tbuckley/cabot-search huggingface dataset:
Ointment is evenly spread on the skin, in contrast to creams and solutions
Authors: U.I. Ivens, B. Steinkjer, J. Serup, V. Tetens
Journal: British Journal of Dermatology (2001)

The efficacy of topical therapy depends on the patient spreading the topical drug in an even layer to give a standard dose. Ointments are believed to be more effective than creams and solutions.To compare the application and spreading of four different pharmaceutical vehicles.Twenty-nine healthy volunteers applied a fixed amount (0.1 g) of solution (S), ointment (O), cream (C) and low-viscosity cream (LVC) to the abdominal skin. Area of spread, skin surface lipids (dependent on formulation) and changes in skin surface temperature (cooling due to evaporation of formulation water/alcohol) were measured.Area of spread: O = C = LVC = S. Skin surface lipids: O > C > LVC > S. Difference in skin surface lipids between centre and periphery: O < C = LVC = S. Cooling: O < C = LVC < S.The four formulations were spread to similar areas. The ointment was spread evenly in the treated area while the other formulations were unevenly spread, with a lower dose in the periphery. Creams and solutions have disadvantages as vehicles, as rapid evaporation of formulation water/alcohol, measured as cooling, influences spread, resulting in an uneven topical dose within the treated area. In contrast, ointment is evenly spread and is thus a more appropriate formulation. Patients should be instructed to apply creams and solutions to multiple sites and to spread them quickly.
Origins and Evolution of the Formin Multigene Family That Is Involved in the Formation of Actin Filaments
Authors: D. Chalkia, N. Nikolaidis, W. Makalowski, J. Klein, M. Nei
Journal: Molecular Biology and Evolution (2008)

In eukaryotes, the assembly and elongation of unbranched actin filaments is controlled by formins, which are long, multidomain proteins. These proteins are important for dynamic cellular processes such as determination of cell shape, cell division, and cellular interaction. Yet, no comprehensive study has been done about the origins and evolution of this gene family. We therefore performed extensive phylogenetic and motif analyses of the formin genes by examining 597 prokaryotic and 53 eukaryotic genomes. Additionally, we used three-dimensional protein structure data in an effort to uncover distantly related sequences. Our results suggest that the formin homology 2 (FH2) domain, which promotes the formation of actin filaments, is a eukaryotic innovation and apparently originated only once in eukaryotic evolution. Despite the high degree of FH2 domain sequence divergence, the FH2 domains of most eukaryotic formins are predicted to assume the same fold and thus have similar functions. The formin genes have experienced multiple taxon-specific duplications and followed the birth-and-death model of evolution. Additionally, the formin genes experienced taxon-specific genomic rearrangements that led to the acquisition of unrelated protein domains. The evolutionary diversification of formin genes apparently increased the number of formin's interacting molecules and consequently contributed to the development of a complex and precise actin assembly mechanism. The diversity of formin types is probably related to the range of actin-based cellular processes that different cells or organisms require. Our results indicate the importance of gene duplication and domain acquisition in the evolution of the eukaryotic cell and offer insights into how a complex system, such as the cytoskeleton, evolved.
Antibiotic treatment and risk of gastric cancer
Authors: K Fall
Journal: Gut (2006)

<b>Background/aims:</b><i>Helicobacter pylori</i> infection is undoubtedly an important risk factor for gastric cancer. It remains unclear however whether antibiotic treatment may prevent gastric cancer development. Our aim was to assess long term gastric cancer risks in historic cohorts of patients presumed to have been heavily exposed to antibiotics. <b>Subjects:</b> Using the Swedish Inpatient Register, we identified 501 757 individuals discharged with any one of 10 selected infectious disease diagnoses between 1970 and 2003. <b>Methods:</b> We counted person time and non-cardia gastric cancer occurrences through linkage to virtually complete population and health care registers. Standardised incidence ratios (SIRs) were calculated for comparisons with cancer incidence rates of the general population in Sweden. <b>Results:</b> No reduction in gastric cancer risk was observed in the infectious disease cohort in total (SIR 1.08 (95% confidence intervals 1.00–1.17) or for any of the presumed antibiotic regimens. There were no clear trends towards decreasing risk with time of follow up, but the risk tended to fall with increasing age at first hospitalisation for the infection (p&lt;0.04). <b>Conclusions:</b> Our results do not confirm earlier observational findings of a reduced risk of gastric cancer following exposure to heavy antibiotic treatment among hip replacement patients. Suboptimal drug regimens, inadequate timing of <i>H pylori</i> eradication, or insufficient follow up time may possibly explain the lack of association in this setting. Although our findings do not rule out the cancer preventive potential of <i>H pylori</i> eradication, they emphasise that detection of such an effect, if any, may require considerable efforts.
Hepatocellular Carcinoma in Children and Adolescents: Results From the Pediatric Oncology Group and the Children’s Cancer Group Intergroup Study
Authors: Howard M. Katzenstein, Mark D. Krailo, Marcio H. Malogolowkin, Jorge A. Ortega, Wen Liu-Mares, Edwin C. Douglass, James H. Feusner, Marleta Reynolds, John J. Quinn, Kurt Newman, Milton J. Finegold, Joel E. Haas, Martha G. Sensel, Robert P. Castleberry, Laura C. Bowman
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To determine surgical resectability, event-free survival (EFS), and toxicity in children with hepatocellular carcinoma (HCC) randomized to treatment with either cisplatin (CDDP), vincristine, and fluorouracil (regimen A) or CDDP and continuous-infusion doxorubicin (regimen B). PATIENTS AND METHODS: Forty-six patients were enrolled onto Pediatric Intergroup Hepatoma Protocol INT-0098 (Pediatric Oncology Group (POG) 8945/Children’s Cancer Group (CCG) 8881). After initial surgery or biopsy, children with stage I (n = 8), stage III (n = 25), and stage IV (n = 13) HCC were randomly assigned to receive regimen A (n = 20) or regimen B (n = 26). RESULTS: For the entire cohort, the 5-year EFS estimate was 19% (SD = 6%). Patients with stage I, III, and IV had 5-year EFS estimates of 88% (SD = 12%), 8% (SD = 5%), and 0%, respectively. Five-year EFS estimates were 20% (SD = 9%) and 19% (SD = 8%) for patients on regimens A and B, respectively (P = .78), with a relative risk of 1.2 (95% confidence interval, 0.60 to 2.3) for regimen B when compared with regimen A. Outcome was similar for either regimen within disease stages. Events occurred before postinduction surgery I in 18 (47%) of 38 patients with stage III or IV disease, and tumor resection was possible in two (10%) of the remaining 20 children with advanced-stage disease after chemotherapy. CONCLUSION: Children with initially resectable HCC have a good prognosis and may benefit from the use of adjuvant chemotherapy. Outcome was uniformly poor for children with advanced-stage disease treated with either regimen. New therapeutic strategies are needed for the treatment of advanced-stage pediatric HCC.
PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients
Authors: F. Perrone, A. Lampis, M. Orsenigo, M. Di Bartolomeo, A. Gevorgyan, M. Losa, M. Frattini, C. Riva, S. Andreola, E. Bajetta, L. Bertario, E. Leo, M.A. Pierotti, S. Pilotti
Journal: Annals of Oncology (2008)
Folic Acid, Xanthine Oxidase, and Uric Acid
Authors: BERNARD PLOUVIER
Journal: Annals of Internal Medicine (1978)

Letters and Corrections1 February 1978Folic Acid, Xanthine Oxidase, and Uric AcidBERNARD PLOUVIER, M.D., BERNARD DEVULDER, M.D.BERNARD PLOUVIER, M.D.Search for more papers by this author, BERNARD DEVULDER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-88-2-269_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: With reference to the letter of K. A. Oster (1), we wish to report a trial of treatment with folic acid, at daily dose of 1 mg/kg body weight during 1 month, in 10 patients with gout (five with hyperuricemia and hyperuricosuria, five with isolated hyperuricosuria).In one case, an attack of gout developed on the sixth day. Blood uric acid has been determined weekly in the patients with hyperuricemia, and no change was found during the period of folic acid administration. We observed a fall of 10% in urine uric acid excretion during the first week...Reference1. OSTER K: Folic acid and xanthine oxidase. Ann Intern Med 86:367, 1977 LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: BERNARD PLOUVIER, M.D.; BERNARD DEVULDER, M.D.Affiliations: Service de Médecine Générale et Néphrologie B, Hopital Calmette Centre Hospitalo—Universitaire 59037 Lille Cedex France PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byGoutGoutInhibition of buttermilk xanthine oxidase by folate analogues and derivatives 1 February 1978Volume 88, Issue 2Page: 269-269KeywordsBloodBody weightExcretionFallsFolic acidGoutUric acidUrine ePublished: 1 December 2008 Issue Published: 1 February 1978 PDF downloadLoading ...
The presence of dominant T-cell clones in peripheral blood of patients with collagen vascular disorders: a prospective study of 97 cases
Authors: O. Dereure, B. Gubler, D. Bessis, B. Guillot, J-J. Guilhou, J. Clot, J-F. Eliaou
Journal: British Journal of Dermatology (2005)

T-lymphocyte dysfunction has been seldom investigated in collagen vascular disorders. The search for dominant T-cell clones has been scarcely reported, although the presence of such clones might be expected in disorders showing immune responses directed against a variety of autoantigens.We conducted a systematic search for dominant T-cell clones in peripheral blood in patients with collagen vascular disorders. Patients and methods Ninety-seven patients with collagen vascular disorders were studied (7 cutaneous and 38 systemic lupus erythematosus; 8 multiple morphea; 12 regional scleroderma; 32 systemic sclerosis of the CREST type). A dominant T-cell clone was searched for in peripheral blood by polymerase chain reaction targeting the T-cell receptor gamma chain followed by a size analysis of amplified fragments. Peripheral blood from patients with nonlymphocyte-dependent disorders and matched by age and sex was assessed in the same conditions. Results in both groups were compared using nonparametric statistical tests.Overall, a circulating dominant T-cell clone was found in 52% of patients compared with 16.9% in controls. More precisely, such a dominant clone was present in 43% and 37% of cutaneous and systemic lupus erythematosus, respectively, in 75% of multiple morphea, 75% of regional scleroderma and 60% of CREST syndrome patients. The percentages in all subsets of patients were significantly higher than in the control group.The presence of a dominant T-cell clone in peripheral blood is significantly more frequent in collagen vascular disorders than in controls, especially in patients with scleroderma, whatever the clinical subset, which suggests T-cell involvement in the immune response dysfunction in these diseases classically characterized by disturbances of B lymphocytes. The relevance of such a dominant clone regarding diagnosis, pathomechanisms, long-term outcome and visceral prognosis of these diseases as well as therapeutic decisions remains to be evaluated.
Transmural variation in autoregulation of right ventricular blood flow.
Authors: S Yonekura, N Watanabe, H F Downey
Journal: Circulation Research (1988)

We examined transmurally the right coronary autoregulatory flow response to varied perfusion pressures in 11 anesthetized, open-chest dogs. Right coronary artery flow was measured electromagnetically, and its transmural distribution was defined with 15-micron radioactive microspheres. Heart rate, mean aortic blood pressure, right ventricular systolic pressure, end-diastolic pressure, and dP/dtmax were constant. At 100 mm Hg, subepicardial flow averaged 0.48 +/- 0.04 ml/min/g, and subendocardial flow averaged 0.56 +/- 0.05 ml/min/g. In contrast to the left coronary circulation, right coronary hypotension did not cause preferential subendocardial ischemia. As right coronary perfusion pressure was decreased from 100 to 40 mm Hg in five dogs, subepicardial and subendocardial flows were reduced similarly by 35-36%. As right coronary perfusion pressure was elevated from 100 to 150 mm Hg in six dogs, right ventricular subepicardial blood flow increased by 31%, whereas subendocardial blood flow increased by 70%. Right ventricular subendocardial-to-subepicardial flow ratios averaged 1.15-1.20 for perfusion pressures of 40 to 120 mm Hg, and they increased to 1.36 +/- 0.05 at 150 mm Hg. Right coronary artery autoregulatory closed-loop gain averaged 0.47 +/- 0.06 between 70 and 100 mm Hg and was greater than zero from 40 to 120 mm Hg. Between 120 and 150 mm Hg, gain fell to -0.15 +/- 0.10. Regional gain varied from 0.59 +/- 0.10 to 0.44 +/- 0.08 in subepicardium as pressure was decreased from 100 to 40 mm Hg. Subendocardial gains were similar to subepicardial gains over this pressure range.(ABSTRACT TRUNCATED AT 250 WORDS)
Isolation and Molecular Profiling of Bone Marrow Micrometastases Identifies <i>TWIST1</i> as a Marker of Early Tumor Relapse in Breast Cancer Patients
Authors: Mark A. Watson, Lourdes R. Ylagan, Kathryn M. Trinkaus, William E. Gillanders, Michael J. Naughton, Katherine N. Weilbaecher, Timothy P. Fleming, Rebecca L. Aft
Journal: Clinical Cancer Research (2007)

Micrometastatic cells detected in the bone marrow have prognostic significance in breast cancer. These cells are heterogeneous and likely do not exhibit uniform biological behavior. To understand the molecular diversity of disseminated cancer cells that reside in bone marrow, we enriched this cell population and did global gene expression profiling in the context of a prospective clinical trial involving women with clinical stage II/III breast cancer undergoing neoadjuvant chemotherapy.Enrichment of TACSTD1 (EpCAM)-expressing cells from bone marrow of breast cancer patients was achieved using immunomagnetic beads. Gene expression profiles were compared between enriched cell populations and whole bone marrow from 5 normal volunteers and 23 breast cancer patients after neoadjuvant chemotherapy treatment. Enriched cells from bone marrow samples of breast cancer patients before treatment or at 1 year follow-up were also analyzed (total of 87 data sets). The expression of transcripts specifically detected in enriched cell populations from breast cancer patients was correlated with 1-year clinical outcome using quantitative reverse transcription-PCR in an independent cohort of bone marrow samples.Analysis of EpCAM-enriched bone marrow cells revealed specific expression of a subgroup of transcripts, including the metastasis regulator, TWIST1. Most transcripts identified, including TWIST1, were not expressed in enriched populations of bone marrow from normal volunteers, suggesting that this expression profile reflects a signature of breast cancer bone marrow micrometastases that persist after chemotherapy. In an independent set of bone marrow samples obtained before any treatment, TWIST1 expression correlated with early disease relapse.Disseminated breast cancer cells present in bone marrow after chemotherapy possess unique transcriptional signatures. Genes whose expression is overrepresented in these cell populations, such as TWIST1, may prove to be excellent markers of early distant relapse in breast cancer patients.
P439Comparative metabolomics identifies conserved metabolic pathways that control mitochondrial ROS production during ischaemia reperfusion injury
Authors: E Chouchani, V Pell, E Gaude, D Aksentijevic, M Shattock, S Davidson, M Duchen, C Frezza, T Krieg, M Murphy
Journal: Cardiovascular Research (2014)

Ischaemia-reperfusion (IR) injury, which occurs when blood supply to an organ is disrupted and then restored, underlies many disorders, notably heart attack and stroke. Thus while reperfusion of ischaemic tissue is essential for survival, it also initiates oxidative damage, cell death, and aberrant immune responses, driven in large part by generation of mitochondrial reactive oxygen species (ROS). Although mitochondrial ROS production in IR is established, it has generally been considered a non-specific response to reperfusion, consistent with the many apparently unconnected interventions that decrease IR damage. In contrast to this view, we have identified a critical post-translational modification on mitochondrial complex I that is sufficient to abolish mitochondrial ROS during IR. Using MitoSNO - a novel selective inhibitor of complex I - we establish that S-nitrosation of a single cysteine residue on the ND3 subunit sufficient to impair oxidoreductase activity on in the target protein.This inhibitory modification in turn diminished both ROS and tissue necrosis at reperfusion.

These findings led us to pursue the intriguing hypothesis that mitochondrial ROS production during IR could be controlled by a distinct metabolic process that interacts with mitochondrial complex I. We developed a comparative in vivo metabolomic analysis and unexpectedly identified conserved metabolic pathways responsible for controlling mitochondrial ROS production during IR. In doing so, we establish a universal metabolic signature of ischaemic injury in a range of tissues that are predictive for mitochondrial ROS production through mitochondrial complex I during reperfusion of ischaemic tissue. Pharmacological inhibition of these pathways is sufficient to ameliorate in vivo IR injury in murine models of heart attack, stroke and kidney damage. Thus our work identifies a general metabolic response of tissues to ischaemia and reperfusion that provides a unifying explanation for many hitherto unconnected aspects of IR injury.
The Prognostic Significance of “Switching” in Patients With Bipolar Disorder: A 10-Year Prospective Follow-Up Study
Authors: Mario Maj, Raffaele Pirozzi, Lorenza Magliano, Luca Bartoli
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: This study explored whether "switching" (i.e., the direct transition from one mood polarity to the other) has significant prognostic implications in patients with bipolar disorder. METHOD: Bipolar disorder patients (N=97) whose first prospectively observed episode included at least one mood polarity switch and 97 bipolar disorder patients whose index episode was monophasic were compared with respect to several demographic and historical variables, symptomatic features of the index episode, time to recovery from the index episode, time spent in an affective episode during a prospective observation period, and psychopathological and psychosocial outcome at a 10-year follow-up interview. RESULTS: Patients whose index episode included at least two mood polarity switches spent significantly more time in an affective episode during the observation period and had a significantly worse psychopathological and psychosocial outcome 10 years after recruitment than those whose index episode included only one mood polarity switch or was monophasic. Patients whose polyphasic index episode started with depression spent a significantly higher proportion of time in an affective episode and had a significantly worse 10-year outcome than those whose polyphasic index episode started with mania or hypomania. Retention of the switching pattern throughout the observation period was seen in 42.4% of patients whose index episode started with mania and in 65.2% of those whose index episode started with depression. CONCLUSIONS: An index episode including at least two mood polarity switches, especially if starting with depression, is associated with a poor long-term outcome in patients with bipolar disorder. This pattern represents a significant target for new pharmacological and psychosocial treatment strategies.
Phospholipase A2-induced cytoprotection of proximal tubules
Authors: R A Zager, K M Burkhart, D S Conrad, D J Gmur, M Iwata
Journal: Journal of the American Society of Nephrology (1996)

Addition of phospholipase A2 (PLA2) to isolated proximal tubular segments (PTS) has previously been shown to decrease hypoxic cell death without altering ATP concentrations. The study presented here was undertaken to identify determinant(s) of this protection, and to define the spectrum of injuries against which it can operate. PTS were extracted from mouse kidneys and subjected to diverse forms of injury (hypoxia/reoxygenation, antimycin A, Ca2+ ionophore, amphotericin B, FeSO4, and myohemoglobin). In subtoxic doses, addition of PLA2 significantly reduced hypoxic- and antimycin A-induced injury (percentage of lactate dehydrogenase release); however, a dose-dependent exacerbation of all other forms of injury resulted. The ability of PLA2 to mitigate hypoxic injury remained intact despite the inhibition of Na,K-ATPase (ouabain) or the inducement of cytoskeletal disruption (cytochalasin D). However, it was negated by minimally toxic amphotericin B or Ca2+ ionophore doses, indicating its dependence on preserved ionic gradients. Nevertheless, neither lowering/removing buffer Ca2+ or NaCl concentrations, nor hypertonic mannitol addition reproduced the cytoprotective effect of PLA2. PLA2 induced synergistic deacylation in hypoxic tubules, suggesting that unsaturated fatty-acid accumulation might mediate its cytoprotective effect. The fact that the addition of exogenous arachidonate, but not palmitate, to tubules protected against hypoxia, but worsened nonhypoxic forms of injury, supported this hypothesis. Since arachidonate might induce "feedback" inhibition of intracellular PLA2, the ability of an intracellular phospholipase inhibitor (ONO-RS-082; Biomol, Plymouth, PA) to blunt hypoxic damage was tested. This agent fully reproduced the cytoprotective effect of PLA2. It was concluded that: (1) PLA2-induced cytoprotection is relatively specific for ATP depletion injury; (2) it is dependent on, but not explained by, maintenance of NaCl and Ca2+ gradients; (3) it does not require Na,K-ATPase activity or cytoskeletal integrity for its expression; and (4) extracellular PLA2, via arachidonate release, may cause feedback inhibition of intracellular PLA2, thereby protecting critical intracellular targets from attack.