tbuckley/cabot-search huggingface dataset:
A Tbx1-Six1/Eya1-Fgf8 genetic pathway controls mammalian cardiovascular and craniofacial morphogenesis
Authors: Chaoshe Guo, Ye Sun, Bin Zhou, Rosalyn M. Adam, XiaoKun Li, William T. Pu, Bernice E. Morrow, Anne Moon, Xue Li
Journal: Journal of Clinical Investigation (2011)

Shared molecular programs govern the formation of heart and head during mammalian embryogenesis. Development of both structures is disrupted in human chromosomal microdeletion of 22q11.2 (del22q11), which causes DiGeorge syndrome (DGS) and velo-cardio-facial syndrome (VCFS). Here, we have identified a genetic pathway involving the Six1/Eya1 transcription complex that regulates cardiovascular and craniofacial development. We demonstrate that murine mutation of both Six1 and Eya1 recapitulated most features of human del22q11 syndromes, including craniofacial, cardiac outflow tract, and aortic arch malformations. The mutant phenotypes were attributable in part to a reduction of fibroblast growth factor 8 (Fgf8), which was shown to be a direct downstream effector of Six1 and Eya1. Furthermore, we showed that Six1 and Eya1 genetically interacted with Fgf8 and the critical del22q11 gene T-box transcription factor 1 (Tbx1) in mice. Together, these findings reveal a Tbx1-Six1/Eya1-Fgf8 genetic pathway that is crucial for mammalian cardiocraniofacial morphogenesis and provide insights into the pathogenesis of human del22q11 syndromes.
Correlates of Delayed Recognition and Treatment of Acute Type A Aortic Dissection
Authors: Kevin M. Harris, Craig E. Strauss, Kim A. Eagle, Alan T. Hirsch, Eric M. Isselbacher, Thomas T. Tsai, Hadas Shiran, Rossella Fattori, Arturo Evangelista, Jeanna V. Cooper, Daniel G. Montgomery, James B. Froehlich, Christoph A. Nienaber
Journal: Circulation (2011)

Background— In acute aortic dissection, delays exist between presentation and diagnosis and, once diagnosed, definitive treatment. This study aimed to define the variables associated with these delays. Methods and Results— Acute aortic dissection patients enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and January 2007 were evaluated for factors contributing to delays in presentation to diagnosis and in diagnosis to surgery. Multiple linear regression was performed to determine relative delay time ratios (DTRs) for individual correlates. The median time from arrival at the emergency department to diagnosis was 4.3 hours (quartile 1–3, 1.5–24 hours; n=894 patients) and from diagnosis to surgery was 4.3 hours (quartile 1–3, 2.4–24 hours; n=751). Delays in acute aortic dissection diagnosis occurred in female patients; those with atypical symptoms that were not abrupt or did not include chest, back, or any pain; patients with an absence of pulse deficit or hypotension; or those who initially presented to a nontertiary care hospital (all P &lt;0.05). The largest relative DTRs were for fever (DTR=5.11; P &lt;0.001) and transfer from nontertiary hospital (DTR=3.34; P &lt;0.001). Delay in time from diagnosis to surgery was associated with a history of previous cardiac surgery, presentation without abrupt or any pain, and initial presentation to a nontertiary care hospital (all P &lt;0.001). The strongest factors associated with operative delay were prolonged time from presentation to diagnosis (DTR=1.35; P &lt;0.001), race other than white (DTR=2.25; P &lt;0.001), and history of coronary artery bypass surgery (DTR=2.81; P &lt;0.001). Conclusions— Improved physician awareness of atypical presentations and prompt transport of acute aortic dissection patients could reduce crucial time variables.
Epigenetic Modification of CCAAT/Enhancer Binding Protein α Expression in Acute Myeloid Leukemia
Authors: Björn Hackanson, Kristi L. Bennett, Romulo M. Brena, Jinmai Jiang, Rainer Claus, Shih-Shih Chen, Nadya Blagitko-Dorfs, Katie Maharry, Susan P. Whitman, Thomas D. Schmittgen, Michael Lübbert, Guido Marcucci, Clara D. Bloomfield, Christoph Plass
Journal: Cancer Research (2008)

Abstract Functional loss of CCAAT/enhancer binding protein α (C/EBPα), a master regulatory transcription factor in the hematopoietic system, can result in a differentiation block in granulopoiesis and thus contribute to leukemic transformation. Here, we show the effect of epigenetic aberrations in regulating C/EBPα expression in acute myeloid leukemia (AML). Comprehensive DNA methylation analyses of the CpG island of C/EBPα identified a densely methylated upstream promoter region in 51% of AML patients. Aberrant DNA methylation was strongly associated with two generally prognostically favorable cytogenetic subgroups: inv(16) and t(15;17). Surprisingly, while epigenetic treatment increased C/EBPα mRNA levels in vitro, C/EBPα protein levels decreased. Using a computational microRNA (miRNA) prediction approach and functional studies, we show that C/EBPα mRNA is a target for miRNA-124a. This miRNA is frequently silenced by epigenetic mechanisms in leukemia cell lines, becomes up-regulated after epigenetic treatment, and targets the C/EBPα 3′ untranslated region. In this way, C/EBPα protein expression is reduced in a posttranscriptional manner. Our results indicate that epigenetic alterations of C/EBPα are a frequent event in AML and that epigenetic treatment can result in down-regulation of a key hematopoietic transcription factor. [Cancer Res 2008;68(9):3142–51]
Prognostic value of genetic alterations in children with first bone marrow relapse of childhood B-cell precursor acute lymphoblastic leukemia
Authors: S Krentz, J Hof, A Mendioroz, R Vaggopoulou, P Dörge, C Lottaz, J C Engelmann, T W L Groeneveld, G Körner, K Seeger, C Hagemeier, G Henze, C Eckert, A von Stackelberg, R Kirschner-Schwabe
Journal: Leukemia (2012)
The Nuremberg Code, German Law, and Prominent Physician-Thinkers-Reply
Authors: Jay Katz
Journal: JAMA (1997)

<h3>In Reply.</h3> —Citing from the abstract of my article, Dr Sass asserts that I have ignored the existence of the 1931 German Reich Regulation Concerning New Therapy and Human Experimentation and the 1900 directive of the Prussian Minister of Religious, Educational and Medical Affairs and then goes on to cite extensively from the former. But abstracts are not articles; these were precisely the codes addressing research ethics that I cited in the article (page 1663) as the only exceptions to the rule.
Preservation of basal AcSDKP attenuates carbon tetrachloride-induced fibrosis in the rat liver
Authors: Yuan-Wen Chen, Bo-Wei Liu, Yu-Jian Zhang, Ying-Wei Chen, Guo-Fang Dong, Xiao-Dong Ding, Lei-Ming Xu, Betty Pat, Jiang-Gao Fan, Ding-Guo Li
Journal: Journal of Hepatology (2010)
The in vivo melanocytotoxicity and depigmenting potency of N-2,4-acetoxyphenyl thioethyl acetamide in the skin and hair
Authors: M. JIMBOW, H. MARUSYK, K. JIMBOW
Journal: British Journal of Dermatology (1995)

It has been shown previously that N-acetyl-4-S-cysteaminylphenol (N-Ac-4-S-CAP) is a tyrosinase substrate and a potent depigmenting agent of dark skin and black hair. The present study evaluated the depigmenting potency of an acetyl derivative of N-Ac-4-S-CAP, N-2,4-acetoxyphenyl thioethyl acetamide (NAP-TEA) in the skin and hair. We tested for (i) in vitro metabolites in the skin after topical application, and (ii) in vivo depigmenting potency in the skin and hair. We found that NAP-TEA was stable in water, but was converted to N-Ac-4-S-CAP after topical application to human skin. Therefore, although NAP-TEA was not a tyrosinase substrate, it could react with tyrosinase after being converted to N-Ac-4-S-CAP by O-deacetylation in vivo. NAP-TEA produced marked depigmentation of dark skin (Yucatan pig) after daily topical application. When given by intraperitoneal injection, it resulted in complete loss of hair colour (white) grown at the epilated site in adult C57 black mice after daily administration for 10 days, and incomplete loss of coat colour (silver grey) in newborn C57 black mice after a single administration. The depigmentation of the skin and hair was reversible. Split-dopa preparation and electron microscopy indicated that this depigmentation is primarily related to (i) a marked decrease in the number of functioning melanocytes and melanized melanosomes, (ii) a decrease in the number of melanosomes transferred to keratinocytes, and (iii) selective degeneration/inactivation of melanocytes, and deposition of melanin-like material in the Golgi cisternae, coated vesicles and melanosomes, where tyrosinase is reported to be located. We propose the NAP-TEA is converted in vivo to N-Ac-4-S-CAP which, via interaction with tyrosinase, causes reversible depigmentation of the skin and hair.
The effect of nitrogen mustard intoxication on glucose absorption from the small intestine of the rat
Authors: M. J. Leibowitz, P. C. Merker
Journal: Gut (1971)

Methyl bis (β-chlorethyl) amine (HN<sub>2</sub>) was administered as a single intraperitoneal dose to male Sprague-Dawley rats. Animals were given either a median lethal dose and perfused one day after treatment or were given a larger dose and perfused two days after treatment. Intestinal segments were perfused <i>in vivo</i> and samples of effluent were collected and measured for glucose using the glucose oxidase method. Animals treated with the larger dose of HN<sub>2</sub> displayed significant reduction in intestinal dry weight. The average water content of intestinal segments derived from treated animals did not differ significantly from that in controls. Steady-state glucose absorption, obtained from data collected during the last 40 minutes of the perfusion period, was found to be significantly reduced in animals treated with drugs when intestinal absorption for control and treated animals was adjusted for water movement but not for dry intestinal weight and length. However, when glucose absorption was adjusted for dry tissue mass and length as well as for water movement, no significant differences in intestinal glucose absorption between control and treated rats were observed. Alterations can therefore be attributed to loss of intestinal tissue rather than to loss in the ability of the intestinal mass to absorb glucose.
THE BACTERIAL GROWTH INHIBITOR (LACTENIN) OF MILK
Authors: F. S. Jones, Henry S. Simms
Journal: The Journal of Experimental Medicine (1930)

The bacterial growth inhibitory substance found in milk is called lactenin in this paper. It is stable for 1½ hours at pH 4 and at pH 10 and for longer periods in neutral solution. It is not associated with salts and carbohydrates and may be separated from them by dialysis. Lactenin is removed by agents which precipitate the proteins of whey. Part of these proteins may be hydrolyzed by tryptic digestion and the resulting split products, together with the salts and sugar, may then be removed by dialysis without appreciable loss of lactenic activity. This dialysis may be performed in a concentrating dialyzer, under sterile conditions and at low temperature, thus reducing the solution to small volume. The material may then be completely desiccated and kept 3 months with practically no loss of activity. The residue, on treating this dried material with salt solution, is 200 times as active as the original milk, on a dry weight basis. The size of hemolytic zones of the scarlet fever streptococcus grown on a medium containing lactenin is found to furnish a simple and reliable measure of lactenic activity.
Preventing Neonatal Herpes
Authors: Nancy J. Binkin
Journal: JAMA (1984)

To reduce the occurrence of neonatal herpes, laboratory screening with viral cultures during the last four to eight weeks of pregnancy has been recommended as a way to recognize women with subclinical herpes infection at delivery. Screening efforts have focused on a group of high-risk women, especially those with recurrent genital herpes infection. Using the technique of decision analysis, we examined the benefits, risks, and costs of viral culture screening for women with recurrent genital herpes. In a cohort of 3.6 million women, we estimate that screening would avert 11.3 neonatal deaths and 3.7 cases of severe retardation, but 3.3 women would die as a result of cesarean deliveries necessitated by culture results. Weekly viral cultures would diagnose one fourth of women with subclinical recurrent infection at delivery. The cost per case averted would be approximately $1.8 million. Future screening recommendations should consider not only the number of cases averted but also the effectiveness of screening and the costs in both maternal lives and medical care dollars. (<i>JAMA</i>1984;251:2816-2821)
A CONVENIENT METHOD FOR FILING SURGICAL SECTIONS
Authors: W. L. Robinson
Journal: JAMA (1918)

We have experienced considerable difficulty in keeping our surgical sections properly filed in such manner that they might at all times be readily accessible, and at the same time have proper notes filed with them which could be indexed and cross-indexed. The filing of the sections in one set of drawers and the cards, with notes on these sections, in other drawers is not only an inconvenience but also involves unnecessary work. To obviate this we have mounted the section on the back of the filing card, in which a hole has been punched, to enable one to examine the section under the microscope while it is still attached to the card. An ordinary filing card, 4 by 6 inches, is used, and a hole seven-eighths inch in diameter is made with a steel punch in the center of the lower margin. The section is then pasted to the back
Acute Phlegmonous Caecitis
Authors: S. G. Nardell
Journal: BMJ (1949)

BICAL OURNALby mixing the grated coconut with hot water and manually squeezing out the oil.To reduce the fat content, the mothers were instructed not to add the milk obtained by the initial squeeze, but to discard this and add hot water to the grated coconut.This weaker coconut milk was used for the preparation of the child's curry.The fat-deficient diet was continued for a few weeks after the stools became normal.Summary Forty cases of pathologically proved E. histolytica infection in infants in Colombo and its environs are presented.Of 291 cases of infantile diarrhoea in children under 2 years of age 15.9% were infected with E. histolytica.Fourteen cases were 1 year of age and 26 between 1 and 2 years.Twenty-nine of the cases were infected with E. histolytica minuta and the others with the larger type.Half the cases were of the acute and half of the chronic and relapsing variety.Treatment given was by emetine parenterally and carbarsone orally.Of the cases followed up 80%/0 indicated satisfactory results.
Upper Gastrointestinal Bleeding From Leukemic Gastric Implants
Authors: J. Nackley, II, J. Barthel, D. Coppola
Journal: Endoscopy (2002)

Figure 1 A 23-year-old woman admitted with an acute myelogenous leukemic blast crisis, developed thrombocytopenia, melena, and anemia. An esophagogastroduodenoscopy was performed, revealing an erythematous, friable mucosa with multiple white plaques lining the entire gastric mucosa. A small feeding tube was in place
This House believes doctors are neglecting their duty to lead health service change: Proposer
Authors: A. Maynard
Journal: BMJ (2009)

At worst the doctor should do the patient no harm. At best they should practice EBM—in this case, economics based medicine—by focusing on the comparative cost effectiveness of competing interventions.1 EBM requires doctors to recognise the universal issue of opportunity cost, where a decision to treat one patient involves the denial of treatment to another patient. It also obliges the doctor to focus on value: the value of what they give up when they treat a patient (cost) and the value of what is gained as a result of treatment—hopefully improved length and quality of life for the patient. Clinical practice should …
Delayed Diuretic FDG PET/CT Scan Facilitates Detection of Renal Urothelial Cell Carcinoma
Authors: Chia-Lu Yeh, Shih-Wei Chen, Yen-Kung Chen
Journal: Clinical Nuclear Medicine (2009)

A 63-year-old woman presented with a recent complaint of painless hematuria. Cystoscopy showed no evidence of a bladder tumor. Renal ultrasound was negative. FDG PET/CT was performed under the suspicion of occult malignancy. The initial routine PET images seemed unremarkable, whereas the coregistered CT images revealed a soft tissue density lesion in the upper pelvis of the left kidney. On the delayed PET/CT scan of the kidneys after intravenous administration of furosemide and oral hydration, focal intense FDG uptake in the left upper renal pelvis was revealed. Thereafter, ureteroscopic biopsy of the left renal pelvic lesion was done and pathology confirmed high-grade urothelial cell carcinoma. This case demonstrated the usefulness of the delayed diuretic imaging technique for improving the visualization of tumor uptake in the renal collecting system by decreasing the urinary artifact. It is a simple, noninvasive, and easily performed method to facilitate detection of urinary tract tumors, especially when abnormal CT findings exist.
Reversal of Raynaud's Phenomenon
Authors: Richard P. Leavitt
Journal: JAMA (1979)

<h3>To the Editor.—</h3> It is a rare experience to find immediate clinical applicability of a technique reported in the latest issue of a medical journal. On Dec 15, 1978, having just read McIntyre's description of "A Maneuver To Reverse Raynaud's Phenomenon of the Fingers" (240:2760, 1978), I relayed specifics of his technique to a co-worker who has a long history of idiopathic Raynaud's phenomenon of the fingers, with attacks usually precipitated by exposure to cold and lasting 30 to 60 minutes. She is a commercial artist, needing continuous dexterity of her fingers, and has found immersion of fingers in warm water to provide unsatisfactorily inconvenient, unavailable, or slow relief. On the same day during which she was informed of McIntyre's recommendations, she had a Raynaud attack, apparently from hand contact with a cold steering wheel, and despite a delay of more than ten minutes, on arrival to a nonautomotive, private
Diverse virulence traits underlying different clinical outcomes of Salmonella infection
Authors: Joshua Fierer, Donald G. Guiney
Journal: Journal of Clinical Investigation (2001)

Nontyphoid Salmonella are a common cause of bacterial gastroenteritis, which is usually a self-limited illness in previously healthy adults (1).However, nontyphoid Salmonella can also cause a variety of life-threatening extraintestinal infections.A number of host factors can predispose to extraintestinal Salmonella infections, including AIDS, hemolytic anemias, and genetic defects that affect IL-12, IFN-γ, and the phagocyte NADPH oxidase, but even in the susceptible host, certain serotypes of Salmonella are more likely to cause systemic infections.These same serotypes are also more likely to cause invasive infections in people with no identifiable predisposing abnormalities.This review will concentrate on the differences among nontyphoid Salmonella that could account for the increased virulence of some serotypes or strains. Phenotypic and genetic differences among Salmonella strainsBased on iso-enzymes, rRNA sequences, and DNA hybridization, microbial taxonomists consider almost all of the Salmonella that infect mammals and birds to be one species (S. enterica) (2).There are six subspecies of S. enterica including enterica (I), salamae (II), arizonae (IIIa), diarizonae (IIIb), houtenae (IV), and indica (VI).S. bongori (V) is rarely isolated from clinical specimens and is considered to be a separate species (see below).Within these six subspecies are over 2,000 serotypes of Salmonella, as defined by the carbohydrate structures found in LPS and by flagella antigens.However, nearly all the serotypes that cause disease in humans and domestic animals belong to subspecies enterica (I).Despite the fact that they are genetically closely related, there is enormous variation in the virulence and epidemiology of different serotypes of S. enterica (I).For instance, most serotypes cause only gastroenteritis, while specific serotypes (S. typhi, S. paratyphi A and C, and S. sendai) cause enteric fever, and a few nontyphoid serovars, e.g., S. cholerae-suis and S. dublin, are more likely to cause bacteremia than diarrhea (3).Likewise, some Salmonella are either fully host-adapted (as in the case of S. typhi and S. pullorum, which are limited to people and chickens, respectively) or highly host adapted, as
Significance of changes in cerebral electrical activity at onset of cardiopulmonary bypass.
Authors: P E Kritikou, M A Branthwaite
Journal: Thorax (1977)

A study of 100 patients requiring open-heart surgery has been undertaken to ascertain whether prophylactic measures designed to minimise cerebral damage have influenced the incidence or severity of changes in cerebral electrical activity recorded at the onset of cardiopulmonary bypass. The incidence of change in cerebral electrical activity remains high but the severity of the disturbances has diminished as compared with a series investigated before prophylactic measures were introduced. Changes suggestive of cerebral depression were particularly notable in children under 10 years of age. The significance of these findings is discussed in the context of factors which might influence cerebral electrical activity at the onset of bypass.
Expression of NADH/NADPH Oxidase p22 <sup>phox</sup> in Human Coronary Arteries
Authors: Hiroshi Azumi, Nobutaka Inoue, Saori Takeshita, Yoshiyuki Rikitake, Seinosuke Kawashima, Yoshitake Hayashi, Hiroshi Itoh, Mitsuhiro Yokoyama
Journal: Circulation (1999)

Background —NADH/NADPH oxidase is an important source of superoxide in the vasculature. Recently, we found that polymorphism of the gene p22 phox , a critical component of this oxidase, is associated with a risk of coronary artery disease. The aim of this study was to investigate the localization of p22 phox in human coronary arteries and to examine its difference in expression between nonatherosclerotic and atherosclerotic coronary arteries. Methods and Results —Using coronary artery sections from autopsied cases (n=11), the expression of p22 phox was examined by immunohistochemistry and Western blotting. In nonatherosclerotic coronary arteries, p22 phox was weakly expressed, mainly in the adventitia. In atherosclerotic coronary arteries, intensive immunoreactivity was detected in neointimal and medial smooth muscle cells and infiltrating macrophages in hypercellular regions and at the shoulder region. Semiquantitative analysis and Western blotting showed that the expression of p22 phox in atherosclerotic coronary arteries was more pronounced than that in nonatherosclerotic arteries. Double staining revealed p22 phox expression in adventitial fibroblasts, smooth muscle cells, macrophages in the neointima and media, and endothelial cells. Conclusions —As atherosclerosis progressed, the expression of p22 phox increased through the vessel wall. p22 phox might participate in the pathogenesis and pathophysiology of atherosclerotic coronary disease.