tbuckley/cabot-search huggingface dataset:
Bystander effect caused by suicide gene expression indicates the feasibility of gene therapy for hepatocellular carcinoma
Authors: Shigeki Kuriyama, Toshiya Nakatani, Kazuhiro Masui, Takemi Sakamoto, Kentarou Tominaga, Masahide Yoshikawa, Hiroshi Fukui, Kazuhiro Ikenaka, Tadasu Tsujii
Journal: Hepatology (1995)

In the field of gene therapy using retroviral vectors, it appears impossible to introduce a foreign gene into all target cells. Therefore adjacent cell killing, the socalled bystander effect, caused by genetically modified cells provides therapeutic advantages for gene therapy against cancers. We retrovirally transduced the herpes simplex virus thymidine kinase (HSV-tk) gene into murine and rat hepatocellular carcinoma (HCC) cells. These HSV-tk gene-transduced HCC cells were cocultured with the corresponding parental cells in the presence of ganciclovir, at a concentration not at all cytotoxic to the parental cells. When parental HCC cells were cocultured with their HSV-tk gene-transduced counterparts at a high density at which most cells were in contact with one another, they were markedly eliminated. Conversely, when cocultured at a low density at which none of the cells were in contact, a weak but statistically significant bystander effect was observed. Addition of lysates of HSV-tk gene-transduced cells in the presence of ganciclovir did not cause and killing of parental cells. Furthermore, media conditioned by transduced cells with ganciclovir exhibited weak cytotoxic effects on parental cells. These results indicate that cell-cell contact plays a major causative role in the bystander effect and that minor contributors to this phenomenon are some cytotoxic substance released from transduced cells. Importantly, the bystander effect was induced in vivo as well as in vitro. When mixtures of transduced and untransduced HCC cells were implanted into the flank region of mice, intraperitoneal ganciclovir administration considerably inhibited tumor development, indicating the feasibility of gene therapy with HSV-tk gene and ganciclovir against HCC.
Selection of patients for biological standardization as exemplified by standardization of mugwort, goosefoot and English plantain pollen allergen extracts/preparations
Authors: S. Dreborg, I. Sjögren, N. E. Eriksson, R. Einarsson
Journal: Allergy (1987)

The biological activity of a partly purified, biochemically/immunochemically characterized mugwort pollen allergen preparation and crude pollen extracts of mugwort, goosefoot and English plantain was determined by means of skin prick test (SPT). The patient inclusion criteria with mugwort were a well-defined positive clinical history and a positive SPT. Symptoms related to goosefoot/English plantain pollens are difficult to define, as these weeds flower during the grass pollen season. Thus patients tested with these allergens did not fulfill the most important inclusion criterion for so-called biological standardization. To elicit a wheal of the same size as that produced by histamine 1 mg/ml required 100 to 10,000 times more material from these weeds, than from mugwort and other pollen allergen extracts investigated earlier. One thousand Biological Units/ml (BU/ml) corresponded to 8.3 micrograms dry weight (dw/ml) of the crude and 1.8 micrograms dw/ml of the purified mugwort pollen allergen preparation. Only 7/22 goosefoot-and English plantain-tested patients were positive at conjunctival or nasal challenge. All three weeds showed a similar composition with 5-10 allergens by CIE/CRIE analysis and 10-13 by immunoblotting analysis. One dominating allergen (approx. 15,000 d), could be identified for each weed species by protein gel blot after separation by SDS g-PAGE. There was no other explanation for the difference in biological activity than the criteria of selection. If there is no obvious clinical history, which is the main patient inclusion criterion in biological standardization, then additional criteria should be used.
Systems Biology and Birth Defects Prevention: Blockade of the Glucocorticoid Receptor Prevents Arsenic-Induced Birth Defects
Authors: Bhavesh K. Ahir, Alison P. Sanders, Julia E. Rager, Rebecca C. Fry
Journal: Environmental Health Perspectives (2013)

The biological mechanisms by which environmental metals are associated with birth defects are largely unknown. Systems biology-based approaches may help to identify key pathways that mediate metal-induced birth defects as well as potential targets for prevention.First, we applied a novel computational approach to identify a prioritized biological pathway that associates metals with birth defects. Second, in a laboratory setting, we sought to determine whether inhibition of the identified pathway prevents developmental defects.Seven environmental metals were selected for inclusion in the computational analysis: arsenic, cadmium, chromium, lead, mercury, nickel, and selenium. We used an in silico strategy to predict genes and pathways associated with both metal exposure and developmental defects. The most significant pathway was identified and tested using an in ovo whole chick embryo culture assay. We further evaluated the role of the pathway as a mediator of metal-induced toxicity using the in vitro midbrain micromass culture assay.The glucocorticoid receptor pathway was computationally predicted to be a key mediator of multiple metal-induced birth defects. In the chick embryo model, structural malformations induced by inorganic arsenic (iAs) were prevented when signaling of the glucocorticoid receptor pathway was inhibited. Further, glucocorticoid receptor inhibition demonstrated partial to complete protection from both iAs- and cadmium-induced neurodevelopmental toxicity in vitro.Our findings highlight a novel approach to computationally identify a targeted biological pathway for examining birth defects prevention.
Human Splanchnic and Forearm Vasoconstrictor Responses to Reductions of Right Atrial and Aortic Pressures
Authors: JOHN M. JOHNSON, LORING B. ROWELL, MANFRED NIEDERBERGER, MARTIN M. EISMAN
Journal: Circulation Research (1974)

Regional vascular responses to gradual reductions in right atrial pressure and aortic pressure were investigated in nine men. In each study, lower body negative pressure was applied in a ramp of -1 mm Hg/min for 40-50 minutes. During the range from control to -20 mm Hg, right atrial pressure (4 studies) fell from 4.2 mm Hg to -0.6 mm Hg; heart rate was slightly reduced (2 beats/min), and aortic mean pressure and pulse pressure (6 studies) were unchanged. The maximal rate of rise of aortic pressure showed no consistent trends. Forearm blood flow (30 studies) fell with the onset of lower body negative pressure and reached 67% of the control value by -20 mm Hg. Splanchnic blood flow (14 studies) was significantly reduced by -7 mm Hg and fell to 89% of control by -20 mm Hg. During the range from -20 to -50 mm Hg, right atrial pressure continued to fall. Aortic mean pressure fell slightly or was unchanged in four subjects and fell dramatically at -35 mm Hg in two subjects. Aortic pulse pressure began to fall at about -20 mm Hg and fell linearly thereafter. Heart rate paralleled aortic pulse pressure ( r = -0.86 to -0.93). Forearm blood flow fell to 55% and splanchnic blood flow fell to 65% of control at -50 mm Hg. Thus, significant vasoconstriction occurred without measurable change in arterial blood pressure. We concluded that low-pressure baroreceptors, presumably in the cardiopulmonary region, initiate splanchnic and forearm vasoconstriction with more pronounced vasoconstriction occurring in the forearm.
Nebivolol: A Third-Generation β-Blocker That Augments Vascular Nitric Oxide Release
Authors: Martijn A. W. Broeders, Pieter A. Doevendans, Bas C. A. M. Bekkers, Ronald Bronsaer, Erik van Gorsel, Johan W. M. Heemskerk, Mirjam G. A. oude Egbrink, Eric van Breda, Robert S. Reneman, Rien van der Zee
Journal: Circulation (2000)

Background —Nebivolol is a β 1 -selective adrenergic receptor antagonist with proposed nitric oxide (NO)–mediated vasodilating properties in humans. In this study, we explored whether nebivolol indeed induces NO production and, if so, by what mechanism. We hypothesized that not nebivolol itself but rather its metabolites augment NO production. Methods and Results —Mouse thoracic aorta segments were bathed in an organ chamber. Administration of nebivolol did not affect NO production. When nebivolol was allowed to metabolize in vivo in mice, addition of plasma of these mice caused a sustained 2-fold increase in NO release. Interestingly, coadministration of a selective β 2 -adrenergic receptor antagonist (butoxamine) prevented the response. Immunohistochemistry and Western blot analysis demonstrated the presence of β 2 - but not β 1 -adrenergic receptors on endothelial cells. In the absence of calcium, metabolized nebivolol failed to increase NO production, suggesting a role for calcium-dependent NO synthase. With digital fluorescence imaging, a rapid and sustained rise in endothelial cytosolic free Ca 2+ concentration was observed after administration of metabolized nebivolol, which also was abrogated by butoxamine pretreatment. Conclusions —In vivo metabolized nebivolol increases vascular NO production. This phenomenon involves endothelial β 2 -adrenergic receptor ligation, with a subsequent rise in endothelial free [Ca 2+ ] i and endothelial NO synthase–dependent NO production. This may be an important mechanism underlying the nebivolol-induced, NO-mediated arterial dilation in humans.
Firearm Injury Prevention
Authors: Gary F. Kuhns
Journal: Annals of Internal Medicine (1998)

Letters15 August 1998Firearm Injury PreventionGary F. Kuhns, MDGary F. Kuhns, MDCarolina FirstCare; Charleston, SC 29414Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-4-199808150-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Although I thought that the American College of Physicians (ACP) had exhausted its inventory of socialist ideas with its pronouncements on health care reform, imagine my surprise upon receiving the 1 February 1998 issue of Annals. A small and contrived “survey” of physicians [1], many ill-formed on gun issues, was used to justify the release of a position paper [2] that regurgitated almost verbatim the lunacies of the hardcore antigun lobby. Unfortunately, the word limit of the Letters section prevents my rebutting this absurdly naive document in detail. By use of many studies that have been discredited ...References1. Cassel CK, Nelson EA, Smith TW, Schwab CW, Barlow B, Gary NE. Internists' and surgeons' attitudes toward guns and firearm injury prevention. Ann Intern Med. 1998; 128:224-30. Google Scholar2. Firearm injury prevention. American College of Physicians. Ann Intern Med. 1998; 128:236-41. Google Scholar3. Suter EA. Guns in the medical literature-a failure of peer review. J Med Assoc Ga. 1994; 83:133-48. Google Scholar4. Kleck G. Guns and self-protection. J Med Assoc Ga. 1994; 83:42. Google Scholar5. Faria M Jr. Medical Warrior: Fighting Corporate Socialized Medicine. Macon, GA: Hacienda Publishing; 1997. Google Scholar Author, Article, and Disclosure InformationAffiliations: Carolina FirstCare; Charleston, SC 29414 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 August 1998Volume 129, Issue 4Page: 335-336KeywordsFirearm injuriesHealth carePsychiatry and mental healthSafety Issue Published: 15 August 1998 CopyrightCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Thyroid thermogenesis. Relationships between Na+-dependent respiration and Na+ + K+-adenosine triphosphatase activity in rat skeletal muscle.
Authors: Y Asano, U A Liberman, I S Edelman
Journal: Journal of Clinical Investigation (1976)

The effect of thyroid status on QO2, QO2 (t) and NaK-ATPase activity was examined in rat skeletal muscle. QO2(t) (i.e. Na+-transport-dependent respiration) was estimated with ouabain or Na+-free media supplemented with K+. In contrast to the effects of ouabain on ion composition, intracellular K+ was maintained at about 125 meq/liter, and intracellular Na+ was almost nil in the Na+-free media. The estimates of QO2(t) were independent of the considerable differences in tissue ion concentrations. The increase in QO2(t) account for 47% of the increase in QO2 in the transition from the hypothyroid to the euthyroid state and 84% of the increase in the transition from the euthyroid to the hyperthyroid state. Surgical thyroidectomy lowered NaK-ATPase activity of the microsomal fraction (expressed per milligram protein) 32%; injections of triodothyronine (T3) increased this activity 75% in initially hypothyroid rats and 26% in initially euthyroid rats. Thyroidectomy was attended by significant falls in serum Ca and Pi concentrations. Administration of T3 resulted in further declines in serum Ca and marked increases in serum Ps concentrations. Similar effects were seen in 131I-treated rats, but the magnitude of the declines in serum Ca were less. The effects of T3 on QO2, QO2(t), and NaK-ATPase activity of skeletal muscle were indistinguishable in the 131I-ablated and surgically thyroidectomized rats. In thyroidectomized or euthyroid rats given repeated doses of T3, QO2(t) and NaA-ATPase activity increased proportionately. In thyroidectomized rats injected with single doses of T3, either 10, 50, or 250 mug/100 g body wt, QO2(t) increased linearly with NaK-ATPase activity. The kinetics of the NaK-ATPase activity was assessed with an ATP-generating system. T3 elicited a significant increase in Vmax with no change in Km for ATP.
Cadmium Levels in Urine and Mortality among U.S. Adults
Authors: Andy Menke, Paul Muntner, Ellen K. Silbergeld, Elizabeth A. Platz, Eliseo Guallar
Journal: Environmental Health Perspectives (2008)

Cadmium exposure has been associated with increased all-cause, cancer, and cardiovascular disease mortality. However, studies investigating this association have included participants with considerably higher levels of cadmium than those found in the general population.
Constitutive activity of signal transducer and activator of transcription 3 protein in acute myeloid leukemia blasts is associated with short disease-free survival
Authors: Mustafa Benekli, Zheng Xia, Kathleen A. Donohue, Laurie A. Ford, Lynda A. Pixley, Maria R. Baer, Heinz Baumann, Meir Wetzler
Journal: Blood (2002)
Disseminated CMV Infection
Authors: Donald P. Kotler
Journal: JAMA (1985)

To the Editor.—  The mucous membranes appear to be particularly vulnerable to opportunistic infections in patients with the acquired immunodeficiency syndrome (AIDS). Such infections may arise either from the external environment or by extension from a systemic focus. We wish to report a patient with AIDS and a chronic rhinitis and sinusitis due to cytomegalovirus (CMV) that led to an erroneous impression of CMV pneumonitis.  Report of a Case.—  A 33-year-old homosexual man was evaluated for interstitial pneumonitis. There was a history of fever, weight loss, intermittent diarrhea, anorectal herpes infection, and previous admissions for an unspecified pneumonia and staphylococcal sepsis—the latter felt to be caused by nasal vestibulitis. On the second hospital day, pneumocystis pneumonia was disgnosed by bronchoalveolar lavage. No biopsies were performed.  The patient was treated with trimethoprim sulfate and had clinical resolution of symptoms, although temperatures to 38.8 °C continued. The patient was anemic and lymphopenic.
The Surgical Treatment of Haemorrhoids
Authors: W. Whitehead
Journal: BMJ (1882)

it would not be better to retain our nineteen examining bodies, and try whether we cannot induce them to compete with one another as to which should have the highest character, do most to improve educa- tion, and so elevate our professional character.This it is that seems to me to be the all important object at which we should aim, to stimu'ate our examining bodies to compete as to which should have the highest character.IIitherto the competition has, it is said, been as to which could make its examinations most easy, and so attract candi(dates to its portals.This may be true of some; but when such a charge is brought against us, we can lift our heads with pride and refute it by pointing, not to one, but to the majority of our
A novel panel of blood markers to assess the degree of liver fibrosis
Authors: Paul Calès, Frédéric Oberti, Sophie Michalak, Isabelle Hubert‐Fouchard, Marie‐Christine Rousselet, Anselme Konaté, Yves Gallois, Catherine Ternisien, Alain Chevailler, Françoise Lunel
Journal: Hepatology (2005)

The objective was to develop new blood tests to characterize different fibrosis parameters in viral and alcoholic chronic liver diseases. Measurements included 51 blood markers and Fibrotest, Fibrospect, ELFG, APRI, and Forns scores. The clinically significant fibrosis was evaluated via Metavir staging (F2-F4), and image analysis was used to determine the area of fibrosis. In an exploratory step in 383 patients with viral hepatitis, the area under the receiving operator characteristic (AUROC) curve for stages F2-F4 in a test termed the "Fibrometer" test combining platelets, prothrombin index, aspartate aminotransferase, α2-macroglobulin (A2M), hyaluronate, urea, and age was 0.883 compared with 0.808 for the Fibrotest (P = .01), 0.820 for the Forns test (P = .005), and 0.794 for the APRI test (P < 10−4). The Fibrometer AUROC curve was 0.892 in the validating step in 120 patients. The AUROC curve for stages F2-F4 in a test combining prothrombin index, A2M, hyaluronate, and age was 0.962 in 95 patients with alcoholic liver diseases. The area of fibrosis was estimated in viral hepatitis by testing for hyaluronate, γ-glutamyltransferase, bilirubin, platelets, and apolipoprotein A1 (aR2 = 0.645), and in alcoholic liver diseases by testing for hyaluronate, prothrombin index, A2M, and platelets (aR2 = 0.836). In conclusion, the pathological staging and area of liver fibrosis can be estimated using different combinations of blood markers in viral and alcoholic liver diseases. Whereas the Fibrometer has a high diagnostic accuracy for clinically significant fibrosis, blood tests for the area of liver fibrosis provide a quantitative estimation of the amount of fibrosis, which is especially useful in cirrhosis. (HEPATOLOGY 2005.)
Clinical academic staff threaten sanctions over pay GPs welcome voluntary nature of white paper GMC president explains performance assessment College launches new course for surgical trainees
Authors: L. Beecham
Journal: BMJ (1996)

# Clinical academic staff threaten sanctions over pay {#article-title-2}

University employers have told clinical academic staff that they cannot afford to match their pay to that of hospital doctors in the NHS unless the government provides additional funding. The government has refused and the doctors have been offered a pay award of 1.5%, the same increase as offered to other groups of university staff.

The profession has declined the universities' offer, and the BMA council resolved last week that if the Universities and Colleges Employers Association has not agreed to translate the award by the time of its January meeting clinical academic appointments in universities and medical schools will be included in the Important Notice in the BMJ. This advises members to contact the secretary of the BMA before applying for such posts.

The government accepted the recommendation of the Review Body on Doctors' and Dentists' Remuneration in its 1996 report for an average increase for NHS doctors of 3.8%. Since 1979 the universities have been able to maintain broad comparability with government support. This year not only did the government refuse extra funds, but it cut university funding by 2.1%. The cost of maintaining pay parity is £4.8m.

The chairman of the Clinical Academic Staff Salaries Committee, Professor Philip Love, said that he had been pressing ministers to stand by the commitment given in 1986 that whenever there was a shortfall in university funding compared with the NHS extra cash would be provided to enable pay parity to be maintained. “Ministers have refused and do not seem to understand the …
Risk of perforation during endoscopic submucosal dissection using latest insulation-tipped diathermic knife (IT knife-2)
Authors: S. Con, I. Oda, H. Suzuki, C. Kusano, S. Kiriyama, T. Gotoda
Journal: Endoscopy (2009)

Endoscopic submucosal dissection (ESD) enables en bloc resection of lesions regardless of tumor size or location. The insulation-tipped (IT) diathermic knife (Olympus Medical Systems Corp., Tokyo, Japan) is a proven endoscopic device for ESD [1] [2]. ESD gastric perforations using the IT knife usually happen during submucosal dissection [3]. However, we present an ESD perforation case that occurred when an IT knife-2, an improved version of the IT knife [4], was being used for circumferential mucosal incision.
CRITICAL EVALUATION OF THE DIAGNOSTIC USEFULNESS OF In-111 LABELED WHITE CELLS
Authors: David A. Goodwin, I. Ross McDougall, Caroline Chiles, Jack H. Paldi, David A. Krieves, Margaret A. Gainey
Journal: Clinical Nuclear Medicine (1982)

Goodwin, David A.; McDougall, I. Ross; Chiles, Caroline; Paldi, Jack H.; Krieves, David A.; Gainey, Margaret A.Author Information
Selective Reduction — A Perinatal Necessity?
Authors: John C. Hobbins
Journal: New England Journal of Medicine (1988)

Today, it is not unusual for a medical therapy, no matter how exciting its potential, to have a "down side," especially in the early stages of its development and implementation. A perfect example is the occasional occurrence of multiple gestation as a complication of the induction of ovulation in infertile patients.Various studies show an incidence of multiple gestation in induced ovulation ranging from 16 to 39 percent. In one study, multiple gestation occurred in 25 percent of the patients, with five pregnancies involving triplets, two quadruplets, and four quintuplets.1 The mother of multiple fetuses must endure weeks of discomfort . . .
Vitamin K at birth
Authors: A. Zipursky
Journal: BMJ (1996)

Haemorrhagic disease of the newborn can be eradicated without risk of leukaemia or cancer

That all newborn infants are deficient in vitamin K is apparent from their low plasma concentrations of vitamin K and a deficiency of the vitamin K dependent coagulation factors II, VII, IX, and X. This deficiency results in (early) haemorrhagic disease of the newborn in 0.4%-1.7% of babies in the first week of life.1 Late haemorrhagic disease occurs almost exclusively in breast fed infants, from 2 to 12 weeks of age, who did not receive intramuscular vitamin K at birth. The incidence has been reported to vary from 4.4 to 10.5 per 100 000 births.2

Vitamin K given intramuscularly at a dose of 1.0 mg corrects deficiency, prevents haemorrhagic disease of the newborn, and was standard practice until 1990. But in that year Golding et al reported an increased incidence of leukaemia and cancer in children who had received vitamin K intramuscularly at birth.3 This study, based on observations from the Oxford Survey of Childhood Cancers, was followed by a case-control study at two hospitals in Bristol, showing that the incidence of cancer in children who had received vitamin K at birth was twice that of children who had received either no vitamin K or an oral dose only.4

Golding et al's conclusions were supported by observations of the potential carcinogenicity of vitamin K. Israels et al reported that the addition of vitamin K to lymphocyte suspensions increased the rate of sister chromatic exchange,5 which correlates with a …