A differential responsiveness of in vitro differentiating mononuclear phagocytes from bone marrows of normal and inflamed mice to lymphokines and poly I . poly C.
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Animals↗
Biomedical subjects
R Goldman
Publications and source records attributed to R Goldman.
The regulation of bone marrow-derived mononuclear phagocyte differentiation and mobilization in syngeneic and allogeneic YAC-lymphoma-bearing mice.
YAC-lymphoma inoculation (ip) into syngeneic A/J mice results in a massive in situ proliferation of the lymphoma cells, with non-significant increases in the peritoneal macrophage population, and also in a remarkable and progressive increase in the bone marrow precursor cells forming both macrophage and fibroblastoid colonies in vitro. In the allogeneic situation (BALB/c mice), YAC-lymphoma cells proliferate to a limited extent before tumour regression. These processes (i.e. proliferation and regression) were accompanied by a progressive increase in the peritoneal macrophage population, which declined to normal after tumour regression. Macrophages accumulating at the regression stage exhibited in vitro cytolytic activity towards YAC-lymphoma cells and cytostatic activity towards unrelated cells. No correlation was observed between the limited asynchronous increase in the bone marrow level of precursor cells for in vitro differentiating macrophage and fibroblastoid colonies, on one hand, and macrophage accumulation at the tumour site in BALB/c mice on the other. Conditioned media from in vitro proliferating YAC-lymphoma cells exhibited high colony-stimulating activity for macrophage colony formation in vitro. Bone marrow cells taken from YAC-lymphoma inoculated A/J mice expressed potent tumorogenic potential at early stages after tumour inoculation. At day 2 after tumour inoculation the bone marrow cells were already tumorogenic and concomitantly expressed augmented levels of macrophage and fibroblastoid colony-forming capacity. The results indicate an inter-relationship between tumour growth and mononuclear phagocyte differentiation and proliferation.
Animals↗
Economic survival underlies professional survival which underlies public service.
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Audiology↗
1,25-dihydroxyvitamin D3 and the regulation of macrophage function.
Vitamin D3 deficient (D-) mice show a depressed inflammatory response and both inflammatory peritoneal macrophages and bone marrow polymorphonuclear leukocytes of D- mice exhibit a decreased spontaneous migration under agarose. The impaired phagocytic response of peritoneal macrophages from D- mice can be corrected by incubation with 1,25-dihydroxyvitamin D3 and is not affected by interaction with other vitamin D3 metabolites. Transfer of mice from the D- to the D+ state results in correction of both the inflammatory and the phagocytic response. Intactness of phagocyte function is thus directly dependent on vitamin D3 metabolism.
Animals↗
Ethical confrontations in the incapacitated aged.
Effective factors that have made it possible for an increasing proportion of the population to reach old age have nevertheless presented society with new problems and ethical dilemmas. Several questions that arise include:1) What are the responsibilities of the medical profession in providing medical care or supervision for patients who manifest irreversible decremental processes associated with old age; C); 2) Under what circumstances is there a moral imperative to preserve life, especially in patients who manifest an irreversible loss of awareness or are sustained by purely mechanical means?; 3) What are the limits of the resources which can be allocated to health care in general, and to the aged in particular, in a society in which resources are no longer infinite and allocations may become necessary; C0 4) what is the profession's responsibility for identifying decremental aging changes and characterizing them, even it this information is personally threatening and socially disturbing to those who would prefer to consider them diseases, and thus reversible by traditional means?; and 5) Is there a moral mandate to identify mechanisms of aging and techniques for slowing the process, in order to prolong life beyond what appears to be the normal biologic limit of three generations?
Aged↗
Isolation of glutathione from bovine thymus and its significance to research relevant to immune systems.
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Animals↗
Enhancement of phagocytosis - a newly found activity of substance P residing in its N-terminal tetrapeptide sequence.
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Animals↗
Functional tuftsin binding sites on macrophage-like tumor line P388D1 and on bone marrow cells differentiated in vitro into mononuclear phagocytes.
Mouse bone marrow cells, differentiated in vitro into mononuclear phagocytes (BMDMP), posess functional tuftsin binding sites, i.e. both tuftsin binding capacity and augmented phagocytic response related to tuftsin binding. The binding capacity of BMDMP was shown to be higher by a factor of about three than that exhibited by mouse monocytes and by normal, thioglycollate and Corynebacterium parvum induced peritoneal macrophages. The relatively high binding capacity did not depend on experimental variations in the in vitro culture of these populations (i.e. length of in vitro cultivation, source of serum or presence of conditioned medium leading to cell proliferation). The macrophage-like line, P388D1, was also shown to possess functional tuftsin binding sites and its binding capacity was comparable to that of the peritoneal macrophage populations.
Animals↗
On the mechanism of action of the phagocytosis-stimulating peptide tuftsin.
Incubation of human polymorphonuclear leukocytes (PMNL) or thioglycollate-stimulated mouse peritoneal macrophages with the phagocytosis-stimulating peptide, tuftsin (2.5 X 10(-7) M, at 37 degrees C), caused an increase of 80-90% in intracellular cGMP levels, accompanied by a decrease of 20-25% in intracellular cAMP levels. Significant changes in cyclic nucleotide levels were detectable after 4 min of incubation, were maximal at 10-20 min and persisted for at least 60 min. The concentration dependences of the stimulatory effect of tuftsin on modulation on intracellular levels of cyclic nucleotides and on phagocytosis are similar, suggesting a cause and effect relationship between the two phenomena. This notion is further supported by the finding that 8-Br-cGMP and 8-Br-cAMP elicit stimulatory and inhibitory effects on macrophage phagocytosis, respectively. Measurement of 45Ca2+ influx into PMNL and macrophages in the presence and absence of tuftsin did not reveal any change in 45Ca2+ uptake from the media. However, tuftsin did enhance release of 45Ca2+ from cells preloaded with the isotope. Results suggest that modulation of both the amount of cell-associated 45Ca2+ and the intracellular levels of cyclic nucleotides are key steps in the mechanism by which tuftsin augments phagocytosis.
Animals↗
The effects of phonetic context on speech-sound discrimination.
This study was designed to examine the influence of contextual elements on speech-sound discrimination performance. The test employed was comprised of ten stimulus words located within three sentence structures providing initial, medial, and final placement of stimuli within sentences. All sentence items were presented in two forms, naturally articulated and mechanically assembled, to 25 normal preschool children. Disruption of the suprasegmental feature of the assembled test was achieved by splicing isolated words into sentences previously recorded with silence in the stimulus word position. Statistical analysis indicated that error scores on the assembled sentence items were significantly greater. Disruption of suprasegmental features appeared to significantly influence the discrimination of target sounds within stimulus words when the words were in the medial and final positions of the sentences.
Child, Preschool↗
Mannose-binding activity of Escherichia coli: a determinant of attachment and ingestion of the bacteria by macrophages.
Recently, it was suggested that a mannose-specific lectin on the bacterial cell surface is responsible for the recognition by phagocytic cells of certain nonopsonized Escherichia coli strains. In this study we assessed the interaction of two strains of E. coli at different phases of growth with a monolayer of mouse peritoneal macrophages and developed a direct method with [(14)C]mannan to quantitate the bacterial mannose-binding activity. Normal-sized bacteria were obtained from logarithmic and stationary phases of growth. Nonseptated filamentous cells were formed by growing the organisms in the presence of cephalexin or at a restrictive temperature. Attachment to macrophages of all bacterial forms was inhibited by methyl alpha-d-mannoside and mannan but not by other sugars tested. The attachment of stationary phase and filamentous bacteria to macrophages, as well as their mannose-binding activity, was similar, whereas in the exponential-phase bacteria they were markedly reduced. The results show a linear relation between the two parameters (R = 0.98, P < 0.001). The internalization of the filamentous cells attached to macrophages during 45 min of incubation was much less efficient (20%) compared to that of exponential-phase, stationary-phase, or antibody-coated filamentous bacteria (90%). The results indicate that the mannose-binding activity of E. coli determines the recognition of the organisms by phagocytes. They further suggest that administration of beta-lactam antibiotics may impair elimination of certain pathogenic bacteria by inducing the formation of filaments which are inefficiently internalized by the host's phagocytic cells.
Animals↗
Effects of hypokalemia on the cardiotropic actions of digoxin in dogs. Correlation with inhibition of cardiac Na+,K+-adenosine triphosphatase.
Hypokalemia potentiated the arryhthmogenic effects of digoxin and promoted inhibition of cardiac Na+,K+-ATPase. Acute hypokalemia did not modify digoxin-induced inotropy and therefore altered the quantitative relationship between inhibition of Na+,K+-ATPase and positive inotropy. Chronic hypokalemia impaired the positive inotropic response to digoxin and to isoproterenol in the absence of an electron microscopically detectable cardiomyopathy.
Acute Disease↗
Radiosensitive, thymic hormone-sensitive peripheral blood suppressor cell activity in cancer patients.
Suppressor cell activity which was radiosensitive in most subjects and thymic hormone sensitive in some was identified in patients with cancer, and compared to simultaneously studied normal controls. Suppressor cell activity was measured in cocultures of normal lymphocytes with patient lymphocytes added in microwells using the blastogenic response to phytohemagglutinin and concanavalin A as the measure of activity. Thirty-five patients (lung cancer, 21; leukemia in remission, seven; and various solid tumors, seven) and an equal number of controls were studied. Suppressor cell activity was identified in 71% of the patients. In approximately 75% of these, the suppressor cell activity was radiosensitive (4000 to 6000 rads). For the phytohemagglutinin response, suppressor cell activity was thymic hormone sensitive in approximately 40% (Thymosin Fraction 5 or thymic humoral factor), and for the concanavalin A response, it was thymic hormone sensitive in about 25% of the cases. There was a significant correlation between the presence of immunodeficiency (defined as a phytohemagglutinin response < 35,000 or a concanavalin A response < 12,000 cpm) and the presence of the suppressor cell activity. The suppressor cell activity was heterogenous relative to its radiosensitivity and thymic hormone sensitivity. Suppressor cell activity was observed in all the patient categories. These results indicate that certain available therapeutic manipulations may have significant effects on suppressor cell activity and should be an important subject for further investigation.
Antineoplastic Agents↗
Contrasting effects of activated and nonactivated macrophages and macrophages from tumor-bearing mice on tumor growth in vivo.
The effect of macrophages from normal and tumor-bearing mice on tumor growth was investigated with the use of an in vivo neutralization test. Macrophages from unstimulated and thioglycollate-stimulated peritoneal cavities (nonactivated macrophages) of normal mice enhanced growth of various syngeneic tumors [a 3-methylcholanthrene-induced transplantable fibrosarcoma from inbred C3HeB mice, a spontaneously originated transplantable melanoma (B16) from inbred C57BL/6 mice, and a radiation-induced lymphoma from inbred BALB/c mice]. This enhancing effect was not destroyed by irradiation of macrophages and was apparently mediated by macrophage secretory products. The effect appeared to be unrelated to immunosuppression and may have reflected direct stimulation of tumor cells. In contrast, Corynebacterium parvum-activated macrophages markedly inhibited tumor growth. Peritoneal macrophages from fibrosarcoma-bearing mice, which possessed tumor-inhibitory T-lymphocytes, enhanced tumor growth and abolished the effects of the tumor-inhibitory lymphocytes. Clearly, under certain conditions nonactivated macrophages interfered with the mechanisms of T-cell-mediated antitumor resistance in tumor-bearing mice.
Animals↗
Complement and Fc receptor-mediated phagocytosis of normal and stimulated mouse peritoneal macrophages.
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Animals↗
Tuftsin-macrophage interaction: specific binding and augmentation of phagocytosis.
The binding of [3H]tuftsin to normal and in vivo stimulated mouse peritoneal macrophage populations was studied at 22 degrees C. The [3H]tuftsin binding to thioglycollate-stimulated macrophages was shown to be rapid and saturable, with an equilibrium dissociation constant (K(D)) (calculated from a Scatchard plot) of 5.3 X 10(-8) M. The calculated number of binding sites per macrophage amounts to approximately 72,000. Binding competition studies with unlabelled tuftsin yielded a K(D) of 5.0 X 10(-8) M. [3H] [N-Acetyl-Thr1]tuftsin, an inactive analog of tuftsin, failed to bind specifically to thioglycollate-stimulated macrophages. [N-Acetyl-Thr1]tuftsin and the tripeptide [Des-Arg4]tuftsin failed to compete for tuftsin binding sites, while [D-Arg4]tuftsin, an analog with small tuftsin-like activity, exhibited a low degree of inhibition of [3H]tuftsin binding. Thus a rather high degree of specificity is involved in the binding of the tetrapeptide. Normal as well as six different macrophage populations induced by stimulation with thioglycollate, concanavalin-A, starch, mineral oil, glucan and Bacillus Calmette Guerrin (BCG), exhibited a similar degree of binding of [3H]tuftsin. Corynebacterium parvum (CP)-stimulated macrophages, on the other hand, showed a 6- to 10-fold-lower capacity for tuftsin binding. Under similar experimental conditions, mouse fibroblast and lymphocyte preparations revealed no detectable specific binding. Tuftsin augmented the phagocytic response of normal and stimulated macrophages assessed both for phagocytosis mediated via the Fc-receptor and via non-specific receptors. CP-stimulated macrophages did not exhibit an increased phagocytic response upon treatment with tuftsin.
Animals↗
Functional similarity and diversity in peritoneal macrophage populations induced in vivo by various stimuli.
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Acid Phosphatase↗
The peritoneal absorption of insulin in diabetic man: a potential site for a mechanical insulin delivery system.
The potential of the peritoneum as a site for an "artificial beta cell" was studied. Three 14-hr studies were performed in an insulin-dependent diabetic male maintained on chronic peritoneal dialysis. All studies were performed between dialyses and throughout three standard American Diabetes Association (ADA) 600 calorie meals. The degree of insulin absorption from the peritoneal space was assessed by measuring the changes in plasma-free insulin concentration during these studies. The results of this study demonstrate that normalization of plasma insulin profiles may be observed with the administration of insulin into the peritoneal space. This absorbed insulin exerts hypoglycemic activity that suppresses the meal-induced rise in plasma glucose concentration. Thus, the peritoneal space may be a feasible route into which insulin may be delivered by an artificial beta cell.
Absorption↗