tbuckley/cabot-search huggingface dataset:
Abstract 3131: Androgen receptor promotes ligand-independent prostate cancer progression through c-Myc upregulation.
Authors: Lina Gao, Jacob Schwartzman, Angela Gibbs, Richard Kleinschmidt, Beth Wilmot, Daniel Bottomly, Ilsa Coleman, Peter Nelson, Shannon McWeeney, Joshi J. Alumkal
Journal: Cancer Research (2013)

Abstract Prostate cancer is the most common cancer in men in the United States and the second leading cause of cancer death. The androgen receptor (AR) is the central signaling pathway in prostate cancer. Because of this, androgen deprivation therapy (ADT), which involves reducing levels of androgen ligands or interfering with binding of ligands to AR, has been the major therapeutic focus for the past 70 years. However, in many patients there is no benefit from ADT, and all prostate cancers eventually progress. At progression on ADT, the AR is ubiquitously expressed. For this reason, we contend that AR-dependent mechanisms are critical for prostate cancer progression after ADT. Indeed, recent work demonstrates that the AR can function independently of ligands to promote prostate cancer cell survival. However, specific ligand-independent AR target genes that account for this effect were not well-characterized. We show here that c-Myc, which is a key mediator of ligand-independent prostate cancer progression, is a key ligand-independent AR target gene. Using microarray analysis, we found that c-Myc and AR expression levels strongly correlated with each other in tumors from patients with castration-resistant prostate cancer (CRPC) progressing despite ADT. We confirmed that AR directly regulates c-Myc transcription in a ligand-independent manner, that AR and c-Myc suppression reduces ligand-independent prostate cancer cell growth, and that ectopic expression of c-Myc attenuates the anti-tumor activity of AR suppression. Importantly, treatment with the bromodomain inhibitor JQ1 suppressed c-Myc function and suppressed ligand-independent prostate cancer cell survival. Our results define a new link between two critical proteins in prostate cancer - AR and c-Myc - and demonstrate the potential of AR and c-Myc-directed therapies to improve prostate cancer control. Citation Format: Lina Gao, Jacob Schwartzman, Angela Gibbs, Richard Kleinschmidt, Beth Wilmot, Daniel Bottomly, Ilsa Coleman, Peter Nelson, Shannon McWeeney, Joshi J. Alumkal. Androgen receptor promotes ligand-independent prostate cancer progression through c-Myc upregulation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3131. doi:10.1158/1538-7445.AM2013-3131
Why Are Clinical Laboratory Tests Performed? When Are They Valid?
Authors: Arthur F. Krieg
Journal: JAMA (1975)

TODAY, more than 2 billion medical laboratory tests are performed each year in the United States, at an annual cost that exceeds $6 billion . Three times this volume is predicted for 1980. Does this high utilization indicate better patient care at lower cost through modern medical science? And will the projected increase to 6 billion tests per year by 1980, at an annual cost of $20 billion , represent further progress toward better health? The answer is, not necessarily.  Why do physicians request laboratory tests? Some results—of blood gas, glucose, and electrolyte determinations—are needed to monitor and guide treatment of critically ill patients. Other results—as from creatinine and thyroxine tests—help us to detect early renal or thyroid disease. Still other tests appear to be done primarily because they are available. But in all cases, the usefulness of a positive test result will vary with the sensitivity and specificity of the test,
713. NFkB Decoy Oligodeoxynucleotides Inhibit Osteoclast Differentiation and Activation In Vitro and Improve Osteoporosis of Ovariectomized and Vitamin C Difficient Rat Models
Authors: Hideo Shimizu, Hironori Nakagami, Natsuki Yasumasa, Rie Hanayama, Toshio Ogihara, Ryuichi Morishita
Journal: Molecular Therapy (2006)
Osteopontin Is Expressed in Human Aortic Valvular Lesions
Authors: Kevin D. O’Brien, Johanna Kuusisto, Dennis D. Reichenbach, Marina Ferguson, Cecilia Giachelli, Charles E. Alpers, Catherine M. Otto
Journal: Circulation (1995)

Background Nonrheumatic stenosis of trileaflet aortic valves, in which calcification is a prominent feature, has been termed a “degenerative” condition, but it has been demonstrated recently that chronic inflammation is a characteristic feature of the developing lesion of aortic stenosis. This observation raised the possibility that calcification in the aortic valve might be actively regulated. Thus, the present study investigated whether osteopontin, a protein implicated in the regulation of both normal and dystrophic calcification, could be detected in lesions of valvular aortic stenosis. Methods and Results Morphological and immunohistochemical studies were performed on 14 human aortic valves, representing a range of pathology from normal to clinically stenotic. The extent of calcification and macrophage accumulation and their relation to the presence of osteopontin protein were characterized. Highly statistically significant associations were found between the degree of osteopontin expression and the degrees of both calcification and macrophage accumulation in early through late lesions of aortic stenosis. Further, in situ hybridization localized osteopontin mRNA to a subset of lesion macrophages. Conclusions These results suggest that, rather than representing a degenerative and unmodifiable process, calcification in aortic stenosis may be, in part, an actively regulated process with the potential for control either through modification of inflammation or synthesis of proteins such as osteopontin, which may modulate calcification in this tissue.
Abstract 5018: Evidence for a dynamic interaction between bone marrow and the cutaneous epithelium during skin carcinogenesis by exposure to solar ultraviolet radiation.
Authors: Rebecca J. Morris, Nyssa AK Readio, Ashok Singh, Anupama Singh
Journal: Cancer Research (2013)

Abstract Non-melanoma skin cancer induced by solar ultraviolet radiation (UV) is the most common of epithelial cancers and occurs more frequently in the human population than any other type of malignancy. Therefore, determining its etiology is a significant problem. The objective of this investigation was to determine whether there might be an interaction between epidermal keratinocytes and bone marrow during carcinogenesis induced by solar UV. First, we determined that bone marrow cells were recruited to the cutaneous epithelium where a subpopulation assumed epithelial characteristics during chronic exposure of mice to solar UV radiation. Second, we documented the presence of keratins in blood and bone marrow prior to and during exposure of mice to solar UV radiation by quantitative real time polymerase chain reaction, fluorescence activated cell sorting of freshly harvested cells, and by immunofluorescence microscopy of bone marrow smears. We observed low, but reproducible levels of keratins 8, 14 and 15 in both blood and bone marrow of un-irradiated mice, with a relatively higher expression of keratin 8 in blood, and a relatively higher expression of keratins 14 and 15 in bone marrow. Third, during chronic exposure to solar UV, we detected a dose dependent increase in the percentage of cells expressing keratin 14 in bone marrow: increasing from approximately 1% in un-irradiated control bone marrow, to approximately 10% after 10 weeks of irradiation, with greater increases at later time points. Surprisingly, this increase in keratin expression in bone marrow began many weeks prior to development of benign or malignant cutaneous neoplasms. Fourth, because these results could suggest a possible egress of keratinocytes from the cutaneous epithelium and homing to the bone marrow, we performed in vitro keratinocyte migration assays with bone marrow as bait. We observed a significant and reproducible migration of epidermal keratinocytes towards bone marrow over controls such as 3T3 cells, fetal bovine serum, or other keratinocyte cultures. We conclude from these studies that there is a dynamic interaction between the cells of the cutaneous epithelium and the bone marrow. The cells and the mechanisms involved in this interaction are currently under investigation. Citation Format: Rebecca J. Morris, Nyssa AK Readio, Ashok Singh, Anupama Singh. Evidence for a dynamic interaction between bone marrow and the cutaneous epithelium during skin carcinogenesis by exposure to solar ultraviolet radiation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5018. doi:10.1158/1538-7445.AM2013-5018
More ways than one to slip on a banana: unusual forms of water sport injuries.
Authors: C Clinton
Journal: British Journal of Sports Medicine (1992)

This paper reviews ten cases that presented to this Department, during a 2-week period in August 1991.The injuries were all caused by falling/slipping off a 'Banana', representing unusual forms of water sport injuries.A 'Banana' is the nickname given to an inflatable craft which is towed behind a speedboat.Its full name is a 'Bronco Fun-Rider' and it is a long, yellow, banana-shaped inflatable craft with straps for holding on to along its length.The idea is for people to sit behind one another astride the 'Banana' and remain seated during the ride while the speedboat tows the 'Banana' out to sea at a speed usually of 20-25 mph (the riders wear life-jackets).The injuries were all different in nature.Age range was 10-47 (mean 25) years; sex ratio male:female was 4:6; three were local residents and seven holiday makers.
Death by footwear
Authors: P. Perkins
Journal: Journal of the Royal Society of Medicine (2004)

Dr Greenberg (July 2004 JRSM1) seeks an explanation for a cluster of deaths registered between 1894 and 1900 due to footwear. One possible theory is the rupture of a saccular popliteal aneurysm due to pressure trauma from tight knee-length boots worn by the cavalry and fashionable society. An example of the former may be found in a post mortem pot in the Gordon Museum at Guy's.

Thomson and Miles' Manual of Surgery published in 1909 mentions a further cause of popliteal aneurysms previously very common in post boys—the repeated flexion and extension of the knee in riding.2

Time will tell if current shoe trends will harm anything other than the wallet.
THE USE OF CORTIN IN A CASE OF ACUTE HYPOSUPRARENALISM OCCURRING AS A SEQUELA OF ACUTE STREPTOCOCCIC SORE THROAT
Authors: J. Holden Robbins
Journal: JAMA (1933)

<h3>History.</h3> —A woman, aged 25, on the afternoon of April 7, began to have symptoms of general malaise, aching pains throughout the body, headache and slightly sore throat. There was no cough or expectoration, nor were there symptoms referable to the central nervous, cardiovascular, gastro-intestinal or genito-urinary systems. The patient had made a complete recovery three days previously from an attack of acute appendicitis, without operation. <h3>Examination.</h3> —Physical examination revealed the following pertinent points: The patient was well developed and well nourished. The temperature was 99.6 F., pulse 90, respiration rate 20. The mucous membrane of the nasal cavity was inflamed and congested, the tongue coated, the pharynx inflamed. The tonsils were inflamed and enlarged. There was no rigidity and no abnormal pulsations in the neck; there were a few enlarged cervical lymph nodes. The chest was well developed; the expansion was good and equal; the resonance was normal throughout;
THE HUMAN SPLEEN AS AN HÆMATOPLASTIC ORGAN, AS EXEMPLIFIED IN A CASE OF SPLENOMEGALY WITH SCLEROSIS OF THE BONE-MARROW
Authors: J. L. Donhauser
Journal: The Journal of Experimental Medicine (1908)

1. The nodules found in the spleen are islands of active haematoplastic tissue. 2. The bone-marrow, at least in the case which has been described, has been the primary focus of disease; some toxin has probably produced a chronic inflammatory change. 3. The bone-marrow, owing to its enormous sclerosis, has lost its haemopoëtic powers totally or to a marked degree and the spleen has reverted to its foetal power to form blood.
On the Use of Antiseptic Cere-Cloth for Covering Wounds
Authors: E. Lund
Journal: BMJ (1869)

but we do know, in some respects, what the people were in Queen Elizabeth's reign.They were not a perfect race, but they had many great qualities.At that date seven millions, at the last census nearly thirty millions, of the race existed in these islands; besides the swarming millions in the New World and in Australasia.Is there any correlative improvement in the fine qualities of this race?There is, in many qualities.Yet it is impossible to pass the population in review at a census without observing in many grave defects; in many, shortcomings; in many, organic degeneracies; in many, criminal de- pravities.In large portions of the world, only low and barbarous races roam.How, out of the existing seed, to raise races of men to a divine perfection, is the final problem of Public Medicine.
Gastric involvement in AIDS associated cryptosporidiosis
Authors: P Rossi, F Rivasi, M Codeluppi, A Catania, A Tamburrini, E Righi, E Pozio
Journal: Gut (1998)

Background —Cryptosporidiosis has been shown to be a common cause of diarrhoea in both immunocompetent and immunosuppressed individuals. There are very few data on the distribution of Cryptosporidium parvum along the gastrointestinal tract. Aims —To evaluate the location of Cryptosporidium parasites in the digestive tract of patients with AIDS. Methods —Gastrointestinal localisation of C parvum was studied in 71 patients with AIDS who underwent upper and/or lower endoscopy with biopsy for chronic diarrhoeal illness and/or other gastrointestinal disorders of unexplained origin. Results —Twenty four individuals (33.8%) were positive for C parvum , of which 16 (88.9%) had parasites in the gastric epithelium. Most patients with gastric localisation of C parvum did not show specific symptoms indicating the presence of this parasite in the stomach. Conclusions —Gastric involvement in AIDS related cryptosporidiosis is more frequent than expected, but no clear correlation between gastric location and related clinical and pathological features was observed.
Contraceptive practice and unplanned pregnancy among single university students.
Authors: J B Cole, F C Beighton, I H Jones
Journal: BMJ (1975)

The sexual behaviour and contraceptive practices of a random sample of unmarried university students were compared with those of a group attending the student health service with an unplanned pregnancy. The immediate cause of most pregnancies in this series was incorrect use of a rhythm method. Irregularity of the menstrual cycle may have been a contributing factor in many cases. Psychological factors influencing the desire for pregnancy, while present, were not major contributing causes in many pregnancies.
EXERCISE TRAINING IMPROVES LV MASS, LV END DIASTOLIC VOLUME AND STROKE VOLUME AND REDUCES UPRIGHT HEART RATE IN THE POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME
Authors: Paul S. Bhella, Tiffany B. VanGundy, Qi Fu, Benjamin D. Levine
Journal: Journal of the American College of Cardiology (2010)
US workers bear cost increase in employer based health insurance
Authors: B. Roehr
Journal: BMJ (2010)

The overall cost of employer based health insurance in the United States rose by only 3% from 2009 to 2010, but almost all the increase was paid for by workers out of their own pockets rather than the companies they work for, new figures show.

The 12th annual report on employer health benefits from the Kaiser Family Foundation and the Health Research and Educational Trust, both non-profit organisations working in health policy, shows that the average annual total premium for family health insurance coverage rose to $13 770 (£8940; €10 730) in 2010.

Though this was only a 3% overall rise on the 2009 …
Microvascular Injury: Vasculitis, Stasis and Ischaemia
Authors: E. DORINDA LOEFFEL
Journal: JAMA (1978)

Until recently, the physician faced with the ominous diagnosis of vasculitis could do little more than speculate about possible causes and cures. Indeed, even attempting to classify the type of vasculitis was difficult, as 19th and 20th century lumpers and splitters had created a chaos of descriptive terms meaning different things to different people, such as "periarteritis nodosa" and "polyarteritis nodosa." Fortunately, help is now available in this excellent, comprehensive, well-organized British text. The book uses "microvascular injury" synonomously with vasculitis and concentrates on injury to the small blood vessels of the skin. Such injury is triggered by many factors, including bacterial toxins, drugs, immune complexes, and food additives, which lead to a wide spectrum of clinical and pathological findings. Mild vasculitis, caused by transient vessel injury, presents with combinations of purpura, urticaria, and erythema, while more prolonged vessel injury causes bullae, necrosis, and ulceration. The detailed pathophysiological mechanisms of
The phytochrome gene family in grasses (Poaceae): a phylogeny and evidence that grasses have a subset of the loci found in dicot angiosperms
Authors: S. Mathews, R. A. Sharrock
Journal: Molecular Biology and Evolution (1996)

The phytochrome nuclear gene family encodes photoreceptor proteins that mediate developmental responses to red and far red light throughout the life of the plant. From studies of the dicot flowering plant Arabidopsis, the family has been modeled as comprising five loci, PHYA-PHYE. However, it has been shown recently that the Arabidopsis model may not completely represent some flowering plant groups because additional PHY loci related to PHYA and PHYB of Arabidopsis apparently have evolved independently several times in dicots, and monocot flowering plants may lack orthologs of PHYD and PHYE of Arabidopsis. Nonetheless, the phytochrome nucleotide data were informative in a study of organismal evolution because the loci occur as single copy sequences and appear to be evolving independently. We have continued our investigation of the phytochrome gene family in flowering plants by sampling extensively in the grass family. The phytochrome nuclear DNA data were cladistically analyzed to address the following questions: (1) Are the data consistent with a pattern of differential distribution of phytochrome genes among monocots and higher dicots, with homologs of PHYA, B, C, D, and E present in higher dicots, but of just PHYA, B, and C in monocots, and (2) what phylogenetic pattern within Poaceae do they reveal? Results of these analyses, and of Southern blot experiments, are consistent with the observation that the phytochrome gene family in grasses comprises the same subset of loci detected in other monocots. Furthermore, for studies of organismal phylogeny in the grass family, the data are shown to provide significant support for relationships that are just weakly resolved by other data sets.
Prevalence of symptoms of dyspepsia in the community.
Authors: R. Jones, S. Lydeard
Journal: BMJ (1989)

To study the prevalence of dyspepsia in the community a postal questionnaire was sent to 2697 patients who were selected at random from the lists of patients registered in two health centres in Hampshire. A total of 2066 returned questionnaires were suitable for analysis (response rate 77%). It was found that the six month prevalence of dyspepsia was 38%. There was considerable overlap between symptoms of heartburn and upper abdominal pain, with over half of patients with dyspepsia experiencing both. One in four of these patients had consulted their general practitioner during that time. The proportion of patients with dyspepsia who consulted their general practitioner varied widely among the eight doctors who participated in the study, from 17% to 45%. Frequency of symptoms tended to fall with age, particularly in men, while the proportion of patients with dyspepsia who sought medical advice increased with age. Almost one in five of the 2066 patients had been investigated with radiology or endoscopy at some time, and 143 (7%) of them claimed to have had a diagnosis of peptic ulcer.
More on autonomic neuropathy in systemic sclerosis.
Authors: P H Dessein, R F Gledhill
Journal: Annals of the Rheumatic Diseases (1988)

Phenytoin in rheumatoid arthritis SIR, We were interested to read the comparative study of phenytoin and gold in rheumatoid arthritis (RA) by Richards et al,' prompted by the work of Macfarlane et al, who had shown improvements in clinical and laboratory tests and suggested that phenytoin may, therefore, have properties of a second line drug.2Richards et al found phenytoin to have significant beneficial effects on haemo- globin and the erythrocyte sedimentation rate but on only one of four clinical measurements.We have also studied phenytoin in RA,3 but without knowledge of other work in progress.Our interest was stimulated by several properties of phenytoin, including inhibition of collagenase and stimulation of collagen synthesis4 5; there appeared to be possible implications with respect to prevention and reversal of rheumatoid bone loss.In an open study with follow up after drug withdrawal we found significant improvements in clinical measurements over 32 weeks; serum C reactive protein, plasma viscosity, and haemoglobin also improved, but changes were not significant.Three independent studies have, therefore, shown slightly divergent although positive results with phenytoin in RA.Richards et al commented that phenytoin may be unique among second line drugs in having a greater effect on laboratory than on clinical tests, though Macfarlane et al and we showed significant clinical improvement, albeit in open studies.Confirmation of a positive effect of phenytoin on the erythrocyte sedimentation rate is, how- ever, of particular interest because its control within the normal range may reduce the rate of bone erosion.6 7The most appropriate assessment of phenytoin in RA may be by its long term effects on bone assessed radiographically and to our knowledge this has not been examined.Although 'phenytoin is unlikely to become a first choice second line agent',' it should not now be dismissed.
Heberden Oration, 1977. Chronic arthritis in childhood.
Authors: B M Ansell
Journal: Annals of the Rheumatic Diseases (1978)

This I do with considerable trepidation, remembering the superb Orations I have heard and looking at the list of my distinguished predecessors which includes Eric Bywaters, who in 1966 surveyed Still's disease.In his summary he said, 'chronic juvenile polyarthritis is a wide term, Still's disease is an historical term, juvenile rheumatoid arthritis an exact but misleading term'.He considered that criteria chosen and verified by international agree- ment were necessary for further elucidation of chronic arthritis in childhood (Bywaters, 1967).Eleven years have now passed.The growing interest in paediatric rheumatology has been reflected in the number of sessions devoted to it in meetings, the many papers published from Scan- dinavia, Europe, not forgetting Taplow and the Americas, particularly the United States.The suggested criteria have been constantly modified (Brewer et al., 1977) and have not yet received general acceptance.At the workshop organised by