PCDOSE: an interactive software system to calculate internal radiation dose on a personal computer.

An interactive, menu directed, software system to calculate committed dose equivalents for individuals with different physiques after inhalation, ingestion or injection of radionuclides has been developed. The calculations are based on ICRP 26/30 methods. The programs are written in PASCAL and can be implemented on a personal computer with a MS-DOS operating system and a hard disk with a storage capacity of at least 20 Mb.

In vivo development of an acetyldinaline resistant subline of the BN rat acute myelocytic leukemia (BNML).

The cytostatic drug acetyldinaline [ACD, CI-994, 4-acetylamine-N-(2-aminophenyl)-benzamide] shows an extreme antileukemic effect in the Brown Norway (BN) rate model for acute myelocytic leukemia (BNML) with only minor toxicity for normal pluripotent hemopoietic stem cells. So far, the mode of action is unknown. A resistant subline (BNML/ACD-R) was developed in vivo in the BNML model.

The expression of cytokine receptors by purified hemopoietic stem cells.

Sorted fractions from mouse bone marrow containing highly purified hemopoietic stem and progenitor cells were studied for the expression of growth factor receptors. With the use of rhodamine 123 WGA+, 15-1.1-, low density cells were separated into quiescent pluripotent stem cells and committed progenitor cells.

In vitro resistance of the brown Norway rat acute myelocytic leukemia (BNML) to lymphokine-activated killer activity.

In in vivo allogeneic bone marrow transplantation studies with the Brown Norway (BN) rat as recipient and the WAG/Rij rat as allogeneic donor a significant graft-versus-leukemia (GVL) effect is observed. Studies were performed to investigate whether lymphokine-activated killer (LAK) cells play a role in this GVL effect. Splenocytes from WAG/Rij and BN rats were activated in vitro by recombinant human interleukin-2 (rhIL-2) for 5-6 days.

Treatment of experimental allergic encephalomyelitis in rats with total body irradiation and syngeneic BMT.

Experimental allergic encephalomyelitis (EAE) was induced in Buffalo rats by immunization with syngeneic spinal cord homogenate in complete adjuvant. EAE, an autoimmune disease of the central nervous system (CNS), is regarded as a model for multiple sclerosis. When severe paresis had developed, rats were treated with high-dose total body irradiation (TBI) and transplanted with syngeneic BM from healthy donors.

Mercuric chloride down-regulates T cell interferon-gamma production in brown Norway but not in Lewis rats; role of glutathione.

Injection of a low dose of mercuric chloride into Brown Norway (BN) rats caused a marked decrease in the concanavalin A (ConA)-induced generation of interferon-gamma-producing cells (IFN-gamma pc) in spleen cell cultures prepared 1 h after mercury administration. A second injection 48 h later caused a further diminution of IFN-gamma pc down to 30% of the number generated in splenocyte cultures of phosphate-buffered saline (PBS)-injected controls. Injection of Lewis rats with either one or two doses of HgCl2 revealed no inhibitory effect on splenic IFN-gamma production.

Factors affecting the transduction of pluripotent hematopoietic stem cells: long-term expression of a human adenosine deaminase gene in mice.

An amphotropic retroviral vector, LgAL(delta Mo + PyF101) containing a human adenosine deaminase (ADA) cDNA was used to optimize procedures for the lasting genetic modification of the hematopoietic system of mice. The highest number of retrovirally infected cells in the hematopoietic tissues of long-term reconstituted mice was observed after transplantation of bone marrow (BM) cells that had been cocultured in the presence of both interleukin-1 alpha (IL-1 alpha) and IL-3. A significantly lower number was detected when IL-1 alpha was omitted from such cocultures.

Leukemic cell kill in autologous bone marrow transplantation: in vivo or in vitro?

Both the contribution of high dose chemo-radiotherapy ("conditioning treatment") prior to autologous bone marrow transplantation (ABMT) and "purging" of autologous marrow grafts to the prevention of leukemia relapse are being addressed in the present communication. Based on both preclinical and clinical studies, it is concluded that cures achieved after ABMT are mainly due to effective eradication of residual leukemic cells in the host. The chance that leukemia will relapse is due to leukemic cells reinfused with the graft is estimated to be less than 10%.

L4415: further characterization of the rat model for human acute lymphocytic leukemia.

The biological properties of a transplantable lymphocytic leukemia, L4415 in the WAG/Rij rat, are described. The radiation-induced L4415 leukemia is characterized as a relatively slowly growing, non-immunogenic, immature T-cell leukemia which shows a reproducible growth pattern upon intravenous (i.v.

Evidence for bovine leukemia virus infection of peripheral blood monocytes and limited antigen expression in bovine lymphoid tissue.

Bovine leukemia virus (BLV) infection of cattle is a common but inapparent retrovirus infection from which less than 5% of infected cattle manifest clinically with lymphoma. During the course of life-long infection, cattle maintain a high anti-BLV titer during an apparent latent infection of B cells from which proviral DNA but not transcripts can be detected. To investigate if BLV infection is truly latent and restricted only to B lymphocytes, peripheral blood leukocytes were purified from cattle with naturally acquired BLV infection with various stages of subclinical and clinical disease.

Responses of cultured mammalian cells to prolonged low dose rate gamma irradiation.

Experiments were performed to verify the finding of others that prolonged irradiation caused sudden death of cells. Continuous irradiation (dose rate 0.09 Gy/h) was applied to the R-1, RUC-2, V79 and T-1g cells for up to 140 days.

Comparison of protection from homologous cell-free vs cell-associated SIV challenge afforded by inactivated whole SIV vaccines.

This study attempted to determine if SIV vaccines could protect against challenge with peripheral blood mononuclear cells (PBMCs) from an SIV infected rhesus monkey. Mature Macaca mulatta were vaccinated four times with formalin inactivated SIVmac32H administered in MDP adjuvant (n = 8) or SIVmac32H ISCOM vaccine (n = 8). Controls included animals vaccinated with measles virus in MDP adjuvant (n = 4) or ISCOM (n = 4) preparations.

Detection of migrated allogeneic oligodendrocytes throughout the central nervous system of the galactocerebrosidase-deficient twitcher mouse.

Galactocerebrosidase-deficient oligodendrocytes of 'twitcher' (twi/twi) mice degenerate prematurely. Transplantation of normal bone marrow cells has been shown to alleviate symptoms and to prolong survival time. However, characteristic ataxia ('twitching') is not cured.

Minimal residual disease in leukemia: state of the art 1991.

Recent achievements in decreasing the detection level of "minimal residual disease" in leukemia are summarized both in a relevant rat model for acute myelocytic leukemia (BNML) and in the human leukemias. Detection levels as low as 1 leukemic cell per 10(8)-10(9) and 10(5)-10(6) normal bone marrow cells have become realistic in the animal model and in human leukemia, respectively. The implications of these new tools for detecting hidden leukemic cells are discussed.

Models for the electronic processing of flow cytometric data at high particle rates.

In flow cytometry at high particle rates, complete processing of data is limited by the capacity of the flow cytometer electronics which are constrained by the waiting or cycling time of the processor. Four models of impulse processors were analyzed to study the influence of the waiting time and reset mechanisms on the input-output properties of commonly used electronic devices. The models contain a feedback loop to represent a waiting time and describe reset mechanisms to filter trains of consecutive pulses such as clumps and doublets.

Experimental and clinical gnotobiotics: influence of the microflora on graft-versus-host disease after allogeneic bone marrow transplantation.

One of the major complications of allogeneic bone marrow transplantation (BMT) is graft-versus-host disease (GvHD), which is caused by donor type lymphocytes which react against the recipient's tissues. An important factor which influences GvHD is the recipient's gastrointestinal microflora. This was originally observed in gnotobiotic mice.

Relative biological effectiveness for neutron carcinogenesis in monkeys and rats.

The risks of total-body irradiation with large doses of X rays (average dose 6.7 Gy) and fission neutrons (average dose 3.4 Gy) were investigated by keeping a group of long-term surviving monkeys from an experiment on acute effects under continuous observation.

Autoimmunity in non-human primates: the role of major histocompatibility complex and T cells, and implications for therapy.

Two autoimmune disease models were studied in rhesus monkeys: type II collagen-induced arthritis (CIA) and experimental allergic encephalomyelitis (EAE). Unrelated outbred animals were used in these studies. In both models disease resistant and susceptible individuals could be identified.

Culture of hematopoietic stem cells purified from murine bone marrow.

The results of the Y-chromosome in situ hybridization experiments, the MRA assessment, and the long-term production of CFU-GM in vitro indicate that our protocol to sort low density WGA+, 15/1.1-, Rh123 dull cells enriches about 200-fold for PHSC. Assays for spleen colony formation (CFU-S) and radioprotection (30-day survival) were shown to be unspecific for PHSC, and, therefore, we lack a quantitative PHSC assay.

Quantification of mitoxantrone in bone marrow by high-performance liquid chromatography with electrochemical detection.

An analytical method for the determination of mitoxantrone in bone marrow was developed using high-performance liquid chromatography with electrochemical detection. The extraction procedure was optimized by investigating several factors which potentially could influence the recovery of mitoxantrone from bone marrow cells. The mean recovery of mitoxantrone from rat bone marrow was found to be 81.

Construction and expression of an adenosine deaminase::lacZ fusion gene.

A eukaryotic expression vector was constructed in which the coding nucleotide sequences (ADA) of human adenosine deaminase (ADA) were fused in frame with the coding sequences of the bacterial gene lacZ encoding beta-galactosidase (beta Gal). This ADA::lacZ fusion gene was anticipated to encode a hybrid protein that has retained the biological functions of both proteins. Transfection of mammalian cells with the fusion gene resulted in the synthesis of both ADA and beta Gal.