tbuckley/cabot-search huggingface dataset:
Immature granulocyte fraction in the peripheral blood is a practical indicator for mobilization of CD34<sup>+</sup> cells
Authors: Mari Endo‐Matsubara, Seishi Ogawa, Ko Sasaki, Tsuyoshi Takahashi, Shigeru Chiba, Hisamaru Hirai
Journal: American Journal of Hematology (2004)

Abstract We propose a simple parameter that improves prediction of the number of CD34 + cells in blood cells collected by apheresis for autologous peripheral blood stem cell (PBSC) transplantation following administration of granulocyte colony‐stimulating factor. The percentage of immature granulocytes including myeloblasts, promyelocytes, myelocytes, and metamyelocytes (LSI for left‐shift index) immediately prior to the start of each apheresis correlated with the number of CD34 + cells in PBSC collections ( r = 0.79, P &lt; 0.0001, Y = 0.227 X − 0.99, R 2 = 0.623) much better than did the white blood cell count ( r = 0.07), currently the most commonly used predictor in deciding the initiation of apheresis. We then used receiver operating characteristic (ROC) curves to determine a cutoff point for LSI to prevent unnecessary apheresis. At LSI &gt; 7.5, sensitivity and specificity of cutoff points in the probability of obtaining &gt;1.0 × 10 6 CD34 + cells/kg BW were 93.3% and 94.3% (95% CI, 91.4–100.0%), respectively. When LSI reaches 15.25, nearly 100% of apheresis will attain the target CD34 + cell dose. These findings indicate that LSI is a useful and simple method for predicting the yield of CD34 + cells before the start of PBSC collection and avoiding unnecessary apheresis. Am. J. Hematol. 77:223–228, 2004. © 2004 Wiley‐Liss, Inc.
Prevalence of asthma, allergic rhinoconjunctivitis and allergic sensitization in Mongolia
Authors: A. Viinanen, S. Munhbayarlah, T. Zevgee, L. Narantsetseg, Ts. Naidansuren, M. Koskenvuo, H. Helenius, E. O. Terho
Journal: Allergy (2005)

Background: Studies in countries, such as Mongolia, which are in transition from farming to industrial society permit evaluation of the impact of environmental change on atopic diseases. Methods: In the screening study, questionnaire data were obtained from 9453 subjects aged 10–60 years. In the clinical study, a subsample of 869 subjects (participation rate 50.0%) was examined. A questionnaire‐based interview, clinical examination, skin prick tests, spirometry and bronchodilation test or methacholine challenge test were used to define the clinical diagnoses. The prevalences of atopic diseases were evaluated at the population level using two‐phase data and sampling weights. Results: The prevalences of asthma, allergic rhinoconjunctivitis and allergic sensitization with 95% confidence intervals were 1.1% (0.3–2.0%), 9.3% (4.0–14.6%) and 13.6% (7.4–19.9%) in Mongolian villages, 2.4% (1.4–3.5%), 12.9% (8.2–17.7%) and 25.3% (17.1–33.6%) in rural towns and 2.1% (1.3–3.0%), 18.4% (13.3–23.4%) and 31.0% (24.5–37.5%) in Ulaanbaatar city, respectively. The prevalence of allergic rhinoconjunctivitis ( P = 0.02) and allergic sensitization ( P = 0.003) increased significantly with increasing urbanization. Conclusions: The prevalences of atopic diseases were low in rural Mongolia and increased with increasing urbanization suggesting that rural living environment protects against atopy.
Socioeconomic Status and Risk for Substandard Medical Care
Authors: H R Burstin, S R Lipsitz, T A Brennan
Journal: JAMA (1992)

To assess whether the socioeconomic status of the patient was associated with the risk of adverse events, defined as medical injuries caused by medical management, and the proportion of these events that resulted from substandard care.51 hospitals in New York State.Rates of medical injury and substandard care by gender, race, income, and payer status were developed from reviews of 30,195 medical records in New York in 1984. We evaluated these socioeconomic parameters in a multivariate analysis, while controlling for hospital-level factors.We found that uninsured patients (odds ratio, 2.35; 95% confidence interval, 1.40 to 3.95) were at greater risk for substandard care. The characteristics of the hospitals to which patients were admitted did not affect this result. Race, gender, and income were not independently associated with risk for medical injury or substandard care in multivariate analyses.Our findings suggest that the uninsured are at greater risk for suffering medical injury due to substandard medical care.
Subcutaneous adrenaline versus terbutaline in the treatment of acute severe asthma.
Authors: M A Spiteri, A B Millar, D Pavia, S W Clarke
Journal: Thorax (1988)

Subcutaneous adrenaline and terbutaline have been compared in a double blind study of 20 patients with acute severe asthma presenting to an accident and emergency department. Ten patients received adrenaline 0.5 mg (0.5 ml) and 10 terbutaline 0.5 mg (0.5 ml) subcutaneously. Further treatment with nebulised salbutamol (5 mg), hydrocortisone (200 mg), and aminophylline (0.9 mg/kg/hour) was started 15 minutes later. All patients reported a reduction in chest tightness within three minutes of receiving both adrenaline and terbutaline and reported no adverse effects. Mean baseline values of peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) did not differ significantly between the adrenaline group (130 1 min-1 and 0.83 l) and the terbutaline group (111 1 min-1 and 0.63 l). After administration of adrenaline PEF had increased by 21% and FEV1 by 40% five minutes after the injection, and by 35% and 64% at 15 minutes. Terbutaline caused a 23% increase in PEF and a 37% increase in FEV1 at five minutes, and a 40% and 58% increase at 15 minutes. There was no significant difference in PEF, FEV1, heart rate, blood pressure, or pulsus paradoxus between the two groups at any time. Continuous electrocardiographic recording showed no abnormalities in either group. Thus in this study subcutaneous adrenaline (0.5 mg) and terbutaline (0.5 mg) produced effective rapid bronchodilatation without serious side effects.
Long-term prognostic significance of response in multiple myeloma after stem cell transplantation
Authors: Joaquin Martinez-Lopez, Joan Blade, María-Victoria Mateos, Carlos Grande, Adrián Alegre, José García-Laraña, Anna Sureda, Javier de la Rubia, Eulogio Conde, Rafael Martinez, Felipe de Arriba, Maria C. Viguria, Joan Besalduch, Rafael Cabrera, José D. Gonzalez-San Miguel, José Luis Guzman-Zamudio, Maria Carmen Gomez del Castillo, José Maria Moraleda, Juan C. García-Ruiz, Jesús San Miguel, Juan José Lahuerta
Journal: Blood (2011)
CHEMOPATHOLOGICAL STUDIES WITH COMPOUNDS OF ARSENIC
Authors: Wade H. Brown, Louise Pearce
Journal: The Journal of Experimental Medicine (1915)

1. Toxic doses of all arsenicals of which we have any knowledge produce definite pathological changes in the adrenals of guinea pigs. These changes include congestion, hemorrhage, disturbances in the lipoid content, cellular degenerations and necroses, and reduction in the chromaffin content. 2. The character and severity of the injury produced by different arsenicals varies with the chemical constitution of the compounds. 3. From these facts, we believe that adrenal injury is an important factor in arsenical intoxication and suggest that therapeutic doses of some arsenicals may produce adrenal stimulation.
Book Review Handbook of Occupational Dermatology Edited by L. Kanerva, P. Elsner, J.E. Wahlberg, and H.I. Maibach. 1300 pp., illustrated. New York, Springer-Verlag, 2000. $295. 3-540-64046-0
Authors: Ernesto Gonzalez
Journal: New England Journal of Medicine (2000)
Commons debates NHS morale
Authors: L. Beecham
Journal: BMJ (1996)

For the second time in seven days the House of Commons has debated the health service, this time on a Labour motion alleging a growing demoralisation of NHS staff. This is attributed to changes detrimental to patient care; staff spending more time on paperwork and less time with patients; more managers but fewer beds and nurses; chief executives' pay rises twice those …
Pseudonormal Position of an Atrial Pacemaker Lead Associated With a Contralateral Pneumothorax
Authors: Hirotaka Yada, Toshiaki Sato, Kyoko Soejima, Yusuke Jo, Masahiro Jinzaki, Ikuko Togashi, Hikaru Nakamizo, Kotaro Fukumoto, Kojiro Tanimoto, Shunichiro Miyoshi, Sachio Kuribayashi, Satoshi Ogawa
Journal: Circulation (2008)
Abstract P2-09-17: Allosteric inhibitors of the proteasome: A new concept for breast cancer treatment
Authors: PA Osmulski, M Gaczynska
Journal: Cancer Research (2013)

Abstract Proteasome is an essential protease of the proteasome-ubiquitin pathway, responsible for maintaining intracellular proteostasis. It is a multifunctional, multisubunit enzyme built from interchangeable modules and intricately regulated on the molecular and cellular levels. Proteasome inhibitors display proapoptotic properties, preferentially aimed at cancerous cells. Consequently, targeted therapy with bortezomib, the competitive inhibitor of the proteasome, has been very successful with refractory/relapsed multiple myeloma and with lymphomas. Unfortunately, breast cancers performed disappointingly in clinical trials with bortezomib. We propose that a new generation of small-molecule proteasome inhibitors distinct from bortezomib may prove successful with breast cancers. In contrast to bortezomib which directly blocks proteasome active sites, the new inhibitors are allosteric ligands binding to noncatalytic sites and disrupting the enzyme's function by targeting long-distance transfer of structural signals within the enzyme's molecule. The advantages of allosteric ligands, now rapidly gaining popularity in targeted drug design, include versatility of molecular actions, defying drug resistance mechanisms, and usually high specificity with low toxicity. For example, one of the small-molecule allosteric ligands we created compromises interactions between the catalytic core proteasome and its regulatory sub-assembly 19S (“cap”, regulatory particle) responsible for recognizing and processing the majority of intracellular protein substrates tagged for degradation by polyubiquitin. We found that treatment with nanomolar concentration of the compound induced cell death in Mcf7 human breast cancer cultured cells. Interestingly, this cell line is known for its resistance to bortezomib treatment. Even more, treatment with the allosteric ligand together with bortezomib produced a synergistic effect and sensitized the Mcf7 cells to the actions of competitive inhibitor. Remarkable, the cytotoxic effects of allosteric ligand or its combination with bortezomib were not observed with the noncancerous human breast cell line, Mcf10A. Summarizing, allosteric regulation of the proteasome by small-molecule ligands, alone or in combination with established drugs competitively inhibiting proteasome, seem to be a promising strategy to utilize proteasome as a drug target in breast cancers. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-09-17.
Acute Purulent Otitis Media in Children Older Than 5 Years
Authors: Richard Schwartz
Journal: JAMA (1977)

It is generally believed that<i>Haemophilus influenzae</i>is not commonly a causative agent of otitis media in children older than 5 years of age. We recently studied cases of 58 children, aged from 5 to 9 years, who had acute otitis media.<i>Haemophilus species</i>were the causative agents in 36% of cases. This high incidence of<i>Haemophilus isolation</i>from the middle ear exudate of these children has important therapeutic implications; antibiotics effective against<i>H influenzae</i>should be employed when dealing with otitis media in this older age group. (<i>JAMA</i>238:1032-1033, 1977)
The Effects of Components of Fine Particulate Air Pollution on Mortality in California: Results from CALFINE
Authors: Bart Ostro, Wen-Ying Feng, Rachel Broadwin, Shelley Green, Michael Lipsett
Journal: Environmental Health Perspectives (2006)

Several epidemiologic studies provide evidence of an association between daily mortality and particulate matter < 2.5 pm in diameter (PM2.5). Little is known, however, about the relative effects of PM2.5 constituents. We examined associations between 19 PM2.5 components and daily mortality in six California counties.We obtained daily data from 2000 to 2003 on mortality and PM2.5 mass and components, including elemental and organic carbon (EC and OC), nitrates, sulfates, and various metals. We examined associations of PM2.5 and its constituents with daily counts of several mortality categories: all-cause, cardiovascular, respiratory, and mortality age > 65 years. Poisson regressions incorporating natural splines were used to control for time-varying covariates. Effect estimates were determined for each component in each county and then combined using a random-effects model.PM2.5 mass and several constituents were associated with multiple mortality categories, especially cardiovascular deaths. For example, for a 3-day lag, the latter increased by 1.6, 2.1, 1.6, and 1.5% for PM2.5, EC, OC, and nitrates based on interquartile ranges of 14.6, 0.8, 4.6, and 5.5 pg/m(3), respectively. Stronger associations were observed between mortality and additional pollutants, including sulfates and several metals, during the cool season.This multicounty analysis adds to the growing body of evidence linking PM2.5 with mortality and indicates that excess risks may vary among specific PM2.5 components. Therefore, the use of regression coefficients based on PM2.5 mass may underestimate associations with some PM2.5 components. Also, our findings support the hypothesis that combustion-associated pollutants are particularly important in California.
Medical Hygroscope with Thermometer.
Authors: Henry Emerson Wetherill
Journal: JAMA (1902)

The neck was of a deep brownish-black tint, mottled with little islands of paler hue.The face was Horid and somewhat bronzed, but not definitely melasmic.Eight years ago Mr. Hutchinson prescribed for the patient, who was suffering from lupus erythematosus, 4 minims of liquor arsenicalis three times a day.When Mr. Hutchinson saw the patient again two years later he advised her to discontinue the arsenic, as
Interleukin-7 and infection itself by human immunodeficiency virus 1 favor virus persistence in mature CD4+CD8−CD3+ thymocytes through sustained induction of Bcl-2
Authors: Eric Guillemard, Marie-Thérèse Nugeyre, Laurent Chêne, Nathalie Schmitt, Catherine Jacquemot, Françoise Barré-Sinoussi, Nicole Israël
Journal: Blood (2001)
High-Throughput Screening for <i>Salmonella</i> Avirulent Mutants That Retain Targeting of Solid Tumors
Authors: Nabil Arrach, Pui Cheng, Ming Zhao, Carlos A. Santiviago, Robert M. Hoffman, Michael McClelland
Journal: Cancer Research (2010)

Abstract Salmonella has a natural ability to target a wide range of tumors in animal models. However, strains used for cancer therapy have generally been selected only for their avirulence rather than their tumor-targeting ability. To select Salmonella strains that are avirulent and yet efficient in tumor targeting, a necessary criterion for clinical applications, we measured the relative fitness of 41,000 Salmonella transposon insertion mutants growing in mouse models of human prostate and breast cancer. Two classes of potentially safe mutants were identified. Class 1 mutants showed reduced fitness in normal tissues and unchanged fitness in tumors (e.g., mutants in htrA, SPI-2, and STM3120). Class 2 mutants showed reduced fitness in tumors and normal tissues (e.g., mutants in aroA and aroD). In a competitive fitness assay in human PC-3 tumors growing in mice, class 1 mutant STM3120 had a fitness advantage over class 2 mutants aroA and aroD, validating the findings of the initial screening of a large pool of transposon mutants and indicating a potential advantage of class 1 mutants for delivery of cancer therapeutics. In addition, an STM3120 mutant successfully targeted tumors after intragastric delivery, opening up the oral route as an option for therapy administration. Cancer Res; 70(6); 2165–70
Abstract LB-369: Coxsackievirus B3 is an immunostimulatory oncolytic virus active against lung adenocarcinoma
Authors: Shohei Miyamoto, Hiroyuki Inoue, Beibei Wang, Keisuke Yasunari, Takafumi Nakamura, Meiko Yamada, Yasuo Urata, Tomotoshi Marumoto, Atsushi Takahashi, Koichi Takayama, Yoichi Nakanishi, Hiroyuki Shimizu, Kenzaburo Tani
Journal: Cancer Research (2012)

Abstract Although oncolytic virotherapy is a promising anticancer therapy, antitumor efficacies are hampered by low tumor selectivity. To identify a potent and selective oncolytic virus, we performed large-scale two-step screening of 28 enteroviral strains and found that coxsackievirus B3 (CVB3) possessed specific oncolytic activity against nine human non-small cell lung cancer (NSCLC) cell lines. CVB3-mediated cytotoxicity was positively correlated with the expression of viral receptors, CAR and DAF, on NSCLC cells, and attenuated by loss of CAR expression by siRNA transfection on NSCLC cells. In vitro assays revealed that CVB3 induced apoptosis and PI3K/Akt and MEK/ERK survival signaling pathways, leading to cytotoxicity and regulation of CVB3 replication. Intratumoral injections of CVB3 elicited remarkable regression of pre-established tumors in vivo. Furthermore, administration of CVB3 into xenografts on the right flank resulted in significantly durable regression of uninjected xenografts on the left flank, where replication-competent CVB3 was detected. All treatments with CVB3 were well-tolerated without treatment-related deaths. In addition, intratumoral CVB3 administration markedly recruited NK cells and granulocytes, both of which expressed cytolytic degranulation marker CD107a and contributed to the antitumor effects as demonstrated by depletion assays, macrophages, and mature dendritic cells (DCs) into tumor tissues. Furthermore, we found that CVB3 infection induced abundant calreticulin (CRT) exposure, known as a major checkpoint of immunogenic cell death, on the cell surface of NSCLC cells, as well as extranuclear high mobility group box 1 (HMGB1) translocation from the nuclei to the cytosol in NSCLC cells. Altogether, our findings suggest that CVB3 is a potent and well-tolerated oncolytic agent with immunostimulatory properties active against both localized and metastatic NSCLC and may yield a unique and more effective antitumor activity. 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 LB-369. doi:1538-7445.AM2012-LB-369
The effect of inhaled FK224, a tachykinin NK-1 and NK-2 receptor antagonist, on neurokinin A-induced bronchoconstriction in asthmatics.
Authors: G F Joos, J Van Schoor, J C Kips, R A Pauwels
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The tachykinins substance P and neurokinin A (NKA) are present in sensory airway nerves and have been implicated in the pathogenesis of asthma. FK224 is a cyclopeptide tachykinin antagonist previously shown to inhibit both tachykinin NK-1 and NK-2 receptor mediated airway responses in guinea pigs. Inhaled FK224 protected against bradykinin-induced bronchoconstriction and cough in asthmatics. In this study we examined the reproducibility of the NKA challenge and the effect of inhaled FK224 on NKA-induced bronchoconstriction in 10 patients with stable asthma. On Day 1 baseline lung function and PC20 methacholine were determined. On Days 2 and 3 increasing doubling concentrations of NKA (3.3 x 10(-9) to 1.0 x 10(-6) mol/ml) were administered via inhalation, with intervals of 10 min. On both days NKA caused a concentration-dependent decrease in specific airways conductance (sGaw) and FEV1. Mean +/- SEM, log PC35, sGaw NKA (mol/ml) was -6.61 +/- 0.10 on Day 2 and -6.57 +/- 0.14 on Day 3 (not significant [NS]). On Days 4 and 5 FK224 (4 mg) or placebo (P) was administered via metered-dose inhaler 30 min before NKA challenge in a double-blind, crossover manner. The study medication was well tolerated. FK224 had no significant effect on baseline lung function. After P and FK224, NKA caused a comparable concentration-dependent bronchoconstriction. The mean +/- SEM log PC35 sGaw NKA (mol/ml) was -6.04 +/- 0.18 after P and -6.19 +/- 0.23 after FK224 (NS). In conclusion, inhaled FK224 had no effect on baseline lung function and offered no protection against NKA-induced bronchoconstriction in a group of mild asthmatic patients.
Abstract 4036: Chromosomal amplification of LRRK2 is required for oncogenic MET signaling in papillary renal and thyroid carcinomas
Authors: Brendan D. Looyenga, Kyle A. Furge, Karl J. Dykema, Julie Koeman, Pamela J. Swiatek, Thomas J. Giordano, Andrew B. West, James H. Resau, Bin T. Teh, Jeffrey P. MacKeigan
Journal: Cancer Research (2011)

Abstract The receptor tyrosine kinase MET is frequently amplified in human tumors, resulting in high cell surface densities and constitutive activation even in the absence of growth factor stimulation by its endogenous ligand, HGF. We sought to identify mechanisms of signaling crosstalk that promote MET activation by searching for kinases that are coordinately dysregulated with wild-type MET in human tumors. Bioinformatic analysis identified leucine-rich repeat kinase-2 (LRRK2), which is amplified and overexpressed in papillary renal and thyroid carcinomas. Downregulation of LRRK2 in cultured tumor cells compromises MET activation and selectively impairs MET signaling to mTOR and STAT3. Loss of these critical mitogenic pathways induces cell cycle arrest and cell death concomitant with loss of ATP production and induction of autophagy. Interestingly, knockdown of LRRK2 precisely phenocopies treatment of tumor cells with the endocytic inhibitor chlorpromazine, suggesting that LRRK2 is required for efficient internalization or post-endocytic trafficking of activated MET receptors. We propose that coordinate amplification of LRRK2 and MET functions to promote endosomal signal transduction by MET, which is required for transformation in papillary renal and thyroid cancers. 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 4036. doi:10.1158/1538-7445.AM2011-4036
Local Anesthesia for Neonatal Circumcision
Authors: Howard J. Stang, Megan R. Gunnar, Leonard Snellman, Lawrence M. Condon, Roberta Kestenbaum
Journal: JAMA (1988)

A controlled, double-blind investigation was conducted to determine whether the dorsal penile nerve block using lidocaine hydrochloride without epinephrine would effectively reduce behavioral distress and adrenocortical responses to routine neonatal circumcision. The subjects were healthy male newborns whose parents had requested circumcision. Equal numbers (n=20) were randomly assigned to circumcision with lidocaine, saline, or no injection. Dorsal penile nerve block was found to be a safe and easy technique that was effective in reducing behavioral distress and modifying the adrenocortical stress response. The injection itself did not increase stress reactions and did not offset the beneficial effects of anesthesia. If circumcisions are to be performed, they should be done as humanely as possible. (<i>JAMA</i>1988;259:1507-1511)
EFFECT OF INTRINSIC QRS MORPHOLOGY ON LONG-TERM RESULT IN RESPONSE TO CARDIAC RESYNCHRONIZATION THERAPY
Authors: Koichi Inoue, Koji Tanaka, Yuko Toyoshima, Nobuaki Tanaka, Takafumi Oka, Yohei Sotomi, Yoichi Nozato, Takaaki Isshiki, T. Kimura, M. Nobuyoshi, Kenji Ando, S. Shizuta, Takeshi Arita, S. Fujii, Katsuomi Iwakura, Kenshi Fujii
Journal: Journal of the American College of Cardiology (2014)