tbuckley/cabot-search huggingface dataset:
Changes in liver membrane potentials after partial hepatectomy in rats
Authors: X K Zhang, T Gauthier, F J Burczynski, G Q Wang, Y Gong, G Y Minuk
Journal: Hepatology (1996)

Changes in potential differences (PD) across hepatocyte membranes after partial hepatectomy may play an important role in hepatic homeostatic mechanisms and regenerative activity. To date, few studies have attempted to describe the extent and duration of such changes. In the present study, we documented PD values immediately before and for a 24-hour period after a partial hepatectomy (PHx) of 70% in healthy adult rats. We also documented PD changes after 30% and 90% PHx and PD values in different lobes of the same liver before and after PHx. Our findings showed that the liver depolarizes promptly (within 5 minutes of PHx) and that changes in PD are sustained for approximately 18 hours before returning to baseline values. We also observed that the magnitude of hepatic depolarization correlates with the extent of PHx. Finally, we did not observe regional differences in PD recordings from various lobes before and after PHx. These findings enhance our understanding of the physiological changes that occur in regenerating livers after PHx in rats.
Indeterminate results of QuantiFERON TB-2G test performed in routine clinical practice
Authors: Y. Kobashi, T. Sugiu, K. Mouri, Y. Obase, N. Miyashita, M. Oka
Journal: European Respiratory Journal (2009)

The present authors assessed risk factors that can promote indeterminate results of QuantiFERON TB-2G (QFT-2G; Cellestis Ltd, Carnegie, Australia) tests. The subjects were 704 patients with suspected tuberculosis (TB) and latent TB infection between January 2005 and December 2007. The QFT-2G test and the tuberculin skin test (TST) were performed for all subjects. If the results of the QFT-2G test were indeterminate, the test was repeated within 1 month. In total, 72 (10.2%) patients showed indeterminate results on the QFT-2G test. Indeterminate results were due to positive control failure in 68 (88.9%) patients and negative control failure in four patients. The results of the TST were negative for 64 patients showing indeterminate results, the remaining eight patients showed a positive response to the TST. Indeterminate results were significantly associated with elderly and immunocompromised patients. Lymphocytopaenia and hypoalbuminaemia were significantly associated with indeterminate laboratory findings. When the QFT-2G test was repeated for all patients showing indeterminate results, 12 (16.7%) patients demonstrated determinate results on the subsequent test. Indeterminate results of the QuantiFERON TB-2G test under routine clinical practice are not infrequent. When scoring QuantiFERON TB-2G test results for elderly and immunocompromised patients, one must be careful because the possibility of obtaining determinate results may be low even if the test is repeated.
COMPLETE HEART-BLOCK IN A CASE OF DIPHTHERIA
Authors: R. C. Allen
Journal: BMJ (1921)

Bsx 26Am=above cases post.anaesthetic vomiting-was -entirely absent, and fluids were given and retained immediately the operation was completed.The body nutrition therefore recommenced -at tlle earliest possible moment.'The clhief difference between these two cases was that in one the abdomen was opeued, whilst in the other it was not.It is suagested that the shock consequent upon opening the abdomen may be considerably reduced bv employing the above methods, and the prognosis, therefore, proportionately improved.
PET Imaging of Leptin Biodistribution and Metabolism in Rodents and Primates
Authors: Giovanni Ceccarini, Robert R. Flavell, Eduardo R. Butelman, Michael Synan, Thomas E. Willnow, Maya Bar-Dagan, Stanley J. Goldsmith, Mary J. Kreek, Paresh Kothari, Shankar Vallabhajosula, Tom W. Muir, Jeffrey M. Friedman
Journal: Cell Metabolism (2009)
Information, Computers, and Clinical Practice
Authors: Daniel Levinson
Journal: JAMA (1983)

INFORMATION management is integral to clinical practice. Clinicians and patients interact within a complex information matrix. The physician is an information manager who acquires, processes, stores, retrieves, and applies information related to (1) individual patient history and clinical course, (2) diagnostic and therapeutic protocols, (3) disease patterns in patient populations, (4) functioning of the health care system, and (5) the vast store of published knowledge. Little occurs in the clinical encounter that is not in some way related to obtaining, processing, or applying information. Optimal performance of clinical informational tasks has for years exceeded the cognitive capability of the human mind; the physician-patient interaction is an individual, handcrafted activity of uneven quality. The facts of the clinical history depend on the patient's often inadequate recall, the physician's intuitive problem-solving strategies, the time and emotional constraints of the interview, and an archaic record system. Diagnosis is an uncertain science, reflecting the
Light Chain Usage in Anti–double-stranded DNA B Cell Subsets: Role in Cell Fate Determination
Authors: Linda Spatz, Vladimir Saenko, Andrey Iliev, Lori Jones, Larisa Geskin, Betty Diamond
Journal: The Journal of Experimental Medicine (1997)

Two major mechanisms for the regulation of autoreactive B cells that arise in the bone marrow are functional silencing (anergy) and deletion. Studies to date suggest that low avidity interactions between B cells and autoantigen lead to B cell silencing, whereas high avidity interactions lead to deletion. Anti–double stranded (ds) DNA antibodies represent a pathogenic autospecificity in Systemic Lupus Erythematosus (SLE). An understanding of their regulation is critical to an understanding of SLE. We now demonstrate in a transgenic model in which mice express the heavy chain of a potentially pathogenic anti-DNA antibody that antibody affinity for dsDNA does not alone determine the fate of anti-dsDNA B cells. B cells making antibodies with similar affinities for dsDNA are regulated differently, depending on light chain usage. A major implication of this observation is that dsDNA may not be the self antigen responsible for cell fate determinations of anti-dsDNA B cells. Light chain usage may determine antigenic crossreactivity, and cross-reactive antigens may regulate B cells that also bind dsDNA.
A new human Duffy blood group specificity defined by a murine monoclonal antibody. Immunogenetics and association with susceptibility to Plasmodium vivax.
Authors: M E Nichols, P Rubinstein, J Barnwell, S Rodriguez de Cordoba, R E Rosenfield
Journal: The Journal of Experimental Medicine (1987)

A new Duffy specificity, Fy6, defined by a murine monoclonal antibody of the IgG1 kappa class, is related to susceptibility to malarial invasion. In humans, Fy6 is present on the red cells of all persons except those of the Fy(a-b-) type, a distribution resembling that of Fy3. However proteolytic enzyme treatment of red cells enhances the reactivity of Fy3, whereas Fy6, like Fya and Fyb, is susceptible to degradation by this process. The number of Fy6 sites on human red cells was found to be 12,200 per cell, in close agreement with earlier estimates of the number of Fya sites. Anti-Fy6 reacted in western blots with a membrane glycoprotein of approximately 46,000 Mr, not significantly different from that of a molecule known to bear the Fya determinant. The Fy6 epitope is shown to be present on the red cells of some but not all nonhuman primate species, where it has a distribution not only distinctly different from Fya, Fyb, and Fy3, but in close accordance with susceptibility to penetration by Plasmodium vivax. Thus, the red cells of two species of macaques (Macaca mulatta and M. fascicularis), which are invaded by Plasmodium knowlesi but not by P. vivax are shown to have other Duffy antigens but to be devoid of Fy6. It appears, therefore, that the red cell epitopes used by these closely related species are distinct, and that susceptibility to P. vivax merozoite penetration is dependent on the presence of Fy6.
Effects of olsalazine and sulphasalazine on jejunal and ileal water and electrolyte absorption in normal human subjects.
Authors: A H Raimundo, D H Patil, P G Frost, D B Silk
Journal: Gut (1991)

The effect of sulphasalazine and olsalazine on jejunal and ileal water and electrolyte absorption was investigated in normal subjects by a steady state intestinal perfusion of a physiological glucose bicarbonate electrolyte solution in the absence and presence of increasing concentrations of each drug. (Olsalazine 0.25 g/l, 1.0 g/l, jejunum; 0.5 g/l, 1.0 g/l, ileum; sulphasalazine 0.25 g/l, 0.5 g/l, 2.0 g/l jejunum; 1.0 g/l, 2.0 g/l, ileum.) In the jejunum olsalazine at 1.0 g/l significantly inhibited water, sodium, chloride, and potassium absorption (p less than 0.05). In the ileum olsalazine at 0.5 and 1 g/l significantly inhibited glucose uptake (p less than 0.04) and water absorption (p less than 0.03). In the jejunum sulphasalazine had a dose related and significant inhibitory effect on water, bicarbonate, and sodium absorption and at 2.0 g/l an inhibitory effect on chloride, potassium (p less than 0.005), and glucose (p less than 0.05) absorption. In the ileum sulphasalazine had no significant effect on water and electrolyte absorption. All inhibitory effects were rapidly reversible. These data show that unexplained diarrhoea in patients with ulcerative colitis treated with olsalazine may occur as a consequence of inhibition of water and electrolyte absorption in the small intestine and that the mechanisms of inhibition of sulphasalazine and olsalazine are different.
Modulation of Gene Expression by Tumor-Derived p53 Mutants
Authors: Mariano J. Scian, Katherine E. R. Stagliano, Michelle A. Ellis, Sajida Hassan, Melissa Bowman, Michael F. Miles, Swati Palit Deb, Sumitra Deb
Journal: Cancer Research (2004)

Abstract p53 mutants with a single amino acid substitution are overexpressed in a majority of human cancers containing a p53 mutation. Overexpression of the mutant protein suggests that there is a selection pressure on the cell indicative of an active functional role for mutant p53. Indeed, H1299 cells expressing mutant p53-R175H, p53-R273H or p53-D281G grow at a faster rate compared with a control cell line. Using p53-specific small interfering RNA, we show that the growth rate of mutant p53-expressing cells decreases as mutant p53 level decreases, demonstrating that the increased cellular growth is dependent on p53 expression. Increased growth rate is not observed for H1299 cell clones expressing mutant p53-D281G (L22Q/W23S), which has been shown to be defective in transactivation in transient transcriptional assays. This shows that the increased growth rate imparted by mutant p53 in H1299 cells requires the transactivation function of mutant p53. By performing microarray hybridization analyses, we show that constitutive expression of three common p53 mutants (p53-R175H, p53-R273H, and p53-D281G) in H1299 human lung carcinoma cells evokes regulation of a common set of genes, a significant number of which are involved in cell growth regulation. Predictably, H1299 cells expressing p53-D281G (L22Q/W23S) are defective in up-regulating a number of these genes. The differences in expression profiles induced by individual p53 mutants in the cells may be representative of the p53 mutants and how they can affect gene expression resulting in the observed “gain of function” phenotypes (i.e., increased growth rate, decreased sensitivity to chemotherapeutic agents, and so forth).
A Phase I Study of Cantuzumab Mertansine Administered as a Single Intravenous Infusion Once Weekly in Patients with Advanced Solid Tumors
Authors: Paul R. Helft, Richard L. Schilsky, Frank J. Hoke, Daphne Williams, Hedy L. Kindler, Evie Sprague, Mark DeWitte, Helen K. Martino, John Erickson, Lini Pandite, Mark Russo, John M. Lambert, Maria Howard, Mark J. Ratain
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose is to determine the maximum-tolerated dose, assess the toxicities, characterize the pharmacokinetic behavior, and seek preliminary evidence of biological activity of cantuzumab mertansine when administered as a weekly i.v. infusion without interruption. Experimental Design: Patients with incurable solid tumors that expressed the target antigen for cantuzumab mertansine, CanAg, were treated with doses of cantuzumab mertansine ranging from 40 to 138 mg/m2. The maximum-tolerated dose was defined as the highest dose at which no more than 1 of 6 patients experienced dose-limiting toxicity. Plasma concentrations of cantuzumab mertansine and total humanized antibody were determined, and area under the plasma concentration-time curve (to the last measured concentration) was calculated. Results: Thirty-nine patients received a total of 280 weekly doses of cantuzumab mertansine. Acute, transient elevation of the hepatic transaminases and reversible fatigue were identified as the dose-limiting toxicities at the highest dose level. The maximum-tolerated dose was determined to be 115 mg/m2/week. Evidence of clinical activity was noted in 3 patients. Pharmacokinetic analyses revealed that the pharmacokinetic variability was moderate, without evidence of dose dependency. Furthermore, the drug had a long terminal half-life (∼40 h). Conclusions: This study identified a safe and tolerable dose of the novel immunoconjugate prodrug cantuzumab mertansine. The evidence of antitumor activity suggests that additional clinical development is warranted, with a focus on tumors that express high levels of CanAg and which are known to be sensitive to antimicrotubule agents.
Clinical significance of cyclin D1 expression in patients with node-positive breast carcinoma treated with adjuvant therapy
Authors: P. Pelosio, M. Barbareschi, E. Bonoldi, A. Marchetti, P. Verderio, O. Caffo, P. Bevilacqua, P. Boracchi, F. Buttitta, R. Barbazza, P. Dalla Palma, G. Gasparini
Journal: Annals of Oncology (1996)
Total skin electron radiation in the management of mycosis fungoides: Consensus of the European Organization for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Project Group
Authors: Glenn W. Jones, Barry M. Kacinski, Lynn D. Wilson, Rein Willemze, Margaret Spittle, Gerda Hohenberg, Leonore Handl-Zeller, Franz Trautinger, Robert Knobler
Journal: Journal of the American Academy of Dermatology (2002)
EBNA1-specific T cells from patients with multiple sclerosis cross react with myelin antigens and co-produce IFN-γ and IL-2
Authors: Jan D. Lünemann, Ilijas Jelčić, Susanne Roberts, Andreas Lutterotti, Björn Tackenberg, Roland Martin, Christian Münz
Journal: The Journal of Experimental Medicine (2008)

Symptomatic primary Epstein-Barr virus (EBV) infection and elevated humoral immune responses to EBV are associated with an increased risk of developing multiple sclerosis (MS). We explored mechanisms leading to this change in EBV-specific immunity in untreated patients with MS and healthy virus carriers matched for MS-associated HLA alleles. MS patients showed selective increase of T cell responses to the EBV nuclear antigen 1 (EBNA1), the most consistently recognized EBV-derived CD4+ T cell antigen in healthy virus carriers, but not to other EBV-encoded proteins. In contrast, influenza and human cytomegalovirus–specific immune control was unchanged in MS. The enhanced response to EBNA1 was mediated by an expanded reservoir of EBNA1-specific central memory CD4+ T helper 1 (Th1) precursors and Th1 (but not Th17) polarized effector memory cells. In addition, EBNA1-specific T cells recognized myelin antigens more frequently than other autoantigens that are not associated with MS. Myelin cross-reactive T cells produced IFN-γ, but differed from EBNA1-monospecific cells in their capability to produce interleukin-2, indicative of a polyfunctional phenotype as found in controlled chronic viral infections. Our data support the concept that clonally expanded EBNA1-specific CD4+ T cells potentially contribute to the development of MS by cross-recognition of myelin antigens.
The bitterest pill
Authors: Des Spence
Journal: BMJ (2007)

In 2004 I attended a parliamentary subcommittee meeting and sat with stars of the medical firmament such as Andrew Hexheimer, David Healy, and Ike Iheanacho. I was there simply as an honest witness to the excesses I had seen and to express support for the No Free Lunch group (www.nofreelunch-uk.org). I was a mere pimple on an ailing and delirious drug industry being dragged down by a virulent infection called marketing.

After all its high living, huge profits, and dancing provocatively on the tops of stock market …
Sickness among Workers in Alumina
Authors: A. B. Hill
Journal: BMJ (1936)

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~KWA.N.L' Chronic bronchitis was diagnosed in a man who had been gassed in the war and treated in hospital for four or five weeks.He had had several attacks of chest trouble since that time.In a few others slight adventitious sounds were found, with no other departure from normal.In the last column of Table I the conclusions arrived at on interpretation of the clinical and radiological data are indicated for each age group by the letters A, B, C, and D, which have the following significance:A.-Nothing found in the clinical or radiological examina- tions which suggests any changes in the lungs: thirty cases.B.-Changes in the lungs found clinically and radiologically: five cases, in which the diagnoses were:(1) consistent with history of previous pneumonia (2) asthma; (3) catarrh; (4) chronic bronchitis ; (5) slight fibrosis or senile changes.C.-Changes in the lungs found clinically only: one case showed slight signs of bronchial catarrh.D.-Changes in the lungs found radiologically only: fourteen cases.The changes in two were doubtful and in all the others they were of slight degree.Classification of the changes and the clinical findings are as follows:
The Primate Cortical Auditory System and Neural Representation of Conspecific Vocalizations
Authors: Lizabeth M. Romanski, Bruno B. Averbeck
Journal: Annual Review of Neuroscience (2009)

Over the past decade, renewed interest in the auditory system has resulted in a surge of anatomical and physiological research in the primate auditory cortex and its targets. Anatomical studies have delineated multiple areas in and around primary auditory cortex and demonstrated connectivity among these areas, as well as between these areas and the rest of the cortex, including prefrontal cortex. Physiological recordings of auditory neurons have found that species-specific vocalizations are useful in probing the selectivity and potential functions of acoustic neurons. A number of cortical regions contain neurons that are robustly responsive to vocalizations, and some auditory responsive neurons show more selectivity for vocalizations than for other complex sounds. Demonstration of selectivity for vocalizations has prompted the question of which features are encoded by higher-order auditory neurons. Results based on detailed studies of the structure of these vocalizations, as well as the tuning and information-coding properties of neurons sensitive to these vocalizations, have begun to provide answers to this question. In future studies, these and other methods may help to define the way in which cells, ensembles, and brain regions process communication sounds. Moreover, the discovery that several nonprimary auditory cortical regions may be multisensory and responsive to vocalizations with corresponding facial gestures may change the way in which we view the processing of communication information by the auditory system.
<i>p21</i> Loss Cooperates with INK4 Inactivation Facilitating Immortalization and <i>Bcl-2</i>–Mediated Anchorage-Independent Growth of Oncogene-Transduced Primary Mouse Fibroblasts
Authors: Christopher J. Carbone, Xavier Graña, E. Premkumar Reddy, Dale S. Haines
Journal: Cancer Research (2007)

Abstract The INK4 and CIP cyclin-dependent kinase (Cdk) inhibitors (CKI) activate pocket protein function by suppressing Cdk4 and Cdk2, respectively. Although these inhibitors are lost in tumors, deletion of individual CKIs results in modest proliferation defects in murine models. We have evaluated cooperativity between loss of all INK4 family members (using cdk4r24c mutant alleles that confer resistant to INK4 inhibitors) and p21Waf1/Cip1 in senescence and transformation of mouse embryo fibroblasts (MEF). We show that mutant cdk4r24c and p21 loss cooperate in pRb inactivation and MEF immortalization. Our studies suggest that cdk4r24c mediates resistance to p15INK4B/p16INK4A that accumulates over passage, whereas loss of p21 suppresses hyperoxia-induced Cdk2 inhibition and pRb dephosphorylation on MEF explantation in culture. Although cdk4r24c and p21 loss cooperate in H-rasV12/c-myc–induced foci formation, they are insufficient for oncogene-induced anchorage-independent growth. Interestingly, p21−/−; cdk4r24c MEFs expressing H-rasV12 and c-myc display detachment-induced apoptosis and are transformed by c-myc, H-rasV12, and Bcl-2. We conclude that the INK4 family and p21 loss cooperate in promoting pRb inactivation, cell immortalization, and H-rasV12/c-myc–induced loss of contact inhibition. In addition, absence of pRb function renders H-rasV12 + c-myc–transduced fibroblasts prone to apoptosis when deprived of the extracellular matrix, and oncogene-induced anchorage-independent growth of pocket protein–deficient cells requires apoptotic suppression. [Cancer Res 2007;67(9):4130–7]
Cross-reactivity between H-2K and H-2D products. I. Evidence for extensive and reciprocal serological cross-reactivity
Authors: DB Murphy, DC Shreffler
Journal: The Journal of Experimental Medicine (1975)

Serological cross-reactivity between the products of the H-2K and H-2D genes has been demonstrated by a design in which antibody was produced against determinants controlled by one locus (e .g . H-2K(k)), and then tested against the product of the opposite locus (e .g . H-2D(d)). A total of 13 out of 18 such test combinations exhibited H-2K-H-2D cross-reactivity. The presence or absence of cross-reactivity was reciprocal in most cases (i.e. antibody directed against the H-2K(k) gene product reacted with H-2(d) determinants, and antibody directed against the H-2D(d) gene product reacted with H-2K(k) determinants). An Ia-like reaction was detected with one antiserum which implied possible cross-reactivity between the products of two discrete la genes.