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Biomedical subjects

J F Loutit

Publications and source records attributed to J F Loutit.

At least 19 recordsLinked to original sources
PubMed1987

The induction by 239Pu of myeloid leukaemia and osteosarcoma in female CBA mice.

Plutonium-239 was injected into 12-week-old female CBA/H mice in the range 1.85-18.5 kBq kg-1 either as a single injection or as 16 injections spaced at 3.5 day intervals over eight weeks. There was a highly significant increase in the yield of fully developed osteosarcomas with increased amounts of 239Pu for both modes of injection. Osteosarcomas too small to be diagnosed radiographically were also seen in many bones and small but significant yields of myeloid leukaemia were seen in animals given plutonium. Although more myeloid leukaemia was seen in the mice given plutonium in divided amounts than in those given the plutonium in a single injection it could not be shown that multiple injection significantly affected the yield of either late effect.

Animals↗
PubMed1986

Induction of hypoxia in normal and malignant tissues by changing the oxygen affinity of hemoglobin--implications for therapy.

The drug BW12C, which increases the oxygen affinity of hemoglobin, reduces oxygen availability to tissues. This results in protection against radiation damage to the hemopoietic system and epidermal Langerhans cells in CBA mice. The drug also protects against beta-irradiation damage in pig epidermis. BW12C increases the hypoxic cell fraction in tumors and histological examination of an experimental T cell lymphoma shows that the induced hypoxia leads to tumor necrosis.

Aldehydes↗
PubMed1986

Radiation and haematopoiesis in Harwell steel mice.

Haematological information on steel (Sl) mice is limited largely to Sl/Sld mice of Bar Harbor stock (WC.B6 F1). Therefore, two Harwell alleles, SlgbH and Slcon, were investigated. In the steady state both heterozygotes were modestly anaemic, homozygous Slcon and compound Slcon/SlgbH more so. On perturbation by X-irradiation Slcon/SlgbH showed a decrease in median lethal dose (MLD)--6.5 Gy, Slcon/+ and Slcon/Slcon slightly less change (7.5 Gy) compared with +/+, 8 Gy. In recovery from sublethal doses single heterozygotes, double heterozygotes with Wv, and compounds showed no delay in restoration of the count of red blood corpuscles (RBC) such as that seen in typical W mice (e.g. Wv/+, W/Wv). Effects on Slcon/Slcon and Slcon/SlgbH differ from those reported for Sl/Sld in that they show normal growth of spleen colonies when used as lethally irradiated recipients of bone marrow, they support growth of implanted bone marrow to form radiation chimaeras. When Harwell steel mice are donors of bone marrow to lethally irradiated +/+ mice the chimaeras ultimately are not anaemic; when lethally irradiated Harwell steel mice are recipients of +/+ marrow they remain macrocytically anaemic. One deduces that, for normal development and production of normal RBC in the steady state, the erythron requires intrinsic factors determined by wild type alleles at the W locus and extrinsic factors determined by wild type alleles at the Sl locus. Mutant alleles at either locus may determine macrocytosis. Two mutant alleles at either locus are still more deleterious, often lethal. Whereas mutant W alleles may also influence the pluripotent haematopoietic stem cell (HSC) leading to reduced MLD on X-irradiation, a similarly reduced MLD for Sl mutants may represent an increased need for and consumption of products of the haematopoietic stem cells rather than truly increased radiosensitivity, since the Do for spleen colony-forming units is the same for Slcon/SlgbH as +/+ mice.

Animals↗
PubMed1985

A mouse beta-globin mutant that is an exact model of hemoglobin Rainier in man.

A mutation induced by ethylnitrosourea in a spermatogonial stem cell of a 101/H mouse has resulted in a structurally altered beta-diffuse major globin in one of his offspring. The mutant hemoglobin is associated with polycythemia, rubor, increased oxygen affinity and decreased hem-hem interaction. The mutant haplotype has been designated Hbbd4, polycythemia. Amino acid analysis of the mutant globin has shown that a single substitution beta 145 Tyr----Cys has occurred, and it is proposed that ethylnitrosourea induced an A----G transition in the tyrosine codon (TAC----TGC). This murine polycythemia is homologous with hemoglobin Rainier in man, in which the amino acid substitution is also beta 145 Tyr----Cys and which is associated with similar physiological consequences.

Animals↗
PubMed1985

The gene triplet Rw W Ph controls murine haematopoiesis.

Having shown a haematopoietic role for Patch (Ph), especially when doubly heterozygous with the mutant Wct (Loutit & Cattanach, 1983) we have similarly examined the Rw locus, the third member of the triplet. Mature Rw/+mice have a just detectable macrocytic anaemia. When doubly heterozygous with Wct and Wv the mild anaemia of these W mutants is exaggerated but with W19H (not anaemic as single heterozygote) red cell factors are as for Rw/+. Rw/+mice are strikingly more sensitive to the lethal effects of X-irradiation (MLD 6.66 +/- 0.10 Gy) on haematopoiesis than comparable +/+ mice (MLD 8 Gy). Those mice that do recover after X-irradiation do not exhibit the delay in recovery of erythropoiesis that is evident with characteristic W mutants in both single and double dose. Furthermore the double heterozygote Wct+/+Rw has a significantly lower MLD (5.19 +/- 0.17 Gy) for X-radiation than Wct/+ (MLD 6.48 +/- 0.24 Gy). We argue that all three loci W, Ph and Rw, influence haematopoietic stem cells, leading to increased radiosensitivity when deletions or mutant genes are present.

Anemia, Macrocytic↗
PubMed1985

The induction by 224Ra of myeloid leukaemia and osteosarcoma in male CBA mice.

Radium-224 was injected into 12-week-old male CBA mice in the range 2-64 kBq per mouse either as a single injection or as eight injections spaced at 3.5 day intervals over 4 weeks. Small but significant yields of myeloid leukaemia or osteosarcoma were obtained in all but the control groups. An effect of mode of administration (single or multiple injections) could not be demonstrated but the combined results showed: a maximum yield of myeloid leukaemia in the region 8-16 kBq 224Ra; a greater yield of osteosarcoma than myeloid leukaemia at 64 kBq 224 Ra injected.

Animals↗
PubMed1984

The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80: macrophages of bone and associated connective tissue.

The macrophage-specific antigen F4/80 has been localized in adult mouse bone and connective tissue. F4/80 positive cells form the centre of haemopoietic islands, line the periosteal and subendosteal bone surfaces and are a major component of connective tissue and the synovial membrane (presumptive type A cells). F4/80 is absent from fibroblasts, chondrocytes, osteoblasts, osteocytes, osteoclasts and a subpopulation of synovial lining cells (presumptive type B cells).

Animals↗
PubMed1982

Versatile stem cells in bone marrow.

The question of whether there is a single pluripotent haemopoietic stem cell or a variety of stem cells each with a capacity for self-replication is still unresolved. Evidence from radiation-chimaeras and from patients with marrow grafts indicates that haemopoietic stem cells are not a homogeneous population. It is suggested that in marrow there is a variety of stem cells, some controlled by recognised factors and others by as yet unknown factors. It is postulated that some of these cells are pluripotent, whereas others are differentiated for a single line, so both polyphyleticists and monophyleticists may have been partly right.

Animals↗
PubMed1982

Mast cells in spotted mutant mice (W Ph mi).

Mast cells derived from haematopoietic tissue are deficient in numbers in spleen, stomach and skin of Harwell mice doubly mutant at the spotting W locus: seven viable combinations of four mutants. Most combinations have variably impaired viability, anaemia and infertility; but homozygous WshWsh are normal in these respects yet still lack mast cells. The effect of the W gene on mast cells acts in recessive fashion. Effects of doubly mutant W genes on mast cells and coat colour, the latter usually regarded as dominant, appear more closely related than other pleiotropic effects. The spotting gene Ph, closely linked to W, has but marginal effects on mast cells, whereas mi, another spotting gene, quite unrelated to W affects mast cells in the spleen in a dominant way. Thus, splenic mast cells may be a special category of a heterogeneous population. Peptic ulceration, recorded in W/Wv mice of Jackson stock, was not seen in Harwell mice. We suggest that this lesion is due to genetic complementation or environmental causes.

Animals↗
PubMed1982

Tissue repopulation during cure of osteopetrotic (mi/mi) mice using normal and defective (We/Wv) bone marrow.

Resorption of petrotic bone in osteopetrotic (mi/mi) mice was brought about by transplantation of bone marrow to X-irradiated recipients. In an attempt to learn more about the donor cell line involved in this process, both normal and defective marrow were used. The consequent repopulation of the lympho-myeloid complex was monitored by isoenzymes of glucose phosphate isomerase. The progress of normal marrow grafts was contrasted with that of a defective marrow (We/Wv). Despite the observation with We/Wv marrow showed reduced ability to form colonies in the spleen of an irradiated recipient, this marrow was as effective as normal marrow in inducing resorption of petrotic bone. The primordial stem cell for the osteoclast (haematopoietic stem cell?) is thus not a CFUS. Chimaeras with resolution of osteopetrosis by We/Wv bone marrow may exhibit erythropoiesis from residual stem cells of the host but leucocytes and platelets from the donor.

Anemia, Macrocytic↗
PubMed1981

Colony forming units and haematopoietic stem cells in osteoclastopoiesis.

HSC and CFUs are not identical. HSC are no longer considered to be a homogeneous population but an age-structured spectrum of cells (Schofield, 1978). CFUs, which have been identified only in rodents and with certainty only in mice, may be a sub-set of HSC required by mice, perhaps controlled by the W locus and virtually eliminated in double W mutants. A dichotomy of CFUs and HSC has also been demonstrated by Wiktor-Jedrzejczak et al. (1977); ++ bone marrow treated with anti-Thy 1.2 serum lost its curative properties for W Wv anaemic mice with CFUs being unaffected.

Animals↗
PubMed1979

Resorption of bone.

The cell-system responsible for resorption of bone is now considered to be a derivative of haematopoietic bone-marrow, not skeletal connective tissue. Consideration of mutant mice and rats, with defects of bone resorption giving osteopetrosis, suggests that the primary defect is of the professional scavengers, the mononuclear-phagocyte system, failing to recognise effete bone. To explain associated defects of thymic lymphocytes it is postulated that the mononuclear-phagocyte system may be activated to a major or minor extent by professional recognisers, thymic lymphocytes, as happens in some inflammatory reactions.

Animals↗
PubMed1979

A functional assessment of macrophages from osteopetrotic mice.

Macrophages from osteopetrotic mice caused less bone resorption than normal sib macrophages in culture. The bone-resorbing activity lay in the culture supernatant, and reduced activity in cultures of macrophages from osteopetrotic mice correlated with reduced glass spreading and reduced latex phagocytosis. We suggest that macrophages from osteopetrotic mice show defective phagocytic recognition of glass, latex, and bone and that this defective recognition may reflect the cause of the failure of resorption which results in osteopetrosis.

Acid Phosphatase↗