Mantle cell lymphoma disguised as marginal zone lymphoma

We report a case of mantle cell lymphoma histologically indistinguishable from marginal zone lymphoma. An 83-year-old man presented with a 9.0-cm, slowly enlarging axillary mass. Microscopically, the neoplastic process was largely interfollicular, surrounding residual follicular centers, some of which had discernible small lymphocyte mantles. Overall, the morphologic pattern was highly suggestive of marginal zone lymphoma. However, flow cytometric and immunohistochemical results, including cyclin D1 positivity, revealed an immunophenotype that fit with mantle cell lymphoma. The differential diagnosis of mantle cell lymphoma is broad, and it is well known that mantle cell lymphoma can assume a number of histologic appearances, including, infrequently, that of more indolent B-cell non-Hodgkin lymphomas. Although not pathognomonic, cyclin D1 positivity is highly specific for mantle cell lymphoma and is key in distinguishing these clinically dissimilar malignant lymphomas. In recent years, detection of cyclin D1 has expanded the recognizable histologic spectrum of mantle cell lymphoma.     

Expression of HPCA-1 and HLA-DR antigens on growth factor- and stroma-dependent colony forming cells

The expression of HLA-DR and HPCA-1 antigens (recognized by the L243 and BI.3C5 antibodies respectively) on adult human bone marrow cells was examined by fluorescence activated cell sorting and colony assays. Nearly all the (day 14) lineage restricted and multipotential colony forming cells analysed in methylcellulose cultures in the presence of added growth factors express HLA-DR and HPCA-1 determinants. Two colour cell sorting reveals that the lineage restricted HLA-DR positive progenitors express variable levels of BI.3C5 positivity whereas most of the multipotential progenitors, the multi-CFC or CFU-GEMM, are highly BI.3C5 positive. The isolated HLA-DR and BI.3C5 positive populations also contain haemopoietic precursors which adhere to and form colonies on pre-formed stromal layers. Thus, haemopoietic progenitors assayed in both types of culture system can be analysed and enriched by simultaneous two-colour sorting using anti-HLA-DR and BI.3C5 monoclonal antibodies. Similarities in the antigenic phenotype of such cells, however, precludes the use of these reagents for segregating growth factor-dependent from stroma-dependent progenitors.     

Purification of haemopoietic progenitor cells from patients with chronic granulocytic leukaemia using Percoll density gradients and elutriation

Purification of haemopoietic progenitor cells from chronic granulocytic leukaemia buffy coat preparations requires a multistep approach using complementary cell separation techniques. In this study Percoll density gradient centrifugation and centrifugal elutriation were used to isolate large numbers of immature progenitor cells. Percoll density gradients were valuable as a first separation step: CFU-GM and CFU-GEMM could be enriched 75-fold in a light density fraction of d less than 1.056 g/ml and the technique could be adapted to cope with more than 10(10) buffy coat leucocytes. Progenitors cells were concentrated 3-fold by elutriation used as single method to separate buffy coat cells or when used to purify further light density Percoll fractions. When Percoll gradients and elutriation were used sequentially, undifferentiated mononuclear cells were enriched to more than 90% purity and between 5% and 40% of these cells formed CFU-GM or BFU-E colonies consisting of more than 40 cells. The enriched fractions were further characterized with monoclonal antibodies. The density and elutriation profiles of these colony forming cells resembled corresponding profiles of cells that reacted with the monoclonal antibody BI-3C5, which recognizes an antigen on primitive haemopoietic progenitor cells. Physical separation methods are a valuable first stage in the attempt to procure relatively pure myeloid progenitor cell populations, whose characteristics can then be further studied at a cellular or molecular level.     

A "public" T-helper epitope of the E7 transforming protein of human papillomavirus 16 provides cognate help for several E7 B-cell epitopes from cervical cancer-associated human papillomavirus genotypes.

We have identified a major T-cell epitope, amino acids 48-54 (DRAHYNI, in one-letter code) in the E7 open reading frame protein of human papillomavirus (HPV) type 16. Lymph node cells from mice immunized with synthetic peptides containing DRAHYNI proliferated and produced interleukin when challenged in vitro with peptide or whole HPV-16 E7 fusion protein. The T epitope was recognized in association with all five major histocompatibility complex class II I-A and I-E alleles tested. Synthetic peptides consisting of DRAHYNI linked to major B-cell epitopes on the E7 molecule formed immunogens capable of eliciting strong antibody responses to HPV-16 E7. The T epitope could provide help for the production of antibody to several B epitopes simultaneously, including a B epitope of HPV-18 E7 protein. Mice immunized with a peptide containing DRAHYNI and B epitope and, at a later date, infected with recombinant vaccinia E7 virus, displayed secondary antibody responses to E7. Because E7 has a role in cell transformation and is the most abundant viral protein in HPV-associated neoplastic cervical epithelial cells, the data have implications for vaccine strategies.     

Peripheral tolerance to human papillomavirus E7 oncoprotein occurs by cross-tolerization, is largely Th-2-independent, and is broken by dendritic cell immunization

The E7 oncoprotein of human papillomavirus 16 functions as a tumor-specific antigen in transformed epithelial cells of the uterine cervix to which immunotherapeutic strategies aimed at CTL induction may be directed. We previously have shown in mice transgenic for the E7 gene driven off an epithelial specific (keratin-14) promoter, that expression of E7 protein in peripheral epithelium is sufficient to tolerize E7-directed CTL precursors (pCTL; Doan et al, J. Virol., 73: 6166-1670, 1999). Here we show that E7 is presented to T cells for tolerization by cells of bone marrow origin ("cross-tolerization"). We demonstrate that tolerization of E7-directed pCTLs occurs within 2 weeks of exposure to E7 in epithelium. It is maintained in the near absence of CD4+ cells and in the absence of the thymus, and is independent of a coexisting E7-directed Th2-type antibody response. Tolerance was broken by immunization with E7 CTL epitope-pulsed dendritic cells. These findings have implications for immunotherapy of patients with human papillomavirus 16-associated cervical carcinoma, whose immune systems may have experienced long-term exposure to E7-expressing epithelial cells.     

Caring for carers of people with stroke: developing a complex intervention following the Medical Research Council framework

OBJECTIVE: To develop an intervention, using the first three phases of the Medical Research Council (MRC) framework for complex interventions, to facilitate coping skills in new carers of stroke patients. METHODS: In the preclinical (theoretical) phase, a theoretically based framework for a small group course for carers of people with stroke was developed. The intervention was grounded in a cognitive behavioural model and included carers' needs identified from a literature review. Phase I (modelling phase) comprised a qualitative study involving one-to-one semi-structured interviews with a purposive sample of informal carers of people with stroke. Following this, the intervention was modified. In phase II (exploratory phase), the modified intervention was delivered by a clinical psychologist and stroke nurse practitioner to five carers. Following postcourse interviews the course was further refined and delivered to seven new carers who subsequently completed a satisfaction questionnaire. RESULTS: Carers' needs identified from the literature included information provision; managing emotions; social support; health maintenance; and practical problem solving. Consultation with existing carers confirmed these as important issues with a strong emphasis on finding niches of control in life, becoming an expert carer, and dealing with emotional upheaval. Participants reported feeling more optimistic and empowered subsequent to the course. CONCLUSIONS: The MRC framework provided a useful methodology for the development of a complex intervention. The course aimed to assist carers to regain control over aspects of their lives and manage their emotions. It was feasible to run and acceptable to carers; however a randomized controlled trial (RCT) is required to evaluate its effectiveness.     

Purging of T-lymphocytes with magnetic affinity colloid

There is a well-documented correlation between the number of T-lymphocytes in the bone marrow graft and subsequent development of acute graft-versus-host disease after allogeneic bone marrow transplantation. The incidence of acute graft-versus-host disease may be decreased with elimination of mature T-lymphocytes from the bone marrow graft. We have developed an immunomagnetic separation procedure using an avidin-based magnetic affinity cobalt colloid. Bone marrow cells were incubated with a combination of CD2, CD3, CD4, and CD8 monoclonal antibodies. The cells were washed and then incubated with the biotinylated, affinity-purified IgG fraction of goat anti-mouse immunoglobulins followed by an avidin-based magnetic affinity colloid. The cells were then run through a high-magnetic gradient separation column utilizing an external samarium cobalt magnet. The number of residual T-lymphocytes was assessed by limiting dilution analysis of clonogenic T-lymphocytes. This procedure produces an approximately 1.7-log reduction of antibody-reactive cells with 45% recovery of hematopoietic progenitors (granulocyte-macrophage colony-forming cells, GM-CFC). This causes a reduction of T-lymphocytes in the bone marrow graft to approximately 5 x 10(5) cells/kg body weight.     

“I Felt Like a New Person.” The Effects of Mindfulness Meditation on Older Adults With Chronic Pain: Qualitative Narrative Analysis of Diary Entries

To identify the effects of mindfulness meditation on older adults with chronic low back pain (CLBP), we conducted a qualitative study based on grounded theory and used content analysis of diary entries from older adults who had participated in a clinical trial of an 8-week mindfulness meditation program. Participants were 27 adults ≥65 years of age with CLBP of at least moderate severity and of at least 3 months duration. We found several themes reflecting the beneficial effects of mindfulness meditation on pain, attention, sleep, and achieving well-being. Various methods of pain reduction were used, including distraction, increased body awareness leading to behavior change, better pain coping, and direct pain reduction through meditation. Participants described improved attention skills. A number of participants reported improved sleep latency as well as quality of sleep. Participants described achieving well-being during and after a meditation session that had immediate effects on mood elevation but also long-term global effects on improved quality of life. Several themes were identified related to pain reduction, improved attention, improved sleep, and achieving well-being resulting from mindfulness meditation that suggest it has promising potential as a nonpharmacologic treatment of chronic pain for older adults.

Perspective

Community-dwelling older adults with chronic low back pain experience numerous benefits from mindfulness meditation including less pain, improved attention, better sleep, enhanced well-being, and improved quality of life. Additional research is needed to determine how mindfulness meditation works and how it might help with other chronic illnesses.     

Peripheral blood stem cell transplants for multiple myeloma: identification of favorable variables for rapid engraftment in 225 patients

Transfusion of autologous peripheral blood stem cells (PBSCs) of good quality ensures fast hematopoietic engraftment after myeloablative therapy with a decrease in procedure-related morbidity and mortality. We have analyzed variables influencing the kinetics of engraftment, and therefore reflecting the quality of PBSC collections, in 225 patients with newly diagnosed or refractory multiple myeloma (MM) who received an autotransplant in support of high dose melphalan (200 mg/m2); 132 of these patients also completed a second transplant. All PBSCs were collected before the first transplant after high-dose cyclophosphamide (6 g/m2) and hematopoietic growth factors, mainly granulocyte- macrophage colony-stimulating factor. PBSCs were administered either alone (91 patients) or with bone marrow (134 patients). A highly significant correlation was observed between the number of CD34+ cells per kilogram infused and prompt recovery of both granulocytes (P = .0001) and platelets (P = .0001). After correction for the proportion of patients with > or = 2 x 10(6)/kg CD34 PBSCs infused and with < or = 12 months of prior therapy, no difference in engraftment kinetics was seen between patients receiving PBSCs only and those also receiving bone marrow. Exposure to chemotherapy, even to < or = 6 months of alkylating agents, significantly delayed hematopoietic recovery posttransplantation. The threshold dose of CD34 cells necessary for prompt engraftment was > or = 2.0 x 10(6)/kg for patients with < or = 24 months of chemotherapy before the first transplant, whereas greater than 5 x 10(6)/kg CD34 cells were required to assure rapid recovery also in those with longer exposure. Such quantities, easily collected in the large majority of patients with shorter exposure (91%), were obtained in only 28% of patients with more than 24 months of prior chemotherapy. Rapid platelet recovery within a narrow range of time (before day 14) was almost invariably seen (94%) when greater than 5 x 10(6)/kg CD34 cells were infused, irrespective of the duration of prior therapy, whereas the range widened progressively when less CD34 cells were infused. In the absence of CD34 measurements, fast recovery of platelets to greater than 50 x 10(9)/L within 14 days after high-dose cyclophosphamide and < or = 12 months of prior chemotherapy were the best predictors of early engraftment. Prudent use of stem cell-damaging agents, such as melphalan and nitrosoureas, is recommended in MM patients who might be candidates for autotransplantation. Alternatively, PBSCs should be collected early after diagnosis.