tbuckley/cabot-search huggingface dataset:
High-Energy Phosphate Metabolism and Creatine Kinase in Failing Hearts
Authors: Yun Ye, Guangrong Gong, Koichi Ochiai, Jingbo Liu, Jianyi Zhang
Journal: Circulation (2001)

Background —This study aimed to create a pig model of heart failure secondary to severe aortic stenosis and to examine the relationship between the alterations in myocardial high-energy phosphate (HEP) metabolism and protein expression of creatine kinase (CK) isoforms. Methods and Results —Sixteen pigs with left ventricular hypertrophy (LVH) secondary to ascending aortic banding and 10 normal pigs (N) were studied. Myocardial protein levels of CK isoforms (Western blot), HEP levels, and CK kinetics ( 31 P MR spectroscopy) were measured under basal conditions. Nine of the 16 animals with LVH developed congestive heart failure (CHF), as evidenced by ascites (100 to 2000 mL). LV weight/body weight ratio (g/kg) was 2.18±0.15 in N hearts, 3.04±0.14 in hearts with LVH ( P &lt;0.01), and 4.23±0.36 in hearts with CHF ( P &lt;0.01 versus LVH). Right ventricle weight/body weight ratio and LV end-diastolic pressure were significantly higher in hearts with CHF (each P &lt;0.01 versus N or LVH). Myocardial phosphocreatine/ATP ratios and the CK forward flux rates were decreased in LVH hearts, most severely in hearts with CHF. CK-M/β-actin ratios were 2.21±12 (N), 1.69±0.15 (LVH), and 1.39±0.27 (CHF, P &lt;0.05 versus N). CK-mitochondria (CK-Mt)/β-actin ratios were 1.40±0.09 (N), 1.24±0.09 (LVH), and 1.02±0.08 (CHF, P &lt;0.05 versus N or LVH). The severity of the reduction of CK flux rate was linearly related to the severity of the decrease of CK-Mt/β-actin ( r =0.68, P &lt;0.01). Conclusions —In this new model of heart failure/hypertrophy, the abnormal myocardial HEP metabolism is related to the decreased CK-Mt protein level, which in turn is related to the severity of the hypertrophy.
Most practices would use open access spirometry in hospitals
Authors: L J Dowson, A Yeung, M B Allen
Journal: BMJ (1998)

EDITOR–Abbasi highlights the importance of spirometry in the assessment of patients with chronic obstructive pulmonary disease.1Guidelines published recently by the British Thoracic Society encourage the wider provision of this service by general practitioners.2We have recently performed an audit that identified issues that need to be considered if these proposals are to be implemented.

We surveyed general practices in North Staffordshire that serve a total population of 500 000 in order to define the provision of spirometry before …
Upper Extremity Venous Thrombosis
Authors: Robert J. Hall
Journal: JAMA (1974)

ABSTRACT To the Editor.— The recent article Upper Extremity Venous Thrombosis With Pulmonary Embolism: A Complication of Excretory Urography (227:187, 1974) by Clagett et al drew my interest. In a review of 23 patients with primary subclavian-axillary vein thrombosis seen over a 16-year period at Walter Reed General Hospital, Washington, DC (Swinton et al, Circulation 38:737, 1968), we identified one certain and one probable pulmonary embolus resulting from primary upper extremity venous thrombosis: the former case has been previously reported by A. H. Aufses, Jr (Surgery 35:957, 1954). In addition, the potential for precipitation of venous complications following intravenous infusion of radiopaque media was observed in two patients. One suffered a transient chemical phlebitis and exacerbation of symptoms in the affected arm following phlebography; the other developed severe basilic-cephalic-antecubital chemical phlebitis in the contralateral normal extremity following bilateral diagnostic phlebography three months after the onset of the primary axillary thrombosis. We concluded
Molecular and functional changes in spectrin from patients with hereditary pyropoikilocytosis.
Authors: W J Knowles, J S Morrow, D W Speicher, H S Zarkowsky, N Mohandas, W C Mentzer, S B Shohet, V T Marchesi
Journal: Journal of Clinical Investigation (1983)

The structural and functional properties of spectrin from normal and hereditary pyropoikilocytosis (HPP) donors from the two unrelated families were studied. The structural domains of the spectrin molecule were generated by mild tryptic digestion and analyzed by two-dimensional electrophoresis (isoelectric focusing; sodium dodecyl sulfate-polyacrylamide gel electrophoresis). The alpha I-T80 peptide (Mr 80,000) is not detectable in two related HPP donors; instead, two new peptides (Mr 50,000 and 21,000) are generated and have been identified as fragments of the normal alpha I-T80. A third sibling has reduced levels of both the normal alpha I-T80 and the two new peptides. A similar analysis of spectrin from another HPP family indicates that their spectrins contain reduced amounts of the alpha I-T80 and the 50,000 and 21,000 fragments of the alpha I domain. The HPP donor also has other structural variations in the alpha I, alpha II, and alpha III domains. The alpha I-T80 domain of normal spectrin has been shown to be an important site for spectrin oligomerization (J. Morrow and V.T. Marchesi. 1981. J. Cell Biol. 88: 463-468), and in vitro assays indicate that HPP spectrin has an impaired ability to oligomerize. Ghost membranes from HPP donors are also more fragile than membranes from normal erythrocytes when measured by ektacytometry. In both the oligomerization and fragility assays, the degree of impairment is correlated with the amount of normal alpha I-T80 present in the spectrin molecule. We believe that a structural alteration in the alpha I-T80 domain perturbs normal in vivo oligomerization of spectrin, producing a marked decrease in erythrocyte stability.
Acute Pancreatitis in Children
Authors: B. Wolman
Journal: BMJ (1962)

Inflammation of the pancreas is rare in children and as a result may be forgotten in considering the differential diagnosis of abdominal pain, except in mumps, when nausea, vomiting, epigastric pain, and sometimes collapse suggest acute pancreatitis.Most patients recover in two or three days.Apart from this, trauma (Venable, 1932;Adams, 1939;Shallow and Wagner, 1947) and disease of the biliary tract (Dobbs, 1935) may occasionally produce haemorrhagic or suppurative pancreatitis.However, these cases are few, and by far the greatest number of recorded cases have a non-specific or unidentified aetiology (Haigh, 1956; Blumenstock, Mithoefer, and Santulli, 1957).In the last four years, three children suffering from acute pancreatitis of "non-specifics' origin have been seen, and a review of the cases and the problems involved are worth discussing.Case 1A boy aged 10 was first seen in November, 1957, when sent into hospital with a diagnosis of acute appendicitis because of generalized severe abdominal pain and vomiting of two days' duration.On examination he had tenderness and rigidity in the right hypochondrium but no rebound tenderness.His temperature was 990 F. (37.2°C.) and the blood count was normal.At operation the appendix was retrocaecal but not inflamed.The pancreas was found to be enlarged and surrounded by many enlarged mesenteric glands.Some free fluid was present Appendicectomy was performed, but the diagnosis of pancreatitis was queried.The serum amylase was found to be 80 Wohlgemuth units.Chole- cystograms, done later, showed no abnormality in the gall-bladder or bile-duct.
The Effects of Omalizumab on the Late-Phase Response to Nasal Allergen Challenge
Authors: M.O. Paterniti, L.M. Breslin, P.M. Sterba, M.E. Brummet, Y. Park, D.W. MacGlashan Jr., B.S. Bochner, S.S. Saini
Journal: Journal of Allergy and Clinical Immunology (2011)
The Curse: A Cultural History of Menstruation
Authors: Felicia Hance Stewart
Journal: JAMA (1989)

Reexamining old assumptions can be a source of vitality and progress in the process of scientific inquiry. Undertaking rediscovery is perhaps most important for assumptions so long held and deeply embedded that their very existence is unsuspected, their specificity not articulated. In this respect,<i>The Curse: A Cultural History of Menstruation</i>is an extremely important work. Delaney, Lupton, and Toth offer pioneering scholarship as they explore an extraordinary range of hidden assumptions and attitudes about menstruation. Menstrual periods underscore approximately one fourth of the life experience of (young) adult women. The fact that this process has remained so long shrouded, unmentionable, and substantially ignored even in scientific inquiry or medicine is a measure of the power of the taboos the authors describe. <i>The Curse</i>first appeared in 1976 and has been revised and expanded to include new material from the last decade (including a tiny bit of progress in reducing
Upper urinary tract pacemaker cells join the GLI club
Authors: Doris Herzlinger
Journal: Journal of Clinical Investigation (2011)

Mutations in GLI3, a component of the Sonic Hedgehog (Shh) signaling pathway, cause a variety of human developmental syndromes. In this issue of the JCI, Cain and colleagues show that tightly regulated GLI3 repressor activity is essential for Shh-dependent differentiation of upper urinary tract pacemaker cells and the efficient flow of urine from the kidney to the bladder. These results link defective pacemaker cell differentiation with hydronephrosis and provide a cellular basis for one of the abnormal renal defects observed in humans with the GLI3-linked disease Pallister-Hall syndrome.
Preventing Visual Loss From Chronic Eye Disease in Primary Care
Authors: Susannah Rowe, Catherine H. MacLean, Paul G. Shekelle
Journal: JAMA (2004)

Vision loss is common in the United States and its prevalence increases with age. Visual disability significantly impacts quality of life and increases the risk of injury. Although at least 40% of blindness in the United States is either preventable or treatable with timely diagnosis and intervention, many people with vision loss are undiagnosed and untreated.To review the evidence regarding screening and management of eye disorders and visual disability among adults in the primary care setting.MEDLINE, HealthSTAR, EMBASE, The Cochrane Database of Systematic Reviews, and the National Guidelines Clearinghouse were searched for articles and practice guidelines about screening and management of eye diseases and vision loss among adults in the primary care setting using key words and free-text terms, such as vision screening, glaucoma prevention and control, from 1985 to 2003. References in these articles and those suggested by experts in eye care, vision loss, and vision screening were reviewed as well.Articles were searched for the most clinically important information and emphasized randomized controlled trials where available.Most major guidelines recommend periodic referral of older adults to an eye care professional for comprehensive evaluation to detect eye diseases and visual disability. The value of routine screening for vision loss in the primary care setting has not been established. Timely identification and treatment of eye diseases can substantially reduce the incidence and prevalence of visual disability among older adults. Optimizing management of systemic diseases, such as diabetes, hypertension, and hyperlipidemia, significantly reduces the risk of related eye disorders.Primary care clinicians can play a vital role in preserving vision in their patients by managing systemic diseases that impact eye health and by ensuring that patients undergo periodic evaluations by eye care professionals and receive needed eye care.
Antibiotic resistance patterns in coagulase-negative staphylococci after treatment with topical erythromycin, benzoyl peroxide, and combination therapy
Authors: KAREN S. HARKAWAY, K. J. McGINLEY, ARLENE N. FOGLIA, WEI-LI LEE, FERN FRIED, A. R. SHALITA, J. J. LEYDEN
Journal: British Journal of Dermatology (2008)

Summary Antibiotic resistance of the resident cutaneous bacterial flora is a well recognized consequence of systemic antibiotic therapy. In this study, we followed the development of antibiotic resistance of coagulase-negative staphylococci (CNS), the most numerous aerobic bacteria found on the skin surface, during treatment with three topical antimicrobial agents used to treat acne vulgaris. Groups of 20 subjects received either topical erythromycin, benzoyl peroxide or a combination of the two for 16 weeks. After 12 weeks of treatment with erythromycin, the aerobic flora was dominated by S. epidermidis which was completely resistant to erythromycin. In addition there was an increase in resistance to clindamycin and tetracycline. Treatment with benzoyl peroxide and the combination of erythromycin and benzoyl peroxide resulted in a significant reduction in the number of aerobic bacteria without any change in the resistance pattern to erythromycin or other antibiotics.
808. Optimizing Non-Primate Lentiviral Vectors for Gene Transfer of CFTR to Airway Epithelia
Authors: Jessica D. Goreham-Voss, Patrick L. Sinn, Melissa A. Hickey, Ariadna Arias, Paul B. McCray
Journal: Molecular Therapy (2006)

Suboptimal expression from Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) cDNA delivered by viral vectors has, in part, limited the use of gene transfer as a therapy for cystic fibrosis. Previously we described a lentiviral vector developed from feline immunodeficiency virus (FIV) pseudotyped with baculovirus GP64 which transduces nasal epithelia in mice and persistently expresses a reporter gene. The goal of the current project is to further improve transgene expression levels through several modifications to this FIV vector, and to test the optimized vector's effects on protein expression. Modifications include rendering the lentiviral vector |[ldquo]|self-inactivating|[rdquo]| by deleting the U3 region of the 3’ LTR, thus providing a layer of safety. The FIV central polypurine tract (cPPT) element was inserted upstream of the internal promoter and the woodchuck hepatitis virus posttranscriptional regulatory element (wPRE) was incorporated downstream of the reporter gene. Also, two sites were mutated, a major splice donor and the start codon of the partial Gag sequence, preventing production of undesired product. In addition, a newly identified post- transcriptional control element from the 5’ LTR of spleen necrosis virus (SNVU5) was incorporated into the delivery vector. The Rous sarcoma virus promoter and the reporter gene, firefly luciferase, were used to test relative expression of the intermediate vectors in the production of the optimized FIV vector. Expression was quantified in two model systems transduced with modified FIV lentiviral vector: cultured HT1080 cells and Balb/c mice. As determined by luciferase activity assay, in vitro transductions with intermediate vectors showed an enhanced luciferase expression with wPRE and SNVU5, but no enhanced expression with the addition of cPPT. As determined by CCD camera detection of bioluminescence in vivo, both the wPRE and SNVU5 elements significantly increased luciferase expression in the FIV lentiviral vector, but the cPPT did not. The optimized and intermediate vectors were used to deliver the CFTR gene, and expression was detected by real-time PCR targeting CFTR mRNA. The optimized vector produced approximately 20-fold increase in CFTR mRNA as compared with the control vector. Vector constructs with epithelial specific promoters will be used to transduce airway epithelia in vitro and in vivo, and the contribution of the promoter to expression levels, persistence, and cell specific expression will be assessed. The long-term goal is to use an optimized viral vector construct to express sufficient CFTR protein in the airways of humans with cystic fibrosis to correct the chloride ion transport defect.
Long-term effects of knitted silk–collagen sponge scaffold on anterior cruciate ligament reconstruction and osteoarthritis prevention
Authors: Weiliang Shen, Xiao Chen, Yejun Hu, Zi Yin, Ting Zhu, Jiajie Hu, Jialin Chen, Zefeng Zheng, Wei Zhang, Jisheng Ran, Boon Chin Heng, Junfeng Ji, Weishan Chen, Hong-Wei Ouyang
Journal: Biomaterials (2014)
Malta (Remittent) Fever
Authors: Chas. C. Godding
Journal: BMJ (1891)

efinition.--A1)aroxysmal fever witlh daily remissionis.General Observ (tions.-Tencases occurred in 1888 aand 2)' in 1890.Relapses are excluded.The temperature clharts given are limit(d to tile f(ist few days.For the purposes of descrip- tion I will divide tle (lisease into tlhree types; these types.however, nearly always running one into the other.I.-ENTERIC TYPE,.C. 1,., ageled 21, stoker, on Junie 1ltlh, 1890, complained of severe rleumn.aticpains in the rigiht tlhigh, otherwise lie felt well.Profuse sweats occurred oln the nights of June 12th to 16th.1Purging and pains in the epigastrium on June 1ltll to 18th, lasting about 20lhours and Inot reculrring till June 25th, when the stools were formed.(See Clhart 1.) Tlhei enteiie JUNE 1890,
Prevalence and Long-Term Outcome of Aortic Prosthesis–Patient Mismatch in Patients With Paradoxical Low-Flow Severe Aortic Stenosis
Authors: Dania Mohty, Cyrille Boulogne, Julien Magne, Philippe Pibarot, Najmeddine Echahidi, Elisabeth Cornu, Jean Dumesnil, Marc Laskar, Patrice Virot, Victor Aboyans
Journal: Circulation (2014)

Patients with severe aortic stenosis (AS) and paradoxical low flow (PLF) have worse outcome compared with those with normal flow. Furthermore, prosthesis-patient mismatch (PPM) after aortic valve replacement is a predictor of reduced survival. However, the prevalence and prognostic impact of PPM in patients with PLF-AS are unknown. We aimed to analyze the prevalence and long-term survival of PPM in patients with PLF-AS.Between 2000 and 2010, 677 patients with severe AS, preserved left ventricular ejection fraction, and aortic valve replacement were included (74±8 years; 42% women; aortic valve area, 0.69±0.16 cm(2)). A PLF (indexed stroke volume ≤35 mL/m(2)) was found in 26%, and after aortic valve replacement, 54% of patients had PPM, defined as an indexed effective orifice area ≤0.85 cm(2)/m(2). The combined presence of PLF and PPM was found in 15%. Compared with patients with noPLF/noPPM, those with PLF/PPM were significantly older, with more comorbidities. They also received smaller and biological bioprosthesis more often (all P<0.01). Although early mortality was not significantly different between groups, the 10-year survival rate was significantly reduced in case of PLF/PPM compared with noPLF/noPPM (38±9% versus 70±5%; P=0.002), even after multivariable adjustment (hazard ratio, 2.58; 95% confidence interval, 1.5-4.45; P=0.0007).In this large catheterization-based study, the coexistence of PLF-AS before surgery and PPM after surgery is associated with the poorest outcome.
Instability of beta E-messenger RNA during erythroid cell maturation in hemoglobin E homozygotes.
Authors: J Traeger, P Winichagoon, W G Wood
Journal: Journal of Clinical Investigation (1982)

Hemoglobin E interacts with beta-thalassemia to produce a disorder of variable severity that is the most common form of symptomatic thalassemia in Southeast Asia. The beta E-globin gene acts as a mild thalassemia gene; there are low levels of beta E-messenger RNA (mRNA) in reticulocytes, and preliminary evidence had suggested that this might be due to instability of the beta E-mRNA. Analysis of beta E-mRNA levels in the nuclei and cytoplasm of bone marrow erythroblasts compared with reticulocytes has shown higher levels of beta E-mRNA in the former, providing direct evidence that this is the case.
Teenager with an irritable hip, anaemia and malaise.
Authors: R Hertzberger-ten Cate, B A Dijkmans, F C Breedveld
Journal: Annals of the Rheumatic Diseases (1995)

We have described a boy with a juvenile spondyloarthropathy who also showed inflammatory changes in the gut. Gastrointestinal symptoms initially indicated the presence of an inflammatory bowel disease, but this was excluded histopathologically.
Knockdown of c-Jun N-terminal kinase 1 expression in murine mammary cancer cells leads to an increase in tumor growth and bone metastasis.
Authors: A Nasrazadani, S Mitra, C Van Den Berg
Journal: Cancer Research (2009)

Abstract Abstract #1156 The c-Jun N-Terminal Kinase (JNK) family of proteins are involved in cell proliferation and apoptosis depending on the specific isoform, cell type, and activating stimuli. The JNK proteins are known as the predominant c-Jun kinases, resulting in AP-1 activation and increased expression of AP-1 transcriptional targets. More specifically, it has been reported that osteoclast differentiation is impaired in jnk1-/- mice. The purpose of this study was to determine whether expression of JNK1 in cancer cells will influence the bone microenvironment during metastatic growth. The 4T1.2 murine mammary cancer cell line was studied as an established model for mammary cancer mediated bone metastasis. Using a JNK1α1 shRNA approach, we observed 75% reduction in expression Orthotopic injection of the shJNK1α1 cells into the mammary fat pad of Balb/c mice significantly increased tumor growth rates and shortened survival compared to the respective empty vector cell line (p&amp;lt;0.0001). Similarly, intra-cardiac injection of the shJNK1α1 cells led to a significant decrease in survival (p=0.003) and an increase in incidence of metastatic lesions in the ribcage (p=0.04). Serum levels of Cathepsin K were assayed as an indicator of bone resorption and was significantly higher in the mice injected with the knockdown cells compared to empty vector controls (p=0.03). Finally, immunohistochemical analysis of bone lesions showed higher expression of ADAM (A Disintegrin and Metalloproteinase) 10 suggesting that the more aggressive phenotype observed with the shJNK1a1 cells may be attributed to the increase in ADAM10 protein expression. Previous studies have shown that ADAM10 that cleaves RANKL into its active soluble form. Further, RANKL expression has been reported to be elevated in breast carcinomas, resulting in osteolysis during metastasis. Indeed our qPCR analysis detected an approximate 2 fold increase in RANKL levels in the shJNK1α1 cells, consistent with this assertion. In summary, these data support that reduction in JNK1a1 expression enhances bone metastasis and ADAM10 expression. We hypothesize that increased RANKL cleavage by ADAM 10 allows RANKL to bind its receptors expressed on nearby osteoclasts further perpetuating the vicious cycle of bone metastasis. These data suggest that bone metastasis may be controlled by inhibiting ADAM10 activity to reduce RANKL induced osteolysis and tumor progression. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1156.
Blood Pressure, Cholesterol Guidelines Face More Delays
Authors: Mike Mitka
Journal: JAMA (2013)

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