tbuckley/cabot-search huggingface dataset:
Assessing the site of increased intestinal permeability in coeliac and inflammatory bowel disease.
Authors: K Teahon, S Somasundaram, T Smith, I Menzies, I Bjarnason
Journal: Gut (1996)

The precise site of intestinal permeability changes in patients with coeliac and inflammatory bowel disease is unknown.To design a non-invasive technique for the localisation of altered gastrointestinal permeability to 51chromium labelled EDTA (51CrEDTA). The method depends on comparing and defining concentration/time profiles in serum of a series of simultaneously ingested indicators with a well defined absorption site (3-0-methyl-D-glucose (jejunal indicator), 57cobalt labelled vitamin B12 (ileal indicator), and sulphasalazine (caecal-colonic indicator)) in relation to simultaneously ingested 51CrEDTA.Five normal controls, six patients with untreated coeliac disease, five with Crohn's ileitis, and five with pan-ulcerative colitis underwent study, which entailed the simultaneous ingestion of the above four test substances followed, during the next 24 hours, by timed serial collection of urine and serum for marker analysis.Urinary excretion of 51CrEDTA was significantly increased in all patient groups. Analysis of serum appearances and profiles of the markers suggested that the increased intestinal permeation of 51CrEDTA took place in the diseased jejunum in patients with coeliac disease, predominantly in the ileum in Crohn's disease and in the colon in the patients with pan-ulcerative colitis.A new non-invasive technique has been assessed that permits the localisation of the site of permeability changes with the gastrointestinal tract.
The hand eczema proteome: imbalance of epidermal barrier proteins
Authors: M. Lindberg
Journal: British Journal of Dermatology (2015)

Journal Article The hand eczema proteome: imbalance of epidermal barrier proteins Get access M. Lindberg M. Lindberg Department of Dermatology University Hospital Örebro Örebro 70185 Sweden Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 4, 1 April 2015, Pages 852–853, https://doi.org/10.1111/bjd.13579 Published: 01 April 2015
Risk Factors for Tuberculosis Infection in Sub-Saharan Africa
Authors: Christian Lienhardt, Katherine Fielding, Jackson Sillah, Abdulaye Tunkara, Simon Donkor, Kebba Manneh, David Warndorff, Keith P. McAdam, Steve Bennett
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Few studies have investigated the risk factors for tuberculosis (TB) infection in highly endemic countries. We conducted a household study in The Gambia, in which a tuberculin skin test (TST) was performed in members of the households of 315 smear-positive pulmonary TB cases and 305 community control subjects. The risk of being TST positive (10 mm or more) was higher in contacts of cases than in contacts of control subjects. It increased with age, male sex, and duration of stay in the household but was not associated with the presence of a bacille de Calmette-Guérin scar. Within the households of the TB cases, the risk of TST positivity was higher in males and was increased with age, social proximity to the case, and the radiologic extent of the disease in the case's chest X-ray. Adjusting on these, the risk of TST positivity was higher in first-degree relatives compared with more distant relatives and nongenetically related household members, but the effect was not statistically significant. In highly endemic areas, the risk of TB infection in contacts of TB infectious cases is associated with age, sex, intensity of exposure to the case, and severity of disease in the case, but it is possible that genetic factors contribute to the susceptibility to Mycobacterium tuberculosis infection.
Phase I and Pharmacokinetic Study of Imatinib Mesylate (Gleevec) and Gemcitabine in Patients with Refractory Solid Tumors
Authors: Yaqoob Ali, Yong Lin, Mecide M. Gharibo, Murugesan K. Gounder, Mark N. Stein, Theodore F. Lagattuta, Merrill J. Egorin, Eric H. Rubin, Elizabeth A. Poplin
Journal: Clinical Cancer Research (2007)

Preclinical data shows improvements in response for the combination of imatinib mesylate (IM, Gleevec) and gemcitabine (GEM) therapy compared with GEM alone. Our goals were to determine the maximum tolerated dose of GEM and IM in combination, the pharmacokinetics of GEM in the absence and in the presence of IM, and IM pharmacokinetics in this combination.Patients with refractory malignancy, intact intestinal absorption, measurable/evaluable disease, adequate organ function, Eastern Cooperative Oncology Group PS 0-2, and signed informed consent were eligible. Initially, treatment consisted of 600 mg/m2 of GEM (10 mg/m2/min) on days 1, 8, and 15, and 300 mg of IM daily every 28 days. Due to excessive toxicity, the schedule was altered to IM on days 1 to 5 and 8 to 12, and GEM on days 3 and 10 every 21 days. Two final cohorts received IM on days 1 to 5, 8 to 12, and 15 to 19.Fifty-four patients were treated. IM and GEM given daily at 500 to 600 mg/m2 on days 1, 8, and 15 produced frequent dose-limiting toxicities. With the modified scheduling, GEM given at 1,500 mg/m2/150 min was deliverable, along with 400 mg of IM, without dose-limiting toxicities. Three partial (laryngeal, renal, and mesothelioma) and two minor (renal and pancreatic) responses were noted at GEM doses of 450 to 1,500 mg/m2. Stable disease >24 weeks was seen in 17 patients. CA19-9 in 7 of 10 patients with pancreatic cancer was reduced by approximately 90%. IM did not significantly alter GEM pharmacokinetics.The addition of intermittently dosed IM to GEM at low to full dose was associated with broad antitumor activity and little increase in toxicity.
Pharmacological Modulation of Sarcoplasmic Reticulum Function in Smooth Muscle
Authors: Régent Laporte, Adrian Hui, Ismail Laher
Journal: Pharmacological Reviews (2004)

The sarco/endoplasmic reticulum (SR/ER) is the primary storage and release site of intracellular calcium (Ca<sup>2+</sup>) in many excitable cells. The SR is a tubular network, which in smooth muscle (SM) cells distributes close to cellular periphery (superficial SR) and in deeper aspects of the cell (deep SR). Recent attention has focused on the regulation of cell function by the superficial SR, which can act as a buffer and also as a regulator of membrane channels and transporters. Ca<sup>2+</sup> is released from the SR via two types of ionic channels [ryanodine- and inositol 1,4,5-trisphosphate-gated], whereas accumulation from thecytoplasm occurs exclusively by an energy-dependent sarco-endoplasmic reticulum Ca<sup>2+</sup>-ATPase pump (SERCA). Within the SR, Ca<sup>2+</sup> is bound to various storage proteins. Emerging evidence also suggests that the perinuclear portion of the SR may play an important role in nuclear transcription. In this review, we detail the pharmacology of agents that alter the functions of Ca<sup>2+</sup> release channels and of SERCA. We describe their use and selectivity and indicate the concentrations used in investigating various SM preparations. Important aspects of cell regulation and excitation-contractile activity coupling in SM have been uncovered through the use of such activators and inhibitors of processes that determine SR function. Likewise, they were instrumental in the recent finding of an interaction of the SR with other cellular organelles such as mitochondria. Thus, an appreciation of the pharmacology and selectivity of agents that interfere with SR function in SM has greatly assisted in unveiling the multifaceted nature of the SR.
NF-κB, and not MYCN, Regulates MHC Class I and Endoplasmic Reticulum Aminopeptidases in Human Neuroblastoma Cells
Authors: Matteo Forloni, Sonia Albini, Maria Zaira Limongi, Loredana Cifaldi, Renata Boldrini, Maria Rita Nicotra, Giuseppe Giannini, Pier Giorgio Natali, Patrizio Giacomini, Doriana Fruci
Journal: Cancer Research (2010)

Abstract Neuroblastoma (NB) is the most common solid extracranial cancer of childhood. Amplification and overexpression of the MYCN oncogene characterize the most aggressive forms and are believed to severely downregulate MHC class I molecules by transcriptional inhibition of the p50 NF-κB subunit. In this study, we found that in human NB cell lines, high MYCN expression is not responsible for low MHC class I expression because neither transfection-mediated overexpression nor small interfering RNA suppression of MYCN affects MHC class I and p50 levels. Furthermore, we identified NF-κB as the immediate upstream regulator of MHC class I because the p65 NF-κB subunit binds MHC class I promoter in chromatin immunoprecipitation experiments, and MHC class I expression is enhanced by p65 transfection and reduced by (a) the chemical NF-κB inhibitor sulfasalazine, (b) a dominant-negative IKBα gene, and (c) p65 silencing. Moreover, we showed that the endoplasmic reticulum aminopeptidases ERAP1 and ERAP2, which generate MHC class I binding peptides, are regulated by NF-κB, contain functional NF-κB–binding elements in their promoters, and mimic MHC class I molecules in the expression pattern. Consistent with these findings, nuclear p65 was detected in NB cells that express MHC class I molecules in human NB specimens. Thus, the coordinated downregulation of MHC class I, ERAP1, and ERAP2 in aggressive NB cells is attributable to a low transcriptional availability of NF-κB, possibly due to an unknown suppressor other than MYCN. Cancer Res; 70(3); 916–24
Impact of shunt surgery for variceal bleeding in the natural history of ascites in cirrhosis: A retrospective study
Authors: Antoni Castells, Joan Saló, Ramon Planas, Juan Carlos Quer, Angels Ginès, Jaume Boix, Pere Ginès, Miquel Angel Gassull, Josep Terés, Vicente Arroyo, Joan Rodés
Journal: Hepatology (1994)

Despite the efficacy of shunt surgery in the treatment of variceal bleeding, less effective nonoperative therapies are being substituted because surgical shunt does not modify survival and increases hepatic encephalopathy. However, the real impact of shunt surgery on the natural history of ascites and its complications has not been established. The course of 204 Child-Pugh A and B cirrhotic patients with variceal bleeding included in three controlled trials of our units who survived first hospitalization was updated. Ninety-eight patients (group I) were treated by portacaval (56 patients) or distal splenorenal (42 patients) shunt, whereas 106 (group II) were treated by nonshunt procedures (sclerotherapy in 89 patients and staple transection in 17 patients). As expected, the 5-yr probability of variceal rebleeding was lower (13% vs. 44%) and hepatic encephalopathy higher (50% vs. 28%) in group I than in group II, and survival was similar (67% vs. 60%). Shunt surgery had a great impact on the natural history of ascites and its complications. The probability of occurrence of ascites (15% vs. 73%; p < 0.0001), spontaneous bacterial peritonitis (2% vs. 21%; p < 0.0001) and hepatorenal syndrome (4% vs. 21%; p < 0.01) was greatly reduced. These beneficial effects accounted for the lower percentage patients requiring readmissions (51% vs. 70%; p = 0.02) and shorter total time spent in hospital (14 +/- 22 vs. 26 +/- 39 days/patient; p = 0.01) in group I. These data indicate that shunt surgery, in addition to reducing the probability of rebleeding, markedly decreases the probability of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome development.(ABSTRACT TRUNCATED AT 250 WORDS)
Lifting the screen on <i>Neural organization:</i> Is computational functional modeling necessary?
Authors: Damian Keil, Keith Davids
Journal: Behavioral and Brain Sciences (2000)

Arbib et al.'s comprehensive review of neural organization, over-relies on modernist concepts and restricts our understanding of brain and behavior. Reliance on terms like coding, transformation, and representation perpetuates a “black-box approach” to the study of the brain. Recognition is due to the authors for attempting to introduce postmodern concepts such as chaos and self-organization to the study of neural organization. However, confusion occurs in the implementation of “biologically rooted” schema theory in which schemas are viewed as computer programs. The inclusion of an additional functional level between structure and dynamics is unnecessary in a postmodernist perspective of brain and behavior.
Rhizomelic chondrodysplasia punctata. Deficiency of 3-oxoacyl-coenzyme A thiolase in peroxisomes and impaired processing of the enzyme.
Authors: J C Heikoop, C W van Roermund, W W Just, R Ofman, R B Schutgens, H S Heymans, R J Wanders, J M Tager
Journal: Journal of Clinical Investigation (1990)

The rhizomelic form of chondrodysplasia punctata (RCDP) is a peroxisomal disorder characterized biochemically by an impairment of plasmalogen biosynthesis and phytanate catabolism. We have now found that the maturation of peroxisomal 3-oxoacyl-CoA thiolase is impaired in fibroblasts from RCDP patients. To establish the subcellular localization of the 3-oxoacyl-CoA thiolase precursor protein, cultured skin fibroblasts were fractionated on a continuous Nycodenz gradient. Only a small amount of 3-oxoacyl-CoA thiolase activity was present in the catalase-containing (peroxisomal) fractions of RCDP fibroblasts in comparison with control fibroblasts. Moreover, the amount of thiolase protein in immunoblots of the catalase-containing fractions was below the limit of detection. Finally, the beta-oxidation of [14C]palmitoyl-CoA was found to be reduced in these fractions. We conclude that the mutation in RCDP leads to a partial deficiency of 3-oxoacyl-CoA thiolase activity in the peroxisomes and, concomitantly, an impairment in the ability to convert the precursor of this protein to the mature form. The reduction of 3-oxoacyl-CoA thiolase activity results in a decrease in the rate of peroxisomal beta-oxidation of palmitoyl-CoA. However, the capacity of the peroxisomes to oxidize very-long-chain fatty acids must be sufficient to prevent excessive accumulation of these compounds in vivo.
Genetics of susceptibility for radiation-induced leukemia. Mapping of genes involved to chromosomes 1, 2, and 4, and implications for a viral etiology in the disease.
Authors: D Meruelo, M Offer, N Flieger
Journal: The Journal of Experimental Medicine (1981)

Susceptibility to radiation-induced leukemia in (A/J x B10)F2 mice is encoded for by genes in chromosomes 1, 2, and 4. The loci involved in chromosomes 1 and 4 are close to or similar to xenotropic virus inducibility locus on chromosome 1 and a locus-affecting expression of xenotropic MuLV envelope-related cell surface antigens. Radiation-induced leukemia-1 (Ril-1) on chromosome 2 plays an overriding influence in susceptibility to the disease. This locus might encode ecotropic viral-associated genetic information or might contain cellular sequences with oncogenic potential. These findings are of interest in view of the importance of recombinant viruses to leukemogenesis. Furthermore, it is intriguing that Ril-1 is located in a chromosomal site rich in thymus differentiation-specific loci. An explanation for tissue-specific activation of endogenous viruses is that activation of the virus in question is dependent on differentiation-specific steps.
Controversies old and new
Authors: Victor W Nitti, Herbert Lepor
Journal: The Lancet (1995)

The most significant contributions to the urological literature in 1995 were in areas of former or continued controversy. Several of these controversial topics have the potential to have an immediate impact on decisions about patient-care decisions. In the area of urinary stone management, Grasso showed that uncomplicated ureteral calculi were treated most cost effectively with endoscopic techniques as opposed to extracorporeal shock-wave lithotripsy (ESWL). While the authors acknowledged that ESWL remains the treatment of choice for most renal calculi, they questioned its cost-effectiveness in treating ureteral calculi. In female urology, Trockman reported the first long-term results (average 9.8 years, range 5-13) of the modified Pereyra bladder-neck suspension for the treatment of stress urinary incontinence. Using questionnaires and outcome analysis, they observed a significantly lower success rate--only a 49% cure of stress incontinence--than with previous studies. Nevertheless, 72% of women were satisfied with the results of surgery. Although questionnaires may eliminate some of the bias introduced by the physician-patient relationship, they also preclude objective physician assessment. In the area of urodynamics, several studies, including one by Yalla confirmed that lower-urinary-tract symptoms associated with benign prostatic hyperplasia (BPH) do not correlate with the presence of urodynamically proven bladderoutlet obstruction. A controversial topic in urology has been the early detection and diagnosis of prostate cancer. Opponents of screening claim that the disease will be overdiagnosed, as most patients will die with, and not of, the disease. Two important articles on the natural history of prostate cancer fuelled the debate concerning early detection of prostate cancer and seem to support early detection. Aus showed that there is a significant risk of dying from localised (non-metastatic) prostate cancer if the disease is not treated with curative intent. They specifically looked at the subgroup of patients without evidence of metastases at diagnosis (M0). The mortality rate due to prostate cancer in this group was 50%. However, M0 patients who lived at least 10 years from the time of diagnosis had an even higher prostate cancer mortality of 63%. Also, as the age at diagnosis decreased, the likelihood of dying from prostate cancer increased. All patients diagnosed at age 55 or less died from the disease. This report was a contradiction of earlier reports with shorter duration of follow-up in older subjects that suggested a significantly lower risk of dying from localised prostate cancer. One of the key factors in the study by Aus seems to be that longer
Response to Letter Regarding Article, “Association Between Aneurysm Shoulder Stress and Abdominal Aortic Aneurysm Expansion: A Longitudinal Follow-Up Study”
Authors: Zhi-Yong Li, Tjun Y. Tang, Jean U-King-Im, David J. Bowden, Umar Sadat, Jonathan H. Gillard, Paul D. Hayes
Journal: Circulation (2011)
Associations between different forms of gastro-oesophageal reflux disease
Authors: H B El-Serag, A Sonnenberg
Journal: Gut (1997)

A bstract Aims —To study the epidemiology and natural history of gastro-oesophageal reflux disease (GORD). Methods —Retrospective cohort study involving all 172 hospitals of the Department of Veterans Affairs. A total of 194 527 patients with GORD were followed between 1981 and 1994. Distribution of oesophagitis, oesophageal ulcer, oesophageal stricture, strictured hiatus hernia, hiatus hernia, and pyrosis by age, sex, and ethnicity were determined. The comorbid occurrence of various forms of GORD in identical patients was analysed by an age and race standardised morbidity ratio. The population of all hospitalised veterans was used for comparison. Results —Severe forms of GORD associated with oesophageal erosions, ulcers, or strictures, affected elderly, white, male patients more often than their corresponding opposite demographic group. All forms of GORD clustered in the same patient population; on average, any form of GORD was 10 times more likely to occur in a patient with another form of GORD than without. The highest morbidity ratio (22) was found in oesophageal ulcer and stricture. About one third of all patients with oesophageal erosions, ulcers, or strictures also had hiatus hernia; 46% of patients with hiatus hernia were diagnosed as having other forms of GORD. While one third of all oesophageal strictures appeared in patients without other forms of GORD diagnosed at any time, oesophageal ulcers were always associated with some other form of GORD. No clear cut progression in different forms of GORD was found. Conclusions —Older age, male sex, and white ethnicity are risk factors in the development of severe forms of GORD. The most severe grade of GORD is reached at the onset of the disease.
Osteopontin and β <sub>3</sub> Integrin Are Coordinately Expressed in Regenerating Endothelium In Vivo and Stimulate Arg-Gly-Asp–Dependent Endothelial Migration In Vitro
Authors: Lucy Liaw, Volkhard Lindner, Stephen M. Schwartz, Ann F. Chambers, Cecilia M. Giachelli
Journal: Circulation Research (1995)

Abstract Osteopontin is an Arg-Gly-Asp (RGD)–containing acidic glycoprotein postulated to mediate cellular adhesion and migration in a growing number of normal and pathological conditions through interaction with integrin molecules. In this report, we have investigated the potential contributions of osteopontin and one of its receptors, the α v β 3 integrin, to endothelial regenerative processes by using both in vivo and in vitro models. In vivo, uninjured rat arterial endothelium had undetectable levels of osteopontin and β 3 -integrin mRNA by in situ hybridization. After balloon catheter denudation, osteopontin mRNA levels correlated temporally and spatially with active endothelial proliferation and migration, with the highest levels observed at the wound edge between 8 hours and 2 weeks after injury, declining to uninjured levels at 6 weeks, when regeneration was complete. Osteopontin protein levels, as determined by immunocytochemistry, paralleled the time course of mRNA expression. Likewise, β 3 -integrin mRNA and protein levels were substantially elevated in regenerating endothelial cells but were not detectable in uninjured or healed endothelium. In vitro, rat smooth muscle cell–derived and bacterial expressed mouse recombinant osteopontins both stimulated the adhesion and directed migration of bovine aortic endothelial cells through interactions with the α v β 3 receptor. Structural mutants of osteopontin confirmed the importance of the RGD domain for both adhesion and migration of endothelial cells through α v β 3 . These data suggest important roles for osteopontin and β 3 integrin in regenerating endothelium.