tbuckley/cabot-search huggingface dataset:
Growth hormone augments superoxide anion secretion of human neutrophils by binding to the prolactin receptor.
Authors: Y K Fu, S Arkins, G Fuh, B C Cunningham, J A Wells, S Fong, M J Cronin, R Dantzer, K W Kelley
Journal: Journal of Clinical Investigation (1992)

Recombinant human growth hormone (HuGH) and human prolactin (HuPRL), but not GH of bovine or porcine origin, prime human neutrophils for enhanced superoxide anion (O2-) secretion. Since HuGH, but not GH of other species, effectively binds to the HuPRL receptor (HuPRL-R), we used a group of HuGH variants created by site-directed mutagenesis to identify the receptor on human neutrophils responsible for HuGH priming. A monoclonal antibody (MAb) directed against the HuPRL-R completely abrogated O2- secretion by neutrophils incubated with either HuGH or HuPRL, whereas a MAb to the HuGH-R had no effect. The HuGH variant K172A/F176A, which has reduced affinity for both the HuGH-binding protein (BP) and the HuPRL-BP, was unable to prime human neutrophils. This indicates that priming is initiated by a ligand-receptor interaction, the affinity of which is near that defined for receptors for PRL and GH. Another HuGH variant, K168A/E174A, which has relatively low affinity for the HuPRL-BP but slightly increased affinity for the HuGH-BP, had much reduced ability to prime neutrophils. In contrast, HuGH variant E56D/R64M, which has a similar affinity as wild-type HuGH for the HuPRL-BP but a lower affinity for the HuGH-BP, primed neutrophils as effectively as the wild-type HuGH. Finally, binding of HuGH to the HuPRL-BP but not to the HuGH-BP has been shown to be zinc dependent, and priming of neutrophils by HuGH was also responsive to zinc. Collectively, these data directly couple the binding of HuGH to the HuPRL-R with one aspect of functional activation of human target cells.
The Effect of Glyburide on β-Cell Sensitivity to Glucose-Dependent Insulinotropic Polypeptide
Authors: Graydon S Meneilly, Michael Bryer-Ash, Dariush Elahi
Journal: Diabetes Care (1993)

Objective— To assess whether treatment with glyburide alters β-cell sensitivity to GIP in NIDDM patients. Research Design and Methods— We studied 5 untreated NIDDM patients in a meal study (Ensure, 240 ml/M2) and a 2-h hyperglycemic glucose clamp study (glucose 5.4 mM above fasting). From 60 to 120 min of the clamp, GIP was infused in a primed continuous manner at a rate of 2 pmol·kg−1·min−1. Subjects then were treated with glyburide. After they had been on a stable dose of medication for 1 mo, the meal study and glucose clamp studies were repeated. Results— In response to treatment, a decrease in fasting glucose and an increase in weight was observed (12.8 ± 1.8 vs. 8.5 ± 0.8 mM and 74.3 ± 6.3 vs. 76.1 ± 6.3 kg, respectively, P &amp;lt; 0.05). In response to the meal study, the AUC for glucose was less, for insulin was increased, and for GIP was unchanged after treatment (16.9 ± 2.1 vs. 12.6 ± 6.9 mM, P &amp;lt;0.05; 161 ± 47 vs. 242 ± 60 pM, P &amp;lt; 0.05; and 199 ± 22 vs. 219 ± 18 pM, respectively). During the hyperglycemic clamp, steady-state glucose and 90- to 120-min GIP values were equivalent before and after treatment (18.0 ± 1.3 vs. 18.3 ± 1.3 mM and 302 ± 59 vs. 298 ± 37 pM, respectively). The 90b–120 min insulin responses to the hyperglycemic clamp were greater after therapy (123 ± 37 vs. 283 ± 80 pM, P &amp;lt; 0.05) reflecting increased β-cell responses to GIP. Conclusions— We conclude that glyburide enhances β-cell sensitivity to GIP.
The Philippine cynomolgus monkey (Macaca fasicularis) provides a new nonhuman primate model of tuberculosis that resembles human disease
Authors: Gerald P. Walsh, Esterlina V. Tan, Eduardo C. Dela Cruz, Rodolfo M. Abalos, Laarni G. Villahermosa, Leon J. Young, Roland V. Cellona, Jerome B. Narareno, Marcus A. Horwitz
Journal: Nature Medicine (1996)
Interaliasing distance of the flow convergence surface for determining mitral regurgitant volume: a validation study in a chronic animal model
Authors: Marta Sitges, Michael Jones, Takahiro Shiota, David L. Prior, Jian Xin Qin, Hiroyuki Tsujino, Fabrice Bauer, Yong Jin Kim, Dimitri Deserranno, Neil L. Greenberg, Lisa A. Cardon, Arthur D. Zetts, Mario J. Garcia, James D. Thomas
Journal: Journal of the American College of Cardiology (2001)
Sulindac Sulfide and Exisulind Inhibit Expression of the Estrogen and Progesterone Receptors in Human Breast Cancer Cells
Authors: Jin T.E. Lim, Andrew K. Joe, Masumi Suzui, Masahito Shimizu, Muneyuki Masuda, I. Bernard Weinstein
Journal: Clinical Cancer Research (2006)

Abstract In previous studies, we found that sulindac sulfide and exisulind (sulindac sulfone, Aptosyn) cause growth inhibition, arrest cells in the G1 phase of the cell cycle, and induce apoptosis in human breast cancer cell lines. These effects were associated with decreased expression of cyclin D1. The present study focuses on the effects of sulindac sulfide and exisulind on hormone signaling components in breast cancer cells. We found that estrogen receptor (ER)–positive and progesterone receptor (PR)–positive T47D breast cancer cells were somewhat more sensitive to growth inhibition by sulindac sulfide or exisulind than ER-negative PR-negative MB-MDA-468 breast cancer cells. Further studies indicated that sulindac sulfide and exisulind caused marked down-regulation of expression of the ER and PR-A and PR-B in T47D cells. However, neither compound caused a major change in expression of the retinoic acid receptor α (RARα), RARβ, or RARα in T47D cells. Sulindac sulfide and exisulind also caused a decrease in expression of the ER in estrogen-responsive MCF-7 breast cancer cells. Both compounds also markedly inhibited estrogen-stimulated activation of an estrogen-responsive promoter in transient transfection reporter assays. Treatment of T47D cells with specific protein kinase G (PKG) activators did not cause a decrease in ER or PR expression. Therefore, although sulindac sulfide and exisulind can cause activation of PKG, the inhibitory effects of these two compounds on ER and PR expression does not seem to be mediated by PKG. Our findings suggest that the growth inhibition by sulindac sulfide and exisulind in ER-positive and PR-positive human breast cancer cells may be mediated, in part, by inhibition of ER and PR signaling. Thus, these and related compounds may provide a novel approach to the prevention and treatment of human breast cancers, especially those that are ER positive.
Residual disease detected by multidimensional flow cytometry signifies high relapse risk in patients with de novo acute myeloid leukemia: a report from Children's Oncology Group
Authors: Michael R. Loken, Todd A. Alonzo, Laura Pardo, Robert B. Gerbing, Susana C. Raimondi, Betsy A. Hirsch, Phoenix A. Ho, Janet Franklin, Todd M. Cooper, Alan S. Gamis, Soheil Meshinchi
Journal: Blood (2012)
Ann Lindsay Stewart
Authors: Simon Roth, John Wyatt, Osmund Reynolds, Duncan Hutchison
Journal: BMJ (2005)

Former consultant in perinatal medicine University College Hospital, London (b Cornwall 1930; q Bristol 1955; FRCP, FRCPCH, DCH), died from Pick's disease on 9 May 2004.​2004.




Figure 1




Ann trained in paediatrics in Bristol and Edinburgh before joining the neonatal research team at University College Hospital, London, in 1968. There she made her main interest the follow-up of high risk and premature infants, studying a large cohort into teenage and adult life, using modern scanning and psychometric techniques, latterly with the Institute of Psychiatry. In this pioneering study it became clear that the long term outcome of high risk infants could be reliably predicted from early observations and that advances in care could greatly improve survival without significant disability. She leaves a husband, Duncan Hutchison; two children; and two grandchildren.
Role of NFkappaB in the mortality of sepsis.
Authors: H Böhrer, F Qiu, T Zimmermann, Y Zhang, T Jllmer, D Männel, B W Böttiger, D M Stern, R Waldherr, H D Saeger, R Ziegler, A Bierhaus, E Martin, P P Nawroth
Journal: Journal of Clinical Investigation (1997)

Binding activity for nuclear factor kappa B (NFkappaB) consensus probes was studied in nuclear extracts from peripheral blood mononuclear cells of 15 septic patients (10 surviving and 5 not surviving). Nonsurvivors could be distinguished from survivors by an increase in NFkappaB binding activity during the observation period (P < 0.001). The increase in NFkappaB binding activity was comparable to the APACHE-II score as a predictor of outcome. Intravenous somatic gene transfer with an expression plasmid coding for IkappaBalpha was used to investigate the role of members of the NFkappaB family in a mouse model of endotoxemia. In this model, increased NFkappaB binding activity was present after injection of LPS. Intravenous somatic gene transfer with IkappaBalpha given before LPS attenuated renal NFkappaB binding activity and increased survival. Endothelial cells and monocytes/macrophages were the major target cells for somatic gene transfer, transfected with an average transfection efficiency of 20-35%. Tissue factor, a gene under regulatory control of NFkappaB, was induced by LPS. Somatic gene transfer with a reporter plasmid containing the functional tissue factor promoter demonstrated NFkappaB-dependent stimulation by LPS. Intravenous somatic gene transfer with IkappaBalpha reduced LPS-induced renal tissue factor expression, activation of the plasmatic coagulation system (decrease of thrombin-antithrombin III complexes) and renal fibrin/fibrinogen deposition. Somatic gene transfer with an expression plasmid with tissue factor cDNA in the antisense direction (in contrast to sense or vector alone) also increased survival. Furthermore, antisense tissue factor decreased renal tissue factor expression and the activation of the plasmatic coagulation system.
So what's really new about the ACL
Authors: John King
Journal: British Journal of Sports Medicine (2011)

Lecture 3 This talk will be a look at the origins of anterior cruciate ligament (ACL) mythology; a snapping noise, haemarthrosis and loss of function are characteristic of ligamentous injury; 1845! Testing for ACL laxity in near extension; 1875 Why do we test for laxity in the sagittal plane when the ACL is oblique? Why there are thousands of papers on PubMed if the problem is solved? So what is new, what is hidden because we don't read a foreign language and what does the future hold?
Joslin's Diabetes Mellitus
Authors: Roger W. Turkington
Journal: JAMA (1985)

The 12th edition of<i>Joslin's Diabetes Mellitus</i>continues the superlative tradition of eminence in the field of diabetes mellitus established by the previous editions of this monograph. Under the leadership of senior editor Alexander Marble, the 68 contributing authors have integrated all the significant advances in diabetes since the previous, 1971 edition. The contributors to the present edition are present or past members of the Joslin Diabetes Center and the New England Deaconess Hospital. As such they present a consistent viewpoint based on an 88-year tradition in patient care and a professional experience with a diabetic population of more than 140,000 patients. Nearly all the chapters of the previous edition have been given a fresh rewriting, and new chapters have been formalized on the subjects of epidemiology, immunology, animal models, metabolic fuels, exercise, education, diabetes in the elderly, hypertension, and sexual disorders. Each chapter is extensively referenced with literature citations
Phase 2 study of temozolomide and Caelyx in patients with recurrent glioblastoma multiforme
Authors: Susan L. Chua, Mark A. Rosenthal, Shirley S. Wong, David M. Ashley, Anne-marie Woods, Anthony Dowling, Lawrence M. Cher
Journal: Neuro-Oncology (2004)

Temozolomide has established activity in the treatment of recurrent glioblastoma multiforme (GBM). Caelyx (liposomal doxorubicin) has established activity in a broad range of tumors but has not been extensively evaluated in the treatment of GBM. Phase 1 data suggest that temozolomide and Caelyx can be combined safely at full dose. In this phase 2 study, combination temozolomide (200 mg/m2 orally, days 1-5) and Caelyx (40 mg/m2 i.v., day 1) was given every 4 weeks to a cohort of 22 patients with recurrent GBM, who received a total of 109 cycles (median 3.5 cycles). The median age of the patients was 55 years (range, 31-80 years), and 17 were male. All patients had received radiotherapy, but only 2 had received prior chemotherapy. One patient (5%) had a complete response, 3 patients (14%) had a partial response, and 11 patients (50%) had stable disease. The median time to progression for the cohort was 3.2 months (range, 1-13 months). Median overall survival was 8.2 months (range, 1-16+ months). Seven patients (32%) were progression free at 6 months. Hematological toxicity included grade 3/4 neutropenia in 4 patients (18%) and grade 3/4 thrombocytopenia in 4 patients (18%). Grade 3 nonhematologic toxicity included rash in 3 patients (14%), nausea and vomiting in 1 patient (4%), hypersensitivity reaction to Caelyx in 3 patients (14%), and palmar-plantar toxicity in 1 patient (4%). We conclude that the combination of temozolomide and Caelyx is well tolerated, results in a modest objective response rate, but has encouraging disease stabilization in the treatment of recurrent GBM.
Plasma and lipids from stored packed red blood cells cause acute lung injury in an animal model.
Authors: C C Silliman, N F Voelkel, J D Allard, D J Elzi, R M Tuder, J L Johnson, D R Ambruso
Journal: Journal of Clinical Investigation (1998)

Transfusion-related acute lung injury (TRALI) is a serious complication of hemotherapy. During blood storage, lipids are generated and released into the plasma. In this study, the role of these lipids in TRALI was investigated using an isolated, perfused rat lung model. Rats were pretreated with endotoxin (LPS) or saline in vivo and the lungs were isolated, ventilated, and perfused with saline, or (a) 5% (vol/ vol) fresh human plasma, (b) plasma from stored blood from the day of isolation (D.0) or from the day of outdate (D.42), (c) lipid extracts from D.42 plasma, or (d) purified lysophosphatidylcholines. Lungs from saline or LPS-pretreated rats perfused with fresh (D.0) plasma showed no pulmonary damage as compared with saline perfused controls. LPS pretreatment/D.42 plasma perfusion caused acute lung injury (ALI) manifested by dramatic changes in both pulmonary artery pressure and edema. Incubation of LPS pre-tx rats with mibefradil, a Ca2+ channel blocker, or WEB 2170, a platelet-activating factor (PAF) receptor antagonist, inhibited ALI caused by D.42 plasma. Lung histology showed neutrophil sequestration without ALI with LPS pretreatment/saline or D.0 plasma perfusion, but ALI with LPS pretreatment/D.42 plasma perfusion, and inhibition of D.42 plasma induced ALI with WEB 2170 or mibefradil. A significant increase in leukotriene E4 was present in LPS-pretreated/D.42 plasma-perfused lungs that was inhibited by WEB 2170. Lastly, significant pulmonary edema was produced when lipid extracts of D.42 plasma or lysophosphatidylcholines were perfused into LPS-pretreated lungs. Lipids caused ALI without vasoconstriction, except at the highest dose employed. In conclusion, both plasma and lipids from stored blood produced pulmonary damage in a model of acute lung injury. TRALI, like the adult respiratory distress syndrome, may be the result of two insults: one derived from stored blood and the other from the clinical condition of the patient.
A1C Variability and the Risk of Microvascular Complications in Type 1 Diabetes
Authors: Eric S. Kilpatrick, Alan S. Rigby, Stephen L. Atkin
Journal: Diabetes Care (2008)

Debate remains as to whether short- or long-term glycemic instability confers a risk of microvascular complications in addition to that predicted by mean glycemia alone. In this study, we analyzed data from the Diabetes Control and Complications Trial (DCCT) to assess the effect of A1C variability on the risk of retinopathy and nephropathy in patients with type 1 diabetes.A1C was collected quarterly during the DCCT in 1,441 individuals. The mean A1C and the SD of A1C variability after stabilization of glycemia (from 6 months onwards) were compared with the risk of retinopathy and nephropathy with adjustments for age, sex, disease duration, treatment group, and baseline A1C.Multivariate Cox regression showed that the variability in A1C added to mean A1C in predicting the risk of development or progression of both retinopathy (hazard ratio 2.26 for every 1% increase in A1C SD [95% CI 1.63-3.14], P < 0.0001) and nephropathy (1.80 [1.37-2.42], P < 0.0001), with the relationship a feature in conventionally treated patients in particular.This study has shown that variability in A1C adds to the mean value in predicting microvascular complications in type 1 diabetes. Thus, in contrast to analyses of DCCT data investigating the effect of short-term glucose instability on complication risk, longer-term fluctuations in glycemia seem to contribute to the development of retinopathy and nephropathy in type 1 diabetes.
Compression-Decompression CPR: The Biomotor-Reply
Authors: Keith G. Lurie
Journal: JAMA (1994)

<h3>In Reply.</h3> —Dr Lerman is correct that studies evaluating the addition of a suction phase to conventional CPR should not require consent as the patients are pulseless, without a palpable blood pressure, and essentially dead. We took that approach during our recent clinical trials to determine the efficacy of active compression-decompression CPR but were told (and continue to be told) by FDA officials that the handheld suction device is a "significant risk" device for this unconscious patient population. This is an absurd but not a trivial problem. When evaluating the risks of a new drug or device, the FDA still does not differentiate between the living and the nearly dead. Lerman is also correct that active chest decompression during CPR improves vital organ blood flow.<sup>1</sup>However, he is incorrect about his description of the importance of the Eisenmenger Biomotor. The Biomotor is a large shell-like device that mechanically compresses
Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma
Authors: Antonio Palumbo, Maria Teresa Ambrosini, Giulia Benevolo, Patrizia Pregno, Norbert Pescosta, Vincenzo Callea, Clotilde Cangialosi, Tommaso Caravita, Fortunato Morabito, Pellegrino Musto, Sara Bringhen, Patrizia Falco, Ilaria Avonto, Federica Cavallo, Mario Boccadoro
Journal: Blood (2006)
Treatment of Paget's Disease of Bone with Synthetic Salmon Calcitonin
Authors: J. A. Kanis, D. B. Horn, R. D. M. Scott, J. A. Strong
Journal: BMJ (1974)

Thirteen patients with painful Paget's disease of bone were treated as outpatients with low doses of synthetic salmon calcitonin 22.5-50 mug three times weekly. Treatment produced full remission of pain in a mean time of 5.5 weeks and a mean depression of serum alkaline phosphatase activity of 33%.The interval before symptomatic relief could not be predicted from the variables studied. The ultimate fall in serum alkaline phosphatase activity, however, could be predicted from the initial levels and from the early rate of decrease (P < 0.001). Biochemical resistance to treatment, which occurred in three cases, could be related to the dose and duration of treatment.Prolonged remissions of pain may occur which are not related to biochemical remission, to the dose of calcitonin, or to the duration of treatment. The side effects attributable to salmon calcitonin were transient nausea (in nine patients), transient flushing (in four), diarrhoea (in two), and rash (in one) though in only one patient did treatment have to be withdrawn prematurely because of these effects.
Navajo neuropathy: Relation to MDR3 mRNA deficiency
Authors: Daniel Ortiz, Irwin M. Arias, Laura McKellar, Vincent P. Stanton
Journal: Hepatology (2002)

recently showed depletion of mitochondrial DNA in liver from 2 patients with Navajo neuropathy (NN) and postulated that the primary defect is in nuclear regulation of mitochondrial DNA copy number.In 1997, we proposed that liver disease in children with NN may result from MDR3 deficiency (HEPATOLOGY 26(suppl):369A).Northern analysis of RNA from the liver of an affected child revealed severe reduction in MDR3 messenger RNA (mRNA) abundance (Fig. 1A), as did reversetranscription polymerase chain reaction (RT-PCR) analysis of liver biopsy samples from 3 other affected children.mRNAs for other canalicular transporters, including MDR1 and MRP2, showed no difference from normal controls.The relation between reduced MDR3 expression and the neurologic symptoms of NN was unclear.However, Northern analysis indicated that MDR3 is expressed in multiple areas of human brain (Fig. 1B).Mdr2, which is the murine form of MDR3, is expressed in the developing brain of normal mice, but is not detected in the brain or liver of mdr2Ϫ/Ϫ mice.These findings suggested that MDR3 dysfunction may also contribute to neurologic aspects of NN.To further assess whether MDR3 deficiency is a causative factor, we attempted to identify a mutation in the MDR3 gene that could account for reduced expression in NN.Although MDR3 message was severely depleted in the liver samples, a weak signal was evident by Northern and RT-PCR analysis, indicating the presence of MDR3 mRNA.Full-length complementary DNA clones were assembled from RT-PCR products generated from a patient's liver RNA.Sequence analysis of these clones failed to identify a mutation in the MDR3 mRNA, however, we could not exclude mutations in nontranscribed sequences.To determine whether mutations in MDR3 transcriptional regulatory sequences are associated with decreased mRNA levels, we obtained genomic DNA from 1 NN patient.Sequence was determined from 2.5 kb upstream of the transcriptional start site through exon 1, from the 28 MDR3 exons, and from ϳ100 to 300 nucleotides flanking each exon.No mutations were identified in these regions when the sequence of the patient was compared with that of 64 unaffected controls.These data do not exclude MDR3 as a possible causative factor in NN.Reduced levels of MDR3 expression may result from mutations in the interior of introns, more distal regions of the promoter, or a cis-acting regulatory gene located elsewhere in the genome.Alternatively, selective reduc-tion in MDR3 expression may be secondary to liver damage caused by the primary defect.The search goes on.
Comparison of cardiac catheterization and Doppler echocardiography in the decision to operate in aortic and mitral valve disease
Authors: James Slater, Aaron J. Gindea, Robin S. Freedberg, Larry A. Chinitz, Paul A. Tunick, Barry P. Rosenzweig, Howard E. Winer, Andrew Goldfarb, John L. Perez, Ephraim Glassman, Itzhak Kronzon
Journal: Journal of the American College of Cardiology (1991)
Prognostic Factors in Psychotherapy-Reply
Authors: Norman Q. Brill
Journal: JAMA (1963)

<h3>To the Editor:—</h3> Dr. Chutkow is correct in stating that patients' motivation for psychotherapy is quite varied. Some patients who apply for treatment at a psychiatric clinic do so with unrealistic expectations of an immediate magical kind of help. When this is not forthcoming, they disappear with their conviction that "no one will help them" reinforced and the feeling of abuse and abandonment more deeply ingrained. Other patients who are clearly severely ill emotionally will not even take the first step toward seeking help and seem to prefer to maintain a martyr-like, masochistic position of suffering. These patients, while secretly yearning for help, may refuse it or frustrate it when it is offered. These patients are quite different from those who somehow convey the impression that they are expecting to get well and that they are willing to cooperate with the doctor in his efforts to help them. Doctors generally