tbuckley/cabot-search huggingface dataset:
Impact of Concordant and Discordant Bone Marrow Involvement on Outcome in Diffuse Large B-Cell Lymphoma Treated With R-CHOP
Authors: Laurie H. Sehn, David W. Scott, Mukesh Chhanabhai, Brian Berry, Anna Ruskova, Leanne Berkahn, Joseph M. Connors, Randy D. Gascoyne
Journal: Journal of Clinical Oncology (2011)

Purpose In diffuse large B-cell lymphoma (DLBCL), prior studies suggest that concordant bone marrow involvement with DLBCL portends a poorer prognosis, whereas discordant bone marrow involvement with small B-cell lymphoma does not. We examined the significance of bone marrow involvement in patients treated in the current era of therapy including rituximab. Patients and Methods We performed a retrospective analysis of the prognostic impact of bone marrow involvement in an unselected population of patients with newly diagnosed DLBCL treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in British Columbia and Auckland, New Zealand, with complete clinical information and evaluable staging bone marrow biopsies. Results In total, 795 patients were identified. Six hundred seventy (84.3%) of 795 had a negative bone marrow, 67 patients (8.4%) had concordant and 58 (7.3%) had discordant involvement. Median follow-up was 41 months (range, 1 to 115). Progression-free survival (PFS) was inferior in those with concordant (P &lt; .001) and discordant (P = .019) involvement while overall survival (OS) was inferior in those with concordant involvement (P &lt; .001) only. In a multivariate analysis controlling for the International Prognostic Index (IPI) score, concordant involvement remained an independent predictor of PFS (P &lt; .001) and OS (P = .007). Discordant involvement was associated with older age, elevated lactate dehydrogenase, advanced stage, and increased number of extranodal sites and was not a negative prognostic factor independent of the IPI score. Conclusion The negative prognostic impact of discordant involvement is adequately represented by the IPI score, while the risk with concordant involvement is greater than that encompassed by this predictor. The results emphasize the need for accurate staging assessment of bone marrow involvement in DLBCL.
The preferentially expressed antigen in melanoma (PRAME) inhibits myeloid differentiation in normal hematopoietic and leukemic progenitor cells
Authors: Vivian G. Oehler, Katherine A. Guthrie, Carrie L. Cummings, Kathleen Sabo, Brent L. Wood, Ted Gooley, Taimei Yang, Mirjam T. Epping, Yaping Shou, Era Pogosova-Agadjanyan, Paula Ladne, Derek L. Stirewalt, Janis L. Abkowitz, Jerald P. Radich
Journal: Blood (2009)
In vivo gene transfection with heat shock protein 70 enhances myocardial tolerance to ischemia-reperfusion injury in rat.
Authors: K Suzuki, Y Sawa, Y Kaneda, H Ichikawa, R Shirakura, H Matsuda
Journal: Journal of Clinical Investigation (1997)

Heat shock protein 70 (HSP70) has been reported to be involved in the myocardial self-preservation system. To obtain the evidence that HSP70 plays a direct role in the protection from myocardial ischemia-reperfusion injury, rat hearts were transfected with human HSP70 gene by intracoronary infusion of hemagglutinating virus of Japan (HVJ)-liposome containing human HSP70 gene. The control hearts were infused with HVJ-liposome without the HSP70 gene. The hearts from whole-body heat-stressed or nontreated rats were also examined. Western blot and immunohistochemical analysis showed that apparent overexpression of HSP70 occurred in the gene transfected hearts and that gene transfection might be more effective for HSP70 induction than heat stress. In Langendorff perfusion, better functional recovery as well as less creatine phosphokinase leakage after ischemia were obtained in the gene transfected hearts with HSP70 than in the control or nontreated hearts. Furthermore, the gene transfected hearts showed better functional recovery than the heat-stressed hearts. These results indicated that overexpressed HSP70 plays a protective role in myocardial injury, suggesting the possibility that gene transfection with HSP70 may become a novel method for myocardial protection through enforcing the self-preservation systems.
Stable and Unstable Malaria Hotspots in Longitudinal Cohort Studies in Kenya
Authors: Philip Bejon, Thomas N. Williams, Anne Liljander, Abdisalan M. Noor, Juliana Wambua, Edna Ogada, Ally Olotu, Faith H. A. Osier, Simon I. Hay, Anna Färnert, Kevin Marsh
Journal: PLoS Medicine (2010)

Philip Bejon and colleagues document the clustering of malaria episodes and malarial parasite infection. These patterns may enable future prediction of hotspots of malaria infection and targeting of treatment or preventive interventions.
Immunization Levels Among Premature and Low-Birth-Weight Infants and Risk Factors for Delayed Up-to-Date Immunization Status
Authors: R L Davis, D Rubanowice, H R Shinefield, N Lewis, D Gu, S B Black, F DeStefano, P Gargiullo, J P Mullooly, R S Thompson, R T Chen
Journal: JAMA (1999)

NFANTS ARE IMMUNOCOMPROmised compared with older children and adults.Immunoglobulin G (IgG) is transferred transplacentally to the fetus, and intrauterine levels of IgG in the developing infant correlate with gestational age.2][3] Premature infants who contract pertussis are also at increased risk for severe infections, for hypoxic episodes with paroxysmal coughing, and for dying or developing long-term lung damage after infection.To prevent morbidity and mortality due to vaccinepreventable diseases, including pertussis, the Advisory Committee on Infectious Diseases has recommended that premature infants receive immunizations at the same chronological
Should we be using statistics to define disease?
Authors: D. M Mannino
Journal: Thorax (2008)

“Don’t worry about the physiology test—if everybody fails, everybody passes”, Anonymous, Jefferson Medical College, Fall 1977.

The first few months of medical school caused anxiety in most students, who typically went from environments where they were well above the “norm” in their classes to one in which they were just average. At the same time, the volume and difficulty of the material one was expected to master increased dramatically, compared with undergraduate studies. The one hope students could hold onto was that tests were graded “on the curve” and as long as you did better than the bottom 5% of the class (the lower limit of normal (LLN)) you would pass. This is the origin of the phrase “if everyone fails, everyone passes”. At the time, unbeknownst to the students, there was a push in our medical school to move towards a more standardised minimal passing grade of, somewhat ironic to this discussion, 70%, that would allow better comparison between classes and schools. The argument here was that if, in fact, everyone failed (ie, scored less than the minimum passing grade), even if that was “normal”, it was not good.

The conflict between what is statistically “normal” and statistically “abnormal”, and how these are defined, is central to a current controversy in the world of respiratory medicine. On one side of this debate is the idea that “normal” people lose lung function as they age, and because of the “normal” loss of elastic tissue in the lung, the forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) will also decrease with aging. Defenders of this position state that the definition of “abnormal” needs to …
Airway response to deep inspiration: role of nitric oxide
Authors: R.H. Brown, W. Mitzner
Journal: European Respiratory Journal (2003)

Deep inspirations (DI) have been shown to have both bronchoprotective and bronchodilator effects in healthy subjects. The bronchodilator effects of a DI appear to be impaired in asthmatics compared with healthy subjects. This study investigated the role of nitric oxide (NO) in the bronchodilator role of a DI. In five anaesthetised and ventilated dogs, high-resolution computed tomography was used to measure the changes in airway size after a small (25 cmH 2 O) and large (45 cmH 2 O) DI before and after administering N G -nitro‐l‐arginine methyl ester to block NO synthesis. The depth of the inspiratory manoeuvre during a deep inspiration determined the subsequent qualitative behaviour of the airway response. Inflation to relatively high pressure resulted in airway dilation, whereas one to lower pressure leads to airway constriction. When N G -nitro‐L‐arginine methyl ester was administered, both a large and a small deep inspiration resulted in subsequent airway constriction. These results support the idea that nitric oxide may be a potential bronchoprotective agent in the airways.
HOX11L2 expression defines a clinical subtype of pediatric T-ALL associated with poor prognosis
Authors: Paola Ballerini, Annick Blaise, Maryvonne Busson-Le Coniat, Xin Ying Su, Jessica Zucman-Rossi, Mircea Adam, Jacqueline van den Akker, Christine Perot, Beatrice Pellegrino, Judith Landman-Parker, Luc Douay, Roland Berger, Olivier A. Bernard
Journal: Blood (2002)
Translation Inhibitor Pdcd4 Is Targeted for Degradation during Tumor Promotion
Authors: Tobias Schmid, Aaron P. Jansen, Alyson R. Baker, Glenn Hegamyer, John P. Hagan, Nancy H. Colburn
Journal: Cancer Research (2008)

Inactivation of tumor suppressors is among the rate-limiting steps in carcinogenesis that occur during the tumor promotion stage. The translation inhibitor programmed cell death 4 (Pdcd4) suppresses tumorigenesis and invasion. Although Pdcd4 is not mutationally inactivated in human cancer, the mechanisms controlling Pdcd4 inactivation during tumorigenesis remain elusive. We report that tumor promoter 12-O-tetradecanoylphorbol-13-acetate exposure decreases protein levels of Pdcd4 in mouse skin papillomas and keratinocytes as well as in human HEK293 cells. This decrease is attributable to increased proteasomal degradation of Pdcd4 and is mediated by protein kinase C-dependent activation of phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin-p70(S6K) and mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK signaling. Both Akt and p70(S6K) phosphorylate Pdcd4, allowing for binding of the E3-ubiquitin ligase beta-TrCP and consequently ubiquitylation. MEK-ERK signaling on the other hand facilitates the subsequent proteasomal degradation. We further show that Pdcd4 protein levels in vivo are limiting for tumor formation, establishing Pdcd4 as a haploinsufficient tumor suppressor in Pdcd4-deficient mice. Thus, because endogenous Pdcd4 levels are limiting for tumorigenesis, inhibiting signaling to Pdcd4 degradation may prove a valid strategy for cancer prevention and intervention.
Receptor-mediated cardioprotective effects of endogenous adenosine are exerted primarily during reperfusion after coronary occlusion in the rabbit.
Authors: Z Q Zhao, S McGee, K Nakanishi, C F Toombs, W E Johnston, M S Ashar, J Vinten-Johansen
Journal: Circulation (1993)

BACKGROUND We hypothesized that: (1) endogenous adenosine released during ischemia/reperfusion reduces infarct size and preserves postischemic myocardial blood flow by receptor-mediated mechanisms and (2) this cardioprotection is exerted predominantly during reperfusion. METHODS AND RESULTS Sixty-one anesthetized open-chest rabbits subjected to 30 minutes of coronary occlusion and 120 minutes of reperfusion were randomized to six groups: group 1, saline (Vehicle) (n = 10) to allow receptor interaction of endogenous adenosine (Ado) during ischemia/reperfusion; group 2, Ado-receptor blockade during both ischemia and reperfusion with intravenous 8-p-sulfophenyltheophyl-line (10 mg/kg) (SPTIR, n = 10); group 3, Ado-receptor blockade in multiple doses during both ischemia and reperfusion (MSPTIR, n = 11); group 4, blockade during reperfusion (SPTR, n = 10); group 5, blockade during reperfusion with PD115,199 (6 mg/kg) (PDR, n = 10); and group 6, blockade after 30 minutes of reperfusion (SPT30R, n = 10) to allow adenosine receptor interaction during early reperfusion. Transmural myocardial blood flow in the area at risk (Ar) (15-microns radiolabeled microspheres) was reduced by 96.7% in all groups, from 137.9 +/- 15.5 to 4.5 +/- 1.4 mL.min-1 x 100 g-1 (P &lt; .001). MSPTIR, SPTIR, and SPTR significantly attenuated reactive hyperemia at 15 minutes of reperfusion (144 +/- 18, 141 +/- 22, and 144 +/- 20 mL.min-1 x 100 g-1, respectively) compared with Vehicle (257 +/- 40 mL.min-1 x 100 g-1, P &lt; .05). This attenuation was more pronounced in the necrotic zone than in the nonnecrotic zone. Reactive hyperemia at 15 minutes of reperfusion in SPT30R group was comparable to the Vehicle group. At 120 minutes of reperfusion, blood flow in Ar was significantly less in MSPTIR (77 +/- 10), SPTIR (82 +/- 9), and SPTR (80 +/- 11) compared with Vehicle (140 +/- 12) and SPT30R (105 +/- 24 mL.min-1 x 100 g-1). Infarct size (by triphenyltetrazolium chloride), expressed as a percent of Ar, was largest in the multiple-dose group with blockade during both ischemia and reperfusion (MSPTIR, 51.9 +/- 2.3%) and was significantly increased also in single-dose SPTIR (39.1 +/- 2.2%) compared with 25.7 +/- 1.7% in the Vehicle group (P &lt; .05). Ado-receptor blockade only during reperfusion was associated with 14% smaller infarct size in the SPTR group than the MSPTIR group (P &lt; .05). In contrast, Ado-receptor blockade after 30 minutes of reperfusion (SPT30R) did not increase infarct size (27.9 +/- 2.2%), which was comparable to infarct size in the Vehicle group. CONCLUSIONS We conclude that: (1) endogenous adenosine released from the myocardium during ischemia/reperfusion reduces infarct size by receptor-mediated mechanisms and (2) Ado-mediated cardioprotection is most pronounced during the early phase of reperfusion.
Ablative fractional laser therapy as treatment for Becker nevus: A randomized controlled pilot study
Authors: Arne A. Meesters, Bas S. Wind, Marije W. Kroon, Albert Wolkerstorfer, J.P. Wietze van der Veen, Ludmila Nieuweboer-Krobotová, Allard C. van der Wal, Jan D. Bos, Johan F. Beek
Journal: Journal of the American Academy of Dermatology (2011)
LSC 2012 abstract - Activation of Wnt/β-catenin signaling promotes lung epithelial repair in emphysema
Authors: J. Callegari, K. Mutze, M. Königshoff
Journal: European Respiratory Journal (2012)

Emphysema is characterized by airspace enlargement, tissue destruction and reduced Wnt signaling. Wnt/β-catenin activation attenuated experimental emphysema. Here, we aim to elucidate the mechanism of Wnt/β-catenin induced alveolar epithelial cell repair in vitro and in vivo.

Alveolar epithelial type II cells were isolated from untreated (ATIIc) or elastase treated (ATIIe) C57BL/6 mice at day 3, 7 and 14 with similar purity (>94%) and viability (>92%). ATIIe cells depicted increased cell numbers (i.e. 6,07±1,62x106 ATIIe and 3,39±0,86x106 ATIIc, day14), and significantly reduced expression of the Wnt target genes Axin2, LEF1 and LRP6 (i.e. LRP6 0,29±1,42 ATIIe vs. 2,38±0,56 ATIIc, day7) as determined by qRT-PCR. Freshly isolated ATIIe cells exhibited increased apoptosis susceptibility (Annexin V/PI staining). Live cell imaging of cultured ATII cells revealed altered ATIIe cell morphology and migratory behavior. Wnt activation of ATII cells by rWnt3a led to increased expression of Wnt target genes (i.e. Axin2 -2,15±0,12 rWnt3a for 24h vs. -5,18±0,29 control), epithelial markers SPC, TJP1, and Occludin, and increased proliferative capacity (BrdU).

Primary ATIIe cells exhibited reduced Wnt/β-catenin activity and altered functional capacity. Wnt/β-catenin activation led to increased epithelial marker expression and stabilized ATII cell monolayers. Thus, activation of Wnt/β-catenin is a suitable tool to increase alveolar epithelial cell repair capacity in pulmonary emphysema.
Socioeconomic gradient in morbidity and mortality in people with diabetes: cohort study findings from the Whitehall study and the WHO multinational study of vascular disease in diabetes
Authors: N. Chaturvedi, J. Jarrett, M. J Shipley, J. H Fuller
Journal: BMJ (1998)

<b>Objectives:</b> To assess whether the inverse socioeconomic mortality gradient observed in the general population persists in diabetic people. <b>Design:</b> The Whitehall cohort study and the London cohort of the WHO multinational study of vascular disease in diabetes. <b>Setting:</b> London. <b>Subjects:</b> 17 264 male civil servants (17 046 without diabetes, 218 with diabetes) aged 40–64 examined in 1967-9, and 300 people with diabetes aged 35–55 from London clinics examined in 1975-7. Both cohorts were followed up until January 1995. <b>Main outcome measures:</b> Mortality from all causes, cardiovascular disease, and ischaemic heart disease. <b>Results:</b> In both cohorts people in the lower social groups were older, had higher blood pressure, and were more likely to smoke. In the Whitehall study, the prevalence of heart disease was higher in the lowest social group compared with the highest group, by 6% among non-diabetic people (P=0.0001) and by 14% among diabetic subjects (P=0.02). In the WHO study proteinuria was more common in the lowest social group compared with the highest (27% <i>v</i> 15%, P=0.01), as was retinopathy (54% <i>v</i> 48%, P=0.5). There was a clear socioeconomic gradient in all cause mortality in both cohorts, with death rates being about twice as high in the lowest compared with the highest social groups. In the Whitehall study this gradient was similar in both diabetic and non-diabetic subjects, and it persisted for mortality from cardiovascular disease and from ischaemic heart disease. About half of the increased risk of death in the lowest social group was accounted for by blood pressure and smoking. <b>Conclusions:</b> We confirm the existence of an inverse socioeconomic mortality gradient in diabetic people and suggest that this is largely due to conventional cardiovascular risk factors. <h3>Key messages</h3> People in lower social classes tend to have higher mortality than those in higher classes, but a Finnish study found no such socioeconomic gradient in mortality among diabetic people In response to this research we examined mortality in two large studies with 20 year follow up of 17 264 Whitehall civil servants (218 with diabetes) and 300 patients attending diabetes clinics in London Mortality was twice as high in diabetic people in the lowest socioeconomic groups as in those in the highest groups This difference was largely due to higher rates of smoking and high blood pressure in the lowest social groups, while blood glucose concentration had little impact on the relation These results emphasise the importance of improving conventional cardiovascular risk factors and reducing social inequality for reducing mortality in diabetic people
PROTECTIVE AND CELLULAR IMMUNE RESPONSES TO IDIOTYPIC DETERMINANTS ON CELLS FROM A SPONTANEOUS LYMPHOMA OF NZB/NZW F1 MICE
Authors: Susumu Sugai, Donald W. Palmer, Norman Talal, Isaac P. Witz
Journal: The Journal of Experimental Medicine (1974)

A spontaneous lymphoma (141) producing monoclonal IgM is established in NZB/NZW F(1) (B/W) mice who spontaneously develop an autoimmune disease. Idiotypic determinants of 141 IgM are present on the lymphoma cell surface as shown by indirect immunofluorescence and specific cytotoxicity with rabbit anti-idiotypic antiserum. Fluorescence and cytotoxicity are inhibited by 141 IgM but not by 104E IgM, a monoclonal IgM produced by a BALB/c plasmacytoma. Immunization of B/W mice with 141 IgM before transplantation of lymphoma 141 confers protective immunity. No such protection occurs after immunization with 104E IgM or other unrelated proteins. Protected mice contain spleen cells cytotoxic for 141 lymphoma cells. This cytotoxicity is blocked by incubation of spleen cells with 141 IgM but not with 104E IgM. Moreover, splenic lymphocytes from protected mice are stimulated to synthesize DNA by 141 IgM but not by 104E IgM. These results suggest that specific cellular immune responses to idiotypic determinants may participate in the observed protection against challenge with the corresponding B-cell tumor.
Pulmonary sarcoidosis with an alveolar radiographic pattern.
Authors: J P Battesti, G Saumon, D Valeyre, J Amouroux, B Pechnick, D Sandron, R Georges
Journal: Thorax (1982)

Thirty-three cases of sarcoidosis (4.4% of 746 patients) showed an alveolar radiological pattern. A study of pulmonary function was carried out in 25 patients and compared with that of 46 patients with the interstitial radiological type of sarcoidosis. Twenty-two cases have been followed up from one to six years after the initial examination. The radiographic lesions were most often bilateral and included nodules greater than 15 mm with ill-defined margins or diffuse, infiltrative, non-retractile opacities with fluffy margins. Bilateral mediastinal lymph nodes were present in 27 patients. In 20 patients an associated reticulation was found on radiography. In four patients an open lung biopsy was done. The granulomatous nodules were identical to those found in other forms of sarcoidosis, although they were more confluent in the affected areas. Clinical and functional findings did not differ from those in the more common forms of sarcoidosis. Alveolar sarcoidosis has a sudden course. The alveolar radiological patterns always disappeared, with or without steroid treatment, while reticular patterns persisted in four patients. Rapid radiological changes were observed. Some functional abnormalities persisted in cases that were followed. It is concluded that alveolar sarcoidosis is a distinct acute form of sarcoidosis.
Prevalence of seasonal affective disorder in Alaska
Authors: J M Booker, C J Hellekson
Journal: American Journal of Psychiatry (1992)

The goals of this study are to provide estimates of the prevalence of seasonal affective disorder in Alaska, to examine sociodemographic correlates, and to evaluate the relation between seasonal affective disorder and general depression.A random sample of 283 residents of Fairbanks who had lived in Alaska for 3 years or more were interviewed with the Seasonal Pattern Assessment Questionnaire and the Center for Epidemiologic Studies Depression Scale (CES-D Scale).Twenty-six (9.2%) of the subjects met diagnostic criteria for seasonal affective disorder, one of the highest figures yet reported. These cyclic winter affective disorders occurred more often in women than men (ratio = 3:2) and were less prevalent among residents who were older than 40 years of age. Assessment of depression with the CES-D Scale supported the diagnostic classification of respondents and the differentiation of seasonal affective disorder from other depression.This study supports the conclusions that seasonal affective disorder is prevalent in northern populations and that sex and age may represent the major risk factors that differentiate it from the general experience of depression in northern communities.
SERUM PROTEINS AND LIVER FUNCTION IN EXFOLIATIVE DERMATITIS.
Authors: A. TICKNER, A. BASIT
Journal: British Journal of Dermatology (1960)

Journal Article SERUM PROTEINS AND LIVER FUNCTION IN EXFOLIATIVE DERMATITIS. Get access A. TICKNER, A. TICKNER Division of Chemical Pathology, St. John's Hospital for Diseases of the Skin, Homerton Grove, London, E.9 Search for other works by this author on: Oxford Academic Google Scholar A. BASIT A. BASIT Division of Chemical Pathology, St. John's Hospital for Diseases of the Skin, Homerton Grove, London, E.9 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 72, Issue 4, 1 April 1960, Pages 138–141, https://doi.org/10.1111/j.1365-2133.1960.tb13861.x Published: 01 April 1960