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PubMed1987

[The microenvironment of tumor cells and the antitumor effect of hyperthermia].

Intravenous infusion of 20% solution of glucose (80 mg/kg of body mass per 1 min) resulted in considerable changes in microenvironment of tumor cells: by the 90th-120th min of infusion there was a decrease in pH, pO2, blood flow inhibition, an increase in the relative number of cells in the S-phase of the mitotic cycle in a tumor. There was no increase in tumor ATP and glucose up to the values at which these substance could enhance thermoresistance, a situation being rather favorable for realizing a damaging effect of hyperthermia. The use of hyperglycemia in the above regimen prior to MWF-hyperthermia enhanced 2-3 times its antitumor effect on the model of subcutaneously transplanted Guéren carcinoma and Pliss lymphosarcoma. Glucose at the concentration of 5-0 mmol enhanced the thermosensitivity of L-1210 cells. The results indicated the efficacy of hyperglycemia combined with hyperthermia.

Animals↗
PubMedDate not supplied

[Effect of microenvironment on the conformation of m-cholinoreceptors in brain synaptic membranes].

Sensitivity of m-cholinergic receptor of synaptic membranes to SH-reagents (PChMB and NEM) was compared before and after its solubilization with detergents. PChMB blocked specific binding of m-antagonist QNB to both forms of the receptor in equal extent, while NEM was effective only after solubilization. After the membranes modification with butanol or arachidonic acid the membrane-bound receptor became sensitive to NEM. The solubilized receptor lost its ability to allosteric inhibition by acid. It is suggested that the receptor conformation is under the control of the membrane microenvironment.

Allosteric Regulation↗
PubMed1979

Maturation of bursal stem cells within allogeneic or syngeneic bursal microenvironment: acquisition of postbursal maturity.

Differentiation of bursal stem cells in an allogeneic or syngeneic bursal microenvironment was compared. Bursal stem cells were transplanted into CY-treated 4-day-old recipients and permitted to differentiate in these hosts for 6 weeks. Their maturity degree was thereafter assessed by transplanting them into secondary recipients by using morphologic and functional criteria. As the secondary recipients 4-day-old CY-treated or CY-treated and surgically bursectomized chicks were used. The results obtained demonstrate that bursal stem cells develop to mature postbursal cells also within an allogeneic bursa. They also indicate that although the interaction of different lymphoid cells requires histocompatibility, the interaction between stromal cells in the bursa and lymphoid progenitors is not genetically restricted.

Animals↗
PubMed1985

T cell locomotion in the tumor microenvironment. I. A collagen-matrix assay.

Previous studies have shown that lymphocytic infiltrates of different mouse mammary tumors contain different proportions of the T cell subsets Lyt-1+ and Lyt-2+. These characteristic subset ratios may be established, at least in part, by differential locomotion of subsets in response to components of the tumor microenvironment, such as soluble chemotactic and chemokinetic factors, cell and stromal surfaces, oxygen tension, and pH. We describe a new in vitro assay for determining how such microenvironmental variables affect lymphocyte locomotion. Suspended lymph node cells, alone or mixed with other cell types, are sandwiched between two layers of type I collagen gel and bathed in culture medium. A halo of locomotory cells fans out around the flattened droplet. Locomotion requires energy and exogenous protein. After a 24-hr incubation at 37 degrees C, 10% CO2 in air, the cell density of the halo is analyzed optically and the subset ratios are characterized by immunofluorescence staining of the gel sandwich. Under standard culture conditions, the locomotory population is enriched 12% in Thy-1+ cells compared with the bulk population, and the ratio of Lyt-1+ to Lyt-2+ cells is significantly increased. Lymphocyte locomotion is inhibited by 1 microM PGE2, by decreased pH and oxygen tension, and by the presence of normal mammary cells or mammary adenocarcinoma cells. The Lyt-1+:2+ ratio in the locomotory population is not altered by PGE2 but is reduced by acidity and hypoxia. The ratio is also reduced by the presence of mammary cells and cells of one of the mammary adenocarcinoma cell lines tested (168) but not by two others (68H and 410). Our data support the hypothesis that the locomotion of T cell subsets is differentially responsive to the types of microenvironmental conditions that vary among tumors.

Animals↗
PubMed1985

Repopulation of the mouse thymus after sublethal fission neutron irradiation. II. Sequential changes in the thymic microenvironment.

The stromal cells of the thymus of sham-irradiated and sublethal fission neutron-irradiated CBA/H mice were analyzed with immunohistology, using monoclonal antibodies directed to I-A and H-2K antigens as well as specific determinants for cortical and medullary stromal elements. In the control thymuses, I-A expression in the thymus shows a reticular staining pattern in the cortex and a confluent staining pattern in the medulla. In contrast, H-2K expression is mainly confluently located in the medulla. Whole body irradiation with 2.5 Gy fission neutrons reduces within 24 hr the cortex to a rim of vacuolized "nurse cell-like" epithelial cells, largely depleted of lymphoid cells. The localization of I-A antigens changes in the cortex and I-A determinants are no longer associated with or localized on epithelial reticular cells. Medullary stromal cells, however, are more or less unaffected. A high rate of phagocytosis is observed during the first 3 days after irradiation. About 5 days after irradiation, the thymus becomes highly vascularized and lymphoid cells repopulate the cortex. The repopulation of the thymic cortex coincides with the appearance of a bright H-2K expression in the cortex which is associated with both stromal cells as well as lymphoid blasts. During the regeneration of the thymus, the thymic stromal architecture is restored before the expression of cell surface-associated reticular MHC staining patterns. The observed sequential changes in the thymic microenvironment are related to the lymphoid repopulation of the thymus.

Animals↗
PubMed1985

The human thymus microenvironment: heterogeneity detected by monoclonal anti-epithelial cell antibodies.

Monoclonal antibodies were raised against human thymus stromal cells and their specificity for the epithelial component of thymus stroma assessed by double immunofluorescence using anti-keratin antibodies to identify epithelium. Our monoclonal antibodies identify six distinct patterns of epithelial cell antigen expression within the thymus: pan epithelial (antibody IP1); cortex (MR3 and MR6); cortical/medullary junction (IP2); subcapsule and subpopulation of medulla (MR10/MR14); Hassall's corpuscles and adjacent subpopulation of medulla (IP3); Hassall's corpuscles only (MR13/IP4). This heterogeneity of antigen expression suggests that many different epithelial microenvironments exist within the human thymus.

Animals↗
PubMed1985

The effect of hemopoietic microenvironment on splenic suppressor macrophages in congenitally anemic mice of genotype Sl/Sld.

Mechanisms underlying mononuclear phagocyte specialization are being probed by studying suppressor macrophages (M phi) as a reference population in mouse models with impaired blood monocyte formation. Splenic suppressor M phi, defined by PGE-mediated inhibition of Con A-induced T lymphocyte proliferation are induced by the i.p. administration of Corynebacterium parvum (CP). Mice severely depleted of bone marrow and blood monocytes by treatment with 89Sr fail to show this suppressor M phi response to CP, although M phi-forming stem cells, assessed as splenic M-CFC in vitro, are increased 20-fold. These observations suggest that radiosensitive bone marrow stem cells are necessary for the generation of both suppressor M phi and monocytes and that one such stem cell may be common to both types of mononuclear phagocytes. This notion was explored further by employing congenitally anemic mice of the genotype S1/S1d in which the hemopoietic microenvironment is genetically defective and thus unable to support the proliferation, differentiation, and function of stem cells. The congenital defect was found to be additionally expressed in the S1/S1d mouse by a monocytopenia of less than 10% of the values in normal congenic littermate controls and by the failure of splenic M-CFC to increase in response to CP. PGE-producing suppressor M phi expressing Fc gamma 2b receptors, however, were induced by CP in S1/S1d mice with no significant diminution of suppressor activity. These data establish the fact that significant impairment of the formation of monocytes is part of the overall hemopoietic defect in S1/S1d mice. PGE-producing suppressor M phi, however, were inducible at normal functional levels in the presence of a profound monocytopenia, and therefore appear to be independent of the mechanisms that regulate blood monocyte formation. Ablation of the bone marrow with 89Sr resulted in failure of CP to induce suppressor M phi in the spleens of the S1/S1d mice as in the littermate controls. Other observations in the present study, when taken with data from the 89Sr model, show the additional independence of these suppressor M phi from splenic M-CFC. In aggregate, these findings delineate three functionally definable populations of mononuclear phagocytes that appear to be independently regulated.

Anemia, Hemolytic, Congenital↗
PubMed1979

Prolonged hematopoiesis in a primate bone marrow culture system: characteristics of stem cell production and the hematopoietic microenvironment.

Maintenance of myelopoiesis and pluripotential stem cell production for prolonged periods in vitro hitherto has been limited to mouse bone marrow culture. In an effort to adapt the system for use in higher species, particularly in human and non-human primates, studies were undertaken using the prosimian species, Tupaia glis (tree shrew). In a number of experiments the duration of sustained normal hematopoiesis observed in cultures of this species, following a single inoculum of 5 X 10(6)--10(7) bone marrow cells, with or without addition of fresh allogeneic bone marrow exceeded 1 yr. Analysis of suspension cells obtained by weekly demidepopulation of such cultures revealed production of CFU-C, differentiating neutrophils, and basophils at high levels. Direct comparison with murine cultures indicated that in both species a complex series of cellular interactions takes place within an adherent environment of marrow-derived endothelial cells, macrophages, and fat-containing cells. Certain functional and ultrastructural features served to distinguish murine from Tupaia marrow cultures, and the prolonged duration of in vitro hematopoiesis in the latter species could be attributed to a regenerative capacity possessed by its adherent hematopoietic microenvironment. The availability of this primate marrow culture system should facilitate studies of hematopoiesis, viral leukemogenesis, and transplantation biology, which have more direct relevance to man than that provided by the existing murine system.

Animals↗
PubMed1979

[Dependence of the functional activity of immunocompetent mouse spleen cells on their hemopoietic microenvironment].

Accumulation of erythropoietic, granulopoietic cell elements, a change in the ration and absolute count of the T, B cells, and "null" lymphocytes, as well as a sharp inhibition of primary immune response were found in the spleen of CBA mice treated with antierythrocyte sera. The inductive phase of immunogenesis proved to be sensitive to the action of antierythrocyte sera. The data obtained apparently demonstrated the existence of a functional relationship between the immunocompetent spleen cells and their non-lymphoid hemopoietic microenvironment.

Animals↗
PubMed1982

Hematopoietic microenvironment transfer by stromal fibroblasts derived from bone marrow varying in cellularity.

Autologous fibroblast derivatives of red and yellow marrow of rabbits were shown to differ in their capability to transfer a hematopoietic microenvironment upon implantation under the renal capsule. Although a heterotopic ossicle formed in each instance, the quality of the associated medullary tissue mirrored the quality of the bone marrow used to generate the stromal fibroblasts. Thus, fibroblasts cultured from a cellular marrow produced a stroma with numerous hematopoietic foci whereas those cultured from a severely hypocellular marrow produced a stroma with mainly fat cells. The results with 21 implants point to a transmittable regulatory role of a class of stromal fibroblasts.

Animals↗
PubMed1984

IgA antibodies in the bile of rats. IV. Synthesis of secretory antibodies in irradiated rats reconstituted with spleen cells: influence of microenvironment on the regulation of IgA production.

Inbred rats were given sub-lethal doses of irradiation so that they were unable to make antibodies unless they were reconstituted with syngeneic lymphoid cells. The ability of the reconstituted rats to make antibodies of the IgA class was measured in terms of the titres of specific antibodies that appeared in their bile. After syngeneic spleen cells, together with antigen, were injected into the spleens of irradiated rats, the titres of specific antibodies that appeared in the bile were low. After the same dose of spleen cells and antigen had been injected into the GALT of irradiated rats, the titres of biliary antibodies were substantial. These results, together with those of appropriate control experiments, suggest that radio-resistant influences in the microenvironment of the GALT may be important in inducing lymphoid cells to produce antibodies of the IgA class in response to local antigen.

Agglutination Tests↗
PubMed1983

Studies of haemopoietic stem cells and microenvironment in chronic irradiated mice.

Mice were irradiated at a dose rate of 70 rad per day for 25 days. Changes in properties and functions of haemopoietic stem cells and microenvironment were observed through a period of 12 months after termination of continuous irradiation. It was shown that the radiation damage of haemopoietic stem cells played an important role in the radiation-induced damage of haemopoiesis. This was further supported by the fact that transplantation of syngeneic bone marrow cells immediately after termination of continuous irradiation at 70 rad per day for 25 days would greatly improve the haemopoietic function of the irradiated mice, including the total recovery of CFU-S and numbers in the bone marrow and cell counts in the peripheral blood.

Animals↗
PubMedDate not supplied

The microenvironment of human breast with clinical cancer.

The characteristics of the mammary glandular tree have been studied in 100 human breasts removed for clinical cancer by radical mastectomy. The glandular tree was observed in whole thin (2 mm) stained sections under a stereoscopic microscope with removal of any suspicious or interesting change for histology. The results allow to categorize as follows the microenvironments in which mammary neoplasia may clinically appear. In respect to the main characteristics of the collateral glandular tree, clinical breast cancer may occur in: (a) atrophic breasts without lobules or lesions in 17% of cases; (b) atrophic breasts with persistent lobules and minor pathologic changes such as cysts, apocrine metaplasia, sclerosing adenosis, fibroadenoma and ductal hyperplasia in 19% of cases; (c) atrophic breasts with proliferative lobular changes (atypical lobules), duct papillomas, in situ carcinomas and/or microscopic independent foci of infiltrating carcinoma in 31% of cases; (d) adenosic breasts, which are breasts rich in mammary lobules, with the minor pathologic changes specified under (b) in 14% of cases; (e) adenosic breasts with the severe proliferative changes specified under (c) in 17% of cases, and (f) adenosic breasts with normal lobules and without lesions in 2% of cases. Therefore, 83% of the cancerous breasts have normal or pathologic lobules and 81% have lesions of various degrees of severity in the glandular tree.

Adult↗
PubMed1984

A model of intramedullary hematopoietic microenvironments based on stereologic study of the distribution of endocloned marrow colonies.

Hematopoietic colonies were studied in the marrow of alternate fraction-irradiated mice by light microscopic stereology to investigate the microenvironmental organization of marrow. Separate analyses of the relative colony cell density of undifferentiated, granulocytic, erythrocytic, and macrophage colonies in four marrow zones were carried out at 3, 4, and 5 days postirradiation (PI) for all colonies, all periarterial colonies, and all non-periarterial colonies. The results demonstrate a differential colony cell distribution that does not appear to be due to a preferential distribution of certain colony types around arteries. Undifferentiated colony cells showed a consistent predilection for endosteal and periarterial regions, with the majority of colony cells occurring along bone. Erythrocytic colony cells proliferated initially in intermediate and central marrow zones and along arteries. Granulocytic colony cells occurred in all areas at 3 days PI, but increased in density along bone thereafter. Macrophage colony cells occurred in all zones at 4 days PI, but at 5 days were concentrated in subosteal and central regions. Macrophage colonies also occurred periarterially. To explain these findings and the organization of normal bone marrow, we present a detailed model of the microenvironmental organization of intramedullary hematopoiesis. This model portrays the stroma as engendering distinct microenvironments for stem cell replication, stem cell commitment, and early progenitor cell proliferation.

Animals↗
PubMed1984

Establishment of the hematopoietic microenvironment in the marrow of matrix-induced endochondral bone.

Implantation of demineralized diaphyseal bone matrix (DBM) into subcutaneous sites in allogeneic Long-Evans rats results in new endochondral bone formation accompanied by hematopoietic bone marrow differentiation in the newly formed ossicles. In the present study, we investigated the relationship between the time of appearance of hematopoietic stem cells (CFU-S) and those of certain postulated elements of the hematopoietic microenvironment, i.e., fibroblast colony-forming cells (CFC-F), colony-stimulating factors (CSF), and collagen types. CFU-S were first detected at 16 days' postimplantation in the developing ossicle. Their numbers increased exponentially until day 24, decreased slightly between days 27 and 33, and then slowly increased in number again until day 36. CFC-F were present at day 10, and their numbers increased exponentially until day 15, decreased dramatically until day 24, and then remained constant till day 35. Thus, the transient growth of CFC-F preceded the appearance and growth of CFU-S in the ossicle by two or three days.

Animals↗
PubMed1980

The animal enclosure - a microenvironment.

Twelve factors are identified which may be used to describe control criteria for enclosed laboratory animals. The impact of this control can then be evaluated in terms of health and well-being of the animals and laboratory personnel, energy consumption and economics. A review of commonly cited standards and guidelines indicates that they are not explicit regarding required criteria for both the microenvironments and the macroenvironments. However, some data exist which would allow improvement of these standards and which could provide cost effective and energy efficient operations. To expedite these revisions, methods of promulgating voluntary standards are suggested.

Animal Husbandry↗
PubMed1983

The microenvironment of the ovarian follicle.

Observations on the steroid and peptide concentrations and interactions in the microenvironment of the human ovarian follicle have led to an understanding of three important issues in reproductive biology: (1) how the oocyte-granulosa-cell complex matures, (2) how a single follicle is selected and prepared for ovulation and (3) how the events are synchronized so that an ovum ready for fertilization is extruded at ovulation. These findings have clinical significance.

Female↗
PubMed1981

Mouse lymphoid leukemias: symbiotic complexes of neoplastic lymphocytes and their microenvironments.

Of 17 primary lymphoid leukemias of the mouse, 15 symbiotic cell lines were isolated by the explantation of leukemia tissues from which free leukemia cells had been mechanically removed. In vitro survival and growth of symbiotic leukemia cells depended on close association with the adherent cells from the initial explants or other sources. Pseudo-emperipolesis was a remarkable morphologic manifestation of symbiosis common to all cell lines, i.e., the leukemia cells were beneath the adherent cells in close contact. Cell interaction in symbiotic leukemias was studied with a representative symbiotic leukemia AKRL-3 and a cell line B6TE-A from normal thymic epithelium. Failure of the culture supernatant of the adherent cells to support the growth of leukemia cells indicated that the function of the adherent cells was mediated by close cell contact. During the culture, many symbiotic cell lines changed growth patterns and eventually grew independently. Consistent isolation of symbiotic cell lines from most primary leukemias, as well as consideration of the role of the thymus in leukemogenesis, may indicate that the lymphoid leukemias are basically symbiotic complexes of neoplastic lymphocytes and their microenvironments in their natural history. Similar lymphoepithelial cell complexes were isolated recently from normal murine thymus.

Animals↗