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Biomedical subjects

R L Baehner

Publications and source records attributed to R L Baehner.

At least 73 records · Page 4Linked to original sources
PubMed1982

Monocyte aggregation and superoxide anion release in response to formyl-methionyl-leucyl-phenylalanine (FMLP) and platelet-activating factor (PAF).

Like the PMN, human peripheral blood monocytes were capable of aggregating in response to FMLP and PAF. Monocyte aggregation was dependent on glycolysis and the presence of divalent cations. Unlike the PMN, monocyte aggregation in response to FMLP was not accompanied by degranulation, nor was it potentiated by cytochalasin B. Furthermore, cytochalasin B and its cogenitor, dihydrocytochalasin B, inhibited aggregation in response to PAF. PAF and FMLP appeared to react with the monocyte at separate receptors because sequential challenge of the monocyte with the same agents failed to elicit further aggregation, whereas rechallenge with the alternative agent induced further aggregation. Because the monocyte will aggregate to chemotactic agents in vitro, it is likely that the cell will be affected by these agents in vivo, which could lead to leukoembolization of circulating monocytes.

Calcium↗
PubMed1982

Relation of respiratory burst and arachidonate metabolism during phagocytosis by guinea pig alveolar macrophages.

We have examined the respiratory burst and arachidonic acid oxygenation that accompany phagocytosis in macrophages. Guinea pig alveolar macrophages were stimulated with opsonized zymosan in the presence of inhibitors of arachidonic acid metabolism: ASA, indomethacin, and ETYA, ASA, at concentrations as high as 60 micrograms/ml, had no effect on either oxygen consumption or superoxide ion formation. Indomethacin (4 x 10(-4) M) and ETYA (2 x 10(-5) M) did inhibit oxygen utilization and superoxide production. However, no indomethacin or ETYA inhibition of oxygen utilization was detected in the presence of 1 mM KCN, suggesting that the inhibitable portion of the respiratory burst observed with indomethacin or ETYA was dependent on mitochondrial respiration. Further study with ETYA showed that the inhibitor at 2 x 10(-5) M had little effect on uptake of 125I-labeled zymosan but did abolish the conversion of 14C-arachidonic acid to a compound that co-migrated with authentic 12-HETE on silica gel plates. Lower concentrations of ETYA (5 x 10(-6) M), which had no effect on the respiratory burst of phagocytosing alveolar macrophages, also inhibited arachidonic acid metabolism. We conclude therefore that the inhibition of oxygen consumption and superoxide production by ETYA at 2 x 10(-5) M is unrelated to inhibition of arachidonic acid metabolism. Furthermore, the oxygenation of arachidonic acid requires little of the oxygen consumed by phagocytosing alveolar macrophages.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1982

Metabolic, membrane, and functional responses of human polymorphonuclear leukocytes to platelet-activating factor.

The phospholipid mediator of anaphylaxis, platelet-activating factor (PAF) is chemotactic for polymorphonuclear leukocytes (PMN). We have examined this agent's effects on several other PMN functions. Human PMN were prepared from heparinized venous blood by Ficoll gradient. Metabolic burst was examined by measurement of O2 use and O2.- production in the presence or absence of PAF (10(-6)--10(-9) M). Unless cells were treated with cytochalasin-B (5 micrograms/ml), no significant respiratory burst was demonstrated. However, pretreatment with PAF (10(-7) M) enhanced approximately threefold the O2 utilization found when cells were subsequently stimulated with 10(-7) M FMLP. PAF also stimulated arachidonic acid metabolism in 14C-arachidonic acid-labeled PMN. Thin-layer chromatography analysis of chloroform-methanol extracts showed substances that comigrated with authentic 5-hydroxyeicosatetraenoic acid had a marked increase in radioactivity following PAF stimulation at 10(-7) M. PAF failed to stimulate release of granule enzymes, B-glucuronidase, lysozyme, or myeloperoxidase unless cytochalasin-B were added. PAF from 10(-6) M to 10(-10) M affected PMN surface responses. PMN labeled with the fluorescent dye, chlorotetracycline, showed decreased fluorescence upon addition of PAF, suggesting translocation of membrane-bound cations. Further, the rate of migration of PMN in an electric field was decreased following PAF exposure, a change consistent with reduced cell surface charge. PMN self-aggregation and adherence to endothelial cells were both influenced by PAF (10(-6) M--10(-9) M). Aggregation was markedly stimulated by the compound, and the percent PMN adhering to endothelial cell monolayers increased almost twofold in the presence of 10(-8) M PAF. Thus, PAF promotes a variety of PMN responses: enhances respiratory burst, stimulates arachidonic acid turnover, alters cell membrane cation content and surface charge, and promotes PMN self-aggregation as well as adherence to endothelial cells.

Cell Adhesion↗
PubMed1982

Correlation of in vitro and in vivo effects of gold compounds on leukocyte function: possible mechanisms of action.

The anti-inflammatory effects of gold compounds include suppression of PMN lysosomal enzyme release. Since lysosomal products can provoke PMN aggregation, we assessed the effect of two gold compounds, auranofin and GST, on suppressing aggregation, degranulation, and metabolic functions of the cells. Aggregation of 1 x 10(7) cytochalasin B-treated PMNs in response to 2 x 10(-7)M FMLP, as assessed by light scattering, was inhibited in a dose-dependent fashion by both drugs. Concentrations of auranofin ranging from 5 to 20 microM caused 30.8% to 89% inhibition, whereas 200 microM GST reduced aggregation by only 32%. FCS or BSA added to suspensions of normal PMNs considerably reduced the gold compound inhibitory effect on PMN aggregation. Cell viability assessed by dye exclusion and lactate dehydrogenase release was unaffected by the drugs. The suppressive activities of the drugs could not be removed by washing the PMNs. Correspondingly, the drugs suppressed lysosomal enzyme release induced by FMLP of PMNs rendered secretory with cytochalasin B. Concentrations of 20 microM auranofin and 200 microM GST resulted, respectively, in a 61.5% and 19.3% reduction of release of lysozyme, 61.7% and 27.1% reduction of beta-glucuronidase, 84.8% and 33.7%s reduction of myeloperoxidase, and 50.0% and 25.0% reduction of lactoferrin. Furthermore, auranofin inhibited 14C-1-glucose oxidation through the hexose monophosphate shunt in response to stimulation by either PMA or methylene blue. The in vivo studies suggested that auranofin could prevent neither neutropenia induced by zymosan-activated serum nor a corresponding rise in plasma lactoferrin levels. These findings suggest that the beneficial effect of gold compounds in rheumatoid arthritis are unlikely to be related to their ability to dampen PMN activation in vivo.

Animals↗
PubMed1982

Isolated testicular leukemia following bone marrow transplant for acute lymphocytic leukemia. The need for pretransplant testicular biopsies.

Bone marrow transplantation has become an accepted mode of treatment for children with acute myelocytic leukemia in their first remission and acute lymphocytic leukemia after their first bone marrow relapse. Two-year survival rates of 50% can be achieved in patients undergoing transplant during remission, in contrast to a 2-year survival of 15% in those undergoing transplant while still in marrow relapse. Recurrence of bone marrow leukemia relapse is a significant cause of marrow transplant failure. Overt or occult testicular relapse occurs in 10-15% of males with acute lymphocytic leukemia receiving or having completed standard therapy regimens for control of their disease and frequently leads to a subsequent bone marrow relapse. This paper describes a child with acute lymphocytic leukemia who received a successful marrow transplant following bone marrow relapse and developed testicular leukemia relapse approximately 20 months after transplant. The experience with this child suggests that bilateral testicular biopsies should be a mandatory part of the routine evaluation to screen for residual leukemia before bone marrow transplantation.

Biopsy↗
PubMed1982

Mechanism of dexamethasone inhibition of chemotactic factor induced granulocyte aggregation.

The reaction of FMLP with granulocytes causes aggregation and degranulation and enhances adherence to endothelium. To evaluate whether prevention of granule extrusion could impair these granulocyte activities, granulocytes were treated with either dexamethasone or hydrocortisone prior to treatment with FMLP. Dexamethasone was added to suspensions of cytochalasin B-treated granulocytes; it markedly impaired the aggregation response of the granulocytes of FMLP. When cytochalasin-B was not used, granulocyte aggregation in response to FMLP or PMA was inhibited by dexamethasone. Although dexamethasone prevented aggregation of cells following stimulation with FMLP or PMA, it failed to prevent the aggregation of granulocytes induced by rabbit lactoferrin. Adherence of granulocytes to human endothelial monolayers was enhanced by FMLP; dexamethasone inhibited the enhancement. However, with the addition of human lactoferrin to the granulocytes exposed to dexamethasone, the cells were able to adhere as well to endothelium as the cells exposed to FMLP but free of dexamethasone. When cytochalasin-B-treated granulocytes were incubated with dexamethasone or hydrocortisone prior to the addition of FMLP, the subsequent release of lactoferrin was substantially blocked, whereas the release of the primary granule products, lysozyme and beta-glucuronidase, was attenuated but not completely blocked. Thus, corticosteroids might block chemotactic-factor-induced granulocyte aggregation by selectively preventing release of specific granule products that contribute to and sustain aggregation.

Cell Aggregation↗
PubMed1982

Neutropenia induced by systemic infusion of lactoferrin.

Rabbit granulocyte lactoferrin, when infused into hamsters or rabbits, induces transient neutropenia, and in hamsters the lactoferrin promotes adherence of the granulocytes to the endothelial cell wall as monitored visually. In contrast, neither rabbit granule lysozyme nor human transferrin induces neutropenia in the rabbit nor does transferrin or bovine serum albumin affect the adherent properties in vivo of the phagocytic cells of the hamster. Thus lactoferrin enhances granulocyte adherence both in vivo and in vitro. It would appear that the promotion of margination of leukocytes by lactoferrin in vivo may contribute to the phenomenon of neutropenia during activation of granulocytes by chemotactic factors.

Agranulocytosis↗
PubMed1982

Enrichment by counterpart centrifugal elutriation of human lymphocytes cytotoxic to human tumour cells.

The enriched fractions of cytotoxic cells responsible for natural killer (NK) activity against both human sarcoma and neuroblastoma (LA-N2) cell lines were readily obtained by countercurrent centrifugal elutriation (CCE). The NK cells were obtained in the larger lymphocyte fractions (fraction 6 +/- 1), having a mean cell volume of 180 u3. The cytotoxic-enriched fraction contained 51% large lymphocytes having cytoplasmic granules. On the other hand, monocytes were purified to greater than 90% and isolated in another fraction (final fraction) and these cells had the lowest NK activity against both human tumour cell lines. However, compared with the lymphocyte fractions, small and large monocytes displayed greater antibody-dependent cellular cytotoxicity (ADCC) activity against human B erythrocytes. These results indicate that NK found to have activity against both tumour cells lines were larger lymphocytes, not small monocytes. Thus, countercurrent centrifugal elutriation (CCE) can provide a sensitive method to obtain enriched fractions of large lymphocytes contained tumoricidal activity against human sarcoma and neuroblastoma cell lines.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1981

The myeloproliferative reaction in a child with Down syndrome: cytological and chromosomal evidence for a transient leukemia.

Infants with Down syndrome occasionally develop marked myeloproliferative reactions (MPR) indistinguishable from acute myelocytic leukemia but which spontaneously regress. Most authors have attributed MPR to immature or defective control on bone marrow development. In this report serial cytomorphologic and chromosomal findings in the bone marrow and peripheral blood of a child with the MPR suggests that MPR may be due to a spontaneously regressing clone of malignant cells. At the height of the myeloproliferative response, chromosomal studies demonstrated a clone of blast-like cells with a 21-22 translocation consistent with Down Syndrome and an X-8 translocation which was present only in the initial peripheral blood analysis harvested at 24 hours but was not present in the 72 hours samples. This X-8 translocation was not demonstrated in bone marrow or peripheral blood samples obtained at random times throughout the one year followup. During this period there was complete resolution of the MPR. In addition the chromosomes from one cell demonstrated several double minutes at the time of the MPR. Double minutes have previously been reported only in malignant diseases, especially tumors of neural origin and leukemia. These findings raise questions about the benign origin of the MPR and support the idea the MPR may be the result of a spontaneously regressing clone of malignant cells.

Bone Marrow↗
PubMed1981

Characteristics of children with acute nonlymphocytic leukemia in long-term continuous remission: a report for Childrens Cancer Study Group.

Children and young adults less than 18 years of age with acute nonlymphocytic leukemia who remained in long term bone marrow and extramedullary remission for two years or longer since starting maintenance were compared to the remaining responders for the following characteristics: cell type, sex, age at diagnosis, race, pretreatment, white blood count, length of time from start to induction therapy to achievement of an M1 marrow, marrow rating at day 56 of therapy, marrow rating at the start of maintenance therapy, and specific study. Forty-eight patients of a group of 333 qualified as having long term remission (14.4%). Multivariant analysis indicated that patients between the ages of 3 and 10 years (p = 0.003) as well as the length of time to achieve an M1 marrow from the start of treatment (p = 0.03) were the only characteristics associated with achievement of a long term remission. Maintenance therapy was discontinued in 15 patients from 2.5 to 4.8 years after start of maintenance and all patients remained in bone marrow remission of periods from 0+ to 3.0+ years after stopping treatment. Of the 33 who have remained on a continuous maintenance therapy 12 have had bone marrow relapses. These data confirm the prognostic value of age and length of time to achieve remission during induction in acute nonlymphocytic leukemia and suggest that there may be no significant benefit from maintenance therapy continued beyond 2 years for patients in their initial remission.

Acute Disease↗
PubMed1981

Fluidity properties and liquid composition of erythrocyte membranes in Chediak-Higashi syndrome.

We have earlier shown through electron spin resonance (ESR) studies of leukocytes that membranes of cells from both Chediak-Higashi syndrome (CHS) mice and humans have abnormally high fluidity. We have extended our studied to erythrocytes. Erythrocytes were labeled with the nitroxide-substituted analogue of stearic acid, 2-(3-carboxypropyl)-4,4-dimethyl-2-tridecyl-3-oxazolidinyloxyl, and ESR spectra were obtained. Order parameter, S, at 23 degrees C, was 0.661 and 0.653 for erythrocytes of normal and CHS mice (P less than 0.001). S was 0.684 for normal human erythrocytes and 0.675 (P less than 0.001) for CHS erythrocytes at 25 degrees C. Because S varies inversely to fluidity, these results indicate that CHS erythrocytes tend to have higher fluidity than normal. In vitro treatment of both mice and human CHS erythrocytes with 10 mM ascorbate returned their membrane fluidity to normal. We prepared erythrocyte ghosts and extracted them with CHCl3:CH3OH (2:1). Gas-liquid chromatography analysis showed a greater number of unsaturated fatty acids for CHS. The average number of double bonds detected in fatty acids for mice on a standard diet was 1.77 for normal and 2.02 for CHS (P less than 0.04); comparison of human erythrocytes from one normal control and one CHS patient showed a similar trend. Our results suggest that an increased proportion of unsaturated fatty acids may contribute to increased fluidity of CHS erythrocytes. Our observation that both leukocytes and erythrocytes of CHS have abnormal fluidity indicates that CHS pathophysiology may relate to a general membrane disorder.

Animals↗
PubMed1981

Changes in energy metabolism, structure and function in alveolar macrophages under anaerobic conditions.

To determine whether the change in energy metabolism of guinea-pig alveolar macrophages (AM) would alter their function to resemble peritoneal macrophages (PM), AM were exposed to strict anaerobic environments for 96 h. Exposure of cultivated AM to hypoxic conditions resulted in a decreased activity of cytochrome oxidase, a key enzyme in oxidative phosphorylation, whereas pyruvate kinase activity, a key enzyme in glycolysis, increased to levels observed in PM. Under hypoxic conditions the total mitochondrial structure available for respiratory activity also decreased in the glycolytic energy-dependent AM. Accompanying the shift in energy metabolism, adaptive changes in the functional responses of lectin-receptor activity occurred in the AM exposed to hypoxic conditions. Culture of AM in an anaerobic environment led to a loss in their ability to mobilize their lectin receptors in response to cytochalasin B, whereas AM maintained in an aerobic environment could mobilize their receptors in response to either cytochalasin B and D. Alterations in O2 tension affect AM metabolism, morphology and function and indicate that the AM is able to change its energy metabolism according to environmental circumstances.

Anaerobiosis↗
PubMed1981

Rabbit cationic protein enhances leukocyte adhesiveness.

Cationic protein purified from rabbit peritoneal polymorphonuclear leukocytes (PMN) was demonstrated to incite autoaggregation of the rabbit PMN and promote adhesiveness of human PMN to endothelial cells. PMN aggregation induced by supernatants derived from secretory PMN was blocked by a specific anticationic protein antibody. These studies reveal that a positively charged protein derived from the PMN can alter surface properties of the PMN itself and imply a role for this protein in PMN immobilization at inflammatory sites.

Animals↗