tbuckley/cabot-search huggingface dataset:
Antibody-dependent complement-mediated cytotoxicity in sera from patients with HIV-1 infection is controlled by CD55 and CD59.
Authors: J Schmitz, J P Zimmer, B Kluxen, S Aries, M Bögel, I Gigli, H Schmitz
Journal: Journal of Clinical Investigation (1995)

Various immune mechanisms have been reported to contribute to the progressive destruction of Th cells in HIV-1-infected patients. Among these, complement mediated lysis of infected cells has been suggested. An increased sensitivity of lymphocytes from HIV-1-infected patients to lysis by monoclonal antibodies directed to MHC class I antigen and complement has been directly correlated with a decreased expression of the decay accelerating factor (CD55). It also has been reported that the expression of the membrane inhibitor of reactive lysis (CD59) is decreased during HIV-1 infection. We examined the effect of antibodies in the serum of HIV-1-positive individuals and normal human serum (NHS) as source of complement on several HIV-1-infected cell lines differing in their expression of CD55 and CD59. When HIV-1-infected target cells without membrane expression of CD55 and CD59 were used, a highly significant cytotoxic effect was observed in the presence of heat inactivated anti-HIV-1-positive sera and NHS, while heat-inactivated anti-HIV-1-negative sera and NHS were unable to induce cytolysis. Similar results were obtained using purified IgG isolated from HIV-1-positive sera and either NHS or guinea pig serum as source of complement. Lysis of HIV-1-infected cells correlated with expression of viral antigens on the cell surface. HIV-1-infected CD55 and CD59 positive target cells showed specific lysis, when the function of these molecules was abrogated by blocking antibodies to CD55 and CD59. The finding of anti-HIV-1-specific cytotoxic antibodies in sera from HIV-1-infected patients should be considered in the pathogenesis of the HIV-1-infection.
Reoperations in Cardiac Surgery
Authors: Berkeley Brandt
Journal: JAMA (1990)

Reference books and textbooks usually have the distinction of being slightly out-of-date by the time they are published.<i>Reoperations in Cardiac Surgery</i>is remarkable in that it is not only surprisingly up-to-date, but the first of its kind to deal with a rapidly changing but very current topic. Since 1953 when Gibbon first introduced the successful use of extracorporeal circulation, the field of cardiac surgery has made rapid advances. During the next two decades there was an exponential growth as new operations were described. That growth has left us with a new group of patients who need second, third, and even fourth operations. At present, reoperations may represent 10% of the average cardiac surgeon's practice, and this figure will probably increase yearly. Hence the need for such a reference book. The editors, J. Stark and A. D. Pacifico, are two well-known congenital heart defect surgeons. Do not assume, however, that
IRon overload screeNing tool (IRON): Development of a tool to guide screening in primary care
Authors: Arch G. Mainous, Vanessa A. Diaz, Charles J. Everett, Michele E. Knoll, Mary M. Hulihan, Althea M. Grant, Christine E. McLaren, Gordon D. McLaren
Journal: American Journal of Hematology (2011)

Iron overload is associated with significant morbidity and mortality yet is easily treated. The objective of this study was to create a tool that could be easily adapted to clinical practice that indicates the likelihood of a patient having undetected iron overload. We used the National Health and Nutrition Examination Survey (NHANES) 1999-2002 for US adults aged 20 years and older to build a model (unweighted n=8,779). We chose potential variables for inclusion that could be gathered by self-report or measured without laboratory data and were suggested by past literature on hemochromatosis and iron overload. We computed logistic regressions to create the scores by initially evaluating the variables' relationship with elevated ferritin and elevated transferrin saturation and then using odds ratios to correspond to scores. The resulting score on the IRon Overload ScreeNing Tool (IRON) was then validated with data on 13,844 adults in the NHANES III, 1988-94. Predictors in the final tool were age, gender, previous diagnoses of liver condition, osteoporosis or thyroid disease. The IRON score yielded an area under the curve (AUC) in the NHANES 1999-02 of 0.720 and an AUC of 0.685 in the NHANES III validation sample. The IRON score is a tool to assist in identification of patients with iron overload that has several qualities that make it attractive for use in clinical practice with an undifferentiated patient population including brevity, easily collected information and predictive ability comparable to other tools that help in directing screening.
The neonatal surgeon.
Authors: R B Zachary
Journal: BMJ (1976)

During  presentation of  Denis Browne medal to Douglas Stephens reference was made to Denis Browne's definition of  role of  paediatric surgeon: the aim of  paediatric surgeon is not to create a monopoly but to set a standard. Clearly Denis Browne was referring to current practice in Great Britain, since there are several countries in Europe in which most of  surgery of childhood is concentrated in  hands of paediatric surgeons, of whom there are very many. One has only to compare  number of paediatric surgeons in, for example, Poland with that in this country to appreciate  difference in approach. If paediatric surgeons are to set such a standard they can do so only if they have more experience of  surgery of children than  general surgeon; if they accept their responsi bilities for solving  problems involved in  work; and, in particular, if they pay attention to those aspects in which  surgery of childhood differs from  surgery of adults. The indications for operation in  various types of hernia,  management of childhood tumours,  timing and type of operation for undescended testis, are all examples in which  concentrated experience of  paediatric surgeon is an asset to management. If we accept our duty to set a standard in  care of these surgical conditions in childhood we accept without question that most of this type of surgery will in fact be undertaken by general surgeons, and rightly so. To plan otherwise would mean to increase vastly  number of paediatric surgeons with no special advantage. In contrast, my plea for neonatal surgery is that there should indeed be a monopoly, or near monopoly, in  hands of paediatric surgeons, most of whom will be dealing with a sufficient volume and variety of this work to justify  title of neonatal surgeons. In developing this line of thought it is appropriate to review briefly  number and range of neonatal surgical problems seen in  neonatal surgical ward of  paediatric surgical unit at  Sheffield Children's Hospital. I have reviewed critically  facilities available for this type of surgery in our unit to find out where we are failing and how we might improve  service.
Cardiac rehabilitation: Basic theory and application
Authors: H. J. N. Bethell
Journal: British Journal of Sports Medicine (1988)

by an independent observer, and these results are very close to those of Table 1.The similarity of the standard deviation, and the results of the pilot study, suggest that self-measurement is of similar accuracy to observer measured pulse rate.The lower mean RHR in those exercising at levels known to produce a cardiovascular training effect supports the hypothesis that the selfreported vigorous exercise levels were valid.The results on the average time for an episode of exercise might indicate that those with longer exercise sessions are possibly training less intensively.The fact that heavy manual exercise at work was not associated with a reduction in resting pulse rate would imply that exercise at work is of insufficient intensity to produce a training effect, a finding that has been reported elsewhere (Tuxworth et al, 1986).Thus, in summary, we have conducted a survey of vigorous exercise taking in a community, and validated it by use of a self-measured resting heart rate.We fould self- measured resting heart rate to be easy to measure and repeatable and would recommend its use in community surveys of exercise taking.
A Trial of Amitriptyline and Fluphenazine in the Treatment of Painful Diabetic Neuropathy
Authors: Carl M. Mendel, Robert F. Klein, David A. Chappell, Willard H. Dere, Barry J. Gertz, John H. Karam, Thomas N. Lavin, Carl Grunfeld
Journal: JAMA (1986)

We conducted a double-blind, placebo-controlled, crossover study of the effectiveness of amitriptyline and fluphenazine in alleviating the pain of diabetic peripheral neuropathy in six diabetic patients. Pain was evaluated by the patients with a graphic rating scale. A placebo response was found, but no additional effect of amitriptyline and fluphenazine was seen. Although the statistical power of this study was low, these data, when combined with a reevaluation of previous trials of amitriptyline and fluphenazine in the treatment of painful diabetic neuropathy, indicate that there is no justification for the use of these agents in the treatment of painful neuropathy outside of large, controlled clinical trials. Depression as a possible cause of this condition should not go unnoted or untreated.
842-5 Anemia is common in patients with heart failure seen in specialty and community cardiology clinics: Results from the STAMINA: HFP registry (study of anemia in a heart failure population)
Authors: Lynne E Wagoner, Javed Butler, Ron Oren, Jalal K Ghali, Ileana Pina, Alan Miller, J.Herbert Patterson, Mick O'Quigley, Carla A Sueta, Michael James, Shaival Kapadia, Christopher M O'Connor, Todd A Schwartz, Kirkwood F Adams
Journal: Journal of the American College of Cardiology (2004)
Association of a pulsatile blood flow pattern on coronary arteriography and short-term clinical outcomes in acute myocardial infarction
Authors: C.Michael Gibson, Juhana Karha, Sabina A Murphy, James A de Lemos, David A Morrow, Robert P Giugliano, Mathew T Roe, Robert A Harrington, Christopher P Cannon, Elliott M Antman, Robert M Califf, Eugene Braunwald
Journal: Journal of the American College of Cardiology (2004)
Abstract 4810: Identification of molecular markers of pathological vascular subtypes with differential sensitivity to therapies targeting the VEGF pathway
Authors: Beverly L. Falcon, Marguerita O'Mahony, Julie Stewart, Jiangang Liu, Janice A. Nagy, Qi Xue, Yong Pan, Cynthia Jeffries, Emma Hatten, Tim R. Holzer, Harold F. Dvorak, Aejaz Nasir, Bronek Pytowski, Laura Benjamin, Mark T. Uhlik
Journal: Cancer Research (2014)

Abstract Therapeutic targeting of the VEGF pathway has not matched the efficacy suggested by preclinical tumor models. To date, the limitations of this form of therapy stem either from inherent or acquired resistance of the tumor vasculature to the reduction of VEGF signaling. Previous studies have described morphological phenotypes of different blood vessel types in human and mouse tumors. Recapitulation of these vascular phenotypes with a surrogate Ad-VEGFA164 model has shown differential sensitivity of these vascular subclasses to inhibitors of the VEGF pathway. The goal of the current study was to identify molecular markers for the various subtypes of pathological vessels and to assess whether similar molecular signatures are found in blood vessels in mouse tumor models and human disease. Using the Ad-VEGF-A164 flank model, microarray analysis was performed to identify molecular markers at each time-point, representing distinct stages of vessel development and maturation. We identified unique gene signatures at the various time-points and confirmed differential expression of the genes by qRT-PCR and/or immunohistochemistry. We found that vascular markers such as CD31, Ang2, and Tie1 were pan-endothelial markers at all time-points. However, other markers such as CD34, MECA-32, vWF, SMA, Tie2, CD105, and AQP1 were expressed on subclasses of endothelial cells. Expression of the molecular markers in tumors models revealed different subclasses of tumor vessels in patient-derived xenografts which were sensitive or resistant to anti-VEGF-A or anti-VEGFR-2 treatment. These vascular subtypes were also found in tissues from human breast and gastric cancers. Together these results indicate that multiple molecular markers can be used to identify unique pathological subclasses of tumor vessels. Some of these vascular subtypes may be insensitive to inhibitors targeting the VEGF pathways and their signatures may be useful biomarkers to predict vascular sensitivity to anti-angiogenic therapy. Citation Format: Beverly L. Falcon, Marguerita O'Mahony, Julie Stewart, Jiangang Liu, Janice A. Nagy, Qi Xue, Yong Pan, Cynthia Jeffries, Emma Hatten, Tim R. Holzer, Harold F. Dvorak, Aejaz Nasir, Bronek Pytowski, Laura Benjamin, Mark T. Uhlik. Identification of molecular markers of pathological vascular subtypes with differential sensitivity to therapies targeting the VEGF pathway. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4810. doi:10.1158/1538-7445.AM2014-4810
Occult ischaemic necrosis of skeletal muscle associated with renal failure.
Authors: J H Coakley, R H Edwards, P McClelland, J M Bone, T R Helliwell
Journal: BMJ (1990)

Acute renal failure associated with myoglobinuria may occur after traumatic and non-traumatic muscle damage.'2We report on three patients who developed acute renal failure with histological and biochemical evidence of muscle damage.
Postencephalitic Parkinson Syndrome after Meningoencephalitis Due to Coxsackie Virus Group B, Type 2
Authors: John H. Walters
Journal: New England Journal of Medicine (1960)

THE purpose of the present communication is to A report a case of meningoencephalitis in which Coxsackie virus Group B, Type 2, was isolated from the stools and in which a significantly high and further-rising antibody titer was demonstrated during the early course of an illness that did not terminate in recovery but resulted in a still persisting and progressing disability.Since the discovery of the Coxsackie viruses by Dalldorf and Sickles1 in 1948 and the subsequent isolation of at least 24 types of ECHO viruses, an increasing correlation of diseases with these initially "orphaned" agents has taken place. No . . .
Demeclocycline-Induced Nephrogenic Diabetes Insipidus
Authors: Irwin Singer, Donald Rotenberg
Journal: Annals of Internal Medicine (1973)

Renal concentrating defects were found in 8 out of 24 patients treated with demeclocycline for acne. By evaluation of maximum and minimum urine osmolalities, free-water clearance (CH2O), and solute-free water reabsorption (TCH2O), in three of five symptomatic patients the defect was determined to be nephrogenic, dose-dependent, and reversible. A dose-dependent, reversible defect in antidiuretic hormone (ADH)-induced water flow was also produced by demeclocycline in gravimetric studies with paired toad urinary hemibladders. This defect in ADH responsiveness was probably located at the serosal surface and was probably caused by impairment of both cyclic-AMP generation and action.
Portal and peripheral blood short chain fatty acid concentrations after caecal lactulose instillation at surgery.
Authors: S G Peters, E W Pomare, C A Fisher
Journal: Gut (1992)

The major end products of fermentation, short chain fatty acids (acetate, propionate, butyrate) were measured in portal and peripheral venous blood after the caecal instillation of lactulose at surgery in patients undergoing elective cholecystectomy. Blood samples for short chain fatty acid measurement were taken before and at 15 minute intervals up to 60 minutes after caecal instillation of either 20 ml sterile saline or 6.7 g or 10 g lactulose. Fasting concentrations (n = 28) were (mumol/l, mean (SD)); portal acetate 128.0 (70.8), propionate 34.4 (23.3), butyrate 17.6 (18.4); peripheral acetate 67.0 (23.0), propionate 3.7 (1.2), butyrate traces only. After lactulose there was a rapid rise in portal short chain fatty acids with peak concentrations being reached in 15 to 45 minutes. Mean peak concentrations (mumol/l (SD)) after 10 g lactulose were acetate 240.9 (142.2), propionate 39.0 (17.8) and butyrate 26.9 (17.6). The changes in acetate concentrations seen in portal blood were reflected in peripheral blood acetate measurements. In contrast with portal blood, only small amounts of propionate and traces of butyrate were found in peripheral blood.
Abstract 14119: A Novel Antibody-Targeted Recombinant Plasminogen Activator Directed to Activated Platelets Allows Efficient Antithrombotic Prophylaxis
Authors: Christoph E Hagemeyer, Xiaowei Wang, Jan-David Hohmann, Dexing Huang, Fu Jia, Karlheinz Peter
Journal: Circulation (2011)

Introduction: Plasminogen activators such as Urokinase (scuPA) generate plasmin, which lyses fibrin and restores perfusion. However, thrombi recur due to vascular damage and inflammation. Prophylac...
Other Voices Weigh In on Mammography Decision
Authors: Charles Marwick
Journal: JAMA (1997)

IN YET another attempt to resolve the controversy over when women in their 40s should be recommended to undergo routine mammographic screening for breast cancer, the advisory board of the National Cancer Institute (NCI) has set up a subcommittee charged with preparing a set of recommendations intended to help in making the difficult choice about whether and when to have a mammogram. From the comments at a press conference held after the board's decision, what will probably emerge is individualized advice, not blanket recommendations. There are unlikely to be firm, definitive guidelines on precisely when to start routine mammographic screening. This result will not satisfy those who want clear-cut answers or third-party payers unwilling to reimburse for any procedure without authoritative evidence of its value. The subcommittee's recommendations will be completed "in a timely manner, in the next couple of months before the board meets in June," said Barbara K.
Abstract 3850: The interaction of RUNX1 with CBFβ-SMMHC during leukemogenesis.
Authors: Ling Zhao, R Katherine Hyde, Lemlem Alemu, P Paul Liu
Journal: Cancer Research (2013)

Abstract Chromosome 16 inversion is associated with acute myeloid leukemia subtype M4Eo and produces a fusion gene CBFB-MYH11 that contains part of the core binding factor (CBF) β gene CBFB, and part of the smooth muscle myosin heavy chain (SMMHC) gene MYH11. This fusion gene encodes a fusion protein CBFβ-SMMHC, which is oncogenic and binds to the runt domain (RD) of RUNX1, another member of the CBF transcription factor family, resulting in repression of RUNX1 transactivation. We have generated mouse models by conventional and conditional knock-in of the Cbfb-MYH11 fusion gene and demonstrated that Cbfb-MYH11 represses Runx1 function in hematopoiesis and predisposes mice to myeloid leukemia (Castilla et. al., Cell 1996; Nat Genet, 1999). RUNX1 binding and repression was previously considered a key step in leukemogenesis by CBFβ-SMMHC. In order to dissect the molecular mechanism of RUNX1 and CBFβ-SMMHC interaction during leukemogenesis, we generated a knock-in mouse model with deleted high affinity binding site of Cbfb-MYH11. We found accelerated leukemia development in these mice (Kamikubo et.al., Cancer cell, 2010) suggesting that Cbfb-MYH11 play an independent role apart from Runx1 binding and repression. To test if Runx1 is involved in the leukemia development and progression, we crossed Cbfb-MYH11 knock-in mice with mice harboring one of the two mutant alleles of Runx1 - Runx1+/- and Runx1+/Lzd. Runx1+/- contains a null allele while Runx1+/Lzd contains a knocked-in fusion between the RD of Runx1 and the LacZ gene, which is partially dominant-negative in reporter assays. We have determined the rate and percentage of leukemia development in these mice. We found that the Cbfb-MYH11 mice that were Runx1+/- had a similar rate of leukemogenesis when compared with Cbfb-MYH11 mice that were Runx1+/+. However, the Cbfb-MYH11 mice that were Runx1+/Lzd had significantly delayed leukemogenesis as compared to Cbfb-MYH11 mice that were Runx1+/+. Moreover, some of the Cbfb-MYH11; Runx1+/Lzd mice did not develop leukemia at the end of the one-year observation. We detected a decrease of BrdU incorporation in the bone marrow cells in mice with the Runx1+/Lzd allele, suggesting that the delayed leukemia development resulted, at least in part, from decreased proliferation. These data demonstrated that Runx1 is likely required for leukemogenesis by CBFβ-SMMHC. Citation Format: Ling Zhao, R Katherine Hyde, Lemlem Alemu, P Paul Liu. The interaction of RUNX1 with CBFβ-SMMHC during leukemogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3850. doi:10.1158/1538-7445.AM2013-3850
Prophylaxis and Treatment of Influenza
Authors: John A. Oates, Alastair J.J. Wood, R. Gordon Douglas
Journal: New England Journal of Medicine (1990)

IT has been over 20 years since there has been a severe influenza pandemic. Nevertheless, influenza remains an important epidemic viral infection with the potential to return to its former magnitude.1 2 3 4 The Centers for Disease Control documented 10,000 or more excess deaths in the United States in each of 19 epidemics from 1957 to 1986, and more than 40,000 deaths in several of them.5 The major causes of death are pneumonia and the exacerbation of cardiopulmonary and other conditions,6 7 8 9 10 and 80 to 90 percent of those who die are 65 years of age or older. In addition, substantial morbidity occurs . . .
Selective Loss of AKR1C1 and AKR1C2 in Breast Cancer and Their Potential Effect on Progesterone Signaling
Authors: Qing Ji, Chisa Aoyama, Yih-Dar Nien, Paul I. Liu, Peter K. Chen, Lilly Chang, Frank Z. Stanczyk, Andrew Stolz
Journal: Cancer Research (2004)

Abstract Progesterone plays an essential role in breast development and cancer formation. The local metabolism of progesterone may limit its interactions with the progesterone receptor (PR) and thereby act as a prereceptor regulator. Selective loss of AKR1C1, which encodes a 20α-hydroxysteroid dehydrogenase [20α-HSD (EC 1.1.1.149)], and AKR1C2, which encodes a 3α-hydroxysteroid dehydrogenase [3α-HSD (EC 1.1.1.52)], was found in 24 paired breast cancer samples as compared with paired normal tissues from the same individuals. In contrast, AKR1C3, which shares 84% sequence identity, and 5α-reductase type I (SRD5A1) were minimally affected. Breast cancer cell lines T-47D and MCF-7 also expressed reduced AKR1C1, whereas the breast epithelial cell line MCF-10A expressed AKR1C1 at levels comparable with those of normal breast tissues. Immunohistochemical staining confirmed loss of AKR1C1 expression in breast tumors. AKR1C3 and AKR1C1 were localized on the same myoepithelial and luminal epithelial cell layers. Suppression of ARK1C1 and AKR1C2 by selective small interfering RNAs inhibited production of 20α-dihydroprogesterone and was associated with increased progesterone in MCF-10A cells. Suppression of AKR1C1 alone or with AKR1C2 in T-47D cells led to decreased growth in the presence of progesterone. Overexpression of AKR1C1 and, to a lesser extent, AKR1C2 (but not AKR1C3) decreased progesterone-dependent PR activation of a mouse mammary tumor virus promoter in both prostate (PC-3) and breast (T-47D) cancer cell lines. We speculate that loss of AKR1C1 and AKR1C2 in breast cancer results in decreased progesterone catabolism, which, in combination with increased PR expression, may augment progesterone signaling by its nuclear receptors.