tbuckley/cabot-search huggingface dataset:
Ethnic differences in mortality from ischaemic heart disease and cerebrovascular disease in England and Wales.
Authors: R Balarajan
Journal: BMJ (1991)

To examine mortality from ischaemic heart disease and cerebrovascular disease in England and Wales by country of birth of the deceased.Standardised mortality ratios were computed by country of birth groups for ischaemic heart disease and cerebrovascular disease for 1979-83 and 1970-2 by using the five year age-sex specific rates for England and Wales for 1979-83 as standard.England and Wales 1970-2 and 1979-83.In 1979-83 mortality from ischaemic heart disease was highest in men and women born in the Indian subcontinent (standardised mortality ratio 136 and 146 respectively). Young Indian men suffered the greatest excess (313 at ages 20-29). Other groups with raised mortality included Irish, Scottish, and Polish born immigrants. Those born in the Caribbean, the old Commonwealth, west Europe, and the United States had low death rates. In England and Wales mortality from ischaemic heart disease declined by 5% in men and 1% in women between 1970-2 and 1979-83, with greatest percentage declines in immigrants born in the United States, South Africa, the old Commonwealth, the Caribbean, and France. immigrant groups with raised mortality in the earlier period showed little improvement, and mortality from ischaemic heart disease increased among Indians (6% in men and 13% in women). In 1979-83 mortality from cerebrovascular disease was highest in Caribbeans (standardised mortality ratios 176 in men and 210 in women), followed by Africans, Indians, and Irish. Rates were low in west Europeans. Mortality from stroke declined by 28% overall in this period, a rate of decline shared by most groups. Men from the Indian subcontinent showed a decline of only 3%.In the 1980s mortality from ischaemic heart disease and cerebrovascular disease differed significantly between ethnic groups in England and Wales. In general, ethnic groups that experienced lower mortality from ischaemic heart disease in the 1970s showed the greatest improvement over the following decade.
Propionyl-L-carnitine prevents early graft dysfunction in allogeneic rat kidney transplantation
Authors: Nadia Azzollini, Daniela Cugini, Paola Cassis, Anna Pezzotta, Elena Gagliardini, Mauro Abbate, Arduino Arduini, Alessandro Peschechera, Giuseppe Remuzzi, Marina Noris
Journal: Kidney International (2008)
As different as Venus and Mars: time to distinguish efficacy (can it work?) from effectiveness (does it work?)
Authors: Karim M Khan, Hashel Al Tunaiji
Journal: British Journal of Sports Medicine (2011)

Although the news has not yet hit the New England Journal of Medicine, there is an epidemic sweeping North America.You can read more about it on the BJSM blog (http://tiny.cc/00vmq)but it kills as many people in USA as do smoking, diabetes and obesity combined.NIH Nightmare.Yes, this worse-than-Ebola disease -smokadiabesity -kills a frightening 14% of Americans.Fortunately, Professor Steven Blair had a premonition about this epidemic, so he already has 20-year prospective data comparing deaths from the new epidemic and from low fi tness (fi gure 2). 1 Astonishingly, low fi tness still kills more Americans (16-18%) than even rampant 'smokadiabesity'.
Dominant-Negative but not Gain-of-Function Effects of a <i>p53.R270H</i> Mutation in Mouse Epithelium Tissue after DNA Damage
Authors: Susan W.P. Wijnhoven, Ewoud N. Speksnijder, Xiaoling Liu, Edwin Zwart, Conny Th. M. vanOostrom, Rudolf B. Beems, Esther M. Hoogervorst, Mirjam M. Schaap, Laura D. Attardi, Tyler Jacks, Harry van Steeg, Jos Jonkers, Annemieke de Vries
Journal: Cancer Research (2007)

Abstract p53 alterations in human tumors often involve missense mutations that may confer dominant-negative or gain-of-function properties. Dominant-negative effects result in inactivation of wild-type p53 protein in heterozygous mutant cells and as such in a p53 null phenotype. Gain-of-function effects can directly promote tumor development or metastasis through antiapoptotic mechanisms or transcriptional activation of (onco)genes. Here, we show, using conditional mouse technology, that epithelium-specific heterozygous expression of mutant p53 (i.e., the p53.R270H mutation that is equivalent to the human hotspot R273H) results in an increased incidence of spontaneous and UVB-induced skin tumors. Expression of p53.R270H exerted dominant-negative effects on latency, multiplicity, and progression status of UVB-induced but not spontaneous tumors. Surprisingly, gain-of-function properties of p53.R270H were not detected in skin epithelium. Apparently, dominant-negative and gain-of-function effects of mutant p53 are highly tissue specific and become most manifest upon stabilization of p53 after DNA damage. [Cancer Res 2007;67(10):4648–56]
Expression of two human skeletal calcitonin receptor isoforms cloned from a giant cell tumor of bone. The first intracellular domain modulates ligand binding and signal transduction.
Authors: A H Gorn, S M Rudolph, M R Flannery, C C Morton, S Weremowicz, T Z Wang, S M Krane, S R Goldring
Journal: Journal of Clinical Investigation (1995)

Two distinct calcitonin (CT) receptor (CTR)-encoding cDNAs (designated GC-2 and GC-10) were cloned and characterized from giant cell tumor of bone (GCT). Both GC-2 and GC-10 differ structurally from the human ovarian cell CTR (o-hCTR) that we cloned previously, but differ from each other only by the presence (GC-10) or absence (GC-2) of a predicted 16-amino acid insert in the putative first intracellular domain. Expression of all three CTR isoforms in COS cells demonstrated that GC-2 has a lower binding affinity for salmon (s) CT (Kd approximately 15 nM) than GC-10 or o-hCTR (Kd approximately 1.5 nM). Maximal stimulatory concentrations of CT resulted in a mean accumulation of cAMP in GC-2 transfected cells that was greater than eight times higher than in cells transfected with GC-10 after normalizing for the number of receptor-expressing cells. The marked difference in maximal cAMP response was also apparent after normalizing for receptor number. GC-2 also demonstrated a more potent ligand-mediated cAMP response compared with GC-10 for both human (h) and sCT (the EC50 values for GC-2 were approximately 0.2 nM for sCT and approximately 2 nM for hCT; EC50 values for GC-10 were approximately 6 nM for sCT and approximately 25 nM for hCT). Reverse transcriptase PCR of GCT RNA indicated that GC-2 transcripts are more abundant than those encoding for GC-10. In situ hybridization on GCT tissue sections demonstrated CTR mRNA expression in osteoclast-like cells. We localized the human CTR gene to chromosome 7 in band q22. The distinct functional characteristics of GC-2 and GC-10, which differ in structure only in the first intracellular domain, indicate that the first intracellular domain of the CTR plays a previously unidentified role in modulating ligand binding and signal transduction via the G protein/adenylate cyclase system.
Multiple linear lichen planus in the lines of Blaschko
Authors: C. C. LONG, A. Y. FINLAY
Journal: British Journal of Dermatology (1996)

The lines of Blaschko describe a distribution pattern which may represent embryological development pathways. The distribution may occasionally be followed by some skin disorders. We report a patient who had multiple lesions of linear lichen planus which followed Blaschko's lines. There were multiple streaks affecting several different areas of the body.
Severe asthma is an epithelial disease
Authors: P. Chanez
Journal: European Respiratory Journal (2005)

Asthma is an important, clinically prevalent disease worldwide. Despite a better knowledge on the pathogenesis, the mechanisms underlying the induction and persistence of the disease are largely unknown. It is now accepted that airway inflammation and structural changes of the bronchi are important features. The relationships between those structural changes and clinical and functional abnormalities clearly deserved further investigations. These findings led to the reinforcement of the use of inhaled corticosteroids as the pivotal treatment for asthma. Nevertheless, there are still patients who have persistent symptoms, altered lung function and a high rate of exacerbations, despite long-term specialist follow-up and continuous optimal treatment. These severe patients have a major handicap in their daily life and are responsible for most of the costs created by asthma 1. Therefore, it is of major importance to better understand the mechanisms leading to this severe phenotype.

Almost one century ago, Ellis 2 highlighted that the pathology of asthma could be investigated by examining sputum from living patients or the lungs of patients who die during an attack. From these sources, the role of bronchial epithelium was clarified by describing elongated epithelial cells in the sputum and the presence of abnormalities of the pseudo-stratified and ciliated epithelium in most fatal cases, albeit it varied considerably as regards location and extent 2. The role played by …
Importance of the Design of an Exercise Protocol in the Evaluation of Patients with Angina Pectoris
Authors: DAVID R. REDWOOD, DOUGLAS R. ROSING, ROBERT E. GOLDSTEIN, G. DAVID BEISER, STEPHEN E. EPSTEIN
Journal: Circulation (1971)

The severity of angina and the effects of therapeutic interventions in patients with coronary artery disease have been assessed by determining changes in both exercise performance and the triple product (TP) of heart rate, systolic pressure, and ejection time occurring at angina. However, the validity of conclusions based on such changes is uncertain since the effects of different exercise protocols on these variables have not been determined. Twelve patients with angina were studied during upright bicycle exercise; repeated bouts of exercise using a standard protocol of 20-w increments every three minutes produced no consistent changes in TP at angina. When exercise began 20 to 60 w above the work load of the standard protocol that produced angina, exercise capacity was reduced (average 1'40'' vs. 4'40'', P &lt; 0.001), and triple product at angina exceeded control anginal values (average 4,840 vs. 4,150, P &lt; 0.001). In the control studies nitroglycerin (TNG) and carotid sinus nerve stimulation (CSNS) enabled patients to exercise to a higher level, although the triple product at angina was unaltered. However, at the higher work load TNG and CSNS exerted only minimal effects on exercise capacity, indicating that if the work load is excessive, a reduction in myocardial oxygen consumption produced by a therapeutic intervention may be comparatively minor so that a potentially salutary effect would be masked. We conclude that work loads causing angina in less than three minutes cannot reliably be used for studying the effects of therapy. However, if progressive work loads are chosen which cause angina in the control studies in three to six minutes, exercise capacity and triple product at angina provide important information about the efficacy and mechanism of action of a therapeutic intervention.
Obesity is associated with an increased risk of monoclonal gammopathy of undetermined significance among black and white women
Authors: Ola Landgren, S. Vincent Rajkumar, Ruth M. Pfeiffer, Robert A. Kyle, Jerry A. Katzmann, Angela Dispenzieri, Qiuyin Cai, Lynn R. Goldin, Neil E. Caporaso, Joseph F. Fraumeni, William J. Blot, Lisa B. Signorello
Journal: Blood (2010)
US bill would force FDA to withdraw approval of new pain drug Zohydro
Authors: M. McCarthy
Journal: BMJ (2014)

Joe Manchin, a Democrat senator from West Virginia, introduced a bill on Thursday 13 March that would force the US Food and Drug Administration to withdraw its approval of the controversial opioid pain drug Zohydro ER.

The FDA’s decision to approve the drug—a high dose, long acting formulation of hydrocodone bitartrate—has been sharply criticized by addiction experts and law enforcement officials, who warned that its approval would lead to a sharp rise in drug addiction and deaths from overdose.1 …
Regulation of arachidonic acid, eicosanoid, and phospholipase A2 levels in murine mast cells by recombinant stem cell factor.
Authors: A N Fonteh, J M Samet, F H Chilton
Journal: Journal of Clinical Investigation (1995)

The current study evaluates the capacity of recombinant rat stem cell factor (rrSCF) to regulate enzymes that control AA release and eicosanoid generation in mouse bone marrow-derived mast cells (BMMCs). Initial studies indicated that rrSCF provided for 24 h inhibited the release of AA into supernatant fluids of antigen- and ionophore A23187-stimulated BMMCs. Agonist-induced increases in cellular levels of AA were also inhibited, albeit to a lesser degree by rrSCF. To determine the inhibitory mechanism, several steps (e.g., mobilization of cytosolic calcium, release of BMMC granules, and regulation of phospholipase A2 [PLA2] activity) that could influence AA release were measured in rrSCF-treated cells. rrSCF did not alter the capacity of BMMCs to mobilize cytosolic calcium or release histamine in response to antigen and ionophore. BMMCs released large amounts of PLA2 with characteristics of the group II family in response to antigen and ionophore A23187. rrSCF treatment of BMMCs reduced the secretion of this PLA2 activity by BMMCs. Partial purification of acid-extractable PLA2 from rrSCF-treated and untreated BMMCs suggested that rrSCF decreased the quantity of acid-stable PLA2 within the cells. In contrast to group II PLA2, the quantity of cPLA2 (as determined by Western blot analysis) increased in response to rrSCF. To assess the ramifications of rrSCF-induced reductions in AA and group II PLA2, eicosanoid formation was measured in antigen- and ionophore-stimulated BMMCs, rrSCF-inhibited (100 ng/ml, 24 h) prostaglandin D2 (PGD2), thromboxane B2, and leukotriene B4 by 48.4 +/- 7.7%, 61.1 +/- 10.0% AND 38.1 +/- 3.6%, respectively, in antigen-stimulated cells. Similar patterns of inhibition were observed in ionophore-stimulated BMMCs. The addition of a group I PLA2 or exogenous AA to BMMCs reversed the inhibition of eicosanoid generation induced by rrSCF. Together, these data indicate that rrSCF differentially regulates group II and cytosolic PLA2 activities in BMMCs. The resultant reductions in eicosanoid generation suggest that group II PLA2 provides a portion of AA that is used for eicosanoid biosynthesis by BMMCs.
Cytochrome P450 2A6: a new hepatic autoantigen in patients with chronic hepatitis C virus infection
Authors: Georgios N Dalekos, Petra Obermayer-Straub, Moritz Bartels, Takashi Maeda, Anne Kayser, Sabine Braun, Stephanie Loges, Eleonore Schmidt, M.Eric Gershwin, Michael P Manns
Journal: Journal of Hepatology (2003)
Enhanced expression of heparin-binding EGF-like growth factor and its receptor in hypertrophied left ventricle of spontaneously hypertensive rats
Authors: T Fujino
Journal: Cardiovascular Research (1998)

Although heparin-binding epidermal growth factor-like growth factor (HB-EGF) is thought to produce hypertrophy in isolated cardiomyocytes via an autocrine mechanism, the pathophysiological role of HB-EGF, in myocardial hypertrophy in vivo, is not yet known. To investigate the involvement of HB-EGF in cardiac remodeling associated with hypertension in vivo, we assayed the expression of HB-EGF mRNA and protein in the left ventricle (LV) during the development of left ventricular hypertrophy in spontaneously hypertensive rats (SHR).Prior to sacrifice and assay of HB-EGF and EGF-receptor (EGF-R) mRNA, morphologic and hemodynamic variables were measured in SHR and in age-matched Wistar Kyoto rats (WKY). At 5, 9 and 12 weeks of age, rats were killed, their hearts were removed, and the expression of HB-EGF and EGF-R mRNA and protein were measured. In addition, SHR and WKY were treated with enalapril, atenolol, or both for 4 weeks.In untreated SHR, double products (i.e. systolic blood pressure (sBP) multiplied by heart rate (HR), an index of mechanical load, peaked at 9 weeks. Expression of HB-EGF mRNA was also observed to peak in these animals at 9 weeks, while expression of EGF-R mRNA increased from 5 to 9 weeks, but remained constant thereafter. In untreated WKY, double products and EGF-R mRNA expression did not change over time, whereas the level of HB-EGF message increased gradually. Antibody to HB-EGF reacted primarily with myocyte membranes in SHR, whereas antibody to EGF-R reacted mainly with interstitial cells in these animals. The angiotensin-converting enzyme inhibitor, enalapril, markedly decreased sBP in SHR, whereas the beta 1-adrenoreceptor antagonist, atenolol, significantly decreased HR. While neither alone affected the expression of HB-EGF mRNA, their combination significantly reduced the expression of HB-EGF mRNA, as well as double products, in these rats, but had no effect on expression of EGF-R mRNA.The enhanced expression of HB-EGF mRNA and protein in LV of SHR suggest that this growth factor may play an important role during the early development of LV hypertrophy and cardiac fibrosis in SHR. The association between double products and HB-EGF expression suggest that the latter may be induced by increased mechanical load and may contribute, in turn, to cardiac remodeling.
Tolerance to Oxprenolol
Authors: Zwi Weiss
Journal: JAMA (1985)

<h3>To the Editor.—</h3> Because there is a high incidence of noncompliance in hypertensive patients,<sup>1</sup>periodic checks of absorption and blood levels of slow-release oxprenolol were carried out at our hypertension clinic after oral administration of the therapeutic dose prescribed to individual patients. Blood samples were drawn at 30-minute intervals for up to five hours. Blood pressure and basal heart rate were recorded at the time the blood samples were taken. Oxprenolol plasma levels were determined by means of high-pressure liquid chromatography using a flow-rate and solvent programmable chromatographic pump (5020 Varian), reverse-phase Spherisorb octadecylsilane column (particle size, 10 μm), and a double-beam, flow-through ultraviolet detector (Varian Varichrom) (M. Mines, MSc, unpublished data, February 1982). Tolerance to oxprenolol was shown to have developed in two patients. <h3>Report of Cases.—Patient 1.—</h3> In 1974, 20 mg of oxprenolol, four tablets per day, and diuretics were prescribed to a 56-year-old woman
The physician’s voice in the health care debate
Authors: Jonathan A. Epstein, Laurence A. Turka, Morris Birnbaum, Gary Koretzky
Journal: Journal of Clinical Investigation (2009)

Physicians in the United States have a unique appreciation of the tremendous successes and even greater potential of our health care system, yet we also endure firsthand its woeful deficiencies. In the ongoing debate about how to improve the current health care structure in the United States, our individual voices have been all too quiet. No single health care organization, nor its spokesmen, speaks for the broad range of physicians’ opinions. Rather, doctors must make every effort, and indeed have an obligation, to speak forcefully as informed participants in this important process.
High rates of hepatocellular carcinoma in cirrhotic patients with high liver cell proliferative activity
Authors: Maria Francesca Donato, Eliana Arosio, Ersilio Del Ninno, Guido Ronchi, Pietro Lampertico, Alberto Morabito, Maria Rita Balestrieri, Massimo Colombo
Journal: Hepatology (2001)

The prevalence, risk factors, and clinical significance of high liver cell proliferative activity were investigated in 208 well-compensated cirrhotic patients (150 men; 50 years; 135 with chronic hepatitis C) who had been under prospective surveillance for hepatocellular carcinoma (HCC) with annual abdominal ultrasound (US) and serum α-fetoprotein (AFP) determination. Immunostaining for proliferating cell nuclear antigen (PCNA) was employed to assess liver cell proliferative activity in formalin-fixed, paraffin-embedded liver specimens. The percentage of reactive nuclei was calculated by a computer-assisted image analysis system. The overall PCNA labeling index (LI) ranged from 0.1% to 12.5% (mean, 2.1%), being significantly higher in the 50 patients who developed HCC during 88 ± 42 months of follow-up than in the 158 patients who remained cancer-free (3.6% ± 2.4% vs. 1.6% ± 1.5%; P &lt; .0001). By receiver operating curve (ROC), a 2.0% cut-off value of PCNA-LI discriminated between patients at high and low risk for developing cancer. By multivariate analysis, high histologic grading scores and gender were associated to PCNA LI &gt;2.0%. The yearly incidence of HCC was 5.2% for the 80 patients with PCNA-LI &gt;2.0% compared with 1.1% for the 128 with low PCNA-LI (relative risk, 4.90; 95% CI, 2.63-9.55). By multivariate analysis, PCNA-LI &gt;2.0% was the strongest independent predictor of cancer (hazard ratio, 5.49; 95% CI, 2.90-10.37). Overall, survival was significantly lower in patients with high liver cell proliferative activity rates than in those with low proliferative rates (10% vs. 75%; P &lt; .0001). In conclusion, development of HCC in patients with compensated cirrhosis seems to be reliably predicted by liver cell proliferation status. (Hepatology 2001;34:523-528.)
Angiotensin II amplification of alpha-adrenergic vasoconstriction: role of receptor reserve.
Authors: R E Purdy, M A Weber
Journal: Circulation Research (1988)

Angiotensin II (Ang II) is known to enhance the vasoconstrictor response to norepinephrine (NE). In the present study, this interaction was investigated using isolated rabbit femoral artery rings mounted in tissue baths for the measurement of isometric contraction. Exposure to 3 x 10(-10) M Ang II caused a contraction that was less than 5% of the maximal response to NE. In the presence of Ang II, the NE dose-response curve shifted to the left twofold and the maximal response was not changed. The calcium channel antagonist nifedipine, 1 x 10(-7) M, caused a modest inhibition of the response to NE in either the presence or absence of Ang II. In contrast, nifedipine abolished the leftward shift of the NE dose-response curve caused by Ang II. Femoral arteries were pretreated with benextramine to cause partial alpha-adrenoceptor inactivation. The maximal contractile response to NE in these tissues was between 20% and 40% of that in control vessels, indicating that alpha-adrenoceptor reserve had been eliminated. In benextramine-pretreated vessels, the presence of 3 x 10(-10) M Ang II caused a modest leftward shift of the NE dose-response curve but increased the maximal responses to all NE concentrations by 200% to 800%. Nifedipine caused a modest inhibition of the response to NE in the absence of Ang II. In contrast, the enhanced response to NE in the presence of Ang II was nearly abolished. These results support our conclusions that 1) Ang II enhances the vasoconstrictor response to alpha-adrenergic stimulation, 2) the magnitude of enhancement is greater under conditions of reduced alpha-receptor reserve, and 3) calcium channel activation plays a major role in the amplified response.
Regulation of lipoprotein lipase and hormone-sensitive lipase activity and gene expression in adipose and muscle tissue by growth hormone treatment during weight loss in obese patients
Authors: Bjørn Richelsen, Steen B. Pedersen, Kurt Kristensen, Jens D. Børglum, Helene Nørrelund, Jens S. Christiansen, Jens O.L. Jørgensen
Journal: Metabolism (2000)
Commentary: yet more to see down the bronchial tree?
Authors: M. R. Hetzel
Journal: Thorax (1996)

insertion is straightforward and minimally in- vasive,8 and the stent can be left in place long term without swallowing, voice, or coughing problems.Our patient had a major and sustained improvement of his lung function with disappearance of his airways obstruction.We believe that restoration of airflow was the major factor in this clinical improvement.He still has copious purulent secretions colonised by Pseudomonas due to bilateral bronchiectasis, but eliminates secretions easily and infection is no longer a problem.