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C M Jones

Publications and source records attributed to C M Jones.

At least 127 records · Page 7Linked to original sources

Role of bacterial lipopolysaccharide and lymphokine in the regulation of macrophage activation: correlates between secretion of plasminogen activator and tumor lysis.

The effects of bacterial lipopolysaccharide (LPS) and lymphokine (LK) upon the activation of murine C57BL/6 peritoneal macrophages (M phi) were studied. Enhancement of the secretion of plasminogen activator (PA) by lymphokine did not require, nor was significantly boosted by LPS. In contrast, lysis of tumor target cells required LPS in addition to lymphokine confirming prior studies (1-3). Once macrophages were induced to secrete PA, LPS suppressed its release but did not directly interfere with fibrinolysis. These findings are consistent with the concept that induction of PA secretion may represent an earlier step in activation than the acquisition of cytolytic potential (4, 5) and that LPS is important both in the regulation of macrophage proteases and mediation of tumor cell lysis (2, 6).

Animals↗

Subhourly variability of circulating norepinephrine and epinephrine in the pregnant ewe and fetal and newborn lamb.

Circulating norepinephrine and epinephrine were determined nine times over a 1-hour period in chronically instrumented ewes (n = 4), their fetuses (n = 4), and lambs (n = 4). In an apparent resting state, assessed by subjective and biophysical parameters, marked fluctuations were demonstrated in the mean norepinephrine and epinephrine values between animals and in the range of the concentrations of each individual animal. The significance of the fluctuations in resting plasma norepinephrine and epinephrine concentrations is discussed.

Animals↗

A vasopressin antagonist blocks the norepinephrine and epinephrine responses to hemorrhage in the fetus.

In 8 chronically cannulated fetal lambs between 119 and 127 days gestation the resting plasma norepinephrine concentration was 528 +/- 77 pg X ml-1 and the resting plasma epinephrine concentration 159 +/- 42 pg X ml-1. Hemorrhage of 20% of estimated blood volume at 2% per min produced a 2.1-fold increase in plasma norepinephrine levels and a 3.4-fold increase in plasma epinephrine levels when the animals were pretreated with an injection of saline (1 ml). Plasma catecholamine levels returned toward control values following return of the shed blood. In contrast, hemorrhage of these animals following pretreatment with an antagonist of the pressor effect of vasopressin did not cause an increase in fetal plasma catecholamine levels. Thus, vasopressin may mediate the sympathetic responses to volume depletion in the fetus.

Animals↗

Macrophage cell lines behave as activated macrophages in the production and regulation of plasminogen activator.

Seven macrophagelike cell lines, WEHI-3, J774, RAW264, FC-1, P388D-1, PU5-R, and PU5-1.8, commonly used as in vitro models of macrophage function, were studied for their fibrinolytic activity in the presence and absence of purified plasminogen. All cell lines, as well as the freshly harvested peritoneal macrophages, produced plasminogen activator, as indicated by the levels of fibrinolytic activity in the presence of plasminogen. However, fibrinolytic proteolysis was most efficiently measured by direct attachment to 125I-fibrin plates, a method which measures both secreted and cell-membrane-associated plasminogen activator. Other non-plasminogen-dependent fibrinolytic activities were also produced by all cells studied and secreted by WEHI-3, FC-1, RAW-264, and thioglycollate-elicited macrophages. Activation of the thioglycollate-elicited macrophages with macrophage activation factor (MAF) induced threefold higher levels of plasminogen activator production but MAF treatment had no effect on the level of activity produced by macrophagelike cell lines. Indeed, the macrophagelike cell lines produced plasminogen activator at levels seen with MAF-activated thioglycollate-elicited macrophages. We conclude that these cell lines constitutively produce activators of plasminogen and, in their failure to respond to MAF, behave as activated macrophages.

Animals↗

The effect of labor on maternal and fetal circulating catecholamines.

Maternal circulating catecholamines were determined in nonpregnant (n = 15) and antepartum (n = 15) subjects and at spontaneous vaginal (n = 20) and repeat cesarean section (n = 20) deliveries. Newborn levels of catecholamines were determined prior to the onset of respiration in the vaginal delivery (n = 20) and cesarean section (n = 20) groups. Maternal levels of norepinephrine at 36 to 38 weeks' gestation were lower than values in nonpregnant individuals, and did not increase at cesarean section but rose to nonpregnant levels at vaginal delivery. Antepartum levels of epinephrine were lower than levels in nonpregnant subjects and rose above nonpregnant levels in both delivery groups (P less than 0.02). Maternal levels of dopamine followed a similar pregnancy decline and rose above nonpregnant levels at delivery in both groups (P less than 0.02). Maternal levels of dopamine in the cesarean section group were significantly higher than those in vaginal delivery (P less than 0.05). Newborn levels of catecholamines demonstrated significant newborn secretion of norepinephrine, epinephrine, and dopamine at delivery in both groups. Umbilical arterial levels of norepinephrine and epinephrine were significantly greater after vaginal delivery than those after abdominal delivery (P less than 0.01). The significance of circulating catecholamines to, and their possible roles in, the parturient women and fetus are discussed.

Catecholamines↗

On the lysis of paroxysmal nocturnal hemoglobinuria erythrocytes by complement: dual role of C3b.

The efficiency of cytolysis by the terminal complement proteins C5b-9 can be markedly enhanced by C3b molecules bound on the target cell membrane (Hammer et al. 1976). This enhancement was shown to be proportional to the number of C3b molecules on the cell membrane. The present experiments have shown that the hemolytic efficiency of the complement membrane attack system is two to five times greater on paroxysmal nocturnal hemoglobulinuria erythrocytes (PNHE) than on normal human E. This difference is attribute to a derivative of C3, probably C3b, on PNHE since it was abolished by anti-C3 but not by anti-C2. The efficiency of C5b-9 to lyse PNHE was only partially decreased by C3b inactivator and beta 1 H, indicating that the C3b on PNHE is not readily inactivated by its regulatory proteins. Furthermore, cells from a single severely affected patient consumed 3-fold more C5b6 than normal human E yet concommitantly measured membrane fluidity was normal. From these observations we conclude that cell-bound C3b on PNHE serves two functions: (a) it increases the hemolytic efficiency of membrane attack components of the complement system; and (b) it provides sites for assembly of the alternative pathway convertases.

Complement C3b↗

Slow reacting substances (leukotrienes): enzymes involved in their biosynthesis.

Slow reacting substances (leukotrienes C4, D4, E4) are synthesized in vivo by a combination of two previously unrelated pathways: lipoxygenase oxygenation of arachidonic acid and the glutathione detoxification pathway. Enzymes involved in the latter pathway (glutathione transferase [RX: glutathione R-transferase, EC 2.5.1.18]; gamma-glutamyltransferase [(5-glutamyl)-peptide: amino acid 5-glutamyltransferase, EC 2.3.2.2] ) have been investigated in guinea pig lung and rat basophilic leukemia (RBL-1) cells. We report data on levels of enzymic activity both before and during the release of slow reacting substances. Both glutathione transferase and gamma-glutamyltransferase are present in significant quantities in guinea pig lung and RBL-1 cells. A model for the changes in gamma-glutamyltransferase during leukotriene release is proposed for the cell line, and differences from the guinea pig lung system are reported. Leukotriene C4 is converted to the more potent leukotriene D4 by the action of gamma-glutamyltransferase on guinea pig ileum during bioassay. gamma-Glutamyltransferase may represent a control feature in the biosynthesis of leukotriene D4, and thus be involved in leukotriene-induced bronchoconstriction in the lung.

Animals↗

Interferon activates macrophages to produce plasminogen activator.

Macrophages and monocytes become activated, by a variety of mechanisms, to exhibit cytotoxicity. Associated with this activation for cytotoxicity is the production of certain neutral proteases, especially plasminogen activator (PA), which may be involved in the mechanism of cytolysis. Supernatants from concanavalin A (Con A) or antigen-stimulated spleen cells contain factor(s) which render macrophages and monocytes activated in vitro (MAF/MIF). We have found that in addition to such spleen cell supernatants murine interferon was able to activate peptone-induced C57BL/6 peritoneal macrophages to produce PA but had no effect on human monocytes. Similarly, human recombinant interferon activated human monocytes but not murine macrophages to produce PA. In addition to displaying this species specificity, interferon was able to function as a monocyte/macrophage activator in this system just as in cytotoxicity and may be a regulator of monocyte/macrophage function in vivo by modulation of proteolytic enzymes.

Animals↗

The effect of hemoglobin F-Chesapeake (alpha 2 92 Arg. leads to Leu gamma 2) on fetal oxygen affinity and erythropoiesis.

A carrier of hemoglobin Chesapeake, born of a normal mother, had a cord-blood hematocrit of 60%. The oxygen affinity of his blood was increased. Hemoglobin F-Chesapeake (alpha 2 Ches gamma 2), partially purified from the infant's blood, had oxygen affinity greater than that of hemoglobin A, but less than that of the adult form of the abnormal hemoglobin (alpha 2 Ches beta 2). These findings suggest that the conformation of that part of the gamma chain which contacts the site of amino acid substitution in Hb F-Chesapeake is similar to the analogous region of hemoglobin F. They also support the hypothesis that regulation of erythropoiesis in late fetal life is similar to that of the adult, and is under fetal control.

Erythropoiesis↗