Expression of CD35 (CR1) and CD11b (CR3) on circulating neutrophils and eosinophils from allergic asthmatic children

Complement receptors on neutrophils and eosinophils play a role in activation and adhesion. During asthmatic reactions these receptors have been found elevated on circulating granulocytes. In the present study we compared the expression of CD35 (complement receptor type 1) and CD11b (complement receptor type 3) on neutrophils and eosinophils from asthmatic and non-asthmatic children. This was done in whole blood samples using depolarized light scattering for the discrimination of neutrophils and eosinophils. The non-stimulated expression as well as the upregulated expression of receptors by the chemotactic peptide N-formylmethionyl-leucyl-phenyl-alanine (fMLP) were studied. The results showed that without prior stimulation only the expression of CD35 on neutrophils was significantly elevated in children with asthma (P<0.05). After up-regulation with fMLP, the CD11b expression on neutrophils (P<0.005, fMLP: 0.002 microM) and eosinophils (P<0.05, fMLP: 0.02 microM) was significantly higher in asthmatic children than in the controls. These results indicate that the inducible expression of CD11b on neutrophils and eosinophils from allergic asthmatic children is primed in vivo.     

Risk Factors for a First Febrile Seizure: A Matched Case-Control Study

Summary We conducted a matched casecontrol study to identify risk factors for first febrile seizures, with special emphasis on characteristics of the acute illness episode. Cases were identified through hospital emergency departments; controls were identified through outpatient clinics and emergency departments. Sixtynine children with first febrile seizures and no history of previous unprovoked seizures were matched for age (±6 months), site of routine pediatric care, and date of visit (±weeks) with 1 or 2 febrile controls who had no history of previous febrile or unprovoked seizures. Medical records for the index visit were reviewed, and parents were interviewed by telephone. Illness characteristics examined included height of temperature, type of underlying illness, contact with a physician during the illness but before the index visit, and use of acetaminophen or decongestants. Family history of febrile and of unprovoked seizures, sociodemographic characteristics, daycare use, and selected preand perinatal variables were also studied. On multivariable analysis, significant independent risk factors were height of temperature, history of febrile seizures in a firstor in a higher degree relative. Gastroenteritis as the underlying illness had a significant inverse (i.e., protective) association with febrile seizures. Maternal smoking during pregnancy was a marginally significant predictor of febrile seizures.     

Isoquinoline Derivatives Isolated from the Fruit of Annona muricata as 5-HTergic 5-HT1A Receptor Agonists in Rats: Unexploited Antidepressive (Lead) Products

The fruit and the leaves of Annona muricata (Annonaceae) are used in traditional medicine for their tranquillizing and sedative properties. Extracts of the plant have been shown to inhibit binding of [³H]rauwolscine to 5-HTergic 5-HT_1A receptors in calf hippocampus, and three alkaloids, annonaine ( 1 ), nornuciferine ( 2 ) and asimilobine ( 3 ), isolated from the fruit have been shown to have IC50 values of 3 μm , 9 μm and 5 μm , respectively, although in ligand-binding studies it was not possible to determine whether interaction of these ligands with the receptor was agonistic or antagonistic. This paper presents the results of functional assays of the alkaloids. The inhibition of cAMP accumulation was tested in NIH-3T3 cells stably transfected with the 5-HT_1A receptor from man. None of the alkaloids showed antagonistic properties towards the 5-HT_1A receptors because in the antagonistic tests no influence on the forskolin-stimulated increase of cAMP level was detected. Full agonistic properties were measured for all three compounds; the inhibition constants (K_i) for 1, 2 and 3 were < 10 μm . Inhibition of the binding of the radioligand to the 5-HT_1A receptor was observed in every ligand-binding assay performed with the alkaloids; the K_i values for 1, 2 and 3 were in the μm range. These results imply that the fruit of Annona muricata possesses anti-depressive effects, possibly induced by compounds 1, 2 and 3 , and that in the past potent leads for the development of anti-depressive therapeutics have not been used.     

Regulation of CD59 expression on K562 cells: effects of phorbol myristate acetate, cross-linking antibody and non-lethal complement attack.

CD59 is the major membrane attack complex of complement (MAC) inhibiting protein on human cells. Its regulation is therefore an important factor in determining the fate of cells at sites of complement activation. We have chosen the K562 erythroleukaemia cell line as a model for studies of the regulation of CD59 expression, because it has previously been reported that phorbol 12-myristate 13-acetate (PMA) caused a 15-fold up-regulation of CD59 mRNA in these cells, implying a substantial capacity for CD59 synthesis. However, no assessment of CD59 protein expression was made in these studies. We show here that surface expression of CD59, as assessed by flow cytometry, was increased four-fold over a 16-hr incubation with PMA, whereas surface expression of decay-accelerating factor (DAF) (CD55) and membrane cofactor protein (MCP) (CD46) was not altered. The newly expressed CD59 was functionally active and anchored through glycosyl-phosphatidylinositol (GPI). Increased expression was dependent upon de novo protein synthesis. CD59 released into cell supernatant was also increased seven-fold by PMA, this 'secreted' CD59 retained its GPI anchor. Non-lethal complement attack did not alter CD59 expression but antibody cross-linking of CD59 caused a rapid loss of the CD59-antibody complexes. However, CD59 was quickly restored to pre-attack levels. This rapid restoration was not dependent upon protein synthesis, suggesting release from preformed stores.     

Nutrition and aging: nutritional status of "apparently healthy" elderly (Dutch nutrition surveillance system)

In a nationwide survey the nutritional status was assessed of 539 apparently healthy, independently living elderly aged 65-79 years. Anthropometric data showed no energy deficits. The prevalence of anemia was 4 and 1% among men and women, respectively. Many elderly showed a low level of 25-hydroxyvitamin D in plasma (less than 31 nmol/L: men 35%; women 43%), indicating a marginal status. Although the prevalence of low blood levels of folate, pyridoxal-5'-phosphate, and total carotenoids was higher among the elderly than among younger adults, clear (clinical) signs of nutritional deficiencies were not observed. Prevalence of obesity (13%), hypercholesterolemia (38%), and hypertension (63%) was found to be high, the percentages being higher for women than for men. Several indicators of the nutritional status appeared to differ among age groups. It is concluded that few differences can be considered as being due to physiological aging, which finding should be reflected in reference values for elderly people.     

Granular cell tumours of the lower respiratory tract

Granular cell tumours rarely involve the lower respiratory tract. We report eight cases surgically resected at our institution. There were four females and four males, aged between 18 to 56 years (mean 40). One tumour associated with a peripheral lung adenocarcinoma was asymptomatic. The other lesions presented with obstructive pneumonitis (3 cases), haemoptysis (2), dyspnea (1) or cough (1). These tumours were tracheal (1) or bronchial (6) and one case was located in the lung parenchyma. Four cases were multicentric with associated lesions located in a bronchus (2), the oesophagus (1) or a mediastinal lymph node (1). All tumours, with the largest diameter ranging from 0.5–4.5 cm, were histologically invasive. The tumours were positive for S-100 protein, neuron specific enolase, KP1 (CD68) and vimentin. No tumour expressed desmin, keratin or p53 oncoprotein. Our study demonstrates that, in spite of marked anatomical and clinical polymorphism, the rare granular cell tumours of the lower respiratory tract have a constant histological appearance. Our observations confirm that large tumours (> 8–10 mm) usually extend beyond the tracheo-bronchial cartilages and, therefore, only surgical treatment may avoid recurrence.     

Factors related to renal haemodynamics in young type-1 diabetes mellitus patients

The influence of metabolic control (HbA_1c), noradrenaline (NA) and insulin-like growth factors (IGF-I and IGF-II) on renal function and size was investigated in 11 insulin-dependent diabetes mellitus patients aged 11–17 years. Renal function was evaluated in terms of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Renal size was determined as renal parenchymal volume (RPV) by ultrasonography. The patients' HbA_1c values ranged from 8.2% to 12.9% (normal range 5.5–8.5%) and their GFR and ERPF were higher than normal. Their IGF-II values were higher, and NA and IGF-I levels were lower than those of healthy controls. Inverse correlations between NA and GFR (r=–0.66) and NA and ERPF (r=–0.63) were found. No correlation was found between serum IGF-I and renal functional parameters. The IGF-II values correlated with GFR and HbA_1c (r=0.63,r=0.70 respectively). There were linear correlations between RPV and GFR, RPV and ERPF, HbA_1c and GFR, and ERPF and RPV. Decreased NA concentrations and increased IGF-II values appear to be factors contributing to renal hyperfunction in these patients.