tbuckley/cabot-search huggingface dataset:
Atypical Protease-Activated Receptor Mediates Endothelium-Dependent Relaxation of Human Coronary Arteries
Authors: Justin R. Hamilton, Paul B. Nguyen, Thomas M. Cocks
Journal: Circulation Research (1998)

Abstract —Protease-activated receptors (PARs) are a family of G protein–coupled receptors activated by a tethered ligand sequence within the amino terminal that are revealed by site-specific proteolysis. The thrombin-sensitive PAR-1 and trypsin-activated PAR-2 mediate endothelium-dependent vascular relaxation in a number of species. Because both thrombin and trypsin-like enzymes have been implicated in coronary artery disease, the purpose of this study was to investigate whether similar receptors are present in human coronary arteries. Thrombin (0.001 to 0.1 U/mL) and trypsin (0.001 to 1 U/mL) caused concentration- and endothelium-dependent relaxations of human coronary artery ring segments suspended in organ chambers for isometric tension recording and contracted with the thromboxane A 2 mimetic U46619. These relaxations were dependent on the catalytic activity of each enzyme and were inhibited by the NO synthase inhibitor N G -nitro- l -arginine (100 μmol/L) and the NO scavenger oxyhemoglobin (20 μmol/L). The synthetic PAR-1 tethered ligand sequence SFLLRN-NH 2 (0.01 to 10 μmol/L) also caused endothelium-dependent relaxation of U46619-contracted human coronary arteries; however, the equivalent PAR-2 ligand SLIGKV-NH 2 caused almost no relaxation. In addition, desensitization to either thrombin or trypsin resulted in cross-desensitization to the other enzyme but had only a minimal affect on the response to SFLLRN-NH 2 . Therefore, we conclude that human coronary artery endothelial cells possess a PAR-1–like receptor that is potently activated by thrombin, trypsin, and SFLLRN-NH 2 to cause NO-mediated vascular relaxation. Once cleaved, this receptor is recycled in a truncated form, able to respond to exogenous application of only its tethered ligand sequence, suggesting the presence of another endogenous activator possibly acting independently of receptor cleavage.
The Work of a Family Doctor
Authors: Lawrence L. Hirsch
Journal: JAMA (1969)

What could have been a monumental bore is instead a pleasant experience. Opening with a demand that the family doctor have a "marked degree of humaneness" as well as a "profound... medical knowledge," the book demonstrates that the author has both. After clearly describing the design and method of his study, McGregor presents his material in ten graphs and 151 tables. All patients seen from July 5, 1948 (the first day of the British National Health service), to January 5, 1960, are tabulated. The difficulty of cataloging 11 1/2 years' experience in a busy general practice is resolved by using the systemic as well as symptomatic approach. McGregor's use of brief, pointed examples or succinct comments gives perspective and readability to the occasionally redundant material. The author closes his research report with a description of the split of the British medical community and the resultant problems of physician and hospital
Asterixis
Authors: Harold O Conn
Journal: New England Journal of Medicine (1958)

ASTERIXIS, which is commonly known as the "liver flap," was first demonstrated by Adams and Foley1 in 1949 as a neurologic abnormality characteristic of severe liver disease. In 1953, these authors coined the term asterixis2 (from the Greek sterigma, to support), which literally means the inability to maintain a fixed posture. One can elicit this sign by having the patient extend his arms and forearms and dorsiflex his hands for several minutes. Within a minute, a series of sudden, rapid, flexion-extension movements appear at the wrist. These arrhythmic, to-and-fro movements, which last only a fraction of a second, frequently occur . . .
MEK kinase 1 activity is required for definitive erythropoiesis in the mouse fetal liver
Authors: Barbara Bonnesen, Cathrine Orskov, Susanne Rasmussen, Peter Johannes Holst, Jan Pravsgaard Christensen, Karsten Wessel Eriksen, Klaus Qvortrup, Niels Odum, Tord Labuda
Journal: Blood (2005)
Advantages and limitations of Internet-based interventions for common mental disorders
Authors: Gerhard Andersson, Nickolai Titov
Journal: World Psychiatry (2014)

Several Internet interventions have been developed and tested for common mental disorders, and the evidence to date shows that these treatments often result in similar outcomes as in face-to-face psychotherapy and that they are cost-effective. In this paper, we first review the pros and cons of how participants in Internet treatment trials have been recruited. We then comment on the assessment procedures often involved in Internet interventions and conclude that, while online questionnaires yield robust results, diagnoses cannot be determined without any contact with the patient. We then review the role of the therapist and conclude that, although treatments including guidance seem to lead to better outcomes than unguided treatments, this guidance can be mainly practical and supportive rather than explicitly therapeutic in orientation. Then we briefly describe the advantages and disadvantages of treatments for mood and anxiety disorders and comment on ways to handle comorbidity often associated with these disorders. Finally we discuss challenges when disseminating Internet interventions. In conclusion, there is now a large body of evidence suggesting that Internet interventions work. Several research questions remain open, including how Internet interventions can be blended with traditional forms of care.
Systemic Arterial Blood Supply to a Normal Lung
Authors: Daniel C. Campbell
Journal: JAMA (1962)

THE LITERATURE contains numerous reports of anomalous pulmonary arteries from the systemic circulation that supplies abnormal pulmonary tissue. For a long time it has been recognized that systemic arteries may supply normal lung. However, the majority of the more recent reports describe only systemic arteries which supply sequestered lobes or segments or those in which frank pulmonary suppurative disease exists. When the pulmonary parenchyma which the systemic artery supplies has been the seat of suppuration, it is difficult to determine whether the systemic artery constitutes a true congenital anomaly or a hypertrophy of the bronchial arterial supply caused by the inflammatory reaction. Troublesome bleeding, and even deaths, have been associated with the division of some of these arteries. In 1947, Pryce, Sellors, and Blair stated that anomalous arteries were reported more often than sequestrations. They classified these arteries into 3 types: Type 1, an abnormal artery (systemic) to normal lung;
High Levels of Persistent Expression of α1-Antitrypsin Mediated by the Nonhuman Primate Serotype rh.10 Adeno-associated Virus Despite Preexisting Immunity to Common Human Adeno-associated Viruses
Authors: Bishnu P. De, Adriana Heguy, Neil R. Hackett, Barbara Ferris, Philip L. Leopold, John Lee, Lorraine Pierre, Guangping Gao, James M. Wilson, Ronald G. Crystal
Journal: Molecular Therapy (2005)

Alpha1-antitrypsin (alpha1AT) deficiency is a genetic disorder causing emphysema if serum alpha1AT levels are <570 microg/ml. We have shown that intrapleural administration of an AAV5alpha1AT vector yielded persistent therapeutic alpha1AT serum levels. Since anti-AAV2 and -AAV5 antibodies prevalent in humans may limit the use of these common serotypes in gene therapy, we screened 25 AAV vectors derived from humans and nonhuman primates for alpha1AT expression following intrapleural administration to mice. The rhesus AAVrh.10 serotype yielded the highest levels and was chosen for further study. Following intrapleural administration, 77% of total body transgene expression was in the chest wall, diaphragm, lung, and heart. Intrapleural administration of AAVrh.10alpha1AT provided long-term, therapeutic alpha1AT expression in mice, although higher doses were required to achieve therapeutic levels in female mice than in male mice. Intrapleural administration of AAVrh.10alpha1AT produced the same levels in AAV2/AAV5-preimmune and naive mice. In mice administered with AAV5alpha1AT and subsequently "boosted" with the AAVrh.10alpha1AT vector, serum levels were increased by 300%. These data indicate that AAVrh.10 is the most effective known AAV vector for intrapleural gene delivery and has the advantage of circumventing human immunity to AAV.
Row over planned closure of leprosarium in the Philippines
Authors: A. Easton
Journal: BMJ (1997)

Health workers in the Philippines have accused the government of forcing patients with leprosy out on to the streets as part of their plan to convert a leprosarium into a general hospital.

The Council for Health Development said that the patients at the 130 hectare Tala leprosarium in Caloocan City, 30 miles north of Manila, are being offered £250 ($420) each to discharge themselves from the centre to make …
Inhibin A Is Downregulated during Chemotherapy in Patients with Early Breast Cancer.
Authors: B. Rack, N. Burkhardt, J. Jueckstock, C. Kuhn, S. Noeding, A. Hoenig, M. Friedrich, C. Schindlbeck, H. Sommer, K. Friese, W. Janni, [. Mylonas
Journal: Cancer Research (2009)

Abstract Introduction: Inhibins are dimeric glycoproteins, composed of an alpha-subunit (INH-a) and one of two possible beta-subunits (ßA or ßB), with substantial roles in human reproduction and in endocrine-responsive tumours. In breast cancer tissue, the growth factor Inhibin A is involved in cell differentiation and proliferation, thus suggesting a possible role as tumor marker. Aims of this study were to determine the serological measurement of Inhibin A (a- bA) in breast cancer patients during chemotherapy.Material and Methods: A series of 28 high risk N0 and N+ breast cancer patients who underwent standardized chemotherapy (3 x FEC and 3 x Docetaxel) followed by two years of zoledronate in the German SUCCESS trial were prospectively evaluated before chemotherapeutic treatment as well as after chemotherapy and two years after chemotherapy for the serological expression of Inhibin A. For serological analysis the ultrasensitive Inhibin A ELISA (DSL – U.S.A.) was used according to manufactures instruction. For statistical analysis the Wilcoxon rang sum test was used for paired samples. Statistical significance was assumed at p&amp;lt; 0.05.Results: The concentration of Inhibin A showed a significant decrease between data obtained before chemotherapy and after chemotherapy (p&amp;lt;0.005) and two-year follow up (p&amp;lt;0.001). Interestingly, there were seen no differences between the time point four weeks after chemoherapy and at two years (p=0.744).Discussion: Therefore, chemotherapy decreases significantly the Inhibin A concentration during chemotherapy. This might reflect a suppression of ovarian function and might be a marker for chemotherapy-induced amenorrhoea. Moreover, it has been suggested that Inhibin A might be a tumour marker for breast cancer, and therefore a sudden increase of its concentration might be indicative of breast cancer recurrence. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3028.
Prosthetic valve endocarditis.
Authors: T S Ivert, W E Dismukes, C G Cobbs, E H Blackstone, J W Kirklin, L A Bergdahl
Journal: Circulation (1984)

Fifty-three (3.6%; actuarially 4.1% at 48 months) of 1465 consecutive in-hospital survivors of valve replacement from 1975 to July 1979 (aortic, mitral, or aortic and mitral, only one untraced) developed prosthetic valve endocarditis (PVE). Incremental risk factors for developing PVE were native valve endocarditis (p less than .0001), black race (p = .0001), mechanical prosthesis (vs bioprosthesis) (p = .005), male sex (p = .04), and longer cardiopulmonary bypass time (p = .09). In general, the hazard function for developing PVE was greatest at 3 weeks after valve replacement. Patients with native valve endocarditis had a tendency to develop PVE early after valve replacement, as did patients in whom mechanical prostheses were used. PVE associated with Staphylococcus epidermidis tended to appear within 6 months of valve replacement, whereas streptococcal PVE tended to appear later after valve replacement. PVE took an atypical form in some patients, but patients with possible PVE (n = 6) had the same findings as those with certain PVE (n = 47). In 11 patients bacteriologic confirmation of PVE was not obtained. The typical prosthetic and periprosthetic characteristics of PVE were present in 30 of the 40 cases in which observations were possible. PVE is a serious condition; 34 (64%) of our 53 patients died. Most deaths occurred within 3 months of the first evidence of PVE. Recovery of some patients is possible with appropriate medical and surgical treatment, but more intense preventive measures are indicated.
Three-dimensional motion reconstruction and analysis of the right ventricle using tagged MRI
Authors: I. Haber, Dimitris N. Metaxas, Leon Axel
Journal: Medical Image Analysis (2000)

Right ventricular (RV) dysfunction can serve as an indicator of heart and lung disease and can adversely affect the left ventricle. However, normal RV function must be characterized before abnormal states can be detected. We describe a method for reconstructing the 3D motion of the RV by fitting a deformable model to tag and contour data extracted from multiview tagged magnetic resonance images. The deformable model is a biventricular finite element mesh built directly from segmented contours. Our approach accommodates the geometrically complex RV by using the entire lengths of the tags, localized degrees of freedom, and finite elements for geometric modeling. Also, we outline methods for converting the 3D motion reconstruction results into potentially useful motion variables, such as strains and displacements. The technique was applied to synthetic data, two normal hearts, and two hearts with right ventricular hypertrophy (RVH). Noticeable differences were found between the motion variables calculated for normal volunteers and RVH patients.
Deep sedation for endoscopic retrograde cholangiopancreatography: intravenous propofol alone versus intravenous propofol with oral midazolam premedication
Authors: G. Paspatis, M. Manolaraki, E. Vardas, A. Theodoropoulou, G. Chlouverakis
Journal: Endoscopy (2007)

See also: Commentaire de travail de G. A. Paspatis et al., pp. 308Endoscopy 2008; 40(04): 452-453DOI: 10.1055/s-0032-1306827
The Use of Serologic Tests for Lyme Disease in a Prepaid Health Plan in California
Authors: Catherine Ley
Journal: JAMA (1994)

To determine the reason(s) why serologic tests for Lyme disease are performed, who initiates the test requests, and how the test results are used in a clinical setting.Retrospective cohort.Prepaid health plan in northern California.Consecutive sample of 117 patients for whom at least one serologic test for Lyme disease was performed during a 3-month period.Reason for ordering and result of the serologic test, differential diagnoses, and treatment.One of 117 patients had antibodies to Borrelia burgdorferi. Fifty-six percent of test requests were initiated by the physician and 35% by the patient. Of 66 tests ordered by the physician, 20% were performed because of suspected early Lyme disease, 6% as follow-up of a tick bite, 2% to confirm a prior history of Lyme disease, 14% as a workup for arthritis, and 60% as one of a battery of laboratory tests for vague symptoms. Of 41 tests initiated by the patient, 51% were performed because of a history of a tick bite. The reasons for ordering 10 tests were undetermined.Only 19% of all serologic tests for Lyme disease were performed because the physician suspected Lyme disease in the patient. Particularly in light of the low probability of contracting Lyme disease in California, it appears that this serologic test is being overused. Indiscriminate testing increases health care costs and does not appear to affect treatment decisions. Education is needed regarding the limitations of this serologic test.
Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis
Authors: Ikuyo Kou, Yohei Takahashi, Todd A Johnson, Atsushi Takahashi, Long Guo, Jin Dai, Xusheng Qiu, Swarkar Sharma, Aki Takimoto, Yoji Ogura, Hua Jiang, Huang Yan, Katsuki Kono, Noriaki Kawakami, Koki Uno, Manabu Ito, Shohei Minami, Haruhisa Yanagida, Hiroshi Taneichi, Naoya Hosono, Taichi Tsuji, Teppei Suzuki, Hideki Sudo, Toshiaki Kotani, Ikuho Yonezawa, Douglas Londono, Derek Gordon, John A Herring, Kota Watanabe, Kazuhiro Chiba, Naoyuki Kamatani, Qing Jiang, Yuji Hiraki, Michiaki Kubo, Yoshiaki Toyama, Tatsuhiko Tsunoda, Carol A Wise, Yong Qiu, Chisa Shukunami, Morio Matsumoto, Shiro Ikegawa
Journal: Nature Genetics (2013)
Cholera: The American Scientific Experience, 1947-1980.
Authors: W. E. van Heyningen, John R. Seal
Journal: Annals of Internal Medicine (1983)

Cholera: the American Scientific experience 1947-1980 , Cholera: the American Scientific experience 1947-1980 , کتابخانه مرکزی دانشگاه علوم پزشکی تهران
COMPARISON OF TRANSRADIAL AND FEMORAL APPROACHES FOR PERCUTANEOUS CORONARY INTERVENTIONS: A HIERARCHICAL BAYESIAN META-ANALYSIS
Authors: Olivier F. Bertrand, Patrick Belisle, Dominique Joyal, Olivier Costerousse, Sunil V. Rao, Sanjit Jolly, David Meerkin, Lawrence Joseph
Journal: Journal of the American College of Cardiology (2011)
C3-03: Randomized, phase III Study of mitomycin/vindesine/cisplatin (MVP) versus weekly irinotecan/carboplatin (IC) or weekly paclitaxel/carboplatin (PC) with concurrent thoracic radiotherapy (TRT) for unresectable stage III non-small-cell lung cancer (NSCLC): WJTOG0105
Authors: Kimihide Yoshida, Hisao Uejima, Miyako Satouchi, Shinzoh Kudoh, Kazuhiko Nakagawa, Toyoaki Hida, Masaaki Kawahara, Takamune Sugiura, Kenji Tamura, Masahiro Fukuoka
Journal: Journal of Thoracic Oncology (2007)
Environmental Exposure, Obesity, and Parkinson’s Disease: Lessons from Fat and Old Worms
Authors: Layla Aitlhadj, Daiana Silva Ávila, Alexandre Benedetto, Michael Aschner, Stephen Richard Stürzenbaum
Journal: Environmental Health Perspectives (2010)

A common link has been exposed, namely, that metal exposure plays a role in obesity and in Parkinson's disease (PD). This link may help to elucidate mechanisms of neurotoxicity.We reviewed the utility of the nematode, Caenorhabditis elegans, as a model organism to study neurodegeneration in obesity and Parkinson's disease (PD), with an emphasis on the neurotransmitter, dopamine (DA).A PubMed literature search was performed using the terms "obesity" and any of the following: "C. elegans," "central nervous system," "neurodegeneration," "heavy metals," "dopamine" or "Parkinson's disease." We reviewed the identified studies, including others cited therein, to summarize the current evidence of neurodegeneration in obesity and PD, with an emphasis on studies carried out in C. elegans and environmental toxins in the etiology of both diseases.Heavy metals and DA have both been linked to diet-induced obesity, which has led to the notion that the mechanism of environmentally induced neurodegeneration in PD may also apply to obesity. C. elegans has been instrumental in expanding our mechanism-based knowledge of PD, and this species is emerging as a good model of obesity. With well-established toxicity and neurogenetic assays, it is now feasible to explore the putative link between metal- and chemical-induced neurodegeneration.One side effect of an aging population is an increase in the prevalence of obesity, metabolic disorders, and neurodegenerative orders, diseases that are likely to co-occur. Environmental toxins, especially heavy metals, may prove to be a previously neglected part of the puzzle.
Healthcare leaders call for end to criticism of NHS in 2014
Authors: Z. Kmietowicz
Journal: BMJ (2014)

Relapse to drug use can be initiated by drug-associated cues. The intensity of cue-induced drug seeking in rodent models correlates with the induction of transient synaptic potentiation (t-SP) at glutamatergic synapses in the nucleus accumbens core (NAcore). Matrix metalloproteinases (MMPs) are inducible endopeptidases that degrade extracellular matrix (ECM) proteins, and reveal RGD domains that bind and signal through integrins. Integrins are heterodimeric receptors composed of αβ subunits, and a primary signaling kinase is focal adhesion kinase (FAK). We previously showed that MMP activation is necessary for and potentiates cued reinstatement of cocaine seeking, and MMP-induced catalysis stimulates β3-integrins to induce t-SP. Here we determined if β3-integrin signaling through FAK and cofilin (actin depolymerization factor) is necessary to promote synaptic growth during t-SP. Using a small molecule inhibitor to prevent FAK activation, we blocked cued-induced cocaine reinstatement and increased spine head diameter (d<sub>h</sub>). Immunohistochemistry on NAcore labeled spines with ChR2-EYFP virus, showed increased immunoreactivity of p-FAK and p-cofilin in dendrites of reinstated animals compared to extinguished and yoked saline, and the phosphorylation of FAK and cofilin depended on β3-integrin signaling. Next, male and female transgenic rats were used to selectively label D1 or D2 neurons with ChR2-mCherry. We found that p-FAK was increased during drug seeking in both D1 and D2-MSNs, but increased p-cofilin was observed only in D1-MSNs. These data indicate that β3-integrin, FAK and cofilin constitute a signaling pathway downstream of MMP activation that is involved in promoting the transient synaptic enlargement in D1-MSNs induced during reinstated cocaine by drug-paired cues. <b>SIGNIFICANCE STATEMENT</b> Drug-associated cues precipitate relapse, which is correlated with transient synaptic enlargement in the accumbens core. We showed that cocaine cue-induced synaptic enlargement depends on matrix metalloprotease signaling in the extracellular matrix through β3-integrin to activate focal adhesion kinase and phosphorylate the actin binding protein cofilin. The NAcore contains two predominate neuronal subtypes selectively expressing either D1- or D2-dopamine receptors. We used transgenic rats to study each cell type and found that cue-induced signaling through cofilin phosphorylation occurred only in D1-expressing neurons. Thus, cocaine-paired cues initiate cocaine reinstatement and synaptic enlargement through a signaling cascade selectively in D1-expressing neurons requiring extracellular matrix stimulation of β3-integrin-mediated phosphorylation of focal adhesion kinase and cofilin.
A hundred years ago
Authors: P J Toghill
Journal: British Journal of Sports Medicine (1997)

Leadersabuse would result in a syndrome similar to acromegaly with attendant risks of hypertension, cardiomyopathy, malignancy, myopathy, peripheral neuropathy, and glucose intolerance.Thus while GH at physiological levels has major beneficial effects, its abuse leaves the athlete at high risk, and it behoves the medical and scientific communities to curtail its use as a doping agent.
Amidopyrine and Agranulocytosis
Authors: R. G. Simpson
Journal: BMJ (1963)

Antihistamines and the Ovum SIR,-At the Seventh Conference of the Federation on Planned Parenthood held recently in Singapore Profes- sor M. C. Shelesnyak showed that for implantation of the fertilized ovum to be successful not only must oestrogens and progesterones be necessary but a third substance, histamine, is required, and successful " nest- ing" depends on the interplay of these three.Presumably the temporary stoppage of the production of any of these three substances would halt the process of implantation and consequently impede pregnancy.It would appear, therefore, that antihistamines might prevent satisfactory implantation of the fertilized ovum and pregnancy.If this is the case, surely considerable caution should be exercised in the giving of antihistamine drugs to those about to start a family ?-Iam, etc.,