tbuckley/cabot-search huggingface dataset:
Dobutamine echocardiography for determining the extent of myocardial salvage after reperfusion. An experimental evaluation.
Authors: J Sklenar, S Ismail, F S Villanueva, N C Goodman, W P Glasheen, S Kaul
Journal: Circulation (1994)

Although dobutamine echocardiography is being increasingly used to determine the presence of viable myocardium in patients who have undergone successful reperfusion therapy, the physiological basis for such a use has not been clearly defined. Because postischemic myocardium has contractile reserve, we hypothesized that the absolute degree of wall thickening induced by dobutamine during reflow would be directly related to the amount of myocardium that has escaped necrosis.Three groups of 12 dogs each were studied at baseline and during 2 to 6 hours of coronary artery occlusion and 15 minutes of reperfusion. In group 1 dogs, which did not receive dobutamine during any of these stages, percent wall thickening at these stages was 32 +/- 6%, -2 +/- 6%, and 5 +/- 6%, respectively, and there was no relation between infarct size and percent wall thickening during reflow (r = .20, P = .51). In group 2 dogs, which received 15 micrograms/kg per minute of dobutamine at all stages, wall thickening at these stages was 40 +/- 8%, 0 +/- 8%, and 19 +/- 10%, respectively, and a good inverse correlation was noted between infarct size and percent wall thickening during reflow (r = -.81, P = .001). In group 3 dogs, in which wall thickening during reflow was measured both before and during infusion of 15 micrograms/kg per minute of dobutamine, it was 5 +/- 8% and 18 +/- 14%, respectively, at these stages. Although the correlation between infarct size and percent wall thickening was poor in the absence of dobutamine (r = .36, P = .26), an excellent inverse correlation was noted between the two in the presence of dobutamine (r = -.93, P < .001). A fair inverse correlation was also noted between infarct size and the absolute change in wall thickening induced by dobutamine (r = -.72, P < .01). Maximal wall thickening was noted at a dobutamine dose of 15 micrograms/kg per minute, and lower doses did not elicit thickening in the presence of larger infarcts despite the presence of viable myocardium.When myocardial necrosis coexists with post-ischemic myocardial dysfunction and no residual coronary stenosis, the absolute degree of wall thickening during dobutamine can be used to determine the extent of myocardium that has escaped necrosis. The dose of dobutamine needed to elicit maximal thickening of the postischemic myocardium is related to the amount of myocardial necrosis.
Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation.
Authors: F M Muggia, J D Hainsworth, S Jeffers, P Miller, S Groshen, M Tan, L Roman, B Uziely, L Muderspach, A Garcia, A Burnett, F A Greco, C P Morrow, L J Paradiso, L J Liang
Journal: Journal of Clinical Oncology (1997)

A phase II study of liposomal doxorubicin was conducted in patients with ovarian cancer who failed to respond to platinum- and paclitaxel-based regimens. Liposomal doxorubicin was selected as a result of its superior activity against ovarian cancer xenografts relative to free doxorubicin and activity in refractory ovarian cancer patients that was noted during the phase I study.Thirty-five consecutive patients were accrued in two institutions (22 in one and 13 in the other). All had progressive disease after either cisplatin or carboplatin and paclitaxel, or at least one platinum-based and one paclitaxel-based regimen. Patients received intravenous (I.V.) liposomal doxorubicin 50 mg/m2 every 3 weeks with a dose reduction to 40 mg/m2 in the event of grade 3 or 4 toxicities, or a lengthening of the interval to 4 weeks (and occasionally to 5 weeks) with persistence of grade 1 or 2 toxicities beyond 3 weeks.Nine clinical responses (one complete response [CR], eight partial responses [PRs]) were observed in 35 patients (25.7%), with seven of these having been confirmed by two consecutive computed tomographic (CT) measurements. The median progression-free survival was 5.7 months with an overall survival of 1.5 to 24+ months (median, 11 months). Although 13 patients experienced grade 3 or 4 nonhematologic skin and mucosal toxicities (either hand-foot syndrome or stomatitis), with dose modifications, the treatment was very well tolerated. Nausea that was clearly attributable to the drug, hair loss, extravasation necrosis, or decreases in ejection fraction did not occur.Liposomal doxorubicin has substantial activity against ovarian cancer refractory to platinum and paclitaxel. The responses achieved with liposomal doxorubicin were durable and maintained with minimal toxicity. This liposomal formulation should be evaluated further in combination with other drugs in less refractory patients.
Adjuvant Immunotherapy of Resected, Intermediate-Thickness, Node-Negative Melanoma With an Allogeneic Tumor Vaccine: Overall Results of a Randomized Trial of the Southwest Oncology Group
Authors: Vernon K. Sondak, P.-Y. Liu, Ralph J. Tuthill, Raymond A. Kempf, Joseph M. Unger, Jeffrey A. Sosman, John A. Thompson, Geoffrey R. Weiss, Bruce G. Redman, James G. Jakowatz, R. Dirk Noyes, Lawrence E. Flaherty
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Patients with clinically negative nodes constitute over 85% of new melanoma cases. There is no adjuvant therapy for intermediate-thickness, node-negative melanoma patients. PATIENTS AND METHODS: The Southwest Oncology Group conducted a randomized phase III trial of an allogeneic melanoma vaccine for 2 years versus observation in patients with intermediate-thickness (1.5 to 4.0 mm or Clark’s level IV if thickness unknown), clinically or pathologically node-negative melanoma (T3N0M0). RESULTS: Six hundred eighty-nine patients were accrued over 4.5 years; 89 patients (13%) were ineligible. Surgical node staging was performed in 24%, the remainder were clinical N0. Thirteen eligible patients refused assigned treatment: seven on the observation arm and six on the vaccine arm. Most vaccine patients experienced mild to moderate local toxicity, but 26 (9%) experienced grade 3 toxicity. After a median follow-up of 5.6 years, there were 107 events (tumor recurrences or deaths) among the 300 eligible patients randomized to vaccine compared with 114 among the 300 eligible patients randomized to observation (hazard ratio, 0.92; Cox-adjusted P 2 = 0.51). There was no difference in vaccine efficacy among patients with tumors ≤ 3 mm or &gt; 3 mm. CONCLUSION: This represents one of the largest randomized, controlled trials of adjuvant vaccine therapy in human cancer reported to date. Compliance with randomization was excellent, with only 2% refusing assigned therapy. There is no evidence of improved disease-free survival among patients randomized to receive vaccine, although the power to detect a small but clinically significant difference was low. Future investigations of adjuvant vaccine approaches for patients with intermediate-thickness melanoma should involve larger numbers of patients and ideally should include sentinel node biopsy staging.
OBSERVATIONS ON THE ILEO-CAECAL VALVE IN MAN
Authors: A. R. Short
Journal: BMJ (1919)

TitE ILEO-CAKCAL VALVE IN MAN.from a new infection with such remarkable rapidity after a few irrigations with potassiam permanganate, the solution freely entering the lacunae and flushing them out.It is advisable to stock at least a couple of these tubes,
Decreased susceptibility to renovascular hypertension in mice lacking the prostaglandin I2 receptor IP
Authors: Takayuki Fujino, Naoki Nakagawa, Koh-ichi Yuhki, Akiyoshi Hara, Takehiro Yamada, Koji Takayama, Shuhko Kuriyama, Yayoi Hosoki, Osamu Takahata, Takanobu Taniguchi, Jun Fukuzawa, Naoyuki Hasebe, Kenjiro Kikuchi, Shuh Narumiya, Fumitaka Ushikubi
Journal: Journal of Clinical Investigation (2004)

Persistent reduction of renal perfusion pressure induces renovascular hypertension by activating the renin-angiotensin-aldosterone system; however, the sensing mechanism remains elusive. Here we investigated the role of PGI2 in renovascular hypertension in vivo, employing mice lacking the PGI2 receptor (IP-/- mice). In WT mice with a two-kidney, one-clip model of renovascular hypertension, the BP was significantly elevated. The increase in BP in IP-/- mice, however, was significantly lower than that in WT mice. Similarly, the increases in plasma renin activity, renal renin mRNA, and plasma aldosterone in response to renal artery stenosis were all significantly lower in IP-/- mice than in WT mice. All these parameters were measured in mice lacking the four PGE2 receptor subtypes individually, and we found that these mice had similar responses to WT mice. PGI2 is produced by COX-2 and a selective inhibitor of this enzyme, SC-58125, also significantly reduced the increases in plasma renin activity and renin mRNA expression in WT mice with renal artery stenosis, but these effects were absent in IP-/- mice. When the renin-angiotensin-aldosterone system was activated by salt depletion, SC-58125 blunted the response in WT mice but not in IP-/- mice. These results indicate that PGI2 derived from COX-2 plays a critical role in regulating the release of renin and consequently renovascular hypertension in vivo.
Effect of Structured Physical Activity on Prevention of Major Mobility Disability in Older Adults
Authors: Marco Pahor, Jack M. Guralnik, Walter T. Ambrosius, Steven Blair, Denise E. Bonds, Timothy S. Church, Mark A. Espeland, Roger A. Fielding, Thomas M. Gill, Erik J. Groessl, Abby C. King, Stephen B. Kritchevsky, Todd M. Manini, Mary M. McDermott, Michael E. Miller, Anne B. Newman, W. Jack Rejeski, Kaycee M. Sink, Jeff D. Williamson
Journal: JAMA (2014)

In older adults reduced mobility is common and is an independent risk factor for morbidity, hospitalization, disability, and mortality. Limited evidence suggests that physical activity may help prevent mobility disability; however, there are no definitive clinical trials examining whether physical activity prevents or delays mobility disability.To test the hypothesis that a long-term structured physical activity program is more effective than a health education program (also referred to as a successful aging program) in reducing the risk of major mobility disability.The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter, randomized trial that enrolled participants between February 2010 and December 2011, who participated for an average of 2.6 years. Follow-up ended in December 2013. Outcome assessors were blinded to the intervention assignment. Participants were recruited from urban, suburban, and rural communities at 8 centers throughout the United States. We randomized a volunteer sample of 1635 sedentary men and women aged 70 to 89 years who had physical limitations, defined as a score on the Short Physical Performance Battery of 9 or below, but were able to walk 400 m.Participants were randomized to a structured, moderate-intensity physical activity program (n = 818) conducted in a center (twice/wk) and at home (3-4 times/wk) that included aerobic, resistance, and flexibility training activities or to a health education program (n = 817) consisting of workshops on topics relevant to older adults and upper extremity stretching exercises.The primary outcome was major mobility disability objectively defined by loss of ability to walk 400 m.Incident major mobility disability occurred in 30.1% (246 participants) of the physical activity group and 35.5% (290 participants) of the health education group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98], P = .03).Persistent mobility disability was experienced by 120 participants (14.7%) in the physical activity group and 162 participants (19.8%) in the health education group (HR, 0.72 [95% CI, 0.57-0.91]; P = .006). Serious adverse events were reported by 404 participants (49.4%) in the physical activity group and 373 participants (45.7%) in the health education group (risk ratio, 1.08 [95% CI, 0.98-1.20]).A structured, moderate-intensity physical activity program compared with a health education program reduced major mobility disability over 2.6 years among older adults at risk for disability. These findings suggest mobility benefit from such a program in vulnerable older adults.clinicaltrials.gov Identifier: NCT01072500.
Thyroid hormone transport in the serum of patients with thyrotoxic graves' disease before and after treatment
Authors: Lewis E. Braverman, Angela E. Foster, Sidney H. Ingbar
Journal: Journal of Clinical Investigation (1968)

Multiple indices of thyroid hormone binding have been studied in sera obtained from patients with thyrotoxic Graves' disease, before and after treatment, and in sera from a group of carefully matched normal controls. Specimens from patients with thyrotoxicosis displayed a decrease in the thyroxine (T(4))-binding capacities of T(4)-binding globulin (TBG) and T(4)-binding prealbumin (TBPA), an increase in serum protein-bound iodine (PBI), and an increase in both the proportion and absolute concentration of free T(4). In addition, a smaller than normal proportion of (131)I-labeled T(3) was associated with TBG during filter paper electrophoresis. After treatment of thyroxicosis, the only residual abnormality detected was a very slight persistent decrease in the T(4)-binding capacity of TBPA, which did not appear to influence the overall thyroid hormone-plasma protein interaction significantly, regardless of whether this was assessed under basal conditions or after enrichment of specimens with stable T(4). It is concluded that the persistent abnormalities in the peripheral metabolism of T(4), previously reported to occur in some patients with treated Graves' disease, probably do not stem from residual abnormalities in the transport of T(4) in the plasma but must arise from abnormalities in T(4) accumulation or metabolism within the tissues themselves.
Antiadrenergic Antihypertensive Drugs: Their Effect on Renal Function
Authors: K N Bernstein, D T O'Connor
Journal: The Annual Review of Pharmacology and Toxicology (1984)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
Apoptotic pathways in pancreatic ductal adenocarcinoma
Authors: Rainer Hamacher, Roland M Schmid, Dieter Saur, Günter Schneider
Journal: Molecular Cancer (2008)

Pancreatic ductal adenocarcinoma (PDAC) is one of the most common causes of cancer related death. Despite the advances in understanding of the molecular pathogenesis, pancreatic cancer remains a major unsolved health problem. Overall, the 5-year survival rate is less than 5% demonstrating the insufficiency of current therapies. Most cytotoxic therapies induce apoptosis and PDAC cells have evolved a plethora of molecular mechanisms to assure survival. We will present anti-apoptotic strategies working at the level of the death receptors, the mitochondria or involving the caspase inhibitors of the IAP family. Furthermore, the survival function of the phosphotidylinositol-3' kinase (PI3K)/AKT- and NF-kappaB-pathways are illustrated. A detailed molecular knowledge of the anti-apoptotic mechanisms of PDAC cells will help to improve therapies for this dismal disease and therapeutic strategies targeting the programmed cell death machinery are in early preclinical and clinical development.
Asp905Tyr Polymorphism of the Gene for the Skeletal Muscle-Specific Glycogen-Targeting Subunit of Protein Phosphatase 1 in NIDDM
Authors: Gong-Qing Shen, Hiroshi Ikegami, Yoshihiko Kawaguchi, Tomomi Fujisawa, Yoichi Hamada, Hironori Ueda, Maki Shintani, Koji Nojima, Yumiko Kawabata, Kazunori Yamada, Naru Babaya, Toshio Ogihara
Journal: Diabetes Care (1998)

OBJECTIVE To clarify the contribution of the Asp905Tyr polymorphism of the musclespecific glycogen-targeting subunit of protein phosphatase 1 (PP1G) to insulin resistance and related diseases. RESEARCH DESIGN AND METHODS We investigated the Asp905Tyr polymorphism of the PPP1R3 gene, which encodes the muscle-specific glycogen-targeting subunit of PP1G, in 259 Japanese patients with NIDDM and 194 healthy control subjects. RESULTS No significant difference was found in the genotype distribution between NIDDM patients (n = 259; Asp/Asp = 0.10, Asp/Tyr = 0.44, Tyr/Tyr = 0.46) and healthy control subjects (n = 194; Asp/Asp = 0.13, Asp/Tyr = 0.37, Tyr/Tyr = 0.50) or between patient groups subdivided by the mode of treatment: NIDDM patients with insulin therapy (Asp/Asp = 0.14, Asp/Tyr = 0.46, Tyr/Tyr = 0.40) and those without insulin therapy (Asp/Asp = 0.07, Asp/Tyr = 0.43, Tyr/Tyr = 0.50). However, NIDDM patients with the Tyr allele, which was previously reported to be associated with insulin resistance, tended to have lower BMIs than those without this allele (Asp/Asp: 24.5 ±1.1 kg/m2, Asp/Tyr: 22.6 ± 0.4 kg/m2, Tyr/Tyr: 22.8 + 0.3 kg/m2, P = 0.06 by analysis of variance). CONCLUSIONS These data suggest that the Asp905Tyr polymorphism of the PPP1R3 gene is not associated with NIDDM or high BMI, both of which are known to be insulin-resistant states, in the Japanese population.
Direct Volumetric Blood Flow Measurement in Coronary Arteries by Thermodilution
Authors: Wilbert Aarnoudse, Marcel van’t Veer, Nico H.J. Pijls, Joost ter Woorst, Steven Vercauteren, Pim Tonino, Maartje Geven, Marcel Rutten, Eduard van Hagen, Bernard de Bruyne, Frans van de Vosse
Journal: Journal of the American College of Cardiology (2007)
Integrins as Target: First Phase III Trial Launches, but Questions Remain
Authors: Andrea Carter
Journal: JNCI Journal of the National Cancer Institute (2010)

C ellular glue, signaling molecule, cancer accessory — scientists have described various functions for the integrin cellular receptors since the 1970s. And now they may be adding another role to the list: For the first time, an integrin as a target for cancer therapy has made it to a phase III clinical trial. Merck KGaA, based in Germany, is sponsoring the trial to test cilengitide, an RGD (arginine – glycine – aspartic acid) peptide targeting an integrin involved in angiogenesis, for the brain cancer glioblastoma. The study, led by Roger Stupp, M.D., at the University of Lausanne Hospital in Lausanne, Switzerland, is currently recruiting more than 500 patients from Asia, Europe, and North America. “Cilengitide is up front, and if it continues to look good, it will be the fi rst drug of this kind to be approved,” said David Cheresh, Ph.D., at the University of California at San Diego in La Jolla, who worked on the early preclinical studies with the drug. But whether more integrin-targeted drugs will appear remains uncertain. One unanswered question about anti-integrin drugs in general concerns their effects on normal cells. What makes integrins a potentially effective cancer therapy target, their key role in cell survival, also makes them a tricky mark because many of the receptors are active in both normal and cancer cells. Also, some preclinical studies suggest that anti-integrin compounds can promote cancerous activity. “The limitation of these drugs could be toxicity,” said Filippo Giancotti, M.D., Ph.D., at the Sloan – Kettering Institute in New York, who studies integrins in normal development and cancer.
Health effects of passive smoking. 3. Parental smoking and prevalence of respiratory symptoms and asthma in school age children
Authors: D. G. Cook, D. P. Strachan
Journal: Thorax (1997)

BACKGROUND: A systematic quantitative review of the evidence relating parental smoking to the prevalence of asthma and respiratory symptoms was conducted amongst school age children. METHODS: Sixty relevant studies were identified after consideration of 1593 articles selected by electronic search of the Embase and Medline databases using keywords relevant to passive smoking in children. The search was completed in April 1997 and identified 25 studies of asthma, 41 of wheeze, 34 of chronic cough, seven of chronic phlegm and six of breathlessness which were included in a quantitative overview. RESULTS: The pooled odds ratios for either parent smoking were 1.21 (95% CI 1.10 to 1.34) for asthma, 1.24 (95% CI 1.17 to 1.31) for wheeze, 1.40 (95% CI 1.27 to 1.53) for cough, 1.35 (95% CI 1.13 to 1.62) for phlegm, and 1.31 (95% CI 1.08 to 1.59) for breathlessness. Adjustment for confounding had little effect. Evidence of heterogeneity between studies appeared largely explicable by publication bias with a superfluity of small studies with large odds ratios. However, excluding these had little effect on the pooled odds ratios. The prevalence of all symptoms increased with the number of parents who smoked. While maternal smoking had a greater effect than paternal smoking, the effect of father only was clearly significant. CONCLUSIONS: The relationship between parental smoking and respiratory symptoms seems very likely to be causal given statistical significance, robustness to adjustment for confounding factors, consistency of the findings in different countries, and evidence of dose response. The raised risk in households where the father, but not the mother, smoked argues for a postnatal effect.
Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients
Authors: John M. Timmerman, Debra K. Czerwinski, Thomas A. Davis, Frank J. Hsu, Claudia Benike, Zheng Mei Hao, Behnaz Taidi, Ranjani Rajapaksa, Clemens B. Caspar, Craig Y. Okada, Adrienne van Beckhoven, Tina Marie Liles, Edgar G. Engleman, Ronald Levy
Journal: Blood (2002)
MiR-124 governs glioma growth and angiogenesis and enhances chemosensitivity by targeting R-Ras and N-Ras
Authors: Zhumei Shi, Qiudan Chen, Chongyong Li, Lin Wang, Xu Qian, Chengfei Jiang, Xue Liu, Xiefeng Wang, Hai Li, Chunsheng Kang, Tao Jiang, Ling-Zhi Liu, Yongping You, Ning Liu, Bing-Hua Jiang
Journal: Neuro-Oncology (2014)

Glioma is one of the most aggressive and lethal human brain tumors. Accumulating evidence shows that microRNAs play important roles in cancers, including glioma. Previous studies reported that miR-124 levels were downregulated in glioma specimens. Here, we further investigate the potential role of miR-124 in glioma. The expression levels of miR-124 were detected in glioma specimens by quantitative reverse transcriptase PCR. The direct targets of miR-124 were identified by bioinformatics analysis and were further validated by immunoblotting and luciferase reporter assay. The effects of miR-124 on glioma cell proliferation and chemosensitivity to temozolomide were analyzed by Cell-Counting Kit 8 assay. Apoptosis was evaluated by fluorescence activated cell sorting analysis. A xenograft model was used to study the effect of miR-124 on tumor growth and angiogenesis. Expression levels of miR-124 were greatly downregulated in glioma specimens. related Ras viral oncogene homolog (R-Ras) and neuroblastoma Ras viral oncogene homolog (N-Ras) were identified as direct targets of miR-124. MiR-124 inhibited glioma cell growth, invasion, angiogenesis, and tumor growth and increased chemosensitivity to temozolomide treatment by negatively regulating the Ras family and its downstream signaling pathways: phosphatidylinositol-3 kinase/Akt and Raf/extracellular signal-regulated kinase 1/2. Furthermore, overexpression of R-Ras rescued the inhibitory effects of miR-124. Meanwhile, overexpression of R-Ras and N-Ras restored miR-124–inhibited vascular endothelial growth factor (VEGF) transcription activation. In clinical glioma specimens, protein levels of R-Ras and N-Ras were upregulated and inversely correlated with miR-124 expression levels. Taken together, these results revealed that miR-124 levels in tumor tissues are associated with glioma occurrence, angiogenesis, and chemoresistance and that miR-124 may be used as a new diagnostic marker and therapeutic target for glioma in the future.