Wen-Jun Weng

Autoimmune Hemolytic Anemia in Patients with β-Thalassemia Major

Hemolysis is a common feature in patients with β-thalassemia major. As a result, autoimmune hemolytic anemia complicating β-thalassemia is easily overlooked. Here, the authors described the clinical features and management of 7 patients with β-thalassemia major and autoimmune hemolytic anemia. These patients had fever, cough, and tea-colored urine on admission. The laboratory investigations showed a significant drop in hemoglobin and increased serum bilirubin. Coombs’ tests revealed that anti-immunoglobulin G (IgG) and anti-C3 was positive in 7 and 5 cases, respectively, whereas anti-Rh E alloantibody was positive in 3 cases. All the patients received corticosteroids treatments and blood transfusions. Patients with anti-Rh E alloantibodies also received immunoglobulin treatments. Six of the patients responded well to the management, but 1 patient developed recurrent autoimmune hemolytic anemia that required cyclosporin A treatment. All the patients remained well by following up for more than 6 months.

Panel reactive antibody in thalassemic serum inhibits proliferation and differentiation of cord blood CD34+ cells in vitro.

Thalassemic children are at a high risk of graft rejection in cord blood transplantation. To investigate this possible mechanism, the authors evaluated the effect of panel reactive antibody on the growth of CD34+ cells in vitro. On semisolid medium, CD34+ cells derived from cord blood were incubated with thalassemic serum, and colony-forming units were counted after 10 days of culture. After incubation with serum-specific panel reactive antibody, profound decreases were found in the numbers of CFU-GM, CFU-GEMM and BFU-E compared with controls. The results indicated that serum-specific panel reactive antibody might have an apparent inhibition effect on proliferation and differentiation of cord blood CD34+ cells.

Pure red cell aplasia associated with cytomegalovirus and Epstein–Barr virus infection in seven cases of Chinese children

Abstract Pure red cell aplasia (PRCA) associated with cytomegalovirus (CMV) and Epstein–Barr virus (EBV) infection is uncommon. Here, we describe the clinical features and management of seven cases of Chinese children with PRCA associated with viral infections. The patients presented with pallor on admission. Blood cell counts and marrow smears showed anemia, reticulocytopenia, and aplasia of erythroblasts. Serological investigation and DNA polymerase chain reactions for CMV were positive in four patients and those tests for EBV were positive in other three patients. All patients received blood transfusion, corticosteroids treatment, and ganciclovir injection. Two patients had a complete response and one had a partial response after the treatments. The other three patients had a complete response to second-line therapies, including high-dose methylprednisolone, cyclosporin A, and intravenous immunoglobulin. Only one patient had no response to the therapies. Our results indicated that it might be important to combine immunosuppressive drugs with an antiviral drug in the management of PRCA associated with CMV and EBV infection.

Synergism between the mTOR inhibitor rapamycin and FAK down-regulation in the treatment of acute lymphoblastic leukemia

BackgroundAcute lymphoblastic leukemia (ALL) is an aggressive malignant disorder of lymphoid progenitor cells in both children and adults. Although improvements in contemporary therapy and development of new treatment strategies have led to dramatic increases in the cure rate in children with ALL, the relapse rate remains high and the prognosis of relapsed childhood ALL is poor. Molecularly targeted therapies have emerged as the leading treatments in cancer therapy. Multi-cytotoxic drug regimens have achieved success, yet many studies addressing targeted therapies have focused on only one single agent. In this study, we attempted to investigate whether the effect of the mammalian target of rapamycin (mTOR) inhibitor rapamycin is synergistic with the effect of focal adhesion kinase (FAK) down-regulation in the treatment of ALL.MethodsThe effect of rapamycin combined with FAK down-regulation on cell proliferation, the cell cycle, and apoptosis was investigated in the human precursor B acute lymphoblastic leukemia cells REH and on survival time and leukemia progression in a non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mouse model.ResultsWhen combined with FAK down-regulation, rapamycin-induced suppression of cell proliferation, G0/G1 cell cycle arrest, and apoptosis were significantly enhanced. In addition, REH cell-injected NOD/SCID mice treated with rapamycin and a short-hairpin RNA (shRNA) to down-regulate FAK had significantly longer survival times and slower leukemia progression compared with mice injected with REH-empty vector cells and treated with rapamycin. Moreover, the B-cell CLL/lymphoma-2 (BCL-2) gene family was shown to be involved in the enhancement, by combined treatment, of REH cell apoptosis.ConclusionsFAK down-regulation enhanced the in vitro and in vivo inhibitory effects of rapamycin on REH cell growth, indicating that the simultaneous targeting of mTOR- and FAK-related pathways might offer a novel and powerful strategy for treating ALL.

Homing and engraftment of bone marrow cells derived from different donors in a murine model of sensitization

Abstract Sensitized recipients are at a high risk of graft rejection in hematopoietic stem cell transplantation. To explore the trace of donor cells, we tried to explore homing and engraftment of bone marrow cells (BMCs) derived from different donors in a murine model of sensitization. Sensitized BALB/c mice were used as transplanted recipients, which received BMCs derived from C57BL/6 or BALB/c donors after lethal irradiation. The homing study showed that the donor cells decreased along with time in recipients of the C57BL/6 donor group, but the donor cells increased along with time in recipients of the BALB/c donor group. For the engraftment assay, all the sensitized recipients transplanted with BMCs derived from C57BL/6 donors died after lethal irradiation. In contrast, all the recipients transplanted with BMCs derived from BALB/c donors got long-term survival. Our results suggest that it is crucial to have human leukocyte antigen identical donors for sensitized recipients during hematopoietic stem cell transplantation.

Evaluation of hepatic iron overload in Chinese children with β-thalassemia major.

Patients with β-thalassemia major require long-term blood transfusions, resulting in hepatic iron overload. Thirty-five Chinese children with β-thalassemia major were recruited in the present studies. Hepatic iron overload was evaluated by histological grading. The relationships between hepatic iron overload and both serum biochemical markers and magnetic resonance imaging (MRI) examination were studied. The majority of the patients showed high degrees of hepatic iron overload by histological study. The degree of hepatic iron overload was correlated with serum ferritin (r = .70, P < .01), hyaluronic acid (r = .58, P = .011), and type III precollagen (r = .55, P = .035). Moreover, hepatic iron overload showed a negative correlation with liver to muscle signal intensity ratio (r = −.44, P = .012), and a positive correlation with red marrow area percentage (r = .52, P < .01). These results indicated that hepatic iron overload might be assessed by serum biochemical markers and MRI examination.

Modified conditioning regimen improves outcomes of unrelated donor peripheral blood stem cell transplantation for β-thalassaemia major patients

The objective of this study was to evaluate the feasibility of a modified conditioning regimen for the treatment of patients with β‐thalassaemia major (TM), using unrelated donor peripheral blood stem cell transplantation (UD‐PBSCT).

A pilot study on detection of PRA in the children with severe -thalassemia using enzyme-linked immunosorbent assay in China.

Aims: To investigate the distribution of food allergens in pediatric allergic rhinitis. Methods: 106 children diagnosed with allergic rhinitis were reviewed and divided into two age groups, including preschooler (2-5 years old) group, 48 cases; and school children group (6-13 years), 58 cases. Allergen-specific IgE for the food allergens and inhalant allergens in patient’s serum was determined using the AllergyScreen system (Mediwiss Analytic GmbH, Germany). Results: Out of 106 AR children, 88 (83.02%) were tested positive for food allergen-specific serum IgE (sIgG), 97 (91.51%) positive for inhalant allergen-specific sIgE. Among these children, 79 (74.53%) were positive for both food and inhalant allergens, 9 (8.49%) were positive only for food allergens, and 18 (16.98%) were negative for food allergens but positive for inhalant allergens. Out of 88 children positive for food allergens, 34 (32.08%) were positive for single food allergen, 54 (50.94%) were positive for multiple food allergens. The top 6 food allergens, in the order of their positivity rates, were milk (52.83%), eggs (30.19%), beef (26.42%), cashew (26.42%), lamb (12.26%) and crabs (10.38%). The food allergen-positive rate in the preschooler group was higher than that in the school children group (P<0.05). Conclusion: Majority of the children with allergic rhinitis are also positive for food allergens, suggesting that food allergens might be one of the main causes for pediatric allergic rhinitis.The present study was undertaken to ascertain the affinity of the amino acid D-Tryptophan (D-Trp) towards the particular receptors on the melanophores of a major carp Labeo rohita (Ham.). D-Trp, which is sweet in taste, in the dose range of 4.9 x 10 -16 M to 4.9 x 10 -4 M has induced a dose-dependent aggregation (MSI 3.72 ± 0.15 to 1.09 ± 0.02) in the isolated scale melanophores of the dorso-lateral region of this fish. The precise binding of the ligand D-Trp with its receptors is partially dependent, in eliciting its actions, on the release of neurotransmitters. The melanophores do not get desensitized under 90 min incubation within the agonist D-Trp. The general α adrenoceptors as well as the α 2 adrenoceptors are involved in the tastant (D-Trp) induced aggregation of the melanophores. D-Trp demonstrates that its aggregatory effects are mediated with the intervention of the β adrenoceptors. Inhibition of the D-Trp induced aggregatory effect has also been observed when the melanophores were pretreated with the antibiotic neomycin. The aggregating nature of D-Trp suggests that it could be binding with the receptors of aggregation causing ligands.

Clinical study on cytomegalovirus-associated haemophagocytic syndrome following allogeneic hemotoic stem cell transplantation

Aims: To investigate the distribution of food allergens in pediatric allergic rhinitis. Methods: 106 children diagnosed with allergic rhinitis were reviewed and divided into two age groups, including preschooler (2-5 years old) group, 48 cases; and school children group (6-13 years), 58 cases. Allergen-specific IgE for the food allergens and inhalant allergens in patient’s serum was determined using the AllergyScreen system (Mediwiss Analytic GmbH, Germany). Results: Out of 106 AR children, 88 (83.02%) were tested positive for food allergen-specific serum IgE (sIgG), 97 (91.51%) positive for inhalant allergen-specific sIgE. Among these children, 79 (74.53%) were positive for both food and inhalant allergens, 9 (8.49%) were positive only for food allergens, and 18 (16.98%) were negative for food allergens but positive for inhalant allergens. Out of 88 children positive for food allergens, 34 (32.08%) were positive for single food allergen, 54 (50.94%) were positive for multiple food allergens. The top 6 food allergens, in the order of their positivity rates, were milk (52.83%), eggs (30.19%), beef (26.42%), cashew (26.42%), lamb (12.26%) and crabs (10.38%). The food allergen-positive rate in the preschooler group was higher than that in the school children group (P<0.05). Conclusion: Majority of the children with allergic rhinitis are also positive for food allergens, suggesting that food allergens might be one of the main causes for pediatric allergic rhinitis.The present study was undertaken to ascertain the affinity of the amino acid D-Tryptophan (D-Trp) towards the particular receptors on the melanophores of a major carp Labeo rohita (Ham.). D-Trp, which is sweet in taste, in the dose range of 4.9 x 10 -16 M to 4.9 x 10 -4 M has induced a dose-dependent aggregation (MSI 3.72 ± 0.15 to 1.09 ± 0.02) in the isolated scale melanophores of the dorso-lateral region of this fish. The precise binding of the ligand D-Trp with its receptors is partially dependent, in eliciting its actions, on the release of neurotransmitters. The melanophores do not get desensitized under 90 min incubation within the agonist D-Trp. The general α adrenoceptors as well as the α 2 adrenoceptors are involved in the tastant (D-Trp) induced aggregation of the melanophores. D-Trp demonstrates that its aggregatory effects are mediated with the intervention of the β adrenoceptors. Inhibition of the D-Trp induced aggregatory effect has also been observed when the melanophores were pretreated with the antibiotic neomycin. The aggregating nature of D-Trp suggests that it could be binding with the receptors of aggregation causing ligands.

Albendazole Therapy for Coagulation Abnormality in Children with Eosinophilia

Hemorrhage may be associated with eosinophilia. Here, 2 pediatric cases of coagulation abnormality were reported. The 2 children presented ecchymoses and petechiae in the skin. Laboratory investigations revealed hypereosinophilia in the peripheral blood. Moreover, the activity of coagulation factor IX significantly decreased. The serum immunoglobulin G (IgG) antibody to cysticercus was positive in patient 1, and IgG antibodies to cysticercus and plerocercoid were positive in patient 2. These 2 patients received 2 courses of albendazole therapy, at 15 mg/kg/day in divided doses for 10 days for each course. They responded well to the therapy. This report indicates that patients with hypereosinophilia and bleeding abnormalities should undergo evaluation of coagulation pathways, including measurements of coagulation factors.