tbuckley/cabot-search huggingface dataset:
Impaired Dihydrotestosterone Catabolism in Human Prostate Cancer: Critical Role of AKR1C2 as a Pre-Receptor Regulator of Androgen Receptor Signaling
Authors: Qing Ji, Lilly Chang, Frank Z. Stanczyk, Murad Ookhtens, Andy Sherrod, Andrew Stolz
Journal: Cancer Research (2007)

Abstract We previously reported the selective loss of AKR1C2 and AKR1C1 in prostate cancers compared with their expression in paired benign tissues. We now report that dihydrotestosterone (DHT) levels are significantly greater in prostate cancer tumors compared with their paired benign tissues. Decreased catabolism seems to account for the increased DHT levels as expression of AKR1C2 and SRD5A2 was reduced in these tumors compared with their paired benign tissues. After 4 h of incubation with benign tissue samples, 3H-DHT was predominately catabolized to the 5α-androstane-3α,17β-diol metabolite. Reduced capacity to metabolize DHT was observed in tumor samples from four of five freshly isolated pairs of tissue samples, which paralleled loss of AKR1C2 and AKR1C1 expression. LAPC-4 cells transiently transfected with AKR1C1 and AKR1C2, but not AKR1C3, were able to significantly inhibit a dose-dependent, DHT-stimulated proliferation, which was associated with a significant reduction in the concentration of DHT remaining in the media. R1881-stimulated proliferation was equivalent in all transfected cells, showing that metabolism of DHT was responsible for the inhibition of proliferation. PC-3 cells overexpressing AKR1C2 and, to a lesser extent, AKR1C1 were able to significantly inhibit DHT-dependent androgen receptor reporter activity, which was abrogated by increasing DHT levels. We speculate that selective loss of AKR1C2 in prostate cancer promotes clonal expansion of tumor cells by enhancement of androgen-dependent cellular proliferation by reducing DHT metabolism. [Cancer Res 2007;67(3):1361–9]
Autologous Bone Marrow Transplantation as Compared with Salvage Chemotherapy in Relapses of Chemotherapy-Sensitive Non-Hodgkin's Lymphoma
Authors: Thierry Philip, Cesare Guglielmi, Anton Hagenbeek, Renier Somers, Hans Van Der Lelie, Dominique Bron, Pieter Sonneveld, Christian Gisselbrecht, Jean-Yves Cahn, Jean-Luc Harousseau, Bertrand Coiffier, Pierre Biron, Franco Mandelli, Franck Chauvin
Journal: New England Journal of Medicine (1995)

High-dose chemotherapy followed by autologous bone marrow transplantation is a therapeutic option for patients with chemotherapy-sensitive non-Hodgkin's lymphoma who have relapses. In this report we describe a prospective randomized study of such treatment.
Momentum to tackle non-communicable diseases must be maintained
Authors: M. Limb
Journal: BMJ (2012)

World bodies and national governments should act urgently and work harder to engage the public in a global fight against non-communicable diseases, a conference of experts has heard.

Specialists from the fields of medicine, public health, policy, research, and international development said that more energy should be put into the cause and called for widespread efforts to mobilise support.

Richard Smith, director of the UnitedHealth chronic disease initiative and a former editor of the BMJ , said that the problem of non-communicable diseases would get worse without action, particularly in low and middle income countries.

“Deaths from chronic diseases are displacing deaths from infectious diseases, even in rural Bangladesh,” he said. “We have to find ways to raise public consciousness. The response must be all of government and all of …
XII. Clinical Laboratories Become Important, 1870-1900
Authors: Lester S. King
Journal: JAMA (1983)

A clinical laboratory examines some part of the living patient—his excreta or blood or secretions—to help the physicians reach a diagnosis or provide a better treatment. The oldest example of this, going far back into antiquity, is uroscopy. As the name indicates, in this examination the physician did not manipulate the urine but merely looked at it. Certain appearances allegedly correlated with certain clinical states. The principle involved—that the characteristics of the urine provided a<i>sign</i>of what was going on within the body—was sound, even though the coefficient of error was enormous. For centuries, physicians studied the urine with various methods, attempting to draw conclusions that would remain valid. Hermann Boerhaave (1668-1738) for example, early in the 18th century, tried to determine whether urine contained "blood serum." He collected a cask of urine whose weight, he said, he reduced by evaporation from 100 lb to 1 lb. But, he
Targeting the MHC class II pathway of antigen presentation enhances immunogenicity and safety of allergen immunotherapy
Authors: J. M. Martínez‐Gómez, P. Johansen, H. Rose, M. Steiner, G. Senti, C. Rhyner, R. Crameri, T. M. Kündig
Journal: Allergy (2008)

Background: Current s.c. allergen‐specific immunotherapy (SIT) leads to amelioration of IgE‐mediated allergy, but it requires numerous allergen injections over several years and is frequently associated with severe side‐effects. The aim of this study was to test whether modified recombinant allergens can improve therapeutic efficacy in SIT while reducing allergic side‐effects. Methods: The major cat allergen Fel d 1 was fused to a TAT‐derived protein translocation domain and to a truncated invariant chain for targeting the MHC class II pathway (MAT‐Fel d 1). The immunogenicity was evaluated in mice, while potential safety issues were assessed by cellular antigen stimulation test (CAST) using basophils from cat‐dander‐allergic patients. Results: MAT‐Fel d 1 enhanced induction of Fel d 1‐specific IgG2a antibody responses as well as the secretion of IFN‐γ and IL‐2 from T cells. Subcutaneous allergen‐specific immunotherapy of mice using the modified Fel d 1 provided stronger protection against anaphylaxis than SIT with unmodified Fel d 1, and MAT‐Fel d 1 caused less degranulation of human basophils than native Fel d 1. Conclusion: MAT‐Fel d 1 allergen enhanced protective antibody and Th1 responses in mice, while reducing human basophil degranulation. Immunotherapy using MAT‐Fel d 1 allergen therefore has the potential to enhance SIT efficacy and safety, thus, shortening SIT. This should increase patient compliance and lower treatment costs.
Treatment of Cervical Spine Dislocation
Authors: Maurice W. Nicholson
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Dislocations and fractures of the cervical spine can be treated in a more efficatious manner than that outlined in the FRACTURE OF THE MONTH (<b>218</b>:1288, 1971). Approximately 14 years ago, Cloward started fusing this type of fracture dislocation by the anterior route, and for the past six years I have done so in the same manner. By putting these patients in traction immediately, using Crutchfield tongs and 20 lb of weight, the neck can be stabilized, and on occasion the dislocation can be reduced. Later the patient is operated on by the anterior approach, using the method as described previously by Cloward. After exposure of the dislocation, the torn disk can be removed, and using the vertebral spreader and increased amounts of traction, the spine can be put into proper alignment. Then a bone dowel is placed in the interspace and the spine is stabilized. This
Clinical Applications of Fish Oils
Authors: Jack Zeev Yetiv
Journal: JAMA (1988)

Fish oil supplements are currently being nationally advertised, and many physicians are being queried about their clinical utility. Epidemiologic studies reveal a low incidence of cardiovascular disease in people, such as the Eskimos, who eat large amounts of seafood. Cardiovascular health may be improved because fish and fish oil supplements lower plasma lipid levels (especially triglycerides), inhibit platelet aggregation, and may decrease blood pressure and viscosity and increase high-density lipoprotein (HDL) levels. Preliminary observations also suggest a potential future role for fish oils in the treatment of some autoimmune diseases, such as atopic dermatitis, psoriasis, and rheumatoid arthritis. Patients with serum triglyceride levels greater than 5.64 mmol/L and/or cholesterol levels greater than 7.75 mmol/L refractory to dietary management may benefit from a medically supervised trial of fish oil supplements. Data currently available are insufficient to recommend fish oil supplements for the general public, or for patients with other diseases, and side effects must also be considered. These include occasional adverse lipid changes, potential for bleeding and vitamin E deficiency, and, with some preparations, vitamin A and D toxicity.
Retirement: "Second Wind"
Authors: Burgess L. Gordon
Journal: JAMA (1975)

To the Editor.—  The editorial on retirement, by Robert H. Moser, MD, (230:1311, 1974) is timely, factual, and brilliant. The position of the American Medical Association is clearly stated, namely that the nation's social policy should ensure that the older worker has the opportunity to continue productive employment as long as he wishes and is able to maintain a satisfactory level of efficiency.  The AMA declaration is strongly supported by an amicus curiae brief of Bernard D. Hirsh, JD, General Counsel for the AMA. The case in point has to do with a challenge to the constitutionality of the Federal Employee Mandatory Requirement Law, 5 USC8335.  Difficulties of retirement may be rooted in laxity or misconceptions at employment time—to become the forerunners of compromise, expediency, cost-saving measures, and hurried ambition. In a gloomy light, some believe that retirees live too long for their own good and posterity's—yet, conversely there is uncertainty
Effectiveness of a Nonselective ET <sub>A/B</sub> and a Selective ET <sub>A</sub> Antagonist in Rats With Monocrotaline-Induced Pulmonary Hypertension
Authors: Jean-François Jasmin, Martin Lucas, Peter Cernacek, Jocelyn Dupuis
Journal: Circulation (2001)

Background —Both nonselective ET A/B receptor and selective ET A receptor antagonists can reduce pulmonary hypertension (PH) and right ventricular hypertrophy (RVH) in various animal models. Depending on their net effects after blockade of endothelial and smooth muscle ET B receptors, nonselective ET A/B antagonists could be more or less effective than selective ET A antagonists. Methods and Results —Two weeks after injection of saline or 60 mg/kg monocrotaline (MCT), rats received 50 mg · kg −1 · d −1 of a selective ( LU135252 ) or nonselective (BSF420627) antagonist for 3 weeks. This resulted in 4 groups: control (n=15), MCT (n=60), MCT+ET A (n=39), and MCT+ET A/B (n=40). Five-week survival was 35% in the MCT group; this was increased to 56% in the MCT+ET A group ( P =0.10) and to 67% in the MCT+ET A/B group ( P =0.0015). Drug administration was stopped 48 hours before hemodynamic measurements to evaluate the chronic effects of therapy: PH in the MCT group (RV systolic pressure 87±1 mm Hg) was improved similarly in both MCT+ET A and MCT+ET A/B groups (72±3 and 70±3 mm Hg, respectively, P &lt;0.05). Severe RVH in the MCT group (RV/left ventricle+septum weight ratio 73±1%) was not affected by the selective antagonist (70±2%) but was reduced to 54±2% in the MCT+ET A/B group ( P &lt;0.01). Pulmonary resistive properties, assessed from isolated lung pressure-flow relationships, were improved similarly in survivors from both treated groups. Conclusions —Both the nonselective ET A/B antagonist BSF420627 and the selective ET A antagonist LU135252 are effective in this model of PH. Similar direct comparative studies in other models of PH and with various dosage regimens are warranted to define the optimal pharmacological approach of PH when ET receptor antagonists are used.
754-5 A Multi-Centre Double Blind Crossover Comparison of Disopyramide, Atenolol, and Placebo for Symptomatic Paroxysmal Atrial Fibrillation
Authors: Francis D. Murgatroyd, Dympna M. O’Farrell, John P. Foran, Stephen J. Kelly, David E. Ward, A. John Camm
Journal: Journal of the American College of Cardiology (1995)
Postpsychiatry: a new direction for mental health
Authors: P. Bracken
Journal: BMJ (2001)

<h3>Objectives</h3> To investigate the effects and mechanisms of action of high-density lipoproteins (HDL) in monosodium urate (MSU) crystal-induced inflammation —that is, gouty inflammation, in vivo. <h3>Methods</h3> Air pouches raised on the backs of mice were injected with MSU crystals or tumour necrosis factor (TNF) in the presence or absence of HDL and/or interleukin (IL)-1 receptor antagonist (IL-1Ra) for 3 h. Leucocyte count and neutrophil percentage in pouch fluids were measured using a haemocytometer and May–Grünwald–Giemsa staining. The cytokine production and expression in the pouch were measured by ELISA and quantitative RT-PCR. <h3>Results</h3> MSU crystals induced leucocyte infiltration, mostly neutrophils, and the release of IL-1β, IL-6, chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-C motif) ligand 2 (CCL2) and IL-1Ra in pouch fluids. TNF remained under the detection limit. MSU crystals triggered IL-1β, IL-6 and CXCL1 expression in both pouch exudates and membranes, whereas CCL2 and TNF mRNA were not modulated. The co-injection of MSU crystals and HDL inhibited leucocyte influx by 59% and neutrophil infiltration by 83% and, in turn, both protein and mRNA levels of all assessed proinflammatory cytokines were reduced, but not those of IL-1Ra. Similar results were obtained when mice were injected with MSU crystals pretreated with HDL or TNF instead of crystals. When HDL and IL-1Ra were added together they displayed additional inhibition, suggesting different mechanisms of action. <h3>Conclusions</h3> This study demonstrated that HDL may represent an important factor in the modulation of gouty inflammation by acting on both tissue and infiltrating cells —that is, synovial tissue and synovial fluid cells. HDL display anti-inflammatory activity, in part, by interacting with crystals but also by directly acting on cells.
Abstract 4330: Endometrial hyperplasia resulting from myeloid-specific targeting of the tumor suppressor APC
Authors: Susan M. Kitchen-Goosen, Art Alberts
Journal: Cancer Research (2011)

Abstract The Adenomatous polyposis coli (APC1) tumor suppressor is a multi-function protein with a central role in Wnt-regulated cell growth and differentiation. Additionally, APC functions to modulate microtubule and microfilament dynamics to establish polarity in epithelia during directed cell migration and asymmetric cell division. APC frequently collaborates with the canonical Diaphanous-related formin, mDia1 (DIAPH1), which also binds microfilaments and microtubules to modulate cytoskeletal dynamics. APC1 and DIAPH1 are genetically linked on chromosome 5q in a region frequently disrupted in myeloproliferative neoplasms (MPNs). mDia1 knockout mice develop an age-dependent outgrowth of myeloid-lineage cells. The physical and functional linkage of APC and mDia1 as 5q tumor suppressors and in cytoskeletal remodeling led us to explore the role of APC in tumor suppression in myeloid-derived cell lineages affected by mDia1 knockout. To test this hypothesis in a genetic model, we created a mouse in which APC was knocked out in myeloid lineage cells by breeding the Apc-flox mice with mice expressing Cre recombinase under the control of lysozyme M (LyzsM) gene promoter. The resulting phenotype was unexpected and 100% penetrant: Female mice developed cystic endometrial hyperplasia and were unable to sustain pregnancy. Embryo implantation occurred, but embryos were resorbed mid-gestation irrespective of progeny genotype. Two hypothesized mechanisms to explain the initiation of endometrial hyperplasia are being pursued. The first hypothesis is that loss of APC impairs the homeostasis between growth and differentiation of myeloid lineage stem/progenitor cells that transdifferentiate into uterine epithelia. An alternate hypothesis is that loss of APC expression affects the inflammatory response of resident uterine macrophages that lead to defects in epithelial morphology. In either case, these genetic studies imply that APC gene defects in myeloid lineage cells may be an initiating event in endometrial cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4330. doi:10.1158/1538-7445.AM2011-4330
Abstract 2775: Meat intake, genetic variation in carcinogen metabolic enzymes, and prostate cancer risk in a multiethnic case-control study of non-Hispanic Whites, African Americans and Hispanics
Authors: Amit D. Joshi, Roman Corral, Chelsea Catsburg, Jocelyn Koo, Esther M. John, Sue A. Ingles, Mariana C. Stern
Journal: Cancer Research (2011)

Abstract Background: The role of meat and meat-induced carcinogens in prostate cancer (PCa) is still inconclusive. The process of cooking meat increases the content of chemical carcinogens such as heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs), which are metabolized to active carcinogens, or detoxified by metabolic enzymes in the liver and the prostate. Study objectives: We tested whether diets high in red or white meats are associated with PCa risk, taking into account cooking practices, and whether polymorphisms in carcinogen metabolism genes modify these associations. Methods: We used data and DNA samples from the California Collaborative Prostate Cancer Study, a multiethnic, population-based study of non-Hispanic White, African American and Hispanic men (717 localized PCa cases, 1,140 advanced PCa cases, and 1,096 controls). We considered nutrient density (g/ 1000 kcal / day) adjusted variables that captured intake of red meat, poultry, and processed meat, taking into account cooking methods, levels of doneness, and estimated meat mutagens, obtained using the CHARRED database. We considered the following polymorphisms: CYP1A2 -154 A&amp;gt;C, CYP1B1 L432V, CYP2E1 -1054 C&amp;gt;T, COX2 -765 G&amp;gt;C, EPHX1 Y113H, GSTP1 I105V, UGT1A6 T181A and the NAT2 predicted phenotype. Conditional logistic regression was used to estimate odds ratios for PCa risk adjusting for age, body mass index, total calorie intake, family history of PCa, saturated fat intake, pack-years of cigarette smoking, total fruit consumption and total vegetable consumption. Results: Diets high in baked poultry, were inversely associated (Ptrend = 0.028), whereas diets high in pan-fried red meat (Ptrend = 0.040) and well done red meat (Ptrend = 0.016) were positively associated with advanced PCa risk. Estimated meat mutagens (PhIP, MeIQX) were positively associated with advanced PCa risk only among Hispanic men (Ptrend = 0.022 and 0.04, respectively). The UGT1A6 T181A polymorphism modified the associations of localized PCa risk with consumption of high temperature cooked, well done, or oven broiled poultry and with estimated PhIP, suggesting positive associations between these exposures and localized PCa risk only among carriers of 1 or 2 copies of the Alanine allele. Conclusions: Diets high in red or white meat cooked with high temperature methods may be modifiable risk factors for advanced PCa, and risk factors for localized disease among carriers of selected metabolic enzyme variants. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2775. doi:10.1158/1538-7445.AM2011-2775
Incidence of Pancreatic Cancer
Authors: Julia Zalokar
Journal: JAMA (1981)

<h3>To the Editor.—</h3> The article "A Multifactorial Model for Pancreatic Cancer in Man" by Lin and Kessler (1980; 245:147) and the accompanying editorial by Berlin and Williams (1980; 245:171) raise two questions: First, has the incidence of pancreatic cancer increased severalfold in the United States in the last few decades as they state? According to Pollack and Horm,<sup>1</sup>mortalities (very close to incidence rates for this usually fatal cancer site) have increased about 30% since 1950. Between 1969 and 1976 the ageadjusted death and incidence rates for cancer of the pancreas have not changed substantially in whites of either sex. Death rates did increase slightly for black women but not for black men. This suggests that the environmental component of the multifactorial causation of this disease has been present for some decades, undoubtedly the case for those who had greater exposure to gasoline and to those exposed to solvents
Internal Body Image of the Brain
Authors: R. Wilf, S. Tyano, H. Munitz, H. Wijsenbeek
Journal: Psychotherapy and Psychosomatics (1983)

We show that there is a body image of an internal organ – the brain. Using questionnaires and drawings to compare three groups – healthy subjects, acutely ill and chronic patients (with a brain disease) – we demonstrate that there is constant body image, which is very little influenced by brain disease.
Should We Treat Acute HIV Infection?
Authors: Brigid Kane
Journal: Annals of Internal Medicine (2001)

Current Clinical Issues15 May 2001Should We Treat Acute HIV Infection?Brigid KaneBrigid KaneSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-134-10-200105150-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Whether it is prudent to treat acute or primary HIV infection aggressively with the currently available potent (and toxic) antiretroviral drugs cannot be determined until more evidence documenting the long-term benefits of the strategy “hit hard, hit very early” has accumulated. As clinical researchers have indicated regarding this situation, such evidence will become available only if newly infected persons are identified by their physicians and offered the opportunity to participate in studies investigating the basic science and clinical aspects of acute HIV infection. Currently, aggressive treatment during acute infection, while promising, is still experimental.Interestingly, the numerous scientific unknowns surrounding ... Author, Article, and Disclosure InformationAuthors: Brigid Kane PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 May 2001Volume 134, Issue 10Page: 1011-1013KeywordsAntiretroviral therapyCellsDrugsHIVHIV infectionsHIV preventionImmune responseInfectious diseasesLymph nodesViral replication ePublished: 15 May 2001 Issue Published: 15 May 2001 Copyright & PermissionsCopyright © 2001 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Poisoning—Treatment and Prevention
Authors: Jay M. Arena
Journal: JAMA (1975)

ACUTE poisoning, unfortunately, is often mismanaged. It is impossible at times to determine whether recovery occurred because of or in spite of the treatment used. Although poisoning is a common pediatric problem, many other specialists are involved (obstetrician, neonatologist, internist, family physician, surgeon, etc), and it has an interface with many disciplines (environmentalism, sociology, and others).  The basic treatment for acute poisoning, whether drug or chemical, is mainly symptomatic and supportive. Overtreatment of the poisoned patient with large doses of non-specific and questionably effective antidotes, stimulants, sedatives, and other therapeutic agents often does far more harm and damage than the poison itself. A calm attitude, with the judicious use of drugs, parenteral fluids, and electrolytes for homeostasis, and the maintenance of an adequate airway is far more effective than heroic measures, which usually are unnecessary.  The four cardinal principles of good management are (1) identification of the drug or chemical