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1.  Hyper-reactivity of Rabbits Sensitized with Bartonella bacilliformis 
Journal of Bacteriology  1966;92(3):769-779.
Mitchell, Paul D. (West Virginia University Medical Center, Morgantown), and John M. Slack. Hyper-reactivity of rabbits sensitized with Bartonella bacilliformis. J. Bacteriol. 92:769–779. 1966.—Sensitization with viable cells of Bartonella bacilliformis increased the susceptibility of rabbits to the lethality of subsequently administered Bartonella metabolites. In animals sensitized with 3 weekly doses of the organism, this susceptible state of hyper-reactivity was maximal between 4 and 14 days postsensitization (primary hyper-reactive state) and persisted for at least 4 weeks, after which the animals were nonreactive (tolerant state). However, on the 84th day, the susceptible state could once again be demonstrated (secondary hyper-reactive state). Animals sensitized with only 1 or 2 weekly doses of the organism were rendered nearly as susceptible, but the time interval between the primary and secondary states of hyper-reactivity was much shorter, indicating that the hyper-reactive states were dependent upon the degree of sensitization. Symptoms displayed by such animals demonstrated an association with endotoxic shock and an anaphylactic or immediate hypersensitive response, the reaction frequently being severe enough to lead to the death of the animal within 24 hr. The histological findings were those of the generalized Shwartzman phenomenon with indications of shock. Such hyper-reactive animals produced an early-occurring, precipitating antibody specific for the somatic, endotoxic component of various gram-positive microorganisms. Injection of sera from the hyper-reactive animals into normal, nonsensitized animals resulted in a passive, hyper-reactive state in the latter animals. A distinct relationship between the levels of specific antibody and the degree of demonstrable hyper-reactivity was observed. This relationship is discussed relative to the histological findings of the hyper-reactive animals.
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PMCID: PMC276321  PMID: 4958777
2.  SEROLOGY OF THE MIMA-HERELLEA GROUP AND THE GENUS MORAXELLA1 
Journal of Bacteriology  1964;87(4):900-909.
Mitchell, Paul D. (West Virginia University Medical Center, Morgantown), and Robert G. Burrell. Serology of the Mima-Herellea group and the genus Moraxella. J. Bacteriol. 87:900–909. 1964.—The identity of organisms which have been assigned to the Mima-Herellea group of the tribe Mimeae and their taxonomic position are uncertain. In considering the possible relationship of the Mima-Herellea group to the genus Moraxella, the approach used was the isolation and identification of representative antigenic constituents of strains designated Mima polymorpha, M. polymorpha var. oxidans, Herellea vaginicola, Moraxella lwoffi, M. liquefaciens, M. non-liquefaciens, and Bacterium anitratum. Cell-free extracts of sonically disrupted cells were used in these studies, and the precipitinogens derived by this method were considered to be of capsular and somatic origin. Identity among the strains was established by immunodiffusion, with immune sera and antigenic extracts. Heterologous and homologous reactions were performed with adsorbed and unadsorbed sera to verify the cases of identity. In every instance of homologous reaction, at least five distinct antigen-antibody systems were discernible within the Mima-Herellea group. However, as evidenced by heterologous studies, the demonstrable antigenic composition varied among the species and, in some instances, among the strains. M. polymorpha var. oxidans appeared to be serologically distinct from H. vaginicola and M. polymorpha, whereas strains of the latter two organisms were theorized to be closely related serologically. Serological cross-reactions in heterologous studies and reciprocal adsorption tests revealed the existence of a serological relationship between members of the Mima-Herellea group and the genus Moraxella. A tentative scheme of identity is postulated on the basis of these crossreactions and cultural and biochemical reactions among the designated strains of Herellea, Mima, Moraxella, and Bacterium.
PMCID: PMC277109  PMID: 14137629
3.  Peginterferon for Chronic Hepatitis C in Children affects Growth and Body Composition: Results from the Pediatric Study of Hepatitis C (PEDS-C) Trial 
Hepatology (Baltimore, Md.)  2012;56(2):523-531.
Background
Weight loss and changes in growth are noted in children treated with interferonα
Objectives
To prospectively determine changes in weight, height, body mass index and body composition during and after treatment of children with hepatitis C.
Methods
Children treated with PEG-IFNα2a +/− ribavirin in the PEDS-C trial underwent anthropometric measurements, DXA scan, dietary and activity assessments during and after treatment.
Results
114 (55% male) children mean age 11±3 years were randomized, and 107 received treatment for at least 24 weeks. Subjects were divided into 3 groups according to duration of treatment: 24 (N=14), 48 (N=82), or 72 (N=11) weeks. Decrements of up to 0.50 z score were observed for weight, height and BMI while on therapy among all groups (P≤0.01 compared to baseline). In the group treated for 48 weeks, 29 (33%) subjects had greater than 0.5 unit decrement in height-for-age Z score. While weight-for-age and BMI z scores returned to baseline after cessation of therapy, mean HAZ score was slower to rebound, still lower than baseline at 96 weeks post-therapy for the long treatment duration group (P=0.03) and lower than baseline in most children treated for 48 weeks. Percent body fat, fat-free mass z scores and triceps skinfold z scores decreased with therapy. Dietary energy intake and levels of physical activity did not change during treatment.
Conclusions
PEG-IFNα2a was associated with significant changes in body weight, linear growth, body mass index and body composition in children. These effects were generally reversible with cessation of therapy, although height-for-age z scores had not returned to baseline after 2 years of observation in many. Longer term growth data are needed among children treated for chronic HCV.
doi:10.1002/hep.25690
PMCID: PMC3382022  PMID: 22383118
4.  Characterization of Adherent Bacteroidales from Intestinal Biopsies of Children and Young Adults with Inflammatory Bowel Disease 
PLoS ONE  2013;8(6):e63686.
There is extensive evidence implicating the intestinal microbiota in inflammatory bowel disease [IBD], but no microbial agent has been identified as a sole causative agent. Bacteroidales are numerically dominant intestinal organisms that associate with the mucosal surface and have properties that both positively and negatively affect the host. To determine precise numbers and species of Bacteroidales adherent to the mucosal surface in IBD patients, we performed a comprehensive culture based analysis of intestinal biopsies from pediatric Crohn's disease [CD], ulcerative colitis [UC], and control subjects. We obtained biopsies from 94 patients and used multiplex PCR or 16S rDNA sequencing of Bacteroidales isolates for species identification. Eighteen different Bacteroidales species were identified in the study group, with up to ten different species per biopsy, a number higher than demonstrated using 16S rRNA gene sequencing methods. Species diversity was decreased in IBD compared to controls and with increasingly inflamed tissue. There were significant differences in predominant Bacteroidales species between biopsies from the three groups and from inflamed and uninflamed sites. Parabacteroides distasonis significantly decreased in inflamed tissue. All 373 Bacteroidales isolates collected in this study grew with mucin as the only utilizable carbon source suggesting this is a non-pathogenic feature of this bacterial order. Bacteroides fragilis isolates with the enterotoxin gene [bft], previously associated with flares of colitis, were not found more often at inflamed colonic sites or within IBD subjects. B. fragilis isolates with the ability to synthesize the immunomodulatory polysaccharide A [PSA], previously shown to be protective in murine models of colitis, were not detected more often from healthy versus inflamed tissue.
doi:10.1371/journal.pone.0063686
PMCID: PMC3679120  PMID: 23776434
5.  Risk Factors for Parenteral Nutrition–associated Liver Disease Following Surgical Therapy for Necrotizing Enterocolitis 
Objective
The aim of the study was to prospectively determine risk factors for the development of parenteral nutrition–associated liver disease (PNALD) in infants who underwent surgery for necrotizing enterocolitis (NEC), the most common cause of intestinal failure in children.
Patients and Methods
From February 2004 to February 2007, we diagnosed 464 infants with NEC, of whom 180 had surgery. One hundred twenty-seven patients were available for full analysis. PNALD was defined as serum direct bilirubin ≥2 mg/dL or ALT ≥2× the upper limit of normal in the absence of sepsis after ≥14 days of exposure to PN. Median
Results
Median gestational age was 26 weeks and 68% were boys. Seventy percent of the cohort developed PNALD and the incidence of PNALD varied significantly across the 6 study sites, ranging from 56% to 85% (P=0.05). Multivariable logistic regression analysis identified small-bowel resection or creation of jejunostomy (odds ratio [OR] 4.96, 95% confidence interval [CI] 1.97–12.51, P = 0.0007) and duration of PN in weeks (OR 2.37, 95% CI 1.56–3.60, P < 0.0001) as independent risk factors for PNALD. Preoperative exposure to PN was also associated with the development of PNALD; the risk of PNALD was 2.6 (95% CI 1.5–4.7; P = 0.001) times greater in patients with ≥4 weeks of preoperative PN compared with those with less preoperative PN use. Breast milk feedings, episodes of infection, and gestational age were not related to the development of PNALD.
Conclusions
The incidence of PNALD is high in infants with NEC undergoing surgical treatment. Risk factors for PNALD are related to signs of NEC severity, including the need for small-bowel resection or proximal jejunostomy, as well as longer exposure to PN. Identification of these and other risk factors can help in the design of clinical trials for the prevention and treatment of PNALD and for clinical assessment of patients with NEC and prolonged PN dependence.
doi:10.1097/MPG.0b013e31820e8396
PMCID: PMC3444282  PMID: 21464752
intestinal failure; jejunostomy; necrotizing enterocolitis; parenteral nutrition–associated liver disease; short-bowel syndrome
6.  A Pilot Study of Ketamine versus Midazolam/Fentanyl Sedation in Children Undergoing GI Endoscopy 
Background. Ketamine sedation has been found superior by physician report to traditional sedation regimens for pediatric endoscopy. Goal. To objectively compare sedation with ketamine versus midazolam/fentanyl for children undergoing gastrointestinal endoscopy. Study. Patients received one of two regimens and were independently monitored using a standardized rating scale. Results. There were 2 episodes of laryngospasm during ketamine sedation. Univariate analyses showed patients sedated with ketamine (n = 17) moved more (median 25% of procedure time versus 8%, P = .03) and required similar low levels of restraint (0.83% versus 0.25%, P = .4) as patients sedated with midazolam/fentanyl (n = 20). Age-adjusted analyses suggested that patients sedated with ketamine were comparably more quiet (P = .002). Conclusions. A pilot trial of ketamine at our institution was associated with episodes of laryngospasm. In addition, children sedated with ketamine moved and required restraint similarly to patients sedated with midazolam/fentanyl. Physician perceptions may be affected by the fact that children who received ketamine were less likely to vocalize distress.
doi:10.1155/2011/623710
PMCID: PMC3133434  PMID: 21760813
7.  Market-level assessment of the economic benefits of atrazine in the United States 
Pest Management Science  2014;70(11):1684-1696.
BACKGROUND
Atrazine and other triazine herbicides are widely used in US maize and sorghum production, yet the most recent market-level assessment of the economic benefits of atrazine is for market conditions prevalent in the early 1990s, before commercialization of transgenic crops. Grain markets have changed substantially since that time; for example, the size of the US maize market increased by 170% from 1990–1992 to 2007–2009. This paper reports a current assessment of the economic benefits of atrazine.
RESULTS
Yield increases and cost changes implied by triazine herbicides are projected to reduce maize prices by 7–8% and sorghum prices by 19–20%. Projected consumer benefits from lower prices range from $US 3.6 to 4.4 × 109 annually, with the net projected economic benefit for triazine herbicides to the US economy ranging from $US 2.9 to 3.4 × 109 annually because lower prices imply reduced producer income. Productivity gains from triazine herbicides maintain an estimated 270 000–390 000 ha of land in non-crop uses that generate environmental benefits not accounted for in this analysis.
CONCLUSION
Even in the current era, with transgenic varieties dominating crop production, atrazine and the other triazine herbicides continue to be a key part of maize and sorghum production and generate substantial economic benefits. © 2013 The Authors. PestManagement Science published by JohnWiley & Sons Ltd on behalf of Society of Chemical Industry.
doi:10.1002/ps.3703
PMCID: PMC4282455  PMID: 24318916
AGSIM; conservation tillage; maize; no-till; sorghum; triazine herbicides
8.  PerR Confers Phagocytic Killing Resistance and Allows Pharyngeal Colonization by Group A Streptococcus 
PLoS Pathogens  2008;4(9):e1000145.
The peroxide response transcriptional regulator, PerR, is thought to contribute to virulence of group A Streptococcus (GAS); however, the specific mechanism through which it enhances adaptation for survival in the human host remains unknown. Here, we identify a critical role of PerR-regulated gene expression in GAS phagocytosis resistance and in virulence during pharyngeal infection. Deletion of perR in M-type 3 strain 003Sm was associated with reduced resistance to phagocytic killing in human blood and by murine macrophages in vitro. The increased phagocytic killing of the perR mutant was abrogated in the presence of the general oxidative burst inhibitor diphenyleneiodonium chloride (DPI), a result that suggests PerR-dependent gene expression counteracts the phagocyte oxidative burst. Moreover, an isogenic perR mutant was severely attenuated in a baboon model of GAS pharyngitis. In competitive infection experiments, the perR mutant was cleared from two animals at 24 h and from four of five animals by day 14, in sharp contrast to wild-type bacteria that persisted in the same five animals for 28 to 42 d. GAS genomic microarrays were used to compare wild-type and perR mutant transcriptomes in order to characterize the PerR regulon of GAS. These studies identified 42 PerR-dependent loci, the majority of which had not been previously recognized. Surprisingly, a large proportion of these loci are involved in sugar utilization and transport, in addition to oxidative stress adaptive responses and virulence. This finding suggests a novel role for PerR in mediating sugar uptake and utilization that, together with phagocytic killing resistance, may contribute to GAS fitness in the infected host. We conclude that PerR controls expression of a diverse regulon that enhances GAS resistance to phagocytic killing and allows adaptation for survival in the pharynx.
Author Summary
Group A Streptococcus (GAS) is the leading cause of bacterial pharyngitis (strep throat) in children. It is also associated with the life-threatening conditions of necrotizing fasciitis, streptococcal toxic shock, and the post-streptococcal autoimmune syndrome of rheumatic fever and heart disease. The peroxide response regulator PerR is thought to enhance GAS pathogenesis by coordinating adaptive responses of the bacteria in oxidative environments, but its specific contribution to GAS adaptation and virulence at various host sites during infection is poorly understood. In studies comparing phagocytic killing resistance of wild-type and a perR mutant strain of GAS, we find that PerR contributes to bacterial survival in the oxidative environment of phagocytes either during growth in human blood or during interaction with mouse macrophages. Moreover, our studies in a primate model of human pharyngitis suggest that PerR is critical for pharyngeal infection, as PerR mutant bacteria were able to establish infection in one of five inoculated animals in contrast to wild-type bacteria, which established infection in all five animals used. Initial investigation into the genes controlled by PerR in GAS identified a range of bacterial products that may contribute to GAS survival and virulence during infection.
doi:10.1371/journal.ppat.1000145
PMCID: PMC2518855  PMID: 18773116
9.  Leptotrichia amnionii sp. nov., a Novel Bacterium Isolated from the Amniotic Fluid of a Woman after Intrauterine Fetal Demise 
Journal of Clinical Microbiology  2002;40(9):3346-3349.
A novel bacterium was isolated and characterized from the amniotic fluid of a woman who experienced intrauterine fetal demise in the second trimester of pregnancy. The bacterium was a slow-growing, gram-negative anaerobic coccobacillus belonging to the genus Leptotrichia. Unlike Leptotrichia sanguinegens, the isolate did not grow in chopped-meat glucose broth or on sheep blood agar upon subculturing. The isolate was characterized by sequencing and analyzing its 16S rRNA gene. The 1,493-bp 16S ribosomal DNA sequence had only 96% homology with L. sanguinegens. Several phylogenetic analyses indicated that L. amnionii is a distinct species and most closely related to L. sanguiegens.
doi:10.1128/JCM.40.9.3346-3349.2002
PMCID: PMC130742  PMID: 12202577
10.  Immunoglobulin M Capture Assay for Serologic Confirmation of Early Lyme Disease: Analysis of Immune Complexes with Biotinylated Borrelia burgdorferi Sonicate Enhanced with Flagellin Peptide Epitope 
Journal of Clinical Microbiology  1998;36(4):1074-1080.
We previously reported on the efficacy of the enzyme-linked immunoglobulin M capture immune complex (IC) biotinylated antigen assay (EMIBA) for the seroconfirmation of early Lyme disease and active infection with Borrelia burgdorferi. In earlier work we identified non-cross-reacting epitopes of a number of B. burgdorferi proteins, including flagellin. We now report on an improvement in the performance of EMIBA with the addition of a biotinylated form of a synthetic non-cross-reacting immunodominant flagellin peptide to the biotinylated B. burgdorferi B31 sonicate antigen source with the avidin-biotinylated peroxidase complex detection system used in our recently developed indirect IgM-capture immune complex-based assay (EMIBA). As in our previous studies, the enzyme-linked immunosorbent assay (ELISA) reactivities of antibodies liberated from circulating ICs (by EMIBA) were compared with those of antibodies in unprocessed serum (antibodies found free in the serum, thus as an IgM-capture ELISA, but not EMIBA, because the antibodies were not liberated from ICs), the sample usually used in standard ELISAs and Western blot assays. The addition of the flagellin epitope enhanced the ELISA signal obtained with untreated sera from many Lyme disease patients but not from healthy controls. In tests with both free antibodies and ICs, with or without the addition of the flagellin epitope to the sonicate, we found the most advantageous combination was IC as the source of antibodies and sonicate plus the flagellin epitope as the antigen. In a blinded study of sera obtained from patients with early and later-phase Lyme disease, EMIBA with the enhanced antigenic preparation compared favorably with other serologic assays, especially for the confirmation of early disease.
PMCID: PMC104692  PMID: 9542940

Results 1-11 (11)