Antibody-induced modulation and intracellular transport of CD10 and CD19 antigens in human B-cell lines: an immunofluorescence and immunoelectron microscopy study

Antibody-induced antigenic modulation (AIAM) of CD10 and CD19 was studied on NALM-6, RAJI, and JOK-1 cell lines using fluorescence microscopy (FM), flow cytometry (FCM), and immunoelectron microscopy (IEM). Cross-linking with monoclonal antibodies (MoAbs) induced rapid redistribution of CD10 and CD19 on the cell surface (FM) followed by internalization involving uptake through plasmalemmal pits, transfer through endosomal compartment (receptor-mediated endocytosis), and, finally, delivery to lysosomes for degradation or exocytosis and recycling (IEM). Significant quantitative differences regarding modulation and intracellular processing were shown by FCM and IEM. Thus, 35%, 30%, and 25% of CD10 compared with 80%, 60%, and 40% of CD19 were internalized in NALM-6, RAJI, and JOK-1 cells, respectively. Also, the rate of intracellular transfer as well as externalization and recycling was more pronounced in the case of CD19 than of CD10 and in the NALM-6 and RAJI cells compared with the JOK-1 cells. These differences may possibly reflect the functional significance of CD10 and CD19 as well as the stage of differentiation of the malignant B cells. Although both antigens can be useful in MoAb-targeted immunotherapy, our findings suggest that anti-CD19 MoAbs would be preferable for delivery of cytotoxic agents to malignant B cells.     

A survey of current management of Benign Paroxysmal Positional Vertigo (BPPV) by physiotherapists’ interested in vestibular rehabilitation in the UK

ObjectivesBenign Paroxysmal Positional Vertigo (BPPV) is the most common cause of dizziness. Extensive research has identified the best assessment and treatment manoeuvres for each subtype of BPPV. Education in vestibular rehabilitation (VR) is inconsistent. It is unclear if the evidence has been adopted by UK physiotherapists in clinical practice and no research has investigated this specifically.DesignAn online survey with closed- and open-text answers.ParticipantsA purposive sample of physiotherapists interested in VR. A response rate of 67% (100/150) was obtained, from which 20 responses were excluded.ResultsParticipants had good evidence-based awareness in assessment (79/80, 99%) and treatment (72/80, 90%) of posterior BPPV. Horizontal BPPV assessment awareness was lower than treatment (37/80, 46% vs 60/80, 75%). Differential diagnosis was poor in subjective (20/80, 25%) and objective stages of assessment (34/80, 43%). Thirty six percent (29/80) were able to list ≥3 test precautions with all three nystagmus characteristics described by 29% (23/80). Eighty one percent (65/80) encourage activity restrictions post-treatment. Only 28% (22/80) were aware of practice guidelines or Cochrane reviews in BPPV.External courses were rated the top method for learning how to manage BPPV. Lack of peer support (26/77, 34%) was the main challenge faced whilst learning. Recommendations for improving BPPV education included more external courses (23/87, 26%) and competency guidelines (13/87, 15%).ConclusionsGood awareness of research evidence was observed in some aspects of BPPV management but many areas require development. Translation and implementation of evidence remains poor and suggests changes in education and knowledge dissemination are warranted.     

Persistence of host-type hematopoiesis after allogeneic bone marrow transplantation for leukemia is significantly related to the recipient's age and/or the conditioning regimen, but it is not associated with an increased risk of relapse

We investigated the chimerism pattern within flow-sorted peripheral blood- or bone marrow-derived cell populations after allogeneic bone marrow transplantation (BMT) for the treatment of leukemia in children. This study was performed to define the identity of persistent host-type cells, to identify prognostic variables for the persistence of host- type hematopoiesis, and to determine the prognostic significance of the chimerism pattern on the duration of the leukemia-free interval, the overall survival, and the leukemia-free survival. The patients received either HLA-identical non-T-cell-depleted (n = 46) or HLA nonidentical T- cell-depleted (n = 7) BMT. In the peripheral blood, the children showed either stable mixed chimerism (SMC; ie, persistent host-type hematopoiesis; n = 14), (transient) mixed T-lymphoid chimerism (MTLC; n = 9), or complete chimerism (CC; n = 30). In the bone marrow, only donor-type cells were found in children with either CC (n = 8) or MTLC (n = 2), and a mixture of donor- and recipient-type cells was found in children with SMC (n = 7). The persistence of host-type hematopoiesis (SMC) was significantly related to a lower age of the recipient, the type of conditioning regimen, a lower total body irradiation dose, T- cell depletion of the bone marrow graft, and the use of cyclosporine A for acute graft-versus-host disease prophylaxis. No significant differences were found between patients with (SMC) or without (CC/MTLC) persistent host-type hematopoiesis with respect to the duration of the leukemia-free interval, the overall survival, or the leukemia-free survival. We conclude that ablation of host-type hematopoiesis is not compulsory for long-term leukemia-free survival after allogeneic BMT for various hematologic malignancies.