Trade-offs between acquired and innate immune defenses in humans

Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology.     

Increasing Perceptions of Self-Worth in Preadolescents Diagnosed with ADHD

Purpose: To test the effectiveness of a school-based, nurse-facilitated support group in increasing perceptions of scholastic competence, social acceptance, behavioral conduct, perceived athletic competence, perceived physical appearance, and perceived global self-worth in preadolescents diagnosed with attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD).
Design: A quasi-experimental design with 65 preadolescents diagnosed with ADD or ADHD in an upper-middle class community in the United States.
Methods: Participants randomly assigned to either the control or experimental group completed Harter's Self-Perception Profile for Children instrument at the beginning of the study and 4 weeks later. Students in the experimental condition participated in a school-nurse facilitated support group which met twice weekly for 4 weeks.
Findings: Participants in the support group had increased scores on each of the six subscales, with significant increases on four of the subscales, including perceived social acceptance, perceived athletic competence, perceived physical appearance, and perceived global self-worth.
Conclusion: Participation in a school-based, nurse-led support group was positively associated with perception of self-worth in preadolescents diagnosed with ADD or ADHD.     

High Prevalence of Developmental Disabilities in Children Admitted to a General Pediatric Inpatient Unit

Objective: Evaluate a) the prevalence of developmental disabilities (DD) in children admitted to a general pediatrics inpatient unit, and b) the number of children admitted to the unit with previously undiagnosed developmental disability. Methods: Prevalence was evaluated through retrospective record review. Subjects: One hundred ninety children older than five months of age admitted to a general pediatric unit. Results: Of 190 children admitted, 155 (81.6%) had adequate developmental screening documented in the record. Forty-nine (25.7% of total, 31.6% of screened) had a developmental disability, 22 (12.1% of total, 14.8% of screened) had a previously unrecognized disability. Sample prevalence of DD was: cerebral palsy (6.8%), developmental delay or mental retardation (8.4%), language delay (4.6%), learning disability (8.2%), and hearing loss (1.5%). New diagnoses included: three children with probable mental retardation (MR), nine with learning disability (may include mild MR), seven with language delay, three with abnormal motor skills (fine and/or gross motor), one each of: neurofibromatosis type I, hearing loss, cerebral palsy, dysphagia. Some children had more than one new diagnosis. Conclusion: The prevalence of disabilities in a general pediatrics inpatient unit is much higher than the prevalence in the community. Because almost half of the disabilities were previously unrecognized, acute hospitalization is an excellent opportunity to conduct developmental screening.     

Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism.

BACKGROUND: The HOXA1 gene plays a major role in brainstem and cranial morphogenesis. The G allele of the HOXA1 A218G polymorphism has been previously found associated with autism. METHODS: We performed case-control and family-based association analyses, contrasting 127 autistic patients with 174 ethnically matched controls, and assessing for allelic transmission disequilibrium in 189 complete trios. RESULTS: A, and not G, alleles were associated with autism using both case-control (chi(2) = 8.96 and 5.71, 1 df, p <.005 and <.025 for genotypes and alleles, respectively), and family-based (transmission/disequilibrium test chi(2) = 8.80, 1 df, p <.005) association analyses. The head circumference of 31 patients carrying one or two copies of the G allele displayed significantly larger median values (95.0th vs. 82.5th percentile, p <.05) and dramatically reduced interindividual variability (p <.0001), compared with 166 patients carrying the A/A genotype. CONCLUSIONS: The HOXA1 A218G polymorphism explains approximately 5% of the variance in the head circumference of autistic patients and represents to our knowledge the first known gene variant providing sizable contributions to cranial morphology. The disease specificity of this finding is currently being investigated. Nonreplications in genetic linkage/association studies could partly stem from the dyshomogeneous distribution of an endophenotype morphologically defined by cranial circumference.     

Directional tuning of motion-sensitive cells in the anterior superior temporal polysensory area of the macaque

An investigation was made into the directional sensitivity of cells in the macaque anterior superior temporal polysensory region (STPa) to the motion of objects. The cells studied were sensitive to the presence of motion but showed little or no selectivity for the form of the stimulus. Directional tuning was not continuously distributed about all possible directions. The majority of cells were most responsive to motion in a direction within 15° of one of the three cartesian axes (up/down, left/right, towards/away). Tuning to direction varied in sharpness. For most (34/37) cells the angular change in direction required to reduce response to half maximal was between 45 and 70° (for 3/37 cells it was > 90°). The estimates of the directionality (median I _d = 0.97) of STPa cells was similar to that reported for posterior motion processing areas (the middle temporal area, MT, and the medial superior temporal area, MST). The tuning for direction (sharpness, distribution and discrimination) of the motion-sensitive STPa cells were found to be similar to the tuning for perspective view of STPa cells selective for static form of the head and body. On average the STPa responses showed a 100- to 300-ms transient burst of activity followed by a tonic discharge maintained at approximately 20% of the peak firing rate for the duration of stimulation. The responses of motion-sensitive STPa cells occurred at an earlier latency (mean 91 ms) than responses of cells selective for static form (mean 119 ms), but the time course of responses of the two classes of cell were similar in many other respects. The early response latency and directional selectivity indicate that motion sensitivity in STPa cells derives from the dorsal visual pathway via MT/MST. The similarity of tuning for direction and perspective view within STPa may facilitate the integration of motion and form processing within this high-level brain area.     

Pleiotropy in Coffin-Lowry syndrome: Sensorineural hearing deficit and premature tooth loss as early manifestations

We report on 7 patients (6 M, 1 F) with Coffin-Lowry syndrome who have a sensorineural hearing deficit in addition to developmental delay and characteristic facial changes. One of the patients also had a history of premature exfoliation of primary teeth. These are previously unappreciated clinical signs that may aid in the early diagnosis of Coffin-Lowry syndrome. Early diagnosis and recognition of a hearing deficit in the patient can lead to the use of hearing aids to help the patient achieve his or her full potential. These “;new”; clinical manifestations expand the phenotype of Coffin-Lowry syndrome and constitute an additional indication of pleiotropy. © 1993 Wiley-Liss, Inc.     

Normal intracortical excitability in developmental stuttering.

Persistent developmental stuttering (PDS) shares clinical features with task-specific dystonias. In these dystonias, intracortical inhibition is abnormally weak. We therefore sought to determine intracortical inhibition and intracortical facilitation in PDS. In 18 subjects with PDS since childhood (mean age, 39.4 [SD 13.0] years) and 18 speech-fluent controls (43.6 [14.3] years), we investigated resting and active motor thresholds as well as intracortical inhibition and facilitation of the optimal representation of the abductor digiti minimi of the dominant hand using transcranial magnetic stimulation. In PDS, the resting and active motor thresholds were increased, whereas intracortical inhibition and facilitation were normal. Normal intracortical excitability makes a pathophysiological analogy between focal dystonia and PDS less likely. The enhanced motor threshold suggests reduced motor cortical neuronal membrane excitability in PDS.     

Causality Between the Amplitude and Frequency of Cardiac Oscillations

Using an information-theoretic approach, causality between the systolic amplitude in blood pressure and the frequency of the heart beat was analyzed. Blood pressure and ECG were noninvasively recorded in young, healthy subjects. Three successive measurements were performed: during spontaneous breathing and during paced respiration—at frequencies both higher and lower than that of spontaneous respiration. We demonstrate that the amplitude and frequency of the cardiac rhythm are synchronized for most of the time. The synchronization is stronger during paced respiration at a frequency lower than that of spontaneous breathing. Episodes where the cardiac frequency was driven by the systolic pressure were also detected during slow, paced respiration.