The effect of blood-lead on children's ability and attainment was investigated in a sample of 855 boys and girls aged 6-9 years from eighteen primary schools within a defined area of central ...Edinburgh. The geometric mean blood-lead value was 10.4 micrograms/dl. In a stratified subsample, 501 children completed individual tests of cognitive ability and educational attainment from the British Ability Scales (BAS). An extensive home interview with a parent was also done. Multiple regression analyses showed a significant negative relation between log blood-lead and BAS combined score, number skills, and word reading when thirty-three possible confounding variables were taken into account. There was a dose-response relation between blood-lead and test scores, with no evidence of a threshold. The size of the effect was small compared with that of other factors. Lead at low levels of exposure probably has a small harmful effect on the performance of children in ability and attainment tests.
Plasma gamma-aminobutyric acid (pGABA) is an index of brain GABA activity and a peripheral marker of mood disorder. Previous research has indicated that pGABA is abnormally low in approximately 40% ...of patients symptomatic with primary unipolar depression. We have now measured pGABA in a series of patients with bipolar disorder. Blood samples for GABA determinations were collected soon after admission to hospital or clinic while patients were symptomatic. In both manic and depressed phase bipolar patients, mean levels of pGABA were significantly lower than in healthy control subjects. The distribution of pGABA in bipolar patients, whether manic or depressed, was similar to that in symptomatic unipolar depression, with 30% to 40% having pGABA levels lower than the control range. These data indicate that low pGABA is not specific to the depressed state, as it is also found in the manic phase of bipolar disorder. Low pGABA may represent a shared biologic correlate between bipolar and unipolar illness.
Development of a new testing machine, which stabilizes the pelvis, allowed us to evaluate the lumbar extensor muscles before and after training. Fifteen healthy subjects (29.1 +/- 8 years of age) ...trained 1 day per week for 10 weeks and 10 healthy subjects (33.7 +/- 16 years of age) acted as controls. Training consisted of 6 to 15 repetitions of full range of motion variable resistance lumbar extension exercise to volitional fatigue and periodic maximal isometric contractions taken at seven angles through a full range of motion. Before and after the 10 week training period, subjects completed a maximum isometric strength test at seven angles through a 72 degrees range of motion (0 degrees, 12 degrees, 24 degrees, 36 degrees, 48 degrees, 60 degrees, and 72 degrees of lumbar flexion). The training group significantly improved in lumbar extension strength at all angles (P less than or equal to 0.01). The result at 0 degrees (full extension) showed an increase from 180.0 +/- 25 Nm to 364.1 +/- 43 Nm (+102%) and at 72 degrees (full flexion) from 427.4 +/- 44.1 to 607.4 +/- 68 (+42%) Nm. Results from the control group showed no change (P greater than or equal to 0.05). The magnitude of gain shown by the training group reflects the low initial trained state of the lumbar extensor muscles. These data indicate that when the lumbar area is isolated through pelvic stabilization, the isolated lumbar extensor muscles show an abnormally large potential for strength increase.
Allogeneic stem cell transplantation is a standard treatment for patients with high-risk relapsed leukemia, aplastic anemia, congenital bone marrow failure syndromes, and relapsed or recurrent ...lymphoid malignancies. Over 20,000 allogeneic transplants are conducted annually worldwide, confirming its effectiveness as a treatment for patients with otherwise lethal malignancies. Cure rates range from 15-80% depending on preexisting conditions and diagnoses. Patients receive high dose chemotherapy to eliminate malignant cells and allow engraftment of donor cells. However, this intense treatment regimen leaves patients vulnerable to infections, relapse, and acute graft-versus-host disease (aGvHD). aGvHD is a disease characterized by selective epithelial damage to target organs. Complications from aGvHD result in increased morbidity and mortality in transplant recipients. aGvHD is initiated by mature CD4 + and CD8+ T cells present in the stem cell inoculum. These donor T cells replenish host T cell immunity and promote engraftment. Conversely, damage to target tissue, predominantly the skin, liver, and gastrointestinal tract, in aGvHD is caused by immunologically functional donor T lymphocytes that respond to genetic disparities in host antigens. Our laboratory has focused on the migration of T cells in aGvHD pathogenesis. Coronins are a family of seven-actin binding proteins found in all eukaryotic organisms. Functional data in non-mammalian systems have shown a role for Coronins in cell migration, motility, and cytokinesis. The most well studied of the proteins, Coronin 1A (Coro 1A) is expressed primarily in hematopoietic cells and the focus of our studies. Here, we demonstrate a requirement for Coro 1A in the pathogenesis of acute GvHD. Delayed entry and impaired egress from secondary lymphoid tissues were observed in T cells deficient in Coro 1A. Decreased expression of the C-C chemokine receptor type 7 (CCR7) and the signaling lipid receptor, sphingosine 1 phosphate receptor 1 (S1Pr1) were detected in Coro 1A deficient T cells. Egress to target aGvHD was limited by Coro 1A deficient cells due to accumulation in gastrointestinal lymph nodes. These data suggest that therapeutic approaches that prevent entry and egress from secondary lymphoid organs may effective treatment options for acute GvHD.
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