tbuckley/cabot-search huggingface dataset:
Homing In on Mechanisms Linking Breast Density to Breast Cancer Risk
Authors: Vicki Brower
Journal: JNCI Journal of the National Cancer Institute (2010)

I n probably the best-known finding from the Women’s Health Initiative, postmenopausal hormone therapy with estrogen and progestin was linked to a substantial increase in breast cancer risk. Now researchers think that the increase may be explained by an associated rise in breast density. Among women taking hormone therapy in the large, prospective women’s health study, both the density found on baseline mammograms and the change in density were statistically signifi cantly associated with breast cancer risk, according to Celia Byrne, Ph.D., assistant professor at Georgetown University’s Lombardi Comprehensive Cancer Center. Byrne discussed the results of this new analysis of Women’s Health Initiative data at the 2010 American Association of Cancer Research meeting in April. Researchers now consider mammographic density — the amount of white, radiodense area compared with the amount of gray, radiolucent area on a mammogram — one of the strongest independent risk factors for breast cancer ( see “Breast Density Gains Acceptance as Breast Cancer Risk Factor,” J. Natl. Cancer Inst. 2010;102:374 – 5). But researchers do not fully understand just how breast density increases breast cancer risk. Research into the biological mechanisms underlying breast density and linking it to breast cancer risk has been an understudied area, according to Paolo Provenzano, Ph.D. , a research associate at Seattle’s Fred Hutchinson Cancer Research Center. That situation is changing as Provenzano and others have begun to identify some of the complex biological processes that account for breast density and to explain how they affect breast tissue. “Direct studies to begin to address a causal relationship between breast tissue density and cancer have only started to emerge,” Provenzano said. “While there is still much work to be done, I believe that high breast tissue density is causal for the increasing risk of developing breast cancer.”
Existing classes of antibiotics are probably the best we will ever have
Authors: M. Cormican, A. Vellinga
Journal: BMJ (2012)

Paccaud emphasises economic incentives for new antibiotic discovery to tackle antibiotic resistance.1 An ecological perspective suggests that new drug discovery may not make a major contribution.

The ideal target for antibiotic action is a crucial step in bacterial physiology with no parallel in mammalian cells—for example, penicillin targets a step in cell wall synthesis. Because there …
In vivo selection of MGMT(P140K) lentivirus–transduced human NOD/SCID repopulating cells without pretransplant irradiation conditioning
Authors: Steven P. Zielske, Jane S. Reese, Karen T. Lingas, Jon R. Donze, Stanton L. Gerson
Journal: Journal of Clinical Investigation (2003)

Infusion of transduced hematopoietic stem cells into nonmyeloablated hosts results in ineffective in vivo levels of transduced cells. To increase the proportion of transduced cells in vivo, selection based on P140K O6-methylguanine-DNA-methyltransferase (MGMT[P140K]) gene transduction and O6-benzylguanine/1,3-bis(2-chloroethyl)-1-nitrosourea (BG/BCNU) treatment has been devised. In this study, we transduced human NOD/SCID repopulating cells (SRCs) with MGMT(P140K) using a lentiviral vector and infused them into BG/BCNU–conditioned NOD/SCID mice before rounds of BG/BCNU treatment as a model for in vivo selection. Engraftment was not observed until the second round of BG/BCNU treatment, at which time human cells emerged to compose up to 20% of the bone marrow. Furthermore, 99% of human CFCs derived from NOD/SCID mice were positive for provirus as measured by PCR, compared with 35% before transplant and 11% in untreated irradiation-preconditioned mice, demonstrating selection. Bone marrow showed BG-resistant O6-alkylguanine-DNA-alkyltransferase (AGT) activity, and CFUs were stained intensely for AGT protein, indicating high transgene expression. Real-time PCR estimates of the number of proviral insertions in individual CFUs ranged from 3 to 22. Selection resulted in expansion of one or more SRC clones containing similar numbers of proviral copies per mouse. To our knowledge, these results provide the first evidence of potent in vivo selection of MGMT(P140K) lentivirus–transduced human SRCs following BG/BCNU treatment.
Multiple forms of epileptic attack secondary to a small chronic subdural haematoma.
Authors: S. C. Jones, J. M. Bamford, J. Heath, N. Bradey, R. V. Heatley
Journal: BMJ (1989)

Une observation rare: malade de 75 ans presentant un petit hematome sous-dural dans la region fronto-temporale gauche;. Les seules manifestations cliniques sont des crises epileptiques variees: convulsions, absences, confusion mentale etc.
1257 IS LIVER CIRRHOSIS ASSOCIATED WITH INCREASED SUSCEPTIBILITY TO INFECTION BY HEPATITIS E VIRUS?
Authors: R. Jardí, D. Tabernero, M. Horns, F. Rodríguez-Frias, L. Castells, I. Campos-Varela, A. Caballero, M.C. Cantarell, R. Girones, R. Esteban, M. Buti
Journal: Journal of Hepatology (2011)
How to Reduce Mortality in Hemodialysis Patients Still a Puzzle
Authors: Mike Mitka
Journal: JAMA (2002)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
CD22 Is Both a Positive and Negative Regulator of B Lymphocyte Antigen Receptor Signal Transduction: Altered Signaling in CD22-Deficient Mice
Authors: Shinichi Sato, Ann S. Miller, Makoto Inaoki, Cheryl B. Bock, Paul J. Jansen, Mimi L.K. Tang, Thomas F. Tedder
Journal: Immunity (1996)
Screening for Chlamydia trachomatis: a case for empirical treatment
Authors: R. A. Gunn
Journal: JAMA (1994)

To the Editor.  —The article by Dr Shafer and colleagues 1 regarding urine-based screening strategies to detect Chlamydia trachomatis infection among sexually active asymptomatic young men provided valuable information. As part of a Chlamydia Prevention Initiative in San Diego County, California, we advocate that sexually active asymptomatic adolescent males be screened during routine preventive health care visits, such as during sports physicals. We recommend first-void urine leukocyte esterase (LE) testing because it can be done in the physician's office at negligible cost (approximately 30 cents). For adolescents with a positive LE, especially those engaging in high-risk sexual behavior, we recommend strong consideration of empirical treatment, and for others, further evaluation and confirmatory testing.  Confirmatory testing may not be available in certain settings, mainly because of cost concerns, and even when it can be done, some adolescents may not return to obtain results or treatment. Therefore, there is a need for a
Contralateral Prophylactic Mastectomy
Authors: Shoshana M. Rosenberg, Ann H. Partridge
Journal: JAMA Surgery (2014)

Most women who have contralateral prophylactic mastectomy (CPM) do not have clear clinical indications for undergoing the procedure, fueling concerns about overuse, as highlighted in the article by Hawley and colleagues.1 Focusing on improving informed decision-making is one starting point. However, breast cancer surgical decisions are made at an emotional time when fully understanding and weighing the true risks (e.g., surgical complications, self-image, and sexual effects) and benefits (e.g. reduced risk of contralateral cancer) associated with CPM might be difficult for some patients. Anxiety and fear certainly hamper optimal decision-making,2,3 and greater psychological and emotional support may prove invaluable in this setting. Further complicating informed decision-making is the tendency for people to not believe that risk estimates apply to them personally.4

An underlying tension exists between “do no harm,” viewing CPM as medically unnecessary given the lack of demonstrated benefit on recurrence and survival, and respect for patient preferences and autonomy. While CPM might be considered over-treating women without clinical indications, it might still be the right choice for some women for risk reduction, cosmetic and/or emotional reasons. The Institute of Medicine5 recently categorized shared decision making in the context of cancer care as “suboptimal”, underscoring a need for better patient-clinician communication. Decision-making surrounding early breast cancer, with respect to CPM in particular, provides an opportunity to encourage a supportive, shared, decision-making approach. Not only should pros and cons of different treatment options be communicated, but there needs to be consideration of the patient's personal circumstances and perceptions, all the while addressing anxiety and concerns about breast cancer recurrence and new primary disease (and the distinction between the two). Finding balance around this issue, like the decision process itself, should be a goal shared by patients and clinicians alike.
Gait analysis in ankylosing spondylitis.
Authors: L Zebouni, P S Helliwell, A Howe, V Wright
Journal: Annals of the Rheumatic Diseases (1992)

A study was conducted to compare the gait pattern of 12 patients with ankylosing spondylitis with axial disease only with that of 11 healthy controls using a telemeterised electrogoniometer gait analysis system. The reproducibility of the gait variables was found to be acceptable. Angles for movement at the hip and knee were less in patients with ankylosing spondylitis, but hip/knee angle ratios did not differ between the two groups. The stride length was shorter in the patients with ankylosing spondylitis. These findings are due to the increased rigidity of the spine, which results in decreased shock absorption and consequently a more cautious gait pattern in the absence of clinically and radiologically detectable peripheral joint disease.
Abstract 2865: Gemcitabine causes telomere shortening by stabilizing TRF2
Authors: Su Chih-Hao, Tsai Ying-Chieh, Lee Wei-Ping
Journal: Cancer Research (2012)

Abstract Gemcitabine is an effective anti-cancer agent against sold tumors. The pharmacological mechanism of gemcitabine is known as incorporation into DNA and thereby inhibition of DNA synthesis. Here, we report that gemcitabine treatment not only induced growth arrest and apoptosis in HeLa cells, but also caused telomere shortening without affecting telomerase activity. We performed cycloheximide chase assay to confirm that the half-life of TRF2, a telomere regulator, was prolonged in a dose-pendent manner under the treatment of gemcitabine. In addition, we did in vivo ubiquitination assay and found gemcitabine treatment increased TRF2 protein level by reducing the amount of ubiquitinated TRF2. And, the results of subcellular fractionation and immunostaining showed that the accumulated TRF2 indeed translocates into nucleus. Since TRF2 is a telomeric DNA binding protein, we then made an attempt to determine whether the accumulated TRF2 binds on telomeric DNA. We did chromatin immunoprecipitation and the result revealed that the accumulated TRF2 not only translocates into nucleus but also binds to telomeric DNA. Previous study has shown that XPF-ERCC1, a structure-specific endonuclease and negative mediator of telomere length, interacts with TRF2, also required for TRF2-promoting telomere shortening. To confirm this interaction also exists in HeLa cells under the treatment of gemcitabine, we carried out immunoprecipitation with anti-TRF2 and anti-XPF antibodies and a de-telomeric DNA pull-down assay. Consistently, the results of both assay indicated that increased nuclear TRF2 which was induced by gemcitabine treatment is capable of recruiting more XPF/ERCC1 complex onto telomeric DNA. Besides, the binding studies by experimental manipulation of TRF2 confirmed that the binding ability of XPF-ERCC1 to telomere closely relates to TRF2 and resulted in telomere shortening. Together, these results show that gemcitabine enhances the nuclear accumulation of TRF2 and increased the amount of DNA-bound TRF2, therefore recruiting more XPF/ERCC1 to telomeric DNA and strengthening the nuclease activity of XPF, and resulting in telomere shortening. Since telomere loss is closely related to occurrence of apoptosis, gemcitabine may exert its anti-cancer effect by inducing TRF2 and telomere shortening. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2865. doi:1538-7445.AM2012-2865
Treatment of E2E2 homozygous familial dysbetalipoproteinemic subjects with gemfibrozil does not enhance the binding of their d &lt; 1.019 lipoprotein fraction to the low-density lipoprotein receptor
Authors: Monique Mulder, Augustinus H.M. Smelt, Shui P. Zhao, Rune R. Frants, Louis M. Havekes
Journal: Metabolism (1993)
THE COMPLEMENT-FIXATION TEST IN SYPHILIS
Authors: C.H. BROWNING, E.L. KENNAWAY
Journal: British Journal of Dermatology (1919)

IT is axiomatic that the clinical diagnosis of a disease can onl}-be regarded as satisfactory in tlie statistical sense when certain conditions are strictly fulfilled as to the constancy of the signs and symptoms in tlie condition and their uniform absence in other diseases.In the case of the infections it is becoming more and more widely recognised that it is necessary always to be on the look-out for atypical manifestations-tliatis to say, one must not be satisfied with any given symptom-complex as a diagnostic feature.It is true that many infections produce remarkably characteristic pictures, and tho skin-eruptions of syphilis, smallpox or measles at once suggest themselves as striking examples.The degree of diagnostic acumen which enabled typical cases of such diseases to be accurately differentiated was attained long ago by competent observers.It is certain, however, that the recognition of typical cases touches only the fringe of the question of infective disease, especially in connection with prevention.The essential problem which demands solution iswhat relationship exists between the number of the typical cases and of those which cannot be recognised with certainty by ordinary clinical methods.Where the proportion of clinically dubious manifestations is considerable the result is failure to deal effectively with the condition by administrative methods, such as isolation.This is VOL.xxxr.L
Production of Vitamin B12 Analogues in Patients with Small-Bowel Bacterial Overgrowth
Authors: L J Brandt, L H Bernstein, A Wagle
Journal: Annals of Internal Medicine (1977)

We investigated the presence of vitamin B12 analogues (cobamides) and the bacterial conversion of 57Co-B12 (vitamin B12 cyanocobalamin, [57Co]-CN-Cbl) into cobamides in the intestinal contents of four patients with bacterial overgrowth. The (57Co)-CN-Cbl bound to intrinsic factor was given orally. Jejunal contents were aspirated for 24 h and cultured aerobically and anaerobically. The CN-Cbl and cobamides were separated by electrophoresis and chromatography and identified by bioautography. Radioactivity of cobamide zones from duplicate chromatograms showed bacterial conversion of (57Co)-CN-Cbl into cobamides. Cobamides ([AdeJCNCba, [2-Me Ade] CNCba, [CN]2Cbi and factor E) were found in the intestinal contents in three of the four patients, and in two of three patients cobamides represented more than 25% of the administered CN-Cbl. Thus bacterial production of cobamides, both de novo and from ingested CN-Cbl bound to intrinsic factor, occurs in humans with bacterial overgrowth states and results in a significant loss of vitamin B12 to the host.
Dosing Schedules of 6-Month Regimens and Relapse for Pulmonary Tuberculosis
Authors: Kwok C. Chang, Chi C. Leung, Wing W. Yew, Shiu L. Chan, Cheuk M. Tam
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

The optimal approach for reducing tuberculosis relapse is open.We examined the possibility of reducing relapse by increasing dosing schedules.We conducted a systematic review of published clinical trials involving adult cohorts with pulmonary tuberculosis treated using 6-mo rifamycin-containing regimens, which were grouped under seven categories ordered by dosing schedules. Assuming cavitation and positive 2-mo culture were the driving forces for relapse, a static deterministic model apportioned observed numbers with and without relapse in each cohort into eight subgroups. Combining subgroups stratified by cavitation, 2-mo culture, and regimens enabled estimation of adjusted relapse risks. chi2 Tests for trend and logistic regression analysis examined the relationship between relapse and dosing schedules.We identified 200 cases of bacteriologic relapse out of 5,208 patients in 32 cohorts. A logistic risk model showed a significant dose-response relationship between dosing schedules and relapse, with the following odds (95% confidence intervals) of relapse relative to daily regimens: 1.6 (0.6-4.1) for daily initial phase (IP) plus thrice-weekly continuation phase (CP), 2.8 (1.3-6.1) for daily IP plus twice-weekly CP, 2.8 (1.4-5.7) for thrice-weekly, 5.0 (2.4-10.5) for daily IP plus once-weekly rifapentine, and 7.1 (3.3-15.3) for thrice-weekly IP plus once-weekly rifapentine. In the presence of cavitation, only 6-mo daily or daily IP plus thrice-weekly CP attained best-estimated relapse risks below 5%; they reached 6% when 2-mo culture was also positive.Cavitary tuberculosis is best treated with 6-mo regimens comprising daily IP and thrice-weekly CP, which may be extended when 2-mo culture is positive.
Types of human papillomavirus isolated from Japanese patients with epidermodysplasia verruciformis
Authors: R. KANDA, T. TANIGAKI, Y. KITANO, K. YOSHIKAWA, M. YUTSUDO, A. HAKURA
Journal: British Journal of Dermatology (1989)

Virological studies were performed on 12 patients with epidermodysplasia verruciformis (EV). Three types of lesions were observed: red plaques, pityriasis versicolor (PV)-like macules and plane warts. Human papillomavirus (HPV) 14, 20 and 21 were isolated from the plaques, HPV 3, 14 and 38 from flat warts and HPV 5, 12, 17, 20 and 38 from PV-like lesions. No clear relationship could be established between the different lesions and the types of HPV. Types 17 and 20 have been isolated most frequently from Japanese EV patients and HPV 5, frequently detected in other countries, is less common, whereas HPV 8 has not been isolated. Skin cancers occurred in six of the cases (50%) and all had benign lesions that were PV-like. At least one type of HPV 5, 17 or 20 could be isolated from these benign lesions and HPV 17 or 20 detected in the cancers. These three types of HPV in EV patients appear to be involved in the malignant transformation.
Human leukocyte antigen polymorphisms in italian primary biliary cirrhosis: A multicenter study of 664 patients and 1992 healthy controls
Authors: Pietro Invernizzi, Carlo Selmi, Francesca Poli, Sara Frison, Annarosa Floreani, Domenico Alvaro, Piero Almasio, Floriano Rosina, Marco Marzioni, Luca Fabris, Luigi Muratori, Lihong Qi, Michael F. Seldin, Eric M. Gershwin, Mauro Podda
Journal: Hepatology (2008)

Abstract Genetic factors are critical in determining susceptibility to primary biliary cirrhosis (PBC), but there has not been a clear association with human leukocyte antigen (HLA) genes. We performed a multicenter case-control study and analyzed HLA class II DRB1 associations using a large cohort of 664 well-defined cases of PBC and 1992 controls of Italian ancestry. Importantly, healthy controls were rigorously matched not only by age and sex, but also for the geographical origin of the proband four grandparents (Northern, Central, and Southern Italy). After correction for multiple testing, DRB1*08 [odds ratio (OR), 3.3; 95% confidence interval (CI), 2.4-4.5] and DRB1*02 (OR 0.9; 95% CI 0.8-1.2) were significantly associated with PBC, whereas alleles DRB1*11 (OR 0.4; 95% CI 0.3-0.4) and DRB1*13 (OR 0.7; 95% CI 0.6-0.9) were protective. When subjects were stratified according to their grandparental geographical origin, only the associations with DRB1*08 and DRB1*11 were common to all three areas. Associated DRB1 alleles were found only in a minority of patients, whereas an additive genetic model is supported by the gene dosage effect for DRB1*11 allele and the interaction of DRB1*11,*13, and *08. Lastly, no significant associations were detected between specific DRB1 alleles and relevant clinical features represented by the presence of cirrhosis or serum autoantibodies. In conclusion, we confirm the role for HLA to determine PBC susceptibility and suggest that the effect of HLA is limited to patient subgroups. We suggest that a large whole-genome approach is required to identify further genetic elements contributing to the loss of tolerance in this disease. (Hepatology 2008;48:1906-1912.)
Walnut-enriched diet reduces fasting non-HDL-cholesterol and apolipoprotein B in healthy Caucasian subjects: A randomized controlled cross-over clinical trial
Authors: Liya Wu, Katja Piotrowski, Tiina Rau, Elisa Waldmann, Uli C. Broedl, Hans Demmelmair, Berthold Koletzko, Renee G. Stark, Jutta M. Nagel, Christos S. Mantzoros, Klaus G. Parhofer
Journal: Metabolism (2013)

Walnut consumption is associated with reduced risk of coronary heart disease (CHD).We assessed the effect of walnuts on lipid and glucose metabolism, adipokines, inflammation and endothelial function in healthy Caucasian men and postmenopausal women ≥50years old.Forty subjects (mean±SEM: age 60±1years, BMI 24.9±0.6kg/m(2); 30 females) were included in a controlled, cross-over study and randomized to receive first a walnut-enriched (43g/d) and then a Western-type (control) diet or vice-versa, with each lasting 8weeks and separated by a 2-week wash-out. At the beginning and end of each diet phase, measurements of fasting values, a mixed meal test and an assessment of postprandial endothelial function (determination of microcirculation by peripheral artery tonometry) were conducted. Area under the curve (AUC), incremental AUC (iAUC) and treatment×time interaction (shape of the curve) were evaluated for postprandial triglycerides, VLDL-triglycerides, chylomicron-triglycerides, glucose and insulin.Compared with the control diet, the walnut diet significantly reduced non-HDL-cholesterol (walnut vs. control: -10±3 vs. -3±2mg/dL; p=0.025) and apolipoprotein-B (-5.0±1.3 vs. -0.2±1.1mg/dL; p=0.009) after adjusting for age, gender, BMI and diet sequence. Total cholesterol showed a trend toward reduction (p=0.073). Fasting VLDL-cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and glucose, insulin, HOMA-IR, and HbA1c did not change significantly. Similarly, fasting adipokines, C-reactive protein, biomarkers of endothelial dysfunction, postprandial lipid and glucose metabolism and endothelial function were unaffected.Daily consumption of 43g of walnuts for 8weeks significantly reduced non-HDL-cholesterol and apolipoprotein-B, which may explain in part the epidemiological observation that regular walnut consumption decreases CHD risk.