Papers by Sanford Feldman
A2A adenosine receptor mediates suppression in a mouse model of colitis (39.1)
The Journal of Immunology
Background: Adenosine accumulates in inflamed tissue and can suppress proliferation and cytokine ... more Background: Adenosine accumulates in inflamed tissue and can suppress proliferation and cytokine production in helper T cells (Th). Th cells from mice lacking the A2A Adenosine Receptor (A2AAR-/-) do not function properly in the CD45RB transfer model of colitis. Methods: To examine the role of A2AAR in regulating colitis, we tested colonic myeloperoxidase (MPO) activity after adoptive transfer of Th cell susbsets from wildtype or A2AAR-/- mice. Th cells from mesenteric lymph nodes (MLN) of colitic mice were treated with an A2AAR agonist to assess effects on cytokine production. To investigate the role of A2AAR on myeloid cells in the CD45RB model of colitis, we adoptively transferred wildtype Th cells into RAG1/A2AAR double knockout (DKO) mice. Results: Colons of mice that received A2AAR-/- CD45RBhi cells with wildtype or A2AAR-/- CD45RBlo Treg had significantly greater MPO activity than mice that received wildtype CD45RBhi and CD45RBlo cells. Cytokine production by MLN Th cells fro...
Spontaneous Autoimmune Gastritis, Hypochlorhydria and Bacterial Overgrowth in the Ileitis-Prone, SAMP1/Yit Mice
Gastroenterology, 2011
Journal of Clinical Microbiology, 1999
Histopathologic evaluation combined with a period of immunosuppression has been the standard proc... more Histopathologic evaluation combined with a period of immunosuppression has been the standard procedure for detection of Pneumocystis carinii in commercial rat colonies. Variation in induction regimens and in the sensitivity of detection methods may result in underreporting of the presence of P. carinii in breeding colonies or delay its detection. In the present study, methylprednisolone and cyclophosphamide were evaluated for the ability to induce P. carinii infection in rats from an enzootically infected commercial barrier colony. The presence of P. carinii was detected by histopathologic methods and by amplification of a targeted region of the P. carinii thymidylate synthase gene by PCR over the 8-week study period. Sera taken from rats prior to either induction regimen were evaluated for the presence of P. carinii -specific antibodies by the immunoblotting technique. Few significant differences in ability to induce organism burden or in histopathology were observed between the tw...
PloS one, 2015
DNA-paramagnetic silica bead aggregation in a rotating magnetic field facilitates the quantificat... more DNA-paramagnetic silica bead aggregation in a rotating magnetic field facilitates the quantification of DNA with femtogram sensitivity, but yields no sequence-specific information. Here we provide an original description of aggregation inhibition for the detection of DNA and RNA in a sequence-specific manner following loop-mediated isothermal amplification (LAMP). The fragments generated via LAMP fail to induce chaotrope-mediated bead aggregation; however, due to their ability to passivate the bead surface, they effectively inhibit bead aggregation by longer 'trigger' DNA. We demonstrate the utility of aggregation inhibition as a method for the detection of bacterial and viral pathogens with sensitivity that approaches single copies of the target. We successfully use this methodology for the detection of notable food-borne pathogens Escherichia coli O157:H7 and Salmonella enterica, as well as Rift Valley fever virus, a weaponizable virus of national security concern. We also...
Journal of the American Association for Laboratory Animal Science : JAALAS, 2014
We used high-fidelity PCR to amplify a portion of the small ribosomal subunit (18S rRNA) of Pseud... more We used high-fidelity PCR to amplify a portion of the small ribosomal subunit (18S rRNA) of Pseudocapillaroides xenopi, a nematode that parasitizes the skin of Xenopus laevis. The 1113-bp amplicon was cloned, sequenced, and aligned with sequences from 22 other nematodes in the order Trichocephalida; Caenorhabditis elegans was used as the outgroup. Maximum-likelihood and Bayesian inference phylogenetic analyses clustered P. xenopi in a clade containing only members of the genus Capillaria. Our analyses support the following taxonomic relationships: 1) members of the family Trichuridae form a clade distinct from those in the family Trichocephalida; 2) members of the genera Trichuris and Capillaria form 2 distinct clades within the family Trichuridae; and 3) the genus Trichuris includes 2 distinct clades, one representing parasites that infect herbivores and the other representing parasites that infect omnivores and carnivores. Using 18S rRNA sequence unique to P. xenopi, we developed ...
Surgical Infections, 2014
Background: Anastomotic leak after rectal resection carries substantial morbidity and mortality. ... more Background: Anastomotic leak after rectal resection carries substantial morbidity and mortality. A diverting ileostomy is beneficial for high-risk anastomoses, but its creation and reversal carry a surgical risk in addition to that of resection itself. We sought an alternative method for managing complications of rectal anastomosis. Methods: We developed an endoluminal negative-pressure technology with a diverting proximal sump, and hypothesized that it would close anastomotic disruptions in pigs. We performed rectal resections on pigs, with primary anastomoses and the creation of an anastomotic defect. In animals in the treatment group we inserted an endoluminal negative-pressure device and kept it at a low level of continuous suction for 5 d. No device was inserted in a control group of animals. After the 5-d period of treatment we evaluated the anastomoses in both the treatment and control groups of animals for leakage, using contrast enemas. Specimens of anastomosed rectum were evaluated histologically for mucosal integrity and for the location and density of inflammatory responses. Results: Fourteen pigs were assigned to either the treatment (n = 10) or control (n = 4) group. Of the pigs in the treatment group, 90% had complete closure of their rectal defect, as compared with 25% of the animals in the control group (w 2 test, p = 0.04). The animals in the treatment group had only minimal mucosal and serosal inflammation, whereas those in the control group had extensive mucosal damage with associated serositis. Conclusions: Endoluminal negative-pressure therapy was well-tolerated and led to successful closure of 90% of the anastomic rectal defects in the treatment group of animals in the present study. Additional evaluation of this therapy is warranted.
Endoluminal vacuum therapy for gastrojejunal anastomotic leaks after Roux-en-Y gastric bypass: A pilot study in a swine model
Journal of the American College of Surgeons, 2012
Background Roux-en-Y gastric bypass (RYGB) consistently produces the most sustainable weight loss... more Background Roux-en-Y gastric bypass (RYGB) consistently produces the most sustainable weight loss among common interventions for morbid obesity. Anastomotic leaks at the gastrojejunal (GJ) connection result in severe morbidity. We apply endoluminal negative pressure vacuum devices (EVD) to heal anastomotic leaks in a swine model.
Journal of Clinical Investigation, 2000
CD18-deficient mice (CD18 -/-mice) have a severe leukocyte recruitment defect in some organs, and... more CD18-deficient mice (CD18 -/-mice) have a severe leukocyte recruitment defect in some organs, and no detectable defect in other models. Mice lacking E-selectin (CD62E -/-mice) have either no defect or a mild defect of neutrophil infiltration, depending on the model. CD18 -/-CD62E -/-, but not CD18 -/-CD62P -/-, mice generated by crossbreeding failed to thrive, reaching a maximum body weight of 10-15 grams. To explore the mechanisms underlying reduced viability, we investigated lethally irradiated CD62E -/-mice that were reconstituted with CD18 -/-bone marrow. These mice, but not singlemutant controls, showed tenfold-increased rolling velocities in a TNF-α-induced model of inflammation. Leukocyte adhesion efficiency in CD18 -/-CD62E -/-mice was reduced by 95%, and hematopoiesis was drastically altered, including severe bone marrow and blood neutrophilia and elevated G-CSF and GM-CSF levels. The greatly reduced viability of CD18 -/-CD62E -/-mice appears to result from an inability to mount an adequate inflammatory response. Our data show that cooperation between E-selectin and CD18 integrins is necessary for neutrophil recruitment and that alternative adhesion pathways cannot compensate for the loss of these molecules.
Clinical and Translational Science, 2014
Anastomotic leaks are a dreaded surgical complication following colorectal operations. Creation o... more Anastomotic leaks are a dreaded surgical complication following colorectal operations. Creation of a temporary proximal diverting ileostomy is used in high-risk anastomoses, however, additional surgical risk is accumulated with its creation and reversal. Endoluminal vacuum therapy has been shown to seal anastomotic defects in the prophylactic setting in a pig model and we hypothesized it could be utilized in a delayed fashion to rescue subjects with an active anastomotic leak. Yorkshire pigs underwent rectal resection, intentional leak confirmed by fluoroscopy, and endoluminal vacuum therapy device placement to low continuous suction. Following treatment, a contrast enema and necropsy was performed for gross and histopathology. Pigs underwent 2 (or 5) days of free intraperitoneal leak prior to device placement and 5 (or 7) subsequent days of endoluminal vacuum therapy. Six of seven early-treated pigs sealed their anastomotic defect, while two of the four treated pigs in this extended group sealed the defect. Endoluminal vacuum therapy is feasible and well tolerated in a pig model, and it has been shown to seal a significant number of freely leaking anastomoses in the early period (86%). This technology warrants further study as it may provide a noninvasive means to treatment of anastomotic leaks.
Analytical Chemistry, 2003
A microchip solid-phase extraction method for purification of DNA from biological samples, such a... more A microchip solid-phase extraction method for purification of DNA from biological samples, such as blood, is demonstrated. Silica beads were packed into glass microchips and the beads immobilized with sol-gel to provide a stable and reproducible solid phase onto which DNA could be adsorbed. Optimization of the DNA loading conditions established a higher DNA recovery at pH 6.1 than 7.6. This lower pH also allowed for the flow rate to be increased, resulting in a decrease in extraction time from 25 min to less than 15 min. Using this procedure, template genomic DNA from human whole blood was purified on the microchip platform with the only sample preparation being mixing of the blood with load buffer prior to loading on the microchip device. Comparison between the microchip SPE (µchipSPE) procedure and a commercial microcentrifuge method showed comparable amounts of PCR-amplifiable DNA could be isolated from cultures of Salmonella typhimurium. The greatest potential of the µchipSPE device was illustrated by purifying DNA from spores from the vaccine strain of Bacillus anthracis, where eventual integration of SPE, PCR, and separation on a single microdevice could potentially enable complete detection of the infectious agent in less than 30 min. 
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Papers by Sanford Feldman