Search PubMed⌕ Search

Biomedical subjects

J F Loutit

Publications and source records attributed to J F Loutit.

At least 37 records · Page 2Linked to original sources

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↗

Longevity of osteoclasts in radiation chimaeras of beige and osteopetrotic microphthalmic mice.

Beige (bg/bg) mice lethally X-irradiated (900 or 1000 rad) and rescued with spleen cells from osteopetrotic (mi/mi) mice were examined periodically up to 6 months thereafter for signs of osteopetrosis, radiographic and histological. Their metaphyses were also examined electromicrographically for general characteristics of osteoclasts and for giant lysosomal granules. Measurements of lysosomal area indicated no change in the first weeks, then an exponential decline to near base line after 3 months with a half-period of or approximately 10 days. In this combination osteopetrosis was of slower progression than hitherto reported in C57BL mice. We suggest that osteoclasts have no fixed life span and that their longevity is a function of genetic background and perhaps operational needs.

Animals↗

Longevity of osteoclasts in radiation chimaeras of osteopetrotic beige and normal mice.

Beige mice, osteopetrotic from incorporated mi/mi genes, and their skeletally normal siblings were X-irradiated and converted to radiation chimaeras by rescue with normal CBA bone marrow. The procedure produced rapid cure of the osteopetrosis. Electron micrographic measurement of the decline in giant lysosomes of the host mice indicated that the longevity of the host's osteoclasts was up to 30 days in the osteopetrotic and 40 days in the skeletally normal mice. In each case the decline was roughly exponential with half-times of about 6 and 8 days respectively. Monogenetic and perhaps polygenetic and teleological factors are invoked. Absence of a latent period before decline in the score seen in the companion paper is attributed to the presence of partially mature osteoclast precursors in bone marrow, not present in spleen.

Animals↗

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↗

Osteoclasts derived from haematopoietic stem cells.

The origins of the multinucleated osteoclast have been controversial, with osteogenic precursors and haematopoietic stem cells as candidates. Recent evidence for the latter is persuasive but circumstantial. We report here direct evidence obtained in radiation chimaeras from a natural cytoplasmic cell marker transmitted by the donated haematopoietic stem cell.

Animals↗

Giant lysosomes, a cytoplasmic marker in osteoclasts of beige mice.

The beige mouse (bg/bg) is an analogue of the Chediak-Higashi syndrome (CHS) in man. The disorder is characterised by the presence of enlarged cytoplasmic granules, said to be lysosomes, in many cell types. The present report describes giant lysosomes defined as lysosomes greater than 1.0 micrometers in diameter, in osteoclasts of beige mice. The giant lysosomes contained both acid phosphatase and aryl sulphatase and were present in osteoclasts of beige mice aged from at least 4 days to 3 months. There is some evidence that the giant lysosomes form by fusion of smaller structures. Since giant lysosomes were also seen in osteoclasts from mouse strains not suffering from CHS, e.g., CBA mice, a quantitative survey was carried out. It was shown that osteoclasts from beige mice aged from 4 days to 3 months contain significantly increased numbers of giant lysosomes when compared with osteoclasts from CBA mice and CBAXbg/bg F1 hybrids. The giant lysosomes of the beige mouse osteoclast are currently being used as cytoplasmic markers in experiments on the cell of origin of the osteoclast.

Acid Phosphatase↗

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↗

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↗

Resolution and relapse of osteopetrosis in mice transplanted with myeloid tissue of variable histocompatibility.

Osteopetrotic microphthalmic mice (mi/mi) were treated by injections of suspensions of myeloid tissue, newborns i.p., and weanlings i.v. Donated syngeneic material effected permanent cure of oteopetrosis provided that the dose was large enough (10(8) cells of bone marrow). H-2-compatible allogeneic bone marrow was initially as effective, but relapse ensued in immunocompetent mice. H-2-incompatible marrow was ineffecitve except in one set of newborn tolerant mice. Total body X-radiation in sublethal doses to recipients allowed permanent cure with H-2-compatible, and, in one circumstance, with H-2-incompatible marrow in smaller doses. The best results were obtained after lethal irradiation and the smaller dose of marrow. Results were checked by chromosome assay demonstrating that cure or relapse was correlated with permanent take or rejection, respectively, of a transplant in a recipient's bone marrow. Retention of donor lymphocytes alone was not associated with effective bony resorption; the candidate cell line for effectiveness remains the haematopoietic stem cell-monocyte-tissue phagocyte.

Animals↗

Radiation leukaemogenesis: is virus really necessary?

Generalized lymphosarcomatosis (leukaemia) of non-thymic type occurs in mice bearing 90Sr or 239Pu or 226Ra. Tumours passaged from such mice have been tested for tumour-associated transplantation antigens that could provoke a protective immunity which would be expected if such antigens were determined by virus activated by the irradiation. Sub-threshold doses of living syngeneic tumour, large doses of living allogeneic tumour and large doses of killed syngeneic tumour were without protective effect. This suggests that viruses observed electron micrographically in such tumours are passengers and not causative.

Animals↗

Lymphoid tumours and leukaemia induced in mice by bone-seeking radionucleides.

Single intraperitoneal doses of soluble 90Sr and monomeric 239Pu induced generalized lymphomatosis in laboratory mice. Leukaemogenesis due to soluble 226Ra was more uncertain. Clinical expression was variable, but as a generalization the disease was a lymphosarcoma with haematogenous (leukaemic) spread. Only rarely, unlike the commonly recorded forms of natural and X-ray-induced lymphosarcomas, was the thymus apparently the site of onset. The cell-type was lymphoblastic of undifferentiated null form (not T, not B). The average doses of alpha or beta radiation accumulated in the bone-marrow, the presumed site of induction, were at the time of diagnosis usually more than 2500 rad, but, if the cases occurring after radium or low activities of plutonium are accepted as induced, 300-1500 rad of alpha radiation. Mice converted to chimaeras only rarely exhibited any lymphoma, general or local. Abdominal lymphomas were not numerically increased by these radionucleides (perhaps due to shortening of life-span) though some may have been prematurely induced.

Animals↗

The ultrastructure of skeletal haemangiosarcomas induced in mice by strontium-90.

The commonest skeletal tumour occurring in male CBA and C3H mice injected with 7--13 muCi 90Sr (per mouse) at Harwell was diagnosed with the light microscope as haemangiosarcoma. On the other hand, Nilsson, using male CBA mice injected with similar amounts of 90Sr, recorded the predominant tumour as fibroblastic osteosarcoma. To resolve the apparent discrepancy, samples of non-osteogenic tumours induced by 90Sr at Harwell were examined with the electron microscope and their ultrastructure compared with that described for fibroblastic osteosarcoma by Nilsson. The tumours diagnosed as haemangiosarcoma at Harwell showed ultrastructural features not observed in the fibroblastic osteosarcomas. Vasoformation was marked, the vascular channels varying in shape, size and in the character of their lining cells. Some vascular channels were lined by cuboidal cells, crowded together, and surrounded by a basement membrane. Others were lined by an attenuated endothelium and often formed networks. The tumour cells showed great variation in shape, size and ultrastructure and were sometimes enclosed by a basement membrane. Thus the ultrastructure of the tumours described in this report supports the diagnosis of haemangiosarcoma, rather than fibroblastic osteosarcoma. The question of whether these haemangiosarcomas truly originate from vascular endothelium, or are mimics, is discussed.

Animals↗