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M L Labat

Publications and source records attributed to M L Labat.

At least 37 records · Page 2Linked to original sources
PubMed1986

Excess of lympho-reticular cell complexes in the bone marrow linked to T cell mediated dysmyelopoiesis.

The term dysmyelopoietic syndrome (DMPS) covers a variety of closely related disorders with various etiological factors, and characterized by chronic (pan) cytopenias whose prognosis and treatment are still controversial. Despite the recent efforts to identify pathogens, effector cells and soluble cell products involved in the development of this syndrome only a few comprehensive experimental data are available, useful for elaboration of therapeutic regimens. We describe here a patient with DMPS who was refractory to inductive chemotherapy. Initial agar gel culture studies revealed the activity of hematopoiesis inhibitory T cells within the bone marrow that could be suppressed by prednisone both in vitro and in vivo. However another pathological cell features, the excess of an unusual lympho-reticular cell complexes was identified in long-term liquid cultures. These symbiotic cell complexes persisted throughout the disease, despite the prednisone induced hematological remission, suggesting their causative role in the disease, that more recently progressed towards acute myeloid leukemia.

Adult↗
PubMed1985

[Osteopetrosis].

Animal models of osteopetrosis have led us to consider this condition to be an immune disease. In both the hereditary from in the op/op mutant rat and in experimentally induced from by Cl2MDP, osteopetrosis is associated with immune deficiencies, such as the inhibition of the mitogenic response of T lymphocytes, the inability to develop adjuvant arthritis. In particular, the differentiation of the thymus dependent macrophages is inhibited in the mouse treated with Cl2MDP. These animal models illustrate the relationships between the immune system and the bone regeneration system. They enable the study of the relationship between T lymphocytes, macrophages and osteoclasts.

Animals↗
PubMed1984

Dichloromethylene diphosphonate (Cl2MDP) reduces natural killer (NK) cell activity in mice.

Daily administration of dichloromethylene diphosphonate (Cl2MDP) to (C57BL/6 X DBA/2) F1 hybrid mice, from two days of age (10 mg of P/kg body weight), resulted in a marked impairment of natural killer (NK) activity of spleen cells against YAC-1 lymphoma cells. The suppressive effect increased with the duration of the treatment. Cessation of the treatment led to a rapid recovery (in 2 weeks) of NK activity while the osteopetrotic bone lesions persisted. Thus, the loss of natural killing cannot be explained by the simple reduction of bone marrow volume secondary to Cl2MDP-induced osteopetrosis. However, as NK cells are considered to be dependent on the bone marrow because they cannot be sustained by extramedullary production, a direct effect of Cl2MDP on the generation of NK cell precursors by the bone marrow was not excluded. Cl2MDP was not directly toxic to the fully differentiated splenic NK cells, since the addition of Cl2MDP to the in vitro assay (10(-5)-10 micrograms/ml) did not reduce cytotoxicity. These studies suggest that impairment of NK activity during Cl2MDP treatment may have clinical toxicologic implications since NK cells have been suggested to play an important role in natural host defenses against infection and neoplasia.

Animals↗
PubMed1983

(Dichloromethylene)diphosphonate-induced impairment of T-lymphocyte function.

The daily subcutaneous administration of (dichloromethylene)diphosphonate (clodronate) to 3-day-old normal inbred Wistar-Furth rats for 30 days produces osteopetrotic bone lesions resembling those of the osteopetrotic mutants. Furthermore, tooth eruption is prevented, growth slows down, and signs of runt disease appear. The weight of the thymus is decreased, and T cells from the thymus and spleen respond weakly to mitogens. These thymic disorders associated with defective bone resorption are very similar to those previously reported in the osteopetrotic mutant op rat and support the hypothesis of a link between the thymus and normal bone modeling and remodeling.

Alkaline Phosphatase↗
PubMed1983

Lack of a T-cell dependent subpopulation of macrophages in (dichloromethylene) diphosphonate-treated mice.

In Cl2MDP-osteopetrotic mice, one subpopulation of thioglycollate-induced peritoneal exudate macrophages (M phi) is missing. This subpopulation is precisely the one whose differentiation is known to be dependent on T-lymphocytes, as it is also missing in the athymic nu/nu mice. Cl2MDP-induced osteopetrosis being partially attributable to deficient osteoclastic bone resorption, raises the possibility that this missing M phi subpopulation might represent the precursors of osteoclasts. It is suggested from this work that the interplays between T-cells and M phi, so well known in immunity and inflammation, may also be relevant to osteoclastic differentiation and therefore, to bone remodeling.

Animals↗
PubMed1983

A baby with Di George syndrome treated with bovine thymic extracts: a 3.5 yr analysis of variations in the distribution of lymphocytes characterized by three tests of cell mediated immunity and electrophoretic mobility.

This report concerns a baby with the features of Di George syndrome. Bovine thymic extracts prepared in this laboratory were used to treat the baby between the ages of 1 and 18 months. A favourable evolution of the illness was noticed, suggesting the diagnosis of Di George syndrome in its partial form and/or a favourable response to the treatment with thymic extracts. The number of E-rosette forming T-lymphocytes in blood remained low during the 3.5 yr of the observation. The in vitro response of peripheral blood lymphocytes to phytohemagglutinin and to allogenic cells slowly increased during this period of time. Surprisingly, no change in the proportions of lymphocytes of high electrophoretic mobility and low electrophoretic mobility was observed, in contrast to the gradual change usually observed in normal individual age-matched controls.

DiGeorge Syndrome↗
PubMed1982

Gene dependent differences in malignant osteopetrosis as evidenced by cellular induction of the disease.

Osteopetrosis was induced in lethally irradiated normal rats by cell infusion prepared from spleens of the osteopetrotic (op) mutant littermates. However, similar attempts to induce osteopetrosis in another strain of osteopetrotic rats, namely the "toothless" (tl) rats, were unsuccessful. This discrepancy between op and tl rats with regard to the transmission of the disease to normal littermates, parallels the response of the respective mutants to treatment by normal bone marrow cells: the op rat is cured, not the tl rat. The present findings confirm the cellular origin of osteopetrosis in the op rat, whereas the origin of the defect in the tl mutant remains obscure.

Animals↗
PubMed1982

Resistance to adjuvant arthritis induced by a genetic mutation, osteopetrosis.

Adjuvant arthritis stands as the closest model to human rheumatoid arthritis. A genetic mutation (op) recognized to provoke osteopetrosis in rats, completely inhibits their ability to develop adjuvant arthritis. Osteopetrosis in the op mutant is linked to deficiencies in T-lymphocytes and macrophages functions. Therefore this animal model may be helpful for a better understanding of the immunoregulation impairment involved in adjuvant arthritis.

Animals↗
PubMed1981

Osteopetro-rickets: a new congenital bone disorder.

Two lethal mutations have been described in the rat: "osteopetrosis" (op) and "toothless" (tl). The op mutant can be cured by normal bone marrow infusion, while the tl mutant cannot. We report here additional data with regard to the tl mutant. The bone disease of the tl rat as in the op rat is associated with a precocious thymic atrophy, but bone lesions are quite different. In addition to classical osteopetrosis, the tl rat displays several features of rickets: broadening of the extremities of long bones, thickening of the epiphyseal plates, presence of osteoid areas. In addition, the persistence of embryonic characters, evidenced by high levels of alpha-fetoprotein, suggests that the developmental defect of bone is part of a more general process.

Alkaline Phosphatase↗
PubMed1980

[Thymus and bones].

Rat congenital osteopetrosis and cyclophosphamide (an immunosuppressive drug) induced osteocondensation are useful experimental models for the understanding of the relationships which seem to exist between thymus and bone. The high levels of seric alphafetoprotein found in the osteopetrotic tl rat raise the question of the persistance of embryonic characters in congenital osteopetrosis.

Animals↗
PubMed1979

Osteopetrosis reconsidered as a curable immune disorder.

Osteopetrosis is a unique model for investigating osteoclast formation from lymphocytes and more precisely from T-lymphocytes. In the pathogenesis of this condition, a thymic impairement must be postulated. The cure of several osteopetrotic animal mutants and an infant suffering from juvenile malignant osteopetrosis by injecting normal marrow are the first examples of the successful management of a bone disorder by cell injection.

Animals↗
PubMed1977

Immunological defect and its correction in the osteopetrotic mutant rat.

Congenital osteopetrosis in the mutant rat "op" is accompanied by early atrophy of the thymus gland. The response of thymocytes to concanavalin A and phytohemagglutinin P was greatly diminished at age 28 days, even before pronounced thymic atrophy could be detected. The response of spleen cells to mitogens that stimulate thymus-derived (T) and bone-marrow-derived (B) cells was diminished as early as 35 days of age. A single injection of a suspension of normal bone marrow, which cures osteopetrosis, increased thymus weight and restored the normal responses of both thymus and spleen to various mitogens. These results add further support to the hypothesis that the thymus is involved in the pathogenesis of osteopetrosis.

Age Factors↗
PubMed1977

[Arrest of dental development in the osteopetrotic rat and the healing effect of normal bone marrow].

The development of the osteopetrotic "op" rat's mandible was examined from birth to 4 months of age. Before birth the growth of incisors is disturbed and after birth the molar growth stops. Bone resorption is severely reduced and enamel formation ceases soon on the inferior aspect of the incisor, due to degeneration of ameloblasts and lack of vascularisation. A single injection or normal bone marrow cured the disorder at the long bone level within 2-3 months and had a beneficial effect in re-establishing the growth of dental tissue, yet without leading to tooth eruption.

Amelogenesis Imperfecta↗