tbuckley/cabot-search huggingface dataset:
Specific accumulation of technetium-99m radiolabelled, negative liposomes in the inflamed paws of rats with adjuvant induced arthritis: effect of liposome size.
Authors: W G Love, N Amos, I W Kellaway, B D Williams
Journal: Annals of the Rheumatic Diseases (1989)

Technetium-99m labelled, negatively charged liposomes accumulate in the inflamed tissue of rats with adjuvant induced arthritis. Up to 10 times more liposome accumulation was seen in inflamed paws than in paws of control rats, and this represented 5.3% of the injected liposome dose. The accumulation of liposomes in inflamed tissue was directly related to the liposome size, the maximal accumulation occurring with liposomes less than 100 nm in diameter.
Nucleic Acid Synthesis in Enlarged Hearts of Rats with Nutritional Anemia
Authors: BORIVOJ KORECKY, IAN W. FRENCH, R. A. Layberry, A. M. McKerral
Journal: Circulation Research (1967)

Cardiac enlargement was produced in three groups of male rats by maintaining them on a diet low in iron. Hearts from anemic rats increased approximately 100% in weight compared to hearts from normal rats. When compared to control cardiac tissue, no consistent significant changes in the concentration of DNA, RNA, or protein occurred in any of the groups. The total amount of all three constituents increased significantly in the enlarged hearts; this increase was proportional to the degree of cardiac enlargement. The data indicate that nuclear and cytoplasmic material increased equally in cardiac enlargement due to nutritional anemia. This and other observations in the literature suggest hyperplasia as the most likely explanation.
Injection of mice with antibody to interferon enhances the growth of transplantable murine tumors.
Authors: I Gresser, F Belardelli, C Maury, M T Maunoury, M G Tovey
Journal: The Journal of Experimental Medicine (1983)

Injection of DBA/2, C57Bl/6, or BALB/c mice with antibody to mouse interferon alpha/beta enhanced the i.p. transplantability of six different murine tumors, as manifested by an increase in the percentage of tumor-bearing mice and a decrease in survival time. The effect was observed in mice injected with antibody to interferon raised in three sheep, a goat, and a rabbit, but not with sheep antibody to "impurities" present in the mouse interferon preparations or with normal sheep or goat globulins. The enhancement in transplantability was most marked when tumor cells had been previously passaged in vitro and were of low tumorigenicity. Analysis of some of the experimental conditions using interferon-sensitive and interferon-resistant lines of Friend erythroleukemia cells (FLC) showed that the enhancing effect was observed over a wide range of tumor cell inocula, was directly related to the amount of antibody to interferon injected and was most pronounced when antibody was administered at the time of tumor cell injection. Enhancement was also observed when FLC were injected subcutaneously (s.c.). Antibody did not act directly on the tumor cells in vitro. Although we were unable to demonstrate any biologically active interferon in mice before or after tumor cell inoculation, the results suggest that endogenous interferon is present and plays a role in inhibiting the transplantability of some murine tumors in immunocompetent mice.
Involvement of the Brain (Pro)renin Receptor in Cardiovascular Homeostasis
Authors: Zhiying Shan, Peng Shi, Adolfo E. Cuadra, Ying Dong, Gwyneth J. Lamont, Qiuhong Li, Dale M. Seth, L. Gabriel Navar, Michael J. Katovich, Colin Sumners, Mohan K. Raizada
Journal: Circulation Research (2010)

Rationale: Despite overwhelming evidence of the importance of brain renin–angiotensin system (RAS), the very existence of intrinsic brain RAS remains controversial. Objective: To investigate the hypothesis that the brain (pro)renin receptor (PRR) is physiologically important in the brain RAS regulation and cardiovascular functions. Methods and Results: PRR is broadly distributed within neurons of cardiovascular-relevant brain regions. The physiological functions of PRR were studied in the supraoptic nucleus (SON) because this brain region showed greater levels of PRR mRNA in the spontaneously hypertensive rats (SHR) compared with normotensive Wistar–Kyoto (WKY) rats. Adeno-associated virus (AAV)-mediated overexpression of human PRR in the SON of normal rats resulted in increases in plasma and urine vasopressin, and decreases in H 2 O intake and urine output without any effects on mean arterial pressure and heart rate. Knockdown of endogenous PRR by AAV-short hairpin RNA in the SON of SHRs attenuated age-dependent increases in mean arterial pressure and caused a decrease in heart rate and plasma vasopressin. Incubation of neuronal cells in culture with human prorenin and angiotensinogen resulted in increased generation of angiotensin I and II. Furthermore, renin treatment increased phosphorylation of extracellular signal-regulated kinase ½ in neurons from both WKY rats and SHRs; however, the stimulation was 50% greater in the SHR. Conclusions: The study demonstrates that brain PRR is functional and plays a role in the neural control of cardiovascular functions. This may help resolve a long-held controversy concerning the existence of intrinsic and functional brain RAS.
Implementation of a Statewide System for Coronary Reperfusion for ST-Segment Elevation Myocardial Infarction
Authors: James G Jollis, Mayme L Roettig, Akinyele O Aluko, Kevin J Anstrom, Robert J Applegate, Joseph D Babb, Peter B Berger, David J Bohle, Sidney M Fletcher, J Lee Garvey, William R Hathaway, James W Hoekstra, Robert V Kelly, William T Maddox, Joseph R Shiber, F Scott Valeri, Bradley A Watling, B Hadley Wilson, Christopher B Granger
Journal: JAMA (2007)

Despite 2 decades of evidence demonstrating benefits from prompt coronary reperfusion, registries continue to show that many patients with ST-segment elevation myocardial infarction (STEMI) are treated too slowly or not at all.To establish a statewide system for reperfusion, as exists for trauma care, to overcome systematic barriers.A quality improvement study that examined the change in speed and rate of coronary reperfusion after system implementation in 5 regions in North Carolina involving 65 hospitals and associated emergency medical systems (10 percutaneous coronary intervention [PCI] hospitals and 55 non-PCI hospitals).A total of 1164 patients with STEMI (579 preintervention and 585 postintervention) eligible for reperfusion were treated at PCI hospitals (median age 61 years, 31% women, 4% Killip class III or IV). A total of 925 patients with STEMI (518 preintervention and 407 postintervention) were treated at non-PCI hospitals (median age 62 years, 32% women, 4% Killip class III or IV).Early diagnosis and the most expedient coronary reperfusion method at each point of care: emergency medical systems, emergency department, catheterization laboratory, and transfer. Within 5 regions, PCI hospitals agreed to provide single-call catheterization laboratory activation by emergency medical personnel, accept patients regardless of bed availability, and improve STEMI care for the entire region regardless of hospital affiliation.Reperfusion times and rates 3 months before (July to September 2005) and 3 months after (January to March 2007) a year-long implementation.Median reperfusion times significantly improved according to first door-to-device (presenting to PCI hospital 85 to 74 minutes, P < .001; transferred to PCI hospital 165 to 128 minutes, P < .001), door-to-needle in non-PCI hospitals (35 to 29 minutes, P = .002), and door-in to door-out for patients transferred from non-PCI hospitals (120 to 71 minutes, P < .001). Nonreperfusion rates were unchanged (15%) in non-PCI hospitals and decreased from 23% to 11% in the PCI hospitals. For patients presenting to or transferred to PCI hospitals, clinical outcomes including death, cardiac arrest, and cardiogenic shock did not significantly change following the intervention.A statewide program focused on regional systems for reperfusion for STEMI can significantly improve quality of care. Further research is needed to ensure that programs that result in improved application of reperfusion treatments will lead to reductions in mortality and morbidity from STEMI.
Recombinant γ-interferon as adjuvant to hepatitis B vaccine in hemodialysis patients
Authors: Juan Antonio Quiroga, Inmaculada Castillo, Juan Carlos Porres, Santos Casado, Federico Sáez, María Gracia Martínez, Mariano Gómez, Luis Inglada, Luis Sánchez-Sicilia, Adela Mora, Fernando Galiana, Guillermina Barril, Vicente Carreño
Journal: Hepatology (1990)

Patients undergoing long-term hemodialysis are at high risk of acquiring hepatitis B yet tend to have poor rates of response to hepatitis B vaccine. The effect of recombinant human γ-interferon (2 million units/m2) on the response to a recombinant hepatitis B vaccine was evaluated in a prospective, randomized controlled trial in 81 hemodialysis patients. A similar proportion of both groups of vaccinees ultimately developed antibody to HBsAg including 81% of the 41 recipients of vaccine alone (group I) and 89% of the 40 recipients of vaccine with γ-interferon (group II). However, the antibody to HBsAg response occurred earlier in recipients of vaccine with γ-interferon, so that at 4 mo 63% of group I and 88% of group II had antibody to HBsAg (p < 0.025). Furthermore, titers of antibody to HBsAg tended to be higher in the vaccinees given interferon; the final geometric mean titers were 232 IU/L in group I and 330 IU/L in group II (p = not significant). Retrospective testing for antibody to hepatitis C virus revealed that 21 (26%) hemodialysis patients were seropositive at entry into this trial, but the presence of antibody to hepatitis C virus did not appear to affect the response rate to the hepatitis B vaccine. These results suggest that the effects of γ-interferon as an adjuvant in increasing the response rate to hepatitis B vaccination deserve further evaluation perhaps most appropriately in persons who have not responded to an initial course of vaccine. (HEPATOLOGY 1990;12:661–663).
What oncologists tell patients about survival benefits of palliative chemotherapy and implications for informed consent: qualitative study
Authors: S. Audrey, J. Abel, J. M Blazeby, S. Falk, R. Campbell
Journal: BMJ (2008)

<b>Objective</b> To examine how much oncologists tell patients about the survival benefit of palliative chemotherapy during consultations at which decisions about treatment are made. <b>Design</b> Qualitative study in which consultations were observed and digitally recorded. <b>Setting</b> Teaching hospital and district general hospital in south west England. <b>Participants</b> 37 patients with advanced non-small cell lung cancer (n=12), pancreatic cancer (n=13), and colorectal cancer (n=12); and nine oncologists, including four consultants and five registrars. <b>Main outcome measures</b> All recordings were transcribed completely, anonymised, and electronically coded with ATLAS.ti. Constant comparison was used to identify themes and patterns. The framework method of data management, in which data were charted, was used to aid transparency of interpretation. <b>Results</b> During the consultations, information given to patients about survival benefit included numerical data ("about four weeks"), an idea of timescales ("a few months extra"), vague references ("buy you some time"), or no mention at all. In most consultations (26/37) discussion of survival benefit was vague or non-existent. <b>Conclusions</b> Most patients were not given clear information about the survival gain of palliative chemotherapy. To aid decision making and informed consent, we recommend that oncologists sensitively describe the benefits and limitations of this treatment, including survival gain.
Target all risk factors
Authors: M J Stephen, A M Porter, D J M Keenan
Journal: BMJ (1994)

studies of smoking cessation smokers' activities in attempting to stop smoking should be measured in tandem with more conventional measures of the rate of cessation.4Attempts to stop are associated with the final goal of continuous abstinence.Changes in the number of attempts to stop may thus be more sensitive to intervention than the dichotomous outcome of smoking cessation.This is just one suggestion, and much work is required to validate any new outcome measures.'The results of Cupples and McKnight's study2 suggest, however, that careful consideration of appropriate outcomes is vital to improving our knowledge about how we should approach health promotion.
Cyclin-Dependent Kinase Inhibitor p27 <sup>Kip1</sup> , But Not p21 <sup>WAF1/Cip1</sup> , Is Required for Inhibition of Hypoxia-Induced Pulmonary Hypertension and Remodeling by Heparin in Mice
Authors: Lunyin Yu, Deborah A. Quinn, Hari G. Garg, Charles A. Hales
Journal: Circulation Research (2005)

Heparin has growth inhibitory effects on pulmonary artery smooth muscle cell (PASMC) in vitro and in vivo. However, the mechanism has not been fully defined. In this study, we investigated the role of cyclin-dependent kinase inhibitors, p21 WAF1/cip1 (p21) and p27 Kip1 (p27), in the inhibitory effect of heparin on PASMC proliferation in vitro and on hypoxia-induced pulmonary hypertension in vivo using p21 and p27-null mice. In vitro, loss of the p27 gene negated the inhibitory effect of heparin on PASMC proliferation, but p21 was not critical for this inhibition. In vivo, heparin significantly inhibited the development of hypoxia-induced pulmonary hypertension and remodeling, as evidenced by decreased right ventricular systolic pressure, ratio of right ventricular weight to left ventricle plus septum weight, and percent wall thickness of pulmonary artery, in p21 +/+ , p21 −/− , p27 +/+ , and p27 +/− , but not in p27 −/− mice. We also observed that hypoxia decreased p27 expression significantly in mouse lung, which was restored by heparin. Heparin inhibited Ki67 proliferative index in terminal bronchial vessel walls in p27 +/+ and p27 +/− , but not in p27 −/− mice exposed to hypoxia. Therefore, we conclude that the cyclin-dependent kinase inhibitor p27, but not p21, is required for the inhibition of hypoxic pulmonary vascular remodeling by heparin.
Faecal elastase 1: a novel, highly sensitive, and specific tubeless pancreatic function test.
Authors: C Loser, A Mollgaard, U R Folsch
Journal: Gut (1996)

BACKGROUND: Indirect pancreatic function tests available today are unreliable for clinical practice in early chronic pancreatitis due to their low sensitivity in mild and moderate exocrine pancreatic insufficiency. AIM: To evaluate the sensitivity, specificity, and practicability of faecal elastase 1 determination in patients with mild, moderate, and severe exocrine pancreatic insufficiency categorised according to the secretin-caerulein test as "gold standard9. PATIENTS AND METHODS: Faecal and duodenal elastase 1 concentration (commercial enzyme linked immunosorbent assay (ELISA)), faecal chymotrypsin activity, faecal fat analysis, and the secretin-caerulein test were performed on 44 patients with mild (n = 8), moderate (n = 14), and severe (n = 22) exocrine pancreatic insufficiency and 35 patients with gastrointestinal diseases of non-pancreatic origin. Fifty healthy volunteers were studied as normal controls. Morphological examinations were carried out to definitely confirm or exclude chronic pancreatitis. RESULTS: With a cut off of 200 micrograms elastase 1/g stool the sensitivity was 63% for mild, 100% for moderate, 100% for severe, and 93% for all patients with exocrine pancreatic insufficiency, and specificity was 93%. Values for chymotrypsin were 64% (sensitivity) and 89% (specificity). Significant (p &lt; 0.001) correlations were found for faecal and duodenal elastase with duodenal lipase, amylase, trypsin, volume, and bicarbonate output. Individual day to day variations of faecal elastase 1 concentrations were very low (mean CV = 15%) and sample storage at room temperature is possible for at least one week. CONCLUSIONS: Faecal elastase 1 determination proved to be a highly sensitive and specific tubeless pancreatic function test.
Cultural Barriers to Effective Medical Care Among Indochinese Patients
Authors: G N Hoang, R V Erickson
Journal: Annual Review of Medicine (1985)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Beneficial effects of propionyl ?-carnitine on sarcolemmal changes in congestive heart failure due to myocardial infarction
Authors: R Sethi
Journal: Cardiovascular Research (1999)

Objective: Earlier studies have revealed sarcolemmal (SL) defects in congestive heart failure due to myocardial infarction; however, the mechanisms of SL changes in the failing heart are poorly understood. Since congestive heart failure is associated with various metabolic abnormalities including a deficiency of carnitine, we examined the effects of propionyl l-carnitine, a carnitine derivative, in animals with congestive heart failure. Methods: For this purpose, heart failure in rats was induced by occluding the coronary artery and 3 weeks later the animals were treated with 100 mg/kg (i.p. daily) propionyl l-carnitine for 4 weeks. The sham control group received saline injections. The animals were assessed for their left ventricular function. SL membranes were examined for Na+–K+ ATPase, Na+–Ca2+ exchange and adenylate cyclase activities. Results: A marked improvement in the attenuated left ventricular function of the experimental animals was seen upon treatment with propionyl l-carnitine. The SL adenylyl cyclase activities in control, untreated failing hearts and treated failing hearts were 590±36, 190±22 and 320±21 pmol cAMP/mg/10 min, whereas the SL Na+–K+ ATPase activities were 35.7±2.8, 22.5±2.4 and 30.1±2.8 μmol Pi/mg/h, respectively. Furthermore, the SL Na+-dependent Ca2+-uptake activity, which decreased in the failing hearts (4.6±0.4 vs. 9.3±0.7 nmol Ca2+/mg/2 s for control), was improved (6.8±0.5 nmol Ca2+/mg/2 s) significantly following treatment with propionyl l-carnitine. Conclusion: These results indicate that metabolic therapy with propionyl l-carnitine may attenuate defects in the SL membrane and thus may improve heart function in congestive heart failure due to myocardial infarction.
Functionalization of multilayered DNA-coatings with bone morphogenetic protein 2
Authors: J.J.J.P. van den Beucken, X.F. Walboomers, O.C. Boerman, M.R.J. Vos, N.A.J.M. Sommerdijk, T. Hayakawa, T. Fukushima, Y. Okahata, R.J.M. Nolte, J.A. Jansen
Journal: Journal of Controlled Release (2006)
First Site of Failure Analysis Incompletely Addresses Issues of Late and Unexpected Metastases in p16-Positive Oropharyngeal Cancer
Authors: Brian O'Sullivan, David L. Adelstein, Shao Hui Huang, Shlomo A. Koyfman, Wade Thorstad, Andrew J. Hope, James S. Lewis, Brian Nussenbaum
Journal: Journal of Clinical Oncology (2015)
Identification of Nicotinamide<i>N</i>-Methyltransferase as a Novel Serum Tumor Marker for Colorectal Cancer
Authors: Markus Roeßler, Wolfgang Rollinger, Stefan Palme, Marie-Luise Hagmann, Peter Berndt, Alfred M. Engel, Bernd Schneidinger, Michael Pfeffer, Herbert Andres, Johann Karl, Heinz Bodenmüller, Josef Rüschoff, Thomas Henkel, Gerhard Rohr, Siegbert Rossol, Wolfgang Rösch, Hanno Langen, Werner Zolg, Michael Tacke
Journal: Clinical Cancer Research (2005)

The goal of this study was to identify and validate novel serum markers of human colorectal cancer as potential candidates for noninvasive detection of early colorectal neoplasm.Employing two-dimensional gel electrophoresis and mass spectrometry, we analyzed 16 matched colorectal cancer and adjacent normal tissue samples. Proteins found to be elevated in cancer tissue were further validated by generating antibodies which were used for immunoblotting of tissue samples and for the development of highly sensitive immunoassays for assessment of serum samples.In total, 735 different proteins were identified in colon tissue. Strong elevation in colorectal cancer for five proteins was confirmed by immunoblot analysis: transforming growth factor-beta induced protein ig-h3 (betaIG-H3), nicotinamide N-methyltransferase (NNMT), nucleoside diphosphate kinase A (nm23-H1), purine nucleoside phosphorylase (PNPH), and mannose-6-phosphate receptor binding protein 1 (M6P1). Elevated levels of NNMT, which is not predicted to be secreted but is known as a cytoplasmic protein, were found in serum from patients with colorectal cancer. Employing a receiver-operating characteristic curve based on the measurement of 109 patients with colorectal cancer and 317 healthy controls, we obtained an area under the curve of 0.84 for NNMT, which was superior to the established tumor marker carcinoembryogenic antigen with an area under the curve of 0.78.It is proposed that NNMT serum levels may have significance in the early detection and in the management of patients with colorectal cancer.
Metalloproteinase-9 deficiency protects against hepatic ischemia/reperfusion injury
Authors: Takashi Hamada, Constantino Fondevila, Ronald W. Busuttil, Ana J. Coito
Journal: Hepatology (2007)

Leukocyte transmigration across endothelial and extracellular matrix protein barriers is dependent on adhesion and focal matrix degradation events. In the present study we investigated the role of metalloproteinase-9 (MMP-9/gelatinase B) in liver ischemia/reperfusion (I/R) injury using MMP-9-deficient (MMP-9−/−) animals and mice treated with a specific anti-MMP-9 neutralizing antibody or with a broad gelatinase inhibitor for both MMP-9 and metalloproteinase-2 (MMP-2/gelatinase A). Compared to wild-type mice, MMP-9−/− mice and mice treated with an anti-MMP-9 antibody showed significantly reduced liver damage. In contrast, mice treated with a broad gelatinase inhibitor showed rather inferior protection against I/R injury and were characterized by persistent ongoing liver inflammation, suggesting that MMP-2 and MMP-9 may have distinct roles in this type of injury. MMP-9 was mostly detected in Ly-6G and macrophage antigen–1 leukocytes adherent to the vessel walls and infiltrating the damaged livers of wild-type mice after liver I/R injury. Leukocyte traffic and cytokine expression were markedly impaired in livers of MMP-9−/− animals and in livers of mice treated with anti-MMP-9 antibody after I/R injury; however, initiation of the endothelial adhesion cascades was similar in both MMP-9−/− and control livers. We also showed that MMP-9-specific inhibition disrupted neutrophil migration across fibronectin in transwell filters and depressed myeloperoxidase (MPO) activation in vitro. Conclusion: These results support critical functions for MMP-9 in leukocyte recruitment and activation leading to liver damage. Moreover, they provide the rationale for identifying inhibitors to specifically target MMP-9 in vivo as a potential therapeutic approach in liver I/R injury. (Hepatology 2007.)