tbuckley/cabot-search huggingface dataset:
Dysregulation of Arousal and Amygdala-Prefrontal Systems in Paranoid Schizophrenia
Authors: Leanne M. Williams, Pritha Das, Anthony W.F. Harris, Belinda B. Liddell, Michael J. Brammer, Gloria Olivieri, David Skerrett, Mary L. Phillips, Anthony S. David, Anthony Peduto, Evian Gordon
Journal: American Journal of Psychiatry (2004)

The authors investigated impaired differentiation of limbic-prefrontal systems by autonomic arousal in schizophrenia. It was predicted that paranoid patients would be distinguished by a disjunction of hyperarousal but reduced amygdala and medial prefrontal activity relative to both healthy comparison subjects and patients with nonparanoid schizophrenia.Pictures depicting facial expressions of fear were presented to 27 schizophrenia patients (13 paranoid, 14 nonparanoid) and 22 matched healthy comparison subjects in an implicit perception task to evoke limbic activity. Simultaneous functional magnetic resonance imaging and skin conductance arousal recordings were acquired during presentation of faces expressing fear or neutral emotion. Responses to fear stimuli were further examined by contrasting those that were associated with a skin conductance response ("with arousal") and those that were not ("without arousal").In the comparison subjects, arousal dissociated amygdala/medial prefrontal ("visceral") networks and hippocampus/lateral prefrontal ("context") networks for fear perception. Excessive arousal responses were elicited in the schizophrenia subjects, but there was an associated reduction in amygdala/medial prefrontal activity. This disjunction was pronounced in paranoid patients relative to both healthy subjects and nonparanoid patients. Paranoid patients also showed a relatively greater prefrontal deficit for "without-arousal" responses.This is the first study to reveal a functional disconnection in autonomic and central systems for processing threat-related signals in patients with paranoid schizophrenia. Paranoid cognition may reflect an internally generated cycle of misattribution regarding incoming fear signals due to a breakdown in the regulation of these systems.
The anti-aging gene KLOTHO is a novel target for epigenetic silencing in human cervical carcinoma
Authors: Jaehyouk Lee, Dong-Jun Jeong, Jinsun Kim, Soonduck Lee, Jin-Hwa Park, Boogi Chang, Sam-Il Jung, Lisha Yi, Youngsoo Han, Young Yang, Keun Kim, Jong-Seok Lim, Inchul Yang, Seob Jeon, Dong Bae, Chang-Jin Kim, Myeong-Sok Lee
Journal: Molecular Cancer (2010)

Klotho was originally characterized as an anti-aging gene that predisposed Klotho-deficient mice to a premature aging-like syndrome. Recently, KLOTHO was reported to function as a secreted Wnt antagonist and as a tumor suppressor. Epigenetic gene silencing of secreted Wnt antagonists is considered a common event in a wide range of human malignancies. Abnormal activation of the canonical Wnt pathway due to epigenetic deregulation of Wnt antagonists is thought to play a crucial role in cervical tumorigenesis. In this study, we examined epigenetic silencing of KLOTHO in human cervical carcinoma.Loss of KLOTHO mRNA was observed in several cervical cancer cell lines and in invasive carcinoma samples, but not during the early, preinvasive phase of primary cervical tumorigenesis. KLOTHO mRNA was restored after treatment with either the DNA demethylating agent 2'-deoxy-5-azacytidine or histone deacetylase inhibitor trichostatin A. Methylation-specific PCR and bisulfite genomic sequencing analysis of the promoter region of KLOTHO revealed CpG hypermethylation in non-KLOTHO-expressing cervical cancer cell lines and in 41% (9/22) of invasive carcinoma cases. Histone deacetylation was also found to be the major epigenetic silencing mechanism for KLOTHO in the SiHa cell line. Ectopic expression of the secreted form of KLOTHO restored anti-Wnt signaling and anti-clonogenic activity in the CaSki cell line including decreased active beta-catenin levels, suppression of T-cell factor/beta-catenin target genes, such as c-MYC and CCND1, and inhibition of colony growth.Epigenetic silencing of KLOTHO may occur during the late phase of cervical tumorigenesis, and consequent functional loss of KLOTHO as the secreted Wnt antagonist may contribute to aberrant activation of the canonical Wnt pathway in cervical carcinoma.
Promyelocytic leukemia (PML) gene expression is a prognostic factor in ampullary cancer patients
Authors: B. Vincenzi, D. Santini, G. Perrone, A. Russo, V. Adamo, S. Rizzo, F. Castri, A. Antinori, R. Alloni, P.F. Crucitti, S. Morini, C. Rabitti, F.M. Vecchio, P. Magistrelli, R. Coppola, G. Tonini
Journal: Annals of Oncology (2008)
Dynamic Responses of the Right Ventricle following Extensive Damage by Cauterization
Authors: ABRAHAM KAGAN
Journal: Circulation (1952)

Previous observations that major destruction of the right ventricular walls causes but slight changes in venous and arterial pressures were confirmed. Furthermore, additional observations indicated that the compensatory reaction of the damaged ventricle to stress is diminished surprisingly little. The results are considered evidence that the cauterization procedure and others of a similar nature do not produce right heart failure and, therefore, would not be expected to cause venous congestion. The subsidiary muscular mechanism which maintains the right ventricular pump remains enigmatic; but evidence is submitted that the damaged right ventricle is regulated independently of the left.
Virtual skin biopsy by optical coherence tomography: the first quantitative imaging biomarker for scleroderma
Authors: Giuseppina Abignano, Sibel Zehra Aydin, Concepción Castillo-Gallego, Vasiliki Liakouli, Daniel Woods, Adam Meekings, Richard J Wakefield, Dennis G McGonagle, Paul Emery, Francesco Del Galdo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Skin involvement is of major prognostic value in systemic sclerosis (SSc) and often the primary outcome in clinical trials. Nevertheless, an objective, validated biomarker of skin fibrosis is lacking. Optical coherence tomography (OCT) is an imaging technology providing high-contrast images with 4 μm resolution, comparable with microscopy ('virtual biopsy'). The present study evaluated OCT to detect and quantify skin fibrosis in SSc. <h3>Methods</h3> We performed 458 OCT scans of hands and forearms on 21 SSc patients and 22 healthy controls. We compared the findings with histology from three skin biopsies and by correlation with clinical assessment of the skin. We calculated the optical density (OD) of the OCT images employing Matlab software and performed statistical analysis of the results, including intraobserver/interobserver reliability, employing SPSS software. <h3>Results</h3> Comparison of OCT images with skin histology indicated a progressive loss of visualisation of the dermal–epidermal junction associated with dermal fibrosis. Furthermore, SSc affected skin showed a consistent decrease of OD in the papillary dermis, progressively worse in patients with worse modified Rodnan skin score (p&lt;0.0001). Additionally, clinically unaffected skin was also distinguishable from healthy skin for its specific pattern of OD decrease in the reticular dermis (p&lt;0.001). The technique showed an excellent intraobserver and interobserver reliability (intraclass correlation coefficient &gt;0.8). <h3>Conclusions</h3> OCT of the skin could offer a feasible and reliable quantitative outcome measure in SSc. Studies determining OCT sensitivity to change over time and its role in defining skin vasculopathy may pave the way to defining OCT as a valuable imaging biomarker in SSc.
Intussusception in a Case of Penetrating Abdominal Injury
Authors: H. S. K. Singha
Journal: BMJ (1958)

The patient's hospital menu was then examined, and this showed that chicken had been included in the diet on three occasions, twice after the dental extraction and once the day following the pseudarthrosis.It would seem most probable that the offending bone was swallowed on the last occasion, since this was rapidly followed by vomiting and then a haematemesis.
Efficacy and Safety of Troglitazone in the Treatment of Lipodystrophy Syndromes
Authors: Elif Arioglu, Jennifer Duncan-Morin, Nancy Sebring, Kristina I. Rother, Nicole Gottlieb, Jay Lieberman, David Herion, David E. Kleiner, James Reynolds, Ahalya Premkumar, Anne E. Sumner, Jay Hoofnagle, Marc L. Reitman, Simeon I. Taylor
Journal: Annals of Internal Medicine (2000)

Background: Troglitazone promotes adipocyte differentiation in vitro and increases insulin sensitivity in vivo. Therefore, troglitazone may have therapeutic benefit in lipoatrophic diabetes. Objective: To determine whether troglitazone ameliorates hyperglycemia and hypertriglyceridemia or increases fat mass in lipoatrophic patients. Design: Open-labeled prospective study. Setting: United States and Canada. Patients: 20 patients with various syndromes associated with lipoatrophy or lipodystrophy. Intervention: 6 months of therapy with troglitazone, 200 to 600 mg/d. Measurements: Levels of hemoglobin A1c, triglycerides, free fatty acids, and insulin; respiratory quotient; percentage of body fat; liver volume; and regional fat mass. Results: In the 13 patients with diabetes who completed 6 months of troglitazone therapy, hemoglobin A1c levels decreased by a mean of 2.8% (95% CI, 1.9% to 3.7%; P < 0.001). In all 19 study patients, fasting triglyceride levels decreased by 2.6 mmol/L (230 mg/dL) (CI, 0.7 to 4.5 mmol/L [62 to 398 mg/dL]; P = 0.019) and free fatty acid levels decreased by 325 µmol/L (CI, 135 to 515 µmol/L; P = 0.035). The respiratory quotient decreased by a mean of 0.12 (CI, 0.08 to 0.16; P < 0.001), suggesting that troglitazone promoted oxidation of fat. Body fat increased by a mean of 2.4 percentage points (CI, 1.3 to 4.5 percentage points; P = 0.044). Magnetic resonance imaging showed an increase in subcutaneous adipose tissue but not in visceral fat. In one patient, the serum alanine aminotransferase level increased eightfold during the 10th months of troglitazone treatment but normalized 3 months after discontinuation of treatment. Liver biopsy revealed an eosinophilic infiltrate, suggesting hypersensitivity reaction as a cause of hepatotoxicity. Conclusion: Troglitazone therapy improved metabolic control and increased body fat in patients with lipoatrophic diabetes. The substantial benefits of troglitazone must be balanced against the risk for hepatotoxicity, which can occur relatively late in the treatment course.
Cyclosporine and posttransplant hypertension.
Authors: J J Curtis
Journal: Journal of the American Society of Nephrology (1992)

Prevalence studies suggest that hypertension is present in more than 50% of kidney transplant patients. It is more prevalent in pediatric patients, and cyclosporine has added to the rates in both children and adults. Hypertension is an important risk factor for cardiovascular disease, which remains the leading cause of death for recipients of renal transplants. Fortunately, posttransplant hypertension is commonly mild to moderate in nature (transplant artery stenosis hypertension being the exception) and can be treated medically. However, the removal of native kidneys and the correction of arterial stenosis are two surgical interventions that are more common in the transplant population than in the general population. In posttransplant hypertension that is primarily due to cyclosporine, one must balance the risks of reduced cyclosporine dosage against the risks of the hypertension. Both diuretic and calcium channel blocker therapy are believed to be useful in cyclosporine-induced hypertension. Other vasodilators also may be effective, although they may have undesired effects on RBF and glomerular filtration.
Retroposon Insertions and the Chronology of Avian Sex Chromosome Evolution
Authors: Alexander Suh, Jan Ole Kriegs, Jürgen Brosius, Jürgen Schmitz
Journal: Molecular Biology and Evolution (2011)

The vast majority of extant birds possess highly differentiated Z and W sex chromosomes. Nucleotide sequence data from gametologs (homologs on opposite sex chromosomes) suggest that this divergence occurred throughout early bird evolution via stepwise cessation of recombination between identical sex chromosomal regions. Here, we investigated avian sex chromosome differentiation from a novel perspective, using retroposon insertions and random insertions/deletions for the reconstruction of gametologous gene trees. Our data confirm that the CHD1Z/CHD1W genes differentiated in the ancestor of the neognaths, whereas the NIPBLZ/NIPBLW genes diverged in the neoavian ancestor and independently within Galloanserae. The divergence of the ATP5A1Z/ATP5A1W genes in galloanserans occurred independently in the chicken, the screamer, and the ancestor of duck-related birds. In Neoaves, this gene pair differentiated in each of the six sampled representatives, respectively. Additionally, three of our investigated loci can be utilized as universal, easy-to-use independent tools for molecular sexing of Neoaves or Neognathae.
Five-lipoxygenase products in glomerular immune injury.
Authors: K F Badr
Journal: Journal of the American Society of Nephrology (1992)

Leukocyte infiltration, proliferation, and activation are central pathogenetic components of immune injury in the glomerulus. Initial cellular infiltration by polymorphonuclear leukocytes (PMN) is a consequence of the deposition of immune complexes at discreet sites in the glomerulus. This is often followed by macrophage/monocyte infiltration, as well as proliferation of resident mesangial macrophages. Activated leukocytes constitute a rich source of lipid-derived bioactive autacoids, in particular, oxygenated metabolites of arachidonic acid. Here, we assess the role of the five-lipoxygenase (5-LO) family of eicosanoids, in particular, leukotrienes D4 and B4 (LTD4 and LTB4) in mediating functional and structural deterioration during immune inflammatory reactions in the glomerulus. LTD4 and other peptidyl LT appear to play a central role in the reductions in GFR in the acute phases of injury by virtue of their potent vasoactive properties, in particular, their capacity to reduce the glomerular capillary ultrafiltration coefficient, likely through contraction of smooth muscle elements in glomerular mesangial cells. The latter cells possess specific receptors for LTD4 in both humans and rat and contract in vitro when exposed to LTD4 after receptor-mediated activation of phospholipase C. LTB4, a nonvasoconstrictor LT, is released in the early phases of immune injury, likely from leukocyte sources as well as from transcellular metabolism of its precursor, LTA4, by the enzyme LTA4-hydrolase in glomerular mesangial and endothelial cells. LTB4, a potent promoter of PMN attraction, adhesion, and activation exacerbates glomerular functional impairment and structural damage by amplifying PMN-dependent mechanisms of injury. In their totality, 5-LO products of arachidonic acid contribute to the impairment of the normal glomerular filtration and sieving functions that attend acute inflammatory injury in the renal glomerulus and to the subsequent progression of glomerular destruction. This is high-lighted by the significant degree of protection afforded by the selective inhibition of arachidonate 5-LO in vivo in acute and chronic models of experimental glomerulonephritis.
In vitro comparison of the effect of inhalation delay on the variability of the delivered dose from valved holding chambers
Authors: Dirk Von Hollen, Paul Hancock, Ross Hatley, Kurt Nikander
Journal: European Respiratory Journal (2012)

The valved holding chamber (VHC) has been designed to optimize delivery for those using pressurized metered dose inhalers (pMDIs). We tested the effects on delivered dose of increasing delay between pMDI actuation and flow through the VHC, using both anti-static and conventional VHCs.  Ten anti-static Diamond (Diamond; Philips Respironics) VHCs, anti-static AeroChamber Plus Z-Stat and conventional AeroChamber Plus (Z-stat and AC Plus; Monaghan Medical Corp.) VHCs were washed and air dried and six HFA albuterol sulfate pMDIs (ProAir HFA, 90 µg albuterol, Teva Specialty Pharmaceuticals LLC) were primed before use. For each run the pMDI was actuated into the VHC, after a delay of 0, 5 or 10 s flow through the VHC and attached filter occurred at an extraction flow rate of 5, 15 or 30 L/min for 10 s. The pMDI was actuated 10 times for each of the 10 VHCs of each brand at each delay/flow rate combination. Drug deposits were analyzed using HPLC. Results are presented as coefficient of variation of the delivered doses.  The co-efficient of variation was highest for the conventional VHC for all test conditions. Use of an anti-static VHC can minimize variability (improve reproducibility) in delivered dose under in vitro test conditions.
Altered Subcellular Localization of Tumor-Specific Cyclin E Isoforms Affects Cyclin-Dependent Kinase 2 Complex Formation and Proteasomal Regulation
Authors: Nikki A. Delk, Kelly K. Hunt, Khandan Keyomarsi
Journal: Cancer Research (2009)

Abstract In tumors, alternative translation and posttranslational proteolytic cleavage of full-length cyclin E (EL) produces tumorigenic low molecular weight cyclin E (LMW-E) isoforms that lack a portion of the EL amino-terminus containing a nuclear localization sequence. Therefore, we hypothesized that LMW-E isoforms have altered subcellular localization. To explore our hypothesis, we compared EL versus LMW-E localization in cell lysates and in vivo using fractionation and protein complementation assays. Our results reveal that LMW-E isoforms preferentially accumulate in the cytoplasm where they bind the cyclin E kinase partner, cyclin-dependent kinase 2 (Cdk2), and have associated kinase activity. The nuclear ubiquitin ligase Fbw7 targets Cdk2-bound cyclin E for degradation; thus, we examined if altered subcellular localization affected LMW-E degradation. We found that cytoplasmic LMW-E/Cdk2 was less susceptible to Fbw7-mediated degradation. One implication of our findings is that altered LMW-E and LMW-E/Cdk2 subcellular localization may lead to aberrant LMW-E protein interactions, regulation, and activity, ultimately contributing to LMW-E tumorigenicity. [Cancer Res 2009;69(7):2817–25]
Combined antagonism of leukotrienes and histamine produces predominant inhibition of allergen-induced early and late phase airway obstruction in asthmatics.
Authors: A Roquet, B Dahlén, M Kumlin, E Ihre, G Anstrén, S Binks, S E Dahlén
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We defined the contribution of histamine and leukotrienes to allergen-induced airway obstruction in asthmatics; 12 subjects with allergic asthma underwent identical allergen bronchoprovocations on four occasions. At a control session, all subjects displayed early (EAR) and late asthmatic (LAR) reactions. The mean (+/- SE) drop in FEV1 during EAR (0-2 h) and LAR (2-12 h) was 29 +/- 2% and 28 +/- 4%, respectively. Thereafter, the influence of 1 wk randomized pretreatment with the leukotriene receptor antagonist zafirlukast (Accolate) (80 mg twice daily), the antihistamine loratadine (10 mg twice daily), and the combination of both antagonists was assessed. Expressed as AUC FEV1 in percent of the control reaction, zafirlukast reduced the response during EAR and LAR by 62 +/- 11% and 55 +/- 12%, respectively (p < 0.05 versus control). Loratadine inhibited EAR and LAR by 25 +/- 14% and 40 +/- 16%, respectively (p < 0.05 versus control). Zafirlukast was significantly more effective than loratadine during EAR but not during LAR. The combination of zafirlukast and loratadine reduced the AUC FEV1 during EAR and LAR further, by 75 +/- 8% and 74 +/- 14%, respectively (p < 0.05 versus control). The combination was significantly (p < 0.05) more effective than either drug alone during the LAR. The findings indicate that leukotrienes and histamine together mediate the major part of both the EAR and the LAR following exposure of asthmatics to allergen. Combination of leukotriene antagonism and antihistamines may represent a new strategy for treatment of airway obstruction in asthma.
Tumor Cavitation: Impact on Objective Response Evaluation in Trials of Angiogenesis Inhibitors in Non–Small-Cell Lung Cancer
Authors: Simon J. Crabb, Demetris Patsios, Eric Sauerbrei, Peter M. Ellis, Andrew Arnold, Glenwood Goss, Natasha B. Leighl, Frances A. Shepherd, Jean Powers, Lesley Seymour, Scott A. Laurie
Journal: Journal of Clinical Oncology (2008)

We have observed cavitation of lesions in clinical trials of an angiogenesis inhibitor combined with chemotherapy for non-small-cell lung cancer (NSCLC). We hypothesized that cavitation might alter response assessment in such clinical trials.We performed a retrospective radiologic review of patients with NSCLC enrolled onto three National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trials of platinum-based chemotherapy with or without a small-molecule angiogenesis inhibitor (vascular endothelial growth factor receptor inhibitor [VEGFRI]). Response was assessed both by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines and a novel alternate method in which the longest diameter of any cavity was subtracted from the overall longest diameter of that lesion to measure target lesions. Rates of cavitation were documented.Marked cavitation of pulmonary lesions was seen in 24% of 33 patients treated with VEGFRI combined with platinum-based chemotherapy but in none of 18 patients treated with platinum-based chemotherapy alone. Use of the alternate method for response assessment resulted in an alteration of response assessment, time to best response, duration of response, and time of disease progression in a minority of patients compared with RECIST.Cavitation of target and nontarget lesions is common in NSCLC patients treated with VEGFRIs and platinum-based chemotherapy. Impact on response and time to event outcomes occurred but seems to be less common. Response assessment might be improved by incorporating cavitation into volume assessment for target lesions, potentially altering outcomes of key efficacy parameters in clinical trials. This should be prospectively assessed in clinical trials of angiogenesis inhibitors.
The Elmer Belt Library of Vinciana
Authors: C. Donald O'Malley
Journal: JAMA (1967)

In May 1966 an international symposium on Leonardo da Vinci was held at the University of California, Los Angeles, in which nine major authorities from five different nations presented lectures on some of the widely diverse facets of Leonardo's extraordinary life and activities. The proceedings are scheduled for publication in the autumn of 1967. The occasion for the symposium was the celebration marking the opening of the University's new Dickson Art Center. However, the subject of the symposium was a recognition of Dr. Elmer Belt's generous donation of his great Leonardo collection; the formal opening of this collection as the Elmer Belt Library of Vinciana coincided with the proceedings. As one member of the symposium remarked concerning the significance of the gift, "Possibly the British Museum or the Library of Congress contains, scattered throughout the immensity of its shelves, most of the volumes in the Belt collection. But nowhere else
Multiple osteochondroses and avulsion fracture of anterior superior iliac spine in a soccer player
Authors: M N Doral, S T Aydog, O Tetik, O A Atay, E Turhan, H A Demirel
Journal: British Journal of Sports Medicine (2005)

Apophysitis describes a chronic traction injury at the insertion site of a tendon. There is a gradual onset of pain with no clear history of injury. Without adequate preventive methods, an avulsion fracture may result. The case is here reported of an apophyseal avulsion fracture of the anterior superior iliac spine in an adolescent caused by playing football before the end of treatment for apophysitis. An open reduction and internal fixation was performed followed by a rehabilitation programme. No complications occurred, and the patient had returned to his previous level of sporting activity after six weeks.