tbuckley/cabot-search huggingface dataset:
Quality of Care Review: Some Progress, and Toward What Goal?
Authors: David Z.J. Chu
Journal: Journal of Clinical Oncology (2009)

TO THE EDITOR: Drs Lorenz and Ganz brought together a stellar group of investigators providing a comprehensive review on quality of care and supportive care in oncology. I commend the authors for stating up front that an examination of quality of care in oncology needs to include not only the supportive and end-of-life aspects, but also the entire spectrum of clinical care. However, having emphasized the multidisciplinary aspects of palliative care, the authors failed to review the progress of supportive care in surgical and radiologic treatments of the cancer patient. One of the most important contributions of health-related quality-of-life research to clinical care is the inclusion of patient and family input into the decision-making process for the treatment of cancer. Whether the decision is to proceed with a major curative operation or embark on several months of systemic chemotherapy, the decision-making process has largely been based on survival and morbidity-mortality rates, performance status, molecular markers, and other clinical end points. The patient may be provided with a detailed explanation of the scientific basis of the treatment options. However, patient and family involvement in the decision-making process has been peripheral. Today, the patient can choose among several treatment options resulting in better quality of life, and sometimes not take advantage of the curative potential of other, more disabling treatment options. For example, neoadjuvant chemotherapy with complete or partial responses can allow organ preservation with minimal compromise in eventual survival rates. The need for additional research in quality of care has been outlined by several authors. In oncologic surgical care, the need for research into quality of care and palliative surgery has been underestimated. Just as quality-of-life measures have been incorporated into several phase III trials, these measures should also be incorporated into newer, minimally invasive surgical treatment evaluations. Lack of awareness and underuse of supportive care services have also been well documented. There is a general consensus about the need to evaluate quality of care. However, there is neither a consensus nor a clinical standard in the measure of quality of care. These measures need to be simple and easily applied at the bedside or clinic. The adopted measure has to be reproducible among different investigators and clinicians across different institutions. The end points from these measures need to be consistent with other clinical standards, and when applied to patient care, the results will indicate improved, cost-effective patient management.
Influence of gender on waking genioglossal electromyogram and upper airway resistance.
Authors: R M Popovic, D P White
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Obstructive sleep apnea is generally recognized as more common in men than in women. This could relate to gender differences in either ventilatory control mechanisms or the structure and function of the pharyngeal airway. Most studies suggest that women have a structurally smaller pharyngeal airway than men, which would likely predispose rather than protect them from airway collapse. However, pharyngeal airway patency is actually a dynamic interaction between anatomy and pharyngeal muscle activity. We therefore hypothesized that females may have increased pharyngeal dilator muscle activity, thereby protecting them from airway collapse during sleep. To test this hypothesis, we compared genioglossal EMG (GG-EMG, measured as a percentage of maximal muscle activity) and upper airway resistance in 22 healthy subjects, 11 males and 11 females, during wakefulness. No significant difference in pharyngeal resistance could be found between the genders. However, inspiratory peak phasic and expiratory tonic GG-EMG activity were both significantly greater in females (GG-EMG peak phasic; 24.3 +/- 3.8 versus 13.1 +/- 4.5% of maximum, p < 0.02; GG-EMG tonic; 12.2 +/- 2.8 versus 4.7 +/- 1.2% of maximum, p < 0.01). In addition, females demonstrated a significant EMG response to inspiratory loading that was not observed in men. We conclude that women have, under basal conditions during wakefulness, augmented genioglossal muscle activity compared with men. To the extent that this augmented muscle activity is maintained across states, the female airway may be more stable and less collapsible.
Stearoyl Co-A Desaturase 1 as a ccRCC Therapeutic Target: Death by Stress
Authors: Janet Y. Leung, William Y. Kim
Journal: Clinical Cancer Research (2013)

There is a need for the discovery of novel therapeutic strategies to effectively treat advanced clear cell renal cell carcinoma (ccRCC). Inhibition of stearoyl-coA desaturase 1 (SCD1) in ccRCC reveals antitumor activity, independently and in synergy with mTOR inhibition. SCD1 may be a potential novel therapeutic target in treating ccRCC.
Synthetic Strands of Neonatal Mouse Cardiac Myocytes
Authors: Stuart P. Thomas, Lilly Bircher-Lehmann, Suma A. Thomas, Jianping Zhuang, Jeffrey E. Saffitz, André G. Kléber
Journal: Circulation Research (2000)

The aim of the present study was to morphologically and electrically characterize synthetic strands of mouse ventricular myocytes. Linear strands of mouse ventricular myocytes with widths of 34.7+/-4.4 microm (W(1)), 57.9+/-2.5 microm (W(2)), and 86.4+/-3. 6 microm (W(3)) and a length of 10 mm were produced on glass coverslips with a photolithographic technique. Action potentials (APs) were measured from individual cells within the strands with cell-attached microelectrodes. Impulse propagation and AP upstrokes were measured with multisite optical mapping (RH237). Immunostaining was performed to assess cell-cell connections and myofibril arrangement with polyclonal antisera against connexin43 and N-cadherins and monoclonal antibodies against cardiac myosin. Light microscopy and myosin staining showed dense growth of well-developed elongated myocytes with lengths of 34.2+/-4.2 microm (W(1)), 36. 9+/-5.8 microm (W(2)), and 43.7+/-6.9 microm (W(3)), and length/width ratios of 3.9+/-0.2. Gap junctions were distributed around the cell borders (3 to 4 junctions/microm(2) cell area). Each cell was connected by gap junctions to 6.5+/-1.1 neighboring cells. AP duration shortened with time in culture (action potential duration at 50% repolarization: day 4, 103+/-34 ms; day 8, 16+/-3 ms; P:<0.01). Minimum diastolic potential and AP amplitude were 71+/-5 and 97.2+/-7.6 mV, respectively. Conduction velocity and the maximum dV/dt of the AP upstroke were 43.9+/-13.6 cm/s and 196+/-67 V/s, respectively. Thus, neonatal ventricular mouse myocytes can be grown in continuous synthetic strands. Gap junction distribution is similar to the neonatal pattern observed in the hearts of larger mammals. Conduction velocity is in the range observed in adult mice and in the higher range for mammalian species probably due to the higher dV/dt(max). This technique will permit the study of propagation, AP, and structure-function relations at cellular resolution in genetically modified mice.
Immunotherapy of tumors with vaccine based on quail homologous vascular endothelial growth factor receptor-2
Authors: Ji-yan Liu, Yu-quan Wei, Li Yang, Xia Zhao, Ling Tian, Jian-mei Hou, Ting Niu, Fen Liu, Yu Jiang, Bing Hu, Yang Wu, Jing-mei Su, Yan-yan Lou, Qiu-ming He, Yan-jun Wen, Jin-liang Yang, Bing Kan, Yong-qiu Mao, Feng Luo, Feng Peng
Journal: Blood (2003)
Relationship between air pollution, lung function and asthma in adolescents
Authors: T. Islam, W J. Gauderman, K. Berhane, R. McConnell, E. Avol, J. M Peters, F. D Gilliland
Journal: Thorax (2007)

<h3>Background:</h3> The interrelationships between air pollution, lung function and the incidence of childhood asthma have yet to be established. A study was undertaken to determine whether lung function is associated with new onset asthma and whether this relationship varies by exposure to ambient air pollutants. <h3>Methods:</h3> A cohort of children aged 9–10 years without asthma or wheeze at study entry were identified from the Children's Health Study and followed for 8 years. The participants resided in 12 communities with a wide range of ambient air pollutants that were measured continuously. Spirometric testing was performed and a medical diagnosis of asthma was ascertained annually. Proportional hazard regression models were fitted to investigate the relationship between lung function at study entry and the subsequent development of asthma and to determine whether air pollutants modify these associations. <h3>Results:</h3> The level of airway flow was associated with new onset asthma. Over the 10th–90th percentile range of forced expiratory flow over the mid-range of expiration (FEF<sub>25–75</sub>, 57.1%), the hazard ratio (HR) of new onset asthma was 0.50 (95% CI 0.35 to 0.71). This protective effect of better lung function was reduced in children exposed to higher levels of particulate matter with an aerodynamic diameter &lt;2.5 μm (PM<sub>2.5</sub>). Over the 10th–90th percentile range of FEF<sub>25–75</sub>, the HR of new onset asthma was 0.34 (95% CI 0.21 to 0.56) in communities with low PM<sub>2.5</sub> (&lt;13.7 μg/m<sup>3</sup>) and 0.76 (95% CI 0.45 to 1.26) in communities with high PM<sub>2.5</sub> (⩾13.7 μg/m<sup>3</sup>). A similar pattern was observed for forced expiratory volume in 1 s. Little variation in HR was observed for ozone. <h3>Conclusion:</h3> Exposure to high levels of PM<sub>2.5</sub> attenuates the protective effect of better lung function against new onset asthma.
Alternative Splicing of Ryanodine Receptors Modulates Cardiomyocyte Ca <sup>2+</sup> Signaling and Susceptibility to Apoptosis
Authors: Christopher H. George, Sarah A. Rogers, Benedicte M.A. Bertrand, Richard E.A. Tunwell, N. Lowri Thomas, Derek S. Steele, Eryl V. Cox, Christopher Pepper, Carolyn J. Hazeel, William C. Claycomb, F. Anthony Lai
Journal: Circulation Research (2007)

Ca(2+) release via type 2 ryanodine receptors (RyR2) regulates cardiac function. Molecular cloning of human RyR2 identified 2 alternatively spliced variants, comprising 30- and 24-bp sequence insertions; yet their role in shaping cardiomyocyte Ca(2+) signaling and cell phenotype is unknown. We profiled the developmental regulation and the tissue and species specificity of these variants and showed that their recombinant expression in HL-1 cardiomyocytes profoundly modulated nuclear and cytoplasmic Ca(2+) release. All splice variants localized to the sarcoplasmic reticulum, perinuclear Golgi apparatus, and to finger-like invaginations of the nuclear envelope (nucleoplasmic reticulum). Strikingly, the 24-bp splice insertion that was present at low levels in embryonic and adult hearts was essential for targeting RyR2 to an intranuclear Golgi apparatus and promoted the intracellular segregation of this variant. The amplitude variability of nuclear and cytoplasmic Ca(2+) fluxes were reduced in nonstimulated cardiomyocytes expressing both 30- and 24-bp splice variants and were associated with lower basal levels of apoptosis. Expression of RyR2 containing the 24-bp insertion also suppressed intracellular Ca(2+) fluxes following prolonged caffeine exposure (1 mmol/L, 16 hours) that protected cells from apoptosis. The antiapoptotic effects of this variant were linked to increased levels of Bcl-2 phosphorylation. In contrast, RyR2 containing the 30-bp insertion, which was abundant in human embryonic heart but was decreased during cardiac development, did not protect cardiomyocytes from caffeine-evoked apoptosis. Thus, we provide the first evidence that RyR2 splice variants exquisitely modulate intracellular Ca(2+) signaling and are key determinants of cardiomyocyte apoptotic susceptibility.
Presurgical Chemotherapy Compared With Immediate Surgery and Adjuvant Chemotherapy for Nonmetastatic Osteosarcoma: Pediatric Oncology Group Study POG-8651
Authors: Allen M. Goorin, Douglas J. Schwartzentruber, Meenakshi Devidas, Mark C. Gebhardt, Alberto G. Ayala, Michael B. Harris, Lee J. Helman, Holcombe E. Grier, Michael P. Link
Journal: Journal of Clinical Oncology (2003)

Purpose: Successful therapeutic interventions to prevent disease progression in patients with nonmetastatic osteosarcoma have included surgery with adjuvant chemotherapy. Presurgical chemotherapy has been advocated for these patients because of putative improvement in event-free survival (EFS). The advantages of presurgical chemotherapy include early administration of systemic chemotherapy, shrinkage of primary tumor, and pathologic identification of risk groups. The theoretic disadvantage is that it exposes a large tumor burden to marginally effective chemotherapy. The contribution of chemotherapy and surgery timing has not been tested rigorously. Patients and Methods: Between 1986 and 1993, we conducted a prospective trial in patients with nonmetastatic osteosarcoma who were assigned randomly to immediate surgery or presurgical chemotherapy. Except for the timing of surgery (week 0 or 10), patients received 44 weeks of identical combination chemotherapy that included high-dose methotrexate with leucovorin rescue, doxorubicin, cisplatin, bleomycin, cyclophosphamide, and dactinomycin. Results: One hundred six patients were enrolled onto this study. Six were excluded from analysis. Of the remaining 100 patients, 45 were randomly assigned to immediate chemotherapy, and 55 were randomly assigned to immediate surgery. Sixty-seven patients remain disease-free. At 5 years, the projected EFS ± SE is 65% ± 6% (69% ± 8% for immediate surgery and 61% ± 8% for presurgical chemotherapy; P = .8). The treatment arms had similar incidence of limb salvage (55% for immediate surgery and 50% for presurgical chemotherapy). Conclusion: Chemotherapy was effective in both treatment groups. There was no advantage in EFS for patients given presurgical chemotherapy.
Letter: Was it a drug? (Optimax).
Authors: J W Barnett
Journal: BMJ (1974)

Some intrauterine devices are easily seen on a plain x-ray.The Dalkon Shield, however, has a lower level of radio-ovacity, and unless certain x-ray techniques are used the device may be difficult or impossible to see.The radio-opacity is achieved by the addition of barium sulphate, which has the undesirable effect of rendering the device more brittle To enable the Dalkon Shield to be bent during insertion through the cervical canal it must be as thin and as pliable as possible, and the concentration of barium sul,phate is therefore kept lower than in other devices.Three techniques for the radiographic location of the Dalkon Shield are suggested for the average-sized patient: (1) "Regular" technique: machine setting 200 mA, 76 kV, 3/5 sec.(2) "Soft-tissue" technique A: machine setting 200 mA, 76 kV, 1/2 sec.(3) "Soft-tissue" technique B: machine setting 200 mA, 70 kV, 2/5-1/2 sec.We would recommend the use of one of the above radiological techniaues should radio- graphic location of a Dalkon Shield be required.-Weare, etc.,
<i>In vivo</i>Antitumor Activity of a Recombinant IL-7/HGFβ Hybrid Cytokine in Mice
Authors: Laijun Lai, Jingjun Jin, Irving Goldschneider
Journal: Cancer Research (2010)

The immune cytokine interleukin (IL)-7 and the β-chain of hepatocyte growth factor (HGF) aggregate to form a naturally occurring heterodimer that stimulates the growth of common lymphoid progenitors and immature B and T lymphoid cells. We have cloned and expressed the heterodimer as a single-chain hybrid cytokine [recombinant (r) IL-7/HGFβ], which stimulates short-term hematopoietic stem cells as well as lymphoid precursors. Inasmuch as IL-7 and HGF are known to have antitumor and protumor activities, respectively, we determined here whether either of these activities is exhibited by rIL-7/HGFβ. We show that the in vivo administration of rIL-7/HGFβ markedly inhibits the growth of newly initiated and established tumors and the formation of pulmonary metastases in murine models of colon cancer and melanoma. The antitumor effect of rIL-7/HGFβ correlated with a marked increase in the number of tumor-infiltrating CD4(+) and CD8(+) T cells and activated dendritic cells. A major role for these immune cells in tumor suppression was indicated by the inability of rIL-7/HGFβ to inhibit the growth of tumor cells in vitro and in congenitally athymic mice. Analysis of interferon-γ-secreting T cells showed that the immune response was tumor specific. Our findings justify further evaluation of rIL-7/HGFβ as a novel experimental cancer therapy.
SIMILARITY OF HOST RESPONSES ELICITED BY POLYSACCHARIDES OF ANIMAL AND PLANT ORIGIN AND BY BACTERIAL ENDOTOXINS
Authors: Maurice Landy, Murray J. Shear
Journal: The Journal of Experimental Medicine (1957)

Ten polysaccharides, isolated from various animal and plant sources, were selected for comparison with 2 bacterial polysaccharides, typical of Gram-negative endotoxins. The tissue sources were: mouse (kidney, liver, lung, stomach, Sarcoma 37, and Carcinoma 241-6); rabbit skin and chick embryo skin; and tangerine and Bryonia root. The bacterial endotoxins were those of S. typhosa and Serr. marcescens. Their relative potency was determined in inducing the following host effects: fever, tolerance to pyrogenic action, leucocytic changes, the Shwartzman reaction, damage to Sarcoma 37, dermal hemorrhagic-necrosis by epinephrine, enhancement of antibody production, and lethality. Some of the polysaccharides were consistently active in all the host reactions studied; except for pyrogenic activity at high dosage, the other polysaccharides were consistently negative throughout. The mouse tissue polysaccharides elicited all the effects studied; in some instances their potency approached those of the bacterial polysaccharides. It is pointed out that elicitation of the above array of biological phenomena, hitherto considered characteristic of bacterial endotoxins, can be obtained with polysaccharides from animal and plant tissues.
Herpes Simplex Virus-2 as a Human Papillomavirus Cofactor in the Etiology of Invasive Cervical Cancer
Authors: J. S. Smith
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Human papillomavirus (HPV) infection is the main cause of invasive cervical cancer, but cofactors may act in conjunction with HPV. We performed a pooled analysis of seven case–control studies to examine the effect of one possible HPV cofactor, herpes simplex virus-2 (HSV-2) infection, in the etiology of invasive cervical cancer. Methods: Blood and exfoliated cervical specimens were obtained from 1263 case patients with invasive cervical cancer (1158 with squamous-cell carcinomas and 105 with adeno- or adenosquamous-cell carcinomas) and 1117 age-matched control subjects. Western blot analysis and/or an enzyme-linked immunosorbent assay were used to detect type-specific serum antibodies to HSV-2 and HSV-1, and Chlamydia trachomatis serum antibodies were detected using a micro-immunofluorescence assay. HPV DNA was detected using a polymerase chain reaction assay. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were computed from unconditional logistic regression models. Results: Overall, HSV-2 seropositivity was higher among case patients with squamous-cell carcinoma (44.4%, 95% CI = 41.5% to 47.3%) or adeno- or adenosquamous-cell carcinoma (43.8%, 95% CI = 34.2% to 53.5%) than among control subjects (25.6%, 95% CI = 23.0% to 28.2%). Cervical specimens from 1098 (94.8%) squamous-cell carcinoma case patients, 95 (90.5%) adeno- or adenosquamous carcinoma case patients, and 164 (14.7%) control subjects were positive for HPV DNA. Among the HPV DNA-positive women, HSV-2 seropositivity was associated with increased risks of squamous-cell carcinoma (OR = 2.19, 95% CI = 1.41 to 3.40) and adeno- or adenosquamous-cell carcinoma (OR = 3.37, 95% CI = 1.47 to 7.74) after adjustment for potential confounders. A similar association between HSV-2 seropositivity and squamous-cell carcinoma risk was observed after further controlling for markers of sexual behavior (OR = 1.96, 95% CI = 1.24 to 3.09). Among control subjects, HSV-2 seropositivity was associated with markers of sexual behavior, but not with cervical HPV DNA positivity. Conclusion: HSV-2 infection may act in conjunction with HPV infection to increase the risk of invasive cervical carcinoma.
STAT6-mediated displacement of polycomb by trithorax complex establishes long-term maintenance of GATA3 expression in T helper type 2 cells
Authors: Atsushi Onodera, Masakatsu Yamashita, Yusuke Endo, Makoto Kuwahara, Soichi Tofukuji, Hiroyuki Hosokawa, Akinori Kanai, Yutaka Suzuki, Toshinori Nakayama
Journal: The Journal of Experimental Medicine (2010)

Polycomb group (PcG) and trithorax group (TrxG) complexes exert opposing effects on the maintenance of the transcriptional status of the developmentally regulated Hox genes. In this study, we show that activation of STAT6 induces displacement of the PcG complex by the TrxG complex at the upstream region of the gene encoding GATA3, a transcription factor essential for T helper type 2 (Th2) cell differentiation. Once Th2 cells differentiate, TrxG complex associated with the TrxG component Menin binds to the whole GATA3 gene locus, and this binding is required for the long-term maintenance of expression of GATA3 and Th2 cytokine. Thus, STAT6-mediated displacement of PcG by the TrxG complex establishes subsequent STAT6-independent maintenance of GATA3 expression in Th2 cells via the recruitment of the Menin-TrxG complex.
AIDS and UK respiratory physicians: attitudes to confidentiality, infection control, and management.
Authors: S Church, S Owen, A A Woodcock
Journal: Thorax (1990)

Respiratory physicians are concerned in the management of most patients with AIDS. Attitudes and practices of 463 respiratory physicians in the United Kingdom in relation to confidentiality, infection control, and treatment were sought by questionnaire from December 1987 to March 1988; 266 replies were received. Thirty eight per cent of respondents had not seen an HIV positive patient at the time of the survey. Respiratory physicians followed General Medical Council guidelines in relation to consent and confidentiality, except that if the patient's consent was withheld three quarters of the physicians would still inform an at risk hospital health care worker; only a quarter, however, would inform an at risk spouse. Routine infection control was frequently inadequate and "disease specific"--that is, substantially increased for known HIV positive patients. Given an HIV positive patient with respiratory symptoms and an abnormal chest radiograph, two thirds of respiratory physicians said that they would treat empirically for Pneumocystis carinii pneumonia as opposed to immediate bronchoscopy for accurate diagnosis. If a patient with AIDS who had pneumocystis pneumonia developed respiratory failure, half the physicians said at that time that they would elect not to ventilate the patient.