Plasma zinc levels inversely correlate with vascular cell adhesion molecule-1 concentration in children with sickle cell disease.

Zinc deficiency has been implicated in impaired cell-mediated immunity of children with sickle cell disease (SCD). However, its influence on the expression of vascular cell-adhesion molecule-1 (VCAM-1) on endothelial cells, a protein involved in vasoocclusion, has not been previously investigated. We therefore measured (soluble) sVCAM-1 and zinc in 76 SCD children and 96 non-SCD children, mean age 7.73 years and 11.24 years, respectively. Although mean zinc levels of both groups were within the normal range (approximately 14.5 micromol/l), 14.5 % of SCD and 11% of non-SCD children (without inflammation) had levels below normal (10.7 micromol/L). Mean sVCAM-1 concentrations of SCD children (837 microg/l) were significantly higher than those of controls (627 microg/l) (p < 0.001). Differences persisted after taking into account age, hemoglobin phenotype, and inflammation (alpha-l acid glycoprotein >l g/l and C-reactive protein >10 mg/I). sVCAM-1 negatively correlated with serum (r = -0.444) and red blood cells zinc (r = -0.242, p < 0.05) but not with acute-phase proteins. Mean sVCAM-1 tended to be higher in SCD children with than in those without a history of a health problem (infection, pain crisis or were transfused; not significant). Data suggest that zinc may modulate the clinical status of SCD children through VCAM-1 expression, and zinc supplementation may be beneficial in these patients.

Differential effects of hydroxyurea and zileuton on interleukin-13 secretion by activated murine spleen cells: implication on the expression of vascular cell adhesion molecule-1 and vasoocclusion in sickle cell anemia.

BACKGROUND: Interleukin-13 (IL-13), a TH2 cytokine, upregulates the expression of vascular cell adhesion molecule-1 on endothelial cells, a factor involved in vasoocclusion in sickle cell disease (SCD). Hydroxyurea improves clinical status of SCD patients in part by induction of fetal hemoglobin. Its effect on IL-13 secretion has not been investigated. OBJECTIVE: To determine whether hydroxyurea and zileuton, a hydroxyurea derivative with antiinflammatory properties, affect IL-13 secretion. METHODS: We measured IL-13 in the supernatant of murine spleen cells incubated without and with hydroxyurea, zileuton (10 microg/ml), concanavalin A (2.5 microg/ml), and anti-CD3 (50 ng/ml) (n=8). RESULTS: Hydroxyurea and zileuton do not affect baseline IL-13 secretion. Unexpectedly, hydroxyurea increases IL-13 levels above baseline (120%, 216.5%, [p<0.05] after 24 h and 48 h, respectively) in lymphocytes activated by anti-CD3, while zileuton reduces them by 59%-78% (p<0.005). In lymphocytes activated by concanavalin A, hydroxyurea and zileuton reduce IL-13 secretion by 24-36% and 50-87%, respectively (p<0.05). Hydroxyurea, but not zileuton, significantly inhibits spleen cell proliferative responses to mitogens (p<0.005). CONCLUSION: Data suggest that hydroxyurea up-regulates IL-13 secretion in anti-CD3-activated lymphocytes through gene activation but not by altered cell proliferation. Increased IL-13 secretion may contribute to unresponsiveness of certain SCD patients to hydroxyurea. The potential benefit of zileuton in the management of vasoocclusion is discussed.

Gamma/delta T-cell lymphoma as a recurrent complication after transplantation.

We present a case of gamma-delta (gammadelta) T-cell lymphoma as a recurrent event in a pediatric liver transplant recipient. Liver transplantation was performed during infancy in an 18-month-old black girl because of cryptogenic cirrhosis. The patient received immunosuppression with cyclosporine and prednisone. Five years after transplantation, the patient was found to have a gammadelta T-cell lymphoma located in retroperitoneal nodes. She received chemotherapy and did well, remaining disease-free for 6 years. She remained only on prednisone for prevention of graft rejection, but was noted to have a non-tender skin nodule that upon biopsy proved to be again a gammadelta T-cell lymphoma. However, comparison of tissue from both tumors revealed that the second occurrence of this malignancy was a de novo event, differing from the first by immunophenotypic and immunohistochemical characteristics, and TCR rearrangement. The patient continues to do well, without evidence of disease recurrence, after being treated again with chemotherapy. A summary of the literature is presented and comparison of our case is made.

Blast crisis of chronic myeloid leukemia: diagnosis prompted by T(8;9).

T(8;9) is a relatively new translocation that has been reported in a few patients with chronic myeloid leukemia (CML) but never in acute myeloid leukemia (AML). We report here a patient who presented with AML with t(8; 9). He lacked the Philadelphia chromosome but tested positive for the gene by the polymerase chain reaction method. This confirmed the diagnosis of CML with blast crisis, and appropriate treatment could be instituted