Publications by authors named "Rebecca Kelley"

12 Publications

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Gastroparesis with concomitant gastrointestinal dysmotility is not a contraindication for per-oral pyloromyotomy (POP).

Surg Endosc 2021 Oct 12. Epub 2021 Oct 12.

Digestive Disease and Surgical Institute, Cleveland Clinic, Cleveland, OH, USA.

Introduction: Per-oral pyloromyotomy (POP or G-POEM) provides significant short-term improvements in symptoms and objective emptying for patients with medically refractory gastroparesis, but it is unclear if patients with gastroparesis and co-existing dysmotility (small bowel or colonic delay) also benefit. In this study, we used wireless motility capsule (WMC) data to measure outcomes in patients with isolated gastroparesis (GP) and gastroparesis with co-existing dysmotility (GP + Dys) who underwent POP.

Methods: We retrospectively analyzed patients who had POP and completed WMC data during their evaluation of intestinal dysmotility. WMC data were reviewed to identify patients who demonstrated isolated GP or GP + Dys. Each patient's pre-op and post-op Gastroparesis Cardinal Symptom Index (GCSI) and 4-h solid-phase scintigraphy gastric emptying studies (GES) scores were compared to evaluate improvement.

Results: Of the entire cohort (n = 73), 89% were female with a mean age of 47.0 ± 15.0 years old. Gastroparesis etiologies were divided among idiopathic (54.8%), diabetic (26%), postsurgical (8.2%), autoimmune (5.5%), and multifactorial (5.5%). Forty-one patients (56%) had GP and 32 patients (44%) had GP + Dys. GCSI improved after POP whether the patient had isolated GP (- 12.31, p < 0.001) or GP + Dys (- 9.58, p < 0.001); however, there was no significant difference in total GCSI improvement between the two groups. A subset of patients had postoperative GES available (n = 47). In the isolated GP and GP + Dys cohorts, 15/28 (54%) and 12/19 (63%) patients had normal post-op 4-h GES, respectively, but no statistical difference between the two groups.

Conclusion: Patients with medically refractory gastroparesis with and without concomitant gastrointestinal dysmotility show short-term subjective and objective improvement after POP. Concomitant small bowel or colonic dysmotility should not deter physicians from offering POP in carefully selected patients with gastroparesis.
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http://dx.doi.org/10.1007/s00464-021-08756-9DOI Listing
October 2021

Individual culture and atmospheric oxygen during culture affect mouse preimplantation embryo metabolism and post-implantation development.

Reprod Biomed Online 2019 Jul 11;39(1):3-18. Epub 2019 Mar 11.

School of BioSciences, The University of Melbourne, Parkville Victoria 3010, Australia. Electronic address:

Research Question: Does single embryo culture under atmospheric or reduced oxygen alter preimplantation metabolism and post-implantation development compared with culture in groups?

Design: Mouse embryos were cultured under 5% or 20% oxygen, individually or in groups of 10. Spent media were analysed after 48, 72 and 96 h of culture. Blastocysts were assessed by outgrowth assay or transferred to pseudo-pregnant recipients, and fetal and placental weight, length and morphology were assessed.

Results: Compared with group culture, individually cultured blastocysts had lower net consumption of glucose and aspartate and higher glutamate production. Atmospheric oxygen reduced uptake of glucose and aspartate and increased production of glutamate and ornithine compared with 5% oxygen. Combining 20% oxygen and single culture resulted in further metabolic changes: decreased leucine, methionine and threonine consumption. Under 5% oxygen, individual culture decreased placental labyrinth area but had no other effects on fetal and placental development or outgrowth size compared with group culture. Under 20% oxygen, however, individual culture reduced outgrowth size and fetal and placental weight compared with group-cultured embryos.

Conclusions: Preimplantation metabolism of glucose and amino acids is altered by both oxygen and individual culture, and fetal weight is reduced by individual culture under atmospheric oxygen but not 5% oxygen. This study raises concerns regarding the increasing prevalence of single embryo culture in human IVF and adds to the existing evidence regarding the detrimental effects of atmospheric oxygen during embryo culture. Furthermore, these data demonstrate the cumulative nature of stress during embryo culture and highlight the importance of optimizing each element of the culture system.
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http://dx.doi.org/10.1016/j.rbmo.2019.03.102DOI Listing
July 2019

A Tale of Two Valleys: Disparity in Sin Nombre Virus Antibody Reactivity Between Neighboring Mojave Desert Communities.

Vector Borne Zoonotic Dis 2019 04 1;19(4):290-294. Epub 2018 Dec 1.

1 Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, California.

Introduction: Hantaviruses are a group of globally distributed rodent-associated viruses, some of which are responsible for human morbidity and mortality. Sin Nombre orthohantavirus, a particularly virulent species of hantavirus associated with Peromyscus spp. mice, is actively monitored by the Department of Public Health in California (CDPH). Recently, CDPH documented high (40%) seroprevalence in a potentially novel reservoir species, the cactus mouse (Peromyscus eremicus) in Death Valley National Park.

Methods: This study was performed in the extremely isolated Mojave Desert Amargosa River valley region of southeastern Inyo County, California, 105 km from Death Valley, approximately over the same time interval as the CDPH work in Death Valley (between 2011 and 2016). Similar rodent species were captured as in Death Valley and were tested for select hantaviruses using serology and RT-PCR to assess risk to human health and the conservation of the endemic endangered Amargosa vole.

Results: Among 192 rodents tested, including 56 Peromyscus spp., only one seropositive harvest mouse (Reithrodontomys megalotis) was detected.

Discussion: These data highlight the heterogeneity in the prevalence of hantavirus infection even among nearby desert communities and suggest that further studies of hantavirus persistence in desert environments are needed to more accurately inform the risks to public health and wildlife conservation.
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http://dx.doi.org/10.1089/vbz.2018.2341DOI Listing
April 2019

Anti-Müllerian hormone overexpression restricts preantral ovarian follicle survival.

J Endocrinol 2018 05 14;237(2):153-163. Epub 2018 Mar 14.

Department of AnatomySchool of Biomedical Sciences, University of Otago, Dunedin, New Zealand.

Anti-Müllerian hormone (AMH) is an ovarian regulator that affects folliculogenesis. AMH inhibits the developmental activation of the dormant primordial follicles and the oocyte within. In more mature follicles, AMH reduces granulosa cell sensitivity to follicle-stimulating hormone (FSH). We examined the effects of AMH overexpression on the stages of ovarian folliculogenesis, and the development of embryos, with a transgenic mouse that overexpresses human AMH in central nervous system neurons under the control of the mouse Thy1.2 promoter ( mice). These mice are severely sub-fertile, despite relatively normal ovulation rates. The embryos of females exhibited delayed preimplantation development and extensive mid-gestation fetal resorption. Young mouse ovaries exhibited only a slight reduction in the rate of primordial follicle activation but large declines in the number of developing follicles surviving past the primary stage. It was expected that mice would retain more primordial follicles as they aged, but at 5 months, their number was significantly reduced relative to wild-type females. These data indicate that moderate elevations in AMH levels can severely restrict reproductive output and the number of developing follicles in the ovary. This evidence suggests that early antral follicles are a target for AMH signaling, which may regulate early follicle survival.
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http://dx.doi.org/10.1530/JOE-18-0005DOI Listing
May 2018

Addition of interleukin-6 to mouse embryo culture increases blastocyst cell number and influences the inner cell mass to trophectoderm ratio.

Clin Exp Reprod Med 2017 Sep 26;44(3):119-125. Epub 2017 Sep 26.

School of Biosciences, University of Melbourne, Parkville, Australia.

Objective: culture of preimplantation embryos is improved by grouping embryos together in a drop of media. Individually cultured embryos are deprived of paracrine factors; with this in mind, we investigated whether the addition of a single embryo-secreted factor, interleukin-6 (IL-6), could improve the development of individually cultured embryos.

Methods: Mouse embryos were cultured individually in 2 µL of G1/G2 media in 5% oxygen and supplemented with a range of doses of recombinant mouse or human IL-6.

Results: Mouse IL-6 increased hatching at doses of 0.01 and 10 ng/mL compared to the control (93% and 93% vs. 78%, <0.05) and increased the total number of cells at a dose of 0.1 ng/mL compared to the control (101.95±3.36 vs. 91.31±3.33, <0.05). In contrast, the highest dose of 100 ng/mL reduced the total number of cells (79.86±3.29, <0.05). Supplementation with human IL-6 had a different effect, with no change in hatching or total cell numbers, but an increase in the percentage of inner cell mass per embryo at doses of 0.1, 1, and 100 ng/mL compared to the control (22.9%±1.1%, 23.3%±1.1%, and 23.1%±1.1% vs. 19.5%±1.0%, <0.05).

Conclusion: These data show that IL-6 improved mouse embryo development when cultured individually in complex media; however, an excess of IL-6 may be detrimental. Additionally, these data indicate that there is some cross-species benefit of human IL-6 for mouse embryos, but possibly through a different mechanism than for mouse IL-6.
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http://dx.doi.org/10.5653/cerm.2017.44.3.119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636923PMC
September 2017

In vitro culture of individual mouse preimplantation embryos: the role of embryo density, microwells, oxygen, timing and conditioned media.

Reprod Biomed Online 2017 May 15;34(5):441-454. Epub 2017 Feb 15.

School of BioSciences, The University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address:

Single embryo culture is suboptimal compared with group culture, but necessary for embryo monitoring, and culture systems should be improved for single embryos. Pronucleate mouse embryos were used to assess the effect of culture conditions on single embryo development. Single culture either before or after compaction reduced cell numbers (112.2 ± 3.1; 110.2 ± 3.5) compared with group culture throughout (127.0 ± 3.4; P < 0.05). Reduction of media volume from 20 µl to 2 µl increased blastocyst cell numbers in single embryos cultured in 5% oxygen (84.4 ± 3.2 versus 97.8 ± 2.8; P < 0.05), but not in 20% oxygen (55.2 ± 2.9 versus 57.1 ± 2.8). Culture in microwell plates for the EmbryoScope and Primo Vision time-lapse systems changed cleavage timings and increased inner cell mass cell number (24.1 ± 1.0; 23.4 ± 1.2) compared with a 2 µl microdrop (18.4 ± 1.0; P < 0.05). Addition of embryo-conditioned media to single embryos increased hatching rate and blastocyst cell number (91.5 ± 4.7 versus 113.1 ± 4.4; P < 0.01). Single culture before or after compaction is therefore detrimental; oxygen, media volume and microwells influence single embryo development; and embryo-conditioned media may substitute for group culture.
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http://dx.doi.org/10.1016/j.rbmo.2017.02.001DOI Listing
May 2017

Combined effects of individual culture and atmospheric oxygen on preimplantation mouse embryos in vitro.

Reprod Biomed Online 2016 Nov 20;33(5):537-549. Epub 2016 Aug 20.

School of BioSciences, The University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address:

Embryos are routinely cultured individually, although this can reduce blastocyst development. Culture in atmospheric (20%) oxygen is also common, despite multiple detrimental effects on embryos. Although frequently occurring together, the consequences of this combination are unknown. Mouse embryos were cultured individually or grouped, under physiological (5%) or atmospheric (20%) oxygen. Embryos were assessed by time-lapse and blastocyst cell allocation. Compared with the control group (5% oxygen group culture), 5-cell cleavage (t5) was delayed in 5% oxygen individual culture and 20% oxygen group culture (59.91 ± 0.23, 60.70 ± 0.29, 63.06 ± 0.32 h post-HCG respectively, P < 0.05). Embryos in 20% oxygen individual culture were delayed earlier (3-cell cleavage), and at t5 cleaved later than embryos in other treatments (66.01 ± 0.40 h, P < 0.001), this delay persisting to blastocyst hatching. Compared with controls, hatching rate and cells per blastocyst were reduced in 5% oxygen single culture and 20% oxygen group culture (134.1 ± 3.4, 104.5 ± 3.2, 73.4 ± 2.2 cells, P < 0.001), and were further reduced in 20% oxygen individual culture (57.0 ± 2.8 cells, P < 0.001), as was percentage inner cell mass. These data indicate combining individual culture and 20% oxygen is detrimental to embryo development.
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http://dx.doi.org/10.1016/j.rbmo.2016.08.003DOI Listing
November 2016

Development and comparison of two multi-residue methods for the analysis of select pesticides in honey bees, pollen, and wax by gas chromatography-quadrupole mass spectrometry.

Talanta 2015 Aug 23;140:81-87. Epub 2015 Mar 23.

Center for Fisheries, Aquaculture and Aquatic Sciences, Department of Zoology, Southern Illinois University, 171 Life Science II, Carbondale, IL 62901, USA. Electronic address:

One of the hypotheses that may help explain the loss of honey bee colonies worldwide is the increasing potential for exposure of honey bees to complex mixtures of pesticides. To better understand this phenomenon, two multi-residue methods based on different extraction and cleanup procedures have been developed, and compared for the determination of 11 relevant pesticides in honey bees, pollen, and wax by gas chromatography-quadrupole mass spectrometry. Sample preparatory methods included solvent extraction followed by gel permeation chromatography (GPC) cleanup and cleanup using a dispersive solid-phase extraction with zirconium-based sorbents (Z-Sep). Matrix effects, method detection limits, recoveries, and reproducibility were evaluated and compared. Method detection limits (MDL) of the pesticides for the GPC method in honey bees, pollen, and wax ranged from 0.65 to 5.92 ng/g dw, 0.56 to 6.61 ng/g dw, and 0.40 to 8.30 ng/g dw, respectively, while MDLs for the Z-Sep method were from 0.33 to 4.47 ng/g dw, 0.42 to 5.37 ng/g dw, and 0.51 to 5.34 ng/g dw, respectively. The mean recoveries in all matrices and at three spiking concentrations ranged from 64.4% to 149.5% and 71.9% to 126.2% for the GPC and Z-Sep methods, with relative standard deviation between 1.5-25.3% and 1.3-15.9%, respectively. The results showed that the Z-Sep method was more suitable for the determination of the target pesticides, especially chlorothalonil, in bee hive samples. The Z-Sep method was then validated using a series of field-collected bee hive samples taken from honey bee colonies in Virginia.
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http://dx.doi.org/10.1016/j.talanta.2015.03.031DOI Listing
August 2015

Cooperativity of imprinted genes inactivated by acquired chromosome 20q deletions.

J Clin Invest 2013 May 1;123(5):2169-82. Epub 2013 Apr 1.

Cambridge Institute for Medical Research and Wellcome Trust/MRC Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.

Large regions of recurrent genomic loss are common in cancers; however, with a few well-characterized exceptions, how they contribute to tumor pathogenesis remains largely obscure. Here we identified primate-restricted imprinting of a gene cluster on chromosome 20 in the region commonly deleted in chronic myeloid malignancies. We showed that a single heterozygous 20q deletion consistently resulted in the complete loss of expression of the imprinted genes L3MBTL1 and SGK2, indicative of a pathogenetic role for loss of the active paternally inherited locus. Concomitant loss of both L3MBTL1 and SGK2 dysregulated erythropoiesis and megakaryopoiesis, 2 lineages commonly affected in chronic myeloid malignancies, with distinct consequences in each lineage. We demonstrated that L3MBTL1 and SGK2 collaborated in the transcriptional regulation of MYC by influencing different aspects of chromatin structure. L3MBTL1 is known to regulate nucleosomal compaction, and we here showed that SGK2 inactivated BRG1, a key ATP-dependent helicase within the SWI/SNF complex that regulates nucleosomal positioning. These results demonstrate a link between an imprinted gene cluster and malignancy, reveal a new pathogenetic mechanism associated with acquired regions of genomic loss, and underline the complex molecular and cellular consequences of "simple" cancer-associated chromosome deletions.
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http://dx.doi.org/10.1172/JCI66113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635733PMC
May 2013

Analysis of persistent halogenated hydrocarbons in fish feeds containing fish oil and other alternative lipid sources.

Talanta 2011 Sep 12;85(3):1291-7. Epub 2011 Jun 12.

State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou, China.

A trade-off exists between beneficial n-3 long-chain polyunsaturated acids and toxic persistent halogenated hydrocarbons (PHHs), both of which primarily originate from fish oil commonly used in fish feeds. Alternative lipid sources are being investigated for use in fish feeds to reduce harmful contaminant accumulation, hence, research is needed to evaluate PHHs in fish feeds with various lipid compositions. An analytical method was developed for PHHs including nine organochlorine insecticides (OCPs), 26 polychlorinated biphenyls (PCBs) and seven polybrominated diphenyl ethers (PBDEs) in fish feeds with differing proportions of fish oils and alternative lipid sources by GC-ECD after accelerated solvent extraction, gel permeation chromatography (GPC), and sulfuric acid cleanup. The GPC removed the majority of the neutral lipids and sulfuric acid treatment effectively destroyed the polar lipids. Thus, the combination of the two methods removed approximately 99.7% of the lipids in the extracts. The method detection limits were less than 5 ng/g dry weight (dw) for most PHHs, while recoveries were 75-118%, 67-105%, 69-92%, 63-100% and 94-144% with relative standard deviations of 0.2-39%, 0.3-20%, 0.5-12%, 1.5-18% and 1.5-15% for PHHs in five types of fish feeds made from different lipid sources. Although the source of lipid showed no impact on cleanup efficiency and the developed method worked well for all feeds, fish feeds with 100% fish oil contained background PHHs and more interference than feeds containing alternative lipids.
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http://dx.doi.org/10.1016/j.talanta.2011.06.005DOI Listing
September 2011

Recombinant human follicle-stimulating hormone alters maternal ovarian hormone concentrations and the uterus and perturbs fetal development in mice.

Am J Physiol Endocrinol Metab 2006 Oct 23;291(4):E761-70. Epub 2006 May 23.

Research Centre for Reproductive Health, Discipline of Obstetrics & Gynaecology, School of Paediatrics and Reproductive Health, University of Adelaide, South Australia, Australia.

Gonadotropins are routinely administered to produce multiple oocytes for clinical in vitro fertilization (IVF) treatment, laboratory research, and livestock industries. Studies in mice have shown gonadotropin stimulation using equine chorionic gonadotropin (eCG) affects the endometrium, implantation, and fetal development. Evidence from clinical studies also indicates that stimulation with recombinant human follicle-stimulating hormone (rhFSH) may be detrimental to the endometrium and implantation rates. We investigated the effect of rhFSH in mice on maternal plasma hormone concentrations and uterine gene and protein expression and the effect of a stimulated maternal environment on pregnancy. Adult females were stimulated with rhFSH or eCG, followed by human chorionic gonadotropin (hCG). On day 4 of pseudopregnancy, mice either had embryos transferred to the uterus or were killed, and blood and uterine samples were collected. Pregnancy outcomes were examined on day 15. Gonadotropin stimulation increased plasma progesterone concentrations on day 4 compared with controls, whereas estradiol concentrations were unaffected. Stimulation also reduced uterine leukemia inhibitory factor (Lif) mRNA, but the expression of estrogen and progesterone receptors (Esr1 and Pgr), homeobox gene Hoxa10, and Vegf mRNA were unchanged. Furthermore, distribution of uterine PGR protein expression was altered by stimulation, but LIF protein was unchanged. Stimulated embryo transfer recipients had lower pregnancy rates than controls, and fetuses from the rhFSH group had reduced weight, length, and maturity. These results demonstrate that gonadotropin stimulation with rhFSH or eCG alters the preimplantation maternal environment, which results in reduced pregnancy rates and fetal development in the mouse.
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http://dx.doi.org/10.1152/ajpendo.00079.2006DOI Listing
October 2006

Effect of culturing mouse embryos under different oxygen concentrations on subsequent fetal and placental development.

J Physiol 2006 Apr 16;572(Pt 1):87-96. Epub 2006 Feb 16.

Department of Obstetrics and Gynaecology, University of Adelaide, Level 4, Maternity Building, The Queen Elizabeth Hospital, Woodville Road, Woodville, South Australia, 5011 Australia.

The oxygen concentration used during embryo culture can influence embryo development and quality. Reducing the oxygen concentration in the atmosphere to 2% during post-compaction culture of mouse embryos perturbs embryonic gene expression. This study examined the effect of culturing mouse embryos under different oxygen concentrations on subsequent fetal and placental development. Embryos were cultured from the zygote to morula stage under 7% oxygen, followed by 20, 7 or 2% oxygen to the blastocyst stage. Cultured and in vivo developed blastocysts were transferred into pseudopregnant recipients. Fetal and placental outcomes were analysed at day 18 of pregnancy. Implantation rate was not influenced by embryo culture conditions, but resorption rates were increased in embryos cultured under 2% oxygen, compared with 7% oxygen. Day 18 fetal weights were reduced following culture under 2%, compared with 7 or 20% oxygen, or in vivo development. Placental weight was not influenced by culture conditions. No differences in the proportion of junctional or labyrinthine exchange regions within the placenta or the morphometry of the labyrinthine region were detected. Surface density (surface area/gram labyrinth) of trophoblast available for exchange was reduced in placentas developed from embryos cultured under 2% oxygen, compared with 7% oxygen. Placental gene expression of Slc2a1, Slc2a3, Igf2, Igf2r and H19 was not influenced by oxygen conditions during embryo culture. Thus, exposure to 2% oxygen during post-compaction pre-implantation embryo development has adverse consequences for fetal development in the mouse. Oxygen is a significant component of the embryonic environment and reductions in oxygen availability can influence both embryonic gene expression and subsequent fetal development.
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http://dx.doi.org/10.1113/jphysiol.2005.102681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779635PMC
April 2006
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