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Biomedical subjects

E Naparstek

Publications and source records attributed to E Naparstek.

At least 109 records · Page 6Linked to original sources
PubMed1988

Prevention of herpes simplex virus (HSV) infection in recipients of HLA-matched T-lymphocyte-depleted bone marrow allografts.

The occurrence of HSV infection and the effect of prophylaxis with oral acyclovir were evaluated prospectively in 34 consecutive patients undergoing bone marrow transplantation (BMT). All allogeneic BMT procedures involved T-lymphocyte depletion for prevention of graft-vs.-host disease (GVHD). Five HSV-seronegative patients did not receive acyclovir, and they did not develop HSV infection. Oral acyclovir was administered to 15 HSV-seropositive BMT recipients; 14 untreated HSV-seropositive BMT recipients served as a control group. The adult dose of acyclovir was 400 mg three times a day on Days -6 to +14 and 200 mg three times a day on Days +15 to +90. Children received 500 mg/m2 per day divided into three equal doses on Days -6 to +14 and 250 mg/m2 per day again divided into three on Days +15 to +90. In the group on prophylaxis, only one developed HSV infection during the time prior to engraftment. In the reference group, 12 of 14 (85.7%) developed oral HSV infection within 0 to 16 days (median 11 days) after the transplantation. Time for engraftment (duration of neutropenia) was shorter in patients receiving acyclovir. After engraftment, HSV infection was not observed during administration or following discontinuation of acyclovir on Day 90, but occurred in three patients in whom acyclovir was discontinued on Days 25, 35 and 40 after BMT. In the untreated group, two patients had recurrence of HSV infection on Days 40 to 60, and one had two infectious episodes. GVHD occurred in only two recipients, neither of whom had HSV infection. We conclude that the incidence of HSV infection during the period until engraftment in recipients of T-lymphocyte-depleted BMT is high, similar to that reported by others in recipients of whole BMT. Relatively low-dose oral acyclovir administered for 90 days can effectively prevent HSV infections in previously HSV-seropositive BMT recipients and may also shorten the period until engraftment.

Acyclovir↗
PubMed1987

Hematopoietic effects of continuous intravenous infusion of mice with growth factors produced by the WEHI-3 cell line.

A method for continuous intravenous infusion of unanesthetized adult C3H/HeJ or Wx/Wv anemic mice was designed using cage immobilization and a tail vein catheter connected to a model 940 Harvard infusion pump. Infusates included: WEHI-3 cell line dialyzed, 5 times concentrated conditioned medium containing multi-colony-stimulating factor (C-SF) interleukin 3 (IL-3); purified murine IL-3; bacterial endotoxin; serum-free medium, or normal saline. Mice were monitored at days 5-7 after infusion for complete peripheral blood counts and production of granulocytes in vitro by explanted marrow in long-term bone marrow cultures. We observed a stimulatory effect of WEHI-3 conditioned medium infusion that was not attributable to endotoxin and produced significant increases in peripheral blood WBC count and neutrophils, colony-forming units in spleen and numbers of granulocyte/macrophage colony-forming unit culture responsive to both C-SF-1 (L cell C-SF) and multi-C-SF in vitro. This infusion method should prove valuable for test of the in vivo effects of purified growth factors and molecularly cloned hematopoietins.

Animals↗
PubMed1987

Interaction between x-irradiated plateau-phase bone marrow stromal cell lines and co-cultivated factor-dependent cell lines leading to leukemogenesis in vitro.

Plateau-phase mouse clonal bone marrow stromal cell lines D2XRII and C3H cl 11 produce decreasing levels of M-CSF (CSF-1), a specific macrophage progenitor cell humoral regulator, following X-irradiation in vitro. The decrease did not go below 40% of control levels, even after irradiation doses of 50,000 rad (500 Gy). In contrast, a distinct humoral regulator stimulating growth of GM-CSF/IL-3 factor-dependent (FD) hematopoietic progenitor cell lines was detected following radiation to doses above 2,000 rad. This humoral factor was not detectable in conditioned medium from irradiated cells, weakly detected using factor-dependent target cell populations in agar overlay, and was prominently detected by liquid co-cultivation of factor-dependent cells with irradiated stromal cell cultures. Subclonal lines of FD cells, derived after co-cultivation revealed karyotypic abnormalities and induced myeloblastic tumors in syngeneic mice. Five-eight weeks co-cultivation was required for induction of factor independence and malignancy and was associated with dense cell to cell contact between FD cells and stromal cells demonstrated by light and electron microscopy. Increases in hematopoietic to stromal cell surface area, total number of adherent cells per flask, total non-adherent cell colonies per flask, and cumulative non-adherent cell production were observed after irradiation. The present data may prove very relevant to an understanding of the cell to cell interactions during X-irradiation-induced leukemia.

Animals↗
PubMed1986

Persistent production of colony-stimulating factor (CSF-1) by cloned bone marrow stromal cell line D2XRII after X-irradiation.

The adherent stromal layer in long-term bone marrow cultures (LTBMC) provides the cellular environment necessary for the in vitro proliferation and differentiation of pluripotential hematopoietic stem cells. The role of humoral hematopoietic growth factors, colony-stimulating factors (CSF) in the regulation of hematopoietic cell production in this system is poorly understood. We have recently isolated and cloned an adherent cell line, D2XRII, derived from murine LTBMC. Plateau phase 25 cm2 cultures of 2 X 10(6) D2XRII cells in 8.0 ml produced CSF-1 (M-CSF) at around 100-150 units/0.1 ml medium. Following X-irradiation there was a dose-dependent decrease in the production of CSF-1 to a plateau of 50% of control levels at 10,000 rad. Higher doses did not produce a further decrease. The X-ray dose reducing CSF-1 production to 50% was 100-fold above the lethal dose as measured by clonagenic survival following trypsinization and replating. Trypsinized replated viable adherent but nondividing X-irradiated D2XRII cells were maintained for up to 8 weeks after irradiation and demonstrated continuous production of CSF-1. The data indicate significant divergence of two biologic effects of X-irradiation on plateau-phase marrow stromal cells: physiologic function of adherence and CSF-1 production, versus proliferative integrity. This divergence of effects may be very relevant to understanding the mechanism of X-irradiation-associated marrow suppression and leukemogenesis.

Animals↗
PubMed1986

Induction of growth alterations in factor-dependent hematopoietic progenitor cell lines by cocultivation with irradiated bone marrow stromal cell lines.

We studied the production of hemopoietins by x-irradiated plateau-phase cultures of cloned marrow stromal cell lines derived from C3H/HeJ marrow, termed D2XRII and clone 11. The production of CSF in agar overlay of control or 10,000 rad irradiated stromal cultures was quantitated by induction of colonies in: overlaid fresh marrow, IL-3-dependent cell line 32D cl 3, or GM-CSF/IL-3-dependent cell lines FDCP-1 or bg/bg cl 1. Conditioned media were tested for CSF by bioassay using fresh marrow cells, for M-CSF (CSF-1) by RIA, and for IL-3 and GM-CSF by microwell proliferation assay with 32D cl 3 and FDCP-1 cells, respectively. X-irradiation to doses that decreased CSF-1 to 40% of control levels (greater than 5,000 rad) resulted in a 30-fold increase in growth of FDCP-1 or bg/bg cl 1 cells in liquid co-culture or agar culture overlay with no detectable growth of 32D cl 3. The frequency of subculture of nonautocrine, factor independent (FI) variant clonal lines of FDCP-1 or bg/bg cl 1 cells was increased over 1000-fold by 15 weeks cocultivation with irradiated stromal cell cultures. FI subclonal lines formed tumors in syngeneic mice and contained no detectable poly A messenger RNA for GM-CSF or IL-3, and no elevation in c-myc, c-abl, c-src, or erb-B onc gene-specific messenger RNA compared to parent factor-dependent lines. These data indicate that x-irradiated plateau phase marrow stromal cells produce increased levels of cell contact-mediated biologically active hemopoietin(s) other than M-CSF, GM-CSF, or IL-3 and induce nonautocrine factor-independent malignant cell lines in vitro.

Animals↗
PubMed1986

Induction of malignant transformation of cocultivated hematopoietic stem cells by X-irradiation of murine bone marrow stromal cells in vitro.

X-irradiation of purified primary cultures of mouse bone marrow stroma or permanent cloned marrow stromal cell lines in plateau phase decreases production of macrophage progenitor cell-specific colony-stimulating factor to a plateau minimum of 40% of control levels after doses of 50 to 500 Gy delivered at 2 Gy/min. After 50 Gy there is increased bioavailability of another growth factor(s) that is distinct from macrophage progenitor cell-specific colony-stimulating factor, granulocyte-macrophage progenitor cell colony-stimulating factor, or colony-stimulating factor for multipotential hematopoietic stem cells (interleukin 3). Liquid-phase cocultivation of irradiated stromal cells with either nonadherent cells from continuous marrow cultures or cloned dual granulocyte-macrophage progenitor cell colony-stimulating factor/interleukin 3-dependent hematopoietic progenitor cell lines induces evolution over 5 weeks of factor-independent colony-forming cells. Subcultured factor-independent colonies generated clonal malignant cell lines with multiple distinct karyotypic alterations. Inoculation of 10(6) cells s.c. from factor-independent clones into syngeneic mice produces local granulocytic monomyeloid tumors with spread to spleen, lymph nodes, and bone marrow. These data provide the first demonstration in vitro of indirect X-irradiation leukemogenesis through cells of the marrow stroma.

Animals↗
PubMed1985

Results of therapy in adult acute nonlymphoblastic leukemia: experience in Jerusalem, Israel, during 1975-1982.

78 previously untreated patients (aged 16-82 years) with acute nonlymphoblastic leukemia received intensive chemotherapy for induction of remission. In 64 patients, the combination used consisted of daunomycin and cytosine arabinoside with or without 6-thioguanine. The overall remission rate was 59 and 87% for those who received what was considered as adequate therapy. Patients who achieved remission received maintenance and, in part, late intensification. The median duration of remission was 9 months. The median survival of the patients who attained remission was 24 months, compared to 15 months for the entire patient group and 3 months for patients who failed to achieve remission. Age had no effect on the rate and duration of the remission obtained but the median survival was significantly longer in patients below the age of 50 years.

Adolescent↗
PubMed1985

Biologic effects of in vitro X-irradiation of murine long-term bone marrow cultures on the production of granulocyte-macrophage colony-stimulating factors.

The production of colony-stimulating factor (CSF) by murine long-term bone marrow culture (LTBMC) was studied by a technique involving measurement of colony formation in agar overlay by fresh marrow target cells. Colonies were removed and microscopically examined for morphology and histochemistry. LTBMCs were exposed to x-irradiation at 200 rad/min prior to the overlay. Nonirradiated control LTBMCs induced 51.5 +/- 11 granulocyte-macrophage colonies per 2 X 10(5) target cells. Irradiation of LTBMCs to 6000 rad revealed a six-fold plateau-maximum increase in the number of colonies. There was occasional appearance of macroscopic mixed colonies containing granulocytes, macrophages, and megakaryocytes over irradiated but not control LTBMCs. Irradiated cells in the adherent stromal layer of LTBMCs continuously produced CSF that was detectable in the cell-free supernatants for up to seven weeks after irradiation and after doses as high as 10,000 rad. Shielding of the x-ray beam over half of the culture surface by a 10-half-value-layer lead block produced increased colony formation by target cells near the exposed surface area. The data indicate that CSF production by adherent cells within LTBMC persists after supralethal doses of x-irradiation. The mechanism of the increased colony formation by target cells overlaid on irradiated stromal cells involves factors relative to the local microenvironment.

Animals↗
PubMed1984

Acridinyl anisidide (m-AMSA) therapy in 11 patients with refractory acute leukemia.

Eleven patients with acute leukemia, refractory to all previous chemotherapy, were treated with acridinyl anisidide (m-AMSA). Seven patients received m-AMSA i.v. as a single agent at 150 mg/m2 daily for 4 to 7 days, and 4 patients received m-AMSA at 90 mg/m2 daily for 3 days in combination with thioguanine and cytosine arabinoside. Four of the nine patients with acute nonlymphoblastic leukemia responded to the treatment, and complete remission was obtained in three of them. One of these patients remained in complete remission 5 months after therapy. Three of the four responding patients received m-AMSA as a single agent. Two patients with resistant acute lymphoblastic leukemia did not respond. As in earlier trials with m-AMSA reported by others, about one-third of our refractory patients responded, which justifies the future use of this agent in refractory leukemia and in other regimens for the induction of remission in acute leukemia. Despite minimal cardiotoxicity of the drug, evidence of its cardiotoxic potential is recorded.

Adolescent↗
PubMed1983

Suppression of mixed lymphocyte reactivity by cellular and humoral factors in aplastic anemia--both before and after bone marrow transplantation.

A patient with infectious hepatitis who developed severe aplastic anemia received a bone marrow transplant from her HLA-identical, mixed lymphocyte culture (MLC)-negative sister. It was found that pretreatment of normal lymphocytes with the immunoglobulin fraction of the patient's serum resulted in marked inhibition of their proliferative response to mitogens, as well as their ability to serve as stimulators and responders in MLC. The patient's lymphocytes, unlike those of her HLA-identical sister were unable to stimulate and respond in MLC and markedly suppressed mixed lymphocyte reactivity between two unrelated healthy individuals. Donor-type lymphocytes obtained from the patient after engraftment were also unable to respond or stimulate in MLC. It is suggested that the suppression of lymphocyte responses was mediated by an immunoglobulin present in the patient's serum.

Adult↗
PubMed1983

Serum transcobalamin levels as an early indicator of bone marrow engraftment following transplantation.

Three B12 binding proteins, the transcobalamins TCI, TCII and TCIII, were determined serially in the serum of five patients who underwent bone marrow transplantation. The increase in TCII, followed by the increase in TCI, proved to be an early indicator of bone marrow regeneration, reaching a peak of up to twice its normal levels at least 5 d prior to the rise of the peripheral white blood cell count.

Adolescent↗
PubMed1982

Simultaneous presentation of plasma cell and monocytic leukemia with a subacute clinical course.

A rare case of simultaneous presentation of monocytic and plasma cell leukemia is reported. Cytochemistry, transmission and scanning electron microscopy confirmed the presence of a dual population consisting of monoblasts and plasma cells. Monoblasts contained nonspecific esterases, secreted lysozyme and showed dense bodies and surface ruffles under the scanning electron microscope, while the plasma cells secreted IgG kappa paraprotein, contained rough endoplasmic reticulum, and showed surface blebs with microvilli. Another unusual feature of this case was the relatively chronic course of the disease, lasting 15 months after initial diagnosis.

Acute Disease↗
PubMed1982

In vitro bioassay of erythropoietin using synchronized rabbit erythroid precursors.

Synchronized erythroid precursors obtained from the bone marrow of rabbits and plated in methyl-cellulose were used as a bioassay for the measurement of erythropoietin (Ep). Rabbits were given five daily injections of phenylhydrazine followed by a single dose of actinomycin-D. This treatment resulted in a rapid repopulation of bone marrow by synchronized erythroid precursors which can be stored at -180 degrees C for long periods. Grown in vitro for 2 days in the presence of added Ep these cells divided to form colonies (CFUE). The erythroid nature of these colonies was confirmed by 59Fe incorporation into heme. Preliminary studies indicate that this system is suitable for the measurement of Ep in human sera. It is simple, inexpensive, reproducible, and permits measurements at the physiologic range of Ep concentrations.

Animals↗
PubMed1981

Burkitt's lymphoma cell leukemia. Radiology and cytotoxic medication.

A 15-year-old girl presented with swelling and spontaneous bleeding of the gingiva. The lower anterior teeth were sensitive to percussion, and the lower lip and chin showed lack of sensation. Radiographically, gross loss of the alveolar and basal bone in both jaws was evident. The lamina dura and periodontal ligament had lost their morphology. Based on the clinical, radiographic and laboratory findings, the diagnosis of Burkitt's lymphoma cell leukemia was made. While cytotoxic medication brought about an immediate clinical improvement, radiographically, jaw bone repair became evident one month following initiation of treatment.

Adolescent↗