tbuckley/cabot-search huggingface dataset:
A novel G protein-coupled receptor mediating both vasopressin- and oxytocin-like functions of Lys-conopressin in Lymnaea stagnalis
Authors: R.E. van Kesteren, C.P. Tensen, A.B. Smit, J. van Minnen, P.F. van Soest, K.S. Kits, W. Meyerhof, D. Richter, H. van Heerikhuizen, E. Vreugdenhil, W.P.M. Geraerts
Journal: Neuron (1995)
Medical council shake up gets under way
Authors: O. Dyer
Journal: BMJ (2003)

The names of candidates for the General Medical Council's imminent elections were announced this week.

The newly constituted council will be reduced from 104 to 35 members in an effort to speed up decision making, but the proportion of lay members will increase.

All doctors currently registered with a UK address will receive ballot papers by mail. For the first time, doctors will be able to vote over the internet. The ballot opens on 28 March and closes …
Neuropilin–Semaphorin III/D-Mediated Chemorepulsive Signals Play a Crucial Role in Peripheral Nerve Projection in Mice
Authors: Takashi Kitsukawa, Masayuki Shimizu, Makoto Sanbo, Tatsumi Hirata, Masahiko Taniguchi, Yoko Bekku, Takeshi Yagi, Hajime Fujisawa
Journal: Neuron (1997)
Blocking IL-21 signaling ameliorates xenogeneic GVHD induced by human lymphocytes
Authors: Keli L. Hippen, Christoph Bucher, Dawn K. Schirm, Amanda M. Bearl, Ty Brender, Kathy A. Mink, Kimberly S. Waggie, Regis Peffault de Latour, Anne Janin, Julie M. Curtsinger, Stacey R. Dillon, Jeffrey S. Miller, Gerard Socie, Bruce R. Blazar
Journal: Blood (2011)
P1-04-03: The Effect of Survivin Downregulation on Radiosensitization of Breast Cancer Cell Lines Grown under Adherent and Stem Cell Promoting Culture Conditions.
Authors: BG Debeb, R Larson, W Xu, L Lacerda, JM Reuben, TA Buchholz, NT Ueno, WA Woodward
Journal: Cancer Research (2011)

Abstract Survivin, the smallest member of the inhibitor of apoptosis protein (IAP) family, is a bifunctional protein that has been implicated in both control of cell division and inhibition of apoptosis. Survivin has been shown to be involved in radiation resistance of various cancer types and its expression is increased by sublethal doses of irradiation in both differentiated and cancer stem cell (CSC) population. However, it is unknown whether suppression of survivin radiosensitizes the CSC population or diminishes its self renewal ability. Herein, we cloned the survivin dominant-negative mutant lacking a phosphorylation site (T34A) (Mesri et al., 2001 JCI) into the lentiviral LeGo vectors and assessed mammosphere formation and radiosensitization in MCF7, SUM149 and SUM159 cell lines grown under adherent or stem cell promoting conditions. We found an induction of survivin by western blotting in the dominant negative mutant (T34A)-transfected cell lines. Moreover, we observed a higher than two-fold increase in the Sub-G1 population as well as an increased Caspase 3 activity in the T34A-transfected SUM149 and SUM159 cells compared to control cells indicating an anti-apoptotic function of survivin. We also found that T34A-transfected cells showed a 1.5 to 2-fold decrease in the number of mammospheres compared to the control-transfected cells. Furthermore, T34A-transfected cells showed radiosensitization in adherent cells from SUM149 and SUM159 cells but no effect was observed in MCF7 cells. However, no radiosensitization was observed in stem cell promoting culture conditions with increasing doses of radiation in all tested cell lines. This indicates that the widely used standard clonogenic assays do not optimally select anti-CSC agents and that targeted therapies should be specifically tested for their activity against the CSC population. Further functional endpoint studies will be conducted to validate the in vitro findings. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-04-03.
A PROCEDURE FOR FACILITATING THE EXPERIMENTAL TESTING OF RABIES.
Authors: A. P. OHLMACHER
Journal: JAMA (1904)

In the course of a considerable number of cases in which our laboratory has been called on to make a diagnosis of rabies in dogs or cattle, I have found it possible to expedite the examination and minimize the danger to the operator by a simple method which is not described, and which is original if not novel. As is well known to those interested in the experimental study of hydrophobia, the material for examination which usually finds its way to a laboratory consists either of the carcass or the head and neck of a dog or other suspected animal. To prosecute the requisite tests one must obtain certain ganglia for making the rapid histologic examination (the Van Gehuchten-Nelis test), and a portion of the brain or cord, preferably of the medulla, for experimental inoculation. Ordinarily the brain of the suspected animal is exposed by piecemeal clipping off the dome of the skull and the arches of the vertebra by means of bone forceps.
Androgen metabolism by isolated human axillary apocrine glands in hidradenitis suppurativa
Authors: J. H. BARTH, T. KEALEY
Journal: British Journal of Dermatology (1991)

Androgen metabolism was investigated in normal human apocrine glands and in those isolated from age-matched patients with hidradenitis suppurativa. Axillary glands were isolated by shearing and androgen interconverting enzyme activities were measured in cell-free homogenates by incubation with [3H] dehydroepiandrosterone, [3H] androstenedione and [3H] testosterone. The activities (pmol/mg protein/min: mean + SEM) of 3 beta-hydroxysteroid dehydrogenase delta 4-5-isomerase (10.0 +/- 1.2 vs. 5.3 +/- 0.5: n = 5) and 17 beta-hydroxysteroid dehydrogenase (58.1 +/- 4.5 vs. 35.7 +/- 5.2: n = 5) were significantly lower (P less than 0.005) in hidradenitis suppurativa, whereas 5 alpha-reductase activity (12.5 +/- 2.3 vs. 12.5 +/- 2.0: n = 5) was similar. This report suggests that hidradenitis suppurativa cannot be attributed to exaggerated activities of end-organ androgen interconverting enzymes.
Popeye proteins: muscle for the aging sinus node
Authors: Bastiaan J. Boukens, Vincent M. Christoffels
Journal: Journal of Clinical Investigation (2012)

The electrical impulses that dictate the rhythm of the heartbeat in normal situations and during exercise or stress are initiated by a small number of sinus node pacemaker cells. Senescence and dysfunction of the sinus node affects many people later in life, causing physiologically inappropriate heart rates, but the underlying mechanisms are not well understood. In this issue of the JCI, Froese and colleagues show that deficiency in either Popeye domain containing 1 (Popdc1) or Popdc2 leads to sinus node dysfunction under stressed conditions in aged mice. The mechanism reported to underlie the effects of Popdc1/2 deficiency in mice may cause the stress-induced sinus node dysfunction found in many aged individuals and may point to new strategies for therapeutic intervention.
Effects of Pulmonary Venous Flow Direction on Mitral Regurgitation Jet Area as Imaged by Color Doppler Flow Mapping
Authors: Katsufumi Mizushige, Takahiro Shiota, Juliana Paik, Gerard Griever, Marianne R. Depp, Arnaldo Passafini, Robin Shandas, Anthony N. DeMaria, David J. Sahn
Journal: Circulation (1995)

Background Although the effects of adjacent walls and left atrial pressure on mitral regurgitation (MR) jet area imaged by color Doppler have been examined, few data exist regarding the influence of pulmonary venous (PV) filling flow on regurgitant jets. Therefore, we designed a left atrial model to examine the relation between PV flow direction and MR jet area. Methods and Results The left atrial chamber (7.6 cm in diameter) was built with a PV inflow (1.0 cm in diameter) and mitral valve regurgitant orifice in the same plane. The MR jet was simulated as fixed in volume and velocity (3.5 m/s) and directed with a pulsatile pump into the left atrial model. PV flow with a constant velocity (30 cm/s) was driven by gravity (83 cm H 2 O). With left atrial mean pressure at either 10, 30, or 50 mm Hg, four flow patterns were examined: (1) PV flow away from the mitral valve, MR jet toward the pulmonary vein; (2) PV flow toward the mitral valve, MR jet toward the pulmonary vein; (3) PV flow away from the mitral valve, MR jet away from the pulmonary vein; and (4) PV flow toward the mitral valve, MR jet away from the pulmonary vein. MR color Doppler images were recorded with a 3.5-mHz frequency transducer and at 7-kHz pulse repetition frequency. For each condition, we compared jet area, length, and width of the MR signal. MR jet areas for conditions 3 and 4 were larger at 10 mm Hg than at 30 or 50 mm Hg left atrial pressure. Especially at the lower pressures, PV flow diminished the MR jet area in condition 4 compared with that in condition 3, such that MR jets were smaller in condition 4. In conditions 1 and 2, the jets were imaged at an oblique angle and were smaller than in conditions 3 and 4 ( P &lt;.001), but they were not significantly different from each other as imaged. Conclusions In this model, factors including the direction of PV flow, the direction of MR as relates to the angle of interrogation, and the level of left atrial pressure influenced the size of MR jets. The effect of PV flow direction was diminished by increased left atrial pressure. PV flow directed away from the mitral valve was associated with larger MR jets than when PV flow was directed toward it (condition 4), probably because of jet distortion and flattening.
REPORT ON OPERATIVE TREATMENT OF GRAVES' DISEASE.
Authors: T. C. WITHERSPOON
Journal: JAMA (1903)

Case1.—In April, 1895, a patient presented herself for treatment suffering from a well-developed Graves' disease. Exophthalmia was not marked, but the cardiac frequency and the thyroid enlargement was present. Tremor, loss of flesh and bowel symptoms made the case one of undoubted Graves' disease. She submitted to partial thyroidectomy under chloroform and made a nice recovery. Two years afterward I received word from her through a friend that she was well and strong, able to attend her duties and suffering none of the former symptoms. Case2.—In 1898 a patient was sent me who suffered from a similar condition. She was 52 years of age, very thin, having lost a great many pounds of flesh, suffered from recurring diarrhea and was very weak, practically bed ridden. The pulse rate was 140 to 160, the thyroid very large and vascular, exophthalmia not marked. The right lobe being the larger was
The Treatment of Psoriasis
Authors: Howard P. Baden
Journal: New England Journal of Medicine (1963)

PSORIASIS is a familial disease of the skin characterized clinically by an increased production of abnormal scales, resulting from a marked hyperplasia of immature epidermal cells.1 2 3 4 5 6 7 8 9 10 Further evidence of the rapid rate of cell division is the elevated serum uric acid level and the large uric acid pool, reflecting the increased turnover of nucleic acids.Biochemical studies have revealed the incomplete removal of these acids, soluble proteins and other constituents that are normally degraded during keratinization.Psoriasis is a common condition, occurring in one to two per cent of the population. The average age of onset is in the second . . .
Influence of age on response to ipratropium and salbutamol in asthma.
Authors: M I Ullah, G B Newman, K B Saunders
Journal: Thorax (1981)

We studied the differential response to inhaled salbutamol and ipratropium of 29 asthmatic patients, 18 intrinsic, 11 extrinsic, using peak expiratory flow rate (PEFR), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC). Thirty minutes after a theoretically maximally bronchodilating dose of salbutamol (400 microgram) or ipratropium (80 microgram), second doses frequently caused further bronchodilatation. We suspect that second doses may reach bronchi untouched by the first inhalation. Analysis of variance showed a powerful intrinsic versus extrinsic effect, and there were clearly differences between patients in their response to treatment (patient versus drug interaction) but these differences were not removed by dividing the patients into intrinsic and extrinsic groups. Results for the group as a whole favoured salbutamol, but examination of individual results by a pattern-recognition technique showed ipratropium equally effective in eight patients and more effective in three. All patients with a definite predominant salbutamol response were less than 40 years old. The response to salbutamol declined significantly with age, whereas that to ipratropium did not. In general in patients aged less than 40 years salbutamol is the drug of choice. With advancing age, and the apparent decline of beta-adrenergic responsiveness, the initially comparatively small response to ipratropium becomes relatively more important and may predominate. In older patients ipratropium, or continued therapy with both drugs, may be preferable.
Hyperbaric Oxygen Therapy
Authors: Robert Ingle
Journal: JAMA (1990)

<h3>To the Editor.—</h3> I was disturbed by the recent review on hyperbaric oxygen (HBO) therapy.<sup>1</sup>As the former director of several ongoing Air Force human clinical trials of HBO therapy for diabetic wound healing and chronic osteomyelitis, I believe that the article did not sufficiently emphasize the experimental nature of HBO therapy in wound healing. Further, I found that the review closely followed the advocacy style of the Undersea and Hyperbaric Medical Society,<sup>2</sup>even down to its inaccurate references (eg, the article by Van Unnik does not say that 250 mm Hg of oxygen tension alters Clostridial alpha toxin production; rather, he concludes that "the production of alpha toxin is inhibited during treatment with oxygen at a pressure of 3 atmospheres absolute but not at a pressure of 2 atmospheres"). The brief review on carbon monoxide poisoning is a further example of this advocacy bias: the only
Management of the Pregnant, Insulin-Dependent Diabetic Woman
Authors: Lois Jovanovic, Charles M Peterson
Journal: Diabetes Care (1980)

An intensive care program was offered to all insulin-dependent, pregnant diabetic women who presented to The New York Hospital Obstetrical Clinic in their eighth week or less of gestation. The patients were hospitalized for 1 wk to normalize their blood glucose and to teach the technique of self-monitored glucose determination, diet and exchange lists, and the method to titrate insulin according to the blood glucose determination. The mean blood glucose for the first 10 patients accepted to the program was 169 mg/dl at the start of the program with a mean hemoglobin A1c of 9.4% for the group (normal &amp;lt; 5.5%) and glucosuria up to 50 g/24 h. After discharge, mean glucose was 91 mg/dl, and urinary glucose excretion was 1.4 g/24 h. HbA1c fell into the normal range 5 wk after normoglycemia was achieved (3.4%) (nl &amp;lt; 5.5%). Normoglycemia was maintained as outpatients until 3 wk before delivery when the patients were readmitted for tests of fetal well-being. Mean weight gain for the mothers was 12.2 kg. Mean glucose at delivery was 87 mg/dl and HbA1c was 3%. Hormonal profiles (hCG, hPRL, estrogens, progesterone, hPL) normalized after normoglycemia was achieved and remained normal until delivery. Mean gestational age at time of delivery was 38.8 wk with a mean infant birth weight of 2988 g. No infant manifested hypoglycemia, hypocalcemia, erythremia, or respiratory disease. The use of self-monitored blood glucose allows for optimal care of the insulin-dependent, pregnant diabetic woman while she remains at home with her family.
Study linking chronic fatigue syndrome with retrovirus is partially retracted
Authors: A. Sayburn
Journal: BMJ (2011)

The authors of a controversial paper published in Science that linked chronic fatigue syndrome to a mouse retrovirus have partially retracted their findings, admitting that some of their samples were contaminated. At the same time new research casts further doubt on the original findings.

However, the study’s authors, led by Vincent Lombardi at the Whittemore Peterson Institute in Reno, Nevada, say that their research ( Science 2009;326:585, doi:10.1126/science.1179052) didn’t rely solely on the data they are retracting.

The paper created much interest when it was published in 2009. It seemed to show that 67% of a group of patients with chronic fatigue syndrome but only 3.7% of healthy controls showed signs of infection with xenotropic murine leukaemia virus related virus (XMRV).

The study was welcomed by patients’ groups, who saw it as a validation of the clinical basis for the syndrome and as an area for researching a cure. Antiretroviral drugs were proposed as a potential …
Early Environmental Exposures and Intracellular Th1/Th2 Cytokine Profiles in 24-Month-Old Children Living in an Agricultural Area
Authors: Paurene Duramad, Kim Harley, Michael Lipsett, Asa Bradman, Brenda Eskenazi, Nina T. Holland, Ira B. Tager
Journal: Environmental Health Perspectives (2006)

BackgroundChildren who reside in agricultural settings are potentially exposed to higher levels of organophosphate (OP) pesticides, endotoxin, and allergens than their urban counterparts. Endotoxin and allergens stimulate maturation of the immune response in early childhood, but little is known about the effect of exposures to OPs or to the three combined.ObjectivesIn this study, we investigated the relationships between these exposures and T-helper 1 (Th1) and T-helper 2 (Th2) cytokines, biomarkers of allergic asthma, in the subjects of CHAMA-COS (Center for the Health Assessment of Mothers and Children of Salinas), a longitudinal birth cohort in Salinas Valley, California. Exposures were ascertained by interviewer-administered questionnaires and by home visits, and clinical diagnoses were abstracted from medical records. Blood samples were collected at 12 and 24 months of age and analyzed for Th1/Th2 status by flow cytometric detection of intracellular interferon-γ/interleukin-4 cytokine expression.FindingsMean Th2 levels were significantly higher in children with doctor-diagnosed asthma and children with wheezing at 2 years of age. In a multiple linear regression model, exclusive breast-feeding at 1 month and pet ownership were associated with 35.3% (p < 0.01) and 34.5% (p = 0.01) increases in Th1, respectively. Maternal agricultural work and presence of gas stove in the home were associated with a 25.9% increase (p = 0.04) and 46.5% increase (p < 0.01) in Th2, respectively.ConclusionsAsthma and wheeze outcomes in children at 24 months of age are associated with elevated Th2 status in children at an early age. Our data further suggest that early exposures to an agricultural environment, breast-feeding, pets, and gas stoves affect the development of children's Th1/Th2 immune response.
DNA damage-inducible genes as biomarkers for exposures to environmental agents.
Authors: N F Johnson, T R Carpenter, R J Jaramillo, T A Liberati
Journal: Environmental Health Perspectives (1997)

A biodosimetric approach to determine alpha-particle dose to the respiratory tract epithelium from known exposures to radon has been developed in the rat. Cytotoxicity assays have been used to obtain dose-conversion factors for cumulative exposures typical of those encountered by underground uranium miners. However, this approach is not sensitive enough to derive dose-conversion factors for indoor radon exposures. The expression of DNA damage-inducible genes is being investigated as a biomarker of exposure to radon progeny. Exposure of cultures of A549 cells to alpha particles resulted in an increase in the protein levels of the DNA damage-inducible genes, p53, Cip1, and Gadd45. These protein changes were associated with a transient arrest of cells passing through the cell cycle. This arrest was typified by an increase in the number of cells in the G1 and G2 phases and a decrease in the number of cells in the S phase. The effect of inhaled alpha particles (radon progeny) in rats was examined in the epithelial cells of the lateral well of the anterior nasal cavity. Exposures to radon progeny resulted in a significant increase in the number of cells in the G1 phase and a decrease in the number of cells in the S phase. These cell-cycle changes were concomitant with an increase in the number of cells containing DNA strand breaks. These results suggest a commonality between cell-cycle events in vitro and in vivo following exposure to ionizing radiation. In addition to ionizing radiation, A549 cells were exposed to 4-nitroquinoline-1-oxide, methyl methanesulphonate, crocidolite asbestos, and glass microfiber. These studies showed that physical and chemical agents induce different expression patterns of p53, Cip1, and Gadd153 proteins and they could be used to discriminate between toxic and nontoxic materials such as asbestos and glass microfiber. The measurement of gene expression in A549 cells may provide a means to identify a broad spectrum of physical and chemical toxicants encountered in the environment.
Effects of Modulation of Basic Fibroblast Growth Factor on Tumor Growth In Vivo
Authors: J. L. Gross, W. F. Herblin, B. A. Dusak, P. Czerniak, M. D. Diamond, T. Sun, K. Eidsvoog, D. L. Dexter, A. Yayon
Journal: JNCI Journal of the National Cancer Institute (1993)

Recombinant human basic fibroblast growth factor (rHu-bFGF) is known to stimulate proliferation in some tumor cells and to modulate tumor vascularization.The purpose of this study was to examine the possible role of this agent in the development of tumors. The study was designed to determine the effects of modulating bFGF activity in vivo in tumor models from cell lines with different responses to bFGF and with different content and receptor levels of bFGF.Two tumor cell lines (human DLD-2 colon carcinoma and rat C6 glioma) were characterized for bFGF content and bFGF receptor levels by Western blot analysis in cultured cells and by studies of [125I]rHu-bFGF binding to sections from xenografts grown in nude mice. Tumor cell proliferation was monitored after treatment with rHu-bFGF or the DG2 or DE6 IgG monoclonal antibody to rHu-bFGF in culture and in vivo.C6 cells exhibited 7800 high-affinity receptors for rHu-bFGF per cell (dissociation constant [Kd] = 46 pM), while DLD-2 cells lacked high-affinity receptors. rHu-bFGF stimulated [3H]thymidine uptake by C6 cells, but the addition of DG2 IgG prevented this stimulation; rHu-bFGF had no effect on [3H]thymidine incorporation by DLD-2 cells. C6 cells had higher levels of immunoreactive bFGF than did DLD-2 cells. The xenografts from both cell lines exhibited high-affinity [125I]rHu-bFGF binding that was concentrated on vascular-like structures. rHu-bFGF at a dosage of 0.25 mg/kg given intraperitoneally daily for 18 days caused a twofold increase in DLD-2 tumor weight but had little effect on the growth of C6 xenografts. In contrast, daily intravenous injections of DG2 IgG given to mice had no effect on DLD-2 tumor growth but reduced growth of C6 tumors by approximately 30%--a statistically significant difference.The addition of exogenous rHu-bFGF or of a neutralizing antibody resulted in significant alterations in tumor growth in vivo, which were specific for tumor type and bFGF characteristics. While some of these effects may be mediated by the bFGF-responsive endothelial cells of the tumor vasculature (DLD-2 colon carcinoma), others may result from inhibition of bFGF-dependent tumor cell proliferation (C6 glioma).Studies that measure tumor blood flow are necessary to confirm that these effects are mediated by changes in tumor vasculature.
Typhus Fever in Great Britain
Authors: A. P. Agnew, W. B. Kyles
Journal: BMJ (1944)

The reactions of the patient's serum and cells during and after the disease are described.The presence of a heat-stable auto-agglutinin and auto- haemolysin and an auto-agglutinogen is demonstrated.The presence of an autohaemolysinogen is suggested.Changes in the granulocytes are reported and their aetiological significance is indicatecd.I wish to thank Dr. J. W.