Susumu Hagisawa

Docetaxel-induced apoptosis in the mitotic phase: electron microscopic and cytochemical studies of human leukemia cells

We induced apoptosis in cells of the human leukemia cell line HL-60 using an antitumor agent, docetaxel (Taxotere), and investigated apoptosis in various aspects using in situ end-labeling (ISEL) of DNA, DNA fragmentation assay, flow cytometry, and electron microscopy. Because it inhibits depolymerization of tubulin, docetaxel is thought to arrest the cell cycle at the mitotic stage and to exert an antitumor effect. In this study, accumulation of docetaxel-treated cells at the G2/M phase was detected using flow cytometry. On ISEL of DNA, DNA fragmentation was observed at the mitotic stage. On electron microscopy, the nuclei of apoptotic cells lost their nuclear membranes, as do cells at mitosis, demonstrating that the cells were arrested mainly at the M phase in the cell cycle.

Effect of Excess Estrogen on Breast and External Genitalia Development in Growth Hormone Deficiency

BACKGROUND The progress of sexual maturation and development in cases with growth hormone (GH) and insulin-like growth factor-I (IGF-I) deficiency is not well documented in females. CASE We observed breast and genitalia development in a 2-year-old girl with GH deficiency following neonatal asphyxia; this girl later developed central precocious puberty. Markedly pigmented stimulated areolas and nipples without an apparent breast mound, and non-enlarged labia minora in the external genitalia were observed as features of sexual maturation in the patient. The hormonal condition was characterized by increased circulating estradiol levels and extremely low IGF-I levels. SUMMARY AND CONCLUSION This case indicates that IGF-I is necessary for exerting the full effect of estrogen on the development of breasts and maturation of external genitalia.

Chronic active Epstein–Barr virus infection with mosquito allergy successfully treated with reduced‐intensity unrelated allogeneic bone marrow transplantation in a boy

Abstract:  EBV‐infected T‐/NK cells play an important role in the pathogenesis of mosquito allergy, and the prognosis of most patients with mosquito allergy is poor without proper treatment. We describe a 13‐yr‐old boy who had CAEBV with mosquito allergy and was successfully treated with BMT from an unrelated donor after reduced‐intensity preconditioning. Because combination chemotherapy failed to achieve CR, we performed unrelated BMT to reconstitute normal immunity and eradicate any residual EBV‐infected cells. To reduce complications after BMT, we selected a reduced‐intensity preconditioning regimen consisting of fludarabine, l‐phenylalanine mustard, and antithymocyte Ig instead of a conventional myeloablative preconditioning. Although grade II acute GVHD developed, it was successfully controlled with immunosuppressive therapy. After 27 months, the patient has been well without any signs of CAEBV, and the EBV DNA has been undetectable with real‐time PCR analysis. We conclude that RIST from the bone marrow of an unrelated donor is indicated for some patients who have CAEBV that is refractory to chemotherapy and who have no HLA‐matched related donors or cord blood as a source of stem cells.

JAK2V617F mutation-positive childhood essential thrombocythemia associated with cerebral venous sinus thrombosis.

Myeloproliferative diseases (MPDs) in childhood are quite rare. Although pediatric and adult MPDs exhibit similar hematologic findings, JAK2V617F mutations and clonality status of MPDs in the DNA of neutrophils are evaluated less frequently in children than in adults. Increased incidence of venous thrombosis at uncommon sites is associated with JAK2V617F mutation in MPDs and thrombotic complications are more common in essential thrombocythemia (ET). Here, we describe 6-year-old girl with clonal myelopoiesis and JAK2V617F-positive ET associated with cerebral venous sinus thrombosis. To our knowledge, this is the first report of pediatric monoclonal and JAK2V617F-positive ET with cerebral venous sinus thrombosis.

I-131-Metaiodobenzylguanidine therapy with allogeneic cord blood stem cell transplantation for recurrent neuroblastoma.

Iodine-131-metaiodiobenzylguanidine (131I-MIBG) therapy combined with allogeneic cord blood stem cell transplantation (SCT) was used to treat a 4-year-old girl with recurrent neuroblastoma. The patient experienced relapse 2 years after receiving first-line therapies, which included chemotherapy, surgical resection, irradiation, and autologous peripheral SCT. Although 131I-MIBG treatment did not achieve complete remission, the size of the tumor was reduced after treatment. Based on our findings, we suggest that 131I-MIBG treatment with myeloablative allogeneic SCT should be considered as first-line therapy for high-risk neuroblastoma patients when possible.

Viridans Streptococcal Bacteremia–Related Encephalopathy in Childhood with Malignancy

Viridans streptococcal bacteremia is a prognostic factor in pediatric patients with malignant disease accompanied by severe neutropenia. Here the authors describe 4 patients with viridans streptococcal bacteremia–related encephalopathy who showed serious complications, which included seizures and loss of consciousness. Therapy for relief of brain edema on seizures was started quickly, and included the administration of midazolam, dexamethasone, and mannitol with antimicrobial therapy. The treatment was successfully completed without sequelae. The authors registered 28 episodes of viridans streptococcal bacteremia in their hospital. The peak of serum C-reaction protein was higher in viridans streptococcal bacteremia patients with encephalopathy than in those without encephalopathy. The authors concluded that viridans streptococcal bacteremia can induce encephalopathy in pediatric patients with malignancy and that it is crucial to establish an accurate diagnosis and initiate therapy as soon as possible.

Fluctuations in C-reactive protein in a hepatoblastoma patient with thrombocytosis

We observed the changes in serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP) in a patient with hepatoblastoma exhibiting thrombocytosis. The concomitant changes of IL-6 and CRP concentrations after the initiation of chemotherapy, in the absence of infection, suggested that the IL-6, which is synthesized in hepatoblastoma cells and induces thrombocytosis, also stimulated CRP production in the present case. IL-6 is thought to play an important role in thrombocytosis in hepatoblastoma.