tbuckley/cabot-search huggingface dataset:
Targeted mutagenesis: analysis of phenotype without germ line transmission.
Authors: A Nagy, J Rossant
Journal: Journal of Clinical Investigation (1996)

The available techniques for directed gene manipulation in the mouse are unprecedented in any multicellular organism and make the mouse an invaluable tool for unraveling all aspects of mammalian biology. To realize fully the potential of these genetic tools requires that phenotypic analysis be efficient, rapid, and complete. Genetic chimeras and mosaics, in which mutant cells are mixed with wild-type cells, can be used to augment standard analysis of intact mutant animals and alleviate the time required and the expense involved in generating and maintaining multiple strains of mutant mice.
Why Do Women Not Use Antenatal Services in Low- and Middle-Income Countries? A Meta-Synthesis of Qualitative Studies
Authors: Kenneth Finlayson, Soo Downe
Journal: PLoS Medicine (2013)

In a synthesis of 21 qualitative studies representing the views of more than 1,230 women from 15 countries, Kenneth Finlayson and Soo Downe examine the reasons why many women in low- and middle-income countries do not receive adequate antenatal care.
PRACTICAL ACCURACY AND CONVENIENCE IN TRIAL LENSES
Authors: EDWARD JACKSON
Journal: JAMA (1930)

In 1878 the sixth section of the American Medical Association, devoted to diseases of the eye, ear, nose and throat, was established and Herman Knapp made chairman. In 1879 the first meeting was held at Atlanta, Ga. From that time to this, the trial case and its use have never been the subject of a paper, or discussion, before this section. There has not been a meeting at which cataract and cataract operations have not figured on the program; glaucoma has almost as frequently claimed attention, and at every session new instruments are shown and discussed. But there has been no discussion of test lenses and the trial case, although every member uses a trial case more frequently than any other part of his armamentarium, and many use trial cases less suited to their actual needs than any operative instrument they would tolerate. In 1891 George M. Gould stated before
ADVERTISING OF RADIUM EMANATION SOLUTION
Authors: L. G. Rowntree
Journal: JAMA (1925)

<h3>To the Editor:</h3> —While attending the meeting of the Congress of Physicians and Surgeons in Washington, I saw some large signs advertising radium water in which my name was utilized as advocating the use of radium. At the Traymore Hotel, in Atlantic City, I was presented with a circular advertisement of the National Radium Products Company, in which they advertised radium water and again used my name as though I advocated its use. My name was used for general advertising purposes without my knowledge or consent. I have been interested in the use of radium in internal medicine for ten or twelve years. In collaboration with Dr. Walter Baetjer, I presented a paper before the Section on Pharmacology and Therapeutics of the American Medical Association in 1913, entitled "Radium Water in Internal Medicine." Our conclusions read as follow: We must state frankly that the results in our small series of
Intra-Aortic Balloon Counterpulsation in Cardiogenic Shock
Authors: Stephen Scheidt, Gary Wilner, Hiltrud Mueller, Donald Summers, Michael Lesch, Gerald Wolff, Joseph Krakauer, Melvyn Rubenfire, Peter Fleming, George Noon, Newland Oldham, Thomas Killip, Adrian Kantrowitz
Journal: New England Journal of Medicine (1973)

Eighty-seven patients with cardiogenic shock were treated with the intra-aortic counterpulsating balloon in 10 institutions according to a common protocol. Clinical and physiologic responses were favorable in most patients. Heart rate fell from 110 ± 24 (mean ± S.D.) to 103 ± 21 beats per minute, systolic arterial pressure ("afterload") fell from 76 ± 22 to 57 ± 17 mm Hg, diastolic arterial pressure increased from 53 ± 12 to 83 ± 19 mm Hg, and mean arterial pressure did not change. Cardiac output increased 500 ml per minute, and a decrease in lactate production or increase in lactate extraction by the myocardium occurred in 18 of 19 patients with metabolic studies. Fifty-two patients died during balloon assistance, and 35 survived; 15 of the survivors left the hospital, and eight have lived for more than one year. Attempts to predict survival in advance, or from response to balloon counterpulsation, were generally unsuccessful, and precise indications for initiation and termination of balloon counterpulsation remain in doubt. (N Engl J Med 288:979–984, 1973)
Extracellular matrix proteins give new life to cell culture
Authors: George R. Martin, Hynda K. Kleinman
Journal: Hepatology (1981)

Under standard culture conditions, hepatocytes fail to proliferate or to maintain liver-specific functions (1, 2).Recent work, such as that reported by Ponce et al. in this issue of Hepatology and in an earlier article (3), suggests that the conditions used in the past to culture hepatocytes and other differentiated cells may be inappropriate or inadequate.This is part of an ongoing revolution in the way cells are cultured.The price of fetal calf serum, the elixir of cell culture, has undergone recent increases of a magnitude to whet the appetite of OPEC.Concomitantly, it has been realized that serum is not the physiological nutrient for all cells.In fact, while some cells grow in calf serum, they will grow and differentiate better when serum is replaced by various defined factors such as steroid hormones and other growth factors, transferrin, and proteins which stimulate cell attachment (4).Under these conditions, for example, neuroblastoma cells proliferate and maintain their cell-specific functions.Further, by eliminating serum, the overgrowth of slowly proliferating cells by fibroblasts may be prevented.Defined media have not yet been well developed for hepatocytes but efforts in this regard are underway (5).The substrate on which cells are grown is also critical for their proliferation and differentiation in culture.Treated plastic or glass dishes which are used routinely for tissue culture were previously thought to provide a charged surface to which the cells could bind by electrostatic forces.More recently, however, it has been shown that cells adhere to substrates by other, more physiological mechanisms as well.It is likely that these surfaces bind specific cell attachment proteins which are made by the cells or are present in serum, and that the cells bind to the adsorbed protein.The detailed reaction is best understood for collagen substrates.Fibroblasts do not bind directly to collagen substrates (6).Rather, a large glycoprotein (M, = 440,000) in serum binds to collagen and subsequently to the cell surface.This glycoprotein was isolated and shown to be identical to the previously
Dose of Non-Heat-Treated Factor VIII Concentrate and HIV-1 RNA Levels-Reply
Authors: Thomas R. O'Brien
Journal: JAMA (1997)

In Reply.  —Dr Montoro and colleagues recategorized our data and used a test for linear trend instead of the more conservative overall Mantel-Haenszel ϰ2test that we used. They point out that subjects who received lower annual doses of non-heat-treated factor VIII concentrate (between 1978 and 1984) had somewhat higher HIV-1 RNA levels. An association between lower factor VIII dose and higher HIV-1 RNA levels would be consistent with a recent report by Montoro et al that lower factor-concentrate dose was associated with faster progression to AIDS in 225 HIV-1-infected Spanish hemophiliac patients.1Therefore, we examined the relationship between factor VIII dose, HIV-1 RNA levels, and time to development of AIDS in our study, the Multicenter Hemophilia Cohort Study (MHCS).  Although only a small subset of MHCS subjects were tested for HIV-1 RNA, data on factor VIII dose and clinical outcome were available for 1094 HIV-1-infected adults and children. As
BIOLOGICAL EXPRESSIONS OF LYMPHOCYTE ACTIVATION
Authors: Robert R. Rich, Carl W. Pierce
Journal: The Journal of Experimental Medicine (1973)

The effects of nonspecific phytomitogens on primary plaque-forming cell (PFC) responses of mouse spleen cells to heterologous erythrocytes in vitro were studied. Spleen cell cultures treated with concanavalin A or phytohemagglutinin in vitro or established with spleen cells derived from mice injected with concanavalin A 24 h previously were similarly affected. In both cases, submitogenic doses resulted in substantial enhancement of PFC responses, whereas 10-fold larger doses were profoundly inhibitory. In contrast to the suppressive effects of mitogenic doses of phytomitogens added at culture initiation, addition of these same doses to cultures 48 h later resulted in increased PFC responses. This enhancement could be observed within 1 h after treatment and consequently could not be ascribed only to mitotic expansion of the antibody-synthesizing clone. Activation of spleen cells with specific antigen before mitogen treatment was not required for expression of the enhancing or suppressing effects on PFC responses. IgM and IgG PFC responses were similarly affected. Studies of cell interactions revealed that as few as 10(5) spleen cells obtained from mice treated with concanavalin A in vivo synergistically enhanced the PFC responses of 10(7) normal spleen cells. This enhancement was mediated by mitogen-activated T lymphocytes which were resistant to 2000 R irradiation 24 h after activation. The relevance of these observations to emerging concepts of helper and suppressor T cell activity is discussed.
P214 Pathological staging of malignant pleural mesothelioma. How important is nodal disease in selection for radical surgery?
Authors: A. Nakas, K. Lau, D. Waller
Journal: Thorax (2010)

<h3>Purpose</h3> Selection criteria for radical surgery in malignant pleural Mesothelioma (MPM) and related clinical trials remain controversial. The relative importance of nodal metastases and the need for preoperative nodal staging are undetermined. <h3>Methods</h3> From a prospective database, we identified 203 patients (175 male and 28 female) with non-sarcomatoid MPM (Epithelioid 154 patients; Biphasic 49 patients). Preoperative staging included CT and mediastinoscopy. We investigated the effect of nodal burden and distribution on overall survival. <h3>Results</h3> 125 patients underwent extrapleural pneumonectomy (EPP) and 78 radical pleurectomy/decortication (RPD) all with systematic nodal dissection. There was no difference in survival between EPP or RPD: 1 year 63% vs 56%; 3 year 17% vs 15% and 5 year 8% vs 5% p=0.55. The median number of lymph nodes resected was 10 (1–58); 88 (43%) patients were N0, 18 (9%) N1 and 97 (48%) N2. Patients with N0 disease had the best prognosis: median survival 22 months (SE 3, 95% CI 16 to 28) versus 11 months (SE 3, 95% CI 4 to 18) for N1 and 14 months (SE 1, 95% CI 11 to 17) for N2, p=0.005. There was no significant survival difference between N1 and N2, p=0.85. Overall survival was associated with the absolute number of positive extrapleural lymph nodes (p=0.05) and the number of extrapleural nodal stations involved (p=0.01) but not, the total (intra and extra pleural) number of involved nodes or stations (p=0.13 and 0.23). <h3>Conclusions</h3> Extrapleural nodal status remains one of the most important prognostic factors following radical surgery for malignant pleural Mesothelioma. These data have important implications for preoperative staging and revision to the current IMIG staging system.
Epitope mapping of human antibody response against HCV/E2 glycoproteinby generation of monoclonal recombinant fabs
Authors: R. Burioni, F. Bugli, C. Di Campli, A. Desogus, A. Manzin, A. Gasbarrini, G. Gasbarrini, G. Fadda
Journal: Journal of Hepatology (2000)
A Clinical Rule To Predict Preserved Left Ventricular Ejection Fraction in Patients after Myocardial Infarction
Authors: Marc T. Silver
Journal: Annals of Internal Medicine (1994)

To derive and validate a clinical prediction rule that identifies patients after myocardial infarction who have preserved left ventricular systolic function.Retrospective analysis of a prospective cohort study, with a derivation set to generate a clinical prediction rule and a validation set to test the prediction rule.Urban tertiary care hospital.314 consecutive patients admitted with myocardial infarction who had one or more of the following tests to determine left ventricular ejection fraction: transthoracic echocardiography, contrast left ventriculography, or radionuclide ventriculography.Left ventricular ejection fractions were determined by transthoracic echocardiography, contrast left ventriculography, and gated blood pool scan.Multivariate analysis of patients in the derivation set yielded the following rule: The left ventricular ejection fraction is predicted to be 40% or more in patients who have 1) an interpretable electrocardiogram, 2) no previous Q-wave myocardial infarction, 3) no history of congestive heart failure, and 4) an index myocardial infarction that is not a Q-wave anterior infarction. In the derivation and the validation sets, the positive predictive value of the prediction rule was more than 0.98.A simple clinical prediction rule using easily obtained historical and electrocardiographic data reliably identifies a substantial percentage of patients after myocardial infarction (40% in our hospital) who are likely to have preserved left ventricular systolic function. If validated in other patient populations, application of this prediction rule in clinical practice could result in a substantial decrease in the cost of treating uncomplicated myocardial infarction.
OBSERVATIONS UPON THE NOGUCHI MODIFICATION OF THE WASSERMANN COMPLEMENT FIXATION TEST IN THE DIAGNOSIS OF LUES IN THE MILITARY SERVICE
Authors: Charles F. Craig
Journal: The Journal of Experimental Medicine (1910)

In the vast majority of cases examined in this laboratory the result of the Wassermann test was simply confirmatory of the clinical findings, but there were numerous suspicious cases, or cases in which symptoms were present and the patient denied a specific history, in which the test was of the greatest value, and it is in such instances, perhaps, that it may be regarded as "the court of last resort " in arriving at a conclusion regarding the nature of the condition present. Certainly if there is any value in experience and statistics, we are justified in regarding this test as the most valuable means we possess of diagnosing lues, and our experience with the Noguchi modification of the test has justified all that has been claimed for that method. We believe that our results have proven that by the use of the complement fixation test in the military service it is possible to prevent the enlistment of men suffering from latent lues who would otherwise be enlisted; to control specific treatment by using it as an index of the efficiency of such treatment; to clear up the diagnosis of obscure or suspicious cases; and to enable the surgeon to avoid mistakes in discharges for disability in cases suspected of this disease. Owing to the facility with which clinical observations can be made in armies, and the control that is possible of tested individuals, it is to be hoped that the Noguchi modification of the complement fixation test will be more widely used than it has been in the military services, for which we believe it is especially adapted. So far as we are aware the Medical Department of our army is the first to adopt this test as a routine diagnostic procedure and to apply it in the case of applicants for enlistment.
Psychodynamics and Therapeutic Aspects of Anorexia nervosa
Authors: H. Becker, P. Körner, A. Stöffler
Journal: Psychotherapy and Psychosomatics (1981)

38 patients who had suffered from anorexia nervosa were examined and followed up in a catamnestic study, and their biography, family dynamics, eliciting situation and history of illness were studied. The investigation was carried out by means of interviews, questionnaires and personality tests. As to biography and family dynamics, our results are partly complementary and partly contradictory to previously published results of other investigations. Our patients received inpatient psychotherapy over an average period of 3 months and were followed up 2–5 years later. The following prognostic criteria proved to be significant: vomiting as part of the symptoms; chronification (psychotherapy delay), and ability to achieve a constructive therapist/patient alliance. Patients whose weight was largely back to normal by the end of therapy, but were still amenorrhoeic, showed unfavourable development in psychosocial relations. The catamnestic results improved with increasing time lapse between the end of therapy and follow-up investigation.
Nephritogenicity of antibodies to proteoglycans of the glomerular basement membrane--I.
Authors: H Makino, J T Gibbons, M K Reddy, Y S Kanwar
Journal: Journal of Clinical Investigation (1986)

We investigated nephritogenic potential of antibodies to heparan sulfate-proteoglycan of glomerular basement membrane. Glomeruli were isolated, basement membranes were prepared, proteoglycans extracted, and purified core protein was obtained. We immunized rabbits with the core protein, IgG fraction prepared from the antisera and specificity of the antibody determined. A single immunoprecipitin line in agar diffusion plate and a single band (approximately 18,000 mol wt) on the immunoblot autoradiograms were visualized. The antibody showed precise reactivity with the glomerular basement membranes. The clearance studies indicated that approximately 75% of the radioiodinated antibody disappeared from circulation within 1 h and 1-2% bound to the kidney. For nephritogenicity experiments, the antibody was intravenously administered into rats and we examined their kidneys at 1 h to 24 d later. A linear immunofluorescence of glomerular basement membranes was observed with rabbit IgG at all times while that of C3 until the 10th day. Early morphologic changes included glomerular infiltration of polymorphonuclear leukocytes with focal exfoliation of endothelium. The leukocytic infiltration subsided by the third day and was followed by progressive thickening of basement membranes, focal mesangial cell proliferation, increase in mesangial matrix, and accumulation of monocytes. Focal knob-like thickening of glomerular basement membrane was observed from the 15th day onward. Regularly-spaced electrondense deposits were seen in the lamina rara interna and externa of glomerular basement membranes and persisted throughout the investigatory period. No significant proteinuria was observed at any stage of the experiment. These findings suggest that the antibodies to the basement membrane heparan sulfate-proteoglycan are nephrotoxic but possess weak nephritogenic potential.
Deepak Srivastava
Authors: Ruth Williams
Journal: Circulation Research (2014)

New Leaders in Cardiovascular ScienceO ne percent of all births worldwide are to children with a heart malformation.To better understand what has gone wrong in these children and how to prevent or correct such malformations in others, Deepak Srivastava, the Younger Family Director at the Gladstone Institute of Cardiovascular Disease and Director of the Roddenberry Stem Cell Center at Gladstone, studies the biology of heart development.He has identified several transcription factors, microRNAs, and other components that are essential for cardiogenesis in the mammalian embryo, 1-5 but Srivastava's work is relevant for heart problems affecting adults too.Heart failure after a heart attack is a major cause of death in men and women, and Srivastava is using the knowledge he gains from studying heart development to coax damaged adult hearts to regenerate.For example, his team has shown that, using a cocktail of developmental factors, heart fibroblasts-cells that form the rigid scar tissue after a myocardial infarction-can be converted into contracting cardiomyocytes both in vitro and in live mice. 6,7 From caring for sick children, Srivastava is a physician at the Benioff Children's Hospital in San Francisco, to regenerating mouse hearts, all of Srivastava's career decisions and research interests have come down to the same basic principle, he told Circulation Research in a recent interview: do what you feel most passionate about, rather than what seems practical.This, he says, is the key to a happy career. Where Did You Grow Up?My parents, Satish and Rani Srivastava, immigrated to the United States from India when I was less than a year old, along with my 2 older sisters.My father was a scientist and he moved to the City of Hope Medical Center in Los Angeles as a faculty member and stayed there for 8 years.So I grew up in Los Angeles for my first 8 years, but then he
Abstract P6-04-16: TGF-b2, a novel target of CD44-promoted breast cancer invasion
Authors: H Al-Riyami, S Madani, I Gupta, S Shanmuganathan, ME Abdraboh, Y Al-Farsi, MHG Raj, A Ouhtit
Journal: Cancer Research (2013)

Abstract Hyaluronan (HA) mediates communication between cancer cells and the environment via interactions with the cell surface receptor CD44. We have previously shown that CD44-HA interaction in BC cells promotes adhesion to bone marrow endothelial cells. This suggests that HA/CD44 signalling may be correlated with breast cancer (BC) metastasis. The long-term objective of this study is to increase our understanding of the mechanisms by which CD44-HA interaction promotes BC metastasis, and further identify and validate CD44-downstream transcriptional targets for anti-metastatic therapy. Pursuant to this goal, we have developed a tetracycline (tet)-regulated expression of CD44 gene in the BC cell line MCF-7 (B5 clone) and identified TGF-beta2 (Transforming Growth Factor beta-2; 3 fold induction) as a potential CD44s-downstream transcriptional target by microarray analysis. To further validate this finding, the same RNA samples, used for microarray analysis and their corresponding protein lysates collected from the BC cell line MCF-7-B5, were examined for CD44 expression in the presence of HA for 18, 24, and 48 hr post-tet withdrawal. Expression of TGF-beta 2 was examined using RT-PCR and western-Blot analyses. Our results showed that TGF-beta2 mRNA levels were significantly elevated following the removal of tet at 18, 24, and 48 h post-HA stimulation compared to the parental cells. Furthermore, the TGF-beta2 precursor protein increased in a time-dependent pattern upon HA-stimulation and in the absence of tet. More interestingly, inhibition of CD44 gene by RNAi method decreased TGF-beta2 expression upon HA-stimulation and in the absence of tet. Our data strongly support the hypothesis that TGF-beta2 is a potential target of HA/CD44- downstream-signaling mediating BC cell invasion. Ongoing investigation aims to elucidate the signal transduction pathways coupling CD44 to the regulation of TGF-beta2 expression, and further validate CD44/TGF-beta2 axes in breast tumor invasion and metastasis. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-04-16.
Candida albicans septicaemia during first half of pregnancy successfully treated with 5-fluorocytosine.
Authors: J Schonebeck, E Segerbrand
Journal: BMJ (1973)

Cases of intrauterine candida infection during pregnancy are probably very grave and not too rare.They are likely to result in a dead fetus and a spontaneous abortion (Albarracin et al., 1967; Aterman, 1968; Lopez and Aterman, 1968; Ho and Aterman, 1970).In these cases the infection is generally