tbuckley/cabot-search huggingface dataset:
A Two-Gene Expression Ratio of Homeobox 13 and Interleukin-17B Receptor for Prediction of Recurrence and Survival in Women Receiving Adjuvant Tamoxifen
Authors: Matthew P. Goetz, Vera J. Suman, James N. Ingle, Andrea M. Nibbe, Dan W. Visscher, Carol A. Reynolds, Wilma L. Lingle, Mark Erlander, Xiao-Jun Ma, Dennis C. Sgroi, Edith A. Perez, Fergus J. Couch
Journal: Clinical Cancer Research (2006)

Abstract Purpose: In the adjuvant treatment of estrogen receptor (ER)–positive breast cancer, additional markers are needed to identify women at high risk for recurrence. Experimental Design: We examined the association between the ratio of the homeobox 13 (HOXB13) to interleukin-17B receptor (IL-17BR) expression and the clinical outcomes of relapse and survival in women with ER-positive breast cancer enrolled onto a North Central Cancer Treatment Group adjuvant tamoxifen trial (NCCTG 89-30-52). Results: Tumor blocks were obtained from 211 of 256 eligible patients, and quantitative reverse transcription-PCR profiles for HOXB13 and IL-17BR were obtained from 206 patients. The cut point for the two-gene log 2(expression ratio) that best discriminated clinical outcome (recurrence and survival) was selected and identified women with significantly worse relapse-free survival (RFS), disease-free survival (DFS), and overall survival (OS), independent of standard prognostic markers. The cut point differed as a function of nodal status [node negative (59th percentile) versus node positive (90th percentile)]. In the node-positive cohort (n = 86), the HOXB13/IL-17BR ratio was not associated with relapse or survival. In contrast, in the node-negative cohort (n = 130), a high HOXB13/IL-17BR ratio was associated with significantly worse RFS [hazard ratio (HR), 1.98; P = 0.031], DFS (HR, 2.03; P = 0.015), and OS (HR, 2.4; P = 0.014), independent of standard prognostic markers. Conclusion: A high HOXB13/IL-17BR expression ratio is associated with increased relapse and death in patients with resected node-negative, ER-positive breast cancer treated with tamoxifen and may identify patients in whom alternative therapies should be studied.
Gut-associated lymphoid tissue–primed CD4+ T cells display CCR9-dependent and -independent homing to the small intestine
Authors: Hanna Stenstad, Anna Ericsson, Bengt Johansson-Lindbom, Marcus Svensson, Jan Marsal, Matthias Mack, Dominic Picarella, Dulce Soler, Gabriel Marquez, Mike Briskin, William W. Agace
Journal: Blood (2006)
Independent Research by Early Investigators
Authors: Dan Blazer
Journal: JAMA Psychiatry (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Membranous Nephropathy — Still a Treatment Dilemma
Authors: J. Stewart Cameron
Journal: New England Journal of Medicine (1992)

Membranous nephropathy is found predominantly in middle-aged patients in association with proteinuria, which is often sufficient to induce a full nephrotic syndrome. It is characterized by immune aggregates on the outer, subepithelial aspect of the basement membrane of the glomerular capillaries and by an absence of cellular proliferation or infiltration of glomeruli by cells. Typically, it has an indolent course, evolving gradually toward renal failure in about one third to one half of patients and toward remission in the remainder.In rats, similar lesions can be induced by antibodies directed against antigens represented on the surface of glomerular epithelial cells . . .
Gene Expression Profiling Of Food-Induced Anaphylaxis Associated With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Authors: Rosa M. Munoz-Cano, Joan Bartra, Jorg Scheffel, Mariona Pascal, Barbara Dema, Antonio Valero, Ana Olivera, Cesar Picado, Juan Rivera
Journal: Journal of Allergy and Clinical Immunology (2014)
Differences between sniff mouth pressures and static maximal inspiratory mouth pressures
Authors: YF Heijdra, PN Dekhuijzen, CL van Herwaarden, HT Folgering
Journal: European Respiratory Journal (1993)

Measurements of static maximal inspiratory mouth pressure (PImax) and dynamic sniff mouth pressure (Psniff) are frequently used to assess inspiratory muscle strength. The aim of the present study was to examine, in 42 healthy subjects, the equivalence of PImax and Psniff, the influence of body posture on PImax and Psniff, and the effects of nasal patency and repeated manoeuvres on Psniff. PImax was significantly higher than Psniff, 11.05 +/- 0.42 versus 8.53 +/- 0.31 kPa. Because of the low agreement between PImax and Psniff, the two measurement methods were not interchangeable. The limits of agreement were 2.56 +/- 3.92 kPa. Sitting PImax was 11.05 +/- 0.42 kPa, and supine PImax was 9.36 +/- 0.41 kPa. Sitting and supine Psniff were 8.53 +/- 0.31 kPa and 7.52 +/- 0.33 kPa, respectively. Psniff performed with one nostril open instead of two, was higher: 9.67 +/- 0.32 kPa left and 9.62 +/- 0.32 kPa right versus 8.53 +/- 0.31 kPa when both nostrils were open. After 20-28 sniff manoeuvres, Psniff fell from 8.43 +/- 0.31 kPa to 7.83 +/- 0.30 kPa, suggesting some mechanism of inspiratory muscle fatigue. We conclude that measurement of sitting PImax yields the highest values for inspiratory muscle strength. The two measurement methods, Psniff and PImax, are not interchangeable. Measurement of Psniff is affected by nasal patency.
Long-Term Pancreas Allograft Survival in Simultaneous Pancreas-Kidney Transplantation by Era
Authors: Kayo Waki, Paul I. Terasaki, Takashi Kadowaki
Journal: Diabetes Care (2010)

OBJECTIVE To determine whether short-term improvement in pancreas graft survival with simultaneous pancreas-kidney (SPK) transplants translated into improved long-term survival, then to examine the implications of that determination. RESEARCH DESIGN AND METHODS We analyzed data for 14,311 diabetic patients who received a first SPK transplant between October 1987 and November 2007, using Kaplan-Meier analysis for graft survival rates and Cox regression analysis for year-of-transplant effect. RESULTS Overall, from 1995 to 2004, 5-year pancreas graft survival stayed about the same (70–71%). Limiting analysis to grafts that survived more than 1 year, 5-year survival from 1987 to 2004 ranged from 80 to 84%. With 1987–1989 as reference, the adjusted hazard ratio for graft failure by year of transplant increased to 1.49 (95% CI 0.97–2.30) in 2000–2004. CONCLUSIONS Long-term pancreas graft survival has remained unchanged despite the dramatic decreases in technical failures and early acute rejection rates that have contributed to prolonged SPK graft survival.
Acid suppression and upper GI cancer diagnosis Reply
Authors: D. GILLEN
Journal: Gut (2000)

Editor,—Bramble et al 1 have recently suggested that the long recognised lack of impact of open access gastroscopy on the detection of earlier upper GI cancer2 3 may be due in part to the masking of cancer by prior acid suppressive therapy. This is based on a higher rate of undiagnosed cancer at index gastroscopy in their group of patients who had received acid suppressive therapy within the six months before that gastroscopy. They conclude that clinical guidelines and endoscopy waiting times should take account of this. However, there are some serious flaws in their case series which preclude the drawing of such conclusions.

Firstly, their study is retrospective. Without prospective randomisation, one cannot ensure that their two groups are comparable. The patients who were not prescribed antisecretory therapy are more likely to have had symptoms or signs suggesting underlying cancer. Because such symptoms occur in more …
Bipolar Disorder at Prospective Follow-Up of Adults Who Had Prepubertal Major Depressive Disorder
Authors: Barbara Geller, Betsy Zimerman, Marlene Williams, Kristine Bolhofner, James L. Craney
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The authors’ goal was to conduct an adult follow-up of subjects who had participated in a study of nortriptyline for childhood depression. METHOD: The study group represented 100 (90.9%) of the original 110 subjects and included 72 subjects who had a prepubertal diagnosis of major depressive disorder and 28 normal comparison subjects. Subjects were assessed with semistructured research interviews given by research nurses who were blind to the subjects’ original diagnoses. RESULTS: In the original study, the mean age of the children with prepubertal major depressive disorder was 10.3 years (SD=1.5); at adult follow-up the mean age of these subjects was 20.7 years (SD=2.0). At follow-up, significantly more of the subjects who had prepubertal diagnoses of major depressive disorder (N=24 [33.3%]) than normal comparison subjects (none) had bipolar I disorder. Subjects who had prepubertal diagnoses of major depressive disorder also had significantly higher rates of any bipolar disorder than normal subjects (48.6% [N=35] versus 7.1% [N=2]), major depressive disorder (36.1% [N=26] versus 14.3% [N=4]), substance use disorders (30.6% [N=22] versus 10.7% [N=3]), and suicidality (22.2% [N=16] versus 3.6% [N=1]). Parental and grandparental mania predicted bipolar I disorder outcomes. CONCLUSIONS: High rates of switching to mania have implications for the treatment of depressed children. The authors discuss the reasons for their finding a higher rate of bipolar disorder in this outcome study than was found in the one other adult outcome study of prepubertal major depressive disorder.
Biochemical basis of the effect of chondroitin sulphate on osteoarthritis articular tissues
Authors: J Monfort, J-P Pelletier, N Garcia-Giralt, J Martel-Pelletier
Journal: Annals of the Rheumatic Diseases (2007)

Osteoarthritis is a chronic disease characterised by irreversible damage to joint structures, including loss of articular cartilage, osteophyte formation, alterations in the subchondral bone and synovial inflammation. Pain, functional disability and impairment of health-related quality of life are major complaints in patients with osteoarthritis. Several compounds have been investigated for their positive effects on the relief of clinical symptoms and improvement of structural changes in osteoarthritis. It has been shown that chondroitin sulphate interferes with the progression of structural changes in joint tissues and is used in the management of patients with osteoarthritis. This review summarises data from relevant reports describing the mechanisms of action of chondroitin sulphate involved in the beneficial effects of the drug.
The systemic inflammatory response syndrome is predictive of renal dysfunction in patients with non-paracetamol-induced acute liver failure
Authors: J A Leithead, J W Ferguson, C M Bates, J S Davidson, A Lee, A J Bathgate, P C Hayes, K J Simpson
Journal: Gut (2008)

Although renal dysfunction is a common complication of acute liver failure (ALF) with significant prognostic implications, the pathophysiological mechanisms remain unclear. The current hypothesis suggests that the renal dysfunction may mirror the hepatorenal syndrome of cirrhosis. However, ALF has distinct clinical characteristics and the circulatory derangement may be more comparable with sepsis.To examine the relationship between the systemic inflammatory response syndrome (SIRS) and renal dysfunction in ALF, and to identify additional risk factors for renal dysfunction.A single-centre retrospective study of 308 patients with ALF was carried out. Renal dysfunction was defined according to the RIFLE criteria for acute kidney injury.67% of patients developed renal dysfunction. On univariate analysis, renal dysfunction patients were more likely to be hypothermic (p = 0.010), had a faster heart rate (p<0.001), a higher white cell count (p = 0.001) and a lower PaCO(2) (p = 0.033). 78% of renal dysfunction patients and 53% of non-renal dysfunction patients had SIRS (p<0.001). On multivariate analysis, the risk factors for renal dysfunction were age (p = 0.024), fulfilled Kings College Hospital prognostic criteria (p<0.001), hypotension (p<0.001), paracetamol-induced ALF (p<0.001), infection (p = 0.077) and SIRS (p = 0.017). SIRS remained an independent predictor of renal dysfunction in the subgroup of patients with non-paracetamol-induced ALF (n = 91, p = 0.001). In contrast, in patients with paracetamol-induced ALF (n = 217), no relationship between SIRS and renal dysfunction was demonstrated (p = 0.373).SIRS is strongly associated with the development of renal dysfunction in patients with non-paracetamol-induced ALF. It is proposed that the systemic inflammatory cascade plays a key role in its pathogenesis.
Nicotinamide is a potent inducer of endocrine differentiation in cultured human fetal pancreatic cells.
Authors: T Otonkoski, G M Beattie, M I Mally, C Ricordi, A Hayek
Journal: Journal of Clinical Investigation (1993)

The effects of nicotinamide (NIC) on human fetal and adult endocrine pancreatic cells were studied in tissue culture. Treatment of the fetal cells with 10 mM NIC resulted in a twofold increase in DNA content and a threefold increase in insulin content. This was associated with the development of beta cell outgrowths from undifferentiated epithelial cell clusters and an increase in the expression of the insulin, glucagon, and somatostatin genes. DNA synthesis was stimulated only in the undifferentiated cells. Half-maximal doses for the insulinotropic and mitogenic effects of NIC were 5-10 and 1-2 mM, respectively. Islet-like cell clusters cultured with NIC responded to glucose stimulation with a biphasic increase in insulin release (fourfold peak), whereas control cells were unresponsive to glucose. Both control and NIC-treated cells developed into functional islet tissue after transplantation into athymic nude mice. As compared with adult islets, the insulinotropic action of NIC could only be demonstrated in the fetal cells. Our results indicate that NIC induces differentiation and maturation of human fetal pancreatic islet cells. This model should be useful for the study of molecular mechanisms involved in beta cell development.
Disruption of Hexokinase II–Mitochondrial Binding Blocks Ischemic Preconditioning and Causes Rapid Cardiac Necrosis
Authors: Kirsten M.A. Smeele, Richard Southworth, Rongxue Wu, Chaoqin Xie, Rianne Nederlof, Alice Warley, Jessica K. Nelson, Pepijn van Horssen, Jeroen P. van den Wijngaard, Sami Heikkinen, Markku Laakso, Anneke Koeman, Maria Siebes, Otto Eerbeek, Fadi G. Akar, Hossein Ardehali, Markus W. Hollmann, Coert J. Zuurbier
Journal: Circulation Research (2011)

Isoforms I and II of the glycolytic enzyme hexokinase (HKI and HKII) are known to associate with mitochondria. It is unknown whether mitochondria-bound hexokinase is mandatory for ischemic preconditioning and normal functioning of the intact, beating heart.We hypothesized that reducing mitochondrial hexokinase would abrogate ischemic preconditioning and disrupt myocardial function.Ex vivo perfused HKII(+/-) hearts exhibited increased cell death after ischemia and reperfusion injury compared with wild-type hearts; however, ischemic preconditioning was unaffected. To investigate acute reductions in mitochondrial HKII levels, wild-type hearts were treated with a TAT control peptide or a TAT-HK peptide that contained the binding motif of HKII to mitochondria, thereby disrupting the mitochondrial HKII association. Mitochondrial hexokinase was determined by HKI and HKII immunogold labeling and electron microscopy analysis. Low-dose (200 nmol/L) TAT-HK treatment significantly decreased mitochondrial HKII levels without affecting baseline cardiac function but dramatically increased ischemia-reperfusion injury and prevented the protective effects of ischemic preconditioning. Treatment for 15 minutes with high-dose (10 μmol/L) TAT-HK resulted in acute mitochondrial depolarization, mitochondrial swelling, profound contractile impairment, and severe cardiac disintegration. The detrimental effects of TAT-HK treatment were mimicked by mitochondrial membrane depolarization after mild mitochondrial uncoupling that did not cause direct mitochondrial permeability transition opening.Acute low-dose dissociation of HKII from mitochondria in heart prevented ischemic preconditioning, whereas high-dose HKII dissociation caused cessation of cardiac contraction and tissue disruption, likely through an acute mitochondrial membrane depolarization mechanism. The results suggest that the association of HKII with mitochondria is essential for the protective effects of ischemic preconditioning and normal cardiac function through maintenance of mitochondrial potential.
Phase I Dose Finding Studies of Obatoclax (GX15-070), a Small Molecule Pan-BCL-2 Family Antagonist, in Patients with Advanced Solid Tumors or Lymphoma
Authors: Jimmy J. Hwang, John Kuruvilla, David Mendelson, Michael J. Pishvaian, J.F. Deeken, Lillian L. Siu, Mark S. Berger, Jean Viallet, John L. Marshall
Journal: Clinical Cancer Research (2010)

Two phase I, single-agent studies were conducted to determine the dose and regimen of obatoclax, an antagonist of all BCL-2 antiapoptotic proteins, for evaluation in phase II trials. The two studies, GX001 and GX005, evaluated the safety and tolerability of weekly 1-hour and 3-hour infusions of obatoclax, respectively.Eligible patients in both studies were adults with solid tumor or lymphoma and performance status 0-1 for whom standard therapies were not appropriate. In the GX001 study an accelerated dose titration design was initially used with subsequent cohorts of three to six patients with 40% dose increments between levels. In the GX005 study three to six patients entered at each dose level with 40% dose increments between levels.Thirty-five patients were enrolled in studies GX001 (n = 8) and GX005 (n = 27). Clinically significant central nervous system (CNS) toxicity was observed using the 1-hour infusion schedule. The obatoclax maximum tolerated dose (MTD) in GX001 was 1.25 mg/m(2) due to these infusional CNS events. The 3-hour infusion schedule studied in GX005 had improved tolerability, and the obatoclax MTD was 20 mg/m(2). One patient in GX005 with relapsed non-Hodgkin's lymphoma achieved partial response of 2 months' duration, and one patient with relapsed non-Hodgkin's lymphoma had stable disease for 18 months.The 1-hour infusion schedule of obatoclax was associated with neuropsychiatric dose-limiting toxicities at relatively low doses (MTD, 1.25 mg/m(2)). The 3-hour i.v. infusion of obatoclax administered once weekly to patients with solid tumors was better tolerated (MTD, 20 mg/m(2)), and evidence of clinical activity was observed.
The Evolutionary Gain of Spliceosomal Introns: Sequence and Phase Preferences
Authors: W.-G. Qiu
Journal: Molecular Biology and Evolution (2004)

Theories regarding the evolution of spliceosomal introns differ in the extent to which the distribution of introns reflects either a formative role in the evolution of protein-coding genes or the adventitious gain of genetic elements. Here, systematic methods are used to assess the causes of the present-day distribution of introns in 10 families of eukaryotic protein-coding genes comprising 1,868 introns in 488 distinct alignment positions. The history of intron evolution inferred using a probabilistic model that allows ancestral inheritance of introns, gain of introns, and loss of introns reveals that the vast majority of introns in these eukaryotic gene families were not inherited from the most recent common ancestral genes, but were gained subsequently. Furthermore, among inferred events of intron gain that meet strict criteria of reliability, the distribution of sites of gain with respect to reading-frame phase shows a 5:3:2 ratio of phases 0, 1 and 2, respectively, and exhibits a nucleotide preference for MAG GT (positions -3 to +2 relative to the site of gain). The nucleotide preferences of intron gain may prove to be the ultimate cause for the phase bias. The phase bias of intron gain is sufficient to account quantitatively for the well-known 5:3:2 bias in phase frequencies among extant introns, a conclusion that holds even when taxonomic heterogeneity in phase patterns is considered. Thus, intron gain accounts for the vast majority of extant introns and for the bias toward phase 0 introns that previously was interpreted as evidence for ancient formative introns.
The role of heat shock proteins in reproduction
Authors: A. Neuer
Journal: Human Reproduction Update (2000)

Heat shock proteins (HSP) were first identified in cells after exposure to elevated temperature. Subsequently HSP have been identified as a critical component of a very complex and highly conserved cellular defence mechanism to preserve cell survival under adverse environmental conditions. HSP are preferentially expressed in response to an array of insults, including hyperthermia, free oxygen radicals, heavy metals, ethanol, amino acid analogues, inflammation and infection. HSP interact with intracellular polypeptides and prevent their denaturation or incorrect assembly. In addition HSP are also involved in several processes essential for cellular function under physiological conditions. HSP production is enhanced during in-vitro embryo culture and they are among the first proteins produced during mammalian embryo growth. The spontaneous expression of HSP as an essential part of embryo development is well documented and the presence or absence of HSP influences various aspects of reproduction in many species. Finally, HSP are immunodominant antigens of numerous microbial pathogens, e.g. Chlamydia trachomatis, which have been recognized as the main cause of tubal infertility. Many couples with fertility problems have had a previous genital tract infection, have become sensitized to microbial HSP, and a prolonged and asymptomatic infection may trigger immunity to microbial HSP epitopes that are also expressed in man. Antibodies to both bacterial and human HSP are present at high titres in sera and hydrosalpinx fluid of many patients undergoing in-vitro fertilization (IVF). In a mouse in-vitro embryo culture model, these antibodies impaired the mouse embryo development at unique developmental stages. Recent studies indicate an association between a previous infection, immunity to HSP and reproductive failure.
Training health workers to educate young women about long acting contraceptive methods reduces pregnancies, study shows
Authors: S. Mayor
Journal: BMJ (2015)

Training healthcare workers to educate young women about long acting reversible contraceptive methods including intrauterine devices (IUDs) and contraceptive implants dramatically reduces the number of unintended pregnancies in women of this age who are seeking contraception services, a US randomised trial has found.1

The study, reported in the Lancet , randomly assigned 20 reproductive health clinics across the United States to receive staff training in counselling and insertion of IUDs and progestin implants, while 20 clinics were randomised to continue providing standard family planning care.

A key part of the evidence based training was teaching healthcare workers to educate women that different …