tbuckley/cabot-search huggingface dataset:
Conservation and divergence of gene families encoding components of innate immune response systems in zebrafish
Authors: Cornelia Stein, Mario Caccamo, Gavin Laird, Maria Leptin
Journal: Genome biology (2007)

The zebrafish has become a widely used model to study disease resistance and immunity. Although the genes encoding many components of immune signaling pathways have been found in teleost fish, it is not clear whether all components are present or whether the complexity of the signaling mechanisms employed by mammals is similar in fish. We searched the genomes of the zebrafish Danio rerio and two pufferfish for genes encoding components of the Toll-like receptor and interferon signaling pathways, the NLR (NACHT-domain and leucine rich repeat containing) protein family, and related proteins. We find that most of the components known in mammals are also present in fish, with clearly recognizable orthologous relationships. The class II cytokines and their receptors have diverged extensively, obscuring orthologies, but the number of receptors is similar in all species analyzed. In the family of the NLR proteins, the canonical members are conserved. We also found a conserved NACHT-domain protein with WD40 repeats that had previously not been described in mammals. Additionally, we have identified in each of the three fish a large species-specific subgroup of NLR proteins that contain a novel amino-terminal domain that is not found in mammalian genomes. The main innate immune signaling pathways are conserved in mammals and teleost fish. Whereas the components that act downstream of the receptors are highly conserved, with orthologous sets of genes in mammals and teleosts, components that are known or assumed to interact with pathogens are more divergent and have undergone lineage-specific expansions.
Toxicity of Intrathecally Administered Pancreatic Dornase
Authors: Richard H. Parker
Journal: JAMA (1965)

DEATH AND MORBIDITY from pyogenic meningitis have been dramatically reduced since the discovery of antimicrobial agents. Yet, 5% to 25% of patients with this disease die, and 5% to 25% who survive have neurological complications, in spite of seemingly appropriate antimicrobial therapy.<sup>1</sup>Since these fatalities and complications may be related to the presence of extensive inflammatory exudate over the meninges, enzymatic debridement has been suggested as an adjunct to therapy.<sup>2</sup>Virtual absence of antigenicity distinguishes pancreatic dornase from deoxyribonuclease (DNA-ase) produced by streptococci. Thus, pancreatic dornase was selected for intrathecal injection, as a means of liquefying the exudate from pyogenic meningitis. In the few reported cases, there has been no mention of toxicity from the intrathecal administration of pancreatic dornase.<sup>2,3</sup> This case is reported because fever, nuchal rigidity, and elevated cerebrospinal-fluid-protein levels occurred after the intrathecal injection of pancreatic dornase. Reporting of this single case is further
Implantation of the Ureters.—A Reply.
Authors: Reuben Peterson
Journal: JAMA (1901)

Chicago, April 29, 1901. <h3>To the Editor:</h3> —It gives me great pleasure to be afforded an opportunity of replying to Dr. Fowler's criticism (see last week'sJournal) of certain conclusions appearing in my article on "Ureteral Anastomosis" recently published inThe Journal(Feb. 16-March 23). The particular conclusion objected to is the third among the General Conclusions, and reads as follows: "All efforts to prevent ascending renal infection in animals or man, where the ureter has been implanted (into the intestine) without its vesical orifice have proved futile." In order to show this conclusion false, Dr. Fowler points to his case of uretero-rectal implantation, where the patient has survived bilateral uretero-rectal implantation by the Fowler method 4½ years and is to-day<i>apparently</i>in perfect health. What grounds have I for assuming that this patient's kidneys, as a result of the operative procedure, have been infected, "but that the infection has
Thermoreversible gelation polymer induces the emergence of hepatic stem cells in the partially injured rat liver
Authors: Masaki Nagaya, Sunao Kubota, Noboru Suzuki, Katsuya Akashi, Toshihiro Mitaka
Journal: Hepatology (2006)

Focal injury of the adult liver causes formation of granulomatous tissue and fibrosis. When thermoreversible gelation polymer (TGP) was applied to such defects of the rat liver, complete recovery of hepatic tissues was observed without granulation. We analyzed the mechanism of the regeneration. TGP is a chemically synthesized biocompatible polymer material whose sol-gel transition is reversible by changing the temperature. Cooled TGP was poured into a penetration lesion of the rat liver. Immunohistochemistry and polymerase chain reaction were carried out using tissues and cultured cells isolated from ductular structures. Immunocytochemical and ultrastructural analyses were also conducted. Seven days after TGP treatment, ductular reactions were observed around the wound and ductules elongated to the injured area. Cells in the structures were alpha-fetoprotein (AFP) positive, albumin+, CK19+, c-Kit+, and Thyl+. Hepatocyte-like cells possessing glycogen appeared around the tips of the ductules from day 9. The defect was completely replaced with hepatocytes by day 28. Cells isolated from the ductules expressed Musashi-1, c-Kit, Thyl, AFP, albumin, transferrin, connexin 43, and CK19. When the cultured cells were covered by TGP, they rapidly proliferated to form colonies, whereas without TGP cells gradually died. Morphologically and ultrastructurally the cells were similar to hepatocytes. They expressed not only albumin and transferrin but TAT, CYP2E1, and CCAAT/enhancer binding protein a. Some cells formed bile canaliculus-like structures. In conclusion, TGP may trigger the initiation of hepatic stem cells in biliary ductules, and stem cell activation may occur even in the regeneration of the normal liver.
Electrophysiologic Identification of the Specialized Conduction System in Corrected Transposition of the Great Arteries
Authors: JOEL KUPERSMITH, EHUD KRONGRAD, WELTON M. GERSONY, FREDERICK O. BOWMAN
Journal: Circulation (1974)

Electrophysiologic identification of the specialized conduction system was performed during open-heart surgery in two cases of corrected transposition of the great arteries (1-TGA) with situs solitus, dextrocardia or dextroversion and membranous ventricular septal defect (VSD). In one case there was accompanying subvalvlar pulmonary stenosis and in the other there was an Ebstein-like deformity of the systemic atrioventricular (A-V) valve. Electrograms were recorded throughout the right atrium and morphologic left ventricle in the case with subvalvar pulmonary stenosis and throughout the left atrium and morphologic right ventricle in the case with the Ebstein-like deformity of the systemic A-V valve. Specialized conduction system electrograms were recorded exclusively at sites anterior to the membranous VSD in both cases and at no other sites in the respective atrium or ventricle studied. There was first degree A-V block in both cases and in each the site within the specialized conduction system of this delay was proximal to the specialized fiber electrogram recording sites and thus probably proximal to the bifurcation of the bundle branches. In addition, on, the Ebstein-like deformity of the systemic A-V valve present in one case was confirmed by directly recording ventricular electrograms in an area of "atrialized-ventricle above the valve.
Thyroid hormone stimulation of phosphatidylcholine synthesis in cultured fetal rabbit lung.
Authors: P L Ballard, M L Hovey, L K Gonzales
Journal: Journal of Clinical Investigation (1984)

To investigate the mechanism of thyroid hormone action on pulmonary surfactant synthesis, we characterized the effect of triiodothyronine on phosphatidylcholine synthesis in cultured fetal rabbit lung. Since glucocorticoids stimulate surfactant synthesis and reduce the incidence of Respiratory Distress Syndrome in premature infants, we also examined the interaction of triiodothyronine and dexamethasone. The rate of choline incorporation into phosphatidylcholine was determined in organ cultures of rabbit lung maintained in serum-free Waymouth's medium. In 23-d lung cultured for 72 h, the increase in choline incorporation with triiodothyronine alone, dexamethasone alone, and triiodothyronine plus dexamethasone was 50, 62, and 161%, respectively. Both triiodothyronine and dexamethasone also increased incorporation rates with glucose, glycerol, and acetate as precursors, and stimulation with triiodothyronine plus dexamethasone was at least additive. Dexamethasone, but not triiodothyronine, affected distribution of radioactivity from [3H] acetate among phospholipids. Stimulation was first detected 8-12 h after addition of triiodothyronine, and then increased in a linear fashion. With triiodothyronine plus dexamethasone, stimulation was maximal at 48-72 h, and was supra-additive at all times. Exposure of cultured lung to dexamethasone enhanced the subsequent response to triiodothyronine, but not vice versa. When triiodothyronine was removed from cultures, there was no further stimulation and the triiodothyronine effect was partially reversed within 24 h. Half-maximal stimulation of choline incorporation occurred at a triiodothyronine concentration (0.10 nM) very similar to the dissociation constant for triiodothyronine binding to nuclear receptor (0.11 nM). The relative potencies of thyroid hormone analogs for nuclear binding and stimulation of phosphatidylcholine synthesis were also similar: triiodothyroacetic acid greater than triiodothyronine-proprionic acid greater than L-triiodothyronine approximately D-triiodothyronine much greater than thyroxine much greater than 3,5-diethyl-3'-isopropyl-DL-thyronine approximately 3,5-dimethyl-3'-isopropyl-L-thyronine approximately reverse triiodothyronine. The effect of triiodothyronine was blocked by the presence of either actinomycin D or cycloheximide, inhibitors of ribonucleic acid and protein synthesis, respectively. We conclude that triiodothyronine stimulates phosphatidylcholine synthesis by a process involving nuclear receptors and de novo ribonucleic acid and protein synthesis. These findings support the concept that endogenous triiodothyronine has a physiologic role in lung maturation and suggest that a combined antenatal therapy with thyroid hormone and glucocorticoid may be useful for prevention of Respiratory Distress Syndrome in the premature infant.
PD-L1 negatively regulates CD4+CD25+Foxp3+ Tregs by limiting STAT-5 phosphorylation in patients chronically infected with HCV
Authors: Debora Franceschini, Marino Paroli, Vittorio Francavilla, Melissa Videtta, Stefania Morrone, Giancarlo Labbadia, Antonella Cerino, Mario U. Mondelli, Vincenzo Barnaba
Journal: Journal of Clinical Investigation (2009)

CD4+CD25+Foxp3+ Tregs suppress autoimmune responses. In addition, they limit T cell responses during chronic infection, thereby minimizing T cell–dependent immunopathology. We sought to investigate how Tregs are regulated in the livers of patients chronically infected with HCV, where they control the balance between an adequate protective immune response and suppression of immunopathology. We found that, despite accumulating and proliferating at sites of infection in the livers of patients chronically infected with HCV, Tregs were relatively less expanded than CD4+CD25+Foxp3– effector T cells. The relative lower expansion of intrahepatic Tregs coincided with their upregulation of programmed death–1 (PD-1). PD-1 expression inversely correlated with both Treg proliferation and clinical markers of immune suppression in vivo. Consistent with the possibility that PD-1 controls Tregs, blockade of the interaction between PD-1 and programmed death–1 ligand 1 (PD-L1) enhanced the in vitro expansion and function of Tregs isolated from the livers of patients chronically infected with HCV. Blockade of the interaction between PD-L1 and B7.1 also improved the proliferation of these cells. Interestingly, both PD-1 and phosphorylated STAT-5 were overexpressed in intrahepatic Tregs in a parallel fashion in steady disease conditions, and in an alternate-fluctuating fashion during the course of severe hepatitis reactivation. Notably, PD-L1 blockade upregulated STAT-5 phosphorylation in Tregs ex vivo. These data suggest that PD-L1 negatively regulates Tregs at sites of chronic inflammation by controlling STAT-5 phosphorylation.
ABC of major trauma. Management of hypovolaemic shock.
Authors: P J Baskett
Journal: BMJ (1990)

Class II Class IlIlHypovolaemic shock is a clinical state in which tissue perfusion is rendered relatively inadequate by loss of blood or plasma after injury to the vascular tree.A reduction in blood volume produces a fall in systolic pressure, which triggers a sympathetic catecholamine response that results in peripheral vasoconstriction, a rise in pulse rate, and a reduction in pulse pressure.The tachycardia and increased cardiac contractility lead to an increased myocardial oxygen requirement.Blood flow to the skin and peripheral tissues is reduced in an effort to preserve reasonable perfusion of vital organs such as the brain, heart, liver, and kidneys.If there is continuing blood loss inadequate tissue perfusion results in anaerobic mnetabolism, acidosis, and reduction in the performance of the vital organs.Further myocardial depression accelerates this process, and pain stimuli add to the sympathetic outburst.Pale Pale Anxious, agressive, or drowsy Pale and cold Ashen Drowsy, confused, or unconscious * Hypotension (due to hypovolaemia, perhaps followed by myocardial insufficiency) * Skin pallor (vasoconstriction due to catecholamine release) * Tachycardia (due to catecholamine release) * Confusion, aggression, drowsiness, and coma (due to cerebral hypoxia and acidosis) * Tachypnoea (due to hypoxia and acidosis) * General weakness (due to hypoxia and acidosis) * Thirst (due to hypovolaemia) * Reduced urine output (due to reduced perfusion).
Endoscopic Transhiatal Drainage of a Mediastinal Pancreatic Pseudocyst
Authors: W. Mohl, C. Moser, B. Kramann, S. Zeuzem, A. Stallmach
Journal: Endoscopy (2004)

Transgastric drainage of pancreatic pseudocysts guided by endoscopic ultrasound is now a standard procedure in experienced hands [1] [2]. Mediastinal pancreatic pseudocysts are relatively rare; they result from extension of pancreatic pseudocysts into the mediastinum [3] [4] [5]. Most patients are symptomatic with abdominal pain or dysphagia. In the cases reported in the literature, treatment was mostly surgical; there were some reports of minimally invasive transcutaneous or transpapillary procedures and of conservative approaches.
Coronary Disease in Familial Hypercholesterolemia
Authors: JULIUS JENSEN, DAVID H. BLANKENHORN, VALDEMAR KORNERUP
Journal: Circulation (1967)

A report of 20 years' experience with coronary disease in 11 Danish families with hypercholesterolemia and normal serum triglycerides is given. A significantly higher death rate was found in family members who inherited the trait of hypercholesterolemia than in those who did not. The death rate of hypercholesterolemic family members was significantly higher than that found in all other persons of their age and sex living from 1943 to 1964 in Denmark; the death rate for the normocholesterolemic families was not. Most hypercholesterolemic family members died from coronary disease and at an earlier age than is usual for persons with coronary disease in Denmark. There was nothing to indicate that increase in triglycerides rather than increase in cholesterol is related to coronary disease in these families. No environmental factor was found to account for the higher death rate among the members with hypercholesterolemia.
Evidence for a gamma-interferon receptor that regulates macrophage tumoricidal activity.
Authors: A Celada, P W Gray, E Rinderknecht, R D Schreiber
Journal: The Journal of Experimental Medicine (1984)

Gamma-interferon (IFN-gamma) is the macrophage-activating factor (MAF) produced by normal murine splenic cells and the murine T cell hybridoma 24/G1 that induces nonspecific tumoricidal activity in macrophages. Incubation of 24/G1 supernatants diluted to 8.3 IRU IFN-gamma/ml with 6 X 10(6) elicited peritoneal macrophages or bone marrow-derived macrophages for 4 h at 37 degrees C, resulted in removal of 80% of the MAF activity from the lymphokine preparation. Loss of activity appeared to result from absorption and not consumption because (a) 40% of the activity was removed after exposure to macrophage for 30 min at 4 degrees C, (b) no reduction of MAF activity was detected when the 24/G1 supernatant was incubated with macrophage culture supernatants, and (c) macrophage-treated supernatants showed a selective loss of MAF activity but not interleukin 2 (IL-2) activity. Absorption was dependent on the input of either IFN-gamma or macrophages and was time dependent at 37 degrees C but not at 4 degrees C. With four rodent species tested, absorption of murine IFN-gamma displayed species specificity. However, cultured human peripheral blood monocytes and the human histiocytic lymphoma cell line U937 were able to absorb the murine lymphokine. Although the majority of murine cell lines tested absorbed 24/G1 MAF activity, two murine macrophage cell lines, P388D1 and J774, were identified which absorbed significantly reduced amounts of natural IFN-gamma. Purified murine recombinant IFN-gamma was absorbed by elicited macrophages but not by P388D1. Normal macrophages but not P388D1 bound fluoresceinated microspheres coated with recombinant IFN-gamma and binding was inhibited by pretreatment of the normal cells with 24/G1 supernatants. Scatchard plot analysis showed that 12,000 molecules of soluble 125I-recombinant IFN-gamma bound per bone marrow macrophage with a Ka of 0.9 X 10(8) M-1. Binding was quantitatively inhibitable by natural IFN-gamma but not by murine IFN alpha. IFN-beta competed only weakly. Monoclonal antibodies against IFN-gamma either inhibited or enhanced MAF activity by blocking or increasing IFN-gamma binding to macrophages, respectively. These results indicate that IFN-gamma reacts with a receptor on macrophage in a specific and saturable manner and this interaction initiates macrophage activation.
Commentary: Predicting and preventing premature mortality
Authors: D. P Strachan
Journal: BMJ (1996)

Established risk factors for premature mortality may be fixed or modifiable. Prevention in clinical practice naturally concentrates on identifying and attempting to correct modifiable factors such as smoking, hypertension, and hyperlipidaemia. In this context, fixed predictors such as age, sex, and family history of disease may be useful in guiding decisions about whom and when to treat.1 Under the common (but rarely tested) assumption that the relative benefits of treatment are the same for different patient groups, greater absolute benefits may be expected for patients at higher underlying risk of disease. The balance of benefits and side effects may thus depend …
Local diversity of myosin expression in mammalian atrial muscles. Variations depending on age and thyroid state in the rat and the rabbit.
Authors: C A Dechesne, J Léger, P Bouvagnet, H Mairhofer, J J Léger
Journal: Circulation Research (1985)

Rat, rabbit, pig, and bovine atrial myocardia were investigated with anti-alpha and anti-beta myosin heavy chain monoclonal antibodies. Analysis of atrial fibers by indirect immunofluorescence and assay of myosin heavy chains in tissue micro samples by immunoaffinity chromatography revealed both heterogeneity and plasticity in the atrial myosin heavy chains, undetected by electrophoresis of native atrial myosins under nondenaturing conditions. We found both alpha- and beta-like myosin heavy chains to be expressed in rat and rabbit, as they are in pig and bovine, atrial myocardia. They were regionally distributed within atrial muscles. The beta-like myosin heavy chains were present at much lower levels in rat and rabbit atria than in pig and bovine atria. Young rat atrial myosin was composed of only alpha-like heavy chains. In the rat and the rabbit, hyperthyroidism induced a beta- to alpha-like myosin heavy chain transition, which was considerable in the right atria and complete in the left atria. In the rat, thyroidectomy induced a moderate alpha- to beta-like myosin heavy chain transition, visible in the left atria. The significance of this atrial myosin heavy chain polymorphism is discussed in relation to the existence of anatomical localizations of the two myosin variants.
Abstract 1035: Bcl2 is regulated by PKC and Akt and is associated with resistance to cisplatin in endometrial cancer cells.
Authors: Alexandre Rouette, Julie Girouard, Valérie Leblanc, Sophie Parent, Éric Asselin
Journal: Cancer Research (2010)

Abstract Endometrial carcinomas often show resistance to cisplatin. Bcl2 has been shown to be associated with cisplatin resistance in different types of cancers. However, there is no information concerning its possible involvement in chemoresistance and its regulation in endometrial carcinomas. We have tested the ability of cisplatin to induce apoptosis in KLE, a resistant endometrial carcinoma cell line, and examined the putative role for Bcl2 in regulating drug sensitivity. We have investigated the impact of cisplatin treatment on Bcl2 family members and Xiap, an inhibitor of caspase activity. Cisplatin treatment upregulated Bcl2 protein expression in a time-dependant manner in KLE cells, but had no significant impact on the levels of Bax, Bcl-xL and Xiap proteins. As demonstrated by RT-PCR, Bcl2 mRNA was not upregulated in response to cisplatin, suggesting that cisplatin act on Bcl2 expression through a post-translational mechanism. In KLE cells, Bcl2 inhibition by HA14-1 led to increased apoptosis induced by cisplatin. It has been shown that Akt, MAPK and PKC pathways are involved in the regulation of Bcl2 under various conditions and in different cell types. Therefore, KLE cells were treated with inhibitors of MAPK (PD98059) and PKC (CalphostinC) prior to cisplatin treatment. Inhibition of PKC prevented cisplatin-dependant upregulation of Bcl2 protein, while MAPK inhibition had no impact. We previously showed that KLE cell line express high levels of phosphorylated Akt (pAkt) isoforms. Then, KLE cells stably expressing shRNA for all three Akt isoforms were established. Treatment of these cells with cisplatin prevented the increase of Bcl2 expression and led to increased apoptosis by cisplatin. These data suggest a role for Bcl2 in cisplatin resistance in endometrial carcinoma cells. Also, they indicate that PKC and Akt are involved in regulation of Bcl2 expression in this experimental model. 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 1035.
Reply from Authors re: Guido Barbagli, Salvatore Sansalone, Massimo Lazzeri. Oral Mucosa and Urethroplasty: It’s Time to Change. Eur Urol 2012;62:1071–3
Authors: Katja Kero, Jaana Rautava, Kari Syrjänen, Seija Grenman, Stina Syrjänen
Journal: European Urology (2012)
Diagnosis and treatment of scabies.
Authors: A. Lyell
Journal: BMJ (1967)

The diagnosis of scabies depends on finding a burrow or one stage of the parasite. The search is prompted by clinical suspicion and informed by knowledge of the natural history and habits of the human Acarus scabiei. The best source of this information is the monograph by K. Mellanby.1 Scabies should be considered in every patient who complains of persistent itch. In typical cases the diagnosis is easy, but when the visible changes are unusual or slight scabies may not be suspected. It is important to think of the itching patient in relation to his environment, and if another member of the household is itching too there is a prima facie case for suspect ing an infestation.