tbuckley/cabot-search huggingface dataset:
Antibodies against low-density lipoprotein receptor–related protein 4 induce myasthenia gravis
Authors: Chengyong Shen, Yisheng Lu, Bin Zhang, Dwight Figueiredo, Jonathan Bean, Jiung Jung, Haitao Wu, Arnab Barik, Dong-Min Yin, Wen-Cheng Xiong, Lin Mei
Journal: Journal of Clinical Investigation (2013)

Myasthenia gravis (MG) is the most common disorder affecting the neuromuscular junction (NMJ). MG is frequently caused by autoantibodies against acetylcholine receptor (AChR) and a kinase critical for NMJ formation, MuSK; however, a proportion of MG patients are double-negative for anti-AChR and anti-MuSK antibodies. Recent studies in these subjects have identified autoantibodies against low-density lipoprotein receptor-related protein 4 (LRP4), an agrin receptor also critical for NMJ formation. LRP4 autoantibodies have not previously been implicated in MG pathogenesis. Here we demonstrate that mice immunized with the extracellular domain of LRP4 generated anti-LRP4 antibodies and exhibited MG-associated symptoms, including muscle weakness, reduced compound muscle action potentials (CMAPs), and compromised neuromuscular transmission. Additionally, fragmented and distorted NMJs were evident at both the light microscopic and electron microscopic levels. We found that anti-LRP4 sera decreased cell surface LRP4 levels, inhibited agrin-induced MuSK activation and AChR clustering, and activated complements, revealing potential pathophysiological mechanisms. To further confirm the pathogenicity of LRP4 antibodies, we transferred IgGs purified from LRP4-immunized rabbits into naive mice and found that they exhibited MG-like symptoms, including reduced CMAP and impaired neuromuscular transmission. Together, these data demonstrate that LRP4 autoantibodies induce MG and that LRP4 contributes to NMJ maintenance in adulthood.
A New Scanning Method for Thallium-201 Myocardial SPECT: Semidecubital Position Method
Authors: AKIO SUZUKI, SEIJI MUTO, MOTOO OSHIMA, HIROSHI SAITO, SHUHEI YAMAMOTO, MITSUHIRO YOKOTA, HIROSHI HAYASH
Journal: Clinical Nuclear Medicine (1989)

The authors have developed a new scanning method for Tl-201 myocardial SPECT using a rotating gamma camera with 180-degree data collection. This requires a new type of imaging table on which the patient is placed in a 50-degree right semidecubital position to allow close proximity to the camera-collimator system. Using this method, attenuation by the imaging table is completely avoidable because the projected views in the left oblique directions are not obstructed by the table. In addition, the radius of camera rotation is about 25% shorter than in the conventional method. Phantom and 16 clinical studies were performed to compare the performance of conventional and semidecubital position methods. In phantom studies, tomographic images produced using the new method showed better lesion contrast and more counts in the posteroinferior wall of the heart than those produced using the conventional method. Clinically, 12 of the 16 studies showed more counts in the posteroinferior wall of the heart with the semidecubital position method than with the conventional method. The semidecubital position method is useful for Tl-201 myocardial SPECT, especially for evaluation of posteroinferior wall hypoperfusion.
Implanted cardiac pacemakers: Experience with electronic testing
Authors: D. Smith, R. McDonald, G. Sloman
Journal: Cardiovascular Research (1971)

Seventy patients with implanted cardiac pacemakers have been followed in a special pacemaker clinic for periods up to five years. A system of electronic testing has been used after implanting 142 generators. Analysis of the stimulus artefact made it possible to predict generator failure in the majority of systems. In those pacemakers where the failure could be predicted, the fault was always associated with the battery supply. It was not possible to predict sudden electronic component failure. In order to use the generator's full resources and minimize unexpected battery failure, regular electronic testing is recommended.
Minimal evidence of platelet and endothelial cell reactive antibodies in thrombotic thrombocytopenic purpura
Authors: Thomas J. Raife, Bonnie Atkinson, Richard H. Aster, Janice G. McFarland, Jerome L. Gottschall
Journal: American Journal of Hematology (1999)

Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterized by microvascular thrombosis with thrombocytopenia and end-organ injury. Evidence suggests that platelet or endothelial cell injury may be initial pathological events in TTP. A number of factors in patient plasma, including immunoglobulins, have been proposed to mediate cellular injury in TTP. However, systematic analyses of TTP patient plasma for the presence of platelet or endothelial cell antibodies are lacking. We, therefore, analyzed 48 TTP patient plasma samples for the presence of platelet and endothelial cell antibodies by using enzyme-linked immunosorbent assay, flow cytometry, and microlymphocytotoxicity. Twelve of 48 TTP patient samples (25%) reacted against purified platelet glycoproteins. Nine (19%) also contained antibodies that bound to allogeneic target platelets in flow-cytometric assays. Nine of 48 samples (19%) contained antibodies to human umbilical vein endothelial cells in flow-cytometric assays, and seven of 48 patient samples (15%) bound to human dermal microvascular endothelial cells. Six of 48 (13%) patient plasma samples contained antibodies that bound to human umbilical vein endothelial cells activated with γ-interferon and tumor necrosis factor-α. Of twenty samples that were reactive in one or more platelet or endothelial cell assay, eight contained human leukocyte antigen antibodies reactive in microlymphocytotoxicity. These studies demonstrate that antibodies reactive against platelet or endothelial cell antigens are not prevalent in TTP, and that more than a third of antibodies detected are human leukocyte antigen alloantibodies. Our findings suggest that autoantibodies against platelets or endothelial cells are not important in the pathogenesis of this syndrome. Am. J. Hematol. 62:82–87, 1999. © 1999 Wiley-Liss, Inc.
Predicting cancer drivers: are we there yet?
Authors: Vidhya G Krishnan, Pauline C Ng
Journal: Genome Medicine (2012)

Genomic variants with a key role in causing cancer or affecting the response to cancer therapeutics need to be identified so that they can be targeted for therapy. The transFIC tool aims to identify somatic point mutations that drive cancer in sequencing projects. This package is available as a web service, a stand-alone program and a website. It improves the functional prediction scores generated by popular established prediction tools and will be useful to cancer researchers.http://genomemedicine.com/content/4/11/89.
Dacron conduit with a stented porcine xenograft valve in the anatomic correction of transposition of the great arteries and subpulmonary stenosis.
Authors: L Gonzalez-Lavin, A W Sparrow
Journal: Thorax (1975)

A stented porcine xenograft valve, sutured into a woven Dacron tubular graft, has been used in the anatomic correction of D-loop, D-transposition of the great arteries, and subpulmonary stenosis. The main advantage of this technique is its simplicity and practicality, as both Dacron tubular grafts and stented porcine xenograft valves are commercially available.
Isolation of specific and biologically active peptides that bind cells from patients with acute myeloid leukemia (AML)
Authors: Naomi Galili, Emmanuelle Devemy, Azra Raza
Journal: Journal of Hematology & Oncology (2008)

In a departure from conventional strategies to improve treatment outcome for myeloid malignancies, we report the isolation of leukemia-specific peptides using a phage display library screened with freshly obtained human myeloid leukemia cells. A phage display library was screened by 5 rounds of biopanning with freshly isolated human AML cells. Individual colonies were randomly picked and after purification, biologic activity (growth and differentiation) on fresh AML cells was profiled. Ten peptides were synthesized for further biological studies. Multiple peptides were found to selectively bind to acute myeloid leukemia (AML) cells. The peptides bound to leukemia cells, were internalized and could induce proliferation and/or differentiation in the target patient cells. Two of the peptides, HP-A2 and HP-G7, appeared to have a novel mechanism of inducing differentiation since they did not cause G1 arrest in cycling cells even as the expression of the differentiation marker CD11b increased. Peptide induced differentiation of leukemia cells offers a novel treatment strategy for myeloid malignancies, whereas their ability to induce proliferation could be harnessed to make cells more sensitive to chemotherapy. Conceptually, these leukemia specific peptides can also be used to refine diagnosis, document minimal residual disease, and selectively deliver toxins to malignant cells.
Mark Ryan, the Fenian
Authors: Henry M. Gahan
Journal: New England Journal of Medicine (1960)

MARK Ryan was born in the Parish of Kilconly, Galway, Ireland, on November 10, 1844. His early years were lived during the days of oppression and terrible famine.For the peasants, life was an uphill struggle, almost from the cradle to the grave, and the Fenian movement brought life and hope to them. Ryan had a deep interest in his country's history. As a boy he worked on his father's farm in Kilconly and led an active outdoor life. Later, he studied at Queen's College, Galway, and then went to Dublin and attended Ledwidge College, where he studied anatomy and . . .
Statistical Report of All Operations Performed on Healthy Joints in Hospital Practice by Mr. Lister From September 1871
Authors: W. W. Cheyne
Journal: BMJ (1879)

posterior cornua of grey matter, is the external band of the posterior column; it is also called the posterior root-zone.Sclerosis of the inner division of the posterior column-the column of Goll-does not appear to give rise to the characteristic phenomena of this disease; while it is always present when the posterior root-zones are affected.Dr. J. Lockhart Clarke has further demonstrated that to the posterior root-zones are principally attached the posterior or sensory roots of the spinal nerves, not to the lateral columns, as was once believed.Usually the posterior cornua of grey matter are to some extent implicated in the sclerosis.The posterior roots of the spinal nerves are almost always found to be atrophied.Similar alterations from degeneration are found in parts within the cranium, which are closely related to the posterior columns of the cord; as, for example, in the lower cerebral peduncles, the restiform bodies, and the optic thalami.The optic nerve is often affected, and the grey degeneration in it may often be detected very early in the disease by means of the ophthalmoscope.Chronic neuritis-the result of implication of the cilio-spinal centre, upon which also depends the contraction of the pupil in these cases- is also frequently met with in this as in other spinal diseases.You must not expect to find the disease always strictly limited to the posterior root-zones and the adjacent grey matter of the spinal cord.Other regions are often invaded in the progress of the disease, and you will then have contractions, paralysis, atrophy, or disease of joints superadded, according to the region involved.[To be conztinuted.]
Apical ballooning and cardiomyopathy in a melanoma patient treated with ipilimumab: a case of takotsubo-like syndrome
Authors: Benjamin P Geisler, Roy A Raad, Diana Esaian, Elad Sharon, David R Schwartz
Journal: Journal for ImmunoTherapy of Cancer (2015)

Although animal studies have shown that the immunomodulator ipilimumab causes inflammation of the myocardium, clinically significant myocarditis has been observed only infrequently. We report a case of suspected acute coronary syndrome without a culprit lesion on cardiac angiography and takotsubo cardiomyopathy (TC)-like appearance on echocardiography in a patient with metastatic melanoma who received four standard doses of ipilimumab. Apical ballooning, hyperdynamic basal wall motion, systolic anterior motion of the mitral valve, and associated severe left ventricular outflow tract obstruction were present. Restaging with positron emission tomography-computed tomography done soon after discharge incidentally revealed increased fludeoxyglucose uptake in the apex. This case illustrates that a TC-like syndrome might be caused by autoimmune myocarditis after ipilimumab treatment although this was not biopsy-confirmed. Post-marketing surveillance should capture cardiac events occurring in patients treated with ipilimumab to better document and clarify a relationship to the drug, and biopsies should be considered. Physicians utilizing this novel agent should be aware of the potential for immune-related adverse events.
Mechanism responsible for the antitumor effect of BCG-CWS using the LEEL method in a mouse bladder cancer model
Authors: Takashi Nakamura, Masafumi Fukiage, Yoshiteru Suzuki, Ikuya Yano, Jun Miyazaki, Hiroyuki Nishiyama, Hideyuki Akaza, Hideyoshi Harashima
Journal: Journal of Controlled Release (2014)
Optimal duration of exclusive breast feeding in low income countries
Authors: R. E Black
Journal: BMJ (2002)

Breast feeding continues to be the norm in low income countries, but the period of exclusive breast feeding after birth is often short.w1 Accumulating evidence of the benefits of exclusive breast feeding led to a recommendation by the World Health Organization that it be done for the first six months of life,1 consistent with a previous recommendation by Unicef. This guidance seems to be based on accumulated evidence.

Observational studies in low income populations, even in tropical settings, have shown that fluids in addition to breast milk are unnecessary to maintain hydration.2 Furthermore, the addition of water, tea, or other liquids has adverse effects on the output of breast milk, growth, and morbidity and mortality due to infectious diseases.3 w2 A reanalysis of studies in Brazil and Bangladesh has found that breastfed infants in the first six months of life who were given additional foods had a twofold to threefold higher mortality from diarrhoea and pneumonia …
Bombesin-induced gastrin release from canine G cells is stimulated by Ca2+ but not by protein kinase C, and is enhanced by disruption of rho/cytoskeletal pathways.
Authors: R Seensalu, D Avedian, R Barbuti, M Song, L Slice, J H Walsh
Journal: Journal of Clinical Investigation (1997)

Isolated canine G cells in primary culture have been used to study calcium, protein kinase C (PKC), and rho/cytoskeletal-dependent intracellular pathways involved in bombesin- stimulated gastrin release. A method to obtain highly purified G cells by culture (64% G cells) after flow cytometry on elutriated fractions of cells from digested canine gastric antral mucosa has been developed. Pretreatment of G cells with thapsigargin (10(-8)-10(-6) M) and release experiments in Ca2+-containing or -depleted media showed that influx of Ca2+ into the cells and not acute release from intracellular stores plays an important role in bombesin-stimulated gastrin release. Inhibition of PKC by the specific inhibitor GF 109 203X did not affect bombesin-stimulated release. Rho, a small GTP-binding protein that regulates the actin cytoskeleton, is specifically antagonized by Clostridium botulinum C3 exoenzyme. C3 (10 microg/ml) enhanced basal and bombesin-stimulated gastrin release by 315 and 266%, respectively. The importance of the cytoskeleton for regulation of gastrin release was emphasized by a more pronounced release of gastrin when the organization of the actin cytoskeleton was disrupted by cytochalasin D (5 x 10(-)7 and 10(-)6 M). Wortmannin, a potent inhibitor of phosphoinositide-3-kinase, did not alter bombesin-stimulated gastrin release. Thus, it is concluded that bombesin-induced gastrin release from canine G cells is stimulated by Ca2+ but not by PKC, and is enhanced by disruption of rho/cytoskeletal pathways.
Contraindications to Metformin Therapy in Patients With NIDDM
Authors: Thomas V Sulkin, Deborah Bosman, Andrew J Krentz
Journal: Diabetes Care (1997)

OBJECTIVE Treatment with metformin is occasionally associated with the development of severe lactic acidosis. However, this is usually observed in patients with major contraindications to the drug. In this study, we aimed to determine the prevalence of conditions currently regarded as either contraindications or cautions to the use of metformin in patients with NIDDM. RESEARCH DESIGN AND METHODS The case notes of metformin-treated NIDDM patients (mean age 62 years) attending a United Kingdom university hospital diabetes clinic over a 3-month period were reviewed according to criteria reflecting a pragmatic view of current prescribing recommendations. RESULTS Of 89 consecutive patients whose notes could be evaluated in detail, only 41 (46%) had no contraindications or cautions to metformin whatsoever. Concomitant chronic disorders associated with a potentially increased risk of hyperlactatemia were renal impairment (n = 2; plasma creatinine concentrations 1.7 and 2.3 mg/dl, respectively), cardiac failure (n = 2), and chronic liver disease (n = 2). Other potentially relevant disorders included ischemic heart disease (n = 20), clinical proteinuria (n = 14), peripheral vascular disease (n = 22), and pulmonary disease (n = 7). Multiple conditions (i.e., two, three, or four) were present in eight, five, and one patient(s), respectively. CONCLUSIONS More than half the patients in our series had concomitant conditions or complications conventionally regarded as cautions or contraindications to metformin; ∼ 10% had a multiplicity of such conditions. Regular surveillance is necessary to detect the development of complications such as renal impairment. Vigilance is also required in view of the increased risk of major intercurrent illnesses, which may independently disturb lactate metabolism in patients with NIDDM. Metformin should be withdrawn promptly under such circumstances.
THE UNITED STATES PHARMACOPEIAL CONVENTION
Authors: Arthur D. Hirschfelder
Journal: JAMA (1930)

<h3>To the Editor.</h3> —I was much interested in your editorial regarding the Pharmacopeial convention. I think you were quite right in making it "hot" but it seems to me that your wrath was directed in the wrong place. "The fault, dear Brutus, lies not in our stars but in ourselves." You will recall that every medical school should be officially represented at the Pharmacopeial convention by three representatives, and that the medical schools are ex officio members of the convention. A few of, but by no means all, the medical schools of the country had one representative, but I know of none that were represented by more. As a matter of fact, some of the medical schools, although they appointed three delegates, did not pay the expenses of any. The schools of pharmacy were somewhat better represented. The representation of the state medical societies was much worse. Only a few
Severe Respiratory Depression
Authors: William F. Miller
Journal: JAMA (1962)

Respiratory depression and alveolar hypoventilation require establishment of an airway and mechanically assisted ventilation. A selective respiratory stimulant, vanillic acid diethylamide, produced effective increases of ventilation in 95 of 119 patients with various types of hypoventilatory states. The depth of respiration was increased. The rate was increased also, but to a lesser extent. Prolonged respiratory stimulation was achieved by continuous intravenous therapy in cases of acute depression and by oral administration in convalescent or chronic hypoventilatory states, particularly where aggravated by sleep or by oxygen therapy. This agent was found to be a most valuable adjunct to the management of the patient with severe chronic pulmonary disease and depressed respiration. Side effects were minimal with a wide margin of therapeutic safety demonstrated.
Radiation Therapy for Age-Related Macular Degeneration
Authors: Usha Chakravarthy
Journal: JAMA (1997)

<h3>To the Editor.</h3> —I read with dismay the Medical News &amp; Perspectives article on radiation therapy for wet-type macular degeneration by Mr Skolnick.<sup>1</sup> First, the article showed a complete disregard for the first comprehensively documented phase 1 and 2 trials carried out on this subject. This work initially was reported in 1990,<sup>2</sup>and the long-term follow-up on the same patient group was published in 1996.<sup>3</sup> Second, the claims of visual stabilization and improvement in patients with wet, age-related macular degeneration following external beam radiation therapy (EBRT) as reported by Skolnick are meaningless as they are based entirely on short-term data with no attempt to distinguish between the classic and occult forms of this disease. My own data searches have revealed that since our initial report<sup>2</sup>more than 850 patients have been treated with EBRT worldwide. The baseline visual characteristics of these patients vary markedly within and between centers, with
Nitric oxide cell signaling: S-nitrosation of Ras superfamily GTPases
Authors: K RAINES, M BONINI, S CAMPBELL
Journal: Cardiovascular Research (2007)

The Ras superfamily of small GTPases cycle between inactive GDP-bound and active GTP-bound states to modulate a diverse array of processes involved in cellular growth control. While the basic mechanisms by which GTPase regulatory proteins regulate GTPase substrates have been revealed through numerous studies, detailed studies into the mechanism(s) of free radical-mediated GTPase regulation have only more recently been tackled. This article reviews the mechanism of free radical-mediated GTPase regulation and shows nitric oxide can serve as important regulator of small GTPase proteins (i.e. Ras and RhoA) through protein modifications such as S-nitrosation.
The growing impact of HIV infection on the epidemiology of tuberculosis in England and Wales: 1999 2003
Authors: A. B Ahmed, I. Abubakar, V. Delpech, M. Lipman, D. Boccia, J. Forde, D. Antoine, J. M Watson
Journal: Thorax (2007)

<b>Background:</b> Previous studies have estimated the prevalence of tuberculosis and HIV infection in population subgroups in the UK. This study was undertaken to describe recent trends in the proportion of individuals with HIV infection among reported cases of tuberculosis in England and Wales, and to review the implications for clinical and public health care. <b>Methods:</b> A population-based matching study using national surveillance databases was used to investigate all persons aged 15 years and over reported with a diagnosis of tuberculosis to the Health Protection Agency in England and Wales in 1999–2003. Record linkage was used to match the national tuberculosis and HIV/AIDS surveillance databases to identify all cases of tuberculosis and determine the proportion of patients with tuberculosis co-infected with HIV. The distribution and characteristics of the cases were determined and the trend examined by year. <b>Results:</b> Of 30 670 cases of tuberculosis reported in England and Wales between 1999 and 2003, an estimated 1743 (5.7%) were co-infected with HIV. There was a year on year increase in the proportion from 3.1% (169/5388) in 1999 to 8.3% (548/6584) in 2003 (p for trend &lt;0.0001). Co-infected patients contributed to almost a third of the increase in the number of cases of tuberculosis during the 5 year period. Patients co-infected with HIV were predominantly those born abroad. 18.5% (n = 323) of co-infected patients had not been reported as active cases of tuberculosis on the national tuberculosis database. <b>Conclusion:</b> The proportion of patients with tuberculosis co-infected with HIV in England and Wales is increasing, with the greatest impact on those born abroad regardless of their ethnic origin. With HIV infection contributing substantially to the increase in the number of cases of tuberculosis, close cooperation in the clinical management and accurate notification of patients is vital if appropriate care and public health action is to be achieved.