tbuckley/cabot-search huggingface dataset:
Angiotensin II Type 2 Receptor Is Essential for Left Ventricular Hypertrophy and Cardiac Fibrosis in Chronic Angiotensin II–Induced Hypertension
Authors: Sahoko Ichihara, Takaaki Senbonmatsu, Edward Price, Toshihiro Ichiki, F. Andrew Gaffney, Tadashi Inagami
Journal: Circulation (2001)

Background The roles of angiotensin II (Ang II) in the regulation of heart function under normal and pathological conditions have been well documented. Although 2 types of Ang II receptor (AT 1 and AT 2 ) are found in various proportions, most studies have focused on AT 1 -coupled events. In the present study, we examined the hypothesis that signaling by AT 2 is important to the development of left ventricular hypertrophy and cardiac fibrosis by Ang II infusion in mice lacking the AT 2 gene ( Agtr 2−/Y). Methods and Results Male Agtr 2−/Y and age-matched wild-type (WT) mice were treated long-term with Ang II, infused at a rate of 4.2 ng · kg −1 · min −1 for 3 weeks. Ang II elevated systolic blood pressure to comparable levels in Agtr 2−/Y and WT mice. WT mice developed prominent concentric cardiac hypertrophy, prominent fibrosis, and impaired diastolic relaxation after Ang II infusion. In contrast, there was no cardiac hypertrophy in Agtr 2−/Y mice. Agtr 2−/Y mice, however, did not show signs of heart failure or impairment of ventricular relaxation and only negligible fibrosis after Ang II infusion. The absence of fibrosis may be a clue to the absence of impairment in ventricular relaxation and account for the normal left ventricular systolic and diastolic performances in Agtr 2−/Y mice. Conclusions Chronic loss of AT 2 by gene targeting abolished left ventricular hypertrophy and cardiac fibrosis in mice with Ang II–induced hypertension.
REHABILITATION EXERCISES FOR ATHLETES WITH BICEPS PATHOLOGY AND SLAP LESIONS: A CONTINUUM OF EXERCISES WITH INCREASING LOAD ON THE BICEPS
Authors: A Cools, D Borms, S Cottens, M Himpe, S Meersdom, B Cagnie
Journal: British Journal of Sports Medicine (2014)

Background Although conservative treatment is often recommended in biceps related pathology and SLAP lesions in overhead athletes, a progressive exercise protocol with controlled low to moderate load on the biceps has not been described yet. Objective To describe a continuum of exercises with progressive low to moderate load on the biceps, based on EMG analysis. Design Descriptive laboratory study. Participants Non-injured participants, age 22.3 yrs (±1.3 yrs). Risk factor assessment Electromyographic (EMG) activity of 8 muscles (upper (UT), middle (MT), lower (LT) trapezius, serratus anterior (SA), anterior (DA) and posterior (DP) portions of the deltoid, biceps (BB) and triceps (TB) brachii) was measured in 32 healthy subjects performing 16 commonly described shoulder rehabilitation exercises, using surface electromyography. Main outcome measurements EMG activity, normalized to MIVC. Results Out of the 16 exercises, 13 show low (&lt;20% MIVC) and 3 moderate (20-50% MIVC) EMG activity in the BB. Based on the results, a ranking is presented of the exercises with EMG levels between 2.2±1.24 (during internal rotation against resistance in 90° of shoulder abduction) and 35.9±18.82 (during forward flexion in external rotation and supination) % MIVC. Conclusion A continuum of exercises may be used in the rehabilitation of biceps pathology and SLAP lesions, based on the EMG activity of the BB, varying from very low to moderate load. The results may assist the clinician in the appropriate choice of exercises in a graded rehabilitation program of biceps related pathology.
Improving the Specificity of Screening for Lethal Prostate Cancer Using Prostate-specific Antigen and a Panel of Kallikrein Markers: A Nested Case–Control Study
Authors: Pär Stattin, Andrew J. Vickers, Daniel D. Sjoberg, Robert Johansson, Torvald Granfors, Mattias Johansson, Kim Pettersson, Peter T. Scardino, Göran Hallmans, Hans Lilja
Journal: European Urology (2015)

A disadvantage of prostate-specific antigen (PSA) for the early detection of prostate cancer (PCa) is that many men must be screened, biopsied, and diagnosed to prevent one death.
Functional Characterization of the Candidate Tumor Suppressor Gene <b> <i>NPRL2</i> </b>/<b> <i>G21</i> </b> Located in 3p21.3C
Authors: Jingfeng Li, Fuli Wang, Klas Haraldson, Alexey Protopopov, Fuh-Mei Duh, Laura Geil, Igor Kuzmin, John D. Minna, Eric Stanbridge, Eleonora Braga, Vladimir I. Kashuba, George Klein, Michael I. Lerman, Eugene R. Zabarovsky
Journal: Cancer Research (2004)

Initial analysis identified the NPRL2/G21 gene located in 3p21.3C, the lung cancer region, as a strong candidate tumor suppressor gene. Here we provide additional evidence of the tumor suppressor function of NPRL2/G21. The gene has highly conserved homologs/orthologs ranging from yeast to humans. The yeast ortholog, NPR2, shows three highly conserved regions with 32 to 36% identity over the whole length. By sequence analysis, the main product of NPRL2/G21 encodes a soluble protein that has a bipartite nuclear localization signal, a protein-binding domain, similarity to the MutS core domain, and a newly identified nitrogen permease regulator 2 domain with unknown function. The gene is highly expressed in many tissues. We report inactivating mutations in a variety of tumors and cancer cell lines, growth suppression of tumor cells with tet-controlled NPRL2/G21 transgenes on plastic Petri dishes, and suppression of tumor formation in SCID mice. Screening of 7 renal, 5 lung, and 7 cervical carcinoma cell lines showed homozygous deletions in the 3' end of NPRL2 in 2 renal, 3 lung, and 1 cervical (HeLa) cell line. Deletions in the 3' part of NPRL2 could result in improper splicing, leading to the loss of the 1.8 kb functional NPRL2 mRNA. We speculate that the NPRL2/G21 nuclear protein may be involved in mismatch repair, cell cycle checkpoint signaling, and activation of apoptotic pathway(s). The yeast NPR2 was shown to be a target of cisplatin, suggesting that the human NPRL2/G21 may play a similar role. At least two homozygous deletions of NPRL2/G21 were detected in 6 tumor biopsies from various locations and with microsatellite instability. This study, together with previously obtained results, indicates that NPRL2 is a multiple tumor suppressor gene.
General and Regional Circulatory Effects of Synthetic Bradykinin in Man
Authors: HERMES A. KONTOS, JOSEPH H. MAGEE, WILLIAM SHAPIRO, JOHN L. PATTERSON
Journal: Circulation Research (1964)

The general and regional circulatory effects of synthetic bradykinin were investigated in 19 healthy volunteers. During intravenous infusion of bradykinin (25 µg/min) mean arterial pressure decreased initially, but returned to control levels within a few minutes. Heart rate increased during the hypotensive period, but subsequently returned toward preinfusion levels. Cardiac output increased, mainly as a result of increased stroke volume, and systemic vascular resistance decreased. Blood flow to hand increased during such infusions of bradykinin, but blood flow to forearm was not altered significantly. Intravenous infusions of 40 µg/min produced an increase in blood flow to the forearm, resulting solely from cutaneous vasodilatation in most subjects. The distensibility of hand veins increased both during intravenous infusions of 25 µg/min and during infusions of 0.2 µg/min into the brachial artery. Renal clearance of inulin was slightly decreased during infusion of 25 µg/ min bradykinin; there was no detectable change of PAH clearance.
Incidence and Outcomes in Acute Kidney Injury
Authors: Tariq Ali, Izhar Khan, William Simpson, Gordon Prescott, John Townend, William Smith, Alison MacLeod
Journal: Journal of the American Society of Nephrology (2007)

Epidemiological studies of acute kidney injury (AKI) and acute-on-chronic renal failure (ACRF) are surprisingly sparse and confounded by differences in definition. Reported incidences vary, with few studies being population-based. Given this and our aging population, the incidence of AKI may be much higher than currently thought. We tested the hypothesis that the incidence is higher by including all patients with AKI (in a geographical population base of 523,390) regardless of whether they required renal replacement therapy irrespective of the hospital setting in which they were treated. We also tested the hypothesis that the Risk, Injury, Failure, Loss, and End-Stage Kidney (RIFLE) classification predicts outcomes. We identified all patients with serum creatinine concentrations ≥150 μmol/L (male) or ≥130μmol/L (female) over a 6-mo period in 2003. Clinical outcomes were obtained from each patient's case records. The incidences of AKI and ACRF were 1811 and 336 per million population, respectively. Median age was 76 yr for AKI and 80.5 yr for ACRF. Sepsis was a precipitating factor in 47% of patients. The RIFLE classification was useful for predicting full recovery of renal function (P < 0.001), renal replacement therapy requirement (P < 0.001), length of hospital stay [excluding those who died during admission (P < 0.001)], and in-hospital mortality (P = 0.035). RIFLE did not predict mortality at 90 d or 6 mo. Thus the incidence of AKI is much higher than previously thought, with implications for service planning and providing information to colleagues about methods to prevent deterioration of renal function. The RIFLE classification is useful for identifying patients at greatest risk of adverse short-term outcomes.
Detection of three distinct patterns of T helper cell dysfunction in asymptomatic, human immunodeficiency virus-seropositive patients. Independence of CD4+ cell numbers and clinical staging.
Authors: M Clerici, N I Stocks, R A Zajac, R N Boswell, D R Lucey, C S Via, G M Shearer
Journal: Journal of Clinical Investigation (1989)

We have tested the T helper cell (TH) potential of asymptomatic, HIV seropositive (HIV+) patients, using an in vitro assay for IL-2 production. Peripheral blood leukocytes (PBL) from 74 HIV+ patients and 70 HIV- control donors were tested for TH function when stimulated with influenza A virus (FLU), tetanus toxoid (TET), HLA alloantigens (ALLO), or PHA. Of the HIV+ patients, four different response patterns were observed: (a) patients who responded to all four stimuli (16%); (b) patients who were selectively unresponsive to FLU and TET, but responded to ALLO and PHA (54%); (c) patients who were unresponsive to FLU, TET, or ALLO, but responsive to PHA (16%); and (d) patients who failed to respond to any of these stimuli (14%). Our results indicate a time-dependent progression from a stage responsive to all four stimuli to a stage unresponsive to any of the stimuli tested, progressing in the order outlined above. The earliest TH defect is the loss of responses to FLU and TET, indicating a selective defect in CD4+ MHC self-restricted TH function. The later loss of ALLO and PHA IL-2 responses suggests more severe TH dysfunction involving both CD4+ and CD8+ T cells. None of these patterns of TH unresponsiveness in asymptomatic HIV+ individuals were correlated with CD4+ cell numbers nor with Walter Reed staging criteria. This study indicates that the in vitro TH assay used can detect multiple stages of immune dysregulation early in the course of HIV infection and raises the possibility that staging of HIV+ patients should include in vitro TH functional analyses of the type described here.
Sleep {middle dot} 1: Obstructive sleep apnoea/hypopnoea syndrome: definitions, epidemiology, and natural history
Authors: J R Stradling
Journal: Thorax (2003)

Arguments over the definition of obstructive sleep apnoea/hypopnoea syndrome (OSAHS) have still not been satisfactorily resolved. As a result, robust estimates of the prevalence of OSAHS are not possible. New approaches are needed to identify those who have "CPAP responsive" disease, enabling more accurate estimates to be made of the prevalence of the sleep apnoea syndrome in the community.
Active and Passive Immunotherapy for Lymphoma: Proving Principles and Improving Results
Authors: Joshua Brody, Holbrook Kohrt, Aurelien Marabelle, Ronald Levy
Journal: Journal of Clinical Oncology (2011)

Conventional chemotherapy for lymphoma has advanced greatly over the past 50 years, changing some lymphoma subtypes from uniformly lethal to curable; however, the majority of lymphomas in patients remain incurable, and there is a need for novel therapies with less toxicity and more specific targeting of tumor cells. The vertebrate immune system has evolved the capacity for such specific targeting through the B-cell and T-cell receptors; passive immunotherapies utilizing these receptors, such as monoclonal antibodies (mAbs) or T cells, have shown efficacy in treating lymphomas. The first generation of mAb-based therapies has transformed the standard of care for lymphoma, and newer antibodies may improve on this approach. Clinical activity has been shown by T cells bearing receptors that target viral antigens as well as T cells bearing re-engineered receptors that target antigens recognized by antibodies. Active immunotherapies, such as vaccines and immune checkpoint blockades, have prolonged survival in certain solid tumors and are being actively pursued to treat lymphoma. A variety of vaccines (eg, protein- and cell-based vaccines) are being tested in ongoing trials, and the most recent iterations show therapeutic activity. Newer trials are addressing the problem of tumor-induced immunosuppression by the use of antibodies against immunologic checkpoints or by the reinfusion of primed T cells after lymphodepletion, a process we refer to as immunotransplantation. Herein, we discuss results of the various immunotherapy strategies applied to lymphoma and the ongoing approaches for their improvement.
Frontostriatal Abnormalities in Adolescents With Bipolar Disorder: Preliminary Observations From Functional MRI
Authors: Hilary P. Blumberg, Andrés Martin, Joan Kaufman, Hoi-Chung Leung, Pawel Skudlarski, Cheryl Lacadie, Robert K. Fulbright, John C. Gore, Dennis S. Charney, John H. Krystal, Bradley S. Peterson
Journal: American Journal of Psychiatry (2003)

This study investigated whether the functional abnormalities in prefrontal systems observed in adult bipolar disorder are manifested in adolescents with this illness.Ten adolescents with bipolar disorder and 10 healthy comparison subjects participated in a color-naming Stroop task during event-related functional magnetic resonance imaging.Signal increases in the left putamen and thalamus were significantly greater in the bipolar disorder group than in the healthy group. Age correlated positively with signal increases in the bilateral rostroventral prefrontal cortex and the striatum in the healthy group but not in the bipolar disorder group. In the bipolar disorder subjects, depressive symptoms correlated positively with signal increases in the ventral striatum.These findings suggest the presence of dysfunction in the subcortical portions of the frontostriatal circuits in adolescents with bipolar disorder. The absence of the prefrontal abnormalities that were observed previously in adults and the absence of the age-related increases in prefrontal activity observed in normal comparison subjects suggest that a developmental disturbance in prefrontal function may emerge in bipolar disorder over the course of adolescence.
Recessive disorders and consanguineous marriage
Authors: John W T Benson
Journal: BMJ (2005)

Rationing in response to NHS deficits: rural patients are likely to be affected most See News, p 1426Editor-News that pressing financial problems have caused NHS trusts in Suffolk to set new "thresholds" to treatments such as joint replacements reinforces concerns raised by a recent BMA survey of medical directors of trusts in which over a third of respondents anticipated reductions of key services in response to funding shortfalls. 1 2 What has hitherto escaped comment is how cuts in services are far more likely to be felt in some parts of the country than others.Deficits in the NHS are invariably presented as a problem of financial mismanagement, but the pattern of deficits shows that the current resource allocation model discriminates against particular communities.According to the recently published accounts for 2004-5, 3 89 out of 303 (30%) English primary care trusts ended the year in deficit.The table shows how 301 of these trusts are distributed accorded to fifths of deprivation and rurality.Primary care trusts serving populations that are in both the most rural and the least deprived fifth were most likely to be in financial difficulties.Seventeen of the 25 (68%) in this category were in deficit.These trusts received the lowest funding allocation per head (£995).By contrast, only 3% (one of 34) of the primary care trusts serving populations that are in both the most urban and the most deprived fifths failed to break even in 2004-5.These trusts received the highest funding allocations per head (£1405).This shows that poor financial management can at best only partly explain why some trusts are in deficit.The pattern of deficits implies that NHS funding provides insufficient resources for rural areas, for comparatively affluent areas, and, most particularly, for areas that are both rural and affluent.The risk is that such measures will result in NHS services being subject to a new postcode lottery, in which rural residents are more likely to lose out.
International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer
Authors: Marcia Irene Canto, Femme Harinck, Ralph H Hruban, George Johan Offerhaus, Jan-Werner Poley, Ihab Kamel, Yung Nio, Richard S Schulick, Claudio Bassi, Irma Kluijt, Michael J Levy, Amitabh Chak, Paul Fockens, Michael Goggins, Marco Bruno
Journal: Gut (2012)

<h3>Background</h3> Screening individuals at increased risk for pancreatic cancer (PC) detects early, potentially curable, pancreatic neoplasia. <h3>Objective</h3> To develop consortium statements on screening, surveillance and management of high-risk individuals with an inherited predisposition to PC. <h3>Methods</h3> A 49-expert multidisciplinary international consortium met to discuss pancreatic screening and vote on statements. Consensus was considered reached if ≥75% agreed or disagreed. <h3>Results</h3> There was excellent agreement that, to be successful, a screening programme should detect and treat T1N0M0 margin-negative PC and high-grade dysplastic precursor lesions (pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm). It was agreed that the following were candidates for screening: first-degree relatives (FDRs) of patients with PC from a familial PC kindred with at least two affected FDRs; patients with Peutz–Jeghers syndrome; and <i>p16</i>, <i>BRCA</i>2 and hereditary non-polyposis colorectal cancer (HNPCC) mutation carriers with ≥1 affected FDR. Consensus was not reached for the age to initiate screening or stop surveillance. It was agreed that initial screening should include endoscopic ultrasonography (EUS) and/or MRI/magnetic resonance cholangiopancreatography not CT or endoscopic retrograde cholangiopancreatography. There was no consensus on the need for EUS fine-needle aspiration to evaluate cysts. There was disagreement on optimal screening modalities and intervals for follow-up imaging. When surgery is recommended it should be performed at a high-volume centre. There was great disagreement as to which screening abnormalities were of sufficient concern to for surgery to be recommended. <h3>Conclusions</h3> Screening is recommended for high-risk individuals, but more evidence is needed, particularly for how to manage patients with detected lesions. Screening and subsequent management should take place at high-volume centres with multidisciplinary teams, preferably within research protocols.
Dietary salt loading decreases the expressions of neuronal-type nitric oxide synthase and renin in the juxtaglomerular apparatus of angiotensinogen gene-knockout mice.
Authors: M Kihara, S Umemura, M Yabana, Y Sumida, N Nyui, K Tamura, T Kadota, R Kishida, K Murakami, A Fukamizu, M Ishii
Journal: Journal of the American Society of Nephrology (1998)

The present study investigates whether neuronal type nitric oxide synthase (N-NOS) in the macula densa participates in the regulation of renal renin expression during altered dietary salt intake in angiotensinogen gene-knockout (Atg-/-) mice. Wild-type (Atg+/+) and Atg+/+ mice were fed a low-salt (0.04% NaCl), normal-salt (0.3% NaCl), or high-salt (4% NaCl) diet for 2 wk. Histochemical staining for NADPH diaphorase (NADPHd) and renin were analyzed morphometrically. Levels of N-NOS and renin mRNA in renal cortical tissues were determined by reverse transcription-PCR and Northern blot analysis, respectively. In animals fed a normal-salt diet, the renal expressions of N-NOS and renin were markedly increased in Atg-/- mice compared with Atg+/+ mice. When mutant mice were fed a high-salt diet, the signal intensity of the NADPHd reaction and the number of positively stained macula densa cells were significantly decreased. The levels of renal cortical N-NOS mRNA were also suppressed by the treatment. These changes were paralleled by decreases in renal renin-immunoreactive areas and the levels of renin mRNA. On the other hand, salt restriction did not produce further significant increases in the renal N-NOS and renin expressions in mutant mice, whereas a parallel inverse relationship was observed between these enzyme expressions and the levels of salt intake in wild-type mice. These results suggest that the N-NOS expression in the macula densa is inversely regulated by salt intake and that the enzyme activity is functionally linked to renal renin production. Salt-modulated renal N-NOS and renin expressions are independent on angiotensin formation in Atg-/- mice.
Variability of Hormone Concentrations and Ratios in Commercial Sera Used for Tissue Culture2
Authors: Henry J. Esber, I. John Payne, Arthur E. Bogden
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Variability of Hormone Concentrations and Ratios in Commercial Sera Used for Tissue Culture Get access Henry J. Esber, Henry J. Esber Department of Immunobiology, Mason Research lnstitute, Worcester, Massachusetts 01608 Search for other works by this author on: Oxford Academic PubMed Google Scholar I. John Payne, I. John Payne Department of Immunobiology, Mason Research lnstitute, Worcester, Massachusetts 01608 Search for other works by this author on: Oxford Academic PubMed Google Scholar Arthur E. Bogden Arthur E. Bogden Department of Immunobiology, Mason Research lnstitute, Worcester, Massachusetts 01608 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 2, February 1973, Pages 559–562, https://doi.org/10.1093/jnci/50.2.559 Published: 01 February 1973 Article history Received: 06 October 1972 Accepted: 22 November 1972 Published: 01 February 1973
Major histocompatibility complex antigen expression on the epithelium of the developing thymus in normal and nude mice.
Authors: E J Jenkinson, W Van Ewijk, J J Owen
Journal: The Journal of Experimental Medicine (1981)

The expression and distribution of antigens coded by the K and I regions of the major histocompatibility complex in the developing thymus of normal and nude mice has been investigated using monoclonal antibodies. Both immunohistological studies of intact rudiments and in vitro labeling of cultures derived from microdissected rudiments indicate that, while K region antigens are present on epithelial and mesenchymal elements, I region antigens are only detectable on the epithelium. This view is also substantiated by the selective absence of I region antigens in the abnormal nude thymic rudiment where the defect is considered to be epithelial in nature. The findings are considered in relation to the role of the thymus in providing an environment for the differentiation and selection of developing T cells, and it is proposed that the Ia-expressing epithelial elements play a central role in these functions.