Signal transduction through the CD19 receptor during discrete developmental stages of human B-cell ontogeny.

We present evidence that the CD19 receptor is functionally operative and transmits pleiotropic signals throughout the pro-B, pre-pre-B, pre-B, early B, and mature B cell stages of human B-cell ontogeny. The signaling ability of CD19 does not depend on the existence of a functional B-cell antigen receptor complex (ARC). In B-cell precursors (BCP) lacking a functional ARC, CD19 is physically and functionally associated with Src family protein tyrosine kinases (PTK).

Influence of heat on platelet biochemistry, structure, and function.

The present investigation has evaluated the influence of temperatures ranging from 37 degrees C to 45 degrees C for intervals of 30, 60, and 90 minutes on the biochemistry, morphology, and function of human platelets. Exposure to temperatures up to 43 degrees C for an hour did not significantly alter platelet morphology or physiologic response to aggregating agents. Samples of platelets heated at 43 degrees for 60 minutes lost their ability to aggregate in response to arachidonate, but sensitivity was restored by pretreatment with epinephrine.

Mucormycosis in the BMT population.

Mucormycosis is known to cause rhinocerebral and pulmonary disease in patients with diabetes, leukemia, and lymphoma. However, the characteristics and outcome of these infections have not been well described in the BMT population. In a 17-year consecutive series of BMT patients, 13 of 1500 patients (0.

Anti-human immunodeficiency virus type 1 activity of an anti-CD4 immunoconjugate containing pokeweed antiviral protein.

The ability of an alpha CD4-pokeweed antiviral protein (PAP) immunoconjugate to inhibit replication of human immunodeficiency virus type 1 (HIV-1) was evaluated in vitro with 22 clinical HIV-1 strains obtained from four seropositive asymptomatic individuals, three patients with AIDS-related complex, and four patients with AIDS. Fifteen isolates were from zidovudine-untreated individuals, whereas seven isolates were obtained after 24 to 104 weeks of therapy with zidovudine, alone or alternating with zalcitabine. Mean zidovudine 50% inhibitory concentrations (IC50s) were 126 nM (range, 1 to 607 nM) for isolates from zidovudine-untreated individuals and 2,498 nM (range, 14 to 6,497 nM) for strains from patients treated with antiretroviral agents.

Radiation damage repair capacity of primary clonogenic blasts in acute lymphoblastic leukemia.

The sublethal radiation damage repair capacity of primary clonogenic blasts [i.e., leukemic progenitor cells (LPC)] from 74 newly diagnosed acute lymphoblastic leukemia (ALL) patients was analyzed using LPC colony assays.

The spectrum of non-Candida fungal infections following bone marrow transplantation.

We evaluated a consecutive series of patients who underwent bone marrow transplantation (BMT) at a single institution between 1974 and 1989 for the occurrence of a non-Candida fungal infection in the first 180 days after BMT. Of the 1186 patients, 129 (11%) patients developed a total of 138 significant non-Candida fungal infections in this period. Eight patients had multiple distinct infections.

Intrinsic radiation resistance of primary clonogenic blasts from children with newly diagnosed B-cell precursor acute lymphoblastic leukemia.

The radiation sensitivity of primary clonogenic blasts from 44 children with newly diagnosed B-cell precursor acute lymphoblastic leukemia (ALL) was analyzed using leukemic progenitor cell (LPC) colony assays. The derived values for SF2 (surviving fraction at 200 cGy) and alpha (initial slope of radiation survival curves constructed according to the linear quadratic model) indicated a marked interpatient heterogeneity in intrinsic radiation sensitivity of LPC populations. The SF2 values ranged from 0.

Lack of CD24 antigen expression in B-lineage acute lymphoblastic leukemia is associated with intrinsic radiation resistance of primary clonogenic blasts.

The radiation sensitivity of primary clonogenic blasts from 27 children with immunologically classified CD2-CD5-CD7-CD19+slg- B-lineage acute lymphoblastic leukemia (ALL) was analyzed using leukemic progenitor cell (LPC) colony assays. Radiation survival curves of primary clonogenic blasts (ie, LPC) were constructed for each patient using computer programs for the single-hit multitarget as well as the linear quadratic models of cell survival. The D0 values ranged from 49 to 891 cGy (median, 239 cGy; mean +/- SE, 307 +/- 44 cGy) and the alpha values ranged from 0.

[Varicella: how and when to start antiviral treatment].

The Meeting "An Update on Chickenpox" (Florence, 19-3-1993) has contributed to verify, in the light of the most recent acquisitions, the new guidelines for a correct rationale in the diagnosis and therapy of chickenpox. The present availability of an effective specific antiviral therapy for chickenpox (acyclovir) leads to a careful selection of patients to be treated. The high incidence of chickenpox morbidity keeps long unaltered and, beyond the usually benign onset of the primary infection in the child, the severity of this pathology in particular subjects and situations at risk is to be certainly underlined.

Alternaria: a sinonasal pathogen of immunocompromised hosts.

Fungal infections remain a major cause of morbidity and mortality in immunocompromised patients. Although Candida and Aspergillus species are the most common fungal isolates, other less common fungal isolates such as Alternaria species are emerging as opportunistic pathogens associated with discrete clinical syndromes. We reviewed a 16-year consecutive series of bone marrow-transplant recipients and describe the presentation, treatment approach, and outcome of six cases of localized invasive sinonasal infection caused by Alternaria species in this series.

In vivo anti-leukemic efficacy of anti-CD7-pokeweed antiviral protein immunotoxin against human T-lineage acute lymphoblastic leukemia/lymphoma in mice with severe combined immunodeficiency.

Mice with severe combined immunodeficiency (SCID) were injected with 1 x 10(7) MOLT-3 human T-lineage acute lymphoblastic leukemia cells to provide a model for the evaluation of anti-CD7-pokeweed antiviral protein (PAP) immunotoxin directed against the human CD7 antigen. Of control SCID mice (treated with phosphate-buffered saline, PBS) challenged intravenously with 1 x 10(7) MOLT-3 cells, 5/5 died at 29 to 35 days after inoculation, with a median event-free survival of 33 days. Similarly, 6/6 anti-CD19-PAP treated control SCID mice died of MOLT-3 leukemia at a median of 36 days.

Combination chemotherapy in the treatment of follicular low-grade lymphoma.

The therapeutic approach to patients with follicular low-grade non-Hodgkin's lymphoma is controversial and has varied over a wide spectrum. A "watch and wait" approach in asymptomatic patients has been taken in some studies. In other series, single agent therapy with alkylating agents as cyclophosphamide or chlorambucil has been employed.

Natural history of atherosclerosis and hyperlipidemia in heterozygous WHHL (WHHL-Hh) rabbits. I. The effects of aging and gender on plasma lipids and lipoproteins.

Plasma lipid and lipoprotein levels are influenced by physiologic changes during the life span of mammalian organisms. In the present study, the effects of aging and gender on plasma lipids and lipoprotein cholesterol fractions in heterozygous Watanabe heritable hyperlipidemic (WHHL-Hh) rabbits were examined. For 3 years the rabbits were fed regular rabbit chow and were free from any experimental manipulation.

Natural history of atherosclerosis and hyperlipidemia in heterozygous WHHL (WHHL-Hh) rabbits. II. Morphologic evaluation of spontaneously occurring aortic and coronary lesions.

This study evaluated the morphologic appearance of spontaneous aortic and coronary atherosclerotic lesions in 21 of the 28, 3-year old, heterozygous Watanabe heritable hyperlipidemic (WHHL-Hh) rabbits whose lipid profiles were presented in part I of this report. In situ perfusion fixation of the arteries showed 100% of the aortas involved with one or another type of intimal lesion. In male rabbits (n = 13), the abdominal aortas had more severe fibrosis and more diffuse intima thickening than the thoracic aortas, (p < 0.

Current management of varicella zoster virus infections.

A series of randomized, placebo-controlled, double-blind clinical trials conducted from 1980 to the present provide the basis for appropriate management of varicella-zoster virus (VZV) infections. Placebo recipients in these studies have also provided valuable natural history data on the clinical course of VZV infections. The protocols in toto have shown acyclovir (ACV) to be safe and effective for treatment of nearly all forms of acute VZV infection.

Allograft and autograft purging using immunotoxins in clinical bone marrow transplantation for hematologic malignancies.

Bone marrow manipulation is an essential procedure when bone marrow transplantation (BMT) is used to improve the chances of survival among high risk patients with hematologic malignancies. Ex vivo purging of donor T cells effectively prevents a fatal reaction known as graft-versus-host disease in allogeneic BMT. Ex vivo purging of residual leukemia cells from autologous marrow can virtually eliminate the risk of autograft contamination.

Detergent-resistant cytoskeleton of the surface-activated platelet differs from the suspension-activated platelet cytoskeleton.

This study contrasts the protein composition of the detergent-resistant cytoskeleton of platelets fully spread on glass with the cytoskeletal composition of resting platelets and platelets aggregated in suspension with thrombin. Complete Triton X-100-insoluble cytoskeletons were isolated from spread, resting, and suspension-activated platelets in the presence of protease inhibitors, solubilized in sodium dodecyl sulfate/EDTA and analyzed on reduced, one-dimensional polyacrylamide gels. The protein composition of the cytoskeletons differed both qualitatively and quantitatively.

Developmental hierarchy during early human B-cell ontogeny after autologous bone marrow transplantation using autografts depleted of CD19+ B-cell precursors by an anti-CD19 pan-B-cell immunotoxin containing pokeweed antiviral protein.

Sequential immunophenotypes of bone marrow (BM) and peripheral blood (PBL) lymphoid cells from 15 B-lineage acute lymphoblastic leukemia (ALL) patients who underwent autologous bone marrow transplantation (BMT) during complete remission were determined by dual-color immunofluorescence and multiparameter flow cytometry. Autografts were depleted of CD19+ B-cell precursors by an immunochemopurging protocol that combines B43-PAP, a potent anti-CD19 immunotoxin, and the cyclophosphamide congener 4-hydroperoxycyclophosphamide (4-HC). A marked interpatient variation was observed in the appearance and expansion of B-cell precursors repopulating the posttransplant marrow.

Effective immunochemotherapy of CALLA+C mu+ human pre-B acute lymphoblastic leukemia in mice with severe combined immunodeficiency using B43 (anti-CD19) pokeweed antiviral protein immunotoxin plus cyclophosphamide.

A highly aggressive human CALLA+C mu+ pre-B acute lymphoblastic leukemia (ALL) cell line (NALM-6-UM1) causes disseminated and invariably fatal leukemia in CB.17 mice with severe combined immunodeficiency (SCID). We used this SCID mouse model of human pre-B ALL to evaluate and compare, in a total of 434 SCID mice, the antileukemic efficacy of B43 (anti-CD19)-pokeweed antiviral protein (PAP) immunotoxin and cyclophosphamide (CPA) as individual reagents and as combined immunochemotherapeutic regimens.

In vivo efficacy of B43 (anti-CD19)-pokeweed antiviral protein immunotoxin against BCL-1 murine B-cell leukemia.

We show that a highly aggressive subclone of murine BCL-1 B-lineage leukemia expresses a single 2.4-kb transcript hybridizing to the human CD19 cDNA probe and reacts strongly with the anti-human CD19 monoclonal antibodies (MoAb) B43, B4, Leu-12, and J3-119. In contrast to their strong reactivity with anti-human CD19 MoAb, BCL-1 cells show no reactivity with MoAb directed against human CD22, CD72, HLA-DR, IgD, or IgM.

In vivo efficacy of B43 (anti-CD19)-pokeweed antiviral protein immunotoxin against human pre-B cell acute lymphoblastic leukemia in mice with severe combined immunodeficiency.

A highly aggressive subclone of the human CALLA+C mu+ pre-B acute lymphoblastic leukemia (ALL) cell line NALM-6 (designated NALM-6-UM1) caused disseminated and fatal leukemia in CB.17 mice with severe combined immunodeficiency (SCID). An intravenous challenge with 1 x 10(6) (NALM-6-UM1 cells caused 15 of 27 (56%) SCID mice to become paraplegic at 31 +/- 2 days (median = 33 days) and 27 of 27 (100%) mice to die of disseminated leukemia at 38 +/- 1 days (median = 39 days).

Treatment of BCL-1 murine B-cell leukemia with recombinant cytokines. Comparative analysis of the anti-leukemic potential of interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF alpha), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), and their combination.

Murine BCL-1 B-cell leukemia provides a model of disseminated human B-lineage acute lymphoblastic leukemia (ALL) and non-Hodgkins lymphoma (NHL). This model was used to evaluate and compare the anti-leukemic efficacy of recombinant cytokines rIL-1 beta, rIL-2, rIL-6, rTNF alpha, rG-CSF, rGM-CSF and their combinations. Of these 6 cytokines tested, rG-CSF, rIL-1 beta, rIL-2, and rTNF alpha exerted a marked anti-leukemia/lymphoma activity, as reflected by significantly improved survival of treated mice after inoculation of BCL-1 cells.