tbuckley/cabot-search huggingface dataset:
ALLERGIC INFLAMMATION
Authors: Henry Z. Movat, Neil V. P. Fernando, Tsuneo Uriuhara, William J. Weiser
Journal: The Journal of Experimental Medicine (1963)

The fine structure of collagen fibrils at sites of antigen-antibody interaction is described. Following injection of antigen (BSA or ferritin) into the center of the cornea of hyperimmune rabbits, an acidophilic ring of precipitate forms at the periphery of the cornea, where antigen and antibody interact in optimal proportions. The precipitate is soon removed by infiltrating polymorphs, but persists longer in leukopenic animals. Electron microscopic examination of the cornea showed no alteration of the collagen fibrils in the area of antigen-antibody precipitation or in the remaining cornea. Contrary to many claims there was no swelling, fragmentation, or disintegration of the fibrils and they had a normal periodicity. Polymorphs infiltrated the precipitates and phagocytosed the antigen-antibody complexes. There was some ultrastructural evidence that degradation of the complexes took place in the polymorphs.
Invariant natural killer T cells regulate anti-tumor immunity by controlling the population of dendritic cells in tumor and draining lymph nodes
Authors: Karsten A Pilones, Joseph Aryankalayil, James S Babb, Sandra Demaria
Journal: Journal for ImmunoTherapy of Cancer (2014)

Invariant natural killer T (iNKT) cells are CD1d-restricted T cells, which respond rapidly to antigen recognition and promote development of anti-tumor immunity in many tumor models. Surprisingly, we previously found that mice deficient in iNKT cells developed spontaneous CD8(+) T cells responses partially effective at inhibiting metastases in mice bearing the 4T1 mammary carcinoma, and showed a markedly improved response to treatment with local radiotherapy and anti-CTLA-4 antibody compared to wild type (WT) mice.To understand the mechanisms of the immunosuppressive function of iNKT cells, dendritic cells (DCs) were analyzed by immunohistochemistry and flow cytometry in WT and iNKT-deficient (iNKT(-/-)) mice. The effects of antibody-mediated blockade of CD1d on DC number and phenotype, priming of anti-tumor T cells, and tumor response to treatment with local radiotherapy and anti-CTLA-4 antibody were evaluated. To determine if the improved response to treatment in the absence of iNKT cells was independent from the immunotherapy employed, 4T1-tumor bearing WT and iNKT(-/-) mice were treated with local radiotherapy in combination with antibody-mediated CD137 co-stimulation.DCs in 4T1 tumors and tumor-draining lymph nodes but not distant lymph nodes were significantly reduced in WT mice compared to iNKT(-/-) mice (p < 0.05), suggesting the selective elimination of DCs cross-presenting tumor-associated antigens by iNKT cells. Consistently, priming of T cells to a tumor-specific CD8 T cell epitope in mice treated with radiotherapy and anti-CTLA-4 or anti-CD137 was markedly enhanced in iNKT(-/-) compared to WT mice. CD1d blockade restored the number of DC in WT mice, improved T cell priming in draining lymph nodes and significantly enhanced response to treatment.Here we describe a novel mechanism of tumor immune escape mediated by iNKT cells that limit priming of anti-tumor T cells by controlling DC in tumors and draining lymph nodes. These results have important implications for the design of immunotherapies targeting iNKT cells.
Impact of a Program to Improve Adherence to Diabetes Guidelines by Primary Care Physicians
Authors: M. Sue Kirkman, Susanna R. Williams, Helena H. Caffrey, David G. Marrero
Journal: Diabetes Care (2002)

OBJECTIVES—Previous studies have shown that primary care physician (PCP) adherence to diabetes guidelines is suboptimal. We sought to determine the state of diabetes care given by independently practicing PCPs in a rural county in Indiana and whether a multifaceted intervention targeting PCPs, patients, and the health care system would improve adherence to diabetes guidelines. RESEARCH DESIGN AND METHODS—Baseline audits to assess adherence to diabetes guidelines were done on charts of the seven PCPs in the county. Audits were repeated after development of local consensus guidelines and feedback of baseline performance and after implementation of various interventions (practice aids, physician detailing, patient education sessions, and implementation of computerized individual meal planning). RESULTS—Before any intervention, rates of adherence to guidelines were low (15% for foot exams, 20% for HbA1c measurement, 23% for eye exam referrals, 33% for urine protein screening, 44% for lipid profiles, 73% for home glucose monitoring, and 78% for blood pressure measurements). One year after development of local consensus guidelines and feedback of baseline performance, significant improvements were seen in blood pressure measurements (71 vs. 83%; P = 0.002), foot exams (19 vs. 42%; P &amp;lt; 0.001), HbA1c measurements (26 vs. 37%; P = 0.012), and PCP eye exams (38 vs. 46%; P = 0.043); a trend toward improvement was seen in referral to eye specialists (25 vs. 33%; P = 0.059). After a second year of multiple interventions, only blood pressure measurements (70 vs. 92%; P &amp;lt; 0.001) and foot exams (22 vs. 47%; P &amp;lt; 0.001) remained significantly improved; all other areas returned to rates indistinguishable from baseline. CONCLUSIONS—In busy primary care practices lacking organizational support and computerized tracking systems, sustained improvements in diabetes care are difficult to attain using traditional physician-targeted approaches.
Urinary Markers of Nucleic Acid Oxidation and Long-Term Mortality of Newly Diagnosed Type 2 Diabetic Patients
Authors: Kasper Broedbaek, Volkert Siersma, Trine Henriksen, Allan Weimann, Morten Petersen, Jon T. Andersen, Espen Jimenez-Solem, Elisabeth S. Stovgaard, Lars J. Hansen, Jan Erik Henriksen, Steen J. Bonnema, Niels de Fine Olivarius, Henrik E. Poulsen
Journal: Diabetes Care (2011)

We analyzed data from a cohort of 1,381 newly diagnosed type 2 diabetic patients to test the hypothesis that urinary markers of nucleic acid oxidation are independent predictors of mortality.We examined the relationship between urinary excretion of markers of DNA oxidation (8-oxo-7,8-dihydro-2'-deoxyguanosine [8-oxodG]) and RNA oxidation (8-oxo-7,8-dihydroguanosine [8-oxoGuo]) and long-term mortality using Cox proportional hazards regression.After multivariate adjustment, the hazard ratios for all-cause and diabetes-related mortality of patients with 8-oxoGuo levels in the highest quartile compared with those in the lowest quartile were 1.44 (1.12-1.85) and 1.54 (1.13-2.10), respectively. Conversely, no significant associations between 8-oxodG and mortality were found in the adjusted analyses.Urinary excretion of the RNA oxidation marker 8-oxoGuo measured shortly after diagnosis of type 2 diabetes predicts long-term mortality independently of conventional risk factors. This finding suggests that 8-oxoGuo could serve as a new clinical biomarker in diabetes.
Neutrophils take the easy way out
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

To migrate out of blood vessels into inflamed tissues, blood cells must cross both the vessel endothelium and basement membrane (BM). According to Wang and colleagues (page 1519), protein-sparse exit sites in the BM pave the way for this cellular escape.






Figure 1

Neutrophils exit veins through protein-sparse regions in the basement membrane (circled).




The signals required for blood cells to adhere to sites of vessel inflammation and to squeeze through endothelial cell (EC) junctions are well defined. But it is unclear how the cells then traverse the tough, underlying network of BM proteins. Migrating cells, such as neutrophils, produce proteases that can cleave BM proteins, which may help the cells drill through the BM.

But Wang and colleagues favor a less destructive model, as drilling holes in the BM could inflict irreversible vessel damage. They now show that steady-state expression of certain (but not all) BM proteins—including laminin 10 and collagen IV—is patchy in small veins, creating discrete areas of low protein expression. Most of these low expression regions were aligned with both EC junctions and gaps between pericytes—structural cells that help synthesize BM proteins. These protein-sparse regions appeared to be the preferred sites for inflammation-induced neutrophil exit.

These data suggest that exiting neutrophils take the path of least resistance, a finding that makes perfect sense to senior author Sussan Nourshargh. “If you have a door, you use it,” says Nourshargh. “You don't blast through the wall.”

How neutrophils find these sites, and whether other cell types use the same exits, is now under investigation.
Genetically related Escherichia coli strains associated with Crohn's disease
Authors: E Masseret
Journal: Gut (2001)

Escherichia coli strains isolated from patients with Crohn's disease (CD) with chronic ileal lesions (n=14), early endoscopic recurrent lesions (n=20), without endoscopic recurrence (n=7), and controls (n=21) were compared by ribotyping. The dendrogram generated by 50 ribotype profile analysis revealed a large cluster of genetically linked E coli strains isolated significantly more frequently from patients with chronic and recurrent CD (24/33 patients) than from controls (9/21) (p<0.05). Most patients operated on for chronic ileal lesions (78.5%) harboured E coli strains belonging to cluster A (p<0.002 v controls). The prevalence of patients with early recurrent lesions harbouring E coli strains belonging to this cluster was high but not significant, although 16 strains isolated from eight patients presented the same ribotype profile. In this cluster, 21 of 26 strains isolated from patients with active CD demonstrated adherent ability to differentiated Caco-2 cells, indicating that most of the genetically related strains share a common virulence trait. Comparison of E coli strains recovered from ulcerated and healthy mucosa of patients operated on for CD demonstrated in each patient that a single strain colonised the intestinal mucosa. Our results suggest that although a single E coli isolate was not found in Crohn's ileal mucosa, some genotypes were more likely than others to be associated with chronic or early recurrent ileal lesions.
Leukemia and Other Cancers After Radiotherapy and Chemotherapy for Hodgkin's Disease&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: J F Boivin, G B Hutchison
Journal: JNCI Journal of the National Cancer Institute (1981)

A cohort study designed to evaluate the carcinogenicity of treatment for Hodgkin's disease (HD) was begun in 1976. This report describes 1,553 patients diagnosed with HD in 1940–75 and presents an analysis of follow-up findings through 1976. Twenty-seven cancers (excluding basal cell and squamous cell carcinomas of skin, trichoepitheliomas, and in situ carcinomas of cervix uteri) were observed 1 year or more after diagnosis of HD, including 6 leukemias. The relative risk (RR) of leukemia in patients treated with intensive chemotherapy with or without radiotherapy relative to general population incidence rates was 140 (95% confidence limits: 50,300). In the subgroup treated with both intensive radiotherapy and intensive chemotherapy, the RR of leukemia was 270 (95% confidence limits: 56,800). No leukemia occurred after treatment with intensive radiotherapy without chemotherapy. For cancers other than leukemia and for non-HD lymphomas, RR were generally not significantly different from the null value one.
Clinical features of several connective tissue diseases with anti-Golgi antibody
Authors: Y YANG
Journal: Annals of the Rheumatic Diseases (2001)

Rodriguez et al were the first to report autoantibodies directed against the Golgi complex identified in the serum of a patient with Sjogren's syndrome (SS).1 Since then, several isolated reports have described the presence of anti-Golgi antibodies (AGAs) in several connective tissue diseases (CTDs).1-7 In addition, immunoblotting and immunoprecipitation studies have suggested that there are at least 14 different Golgi complex autoantigens, and their molecular masses range from 35 to 260 kDa.5 However, few reports describe the association between the clinical features of CTD and AGAs. In this letter we present a case of rheumatoid arthritis (RA) associated with AGAs and review several reported cases.

The patient was a woman born in 1939 who developed seropositive RA in 1990. She was admitted to our hospital in March 1998 because of high grade fever, cough, …
The combined 5-HT2 receptor and calcium channel inhibitor LU49938 restores endothelium dependent responses in the regenerated endothelium of the porcine coronary artery
Authors: S J Park, J J Lee, M Kirchengast, C M Boulanger, P M Vanhoutte
Journal: Cardiovascular Research (1995)

The aim was to evaluate the effect of the combined 5-hydroxytryptamine-2 (5-HT2) receptor antagonist and calcium channel inhibitor LU49938 ((2S)-5-[N-methyl-N-(n-hexyl)] amino-2-isopropyl-2(3.4.5-trimethoxyphenyl)-valeronitrilhydrochloride ) on the endothelium dependent responsiveness of porcine coronary arteries with native and regenerated endothelium.Male Yorkshire pigs were assigned randomly to one of four groups: (1) controls; (2) pigs receiving LU49938 daily (5 mg.kg-1) for four weeks; (3) pigs undergoing balloon de-endothelialisation of the left anterior descending coronary artery; and (4) pigs undergoing balloon de-endothelialisation and receiving LU49938 daily. At four weeks, quantitative coronary angiography, organ chamber experiments, and morphometric studies of the tissues were performed.Treatment with LU49938 did not affect the endothelium dependent responses in native porcine coronary arteries. Intracoronary injection of serotonin caused significantly greater coronary vasoconstriction in group 3 compared with group 4. The cross sectional area of the intima and media of previously de-endothelialised left anterior descending coronary artery increased significantly in group 3, but not in group 4. In arteries with regenerated endothelium, augmented endothelium dependent contractions were noted not only in response to serotonin, but also in response to platelets, noradrenaline, and endothelin-1. The endothelium dependent relaxations to platelets, serotonin, and UK14304 were impaired in the regenerated endothelium, but not those to adenosine diphosphate and SIN-1. However, following four weeks of treatment with LU49938, the pertussis toxin sensitive endothelium dependent responses were restored. The augmented endothelium dependent contraction to endothelin-1 was not altered by the treatment.Chronic treatment with LU49938 restores endothelium dependent, pertussis toxin sensitive, G protein mediated responses in the regenerated endothelium of the porcine coronary artery, and inhibits the intimal thickening following arterial injury.
Effect of Human Anti-DNA Antibodies on Proximal Renal Tubular Epithelial Cell Cytokine Expression
Authors: Susan Yung, Ryan C.W. Tsang, Yuling Sun, Jack K.H. Leung, Tak Mao Chan
Journal: Journal of the American Society of Nephrology (2005)

This study aimed to investigate the effects of human anti-DNA antibodies (Ab) from patients with lupus on renal proximal tubular epithelial cells (PTEC), focusing on alterations in cell morphology and proinflammatory cytokine synthesis. Immunohistochemistry showed increased tubulointerstitial IL-6 expression and IgG deposition in renal biopsies from patients with diffuse proliferative lupus nephritis, not observed in controls or membranous lupus nephritis, which correlated with the severity of inflammatory cell infiltration. Sera from patients with lupus nephritis contained IgG that bound to cultured PTEC. Such binding increased with disease activity and correlated with the level of anti-DNA Ab. Incubation of PTEC with anti-DNA Ab that were isolated during active (active Ab) or inactive (inactive Ab) disease induced IL-6 synthesis, both apically and from the basolateral aspect. This was accompanied by altered cell morphology, increased cell proliferation (P < 0.05), and lactate dehydrogenase release (P < 0.05). The binding of inactive Ab and active Ab to PTEC resulted in differential and sequential upregulation of TNF-alpha, IL-1beta, and IL-6 secretion (P < 0.05). Early induction of TNF-alpha was observed with active Ab; the two then acted synergistically to induce IL-6 secretion. Exposure of PTEC to inactive Ab was associated with modest induction of TNF-alpha, which was not involved in downstream induction of other proinflammatory peptides. These data suggest distinct immunopathogenetic mechanisms during disease flare or remission. Conditioned media from human mesangial cells acted synergistically with anti-DNA Ab to induce cytokine secretion in PTEC. Results from these studies underscore the pivotal role of PTEC in the pathogenesis of tubulointerstitial inflammation and fibrosis in lupus nephritis.
Relationship Between Hospital Performance on a Patient Satisfaction Survey and Surgical Quality
Authors: Greg D. Sacks, Elise H. Lawson, Aaron J. Dawes, Marcia M. Russell, Melinda Maggard-Gibbons, David S. Zingmond, Clifford Y. Ko
Journal: JAMA Surgery (2015)

The Centers for Medicare and Medicaid Services include patient experience as a core component of its Value-Based Purchasing program, which ties financial incentives to hospital performance on a range of quality measures.However, it remains unclear whether patient satisfaction is an accurate marker of high-quality surgical care.OBJECTIVE To determine whether hospital performance on a patient satisfaction survey is associated with objective measures of surgical quality.DESIGN, SETTING, AND PARTICIPANTS Retrospective observational study of participating American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) hospitals.We used data from a linked database of Medicare inpatient claims, ACS NSQIP, the American Hospital Association annual survey, and Hospital Compare from December 2, 2004, through December 31, 2008.A total of 103 866 patients older than 65 years undergoing inpatient surgery were included.Hospitals were grouped by quartile based on their performance on the Hospital Consumer Assessment of Healthcare Providers and Systems survey.Controlling for preoperative risk factors, we created hierarchical logistic regression models to predict the occurrence of adverse postoperative outcomes based on a hospital's patient satisfaction scores.MAIN OUTCOMES AND MEASURES Thirty-day postoperative mortality, major and minor complications, failure to rescue, and hospital readmission. RESULTSOf the 180 hospitals, the overall mean patient satisfaction score was 68.0% (first quartile mean, 58.7%; fourth quartile mean, 76.7%).Compared with patients treated at hospitals in the lowest quartile, those at the highest quartile had significantly lower risk-adjusted odds of death (odds ratio = 0.85; 95% CI, 0.73-0.99),failure to rescue (odds ratio = 0.82; 95% CI, 0.70-0.96),and minor complication (odds ratio = 0.87; 95% CI, 0.75-0.99).This translated to relative risk reductions of 11.1% (P = .04),12.6% (P = .02),and 11.5% (P = .04),respectively.No significant relationship was noted between patient satisfaction and either major complication or hospital readmission.CONCLUSIONS AND RELEVANCE Using a national sample of hospitals, we demonstrated a significant association between patient satisfaction scores and several objective measures of surgical quality.Our findings suggest that payment policies that incentivize better patient experience do not require hospitals to sacrifice performance on other quality measures.
Fibrinopeptide A in plasma of normal subjects and patients with disseminated intravascular coagulation and systemic lupus erythematosus.
Authors: M Cronlund, J Hardin, J Burton, L Lee, E Haber, K J Bloch
Journal: Journal of Clinical Investigation (1976)

A radioimmunoassay for fibrinopeptide A (FPA) has been developed. This assay uses rabbit antibodies induced by injection of native FPA-human serum albumin conjugates and 125I introduced into tyrosine-FPA synthesized in out laboratory. Plasma FPA is separated from fibrinogen by TCA extraction. The assay is capable of detecting as little as 50 pg/ml of FPA. In 20 normal donors this assay revealed a mean concentration of 0.9 ng/ml (0.3 SD). In five patients with disseminated intravascular coagulation, FPA concentrations ranged from 13.0 to 346 ng/ml. Two groups of patients with systemic lupus erythematosus (SLE) whose disease had achieved complete remission were studied; one consisted of four patients with no history of lupus nephritis and another with a history of nephritis. Mean FPA concentrations of 1.5 ng/ml (range, 0.7-1.8 ng/ml) and 2.7 ng/ml (range, 1.1-5.6 ng/ml) were found in these two groups, respectively. Another group of nine patients with active SLE, but without evidence of lupus nephritis, had a mean FPA concentration of 4.5 ng/ml (range, 2.4-7.8 ng/ml). Finally, a group of seven patients with active SLE, including active nephritis, had a mean FPA concentration of 10.2 ng/ml (range, 5.3-17.0 ng/ml). A positive correlation was found between the concentration of plasma FPA and serum DNA-binding activity and an inverse correlation was found between plasma FPA and the concentration of serum C3. No correlation existed between plasma FPA and concentration of serum creatinine. Several possibilities for the origin of plasma FPA in patients with SLE were considered; at present it seems most likely that FPA arises through the action of thrombin on fibrinogen.
Microbiota from Obese Mice Regulate Hematopoietic Stem Cell Differentiation by Altering the Bone Niche
Authors: Yubin Luo, Guang-Liang Chen, Nicole Hannemann, Natacha Ipseiz, Gerhard Krönke, Tobias Bäuerle, Luis Munos, Stefan Wirtz, Georg Schett, Aline Bozec
Journal: Cell Metabolism (2015)
15N-urea metabolism in the functioning human colon: luminal hydrolysis and mucosal permeability.
Authors: B J Moran, A A Jackson
Journal: Gut (1990)

The biopsy channel of the colonoscope was used in a novel approach to the study of in vivo colonic nitrogen metabolism in 12 subjects. A tracer dose of 15N15N-urea was placed in the caecum in six and distal to the splenic flexure in six. The urine and stool were collected for 72 hours and isotopic enrichment was measured in a mass spectrometer. A similar proportion of the dose was recovered in the urine as 15N15N-urea from the right colon, 6%, as was recovered from the left, 4%, showing that the urea was absorbed intact. Urinary 15N14N-urea from the right colon was 18% of the dose compared to 13% from the left colon. This represents urea that has been hydrolysed and absorbed as ammonia. Less than 4% of the dose was recovered in the stool. The greatest proportion of the label, 74% from the right and 82% from the left, could not be accounted for in the urine or the stool and is presumed to have entered the metabolic pool of nitrogen. We conclude that; the colon is permeable to urea, intraluminal hydrolysis occurs and that urea nitrogen enters the metabolic pool of nitrogen in functionally significant quantities.