tbuckley/cabot-search huggingface dataset:
Junctional Cleft [Ca <sup>2+</sup> ] <sub>i</sub> Measurements Using Novel Cleft-Targeted Ca <sup>2+</sup> Sensors
Authors: Sanda Despa, Bo Shui, Julie Bossuyt, Di Lang, Michael I. Kotlikoff, Donald M. Bers
Journal: Circulation Research (2014)

Intracellular Ca(2+) concentration ([Ca(2+)]i) is regulated and signals differently in various subcellular microdomains, which greatly enhances its second messenger versatility. In the heart, sarcoplasmic reticulum Ca(2+) release and signaling are controlled by local [Ca(2+)]i in the junctional cleft ([Ca(2+)]Cleft), the small space between sarcolemma and junctional sarcoplasmic reticulum. However, methods to measure [Ca(2+)]Cleft directly are needed.To construct novel sensors that allow direct measurement of [Ca(2+)]Cleft.We constructed cleft-targeted [Ca(2+)] sensors by fusing Ca(2+)-sensor GCaMP2.2 and a new lower Ca(2+)-affinity variant GCaMP2.2Low to FKBP12.6, which binds with high affinity and selectivity to ryanodine receptors. The fluorescence pattern, affinity for ryanodine receptors, and competition by untagged FKBP12.6 demonstrated that FKBP12.6-tagged sensors are positioned to measure local [Ca(2+)]Cleft in adult rat myocytes. Using GCaMP2.2Low-FKBP12.6, we showed that [Ca(2+)]Cleft reaches higher levels with faster kinetics than global [Ca(2+)]i during excitation-contraction coupling. Diastolic sarcoplasmic reticulum Ca(2+) leak or sarcolemmal Ca(2+) entry may raise local [Ca(2+)]Cleft above bulk cytosolic [Ca(2+)]i ([Ca(2+)]Bulk), an effect that may contribute to triggered arrhythmias and even transcriptional regulation. We measured this diastolic standing [Ca(2+)]Cleft-[Ca(2+)]Bulk gradient with GCaMP2.2-FKBP12.6 versus GCaMP2.2, using [Ca(2+)] measured without gradients as a reference point. This diastolic difference ([Ca(2+)]Cleft=194 nmol/L versus [Ca(2+)]Bulk=100 nmol/L) is dictated mainly by the sarcoplasmic reticulum Ca(2+) leak rather than sarcolemmal Ca(2+) flux.We have developed junctional cleft-targeted sensors to measure [Ca(2+)]Cleft versus [Ca(2+)]Bulk and demonstrated dynamic differences during electric excitation and a standing diastolic [Ca(2+)]i gradient, which could influence local Ca(2+)-dependent signaling within the junctional cleft.
The Relation of Haemorrhages to Unhealthy Surroundings
Authors: J. Meredith
Journal: BMJ (1889)

administered, assuming, or course, that the patient's general health is good.None ofthem will induce abortion, but neither will any of them have any direct effect either in inducing or retarding the menstrual flow, and perfect general health is not incompatible with even the prolonged suppression of menstruation.
332 ILLEGITIMATE ACTIVATION OF BETA-CATENIN SIGNALING PROMOTES PROLIFERATION IN TELOMERASE-IMMORTALIZED HUMAN HEPATOCYTES WITHOUT INDUCTION OF MALIGNANT TRANSFORMATION
Authors: D. Heim, A.W. Lohse, J. Petersen, T.H. Bruemmendorf, H. Wege
Journal: Journal of Hepatology (2008)
A whistleblower's tale
Authors: T. Dalrymple
Journal: BMJ (2012)

Parents are inclined to believe that a child’s failure in exams condemns him or her to a life of poverty and frustration. They might console themselves with the case of Henrik Ibsen (1828-1906), the great Norwegian playwright. He took the entrance exams to medical school while working as an apothecary’s apprentice—but failed them. Would we have heard of him had he passed? This is the very question that is often asked of Hitler and the Viennese art academy.

Ibsen retained his interest in medicine throughout his life, however. A doctor, Thomas Stockmann, is the protagonist of the drama An Enemy of the People . Written in 1882, it is based in part on …
Isopropyl alcohol intoxication. Report of a case associated with myopathy renal failure, and hemolytic anemia
Authors: L. Juncos
Journal: JAMA (1968)

Transient acute renal failure, hemolysis, and myopathy occurred during an episode of isopropyl alcohol intoxication. Whether these three phenomena represent a direct toxic effect of isopropyl alcohol ingestion remains a matter of conjecture. Only further observations of other cases of isopropyl alcohol poisoning will establish the significance of the features described. Despite the similarities of intoxication with isopropyl alcohol to that with ethyl alcohol, there are certain clinical features which may be of value in differentiating the two.
TRANSFER OF RESPONSIVENESS TO HAPTEN CONJUGATES OF POLY-<scp>L</scp>-LYSINE AND OF A COPOLYMER OF <scp>L</scp>-GLUTAMIC ACID AND <scp>L</scp>-LYSINE TO LETHALLY IRRADIATED NON-RESPONDER GUINEA PIGS BY BONE MARROW OR LYMPH NODE AND SPLEEN CELLS FROM RESPONDER GUINEA PIGS
Authors: John Foerster, Ira Green, Jean-Pierre Lamelin, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1969)

Hartley guinea pigs genetically unresponsive to hapten-PLL (poly-L-lysine) conjugates were lethally irradiated and given allogeneic bone marrow from Hartley responder animals. Many of the animals died of graft versus host disease before their response to 2,4-dinitrophenyl-PLL (DNP-PLL) could be measured. The immune response of the surviving recipient animals was evaluated by anti-DNP antibody production, development of delayed hypersensitivity to DNP-poly-L-lysine, as well as by lymph node cell stimulation in vitro by this antigen. 12 of 14 recipient animals thus treated made an immune response as measured by 2 of the 3 parameters. Strain 13 guinea pigs, genetically unable to respond immunologically to DNP-PLL and to DNP-GL (2,4-dinitrophenyl-L-glutamic acid L-lysine copolymer) were lethally irradiated and given bone marrow from (2 x 13) F(1) responder animals or strain 13 bone marrow and (2 x 13) F(1) lymph node and spleen cells. A high proportion of the animals survived this procedure; no evidence of graft versus host disease was observed. Three of three strain 13 animals irradiated and, given strain 13 bone marrow and (2 x 13) F(1) lymph node and spleen, and then immunized with DNP-PL, made a specific immune response. 7 of 10 irradiated strain 13 animals given strain 13 bone marrow and (2 x 13) F(1) lymph node and spleen made an immune response to DNP-GL. However, only one of six irradiated strain 13 animals made a vigorous immune response to DNP-GL after reconstitution with (2 x 13) F(1) bone marrow alone. The ability to transfer the immune response to PLL antigens from responder to nonresponder animals demonstrates unequivocally that the defect in the non-responder animals is immunological rather than due to some other type of non-immunological mechanism. The bone marrow contains all the immunological cells necessary for the expression of the PLL gene. However, the finding that (2 x 13) F(1) lymph node and spleen cells were more effective than (2 x 13)F(1) bone marrow cell populations (known to be a rich source of monocyte precursors) suggests that the cells in which the PLL gene function is expressed may be lymphocytes rather than monocytes and macrophages.
Response of severe systemic mastocytosis to interferon alpha
Authors: None Butterfield
Journal: British Journal of Dermatology (1998)

Six patients with documented systemic mast cell disease were enrolled in a 1-year, phase I study to determine the possible benefits of interferon alpha-2b (IFN-α). IFN-α therapy was begun at a dosage of 0.5 million units/day (MU/day) by subcutaneous injection and increased, as tolerated, to 3.0 MU/day. Subsequent dose modifications were made based on clinical tolerance and response. No immediate, adverse reactions to IFN-α occurred. Several patients showed symptomatic improvement. In two patients ascites resolved and did not recur. Two other patients reported improved energy levels and had decreased size of retroperitoneal, mesenteric and retrocrural nodes. One patient failed to benefit and died shortly after completing 12 months of therapy. Bone marrow mastocytosis decreased by 5% to 10% after 12 months of therapy with IFN-α. Although five of the six patients had a decrease in the urinary excretion of 1-methyl-4-imidazole acetic acid, serum tryptase values did not appreciably change in any patient. Side-effects from IFN-α included hypothyroidism, thrombocytopenia and depression. It is concluded that although treatment with IFN-α was associated with a decline in bone marrow mastocytosis and reduced excretion of histamine metabolites, prolonged therapy may be needed and dose-limiting side-effects are frequent.
Biopsy of Enlarged, Superficial Lymph Nodes
Authors: Stephen Sinclair
Journal: JAMA (1974)

All lymph node biopsies for enlarged, superficial lymph nodes that were performed in a general hospital over a two-year period were reviewed. Biopsies performed in patients with diagnosed malignant neoplasms or systemic illness, or to evaluate an abnormal chest x-ray film were excluded. In 63% of the cases the biopsy led to a specific diagnosis. One quarter of the patients with nondiagnostic lymph node biopsy specimens developed a disease related to the indication for biopsy, usually lymphoma. With the exception of one case, the diagnosis of lymphoproliferative disorder became evident within eight months of the original lymph node biopsy. There should be little hesitation to repeat a nondiagnostic biopsy, especially if systemic symptoms or nonlocalized adenopathy are present. (<i>JAMA</i>228:602-603, 1974)
Hemodynamically significant primary anomalies of the coronary arteries. Angiographic aspects.
Authors: D C Levin, K E Fellows, H L Abrams
Journal: Circulation (1978)

Hemodynamically significant primary anomalies of the coronary arteries are those which alter myocardial perfusion. There are four major types: coronary artery fistulae, origin of the left coronary artery from the pulmonary artery, congenital coronary stenosis or atresia, and origin of the left coronary artery from the right sinus of Valsalva, with subsequent passage of the vessel between the aorta and right ventricular infundibulum. The angiographic features of these lesions are discussed.
Monoclonal antibodies: production and use.
Authors: A M McGregor
Journal: BMJ (1981)

Monoclonal antibodies: production and useOnce or twice in each generation a discovery or innovation excites interest across the whole range of medical science, and monoclonal antibodies come into this class.The theoretical basis for their development came from Burnet's theory' of clonal selection, which predicted that one plasma cell would produce only one immunoglobulin.Studies of myeloma proteins from patients and from animals with various lympho- proliferative disorders affecting B cells have shown that these paraproteins are monoclonal-they are, indeed, derived from a single cell.But while these research studies advanced our understanding of immunoglobulins2 their limitation was that the antigens concerned usually remained unknown.The concept of monoclonal antibodies took on its current dimensions with the work of Milstein and his colleagues3 at the Medical Research Council laboratory of molecular biology in Cambridge.They showed how to produce immortal hybrid myelomas (hybridomas) that secrete monoclonal immuno- globulin molecules of known antibody activity-that is, immunoglobulin molecules that are raised to a specific antigen.Hybridomas are formed by fusing together two different cells in such a way that the hybrid cell that results survives whereas the non-fused parent cell populations do not.antibodies to specific cell surface antigens of both normal'7
Variant 1 of KIAA0101, overexpressed in hepatocellular carcinoma, prevents doxorubicin-induced apoptosis by inhibiting p53 activation
Authors: Lijuan Liu, Xiaobei Chen, Shuixiang Xie, Chuanjie Zhang, Zhenpeng Qiu, Fan Zhu
Journal: Hepatology (2012)

KIAA0101 overexpression was detected in numerous malignant solid tumors and involved in tumor progression; however, the correlation between KIAA0101 expression level and human hepatocellular carcinoma (HCC) was controversial. Our data revealed abnormal expression of the KIAA0101 transcript variant 1 (KIAA0101 tv1) at both messenger RNA and protein levels in HCC tissues and cell lines assessed by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), virtual northern blot, western blot, and immunohistochemical analysis, especially in stage 3-4 HCCs. NIH3T3 cells transfected with KIAA0101 tv1 induced colony formation in vitro and tumor xenorafts in vivo, implying the oncogenic potential of KIAA0101 tv1. Semiquantitative RT-PCR, real-time quantitative RT-PCR, and western blot analysis demonstrated that doxorubicin (Adriamycin, ADR) treatment down-regulated expression of the KIAA0101 tv1, whereas it increased the acetylation of the p53 protein. Additionally, KIAA0101 tv1 prevented cells from apoptosis caused by ADR through suppressing the acetylation of p53 at Lys382. Immunoprecipitation analysis and mammalian two-hybrid assay indicated that KIAA0101 tv1 bound to the transactivation region (1-42 amino acids) of p53 and strongly inhibits its transcriptional activity. Taken together, our data suggest that KIAA0101 tv1 played an important role in the late stage of metastatic HCC and prevented apoptosis after chemotherapeutic drug treatment through inhibiting the transcriptional activity of the p53 gene.KIAA0101 tv1 may function as a regulator, promoting cell survival in HCC through regulating the function of p53. Suppression of the KIAA0101 tv1 function is likely to be a promising strategy to develop novel cancer therapeutic drugs.
Angiotensin converting enzyme and endotoxin induced lung damage in the mouse.
Authors: W O Cookson, M S Wiseman, D J Shale
Journal: Thorax (1985)

Acute pulmonary oedema can be induced by intraperitoneal injection of Escherichia coli endotoxin in the mouse. A fall in serum angiotensin converting enzyme activity is found in mice given endotoxin and in patients with septic adult respiratory distress syndrome, and has been proposed as an indicator of lung microvascular injury. Protein concentration and angiotensin converting enzyme activity in serum, lung, and bronchoalveolar lavage fluid were determined in male mice up to eight hours after injection of endotoxin. By six hours the serum protein concentration had increased and the bronchoalveolar lavage fluid protein concentration had fallen, suggesting fluid shift into the lung. Angiotensin converting enzyme activity fell in serum and lung but increased in bronchoalveolar lavage fluid. As these changes in enzyme activity were not paralleled by changes in protein concentration they are unlikely to be a result of fluid shift or protein leak, and may indicate an active role of the enzyme in the response to sepsis.
Costimulatory Protein 4IgB7H3 Drives the Malignant Phenotype of Glioblastoma by Mediating Immune Escape and Invasiveness
Authors: Dieter Lemke, Philipp-Niclas Pfenning, Felix Sahm, Ann-Catherine Klein, Tore Kempf, Uwe Warnken, Martina Schnölzer, Ruxandra Tudoran, Michael Weller, Michael Platten, Wolfgang Wick
Journal: Clinical Cancer Research (2011)

Recent work points out a role of B7H3, a member of the B7-family of costimulatory proteins, in conveying immunosuppression and enforced invasiveness in a variety of tumor entities. Glioblastoma is armed with effective immunosuppressive properties resulting in an impaired recognition and ineffective attack of tumor cells by the immune system. In addition, extensive and diffuse invasion of tumor cells into the surrounding brain tissue limits the efficacy of local therapies. Here, 4IgB7H3 is assessed as diagnostic and therapeutic target for glioblastoma.To characterize B7H3 in glioblastoma, we conduct analyses not only in glioma cell lines and glioma-initiating cells but also in human glioma tissue specimens.B7H3 expression by tumor and endothelial cells correlates with the grade of malignancy in gliomas and with poor survival. Both soluble 4IgB7H3 in the supernatant of glioma cells and cell-bound 4IgB7H3 are functional and suppress natural killer cell-mediated tumor cell lysis. Gene silencing showed that membrane and soluble 4IgB7H3 convey a proinvasive phenotype in glioma cells and glioma-initiating cells in vitro. These proinvasive and immunosuppressive properties were confirmed in vivo by xenografted 4IgB7H3 gene silenced glioma-initiating cells, which invaded significantly less into the surrounding brain tissue in an orthotopic model and by subcutaneously injected LN-229 cells, which were more susceptible to natural killer cell-mediated cytotoxicity than unsilenced control cells.Because of its immunosuppressive and proinvasive function, 4IgB7H3 may serve as a therapeutic target in the treatment of glioblastoma.
813-2 Incremental value of redox pattern in predicting cardiac allograft vasculopathy after heart transplantation
Authors: Oberdan Parodi, Benedetta De Chiara, Fabio Turazza, Jonica Campolo, Andrea Garascia, Riccardo Bigi, Maria Frigerio, Silvio Klugmann
Journal: Journal of the American College of Cardiology (2004)
Sources of Variation and Bias in Studies of Diagnostic Accuracy
Authors: Penny Whiting, Anne W.S. Rutjes, Johannes B. Reitsma, Afina S. Glas, Patrick M.M. Bossuyt, Jos Kleijnen
Journal: Annals of Internal Medicine (2004)

Background: Studies of diagnostic accuracy are subject to different sources of bias and variation than studies that evaluate the effectiveness of an intervention. Little is known about the effects of these sources of bias and variation. Purpose: To summarize the evidence on factors that can lead to bias or variation in the results of diagnostic accuracy studies. Data Sources: MEDLINE, EMBASE, and BIOSIS, and the methodologic databases of the Centre for Reviews and Dissemination and the Cochrane Collaboration. Methodologic experts in diagnostic tests were contacted. Study Selection: Studies that investigated the effects of bias and variation on measures of test performance were eligible for inclusion, which was assessed by one reviewer and checked by a second reviewer. Discrepancies were resolved through discussion. Data Extraction: Data extraction was conducted by one reviewer and checked by a second reviewer. Data Synthesis: The best-documented effects of bias and variation were found for demographic features, disease prevalence and severity, partial verification bias, clinical review bias, and observer and instrument variation. For other sources, such as distorted selection of participants, absent or inappropriate reference standard, differential verification bias, and review bias, the amount of evidence was limited. Evidence was lacking for other features, including incorporation bias, treatment paradox, arbitrary choice of threshold value, and dropouts. Conclusions: Many issues in the design and conduct of diagnostic accuracy studies can lead to bias or variation; however, the empirical evidence about the size and effect of these issues is limited.
Comparison of an expert system with other clinical scores for the evaluation of severity of asthma
Authors: V Gautier, H Redier, JL Pujol, J Bousquet, H Proudhon, C Michel, JP Daures, FB Michel, P Godard
Journal: European Respiratory Journal (1996)

"Asthmaexpert" was produced at the special request of several clinicians in order to obtain a better understanding of the medical decisions taken by clinical experts in the management of asthmatic patients. In order to assess the severity of asthma, a new score called Artificial Intelligence score (AI score), produced by Asthmaexpert, was compared with three other scores (Aas, Hargreave and Brooks). One hundred patients were enrolled prospectively in the study during their first consultation in the out-patient clinic. Distribution of severity level according to the different scores was studied, and the reliability between AI and other scores was evaluated by Kappa and MacNemar tests. Correlations with functional parameters were performed. The AI score assessed higher levels of severity than the other scores (Kappa = 18, 28 and 10% for Aas, Hargreave and Brooks, respectively) with significant MacNemar test in all cases. There was a significant correlation between AI score and forced expiratory volume in one second (FEV1) (r = 0.73). These data indicate that the AI score is a severity score which defines higher levels of severity than the chosen scores. Correlations for functional parameters are good. This score appears easy to use for the first consultation of an asthmatic patient.
HDL Cholesterol Level Predicts Survival in Men After Coronary Artery Bypass Graft Surgery : 20-Year Experience From The Cleveland Clinic Foundation
Authors: J. M. Foody, F. D. Ferdinand, G. L. Pearce, B. W. Lytle, D. M. Cosgrove, D. L. Sprecher
Journal: Circulation (2000)

HDL cholesterol (HDL-C) is an important independent predictor of atherosclerosis, yet the role that HDL-C may play in the prediction of long-term survival after CABG remains unclear. The risk associated with a low HDL-C level in post-CABG men has not been delineated in relation to traditional surgical variables such as the use of arterial conduits, left ventricular function, and extent of disease.We performed a prospective, observational study of 432 men who underwent CABG between 1978 and 1979 in whom preoperative HDL-C values were available. Baseline lipid and lipoprotein values, history of diabetes mellitus and hypertension, left ventricular ejection fraction, extent of disease, and use of internal thoracic arteries were recorded. Hazard ratios (HRs) were determined in the patients with and without a low HDL-C level, which was defined as the lowest HDL-C quartile (HDL-C </=35 mg/dL). After adjustment for age, as well as for baseline metabolic parameters and surgical variables just noted, HDL-C corresponded to both overall (HR 0.40, CI 0.20 to 0.83, P:=0.01) and event-free (HR 0.41, CI 0.24 to 0.70, P:=0.001) survival. Patients with a high HDL-C level (>35 mg/dL) were 50% more likely to survive at 15 years than were patients with low HDL-C level (</=35 mg/dL) (74% versus 57% adjusted survival, respectively; HR 1.72, P:=0.005). In addition, HDL-C showed a strong effect on time-to-event survival such that patients with an HDL-C level of >35 mg/dL were 50% more likely to survive without a subsequent myocardial infarction or revascularization (HR 1.42, P:=0.02).HDL-C is an important predictor of survival in post-CABG patients. In this study of >8500 patient-years of follow-up, HDL-C was the most important metabolic predictor of post-CABG survival. One third fewer patients survive at 15 years if their HDL-C levels are </=35 mg/dL at the time of CABG. The measurement of HDL-C provides a compelling strategy for the identification of high-risk subsets of patients who undergo CABG.
Suppurative coxitis due to Salmonella typhimurium in systemic lupus erythematosus.
Authors: K Shiota, F Miki, Y Kanayama, M Kohno, A Ohe, K Takamatsu, T Inoue
Journal: Annals of the Rheumatic Diseases (1981)

A 36-year-old woman with systemic lupus erythematosus (SLE) developed septicaemia and subsequently suppurative coxitis due to Salmonella typhimurium. Although systemic treatment with antibiotics eradicated salmonella from the arterial blood, cup arthroplasty and irrigation of the operative wounds with effective antibiotics were needed for eradication of the organism from the affected joints.
B-lymphocyte stimulator (BLyS) stimulates immunoglobulin production and malignant B-cell growth in Waldenström macroglobulinemia
Authors: Sherine F. Elsawa, Anne J. Novak, Deanna M. Grote, Steven C. Ziesmer, Thomas E. Witzig, Robert A. Kyle, Stacey R. Dillon, Brandon Harder, Jane A. Gross, Stephen M. Ansell
Journal: Blood (2005)