tbuckley/cabot-search huggingface dataset:
Inorganic Arsenite Potentiates Vasoconstriction through Calcium Sensitization in Vascular Smooth Muscle
Authors: Moo-Yeol Lee, Young-Ho Lee, Kyung-Min Lim, Seung-Min Chung, Ok-Nam Bae, Heon Kim, Choong-Ryeol Lee, Jung-Duck Park, Jin-Ho Chung
Journal: Environmental Health Perspectives (2005)

Chronic exposure to arsenic is well known as the cause of cardiovascular diseases such as hypertension. To investigate the effect of arsenic on blood vessels, we examined whether arsenic affected the contraction of aortic rings in an isolated organ bath system. Treatment with arsenite, a trivalent inorganic species, increased vasoconstriction induced by phenylephrine or serotonin in a concentration-dependent manner. Among the arsenic species tested—arsenite, pentavalent inorganic species (arsenate), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV)—arsenite was the most potent. Similar effects were also observed in aortic rings without endothelium, suggesting that vascular smooth muscle plays a key role in enhancing vasoconstriction induced by arsenite. This hypercontraction by arsenite was well correlated with the extent of myosin light chain (MLC) phosphorylation stimulated by phenylephrine. Direct Ca2+ measurement using fura-2 dye in aortic strips revealed that arsenite enhanced vasoconstriction induced by high K+ without concomitant increase in intracellular Ca2+ elevation, suggesting that, rather than direct Ca2+ elevation, Ca2+ sensitization may be a major contributor to the enhanced vasoconstriction by arsenite. Consistent with these in vitro results, 2-hr pretreatment of 1.0 mg/kg intravenous arsenite augmented phenylephrine-induced blood pressure increase in conscious rats. All these results suggest that arsenite increases agonist-induced vasoconstriction mediated by MLC phosphorylation in smooth muscles and that calcium sensitization is one of the key mechanisms for the hypercontraction induced by arsenite in blood vessels.
Retracing the Oregon trail: the experience of rationing and the Oregon health plan
Authors: C. Ham
Journal: BMJ (1998)

A decade ago the state of Oregon attracted worldwide interest when it began an ambitious attempt to set priorities for health care on a systematic basis. Stimulated by the death of a 7 year old boy who had been waiting for a bone marrow transplant operation, and led by John Kitzhaber, a doctor turned politician, Oregon passed legislation in 1989 designed to provide access to health insurance for all residents. A key part of the strategy was to increase eligibility for Medicaid, a publicly funded programme of health care for people with low incomes, by including in the programme all citizens with an income at or below 100% of the federally defined poverty level. To keep the costs of this policy within affordable limits, the legislature determined that the services provided should constitute a basic healthcare package, and it sought to ensure that Medicaid recipients were, whenever possible, enrolled in managed care plans. These plans, often known as health maintenance organisations, have developed rapidly as an alternative to fee for service medicine, and provide services to those enrolled on a prepaid basis. By managing the use of services by both patients and doctors, health maintenance organisations seek to reduce the overall cost of providing care while maintaining high standards of provision.

#### Summary points

The basic healthcare package available to those eligible for Medicaid coverage under the Oregon health plan has been expanded. Enrolment in Medicaid has increased by over 100 000 since 1994 but eligibility criteria have been tightened in response to rising costs

The proportion of the population that remains uninsured has fallen from 18% in 1993 to 11% in 1996 as a result of implementation of the plan and economic growth

Providers of safety net services may not be able to continue to provide such services under the plan's payment …
Common variable immunodeficiency: two mutations are better than one
Authors: Antonio La Cava
Journal: Journal of Clinical Investigation (2013)

B cells from common variable immunodeficiency (CVID) patients who have one mutant copy of the gene encoding the transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) often display dysfunctional antibody production. Interestingly, some individuals with mutations in both TACI alleles do not present with CVID, suggesting that TACI mutations influence CVID pathogenesis via dominant interference or haploinsufficiency. In this issue of the JCI, Romberg and colleagues report how TACI mutations impact B cell activation, removal of autoreactive B cells, and the development of autoimmune disease in CVID.
How a Natural Molecule May Protect Against Autoimmune Diseases
Authors: Tracy Hampton
Journal: JAMA (2014)

Nicotinamide adenine dinucleotide (NAD+)—the coenzyme form of the vitamin niacin and a natural molecule found in all living cells—may help protect against autoimmune diseases by regulating how CD4+ T cells differentiate, researchers report (Tullius SG et al. Nat Commun. 2014;5:5101).
Diagnostic Accuracy of an “Amended” Insulin–Glucose Ratio for the Biochemical Diagnosis of Insulinomas
Authors: Michael A. Nauck, Juris J. Meier
Journal: Annals of Internal Medicine (2012)

Background: Recent biochemical diagnostic guidelines for insulinomas require demonstration of hypoglycemia with inappropriately elevated (nonsuppressed) insulin, C-peptide, or proinsulin, but these criteria may overlap with those in patients without insulinomas. Use of an "amended" insulin–glucose ratio that accounts for the normal variation in insulin secretion according to prevailing glycemia may improve diagnostic accuracy. Objective: To compare the diagnostic accuracy of current diagnostic guideline criteria with the amended insulin–glucose ratio in patients with a suspected insulinoma. Design: Retrospective cohort study. Setting: 2 specialized university departments in Germany. Patients: 114 patients with suspected hypoglycemia over 10 years having diagnostic prolonged fasts. Measurements: Glucose, insulin, C-peptide, and the amended insulin–glucose ratio were measured during and at discontinuation of prolonged fasts. Results: Of 114 patients who were evaluated, 49 had surgical resection of histologically confirmed insulinomas. Insulinoma was excluded in 65 patients; follow-up for a mean of 10 years (range, 0 to 16 years) showed no progressively severe hypoglycemic events or diagnoses of insulinoma. Patients with insulinoma had lower glucose levels and higher insulin and C-peptide levels overall than did control patients at the end of prolonged fasts, but there was considerable overlap. The amended insulin–glucose ratio correctly identified 48 of 49 patients with insulinoma and excluded the diagnosis in 64 of 65 control patients, resulting in positive and negative predictive values of 0.98 (95% CI, 0.89 to 1.00) and 0.99 (CI, 0.92 to 1.00), respectively, compared with 0.75 (CI, 0.63 to 0.85) and 0.98 (CI, 0.89 to 1.00), respectively, for glucose, insulin, and C-peptide concentration criteria. Limitation: The study had a retrospective design, no proinsulin concentrations were available, and a nonspecific insulin immunoassay (crossreactive with proinsulin) was used. Conclusion: The amended insulin–glucose ratio showed improved diagnostic accuracy over established criteria that use glucose, insulin, and C-peptide concentrations. Primary Funding Source: None.
STUDIES ON THE SUPRARENAL CORTEX
Authors: George A. Harrop, George W. Thorn
Journal: The Journal of Experimental Medicine (1937)

The effect of the administration of suprarenal cortical hormone upon the excretion of sodium and potassium has been studied on normal dogs. It is shown to be qualitatively similar to the effect of this hormone upon suprarenalectomized animals and upon patients with Addison's disease. The phenomenon is proposed as the basis for a suitable method for comparative assay of suprarenal cortical extracts. The method is simple, time saving, and uses a minimum of extract.
Increasing the uptake of cervical smear testing among Asian women.
Authors: T Hoare, C Johnson
Journal: BMJ (1991)

mortalitv, is deliberately!misleading: the excess deaths were due to distant metastases.T! hese deaths were inevitable even before the patients entered the flawed trial.We know that this was the basis for the rejection of the study as totally inappropriate by the Radiation Therapy Oncology Group's fast neutron group in the US.So why waste time, precious resources, and the trust of patients?Yet Dr Errington and colleagues have persevered and delivered another antineutron headline.Such a headline might have been critical to the project to get a cyclotron where it would be used effectively for the benefit of patients.But this had already been torpedoed-after a brilliant, well orchestrated campaign-bv the withdrawal of what has been represented as the infamous Thatcher £6 million repayable loan-which was not a grant for cancer research, as is so often misreported, but a repayable loan for treatment.Happily, one important message that can be gleaned from this study is the absence of excess normal tissue morbidity in the pelvis of patients treated with 19 2 Gy of high energy neutrons in 12 fractions over 28 days.Further studies-sadly, probably elsewhere-will identify the true role for neutrons in treating advanced cancer.
New Generation of Plasmid Backbones Devoid of Antibiotic Resistance Marker for Gene Therapy Trials
Authors: Gaëlle Vandermeulen, Corinne Marie, Daniel Scherman, Véronique Préat
Journal: Molecular Therapy (2011)

Since it has been established that the injection of plasmid DNA can lead to an efficient expression of a specific protein in vivo, nonviral gene therapy approaches have been considerably improved, allowing clinical trials. However, the use of antibiotic resistance genes as selection markers for plasmid production raises safety concerns which are often pointed out by the regulatory authorities. Indeed, a horizontal gene transfer to patient's bacteria cannot be excluded, and residual antibiotic in the final product could provoke allergic reactions in sensitive individuals. A new generation of plasmid backbones devoid of antibiotic resistance marker has emerged to increase the safety profile of nonviral gene therapy trials. This article reviews the existing strategies for plasmid maintenance and, in particular, those that do not require the use of antibiotic resistance genes. They are based either on the complementation of auxotrophic strain, toxin–antitoxin systems, operator–repressor titration, RNA markers, or on the overexpression of a growth essential gene. Minicircles that allow removing of the antibiotic resistance gene from the initial vector will also be discussed. Furthermore, reported use of antibiotic-free plasmids in preclinical or clinical studies will be listed to provide a comprehensive view of these innovative technologies. Since it has been established that the injection of plasmid DNA can lead to an efficient expression of a specific protein in vivo, nonviral gene therapy approaches have been considerably improved, allowing clinical trials. However, the use of antibiotic resistance genes as selection markers for plasmid production raises safety concerns which are often pointed out by the regulatory authorities. Indeed, a horizontal gene transfer to patient's bacteria cannot be excluded, and residual antibiotic in the final product could provoke allergic reactions in sensitive individuals. A new generation of plasmid backbones devoid of antibiotic resistance marker has emerged to increase the safety profile of nonviral gene therapy trials. This article reviews the existing strategies for plasmid maintenance and, in particular, those that do not require the use of antibiotic resistance genes. They are based either on the complementation of auxotrophic strain, toxin–antitoxin systems, operator–repressor titration, RNA markers, or on the overexpression of a growth essential gene. Minicircles that allow removing of the antibiotic resistance gene from the initial vector will also be discussed. Furthermore, reported use of antibiotic-free plasmids in preclinical or clinical studies will be listed to provide a comprehensive view of these innovative technologies.
Assessing Prior History of Sexually Transmitted Disease
Authors: Jay M. Fleisher
Journal: JAMA (1991)

<h3>To the Editor.</h3> —Current estimates indicate that approximately 33% of women with the acquired immunodeficiency syndrome contract the disease heterosexually.<sup>1</sup>Women with a history of sexually transmitted diseases (STDs) are generally assumed to be at an increased risk for infection with the human immunodeficiency virus. One strategy for preventing heterosexually acquired human immunodeficiency virus infection among women is to identify those with a current or past history of an STD and to provide safe-sex counseling. Identifying women with a history of an STD is generally dependent on self-reporting. This approach is in turn dependent on women knowing about the many different diseases that fall under the rubric of "STDs." To examine women's knowledge of STDs, we analyzed data from a large ongoing prospective study of risk-taking attitudes and sexual behaviors of women at high risk for STDs. Information on a history of STDs was acquired from a cohort of
Parasympathetic Neural Activity Accounts for the Lowering of Exercise Heart Rate at High Altitude
Authors: Robert Boushel, Jose-Antonio L. Calbet, Goran Rådegran, Hans Sondergaard, Peter D. Wagner, Bengt Saltin
Journal: Circulation (2001)

Background In chronic hypoxia, both heart rate (HR) and cardiac output (Q) are reduced during exercise. The role of parasympathetic neural activity in lowering HR is unresolved, and its influence on Q and oxygen transport at high altitude has never been studied. Methods and Results HR, Q, oxygen uptake, mean arterial pressure, and leg blood flow were determined at rest and during cycle exercise with and without vagal blockade with glycopyrrolate in 7 healthy lowlanders after 9 weeks’ residence at ≥5260 m (ALT). At ALT, glycopyrrolate increased resting HR by 80 bpm (73±4 to 153±4 bpm) compared with 53 bpm (61±3 to 114±6 bpm) at sea level (SL). During exercise at ALT, glycopyrrolate increased HR by ≈40 bpm both at submaximal (127±4 to 170±3 bpm; 118 W) and maximal (141±6 to 180±2 bpm) exercise, whereas at SL, the increase was only by 16 bpm (137±6 to 153±4 bpm) at 118 W, with no effect at maximal exercise (181±2 bpm). Despite restoration of maximal HR to SL values, glycopyrrolate had no influence on Q, which was reduced at ALT. Breathing F io 2 =0.55 at peak exercise restored Q and power output to SL values. Conclusions Enhanced parasympathetic neural activity accounts for the lowering of HR during exercise at ALT without influencing Q. The abrupt restoration of peak exercise Q in chronic hypoxia to maximal SL values when arterial P o 2 and S o 2 are similarly increased suggests hypoxia-mediated attenuation of Q.
T Cell–Based Assay of Pericardial Fluid Mononuclear Cells for the Diagnosis of Tuberculous Pericardial Effusion
Authors: Sang Yong Om, Sung-Han Kim, Suk-Won Choi, Hyung Oh Choi, Yong-Giun Kim, Jong-Min Song, Sung-Ho Jung, Dae-Hee Kim, Duk-Hyun Kang, Jae-Kwan Song, Tae Sun Shim
Journal: Journal of the American College of Cardiology (2014)
Lactobacilli to Prevent Traveler's Diarrhea?
Authors: Peter H. Katelaris, Imroz Salam, Michael J.G. Farthing
Journal: New England Journal of Medicine (1995)

To the Editor: Acute diarrhea is the most common illness in travelers to high-risk areas, with up to half of those engaged in short-term travel affected.1 Although most episodes are mild and self-l...
Trypsin-induced, Neurokinin-mediated Contraction of Guinea Pig Bronchus
Authors: MICHAEL J. CARR, NORMAN M. SCHECHTER, BRADLEY J. UNDEM
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Proteases may act as cell signaling molecules via protease-activated receptors (PARs). PAR1, PAR3, and PAR4, but not PAR2, are activated by thrombin, whereas trypsin can activate PAR2 and PAR4. In this study, trypsin (3–100 nM) evoked concentration-dependent contractions of guinea pig isolated bronchus, however, thrombin (3–300 nM) was a weak spasmogen. Neither the PAR2-activating peptide SLIGRL (100 μ M) nor mast cell tryptase (100 nM), a trypsin-like protease known to activate PAR2, evoked contraction. A role for neurokinins in trypsin-induced contraction is suggested by our observation that contractions to trypsin were markedly attenuated in the presence of neurokinin receptor antagonists. Depletion of neurokinins in sensory nerves with capsaicin also markedly reduced the ability of trypsin to evoke contraction. In electrophysiological studies, trypsin did not evoke action potentials in C-fiber afferents whose receptive fields were located in the trachea or main bronchi. The results from this study support the hypothesis that trypsin activates a mechanism allowing for local release of sensory neurokinins from afferent C-fibers and that this release occurs independently of the sensory function of these nerves.
Differentiation of Convulsive Syncope and Epilepsy with Head-Up Tilt Testing
Authors: Blair P. Grubb, Gary Gerard, Kenneth Roush, Peter Temesy-Armos, Laura Elliott, Harry Hahn, Claudia Spann
Journal: Annals of Internal Medicine (1991)

To evaluate the usefulness of head-upright tilt table testing in the differential diagnosis of convulsive syncope from epileptic seizures in patients with recurrent idiopathic seizure-like episodes.Prospective, nonrandomized study.Electrophysiology laboratory of a university hospital.Fifteen patients (8 men and 7 women patients; mean age, 29 +/- 20 years) with recurrent unexplained seizure-like episodes, unresponsive to antiseizure medication.Head-upright tilt table testing with or without isoproterenol infusion. Five patients who were initially tilt positive had a second tilt test with continuous electroencephalographic (EEG) recording.Syncope associated with tonic-clonic seizure-like activity occurred in six patients (40%) during the baseline tilt and in four patients (27%) during isoproterenol infusion (total positive tests, 67%). The EEG showed diffuse brain wave slowing (not typical of epileptic seizures) in five of five patients during the convulsive episode. All patients who had positive test results eventually become tilt table negative after therapy, and over a mean follow-up period of 21 +/- 2 months, no further seizure-like episodes have occurred.Upright tilt table testing combined with isoproterenol infusion may be useful to distinguish convulsive syncope from epileptic seizures.
The mechanical stimulation of cells in 3D culture within a self-assembling peptide hydrogel
Authors: Yusuke Nagai, Hidenori Yokoi, Keiko Kaihara, Keiji Naruse
Journal: Biomaterials (2011)

The aim of this present study was to provide a scaffold as a tool for the investigation of the effect of mechanical stimulation on three-dimensionally cultured cells. For this purpose, we developed an artificial self-assembling peptide (SPG-178) hydrogel scaffold. The structural properties of the SPG-178 peptide were confirmed by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and transmission electron microscopy (TEM). The mechanical properties of the SPG-178 hydrogel were studied using rheology measurements. The SPG-178 peptide was able to form a stable, transparent hydrogel in a neutral pH environment. In the SPG-178 hydrogel, mouse skeletal muscle cells proliferated successfully (increased by 12.4 ± 1.5 times during 8 days of incubation; mean ± SEM). When the scaffold was statically stretched, a rapid phosphorylation of ERK was observed (increased by 2.8 ± 0.2 times; mean ± SEM). These results demonstrated that the developed self-assembling peptide gel is non-cytotoxic and is a suitable tool for the investigation of the effect of mechanical stimulation on three-dimensional cell culture.
Pollution in Paris causes problems
Authors: A Dorozynski
Journal: BMJ (1994)

Atmospheric pollution by nitrogen dioxide, a byproduct of vehicle exhausts, in Paris and its suburbs increases by 15-20% the number of people who need to be admitted to hospital for asthma A new survey also shows that atmospheric sulphur dioxide, produced mainly by industry and heating, increases mortality from cardiovascular disease by a tenth.

The survey, carried out by the Observatory for Health …
An Address on THE CONSTITUTIONAL FACTOR IN DISEASE: BLOOD PRESSURE AND CONSTITUTION
Authors: A. F. Hurst
Journal: BMJ (1927)

Treatment.In advanced cases medi6al and general treatment is ilndicated, as surgery offers little prospect of cure, but when the disease is limited to the epididymis and seminal vesicle radical operation is indicated.It should consist of removal cm bloc of the epididymis (or epididyrmis and testis), the vas doferens, the seminal vesicle, and wheni necessary a portion or the whole of the prostate.The operation can.be accomplished through an inguinal incision by Loughnane's method, but if the prostate is involved Young's combined inguino-perinleal method is necessary.Should tho disease be secondary to unilateral renal tuberculosis the affected kidney must be removed firsi and the operation on the genital tract postponed to a later date.In all cases tuberculin is of great value, but only after operation.In my experience it has not the least effect on well established urogenital tuberculosis, and should never take the place of surgery if removal of the disease is possible.
Concentrations of plasminogen activator inhibitor type1 (PAI-I) and urokinase-type plasminogen aktivator (uPA) in primary breast cancer (BC) tissue and corresponding axillary lymph node metastasis.
Authors: A Artmann, K Celik, M Kiechle, EJ Rummeny, M Schmitt, N Harbeck
Journal: Cancer Research (2009)

Abstract Abstract #2046 Background: Components of the plasminogen activator system play a key role in tumor invasion and metastasis. Tumor tissue levels of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 showed a strong prognostic impact in node-negative and node-positive primary BC. uPA/PAI-1 were the first novel prognostic factors in primary BC reaching the highest level of evidence for their clinical utility and they have recently been recommended by ASCO for clinical decision making.&amp;#x2028; Material and Methods: For the first time, correlations between uPA and PAI-1 concentrations in 73 primary tumor tissues and corresponding axillary lymphnodes (ALN) in node-negative (pN0) and node-positive (pN+) BC (1991-98) and their prognostic impact on disease-free (DFS) and overall survival (OS) were evaluated.&amp;#x2028; Results: Median follow-up was 56 months. Overall, PAI-I (p=0,014) and uPA concentrations (p&amp;lt;0,001) were significantly higher in tumour tissue than in the corresponding ALN. There was no significant difference of PAI-1 in primary tumor tissue between pN0 and pN+ disease. In involved ALN (pN+), concentrations of PAI-1 but not of uPA, were significantly higher than in pN0 (p&amp;lt;0.001). Moreover, patients with higher PAI-1 concentrations in the corresponding ALN than in their primary tumor had a significantly shorter DFS (p&amp;lt;0,001) and OS (p=0.005).&amp;#x2028; Discussion: Our clinical findings support the basic research data implicating uPA and PAI-1 as key proteolytic factors in metastasis-asociated processes such as adhesion, angiogenesis, invasion, proliferation and migration. For the first time, we are able to demonstrate that particularly PAI-1 seems to be involved in tumor metastasis in primary breast cancer with its concentrations being higher in involved ALN than in the primary tumor. Besides uPA/PAI-1 being validated and clinically useful prognostic factors, interference with the uPA/PAI-1 system thus promises to be an interesting therapeutic concept in BC. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2046.