tbuckley/cabot-search huggingface dataset:
Single dose of anti-D immunoglobulin for antenatal prophylaxis is smaller in the Netherlands than in the United Kingdom
Authors: B. van Dijk
Journal: BMJ (1998)

Protecting children from armed conflictChildren affected by war must not be stigmatised as permanently damagedEditor-Southall and Abbasi quote Unicef when they state that the psychological consequences of armed conflict on children are so great that they can rarely be repaired. 1Unicef indeed says that "time does not heal trauma," but there is no sound empirical basis for a generalisation that risks stigmatising whole populations of children affected by war as sick or permanently damaged.Even child survivors of Auschwitz did not turn out like this as a general rule, and there are no published studies of children from non-Western war zones to support such a conlusion.Unicef and other agencies need to review such claims and costly interventions based on them; the claims owe more to prevailing sociocultural assumptions in the West than anything else.Over the past 50 years psychological explanations for life events and the medicalisation of distress have grown hugely.Because many people believe, for example, that rape or other criminal violence, childhood abuse, or even persistent bullying at school is an experience that may have lifelong psychological effects it seems unthinkable that war and atrocity should not do this to almost everyone exposed to them.Constructions of "trauma" deployed in the health field are increasingly expansive and undiscriminating. 2 No one wants to play down what children may suffer, or that war may produce clear psychological dysfunction in some (a minority).But it is not to their mental worlds but to their social worlds that survivors direct their attention, and humanitarian agencies should follow suit.The literature of both anthropology and mental health (in the case of mental health, starting with a classic study by Freud and Burlingham 3 ) shows the positive impact of family and community in buffering the short and longer term effects of war.The concept of child trauma is currently fashionable.But it is the social, cultural, and economic rebuilding of worlds shattered by war (including valued institutions such as schools), allied to urgent issues of equity and justice, which will determine the future wellbeing of several million child survivors worldwide. 4For those for whom this does not happen war may indeed mean a life sentence, but this is not trauma.
HYPOCATALASEMIA: A NEW GENETIC CARRIER STATE*
Authors: Shigeo Takahara, Howard B. Hamilton, James V. Neel, Thomas Y. Kobara, Yoshio Ogura, Edwin T. Nishimura
Journal: Journal of Clinical Investigation (1960)

Acatalasemia, a rare congenital abnormality characterized by an apparent lack of the enzyme catalase, was first discovered by Takahara and Miyamoto in 1947 (1, 2).The lack of catalase activity in this disease was initially noted in whole blood, but subsequent studies of the tissues of other organs such as the nasal and oral cavities, the pharynx, bone marrow and liver have revealed a similar absence of activity for this enzyme (3-5).Since the initial description of this disease, 38 cases in 17 families have been found and reported in Japan up to April 1959 (6-17); at this writing no reports of acatalasemia have appeared from any other countries of the world.Shortly after the discovery of acatalasemia it became apparent that the condition probably re- sulted from homozygosity for a recessive gene (18).Because of the widespread interest in the biochemical identification of genetic carrier states, we undertook a study of persons presumed to be
Impaired immunity in patients with inflammatory bowel disease and hyposplenism: the response to intravenous phi X174.
Authors: F P Ryan, J V Jones, J K Wright, C D Holdsworth
Journal: Gut (1981)

Eight patients with inflammatory bowel disease were tested for their ability to mount a serological response to the intravenous particulate antigen phi X174. Seven patients had extensive ulcerative colitis and one patient extensive Crohn9s colitis, four having severe hyposplenism and four normal splenic function. The antibody response to phi X174 was grossly impaired in those with hyposplenism.
Spondylitis erosiva: report on 9 patients.
Authors: I Jajić, Z Furst, B Vuksic
Journal: Annals of the Rheumatic Diseases (1982)

Nine patients (5 male and 4 female) are described with mild pain in the lumbar and thoracolumbar spine, early morning pain, morning stiffness, and moderately reduced mobility of the spine. Initial x-ray examination of the spine revealed sclerosis of one or several vertebral bodies and erosions in various parts of the vertebral bodies. In the further course of the disease squaring, sacroiliitis, and arthritis of the apophyseal joints was found. Seven of the 9 patients had the histocompatability antigen HLA B27. On the basis of these observations it is considered that 7 of these 9 patients had ankylosing spondylitis, the erosive lesions of the vertebral bodies being the first visible signs of the disease.
Migration Patterns and Breast Cancer Risk in Asian-American Women
Authors: R. G. Ziegler, R. N. Hoover, M. C. Pike, A. Hildesheim, A. M. Y. Nomura, D. W. West, A. H. Wu-Williams, L. N. Kolonel, P. L. Horn-Ross, J. F. Rosenthal, M. B. Hyer
Journal: JNCI Journal of the National Cancer Institute (1993)

Breast cancer incidence rates have historically been 4-7 times higher in the United States than in China or Japan, although the reasons remain elusive. When Chinese, Japanese, or Filipino women migrate to the United States, breast cancer risk rises over several generations and approaches that among U.S. Whites.Our objective was to quantify breast cancer risks associated with the various migration patterns of Asian-American women.A population-based, case-control study of breast cancer among women of Chinese, Japanese, and Filipino ethnicities, aged 20-55 years, was conducted during 1983-1987 in San Francisco-Oakland, California, Los Angeles, California, and Oahu, Hawaii. We successfully interviewed 597 case subjects (70% of those eligible) and 966 control subjects (75%).A sixfold gradient in breast cancer risk by migration patterns was observed. Asian-American women born in the West had a breast cancer risk 60% higher than Asian-American women born in the East. Among those born in the West, risk was determined by whether their grandparents, especially grandmothers, were born in the East or the West. Asian-American women with three or four grandparents born in the West had a risk 50% higher than those with all grandparents born in the East. Among the Asian-American women born in the East, breast cancer risk was determined by whether their communities prior to migration were rural or urban and by the number of years subsequently lived in the West. Migrants from urban areas had a risk 30% higher than migrants from rural areas. Migrants who had lived in the West for a decade or longer had a risk 80% higher than more recent migrants. Risk was unrelated to age at migration for women migrating at ages less than 36 years. Ethnic-specific incidence rates of breast cancer in the migrating generation were clearly elevated above those in the countries of origin, while rates in Asian-Americans born in the West approximated the U.S. White rate.Exposure to Western lifestyles had a substantial impact on breast cancer risk in Asian migrants to the United States during their lifetime. There was no direct evidence of an especially susceptible period, during either menarche or early reproductive life.Because heterogeneity in breast cancer risk in these ethnic populations is similar to that in international comparisons and because analytic epidemiologic studies offer the opportunity to disentangle correlated exposures, this study should provide new insights into the etiology of breast cancer.
A Long-Term Evolutionary Pressure on the Amount of Noncoding DNA
Authors: Carole Knibbe, Antoine Coulon, Olivier Mazet, Jean-Michel Fayard, Guillaume Beslon
Journal: Molecular Biology and Evolution (2007)

A significant part of eukaryotic noncoding DNA is viewed as the passive result of mutational processes, such as the proliferation of mobile elements. However, sequences lacking an immediate utility can nonetheless play a major role in the long-term evolvability of a lineage, for instance by promoting genomic rearrangements. They could thus be subject to an indirect selection. Yet, such a long-term effect is difficult to isolate either in vivo or in vitro. Here, by performing in silico experimental evolution, we demonstrate that, under low mutation rates, the indirect selection of variability promotes the accumulation of noncoding sequences: Even in the absence of self-replicating elements and mutational bias, noncoding sequences constituted an important fraction of the evolved genome because the indirectly selected genomes were those that were variable enough to discover beneficial mutations. On the other hand, high mutation rates lead to compact genomes, much like the viral ones, although no selective cost of genome size was applied: The indirectly selected genomes were those that were small enough for the genetic information to be reliably transmitted. Thus, the spontaneous evolution of the amount of noncoding DNA strongly depends on the mutation rate. Our results suggest the existence of an additional pressure on the amount of noncoding DNA, namely the indirect selection of an appropriate trade-off between the fidelity of the transmission of the genetic information and the exploration of the mutational neighborhood. Interestingly, this trade-off resulted robustly in the accumulation of noncoding DNA so that the best individual leaves one offspring without mutation (or only neutral ones) per generation.
Male infertility and environmental exposure to lead and cadmium
Authors: S. Benoff
Journal: Human Reproduction Update (2000)

Humans are exposed occupationally and environmentally to metal aerosols including lead (Pb2+) and cadmium (Cd2+). These toxicants accumulate in male reproductive organs. Epidemiological studies have been equivocal about effects of Pb2+ and Cd2+ on hormone concentrations, male fertility and sperm parameters. Comparison of Pb2+ and Cd2+ concentrations in fertile and infertile men are problematic. Problem areas include failure to control confounding variables, but genetic polymorphisms as in somatic diseases may modulate Pb2+ and Cd2+ damage. Multiple calcium (Ca2+) and potassium (K+) channel isoforms have been identified in human testes and spermatozoa. These Ca2+ and K+ channels are involved in early events of acrosome reactions. Ca2+ channel are susceptible to Cd2+ poisoning and K+ channels to Pb2+. These channels offer entry paths for metallic toxicants into mature spermatozoa. Ion channel polymorphisms may cause differential sensitivities to Cd2+ and Pb2+, explaining in part prospective blinded studies showing high Cd2+ in varicocele-related human infertility and high Pb2+ in unexplained infertility. In both forms of male infertility the ability to undergo an acrosome reaction decreases. Reverse transcriptase-polymerase chain reaction assays for Ca2+ and K+ channel isoforms may identify susceptibility subgroups with lower resistance to environmental exposures.
Lactoferrin: Molecular Structure and Biological Function
Authors: B. Lönnerdal, S. Iyer
Journal: Annual Review of Nutrition (1995)

Lactoferrin is an 80-kDa, iron-binding glycoprotein present in milk and, to a lesser extent, in exocrine fluids such as bile and tears. It consists of a single-chain polypeptide with two gobular lobes and is relatively resistant to proteolysis. The complete cDNAs for lactoferrin from human milk, neutrophils, and bovine milk have been reported, and recombinant proteins have been produced. Owing to its iron-binding properties, lactoferrin has been proposed to play a role in iron uptake by the intestinal mucosa and to act as a bacteriostatic agent by withholding iron from iron-requiring bacteria. Its presence in neutrophils and its release during inflammation suggest that lactoferrin is also involved in phagocytic killing and immune responses. Additionally, lactoferrin may function in ways not related to iron-binding, e.g. as a growth factor and as a bactericidal agent. This review attempts to evaluate these proposed functions and their biological significance in more detail.
Effect of Beta-Adrenergic Stimulation on Myocardial Adenine Nucleotide Metabolism
Authors: HEINZ-GERD ZIMMER, ECKEHART GERLACH
Journal: Circulation Research (1974)

The effects of isoproterenol, propranolol, and compound D600 (α-isopropyl-α-[( N -methyl- N -homoveratryl)-γ-aminopropyl1-3, 4, 5-trimethoxyphenylacetonitrile) on myocardial adenine nucleotide metabolism were studied in rat hearts in situ. Isoproterenol in doses between 0.1 and 25 mg/kg induced an increase in heart rate concomitant with a significant acceleration in the de novo synthesis of adenine nucleotides (ATP, ADP, and AMP) and a diminution in their concentration. The effects of isoproterenol were antagonized by propranolol (1 and 50 mg/kg), which alone caused a reduction in the de novo synthesis of adenine nucleotides without inducing a change in their concentration. Compound D600 (10 mg/kg) brought about a slight elevation in the concentration of adenine nucleotides but did not influence the rate of de novo synthesis. The isoproterenol-induced diminution in adenine nucleotide concentration was prevented by D600; under these conditions, the acceleration of de novo synthesis was attenuated. These findings indicate that de novo synthesis of myocardial adenine nucleotides in the normal and the isoproterenol-stimulated heart is regulated not only by a feedback mechanism dependent on the concentration of adenine nucleotides but also by β-receptor-mediated alterations in carbohydrate metabolism which can cause changes in the size of the available pool of 5-phosphoribosyl-1-pyrophosphate.
Adenovirus-Mediated Gene Transfer of a Secreted Form of Human Macrophage Scavenger Receptor Inhibits Modified Low-Density Lipoprotein Degradation and Foam-Cell Formation in Macrophages
Authors: Johanna Laukkanen, Pauliina Lehtolainen, Peter J. Gough, David R. Greaves, Siamon Gordon, Seppo Ylä-Herttuala
Journal: Circulation (2000)

Macrophage scavenger receptors (MSRs) play an important role in the pathogenesis of atherosclerosis. Therefore, local modulation of MSR activity could have a beneficial effect on atherogenesis.We cloned a secreted "decoy" MSR (sMSR) that contains an extracellular portion of the human MSR type AI and constructed an adenoviral vector that directs high-level expression of sMSR in macrophages under the control of the human CD68 promoter. Expression of the sMSR protein inhibited the degradation of (125)I-labeled acetylated LDL and oxidized LDL by murine macrophages up to 90%. sMSRs also reduced acetylated LDL degradation in MSR knockout mouse peritoneal macrophages by 60% to 80%, which suggests that the decoy construct can compete for the uptake mediated via other related scavenger receptors. In addition, sMSRs inhibited foam-cell formation in murine macrophages in the presence of cytochalasin D. The mechanism of inhibition is through ligand binding to the sMSRs, which prevents the ligand binding to MSRs on cell membranes.The demonstration that recombinant adenovirus-mediated gene transfer of decoy sMSRs can block foam-cell formation suggests a possible new strategy for gene therapy of atherosclerosis and for the treatment of lipid accumulation after arterial manipulations.
Physician-Identified Factors Affecting Patient Participation in Reaching Treatment Decisions
Authors: Heather L. Shepherd, Martin H.N. Tattersall, Phyllis N. Butow
Journal: Journal of Clinical Oncology (2008)

Cancer physicians report high comfort with shared decision making but a lower frequency of using this approach in practice. Information regarding physicians' perceptions of what helps and what hinders patient involvement in decision making may facilitate understanding of this discrepancy.We surveyed 604 Australian cancer physicians treating breast, colorectal, gynecologic, hematologic, or urologic cancer to investigate barriers and facilitators to reaching treatment decisions with their patients and their support of strategies to encourage patient involvement and reflection on treatment options. Factor analysis and regression analyses were used to investigate relationships between variables and identify predictors of greater reporting of barriers to sharing treatment decisions with patients.Insufficient information at the first consultation (28.9%) and insufficient time (28.4%) were the most frequently reported barriers to reaching treatment decisions with patients. Multivariate analysis revealed that less experienced physicians more commonly reported system barriers (P = .00). Patients trusting their physician and being accompanied at the consultation were most helpful to reaching a treatment decision. Providing written information about treatment options, making a further appointment to reach a decision, encouraging the patient to speak with their family physician and treatment team, and the presence of a third person during the consultation were felt to encourage involvement and reflection on treatment decisions.Cancer physicians experience difficulties when reaching treatment decisions with their patients. Interventions and strategies that physicians support are required to enhance patient involvement in reaching a treatment decision.
Phase II Study of Sunitinib in Patients With Metastatic Urothelial Cancer
Authors: David J. Gallagher, Matthew I. Milowsky, Scott R. Gerst, Nicole Ishill, Jamie Riches, Ashley Regazzi, Mary G. Boyle, Alisa Trout, Anne-Marie Flaherty, Dean F. Bajorin
Journal: Journal of Clinical Oncology (2010)

No standard therapy exists for metastatic urothelial cancer (UC) that has progressed after initial chemotherapy. This trial was designed to assess the efficacy and tolerability of sunitinib in patients with advanced, previously treated UC.In this phase II trial, 77 patients received sunitinib between September 2006 and January 2009 on one of two schedules (50 mg per day for 4 weeks on and 2 weeks off [cohort A], 37.5 mg per day continuously [cohort B]), using a Simon 2 stage design in each cohort separately.A partial response was seen in three of 45 patients (95% CI, 1% to 18%) in cohort A, and in one of 32 patients (95% CI, 0% to 16%) in cohort B. Clinical regression or stable disease was achieved in 33 of 77 patients (43%). Tumor regression lasted between 0.6 and 23.4 months with 29% of patients achieving response lasting longer than 3 months. The progression-free survival (2.4 v 2.3 months; P = .4) and overall survival (7.1 v 6.0 months; P = .4) were similar in both cohorts. There was one treatment-related death, and 47 patients (33 cohort A, 24 cohort B) experienced grade 3 or 4 toxicity.Sunitinib did not achieve the predetermined threshold of >or= 20% activity defined by Response Evaluation Criteria in Solid Tumors. However, antitumor responses were observed, identifying the vascular endothelial growth factor axis as a viable pathway for UC treatment. The reported clinical benefit in previously treated patients warrants further investigation in a disease for which there is no US Food and Drug Administration-approved treatment.
Principles for international registration of protocol information and results from human trials of health related interventions: Ottawa statement (part 1)
Authors: Karmela Krleža-Jerić, An-Wen Chan, Kay Dickersin, Ida Sim, Jeremy Grimshaw, Christian Gluud
Journal: BMJ (2005)

Registering of trials is essential to make sure all results are publicly available and that ethical obligations to participants are met Recent evidence of selective reporting of results has eroded public and academic confidence in publications of clinical trials, leading to renewed calls for trial registration.1–5 The dangers of non-disclosure of trial results, although described for years, sparked an international furore last spring after the publication of two systematic reviews on the effects of selective serotonin reuptake inhibitors for childhood depression.1 6 Subsequent legal proceedings7 and policy statements by journal editors,8 9 medical associations,10 and industry11 have recognised the importance of trial registration. The rationale for registering trials is well known (box 1).12 13 Most importantly, the contribution to social good that justifies research on human participants is not realised when resulting knowledge remains invisible. As an interested and neutral party that has been registering the trials that it funds,14 the Canadian Institutes of Health Research hosted an open meeting on 4 October 2004 in Ottawa, Canada, to foster international consensus on trial registration. The resulting Ottawa statement aims to establish internationally recognised principles for registration (box 2). The full statement is on bmj.com, but here we highlight and discuss some of the key principles. A statement on how to implement these principles (part 2) is still in development. The mandatory registration of all trials has three components: ### Box 1: Rationale for registration of clinical trials #### Ethical
Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies
Authors: John F. DiJoseph, Douglas C. Armellino, Erwin R. Boghaert, Kiran Khandke, Maureen M. Dougher, Latha Sridharan, Arthur Kunz, Philip R. Hamann, Boris Gorovits, Chandrasekhar Udata, Justin K. Moran, Andrew G. Popplewell, Sue Stephens, Philip Frost, Nitin K. Damle
Journal: Blood (2003)
Distinct Ras Effector Pathways Are Involved in FcεR1 Regulation of the Transcriptional Activity of Elk-1 and NFAT in Mast Cells
Authors: Helen Turner, Doreen A. Cantrell
Journal: The Journal of Experimental Medicine (1997)

Activation of Ras GTPases is a conserved feature of antigen receptor signaling, including FcεR1 activation of mast cells. Antigenic cross-linking of the FcεR1 on mast cells results in secretion of allergic mediators and induction of immediate early and cytokine genes. Here we examine the role of Ras in coupling the FcεR1 to transcriptional regulation. The transcription factors Elk-1, an immediate early gene regulator and the nuclear factor of activated T cells (NFAT), in the context of the IL-4 gene, are identified as Ras targets in mast cells. Ras mediates diverse effects via its diverse effector pathways, which may include other members of the Ras GTPase family such as RhoA and Rac-1. We observe that Elk-1 and NFAT are targeted by distinct Ras effector pathways in mast cells. Activation of the “classical” Ras/Raf-1/MEK/ ERK cascade is necessary and sufficient for FcεR1 induction of Elk-1. Ras function is required, but not sufficient for FcεR1 induction of NFAT. However, activation or inhibition of Ras markedly shifts the antigen dose-response for FcεR1 induction of NFAT. The effector pathway for Ras activation of NFAT is not Raf-1/MEK. We identify that the Rac-1 GTPase is critical in FcεR1 regulation of NFAT, acting either in parallel with or as an effector of Ras. These data place Ras in a crucial position in mast cells, regulating disparate nuclear targets. Moreover, we identify that two GTPases, Ras and Rac-1, are important regulators of NFAT, and therefore of cytokine expression in mast cells.