tbuckley/cabot-search huggingface dataset:
CHRONIC NEPHRITIS WITH AND WITHOUT EDEMA: A STUDY OF CHOLESTEROL IN THESE CONDITIONS
Authors: Francis D. Murphy
Journal: Journal of Clinical Investigation (1927)

Many attempts have been made to correlate the clinical symptoms and pathological changes in the kidney of chronic nephritis, but so far, no general agreement prevails concerning the importance of numerous factors held partially accountable for some of the chief symptoms.This is well illustrated in the case of edema, where many theories have been advanced to explain its presence, and have not been generally accepted, as shown by the extensive review of Loeb (1).Recently, considerable attention has been given to changes in the protein and lipoid content of the blood plasma in renal diseases es- pecially in cases of pure lipoid nephrosis.Numerous studies have appeared dealing with protein changes and their relation to symptoms of nephritis, while comparatively few have dealt with cholesterol and its association with nephritis.This article takes up observations made on a series of cases of chronic nephritis with and without edema and includes a few cases of hypertensive cardiovascular disease with edema from heart failure.The changes in the blood cholesterol, the presence of cholesterol esters in the urine and in the tubular epithelium in those conditions are especially dealt with.To avoid confusion, it should be understood that no cases of pure lipoid nephrosis are included here.The latter condition was studied and reported upon elsewhere (2).Of the thirty-one cases reported here, twenty-five had chronic nephritis and six were cases of hypertensive cardiovascular disease with edema from heart failure.Of the twenty-five patients with chronic nephritis, fourteen were edematous; in eleven no edema ap- peared; seventeen died, and fourteen of these were examined post mortem.Three of the six patients with hypertensive cardiovascular disease died and were examined post mortem.CHOLESTEROL IN CHRONIC NEPHRITIS .
NADPH oxidase-derived superoxide anion mediates angiotensin II-enhanced carotid body chemoreceptor sensitivity in heart failure rabbits
Authors: Y LI, L GAO, I ZUCKER, H SCHULTZ
Journal: Cardiovascular Research (2007)

A previous study from this laboratory showed that elevation of endogenous angiotensin II (Ang II) and upregulation of the angiotensin II type 1 (AT(1)) receptor in the carotid body (CB) are involved in the enhanced peripheral chemoreceptor sensitivity in rabbits with chronic heart failure (CHF). NADPH oxidase-derived superoxide anion mediates the effects of Ang II in many organs. We investigated whether this signaling pathway may mediate the enhanced peripheral chemoreceptor sensitivity induced by Ang II in CHF rabbits.By recording single-unit activity from the carotid sinus nerve in isolated preparations, we found that phenylarsine oxide 2 muM (PAO, NADPH oxidase inhibitor) and TEMPOL 1 mM (superoxide dismutase mimetic) significantly decreased not only the Ang II-enhanced CB chemoreceptor responses to different levels of hypoxia in sham rabbits (Delta-12.5+/-0.8 and Delta-12.8+/-0.9 imp/s at 40.7+/-2.3 mm Hg of PO(2), and Delta-5.6+/-0.5 and Delta-5.3+/-0.4 imp/s at 60.2+/-3.1 mm Hg of PO(2), p<0.05, respectively) but also the CHF-induced elevation of CB chemoreceptor responses to different levels of hypoxia (Delta-13.6+/-1.1 and Delta-13.7+/-0.9 imp/s at 40.9+/-3.1 mm Hg of PO(2), and Delta-6.7+/-1.2 and Delta-6.6+/-0.8 imp/s at 59.8+/-3.5 mm Hg of PO(2), p<0.05). In addition, mRNA and protein expressions of NADPH oxidase components (gp91(phox), p40(phox) and p47(phox)) were higher in the CB from CHF rabbits compared to sham rabbits. Furthermore, 100 pM Ang II induced an increase in superoxide production in CB homogenates from sham rabbits, which was similar to that in CB homogenate from CHF rabbits. PAO and Tempol inhibited the Ang II- and CHF-enhanced superoxide anion production.These results suggest that the enhanced peripheral chemoreceptor sensitivity mediated by Ang II in CHF rabbits occurs via a NADPH oxidase-superoxide signaling pathway.
Complement Gene Expression by Rabbit Heart
Authors: Koji Yasojima, Kenneth S. Kilgore, Ruth A. Washington, Benedict R. Lucchesi, Patrick L. McGeer
Journal: Circulation Research (1998)

Activation of the complement system has been implicated in the pathogenesis of myocardial ischemia/reperfusion injury. It has always been assumed that liver is the primary source of complement components. In the present study, we used the reverse-transcriptase polymerase chain reaction technique to establish that the mRNAs for complement proteins C3 and C9 are expressed in rabbit heart. Rabbit liver, brain, spleen, and kidney were also shown to express C3 and C9 mRNAs. We used Western blotting to establish that these mRNAs in heart are translated into the corresponding proteins. We further established that dramatic upregulation of the mRNAs occurred in Langendorff-perfused isolated hearts subjected to ischemia and reperfusion. C3 mRNA was always expressed at higher levels than was C9 mRNA, but C9 mRNA showed greater upregulation under stress. Compared with levels in control hearts subjected to 5 minutes of normoxic perfusion, hearts subjected to 0.5 hours of ischemia followed by 1 hour of reperfusion had a 4.72-fold increase in C3 mRNA and a 19.5-fold increase in C9 mRNA. By contrast, C3 mRNA in hearts subjected to 3.5 hours of normoxic perfusion showed no change, and those subjected to 3.5 hours of ischemia showed only a 1.72-fold increase, whereas C9 mRNA levels increased by 5.17-fold after 3.5 hours of normoxic perfusion and 12.5-fold after 3.5 hours of ischemia. The results of this study demonstrate for the first time that heart tissue is capable of expressing genes and proteins of the complement system, although it is not yet known which cell types are responsible. They further demonstrate that ischemia and reperfusion of the heart promotes a rapid upregulation of the mRNAs encoding the complement proteins C3 and C9 and that these abnormal levels considerably exceed those of normal liver. These observations are consistent with the hypothesis that local production of complement proteins may contribute significantly to the degree of ischemic injury to the myocardium and that complement expression is augmented by reperfusion.
MAGE-specific T cells detected directly ex-vivo correlate with complete remission in metastatic breast cancer patients after sequential immune-endocrine therapy
Authors: Maxwell Janosky, Rachel L Sabado, Crystal Cruz, Isabelita Vengco, Farah Hasan, Arthur Winer, Linda Moy, Sylvia Adams
Journal: Journal for ImmunoTherapy of Cancer (2014)

Studies suggest that conventional cancer therapies given after immunotherapy (IT) can boost antitumor immunity and possibly improve response rates and progression-free survival. We report two cases of metastatic breast cancer with durable complete responses (CRs) after sequential IT and endocrine therapy. Immune analyses of these long-term disease-free breast cancer patients previously treated with imiquimod (IMQ) suggest in-situ vaccination is achieved by topical application of the TLR-7 agonist directly onto tumors. Furthermore, IT-induced antigen-specific T cells were expanded by subsequent endocrine therapy and correlated with response, persisting > 2 years. Our findings therefore suggest that the induction/boosting of polyfunctional tumor antigen-specific T in response to sequential immune endocrine therapy and detected directly ex-vivo can serve as a peripheral blood biomarker for true clinical benefit.
Compartmentalization of cAMP-Dependent Signaling by Phosphodiesterase-4D Is Involved in the Regulation of Vasopressin-Mediated Water Reabsorption in Renal Principal Cells
Authors: Eduard Stefan, Burkhard Wiesner, George S. Baillie, Rustam Mollajew, Volker Henn, Dorothea Lorenz, Jens Furkert, Katja Santamaria, Pavel Nedvetsky, Christian Hundsrucker, Michael Beyermann, Eberhard Krause, Peter Pohl, Irene Gall, Andrew N. MacIntyre, Sebastian Bachmann, Miles D. Houslay, Walter Rosenthal, Enno Klussmann
Journal: Journal of the American Society of Nephrology (2006)

The cAMP/protein kinase A (PKA)-dependent insertion of water channel aquaporin-2 (AQP2)-bearing vesicles into the plasma membrane in renal collecting duct principal cells (AQP2 shuttle) constitutes the molecular basis of arginine vasopressin (AVP)-regulated water reabsorption. cAMP/PKA signaling systems are compartmentalized by A kinase anchoring proteins (AKAP) that tether PKA to subcellular sites and by phosphodiesterases (PDE) that terminate PKA signaling through hydrolysis of localized cAMP. In primary cultured principal cells, AVP causes focal activation of PKA. PKA and cAMP-specific phosphodiesterase-4D (PDE4D) are located on AQP2-bearing vesicles. The selective PDE4 inhibitor rolipram increases AKAP-tethered PKA activity on AQP2-bearing vesicles and enhances the AQP2 shuttle and thereby the osmotic water permeability. AKAP18delta, which is located on AQP2-bearing vesicles, directly interacts with PDE4D and PKA. In response to AVP, PDE4D and AQP2 translocate to the plasma membrane. Here PDE4D is activated through PKA phosphorylation and reduces the osmotic water permeability. Taken together, a novel, compartmentalized, and physiologically relevant cAMP-dependent signal transduction module on AQP2-bearing vesicles, comprising anchored PDE4D, AKAP18delta, and PKA, has been identified.
Prostate Cancer and the Will Rogers Phenomenon
Authors: Peter C. Albertsen, James A. Hanley, George H. Barrows, David F. Penson, Pam D. H. Kowalczyk, M. Melinda Sanders, Judith Fine
Journal: JNCI Journal of the National Cancer Institute (2005)

Information on tumor stage and grade are used to assess cancer prognosis and to produce standardized comparisons of end results over time. Changes in the interpretation of classification schemes can alter the apparent distribution of cancer stage or grade in the absence of a true biologic change. Since the introduction of prostate-specific antigen testing, the reported incidence of low-grade prostate cancer has declined. To determine whether this decline is in part a result of Gleason score reclassification during the same time period, we documented the potential impact of reclassification between 1992 and 2002 on clinical outcomes.A population-based cohort of 1858 men who were < or = 75 years of age at diagnosis of prostate cancer in 1990-1992 was assembled retrospectively from the Connecticut Tumor Registry. Histology slides of the diagnostic prostate tissue were retrieved and reread in 2002-2004 by an experienced pathologist blinded to the original Gleason score readings. Prostate cancer mortality rates for the cohort calculated using the original Gleason score readings were compared with those calculated using the contemporary Gleason score readings. Statistical tests were two sided.The contemporary Gleason score readings were statistically significantly higher than the original readings (mean score increased from 5.95 to 6.8; difference = 0.85, 95% confidence interval = 0.79 to 0.91; P < .001). Consequently, the Gleason score-standardized contemporary prostate cancer mortality rate (1.50 deaths per 100 person-years) appeared to be 28% lower than standardized historical rates (2.08 deaths per 100 person-years), even though the overall outcome was unchanged. This apparent improvement in mortality held for all Gleason score categories.In this population, a decline in the reported incidence of low-grade prostate cancers appears to be the result of Gleason score reclassification over the past decade. This reclassification resulted in apparent improvement in clinical outcomes. This finding reflects a statistical artifact known as the Will Rogers phenomenon.
Cardiac Myocyte-Derived Follistatin-Like 1 Prevents Renal Injury in a Subtotal Nephrectomy Model
Authors: Satoko Hayakawa, Koji Ohashi, Rei Shibata, Yoshiyuki Kataoka, Megumi Miyabe, Takashi Enomoto, Yusuke Joki, Yuuki Shimizu, Takahiro Kambara, Yusuke Uemura, Daisuke Yuasa, Hayato Ogawa, Kazuhiro Matsuo, Mizuho Hiramatsu-Ito, Maurice J.B. van den Hoff, Kenneth Walsh, Toyoaki Murohara, Noriyuki Ouchi
Journal: Journal of the American Society of Nephrology (2014)

Heart disease contributes to the progression of CKD. Heart tissue produces a number of secreted proteins, also known as cardiokines, which participate in intercellular and intertissue communication. We recently reported that follistatin-like 1 (Fstl1) functions as a cardiokine with cardioprotective properties. Here, we investigated the role of cardiac Fstl1 in renal injury after subtotal nephrectomy. Cardiac-specific Fstl1-deficient (cFstl1-KO) mice and wild-type mice were subjected to subtotal (5/6) nephrectomy. cFstl1-KO mice showed exacerbation of urinary albumin excretion, glomerular hypertrophy, and tubulointerstitial fibrosis after subtotal renal ablation compared with wild-type mice. cFstl1-KO mice also exhibited increased mRNA levels of proinflammatory cytokines, including TNF-α and IL-6, NADPH oxidase components, and fibrotic mediators, in the remnant kidney. Conversely, systemic administration of adenoviral vectors expressing Fstl1 (Ad-Fstl1) to wild-type mice with subtotal nephrectomy led to amelioration of albuminuria, glomerular hypertrophy, and tubulointerstitial fibrosis, accompanied by reduced expression of proinflammatory mediators, NADPH oxidase components, and fibrotic markers in the remnant kidney. In cultured human mesangial cells, treatment with recombinant FSTL1 attenuated TNF-α-stimulated expression of proinflammatory cytokines. Treatment of mesangial cells with FSTL1 augmented the phosphorylation of AMP-activated protein kinase (AMPK), and inhibition of AMPK activation abrogated the anti-inflammatory effects of FSTL1. These data suggest that Fstl1 functions in cardiorenal communication and that the lack of Fstl1 production by myocytes promotes glomerular and tubulointerstitial damage in the kidney.
Comorbid Conditions in Kidney Transplantation
Authors: Christine Wu, Idris Evans, Raymond Joseph, Ron Shapiro, Henkie Tan, Amit Basu, Cynthia Smetanka, Ahktar Khan, Jerry McCauley, Mark Unruh
Journal: Journal of the American Society of Nephrology (2005)

Although the impact of comorbidity on outcomes in ESRD has been evaluated extensively, its contribution after kidney transplantation has not been well studied. It is believed that comorbidity assessment is critical to the informed interpretation of kidney transplant outcomes. In this study, the Charlson Comorbidity Index was used to assess the comorbid conditions of 715 patients who underwent kidney transplantation at the Starzl Transplant Institute between January 1998 and January 2003. The impact of pretransplantation comorbidity on the development of acute cellular rejection after transplantation and on patient and graft survival was examined. The most common comorbid conditions among our patient population were diabetes (<i>n</i> = 217, 30.3%) and heart failure (<i>n</i> = 85, 11.9%). It was found the number of patients with high comorbidity at the Starzl Transplant Institute has increased significantly over time (<i>P</i> = 0.04). In multivariate adjusted models, high comorbidity was associated with an increased risk for patient death, both in the perioperative period (hazard ratio 3.20, 95% confidence interval 1.32 to 7.78; <i>P</i> = 0.01) and &gt;3 mo after transplantation (hazard ratio 2.63; 95% confidence interval 1.62 to 4.28; <i>P</i> &lt; 0.001). The Charlson Comorbidity Index is a practical tool for the evaluation of comorbidity in the transplant population, which has an increasing burden of comorbid disease. Increased comorbidity affects both perioperative and long-term patient outcomes and carries significant implications not only for the development of individual patient therapeutic strategies but also for the interpretation of patient trials and the development of policies that govern distribution of donor organs.
Lethal hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type II
Authors: Anselm Enders, Barbara Zieger, Klaus Schwarz, Ayami Yoshimi, Carsten Speckmann, Eva-Maria Knoepfle, Udo Kontny, Christoph Müller, Alan Nurden, Jan Rohr, Matthias Henschen, Ulrich Pannicke, Charlotte Niemeyer, Paquita Nurden, Stephan Ehl
Journal: Blood (2006)
Pathophysiological consequences of atherosclerosis extend into the coronary microcirculation. Restoration of endothelium-dependent responses by L-arginine.
Authors: L Kuo, M J Davis, M S Cannon, W M Chilian
Journal: Circulation Research (1992)

The goals of this study were 1) to quantitate the effects of atherosclerosis on physiological and pharmacological endothelium-dependent vasoactive responses in coronary arterioles downstream from arterial lesions and 2) to determine if administration of L-arginine, the precursor for endothelium-derived was induced in pigs, and vasomotor responses of isolated, cannulated coronary arterioles (30-70 microns in diameter) were assessed by measuring diameter changes in vitro. To assess pharmacological alterations of endothelium-dependent responses, dose-response curves were constructed to ADP, serotonin, and histamine. To assess physiological alterations in endothelial function, different flow rates were established across the vessel. Arteriolar diameters were measured in vessels from normal and atherosclerotic pigs under control conditions, after administration of L-arginine, and after endothelial denudation. In arterioles from normal pigs, administration of serotonin, histamine, or ADP produced dose-dependent vasodilation, which was abolished by endothelial denudation. In arterioles from atherosclerotic pigs, administration of histamine, serotonin, and ADP produced dilation at only the highest doses (10(-6)-10(-7) M), and the extent of dilation was only 20-30% of that observed in arterioles from normal pigs. Initiation of flow also produced vasodilation in arterioles from normal pigs that was completely abolished after endothelial denudation. In arterioles from atherosclerotic pigs, flow-induced responses were absent. These abnormal physiological and pharmacological responses (i.e., blunted vasodilation to pharmacological stimulation and to flow) were restored after administration of L-arginine for 40 minutes. The vascular responses after administration of L-arginine were not different from those observed under control conditions in arterioles from normal pigs. In addition, L-arginine did not restore vasodilation to the endothelium-dependent agonists in denuded segments. From these data in arterioles downstream from atherosclerotic lesions, we conclude that 1) the ED50 and maximal responses of endothelium-dependent vasodilation to ADP, histamine, and serotonin are attenuated; 2) the physiological response to flow, that is, flow-mediated endothelium-dependent vasodilation, is absent; and 3) the abnormality in arteriolar responsiveness during large vessel disease involves an impairment of the synthesis and/or release of endothelium-derived relaxing factor.
Mortality in Older Men With Low-Risk Prostate Cancer and High Comorbidity
Authors: Pär Stattin
Journal: Journal of Clinical Oncology (2015)

Journal of ClinicalOncology, Prasad et al 1 conclude that there is a need to "ameliorate the decreased survival following a prostate cancer diagnosis in the depressed male patient," based on the claim that their study shows that "preexisting diagnosis of depressive disorder is independently associated with treatment choice and outcomes of localized prostate can-cer."Few physicians would object to this conclusion; however, there are absolutely no results in the report by Prasad et al in support of this claim, because no data on death resulting from prostate cancer are presented.In their study, Prasad et al 1 make use of SEER data, and they investigate all-cause mortality in men age Ͼ 67 years diagnosed with prostate cancer from 2004 to 2007 and observed until end of 2009 (ie, maximum of 5-year follow-up).Many men with depression were age Ͼ 75 years (48%), and 24% had a Charlson comorbidity index Ն 2.In terms of National Comprehensive Cancer Network risk category, there were 10,860 men (28%) with low-risk cancer, 17,105
Tumor-promoting phorbol esters selectively abrogate the expression of the T4 differentiation antigen expressed on normal and malignant (Sézary) T helper lymphocytes.
Authors: W Solbach
Journal: The Journal of Experimental Medicine (1982)

12-O-tetradecanoylphorbol-13-acetate (TPA) selectively abrogates, in nanomolar concentrations, the expression of the T4 differentiation antigen, as defined by the monoclonal anti-T4 antibody (1) on Il-2-producing T helper lymphocytes from normal donors and on T helper lymphocytes from a patient with malignant T cell lymphoma (Sézary's syndrome); this compound does not affect the expression of cell surface antigens as defined by the antibodies anti-OKT3, -T6, -T8, -T11, Ia, or anti-surface immunoglobulin. Abrogation of the T4 antigen expression is concentration dependent, completed within 8 h of incubation at 37 degrees C, does not occur at 4 degrees C, and is reversible. Only those phorbol-esters known to have tumor-promoting activity in vivo (2) affect the T4 antigen, whereas nonpromoting compounds are ineffective.
Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases
Authors: Dietger Niederwieser, Michael Maris, Judith A. Shizuru, Effie Petersdorf, Ute Hegenbart, Brenda M. Sandmaier, David G. Maloney, Barry Storer, Thoralf Lange, Thomas Chauncey, Michael Deininger, Wolfram Pönisch, Claudio Anasetti, Ann Woolfrey, Marie-Terese Little, Karl G. Blume, Peter A. McSweeney, Rainer F. Storb
Journal: Blood (2003)
Reversal of insulin resistance in type I diabetes after treatment with continuous subcutaneous insulin infusion.
Authors: I Lager, P Lonnroth, H von Schenck, U Smith
Journal: BMJ (1983)

Insulin responsiveness was studied with the euglycaemic glucose clamp technique in seven patients with type I diabetes and in six control subjects matched for age and weight. The glucose disposal rate was significantly reduced in the diabetic subjects when they were receiving conventional insulin treatment compared with the control group, showing insulin resistance in the diabetics. The diabetic patients were again studied after eight days of intensified metabolic control achieved with continuous subcutaneous insulin infusion. During the infusion a more physiological insulin regimen was used compared with their regular treatment, less of the total insulin dose being given as continuous infusion and more as bolus doses before meals. The insulin resistance in the diabetics was largely reversed after this improved metabolic control. Dose response studies showed an increased glucose disposal rate at all plasma insulin concentrations, including the maximum insulin concentration, indicating a predominant effect of the continuous infusion regimen at the postreceptor level. The improved insulin effect seen with continuous subcutaneous insulin infusion could be due to the improved metabolic control achieved as well as the more physiological regimen.