tbuckley/cabot-search huggingface dataset:
Striking the target in iron overload disorders
Authors: Karin E. Finberg
Journal: Journal of Clinical Investigation (2013)

The liver, a major site of body iron stores, mediates key responses that preserve systemic iron homeostasis. In this issue of the JCI, Guo et al. demonstrate that administration of antisense oligonucleotides that reduce expression of Tmprss6, a hepatic protein that plays an essential role in maintaining iron balance, can attenuate disease severity in mouse models of human iron overload disorders. These data reveal the potential of novel TMPRSS6-targeted therapies for the treatment of clinical conditions such as hereditary hemochromatosis and β-thalassemia.
Endoscopic approach in the treatment of carcinoid tumors
Authors: Levent Dalar, Ahmet Levent Karasulu, Seda Onur, Sinem Nedime Sokucu, Aysegul Akbas, Sedat Altin
Journal: European Respiratory Journal (2012)

Aim: Carcinoid tumors were the neuroendocrine tumors of the tracheobronchial tree. Treatment approaches with interventional bronchoscopic methods in carcinoid tumors have been analyzed and discussed.

Method: In this study, 20 consecutive carcinoid tumor patient treated in between January 2006 to August 2011 in our Interventional Pulmonology Unit were evaluated. All patients undergone rigid bronchoscopy. In all of the patients after coagulation with diode laser or APC tumor tissue was totaly removed with core-out method. Tumors diagnosed as TC after pathological evaluation cryotherapy and/or laser was applied as a complementary procedure. Long follow up and treatment efficacy, recurrence and residive ratios, complications, mortality and morbidity were evaluated.

Results: From the 20 cases included into the study, 17 of them were TC and 3 of them were AC. Mean age of the cases were 56 (between 20-73) and 14 of them were female. Six cases, two of them were AC, were operated after bronchoscopic treatment. Rigid bronchsocopy was applied as a mean of 2.3 (1-5) times while fiberoptic bronchsocpy was applied as a mean of 3.2 times. Radial probe EBUS and otofluorescent broncoscopy were used in bronchoscopic follow up. No mortality due to bronchoscopic treatment was observed.

Conclusion: Bronchoscopic treatment is effective and safe in endobronchial carcinoid cases in which tumor base could be totally visualized bronchoscopically and pathological evaluation revealed diagnosis of TC. Efficacy could be reached by the meticulous application of the standard bronchoscopic procedure. Close follow up and treatment of recurrences is essential in the early period.
Safety and Efficacy of Nanofiltered C1 Esterase Inhibitor (Human) (Cinryze™) for the Treatment of Laryngeal Attacks in Subjects with Hereditary Angioedema (HAE)
Authors: M. Riedl, J. Baker, D. Hurewitz, W.R. Lumry, A. Vegh, M. White, J.A. Grant, P. Busse, A. Rubinstein, I. Kalfus
Journal: Journal of Allergy and Clinical Immunology (2011)
External metabolic balance studies during nasogastric feeding in serious illnesses requiring intensive care.
Authors: M. J. Peaston
Journal: BMJ (1966)

The importance of nasogastric feeding in serious illness was first appreciated by John Hunter in 1776, and in 1790 he achieved complete nasogastric alimentation for 18 days in a man with paralytic dysphagia (Hunter, 1837). A tube feed of milk powder (Complan) and lactose was recently described which maintained metabolic balance in patients with a variety of serious illnesses in an intensive-care unit (Jones and Sechiari, 1963). In patients with respiratory failure requiring inter mittent positive-pressure ventilation (I.P.P.V.) that diet was complicated by an incidence of diarrhoea approaching 20% (Jones and Peaston, 1966). This paper describes a modified tube feed in which external metabolic balance data confirmed
Assignment of Tangier disease to chromosome 9q31 by a graphical linkage exclusion strategy
Authors: Stephan Rust, Michael Walter, Harald Funke, Arnold von Eckardstein, Paul Cullen, Hester Y. Kroes, Roel Hordijk, Jürgen Geisel, John Kastelein, Henri O.F. Molhuizen, Michaela Schreiner, Anja Mischke, Harry W. Hahmann, Gerd Assmann
Journal: Nature Genetics (1998)
<i>The Emotions, Morality and the Brain.</i>By C. von Monakow. Authorized translation by Gertrude Barnes, A. M., and Smith Ely Jelliffe, M. D., Ph. D. Nervous and Mental Disease Monograph Series No. 39. (<i>Washington and New York: Nervous and Mental Disease Publishing Co., 1925.</i>)
Authors: C. O. Fiertz
Journal: American Journal of Psychiatry (1927)
Re: Continuing Outcomes Relevant to Evista: Breast Cancer Incidence in Postmenopausal Osteoporotic Women in a Randomized Trial of Raloxifene
Authors: B. Yalcin, A. Buyukcelik, S. Yalcin, G. Utkan, H. Doruk, M. Dogan, M. Altan
Journal: JNCI Journal of the National Cancer Institute (2005)
Neurocognitive Function and Progression in Patients With Brain Metastases Treated With Whole-Brain Radiation and Motexafin Gadolinium: Results of a Randomized Phase III Trial
Authors: Christina A. Meyers, Jennifer A. Smith, Andrea Bezjak, Minesh P. Mehta, James Liebmann, Tim Illidge, Ian Kunkler, Jean-Michel Caudrelier, Peter D. Eisenberg, Jacobus Meerwaldt, Ross Siemers, Christian Carrie, Laurie E. Gaspar, Walter Curran, See-Chun Phan, Richard A. Miller, Markus F. Renschler
Journal: Journal of Clinical Oncology (2003)

To report the neurocognitive findings in a phase III randomized trial evaluating survival and neurologic and neurocognitive function in patients with brain metastases from solid tumors receiving whole-brain radiation therapy (WBRT) with or without motexafin gadolinium (MGd).Patients were randomly assigned to receive WBRT 30 Gy in 10 fractions with or without MGd 5 mg/kg/d. Monthly neurocognitive testing for memory, executive function, and fine motor skill was performed.Four hundred one patients were enrolled (251 with non-small-cell lung cancer, 75 with breast cancer, and 75 with other cancers); 90.5% patients had impairment of one or more neurocognitive tests at baseline. Neurocognitive test scores of memory, fine motor speed, executive function, and global neurocognitive impairment at baseline were correlated with brain tumor volume and predictive of survival. There was no statistically significant difference between treatment arms in time to neurocognitive progression. Patients with lung cancer (but not other types of cancer) who were treated with MGd tended to have improved memory and executive function (P =.062) and improved neurologic function as assessed by a blinded events review committee (P =.048).Neurocognitive tests are a relatively sensitive measure of brain functioning; a combination of tumor prognostic variables and brain function assessments seems to predict survival better than tumor variables alone. Although the addition of MGd to WBRT did not produce a significant overall improvement between treatment arms, MGd may improve memory and executive function and prolong time to neurocognitive and neurologic progression in patients with brain metastases from lung cancer.
Call for shake up in NHS funding: Clarifications from Doctors for Reform
Authors: C David H Wrede
Journal: BMJ (2006)

EDITOR—I wish to respond to some of the misrepresentation that has followed your news article about Doctors for Reform.1

Firstly, the steering committee consists of NHS doctors committed to equity of provision and access to health services according to clinical need, which should be free at the point of use. I have worked for 23 years in the NHS and have never seen private patients under my …
Wegener's granulomatosis autoantibodies identify a novel diisopropylfluorophosphate-binding protein in the lysosomes of normal human neutrophils.
Authors: R Goldschmeding, C E van der Schoot, D ten Bokkel Huinink, C E Hack, M E van den Ende, C G Kallenberg, A E von dem Borne
Journal: Journal of Clinical Investigation (1989)

Anti-neutrophil cytoplasmic autoantibodies (ANCA) specifically associated with Wegener's granulomatosis were found to be directed against a saline-soluble glycoprotein triplet that migrates on SDS gels as distinct bands of Mr 29,000, 30,500, and 32,000 and is present in the azurophilic granules. This antigen was specifically recognized by all cytoplasmic-staining (C)-ANCA-positive sera from patients with Wegener's disease. C-ANCA antigen bound [3H]diisopropylfluorophosphate, which indicates that it is a serine protease, but it could clearly be distinguished from the serine proteases elastase and cathepsin G. Stimulation of cytochalasin B-treated neutrophils with FMLP induced release of C-ANCA antigen. This indicates that in vivo C-ANCA might interact with the C-ANCA antigen after its release upon inflammatory stimulation. We further demonstrate that in some perinuclear staining (P-ANCA) patients' sera autoantibodies against other myeloid lysosomal enzymes can be detected, such as antimyeloperoxidase and antielastase. C-ANCA and P-ANCA thus represent a novel class of autoantibodies directed against myeloid lysosomal enzymes. The originally described Wegener-specific C-ANCA show an apparently uniform specificity for the 29,000 serine protease. In contrast, P-ANCA may recognize myeloperoxidase as well as elastase and/or other antigens.
Transluminal endoscopic necrosectomy for pancreatic necrosis: in all hands and for all patients, or with selected endoscopists in selected patients?
Authors: M. Barthet, S. Ezzedine
Journal: Gut (2009)

In this issue of Gut , Seifert et al 1 (see page 1260) , in a multicentre study from Germany, have investigated the results of endoscopic treatment of pancreatic necrosis. The paper highlights the long-term results of this endoscopic management, considered from an endoscopic point of view as an aggressive treatment but from a surgical point of view as a minimally invasive treatment. The endoscopic management of pancreatic necrosis is moving to the frontier between surgery and endoscopy. Transluminal endoscopic necrosectomy is probably the first step of NOTES (natural orifice trans-endoscopic surgery) procedures in humans.

The first limitation of transluminal endoscopic necrosectomy after acute pancreatitis (TENAP) series is the definition of pancreatic necrosis. Transmural endoscopic drainage of pancreatic pseudocysts or abscesses has been performed since the 1980s and is becoming a standardised procedure.2 Recently, endoscopic ultrasound (EUS) guidance of such complications of acute pancreatitis has expanded the field of the endoscopic treatment of pancreatic pseudocysts and made it safer. More than half of the pseudocysts do not bulge through the digestive wall and are not amenable to conventional endoscopic drainage.2 In addition, portal hypertension due to thrombosis or compression of the splenic vein by the pseudocysts increases the risk of bleeding. It has been demonstrated that EUS guidance is required in about half of the patients to achieve drainage of pancreatic pseudocysts or abscesses.2 However, according to the Atlanta classification, pseudocysts or abscesses are fluid collections originating from the pancreas, not only due to acute pancreatitis but also to ductal obstruction in cases of chronic pancreatitis. These lesions are fluid collections without necrotic debris or a solid component, which can be drained by stenting through the digestive wall, with or without associated nasocatheter drainage for a few days at the beginning of the drainage. Pancreatic necrosis …
Family history of end-stage renal disease among incident dialysis patients.
Authors: B I Freedman, J M Soucie, W M McClellan
Journal: Journal of the American Society of Nephrology (1997)

As part of a larger study of genetic risk factors for the occurrence of renal failure, the prevalence of a family history of end-stage renal disease (ESRD) in first- and second-degree relatives of all incident dialysis patients treated in Georgia, North Carolina, and South Carolina (ESRD Network 6) in 1994 was ascertained. Family histories were obtained from 4365 dialysis patients (83% of those eligible), and 856 (20%) reported having a family history of ESRD. Among race-sex groups, 14.1% of Caucasian men, 14.6% of Caucasian women, 22.9% of African-American men, and 23.9% of African-American women reported a first- or second-degree relative with ESRD (P = 0.001). The prevalence of relatives with ESRD varied by the reported etiology: 22.2% in diabetes mellitus; 18.9% in hypertension, 22.7% in glomerulonephritis; and 13.0% of other etiologies (P = 0.001). Patient characteristics independently associated with family history of ESRD included race, younger age, higher levels of education, and etiology of ESRD. In this report, it is concluded that a large proportion of incident ESRD cases have close relatives with ESRD in whom preventive actions might be directed. Genetic analyses in multiply affected families may identify the inherited factors contributing to progressive renal failure.
A Key Role for Cc Chemokine Receptor 4 in Lipopolysaccharide-Induced Endotoxic Shock
Authors: Yolande Chvatchko, Arlene J. Hoogewerf, Alexandra Meyer, Sami Alouani, Pierre Juillard, Raphaele Buser, Francois Conquet, Amanda E.I. Proudfoot, Timothy N.C. Wells, Christine A. Power
Journal: The Journal of Experimental Medicine (2000)

CC chemokine receptor (CCR)4, a high affinity receptor for the CC chemokines thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC), is expressed in the thymus and spleen, and also by peripheral blood T cells, macrophages, platelets, and basophils. Recent studies have shown that CCR4 is the major chemokine receptor expressed by T helper type 2 (Th2) polarized cells. To study the in vivo role of CCR4, we have generated CCR4-deficient (CCR4(-/-)) mice by gene targeting. CCR4(-/-) mice developed normally. Splenocytes and thymocytes isolated from the CCR4(-/-) mice failed to respond to the CCR4 ligands TARC and MDC, as expected, but also surprisingly did not undergo chemotaxis in vitro in response to macrophage inflammatory protein (MIP)-1alpha. The CCR4 deletion had no effect on Th2 differentiation in vitro or in a Th2-dependent model of allergic airway inflammation. However, CCR4(-/-) mice exhibited significantly decreased mortality on administration of high or low dose bacterial lipopolysaccharide (LPS) compared with CCR4(+/+) mice. After high dose LPS treatment, serum levels of tumor necrosis factor alpha, interleukin 1beta, and MIP-1alpha were reduced in CCR4(-/-) mice, and decreased expression of MDC and MIP-2 mRNA was detected in peritoneal exudate cells. Analysis of peritoneal lavage cells from CCR4(-/)- mice by flow cytometry also revealed a significant decrease in the F4/80(+) cell population. This may reflect a defect in the ability of the CCR4(-/-) macrophages to be retained in the peritoneal cavity. Taken together, our data reveal an unexpected role for CCR4 in the inflammatory response leading to LPS-induced lethality.
Receiving the Diagnosis of Lung Cancer: Patient Recall of Information and Satisfaction With Physician Communication
Authors: Sabine Gabrijel, Leticia Grize, Erich Helfenstein, Martin Brutsche, Paul Grossman, Michael Tamm, Alexander Kiss
Journal: Journal of Clinical Oncology (2008)

Little is known about the information newly diagnosed patients with lung cancer recall and how satisfied they are with physicians' communication.Seventy-one consecutive patients with newly diagnosed lung cancer were surveyed 1 to 3 days after the disclosure of diagnosis. Patients' recall of the given information was assessed, as well as their satisfaction with physicians' communication of diagnosis, treatment procedure, and goal of treatment as curative or palliative. Physicians who provided diagnosis were asked to complete a questionnaire concerning what information they had given to the patient. Congruence between physician information and patient recall of that information was then evaluated.Ninety percent (62 of 69 patients) correctly recalled their physician's information about the diagnosis, 83% (55 of 66 patients) knew what treatment procedure their physicians proposed, and 49% (32 of 65 patients) accurately recalled information about the goal of treatment. Seventy-six and 73% of patients were highly satisfied with their physician's communication of diagnosis and treatment procedure, respectively. Only 39% were highly satisfied with communication of the treatment goal. Patients who correctly recalled information regarding the treatment procedure were significantly more satisfied with its communication.Recall of information about the intent of treatment is poor, and satisfaction with communication of the intent of treatment is lacking among newly diagnosed patients with lung cancer. Future studies should address whether specific interventions can improve these deficiencies.
Relocalized p27Kip1 Tumor Suppressor Functions as a Cytoplasmic Metastatic Oncogene in Melanoma
Authors: Catherine Denicourt, Cheryl C. Saenz, Brian Datnow, Xian-Shu Cui, Steven F. Dowdy
Journal: Cancer Research (2007)

Abstract The p27 tumor suppressor negatively regulates G1 cell cycle progression. However, human malignancies rarely select for deletion/inactivation of p27, a hallmark of tumor suppressor genes. Instead, p27 is degraded or relocalized to the cytoplasm in aggressive malignancies, supporting the notion that p27 sequestration from its nuclear cyclin:cyclin-dependent kinase (cdk) targets is critical. However, emerging cell biology data suggest a novel cdk-independent cytoplasmic function of p27 in cell migration. Here, we find cytoplasmic p27 in 70% of invasive and metastatic melanomas. In contrast, no cytoplasmic p27 was detected in noninvasive, basement membrane–confined melanoma in situ, suggesting a late oncogenic role for cytoplasmic p27 in metastasis. Targeted cytoplasmic expression of wild-type or non–cdk-binding p27 at subphysiologic levels induced melanoma motility and resulted in numerous metastases to lymph node, lung, and peritoneum. These observations point to a prominent role of cytoplasmic p27 in metastatic disease that is independent of cyclin:cdk regulation or mere nuclear loss. [Cancer Res 2007;67(19):9238–43]
Deficiency of the 5-Hydroxytryptamine Transporter Gene Leads to Cardiac Fibrosis and Valvulopathy in Mice
Authors: A. Mekontso-Dessap, F. Brouri, O. Pascal, P. Lechat, N. Hanoun, L. Lanfumey, I. Seif, N. Benhaiem-Sigaux, M. Kirsch, M. Hamon, S. Adnot, S. Eddahibi
Journal: Circulation (2005)

Background— Serotonin (5-hydroxytryptamine; 5-HT) overproduction is responsible for cardiac valvular disease in patients with carcinoid tumors. Reduced 5-HT inactivation is one proposed mechanism of the valvulopathy observed in individuals treated with the appetite suppressants fenfluramine and phentermine. One key protein limiting systemic availability of 5-HT is the 5-HT transporter (5-HTT) expressed by platelets and pulmonary vascular cells; 5-HTT is responsible for 5-HT uptake and subsequent inactivation of the amine passing through the lung. Here we investigated whether 5-HTT–deficient (5-HTT-KO) mice developed structural and/or functional cardiac abnormalities and valvulopathy. Methods and Results— Cardiac endothelial cells expressed large amounts of 5-HTT in wild-type mice. 5-HTT deficiency appeared to be associated with marked interstitial, perivascular, and valvular fibrosis as evidenced by staining of cardiac collagen in 5-HTT-KO mice. Histological analysis provided evidence for valvulopathy characterized by valvular hyperplasia and prominent fibrosis at the attachment site and base of the leaflets. Echocardiography revealed an increase in left ventricular lumen diameter and a decrease in left ventricular diameter fractional shortening. Although 5-HT 1B receptors mediated the 5-HT–induced collagen secretion by human cardiac myofibroblasts, the contribution of this receptor type to valvulopathy was ruled out because double-KO mice deficient in both 5-HTT and 5-HT 1B receptors showed the same cardiac alterations as 5-HTT-KO mice. Conclusions— The present results establish a link between 5-HTT and the development of cardiac fibrosis and valvulopathy in vivo. 5-HTT-KO mice represent an especially relevant model for studying the mechanisms by which 5-HT induces valvulopathy.
Spontaneous antithrombin in a patient with benign paraprotein
Authors: Don A. Gabriel, Marcus E. Carr, Linda Cook, Harold R. Roberts
Journal: American Journal of Hematology (1987)

Abstract A 66‐year‐old man with peptic ulcer desease developed a paraprotein that resulted in a spontaneously prolonged prothromoin time, activated partial thromboplastin time, and thrombin clotting time. Although the reptilase time was normal, the thrombin clotting time failed to correct with the addition of normal plasma, calcium, or protamine sulfate. The patient's purified fibrinogen was normal, but his serum contained an IgG that inhibited the clotting of normal plasma and purified fibrinogen in the presence of thrombin. In contrast to previously described paraproteins, this patient's IgG appeared to inhibit the activity of thrombin per se rather than to interfere with fibrinogen cleavage or fibrin polymerization. Although immunoprecipitation between thrombin and the paraprotein could not be demonstrated, the patient's purified IgG, in the presence of thrombin, decreased the thrombin activity on a chromogenic substrate. Further, increasing concentrations of thrombin overcame the inhibitory effect of the patient's paraprotein. Thus, the patient's paraprotein appeared to possess antithrombin activity.
C3 Polymorphisms and Allograft Outcome in Renal Transplantation
Authors: Mira Varagunam, Muhammad M. Yaqoob, Bernd Döhler, Gerhard Opelz
Journal: New England Journal of Medicine (2009)

Complement activation plays a role in the development of chronic allograft nephropathy, a common cause of late allograft loss. The role of two complement component 3 (C3) allotypes, called C3F (fast) and C3S (slow) on the basis of their electrophoretic motility, in the long-term outcome of renal allografts remains controversial.We selected a random sample of 1147 donor and recipient pairs from the Collaborative Transplant Study DNA bank, and their DNA specimens were genotyped for the C3F and C3S alleles. The genotyping results were analyzed according to allograft outcome. Transplants were divided into four groups, according to the recipient and donor genotypes: SS recipient and FS or FF donor (the standard for comparison, since this combination has been reported to have the best outcome), SS recipient and donor, FS or FF recipient and SS donor, and FS or FF recipient and donor.Baseline characteristics of the four transplant groups were similar. The hazard ratios for allograft survival in the SS recipient and FS or FF donor group as compared with the other three groups (SS recipient and donor, FS or FF recipient and SS donor, and FS or FF recipient and donor) were not significant: 0.90 (95% confidence interval [CI], 0.7 to 1.14; P=0.33), 0.87 (95% CI, 0.65 to 1.16; P=0.33), and 0.89 (95% CI, 0.65 to 1.23; P=0.48), respectively. The four groups had similar patient-survival rates and similar cumulative rates of acute rejection and allograft dysfunction, as assessed by means of serum creatinine levels.Our results suggest that transplantation of FS or FF kidneys to SS recipients is not advantageous, possibly because chronic allograft nephropathy is a multifaceted disease involving the interplay of many biologic pathways.
A COMPARISON OF OCULAR MICROMETRIC AND PROJECTOSCOPIC METHODS OF ESTIMATING GROWTHS IN TISSUE CULTURES
Authors: Homer F. Swift, Johannes K. Moen, Ernst Vaubel
Journal: The Journal of Experimental Medicine (1934)

In estimating the increments of growth of tissue cultures and of comparative indices it is possible to use areas calculated from measurement of two axes made with an ocular micrometer in an ordinary microscope. On the assumption that the growths are approximately circular in outline the squares of their radii are used as the factors for comparison. Results obtained with this method agree fairly closely with those derived from projectoscopic drawings and planimetric measurements.