347 results on '"M. M Stevenson"'
Search Results
2. Dyserythropoiesis and severe anaemia associated with malaria correlate with deficient interleukin-12 production
- Author
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M M Stevenson and K Mohan
- Subjects
medicine.medical_treatment ,Spleen ,Hematology ,Biology ,biology.organism_classification ,Plasmodium chabaudi ,Pathogenesis ,Cytokine ,medicine.anatomical_structure ,Immunology ,Interleukin 12 ,medicine ,Erythropoiesis ,Bone marrow ,Dyserythropoietic anemia - Abstract
Complex cytokine interactions occur during blood-stage malaria which offer a unique opportunity to study their influence on the pathogenesis of malarial anaemia. Plasmodium chabaudi AS susceptible A/J mice experience severe and fatal anaemia whereas resistant C57BL/6 (B6) mice survive following moderate anaemia. In this study we analysed the role of IL-12 in erythropoiesis and tested whether the levels of IL-12 produced in these mice correlated with the extent of anaemia. In vitro, IL-12 significantly enhanced the numbers of erythroid burst (BFU-E) and colony forming units (CFU-E) in bone marrow and spleen cells from normal and day 7 infected A/J and B6 mice. Despite the presence of IL-12 in vitro, the level of splenic erythropoiesis in infected A/J mice was significantly lower than in B6 mice. Moreover, sera from infected B6 mice, but not A/J mice, significantly up-regulated erythropoiesis in vitro and this enhancement correlated with several fold higher levels of IL-12 in the sera of B6 compared to A/J mice. Furthermore, the erythropoietic potentiating effect of sera from infected B6 mice was abrogated following depletion of IL-12. Taken together, these findings suggest that defective IL-12 production in A/J mice during the early course of infection may result in fatal anaemia.
- Published
- 1998
3. Natural killer cell cytokine production, not cytotoxicity, contributes to resistance against blood-stage Plasmodium chabaudi AS infection
- Author
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K Mohan, P Moulin, and M M Stevenson
- Subjects
Immunology ,Immunology and Allergy - Abstract
Our recent study showed that IL-12 treatment of susceptible A/J mice induces Th1-mediated, protective immunity against lethal blood-stage Plasmodium chabaudi AS infection. To further understand the mechanism of this protection, we examined NK cell cytotoxic (NKCC) and cytokine secretory functions in untreated and IL-12-treated A/J mice, along with resistant C57BL/6 (B6) mice. Normal A/J mice receiving six daily doses of 0.1 microg IL-12 exhibited significant increases in NKCC in total spleen cell populations. Defective NKCC evident in vitro in enriched NK cells from infected A/J mice was corrected by addition of 10 ng/ml IL-12 and was comparable with that seen in B6 mice. In vivo and in vitro analyses revealed that enriched NK cells from day 6 infected A/J mice were defective not only in NKCC, but also in IFN-gamma, and to a certain extent, TNF-alpha secretion, which could also be corrected by IL-12 treatment. Depletion of NK cells from resistant B6 mice resulted in a more severe course of infection, while NK cell-depleted, IL-12-treated A/J mice had significantly higher parasitemia, as well as 100% mortality, suggesting the importance of NK cells in IL-12-mediated protection. NKCC-defective bg/bg mice produced optimum IFN-gamma and TNF-alpha and recovered from infection similar to bg/+ controls; in vivo depletion of these cytokines resulted in significantly higher parasitemia early in infection. Based on these results, we conclude that IFN-gamma, and possibly TNF-alpha, secretion by NK cells during early infection plays a major role in protective immunity to blood-stage malaria.
- Published
- 1997
4. IL-12-induced protection against blood-stage Plasmodium chabaudi AS requires IFN-gamma and TNF-alpha and occurs via a nitric oxide-dependent mechanism
- Author
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M M Stevenson, M F Tam, S F Wolf, and A Sher
- Subjects
Immunology ,Immunology and Allergy - Abstract
The effects of IL-12 administration on the development of protective immunity to blood-stage Plasmodium chabaudi AS were analyzed. Treatment of susceptible A/J mice on the day of infection and for 5 days postinfection with various doses 0.025-0.3 microgram) of rIL-12 significantly decreased the peak parasitemia level, but only treatment with 0.1 microgram resulted in increased survival. Treatment of resistant B6 mice with 0.1 microgram of rIL-12 using the same regimen also significantly decreased the peak parasitemia level, but 40% of the animals died. Treatment of these mice with anti-IL-12 mAb resulted in a more severe course of infection, but survival was not significantly altered. The mechanism of IL-12-induced resistance was examined in A/J mice during infection. Compared with spleen cells from untreated mice, cells from IL-12-treated mice produced significantly higher levels of IFN-gamma spontaneously as well as in response to Con A or Ag stimulation on day 7 postinfection. Significantly higher levels of INF-gamma and TNF-alpha were found in the sera of IL-12-treated mice, which correlated with high levels of the nitric oxide (NO) metabolite, NO3-. Furthermore, CD4+T cell depletion was found to abrogate IL-12-induced resistance. Administration of neutralizing mAb against IFN-gamma or TNF-alpha to IL-12-treated mice showed that simultaneous depletion of both cytokines resulted in 100% mortality. The role of NO was investigated by administration of aminoguanidine, a selective inhibitor of cytokine-inducible nitric oxide synthase, to IL-12-treated mice. Significantly increased mortality was observed following treatment twice daily with 9 mg of aminoguanidine, but there was no effect on parasitemia. In conclusion, these results demonstrate that IL-12 regulates the development of resistance to P. chabaudi AS via a CD4+ Th1 response, which involves the cytokines IFN-gamma and TNF-alpha, and is in part NO dependent. Therefore, IL-12, given in the appropriate dose, may be useful in the induction of protective immunity to blood-state malaria.
- Published
- 1995
5. Caspase-12 deficiency enhances cytokine responses but does not protect against lethal Plasmodium yoelii 17XL infection
- Author
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J, Miu, M, Saleh, and M M, Stevenson
- Subjects
Mice, Inbred C57BL ,Mice, Knockout ,Mice ,Liver ,Animals ,Cytokines ,Female ,Plasmodium yoelii ,Parasitemia ,Survival Analysis ,Caspase 12 ,Malaria - Abstract
To investigate the effect of caspase-12 deficiency on IFN-γ- independent control of blood-stage malaria, we compared lethal Plasmodium yoelii 17XL infection in wild-type C57BL ⁄ 6J and caspase-12-/-mice. Infected caspase-12-/- mice exhibited higher parasitaemia than WT mice on days 8 and 9 post-inoculation, but all WT and caspase-12-/- mice succumbed by day 10. In addition, infected caspase-12-/-mice had significantly elevated levels of IFN-γ, TNF, IL-18,and IL-10 in sera compared to infected WT mice. At the terminal stage of disease, there were no differences in cytokine levels in the tissues of infected WT and caspase-12-/- mice. However, liver pathology was more severe in infected caspase-12-/- mice compared to infected WT mice. Together, these findings indicate that although caspase-12 deficiency results in enhanced pro-inflammatory and immunoregulatory cytokine levels in sera during P. yoelii 17XL infection, these responses are not essential for protection against lethal malaria infection.
- Published
- 2010
6. Updated NCEP guidelines set new decision points for managing dyslipidemia
- Author
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M M, Stevenson
- Subjects
Adult ,Male ,Risk ,Practice Guidelines as Topic ,Age Factors ,Humans ,Coronary Disease ,Female ,Hyperlipidemias ,Middle Aged ,Life Style ,Aged ,Hypolipidemic Agents - Published
- 2001
7. Smoking and cardiovascular disease
- Author
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R J, Marshall and M M, Stevenson
- Subjects
Adult ,Male ,Adolescent ,Cardiovascular Diseases ,Risk Factors ,Smoking ,Humans ,Female ,Smoking Cessation ,Middle Aged ,West Virginia ,Aged - Published
- 2001
8. Mouse models of chronic lung infection with Pseudomonas aeruginosa: models for the study of cystic fibrosis
- Author
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P K, Stotland, D, Radzioch, and M M, Stevenson
- Subjects
Lung Diseases ,Mice, Knockout ,Disease Models, Animal ,Mice ,Cystic Fibrosis ,Chronic Disease ,Pseudomonas aeruginosa ,Animals ,Cystic Fibrosis Transmembrane Conductance Regulator ,Cytokines ,Pseudomonas Infections ,Lung ,Forecasting - Abstract
The discovery of the CFTR gene in 1989 has lead to rapid progress in understanding the molecular basis of cystic fibrosis (CF) and the biological properties of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. However, more than 10 years later, recurrent lung infections with Pseudomonas aeruginosa, which lead to chronic lung disease and eventual respiratory failure, remain the major cause of morbidity and mortality among CF patients. A distinguishing feature of lung disease in CF is an exaggerated and persistent inflammatory response, characterized by the accumulation of excessive numbers of neutrophils and dysregulated cytokine production. The events leading to the establishment of lung infection with P. aeruginosa, especially the inflammatory and immunological events, and the relation between the CF defect and infection, remain largely undefined. Progress in this area has been hampered by the lack of a suitable animal model. An exciting achievement in the past few years has been the development of a number of variants of CFTR-deficient mice which exhibit defective cAMP-mediated Cl(-) conductance and have a range of clinical phenotypes from mild to severe. In parallel, a model of chronic P. aeruginosa lung infection has been established in genetically and immunologically well-defined inbred mouse strains which differ in susceptibility to this infection in the lung. BALB/c mice are resistant, while DBA/2 mice are extremely susceptible, with high mortality within 3 days of infection. C57BL/6 and A/J mice are relatively susceptible and experience low mortality. Furthermore, the bacterial load correlates with the magnitude and quality of the inflammatory response in the infected lungs of BALB/c and C57BL/6 mice. Although results of infection studies in CFTR-deficient mice have been variable, C57BL/6-Cftr(m1UNC)/Cftr(m1UNC) knockout mice compared to littermate control mice are highly susceptible to chronic P. aeruginosa infection in the lung. The availability of CFTR knockout mice and non-CF inbred mice differing in susceptibility to chronic P. aeruginosa infection offers useful tools for progress in understanding the genesis of chronic P. aeruginosa infection and the ensuing inflammation in the CF lung, as well as the relation between the CF defect and infection. Information generated from these studies will provide the rationale for the development of novel immunomodulatory measures capable of ameliorating or modulating the chronic inflammation associated with CF lung disease.
- Published
- 2000
9. Characterization of chronic bronchopulmonary Pseudomonas aeruginosa infection in resistant and susceptible inbred mouse strains
- Author
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M. M. Stevenson, G. J. Snipes, and Mifong Tam
- Subjects
Pulmonary and Respiratory Medicine ,Lung Diseases ,food.ingredient ,Time Factors ,Intratracheal instillation ,Clinical Biochemistry ,Inflammation ,Mice, Inbred Strains ,Neutrophilic inflammation ,medicine.disease_cause ,Microbiology ,Mice ,food ,Species Specificity ,Weight Loss ,medicine ,Leukocytes ,Agar ,Animals ,Pseudomonas Infections ,Molecular Biology ,Lung ,Mice, Inbred BALB C ,Strain (chemistry) ,biology ,Pseudomonas aeruginosa ,Cell Biology ,biology.organism_classification ,Immunity, Innate ,Death ,Mice, Inbred C57BL ,Disease Susceptibility ,medicine.symptom ,Bacteria ,Clearance - Abstract
Chronic bronchopulmonary Pseudomonas aeruginosa infection, initiated by intratracheal instillation of 1 to 2 x 10(5) colony-forming units of a mucoid strain of bacteria trapped in agar beads, was characterized in resistant BALB/c mice and susceptible C57BL/6 (B6) mice through 28 d postinfection. B6 mice experienced a more severe infection than BALB/c mice as evidenced by significantly higher mortality and significantly greater weight loss during the first 14 d. Furthermore, B6 mice had significantly higher numbers of bacteria in the lungs through 21 d after infection. Overall, only 22% of these hosts cleared the infection. In contrast, 67% of BALB/c mice cleared the infection. These differences between resistant and susceptible mice were found to correlate with histopathologic differences in the type of inflammation and the extent of tissue damage. An acute, predominantly neutrophilic inflammation and extensive tissue damage were apparent in the lungs of susceptible B6 mice, whereas chronic, granulomatous inflammation and little or no tissue damage were visible in resistant BALB/c mice. The finding of acute inflammation in the lungs of infected B6 mice was confirmed by fluorescence-activated cell sorter (FACS) analyses, which demonstrated that these mice had significantly greater proportions of polymorphonuclear neutrophils in the lungs on Days 7 and 14 after infection than did BALB/c mice. FACS analyses also revealed significant and similar increases in CD3(+) lung cells in both strains as the infection progressed. The CD4/CD8 ratio was significantly greater in BALB/c mice by 21 d after infection when the majority of these animals, but not B6 mice, had cleared the infection.
- Published
- 1999
10. In vivo IL-12 production and IL-12 receptors beta1 and beta2 mRNA expression in the spleen are differentially up-regulated in resistant B6 and susceptible A/J mice during early blood-stage Plasmodium chabaudi AS malaria
- Author
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H, Sam and M M, Stevenson
- Subjects
Base Sequence ,Mice, Inbred A ,Reverse Transcriptase Polymerase Chain Reaction ,Receptors, Interleukin-12 ,Receptors, Interleukin ,Th1 Cells ,Interleukin-12 ,Malaria ,Up-Regulation ,Mice, Inbred C57BL ,Interferon-gamma ,Kinetics ,Mice ,Species Specificity ,Plasmodium chabaudi ,Animals ,RNA, Messenger ,Spleen ,DNA Primers - Abstract
As previously reported, blood-stage Plasmodium chabaudi AS malaria is lethal by days 10-12 postinfection in susceptible A/J mice that mount an early, predominantly Th2 response. In contrast, resistant C57BL/6 (B6) mice clear the infection by 4 wk with an early Th1 response. In this study, we analyzed in vivo production of IL-12, a potent Th1-inducing cytokine, during the first 5 days after P. chabaudi AS infection in these mice. By day 2, serum IL-12 p70 levels were significantly increased in B6 mice over basal levels and were also significantly higher compared with A/J mice that showed no significant changes in serum p70 levels after infection. Splenectomy of resistant B6 mice before infection demonstrated that the spleen is the major source of systemic IL-12 in these hosts. Splenic mRNA levels of both p40 and p35 were significantly higher in A/J mice; however, the ratios of p40/p35 mRNA levels were similarly up-regulated in both strains. Furthermore, B6 but not A/J mice showed significant up-regulation of splenic IL-12R beta2 mRNA over basal levels by days 3 and 4, coincident with sustained up-regulation of splenic IFN-gamma mRNA levels on days 3-5. However, IL-12R beta1 mRNA levels in the spleen were similarly up-regulated in both mouse strains by day 3. Taken together, these data suggest that high systemic IL-12 production, accompanied by an early and sustained up-regulation of both IL-12R beta1 and beta2 mRNA levels in the spleen, as occurs in resistant B6 mice, appears to preferentially induce protective Th1 responses against blood-stage malaria.
- Published
- 1999
11. Dyserythropoiesis and severe anaemia associated with malaria correlate with deficient interleukin-12 production
- Author
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K, Mohan and M M, Stevenson
- Subjects
Erythroid Precursor Cells ,Mice ,Plasmodium chabaudi ,Animals ,Anemia ,Interleukin-12 ,Cell Division ,Hematopoiesis ,Malaria - Abstract
Complex cytokine interactions occur during blood-stage malaria which offer a unique opportunity to study their influence on the pathogenesis of malarial anaemia. Plasmodium chabaudi AS susceptible A/J mice experience severe and fatal anaemia whereas resistant C57BL/6 (B6) mice survive following moderate anaemia. In this study we analysed the role of IL-12 in erythropoiesis and tested whether the levels of IL-12 produced in these mice correlated with the extent of anaemia. In vitro, IL-12 significantly enhanced the numbers of erythroid burst (BFU-E) and colony forming units (CFU-E) in bone marrow and spleen cells from normal and day 7 infected A/J and B6 mice. Despite the presence of IL-12 in vitro, the level of splenic erythropoiesis in infected A/J mice was significantly lower than in B6 mice. Moreover, sera from infected B6 mice, but not A/J mice, significantly up-regulated erythropoiesis in vitro and this enhancement correlated with several fold higher levels of IL-12 in the sera of B6 compared to A/J mice. Furthermore, the erythropoietic potentiating effect of sera from infected B6 mice was abrogated following depletion of IL-12. Taken together, these findings suggest that defective IL-12 production in A/J mice during the early course of infection may result in fatal anaemia.
- Published
- 1999
12. Interleukin-12 corrects severe anemia during blood-stage Plasmodium chabaudi AS in susceptible A/J mice
- Author
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K, Mohan and M M, Stevenson
- Subjects
Mice ,Plasmodium chabaudi ,Animals ,Anemia ,Disease Susceptibility ,Interleukin-12 ,Injections, Intraperitoneal ,Recombinant Proteins ,Malaria - Abstract
The in vivo role of interleukin (IL)-12 in correcting anemia and the underlying defect in erythropoiesis in Plasmodium chabaudi AS-susceptible A/J mice was examined. Six daily intraperitoneal injections of 0.1 microg IL-12 in A/J mice, beginning on the day of infection, rapidly and significantly enhanced bone marrow and splenic erythropoiesis as demonstrated by marked increases in early and late committed erythroid progenitors, the erythroid burst (BFU-E) and colony-forming units (CFU-E), respectively, compared with control mice. The most dramatic effect of IL-12 treatment was a sevenfold increase in the number of splenic CFU-E on day 7 postinfection, compared with untreated, infected A/J mice. Treatment with IL-12 also caused significant increases in hematocrit levels, erythrocyte counts, percentage of reticulocytes, spleen cellularity, and frequencies of BFU-E and CFU-E in the bone marrow and spleen of A/J mice during infection. The frequency of BFU-E in the peripheral blood of these mice was also significantly increased, suggesting enhanced mobilization of precursor cells to the spleen as well as increased production of erythroid precursors in this organ. Consistent with previous observations using higher doses, 0.1 microg IL-12 administered daily for 6 days to normal A/J mice significantly decreased bone marrow erythropoiesis and significantly increased splenic erythropoiesis. However, the influence of IL-12 on erythropoiesis was much more pronounced during ongoing malaria infection. These results suggest a role for IL-12 during blood-stage malaria in not only enhancing the development of protective immunity but also in alleviating malaria-induced anemia by increasing the number of erythroid precursors and enhancing the expansion of committed erythroid progenitors.
- Published
- 1998
13. Audit of a policy to improve communication with patients who default
- Author
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M Huengsberg, M M Stevenson, and K W Radcliffe
- Subjects
Adult ,Male ,medicine.medical_specialty ,Medical Audit ,Adolescent ,business.industry ,Communication ,Public Health, Environmental and Occupational Health ,Dermatology ,Audit ,Audit plan ,Middle Aged ,Surgery ,Infectious Diseases ,Joint audit ,Medicine ,Humans ,Patient Compliance ,Pharmacology (medical) ,Information technology audit ,Operations management ,Female ,business ,Aged - Published
- 1997
14. Nitric oxide expression in the spleen, but not in the liver, correlates with resistance to blood-stage malaria in mice
- Author
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P, Jacobs, D, Radzioch, and M M, Stevenson
- Subjects
Male ,Nitrates ,Mice, Inbred A ,Molecular Sequence Data ,Nitrous Oxide ,Nitric Oxide ,Guanidines ,Immunity, Innate ,Malaria ,Mice, Inbred C57BL ,Mice ,Liver ,Plasmodium chabaudi ,Animals ,Female ,RNA, Messenger ,Enzyme Inhibitors ,Nitric Oxide Synthase ,Spleen - Abstract
The production and function of nitric oxide during the early phase of blood-stage infection with Plasmodium chabaudi AS was analyzed using two inbred strains of mice that differ in the level of resistance to this parasite. Northern blot analysis of in vivo expression of inducible nitric oxide synthase (iNOS) revealed that early during infection resistant C57BL/6 mice, which clear the infection by 4 wk, have higher levels of iNOS mRNA in the spleen than susceptible A/J mice. In contrast, susceptible A/J mice have significantly increased levels of iNOS mRNA in the liver later in the course of infection just before death occurs. Splenic macrophages recovered from resistant C57BL/6 mice on day 7 postinfection express iNOS mRNA which is up-regulated following overnight stimulation of the cells with LPS. Furthermore, during the first week postinfection, splenic macrophages recovered from resistant hosts produce significantly higher levels of nitrite (NO2-) in vitro in response to LPS than similarly stimulated macrophages from susceptible A/J mice. Increased levels of nitrate (NO3-) were only detected in serum of resistant C57BL/6 mice at the time of peak parasitemia. Treatment with the iNOS inhibitor, aminoguanidine, reduced NO3- levels in serum of C57BL/6 mice and eliminated resistance of these hosts to P. chabaudi AS malaria without affecting parasitemia. These results demonstrate that the ability to produce high amounts of nitric oxide (NO) early during infection with blood-stage P. chabaudi AS correlates with resistance, but that NO may not be involved in parasite killing. Moreover, the tissue site of NO production, that is, spleen vs liver, appears to be critical and correlates with resistance vs susceptibility to P. chabaudi AS malaria, respectively.
- Published
- 1995
15. Preventing pelvic infection after abortion
- Author
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K W Radcliffe and M M Stevenson
- Subjects
Sexually transmitted disease ,medicine.medical_specialty ,Gonorrhea ,Sexually Transmitted Diseases ,Dermatology ,Abortion ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Risk Factors ,Pelvic inflammatory disease ,medicine ,Prevalence ,Humans ,Mass Screening ,Pharmacology (medical) ,030212 general & internal medicine ,Gynecology ,030219 obstetrics & reproductive medicine ,Chlamydia ,business.industry ,Obstetrics ,Public Health, Environmental and Occupational Health ,Antibiotic Prophylaxis ,medicine.disease ,Infectious Diseases ,Abortion, Legal ,Female ,Bacterial vaginosis ,Chlamydia trachomatis ,business ,Pelvic Infection ,Pelvic Inflammatory Disease - Abstract
Pelvic infection is the commonest complication of legal abortion. The presence of lower genital tract infections increases the risk of complications, and women requesting abortion are at significant risk of harbouring sexually transmitted diseases (STD). Prophylactic antibiotic treatment can decrease the rate of post-abortal sepsis, but the optimum regime is unclear. In particular, patients with Chlamydia trachomatis infection, and bacterial vaginosis would appear to be at increased risk, and detection and treatment of these conditions can lower this risk. The opportunity to screen and treat for STD presents itself in this setting, allowing patients and their sexual contacts to benefit, with a decrease in the infected pool in the community.Induced abortion is one of the most frequent surgical procedures in the UK. Even though it is considered safe, it sometimes has complications and long-term sequelae. Pelvic inflammatory disease (PID) is the most prevalent complication and can lead to chronic pelvic pain, pain during intercourse, infertility, and a higher risk of ectopic pregnancy. Chlamydia trachomatis is perhaps the leading etiologic agent for PID among women who have undergone induced abortion and who develop PID. Gonorrhea is another major etiologic agent for PID. Strategies used to try to reduce pelvic infection revolve around administration of antibiotic prophylaxis based on demographic features and on the presence of certain organisms in the genital tract that may increase their risk (e.g., C. trachomatis and Neisseria gonorrhoeae) and universal antibiotic prophylaxis for all women undergoing abortion. Most of the literature suggests that antibiotic prophylaxis does provide some protection against PID but does not clearly indicate who should be screened and for which pathogens and who should be treated and with which antibiotics. Demographic features useful for identifying who should receive antibiotic prophylaxis are: a history of PID, single status, nulliparity, and youth (especially reliable for chlamydial infection). Screening for bacterial vaginosis involves diagnosis based on 3 of 4 criteria: characteristic vaginal discharge, positive amine test, raised vaginal pH, and the presence of clue cells on microscopy of wet or stained preparations of vaginal discharge. Since C. trachomatis is the most important pathogen, drugs sensitive to it should be administered: tetracyclines and erythromycin. Screening women seeking abortion for sexually transmitted diseases (STDs) provides an opportunity to educate them about STDs and treatment compliance and to contact their partners for investigation, treatment, and contact-tracing to reduce the STD-infected pool in the community.
- Published
- 1995
16. Guidelines for the use of blood transfusions
- Author
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M K, Stephens, M M, Stevenson, M B, Taylor, C L, Beall, C A, Heiskell, and W, Mossburg
- Subjects
Blood Transfusion, Autologous ,Risk Factors ,Blood Group Incompatibility ,Practice Guidelines as Topic ,Humans ,Anemia ,HIV Infections ,Erythrocyte Transfusion ,Hepatitis B ,Hepatitis C - Abstract
Over 11 million units of red blood cells are transfused each year in the United States at a cost of over $2 billion. This paper reviews the indications for and the risks of red blood cell transfusions, and provides guidelines for transfusions in both surgical and non-surgical settings.
- Published
- 1995
17. Blood transfusion alters the course and outcome of Plasmodium chabaudi AS infection in mice
- Author
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G S Yap and M M Stevenson
- Subjects
Mice, Inbred C57BL ,Mice ,Infectious Diseases ,Plasmodium chabaudi ,Immunology ,parasitic diseases ,Animals ,Parasitology ,Anemia ,Blood Transfusion ,Microbiology ,Malaria ,Research Article - Abstract
The importance of severe anemia in the mortality of susceptible A/J mice during blood-stage Plasmodium chabaudi AS infection was assessed. Blood transfusion during and 2 to 3 days after peak parasitemia rescued 90% of susceptible mice from severe anemia and death and allowed these mice to clear the infection and acquire immunity to reinfection. However, blood transfusion prolonged the patency of the infection for up to 5 days after peak parasitemia. Blood transfusions in resistant C57BL/6 mice produced an identical effect, that is, prolongation of the patency of parasitemia. In addition, blood transfusion increased the numbers of gametocytes in both mouse strains. In both strains of mice, the rapid reduction in parasitemia, which occurs during crisis, was associated with the development of moderate levels of anemia. The possible mechanisms for the modulation of parasitemia by blood transfusion and the implications of the present observations for our understanding of the events which occur during crisis are discussed. It is proposed that parasitologic crisis is induced and/or maintained by physiological alterations associated with anemia.
- Published
- 1994
18. Review: cytokines and malaria
- Author
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M M, Stevenson, M, Nowotarski, and G, Yap
- Subjects
Lymphokines ,Plasmodium ,Tumor Necrosis Factor-alpha ,Interleukins ,Monokines ,Animals ,Cytokines ,Humans ,Interferons ,Malaria - Abstract
Malaria, which is caused by hemoprotozoan parasites of the genus Plasmodium, has once again reached epidemic proportions. The resurgence of malaria has occurred because the parasite has developed resistance to the anti-malarial drugs and the mosquito vector has developed resistance to the insecticides. Added to these impediments is the problem that, in spite of intense efforts by researchers world-wide, there is yet no effective anti-malarial vaccine. Our lack of knowledge concerning the exact mechanism of the host immune response to infection with Plasmodium parasites has contributed significantly to the lack of an effective and safe vaccine. The role of an antibody-independent, cell-mediated mechanism which can result in the generation of soluble mediators or cytokines by T lymphocytes and macrophages in host defense against blood stage malaria is being actively investigated in humans and in mice with malaria. With the availability of recombinant lymphokines and monokines and neutralizing antibodies against these reagents it is now possible to determine the role of cytokines in the development of protective anti-malarial immunity. In this review, we discuss recent evidence from human studies and experimental murine models concerning the possible roles of cytokines in malaria.
- Published
- 1990
19. Erratum: Incremental expression of Tlr4 correlates with mouse resistance to Salmonella infection and fine regulation of relevant immune genes
- Author
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M-F Roy, L Larivière, R Wilkinson, M Tam, M M Stevenson, and D Malo
- Subjects
Immunology ,Genetics ,Genetics (clinical) - Published
- 2006
20. Genetic linkage of resistance to Listeria monocytogenes with macrophage inflammatory responses
- Author
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M M Stevenson, P A Kongshavn, and E Skamene
- Subjects
Immunology ,Immunology and Allergy - Abstract
The mobilization of adequate numbers of mononuclear phagocytes to inflammatory foci was measured in Listeria-resistant and Listeria-sensitive mice. Resistant strains, such as B10.A, were found to have a 2- to 3-fold greater accumulation of peritoneal macrophages after i.p. treatment with a variety of nonspecific inflammatory stimuli in comparison to sensitive strains, such s A/J. In addition to low macrophage inflammatory responses, A/J mice had fewer resident peritoneal macrophages. Moreover, measurement of chemotaxis in vitro of equal numbers of thioglycollate-induced macrophages showed cells from A/J mice to be less responsive to complement-derived chemotactic factors. Thus, the mononuclear phagocyte systems of resistant B10.A and sensitive A/J mice were quantitatively and qualitatively different. A survey of inbred mouse strains revealed that these differences were not peculiar to A strain mice and that, in general, the level of the in vivo macrophage inflammatory response correlated with the level of resistance to Listeria in a given strain. Like resistance to Listeria, the macrophage inflammatory response was found to be genetically controlled by an autosomal, non-H-2-linked gene(s) expressed as incompletely dominant. Backcross analysis showed genetic linkage of the macrophage inflammatory response with resistance to Listeria. Thus, the results of this study provide formal evidence that the cellular basis of the genetically determined, enhanced resistance to Listeria is an augmented pool size of mononuclear phagocytes, and the prompt mobilization of these cells to foci of infection.
- Published
- 1981
21. Macrophages in resistance to rickettsial infections: genetic analysis of susceptibility to lethal effects of Rickettsia akari infection and development of activated, cytotoxic macrophages in A and B10.a mice
- Author
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M S Meltzer, C A Nacy, M M Stevenson, and E Skamene
- Subjects
Immunology ,Immunology and Allergy - Abstract
Susceptibility to lethal effects of Rickettsia akari varies among mouse strains. Although most strains are resistant, A/J mice are extremely sensitive (10,000-fold difference in LD50 between resistant and sensitive strains). In contrast to most strains of mice, A/J mice also fail to develop activated, tumoricidal macrophages after any of several in vivo or in vitro treatments. Are susceptibility to R. akari and inability to develop activated, cytotoxic macrophages in the A/J strain causally related traits? Genetic analysis of macrophage tumoricidal activity in responsive B10.A and nonresponsive A mice suggested this trait was controlled by a single, autosomal, dominant gene. Among (F1 X A) backcross mice, the traits for defective macrophage cytotoxicity and abnormal accumulation of macrophages during inflammation (a response controlled by a single, autosomal, dominant gene) segregated independently. Genetic analysis of resistance to R. akari in sensitive A and resistant B10.A mice suggested this trait was also controlled by a single, autosomal, dominant gene. Among (F1 X A) backcross mice, however, traits for defective macrophage cytotoxicity and R. akari resistance segregated independently. Thus, development of activated tumoricidal macrophages, accumulation of macrophages at sites of inflammation, and resistance to the lethal effects of R. akari in A and B10.A mice were each controlled by single, autosomal, dominant, non-H-2-linked genes. However, genes for control of macrophage activation for tumoricidal activity and for resistance to lethal effects of R. akari infection are distinct.
- Published
- 1982
22. Macrophage function in tumor-bearing mice: evidence for lactic dehydrogenase-elevating virus-associated changes
- Author
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M M Stevenson, J C Rees, and M S Meltzer
- Subjects
Immunology ,Immunology and Allergy - Published
- 1980
23. Studies of Platelet Aggregation, Plasma Adenosine Diphosphate Breakdown and Blood Coagulation in Magnesium Deficient Calves and Rats
- Author
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I. I Yoder and M. M Stevenson
- Subjects
medicine.medical_specialty ,Platelet aggregation ,business.industry ,Magnesium ,chemistry.chemical_element ,Hematology ,Adenosine diphosphate ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Biochemistry ,Internal medicine ,medicine ,Coagulation (water treatment) ,business - Abstract
SummaryADP-induced platelet aggregation and the breakdown of ADP in platelet-poor plasma of normal and magnesium deficient calves and rats have been studied. There was no statistically significant difference in ADP-induced platelet aggregation between the treated and untreated groups of animals. There was a significant difference in the ADP breakdown in platelet poor plasma of magnesium deficient rats as compared to the untreated animals. The platelet count of the magnesium deficient calves and in the citrated platelet-rich plasma of the magnesium deficient rats was not different from the normal. The thrombin clotting and partial thromboplastin times were significantly shortened in the magnesium deficient calves, but the prothrombin time was not affected. These findings suggest that pathological alterations in the serum magnesium levels that are still compatible with life do not influence adenosine diphosphate-induced platelet aggregation but do affect the breakdown of adenosine diphosphate in the plasma of rats. Just as magnesium administration may produce an anticoagulant effect, so may magnesium depletion produce a procoagulant effect in the blood of animals rendered magnesium deficient by diet. The clinical implications of this are discussed.
- Published
- 1970
24. Modulation of primary antibody responses to sheep erythrocytes in Plasmodium chabaudi-infected resistant and susceptible mouse strains
- Author
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M M Stevenson and E Skamene
- Subjects
Plasmodium ,Erythrocytes ,Mice, Inbred A ,Immunology ,chemical and pharmacologic phenomena ,Spleen ,Microbiology ,Plasmodium chabaudi ,Mice ,Species Specificity ,In vivo ,parasitic diseases ,medicine ,Animals ,Sheep ,biology ,biology.organism_classification ,Primary and secondary antibodies ,Virology ,Immunity, Innate ,Malaria ,Mice, Inbred C57BL ,Infectious Diseases ,medicine.anatomical_structure ,Antibody Formation ,biology.protein ,Parasitology ,Disease Susceptibility ,Research Article - Abstract
The in vivo primary antibody response to sheep erythrocytes (SRBC) was determined in genetically resistant C57BL/6 and susceptible A/J mice during the course of infection with Plasmodium chabaudi. Spleen cells from both strains of mice, immunized with SRBC and infected on the same day, showed significant increases in the number of direct plaque-forming cells. The response of malaria-infected C57BL/6 mice was significantly enhanced in comparison with the responses of both normal C57BL/6 and malaria-infected A/J mice. When mice were immunized at later times in the infection, the level of the response declined in both strains until it was less than 50% of the response of normal mice. Thus, suppression of the primary antibody response to SRBC does not correlate with the outcome of P. chaubaudi infection in genetically resistant and susceptible hosts.
- Published
- 1986
25. AIDS: the significance of anti-HTLV-III antibodies
- Author
-
P A, Robinson, J, Brough, L, Haddy, R B, Belshe, R, Khakoo, and M M, Stevenson
- Subjects
Acquired Immunodeficiency Syndrome ,Humans ,Enzyme-Linked Immunosorbent Assay ,False Positive Reactions ,West Virginia ,Antibodies, Viral ,Deltaretrovirus ,False Negative Reactions ,Retroviridae Infections - Published
- 1985
26. Chromosomal location of the gene determining resistance to Plasmodium chabaudi AS
- Author
-
M M, Stevenson, M N, Nesbitt, and E, Skamene
- Subjects
Mice ,Plasmodium ,Genetic Linkage ,Genes, MHC Class II ,Animals ,Chromosome Mapping ,Mice, Inbred Strains - Published
- 1988
27. Blood transfusion reaction in a patient with immunoglobulin A deficiency
- Author
-
E F, Branigan, M M, Stevenson, and D, Charles
- Subjects
Adult ,Bicarbonates ,Pregnancy ,IgA Deficiency ,Immunologic Deficiency Syndromes ,Humans ,Transfusion Reaction ,Female ,Infusions, Parenteral ,Mannitol ,Methylprednisolone Hemisuccinate ,Anaphylaxis - Abstract
Selective deficiency of serum IgA is the most common immunodeficiency in humans; when immunodeficient individuals receive blood transfusions a severe anaphylactoid reaction can develop. The present report describes such a patient. After the transfusion reaction a hemagglutination inhibition assay revealed that her blood contained less than 1.0 micrograms/ml of IgA and an anti-IgA antibody that reacted with the 2 IgA proteins, isotypes IgA1 and IgA2. Immediately after the reaction the patient's serum anti-IgA antibody titer was 1:16,384, and when reevaluated 5 weeks later it was 1:8000. All 3 of her children were shown to be IgA deficient, and 2 of them had antibodies against IgA2. This type of anaphylactoid reaction can be avoided by transfusing blood from IgA-deficient donors, frozen deglycerolized red cells, or red cells that have been washed several times to extract all IgA proteins.
- Published
- 1983
28. Genetic control of macrophage response to infection
- Author
-
E. Skamene and M. M. Stevenson
- Subjects
Genetics ,Inbred strain ,In vivo ,Environment controlled ,Macrophage ,Recombinant inbred strain ,Biology ,In vitro ,Function (biology) - Abstract
Significant interstrain variations in the expression of numerous elements of the macrophage response to infection, which are commonly observed among inbred mice living in a controlled environment suggest that such traits are genetically controlled. The recent increase in awareness of these inherited variations can be attributed to the expectation that the analysis of such experiments of nature, namely, of the mouse strains with well-defined in vitro ‘macrophage’ defects, may enhance our understanding of the mechanisms underlying certain specific steps of macrophage response as well as of their correlation with in vivo host defense function.
- Published
- 1985
29. Natural resistance to Listeria monocytogenes as a function of macrophage inflammatory response
- Author
-
M M, Stevenson, P A, Kongshavn, and E, Skamene
- Subjects
Inflammation ,Mice ,Species Specificity ,Chemotaxis ,Macrophages ,Animals ,Listeriosis ,Mice, Inbred Strains ,Macrophage Activation ,Listeria monocytogenes ,Crosses, Genetic ,Immunity, Innate - Published
- 1983
30. Macrophage function in tumor-bearing mice: tumoricidal and chemotactic responses of macrophages activated by infection with Mycobacterium bovis, strain BCG
- Author
-
M S, Meltzer and M M, Stevenson
- Subjects
Male ,Mice, Inbred C3H ,Chemotaxis ,Macrophages ,Dose-Response Relationship, Immunologic ,Cell Count ,Neoplasms, Experimental ,Cytotoxicity Tests, Immunologic ,Mycobacterium bovis ,Mice ,BCG Vaccine ,Animals ,Cattle ,Tuberculosis, Bovine - Published
- 1977
31. Pneumatic calf compression, fibrinolysis, and the prevention of deep venous thrombosis
- Author
-
T J, Tarnay, P R, Rohr, A G, Davidson, M M, Stevenson, E F, Byars, and G R, Hopkins
- Subjects
Adult ,Leg ,Equipment and Supplies ,Fibrinolysis ,Pressure ,Humans ,Middle Aged ,Thrombophlebitis ,Aged - Abstract
In a previous pilot study that did not reach statistical significance, intermittent single-leg pneumatic compression appeared effective in reducing the incidence of calf vein thrombosis not only in the pumped calf but also in the unpumped leg in 37 patients, using the 125I-fibrinogen (Abbott Laboratories) technique. The present study was undertaken to investigate mechanical induction of local and systemic fibrinolysis. The euglobulin lysis time in the arm venous effluent was determined in five volunteers before and after unilateral arm compression for 1/2 hour. Shortening averaged 19% (not significant). The experiment was repeated using bilateral calf-length boots with femoral vein sampling. Euglobulin lysis decreased 22% (P0.001). To uncover possible systemic effects, the protocol was altered using calf boots with sampling from the arm. The euglobulin lysis diminished 6% in 57 volunteers (P0.001). In 27 others the effects of thigh-length and calf-length boots were compared. In half, pumping with a short boot was undertaken first, and in the remainder, the long boot was applied initially. One-half hour of pumping was followed by 1/2 hour of rest. Immediately afterward the second period of pumping took place and continued for 1/2 hour. A total of four arm vein samples were obtained, one before and after each pumping period. Although, in retrospect, the 1/2-hour rest period was inadequate to permit the subjects to return to basal conditions, statistically significant decreases in euglobin lysis time (P = 0.05) occurred with the long boots. This study shows intermittent calf compression increases fibrinolytic potential locally and this effect can be demonstrated systemically. The greater the volume of tissue compressed, the greater the response. The efficacy of intermittent venous compression in reducing the incidence of deep venous thrombosis may be due, in part, to localized induction of fibrinolysis.
- Published
- 1980
32. Characterization of macrophage chemotaxins in tumor cell cultures and comparison with lymphocyte-derived chemotactic factors
- Author
-
M S, Meltzer, M M, Stevenson, and E J, Leonard
- Subjects
Male ,Chemotaxis, Leukocyte ,Mice ,Mice, Inbred C3H ,Chemotaxis ,Macrophages ,Animals ,Ascitic Fluid ,Lymphocytes ,Sarcoma, Experimental ,Cell Division ,Cells, Cultured ,Culture Media - Abstract
Culture fluids from five murine sarcomas were chemotactic for syngeneic peritoneal macrophages in vitro. Peritoneal macrophages from mice infected with Mycobacterium bovis, strain Bacillus Calmette-Guérin, were more responsive to the chemotactic factor in tumor cultures than were normal macrophages. Peritoneal granulocytes, however, did not significantly respond to this factor. The level of chemotactic activity in tumor cultures paralleled cell growth for all five tumors; maximal levels occurred during log growth. Culture medium alone or fluids from proliferating spleen cell cultures stimulated with mitogens did not have detectable chemotactic activity. Chromatography of the tumor culture fluids resulted in a single peak of chemotactic activity in the 15,000-molecular weight range on Sephadex G-100 and at about 7.5 mmho/cm specific conductance on diethylaminoethyl cellulose. By both biological and physicochemical characteristics, the chemotactic activity in tumor culture fluids was different from mouse lymphocyte-derived chemotactic factor.
- Published
- 1977
33. Activation of macrophages for killing of rickettsiae: analysis of macrophage effector function after rickettsial inoculation of inbred mouse strains
- Author
-
C A, Nacy, M S, Meltzer, E J, Leonard, M M, Stevenson, and E, Skamene
- Subjects
Orientia tsutsugamushi ,Lymphokines ,Mice ,Mice, Inbred BALB C ,Mice, Inbred C3H ,Species Specificity ,Macrophages ,Animals ,Mice, Inbred Strains ,Disease Susceptibility ,Macrophage Activation ,Immunity, Innate - Published
- 1983
34. Mandatory AIDS testing--step in the wrong direction
- Author
-
M M, Stevenson
- Subjects
Acquired Immunodeficiency Syndrome ,Legislation, Medical ,Humans ,West Virginia - Published
- 1987
35. Murine malaria: resistance of AXB/BXA recombinant inbred mice to Plasmodium chabaudi
- Author
-
E Skamene and M M Stevenson
- Subjects
Male ,Immunology ,Mice, Inbred Strains ,Parasitemia ,Microbiology ,law.invention ,Plasmodium chabaudi ,Rodent Diseases ,Mice ,Sex Factors ,Inbred strain ,Genetic linkage ,law ,medicine ,Animals ,Typing ,Crosses, Genetic ,Genetics ,biology ,Strain (biology) ,Recombinant inbred strain ,medicine.disease ,biology.organism_classification ,Immunity, Innate ,Malaria ,Infectious Diseases ,Recombinant DNA ,Parasitology ,Female ,Spleen ,Research Article - Abstract
The level of resistance to infection with Plasmodium chabaudi is genetically controlled. We have previously reported that a single dominant gene is responsible for the variation in host resistance to malaria between susceptible A/J- and resistant C57BL-derived mice. In the present study, recombinant inbred strain analysis was performed with AXB/BXA recombinant inbred strains derived from A/J and C57BL/6 progenitors. Typing of 17 AXB/BXA recombinant inbred strains confirmed the unigenic control of inheritance in this particular strain combination and allowed us to demonstrate genetic linkage between the traits of resistance (defined as a prolonged survival and a low peak parasitemia) and the magnitude of splenomegaly. The influence of sex on the course of infection, which we previously reported in the examination of segregating populations (Stevenson et al., Infect. Immun. 38:80-88, 1982), was again demonstrated in the survey of RI strains.
- Published
- 1985
36. Histological changes in the spleen and liver of C57BL/6 and A/J mice during Plasmodium chabaudi AS infection
- Author
-
M M, Stevenson and G, Kraal
- Subjects
Mice, Inbred C57BL ,Mice ,Time Factors ,Liver ,Mice, Inbred A ,Macrophages ,T-Lymphocytes ,Splenomegaly ,Esterases ,Animals ,Antibodies, Monoclonal ,Spleen ,Malaria - Abstract
The level of resistance to infection in inbred mice with the murine malaria species Plasmodium chabaudi AS is genetically determined. Resistant C57BL/6, which are able to eliminate the parasite by 4 weeks, develop marked splenomegaly and survive the infection. Susceptible A/J mice, which succumb to infection (mean survival time = 10 days), develop only minimal splenomegaly. In order to determine if gross differences in the organization, number, and type of spleen cells are related to the outcome of infection with P. chabaudi AS, the development of splenomegaly was examined by enzyme and immunohistochemical methods during the first week after infection. Cryostat sections of spleens removed from normal animals of both strains and at 4 and 7 days after intraperitoneal infection with 10(6) parasitized erythrocytes were stained for enzyme (acid phosphatase and nonspecific esterase) and immunohistochemistry with conventional monoclonal antibodies against T cells, B cells, and macrophages as well as with novel rat anti-mouse monoclonal antibodies which define discrete subpopulations of macrophages in the mouse spleen. The livers of normal and infected animals of each strain were also examined. The results of this study demonstrate (1) differences between normal, uninfected B6 and A/J mice in the organization and number of one subpopulation of macrophages in the spleen, the marginal metallophilic macrophages, and (2) marked histological changes in the spleen and liver during the course of infection in both resistant C57BL/6 and susceptible A/J mice. These changes include depletion of cells from the marginal zone of the spleen which, in the case of the marginal metallophilic macrophages, appears to be more severe in susceptible A/J mice.
- Published
- 1989
37. Depressed chemotactic responses in vitro of peritoneal macrophages from tumor-bearing mice
- Author
-
M M, Stevenson and M S, Meltzer
- Subjects
Endotoxins ,Male ,Mice ,Mice, Inbred C3H ,Chemotaxis ,Macrophages ,Immunity ,Animals ,Ascitic Fluid ,Complement System Proteins ,Lymphocytes ,Neoplasms, Experimental ,Methylcholanthrene - Abstract
The in vitro chemotactic responses of peritoneal macrophages from mice bearing transplantable syngeneic 3-methylcholanthrene-induced tumors in their footpads were depressed to about 50% of normal levels. This chemotactic defect to both lymphocyte- and complement-derived stimuli was evident before the appearance of palpable tumor (within 1 week of tumor injection) and persisted until the death of the animal by 6-8 weeks. Chemotactic depression was not observed with macrophages from mice treated with tissue culture medium, fetal calf serum, incomplete Freund's adjuvant, or syngeneic spleen cells.
- Published
- 1976
38. Enhancement of resistance to Listeria monocytogenes infection in mice by pyrimidine analogs
- Author
-
L S, Anthony, M M, Stevenson, and E, Skamene
- Subjects
Male ,Cytosine ,Mice ,Interferon Inducers ,Pyrimidines ,Animals ,Female ,Listeriosis ,Immunity, Innate - Abstract
The modulation of murine host resistance to infection with Listeria monocytogenes by the substituted pyrimidine anti-viral compounds, 2-amino-5-bromo-6-methyl-4-pyrimidinol (ABMP), 2-amino-5-bromo-6-phenyl-4-pyrimidinol (ABPP) and 2-amino-5-iodo-6-phenyl-4-pyrimidinol (AIPP) was investigated. BAF1 mice given three daily injections of ABMP, ABPP (as well as of the interferon-inducer poly I:C) demonstrated enhanced anti-listerial resistance, as measured by a 100-fold increase in the median lethal dose of Listeria compared to vehicle-treated control mice. This enhancement was also detectable as a decrease (up to 100-fold) in the number of viable Listeria recoverable from the livers and spleens of mice during the non-immune phase of natural resistance (24-72 h following infection) to this pathogen. In contrast, AIPP did not enhance anti-listerial resistance. Since each of the effective agents have been shown to induce the production of interferon, the role of interferon in the mechanism of natural resistance to Listeria was evaluated. The serum of untreated B10.A mice infected with Listeria was shown to contain high levels of interferon. Treatment of these mice with a potent anti-mouse interferon antibody preparation completely neutralized circulating interferon activity; however, such treatment had no apparent effect on the growth of Listeria. In addition, mice which received injections of both ABMP and anti-interferon demonstrated a level of resistance identical to that seen in mice given ABMP and normal serum. Based on these results, we propose that although interferon is produced in response to listerial infection, interferon is not a critically important mediator in the mechanism of natural resistance to this pathogen. Furthermore, it appears that the immunomodulating activity of these experimental compounds does not involve interferon.
- Published
- 1984
39. Natural resistance to listeriosis: role of host inflammatory responsiveness
- Author
-
M M, Stevenson, F, Gervais, and E, Skamene
- Subjects
Inflammation ,Mice ,Genes, MHC Class II ,Animals ,Complement C5 ,Listeriosis ,Mice, Inbred Strains ,Macrophage Activation ,Immunity, Innate - Abstract
The accumulation of inflammatory macrophages at the infective foci appears to represent the major host defense mechanism during the early or innate phase of resistance to infection with Listeria monocytogenes. Certain inbred strains of mice, such as A/J [A] have genetically-determined defects in macrophage mobilization in vivo in response to intraperitoneal (IP) treatment with the nonspecific inflammatory stimulus, thioglycollate. These strains of mice are also genetically-susceptible to infection with Listeria. In contrast, other strains (C57BL/6J or B10.A/SgSn [B]) are high responders for both genetically-determined traits. Linkage analysis of the two traits in backcross progeny showed that the trait of a high macrophage inflammatory response segregates with the trait of resistance to Listeria. These observations suggested that the gene(s) controlling the level of the macrophage inflammatory response is identical with or linked to the gene(s) controlling resistance to Listeria. We have found additional evidence to support this hypothesis by analyzing the expression of the two traits in 12 AXB/BXA recombinant inbred [RI] mouse strains derived from progenitor B (high macrophage response, Listeria-resistant) and A (low macrophage response, Listeria-susceptible) mice. Furthermore, those AXB/BXA strains, which like progenitor A mice, are susceptible to infection with Listeria exhibit a defect in the number of polymorphonuclear leukocytes recovered from peritoneal exudates 18 h after IP injection with thioglycollate. The strain distribution pattern of both the resistance/susceptibility to Listeria and the leukocyte inflammatory response in RI strains is concordant with that of Hc allele coding for effective/defective levels of C5 complement protein.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1984
40. Studies of platelet aggregation, plasma adenosine diphosphate breakdown and blood coagulation in magnesium deficient calves and rats
- Author
-
M M, Stevenson and I I, Yoder
- Subjects
Blood Platelets ,Platelet Adhesiveness ,Adenine Nucleotides ,Spectrophotometry ,Animals ,Cattle ,Magnesium ,Blood Coagulation Tests ,Magnesium Deficiency ,Blood Cell Count ,Rats - Published
- 1970
41. Gangrene of an extremity in the newborn
- Author
-
E F, Gilbert, G R, Hogan, M M, Stevenson, and H, Suzuki
- Subjects
Femoral Artery ,Gangrene ,Male ,Hematoma ,Leg ,Diseases in Twins ,Infant, Newborn ,Humans ,Infant, Newborn, Diseases - Published
- 1970
42. The incidence of congenital bleeding disorders in West Virginia
- Author
-
M M, Stevenson
- Subjects
Humans ,Blood Coagulation Disorders ,West Virginia ,Hemophilia A ,Hemophilia B - Published
- 1968
43. Rh 'null' is not always null
- Author
-
J Swoyer, A M Tanner, V Anido, and M M Stevenson
- Subjects
Adult ,Isoantigens ,Pathology ,medicine.medical_specialty ,Erythrocytes ,Rh-Hr Blood-Group System ,business.industry ,Null (mathematics) ,General Engineering ,General Medicine ,Middle Aged ,Antibodies, Anti-Idiotypic ,Immunology ,medicine ,Humans ,General Earth and Planetary Sciences ,Female ,Anemia, Hemolytic, Autoimmune ,business ,Research Article ,General Environmental Science - Published
- 1973
44. Surgery in the hemophiliac patient
- Author
-
B Zimmermann, M M Stevenson, Jerome R. Klingbeil, and T J Tarnay
- Subjects
medicine.medical_specialty ,business.industry ,Medicine ,Surgery ,business - Published
- 1967
45. 'Transmission Tracker - Dirofilaria'- a public dashboard to assess in real-time the temperature-bounded transmissibility of canine heartworm across Australia.
- Author
-
Atkinson PJ, Stevenson M, O'Handley R, Nielsen T, and Caraguel C
- Abstract
The causative agent of canine heartworm disease, Dirofilaria immitis, requires specific temperature conditions to mature within its mosquito vector, and therefore (re-)infect a canid host. Suitable temperature conditions are not continuously met for locations where most (>97%) Australians and their pet dogs live. The length of the disruption in the transmissibility of D. immitis varies greatly across Australia, and to some degree, between years. We developed an online dashboard 'Transmission Tracker - Dirofilaria' that processes near real-time temperature records across Australia and allows users to enquire about historical and current weather suitability for canine heartworm transmission at any Australian postcode of their interest. This information allows veterinarians to access when, and for how long, heartworm may be transmitted at a specific location, assess the associated risk of infection and advise on a patient-dependent dirofilariosis prevention plan for their canine patients and guardians. Our dashboard is publicly accessible at: https://heartworm-mapping.adelaide.edu.au/shiny/., (© 2024 The Author(s). Australian Veterinary Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Veterinary Association.)
- Published
- 2024
- Full Text
- View/download PDF
46. A machine-learning assisted review of the use of habit formation in medication adherence interventions for long-term conditions.
- Author
-
Robinson L, Arden MA, Dawson S, Walters SJ, Wildman MJ, and Stevenson M
- Subjects
- Humans, Health Behavior, Medication Adherence, Machine Learning, Habits
- Abstract
Adherence to medication in long-term conditions is around 50%. The key components of successful interventions to improve medication adherence remain unclear, particularly when examined over prolonged follow-up periods. Behaviour change theories are increasingly interested in the utility of habit formation for the maintenance of health behaviour change, but there is no documentation on how habit has been conceptualised in the medication adherence intervention literature, or what effect the key technique identified in habit formation theory (context dependent repetition) has in these studies. To examine this, a machine-learning assisted review was conducted. Searches of MEDLINE, EMBASE and PSYCInfo and the reference list of a comprehensive systematic review of medication adherence interventions yielded 5973 articles. Machine learning-assisted title and abstract screening identified 15 independent RCTs published between 1976 and 2021, including 18 intervention comparisons of interest. Key findings indicate that conceptualisations of habit in the medication adherence literature are varied and behaviour change technique coding identified only six studies which explicitly described using habit formation. Future work should aim to develop this evidence base, drawing on contemporary habit theory and with explicit demonstration of what techniques have been used to promote habit formation.
- Published
- 2024
- Full Text
- View/download PDF
47. Descriptive epidemiology of smothering in Australian commercial free-range layer hen farms.
- Author
-
Chowdhury P, Hemsworth PH, Fisher AD, Rice M, Galea RY, Taylor PS, and Stevenson M
- Subjects
- Humans, Animals, Female, Prospective Studies, Farms, Animal Husbandry, Asphyxia epidemiology, Asphyxia veterinary, Australia epidemiology, Poultry, Chickens, Poultry Diseases epidemiology
- Abstract
Since the early 2000 s the practice of free-range egg production has increased in developed countries, partly driven by consumer perception that free-range housing is better for hen welfare. While poultry in free-range systems have more behavioural opportunities compared with poultry in caged systems, free-range systems are associated with greater frequencies of infectious disease, predation and 'smothering', a condition where birds pile on top of one another with death occurring due to suffocation. Although the frequency of smothering deaths in Australian free-range layer poultry is anecdotally high, there is a lack of empirical evidence quantifying smothering cause-specific mortality rates and identifying factors that place birds at higher risk of death from smothering. This was a prospective cohort study of poultry flocks managed by three commercial free-range layer organisations in Eastern Australia. Flocks were enrolled into the study from 1 January 2019 to 29 March 2021 and were followed until the end of lay or until the end of the study on 31 March 2022, whichever occurred first. Throughout the follow-up period flock managers provided production details for each flock and details of smothering events using custom-designed logbooks.A total of 84 flocks were enrolled in the study: 32 from Organisation 1, 35 from Organisation 2 and 17 from Organisation 3. The number of birds per flock ranged from 16,000 to 45,000. The total mortality rate was 1131 deaths per 10,000 bird-years. Smothering mortality rate across the three organisations was 183 (minimum 133, maximum 223) deaths per 10,000 bird-years at risk. Smothering accounted for around 16% (minimum 9%, maximum 22%) of all deaths.We identified no distinctive temporal pattern in daily smothering risk as a function of either the number of days since placement or calendar date. The locations of smothering events in sheds and in the outdoor range were not consistent, with relatively large numbers of smothering events occurring in specific locations for some sheds but not others. To the best of our knowledge, this study is the largest prospective study of smothering mortality in commercial free-range layer flocks conducted to date. Estimates of smothering incidence rate and how that varies within and between flocks and organisations over time provides a critically important benchmark for further investigations into this substantial area of productivity loss., Competing Interests: Declaration of Competing Interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
48. Health surveillance representative of koala (Phascolarctos cinereus) distribution in Victoria, Australia.
- Author
-
Cooley M, Whiteley P, Thornton G, and Stevenson M
- Subjects
- Animals, Victoria epidemiology, Retrospective Studies, Ecosystem, Phascolarctidae
- Abstract
Health surveillance of wildlife populations is essential for conservation and reduction of the impacts of disease. Population declines and areas of overabundance of koalas (Phascolarctos cinereus) can disrupt the overall survival of the species as well as its habitat. This retrospective study was conducted to describe population distributions, identify areas which need increased surveillance and improve koala health surveillance methodology by Wildlife Health Victoria: Surveillance (WHV:S) at the Veterinary School of The University of Melbourne. Twelve years of Victorian koala observation data from the Atlas of Living Australia combined with surveillance data from WHV:S were used to create choropleth maps, using Quantum Geographic Information Systems of populations and surveillance events, visually representing hot spots. This data was further used to calculate health surveillance efforts between 2008 to the beginning of 2020. Analysis ranked postcodes throughout Victoria from low surveillance efforts to high, using standardised surveillance ratio's 95% confidence interval upper limits which were mapped using a colour gradient. This identified postcodes which need increased surveillance effort, corresponding to areas with high koala observations and low surveillance submissions. This analysis can guide surveillance for postcodes with koalas that were under-represented and inform improved methodology of future surveillance by WHV:S. The specific advice for improvements to WHV:S includes utilisation of citizen science and syndromic surveillance, website improvement, increasing community awareness and more. The limitations of this study were discussed., (© 2022 The Authors. Australian Veterinary Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Veterinary Association.)
- Published
- 2022
- Full Text
- View/download PDF
49. Persistent HIV-1 transcription in CD4 + T cells from ART-suppressed individuals can originate from biologically competent proviruses.
- Author
-
Vignoles M, Andrade V, Noguera M, Brander C, Mavian C, Salemi M, Paredes R, Sharkey M, and Stevenson M
- Abstract
HIV-1 is able to persist in the face of potent antiretroviral therapy (ART). A number of strategies are being explored to allow ART-free viral remission or viral eradication. In order to gauge the progress of these strategies, assays with which to measure viral reservoir size and activity are needed. In a large percentage of aviremic individuals on suppressive ART, viral transcripts can be detected in peripheral blood CD4
+ T cells. While this cell-associated RNA has been considered as a marker of viral reservoir activity, it is unclear whether cell-associated viral transcripts in aviremic individuals originate from biologically competent proviruses as opposed to being a product of abortive transcription from defective proviruses. We assessed whether cell-associated viral RNA in peripheral blood CD4+ T cells from aviremic individuals on ART originated from biologically competent proviruses. We demonstrate that cell-associated viral RNA transcripts were highly related to viral sequences obtained by ex vivo outgrowth. This relationship was also observed when viral transcription in the outgrowth cultures was limited to donor CD4+ T cells. Our study indicates that cell-associated viral RNA warrants further consideration as a viral reservoir surrogate in individuals on suppressive ART., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)- Published
- 2021
- Full Text
- View/download PDF
50. Hypoxia stimulates angiogenesis and a metabolic switch in human parathyroid adenoma cells.
- Author
-
Lines KE, Stevenson M, Mihai R, Grigorieva IV, Shariq OA, Gaynor KU, Jeyabalan J, Javid M, and Thakker RV
- Abstract
Hypoxia, a primary stimulus for angiogenesis, is important for tumour proliferation and survival. The effects of hypoxia on parathyroid tumour cells, which may also be important for parathyroid autotransplantation in patients, are, however, unknown. We, therefore, assessed the effects of hypoxia on gene expression in parathyroid adenoma (PA) cells from patients with primary hyperparathyroidism. Cell suspensions from human PAs were cultured under normoxic or hypoxic conditions and then subjected to cDNA expression analysis. In total, 549 genes were significantly upregulated and 873 significantly downregulated. The most highly upregulated genes (carbonic anhydrase 9 ( CA9 ), Solute carrier family 2A1 ( SLC2A1 ) and hypoxia-inducible lipid droplet-associated protein ( HIG2 )) had known involvement in hypoxia responses. Dysregulation of oxidative phosphorylation and glycolysis pathway genes were also observed, consistent with data indicating that cells shift metabolic strategy of ATP production in hypoxic conditions and that tumour cells predominantly utilise anaerobic glycolysis for energy production. Proliferation- and angiogenesis-associated genes linked with growth factor signalling, such as mitogen-activated protein kinase kinase 1 ( MAP2K1 ), Jun proto-oncogene ( JUN ) and ETS proto-oncogene 1 ( ETS1 ), were increased, however, Ras association domain family member 1 ( RASSF1 ), an inhibitor of proliferation was also upregulated, indicating these pathways are unlikely to be biased towards proliferation. Overall, there appeared to be a shift in growth factor signalling pathways from Jak-Stat and Ras signaling to extracellular signal-regulated kinases (ERKs) and hypoxia-inducible factor (HIF)-1α signalling. Thus, our data demonstrate that PAs, under hypoxic conditions, promote the expression of genes known to stimulate angiogenesis, as well as undergoing a metabolic switch., Competing Interests: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (© The author.)
- Published
- 2021
- Full Text
- View/download PDF
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