tbuckley/cabot-search huggingface dataset:
15-Epi-16-(Para-Fluorophenoxy)-Lipoxin A4-Methyl Ester, a Synthetic Analogue of 15-epi-Lipoxin A4, Is Protective in Experimental Ischemic Acute Renal Failure
Authors: Martin O. Leonard, Kieran Hannan, Melissa J. Burne, David W. P. Lappin, Peter Doran, Patrick Coleman, Catherine Stenson, Cormac T. Taylor, Frank Daniels, Catherine Godson, Nicos A. Petasis, Hamid Rabb, Hugh R. Brady
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Lipoxins are endogenous lipoxygenase-derived eicosanoids, generated during inflammatory, hypersensitivity, and vascular events, that display vasodilatory, antiinflammatory, and pro-resolution activity. Here, we evaluated the efficacy of 15-epi-16-(para-fluorophenoxy)-lipoxin A4-methyl ester (15-epi-16-(FPhO)-LXA4-Me), a stable synthetic analogue of aspirin-triggered 15-epi-lipoxin A4 in ischemic acute renal failure (ARF) in NIH Swiss mice. ARF was induced by 30-min crossclamping of renal pedicles and was associated with elevated serum creatinine, morphologic injury, polymorphonuclear leukocyte (PMN) recruitment, and increased mRNA levels for adhesion molecules (intercellular adhesion molecule–1 [ICAM-1] and vascular cell adhesion molecule–1 [VCAM-1]), chemokines (growth regulated oncogene-1 [GRO1]), and cytokines (interleukin–1β [IL-1β] and IL-6) after 24-h reperfusion. A single bolus of 15-epi-16-(FPhO)-LXA4-Me afforded striking functional (mean ± SEM creatinine in mg/dl: sham-operated, 0.77 ± 0.04; ARF + vehicle, 2.49 ± 0.19; ARF + 15-epi-16-(FPhO)-LXA4-Me, 0.75 ± 0.12; P < 0.001) and morphologic protection and reduced PMN infiltration. Treatment with 15-epi-16-(FPhO)-LXA4-Me was also associated with lower IL-1β, IL-6, and GRO1 mRNA levels, whereas ICAM-1 and VCAM-1 mRNA levels were unchanged. Compatible with these results, LXA4 blunted chemoattractant-stimulated PMN migration across HK-2 renal epithelial cell monolayers in vitro, but it did not inhibit cytokine-induced HK-2 ICAM-1 expression or adhesiveness for PMN. Interestingly 15-epi-16-(FPhO)-LXA4-Me–treated animals also displayed increased renal mRNA levels for suppressors of cytokine signaling–1 (SOCS-1) and SOCS-2, but not CIS-1, endogenous inhibitors of cytokine-elicited Jak/Stat-signaling pathways. These results indicate that 15-epi-16-(FPhO)-LXA4-Me is protective in renal ischemia reperfusion injury in vivo, at least partially by modulating cytokine and chemokine expression and PMN recruitment, and provides a rationale for further exploration of the efficacy of LXA4 structural analogues in ischemic ARF and other renal diseases.
Changes in Albuminuria Predict Mortality and Morbidity in Patients with Vascular Disease
Authors: Roland E. Schmieder, Johannes F. E. Mann, Helmut Schumacher, Peggy Gao, Giuseppe Mancia, Michael A. Weber, Matthew McQueen, Teo Koon, Salim Yusuf
Journal: Journal of the American Society of Nephrology (2011)

The degree of albuminuria predicts cardiovascular and renal outcomes, but it is not known whether changes in albuminuria also predict similar outcomes. In two multicenter, multinational, prospective observational studies, a central laboratory measured albuminuria in 23,480 patients with vascular disease or high-risk diabetes. We quantified the association between a greater than or equal to twofold change in albuminuria in spot urine from baseline to 2 years and the incidence of cardiovascular and renal outcomes and all-cause mortality during the subsequent 32 months. A greater than or equal to twofold increase in albuminuria from baseline to 2 years, observed in 28%, associated with nearly 50% higher mortality (HR 1.48; 95% CI 1.32 to 1.66), and a greater than or equal to twofold decrease in albuminuria, observed in 21%, associated with 15% lower mortality (HR 0.85; 95% CI 0.74 to 0.98) compared with those with lesser changes in albuminuria, after adjustment for baseline albuminuria, BP, and other potential confounders. Increases in albuminuria also significantly associated with cardiovascular death, composite cardiovascular outcomes (cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure), and renal outcomes including dialysis or doubling of serum creatinine (adjusted HR 1.40; 95% CI 1.11 to 1.78). In conclusion, in patients with vascular disease, changes in albuminuria predict mortality and cardiovascular and renal outcomes, independent of baseline albuminuria. This suggests that monitoring albuminuria is a useful strategy to help predict cardiovascular risk.
Use of an Oxidized Regenerated Cellulose and Collagen Composite for Healing of Chronic Diabetic Foot Ulcers
Authors: Matteo Monami, Edoardo Mannucci, Masotti Giulio
Journal: Diabetes Care (2002)

Ulcers of lower extremities are often resistant to therapy in diabetic patients. It has recently been reported that the activity of proteases is crucial in wound repair (1), but excessive protease activity can damage granulation tissue, delaying healing. It is noteworthy that protease activity is elevated in fluid from chronic, nonhealing wounds (1).

A recently described protease inactivator matrix (Promogram; Johnson & Johnson, Skipton, U.K.), composed of oxidized regenerated cellulose and collagen, has been shown to reduce elastase, plasmin, and metalloproteinase activity in chronic wound fluids of diabetic patients, stimulating wound repair process (1,2). Both of the components of this matrix, oxidized cellulose (3) and collagen (4), have been reported to accelerate the healing of diabetic …
Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes.
Authors: M Kavallaris, D Y Kuo, C A Burkhart, D L Regl, M D Norris, M Haber, S B Horwitz
Journal: Journal of Clinical Investigation (1997)

The treatment of advanced ovarian cancer with taxol is hindered by the development of drug resistance. The cellular target for taxol is the microtubule that is stabilized by the drug. Taxol preferentially binds to the beta subunit of tubulin of which there are six distinct isotypes in mammalian cells. We have used highly specific oligonucleotides and polymerase chain reaction to analyze expression of all six beta-tubulin genes. Human lung cancer cells (A549) were selected in 12 and 24 nM taxol resulting in cell lines that were 9- and 17-fold resistant, respectively. These cells displayed an altered ratio of classes I, II, III, and IVa beta-tubulin isotypes. Ovarian tumors, seven untreated primary and four taxol- resistant tumor-bearing ascites, displayed significant increases (P < 0.005) in classes I (3.6-fold), III (4.4-fold), and IVa (7.6-fold) isotypes in the taxol-resistant samples as compared with untreated primary ovarian tumors. The increased expression appears to be related to the resistance phenotype, as the basal levels of the class III and IVa isotypes in the untreated tumors were extremely low. This is the first report of altered expression of specific beta-tubulin genes in taxol-resistant ovarian tumors and we propose that the latter may play a role in clinical resistance to taxol.
Disrupted Junctional Membrane Complexes and Hyperactive Ryanodine Receptors After Acute Junctophilin Knockdown in Mice
Authors: Ralph J. van Oort, Alejandro Garbino, Wei Wang, Sayali S. Dixit, Andrew P. Landstrom, Namit Gaur, Angela C. De Almeida, Darlene G. Skapura, Yoram Rudy, Alan R. Burns, Michael J. Ackerman, Xander H.T. Wehrens
Journal: Circulation (2011)

Excitation-contraction coupling in striated muscle requires proper communication of plasmalemmal voltage-activated Ca2+ channels and Ca2+ release channels on sarcoplasmic reticulum within junctional membrane complexes. Although previous studies revealed a loss of junctional membrane complexes and embryonic lethality in germ-line junctophilin-2 (JPH2) knockout mice, it has remained unclear whether JPH2 plays an essential role in junctional membrane complex formation and the Ca(2+)-induced Ca(2+) release process in the heart. Our recent work demonstrated loss-of-function mutations in JPH2 in patients with hypertrophic cardiomyopathy.To elucidate the role of JPH2 in the heart, we developed a novel approach to conditionally reduce JPH2 protein levels using RNA interference. Cardiac-specific JPH2 knockdown resulted in impaired cardiac contractility, which caused heart failure and increased mortality. JPH2 deficiency resulted in loss of excitation-contraction coupling gain, precipitated by a reduction in the number of junctional membrane complexes and increased variability in the plasmalemma-sarcoplasmic reticulum distance.Loss of JPH2 had profound effects on Ca2+ release channel inactivation, suggesting a novel functional role for JPH2 in regulating intracellular Ca2+ release channels in cardiac myocytes. Thus, our novel approach of cardiac-specific short hairpin RNA-mediated knockdown of junctophilin-2 has uncovered a critical role for junctophilin in intracellular Ca2+ release in the heart.
Regulation of Immunoglobulin Light-Chain Recombination by the Transcription Factor IRF-4 and the Attenuation of Interleukin-7 Signaling
Authors: Kristen Johnson, Tamar Hashimshony, Catherine M. Sawai, Jagan M.R. Pongubala, Jane A. Skok, Iannis Aifantis, Harinder Singh
Journal: Immunity (2008)
A CASE OF TUMOUR OF THE SPINAL CORD REMOVED BY OPERATION: A REVIEW OF THE CHIEF DIAGNOSTIC POINTS, VARIETY, AND OPERABILITY OF TUMOURS MET WITH IN THIS REGION
Authors: B. J. Ward
Journal: BMJ (1905)

DIAGNOSIs.EThe diagnosis was Addison'si disease.TREATMENT.After the patient had been-in hospital for three weeks it was decided, after 4some hesitation (owing to the fact that most patients affeotedwith, Addison's disease are very susceptible to cold, and that.theweather at that time in Edinburgh was very cold and incelement), to try the effect of openrair treat- ment; The patient was placed on the balcony outside.the ward.The weather at the time, as has been already stated, was cold and-inclement, wet, windy, stormy, and, sometimes a sharp frost at night.The patient stood the exposure well ; he felt quite comfortable, and did not complain of cold.At the same time, suprarenal extract (5 gr., three times daily) was administered.RESULT oF TREATMENT AND SUBSEQUENT PROGRESS 0P THE CASE.Remarkable Improvement resulted from the open-air treat- ment.The patient gained -at. 6 lb.-in weight; the pigmen- tation of the skin..and the asthenia became markedly less.He was discharged from hospital on 2Ist March, 1904.After hisidischarge he presented himself from time to time as an out-patient, and on each occasion expressed himself as feeling well.-Soon after I last saw him (November 23rd, I904) he returned to work (he was a steward on board a ship) without asking my permission to do so.On Friday, February 24th, 1905, while on board ship returning from the Baltic, he complained of great weakness and inability to do his work.On Saturday, the 25th, he was able to move about and attend to his duties.About 5 p.m. on that day he,aked for whisky, saying I am done for now'; be went to hia bunk *ad lay.-down.On Sunday, the 26th, he appeared to the captain to be unconscious-he did not respond to questions and was unable to take nourishment.The ship arrived sat--Mtrose on Sunday, the 26th, at 5 p.m. Dr.MiddJleton Oonnon, to whom I am indebted for these particu- lars,--.was at once called to see him, but found, at 5.45 p.m., that he was dead.The final attack and death seem to have been,.dueto rapidly developed asthenia and failure of the heart's action, perhaps the result of auto-intoxication-a not uncommon cause of death in Addison's disease.There was, unfortunately, no po8t-mortem examination. REMARKS.*This history is very interesting and very important.It shows that in Addison's disease, even when marked improve- zment takes place, the patient's life, owing to the abolished
Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats.
Authors: A Okuno, H Tamemoto, K Tobe, K Ueki, Y Mori, K Iwamoto, K Umesono, Y Akanuma, T Fujiwara, H Horikoshi, Y Yazaki, T Kadowaki
Journal: Journal of Clinical Investigation (1998)

Troglitazone (CS-045) is one of the thiazolidinediones that activate the peroxisome proliferator-activated receptor gamma (PPARgamma), which is expressed primarily in adipose tissues. To elucidate the mechanism by which troglitazone relieves insulin resistance in vivo, we studied its effects on the white adipose tissues of an obese animal model (obese Zucker rat). Administration of troglitazone for 15 d normalized mild hyperglycemia and marked hyperinsulinemia in these rats. Plasma triglyceride level was decreased by troglitazone in both obese and lean rats. Troglitazone did not change the total weight of white adipose tissues but increased the number of small adipocytes (< 2,500 micron2) approximately fourfold in both retroperitoneal and subcutaneous adipose tissues of obese rats. It also decreased the number of large adipocytes (> 5,000 micron2) by approximately 50%. In fact, the percentage of apoptotic nuclei was approximately 2.5-fold higher in the troglitazone-treated retroperitoneal white adipose tissue than control. Concomitantly, troglitazone normalized the expression levels of TNF-alpha which were elevated by 2- and 1.4-fold in the retroperitoneal and mesenteric white adipose tissues of the obese rats, respectively. Troglitazone also caused a dramatic decrease in the expression levels of leptin, which were increased by 4-10-fold in the white adipose tissues of obese rats. These results suggest that the primary action of troglitazone may be to increase the number of small adipocytes in white adipose tissues, presumably via PPARgamma. The increased number of small adipocytes and the decreased number of large adipocytes in white adipose tissues of troglitazone-treated obese rats appear to be an important mechanism by which increased expression levels of TNF-alpha and higher levels of plasma lipids are normalized, leading to alleviation of insulin resistance.
Malignant Mammary Cells Acquire Independence from Extracellular Context for Regulation of Estrogen Receptor α
Authors: Virginia Novaro, Derek C. Radisky, Nancy E. Ramos Castro, Alessandro Weisz, Mina J. Bissell
Journal: Clinical Cancer Research (2004)

Abstract Interactions between luminal epithelial cells and their surrounding microenvironment govern the normal development and function of the mammary gland. Alterations of these interactions can induce abnormal intracellular signaling pathways that affect the development and progression of breast tumors. One critical component of mammary gland development, as well as breast cancer progression, is the expression of estrogen receptors. In a previous study using cultured nonmalignant mammary epithelial cells, we found that the basement membrane molecules, laminin-1 and collagen-IV, were involved in maintenance of estrogen receptor (ER) α expression, and that this response could be interfered with by disrupting cell-extracellular matrix adhesion. Here we use phenotypically normal mammary epithelial SCp2 cells to dissect the promoter region of the ERα that is involved in the selective response to basement membrane. We also analyze the alteration of this response in SCg6 cells, a malignant cell line that shares a common lineage with the SCp2 cells, to provide insight into the relative overexpression of ERα and the unresponsiveness to basement membrane regulation found in those malignant cells. Evidence is presented to show the relevance of the cross-talk between different signaling pathways in the constitution of a functional tissue organization and how this integration may be disrupted in the malignant phenotype.
Intensive Structured Self-Monitoring of Blood Glucose and Glycemic Control in Noninsulin-Treated Type 2 Diabetes
Authors: Emanuele Bosi, Marina Scavini, Antonio Ceriello, Domenico Cucinotta, Antonio Tiengo, Raffaele Marino, Erminio Bonizzoni, Francesco Giorgino
Journal: Diabetes Care (2013)

We aimed to evaluate the added value of intensive self-monitoring of blood glucose (SMBG), structured in timing and frequency, in noninsulin-treated patients with type 2 diabetes.The 12-month, randomized, clinical trial enrolled 1,024 patients with noninsulin-treated type 2 diabetes (median baseline HbA1c, 7.3% [IQR, 6.9-7.8%]) at 39 diabetes clinics in Italy. After standardized education, 501 patients were randomized to intensive structured monitoring (ISM) with 4-point glycemic profiles (fasting, preprandial, 2-h postprandial, and postabsorptive measurements) performed 3 days/week; 523 patients were randomized to active control (AC) with 4-point glycemic profiles performed at baseline and at 6 and 12 months. Two primary end points were tested in hierarchical order: HbA1c change at 12 months and percentage of patients at risk target for low and high blood glucose index.Intent-to-treat analysis showed greater HbA1c reductions over 12 months in ISM (-0.39%) than in AC patients (-0.27%), with a between-group difference of -0.12% (95% CI, -0.210 to -0.024; P=0.013). In the per-protocol analysis, the between-group difference was -0.21% (-0.331 to -0.089; P=0.0007). More ISM than AC patients achieved clinically meaningful reductions in HbA1c (>0.3, >0.4, or >0.5%) at study end (P<0.025). The proportion of patients reaching/maintaining the risk target at month 12 was similar in ISM (74.6%) and AC (70.1%) patients (P=0.131). At visits 2, 3, and 4, diabetes medications were changed more often in ISM than in AC patients (P<0.001).Use of structured SMBG improves glycemic control and provides guidance in prescribing diabetes medications in patients with relatively well-controlled noninsulin-treated type 2 diabetes.
Effect of Altering Dietary ω-6/ω-3 Fatty Acid Ratios on Prostate Cancer Membrane Composition, Cyclooxygenase-2, and Prostaglandin E2
Authors: Naoko Kobayashi, R. James Barnard, Susanne M. Henning, David Elashoff, Srinivasa T. Reddy, Pinchas Cohen, Pak Leung, Jenny Hong-Gonzalez, Stephen J. Freedland, Jonathan Said, Dorina Gui, Navindra P. Seeram, Laura M. Popoviciu, Dilprit Bagga, David Heber, John A. Glaspy, William J. Aronson
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To determine whether altering the dietary content of ω-6 (n-6) and ω-3 (n-3) polyunsaturated fatty acids affects the growth of androgen-sensitive prostate cancer xenografts, tumor membrane fatty acid composition, and tumor cyclooxygenase-2 and prostaglandin E2 (PGE2) levels. Experimental Design: Individually caged male severe combined immunodeficiency mice were fed isocaloric 20% kcal fat diets with the fat derived either primarily from n-6 fatty acids (n-6 group) or with the fat consisting of n-6 and n-3 fatty acids in a ratio of 1:1 (n-3 group), and injected s.c. with Los Angeles Prostate Cancer 4 (LAPC-4) cells. Tumor volumes and mouse weights were measured weekly, caloric intake was measured 3 days per week, and tumors and serum were harvested at 8 weeks postinjection. Results: Tumor growth rates, final tumor volumes, and serum prostate-specific antigen levels were reduced in the n-3 group relative to the n-6 group. The n-3 group tumors had decreased proliferation (Ki67 staining) and increased apoptosis (terminal nucleotidyl transferase–mediated nick end labeling staining). In vitro proliferation of LAPC-4 cells in medium containing n-3 group serum was reduced by 22% relative to LAPC-4 cells cultured in medium containing serum from the n-6 group. The n-6/n-3 fatty acid ratios in serum and tumor membranes were lower in the n-3 group relative to the n-6 group. In addition, n-3 group tumors had decreased cyclooxygenase-2 protein and mRNA levels, an 83% reduction in PGE2 levels, and decreased vascular endothelial growth factor expression. Conclusion: These results provide a sound basis for clinical trials evaluating the effect of dietary n-3 fatty acids from fish oil on tumor PGE2 and membrane fatty acid composition, and serum and tumor biomarkers of progression in men with prostate cancer.
Development of an internally controlled real-time PCR assay for detection of Chlamydophila psittaci in the LightCycler 2.0 system
Authors: E.R. Heddema, M.G.H.M. Beld, B. de Wever, A.A.J. Langerak, Y. Pannekoek, B. Duim
Journal: Clinical Microbiology and Infection (2006)
Adiponectin and Bariatric Surgery: Associations With Diabetes and Cardiovascular Disease in the Swedish Obese Subjects Study
Authors: Christian Herder, Markku Peltonen, Per-Arne Svensson, Maren Carstensen, Peter Jacobson, Michael Roden, Lars Sjöström, Lena Carlsson
Journal: Diabetes Care (2014)

OBJECTIVE Adiponectin has been implicated in the pathogenesis of type 2 diabetes, but its role for incident diabetes, myocardial infarction, or stroke in obesity is unclear. The aim of this study was to analyze the associations between systemic levels of adiponectin and the aforementioned outcomes in a population with severe obesity at high risk of diabetes and cardiovascular events. RESEARCH DESIGN AND METHODS We measured serum concentrations of total adiponectin in 3,299 participants of the prospective controlled Swedish Obese Subjects (SOS) Study (bariatric surgery group, n = 1,570; control group given usual care, n = 1,729). Median follow-up periods ranged between 10 and 13 years for different outcomes. RESULTS In models containing both baseline adiponectin and 2-year changes in adiponectin, high baseline adiponectin and 2-year increases in adiponectin were associated with decreased risk of diabetes and myocardial infarction among controls. In the surgery group, the 2-year weight loss was paralleled by substantial increase in circulating adiponectin (1,807–1,958 ng/mL per 10-kg weight loss). However, neither baseline adiponectin nor 2-year increases in adiponectin were associated with risk of diabetes or myocardial infarction in the fully adjusted models in the surgery group. No associations were found for stroke in either group. CONCLUSIONS Taken together, baseline adiponectin and 2-year changes were associated with incident diabetes and myocardial infarction in the control group but not in the surgery group. Baseline adiponectin did not predict treatment benefit of bariatric surgery.
Clonal analysis of cytolytic T lymphocyte specificity. I. Phenotypically distinct sets of clones as the cellular basis of cross-reactivity to alloantigens.
Authors: C Taswell, H R MacDonald, J C Cerottini
Journal: The Journal of Experimental Medicine (1980)

The cellular basis of the cytolytic cross-reactivity observed in primary allogeneic (C56BL/6 anti-DBA/2 and C57BL/6 anti-C3H/He) mixed-leukocyte cultures (MLC) was investigated by analysis of the specificity of clonal progeny derived from individual cytolytic T lymphocyte (CTL) precursor cells (CTL-P) contained within these populations. A sensitive mixed-leukocyte microculture (micro-MLC) technique was used with limiting dilution analysis by Poisson statistics to determine the frequency of CTL-P reactive against both specific and third-party (P815 and AKRA) target cells, to calculate the probability that each micro-MLC was a clone derived from a single CTL-P, and to examine the specificity of each micro-MLC assayed separately against both target cells. A total of 287 phenotypically specific, heteroclitic, and cross-reactive micro-MLC from the 2 different strain combinations were observed with a relative frequency of 81, 11, and 8%, respectively, and were calculated to have mean clone probability of 90 and 99% when based, respectively, upon the frequencies of CTL-P reactive against the specific and third-party target cells. These clones were estimated to have an approximate size of 6 X 10(4) cells, which corresponded to roughly 16 cell doublings during the 7 d of culture. 22 clones were successfully subcloned and in virtually every case, the subclones retained the specificity phenotype of the original clone from which they were derived. These results provide direct evidence for three phenotypically distinct sets of CTL as the cellular basis of cross-reactivity in MLC populations assayed against two different target cells.