A5019802377- Immune Cell Function and Interaction
- Aortic aneurysm repair treatments
- Diabetes and associated disorders
- Pancreatic function and diabetes
- Bacillus and Francisella bacterial research
- Aortic Disease and Treatment Approaches
- Yersinia bacterium, plague, ectoparasites research
- Immune cells in cancer
- Macrophage Migration Inhibitory Factor
- T-cell and B-cell Immunology
- Cardiovascular Disease and Adiposity
- Poxvirus research and outbreaks
- Infectious Aortic and Vascular Conditions
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Cardiovascular Health and Disease Prevention
- Mangiferin and Mango Extracts
- Renin-Angiotensin System Studies
- Adipose Tissue and Metabolism
- Nitric Oxide and Endothelin Effects
- Hormonal Regulation and Hypertension
- Heart Failure Treatment and Management
- Microbial Inactivation Methods
- Inflammation biomarkers and pathways
- Biomarkers in Disease Mechanisms
University of Missouri
2018-2025
National Institute of Infectious Diseases
2012-2020
University of Kansas Medical Center
2017-2020
Gifu University
2012-2016
University of Kansas
2016
University of Liverpool
2015
Abstract Aging of the vasculature is characterized by endothelial dysfunction and arterial stiffening, two key events in pathogenesis cardiovascular disease (CVD). Treatment with sodium glucose transporter 2 (SGLT2) inhibitors now known to decrease morbidity mortality type diabetes. However, whether SGLT2 inhibition attenuates vascular aging unknown. We first confirmed a cohort adult subjects that associated impaired function increased stiffness these variables are inversely correlated....
Abstract Studies support a role for natural killer (NK) cells in cancer control, making these attractive immunotherapy. One method being tested to make effective NK is the ex vivo activation with interleukin (IL)-12, IL-15, and IL-18. We demonstrate that this induces NKG2D ligands on cells. By engaging NKG2D, ligand expression eliminated ability of both mouse human control tumor growth vitro, respectively. NKG2D-NKG2D interaction between reduced cell proliferation, CD25 T-bet expression,...
Objective— Abdominal aortic aneurysm is caused by the accumulation of inflammatory cells in wall. Our recent studies demonstrated that inhibition Notch signaling attenuates abdominal formation shifting macrophage balance towards anti-inflammatory (M2) phenotype. Using IL12p40 −/− (interleukin 12 p40) mice, we investigated effects M2-predominant macrophages on development aneurysm. Approach and Results— Male (8–10 week-old) wild-type mice (n=15) C57BL/6 background were infused with Ang II...
A novel competitive enzyme-linked immunosorbent assay (cELISA) was developed and evaluated for detection of antibodies against Francisella tularensis in humans. The is based on the ability serum to inhibit binding monoclonal (MAbs) directed F. lipopolysaccharide antigens. using samples tularemia patients, inactivated tularensis-immunized rabbits, tularensis-infected mice. Antibodies were successfully detected patients as well immunized infected animals. cELISA method compared indirect ELISA...
Arterial stiffening, a characteristic feature of obesity and type 2 diabetes (T2D), contributes to the development progression cardiovascular diseases. Herein we establish that adropin is decreased in obese T2D models furthermore provide evidence reduced may directly contribute arterial stiffening. Collectively, findings from this work support notion “hypoadropinemia” should be considered as putative target for prevention treatment stiffening T2D.
Obstructive sleep apnea (OSA), characterized by episodes of intermittent hypoxia (IH), is highly prevalent in patients with abdominal aortic aneurysm (AAA). However, whether IH serves as an independent risk factor for AAA development remains to be investigated. Here, we determined the effects chronic (6 mo) on angiotensin (Ang II)-induced C57BL/6J male mice and investigated underlying mechanisms cultured vascular smooth muscle cells (SMCs). increased susceptibility develop response Ang II...
Abstract Abdominal aortic aneurysm (AAA) is characterized by transmural infiltration of myeloid cells at the vascular injury site. Previously, we reported preventive effects Notch deficiency on development AAA reduction infiltrating cells. In this study, examined if inhibition attenuates progression pre-established and potential implications. Pharmacological inhibitor (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-(S)-phenylglycine t-butyl ester; DAPT) was administered subcutaneously three times a...
Naïve macrophages (Mφ) polarize in response to various environmental cues a spectrum of cells that have distinct biological functions. The extreme ends the are classified as M1 and M2 macrophages. Previously, we demonstrated Notch1 deficiency promotes Tgf-β2 dependent M2-polarization mouse model abdominal aortic aneurysm. present studies aimed characterize unique set genes regulated by signaling macrophage polarization. Bone marrow derived isolated from WT or
Francisella tularensis subspecies tularensis, the etiological agent of tularemia, is highly pathogenic to humans and animals. However, SCHU strain F. P0 maintained by passaging in artificial media has been found be attenuated. To better understand molecular mechanisms behind pathogenicity SCHU, we attempted isolate virulent bacteria serial passages mice. P5 obtained after 5th mice remained avirulent, while P9 9th was completely Moreover, grew more efficiently J774.1 murine macrophages...
Vascular insulin resistance, a major characteristic of obesity and type 2 diabetes (T2D), manifests with blunting insulin-induced vasodilation. Although there is evidence that females are more whole body sensitive than males in the healthy state, whether sex differences exist vascular sensitivity unclear. Also uncertain weight loss can reestablish T2D. The purpose this investigation was to 1) establish if vasodilatory responses absence disease, 2) determine female affords protection against...
Background Development of abdominal aortic aneurysm (AAA) is associated with proinflammatory cytokines including interleukin‐12 (IL12). Deficiency interleukin 12p40 (IL12p40) increases localized fibrotic events by promoting TGFβ2 (transforming growth factor β)‐dependent anti‐inflammatory response. Here, we determined whether IL12p40 deficiency in apolipoprotein E ‐/‐ mice attenuates the development AAA antagonizing Methods and Results Double knockout (DKO) were generated crossbreeding...
Impaired endothelial insulin signaling and consequent blunting of insulin-induced vasodilation is a feature type 2 diabetes (T2D) that contributes to vascular disease glycemic dysregulation. However, the molecular mechanisms underlying resistance remain poorly known. Herein, we tested hypothesis in T2D attributed reduced expression heat shock protein 72 (HSP72). HSP72 cytoprotective chaperone can be upregulated with heating reported promote sensitivity metabolically active tissues, part via...
Abstract Clinical and experimental studies show that angiotensin II (AngII) promotes vascular pathology via activation of AngII type 1 receptors (AT1Rs). We recently reported NP‐6A4, a selective peptide agonist for 2 receptor (AT2R), exerts protective effects on human cells subjected to serum starvation or doxorubicin exposure. In this study, we investigated whether NP‐6A4–induced AT2R could mitigate AngII‐induced abdominal aortic aneurism (AAA) using AngII‐treated Apoe −/− mice. Male mice...
Abstract NK group 2 member D (NKG2D) is a strong cell–activating receptor, with engagement by ligands triggering granule release and cytokine production. The function of NKG2D signaling in cells has largely been studied the context receptor expressed on surface target cells. We report that upon activation IL-12, IL-15, IL-18 human express UL16 binding protein family cell surface. NKG2D-ligand interaction between cytokine-stimulated increases activity metalloprotease TNF-α–converting enzyme....
Tularemia, a highly infectious zoonotic disease caused by Francisella tularensis, occurs sporadically in Japan. However, little is known about the prevalence of wild animals. A total 632 samples obtained from 150 Japanese black bears, 142 hares, 120 small rodents, 97 rats, 53 raptors, 26 monkeys, 21 raccoon dogs, 20 masked palm civets, and three red foxes between 2002 2010 were investigated for presence antibodies to F. tularensis competitive enzyme-linked immunosorbent assay (cELISA)...
The antibiotic susceptibilities of 36 isolates Japanese Francisella tularensis, an etiological agent the zoonotic disease tularemia, were analyzed using E test. All susceptible to ciprofloxacin, doxycycline, erythromycin, and gentamicin but resistant benzylpenicillin cephalothin. susceptibility seven other β-lactams (aztreonam, cefotaxime, cefoxitin, ceftriaxone, cefuroxime, imipenem, meropenem) varied among isolates. These findings suggest that guidelines for treatment tularemia issued by...
Abstract Abdominal aortic aneurysm (AAA) is a localized pathological dilation of the aorta exceeding normal diameter (∼20 mm) by more than 50% its original size (≥30 mm), accounting for approximately 150000–200000 deaths worldwide per year. We previously reported that Notch inhibition does not decrease pre-established AAA at late stage disease. Here, we examined whether potent pharmacologic inhibitor signaling (DAPT (N-[N-(3,5-Difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester)),...
An abdominal aortic aneurysm (AAA) is defined as a localized dilation of the aorta that exceeds maximal intraluminal diameter (MILD) by 1.5 times its original size. Clinical and experimental studies have shown small aneurysms may rupture, while subpopulation large remain stable. Thus, in addition to measurement aorta, knowledge structural traits vessel wall provide important information assess stability AAA. Aortic stiffening has recently emerged reliable tool determine early changes...
Key Points The NKG2D ligand ULBP-4 is expressed on healthy monocytes. Monocyte expression regulates by NK cells.
Abstract The NK group 2 member D (NKG2D) immune receptor is implicated in both human and mouse autoimmune diabetes. However, the significance of NKG2D diabetes pathogenesis has been unclear due to conflicting reports as importance this NOD model. In study we demonstrate that expression affects development by at least two previously undescribed, opposing, mechanisms. First, ligand H60a induced on activated T cells, NKG2D–H60a interaction during CD8+ cell differentiation into CTLs generally...
Pullulanase, an enzyme that catalyzes the hydrolysis of polysaccharides, has been identified in a broad range organisms, including bacteria, yeasts, fungi, and animals. The pullulanase (pulB; FTT_0412c) F. tularensis subspecies Schu S4 is considered to be homologue type I (pulA) other Francisella subspecies. significance obscure until now. In present study, we characterized recombinant PulB SCHU P9, which was expressed as his-tagged protein Escherichia coli. confirmed by its enzymatic...
Samples taken from 428 wild animals and 126 ticks, collected a tularemia-endemic area in Japan between 2005 2013, were analyzed for the presence of Francisella tularensis. F. tularensis was isolated Japanese hare carcass whereas samples live ticks negative by real-time PCR. Our results suggest that is still present although its prevalence considerably low even areas where tularemia endemic.