tbuckley/cabot-search huggingface dataset:
Enhanced Sensitivity to Cytochrome <i>c</i>–Induced Apoptosis Mediated by PHAPI in Breast Cancer Cells
Authors: Zachary T. Schafer, Amanda B. Parrish, Kevin M. Wright, Seth S. Margolis, Jeffrey R. Marks, Mohanish Deshmukh, Sally Kornbluth
Journal: Cancer Research (2006)

Abstract Apoptotic signaling defects both promote tumorigenesis and confound chemotherapy. Typically, chemotherapeutics stimulate cytochrome c release to the cytoplasm, thereby activating the apoptosome. Although cancer cells can be refractory to cytochrome c release, many malignant cells also exhibit defects in cytochrome c–induced apoptosome activation, further promoting chemotherapeutic resistance. We have found that breast cancer cells display an unusual sensitivity to cytochrome c–induced apoptosis when compared with their normal counterparts. This sensitivity, not observed in other cancers, resulted from enhanced recruitment of caspase-9 to the Apaf-1 caspase recruitment domain. Augmented caspase activation was mediated by PHAPI, which is overexpressed in breast cancers. Furthermore, cytochrome c microinjection into mammary epithelial cells preferentially killed malignant cells, suggesting that this phenomenon might be exploited for chemotherapeutic purposes. (Cancer Res 2006; 66(4): 2210-8)
Giant Cell Carcinoma of the Liver: occurrence in a patient with ileal carcinoid, medullary breast carcinoma and pulmonary aspergillosis
Authors: D. C. Stolinsky, N. C. Sun
Journal: CA A Cancer Journal for Clinicians (1979)

Pure giant cell carcinoma of the liver is a rare tumor that is usually associated with cirrhosis. Its occurrence in a young woman without evidence of cirrhosis, and in association with two other uncommon tumors, is described in this report.
In vivo blood flow abnormalities in the transgenic knockout sickle cell mouse
Authors: Stephen H. Embury, Narla Mohandas, Chris Paszty, Philip Cooper, Anthony T.W. Cheung
Journal: Journal of Clinical Investigation (1999)

The accepted importance of circulatory impairment to sickle cell anemia remains to be verified by in vivo experimentation. Intravital microscopy studies of blood flow in patients are limited to circulations that can be viewed noninvasively and are restricted from deliberate perturbations of the circulation. Further knowledge of sickle blood flow abnormalities has awaited an animal model of human sickle cell disease. We compared blood flow in the mucosal–intestinal microvessels of normal mice with that in transgenic knockout sickle cell mice that have erythrocytes containing only human hemoglobin S and that exhibit a degree of hemolytic anemia and pathological complications similar to the human disease. In sickle cell mice, in addition to seeing blood flow abnormalities such as sludging in all microvessels, we detected decreased blood flow velocity in venules of all diameters. Flow responses to hyperoxia in both normal and sickle cell mice were dramatic, but opposite: Hyperoxia promptly slowed or halted flow in normal mice but markedly enhanced flow in sickle cell mice. Intravital microscopic studies of this murine model provide important insights into sickle cell blood flow abnormalities and suggest that this model can be used to evaluate the causes of abnormal flow and new approaches to therapy of sickle cell disease.
GPR120 on Kupffer cells mediates hepatoprotective effects of ω3-fatty acids
Authors: Dimitri Aristotle Raptis, Perparim Limani, Jae Hwi Jang, Udo Ungethüm, Christoph Tschuor, Rolf Graf, Bostjan Humar, Pierre-Alain Clavien
Journal: Journal of Hepatology (2013)
Laboratory Evaluation of Hemostasis and Thrombosis
Authors: David Green
Journal: JAMA (1984)

The third edition of this text has been reorganized and expanded to include a great deal of new material of importance to the clinical laboratory, in keeping with the authors' avowed goal of emphasizing those studies that can be performed accurately—and that are useful in the diagnosis of disease states and the care of patients. For example, the section on the activated partial thromboplastin time (APTT) has been considerably enlarged by a thorough discussion of the principles of the method, its pitfalls, and the way this test can be modified to differentiate clotting factor deficiencies, examine contact activation, and be used for heparin control. New sections have been added on the evaluation of platelet-function defects, clotting-factor deficiencies, fibrinolysis, and thrombosis. New assays included are fluorogenic substrate methods for plasminogen and heparin, radioimmunoassays for β-thromboglobulin and platelet factor 4, tests for circulating platelet aggregates, and a variety of methods for measuring
Atopic dermatitis 2.0: from the clinical phenotype to the molecular taxonomy and stratified medicine
Authors: Th. Bieber
Journal: Allergy (2012)

Abstract Atopic dermatitis ( AD ) is a paradigmatic inflammatory chronic skin disease. As for other chronic skin diseases, (i) the spectrum of the clinical phenotype and severity as well as (ii) the genetic background and (iii) the underlying mechanisms strongly suggest a high degree of pathophysiological heterogeneity yet leading to a similar clinical pattern, that is, the eczematous skin lesion, but showing distinct progression patterns. This review suggests to exploit the recent knowledge about AD for a novel approach proposing a tentative first molecular taxonomy of this disease based on the genotype and endophenotype. The consequences in terms of personalized prevention and management are delineated.
Prospective Study of Hyperhomocysteinemia as an Adverse Cardiovascular Risk Factor in End-Stage Renal Disease
Authors: Ali Moustapha, Arabi Naso, Maher Nahlawi, Anjan Gupta, Kristopher L. Arheart, Donald W. Jacobsen, Killian Robinson, Vincent W. Dennis
Journal: Circulation (1998)

Retrospective and case-control studies show that hyperhomocysteinemia is an independent risk factor for atherosclerosis in patients with end-stage renal disease. We studied prospectively the association between total homocysteine and cardiovascular outcomes.In all, 167 patients (93 men, 74 women; mean age, 56.3+/-14.7 years) were followed for a mean duration of 17.4+/-6.4 months. Cardiovascular events and causes of mortality were related to total homocysteine values and other cardiovascular risk factors. Cox regression analysis was used to identify the independent predictors for cardiovascular events and mortality. Fifty-five patients (33%) developed cardiovascular events and 31 (19%) died, 12 (8%) of cardiovascular causes. Total plasma homocysteine values ranged between 7.9 and 315.0 micromol/L. Levels were higher in patients who had cardiovascular events or died of cardiovascular causes (43.0+/-48.6 versus 26.9+/-14.9 micromol/L, P=.02). The relative risk (RR) for cardiovascular events, including death, increased 1% per micromol/L increase in total homocysteine concentration (RR, 1.01; CI, 1.00 to 1.01; P=.01).These prospective observations confirm that hyperhomocysteinemia is an independent risk factor for cardiovascular morbidity and mortality in end-stage renal disease, with an increased RR of 1% per micromol/L increase in total homocysteine concentration. Interventional studies are needed to evaluate the possible effects of modifying this risk factor in these patients.
Hemodynamic Patterns for Symptomatic Presentations of Severe Aortic Stenosis
Authors: Sung-Ji Park, Maurice Enriquez-Sarano, Sung-A. Chang, Jin-Oh Choi, Sang-Chol Lee, Seung Woo Park, Duk-Kyung Kim, Eun-Seok Jeon, Jae K. Oh
Journal: JACC. Cardiovascular imaging (2013)
Complications of Urologic Surgery: Prevention and Management
Authors: Frank Hinman
Journal: JAMA (1991)

This second edition of a valuable book first published in 1976 is more comprehensive and brings the subject up to 1988 (a two-year time lag is usual with multiauthored books). Complications are a recurrent problem for urologists, especially with the newer procedures such as bladder augmentation and percutaneous stone extraction. Smith and Ehrlich have assembled the stars of urologic surgery—including themselves— to write from personal experience, making the book highly authoritative. All of the major and many of the minor complications are included so that the urologist not only may anticipate and avoid them, but also may use the recommendations of the authors to correct them should they occur. The complications are clearly described and their remedies can be readily applied. The first several chapters on metabolic, pulmonary, infectious, cardiac, and anesthetic principles and complications are scholarly and instructive and will be a fine source for study, although more focus
RHEUMATOID ARTHRITIS: A PERSONAL EXPERIENCE OF THE DISEASE
Authors: F. H. Parker
Journal: BMJ (1911)

RHEUMATOID ARTHRITIS.IM DwItJosrr 135T feebler and slower, and everywllere there are indications of the diminished ability to metabolize the anmount of proteini according to Voit's standard; and iii old age the amount consumed ought to approach somewhat nearer to the physiological minimum.Many persons in old age actually do reduce the amotint cansuime-d to the physiological requirements.I could give instances of old people wiho actually consume nlo mQre than 30 granis of protein daily, and, nevertheless, -enjoy moderate health, or do not suffer from any appreciable disease.But as regards children, growing.persons, and young adults, the general principles la;id'down should guide us; and when the cost of animal food is prohibitive a freer use of vegetable proteins-legumes and nuts-should be recoimmended.
987-105 Transesophageal Echocardiographic Quantltation of Systolic Mitral Leaflet Displacement In Patients with Mitral Valve Prolapse
Authors: David Langholz, William J. Mackin, Diane E. Wallis, William R. Jacobs, Patrick J. Scanlon, Eric K. Louie
Journal: Journal of the American College of Cardiology (1995)
Reduced Red Cell Filterability with Oral Contraceptive Agents
Authors: FRANK A. OSKI
Journal: Annals of Internal Medicine (1972)

Women taking oral contraceptives had red cells with decreased filterability. The mean half-life for red cell filtration was 6.23 minutes in 34 such women, as contrasted with 4.16 minutes in 36 control women. Within 2 to 3 days of discontinuing therapy the filterability improved significantly. Similar changes in red cell filtration were produced in four male volunteers. These changes occured within 1 to 3 days of the initiation of therapy with a combination of norethindrone and mestranol. It is proposed that the red cell rigidity produced by the ingestion of oral contraceptives may produce stasis in the microcirculation, which might ultimately lead to thrombosis.
Endocardial Fibrosis Following Busulfan Treatment
Authors: Abraham Weinberger
Journal: JAMA (1975)

PROLONGED treatment with busulfan (1,4 dimethanesulfonyloxybutane), the drug of choice in chronic myeloid leukemia (CML), is known to cause interstitial pulmonary fibrosis.<sup>1</sup>The autopsy of a patient with CML treated for nine years with busulfan demonstrated, in addition to this complication, endocardial fibrosis of the left ventricle, a side effect, to our knowledge, hitherto undescribed. <h3>Report of a Case</h3> In 1960, a 67-year-old woman underwent total hysterectomy for adenocarcinoma of the uterus. At that time, the peripheral blood cell count was normal. In 1963, when she complained of severe weakness, a white blood cell (WBC) count of 45,000/cu mm with a large number of promyelocytes and metamyelocytes, as well as a neutrophil alkaline phosphatase score of zero, were found. A bone marrow aspiration biopsy disclosed marked proliferation of the myeloid cell series. The diagnosis of CML was made and treatment with pusulfan, 4 mg daily, was started. The patient
Lament of an Unsuccessful Weight Watcher
Authors: Marian J. Lewis
Journal: JAMA (1972)

<h3>To the Editor.—</h3> My intertriginosity Is caused by adiposity; I wonder where the increment will end? Such fleshly generosity Impedes my true velocity And also makes it difficult to bend. I have no curiosity To be a great monstrosity— Such wishfulness I cannot comprehend; In fact, this corporosity Fills me with animosity, Because I can't reverse the "growing" trend!
Crime and the Aged
Authors: Manuel Rodstein
Journal: JAMA (1975)

AGED perpetrators of crime are not of major importance in the totality of criminality and constitute only a small proportion of the total aged population. However, there are many interesting and largely unexplored aspects of criminality among the aged. These include the differences in the types of crime and the nature of punishment of crime between the aged and younger individuals, the life history of the young criminal advancing into old age, the etiology of crime appearing for the first time late in life, and the effects of social class and cultural background on the nature of crime committed by the aged. <h3>Incidence</h3> Only 5% of prisoners are more than 45 years of age. This may represent the reluctance of judges and juries to send older people to jail because of health and family reasons and the fact that old people do not usually commit the more violent types of
Suppression of chemotactic activity of human polymorphonuclears by monoclonal IgMs with and without biological activity
Authors: W. Pruzanski, D. W. Nitzan, S. Saito
Journal: American Journal of Hematology (1986)

Abstract The influence of monoclonal IgMs on migration of human polymorphonuclears was studied at various temperatures by the use of 19 sera with monoclonal IgMs from patients with macroglobulinemia of Waldenstrom (MW) without obvious biological activity, 29 sera with monoclonal IgM cold agglutinins (18 with anti‐I and 11 with anti‐i IgMs) and 3 sera with monoclonal IgM rheumatoid factor (RF). Under‐agarose migration method and modified Boyden chamber method with double filters and 51 Cr‐PMNs were used. In under‐agarose method, chemotactic differentials for controls, MW, anti‐I, and anti‐i groups were, respectively, 57 ± 8 mm, 39 ± 9 mm, 44 ± 14 mm, and 32 ± 16 mm at 37°C and 47 ± 18 mm, 22 ± 11 mm, 17 ± 9 mm, and 15 ± 12 mm at 24°C. All three sera with IgM RF inhibited chemotaxis. The differences between all groups and controls were significant at p &lt; 0.01. Random migration was inhibited at 24°C (p &lt; 0.01) but not at 37°C. Inhibitory concentrations of IgM in the sera tested were equal or less than 0.5 mg/ml. Thirteen sera were tested by the modified Boyden chamber method. At 37°C 8 of 13 sera and at 24°C 11 of 13 sera inhibited significantly chemotaxis at a concentration of IgM of 1 mg/ml. The lowest inhibitory concentration of IgM was 25 μg/ml. Eleven chromatographically pure IgMs were tested in the under‐agarose assay. At concentrations of 0.4‐3.7 mg/ml, eight IgMs inhibited chemotactic differential at 37°C and nine inhibited it at 24°C. At concentrations of 0.6‐2.0 mg/ml, all seven pure IgMs tested by the Boyden chamber method significantly inhibited chemotaxis at 24°C and 37°C. Some IgMs inhibited chemotaxis at concentrations as low as 25 μ/ml. Ten IgM CA were eluted from the red blood cells. Eluates inhibited strongly chemotaxis at 24°C and 37°C. Heat inactivation did not alter inhibitory activity of IgM, however pepsin digestion or reduction and alkylation of purified IgMs did abolish their inhibitory activity. Inhibition of chemotaxis was not related to the light chain type, the titre, or the thermoamplitude of cold agglutination. However, monoclonal IgMs with anti‐i cold agglutinin activity were stronger inhibitors than anti‐I. Since 75% of IgMs tested inhibited chemotaxis at 37°C, it is possible that monoclonal IgMs, especially those with anti‐i cold agglutinin activity, inhibit PMN migration in vivo.
Hypertonic saline increases secretory and exudative responsiveness of human nasal airway<i>in vivo</i>
Authors: L. Greiff, M. Andersson, P. Wollmer, C.G.A. Persson
Journal: European Respiratory Journal (2003)

Hypertonic saline (HS) is used in sputum induction studies. However, little is known about the physiological effects of HS on human airways in vivo . The present study takes advantage of the fact that the airway effects of topical challenges may be accurately examined in the readily accessible nasal airway. The present study specifically examines whether exposure to HS affects histamine challenge-induced exudation of plasma (α 2 -macroglobulin) and methacholine-induced secretion of mucin (fucose). Isotonic saline and HS (27 and 45 g·L −1 ), with and without concomitant histamine challenges, and with and without preceding methacholine challenges, were administered onto the nasal mucosa in 16 healthy subjects. Lavage fluid levels of α 2 -macroglobulin and fucose were analysed. Histamine produced a significant mucosal output of plasma (α 2 -macroglobulin). HS itself did not evoke exudation of α 2 -macroglobulin, but it significantly increased the plasma exudation effect of histamine. Methacholine produced a significant nasal mucosal output of fucose. HS also increased the mucin secretion (fucose), and it enhanced the secretory effect of methacholine. The authors concluded that hypertonic saline alone evokes mucinous secretion in human nasal airways in vivo and that it also enhances the exudative and secretory effects of histamine and methacholine, respectively. Through different mechanisms the HS exposure may also improve the recovery of soluble indices in human nasal airways. Whether or not the present findings are translatable to human bronchial airways remains to be examined.
Development of a Type 2 Diabetes Risk Model From a Panel of Serum Biomarkers From the Inter99 Cohort
Authors: Robert W. Gerwien, Michael W. Rowe, Edward Moler, Mickey S. Urdea, Michael P. McKenna, Janice A. Kolberg
Journal: Diabetes Care (2010)

Rathmann, Kowall, and Schulze (1) suggest that the diabetes risk score (DRS) model is no better than simple clinical models and thus is of limited utility. To support this contention, they compare our area under the receiver operating characteristic curve (AROC) with those reported for different models. However, the AROC of a test is population specific; therefore, comparisons between populations with different baseline risks are problematic because sensitivity and specificity are subject to alteration by disease prevalence (2). In general, the AROC decreases as prevalence increases as it is increasingly difficult to differentiate outcomes in less healthy populations. The Inter99 subpopulation with age >39 years and BMI ≥25 kg/m2 that we used had a 5-year risk of 5.7%, nearly 2.5-fold higher …
Cetuximab Monotherapy in Patients with Advanced Non-small Cell Lung Cancer After Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy
Authors: Joel W. Neal, Rebecca S. Heist, Panos Fidias, Jennifer S. Temel, Mark Huberman, J. Paul Marcoux, Alona Muzikansky, Thomas J. Lynch, Lecia V. Sequist
Journal: Journal of Thoracic Oncology (2010)
Controversy sparked in Switzerland after doctor who used unproved, unlicensed therapy is cleared of non-treatment conviction
Authors: N. Stafford
Journal: BMJ (2009)

A decision by Switzerland’s highest court to overturn a doctor’s conviction for failing to treat effectively “several patients” with cancer has been described as “a judicial scandal with disastrous ethical and medical implications” by a patients’ rights group.

However, the Swiss Medical Association’s top lawyer disagrees, saying that strict new laws will prevent similar cases in the future.

According to a judgment, issued 20 June 2008 by the Swiss Federal Court, an oncologist practising in Basel, referred to as X, treated at least 186 patients for breast or other cancers in 1998 and 1999 with lipoteichoic acid (LTA), which was manufactured by his company, although it was not licensed for such treatment. The standard treatment for some of the patients was tamoxifen, but in some cases this was stopped by Dr X in favour of lipoteichoic acid.

One of the patients, known as Mrs Ad, was central to the case. According to the judgment she developed breast cancer in 1997, and after surgery on 14 August, was started on tamoxifen. Dr X started seeing her on 26 August that year and stopped tamoxifen in December 1997 even though evidence showed that treatment with the drug for five years substantially reduces the risk of recurrence.

“Instead of using the standard treatment indicated, …
Too much claret
Authors: Theodore Dalrymple
Journal: BMJ (2008)

As is well known, Samuel Taylor Coleridge was an opium addict. He took opium in the form of laudanum, that is to say tincture of opium in alcohol, which he drank by the pint. In addition, he was no mean bibber of claret; not a 21-unit-a-week man (or whatever the latest safe level of consumption is), but more like an all-you-can-drink man.

Several witnesses testified to his morning shakes and sweats, which improved after his first laudanum of the day, and in general this has been taken as evidence of his addiction to opium. However, it seems to me more likely that he was suffering from the withdrawal effects of alcohol. The trouble for literary types is that alcohol …
In defence of the community health council
Authors: A. Youngs
Journal: BMJ (1980)

Hereditary haemochromatosis (HH) is a genetic disorder in which abnormal iron handling leads to excessive iron accumulation in systemic tissues. Magnetic resonance imaging studies suggest excess iron deposition in the basal ganglia of patients with HH. The symptoms of neurological complications of HH include cognitive decline, gait difficulties, cerebellar ataxia, and extrapyramidal dysfunction, but idiopathic Parkinson’s disease, in which brain iron deposition is normal, has not been reported. We describe four patients with concurrent HH and IPD. Although three of the cases had risk factors for cerebrovascular and cardiovascular disease, computed tomography did not show ischaemic changes in the basal ganglia. We speculate that in these cases, abnormal deposition of iron in the basal ganglia induced the symptoms of IPD.
Apoptotic Signaling Pathways Induced by Nitric Oxide in Human Lymphoblastoid Cells Expressing Wild-Type or Mutant p53
Authors: Chun-Qi Li, Ana I. Robles, Christin L. Hanigan, Lorne J. Hofseth, Laura J. Trudel, Curtis C. Harris, Gerald N. Wogan
Journal: Cancer Research (2004)

Abstract Loss of p53 function by inactivating mutations results in abrogation of NO·-induced apoptosis in human lymphoblastoid cells. Here we report characterization of apoptotic signaling pathways activated by NO· in these cells by cDNA microarray expression and immunoblotting. A p53-mediated transcriptional response to NO· was observed in p53-wild-type TK6, but not in closely related p53-mutant WTK1, cells. Several previously characterized p53 target genes were up-regulated transcriptionally in TK6 cells, including phosphatase PPM1D (WIP1), oxidoreductase homolog PIG3, death receptor TNFRSF6 (Fas/CD95), and BH3-only proteins BBC3 (PUMA) and PMAIP1 (NOXA). NO· also modulated levels of several gene products in the mitochondria-dependent and death-receptor-mediated apoptotic pathways. Inhibitors of apoptosis proteins X-chromosome-linked inhibitor of apoptosis, cellular inhibitor of apoptosis protein-1, and survivin were significantly down-regulated in TK6 cells, but not in WTK1 cells. Smac release from mitochondria was induced in both cell types, but release of apoptosis-inducing factor and endonuclease G was detected only in TK6 cells. Fas/CD95 was increased, and levels of the antiapoptotic proteins Bcl-2 and Bcl-x/L were reduced in TK6 cells. Activation of procaspases 3, 8, 9, and 10, as well as Bid and poly(ADP-ribose) polymerase cleavage, were observed only in TK6 cells. NO· treatment did not alter levels of death receptors 4 and 5, Fas-associated death domain or proapoptotic Bax and Bak proteins in either cell line. Collectively, these data show that NO· exposure activated a complex network of responses leading to p53-dependent apoptosis via both mitochondrial and Fas receptor pathways, which were abrogated in the presence of mutant p53.