tbuckley/cabot-search huggingface dataset:
Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma: Multi-Institutional Experience
Authors: Tristan D. Yan, Marcello Deraco, Dario Baratti, Shigeki Kusamura, Dominique Elias, Olivier Glehen, François N. Gilly, Edward A. Levine, Perry Shen, Faheez Mohamed, Brendan J. Moran, David L. Morris, Terence C. Chua, Pompiliu Piso, Paul H. Sugarbaker
Journal: Journal of Clinical Oncology (2009)

Purpose This multi-institutional registry study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for diffuse malignant peritoneal mesothelioma (DMPM). Patients and Methods A multi-institutional data registry that included 405 patients with DMPM treated by a uniform approach that used CRS and HIPEC was established. The primary end point was overall survival. The secondary end point was evaluation of prognostic variables for overall survival. Results Follow-up was complete in 401 patients (99%). The median follow-up period for the patients who were alive was 33 months (range, 1 to 235 months). The mean age was 50 years (standard deviation [SD], 14 years). Three hundred eighteen patients (79%) had epithelial tumors. Twenty-five patients (6%) had positive lymph nodes. The mean peritoneal cancer index was 20. One hundred eighty-seven patients (46%) had complete or near-complete cytoreduction. Three hundred seventy-two patients (92%) received HIPEC. One hundred twenty-seven patients (31%) had grades 3 to 4 complications. Nine patients (2%) died perioperatively. The mean length of hospital stay was 22 days (SD, 15 days). The overall median survival was 53 months (1 to 235 months), and 3- and 5-year survival rates were 60% and 47%, respectively. Four prognostic factors were independently associated with improved survival in the multivariate analysis: epithelial subtype (P &lt; .001), absence of lymph node metastasis (P &lt; .001), completeness of cytoreduction scores of CC-0 or CC-1 (P &lt; .001), and HIPEC (P = .002). Conclusion The data suggest that CRS combined with HIPEC achieved prolonged survival in selected patients with DMPM.
Identification and management of unusual pathogens in cystic fibrosis
Authors: J Stuart Elborn
Journal: Journal of the Royal Society of Medicine (2008)

The role of infecting organisms in the pathogenesis of lung disease is well established. Organisms such as Staphylococcus aureus, non-capsulate Haemophilus influenzae, Pseudomonas aeruginosa, Burkholderia cepacia complex (Bcc) and respiratory viruses are well recognized as important pathogens which drive inflammatory responses and lung injury in cystic fibrosis (CF).1

Aggressive treatment of airway infection in CF has been one of the key factors in improving long-term survival, and many patients with CF are treated very aggressively with antibiotics to maintain airway sterility.2,3 In the last 10–15 years a number of organisms have been identified that are likely to play a role in airways infection in CF. An increasing number of species have been identified as dominant pathogens in the airway and in addition a wide range of co-infecting organisms have also now been identified.1,4,5
Modulating Endogenous NQO1 Levels Identifies Key Regulatory Mechanisms of Action of β-Lapachone for Pancreatic Cancer Therapy
Authors: Long Shan Li, Erik A. Bey, Ying Dong, Jieru Meng, Biswanath Patra, Jingsheng Yan, Xian-Jin Xie, Rolf A. Brekken, Carlton C. Barnett, William G. Bornmann, Jinming Gao, David A. Boothman
Journal: Clinical Cancer Research (2011)

Pancreatic cancer is the fourth leading cause of cancer-related deaths, in which the 5-year survival rate is less than 5%. Current standard of care therapies offer little selectivity and high toxicity. Novel, tumor-selective approaches are desperately needed. Although prior work suggested that β-lapachone (β-lap) could be used for the treatment of pancreatic cancers, the lack of knowledge of the compound's mechanism of action prevented optimal use of this agent.We examined the role of NAD(P)H:quinone oxidoreductase-1 (NQO1) in β-lap-mediated antitumor activity, using a series of MIA PaCa-2 pancreatic cancer clones varying in NQO1 levels by stable shRNA knockdown. The antitumor efficacy of β-lap was determined using an optimal hydroxypropyl-β-cyclodextran (HPβ-CD) vehicle formulation in metastatic pancreatic cancer models.β-Lap-mediated cell death required ∼90 enzymatic units of NQO1. Essential downstream mediators of lethality were as follows: (i) reactive oxygen species (ROS); (ii) single-strand DNA breaks induced by ROS; (iii) poly(ADP-ribose)polymerase-1 (PARP1) hyperactivation; (iv) dramatic NAD(+)/ATP depletion; and (v) programmed necrosis. We showed that 1 regimen of β-lap therapy (5 treatments every other day) efficaciously regressed and reduced human pancreatic tumor burden and dramatically extended the survival of athymic mice, using metastatic pancreatic cancer models.Because NQO1 enzyme activities are easily measured and commonly overexpressed (i.e., >70%) in pancreatic cancers 5- to 10-fold above normal tissue, strategies using β-lap to efficaciously treat pancreatic cancers are indicated. On the basis of optimal drug formulation and efficacious antitumor efficacy, such a therapy should be extremely safe and not accompanied with normal tissue toxicity or hemolytic anemia.
Sex Hormone Levels and Risk of Breast Cancer With Estrogen Plus Progestin
Authors: G. N. Farhat, N. Parimi, R. T. Chlebowski, J. E. Manson, G. Anderson, A. J. Huang, E. Vittinghoff, J. S. Lee, A. Z. LaCroix, J. A. Cauley, R. Jackson, D. Grady, D. S. Lane, L. Phillips, M. S. Simon, S. R. Cummings
Journal: JNCI Journal of the National Cancer Institute (2013)

Although high endogenous sex hormone levels and estrogen plus progestin (E+P) therapy are associated with increased breast cancer risk, it is unknown whether pretreatment levels of sex hormones modify E+P effect on breast cancer. We conducted a nested case–control study within the Women's Health Initiative randomized clinical trial of E+P. The trial enrolled 16608 postmenopausal women aged 50 to 79 years with intact uterus and no breast cancer history. During a mean of 5.6 years of follow-up, 348 incident breast cancer case subjects were identified and matched with 348 control subjects. Case and control subjects had their sex hormone levels measured at baseline (estrogens, testosterone, progesterone, and sex hormone–binding globulin [SHBG]) and year 1 (estrogens and SHBG) using sensitive assays. All statistical tests were two-sided. Statistically significant elevations in breast cancer risk were seen with greater pretreatment levels of total estradiol ( Ptrend = .04), bioavailable estradiol ( Ptrend = .03), estrone ( Ptrend = .007), and estrone sulfate ( Ptrend = .007). E+P increased all measured estrogens and SHGB at year 1 (all P < .001). The effect of E+P on breast cancer risk was strongest in women whose pretreatment levels of total estradiol, bioavailable estradiol, and estrone were in the lowest quartiles. For example, the odds ratio for E+P relative to placebo was 2.47 (95% confidence interval [CI] = 1.28 to 4.79) in the lowest total estradiol quartile, compared with 0.96 (95% CI = 0.44 to 2.09) in the highest total estradiol quartile; Pinteraction = .04). Women with lower pr-treatment endogenous estrogen levels were at greater risk of breast cancer during E+P therapy compared with those with higher levels. Further studies are warranted to confirm these findings.
Fluid Mechanics of Heart Valves
Authors: Ajit P. Yoganathan, Zhaoming He, S. Casey Jones
Journal: Annual Review of Biomedical Engineering (2004)

Valvular heart disease is a life-threatening disease that afflicts millions of people worldwide and leads to approximately 250,000 valve repairs and/or replacements each year. Malfunction of a native valve impairs its efficient fluid mechanic/hemodynamic performance. Artificial heart valves have been used since 1960 to replace diseased native valves and have saved millions of lives. Unfortunately, despite four decades of use, these devices are less than ideal and lead to many complications. Many of these complications/problems are directly related to the fluid mechanics associated with the various mechanical and bioprosthetic valve designs. This review focuses on the state-of-the-art experimental and computational fluid mechanics of native and prosthetic heart valves in current clinical use. The fluid dynamic performance characteristics of caged-ball, tilting-disc, bileaflet mechanical valves and porcine and pericardial stented and nonstented bioprostheic valves are reviewed. Other issues related to heart valve performance, such as biomaterials, solid mechanics, tissue mechanics, and durability, are not addressed in this review.
Structural remodeling of cardiac myocytes in patients with ischemic cardiomyopathy.
Authors: A M Gerdes, S E Kellerman, J A Moore, K E Muffly, L C Clark, P Y Reaves, K B Malec, P P McKeown, D D Schocken
Journal: Circulation (1992)

BACKGROUND Chronic ischemic heart disease may lead to ventricular dilation and congestive heart failure (ischemic cardiomyopathy [ICM]). The changes in cardiac myocyte shape associated with this dilation, however, are not known. METHODS AND RESULTS Left ventricular myocyte dimensions were assessed in cells isolated from explanted human hearts obtained from patients with ICM (n = 6) who were undergoing heart transplantation. Cells were also examined from three nonfailing donor hearts with normal coronary arteries (NCA). Compared with cells from patients with NCA, myocyte length was 40% longer in hearts from patients with ICM (197 +/- 8 versus 141 +/- 9 microns, p less than 0.01), cell width was not significantly different, and cell length/width ratio was 49% greater (11.2 +/- 0.9 versus 7.5 +/- 0.6, p less than 0.01). Sarcomere length was the same in myocytes from both groups. The extent of myocyte lengthening is comparable to the increase in end-diastolic diameter commonly reported in patients with ICM. CONCLUSIONS These data suggest that increased myocyte length (an intracellular event), instead of myocyte slippage (an extracellular event), is largely responsible for the chamber dilation in ICM. Furthermore, maladaptive remodeling of myocyte shape (e.g., increased myocyte length/width ratio) may contribute to the elevated wall stress (e.g., increased chamber radius/wall thickness) in ICM.
Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study
Authors: Christopher P Cannon, Robert A Harrington, Stefan James, Diego Ardissino, Richard C Becker, Håkan Emanuelsson, Steen Husted, Hugo Katus, Matyas Keltai, Nardev S Khurmi, Frederic Kontny, Basil S Lewis, Philippe Gabriel Steg, Robert F Storey, Daniel Wojdyla, Lars Wallentin
Journal: The Lancet (2010)
Effect of decreased O2 supply to tissue on the lactate:pyruvate ratio in blood
Authors: William A. Neill, Peter E. Jensen, Gerald B. Rich, John D. Werschkul
Journal: Journal of Clinical Investigation (1969)

Experiments were performed with trained conscious dogs with permanently implanted intravascular catheters. With the dogs in a basal resting state, the concentrations of lactate (L) and pyruvate (P) in arterial blood fluctuated widely from day to day, whereas their concentration ratio (L/P) remained relatively constant. By contrast, decrease in tissue O2 supply induced by severe chronic anemia increased the arterial blood L/P, specifically, with only random accompanying changes in the lactate or pyruvate concentrations themselves.
Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation
Authors: Hiromi Iwasaki, Chamorro Somoza, Hirokazu Shigematsu, Estelle A. Duprez, Junko Iwasaki-Arai, Shin-ichi Mizuno, Yojiro Arinobu, Kristin Geary, Pu Zhang, Tajhal Dayaram, Maris L. Fenyus, Shannon Elf, Susan Chan, Philippe Kastner, Claudia S. Huettner, Richard Murray, Daniel G. Tenen, Koichi Akashi
Journal: Blood (2005)
Galectin-3 Regulates Mitochondrial Stability and Antiapoptotic Function in Response to Anticancer Drug in Prostate Cancer
Authors: Tomoharu Fukumori, Natsuo Oka, Yukinori Takenaka, Pratima Nangia-Makker, Essam Elsamman, Toshinori Kasai, Masayuki Shono, Hiro-omi Kanayama, Julie Ellerhorst, Reuben Lotan, Avraham Raz
Journal: Cancer Research (2006)

Abstract Prostate cancer is one of the malignant tumors which exhibit resistance to anticancer drugs, at least in part due to enhanced antiapoptotic mechanisms. Therefore, the understanding of such mechanisms should improve the design of chemotherapy against prostate cancer. Galectin-3 (Gal-3), a multifunctional oncogenic protein involved in the regulation of tumor proliferation, angiogenesis, and apoptosis has shown antiapoptotic effects in certain cell types. Here, we show that the expression of exogenous Gal-3 in human prostate cancer LNCaP cells, which do not express Gal-3 constitutively, inhibits anticancer drug–induced apoptosis by stabilizing the mitochondria. Thus, Gal-3-negative cells showed 66.31% apoptosis after treatment with 50 μmol/L cis-diammine-dichloroplatinum for 48 hours, whereas two clones of Gal-3-expressing cells show only 2.92% and 1.42% apoptotic cells. Similarly, Gal-3-negative cells showed 43.8% apoptosis after treatment with 300 μmol/L etoposide for 48 hours, whereas only 15.38% and 14.51% of Gal-3-expressing LNCaP cells were apoptotic. The expression of Gal-3 stimulated the phosphorylation of Ser112 of Bcl-2-associated death (Bad) protein and down-regulated Bad expression after treatment with cis-diammine-dichloroplatinum. Gal-3 also inhibited mitochondrial depolarization and damage after translocation from the nuclei to the cytoplasm, resulting in inhibition of cytochrome c release and caspase-3 activation. These findings indicate that Gal-3 inhibits anticancer drug–induced apoptosis through regulation of Bad protein and suppression of the mitochondrial apoptosis pathway. Therefore, targeting Gal-3 could improve the efficacy of anticancer drug chemotherapy in prostate cancer. (Cancer Res 2006; 66(6): 3114-9)
Effectiveness of an Oral, Nonmercurial Diuretic
Authors: BENJAMIN WAINFELD, JACOB J. YARVIS, I. RICHARD SCHWARTZ
Journal: Circulation (1958)

In a previous trial of aminometramid on 30 patients with peripheral edema, 19 became refractory to the drug. These 19 patients and another group of 16 with peripheral edema or ascites were placed on another nonmercurial diuretic aminoisometradine, which had shown promise in previous studies in animals and man. This group of 35 patients who had previously required frequent injections of mercurial diuretics were treated with the new diuretic for at least 8 months. Conclusions of this study are presented.
Haemodynamically unstable pulmonary embolism in the RIETE Registry: systolic blood pressure or shock index?
Authors: R. Otero, J. Trujillo-Santos, A. Cayuela, C. Rodríguez, M. Barron, J. J. Martín, M. Monreal
Journal: European Respiratory Journal (2007)

Patients with acute pulmonary embolism (PE) presenting with haemodynamic instability have the worst prognosis. However, what is understood by haemodynamic instability has not been clearly defined. The Registro Informatizado de la Enfermedad Tromboembólica (RIETE) is an ongoing registry of consecutive patients with symptomatic, objectively confirmed, acute deep vein thrombosis or PE. The present authors compared the predictive value of a systolic blood pressure (SBP) value of &lt;100 mmHg and &lt;90 mmHg and the shock index (cardiac frequency divided by SBP) on 30-day mortality in consecutive patients with PE. As of May 2006, 6,599 patients with PE were enrolled in the study. Of these, 417 (6.3%) died within 30 days: 153 of the initial PE, 29 of recurrent PE and 235 due to other causes. Of the 417 individuals who died, 127 (30%) had a positive shock index, 60 (14%) had SBP &lt;100 mmHg and 33 (7.9%) had SBP &lt;90 mmHg. On multivariate analysis any of the three parameters were independently associated with an increased mortality. The shock index had a higher sensitivity (30.5 versus 14.4 and 7.9% for SBP &lt;100 mmHg and &lt;90 mmHg, respectively) but lower specificity (86.3 versus 93.0 and 96.6). All three measures of haemodynamic instability are independent predictors of 30-day mortality. However, while the shock index had the highest sensitivity, a systolic blood pressure value &lt;90 mmHg had the highest specificity.
Mitochondria act as a reservoir for the basic amine HIPDM in the lung
Authors: M Miniati, A Paci, F Cocci, G Ciarimboli, S Monti, M Pistolesi
Journal: European Respiratory Journal (1996)

The lungs are a site for the uptake, accumulation, and storage of exogenous basic amines. The compound N-N-N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3 propanediamine (HIPDM) is a basic amine that can be labelled with radioactive iodine and detected by external counting. Intravenously injected 123I-HIPDM is extracted by the human lung, where it is retained in a slowly effluxable pool. In the present study, we measured HIPDM lung kinetics and subcellular distribution in rabbits given i.v. 125I-HIPDM. Rabbits were killed from 2 min to 5 h after injection, and the radioactivity retained in their lungs was measured. Subcellular lung fractions (nuclear, mitochondrial, lysosomal, microsomal and postmicrosomal supernatant) were assayed for HIPDM radioactivity, protein content, and distribution of specific marker enzymes. HIPDM lung clearance in rabbits was nearly identical to that of humans. Virtually all the HIPDM radioactivity in lungs (98+/-1%) was associated with subcellular membranous structures. The highest HIPDM specific radioactivity was found in the mitochondrial fraction, and the subcellular distribution profile closely resembled that of the mitochondrial marker enzyme succinate cytochrome c reductase. No redistribution of HIPDM among subcellular compartments was observed over a 5 h period after injection. The data indicate that mitochondria act as reservoir for HIPDM in the lungs and contribute to the pulmonary persistence of this compound. HIPDM can be used to investigate the pulmonary uptake of basic amines in health and in lung disease.
Dolphin play: Evidence for cooperation and culture?
Authors: Stan A. Kuczaj, Lauren E. Highfill
Journal: Behavioral and Brain Sciences (2005)

We agree that human culture is unique. However, we also believe that an understanding of the evolution of culture requires a comparative approach. We offer examples of collaborative behaviors from dolphin play, and argue that consideration should be given to whether various forms of culture are best viewed as falling along a continuum or as discrete categories.
Stimulation of putrescine production by epidermal growth factor in rat liver after partial hepatectomy
Authors: Sumiko Nagoshi, Tomoaki Tomiya, Yuzuru Sato, Yuji Oka, Itsuro Ogata, Kenji Fujiwara
Journal: Hepatology (1991)

When epidermal growth factor was given to rats after partial hepatectomy, hepatic putrescine content was significantly increased at 4, 6 and 10 hr compared with control rats. Ornithine decarboxylase activity was also increased. Hepatic ornithine decarboxylase messenger RNA content was significantly greater than control levels at 2 hr after epidermal growth factor treatment, but not at 10 hr, when the amount of ornithine decarboxylase messenger RNA in control animals was four times that at 2 hr. When actinomycin D was administered 6 hr after partial hepatectomy, hepatic ornithine decarboxylase activity at 10 hr was reduced to half the control levels. This reduction was attenuated by epidermal growth factor treatment at 6 and 8 hr. Hepatic immunoreactive ornithine decarboxylase protein content showed a highly positive correlation with hepatic ornithine decarboxylase activity at 4, 6 and 10 hr, irrespective of epidermal growth factor treatment. Hepatic spermidine N1-acetyltransferase activity was significantly increased at 6 hr compared with control rats. These results suggest that, after partial hepatectomy in rats, exogenous epidermal growth factor may stimulate hepatic putrescine production by increasing ornithine decarboxylase messenger RNA content and altering posttranscriptional ornithine decarboxylase regulation, as well as enhancing spermidine N1-acetyltransferase activity. (HEPATOLOGY 1991;14:901–905).
Prevalence of Kaposi's sarcoma associated herpesvirus infection measured by antibodies to recombinant capsid protein and latent immunofluorescence antigen
Authors: Guy R Simpson, Thomas F Schulz, Denise Whitby, Pamela M Cook, Chris Boshoff, Lucille Rainbow, Mark R Howard, Shou-Jiang Gao, Roy A Bohenzky, Peter Simmonds, Christine Lee, Annemiek de Ruiter, Angelos Hatzakis, Richard S Tedder, Ian VD Weller, Robin A Weiss, Patrick S Moore
Journal: The Lancet (1996)

Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8, may be the infectious cause of KS. Its prevalence in the general population, on the basis of detection of the virus genome, is controversial. To investigate the seroprevalence, we measured antibodies to a recombinant capsid-related (lytic cycle) KSHV antigen and a latent antigen complex.We selected potentially immunoreactive capsid-related proteins of KSHV by expressing them as recombinant proteins and testing them in western blot assays. We used a truncated recombinant protein encoded by KSHV open reading frame 65 (orf 65) to develop a diagnostic enzyme-linked immunosorbent assay (ELISA) and tested sera from HIV-infected individuals with KS, HIV-uninfected patients with "classic" KS, other HIV risk groups, and blood donors. We also compared the antibody response to this capsid-related protein to the response to latent antigen(s) in an immunofluorescence assay.77/92 (84%) sera from KS patients reacted with the KSHV orf 65 protein and 84/103 (81.5%) reacted with KSHV latent antigen(s). The dominant immunogenic region of orf 65 is within the carboxyterminal 80 aminoacids, a region with little sequence similarity to the related Epstein-Barr virus, suggesting that orf 65 is a KSHV specific antigen. Only three sera from patients with haemophilia (1/84) or from intravenous drug users (2/63) had KSHV specific antibodies in the orf 65 assay whereas none of these sera reacted with latent antigen. Antibodies to KSHV were also infrequently found in UK and US blood donors by either assay (UK, 3/174 with orf 65 and 4/150 with latent antigen; US, 6/117 with orf 65 and 0/117 with latent antigen). They were more common among HIV-infected gay men without KS (5/16 by orf 65 ELISA, 10/33 by IFA), HIV-uninfected STD clinic attenders (14/166 by IFA), and Ugandan HIV-uninfected controls (6/17 by orf 65 ELISA, 9/17 by IFA). Antibody reactivity to the orf 65 protein (ELISA) and to latent antigen(s) (IFA) was concordant in 89% of 462 sera tested but reactive blood donor sera were discordant in both assays. Four AIDS-KS sera were unreactive in both assays.The distribution of antibodies to both a capsid-related recombinant protein and latent antigen(s) of KSHV strongly supports the view that infection with this virus is largely confined to individuals with, or at increased risk for, KS. However, infection with KSHV does occur, rarely, in the general UK and US population and is more common in Uganda. Antibodies to latent antigen(s) or to orf 65 encoded capsid protein will not detect all cases of KSHV infection, and a combination of several antigens will probably be required for accurate screening and confirmatory assays.
A worthy introduction
Authors: Mohsin Ali
Journal: The Lancet Infectious Diseases (2015)

50 years ago, many doctors had consigned infectious diseases to the past. This view—held before the emergence of pathogens such as HIV and the Ebola virus—has often been cited for its hubris. Infectious Disease: A Very Short Introduction begins likewise. "They thought their arsenal of vaccines for preventing viral diseases and broad-spectrum antibiotics for treating bacterial infections could handle any threat", write biologists Marta L Wayne and Benjamin Bolker. "But [infectious] disease was never dead, or even in remission."