tbuckley/cabot-search huggingface dataset:
Hematopoietic stem cell regulatory volumes as revealed in studies of the bgj/bgj:W/WV chimera.
Authors: M A Maloney, M J Dorie, R A Lamela, Z R Rogers, H M Patt
Journal: The Journal of Experimental Medicine (1978)

The kinetics of bone marrow replacement was studied in W/WV mice implanted with gbj/bgj (beige) stem cells, with the characteristic beige neutrophil marker as a criterion of the takeover of host marrow by donor marrow. A hyperbolic pattern of W/WV marrow replacement conforming to a log dose-response was observed in experiments encompassing a 50-fold range of bgj/bgj inoculum doses and a 2-yr period of observation. The dose-response relationships were consistent with random seeding of stem cells in the host marrow coupled with a decreasing efficiency of secondary colonization by local migration. Application of single-hit Poisson sampling statistics to the dose-response data led to the hypothesis that mouse bone marrow is compartmentalized into essentially self-contained stem cell regulatory volumes or domains. We estimate that W/WV marrow contains about 2,600 stem cells regulatory units with an average volume of about 10(8) micron3, a dimension consistent with the presumptive role of short-range cell-cell interactions in the regulation of pluripotent stem cells. Our analysis of the dose-response data is also indicative of the discontinuous and limited nature of local stem cell migration in a cellular marrow, a consideration that may be of practical as well as theoretical interest.
Cardiorespiratory Fitness and Classification of Risk of Cardiovascular Disease Mortality
Authors: Sachin Gupta, Anand Rohatgi, Colby R. Ayers, Benjamin L. Willis, William L. Haskell, Amit Khera, Mark H. Drazner, James A. de Lemos, Jarett D. Berry
Journal: Circulation (2011)

Background— Cardiorespiratory fitness (fitness) is associated with cardiovascular disease (CVD) mortality. However, the extent to which fitness improves risk classification when added to traditional risk factors is unclear. Methods and Results— Fitness was measured by the Balke protocol in 66 371 subjects without prior CVD enrolled in the Cooper Center Longitudinal Study between 1970 and 2006; follow-up was extended through 2006. Cox proportional hazards models were used to estimate the risk of CVD mortality with a traditional risk factor model (age, sex, systolic blood pressure, diabetes mellitus, total cholesterol, and smoking) with and without the addition of fitness. The net reclassification improvement and integrated discrimination improvement were calculated at 10 and 25 years. Ten-year risk estimates for CVD mortality were categorized as &lt;1%, 1% to &lt;5%, and ≥5%, and 25-year risk estimates were categorized as &lt;8%, 8% to 30%, and ≥30%. During a median follow-up period of 16 years, there were 1621 CVD deaths. The addition of fitness to the traditional risk factor model resulted in reclassification of 10.7% of the men, with significant net reclassification improvement at both 10 years (net reclassification improvement=0.121) and 25 years (net reclassification improvement=0.041) ( P &lt;0.001 for both). The integrated discrimination improvement was 0.010 at 10 years ( P &lt;0.001), and the relative integrated discrimination improvement was 29%. Similar findings were observed for women at 25 years. Conclusions— A single measurement of fitness significantly improves classification of both short-term (10-year) and long-term (25-year) risk for CVD mortality when added to traditional risk factors.
Abstract P2-12-09: Developing clinical sequencing assays at Einstein-Montefiore
Authors: M Delio, K Patel, A Maslov, A Golden, J Greally, B Morrow, J Vijg, C Montagna
Journal: Cancer Research (2013)

Abstract The Department of Genetics in collaboration with a group of Montefiore's clinicians initiated the development of clinical sequencing tests with the final goal to incrementally build clinical sequencing assays to improve clinical care in the Bronx. The use of next generation sequencing is particularly relevant for cancer biology since the heterogeneity of cancer requires deep sequencing and high read depth, which prior to recent advances in technology was expensive and labor intensive. We designed a custom gene panel for target sequencing using the Illumina HiSeq 2500 consisting of 650 genes for multiple disorders and diseases, including various cancers, in addition to rare and complex mendelian disorders. We sequenced 17 samples, including a tumor-normal breast cancer pair, where we identified a novel, pathogenic stop variant in the highly mutated TP53 tumor suppressor gene. In addition to our custom target panel, we sequenced this sample pair on two additional cancer panels (AmpliSeq Cancer Hotspot and the Comprehensive Cancer Panel using the Ion Torrent Technology) and performed Whole Exome Sequencing (WES) to ensure the sensitivity and specificity of our custom panel. This variant was detected on all platforms. We found targeted capture high-throughput sequencing to be a cost effective, time sensitive and efficient approach in detecting pathogenic variants to aid diagnosis of individuals affected by cancer or mendelian disorders. We are currently receiving samples to sequence and plan to expand our program to various groups within the Einstein-Montefiore community. Using a personalized medicine approach we expect to detect biomarkers and prospective targets to develop an accurate and effective treatment plan for these individuals. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-12-09.
Myelodysplastic syndrome after acute promyelocytic leukemia: the European APL group experience
Authors: I Lobe, F Rigal-Huguet, A Vekhoff, B Desablens, D Bordessoule, C Mounier, A Ferrant, M Sanz, M Fey, C Chomienne, S Chevret, L Degos, P Fenaux
Journal: Leukemia (2003)
Reduction in Infarct Size, Arrhythmias, Chest Pain and Morbidity by Early Intravenous β-Blockade in Suspected Acute Myocardial Infarction
Authors: S. Yusuf, P. Rossi, D. Ramsdale, R. Peto, L. Furse, R. Motwani, S. Parish, R. Gray, D. Bennett, C. Bray, P. Sleight
Journal: Drugs (1983)
Capsule endoscopy diagnosis of radiation enteritis in a patient previously considered to have celiac sprue
Authors: A. Jazwinski, J. Palazzo, D. Kastenberg
Journal: Endoscopy (2007)

A 65-year-old woman, who had been diagnosed with celiac sprue, presented with chronic diarrhea, fatigue, anorexia, and impaired night vision despite following a strict gluten-free diet. Diarrhea began 10 years earlier, around the time she underwent hysterectomy followed by pelvic radiation for endometrial cancer. Five years later, celiac sprue was diagnosed based on a positive gliadin IgG antibody and small-bowel biopsies revealing villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes.
Hepatocyte nuclear factor-4α reverses malignancy of hepatocellular carcinoma through regulating miR-134 in the DLK1-DIO3 region
Authors: Chuan Yin, Pei-Qin Wang, Wen-Ping Xu, Yuan Yang, Qing Zhang, Bei-Fang Ning, Ping-Ping Zhang, Wei-Ping Zhou, Wei-Fen Xie, Wan-Sheng Chen, Xin Zhang
Journal: Hepatology (2013)

Hepatocyte nuclear factor-4α (HNF4α) is a dominant transcriptional regulator of hepatocyte differentiation and hepatocellular carcinogenesis. There is striking suppression of hepatocellular carcinoma (HCC) by HNF4α, although the mechanisms by which HNF4α reverses HCC malignancy are largely unknown. Herein, we demonstrate that HNF4α administration to HCC cells resulted in elevated levels of 28 mature microRNAs (miRNAs) from the miR-379-656 cluster, which is located in the delta-like 1 homolog (DLK1) -iodothyronine deiodinase 3 (DIO3) locus on human chromosome 14q32. Consistent with the reduction of HNF4α, these miRNAs were down-regulated in human HCC tissue. HNF4α regulated the transcription of the miR-379-656 cluster by directly binding to its response element in the DLK1-DIO3 region. Interestingly, several miRNAs in this cluster inhibited proliferation and metastasis of HCC cells in vitro. As a representative miRNA in this cluster, miR-134 exerted a dramatically suppressive effect on HCC malignancy by down-regulating the oncoprotein, KRAS. Moreover, miR-134 markedly diminished HCC tumorigenicity and displayed a significant antitumor effect in vivo. In addition, inhibition of endogenous miR-134 partially reversed the suppressive effects of HNF4α on KRAS expression and HCC malignancy. Furthermore, a positive correlation between HNF4α and miR-134 levels was observed during hepatocarcinogenesis in rats, and decreases in miR-134 levels were significantly associated with the aggressive behavior of human HCCs. Conclusion: Our data highlight the importance of the miR-379-656 cluster in the inhibitory effect of HNF4α on HCC, and suggest that regulation of the HNF4α-miRNA cascade may have beneficial effects in the treatment of HCC. (Hepatology 2013; 58:1964–1976)
Liaison Officers for Hospital Junior Doctors
Authors: R. E. W. Oliver
Journal: BMJ (1970)

Twenty-eight years agol I descrbed experiments in which I self-administered 1-2 mg. of nicotine hypodermically three or four times a day, with some smoking, for a month.I actually took over 150 doses by various routes.After a month I preferred a hypodermic of nicotine to a cigarette in- haled.I also found that 0.1 mg. of nicotine intravenously had exactly the same subjective action as one deep inhalation of cigarette smoke.Clearly therefore smoking is essentially a means of taking doses of nicotine and is governed not by a psychophysiological, but by a (psycho-)pharnfa- cological mechanism or, in simple language, by recurrent craving for tobacco.-Iam, etc.,
Semper Fidelis — Consumer Protection for Patients with Implanted Medical Devices
Authors: William H. Maisel
Journal: New England Journal of Medicine (2008)

When the Food and Drug Administration (FDA) approved the Medtronic Sprint Fidelis implantable cardioverter–defibrillator (ICD) lead in 2004 on the basis of bench testing but no human clinical data, there was no public outcry. Physicians rapidly incorporated the new electrode into their practice, welcoming its small diameter and ease of implantation. During the ensuing 3 years, 90% of Medtronic ICDs were implanted with this lead (see diagram). But in October 2007, after 38 months on the U.S. market and 268,000 implantations worldwide, the Fidelis was voluntarily recalled by Medtronic because of its propensity to fracture. The large number of affected . . .
Abstract 3002: Long Term Oral Contraceptive Use is an Independent Risk Factor for Arterial Stiffening
Authors: Ernst Rietzschel, Marc De Buyzere, Patrick Segers, Sofie Bekaert, Dirk De Bacquer, Guy De Backer, Thierry Gillebert
Journal: Circulation (2008)

Oral contraceptives (OC) are among the most frequently used drugs in the world with approximately 100 million women worldwide taking OC. In contrast to the active controversy surrounding hormone replacement therapy, little attention has been focused on OC, a drug therapy taken by far more women for far longer time periods. We describe the population effects of current and long-term OC exposure on a prognostically well validated marker of arterial stiffness: carotid-femoral pulse wave velocity (PWV). The Asklepios study is a representative sample (2524 apparently healthy M/F volunteers, aged 35–55 years, 1301 women) from the Belgian general population, free from overt cardiovascular disease. The subjects were extensively screened (biochemistry, lifestyle, cardiac and vascular echography, arterial tonometry). PWV was measured from flow patterns registered by Doppler echography in the femoral and carotid arteries. Of 1301 women (median age 45.7 y), 27.4% were actively taking OC. In contrast past use of OC is far more prevalent with 81% of women having taken OC for at least 1 year. The median duration of exposition in these women was 13 years. Age-adjusted PWV was higher in women currently taking OC: 6.75 versus 6.55 m/s (difference 0.19 ± 0.09 m/s; p = 0.034). However, current OC users also had higher blood pressures (BP): systolic BP (+4.4 ± 0.9 mmHg; p &lt; 0.001), diastolic BP (+2.3 ± 0.6 mmHg; p &lt; 0.001). After adjustement for BP, the difference in PWV between current OC users and non-users became non-significant: 6.60 versus 6.62 m/s (difference 0.02 ± 0.09 m/s; p = 0.814). In contrast, duration of OC use is a significant determinant of PWV, even after adjustement for age, BP, lipid levels, body size, heart rate, drug therapy (lipid-lowering, antihypertensive), glycemic status and smoking: F = 6.1; p = 0.013. Per 10 years of OC exposure PWV increased by 0.1 m/s (0.02– 0.18; p = 0.013). Use of OC is associated with increased vascular stiffness in women. Current use is associated with increased PWV because OC’s increase blood pressure, long-term use (probably through structural remodelling of the vessels) is an independent determinant of PWV, increasing PWV by 0.10 m/s per 10 years exposure.
HIV-2 Transmission: Implications for Spread of HIV-1
Authors: Thomas R. O'Brien
Journal: JAMA (1994)

<h3>To the Editor.</h3> —Dr De Cock and colleagues<sup>1</sup>summarize data suggesting that human immunodeficiency virus type 2 (HIV2) is less transmissible through sexual intercourse than HIV-1 and conclude that this difference explains the more limited global spread of HIV-2. The authors postulate that the lesser infectivity of HIV-2 is attributable to a relatively lower viral load (and presumably lower levels of virus in semen and female genital secretions) in HIV-2—infected persons with high CD4<sup>+</sup>lymphocyte counts compared with HIV-1—infected persons with similar values. The authors also suggest that HIV-2 may be less transmissible because late-stage disease, a period of increased viral load, develops more slowly with HIV-2 infection than with HIV-1. However, the natural history and transmissibility of these retroviruses may be linked by at least two additional factors. First, quantitative studies of HIV-1—infected persons have shown high viral levels during primary infection,<sup>2</sup>and statistical models suggest that
RAPID METHOD FOR IDENTIFICATION AND ISOLATION OF MENINGOCOCCI FROM THE NASOPHARYNX
Authors: PETER K. OLITSKY
Journal: JAMA (1918)

There is no subject in practical bacteriology being more actively pursued than that of the identification of the meningococcus in plate cultures prepared from the nasopharyngeal mucous membrane. This situation has been brought about through the assembling of the National Army and the National Guard, and the appearance of epidemic meningitis and meningococcus carriers in some of the Army camps. Since the detection and the segregation of the carriers constitute one measure of control of the disease, it is in the highest degree important to reduce to the minimum the time and work incident to their discovery. In this way the separation of the men from their commands is reduced, and the work of the hospital laboratories lightened. The method given here is offered as serving to save time by simplifying the identification of meningococci in mixed cultures in Petri plates. The method proposed employs a fluid medium which serves
Common Approaches to the Measurement of Anxiety
Authors: LAWRENCE C. HARTLAGE
Journal: American Journal of Psychiatry (1972)

Most indexes of anxiety are based on one of four principal techniques; projective estimates, self reports, objective ratings by other persons, and objective behavioral indexes. The author measured 24 adolescents on all four techniques over a three-week period and correlated the results. No correlation approached statistical significance, suggesting that the four techniques do not reflect equivalent measures of anxiety. These results may help to explain the typically poor agreement among studies of anxiety.
Abstract 181: A Feasability Study of Cerebral Oximetry in Cardiac Arrest
Authors: Sam Parnia
Journal: Circulation (2011)

Background: To date there has been no reliable “real time” monitoring available to determine cerebral perfusion during cardiac arrest. Whilst cerebral oximetry using near infra read spectroscopy has been utilized as a non invasive marker of cerebral perfusion during surgery, it has not been integrated into routine cardiac arrest care. Furthermore, the optimal measurement parameters that are associated with return of spontaneous circulation (ROSC) have not been determined. Objectives: To investigate the feasibility of using a commercially available cerebral oximeter (Invos 5100c, Somanetics, Troy, USA) to measure regional brain oxygen saturation(rSO2) during in-hospital cardiac arrest and determine the optimal rS02 parameters that correspond with ROSC. Methods: Cerebral oximetry was applied to 14 in-hospital cardiac arrest patients and continuous data was collected until either ROSC was achieved or CPR was terminated. The mean rSO2, median rSO2, as well as mean and median rSO2 in the last five minutes prior to ROSC or termination of CPR were measured. Results: The use of cerebral oximetry during cardiac arrest and the application of the sensor (completed in 60 ±30s) did not interfere with patient care. ROSC was achieved in 21% (n=3) of cases. Patients with ROSC had a significantly higher total mean (32±5 vs 21±7 p&lt;0.05), median (31±5 vs 20±8 p&lt;0.05), mean rSO2 in final 5 minutes (53±11 vs 17±5 p&lt; 0.0001), median rS02 in final 5 minutes (47±6 vs 17±5 p&lt; 0.0001) than non ROSC patients. In 14% (n=2) of cases, there was a failure to obtain rS02 measurements despite manufacturers recommendations being followed. This observation was only seen in the non ROSC group. Conclusion: The use of cerebral oximetry during cardiac arrest does not interfere with CPR and may be a predictor of ROSC. Although higher mean and median rS02 measurements correlate with ROSC, a rise in rS02 over a five minute period during cardiac arrest may be a better indicator of ROSC. Cerebral oximetry may potentially be used as a marker of organ perfusion as well as ROSC in cardiac arrest.
Abstract 5178: Expression of CD44/CD24 and aldehyde dehydrogenase 1 in resected breast cancer: CD24-positivity predicts early relapse
Authors: Yongwha Moon, Ja Seung Koo, Hyunju Han, Byeong-Woo Park, Seung Il Kim, Seho Park, Joo-Hang Kim, Joo Hyuk Sohn
Journal: Cancer Research (2011)

Abstract Background: CD44+/CD24- or aldehyde dehydrogenase 1 (ALDH1) has been suggested as potential markers for breast cancer stem cells, although little is known about its clinical implications. We evaluated the expression of CD44/CD24 and ALDH1 in breast cancer patients in both ends of the prognostic spectrum. Methods: Of 819 resected breast cancer cohort with positive estrogen receptor, ‘early relapse group’ within 5 years postsurgery and ‘no relapse group’ longer than 10 years postsurgery were defined. Paraffin-embedded tumor tissues were available in 31 early relapsed patients and 68 patients from no relapse group. CD44/CD24 and ALDH1 expression were evaluated with immunohistochemical staining. Positive criteria were designated as more than 15% tumor cell membranous staining for CD44/CD24 and more than 5% tumor cell cytosolic staining for ALDH1. Results: Early relapse group contained higher N stage and higher histologic grade than no relapse group but there were no differences in age, menopauseal status, progesterone receptor status, HER2 status, and T stage between both groups. Phenotypes of CD44/CD24 were CD44+/CD24- in one patient (1%), CD44+/CD24+ in one (1%), CD44-/CD24+ in 12 (12%), and CD44-/CD24- in 67 (68%). Four patients (4%) showed ALDH1-positivity. Due to rarity of CD44-positivity or ALDH1-positivity, staining results were simply dichotomized into CD24-positive (13%, 13/99 patients) and CD24-negative status (87%, 86/99 patients) and only the status of CD24 was further analyzed. CD24-positivity was higher in early relapse group (32%) than in no relapse group (4%). CD24-positivity was associated with negative progesterone receptor (P=0.026), higher N stage (P=0.029), and higher histologic grade (P=0.034). However, in the multivariate logistic regression adjusted by known prognostic factors, CD24-positivity was a still significant predictive factor for early relapse (hazard ratio=8.51; P=0.006). Conclusions: The incidence of CD44+/CD24- and ALDH1-positivity which are potential breast cancer stem cell markers, were low. However, in resected breast cancer, expression of CD24 was a significant predictive factor for early relapse. CD24 is worth further investigation as a novel biomarker. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5178. doi:10.1158/1538-7445.AM2011-5178
Prevalence of Q-T Interval Dispersion in Type 1 Diabetes and Its Relation With Cardiac Ischemia
Authors: Massimo Veglio, Sara Giunti, Linda K. Stevens, John H. Fuller, Paolo Cavallo Perin
Journal: Diabetes Care (2002)

The interlead variation in duration of the Q-T interval on the surface electrocardiogram (Q-T interval dispersion [QTd]) has been shown to predict mortality in type 2 diabetic patients. We evaluated the prevalence of QTd prolongation in the EURODIAB population and its relation to corrected Q-T interval (QTc), sex, age, duration of diabetes, blood glucose control, and complications. RESEARCH DESIGN AND METHODS; A total of 3,042 type 1 diabetic patients were studied. QTc was calculated according to the Bazett's formula; QTc > 0.44 s was considered abnormally prolonged. QTd was calculated using the difference between the maximum and the minimum QTc in any thoracic lead. QTd >0.080 s was considered abnormally prolonged.The prevalence of an increased QTd was 7%. A significant relation was observed between QTd prolongation and diastolic blood pressure (P < 0.05). A higher prevalence of QTd prolongation was observed in patients with ischemic heart disease (P = 0.004), whereas no relationship was observed with retinopathy, albumin excretion rate, or measures of somatic and autonomic neuropathy. QTc and QTd were significantly related (P = 0.001); however, a proportion of patients with normal QTd showed a prolonged QTc (>0.44 s).In patients with type 1 diabetes, QTd is associated with ischemic heart disease and diastolic blood pressure but not neuropathy. Although QTd is statistically related to duration of QTc, increased QTd and increased QTc identify different patients, and their predictive value deserves prospective evaluation.