tbuckley/cabot-search huggingface dataset:
FcγRIIIa-158V/F Polymorphism Influences the Binding of IgG by Natural Killer Cell FcγRIIIa, Independently of the FcγRIIIa-48L/R/H Phenotype
Authors: Harry R. Koene, Marion Kleijer, Johan Algra, Dirk Roos, Albert E.G.Kr. von dem Borne, Masja de Haas
Journal: Blood (1997)
Assessing the Benefit of Radiation Therapy After Breast-Conserving Surgery for Ductal Carcinoma-In-Situ
Authors: James A. Hayman, Mohammed U. Kabeto, Matthew J. Schipper, Jonathan E. Bennett, Frank A. Vicini, Lori J. Pierce
Journal: Journal of Clinical Oncology (2005)

Purpose To assess women's preferences regarding the trade-off between the risks and benefits of treatment with radiation therapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma-in-situ (DCIS). Patients and Methods Utilities were obtained from 120 patients and 210 nonpatients for eight relevant health states using standard gambles. Results Differences in utilities obtained from patient and nonpatient participants between health states were relatively similar. Reduction in the likelihood of local recurrence associated with RT did not result in higher utilities. Utilities for noninvasive recurrence were only lower after initial treatment with RT. Patient and nonpatient participants had the lowest utilities for invasive local recurrence, regardless of initial treatment or manner of salvage therapy. When comparing patient and nonpatient utilities directly, patients had higher utility for being without recurrence after initial RT and lower utility for invasive recurrence salvaged by mastectomy after initial BCS alone. None of the clinical or sociodemographic factors examined explained more than 5% of the variability in the patients' or nonpatients' utilities or their differences. Conclusion The principal benefit associated with adding RT to BCS for DCIS seems to be its ability to reduce invasive recurrences.
Germline single nucleotide polymorphisms associated with response of urothelial carcinoma to platinum-based therapy: the role of the host
Authors: D.J. Gallagher, J. Vijai, R.J. Hamilton, I. Ostrovnaya, G. Iyer, I.R. Garcia-Grossman, P.H. Kim, J.A. Przybylo, S. Alanee, J.C. Riches, A.M. Regazzi, M.I. Milowsky, K. Offit, D.F. Bajorin
Journal: Annals of Oncology (2013)
Phenotype of Infants of Mothers with Gestational Diabetes
Authors: Patrick M. Catalano, Alicia Thomas, Larraine Huston-Presley, Saeid B. Amini
Journal: Diabetes Care (2007)

The phenotype of the infant of the diabetic mother is generally perceived as being macrosomic or large for gestational age. However, not all infants of women with gestational diabetes mellitus (GDM) are macrosomic and, under certain circumstances, because of the interaction of genes and environment, can present as small for gestational age at birth. In contrast, the macrosomic infant presenting with hypoglycemia may not necessarily be the infant of a woman with GDM, but have an underlying metabolic or genetic dysregulation accounting for a similar phenotype. In this review, we will attempt to review the increasing prevalence of obesity in adults, adolescents, and possibly neonates as well. In an effort to better define macrosomia in the infant of the GDM mother, we will review the body composition analyses of infants of GDM mothers. Last, in addition to well-known factors such as maternal glucose control and overall nutrient availability, we will discuss the independent effect of maternal pregravid obesity on fetal adiposity in the infant of the GDM mother. We will be able to develop rational treatment modalities only if we have a better understanding of the various maternal components and factors relating to growth in these infants.

The word “phenotype” has its origins in the Greek language: phainein , to show or appear, and typos , a type or mark. In reviewing the definition of phenotype, it became apparent that the meaning of the word has changed over the past few decades. In the 1960s, the standard definition in a medical dictionary was “the outward visible expression of the hereditary constitution of an organism” (1). This definition appeared well suited to descriptions of the fetus of a diabetic mother at that time. For example, in Pedersen's text, the external appearance of the infant of the mother with diabetes is described …
<i>bcl</i>-2 Transgene Expression Inhibits Apoptosis in the Germinal Center and Reveals Differences in the Selection of Memory B Cells and Bone Marrow Antibody-Forming Cells
Authors: Kenneth G.C. Smith, Amanda Light, Lorraine A. O'Reilly, Soon-Meng Ang, Andreas Strasser, David Tarlinton
Journal: The Journal of Experimental Medicine (2000)

Immunization with T cell-dependent antigens generates long-lived memory B cells and antibody-forming cells (AFCs). Both populations originate in germinal centers and, predominantly, produce antibodies with high affinity for antigen. The means by which germinal center B cells are recruited into these populations remains unclear. We have examined affinity maturation of antigen-specific B cells in mice expressing the cell death inhibitor bcl-2 as a transgene. Such mice had reduced apoptosis in germinal centers and an excessive number of memory B cells with a low frequency of V gene somatic mutation, including those mutations encoding amino acid exchanges known to enhance affinity. Despite the frequency of AFCs being increased in bcl-2-transgenic mice, the fraction secreting high-affinity antibody in the bone marrow at day 42 remained unchanged compared with controls. The inability of BCL-2 to alter selection of bone marrow AFCs is consistent with these cells being selected within the germinal center on the basis of their affinity being above some threshold rather than their survival being due to a selective competition for an antigen-based signal. Continuous competition for antigen does, however, explain formation of the memory compartment.
Methotrexate induced liver cirrhosis
Authors: H. ZACHARIAE, K. KRAGBALLE, H. SøGAARD
Journal: British Journal of Dermatology (1980)

SUMMARY Seven hundred and sixty-four liver biopsies were performed in 328 psoriatics on treatment with methotrexate or being considered for systemic treatment either with methotrexate or with psoralens and long-wave ultraviolet light. The diagnosis of cirrhosis was established histologically in twenty-one patients. Two patients had cirrhosis in their premethotrexate biopsy and were not given methotrexate. The remainder all showed no signs of cirrhosis or fibrosis in their premethotrexate biopsy. The difference between the methotrexate treated psoriatics and the premethotrexate group was highly significant. Among thirty-nine patients treated for more than 5 years, ten developed cirrhosis (25.6%). Almost all patients were on a divided dose intermittent oral dosage schedule. The cumulative dose of methotrexate, when cirrhosis was first found, ranged from 590 to 8105 mg, with an average dosage of 2200 mg. Other factors contributing to cirrhosis in this study seem to be previous treatment with arsenic, a previous intake of alcohol, and lowered renal function. Data on later serial biopsies from fourteen patients, of which eleven continued to receive methotrexate due to very severe psoriasis, seem to indicate that methotrexate induced liver cirrhosis is not of a very aggressive nature. When evaluated blind no progression was found in most of the later biopsies, and a ‘cumulative cirrhosis index’ composed of the combined gradings for fibrosis, assessment of membrana limitans, fibrous destruction and regeneration showed a tendency to decrease. In three patients the latest of the serial biopsies showed no cirrhosis. The observation period on continued methotrexate therapy ranged from 1 to 7 years. None of the patients with cirrhosis differed from the remaining patients on methotrexate in their laboratory results for evaluating liver damage, and apart from transient increases in serum glutamic pyruvic transaminases no abnormalities were found. The data support the necessity of liver biopsies in the control of psoriatics treated with methotrexate. Liver biopsies should be performed at least in all psoriatics in whom a cumulative dosage of methotrexate exceeds 1.5g. The data also indicate that methotrexate can be continued at least for a while in patients where the indication is strong enough, if the dosage is maintained as low as possible and alcohol consumption avoided.
Hope, Truth, and Preparing for Death: Perspectives of Surrogate Decision Makers
Authors: Latifat Apatira
Journal: Annals of Internal Medicine (2008)

Background: Although many physicians worry that openly discussing a poor prognosis will cause patients and families to lose hope, surrogate decision makers' perspectives on this topic are largely unknown. Objective: To determine surrogate decision makers' attitudes toward balancing hope and telling the truth when discussing prognosis. Design: Prospective, mixed-methods cohort study. Setting: 4 intensive care units at the University of California, San Francisco, Medical Center, San Francisco, California. Participants: 179 surrogate decision makers for incapacitated patients at high risk for death. Measurements: One-on-one, semistructured interviews with surrogates were conducted on the patients' 5th day of receiving mechanical ventilation. Constant comparative methods were used to inductively develop a framework to describe participants' responses. Validation methods included multidisciplinary analysis and member checking. Results: Overall, 93% (166 of 179) of surrogates felt that avoiding discussions about prognosis is an unacceptable way to maintain hope. The main explanatory theme was that timely discussion of prognosis is essential to allow family members to prepare emotionally and logistically for the possibility of a patient's death. Other themes that emerged included surrogates' belief that an accurate understanding of a patient's prognosis allows them to better support the patient and each other, a moral aversion to the idea of false hope, the perception that physicians have an obligation to discuss prognosis, and the notion that some surrogates look to physicians primarily for truth and seek hope elsewhere. A few surrogates (6 of 179) felt that physicians should withhold prognostic information because of a belief that discussing death could be emotionally damaging to the family or could negatively affect the patient's health. Limitation: The authors did not longitudinally assess whether early disclosure about prognosis predicts fewer adverse bereavement outcomes. Conclusion: Most surrogates of critically ill patients do not view withholding prognostic information as an acceptable way to maintain hope, largely because timely discussions about prognosis help families begin to prepare emotionally, existentially, and practically for the possibility that a patient will die.
Variation of CD8+ T-lymphocytes around the bronchial internal perimeter in chronic bronchitis
Authors: E. Gamble, W. Burns, J. Zhu, T. Ansari, V. De Rose, J. Kips, N.C. Barnes, P.K. Jeffery
Journal: European Respiratory Journal (2003)

The variation of CD8+ cells has been determined around the internal perimeter of intrapulmonary bronchi in smokers with chronic bronchitis (CB), and the amount of tissue required to confidently estimate the true mean has been calculated. Lung specimens were obtained from 10 smokers with CB. Paraffin sections of intrapulmonary bronchi were immunostained and CD8+ cells counted in the epithelium and subepithelium in up to 10 sequential 1-mm segments around the internal perimeter of each airway. The percentage of counts falling between +/-20% of the final mean was 43.0% for epithelium and 40.9% for subepithelium. In 90% of subjects, the cumulative mean was stable after examination of subepithelial tissue associated with 5 mm of reticular basement membrane. There is considerable variation in the counts of CD8+ cells between adjacent 1-mm airway mucosal segments in chronic bronchitis. In order to achieve a representative count and to maximise statistical power to detect differences between study populations, subepithelial tissue including a minimum of 5 mm of reticular basement membrane length should be examined.
RENAL EFFECTS OF HEMOGLOBIN INFUSIONS IN DOGS IN HEMORRHAGIC SHOCK
Authors: Paul B. Hamilton, Alma Hiller, Donald D. Van Slyke
Journal: The Journal of Experimental Medicine (1947)

The immediate effects of treating hemorrhagic shock in dogs by replacing lost blood with 7 per cent hemoglobin solution were favorable, both on renal function and on general condition. However, subsequent transitory depression of the urea clearance for several days, shown by some of the treated animals, but not by untreated bled controls, indicates sufficient possibility of renal damage by the hemoglobin solution to prevent its recommendation at present as a blood substitute.
Multidrug-resistant, dual-tropic HIV-1 and rapid progression
Authors: Douglas F Nixon, Steven G Deeks, Barbara L Shacklett, Annika C Karlsson
Journal: The Lancet (2005)

In their report of a patient recently infected with a multidrug-resistant HIV-1, Martin Markowitz and colleagues1 state that "treatment options for our patient are limited". Although new antiretroviral drugs are being developed for such patients, it is not clear when we will have the capacity to construct fully suppressive antiretroviral drug regimens.2 To complement these regimens, new immune-based approaches such as cytokine augmentation or immunotherapeutic vaccination may be required.
Association between obesity and asthma in 4-11 year old children in the UK
Authors: J I Figueroa-Munoz, Susan Chinn, Roberto Rona
Journal: Thorax (2001)

<h3>BACKGROUND</h3> There is evidence of a positive association between asthma and obesity in adults and in children. We investigated, in a large sample of English and Scottish primary school children, whether there is a consistent association between fatness and asthma symptoms in Britain. <h3>METHODS</h3> A cross sectional analysis was made of 18 218 children aged 4–11 years who participated in the 1993 or 1994 surveys of the National Study of Health and Growth (NSHG). Children belonged either to English or Scottish representative samples, or an English inner city sample. Asthma attacks in the previous year, occasional wheeze, or persistent wheeze were the symptoms used in the analysis. Body mass index (BMI) and the sum of triceps and subscapular skinfolds converted to standard deviation scores (SDS) were used to assess levels of fatness. <h3>RESULTS</h3> A total of 14 908 children (81.8%) were included in the analysis. In the multiple logistic analysis BMI and asthma (asthma attacks or wheeze) were associated in the representative sample (OR for the comparison of the 10th and 90th centiles of BMI 1.28, 95% CI 1.11 to 1.48), but sum of skinfolds was unrelated to asthma symptoms in most analyses. The association between asthma and BMI was stronger in girls than in boys in the inner city sample, but less convincingly in the representative sample. <h3>CONCLUSIONS</h3> Levels of obesity are associated with asthma symptoms regardless of ethnicity. The association is more consistent for BMI than for sum of skinfolds, partly because obese children are more advanced in their maturation than other children. There is some evidence that, as in adults, the association is stronger in girls than in boys, but only in the multiethnic inner city sample.
Selective Expression of an Interleukin-12 Receptor Component by Human T Helper 1 Cells
Authors: Lars Rogge, Luisella Barberis-Maino, Mauro Biffi, Nadia Passini, David H. Presky, Ueli Gubler, Francesco Sinigaglia
Journal: The Journal of Experimental Medicine (1997)

Interleukin-12 (IL-12), a heterodimeric cytokine produced by activated monocytes and dendritic cells, plays a crucial role in regulating interferon (IFN)-γ production and in the generation of IFN–γ–producing T helper 1 (Th1) cells. Here we show that the IL-12 receptor (IL12R) β2 subunit, a recently cloned binding and signal transducing component of the IL-12R, is expressed on human Th1 but not Th2 clones and is induced during differentiation of human naive cells along the Th1 but not the Th2 pathway. IL-12 and type I but not type II interferons induce expression of the IL-12R β2 chain during in vitro T cell differentiation after antigen receptor triggering. The selective expression and regulation of the IL-12R β2 subunit may help to understand the basis of Th1/Th2 differentiation and may provide therapeutic options for altering the Th1/Th2 balance in several immuno-pathological conditions such as autoimmune diseases and allergies.
There must be a better way
Authors: J. Koffman
Journal: BMJ (1998)

Some years ago I became the custodian for my grandmother's care, a woman with progressive multi-infarct dementia, congestive cardiac failure, and a litany of other medical problems, the common currency of older people. Remarkably, she coped at home, with the help of a sympathetic and pragmatic community psychiatric nurse who visited her regularly. She rarely ventured out of her second floor flat, although by all accounts residential care with regular day care sessions in the local community hospital would have been better for her. But she was stubborn and independent, and among many other more amenable qualities were the reasons we loved her.

Recently my grandmother fell while trying to negotiate her way to the bathroom. I called for her general practitioner to attend, and he organised for her to be admitted to a local teaching hospital. It quickly became clear, while we waited in the accident and emergency department, that her condition was far more serious than I had previously imagined. She had sustained a bad fracture to her right neck of femur (no doubt as a …
Reactivation Versus Clearance of <i>Mycobacterium tuberculosis</i> Using Mammalian Target of Rapamycin Inhibitors in Patients With Cancer Can Be Context Dependent
Authors: Salvador Vale
Journal: Journal of Clinical Oncology (2013)

TO THE EDITOR: In the recent article by Lin et al regarding latent Mycobacterium tuberculosis (MT) infection that transformed into active disease, considered to be the result of suppressed cellular immunity caused by mammalian target of rapamycin (mTOR) inhibitors, the authors state, “In addition to progressive disease and interstitial pneumonitis, tuberculosis is one of the differential diagnoses in patients with lung metastasis treated with mTOR inhibitors.” Nevertheless, recent research shows that the mTOR inhibitors can negatively affect MT by triggering a fundamental process for its survival: autophagy promotion. Accordingly, degradation of intracellular MT by the autophagic process induced by sirolimus (which has an analogous effect to temsirolimus) has been demonstrated. In consequence, these data must be considered before taking the cited postulate at face value. First, patients with cancer have a higher incidence of MT infections compared with controls because of the deterioration of immunity caused by the neoplastic process itself. Aerodigestive tract, lung, and hematologic cancers are especially vulnerable to MT. Conversely, temsirolimus causes immunosuppression through the blockade of proliferation of T and B cells by inhibiting their responses to growth factors, preserving, however, the T-cell regulators subset, with the resultant high forkhead box P3 expression that further attenuates the T-cell cytotoxicity. Moreover, temsirolimus triggers the production of the anti-inflammatory cytokine interleukin-10, thereby promoting MT survival in the host. Indeed, these events favor the advancement of latent MT infection into active disease because of suppressed cellular immunity. As a result, the latent MT may be destroyed at the moment of activation (from the low immunity occurring in cancer) by the protective activity of the mTOR inhibitors. However, if the host has particularly low immunity, the bacteria may overcome the antagonistic autophagy; hence, the immunosuppressant activity of these agents is added to the low immunity caused by cancer itself. Consequently, I suggest that the theory postulated by Lin et al could be rephrased to state: “In addition to progressive disease and interstitial pneumonitis, tuberculosis is one of the differential diagnoses in patients with lung metastasis . . .” with the following addition: “. . . and patients with a recently discovered cancer and with pulmonary lesions that are suggestive of previous MT infection should receive careful surveillance or even preventive treatment in special cases.”
Seventeen in Crohn's disease: less prime than we thought?
Authors: Tim Raine, Arthur Kaser
Journal: Gut (2012)

Over the past decade, population genetic studies and animal models have pointed us to the importance of multiple components of the interleukin (IL)-23 receptor signalling pathway in inflammatory bowel disease (IBD). This receptor is expressed on, and is critical for, the function of the T-helper 17 subset of T cells (Th17), upon which an almost doctrinal focus has been placed, along with, by extension, the prototypic Th17 cytokine, IL-17A, as the pathogenic molecule. However, biology appears to be more complex, as Hueber et al report the surprising failure of the IL17A antibody, secukinumab, in Crohn's disease (CD).1 In their multicentre phase IIa study, 59 patients with established moderate to severe CD were randomised to treatment with secukinumab versus placebo. At a scheduled interim analysis of the data from the first 41 patients, prespecified futility criteria were met, and the trial was therefore prematurely terminated.

A number of aspects of the study design merit further comment. The authors chose an unconventional Bayesian approach to study analysis, reporting as their primary end point the probability of the study drug achieving a reduction in the CD activity index (CDAI) from baseline of ≥50 points compared with placebo. Initial study recruitment was poor, which necessitated a number of amendments to the study protocol, and randomisation caused some imbalances in prior medical and surgical treatment. In an …
In vitro differences between venous and arterial-derived smooth muscle cells: potential modulatory role of decorin
Authors: A WONG, N NILI, B STRAUSS
Journal: Cardiovascular Research (2004)

Objective: We analyzed the phenotypic and functional differences between venous and arterial smooth muscle cells (SMC) and the role of decorin in modulating these differences. Methods and results: SMC were isolated from the jugular veins and carotid arteries of male white New Zealand rabbits. Venous SMC demonstrated increased proliferation (2-fold, p<0.001), migration (1.7-fold, p<0.001), and collagen synthesis (4-fold, p<0.001), with decreased adhesion to collagen and fibronectin (1.2-fold, p<0.01) compared to arterial SMC. Higher levels of gelatinase activity (MMP-2 and MMP-9) and tissue inhibitor of metalloproteinase (TIMP) were also observed in venous SMC. Venous SMC demonstrated increased expression of SMemb and decreased expression of SM1–markers of a dedifferentiated and differentiated phenotype, respectively. Arterial SMC produced increased levels of the inhibitory proteoglycan, decorin, compared to venous SMC. Conditioned medium from arterial SMC (ASMC-CM) significantly decreased DNA synthesis, collagen synthesis, and gelatinase activity in venous SMC. Removal of decorin from ASMC-CM by immunoprecipitation significantly reversed the inhibitory effects of ASMC-CM on venous SMC proliferation and collagen synthesis but did not affect gelatinase activities. Conclusion: Venous SMC are more dedifferentiated and demonstrate increased proliferative and synthetic capacity than arterial SMC. Differential decorin expression between arterial and venous SMC contributes to these differences in biologic behavior. Venous SMC properties may contribute to accelerated atherosclerosis in venous bypass grafts.
Aldosterone and parathyroid hormone interactions as mediators of metabolic and cardiovascular disease
Authors: Andreas Tomaschitz, Eberhard Ritz, Burkert Pieske, Jutta Rus-Machan, Katharina Kienreich, Nicolas Verheyen, Martin Gaksch, Martin Grübler, Astrid Fahrleitner-Pammer, Peter Mrak, Hermann Toplak, Elisabeth Kraigher-Krainer, Winfried März, Stefan Pilz
Journal: Metabolism (2013)