tbuckley/cabot-search huggingface dataset:
Breast-cancer risk in families with mutations in PALB2.
Authors: Sopik, Narod Sa
Journal: New England Journal of Medicine (2014)

To the Editor: We read the article by Antoniou et al. (August 7 issue)1 because we like to know the penetrance of breast-cancer genes before we recommend surgery. After reading the article, we are unsure of what to tell patients. The simplest message would be that the risk up to 70 years of age is 35%, but this is based on an analysis of patients who received a diagnosis of breast cancer from 1930 to the present. The relevant risk value is that for a woman without breast cancer who is found to have a PALB2 mutation today. Most patients in consultation for breast cancer at Women’s College Hospital were born in 1960 or later. Is their risk of the disease really 6.3 times as high as the risk among women born before 1940 (Table 3 of the article), and how does this translate into a lifetime risk? It is remarkable that the penetrance could increase by a factor of 6 in only 20 years. Personalized medicine is a fine idea, but it is not helpful to be told that “no single set of penetrance estimates applies to all PALB2 mutation carriers” without any clues about how to calculate risk.
Biocompatibility Evolves: Phenomenology to Toxicology to Regeneration
Authors: Lars Crawford, Meghan Wyatt, James Bryers, Buddy Ratner
Journal: Advanced Healthcare Materials (2021)

The word "biocompatibility," is inconsistent with the observations of healing for so-called biocompatible biomaterials. The vast majority of the millions of medical implants in humans today, presumably "biocompatible," are walled off by a dense, avascular, crosslinked collagen capsule, hardly suggestive of life or compatibility. In contrast, one is now seeing examples of implant biomaterials that lead to a vascularized reconstruction of localized tissue, a biological reaction different from traditional biocompatible materials that generate a foreign body capsule. Both the encapsulated biomaterials and the reconstructive biomaterials qualify as "biocompatible" by present day measurements of biocompatibility. Yet, this new generation of materials would seem to heal "compatibly" with the living organism, where older biomaterials are isolated from the living organism by the dense capsule. This review/perspective article will explore this biocompatibility etymological conundrum by reviewing the history of the concepts around biocompatibility, today's standard methods for assessing biocompatibility, a contemporary view of the foreign body reaction and finally, a compendium of new biomaterials that heal without the foreign body capsule. A new definition of biocompatibility is offered here to address advances in biomaterials design leading to biomaterials that heal into the body in a facile manner.
Re: Contrasting Epidemiology and Clinicopathology of Female Breast Cancer in Asians vs the US Population
Authors: Hyuna Sung, Philip S Rosenberg, Xiaohong R Yang
Journal: JNCI Journal of the National Cancer Institute (2019)

The article by Lin et al. (1) presented comparisons of agespecific probabilities of breast cancer subtypes between Asian and US women using data from eight hospital-based cancer registries in East Asian countries and the Surveillance, Epidemiology, and End Results Program.The study found a higher proportion of estrogen-receptor (ER)-positive and lower proportion of triple-negative breast cancer in younger (40-49 years) East Asian women than in US women.Similar patterns were observed between Asian Americans (Chinese, Japanese, and Korean Americans) and US non-Hispanic whites (whites).The authors therefore proposed that the identified patterns may signify an underlying racial effect on the etiology of breast cancer and that estrogen plays an important etiologic role in younger Asian women.However, relative proportions of cancer subtypes may neither translate into absolute risks nor reveal the underlying tumor biology.To compare absolute risks in relation to age and subtype, we calculated differences in age-specific incidence rates of breast cancer subtypes between Asian Pacific Islanders (APIs) and whites in the Surveillance, Epidemiology, and End Results Program (2). Figure 1 shows age-specific incidence rates and APIsto-whites incidence rate ratios (IRRs) for ER-positive, HER2-positive, triple-negative, and histological grade III breast cancer subtypes.Rates among APIs did not exceed those among whites across all age groups and subtypes, apart from HER2-positive cancers at ages 40-59 years.Among younger women (20-49 years), rates for ER-positive cancers among APIs were comparable to or lower than those among whites (IRR ¼ 0.89-0.94).This result suggests that, despite the higher proportion of ER-positive cancers among younger APIs, rates of young ER-positive cancers were not any greater among APIs than among whites.Moreover, greater incidence gaps for ER-positive cancers occurred among older women (50 years; IRR ¼ 0.52-0.84)between populations, demonstrating an important asymmetry in disease risk among older women than among younger women.These results are consistent with our previous study conducted in Sarawak, Malaysia, in Institute.
Vascular prostaglandin and thromboxane production in a canine model of myocardial ischemia.
Authors: J MSchmitz, P GApprill, L MBuja, J TWillerson, W BCampbell
Journal: Circulation Research (1985)

Whereas numerous studies have investigated the role of prostacyclin and thromboxane A2 in the maintenance of coronary blood flow, most of these have focused on normal vessels. In the present investigation, we examined the prostaglandin- and thromboxane-synthesizing capacity of isolated coronary artery segments obtained from the site of a critical coronary artery stenosis. Cyclic flow variations were produced by placing a hard cylindrical constrictor on the proximal left anterior descending coronary artery in open-chest, anesthetized dogs. Cyclic flow variations are characterized by progressive declines in coronary blood flow, interrupted by sudden spontaneous restorations of flow. After cyclic flow variations had been induced, the hearts were removed, and the left anterior descending and circumflex coronary arteries were dissected. The vessels were cut into segments and incubated in the presence of increasing concentrations of arachidonic acid (10(-4)-10(-6) M). The synthesis of prostaglandin E2, thrombox...
Abstract #1471: HS-1793, a novel resveratrol analogue, induces growth inhibition, apoptosis, and down-regulation of hypoxia-induced expressions of HIF-1\#945; in human hepatocellular carcinoma cells
Authors: Min Young Kim, Sang Eun Park, Mohammad Akbar Hossain, Dong Hwan Kim, Jin-Ah Kim, Hongsuk Suh, Gi Young Kim, Yung Hyun Choi, Nam Deuk Kim
Journal: Cancer Research (2009)

Resveratrol, a polyphenolic natural compound found in grapes and various herbs, has been reported to show chemopreventive capacity. In the present study, 4-(6-hydroxy-2-naphthyl)-1,3-bezendiol (HS-1793), a novel resveratrol analogue, was found to induce growth inhibition, apoptosis, and down-regulation of HIF-1\#945; in HepG2 human hepatocellular carcinoma cells. HS-1793 inhibited the growth of HepG2 cells in a concentration-dependent manner. HS-1793 showed more cytotoxic effects on HepG2 cells than resveratrol. Further studies revealed that HS-1793 induced DNA fragmentation. Furthermore, morphological characterizations such as apoptotic bodies and membrane blebs were also observed. The growth inhibitory effects of HS-1793 were mediated through the cell-cycle arrest; upregulation of p21CIP1/WAF1, p53, and Bax; down-regulation of cyclin D1, cyclin E, Bcl-2, and activation of caspases. HS-1793 suppressed the activation of several transcription factors, including NF-\#954;B, Egr-1, and down-regulated genes such as COX-2 and VEGF. We also investigated the effect of HS-1793 on the expression of hypoxia-inducible factor-1\#945; (HIF-1\#945;). HIF-1\#945; is overexpressed in many human tumors, and their metastases, and is closely associated with a more aggressive tumor phenotype. We found that HS-1793 inhibited hypoxia (1.0% oxygen) induced HIF-1\#945; protein level dose-dependently. Overall, HS-1793 proved to be even more potent than resveratrol in cytotoxic test against HepG2 cells and also rapidly down-regulated the expression level of HIF-1\#945;. These findings suggest that HS-1793 seems to be a promising candidate for future evaluation of chemopreventive activity for liver cancer. [This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (R01-2006-000-11117-0)].  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1471.
Safety of the Use of Radioactive Iodine in Patients With Hyperthyroidism—Reply
Authors: Cari M. Kitahara, Amy Berrington de González, Dale L. Preston
Journal: JAMA Internal Medicine (2019)

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Rapid decline of neutralizing antibodies is associated with decay of IgM in adults recovered from mild COVID-19
Authors: Whitney E. Harrington, Olesya Trakhimets, Daniela V. Andrade, Nicholas Dambrauskas, Andrew Raappana, Yonghou Jiang, John Houck, William Selman, Ashton Yang, Vladimir Vigdorovich, Winnie Yeung, Micaela Haglund, Jackson Wallner, Alyssa Oldroyd, Samantha Hardy, Samuel W.A. Stewart, Ana Gervassi, Wes Van Voorhis, Lisa Frenkel, D. Noah Sather
Journal: Cell Reports Medicine (2021)

The fate of protective immunity following mild severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection remains ill defined. Here, we characterize antibody responses in a cohort of participants recovered from mild SARS-CoV-2 infection with follow-up to 6 months. We measure immunoglobulin A (IgA), IgM, and IgG binding and avidity to viral antigens and assess neutralizing antibody responses over time. Furthermore, we correlate the effect of fever, gender, age, and time since symptom onset with antibody responses. We observe that total anti-S trimer, anti-receptor-binding domain (RBD), and anti-nucleocapsid protein (NP) IgG are relatively stable over 6 months of follow-up, that anti-S and anti-RBD avidity increases over time, and that fever is associated with higher levels of antibodies. However, neutralizing antibody responses rapidly decay and are strongly associated with declines in IgM levels. Thus, while total antibody against SARS-CoV-2 may persist, functional antibody, particularly IgM, is rapidly lost. These observations have implications for the duration of protective immunity following mild SARS-CoV-2 infection.
Junctional pacemakers in man. Response to overdrive suppression with and without parasympathetic blockade.
Authors: O SNarula, J TNarula
Journal: Circulation (1978)

This study analyzes the response to overdrive suppression of junctional pacemakers (JP) and correlates it with symptoms in 21 patients. Junctional rhythm (JR) was seen in 5 patients with intact A-V conduction, and in 16 with complete heart block, the JPs were located proximal to or within the His bundle (BH). Junctional recovery time (JRT) was measured following atrial or ventricular pacing during control and after atropine (2-2.5 mg). Control cycle length of the JR ranged from 835-2100 msec (mean 1402) and the corrected JRT (CJRT) ranged from 75 to greater than or equal to 7510 msec (mean 2966). Following atropine, the cycle length ranged from 660 to 2000 msec (mean 1115) and the CJRT ranged from 90 to greater than 6000 msec (mean 2050). All symptomatic patients were treated with permanent ventricular demand pacemakers and followed clinically from 6-72 months (mean = 35). Symptomatic patients could not be differentiated from asymptomatic patients on the basis of control heart rates, chronotropic response...
Electrophysiologic effects on combined autonomic blockade in patients with sinus node disease.
Authors: J MDesai, M MScheinman, H CStrauss, BMassie, JO'Young
Journal: Circulation (1981)

Thirty-two patients were studied before and after i.v. administration of 0.15-0.20 mg/kg of propranolol. Twenty-one of the 32 underwent combined autonomic blockade with the additional infusion of 0.04 mg of atropine. Twenty other patients with sinus node disease underwent electrophysiologic studies both before and after i.v. administration of 0.04 mg of atropine alone. Spontaneous cycle length, maximal corrected sinus node recovery time, sinoatrial conduction time, secondary pauses and intrinsic heart rate were measured. Secondary pauses were more common in those with abnormal intrinsic heart rates, and they did not correlate with changes in maximal corrected sinus node recovery time or sinoatrial conduction time. In patients with normal intrinsic heart rate, abnormal test measurements usually returned to normal after combined blockade (hypervagotonia); however, some patients showed a new abnormality after propranolol that was not reversible with atropine (catecholamine-dependent). Abnormal test responses...
Patient’S Perspective On The Implementation Of Measures To Contain The Sars-Cov-2 Pandemic In A Portuguese Gastroenterology Department
Authors: C Gomes, A Ponte, R Pinho, JC Silva, E Afecto, J Correia, J Carvalho
Journal: Endoscopy (2021)

Aims As the COVID-19 pandemic races around the world, hospital departments had to adapt their activities, which could ultimately jeopardize patient's best interests. Our gastroenterology department of Centro Hospitalar Vila Nova de Gaia/Espinho (CHVNG/E) was forced to undergo dynamic changes and adjusted its clinical practice. The aim of this paper is to evaluate the patient's perspective to the implementation of SARS-CoV-2 measures in our department.
Mechanisms of pulmonary edema induced by tumor necrosis factor-alpha.
Authors: D CHocking, P GPhillips, T JFerro, AJohnson
Journal: Circulation Research (1990)

We tested the hypothesis that human recombinant tumor necrosis factor-alpha (TNF) promotes pulmonary edema by neutrophil-dependent effects on the pulmonary vasculature. The isolated guinea pig lung was perfused with phosphate-buffered Ringer's solution with or without human neutrophils. The infusion of neutrophils (9 x 10(6) total) into lungs isolated after the in vivo administration of TNF (3.2 x 10(5) units/kg) resulted in weight gain (+1.951 +/- 0.311 g versus -0.053 +/- 0.053 g in control) and an increase in the lung (wet-dry)-to-dry weight ratio (8.3 +/- 0.5 versus 6.0 +/- 0.2 in control), indicating the formation of pulmonary edema. The neutrophil-dependent pulmonary edema induced by TNF was associated with a combination of increased capillary permeability (capillary filtration coefficient [Kf,c], 0.170 +/- 0.048 g/min/cm H2O/g at 30 minutes versus 0.118 +/- 0.008 g/min/cm H2O/g at baseline) and increased pulmonary capillary pressure (Ppc, 12.8 +/- 0.8 cm H2O at 60 minutes versus 6.0 +/- 0.3 cm H2O ...
Developmental changes in cardiac myocyte calcium regulation.
Authors: T KChin, W FFriedman, T SKlitzner
Journal: Circulation Research (1990)

Developmental changes in the contributions of transsarcolemmal Ca2+ influx and Ca2+ release from intracellular storage sites to myocardial contraction were evaluated in isolated ventricular myocytes from neonatal (aged 1-7 days) and adult (aged 8-10 weeks) New Zealand White rabbits. Contractions ceased in one beat when extracellular Ca2+ was decreased from 1mM to micromolar levels using a rapid perfusion technique. On reperfusion with 1 mM Ca2+, recovery of control contraction amplitude occurred after significantly fewer beats in neonatal myocytes compared with adult myocytes, and after 1 minute compared with 5 minutes of reduced Ca2+. After 15 minutes of perfusion with either 1 or 10 microM ryanodine, contraction amplitude decreased in both age groups, but the decrease was significantly greater in adults than in neonates. These experiments indicate that isolated ventricular myocytes may be used in the study of developmental changes in intracellular Ca2+ regulation. Results suggest that cardiac contractio...
TCTAP A-002 Limitation of Angiographic Parameters in Predicting Residual Ischemia After Drug-eluting Stent Implantation
Authors: Jaewook Chung, Jinlong Zhang, Doyeon Hwang, Seokhun Yang, Jeehoon Kang, Jung-Kyu Han, Han-Mo Yang, Kyung Woo Park, Joo Myung Lee, Chang-Wook Nam, Eun-Seok Shin, Joon-Hyung Doh, Fei Ye, Shaoliang Chen, Tsunekazu Kakuta, Bon-Kwon Koo, Hyo-Soo Kim
Journal: Journal of the American College of Cardiology (2021)
Idiopathic Pulmonary Hemosiderosis
Authors: A. S. Cooper
Journal: New England Journal of Medicine (1960)

IDIOPATHIC pulmonary hemosiderosis is an uncommon disease and is the result of recurrent hemorrhages into the lungs. The cause of these hemorrhages is uncertain. The diagnosis is often made only at autopsy. Most cases occur in children.The occurrence of this condition in adult life is rare. The first case described was by Borsos-Nachtnebel1 (1942), although Steiner2 (1954) casts doubt on its authenticity. Kerley3 (1951) gives a brief description of 5 adult cases. Seventeen other cases in which symptoms appeared in patients over the age of eighteen have been found in the literature.4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 The only patients over the age of . . .
Cytokeratin-Positive Cells in the Bone Marrow and Survival of Patients with Stage I, II, or III Breast Cancer
Journal: New England Journal of Medicine (2000)

Background Cytokeratins are specific markers of epithelial cancer cells in bone marrow. We assessed the influence of cytokeratin-positive micrometastases in the bone marrow on the prognosis of women with breast cancer. Methods We obtained bone marrow aspirates from both upper iliac crests of 552 patients with stage I, II, or III breast cancer who underwent complete resection of the tumor and 191 patients with nonmalignant disease. The specimens were stained with the monoclonal antibody A45-B/B3, which binds to an antigen on cytokeratins. The median follow-up was 38 months (range, 10 to 70). The primary end point was survival. Results Cytokeratin-positive cells were detected in the bone marrow specimens of 2 of the 191 control patients with nonmalignant conditions (1 percent) and 199 of the 552 patients with breast cancer (36 percent). The presence of occult metastatic cells in bone marrow was unrelated to the presence or absence of lymph-node metastasis (P=0.13). After four years of follow-up, the presence of micrometastases in bone marrow was associated with the occurrence of clinically overt distant metastasis and death from cancerrelated causes (P<0.001), but not with locoregional relapse (P=0.77). Of 199 patients with occult metastatic cells, 49 died of cancer, whereas of 353 patients without such cells, 22 died of cancer-related causes (P<0.001). Among the 301 women without lymphnode metastases, 14 of the 100 with bone marrow micrometastases died of cancer-related causes, as did 2 of the 201 without bone marrow micrometastases (P<0.001). The presence of occult metastatic cells in bone marrow, as compared with their absence, was an independent prognostic indicator of the risk of death from cancer (relative risk, 4.17; 95 percent confidence interval, 2.51 to 6.94; P<0.001), after adjustment for the use of systemic adjuvant chemotherapy. Conclusions The presence of occult cytokeratinpositive metastatic cells in bone marrow increases the risk of relapse in patients with stage I, II, or III breast cancer. (N Engl J Med 2000;342:525-33.)
血管造影で正常な冠状動脈傷害のin vivoでの定量的な組織の性質および危険因子との関係 統合後方散乱血管内超音波検査を用いた研究
Authors: Sano Keiji, Kawasaki Masanori, Okubo Munenori, Yokoyama Haruko, Ito Yoko, Murata Ichijiro, Kawai Takao, Tsuchiya Kunihiko, Nishigaki Kazuhiko, Takemura Genzou, Minatoguchi Shinya, Zhou Xiangrong, Fujita Hiroshi, Fujiwara Hisayoshi
Journal: Circulation (2005)
Electrophysiological study of the action of angiotensin II on the rat myometrium.
Authors: GHamon, MWorcel
Journal: Circulation Research (1979)

Angiotensin II (A II) produces a contraction of visceral and vascular smooth muscles of different species. The accompanying electrophysiological changes were measured on strips of rat myometrium at 35 degrees C using the double sucrose-gap technique. A II at concentrations from 5 x 10(-10) to 10(-6)M produces a depolarization and an increase in membrane conductance. This increase in membrane conductance is not membrane potential dependent since it is observed even when the membrane potential is maintained at the resting level. When all Na + in the test solution is replaced by either Li + or Mg (2+), the depolarizing effect of 10(-6)M A II is either markedly reduced or abolished. Under these conditions, A II produces a small initial hyperpolarization, which is modified by external potassium concentration changes and abolished by tetraethylammonium chloride. When all Cl- is replaced by either NO (-3) or cyclohexanesulfamate, A II (10(-6) M) still produces a 20-m V depolarization. The removal of extracellula...
Determination of transmural location of onset of activation from cardiac surface electrograms.
Authors: M JBurgess, R LLux, P RErshler, RMenlove
Journal: Circulation (1990)

Methods of estimating depth of origin of ventricular activation from cardiac surface electrograms were evaluated in experiments on eight dogs. The ventricles were paced via multielectrode needle arrays placed transmurally in from four to six locations in the wall of the left ventricle. A multiplexed data-recording system was used to simultaneously record from 64 unipolar cardiac surface electrodes during pacing at each multielectrode needle site. The four indexes evaluated were the maximum and average gradients of activation isochrones around the site of earliest epicardial activation, the QRS area at the site of earliest epicardial activation, the interval between the QRS onset computed from all 64 epicardial surface electrograms, and the time of the minimum dV/dt in the electrogram displaying the earliest epicardial activation time (t(ee)-t(rmso) interval). Correlation coefficients between depth of stimulation and average and maximum gradients of isochrones, QRS area at the site of earliest epicardial a...