Group B Streptococcal Serine-Rich Repeat Proteins Promote Interaction With Fibrinogen and Vaginal Colonization

Wang, Nai-Yu,Patras, Kathryn A.,Seo, Ho Seong,Cavaco, Courtney K.,Rö,sler, Berenice,Neely, Melody N.,Sullam, Paul M.,Doran, Kelly S. Oxford University Press 2014 The Journal of Infectious Diseases Vol.210 No.6

<P>Group B streptococcus (GBS) can cause severe disease in susceptible hosts, including newborns, pregnant women, and the elderly. GBS serine-rich repeat (Srr) surface glycoproteins are important adhesins/invasins in multiple host tissues, including the vagina. However, exact molecular mechanisms contributing to their importance in colonization are unknown. We have recently determined that Srr proteins contain a fibrinogen-binding region (BR) and hypothesize that Srr-mediated fibrinogen binding may contribute to GBS cervicovaginal colonization. In this study, we observed that fibrinogen enhanced wild-type GBS attachment to cervical and vaginal epithelium, and that this was dependent on Srr1. Moreover, purified Srr1-BR peptide bound directly to host cells, and peptide administration in vivo reduced GBS recovery from the vaginal tract. Furthermore, a GBS mutant strain lacking only the Srr1 “latching” domain exhibited decreased adherence in vitro and decreased persistence in a mouse model of GBS vaginal colonization, suggesting the importance of Srr–fibrinogen interactions in the female reproductive tract.</P>

Antioxidant Capacity of Food Mixtures Is Not Correlated with Their Antiproliferative Activity Against MCF-7 Breast Cancer Cells

Sunan Wang,Fan Zhu,Kelly A. Meckling,Massimo F. Marcone 한국식품영양과학회 2013 Journal of medicinal food Vol.16 No.12

Combining different foods may produce additive, synergistic, or antagonistic interactions that may modify certain physiological effects (i.e., anticancer properties). For investigating these interactions and potential synergetic combinations, thirteen foods from three categories, including fruits (raspberries, blackberries, apples, grapes), vegetables (broccoli, tomatoes, mushrooms, purple cauliflowers, onions), and legumes (soy beans, adzuki beans, red kidney beans, black beans), were evaluated for their inhibitory activity against MCF-7 breast cancer cells. Grape, onion, and adzuki bean showed maximal growth inhibition of MCF-7 from the fruit, vegetable, and legume groups, respectively. When these three foods were combined in pairs, unique interactions were observed that were not seen when individual extracts were used. Combining onion and grape resulted in a synergistic antiproliferative effect (APE) against MCF-7 compared with either onion or grape treatment alone. In contrast, combining grape and adzuki bean resulted in an antagonistic interaction. Additionally, four antioxidant assays (total phenolic contents, ferric reducing antioxidant power, 2,2-diphenyl-1-picrylhydrazyl, and oxygen radical absorbance capacity) were further used to evaluate the antioxidant capacities (AC) of individual foods and their combinations. Combining raspberry and adzuki bean extracts demonstrated synergistic AC in all four assays, but they did not show synergistic APE against the MCF-7 cells. Combining broccoli and soy produced antioxidant antagonism, but did not have an antagonistic APE against MCF-7. The synergistic or antagonistic AC of food mixtures did not correlate with the synergistic or antagonistic APE against MCF-7. Further investigation is to determine the mechanisms of these interactions and to predict and enhance the therapeutic benefits of foods and food components through strategic food combinations.

Pathogenesis of Hantaan Virus Infection in Suckling Mice Clinical , Virologic and Serologic Observations

Lee, Ho Wang,Kim, Gum Ryong,Kelly T . Mckee 대한미생물학회 1985 大韓微生物學會誌 Vol.20 No.1

Hemorrhagic fever with renal syndrome (H FRS) is a debilitating disease of humans cau- sed by Hantaan virus (HVI, the prototype member of a newly proposed genus of Bunyaz:Iridae. Studies of HV pathogenesis have been limited by the absence of a well defined model for a virus-induced disease state. In an at- tempt to devise a model for HV pathogenesis in laboratory rodents, newborn outbred suckling ICR mice were shown to be uniformly susceptible to lethal infection with nonmouse adapted HV by intracerebral (IC), intraperitoneal (IP), intramuscular (IM), and subcutaneous (SC) inoculation routes. Clinical coures, mean time to death, and fatal outcome were age-dependent. With an inoculum of 10 LD, mortality was 100% in mice infected within 72h of birth, but declined to 50% by 7 days. By 2-2.5 weeks, animals developed complete resistance to clinical disease. Virus was consistently deteeted in serum by day 6 post-in- fection in IC:- and IP- inoculated animals, and reached peak levels of 10' PFU/ml byday 8; Mice infected IM and SC showed delays in onset of viremia, but achieved similar titers. Immunofluorescent antibody appeared by 17-18 days, and neutralizing antibody by 15 days, in all experimental groups. Two of 8 inbred mouse strains were identified as resistant to clinical disease: SJL/J and A/J. Manipulation of this model will allow investigation of natural rodent pathogenesis with HV, as well as offer insight into disease mechanisms and therapy of HFRS.

Endoscopic Suturing for the Prevention and Treatment of Complications Associated with Endoscopic Mucosal Resection of Large Duodenal Adenomas

Jaeil Chung,Kelly Wang,Alexander Podboy,Srinivas Gaddam,Simon K. Lo 대한소화기내시경학회 2022 Clinical Endoscopy Vol.55 No.1

Background/Aims: Endoscopic mucosal resection (EMR) is the primary treatment for duodenal adenomas; however, it is associatedwith a high risk of perforation and bleeding, especially with larger lesions. The goal of this study was to demonstrate the feasibilityand safety of endoscopic suturing (ES) for the closure of mucosal defects after duodenal EMR. Methods: Consecutive adult patients who underwent ES of large mucosal defects after EMR of large (>2 cm) duodenal adenomaswere retrospectively enrolled. The OverStitch ES system was employed for closing mucosal defects after EMR. Clinical outcomes andcomplications, including delayed bleeding and perforation, were documented. Results: During the study period, ES of mucosal defects was performed in seven patients in eight sessions (six for prophylaxisand two for the treatment of perforation). All ES sessions were technically successful. No early or delayed post-EMR bleeding wasrecorded. In addition, no clinically obvious duodenal stricture or recurrence was encountered on endoscopic follow-up evaluation,and no patients required subsequent surgical intervention. Conclusions: ES for the prevention and treatment of duodenal perforation after EMR is technically feasible, safe, and effective. ES should be considered an option for preventing or treating perforations associated with EMR of large duodenal adenomas.

Association of two independent functional risk haplotypes in <i>TNIP1</i> with systemic lupus erythematosus

Adrianto, Indra,Wang, Shaofeng,Wiley, Graham B.,Lessard, Christopher J.,Kelly, Jennifer A.,Adler, Adam J.,Glenn, Stuart B.,Williams, Adrienne H.,Ziegler, Julie T.,Comeau, Mary E.,Marion, Miranda C.,Wa Wiley Subscription Services, Inc., A Wiley Company 2012 Vol.64 No.11

<P><B>Abstract</B></P><P><B>Objective</B></P><P>Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and altered type I interferon expression. Genetic surveys and genome‐wide association studies have identified >30 SLE susceptibility genes. One of these genes, <I>TNIP1</I>, encodes the ABIN1 protein. ABIN1 functions in the immune system by restricting NF‐κB signaling. The present study was undertaken to investigate the genetic factors that influence association with SLE in genes that regulate the NF‐κB pathway.</P><P><B>Methods</B></P><P>We analyzed a dense set of genetic markers spanning <I>TNIP1</I> and <I>TAX1BP1</I>, as well as the <I>TNIP1</I> homolog <I>TNIP2</I>, in case–control populations of diverse ethnic origins. <I>TNIP1</I>, <I>TNIP2</I>, and <I>TAX1BP1</I> were fine‐mapped in a total of 8,372 SLE cases and 7,492 healthy controls from European‐ancestry, African American, Hispanic, East Asian, and African American Gullah populations. Levels of <I>TNIP1</I> messenger RNA (mRNA) and ABIN1 protein in Epstein‐Barr virus–transformed human B cell lines were analyzed by quantitative reverse transcription–polymerase chain reaction and Western blotting, respectively.</P><P><B>Results</B></P><P>We found significant associations between SLE and genetic variants within <I>TNIP1</I>, but not in <I>TNIP2</I> or <I>TAX1BP1</I>. After resequencing and imputation, we identified 2 independent risk haplotypes within <I>TNIP1</I> in individuals of European ancestry that were also present in African American and Hispanic populations. Levels of <I>TNIP1</I> mRNA and ABIN1 protein were reduced among subjects with these haplotypes, suggesting that they harbor hypomorphic functional variants that influence susceptibility to SLE by restricting ABIN1 expression.</P><P><B>Conclusion</B></P><P>Our results confirm the association signals between SLE and <I>TNIP1</I> variants in multiple populations and provide new insight into the mechanism by which <I>TNIP1</I> variants may contribute to SLE pathogenesis.</P>

Alkaloids of Linderae Radix suppressed the lipopolysaccharide-induced expression of cytokines in cultured macrophage RAW 264.7 cells

David Jiyao Chou,Kelly Yinching Lam,Jianping Chen,Ping Yao,Tina Tingxia Dong,Aizhen Xiong,Guixin Chou,Zhengtao Wang,Karl Wah-Keung Tsim 셀메드 세포교정의약학회 2014 셀메드 (CellMed) Vol.4 No.4

Linderae Radix, the dry roots of Lindera aggregata (Sims) Kosterm, has long been used as traditional Chinese medicine for treatment of inflammatory diseases. The total alkaloids are believed to be the active components responsible for anti-inflammation of Linderae Radix. Here, the total alkaloids of Linderae Radix were extracted and isolated, including 12 isoquinoline alkaloids and 1 furan sesquiterpene. Within the alkaloids, norisoboldine, boldine, linderaline, isoboldine, reticuline, N-methyllaurotetanine, norjuziphine were found to be the major ingredients. In lipopolysaccharide-treated macrophage RAW 264.7 cells, application of Linderae Radix extract, or total alkaloids, suppressed the transcription of pro-inflammatory cytokines, interleukin-1β and interleukin-6. Out of the 12 alkaloids, norisoboldine, boldine, and isoboldine were tested in lipopolysaccharide-treated macrophages, and norisoboldine was the strongest alkaloid in suppressing the cytokine expressions. The current studies suggested that the identification of alkaloids from Linderae Radix could provide a plausible explanation for herbal therapeutic functions.

Pathogenesis of Hantaan Virus Infection in Sucking Mice

Gum Ryong Kim,Kelly T . Mckee,Ho Wang Lee 대한바이러스학회 1986 Journal of Bacteriology and Virology Vol.16 No.1

Surgical Considerations to Improve Recovery in Acute Spinal Cord Injury

Troy Q. Tabarestani,Nicholle E. Lewis,Margot Kelly-Hedrick,Nina Zhang,Brianna R. Cellini,Eric J. Marrotte,Theresa Williamson,Haichen Wang,Daniel T. Laskowitz,Timothy D. Faw,Muhammad M. Abd-El-Barr 대한척추신경외과학회 2022 Neurospine Vol.19 No.3

Acute traumatic spinal cord injury (SCI) can be a devastating and costly event for individuals, their families, and the health system as a whole. Prognosis is heavily dependent on the physical extent of the injury and the severity of neurological dysfunction. If not treated urgently, individuals can suffer exacerbated secondary injury cascades that may increase tissue injury and limit recovery. Initial recognition and rapid treatment of acute SCI are vital to limiting secondary injury, reducing morbidity, and providing the best chance of functional recovery. This article aims to review the pathophysiology of SCI and the most up-todate management of the acute traumatic SCI, specifically examining the modern approaches to surgical treatments along with the ethical limitations of research in this field.

Voxelwise lp-ntPET for detecting localized, transient dopamine release of unknown timing: Sensitivity Analysis and Application to Cigarette Smoking in the PET Scanner

Kim, Su Jin,Sullivan, Jenna M,Wang, Shuo,Cosgrove, Kelly P,Morris, Evan D BlackWell Publishing Ltd 2014 HUMAN BRAIN MAPPING Vol.35 No.9

<P>The “linear parametric neurotransmitter PET” (lp-ntPET) model estimates time variation in endogenous neurotransmitter levels from dynamic PET data. The pattern of dopamine (DA) change over time may be an important element of the brain's response to addictive substances such as cigarettes or alcohol. We have extended the lp-ntPET model from the original region of interest (ROI) - based implementation to be able to apply the model at the voxel level. The resulting endpoint is a dynamic image, or movie, of transient neurotransmitter changes. Simulations were performed to select threshold values to reduce the false positive rate when applied to real <SUP>11</SUP>C-raclopride PET data. We tested the new voxelwise method on simulated data, and finally, we applied it to <SUP>11</SUP>C-raclopride PET data of subjects smoking cigarettes in the PET scanner. In simulation, the temporal precision of neurotransmitter response was shown to be similar to that of ROI-based lp-ntPET (standard deviation ∼ 3 min). False positive rates for the voxelwise method were well controlled by combining a statistical threshold (the <I>F</I>-test) with a new spatial (cluster-size) thresholding operation. Sensitivity of detection for the new algorithm was greater than 80% for the case of short-lived DA changes that occur in subregions of the striatum as might be the case with cigarette smoking. Finally, in <SUP>11</SUP>C-raclopride PET data, DA movies reveal for the first time that different temporal patterns of the DA response to smoking may exist in different subregions of the striatum. These spatiotemporal patterns of neurotransmitter change created by voxelwise lp-ntPET may serve as novel biomarkers for addiction and/or treatment efficacy.</P>

Concurrent Isolation of 3 Distinct Cardiac Stem Cell Populations From a Single Human Heart Biopsy

Monsanto, Megan M.,White, Kevin S.,Kim, Taeyong,Wang, Bingyan J.,Fisher, Kristina,Ilves, Kelli,Khalafalla, Farid G.,Casillas, Alexandria,Broughton, Kathleen,Mohsin, Sadia,Dembitsky, Walter P.,Sussman, Grune & Stratton 2017 Circulation research Vol.121 No.2

<P><B><U>Rationale:</U></B></P><P>The relative actions and synergism between distinct myocardial-derived stem cell populations remain obscure. Ongoing debates on optimal cell population(s) for treatment of heart failure prompted implementation of a protocol for isolation of multiple stem cell populations from a single myocardial tissue sample to develop new insights for achieving myocardial regeneration.</P><P><B><U>Objective:</U></B></P><P>Establish a robust cardiac stem cell isolation and culture protocol to consistently generate 3 distinct stem cell populations from a single human heart biopsy.</P><P><B><U>Methods and Results:</U></B></P><P>Isolation of 3 endogenous cardiac stem cell populations was performed from human heart samples routinely discarded during implantation of a left ventricular assist device. Tissue explants were mechanically minced into 1 mm<SUP>3</SUP> pieces to minimize time exposure to collagenase digestion and preserve cell viability. Centrifugation removes large cardiomyocytes and tissue debris producing a single cell suspension that is sorted using magnetic-activated cell sorting technology. Initial sorting is based on tyrosine-protein kinase Kit (c-Kit) expression that enriches for 2 c-Kit<SUP>+</SUP> cell populations yielding a mixture of cardiac progenitor cells and endothelial progenitor cells. Flowthrough c-Kit<SUP>−</SUP> mesenchymal stem cells are positively selected by surface expression of markers CD90 and CD105. After 1 week of culture, the c-Kit<SUP>+</SUP> population is further enriched by selection for a CD133<SUP>+</SUP> endothelial progenitor cell population. Persistence of respective cell surface markers in vitro is confirmed both by flow cytometry and immunocytochemistry.</P><P><B><U>Conclusions:</U></B></P><P>Three distinct cardiac cell populations with individualized phenotypic properties consistent with cardiac progenitor cells, endothelial progenitor cells, and mesenchymal stem cells can be successfully concurrently isolated and expanded from a single tissue sample derived from human heart failure patients.</P>