tbuckley/cabot-search huggingface dataset:
Thrombolytic effects of recombinant fibrolase or APSAC in a canine model of carotid artery thrombosis.
Authors: F S Markland, G S Friedrichs, S R Pewitt, B R Lucchesi
Journal: Circulation (1994)

BACKGROUND Thrombolytic agents used clinically rely on the activation of plasminogen to plasmin. Plasmin possesses multiple actions including increasing thrombin activity and activation of platelets. Thus, after successful thrombolytic therapy, arterial hyperactivity and reocclusion may be the result of a predominant plasmin-induced thrombogenic action at the site of the residual thrombus. Fibrolase, a direct-acting fibrinolytic enzyme from southern copperhead snake venom, induces rapid clot lysis in vitro. Fibrolase does not rely on plasminogen activation or any other bloodborne components for activity and is not inhibited by any of the rapidly acting serine proteinase inhibitors in blood. METHODS AND RESULTS We investigated the efficacy of fibrolase to lyse an occlusive thrombus formed in the carotid artery of the anesthetized dog. Electrolytic injury was initiated in both the right and left carotid arteries. Thirty minutes after both arteries were occluded, each vessel was infused with either fibrolase (4 mg/kg over 5 minutes) or physiological saline (over 5 minutes). In two separate groups of dogs, anisoylated plasminogen streptokinase activator complex (APSAC) (0.1 U/kg) was infused into the occluded vessel. In the artery infused with fibrolase, five of five dogs exhibited patency within 6 +/- 1 minutes of the infusion (P &lt; .05 versus vehicle-treated artery; Fisher's exact test). In the contralateral carotid artery that received vehicle, the occlusion was maintained throughout the experimental protocol. APSAC alone lysed the thrombus in each vessel within 17 +/- 3 minutes. Five minutes after the end of fibrolase administration and in one of the groups administered APSAC, a glycoprotein (GP)IIb/IIIa antibody, 7E3 (0.8 mg/kg IV), was administered to prevent reocclusion of the patent artery. After 7E3 administration, the vessel treated with fibrolase remained patent in four of five dogs, and six of six APSAC-treated vessels were patent for the remainder of the observation period (2 hours). CONCLUSIONS These studies demonstrate that local administration of fibrolase lyses a carotid arterial thrombus rapidly without excessive hemorrhage or hemodynamic compromise. The enzyme in combination with antiplatelet therapy (7E3) offers a unique mechanism for clot dissolution and may prove useful as a clinically efficacious alternative to presently used thrombolytic agents or may act in a synergistic manner with plasminogen activators.
Nasal obstruction in babies.
Authors: J O Lawson
Journal: BMJ (1969)

sibility if any excessive demand is made on the cardiovascular system at some future date.One thing is probably certain, and that is that no resuscitation of any type would have been effective in restoring a heart with a myocar- dium exhausted after exposure to a large overdose of metabolites.-Iam, etc., Coppenhall,
Social Case-work in General Practice: An Alternative Approach
Authors: L. Ratoff, B. Pearson
Journal: BMJ (1970)

During a two-year period a senior case-worker was seconded by a voluntary family case-work agency, the Liverpool Personal Service Society, to work with three general practitioners. The commonest reasons for referral of the 157 new patients to the social worker over this study period were extreme poverty; housing, matrimonial, and psychiatric problems; and problems of fatherless families. The successful and valuable co-operation between the general practitioners, case-worker, and various specialist professional and financial services of the Society have proved that a professional social worker has an important role in the general-practice team.
Humans should be individualistic and utility-maximizing, but not necessarily “rational”
Authors: Pat Barclay, Martin Daly
Journal: Behavioral and Brain Sciences (2003)

One reason why humans don't behave according to standard game theoretical rationality is because it's not realistic to assume that everyone else is behaving rationally. An individual is expected to have psychological mechanisms that function to maximize his/her long-term payoffs in a world of potentially “irrational” individuals. Psychological decision theory has to be individualistic because individuals make decisions, not groups.
Paget's Disease of the Sternum Simulating an Ectopic Adenoma on Parathyroid Scintigraphy
Authors: RICHARD SEYMOUR, JOHN REES, ANOOP K. SHARMA, MALCOLM H. WHEELER
Journal: Clinical Nuclear Medicine (1997)

The authors present the case of a patient with recurrent hyperparathyroidism who was shown on thallium-technetium subtraction scintigraphy, ultrasound, and magnetic resonance imaging to have recurrent parathyroid tissue in the right side of the neck. The thallium scan also showed intense uptake centrally in the chest, mimicking an intrathoracic adenoma. This was subsequently shown on plain films and a radionuclide bone scan to be due to Paget's disease of the sternum. This case illustrates the value of a combined imaging strategy in preventing an unnecessary thoracotomy after a false-positive nuclear medicine scan.
Principles of Nidotherapy in the Treatment of Persistent Mental and Personality Disorders
Authors: Peter Tyrer, Tom Sensky, Sarah Mitchard
Journal: Psychotherapy and Psychosomatics (2003)

&lt;i&gt;Background:&lt;/i&gt; The principles of a psychological intervention for psychiatric disorders, nidotherapy, are described following its use in the treatment of patients with severe mental illness, most of whom also have personality disorders. Nidotherapy is the collaborative systematic assessment and modification of the environment to minimise the impact of any form of mental disorder on the individual or on society. It is particularly appropriate to consider for chronic and recurring disorders in which there is no prospect of short-term improvement. &lt;i&gt;Methods:&lt;/i&gt; An analysis of the treatment suggests its main tenets are the development of a joint consensus (collateral collocation) of environmental change needed, formulation of targets, consequent monitoring and adjustments made to test the effectiveness of intervention, and a joint structure (arbitrage solving) to adjudicate when changes are considered feasible or impractical by one party and not the other. &lt;i&gt;Results:&lt;/i&gt; Case vignettes are used to describe the main features of the treatment. Although nidotherapy includes some of the elements of cognitive, occupational and family therapy, and even social work, it is different in that it focuses on changing the environment, not the person. It is therefore much more acceptable to those patients who have repeatedly challenged the justification of conventional therapy for their conditions. &lt;i&gt;Conclusions:&lt;/i&gt; Nidotherapy deserves further enquiry as a useful addition to existing psychological treatments.
Expression and Targeting of Interleukin-4 Receptor for Primary and Advanced Ovarian Cancer Therapy
Authors: Mitomu Kioi, Satoru Takahashi, Mariko Kawakami, Koji Kawakami, Robert J. Kreitman, Raj K. Puri
Journal: Cancer Research (2005)

Abstract Because the most characteristic property of ovarian cancer is i.p. spread, the majority of patients are diagnosed at an advanced stage, leading to limited availability of options for curative therapies. With an intent to identify targeted therapeutic approaches, we have observed that ∼60% of 21 ovarian cancer tissue samples express a high density of interleukin-4 receptor (IL-4R), whereas normal ovarian tissues tested (n = 7) expressed no or low levels of IL-4R. To target IL-4R, we have developed IL-4 cytotoxin, in which circular-permuted IL-4 is fused to a mutated form of Pseudomonas exotoxin. This cytotoxin is specifically and highly cytotoxic to PA-1, IGROV-1, and SK-OV3 ovarian carcinoma cell lines in vitro. In addition, it shows remarkable antitumor activities against established s.c. ovarian tumors in immunodeficient animals. i.p. administration of IL-4 cytotoxin in mice with orthotopically implanted ovarian tumors caused regression of established tumors and prevented these animals from tumor metastasis. Continuous i.p. infusion of IL-4 cytotoxin prolonged survival of tumor-bearing mice even with bulky disease. These results indicate that IL-4R–targeted cytotoxin may be a useful agent for the management of patients with ovarian cancer, and further studies need to be done to evaluate its safety, tolerability, and efficacy.
Abstract 4160: Evaluating epithelial-to-mesenchymal transition (EMT) in the EL1-luc/EL1-SV40 T-antigen transgenic mouse model of pancreatic cancer
Authors: Maryland Rosenfeld Franklin, Joseph Krueger, G. David Young, Regina Sennello, Lisa Leary, Shaobin Zhong, Hao Chen, Ed Lim, Ning Zhang, Peter Lassota, Robert Wild
Journal: Cancer Research (2010)

Abstract Epithelial-to-mesenchymal transition (EMT) is a biological function important in normal cellular processes such as embryonic development and wound healing. In cancer it is thought that the tumor cell machinery can re-activate these normal pathways resulting in more aggressive and invasive tumors. The loss of E-cadherin and the gain of vimentin are hallmarks which identify the process of EMT and have been shown to correlate with poor prognosis in multiple solid tumor types. While many preclinical models are utilized to evaluate mechanisms of tumorigenesis few in vivo models evaluating parameters of EMT have been described. The EL1-luc/EL1-SV40 T-antigen transgenic mouse represents a model of pancreatic cancer whereby mice develop tissue specific, spontaneous and bioluminescent pancreatic tumors. To evaluate whether EMT occurs in the EL1-luc/EL1-SV40 T-antigen model in vivo, we collected primary pancreatic tissue from male mice between 10 and 21 weeks of age. The tissue was formalin fixed, paraffin embedded and then utilized for histopathological endpoints such as Hemotoxylin and Eosin staining as well as immunohistochemistry for markers known to be involved in EMT such as E-cadherin and vimentin. We found the tumors to express both markers and become very heterogeneous over time. In early tumors E-cadherin expression is membrane localized and very high. Over time there are areas of the tumors that have reduced or lost E-cadherin expression. Vimentin expression was highly variable but when present tended to be highly expressed. In many of the later stage tumors there was substantial heterogeneity reflected by the appearance of multiple cell types within a tumor. We utilized the Aperio (Aperio Technologies, Vista, CA) slide scanner and software system to evaluate serial sections of tumor samples and found that in some sections of the tumor E-cadherin is present and vimentin is absent, whereas in other areas of the tumor vimentin is present in the absence of E-cadherin. Additionally, we identified areas of the tumor that seem to be expressing both markers which suggests that the EL1-luc/EL1-SV40 T-antigen transgenic mouse may recapitulate many aspects of EMT observed in vivo, thus offering a model system to study the signaling and molecular changes necessary for this process during cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4160.
Association between Influenza during Pregnancy and Childhood Leukaemia
Authors: T. Hakulinen, L. Hovi, M. Karkinen-Jaaskelainen, K. Penttinen, L. Saxen
Journal: BMJ (1973)

This report based on the data available from the Finnish Cancer Registry and from virus isolations gives further support to the association (P=0.04) between maternal influenza of the 1957 "Asian" type and subsequent later leukaemia in the infants. No such association was found from other influenza epidemics.
Reactivity of isolated porcine coronary resistance arteries to cholinergic and adrenergic drugs and transmural pressure changes.
Authors: K Nakayama, G Osol, W Halpern
Journal: Circulation Research (1988)

The reactivity of porcine intramyocardial resistance arteries (223 +/- 7 micron i.d., n = 30) was investigated with a pressurized in vitro preparation. Diameter changes in response to acetylcholine and to adrenergic drugs and dynamic changes in transmural pressure changes were investigated. Acetylcholine produced concentration-dependent constrictions, causing maximal reductions of 71 +/- 3% in lumen diameter, with EC50 values averaging 1.9 X 10(-7) M (n = 7). These responses were inhibited by atropine (10(-7) M) and therefore were mediated by muscarinic receptors. In addition, acetylcholine did not elicit relaxation in nine out of 10 vessels precontracted with U46619 (10(-7) M). Norepinephrine and epinephrine never produced constrictions (n = 6) even in the presence of propranolol (10(-6) M). Both norepinephrine and isoproterenol caused dose-dependent relaxations in acetylcholine-precontracted vessels, with IC50 values of 8.2 X 10(-7) M (n = 5) and 6.6 X 10(-8) M (n = 6), respectively. These relaxations were suppressed by propranolol. Between transmural pressures of 10 and 90 mm Hg, there was no intrinsic myogenic tone (n = 7). In addition, the vessels responded only passively to sudden pressure changes of 40 mm Hg. In all vessels, the functional integrity of the endothelium was verified by relaxations to substance P (10(-8) M) and/or bradykinin (10(-8) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Frequency of pancreatitis in fulminant hepatic failure using isoenzyme markers.
Authors: R J Ede, K P Moore, W J Marshall, R Williams
Journal: Gut (1988)

Evidence of acute pancreatitis was sought in 35 patients with fulminant hepatic failure. Total amylase was raised in 22 patients and isoenzyme separation showed a distinct P3 isoenzyme (indicative of pancreatitis) in 14. In four patients with marked hyperamylasaemia (greater than 1000 U/l) the predominant isoenzyme was the salivary fraction. Pancreatic lipase was abnormally raised (greater than 200 U/l) in 34 patients but exceeded 1000 U/l in 12 of the 14 with a distinct P3 isoenzyme. Thus on the basis of a distinct P3 isoenzyme of amylase and an increased pancreatic lipase activity evidence of pancreatitis was found in 34% of patients in this series.
Intracellular Targets of Matrix Metalloproteinase-2 in Cardiac Disease: Rationale and Therapeutic Approaches
Authors: Richard Schulz
Journal: The Annual Review of Pharmacology and Toxicology (2006)

A new paradigm of matrix metalloproteinase-2 (MMP-2) action in the heart undergoing oxidative stress has emerged. Although best known for its role in the proteolysis of extracellular protein targets, MMP-2 is also localized to the sarcomere within the cardiomyocyte. Oxidative stress activates full-length MMP-2 without need for proteolytic processing and inactivates an endogenous inhibitor, tissue inhibitor of metalloproteinase-4. MMP-2 proteolyzes specific targets within the cell to cause acute, reversible contractile dysfunction. Inhibitors of MMPs are discussed and their possible use for the therapy of acute heart injury caused by oxidative stress is examined.
Sodium channels from human brain RNA expressed in Xenopus oocytes. Basic electrophysiologic characteristics and their modification by diphenylhydantoin.
Authors: G F Tomaselli, E Marban, G Yellen
Journal: Journal of Clinical Investigation (1989)

We describe the expression and characterization of sodium channels from human brain RNA in the Xenopus oocyte. The expressed channel, studied by whole-cell voltage clamp, reveals characteristic selectivity for sodium as the permeant ion, voltage-dependent gating, and block by nanomolar concentrations of tetrodotoxin. Such channels are not seen in control oocytes injected with solvent only. The anticonvulsant diphenylhydantoin (DPH) inhibits the expressed channel in a voltage- and use-dependent manner, much like the effect seen in primary mammalian neuronal preparations. The inhibition of the expressed human sodium channel by DPH can be described by models previously developed to explain block of Na channels by local anesthetics. The preferential block of Na channels during depolarization helps explain the selectivity of DPH for neurons involved in seizure activity.
Proteasome Inhibitor MG132 Induces Death Receptor 5 through CCAAT/Enhancer-Binding Protein Homologous Protein
Authors: Tatsushi Yoshida, Takumi Shiraishi, Susumu Nakata, Mano Horinaka, Miki Wakada, Yoichi Mizutani, Tsuneharu Miki, Toshiyuki Sakai
Journal: Cancer Research (2005)

Abstract Combined treatment with a proteasome inhibitor and tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is a promising strategy for cancer therapy. Proteasome inhibitors induce the expression of death receptor 5 (DR5), a receptor for TRAIL, and sensitize cancer cells to TRAIL-induced apoptosis; however, the molecular mechanism of DR5 up-regulation has not been elucidated. In this study, we report that CCAAT/enhancer-binding protein homologous protein (CHOP) is a regulator of DR5 induction by proteasome inhibitor MG132. MG132 induced DR5 expression at a protein and mRNA level in prostate cancer DU145 cells. Furthermore, MG132 increased DR5 promoter activity. Using a series of deletion mutant plasmids containing DR5 promoters of various sizes, we found that MG132 stimulated the promoter activity via the region of −289 to −253. This region contained a CHOP-binding site. Site-directed mutation of the site abrogated the promoter activity enhanced by MG132. An electrophoretic mobility shift assay showed that CHOP directly bound to the MG132-responsive site on the DR5 promoter. Expression of the CHOP protein was increased with MG132 along with DR5 up-regulation. Furthermore, CHOP small interfering RNA attenuated the DR5 up-regulation due to MG132. These results indicate that the proteasome inhibitor MG132 induces DR5 expression through CHOP up-regulation.
COMMON CELL SURFACE ANTIGEN ASSOCIATED WITH MAMMALIAN C-TYPE RNA VIRUSES
Authors: Takashi Yoshiki, Robert C. Mellors, William D. Hardy, Erwin Fleissner
Journal: The Journal of Experimental Medicine (1974)

The indirect membrane immunofluorescence test and the absorption analysis of rabbit anti-FeLV, rabbit anti-FeLVp 30, and rabbit anti-MuLVp 30 antisera yielded the following conclusions. An antigen shared by mammalian (murine and feline) C-type RNA leukemia and sarcoma viruses was detected on the surface of cells infected or transformed by C-type viruses. The antigen was characterized as membrane-bound gs antigen bearing two determinants, membrane-bound gs-1, intraspecies-specific antigenic determinant, and membrane-bound gs-3, interspecies-specific antigenic determinant. Membrane-bound gs antigen was located on the cell surface, frequently near the site of virus budding but not on the envelope of murine C-type RNA virus.
US new drug applications increasingly rely on trials conducted abroad
Authors: J. H. Tanne
Journal: BMJ (2010)

Applications to the US Food and Drug Administration for approval of new drugs and biologicals increasingly rely on foreign trials, says a new report.

The report, from the FDA’s parent organisation—the federal Health and Human Services Administration—says that in 2008, 80% of approved marketing applications contained data from foreign clinical trials and 78% of participants in clinical trials were foreign.⇓ Nine drugs and one biological were approved solely on the basis of clinical trials from outside the US.



The report says, “Western Europe accounted for the most clinical trial subjects and sites; however Central and South America had the highest average number of subjects per site…The percentage of foreign …
A Guide to Learning Fluid Therapy
Authors: M. David Orrahood
Journal: JAMA (1964)

The secret of learning therapy of fluid and electrolyte imbalance is to master the basic physiological principles. Such is the theme of this book, convincingly demonstrated by an author who has a gift of organizing a vast physiology literature and selecting the essentials, and also a gift of expressing these intricate relations in simple fashion.  The first four chapters, discussing body composition, present the Henderson-Hasselbalch equation and related mathematical concepts in a manner so skillful that the student achieves insight without expending a great deal of effort. Chapter 5 on Circulation is a broad and welcome review of cardiovascular physiology. In the chapter Acid-Base Equilibrium of Blood failure to furnish adequate definitions may cause confusion in parts of the text, but one would not expect entirely smooth sailing on this complicated subject. The remaining chapters, always returning to basic principles, offer unusually authoritative insight into the treatment of fluid imbalance.
959 HIGHLY PREVALENT ALT ABNORMALITIES IN MYCOPLASMA PNEUMONIAE INFECTION
Authors: S.H. Park, J.H. Kim, I.J. Lee, Y.J. Jang, T.H. Hahn, M.K. Jang, J.B. Kim, D.J. Kim, M.S. Lee, C.K. Park
Journal: Journal of Hepatology (2008)
Comparison of clinical outcome between patients continuing and discontinuing lamivudine therapy after biochemical breakthrough of YMDD mutants
Authors: Chien-Hung Chen, Chuan-Mo Lee, Sheng-Nan Lu, Jing-Houng Wang, Hung-Da Tung, Chao-Hung Hung, Wei-Jen Chen, Chi-Sin Changchien
Journal: Journal of Hepatology (2004)
Website of the week: Nosing around:
Authors: B. Twisselmann
Journal: BMJ (2002)

Smells, as Liam Farrell points out in his column (p 553), have the power to blank out other sensations in our lives completely. This seems to be true even while just reading about them. And that's not only bad smells. A survey of people's favourite smells on the internet (http://dspace.dial.pipex.com/town/avenue/as07/yourniffs.htm) provides comprehensive lists, grouped under atmospheric, body parts, chemicals, commercial perfumes and scents, essential oils, flowers, food and drink, fruit, materials, medicines, miscellaneous, household objects, pets, and trees. And while cat's urine is not among those, rain soaked dog seems to do for some people what freshly lit matches, chlorine bleach, or photocopier smells do for others. Reassuringly, fresh cut grass, freshly washed hair, and roses are also included in the list.

It's a shame the internet does not offer scratch and sniff technology (although the scratch and sniff page at www.bright.net/∼mamba/scratch.html may offer some surprises on that front), as some of the items listed seem on the slightly bizarre side.

A more scientific approach to the phenomenon of smells can be found at www.hhmi.org/senses/ (Seeing, hearing, and smelling the world, a report from the Howard Hughes Medical Institute). This describes the discovery of the odorant receptor proteins by two American scientists in 1991, explains how we remember or recognise odours, and how we sniff out sexual and social signals. For those who are particularly interested in the mysteries of odour in human sexuality, www.pheromones.com offers “an engrossing read on a whole new world under our noses.”

The web based smells database of the chemistry department at Berkeley university in California, United States (http://mc2.cchem.berkeley.edu/Smells/index.html), lists what it calls “interesting smells.” These include chemicals with disagreeable and agreeable sounding smells (hydrogen sulfide—smells of rotten eggs; beta-phenyl ethyl alcohol—smells like roses), complete with graphic representations and chemical attributes.