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R Keller

Publications and source records attributed to R Keller.

At least 199 records · Page 11Linked to original sources
PubMed1990

[Acute effects of the natural atmospheric ozone exposure on lung function of clinically normal smokers and non-smokers].

The influence of moderate ambient ozone exposure on spirometric lung function and bronchial responsiveness was analyzed in 13 healthy adult nonsmokers and 11 asymptomatic smokers. The study was divided into an initial investigation at low atmospheric ozone concentrations of about 80 (range 68-102) micrograms/m3 and a subsequent similar testing at moderately elevated ozone concentrations above 140 (range 145-205) micrograms/m3. Overall there was a slight but significant impairment in forced expiratory volumes (p less than 0.002) at elevated compared with low ozone concentrations. Furthermore, a significant increase in bronchial responsiveness was shown, with a decrease in threshold dose for inhaled metacholine to produce a 50% fall in specific airway conductance (p less than 0.02). In both smokers and nonsmokers there was a similar change in lung function at ambient ozone concentrations, with more pronounced bronchial irritation in the smokers group. It is concluded that even moderately elevated ambient ozone concentrations can induce slight but significant ventilatory obstruction and an obvious increase in bronchial responsiveness in healthy adults. Although the minor impairment of lung function did not cause manifest acute respiratory problems, it still reduced maximal physical ventilation capacity. The results further support the assumption that air pollution may act as a primary trigger in the development of obstructive airway disease.

Airway Obstruction↗
PubMed1990

Mechanisms of macrophage-mediated tumor cell killing: a comparative analysis of the roles of reactive nitrogen intermediates and tumor necrosis factor.

The roles of tumor necrosis factor (TNF alpha) and reactive nitrogen intermediates (RNI) as effectors of macrophage-mediated tumor cell killing were investigated in a variety of tumor cell lines. Three TNF alpha-sensitive tumor targets were also susceptible to resting bone-marrow-derived mononuclear phagocytes (BMMP). This macrophage lytic activity was markedly diminished or even abolished by anti-TNF alpha, indicating that TNF alpha is the major effector of macrophage-mediated killing of these targets. The other 21 tumor cell lines examined were resistant to TNF alpha but, in their large majority, were more or less susceptible to killing by interferon gamma (IFN gamma)- and Corynebacterium parvum (CP)-activated BMMP. Among the various analogues of L-arginine used to assess the role of L-arginine-derived RNI as mediators of macrophage tumoricidal activity, NG-monomethyl-L-arginine (NMMA) was most efficient in suppressing RNI secretion by activated macrophages. In some macrophage tumor-cell combinations, NMMA inhibited both the generation of RNI and the expression of tumoricidal activity in a dose-dependent manner, suggesting a central role for RNI as effectors. In other combinations, NMMA in concentrations that abolished secretion of RNI either affected tumor-cell killing only after its induction by IFN gamma, or not at all. The findings not only support the thesis that macrophages posses various means of coping with tumor cells but also suggest that the mechanism becoming operative is determined predominantly by the pathway of macrophage activation and the properties of the tumor-cell type.

Animals↗
PubMed1990

Resistance to a non-immunogenic tumor, induced by Corynebacterium parvum or Listeria monocytogenes, is abrogated by anti-interferon gamma.

The complex processes that determine the outcome of the interaction of tumor and host were explored in the operationally simple and reproducible rat D-12 ascites tumor model. Animals exhibit weak spontaneous resistance against this tumor that is not augmented by repeated inoculation, by various routes, of irradiated syngeneic D-12 tumor cells, but considerably enhanced after local administration of heat-killed Corynebacterium parvum (CP) or Listeria monocytogenes (LM) organisms. Inoculation of conventional or monoclonal anti-rat IFN gamma antibodies into the same compartment did not affect spontaneous tumor resistance, but largely abrogated the tumor-protective effect triggered by CP or LM. Our findings support the concept that IFN gamma, produced by T cells in the course of the specific immune response raised against immunogenic micro-organisms, is able to enhance and to maintain local tumor resistance and thus to strengthen the capacity of the host to cope with a non-immunogenic tumor.

Animals↗
PubMed1990

MHC class-I antigen deficiency, malignancy and susceptibility of P815 mastocytoma to NK and macrophage killing.

A subline of the murine P815 mastocytoma passaged for a long period of time in histoincompatible hosts was found to be deficient in surface MHC class-I antigens by serological and biochemical methods. In agreement with the lack of restriction elements, this variant cell line was no longer susceptible to killing by cytotoxic T cells stimulated by and directed against the parental tumor cell line in syngeneic DBA-2 hosts. We did not observe the appearance of susceptibility to NK killing concomitantly with H-2 loss. We thus could not confirm the hypothesis of a regulatory function of H-2 structures in NK recognition/killing. Both cell lines were also resistant to lysis by mouse macrophages. The parental cell line was sensitive to rat macrophage killing, whereas the variant line had lost such sensitivity. In spite of resistance in vitro to various defense mechanisms, the variant H-2 loss tumor cell line was less tumorigenic in syngeneic hosts and exhibited a lower metastatic capacity than the parental cell line. We propose that in the H-2 loss subline, survival of cells in vivo is impeded since positive signals mediated by H-2 structures are missing, which are necessary for cell-cell contact and survival.

Animals↗
PubMed1990

Copper in silicon.

Explore the source record for details and available documents.

Journal Article↗
PubMed1990

L-arginine-dependent reactive nitrogen intermediates as mediators of tumor cell killing by activated macrophages.

The capacities of lymphokines and of various microbes to induce in a pure population of bone marrow-derived mononuclear phagocytes tumoricidal activity and/or the production of L-arginine-dependent reactive nitrogen intermediates, measured by the release of nitrite, were comparatively assessed. These parameters were found to be closely correlated in a variety of experimental situations, i.e., enhanced by a surplus of L-arginine and abrogated by N-monomethyl-L-arginine, a selective inhibitor of L-arginine-dependent effector mechanisms. In other macrophage/tumor cell combinations, such correlation was less obvious or not at all detectable, suggesting that, in these models, L-arginine-dependent reactive nitrogen intermediates are not or not alone responsible for the mediation of tumoricidal activity by activated macrophages. Collectively, the present findings suggest that the mechanism of tumor cell killing by activated macrophages may differ, depending on the tumor cell type and the pathway of macrophage activation. Among the various effector mechanisms considered to be involved in tumor cell killing by activated macrophages, L-arginine-dependent reactive nitrogen intermediates appear to hold a major role.

Animals↗
PubMed1990

Lymphokines and bacteria, that induce tumoricidal activity, trigger a different secretory response in macrophages.

The abilities of various macrophage-activating agents to trigger tumoricidal activity and/or the secretion of prostaglandin E2 (PGE2), interleukin 6 (IL 6) and transforming growth factor beta (TGF beta) in bone marrow-derived mononuclear phagocytes (BMM phi) in vitro were comparatively assessed. Induction of tumoricidal activity by lymphokines, that is only short-lived, was not associated with enhanced secretion of these activities by BMM phi; in contrast, incubation with heat-killed facultative intracellular bacteria resulted in persisting tumoricidal activity and in marked enhancement of the secretion of IL 6 and PGE2, but not of TGF beta activity. These findings support the concept that the pattern of the secretory response induced in macrophages by lymphokines differs from that triggered by bacteria and that the rapid decay of lymphokine-induced tumoricidal activity is not due to autocrine macrophage deactivation mediated by one of these agents alone.

Animals↗
PubMed1990

Binding of monomeric immunoglobulins by bone marrow-derived mononuclear phagocytes; its modulation by interferon-gamma.

The ability of resting and activated rat bone marrow-derived mononuclear phagocytes (BMM phi) to bind monomeric rat, mouse, and human IgG was determined by means of flow cytometry. Rat IgG2b bound with high affinity (Kd approximately equal to 3 x 10(-9) M); binding was optimal at 4 degrees C and was only little affected by trypsin treatment. The other IgG bound with only low affinity (rat IgG2a, mouse and human IgG) or not at all to rat BMM phi (rat IgG1, rat IgG2c). The binding of rat IgG2b was not affected by the presence of a surplus of low-affinity binding IgG, and vice versa, indicating that high- and low-affinity IgG bind to different sites. Binding of high- and low-affinity IgG as well as expression of MHC class II molecules and of tumoricidal activity by BMM phi was markedly enhanced by rat interferon-gamma in low concentration (0.1 to 1.0 IU IFN-gamma/ml). On the other hand, heat-killed Corynebacterium parvum organisms, that were equally potent in triggering tumoricidal activity, neither enhanced the binding of IgG nor the expression of MHC class II molecules by BMM phi, suggesting that these abilities are not necessarily closely related phenomena.

Animals↗
PubMed1990

Expression of cellular effector functions and production of reactive nitrogen intermediates: a comparative study including T lymphocytes, T-like cells, neutrophil granulocytes, and mononuclear phagocytes.

The ability of various cell types to secrete reactive nitrogen intermediates (RNI) upon functional activation was comparatively assessed. Neither in T lymphocyte clones mediating MHC class I or class II antigen-restricted killing via alpha/beta T cell receptor (TcR) or MHC-unrestricted killing via gamma/delta TcR, nor in peripheral blood mononuclear cells expressing natural killer or lymphokine-activated killer activity, target cell lysis was associated with detectable RNI production. Also, activated neutrophil granulocytes did not secrete RNI. In contrast, bone marrow-derived mononuclear phagocytes, activated to express tumoricidal activity, secreted marked RNI activity.

Animals↗
PubMed1990

Fermentation of bovine endothelial cells for preparation of endothelial cell-surface heparan sulphate.

The polysaccharide chains of a proteoheparan sulphate located on the endothelial cell surface are responsible for athrombogenicity of blood vessel walls. Mass cultivation of endothelial cells is the only way to isolate adequate amounts of this proteoheparan sulphate. In order to establish a method for fermentation of bovine endothelial cells, colonization of microcarriers, growth phase and cultivation of confluent carriers were optimized. The colonization process was varied relative to the number of beads, number of cells, total volume and kind of vessel. Two basal media were tested at different serum contents by growth assays. The same basal media without serum were supplemented with mitogen, bovine lipoprotein, insulin and transferrin and tested by activity assays on confluent cultures. The best method yields more than 80% of the cells on microcarriers. During the fermentation glucose and lactate concentrations were measured at constant perfusion rate and glucose consumption and lactate production were determined. Under optimized conditions we achieved a final cell titre of 4 x 10(9) cells/l and a calculated cell density of 7-9 x 10(4) cells/cm2 offered substrate surface. The minimal doubling time of the cell culture was about 18 h under optimized fermentation conditions. Removal of the core-protein by enzymatic digestion or beta-elimination releases the endothelial cell surface heparan sulphate.

Animals↗
PubMed1990

TNF alpha primes polymorphonuclear leukocytes for an enhanced respiratory burst to a similar extent as bacterial lipopolysaccharide.

We examined whether preincubating polymorphonuclear leukocytes (PMN) with TNF alpha would result in an enhanced respiratory burst upon subsequent stimulation by various agents. Bacterial lipopolysaccharide (LPS), a known primer of PMN, was used as control. We found that both LPS (0.01 to 10.0 microgram/ml) and recombinant TNF alpha (0.001 to 1.0 microgram/ml) act as direct stimulants of PMN as measured by chemiluminescence. Sixty minutes of preincubation of PMN with 1 microgram/ml TNF alpha or 10 micrograms/ml LPS resulted in similar priming for the respiratory burst elicited by opsonized zymosan, phorbol myristate acetate, zymosan, zymosan-activated serum, aggregated immunoglobulin, and f-met-leu-phe (FMLP) depending on the method of measurement used, i.e., chemiluminescence, production of O2-, and H2O2. Priming with TNF alpha for an enhanced response to stimulation by FMLP could be abrogated by anti-TNF alpha antibody. Cell-surface receptor numbers and binding-affinity constants for FMLP remained stable under conditions leading to priming. We conclude that TNF alpha is able to prime PMN for an enhanced respiratory burst to a similar extent as with LPS. Because PMN cell-surface receptors for FMLP are unaltered by priming, the enhanced respiratory burst seems to be due to changes in intracellular metabolism.

Antibodies↗
PubMed1990

The mechanics of notochord elongation, straightening and stiffening in the embryo of Xenopus laevis.

We have examined the biomechanical development of the notochord of Xenopus early tail-bud embryos by: (1) quantifying morphological and mechanical changes in the embryo during stages 20-28, and (2) conducting manipulative experiments to elucidate mechanical roles of various components of the notochord. The notochord, which is composed of a stack of flat cells surrounded by a connective tissue sheath, elongates dramatically and begins straightening between stages 21 and 25. At this time the fiber density in the notochord sheath goes up, the osmotic activity of the notochord cells increases, vacuoles within these cells swell, the internal pressure of the notochord increases 2- to 3-fold, and the flexural stiffness of the notochord rises by an order of magnitude. We suggest that the tendency of the notochord cells to osmotically swell is resisted by the sheath, thereby permitting the internal pressure to rise. This pressure increase results in the greater stiffness that permits the notochord to elongate and straighten without being buckled by the surrounding tissues.

Animals↗
PubMed1990

Academic predictors of success on the NCLEX-RN examination for associate degree nursing students.

The purpose of this study is to examine the relationship between selected admission variables (entrance GPA, ACT subtests scores in English and mathematics, composite ACT scores), age, perception of role strain, achievement in clinical and nursing courses, achievement on NLN examinations, exit GPA, and performance on NCLEX-RN examination. Data were attained from records of 146 associate degree graduates who were admitted to a specially-designed associate degree program in nursing and on those graduates who wrote the NCLEX-RN examination in July 1987 and July 1988. Pearson product moment correlations and stepwise multiple regression analyses were used to identify the relationship between the predictor variables (admission criteria, age, perception of role strain, achievement in clinical and nursing courses), achievement on NLN examinations, exit GPA, and the criterion variable (scores on the NCLEX-RN examination). The best predictor for performance on the NCLEX-RN of the selected admission variables, age, perception of role strain, and exit GPA, were exit GPA (R = .71) and ACT composite scores (R = .75). The ACT math, ACT English scores, entrance GPA, age, and perception of role strain, had no predictive value. The best predictor for performance on the NCLEX-RN of nursing theory course and clinical course grades were the two theory courses in the second year of the program NUR 2712 (R = .77) and NUR 2713 (R = .79). NUR 2711 and 2711L, NUR 2712L, 2713L, and 2813 had no predictive value for success on the NCLEX-RN.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1990

[Gastroesophageal reflux and lung diseases].

In a number of patients there is evidence of an unfavourable interaction between gastro-oesophageal reflux (GER) and pulmonary disease, that takes the form of a vicious circle: first GER can induce and maintain chronic bronchopulmonary inflammation by recurrent unnoticed aspirations and, secondly chemical irritation of the oesophageal mucosa causes airway obstruction by vagally-mediated reflexes. Obstructive airway disease in turn favours GER via anatomical functional and physiological factors. Thus the prevalence of GER is increased to 30-40% in patients with asthma and chronic bronchitis, as compared with only 5-10% in the general population. A positive history of productive cough, nocturnal respiratory symptoms and recurrent hoarseness may be helpful in detecting an important relationship between GER and chronic airway disease. The modified Bernstein-test, radionuclide studies and detailed sleep studies are suitable methods of establishing the diagnosis. Antireflux diets, H2-antagonists and antacids are accepted treatment in the adult, and may obviate surgical procedures in most patients. In clinical practice the relationship between GER and pulmonary diseases should be considered routinely, in order to initiate early and effective treatment and to end the vicious circle.

Airway Resistance↗
PubMed1989

[Transtracheal oxygen therapy in obstructive sleep apnea syndrome].

In a prospective trial we studied the effect of nocturnal low-flow oxygen administration in 10 consecutive patients with obstructive sleep apnea. In 5 patients the clinical symptoms disappeared completely under nasal oxygen administration and hypoxic episodes decreased from an average of 28 to 3 per hour. In the remaining 5 patients nasal oxygen alone was not sufficiently effective. After insertion of a transtracheal catheter for nocturnal oxygen delivery, however, in 4 of these 5 patients (one patient refused the procedure) clinical symptoms improved and hypoxic episodes were reduced to 3 per hour (48/h without oxygen, 34/h with nasal oxygen). The favourable effect of transtracheal oxygen therapy may be due to the improved oxygenation provided by this technique, as well as to a "pneumatic splint" as a result of increased positive pressure in the central airways during prolonged apneic episodes. Thus, transtracheal oxygen therapy can be considered an efficient alternative to nasal CPAP in patients with severe obstructive sleep apnea syndrome.

Adult↗
PubMed1989

Abilities of activated macrophages to manifest tumoricidal activity and to generate reactive nitrogen intermediates: a comparative study in vitro and ex vivo.

The abilities of lymphokines and heat-killed bacteria to induce and to maintain tumoricidal activity and/or the secretion of reactive nitrogen intermediates (RNI) were comparatively assessed in bone marrow-derived mononuclear phagocytes (BMM phi) in vitro and in adherent peritoneal cells (APC) ex vivo. In showing that the kinetics of tumoricidal activity and of secretion of RNI induced by macrophage-activating agents in BMM phi and/or in peritoneal cells do largely parallel each other, the present findings provide evidence for a role of RNI in tumor cell killing by activated macrophages both in vitro and in vivo.

Animals↗