Complex ceruminous gland adenocarcinoma in a brown-footed ferret (Mustela putorius furo).
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Adenocarcinoma↗
Biomedical subjects
M R White
Publications and source records attributed to M R White.
Evaluation of an orally administered vaccine, using hydrogels containing bacterial exotoxins of Pasteurella haemolytica, in cattle.
Poly(methacrylic acid) hydrogels were tested for oral delivery of a vaccine against Pasteurella haemolytica infection in cattle. Culture supernatants of P haemolytica, the most common bacterium associated with pneumonia in cattle, were used as the antigens in the vaccine. Hydrogels containing culture supernatants were administered orally to calves. Calves were then challenge-exposed with virulent P haemolytica. Calves were euthanatized 3 days after challenge exposure. The lungs of each calf were scored for severity and size of pneumonic lesions. Results indicated that vaccinated calves had smaller, less severe pneumonic lesions and lived longer than nonvaccinated calves. These results indicated that hydrogels can be used to deliver vaccines orally to calves to enhance resistance to pneumonia caused by P haemolytica.
Administration, Oral↗
Conglutinin acts as an opsonin for influenza A viruses.
Since the 1940's, non-Ig inhibitors of influenza A virus (IAV) hemagglutination activity and infectivity have been recognized in mammalian sera. Recently, the heat labile (beta) inhibitor of this type was identified by indirect methods as the lectin, conglutinin. In support of this hypothesis, we found that purified conglutinin strongly inhibited hemagglutination activity and infectivity of IAV. By using IAV strains with specific variations in glycosylation of the hemagglutinin molecule, we showed these effects to be mediated by binding of conglutinin to high mannose carbohydrate attachments on the viral hemagglutinin. Through the same mechanism conglutinin caused aggregation of IAV particles. Human neutrophils produce hydrogen peroxide upon exposure to IAV. Also, after a brief period of exposure to IAV, neutrophils exhibit depressed responsiveness (deactivation) upon exposure to other stimuli (e.g., chemotactic peptides). These phenomena may be related to the in vivo inflammatory response during IAV infection, and to the propensity of IAV-infected subjects to suffer bacterial superinfection. Pre-incubation of IAV with conglutinin markedly potentiated human neutrophil hydrogen peroxide production in response to the virus. This effect correlated with the ability of conglutinin to aggregate the virus. IAV treated with conglutinin also caused significantly less neutrophil deactivation than did the unopsonized virus. These enhancements of neutrophil respiratory burst responses by conglutinin were again mediated by binding of the lectin to viral carbohydrates. The mammalian C-type lectin family includes conglutinin, mannose-binding protein, and surfactant proteins A and D. These lectins may be important constituents of the initial host response to IAV, by inhibiting IAV infectivity directly, causing viral aggregation, and acting as opsonins to enhance phagocyte responses to the virus.
Animals↗
Human mannose-binding protein functions as an opsonin for influenza A viruses.
Influenza A viruses (IAVs) cause substantial morbidity and mortality in yearly epidemics, which result from the ability of the virus to alter the antigenicity of its envelope proteins. Despite the rapid replication of this virus and its ability to infect a wide variety of cell types, viremia is rare and the infection is generally limited to the upper respiratory tract. The preimmune host defense response against IAV is generally, therefore, successful. We have previously provided (and summarized) evidence that neutrophils contribute to defense against IAV, although neutrophil dysfunction and local tissue damage may be less salutory byproducts of this response. Here we provide evidence that the serum lectin mannose-binding protein directly inhibits hemagglutinin activity and infectivity of several strains of IAV. In addition mannose-binding protein acts as an opsonin, enhancing neutrophil reactivity against IAV. Opsonization of IAV by mannose-binding protein also protects the neutrophil from IAV-induced dysfunction. These effects are observed with physiologically relevant concentrations of mannose-binding protein. Two different allelic forms of recombinant mannose-binding protein are found to have similar effects. We believe, on the basis of these data, that mannose-binding protein alone and in conjunction with phagocytic cells is an important constituent of natural immunity (i.e., preimmune defense) against IAV.
Acute-Phase Proteins↗
Influenza A virus binding to human neutrophils and cross-linking requirements for activation.
Although neutrophils are not viewed as a principal defense against influenza A virus (IAV) infection, their interactions are both complex and clinically relevant. Activation of the neutrophil is distinctive from that described for chemoattractants. To more fully characterize the pathway by which IAV stimulates the human neutrophil, we have examined its binding characteristics. First, inhibition studies with various sialic acid-containing and sialic-free sugars showed that IAV binds to sialic acid residues and activates receptors distinct from those used by Concanavalin-A (Con-A) and formyl-methionyl-leucyl-phenylalanine (FMLP) and that overlap those bound by wheat germ agglutinin (WGA). That viral hemagglutinin (HA) mediates viral binding and activation was shown by preincubating neutrophils with purified monovalent bromelain-released HA (BHA) and showing that IAV-induced membrane depolarization and hydrogen peroxide (H2O2) production were inhibited approximately 95%. However, binding inhibition required significantly higher concentrations of purified HA, suggesting that binding and cell activation have different interactive requirements. Desialation of the neutrophil surface membrane by neuraminidase treatment resulted in a 90.6% +/- 4.4% and 53.1% +/- 8.7% inhibition of IAV activation of neutrophils and viral binding, respectively. Resialation with ganglioside GT1b totally restored viral binding, but did not reverse the inhibition of activation. Thus, although HA was shown to mediate binding and neutrophil activation, viral binding per se was insufficient to stimulate the cell. Having demonstrated the functional role of HA, we sought to establish the mechanism of stimulation. HA in three different forms (BHA, HA-rosettes, and HA-liposomes) failed to activate the cell, although H2O2 production evoked by IAV stimulation was reduced in competitive inhibition studies with each preparation. Upon cross-linking with a monoclonal antibody to HA, activation comparable to that of intact virus was observed. The requirement for cross-linking of functional receptors, as opposed to activation through the neutrophil Fc receptor, was confirmed in experiments using staphylococcal A protein. These studies have shown the chemical specificity of IAV binding to the human neutrophil, the character of the receptor(s) stimulated to activate the IAV-evoked response, and the activation requirement for cross-linking those receptors responsible for stimulating functional responses.
Antibodies, Monoclonal↗
Comparison of influenza A virus and formyl-methionyl-leucyl-phenylalanine activation of the human neutrophil.
Influenza A virus (IAV) activates the human neutrophil, but induces a dysfunctional state as well. Cell activation may contribute to the containment of the virus and/or cause local tissue damage. Certain features of the neutrophil activation response elicited by IAV are distinctive when compared with that triggered by formyl-methyl-leucyl-phenylalanine (FMLP). An atypical respiratory burst response occurs in which hydrogen peroxide, but no superoxide, is formed. This unusual respiratory burst stoichiometry persists despite marked priming of the IAV-induced response. A comprehensive examination of the activation cascade initiated by these stimuli failed to show an explanation for these differences. Both IAV and FMLP comparably stimulate inositol trisphosphate and phosphatidic acid production. The subsequent increase in intracellular calcium (Ca2+i) upon FMLP stimulation was more dependent on extracellular Ca2+ than with IAV activation, but both stimuli induced Ca2+ influx. FMLP and IAV exhibited equal susceptibility to inhibition by protein kinase inhibitors in eliciting the respiratory burst, and actin polymerization occurred in response to each agonist. A possible explanation for the anomalous respiratory burst induced by IAV is that O2- is generated at an intracellular site inaccessible to assay, and/or virus binding to sialic acid constituents of the plasma membrane alters the O2- generating capacity of the respiratory burst oxidase; evidence for each mechanism is offered.
Actins↗
Anomalous features of human neutrophil activation by influenza A virus are shared by related viruses and sialic acid-binding lectins.
Influenza A virus (IAV) causes both activation and deactivation of the human neutrophil, which may, respectively, contribute to host defense against the virus and enhanced susceptibility to bacterial superinfection. We have shown that certain features of neutrophil activation by IAV are distinctive compared with activation by chemoattractants in terms of both the stoichiometry of the respiratory burst response and the signal transduction events that precede it. We here demonstrate that related myxoviruses as well as sialic acid-binding lectins elicit a respiratory burst response similar to that induced by IAV, in which hydrogen peroxide is formed with minimal accompanying superoxide generation. Brief preincubation of neutrophils with these agents fully inhibits subsequent activation by IAV, implying that they are binding to the same surface membrane components as IAV. Preincubation with Limax flavus agglutinin (LFA) does, in fact, substantially reduce binding of radiolabeled IAV to the neutrophil. This lectin, like IAV, both activates and deactivates the neutrophil. As in the case of IAV, LFA-induced activation (1) is mediated via stimulation of phospholipase C, (2) is pertussis toxin insensitive, and (3) entails a lesser contribution of calcium influx than is the case for chemoattractants.
Humans↗
Analyses of exobiological and potential resource materials in the Martian soil.
Potential Martian soil components relevant to exobiology include water, organic matter, evaporites, clays, and oxides. These materials are also resources for human expeditions to Mars. When found in particular combinations, some of these materials constitute diagnostic paleobiomarker suites, allowing insight to be gained into the probability of life originating on Mars. Critically important to exobiology is the method of data analysis and data interpretation. To that end we are investigating methods of analysis of potential biomarker and paleobiomarker compounds and resource materials in soils and rocks pertinent to Martian geology. Differential thermal analysis coupled with gas chromatography is shown to be a highly useful analytical technique for detecting this wide and complex variety of materials.
Chromatography, Gas↗
Cloning and characterization of the mouse neu promoter.
We have isolated a genomic clone containing the mouse neu gene. The 5' end of the mouse neu gene was localized by Southern analysis, subcloned and characterized. DNA sequence analysis revealed that the promoter region is 67% G+C-rich and lacks a TATA box, although a CAAT box is present. By sequence comparison, we identified several consensus recognition sequences for general transcription factors such as Sp1, E4TF1, AP2, OTF-1 and GCF, as well as recognition sequences for RVF, E1A and GTG, which have recently been identified in the rat neu promoter. Functional promoter activity was demonstrated by the ability of the promoter to drive transcription of the bacterial chloramphenicol acetyltransferase gene. Using a series of 5'-end deletion mutants, we have identified multiple positive and negative cis-acting elements that regulate mouse neu gene transcription.
Animals↗
Upper respiratory disease in deployed U.S. Navy shipboard personnel.
A study was conducted to determine the risk of upper respiratory disease among deployed U.S. Navy shipboard personnel. Between January and June 1989, a Patient Encounter Form was used to collect disease information from 10 U.S. Navy ships. Patients with a diagnosis of upper respiratory infection (URI) on initial sick-call visit were used in this study. Information on time spent in various ports and time at sea for each of the 10 ships was also collected. A classification scheme was developed to permit daily estimates of URI rates and to indicate whether the ship was in port or at sea. Of 967 cases of URI, 64.4% occurred while at sea, with an average daily rate of 0.5/1,000 crew members; 35.4% of the cases occurred while in port, with an average daily rate of 0.4/1,000 crew members. There was an increase in URI rates after 9 days at sea or in port. These data suggest that there are defined periods of increased transmission of upper respiratory infections aboard ships, both at sea and in port.
Humans↗
Membrane-permeable luciferin esters for assay of firefly luciferase in live intact cells.
Five esters of luciferin were synthesized and compared with native luciferin as substrates for firefly luciferase expressed in live intact mammalian cells. The esters themselves were not substrates for purified luciferase, but four were substrates for a purified esterase and all appeared to be hydrolysed to luciferin within mammalian cells. At a substrate concentration of 0.01 mM, the peak luminescence from the cos cells expressing luciferase was up to 6-fold greater with the esters than with unmodified luciferin. At 0.1 mM, the difference between luciferin and the esters was decreased. The kinetics of the luminescent signal with the different luciferin esters varied significantly, indicating possible differences in the rates of uptake, breakdown and enzyme inhibition. The esters did not support luminescence from Escherichia coli cells expressing firefly luciferase, suggesting a lack of appropriate esterase activity in this particular strain. The esters could be useful for the assay of luciferase expression in intact mammalian cells when luciferin levels are limiting, for example in tissues, and in plants. Alternative luciferin derivatives may allow further improvements in sensitivity.
Animals↗
Encephalitis in two porcupines due to Baylisascaris larval migration.
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Animals↗
Morbidity and mortality in U.S. Navy personnel from exposures to hazardous materials, 1974-85.
A total of 1,371 hospitalizations and 136 deaths occurred in U.S. Navy enlisted personnel from 1974 to 1985 as a result of exposures to hazardous materials. Exposures to various gas fumes and vapors accounted for the largest percentage of all hospitalizations (38%), and the second largest percentage of deaths (20.6%). The most frequent cause of death was from carbon monoxide poisoning; nearly 74% of all reported deaths were attributed to this gas. Hospitalization rates were highest among the 17- to 19-year-olds across all race categories. This may be attributed either to their lack of experience and knowledge concerning the safe handling of these materials, or perhaps a disproportionate number of 17- to 19-year-olds are given tasks which put them at higher risk. The Navy occupations showing the highest risk for various exposures to hazardous materials were Utilitiesman, Hull Maintenance Technician, and Boatswain's Mate. It is the inhalation of these compounds which poses the greatest health risk to personnel both onshore and aboard ships.
Adolescent↗
Characterization of influenza A virus activation of the human neutrophil.
Neutrophil dysfunction consequent to influenza A virus infection has been described in vivo and in vitro and may contribute to the serious bacterial sequelae which occur in influenza-infected hosts. On the premise that such dysfunction may represent a form of "deactivation," we sought to characterize neutrophil activation by the virus in comparison with other agonists. The virus induces a respiratory burst in which H2O2 (but not O2-) are formed. Preceding the respiratory burst, a rise in intracellular calcium (Ca2+i) is noted, but both responses are nearly independent of extracellular Ca2+, unlike those elicited by the other well-characterized Ca2+-dependent agonists, formyl-methyl-leucyl-phenylalanine (FMLP), or Concanavalin-A (Con-A). The Ca2+ increase is paralleled by IP3 generation, implying that it is the result of phospholipase C (PLC) activation. The virus also elicits neutrophil membrane depolarization, which is independently mediated from the Ca2+ increase and respiratory burst and may reflect protein kinase C (PK-C) activation. Virus-induced responses are insensitive to pertussis toxin (PT); cholera toxin does inhibit these responses but in a nonspecific manner. Thus, although influenza virus activates PLC in neutrophils, it does so in a PT-insensitive manner and does not elicit or require a discernible Ca2+ influx to generate a respiratory burst response. In aggregate, the data indicate that influenza A virus activates neutrophils in a manner distinct from that of other well-described neutrophil agonists. These results illustrate the diversity of neutrophil activation mechanisms and support the notion that further characterization of this pathway may facilitate understanding of neutrophil dysfunction induced by the virus.
Calcium↗
Incidence of leukemia in occupations with potential electromagnetic field exposure in United States Navy personnel.
Leukemia is the fourth most commonly occurring cancer in the United States population between the ages of 17 and 34 years, an age group heavily represented in the US Navy. Historical computerized military career records maintained at the Naval Health Research Center, San Diego, California, were used to determine person-years at risk (total, 4,072,502 person-years) by demographic characteristics and occupation for active-duty naval personnel during 1974-1984. Computerized inpatient medical records were searched for first hospitalizations for leukemia. Cases of leukemia (n = 102) were verified by using pathology reports or Navy Medical Board or Physical Evaluation Board findings. For comparisons, age-adjusted incidence rates and standardized incidence ratios were calculated by using rates for the US population provided by the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. The overall age-adjusted incidence rate of leukemia in active-duty naval personnel was found to be very close to that of the Surveillance, Epidemiology, and End Results program population (6.0 vs. 6.5 per 100,000 person-years). Only one occupation, electrician's mate, emerged with a borderline statistically significant excess risk of leukemia (standardized incidence ratio compared with the Surveillance, Epidemiology, and End Results program population = 2.4, 95% confidence interval 1.0-5.0). This finding is intriguing in the light of several studies showing an excess risk of leukemia associated with exposure to electromagnetic fields.
Adolescent↗
Human neutrophil stimulation by influenza virus: relationship of cytoplasmic pH changes to cell activation.
We have previously demonstrated that influenza A virus (IAV) stimulates the human neutrophil through phospholipase C activation. With the use of the fluorescent indicator 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF), cytoplasmic acidification and subsequent alkalinization are shown to accompany this activation. These responses are not inhibited by pertussis toxin (PT). The alkalinization is mediated largely *but not entirely) by the Na(+)-H+ antiporter and is not initiated, or modulated, by the IAV-induced cytosolic Ca2+ (Cai2+) rise. Rather, protein kinase C (PKC) is likely the mediator of cell alkalinization, based on studies using the PKC inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7). The acidification can be dissociated from the alkalinization response, which is also independent of Cai2+ fluxes and of PKC. Both pHi responses can be dissociated from the respiratory burst. Cytosolic alkalinization and acidification seem to reflect two independently mediated responses of the activated neutrophil, the former resulting ultimately from phospholipase activation and the latter from other activities that are not yet fully characterized.
Calcium↗
An unusual case of traumatic pericarditis in a cow.
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Actinomycosis↗
Orbital neoplasia with enophthalmos in a cat.
A 9-year-old cat was evaluated for left-sided enophthalmos and protrusion of the third eyelid. A primary orbital fibrosarcoma was diagnosed. During the orbital exploration, normal periorbital fascia could not be identified in the lateral and ventral region, thus accounting for the enophthalmos.
Animals↗