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1-19 of 19
Stephen I. Morse
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Journal Articles
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1973) 137 (4): 1078–1090.
Published: 01 April 1973
Abstract
Bordetella pertussis culture fractions produce decreased metabolic responses to isoproterenol and epinephrine in mice and rats, suggesting the possibility of systemic ß adrenergic blockade. The present study was undertaken to elucidate the mechanism of the alteration in adrenergic responsiveness and to clarify its relationship to other biological effects of the organism. Lymphocytes were selected as a suitable tissue because of the marked alteration in lymphocyte distribution in pertussis-treated mice and rats, suggesting a change in the surface properties of these cells. Human peripheral blood lymphocytes, purified by nylon fiber chromatography, were studied. In short incubation experiments (20 min or less) B. pertussis did not alter the cyclic AMP response to isoproterenol, prostaglandin E (PGE 1 ), or methacholine. However, when cells were preincubated with B. pertussis for 90 min at 37°C, the responses to all three agents were markedly inhibited. Although these observations provide direct confirmation of the ability of B. pertussis to inhibit catecholamine responsiveness, the fact that PGE 1 and methacholine responses were also inhibited suggests that blockade at the level of the ß adrenergic receptor is doubtful. The inhibitory activity was localized in a nondialyzable, protein-rich fraction that is precipitated from B. pertussis culture fluid by ammonium sulfate at 90% of saturation. The bulk of the activity was obtained in the load volume after 50,000 g centrifugation in a cesium chloride gradient, density 1.2–1.5 (fraction 4). Fraction 4 produced a change in lymphocyte hormonal responsiveness at concentrations as low as 5 ng/ml. The relationship between cyclic AMP inhibitory activity in isolated human cells and leukocytosis-producing activity in intact mice was studied. The two activities seemed to parallel one another quite closely until the final Sephadex G-150 fractionation step, in which the two activities were obtained in the same column fraction, but a greater recovery of the leukocytosis-producing activity was obtained. Additional purification will be required to establish conclusively whether the same macromolecule is responsible for both activities. The availability of a bacterial product that markedly inhibits cyclic AMP accumulation in purified lymphocytes may help to clarify the role of cyclic AMP in lymphocyte activation by antigen and nonspecific mitogens.
Journal Articles
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1972) 136 (6): 1581–1593.
Published: 01 December 1972
Abstract
The mechanism by which Bordetella pertussis organisms and their products induce lymphocytosis in mice was analyzed in terms of the localization of syngeneic Cr-51-labeled lymph node cells. Labeled lymphoid cells incubated in vitro with the supernatant of B. pertussis cultures and then injected intravenously into normal recipients, or labeled cells injected into pertussis-treated recipients were unable to "home" to lymphoid organs but persisted for long periods in the blood. In animals "equipped" with a population of Cr-51-labeled lymphoid cells, administration of B. pertussis organisms or culture supernatant effected a shift of radioactivity from lymph nodes and spleen into the peripheral blood, coincident with the lymphocytosis. In in vitro experiments it was found that the active principle could bind to both erythrocytes and lymphocytes and could spontaneously elute from these cells onto labeled lymphocytes which were then unable to home efficiently. The data suggest that Bordetella pertussis -induced lymphocytosis involves a reversible attachment of the pertussis factor onto the surfaces of lymphocytes which prevents their recirculation to lymphoid organs. Recirculating lymphocytes are presumably affected as they emerge from lymphoid organs to enter the blood.
Journal Articles
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1970) 132 (4): 663–672.
Published: 01 October 1970
Abstract
Peripheral blood lymphocytes were isolated from normal mice and mice undergoing pertussis-induced lymphocytosis. After labeling in vitro with tritiated uridine the cells were transfused into normal or pertussis-treated mice. It was found that the lymphocytes from pertussis-treated mice entered the lymph nodes of both normal mice and pertussis-treated mice to a significantly lesser extent than did normal lymphocytes which had been transfused into either class of recipient. In addition, an interdependence of changes in the various body compartments examined was found when normal lymphocytes were injected into either type of recipient. However, when pertussis lymphocytes were injected into normal mice there was no interrelationship between the changes in the node with those in the blood, liver, lung, or spleen. In the case of pertussis lymphocytes transfused into pertussis-treated mice no interrelationship between any two compartments was observed. It was concluded that in pertussis-treated mice there is an inhibition of lymphocyte emigration which is primarily the consequence of an effect on the cell.
Journal Articles
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1970) 131 (6): 1342–1357.
Published: 01 June 1970
Abstract
Two distinct particles have been recognized in the extracellular fluid of B. pertussis cultures. Both appeared to arise from the surface (cell wall) of the organism. One of these, a membranous particle, seemed to derive from long projections on the organism composed of the outer membrane of the cell wall. The second particle, a fine filament, was not readily comparable with any previously described bacterial structure. The two particles could be separated from each other by gradient centrifugation in CsCl. Lymphocytosis-promoting factor and histamine-sensitizing activity were only associated with fractions containing the fine filaments.
Journal Articles
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1969) 129 (3): 523–550.
Published: 01 March 1969
Abstract
1. Leukocytosis- and lymphocytosis-stimulating activity was present in fluid cultures of B. pertussis . The activity was found primarily in the culture supernatant fluid. 2. The sequential changes in the leukocyte response were similar to those previously observed following injection of intact bacteria into mice. 3. Activity was destroyed by heat and was diminished, but not abolished, by prolonged treatment with proteolytic enzymes. 4. A water-insoluble fraction of the culture supernatant fluid was isolated which contained virtually all of the activity. The specific activity was more than 100-fold greater than that of the intact bacteria, and injection of microgram quantities produced a response. 5. The distribution of histamine-sensitizing factor followed that of leukocytosis-stimulating activity. In contrast, mouse protective antigen was localized to the bacterial pellet.
Journal Articles
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1967) 125 (4): 619–628.
Published: 01 April 1967
Abstract
The 24 hr volume flow, cell concentration, and total cell output of thoracic duct fluid from mice with pertussis-induced hyperlymphocytosis were markedly reduced when compared with values obtained in normal animals. An increase in the number of circulating lymphocytes occurred in several of the pertussis-treated mice despite the presence of an indwelling thoracic duct cannula. The drainage from such animals also showed a reduced cell concentration and total cell output. It is suggested that lymphocyte recirculation may be minimal in pertussis-induced lymphocytosis, and the evidence obtained also suggests that lymphocytes may enter the blood stream by direct routes during the course of the reaction.
Journal Articles
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1967) 125 (3): 401–408.
Published: 01 March 1967
Abstract
By the use of radioautographic techniques it was shown that the lymphocytosis induced by Bordetella pertussis in mice was not caused by an increased production of lymphocytes but was primarily due to the entry into the circulation of mature cells from tissue pools. The accompanying polymorphonuclear leukocytosis was due to both proliferation of myeloid elements and entry of mature cells from tissue reserves, with the former the predominant mechanism.
Journal Articles
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1967) 125 (1): 45–59.
Published: 01 January 1967
Abstract
1. Multiply resistant strains of Staphylococcus aureus often harbor one or more extrachromosomal drug resistant factors as well as temperate prophages capable of mediating generalized transduction. 2. Spontaneous transduction occurs in mixed cultures of such staphylococcal strains, and the extrachromosomal resistance factors are involved more frequently than are chromosomal genes. 3. Spontaneous transduction of extrachromosomal determinants of erythromycin resistance and of linked penicillin-erythromycin resistance occurs in the kidneys of mice in which mixed infection has been induced.
Journal Articles
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1966) 123 (2): 283–298.
Published: 01 February 1966
Abstract
1. In mice rendered lymphocytopenic by X-irradiation or hydrocortisone acetate, pertussis vaccine evoked both lymphocytosis and polymorphonuclear leukocytosis. 2. When mice with lymphocytosis induced by pertussis vaccine were X-irradiated, prompt and extensive destruction of circulating as well as tissue small lymphocytes occurred. The devitalized circulating cells were cleared from the blood primarily by the Kupffer's cells of the hepatic sinusoids. 3. Hydrocortisone acetate administered to mice with lymphocytosis did not cause acute lymphopenia nor was there any evidence of destruction of circulating small lymphocytes. However, destruction of these cells within lymphoid tissues was apparent. These observations suggested that adrenal cortical hormones are not "lymphocytolytic" with respect to circulating lymphocytes.
Journal Articles
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1965) 121 (1): 39–48.
Published: 01 January 1965
Abstract
Acid mucopolysaccharides have been extracted from whole rabbit polymorphonuclear leucocytes and from the cytoplasmic granules of these cells. The leucocyte acid mucopolysaccharides can be separated into two fractions by the solubility of their CPC complexes in solutions of differing salt concentration. One of these fractions appears to be identical with hyaluronic acid; the other appears to be an atypical chondroitin sulfate. On both a dry weight and total protein basis the polymorphonuclear leucocyte granule contains approximately 2.6 times as much acid mucopolysaccharide as does the whole cell. Hyaluronic acid is concentrated in the granules in particular; its function is unknown. These results do not indicate that all lysosomes contain abundant acid mucopolysaccharides, for no detectable carbohydrate of this class could be extracted from lysosome-rich alveolar macrophages.
Journal Articles
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1965) 121 (1): 49–68.
Published: 01 January 1965
Abstract
1. Intravenous injection into mice of phase I Bordetella pertussis vaccine resulted in a striking hyperleucocytosis with a predominating lymphocytosis. Intraperitoneal inoculation was less effective, and subcutaneous administration was inactive. 2. Active immunization prevented the hyperleucocytosis; passive immunization was less effective. 3. Reticuloendothelial blockage reduced the effect of the vaccine. 4. Extirpation of the spleen or thymus did not alter the leucocyte response. 5. Histologic studies suggested that the increase in circulating lymphocytes resulted from release of cells from lymphoid organs, including the thymus.
Journal Articles
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1963) 117 (1): 19–26.
Published: 01 January 1963
Abstract
An antigen composed of glycerophosphate and glucose has been isolated from the cell walls of a strain of Staphylococcus albus . The antigen reacted with homologous and heterologous S. albus antisera. Similar material was isolated from the cell walls of three other S. albus strains. The antigen did not react with S. aureus antiserum nor with normal human or rabbit serum. The antigen appeared to have a backbone structure of glycerophosphate with appended monoglucoside units. The antigenic determinant was shown to be glucose in alpha linkage.
Journal Articles
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1962) 116 (2): 229–245.
Published: 01 August 1962
Abstract
The cell walls of an 80/81 strain of Staphylococcus aureus (NYH-6) contain alanine, glycine, glutamic acid, lysine, muramic acid, glucosamine, and ribitol phosphate. 94 per cent of the phosphorus and 41 per cent of the glucosamine are removed by extraction of the cell walls with hot 5 per cent TCA, but significant amounts of the other constituents are not extracted by this procedure. The residue after hot TCA extraction (mucopeptide) is susceptible to lysozyme whereas the intact cell walls are resistant. Staphylococcus aureus cell walls are agglutinated by S. aureus antisera. Agglutination of the cell walls of one S. aureus strain is inhibited by absorption of antisera with cell walls of other S. aureus strains but not by absorption with S. albus cell walls. The ribitol teichoic acid can be isolated from cold TCA extracts of the cell walls. This compound consists almost entirely of ribitol phosphate and glucosamine. The isolated teichoic acid of strain NYH-6 is readily fixed to tanned sheep erythrocytes and these sensitized cells are agglutinated by S. aureus antisera. Cold TCA extracts of cell walls of other strains of S. aureus inhibit hemagglutination whereas extracts of S. albus walls do not. Studies on the inhibition of both hemagglutination and precipitation indicate that the antigenic determinant of S. aureus NYH-6 teichoic acid is ß- N -acetylglucosamine.
Journal Articles
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1962) 116 (2): 247–251.
Published: 01 August 1962
Abstract
The cell walls of Staphylococcus aureus are capable of inactivating S. aureus bacteriophage. Furthermore, the cell walls isolated from S. aureus of a given phage type inactivate a variety of different staphylococcal bacteriophages. Under the conditions employed neither the isolated mucopeptide nor teichoic acid components of the cell walls act as bacteriophage receptor.
Journal Articles
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1962) 115 (2): 295–311.
Published: 01 February 1962
Abstract
A technique is described for the isolation and purification of an antigen released into the culture medium by Staphylococcus aureus strain Smith. The antigen was found to be homogeneous when examined by free electrophoresis and analytic ultracentrifugation. Immunologic homogeneity was established by immunoelectrophoresis and quantitative precipitin tests using high titer antiserum prepared against the homologous organism. Chemical analysis showed that the antigen contained 70 per cent carbohydrate, of which approximately 30 to 35 per cent was believed to be glucosamine. The analytic data suggested that another amino sugar, probably carboxylated, was also present, but extreme lability of this compound to mild hydrolytic procedures has thus far precluded further identification. The remainder of the antigen was composed of alanine, glutamic acid, aspartic acid, lysine, glycine, serine, and threonine. No muramic acid was found. The chemical and physical data indicate that the antigen described herein is a previously unrecognized component of Staphylococcus aureus . The purified compound was capable of absorbing agglutinating antibody from antiserum prepared against S. aureus Smith, indicating that it was a surface component of this encapsulated staphylococcus. It is proposed that the antigen be known as the Smith surface antigen (SSA). The injection of SSA into rabbits did not produce precipitating antibodies. However, SSA did precipitate at low concentrations (0.5 µg/ml) with antiserum prepared against S. aureus Smith and one other strain of S. aureus tested. Antiserum against two other aureus strains reacted only with high concentrations of SSA. SSA did not react with S. albus antiserum or with normal sera from several animal species. Experiments are in progress to define further the distribution of SSA. Intradermal injection of small quantities of SSA into rabbits immunized with S. aureus Smith evoked a reaction of cutaneous hypersensitivity, which was maximal in 8 to 12 hours. SSA appeared to be the substance responsible for the ability of S. aureus Smith to resist engulfment by phagocytes, since absorption of Smith antiserum with SSA effectively removed opsonizing antibodies. SSA induced protection in mice against experimental staphylococcal disease. The subcutaneous injection of 0.1 µg resulted in protection against a subsequent intraperitoneal challenge with 50 to 100 LD 50 's of S. aureus Smith suspended in mucin. Increasing as well as decreasing the immunizing dose resulted in significantly less protection.
Journal Articles
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1960) 111 (5): 667–687.
Published: 01 May 1960
Abstract
The phagocytosis and intracellular destruction of bacteria by rabbit polymorphonuclear leucocytes has been studied in vitro under defined conditions. The efficient and continuing ingestion of bacteria was dependent upon ( a ) opsonic factors present in fresh rabbit serum as well as upon, ( b ) the availability of an adequate supply of glucose in the medium. The effects of selected enzymatic inhibitors on the metabolic and functional activities of the leucocytes was investigated. Cyanide which inhibited oxygen consumption had no effect on the ingestion or inactivation of bacteria, Iodoacetate and arsenite which blocked glycolysis produced a marked inhibition in particle ingestion. 2,4-Dinitrophenol which stimulated both oxygen consumption and glycolysis, depressed phagocytosis after a 1 hour latent period. It was concluded that phagocytosis was an energy-requiring process in which glycolysis served as the most important source of energy. Leucocytes which were ingesting heat-killed bacteria exhibited increases in oxygen consumption, glucose utilization, and lactic acid synthesis. The effect of particle ingestion on glycogen metabolism was characterized by an initial period of glycogenolysis followed by an enhanced rate of glycogen synthesis. Leucocytes which had previously ingested heat-killed bacteria also demonstrated increased rates of phagocytosis.
Journal Articles
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1960) 111 (5): 689–704.
Published: 01 May 1960
Abstract
The effects of a purified bacterial lipopolysaccharide endotoxin on homogenous populations of rabbit polymorphonuclear leucocytes have been studied in vitro under defined conditions. Employing a 500-fold range of concentration (0.1 to 50.0 µg./ml.), it was shown that endotoxin enhanced the rate at which staphylococci were killed by leucocytes. The mechanism underlying the increased killing was found to be a direct stimulation of the phagocytic activity of the leucocyte and not mediated by the release of bactericidins or opsonins from the treated cells. In the presence of 10 per cent serum all concentrations of endotoxin enhanced phagocytosis, whereas at lower serum concentrations, the higher doses of lipopolysaccharide inhibited the phagocytic activity of the cells. Similar concentrations of endotoxin were capable of increasing the utilization of glucose and the production of lactic acid. Endotoxin treated leucocytes exhibited no change in oxygen consumption, and only a slight depression in glycogen synthesis. It appeared that endotoxin could interact and alter the functional and metabolic properties of leucocytes in the absence of serum. The demonstration of enhanced phagocytic activity of endotoxin-treated cells was dependent upon the particular opsonic requirements for the organism under study.
Journal Articles
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1959) 110 (3): 419–443.
Published: 01 September 1959
Abstract
A method has been described for the study in vitro of leucocyte-bacteria interactions which permits the simultaneous evaluation of both phagocytosis and intracellular bacterial inactivation. Employing this technique, the fate and localization of staphylococci in homogeneous suspensions of rabbit polymorphonuclear leucocytes have been studied. Coagulase-positive strains of S. aureus were not efficiently ingested in the presence of normal rabbit serum. In contrast, coagulase-negative strains of S. albus were rapidly engulfed and inactivated. Immune sera prepared against a coagulase-positive strain enhanced the the ingestion of the homologous organism as well as of three heterologous strains of S. aureus . Following phagocytosis, prompt intracellular killing of S. aureus occurred. The thermostable opsonins in immune sera reacted only with strains of S. aureus . A comparison between polymorphonuclear leucocytes obtained from normal and immune animals revealed no differences in their ability either to ingest or kill coagulase-positive staphylococci. Studies with other bacterial species are presented to illustrate: ( a ) phagocytosis followed by intracellular inactivation; ( b ) phagocytosis followed by intracellular survival; and ( c ) the absence of phagocytosis.
Journal Articles
Robert J. Glaser, Wilbur A. Thomas, Stephen I. Morse, James E. Darnell, Jr., With the Technical Assistance of Barbara B. Pesch
Journal:
Journal of Experimental Medicine
Journal of Experimental Medicine (1956) 103 (1): 173–188.
Published: 01 January 1956
Abstract
Rabbits subjected to single pharyngeal infections with group A streptococci developed cardiac lesions characterized by myofiber necrosis and a non-granulocytic cellular reaction with histiocytes, lymphocytes, and Anitschkow myocytes. The histopathologic changes were demonstrable in some animals within 24 hours of inoculation, apparently were maximal 72 hours after induction of infection (at which time they were seen in the hearts of all nine rabbits studied), and thereafter healed in the course of the following 2 weeks. The extent of involvement was variable, and with healing the necrotic areas were replaced by fibrous tissue. When intradermal infections with the same organisms were produced in rabbits, cardiac lesions, indistinguishable from those observed in the pharyngeally infected group, appeared in a much smaller number of animals. The hearts of five of six rabbits sacrificed a month or more following the last of a series of streptococcal pharyngeal infections exhibited lesions characterized chiefly by fibrosis, although mononuclear cellular infiltrations were also noted. In these repetitively infected animals the presence of occasional multinucleated giant cells and a few small foci of calcification were features not encountered in the single infection group. In a second series of rabbits sacrificed 3 days after the last of three pharyngeal infections with different strains of streptococci, acute as well as more chronic changes were observed. In none of the lesions in rabbits subjected to single or multiple streptococcal infections were bacteria demonstrable, either in histologic sections or in cultures of myocardial tissue. A large number of control animals was studied concomitantly, and in only one instance was a lesion, considered comparable to those described in the streptococcal series, encountered. The implications of these findings, particularly in terms of the non-suppurative sequelae of streptococcal infections in man, are discussed.