tbuckley/cabot-search huggingface dataset:
Mechanisms of intrathymic tolerance induction to isolated rat hepatocyte allografts
Authors: P Attavar, L Budhai, B Kim, N Roy-Chowdhury, J Roy-Chowdhury, A Davidson
Journal: Hepatology (1997)

Intrathymic injection of alloantigen in young adult rats is capable of mediating long-lived transplantation tolerance. In this study, we use a well-defined model of isolated hepatocyte transplantation to define the mechanisms of intrathymic induced tolerance. The recipient rats are Nagase analbuminemic rats (NAR) that are deficient in albumin, to allow for following transplant acceptance using metabolic and genetic markers. Tolerance to allogeneic hepatocyte transplants could be mediated by intrathymic injection of live allogeneic splenocytes, lethally irradiated splenocytes, or isolated hepatocytes. Intrathymic injection of live allogeneic splenocytes, but not of hepatocytes or irradiated splenocytes, resulted in donor microchimerism in peripheral lymphoid organs, with preferential expansion of CD4-positive T cells in the recipient spleens. Tolerance could be adoptively transferred from tolerant animals to naive recipients, but only from those animals that had been inoculated with intrathymic donor splenocytes. We conclude that donor microchimerism is found after intrathymic inoculation of live splenocytes, but is not required for tolerance induction and that microchimerism is not an absolute requirement for the generation of regulatory cells.
Seasonal and spatial variation of the bacterial mutagenicity of fine organic aerosol in southern california.
Authors: M P Hannigan, G R Cass, A L Lafleur, W F Busby, W G Thilly
Journal: Environmental Health Perspectives (1996)

The bacterial mutagenicity of a set of 1993 urban particulate air pollution samples is examined using the Salmonella typhimurium TM677 forward mutation assay. Amibent fine particulate samples were collected for 24 hr every sixth day throughout 1993 at four urban sites, including Long Beach, central Los Angeles, Azusa, and Rubidoux, California, and at an upwind background site on San Nicolas Island. Long Beach and central Los Angeles are congested urban areas where air quality is dominated by fresh emissions from air pollution sources; Azuasa and Rubidoux are located farther downwind and receive transported air pollutants plus increased quantities of the products of atmospheric chemical reactions. Fine aerosol samples from Long Beach and Los Angeles show a pronounced seasonal variation in bacterial mutagenicity per cubic meter of- ambient air, with maximum in the winter and a minimum in the summer. The down-wind smog receptor site at Rubidoux shows peak mutagenicity (with postmitochondrial supernatant but no peak without postmitochondrial supernatant) during the September-October periods when direct transport from upwind sources can be expected. At most sites the mutagenicity per microgram of organic carbon from the aerosol is not obviously higher during the summer photochemical smog period than during the colder months. Significant spatial variation in bacterial mutagenicity is observed: mutagenicity per cubic meter of ambient air, on average, is more than an order of magnitude lower at San Nicolas Island than within the urban area. The highest mutagenicity values per microgram of organics supplied to the assay are found at the most congested urban sites at central Los Angeles and Long Beach. The highest annual average values of mutagenicity per cubic meter of air sampled occur at central Los Angeles. These findings stress the importance of proximity to sources of direct emissions of bacterial mutagens and imply that if important mutagen-forming atmospheric reactions occur, they likely occur in the winter and spring seasons as well as the photochemically more active summer and early fall periods.
Partially unfolded proteins efficiently penetrate cell membranes — implications for oral drug delivery
Authors: Sam J Milstein, Harry Leipold, Donald Sarubbi, Andrea Leone-Bay, Gwen M Mlynek, Joseph R Robinson, Marina Kasimova, Ernesto Freire
Journal: Journal of Controlled Release (1998)

We have previously reported on the biological activity of members of a library of low molecular weight compounds (carriers) that enable the oral delivery of proteins (Milstein, Proceedings of the 1995 Miami Bio/Technology Winter Symposium on Protein Engineering and Structural Biology, IRL Press at Oxford University Press, 1995, p. 13; Leone-Bay et al., J. Med. Chem. 38 (1995) 4263–4269; Leone-Bay et al., J. Med. Chem. 39 (1996) 2571–2578; 1, 2, 3). When rats or primates are orally administered a solution of carrier and either recombinant human α-interferon (rhIFN), insulin or recombinant human growth hormone (rhGH) significant serum concentrations of the proteins are detectable. The transport activity of these compounds is positively correlated with their structural effects on the protein molecules. Direct measurement of the interaction of these carrier molecules with the proteins indicates that they reversibly destabilize the native state of the molecule favoring a partially unfolded conformation. Apparently these intermediate protein conformations are transport competent and are able to be absorbed through the intestinal tissue and into the bloodstream. Since the measured binding of the carriers to the partially unfolded proteins is relatively weak (Kb=100 M−1) and the systemic activity of the proteins appears to be unaffected, the changes in the structure of the proteins are manifestly reversible.
A comparative study of human epidermal Langerhans cell densities in 10 anatomical sites in healthy and diseased skin
Authors: S. Taweechaisupapong, S. Angsubhakorn, S. Sriurairatana, N. Bhamarapravati
Journal: British Journal of Dermatology (1996)

Journal Article A comparative study of human epidermal Langerhans cell densities in 10 anatomical sites in healthy and diseased skin Get access S. Taweechaisupapong, S. Taweechaisupapong Department of Pathobiology, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand Search for other works by this author on: Oxford Academic Google Scholar S. Angsubhakorn, S. Angsubhakorn Department of Pathobiology, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand Search for other works by this author on: Oxford Academic Google Scholar S. Sriurairatana, S. Sriurairatana Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Rama 6 Road, Bangkok 10400, Thailand Search for other works by this author on: Oxford Academic Google Scholar N. Bhamarapravati N. Bhamarapravati Center for Vaccine Development. Institute of Science and Technology for Development, Mahidol University at Salaya, Nakhon Pathom 73170, Thailand Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 134, Issue 1, 1 January 1996, Pages 187–188, https://doi.org/10.1111/j.1365-2133.1996.tb07871.x Published: 01 January 1996
Genetic Susceptibility to Death from Coronary Heart Disease in a Study of Twins
Authors: Marjorie E. Marenberg, Neil Risch, Lisa F. Berkman, Birgitta Floderus, Ulf de Faire
Journal: New England Journal of Medicine (1994)

A family history of premature coronary heart disease has long been thought to be a risk factor for coronary heart disease. Using data from 26 years of follow-up of 21,004 Swedish twins born between 1886 and 1925, we investigated this issue further by assessing the risk of death from coronary heart disease in pairs of monozygotic and dizygotic twins.
Pharmacokinetic and Pharmacodynamic Modeling of an Anti–Interleukin-6 Chimeric Monoclonal Antibody (Siltuximab) in Patients with Metastatic Renal Cell Carcinoma
Authors: Thomas Puchalski, Uma Prabhakar, Qun Jiao, Birge Berns, Hugh M. Davis
Journal: Clinical Cancer Research (2010)

Interleukin-6 (IL-6) induces tumor growth, invasion, metastasis, and angiogenesis. Siltuximab (CNTO 328) is a chimeric, murine-human monoclonal antibody that specifically binds human IL-6 with high affinity. C-reactive protein (CRP) can be a pharmacodynamic (PD) marker of IL-6 bioactivity. Reductions in CRP may correlate with clinical activity and IL-6 bioactivity.Starting-dose selection for this study was based on a previous siltuximab study in multiple myeloma patients. Pharmacokinetic (PK)/PD modeling explored the relationship between siltuximab PK and CRP suppression following i.v. siltuximab infusion in a three-part phase I/II study in 68 metastatic renal cell carcinoma patients. Modeling results were then used to simulate and determine which siltuximab dosage regimens would maintain CRP suppression below the lower limit of quantification (4 mg/L). Siltuximab was given at 1, 3, 6, or 12 mg/kg at weeks 1 and 4 and then every 2 weeks for 2 cycles in part 1; at 3 or 6 mg/kg every 3 weeks for 4 cycles in part 2; and at 6 mg/kg every 2 weeks for 6 cycles in part 3.A two-compartment PK model adequately described the serum siltuximab concentration-time data. An inhibitory indirect response PD model examined the relationship between siltuximab concentrations and CRP suppression. PD parameter estimates seemed reliable and physiologically relevant. Simulations showed that 6 mg/kg siltuximab every 2 weeks or 9 mg/kg every 3 weeks would reduce serum CRP to below 4 mg/L.Using a stepwise design, PK/PD modeling was used to select the dose levels in this study. Furthermore, PK/PD modeling results were used to help select doses to be used in future siltuximab clinical development.
Abstract P4-01-04: The Impact of the Retinoblastoma Tumor Suppressor Pathway in Her2 Positive Breast Cancer Pathogenesis and Therapeutic Response
Authors: DB Rivadeneira, A Ertel, AK Witkiewicz, I Mercier, MP Lisanti, E. Knudsen
Journal: Cancer Research (2010)

Abstract Extensive studies have shown that breast cancer is associated with molecular aberrations that underlie the distinct subtypes of disease that exhibit differential prognosis and susceptibility to targeted therapeutic. A critical oncogenic event used to classify breast cancers is the amplification or overexpression of the human epidermal growth factor receptor 2 (Her2). Tumors harboring Her2 overexpression present aggressive characteristics related to metastatic spread and poor overall disease outcome. However, such tumors are also susceptible to targeted therapeutic agents which effectively impinge on this oncogene. Strikingly, those events that cooperate with Her2 and modulate susceptibility to targeted therapeutics remain poorly understood. Here the significance of the retinoblastoma tumor suppressor (RB) pathway in the context of Her2 positive breast cancer pathogenesis and therapeutic response was evaluated. In silico and histological analyses suggested that a subset of Her2 positive tumors exhibit compromised RB function. To model interactions between Her2 and the RB-pathway genetic deletion and knockdown strategies were employed in the context of Her2 driven tumors. These studies revealed that RB loss accelerated disease progression of such models and further enhanced the aggressive tumor phenotype. To delineate the functionality of the RB-pathway downstream from therapeutic interventions targeting Her2, two complimentary approaches were used. First, the ability to effectively intercede in Her2-positive tumors using drugs that specifically activate the RB-pathway was interrogated. The data revealed that specific CDK4/6 targeted therapies were highly effective at limiting the growth of Her2-positive tumor cells. Second, the impact of RB status on the response the Her2/EGFR antagonist lapatinib was evaluated. These studies demonstrated that loss of RB compromises the effectiveness of lapatinib in the treatment of Her2 positive breast cancer cell lines. Ongoing studies are evaluating the spontaneous mechanisms of resistance to Her2 targeted therapeutics and the significance of reestablishing RB function as a therapeutic alternative in such cancers. Together, these studies underscore the importance of the interplay between Her2 signaling and cell cycle control in breast cancer, and how this crosstalk influences the response to targeted therapeutics in the treatment of breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-01-04.
Distinguishing Benign from Malignant Euadrenal Masses
Authors: M. D. Gross, B. Shapiro, J. A. Bouffard, G. M. Glazer, I. R. Francis, G. P. Wilton, F. Khafagi, L. P. Sonda
Journal: Annals of Internal Medicine (1988)

Study Objective: To determine the efficacy of 131I-6-beta-iodomethylnorcholesterol (NP-59) adrenal scintigraphy in distinguishing benign from malignant euadrenal masses. Design: Case series of patients with incidentally discovered unilateral, euadrenal masses. Setting: Referral-based nuclear medicine clinics at university and affiliated Veterans Administration medical centers. Patients: Consecutive sample of 119 euadrenal patients with unilateral adrenal masses discovered on computed tomographic (CT) scans for reasons other than suspected adrenal disease. Interventions: Adrenal scintiscans done using 1 mCi of NP-59 intravenously, and gamma camera imaging, 5 to 7 days later. Measurements and Main Results: Mean lesion diameter was 3.3 ± 1.9 cm (SD) (95% CI: 2.9 to 3.6 cm). In 76 patients, NP-59 uptake lateralized to the abnormal adrenal seen on CT scans (concordant imaging), and in all of these patients, a diagnosis of adenoma was made by needle-aspiration biopsy, adrenalectomy, or extended follow-up with repeat CT scans that were unchanged at 6 months or later. Twenty-six patients had absent or markedly reduced NP-59 uptake in the glands identified as abnormal on CT scans (discordant imaging). These adrenal masses proved to be metastatic malignancies in 19 patients, primary adrenal neoplasms other than adenoma in 4, and adrenal cysts in 3. Bilateral, symmetric accumulation of NP-59 was seen in 17 patients, in whom the adrenal masses were shown to be metastatic malignancies in 2, and adenomas in 6 (the lesions in these cases being 2 cm or less in diameter), and lesions not truly involving the adrenal in the rest (periadrenal metastases in 4 and pseudoadrenal masses in 5). Sensitivity was 76% (26 of 34 patients; CI, 58% to 88%); specificity, 100% (85 of 85 patients; CI, 95% to 100%), and accuracy, 93% (111 of 119 patients; CI, 88% to 98%). Conclusions: Functional NP-59 scintigraphy can be used to accurately and noninvasively characterize many euadrenal masses; concordance of CT and NP-59 scans can be used to exclude the presence of a malignancy or other space-occupying adrenal lesion.
Metabolomic Imaging for Human Prostate Cancer Detection
Authors: Chin-Lee Wu, Kate W. Jordan, Eva M. Ratai, Jinhua Sheng, Christen B. Adkins, Elita M. DeFeo, Bruce G. Jenkins, Leslie Ying, W. Scott McDougal, Leo L. Cheng
Journal: Science Translational Medicine (2010)

Magnetic resonance spectroscopy can generate comprehensive maps of metabolites in the prostate that reveal cancerous regions, potentially guiding biopsies and prognosis.
Randomized trial of interferon beta-1a with or without ribavirin in Asian patients with chronic hepatitis C
Authors: Henry L. Y. Chan, Hong Ren, Wan C. Chow, Theodore Wee
Journal: Hepatology (2007)

The standard of care for chronic hepatitis C virus (HCV) infection, pegylated interferon (IFN) alpha plus ribavirin, results in a sustained virologic response (SVR) in approximately 50%-60% of patients. IFN beta is a potential alternative to IFN alpha. The aim of this study was to investigate the efficiency and durability of IFN beta and its combination with ribavirin in the naïve setting of chronic hepatitis C in Asian patients. In the initial randomized, double-blind phase, patients with chronic hepatitis C (n = 257) received 12 weeks of treatment with IFN beta-1a, 44 mug subcutaneously 3 times weekly, or a placebo. In the subsequent open-label phase, placebo nonresponders received 24 weeks of treatment with IFN beta-1a plus ribavirin, whereas patients receiving IFN beta-1a monotherapy received an additional 12 weeks of therapy. The primary outcome variable was SVR, which was defined as negative HCV RNA after weeks 24 and 48. A total of 34 of 128 patients (26.6%) receiving IFN beta-1a achieved an SVR versus 0 of 129 patients (0%) receiving the placebo (P < 0.001). In the IFN beta-1a/ribavirin group, 73 of 127 patients (57.5%) achieved an SVR [P < 0.001 versus IFN beta-1a; the adjusted odds ratio was 4.54 (95% confidence interval: 2.53, 8.13)]. In HCV genotype 1 patients, 37 of 80 patients (46.3%) treated with IFN beta-1a/ribavirin achieved an SVR versus 19 of 85 patients (22.4%) treated with IFN beta-1a (P = 0.001).IFN beta-1a produced a clear antiviral effect in Asian patients with chronic HCV infection. The addition of ribavirin to IFN beta-1a significantly increased the proportion of patients who achieved an SVR versus IFN beta-1a monotherapy.
Three-Dimensional Echocardiographic Analysis of Mitral Annular Dynamics
Authors: Melissa M. Levack, Arminder S. Jassar, Eric K. Shang, Mathieu Vergnat, Y. Joseph Woo, Michael A. Acker, Benjamin M. Jackson, Joseph H. Gorman, Robert C. Gorman
Journal: Circulation (2012)

Background— Proponents of flexible annuloplasty rings have hypothesized that such devices maintain annular dynamics. This hypothesis is based on the supposition that annular motion is relatively normal in patients undergoing mitral valve repair. We hypothesized that mitral annular dynamics are impaired in ischemic mitral regurgitation and myxomatous mitral regurgitation. Methods and Results— A Philips iE33 echocardiographic module and X7–2t probe were used to acquire full-volume real-time 3-dimensional transesophageal echocardiography loops in 11 normal subjects, 11 patients with ischemic mitral regurgitation and 11 patients with myxomatous mitral regurgitation. Image analysis was performed using Tomtec Image Arena, 4D-MV Assessment, 2.1 (Munich, Germany). A midsystolic frame was selected for the initiation of annular tracking using the semiautomated program. Continuous parameters were normalized in time to provide for uniform systolic and diastolic periods. Both ischemic mitral regurgitation (9.98±155 cm 2 ) and myxomatous mitral regurgitation annuli (13.29±3.05 cm 2 ) were larger in area than normal annuli (7.95±1.40 cm 2 ) at midsystole. In general, ischemic mitral regurgitation annuli were less dynamic than controls. In myxomatous mitral regurgitation, annular dynamics were also markedly abnormal with the mitral annulus dilating rapidly in early systole in response to rising ventricular pressure. Conclusions— In both ischemic mitral regurgitation and myxomatous mitral regurgitation, annular dynamics and anatomy are abnormal. Flexible annuloplasty devices used in mitral valve repair are, therefore, unlikely to result in either normal annular dynamics or normal anatomy.
GMC should not have thrown out case against neurologist, Singapore council says
Authors: Clare Dyer
Journal: BMJ (2006)

<h3>ABSTRACT</h3> Glutamine synthetase is the key enzyme of nitrogen assimilation, which is encoded in the first cistron of <i>glnALG</i> operon and is induced under nitrogen limiting conditions through transcriptional activation by NtrBC in <i>Salmonella</i> and <i>E. coli</i>. 2-oxoglutarate serves as the carbon skeleton of glutamate and glutamine, but how 2-oxoglutarate fluctuation is controlled in response to nitrogen availability remained unknown. We show that the <i>glnA</i> mRNA produces an Hfq-dependent GlnZ sRNA from its 3’ sUTR through RNase E-mediated cleavage. Through a base-pairing mechanism, GlnZ primarily regulates <i>sucA</i>, encoding the E1o component of 2-oxoglutarate dehydrogenase. In the cells grown on glutamine as the nitrogen source, the endogenous GlnZ represses the expression of SucA to redirect the carbon flow from the TCA cycle to the nitrogen assimilation pathway. This study also clarifies that the release of GlnZ sRNA from the <i>glnA</i> mRNA by RNase E is essential for the post-transcriptional regulation of <i>sucA</i>, and thus the mRNA coordinates the two independent functions to balance the supply and demand of the fundamental metabolites.
US court will rehear case that threatened health reform law
Authors: M. McCarthy
Journal: BMJ (2014)

A US Court of Appeals for the District of Columbia Circuit agreed on 4 September to rehear a case that had threatened to upend the Affordable Care Act.

In an earlier decision a three judge panel of the court had ruled, in a 2-1 majority, that the federal government did not have legal authority to provide subsidies to people who purchased health coverage through government run health insurance exchanges.

The exchanges were designed to provide a marketplace where people and families could comparison shop for health insurance and qualify for income based subsidies to help them pay their premiums. Of more than seven million people who have purchased coverage through the exchanges about 80% …
THE NEW ERA IN MEDICINE—WHAT IT MEANS TO CLEVELAND.
Authors: P. MAXWELL FOSHAY
Journal: JAMA (1902)

Before taking up for consideration this Society, its relations, its ideals, its accomplishments and its future prospects, it will be necessary to my purpose first to secure a broad view of our present duty by widening our horizon to the extent of clearly apprehending some, at least, of the present conditions of professional life in America. <h3>THE NEW ERA IN MEDICINE.</h3> At the risk of tiring you with a partial repetition of ideas that have been expressed elsewhere, but feeling that it is justified by its inherent importance, I earnestly urge you to recognize the fact that we are living in a new era of medicine. The change from past conditions has occurred so gradually, when compared to the span of one active life, that the transition has in large part escaped our notice. It is, however, of the utmost importance that we at once realize its full significance, in
Obstruction of Bowel due to Lesion in the Myenteric Plexus
Authors: N. H. Dyer, A. M. Dawson, B. F. Smith, I. P. Todd
Journal: BMJ (1969)

Two patients are described who were found to have a destructive lesion of the myenteric plexus. In one the upper small intestine was involved and the clinical picture was of recurrent pseudo-obstruction; in the other the lesion was in the distal colon and resulted in intractable constipation. The lesion cannot be demonstrated by conventional histological techniques, being seen only in silver preparations cut parallel to the bowel wall, and may have been overlooked in the past. The aetiology is unknown.
Immune therapy of metastatic melanoma developing after allogeneic bone marrow transplant
Authors: Michael Cecchini, Mario Sznol, Stuart Seropian
Journal: Journal for ImmunoTherapy of Cancer (2015)

Metastatic melanoma is frequently treated with immune activating therapy, which poses a theoretical risk of inducing graft versus host disease (GVHD) in those who have received allogeneic stem cell transplantation. The literature reporting the safety of immunotherapy in post transplant patients is limited. We report two patients with metastatic melanoma who received treatment with immunotherapy after allogeneic stem cell transplantation that did not result in GVHD.
Prevention of Postoperative Leg Vein Thrombosis by Electrical Muscle Stimulation. An Evaluation with 125I-Labelled Fibrinogen
Authors: N. L. Browse, D. Negus
Journal: BMJ (1970)

In a prospective trial of preventing deep vein thrombosis electrical stimulation of the calf muscles of one leg was used in 110 patients undergoing major surgery. Deep vein thrombosis was detected by means of the <sup>125</sup>I-fibrinogen uptake test in nine of the stimulated legs and in 23 of the unstimulated legs. It is suggested that this technique, which is both simple and effective, should be used on all patients undergoing major surgery.
Anaphylaxis in America: A national physician survey
Authors: Ashley M. Altman, Carlos A. Camargo, F. Estelle R. Simons, Philip Lieberman, Hugh A. Sampson, Lawrence B. Schwartz, F. Myron Zitt, Charlotte Collins, Michael Tringale, Marilyn Wilkinson, Robert A. Wood
Journal: Journal of Allergy and Clinical Immunology (2015)