tbuckley/cabot-search huggingface dataset:
Effect of Low Phenylalanine Diet on Murine Leukemia L1210 2
Authors: Martin J. Pine
Journal: JNCI Journal of the National Cancer Institute (1978)

Survival of inbred DBA/2 mice or F, hybrids bearing ascites L1210 leukemia or P288 leukemia could be prolonged if phenylalanine (Phe) intake was moderately restricted to 0.08% of the diet. Several lines of evidence indicated that diet acted against L1210 tumors by potentiating host defense rather than by starving tumors directly. Diet lowered the rate of ascites L1210 cell accumulation by 15%. This minor growth inhibition was retained upon host pre irradiation with 100-250 rads, but host protection was abolished. Implanted non immune splenocytes also antagonized dietary protection. Both antagonisms were interpreted in terms of immunosuppression. Adoptive immunity was examined with splenocytes from cured hosts or from mice primed with irradiated L1210 cells. Splenocyte recipients survived L1210 tumor longer when the donor, recipient, or both were fed on limited, ineffective diet schedules. Immune potentiation could thus be produced by diet without direct inhibition of L1210 tumor. In host and tumor subllnes, diet effects correlated with Immunogenlclty. Thus diet was completely curative in (BALB/c♀ x DBA/2HaDD♂)F, hosts with L1210 tumors and optimally doubled survival times of inbred DBA/2HaDD hosts with L1210 tumors; however, it was effective in syngeneic DBA/2 hosts only against the more immunogenic subllne L1210/GZL. Diet was protective even if started after L1210 tumor implantation. Prolongation of host survival was greatly reduced or abolished if, in separate modifications the diet was discontinued, the tyrosine level was lowered additionally to 0.04%, the Phe level was changed to 0 or 0.36%, ammonia lyase was coadministered, or weight losses were matched with restricted chow diet. Serum Phe levels fell below half-normal levels after a week of diet. L1210 eell growth initially faeilitated but later tended to reverse this fall.
Maintenance daily oral etoposide versus no further therapy following induction chemotherapy with etoposide plus ifosfamide plus cisplatin in extensive small-cell lung cancer:a Hoosier Oncology Group randomized study
Authors: N.H. Hanna, A.B. Sandler, P.J. Loehrer, R. Ansari, S.H. Jung, K. Lane, L.H. Einhorn
Journal: Annals of Oncology (2002)

BackgroundWe performed this phase III study to determine whether the addition of 3 months of oral etoposide in non-progressing patients with extensive small-cell lung cancer (SCLC) treated with four cycles of etoposide plus ifosfamide plus cisplatin (VIP) improves progression-free survival (PFS) or overall survival.Patients and methodsPatients with extensive SCLC with a Karnofsky performance score (KPS) ≥50, adequate renal function and bone marrow reserve were eligible. Patients with CNS metastasis were eligible and received concurrent whole-brain radiotherapy. All patients received etoposide75 mg/m2, ifosfamide 1.2 g/m2 and cisplatin 20 mg/m2 intravenously on days 1–4 every 3 weeks for four cycles. Non-progressing patients were randomized to oral etoposide 50 mg/m2 for 21 consecutive days every 4 weeks for three courses versus no further therapy until progression.ResultsFrom September 1993 to June 1998, 233 patients were entered and treated with VIP with 144 non-progressing patients subsequently randomized to oral etoposide (n = 72) or observation (n = 72). Minimum follow up for all patients is 2 years. Toxicity with oral etoposide was mild. There was an improvement in median PFS favoring the maintenance arm of 8.23 versus 6.5 months (P = 0.0018). There was a trend towards an improvement in median (12.2 versus 11.2 months), 1-year (51.4% versus 40.3%), 2-year (16.7% versus 6.9%) and 3-year (9.1% versus 1.9%) survival (P = 0.0704) favoring the maintenance arm.ConclusionsThree months of oral etoposide in non-progressing patients with extensive SCLC was associated with a significant improvement in PFS and a trend towards improved overall survival.
A comparison of four shoulder-specific questionnaires in primary care
Authors: A Paul, M Lewis, M F Shadforth, P R Croft, D A W M Van Der Windt, E M Hay
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objectives:</b> To compare the validity, responsiveness to change, and user friendliness of four self completed, shoulder-specific questionnaires in primary care. <b>Methods:</b> A cross sectional assessment of validity and a longitudinal assessment of responsiveness to change of four shoulder questionnaires was carried out: the Dutch Shoulder Disability Questionnaire (SDQ-NL); the United Kingdom Shoulder Disability Questionnaire (SDQ-UK); and two American instruments, the Shoulder Pain and Disability Index (SPADI) and the Shoulder Rating Questionnaire (SRQ). 180 primary care consulters with new shoulder region pain each completed two of the questionnaires, as well as EuroQoL and 10 cm visual analogue scales (VAS) for overall pain and difficulty due to the shoulder problem. Each participant was assessed by a standardised clinical schedule. Postal follow up at 6 weeks included baseline measures and self rated assessment of global change of the shoulder problem (seven point Likert scale). <b>Results:</b> Strongest correlations were found for SDQ-UK with EuroQoL 5 score, and for SPADI and SRQ with shoulder pain and difficulty VAS. All shoulder questionnaires correlated poorly with active movement at the painful shoulder. SPADI and SRQ performed better on ROC analysis than SDQ-NL and SDQ-UK (areas under the curve of 0.87, 0.85, 0.77, and 0.77, respectively). However, SRQ scores changed significantly over time in stable subjects. <b>Conclusions:</b> Cross sectional comparison of the four shoulder questionnaires showed they had similar overall validity and patient acceptability. SPADI and SRQ were most responsive to change. Additionally, SPADI was the quickest to complete and scores did not change significantly in stable subjects.
Zidovudine (AZT) causes an oxidation of mitochondrial DNA in mouse liver
Authors: José García de la Asunción, María L. del Olmo, Juan Sastre, Federico V. Pallardó, José Viña
Journal: Hepatology (1999)

Zidovudine (3′–azido–2′,3′–dideoxythymidine [AZT]) inhibits human immunodeficiency virus replication and delays progression of acquired immune deficiency syndrome. We have recently found that, in muscle, AZT causes oxidative damage to mitochondrial DNA (mtDNA) and other signs of mitochondrial oxidative damage. The aim of this work was to test if AZT causes oxidative damage to liver mtDNA. In our study, an experimental mouse model was used in which mice were administered AZT (10 mg/kg body weight/d) in drinking water. Liver mtDNA of mice treated with AZT had 40% more of the oxidized, mutagenic nucleoside, 8–oxo–7,8–dihydroxy–2′deoxyguanosine (8–oxo–dG) than untreated controls. This oxidative damage to mtDNA is caused by a significant increase (of over 240%) in peroxide production by liver mitochondria from AZT–treated mice, which was prevented by dietary administration with vitamins C and E.
Magnetic Resonance Imaging of Temperature-Sensitive Liposome Release: Drug Dose Painting and Antitumor Effects
Authors: Ana M. Ponce, Benjamin L. Viglianti, Daohai Yu, Pavel S. Yarmolenko, Charles R. Michelich, Janet Woo, Marcel B. Bally, Mark W. Dewhirst
Journal: JNCI Journal of the National Cancer Institute (2007)

In preclinical studies, lysolipid-based temperature-sensitive liposomes (LTSLs) containing chemotherapy drugs administered in combination with local hyperthermia have been found to increase tumor drug concentrations and improve antitumor efficacy of the drugs. We used a novel magnetic resonance imaging (MRI) method to measure the temporal and spatial patterns of drug delivery in a rat fibrosarcoma model during treatment with LTSLs containing doxorubicin and an MRI contrast agent (manganese) (Dox/Mn-LTSLs) administered at different times with respect to hyperthermia.Rats bearing 10- to 12-mm fibrosarcomas (n = 6-7 per group) were treated with Dox/Mn-LTSLs (at a dose of 5 mg doxorubicin/kg body weight) before and/or during 60 minutes of local tumor hyperthermia administered via a catheter inserted at the center of the tumor. Drug distribution was monitored continuously via MRI. Magnetic resonance changes were used to calculate intratumoral doxorubicin concentrations throughout treatment. Tumors were monitored until they reached five times their volume on the day of treatment or 60 days. Doxorubicin concentrations and times for tumors to reach five times their volume on the day of treatment were analyzed using the Kruskal-Wallis test and the Kaplan-Meier product-limit method, respectively. All statistical tests were two-sided.Administration of Dox/Mn-LTSLs before, during, and both before and during hyperthermia yielded central, peripheral, and uniform drug distributions, respectively. Doxorubicin accumulated more quickly and reached higher concentrations in the tumor when Dox/Mn-LTSLs were administered during hyperthermia than when administered before hyperthermia (rate: 9.8 versus 1.8 microg/min, difference = 8.0 microg/min, 95% confidence interval [CI] = 6.8 to 12.8 microg/min, P = .003; concentration: 15.1 versus 8.0 ng/mg, difference = 7.1 ng/mg, 95% CI = 3.6 to 10.6 ng/mg, P = .028). LTSL administered during hyperthermia also yielded the greatest antitumor effect, with a median time for tumors to reach five times their volume on the day of treatment of 34 days (95% CI = 30 days to infinity) compared with 18.5 days (95% CI = 16 to 23 days) for LTSL before hyperthermia and 22.5 days (95% CI = 15 to 25 days) for LTSL before and during hyperthermia.In this rat fibrosarcoma model, LTSLs were most effective when delivered during hyperthermia, which resulted in a peripheral drug distribution.
Guinea pig transglutaminase immunolinked assay does not predict coeliac disease in patients with chronic liver disease
Authors: A Carroccio
Journal: Gut (2001)

<h3>BACKGROUND</h3> It has been suggested that serological screening for coeliac disease (CD) should be performed in patients with chronic unexplained hypertransaminasaemia. <h3>AIMS</h3> To evaluate the specificity for CD diagnosis of serum IgA antitissue transglutaminase (tTG) determination in consecutive patients with chronic hypertransaminasaemia using the most widely utilised ELISA based on tTG from guinea pig as the antigen. <h3>PATIENTS AND METHODS</h3> We studied 98 patients with chronic hypertransaminasaemia, evaluated for the first time in a hepatology clinic. Serum anti-tTG and antiendomysial (EmA) assays were performed. Patients positive for EmA and/or anti-tTG were proposed for intestinal biopsy. Finally, all sera were reassayed for anti-tTG using an ELISA based on human recombinant tTG as the antigen. <h3>RESULTS</h3> A total of 94/98 hypertransaminasaemic patients were positive for hepatitis virus markers, with 82/98 (83%) positive for anti-hepatitis C virus. Liver histology showed that most patients had mild or moderate chronic hepatitis while severe fibrosis or overt liver cirrhosis was found in 20/98. CD screening showed that 15/98 (16%) hypertransaminasaemic subjects had anti-tTG values in the same range as CD patients; however, IgA EmA were positive in only 2/98 (2%). Distal duodenal biopsy, performed in nine patients, showed subtotal villous atrophy in the two EmA+/anti-tTG+ patients but was normal in 7/7 EmA−/anti-tTG+ subjects. The presence of anti-tTG+ values in EmA− patients was unrelated to particular gastrointestinal symptoms, other associated diseases, severity of liver histology, or distribution of viral hepatitis markers. There was a significantly higher frequency of positive serum autoantibodies (antinuclear, antimitochondrial, antismooth muscle, and anti-liver-kidney microsomal antibodies) in anti-tTG+/EmA− patients than in the other subjects (9/13<i>v </i>10/83; p&lt;0.003). Also, a correlation was found between serum gamma globulin and anti-tTG values (p&lt;0.01). When sera were tested with the ELISA based on human tTG as the antigen, no false positive results were observed: only the two EmA+ patients with atrophy of the intestinal mucosa were positive for anti-tTG while all others were negative, including those false positive in the ELISA based on guinea pig tTG as the antigen. <h3>CONCLUSIONS</h3> In patients with elevated transaminases and chronic liver disease there was a high frequency of false positive anti-tTG results using the ELISA based on tTG from guinea pig as the antigen. Indeed, the presence of anti-tTG did not correlate with the presence of EmA or CD. These false positives depend on the presence of hepatic proteins in the commercial tTG obtained from guinea pig liver and disappear when human tTG is used as the antigen in the ELISA system. We suggest that the commonly used tTG ELISA based on guinea pig antigen should not be used as a screening tool for CD in patients with chronic liver disease.
Immunobiology of Dendritic Cells
Authors: Jacques Banchereau, Francine Briere, Christophe Caux, Jean Davoust, Serge Lebecque, Yong-Jun Liu, Bali Pulendran, Karolina Palucka
Journal: Annual Review of Immunology (2000)

Dendritic cells (DCs) are antigen-presenting cells with a unique ability to induce primary immune responses. DCs capture and transfer information from the outside world to the cells of the adaptive immune system. DCs are not only critical for the induction of primary immune responses, but may also be important for the induction of immunological tolerance, as well as for the regulation of the type of T cell–mediated immune response. Although our understanding of DC biology is still in its infancy, we are now beginning to use DC-based immunotherapy protocols to elicit immunity against cancer and infectious diseases.
A Diabetes Report Card for the United States: Quality of Care in the 1990s
Authors: Jinan B. Saaddine, Michael M. Engelgau, Gloria L. Beckles, Edward W. Gregg, Theodore J. Thompson, K.M. Venkat Narayan
Journal: Annals of Internal Medicine (2002)

Improving diabetes care in the United States is a topic of concern.To document the quality of diabetes care during 1988-1995.National population-based cross-sectional surveys.Third U.S. National Health and Nutrition Examination Survey (NHANES III) (1988-1994) and the Behavioral Risk Factors Surveillance System (BRFSS) (1995).Participants in NHANES III (n = 1026) or BRFSS (n = 3059) who were 18 to 75 years of age and reported a physician diagnosis of diabetes. Women with gestational diabetes were excluded.Glycemic control, blood pressure, low-density lipoprotein (LDL) cholesterol level, biannual cholesterol monitoring, and annual foot and dilated eye examination, as defined by the Diabetes Quality Improvement Project.18.0% of participants (95% CI, 15.7% to 22.3%) had poor glycemic control (hemoglobin A(1c) level > 9.5%), and 65.7% (CI, 62.0% to 69.4%) had blood pressure less than 140/90 mm Hg. Cholesterol was monitored biannually in 85.3% (CI, 83.1% to 88.6%) of participants, but only 42.0% (CI, 34.9% to 49.1%) had LDL cholesterol levels less than 3.4 mmol/L (<130 mg/dL). During the previous year, 63.3% (CI, 59.6% to 67.0%) had a dilated eye examination and 54.8% (CI, 51.3% to 58.3%) had a foot examination. When researchers controlled for age, sex, ethnicity, education, health insurance, insulin use, and duration of diabetes, insured persons were more likely than uninsured persons to have a dilated eye examination (66.5% [CI, 62.6% to 70.4%]) vs. 43.2% [CI, 29.5% to 56.9%]) and were less likely to have a hemoglobin A(1c)level greater than or equal to 9.5%. Persons taking insulin were more likely than those who were not to have annual dilated eye examination (72.2% [CI, 66.3% to 78.1%] vs. 57.6% [CI, 53.7% to 61.5%]) and foot examination (67.3% [CI, 61.4% to 73.2%] vs. 47.1% [CI, 43.2% to 51.0%]) but were also more likely to have poor glycemic control (24.2% [CI, 18.3% to 30.1%] vs. 15.5% [CI, 11.6% to 19.4%]).According to U.S. data collected during 1988-1995, a gap exists between recommended diabetes care and the care patients actually receive. These data offer a benchmark for monitoring changes in diabetes care.
FL-41 Tint Improves Blink Frequency, Light Sensitivity, and Functional Limitations in Patients with Benign Essential Blepharospasm
Authors: Marcus K. Blackburn, Randy D. Lamb, Kathleen B. Digre, A. Gordon Smith, Judith E.A. Warner, Robert W. McClane, Sanjeev D. Nandedkar, Wendy J. Langeberg, Richard Holubkov, Bradley J. Katz
Journal: Ophthalmology (2009)
Biased Agonist Pharmacochaperones of the AVP V2 Receptor May Treat Congenital Nephrogenic Diabetes Insipidus
Authors: Frédéric Jean-Alphonse, Sanja Perkovska, Marie-Céline Frantz, Thierry Durroux, Catherine Méjean, Denis Morin, Stéphanie Loison, Dominique Bonnet, Marcel Hibert, Bernard Mouillac, Christiane Mendre
Journal: Journal of the American Society of Nephrology (2009)

X-linked congenital nephrogenic diabetes insipidus (cNDI) results from inactivating mutations of the human arginine vasopressin (AVP) V2 receptor (hV(2)R). Most of these mutations lead to intracellular retention of the hV(2)R, preventing its interaction with AVP and thereby limiting water reabsorption and concentration of urine. Because the majority of cNDI-hV(2)Rs exhibit protein misfolding, molecular chaperones hold promise as therapeutic agents; therefore, we sought to identify pharmacochaperones for hV(2)R that also acted as agonists. Here, we describe high-affinity nonpeptide compounds that promoted maturation and membrane rescue of L44P, A294P, and R337X cNDI mutants and restored a functional AVP-dependent cAMP signal. Contrary to pharmacochaperone antagonists, these compounds directly activated a cAMP signal upon binding to several cNDI mutants. In addition, these molecules displayed original functionally selective properties (biased agonism) toward the hV(2)R, being unable to recruit arrestin, trigger receptor internalization, or stimulate mitogen-activated protein kinases. These characteristics make these hV(2)R agonist pharmacochaperones promising therapeutic candidates for cNDI.
Regulation of Cancer Progression by β-Endorphin Neuron
Authors: Dipak K. Sarkar, Sengottuvelan Murugan, Changqing Zhang, Nadka Boyadjieva
Journal: Cancer Research (2012)

It is becoming increasingly clear that stressful life events can affect cancer growth and metastasis by modulating nervous, endocrine, and immune systems. The purpose of this review is to briefly describe the process by which stress may potentiate carcinogenesis and how reducing body stress may prevent cancer growth and progression. The opioid peptide β-endorphin plays a critical role in bringing the stress axis to a state of homeostasis. We have recently shown that enhancement of endogenous levels of β-endorphin in the hypothalamus via β-endorphin neuron transplantation suppresses stress response, promotes immune function, and reduces the incidence of cancer in rat models of prostate and breast cancers. The cancer-preventive effect of β-endorphin is mediated through the suppression of sympathetic neuronal function, which results in increased peripheral natural killer cell and macrophage activities, elevated levels of anti-inflammatory cytokines, and reduced levels of inflammatory cytokines. β-endorphin inhibition of tumor progression also involves alteration in the tumor microenvironment, possibly because of suppression of catecholamine and inflammatory cytokine production, which are known to alter DNA repair, cell-matrix attachments, angiogenic process, and epithelial-mesenchymal transition. Thus, β-endorphin cell therapy may offer some therapeutic value in cancer prevention.
What working memory is for
Authors: Robert H. Logie
Journal: Behavioral and Brain Sciences (1997)

Glenberg focuses on conceptualizations that change from moment to moment, yet he dismisses the concept of working memory (sect. 4.3), which offers an account of temporary storage and on-line cognition. This commentary questions whether Glenberg's account adequately caters for observations of consistent data patterns in temporary storage of verbal and visuospatial information in healthy adults and in brain-damaged patients with deficits in temporary retention.
Ototoxicity in Patients With Dose-Intensive Therapy for Cisplatin-Resistant Germ Cell Tumors
Authors: Adrian Dubs, Emanuel Jacky, Rolf Stahel, Christian Taverna, Hanspeter Honegger
Journal: Journal of Clinical Oncology (2004)

durable complete remission (rate, 57%) after dose-intense sequential, accelerated chemotherapy with paclitaxel ifosfamide and three cycles of high-dose carboplatin etoposide (mean target carboplatin area under the curve [AUC] of 24 [mg/mL] minute per cycle) followed by peripheral blood-derived stem-cell support in patients with cisplatin-resistant germ cell tumors. Hearing impairment or deafness were not reported as adverse effects. Carboplatin-induced ototoxicity in different high-dose combination regimens has been described by other investigators [2,3]. Between October 2000 and August 2002, we treated nine patients with resistant or recurrent germ cell tumors according to the regimen described by Motzer et al, with three cycles of high-dose carboplatin etoposide (carboplatin AUC of 24 [mg/mL] minute). All patients were pretreated with as many as four cycles of cisplatin-containing chemotherapy. At the beginning of the dose-intense therapy, none of the patients had a clinically obvious hearing impairment. During treatment, all of them started to suffer from hearing disorders and finally developed a clinically manifested hearing impairment. Audiometry revealed bilateral high-frequency sensorineural hearing loss (above 2,000 Hz), with tinnitus in six patients; three of them needed a hearing aid. Hearing impairment was apparent in the other three patients as well, though audiometry was not done. Our experience confirms the favorable results in this group of patients with poor prognosis (five of nine patients are in durable complete remission; complete remission rate, 56%), whereas the ototoxicity observed with this regimen is a considerable adverse effect. Ototoxicity seems to be strongly related to the cumulative carboplatin AUC [3]. High-dose carboplatin is thought to be important to obtain favorable results in patients with relapsed or resistant germ cell tumors. Clinicians should be aware of the possible severe ototoxicity with this regimen, and patients undergoing multiple cycles of carboplatin-containing high-dose chemotherapy should be informed about this relevant toxicity.
Forced Mitotic Entry of S-Phase Cells as a Therapeutic Strategy Induced by Inhibition of WEE1
Authors: Marieke Aarts, Rachel Sharpe, Isaac Garcia-Murillas, Heidrun Gevensleben, Melissa S. Hurd, Stuart D. Shumway, Carlo Toniatti, Alan Ashworth, Nicholas C. Turner
Journal: Cancer Discovery (2012)

Inhibition of the protein kinase WEE1 synergizes with chemotherapy in preclinical models and WEE1 inhibitors are being explored as potential cancer therapies. Here, we investigate the mechanism that underlies this synergy. We show that WEE1 inhibition forces S-phase-arrested cells directly into mitosis without completing DNA synthesis, resulting in highly abnormal mitoses characterized by dispersed chromosomes and disorganized bipolar spindles, ultimately resulting in mitotic exit with gross micronuclei formation and apoptosis. This mechanism of cell death is shared by CHK1 inhibitors, and combined WEE1 and CHK1 inhibition forces mitotic entry from S-phase in the absence of chemotherapy. We show that p53/p21 inactivation combined with high expression of mitotic cyclins and EZH2 predispose to mitotic entry during S-phase with cells reliant on WEE1 to prevent premature cyclin-dependent kinase (CDK)1 activation. These features are characteristic of aggressive breast, and other, cancers for which WEE1 inhibitor combinations represent a promising targeted therapy.