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Biomedical subjects

C E McCall

Publications and source records attributed to C E McCall.

At least 55 records · Page 3Linked to original sources
PubMed1985

Histopathologic features of phorbol myristate acetate-induced lung injury.

Rabbits given daily intravenous injections of phorbol myristate acetate (PMA) develop acute and chronic pulmonary disease. We distinguished three phases in the histologic progression of the lung injury. An acute phase (occurring within 1.5 hours of the first injection) involved hemorrhagic pneumonitis, increased lung weight, and increased numbers of neutrophils as well as erythrocytes in alveolar fluid. The intermediate phase (occurring 1 to 7 days after the initial injection) involved interstitial pneumonitis: neutrophils and macrophages infiltrated into lung interstitium and alveolar fluid. The relative number of type II alveolar epithelial cells increased dramatically and lung weight became maximal during this phase. In the chronic phase (occurring within 14 days and lasting greater than 77 days) diffuse interstitial fibrosis progressed, whereas inflammatory changes abated. Animals treated daily with PMA developed a linear increase in lung hydroxyproline content beginning on the 7th day of treatment. Values increased to three to four times above controls by day 77. Animals treated with PMA for only 14 days and sacrificed up to 63 days thereafter had lung hydroxyproline values that were intermediate between controls and animals injected daily for 77 days. Their fibrosis neither progressed nor reversed when PMA treatment was stopped. In contrast, animals receiving a single dose of PMA developed only the acute and intermediate phases of injury; no detectable fibrosis occurred, and their lung reactions resolved completely. Finally, animals made neutropenic with nitrogen mustard did not respond to PMA with increased lung weight or changes in alveolar lavage fluid cellularity during the early or intermediate phases of the disease. They did, however, exhibit increased interstitial cellularity. Thus, PMA produces abrupt pneumonitis that progresses to fibrosis. The acute and intermediate phases of injury are neutrophil dependent and reversible, whereas the chronic fibrotic phase is irreversible and requires continued PMA injections for progression.

Acute Disease↗
PubMed1984

Diacylglycerols enhance human neutrophil degranulation responses: relevancy to a multiple mediator hypothesis of cell function.

At 10 microM, 1-0-oleoyl-, 1-0-palmitoyl-, and 1-0-myristoyl-2-0-acetyl-glycerol weakly stimulated neutrophils to release lysozyme, an enzyme in secondary granules, but had no such effect on the release of a primary granule enzyme, beta-glucuronidase. The glycerides (1-10 microM) had a second effect on both granule populations: they enhanced the degranulating potencies of leukotriene B4, platelet-activating factor, a formylated oligopeptide, and C5a by 10- to 30-fold. In contrast, they were much less effective in enhancing responses to ionophore A23187 and partially inhibited responses to phorbol myristate acetate. The diether analogue, 1-0-hexadecyl-2-0-ethylglycerol was inactive in these regards. We suggest that diacylglycerols are a novel class of bioactive products mobilized from phosphoglycerides in stimulated neutrophils; as co-products of this mobilization, platelet-activating factor and leukotriene B4 may interact with diacylglycerols to promote cell function.

Animals↗
PubMed1984

Neutrophil degranulation responses to combinations of arachidonate metabolites and platelet-activating factor.

Polymorphonuclear neutrophils, when stimulated, rapidly form platelet-activating factor (PAF) and metabolize their arachidonate into 5-hydroperoxyeicosatetraenoate (5-HPETE), 5-hydroxyeicosatetraenoate (5-HETE), leukotriene (LT)A4, and LTB4. PAF and LTB4 degranulate neutrophils; 5-HETE, while lacking intrinsic degranulating actions, potentiates these responses. We now find that: a) 5-HPETE similarly potentiates the two lipids and has weak degranulating actions, b) LTA4 and LTB4 degranulate neutrophils by a common pathway, c) PAF degranulates neutrophils by a distinctly different pathway, d) the actions of either LT are additive to those of PAF, e) 5-HETE is particularly effective in potentiating response to combinations of PAF and LTB4, and f) combinations of the lipids partially circumvent requirements for cytochalasin B in these degranulation responses. Thus, the five lipids can be classified into potentiators (i.e., 5-HPETE and 5-HETE) and two types of independently acting agonists (i.e., LT's are one type, PAF a second type). At low concentrations, potentiator, LT, and PAF can all interact to produce prominent responses. They may similarly interact to promote function within their cells of origin.

Arachidonic Acids↗
PubMed1983

5-L-hydroxy-6,8,11,14-eicosatetraenoate potentiates the human neutrophil degranulating action of platelet-activating factor.

Platelet-activating factor (AAGPC) and two of its structural analogues degranulated human neutrophils with respective potencies that were increased up to 100 to 1000-fold by 16 nM to 5 microM of 5-L-hydroxyeicosatetraenoate (5-L-HETE). 5-rac-HETE had similar actions but 8-rac-HETE was without effect. Furthermore, 5-L-HETE did not influence the degranulating actions of C5a, A23187 or a formalated oligopeptide chemotactic factor and none of the HETEs, by themselves, caused degranulation. Thus, 5-L-HETE and AAGPC selectively interact to induce degranulation. Since these products rapidly form in stimulated PMNs, they may serve as potentiator and agonist, respectively, to transduce biological signals into cell function.

Arachidonic Acids↗
PubMed1983

Platelet-activating factor effects on pulmonary ultrastructure in rabbits.

Morphometric analysis of endothelium in rabbit lungs demonstrated a dramatic effect of platelet-activating factor (PAF) on the ultrastructure of pulmonary vasculature. Plasmalemmal vesicles in capillaries were increased both in size (638 A PAF vs 538 A control) and in number (386/micrograms 3 cytoplasm PAF vs 125/micrograms 3 cytoplasm control) when PAF was administered as a single acute low dose (chi less than 3 micrograms/kg). High concentrations of PAF (chi greater than 3 micrograms/kg) as a single acute dose also increased vesicle number (203/micrograms 3 cytoplasm), but frequently precipitated the respiratory distress syndrome. Chronic administration of PAF with daily doses over periods of either 3.5 or 7 weeks resulted in changes paralleling the acute observations, but did not lead to more extensive lung disease.

Animals↗
PubMed1983

Clinical evaluation of moxalactam: evidence of decreased efficacy in gram-positive aerobic infections.

Moxalactam was used as initial, empirical therapy in 69 patients with a variety of serious bacterial infections, 32% of which were accompanied by bacteremia. Overall, the success rate was 83% and drug-related adverse effects were minimal. The drug was less efficacious in infections caused by aerobic gram-positive pathogens than it was in those caused by gram-negative pathogens. The following gram-positive organisms were associated with special problems during moxalactam therapy: Streptococcus pneumoniae (development of meningitis and a relapse of pneumonia with a more resistant strain), Staphylococcus epidermidis (in vivo emergence of moxalactam resistance, and the enterococci (failure of therapy and a fatal superinfection. Moxalactam performed well in infections caused by most gram-negative organisms, including aminoglycoside-resistant strains, but the previously reported emergence of gram-negative bacillary resistance to moxalactam during therapy was reconfirmed in our series with Serratia marcescens. The use of moxalactam in the treatment of gram-negative meningitis was further supported by a patient with meningitis-ventriculitis caused by Bacteroides fragilis who was cured with moxalactam after failure on chloramphenicol.

Adolescent↗
PubMed1983

Potentiating actions of hydroxyeicosatetraenoates on human neutrophil degranulation responses to leukotriene B4 and phorbol myristate acetate.

Previous studies demonstrated that the arachidonate metabolite, 5-L-hydroxy-6,8,11,14-eicosatetraenoate (5-L-HETE), potentiates the human polymorphonuclear neutrophil degranulation response to platelet-activating factor without influencing this response when elicited by C5a, a formylated oligopeptide, or ionophore A23187. We now find that the HETE amplifies the degranulation response to phorbol myristate acetate and leukotriene B4. The HETE was active in dosages as low as 50 nM; at 5 microM, it produced 1000-, 30-, and 5-fold enhancements in the potencies of platelet-activating factor, phorbol myristate acetate, and leukotriene B4, respectively. 5-rac-HETE had similar actions but 8-rac-HETE, 9-rac-HETE, and 12-L-HETE possessed little or no effects. Thus, 5-L-HETE potentiates the actions of various structurally unrelated degranulating agents; it particularly influences those compounds which, like 5-L-HETE itself, are formed by stimulus-activated neutrophils, viz., leukotriene B4 and platelet-activating factor. These latter two lipids and 5-L-HETE may interact to mediate neutrophil degranulation responses.

Arachidonic Acids↗
PubMed1983

Platelet-activating factor and analogues: comparative studies with human neutrophils and rabbit platelets.

Platelet-activating factor and 12 structural analogues stimulated rabbit platelets to aggregate and release [14C]-serotonin. They likewise caused human neutrophils to aggregate, degranulate, and take up [3H]-deoxyglucose. Their respective potencies, which varied by 4-5 orders of magnitude, correlated highly (r greater than or equal to 0.93) in all assays. These compounds also selectively desensitized neutrophils to the degranulating actions of platelet-activating factor but not to C5a or a formylated oligopeptide. Three other analogues with structures quite similar to platelet-activating factor were unable to activate or desensitize the cells. Hence, the structure-activity relations of the analogues in several assays of platelet and neutrophil function were similar and they stimulated neutrophils by a common activation mechanism that differed from those used by C5a or formylated oligopeptides. These data are consistent with the notion that platelet-activating factor activates and desensitizes various target cells through stereospecific receptors. Apparently, these putative receptors on neutrophils and platelets have similar structural specificities for platelet-activating factor and its analogues.

Animals↗
PubMed1982

The effect of free radical derived hydroxyeicosatetraenoic acids on hexose transport in the human polymorphonuclear leukocyte.

The following racemic hydroxyicosatetraenoic acids were prepared and assayed for their ability to stimulate hexose transport in human polymorphonuclear leukocytes: 15-, 12-, 11-, 9-, 8-, and 5-hydroxyicosatetraenoic acids. The compounds were isolated from reduced, autoxidized arachidonic acid. The results demonstrate that only the 12- and 5-hydroxyicosatetraenoic acids are biologically active inducing half-maximal responses at 820 and 176 nM, respectively. Thus, the bioactions of hydroxicosatetraenoates ae crucially dependent upon the position of the hydroxy residue. Response to both hydroxyicosatetraenoates was effectively blocked by two inhibitors of arachidonic acid metabolism: nordihydroguaiaretic acid and indomethacin. A third arachidonic acid antimetabolite, 5, 8, 11, 14-eicosatetraynoic acid, completely inhibited the response to 12-HETE but caused only partial inhibition of the response to 5-HETE.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1982

Neutropenia induced by systemic infusion of 5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid: correlation with its in vitro effects upon neutrophils.

5(S), 12(S)-Dihydroxy-cis-14,trans-6,8,10-eicosatetraenoate (compound I), 5(S),12(R)-dihydroxy-cis-14,trans-6,8,10-eicosatetraenoate (compound II), and 5(S),12(R)-dihydroxy-cis-6,14,trans-8,10-eicosatetraenoate (compound III) were prepared from rabbit peritoneal neutrophils challenged with arachidonic acid plus ionophore A23187. Each arachidonate metabolite caused rabbit neutrophils to aggregate and, in cells treated with cytochalasin B, release granule-bound enzymes. Compound III was 10- to 100-fold more potent than compounds II and I. When intravenously infused into rabbits at doses of 100--1,000 ng/kg, compound III induced abrupt, profound, transient neutropenia associated with a rapidly reversing accumulation of neutrophils in the pulmonary circulation. This in vivo action correlated closely with the ability of the fatty acid to activate neutrophils in vitro: neutropenia, aggregation, and degranulation occurred at similar doses of stimulus and the rapid, reversing kinetics of the neutropenic response paralleled the equally rapid, reversing formation of aggregates. The fatty acid did not alter the circulating levels of lymphocytes or platelets and did not aggregate platelets in vitro. At comparable doses (i.e., 100--1,000 ng/kg), compounds I and II did not cause neutropenia. Thus, compound III possesses a high degree of structural and target-cell specificity in stimulating neutrophils in vitro and in vivo. Clinical and experimental syndromes associating neutropenia with increased levels of circulating arachidonate metabolites may involve compound III as a mediator of neutrophil sequestration in lung.

Agranulocytosis↗
PubMed1982

Rocky Mountain spotted fever. Serological evidence of previous subclinical infection in children.

Serological tests for Rocky Mountain spotted fever were performed on single serum specimens from sixth graders from Forsyth County, North Carolina, an area highly endemic for this disease. Five of 508 *.098%) sera were positive (titer greater than or equal to 1:64) using the indirect fluorescent antibody method. Elevated Proteus agglutination antibody titers (greater than 1:160) to OX-19, but not ot OX-2, were common (19.6%) in these children. No correlation of those with positive OX-19 titers could be made with the cases demonstrating elevated indirect fluorescent antibody titers or with a history of urinary tract infection. These data suggest that the increased prevalence of elevated Proteus OX-19 antibody levels makes a single high titer unreliable in the diagnosis of Rocky Mountain spotted fever and that naturally acquired mild or asymptomatic subclinical cases of Rickettsia rickttsii infection occur.

Antibodies, Bacterial↗