Browsing by Subject "immunology"

Now showing 1 - 6 of 6

Open Access
Development and Evaluation of a Novel Mouse Model of Asphyxial Cardiac Arrest Revealed Severely Impaired Lymphopoiesis After Resuscitation.
(J Am Heart Assoc, 2021-05-20) Wang, Wei; Li, Ran; Miao, Wanying; Evans, Cody; Lu, Liping; Lyu, Jingjun; Li, Xuan; Warner, David S; Zhong, Xiaoping; Hoffmann, Ulrike; Sheng, Huaxin; Yang, Wei
Background Animal disease models represent the cornerstone in basic cardiac arrest (CA) research. However, current experimental models of CA and resuscitation in mice are limited. In this study, we aimed to develop a mouse model of asphyxial CA followed by cardiopulmonary resuscitation (CPR), and to characterize the immune response after asphyxial CA/CPR. Methods and Results CA was induced in mice by switching from an O2/N2 mixture to 100% N2 gas for mechanical ventilation under anesthesia. Real-time measurements of blood pressure, brain tissue oxygen, cerebral blood flow, and ECG confirmed asphyxia and ensuing CA. After a defined CA period, mice were resuscitated with intravenous epinephrine administration and chest compression. We subjected young adult and aged mice to this model, and found that after CA/CPR, mice from both groups exhibited significant neurologic deficits compared with sham mice. Analysis of post-CA brain confirmed neuroinflammation. Detailed characterization of the post-CA immune response in the peripheral organs of both young adult and aged mice revealed that at the subacute phase following asphyxial CA/CPR, the immune system was markedly suppressed as manifested by drastic atrophy of the spleen and thymus, and profound lymphopenia. Finally, our data showed that post-CA systemic lymphopenia was accompanied with impaired T and B lymphopoiesis in the thymus and bone marrow, respectively. Conclusions In this study, we established a novel validated asphyxial CA model in mice. Using this new model, we further demonstrated that asphyxial CA/CPR markedly affects both the nervous and immune systems, and notably impairs lymphopoiesis of T and B cells.
Open Access
Frequency of Occult High-Grade Squamous Intraepithelial Neoplasia and Invasive Cancer within Anal Condylomata in Men Who Have Sex with Men
(2010) Schlecht, Hans P; Fugelso, Dana K; Murphy, Ryan K; Wagner, Katiri T; Doweiko, John P; Proper, JoAnn; Dezube, Bruce J; Panther, Lori A
Human papillomavirus causes anal condylomata, high-grade anal intraepithelial neoplasia, and anal squamous cell cancer. We found high-grade intraepithelial neoplasia or squamous cell cancer in 75 (47%) of 159 HIV-seropositive men who have sex with men (MSM) and in 42 (26%) of 160 HIV-seronegative MSM with anal condylomata meriting surgery (P < .001, determined by use of the X-2 test). Anal condylomata in MSM often harbor high-grade intraepithelial neoplasia and squamous cell cancer.
Open Access
Global Trends in Typhoid and Paratyphoid Fever
(2010) Crump, John A; Mintz, Eric D
Typhoid and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and Southeast Asia, where enteric fever is associated with poor sanitation and unsafe food and water. High-quality incidence data from Asia are underpinning efforts to expand access to typhoid vaccines. Efforts are underway to develop vaccines that are immunogenic in infants after a single dose and that can be produced locally in countries of endemicity. The growing importance of Salmonella enterica serotype Paratyphi A in Asia is concerning. Antimicrobial resistance has sequentially emerged to traditional first-line drugs, fluoroquinolones, and third-generation cephalosporins, posing patient treatment challenges. Azithromycin has proven to be an effective alternative for treatment of uncomplicated typhoid fever. The availability of full genome sequences for S. enterica serotype Typhi and S. enterica serotype Paratyphi A confirms their place as monomorphic, human-adapted pathogens vulnerable to control measures if international efforts can be redoubled.
Open Access
Immunologic Effects of the Renin-Angiotensin System.
(J Am Soc Nephrol, 2017-02-01) Crowley, Steven D; Rudemiller, Nathan P
Inappropriate activation of the renin-angiotensin system (RAS) exacerbates renal and vascular injury. Accordingly, treatment with global RAS antagonists attenuates cardiovascular risk and slows the progression of proteinuric kidney disease. By reducing BP, RAS inhibitors limit secondary immune activation responding to hemodynamic injury in the target organ. However, RAS activation in hematopoietic cells has immunologic effects that diverge from those of RAS stimulation in the kidney and vasculature. In preclinical studies, activating type 1 angiotensin (AT1) receptors in T lymphocytes and myeloid cells blunts the polarization of these cells toward proinflammatory phenotypes, protecting the kidney from hypertensive injury and fibrosis. These endogenous functions of immune AT1 receptors temper the pathogenic actions of renal and vascular AT1 receptors during hypertension. By counteracting the effects of AT1 receptor stimulation in the target organ, exogenous administration of AT2 receptor agonists or angiotensin 1-7 analogs may similarly limit inflammatory injury to the heart and kidney. Moreover, although angiotensin II is the classic effector molecule of the RAS, several RAS enzymes affect immune homeostasis independently of canonic angiotensin II generation. Thus, as reviewed here, multiple components of the RAS signaling cascade influence inflammatory cell phenotype and function with unpredictable and context-specific effects on innate and adaptive immunity.
Open Access
Lessons Learned from the Anaerobe Survey: Historical Perspective and Review of the Most Recent Data (2005-2007)
(2010) Snydman, David R; Jacobus, Nilda V; McDermott, Laura A; Golan, Yoav; Hecht, David W; Goldstein, Ellie JC; Harrell, Lizzie; Jenkins, Stephen; Newton, Duane; Pierson, Carl; Rihs, John D; Yu, Victor L; Venezia, Richard; Finegold, Sydney M; Rosenblatt, Jon E; Gorbach, Sherwood L
Background. The rationale and lessons learned through the evolution of the National Survey for the Susceptibility of Bacteroides fragilis Group from its initiation in 1981 through 2007 are reviewed here. The survey was conceived in 1980 to track emerging antimicrobial resistance in Bacteroides species. Methods. Data from the last 11 years of the survey (1997-2007), including 6574 isolates from 13 medical centers, were analyzed for in vitro antimicrobial resistance to both frequently used and newly developed anti-anaerobic agents. The minimum inhibitory concentrations of the antibiotics were determined using agar dilution in accordance with Clinical and Laboratory Standards Institute recommendations. Results. The analyses revealed that the carbapenems (imipenem, meropenem, ertapenem, and doripenem) and piperacillin-tazobactam were the most active agents against these pathogens, with resistance rates of 0.9%-2.3%. In the most recent 3 years of the survey (2005-2007), resistance to some agents was shown to depend on the species, such as ampicillin-sulbactam against Bacteroides distasonis (20.6%) and tigecycline against Bacteroides uniformis and Bacteroides eggerthii (similar to 7%). Very high resistance rates (>50%) were noted for moxifloxacin and trovafloxacin, particularly against Bacteroides vulgatus. During that period of study, non-B. fragilis Bacteroides species had >40% resistance to clindamycin. Metronidazole-resistant Bacteroides strains were also first reported during that period. Conclusions. In summary, resistance to antibiotics was greater among non-B. fragilis Bacteroides species than among B. fragilis and was especially greater among species with a low frequency of isolation, such as Bacteroides caccae and B. uniformis. The emergence of resistance among the non-B. fragilis Bacteroides species underscores the need for speciation of B. fragilis group isolates and for clinicians to be aware of associations between species and drug resistance.
Open Access
Synergistic Pandemics: Confronting the Global HIV and Tuberculosis Epidemics
(2010) Mayer, Kenneth H; Dukes Hamilton, Carol