tbuckley/cabot-search huggingface dataset:
Characteristics of sarcomere shortening in single frog atrial cardiac cells during lightly loaded contractions.
Authors: M Tarr, J W Trank, P Leiffer
Journal: Circulation Research (1981)

We studied sarcomere performance in single isolated intact cardiac cells using techniques that allow direct measurement of sarcomere length and force. This investigation dealt primarily with sarcomere performance during twitch contractions under lightly loaded conditions. In such contractions, there was a significant portion of the contraction in which sarcomere shortening occurred at constant velocity over a significant range of sarcomere lengths. The constant velocity phase of shortening was followed by a phase of shortening in which sarcomere velocity decreased markedly. Both the velocity and extent of sarcomere shortening depended on the stimulus parameters used to excite the cell. With threshold stimulation, sarcomere velocities during the constant velocity phase of shortening ranged from 1 to 5.5 micron/sec in different cells and significant slowing of sarcomere shortening began at sarcomere lengths of 1.8-2.0 micron. In contrast, when cells were stimulated with a long duration stimulus (200 msec) of large current strength, sarcomere velocities during the constant velocity phase ranged from 6 to 12 micron/sec, and significant slowing did not occur until a sarcomere length of about 1.6 micron was reached. The threshold stimulus strength-stimulus duration relationship was determined on the single cell, and it was found to be of the type expected for a cell having an intact excitable membrane capable of generating an action potential when depolarized to a fixed voltage threshold. The data presented in this paper give direct evidence that the lightly loaded cardiac sarcomere has a velocity of shortening which depends on the level of contractile activation but is independent of sarcomere length at sarcomere lengths greater than about 1.6 micron.
Hemoglobin debrousse (β96[FG3]Leu → Pro): A new unstable hemoglobin with twofold increased oxygen affinity
Authors: Philippe Lacan, Jean Kister, Alain Francina, Gérard Souillet, Frédéric Galactéros, Jean Delaunay, Henri Wajcman
Journal: American Journal of Hematology (1996)

Hemoglobin Debrousse (beta 96[FG3]Leu-->Pro) is a new unstable variant, with high oxygen affinity responsible, in the steady state, for an apparently well-compensated chronic hemolytic anemia. The functional properties of this variant are due to the replacement of a leucine residue which is involved in the hydrophobic environment of the proximal side of the heme. This electrophoretically neutral hemoglobin was found as a de novo case in a 6-year-old girl suffering from severe anemia with hemolysis and transient aplastic crisis, following infection by parvovirus B19.
THE FREQUENCY OF APOPLEXY AMONG THE HIGHER CLASSES WITH SUGGESTIONS FOR ITS PREVENTION AND ESCAPE FROM FATALITY.
Authors: ELMER LEE
Journal: JAMA (1898)

It is rare that an animal dies of apoplexy, but man's days are frequently ended by this disease, coming upon him generally later than the age of 50. The contrast between the simple life of the animal and the complex one of the man is in favor of the former, so far as it relates to health. At the beginning, the young animal and the child are on the same natural footing, both are natures sweet and innocent children. Little by little the child grows away from dependence upon natural methods for its guide, substituting the artificial as life advances and ever becomes more complex. But the animal pursues an even tenor of regularity and simplicity, avoids the excesses and escapes the sad consequences of sickness, pain and premature death. The beginning of disease is at that moment when the laws of health are first violated, and starts with infancy
UK fertilisation authority launches consultation on mitochondrial replacement techniques
Authors: T. Pitts-Tucker
Journal: BMJ (2012)

The UK Human Fertilisation and Embryology Authority (HFEA) has launched a public consultation on the ethical and social implications of new in vitro fertilisation (IVF) techniques designed to avoid the maternal transmission of mitochondrial disease.

Mitochondrial disease affects around one in 200 births each year in the United Kingdom, the HFEA says, and can affect a number of different organs with varying severity.

Two new techniques, maternal spindle transfer and pro-nuclear transfer, could enable women to avoid passing these diseases on to their offspring. Both use a donor’s mitochondria to create a healthy embryo that would then be used in normal IVF treatment. Offspring would thereby share DNA with three people and have an altered germ line such …
A Model to Predict Survival in Patients With End–Stage Liver Disease
Authors: Patrick S. Kamath, Russell H. Wiesner, Michael Malinchoc, Walter Kremers, Terry M. Therneau, Catherine L. Kosberg, Gennaro D'Amico, Rolland E. Dickson, Ray W. Kim
Journal: Hepatology (2001)

A recent mandate emphasizes severity of liver disease to determine priorities in allocating organs for liver transplantation and necessitates a disease severity index based on generalizable, verifiable, and easily obtained variables. The aim of the study was to examine the generalizability of a model previously created to estimate survival of patients undergoing the transjugular intrahepatic portosystemic shunt (TIPS) procedure in patient groups with a broader range of disease severity and etiology. The Model for End–Stage Liver Disease (MELD) consists of serum bilirubin and creatinine levels, International Normalized Ratio (INR) for prothrombin time, and etiology of liver disease. The model's validity was tested in 4 independent data sets, including (1) patients hospitalized for hepatic decompensation (referred to as “hospitalized” patients), (2) ambulatory patients with noncholestatic cirrhosis, (3) patients with primary biliary cirrhosis (PBC), and (4) unselected patients from the 1980s with cirrhosis (referred to as “historical” patients). In these patients, the model's ability to classify patients according to their risk of death was examined using the concordance (c)–statistic. The MELD scale performed well in predicting death within 3 months with a c–statistic of (1) 0.87 for hospitalized patients, (2) 0.80 for noncholestatic ambulatory patients, (3) 0.87 for PBC patients, and (4) 0.78 for historical cirrhotic patients. Individual complications of portal hypertension had minimal impact on the model's prediction (range of improvement in c–statistic: &lt;.01 for spontaneous bacterial peritonitis and variceal hemorrhage to ascites: 0.01–0.03). The MELD scale is a reliable measure of mortality risk in patients with end–stage liver disease and suitable for use as a disease severity index to determine organ allocation priorities.
Epidemic Nonmeningitic Lymphocytic-Choriomeningitis-Virus Infection
Authors: Stephen G. Baum, Andrew M. Lewis, Wallace P. Rowe, Robert J. Huebner
Journal: New England Journal of Medicine (1966)

GRIPPE-like illnesses occurring in groups are likely to be attributed to common colds or, if accompanied by moderate or severe prostration, to an epidemic of influenza. This report presents a series of 10 cases of grippe-like illness in a group of laboratory workers in which the virus of lymphocytic choriomeningitis was proved to be the etiologic agent.The virus of lymphocytic choriomeningitis was first suspected as the causative agent of the human outbreak when a hamster colony previously free of this virus was found to have a high proportion of animals with complement-fixing antibodies to it. The virus was introduced . . .
Resistance to imatinib, low-grade FDG-avidity on PET, and acquired KIT exon 17 mutation in gastrointestinal stromal tumour
Authors: Florian Grimpen, Desmond Yip, Grant McArthur, Paul Waring, David Goldstein, Maurice Loughrey, Victoria Beshay, Guan Chong
Journal: The Lancet Oncology (2005)
Once-Daily Fluticasone Furoate Nasal Spray Showed Greater Improvements in Relieving Nighttime Nasal Symptoms and Increasing Peak Nasal Inspiratory Flow Versus Oral Fexofenadine in Subjects With Seasonal Allergic Rhinitis (SAR)
Authors: B MARTIN, C ANDREWS, R JACOBS, D MOHAR, W TOLER, B PRILLAMAN, E PHILPOT
Journal: Journal of Allergy and Clinical Immunology (2008)
Hepatitis C virus infection in living color
Authors: Nicholas S. Eyre, Michael R. Beard
Journal: Hepatology (2010)

Abstract Hepatitis C virus (HCV), which infects 2-3% of the world population, is a causative agent of chronic hepatitis and the leading indication for liver transplantation. The ability to propagate HCV in cell culture (HCVcc) is a relatively recent breakthrough and a key tool in the quest for specific antiviral therapeutics. Monitoring HCV infection in culture generally involves bulk population assays, use of genetically modified viruses and/or terminal processing of potentially precious samples. Here we develop a cell-based fluorescent reporter system that allows sensitive distinction of individual HCV-infected cells in live or fixed samples. We demonstrate use of this technology for several previously intractable applications, including live-cell imaging of viral propagation and host response, as well as visualizing infection of primary hepatocyte cultures. Integration of this reporter with modern image-based analysis methods could open new doors for HCV research.
Reply to M. Fink
Authors: Kristofer Prepelica, Glenn Heller, Howard I. Scher
Journal: Journal of Clinical Oncology (2011)

In the Androgen-Independent Prostate Cancer Study of Calcitriol Enhancing Taxotere-2 (ASCENT-2), Scher et al 1 found no effect of DN-101, a high-concentration formulation of calcitriol, when given in combination with docetaxel for treatment of castration-resistant prostate cancer. 1 This result contradicts the antitumoral effect found with DN-101 in the ASCENT-1 study, 2 which had a different design that may have contributed to the contradictory results.Regarding the toxicity, ASCENT-2 reports a result not mentioned in the discussion, which, however, is supported by ASCENT-1: the rate of febrile neutropenia was 1.0% in the DN-101 arm and was 4.6% in the control arm.This difference, in my opinion, is statistically highly significant (P Ͻ .001with the 2 test).Surprisingly, pneumo- nias showed no difference, with 3.1% in the DN-101 and 2.9% in the control arm. 1 However, in ASCENT-1, the rate of grades 3 to 4 infections under DN-101 was also lower, with eight occurrences with DN-101 and 13 occurrences in the control group. 2 Similarly, in a recent pilot study with 81 patients who had suspected infection, patients with baseline 25-hydroxyvitamin D (25-OHD) levels less than 75 nmol/L (reference value, 50 to 150 nmol/L; optimal value, Ͼ 75 nmol/L) were more likely to have severe sepsis than patients with 25-OHD levels Ն 75 nmol/L (61% v 24%; P ϭ .006).All four patients who died during the index hospitalization had 25-OHD levels less than 75 nmol/L. 3 In theory, these correlations are supported by the proven antibacterial 4 and the highly probable antiviral effects of vitamin D. 5 Recently, I reported on two patients with low initial 25-OHD levels and a marked improvement of chemotherapy-induced adverse effects during vitamin D treatment. 6A challenging aspect concerning adverse effects is undoubtedly the prophylaxis and treatment of leukopenic infections.Therefore, the difference in the rate of febrile neutropenias and infections with and without DN-101, which is not discussed by Scher et al, 1 could be the most relevant result of the ASCENT studies.
Stilbene derivatives that are colchicine site microtubule inhibitors have antileukemic activity and minimal systemic toxicity
Authors: Thai M. Cao, David Durrant, Ashutosh Tripathi, Jihua Liu, Schickwann Tsai, Glen E. Kellogg, Daniele Simoni, Ray M. Lee
Journal: American Journal of Hematology (2008)

Stilbenes are a group of natural compounds with many biological activities. Two highly potent stilbenes, cis-3,4',5-trimethoxy-3'-aminostilbene (stilbene 5c) and cis-3,4',5-trimethoxy-3'-hydroxystilbene (stilbene 6c) induce G2/M cell-cycle arrest and leukemic cell death in nanomolarity range without affecting normal bone marrow progenitor cells. The mechanism of stilbenes is mediated by interfering with microtubule polymerization through the colchicine-binding site. Docking of the stilbenes into tubulin structure confirms that stilbenes fit into the colchicine-binding pocket. Animal studies show that stilbenes are well tolerated in mice and are capable of inducing more than 50% leukemic cell death by a single dose injection. A 5-day treatment with low-dose stilbenes suppresses tumor growth in mice with established tumor xenografts. No major organ damage was detected by histological section. Our results indicate that stilbene 5c is a microtubule-interfering agent and can be potentially useful in leukemic therapy.
Incidence of serum antibodies to native type I and type II collagens in patients with inflammatory arthritis.
Authors: R B Clague, M J Shaw, P J Holt
Journal: Annals of the Rheumatic Diseases (1980)

Using a new solid-phase double-antibody radioimmunoassay we have determined the incidence of serum IgG antibodies to native bovine type I and type II collagens in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis. Raised serum IgG antibody levels to native type I collagen were present in 49% of patients with RA, 30% with AS, and none of the patients with psoriatic arthritis. Raised serum IgG antibody levels to native type II collagen were present in 42% of patients with RA, 30% with AS, and none of the patients with psoriatic arthritis. In rheumatoid arthritis there was a lack of correlation between IgG antibody levels to collagen and the erythrocyte sedimentation rate, IgG rheumatoid factor, and circulating immune complexes measured by the Clq-binding activity. In ankylosing spondylitis IgG antibody levels to native type II collagen were raised only in patients with peripheral joint involvement. The significance of IgG anticollagen antibodies is not certain, but parallels with rheumatoid factor are discussed.
Changes in ER beta versus ER alpha in short-term studies of antiestrogen therapies.
Authors: G Dzagnidze, JF Robertson, I Ellis, A Green, H Zhang, V Speirs, A Shaaban, S Garnett, J Lindemann
Journal: Cancer Research (2009)

Abstract Abstract #5113 Background: Fulvestrant (Faslodex™) is a novel estrogen receptor (ER) antagonist with no agonist effects used in the treatment of postmenopausal women with advanced breast cancer. Compared with other antiestrogen therapies, fulvestrant has a distinct and different mode of action; on binding to the ER it induces a rapid and dose-dependent degradation of ER alpha and concomitant decreases in progesterone receptor (PgR) levels and Ki67 labeling index (LI). The action of fulvestrant on ER beta is unknown and has been investigated in relation to other biomarkers in this study.&amp;#x2028; Methods: This randomized, multicenter study included postmenopausal patients with previously untreated breast tumors (stage T1-T3) that were either ER+ or ER unknown. Patients were randomized to receive a single intramuscular dose of fulvestrant (50 mg [n=39], 125 mg [n=38], or 250 mg [n=44]), continuous daily tamoxifen (Nolvadex™) (20 mg/day [n=36]), or matching tamoxifen placebo (n=33) for 14–21 days prior to surgery. The effects of antiestrogen therapy on ER beta 1 and ER beta 2 levels and the relationship between these effects and changes in ER alpha, PgR and Ki67 LI were investigated. Effects on ER (alpha and beta) and PgR were determined by immunohistochemistry and expressed as mean percentage change from baseline H-score. Ki67 LI was determined as described previously1 and was expressed as median percentage change from baseline.&amp;#x2028; Results: There was no overall treatment effect following placebo or antiestrogen therapy on ER beta 1 H-score (p=0.8537) or ER beta 2 H-score (p=0.5494). There were no significant differences between the individual fulvestrant dose groups, tamoxifen and placebo for mean changes in either ER beta 1 (50 mg: +34.8%, 125 mg: +42.8%, 250 mg: +15.5%; tamoxifen: +29.8%; placebo: +29.7%) or ER beta 2 (50 mg: +87.9%, 125 mg: +82.9%, 250 mg: +97.4%; tamoxifen: +98.1%; placebo: +64.2%). No correlations were observed between changes in ER beta 1 and changes in ER beta 2, nor between either ER beta 1 or 2 and ER alpha, PgR or Ki67 LI.&amp;#x2028; Conclusion: Changes in ER beta did not correlate with fulvestrant dose (50 mg, 125 mg, or 250 mg) or other variables that have previously been shown to be related to fulvestrant activity. This study does not support the investigation of ER beta 1 or 2 as markers of the biological activity of fulvestrant high dose (500 mg/month) in ongoing trials such as FIRST and CONFIRM.&amp;#x2028; 1Robertson et al. Cancer Res 2001; 61: 6739-6746. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5113.
Occupationally Acquired Vibratory Angioedema with Secondary Carpal Tunnel Syndrome
Authors: MARK H. WENER
Journal: Annals of Internal Medicine (1983)

After several years of occupational exposure to vibration, a man developed episodic vibratory hand swelling, erythema, and pruritus. He subsequently developed symptoms compatible with carpal tunnel syndrome, but his median nerve conduction velocity remained normal. After experimental vibration of the forearm, plasma histamine levels in the ipsilateral antecubital vein rose in association with localized angioedema and slowed median nerve conduction velocity. There was no evidence of other causes of angioedema. Occupational exposure to vibration may predispose to the development of vibratory angioedema, which may predispose to intermittent compression neuropathy.
Cholelithiasis in Young People
Authors: Roger K. Harned
Journal: JAMA (1977)

To the Editor.—  We read with interest the article by Dr Goodman regarding cholelithiasis in persons under 25 years old (236:1731, 1976).  A similar study performed by Babbitt and me yielded basically the same results. 1 We reviewed 367 cases of cholelithiasis in children from the literature and our own experience and found that 81% had no evidence of a hemolytic anemia. The age range was from 3 months to 15 years, with 70% of the patients being female. The pain associated with cholelithiasis in children was most often mistaken for acute appendicitis. Oral cholecystography was diagnostic of cholelithiasis in 70% of the cases. We also found that plain roentgenograms of the abdomen were of more value in children than in adults for establishing the diagnosis of cholelithiasis, since 50% of these children had opaque gallstones visible on plain abdominal films. Dr Goodman's study reinforces our impression that cholelithiasis in
PREDICTION OF CARDIOVASCULAR RISK IN DIABETIC VASCULAR SURGERY REQUIRES QUANTITATIVE DIPYRIDAMOLE THALLIUM SCINTIGRAPHY
Authors: Steven E. Lane, John J. Pippin, Stanley M. Lewis, Edward J. Kosinski, David Campbell, Thomas Hill, Hugh Wheeler
Journal: Clinical Nuclear Medicine (1988)

s of the 20th Annual Meeting of the New England Chapter of the Society of Nuclear Medicine: PDF Only
EDEMA IN MYOCARDIAL INSUFFICIENCY
Authors: Milton B. Cohen
Journal: JAMA (1925)

<h3>To the Editor:</h3> —InThe Journal, November 14, Resnik and Keefer call attention to the edema of the face sometimes seen in grave myocardial insufficiency. They conclude that it is probably due to impaired renal function, and cite studies of the nonprotein content of the blood as evidence for this conclusion. If my understanding of their point of view is correct, they feel that the facial edema is of a different nature than that observed in the dependent portions: that the latter is the result of circulatory deficiency with stasis, and that the former is the result of kidney insufficiency produced by stasis in the kidney. That the finding of increased amounts of nonprotein nitrogen in the blood of persons with severe myocardial failure is not absolute evidence of kidney insufficiency, and that the height of the retention is not an absolute index of the degree of kidney insufficiency is
Reduction of infarct size by oxygen inhalation following acute coronary occlusion.
Authors: P R Maroko, P Radvany, E Braunwald, S L Hale
Journal: Circulation (1975)

This study was carried out in order to determine the effects of the inspiration of O2-enriched air on the size of myocardial infarction. In 15 anesthetized dogs, epicardial electrograms were recorded from 10 to 14 sites on the anterior surface of the left ventricle before and after intermittent occlusion of the left anterior descending coronary artery or one of its major branches. In each dog, one occlusion was carried out while the fraction of inspired oxygen (FIO2) was 0.20 and the other while the FIO2 was 0.40. With an FIO2 of 0.20 the average ST-segment elevation (ST) was 4.0 +/- 0.6 mV (SEM) and the number of sites exhibiting ST-segment elevations exceeding 2 mV (NST) 15 minutes following occlusion was 6.2 +/- 0.7 sites; comparable values following occlusion with an FIO2 of 0.40 were 1.8 +/- 0.4 mV (P less than 0.01) and 2.7 +/- 0.7 sites (P less than 0;01), reflecting reduction in acute myocardial ischemic injury; An FIO2 of 1.0 did not decrease myocardial injury further. In 24 other dogs, occlusion was maintained for 24 hours. In nine dogs in which FIO2 was increased from 0.20 to 0.40 30 minutes after occlusion, myocardial creatine phosphokinase activity (CPK) was less depressed in sites having comparable levels of ST-segment elevation at 15 minutes than in dogs that respired an FIO2 of 0.20 during the entire 24 hours. All (54) sites with ST-segment elevations greater than 3 mV in the 0.20 FIO2 group showed early signs of myocardial infarction, while only 49% of such specimens showed infarction in the 0.40 FIO2 group. Thus it is concluded that 0.40 FIO2 following an experimental coronary artery occusion decreases acute ischemic injury and reduces the eventual development of necrosis, as evaluated by enzymatic and histological techniques.