tbuckley/cabot-search huggingface dataset:
Severe Alkalosis During Assisted Ventilation in Chronic Obstructive Pulmonary Disease
Authors: Robert Matz
Journal: JAMA (1990)

<h3>To the Editor.—</h3> The excellent review by Drs Schmidt and Hall<sup>1</sup>only briefly touches on a problem that I feel requires greater attention when caring for patients with chronic obstructive pulmonary disease who are receiving ventilatory assistance. That is severe alkalosis, which develops not only owing to hyperventilation in these carbon dioxide retainers but also secondary to an increase in the "strong ion difference" (often called "an increase in bicarbonate or base excess") and to a decrease in the concentration of nonvolatile weak acids.<sup>2-4</sup>The strong ion difference is the difference between the sum of the concentrations of all of the strong cations (Na<sup>+</sup>, K<sup>+</sup>, Ca, and Mg) and the strong anions (Cl<sup>-</sup>, SO<sub>4</sub><sup>=</sup>, and organic acids) and is normally approximately + 42 mEq/L. The nonvolatile weak acids are largely composed of the plasma proteins, with a very minor contribution from inorganic phosphate. The increase in strong ion
Band-shaped and whorled microcystic dystrophy of the corneal epithelium
Authors: Norman C Charles, Joshua A Young, Asok Kumar, Hans E Grossniklaus, David A Palay, Jemison Bowers, W.Richard Green
Journal: Ophthalmology (2000)

ObjectiveTo report the clinical, histopathologic, and electron microscopic features of band-shaped and whorled microcystic corneal epithelial dystrophy.DesignTwo interventional case reports.ParticipantsTwo patients, two eyes.InterventionThe involved area of corneal epithelium was scraped from each cornea.ResultsHistopathologic examination showed microscopic vacuoles in the epithelial cytoplasm in both cases. Electron microscopic examination revealed mainly empty cytoplasmic vacuoles with scant nonspecific osmophilic material. The process recurred clinically in one patient. Changes in corneal topography are documented in one patient.ConclusionClinical findings and pathologic studies seem nearly identical to those in the original report. No pattern of systemic disorder or medication use was found. The cause of this condition remains unknown.
Identifying Suicidal Ideation in General Medical Patients
Authors: Lisa Cooper-Patrick
Journal: JAMA (1994)

<h3>Objectives.</h3> —To describe characteristics of general medical patients with suicidal ideation and to develop an efficient clinical strategy for identifying these patients. <h3>Design.</h3> —Cross-sectional analysis of data without intervention. <h3>Setting.</h3> —A representative sample of community respondents interviewed as part of the National Institute of Mental Health Epidemiologic Catchment Area surveys. <h3>Subjects.</h3> —A total of 6041 individuals who reported receiving care in general medical settings in the 6 months preceding the baseline interview. <h3>Main Outcome Measure.</h3> —Suicidal ideation within the year preceding the baseline interview. <h3>Results.</h3> —A total of 154 patients (2.6%) had experienced suicidal thoughts within the previous year. In multivariate analyses, the following sociodemographic factors were significantly associated with having suicidal ideation: being white (odds ratio [OR], 2.8;<i>P</i>&lt;.001) relative to African American, separated or divorced (OR, 1.8;<i>P</i>=.03) relative to married, and aged 18 to 30 years (OR, 2.3;<i>P</i>=.02) or aged 31 to 50 years (OR, 2.1;<i>P</i>=.03) relative to those older than 65 years. Gender, educational level, and socioeconomic status were not statistically associated with suicidal ideation. Psychiatric disorders significantly associated with suicidal ideation were major depression (OR, 10.3;<i>P</i>&lt;.001), panic disorder (OR, 5.2;<i>P</i>&lt;.001), alcohol disorder (OR, 2.0;<i>P</i>=.04), and phobic disorder (OR, 1.6;<i>P</i>=.02) within the previous year. However, only 34% of respondents with suicidal ideation met criteria for major depression. With the aid of stepwise logistic regression, a four-item screening questionnaire, the Suicidal Ideation Screening Questionnaire, was developed to predict patients with suicidal ideation. Likelihood ratios for suicidal ideation increased from 0.21 to 32.8 with more positive responses to questions concerning symptoms of hopelessness, guilt, depressed mood, and sleep disturbances. <h3>Conclusions.</h3> —If the results from the four-item screen are reproduced in a clinical setting, general medical patients with a high likelihood for suicidal ideation may be identified with a brief screening questionnaire. This screen would have greater sensitivity than would be achieved by assessing suicidal ideation only in those patients who meet criteria for a distinct psychiatric disorder. (<i>JAMA</i>. 1994;272:1757-1762)
Update in Asthma 2006
Authors: Wendy C. Moore, Stephen P. Peters
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Asthma-related investigations reported in 2006 ranged from the characterization of clinical asthma and airway obstruction (1–4), to human biologic studies (5, 6) and the use of animal models to better understand pathobiologic mechanisms at a cellular and molecular level (7–19). The concept of “risk” has been featured prominently, with articles identifying factors that increase the risk of developing asthma (20–24) as well as those aimed at identifying risk factors for asthma exacerbations and adverse outcomes (25–29). Studies have continued to explore the utility of noninvasive biomarkers (exhaled nitric oxide, exhaled breath condensate) to identify (30, 31), modify (32), and treat disease while increasing understanding of pathophysiologic mechanisms in asthma (33, 34). Clinical trials have sought to optimize treatment with established asthma drugs (35–37) and to evaluate novel modalities to fill voids in our current armory of asthma medications (38–40). Overall, this year has been an interesting journey, particularly in clinical asthma research, challenging accepted concepts in asthma therapy, and urging clinicians to expand their assessment of patients to identify and modify patient risk in addition to traditional measures of asthma control (41).
Abstract 778: HER2 as therapeutic target for overcoming ATP-binding cassette transporter-mediated chemoresistance in small cell lung cancer
Authors: Toshiyuki Minami, Takashi Kijima, Yasushi Otani, Satoshi Kohmo, Ryo Takahashi, Izumi Nagatomo, Haruhiko Hirata, Mayumi Suzuki, Koji Inoue, Yoshito Takeda, Hiroshi Kida, Isao Tachibana, Atsushi Kumanogoh
Journal: Cancer Research (2012)

Abstract Small Cell Lung Cancer (SCLC) easily acquires multidrug resistance after successful initial therapy. Overexpression of ATP-binding cassette (ABC) transporters is important for the multidrug resistance. Among them, ABCB1 and ABCG2 are known to be upregulated in chemoresistant SCLC. We found that human epidermal growth factor receptor 2 (HER2) expression is also upregulated in chemoresistant SBC-3/ETP, SBC-3/SN-38 and SBC-3/CDDP cells, compared to chemosensitive SBC-3 cells. Lapatinib, a tyrosine kinase inhibitor of HER2, could not suppress proliferation of these HER2-positive SCLC cells, but successfully restored chemosensitivity to etoposide and SN-38 in SBC-3/ETP and SBC-3/SN-38 cells, respectively. The reversal effect of lapatinib was thought to be caused by inhibition of drug efflux-pump functions of ABC transporters, and was producible with a clinically applicable concentration. Moreover, knocking down of HER2 by a small interfering RNA weakened the effect of lapatinib on ABCB1, indicating the involvement of HER2 in the inhibitory mechanisms. Notably, we demonstrated that caveolin-1 and Src play key roles in modulating ABCB1 function via HER2 inactivation. In SBC-3/ETP cells, dephosphorylation of HER2 by lapatinib activates Src and successively leads to increase caveolin-1 phosphorylation. Through this process, caveolin-1 dissociates from HER2 and strengthens association with ABCB1, and finally impairs the pump functions. Furthermore, we demonstrated that treatment by lapatinib in combination with etoposide or irinotecan significantly suppresses the growth of subcutaneous SBC-3/ETP and SBC-3/SN-38 tumors in mice, respectively. Collectively, these results indicate that combination therapy with lapatinib and cytotoxic agents could conquer ABC transporter-mediated chemoresistance in SCLC, especially in HER2-positive cases. 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 778. doi:1538-7445.AM2012-778
Evaluation of Residual Promoter Activity in γ-Retroviral Self-inactivating (SIN) Vectors
Authors: Wenqin Xu, Jill L Russ, Maribeth V Eiden
Journal: Molecular Therapy (2011)

Therapeutic gene delivery mediated by retroviral vectors has the advantage of stable integration into the host genome. A major safety concern for gene delivery achieved by murine leukemia virus (MLV)-based retroviral vectors is the activation of adjacent cellular genes including oncogenes following integration into the host genome. Self-inactivating (SIN) vectors lacking viral enhancers/promoters in their 3′ long terminal repeat (LTR) have been proposed as a means of overcoming this safety concern. However the MLV-based SIN vectors currently used by laboratories to assess insertional mutagenesis, integration site selection, and the potency of transgene expression are not uniform in the composition of their 3′ LTRs. We constructed a series of SIN vectors representative of the currently employed vectors, but lacking an internal promoter. Green fluorescent protein (GFP) was used as a reporter gene. Target cells exposed to these vectors were evaluated for number of integrants and GFP expression at the messenger RNA (mRNA) level and protein level. We found that viral promoter activity in the 3′ LTR is not attenuated in many currently employed SIN vectors. These results suggest that the influence of strong residual promoter activity should be taken into consideration when interpreting experimental results obtained using SIN vectors in gene therapy research. Therapeutic gene delivery mediated by retroviral vectors has the advantage of stable integration into the host genome. A major safety concern for gene delivery achieved by murine leukemia virus (MLV)-based retroviral vectors is the activation of adjacent cellular genes including oncogenes following integration into the host genome. Self-inactivating (SIN) vectors lacking viral enhancers/promoters in their 3′ long terminal repeat (LTR) have been proposed as a means of overcoming this safety concern. However the MLV-based SIN vectors currently used by laboratories to assess insertional mutagenesis, integration site selection, and the potency of transgene expression are not uniform in the composition of their 3′ LTRs. We constructed a series of SIN vectors representative of the currently employed vectors, but lacking an internal promoter. Green fluorescent protein (GFP) was used as a reporter gene. Target cells exposed to these vectors were evaluated for number of integrants and GFP expression at the messenger RNA (mRNA) level and protein level. We found that viral promoter activity in the 3′ LTR is not attenuated in many currently employed SIN vectors. These results suggest that the influence of strong residual promoter activity should be taken into consideration when interpreting experimental results obtained using SIN vectors in gene therapy research.
Children of the Atomic Bomb: An American Physician's Memoir of Nagasaki, Hiroshima, and the Marshall Islands
Authors: George L. Voelz
Journal: JAMA (1996)

Toshiko remembers her experience at 16: I found my older sister hardly recognizable among the dying and the dead.... Her face was swollen and burnt, her body pierced by glass and wood splinters which I pulled out. I had developed a mucousy diarrhea from the first day and was very uncomfortable and tore bits of my clothing to care for my toilet. But I stayed with my sister. The situation in the basement was appalling: the desperate condition of the victims, the overpowering stench of diarrhea, the vomitus, the excrement, and the putrefying wounds, and burns. Wriggling maggots appeared in my burns. Testimonies by innocent children provide powerful descriptions of death and destruction from the atomic bombings of 50 years ago and the aftereffects on the survivors. Dr Yamazaki has woven their message into his interesting autobiographical work. Assigned in 1949 as physician in charge of the US Atomic Bomb
Intestinal metabolism of plasma free fatty acids. Intracellular compartmentation and mechanisms of control.
Authors: A Gangl, R K Ockner
Journal: Journal of Clinical Investigation (1975)

Fatty acid metabolism in intestinal mucosa has been examined primarily in regard to lipid absorption. Since earlier studies suggested intestinal utilization of plasma free fatty acids (FFA), we investigated mucosal metabolism of plasma FFA in rats. Mucosal radioactivity (1 per cent of administered) was maximal 2 min after i.v. [14C]palmitate. Of mucosal 14C, 42 percent was in water-soluble metabolites, including CO2 and ketoacids, 28 percent in phospholipids, and only 16 per cent in triglycerides. The specific activity of mucosal triglyceride fatty acids (TGFA) was 11 times that of serum TGFA, confirming in situ synthesis. Double isotope experiments showed marked differences in the metabolism of fatty acids entering mucosa simultaneously from lumen and plasma. Whereas luminal fatty acids were chiefly esterified to triglyceride, plasma FFA were preferentially oxidized and incorporated into phospholipids. Crypts did not differ from villi, indicating that intestinal metabolism of plasma FFA is related to their site of entry into epithelial cells. Mucosal metabolism of i.v. [14C]palmitate was minimally affected by glucose administration. However, intraduodenal isocaloric ethanol inhibited mucosal oxidation of FFA by 60 per cent, and increased incorporation into triglycerides nearly twofold. During lipid absorption, mucosal uptake of plasma FFA doubled and incorporation into intestinal lymph triglycerides was increased sixfold. These studies demonstrate an intracellular compartmentation of fatty acids in the intestinal epithelium. In contrast to absorbed luminal fatty acids, plasma FFA in the fasting state are both an energy source and a substrate for the synthesis of tissue phospholipid. The fasting contribution of plasma FFA to mucosal and lymph triglyceride is minimal, but it increases during ethanol administration and fat absorption.
A combinatorial F box protein directed pathway controls TRAF adaptor stability to regulate inflammation
Authors: Bill B Chen, Tiffany A Coon, Jennifer R Glasser, Bryan J McVerry, Jing Zhao, Yutong Zhao, Chunbin Zou, Bryon Ellis, Frank C Sciurba, Yingze Zhang, Rama K Mallampalli
Journal: Nature Immunology (2013)
Increase in public spending on health slowed in 2010, as private health spending rose
Authors: M. Limb
Journal: BMJ (2012)

The latest annual rate of increase in UK health expenditure is the lowest for 13 years, new figures from the Office for National Statistics show.

Expenditure on healthcare rose by only 3.1% from 2009 to 2010, from £136.6bn (€168bn; $220bn) to £140.8 billion. This was “considerably lower” than the growth rate from 2008 to 2009 of 8.8%, says the ONS.

Between 1997 and 2010, the period covered by the statistics, the average annual growth in healthcare expenditure was 7.5%.

In 2010 UK …
Where is the body in the mental model for a story?
Authors: Arthur C. Graesser
Journal: Behavioral and Brain Sciences (1997)

Researchers in the field of discourse processing have investigated how mental models are constructed when adults comprehend stories. They have explored the process of encoding various classes of inferences “on-line” when these mental microworlds are constructed during comprehension. This commentary addresses the extent to which these inferences and mental microworlds are “embodied.”
489 Predicting liver disease complications (HCC and cirrhosis) in patients with chronic hepatitis B infection using a risk function model: The R.E.V.E.A.L.-HBV study
Authors: C.-J. Chen, H.A. Yane, U.H. Iloeje, C.-L. Jen, S.-L. You, Y.E. Liaw
Journal: Journal of Hepatology (2006)
Loss of Autophagy Diminishes Pancreatic β Cell Mass and Function with Resultant Hyperglycemia
Authors: Hye Seung Jung, Kun Wook Chung, Jeong Won Kim, Jin Kim, Masaaki Komatsu, Keiji Tanaka, Yen Hoang Nguyen, Tong Mook Kang, Kun-Ho Yoon, Ji-Won Kim, Yeon Taek Jeong, Myoung Sook Han, Moon-Kyu Lee, Kwang-Won Kim, Jaekyoon Shin, Myung-Shik Lee
Journal: Cell Metabolism (2008)
Occupational exposure to polychlorinated biphenyls (PCBs).
Authors: M S Wolff
Journal: Environmental Health Perspectives (1985)

Human occupational exposure to polychlorinated biphenyls (PCBs) with varying chlorine content has been reported by several investigators, using analyses of blood or adipose samples or skin wipes to evaluate levels in the body. The intensity of occupational exposure is related to both duration and intensity of exposure. The qualitative nature of occupational exposure, as well as casual environmental exposure, has been shown to consist of less readily metabolized PCB congeners. The pattern of PCB congeners in human tissues, determined by gas chromatography, may or may not be readily ascribed to specific PCB standard mixtures. The average occupational exposure, as depicted in several studies of blood, plasma or serum concentrations, is approximately 10 to 1000 times that observed in nonoccupationally exposed persons. Currently used methods of PCB quantitation and pattern identification vary widely, with no uniformly administered criteria being applied to characterize human PCB exposure.
Molecular Diversity at 18 Loci in 321 Wild and 92 Domesticate Lines Reveal No Reduction of Nucleotide Diversity during Triticum monococcum (Einkorn) Domestication: Implications for the Origin of Agriculture
Authors: B. Kilian, H. Ozkan, A. Walther, J. Kohl, T. Dagan, F. Salamini, W. Martin
Journal: Molecular Biology and Evolution (2007)

The diploid wheat Triticum monococcum L. (einkorn) was among the first crops domesticated by humans in the Fertile Crescent 10,000 years ago. During the last 5,000 years, it was replaced by tetraploid and hexaploid wheats and largely forgotten by modern breeders. Einkorn germplasm is thus devoid of breeding bottlenecks and has therefore preserved in unfiltered form the full spectrum of genetic variation that was present during its domestication. We investigated haplotype variation among >12 million nucleotides sequenced at 18 loci across 321 wild and 92 domesticate T. monococcum lines. In contrast to previous studies of cereal domestication, we sampled hundreds of wild lines, rather than a few dozen. Unexpectedly, our broad sample of wild lines reveals that wild einkorn underwent a process of natural genetic differentiation, most likely an incipient speciation, prior to domestication. That natural differentiation was previously overlooked within wild einkorn, but it bears heavily upon inferences concerning the domestication process because it brought forth 3 genetically, and to some extent morphologically, distinct wild einkorn races that we designate here as alpha, beta, and gamma. Only one of those natural races, beta, was exploited by humans for domestication. Nucleotide diversity and haplotype diversity in domesticate einkorn is higher than in its wild sister group, the einkorn beta race, indicating that einkorn underwent no reduction of diversity during domestication. This is in contrast to findings from previous studies of domestication history among more intensely bred crop species. Taken together with archaeological findings from the Fertile Crescent, the data indicate that a specific wild einkorn race that arose without human intervention was subjected to multiple independent domestication events.
Proadrenomedullin NH2-terminal 20 peptide inhibits the voltage-gated Ca2+ channel current through a pertussis toxin-sensitive G protein in rat pheochromocytoma-derived PC 12 cells.
Authors: K Takano, N Yamashita, T Fujita
Journal: Journal of Clinical Investigation (1996)

The effect of proadrenomedullin NH2-terminal 20 peptide (PAMP) on the voltage-gated Ca2+ channel current was investigated using the perforated whole-cell clamp technique on NGF-treated PC12 cells. PAMP inhibited the Ba2+ current through N-type Ca2+ channels in a concentration dependent manner. Injection of GDPbetaS into the cell abolished the inhibition while injection of GTPgammaS into the cell made the inhibition irreversible, indicating that the PAMP-induced inhibition of the voltage-gated Ca2+ channel was mediated by a G protein. The inhibition was abolished by pretreating the cells with pertussis toxin, indicating that a pertussis toxin-sensitive G protein was involved in the signal transduction mechanism of PAMP. The present study revealed that the inhibition of catecholamine secretion from sympathetic nerve endings by PAMP could be explained by the inhibition of N-type Ca2+ channels, which was mediated by pertussis toxin-sensitive G protein.
Changes in in vitro myocardial hydration and performance in response to transient metabolic blockade in hypertonic, isotonic, and hypotonic media
Authors: M. B. PINE, O. H. L. BING, W. W. BROOKS, W. H. ABELMANN
Journal: Cardiovascular Research (1978)

The effect of changes in tonicity of the bathing media on in vitro myocardial water content and mechanical performance during hypoxia and total metabolic blockade (consisting of hypoxia plus glycolytic blockade) was studied in 175 isometrically contracting rat papillary muscles. Recovery of mechanical performance after metabolic blockade in hypertonic (440 mOsm), isotonic (315 mOsm), and hypotonic (190 mOsm) media was also evaluated. Myocardial water contents were 3.2 ± 0.1 cm3·g−1 dry weight in hypertonic, 3.9 ± 0.1 cm3·g−1 in isotonic and 4.5 ± 0.1 cm3·g−1 in hypotonic media. The addition of metabolic blockade did not alter myocardial water content. Return to isotonic solution resulted in restoration of 'normal' myocardial water content both with and without continued metabolic blockade. Developed tension fell during hypoxia in all three media, and recovered partially with reoxygenation and return to isotonic solution. Recovery was best after hypoxia in an isotonic medium and poorest after hypoxia in a hypertonic medium. Tension development was completely lost after less than 15 min of total metabolic blockade and remained absent after removal of glycolytic blockade and reoxygenation regardless of the tonicity of the bathing solution. Thus, appropriate fluid shifts between myocardium and bathing solution in response to alterations in the tonicity of the bath were observed despite total irreversible loss of tension development. In addition, the data do not support the concept that hypertonic solutions protect the myocardium during metabolic blockade.
Intravenous Regional Anesthesia of the Upper Extremity in Children
Authors: Ted F. Gingrich
Journal: JAMA (1967)

One of the more perplexing problems facing the anesthesiologist is provision of adequate and safe anesthesia for young children who have suffered fractures or large lacerations of the hand and forearm. Most children who receive general anesthesia for major suturing or closed reduction of fractures require hospital admission for at least 8 to 24 hours. This communication is a report of a safe and effective method of handling these procedures on an outpatient basis. A 7-year-old girl, weighing 20 kg (44 lb), was admitted to the operating room from the emergency room for full-thickness free skin graft to the left middle finger from which the tip had been avulsed. She had eaten a large evening meal shortly before the injury was sustained. Though moderately apprehensive, she quickly agreed to "just one needle stick" for anesthesia. Two narrow inflatable tourniquets were placed on the upper arm. A 25-gauge scalp vein needle