In vitro preactivated human T cells engraft in SCID mice and migrate to murine lymphoid tissues.

Mice with severe combined immunodeficiency (SCID) accept grafts of human T and B lymphocytes derived from resting peripheral blood mononuclear cells (PBMC). We wished to determine whether activated human T cells engraft and migrate into lymphoid tissues in SCID mice. PBMC (50 x 10(6)) activated in vitro in a 4-day mixed lymphocyte culture (MLC) were injected into the peritoneum of 12 SCID mice. In 11 of 12 animals killed at 3 or 4 weeks after injection, human cells were detected in cells pooled from lymphoid organs by flow cytometry and by immunohistochemical staining of frozen tissue sections. The percentage of CD45+ cells in the 11 mice ranged from 2% to 45% and the absolute numbers of CD45+ cells recovered from lymphoid organs ranged from 4 x 10(6) to 90 x 10(6). Up to 93% of the human cells expressed the CD3 antigen together with either CD4 or CD8. Human T cells were localized in periarteriolar areas in murine spleens, whereas in the lymph nodes and gut mucosa, the T cells did not show the pattern for T-dependent areas found in human lymphoid tissue. Numerous human plasma cells were detected in the spleen and gut mucosal crypts of engrafted SCID mice. Human IgG was detected in the serum of all 11 engrafted SCID mice. The functional activity of human T cells recovered from murine splenic tissue was very low 3-4 weeks after engraftment.     

Minimising stimulator artefacts in electromagnetic flow signals

Simultaneous electrical stimulation of tissue with the measurement of blood flow using an electromagnetic flowmeter system almost invariably results in large flow measurement inaccuracies. These inaccuracies are because the electrical energy from stimulating artefacts is amplified along with the flow signals. The paper describes the building and use of an inexpensive circuit to remove stimulation artefacts from electromagnetic flow measurements.     

Electromyographic and affective responses of episodic tension-type headache patients and headache-free controls during stressful task performance

Thirty-four subjects meeting diagnostic criteria for episodic tension-type headache and 42 who rarely experienced headaches participated in two laboratory sessions in which cephalic electromyographic (EMG) activity, electrodermal activity, heart rate, and finger temperature were recorded. Subjects performed relaxation, choice reaction time, psychomotor tracking, voluntary muscle contraction, and cold pressor tasks. Headache subjects showed significantly greater EMG activity than controls during baseline and stressful task performance. During relaxation, both groups reduced EMG activity from baseline levels, and there was no significant difference in EMG level between the groups during relaxation. Headache subjects reported higher levels of subjective anxiety, depression, anger, and stress than controls. Headache subjects also reported higher levels of pain than controls, and headache subjects reported greater pain during stressful task performance relative to baseline and recovery periods.This research was supported by NIH Grant R01-NS-25114.     

Methylphenidate and dextroamphetamine treatments of hyperactivity: are there true nonresponders?

The response to stimulant drugs of 48 boys with attention deficit/hyperactivity disorder was measured following dextroamphetamine, methylphenidate, and placebo in a double-blind crossover study. To distinguish lack of behavioral improvement from adverse drug effects, a day hospital setting and a wide dose range were used. Both drugs were highly and equally efficacious for the group as a whole, and frequently one drug or the other was superior for an individual child, or adverse effects occurred only on one of the stimulants. Only one of the 48 boys (2%) was discharged without the recommendation for continued stimulant drug treatment. "Nonresponse" appears to be extremely rare when both stimulants and a wide range of doses are given.     

Differential effects of methylphenidate and dextroamphetamine on the motor activity level of hyperactive children

An acceleration-sensitive device was used to measure motor activity continuously through the day in 18 hyperactive boys in a day hospital program. The children received methylphenidate, dextroamphetamine, or placebo daily after breakfast and lunch in an 11-week double-blind crossover trial. Differential effectiveness of the two drugs in lowering motor activity was found. Methylphenidate significantly lowered activity measurements in a morning structured classroom and in less structured activities in the afternoon. Dextroamphetamine effects on activity were similar, although they did not differ significantly from placebo effects between 11:00 AM and noon in our classroom setting. Methylphenidate produced a greater decrement in motor activity than did dextroamphetamine between 11:00 AM and 1:00 PM. There were no significant differences in activity level between drug doses within each drug phase across the dose ranges used (for methylphenidate 0.45 to 1.25 mg/kg given twice daily, and for dextroamphetamine 0.2 to 0.6 mg/kg given twice daily). Plasma drug concentrations did not correlate with decrements in activity for either drug.     

T-Lymphoblasts with Erythropoietic Helper Function in Acute T-Cell Leukemia

A patient with acute T-lymphoblastic leukemia was found to maintain a normal hemoglobin concentration both at presentation and preterminally several months later, despite a replaced bone marrow and over 80% circulating lymphoblasts on both occasions. Cell surface marker analysis demonstrated the T-lymphoblasts both at presentation and preterminally to belong to the T-helper subpopulation. In vitro culture studies demonstrated that the patient's T-lymphoblasts, as well as conditioned medium derived from these lymphoblasts, significantly stimulated normal bone marrow erythroid colony growth (CFU-E). These findings suggest that in this patient the preservation of erythropoiesis resulted from a helper effect exerted by his T-lymphoblasts.     

Acute B-lymphocytic leukemia with L1 morphology: a report of two pediatric cases

Two pediatric cases of acute lymphoblastic leukemia with L1 morphology who also demonstrated immunoglobulin on the leukemic cell surface are presented. The first patient's disease progressed on standard induction therapy, despite the presence of good prognostic features at presentation. The second patient has achieved a sustained remission with an aggressive lymphoma regimen. These two cases represent the first report on the outcome of patients with this rare phenotype. They indicate the importance of assessing cell surface immunoglobulin in children with acute leukemia, even in the absence of the L3 phenotype, in addition to the currently utilized batteries of monoclonal antibodies. Failure to recognize this phenotype may have significant therapeutic implications.     

Autoimmune hemolytic anemia as a manifestation of T-suppressor-cell deficiency

This report describes two children in whom autoimmune hemolytic anemia was the initial clinical manifestation of an underlying T-cell deficiency. Further investigation revealed a profound deficiency of T suppressor cells in both children as detected by monoclonal T-cell antibody (OKT8) and/or functional assays. In vitro incubation of their lymphocytes with cultured thymus epithelium or thymic factors induced T suppressor cells. In vivo treatment with cultured thymus epithelium or calf thymosin fraction 5 resulted in increased T-suppressor-cell numbers and/or function in both and possibly decreased hemolytic activity in one. These results suggest that the autoimmune process in some patients with autoimmune hemolytic anemia is associated with T-suppressor-cell deficiency and that in vivo therapy with agents that modulate T-cell function may be of therapeutic value.