tbuckley/cabot-search huggingface dataset:
Medium and long chain fat absorption in patients with cirrhosis.
Authors: W G Linscheer, J F Patterson, E W Moore, R J Clermont, S J Robins, T C Chalmers
Journal: Journal of Clinical Investigation (1966)

Medium chain fatty acids (MCFA) are known to differ from long chain fatty acids (LCFA) in their absorption, transportation, and metabolism.In malabsorption states, medium chain triglycer- ides (MCT) are better absorbed than long chain triglycerides (LCT) (1-3) and have been used in the treatment of such conditions.MCFA are trans- ported from the gut mainly by the portal vein as fatty acids, whereas LCFA are transported pri- marily by the lymphatics in chylomicrons (4-6).Absorbed MCFA are immediately oxidized in the liver, as demonstrated by 14CO2 recovery in the expired air of normal volunteers who have received orally administered 14C-labeled MCFA (7-9).Intestinal absorption, transport, and hepatic clearance of MCFA in patients with cirrhosis are of interest for two reasons: 1) Fat malabsorption sufficient to contribute to malnutrition is common in cirrhosis ( 10,11 ), and information about the ab- sorption of medium chain fats is lacking.2) Por- tacaval shunting of blood and a variable diminution in the capacity of the cirrhotic liver to metabolize MCFA emphasized the need for study of periph- eral blood levels after their administration.
Interruption of CD28-mediated costimulation during allergen challenge protects mice from allergic airway disease
Authors: Tea Gogishvili, Fred Lühder, Frank Kirstein, Natalie E. Nieuwenhuizen, Sandra Goebbels, Sandra Beer-Hammer, Klaus Pfeffer, Sebastian Reuter, Christian Taube, Frank Brombacher, Thomas Hünig
Journal: Journal of Allergy and Clinical Immunology (2012)
TREK-1 Is a Novel Molecular Target in Prostate Cancer
Authors: Iryna Voloshyna, Alessandra Besana, Mireia Castillo, Tulio Matos, I. Bernard Weinstein, Mahesh Mansukhani, Richard B. Robinson, Carlos Cordon-Cardo, Steven J. Feinmark
Journal: Cancer Research (2008)

Abstract TREK-1 is a two-pore domain (K2P) potassium channel that carries a leak current that is time- and voltage-independent. Recently, potassium channels have been related to cell proliferation and some K2P family channels, such as TASK-3, have been shown to be overexpressed in specific neoplasms. In this study, we addressed the expression of TREK-1 in prostatic tissues and cell lines, and we have found that this potassium channel is highly expressed in prostate cancer but is not expressed in normal prostate nor in benign prostatic hyperplasia. Furthermore, expression of TREK-1 correlates strongly with the grade and the stage of the disease, suggesting a causal link between channel expression and abnormal cell proliferation. In vitro studies showed that TREK-1 is highly expressed in PC3 and LNCaP prostate cancer cell lines but is not detectable in normal prostate epithelial cells (NPE). In this report, we show that overexpression of TREK-1 in NPE and Chinese hamster ovary (CHO) cells leads to a significant increase in proliferation. Moreover, the increased cell proliferation rate of PC3 cells and TREK-1 overexpressing CHO cells could be reduced when TREK-1 current was reduced by overexpression of a dominant-negative TREK-1 mutant or when cells were exposed to a TREK-1 inhibitor. Taken together, these data suggest that TREK-1 expression is associated with abnormal cell proliferation and may be a novel marker for and a molecular target in prostate cancer. [Cancer Res 2008;68(4):1197–203]
Mechanism of Triamterene-Induced Megaloblastosis
Authors: JOSÉ CORCINO
Journal: Annals of Internal Medicine (1970)

A patient with cirrhosis of the liver who developed megaloblastosis despite normal serum and red cell folate levels after receiving conventional doses of triamterene for 2 weeks is described. Studies using short-term human bone marrow cultures indicate that triamterene interferes with the de novo deoxyribonucleic-acid-thymine synthesis from deoxyuridine and that this interference is completely corrected by reduced (folinic acid) but only partially by oxidized (pteroylglutamic acid) folate. These findings support the concept that triamterene inhibits dihydrofolate reductase activity in human bone marrow, as it does in other mammalian systems, and suggest this drug should be used with caution in patients who may have borderline folate stores (such as pregnant women and alcoholics).
Unusual inflammatory and hyperkeratotic halo naevus in children
Authors: A. Patrizi, I. Neri, E. Sabattini, L. Rizzoli, C. Misciali
Journal: British Journal of Dermatology (2005)

Although the classic halo naevus (HN) is a melanocytic naevus with a surrounding rim of depigmentation, these naevi can present unusual features. We describe an unusual and previously unreported variety of HN in children. Between March 1999 and September 2002, 14 children (11 boys and three girls, age range 6–14 years) were referred to us for evaluation of one or more 'inflamed' naevi. All the affected naevi showed the same clinical development: (i) after an initial inflammatory stage their surfaces gradually became thickened and rough, then (ii) verrucous and raised, and finally (iii) scaly crusted. A marked halo of depigmentation subsequently developed in all lesions, with simultaneous disappearance of the hyperkeratotic surface appearance. Lesions were multiple in five cases and single in nine, and were mainly located on the back (nine cases). Excisional biopsy was performed in eight cases. The biopsies were all taken in the 'prehalo phase'. In each case, histopathology revealed a compound melanocytic naevus, with additional features that varied depending on the clinical stage of the lesion. Immunohistochemical staining of the dense inflammatory infiltrate showed a predominance of CD3+/CD8+ T lymphocytes, as usually occurs in HN. On the basis of these observations, we believe that the described naevi represent an unusual variety of HN in children. Knowledge of this possible clinical evolution of HN is important to avoid unnecessary surgical excision in these young patients.
Keratitis?ichthyosis?deafness syndrome: disease expression and spectrum of connexin 26 (GJB2) mutations in 14 patients
Authors: J. Mazereeuw-Hautier, E. Bitoun, J. Chevrant-Breton, S.Y.K. Man, C. Bodemer, C. Prins, C. Antille, J.-H. Saurat, D. Atherton, J.I. Harper, D.P. Kelsell, A. Hovnanian
Journal: British Journal of Dermatology (2007)

Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital disorder characterized by the association of skin lesions, hearing loss and vascularizing keratitis. KID syndrome is caused by autosomal dominant mutations in the connexin 26 gene (GJB2).To establish whether there is a correlation between genotype and phenotype in KID syndrome.Clinical examination and molecular analysis of GJB2 were performed in a cohort of 14 patients with KID syndrome originating from 11 families. We also reviewed the 23 cases with molecular analysis previously reported in the literature.The patients displayed the classical signs of KID syndrome with the additional finding of inflammatory nodules in six patients (43%); this clinical finding has not been described previously in the literature. One patient presented at the age of 18 years with a fatal carcinoma of the tongue, an extremely rare reported complication. For seven of the 11 families (64%) the disease was sporadic, whereas it was familial in the remaining four families (36%). Twelve patients (86%) were heterozygous for the p.Asp50Asn mutation and two patients (14%) were heterozygous for the p.Ser17Phe mutation. Surprisingly, a family in which we personally examined the healthy parents had two affected children heterozygous for the p.Asp50Asn mutation, suggesting germinal mosaicism. Compared with patients with the p.Asp50Asn mutation, the two patients with the p.Ser17Phe mutation had more severe skin involvement. One of these two patients experienced a carcinoma of the tongue.Familial cases appear to be more frequent than reported in the literature. The possibility of germinal mosaicism must be taken into account for genetic counselling. This study also suggests that patients with the p.Ser17Phe mutation may have a more severe phenotype and could be at higher risk for tongue carcinoma.
A Non-Gastrin Secretogogue in Ulcerogenic Tumors of the Pancreas
Authors: WILLIAM Y. CHEY
Journal: Annals of Internal Medicine (1984)

In 18 patients with hypersecretion of acid, severe ulcer diathesis, and pancreatic islet cell tumor or hyperplasia, 14 had hypergastrinemia and 4 had normal plasma gastrin concentration. The neoplasms contained several gut peptides beside gastrin. The immunoreactive gastrin in the tumor extracts measured less than 7 ng/g, less than the amount previously reported. The extracts of each patient's tumor also contained a secretogogue other than gastrin that stimulated gastric acid secretion in rats. In addition, the plasma extracts of 2 patients also contained a secretogogue that stimulated acid secretion. After surgical resection of a recurrent metastatic tumor in 1 patient, basal acid secretion decreased from 13.9 to less than 1 meq/h, and the bioactivity of the plasma disappeared. These observations suggest the existence of a secretogogue that appears to be a protein in the pancreatic tumors of some patients with severe ulcer diathesis and hypersecretion.
Abstract LB-149: The OPCML tumor suppressor binds and negatively regulates the Axl receptor tyrosine kinase, sensitizing cells to foretinib in epithelial ovarian cancer (EOC)
Authors: Sushmita Roy Nawathe, Elisa Zanini, Giles Hayward, Arthur B. McKie, Hani Gabra
Journal: Cancer Research (2012)

Abstract OPCML (opioid binding protein/cell adhesion like molecule) is a tumour suppressor gene that is silenced almost by somatic methylation in more than 80% of EOC cases, with loss of heterozygosity (LOH) occurring in 49% of cases [1,2]. OPCML binds a specific repertoire of receptor tyrosine kinases (RTKs) consisting of HER2, HER4 EphA2, FGFR1 and FGFR3. OPCML switches RTKs from clathrin to non clathrin dependent endocytosis, resulting in polyubiquitination of the RTK and targeting to the proteasome for destruction with associated signalling and growth inhibition [3]. We show that Axl, a TAM family RTK that is frequently activated in ovarian cancer [4], also interacts with and is downregulated by OPCML. Axl is downregulated following transient and stable OPCML expression in ovarian cancer lines SKOV3 and PEO1, with reciprocally increased Axl expression following stable knockdown of physiological OPCML in normal ovarian surface epithelial line OSE-C2. We performed co-IP and mammalian 2-hybrid (M 2-H) analysis between Axl and OPCML and determined that the Ig and FNIII domains are crucial to this interaction. We previously reported a complete loss of function proline 95 to arginine mutation [2]. Transfection of OPCMLWT protein in OPCML deficient cells promotes intercellular adhesion and adhesion to Collagen I and Fibronectin matrix, in association with Axl downregulation, In contrast OPCMLP95R transfection did not repress Axl and did not promote intercellular or cell to matrix adhesion. M 2-H data demonstrated that OPCMLP95R expression abolishes the interaction seen between OPCMLWT and Axl. We explored the impact of OPCML expression on cell signalling response to Foretinib (GSK1363089), a potent inhibitor of Axl [5]; OPCML led to a 3-fold sensitization to the tyrosine kinase inhibitor. The finding that OPCML, a frequently inactivated ovarian cancer tumor suppressor negatively regulates Axl, a frequently activated RTK in ovarian cancer and sensitises Axl positive OPCML deficient cells to Foretinib defines a promising predictive and therapeutic role for OPCML in ovarian cancer. References 1. Gabra et al (1996) Cancer Res 56: 950-954. 2. Sellar et al (2003) Nat Genet 34: 337-343. 3. McKie et al (Feb2012) Cancer Discovery (in press). 4. Rankin et al (2010) Cancer Res 70: 7570-7578 5. Liu et al. (2009) Cancer Res 69: 6871-6878. 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 LB-149. doi:1538-7445.AM2012-LB-149
The induction of macrophage spreading by factor B of the properdin system.
Authors: O Götze, C Bianco, Z A Cohn
Journal: The Journal of Experimental Medicine (1979)

Unstimulated mouse peritoneal macrophages attached to a glass substratum responded to activated human factor B (Bb) of the properdin system but not to native factor B with rapid spreading and a concomitant increase in their apparent surface area. Excellent correlation of the distribution of Bb protein and cell-spreading activity was found upon purification of Bb by ion-exchange and molecular seive chromatography and alkaline polyacrylamide gel electrophoresis. 1.6 microgram of purified Bb was sufficient to induce spreading in 50% of 5 x 10(4) glass attached macrophages within 1-2 h at 37 degrees C. Treatment of Bb with di-isopropyl-fluorophosphate indicated that the intact catalytic site of the serine-proteinase Bb was required for the initiation of macrophage spreading. The involvement of factor B in the induction of rapid cell spreading could also be indirectly demonstrated in an autologous system in which F(ab')2 fragments of an antiserum to mouse B prevented mouse macrophages from spreading in response to complement-activated mouse serum. These experiments suggest a role for factor B and the alternative pathway of complement fixation in the localization of mononuclear phagocytes to areas of inflammation.
Stenosis Following Tracheostomy for Respiratory Care
Authors: Bennie Geffin
Journal: JAMA (1971)

Thirty-two patients with symptomatic tracheal deformity following ventilatory assistance through cuffed tracheal tubes have been treated during a seven-year period. The diagnosis is strongly suggested by symptoms of upper-airway obstruction following decannulation. Radiologic studies and bronchoscopy are invaluable diagnostic adjuncts. The lesions may consist of deformity of anterior wall or stenosis at the tracheostomy site, or more typically, of circumferential stenotic lesions at the level of the inflatable cuff. Tracheomalacia also occurs. The etiology appears primarily to be pressure necrosis caused by the rigidly inflated cuff, with subsequent cicatrization. Resection of the stenosis and primary reconstruction of the trachea is the definitive treatment of choice, as results are generally good. Dilatation and stenting are usually of temporary values only. In a small number of patients, permanent tracheostomy must be accepted.
Danish sperm donor passed neurofibromatosis on to five children
Authors: A. Hansen
Journal: BMJ (2012)

Danish health authorities are expected to restrict regulations regarding sperm donation after a donor was found to have passed on the genetic disease neurofibromatosis to at least five children he fathered.

The donor donated his sperm to the Copenhagen based sperm bank Nordisk Cryobank, which did not screen for the genetic disorder. The sperm were subsequently used by several different fertility clinics. According to the Danish broadcasting corporation (DR), the man has fathered 43 children in 14 different in vitro fertilisation (IVF) clinics. 

The clinics are located not only in Denmark but also in Sweden, Norway, …
Efficacy of topical sensitizers in the treatment of alopecia areata
Authors: Cameron K. Rokhsar, Jerome L. Shupack, Jonothan J. Vafai*, Ken Washenik
Journal: Journal of the American Academy of Dermatology (1998)

It has been more than 2 decades since the first report of the use of dinitrochlorobenzene to induce hair growth in 2 patients with alopecia areata. Other topical sensitizers, namely squaric acid dibutylester and diphenylcyclopropenone, have been used with variable success. This article reviews the efficacy and safety of the use of topical sensitizers in the treatment of alopecia areata. (J Am Acad Dermatol 1998;39:751-61.)
Polymorphisms for aromatic amine metabolism in humans: relevance for human carcinogenesis.
Authors: F F Kadlubar, M A Butler, K R Kaderlik, H C Chou, N P Lang
Journal: Environmental Health Perspectives (1992)

The metabolic pathways associated with carcinogenic aromatic amines in humans provide an excellent example of polymorphisms that appear to be relevant to human carcinogenesis. In this regard, the N-acetylation of arylamines and the O-acetylation of their N-hydroxy metabolites are catalyzed preferentially by a genetically polymorphic acetyltransferase, high activity of which has been correlated with decreased risk for urinary bladder cancer and increased susceptibility to colorectal cancer. Cytochrome P450IA2, the principal liver enzyme involved in aromatic amine N-oxidation, exhibits a wide interindividual variation that appears trimodal in several populations and is clearly inducible by cigarette smoking and probably other host factors as well. UDP-Glucuronosyltransferases, which catalyze the N-glucuronidation of N-hydroxyarylamines and are likely to be responsible for their transport to the colon, show widely varied but unimodal distributions in humans. In contrast, human liver sulfotransferase activity for N-hydroxyarylamines, which would be expected to decrease their transport through the circulation, is catalyzed by a polymorphic enzyme(s) that is expressed at higher levels in blacks, as compared to whites, and could contribute to their relatively lower incidence of urinary bladder cancer. Peroxidative activation of aromatic amines can also occur, especially from prostaglandin H synthase in the urinary bladder and myeloperoxidase in the lungs of cigarette smokers, and both show considerable individual variability, apparently due to the extent of tissue inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)
Annual tobacco deaths in poor countries to reach 7 million by 2030
Authors: Roger Dobson
Journal: BMJ (2004)

The rapid rise in smoking in many developing countries will have devastating consequences, a new report says.

By 2030, the number of deaths resulting from tobacco use will reach 7 million a year in the developing world, the authors of a review in Thorax have estimated (2004;59:623-30).

International support is essential to reverse the rise, say the authors, but they cite a range of obstacles, including high smoking rates among doctors and other health professionals, lack of awareness of the dangers of tobacco, economic dependence on tobacco, poor healthcare systems, …
Fishing with the wrong nets: How the implicit slips through the Representational Theory of Mind
Authors: Luis Jiménez, Axel Cleeremans
Journal: Behavioral and Brain Sciences (1999)

Dienes &amp; Perner's target article is not a satisfactory theory of implicit knowledge because in endorsing the representational theory of knowledge, the authors also inadvertently accept that only explicit knowledge can be causally efficacious, and hence that implicit knowledge is an inert category. This conflation between causal efficacy, knowledge, and explicitness is made clear through the authors' strategy, which consists of attributing any observable effect to the existence of representations that are as minimally explicit as needed to account for behavior. In contrast, we believe that causally efficacious and fully implicit knowledge exists, and is best embodied in frameworks that depart radically from classical assumptions.
120 A 7 GENE SET ASSOCIATED WITH CHRONIC HYPOXIA OF UNIVERSAL PROGNOSTIC IMPORTANCE IN HEPATOCELLULAR CARCINOMA
Authors: H. van Malenstein, O. Gevaert, L. Libbrecht, A. Daemen, J. Allemeersch, F. Nevens, E. Van Cutsem, D. Cassiman, B. De Moor, C. Verslype, J. van Pelt
Journal: Journal of Hepatology (2010)
Biochemical Studies in Full-Blooded Navajo Indians
Authors: ROBERT J. KOSITCHEK, MOSES WURM, REUBEN STRAUS
Journal: Circulation (1961)

The beta/alpha lipoprotein ratio and other serum lipid components have been studied in a population of full-blooded Navajo Indians. The findings offer a basis for assessing the low degree of atherogenesis and are consistent with evidence for the low incidence of coronary heart disease in this ethnic group.
Medical statistics in postgraduate examinations
Authors: K. McPherson
Journal: BMJ (1982)

noted, however, during pregnancy and in the postpartum period among women with preexisting Graves's disease.'In a recent study2 a transient disturbance of thyroid function was found in 27 (5-3%) of 503 women, three to eight months following delivery; permanent hypothyroidism occurred in one (0 19%).Thus, while control of hyperthyroidism during pregnancy is no more difficult to achieve than in the non-pregnant state, pregnancy does have profound effects on underlying autoimmune phenomena.
P13. Intra-tumoral and surrogate immune responses in patients treated with the engineered anti-PD-L1 antibody (MPDL3280A)
Authors: M Kowanetz, MT Vu, J Wu, H Koeppen, H Kohrt, S Gettinger, C Cruz, M Denker, DS Chen, P Hegde
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts PD-L1 regulates CD8 T cell/Th1 immune responses. PD-L1 expressed in the tumor microenvironment can bind to PD-1 or B7.1 on activated T cells and mediate cancer immune evasion. MPDL3280A is a human mAb containing an engineered Fc-domain designed to optimize efficacy and safety that
Protection against oxygen toxicity by intravenous injection of liposome-entrapped catalase and superoxide dismutase.
Authors: J F Turrens, J D Crapo, B A Freeman
Journal: Journal of Clinical Investigation (1984)

Survival of rats exposed to 100% oxygen was increased from 69.5 +/- 1.5 to 118.1 +/- 9.9 h (mean +/- SEM, P less than 0.05) when liposomes containing catalase and superoxide dismutase were injected intravenously before and during exposure. The increased survival time in 100% oxygen was also associated with significantly less fluid in the pleural cavity. Rats injected with catalase- and superoxide dismutase-containing liposomes, which had increased survival in 100% oxygen, had increased lung wet weight upon autopsy compared with saline-injected controls (2.9 +/- 0.2 g/lung vs. 4.8 +/- 0.4 g/lung, mean +/- SE, P less than 0.05). Intravenous injection of control liposomes along with catalase and superoxide dismutase in the suspending buffer decreased the mean pleural effusion volume 89% and had no significant effect on survival time. Lung catalase and superoxide dismutase activities were increased 3.1- and 1.7-fold, respectively, 2 h after a single intravenous injection of liposomes containing catalase or superoxide dismutase. Superoxide dismutase activity was also significantly greater than controls in both air- and 100% oxygen-exposed rat lungs, when enzyme activity was assayed 24 h after cessation of injection of control and oxygen-exposed rats with enzyme-containing liposomes every 12 h for 36 h. Free superoxide dismutase and catalase injected intravenously in the absence of liposomes did not increase corresponding lung enzyme activities, affect pleural effusion volume, lung wet weight, or extend the mean survival time of rats exposed to 100% oxygen. The clearance of liposome-augmented 125I-labeled catalase from lung and plasma obeyed first order kinetics according to a one-compartment model. When clearance of liposome-augmented catalase activity or radioactivity were the parameters used for pharmacokinetic studies, the half-life of augmented lung catalase was 1.9 and 2.6 h, respectively. The half-life of liposome-entrapped catalase and superoxide dismutase activity in the circulation was 2.5 and 4 h, respectively, while intravenously injected catalase and superoxide dismutase had a circulation half-life of 23 and 6 min, respectively.
Accelerated blood clearance of PEGylated liposomes following preceding liposome injection: Effects of lipid dose and PEG surface-density and chain length of the first-dose liposomes
Authors: Tatsuhiro Ishida, Masae Harada, Xin Yu Wang, Masako Ichihara, Kenji Irimura, Hiroshi Kiwada
Journal: Journal of Controlled Release (2005)