tbuckley/cabot-search huggingface dataset:
Ovarian Transplantation between Monozygotic Twins Discordant for Premature Ovarian Failure
Authors: Sherman J. Silber, Kathleen M. Lenahan, David J. Levine, Jorge A. Pineda, Kim S. Gorman, Michael J. Friez, Eric C. Crawford, Roger G. Gosden
Journal: New England Journal of Medicine (2005)

Monozygotic 24-year-old twins presented with discordant ovarian function. One had had premature ovarian failure at the age of 14 years, whereas her sister had normal ovaries and three naturally conceived children. After unsuccessful egg-donation therapy, the sterile twin received a transplant of ovarian cortical tissue from her sister by means of a minilaparotomy. Within three months after transplantation, the recipient's cycles resumed and serum gonadotropin levels fell to the normal range. During the second cycle, she conceived, and her pregnancy progressed uneventfully. At 38 weeks' gestation, she delivered a healthy-appearing female infant.
Safety and Antiviral Activity of Albinterferon Alfa-2b in Prior Interferon Nonresponders With Chronic Hepatitis C
Authors: David R. Nelson, Vinod Rustgi, Vijayan Balan, Mark S. Sulkowski, Gary L. Davis, Andrew J. Muir, Louis R. Lambiase, Rolland C. Dickson, Russell H. Weisner, Michele Fiscella, Patrick W. Cronin, Erik Pulkstenis, John G. McHutchison, G. Mani Subramanian
Journal: Clinical Gastroenterology and Hepatology (2008)
Benzene Exposure and Aplastic Anemia Followed by Leukemia 15 Years Later
Authors: Richard L. DeGowin
Journal: JAMA (1963)

A painter who was exposed to benzene for 13 years developed a hypocellular bone marrow and pancytopenia. During the 15 years after recovery from aplastic anemia, there were found in the peripheral blood leukopenia, thrombocytopenia, and anemia. Night sweats, petechiae, splenomegaly, and pancytopenia prompted examination of the marrow, which was found to be characteristic of acute myelogenous leukemia.
GENDER DIFFERENCES IN ALL-CAUSE DEATH BY EXTENT AND SEVERITY OF CORONARY ARTERY DISEASE BY CARDIAC COMPUTED TOMOGRAPHIC ANGIOGRAPHY: A MATCHED ANALYSIS OF THE CONFIRM REGISTRY
Authors: Fay Lin, Kavitha Chinnaiyan, Allison M. Dunning, Leslee J. Shaw, Stephan Achenbach, Mouaz Al-Mallah, Daniel S. Berman, Matthew J. Budoff, Filippo Cademartiri, Tracy Q. Callister, Hyuk-Jae Chang, Benjamin J.W. Chow, Augustin J. Delago, Joerg Hausleiter, Martin Hadamitzky, Philipp Kaufmann, Gilbert L. Raff, Todd Villines, James K. Min
Journal: Journal of the American College of Cardiology (2011)
Effect of the combination of diltiazem and atenolol on exercise-induced regional myocardial ischemia in conscious dogs.
Authors: M Matsuzaki, B Guth, T Tajimi, W S Kemper, J Ross
Journal: Circulation (1985)

The effect of combination therapy with diltiazem and atenolol on the regional myocardial blood flow-function relationship was studied in eight conscious dogs with chronic coronary artery stenosis. An ameroid constrictor and hydraulic occluder were placed around the left circumflex coronary artery, sonomicrometers were implanted for measuring wall thickness in control and ischemic regions, and regional myocardial blood flow was measured with the microsphere method. Eighteen days (average) after surgery, resting regional myocardial function and blood flow were normal, but treadmill exercise induced severe regional myocardial dysfunction in the posterior wall (wall thickening during systole reduced from 25.5% to 2.7%, a 90% reduction). Subendocardial blood flow decreased by 68% from the control standing value, while subepicardial flow increased. An identical exercise bout was performed 3 hr after administration of atenolol (1.0 mg/kg orally) and 15 min after administration of diltiazem (0.3 mg/kg iv). Heart rate during running was significantly lower as were left ventricular peak systolic pressure, end-diastolic pressure, and peak dP/dt. Wall thickening in the control region was not augmented during exercise after atenolol and diltiazem. There was less dysfunction in the ischemic region (35% reduction) and the improved performance was accompanied by a substantial increase in subendocardial perfusion (0.31 +/- 0.14 vs 0.61 +/- 0.30 ml/min/g, a 36% reduction from rest). Epicardial flow was unchanged, and the endocardial/epicardial ratio increased (0.27 +/- 0.13 vs 0.62 +/- 0.29). Recovery time for regional wall thickening also improved. The beneficial effects of the combination of atenolol and diltiazem in a preparation of single-vessel chronic coronary stenosis were shown to be significantly greater than those of either drug alone.
Characterization of a Mouse Model of Allergy to a Major Occupational Latex Glove Allergen Hev b 5
Authors: Charles L. Hardy, Linda Kenins, Alexander C. Drew, Jennifer M. Rolland, Robyn E. O'Hehir
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Allergen-specific immunotherapy is a clinically proven effective treatment for many allergic diseases, including asthma; however, it is not currently available for latex allergy because of the high risk of anaphylaxis. There is, therefore, a crucial need for an animal model of latex allergy in which to develop effective immunotherapy. Previous mouse models of latex allergy either did not characterize the allergic pulmonary immune response or used crude latex extracts, making it difficult to quantify the contribution of individual proteins and limiting their usefulness for developing specific immunotherapy. We immunized mice with recombinant Hev b 5, a defined major latex allergen, or latex glove protein extract, representing the range of occupationally encountered processed latex allergens. The immune response was compared with that seen in ovalbumin-immunized mice. Immunization with Hev b 5 or glove extract elicits hallmarks of allergic pulmonary Th2-type immune responses, comparable to those for ovalbumin, including (1) serum antigen-specific IgE, (2) an eosinophilic inflammatory infiltrate in the lung, (3) increased interleukin-5 in lung bronchoalveolar lavage fluid, and (4) mucus hypersecretion by epithelial cells in the lung airways. This mouse model will aid the development of potentially curative treatments for latex-sensitized individuals, including those with occupational asthma.
Predictors of postmenopausal osteoporosis: Authors' reply
Authors: J. Hodson
Journal: BMJ (2003)

EDITOR—Our study was designed, performed, and analysed from a primary care viewpoint. The national service framework recommends that general practitioners refer high risk patients with any of the accepted risk factor criteria for dual x ray absorptiometry.1 2 The low specificity of this selection method results in many women without osteoporosis being referred.



Receiver operating characteristic curves for risk factors alone and ultrasound T score as continuous variable



There is currently no guidance for general practitioners to use risk factor information in the way Wong et …
Effects of Abiraterone Acetate on Androgen Signaling in Castrate-Resistant Prostate Cancer in Bone
Authors: Eleni Efstathiou, Mark Titus, Dimitra Tsavachidou, Vassiliki Tzelepi, Sijin Wen, Anh Hoang, Arturo Molina, Nicole Chieffo, Lisa A. Smith, Maria Karlou, Patricia Troncoso, Christopher J. Logothetis
Journal: Journal of Clinical Oncology (2011)

Purpose Persistent androgen signaling is implicated in castrate-resistant prostate cancer (CRPC) progression. This study aimed to evaluate androgen signaling in bone marrow–infiltrating cancer and testosterone in blood and bone marrow and to correlate with clinical observations. Patients and Methods This was an open-label, observational study of 57 patients with bone-metastatic CRPC who underwent transiliac bone marrow biopsy between October 2007 and March 2010. Patients received oral abiraterone acetate (1 g) once daily and prednisone (5 mg) twice daily. Androgen receptor (AR) and CYP17 expression were assessed by immunohistochemistry, testosterone concentration by mass spectrometry, AR copy number by polymerase chain reaction, and TMPRSS2-ERG status by fluorescent in situ hybridization in available tissues. Results Median overall survival was 555 days (95% CI, 440 to 965+ days). Maximal prostate-specific antigen decline ≥ 50% occurred in 28 (50%) of 56 patients. Homogeneous, intense nuclear expression of AR, combined with ≥ 10% CYP17 tumor expression, was correlated with longer time to treatment discontinuation (&gt; 4 months) in 25 patients with tumor-infiltrated bone marrow samples. Pretreatment CYP17 tumor expression ≥ 10% was correlated with increased bone marrow aspirate testosterone. Blood and bone marrow aspirate testosterone concentrations declined to less than picograms-per-milliliter levels and remained suppressed at progression. Conclusion The observed pretreatment androgen-signaling signature is consistent with persistent androgen signaling in CRPC bone metastases. This is the first evidence that abiraterone acetate achieves sustained suppression of testosterone in both blood and bone marrow aspirate to less than picograms-per-milliliter levels. Potential admixture of blood with bone marrow aspirate limits our ability to determine the origin of measured testosterone.
The Chicken or the Egg—Idiopathic Hypercalciuria
Authors: RALPH S. GOLDSMITH
Journal: Annals of Internal Medicine (1973)

Editorial Notes1 June 1973The Chicken or the Egg—Idiopathic HypercalciuriaRALPH S. GOLDSMITH, M.D., LYNWOOD H. SMITH, M.D.RALPH S. GOLDSMITH, M.D.Search for more papers by this author, LYNWOOD H. SMITH, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-6-967 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptEver since the syndrome known as idiopathic hypercalciuria was identified by Flocks (1) and Henneman and associates (2), concern over the possibility that the syndrome was caused by underlying hyperparathyroidism has been a recurring theme. Several of the patients initially studied by Henneman's group were, in fact, found, on parathyroid exploration, to have histologically normal glands. Subsequently, Yendt and Gagne (3) recognized that some normocalcemic women with this syndrome had primary hyperparathyroidism and could be cured by parathyroidectomy; they indicated, however, that such may not be the case in men. Shieber and his collaborators (4) reopened the question by reporting...References1. FLOCKS R: Prophylaxis and medical management of calcium urolithiasis: the role of the quantity and precipitability of the urinary calcium. Trans Southeast Branch Am Urol Assoc 1939, pp. 59-66 Google Scholar2. HENNEMANBENEDICTFORBES PPA: Idiopathic hypercalcuria. N Engl J Med 259:802-807, 1958 CrossrefMedlineGoogle Scholar3. YENDTGAGNE ER: Detection of primary hyperparathyroidism, with special reference to its occurrence in hypercalciuric females with "normal" or borderline serum calcium. Can Med Assoc J 98:331-336, 1968 MedlineGoogle Scholar4. SHIEBERBIRGEAVIOLI WSL: Normocalcemic hyperparathyroidism with "normal" parathyroid glands. Arch Surg 103:299-302, 1971 CrossrefMedlineGoogle Scholar5. COECANTERBURYFIRPO FJJ: Evidence for secondary hyperparathyroidism in idiopathic hypercalciuria. J Clin Invest 52:134-142, 1973 CrossrefMedlineGoogle Scholar6. SMITHTHOMASARNAUD LWC: Orthophosphate therapy in calcium renal lithiasis, in Proceedings of the Symposium on Renal Stone Research, Madrid, Spain. In press, 1973 Google Scholar7. CANTERBURYLEVEYREISS JGE: Activation of renal cortical adenylate cyclase by circulating immunoreactive parathyroid hormone fragments. J Clin Invest 52:524-527, 1973 CrossrefMedlineGoogle Scholar8. STOTESMITHWILSON RLD: Hydrochlorothiazide effects on serum calcium and immunoreactive parathyroid hormone concentrations. Studies in normal subjects. Ann Intern Med 77:587-591, 1972 LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Mineral Research Group Mayo Clinic and Mayo Foundation Rochester, Minnesota PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1973Volume 78, Issue 6Page: 967-967KeywordsHyperparathyroidismParathyroidParathyroidectomy Issue Published: 1 June 1973 PDF downloadLoading ...
David R Bowsher
Authors: J. Miles
Journal: BMJ (2012)

David R Bowsher was born in Wiltshire, in England, but he always insisted that he was Welsh, as was his mother. He had close relatives in Wales and latterly was learning the language.

He undertook medicine at the insistence of his father, a chemical pathologist, although his interest was always in the basic sciences around medicine.

After junior appointments in Manchester and Liverpool he joined the department of anatomy at the University of Liverpool, though his subsequent career was in experimental physiology, and he later became a clinical honorary neurologist and pain …
Transcriptional rate and steady-state changes of retinoblastoma mRNA in regenerating rat liver
Authors: Betsy T. Kren, Amy L. Teel, Clifford J. Steer
Journal: Hepatology (1994)

This study characterizes the mRNA expression of the retinoblastoma tumor suppressor gene in regenerating rat liver during 96 hr after 70% partial hepatectomy. A 960-bp BglII-OxaNI fragment of murine retinoblastoma cDNA was used to probe Northern blots of poly(A)(+)-enriched RNA isolated from regenerating liver. Two species of retinoblastoma mRNA, 2.8 kb and 4.7 kb long, were identified in control liver and exhibited an intensity ratio of 5:1, respectively. Expression of the 2.8-kb mRNA was reduced by 50% 1 hr after partial hepatectomy and was less than 10% of control values by 3 hr. The transcript began to reappear at 12 hr and returned to near-baseline levels by 24 hr. In contrast to the rapid disappearance of the 2.8-kb transcript, expression of the 4.7-kb mRNA increased 15-fold by 6 hr and returned to control levels by 18 hr after partial hepatectomy. Pretreatment of the animals with cycloheximide before partial hepatectomy completely stabilized steady-state levels of both mRNA transcripts through 6 hr. Nuclear run-on assays revealed a sixfold increase in transcription by 30 min and a return to near-baseline levels by 6 hr. The in vivo half-lives of the 2.8- and 4.7-kb transcripts in control livers were 39.5 and 41.2 min, respectively. The half-life of the 4.7-kb transcript 6 hr after partial hepatectomy was 39.1 min. Intravenous administration of transforming growth factor-beta 1, a known inhibitor of hepatocyte replication, just before partial hepatectomy caused no significant change in the modulation of the transcripts through 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)
Critical Role of Smad2 in Tumor Suppression and Transforming Growth Factor-β–Induced Apoptosis of Prostate Epithelial Cells
Authors: Jiayi Yang, Reema Wahdan-Alaswad, David Danielpour
Journal: Cancer Research (2009)

Transforming growth factor-beta (TGF-beta) functions as a tumor suppressor of the prostate through mechanisms that remain unresolved. Although TGF-beta receptors directly activate both Smads 2 and 3, to date, Smad3 has been shown to be the essential mediator of most Smad-dependent TGF-beta responses, including control of gene expression, cell growth, apoptosis, and tumor suppression. Using a robust lentiviral short hairpin RNA system to silence Smads 2 and/or 3 in the NRP-152 nontumorigenic rat prostate basal epithelial cell line, we provide the first evidence for Smad2 as a critical mediator of TGF-beta-induced apoptosis and gene expression. Parallel analyses revealed that Smad3 is the major mediator of TGF-beta-induced transcriptional and apoptotic responses in the NRP-154 rat prostate carcinoma cell line. Remarkably, silencing Smad2 alone caused malignant transformation of NRP-152 cells, as assayed by s.c. tumor growth in athymic mice, whereas silencing Smad3 alone did not induce tumors. Nevertheless, tumors induced by silencing both Smads 2 and 3 were larger than those from silencing Smad2 alone. Given previous reports that NRP-152 cells have a stem cell phenotype, we speculate a critical role for Smad2 as a tumor suppressor in the basal epithelial or stem cell compartment of the prostate.
Hepatic stellate cells are not subjected to oxidant stress during iron-induced fibrogenesis in rodents
Authors: Giuliana Montosi, Cinzia Garuti, Sabrina Martinelli, Antonello Pietrangelo
Journal: Hepatology (1998)

Oxidant stress plays a key role in hepatic fibrogenesis. This study was undertaken to assess whether, during iron overload-associated liver fibrosis ain vivo , oxidant stress occurs in hepatic stellate cells (HSC) during active fibrogenesis. Gerbils were treated with iron-dextran, and, after hepatic fibrosis developed, livers were subjected to various combination of in situ hybridization and immunocytochemistry analyses. In iron-treated animals, no specific accumulation of ferritin protein was found in collagen mRNA-expressing cells. Moreover, the activity of the iron regulatory protein, the main sensor of cellular iron status, was unchanged in HSC from iron-treated animals. Although a significant amount of malondialdehyde-protein adducts was detected in gerbil liver during fibrogenesis, accumulation of these lipid peroxidation by-products was restricted to iron-laden cells adjacent to activated HSC. In cultured gerbil HSC, iron, aldehydes, and other pro-oxidants were able to enhance the expression of an oxidant stress-responsive gene, heme oxygenase (HO), with no change in collagen mRNA accumulation. In keeping with these findings, we found that, in vivo , activation of HO gene was present in iron-filled nonparenchymal cell aggregates, but absent in HSC. In conclusion, the data indicate that during iron overload-associated fibrogenesis, HSC are not directly subjected to oxidant stress, but are likely to be activated by paracrine signals arising in neighboring cells.
Dietary Lipid Lowering Reduces Tissue Factor Expression in Rabbit Atheroma
Authors: Masanori Aikawa, Sami J. Voglic, Seigo Sugiyama, Elena Rabkin, Mark B. Taubman, John T. Fallon, Peter Libby
Journal: Circulation (1999)

The mechanisms by which lipid lowering reduces the incidence of acute thrombotic complications of coronary atheroma in clinical trials remains unknown. Tissue factor (TF) overexpressed in atheroma may accelerate thrombus formation at the sites of plaque disruption. A cell surface cytokine CD40 ligand (CD40L) enhances TF expression in vitro.To test the hypothesis that lipid lowering reduces TF expression and activity, we produced atheroma in rabbit aortas by balloon injury and cholesterol feeding for 4 months (Baseline group, n=15), followed by either a chow diet (Low group, n=10) or a continued high-cholesterol diet for 16 months (High group, n=5). Immunolocalization of TF, CD40L, and its receptor CD40 was quantified by computer-assisted color image analysis. Macrophages in atheroma of the Baseline and High groups strongly expressed TF. Intimal smooth muscle cells and endothelial cells also contained immunoreactive TF. Regions of expression of CD40L and CD40 colocalized with TF. Protein expression of TF diminished substantially in the Low group in association with reduced expression of CD40L and CD40. In situ binding of TF to factors VIIa and X, detected by digoxigenin-labeled factors VIIa and X, colocalized with TF protein in atheroma and decreased after lipid lowering. We also determined reduced TF biological activity in the Low group by use of a chromogenic assay. The level of TF mRNA detected by reverse transcription-polymerase chain reaction also decreased after lipid lowering.These results suggest decreased expression and activity of TF as a novel mechanism of reduced incidence of thrombotic complications of atherosclerosis by lipid lowering.
INTRAVENOUS CLODRONATE IN THE TREATMENT AND RETREATMENT OF PAGET'S DISEASE OF BONE
Authors: A.J.P. Yates, R.E.S. Gray, G.H. Urwin, C.J. Preston, R.G.G. Russell, R.C. Percival, R.M. Atkins, N.A.T. Hamdy, M.N.C. Beneton, J.A. Kanis
Journal: The Lancet (1985)
Global Noncommunicable Diseases — Lessons from the HIV–AIDS Experience
Authors: K.M. Venkat Narayan, Mohammed K. Ali, Carlos del Rio, Jeffrey P. Koplan, James Curran
Journal: New England Journal of Medicine (2011)

In preparation for the UN General Assembly's upcoming meeting on addressing global noncommunicable diseases, it is worth reexamining the global experience with HIV–AIDS for lessons that may be applicable to initiatives for noncommunicable diseases.
THE INFLUENCE OF THYROID PRODUCTS ON THE PRODUCTION OF MYOCARDIAL NECROSIS
Authors: Ernest W. Goodpasture
Journal: The Journal of Experimental Medicine (1921)

An experimental study upon the demonstrable effects of large doses of dried thyroid gland and thyroxin upon the myocardium of rabbits has been made. Animals under such treatment show characteristic clinical symptoms with definite, although relatively slight, myocardial lesions. Similarly treated animals which have, in addition, been subjected to chloroform anesthesia show more striking, widespread myocardial necrosis. These experiments indicate very distinctly that chloroform as an anesthetic in cases of hyperthyroidism is apt to be exceptionally detrimental to the myocardium, and should be avoided.
Functional alterations of cardiac proteasomes under physiological and pathological conditions
Authors: O. Tsukamoto, T. Minamino, M. Kitakaze
Journal: Cardiovascular Research (2009)

The cardiac proteasome is a complex, heterogeneous, and dynamic organelle. Its function is regulated by its molecular organization, post-translational modifications, and associated partner proteins. Pressure overload, ischaemic heart disease, or genetic mutations in contractile proteins can cause heart failure, during which misfolded protein levels are elevated. At the same time, numerous interconnected signal transduction pathways are activated that may modulate any of the three proteasomal regulatory mechanisms mentioned above, resulting in functional changes in cardiac proteasomes. Many lines of evidence support the important role of the ubiquitin-proteasome system (UPS) in the development of heart diseases. Many researchers have focused on the UPS, applying new drug discovery methods not only in the field of cancer research but also in cardiovascular fields such as cardiac hypertrophy and ischaemic heart diseases. More understanding of UPS in the pathophysiology of heart diseases will lead to new routes for therapy.
End-Tidal Pco2 During Cardiopulmonary Resuscitation
Authors: Max Harry Weil
Journal: JAMA (1990)

To the Editor.—  The contribution by Sanders et al 1 strongly supports a series of earlier studies by our group, both experimental and clinical, on the rationale and hemodynamic significance of the end-tidal carbon dioxide tension (P ET CO 2 ) during cardiac arrest. 2-4 Sanders and colleagues also deserve recognition for having initially observed a close relationship between P ET CO 2 and coronary perfusion pressure, an observation that we subsequently confirmed. 5,6   The importance of the P ET CO 2 measurement may, however, have been understated by the authors if it is viewed primarily as a prognostic indicator. In our own experience, it is the continuous measurement of P ET CO 2 and the extent to which the P ET CO 2 is moderated by therapeutic interventions that provides unique opportunities for therapeutic decision making. Yes, in the final analysis, the failure to achieve viable P ET CO 2
PROGNOSTIC IMPLICATIONS OF ATHEROGENIC/ANTI-ATHEROGENIC LIPID RATIOS IN AN ETHNICALLY DIVERSE POPULATION.
Authors: Palaniappan Manickam, Ankit Rathod, Apurva Badheka, Vikas Veeranna, Pawan Hari, Ashutosh Niraj, Sony Jacob, Luis Afonso
Journal: Journal of the American College of Cardiology (2010)