Stratification based on language-related endophenotypes in autism: attempt to replicate reported linkage.

The identification of autism susceptibility genes has been hampered by phenotypic heterogeneity of autism, among other factors. However, the use of endophenotypes has shown preliminary success in reducing heterogeneity and identifying potential autism-related susceptibility regions. To further explore the utility of using language-related endophenotypes, we performed linkage analysis on multiplex autism families stratified according to delayed expressive speech and also assessed the extent to which parental phenotype information would aid in identifying regions of linkage. A whole genome scan using a multipoint non-parametric linkage approach was performed in 133 families, stratifying the sample by phrase speech delay and word delay (WD). None of the regions reached suggested genome-wide or replication significance thresholds. However, several loci on chromosomes 1, 2, 4, 6, 7, 8, 9, 10, 12, 15, and 19 yielded nominally higher linkage signals in the delayed groups. The results did not support reported linkage findings for loci on chromosomes 7 or 13 that were a result of stratification based on the language delay endophenotype. In addition, inclusion of information on parental history of language delay did not appreciably affect the linkage results. The nominal increase in NPL scores across several regions using language delay endophenotypes for stratification suggests that this strategy may be useful in attenuating heterogeneity. However, the inconsistencies in regions identified across studies highlight the importance of increasing sample sizes to provide adequate power to test replications in independent samples.     

Novel PCR-restriction fragment length polymorphism method for determining serotypes or serogroups of Streptococcus pneumoniae isolates

Serotyping Streptococcus pneumoniae is a technique generally confined to reference laboratories, as purchasing pneumococcal antisera is a huge investment. Many attempts have been made to modify serological agglutination techniques to make them more accessible, and more recently developments in serotyping have focused on molecular techniques. This paper describes a PCR assay which amplifies the entire capsulation locus between dexB and aliA. Amplicons are digested to produce serotype-specific patterns. We have shown, using 81 epidemiologically unrelated strains representing 46 different serotypes, that the patterns correlate with a 90 to 100% similarity range for the same serotype or serogroup. Prospective testing of 73 isolates of unknown serotype confirmed reliable serotype attribution, and serotype profiles are reproducible on repeated testing. Once our database contains all 90 serotypes, this technique should be fully portable, cost-effective, and useful in any laboratory with sufficient molecular experience.     

Isolated cardiac recurrence of acute lymphoblastic leukemia characterized by t(11;19) two years after unrelated allogeneic bone marrow transplantation

A 33-year-old male presented with acute lymphoblastic leukemia (ALL) characterized by translocation (11;19)(q23;p13.3). He received an allogeneic bone marrow transplant from a matched unrelated donor. Two years later his disease relapsed with an isolated intracardiac mass, presenting as right heart failure. He had no evidence of concomitant relapse in the bone marrow. Tumor cytogenetics revealed clonal evolution with the karyotype 46,XY,t(3;16)(q23;p13),t(11;19)(q23;p13.3), the chromosome 16 breakpoint involving the band where the genes for multidrug resistance-associated protein and CREB binding protein are known to reside. To our knowledge, this is the first report of an isolated extramedullary relapse of ALL in the heart.     

Acute and chronic ethanol does not affect incisional pain in neonatal rats

We have previously found that in post-natal day 7 rats withdrawal from acute and chronic ethanol (EtOH) exposure lowers mechanical thresholds during withdrawal and exacerbates spontaneous pain responses to an inflammatory injury 4 days post-withdrawal. These findings suggested alterations in somatosensory pathways following EtOH exposure during the third trimester developmental equivalent. In this study we wanted to determine whether EtOH exposure during the third trimester equivalent exacerbates mechanical allodynia and thermal hyperalgesia produced by an incisional model of post-operative pain at post-natal day 21. The extent and duration of mechanical allodynia and thermal hyperalgesia following incision was measured and found to be unaffected by prior EtOH exposure.     

Umbilical cord blood screening for cytomegalovirus DNA by quantitative PCR.

BACKGROUND: Cytomegalovirus (CMV) infection, which is the most common congenitally transmitted infection, affects approximately 1% of neonates worldwide. Despite its prevalence, no convenient screening test for neonatal CMV infection has been implemented. OBJECTIVE: The purpose of this pilot study was to evaluate the feasibility and yield of screening umbilical cord blood for CMV DNA emiaby quantitative PCR. STUDY DESIGN: Umbilical cord blood was tested for CMV DNAemia using a commercial quantitative PCR assay. Maternal CMV serostatus at the time of delivery was assessed by testing for CMV IgG and IgM antibodies in serum. CONCLUSIONS: Screening for congenital CMV infection with PCR is easily incorporated into routine labor and delivery care using discarded cord blood specimens to identify neonates whose infection is otherwise undiagnosed. Among 433 infants tested, two (0.5%) had DNAemia detected in cord blood, one of whom was symptomatic, and both of whose mothers were CMV IgG positive and IgM negative. Viremic neonates identified by screening with PCR may be at high risk of developing long-term neurological complications of CMV infection and cannot reliably be identified using clinical presentation or maternal serology. Because of its convenience, cord blood CMV screening with PCR should be further investigated for incorporation into neonatal screening protocols.     

Immunological studies in patients with juvenile-onset myasthenia gravis and in their relatives

Fifty-four patients who developed myasthenia before the age of 20 had an increased incidence of autoantibodies similar to that in adult-onset myasthenics, except that there was no significant increase of striated muscle antibodies. The increase in thyroid antibodies was associated with an increase of thyroid disease.

Their 150 relatives showed a significant increase in thyroid antibodies, in thyroid disease, and a non-significant increase in the five other autoantibodies studied. There was aggregation of thyroid antibodies in some families.

Two patients and one relative were deficient for immunoglobulins (one patient and one father for IgA and one patient for IgM).

These familial immunological abnormalities, which are more marked in the families of patients with juvenile-onset myasthenia than in the families of adult-onset patients, point to fundamental genetic immunopathogenesis of the disease.

     

Response properties of single neurons in the zebra finch auditory midbrain: response patterns, frequency coding, intensity coding, and spike latencies

The avian mesencephalicus lateralis, dorsalis (MLd) is the auditory midbrain nucleus in which multiple parallel inputs from lower brain stem converge and through which most auditory information passes to reach the forebrain. Auditory processing in the MLd has not been investigated in songbirds. We studied the tuning properties of single MLd neurons in adult male zebra finches. Pure tones were used to examine tonotopy, temporal response patterns, frequency coding, intensity coding, spike latencies, and duration tuning. Most neurons had no spontaneous activity. The tonotopy of MLd is like that of other birds and mammals; characteristic frequencies (CFs) increase in a dorsal to ventral direction. Four major response patterns were found: 1) onset (49% of cells); 2) primary-like (20%); 3) sustained (19%); and 4) primary-like with notch (12%). CFs ranged between 0.9 and 6.1 kHz, matching the zebra finch hearing range and the power spectrum of song. Tuning curves were generally V-shaped, but complex curves, with multiple peaks or noncontiguous excitatory regions, were observed in 22% of cells. Rate-level functions indicated that 51% of nononset cells showed monotonic relationships between spike rate and sound level. Other cells showed low saturation or nonmonotonic responses. Spike latencies ranged from 4 to 40 ms, measured at CF. Spike latencies generally decreased with increasing sound pressure level (SPL), although paradoxical latency shifts were observed in 16% of units. For onset cells, changes in SPL produced smaller latency changes than for cells showing other response types. Results suggest that auditory midbrain neurons may be particularly suited for processing temporally complex signals with a high degree of precision.     

BEAUTY and the breast: is adjuvant chemotherapy the right time for a beauty boost? Lessons learned from a large randomized controlled trial

Quality of Life Research - Beauty care (BTC) is offered at many cancer hospitals having a great uptake among patients. Nevertheless, its benefits in the Quality of life (QoL) of cancer survivors...