tbuckley/cabot-search huggingface dataset:
IMMUNITY IN MUMPS
Authors: John F. Enders, Sidney Cohen, Lewis W. Kane
Journal: The Journal of Experimental Medicine (1945)

1. A specific antibody, demonstrable by the technique of complement fixation, regularly appears, or increases in concentration, in the sera of human beings during an attack of mumps or during convalescence. 2. Specific dermal hypersensitivity, demonstrable by the injection of heat-inactivated mumps virus, has been shown to develop in 6 human beings after recovery from mumps. 3. Complement-fixing antibody and the hypersensitive state also emerge as a result of clinically inapparent infection with the virus of mumps. 4. These two phenomena are apparently unrelated in respect to immunologic mechanisms. 5. The data presented indicate that the complement fixation test should prove of value both in diagnosis and in the determination of immunity. 6. The skin test for dermal hypersensitivity, on the other hand, becomes positive after recovery and therefore would appear to be useful only as an index of resistance.
Delayed Graft Function and Cast Nephropathy Associated with Tacrolimus Plus Rapamycin Use
Authors: Kelly D. Smith, Lucile E. Wrenshall, Roberto F. Nicosia, Raimund Pichler, Christopher L. Marsh, Charles E. Alpers, Nayak Polissar, Connie L. Davis
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Delayed graft function (DGF) occurs in 15 to 25% (range, 10 to 62%) of cadaveric kidney transplant recipients and up to 9% of living donor recipients. In addition to donor, recipient, and procedural factors, the choice of immunosuppression may influence the development of DGF. The impact of immunosuppression on DGF was studied. The frequency of DGF was evaluated in first cadaveric or living donor kidney allograft recipients (n = 144) transplanted at the University of Washington from November 1999 through September 1, 2001. Donor, recipient, and procedural factors, as well as biopsy results, were compared between patients who developed DGF and those who did not. DGF was more common in patients treated with rapamycin than without (25% versus 8.9%, P = 0.02) and positively correlated with rapamycin dose (P = 0.008). In those developing DGF, the duration of posttransplant dialysis increased with donor age (P = 0.003) but decreased with mycophenolate mofetil use (P = 0.01). All biopsies during episodes of DGF demonstrated changes of acute tubular injury. Of the patients with tubular injury, 12 treated with rapamycin and tacrolimus developed intratubular cast formation indistinguishable from myeloma cast nephropathy. Histologic, immunohistochemical, and ultrastructural studies indicated that these casts were composed at least in part of degenerating renal tubular epithelial cells. These findings suggest that rapamycin therapy exerts increased toxicity on tubular epithelial cells and/or retards healing, leading to an increased incidence of DGF. Additionally, rapamycin treatment combined with a calcineurin inhibitor may lead to extensive tubular cell injury and death and a unique form of cast nephropathy. E-mail: [email protected]
Perceptions and experiences of taking oral hypoglycaemic agents among people of Pakistani and Indian origin: qualitative study
Authors: Julia Lawton, Naureen Ahmad, Nina Hallowell, Lisa Hanna, Margaret Douglas
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To explore British Pakistani and British Indian patients9 perceptions and experiences of taking oral hypoglycaemic agents (OHAs). <b>Design</b> Observational cross sectional study using in-depth interviews in English or Punjabi. <b>Setting and participants</b> 32 patients of Pakistani and Indian origin with type 2 diabetes, recruited from primary care and community sources in Edinburgh, Scotland. <b>Results</b> Respondents reported complex and ambivalent views about OHAs, which reflected their ambivalent attitudes towards Western drugs in general. Respondents considered OHAs to be an important part of the diabetic regimen because they perceived British healthcare professionals to be competent and trustworthy prescribers, and they considered the medicines available in Britain to be superior to those on the Indian subcontinent. Despite this, some respondents made deliberate efforts to reduce their tablet intake without being advised to do so. Reasons for this included perceptions that drugs worked by providing relief of symptoms and concerns that OHAs could be detrimental to health if taken for long periods, in conjunction with other drugs, or without traditional foods. <b>Conclusions</b> British Pakistani and Indian patients9 perceptions of their OHAs may partly derive from popular ideas about drugs on the Indian subcontinent. Cultural factors need to be understood and taken into consideration to ensure that these patients are given appropriate advice and to avoid unnecessary changes to prescriptions.
Early structural changes in cartilage and bone are required for the attachment and invasion of inflamed synovial tissue during destructive inflammatory arthritis
Authors: Adelheid Korb-Pap, Athanasios Stratis, Katja Mühlenberg, Birgit Niederreiter, Silvia Hayer, Frank Echtermeyer, Richard Stange, Jochen Zwerina, Thomas Pap, Hermann Pavenstädt, Georg Schett, Josef S Smolen, Kurt Redlich
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To elucidate the mechanisms involved in cartilage damage in an experimental model of rheumatoid arthritis (RA) by specifically addressing the time course of extracellular matrix degradation and the contribution of cell–matrix interactions for initiation and perpetuation of this process. <h3>Methods</h3> The human tumour necrosis factor (TNF) transgenic (hTNFtg) mouse model of RA was used to analyse the time course of pannus attachment to the cartilage and cartilage destruction, respectively, and crossed hTNFtg mice with interleukin (IL)-1<sup>−/−</sup> animals were used to investigate the role of IL-1 on these TNF-induced mechanisms in vivo. In addition, an in vitro attachment assay using synovial fibroblasts (SFs) from hTNFtg mice and freshly isolated articular cartilage was used to determine the role of proteoglycan loss in attachment of SFs and the role of the transmembrane heparan sulfate proteoglycan syndecan-4. <h3>Results</h3> In vivo analyses of hTNFtg mice showed that proteoglycan loss induced by IL-1 precedes and constitutes an important prerequisite for these processes as, in hTNFtg mice, IL-1 deficiency protected from the loss of cartilage proteoglycans and almost completely prevented the attachment and subsequent invasion of inflamed synovial tissue into cartilage. In vitro studies confirmed that loss of cartilage proteoglycans is required for attachment of SFs and that syndecan-4 is prominently involved in SF attachment and activation. <h3>Conclusions</h3> The results of this study suggest that the loss of cartilage proteoglycans is an early event in the course of destructive arthritis that facilitates the attachment of the inflamed synovial membrane and also initiates matrix degradation and inflammation through cell–matrix interactions.
Aquaporin-1 water channel expression in human kidney.
Authors: A B Maunsbach, D Marples, E Chin, G Ning, C Bondy, P Agre, S Nielsen
Journal: Journal of the American Society of Nephrology (1997)

The pattern of aquaporin-1 water channel protein (AQP1) expression in the human kidney was analyzed by immunocytochemistry using semi-thin and optimized high-resolution immunoelectron microscopy based on freeze-substituted and Lowicryl HM20 embedded tissue. In addition, in situ hybridization was used to determine AQP1 mRNA distribution. Immunoblots revealed a 28-kd band and a 35- to 45-kd band corresponding to unglycosylated and glycosylated AQP1. Glomerular capillary endothelium exhibited extensive AQP1 labeling, whereas glomerular podocytes and Bowman's capsule epithelium were unlabeled. AQP1 was localized in the proximal tubule, including the neck region directly connected to the glomerulus. However, there was a marked difference in the level of expression between cross-sections of the convoluted part and the proximal straight tubules, the latter displaying the most intense labeling. AQP1 labeling continued uninterrupted from the proximal straight tubule into descending thin limbs in outer medulla. Abrupt transitions from heavily labeled to unlabeled segments of thin limbs were observed, primarily in the inner medulla. This may represent the transition from the water-permeable thin descending limb to the water-impermeable thin ascending limb. In addition, heavy labeling of fenestrated endothelium was also observed in peritubular capillaries in cortex, outer medulla, and inner medulla. Immunolabeling controls were negative. In situ hybridization documented a marked difference in AQP1 mRNA levels within the proximal tubule, with the greatest AQP1 mRNA expression in straight proximal tubules. Glomeruli also showed marked signals, and descending thin limbs exhibited extensive expression in exact concordance with the immunocytochemical results. It was concluded that: (1) AQP1 is present in all proximal tubule segments, including segment 1 and the neck region, but there is a pronounced difference in expression levels with respect to both protein and mRNA levels; (2) AQP1 labeling is observed in the endothelium of fenestrated peritubular capillaries, as well as fenestrated glomerular capillaries; (3) AQP1 labeling continues directly from proximal tubules to descending thin limbs; and (4) abrupt transitions from labeled to unlabeled thin limb epithelium are noted.
Inhalation of Nitric Oxide Prevents Ischemic Brain Damage in Experimental Stroke by Selective Dilatation of Collateral Arterioles
Authors: Nicole A. Terpolilli, Seong-Woong Kim, Serge C. Thal, Hiroharu Kataoka, Vilia Zeisig, Bjoern Nitzsche, Benjamin Klaesner, Changlian Zhu, Susanne Schwarzmaier, Lilja Meissner, Uta Mamrak, Doortje C. Engel, Alexander Drzezga, Rakesh P. Patel, Klas Blomgren, Henryk Barthel, Johannes Boltze, Wolfgang M. Kuebler, Nikolaus Plesnila
Journal: Circulation Research (2011)

Rationale: Stroke is the third most common cause of death in industrialized countries. The main therapeutic target is the ischemic penumbra, potentially salvageable brain tissue that dies within the first few hours after blood flow cessation. Hence, strategies to keep the penumbra alive until reperfusion occurs are needed. Objective: To study the effect of inhaled nitric oxide on cerebral vessels and cerebral perfusion under physiological conditions and in different models of cerebral ischemia. Methods and Results: This experimental study demonstrates that inhaled nitric oxide (applied in 30% oxygen/70% air mixture) leads to the formation of nitric oxide carriers in blood that distribute throughout the body. This was ascertained by in vivo microscopy in adult mice. Although under normal conditions inhaled nitric oxide does not affect cerebral blood flow, after experimental cerebral ischemia induced by transient middle cerebral artery occlusion it selectively dilates arterioles in the ischemic penumbra, thereby increasing collateral blood flow and significantly reducing ischemic brain damage. This translates into significantly improved neurological outcome. These findings were validated in independent laboratories using two different mouse models of cerebral ischemia and in a clinically relevant large animal model of stroke. Conclusions: Inhaled nitric oxide thus may provide a completely novel strategy to improve penumbral blood flow and neuronal survival in stroke or other ischemic conditions.
Lineage of Bone Marrow–Derived Cells in Atherosclerosis
Authors: Hiroshi Iwata, Ichiro Manabe, Ryozo Nagai
Journal: Circulation Research (2013)

Atherosclerosis is a chronic inflammatory disease driven by lipids and other atherogenic factors. It is characterized by a dynamic and complex pathological process of bone marrow–derived cells playing divergent roles. Recent studies have begun unraveling the contribution of growing varieties of subsets of immune cells and other bone marrow–derived cells to atherogenesis. For example, bone marrow–derived vascular progenitor cells have been shown to play an important role in the pathogenesis of atherosclerosis. This review provides an overview of the current understanding of contributions of bone marrow–derived cells to atherosclerosis. Particular focus is placed on myeloid cells and vascular progenitor cells. We also summarize the uncertainty surrounding cellular lineage identity and functions. Expansion of our understanding of pathological roles of various subsets of bone marrow–derived cells in atherosclerosis may lead to identification of novel cellular and molecular targets for development of therapeutic strategies.
Rivaroxaban in Patients with a Recent Acute Coronary Syndrome
Authors: Jessica L. Mega, Eugene Braunwald, Stephen D. Wiviott, Jean-Pierre Bassand, Deepak L. Bhatt, Christoph Bode, Paul Burton, Marc Cohen, Nancy Cook-Bruns, Keith A.A. Fox, Shinya Goto, Sabina A. Murphy, Alexei N. Plotnikov, David Schneider, Xiang Sun, Freek W.A. Verheugt, C. Michael Gibson
Journal: New England Journal of Medicine (2011)

Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis. Since factor Xa plays a central role in thrombosis, the inhibition of factor Xa with low-dose rivaroxaban might improve cardiovascular outcomes in patients with a recent acute coronary syndrome.In this double-blind, placebo-controlled trial, we randomly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months. The primary efficacy end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke.Rivaroxaban significantly reduced the primary efficacy end point, as compared with placebo, with respective rates of 8.9% and 10.7% (hazard ratio in the rivaroxaban group, 0.84; 95% confidence interval [CI], 0.74 to 0.96; P=0.008), with significant improvement for both the twice-daily 2.5-mg dose (9.1% vs. 10.7%, P=0.02) and the twice-daily 5-mg dose (8.8% vs. 10.7%, P=0.03). The twice-daily 2.5-mg dose of rivaroxaban reduced the rates of death from cardiovascular causes (2.7% vs. 4.1%, P=0.002) and from any cause (2.9% vs. 4.5%, P=0.002), a survival benefit that was not seen with the twice-daily 5-mg dose. As compared with placebo, rivaroxaban increased the rates of major bleeding not related to coronary-artery bypass grafting (2.1% vs. 0.6%, P<0.001) and intracranial hemorrhage (0.6% vs. 0.2%, P=0.009), without a significant increase in fatal bleeding (0.3% vs. 0.2%, P=0.66) or other adverse events. The twice-daily 2.5-mg dose resulted in fewer fatal bleeding events than the twice-daily 5-mg dose (0.1% vs. 0.4%, P=0.04).In patients with a recent acute coronary syndrome, rivaroxaban reduced the risk of the composite end point of death from cardiovascular causes, myocardial infarction, or stroke. Rivaroxaban increased the risk of major bleeding and intracranial hemorrhage but not the risk of fatal bleeding. (Funded by Johnson & Johnson and Bayer Healthcare; ATLAS ACS 2-TIMI 51 ClinicalTrials.gov number, NCT00809965.).
Functional Imaging Using Diffuse Optical Spectroscopy of Neoadjuvant Chemotherapy Response in Women with Locally Advanced Breast Cancer
Authors: Hany Soliman, Anoma Gunasekara, Mary Rycroft, Judit Zubovits, Rebecca Dent, Jacqueline Spayne, Martin J. Yaffe, Gregory J. Czarnota
Journal: Clinical Cancer Research (2010)

Functional imaging with tomographic near-infrared diffuse optical spectroscopy (DOS) can measure tissue concentration of deoxyhemoglobin (Hb), oxyhemoglobin (HbO2), percent water (%water), and scattering power (SP). In this study, we evaluated tumor DOS parameters and described their relationship to clinical and pathologic outcome in patients undergoing neoadjuvant therapy for locally advanced breast cancer.Ten patients were enrolled and intended to undergo five scans each. Scans were taken up to 3 days before treatment and at 1, 4, and 8 weeks after neoadjuvant treatment before surgery. Changes in volume of interest weighted tissue Hb, HbO2, %water, and SP corresponding to the tumor were compared with clinical and pathologic response.All patients' tumor volumes of interest were significantly different compared with background tissue for all parameters. Five patients had a good pathologic response. Four patients were considered nonresponders. One patient initially did not respond to chemotherapy but, after a change in chemotherapy, had a good response. In the five patients with a good response, the mean drop in Hb, HbO2, %water, and SP from baseline to the 4-week scan was 67.6% (SD = 20.8), 58.9% (SD = 20.3), 51.2% (SD = 28.3), and 52.6% (SD = 26.4), respectively. In contrast, the four nonresponders had a mean drop of 17.7% (SD = 9.8), 18.0% (SD = 20.8), 15.4% (SD = 11.7), and 12.6% (SD = 10.2) for Hb, HbO2, %water, and SP, respectively.Responders and nonresponders were significantly different for all functional parameters at the 4-week scan, except for %water, which approached significance. Thus, DOS could be used as an early detector of tumor response.
Preclinical studies of Apogossypolone: a new nonpeptidic pan small-molecule inhibitor of Bcl-2, Bcl-XL and Mcl-1 proteins in Follicular Small Cleaved Cell Lymphoma model
Authors: Alan A Arnold, Amro Aboukameel, Jianyong Chen, Dajun Yang, Shaomeng Wang, Ayad Al-Katib, Ramzi M Mohammad
Journal: Molecular Cancer (2008)

Abstract Elevated expression of anti-apoptotic Bcl-2 family proteins have been linked to a poor survival rate of patients with Follicular Lymphoma (FL). This prompted us to evaluate a very potent non-peptidic Small-Molecule Inhibitor (SMI) targeting Bcl-2 family proteins, Apogossypolone (ApoG2) using follicular small cleaved cell lymphoma cell line (WSU-FSCCL) and cell isolated from lymphoma patients. ApoG2 inhibited the growth of WSU-FSCCL significantly with a 50% growth inhibition of cells (IC 50 ) of 109 nM and decreased cell number of fresh lymphoma cells. ApoG2 activated caspases-9, -3, and -8, and the cleavage of Poly (ADP-ribose) polymerase (PARP) and Apoptosis Inducing Factor (AIF). In the WSU-FSCCL-SCID xenograft model, ApoG2 showed a significant anti-lymphoma effect, with %ILS of 84% in the intravenous and 63% in intraperitoneal treated mice. These studies suggest that ApoG2 can be an effective therapeutic agent against FL.
Concentrations of apolipoproten AI, AII, and E in plasma and lipoprotein fractions of alcoholic patients: Gender differences in the effects of alcohol
Authors: Renee C. Lin, Barbara A. Miller, Timothy J. Kelly
Journal: Hepatology (1995)

Previous studies have shown that plasma levels of high-density lipoprotein (HDL) cholesterol and the two major protein components of HDLs, i.e., apolipoproteins AI and AII, were elevated in male alcoholic patients without serious liver injury. By contrast, alcohol effect on apolipoprotein E remains unclear. Apolipoprotein E is a major component of very low-density lipoprotein (VLDL) and a minor component of human high-density lipoprotein. It plays a critical role in lipoprotein metabolism through cellular lipoprotein receptors. Furthermore, previous works were carried out mostly with male subjects, whereas alcohol effects on serum apolipoproteins in female subjects have not yet been adequately addressed. In this study, we have raised antibodies specifically to recognize human apolipoprotein AI, AII, and E, respectively, to quantify apolipoprotein concentrations in plasma and lipoprotein fractions of male and female alcoholic patients. We have also measured plasma apolipoprotein concentrations in patients who had abstained from alcohol while in the hospital. Our results showed the following: (1) plasma concentrations of apolipoprotein AI and AII were significantly elevated yet plasma apolipoprotein E decreased (33%) significantly (P < .01) in male alcoholic patients; (2) apolipoprotein AI concentrations in female nondrinking control subjects were higher than in male controls, and the concentrations of apolipoprotein AI in female alcoholic patients were not significantly elevated over those of female controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Lymph-migrating, tissue-derived dendritic cells are minor constituents within steady-state lymph nodes
Authors: Claudia Jakubzick, Milena Bogunovic, Anthony J. Bonito, Emma L. Kuan, Miriam Merad, Gwendalyn J. Randolph
Journal: The Journal of Experimental Medicine (2008)

Observations that dendritic cells (DCs) constitutively enter afferent lymphatic vessels in many organs and that DCs in some tissues, such as the lung, turnover rapidly in the steady state have led to the concept that a major fraction of lymph node DCs are derived from migratory DCs that enter the lymph node through upstream afferent lymphatic vessels. We used the lysozyme M-Cre reporter mouse strain to assess the relationship of lymph node and nonlymphoid organ DCs. Our findings challenge the idea that a substantial proportion of lymph node DCs derive from the upstream tissue during homeostasis. Instead, our analysis suggests that nonlymphoid organ DCs comprise a major population of DCs within lymph nodes only after introduction of an inflammatory stimulus.
Three- vs Four-Drug Antiretroviral Regimens for the Initial Treatment of HIV-1 Infection&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;
Authors: Roy M. Gulick
Journal: JAMA (2006)

Three-drug antiretroviral regimens are standard of care for initial treatment of human immunodeficiency virus 1 (HIV-1) infection, but a 4-drug regimen could improve antiretroviral activity and be more effective than a 3-drug regimen.To compare the safety/efficacy of 3-drug vs 4-drug regimens for initial treatment of HIV-1 infection.The AIDS Clinical Trials Group (ACTG) A5095 study, a randomized, double-blind, placebo-controlled study with enrollment and follow-up conducted from March 22, 2001, to March 1, 2005, and enrolling treatment-naive, HIV-1-infected patients with HIV-1 RNA levels of 400 copies/mL or greater from US clinical trials units of the ACTG.Zidovudine/lamivudine plus efavirenz (3-drug regimen) vs zidovudine/lamivudine/abacavir plus efavirenz (4-drug regimen).Time to virologic failure (defined as time to first of 2 successive HIV-1 RNA levels > or =200 copies/mL at or after week 16), CD4 cell count changes, and grade 3 or 4 adverse events. HIV-1 RNA data were intent-to-treat, regardless of treatment changes.Seven hundred sixty-five patients with a baseline mean HIV-1 RNA level of 4.86 log10 (72,444) copies/mL and CD4 cell count of 240 cells/mm3 were randomized. After a median 3-year follow-up, 99 (26%) of 382 and 94 (25%) of 383 patients receiving the 3-drug and 4-drug regimens, respectively, reached protocol-defined virologic failure; time to virologic failure was not significantly different (hazard ratio, 0.95; 97.5% confidence interval, 0.69-1.33; P = .73). In planned subgroup analyses, increased risk for virologic failure was seen in non-Hispanic black patients (adjusted hazard ratio, 1.66; 95% confidence interval, 1.18-2.34; P = .003). At 3 years, the HIV-1 RNA level was less than 200 copies/mL in 152 (90%) of 169 and 143 (92%) of 156 patients receiving the 3-drug and 4-drug regimens, respectively (P = .59), and less than 50 copies/mL in 144 (85%) of 169 and 137 (88%) of 156 patients (P = .39). CD4 cell count increases and grade 3 or 4 adverse events were not significantly different.In treatment-naive patients, there were no significant differences between the 3-drug and 4-drug antiretroviral regimens; overall, at least approximately 80% of patients had HIV-1 RNA levels less than 50 copies/mL through 3 years. These results support current guidelines recommending 2 nucleosides plus efavirenz for initial treatment of HIV-1 infection; adding abacavir as a fourth drug provided no additional benefit.clinicaltrials.gov Identifier: NCT00013520.