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At least 19 recordsLinked to original sources
PubMed1978

Cellular microenvironment in relation to local blood flow.

The investigation was designed to identify microenvironmental factors that might be important in the regulation of local blood flow. Cellular microenvironment in terms of Po2, pH, [K+], [Cl-], [Ca2+] and lactate was measured in rat brain by means of specific microelectrodes. Vascular endothelium was stained in vivo with Thioflavine S. Local blood flow was measured with micro hydrogen electrodes. Some intracellular measurements of pH were made in conjunction with extracellular measurements. The main findings were that local autoregulation responses and blood flow changes in response to imposed hypoxic changes were very rapid (1-1.5 s). Microflow responses to changes in local cell activity were limited to a region not more than 250 micron in diameter. Increased blood flow in acute hypoxia occurred within 1-2 s of the fall in tissue Po2 and was much more rapid than changes in either pH or potassium. Intracellular pH changed within 10 s of the onset of severe hypoxia but in all cases the blood flow followed the Po2 much more closely than any other parameter. It is suggested that changes in capillary endothelium and local membrane transmission may play a part in autoregulatory mechanisms.

Animals↗
PubMed1986

Generation of stable cellular phenotypes in a human malignant cell line conditioned by alterations in the cellular microenvironment.

Microenvironmental conditions may result in phenotypic changes of malignant cells and/or selection of preexisting variants with a growth advantage under the new growth conditions. The present study was initiated to evaluate the stability of changes in crucial cellular attributes as induced in vivo by nonimmunological mechanisms. Expression of major histocompatibility antigens, membrane immunoglobulin, in vitro growth rate, chromosome complement, and modal chromosome number were thus examined in a human B-lymphoma line (RH-L4) prior to and after short-term passage through the peritoneal cavity or spleen of newborn mice. Seven sublines (four from spleen and three from peritoneal cavity) of RH-L4 cells were established after the passage. These lines were found to differ phenotypically from the original line in respect to several or all of the attributes that were studied. These differences were stable for greater than 100 cell generations. Analyses of major histocompatibility complex Class II antigen expression indicated that the modulation of this antigen was independent of the immunological competence of the mice and unrelated to cell cycle-dependent variations. The emergence of the variant sublines seemed not to reflect a microenvironmentally determined selection of minority subpopulation in the original RH-L4 lymphoma line but, instead, induced by the growth conditions in the cellular microenvironment in the mouse. It is suggested that inductive processes may be of importance in the generation of phenotypic diversity within individual tumor cell populations, including the generation of phenotypic variants with high metastatic activity.

Animals↗
PubMed1990

Chondrons from articular cartilage (II): Analysis of the glycosaminoglycans in the cellular microenvironment of isolated canine chondrons.

A chondron rich preparation was isolated from mature canine tibial cartilage using low-speed homogenization techniques. Proteoglycans were extracted from this preparation by exhaustive treatment with 4M guanidine-HCl. A significant proportion of the total proteoglycan, measured as uronic acid, was resistant to extraction and represented 27.9% in intact cartilage chips and 18.6% in the chondron fraction. Histochemical examination of chondrons confirmed that extraction resistant proteoglycans remained within the capsule of the chondron after 4M guanidine-HCl treatment. Electrophoretic analysis of the glycosaminoglycans extracted from intact cartilage chips and the chondron fraction showed approximately equivalent amounts of chondroitin sulphate (79.3%), keratan sulphate (16.3%) and hyaluronic acid (4.3%) present. In contrast, the extraction resistant residue in the chondron fraction was significantly enriched for hyaluronic acid (10.5%, p less than 0.05) but was depleted of chondroitin sulphate (70.9%, p less than 0.05). The major chondroitin sulphate isomer in the resistant fraction was chondroitin 6-sulphate while in the soluble fraction, the quantities of the two isomers were approximately equivalent. Comparison with previously published data suggests a role for minor collagens in the retention of proteoglycans in the cellular microenvironment.

Animals↗
PubMed1988

[Hematopoietic microenvironment: cellular and extracellular matrix elements].

In bone marrow, cellular stroma together with extracellular matrix (EM) provide an adequate microenvironment for the proliferation and differentiation of hemopoietic progenitor cells. In this article we describe studies on the cell characteristics of a main stromal phenotype, a fibroblast-like cell and its ability to produce in vitro EM components. Comparative studies were performed in fibroblast cultures derived from normal and acute lymphoblastic leukemic (ALL) bone marrow. The grow characteristics of fibroblasts from ALL marrow as well as its capacity to synthetize collagen, fibronectin and GAGs are impaired when compared to fibroblast from normal marrow. Thus, in ALL the impaired production of EM biomolecules by a transient damaged population of stromal cells, may contribute to the development of a defective microenvironment for hemopoiesis.

Bone Marrow Cells↗
PubMed1992

Follicular dendritic cells in the alternative antigen transport pathway: microenvironment, cellular events, age and retrovirus related alterations.

Follicular dendritic cells (FDC) are located in lymphoid follicles of secondary lymphoid tissues and play a pivotal role in the initiation and maintenance of the secondary antibody response. FDC are an integral part of the microenvironment of the follicle and function as members of the 'alternative antigen transport pathway.' This pathway consisting of the antigen transport cell-FDC-ICCOSOME-B cell axis, leads to the formation of germinal centers where antibody-forming cell and memory B cell development are initiated through interaction of FDC-retained antigen, B cells and T helper cells. Evidence suggests that these interactions are down-regulated through antibody feedback, or as needed, reactivated with the utilization of FDC-retained antigen for the maintenance of antibody levels. Age- and retrovirus-related FDC defects seriously compromise the capacity of this pathway to maintain immunity.

Aging↗
PubMed1987

Immunoregulation in the Peyer's patch microenvironment. Cellular basis for the enhanced responses by the B cells of X-linked immunodeficient CBA/N mice.

The Peyer's patches (PP) of X-linked immunodeficient (xid) CBA/N and hemizygous (CBA/N X DBA/2)F1 (CDF1) male mice contain a B cell subpopulation that expresses the Lyb-5 maturational marker and is responsive to type 2 and T cell-dependent antigens in vitro, a B cell phenotype which is absent from the spleens of xid mice. Experiments reported here show that xid spleen B cells co-cultured with B cell-depleted PP cells from xid mice differentiated into specific plaque-forming cells in response to trinitrophenyl-Ficoll (type 2) and sheep erythrocytes (T cell-dependent). Two cell types were involved in this normalization of xid B cell responses. An accessory cell activity present in the PP, but not the spleens, of both CDF1 male (xid) and CDF1 female (normal) mice was required for the response to either the type 2 or T cell-dependent antigens. In the presence of this PP accessory cell, T cells from the PP of either xid or normal mice supported responses to both classes of antigens. In contrast, T cells from the spleens of xid mice did not support the response to trinitrophenyl-Ficoll, although the splenic T cells from normal mice did synergize with PP accessory cells in allowing plaque-forming cell development by xid B cells to this type 2 antigen. The xid PP T cell activity required for the type 2 response by xid B cells was present in the Ly-1+, Lyt-2- subpopulation, and the xid PP accessory cell activity was provided by an enriched population of dendritic accessory cells. These results demonstrate the the lymphoreticular cells comprising the PP microenvironment provide effective support for the differentiation of xid B cells in response to type 2 and T cell-dependent antigens.

Animals↗
PubMed1991

Chondrons from articular cartilage. III. Morphologic changes in the cellular microenvironment of chondrons isolated from osteoarthritic cartilage.

Chondrons were isolated from human and canine osteoarthritic cartilage using low-speed homogenization techniques. Changes in chondron morphology were evaluated using differential interference-contrast microscopy, phase-contrast microscopy, and histochemical and ultrastructural methods. Chondrocyte viability was assessed using fluorescein diacetate staining, and chondron metabolism was investigated using autoradiography. The results suggest that initial changes in the collagen and proteoglycan distribution within the chondron are followed by chondrocyte proliferation to form clusters. These techniques offer the potential to study cell matrix interactions in degenerative osteoarthritis.

Aged↗
PubMed1986

Chemosensitivity testing in V79 spheroids: drug delivery and cellular microenvironment.

Chinese hamster V79 multicell spheroids growing in tissue culture exhibit many of the same properties as solid tumors outgrowing their blood supply, including the spontaneous development of both noncycling and hypoxic cell populations expected to be resistant to many chemotherapeutic agents. Cell-sorting techniques were used to select cells as a function of their position (depth) within the spheroid to test this prediction. "Sensitivity profiles" of cells from various regions within spheroids after treatment with doxorubicin, bleomycin, 5-fluorouracil, carmustine, cisplatin, chlorambucil, and mitomycin are presented. Additionally, exposure of preseparated cells was used to distinguish inherent sensitivity from environmental or locational factors. For these drugs, penetration was a problem only for doxorubicin; in contrast, the microenvironment in the intact spheroid had a much greater influence on cell sensitivity.

Animals↗
PubMed1989

Blood flow, metabolism, cellular microenvironment, and growth rate of human tumor xenografts.

Better understanding of the micromilieu of human tumors in situ is mandatory for further improvement of diagnostic and therapeutic interventions. Since investigations of untreated tumors of a wide size range are precluded in humans for ethical reasons, size-dependent changes in the pathophysiology of primary and metastatic human tumors were studied using "tissue-isolated" xenografts in nude rats. Tumor types included lung and breast cancers, ovarian and thyroid carcinomas, uterus tumors, and melanomas. A 10-fold variation in weight-adjusted tumor perfusion indicated large variations in angiogenesis which were unrelated to tumor type. Flow values obtained were consistent with data from clinical observations and were comparable to that in isografted rodent tumors. Using actual consumption and supply rates, maximum oxygen and glucose uptake rates were calculated for each tumor type. The capacity to consume oxygen and glucose varied 9-fold and 4-fold, respectively. However, considering actual consumption rates, blood flow was the principal modulator of substrate supply and tumor metabolism in these human tumor xenografts. Consequently, therapeutically relevant parameters of the metabolic micromilieu largely depended on the efficacy of the tumor circulation. Hereby, high metabolic rates concomitant with high flow values coincided with rapid tumor growth. Thus, in order to design the best individualized therapy, flow-related data should supplement histological classification and clinical staging and grading. Further development of relatively noninvasive technologies (magnetic resonance imaging, magnetic resonance spectroscopy, or positron emission tomography) might permit such monitoring.

Animals↗
PubMed1988

The cellular microenvironment and signaling through cell membranes.

The structural and functional aspects of communication between cells have been reviewed, with emphasis on the cell membrane in detection and transductive coupling of oscillating electromagnetic fields in the pericellular environment. Imposed fields are powerful and highly specific tools in manipulation of the sequence of events in membrane transductive coupling. They have revealed nonlinear and nonequilibrium aspects of these interactions. In cerebral tissue, extracellular fields orders of magnitude weaker than the membrane potential can modulate cell firing patterns, entrain EEG rhythms, alter neurotransmitter release and modulate behavioral states. These sensitivities have also been widely detected in non-neural tissues. It is therefore proposed that an intrinsic communication system between cells based on these weak electromagnetic influences may be a general biological property. A three-step model of transductive coupling is presented. First, a highly cooperative modification of calcium binding occurs in the plane of the membrane surface following a focal event at a receptor site. This "amplifying" stage releases substantially more energy than in the initial events. Cerebral extracellular conductance changes accompanying physiological responses may arise in perineuronal fluid with a substantial macromolecular content and calcium ions may modulate perineuronal conductivity. In the second stage, coupling occurs along transmembrane helical proteins and may be mediated by solitons. The third stage couples transmembrane signals to the cytoskeleton and to intracellular enzyme systems, including membrane-bound adenylate cyclase and the protein kinase system of intracellular messengers. Activation of these intracellular systems is calcium-dependent.

Animals↗
PubMed1987

Role of membrane glycoproteins in mediating trophic responses.

During growth and differentiation the plasma membrane has a key role not only in the reception and transmission of extracellular signals such as hormones and growth factors, but also in communicating cellular response to the cellular microenvironment. Cellular response to trophic stimuli includes alterations of cell shape and cell surface antigenicity, of cell-cell recognition and cellular adhesion, of cell matrix binding and the adaptation of cell surface receptors. The plasma membrane is therefore regarded as a 'central agency' for the integration of a single cell into the complex system of a tissue or of an organism. The numerous functions of the plasma membrane are mainly mediated by membrane integrated glycoproteins or glycolipids both sharing the common feature of covalently bound oligosaccharide side chains. Specific alterations of oligosaccharide structure and metabolism associated with growth, differentiation and various pathologic conditions suggest a specific role for the oligosaccharide moieties in the regulation of cell surface functions (Table 1). This review intends to focus on the role of plasma membrane glycoproteins describing briefly principles of glycoprotein structure and function, and characteristics of their biosynthesis and degradation.

Animals↗
PubMed1991

Cellular pathology of the nerve microenvironment in galactose intoxication.

The effect of chronic hyperglycemia and polyol pathway activation on the Schwann cell has not been resolved although injury to this cell has long been suspected in diabetic neuropathy. Hyperglycemia, resulting from galactose intoxication of four months duration, induces dose-dependent accumulations of endoneurial fluid sodium and chloride that are linked to polyol pathway activity and associated with dose-dependent increases in sciatic nerve water content, endoneurial fluid pressure and (Na+, K+)-ATPase activity. In order to understand the impact of these changes on the nerve microenvironment, cellular elements of the endoneurium were quantitatively and qualitatively assessed in rats receiving 0%, 10%, 20% or 40% galactose diets. After four months of galactose intoxication, dose-dependent changes in the size distribution of myelinated nerve fibers were apparent. A shift in size-frequency histograms of galactose-intoxicated animals towards smaller fibers was accompanied by a decrease in axon diameter and the volume fraction ratio of axon to myelinated nerve fibers. In the sciatic nerve of all 40% galactose-fed rats examined by electron microscopy, Schwann cells of myelinated fibers showed both reactive and degenerative changes. Demyelination was preceded by splitting at the intraperiod line. Remyelination was identified by axons with disproportionately thin myelin sheaths. Axonal dystrophy and degeneration were infrequently seen, but there was axonal regeneration. Dose-dependent increases in mast cell number were observed with degranulation apparent in rats receiving 20% and 40% galactose. Endothelial cell number and basal lamina thickness were increased in the endoneurial vessels of galactose-intoxicated rats. Increased cytoplasmic area and degenerative changes in pericytes were also noted. These observations indicate that significant morphologic changes accompany the hyperosmotic imbalance resulting from galactose intoxication of four months duration. Schwann cell injury and demyelination are present in a disorder linked to polyol metabolism since aldose reductase, the anabolic enzyme of the polyol pathway, is localized to this myelin-forming cell.

Animals↗
PubMed1986

Lymphocyte activation by the Fc region of immunoglobulins.

The Fc region of Ig is required for numerous biological effector functions which include: opsonization, anaphylaxis, C fixation, catabolism of the Ig molecule, FcR binding, and immune regulation. To this latter point, the cellular and subcellular events involved in immune regulation by IC and Fc fragments of Ig have been the focus of numerous investigations. Characterization of cyanogen bromide cleavage fragments from a human IgG1 myeloma protein indicates that one biologically-active site is found in residues 335-357 of the CH3 domain of the molecule. Synthesis of the biologically-active region resulted in a peptide, termed p23, which stimulates mouse and human B cells to secrete polyclonal Ig and activates AA metabolic pathways. In contrast to these findings, p23 is unable to induce B cell proliferation or IL-1 secretion from macrophages. Analysis of data obtained with overlapping peptides, based on p23, suggests that the minimal active sequence needed for B cell differentiation is leu-pro-pro-ser-arg (residues 351-355). In contrast, only p23 or p23 minus the carboxyterminal glu356 and glu357 were able to induce PGE release. Release of biologically-active peptides derived from the Fc region of Ig into the cellular microenvironment may form the nucleus of a nonspecific in vivo immunoregulatory network. The specificity of peptide regulatory activities could reside in their effectiveness at high concentrations in the cellular microenvironment. The interaction of Fc region peptides with receptors on B cells, T cells, and macrophages/monocytes could result in a dynamic control of immune reactivity.

Amino Acid Sequence↗
PubMed1987

ATP as an alternative inhibitor of bacterial and endogenous nucleases and its effect on native chromatin compaction.

The studies reported here demonstrate that ATP may be used in lieu of EDTA to inhibit nuclease digestion of DNA and chromatin. Because ATP is a milder chelator than EDTA and is a biochemical common to the cellular microenvironment in vivo, critical studies of cellular processes that require native structure to be maintained are more feasible without the presence of strong chelators. During the digestion of chromatin into its components by nuclease treatment, ATP assures the retention of nucleoprotein compaction, particularly for large to intermediate-sized oligosomes (2400bp-1000bp in length). ATP used at a concentration of 3.3 mM appears to be somewhat better than EDTA, 1.0 mM, for minimizing degradation of nuclease-treated chromatin. However, termination of nuclease digestion of chromatin and minimization of further degradation by the addition of ATP to a concentration of 1.0 mM was almost equivalent to the addition of EDTA to a concentration of 1.0 mM. Slightly more degradation was observed for the latter condition. In addition, ATP can be used to inhibit endogenous nuclease activity when specific restriction enzymes are needed. Standard low ionic strength DNP, deoxyribonucleoprotein, and DNA electrophoresis of proteinized and deproteinized chromatin oligomers, respectively, indicated that ATP effectively inhibits staphylococcal nuclease. Low ionic strength nucleoprotein electrophoresis to resolve staphylococcal nuclease-digested chromatin indicates that as little as 10(-4) M EDTA can promote structural unfolding resulting in changes in apparent mobilities for chromatin oligomers 250 and 600 bp in length. Comparative digestion of chromatin with staphylococcal nuclease followed by reaction termination by ATP or EDTA showed that this observation was not merely the result of degradation due to inefficiency of ATP enzyme inhibition.

Adenosine Triphosphate↗
PubMed1987

Reed-Sternberg cells and their cell microenvironment in Hodgkin's disease with reference to macrophage-histiocytes and interdigitating reticulum cells.

Fifty-eight paraffin-embedded lymph node biopsies from patients with Hodgkin's disease (36 nodular sclerosis, 14 mixed cellularity, five lymphocyte depletion, and three lymphocyte predominance) were immunostained with a panel of monoclonal (anti-Leu-M1, antileukocyte common antigen) and polyclonal (to lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, and S-100 protein) antibodies by using the avidin-biotin immunoperoxidase technique. Both the immunostaining features of the Reed-Sternberg (R-S) cells and their variants, and the numbers of immunostained accompanying cells morphologically corresponding to macrophage-histiocytes (M-H) and to interdigitating reticulum cells (IRC) were analyzed. Variable numbers of R-S cells and their variants were positive for Leu-M1 in 83% of the cases, for alpha 1-antitrypsin in 40%, for alpha 1-antichymotrypsin in 30%, and for leukocyte common antigen in 3.4%; they were constantly negative for lysozyme and S-100 protein. Whereas the average numbers of accompanying cells immunostained for Leu-M1 were very low, the numbers of S-100-positive IRC were relatively high in all the Hodgkin's subtypes. The average numbers of M-H were lower (P less than 0.1 for lysozyme; P less than 0.001 for alpha 1-antichymotrypsin) in the nodular sclerosis than in the other pooled subtypes. In the nodular sclerosis subtype, however, R-S cells and their variants that stained positive for Leu-M1 appeared to express more frequently the lineage markers of M-H (alpha 1-antitrypsin and/or alpha 1-antichymotrypsin). These data appear to suggest that there is not an apparent qualitative correspondence between the immunostaining features of the cellular microenvironment composed of M-H and IRC and the features of the R-S cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1990

Antigen processing and presentation in vivo: the microenvironment as a crucial factor.

Antigen processing and presentation in vitro is an increasingly well understood phenomenon. However, in vivo, a large number of variables conspire to obscure and confuse. In this article, Nico van Rooijen attempts to bring order to events that occur in the spleen after antigenic challenge: starting with the large body of reliable in vitro data he incorporates information on splenic anatomy, cell trafficking and the cellular microenvironment to arrive at a physiological model for antigen handling in vivo.

Animals↗
PubMed1989

Distribution and activity of antineoplastic drugs in a tumor model.

Antineoplastic drugs can be effective in solid tumors only if they can penetrate several cell layers and retain their activity in the tumor microenvironment. The capacity of several common chemotherapeutic agents to meet these requirements was evaluated in an in vitro tumor model, V79 Chinese hamster cells grown as spheroids. The delivery and toxicity of radioactively labeled 5-fluorouracil, lomustine, tetraplatin, and chlorambucil were determined by use of cell-sorting techniques to select cells as a function of their position (depth) within these spheroids, and the delivery and toxicity of doxorubicin (DOX) were evaluated on the basis of fluorescence intensity. Simultaneous measurement of drug level and toxicity in cells at the time of recovery from different depths within the spheroids led to the conclusion that drug delivery was a problem only for DOX. In contrast, several of the other agents showed a dissociation between cellular drug levels and activity, implicating a major role of the cellular microenvironment in modulating drug toxicity.

Animals↗