tbuckley/cabot-search huggingface dataset:
EFFECTS OF HUMAN GROWTH HORMONE ON LEVELS OF BLOOD AND URINARY CARBOHYDRATE AND FAT METABOLITES IN MAN *
Authors: Dorothy H. Henneman, Philip H. Henneman
Journal: Journal of Clinical Investigation (1960)

In an accompanying paper (1) human growth hormo.ne(HGH) was reported to have stimulated the rate of linear growth, produced retention of nitrogen, phosphorus, magnesium, calcium, so- dium and potassium, and perhaps increased the rate of fat mobilization in ten human subjects.This paper describes the response of blood and urinary levels of fat and carbohydrate intermediary metabolites in seven of these and in one infant with hyperinsulinism.1 Some effects of HGH on carbohydrate and fat metabolism have already been published.Raben and Hollenberg (2) observed a prompt and significant rise in plasma free fatty acids (FFA).Beck, McGarry, Dyrenfurth and Venning (3) re- ported alterations in glucose tolerance in four of six patients and Ikkos, Luft and Gemzell (4) in two of two patients.Ikkos and associates also observed elevations in ketone bodies in three of four patients.The data to be reported in general confirm these observations and include the simul- taneous measurements of blood and urinary glu- cose, lactate, pyruvate, citrate, a-ketoglutarate, free fatty acids and ketones during short and long- term HGH therapy. MATERIAL AND METHODSThe clinical features of the patients studied are reported elsewhere (1).The subjects include 5 patients
Focal Segmental Glomerulosclerosis in Nephrotic Adults
Authors: Micky J. Chun, Stephen M. Korbet, Melvin M. Schwartz, Edmund J. Lewis
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. The histopathologic diagnosis of primary focal segmental glomerulosclerosis (FSGS) has come to include a number of histologic lesions (variants), but the prognostic significance of these discrete lesions is controversial because published information regarding the presentation, course, and response to treatment is limited. A retrospective analysis was conducted of 87 nephrotic adult patients with biopsy-proven primary FSGS. Patients were categorized on the basis of histologic criteria into those with a classic scar (36 patients), the cellular or collapsing lesion (40 patients), or the tip lesion (11 patients) of FSGS to evaluate differences in presentation, response to therapy, and clinical outcomes. The clinical features at biopsy were similar among the three groups with the exception that patients with the tip lesion were older and patients with the collapsing lesion had more severe proteinuria. Over the course of follow-up, 63% of patients treated attained remission and the response to steroid therapy was similar among the groups (classic scar 53% versus collapsing lesion 64% versus tip lesion 78%; P = 0.45). The overall renal survival was significantly better for patients who entered remission compared with patients who did not enter remission (92% versus 33% at 10 yr; P < 0.0001). The renal survival at 10 yr for patients who entered remission was similar among the three groups (classic scar 100% versus tip lesion 100% versus collapsing lesion 80%; P = 0.61). In patients who did not enter remission, the renal survival at 10 yr was significantly worse for patients with collapsing lesion and tip lesion (classic scar 49% versus tip lesion 25% versus collapsing lesion 21%; P = 0.002). In conclusion, the prognosis for nephrotic FSGS patients who enter remission is excellent regardless of the histologic lesion. Because the remission rate after treatment is similar among patients with the histologic variants, response to therapy cannot be predicted on the basis of histology alone. Thus, nephrotic patients with primary FSGS should receive a trial of therapy irrespective of the histologic lesion when not contraindicated.
Primary prevention of food allergy in children and adults: systematic review
Authors: D. de Silva, M. Geromi, S. Halken, A. Host, S. S. Panesar, A. Muraro, T. Werfel, K. Hoffmann‐Sommergruber, G. Roberts, V. Cardona, A. E. J. Dubois, L. K. Poulsen, R. Van Ree, B. Vlieg‐Boerstra, I. Agache, K. Grimshaw, L. O'Mahony, C. Venter, S. H. Arshad, A. Sheikh
Journal: Allergy (2014)

Abstract Background Food allergies can have serious physical, social, and financial consequences. This systematic review examined ways to prevent the development of food allergy in children and adults. Methods Seven bibliographic databases were searched from their inception to September 30, 2012, for systematic reviews, randomized controlled trials, quasi‐randomized controlled trials, controlled clinical trials, controlled before‐and‐after studies, interrupted time series studies, and prospective cohort studies. Experts were consulted for additional studies. There were no language or geographic restrictions. Two reviewers appraised the studies using appropriate tools. Data were not suitable for meta‐analysis due to heterogeneity, so were narratively synthesized. Results Seventy‐four studies were included, one‐third of which were of high quality. There was no good evidence to recommend that pregnant or breastfeeding women should change their diet or take supplements to prevent allergies in infants at high or normal risk. There were mixed findings about the preventive benefits of breastfeeding for infants at high or normal risk, but there was evidence to recommend avoiding cow's milk and substituting with extensively or partially hydrolyzed whey or casein formulas for infants at high risk for the first 4 months. Soy milk and delaying the introduction of solid foods beyond 4 months did not have preventive benefits in those at high or normal risk. There was very little evidence about strategies for preventing food allergy in older children or adults. Conclusions There is much to learn about preventing food allergy, and this is a priority given the high societal and healthcare costs involved.
Hepatocyte Nuclear Factor 4α Suppresses the Development of Hepatocellular Carcinoma
Authors: Bei-Fang Ning, Jin Ding, Chuan Yin, Wei Zhong, Kun Wu, Xin Zeng, Wen Yang, Yue-Xiang Chen, Jun-Ping Zhang, Xin Zhang, Hong-Yang Wang, Wei-Fen Xie
Journal: Cancer Research (2010)

Abstract Hepatocyte nuclear factor 4α (HNF4α) is a transcription factor that plays a key role in hepatocyte differentiation and the maintenance of hepatic function, but its role in hepatocarcinogenesis has yet to be examined. Here, we report evidence of a suppressor role for HNF4α in liver cancer. HNF4α expression was progressively decreased in the diethylinitrosamine-induced rat model of liver carcinogenesis. In human liver tissues, HNF4α expression was decreased in cirrhotic tissue and further decreased in hepatocarcinoma relative to healthy tissue. Notably, an inverse correlation existed with epithelial-mesenchymal transition (EMT). Enforced expression of HNF4α attenuated hepatocyte EMT during hepatocarcinogenesis, alleviated hepatic fibrosis, and blocked hepatocellular carcinoma (HCC) occurrence. In parallel, stem cell marker gene expression was inhibited along with cancer stem/progenitor cell generation. Further, enforced expression of HNF4α inhibited activation of β-catenin, which is closely associated with EMT and hepatocarcinogenesis. Taken together, our results suggest that the inhibitory effect of HNF4α on HCC development might be attributed to suppression of hepatocyte EMT and cancer stem cell generation through an inhibition of β-catenin signaling pathways. More generally, our findings broaden knowledge on the biological significance of HNF4α in HCC development, and they imply novel strategies for HCC prevention through the manipulation of differentiation-determining transcription factors in various types of carcinomas. Cancer Res; 70(19); 7640–51. ©2010 AACR.
A Decision Rule for Diagnostic Testing in Obstructive Sleep Apnea
Authors: Willis H. Tsai, John E. Remmers, Rollin Brant, W. Ward Flemons, Jan Davies, Colin Macarthur
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Obstructive sleep apnea (OSA) is traditionally diagnosed using overnight polysomnography. Decision rules may provide an alternative to polysomnography. A consecutive series of patients referred to a tertiary sleep center underwent prospective evaluation with the upper airway physical examination protocol, followed by determination of the respiratory disturbance index using a portable monitor. Seventy-five patients were evaluated with the upper airway physical examination protocol. Historic predictors included age, snoring, witnessed apneas, and hypertension. Physical examination-based predictors included body mass index, neck circumference, mandibular protrusion, thyro-rami distance, sterno-mental distance, sterno-mental displacement, thyro-mental displacement, cricomental space, pharyngeal grade, Sampsoon-Young classification, and over-bite. A decision rule was developed using three predictors: a cricomental space of 1.5 cm or less, a pharyngeal grade of more than II, and the presence of overbite. In patients with all three predictors (17%), the decision rule had a positive predictive value of 95% (95% confidence interval [CI], 75-100%) and a negative predictive value of 49% (95% CI, 35-63%). A cricomental space of more than 1.5 cm (27% of patients) excluded OSA (negative predictive value of 100%, 95% CI, 75-100%). Comparable performance was obtained in a validation sample of 50 patients referred for diagnostic testing. This decision rule provides a simple, reliable, and accurate method of identifying a subset patients with, and perhaps more importantly, without OSA.
Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction Versus Treatment Switch
Authors: Frank Weidemann, Johannes Krämer, Thomas Duning, Malte Lenders, Sima Canaan-Kühl, Alice Krebs, Hans Guerrero González, Claudia Sommer, Nurcan Üçeyler, Markus Niemann, Stefan Störk, Michael Schelleckes, Stefanie Reiermann, Jörg Stypmann, Stefan-Martin Brand, Christoph Wanner, Eva Brand
Journal: Journal of the American Society of Nephrology (2014)

Because of the shortage of agalsidase-beta in 2009, many patients with Fabry disease were treated with lower doses or were switched to agalsidase-alfa. This observational study assessed end-organ damage and clinical symptoms during dose reduction or switch to agalsidase-alfa. A total of 105 adult patients with Fabry disease who had received agalsidase-beta (1.0 mg/kg body weight) for ≥1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=38), receive a reduced dose of 0.3–0.5 mg/kg (dose-reduction group, n=29), or switch to 0.2 mg/kg agalsidase-alfa (switch group) and were followed prospectively for 1 year. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD); changes in cardiac, renal, and neurologic function; and Fabry-related symptoms (neuropathic pain, hypohidrosis, diarrhea, and disease severity scores). Organ function and Fabry-related symptoms remained stable in the regular-dose group. In contrast, estimated GFR decreased by about 3 ml/min per 1.73 m2 (P=0.01) in the dose-reduction group, and the median albumin-to-creatinine ratio increased from 114 (0–606) mg/g to 216 (0–2062) mg/g (P=0.03) in the switch group. Furthermore, mean Mainz Severity Score Index scores and frequencies of pain attacks, chronic pain, gastrointestinal pain, and diarrhea increased significantly in the dose-reduction and switch groups. In conclusion, patients receiving regular agalsidase-beta dose had a stable disease course, but dose reduction led to worsening of renal function and symptoms. Switching to agalsidase-alfa is safe, but microalbuminuria may progress and Fabry-related symptoms may deteriorate.
Chronology of cellular events leading to derangements in function of pancreatic islets in chronic renal failure.
Authors: E Levi, G Z Fadda, P Thanakitcharu, S G Massry
Journal: Journal of the American Society of Nephrology (1992)

In chronic renal failure (CRF), a multitude of metabolic derangements occur in the pancreatic islets, resulting in impaired glucose-induced insulin secretion. These abnormalities include a rise in the basal level of cytosolic calcium ([Ca2+]i) in the islet, a decrease in their basal and stimulated ATP and ATP/ADP ratio, a reduction in the Vmax of Ca2+ATPase and Na(+)-K+ATPase, and an impaired glucose-induced calcium signal. The sequence of events that lead to these derangements and to the impairment in insulin secretion during the evolution of CRF are not defined. The study presented here examined this issue by measuring the metabolic profile of pancreatic islets weekly during the evolution of CRF over a period of 6 wk. The results show that serum levels of parathyroid hormone (PTH) begin to rise during the first week of CRF. The Vmax of Ca2+ATPase and Na(+)-K+ATPase increased during weeks 1 to 3 of CRF but fell to low levels thereafter. At week 3 of CRF, the basal level of [Ca2+]i began to rise, whereas basal and the stimulated ATP content and ATP/ADP ratio started to fall. Glucose-induced calcium signal, delta[Ca2+]i/basal [Ca2+]i, and insulin secretion became abnormally low between weeks 3 and 6 of CRF. The data allow the following formulation: as serum levels of PTH begins to rise, calcium entry into islets is augmented; this in turn will stimulate the activity of Ca2+ATPase and the Na(+)-Ca2+ exchanger, and hence, calcium extrusion out of the islets is increased. As a result, [Ca2+] remains normal during the first 2 wk of CRF.(ABSTRACT TRUNCATED AT 250 WORDS)
CHARACTERIZATION OF A C<scp>R</scp>51-LABELED ENDOTOXIN AND ITS IDENTIFICATION IN PLASMA AND URINE AFTER PARENTERAL ADMINISTRATION
Authors: Louis Chedid, Robert C. Skarnes, Monique Parant
Journal: The Journal of Experimental Medicine (1963)

The incubation of endotoxin with Na(2)Cr(51)O(4) yielded a product which was well labeled. That the label was fixed on the endotoxin itself was shown by autoradiography on specific lines of precipitation formed in agar. Ultracentrifugation at 40,000 RPM sedimented 80 per cent of the total weight of the starting Boivin preparation. Agar diffusion patterns with subsequent autoradiographs demonstrated that the chromium tag was associated only with the heavy fractions of the pellet. The supernatant contained precipitable, but unlabeled endotoxin. Toxicity measurements showed that more than 99 per cent of the total toxicity resided in the pellet fractions. The chromate-tagged endotoxin was specifically identified in plasma samples taken up to 6 hours after intravenous administration of LD(50) or sublethal doses. The endotoxin was not totally detoxified in vivo since plasma collected 6 hours after the injection of even the sublethal dose was toxic when assayed in adrenalectomized mice. The endotoxin was specifically identified in urine specimens but it was no longer toxic or radioactive. Agar diffusion experiments indicated that only degraded material was present.
Inhibition of Granulocyte-Macrophage Colony-Stimulating Factor Prevents Dissemination and Induces Remission of Juvenile Myelomonocytic Leukemia in Engrafted Immunodeficient Mice
Authors: Per O. Iversen, Ian D. Lewis, Suzanne Turczynowicz, Henrik Hasle, Charlotte Niemeyer, Kjeld Schmiegelow, Stan Bastiras, Andrea Biondi, Timothy P. Hughes, Angel F. Lopez
Journal: Blood (1997)
Purification of three cytotoxic lymphocyte granule serine proteases that induce apoptosis through distinct substrate and target cell interactions.
Authors: L Shi, C M Kam, J C Powers, R Aebersold, A H Greenberg
Journal: The Journal of Experimental Medicine (1992)

We recently reported the purification of a lymphocyte granule protein called "fragmentin," which was identified as a serine protease with the ability to induce oligonucleosomal DNA fragmentation and apoptosis (Shi, L., R. P. Kraut, R. Aebersold, and A. H. Greenberg. 1992. J. Exp. Med. 175:553). We have now purified two additional proteases with fragmentin activity from lymphocyte granules. The three proteases are of two types; one has the unusual ability to cleave a tripeptide thiobenzyl ester substrate after aspartic acid, similar to murine cytotoxic cell protease I/granzyme B, while two are tryptase-like, preferentially hydrolyzing after arginine, and bear some homology to human T cell granule tryptases, granzyme 3, and Hanukah factor/granzyme A. Using tripeptide chloromethyl ketones, the pattern of inhibition of DNA fragmentation corresponded to the inhibition of peptide hydrolysis. The Asp-ase fragmentin was blocked by aspartic acid-containing tripeptide chloromethyl ketones, while the tryptase fragmentins were inhibited by arginine-containing chloromethyl ketones. The two tryptase fragmentins were slow acting and were partly suppressed by blocking proteins synthesis with cycloheximide in the YAC-1 target cell. In contrast, the Asp-ase fragmentin was fast acting and produced DNA damage in the absence of protein synthesis. Using a panel of unrelated target cells of lymphoma, thymoma, and melanoma origin, distinct patterns of sensitivity to the three fragmentins were observed. Thus, these three granule proteases make up a family of fragmentins that activate DNA fragmentation and apoptosis by acting on unique substrates in different target cells.
2015 Gout Classification Criteria: An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative
Authors: Tuhina Neogi, Tim L. Th. A. Jansen, Nicola Dalbeth, Jaap Fransen, H. Ralph Schumacher, Dianne Berendsen, Melanie Brown, Hyon Choi, N. Lawrence Edwards, Hein J. E. M. Janssens, Frédéric Lioté, Raymond P. Naden, George Nuki, Alexis Ogdie, Fernando Perez‐Ruiz, Kenneth Saag, Jasvinder A. Singh, John S. Sundy, Anne‐Kathrin Tausche, Janitzia Vaquez‐Mellado, Steven A. Yarows, William J. Taylor
Journal: Arthritis & Rheumatology (2015)

Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout.An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multicriterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set.The entry criterion for the new classification criteria requires the occurrence of at least 1 episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (i.e., synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy computed tomography, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively).The new classification criteria, developed using a data-driven and decision analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout.
Breast cancer mortality in Copenhagen after introduction of mammography screening: cohort study
Authors: Anne Helene Olsen, Sisse H Njor, Ilse Vejborg, Walter Schwartz, Peter Dalgaard, Maj-Britt Jensen, Ulla Brix Tange, Mogens Blichert-Toft, Fritz Rank, Henning Mouridsen, Elsebeth Lynge
Journal: BMJ (2005)

To evaluate the effect on breast cancer mortality during the first 10 years of the mammography service screening programme that was introduced in Copenhagen in 1991.Cohort study.The mammography service screening programme in Copenhagen, Denmark.All women ever invited to mammography screening in the first 10 years of the programme. Historical, national, and historical national control groups were used.The main outcome measure was breast cancer mortality. We compared breast cancer mortality in the study group with rates in the control groups, adjusting for age, time period, and region.Breast cancer mortality in the screening period was reduced by 25% (relative risk 0.75, 95% confidence interval 0.63 to 0.89) compared with what we would expect in the absence of screening. For women actually participating in screening, breast cancer mortality was reduced by 37%.In the Copenhagen programme, breast cancer mortality was reduced without severe negative side effects for the participants.
Photodynamic Therapy–Induced Cell Surface Expression and Release of Heat Shock Proteins: Relevance for Tumor Response
Authors: Mladen Korbelik, Jinghai Sun, Ivana Cecic
Journal: Cancer Research (2005)

Almost instantaneously after the treatment of mouse SCCVII tumor cells with Photofrin-based photodynamic therapy (PDT), a fraction (15-25%) of total cellular heat shock protein 70 (HSP70) became exposed at the cell surface. The level of this surface-expressed HSP70 then remained unchanged for the next 6 hours and persisted at lower levels even at 18 hours after PDT. A similar induction of surface HSP70 expression was found with PDT-treated human umbilical vein endothelial cells. The same analysis for several other HSPs revealed the induced surface expression of HSP60 and GRP94, but not GRP78, on PDT-treated SCCVII cells. A fraction of total HSP70 existing in SCCVII cells at the time of PDT treatment was promptly (within 1 hour) released from cells after high treatment doses, whereas even lower PDT doses induced a substantial HSP70 release at later time intervals. Macrophages coincubated with PDT-treated SCCVII cells displayed elevated levels of both HSP70 and GRP94 on their surface and were stimulated to produce tumor necrosis factor alpha, whose production was inhibited by the presence of antibodies against either HSP70, Toll-like receptors 2 and 4, or specific NF-kappaB inhibitor in the coincubation medium. The induction of cell surface expression and release of HSPs by PDT may represent an important event in the response of tumors to this treatment modality with a critical role in the induced inflammatory and immune responses that contribute to the therapeutic outcome.
DACT3 Is an Epigenetic Regulator of Wnt/β-Catenin Signaling in Colorectal Cancer and Is a Therapeutic Target of Histone Modifications
Authors: Xia Jiang, Jing Tan, Jingsong Li, Saul Kivimäe, Xiaojing Yang, Li Zhuang, Puay Leng Lee, Mark T.W. Chan, Lawrence W. Stanton, Edison T. Liu, Benjamin N.R. Cheyette, Qiang Yu
Journal: Cancer Cell (2008)
De novo CD5+ diffuse large B-cell lymphoma: a clinicopathologic study of 109 patients
Authors: Motoko Yamaguchi, Masao Seto, Masataka Okamoto, Ryo Ichinohasama, Naoya Nakamura, Tadashi Yoshino, Junji Suzumiya, Takuhei Murase, Ikuo Miura, Takashi Akasaka, Jun Ichi Tamaru, Ritsuro Suzuki, Yoshitoyo Kagami, Masami Hirano, Yasuo Morishima, Ryuzo Ueda, Hiroshi Shiku, Shigeo Nakamura
Journal: Blood (2002)