Relative efficacy of long-acting stimulants on children with attention deficit-hyperactivity disorder: a comparison of standard methylphenidate, sustained-release methylphenidate, sustained-release dextroamphetamine, and pemoline.

Twenty-two children with attention deficit-hyperactivity disorder underwent a double-blind, placebo-controlled, crossover evaluation of the efficacy of standard methylphenidate twice a day and comparable doses every morning of a sustained-release preparation of methylphenidate (SR-20 Ritalin), a sustained-release form of dextroamphetamine (Dexedrine Spansule), and pemoline. The children were participating in a summer treatment program in which they engaged in recreational and classroom activities. Dependent measures include evaluations of social behavior during group recreational activities, classroom performance, and performance on a continuous performance task.

Recognition of cluster of differentiation 1 antigens by human CD4-CD8-cytolytic T lymphocytes.

Human cluster-of-differentiation 1 (CD1) is a family of cell surface glycoproteins of unknown function expressed on immature thymocytes, epidermal Langerhans cells and a subset of B lymphocytes. Three homologous proteins, CD1a, b and c, have been defined serologically, and the CD1 gene locus on human chromosome 1 contains five potential CD1 genes. Analysis of the predicted amino-acid sequences of CD1 molecules reveals a low but significant level of homology to major histocompatibility complex (MHC) class I and class II molecules, and, like MHC class I molecules, CD1 molecules are associated non-covalently with beta 2-microglobulin.

Developmental regulation of erythropoiesis by hematopoietic growth factors: analysis on populations of BFU-E from bone marrow, peripheral blood, and fetal liver.

Fetal hematopoiesis is characterized by expanding erythropoiesis to support a continuously increasing RBC mass. To explore the basis for this anabolic, nonhomeostatic erythropoiesis, the proliferative effect of recombinant hematopoietic growth factors on highly enriched hematopoietic progenitor cells from fetal and adult tissues were compared. Fetal hepatic BFU-E, unlike adult bone marrow (BM) or peripheral blood (PB) BFU-E, were capable of proliferating in response to erythropoietin in the absence of added GM colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), and erythropoietin (Epo) directly stimulated the expansion of the fetal BFU-E pool in suspension culture.

Requirements for modulation of the CD4 molecule in response to phorbol myristate acetate. Role of the cytoplasmic domain.

CD4 (T4) is a 60 kD glycoprotein expressed on a subset of T lymphocytes. CD4 augments T cell responses to suboptimal Ag stimulation. In addition, the CD4 molecule is the receptor for HIV-1.

Studies on protein methyltransferase in human cerebrospinal fluid.

Protein methyltransferases, rich in most mammalian brains, were studied in human cerebrospinal fluid (CSF). Among several well-characterized groups of methyltransferases, protein methylase I (S-adenosylmethionine:protein-arginine N-methyltransferase, EC 2.1.

Inhibition of CD4+ T cell function by the HIV envelope protein, gp120.

The CD4 molecule is functionally involved in the class II MHC-restricted T cell response to Ag. CD4 is also the receptor for HIV-1, the major etiologic agent of AIDS. We have assessed whether the interaction of the HIV-1 envelope protein with the CD4 molecule might interfere with the normal function of CD4, thereby contributing to the immunosuppression observed after HIV infection.

Lymphocytotoxic antibodies in systemic lupus erythematosus: studies of their temperature dependence, binding characteristics, and specificity in vitro.

The lymphocytotoxicity of 33 lupus sera was tested against purified helper/inducer (OKT4) and cytotoxic/suppressor (OKT8) subsets of T lymphocytes at 15 degrees C and 37 degrees C in vitro. There was significantly less killing of both OKT4 and OKT8 cells at 37 degrees C (p less than 0.001 and p less than 0.

Functional analysis of a cytoplasmic domain-deleted mutant of the CD4 molecule.

The CD4 molecule is a receptor found on a subset of T lymphocytes. It has been proposed that, upon binding MHC class II molecules expressed on APC, the CD4 molecule enhances the responsiveness of the T cell by increasing intercellular avidity and/or by transducing an intracellular signal. We have analyzed the effect of removing the cytoplasmic domain of the CD4 molecule on the ability of the CD4 molecule to enhance T cell responsiveness.

Expression and function of CD8 in a murine T cell hybridoma.

In general, the human CD8 molecule is expressed on T cells specific for HLA class I molecules. Studies designed to delineate the function and to define the ligand of the CD8 molecule have been complicated by the fact that the presumptive ligand for CD8 is on the HLA class I molecule, the same molecule encoding the ligand for the antigen-specific T cell receptor. The ability to express genes in cells other than their natural host has produced a new technology with which to approach CD8 functional studies.

Expression and function of CD4 in a murine T-cell hybridoma.

The CD4 (T4) antigen was originally described as a phenotypic marker specific for helper T cells, and has recently been shown to be the receptor for the human immunodeficiency virus (HIV). Functional studies using monoclonal antibodies directed at CD4 and major histocompatibility complex (MHC) class II molecules led to the suggestion that CD4 binds to the MHC class II molecules expressed on stimulator cells, enhancing T-cell responsiveness by increasing the avidity of T cell-stimulator cell interaction and/or by transmitting a positive intracellular signal. But recent evidence that antibodies to CD4 inhibit T-cell responsiveness in the absence of any putative ligand for CD4 has been interpreted as suggesting that antibody-mediated inhibition may involve the transmission of a negative signal via the CD4 molecule instead.

The role of the L3T4 molecule in mitogen and antigen-activated signal transduction.

We investigated the role of the L3T4 molecule in mitogen and antigen-initiated signal transduction in the L3T4(+) murine T cell hybridoma, 3DT52.5.9 and an L3T4(-) variant, 3DT52.

Phase coherence in vibration-induced responses of tactile fibres associated with Pacinian corpuscle receptors in the cat.

1. In pentobarbitone-anaesthetized cats, responses were recorded in peripheral nerves or cervical dorsal columns from sensory fibres associated with Pacinian corpuscle (P.c.

Distinct roles for L3T4 in T cell activation.

The mutually exclusive expression of L3T4 and Lyt-2 on murine T cells and the correlation of their expression to the major histocompatibility complex (MHC) restriction of the T cell antigen receptor (Ti) have led to the hypothesis that these surface molecules are related to recognition of class II and class I MHC antigens, respectively. It has been suggested that these T cell surface molecules interact with nonpolymorphic determinants on MHC antigens. We have studied the role of L3T4 in activation of an H-2Dd-specific T cell hybridoma.

Alpha interferon clinical trial for multiple sclerosis: design considerations.

The design and course of a placebo-controlled alpha-2 interferon trial in MS patients are described. No beneficial effect of the interferon on the course of MS could be shown.

Systemic recombinant alpha-2 interferon therapy in relapsing multiple sclerosis.

This report describes the first use of recombinant-DNA-produced human interferon in patients with multiple sclerosis (MS). Ninety-eight patients who were clinically definite for MS with two or more documented exacerbations during the preceding two years were admitted to this placebo-controlled double-blind randomized trial. Although both groups were similar, placebo patients had later MS onset.

Requirement for three distinct lymphokines for the induction of cytotoxic T lymphocytes from thymocytes.

The induction of cytotoxic T lymphocytes (CTL) from CTL precursors requires a combination of antigen and lymphokine signals. To investigate lymphokine requirements for CTL generation, we used an assay in which helper T cell and accessory cell-depleted spleen cells or whole thymocytes were cultured with lectin (Con A) and lymphokines. This culture was followed by assessment of lectin-dependent cytolysis.

Characterization of antigen-specific T cells in multiple sclerosis twins with elevated proliferative responses to measles virus.

The proliferative response to measles virus in normal individuals is low compared with the response to mumps virus. This is probably due to a low precursor frequency of OKT4+, IL 2-secreting helper cells. The presence of a measles high-responder state has previously been identified in some twin individuals with multiple sclerosis.

The mechanism of antigen presentation by dendritic cells and splenic adherent cells in the induction of an allogeneic cytotoxic T-lymphocyte response to H-2Kk liposomes.

Induction of an allogeneic cytotoxic T-lymphocyte (CTL) response to purified alloantigen is partially dependent on uptake and processing of the class I alloantigen by antigen-presenting cells (APC) followed by recognition of the alloantigen and self Ia by helper T cells (TH). The activated TH provides the helper signal(s) to the alloantigen-specific CTL for proliferation and differentiation into an active effector CTL. The role of antigen processing and presentation of major histocompatibility complex alloantigens was examined and the ability of different types of APC to present purified H-2Kk liposomes was investigated.

The role of T cell accessory molecules in the generation of class II-specific xenogeneic cytolytic T cells.

In the generation of allogeneic, hapten-modified and virus-specific cytotoxic T cell (CTL) responses there is usually a requirement for T-T interaction between the T helper cell (TH) and the precursor CTL (CTL). We have investigated the role of a TH signal in the induction of a xenogeneic mouse antihuman CTL response by using membranes and liposomes bearing the xenogeneic antigen to stimulate primed responders. The TH signal can be achieved by either an Ia-restricted, L3T4+ DR-specific T cell or by the addition of nonspecific T helper factors(s).

Recognition of the alpha-1 and alpha-2 domains of H-2 molecules by allospecific cloned T cells.

Previously we had shown that allospecific bulk cultures of cytolytic T lymphocytes lysed the products of cloned class I major histocompatibility genes expressed after DNA-mediated gene transfer. In these experiments, performed by using cloned allospecific T cell effectors, a T cell hybridoma, and recombinant DNA technology, we have been able to map determinants recognized by these T cell clones to the alpha-1 domain of H-2Dd and the alpha-2 domain of H-2Ld (four of eight clones). Target cells used were L cells (H-2k), expressing wild type or hybrid H-2 antigens of H-2d origin.

The ability of Ia and H-2Kk-bearing membranes to replace the antigen-presenting cell in an H-2Kk allogeneic cytotoxic T cell response.

Induction of an allogeneic cytotoxic T lymphocyte (CTL) response is dependent, in part, on uptake and processing of the class I alloantigen by antigen-presenting cells and subsequent Ia-restricted recognition of the alloantigen by helper T cells, resulting in lymphokine production. The nature of the antigen-processing event has been investigated using reconstituted membranes to replace the antigen-presenting cells in the generation of a secondary allogeneic CTL response. Membranes were isolated from an Iad-positive antigen presenting B cell lymphoma (D2N), detergent solubilized and then reconstituted together with affinity-purified H-2Kk antigen in the presence of protease inhibitors.