tbuckley/cabot-search huggingface dataset:
Life expectancy in osteogenesis imperfecta
Authors: C. R Paterson, S. A Ogston, R. M Henry
Journal: BMJ (1996)

No information is available on life expectancy in osteogenesis imperfecta; it is often assumed that this is impaired. In a recent review this is described as a severe disease in which “some patients reach adulthood.”1 We were stimulated by requests for information for a patient told by an insurer that compensation would be reduced because of “poor life expectancy,” and for an affected child who wished to claim from her father's estate. We sought to obtain reliable figures for life expectancy from our large survey of patients with osteogenesis imperfecta.2

We limited our survey to patients in England and Wales. Patients were excluded if they could not, with confidence, be assigned to one of the Sillence types,3 or if they had the perinatal lethal form (type II). Patients identified …
Prolonged fever after pleural instillation of Corynebacterium parvum (Coparvax).
Authors: C M Laroche, M Britton
Journal: Thorax (1987)

Coparvax is a formalin killed freeze dried preparation of Corynebacterium parvum, used to prevent reaccumulation of malignant effusions when instilled into the pleural cavity.Side effects are usually reported as being mild and transient.We report three patients who experienced a more prolonged reaction than any previously reported. Case reports CASE I
Inhibition of rat arterial smooth muscle cell proliferation by heparin. II. In vitro studies.
Authors: R L Hoover, R Rosenberg, W Haering, M J Karnovsky
Journal: Circulation Research (1980)

We studied in vitro the effects heparin on the growth of rat aortic smooth muscle cells. Measurements of growth were monitored by [3H]thymidine uptake and changes in cell number over a period of 3 days. Our results show that heparin-highly anticoagulant or nonanticoagulant-significantly inhibits growth of smooth muscle cells. We also show that this is a highly specfic interaction with regard to molecule and cell type: i.e., other polyanions, except for a low molecular weight dextran sulfate, do not have the same effect on growth, and not all cells are inhibited by heparin; e.g., endothelial cell growth actually is enhanced. After removing antithrombin from our media, we carried out experiments which show that heparin is effective even though thrombin, a potent mitogenic agent, is still present and active. We also found that passing the platelet extract over a heparin column did not remove all of the motogenic activity of the platelet preparation. Both experiments indicate an inhibitory role for the heparin molecule, per se. Our results support the findings of a recent paper (Guyton et al., 1980) showing that heparin can limit the size of myointimal plaques in rats after carotid injuries by inhibiting smooth muscle cell proliferation.
Evaluation of Creatine Analogues as a New Class of Anticancer Agents Using Freshly Explanted Human Tumor Cells
Authors: K. J. Martin, S.-F. Chen, G. M. Clark, D. Degen, M. Wajima, D. D. Von Hoff, R. Kaddurah-Daouk
Journal: JNCI Journal of the National Cancer Institute (1994)

The creatine kinase (CK) isozymes and their substrates, creatine and creatine phosphate, are believed to play a pivotal role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, and brain. This enzyme system may also be involved in the process of cellular transformation. Inhibition of tumor cell growth by creatine analogues has been observed and may be due to the ability of these analogues to impair cellular energy generation and utilization.An in vitro human tumor colony-forming assay was used to predict the clinical usefulness of creatine analogues as anticancer agents.The ability of cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) and homocyclocreatine (1-carboxyethyl-2-iminoimidazolidine) to inhibit the growth of cells prepared from tumor samples taken directly from patients was evaluated by quantitative measurement of colony formation in a soft-agar cell culture assay system. Cyclocreatine was tested in this human tumor colony-forming assay at concentrations ranging from 0.067 to 20 mM against 128 tumor samples, 51 of which formed colonies in the assay and were considered evaluable. Homocyclocreatine was similarly tested at concentrations from 0.2 to 20 mM against 139 tumor samples; 54 were considered evaluable. The colony-forming assay was also used to compare the efficacy of the creatine analogues to representatives from the six major classes of standard chemotherapeutics (alkylating agents, antimetabolites, DNA intercalators, platinum compounds, topoisomerase inhibitors, and tubulin-interacting agents). In addition, CK levels were measured in 192 tumor samples that were taken from 166 patients.Cyclocreatine and homocyclocreatine, at concentrations previously achieved in animal tissues (7-20 mM), had antitumor activity against 19% and 50%, respectively, of tumor samples that formed colonies in the assay. Cyclocreatine was effective against a subset of tumors sensitive to homocyclocreatine (P = .023; Fisher's exact test), which was the more potent creatine analogue in this assay (P < .001; McNemar's test). No relationships were seen between tumor samples sensitive to the creatine analogues and those sensitive to standard chemotherapeutics. Pairwise Wilcoxon rank sum tests indicated that CK activity was significantly higher in tumors with any growth in the colony assay compared with tumors that did not grow (P < .025).The creatine analogues, cyclocreatine and homocyclocreatine, effectively reduced colony formation of freshly explanted human tumor cells. The mechanism of action or resistance to these compounds seems to differ from those of standard chemotherapeutics.Creatine analogues that may alter the energy status of the tumor cell potentially represent promising new anticancer agents that function through a unique mechanism.
Response criteria for rheumatoid arthritis in clinical practice: how useful are they?
Authors: A Gulfe
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To compare the performance of the American College of Rheumatology (ACR), European League Against Rheumatism (EULAR), and simple disease activity index (SDAI) response criteria for rheumatoid arthritis at the individual level in an observational cohort. <b>Methods:</b> 184 outpatients were followed using a structured protocol. For each patient, the responses according to ACR 20% and 50%, EULAR moderate and good, and SDAI minor and major responses were calculated. For comparison, improvements in health assessment questionnaire (HAQ) score of 0.22 and 0.5 were calculated. The numbers of individuals fulfilling the criteria at each level were compared, and the numbers fulfilling any two sets of response criteria calculated. The EULAR "moderate" and "good" responses were grouped together as "overall," and SDAI "minor" and "major" were merged into SDAI "overall". <b>Results:</b> All 94 ACR 20 responders were found in the EULAR and SDAI "overall" response groups, and 118 of 124 SDAI "overall" responders were found in the EULAR "overall" group. In contrast, of 53 ACR 50 responders, only 34 were found in the EULAR "good" or SDAI "major" group. Among the 56 patients in the EULAR "good" response group, only 26 met the SDAI "major" response. Improvement in HAQ score performed similarly to the other response criteria sets at the group levels. <b>Conclusions:</b> For individual patients, agreement is good at the level of ACR 20 response, when EULAR overall, SDAI overall, or HAQ 0.22 criteria are applied. Agreement between ACR 50, EULAR good, SDAI major, and HAQ 0.5 response is poor. This should be considered when response criteria are used for clinical decisions.
Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years
Authors: Christopher J.D. McKinlay, Jane M. Alsweiler, Judith M. Ansell, Nicola S. Anstice, J. Geoffrey Chase, Gregory D. Gamble, Deborah L. Harris, Robert J. Jacobs, Yannan Jiang, Nabin Paudel, Matthew Signal, Benjamin Thompson, Trecia A. Wouldes, Tzu-Ying Yu, Jane E. Harding
Journal: New England Journal of Medicine (2015)

Neonatal hypoglycemia is common and can cause neurologic impairment, but evidence supporting thresholds for intervention is limited.We performed a prospective cohort study involving 528 neonates with a gestational age of at least 35 weeks who were considered to be at risk for hypoglycemia; all were treated to maintain a blood glucose concentration of at least 47 mg per deciliter (2.6 mmol per liter). We intermittently measured blood glucose for up to 7 days. We continuously monitored interstitial glucose concentrations, which were masked to clinical staff. Assessment at 2 years included Bayley Scales of Infant Development III and tests of executive and visual function.Of 614 children, 528 were eligible, and 404 (77% of eligible children) were assessed; 216 children (53%) had neonatal hypoglycemia (blood glucose concentration, <47 mg per deciliter). Hypoglycemia, when treated to maintain a blood glucose concentration of at least 47 mg per deciliter, was not associated with an increased risk of the primary outcomes of neurosensory impairment (risk ratio, 0.95; 95% confidence interval [CI], 0.75 to 1.20; P=0.67) and processing difficulty, defined as an executive-function score or motion coherence threshold that was more than 1.5 SD from the mean (risk ratio, 0.92; 95% CI, 0.56 to 1.51; P=0.74). Risks were not increased among children with unrecognized hypoglycemia (a low interstitial glucose concentration only). The lowest blood glucose concentration, number of hypoglycemic episodes and events, and negative interstitial increment (area above the interstitial glucose concentration curve and below 47 mg per deciliter) also did not predict the outcome.In this cohort, neonatal hypoglycemia was not associated with an adverse neurologic outcome when treatment was provided to maintain a blood glucose concentration of at least 47 mg per deciliter. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).
International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin).
Authors: D Hoyer, D E Clarke, J R Fozard, P R Hartig, G R Martin, E J Mylecharane, P R Saxena, P P Humphrey
Journal: Pharmacological Reviews (1994)

It is evident that in the last decade or so, a vast amount of new information has become available concerning the various 5-HT receptor types and their characteristics. This derives from two main research approaches, operational pharmacology, using selective ligands (both agonists and antagonists), and, more recently, molecular biology. Although the scientific community continues to deliberate about the hierarchy of criteria for neurotransmitter receptor characterisation, there seems good agreement between the two approaches regarding 5-HT receptor classification. In addition, the information regarding transduction mechanisms and second messengers is also entirely consistent. Thus, on the basis of these essential criteria for receptor characterisation and classification, there are at least three main groups or classes of 5-HT receptor: 5-HT1, 5-HT2, and 5-HT3. Each group is not only operationally but also structurally distinct, with each receptor group having its own distinct transducing system. The more recently identified 5-HT4 receptor almost undoubtedly represents a fourth 5-HT receptor class on the basis of operational and transductional data, but this will only be definitively shown when the cDNA for the receptor has been cloned and the amino acid sequence of the protein is known. Although those 5-HT receptors that have been fully characterised and classified to date (and, hence, named with confidence) would seem to mediate the majority of the actions of 5-HT throughout the mammalian body, not all receptors for 5-HT are fully encompassed within our scheme of classification. These apparent anomalies must be recognised and need further study. They may or may not represent new groups of 5-HT receptor or subtypes of already known groups of 5-HT receptor. Even though the cDNAs for the 5-ht1E, 5-ht1F, 5-ht5, 5-ht6, and 5-ht7 receptors have been cloned and their amino acid sequence defined, more data are necessary concerning their operational and transductional characteristics before one can be confident of the suitability of their appellations. Therefore, it is important to rationalise in concert all of the available data from studies involving both operational approaches of the classical pharmacological type and those from molecular and cellular biology.(ABSTRACT TRUNCATED AT 400 WORDS)
THE CRESCENDO MURMUR OF MITRAL STENOSIS
Authors: E. M. Brockbank
Journal: BMJ (1909)

A--. 28 .10I50 but merely that lymph bas transuded from the vessels, and in this lymph there.is a considerable number of' 4:mphoeyts-, probably obtained from the tissues as well Os from the capillaries.There is no doubt a digestion.4eucocytosis, but it, -is not what has been usua,lly Aesoribed.BATHS.
Effect of Adrenergic Stimulation on Action Potential Duration Restitution in Humans
Authors: Peter Taggart, Peter Sutton, Zaid Chalabi, Mark R. Boyett, Ron Simon, Donna Elliott, Jaswinder S. Gill
Journal: Circulation (2003)

Background— Enhanced sympathetic activity facilitates complex ventricular arrhythmias and fibrillation. The restitution properties of action potential duration (APD) are important determinants of electrical stability in the myocardium. Steepening of the slope of APD restitution has been shown to promote wave break and ventricular fibrillation. The effect of adrenergic stimulation on APD restitution in humans is unknown. Methods and Results— Monophasic action potentials were recorded from the right ventricular septum in 18 patients. Standard APD restitution curves were constructed at 3 basic drive cycle lengths (CLs) of 600, 500, and 400 ms under resting conditions and during infusion of isoprenaline (15 patients) or adrenaline (3 patients). The maximum slope of the restitution curves was measured by piecewise linear regression segments of sequential 40-ms ranges of diastolic intervals in steps of 10 ms. Under control conditions, the maximum slope was steeper at longer basic CLs; eg, mean values for the maximum slope were 1.053±0.092 at CL 600 ms and 0.711±0.049 at CL 400 ms (±SEM). Isoprenaline increased the steepness of the maximum slope of APD restitution, eg, from a maximum slope of 0.923±0.058 to a maximum slope of 1.202±0.121 at CL 500 ms. The effect of isoprenaline was greater at the shorter basic CLs. A similar overall effect was observed with adrenaline. Conclusions— The adrenergic agonists isoprenaline and adrenaline increased the steepness of the slope of the APD restitution curve in humans over a wide range of diastolic intervals. These results may relate to the known effects of adrenergic stimulation in facilitating ventricular fibrillation.
Near-threshold field stimulation: Intramural versus surface activation
Authors: C ZEMLIN, S MIRONOV, A PERTSOV
Journal: Cardiovascular Research (2005)

Objective: The mechanism by which an electric field terminates arrhythmias continues to puzzle investigators. Existing experimental methods provide information about epicardial manifestations of electrical cardioversion, yet little is known about field effects deep inside the myocardium. Here we combine specially designed optical mapping experiments and computer modeling to separate the intra-myocardial and surface field effects. Methods: We used isolated coronary perfused and superfused slabs of pig right ventricular wall (n=6) stained with di-4-ANNEPS. A uniform transmural field was produced via two parallel planar (5 × 5 cm) transparent mesh electrodes aligned with the endocardial and epicardial surfaces. Low-intensity shocks (≥ 3.3 V/cm) were applied during diastole. The electrical activity under both electrodes was recorded simultaneously using two CCD cameras at 800 frames/s. Shock responses were also simulated using a bidomain Luo–Rudy model. Results: We discovered that during the near-threshold diastolic field stimulation, when surface polarization should be dominant, the early activation occurs not at the cathodal surface, as might be expected, but deep inside the myocardium. Comparison of epi- and endocardial activation delays suggests that the sites of early activation are located closer to the endocardium. Our experimental observations could be reproduced computationally by assuming large resistive heterogeneities inside the myocardial wall. Conclusions: Surface polarization plays a minor role during field stimulation. Intramural virtual electrodes produced even by weak fields are sufficiently strong to initiate intra-myocardial excitation. Significant heterogeneities in tissue resistivity may explain the strength of the virtual electrodes.
Highly temperature-sensitive liposomes based on a thermosensitive block copolymer for tumor-specific chemotherapy
Authors: Kenji Kono, Toshiaki Ozawa, Tomohide Yoshida, Fuminori Ozaki, Yukihito Ishizaka, Kazuo Maruyama, Chie Kojima, Atsushi Harada, Sadahito Aoshima
Journal: Biomaterials (2010)
Sonic Hedgehog Paracrine Signaling Activates Stromal Cells to Promote Perineural Invasion in Pancreatic Cancer
Authors: Xuqi Li, Zheng Wang, Qingyong Ma, Qinhong Xu, Han Liu, Wanxing Duan, Jianjun Lei, Jiguang Ma, Xiu Wang, Shifang Lv, Liang Han, Wei Li, Jian Guo, Kun Guo, Dong Zhang, Erxi Wu, Keping Xie
Journal: Clinical Cancer Research (2014)

Pancreatic cancer is characterized by stromal desmoplasia and perineural invasion (PNI). We sought to explore the contribution of pancreatic stellate cells (PSC) activated by paracrine Sonic Hedgehog (SHH) in pancreatic cancer PNI and progression.In this study, the expression dynamics of SHH were examined via immunohistochemistry, real-time PCR, and Western blot analysis in a cohort of carcinomatous and nonneoplastic pancreatic tissues and cells. A series of in vivo and in vitro assays was performed to elucidate the contribution of PSCs activated by paracrine SHH signaling in pancreatic cancer PNI and progression.We show that SHH overexpression in tumor cells is involved in PNI in pancreatic cancer and is an important marker of biologic activity of pancreatic cancer. Moreover, the overexpression of SHH in tumor cells activates the hedgehog pathway in PSCs in the stroma instead of activating tumor cells. These activated PSCs are essential for the promotion of pancreatic cancer cell migration along nerve axons and nerve outgrowth to pancreatic cancer cell colonies in an in vitro three-dimensional model of nerve invasion in cancer. Furthermore, the coimplantation of PSCs activated by paracrine SHH induced tumor cell invasion of the trunk and nerve dysfunction along sciatic nerves and also promoted orthotropic xenograft tumor growth, metastasis, and PNI in in vivo models.These results establish that stromal PSCs activated by SHH paracrine signaling in pancreatic cancer cells secrete high levels of PNI-associated molecules to promote PNI in pancreatic cancer.
IT-25 * DEVELOPMENTALLY REGULATED ANTIGENS FOR IMMUNOLOGIC TARGETING OF MEDULLOBLASTOMA SUBTYPES
Authors: C. Pham, C. Flores, Y. Pei, R. Wechsler-Reya, D. Mitchell
Journal: Neuro-Oncology (2014)

INTRODUCTION: Medulloblastoma (MB) remains incurable in one third of patients despite aggressive multi-modality standard therapies. Immunotherapy presents a promising alternative by specifically targeting cancer cells. To date, there have been no successful immunologic applications targeting MB. Emerging evidence from integrated genomic studies has suggested MB variants arise from deregulation of pathways affecting proliferation of progenitor cell populations within the developing cerebellum. Using total embryonic RNA as a source of tumor rejection antigens is attractive because it can be delivered as a single vaccine, target both known and unknown fetal proteins, and can be refined to preferentially treat distinct MB subtypes. METHODS: We have created two transplantable, syngeneic animal MB models recapitulating human SHH and Group 3 variants to investigate the immunologic targeting of different MB subtypes. We generated T cells specific to the developing mouse cerebellum (P5) and tested their reactivity to target cells pulsed with total RNA from two MB subtypes and the normal brain. Immune responses were evaluated by measuring cytokine secretion following re-stimulation of activated T cells with both normal and tumor cell targets. In vivo antitumor efficacy was also tested in survival studies of intracranial tumor-bearing animals. RESULTS: We generated T cells specific to the developing cerebellum in vitro, confirming the immunogenicity of developmentally regulated antigens. Additionally, we have shown that developmental antigen-specific T cells produce high levels of Th1-type cytokines in response to tumor cells of two immunologically distinct subtypes of MB. Interestingly, developmental antigen specific T cells do not show cross reactivity with the normal brain or subsequent stages of the developing brain after P5. Targeting developmental antigens also conferred a significant survival benefit in a treatment model of Group 3 tumor bearing animals. CONCLUSIONS: Developmental antigens can safely target multiple MB subtypes with equal effectiveness compared to previously established total tumor strategies.
Cyclin-Dependent Kinase 2 Functions in Normal DNA Repair and Is a Therapeutic Target in BRCA1-Deficient Cancers
Authors: Andrew J. Deans, Kum Kum Khanna, Carolyn J. McNees, Ciro Mercurio, Jörg Heierhorst, Grant A. McArthur
Journal: Cancer Research (2006)

Abstract Abnormal regulation of progression from G1 to S phase of the cell cycle by altered activity of cyclin-dependent kinases (CDKs) is a hallmark of cancer. However, inhibition of CDKs, particularly CDK2, has not shown selective activity against most cancer cells because the kinase seems to be redundant in control of cell cycle progression. Here, we show a novel role in the DNA damage response and application of CDK inhibitors in checkpoint-deficient cells. CDK2−/− mouse fibroblasts and small interfering RNA–mediated or small-molecule–mediated CDK2 inhibition in MCF7 or U2OS cells lead to delayed damage signaling through Chk1, p53, and Rad51. This coincided with reduced DNA repair using the single-cell comet assay and defects observed in both homologous recombination and nonhomologous end-joining in cell-based assays. Furthermore, tumor cells lacking cancer predisposition genes BRCA1 or ATM are 2- to 4-fold more sensitive to CDK inhibitors. These data suggest that inhibitors of CDK2 can be applied to selectively enhance responses of cancer cells to DNA-damaging agents, such as cytotoxic chemotherapy and radiotherapy. Moreover, inhibitors of CDKs may be useful therapeutics in cancers with defects in DNA repair, such as mutations in the familial breast cancer gene BRCA1. (Cancer Res 2006; 66(16): 8219-26)