The farnesyl transferase inhibitor, tipifarnib, is a potent inhibitor of the MDR1 gene product, P-glycoprotein, and demonstrates significant cytotoxic synergism against human leukemia cell lines.

Farnesyl transferase inhibitors (FTIs) target signal-transduction pathways responsible for the proliferation and survival of hematologic malignancies, including acute myelogenous leukemias (AML). Lonafarnib has been shown to be a potent inhibitor of Pgp-mediated drug efflux. On the basis of these findings, we examined the Pgp-inhibitory properties of tipifarnib and assessed its activity when combined with anthracyclines.

Absence of FTL3 mutations in patients with JAK2V617F mutation negative essential thrombocythemia.

A common point mutation in the JAK2 tyrosine kinase leads to constitutive hematopoietic growth factor receptor signaling and was recently described in many patients with myeloproliferative disorders (MPDs). However, this JAK2 mutation is present in only a subset (35-50%) of patients with essential thrombocythemia (ET). Thus, the proliferative signals responsible for MPDs in the absence of JAK2 mutations remain largely unknown.

Production of autoantibodies associated with polyclonal activation in Yersinia enterocolitica O: 8-infected mice.

Polyclonal lymphocyte stimulation is one of the immunomodulatory mechanisms induced by arthritogenic pathogens. In this study we examined the polyclonal activation potential of a virulent strain of Y. enterocolitica serotype O: 8 (WA 2707(+)) and its plasmidless isogenic pair (WA 2707(-)).

Influence of Yersinia pseudotuberculosis outer proteins (Yops) on interleukin-12, tumor necrosis factor alpha and nitric oxide production by peritoneal macrophages.

An essential key to pathogenicity in Yersinia is the presence of a 70 kb plasmid (pYV) which encodes a type-III secretion system and several virulence outer proteins whose main function is to enable the bacteria to survive in the host. Thus, a specific immune response is needed in which cytokines are engaged. The aim of this study was to assess the influence of Yersinia outer proteins (Yops) released by Yersinia pseudotuberculosis on the production of the proinflammatory cytokines, interleukin-12 (IL-12), and tumor necrosis factor alpha (TNF-alpha), and nitric oxide (NO) by murine peritoneal macrophages.

Yersinia enterocolitica O:3 isolated from patients with or without reactive arthritis induces polyclonal activation of B cells and autoantibody production in vivo.

The mechanisms by which arthritis-provoking pathogens such as Yersinia enterocolitica interact with the human immune system to produce inflammatory synovitis are not well known. One of the immunomodulating mechanisms used against these pathogens is the polyclonal activation of lymphocytes. In this study, we investigated the extent of the B-lymphocyte activation induced in mice by a strain of Y.

Transfusion-related acute lung injury (TRALI) following platelet transfusion in a patient receiving high-dose interleukin-2 for treatment of metastatic renal cell carcinoma.

Transfusion-related acute lung injury (TRALI) is an uncommon life-threatening complication of hemotherapy. It is hypothesized to be the result of two independent insults: the first related to the clinical status of the patient and the second to the infusion of biologic response modifiers within blood components. We present a case of TRALI in a patient who received high-dose Interleukin-2 (IL-2) as treatment for metastatic renal cell carcinoma, where IL-2 is speculated to have been the first insult and transfusion of platelet concentrate the second.

Nonmyeloablative allogeneic hematopoietic stem cell transplantation for congenital sideroblastic anemia.

Congenital sideroblastic anemia (CSA) is a dyserythropoietic disorder that leads to transfusion dependency and subsequent iron overload. Nonmyeloablative allogeneic hematopoietic stem cell transplantation (NST) was performed for a patient with CSA, who had contraindications to conventional allografting. Conditioning was fludarabine, low-dose total body irradiation and antithymocyte globulin, followed by peripheral blood stem cell transplant.

Magical beliefs and rituals in young children.

Thirty-one children were administered a structured interview that assessed their beliefs about magic, tricks and wishes. Children were also presented with demonstrations of magic tricks/illusions, and asked to offer explanations as to how they worked. Parents completed the Childhood Routines Inventory (CRI), a 19-item parent report measure that assesses children's rituals, habits and sensory-perceptual experiences that we have termed "compulsive-like" behavior.

Cavernous sinus thrombosis caused by zygomycosis after unrelated bone marrow transplantation.

Invasive zygomycosis is a devastating fungal infection occurring as an opportunistic infection after bone marrow transplantation (BMT). Sinusitis can lead to fungal infection in immunosuppressed patients, and cavernous sinus thrombosis, an uncommon condition in immunocompetent patients, typically follows an infection involving the medial third of the face, nose, or paranasal sinuses. Patients undergoing unrelated-donor BMT (UD-BMT) are prone to develop life-threatening infections because of poor recovery of cellular immunity.

Intracranial hemorrhage following bone marrow transplantation: an autopsy study of 58 patients.

Autopsy files of 180 patients were reviewed, who died after BMT between July 1987 and June 1998 and 58 (32.2%) cases, who had experienced intracranial hemorrhage (ICH) were selected. Age, sex, underlying disease, preparatory regimens, immunoprophylaxis, chronic and acute GVHD, survival of the patients and localization and size of hemorrhages were evaluated.

Second bone marrow transplantation for severe aplastic anemia: analysis of 34 cases.

Severe aplastic anemia (sAA) is a bone marrow failure disorder which is mostly a consequence of immunologically mediated stem cell destruction. Allogeneic bone marrow transplantation (BMT) from a compatible donor provides long-term survival in 60 to 80% of sAA patients. However, graft rejection still remains a major problem, and a second allograft is an alternative for these patients.

Disseminated toxoplasmosis after bone marrow transplantation: report of 9 cases.

Toxoplasma infection following bone marrow transplantation (BMT) is infrequently reported. We report 9 cases of disseminated Toxoplasma gondii infection in BMT recipients documented during an 11-year period at our institution. The incidence of T.

Kaposi's sarcoma following allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia.

Unlike solid organ transplantation, Kaposi's sarcoma (KS) occurs rarely following hematopoietic stem cell transplantation (HSCT). In fact, only 5 cases of KS have been reported after allogeneic or autologous HSCT. The usual treatment combines a substantial decrease in, or elimination of, immunosuppressive therapy along with local measures such as surgical excision, cryotherapy or radiation therapy.

Unusual presentation of "extracavitary" primary effusion lymphoma in previously unknown HIV disease.

Human herpes virus, type 8, also called Kaposi's sarcoma-associated virus, is associated with primary effusion lymphoma, an uncommon and unusual subset of acquired immunodeficiency syndrome-related lymphomas mostly confined to body cavities, which primarily affects human immunodeficiency virus-positive men. We report the case of a 40-year-old male with primary effusion lymphoma that presented initially with generalized lymphadenopathy and hepatosplenomegaly, followed by pericardial effusion and cardiac tamponade, in a previously undiagnosed human immunodeficiency virus patient. Cytomorphological studies disclosed a large-cell lymphoma with a population of cells demonstrating intermediate CD45 expression and partial coexpression of CD20 and CD23 markers, as well as universal expression of HLA-DR, CD71, CD38, and CD-30.

Central nervous system infections following bone marrow transplantation: an autopsy report of 27 cases.

The authors retrospectively assess the autopsy findings of central nervous system (CNS) infections in marrow transplant recipients. From July 1987 to June 1998, 845 patients at our institution were submitted to bone marrow transplantation (BMT). The CNS of 180 patients was studied through autopsy and these patients had their medical records reviewed.

Neuropathological findings after bone marrow transplantation: an autopsy study of 180 cases.

We prospectively evaluated the neuropathological complications of 180 patients who underwent autopsy studies following bone marrow transplantation (BMT) (177 allogeneic, three autologous). The most frequent underlying disorders included severe aplastic anemia (n = 55), chronic myelogenous leukemia (n = 53), acute myelogenous leukemia (n = 24) and Fanconi anemia (n = 16). There were 114 males and 66 females.