Impaired in vivo and in vitro antibody responses to bacteriophage phi X 174 in juvenile rheumatoid arthritis

Immunologic abnormalities described in juvenile rheumatoid arthritis (JRA) have been largely confined to mitogen or antigen driven proliferation assays. We studied antigen specific antibody production using the neoantigen bacteriophage phi X 174 in vivo and in vitro; defective responses were found in all 8 patients with JRA studied. These could not be attributed to circulating anti-T cell antibodies, but may relate to lymphocyte subset abnormalities found by 2 color analyses. These immunologic aberrations may play a direct role in the pathogenesis of JRA or, alternatively, may be a secondary event.     

Serial neuropsychological studies of a child with acute lymphoblastic leukemia and subsequent glioblastoma multiforme

A 10-year-old boy had a right posterior parietal glioblastoma 5 years after completing treatment for acute lymphoblastic leukemia. Interim findings included seizures, leukoencephalopathy, diffuse mineralizing microangiopathy, and abnormal changes in neuropsychological test performance, which, in retrospect, provided information about the location of the tumor. This case highlights unusual sequelae of childhood leukemia and its treatment, as well as the value of neuropsychological procedures in assessing functional status and integrity of the brain.     

Mutations of the Wiskott–Aldrich Syndrome Protein affect protein expression and dictate the clinical phenotypes

Mutations of the Wiskott–Aldrich Syndrome Protein (WASP) are responsible for classic Wiskott–Aldrich Syndrome (WAS), X-linked thrombocytopenia (XLT), and in rare instances congenital X-linked neutropenia (XLN). WASP is a regulator of actin polymerization in hematopoietic cells with well-defined functional domains that are involved in cell signaling and cell locomotion, immune synapse formation, and apoptosis. Mutations of WASP are located throughout the gene and either inhibit or disregulate normal WASP function. Analysis of a large patient population demonstrates a strong phenotype–genotype correlation. Classic WAS occurs when WASP is absent, XLT when mutated WASP is expressed and XLN when missense mutations occur in the Cdc42-binding site. However, because there are exceptions to this rule it is difficult to predict the long-term prognosis of a given affected boy solely based on the analysis of WASP expression.     

The subacute effects of CNS prophylaxis for acute lymphoblastic leukemia on neuropsychological performance: a comparison of four protocols.

We report an assessment of the intellectual functioning after one year of therapy of 117 children treated for acute lymphoblastic leukemia (ALL) who were assigned to one of four protocols for central nervous systems (CNS) prophylaxis. These protocols were (a) 2400 rad cranial irradiation plus concurrent intrathecal methotrexate (i.t. MTX), (b)i.t. MTX alone, (c) 1800 rad cranial irradiation plus concurrent i.t. MTX, and (d) a protocol for high-risk patients that included intensive systemic chemotherapy plus 2400 rad delayed irradiation. Neuropsychological evaluation consisted of the Wechsler intelligence scales, the Wide Range Achievement Test, and selected tests from the Halstead-Reitan Neuropsychological Battery administered one year after diagnosis. All patients performed in the average range on measures, although the high-risk patients performed marginally worse than did the others. In general, our results do not support previous reports that cranial irradiation results in early adverse neuropsychological sequelae.     

Correction of equine severe combined immunodeficiency by bone marrow transplantation

A 32-day-old horse with severe combined immunodeficiency was transplanted with equine bone marrow cells in an attempt to establish immunologic responsiveness. A histocompatible, mixed-leukocyte-culture-nonreactive, sex-matched, full sibling was used as the donor. Recipient total lymphocyte count, T and B lymphocyte numbers, and response of peripheral blood mononuclear cells to phytolectin stimulation increased by 14 days following transplantation. Circulating lymphocytes exceeded 1000 cells/microliter blood by 40 days posttransplantation, and by 170 days following transplantation, T and B lymphocyte numbers had reached normal values. The foal demonstrated significant primary and secondary antibody responses when immunized with bacteriophage phi X 174 at 100 and 142 days posttransplantation. Concentrations of IgG and IgM remained within the normal range following cessation of i.v. plasma therapy 156 days after transplantation. More than 300 days following transplantation, the foal remains healthy and is growing normally. At no time during the posttransplant period was there detectable evidence of graft-versus-host disease.     

Venous clots: evaluation with MR imaging

In vitro and in vivo studies were performed to determine the proton relaxation and imaging characteristics of static blood and acute and organized clot in canine jugular veins. In vivo, it was found that two inversion recovery sequences using a short inversion time (100 msec) demonstrated better differentiation of signal intensity of intravascular clot from surrounding soft tissues than did standard T1- and T2-weighted sequences. In vitro, quantitative measurements showed marked reduction of both T1 and T2 relaxation time of acute clot compared with stagnant blood. In addition, the T1 relaxation time, and to a lesser extent the T2 relaxation time, shortened as the clot aged, indicating a potential role for magnetic resonance imaging in determining the age of venous thrombi.     

Influence of propranolol coadministration or cigarette smoking on the kinetics of desmethyldiazepam following intravenous clorazepate

Summary The influence of propranolol coadministration or of cigarette smoking on the kinetics of desmethyldiazepam following a single 20-mg intravenous dose of clorazepate dipotassium was evaluated in healthy volunteers. In Study One, intravenous clorazepate was given once in the control condition, and again during coadministration of propranolol, 80 mg twice daily. Compliance with the prescribed propranolol regimen was verified by measurement of serum propranolol concentrations (mean, 37 ng/ml). In control vs propranolol treatment conditions, there was no significant difference in desmethyldiazepam volume of distribution (1.27 vs 1.23 liters/kg) or in free fraction in serum (1.83 vs 1.80% unbound). There was a small although statistically significant prolongation of desmethyldiazepam half-life (55 vs 61 h,P<0.05) and reduction in clearance (0.281 vs 0.247 ml/min/kg,P<0.02) attributable to propranolol. In Study Two, desmethyldiazepam kinetics were compared in eight cigarette smokers (mean, 19 cigarettes/day) and in 11 nonsmoking controls matched for age, sex, and body weight. There was no significant difference between controls and cigarette smokers in desmethyldiazepam volume of distribution (1.29 vs 1.34 liters/kg), elimination half-life (55 vs 59 h), clearance (0.284 vs 0.276 ml/min/kg), or free fraction in serum (1.96 vs 1.92% unbound). Thus, propranolol slightly although significantly impairs the clearance of desmethyldiazepam and prolongs its halflife. Cigarette smoking has no apparent influence on desmethyldiazepam kinetics.Supported in part by grants Oc 10/6–4 from the Deutsche Forschungsgemeinschaft and grants MH-34223 and AG-00106 from the United States Public Health ServicePart of doctoral thesis J. Weinbrenner, Bonn 1986     

Immunologic responses to bacteriophage ϕX 174 in immunodeficiency diseases

Immunologic responses to bacteriophage varphiX 174 were studied in 26 patients with immunodeficiency diseases. In eight cases of infantile X-linked agammaglobulinemia, there was prolonged circulation of phage and no detectable antibody response. The remaining 18 patients cleared phage normally and produced antibodies. 10 of these patients made only IgM antibody in spite of repeated immunization; all of these have recurrent respiratory tract infections and require treatment with gamma globulin and antibiotics. Eight patients made both IgM and IgG antibody; they experience either milder or no infections, and only one requires treatment with gamma globulin.Prolonged circulation of bacteriophage varphiX 174 and the absence of a detectable antibody response appear to be distinguishing characteristics of X-linked agammaglobulinemia if severe combined immunodeficiency can be excluded.