tbuckley/cabot-search huggingface dataset:
Wnt/β-Catenin Signaling Regulates Cytokine-Induced Human Inducible Nitric Oxide Synthase Expression by Inhibiting Nuclear Factor-κB Activation in Cancer Cells
Authors: Qiang Du, Xinglu Zhang, Jon Cardinal, Zongxian Cao, Zhong Guo, Lifang Shao, David A. Geller
Journal: Cancer Research (2009)

The human inducible nitric oxide synthase (hiNOS) gene is regulated by nuclear factor kappaB (NF-kappaB) and has recently been shown to be a target of the Wnt/beta-catenin pathway. In this study, we tested the hypothesis that Wnt/beta-catenin signaling might regulate cytokine- or tumor necrosis factor alpha (TNFalpha)-induced hiNOS expression through interaction with NF-kappaB. A cytokine mixture of TNFalpha + interleukin (IL)-1beta + IFNgamma induced a 2- to 3-fold increase in hiNOS promoter activity in HCT116 and DLD1 colon cells, but produced a 2-fold decrease in SW480 colon cancer cells. A similar differential activity was seen in liver cancer cells (HepG2, Huh7, and Hep3B). Overexpression of beta-catenin produced a dose-dependent decrease in NF-kappaB reporter activity and decreased cytokine mixture-induced hiNOS promoter activity. Gel shift for TNFalpha-induced hiNOS NF-kappaB activation showed decreased p50 binding and decreased NF-kappaB reporter activity in the beta-catenin-mutant HAbeta18 cells. Conversely, enhanced p50 binding and increased NF-kappaB reporter activity were seen in HAbeta85 cells, which lack beta-catenin signaling. Coimmunoprecipitation confirmed that beta-catenin complexed with both p65 and p50 NF-kappaB proteins. NF-kappaB-dependent Traf1 protein expression also inversely correlated with the level of beta-catenin. Furthermore, SW480 cells stably transformed with wild-type adenomatous polyposis coli showed decreased beta-catenin protein and increased TNFalpha-induced p65 NF-kappaB binding as well as iNOS and Traf1 expression. Finally, beta-catenin inversely correlated with iNOS and Fas expression in vivo in hepatocellular carcinoma tumor samples. Our in vitro and in vivo data show that beta-catenin signaling inversely correlates with cytokine-induced hiNOS and other NF-kappaB-dependent gene expression. These findings underscore the complex role of Wnt/beta-catenin, NF-kappaB, and iNOS signaling in the pathophysiology of inflammation-associated carcinogenesis.
Prevalence and possible pathological significance of calcium phosphate salt accumulation in tendon matrix degeneration.
Authors: G P Riley, R L Harrall, C R Constant, T E Cawston, B L Hazleman
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVES: To investigate the prevalence of calcium phosphate mineral salt accumulation in degenerative supraspinatus 9tendinitis9 compared with a normal sample of human tendons, and to determine whether there is an association of calcium salt deposition with pathological changes in the tendon extracellular matrix. METHODS: Cadaver tendons (supraspinatus and common biceps tendons, n = 96) and fragments of supraspinatus tendons obtained during shoulder surgery (n = 31) were analysed for calcium content by atomic absorption spectroscopy, phosphorous content using a spectrophotometric assay, and matrix composition (collagen, glycosaminoglycans and DNA) using standard biochemical techniques. RESULTS: We established baseline values of calcium concentration in macroscopically normal cadaver tendons (mean 1.1 (SD 0.35) micrograms/mg dry wt, n = 60) and found that 33% (nine of 27) of ruptured tendons from patients with 9degenerative tendinitis9 contained an excess of calcium (more than 2SD greater than the normal sample mean). Five of these specimens had increased concentrations of phosphorous and calcium:phosphorous (molar) ratios consistent with a variety of possible calcium crystals, including calcium pyrophosphate, hydroxyapatite, and tricalcium phosphate, in addition to mixed or amorphous calcium phosphate deposits. Four of these specimens contained normal concentrations of phosphorous, consistent with deposits of calcium oxalate or calcium carbonate, although this was not confirmed biochemically. In contrast, surgical specimens (n = 4) from patients with 9calcifying tendinitis9 (radiographically detected calcium deposits) all contained salts with a mineral composition consistent with hydroxyapatite. The presence and identity of crystal deposits was subsequently confirmed in five specimens by radiographic microanalysis. Analysis of the tendon matrix demonstrated a number of significant differences between normal and degenerate (ruptured) tendons, including a reduction in collagen content, an increase in sulphated glycosaminoglycans (predominantly dermatan sulphate) and an increase in DNA (cellular) content. However, there were no significant differences between degenerate tendons that were 9calcified9 and those degenerate specimens that contained normal concentrations of calcium. CONCLUSIONS: Although there was a relatively high prevalence of calcium salts in degenerate tendons, which might contribute to the pathological process (such as increased matrix collagen degradation), these data are consistent with the hypothesis that 9dystrophic calcification9 of degenerate tendon matrix is a pathological entity distinct from cell mediated 9calcifying tendinitis9. Calcification is probably one possible outcome (or end point) of chronic tendon injury, although the possibility exists that in many cases, the presence of calcium salts may contribute to the tendon matrix degeneration.
Abstract 4025: SHIP-1 is involved in resistance to alkyl-lysophospholipid induced apoptosis in S49 T-cell lymphoma cells
Authors: Maaike Alderliesten, Jeffrey Klarenbeek, Arnold van der Luit, Menno van Lummel, Wim van Blitterswijk, Marcel Verheij
Journal: Cancer Research (2010)

Abstract Edelfosine (ALP, Et-18-OCH3) is a prototype alkyl-lysophospholipid that has effective antitumoral activity. It inserts in the membrane and accumulates in lipid rafts leading to apoptosis in S49 mouse T cell lymphoma cells. A variant cell line, made resistant to ALP (S49AR) shows in impaired uptake of ALP. S49AR cells are not only resistant to a variety of ALP analogues, but also to DNA damage and Fas/CD95 death receptor induced apoptosis, suggesting another cause for resistance in addition to impaired ALP uptake. Here we studied the ALP resistance of S49AR. We observe an upregulation of phosho-PKB/Akt and phospho-ERK1/2 which are key proteins in the canonical survival signaling pathways. However inhibition of ERK and/or PKB/Akt using pharmacological inhibitors has no effect on the resistance of the S49AR cells to apoptotic stimuli. PKB/Akt and ERK1/2 activation is regulated by PI(3,4,5)P3 formation. The levels of phosphoinositides in the various cell lines were measured with HPLC. The cell lines resistant to apoptotic inducing agents show decreased levels of the diverse phosphopoinositides. SHIP-1 is a SH2 domain containing inositol phosphatase that removes the 5′ phosphate of PI(3,4,5)P3 and is mainly expressed in hemotopoietic cells. It decreases the pool of PI(3,4,5)P3 thereby negatively regulating the activation of PKB/Akt. We see down regulation of SHIP-1 both on gene expression and protein level in the S49AR compared to S49 cells. Other components of the phosphoinositide metabolism, like PI3Kinase and SHIP2, did not show any changes. Resensitization of the S49AR cells to ALP leads to restoration of SHIP-1 expression. Knocking down SHIP-1 using siRNA causes resistance to various ALPs, DNA damage and Fas/CD95 death receptor induced apoptosis. Microarray analysis show that the S49AR and S49siSHIP cells show remarkably similar expression profile which are distinct from the expression profiles shown by S49 and S49mock cells. Concluding, SHIP-1 is downregulated in ALP resistant T cell lymphoma cells concurrent with a general downregulation of phosphoinositide levels in the cells which is associated with the resistance to ALP induced apoptosis. How ALP resistance is caused is yet unknown and is the scope of current research. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4025.
Experiment in Progressive Patient Care
Authors: R. Hartley, W. R. O'Flynn, M. Rake, M. Wooster
Journal: BMJ (1968)

A successful experiment is described in providing total progressive patient care in a small hospital. This was based on dividing ward services into nursing and “hotel” services, the latter being provided by a housekeeping team. Patients were divided into three categories according to the amount of nursing care needed, and two wards were converted, one into an intensive care unit, the other into a homeward bound unit, with high and low nurse/patient ratios respectively.
Episodic Luteinizing Hormone Secretion in Man PULSE ANALYSIS, CLINICAL INTERPRETATION, PHYSIOLOGIC MECHANISMS
Authors: R. J. Santen, C. W. Bardin
Journal: Journal of Clinical Investigation (1973)

The demonstration that luteinizing hormone (LH) release from the pituitary is episodic rather than constant raises fundamental questions regarding the physiologic control of pulsatile LH secretion and its possible alteration in patients with gonadal disorders. To evaluate this mode of LH secretion, quantitative means of analyzing LH pulse amplitude, frequency, shape, and area were established and utilized to study normal subjects and patients with disorders of gonadotropin secretion. Similar patterns of LH secretion were observed in normal men, in women during the follicular phase of the menstrual cycle, and in patients with hyper- and hypogonadotropism, hirsuitism, and amenorrhea (mean pulse amplitude 39-179% from nadir to peak, frequency 2.7-3.9 secretory spikes/6 h). These observations suggested that the pattern of LH secretion is similar in both normal individuals and in those with a variety of pathologic conditions. By contrast, the pattern of pulsatile secretion appeared to differ in the following conditions. LH pulses of higher amplitude (333+/-170%) and lower frequency (1.6+/-0.24 SEM/6 h) characterized the secretory patterns of women during the luteal phase of the menstrual cycle, suggesting that gonadal steroids may modulate LH pulses. LH pulses of low amplitude (26+/-2.1%) and frequency (1.3+/-0.36/6 h) were observed in women with anorexia nervosa. Either integrated LH levels or a mean LH level determined from multiple samples provided a more accurate reflection of gonadotropin secretion than the use of single LH measurements. With multiple sampling over 6 h, it was possible to reduce the 95% confidence limit of LH estimates from +/-50-90 to +/-12%. This allowed normal subjects to be distinguished from patients with low or moderately elevated LH levels in whom gonadotropin levels in single samples were often in the "normal range."Several aspects of the physiologic control of pulsatile LH secretion were studied. The concordance of follicle-stimulating hormone (FSH) with LH pulses progressively increased as LH pulse height increased (P < 0.01) suggesting possible hypothalamic mediation of gonadotropin pulses. Measurement of the "apparent half-life" of LH after secretory spikes revealed half times of 34-233 min. It is likely that this variability was attributable to at least two phenomena: (a) constant low level LH secretion that continued after certain secretory episodes but not others; (b) variable mixing of newly secreted LH into at least two pools. The alpha adrenergic-blocking agents, chlorpromazine and phentolamine, failed to block LH secretory spikes at doses sufficient to result in a 30 mm drop in systolic blood pressure in normal men.
Diagnosis of herpes: comparative virological studies
Authors: P. Laugier, F. Paccaud, M. Orusco, N. Hunziker, M. Monnard
Journal: British Journal of Dermatology (1974)

Journal Article Diagnosis of herpes: comparative virological studies Get access P. Laugier, P. Laugier Search for other works by this author on: Oxford Academic Google Scholar F. Paccaud, F. Paccaud Search for other works by this author on: Oxford Academic Google Scholar M. Orusco, M. Orusco Search for other works by this author on: Oxford Academic Google Scholar N. Hunziker, N. Hunziker Search for other works by this author on: Oxford Academic Google Scholar M. Monnard M. Monnard Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 91, Issue s10, 1 July 1974, Pages 28–29, https://doi.org/10.1111/j.1365-2133.1974.tb12494.x Published: 01 July 1974
The Intensive Care Complex
Authors: Arthur O. Phinney
Journal: JAMA (1969)

<h3>To the Editor:—</h3> The article by Vreeland and Ellis (<b>208</b>:332, 1969), "Stresses on the Nurse in an Intensive Care Unit," emphasizes again the urgent need for recognition by the hospital and nursing administrations of the entirely different tempo, and aggressive type of emergency care required for critically ill patients. Although the article deals with a postsurgical intensive care unit (ICU), the warning applies equally to a cardiology or coronary unit (CICU). The training and orientation of the nurse must be specially adapted to the needs of the short-term, acutely ill, and usually monitored patient. The anxiety resulting from insecurity in her knowledge or inexperience in training should not be allowed to jeopardize either her capabilities or the efficiency of the whole ICU complex. The increased responsibilities expected of nurses in the care of patients likely to suffer cardiopulmonary arrest requires more up-dated, long-range administrative planning and orientation than ordinarily
Abstract 3178: Can DNA from archived formalin-fixed paraffin embedded (FFPE) cancer tissues be used for somatic mutation analysis in next generation sequencing
Authors: Emanuele Palescandolo, Robert Jones, Alina Raza, Ashwini Sunkavalli, Priscilla K. Brastianos, Matthew Ducar, Christina Go, Christine Roden, Charles Hatton, Megan Hanna, Adri Mills, Ravali Adusumilli, Prateek Kumar, Matthew L. Meyerson, Hahn C. William, Laura MacConaill, Paul Van Hummelen
Journal: Cancer Research (2012)

Abstract Formalin-fixed paraffin embedded (FFPE) tissues are far more abundant in most tissue banks and pathology departments than fresh or fresh frozen (FF) samples, but typically yield varying degrees of degraded DNA as a result of the fixation process. The quality of FFPE tissues may vary based on a number of factors such as: age of the block, fixation time, storage and handling conditions. Being able to harness the power of next generation sequencing technologies to genomically characterize these abundant and diverse achieved samples would be tremendously valuable to the cancer research community and would enable the use of this material for clinical purposes. The goal of this study was to assess the performance of FFPE samples in next generation sequencing applications. We monitored close to 100 samples from tumor and normal tissues of FFPE, FF and blood origin. These samples underwent several processes for whole-exome or targeted sequencing, including DNA fragmentation, size selection, library preparation, and hybrid-capture enrichment. We observed variable performance across these samples at several of the above steps, which correlated predominantly with FFPE tissues and the age of block. Other quality metrics that showed relative lower performance of FFPE DNA were the cluster density, duplication rate or library complexity. Most FFPE samples still generated good quality sequence, however, older FFPE blocks, over 10 years, may need more input DNA or higher sequence depth to reach minimum coverage if somatic mutation analysis is the goal. There was no difference in performance between DNA from tumor and normal tissues. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3178. doi:1538-7445.AM2012-3178
Asthma: Attitude and Milieu
Authors: William B. Sherman
Journal: JAMA (1967)

It is refreshing to read a book dedicated to the Hippocratic view that "it is more important to know what kind of a person has a disease than to know what sort of disease a person has." This is a study of the interpersonal relationships and attitudes of 100 patients with asthma, by eight English general practitioners with psychiatric orientation but no special training in the field. The severity of asthma was judged by the number of emergency calls, or the frequency of office visits. Eight of the 100 patients died; information concerning their terminal illnesses is scanty or lacking. Instead of the familiar classification of pollen asthma, infective asthma, and intrinsic asthma, the patients are categorized, largely on the basis of their cooperation, as "demanding babies," "going-his-own-way," "handsoff," etc. The author indicates a considerable incidence of emotional stress and instability in the patients and their families. Conclusions as to
The oestrogen receptor 2 (<i>ESR2</i>) gene in female-pattern hair loss: replication of association with rs10137185 in German patients
Authors: S. Redler, P. Birch, D. Drichel, P. Hofmann, K. Dobson, A.C. Böhmer, J. Becker, K.A. Giehl, R. Tazi-Ahnini, R. Kruse, H. Wolff, A. Miesel, T. Fischer, M. Böhm, R. Nuwayhid, N. Garcia Bartels, G. Lutz, T. Becker, U. Blume-Peytavi, M.M. Nöthen, A.G. Messenger, R.C. Betz
Journal: British Journal of Dermatology (2013)

Funding sources: German Research Foundation DFG, BONFOR programme of the Medical faculty of the University of Bonn. Conflicts of interest: None declared Dear Editor, The aetiopathogenesis of female pattern hair loss (FPHL) is poorly understood. Although research has strongly implicated genetic factors in familial occurrence,1 2 no association finding for FPHL has yet been replicated.3 4 5 Consequently, no causal biological pathways can be suggested on the basis of currently available genetic findings. A recent genome‐wide association study of ESR2 (oestrogen receptor 2) investigated 32 tag single‐nucleotide polymorphisms (SNPs) in an Australian FPHL sample and found nominal significance for three variants (rs10137185, rs17101774, rs2022748). The most significant SNP was rs10137185 (P = 0·003 for genotype CC versus genotypes CT + TT).6 This effect was consistent across subgroups stratified for disease severity and age‐at‐onset. Although no finding withstood experiment‐wide correction for multiple testing, the validity of the association with rs10137185 was supported by functional evidence from a public eQTL database, i.e. an association between the risk genotype CC and higher ESR2 expression levels in fibroblasts. This latter finding is consistent with reports that oestrogen has inhibitory effects on hair growth.7 In a previous study, we investigated four variants in the ESR2 gene in a U.K./German FPHL sample and found no association.5 However, this may have been attributable to the fact that none of these four variants were in strong linkage disequilibrium with variants showing association in the Australian sample (max. r2 = 0·149).
MUMPS OF THE TESTES WITHOUT PAROTITIS
Authors: Ralph W. Danielson
Journal: JAMA (1927)

Textbooks mention that mumps of the testes without parotitis can occur, yet one finds very few case reports in the literature. Torpey<sup>1</sup>reported a somewhat similar case in 1911, in which primary orchitis was followed by parotitis. The most complete recent paper on cases of orchitis without parotitis is that of Bathait.<sup>2</sup>This dearth of reports cannot be due to commonplaceness and frequency. I have inquired of many physicians, but found only one who had seen a parallel case. <h3>REPORT OF CASE</h3> July 2, 1927, I was called to see a medium-sized, muscular, but spare man, aged 44, complaining of chills, fever, painful and swollen testes, and general aching especially in the lumbar region. He had been sick three days with the same complaints, except that there had been transitory cramping in the abdomen at the onset, and the testicular swelling was becoming progressively worse. The patient looked sick.
Recurrent Pulmonary Embolism and Chronic Multivessel Thrombophlebitis Associated With a Right-to-Left Shunt in the Antiphospholipid Syndrome
Authors: JENS BREMERICH, JAN M??LLER-BRAND
Journal: Clinical Nuclear Medicine (1995)

A 51-year-old woman had chronic thrombophlebitis of the right axillary, right subclavian, upper mesenteric, and caval veins associated with recurrent pulmonary embolism. Permanent antlcoagulatlon had been instituted. She manifested characteristics of the Antiphospholipid syndrome, including elevated IgG-cardiollpin antibody titers, habitual abortions, livedo reticularis, and skin ulcers.
A mutation in the lipoprotein lipase gene is the molecular basis of chylomicronemia in a colony of domestic cats.
Authors: D G Ginzinger, M E Lewis, Y Ma, B R Jones, G Liu, S D Jones
Journal: Journal of Clinical Investigation (1996)

Members of a domestic cat colony with chylomicronemia share many phenotypic features with human lipoprotein lipase (LPL) deficiency. Biochemical analysis reveals that these cats do have defective LPL catalytic activity and have a clinical phenotype very similar to human LPL deficiency. To determine the molecular basis underlying this biochemical phenotype, we have cloned the normal and affected cat LPL cDNAs and shown that the affected cat has a nucleotide change resulting in a substitution of arginine for glycine at residue 412 in exon 8. In vitro mutagenesis and expression studies, in addition to segregation analysis, have shown that this DNA change is the cause of LPL deficiency in this cat colony. Reduced body mass, growth rates, and increased stillbirth rates are observed in cats homozygous for this mutation. These findings show that this LPL deficient cat can serve as an animal model of human LPL deficiency and will be useful for in vivo investigation of the relationship between triglyceride rich lipoproteins and atherogenic risk and for the assessment of new approaches for treatment of LPL deficiency, including gene therapy.
Shall The Journal be Removed to Washington?
Authors: Henry O. Marcy
Journal: JAMA (1891)

<h3>To the Editor:</h3> —I have waited until the present before expressing my opinion upon the action of the Trustees ofThe Journal, at their late meeting, advising that at the end of the present year,The Journalshould be permanently established in a central office at Washington. The only argument offered in favor of the change was by one of the new Trustees who stated that<i>he voted for it because he was pledged to that course of action before his appointment</i>. Few know better than myself the events which led to the establishment ofThe Journaland its location in Chicago. It was but natural to expect that there would exist a rivalry between the leading centres of our great country for its possession, since it is easy to understand the power and influence which such a journal might exert if made the exponent of local interests. Fortunately for