tbuckley/cabot-search huggingface dataset:
Childhood CML in blastic stage: An analysis of cell markers and cell kinetics
Authors: J. D. Beck, M. Andreeff, R. Mertelsmann, M. Haghbin, C. Tan, D. R. Miller, R. A. Good, S. Gupta
Journal: American Journal of Hematology (1980)

Abstract The clinical course of Ph+ CML and their terminal blastic stage is described in the following case histories. During blastic phase, cell surface markers, terminal deoxynucleotidyl transferase (TdT) activity, and flow cytometric measurements were used for determination of the blast cell phenotype which was undifferentiated by morphological and cytochemical criteria. A high proportion of blast cells expressed Fc receptors for IgG, TdT activity was normal in both children, and RNA measurements of single cells by flow cytometry showed a high RNA content in the majority of blasts. These findings are compatible with the phenotype seen in myelomonocytic leukemias. Flow cytometry appears to be a useful adjunct to immunological methods and TdT activity for the rapid characterization of CML in blastic phase.
Intrarectal pressures and balloon expulsion related to evacuation proctography.
Authors: S Halligan, J Thomas, C Bartram
Journal: Gut (1995)

Seventy four patients with constipation were examined by standard evacuation proctography and then attempted to expel a small, non-deformable rectal balloon, connected to a pressure transducer to measure intrarectal pressure. Simultaneous imaging related the intrarectal position of the balloon to rectal deformity. Inability to expel the balloon was associated proctographically with prolonged evacuation, incomplete evacuation, reduced anal canal diameter, and acute anorectal angulation during evacuation. The presence and size of rectocoele or intussusception was unrelated to voiding of paste or balloon. An independent linear combination of pelvic floor descent and evacuation time on proctography correctly predicted maximum intrarectal pressure in 74% of cases. No patient with both prolonged evacuation and reduced pelvic floor descent on proctography could void the balloon, as maximum intrarectal pressure was reduced in this group. A prolonged evacuation time on proctography, in combination with reduced pelvic floor descent, suggests defecatory disorder may be caused by inability to raise intrarectal pressure. A diagnosis of anismus should not be made on proctography solely on the basis of incomplete/prolonged evacuation, as this may simply reflect inadequate straining.
"Alternative" cigarettes are no safer than conventional brands, report says
Authors: D. Spurgeon
Journal: BMJ (2002)

Alternative and “additive free” cigarettes, which are increasingly popular with North American adolescents, deliver substantial amounts of nicotine and other toxic components of tobacco smoke, contrary to common perceptions.

That is the finding of a study published in the December issue of Nicotine and Tobacco Research (2002;4:485-90). Lead researcher Wallace Pickworth, of the US National Institute of Drug Abuse, said that adolescents' use of alternative cigarettes, such as clove cigarettes, additive free cigarettes, and “bidis”—a type of leaf wrapped, unfiltered cigarette popular among poor people in India but increasingly fashionable among US teenagers—has increased.

The report says, …
Myocardial Perfusion in Acute Coronary Syndrome
Authors: Jörg Horcher, Rudolf Blasini, Stefan Martinoff, Markus Schwaiger, Albert Schömig, Christian Firschke
Journal: Circulation (1999)

V enous myocardial contrast echocardiography is a new method for myocardial perfusion imaging.It has been shown to accurately evaluate risk area and infarct size in the experimental setting of acute myocardial infarction and has recently become clinically available.We used this method to assess myocardial salvage after coronary reperfusion in a patient with acute coronary syndrome.A 68-year-old man with known single-vessel coronary artery disease presented with 6 hours of moderate chest pain typical of unstable angina.Four years earlier, a percutaneous transluminal coronary angioplasty of the left anterior descending coronary artery had been performed; the patient was asymptomatic throughout the following years.On admission, the 12-lead ECG showed atrial fibrillation and descending ST-segment depression up to 0.25 mV in leads V 3 through V 6 .Cardiac enzymes, including troponin I, were normal at that time.After medical treatment with heparin, nitroglycerin,
P1-02-06: Silencing of IGF-1R Has Paradoxical Effects in Triple Negative Breast Cancer Phenotypes.
Authors: LD Taliaferro-Smith, EM Oberlick, T Liu, C Eggers, ER Kline, GPC Nagaraju, A Marcus, R O'Regan
Journal: Cancer Research (2011)

Abstract Background: Triple negative (TN) breast cancers are a heterogeneous group of breast cancers with a poor prognosis in part due to a lack of effective targeted agents. Insulin-like growth factor-1 receptor (IGF-1R) has been shown to play a role in breast cancer cell proliferation, adhesion, invasion, and migration and is overexpressed in more than a third of TN breast tumors. We hypothesized that IGF-1R could be a therapeutic target for a subset of TN breast cancers. Methods: We evaluated the effects of IGF-1R silencing on the metastatic properties of TN breast cancer cells by knock down in two morphologically distinct TN breast cancer cell lines using shRNA lentiviral techniques. Reverse-transcription polymerase chain reaction (RT-PCR) and immunoblotting were used to detect mRNA and protein expression levels, respectively, of IGF-1R signaling molecules. Anchorage-dependent growth and Matrigel chamber assays were performed to assess the effects of IGF-1R silencing on colony formation and invasion of TN breast cancer cells, respectively; wound-healing and spheroid migration were also performed to assess the effects of IGF-1R inhibition on TN breast cancer cell motility. Results: Stably transfected mesenchymal MDA-MB-231 TN cells showed effective downregulation of IGF-1R protein expression, which resulted in mesenchymal-to-epithelial transition (MET), confirmed by upregulation of the epithelial marker E-cadherin and downregulation of the mesenchymal marker vimentin. Importantly, this MET resulted in reduced colony formation (p&amp;lt;0.0042) and cell motility and dramatically reduced invasion (p&amp;lt;0.0001). Conversely, silencing of IGF-1R in epithelial MDA-MB-468 TN cells induced epithelial-to-mesenchymal transition (EMT), confirmed by downregulation of E-cadherin and upregulation of vimentin expression, with resultant increased colony formation (p&amp;lt;0.006), cell motility, and invasion (p&amp;lt;0.0001). Conclusion: Collectively, these results demonstrate a paradoxical effect of targeting IGF-1R in TN breast cancers of mesenchymal and epithelial origin. Targeting IGF-1R in TN breast cancers with a mesenchymal phenotype decreases invasion and metastatic potential. In contrast, targeting IGF-1R in TN breast cancers with an epithelial phenotype could have potentially detrimental effects. Our data suggest that IGF-1R inhibition should be explored as a therapeutic modality in TN breast cancers with a mesenchymal phenotype. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-02-06.
24 HIGH MFI PREFORMED CLASS II DONOR SPECIFIC ANTIBODIES ACCELERATE FIBROSIS AND INCREASE MORTALITY AFTER LIVER TRANSPLANT IN HCV-INFECTED PATIENTS
Authors: J.G. O'Leary, H. Kaneku, L.W. Jennings, B.M. Susskind, P.I. Terasaki, G.B. Klintmalm
Journal: Journal of Hepatology (2013)
Site-Dependent Intra-Atrial Conduction Delay
Authors: Panos Papageorgiou, Kevin Monahan, Noel G. Boyle, Mark J. Seifert, Philippa Beswick, Joseph Zebede, Laurence M. Epstein, Mark E. Josephson
Journal: Circulation (1996)

Atrial dysrhythmia patients have exaggerated intra-atrial conduction delays and prolonged relative refractoriness in response to atrial premature depolarizations (APDs). Furthermore, atrial fibrillation (AF) is more readily inducible by APDs from the high right atrium (HRA) than the coronary sinus (CS). In this study, we postulated that site-specific intra-atrial conduction delays can explain why AF is initiated more from the HRA than from the CS.We examined 17 patients (age, 49 +/- 22 years) without a history of atrial flutter, AF, or structural heart disease. Programmed stimulation was carried out from the HRA and distal CS, and bipolar recordings were made at the HRA, His bundle, posterior triangle of Koch, and CS. More prolongations in conduction and relative refractoriness in all intra-atrial sites were observed during HRA than CS APDs. AF was induced in 8 patients after HRA and not CS stimulation. During HRA stimulation, patients with AF inducibility exhibited significant prolongation of conduction to the posterior triangle of Koch and marked broadening of the posterior triangle of Koch electrogram compared with CS stimulation. In patients without AF inducibility, the posterior triangle of Koch electrogram width was the same during HRA and CS stimulation.The existence of site-dependent intra-atrial conduction delays and site-dependent dispersion of refractoriness appears to be a common property of the atrial myocardium and does not necessarily forecast AF inducibility. However, the presence of nonuniform anisotropic characteristics of the posterior triangle of Koch may be critical for AF induction.
Cancer “tsar” faces parliamentary group on waiting time targets
Authors: Tiago Villanueva
Journal: BMJ (2004)

The current health service infrastructure for cancer is insufficient for waiting time targets to be met, said Professor Mike Richards, the government's national cancer director, who was called to a parliamentary inquiry last week to give evidence on cancer services.

The inquiry, conducted by the All Party Parliamentary Group on Cancer, is investigating how national standards aimed at ending regional variations in cancer services can be met after the government announced in July 2003 that it was to devolve decision making and 75% of the NHS budget to local NHS bodies.

Professor Richards said that according to the three year progress report on the implementation of the NHS cancer plan, published in October 2003, there had been an unprecedented investment in facilities such as computed tomography scanners, magnetic resonance imaging scanners, and linear accelerators but …
The tantalizing triplet of pulmonary hypertension—BMP receptors, serotonin receptors, and angiopoietins
Authors: O Eickelberg
Journal: Cardiovascular Research (2003)

See article by Blanpain et al. (pages 518–528) in this issue. 

Not many diseases have attracted as much attention by the basic and clinical research community during the last several years as has idiopathic pulmonary arterial hypertension (IPAH, formerly primary pulmonary hypertension). IPAH is a severe and progressive disease localized exclusively to the lung, which exhibits an abnormally elevated precapillary pulmonary vascular resistance due to vasoconstriction and remodelling of the pulmonary vascular system. The underlying histological abnormalities consistently found in severe disease are obstructive and concentric lesions of small pulmonary resistance arterioles, which lead to an elevated pulmonary arterial pressure of >25 mm Hg at rest or >30 mm Hg during exercise. These lesions are thought to be due to enhanced proliferation of endothelial and/or smooth muscle cells or to the local transformation of quiescent fibroblasts into smooth muscle cells. The elevated pulmonary vascular pressure leads to progressive right heart hypertrophy and eventual failure, often resulting in death if undiagnosed and untreated [1,2].

Although IPAH mostly occurs as a sporadic disease, a subset of patients was identified as early as 1954 who exhibited a family history of the disease [3]. This led to the identification of several cases of familial IPAH [4], which now represents an autosomal dominant disorder with incomplete penetrance. For a long time, familial IPAH was considered a mysteriously devastating disease of unknown etiology. However, recent genetic linkage studies have revealed at least one definite PPH1 locus on chromosome 2q31–32 [5,6]. In 2000, positional cloning revealed that the causative factor for familial IPAH within the PPH1 locus was BMPR2 , the gene encoding bone morphogenetic protein receptor (BMPR) II [7,8]. Direct sequence analysis has identified multiple … 

*Corresponding author. Tel.: +49-641-9942300; fax: +49-641-9942309. Email address: oliver.eickelberg{at}innere.med.uni-giessen.de
Changing the pattern out of hours: a survey of general practice cooperatives
Authors: L. Jessopp, I. Beck, L. Hollins, C. Shipman, M. Reynolds, J. Dale
Journal: BMJ (1997)

Objective: To evaluate an out of hours cooperative of general practitioners compared with a deputising service.Design: Observational study of two services in overlapping geographical areas.Setting: A general practice cooperative in Kensington, Chelsea, and Westminster and a deputising service operating in that area and the neighbouring area of Brent and Harrow.Subjects: All patients contacting a doctor at either service in an eight week period beginning 1 September 1995.Main outcome measures: Patients' age and sex; rates of home visiting, telephone advice, and attendance at a primary centre; hospital admission rates; prescribing rates; times of patient calls; and response times.Results: Data were collected on 5812 patient contacts.Doctors from the cooperative visited 32.0% (1253/ 3920) of patients, offered telephone advice to 57.8% (2267), and saw 7.1% (278) of patients at the primary care centre.By contrast, the deputising service visited 76.3% (1444/1892) of patients and gave telephone advice to 19.3% (365).Doctors from the cooperative prescribed drugs to fewer patients (37.6%; 1473/3915) than did the deputising service (51.7%; 941/1821) (odds ratio 0.56 (95% confidence interval 0.50 to 0.63) adjusted for age and sex) and admitted 8.7% (339/ 3888) of patients to hospital compared with 6.8% (128/1889) from the deputising service (odds ratio 1.30 (1.05 to 1.61) adjusted for age and sex).Response times for the deputising service were faster (median time to visit 65 minutes) than for the cooperative (median time to visit 75 minutes) but the time to first contact with a doctor was shorter for the cooperative because most people initially received telephone advice. Conclusions:The cooperative in this study dealt with patient contacts very differently from the way the deputising service dealt with contacts, fewer patients being visited and fewer receiving prescriptions.The data presented enable other out of hours services to compare their own performance using a standard data collection and analysis program.
Correlation of 15-prostagladin dehydrogenase expression with clinicopathological factors and survival rate in gastric adenocarcinoma
Authors: Sang Hyuk Seo, Mi Seon Kang, Kwang Hee Kim, Min Sung An, Tae Kwun Ha, Ki Beom Bae, Min Kyung Oh, Chang Soo Choi, Sang Hoon Oh, Young Kil Choi
Journal: International Journal of Surgery (2015)
Bacterial contamination of the small intestine is an important cause of occult malabsorption in the elderly.
Authors: A McEvoy, J Dutton, O F James
Journal: BMJ (1983)

A study was conducted to examine the contribution that occult malabsorption makes to malnutrition among elderly patients admitted to an acute geriatric ward. Malnutrition was defined by anthropometric, haematological, and biochemical measurements. Out of 490 patients, 55--many of whom had presented with non-gastrointestinal symptoms--were found to be malnourished. In 31 poor diet alone was probably the cause, but in the remaining 24 patients previously unrecognised malabsorption was detected. Of these patients, 17 were found to have bacterial contamination of the small bowel (nine with duodenojejunal diverticula, four after gastric surgery, and four diagnosed as contamination with "no sump"). In 10 patients contamination was confirmed by culture of intestinal juice: Escherichia coli was predominant in nine cases, and anaerobic organisms in one. Small bowel bacterial overgrowth without a "blind loop" or obvious underlying cause has not previously been fully proved in the elderly. Coeliac disease was detected in two patients, and chronic pancreatitis in two. Occult malabsorption is an important cause of malnutrition in the elderly. Such malnutrition not infrequently occurs in geriatric patients presenting to hospital with non-specific symptoms of physical deterioration.
Test Your Knowledge: Ten Questions about Stroke
Authors: Gavin Yamey
Journal: PLoS Medicine (2005)

Quiz Question 1. Roughly what proportion of all strokes are ischemic (rather than hemorrhagic)?25% 50% 75% 95% Question 2. Roughly what proportion of ischemic strokes are due to carotid stenosis?5% 20% 50% 75% Question 3. Roughly how many people worldwide each year experience a stroke?15 million 25 million 35 million Question 4. Roughly how many deaths worldwide are due to stroke each year?1.5 million 5.5 million 10.5 million Question 5.In people who have had a stroke or transient ischemic attack, what is the subsequent risk of stroke?About 30% of patients will have a stroke in the fi rst year, and about 15% each year thereafter About 10% of patients will have a stroke in the fi rst year, and about 5% each year thereafter About 2% of patients will have a stroke in the fi rst year, and about 1% each year thereafter
NKX3.1 Homeodomain Protein Binds to Topoisomerase I and Enhances Its Activity
Authors: Cai Bowen, August Stuart, Jeong-Ho Ju, Jenny Tuan, Josip Blonder, Thomas P. Conrads, Timothy D. Veenstra, Edward P. Gelmann
Journal: Cancer Research (2007)

Abstract The prostate-specific homeodomain protein NKX3.1 is a tumor suppressor that is commonly down-regulated in human prostate cancer. Using an NKX3.1 affinity column, we isolated topoisomerase I (Topo I) from a PC-3 prostate cancer cell extract. Topo I is a class 1B DNA-resolving enzyme that is ubiquitously expressed in higher organisms and many prokaryotes. NKX3.1 interacts with Topo I to enhance formation of the Topo I-DNA complex and to increase Topo I cleavage of DNA. The two proteins interacted in affinity pull-down experiments in the presence of either DNase or RNase. The NKX3.1 homeodomain was essential, but not sufficient, for the interaction with Topo I. NKX3.1 binding to Topo I occurred independently of the Topo I NH2-terminal domain. The binding of equimolar amounts of Topo I to NKX3.1 caused displacement of NKX3.1 from its cognate DNA recognition sequence. Topo I activity in prostates of Nkx3.1+/− and Nkx3.1−/− mice was reduced compared with wild-type mice, whereas Topo I activity in livers, where no NKX3.1 is expressed, was independent of Nkx3.1 genotype. Endogenous Topo I and NKX3.1 could be coimmunoprecipitated from LNCaP cells, where NKX3.1 and Topo I were found to colocalize in the nucleus and comigrate within the nucleus in response to either γ-irradiation or mitomycin C exposure, two DNA-damaging agents. This is the first report that a homeodomain protein can modify the activity of Topo I and may have implications for organ-specific DNA replication, transcription, or DNA repair. [Cancer Res 2007;67(2):455–64]
Conn's Last Words on Conn's Sign
Authors: MICHAEL A. LACOMBE
Journal: Annals of Internal Medicine (1971)

Letters, Comments, and Corrections1 December 1971Conn's Last Words on Conn's SignMICHAEL A. LACOMBE, M.D.MICHAEL A. LACOMBE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-75-6-976_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: With regard to the letter "Conn's Sign or Duck?" (Ann Intern Med75:482, 1971), we have observed several cases of ascitic cirrhotic patients with scrotal edema, abducted legs, and a urinal in place, representing the rather unusual association of Conn's sign with pseudo-Conn's sign. We also had the good fortune of studying a single case in which, when abducted legs were spotted, the bed sheet was lifted, and neither ascites, nor scrotal edema, nor a urinal was present. Close questioning revealed that the patient had just finished urinating, the nurse had removed the urinal, and the patient... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Division of Eponymic Medicine School of Medicine and Dentistry and Strong Memorial Hospital The University of Rochester Rochester, N.Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPseudopseudo-Darnell's SignMICHAEL A. LACOMBE, M.D. 1 December 1971Volume 75, Issue 6Page: 976-977KeywordsAscitesEdemaNursesUrination ePublished: 1 December 2008 Issue Published: 1 December 1971 PDF downloadLoading ...
136 THE A736V TMPRSS6 POLYMORPHISM IS ASSOCIATED WITH THE PENETRANCE OF HEREDITARY HEMOCHROMATOSIS AND HEPATOCELLULAR CARCINOMA IN C282Y +/+ PATIENTS
Authors: L. Valenti, A.L. Fracanzani, R. Rametta, G. Soverini, S. Pelusi, P. Dongiovanni, S. Fargion
Journal: Journal of Hepatology (2012)
Low bioavailability as a cause of apparent failure of dihydroergotamine in orthostatic hypotension.
Authors: I N Olver, G L Jennings, A Bobik, M Esler
Journal: BMJ (1980)

properties at high blood concentrations.MacLeod and Lamberts3 have shown the dopamine agonist effects of high concentrations of haloperidol and pimozide on prolactin release.Seeman4 has shown that very high concentrations of some antipsychotic drugs may enhance presynaptic release of neurotransmitters, including dopamine.Altematively, at high concentrations of antipsychotic drugs maximal dopaminergic blockade may occur.Additional dosage increments would not produce further dopamine blockade, but other pharma- cological effects, such as anticholinergic activity, might continue to increase and might be responsible for the presentations described.Toxic psychoses have been associated with high doses of anticholinergic drugs,5 usually combined with moderate doses of antipsychotic drugs.The episodes reported in these studies also appear to have been characterised by excitement and aggression, as in our cases.Requests for reprints to Dr Bridges.1 Barnes TRE, Roy DH, Gaind R. Open study to determine appropriate maintenance dosage of pimozide in patients with chronic schizophrenia.
Genealogies and weak purifying selection
Authors: M. Przeworski, B. Charlesworth, J. D. Wall
Journal: Molecular Biology and Evolution (1999)

The assumption that selection alters the genealogical tree of a sample of alleles from a population relative to the neutral expectation underlies several "tests of neutrality." Two recent papers have studied the effect of purifying selection; their suggestive but incomplete results indicate that, in the single site case, the shape of a gene genealogy for a locus may differ only from the neutral expectation. We verify this finding for weak selection using the "ancestral selection graph." We consider a wider range of models, including both a four-allele single-site model and an infinite-sites model. Our results confirm the previous claim for the symmetric-mutation single site model. We emphasize, however, that a neutral-seeming genealogy is consistent with detectable effects of selection on the distribution of allele frequences within the sample. With selection operating, the information about a sample cannot be reduced to the genealogy. As a result, a distinction needs to be made between the selected sites themselves, for which the genealogy offers insufficient information, and linked neutral variation. This distinction seems to have been overlooked in previous papers, yet it has significant implications for the interpretation of data on DNA sequence variation. In particular, it predicts that under purifying selection, the frequency spectrum of neutral mutations will not reflect the skew toward rare polymorphisms at replacement sites even if there is no recombination between them. We caution, however, that the effect of weak selection on the genealogy is specific to the model; a (more realistic) model of multiple linked sites could lead to a more distorted genealogy than is observed for a single site.