tbuckley/cabot-search huggingface dataset:
Hepatitis C virus infection in a community in the Nile Delta: Risk factors for seropositivity
Authors: Mostafa Habib, Mostafa K. Mohamed, Fatma Abdel‐Aziz, Laurence S. Magder, Mohamed Abdel‐Hamid, Foda Gamil, Salah Madkour, Nabiel N. Mikhail, Wagida Anwar, G. Thomas Strickland, Alan D. Fix, Ismail Sallam
Journal: Hepatology (2001)

The purpose of this study was to identify risk factors for hepatitis C virus (HCV) infection in a rural village in the Nile Delta with a high prevalence of antibodies to HCV (anti–HCV). One half of the village households were systematically selected, tested for anti–HCV, and interviewed: 973 of 3,999 (24.3%) subjects were anti–HCV–positive (reflecting prior HCV infection but not necessarily current liver disease), with nearly equal prevalence among males and females. Anti–HCV prevalence increased sharply with age among both males and females, from 9.3% in those 20 years of age and younger to &gt;50% in those older than 35, suggesting a cohort effect with reduced transmission in recent years. Multivariate regression was used to estimate independent effects of risk factors on seropositivity. Among those over 20 years of age, the following risk factors were significantly associated with seropositivity: age ( P &lt; .001); male gender (odds ratio [OR] = 2.5, 95% CI = 1.3–4.7); marriage (OR = 4.1, 2.4–6.9); anti–schistosomiasis injection treatment (OR = 2.0, 1.3–2.9); blood transfusion (OR = 1.8, 1.1–2.9), invasive medical procedure (surgery, catheterization, endoscopy, and/or dialysis) (OR = 1.5, 1.1–1.9); receipt of injections from “informal” health care provider (OR = 1.3, 1.0–1.6); and cesarean section or abortion (OR = 1.4, 1.0–1.9). Exposures not significantly related to anti–HCV positivity in adults included: history of, or active infection with, Schistosoma mansoni , sutures or abscess drainage, goza smoking in a group, and shaving by community barbers. Among those 20 years old or younger, no risk factors were clearly associated with anti–HCV positivity; however, circumcision for boys by informal health care providers was marginally associated with anti–HCV (OR = 1.7, 1.0–3.0). Prevention programs focused primarily on culturally influenced risks in rural Egyptian communities are being implemented and evaluated.
Parasite-induced Lipoxin A4 Is an Endogenous Regulator of IL-12 Production and Immunopathology in <i>Toxoplasma gondii</i> Infection
Authors: Julio Aliberti, Charles Serhan, Alan Sher
Journal: The Journal of Experimental Medicine (2002)

The production of interleukin (IL)-12 is critical for the development of interferon (IFN)-γ–dependent resistance to Toxoplasma gondii. Nevertheless, when this response is dysregulated, such as occurs in the absence of IL-10, the uncontrolled inflammation that results can have lethal consequences for the host. Recently, we demonstrated that lipoxin (LX)A4, an eicosanoid mediator that depends on 5-lipoxygenase (LO) for its biosynthesis, exerts a regulatory role on dendritic cell IL-12 production triggered artificially by a T. gondii extract. We now formally establish the physiological relevance of this pathway in the systemic control of IL-12 production induced by live T. gondii infection and demonstrate its function to be distinct from that of IL-10. Thus, T. gondii–exposed wild-type, but not 5-LO–deficient animals, produced high levels of serum LXA4 beginning at the onset of chronic infection. Moreover, 5-LO−/−, in contrast to wild-type mice, succumbed during the same period displaying a marked encephalitis. The increased mortality of the 5-LO−/− animals was also associated with significant elevations of IL-12 and IFN-γ and was completely prevented by the administration of a stable LXA4 analogue. Together, these findings demonstrate a new pathway involving the induction of host LXs for the in vivo regulation of proinflammatory responses during microbial infection.
Early magnesium modifications as a surrogate marker of efficacy of cetuximab-based anticancer treatment in KRAS wild-type advanced colorectal cancer patients
Authors: B. Vincenzi, S. Galluzzo, D. Santini, L. Rocci, F. Loupakis, P. Correale, R. Addeo, A. Zoccoli, A. Napolitano, F. Graziano, A. Ruzzo, A. Falcone, G. Francini, G. Dicuonzo, G. Tonini
Journal: Annals of Oncology (2010)
Genetic disorders in the Arab world
Authors: Lihadh Al-Gazali, Hanan Hamamy, Shaikha Al-Arrayad
Journal: BMJ (2006)

Available evidence suggests that congenital and genetic disorders are responsible for a major proportion of infant mortality, morbidity, and handicap in Arab countries.1–3 The population of the region is characterised by large family size, high maternal and paternal age, and a high level of inbreeding with consanguinity rates in the range of 25-60%.1 2 4 w1 Certain disorders are common throughout the Arab world, including haemoglobinopathies, glucose-6-phosphate dehydrogenase deficiency, different congenital malformations caused by recessive genes, and several metabolic disorders.1 2 Other recessive disorders cluster in certain groups and subpopulations.1 2 5 Genetic services vary in extent and coverage in different Arab countries, but mostly they remain patchy, selective, and inadequate.2 5 6 We present the magnitude of the problem and the currently available genetic services in Arab countries, together with recommendations for developing strategies for prevention. In view of the good coverage of primary healthcare systems in most Arab countries, community genetic services that include screening programmes could be strengthened by the efficient training of primary healthcare personnel.2 Available data suggest that genetic and congenital disorders are more common in Arab countries than in industrialised countries; recessively inherited disorders account for a substantial proportion of physical and mental handicap.1–3 6 Several factors may contribute to the high prevalence of genetically determined disorders:
Steroid sulphatase deficiency in patients initially diagnosed as ichthyosis vulgaris or recessive X-linked ichthyosis
Authors: T. YOSHIIKE, T. MATSUI, H. OGAWA
Journal: British Journal of Dermatology (1985)

Twenty-one patients with ichthyosis were classified as either ichthyosis vulgaris (IV) (five cases) or recessive X-linked ichthyosis (RXLI) (sixteen cases) by using a steroid sulphatase assay of plantar callus and peripheral leukocytes. The patients had presented with various clinical manifestations, which had resulted in some initial misdiagnoses. Cases which initially resemble IV may in fact be RXLI, although we found that if a case is initially diagnosed as RXLI it is unlikely to be a case of IV.
MDM2 overexpression is associated with short survival in adults with medulloblastoma
Authors: Maria Teresa Giordana, Debora Duó, Sabrina Gasverde, Elisa Trevisan, Andrea Boghi, Isabella Morra, Luca Pradotto, Alessandro Mauro, Adriano Chió
Journal: Neuro-Oncology (2002)

In adult medulloblastoma, postoperative radiotherapy is significantly effective in prolonging time to recurrence and survival time; however, the response of individual cases to radiotherapy, that is the total survival, is different. Apoptosis is an important cellular response to radiation. It can be hypothesized that the individual radiosensitivity of medulloblastomas depends on the individual capability to undergo apoptosis. p53 protein is involved in the apoptotic response to ionizing radiation; loss of function of p53 can be the consequence not only of TP53 mutations, but also of amplification and/or overexpression of the MDM2 gene. We have analyzed cerebellar medulloblastomas from 51 adults (>16 years of age) for MDM2 gene amplification (by differential polymerase chain reaction assay), TP53 gene mutation (by polymerase chain reaction single-strand conformation polymorphism analysis of exons 5-8), and immunohistochemical expression of p53 (clone DO1) and MDM2 (clone IF2). The results have been evaluated in relation to age, tumor location, classic or desmoplastic type, MIB-1 labeling index, and total survival. No tumor had MDM2 amplification. Ten tumors had MDM2-positive tumor cells. One case had a mutated TP53 gene; 16/51 cases had intense p53 immunostaining. Only 2 MDM2 protein-positive tumors were also p53-positive. Both subgroups of MDM2- and p53-positive tumors had a significantly shorter postoperative survival. In conclusion, the overexpression of MDM2 protein and the accumulation of wild-type p53 are unrelated in adult medulloblastoma; they may result in a reduced apoptotic response after radiotherapy and contribute to a shortened survival. Also, MDM2 amplification and TP53 gene mutation are rare events in medulloblastomas of adults.
Stereological and functional analysis of liver mitochondria from rats with secondary biliary cirrhosis: Impaired mitochondrial metabolism and increased mitochondrial content per hepatocyte
Authors: Stefan Krähenbühl, Sonja Krähenbühl-Glauser, Jörg Stucki, Peter Gehr, Jürg Reichen
Journal: Hepatology (1992)

Mitochondrial and cytosolic functions were studied in vivo and in perfused livers from rats with secondary biliary cirrhosis induced by bile duct ligation for 5 wk and in sham–operated controls. The livers were stereo–logically analyzed, and mitochondrial and cytosolic functions were related to liver structure. Oxygen consumption by perfused livers expressed per stereo–logically determined mitochondrial volume was decreased by 49% in bile duct—ligated rats compared with control rats. Glucose production (expressed per mitochondrial volume) was reduced by more than 90% in bile duct ligation, whereas urea production was not affected. Lactate production, a cytosolic function, was increased fivefold in bile duct ligation, and both the lactate/pyruvate and the β–hydroxybutyrate/acetoacetate ratios were increased in the liver perfusate of bile duct—ligated rats. In comparison with control rats, the stereologically determined mitochondrial volume fraction per hepatocyte was increased by 28% in bile duct—ligated rats. Activities of mitochondrial enzymes expressed per area of mitochondrial membrane or per mitochondrial volume were either unchanged (ATPase, cytochrome c oxidase and glutamate dehydrogenase) or decreased (monoamine oxidase) in bile duct ligation. Thus in comparison with control rats, mitochondrial metabolism is impaired in perfused livers from bile duct—ligated rats; increased mitochondrial volume per hepatocyte may represent a strategy to maintain hepatic energy metabolism in rats with secondary biliary cirrhosis. (Hepatology 1992;15:1167–1172).
Binding of Retinoids to Human Breast Cancer Cell Lines and their Effects on Cell Growth
Authors: Andre Lacroix, Marc E. Lippman
Journal: Journal of Clinical Investigation (1980)

Vitamin A and its analogues (retinoids) regulate the differentiation of epithelial tissues. Retinoids inhibit the induction of rat mammary cancers by carcinogens in vivo, and cellular binding proteins for retinoids have been demonstrated in some human breast cancer samples. In this study, we examined the model system of human breast cancer cell lines in long-term tissue culture for effects of retinoids on growth and for the presence of cellular retinoid binding proteins. Retinoic acid and retinol inhibit the growth of of MCF-7, Hs578T, and ZR-75-B cell lines. Retinoic acid is more potent than retinol in this regard: 50% growth inhibition is achieved by 6 nM retinoic acid in ZR-75-B and by 700 nM in MCF-7 and Hs578T, whereas 5-8 muM retinol is required in all three cell lines. The time to onset of growth inhibition varies markedly between cell lines and is not related to cell density or doubling time. Retinoic acid increases the doubling time of MCF-7 and ZR-75-B by two- to threefold, but causes cell death in Hs578T. The growth inhibition is reversible in every cell line by removal of retinoic acid. Specific and distinct binding of [(3)H]retinoic acid and [(3)H]retinol is present in cytosols of MCF-7 and Hs578T cells as assessed by sucrose density gradient centrifugation. In ZR-75-B, [(3)H]retinoic acid binding was present, but no binding of [(3)H]retinol was detectable. This study reveals that retinoids may play an important role in the regulation and treatment of human breast cancer and that human breast cancer cell lines represent a useful model to study this role.
Controlled Exposure Study of Air Pollution and T-Wave Alternans in Volunteers without Cardiovascular Disease
Authors: Marjan Kusha, Stephane Masse, Talha Farid, Bruce Urch, Frances Silverman, Robert D Brook, Diane R Gold, Iqwal Mangat, Mary Speck, Krishnakumar Nair, Kwaku Poku, Chris Meyer, Murray A Mittleman, Gregory A Wellenius, Kumaraswamy Nanthakumar
Journal: Environmental Health Perspectives (2012)

Epidemiological studies have assessed T-wave alternans (TWA) as a possible mechanism of cardiac arrhythmias related to air pollution in high-risk subjects and have reported associations with increased TWA magnitude. In this controlled human exposure study, we assessed the impact of exposure to concentrated ambient particulate matter (CAP) and ozone (O3) on T-wave alternans in resting volunteers without preexisting cardiovascular disease. Seventeen participants without preexisting cardiovascular disease were randomized to filtered air (FA), CAP (150 μg/m3), O3 (120 ppb), or combined CAP + O3 exposures for 2 hr. Continuous electrocardiograms (ECGs) were recorded at rest and T-wave alternans (TWA) was computed by modified moving average analysis with QRS alignment for the artifact-free intervals of 20 beats along the V2 and V5 leads. Exposure-induced changes in the highest TWA magnitude (TWAMax) were estimated for the first and last 5 min of each exposure (TWAMax_Early and TWAMax_Late respectively). ΔTWAMax (Late-Early) were compared among exposure groups using analysis of variance. Mean ± SD values for ΔTWAMax were -2.1 ± 0.4, -2.7 ± 1.1, -1.9 ± 1.5, and -1.2 ± 1.5 in FA, CAP, O3, and CAP + O3 exposure groups, respectively. No significant differences were observed between pollutant exposures and FA. In our study of 17 volunteers who had no preexisting cardiovascular disease, we did not observe significant changes in T-wave alternans after 2-hr exposures to CAP, O3, or combined CAP + O3. This finding, however, does not preclude the possibility of pollution-related effects on TWA at elevated heart rates, such as during exercise, or the possibility of delayed responses.
Mechanism of galanin's inhibitory action on pancreatic enzyme secretion: modulation of cholinergic transmission--studies in vivo and in vitro.
Authors: K H Herzig, G Brunke, I Schon, M Schaffer, U R Folsch
Journal: Gut (1993)

This study examined the inhibitory mechanism of galanin, a 29 amino acid polypeptide on pancreatic enzyme secretion in anaesthetised rats, isolated pancreatic acini, and lobules. Urethane anaesthetised rats with pancreatic fistulas pretreated with 3-0-methyl-glucopyranose (500 mg/kg/h) were stimulated with an intravenous bolus of 2-deoxyglucose (2-DG) (75 mg/kg). Maximal amylase secretion was mean (SEM) 274 (19)% of basal secretion. Atropine (150 micrograms/kg/h) and galanin (10 nmol/kg/h) almost completely inhibited 2-DG stimulated amylase secretion suggesting an inhibition of cholinergic transmission. To further test this possibility this study investigated the effect of galanin on carbachol and cholecystokinin stimulated amylase release from isolated pancreatic acini. Galanin did not suppress carbachol or cholecystokinin stimulated amylase release, indicating that galanin inhibits exocrine secretion by indirect mechanisms. The cholinergic pathway was assessed by using pancreatic lobules containing intrapancreatic neurons. Veratridine, a sodium channel activator, dose dependently stimulated amylase release. Veratridine (100 microM) stimulated amylase release by 411 (10)% of basal secretion. Atropine (1 microM) or tetrodotoxin (1 microM) almost completely blocked veratridine stimulated amylase release. Galanin (1 microM) significantly inhibited veratridine stimulated amylase release with a maximal inhibition of 50% (p &lt; 0.05). In addition, when lobules were incubated with [3H]-choline, galanin significantly (p &lt; 0.05) inhibited veratridine stimulated release of newly synthesised [3H]-acetylcholine. Thus galanin inhibits pancreatic secretion by inhibiting cholinergic transmission. These studies show that galanin inhibits rat pancreatic enzyme secretion by an indirect mechanism by reducing cholinergic transmission.
TM-06 * MYC AND MYCN DISRUPTION OF THE MOLECULAR CLOCK IN CANCER CELLS
Authors: A. Hsieh, B. Altman, Z. Stine, A. Gouw, A. Venkataraman, B. Li, P. Goraksha-Hicks, S. Diskin, D. Bellovin, M. Celeste Simon, J. Rathmell, M. Lazar, J. Maris, D. Felsher, J. Hogenesch, C. Dang
Journal: Neuro-Oncology (2014)

Cancer cells are known to have a metabolic advantage, but it is not known whether the circadian clock, which couples metabolic and cell cycles, restrains cancer cell metabolism and growth. We report that the deregulated expression of the MYC or MYCN oncogene disrupts the molecular clock by inducing NR1D1 (Rev-erbα) to diminish expression and dampen oscillation of ARNTL (Bmal1) that could be rescued by knockdown of Rev-erb. The expression of Rev-erbα is highly correlated with MYC expression in human B cell lymphoma, human T-cell acute lymphoblastic leukemia, murine hepatocellular carcinoma cells and human neuroblastoma cells. MYC or MYCN directly upregulates Rev-erbα expression by binding to its promoter. Suppression of Rev-erbα diminished hepatocellular cancer cell growth, illustrating Rev-erbα's role in MYC-induced tumorigenesis. Furthermore, Rev-erbα expression is a predictor of poor clinical outcome for human neuroblastoma and correlates with MYCN expression. Our results demonstrate an unsuspected link between oncogenic transformation and circadian arrhythmia, which may be metabolically advantageous for cancer cells. Having observed that Myc and N-Myc disrupt circadian rhythm in tumor cells, suggesting a therapeutic opportunity could exist in the window between circadian regulation of the ebb-and-flow of normal cell metabolism and the sustained, not oscillate non-circadian cancer metabolism. The understanding of these basic mechanisms from our work should lead to better cancer treatment strategies that reduce side effects and increase effectiveness.
A Mouse with a Loss-of-function Mutation in the c-Cbl TKB Domain Shows Perturbed Thymocyte Signaling without Enhancing the Activity of the ZAP-70 Tyrosine Kinase
Authors: Christine B.F. Thien, Robin M. Scaife, John M. Papadimitriou, Maria A. Murphy, David D.L. Bowtell, Wallace Y. Langdon
Journal: The Journal of Experimental Medicine (2003)

The unique tyrosine kinase binding (TKB) domain of Cbl targets phosphorylated tyrosines on activated protein tyrosine kinases (PTKs); this targeting is considered essential for Cbl proteins to negatively regulate PTKs. Here, a loss-of-function mutation (G304E) in the c-Cbl TKB domain, first identified in Caenorhabditis elegans, was introduced into a mouse and its effects in thymocytes and T cells were studied. In marked contrast to the c-Cbl knockout mouse, we found no evidence of enhanced activity of the ZAP-70 PTK in thymocytes from the TKB domain mutant mouse. This finding contradicts the accepted mechanism of c-Cbl–mediated negative regulation, which requires TKB domain targeting of phosphotyrosine 292 in ZAP-70. However, the TKB domain mutant mouse does show aspects of enhanced signaling that parallel those of the c-Cbl knockout mouse, but these involve the constitutive activation of Rac and not enhanced PTK activity. Furthermore, the enhanced signaling in CD4+CD8+ double positive thymocytes appears to be compensated by the selective down-regulation of CD3 on mature thymocytes and peripheral T cells from both strains of mutant c-Cbl mice.
Who will benefit from tracheostomy ventilation in motor neuron disease?
Authors: J. M. Shneerson
Journal: Thorax (2011)

high-concentration oxygen therapy causes a clinically significant increase in PtCO 2 and they recommended the use of a titrated oxygen regime in the treatment of severe asthma.These results mirror those of a similar study performed recently in patients with COPD. 9 In this randomised, controlled, prehospital study, participants allocated to titrated oxygen therapy were significantly less likely to have respiratory acidosis (mean difference in pH 0.12; SE 0.05; p¼0.01; n¼38) or hypercapnoea (mean difference in PaCO 2 À33.6 mm Hg; SE 16.3; p¼0.02; n¼39) than patients receiving high-concentration oxygen.Treatment with titrated oxygen was also associated with a 58% reduction in mortality, the primary outcome in this study.As asthma and COPD are prevalent diseases in the Western world, and acute exacerbations of either are associated with an increased risk of death, it is beholden to health professionals to ensure that they do not contribute to this outcome.We now have strong evidence to support the BTS guidelines on emergency oxygen use, which recommend that it be approached in the same way as any other drug, recognising that adverse outcomes may eventuate from either inappropriately low or high concentrations.Should the guidelines be revised in the light of this new evidence to better align recommendations with the philosophy of keeping arterial oxygen saturations 'within the target saturation range' that aim to 'achieve normal or near-normal oxygen saturation' and move away from any suggestion that high-concentration oxygen should be administered in the absence of objective evidence of a physiological need?With the advent of lowcost portable oxygen saturation monitors, surely it is time we followed the guideline exhortations to measure the fifth vital sign, as in the words of Willy Wonka 'it's the only way if you want it just right'.
BOOP presenting with haemoptysis and multiple cavitary nodules
Authors: M Froudarakis, D Bouros, R Loire, K Valasiadou, D Tsiftsis, NM Siafakas
Journal: European Respiratory Journal (1995)

A 47 year old woman developed idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) presenting with haemoptysis and diffuse multiple cavitary nodules. The disease was histologically confirmed by open lung biopsy after other entities had been excluded. The patient responded to a course of corticosteroids. This BOOP should be added to the list of diseases with multiple cavitary nodules.
CHLOKPKOMAZINE DERMATITIS IN NURSES.
Authors: R. H. SEVILLE
Journal: British Journal of Dermatology (1956)

Journal Article CHLOKPKOMAZINE DERMATITIS IN NURSES. Get access R. H. SEVILLE, M.D., M.R.C.P. R. H. SEVILLE, M.D., M.R.C.P. Dermatologist, Royal Infirmary and Beaumont Hospital, Lancaster Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 68, Issue 10, 1 October 1956, Pages 332–335, https://doi.org/10.1111/j.1365-2133.1956.tb12758.x Published: 01 October 1956