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Biomedical subjects

C Rosse

Publications and source records attributed to C Rosse.

At least 55 records · Page 3Linked to original sources
PubMed1981

The dependence of tumor neutralization on bone-marrow-derived cells.

Radiosensitive host cells capable of potentiating tumor neutralization by immunocytes in normal recipients are present only in the bone marrow and not in the spleen or thymus. This was shown by selectively eliminating either the bone marrow, spleen or thymus of groups of mice and then subcutaneously injecting these animals with sensitized splenocytes and tumor cells. Bone marrow ablation was accomplished by the administration of the bone-seeking radioactive isotope 89Sr which did not reduce thymic or splenic cellularity. Sensitized splenocytes completely inhibited the growth of admixed tumor cells in normal, nude, splenectomized, or 88Sr-treated animals, but the sensitized cells were as ineffective in 89Sr-treated recipients as in 900-rad irradiated mice. Bone marrow cells of normal donors admixed with sensitized splenocytes and the sensitizing tumor cells caused a significant inhibition of tumor growth in 900-rad and 89Sr-treated mice. Therefore, the radiation-sensitive host cells that potentiate the tumor-inhibitory effect of sensitized splenocytes are unique to the marrow and, in the intact animal, apparently emigrate from this organ to interact with sensitized immunocytes at the site of tumor growth.

Animals↗
PubMed1981

Deficiency in cells expressing terminal transferase in autoimmune (motheaten) mice.

The extensive breakdown of immune homeostasis in the motheaten mouse (me/me) has been ascribed to a single gene defect on chromosome 6 (ref. 1). These mice develop skin lesions within the first week of life, do not thrive, and die within the first 3--8 weeks. There is severe hypergammaglobulinaemia with multiple species of circulating autoantibody and deposition of immune complexes in the thymus, skin, lungs and kidneys. A single gene defect producing such catastrophic results may provide an important model for understanding autoimmune phenomena. We report here a virtual absence of terminal deoxynucleotidyl transferase-positive (TdT+) cells in the bone marrow, thymus and spleen of motheaten mice. TdT is a DNA polymerase which has the unique capacity to polymerize nucleotides in the absence of template direction. Although no in vivo biological function of this enzyme has been established, its unique appearance in the bone marrow and thymus of adult mammals and its in vitro biochemical activity have led to a proposed role for TdT in the somatic diversification of lymphocytes. Bone marrow TdT+ cells have been shown to belong to both T and B cell populations and may also include precursor cells common to these lineages. Although the role of TdT in the acquisition of appropriate T- and B-cell specificities is not known, our results are the first to correlate the virtual absence of TdT+ cells with a severe autoimmune syndrome. We investigated the level of TdT+ cells in neonatal me/me mice and their normal littermates and the susceptibility of TdT+ cells to circulating autoantibody in motheaten mouse serum.

Animals↗
PubMed1981

Tumor neutralization by immune in vitro-sensitized splenocytes depends on an interaction with bone-marrow-derived cells.

In a Winn assay, the inhibition of methylcholantherene-induced sarcoma growth by tumor-immune, secondarily in vitro-sensitized splenocytes was augmented by normal unsensitized bone-marrow cells. Bone-marrow cells augmented the effect of a fixed number of sensitized splenocytes in a dose-dependent manner, yet had no tumor-neutralizing capacity by themselves. The marrow's capacity to enhance tumor neutralization was not shared by normal splenocytes, thymocytes or lymph node cells. When two non-cross-reacting tumors were used, marrow cells were capable of augmenting tumor neutralization only if admixed with sensitized splenocytes and the sensitizing neoplasm. Equal numbers of bone-marrow cells administered intravenously to recipients of an admixture of sensitized splenocytes and tumour were unable to augment neutralization, suggesting a direct interaction between sensitized lymphocytes and normal bone-marrow cells in the inhibition of tumor growth.

Animals↗
PubMed1981

Cellular composition of the bone marrow in the chicken: II. The effect of age and the influence of the bursa of Fabricius on the size of cellular compartments.

The blood and bone marrow of New Hampshire chicks were analyzed quantitatively from the time of hatch to 8 weeks of age. Hormonal bursectomy was performed by treating embryonating eggs on the 11th day of incubation with testosterone propionate (TP) which resulted in severe hypogammaglobulinemia and complete atrophy of the bursa of Fabricius. TP-treated birds exhibited some lymphocytopenia, reduced splenic weight, and lack of plasma cells in their bone marrow. The number of cells per milligram bone marrow was comparable in normal and TP-treated birds, falling in the range reported for laboratory rodents. The chick medullary hemopoiesis is characterized by the predominance of erythroblasts throughout early development; granulocytes and lymphocytes represent much smaller cellular compartments than in rodents. In the chick granulocytes tend to decrease after hatch, whereas in rodents they tend to increase. The normal chick shows a temporary increase in marrow lymphocytes after hatch, similar to that observed in some young rodents, but on a much smaller scale. Hormonal bursectomy did not prevent the development of a lymphocyte population in the bone marrow. These cells were fewer in TP-treated birds at hatch and at 4 weeks than in normal birds, but at 8 weeks of age normal and bursectomized chicks had comparable numbers of lymphocytes in their marrow. Although some lymphocytes in avain bone marrow may depend on the bursa of Fabricius for their development, a substantial proportion of bone marrow lymphocytes in the chick are bursa independent. The cell surface phenotype and site of origin of these cells remains to be investigated.

Aging↗
PubMed1981

Myelogenous production and maturation of B lymphocytes in the mouse.

Cells of the B lymphocyte lineage in young adult murine bone marrow were identified and resolved into compartments based on cell size and the expression of the mu heavy chain of IgM in the cytoplasm (cmu) or on the cell surface (smu). The proliferative status, renewal rate, and intercompartmental transit of cells through the defined compartments were determined using established protocols of in vivo tritiated thymidine (3H-TdR) administration, followed by radioautography of bone marrow smears. In addition, we specifically tested whether any of the defined cell compartments were derived from long-lived lymphocytes that are known to enter the marrow. Only large cells immediately incorporated the DNA precursor and both small cmu+ smu- and cmu+ smu+ cells were postmitotic lymphocytes. Large cmu+ smu- cells were found to be a rapid transit compartment in which the last mitosis of B lymphocyte differentiation takes place. All large cmu+ smu- cells divided only once, and both daughter cells entered the postmitotic small cmu+ smu- population. Large cmu+ smu- cells relied for their maintenance entirely on cell input from an Ig- progenitor compartment. Progenitors of cmu+ smu- large cells were not small lymphocytes, proliferated less rapidly than their descendants, and maintained the input of large cmu+ smu- cells for up to 40 hr. Approximately 70% of small cmu+ smu- cells were the immediate division products of large cmu+ smu- cells, whereas the remainder were derived from a precursor with no detectable mu synthesis. Small cmu+ smu+ cells were the maturation products of small cmu+ smu- cells. This conversion appeared to take place at random rather than as a function of postmitotic age. Renewal times for small cmu+ cells without or with detectable smu were calculated to be 48 and 96 hr, respectively. Only the cmu- smu+ compartment included long-lived cells. All other mu+ populations either proliferated or were replaced by newly produced cells. A conspicuous minor population of large smu+ B cells were detected, and the data relating to these were subjected to several interpretations. These observations provide insight into the origin and fate of B lineage precursors in the marrow and suggest a scheme for the terminal stages of B lymphocytes formation that is similar to the myelogenous production of other hemopoietic cells.

Animals↗
PubMed1980

Natural regulatory cells in murine bone marrow: inhibition of in vitro proliferative and cytotoxic responses to alloantigens.

A lymphocyte-enriched fraction of murine bone marrow (BML), obtained by sucrose density fractionation, contains natural regulatory cells that can profoundly suppress the proliferative and cytotoxic response of syngeneic lymph node cells to irradiated alloantigens in a mixed lymphocyte culture (MLC). A close correlation exists between the inhibition of alloantigen-induced proliferation and the generation of cytotoxic effectors. The suppression of proliferation is dependent on the dose of BML added to the cultures but is not due to cell crowding, since red blood cells, thymocytes, and irradiated splenocytes, all syngeneic to the lymph node responders, do not inhibit proliferation to the degree observed with BML. The addition of BML to cultures does not cause the maximum proliferative response to change from the usual day 5 peak, indicating that there is no change in culture kinetics. The release of nonradioactive thymidine by BML cannot explain the suppression. The target of suppression is maximally affected during the first 24 hr of culture, since adding BML to MLC later than this resulted in negligible inhibition of proliferation. Thus, the natural regulatory cell-mediated suppression reflects inhibition of "early" events in the proliferative response to alloantigens.

Animals↗
PubMed1979

Replacement of fatty marrow by active granulocytopoietic bone marrow following transplantation of mammary carcinoma into mice.

The development of granulocytic hemopoiesis in the fatty marrow of metatarsal bones and caudal vertebrae of adult mice was studied in histological sections for up to six weeks following subcutaneous innoculation of granulocytosis inducing mammary carcinoma. The initial events observed were increase and engorgement of fatty marrow sinusoidal vascular beds, accompanied by numerous lymphoid mononuclear cells in the sinusoids and in the stroma. Foci of granulocytopoiesis appeared admixed with lymphoid cells in the stroma and near the endosteum. Hyperplastic granulocytopoiesis eventually predominated in the marrow of these bones as well as the femoral and sternal marrow of tumor bearing mice. The morphological findings suggested the possibility of stem cell and progenitor cell migration into fatty marrow, but activation of dormant stem cells could not be ruled out. The prevalence of granulocytopoiesis in the entire skeletal marrow is of the marrow including lymphocytes, reduced production of the latter would imply serious compromise for the immune system of the tumor bearing animals.

Animals↗
PubMed1978

The effects of vitamin B6 deficiency on the bone marrow of the rat.

Bone marrow from adult rats fed a vitamin B6 deficient diet for two weeks was found to have reduced numbers of neutrophils, erythroid cells and small lymphocytes. The numbers of transitional cells were not reduced. Since the small lymphocyte population in the bone marrow consists of B cells and null cells in approximately the same proportion, it was concluded that both cell types were reduced as a result of the deficiency. A complete recovery in the cellularity of the bone marrow was brought about by returning the vitamin B6 deficient animals to a normal diet for four weeks. Other effects of the two-week vitamin B6 deficient diet included a failure to gain weight, a decrease in thymus weight and a reduction in the numbers of white blood cells in the peripheral blood. All of these defects were corrected after the animals had been fed a normal diet for four weeks.

Animals↗
PubMed1978

Progenitor cells of erythroblasts: an in vitro investigation of erythropoietin-responsive cells of guinea pig bone marrow.

The experiments were designed to test whether or not erythroblast progenitor cell function could be demonstrated in a morphological cell type designated as "transitional cells." Two cell fractions, were obtained from the bone marrow of normal and polycythemic guinea pigs. One fraction (F1) was enriched in transitional cells and contained few, if any, other cell types which could be considered as candidates for erythropoietin responsive cells (ERC). The other fraction (F2) contained undifferentiated blast cells as well as transitional cells. The effect of human urinary erythropoiesis stimulating factors (ESF) on heme synthesis was compared in these two fractions by measuring 59Fe incorporation into heme. ESF was more effective in stimulating heme synthesis in guinea pig bone marrow cells than homologous sera obtained from anemic or hypoxic animals. The majority of ERC sedimented in F2, but the stimulation index was comparable in the two fractions. It was confirmed by radioautography that the ESF response in F1 was due to the generation of proerythroblasts and basophilic erythroblasts that incorporated 55Fe. The generation of these cells in F1 was dependent on the addition of ESF to the cultures, whereas 55Fe-labeled erythroblasts were recovered from cultured of F2 not supplemented with ESF. ESF induced a proportion of transitional cells to incorporate 55Fe in both F1 and F2. Transitional cells were the only cell type in which heme synthesis was dependent on ESF. in other cells of clearly nonerythroid morphology (mononuclear phagocytes and reticular cells), 55Fe incorporation occurred independent of ESF. Although the fractionation procedure employed is unsuitable for the separation of ERC from bone marrow, it permitted the enrichment of transitional cells, a cell type defined by morphology. Radioautography with 55Fe identified a proportion of these cells as ERC in both F1 and F2 fractions of bone marrow obtained from normal and polycythemic guinea pigs. Although there may be other cell types in F2 capable of responding to ESF, the present studies show that some transitional cells function as progenitors of erythroblasts because they respond to ESF by initiation of heme synthesis and by transformation into the earliest recognizable erythroid cells.

Animals↗
PubMed1978

Cell kinetics in the erythroid compartment of guinea pig bone marrow: a model based on 3H-TdR studies.

A model of steady-state erythropoiesis in the guinea pig is described. The model incorporates an unidentified progenitor compartment, as well as compartments representing proerythroblasts, basophilic, polychromatic and orthochromatic cells. A computer representation of the model permits a simulation of the labeling curves obtained in pulse and intermittent labeling regimes. It was found that a reasonable fit to the data can be achieved when the parameters for the various compartments are essentially identical. The results of a preliminary sensitivity analysis, carried out by perturbing the duration of S phase from the best fit value, are reported. The fit achieved to the data supports the hypothesis underlying the model that each compartment corresponds to one generation and that the flux within and between compartments is sequential.

Animals↗
PubMed1978

Differences in lifespan and rate of turnover between phytohaemagglutinin responsive cells of the bone marrow and of peripheral lymphoid organs.

Radioautographic analyses were performed on PHA stimulated cultures of in vivo labelled cells obtained from mice previously injected with 3H-TdR to selectively label either cells with a rapid renewal rate (RR) or a slow renewal rate (SR). ha responsive cells in the bone marrow (BM) were found to be virtually all RR cells, whereas both RR and SR cells from lymph nodes (LN) and spleen (Spl) were stimulated by this mitogen. However, RR cells were proportionately more responsive to PHA than SR cells in all tissues examined. Only one out of 200 BM PHA blasts belonged to the SR subclass, whereas the RR/SR ratio was approximately 1/1 for LN and 2/1 for Spl. Control experiments demonstrated that significant in vitro re-utilization of 3H-TdR from dying cells did not occur in the cultures. These results support a growing body of evidence that BM PHA responsive cells are precursor T-cells which are known to have a rapid turnover rate.

Animals↗
PubMed1977

Phytohemagglutinin-induced differentiation and blastogenesis of precursor T cells from mouse bone marrow.

The cells in mouse bone marrow (BM) capable of responding to phytohemagglutinin (PHA) were shown to be precursor T cells in experiments employing athymic mice, immunofluorescence, and specific lysis of T or B cells with cytotoxic antisera + complement. In contrast, the responses of lymph node (LN) and spleen (Spl) cells to this mitogen were shown by the same techniques to rely upon resident populations of mature T lymphocytes in these peripheral lymphoid organs. Cytolysis of T cells with anti-theta (anti-Thy 1), anti-thymocyte, or anti-brain antisera abolished the PHA responses of LN and Spl, but had no appreciable effect on the BM PHA response. Lysis of B cells with anti-mouse gamma globulin or anti-mouse IgM antisera had no significant effect on either Spl or BM blastogenesis in response to this lectin. Immunofluorescent studies with fluoresceinated anti-brain sera demonstrated acquisition of T-cell surface antigens by BM null lymphocytes during the blastogenic response of this tissue to PHA. The results of these immunofluorescence experiments were reproducible even when marrow obtained from nude mice and pretreated with anti-brain serum plus complement was employed. The implications of these findings with regard to prophylaxis against graft versus host disease in BM transplant recipients are discussed.

Animals↗