Who shall be served? Issues in screening for emotional and behavioral problems in school

Journal of Prevention - The major issues involved in the design and implementation of effective school screening programs are addressed, using data from a longitudinal study following over 500...     

Understanding the pathologic Haglund's deformity

Pathologic conditions behind the calcaneus are common, and may initiate during early childhood. The authors discuss osseous and soft tissue conditions involving the posterior-superior surface of the heel. Radiographic and clinical evaluation is considered. Treatment alternatives are also reviewed.     

CO2 laser techniques in destruction of verrucae plantaris: discussion of the blister technique, a more complete method of wart ablation

The popular "Cross-hatch" method of CO2 laser surgery is compared with the "blister" technique of verrucae destruction. The blister technique provides greater reliability of wart tissue destruction through better visualization of normal skin lines and verrucoid tissue. The procedure can be performed quickly and easily, and is less painful to the patient than other conventional methods of wart destruction.     

Contrasting effects of cyclophosphamide and prednisolone on the phenotype of human peripheral blood leukocytes

The cell surface phenotype of human peripheral blood mononuclear cells has been characterized before and after intravenous injection of cyclophosphamide or prednisolone. Low doses of cyclophosphamide (100-600 mg/m2) temporarily decrease levels of circulating B lymphocytes. Slightly higher doses of cyclophosphamide (200-600 mg/m2) produce transient depression of T8-, M1-, and Ia-positive cells. After doses of 200-400 mg cyclophosphamide/m2, T4-positive cells are spared, resulting in a transient elevation of the T4/T8 ratio. With higher doses of cyclophosphamide (greater than or equal to 600 mg/m2), all T cells are affected and the T4/T8 ratio declines to pretreatment levels. By contrast, intravenous injection of prednisolone at 40 mg/m2 reduces the T4/T8 ratio. Levels of both T4 and T8 cells decline, but T4 cells are affected more markedly than T8 cells.     

Loss of suppressor T cells in active multiple sclerosis. Analysis with monoclonal antibodies

To determine whether abnormalities of immunoregulatory T cells are associated with multiple sclerosis (MS), we characterized peripheral lymphocytes in 33 patients with untreated MS and compared them with 42 normal persons and 29 age-matched control subjects who had other neurologic diseases. For this analysis, we used monoclonal antibodies to the surface antigens of helper (T4) and suppressor (T5) T-cell subsets and to a common T-cell antigen (T3). In contract to normal persons and the controls with other neurologic diseases, the patients with MS had a reduced percentage of T3-positive (T3+) cells (P less than 0.05). More importantly, there was a selective decrease in T5-positive (T5+) cells in 11 of 15 patients with active MS, but in only one of 18 patients with inactive MS and in none of the normal persons or controls with neurologic disease (P less than 0.00001). Serial analysis of five patients with MS showed a correlation between the absence of the T5+ subset and disease activity. Thus, there is loss of peripheral suppressor cells in many patients with active MS, suggesting that immunoregulatory abnormalities contribute to the pathogenesis of the disease.     

Comparison of HIV Type 1 ADA gp120 monomers versus gp140 trimers as immunogens for the induction of neutralizing antibodies

Designing an immunogen for effective neutralizing antibody induction against diverse primary isolates of human immunodeficiency virus type 1 (HIV-1) is a high priority for HIV-1 vaccine development. Soluble gp120 envelope (Env) glycoprotein subunit vaccines elicit high titers of antibodies that neutralize T cell line-adapted (TCLA) strains but the antibodies possess poor neutralizing activity against many primary isolates. Previously, we generated soluble trimeric recombinant gp140 from the HIV-1 primary isolate ADA. Here we compared monomeric ADAgp120 and trimeric ADAgp140 as immunogens for neutralizing antibody responses in guinea pigs. Both immunogens generated a neutralizing antibody response that was detectable against the vaccine strain and several heterologous strains. The magnitude of this response was significantly greater in ADAgp140-immunized animals when measured against the TCLA strain, MN, and the R5 primary isolate, Bal. Two additional isolates (SS1196 and Bx08) were neutralized equally by sera from both groups of animals whereas other isolates were neutralized weakly or not at all. Despite equal titers of V3 loop specific binding antibodies in sera from both groups of animals, neutralization of ADA by sera from gp140-immunized animals was insensitive to the presence of ADA-V3 peptide, whereas addition of this peptide to sera from gp120- immunized animals blocked all detectable neutralizing activity against ADA. These results support the idea that trimeric gp140 is an improved immunogen compared to monomeric gp120 but that additional improvements are required to afford broad protection against a spectrum of heterologous primary HIV-1 isolates. This ADAgp140 immunogen may be considered a starting point from which to engineer additional improvements for cross-reactive neutralizing antibody induction.     

Differential signal transduction via T-cell receptor CD3 zeta 2, CD3 zeta-eta, and CD3 eta 2 isoforms.

The T-cell antigen receptor (TCR) consists of an antigen-binding heterodimer, termed Ti, which is noncovalently associated with the invariant CD3 subunits (gamma, delta, epsilon, zeta, and eta). The CD3 zeta and -eta subunits form either homodimeric or heterodimeric structures in turn associated with the other components of the TCR complex. This feature increases the structural complexity of TCRs by creating "isoforms." Both CD3 zeta and -eta are thought to play an important role in signal transduction triggered by antigen/major histocompatibility complex. To compare signaling functions of TCR isoforms, MA5.8, a CD3 zeta-eta- variant of the cytochrome c-specific, I-Ek-restricted T-cell hybridoma 2B4.11, was stably transfected with cDNAs encoding CD3 zeta and/or CD3 eta, and resulting clones were characterized. The findings indicate that signals inducing Ca2+ mobilization, phosphatidylinositol turnover, and interleukin 2 production are each transmitted by the above TCR isoforms. In contrast, tyrosine phosphorylation of the CD3 zeta subunit but not the CD3 eta subunit follows TCR stimulation. Given the general importance of tyrosine phosphorylation for receptor signaling, it is likely that this difference between TCR isoforms plays a regulatory role in T-lineage function by qualitatively or quantitatively altering signaling events.