How often can the clinical diagnosis of exanthema subitum be confirmed with the HHV-6 serology test

Three years ago a newly recognized human herpes virus (HHV-6) was identified to be the causative agent for exanthem subitum (roseola infantum). So far this diagnosis was suggested chiefly by excluding other infections and the presence of a typical course of the disease. To find out how often the clinical diagnosis can be confirmed serologically, we asked five pediatricians in private practice as well as residents of the out-patient and infant departments of our hospital to obtain paired heparinized blood samples of any child suspicious for exanthem subitum. 36 children with clinically suspected exanthem subitum and a mean age of 14.2 (5-71) months were included in this prospective study. Indirect immunofluorescence was used to detect IgG and IgM antibodies to HHV-6. In 22 children (61%) the clinical diagnosis was confirmed serologically. IgM antibody was found in only 16 of these 22 children. In 8 patients the results were ambiguous. Three had in the same time a doubtful seroconversion to other viruses of the herpes group (HSV twice; EBV once), in four children there was an insufficient rise in IgG antibodies without presence of an IgM response, and once we found a very high HHV-6 specific antibody titre (greater than 1:80) in both serum samples. In 6 children neither a seroconversion nor a rise in HHV-6 antibody titre were found. Retrospectively, only three of these children had a clinical course really typical for exanthem subitum. We conclude that in most cases the clinical diagnosis of exanthem subitum will be confirmed by serological examination.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distribution of repetitive and non-repetitive circumsporozoite protein epitopes on Plasmodium falciparum sporozoites and immunochemical characterization of human malaria antisera.

The presence and distribution of circumsporozoite protein (CSP) epitopes located in the repetitive and non-repetitive regions were studied in three Plasmodium falciparum strains, NF54, IFA5 and IFA6. It was found by immunofluorescence, Western blotting and immunoelectron microscopy that mAbs to epitopes of the repetitive domaine bound similarly to the CSP of all three strains. MAbs to epitopes of the flanking regions yielded either some strain differences (mAbs to the C-terminal end), or reacted only in immunofluorescence tests on whole sporozoites (mAbs to the N-terminal end). Human sera from an area endemic for malaria, two of them positive in ELISA on (NANP)40 and two negative, were tested for their reactivity with epitopes of the flanking regions of the CSP. The presence of antibodies to such epitopes could be demonstrated by Western blots and immunocytochemistry independent of the reactivity of the sera to recognize (NANP)40. All tested bound to salivary gland tissues but not to their secretory product in immunocytochemical experiments.     

Low urinary calcium excretion in Bartter's syndrome

The urinary calcium excretion has been determined in 19 patients with Bartter's syndrome and found to be significantly lower than the calcium excretion in 92 healthy subjects (1.16 +/- 0.82 vs. 4.36 +/- 2.71 mmol/24 h, p less than 0.001). There were no differences in height, weight, glomerular filtration rate, urinary sodium excretion or serum calcium concentration between the patients and the control subjects to account for the disparity in calcium excretion. In the patients, the concentrations for ionized calcium, PTH, 25-OH vitamin D and 1,25-(OH)2 vitamin D were normal. A low urinary calcium excretion appears to be a characteristic feature of Bartter's syndrome. The cause remains unexplained.     

Prolapse of the urethral mucosa in girls

In the recent 9 years 39 girls aged from 2 to 10 years were treated at the clinic for prolapse of the urethral mucosa. Among them 24 had circular and 15 had segmental prolapse. The disease was encountered most frequently between 6 and 10 years of age, predominantly in the summer. Complex treatment was started with nonoperative measures which were followed by operation if the prolapse persisted or recurred. Spontaneous reduction of the mucosa occurred in 6 of 22 children who were treated by nonoperative measures, in 3 cases the effect was temporary and a recurrence developed. Operative excision of the mucosa was carried out in 36 girls. The results were good. The article discusses the etiopathogenesis of the disease and analyses the morphological changes in the removed urethral mucosa.     

The pharmacological stimulation of NMDA receptors via co-agonist site: an fMRI study in the rat brain

d-Serine has been proposed as an endogenous modulator at the co-agonist glycine-binding site of N-methyl-d-aspartate (NMDA) receptors. There is still some debate as to whether this site is saturated in vivo, but it seems likely that this depends on regional differences in local glycine or d-serine concentrations. In order to identify areas where the co-agonist site was not fully activated in vivo, we studied the effect of intraperitoneal d-serine administration in the rat brain using functional magnetic resonance imaging (fMRI). Using contrast agent injection, the variations in the relative cerebral blood volume (CBVrel) in several regions of interest were evaluated. d-Serine (50 mg/kg) elicited a significant statistical increase in the CBVrel in the hippocampus. This effect was inhibited by the specific full antagonist of the co-agonist glycine site L-701,324 indicating that the hippocampal activation occurred through the binding of the agonist d-serine to the glycine-binding site of NMDA receptors. This result demonstrates that in the hippocampus, the co-agonist sites of NMDA receptors are not endogenously saturated under our experimental conditions, suggesting an important role of d-serine in the modulation of receptor function in the hippocampus.     

Allergen extracts directly mobilize and activate human eosinophils

Allergic diseases are characterized by the presence of eosinophils, which are recruited to the affected tissues by chemoattractants produced by T cells, mast cells and epithelium. Our objective was to evaluate if allergens can directly activate human eosinophils. The capacity of purified allergen extracts to elicit eosinophil chemotaxis, respiratory burst, degranulation and up-regulation of the adhesion molecule complement receptor 3 (CR3) was determined in eosinophils isolated from healthy blood donors. Eosinophils stimulated with an extract from house dust mite (HDM) released the granule protein major basic protein (MBP) and up-regulated the surface expression of CR3. Cat allergen extracts also induced the up-regulation of CR3, but not the release of MBP; instead cat, as well as birch and grass allergens, elicited the release of eosinophil peroxidase (EPO). In addition, grass pollen extract caused the secretion of MBP. None of the allergens stimulated eosinophilic cationic protein release, nor production of free oxygen radicals. Both HDM and birch extracts were chemotactic for eosinophils. These findings establish that common aeroallergens can directly activate eosinophils in vitro. We propose that eosinophil activation in vivo is not exclusively mediated by cytokines and chemokines of the allergic inflammatory reaction, but could partly be the result of direct interaction between allergens and eosinophils.     

Interferon-γ is essential for the development of cerebral malaria

Infection with Plasmodium berghei ANKA (PbA) causes fatal cerebral malaria (CM). While a pathogenic role for tumor necrosis factor (TNF) has been established, we asked whether a disruption of interferon-γ (IFN-γ) signaling would modulate CM. We demonstrate here that IFN-γR-deficient mice are completely protected from CM. PbA-induced release of TNF and up-regulation of endothelial intercellular adhesion molecule (ICAM)-1 expression, recruitment of mononuclear cells, and cerebral microvascular damage with vascular leakage occur only in wild-type mice. Protected mice die at a later time of severe anemia and overwhelming parasitemia. Resistance to CM in IFN-γR-deficient mice is associated with reduced serum TNF levels, reduced interleukin-12 expression in the brain and increased T-helper 2 cytokines. In conclusion, IFN-γ is apparently required for PbA-induced endothelial ICAM-1 up-regulation and subsequent microvascular pathology, resulting in fatal CM. In the absence of IFN-γ signaling, ICAM-1 and TNF up-regulation is reduced; hence, PbA infection fails to cause fatal CM.     

Mucosal FOXP3-expressing CD4+ CD25high regulatory T cells in Helicobacter pylori-infected patients

Helicobacter pylori chronically colonizes the stomach and duodenum and causes peptic ulcers or gastric adenocarcinoma in 10 to 20% of infected individuals. We hypothesize that the inability of patients to clear H. pylori infections is a consequence of active suppression of the immune response. Here we show that H. pylori-infected individuals have increased frequencies of CD4(+) CD25(high) T cells in both the stomach and duodenal mucosa compared to uninfected controls. These cells have the phenotype of regulatory T cells, as they express FOXP3, a key gene for the development and function of regulatory T cells, as well as high levels of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) protein. In contrast, mucosal CD4(+) CD25(low) and CD4(+) CD25(-) cells express little FOXP3 mRNA and low levels of the CTLA-4 protein. Mucosal CD4(+) CD25(high) T cells are present in individuals with asymptomatic H. pylori infections as well as in duodenal ulcer patients. The frequencies of CD4(+) CD25(high) cells are also increased in the stomachs of H. pylori-infected patients with gastric adenocarcinoma, particularly in cancer-affected tissues. These findings suggest that regulatory T cells may suppress mucosal immune responses and thereby contribute to the persistence of H. pylori infections.