tbuckley/cabot-search huggingface dataset:
Identification of interleukin-13 receptor α2 chain overexpression in situ in high-grade diffusely infiltrative pediatric brainstem glioma
Authors: Bharat H. Joshi, Rada A. Puri, Pamela Leland, Frederick Varricchio, Ghanshyam Gupta, Mehmet Kocak, Richard J. Gilbertson, Raj K. Puri
Journal: Neuro-Oncology (2008)

Neuro-oNcologyHuman malignant glioma cell lines and adult brain tumors overexpress high levels of interleukin-13 receptor a2 chain (IL-13Ra2).Because the IL-13Ra2 chain is an important target for cancer therapy and prognosis for patients with brainstem glioma (BSG) remains dismal, we investigated the expression of this receptor in specimens of diffusely infiltrative pediatric BSG relative to normal brain tissue.Twenty-eight BSG specimens and 15 normal brain specimens were investigated for IL-13Ra2 protein expression by immunohistochemical analysis (IHC) using two different antibodies in two different laboratories.Highly sensitive Q-dot-based IHC and in situ hybridization (ISH) assays were also developed to identify IL-13Ra2 protein and RNA in these specimens.The results were evaluated independently in two laboratories in a blinded fashion.By Q-dot IHC or a standard IHC assay, 17 of 28 (61%) tumor specimens Identification of interleukin-13 receptor a2 chain overexpression in situ in high-grade diffusely infiltrative pediatric brainstem glioma
Role of intracellular calcium in superoxide-induced hepatocyte injury
Authors: Masaru Murata, Morito Monden, Koji Umeshita, Hiroshi Nakano, Toshio Kanai, Mitsukazu Gotoh, Takesada Mori
Journal: Hepatology (1994)

The mechanisms of hepatocyte injury caused by exogenous superoxide were investigated with the use of cultured rat hepatocytes. Cell viability, cytosolic free calcium concentration and cell surface structure were observed. Superoxide was produced by adding hypoxanthine and xanthine oxidase to the buffer. Cytosolic free calcium concentration was calculated by means of ratio imaging of fura 2 fluorescence with multiparameter digitized microscopy. In the buffer containing 1.27 mmol/L of calcium, lactate dehydrogenase release into the buffer began to increase at 1 hr and reached a plateau in 5 hr. Eighteen minutes after the addition of hypoxanthine and xanthine oxidase, small blebs were recognized on the cell surface with a scanning electron microscope; then a gradual rise in cytosolic free calcium concentration was observed. Thirty minutes after exposure to superoxide, large blebs were recognized with a phase-contrast microscope, when cytosolic free calcium concentration had risen to about 700 nmol/L. Depriving the buffer of calcium (< 10 mumol/L) significantly suppressed bleb formation and cell death, and cytosolic free calcium concentration was found to remain around the basal level (200 nmol/L). When ethylene glycol-bis (beta-amino-ethyl ether)-N,N,N',N'-tetraacetic acid was added to the buffer, bleb formation and cell death were suppressed more completely, and cytosolic free calcium concentration decreased. Superoxide dismutase combined with catalase or nifedipine allowed the hepatocytes to maintain their viability and suppressed cytosolic free calcium concentration elevation. Calpeptin, a Ca(2+)-dependent neutral protease inhibitor, did not affect the rise in cytosolic free calcium concentration but prevented cell injury.(ABSTRACT TRUNCATED AT 250 WORDS)
Impaired meal stimulated glucagon-like peptide 2 response in ileal resected short bowel patients with intestinal failure
Authors: P B Jeppesen, B Hartmann, B S Hansen, J Thulesen, J J Holst, P B Mortensen
Journal: Gut (1999)

Glucagon-like peptide 2 (GLP-2) is a growth factor for the intestinal epithelium in rodents and may affect intestinal transit.To study the GLP-2 response to nutrient ingestion in seven short bowel patients with intestinal failure and seven controls.The patients and controls were admitted twice for two test meals after a night of fasting. Meal A was liquid (300 ml, 1.88 MJ); meal B was a regular breakfast (755 g, 3.92 MJ). Plasma samples were collected for 180 minutes; GLP-2 immunoreactivity was measured with an NH(2) terminal specific radioimmunoassay.Both meals elicited significant increases in plasma GLP-2 in controls. The magnitude and duration of the responses were dependent on the meal size: the maximum median (25-75%) increases after meal A and B were 24 (3-28) and 48 (33-56) pmol/l. Plasma GLP-2 returned to basal concentrations 180 minutes after meal A, but remained at 50% of peak values after meal B. In the patients neither meal significantly changed the GLP-2 concentration; the maximum median elevation after meal B was 5 (2-8) pmol/l. There were significant differences between patients and controls with respect to the GLP-2 responses to meals A and B.Identification of GLP-2 as a tissue specific intestinal growth factor and demonstration of an impaired meal stimulated GLP-2 response in short bowel patients raises the possibility that GLP-2 administration may constitute a new therapeutic strategy, enhancing jejunal adaptation in ileum resected short bowel patients with intestinal failure.
Quality-of-life impairment in patients with livedoid vasculopathy
Authors: Maria Rita Polo Gascón, Jozélio Freire de Carvalho, Danielle Priscila de Souza Espinel, Alessandra Moraes Barros, Afsaneh Alavi, Paulo Ricardo Criado
Journal: Journal of the American Academy of Dermatology (2014)
Personal Care Product Use Predicts Urinary Concentrations of Some Phthalate Monoesters
Authors: Susan M. Duty, Robin M. Ackerman, Antonia M. Calafat, Russ Hauser
Journal: Environmental Health Perspectives (2005)

Phthalates are multifunctional chemicals used in a variety of applications, including personal care products. The present study explored the relationship between patterns of personal care product use and urinary levels of several phthalate metabolites. Subjects include 406 men who participated in an ongoing semen quality study at the Massachusetts General Hospital Andrology Laboratory between January 2000 and February 2003. A nurse-administered questionnaire was used to determine use of personal care products, including cologne, aftershave, lotions, hair products, and deodorants. Phthalate monoester concentrations were measured in a single spot urine sample by isotope dilution–high-performance liquid chromatography coupled to tandem mass spectrometry. Men who used cologne or aftershave within 48 hr before urine collection had higher median levels of monoethyl phthalate (MEP) (265 and 266 ng/mL, respectively) than those who did not use cologne or aftershave (108 and 133 ng/mL, respectively). For each additional type of product used, MEP increased 33% (95% confidence interval, 14–53%). The use of lotion was associated with lower urinary levels of monobutyl phthalate (MBP) (14.9 ng/mL), monobenzyl phthalate (MBzP) (6.1 ng/mL), and mono(2-ethylhexyl) phthalate (MEHP) (4.4 ng/mL) compared with men who did not use lotion (MBP, 16.8 ng/mL; MBzP, 8.6 ng/mL; MEHP, 7.2 ng/mL). The identification of personal care products as contributors to phthalate body burden is an important step in exposure characterization. Further work in this area is needed to identify other predictors of phthalate exposure.
ANEMIA IN HYPOTHYROIDISM
Authors: GEORGE M. MACKENZIE
Journal: JAMA (1926)

By means of extirpation experiments and from observations on the effects of administering thyroid gland preparations, it has been shown by Esser,<sup>1</sup>Mansfield,<sup>2</sup>Kishi<sup>3</sup>and others, that: (<i>a</i>) after thyroidectomy, dogs and rabbits show a decrease in red cells and hemoglobin amounting usually to about 30 per cent; (<i>b</i>) in animals with an experimentally produced anemia, regeneration is retarded by thyroidectomy; (<i>c</i>) administration of thyroid gland to normal animals may cause an increase of red blood cells up to 15 per cent. For the purpose of this paper it is not necessary to review these experiments in detail. They indicate that under controlled conditions it can be shown that the thyroid hormone exerts a certain influence on hematopoiesis. <h3>THE THYROID AND HEMATOPOIESIS</h3> Numerous clinical observations (Kocher,<sup>4</sup>Falta,<sup>5</sup>Bence and Engel,<sup>6</sup>Janney and Engel,<sup>7</sup>Hutton<sup>8</sup>) also provide unmistakable evidence that disturbances of the
Studies on <i>Fusarium solani</i>
Authors: J. Verma, S. V Gangal
Journal: Allergy (1994)

Allergenic cross‐reactivity among three Fusarium species (F. solani, F. equiseti, and F. moniliforme) was determined by crossed immunoelectrophoresis (CIE), ELISA inhibition, and immunoprint‐inhibition analysis. Inhibiting immunoprint was used to assess the cross‐reactivity of individual allergenic proteins in culture filtrate (CF), separated on SDS‐PAGE. Dose‐response inhibition of band 14 kDa in immunoprints of F. solani CF by antigens of F. solani CF, F. equiseti CF, and F. moniliforme CF demonstrated significant cross‐reactivity of allergenic proteins on analysis of densitometric scans. CIE and ELISA inhibition using hyperimmune sera raised in rabbits against F. solani CF antigen also demonstrated shared antigenicity among Fusarium species. Collectively, this study revealed the presence of shared as well as unique antigenic and allergenic determinants in F. solani CF, F. equiseti CF, and F. moniliforme CF antigens.
Splicing Mutations in <i>KCNQ1</i>
Authors: A. Murray, C. Donger, C. Fenske, I. Spillman, P. Richard, Y. B. Dong, N. Neyroud, P. Chevalier, I. Denjoy, N. Carter, P. Syrris, A. R. Afzal, M. A. Patton, P. Guicheney, S. Jeffery
Journal: Circulation (1999)

Long-QT syndrome is a monogenic disorder that produces cardiac arrhythmias and can lead to sudden death. At least 5 loci and 4 known genes exist in which mutations have been shown to be responsible for the disease. The potassium channel gene KCNQ1, previously named KVLQT1, on chromosome 11p15.5 is one of these.We initially analyzed one family using microsatellite markers and found linkage to KCNQ1. Mutation detection showed a G to C change in the last base of exon 6 (1032 G-->C) that does not alter the coded alanine. Restriction digest analysis in the family showed that only affected individuals carried the mutation. A previous report suggested that a G to A substitution at the same position may act as a splice mutation in KCNQ1, but no data was given to support this hypothesis nor was the transcription product identified. We have shown by reverse-transcription polymerase chain reaction that 2 smaller bands were produced for the KCNQ1 gene transcripts in addition to the normal-sized transcripts when lymphocytes of affected individuals were analyzed. Sequencing these transcripts showed a loss of exon 7 in one and exons 6 and 7 in the other, but an in-frame transcript was left in each instance. We examined other families in whom long-QT syndrome was diagnosed and found another unreported splice-site mutation, 922-1 G-->C, in the acceptor site of intron 5, and 2 of the previously reported 1032 G-->A mutations. All these showed a loss of exons 6 and 7 in the mutant transcripts, validating the proposal that a consensus sequence is affected in the exonic mutations and that the integrity of the base at position 1032 is essential for correct processing of the transcript.The 6 cases already reported in the literature with the 1032 G-->A transition, the novel 1032 G-->C transversion, and a recent G-->T transversion at the same base show that codon 344 is the second most frequently mutated after codon 341, suggesting at least two hotspots for mutations in KCNQ1.
First report of a <i>FXII</i> gene mutation in a Brazilian family with hereditary angio-oedema with normal C1 inhibitor
Authors: C. Stieber, A.S. Grumach, E. Cordeiro, R.N. Constantino-Silva, S. Barth, P. Hoffmann, J.B. Pesquero, T. Renné, M.M. Nöthen, S. Cichon
Journal: British Journal of Dermatology (2015)
Changes of Biochemical Markers of Bone Turnover and YKL-40 Following Hormonal Treatment for Metastatic Prostate Cancer Are Related to Survival
Authors: Julia S. Johansen, Klaus Brasso, Peter Iversen, Børge Teisner, Patrick Garnero, Paul A. Price, Ib Jarle Christensen
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Elevated serum levels of biochemical markers of bone turnover and YKL-40 in patients with metastatic prostate cancer (PC) at the time of diagnosis are associated to poor prognosis. In this study, we evaluated the value of these biomarkers in monitoring the patients during hormonal treatment. Experimental Design: Serum procollagen type I N-terminal propeptide (PINP), bone-specific alkaline phosphatase (BAP), CTX-I, and YKL-40 were determined by ELISA in a longitudinal study of 106 patients with metastatic PC during treatment with total androgen ablation or parenteral estrogen. Serum samples were collected with 3 months interval. Median observation time was 4.9 years (range, 3.6-6.2). A total of 78 patients died (64 within 7 months following the last blood sampling). Results: After 6 months treatment, serum PINP, BAP, and YKL-40 decreased (P &amp;lt; 0.0001), but not serum CTX-I compared with baseline values. Univariate Cox analysis showed that serum PINP at 6 months [log transformed and treated as a continuous variable; hazard ratio (HR), 2.2; P &amp;lt; 0.0001], serum BAP (HR, 1.8; P &amp;lt; 0.0001), and serum CTX-I (HR, 2.4; P &amp;lt; 0.0001), but not serum YKL-40 (HR, 1.4; P = 0.16) were associated with survival. Multivariate Cox analysis including the biomarkers 6 months after the start of treatment showed that Soloway score (HR, 3.9; P = 0.013), WHO tumor grade (HR, 3.9; P = 0.004), and serum PINP (HR, 2.2; P &amp;lt; 0.0001) were independent prognostic variables of survival. Scoring the biomarkers during treatment as time-dependent covariates in univariate Cox regression analysis showed that increases in serum PINP (HR, 2.0; P &amp;lt; 0.0001), BAP (HR, 2.1; P &amp;lt; 0.0001), and YKL-40 (HR, 2.1; P &amp;lt; 0.0001) were predictors of early death. Conclusions: Serial monitoring of serum PINP, BAP, CTX-I, and YKL-40 in metastatic PC patients during hormonal treatment provided information of prognosis.
Pressure-volume curves in acute respiratory failure: automated low flow inflation versus occlusion.
Authors: G Servillo, C Svantesson, L Beydon, E Roupie, L Brochard, F Lemaire, B Jonson
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Pressure-volume (P-V) curves of the respiratory system allow determination of compliance and lower and upper inflection points (LIP and UIP, respectively). To minimize lung trauma in mechanical ventilation the tidal volume should be limited to the P-V range between LIP and UIP. An automated low flow inflation (ALFI) technique, using a computer-controlled Servo Ventilator 900C, was compared with a more conventional technique using a series of about 20 different inflated volumes (Pst-V curve). The pressure in the distal lung (Pdist) was calculated by subtraction of resistive pressure drop in connecting tubes and airways. Compliance (Cdist), Pdist(LIP), and Pdist(UIP) were derived from the Pdist-V curve and compared with Cst, Pst(LIP), and Pst(UIP) derived from the Pst-V curve. Nineteen sedated, paralyzed patients (10 with ARDS and 9 with ARF) were studied. We found: Cdist = 2.3 + 0.98 x Cst ml/cm H2O (r = 0.98); Pdist(LIP) = 0.013 + 1.09 x Pst(LIP) cm H2O (r = 0.96). In patients with ARDS: Pdist(UIP) = 4.71 + 0.84 x Pst(UIP) cm H2O (r = 0.94). In ARF, we found differences in UIP between the methods, but discrepancies occurred above tidal volumes and had little practical importance. They may reflect that Pdist comprises dynamic phenomena contributing to pressure in the distal lung at large volumes. Compliance, but not LIP and UIP, could be accurately determined without subtraction of resistive pressure from the pressure measured in the ventilator. We conclude that ALFI, which is fully automated and needing no ventilator disconnection, gives useful clinical information.
Imaging Angiogenesis: Applications and Potential for Drug Development
Authors: J. C. Miller, H. H. Pien, D. Sahani, A. G. Sorensen, J. H. Thrall
Journal: JNCI Journal of the National Cancer Institute (2005)

Recognition of the importance of angiogenesis to tumor growth and metastasis has led to efforts to develop new drugs that are targeted to angiogenic vasculature. Clinical trials of these agents are challenging, both because there is no agreed upon method of establishing the correct dosage for drugs whose mechanism of action is not primarily cytotoxic and because of the long time it takes to determine whether such drugs have a clinical effect. Therefore, there is a need for rapid and effective biomarkers to establish drug dosage and monitor clinical response. This review addresses the potential of imaging as a way to accurately and reliably assess changes in angiogenic vasculature in response to therapy. We describe the advantages and disadvantages of several imaging modalities, including positron emission tomography, x-ray computed tomography, magnetic resonance imaging, ultrasound, and optical imaging, for imaging angiogenic vasculature. We also discuss the analytic methods used to derive blood flow, blood volume, empirical semiquantitative hemodynamic parameters, and quantitative hemodynamic parameters from pharmacokinetic modeling. We examine the validity of these methods, citing studies that test correlations between data derived from imaging and data derived from other established methods, their reproducibility, and correlations between imaging-derived hemodynamic parameters and other pathologic indicators, such as microvessel density, pathology score, and disease outcome. Finally, we discuss which imaging methods are most likely to have the sensitivity and reliability required for monitoring responses to cancer therapy and describe ways in which imaging has been used in clinical trials to date.
Results of the Prospective Evaluation of Radial Keratotomy (PERK) Study 4 Years After Surgery for Myopia
Authors: George O. Waring
Journal: JAMA (1990)

The Prospective Evaluation of Radial Keratotomy Study is a nine-center clinical trial of a surgical technique to reduce simple myopia by making incisions in the cornea. There were 435 patients (one eye per patient is reported) enrolled in the study with a 91% follow-up rate at 4 years after surgery. After surgery, uncorrected visual acuity was 20/40 or better in 76% of eyes. Fifty-five percent of the eyes had a refractive error within ± 1.00 diopter; 28% were undercorrected, and 17% were overcorrected by more than 1.00 D. The width of the prediction 90% interval for the refractive change was 4.42 D, indicating a lack of predictability. The refractive error was not stable in some eyes; between 6 months and 4 years after surgery, 23% of eyes had a continued effect of the surgery of more than 1.00 D. For 323 patients with both eyes operated on, 64% stated they wore no optical correction. There were few serious complications. Eleven eyes (3%) lost two or three lines of best corrected visual acuity. Two eyes developed delayed bacterial keratitis without significant loss in best corrected visual acuity. (<i>JAMA</i>. 1990;263:1083-1091)
Intestinal metaplasia and the squamocolumnar junction: what does it all mean?
Authors: J E RICHTER
Journal: Gut (1998)

See article on page 659 

In theory, the diagnosis of Barrett’s oesophagus should be fairly simple, namely the presence of intestinal metaplasia anywhere in the tubular oesophagus. However, recognising where the tubular oesophagus ends and the saccular stomach begins is fraught with difficulty. The precise junction may be difficult to identify endoscopically because of the presence of a hiatus hernia, inflammation and some disassociation between the squamocolumnar junction and the lower oesophageal sphincter zone in normal individuals. Histologically, the squamous mucosa of the oesophagus accurately defines this area, but distinguishing normal gastric cardia and metaplastic changes of the distal oesophagus may be difficult. Normally, the mucosa of the cardia is composed of tightly packed mucus secreting glands with a lamina propria devoid of any significant inflammatory component. On occasion, biopsy specimens from the cardia show an increase in the amount of acute and chronic inflammatory cells, a condition termed carditis. The cardia can also have associated areas of intestinal metaplasia with goblet cells, histologically similar to the well described intestinal metaplasia in the distal stomach or classically defined as Barrett’s oesophagus when located in the tubular oesophagus. Finally, structures just do not sit still in the oesophagus during endoscopy, making precise location and biopsy even more difficult. Thus, it is difficult to know in every case whether the intestinal metaplasia is from the distal oesophagus or from the cardia.

The classic definition of Barrett’s oesophagus requiring the presence of at least …
α<sub>1</sub>-Antitrypsin Genotypes and the Acute-phase Response to Open Heart Surgery
Authors: ANDREW J. SANDFORD, TABASSUM CHAGANI, JOHN J. SPINELLI, PETER D. PARÉ
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

A mutation in the 3 ′ region of the α1-antitrypsin ( α1-AT) gene is associated with chronic obstructive pulmonary disease (COPD). However, the reason for this association is unknown. The mutation does not cause α1-AT deficiency but in vitro studies suggest it could attenuate the rise in α1-AT levels during the acute-phase response. Therefore, we sought an association between the 3 ′ mutation and a reduced rise in α1-AT levels following open heart surgery, a known trigger of the acute-phase response. We genotyped 198 patients and identified 31 with the 3 ′ mutation. Their α1-AT rise was compared with the remaining 167 wild type subjects. Multiple linear regression analysis identified sex, urgency of surgery, and surgical pump time as significant independent predictors of the rise in α1-AT. However, we found no association between the 3 ′ mutation and a reduced rise in α1-AT. We also identified patients who had the Z and S α1-AT deficiency mutations and found a significant reduction in the rise in α1-AT in individuals who were heterozygous for the Z mutation compared with wild type subjects. However, when the rise in α1-AT was expressed as a percentage of the basal level, there was no significant difference between individuals who had the S or Z mutations compared with wild type. Therefore, an attenuated α1-AT acute-phase response does not explain previous associations of the 3 ′ and S mutations with COPD. However, a deficient acute-phase rise in α1-AT may contribute to the susceptibility to COPD associated with the Z mutation.