tbuckley/cabot-search huggingface dataset:
RANK-L and RANK: T Cells, Bone Loss, and Mammalian Evolution
Authors: Lars E. Theill, William J. Boyle, Josef M. Penninger
Journal: Annual Review of Immunology (2002)

TNF and TNFR family proteins play important roles in the control of cell death, proliferation, autoimmunity, the function of immune cells, or the organogenesis of lymphoid organs. Recently, novel members of this large family have been identified that have critical functions in immunity and that couple lymphoid cells with other organ systems such as bone morphogenesis and mammary gland formation in pregnancy. The TNF-family molecule RANK-L (RANK-L, TRANCE, ODF) and its receptor RANK are key regulators of bone remodeling, and they are essential for the development and activation of osteoclasts. Intriguingly, RANK-L/RANK interactions also regulate T cell/dendritic cell communications, dendritic cell survival, and lymph node formation; T cell–derived RANK-L can mediate bone loss in arthritis and periodontal disease. Moreover, RANK-L and RANK are expressed in mammary gland epithelial cells, and they control the development of a lactating mammary gland during pregnancy and the propagation of mammalian species. Modulation of these systems provides us with a unique opportunity to design novel therapeutics to inhibit bone loss in arthritis, periodontal disease, and osteoporosis.
Verotoxin (Shiga Toxin) Sensitizes Renal Epithelial Cells to Increased Heme Toxicity
Authors: Martin Bitzan, Brandi B. Bickford, Gregory H. Foster
Journal: Journal of the American Society of Nephrology (2004)

Escherichia coli–derived verotoxins (VT; Shiga toxins) are causally related to the pathogenesis of enteropathic hemolytic uremic syndrome (HUS). Profound hemolysis is a defining feature of the disease, but it is not known whether the acute intravascular release of heme proteins contributes to HUS pathology. This study examined the biologic effects of hemin and VT by means of tubular epithelial-derived ACHN cells. Hemin at concentrations ≥200 μM caused cell rounding, spike formation, and detachment that was morphologically distinct from verocytotoxicity. VT caused apoptosis at concentrations >100 pM, as demonstrated by nuclear segmentation and poly(ADP-ribose) polymerase cleavage, whereas hemin-mediated injury of ACHN cells grown in serum-containing medium lacked attributes of programmed cell death. Pretreatment of ACHN monolayers with sublethal concentrations (1 to 10 pM) of VT for 12 to 18 h led to superadditive hemin-mediated cytotoxicity. This effect was not limited to ACHN cells, but was similarly noted in microvascular endothelial cells. Heme catabolism is regulated by (inducible) heme oxygenase-1 (HO-1). VT abrogated HO-1 expression in ACHN cells. Stimulation of cells for 6 h with CdCl2, which markedly increased HO-1 expression before the addition of VT, blunted subsequent hemin injury. In conclusion, VT augments hemin-induced toxicity in renal tubular epithelial cells that can be reversed by prior induction of HO-1. It is proposed that VT subverts the physiologic defense against heme proteins by interfering with the regulated expression of HO-1 and that this mechanism contributes to the renal pathology in patients with Escherichia coli–associated HUS.
One Thousand Vasectomies
Authors: I. G. Schraibman
Journal: BMJ (1974)

serotonin in the striatum.In the light of these findings and our present clinical finding it seems reasonable to conclude that mid- brain tremor is most probably due to combined interruption of the cerebellofugal pathway, the rubrospinal tract, and the ascending monoaminergic nervous pathways.-Weare, etc.,
A classification of psoriasis vulgaris according to phenotype
Authors: C.E.M. Griffiths, E. Christophers, J.N.W.N. Barker, R.J.G. Chalmers, S. Chimenti, G.G. Krueger, C. Leonardi, A. Menter, J.-P. Ortonne, L. Fry
Journal: British Journal of Dermatology (2006)

For nearly 200 years it has been appreciated that plaque psoriasis consists of a number of distinct clinical phenotypes. However, a reliable and simple stratification of clinical presentation of psoriasis is lacking. In the era of immunogenetic association studies and an advanced understanding of the pathomechanisms of psoriasis it is important that a classification of the disease according to phenotype is readily available. Such a classification would facilitate clinically relevant interpretation of investigational data. A meeting of the International Psoriasis Council produced a consensus on clinical phenotypes of psoriasis equally relevant to clinical practitioners and psoriasis researchers.
Does Anodyne Light Therapy Improve Peripheral Neuropathy in Diabetes?
Authors: Lawrence A. Lavery, Douglas P. Murdoch, Jayme Williams, David C. Lavery
Journal: Diabetes Care (2008)

The purpose of this study was to determine the efficacy of anodyne monochromatic infrared photo energy (MIRE) in-home treatments over a 90-day period to improve peripheral sensation and self-reported quality of life in individuals with diabetes.This was a double-blind, randomized, sham-controlled clinical trail. We randomly assigned 69 individuals with diabetes and a vibration perception threshold (VPT) between 20 and 45 V to two treatment groups: active or sham treatment. Sixty patients (120 limbs) completed the study. Anodyne units were used at home every day for 40 min for 90 days. We evaluated nerve conduction velocities, VPT, Semmes-Weinstein monofilaments (SWM) (4-, 10-, 26-, and 60-g monofilaments), the Michigan Neuropathy Screening Instrument (MNSI), a 10-cm visual analog pain scale, and a neuropathy-specific quality of life instrument. We used a nested repeated-measures multiple ANOVA design. Two sites (great toe and fifth metatarsal) were tested on both the left and right feet of each patient, so two feet were nested within each patient and two sites were nested within each foot. To analyze the ordinal SWM scores, we used a nonparametric factorial analysis for longitudinal data.There were no significant differences in measures for quality of life, MNSI, VPT, SWM, or nerve conduction velocities in active or sham treatment groups (P > 0.05).Anodyne MIRE therapy was no more effective than sham therapy in the treatment of sensory neuropathy in individuals with diabetes.
Dyspnoea after pneumonectomy
Authors: F W Smeenk, S P Twisk, E Berreklouw, H C Gooszen, P E Postmus
Journal: European Respiratory Journal (1991)

We report the case of a 61 yr old male, who developed a severe right-to-left shunt through a patent foramen ovale, in the absence of elevated right-sided heart pressures, two months after a left-sided pneumonectomy. This is considered to be a rare complication after pneumonectomy. However, taking into account the approximately 20% incidence of patent foramen ovale in the general population, we suggest that right-to-left shunting through an unsuspected foramen ovale or atrial septum defect should always be considered as a possible cause of otherwise unexplained hypoxaemia.
Respiratory Insufficiency in Poliomyelitis and Other Diseases
Authors: W. R. Russell
Journal: BMJ (1955)

Deep Treatment Learning (deepTL), a robust yet efficient deep learning-based semiparametric regression approach, is proposed to adjust the complex confounding structures in comparative effectiveness analysis of observational data, e.g. electronic health record (EHR) data, in which complex confounding structures are often embedded. Specifically, we develop a deep learning neural network with a score-based ensembling scheme for flexible function approximation. An improved semiparametric procedure is further developed to enhance the performance of the proposed method under finite sample settings. Comprehensive numerical studies have demonstrated the superior performance of the proposed methods as compared with existing methods, with a remarkably reduced bias and mean squared error in parameter estimates. The proposed research is motivated by a post-surgery pain study, which is also used to illustrate the practical application of deepTL. Finally, an R package, “deepTL”, is developed to implement the proposed method.
MACROPHAGE-MELANOMA CELL HETEROKARYONS
Authors: Saimon Gordon, Zanvil Cohn
Journal: The Journal of Experimental Medicine (1971)

Mouse peritoneal macrophages possess a specific plasma membrane receptor for antibody-coated particles. Sheep red cells coated with rabbit 7S antibody attach readily to the macrophage surface and are subsequently interiorized. The fusion of macrophage with nonphagocytic mouse melanoma cells produces heterokaryons in which the macrophage receptor is drastically altered. The receptor is present shortly after fusion and heterokaryons are actively phagocytic. The ability to bind and ingest red cells is, however, progressively lost over the next 12-24 hr and does not reappear thereafter. Exposure of heterokaryons to trypsin (1-100 microg/ml for 30 min at 37 degrees C) results in the reappearance of initial receptor activity and the unmasking of the surface receptor. This property is again lost upon subsequent cultivation. The masking process takes place when cells are cultivated in the absence of IgG so that the adsorption of antibody from the medium is not responsible for this phenomenon. Inhibition of heterokaryon protein synthesis preserves phagocytic activity in a reversible fashion and prevents the masking of macrophage receptors. Inhibition of melanoma RNA synthesis before fusion is also able to block subsequent masking, but is ineffective if delayed until after fusion. Ultraviolet irradiation of the melanoma cell before fusion prevents subsequent masking, whereas similar treatment of the macrophage has no effect. Cells differ markedly in their ability to mask the macrophage phagocytic receptor after fusion. Ehrlich ascites tumor cells mask the receptor rapidly, primary chick fibroblasts minimally, and embryonic chick erythrocytes not at all.
Authors' response: ‘What's nice about the new NICE guideline?’
Authors: John O'Reilly, Michael Rudolf
Journal: Thorax (2011)

We thank the correspondents for these kind and helpful comments.1 In adopting the Global Initiative on Obstructive Lung Disease (GOLD) classification of severity of airflow obstruction, the National Institute for Health and Clinical Excellence (NICE) guideline update has introduced consistency with international guidelines including those of the American Thoracic Society and the European Respiratory Society. The NICE guidelines note that this classification relates specifically to degrees of airflow obstruction which are arbitrary and may not be closely related to degrees of clinical severity in chronic obstructive pulmonary disease (COPD).2 The current use of the term ‘severe’ for airflow obstruction with forced expiratory volume in 1 s (FEV1)<50% in place of ‘moderate’ (NICE 2004) may also help to underline the potentially serious nature of …
Subclasses of cyclic AMP-specific phosphodiesterase in left ventricular muscle and their involvement in regulating myocardial contractility.
Authors: R E Weishaar, D C Kobylarz-Singer, R P Steffen, H R Kaplan
Journal: Circulation Research (1987)

Ventricular muscle contains a low Km, cyclic AMP-specific form of phosphodiesterase (PDE III), which is believed to represent the site of action for several of new cardiotonic agents including imazodan (CI-914), amrinone, cilostamide, and enoximone. However, species differences in the inotropic response to these agents have raised questions about the relationship between PDE III inhibition and cardiotonic activity. The present study demonstrates that these differences can be accounted for by the presence of two subclasses of PDE III in ventricular muscle and variations in the intracellular localization of these two enzymes. For these experiments, PDE III was initially isolated from canine, guinea pig, and rat left ventricular muscle. The results demonstrate that canine left ventricular muscle contains two functional subclasses of PDE III: an imazodan-sensitive form, which is membrane bound, and an imazodan-insensitive form, which is soluble. Although only weakly inhibited by imazodan, this latter enzyme is potently inhibited by the selective PDE III inhibitors, Ro 20-1724 and rolipram. Guinea pig ventricular muscle also contains the imazodan-sensitive subclass of PDE III. Unlike canine left ventricle, however, thi enzyme is soluble in the guinea pig. No membrane-bound subclass of PDE III was observed in the guinea pig. Rat left ventricle possesses only the soluble form of PDE III, which apparently represents a mixture of the imazodan-sensitive and imazodan-insensitive subclasses of PDE III. Measurement of in vivo contractility in these three species showed that imazodan exerts a potent positive inotropic effect only in the dog, in which the imazodan-sensitive subclass of PDE III is membrane bound.(ABSTRACT TRUNCATED AT 250 WORDS)
Prevalence of hepatitis C virus antibodies in the general population and in selected groups of patients in Limoges, France.
Authors: S Ranger, P Martin, M C Roussanne, F Denis
Journal: Gut (1993)

In this study of hepatitis C virus (HCV) infection prevalence in France, the prevalence of antibodies to HCV (as tested by second generation ELISA, with RIBA-2 confirmation in ELISA 2 positive samples) was found to be low (0.3%) in the healthy general population. HCV infection prevalence increased in the general population in association with African or Asian origin and risk factors such as bisexuality, previous history of transfusion, and intravenous drug abuse. The prevalence of anti-HCV infection was also higher in specific patient groups infected with HIV or a history of transfusion or haemodialysis.
Transient Receptor Potential Type Vanilloid 1 Suppresses Skin Carcinogenesis
Authors: Ann M. Bode, Yong-Yeon Cho, Duo Zheng, Feng Zhu, Marna E. Ericson, Wei-Ya Ma, Ke Yao, Zigang Dong
Journal: Cancer Research (2009)

Blockade of the transient receptor potential channel vanilloid subfamily 1 (TRPV1) is suggested as a therapeutic approach to pain relief. However, TRPV1 is a widely expressed protein whose function might be critical in various nonneuronal physiologic conditions. The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is overexpressed in many human epithelial cancers and is a potential target for anticancer drugs. Here, we show that TRPV1 interacts with EGFR, leading to EGFR degradation. Notably, the absence of TRPV1 in mice results in a striking increase in skin carcinogenesis. The TRPV1 is the first membrane receptor shown to have a tumor-suppressing effect associated with the down-regulation of another membrane receptor. The data suggest that, although a great deal of interest has focused on TRPV1 as a target for pain relief, the chronic blockade of this pain receptor might increase the risk for cancer development.
Chromosome studies in human sperm nuclei using fluorescence in-situ hybridization (FISH)
Authors: J Egozcue
Journal: Human Reproduction Update (1997)

The use of chromosome specific DNA probes labelled with fluorochromes and especially the combination of several probes has been used to indirectly study the chromosome constitution in condensed sperm nuclei by fluorescence in-situ hybridization (FISH), and has allowed to include this test in the protocol of study of infertile males. Still, if the test is to be valid, several strict conditions must be met, and some specific characteristics have to be taken into account. This becomes evident when comparing earlier results with more recent ones. The basic technical factors to be taken into account are the methods of chromatin decondensation, the number of spermatozoa and of individuals to study, the use of internal controls, the scoring criteria, the specificity of the probes and the possible existence of polymorphisms that may interfere with the detection of flourescent signals. In the last 7 or 8 years, a large number of papers has been published, describing the incidence of aneuploidies in controls, in individuals in whom a tendency to non-disjunction was suspected and in infertile males. Studies in controls have shown a considerable intra- and inter-individual variability in the frequency of aneuploidies, the tendency of some chromosomes to undergo non-disjunction (chromosome 21 and the sex chromosomes) and the importance of α-satellite polymorphisms when using centromere probes. In the control population, the frequency of aneuploidy per haploid set has been estimated at 6%. The incidence of aneuploidies in sperm nuclei for some of the chromosomes more frequently involved in trisomies is considerably higher than the incidence of these trisomies established through epidemiological data using the global incidence of chromosome abnormalities during the peri-implantation stage. In infertile males and in males with sex-chromosome abnormalities (usually with very low numbers of spermatozoa) the results show an increased incidence of sex chromosome aneuploidies and diploid (multi-aneuploid?) sperm nuclei. The results could be related to the higher incidence of chromosome abnormalities (especially sex-chromosome aneuploidies) observed in children conceived by intracytoplasmic sperm injection (ICSI).
Long-Term Effects of Cholesterol Lowering and Angiotensin-Converting Enzyme Inhibition on Coronary Atherosclerosis
Authors: Koon K. Teo, Jeffrey R. Burton, Christopher E. Buller, Sylvain Plante, Diane Catellier, Wayne Tymchak, Vladimir Dzavik, Dylan Taylor, Shinji Yokoyama, Terrence J. Montague
Journal: Circulation (2000)

Background —This long-term, multicenter, randomized, double-blind, placebo-controlled, 2×2 factorial, angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients. Methods and Results —There were a total of 460 patients: 230 received simvastatin and 230, a simvastatin placebo, and 229 received enalapril and 231, an enalapril placebo (some subjects received both drugs and some received a double placebo). Mean baseline measurements were as follows: cholesterol level, 5.20 mmol/L; triglyceride level, 1.82 mmol/L; HDL, 0.99 mmol/L; and LDL, 3.36 mmol/L. Average follow-up was 47.8 months. Changes in quantitative coronary angiographic measures between simvastatin and placebo, respectively, were as follows: mean diameters, −0.07 versus −0.14 mm ( P =0.004); minimum diameters, −0.09 versus −0.16 mm ( P =0.0001); and percent diameter stenosis, 1.67% versus 3.83% ( P =0.0003). These benefits were not observed in patients on enalapril when compared with placebo. No additional benefits were seen in the group receiving both drugs. Simvastatin patients had less need for percutaneous transluminal coronary angioplasty (8 versus 21 events; P =0.020), and fewer enalapril patients experienced the combined end point of death/myocardial infarction/stroke (16 versus 30; P =0.043) than their respective placebo patients. Conclusions —This trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients. The implications of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain, but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere.
αβ T Cell Receptor-positive Cells and Interferon-γ, but not Inducible Nitric Oxide Synthase, Are Critical for Granuloma Necrosis in a Mouse Model of Mycobacteria-induced Pulmonary Immunopathology
Authors: Stefan Ehlers, Jochen Benini, Heinz-Dieter Held, Christiane Roeck, Gottfried Alber, Stefan Uhlig
Journal: The Journal of Experimental Medicine (2001)

The immunological basis of tuberculin-induced necrosis, known for more than a century as “Koch's phenomenon,” remains poorly understood. Aerosol infection in mice with the highly virulent Mycobacterium avium strain TMC724 causes progressive pulmonary pathology strongly resembling caseating necrosis in human patients with tuberculosis. To identify the cellular and molecular mediators causing this pathology, we infected C57BL/6 mice and mice selectively deficient in recombinase activating gene (RAG)-1, αβ T cell receptor (TCR), γδ TCR, CD4, CD8, β2-microglobulin, interferon (IFN)-γ, interleukin (IL)-10, IL-12p35, IL-12p35/p40, or iNOS with M. avium by aerosol and compared bacterial multiplication, histopathology, and respiratory physiology in these mice. The bacterial load in the lung was similarly high in all mouse groups. Pulmonary compliance, as a surrogate marker for granulomatous infiltrations in the lung, deteriorated to a similar extent in all groups of mice, except in αβ TCR-knockout (KO) and IL-12–KO mice in which compliance was higher, and in IFN-γ and inducible nitric oxide synthase–KO mice in which compliance was reduced faster. Progressive caseation of pulmonary granulomas never occurred in αβ TCR-KO, IL-12–KO, and IFN-γ–KO mice and was reduced in CD4-KO mice. In summary, αβ TCR+ cells and IFN-γ are essential for the development of mycobacteria-induced pulmonary caseous necrosis. In contrast, high mycobacterial load and extensive granulomatous infiltration per se are not sufficient to cause caseation, nor is granuloma necrosis linked to the induction of nitric oxide.
The presence of two Fc receptors on mouse macrophages: evidence from a variant cell line and differential trypsin sensitivity.
Authors: J C Unkeless
Journal: The Journal of Experimental Medicine (1977)

A stable variant of a clone of the P388D1 macrophage line was isolated using four cycles of treatment with mouse IgG2a-rabbit anti-kappa complexes and rabbit complement. The variant had the same Ka and about the same number of sites per cell for IgG2a as the parent line. However, the variant had 10% as many binding sites for rabbit IgG in soluble antigen-antibody complexes, and the affinity of binding was threefold higher. This change in binding of complexes to cells of a cloned line without alternation of IgG2a binding provides evidence for the presence of two distinct Fc receptors. The two receptors could also be distiguished on the P388D1 line and on thioglycollate-induced mouse peritoneal macrophages by differential sensitivity to trypsinization. The receptors that bind monomeric IgG2a, sheep erythrocytes (SRBC) covalently bound with IgG2a or rabbit IgG using glutaraldehyde, and Sephadex beads coupled with IgG2a or rabbit IgG using cyanogen bromide activitation, is sensitive to trypsinization. The receptor that binds soluble rabbit antibody-antigen complexes, trinitrophenyl-SRBC and dinitrophenyl(DNP)-bovine serum albumin Sephadex beads coated with rabbit anti-DNP IgG is trypsin resitant, the observation that uncomplexed rabbit IgG oes not bind to the trypsin-resistant receptor, whereas the same IgG bound to its antigen does, suggests that conformational changes induced by the binding of ligand may be of consequence in macrophage function.