Preseasonal local allergoid immunotherapy to grass pollen in children: a double-blind, placebo-controlled, randomized trial

BACKGROUND: We assessed the efficacy of preseasonal local allergoid immunotherapy in a group of children with asthma and/or rhinitis and/or rhinoconjunctivitis due to grass pollen. METHODS: We randomly assigned 24 children allergic to grass pollen to receive local allergoid immunotherapy for 3 months before the pollen season and 24 such patients to receive identically appearing placebo. The immunotherapy consisted of tablets of monomeric allergoid grass pollen allergens held in the mouth until they dissolved and then swallowed. The study was double-blind. Symptoms and medications were scored on diary cards during the pollen season. Nasal eosinophil cationic protein levels were measured by the monoclonal antibodies EG1 and EG2 outside the pollen season and at low and at high pollen concentration during the pollen season. RESULTS: The active-treatment group had a statistically significant reduction of total symptoms (P<0.05), especially bronchial symptoms (P<0.05), in comparison with the placebo group. Immunotherapy was well tolerated and compliance was good. Nasal levels of EG2 and EG1 increased significantly during the pollen season, but there was no difference between groups. EG2/EG1 increased significantly only in the placebo group during natural allergen exposure (P<0.01). CONCLUSIONS: Our results suggest that this immunotherapy is effective for the treatment of asthma due to grass pollen in children.     

Haplotype analysis of BRCA1 gene reveals a new gene rearrangement: characterization of a 19.9 KBP deletion

Germ-line mutations in the BRCA1 gene cause hereditary predisposition to breast and ovarian cancer. BRCA1 and BRCA2 mutations account for about 40% of high-risk families. Mutation-screening methods generally focus on genomic DNA and are usually PCR based; they enable the detection of sequence alterations such as point mutations and small deletions and insertions. However, they do not allow the detection of partial or entire exon(s) loss, because the presence of the homologous allele results in a positive PCR signal, giving rise to a false-negative result. Identification of unusual haplotypes in patient samples by an expectation maximization algorithm has recently been suggested as a method for identifying hemizygous regions caused by large intragenic deletions. Using a similar approach, we identified a novel BRCA1 genomic rearrangement in a breast/ovarian cancer family negative at the first mutation screening; we detected a deletion encompassing exons 14-19, probably due to replication slippage between Alu sequences.     

Effects on inflammation parameters of a double-blind,placebo controlled one-year course of SLIT in children monosensitized to mites

BACKGROUND: Clinical documentation about effects on local markers of inflammation of sublingual immunotherapy (SLIT) in children is still poor. METHODS: Twenty-four children (age range 4-16 years, average 8.5 years) monosensitized to house dust mites (HDMs) were randomized to receive active or placebo SLIT for this allergen according to a double-blind, placebo-controlled design. Before treatment and 10-12 months later the following parameters were checked: ECP and tryptase in sputum and nasal secretion, serum and nasal mite-specific IgE (sIgE), allergen-specific nasal challenge test (sNCT), nasal symptoms and tryptase after sNCT. RESULTS: Nasal tryptase and nasal IgE in basal conditions were unchanged in treated children but significantly increased in untreated children (P = 0.0156 and P = 0.0313, respectively). The threshold for sNCT was unchanged in both groups of children, but the symptom score after sNCT was unchanged in the placebo group and significantly decreased in the active group (P = 0.0084). The nasal tryptase after sNCT was unchanged in the active group and significantly increased in the placebo group (P = 0.0218). Intergroup comparison showed a significant difference in oral tryptase and nasal tryptase after sNCT in favour of the active group. CONCLUSIONS: These interim results after only 1 year of treatment show that SLIT in children monosensitized to HDMs is able to avoid the spontaneous increase in both nasal sIgE antibodies and in local allergic inflammation in basal conditions. These outcomes are confirmed and supported by the decrease of symptoms in the active group combined with the increase of nasal tryptase only in the control group in both cases after sNCT.     

Cytogenetic and array CGH characterization of an intrachromosomal complex rearrangement of 4q in a patient with a 4q-phenotype

We report on a 3-year-old child who presented a de novo rearrangement of chromosome 4, detected on GTG banding and characterized by array CGH and FISH, as a complex intrachromosomal rearrangement with three deletions: del(q32.1q32.2), del(q33q34.1), del(q35.2), one tandem duplication dup(q34.3q35.1) and short normal regions in between. The study of karyotype-phenotype correlations in this and other patients with deletions of 4q suggests 4q33q34.1 as a candidate region for 4q-syndrome and for craniofacial development.     

Increased killer cell activity in insulin dependent (Type 1) diabetes mellitus

Summary Antibody dependent cell mediated cytotoxicity in relation to the levels of circulating killer cells was investigated in 16 newly diagnosed classical insulin dependent (Type 1) diabetics, 11 islet cell antibody positive non diabetic children with at least one HLA haplotype in common with their diabetic sibling, and in 15 normal controls. Antibody dependent cell mediated cytotoxicity was evaluated using, as target, ⁵¹Cr labelled human 0⁺ erythrocytes sensitised with an anti-CD antiserum. Killer cells were measured by the low affinity E-rosetting cell technique. Increased killer cell levels (>normal mean + 2SD) were accompanied by a significant enhancement in antibody dependent cell mediated cytotoxicity both in newly diagnosed diabetics (p < 0.05) and in unaffected siblings (p < 0.01). These preliminary results indicate that raised antibody dependent cell mediated cytotoxicity is a feature of insulin dependent diabetes at diagnosis and suggest that active B cell damage might be occurring some time before the onset of clinical symptoms.     

Multiple loci on human chromosome 11 control tumorigenicity of BK virus transformed cells

BK virus (BKV) is a human papovavirus that readily transforms rodent cells, but not human cells, to a neoplastic phenotype, suggesting that tumor-suppressor functions expressed in human cells control BKV oncogenicity. Transfer of a normal human chromosome 11 to BKV-transformed mouse cells suppresses the malignant phenotype. In this report we map the regions of chromosome involved in tumor suppression. Transfer of chromosome 11 to the BKV-transformed hamster cell line HKBK produces monochromosomic hybrids retaining only portions of the transferred human chromosome. We have compared the tumorigenicity of the hybrids with the molecular mapping of chromosome 11 retained regions. This analysis indicated that 3 regions of human chromosome 11, 11p15.5, 11p13 and 11q13, cooperate in tumor suppression. However, 11q13 seems the most important, since all the HKBK/H11-induced tumors analysed had lost this region, whereas 11p15.5 and 11p13 were sometimes retained. The chromosomal regions identified in this study are deleted in several types of human tumors, suggesting that the BKV transformation system specifically detects tumor-suppressor genes on chromosome 11 that are involved in human oncogenesis. This model may be of use in isolating and cloning such genes. The results of this report raise the possibility that BKV may have a synergistic tumorigenic effect in human cells where tumor-suppressor genes controlling its oncogenk potential are inactivated. © 1994 Wiley-Liss, Inc.     

Advanced glycosylation end product quantification: differently produced polyclonal antisera do not share the recognition of epitopes of different nature

Advanced glycosylation end products (AGE) which are probably involved in the pathogenesis of diabetic complications, comprise a series of related chemical structures. Thus different antisera might recognize particular AGE epitopes rather than the complete range of epitopes. To test this hypothesis, two antisera were raised using different immunization techniques and different AGE-carrier proteins as immunogens. The antisera reactivity towards different AGE-proteins under various experimental conditions was compared. Both antisera recognized all AGE-proteins, although with different binding curves. Following pre-incubation with carboxymethyllysine-BSA (CML-BSA) (an oxidation-derived AGE) one antiserum partially retained its reactivity, suggesting recognition of non-oxidation-derived AGE. This result was confirmed both in the cross-reactivity and the preincubation experiments and when the reactivity of the antisera was tested against antigens incubated under oxidative and non-oxidative conditions. These results confirmed the hypothesis that differently produced antisera may not share the recognition of epitopes of different nature and suggest the necessity to adopt a standardized methodology for the production of antisera for an accurate and reproductible determination of the in vivo AGE concentration.