tbuckley/cabot-search huggingface dataset:
Salmonella typhimurium strain SL7207 induces apoptosis and inhibits the growth of HepG2 hepatoma cells in vitro and in vivo
Authors: Baowei Li, Hongwei He, Shenghua Zhang, Wuli Zhao, Naren Li, Rongguang Shao
Journal: Acta Pharmaceutica Sinica B (2012)

Salmonella typhimurium is probably most extensively studied tumor-targeting bacteria and SL7207 is one of its attenuated strains. SL7207 was first made for bacterial vaccine development and its therapeutic efficacy and safety for hepatocellular carcinoma has not been characterized. In this study, the inhibitory ability of SL7207-lux on human hepatoma HepG2 cells was tested in vitro and in vivo. A bacterial luminescent gene cluster (lux CDABE) was transfected into SL7207 to better monitor the invasion of the bacteria. The results show that SL7207-lux can rapidly enter HepG2 cells and localize in the cytoplasm. This invasion represses cell proliferation and induces apoptosis. In vivo real-time invasion studies showed that the bacteria gradually accumulate in the tumor. This enrichment was confirmed by anatomic observation at 5 days after inoculation. About 40% of tumor growth was inhibited by SL7207-lux at 34 days post-treatment without significant loss of body weight. The area of necrosis of tumor tissue was clearly increased in the treated group. Bacterial quantification showed that the number of colony-forming units per gram of bacteria within tumor tissue was approximately 1000-fold higher than that of liver and spleen. These data suggest that attenuated S. typhimurium strain SL7207 has potential for the treatment of cancers.
Lies and Rude Fools
Authors: Robert G. Westphal
Journal: JAMA (1983)

Children are an incredible race, resilient yet sensitive beyond our own capacity to believe. They have not yet learned to be fools, they are purely simple; they have not yet learned to be rude, they are only honest. But they know the importance of a lie. My patient had two sons, ages 10 and 12, and they had not been to visit their father in the hospital since his urgent, middle-of-the-night admission three days before. The grandparents and my patient's new wife (who was not the boys' mother) were upset by their own grief and uncertain whether the effect of seeing their dying father in such a severe state of illness and confusion would be harmful to the children. I suggested that a brief dose of reality would be much better than the many fantasies and imagined horrors that might be in their young minds. It required a trip of
Homocysteine-induced modulation of tissue plasminogen activator binding to its endothelial cell membrane receptor.
Authors: K A Hajjar
Journal: Journal of Clinical Investigation (1993)

Endothelial cells impart thromboresistance to the blood vessel wall. As modulators of fibrinolytic activity, these cells synthesize and secrete tissue plasminogen activator (t-PA) as well as its physiologic inhibitor, plasminogen activator inhibitor-1. In addition, endothelial cells support membrane-associated assembly of plasminogen and tissue plasminogen activator. Recently, an M(r) approximately 40,000 protein expressed on endothelial cells has been shown to interact noncompetitively through disparate mechanisms with both t-PA and plasminogen, suggesting trimolecular assembly of enzyme, substrate, and receptor (Hajjar, K. A. 1991. J. Biol. Chem. 266:21962-21970). In the present study, treatment of cultured endothelial cells with DL-homocysteine was specifically associated with a selective reduction in cellular binding sites for t-PA. This 65% decrease in binding was associated with a 60% decrease in cell-associated t-PA activity. No change in affinity for t-PA or plasminogen or in the maximal number of binding sites for plasminogen was observed. Matrix-associated t-PA binding sites were not affected. These data suggest a new mechanism whereby homocysteine may perturb endothelial cell function, thus promoting a prothrombotic state at the surface of the blood vessel wall.
One-Stage Replantation of Both Lungs in the Dog
Authors: Fikri Alican
Journal: JAMA (1971)

In clinical lung allotransplantation, the recipient's remaining diseased lung has caused severe ventilation perfusion imbalance in the graft. We have performed one-stage bilateral lung replantation on 26 dogs as a prototype for possible future solution of this physiologic problem. Pulmonary edema was the main cause of death. Ten dogs lived more than 1 month after operation; seven are still alive and vigorous up to 6 1/2 months. X-ray films of the chest, pulmonary arterial pressures, angiograms, and blood gas levels are normal. Conclusions are that (1) pulmonary edema is proportional in severity to the degree of anoxic damage to the graft, and is potentially reversible; (2) one-stage total pulmonary denervation is readily tolerated by the dog; and (3) simultaneous bilateral lung replantation with long-term survival and nearly normal dynamics of ventilation and pulmonary circulation is feasible.
Stereotaxic Hypophyseal Cryosurgery in Acromegaly and Other Disorders
Authors: Alfred M. Dashe
Journal: JAMA (1966)

Stereotaxic cryoablation of the sellar contents has been attempted in eight patients with pituitary tumors and in one patient with Cushing's syndrome due to adrenal hyperplasia. All of six patients with acromegaly were greatly improved. Growth hormone assays confirmed the clinical data. Complications of rhinorrhea and diabetes insipidus occurred in one patient. Two patients with pituitary tumors—are with a recurrent chromophobe adenoma and the other with a chromophobe tumor associated with hyperpigmentation following adrenalectomy—had clinical remissions with no loss of pituitary function. The patient with Cushing's syndrome without evidence of pituitary tumor had no beneficial effect from the procedure and required bilateral adrenalectomy at a later date. Stereotaxic cryoablation appears to be a useful procedure in carefully selected cases of pituitary neoplasm.
Direct Comparison of Neck Pinhole Dual-Tracer and Dual-Phase MIBI Accuracies With and Without SPECT/CT for Parathyroid Adenoma Detection and Localization
Authors: Sherif I. Heiba, Manli Jiang, Javier Rivera, Eric Genden, William Inabnet, Josef Machac, Lale Kostakoglu
Journal: Clinical Nuclear Medicine (2015)

There is uncertainty about accuracies of dual-phase (DP) and dual-tracer (DT) parathyroid scintigraphy with the newly added SPECT/CT. Although SPECT/CT was shown to be helpful in parathyroid adenoma (PA) localization, it may not have optimal resolution as pinhole. This study directly compared diagnostic accuracies and confidences of various imaging protocols on same patients.One hundred fifty-five patients with pathologically confirmed diagnosis were included. Pinhole DP, pinhole DT, pinhole DP SPECT/CT, pinhole DT SPECT/CT, and SPECT/CT with only pinhole-delayed MIBI (D) were reviewed for accuracies and certainties of PA diagnosis/localization. Parathyroid adenomas were classified as clearly or unclearly distinguishable from thyroid. Furthermore, the contribution of pinhole DP to pinhole DT SPECT/CT was assessed.Of 153 PAs, the correct diagnosis/localization was significantly higher by pinhole DT SPECT/CT than pinhole DP SPECT/CT, SPECT/CT D, pinhole DT alone, and DP alone. Parathyroid adenomas were clearly more distinguished from thyroid in pinhole DT than DP with/without SPECT/CT. Consequently, PA diagnosis certainty was higher in pinhole DT than DP, whereas PA localization certainty was higher in both with SPECT/CT. In pinhole DT SPECT/CT, the pinhole DP addition confirmed diagnosis/localization of only 24 uncertain PAs.In this large patient group, the accuracy and certainty of PA diagnosis/localization were higher in pinhole DT SPECT/CT than all other parathyroid scintigraphy protocols. Pinhole DT better identified PA than pinhole DP, whereas SPECT/CT improved PA localization in both protocols. Pinhole DP showed limited contribution and thus should be only considered when PA diagnosis/localization is uncertain by pinhole DT SPECT/CT.
Roentgenographic Evaluation of Umbilical Artery and Vein Catheters
Authors: Stuart B. Paster
Journal: JAMA (1975)

THE INCREASED use of umbilical artery and vein catheters in the newborn nursery by neonatologists and pediatricians has assumed an even greater importance since the introduction of umbilical-vein exchange transfusion by Diamond<sup>1</sup>and the measurement of blood gases by James.<sup>2</sup>Use of this method has now been extended to include the infusion of various solutions and drugs through the catheter, as well as measurement of various blood chemistry levels. The radiologist plays a key role in evaluating the exact location of the catheter and its tip.<sup>3-6</sup>He must be aware of the normal and abnormal locations as well as the inherent complications associated with an abnormal location. <h3>Normal Umbilical Circulation</h3> Material and methods for catheter insertion have been described by previous authors and are beyond the scope of this article.<sup>7</sup>The knowledge of placement and the location of the catheter is based on an understanding of
Early Percutaneous Tracheotomy Versus Prolonged Intubation of Mechanically Ventilated Patients After Cardiac Surgery
Authors: Jean-Louis Trouillet, Charles-Edouard Luyt, Marguerite Guiguet, Alexandre Ouattara, Elisabeth Vaissier, Ralouka Makri, Ania Nieszkowska, Pascal Leprince, Alain Pavie, Jean Chastre, Alain Combes
Journal: Annals of Internal Medicine (2011)

Background: Whether early percutaneous tracheotomy in patients who require prolonged mechanical ventilation can shorten mechanical ventilation duration and lower mortality remains controversial. Objective: To compare the outcomes of severely ill patients who require prolonged mechanical ventilation randomly assigned to early percutaneous tracheotomy or prolonged intubation. Design: Prospective, randomized, controlled, single-center trial (ClinicalTrials.gov registration number: NCT00347321). Setting: Academic center. Patients: 216 adults requiring mechanical ventilation 4 or more days after cardiac surgery. Intervention: Immediate early percutaneous tracheotomy or prolonged intubation with tracheotomy 15 days after randomization. Measurements: The primary end point was the number of ventilator-free days during the first 60 days after randomization. Secondary outcomes included 28-, 60-, or 90-day mortality rates; durations of mechanical ventilation, intensive care unit stay, and hospitalization; sedative, analgesic, and neuroleptic use; ventilator-associated pneumonia rate; unscheduled extubations; comfort and ease of care; and long-term health-related quality of life (HRQoL) and psychosocial evaluations. Results: There was no difference in ventilator-free days during the first 60 days after randomization between early percutaneous tracheotomy and prolonged intubation groups (mean, 30.4 days [SD, 22.4] vs. 28.3 days [SD, 23.7], respectively; absolute difference, 2.1 days [95% CI, −4.1 to 8.3 days]) nor in 28-, 60-, or 90-day mortality rates (16% vs. 21%, 26% vs. 28%, and 30% vs. 30%, respectively). The durations of mechanical ventilation and hospitalization, as well as frequencies of ventilator-associated pneumonia and other severe infections, were also similar. However, early percutaneous tracheotomy was associated with less intravenous sedation; less time of heavy sedation; less haloperidol use for agitation, delirium, or both; fewer unscheduled extubations; better comfort and ease of care; and earlier resumption of oral nutrition. After a median follow-up of 873 days, between-group survival, psychosocial evaluations, and HRQoL were similar. Limitation: The prolonged intubation group had more ventilator-free days during days 1 to 60 than what was hypothesized (mean, 23.0 days [SD, 17.0]). Conclusion: Early tracheotomy provided no benefit in terms of mechanical ventilation and length of hospital stay, rates of mortality or infectious complications, and long-term HRQoL for patients who require prolonged mechanical ventilation after cardiac surgery. However, the well-tolerated procedure was associated with less sedation, better comfort, and earlier resumption of autonomy. Primary Funding Source: French Ministry of Health.
Lead-Contaminated Health Food
Authors: William H. Crosby
Journal: JAMA (1977)

A doctor prescribed a dietary supplement prepared from powdered animal bone for a young woman with dysmenorrhea. Severe lead poisoning developed while she was taking the powder, which was shown to be contaminated with lead. The diagnosis eluded more than 20 physicians and was finally made by the patient herself. The Food and Drug Administration, informed of the contamination, declined to take action, stating that a food supplement is neither a food nor a drug and, besides, there are no maximal limits for heavy-metal contamination of foods and drugs. (<i>JAMA</i>237:2627-2629, 1977)
Fetal and infant growth and cardiovascular risk factors in women
Authors: C H D Fall, C Osmond, D J P Barker, P M S Clark, C N Hales, Y Stirling, T W Meade
Journal: BMJ (1995)

To examine whether cardiovascular risk factors in women are related to fetal and infant growth.Follow up study of women born 1923-30 whose birth weights and weights at one year were recorded.Hertfordshire.297 women born and still living in East Hertfordshire.Plasma glucose and insulin concentrations during a standard oral glucose tolerance test; fasting plasma proinsulin and 32-33 split proinsulin concentrations; blood pressure; fasting serum total, low density lipoprotein and high density lipoprotein cholesterol, triglyceride, and apolipoprotein A I and B concentrations; and plasma fibrinogen and factor VII concentrations.Fasting plasma concentrations of glucose, insulin, and 32-33 split proinsulin fell with increasing birth weight (P = 0.04, P = 0.002, and P = 0.0002 respectively, when current body mass index was allowed for). Glucose and insulin concentrations 120 minutes after an oral glucose load showed similar trends (P = 0.03 and P = 0.02). Systolic blood pressure, waist:hip ratio, and serum triglyceride concentrations also fell with increasing birth weight (P = 0.08, P = 0.07, and P = 0.07 respectively), while serum high density lipoprotein cholesterol concentrations rose (P = 0.04). At each birth weight women who currently had a higher body mass index had higher levels of risk factors.In women, as in men, reduced fetal growth leads to insulin resistance and the associated disorders: raised blood pressure and high serum triglyceride and low serum high density lipoprotein cholesterol concentrations. The highest values of these coronary risk factors occur in people who were small at birth and became obese. In contrast with men, low rates of infant growth did not predict levels of risk factors in women.
Repression of class II major histocompatibility complex genes by cyclic AMP is mediated by conserved promoter elements.
Authors: L B Ivashkiv, L H Glimcher
Journal: The Journal of Experimental Medicine (1991)

The induction of cell surface expression of class II major histocompatibility complex (MHC) antigens by interleukin (IL)-4 and interferon (IFN)-gamma is inhibited by elevation of intracellular cyclic (c)AMP, which is caused by immunomodulatory agents such as E series prostaglandins (PGEs). To investigate the mechanism of this downregulation, we have analyzed the consequences of elevating intracellular cAMP on cell surface expression, mRNA levels, and promoter activity of the murine A alpha and E beta class II MHC genes. Elevation of cAMP resulted in a coordinate repression of both basal and inducible A alpha and E beta expression. 151 and 192 base pairs of A alpha and E beta promoter sequence, respectively, were sufficient for conferring repression by cAMP on a reporter gene. A mutational analysis of the A alpha promoter revealed that cAMP downregulation is mediated by the conserved S and X1 DNA elements, which are also necessary for induction by cytokines. Downregulation by cAMP was not dependent on an intact X2 site, which is identical in sequence to the CRE element which mediates the positive regulation of several genes by cAMP. These results identify the DNA elements which mediate repression of class II MHC genes by cAMP and show that the same DNA sequences can mediate both positive and negative regulation of class II MHC expression.
Decreasing Rate and Extent of Lymph Node Staging in Patients Undergoing Radical Prostatectomy May Undermine the Rate of Diagnosis of Lymph Node Metastases in Prostate Cancer
Authors: Firas Abdollah, Maxine Sun, Rodolphe Thuret, Lars Budäus, Claudio Jeldres, Markus Graefen, Alberto Briganti, Paul Perrotte, Patrizio Rigatti, Francesco Montorsi, Pierre I. Karakiewicz
Journal: European Urology (2010)
Selectivity Index as a Guide to Treatment in Heavy Proteinuria.
Authors: William E. Miller
Journal: Annals of Internal Medicine (1968)

s1 May 1968Selectivity Index as a Guide to Treatment in Heavy Proteinuria.William E. Miller, M.D., Sharad D. Deodhar, M.D., Ray W. Gifford Jr., M.D., F.A.C.P., David C. Humphrey, M.D., F.A.C.P., Donald G. Vidt, M.D.William E. Miller, M.D.Search for more papers by this author, Sharad D. Deodhar, M.D.Search for more papers by this author, Ray W. Gifford Jr., M.D., F.A.C.P.Search for more papers by this author, David C. Humphrey, M.D., F.A.C.P.Search for more papers by this author, Donald G. Vidt, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1182_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptCameron and blandford recently proposed a simplified method for assessing the selectivity of proteinuria in patients with nephrotic syndrome. The ratio of the clearance immunoglobulin (IgG) to the clearance of transferrin correlated well with response to immunosuppressive therapy.The selectivity indexes of 29 patients (25 adults, 4 children) with heavy proteinuria (> 2.0 g/day) were determined before the beginning of immuno-suppressive therapy. Histologic correlation from renal biopsy specimens was available in all cases.Sixteen patients had selectivity indexes of 0.2 or less. Eleven of these patients responded favorably to immunosuppressive treatment, three with a complete remission. Selectivity indexes of greater... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cleveland, Ohio PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1968Volume 68, Issue 5Page: 1182-1182KeywordsBiopsyChildrenImmunosuppressivesProteinuria Issue Published: 1 May 1968 PDF downloadLoading ...
Analysis of Surgical Salvage After Failure of Primary Therapy in Rectal Cancer: Results From Intergroup Study 0114
Authors: J.E. Tepper, M. O’Connell, D. Hollis, D. Niedzwiecki, E. Cooke, R.J. Mayer
Journal: Journal of Clinical Oncology (2003)

Purpose: Intergroup Study 0114 was designed to study the effect of various chemotherapy regimens delivered after potentially curative surgical resection of T3, T4, and/or node-positive rectal cancer. A subset analysis was undertaken to investigate the prevalence and influence of salvage therapy among patients with recurrent disease. Patients and Methods: Adjuvant therapy consisted of two cycles of fluorouracil (FU)-based chemotherapy followed by pelvic irradiation with chemotherapy and two more cycles of chemotherapy after radiation therapy. A total of 1,792 patients were entered onto the study and 1,696 were assessable. After a median of 8.9 years of follow-up, 715 patients (42%) had disease recurrence, and an additional 10% died without evidence of disease. Five hundred patients with follow-up information available had a single organ or single site of first recurrence (73.5% of all recurrences). Results: A total of 171 patients (34% of those with a single organ or single site of recurrence) had a potentially curative resection of the metastatic or locally recurrent disease. Single-site first recurrences in the liver, lung, or pelvis occurred in 448 patients (90% of the single-site recurrences), with 159 (35%) of these undergoing surgical resection for attempted cure. Overall survival differed significantly between the resected and nonresected groups (P &lt; .0001), with overall 5-year probabilities of .27 and .06, respectively. Controlling for worst performance status at the time of recurrence does not alter this relationship. Patients who underwent salvage surgery had significantly increased survival (P &lt; .001) for each site. Conclusion: Attempted surgical salvage of rectal cancer recurrence is performed commonly in the United States. The chance of a long-term cure with such intervention is approximately 27%.
The Cysteine Protease Activity of the Major Dust Mite Allergen Der P 1 Selectively Enhances the Immunoglobulin E Antibody Response
Authors: Lucy Gough, Oliver Schulz, Herb F. Sewell, Farouk Shakib
Journal: The Journal of Experimental Medicine (1999)

The house dust mite Dermatophagoides pteronyssinus allergen Der p 1 is the most immunodominant allergen involved in the expression of dust mite–specific immunoglobulin (Ig)E–mediated hypersensitivity. The reason for this potent IgE-eliciting property of Der p 1 remains unknown, but there is mounting in vitro evidence linking the allergenicity of Der p 1 to its cysteine protease activity. Here we demonstrate for the first time that immunization of mice with proteolytically active Der p 1 results in a significant enhancement in total IgE and Der p 1–specific IgE synthesis compared with animals immunized with Der p 1 that was irreversibly blocked with the cysteine protease inhibitor E-64. We conclude that the proteolytic activity of Der p 1 is a major contributor to its allergenicity.
Absence of LTB4/BLT1 axis facilitates generation of mouse GM-CSF–induced long-lasting antitumor immunologic memory by enhancing innate and adaptive immune systems
Authors: Yosuke Yokota, Hiroyuki Inoue, Yumiko Matsumura, Haruka Nabeta, Megumi Narusawa, Ayumi Watanabe, Chika Sakamoto, Yasuki Hijikata, Mutsunori Iga-Murahashi, Koichi Takayama, Fumiyuki Sasaki, Yoichi Nakanishi, Takehiko Yokomizo, Kenzaburo Tani
Journal: Blood (2012)
Antithetic regulation by β-adrenergic receptors of Gq receptor signaling via phospholipase C underlies the airway β-agonist paradox
Authors: Dennis W. McGraw, Khalid F. Almoosa, Richard J. Paul, Brian K. Kobilka, Stephen B. Liggett
Journal: Journal of Clinical Investigation (2003)

β-adrenergic receptors (βARs) relax airway smooth muscle and bronchodilate, but chronic β-agonist treatment in asthma causes increased sensitivity to airway constriction (hyperreactivity) and is associated with exacerbations. This paradox was explored using mice with ablated βAR genes (βAR–/–) and transgenic mice overexpressing airway smooth muscle β2AR (β2AR-OE) representing two extremes: absence and persistent activity of airway βAR. Unexpectedly, βAR–/– mice, lacking these bronchodilating receptors, had markedly decreased bronchoconstrictive responses to methacholine and other Gq-coupled receptor agonists. In contrast, β2AR-OE mice had enhanced constrictive responses. Contraction to permeabilization with β-escin was unaltered by gene ablation or overexpression. Inositol phosphate accumulation by Gq-coupled M3-muscarinic, thromboxane-A2, and 5-HT2 receptors was desensitized in airway smooth muscle cells from βAR–/– mice and sensitized in cells from β2AR-OE mice. Thus, βAR antithetically regulates constrictive signals, affecting bronchomotor tone/reactivity by additional means other than direct dilatation. Studies of signaling elements in these pathways revealed the nodal point of this cross talk as phospholipase C-β1, whose expression was altered by βAR in a direction and magnitude consistent with the physiologic and cellular responses. These results establish a mechanism of the β-agonist paradox and identify a potential asthma modifier gene (phospholipase C-β1), which may also be a therapeutic target in asthma when chronic β-agonists are required.