tbuckley/cabot-search huggingface dataset:
Gynaecological consultation in patients with the irritable bowel syndrome.
Authors: A Prior, P J Whorwell
Journal: Gut (1989)

A 12 month follow up study to assess the impact of symptoms suggestive of irritable bowel syndrome in women presenting to gynaecology clinics with pelvic pain is reported. Of 71 women 37 (52%) had symptoms suggestive of irritable bowel syndrome at presentation. A firm gynaecological diagnosis was reached in only three (8%) women positive for irritable bowel syndrome compared with 15 (44%) without (p = 0.002). After 12 months 24 (65%) women with irritable bowel syndrome were still symptomatic compared with 11 (32%) without (p = 0.01). This study shows that women with irritable bowel syndrome frequently attend gynaecological clinics but rarely have gynaecological pathology and the prognosis is poor in terms of resolution of their pain.
Genomic aberrations in pediatric diffuse intrinsic pontine gliomas
Authors: K. E. Warren, K. Killian, M. Suuriniemi, Y. Wang, M. Quezado, P. S. Meltzer
Journal: Neuro-Oncology (2011)

Diagnostic biopsy is not routinely performed for children with diffuse intrinsic pontine glioma (DIPG). Consequently, our understanding of DIPG biology is hindered by limited tissue availability. We performed comparative genomic hybridization (CGH) on autopsy specimens to examine the feasibility of determining DNA genomic copy number aberrations on formalin-fixed, paraffin-embedded (FFPE) blocks. Histology on FFPE blocks obtained from autopsy of pediatric patients with DIPG was reviewed. Regions were marked for processing, and DNA was extracted from the tissue core, labeled by chemical coupling with Cy5, and hybridized to 105K oligonucleotide CGH arrays. After hybridization and washing, arrays were scanned, and data segmented and processed with Nexus software. Twenty-two samples from 13 subjects were obtained. Histologic variability was noted. CGH was successfully performed on 18 of 22 samples, representing 11 of 13 subjects. All demonstrated DNA copy number abnormalities. High copy number amplification of known oncogenes and homozygous deletions of known tumor suppressor genes were observed. Additional regions of high copy number amplification and homozygous deletion and geographical variations in the CGH patterns were found. CGH performed on FFPE tissue obtained from autopsy yields satisfactory results. This sample set from patients with DIPG was highly informative, with the majority of specimens showing ≥1 abnormality related to a known cancer gene. Aberrations in candidate drug targets were observed. This study establishes the feasibility of genomic DNA analysis from DIPG autopsy material, identifies several targets for which molecular targeted therapy exists, and suggests significant heterogeneity among patients with DIPG.
Cross-talk between G Protein–Coupled Receptor and Epidermal Growth Factor Receptor Signaling Pathways Contributes to Growth and Invasion of Head and Neck Squamous Cell Carcinoma
Authors: Sufi Mary Thomas, Neil E. Bhola, Qing Zhang, Sarah C. Contrucci, Abbey L. Wentzel, Maria L. Freilino, William E. Gooding, Jill M. Siegfried, Daniel C. Chan, Jennifer Rubin Grandis
Journal: Cancer Research (2006)

Abstract G protein–coupled receptors (GPCR) and the epidermal growth factor receptor (EGFR) are often both overexpressed and contribute to the growth of cancers by activating autocrine pathways. GPCR ligands have been reported to trigger EGFR signaling via receptor cross-talk in cancer cells. Here, we show that GPCR ligands prostaglandin E2 (PGE2) and bradykinin (BK) activate EGFR signaling. Inhibition of EGFR using several strategies, including small-molecule inhibitors and an EGFR-specific antibody, resulted in partial attenuation of signaling downstream of EGFR. PGE2 and BK triggered EGFR signaling by increasing selective autocrine release of transforming growth factor-α (TGF-α). Inhibition of tumor necrosis factor-α–converting enzyme abrogated BK- or PGE2-mediated activation of EGFR signaling. Both PGE2 and BK stimulated head and neck squamous cell carcinoma (HNSCC) invasion via EGFR. Treatment of HNSCC cells with the BK antagonist CU201 resulted in growth inhibition. The combination of CU201 with the EGFR small-molecule inhibitor erlotinib resulted in additive inhibitory effects on HNSCC cell growth in vitro. Inhibition of the PGE2 synthesis pathway with sulindac induced HNSCC cytotoxicity at high doses (EC50, 620 μmol/L). However, combined inhibition of both EGFR with the tyrosine kinase inhibitor erlotinib and GPCR with sulindac at low doses of 6 and 310 μmol/L, respectively, resulted in synergistic killing of HNSCC tumor cells. Combined blockade of both EGFR and GPCRs may be a rational strategy to treat cancers, including HNSCC that shows cross-talk between GPCR and EGFR signaling pathways. (Cancer Res 2006; 66(24): 11831-9)
Plasma protein turnover (albumin, transferrin, IgG, IgM) in Menetrier's disease (giant hypertrophic gastritis): Evidence of non-selective protein loss
Authors: S. Jarnum, K. B. Jensen
Journal: Gut (1972)

Ten cases of Ménétrier's disease (;giant hypertrophic gastritis') have been studied with radioiodine-labelled albumin (all 10 cases), IgG (eight cases), transferrin (two cases), and IgM (six cases). Abnormal gastric loss of plasma protein was present in all cases as demonstrated by (59)Fe-iron dextran (eight cases), (51)Cr-albumin (one case), and (131)I-polyvinylpyrrolidone (one case). None of the patients had more distal gastrointestinal lesions. The synthetic rate of the proteins studied was normal or slightly elevated. The fractional catabolic rate of the proteins was increased. The increase above the normal mean was similar for albumin, transferrin, and IgG. Since the molecular weight of IgG is more than twice that of albumin and transferrin, it is concluded that the protein loss in Ménétrier's disease is nonselective in the sense that it affects a similar fraction of the intravascular masses of all plasma proteins. IgM catabolism was strongly accelerated. Simultaneous studies with (50)Fe-iron dextran, radioiodine-labelled albumin or IgG showed that IgM hypercatabolism could only partly be due to abnormal gastric protein loss, since IgM catabolism was significantly more raised than that of albumin and IgG. Faecal radioiodine excretion was normal in most patients after the injection of radioiodine-labelled proteins. It confirms a previous observation that increased gastrointestinal (59)Fe clearance after injection of (59)Fe-iron dextran associated with normal faecal radioiodine excretion after the injection of radioiodine-labelled proteins permits of a diagnosis of protein loss in the stomach.
Regulation of Prostaglandin Metabolism by Calcitriol Attenuates Growth Stimulation in Prostate Cancer Cells
Authors: Jacqueline Moreno, Aruna V. Krishnan, Srilatha Swami, Larisa Nonn, Donna M. Peehl, David Feldman
Journal: Cancer Research (2005)

Abstract Calcitriol exhibits antiproliferative and prodifferentiation effects in prostate cancer. Our goal is to further define the mechanisms underlying these actions. We studied established human prostate cancer cell lines and primary prostatic epithelial cells and showed that calcitriol regulated the expression of genes involved in the metabolism of prostaglandins (PGs), known stimulators of prostate cell growth. Calcitriol significantly repressed the mRNA and protein expression of prostaglandin endoperoxide synthase/cyclooxygenase-2 (COX-2), the key PG synthesis enzyme. Calcitriol also up-regulated the expression of 15-hydroxyprostaglandin dehydrogenase, the enzyme initiating PG catabolism. This dual action was associated with decreased prostaglandin E2 secretion into the conditioned media of prostate cancer cells exposed to calcitriol. Calcitriol also repressed the mRNA expression of the PG receptors EP2 and FP, providing a potential additional mechanism of suppression of the biological activity of PGs. Calcitriol treatment attenuated PG-mediated functional responses, including the stimulation of prostate cancer cell growth. The combination of calcitriol with nonsteroidal anti-inflammatory drugs (NSAIDs) synergistically acted to achieve significant prostate cancer cell growth inhibition at ∼2 to 10 times lower concentrations of the drugs than when used alone. In conclusion, the regulation of PG metabolism and biological actions constitutes a novel pathway of calcitriol action that may contribute to its antiproliferative effects in prostate cells. We propose that a combination of calcitriol and nonselective NSAIDs might be a useful chemopreventive and/or therapeutic strategy in men with prostate cancer, as it would allow the use of lower concentrations of both drugs, thereby reducing their toxic side effects.
Plasma vitamin D concentration and clinical characteristics in clinically stable patients with moderate COPD
Authors: Elisabeth Romme, Lidwien Graat-Verboom, Erica Rutten, Frank Smeenk, Martijn Spruit, Emiel Wouters
Journal: European Respiratory Journal (2011)

Introduction:  Vitamin D deficiency is associated with poor functional performance in patients with COPD. However, most research is limited to patients with severe COPD, whilst vitamin D deficiency also occurs in GOLD stage II patients (Janssens et al. Thorax 2010). Therefore, we aimed to investigate differences in clinical characteristics in clinically stable GOLD stage II patients with and without vitamin D deficiency.   Methods:  159 patients with COPD GOLD stage II (age 69±9 yrs; FEV 1  65±9% pred; 58% men) recruited at the outpatient consultation office of the Catharina Hospital were included. Vitamin D deficiency was defined as plasma 25(OH)D concentration  1 , RV/TLC, arterial pO 2 , MRC dyspnea, six-minute walk distance (6MWD) and score on the BODE index were assessed. The number of sunshine hours 2 months before blood sampling was determined using data from the Royal Netherlands Meteorological Institute.   Results:  Vitamin D deficient patients had higher RV/TLC, lower pO 2 , worse 6MWD, higher BODE score and less sunshine hours.  After correction for confounders, vitamin D deficiency was associated with lower pO 2 , higher BODE score and less sunshine hours (all p≤0.03).   Conclusions:  Vitamin D deficiency is common in COPD GOLD stage II patients. Moreover, patients with vitamin D deficiency were characterized by lower arterial pO 2 , worse exercise performance and higher BODE score.
Infectious complications in 127 patients with hairy cell leukemia
Authors: Harvey M. Golomb, Laura J. Hadad
Journal: American Journal of Hematology (1984)

Abstract Information regarding infectious complications was obtained on 127 patients with hairy cell leukemia who were diagnosed between March 1974 and April 1982. Forty‐seven patients (37%) had 111 documented infections (cultures positive), and 40 patients (31.5%) had 113 nondocumented infections (no culture results available, or cultures negative). The remaining 40 patients (31.5%) had no significant infections during the course of their disease. Patients without infection lived significantly longer than did patients who developed an infection (92% v 49% were alive at 4 years; P = .0012). Thirty‐three of the 47 patients with documented infection have died; 29 of an infectious problem and four of a noninfectious problem. There was also a statistically significant difference in actuarial survivals between the documented‐infection and nondocumented infection groups ( P = .007). The two most common types of infection were bacteremia (30 episodes) and pneumonia (27 episodes). In the culture‐documented group with bacteremia, E coli and P aeruginosa caused ten and eight infections, respectively, and three infections were due to S aureus. There were eight systemic infections of nonbacterial origin; in five, the organism cultured was M kansasii, and three were fungal infections. Blood counts at the time of diagnosis were not correlated with subsequent development of infection. Patients with hairy cell leukemia have a significant susceptibility to infections that can affect morbidity and mortality. Many of the infectious complications encountered are those common in patients whose immune system is compromised; however, the occurrence of disseminated atypical mycobacterial disease requires a heightened awareness.
Jaundice in Older Children and Adults
Authors: J. Donald Ostrow
Journal: JAMA (1975)

JAUNDICE is the yellow discoloration of the skin and eyes that is caused by retention of bilirubin, the major catabolic product of heme. A few other pigments, such as carotene and lycopene, may also cause yellowing of the skin, but characteristically do not cause discoloration of the sclerae. The algorithm (Fig 1) is intended to apply only to older children and adults; it is not applicable to the differential diagnosis of jaundice in the neonate or very young child. A brief overview of the approach to the differential diagnosis of jaundice is given in an earlier communication,<sup>1</sup>and an audiovisual program that summarizes much of the information to follow is available from the American Gastroenterological Association and the General Services Administration of the US government.<sup>2-4</sup>More detailed overviews of bilirubin metabolism have been given by Schmid<sup>5</sup>and Fleischner and Arias.<sup>6</sup> The initial step in the
Expression of interferon in synovial tissue from patients with rheumatoid arthritis: comparison with patients with osteoarthritis and reactive arthritis
Authors: J van Holten
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> IFNβ may have immunomodulatory effects in rheumatoid arthritis (RA) and its increased production in RA synovium may be a reactive attempt to inhibit inflammation. <b>Objective:</b> To determine the expression of IFNβ in the synovial tissue of patients with RA, osteoarthritis, and reactive arthritis. <b>Methods:</b> Synovial biopsy specimens were obtained by arthroscopy from patients with RA and disease controls for immunohistological analysis using a monoclonal antibody specific for IFNβ. Bound antibody was detected by an immunoperoxidase method. Stained sections were evaluated by computer assisted image analysis. Double stainings were performed with antibodies to detect CD55 positive fibroblast-like synoviocytes (FLS), CD68 positive macrophages, and CD83 positive dendritic cells (DCs) coexpressing IFNβ. <b>Results:</b> IFNβ protein was abundantly expressed in the synovium of patients with RA. Digital image analysis showed a significant increase in the mean integrated optical density for IFNβ expression in RA synovial tissue compared with disease controls. Specific up regulation of IFNβ expression was also seen when the results were controlled for cell numbers. Phenotypic analysis showed that FLS, especially, but also macrophages and DCs may express IFNβ in RA synovial tissue. <b>Conclusions:</b> The increased expression of IFNβ in RA synovium suggests activation of an immunomodulatory mechanism that could inhibit synovial inflammation.
IGFBP Ratio Confers Resistance to IGF Targeting and Correlates with Increased Invasion and Poor Outcome in Breast Tumors
Authors: Marc A. Becker, Xiaonan Hou, Sean C. Harrington, S. John Weroha, Sergio E. Gonzalez, Kristina A. Jacob, Joan M. Carboni, Marco M. Gottardis, Paul Haluska
Journal: Clinical Cancer Research (2012)

Abstract Purpose: To improve the significance of insulin-like growth factor–binding protein 5 (IGFBP-5) as a prognostic and potentially predictive marker in patients with breast cancer. Experimental Design: Increased IGFBP-5 expression was identified in MCF-7 cells resistant (MCF-7R4) to the IGF-1R/insulin receptor (InsR) inhibitor BMS-536924 and its role examined by targeted knockdown and overexpression in multiple experimental models. Protein expression of IGFBP-5 was measured by immunohistochemistry in a cohort of 76 patients with breast cancer to examine correlative associations with invasive tumor fraction and outcome. The use of a combined IGFBP-5/IGFBP-4 (BPR) expression ratio was applied to predict anti-IGF-1R/InsR response in a panel of breast cancer lines and outcome in multiple breast tumor cohorts. Results: IGFBP-5 knockdown decreased BMS-536924 resistance in MCF-7R4 cells, whereas IGFBP-5 overexpression in MCF-7 cells conferred resistance. When compared with pathologically normal reduction mammoplasty tissue, IGFBP-5 expression levels were upregulated in both invasive and histologically normal adjacent breast cancer tissue. In both univariate and multivariate modeling, metastasis-free survival, recurrence free survival (RFS), and overall survival (OS) were significantly associated with high IGFBP-5 expression. Prognostic power of IGFBP-5 was further increased with the addition of IGFBP-4 where tumors were ranked based upon IGFBP-5/IGFBP-4 expression ratio (BPR). Multiple breast cancer cohorts confirm that BPR (high vs. low) was a strong predictor of RFS and OS. Conclusion: IGFBP-5 expression is a marker of poor outcome in patients with breast cancer. An IGFBP-5/IGFBP-4 expression ratio may serve as a surrogate biomarker of IGF pathway activation and predict sensitivity to anti-IGF-1R targeting. Clin Cancer Res; 18(6); 1808–17. ©2012 AACR.
New rheumatoid arthritis genetic factor and C5 serum level
Authors: H Mbarek, M Kallel-Sellami, Y Zerzri, K Dawidowicz, K Mejri, T Bardin, B Prum, P Dieudé, E Petit-Teixeira, F Cornélis, S Makni
Journal: Annals of the Rheumatic Diseases (2009)

There is a significant body of evidence suggesting that complement activation plays an important role in the maintenance of the polyarticular chronic synovitis characteristic of rheumatoid arthritis (RA).1 Recently, a novel RA genetic risk factor was described, involving allelic polymorphisms on the chromosome 9, in the intergenic region between complement factor 5 ( C5 ) and tumour necrosis factor receptor-associated factor 1 ( TRAF1 ) genes.2,3,4 The new genetic factor, detected in RA case-control studies for anti-cyclic citrullinated peptide antibodies and/or rheumatoid factor positive (RF+) RA in North American, Swedish and Dutch populations,2,3 was confirmed by linkage in a …
Cyclooxygenase-2 Expression in Postmastectomy Chest Wall Relapse
Authors: Janet H. Kim, Veerle Bossuyt, Teresa Ponn, Donald Lannin, Bruce G. Haffty
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Cyclooxygenase-2 (COX-2) expression has been shown to be associated with radiation resistance, which theoretically could be overcome with the use of COX-2 inhibitors. The purpose of this study was to assess the prognostic significance and clinical correlations of COX-2 expression (COX) in a cohort of patients treated with radiation for postmastectomy chest wall relapse. Experimental Design: Between 1975 and 1999, 113 patients were treated for isolated postmastectomy chest wall relapse. All patients were treated with biopsy and/or excision of the chest wall recurrence followed by radiation therapy. Median follow-up was 10 years. All clinical data, including demographics, pathology, staging, receptor status, HER-2/neu status, and adjuvant therapy, were entered into a computerized database. Paraffin-embedded chest wall recurrence specimens were retrieved from 42 patients, of which 38 were evaluated, created into a tissue microarray, stained by immunohistochemical methods for COX, and graded 0 to 3+. A score of 2 to 3+ was considered positive. Results: Overall survival from original diagnosis for entire cohort was 44% at 10 years. Survival rate after chest wall recurrence was 28% at 10 years. The distant metastasis-free survival rate after chest wall recurrence was 40% at 10 years. Local-regional control of disease was achieved in 79% at 10 years after chest wall recurrence. COX was considered positive in 13 of 38 cases. COX was inversely correlated with estrogen receptor (P = 0.045) and progesterone receptor (P = 0.028), and positively correlated with HER-2/neu (P = 0.003). COX was also associated with a shorter time to postmastectomy chest wall relapse. The distant metastasis-free rate for COX-negative patients was 70% at 10 years, compared with 31% at 10 years for COX-2–positive patients (P = 0.029). COX positive had a poorer local-regional progression-free rate of 19% at 10 years, compared with 81% at 10 years for COX negative. This was of high statistical significance with a P value of 0.003. Conclusions: Outcome following radiation therapy for postmastectomy chest wall relapse is relatively poor. Positive COX correlated with other markers of poor outcome, including a shorter time to local relapse, negative estrogen receptor/progesterone receptor, and positive Her-2/neu status. Positive COX correlated with higher distant metastasis and lower local-regional control of disease. If confirmed with larger studies, these data have implications with respect to the concurrent use of COX-2 inhibitors and radiation for postmastectomy chest wall relapse.
Conventional and Complementary Therapies: A Tale of Two Research Standards?
Authors: Mark N. Levine
Journal: Journal of Clinical Oncology (2010)

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THE ROLE CONCEPT, A BRIDGE BETWEEN PSYCHIATRY AND SOCIOLOGY
Authors: J. L MORENO
Journal: American Journal of Psychiatry (1961)

The concept underlying this approach is the recognition that man is a role player, that every individual is characterized by a certain range of roles which dominate his behavior, and that every culture is characterized by a certain set of roles which it imposes with a varying degree of success upon its membership(21). In contrast to the theories presented by psychologists and sociologists "psychiatric role theory" developed largely out of clinical contexts, methods of prevention, treatment of psychoses and neuroses, of marriage and family groups, of interpersonal relations, of problems of industrial adjustment, of the fields of mental hygiene and education. Role research and role therapy are still in their infancy. Psychodrama presents a valuable vehicle for experimental and control studies of roles. It permits the observation of individuals in live situations in which they are concretely involved.
Electrophysiological study of the action of angiotensin II on the rat myometrium.
Authors: G Hamon, M Worcel
Journal: Circulation Research (1979)

Angiotensin II (A II) produces a contraction of visceral and vascular smooth muscles of different species. The accompanying electrophysiological changes were measured on strips of rat myometrium at 35 degrees C using the double sucrose-gap technique. A II at concentrations from 5 x 10(-10) to 10(-6)M produces a depolarization and an increase in membrane conductance. This increase in membrane conductance is not membrane potential dependent since it is observed even when the membrane potential is maintained at the resting level. When all Na + in the test solution is replaced by either Li + or Mg (2+), the depolarizing effect of 10(-6)M A II is either markedly reduced or abolished. Under these conditions, A II produces a small initial hyperpolarization, which is modified by external potassium concentration changes and abolished by tetraethylammonium chloride. When all Cl- is replaced by either NO (-3) or cyclohexanesulfamate, A II (10(-6) M) still produces a 20-m V depolarization. The removal of extracellular Ca (2+) or K+ does not have any effect on the depolarizing action of A II, which also is not changed by 10(-3) M ouabain. In conclusion, A II produces a depolarization of the uterine smooth muscle membrane through an increase in the membrane conductance to Na+. The membrane conductance to potassium is increased simultaneously. The contraction induced by A II shows two components: a phasic component triggered by the Ca (2+) entry associated with spike production and a tonic component due to the release of Ca(2+) from intracellular stores.