Labor and corporate perspectives on stress reduction in the workplace.
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Biomedical subjects
Publications and source records attributed to J A Singer.
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The ability of an established line of mouse macrophages (IC-21) to ingest red blood cells (RBC) aged in vivo was assessed. RBC populations of increasing age were prepared in mice by serial hypertransfusion, a procedure that inhibits erythropoiesis. Mouse RBC with a mean age of about 58 d (normal RBC life span, 60 d) had a circulating half-life of less than 1 d when transfused into normal mice. IC-21 macrophages ingested the in vivo aged RBC in preference to RBC from normal mice (mean RBC age, 30 d). RBC isolated from mice 10 d after being released from one red blood cell lifespan (60 d) of inhibited erythropoiesis (mean RBC age 5 d) were ingested significantly less than RBC from normal mice. The IC-21 macrophage line used with in vivo aged RBC affords a highly defined model system for identifying the mechanism(s) of macrophage-mediated homeostasis.
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We have examined age-related changes in red cells by employing a serial hypertransfusion protocol to generate populations of in vivo-aged mouse red cells. Studies of these old cells have revealed alterations in membrane components; namely, a conversion of band 4.1b to 4.1a and an increase in the amount of membrane-associated, Triton-insoluble globin. Furthermore, we have found that the erythrocyte does change in density, but only during the earliest stages of its life-span. As the cell continues to age, there is no longer a correlation between age and density.
The interaction of the IC-21 murine macrophage cell line and homologous red blood cells (RBC) was assessed in the absence of exogenous opsonins. These results were used to evaluate this system as a potential model for macrophage-mediated clearance of old or damaged RBC. The binding and ingestion of density-separated and unseparated RBC by IC-21 cells were quantitated in assays that involved both 51Cr-labeled RBC and direct microscopy. The number of unseparated RBC that bound to IC-21 macrophages depended on the number of RBC added. Macrophages phagocytized an appreciable proportion of RBC within 3 hours with the ratio of RBC:macrophage of 10, a point at which the RBC-binding was not rate limiting. The mouse RBC were separated into dense- and less-dense fractions which are presumably enriched for old and young cells, respectively. When these RBC fractions were incubated with the IC-21 macrophage, significantly more of these dense cells were phagocytized. These results show that IC-21 macrophage cell line is a useful model for defining the processes whereby aged or damaged RBC are recognized and removed from circulation by macrophages.
This study examined cardiovascular patterns following happiness, sadness, anger, fear, relaxation, and control imagery in 32 subjects while they were seated and while they exercised. Affective imagery was an effective strategy for inducing reliable patterns of systolic and diastolic blood pressure and heart rate associated with particular emotional states. Anger, rather than fear, produced the greatest overall increases in cardiovascular measures and was distinctly opposite from relaxation. Anger differed from fear and all other conditions in terms of greater increases in diastolic pressure following imagery and greater increases in heart rate and slower recovery of systolic pressure following exercise. Sadness was unique in that systolic pressure and heart rate were virtually as high when subjects were still as when they were actually moving. Furthermore, sadness was the one emotional state that seemed to interfere with the cardiovascular adjustments normally associated with exercise. Implications of these findings for current biobehavioral models of emotion, including the role that specific emotions may play in the pathogenesis and treatment of cardiovascular disease, are considered.
We have attempted to correlate the functional activity of protein 3 with its activity as a receptor for concanavalin A. The concanavalin A agglutination of human erythrocytes is enhanced by adenosine. It varies with time of storage of the blood and is dependent on the concentration of adenosine in the medium. Adenine and/or inosine, which increase cellular ATP, do not substitute for adenosine in enhancing agglutination, and adenosine enhances agglutination of fresh erythrocytes with normal levels of ATP. Thus, it appears that cellular ATP levels are not directly involved in modulation of concanavalin A agglutination by adenosine. Trypsin, which hydrolyzes most of the exposed proteins of the cell surface but does not alter protein 3, enhances concanavalin A agglutination without altering the relative response to the cell to adenosine. Glucose, as well as the glucose transport inhibitors maltose and cellobiose, inhibits agglutination. High concentrations of adenosine reverse the inhibition by glucose and enhance agglutination in the presence of maltose and cellobiose. Treatment of erythrocytes with 4,4'-diisothiocyanostilbene-2,2-disulfonic acid disodium salt, which selectively inhibits the anion transport function of protein 3, substantially inhibits adenosine-supported concanavalin A agglutination. Treatment of erythrocytes with iodoacetate under conditions in which it selectively reacts with glyceraldehyde-3-phosphate dehydrogenase inhibits agglutination. Adenosine protects this dehydrogenase in erythrocytes from inactivation by iodoacetate, over the same concentration range in which it enhances agglutination.
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One hundred forty-four gastric ulcer patients in an inner city hospital were studied retrospectively over a five year period. Emphasis was placed on patient follow-up after discharge. The length of hospitalization and the mortality were higher for the surgical group; however, the recurrence rate was higher in the medically treated group. Almost half the patients were followed for less than six months. Reasons are given for this poor follow-up. The high recurrence rates necessitate close follow-up for a prolonged period.
A 60-year-old white male presenting with a clinical picture of obstructive jaundice was subsequently found to have erythropoietic protoporphyria. The diagnosis was suspected because of a history of life-long photosensitivity and was confirmed by finding high levels of erythrocyte protoporphyrin. Liver biopsy revealed birefringent deposits of protoporphyrin by polarization microscopy accompanied by severe hepatic injury and fibrosis. The patient died rapidly from liver failure, and at autopsy the biliary tree was patent. Despite the autosomal dominant transmission of erythropoietic protoporphyria, we failed to detect any family members with the disease. This report is concluded with a brief discussion of the liver involvement in erythropoietic protoporphyria.
A 61-year-old female presented with a right transudative pleural effusion in the absence of ascites and other stigmata of chronic liver disease. A diagnosis of cirrhosis with a secondary hydrothorax was eventually established; however, ascites could never be demonstrated clinically or radiographically until just before her death, when hypertonic saline was administered for symptomatic hyponatremia. Based on the autopsy finding of a 1-mm hole in the right diaphragm and her clinical course, a mechanism for the production of a cirrhotic pleural effusion in the absence of asictes is proposed.
A white ridge that resembled an inverted snowbank and protruded into the anterior chamber from the region of the internal lips of the cataract incision was visualized gonioscopically during and after cataract operation. Its clinical apearance and course are delineated and documented, and its importance in relation to the formation of postoperative peripheral anterior synechiae, vitreous adhesions, and hyphemas is discussed.
A reproducible quantitative assay for the lectin-mediated agglutination of human erythrocytes, depending on different rates of settling of agglutinated and nonagglutinated erythrocytes, was developed. This assay was used to study the aggregation of human erythrocytes by phytohemagglutinin-P. The aggregation of human erythrocytes by phytohemagglutinin-P was found to depend upon the metabolic state of the cells. Metabolically depleted erythrocytes agglutinated much less readily than did similar cells supplied with adenosine. This was not due to swelling and rigidity of the cells, since erythrocytes in hypotonic solution did not exhibit significantly altered phytohemagglutinin-P agglutination. Metabolically depleted erythrocytes, or erythrocytes from blood stored 8 weeks, lysed and resealed in the presence of ATP, were agglutinated by phytohemagglutinin-P to a much greater extent than control samples without ATP. The presence of Mg2+, either alone or with ATP, had little effect on the agglutinability of the resealed membranes. Low concentrations of Ca2+ (0.2 mM) had little effect on agglutinability, although high Ca2+ (5 mM) inhibited agglutinability of the resealed membranes somewhat. Both metabolically depleted erythrocytes and depleted erythrocytes, previously treated with adenosine, when treated with trypsin released similar amounts of sialic acid. The agglutinability of the trypsinized adenosine-supplemented cells increased more readily than did that of trypsinized metabolically depleted cells. The agglutination of erythrocytes was not affected by cytochalasin B (40 mug/ml). Vinblastine (0.2 mM) caused depleted erythrocytes to agglutinate similarly to adenosine-supplemented erythrocytes, but had no effect on the agglutination of adenosine-supplemented erythrocytes. It is concluded that ATP in the human erythrocyte probably participates in the modulation of phytohemagglutinin-P agglutinability. This is not a consequence of the more rigid membrane known to accompany ATP depletion in the erythrocyte, or of the effect of ATP levels on Ca2+ or Mg2+ content. It appears likely that ATP modulates human erythrocyte phytohemagglutinin-P agglutinability through interaction, direct or indirect, with a membrane-associated component, which might also be sensitivie to vinblastine.
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