tbuckley/cabot-search huggingface dataset:
Perillyl Alcohol Inhibits a Calcium-Dependent Constitutive Nuclear Factor-κB Pathway
Authors: Craig M. Berchtold, Kai-Shun Chen, Shigeki Miyamoto, Michael N. Gould
Journal: Cancer Research (2005)

Abstract The cell death induced by the monoterpene anticancer agent perillyl alcohol correlates to the increased expression of certain proapoptotic genes known to influence cell survival. Whereas sequence-specific DNA-binding factors dictate the expression patterns of genes through transcriptional regulation, those transcriptional factors influencing constitutive cell survival with perillyl alcohol treatment are not well studied. Here, we investigated whether the monoterpenes can regulate the activity of nuclear factor-κB (NF-κB), a calcium-dependent transcription factor necessary for survival in the WEHI-231 B-lymphoma cells. Unique among the monoterpenes, perillyl alcohol short-term treatment induced a persistent decrease of calcium levels, whereas other various monoterpenes caused transient reductions in calcium levels. Perillyl alcohol treatment also rapidly elicited reductions of NF-κB DNA-binding activity and target gene induction, which was associated with an increase in apoptosis in these B-lymphoma cells. This apoptosis was directly due to NF-κB because its prior activation abolished the cell killing effects of perillyl alcohol treatment. Our findings suggest that perillyl alcohol can inhibit NF-κB function to modulate gene expression patterns and cell survival of certain B-lymphoma cells. The effects of perillyl alcohol were not limited to these B-lymphoma cells but were also observed in MDA-MB 468 cells, an estrogen receptor–negative breast cancer cell line. These results identify a calcium-dependent NF-κB pathway as a molecular target of perillyl alcohol activity in different cancer cell types.
Ventricular Myocyte Caspases Are Directly Responsible for Endotoxin-Induced Cardiac Dysfunction
Authors: Steve Lancel, Olivier Joulin, Raphael Favory, Jean Francois Goossens, Jérome Kluza, Claude Chopin, Pierre Formstecher, Philippe Marchetti, Remi Neviere
Journal: Circulation (2005)

Although most of the deleterious effects of sepsis-induced apoptosis have been attributed to increased lymphocyte cell death, caspase activation may directly alter cell function of different organ systems. We postulated that left ventricular (LV) cardiomyocyte caspase activation is directly involved in sepsis-induced heart contractile dysfunction.LV cardiomyocytes isolated 4 hours after rat treatment with endotoxin injection (10 mg/kg) displayed major reductions in contractile reserve and myofilament response to Ca2+. Concomitantly, endotoxin also induced increases in LV cardiomyocyte caspase-3, -8, and -9-like activities, which were associated with sarcomeric structure destruction and cleavage of components of the cardiac myofilament. Interestingly, zVAD.fmk treatment of septic rat prevented LV cardiomyocyte contractile dysfunction, reductions in myofilament response to calcium, troponin T cleavage, and sarcomere destruction. Serum (10%) of endotoxin-treated rats induced contractile dysfunction, caspase-3-like activity increase, and troponin T cleavage of naive LV cardiomyocytes. The effects of septic serum were prevented in LV cardiomyocytes isolated from zVAD.fmk- or zDEVD.cmk-treated rats or LV cardiomyocytes preincubated with zVAD.fmk or zDEVD.cmk.The results show an important relationship between endotoxin-induced caspase activation and reduced contractile reserve and sarcomere disarray at the level of single LV cardiomyocytes.
Increased factor IX levels in puerperium during administration of diethylstilboestrol.
Authors: D. G. Daniel, A. L. Bloom, J. C. Giddings, H. Campbell, A. C. Turnbull
Journal: BMJ (1968)

Absorption of iron-59 in the form of ferrous sulphate and labelled haemoglobin has been tested in patients having various forms of acute hepatitis.Iron absorption was in the lower range of normal in patients with acute liver disease, except those who had lupoid hepatitis or iron deficiency.Pancreatic extract did not affect the absorption of iron in these patients.Chemical liver damage in rats did not affect iron absorption.
The prevalence of F508 in primary osteoporotic patients
Authors: A. Treszl, K. Németh, I. Kocsis, B. Vásárhelyi, G. Fekete, T. Tulassay, M. Szathmári
Journal: European Respiratory Journal (2005)

tuberculosis (TB) and sarcoidosis.In contrast to our study, they retrospectively analysed 88 patients with biopsy-proven sarcoidosis and 76 patients with culture-positive pulmonary TB.
Antigen detection in primary HIV infection
Authors: M von Sydow, H Gaines, A Sonnerborg, M Forsgren, P O Pehrson, O Strannegard
Journal: BMJ (1988)

Serial blood samples were obtained from 21 homosexuals who had developed symptomatic primary infection with human immunodeficiency virus (HIV) after a median incubation time of 14 days. During the first two weeks after the onset of illness HIV antigen (p24) was detected in the blood by enzyme linked immunosorbent assay (ELISA). During the second and third weeks after the onset of illness p24 antibody was detected by Western blot assay and antigen concentrations rapidly decreased to undetectable values. Dissociation of antigen-antibody complexes showed complexed antigen during the phase of declining concentrations of free antigen. Neither free nor complexed antigen was detected in any serum samples for several months thereafter, which suggested that failure to detect HIV antigen reflected low or absent synthesis of viral protein rather than masking of antigen by antibodies. Reappearance of HIV antigen with a fall in p24 antibody concentration was observed in a few patients six months or more after the onset of disease. The combined use of antigen and antibody assays made it possible to obtain evidence of infection with HIV in all of the 95 serum samples tested, illustrating the usefulness of these assays for diagnosing infection with HIV in its early stages.
NARCOTIC DRUG ADDICTION
Authors: C. C. Wholey
Journal: JAMA (1924)

<h3>To the Editor:</h3> —Many of the statements made by Drs. Sceleth and Kuh in their article inThe Journal, March 1, are at variance with my own observations in drug cases. The assertion is made that "in all instances the narcotic was withdrawn in less than two weeks' time.... There were no acute withdrawal symptoms, drug psychoses, or serious asthenic symptoms.... These patients were no more trouble than any other patients when they actually knew that nothing they could do would produce another dose of morphin." Compared with my own experience, these results are extraordinary. During the last ten years, as part of my psychiatric work, approximately fifteen hundred such cases have come under my personal observation or treatment. These patients were handled chiefly in the psychopathic and medical departments of St. Francis and the Western Pennsylvania hospitals. They came from every walk in life. As to the short withdrawal
An Improved Permeabilization Protocol for the Introduction of Peptides Into Cardiac Myocytes
Authors: John A. Johnson, Mary O. Gray, Joel S. Karliner, Che-Hong Chen, Daria Mochly-Rosen
Journal: Circulation Research (1996)

We have developed an improved, less disruptive procedure for the transient permeabilization of neonatal cardiac myocytes using saponin. The method allows delivery of peptides to a high percentage of cells in culture without effects on long-term cell viability. Permeation was confirmed microscopically by cellular uptake of a fluorescently labeled peptide and biochemically by uptake of 125 I-labeled calmodulin and a 20-kD protein kinase Cε fragment into the cells. The intracellular molar concentration of the introduced peptide was ≈10% of that applied outside. We found no significant effects of permeabilization on spontaneous, phorbol ester–modulated, or norepinephrine-modulated contraction rates. Similarly, the expression of c- fos mRNA (measured 30 minutes after permeabilization) and the incorporation of [ 14 C]phenylalanine following agonist stimulation (measured 3 days after permeabilization) were not altered by saponin permeabilization. Finally, permeabilization of cells in the presence of a protein kinase C pseudosubstrate peptide, but not a control peptide, inhibited phorbol ester–induced [ 14 C]phenylalanine incorporation into proteins by 80%. Our results demonstrate a methodology for the introduction of peptides into neonatal cardiac myocytes that allows study of their actions without substantial compromises in cell integrity.
Who Is the Poor Historian?
Authors: John L. Coulehan
Journal: JAMA (1984)

We cluster in the hall on rounds. A medication nurse pushes her cabinet around us on her way down the hall, while the breakfast lorry closes in from the other direction.  The intern begins his presentation: Mr Blank is a 52-year-old man who presents with abdominal pain... the patient is a  historian.  We learn that this sick person claims to have a number of symptoms and he is apparently taking several medications. The intern adds that the patient's compliance is poor, he doesn't seem to understand his illness, and he is, after all, a poor historian. Having dispensed with the preliminaries, the house officer moves on to reporting the patient's physical findings and the initial laboratory data. At this point he drops all qualifiers: the magnesium level does not seem to be 2.2, it is 2.2.  Once again, we have left the patient and gone on to his biochemistry
Noninvasive Quantification of Regional Myocardial Metabolic Rate of Oxygen by <sup>15</sup> O <sub>2</sub> Inhalation and Positron Emission Tomography
Authors: Yusuke Yamamoto, Ranil de Silva, Christopher G. Rhodes, Hidehiro Iida, Adriaan A. Lammertsma, Terry Jones, Attilio Maseri
Journal: Circulation (1996)

Background The purpose of this study was to validate a novel method for noninvasive quantification of regional myocardial oxygen consumption (MMR o 2 , mL·min −1 ·100 g −1 ) and oxygen extraction fraction (OEF) by use of positron emission tomography (PET) and inhalation of 15 O-labeled molecular oxygen gas ( 15 O 2 ). Methods and Results Twenty-four measurements were performed in eight closed-chest anesthetized greyhounds at baseline and during infusions of adenosine (100 to 200 μg·kg −1 ·min −1 ), isoproterenol (1 to 10 μg/min), and propranolol (5 mg bolus+0.2 to 1 mg/min) with morphine (5 mg slow infusion+0.2 to 0.5 mg/min) to obtain a wide range of oxidative metabolism. The PET imaging protocol consisted of 15 O 2 emission (OEF and MMR o 2 ), transmission, [ 15 O]CO emission (blood pool), and [ 15 O]CO 2 emission (myocardial blood flow: MBF pet , mL·min −1 ·g −1 ) scans. OEF was calculated from the PET data (OEF pet ) by three different analytical techniques: steady-state, 5-minute, and 8-minute autoradiographic analyses. Reference measurements of MBF (MBF ref ) and OEF (OEF ref ) were obtained during 15 O 2 inhalation with radiolabeled microspheres and paired arterial and coronary sinus blood sampling, respectively. MMR o 2 was calculated from the PET (MMR o 2pet ) and the reference (MMR o 2ref ) data as follows: MMR o 2 =OEF×MBF×(O 2 content of arterial blood). OEF measured by the steady-state PET method was well correlated with the reference data over the range 0.16 to 0.73 (OEF pet =1.03 OEF ref −0.01, r =.97), as was MMR o 2 over the range 2.4 to 27.5 mL·min −1 ·100 g −1 (MMR o 2pet =0.98 MMR o 2ref +0.91, r =.94). OEF pet calculated by use of the 5-minute and 8-minute autoradiographic analyses were equally well correlated with the reference measurements ( r =.95 and r =.97, respectively). There were no significant differences between values of MMR o 2pet calculated by use of the steady-state, 5-minute, and 8-minute autoradiographic analyses ( P =NS by ANOVA). Regional values of MBF pet , OEF pet , and MMR o 2pet were homogeneously distributed and similar to the whole-heart values both at baseline and during the various pharmacological interventions. Conclusions Accurate quantification of OEF and MMR o 2 is feasible with 15 O 2 inhalation and PET imaging using both the steady-state and autoradiographic analytical approaches. These studies suggest the applicability of this method for quantitative assessments of regional cardiac oxidative metabolism in clinical studies.
Unusual Features in Fatal Infectious Mononucleosis
Authors: S. Marshall, K. S. Millingen
Journal: BMJ (1952)

HAEMOLYTIC ANAEMIA AND RETICULOSES BJORNSL 1325 tion of red cells as a result of adsorption of antibody, it may be argued that the antibody in these cases is some product of the malignant tissue, or of reaction to this tissue.Alternatively, the abnormal-tissues may destroy excessive numbers of red cells, and thus provoke haemolytic antibody production.Whether this is the first step may depend on the type of reticulosis.Erythrophagocytosis is a usual and pronounced feature of histiocytic medullary reticulosis and an occasional finding in Hodgkin's disease; it occurs rarely if ever in significant degree in lymphosarcoma, while in carcinomatosis the abnormal cells have no phagocytic ability.In the last-named types, therefore, some factor other than phagocytosis must initiate the haemolytic pro- cess.The early appearance of haemolytic signs is also more readily understood on the basis of an antibody mechanism. SummaryFour cases of haemolytic anaemia are described.They were associated with different types of reticulosis.The type of anaemia and possible mechanisms of haemolysis are discussed.I wish to thank the physicians of Guy's Hospital, under whom these patients were admitted, for the use of the case histories.Mr. E. S. Bolton, of Yeovil, and Dr. A. M. Thomas, of Taunton, gave generous help in the follow-up of Case 2.
"This Long Disease, My Life": Alexander Pope and the Sciences
Authors: Lester S. King
Journal: JAMA (1969)

In childhood Alexander Pope contracted what seems to have been tuberculosis of the spine—Pott's disease. He died at the age of 56, of what apparently was congestive failure. Despite his physical disabilities, he produced some magnificent poetry and, as one of the great wits of his era, exerted profound influence on letters during the first half of the 18th century. In addition to his main illness, he suffered a wide variety of complaints and underwent a wide variety of treatments. Nicolson and Rousseau, in this excellent little book, provide a medical history of Pope, drawn from contemporary primary sources as well as sound secondary sources, and also have the benefit of competent medical consultation. The discussions of Pope's ailments not only provide important biographical data but throw much light on the relations between his changing states of health and his poetry. The book really comprises four separate essays. The first
Salt-and-Pepper Retinopathy of Rubella
Authors: Rahul N Khurana, Srinivas R Sadda
Journal: New England Journal of Medicine (2006)

39-year-old woman presented at a clinic for a second opinion regarding a diagnosis of age-related macular degeneration, which had been noted on routine ophthalmologic examination. She reported having no visual problems. Her medical history was notable for congenital hearing loss associated with her mother’s having contracted rubella during her pregnancy. The visual acuity was 20/20 in both eyes. Findings on slit-lamp examination and intraocular pressure were normal. Funduscopic examination revealed granular, pigmentary mottling in the macula and periphery, with punctuate hypopigmentation (arrowheads) and hyperpigmentation (arrows) consistent with the “salt-and-pepper” retinopathy of rubella. The findings on cardiac examination were normal. The classic triad of congenital rubella includes ocular abnormalities, heart disease, and deafness, but myriad other signs have been reported. Congenital rubella produces a classic salt-and-pepper pigmentation of the fundus, as seen in this patient. The nonprogressive retinopathy is generally benign and does not interfere with vision unless choroidal neovascularization develops in the macula. At follow-up four months later, the patient continued to be asymptomatic and no changes were noted
A3.26 Proteasome inhibition with bortezomib in refractory SLE inhibits type I interferon and depletes plasma cells but does not inhibit their regeneration
Authors: Tobias Alexander, Qingyu Cheng, Jens Klotsche, Bimba Hoyer, Adriano Taddeo, Aderajew Waka, Anja A Kühl, Gerd-Rüdiger Burmester, Andreas Radbruch, Falk Hiepe
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The proteasome inhibitor bortezomib, approved for the treatment of multiple myeloma, has been demonstrated to deplete short- and long-lived plasma cells (PCs) and ameliorate nephritis in murine models of systemic lupus erythematosus (SLE). Here, we aimed to analyse the effect of bortezomib in refractory SLE patients. <h3>Methods</h3> In this single-centre cohort study, eight SLE patients with active disease despite immunosuppressive treatment received up to four 21-day cycles of bortezomib 1.3mg/m<sup>2</sup>, on days 1, 4, 8, and 11 by intravenous injection as an "off-label" treatment. Multicolor flow cytometry was performed to analyse peripheral blood B and PC subsets as well as Siglec-1 expression on monocytes. Autoantibody and vaccine titres as well as B cell activating factor (BAFF) levels in serum were analysed with ELISA. <h3>Results</h3> From 2009 until 2012, eight SLE patients received a median of two bortezomib cycles (range one to four). Under proteasome inhibition, disease activity significantly improved with a median SLEDAI reduction from 13 to 4 (p&gt;0.001). Bortezomib treatment had profound effects on antibody titers, with greater reduction in pathogenic (anti-dsDNA-abs. 58.7%) than protective antibody titers (e.g. anti-Tetanus-abs. 29.2%). In addition, total immunoglobulin levels and Siglec-1 expression on monocytes (as surrogate for type I interferon) significantly decreased (p = 0.016), whereas BAFF and complement levels significantly increased. While circulating B-cell numbers remained unaffected, bortezomib treatment resulted in a significant depletion of both HLA-DR<sup>+</sup> short-lived (55.5% reduction, p = 0.024) and HLA-DR- long-lived (53.5% reduction, p = 0.038) peripheral blood PCs. Also IgA secreting PCs were depleted (61.8% reduction). Nevertheless, PCs were rapidly regenerated with a median increase of 268.8% within 10 days from the last bortezomib application. <h3>Conclusion</h3> Proteasome inhibition with bortezomib has beneficial effects on disease manifestations in SLE by PC depletion and inhibition of type I interferon but regeneration of PCs is not prevented. Overall, proteasome inhibition has demonstrated the therapeutic relevance of targeting autoreactive memory plasma cells as such, and it constitutes a new therapeutic option. Nevertheless, fur sustained efficacy, proteasome inhibition needs to be combined with therapeutic approaches targeting B cell activation and differentiation to inhibit PC regeneration.
PERSONALITY IN PARESIS
Authors: MICHAEL OSNATO
Journal: JAMA (1918)

American psychiatrists, led by Meyer, Hoch, Jelliffe, Kirby and others, have revived interest in the study of the development of various mental disorders, particularly dementia praecox, by definitely showing the great part which the personality of the individual plays in the development, progress and nature of a given psychosis. The major part of this work has been done in dementia praecox and manic depressive insanity, and conditions allied to these two abnormal mental reactions. Recently I<sup>1</sup>reported 144 cases of mental disease selected from a great number of cases which were observed at the Vanderbilt Clinic and were studied particularly with the idea of bringing out peculiarities of make-up. The results have confirmed the observations long ago made by the writers mentioned above. Further, however, it seemed interesting to note that in twenty-five cases of undoubted general paresis, those cases which were distinctly psychotic developed in persons with peculiar
Abstract 2455: The fjord region (±)-anti-dibenzo[<i>a,l</i>]pyrene-11,12-dihydrodiol-13,14-epoxides ((±)-anti-DB[<i>a,l</i>]PDE), is a powerful and specific inducer of squamous cell carcinoma in the oral cavity of mice
Authors: Kun-Ming Chen, Joseph B. Guttenplan, Cesar Aliaga, Timothy Cooper, Joseph Deltondo, Wieslawa Kosinska, Arun K. Sharma, Yuan-Wan Sun, Shangmin Zhang, Kun Jiang, Richard Bruggeman, Shantu Amin, Karam El-Bayoumy
Journal: Cancer Research (2010)

Abstract Head and neck squamous cell carcinoma (HNSCC), the sixth most common malignancy, represents a major international public health problem. The vast majority of HNSCC occurs in the oral cavity. Cancer of the mouth strikes about 30,000 Americans each year and less than 50% of patients survive 5 years after diagnosis. Tobacco and alcohol use are considered major causative agents. Current preclinical animal models to study oral carcinogenesis do not accurately mimic the biology of this disease in humans. We have developed a new mouse model by the application of the fjord region diol epoxide, (±)-anti-DB[a,l]PDE, a metabolite of the tobacco constituent dibenzo[a,l]pyrene (DB[a,l]P), to the oral cavity, and we showed for the first time that it is a powerful and specific inducer of oral squamous cell carcinoma (OSCC) in both tongue and oral tissues. Briefly, two groups of B6C3F1 mice (20/group) received doses of (±)-anti-DB[a,l]PDE (6, and 3 nmol) administered into the oral cavity; additional groups received the vehicle or left untreated as controls, 3 time a week for 38 weeks. Mice were sacrificed one year after the first carcinogen administration. The high dose induced 74 % and 100 % OSCC in the tongue and oral tissues, respectively; the corresponding values at the lower dose were 45 % and 89 %. Consistent with the carcinogenicity, we demonstrated powerful mutagenicity in CII gene in big blue mice and the mutation spectra in both tongue and oral tissues revealed similarity in the profiles between DB[a,l]PDE, and that of p53 mutations found in human OSCC. Using immunohistochemistry, we showed that (±)-anti-DB[a,l]PDE resulted in overexpression of p53 protein in malignant tissues compared to normal oral tissues and tongues. Collectively, we developed a non-surgical whole animal model which is the first to demonstrate the remarkable carcinogenicity and specificity of (±)-anti-DB[a,l]PDE in the oral cavity; this model is an appropriate platform for further exploring the genetic and epigenetic alterations that can truly account for the development of OSCC on humans. In addition, this model can be employed to study efficacies of novel cancer chemopreventive agents. Supported by NCI grant no. R01 CA 100924. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2455.