tbuckley/cabot-search huggingface dataset:
Epigenetic Alteration of <i>PRKCDBP</i> in Colorectal Cancers and Its Implication in Tumor Cell Resistance to TNFα-Induced Apoptosis
Authors: Jin-Hee Lee, Min-Ju Kang, Hye-Yeon Han, Min-Goo Lee, Seong-In Jeong, Byung-Kyu Ryu, Tae-Kyu Ha, Nam-Goo Her, Jikhyon Han, Sun Jin Park, Kil Yeon Lee, Hyo-Jong Kim, Sung-Gil Chi
Journal: Clinical Cancer Research (2011)

PRKCDBP is a putative tumor suppressor in which alteration has been observed in several human cancers. We investigated expression and function of PRKCDBP in colorectal cells and tissues to explore its candidacy as a suppressor in colorectal tumorigenesis.Expression and methylation status of PRKCDBP and its effect on tumor growth were evaluated. Transcriptional regulation by NF-κB signaling was defined by luciferase reporter and chromatin immunoprecipitation assays.PRKCDBP expression was hardly detectable in 29 of 80 (36%) primary tumors and 11 of 19 (58%) cell lines, and its alteration correlated with tumor stage and grade. Promoter hypermethylation was commonly found in cancers. PRKCDBP expression induced the G(1) cell-cycle arrest and increased cellular sensitivity to various apoptotic stresses. PRKCDBP was induced by TNFα, and its level correlated with tumor cell sensitivity to TNFα-induced apoptosis. PRKCDBP induction by TNFα was disrupted by blocking NF-κB signaling while it was enhanced by RelA transfection. The PRKCDBP promoter activity was increased in response to TNFα, and this response was abolished by disruption of a κB site in the promoter. PRKCDBP delayed the formation and growth of xenograft tumors and improved tumor response to TNFα-induced apoptosis.PRKCDBP is a proapoptotic tumor suppressor which is commonly altered in colorectal cancer by promoter hypermethylation, and its gene transcription is directly activated by NF-κB in response to TNFα. This suggests that PRKCDBP inactivation may contribute to tumor progression by reducing cellular sensitivity to TNFα and other stresses, particularly under chronic inflammatory microenvironment.
Clinical Features of Hematopoietic Malignancies and Related Disorders among Benzene-Exposed Workers in China
Authors: Martha S. Linet, Song Nian Yin, Lois B. Travis, Chin Yang Li, Zhi Nan Zhang, De Gao Li, Nathaniel Rothman, Gui Lan Li, Wong Ho Chow, Jennifer Donaldson, Mustafa Dosemeci, Sholom Wacholder, William J. Blot, Richard B. Hayes, Y. Z. Wang, T. R. Dai, X. J. Chao, Z. L. Jiang, W. U. Zhang, P. Z. Ye, Q. R. Kou, Y. H. Fan, X. C. Zhang, X. F. Lin, J. F. Meng, J. S. Zho
Journal: Environmental Health Perspectives (1996)

Previous occupational cohort studies of benzene-exposed workers have for the most part used only death certificates to validate diagnoses of workers developing leukemia and other hematopoietic and lymphoproliferative malignancies and related disorders (HLD). In a follow-up study of 74,828 benzene-exposed workers and a comparison group of 35,805 nonexposed workers from 12 cities in China, we sought to characterize clinicopathologically and to confirm diagnoses of all cases of HLD. Using medical records, laboratory hematology results, and histopathology, U.S. and Chinese expert hematopathologists, blinded to exposure status, carried out a detailed review using standardized evaluation forms. Key among the findings were a notable diversity of malignant and nonneoplastic hematopoietic and lymphoproliferative disorders, documentation of excess myelodysplastic syndromes among benzene workers, and widespread dyspoiesis involving all hematopoietic cell lines. As sophisticated clinicopathologic characterization and corresponding classification schemes for HLD become increasingly widespread, it is recommended that future epidemiologic investigations of benzene workers incorporate similarly detailed morphologic evaluation. In extending follow-up of this cohort of young workers, we will continue to use all available clinical, laboratory hematology, and pathology data as well as cytogenetic and biochemical markers to characterize various HLD outcomes. These careful surveillance mechanisms should also provide additional insight into carcinogenic mechanismsmore » of benzene and allow comparison of the molecular pathogenesis of HLD induced by benzene versus chemotherapy, radiation, or other exposure. 116 refs., 4 figs., 3 tabs.« less
PRESENT KEY PROBLEMS IN TUBERCULOSIS
Authors: EDGAR MAYER
Journal: JAMA (1942)

The sharpest controversy is now focused on three problems in tuberculosis:   Is a negative or a positive tuberculin reaction more desirable?  Are the lesions developing in recently exposed young adults of  or reinfection type?  From what point should one date the clinical incipience of tuberculosis?   With regard to these three questions, it is in the first place to be emphasized that they have arisen only recently and are the result of the epidemiologic conditions which have developed in our midst within the last generation.  Previously in most communities it was true for the vast majority of persons that they become positive tuberculin reactors by the time they reached adolescence; that, while primary infections occurred in childhood, progressive pulmonary tuberculosis developed mostly only in early adult age; that a latent interval of a decade usually elapsed between the time of the infections and the evidence of progressive
Expression of RANTES mRNA and protein in airways of patients with mild asthma.
Authors: N Berkman, V L Krishnan, T Gilbey, R Newton, B O'Connor, P J Barnes, K F Chung
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Chemoattractant cytokines (chemokines) such as RANTES, are potent chemoattractants for eosinophils, T lymphocytes, and monocyte/macrophages. We examined RANTES mRNA and protein expression in bronchial biopsies and bronchoalveolar lavage (BAL) cells from patients with mild asthma on beta 2-adrenergic agonist therapy only. Using quantitative polymerase chain reaction (PCR), mean RANTES starting cDNA was 110 +/- 18 fg/pg beta-actin in asthmatics compared with 33.7 +/- 11.0 fg/pg in normals (p < 0.003) but there was no significant difference in RANTES mRNA expression in BAL cells between the two groups. Immunohistochemical staining of cryostat sections of bronchial biopsies with an anti-RANTES antibody using peroxidase antiperoxidase method revealed constitutive staining in airway epithelial cells, airway smooth muscle, and subepithelial cells. However, there was no difference in the number of RANTES-staining cells between normal subjects and asthmatics despite significantly increased numbers of CD4+ T-cells, CD68+ macrophages, and MBP+ eosinophils in mucosal biopsies obtained from asthmatics. Double-staining revealed expression of RANTES in a proportion of CD3+ T lymphocytes. Thus, RANTES is constitutively expressed in the airways and RANTES mRNA is elevated in airways of patients with mild asthma, supporting a role for RANTES in normal and asthmatic airways.
Regulation of 17-AAG—induced apoptosis: role of Bcl-2, Bcl-xL, and Bax downstream of 17-AAG—mediated down-regulation of Akt, Raf-1, and Src kinases
Authors: Ramadevi Nimmanapalli, Erica O'Bryan, Deborah Kuhn, Hirohito Yamaguchi, Hong-Gang Wang, Kapil N. Bhalla
Journal: Blood (2003)
Histology of the postoperative stomach before and after diversion of bile.
Authors: P C Watt, J M Sloan, A Spencer, T L Kennedy
Journal: BMJ (1983)

Gastric biopsy specimens were taken in 33 patients before and after procedures to divert bile (construction of Roux loop in 19, closure of gastrojejunostomy in 14). Each biopsy specimen was assessed for dysplasia, intestinal metaplasia, atrophy, and gastritis, each variable being given a score ranging from 0 to 6. Patients were given preoperative and postoperative scores for each of these variables based on the average score of all preoperative or postoperative specimens. Comparison between preoperative and postoperative histology showed that there was no difference for gastritis, atrophy, or intestinal metaplasia. Patients who underwent closure of a gastrojejunostomy showed improvement in dysplasia that was not statistically significant. There was, however, a significant improvement in dysplasia in patients in whom a Roux loop was fashioned (p = 0.006) and in all patients taken together (p = 0.002). It was concluded that procedures that divert bile improve dysplasia but not other histological abnormalities in the stomach postoperatively.
Influence of ursodeoxycholate-enriched diet on liver tumor growth in HBV transgenic mice
Authors: M. Barone, E. Maiorano, R. Ladisa, R. Cuomo, A. Pece, P. Berloco, M.L. Caruso, A.M. Valentini, A. Iolascon, A. Di Leo, E. Ierardi, A. Francavilla
Journal: Journal of Hepatology (2003)
Passive smoking: Peer review and press release
Authors: R. M Davis
Journal: BMJ (2003)

Editor–The questions raised about the validity of the data reported by Enstrom and Kabat call into question the adequacy of the peer and editorial review of the paper at the BMJ .1 Apparently no one with special expertise in research on the health effects of passive smoking was involved in the review of this paper. In an area as complex as this–to which massive reports have been …
Transport of monoglucuronosyl and bisglucuronosyl bilirubin by recombinant human and rat multidrug resistance protein 2
Authors: Toshinori Kamisako, Inka Leier, Yunhai Cui, Jörg König, Ulrike Buchholz, Johanna Hummel-Eisenbeiss, Dietrich Keppler
Journal: Hepatology (1999)

The secretion of bilirubin conjugates from hepatocytes into bile represents a decisive step in the prevention of hyperbilirubinemia. The bilirubin conjugates, monoglucuronosyl bilirubin (MGB) and bisglucuronosyl bilirubin (BGB), were previously suggested to be endogenous substrates for the apical multidrug resistance protein (MRP2), a member of the adenosine triphosphate (ATP)-binding cassette family of transporters (symbol ABCC2), also termed canalicular multispecific organic anion transporter. We have characterized this ATP-dependent transport using membrane vesicles from human embryonic kidney (HEK) cells expressing recombinant rat as well as human MRP2. MGB and BGB, 3 H-labeled in the glucuronosyl moiety, were synthesized enzymatically with recombinant UDP-glucuronosyltransferase 1A1, and stabilized with ascorbate. Rates for ATP-dependent transport of MGB and BGB (0.5 μmol/L each) by human MRP2 were 183 and 104 pmol × mg protein −1 × min −1 , respectively. K m values were 0.7 and 0.9 μmol/L for human MRP2, and 0.8 and 0.5 μmol/L for rat MRP2, with MGB and BGB as substrates, respectively. Leukotriene C 4 and 17β-glucuronosyl estradiol, which are both known high-affinity substrates for human MRP2, inhibited [ 3 H]MGB transport with IC 50 values of 2.3 and 30 μmol/L, respectively. Cyclosporin A competitively inhibited human and rat MRP2-mediated transport of [ 3 H]MGB, with K i values of 21 and 10 μmol/L, respectively. Our results provide direct evidence that recombinant MRP2, cloned from rat as well as human liver, mediates the primary-active ATP-dependent transport of the bilirubin conjugates MGB and BGB.
Inhaled beclomethasone dipropionate downregulates airway lymphocyte activation in atopic asthma.
Authors: J W Wilson, R Djukanović, P H Howarth, S T Holgate
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

It is widely known that inhaled corticosteroids are highly efficacious in the prophylactic treatment of asthma, but the mechanism of this action is not known. In this study we have investigated the effect of 6 wk of therapy with inhaled beclomethasone dipropionate (BDP; daily dose 2,000 micrograms for 2 wk and 1,000 micrograms for 4 wk) in a group of symptomatic individuals with asthma on clinical and physiologic indices of disease activity and on T cell numbers and state of activation in peripheral blood and bronchoalveolar lavage (BAL). This course of treatment had a marked effect of improving all indices of disease activity including symptom scores, morning peak expiratory flow (PEF), variation in PEF, and methacholine PC20 (from a geometric mean of 0.62 to 4.6 mg/ml) but did not alter the total numbers of T cells, identified by the CD3 receptor, or the CD4+ and CD8+ subsets when analyzed in peripheral blood or BAL using flow cytometry. However, BDP treatment had a marked effect in reducing the expression of the activation markers CD25 and HLA-DR (p < 0.02) in T cells recovered by BAL in which these markers were upregulated. A small but significant (p < 0.02) downregulation of HLA-DR expression was also observed on peripheral blood T cells. These data add to the view that T cells are upregulated in the airways of individuals with asthma and are susceptible to inhibition by topical corticosteroids.
INFLUENCE OF PARTICIPATION IN CLINICAL TRIALS ON OUTCOMES AFTER CAROTID ARTERY STENTING - RESULTS FROM THE CAROTID ARTERY REVASCULARIZATION AND ENDARTERECTOMY (CARE) REGISTRY
Authors: Robert W. Yeh, Sahil A. Parikh, Kevin F. Kennedy, Rahul Sakhuja, John A. House, Kenneth Rosenfield
Journal: Journal of the American College of Cardiology (2010)
Disclosure of Industry Payments to Physicians
Authors: Robert Steinbrook
Journal: New England Journal of Medicine (2008)

Most physicians in the United States have financial relationships with industry, ranging from the acceptance of meals to the receipt of large sums of money for consulting, speaking, or conducting research.1,2 Within the next several years, the manufacturers of drugs, medical devices, and medical supplies that are paid for by Medicare, Medicaid, or the State Children's Health Insurance Program may be required to report publicly many of these gifts and payments; the information would be made available in a “clear and understandable” format on a searchable government Web site. Public reporting would be mandated by the Physician Payments Sunshine . . .
Response to Letters Regarding Article, “Evidence for Statin Pleiotropy in Humans: Differential Effects of Statins and Ezetimibe on Rho-Associated Coiled-Coil Containing Protein Kinase Activity, Endothelial Function, and Inflammation”
Authors: Ping-Yen Liu, James K. Liao, Yen-Wen Liu, Li-Jen Lin, Jyh-Hong Chen
Journal: Circulation (2009)
Proposed Insurance Scheme
Authors: H. J. Houghton
Journal: BMJ (1965)

MEDIBCAISHRNA,The spleen may remain palpable in glandular fever for ten weeks4 and it has also been recorded as persisting in a child aged 6 weeks for two months.5The spleen in glandular fever is very soft and very friable, and it is apparent that spontaneous rupture can occur and even more so that minimal injury may produce rupture.In the case report by Spink' spontaneous rupture was considered to be due mainly to pressure from within the abdomen and not from pressure without.The patient in that case had denied any injury.
Earnings of G.P.s and Hospital Doctors
Authors: A. R. Prest
Journal: BMJ (1973)

JouRNAL 28 juLY 1973 already being made, and I would anticipate a successful outcome in due course.(2) So far as women doctors are con- cerned, they are in an unusual position in that for all service prior to March 1972 they will on retirement receive a substantial lump sum in lieu of a widower's pension.This lump sum is not received by a mar- ried man and pays for a half-pension for his widow.In the vast majority of cases the lump sum, received by the woman doctor and properly used, is worth more to the possible widower than the alternative pen- sion which might have been paid on the death of the woman doctor.(3) All this applies to service prior to March 1972, and the situation is quite different for service after March 1972, since for this the lump payment will not be de-
Leveling the Field — Ensuring Equity through National Health Care Reform
Authors: Bruce Siegel, Lea Nolan
Journal: New England Journal of Medicine (2009)

The United States is in the midst of a profound demographic transition. By 2050, non-Hispanic whites will account for less than half the U.S. population and members of racial and ethnic minority groups will be in the majority. This shift is also reflected in the fact that the United States is now home to at least 20 million people who have low proficiency in the English language. Although there are differences among minority groups, all these populations face special challenges. Members of minority groups have higher rates of disease, poorer health, and more limited access to care than their white . . .
Metastatic Choriocarcinoma With Tumor Thrombus in the Right Atrium and Pulmonary Vessels
Authors: Madhavi Tripathi, Maria M. D'Souza, Jyotika Jain, Madhur Srivastava, Abhinav Jaimini, Nikunj Jain, Sarika Bansal, Rajnish Sharma, Anupam Mondal
Journal: Clinical Nuclear Medicine (2009)

We report the case of an asymptomatic 38-year-old woman with persistent choriocarcinoma, based on the results of F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET/CT) followed by CT pulmonary angiography, a diagnosis of metastatic right atrial tumor thrombus with pulmonary tumor thromboemboli was made. The patient underwent aggressive salvage chemotherapy with a combination of 5 drugs (ifosfamide, cisplatin, etoposide, vinblastine, and bleomycin) and responded to therapy which was objectively documented by the F-18 FDG PET/CT imaging. Thus FDG-PET/CT is a useful modality for demonstrating metastatic tumor thrombi noninvasively, mapping the extent of metastasis and assessing the response to therapy objectively.
<b><i>H2-Ea</i></b>Deficiency Is a Risk Factor for Bleomycin-Induced Lung Fibrosis in Mice
Authors: Min Du, Roxanna A. Irani, David N. Stivers, Sang-Joon Lee, Elizabeth L. Travis
Journal: Cancer Research (2004)

Abstract Pulmonary fibrosis is a significant complication in cancer patients when treated by radiation, e.g., thoracic malignant diseases, or chemotherapeutic agents. Bleomycin is one of the primary drugs used to treat testicular cancer, but the incidence of significant pulmonary fibrosis limits the dose. It is known that susceptibility to bleomycin-induced pulmonary fibrosis is a heritable trait controlled by multiple genes, none of which, however, are yet known. In this study, we used expression profiling and genetic analysis in mouse models of bleomycin-induced pulmonary fibrosis and identified MHC class II antigen Eα (H2-Ea) as a risk factor for this disease. We found that a loss-of-function deletion in the H2-Ea gene was linked to susceptibility. A functional test of H2-Ea in transgenic mice showed 100% survival in the transgenic mice compared with 53% in C57BL/10J mice and significantly decreased pulmonary fibrosis from 16.42% (C57BL/10J) to 5.76% (transgenic; P = 1.20e−8). These results show that H2-Ea expression protects mice from bleomycin-induced pulmonary fibrosis, which implicates H2-Ea as a candidate susceptibility gene for pulmonary fibrosis.
INHERITANCE OF PERONEAL ATROPHY
Authors: MADGE THURLOW MACKLIN
Journal: JAMA (1926)

Although the literature contains many references to cases of peroneal atrophy, very few records deal with it from the standpoint of its inheritance. It is with that aspect of the question that the present paper deals. <h3>CLINICAL DESCRIPTION OF CASE</h3> A. P., a man, aged 22, came to one of us (J. T. B.) for professional advice. Clinical examination revealed that he is suffering from peroneal atrophy. Figures 1, 2, 3 and 4 show the characteristic atrophy of the peroneal and calf muscles, in contrast to the normal musculature of the trunk, face and arms. The thighs immediately above the knees are wasted, but this is probably due to disuse. The skin over the thighs is warm and normal in color and texture; that over the legs is cold, cyanotic and slightly roughened. Between the two areas there is a distinct line of demarcation just at the knee, best seen
Comparison of black and white patients attending hypertension clinics in England.
Authors: A D Munro-Faure, L J Beilin, C J Bulpitt, E C Coles, C T Dollery, J S Gear, G Harper, B F Johnson
Journal: BMJ (1979)

Reports suggest that hypertension and death due to hypertensive disease are commoner among black than among white people. One hundred and thirty-five black patients attending hypertension clinics at three English hospitals were compared with age-, sex-, and clinicmatched white patients. The black women had higher blood pressures and weighed more than the white women, but there were no differences between the men. The black patients had not increased risk from family, obstetric, or smoking history. Proteinuria and nocturia were more common in black patients while urinary infections were less common. Heart size and left ventricular voltage were greater in black patients. Haemoglobin and plasma cholesterol and triglyceride concentrations were smaller and serum globulin concentration greater in black patients. No difference in response to treatment, attributable to race, was observed during the period of clinic attendance, which averaged 1.7 years. There was a slightly greater rate of default among black men during the first year of attendance.
Renin Profiles
Authors: Norman M. Kaplan
Journal: JAMA (1977)

ALL hypertension cannot be neatly divided into three renin levels—low, normal, and high—but the observant clinician cannot help but be impressed with the charm and simplicity offered by renin profiling.<sup>1,2</sup>The profile is attractive because it brings some order to the unstructured mosaic of essential hypertension. Unfortunately, the etiologic, prognostic, and therapeutic implications of renin profiling have not held up under scrutiny. The "volume-vasoconstriction" model for the maintenance of hypertension does not conform to actual hemodynamic measurements made in patients.<sup>3</sup>The prognostic promises of low renin levels have not been fulfilled,<sup>4</sup>and the choosing of therapy based on renin status does not appear to work.<sup>5</sup> Renin profiling, nonetheless, has a place in clinical hypertension, though a much more limited one than its proponents advocate. This review will consider briefly the problems with the promises made for renin profiling and then offer guidelines for the practitioner in
Psychological Treatment of Patients with Chronic Toxic Encephalopathy: Lessons from Studies of Chronic Fatigue and Whiplash
Authors: Moniek S.E. van Hout, Ellie M. Wekking, Ina J. Berg, Betto G. Deelman
Journal: Psychotherapy and Psychosomatics (2003)

&lt;i&gt;Background:&lt;/i&gt; Chronic toxic encephalopathy (CTE), which can result from long-term exposure to organic solvents, is characterized by problems of attention and memory, fatigue and affective symptoms. There is little experience with (neuro)psychological treatment in this patient group. We reviewed treatment outcome studies of CTE and comparable syndromes, namely, chronic whiplash-associated disorder (WAD) and chronic fatigue syndrome (CFS), with a view to providing recommendations for the psychological treatment of patients with CTE. &lt;i&gt;Methods:&lt;/i&gt; PubMed and PsychLIT were systematically searched and reference lists of retrieved articles were studied. The articles were classified according to study design and level of evidence. &lt;i&gt;Results:&lt;/i&gt; The studies of CFS provided high-level evidence for the effectiveness of cognitive-behavior therapy (CBT) in challenging dysfunctional cognitions regarding the effectiveness of rest and in stimulating graded activity. The studies of WAD were methodologically weaker, and most evaluated a combination of CBT and graded activity training. There was some evidence that changing fatigue- or pain-related behaviors may result in cognitive improvement. Two uncontrolled studies of CTE evaluated cognitive rehabilitation techniques but yielded inconsistent findings. &lt;i&gt;Conclusions:&lt;/i&gt; CBT techniques focusing on changing illness attributions and on stimulating graded activity might be useful for patients with CTE, diminishing fatigue-related problems of concentration and memory. Future studies should evaluate whether cognitive deficits of CTE patients as a result of neurotoxic effects of exposure should be treated by cognitive rehabilitation.