tbuckley/cabot-search huggingface dataset:
Targeted Gene-and-host Progenitor Cell Therapy for Nonunion Bone Fracture Repair
Authors: Nadav Kimelman-Bleich, Gadi Pelled, Yoram Zilberman, Ilan Kallai, Olga Mizrahi, Wafa Tawackoli, Zulma Gazit, Dan Gazit
Journal: Molecular Therapy (2010)

Nonunion fractures present a challenge to orthopedics with no optimal solution. In-vivo DNA electroporation is a gene-delivery technique that can potentially accelerate regenerative processes. We hypothesized that in vivo electroporation of an osteogenic gene in a nonunion radius bone defect site would induce fracture repair. Nonunion fracture was created in the radii of C3H/HeN mice, into which a collagen sponge was placed. To allow for recruitment of host progenitor cells (HPCs) into the implanted sponge, the mice were housed for 10 days before electroporation. Mice were electroporated with either bone morphogenetic protein 9 (BMP-9) plasmid, Luciferase plasmid or injected with BMP-9 plasmid but not electroporated. In vivo bioluminescent imaging indicated that gene expression was localized to the defect site. Microcomputed tomography (µCT) and histological analysis of murine radii electroporated with BMP-9 demonstrated bone formation bridging the bone gap, whereas in the control groups the defect remained unbridged. Population of the implanted collagen sponge by HPCs transfected with the injected plasmid following electroporation was noted. Our data indicate that regeneration of nonunion bone defect can be attained by performing in vivo electroporation with an osteogenic gene combined with recruitment of HPCs. This gene therapy approach may pave the way for regeneration of other skeletal tissues. Nonunion fractures present a challenge to orthopedics with no optimal solution. In-vivo DNA electroporation is a gene-delivery technique that can potentially accelerate regenerative processes. We hypothesized that in vivo electroporation of an osteogenic gene in a nonunion radius bone defect site would induce fracture repair. Nonunion fracture was created in the radii of C3H/HeN mice, into which a collagen sponge was placed. To allow for recruitment of host progenitor cells (HPCs) into the implanted sponge, the mice were housed for 10 days before electroporation. Mice were electroporated with either bone morphogenetic protein 9 (BMP-9) plasmid, Luciferase plasmid or injected with BMP-9 plasmid but not electroporated. In vivo bioluminescent imaging indicated that gene expression was localized to the defect site. Microcomputed tomography (µCT) and histological analysis of murine radii electroporated with BMP-9 demonstrated bone formation bridging the bone gap, whereas in the control groups the defect remained unbridged. Population of the implanted collagen sponge by HPCs transfected with the injected plasmid following electroporation was noted. Our data indicate that regeneration of nonunion bone defect can be attained by performing in vivo electroporation with an osteogenic gene combined with recruitment of HPCs. This gene therapy approach may pave the way for regeneration of other skeletal tissues.
Thyrotropin-releasing Hormone in the Systemic Circulation of the Neonatal Rat Is Derived from the Pancreas and Other Extraneural Tissues
Authors: Dennis Engler, Maurice F. Scanlon, Ivor M. D. Jackson
Journal: Journal of Clinical Investigation (1981)

Thyrotropin-releasing hormone immunoreactivity (IR-TRH) has been detected in the circulation of the neonatal rat. This immunoreactivity was demonstrated in purified ethanol extracts of plasma, and was indistinguishable from synthetic TRH using radioimmunoassay and chromatographic criteria. To determine the source of the circulating IR-TRH, tissue concentrations of TRH were analyzed during maturation of the rat. These studies revealed that during the first 10 d of life, the pancreas contained the greatest concentration of IR-TRH of any organ (pancreas, 289±35 pg/mg; hypothalamus, 13±3 pg/mg, day 5). Thereafter, pancreatic IR-TRH concentrations declined progressively while hypothalamic concentrations gradually increased (pancreas, 1.2±0.2 pg/mg; hypothalamus, 365±54 pg/mg, adult rat). IR-TRH was also found throughout the gastrointestinal tract but was not detected in the liver, spleen, kidney, or heart. IR-TRH from the pancreas and gastrointestinal tract gave radio-immunoassay binding displacement curves that were parallel to a curve generated with synthetic TRH, and co-migrated with synthetic TRH on Sephadex G-10 and high performance liquid chromatography. In addition, IR-TRH from purified pancreatic extracts was biologically active in that it released thyrotropin and prolactin from rat adenohypophysial cells maintained in monolayer culture. When a total pancreatectomy was performed on the 5th d of life of the rat, mean plasma TRH concentrations were significantly decreased 3 h afterwards (84±9 vs. 63±7 pg/ml, P < 0.05). Neither the TRH concentrations in the brain, hypothalamus, or gastrointestinal tract, nor the pituitary-thyroid axis were affected by the pancreatectomy. However, mean plasma TRH concentrations remained unaltered 3 h after removal of the hypothalamus and extrahypothalamic brain.
Stress and pressure to blame for doctors' poor performance
Authors: Caroline White
Journal: BMJ (2005)

Doctors whose performance gives cause for concern are often highly committed and conscientious people, whose strengths become distorted under pressure and stress, a symposium this week on managing and motivating the medical workforce found.

The findings are based on work with 137 doctors with performance concerns who underwent behavioural assessments, including psychometric testing. Most had been referred to the National Clinical Assessment Service, the NHS body that works with doctors who have got into difficulties.

Jennifer King, chartered psychologist and managing director of Edgecumbe Consulting, which organised the symposium, said the potential behavioural “derailers” …
Human adenovirus-specific T cells modulate HIV-specific T cell responses to an Ad5-vectored HIV-1 vaccine
Authors: Nicole Frahm, Allan C. DeCamp, David P. Friedrich, Donald K. Carter, Olivier D. Defawe, James G. Kublin, Danilo R. Casimiro, Ann Duerr, Michael N. Robertson, Susan P. Buchbinder, Yunda Huang, Gregory A. Spies, Stephen C. De Rosa, M. Juliana McElrath
Journal: Journal of Clinical Investigation (2011)

Recombinant viruses hold promise as vectors for vaccines to prevent infectious diseases with significant global health impacts. One of their major limitations is that preexisting anti-vector neutralizing antibodies can reduce T cell responses to the insert antigens; however, the impact of vector-specific cellular immunity on subsequent insert-specific T cell responses has not been assessed in humans. Here, we have identified and compared adenovirus-specific and HIV-specific T cell responses in subjects participating in two HIV-1 vaccine trials using a vaccine vectored by adenovirus serotype 5 (Ad5). Higher frequencies of pre-immunization adenovirus-specific CD4⁺ T cells were associated with substantially decreased magnitude of HIV-specific CD4⁺ T cell responses and decreased breadth of HIV-specific CD8⁺ T cell responses in vaccine recipients, independent of type-specific preexisting Ad5-specific neutralizing antibody titers. Further, epitopes recognized by adenovirus-specific T cells were commonly conserved across many adenovirus serotypes, suggesting that cross-reactivity of preexisting adenovirus-specific T cells can extend to adenovirus vectors derived from rare serotypes. These findings provide what we believe to be a new understanding of how preexisting viral immunity may impact the efficacy of vaccines under current evaluation for prevention of HIV, tuberculosis, and malaria.
Significant response after treatment with the mTOR inhibitor sirolimus in combination with carboplatin and paclitaxel in metastatic melanoma patients
Authors: Friedegund Meier, Emmanuella Guenova, Stephan Clasen, Thomas Eigentler, Andrea Forschner, Ulrike Leiter, Christina Zielinski, Björn Knaudt, Claus Garbe, Mark Berneburg
Journal: Journal of the American Academy of Dermatology (2009)
Increased gall bladder volume in primary sclerosing cholangitis.
Authors: P C van de Meeberg, P Portincasa, F H Wolfhagen, K J van Erpecum, G P VanBerge-Henegouwen
Journal: Gut (1996)

BACKGROUND: The diagnosis of primary sclerosing cholangitis (PSC) requires invasive procedures such as liver biopsy and endoscopic retrograde cholangiography (ERC). Sonographic measurement of fasting gall bladder volume, which has been reported to be enlarged in PSC, could serve as a non-invasive screening test. METHODS: Fasting gall bladder volume was studied in patients with PSC (n = 24), primary biliary cirrhosis (PBC, n = 13), liver cirrhosis due to other causes (n = 18), ulcerative colitis (n = 15), and healthy controls (n = 23). Meal induced gall bladder emptying was studied in patients with PSC, patients with PBC, and healthy controls. RESULTS: In patients with PSC gall bladder volume was greatly enlarged (72.9 (SEM 3.7) ml) compared with healthy controls (25.4 (1.7) ml, and patients with PBC (30.9 (2.7) ml), liver cirrhosis (31.3 (4.0) ml) or ulcerative colitis (25.8 (2.0) ml) (p &lt; 0.0005 v all). In four patients with PSC the gall bladder wall was irregularly thickened (&gt; 4 mm) as previously described in PSC. Postprandial residual fractions (% of fasting volume) were comparable between patients with PSC (17.5 (3.7)%) and those with PBC (23.6 (7.1%) and healthy controls (12.7 (2.3)%) Although gall bladder emptying seems normal, increased biliary pressure in patients with PSC cannot be excluded. CONCLUSION: Apart from wall thickening, patients with PSC often present with enlargement of the gall bladder. Sonographic determination of fasting gall bladder volume may be a useful, non-invasive, and easy to perform tool in the evaluation of patients suspected of having PSC.
A comparison of PUVA-etretinate and PUVA-placebo for palmoplantar pustular psoriasis
Authors: C.M. LAWRENCE, JANET MARKS, S. PARKER, SAM SHUSTER
Journal: British Journal of Dermatology (1984)

Journal Article A comparison of PUVA‐etretinate and PUVA‐placebo for palmoplantar pustular psoriasis Get access C.M. LAWRENCE, C.M. LAWRENCE University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NEI4LP Dr C.M. Lawrence, University Department of Dermatology, Royal Victorial Infirmary, Newcastle upon Tyne NE1 4LP. Search for other works by this author on: Oxford Academic Google Scholar JANET MARKS, JANET MARKS University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NEI4LP Search for other works by this author on: Oxford Academic Google Scholar S. PARKER, S. PARKER University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NEI4LP Search for other works by this author on: Oxford Academic Google Scholar SAM SHUSTER SAM SHUSTER University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NEI4LP Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 110, Issue 2, 1 February 1984, Pages 221–226, https://doi.org/10.1111/j.1365-2133.1984.tb07471.x Published: 01 February 1984 Article history Accepted: 25 July 1983 Published: 01 February 1984
Nanoscale markers of esophageal field carcinogenesis: potential implications for esophageal cancer screening
Authors: Vani Konda, Lusik Cherkezyan, Hariharan Subramanian, Kirsten Wroblewski, Dhwanil Damania, Valentin Becker, Mariano Gonzalez, Ann Koons, Michael Goldberg, Mark Ferguson, Irving Waxman, Hermant Roy, Vadim Backman
Journal: Endoscopy (2013)

Esophageal adenocarcinoma (EAC) has a dismal prognosis unless treated early or prevented at the precursor stage of Barrett's esophagus-associated dysplasia. However, some patients with cancer or dysplastic Barrett's esophagus (DBE) may not be captured by current screening and surveillance programs. Additional screening techniques are needed to determine who would benefit from endoscopic screening or surveillance. Partial wave spectroscopy (PWS) microscopy (also known as nanocytology) measures the disorder strength (Ld ), a statistic that characterizes the spatial distribution of the intracellular mass at the nanoscale level and thus provides insights into the cell nanoscale architecture beyond that which is revealed by conventional microscopy. The aim of the present study was to compare the disorder strength measured by PWS in normal squamous epithelium in the proximal esophagus to determine whether nanoscale architectural differences are detectable in the field area of EAC and Barrett's esophagus.During endoscopy, proximal esophageal squamous cells were obtained by brushings and were fixed in alcohol and stained with standard hematoxylin and Cyto-Stain. The disorder strength of these sampled squamous cells was determined by PWS.A total of 75 patient samples were analyzed, 15 of which were pathologically confirmed as EAC, 13 were DBE, and 15 were non-dysplastic Barrett's esophagus; 32 of the patients, most of whom had reflux symptoms, acted as controls. The mean disorder strength per patient in cytologically normal squamous cells in the proximal esophagus of patients with EAC was 1.79-times higher than that of controls (P<0.01). Patients with DBE also had a disorder strength 1.63-times higher than controls (P<0.01).Intracellular nanoarchitectural changes were found in the proximal squamous epithelium in patients harboring distal EAC and DBE using PWS. Advances in this technology and the biological phenomenon of the field effect of carcinogenesis revealed in this study may lead to a useful tool in non-invasive screening practices in DBE and EAC.
NINETEEN YEARS' EXPERIENCE WITH CREOSOTE IN TUBERCULOSIS.
Authors: JAMES A. BURROUGHS
Journal: JAMA (1902)

The general who has a difficult battle in contemplation not only surveys the ground and counts his men, but selects his best gun and places it at advantageous points, where it will not only offer the greatest protection to his men, but do its most effectual carnage to the enemy. Other things being equal, success or failure in the treatment of pulmonary tuberculosis depends largely upon a judicious selection and proper administration of creosote. Being located as I am, at a point where a very large number of tubercular patients are directed by the best physicians of the country, I have a good opportunity to obtain a fairly correct opinion of the profession's confidence in creosote. My records for the past nineteen years, of 2183 cases of tuberculosis, scattered from all points of the United States and the provinces of Canada, show that thirteen out of every fifteen patients were
Successful Replacement of the Entire Ascending Aorta and Aortic Valve
Authors: Myron W. Wheat, James R. Wilson, Thomas D. Bartley
Journal: JAMA (1964)

The first successful replacement of the entire ascending aorta from the aortic annulus to the innominate artery, with reimplantation of the coronary ostia and replacement of the aortic valve was performed on a 57-year-old white male. The patient's lesion was a luetic and arteriosclerotic aneurysm of the ascending aorta plus aortic valvular insufficiency. The ascending aorta was replaced with a woven Teflon graft and the aortic valve with a Starr-Edwards prosthesis using extracorporeal support and cold cardiac arrest. The coronary ostia were attached to the Teflon tubular prosthesis. The patient is well without evidence of thrombosis or embolization 13 months later.
Hemoglobin Synthesis and Thalassemia
Authors: Sherman M. Weissman
Journal: JAMA (1967)

The thalassemia syndromes are a group of congenital disorders which produce minimal to moderate anemia in the heterozygote and profound anemia in the homozygote. Thalassemia is widespread in several population groups. It has attracted the attention of many clinical investigators and molecular biologists because of its potential for the understanding of a variety of congenital diseases as well as basic biologic processes. Recent research has established that thalassemia is caused by a failure to produce normal amounts of one of the peptide chains of hemoglobin. The defect occurs even though the peptide produced appears to have a normal structure. This is of interest since some other hereditary disorders due to deficient function of a protein may also be caused by underproduction rather than structural alterations of the enzyme and thalassemia may serve as a prototype for these disorders. While there has been a rapid increase in knowledge of the mechanism
148 LOCALLY ACQUIRED HEPATITIS E. GEOGRAPHICAL CLUSTERING AND ENVIRONMENTAL FACTORS: A NESTED CASE CONTROL STUDY
Authors: R.G. Madden, J.G. Hunter, A.M. Stone, C. Thornton, M. Barlow, J. Lewis, R. Bendall, N. Lin, W. Henley, H.R. Dalton
Journal: Journal of Hepatology (2012)
Severe anaemia and subcapital femur fracture in a patient with Left Ventricular Assist Device Heart Mate II: the cardiologist's management of this rare patient
Authors: Bill D. Gogas, John T. Parissis, Gerasimos S. Filippatos, Efstathios K. Iliodromitis, Konstantinos C. Soultanis, Georgia G. Kostopanagiotou, Stergios P. Theodoropoulos, Dimitrios T. Kremastinos, Magdi H. Yacoub
Journal: European Journal of Heart Failure (2009)
TCT-388 Multi-slice Computer Tomography Analysis of Percutaneous Ventricular Restoration (PVR) using the Parachute Device in Patients with Heart Failure Post Anterior Wall Myocardial Infarction: First-In-Man Experience
Authors: Hiram Bezerra, Sinisa Gradinac, Ernest Mazzaferri, Horst Sievert, Igor Gregoric, Charles Davidson, Peter Berger, Albrecht Elsässer, Ron Waksman, Frank Smart, William Albernathy, William Abraham, Marco Costa
Journal: Journal of the American College of Cardiology (2012)
Metabolic acidosis and fatal myocardial failure after propofol infusion in children: five case reports.
Authors: T. J. Parke, J. E. Stevens, A. S. Rice, C. L. Greenaway, R. J. Bray, P. J. Smith, C. S. Waldmann, C. Verghese
Journal: BMJ (1992)

OBJECTIVE--To examine the possible contribution of sedation with propofol in the deaths of children who were intubated and required intensive care. DESIGN--Case note review. SETTING--Three intensive care units. SUBJECTS--Five children with upper respiratory tract infections aged between 4 weeks and 6 years. RESULTS--Four patients had laryngotracheo-bronchitis and one had bronchiolitis. All were sedated with propofol. The clinical course in all five cases was remarkably similar: an increasing metabolic acidosis was associated with brady-arrhythmia and progressive myocardial failure, which did not respond to resuscitative measures. All children developed lipaemic serum after starting propofol. These features are not usually associated with respiratory tract infections. No evidence was found of viral myocarditis, which was considered as a possible cause of death. CONCLUSION--Although the exact cause of death in these children could not be defined, propofol may have been a contributing factor.
Possible Hepatitis From Diaphragm Fitting
Authors: Louis C. Wislocki
Journal: JAMA (1984)

To the Editor.—  There has been increasing concern about the iatrogenic causes of illness. One of those frequently cited is the spread of hepatitis B by medical practice. This concern has recently become more acute because of the worry that acquired immunodeficiency syndrome (AIDS) on occasion may be similarly disseminated. It has come to my attention that a common medical procedure that may pose a risk for the transmission of disease and specifically of hepatitis B is the use of reusable fitting diaphragms and rings used in the fitting of diaphragms for contraception. It is well recognized that hepatitis B virus may be present in menstrual blood, vaginal secretions, and seminal fluid, and sexual contact may well be a mode of spread of the disease. 1   Instructions by the manufacturer of a major brand of fitting rings and diaphragms call for washing the used rings in soap and water and
Characteristics of Membrane-Bound and Free Hepatic Ribosomes from Insulin-Deficient Rats I. ACUTE EXPERIMENTAL DIABETES MELLITUS
Authors: Daniel T. Peterson, Frank P. Alford, Eve P. Reaven, Irene Ueyama, Gerald M. Reaven
Journal: Journal of Clinical Investigation (1973)

Membrane-bound and free ribosomes were prepared by discontinuous density gradient centrifugation from livers of rats 2-3 days after receiving alloxan (75 mg/kg) or streptozotocin (100 mg/kg). Hepatocytes from these animals were also examined by electron microscopy and subjected to quantitative morphometric analysis. The results indicated that the two populations of hepatic ribosomes respond differently to acute insulin deficiency. There was an overall reduction (P < 0.001) in total number of bound ribosomes per volume cytoplasm: the remaining bound ribosomes underwent a shift to smaller-sized ribosomal messenger RNA (mRNA) aggregates (P < 0.02); and the proteinsynthetic activity of these bound ribosomes was less than normal (P < 0.02) when protein synthesis was directed by endogenous mRNA. However, there was no difference between bound ribosomes from livers of normal and diabetic rats when protein synthesis was directed by polyuridylic acid. In contrast, free ribosomes were unchanged in number and degree of ribosomal mRNA aggregation, but displayed a significantly increased rate of in vitro protein synthesis (P < 0.01) as compared to normal controls. This increased protein-synthetic activity occurred when amino acid incorporation was directed by endogenous mRNA or polyuridylic acid. These changes in structure and function of bound and free hepatic ribosomes were prevented by the concomitant administration of insulin. The decrease in protein-synthetic activity of bound hepatic ribosomes from acutely diabetic rats seems to be secondary to marked disruption and disaggregation of the rough endoplasmic reticulum (RER) with production of smaller ribosomal mRNA aggregates which incorporate less amino acids into protein. Increased protein synthetic activity of free ribosome appears to be related to the ability of these ribosomes to copy mRNA more efficiently.