tbuckley/cabot-search huggingface dataset:
Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in Postmenopausal Women
Authors: Rowan T. Chlebowski, Garnet L. Anderson, Margery Gass, Dorothy S. Lane, Aaron K. Aragaki, Lewis H. Kuller, JoAnn E. Manson, Marcia L. Stefanick, Judith Ockene, Gloria E. Sarto, Karen C. Johnson, Jean Wactawski-Wende, Peter M. Ravdin, Robert Schenken, Susan L. Hendrix, Aleksandar Rajkovic, Thomas E. Rohan, Shagufta Yasmeen, Ross L. Prentice, for the WHI Investigators
Journal: JAMA (2010)

<h3>Context</h3>In the Women's Health Initiative randomized, placebo-controlled trial of estrogen plus progestin, after a mean intervention time of 5.6 (SD, 1.3) years (range, 3.7-8.6 years) and a mean follow-up of 7.9 (SD, 1.4) years, breast cancer incidence was increased among women who received combined hormone therapy. Breast cancer mortality among participants in the trial has not been previously reported.<h3>Objective</h3>To determine the effects of therapy with estrogen plus progestin on cumulative breast cancer incidence and mortality after a total mean follow-up of 11.0 (SD, 2.7) years, through August 14, 2009.<h3>Design, Setting, and Participants</h3>A total of 16 608 postmenopausal women aged 50 to 79 years with no prior hysterectomy from 40 US clinical centers were randomly assigned to receive combined conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo pill. After the original trial completion date (March 31, 2005), reconsent was required for continued follow-up for breast cancer incidence and was obtained from 12 788 (83%) of the surviving participants.<h3>Main Outcome Measures</h3>Invasive breast cancer incidence and breast cancer mortality.<h3>Results</h3>In intention-to-treat analyses including all randomized participants and censoring those not consenting to additional follow-up on March 31, 2005, estrogen plus progestin was associated with more invasive breast cancers compared with placebo (385 cases [0.42% per year] vs 293 cases [0.34% per year]; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.07-1.46; P = .004). Breast cancers in the estrogen-plus-progestin group were similar in histology and grade to breast cancers in the placebo group but were more likely to be node-positive (81 [23.7%] vs 43 [16.2%], respectively; HR, 1.78; 95% CI, 1.23-2.58; P = .03). There were more deaths directly attributed to breast cancer (25 deaths [0.03% per year] vs 12 deaths [0.01% per year]; HR, 1.96; 95% CI, 1.00-4.04; P = .049) as well as more deaths from all causes occurring after a breast cancer diagnosis (51 deaths [0.05% per year] vs 31 deaths [0.03% per year]; HR, 1.57; 95% CI, 1.01-2.48; P = .045) among women who received estrogen plus progestin compared with women in the placebo group.<h3>Conclusions</h3>Estrogen plus progestin was associated with greater breast cancer incidence, and the cancers are more commonly node-positive. Breast cancer mortality also appears to be increased with combined use of estrogen plus progestin.<h3>Trial Registration</h3>clinicaltrials.gov Identifier: NCT00000611
Active leflunomide metabolite inhibits interleukin 1beta, tumour necrosis factor alpha, nitric oxide, and metalloproteinase-3 production in activated human synovial tissue cultures
Authors: O Elkayam, I Yaron, I Shirazi, R Judovitch, D Caspi, M Yaron
Journal: Annals of the Rheumatic Diseases (2003)

Leflunomide is now an approved agent for the management of adult rheumatoid arthritis (RA). Its active metabolite A771726 inhibits de novo pyrimidine biosynthesis. Although considered to be an immunosuppressive agent, its mechanism of action remains obscure. Evaluation of the leflunomide active metabolite A771726 (LEF) effect on interleukin 1beta (IL1beta), tumour necrosis factor (TNFalpha), nitric oxide (NO), and stromelysin (metalloproteinase-3 (MMP-3)) production by activated human synovial tissue in culture. Synovial tissue was obtained during surgery from patients undergoing total knee replacement owing to RA or osteoarthritis (OA), cut into small pieces, and cultured in Petri dishes with test materials as previously described. IL1beta, TNFalpha, NO, and MMP-3 were measured in the culture media after 48 hours incubation with different doses of LEF by methods previously described. LEF (0.3, 3, and 9 micro g/ml) inhibited IL1beta production in the presence of lipopolysaccharide (LPS; 3 micro g/ml) in a dose dependent manner (p<0.01) at LEF 0.3 micro g/ml. TNFalpha production in the presence of IL1beta (1 ng/ml) was also inhibited in a dose dependent manner (p<0.05 at LEF 0.3 micro g/ml). NO and MMP-3 production in the presence of LPS (3 micro g/ml) was inhibited as well (p<0.01 at LEF 1 micro g/ml and at LEF 0.3 micro g/ml, respectively). Synovial cell viability evaluated by the tetrazolium salt XTT was unaffected by the LEF concentration used. There was no qualitative difference in the response of OA and RA synovial tissue. Leflunomide may modulate the rheumatoid articular process by inhibition of local production of IL1beta, TNFalpha, NO, and MMP-3.
Immunoglobulin Delta Expression in Burkitt's Lymphoma Cell Lines
Authors: J. Kiwanuka, G. Marti, J. Moore, M. Cheah, I. Magrath
Journal: JNCI Journal of the National Cancer Institute (1989)

Eighteen Burkitt's lymphoma (BL) cell lines were analyzed for rearrangement and expression of the delta gene. None had rearrangement of the delta gene locus within the 9.0-kb BamHI restriction fragment. Cell lines that expressed the delta gene contained both mu alleles, with at least one productively rearranged. Thirteen of 18 cell lines had detectable transcripts hybridizing with the delta probe. In 10 of the 13 cell lines with delta transcripts, cytoplasmic delta chains were detected, but only two of these expressed delta chains strongly on the surface. All 13 lines made cytoplasmic mu chains, and all except one made cytoplasmic light chains. Surface IgM was detected in all except two of the 13 cell lines. Although BL has generally been considered not to express IgD, except in occasional cases, previous studies have been confined to examination of the cell surface. Many of the cell lines that we examined express delta mRNA transcripts as well as produce cytoplasmic delta chains but no detectable surface IgD. This suggests that delta chains are detectable in the cytoplasm prior to being apparent on the surface. Our findings argue against an origin of BL from germinal center cells since IgD is almost totally lacking in normal B cells present in germinal centers. [J Natl Cancer Inst 81: 1075–1079, 1989]
TNRC9 Downregulates BRCA1 Expression and Promotes Breast Cancer Aggressiveness
Authors: Jingxuan Shan, Shoba P. DSouza, Sasha Bakhru, Eman K. Al-Azwani, Maria L. Ascierto, Konduru S. Sastry, Shahinaz Bedri, Dhanya Kizhakayil, Idil I. Aigha, Joel Malek, Issam Al-Bozom, Salah Gehani, Stacia Furtado, Edith Mathiowitz, Ena Wang, Francesco M. Marincola, Lotfi Chouchane
Journal: Cancer Research (2013)

Abstract Although the linkage between germline mutations of BRCA1 and hereditary breast/ovarian cancers is well established, recent evidence suggests that altered expression of wild-type BRCA1 might contribute to the sporadic forms of breast cancer. The breast cancer gene trinucleotide-repeat-containing 9 (TNRC9; TOX3) has been associated with disease susceptibility but its function is undetermined. Here, we report that TNRC9 is often amplified and overexpressed in breast cancer, particularly in advanced breast cancer. Gene amplification was associated with reduced disease-free and metastasis-free survival rates. Ectopic expression of TNRC9 increased breast cancer cell proliferation, migration, and survival after exposure to apoptotic stimuli. These phenotypes were associated with tumor progression in a mouse model of breast cancer. Gene expression profiling, protein analysis, and in silico assays of large datasets of breast and ovarian cancer samples suggested that TNRC9 and BRCA1 expression were inversely correlated. Notably, we found that TNRC9 bound to both the BRCA1 promoter and the cAMP-responsive element-binding protein (CREB) complex, a regulator of BRCA1 transcription. In support of this connection, expression of TNRC9 downregulated expression of BRCA1 by altering the methylation status of its promoter. Our studies unveil a function for TNRC9 in breast cancer that highlights a new paradigm in BRCA1 regulation. Cancer Res; 73(9); 2840–9. ©2013 AACR.
Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons
Authors: Liesbeth Reneman, Jan Booij, Kora de Bruin, Johannes B Reitsma, Frederik A de Wolff, W Boudewijn Gunning, Gerard J den Heeten, Wim van den Brink
Journal: The Lancet (2001)
Cardiac Hypertrophy in Rats with Phenylhydrazine Anemia
Authors: TOM D. NORMAN, ROBERT D. MCBROOM
Journal: Circulation Research (1958)

The effect of phenylhydrazine-produced anemia upon the hearts of rats was studied with observations upon the accompanying hypertrophy. Results indicated that the mechanism of hypertrophy under these conditions may be one of myocardial injury rather than mechanical.
Risk of colorectal cancer in juvenile polyposis
Authors: L. A A Brosens, A. van Hattem, L. M Hylind, C. Iacobuzio-Donahue, K. E Romans, J. Axilbund, M. Cruz-Correa, A. C Tersmette, G J. A Offerhaus, F. M Giardiello
Journal: Gut (2007)

Juvenile polyposis (JP) is an autosomal-dominant syndrome characterised by the development of hamartomatous gastrointestinal polyps and is associated with colorectal cancer. However, the relative and absolute risk of colorectal malignancy in these patients is not known.The incidence rates of colorectal cancer in patients with JP were compared with that of the general population through person-year analysis with adjustment for demographics.In patients with JP, the RR (95% CI) of colorectal cancer was 34.0 (14.4 to 65.7). Similar risks were noted in both males (30.0, 9.6 to 68.6) and females (43.7, 8.8 to 125). The cumulative life-time risk for colorectal cancer was 38.7%. The mean (SD) age of diagnosis of colorectal cancer was 43.9 (10.4) years. Other gastrointestinal malignancies were not noted in this cohort.Patients with JP have a markedly increased RR and absolute risk for colorectal cancer and require vigilant colorectal surveillance starting at young age. A low threshold for recommending surgery with consideration for removal of the entire colorectum seems warranted.
PERIOD OF INFECTIVITY OF PATIENTS WITH EXPERIMENTALLY INDUCED INFECTIOUS HEPATITIS
Authors: Walter P. Havens
Journal: The Journal of Experimental Medicine (1946)

1. Serum and stools obtained in the pre-icteric phase of one patient, and pooled specimens of the same materials from 5 patients with experimentally induced (by feeding) infectious hepatitis produced the disease in 10 out of 15 human volunteers following feeding or parenteral inoculation. 2. Pooled specimens of urine and nasopharyngeal washings from 5 patients, obtained in the acute phase of infectious hepatitis when virus was proven to be in the stool and serum, were not demonstrably infectious when fed and given intranasally to 6 volunteers. 3. Serum obtained in the midincubation period of one patient with experimentally induced infectious hepatitis failed to produce apparent infection when inoculated parenterally into 3 human volunteers. This is in contrast to the situation in homologous serum jaundice in which "virus" has been demonstrated in the sera of volunteers during the incubation period. 4. Serum and stools obtained from one patient and pooled specimens of stools from 5 patients 25 to 31 days after onset of experimental infectious hepatitis failed to produce apparent infection in 10 human volunteers. 5. No appreciable difference was detected in length of incubation period following the parenteral administration of widely different amounts of the same strain of "virus."
Increased Frequency and Suppression by Regulatory T Cells in Patients with Acute Myelogenous Leukemia
Authors: Miroslaw J. Szczepanski, Marta Szajnik, Malgorzata Czystowska, Magis Mandapathil, Laura Strauss, Ann Welsh, Kenneth A. Foon, Theresa L. Whiteside, Michael Boyiadzis
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Regulatory CD4+CD25highFoxp3+ T cells (Treg) control peripheral immune tolerance. Patients with cancer, including those with hematologic malignancies, have elevated numbers of Treg in the peripheral circulation and in tumor tissues. However, mechanisms of suppression and clinical significance of Treg, especially in patients with acute myelogenous leukemia (AML), has not been well defined. Experimental Design: We prospectively evaluated the phenotype, function, and mechanisms of suppression used by Treg in newly diagnosed untreated AML patients. The relationship between the frequency of circulating Treg and the disease status as well as treatment outcome was also evaluated. Results: The percentage of circulating Treg was higher (P &amp;lt; 0.0001) and their phenotype was distinct in AML patients relative to normal controls. Suppression mediated by Treg coincubated with proliferating autologous responder cells was also higher (P &amp;lt; 0.001) in AML than that mediated by control Treg. Using Transwell inserts, we showed that interleukin-10 and transforming growth factor-β1 production as well as cell-to-cell contact were necessary for Treg-mediated suppression. Also, the pretreatment Treg frequency predicted response to chemotherapy. Unexpectedly, patients who achieved complete remission still had elevated frequency of Treg, which mediated high levels of suppressor activity. Conclusions: Treg accumulating in the peripheral circulation of AML patients mediate vigorous suppression via contact-dependent and contact-independent mechanisms. Patients with lower Treg frequency at diagnosis have a better response to induction chemotherapy. During the post-induction period, the Treg frequency and suppressive activity remain elevated in complete remission, suggesting that Treg are resistant to conventional chemotherapy.
Characterization of CD4<sup>+</sup>CD25<sup>+</sup> Regulatory T Cells in Patients Treated With High-Dose Interleukin-2 for Metastatic Melanoma or Renal Cell Carcinoma
Authors: Giovanni C. Cesana, Gail DeRaffele, Seth Cohen, Dorota Moroziewicz, Josephine Mitcham, John Stoutenburg, Ken Cheung, Charles Hesdorffer, Seunghee Kim-Schulze, Howard L. Kaufman
Journal: Journal of Clinical Oncology (2006)

Purpose To characterize the number and functional status of CD4 + CD25 + regulatory T cells (Tregs) in patients with metastatic melanoma (MM) and renal cell carcinoma (RCC) treated with high-dose bolus interleukin-2 (IL-2). Patients and Methods Patients with MM or RCC treated with high-dose bolus IL-2 (600,000 IU/kg every 8 hours) at a single center provided pre- and post-treatment whole blood specimens. Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation, separated into cellular subsets, and analyzed by flow cytometry or used for in vitro proliferation assays. Results Between September 2003 and July 2005 57 patients were enrolled in the study with 48 patients available for analysis (45 MM, 12 RCC). Tregs were defined as CD4 + CD25 hi T cells, and this subset was significantly elevated in the cancer patients compared with normal donors (7.75% v 2.24%). The CD4 + CD25 hi T-cell pool in the patients constitutively expressed intracellular FoxP3, CTLA-4, and produced high amounts of IL-10. The Tregs were CCR7 + with 50% representing naïve and 50% central-memory T cells. The cells were functionally suppressive in mixed in vitro proliferation assays. Following IL-2 administration, the number and frequency of Tregs increased in patients with progressive disease but returned to normal levels in patients with objective clinical responses. Conclusion The number of Tregs, defined as CD4 + CD25 hi T cells is increased in patients with MM and RCC. High-dose IL-2 resulted in a significant decrease of Tregs in those patients achieving an objective clinical response to IL-2 therapy.
A BIOLOGICAL CLASSIFICATION OF ENCAPSULATUS PNEUMONIÆ (FRIEDLÄNDER'S BACILLUS)
Authors: Louis A. Julianelle
Journal: The Journal of Experimental Medicine (1926)

A biological classification has been made of thirty strains of Friedländer's bacillus. This study reveals that there exist among these strains three sharply defined and specific types and one heterogeneous group. The three types are Type A, fifteen strains; Type B, six strains; Type C, three strains; and Group X, six strains. The agglutination, agglutinin adsorption, protection, thread, and precipitin reactions have been employed in the working out of this classification, and the types have been proved highly specific by means of each serological test.
Entrapment neuropathy of the inferior branch of the suprascapular nerve by a ganglion cyst mimicking cervical disk disease
Authors: K Akgun
Journal: Annals of the Rheumatic Diseases (2003)

Paired two tailed Student's t test used to test differences between baseline and six month follow up values for both patient groups.ESR, erythrocyte sedimentation rate (normal value 5-15 mm/1st h); CRP, C reactive protein (normal value <10 mg/l); VAS, visual analogue score; BASFI, Bath Ankylosing Spondylitis Functional Index (0-100); BASDAI, Bath Ankylosing Spondylitis Disease Activity Index (0-100).
Gender, ethnicity and graduate status, and junior doctors’ self-reported preparedness for clinical practice: national questionnaire surveys
Authors: Elena Svirko, Trevor Lambert, Michael J Goldacre
Journal: Journal of the Royal Society of Medicine (2013)

Objectives Medical schools need to ensure that graduates feel well prepared for their first medical job. Our objective was to report on differences in junior doctors’ self-reported preparedness for work according to gender, ethnicity and graduate status. Design Postal and electronic questionnaires. Setting UK. Participants Medical graduates of 2008 and 2009, from all UK medical schools, one year after graduation. Main outcome measures The main outcome measure was the doctors’ level of agreement with the statement that ‘ My experience at medical school prepared me well for the jobs I have undertaken so far’, to which respondents were asked to reply on a scale from ‘ strongly agree’ to ‘ strongly disagree’. Results Women were slightly less likely than men to agree that they felt well prepared for work (50% of women agreed or strongly agreed vs. 54% of men), independently of medical school, ethnicity, graduate entry status and intercalated degree status, although they were no more likely than men to regard lack of preparedness as having been a problem for them. Adjusting for the other subgroup differences, non-white respondents were less likely to report feeling well prepared than white (44% vs. 54%), and were more likely to indicate that lack of preparedness was a problem (30% non-white vs. 24% white). There were also some gender and ethnic differences in preparedness for specific areas of work. Conclusions The identified gender and ethnic differences need to be further explored to determine whether they are due to differences in self-confidence or in actual preparedness.
Diabetes Contributes to Cholesterol Metabolism Regardless of Obesity
Authors: Piia P. Simonen, Helena K. Gylling, Tatu A. Miettinen
Journal: Diabetes Care (2002)

OBJECTIVE—To investigate cholesterol metabolism in obesity with and without diabetes. RESEARCH DESIGN AND METHODS—We performed cross-sectional metabolic studies in obese individuals with and without type 2 diabetes. The study population consisted of 16 obese (BMI &amp;gt;30 kg/m2) diabetic subjects with a mean age of 52 ± 2 years (SE) and 16 nondiabetic control subjects of similar age and weight. Cholesterol absorption efficiency was measured with peroral dual isotopes and cholesterol synthesis with sterol balance. RESULTS—Serum total cholesterol did not differ between the groups, but LDL and HDL cholesterol were significantly lower and VLDL cholesterol and serum total and VLDL triglycerides were higher in the diabetic group than in the control group. Cholesterol absorption efficiency was 29 ± 1% in diabetic subjects vs. 42 ± 2% in the control subjects (P &amp;lt; 0.01). Cholesterol synthesis was higher (17 ± 1 vs. 14 ± 1 mg · kg−1 · day−1; P &amp;lt; 0.05) and neutral sterol and bile acid excretion and cholesterol turnover tended to be higher in the diabetic group than in the control group. Blood glucose was positively related to cholesterol synthesis in the diabetic group (r = +0.663, P &amp;lt; 0.01) and in the control group (r = +0.590, P &amp;lt; 0.05), suggesting that the higher blood glucose level, the higher the cholesterol synthesis. In addition, blood glucose was significantly positively related to fecal neutral sterol excretion in both groups. CONCLUSIONS—Cholesterol absorption efficiency was lower and cholesterol synthesis was higher in obese subjects with diabetes than in those without diabetes, suggesting that diabetes modulates cholesterol metabolism more than obesity alone.
Screening for Lung Cancer: U.S. Preventive Services Task Force Recommendation Statement
Authors: Virginia A. Moyer
Journal: Annals of Internal Medicine (2013)

Description: Update of the 2004 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for lung cancer. Methods: The USPSTF reviewed the evidence on the efficacy of low-dose computed tomography, chest radiography, and sputum cytologic evaluation for lung cancer screening in asymptomatic persons who are at average or high risk for lung cancer (current or former smokers) and the benefits and harms of these screening tests and of surgical resection of early-stage non–small cell lung cancer. The USPSTF also commissioned modeling studies to provide information about the optimum age at which to begin and end screening, the optimum screening interval, and the relative benefits and harms of different screening strategies. Population: This recommendation applies to asymptomatic adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Recommendation: The USPSTF recommends annual screening for lung cancer with low-dose computed tomography in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation)