Inhibition of leukemic cell proliferation by one or more factors released from splenic BCL1 cells.

Irradiated peripheral blood lymphocytes from patients with chronic B-lymphocytic leukemia (B-CLL) have been shown to secrete a factor or factors that caused inhibition of malignant cell proliferation. In the present study, we used the murine B cell leukemia (BCL1) model system to examine the possible secretion of inhibitory factors from irradiated leukemic spleen cells. It was found that under culture conditions, irradiated spleen cells obtained from leukemic mice produce factors capable of suppressing BCL1 cell proliferation in vitro.

Doctoring III: innovations in education in the clinical years.

Despite recent major changes in the practice of medicine, there has been relatively little change in medical education, particularly in the clinical years. Important areas such as ethics, domestic violence, nutrition, preventive medicine, and clinical decision making have been neglected in the curriculum. However, in 1994 the UCLA School of Medicine began to implement Doctoring III, a multidisciplinary, centralized, longitudinal course that spans the third year of medical school.

Elevated inflammatory cytokine levels in bone marrow graft rejection.

Graft rejection and graft failure represent major obstacles in allogeneic bone marrow transplantation (BMT). Cytokines possibly play a central role in the inflammatory and allospecific components of allograft rejection. Therefore, we evaluated inflammatory cytokine levels following BMT in 12 consecutive patients with graft rejection (GR).

Ex vivo expansion of megakaryocyte precursors by preincubation of marrow allografts with interleukin-3 and granulocyte-macrophage colony-stimulating factor in vitro.

Protracted thrombocytopenia and bleeding remain serious complications in bone marrow transplantation (BMT). Major progress has been made in facilitating myeloid and erythroid engraftment, but little has been made in accelerating thrombopoiesis post-BMT. We report that in vitro preincubation of T cell-depleted BM allografts with a combination of interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (0.

Analysis of beta-globin mutations shows stable mixed chimerism in patients with thalassemia after bone marrow transplantation.

Beta-thalassemia major (TM) is caused by any of approximately 150 mutations within the beta-globin gene. To establish the degree of chimerism after bone marrow transplantation (BMT), we have performed molecular analysis of beta-globin mutations in 14 patients with TM over a period of 10 years. All patients underwent T cell-depleted allogeneic BMT from HLA-identical related donors, using either in vitro T-cell depletion with CAMPATH 1M and complement or in vivo depletion using CAMPATH 1G in the bone marrow collection bag.

Reactions of family medicine community preceptors to teaching medical students.

Background And Objectives: In 1993, the University of California, Los Angeles introduced an interdisciplinary course called ¿Doctoring¿ for all first-year medical students in which students visited family physicians' offices once a month for a total of four visits. The study's objectives were to ascertain preceptors' attitudes about having students in their offices and determine if this experience resulted in professional growth.

Methods: A survey was mailed to the 101 preceptors recruited to teach in the ¿Doctoring¿ course.

Recombinant human interleukin-6 accelerates in-vitro megakaryocytopoiesis and platelet recovery post autologous peripheral blood stem cell transplantation.

Prolonged thrombocytopenia complicated by bleeding episodes represent a major problem following autologous bone marrow transplantation (ABMT). Recombinant human interleukin-6 (rhIL-6) has been shown to be a maturation factor for both mouse and human megakaryocytes. We administered rhIL-6 to a 43 year old woman who developed marked resistant and prolonged thrombocytopenia with bleeding episodes following autologous peripheral blood stem cell transplantation (APBSCT).

Induction of tumor immunity by intact irradiated leukemic B cells (BCL1) bearing a tumor-associated cell-surface idiotype and the costimulatory B7 molecule.

The idioptypic (Id) determinant of immunoglobulin expressed on the cell surface of malignant B cells represents a prototypical tumor-associated antigen (TAA), which has been used in a purified soluble form for active immunization in experimental tumor models and human hematological malignancies. Using a spontaneous transplantable murine model of B cell leukemia/lymphoma (BCL1), we have demonstrated the expression of the B7 costimulatory molecules in addition to the previously described Id determinant and class II major histocompatibility antigens. Intact irradiated BCL1 cells bearing these distinct determinants induced long lasting antitumor immunity in naive syngeneic mice.

Role of interleukin-2 in human hematological malignancies.

Clinical studies with Interleukin-2 (IL-2) in human hematologic malignancies were initiated in the late 1980s. Based on clinical studies on various solid tumors, and laboratory research on hematopoietic cells, IL-2 was shown to be effective in 150 acute myeloid leukemia (AML) patients mainly for maintenance therapy in first complete remission, or with residual blast cells in the marrow. IL-2 has also been shown to be effective in remission induction in 10 patients with chronic myeloid leukemia (CML).

The role of antibodies to IL-2 receptor and Asialo GM1 on graft-versus-leukemia effects induced by bone marrow allografts in murine B cell leukemia.

The role of various cell subpopulations involved in the graft-versus-leukemia (GVL) effect induced by allogeneic bone marrow transplantation (BMT) was investigated in (BALB/c x C57BL/6)F1 (F1) recipients, inoculated with murine B cell leukemia (BCL1), by using monoclonal murine anti-IL-2 receptor antibodies or rabbit anti-Asialo GM1 antibodies directed predominantly against murine NK cells. F1 mice with BCL1 were irradiated and reconstituted with parental (C57BL/6) bone marrow cells (BMC) or a mixture of BMC and spleen cells and treated in vivo for 10 days with anti-IL-2 receptor antibody or anti-Asialo-GM1 antibody. Both treatments lessened the GVL effects induced by the allograft and resulted in development of leukemia relapse, as documented in vivo by adoptive transfer of 10(5) spleen cells obtained from treated mice into secondary syngeneic adoptive recipients.

Induction of tolerance to experimental anti-phospholipid syndrome (APS) by syngeneic bone marrow cell transplantation.

Previously, we have shown the ability to induce experimental autoimmune conditions (e.g. SLE, APLS, Wegener's granulomatosis) following active immunization with the pathogenic autoantibody emulsified in adjuvant.

Successful matched unrelated transplantation from a donor with idiopathic thrombocytopenic purpura (ITP).

The case of a 5 year old male is described who had acute myeloblastic leukaemia (AML M5) and was in third remission when he underwent an allogeneic T cell depleted bone marrow transplantation (BMT). The bone marrow was from an HLA matched unrelated donor (MUD) who suffered from chronic idiopathic thrombocytopenic purpura (ITP). In spite of this, the patient had rapid platelet engraftment post BMT (> 50 x 10(9) l-1 on day 20).

Ketotifen therapy in chronic graft-versus-host disease (cGVHD): effect on mast cells and fibroblasts.

Current treatment options for cGVHD are limited. Mast cells (MC) and fibroblasts have been shown to play a role in the murine model of cGVHD. Ketotifen is an anti-H-1 antihistamine with MC-stabilizing properties.

Immunomodulation of autoimmunity in MRL/lpr mice with syngeneic bone marrow transplantation (SBMT).

MRL-lpr/lpr mice spontaneously develop a severe autoimmune syndrome, characterized by massive generalized lymphadenopathy, arthritis, arteritis, dermatitis and immune complex-mediated glomerulonephritis. Bone marrow transplantation (BMT) from MHC-matched systemic lupus erythematosus (SLE)-resistant donors to susceptible recipients has proved effective in correcting autoimmune manifestations in autoimmune-prone mice. We investigated the effect of syngeneic BMT from MRL/lpr (donor) to immunocompromised MRL/lpr (recipient), after purging the bone marrow inoculum with MoAbs against mature T cells (anti-Thy 1.

Enhancement of GVL effect with rhIL-2 following BMT in a murine model for acute myeloid leukemia in SJL/J mice.

A murine model for acute myeloid leukemia (mAML) was used to study graft-vs.-leukemia (GVL) effects on residual leukemic cells across both major (MHC) and minor histocompatibility antigens (mHA) barriers. In addition, the therapeutic effect of recombinant human interleukin-2 (rhIL-2)-administered postsyngeneic and allogeneic bone marrow transplantation (BMT) was examined.

Successful immunization of autologous bone marrow transplantation recipients against hepatitis B virus by active vaccination.

Patients undergoing autologous bone marrow transplantation (BMT) are severely immunosuppressed. These patients are exposed to various infections agents due to delayed and efficient reconstitution of their immune system. Forty-eight patients with hemato-oncological malignancies were immunized against hepatitis B virus (HBV) following autologous BMT.

A longitudinal follow-up of salivary secretion in bone marrow transplant patients.

Salivary gland dysfunction is a common sequela of the bone marrow transplantation procedure. We determined the effect of different bone marrow transplantation protocols on parotid salivary flow rate. Salivary secretion was substantially reduced during conditioning of all the recipients.

The response of cord blood megakaryocyte progenitors to IL-3, IL-6 and aplastic canine serum varies with gestational age.

Fetal cord blood (CB) is rich in haemopoietic stem cells and progenitors. We studied the clonogenic, proliferative and maturational responses of megakaryocyte (MK) progenitors in CB, from different gestational ages, to various cytokines: IL-3, IL-6, IL-3 + IL-6, and aplastic canine serum (PICS-J), and compared their responses to those of progenitors in adult peripheral blood (PB) or bone marrow (BM). We found that 34-week gestation CB produced some spontaneous colonies 28 +/- 4.

Silicone gel implant explantation: reasons, results, and admonitions.

Managing the patient who requests removal of her silicone gel implants, either intact or ruptured, can be difficult because the treatment depends on the desires and perceptions of the individual patient, especially in the present absence of data concerning the possible long-term adverse consequences of a silicone gel implant, intact or ruptured. Over 12 months, 46 women underwent removal of 74 silicone gel implants placed for augmentation in 26 and reconstruction in 20. Reason for removal was fear of possible consequences of the silicone gel in 17 patients, aesthetic concerns related to encapsulation in 14, systemic symptoms in 8, rupture determined by mammography in 7, and fear of interference with mammography or clinical examination for breast cancer in 4.

Involvement of interleukin-2 in immunologic reconstitution following bone marrow transplantation in mice.

Allogeneic or autologous bone marrow transplantation (BMT) is a curative form of treatment for patients with a variety of hematologic disorders. Impaired immune reconstitution following BMT may seriously impede successful outcome. In this study, the immune function of spleen and thymus was investigated in mice exposed to myeloablative total-body irradiation followed by syngeneic BMT.

Prevention of diabetes mellitus in non-obese diabetic mice by Linomide, a novel immunomodulating drug.

Oral administration of the synthetic immunomodulating drug quinoline-3-carboxamide (Linomide) in the drinking water to 5-week-old female non-obese diabetic (NOD) mice resulted in complete protection from insulitis and maintenance of normal glucose tolerance for over 40 weeks (impaired glucose tolerance: treated n = 2 of 18; control n = 17 of 18, p < 0.0001). Delayed administration of the drug at 16 weeks resulted in slowing of the progression to diabetes when assessed at 42 weeks (treated with diabetes n = 7 of 25; control with diabetes 25 of 43, p < 0.