Testicular cancer susceptibility in the 129.MOLF-Chr19 mouse strain: additive effects,gene interactions and epigenetic modifications

Testicular germ cell tumors (TGCTs) are the most common solid cancers affecting young men. Although the evidence for genetic predisposition to TGCTs in humans is compelling, the genetic control of susceptibility is poorly understood. The 129S1/SvImJ (129/Sv) inbred strain of mice is an excellent model for studying TGCT susceptibility. We previously reported a new mouse strain, the 129.MOLF-Chr19 chromosome substitution strain, which develops spontaneous TGCTs at a high frequency (70-80%) as compared with the much lower rate in the 129/Sv strain (5%). To characterize the genetic control of TGCT susceptibility, we created a panel of single- and double-congenic strains derived from 129.MOLF-Chr19. The frequency of TGCTs in these strains suggests that several genes with additive and epistatic effects located at distinct sites on chromosome 19 control susceptibility. However, an alternative interpretation involving epigenesis is based on a striking correlation between TGCT frequency and the length of the MOLF-derived congenic segment, regardless of their chromosomal location on Chr 19 in each congenic strain. We also show that bilateral TGCT cases result from the coincidental co-occurrence of unilateral TGCTs rather than from the action of distinct genes that control susceptibility to bilateral versus unilateral TGCT cases. Finally, we propose that these TGCTs result from disrupted testicular and spermatogenic developmental programs.     

Impact of Hepatitis B and Hepatitis C Virus Infections in a Hematology-Oncology Unit at a Children's Hospital in Nicaragua, 1997 to 1999

The risk of acquiring both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in patients with hematological-oncological disorders has been documented. However, the impact and risk factors for such infections from different geographical areas vary, and the use of both immunological and molecular assays to determine HCV infections has been our approach. Children from a hematology-oncology unit (HOU) in Nicaragua were studied for both HBV and HCV serological markers; studies for the latter used both immunological (anti-HCV) and molecular (HCV RNA) assays. The children from the HOU included patients with leukemia, lymphoma, other neoplasias, and anemia and a smaller group with other hematological diseases. As a control group, children from other units at the same hospital were enrolled, as well as health care workers attending both patient populations. Pertinent clinical and personal data for each child at the HOU were obtained for statistical analysis. Of the 625 children from the HOU enrolled in this study 53.3% were infected with HCV and 29.4% had a prior or present HBV infection. In the child patient control group 3.2% had HBV markers and all were negative for HCV. The group of children with leukemia had the highest infection rate for both HBV and HCV. However, the determination of anti-HCV was found to have an overall low sensitivity in children from HOU, and a retest consisting of a molecular assay to determine HCV RNA was performed to better establish the total number of HCV-infected subjects in this group. The highest independent risk factor for infection was hospitalization. The very high prevalence rates for both HBV and HCV infection in this patient group indicate an urgent need to implement better control of known risk factors and to consider the use of both immunological and molecular assays for HCV diagnostic purposes.     

Weight Status and BMI-Related Traits in Adolescent Friendship Groups and Role of Sociodemographic Factors: The European IDEFICS/I. Family Cohort

BackgroundDuring adolescence, health behaviors and weight status are increasingly influenced by friendship and peer networks. This paper examines resemblances in weight-related characteristics and how they differ by sociodemographic factors.MethodsOver 3,000 friendships were reported by 1,603 adolescents, aged 11–16 years, who participated in the school-based I. Family study in 6 European countries. Each “source child” named 1–10 friends for whom standardized weight-related traits were available in the same survey. The mean value of the friends'' traits weighted by time spent together was calculated, and related to the source child''s trait. Country, age and sex of the source child, parental education, and immigrant background were considered for confounding and moderation.ResultsSource children''s z-scores of body fat percent and BMI were positively associated with their friends'' characteristics, in particular if they had highly educated parents. Positive associations were also found regarding the frequency of fast-food consumption, impulsivity, screen time, preference for sugar-sweetened foods, and hours spent in sports clubs, in increasing order of effect size. Additionally, correlations were observed between friends'' cognitive and school functioning and being bullied. No associations were seen for a preference for high-fat foods, weight concerns, and health-related quality of life. Finally, parental education and immigrant background were associated between friends in all countries except Sweden, where no associations were observed.ConclusionAdolescent friends shared a number of weight-related characteristics. For weight measures per se, positive associations with friends'' characteristics were only observed in adolescents with high parental education. Associations regarding energy-balance behaviors and indicators of school-related well-being did not differ by parental education. Parental education and immigrant background correlated positively in friends in most countries showing that social aggregation is already occurring in adolescence. The wide spectrum of friendship associations in weight-related traits and behaviors suggests that health promotion initiatives in adolescents should be directed towards peer groups in both school-related and leisure-time environments.ISRCTN RegistryPan-European IDEFICS/I. Family children cohort (ID ISRCTN62310987; https://doi.org/10.1186/ISRCTN62310987).     

SSCP analysis of paraffin wax embedded tissues in a family with an atypical form of Fabry disease

To investigate the distribution of a single base pair mutation within a family with one known case of Fabry disease, DNA from paraffin wax embedded necropsy material was studied using single-strand conformation polymorphism (SSCP) analysis. The proband, who presented with an atypical form of Fabry disease, had a G to A transition in exon 6 of the α-galactosidase A gene. This patient had mainly cardiac symptoms and late onset disease. Further cases of coronary disorders occurred in this family, including the proband's brother who died at 42 years of age of a cardiac disorder. Formalin fixed, paraffin wax embedded material from the brother and two more distant relatives was available for analysis. SSCP analysis showed that the proband's brother also carried the G to A transition. Thus, the atypical form of Fabry disease and unrelated cardiac diseases with similar clinical symptoms occurred within a single family. The variant form is rare but may account for a few of the numerous cases of cardiac disease in men and should be considered when clusters of cases of cardiac disease occur within a single family.     

Anxiolytic effects of intra-amygdaloid injection of the D1 antagonist SCH23390 in the rat

The intercalated islands are intra-amigdaloid clusters of D1 receptor rich GABAergic neurons, which control impulse traffic between the basolateral complex and the central nucleus of the amygdala. As dopaminergic transmission within the amygdala may play a role in anxiety, the effect of the D1 antagonist SCH23390 microinjected mainly close to the rostral intercalated islands in rats was studied, using the White and Black Box test. SCH23390 reduced anxiety by an increase in the latency of the first entry into the black compartment and by an increase in the total time spent in the white compartment of the White and Black Box test, while there was no significant modification of locomotion. It is suggested that blockade of D1 receptors in the rostral intercalated islands may reduce anxiety through a reduction of GABA-mediated dishinibition of the central amygdaloid nucleus.     

The Diversity of Antigen-Specific TCR Repertoires Reflects the Relative Complexity of Epitopes Recognized

Antigen-selected T cell receptor (TCR) repertoires vary in complexity from very limited to extremely diverse. We have previously characterized two different CD8 T cell responses, which are restricted by the same mouse major histocompatibility complex (MHC) class I molecule, H-2 K^d. The TCR repertoire in the response against a determinant from Plasmodium berghei circumsporozoite protein (PbCS; region 252–260) is very diverse, whereas TCRs expressed by clones specific for a determinant in region 170–179 of HLA-CW3 (human) MHC class I molecule show relatively limited structural diversity. We had already demonstrated that cytolytic T lymphocyte (CTL) clones specific for the PbCS peptide display diverse patterns of antigen recognition when tested with a series of single Ala-substituted PbCS peptides or mutant H-2 K^d molecules. We now show that CW3-specific CTL clones display much less diverse patterns of recognition. Our earlier functional studies with synthetic peptide variants suggested that the optimal peptides recognized were 9 (or 8) residues long for PbCS and 10 residues long for CW3. We now present more direct evidence that the natural CW3 ligand is indeed a 10-mer. Our functional data together with molecular modeling suggest that the limited TCR repertoire selected during the CW3 response is not due to a paucity of available epitopes displayed at the surface of the CW3 peptide/K^d complex. We discuss other factors, such as the expression of similar self MHC peptide sequences, that might be involved in trimming this TCR repertoire.     

Pulmonary tuberculosis due to bacille Calmette-Guérin

Summary Immunotherapy using bacille Calmette-Guérin (BCG) has gained increasing acceptance in the management of superficial bladder cancer. Systemic reactions after intravesical instillation of BCG are rare. However, when the therapy is complicated, the lung often becomes involved. Since the pathogenesis of lung infiltrates after immunotherapy is unknown, we report on a patient who developed a lung infiltrate after receiving BCG immunotherapy for bladder cancer. The infectious etiology was established by culture confirmation of a BCG strain in the broncheoalveolar lavage fluid.Abbreviation BCG bacille Calmette-Guérin