Michael S. Borzy

Hepatic adenoma in Fanconi anemia treated with oxymetholone

Patient M. L., a white boy, was born in 1962, from a possibly consanguineous union of a 14-year-old primigravida and a 38year-old man. Family history was unavailable. Birth weight, length, and head circumference were compatible with 36, 38, and 321/2 gesiational ~veeks, respectively. Multiple anomalies included short stature, microcephaly, developmental delay, bilateral ocular ptosis, hypoplastic and simplified left pinna with atresia of external auditory canal and hypoplasia of the mastoid bone, micrognathia, hypoplastic testes, hyperpigmentation, cafrau-lait spots, bilateral absence of radii and thumbs, bowed and shortened ulnae, and hypoplastic carpal bones. Urologic studies, done because of ear defects, showed small, dysplastic, and low-set kidneys, with a right pelvic kidney. At age 8 years, polytomograms of petrous ridges confirmed the absence of left external auditory canal and identified normal middle ear bones, round and oval windows, cochlea, and internal auditory canals. Audiogram at age 11 years showed a moderately severe loss of acuity on the left, mostly conductive, with nearly normal bone conduction. Complete blood counts during multiple hospitalizations to correct birth defects were normal until age 5 years, when a platelet count was 50,000/mm 3Following severe bleeding after dental extraction at age 81A years, the diagnosis of Fanconi

Successful bone marrow transplantation with split lymphoid chimerism in DiGeorge syndrome

A female infant with DiGeorge syndrome associated with severe T-cell immunodeficiency underwent a successful bone marrow transplantation from her HLA-identical, mixed leukocyte culture-nonreactive brother at 5 months of age. Mature circulating T cells and mitogen-induced proliferative responses were detectable at 10 days posttransplant, and by 8 months posttransplant functional T- and B-cell reconstitution was documented by normal responses to mitogens and normal levels of serum immunoglobulins as well asin vitro andin vivo T-cell reactivity to specific antigens and production of specific antibody to T cell-dependent antigensin vivo. Phytohemagglutinin-induced interleukin-2 production and cell surface interleukin-2 receptor expression improved posttransplant, with normal production values observed by 8 months posttransplant. Histologic examination of appendix and thoracic lymph node obtained 9 and 17 months posttransplant, respectively, revealed near-normal lymphoid architecture, with germinal center formation providing morphologic confirmation of reconstitution. Stable split lymphoid chimerism with T cells of donor origin and B cells remaining recipient in origin was documented by sex chromosome analysis. Two years posttransplant the subject remains free of serious infections. In conclusion, this case indicates that bone marrow transplantation can produce peripheral immunoreconstitution without need for significant thymic influence, most likely by providing a source of postthymic T cells, and that bone marrow transplantation should be considered a therapeutic option in patients with DiGeorge syndrome associated with severe T-cell deficiency.

Interleukin 2 production and responsiveness in individuals with acquired immunodeficiency syndrome and the generalized lymphadenopathy syndrome

Proliferative responsiveness to, and production of, interleukin 2 (IL-2) was determined in 9 homosexually active men with the acquired immunodeficiency syndrome (AIDS) and in 28 homosexually active men with the persistent generalized lymphadenopathy syndrome (PGL). All were seropositive for antibody to human T-lymphotrophic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). Purified T lymphocytes from individuals with AIDS and PGL had a significantly decreased (P less than 0.01) proliferative response to a saturating amount of exogenous, purified IL-2 as compared to seronegative male controls. Similarly, T4+-enriched T lymphocytes also had a significantly decreased proliferative responsiveness to IL-2 (AIDS, P less than 0.05; PGL, P less than 0.005). T8+-enriched T lymphocytes from individuals with AIDS or PGL did not suppress the IL-2-induced proliferation of autologous T4+ T lymphocytes. In addition, production of IL-2 was significantly decreased in the AIDS group (P less than 0.01) and the PGL group (P less than 0.005) with median values of IL-2 produced being 0.1 and 1.0 U/ml, respectively, compared to 9.9 U/ml for control. These findings demonstrate that substantial quantitative and qualitative abnormalities of the IL-2-T-lymphocyte system exist in patients with AIDS as well as in relatively healthy individuals with PGL. These defects are likely important contributing factors to the depressed T-lymphocyte functions commonly observed in HTLV-III/LAV-associated diseases.

Mixed-Pattern Immune Deposit Glomerulonephritis in a Child With Inherited Deficiency of the Third Component of Complement

The renal histopathology of a 7-year-old Laotian male with inherited deficiency of the third component of complement, recurrent infections, and persistent hematuria and proteinuria is described. The histologic changes are predominantly those of mesangiopathic disease with isolated changes resembling type I membranoproliferative glomerulonephritis and transmembranous glomerulonephritis. IgG, IgA, IgM, C4, and fibrinogen, but not C3, were detected by immunofluorescence in mesangial zones and in segments of capillary walls. A normal distribution of C3b receptors was present along all capillary walls. This report provides additional support for the association of congenital C3 deficiency and immune deposit glomerulonephritis.

Elevated production of interleukin-2 by lymphocytes from children with acute leukemia.

Abnormalities of the production of interleukin-2 (IL-2) may play an important role in the immunologic dysfunction observed in pediatric leukemia patients. For an evaluation of the ability of lymphocytes from leukemic children to produce this cytokine, the production of IL-2 by mitogen-stimulated peripheral blood mononuclear cells was determined in children with acute leukemia at the time of diagnosis, during clinical remission, and at the time of relapse. Of 16 patients, 11 (69%) with either acute lymphoblastic leukemia or acute nonlymphoblastic leukemia at the time of diagnosis had IL-2 production levels above the highest level observed in control subjects, and all but one had values above the control mean. Three of five treated patients had elevated IL-2 production at the time of bone marrow relapse. In addition, of 37 patients examined during clinical remission (both during chemotherapy and after the completion of maintenance chemotherapy), five had IL-2 production values above the control range and four of these five patients subsequently had relapses, compared with only one relapse in the remaining 32 patients with normal or below-normal levels of IL-2 production. These results demonstrate an increased ability to produce IL-2 by many patients with acute leukemia, both at the time of diagnosis and at relapse. Elevated IL-2 production may represent an immunologic response to leukemic cells and in some patients may provide a marker for persistent leukemia.

Indomethacin-Sensitive Monocyte Killing Defect in a Child with Disseminated Atypical Mycobacterial Disease

A child with disseminated disease due toMycobacterium avium had progressive disease in spite of 4.5 years of therapy with multiple antimicrobial agents selected on the basis ofin vitro sensitivity testing of her organism. A defect in monocyte bactericidal activity was detected which was correctedin vitro by exposure of the patients monocytes to indomethacin and normal serum. Indomethacin therapy resulted in normalization of monocyte bactericidal activity and striking, albeit temporary, clinical improvement.

The effects of thymic epithelial monolayer-conditioned medium on suppressor cell function following chemotherapy in pediatric patients

SummaryHuman thymic epithelial monolayer-conditioned medium (TEM-CM) enhanced concanavalin A (ConA)-induced suppressor T-lymphocyte activity in 15 of 17 studies of fractionated light-density bone marrow mononuclear cells (LD-BMMC) obtained from pediatric cancer patients within 7 days of chemotherapy (P<0.001). However, TEM-CM depressed ConA-induced suppressor T-lymphocyte activity in 14 of 18 studies of LD-BMMC obtained from patients who had received their chemotherapy 14–21 days previously (P<0.05). In studies of LD-BMMC from normal subjects, TEM-CM did not show any significant effect on suppressor cell activity, nor did TEM-CM significantly affect spontaneous suppressor cell activity in patients or normals. The effect of direct culture on thymic epithelial monolayers was equivalent to the effect of TEM-CM in both ConA-induced and spontaneous suppressor cell assays. These data demonstrate thymic factor-mediated changes in suppressor T-cell activity of pediatric cancer patients and suggest a postchemotherapy alteration in the bone marrow population of inducible prethymic T cells.