tbuckley/cabot-search huggingface dataset:
Effect of Vitamin D Status on the Equilibrium between Occupied and Unoccupied 1,25-Dihydroxyvitamin D Intestinal Receptors in the Chick
Authors: Willi Hunziker, Marian R. Walters, June E. Bishop, Anthony W. Norman
Journal: Journal of Clinical Investigation (1982)

The dynamic equilibrium between in vivo occupied and unoccupied 1,25-dihydroxyvitamin D3[1,25(OH)2D3] receptors of the chick intestinal mucosa was investigated by the exchange assay previously reported [(1980). J. Biol. Chem.255: 9534-9537]. These parameters and their correlation to biological response, i.e., the levels of intestinal vitamin D-dependent calcium binding protein (CaBP), were assessed under different physiological conditions. After a single 1,25(OH)2D3 injection (3.25 nmol), occupied receptor levels increased sharply to a maximum between 1 and 2 h, followed by a rapid decline. A single dose of 1α-hydroxy-vitamin D3 [1α(OH)D3], an analog that requires 25-hydroxylation for biological activity, resulted in a protracted, albeit lower, response with maximal receptor occupancy at 6 h and half maximal levels 24 h after injection. The intestinal receptor occupancy patterns mirrored the serum 1,25(OH)2D3 levels after either 1,25(OH)2D3 or 1α(OH)D3 treatment. Additionally, time-course (half-life) of blood disappearance of 1,25(OH)2D3 and occupied receptor levels were similar (1.9 and 2.3 h, respectively), suggesting that the amount of occupied 1,25(OH)2D3 receptor is determined by a simple equilibrium between serum 1,25(OH)2D3 and unoccupied receptors. A dose-response study after intramuscular 1,25(OH)2D3 injection yielded a hyperbolic curve with an apparent plateau at 70% receptor occupancy, corresponding to 5 nmol 1,25(OH)2D3 injected. Half-maximal occupancy was reached after a dose of 1 nmol 1,25(OH)2D3, corresponding to 1.5 ng 1,25(OH)2D3/ml serum. From this value the apparent Kd in vivo is 3.7 nM, which is similar to that determined in vitro. A 10-fold increase in the 1α(OH)D3 dose resulted in less than a doubling of the levels of serum 1,25(OH)2D3, occupied 1,25(OH)2D3 receptors, or CaBP. Under all experimental conditions, there was a positive correlation between occupied receptor and CaBP levels; however, the slope of the lines depended on the times chosen for the assays due in part to the lag period for CaBP induction and its accumulation within the cell. Conversely, the correlation between serum 1,25-(OH)2D3 levels and occupied receptor levels yielded a single regression line independent of the observation time. Short and long-term treatment with different vitamin D metabolites, estrogen, progesterone, or cortisol did not affect the levels of total intestinal 1,25(OH)2D3 receptor. Under normal physiological conditions, only 10-15% of the total 1,25(OH)2D3 receptor population was occupied by ligand. These studies provide a basis for further investigations of physiological and biochemical parameters of the vitamin D endocrine system and their clinical applications.
PATHOGEN-SELECTIVE CULTURES AS AN AID TO THE DIAGNOSIS OF INFECTIVE FOCI
Authors: E. C. Lowe
Journal: BMJ (1928)

8 JTULYJ 2!, It9281 PATOG3B *sitE-ClVE OltJiSURES -AS}AW AID TO DAGNOSIS.[rMEDICAL JOURNA el)idemic, further inivestigations in this direction were hampered.The 7 remiiaining serunms, though positive for the Flexner group, were equivocal as to type by ordinary agglutination miiethods, an-d the amiiounts of the serumis did not permit of absorptioni tests.'In four instances bacilli shlowing the morphological and cultural clharacteristics of the dysentery group, but not agglutinating with any of the stock antiseluiims except the platients', were isolated.One of these organiismiis was also well agglutinated by anotlher patient's serumii.Nonie of tlle serums in this epidemic agglutinated Shiga cultur es, anid
Measles, rubella, and congenital rubella syndrome - United States and Mexico, 1997-1999.
Authors: E. Ferreira, V. Carrión, C. A. Lucas, P. Kuri, A. Flisser, J. L. D. Ortega, J. I. S. Preciado, R. T. Conyer
Journal: MMWR Morbidity and Mortality Weekly Report (2000)
THE VASELINE TUBE AND SYRINGE METHOD OF MICRO GAS ANALYSIS OF BACTERIAL CULTURES
Authors: J. Howard Brown
Journal: The Journal of Experimental Medicine (1922)

There has been described the use of the vaseline tube and the tuberculin syringe for the study of gas production by bacteria. A comparison is made of some of the results obtained by the use of the method here described, the Smith fermentation tube, and the tube of Eldredge and Rogers. The reports of CO2 production by certain streptococci by Ayers, Rupp, and Mudge and by Bacterium typhosus by Nichols have been confirmed by the author's method. The data presented serve to illustrate the accuracy and technical possibilities of the method. In addition to economy of glassware, medium, and labor, the vaseline tube and syringe method of micro gas analysis possesses the following advantages. (1) Gas produced above either liquid or solid media may be measured and analyzed. (2) The gas produced may be measured in terms of a definite and constant quantity of medium used. (3) The vaseline tube provides a closed system from which gases do not escape into the air. (4) Separate determinations of the CO2 produced in and above fluid media may be made. (5) Determinations may be made from very small samples of material. (6) Numerous gas analyses of the same culture may be made at various times during the growth of the culture without contaminating or destroying it. (7) Gas production may be observed under both anaerobic and controlled aerobic conditions.
Multiple Oncogenic Changes (<i>K-RASV12</i>, p53 Knockdown,<i>Mutant EGFRs, p16</i>Bypass, Telomerase) Are Not Sufficient to Confer a Full Malignant Phenotype on Human Bronchial Epithelial Cells
Authors: Mitsuo Sato, Melville B. Vaughan, Luc Girard, Michael Peyton, Woochang Lee, David S. Shames, Ruben D. Ramirez, Noriaki Sunaga, Adi F. Gazdar, Jerry W. Shay, John D. Minna
Journal: Cancer Research (2006)

Abstract We evaluated the contribution of three genetic alterations (p53 knockdown, K-RASV12, and mutant EGFR) to lung tumorigenesis using human bronchial epithelial cells (HBEC) immortalized with telomerase and Cdk4-mediated p16 bypass. RNA interference p53 knockdown or oncogenic K-RASV12 resulted in enhanced anchorage-independent growth and increased saturation density of HBECs. The combination of p53 knockdown and K-RASV12 further enhanced the tumorigenic phenotype with increased growth in soft agar and an invasive phenotype in three-dimensional organotypic cultures but failed to cause HBECs to form tumors in nude mice. Growth of HBECs was highly dependent on epidermal growth factor (EGF) and completely inhibited by EGF receptor (EGFR) tyrosine kinase inhibitors, which induced G1 arrest. Introduction of EGFR mutations E746-A750 del and L858R progressed HBECs toward malignancy as measured by soft agar growth, including EGF-independent growth, but failed to induce tumor formation. Mutant EGFRs were associated with higher levels of phospho-Akt, phospho–signal transducers and activators of transcription 3 [but not phospho-extracellular signal-regulated kinase (ERK) 1/2], and increased expression of DUSP6/MKP-3 phosphatase (an inhibitor of phospho-ERK1/2). These results indicate that (a) the HBEC model system is a powerful new approach to assess the contribution of individual and combinations of genetic alterations to lung cancer pathogenesis; (b) a combination of four genetic alterations, including human telomerase reverse transcriptase overexpression, bypass of p16/RB and p53 pathways, and mutant K-RASV12 or mutant EGFR, is still not sufficient for HBECs to completely transform to cancer; and (c) EGFR tyrosine kinase inhibitors inhibit the growth of preneoplastic HBEC cells, suggesting their potential for chemoprevention. (Cancer Res 2006; 66(4): 2116-28)
HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis
Authors: Nelson Sewankambo, Ronald H Gray, Maria J Wawer, Lynn Paxton, Denise McNairn, Fred Wabwire-Mangen, David Serwadda, Chuanjun Li, Noah Kiwanuka, Sharon L Hillier, Lorna Rabe, Charlotte A Gaydos, Thomas C Quinn, Joseph Konde-Lule
Journal: The Lancet (1997)

BackgroundIn-vitro research has suggested that bacterial vaginosis may increase the survival of HIV-1 in the genital tract. Therefore, we investigated the association of HIV-1 infection with vaginal flora abnormalities, including bacterial vaginosis and depletion of lactobacilli, after adjustment for sexual activity and the presence of other sexually transmitted diseases (STDs).MethodsDuring the initial survey round of our community-based trial of STD control for HIV-1 prevention in rural Rakai District, southwestern Uganda, we selected 4718 women aged 15–59 years. They provided interview information, blood for HIV-1 and syphilis serology, urine for detection of Chlamydia trachomatis and Neisseria gonorrhoeae, and two self-administered vaginal swabs for culture of Trichomonas vaginalis and gram-stain detection of vaginal flora, classified by standardised, quantitative, morphological scoring. Scores 0–3 were normal vaginal flora (predominant lactobacilli). Higher scores suggested replacement of lactobacilli by gram-negative, anaerobic microorganisms (4–6 intermediate; 7–8 and 9–10 moderate and severe bacterial vaginosis).FindingsHIV-1 frequency was 14·2% among women with normal vaginal flora and 26·7% among those with severe bacterial vaginosis (p<0·0001). We found an association between bacterial vaginosis and increased HIV-1 infection among younger women, but not among women older than 40 years; the association could not be explained by differences in sexual activity or concurrent infection with other STDs. The frequency of bacterial vaginosis was similar among HIV-1-infected women with symptoms (55·0%) and without symptoms (55·7%). The adjusted odds ratio of HIV-1 infection associated with any vaginal flora abnormality (scores 4–10) was 1·52 (95% Cl 1·22–1·90), for moderate bacterial vagniosis (scores 7–8) it was 1·50 (1·18–1·89), and for severe bacterial vaginosis (scores 9–10) it was 2·08 (1·48–2·94).InterpretationThis cross-sectional study cannot show whether disturbed vaginal flora increases susceptibility to HIV-1 infection. Nevertheless, the increased frequency of HIV-1 associated with abnormal flora among younger women, for whom HIV-1 acquisition is likely to be recent, but not among older women, in whom HIV-1 is likely to have been acquired earlier, suggests that loss of lactobacilli or presence of bacterial vaginosis may increase susceptibility to HIV-1 acquisition. If this inference is correct, control of bacterial vaginosis could reduce HIV-1 transmission.
Pergolide Is an Inhibitor of Voltage-Gated Potassium Channels, Including Kv1.5, and Causes Pulmonary Vasoconstriction
Authors: Zhigang Hong, Andrew J. Smith, Stephen L. Archer, Xi-Chen Wu, Daniel P. Nelson, Douglas Peterson, Gerhard Johnson, E. Kenneth Weir
Journal: Circulation (2005)

Background— Pergolide produces clinical benefit in Parkinson disease by stimulating dopamine D 1 and D 2 receptors. An increased incidence of carcinoid-like heart valve disease (CLHVD) has been noted in pergolide users, reminiscent of that induced by certain anorexigens used for weight reduction. Anorexigens that modulate serotonin release and reuptake, such as dexfenfluramine, were withdrawn from sale because of CLHVD. Interestingly, the anorexigens also caused pulmonary arterial hypertension (PAH). Anorexigens were shown to enhance hypoxic pulmonary vasoconstriction, in part by inhibiting voltage-gated K + channels (Kv) in pulmonary artery smooth muscle cells (PASMCs). Although PAH has not been associated with pergolide use, we hypothesized that pergolide might have similar effects on hypoxic pulmonary vasoconstriction and Kv channels. Methods and Results— Pergolide enhanced hypoxic pulmonary vasoconstriction in the isolated perfused rat lung compared with control lungs (mean pulmonary artery pressure 32±3 versus 21±2 mm Hg; P &lt;0.01). Pergolide also caused vasoconstriction in rat pulmonary artery rings. Pergolide inhibited PASMC potassium current density, resulting in membrane depolarization (from −51±2 to −44±1 mV) and increased cytosolic calcium in both rat and human PASMCs. Pergolide directly inhibited heterologously expressed Kv1.5 and K Ca channels. Conclusions— Pergolide causes Kv channel inhibition and, despite being from a different class of drugs, has pulmonary vascular effects reminiscent of dexfenfluramine. Coupled with their shared proclivity to induce CLHVD, these findings suggest that clinical monitoring for pergolide-induced PAH should be considered.
The Association Between Impaired Glucose Tolerance and Birth Weight Among Black and White Women in Central North Carolina
Authors: Tina M. Saldana, Anna Maria Siega-Riz, Linda S. Adair, David A. Savitz, John M. Thorp
Journal: Diabetes Care (2003)

OBJECTIVE—This study examines the relationship of glucose intolerance during pregnancy to birth weight among black and white participants of the Pregnancy, Infection, and Nutrition Study. RESEARCH DESIGN AND METHODS—This prospective cohort study recruited women from prenatal clinics in central North Carolina at 24–29 weeks’ gestation. A 1-h 50-g glucose challenge test (GCT) and 100-g oral glucose tolerance test (OGTT) were conducted. Impaired glucose tolerance (IGT) was defined as one high value on the OGTT, gestational diabetes mellitus (GDM) as two or more high values, and normal glucose tolerance (NGT) was defined as a low or high value on the GCT screen but no high values on the OGTT. Women with known glucose status and birth outcome information were included in this analysis (n = 2055). RESULTS—Black women with IGT had higher rates of both macrosomia (38.5%) and large for gestational age (LGA) (53.9%) compared with white women (10.0% and 13.2%). Black infants’ birth weights (3,800 g) and prevalence of macrosomia and LGA were significantly higher among mothers with IGT compared with NGT women (birth weight, 3,184 g; macrosomia, 7.0%; LGA, 11.6%). In contrast, among white infants, there was no significant increase in birth weight, macrosomia, or LGA associated with the mother’s glucose tolerance status. In addition, there was no effect of GDM on birth weight in either group. CONCLUSIONS—This study suggests that, independent of maternal prepregnant weight, there may be significant increased risk of macrosomia among black IGT women but not among white IGT women. Further investigations into factors that may contribute to the observed results are needed.
Triple Antithrombotic Therapy in Patients With Atrial Fibrillation and Coronary Artery Stents
Authors: Jeremy S. Paikin, Douglas S. Wright, Mark A. Crowther, Shamir R. Mehta, John W. Eikelboom
Journal: Circulation (2010)

A 76-year-old man with rate-controlled atrial fibrillation (AF), diabetes mellitus, and prior stroke who is receiving warfarin to prevent recurrent stroke presents to the emergency department with chest pain, elevated serum troponin, and an ECG that demonstrates ST depression in the precordial leads.Cardiac catheterization reveals an ulcerated plaque and partially obstructive thrombus in the left circumflex coronary artery.Percutaneous coronary intervention is performed with placement of 2 baremetal stents.What is the optimal antithrombotic therapy?What is the optimal antithrombotic therapy if the patient receives drug-eluting stents instead of bare-metal stents?
Treatment of interdigital-type tinea pedis with a 2-week regimen of wearing hygienic socks loaded with antifungal microcapsules: A randomized, double-blind, placebo-controlled study
Authors: Chun-Wah Marcus Yuen, Joanne Yip, Hing-Cheong Cheung, Li-Wei Liu, Chi-Him Luk, W-Celeste Wai
Journal: Journal of the American Academy of Dermatology (2013)
Colonic Contribution to Uremic Solutes
Authors: Pavel A. Aronov, Frank J.-G. Luo, Natalie S. Plummer, Zhe Quan, Susan Holmes, Thomas H. Hostetter, Timothy W. Meyer
Journal: Journal of the American Society of Nephrology (2011)

Microbes in the colon produce compounds, normally excreted by the kidneys, which are potential uremic toxins. Although p-cresol sulfate and indoxyl sulfate are well studied examples, few other compounds are known. Here, we compared plasma from hemodialysis patients with and without colons to identify and further characterize colon-derived uremic solutes. HPLC confirmed the colonic origin of p-cresol sulfate and indoxyl sulfate, but levels of hippurate, methylamine, and dimethylamine were not significantly lower in patients without colons. High-resolution mass spectrometry detected more than 1000 features in predialysis plasma samples. Hierarchical clustering based on these features clearly separated dialysis patients with and without colons. Compared with patients with colons, we identified more than 30 individual features in patients without colons that were either absent or present in lower concentration. Almost all of these features were more prominent in plasma from dialysis patients than normal subjects, suggesting that they represented uremic solutes. We used a panel of indole and phenyl standards to identify five colon-derived uremic solutes: α-phenylacetyl-l-glutamine, 5-hydroxyindole, indoxyl glucuronide, p-cresol sulfate, and indoxyl sulfate. However, compounds with accurate mass values matching most of the colon-derived solutes could not be found in standard metabolomic databases. These results suggest that colonic microbes may produce an important portion of uremic solutes, most of which remain unidentified.
EFFECTS OF DIETARY NITRATE SUPPLEMENTATION ON 5 KM RUNNING TIME TRIAL PERFORMANCE IN TRAINED FEMALE RUNNERS
Authors: R Lanceley, M Ranchordas, A Ruddock
Journal: British Journal of Sports Medicine (2013)

Ingestion of dietary nitrate supplementation enhances athletic time trial performance but data on its effectiveness in trained female runners is limited. The purpose of this study was to investigate the effect of beetroot juice supplementation (BRJ) on 5 km running time trial performance compared to a placebo (PLA) and no supplementation (CON). Using a double-blind, repeated-measures crossover design with a 14 day washout period, 11 trained female runners (age 20±3 years, 52.6±4.6 mL.kg.min −1 , body mass 53.0±3.9 kg, stature 164.2±5.8 cm) ingested 2×70 mL of either BRJ (∼8 mmoL·d −1 nitrate) or PLA for 4 days and 2.5 h before performing a 5 km time trial. Blood pressure (BP), mean heart rate (HR), post-test blood lactate (BLa), 5 km time trial and 1 km split times were assessed. No main effect was found for change in systolic BP (CON=122±8, PLA=120±7, BRJ=114±9 mm Hg), but trends towards reductions after BRJ were observed, BRJ vs CON -8 mm Hg (-10 to 5; 90% CI, ES=0.82) and BRJ vs PLA 6 mm Hg (9 to 2; 90% CI, ES=0.64). No main effect was found for 5 km time trial performance (CON=1287±126, PLA=1268±109, BRJ=1237±109 s) but trends towards reductions after BRJ were observed, BRJ vs CON −49 s (73 to −26; 90% CI, ES=0.44) and BRJ and PLA −31 s (−48 to −14; 90% CI, ES=0.30). 1 km split times were similar between conditions except for the 2 nd km where BRJ was faster than CON by 16 s (−25 to −7; 90% CI and ES=0.61) and PLA by 12 s (20 to 4; 90% CI and ES=0.57). No between group differences were observed for mean HR (CON=182±8, PLA 181±7, BRJ=182±7 bpm −1 ; or post time trial BLa (CON=6.8±1.9, PLA=6.9±1.9, BRJ=6.9±1.9 mmol . L −1 ). Although not statistically significant, these results suggest BRJ supplementation improved 5 km time trial performance over PLA by 31 s (2.4%). Athletes should consider ingesting BRJ to improve 5 km running performance.
Combining GFR and Albuminuria to Classify CKD Improves Prediction of ESRD
Authors: Stein I. Hallan, Eberhard Ritz, Stian Lydersen, Solfrid Romundstad, Kurt Kvenild, Stephan R. Orth
Journal: Journal of the American Society of Nephrology (2009)

Despite the high prevalence of chronic kidney disease (CKD), relatively few individuals with CKD progress to ESRD. A better understanding of the risk factors for progression could improve the classification system of CKD and strategies for screening. We analyzed data from 65,589 adults who participated in the Nord-Trøndelag Health (HUNT 2) Study (1995 to 1997) and found 124 patients who progressed to ESRD after 10.3 yr of follow-up. In multivariable survival analysis, estimated GFR (eGFR) and albuminuria were independently and strongly associated with progression to ESRD: Hazard ratios for eGFR 45 to 59, 30 to 44, and 15 to 29 ml/min per 1.73 m(2) were 6.7, 18.8, and 65.7, respectively (P < 0.001 for all), and for micro- and macroalbuminuria were 13.0 and 47.2 (P < 0.001 for both). Hypertension, diabetes, male gender, smoking, depression, obesity, cardiovascular disease, dyslipidemia, physical activity and education did not add predictive information. Time-dependent receiver operating characteristic analyses showed that considering both the urinary albumin/creatinine ratio and eGFR substantially improved diagnostic accuracy. Referral based on current stages 3 to 4 CKD (eGFR 15 to 59 ml/min per 1.73 m(2)) would include 4.7% of the general population and identify 69.4% of all individuals progressing to ESRD. Referral based on our classification system would include 1.4% of the general population without losing predictive power (i.e., it would detect 65.6% of all individuals progressing to ESRD). In conclusion, all levels of reduced eGFR should be complemented by quantification of urinary albumin to predict optimally progression to ESRD.
Pharmacokinetic Analysis and Phase 1 Study of MRX-1024 in Patients Treated with Radiation Therapy with or without Cisplatinum for Head and Neck Cancer
Authors: Daniel A. Hamstra, Avraham Eisbruch, Maddireddy U.R. Naidu, Gogula V. Ramana, Prasad Sunkara, Kathleen C.M. Campbell, Brian D. Ross, Alnawaz Rehemtulla
Journal: Clinical Cancer Research (2010)

Abstract Purpose: A previous study reported radiation protection from mucosal injury with D-methionine (D-met) in preclinical evaluation; therefore, the pharmacokinetics, safety, and utility of D-met were evaluated clinically. Experimental Design: The pharmacokinetics of D-met following oral administration of a bioavailable formulation (MRX-1024) was evaluated in normal volunteers. Subsequently, 25 patients were enrolled on a phase 1 study of MRX-1024 concurrent with radiation therapy (RT) with or without weekly cisplatinum. Toxicity and mucosal events were evaluated weekly. Results: Oral MRX-1024 resulted in rapid and dose-dependent increases in plasma D-met concentrations with a half-life of 3 hours. When administered concurrent with RT without chemotherapy, it was associated with a modest increase in grade 2 (two of six patients) and grade 3 (one of six patients) emesis. In those treated with MRX-1024 along with RT and weekly cisplatinum, there was no appreciable increase in emesis. Overall, five patients withdrew from the study due to emesis (four grade 2 and one grade 3). Only one incidence of dose-limiting toxicity (grade 3 emesis) was identified in 25 patients (4%). Finally, in 18 evaluable patients treated with MRX-1024 at 100 mg/kg twice daily (BID), the incidence of severe (grade 3) oral mucositis was 6% (1 of 18) with no grade 4 mucositis. Conclusions: There is a dose-dependent increase in D-met exposure following MRX-1024 administration at 50 and 100 mg/kg, and MRX-1024 is safe for use concurrent with combined radiation and chemotherapy. The observed rate of mucositis seems less than that for similar treatment regimens within the published literature. Clin Cancer Res; 16(9); 2666–76. ©2010 AACR.
Calcium and the heart: a question of life and death
Authors: Andrew R. Marks
Journal: Journal of Clinical Investigation (2003)

Nonstandard abbreviations used: sarcoplasmic reticulum (SR); nuclear factor of activated T cells (NFAT); protein kinase A (PKA); ryanodine receptor (RyR2); Ca 2+ /calmodulin-dependent protein kinase II (CaMKII); cardiac isoform of CaMKII