of asthma.

Adolescent↗

SO2-induced enhancement of inhalative allergic sensitization: inhibition by anti-inflammatory treatment.

Epidemiological studies have shown a relationship between air pollution and allergic airway disease. In a previous study we have found that exposure to SO2 enhances allergic sensitization to inhaled ovalbumin (OA) in the guinea pig. We have now investigated the influence of pre-treatment with anti-inflammatory drugs on SO2-induced enhancement of allergic sensitization in this model. Four groups of 6 guinea pigs each were exposed to 5 ppm SO2 on 5 consecutive days over 8 h per day with intermittent inhalation of OA, while the air-control group was exposed to clean air and OA. During the period of SO2 exposure and sensitization three experimental groups were treated with indomethacin (group I), methylprednisolone (group M) and nebulized nedocromil sodium (group N), while the control group remained untreated. Guinea pigs were investigated for sensitization to OA by specific bronchial provocation tests using body plethysmographic measurement of compressed air (CA) and by measurement of specific antibody response in serum. While in the SO2-exposed control group 5 of 6 animals reacted to specific bronchial provocation testing (CA median 0.15 ml, range 0-0.175 ml), only 1 animal was sensitized in group M (CA 0 ml, 0-0.125, p < 0.05), whereas no bronchial reactions were seen in groups I and N (CA 0 ml, 0-0.05, p < 0.025). Specific IgG antibody titres increased in the control group (median 43 EU-->85 EU), but not in the treatment groups (medians group I 35 EU-->35 EU, group M 30-->35 EU, group N 64-->50 EU).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Coexpression of CD4 and CD8 on mitogen-activated peripheral blood T cells from children with asthma: possible involvement of interleukin 4.

Mononuclear cells were isolated from the peripheral blood of 28 asthmatic and 18 healthy children aged 3 to 16 years. The cells were stimulated with phytohemagglutinin for 96 hours. Activated cells were detected microscopically by MTT staining. Expression of cell surface antigens was detected by indirect immune fluorescence using CD4-specific and CD8-specific monoclonal antibodies. Results indicate an enhanced expression of CD8 on mitogen-activated T cells from asthmatic children compared with cells from healthy controls (median 43% versus 27%). Further experiments revealed that CD8 is coexpressed with CD4 on activated lymphocytes. Coexpression is significantly enhanced with lymphocytes from asthmatic patients compared with normal controls. In addition, interleukin 4 is able to enhance this coexpression with lymphocytes from healthy but not asthmatic children suggesting an in vivo preactivation of lymphocytes from asthmatic patients with interleukin 4.

Adolescent↗

T cell receptor gamma delta bearing cells are decreased in the peripheral blood of patients with atopic diseases.

The biological role of T cell receptor (TCR) gamma delta bearing cells is currently not fully understood. Recently, a monoclonal antibody (TCR delta 1) reacting against the whole molecule became available which facilitates the direct analysis of TCR-gamma delta+ cells. We studied 11 children with atopic dermatitis, 20 children with atopic asthma, 18 adults with atopic dermatitis and 38 healthy age matched controls aged 4-51 years. Lymphocytes were isolated from heparinized peripheral blood and the proportion of TCR-gamma delta+ lymphocytes was determined by FACS analysis. Patients with atopic diseases yielded a significantly (P less than 0.01) lower proportion of TCR-gamma delta+ cells compared with normal controls (median 4.8% versus 7.1%). The percentage of TCR-gamma delta+ cells showed an age-dependent decline in both the patient group (r = -0.49, P less than 0.01) and the control group (r = -0.40, P less than 0.01). In addition, the proportion of cells which expressed CD8, TCR-gamma delta or CD4, TCR-gamma delta simultaneously was determined by double labelling immunofluorescence. Whereas CD4+, TCR-gamma delta+ cells could be identified in only a few individuals, CD8+, TCR-gamma delta+ cells were found in nearly all controls (median 2.4%, range 0.0-10.8%); atopic patients displayed significantly (P less than 0.01) lower proportions of CD8+, TCR-gamma delta+ cells.

Adolescent↗

Imbalance of CD4+CD45R+ and CD4+CD29+ T helper cell subsets in patients with atopic diseases.

To evaluate the proportion of helper cell subsets we studied 18 children with atopic dermatitis, 30 patients with asthma, 27 healthy age-matched controls aged 1 to 17 years and 11 atopic controls without symptoms related to atopy, aged 9-22 years. Lymphocytes were isolated from heparinized peripheral blood and the proportion of CD4+CD29+ and CD4+CD45R+ cells was determined by double-labelling immunofluorescence. Children with atopic dermatitis yielded a significantly (P less than 0.01) higher proportion of CD4+CD45R+ (median 75%) cells compared with normal controls (median 66.6%), whereas the proportion of CD4+CD29+ cells was significantly (P less than 0.01) lower in patients with atopic dermatitis (median 20.4 versus 29.6%). Interestingly, the percentage of CD4+CD45R+ cells shows an age-dependent decline (r = -0.67, P less than 0.01) in the control group, which is not found in the patient group.

Adolescent↗

Breast feeding modifies production of SIgA cow's milk-antibodies in infants.

One hundred and fifty-eight healthy mature newborns were divided into 3 groups according to their risk of allergy: Group A, no risk (n = 62), group B, low risk (n = 30) and Group C, high risk (n = 66). Saliva was collected at birth and after 3 and 6 months. SIgA anti-casein and anti-beta-lactoglobulin were determined by a direct ELISA technique. The highest concentrations of secretory antibodies were measured after birth. After 3 months, breast fed infants had lower salivary SIgA anti-casein concentrations than the group receiving cow's milk (p less than 0.01). The effect of breast-feeding was seen even after a nursing period of only 3 weeks. Infants without risk of allergy fed cow's milk exclusively had higher SIgA anti-casein (p less than 0.03) and anti-beta-lactoglobulin concentrations than low risk infants at the age of 6 months. These data show a modifying effect of breast feeding on salivary SIgA production against cow's milk protein.

Animals↗

Enhanced superoxide generation by eosinophils from asthmatic children.

In 21 asthmatic children, aged 2-19 years, and 11 age-matched controls purified (purity greater than 75%) peripheral blood eosinophils and neutrophils (purity greater than 95%) were stimulated with phorbol myristate acetate (44 ng/ml) for 30 min at 37 degrees C. The superoxide generation was determined as well as the superoxide dismutase inhibitable cytochrome c reduction. Eosinophils obtained from asthmatic patients displayed a significantly higher O2- generation (p less than 0.01) when compared to neutrophils from the same patients or to eosinophils and neutrophils from healthy controls. Preincubation with human recombinant granulocyte macrophage colony stimulating factor for 30 min or platelet-activating factor for 10 min resulted in augmented O2- generation by eosinophils from control, but not from asthmatic children, indicating a possible in vivo priming of eosinophils in asthma.

Adolescent↗

Elevated concentrations of salivary secretory immunoglobulin A anti-cow's milk protein in newborns at risk of allergy.

Secretory immunoglobulin A (SIgA) anti-casein and SIgA anti-beta-lactoglobulin (BLG) were determined in the saliva of 158 healthy mature infants at birth and in breast milk samples using a direct Elisa technique. IgG anti-casein and anti-BLG were measured in serum samples from mothers and newborns (cord blood). A high risk of allergy was defined in 66 infants who had cord blood (CB)-IgE levels greater than or equal to 0.9 IU/ml and/or parents with atopic diseases. Thirty infants had CB levels less than 0.9 IU/ml and parents without clinical symptoms of atopy but with elevated serum IgE concentrations or type I skin reactions to common allergens (low risk). Sixty-two infants had CB-IgE levels less than 0.9 IU/ml and healthy parents (no risk). The groups were matched for social status, smoking and dietary habits. SIgA anti-casein and anti-BLG were detected in all newborns. SIgA anti-casein was significantly higher (p less than 0.05) in high risk infants (medium 157; 50% confidence limits 45-270) than in no risk (48; 25-150) or low risk infants (43; 21-130). SIgA anti-casein values correlated with maternal allergy, maternal allergy plus CB-IgE, but not with paternal allergy. Breast milk SIgA anti-BLG was depressed (p less than 0.05) in mothers with manifest allergy compared to healthy mothers. Determination of salivary SIgA anti-casein may represent an additional screening method for early detection of infants with atopic disposition.

Caseins↗

Relationship between LTC4 generation of hypodense eosinophils and bronchial hyperreactivity in asthmatic children.

In 19 asthmatic children aged 6-16 years, the degree of bronchial hyperreactivity was determined in relationship to the concentration of inhaled histamine which caused a fall of the specific conductance (sGaw) to 60% of the baseline value PC60sGaw. At the time of lung function testing, a sample of heparinized blood was obtained from each patient. Eosinophils were purified and separated into a normodense and hypodense fraction by Percoll gradient centrifugation. After in vitro stimulation by ionophore A 23187, the leukotriene C4 (LTC4) content was determined in the culture supernatants. Hypodense eosinophils of the 13 children with a histamine threshold lower than 1 mg/ml generated significantly (p less than 0.01) larger amounts of LTC4 (0.8-36.3 ng/10(6) cells) when compared to 6 children with a histamine threshold higher than 1 mg/ml (0.7-12.1 ng/10(6) cells) and 12 healthy controls (0.4-8.2 ng/10(6) cells). Preincubation of eosinophils with platelet activating factor (PAF) induced an enhanced LTC4 production, not only in hypodense cells from both asthmatic groups but also in normodense cells from patients with severe hyperresponsiveness. These results are consistent with other results which suggest an important role of eosinophils, their activation by PAF and enhanced release of spasmogenic LTC4 in the pathogenesis of asthma.

Adolescent↗

Detection of activated lymphocyte subsets by fluorescence and MTT staining.

A double staining technique for simultaneously determinating cell surface phenotype and the degree of cell activation is described. As an activation marker, the tetrazolium dye MTT has been used. Cells were incubated for 30 min with MTT. Activated cells yielded a granular staining pattern. Upon termination of the reaction with sodium azide, a double-step immunofluorescence staining procedure using monoclonal antibodies specific for cell surface antigens was performed. The percentage of cells simultaneously displaying MTT formation and fluorescence was microscopically evaluated. Our results demonstrate that MTT staining is expressed concomitantly with the IL-2 receptor and the transferrin receptor. This method permits a simple characterization of activated T cell subsets and can be used clinically to analyse the T cell functions of patients being treated with immunosuppressive agents and patients with acquired immune deficiency syndrome.

Acquired Immunodeficiency Syndrome↗

The DiGeorge sequence. II. Immunologic findings in partial and complete forms of the disorder.

We present immunological in vitro data on a group of 16 patients with the DiGeorge sequence (DGS). Detailed tests gave evidence that the decrease in number and function of mature T-cells is closely correlated with phenotypic expression and represents a wide immunological spectrum ranging from normal function to severe combined immunodeficiency with B-cells. Careful immunological testing in DGS may help to plan therapeutic procedures (i.e. thymic factor therapy or bone marrow transplantation), may also have prognostic significance and help to gain insight into mechanisms operative in disturbances of T-cell regulation.

Adenosine Deaminase↗

Transient hypogammaglobulinemia of infancy: Five new cases, review of the literature and redefinition.

The clinical and immunological data of 5 patients with transient h hypogammaglobulinemia of infancy (THI) are presented and compared to published data. In THI, there is distinction between patients who can mount a specific immune response, by producing specific antibodies to bovine serum albumin, diphtheria toxin, and isohemagglutinins, and patients with more severe forms of immunodeficiency. With only 5 reported cases of THI in 11 years and analysis of more than 8000 sera-, our data support the notion that THI is a relatively rare disorder. THI can only be diagnosed with certainty in retrospect, although the ability to mount an active, specific immune response is a strong indicator for the diagnosis. We propose a more accurate definition of THI to help avoid clinical misjudgement.

Agammaglobulinemia↗

Enhanced leukotriene C4 production by peripheral eosinophilic granulocytes from children with asthma.

Granulocytes and mononuclear cells were isolated from the blood of asthmatic and healthy children. Stimulation with ionophore A 23187 induced a significantly higher leukotriene C4 (LTC4) generation from granulocytes of asthmatic children than from granulocytes of healthy controls. In contrast, mononuclear cells from patients and controls did not differ in their ability to produce LTC4. Additional analysis showed that the difference in LTC4 generation of granulocytes was due to increased formation but not to decreased oxidative degradation of LTC4. Analysis of LTC4 generation of purified neutrophils and eosinophils revealed that LTC4 was generated almost exclusively by eosinophils and, in particular, the hypodense population. Granulocytes from patients with a history of severe asthma displayed a higher LTC4 formation than granulocytes from patients with less severe disease.

Adolescent↗

Bronchial sensitization in guinea pigs following ingestion of ovalbumin.

Local bronchial mucosal hypersensitivity following antigen feeding was studied in the guinea pig. Groups of 6 animals were fed 1% ovalbumin (OA) in tap water or tap water without antigen (control group) for different feeding periods (14, 28, 42, and 56 days). Inhalative provocations with increasing concentrations of OA (0.5-8% OA) were performed at the end of each feeding period followed by body plethysmographic measurement of airway obstruction. Specific bronchial hypersensitivity to inhaled OA was not found in the control group, whereas specific bronchial reactivity to OA, described as reactivity index, was significantly different from the control group after 14 (p less than 0.05), 28 (p less than 0.001) and 42 days (p less than 0.01) of feeding. No difference to the control group was found after 56 days of feeding. Anti-OA IgG total and IgG1 in serum and bronchoalveolar lavage fluid were increased in OA-fed animals reaching maximal concentrations at day 28 of the feeding period. We conclude that oral feeding of a 1% solution of OA can induce a transient state of local hypersensitivity to inhaled antigen in the guinea pig as manifested by bronchoconstriction on OA inhalation and increased concentrations of local and systemic specific antibodies. This period of local hypersensitivity is followed by tolerance.

Aerosols↗

Prematurity and maternal bronchial hyperresponsiveness.

Bronchial reactivity was compared among mothers of neonates with unexplained premature delivery and mothers of preterm neonates with known etiology of prematurity as well as mothers who delivered their children at term. Bronchial reactivity was measured by unspecific bronchial provocation testing with histamine. A significantly higher incidence of bronchial hyperreactivity was found among mothers with unexplained prematurity as compared to the control groups. An imbalance in the autonomic nerve system leading to prematurity as well as bronchial hyperresponsiveness is suggested.

Adult↗

[Effect of passive smoking on bronchial reactivity in school children].

Passive smoking on the part of children leads to an increase in the incidence of upper airway infections in early childhood, an elevated incidence of childhood asthma, and an aggravation of existing asthma. We investigated the bronchial reactivity of 80 healthy, symptom-free schoolchildren, 44 from smoking families (SF), 36 from non-smoking families (NF), employing treadmill exercise during which the subjects inhaled cooled air (-2 degrees C), and compared the results obtained with those found in a group of 27 children with asthma (A). A positive bronchial reaction (50 per cent Raw increase following exercise on the treadmill) was observed significantly more frequently in the SF group than in the NF group (22 out of 44 children as compared with 10 out of 36 children, p less than 0.05); both groups differed significantly from the group of asthmatics (21 out of 27 children). It is concluded that bronchial hyperreactivity occurs more frequently in clinically healthy, passively smoking children as compared with a control group.

Asthma↗