tbuckley/cabot-search huggingface dataset:
Selective Downregulation of VEGF-A <sub>165</sub> , VEGF-R <sub>1</sub> , and Decreased Capillary Density in Patients With Dilative but Not Ischemic Cardiomyopathy
Authors: Dietmar Abraham, Reinhold Hofbauer, Romana Schäfer, Roland Blumer, Patrick Paulus, Aurelia Miksovsky, Hannes Traxler, Alfred Kocher, Seyedhossein Aharinejad
Journal: Circulation Research (2000)

Cardiomyopathy (CM) comprises a heterogeneous group of diseases, including ischemic (ICM) and dilative (DCM) forms. The pathogenesis of primary DCM is not clearly understood. Recent studies in mice show that vascular endothelial growth factor (VEGF) is involved in ICM. Whether VEGF plays a role in human CM is unknown. We examined the mRNA and protein expression of VEGF and its receptors in hearts of patients with end-stage DCM and ICM and in healthy individuals using real-time polymerase chain reaction and Western blotting. Number of capillaries, area of myocytes, and collagen were calculated in cardiac biopsies using transmission electron microscopy. In DCM, except for VEGF-C, mRNA transcript levels of VEGF-A(165), VEGF-A(189), and VEGF-B and the protein level of VEGF-A and VEGF-R(1) were downregulated compared with controls (P:<0.05). However, in ICM, mRNA transcript levels of VEGF isoforms and protein levels of VEGF-C were upregulated. The vascular density was decreased in DCM but increased in ICM compared with controls (P:<0. 05). Muscular hypertrophy was not different for ICM and DCM, although DCM had more collagen (P:<0.05). Blunted VEGF-A and VEGF-R(1) protein expression and downregulated mRNA of the predominant isoform of VEGF-A, VEGF-A(165), to our knowledge shown here for the first time, provide evidence that the VEGF-A defect in DCM is located upstream. Whether downregulation of certain VEGF isoforms in DCM is a cause or consequence of this disorder remains unclear, although upregulated VEGF levels in ICM are most likely the result of ischemia.
Patients with xeroderma pigmentosum complementation groups C, E and V do not have abnormal sunburn reactions
Authors: M. Sethi, A.R. Lehmann, H. Fawcett, M. Stefanini, N. Jaspers, K. Mullard, S. Turner, A. Robson, D. McGibbon, R. Sarkany, H. Fassihi
Journal: British Journal of Dermatology (2013)

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of DNA repair. It is divided into eight complementation groups: XP‐A to XP‐G (classical XP) and XP variant (XP‐V). Severe and prolonged sunburn reactions on minimal sun exposure have been considered a cardinal feature of classical XP. However, it has recently become clear that not all patients have abnormal sunburn reactions. To examine sunburn reactions in a cohort of patients with XP and correlate this to the complementation group. Sixty patients with XP attending the U.K. National XP Service from 2010 to 2012 were studied. Their history of burning after minimal sun exposure was assessed using a newly developed sunburn severity score. The age at which the first skin cancer was histologically diagnosed in each patient, and the presence of any neurological abnormality, was also recorded. Sunburn severity scores were abnormally high in patients with XP‐A, XP‐D, XP‐F and XP‐G compared with non‐XP controls. There was no significant difference in sunburn score of patients with XP‐C, XP‐E and XP‐V compared with controls (P > 0·05). Patients with XP‐C, XP‐E and XP‐V were more likely to have skin cancer diagnosed at an earlier age than those with severe sunburn on minimal sun exposure. In addition, patients with XP with severe sunburn had an increased frequency of neurological abnormalities. Not all patients with XP have a history of severe and prolonged sunburn on minimal sun exposure. The normal sunburn response of patients with XP‐C, XP‐E and XP‐V may relate to the preservation of transcription‐coupled DNA repair in these groups. Those with a history of severe sunburn on minimal sun exposure developed their first skin cancer at an older age compared with patients with XP‐C, XP‐E and XP‐V, but they had an increased frequency of neurological abnormalities. Physicians need to be aware that about half of all patients with XP will present without a history of abnormal sunburn.
P812 NOX2-GENERATED OXIDATIVE STRESS IS INCREASED IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE INDEPENDENTLY FROM METABOLIC SYNDROME
Authors: M. Del Ben, L. Polimeni, R. Carnevale, S. Bartimoccia, F. Baratta, D. Pastori, C. Calabrese, D. Salzano, F. Angelico
Journal: Journal of Hepatology (2014)
Intercellular adhesion molecules (ICAMs) and spermatogenesis
Authors: Xiang Xiao, Dolores D. Mruk, C. Yan Cheng
Journal: Human Reproduction Update (2013)

BACKGROUNDDuring the seminiferous epithelial cycle, restructuring takes places at the Sertoli–Sertoli and Sertoli–germ cell interface to accommodate spermatogonia/spermatogonial stem cell renewal via mitosis, cell cycle progression and meiosis, spermiogenesis and spermiation since developing germ cells, in particular spermatids, move 'up and down' the seminiferous epithelium. Furthermore, preleptotene spermatocytes differentiated from type B spermatogonia residing at the basal compartment must traverse the blood–testis barrier (BTB) to enter the adluminal compartment to prepare for meiosis at Stage VIII of the epithelial cycle, a process also accompanied by the release of sperm at spermiation. These cellular events that take place at the opposite ends of the epithelium are co-ordinated by a functional axis designated the apical ectoplasmic specialization (ES)—BTB—basement membrane. However, the regulatory molecules that co-ordinate cellular events in this axis are not known.
Care Patterns in Medicare and Their Implications for Pay for Performance
Authors: Hoangmai H. Pham, Deborah Schrag, Ann S. O'Malley, Beny Wu, Peter B. Bach
Journal: New England Journal of Medicine (2007)

Two assumptions underpin the implementation of pay for performance in Medicare: that with the use of claims data, patients can be assigned to a physician or to a practice that will have primary responsibility for their care, and that a meaningful fraction of the care physicians deliver is for patients for whom they have primary responsibility.
Glycyrrhetinic acid-modified chitosan/poly(ethylene glycol) nanoparticles for liver-targeted delivery
Authors: Qin Tian, Chuang-Nian Zhang, Xiu-Hua Wang, Wei Wang, Wei Huang, Rui-Tao Cha, Chun-Hong Wang, Zhi Yuan, Min Liu, Hai-Ying Wan, Hua Tang
Journal: Biomaterials (2010)
Collateral damage from oral ciprofloxacin versus nitrofurantoin in outpatients with urinary tract infections: a culture-free analysis of gut microbiota
Authors: A.J. Stewardson, N. Gaïa, P. François, S. Malhotra-Kumar, C. Delémont, B. Martinez de Tejada, J. Schrenzel, S. Harbarth, V. Lazarevic
Journal: Clinical Microbiology and Infection (2014)
EphB4 Expression and Biological Significance in Prostate Cancer
Authors: Guangbin Xia, S. Ram Kumar, Rizwan Masood, Sutao Zhu, Ramchandra Reddy, Valery Krasnoperov, David I. Quinn, Susan M. Henshall, Robert L. Sutherland, Jacek K. Pinski, Siamak Daneshmand, Maurizio Buscarini, John P. Stein, Chen Zhong, Daniel Broek, Pradip Roy-Burman, Parkash S. Gill
Journal: Cancer Research (2005)

Abstract Prostate cancer is the most common cancer in men. Advanced prostate cancer spreading beyond the gland is incurable. Identifying factors that regulate the spread of tumor into the regional nodes and distant sites would guide the development of novel diagnostic, prognostic, and therapeutic targets. The aim of our study was to examine the expression and biological role of EphB4 in prostate cancer. EphB4 mRNA is expressed in 64 of 72 (89%) prostate tumor tissues assessed. EphB4 protein expression is found in the majority (41 of 62, 66%) of tumors, and 3 of 20 (15%) normal prostate tissues. Little or no expression was observed in benign prostate epithelial cell line, but EphB4 was expressed in all prostate cancer cell lines to varying degrees. EphB4 protein levels are high in the PC3 prostate cancer cell line and several folds higher in a metastatic clone of PC3 (PC3M) where overexpression was accompanied by EphB4 gene amplification. EphB4 expression is induced by loss of PTEN, p53, and induced by epidermal growth factor/epidermal growth factor receptor and insulin-like growth factor-I/insulin-like growth factor-IR. Knockdown of the EphB4 protein using EphB4 short interfering RNA or antisense oligodeoxynucleotide significantly inhibits cell growth/viability, migration, and invasion, and induces apoptosis in prostate cancer cell lines. Antisense oligodeoxynucleotide targeting EphB4 in vivo showed antitumor activity in murine human tumor xenograft model. These data show a role for EphB4 in prostate cancer and provide a rationale to study EphB4 for diagnostic, prognostic, and therapeutic applications.
Diabetes With the 3243 Mitochondrial tRNALeu(UUR) Mutation: Characteristic neuroimaging findings
Authors: Yoshihiko Suzuki, Takashi Hata, Hitoshi Miyaoka, Yoshito Atsumi, Hiroko Kadowaki, Matsuo Taniyama, Takasi Kadowaki, Masato Odawara, Yasushi Tanaka, Takayuki Asahina, Kempei Matsuoka
Journal: Diabetes Care (1996)

OBJECTIVE To investigate the basis of central nervous system dysfunction in diabetes associated with the 3243 mitochondrial tRNA mutation, we studied neuroimaging findings in patients with this disease. RESEARCH DESIGN AND METHODS We screened 205 diabetic patients. Those patients who had the 3243 mutation in leukocytes or muscle were enrolled. All the subjects underwent computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and N-isopropyl-p-[123I]iodoamphetamine ([123I]IMP) single-photon emission computed tomography (SPECT) of the brain. RESULTS None of the nine subjects with the 3243 mutation had the typical clinical picture of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, and none had neurological focal signs. CT or MRI revealed diffuse brain atrophy in three patients (33%) and cerebellar atrophy in one (11%). Abnormal high intensity areas were observed on MRI in five patients (56%). The overall prevalence of brain abnormalities was 56% (5 of 9) on CT and 78% (7 of 9) on MRI scans. MRA revealed no stenotic lesions. SPECT showed reduced accumulation of [123I]IMP in the right or left parieto-occipital region in eight patients (89%). CONCLUSIONS Reduced accumulation of [123I]IMP in the parieto-occipital cortex was found in a high proportion of our subjects on SPECT. This imaging finding might be characteristic of diabetes associated with the 3243 mitochondrial tRNA mutation and may be a sign of latent central nervous system dysfunction.
Long-term multicentre randomised controlled study of high frequency chest wall oscillation versus positive expiratory pressure mask in cystic fibrosis
Authors: Maggie Patricia McIlwaine, Nancy Alarie, George F Davidson, Larry C Lands, Felix Ratjen, Ruth Milner, Blythe Owen, Jennifer L Agnew
Journal: Thorax (2013)

<h3>Background</h3> Positive expiratory pressure (PEP) is the most commonly used method of airway clearance (AC) in Canada for patients with cystic fibrosis (CF) whereas, in some countries, high frequency chest wall oscillation (HFCWO) is the preferred form of AC. There have been no long-term studies comparing the efficacy of HFCWO and PEP in the CF population. <h3>Objectives</h3> To determine the long-term efficacy of HFCWO compared with PEP mask therapy in the treatment of CF as measured by the number of pulmonary exacerbations (PEs). <h3>Methods</h3> A randomised controlled study was performed in 12 CF centres in Canada. After a 2-month washout period, subjects were randomised to perform either HFCWO or PEP mask therapy for 1 year. <h3>Results</h3> 107 subjects were enrolled in the study; 51 were randomised to PEP and 56 to HFCWO. There were 19 dropouts within the study period, of which 16 occurred prior to or at the time of randomisation. There were significant differences between the groups in the mean number of PEs (1.14 for PEP vs 2.0 for HFCWO) and time to first PE (220 days for PEP vs 115 days for HFCWO, p=0.02). There was no significant difference in lung function, health-related quality of life scores or patient satisfaction scores between the two groups. PEP mask therapy required a shorter treatment time. <h3>Conclusions</h3> The results of this study favour PEP and do not support the use of HFCWO as the primary form of AC in patients with CF. <h3>Clinical Trial Registration number</h3> NCT00817180.
C reactive protein and prealbumin as markers of disease activity in shigellosis.
Authors: W A Khan, M A Salam, M L Bennish
Journal: Gut (1995)

To evaluate serum C reactive protein (CRP) and prealbumin concentrations as markers of disease activity in shigellosis this study serially measured serum concentrations of CRP and prealbumin in 39 patients infected with Shigella spp, and a comparison group of 10 patients infected with Vibrio cholerae serotype 01. On admission, patients with shigellosis had significantly higher median concentrations of CRP (109 v 5 mg/l; p &lt; 0.01) and significantly lower median concentrations of prealbumin (16 v 23 mg/l; p &lt; 0.01) than did patient with cholera. Among Shigella spp infected patients, CRP concentrations were significantly lower, and prealbumin concentrations significantly higher, on study days 3 and 5 when compared with admission values. Among Shigella spp infected patients, those in whom treatment failed had higher admission CRP concentrations than those in whom treatment was successful (p = 0.142). An admission CRP concentration &gt; or = 110 mg/l had a 70% sensitivity and a 61% specificity in predicting failure of treatment among patients infected with Shigella spp; the predictive value of a positive and negative test was 14% and 96% respectively. In summary, acute shigellosis elicits an acute phase response, the magnitude of which predicts clinical outcome.
Does laparoscopic surgery spell the end of the open surgeon?
Authors: R. Agha, G. Muir
Journal: Journal of the Royal Society of Medicine (2003)

Barely fifteen years have passed since the laparoscopic era was launched with a cholecystectomy by the French surgeon Philippe Mouret.1 Yet today by far the majority of cholecystectomies are done in this way,2 and laparoscopic surgery finds many other indications. The UK has been slower than some other countries to adopt these techniques; indeed, the President of the Association of Coloproctology, Neil Mortensen, has declared ‘... it is scandalous how far we are behind on keyhole surgery for bowel cancer and other bowel problems’ (Daily Telegraph, 6 May 2003).

The range of operations now extends from simple procedures such as herniorrhaphy and ovarian cystectomy to complex operations including radical prostatectomy, nephrectomy, and adrenalectomy.3 Where will this end? Do such techniques spell the demise of open surgery? In discussing this matter we confine ourselves to laparoscopy, though the argument applies also to numerous other procedures whereby open operation is replaced by use of small incisions and long thin instruments, with display of the surgical field on a monitor.

The question in our title requires analysis of two key elements: is laparoscopic surgery better for the patient (without unduly hampering the surgeon); and is it practically and financially feasible?
Potential mechanisms of prospective antimigraine drugs: A focus on vascular (side) effects
Authors: Kayi Y. Chan, Steve Vermeersch, Jan de Hoon, Carlos M. Villalón, Antoinette MaassenVanDenBrink
Journal: Pharmacology & Therapeutics (2010)

Currently available drugs for the acute treatment of migraine, i.e. ergot alkaloids and triptans, are cranial vasoconstrictors. Although cranial vasoconstriction is likely to mediate-at least a part of-their therapeutic effects, this property also causes vascular side-effects. Indeed, the ergot alkaloids and the triptans have been reported to induce myocardial ischemia and stroke, albeit in extremely rare cases, and are contraindicated in patients with known cardiovascular risk factors. In view of these limitations, novel antimigraine drugs devoid of vascular (side) effects are being explored. Currently, calcitonin gene-related peptide (CGRP) receptor antagonists, which do not have direct vasoconstrictor effects, are under clinical development. Other classes of drugs, such as 5-HT(1F) receptor agonists, glutamate receptor antagonists, nitric oxide synthase inhibitors, VPAC/PAC receptor antagonists and gap junction modulators, have also been proposed as potential targets for acute antimigraine drugs. Although these prospective drugs do not directly induce vasoconstriction, they may well induce indirect vascular effects by inhibiting or otherwise modulating the responses to endogenous vasoactive substances. These indirect vascular effects might contribute to the therapeutic efficacy of the previously mentioned compounds, but may alternatively also lead to vascular side-effects. As described in the current review, some of the prospective antimigraine drugs with a proposed non-vascular mechanism of action may still have direct or indirect vascular effects.
Does stretching increase ankle dorsiflexion range of motion? A systematic review
Authors: J A Radford, J Burns, R Buchbinder, K B Landorf, C Cook
Journal: British Journal of Sports Medicine (2006)

Background: Many lower limb disorders are related to calf muscle tightness and reduced dorsiflexion of the ankle. To treat such disorders, stretches of the calf muscles are commonly prescribed to increase available dorsiflexion of the ankle joint. Hypothesis: To determine the effect of static calf muscle stretching on ankle joint dorsiflexion range of motion. Study design: A systematic review with meta-analyses. Methods: A systematic review of randomised trials examining static calf muscle stretches compared with no stretching. Trials were identified by searching Cinahl, Embase, Medline, SportDiscus, and Central and by recursive checking of bibliographies. Data were extracted from trial publications, and meta-analyses performed that calculated a weighted mean difference (WMD) for the continuous outcome of ankle dorsiflexion. Sensitivity analyses excluded poorer quality trials. Statistical heterogeneity was assessed using the quantity I 2 . Results: Five trials met inclusion criteria and reported sufficient data on ankle dorsiflexion to be included in the meta-analyses. The meta-analyses showed that calf muscle stretching increases ankle dorsiflexion after stretching for ⩽15 minutes (WMD 2.07°; 95% confidence interval 0.86 to 3.27), &gt;15–30 minutes (WMD 3.03°; 95% confidence interval 0.31 to 5.75), and &gt;30 minutes (WMD 2.49°; 95% confidence interval 0.16 to 4.82). There was a very low to moderate statistical heterogeneity between trials. The meta-analysis results for ⩽15 minutes and &gt;15–30 minutes of stretching were considered robust when compared with sensitivity analyses that excluded lower quality trials. Conclusions: Calf muscle stretching provides a small and statistically significant increase in ankle dorsiflexion. However, it is unclear whether the change is clinically important.
Recognition of citrullinated and carbamylated proteins by human antibodies: specificity, cross-reactivity and the ‘AMC-Senshu’ method
Authors: Jing Shi, Annemiek Willemze, George M C Janssen, Peter A van Veelen, Jan Wouter Drijfhout, Anthony Cerami, Tom W J Huizinga, Leendert A Trouw, René E Toes
Journal: Annals of the Rheumatic Diseases (2012)

Recently, a novel family of autoantibodies in rheumatoid arthritis (RA) patients was described: anti-carbamylated protein (Anti-CarP) antibodies, which target carbamylated (homocitrulline-containing) epitopes.1 ,2 Since citrulline and homocitrulline have a similar structure, we wished to determine to what extent human autoantibodies can differentiate between them. Unlike human antibodies, the anti-modified citrulline (AMC) antibody developed by Dr Senshu3–8 is able to recognise citrullinated epitopes irrespective of the neighbouring amino acids. Thus, we also aimed to verify whether the AMC assay could distinguish between these two amino acids.

To address this, we loaded gels with citrullinated, carbamylated and non-modified forms of foetal calf's serum (FCS) and human fibrinogen (Fib). Gels loaded with equal amounts of these protein preparations (figure 1A) were used for western blotting and staining with the ‘AMC-Senshu’ method. Both the citrullinated and the carbamylated forms of the proteins tested were strongly recognised, whereas, the non-modified form did not reveal any staining (figure 1B). Staining similar western blots with selected human sera1 revealed that sera-positive …
Distinct KIR/HLA compound genotypes affect the kinetics of human antiviral natural killer cell responses
Authors: Golo Ahlenstiel, Maureen P. Martin, Xiaojiang Gao, Mary Carrington, Barbara Rehermann
Journal: Journal of Clinical Investigation (2008)

Genetic studies suggest a role for killer cell immunoglobulin-like receptor/HLA (KIR/HLA) compound genotypes in the outcome of viral infections, but functional data to explain these epidemiological observations have not been reported. Using an in vitro model of infection with influenza A virus (IAV), we attribute functional differences in human NK cell activity to distinct KIR/HLA genotypes. Multicolor flow cytometry revealed that the HLA-C–inhibited NK cell subset in HLA-C1 homozygous subjects was larger and responded more rapidly in IFN-γ secretion and CD107a degranulation assays than its counterpart in HLA-C2 homozygous subjects. The differential IFN-γ response was also observed at the level of bulk NK cells and was independent of KIR3DL1/HLA-Bw4 interactions. Moreover, the differential response was not caused by differences in NK cell maturation status and phenotype, nor by differences in the type I IFN response of IAV-infected accessory cells between HLA-C1 and HLA-C2 homozygous subjects. These results provide functional evidence for differential NK cell responsiveness depending on KIR/HLA genotype and may provide useful insights into differential innate immune responsiveness to viral infections such as IAV.
Evolution of HLA-B*5703 HIV-1 escape mutations in HLA-B*5703–positive individuals and their transmission recipients
Authors: Hayley Crawford, Wendy Lumm, Alasdair Leslie, Malinda Schaefer, Debrah Boeras, Julia G. Prado, Jianming Tang, Paul Farmer, Thumbi Ndung'u, Shabir Lakhi, Jill Gilmour, Paul Goepfert, Bruce D. Walker, Richard Kaslow, Joseph Mulenga, Susan Allen, Philip J.R. Goulder, Eric Hunter
Journal: The Journal of Experimental Medicine (2009)

HLA-B*57 is the class I allele most consistently associated with control of human immunodeficiency virus (HIV) replication, which may be linked to the specific HIV peptides that this allele presents to cytotoxic T lymphocytes (CTLs), and the resulting efficacy of these cellular immune responses. In two HIV C clade-infected populations in South Africa and Zambia, we sought to elucidate the role of HLA-B*5703 in HIV disease outcome. HLA-B*5703-restricted CTL responses select for escape mutations in three Gag p24 epitopes, in a predictable order. We show that the accumulation of these mutations sequentially reduces viral replicative capacity in vitro. Despite this, in vivo data demonstrate that there is ultimately an increase in viral load concomitant with evasion of all three HLA-B*5703-restricted CTL responses. In HLA-B*5703-mismatched recipients, the previously described early benefit of transmitted HLA-B*5703-associated escape mutations is abrogated by the increase in viral load coincident with reversion. Rapid disease progression is observed in HLA-matched recipients to whom mutated virus is transmitted. These data demonstrate that, although costly escape from CTL responses can progressively attenuate the virus, high viral loads develop in the absence of adequate, continued CTL responses. These data underline the need for a CTL vaccine against multiple conserved epitopes.