tbuckley/cabot-search huggingface dataset:
Epac1-dependent phospholamban phosphorylation mediates the cardiac response to stresses
Authors: Satoshi Okumura, Takayuki Fujita, Wenqian Cai, Meihua Jin, Iyuki Namekata, Yasumasa Mototani, Huiling Jin, Yoshiki Ohnuki, Yayoi Tsuneoka, Reiko Kurotani, Kenji Suita, Yuko Kawakami, Shogo Hamaguchi, Takaya Abe, Hiroshi Kiyonari, Takashi Tsunematsu, Yunzhe Bai, Sayaka Suzuki, Yuko Hidaka, Masanari Umemura, Yasuhiro Ichikawa, Utako Yokoyama, Motohiko Sato, Fumio Ishikawa, Hiroko Izumi-Nakaseko, Satomi Adachi-Akahane, Hikaru Tanaka, Yoshihiro Ishikawa
Journal: Journal of Clinical Investigation (2014)

PKA phosphorylates multiple molecules involved in calcium (Ca2+) handling in cardiac myocytes and is considered to be the predominant regulator of β-adrenergic receptor–mediated enhancement of cardiac contractility; however, recent identification of exchange protein activated by cAMP (EPAC), which is independently activated by cAMP, has challenged this paradigm. Mice lacking Epac1 (Epac1 KO) exhibited decreased cardiac contractility with reduced phospholamban (PLN) phosphorylation at serine-16, the major PKA-mediated phosphorylation site. In Epac1 KO mice, intracellular Ca2+ storage and the magnitude of Ca2+ movement were decreased; however, PKA expression remained unchanged, and activation of PKA with isoproterenol improved cardiac contractility. In contrast, direct activation of EPAC in cardiomyocytes led to increased PLN phosphorylation at serine-16, which was dependent on PLC and PKCε. Importantly, Epac1 deletion protected the heart from various stresses, while Epac2 deletion was not protective. Compared with WT mice, aortic banding induced a similar degree of cardiac hypertrophy in Epac1 KO; however, lack of Epac1 prevented subsequent cardiac dysfunction as a result of decreased cardiac myocyte apoptosis and fibrosis. Similarly, Epac1 KO animals showed resistance to isoproterenol- and aging-induced cardiomyopathy and attenuation of arrhythmogenic activity. These data support Epac1 as an important regulator of PKA-independent PLN phosphorylation and indicate that Epac1 regulates cardiac responsiveness to various stresses.
Lyme-Disease Meningitis Treated with Tetracycline
Authors: ALEXANDER ACKLEY
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 October 1986Lyme-Disease Meningitis Treated with TetracyclineALEXANDER ACKLEY JR., M.D., MICHAEL LUPOVICI, M.D.ALEXANDER ACKLEY JR., M.D.Search for more papers by this author, MICHAEL LUPOVICI, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-105-4-630_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The recommended treatment for patients with neurologic abnormalities of Lyme disease is high-dose intravenous penicillin (1). There is no published experience with other antibiotics. Because of the increasing incidence of Lyme disease, it can be anticipated that occasional patients with meningitis and a history of an allergic reaction to penicillin will have to be treated with an alternative antibiotic. We had one such patient whom we treated with tetracycline.A 28-year-old man camped overnight in the woods of Cape May, New Jersey, in late May 1985. He did not recall a tick bite. On 8 June, he...Reference1. STEEREPACHNERMALAWISTA AAS. Neurologic abnormalities of lyme disease: successful treatment with high-dose intravenous penicillin. Ann Intern Med. 1983;99:767-72. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Medical Center at Princeton Princeton, NJ 08540 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByEffectiveness of antimicrobial treatment against Borrelia burgdorferi infection in miceTherapy of Lyme NeuroborreliosisDie Lyme-Borreliose (Eine Übersicht)Chloramphenicol and Tetracyclines 1 October 1986Volume 105, Issue 4Page: 630-631KeywordsAllergy and immunologyAntibioticsLyme diseaseMeningitisPatientsPenicillinTetracyclinesTicks Issue Published: 1 October 1986 PDF DownloadLoading ...
Changes in intracellular calcium during mechanical alternans in isolated ferret ventricular muscle.
Authors: M J Lab, J A Lee
Journal: Circulation Research (1990)

Alternans in heart is important as pulsus alternans in cardiac failure and electrophysiological alternans in myocardial ischemia. The explanation of this phenomenon is still unclear. We attempted to investigate the cellular mechanisms of alternans by measuring intracellular free calcium concentration [( Ca2+]i) with the photoprotein aequorin in isolated ferret papillary muscles. Tension and length were also recorded simultaneously. Transient mechanical alternans lasting five to 20 contractions could be reliably induced in this preparation by following a 30-second rest period with stimulation at a fast rate (2-4 Hz). Production of sustained mechanical alternans, which lasted longer than 20 contractions and could persist for several hundred contractions, required additional interventions, consisting of a lower temperature (25 degrees C), a lower external calcium concentration (1 mM), and a lower pH (6.91) than control conditions (0.33-0.5 Hz, 30 degrees C, 2 mM Ca2+, pH 7.36). Transient mechanical alternans was associated with transient in-phase alternation of aequorin light and, hence, [Ca2+]i. Sustained mechanical alternans was associated with sustained in-phase alternation of aequorin light as well as incomplete relaxation of tension. However, when muscles were switched from isometric to unloaded isotonic contraction, relaxation between stimuli was complete but contraction and the aequorin light signal continued to alternate. The addition of 10 mM caffeine or 10 microns ryanodine abolished transient and sustained mechanical alternans and also abolished the associated alternation of aequorin light. Commensurate with the action of ryanodine, which allows the sarcoplasmic reticulum to reaccumulate calcium to a limited extent after a period of rapid stimulation, sustained mechanical alternans sometimes reappeared in an attenuated form 30 to 50 contractions after the addition of ryanodine. These results demonstrate that incomplete muscle relaxation between beats need not be present for alternans to occur, and support the hypothesis that alternans is caused by intracellular calcium cycling involving the sarcoplasmic reticulum.
PRESSOR SUBSTANCES FROM THE BODY FLUIDS OF MAN IN HEALTH AND DISEASE
Authors: Irvine H. Page
Journal: The Journal of Experimental Medicine (1935)

1. Extracts of human blood plasma, ascitic and cerebrospinal fluids have been shown to contain a substance or substances which have a prolonged and powerful pressor action when injected into test animals. 2. The chemical properties of the substance suggest those of an organic base. It is extracted with alcohol, soluble in water and acetone, extracted from water by chloroform, and probably is but slightly heat-stable. The plasma colloids seem to hold the substance in a bound state since it does not appear in the ultrafiltrate and is liberated on coagulation of the colloids by alcohol. Coagulation alone of the blood does not cause the substance to be formed. 3. Its action suggests that its pressor effect is brought about by mediation of the central nervous system. This inference was drawn from the following observations. (a) The functional intactness of the central nervous system is essential in order that pressor responses be obtained. Unanesthetized animals exhibit greater vascular responses than do anesthetized. (b) Pithing animals completely abolishes the response. Progressive ablation of the brain to the level of the hind brain does not alter the response, but below this level, injury abolishes the activity of the extract. (c) Some substance in the extract sensitizes the mechanism responsible for the carotid sinus reflex. (d) There is no parallelism between the response to peripherally acting drugs and pressor extracts. (e) Removal of the adrenal glands does not affect its character. 4. The rise in blood pressure appears to be due especially to constriction of the arteries in the splanchnic region. 5. Assay of the pressor extracts is made difficult because of the dependence of the vascular response on the functional state of the central nervous system. The carotid sinus reflex and stimulation with carbon dioxide-air mixtures have proved most useful means for the estimation of this functional state. It has been pointed out that the vascular responses to extract, stimulation of the carotid sinus, and inhalation of carbon dioxide-air vary greatly during the course of an experiment on anesthetized animals. This natural history of the vascular responses has been described. 6. No evidence has been produced by the method employed that the amount of this pressor substance is increased in the blood or spinal fluid of patients with hypertension of varied pathogenesis (nephritic hypertension, essential hypertension, malignant hypertension, eclampsia, and pituitary basophilism).
Risk Factors For Distal Symmetric Neuropathy in NIDDM: The San Luis Valley Diabetes Study
Authors: Gary M Franklin, Susan M Shetterly, Jeffrey A Cohen, Judith Baxter, Richard F Hamman
Journal: Diabetes Care (1994)

To investigate risk factors for distal symmetric (sensory) neuropathy among prevalent cases of non-insulin-dependent diabetes mellitus (NIDDM) in a population-based study in southern Colorado.Prevalent neuropathy was identified in 77 of 277 people with NIDDM by a standardized history and neurologic examination. Fifteen known or suspected risk factors for neuropathy were determined without knowledge of neuropathy status.Older age at examination, longer duration of diabetes, higher glycohemoglobin percentage, lower fasting C-peptide, insulin use, and presence of retinopathy and nephropathy (microalbumin > or = 200 micrograms/ml) were all significantly associated with neuropathy. Sex, ethnicity (Hispanic versus non-Hispanic white), height, systolic blood pressure, peripheral vascular disease, cigarette and alcohol use, and serum lipid levels were not significantly associated with neuropathy. In a multivariate logistic model, increasing age (odds ratio [OR] = 1.3, 95% confidence interval [CI] = 1.1-1.6), longer duration of diabetes (OR = 1.3, CI = 1.0-1.6), increased glycohemoglobin percentage (OR = 1.5, CI = 1.1-2.1), and insulin use (OR = 2.8, CI = 1.3-6.1) were associated with neuropathy. Retinopathy (OR = 3.0, CI = 1.2-7.7), but not nephropathy, was important when added to this model.Worse glycemic control and insulin use were independently associated with neuropathy in people with NIDDM. Whether insulin use represents another marker for severity of the metabolic disturbance or is an independent risk factor for neuropathy requires further study. We could not confirm associations of neuropathy with height, with nephropathy, or with retinopathy, independent of duration of diabetes.
Hemoglobin level and survival in hemodialysis patients with polycystic kidney disease and the role of administered erythropoietin
Authors: Anuja Shah, Miklos Z. Molnar, Lilia R. Lukowsky, Joshua J. Zaritsky, Csaba P. Kovesdy, Kamyar Kalantar‐Zadeh
Journal: American Journal of Hematology (2012)

Interventional trials indicate adverse outcomes when hemoglobin >13 g/dL is targeted in patients with chronic kidney disease (CKD) who receive erythropoiesis-stimulating agents (ESAs). It is not clear whether high-achieved hemoglobin with minimal to no ESA administration as observed in some patients with polycystic kidney disease (PKD) is also associated with poor outcomes. Survival models were examined to assess the association between hemoglobin increments and mortality in a 6-year cohort of 2,402 PKD and 110,875 non-PKD hemodialysis patients across infrequent versus frequent ESA therapy defined as ESA < 25% of cohort time versus otherwise, respectively. Mortality risk was estimated by Cox proportional regression [hazard ratio (HR) and 95% of confidence interval] analysis. Patients with PKD were aged 58 ± 13 years and included 46% women 14% Blacks, respectively. Fully adjusted death HRs of time-averaged hemoglobin increments <11.0, 12.0 to <13.0 g/dL (reference: 11.0 to <12.0 g/dL) for frequent ESA therapy were 2.57 (1.48-4.48), 0.60 (0.43-0.82), and 0.81 (0.50-1.29), whereas for infrequent ESA therapy they were 1.33 (0.47-3.78), 0.28 (0.13-0.61), and 0.22 (0.09-0.57), respectively. Hence, in patients with PKD who require infrequent ESA, incrementally higher achieved hemoglobin including > 13.0 g/dL exhibits better survival; this incremental survival gain of higher hemoglobin is not observed in patients with PKD receiving frequent ESA administration, in whom hemoglobin concentration > 13 exhibits increased mortality.
Advancing hip and groin injury management: from eminence to evidence
Authors: Kristian Thorborg, Per Hölmich
Journal: British Journal of Sports Medicine (2013)

Hip and groin injuries include multiple, complex and long-standing conditions.1–3 Many treatment approaches and techniques, primarily investigated in case series (Level-4 evidence)4 for athletes with long-standing hip and groin injury, have continuously emerged and resurfaced during the last 30 years.5–9 These case series often claim to have a treatment success close to 100%, and to initiate a fast return to sport.10–15 These successful return rates, however, seldom match athletes and sports practitioners’ own experience as long-standing hip and groin injuries are often extremely difficult to recover from.1–3 ,16 ,17 

The lack of reliable, valid and responsive outcome measures for patients with hip and groin injuries has, in our opinion, been one of the main reasons why very few treatment advances have been made within this field.5–9 ,18 ,19 While some existing treatments (based on case series) may have promise, their success has mostly been evaluated by treatment providers (often the operating surgeon and main author), instead of being evaluated by the treatment receivers (the patients). This makes it very difficult to get a true impression of these procedures’ potential effect. It is possible that patients’ perceptions of the treatment success of these interventions are entirely different from those of the treatment providers.20 

However, with the recent development of reliable, valid and responsive outcome scores, such as the Copenhagen Hip And Groin Outcome Score,19 ,21 it is now possible to objectively evaluate patient-reported hip and groin symptoms and function.19 Furthermore, the development of reliable clinical tests, including hip strength, squeeze tests22–26 and specific hip range of motion tests,22 ,27 makes it possible to measure  some of the clinical impairments frequently presenting in this patient group.22 ,27–30 Further research into specific strength testing positions …
Clinical Correlates and Heritability of Flow-Mediated Dilation in the Community
Authors: Emelia J. Benjamin, Martin G. Larson, Michelle J. Keyes, Gary F. Mitchell, Ramachandran S. Vasan, John F. Keaney, Birgitta T. Lehman, Shuxia Fan, Ewa Osypiuk, Joseph A. Vita
Journal: Circulation (2004)

Background— Studies in selected samples have linked impaired endothelial function with cardiovascular disease and its risk factors. The clinical correlates and heritability of endothelial function in the community have not been described. Methods and Results— We examined a measure of endothelial function, brachial artery flow-mediated dilation (FMD), expressed as both percent (FMD%) and actual dilation by ultrasound with the occlusion cuff below the elbow in 2883 Framingham Study participants (52.9% women; mean age, 61 years). A subset of 1096 participants performed a 6-minute walk test before FMD determination. Mean FMD% was 3.3±3.0% in women and 2.4±2.4% in men. In stepwise multivariable linear regression models, FMD% was inversely related to age, systolic blood pressure, body mass index (BMI), lipid-lowering medication, and smoking, whereas it was positively related to female gender, heart rate, and prior walk test. The estimated heritability of FMD% was 0.14. FMD actual dilation findings were similar, except that female sex and BMI were not significantly associated. Conclusions— Increasing age, systolic blood pressure, BMI, and smoking were associated with lower FMD% in our community-based sample, whereas prior exercise and increasing heart rate were associated with higher FMD%. The estimated heritability of FMD was modest. Future research will permit more complete characterization of the genetic and environmental determinants of endothelial function and its prognostic value in the community.
Demonstration of PDGF B-chain mRNA in glomeruli in mesangial proliferative nephritis by in situ hybridization
Authors: Ashio Yoshimura, Kathy Gordon, Charles E. Alpers, Jürgen Floege, Pam Pritzl, Russell Ross, William G. Couser, Daniel F. Bowen-Pope, Richard J. Johnson
Journal: Kidney International (1991)
ADMINISTRATION OF THIONIN AND METHYL VIOLET IN INTESTINAL BRUCELLA INFECTION
Authors: HUGH R. LEAVELL
Journal: JAMA (1930)

The notably unsatisfactory state of our knowledge of the treatment of undulant fever makes any contribution that seems at all hopeful worthy of further consideration. It is with this in mind that our present method of treating cases is presented, in the hope that it may be tried in resistant cases elsewhere. The description by Amoss and Poston<sup>1</sup>of a method for isolating<i>Brucella</i>from the stools has made it possible to follow the results of treatment. Several of our cases have persistently shown<i>Brucella abortus</i>in the stools for long periods and after cultures from the blood and other body fluids had become negative. This has been true even when the blood serum showed a low agglutinin titer for<i>Brucella abortus</i>, and consequently the stool culture in these cases was the only method by which a positive diagnosis could be made. Huddleson<sup>2</sup>described the use of methyl
Stress Fractures of the Metatarsals in Childhood
Authors: E. C. McClure
Journal: BMJ (1947)

In the surgery of dyspepsia-and surgery is frequently required-it is essential in many cases that pre-operative treat- ment be often long and even trying, and it was this featUire that led me in my search to discover the value of bromide combined with cther aids in the treatment of dyspepsia.-Iam, etc., Dundee.
Likelihood Analysis of Phylogenetic Networks Using Directed Graphical Models
Authors: Korbinian Strimmer, Vincent Moulton
Journal: Molecular Biology and Evolution (2000)

A method for computing the likelihood of a set of sequences assuming a phylogenetic network as an evolutionary hypothesis is presented. The approach applies directed graphical models to sequence evolution on networks and is a natural generalization of earlier work by Felsenstein on evolutionary trees, including it as a special case. The likelihood computation involves several steps. First, the phylogenetic network is rooted to form a directed acyclic graph (DAG). Then, applying standard models for nucleotide/amino acid substitution, the DAG is converted into a Bayesian network from which the joint probability distribution involving all nodes of the network can be directly read. The joint probability is explicitly dependent on branch lengths and on recombination parameters (prior probability of a parent sequence). The likelihood of the data assuming no knowledge of hidden nodes is obtained by marginalization, i.e., by summing over all combinations of unknown states. As the number of terms increases exponentially with the number of hidden nodes, a Markov chain Monte Carlo procedure (Gibbs sampling) is used to accurately approximate the likelihood by summing over the most important states only. Investigating a human T-cell lymphotropic virus (HTLV) data set and optimizing both branch lengths and recombination parameters, we find that the likelihood of a corresponding phylogenetic network outperforms a set of competing evolutionary trees. In general, except for the case of a tree, the likelihood of a network will be dependent on the choice of the root, even if a reversible model of substitution is applied. Thus, the method also provides a way in which to root a phylogenetic network by choosing a node that produces a most likely network.
STUDIES ON PNEUMOCOCCUS GROWTH INHIBITION
Authors: Oswald H. Robertson, Richard H. P. Sia
Journal: The Journal of Experimental Medicine (1924)

Using the method described in an earlier publication for testing the growth-inhibitory and bactericidal activity of serum-leucocyte mixtures for the pneumococcus, a study has been made of the action of antipneumococcus serum added to the serum and leucocytes of the rabbit, which alone lack the power to inhibit pneumococcus growth. It was found that the additiori of relatively small quantities of immune serum to a mixture of rabbit serum and washed rabbit leucocytes conferred on this mixture marked growth-inhibitory and pneumococcidal powers. The effect of the immune serum was found to be quantitative in nature. Beyond a certain point progressive dilution of the serum resulted in a corresponding decrease in the degree of growth inhibition, but this property of the immune serum did not disappear until a high dilution was reached. The leucocytes were also found to exert their effect quantitatively. Within certain limits the number of pneurnococci killed was dependent on the quantity of them present. Tests comparing the action of immune serum in the rabbit serum-leucocyte tubes with their protective action in mice showed a close parallelism between these two effects; that is to say, an immune serum showing marked protective properties for mice was likewise effective in high dilution in the in vitro test, and vice versa.
Transfusion-Induced Enterobacter Sepsis
Authors: John V. Bennett
Journal: New England Journal of Medicine (1971)

Transfusion reactions caused by blood contaminated with bacteria introduced at the time of collection have long been recognized. Such contamination represents a potential hazard with all blood products, but the likelihood is greatly increased when the contributions of several donors are pooled. The article by Buchholz et al. in this issue of the Journal reports a surprisingly high frequency of contamination in platelet pools and clearly documents yet another blood-product vehicle of transmission of clinically important infections.In addition to infections resulting from external contamination of blood products, the unwitting transmission of serum hepatitis, malaria, cytomegalovirus and other infections directly . . .
Whole-exome sequencing links caspase recruitment domain 11 (CARD11) inactivation to severe combined immunodeficiency
Authors: Johann Greil, Tobias Rausch, Thomas Giese, Obul R. Bandapalli, Volker Daniel, Isabelle Bekeredjian-Ding, Adrian M. Stütz, Christoph Drees, Susanne Roth, Jürgen Ruland, Jan O. Korbel, Andreas E. Kulozik
Journal: Journal of Allergy and Clinical Immunology (2013)