A collection of cDNAs enriched in upper cortical layers of the embryonic mouse brain

In an attempt to elucidate the molecular basis of neuronal migration and corticogenesis, we performed subtractive hybridization of mRNAs from the upper cortical layers (layer I and upper cortical plate) against mRNAs from the remaining cerebral cortex at E15-E16. We obtained a collection of subtracted cDNA clones and analyzed their 3' UTR sequences, 47% of which correspond to EST sequences, and may represent novel products. Among the cloned sequences, we identified gene products that have not been reported in brain or in the cerebral cortex before. We examined the expression pattern of 39 subtracted clones, which was enriched in the upper layers of the cerebral cortex at embryonic stages. The expression of most clones is developmentally regulated, and especially high in embryonic and early postnatal stages. Four of the unknown clones were studied in more detail and identified as a new member of the tetraspanin superfamily, a putative RNA binding protein, a specific product of the adult dentate gyrus and a protein containing a beta-catenin repeat. We thus cloned a collection of subtracted cDNAs coding for protein products that may be involved in the development of the cerebral cortex.     

High femoral bone mineral content and density in male football (soccer) players

PURPOSE: This investigation examined the effect that long-term football (soccer) participation may have on areal bone mineral density (BMD) and bone mineral content (BMC) in male football players. METHODS: Dual energy x-ray absorptiometry (DXA) scans were obtained in 33 recreational male football players active in football for the last 12 yr and 19 nonactive subjects from the same population. Both groups had comparable age (23 +/- 4 yr vs 24 +/- 3 yr), body mass (73 +/- 7 kg vs 72 +/- 11 kg), height (176 +/- 5 cm vs 176 +/- 8 cm), and calcium intake (23 +/- 10 mg.kg(-1).d(-1) vs 20 +/- 11 mg.kg(-1).d(-1) (mean +/- SD). RESULTS: The football players showed 8% greater total lean mass (P < 0.001), 13% greater whole-body BMC (P < 0.001), and 5 units lower percentage body fat (P < 0.001) than control subjects. Lumbar spine (L2-L4) BMC and BMD were 13% and 10% higher, respectively, in the football players than in the control subjects (P < 0.05). Furthermore, football players displayed higher femoral neck BMC (24%, 18%, 23%, and 24% for the femoral neck, intertrochanteric, greater trochanter, and Ward's triangle subregions, respectively, P < 0.05) and BMD (21%, 19%, 21%, and 27%, respectively, P < 0.05) than controls. BMC in the whole leg was 16-17% greater in the football players, mainly because of enhanced BMD (9-10%) but also because of bone hypertrophy, since the area occupied by the osseous pixels was 7% higher (867 +/- 63 cm2 vs 814 +/- 26 cm2, P < 0.05). Leg muscle mass was 11% higher in the football players than in the control subjects (20,635 +/- 2,073 g vs 18,331 +/- 2,301 g, P < 0.001). No differences were found between the legs in either groups for BMC, BMD, and muscle mass. Left leg muscle mass was correlated with femoral neck BMC and BMD (P < 0.001), as well as with lumbar spine (L2-L4) BMC and BMD (P < 0.001). CONCLUSION: Long-term football participation, starting at prepubertal age, is associated with markedly increased BMC and BMD at the femoral neck and lumbar spine regions.     

Differential modulation of the immune response by breast- or formula-feeding of infants

Spontaneous integrin expression on CD4+, CD8+ and CD19+ lymphocytes at 6 months was significantly lower in breastfed than formula-fed infants ( p < 0.05). In another study of 59 formula-fed and 64 breastfed 12-month-old children blast transformation and cytokine production by lymphocytes, and T cell changes were measured before and after measles-mumps-rubella vaccination (MMR). Before vaccination, lymphocytes of breastfed children had lower levels of blast transformation without antigen ( p < 0.001), with tetanus toxoid ( p < 0.02) or Candida ( p < 0.04), and lower interferon-γ production ( p < 0.03). Fourteen days after the live viral vaccination, only the breastfed children had increased production of interferon-γ ( p < 0.02) and increased percentages of CD56+ ( p < 0.022) and CD8+ cells ( p < 0.004). These findings are consistent with a Thl type response by breastfed children, not evident in formula-fed children. Feeding mode has an important long-term immunomodulating effect on infants beyond weaning.     

Social skills training for primary school children: A 1-year follow-up study

Objective: To evaluate the effectiveness of the Rochester Social Problem Solving Program to reduce emotional and behavioural problems amongst primary school children.
Methodology: Children in years 3 and 4 at primary school were assessed prior to receiving the program, immediately after the program and 1 year after the program. At each assessment, the functioning of the children who received the program was compared to the functioning of children enrolled in years 3 and 4 at a comparable school who did not receive the program.
Results: The program improved the ability of children to cope with potentially difficult social situations. However, the program did not reduce the prevalence of teacher-reported or mother-reported childhood emotional and behavioural problems.
Conclusions: School-based social skills programs may be more effective in reducing childhood emotional and behavioural problems if they include components which focus specifically on childhood behaviour problems as well as components focusing on social skills and peer relationships.     

Incidence, population, and survival of cystic fibrosis in the UK, 1968-95. UK Cystic Fibrosis Survey Management Committee

The UK Cystic Fibrosis Survey holds data on all people resident in the UK who were diagnosed as having cystic fibrosis and born either since 1968 or before 1968 and alive in 1977. Thus, incidence may be reported from 1968 and prevalence from 1977. The previous estimates are updated to the end of 1995 from data held in the database on 23 August 1996. The incidence is now calculated as one in 2415 live births. The 1992 mid-year population was 6500 people with 65% aged under 16 years. Births outnumber deaths by 160 per year, which suggests a population of 7750 by the year 2000, with all the increase being in the adult age range. The survival of successive cohorts continues to be better than earlier cohorts, the linear descent of the curves is still evident. The infant mortality rate for cystic fibrosis is now under 20 per thousand per year and early childhood mortality is under five per thousand per year. The crude mortality rate for 1995 was 21 per thousand per year, but the standardised mortality ratio was about 3300.     

The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria): case reports of 23 new patients

OBJECTIVES: To further define the clinical spectrum of the disease for pediatric and metabolic specialists, and to suggest that the general pediatrician and pediatric neurologist consider succinic semialdehyde dehydrogenase (SSADH) deficiency in the differential diagnosis of patients with (idiopathic) mental retardation and emphasize the need for accurate, quantitative organic acid analysis in such patients. PATIENTS: The clinical features of 23 patients (20 families) with SSADH deficiency (4-hydroxybutyric acid-uria) are presented. The age at diagnosis ranged from 3 months to 25 years in the 11 male and 12 female patients; consanguinity was noted in 39% of families. OUTCOME MEASUREMENTS: The following abnormalities were observed (frequency in 23 patients): motor delay, including fine-motor skills, 78%; language delay, 78%; hypotonia, 74%; mental delay, 74%; seizures, 48%; decreased or absent reflexes, 39%; ataxia, 30%; behavioral problems, 30%; hyperkinesis, 30%; neonatal problems, 26%; and electroencephalographic abnormalities, 26%. Associated findings included psychoses, cranial magnetic resonance or computed tomographic abnormalities, and ocular problems in 22% or less of patients. Therapy with vigabatrin proved beneficial to varying degrees in 35% of the patients. Normal early development was noted in 30% of patients. CONCLUSIONS: Our data imply that two groups of patients with SSADH deficiency exist, differentiated by the course of early development. Our recommendation would be that accurate, quantitative organic acid analysis in an appropriate specialist laboratory be requested for any patients presenting with two or more features of mental, motor, or language delay and hypotonia of unknown cause. Such analyses are the only definitive way to diagnose SSADH deficiency; the diagnosis can be confirmed by determination of enzyme activity in white cells from whole blood. We think that increased use of organic acid determination will lead to increased diagnosis of SSADH deficiency and a more accurate representation of disease frequency. As additional patients are identified, we should have a better understanding of both the metabolic and clinical profiles of SSADH deficiency.     

Computed tomography in chronic inflammatory bowel disease

In children with complicated inflammatory bowel disease, conventional ultrasound imaging may not define the extent of extraluminal disease and the involvement of other viscera. Three children with chronic inflammatory bowel disease are presented, where computed tomography was well tolerated and provided valuable information on extraluminal disease, involvement of other organs, and the state of the bowel wall and mesentery. In children in whom ultrasound examination is inconclusive or limited by gas or tenderness, computed tomography can provide important information that may determine clinical management.     

Confidential inquiry into families with two siblings with cystic fibrosis

OBJECTIVE: To audit the care that had been provided to couples before the birth of a child with cystic fibrosis where a sibling had been previously diagnosed. DESIGN: Retrospective review of case notes. SAMPLE: Families where at least one affected child had been born between 1 January 1991 and 30 June 1995 and the diagnosis in the first child was made before the second affected pregnancy reached 20 weeks. The combination of information on these families with data from the prenatal diagnosis register allowed the reconstruction of a cohort of pregnancies in women with a previous affected child. MAIN RESULTS: Forty six eligible families with a second affected child were identified. Details from the paediatrician who had diagnosed the first affected child were obtained in 43 cases: all 43 couples were offered genetic counselling, but where provided by a paediatrician this was difficult to assess as no couple was sent a summary letter. Details were obtained from the obstetrician in the subsequent affected pregnancy in 42 cases: prenatal diagnosis was not offered in 10 (24%), offered and declined in 24 (57%), offered and accepted but termination declined in eight (19%). In the overall cohort of at risk pregnancies, the estimated rate of prenatal diagnosis offer was 97%, prenatal diagnosis uptake 86%, false negative prenatal diagnosis rate 0%, and uptake of termination 95%. CONCLUSIONS: (1) Parental choice was an important determinant of second affected births. (2) Despite widespread availability, prenatal diagnosis was not offered in an estimated 3% of at risk pregnancies. (3) There were shortcomings in counselling documentation, in particular failure to send a summary letter to counselled couples.