Oculoauriculovertebral anomaly: Segregation analysis

Seventy-four families of probands with oculoauriculovertebral anomaly were evaluated, including 116 parents and 195 off-spring. Relatives were examined to identify ear malformations, mandibular anomalies, and other craniofacial abnormalities. For segregation analysis using POINTER, selection of the sample was consistent with single as-certainment. Different population liabilities were used for probands and relatives, because affection was narrowly defined for probands and broadly defined for relatives. The hypothesis of no genetic transmission was rejected. The evidence favored autosomal dominant inheritance; recessive and polygenic models were not distinguishable. © 1992 Wiley-Liss, Inc.     

Formation of rabbit reaginic antibodies to protein and hapten—protein conjugates

The capacities of BSA and DNP—protein conjugates to evoke reagin formation in rabbits were compared. Reagins to DNP generally appeared earlier and disappeared more rapidly from the circulation than did anti-BSA reagins. Initial formation of reagins proceeded with a logarithmic phase indicating a doubling time of 7–8 hours. Booster antigen injections resulted in some cases in a reagin response after a shorter latent phase than that observed after primary immunization. A secondary reagin response was more readily evoked in rabbits with low titres of agglutinating antibodies than in those with high titres. Anti-DNP reagins were demonstrable in a higher percentage of the injected rabbits than were anti-BSA reagins. The two types of reagins were equally sensitive to heat and 2-mercaptoethanol. A positive correlation between serum levels of anti-DNP but not anti-BSA reagins and agglutinating antibodies was demonstrated. Some evidence that a low antigen dose was more efficient than a high dose in evoking reagin formation was obtained. Treatment of rabbits with 6-mercaptopurine during the 1st week following antigen injection resulted in an increased latent phase and an enhancement of the production of anti-BSA reagins and some suppression of the formation of anti-DNP reagins.     

Kinesiophobia and symptomatology in chronic fatigue syndrome: A psychometric study of two questionnaires

Objectives. The aims of the study were to examine the reliability of the Dutch and French versions of the Tampa scale kinesiophobia (TSK) version chronic fatigue syndrome (CFS), and to examine the reliability and validity of the Dutch and French versions of the CFS symptom list. Design. Repeated‐measures design. Methods. Native Dutch speakers (N=100) and native French (N=48) speakers fulfilling the diagnostic criteria for CFS were asked to list the five most important symptoms and to complete the TSK–CFS, the CFS symptom list, and the Short Form 36 Health Status Survey or SF‐36. A modified version of the TSK–CFS and the CFS symptom list was filled in within 24 hours of the first assessment. Results. The French and Dutch version of the TSK–CFS and CFS symptom lists displayed good reliability (ICC≥.83). The CFS symptom list was internally consistent (Cronbach's α≥.93) and concurrently valid with the SF‐36. For the native Dutch and French speakers, respectively, 82 and 78% of the self‐reported symptoms matched the content of CFS symptom list. Conclusions. The results are in support of the psychometric properties of the French and Dutch versions of both the TSK–CFS and the CFS symptom list for assessing kinesiophobia and symptom severity, respectively.     

Peanut-induced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry

Background

Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%–1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents.

Methods

Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre.

Results

3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004).

Conclusions

The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition.

     

Lymphocyte Transformation in Syphilis: an In Vitro Correlate of Immune Suppression In Vivo?

Suppression of cellular immunity during primary and secondary infection may explain, in part, the unusual clinical evolution of syphilis. We have previously shown that lymphocytes from normal subjects undergo blastic transformation when exposed in vitro to Treponema refringens. This response was suppressed in patients with syphilis. the suppression being unrelated to serum factors. In the present paper we studied lymphocyte response in vitro to T. refringens, T. reiter, and T. pallidum as well as to monilia and trychophytins. The response to these antigens was suppressed in patients with syphilis although the response to phytohemagglutinin. pokeweed mitogen, and streptolysin was normal. These data support the hypothesis that human infection with T. pallidum is followed by a complex interaction between cellular and humoral immunity, the former being suppressed in primary and secondary stages.     

Localizing a putative mutation as the major contributor to the development of sporadic Hirschsprung disease to the RET genomic sequence between the promoter region and exon 2

Hirschsprung disease (HSCR), a congenital disorder characterized by intestinal obstruction due to absence of enteric ganglia along variable lengths of the intestinal tract, occurs both in familial and sporadic cases. RET mutations have been found in approximately 50% of the families, but explains only a minority of sporadic cases. This study aims at investigating a possible role of RET in sporadic HSCR patients. Haplotypes of 13 DNA markers, within and flanking RET, have been determined for 117 sporadic HSCR patients and their parents. Strong association was observed for six markers in the 5' region of RET. The largest distortions in allele transmission were found at the same markers. One single haplotype composed of these six markers was present in 55.6% of patients versus 16.2% of controls. Odds ratios (ORs) revealed a highly increased risk of homozygotes for this haplotype to develop HSCR (OR>20). These results allowed us to conclude that RET plays a crucial role in HSCR even when no RET mutations are found. An unknown functional disease variant(s) with a dosage-dependent effect in HSCR is likely located between the promoter region and exon 2 of RET.     

Cytogenetic analysis of 100 consecutive newly diagnosed cases of acute lymphoblastic leukemia in Rio de Janeiro

We report the cytogenetic analysis of newly diagnosed Brazilian children with acute lymphocytic leukemia (ALL). We investigated 100 ALL cases from four different institutions in Rio de Janeiro. The frequency of chromosomal abnormalities was 92.3%. The karyotype profile and recurrent abnormalities found in this study do not differ essentially from those described by other groups. Although the Brazilian population is usually the product of different ethnic groups, our results show that the frequency of each recurrent abnormality is similar to that found in populations without our degree of diverse ethnic composition. Hence, our results suggest that childhood ALL in Brazil has the same biological features as that in developed countries, supporting the use of similar treatment protocols. We can therefore expect to reach the same survival rates in the coming years, depending possibly on the efficacy of the support therapy and extent of social assistance.     

Comparison of DNA- and RNA-based methods for detection of truncating BRCA1 mutations

A number of methods are used for mutational analysis of BRCA1, a large multi-exon gene. A comparison was made of five methods to detect mutations generating premature stop codons that are predicted to result in synthesis of a truncated protein in BRCA1. These included four DNA-based methods: two-dimensional gene scanning (TDGS), denaturing high performance liquid chromatography (DHPLC), enzymatic mutation detection (EMD), and single strand conformation polymorphism analysis (SSCP) and an RNA/DNA-based protein truncation test (PTT) with and without complementary 5' sequencing. DNA and RNA samples isolated from 21 coded lymphoblastoid cell line samples were tested. These specimens had previously been analyzed by direct automated DNA sequencing, considered to be the optimum method for mutation detection. The set of 21 cell lines included 14 samples with 13 unique frameshift or nonsense mutations, three samples with two unique splice site mutations, and four samples without deleterious mutations. The present study focused on the detection of protein-truncating mutations, those that have been reported most often to be disease-causing alterations that segregate with cancer in families. PTT with complementary 5' sequencing correctly identified all 15 deleterious mutations. Not surprisingly, the DNA-based techniques did not detect a deletion of exon 22. EMD and DHPLC identified all of the mutations with the exception of the exon 22 deletion. Two mutations were initially missed by TDGS, but could be detected after slight changes in the test design, and five truncating mutations were missed by SSCP. It will continue to be important to use complementary methods for mutational analysis.     

Distribution of cytoskeletal structures and organelles of the host cell during evolution of the intracellular parasitism by Trypanosoma cruzi

The distribution of microtubules, microfilaments, mitochondria, Golgi complex and endosomes/lysosomes was analyzed in Vero cells allowed to interact for different periods of time with the pathogenic protozoan Trypanosoma cruzi and observed by confocal laser scanning microscopy. Microtubules were revealed using a mouse monoclonal anti-alpha-tubulin antibody. Actin filaments were revealed using phalloidin-rhodamine. To identify mitochondria, endosomes/lysosomes and the Golgi complex the cells were labelled with Rhodamine 123, Lucifer yellow and C6-NBD-ceramide, respectively. During cell invasion actin filaments concentrate at the site of parasite penetration in some, but not in all cells, probably depending upon the mechanism used by the trypomastigote form to penetrate into the host cells. Following internalization the trypomastigote form gradually changes into the amastigote form, disruption of the parasitophorous vacuole membrane takes place and the amastigote form enters in direct contact with host cell structures and organelles, and starts to divide. The presence of the parasite in the cytoplasm of the host cell did not induce significant changes in the distribution of actin filaments, microtubules, the Golgi complex, mitochondria and endosomes/lysosomes during the first 48 h of infection. Amastigote forms were seen close to the microtubules. After 72 h of interaction, the number of microtubules and microfilaments around the parasites was reduced and lysosomes and mitochondria were seen in between the parasites.