tbuckley/cabot-search huggingface dataset:
Sgk1 Gene Expression in Kidney and Its Regulation by Aldosterone
Authors: Jianghui Hou, Helen J. L. Speirs, Jonathan R. Seckl, Roger W. Brown
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. The serine-threonine kinase sgk1 was recently identified as a gene rapidly induced by mineralocorticoids, resulting in increased sodium transport in vitro . To carefully localize and quantify the renal sgk1 expression response to aldosterone, in situ hybridization was performed on kidneys of mice having aldosterone excess over a range of doses and durations. In control and adrenalectomized animals, the glomeruli and inner medullary collecting ducts were the major sites of sgk1 expression, which was maintained independent of aldosterone. Sgk1 upregulation induced by aldosterone excess exhibited spatio-temporal heterogeneity. Both acute (3-h) and chronic (6-d) aldosterone excess stimulated sgk1 expression in the distal nephron, i.e. , from the distal convoluted tubules through to the outer medullary collecting ducts. Treatments for 6 d with low sodium diet (0.03% [I]) and aldosterone infusions (50 μg/kg per d [II], 150 μg/kg per d [III], and 750 μg/kg per d [IV]) generated elevation of circulating aldosterone. Across these treatments (I through IV), the circulating level correlated with the progressive induction of sgk1 expression, with highly stimulated tubules first appearing in cortex (I) and continuing downward (II) until there was a strong stimulation throughout outer medulla (III and IV). Interestingly, chronic but not acute aldosterone excess caused a slight increase of sgk1 expression in glomerulus (30 to 50%; P &lt; 0.01) and a dramatic downregulation in the initial portion of inner medulla, which could result from diminished interstitial osmolarity. Relative quantification ( versus control) of sgk1 upregulation in individual tubules revealed: ( 1 ) a 1.8-fold increase of sgk1 mRNA at 3 h (150 μg/kg injection) and ( 2 ) a dose-dependence of chronic upregulation reaching a ceiling of eightfold elevation.
Prevalence of Insulin Resistance Syndrome in Southwestern France and Its Relationship With Inflammatory and Hemostatic Markers
Authors: Pedro Marques-Vidal, Elizabeth Mazoyer, Vanina Bongard, Pierre Gourdy, Jean-Bernard Ruidavets, Ludovic Drouet, Jean Ferrières
Journal: Diabetes Care (2002)

To assess the prevalence and relationships of insulin resistance syndrome (IRS) with inflammatory and hemostatic markers in a representative sample of the population of Southwestern France aged 35-64 years.In this cross-sectional study, data were collected from 597 men and 556 women and were assessed regarding BMI, blood pressure, total and HDL cholesterol levels, triglyceride level, glucose level, plasma insulin level, white blood cell count, fibrinogen level, factor VII level, von Willebrand factor, C-reactive protein level, soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule-1, and soluble CD(14). Insulin resistance was defined by homeostasis model assessment > or =3.8.Prevalence of IRS was higher in men than in women (23 vs. 12%, respectively; P < 0.001) and increased with age in both sexes (9, 24, and 34% for age groups 35-44, 45-54, and 55-64 years, respectively, for men and 4, 10, and 21% for women). After adjusting for age, alcohol consumption, tobacco smoking, and also for menopause in women, subjects (men and women) with IRS had significantly higher white blood cell count, factor VII levels, coagulating factor VII levels, and C-reactive protein levels than the other subjects. In men, further increases in soluble intercellular adhesion molecule and soluble vascular cell adhesion molecule-1 were noted, whereas in women, the differences were borderline significant. Conversely, no differences were found in fibrinogen, von Willebrand factor, and soluble CD(14) in both sexes.IRS is relatively common in residents of Southwestern France and is related to a deleterious increase in hemostatic and inflammatory parameters.
Non-invasive versus invasive respiratory support in preterm infants at birth: systematic review and meta-analysis
Authors: G. M. Schmolzer, M. Kumar, G. Pichler, K. Aziz, M. O'Reilly, P.-Y. Cheung
Journal: BMJ (2013)

<b>Objective</b> To assess the role of nasal continuous positive airway pressure (CPAP) initiated at birth for prevention of death and bronchopulmonary dysplasia in very preterm infants. <b>Design</b> Systematic review. <b>Data sources</b> PubMed, Embase, the Cochrane Central Register of Controlled Trials, and online Pediatric Academic Society abstracts from the year of inception to June 2013. <b>Eligibility criteria for selecting studies</b> Randomised controlled trials evaluating the effect of nasal CPAP compared with intubation in preterm infants born at less than 32 weeks’ gestation and presenting the outcomes of either death or bronchopulmonary dysplasia, or both (defined as the need for oxygen support or mechanical ventilation at 36 weeks corrected gestation), during hospital stay. <b>Results</b> Four randomised controlled trials (2782 participants) met the inclusion criteria, with 1296 infants in the nasal CPAP group and 1486 in the intubation group. All the trials reported bronchopulmonary dysplasia independently at 36 weeks corrected gestation, with borderline significance in favour of the nasal CPAP group (relative risk 0.91, 95% confidence interval 0.82 to 1.01, risk difference −0.03, 95% confidence interval −0.07 to 0.01). No difference in death was observed (relative risk 0.88, 0.68 to 1.14, risk difference −0.02, −0.04 to 0.01, respectively). Pooled analysis showed a significant benefit for the combined outcome of death or bronchopulmonary dysplasia, or both, at 36 weeks corrected gestation for babies treated with nasal CPAP (relative risk 0.91, 0.84 to 0.99, risk difference −0.04, -0.07 to 0.00), number needed to treat of 25). <b>Conclusion</b> One additional infant could survive to 36 weeks without bronchopulmonary dysplasia for every 25 babies treated with nasal CPAP in the delivery room rather than being intubated.
Plasmepsins as potential targets for new antimalarial therapy
Authors: Karolina Ersmark, Bertil Samuelsson, Anders Hallberg
Journal: Medicinal Research Reviews (2006)

Malaria is one of the major diseases in the world. Due to the rapid spread of parasite resistance to available antimalarial drugs there is an urgent need for new antimalarials with novel mechanisms of action. Several promising targets for drug intervention have been revealed in recent years. This review addresses the parasitic aspartic proteases termed plasmepsins (Plms) that are involved in the hemoglobin catabolism that occurs during the erythrocytic stage of the malarial parasite life cycle. Four Plasmodium species are responsible for human malaria; P. vivax, P. ovale, P. malariae, and P. falciparum. This review focuses on inhibitors of the haemoglobin-degrading plasmepsins of the most lethal species, P. falciparum; Plm I, Plm II, Plm IV, and histo-aspartic protease (HAP). Previously, Plm II has attracted the most attention. With the identification and characterization of new plasmepsins and the results from recent plasmepsin knockout studies, it now seems clear that in order to achieve high-antiparasitic activities in P. falciparum-infected erythrocytes it is necessary to inhibit several of the haemoglobin-degrading plasmepsins. Herein we summarize the structure–activity relationships of the Plm I, II, IV, and HAP inhibitors. These inhibitors represent all classes which, to the best of our knowledge, have been disclosed in journal articles to date. The 3D structures of inhibitor/plasmepsin II complexes available in the protein data bank are briefly discussed and compared. © 2006 Wiley Periodicals, Inc. Med Res Rev, 26, No. 5, 626–666, 2006
Heterogeneity in the Prognostic Significance of 12p Deletion and Chromosome 5 Amplification in Multiple Myeloma
Authors: William Tapper, Laura Chiecchio, Gian Paolo Dagrada, Zoe J. Konn, David M. Stockley, Alex J. Szubert, Walter M. Gregory, Susan E. Bell, Graham H. Jackson, J. Anthony Child, Gareth J. Morgan, Fiona M. Ross
Journal: Journal of Clinical Oncology (2010)

The International Myeloma Working Group (IMWG) recently evaluated fluorescent in situ hybridization (FISH) testing in multiple myeloma and concluded that there was only sufficient evidence to recommend routine testing for three markers, t(4; 14), t(14;16), and 17p13 deletion. 1However, the authors suggested that new markers detected by array methods may also have prognostic value when sufficient evidence has been accrued.A recent article in Journal of Clinical Oncology 2 addressed exactly this question and concluded that two new markers in combination with serum ␤ 2microglobulin (S␤ 2 M) gave a more powerful prognostic index than the IMWG markers.Using a molecular karyotyping method to identify copy-number abnormalities in 192 patients newly diagnosed with multiple myeloma, the authors identified two regions associated with a poor prognosis, deletion of 12p13.31 [del(12p13.31)]and amplification of 1q23. 3 [amp(1q23.3)],and one region associated with a good prognosis, amplification of 5q31. 3 [amp(5q31.3)].Multivariate survival analysis identified del(12p13.31),amp(5q31.3),and S␤ 2 M levels as independent prognostic factors, whereas amp(1q23.3)lost its significance.The prognostic significance of del(12p13.31)and amp(5q31.3)with S␤ 2 M was confirmed in an independent cohort of 273 patients with multiple myeloma who were tested using interphase-FISH.We aimed to replicate these findings in a cohort of patients newly diagnosed with multiple myeloma who were enrolled onto the Medical Research Council (MRC) Myeloma IX trial. 3This trial was structured with two different arms depending on the age and fitness of patients, and only the younger, fitter patients were given high-dose therapy.To match the cohort examined by Avet-Loiseau et al 2 as closely as possible, we selected for this analysis only patients who were 66 years of age or younger and who were treated with high-dose therapy [ranging from n ϭ 547 for t(4;14) to n ϭ 256 for del(12p13.3);
Involvement of the Paxillin Pathway in JB6 Cl41 Cell Transformation
Authors: Yasuaki Tatsumi, Yong-Yeon Cho, Zhiwei He, Hideya Mizuno, Hong Seok Choi, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2006)

Paxillin is a substrate of the Src tyrosine onco-kinase and is involved in cell transformation, cell spreading, migration, and cancer development mediated through the mitogen-activated protein kinase signaling cascades. Here, we showed that paxillin plays a key role in skin cell transformation induced by epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA). To investigate the mechanism of paxillin's role in cell transformation, we established a paxillin knockdown stably transfected cell line by introducing small interfering RNA-paxillin (si-paxillin). The si-paxillin cells displayed a dramatic suppression of cell proliferation and anchorage-independent cell transformation induced by EGF or TPA compared with si-mock control cells. In si-paxillin cells, decreased activator protein-1 (AP-1)-dependent luciferase activity corresponded with suppressed AP-1 DNA binding activity. Importantly, knockdown of paxillin inhibited EGF- or TPA-induced c-Jun phosphorylation at Ser(63) and Ser(73). Furthermore, total c-Jun protein level was dramatically decreased in si-paxillin cells and was dependent on serum deprivation time. The down-regulation of c-Jun was restored in si-paxillin cells by treatment with the proteasome inhibitor lactacystin but not by the lysosome inhibitor leupeptin. These results clearly provided evidence that paxillin regulates c-Jun protein level and plays a key role in cell transformation most likely through the regulation of c-Jun stability.
Hepcidin in anemia of chronic heart failure
Authors: Vijay Divakaran, Sachin Mehta, David Yao, Saamir Hassan, Steven Simpson, Erwin Wiegerinck, Dorine W. Swinkels, Douglas L. Mann, Vahid Afshar‐Kharghan
Journal: American Journal of Hematology (2010)

Anemia is a common finding among patients with chronic heart failure (HF). Although comorbidities, such as kidney failure, might contribute to the pathogenesis of anemia, many patients with HF do not have any other obvious etiology for their anemia. We investigated whether anemia in HF is associated with an elevation in hepcidin concentration. We used time-of-flight mass spectrometry to measure hepcidin concentration in urine and serum samples of patients with HF and in control subjects. We found that the concentration of hepcidin was lower in urine samples of patients with HF compared with those of control subjects. Serum hepcidin was also reduced in HF but was not significantly lower than that in controls. There were no significant differences between hepcidin levels in patients with HF and anemia compared with patients with HF and normal hemoglobin level. We concluded that hepcidin probably does not play a major role in pathogenesis of anemia in patients with chronic HF.
Identification of Leishmania at the species level with matrix-assisted laser desorption ionization time-of-flight mass spectrometry
Authors: C. Cassagne, F. Pratlong, F. Jeddi, R. Benikhlef, K. Aoun, A.-C. Normand, F. Faraut, P. Bastien, R. Piarroux
Journal: Clinical Microbiology and Infection (2013)
Phase II Trial of Gefitinib 250 mg Daily in Patients with Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck
Authors: Ezra E.W. Cohen, Madeleine A. Kane, Marcy A. List, Bruce E. Brockstein, Bhoomi Mehrotra, Dezheng Huo, Ann M. Mauer, Carolyn Pierce, Allison Dekker, Everett E. Vokes
Journal: Clinical Cancer Research (2005)

Abstract Purpose: An objective response rate of 11% was reported in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) treated with 500 mg daily gefitinib although the recommended dose in lung cancer is 250 mg. This study evaluated the efficacy and toxicity of 250 mg daily gefitinib in patients with recurrent and/or metastatic SCCHN. Experimental Design: Phase II trial with objective response rate as the primary end point. Measurements of quality of life and levels of serum vascular endothelial growth factor and transforming growth factor-α were assessed before and during therapy. Results: In 70 patients, 1 (1.4%) partial response was observed. Median progression-free survival and overall survival were 1.8 and 5.5 months, respectively. Quality of life scores improved transiently during the first weeks of therapy before returning to baseline. Median vascular endothelial growth factor and transforming growth factor-α levels were above the normal range but were not predictive of outcome. Four patients experienced grade 3 drug-related adverse events. Rash of any grade was observed in 64% of subjects. Correlation between disease control (partial response + stable disease), progression-free survival, and overall survival and grade of cutaneous toxicity was observed (P = 0.001, 0.001, and 0.008 respectively). Conclusions: Gefitinib monotherapy at 250 mg in recurrent and/or metastatic SCCHN seems to have less activity than was previously observed for 500 mg daily. A dose-response relationship may exist for this agent in SCCHN and grade of cutaneous toxicity attributable to gefitinib is a clinical predictor of better outcome.
Effectiveness and Risks of Contraception
Authors: W Droegemueller, R Bressler
Journal: Annual Review of Medicine (1980)

At this time the ideal contraceptive, i.e., the safe, simple, inexpensive, totally effective, easily reversible contraceptive without side effects and not used at the time of the sexual act, has yet to be developed. This review highlights recent improvements in standard contraceptives and the views of these physicians concerning current risk benefit ratios. The benefits of tubal ligation are obvious, for few procedures offer more relief from anxiety and have such a high chance of success. Failure rates with tubal ligation range from 1 in 200 to 1 in 1000 cases, depending on the type of operation performed. Advances in laparoscopic technique, including the use of either silastic bands or spring loaded clips, have virtually eliminated the inadvertent "burns" associated with electrocautery. Due to the fact that clips and bands produce less tissue damage, it is anticipated that there will be a higher potential for reversibility. Recent literature has emphasized a specific syndrome that develops subsequent to tubal ligation; its major components are dysfunctional uterine bleeding and pelvic pain. The true incidence of this syndrome is difficult to establish but is estimated to be 10-33% in women who have had laparoscopic tubal fulguration. Vasectomy is simpler with less immediate morbidity, less expense, and easier reversibility than tubal ligation. The failure rate is slightly less with male sterilization. The most alarming recent report in relation to vasectomy is that it may be a surgical model for autoimmune disease. The theoretical effectiveness of steriodal contraceptives is 1 pregnancy/1000 woman years of use, and the actual use effectiveness is 5-8 pregnancies/1000 woman years of use. Many review articles document the various adverse effects that have been recorded in the literature. The mortality risk from oral contraceptive (OC) use in women under age 35 is 3 in 100,000. Few authors comment on the beneficial effects of OCs. These include fewer menstrual disorders, inhibition of the development of benign breast disease and a decrease in the incidence of functional ovarian cysts, and a decrease in some medical illnesses including peptic ulcers and rheumatoid arthritis. Liver adenomas are the most prominent complication of OCs that have been related to chronic use. The IUD has several benefits including a failure or pregnancy rate of 2-3/100 woman years of use. OCs are 3 times more dangerous than the IUD in regard to mortality, but the incidence of hospitalizations is 5-10 times higher with the IUD than with OCs. As effectiveness of barrier methods depends on high motivation, in studies of all forms of vaginal contraception and condoms there is a wide discrepancy between theoretical and use effectiveness. The lowest mortality rates are associated with barrier contraceptives with a back-up of early abortion when the method fails.
THE EFFECT OF ETHYL URETHANE ANESTHESIA ON THE ACID-BASE EQUILIBRIUM AND CELL CONTENTS OF THE BLOOD
Authors: James A. Hawkins, James B. Murphy
Journal: The Journal of Experimental Medicine (1925)

When anesthesia is produced in rabbits or rats by injections of ethyl urethane, the C02 content and pH of the whole blood of the animal are more or less rapidly increased to a point where there is a marked uncompensated alkalosis which reaches its maximum at 24 hours and persists for 48 hours. The increase in the C02 content and pH of the whole blood is accompanied by a decrease in the circulating lymphocytes and an increase in the polymorphonuclear leucocytes.
Prognostic Stratification of Patients With Vasospastic Angina
Authors: Yusuke Takagi, Jun Takahashi, Satoshi Yasuda, Satoshi Miyata, Ryusuke Tsunoda, Yasuhiro Ogata, Atsushi Seki, Tetsuya Sumiyoshi, Motoyuki Matsui, Toshikazu Goto, Yasuhiko Tanabe, Shozo Sueda, Toshiaki Sato, Satoshi Ogawa, Norifumi Kubo, Shin-ichi Momomura, Hisao Ogawa, Hiroaki Shimokawa
Journal: Journal of the American College of Cardiology (2013)
Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor Differentially Modulate Early Postnatal Coronary Angiogenesis
Authors: Robert J. Tomanek, Alexander Sandra, Wei Zheng, Tommy Brock, Robert J. Bjercke, Jennifer S. Holifield
Journal: Circulation Research (2001)

Abstract —The roles of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF [FGF-2]) in early postnatal regulation of coronary angiogenesis were investigated by administering neutralizing antibodies to these growth factors between postnatal days 5 and 12. Immunohistochemistry and Western blotting both revealed decreases in VEGF protein in the hearts of rats treated with either antibody. In contrast, bFGF mRNA increased in both treated groups, whereas VEGF mRNA was unchanged. Using stereological assessment of perfusion-fixed hearts, we found that both anti-VEGF and anti-bFGF inhibited the rapid and marked capillary growth that occurs during this time period and that the effects of the two neutralizing antibodies are not additive. Arteriolar growth, as indicated by a lower length density, was inhibited by anti-bFGF, but not anti-VEGF. When both anti-VEGF and anti-bFGF were administered, arteriolar length density was not significantly lower, but the population of small arterioles (&lt;15 μm) was markedly reduced, whereas the percentage of large arterioles (26 to 50 μm) more than doubled. Thus, inhibition of both growth factors negated or limited the formation of small arterioles and facilitated an expansion of the largest arterioles. These in vivo data are the first to document that during the early neonatal period, (1) both VEGF and bFGF modulate capillary growth, (2) bFGF facilitates arteriolar growth, and (3) the two growth factors interact to establish the normal hierarchy of the arteriolar tree.
Re: Wu et al.: Outdoor Activity during Class Recess Reduces Myopia Onset and Progression in School Children (Ophthalmology 2013;120:1080-1085)
Authors: Virgilio Galvis, Alejandro Tello, Yuly A. Castellanos, Paul A. Camacho, Angélica M. Prada, Carlos M. Rangel
Journal: Ophthalmology (2013)
Allergen-induced Increases in Bone Marrow T Lymphocytes and Interleukin-5 Expression in Subjects with Asthma
Authors: Lorna J. Wood, Roma Sehmi, Sandra Dorman, Qutayba Hamid, Meri K. Tulic, Richard M. Watson, Ronan Foley, Parveen Wasi, Judah A. Denburg, Gail Gauvreau, Paul M. O'Byrne
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Inhaled allergen challenge of subjects with atopic asthmatic increases bone marrow eosinophil progenitor cells. Interleukin-5 (IL-5) specifically induces growth and maturation of eosinophils. This study examined the effect of allergen challenge on the number of bone marrow total and CD3+ cells expressing IL-5 protein and IL-5 mRNA in subjects with asthma who developed either allergen-induced isolated early responses, or early and late asthmatic responses (dual responders). At 24 hours after allergen challenge, dual responders had significantly greater blood and airway eosinophilia compared with early responders. There were significant increases in the percentage of bone marrow CD3+ cells (p < 0.005) in both groups. However, there were significant differences in the increases in bone marrow IL-5 mRNA+ (p < 0.005), CD3+ (p < 0.005), and IL-5 mRNA+ CD3+ (p < 0.005) cells between the dual and early responder groups. These results suggest that, in subjects with atopic asthma, inhaled allergen causes trafficking of T lymphocytes to the bone marrow, and that in subjects who develop late responses and greater blood and airway eosinophilia after inhalation of allergen, there is a significant increase in the ability of bone marrow cells, particularly T lymphocytes, to produce IL-5.
Antigen-specific targeting and elimination of EBV-transformed B cells by allergen toxins
Authors: Michael Stöcker, Torsten Klockenbring, Michael Huhn, Thomas Nachreiner, Daniel Wicklein, Arnd Petersen, Ralf Bauer, Roland Goerlich, Rainer Fischer, Stefan Barth
Journal: Journal of Allergy and Clinical Immunology (2005)