Proteinuric renal disease in children in South-Western Uganda.
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Adolescent↗
Biomedical subjects
J Kiwanuka
Publications and source records attributed to J Kiwanuka.
Diagnosis of pulmonary tuberculosis in children in an HIV-endemic area, Malawi.
The diagnosis of pulmonary tuberculosis (PTB) in young children is particularly complex in resource-poor regions where HIV infection is common. This study examines the impact of HIV infection on diagnosis in children with suspected PTB attending Queen Elizabeth Central Hospital, Blantyre. A total of 110 children (4 months-14 years) were studied over a 4-month period. Clinical data were recorded and investigations included Mantoux test, chest X-ray, HIV status (HIV-PCR when younger than 18 months) and sputum, if available. Laryngeal swabs were compared with sputa or gastric aspirates in a subgroup of 60 children. All children were commenced on anti-TB therapy and followed for treatment response. Aware of the clinical overlap between HIV and TB infection, we used more limited criteria than recommended to allocate a final diagnosis following review of all data except HIV status. Final diagnosis included confirmed PTB (n = 8), probable PTB (n = 41), lymphocytic interstitial pneumonitis (n = 10), pulmonary Kaposi sarcoma (n = 3) and bronchiectasis (n = 5). Culture rates of M. tuberculosis were: five (27.8%) of 18 sputa, three (7.1%) of 42 gastric aspirates and four (6.6%) of 60 laryngeal swabs. The HIV infection rate was 70.6% overall and 57.8% in 45 children with confirmed or probable PTB. Although a positive contact history was more common in HIV-infected children, a final diagnosis of confirmed or probable PTB was less common than in HIV-uninfected children (36% vs 63%; p = 0.02). The Mantoux test was positive in 14 (19%) of 72 HIV-infected compared with 15 (50%) of 30 HIV-uninfected children (p < 0.01). A final diagnosis could not be made in 43 (39%) of the study children with suspected PTB, the majority of whom were HIV-infected. HIV-infected children had a significantly poorer response to TB treatment and higher lost-to-follow-up rates.
Adolescent↗
Heterotransplantation of human Burkitt's lymphoma cell lines in athymic nude mice: tumor-host relationships.
We have explored the factors which influence tumorigenicity of Burkitt's lymphoma (BL) cell lines in athymic nude mice. Four cell lines, Namalwa, CA46, JD38, and ST486 revealed tumor incidence of 63.5, 69.0, 45.5 and 10.0%, respectively, in nude mice, but there was no correlation between tumor incidence and growth rate in vivo. Thus, growth rate and tumorigenicity are dependent upon different biochemical pathways. Evidence of tumor cell heterogeneity was demonstrated in the CA46 parent cell line. Five subclones derived from CA46 revealed varying degrees of tumor incidence (but very similar growth rates) that were consistently less than the parent CA46 line. Line 5, for example, produced 5.7-fold less tumors than the parent line. None of the BL cell lines or clones produced any metastatic lesions in liver, lung, brain, bone marrow or spleen in athymic nude mice. Northern blot analysis of c-myc mRNA levels in different BL cell lines revealed a possible relationship between percent tumor takes (but not growth rates) and the level of c-myc oncogene expression. However, no correlation was observed between c-myc mRNA levels and tumor incidence or growth rates among the CA46 clones. There was no correlation between the ability of the cell lines and the subclones to either secrete growth factors or to respond to growth factors secreted by Epstein-Barr virus-induced lymphoblastoid cells or lipopolysaccharide-activated monocytes, and their growth rates or percent tumor takes in mice. Comparison of tumor incidence and growth rates in irradiated and unirradiated mice showed that host factors influenced the growth of BL in nude mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Autoimmune neutropenia and Hodgkin's disease: successful treatment with intravenous gammaglobulin.
We describe a child with Hodgkin's disease (HD) who presented with profound neutropenia, secondary to an antineutrophil antibody. The patient responded to intravenous immunoglobulin (IVIG), with prompt and sustained improvement in total white blood cell count (WBC) and absolute neutrophil count (ANC). The literature pertaining to autoimmune cytopenias complicating HD is reviewed, as well as the role of IVIG in management of these disorders.
Autoimmune Diseases↗
Immunoglobulin delta expression in Burkitt's lymphoma cell lines.
Eighteen Burkitt's lymphoma (BL) cell lines were analyzed for rearrangement and expression of the delta gene. None had rearrangement of the delta gene locus within the 9.0-kb BamHI restriction fragment. Cell lines that expressed the delta gene contained both mu alleles, with at least one productively rearranged. Thirteen of 18 cell lines had detectable transcripts hybridizing with the delta probe. In 10 of the 13 cell lines with delta transcripts, cytoplasmic delta chains were detected, but only two of these expressed delta chains strongly on the surface. All 13 lines made cytoplasmic mu chains, and all except one made cytoplasmic light chains. Surface IgM was detected in all except two of the 13 cell lines. Although BL has generally been considered not to express IgD, except in occasional cases, previous studies have been confined to examination of the cell surface. Many of the cell lines that we examined express delta mRNA transcripts as well as produce cytoplasmic delta chains but no detectable surface IgD. This suggests that delta chains are detectable in the cytoplasm prior to being apparent on the surface. Our findings argue against an origin of BL from germinal center cells since IgD is almost totally lacking in normal B cells present in germinal centers.
Africa↗
Antiimmunoglobulin inhibition of Burkitt's lymphoma cell proliferation and concurrent reduction of c-myc and mu heavy chain gene expression.
We have demonstrated that polyvalent antiimmunoglobulin antibodies directed at appropriate cell surface light (L) or heavy (H) immunoglobulin (Ig) chains will inhibit proliferation and the expression of c-myc and mu-Ig chain mRNA in Burkitt's lymphoma (BL) cell lines bearing 8;14 chromosomal translocations. This effect was not observed in BL cell lines bearing 8;22 translocations or in BL cell lines which did not express surface Ig or in karyotypically normal Epstein-Barr virus-transformed lymphoblastoid cell lines. The antiproliferative effect was reproducible and resulted in cell death in the most sensitive cell lines. The decrease in gene expression preceded the antiproliferative effect. The effect of anti-Ig on gene expression was relatively specific since the level of total (shown by Northern blots) and cytoplasmic (dot blots) mRNA of several other genes (beta-actin, G6PD, kappa-L chain) and the first exon of c-myc (in cell lines in which this exon is expressed separately from the second and third exons) was not changed in these same BL cell lines. Expression of both c-myc and mu was maximally inhibited between 3 and 6 h after the addition of anti-Ig. In the most sensitive BL cell line, concurrent reduction in c-myc and mu mRNA was noted as early as 1 h after anti-Ig and the nadir of expression of these genes occurred at 3 h. These results indicate that the deregulated high constitutive expression of c-myc in some BLs can be down-regulated by anti-Ig resulting in inhibition of proliferation and cell death. In addition these data are consistent with the possibility that in at least some 8;14 bearing BLs the malignant transformation occurs in an immature B-cell undergoing antigen-independent differentiation.
Antibodies↗
Significance of chromosome 8 breakpoint location in Burkitt's lymphoma: correlation with geographical origin and association with Epstein-Barr virus.
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Burkitt Lymphoma↗
Soluble interleukin-2 receptor levels in patients with undifferentiated and lymphoblastic lymphomas: correlation with survival.
We have been able to detect soluble interleukin-2 receptors (IL-2R) in pretreatment sera from 80 patients with undifferentiated lymphoma (predominantly Burkitt's lymphoma) and lymphoblastic lymphoma. The demonstration of IL-2R in lymphoma-derived cell lines by immunoprecipitation and direct staining indicates that IL-2R is synthesized by the tumor cells. Comparisons were made with two other subject groups: 42 sarcoma patients and 17 normal individuals. The distribution of soluble IL-2R values for lymphoma patients (geometric mean, 1,132 U/mL) was significantly greater than that of sarcoma patients (geometric mean, 332 U/mL; P = .0001) or normal individuals (geometric mean, 238 U/mL; P = .0001). Patients with undifferentiated lymphoma stages B, C, and D had significantly higher soluble IL-2R values (geometric mean, 1,648 U/mL) than stages A and AR (geometric mean, 706 U/mL; P = .0001) or lymphoblastic lymphoma (geometric mean, 826 U/mL; P = .0002). Within the lymphoma group, the soluble IL-2R level was found to be the most significant prognostic indicator of disease-free interval and survival when compared with other previously recognized factors such as histology, stage, bone marrow involvement at presentation, lactic dehydrogenase (LDH), uric acid (UA), and age. No factor was significantly associated with response to therapy, ie, the initial achievement of complete remission (CR) status, although small numbers of patients with a partial response limit interpretation. Soluble IL-2R levels were measured serially in two patients and were found to be elevated at presentation or relapse and to decrease to normal levels during periods of disease remission. IL-2R appears to reflect tumor burden and may prove to be a useful and specific marker for lymphoid tumors.
Adolescent↗
Chronic ITP terminating in aplastic anemia.
A 14-year-old white male developed gastric anemia with normal chromosomes following a 6-year history of chronic ITP refractory to splenectomy. The disorder was partially responsive to oxymethalone which was discontinued because of hepatotoxicity. Antiplatelet and antigranulocyte antibodies were identified in the patient's sera. Absorbed sera suppressed normal marrow CFU-C and CFU-E. This case may represent a single-entity autoimmune mechanism characterized initially by thrombocytopenia followed by pancytopenia.
Adolescent↗