Analysis with antiidiotype antibody of a patient with chronic lymphocytic leukemia and a large cell lymphoma (Richter's syndrome)

A murine monoclonal antibody made against an idiotypic determinant (Id) of surface IgM/IgD lambda molecules on chronic lymphocytic leukemia (CLL) cells of a 71-year-old woman was used for clonal analysis by two- color immunofluorescence. The anti-Id antibody identified IgM+/IgD+/lambda+ B cells as the predominant cell type of her CLL clone. In addition, substantial proportions of the IgG and IgA B cells and most of the IgM plasma cells in her bone marrow and blood were Id+. Six years after diagnosis, the patient died of respiratory failure due to infiltration of lungs by malignant cells. Autopsy revealed a dramatic change in the tumor cell morphology. The lungs, hilar nodes, and liver were infiltrated by a diffuse large cell lymphoma admixed with the leukemic cells. By immunohistologic staining these anaplastic lymphoma cells were IgM+/IgD-/lambda+ B cells expressing the same Id noted earlier on the CLL cells. The immunoglobulin gene rearrangement pattern on Southern blot analysis was also the same in leukemic blood cells and in the tissues involved by the lymphoma. Thus, the combination of antiidiotype and immunoglobulin gene analyses in this patient with Richter's syndrome revealed that a CLL clone, seemingly "frozen" in differentiation, was actually undergoing isotype switching, differentiation into plasma cells, and evolution into a rapidly growing and fetal lymphoma.     

Kinetics of CD4 cells after discontinuation of antiretroviral therapy in patients with virological failure and a CD4 cell count greater than 500 cells/microl

After a median of 37 months on antiretroviral therapy, 16 patients were asked to discontinue treatment instead of changing it. After a median observation time of 10.5 months, most patients experienced a rapid and progressive decrease in their CD4 cell count, even without a high viral load rebound. This decline was unrelated to the CD4 cell count and HIV-RNA values at interruption, but was more profound in patients in whom the M184V mutation had disappeared after lamivudine discontinuation.     

Hemophagocytic syndrome in patients with acute myeloid leukemia undergoing intensive chemotherapy

Hemophagocytic lymphohistiocytosis is a condition of immune dysregulation characterized by severe organ damage induced by a hyperinflammatory response and uncontrolled T-cell and macrophage activation. Secondary hemophagocytic lymphohistiocytosis typically occurs in association with severe infections or malignancies. Patients with acute myeloid leukemia may be prone to develop hemophagocytic lymphohistiocytosis because of an impaired immune response and a high susceptibility to severe infections. In a series of 343 patients treated by intensive chemotherapy over a 5-year period in our center, we identified 32 patients (9.3%) with fever, very high ferritin levels, and marrow hemophagocytosis (i.e. patients with hemophagocytic lymphohistiocytosis). Compared to patients without hemophagocytic lymphohistiocytosis, these 32 patients had hepatomegaly, pulmonary or neurological symptoms, liver abnormalities, lower platelet count and higher levels of C-reactive protein as well as prolonged pancytopenia. A microbial etiology for the hemophagocytosis was documented in 24 patients: 14 bacterial infections, 9 Herpesviridae infections and 11 fungal infections. The treatment of hemophagocytic lymphohistiocytosis consisted of corticosteroids and/or intravenous immunoglobulins along with adapted antimicrobial therapy. Patients with hemophagocytic lymphohistiocytosis had a median overall survival of 14.9 months, which was significantly shorter than that of patients without hemophagocytic lymphohistiocytosis (22.1 months) (P=0.0016). Hemophagocytic lymphohistiocytosis was significantly associated with a higher rate of induction failure, mainly due to deaths in aplasia. Hemophagocytic lymphohistiocytosis can be diagnosed in up to 10% of patients with acute myeloid leukemia undergoing intensive chemotherapy and is associated with early mortality. Fever, very high ferritin levels and marrow hemophagocytosis represent the cornerstone of the diagnosis. Further biological studies are needed to better characterize and recognize this syndrome in patients with acute myeloid leukemia.     

Diagnostic role of radiolabelled choline PET or PET/CT in hepatocellular carcinoma: a systematic review and meta-analysis

The role of fluorine-18-fluorodeoxygluose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in hepatocellular carcinoma (HCC) has not been firmly established yet and its sensitivity has been reported to be in the range of 40–60 %. Because of this relatively low sensitivity alternative tracers have been proposed. The aim of our review is to analyse the literature data on the diagnostic role of ¹⁸F/¹¹C-choline PET/CT in the evaluation of HCC. A comprehensive computer literature search of PubMed/MEDLINE, Embase and Scopus databases was conducted to find relevant published articles about the role of whole-body ¹⁸F-choline or ¹¹C-choline PET or PET/CT in patients with HCC. Furthermore, a meta-analysis about the detection rate of this method in HCC was performed. Six articles were included in this systematic review and discussed. The meta-analysis of five out of six articles showed a DR of 84 % (95 % CI 79–89 %). The DR increased when poorly differentiated HCC was excluded from the analysis. Radiolabelled choline PET or PET/CT could be a valuable tool in detecting HCC and it is better than ¹⁸F-FDG PET/CT, especially in well to moderately differentiated lesions; on the other hand, poorly differentiated and higher-stage HCC could be better evaluated with ¹⁸F-FDG and dual tracer imaging should be considered and could be potentially useful to increase accuracy.     

The development of mouse zygotes after fusion with synchronous and asynchronous cytoplasm

Cytoplasts with diameters of 40–45, 50–55 and 70–75µm, derived from mouse oocytes at the germinal vesicle,metaphase II and zygote stages were incorporated into zygotesby electrofusion. Manipulated (n = 867) and culture-control(n = 1114) embryos were cultured in vitro and transferred topseudo-pregnant recipients at the blasto-cyst stage. When synchronouscytoplasts measuring 40–45 and 50–55 µm indiameter were incorporated into 138 and 86 zygotes respectively,only one embryo in each group (not significant) became arrestedat the 1-cell stage. A total of 124 (89.9 compared with 91.6%for controls) and 69 embryos (80%, P < 0.001 compared with91.6% for controls) reached the blastocyst stage respectively.In the first group, 66 out of 106 blastocysts implanted (62.2compared with 54.9% for controls; not significant), however,only 24 (22.6 compared with 40.2% for controls, P < 0.001)were viable in comparison with controls. There were four groupsof zygotes that received metaphase II cytoplasts. In the firstgroup, 200 zygotes were fused with 40–45 µm cytoplasts.The second group of 145 zygotes were fused with cytoplasts ofthe same size derived from aged oocytes. In the third and fourthgroups, 38 and 36 zygotes were fused with 50–55 and 70–75µm cytoplasts respectively. In the first two groups, noneof the embryos arrested at the 1-cell stage, but in the othergroups the rates were 15 out of 38 (39.5%) and 36 out of 36(100%) respectively. These zygotes remained arrested at thepronuclear stage and contained large inflated pronuclei. Theblastocyst formation rates were 183 out of 200 (91.5 comparedwith 91.6% for controls, not significant), 109 out of 145 (75.2%lower than controls, P < 0.05) and 14 out of 38 (39.5% lowerthan controls, P < 0.0001) respectively. In the first twogroups 109 and 25 blastocysts were transferred, of which 76(69.7%) and 15 (60.0%) implanted. This was higher than controlembryos (54.9%, P < 0.01) for the first group and similarto controls for the second group. In the first group, 60 embryos(55%) were viable on day 10 of transfer in comparison with controls(40.2%, P < 0.05) while in the second group, 11 embryos (44.0%,not significant) were viable on day 10 of transfer. Zygotesthat received germinal vesicle stage cytoplasts developed poorlyand the implantation rate was significantly reduced. The presentstudy confirms the importance of the ooplasmic domain in meioticmaturation and preimplantation development Our results suggestthat implantation may be enhanced by transfer of a small amountof metaphase II cytoplasm to the mouse embryo during the 1-cellstage; however, fusion of intact zygotes with cytoplasts >45µm appeared largely detrimental. The mechanisms responsiblefor these changes are yet unknown.     

The contribution of oxidative stress in apoptosis of human-cultured astroglial cells induced by supernatants of HIV-1-infected macrophages.

Apoptosis of neurons and astrocytes has been found in patients undergoing AIDS dementia complex. We demonstrated that supernatants from human primary macrophages (M/M) infected by HIV-1 lead human astroglial cells to oxidative stress, as shown by elevated levels of malondialdehyde, and then to apoptosis. Electron microscopy of astrocytes shortly incubated with HIV-1-infected M/M supernatants showed apoptotic blebbing, cytoplasmic loss, and chromatin condensation. Apoptosis was antagonized by pretreating astrocytes with the nonpeptidic superoxide dismutase (SOD) mimetic M40401 but not with anti-HIV-1 compounds, thus showing that apoptosis of astrocytes driven by HIV-1-infected M/M supernatants is mainly mediated by abnormal production of superoxide anions without relationship to HIV-1 replication in such cells. Overall results support the role of oxidative stress mediated by HIV-1-infected M/M as one of the leading causes of neurodegeneration in patients with HIV-1 and suggest the use of nonpeptidic SOD mimetics to counteract HIV-1-related neurological disorders.