tbuckley/cabot-search huggingface dataset:
Inducible CD40 expression mediates NF B activation and cytokine secretion in human colonic fibroblasts
Authors: C M Gelbmann, S N Leeb, D Vogl, M Maendel, H Herfarth, J Schölmerich, W Falk, G Rogler
Journal: Gut (2003)

CD40 has been shown to be a functional activation antigen on a variety of cell types involved in immune responses. As intestinal fibroblasts and myofibroblasts may play a role during mucosal inflammation, we investigated the functional consequences of CD40 induction in primary cultures of human colonic fibroblasts.Primary colonic lamina propria fibroblasts (PCLF) were isolated from endoscopic biopsies and surgical specimens. Cultures were used between passages 3 and 9. CD40 surface display was determined by FACS analysis and mRNA expression by reverse transcription-polymerase chain reaction. Secretion of cytokines was determined by ELISA. Nuclear factor kappaB (NFkappaB) activation was shown by electrophoretic mobility shift assay (EMSA).After priming with interferon gamma (IFN-gamma) (200 U/ml) for 72 hours, five of eight tested PCLF cultures showed induction of CD40 surface display (up to 10-fold). Induction of CD40 mRNA expression was demonstrated by semiquantitative polymerase chain reaction. In the responder-PCLF cultures, IFN-gamma alone caused a 1.5-5-fold increase in interleukin (IL)-8 secretion. Addition of 1 ng/ml CD40L was sufficient to achieve a further increase in IL-8, IL-6, or monocyte chemotactic protein 1 (MCP-1) secretion (2.5-18-fold of controls). Incubation with CD40L alone without priming with IFN-gamma had no effect. The proteasome inhibitor N-acetyl-leucinyl-leucinyl-norleucinal (ALLN 100 microM) reduced IFN-gamma/CD40L mediated cytokine induction, suggesting participation of NFkappaB, which was directly demonstrated by EMSA. CD4+ T cells induced MCP-1 secretion by PCLF, which was prevented by addition of an excess of CD40-IgG fusion protein. CD40 expression on PCLF could also be demonstrated in vivo by immunohistochemistry.The CD40-CD40L pathway augments mucosal inflammatory responses via mucosal PCLF. CD40-CD40L mediated T cell/PCLF interactions could play an important role during intestinal mucosal inflammation.
The Conduction System in Acute Myocardial Infarction Complicated by Heart Block
Authors: RICHARD SUTTON, MICHAEL DAVIES
Journal: Circulation (1968)

Detailed histological examination of the conduction system in 29 cases of acute myocardial infarction complicated by heart block has been carried out. In 24 cases posterior infarction was present and occlusion had occurred in the artery from which the blood supply to the A-V node was ultimately derived. In these cases major structural damage to the conduction system was rare, but when present, involved the bundle branches. A-V block in posterior infarction is therefore usually due to hypoxia or other reversible factors rather than structural damage to the conduction system. These findings are consistent with the high incidence of transient heart block in survivors. In five cases anterior infarction alone was present. The blood supply of the A-V node was not compromised, but massive infarction had caused major damage to both bundle branches. Since major structural damage to the conduction system is uncommon in myocardial infarction, only a minority of survivors will have permanent heart block. In those cases in which there is extensive damage to the bundle branches there is a risk of high mortality and permanent block particularly when the infarct is anteroseptal.
Outbreak of Food-poisoning Caused by Salmonella Virchow in Spit-roasted Chicken
Authors: A. B. Semple, G. C. Turner, D. M. O. Lowry
Journal: BMJ (1968)

Salmonella virchow food-poisoning acquired from eating chicken caused illness in at least 50 people who attended a tennis club function in Liverpool, and in many other people in the Merseyside area. In some cases the illness was severe, with positive blood cultures, and 35 people were admitted to hospital. The source of infection was a retail shop which received deep-frozen chickens already contaminated with S. virchow from a packing-station in Cheshire. These chickens were spit-roasted after inadequate thawing and subsequently handled under unhygienic conditions. The result was a massive build-up of salmonella contamination in the shop and in the chicken portions sold. S. virchow was isolated from over 160 patients and contacts in the Merseyside area during the outbreak and many continued to excrete the organism in the faeces after four months. Antibiotic treatment was not recomended because there was no evidence that it shortened the duration of excretion. A high rate of contamination of chickens from a packing-station by a salmonella type capable of causing serious disease in man is clearly a public health problem which cannot be ignored. The use of rotary spits for roasting chickens requires thorough investigation and appraisal, because as operated at present they evidently constitute a public health hazard.
Dissemination of Relevant Information on Hypertension
Authors: Jeoffrey K. Stross
Journal: JAMA (1981)

The timely dissemination of new medical information to the practicing physician has been identified as a problem. To examine the magnitude of this problem and useful strategies for correction, we surveyed primary care physicians to determine their knowledge of the Hypertension Detection and Follow-up Program, a recent clinical trial with important treatment implications. Forty percent of family physicians (44/110) were aware of the study within two months of publication, and 63% of internists (114/182) learned of it within six months. Eighty percent of the family physicians and 50% of the internists listed medicine journals as the source of their knowledge, while 40% of the internists learned of it from continuing medical education (CME) courses. These findings indicate that rapid dissemination of new information can occur when relevant journals are used and that CME courses also provide a timely and effective means of dissemination.
IRRADIATED ERGOSTEROL POISONING
Authors: A. L. Bacharach
Journal: JAMA (1942)

To the Editor:—  Your issue of May 16 has reached me somewhat belatedly, for reasons that need not be elaborated. I note therein a report by Tumulty and Howard on 2 cases of irradiated ergosterol poisoning. It is made quite clear in the text of the paper that the patients were fed mixtures of calciferol, lumisterol, tachysterol and toxisterol, and I cannot see any reason for attributing the intoxication to calciferol rather than to one or other of the nonantirachitic substances. It is perhaps significant that in this country, where irradiated ergosterol went out of use over ten years ago and was entirely replaced by preparations of pure calciferol, there have been no reports of intoxication, though this may have been due to the conservative dosage adopted by the majority of practitioners in this country. Moreover, tachysterol and toxisterol, and possibly one or both of the suprasterols, have a toxic
Cizolirtine Citrate Is Safe and Effective for Treating Urinary Incontinence Secondary to Overactive Bladder: A Phase 2 Proof-of-Concept Study
Authors: František Zát’ura, Jaroslav Všetiča, Montserrat Abadías, Ivan Pavlík, Peter Schraml, Milos Brod’ák, Jesús Villoria, Mariá Sust
Journal: European Urology (2009)
Abstract 5193: Novel candidate oncogenes with mutation hot spots in microsatellite unstable colorectal cancer
Authors: Alexandra E. Gylfe, Sari Tuupanen, Ulrika Hänninen, Johanna Kondelin, Heikki Ristolainen, Riku Katainen, Esa Pitkänen, Minna Taipale, Jussi Taipale, Claus Lindbjerg Andersen, Laura Renkonen-Sinisalo, Heikki Järvinen, Jan Böhm, Jukka-Pekka Mecklin, Pia Vahteristo, Lauri A. Aaltonen
Journal: Cancer Research (2014)

Abstract Around 15% of colorectal cancers (CRCs) show microsatellite instability (MSI). MSI CRCs are prone to repeat mutations due to defective mismatch repair. The high background mutation frequency has discouraged systematic mutations screens in this tumor type. However, these tumors might form a sensitive system for generation and selection of oncogenic mutation hot spots. The aim of this study is to identify novel oncogenes with mutation hot spots that drive MSI CRC tumorigenesis. The exomes of 25 MSI tumors and respective healthy tissues were sequenced as the discovery set. The exome data was searched for mutation hot spots, with recurrent somatic missense mutations in at least two tumors. Potential mutation hot spots were observed in 43 genes and among these were the following known oncogenes: BRAF (V600E), CTNNB1 (T41A) and PIK3CA (H1047R). Novel potential mutation hot spots were identified in 40 genes and these were validated by Sanger sequencing. Mutation hot spots in 33 genes were confirmed and these were further screened in a validation set of 254 MSI CRCs. Fourteen genes displayed hotspot mutations also in the validation set with a total hot spot mutation frequency of 1.1-3.6 %. Many of the validated genes encode for known cancer-related proteins and for proteins with molecular and cellular functions relevant to cancer development and progression. Further work is needed to clarify the functional role of the identified hot spot mutations in MSI CRC tumorigenesis. The novel mutation hotspots may be utilized to develop personalized tumor profiling and therapy. Citation Format: Alexandra E. Gylfe, Sari Tuupanen, Ulrika Hänninen, Johanna Kondelin, Heikki Ristolainen, Riku Katainen, Esa Pitkänen, Minna Taipale, Jussi Taipale, Claus Lindbjerg Andersen, Laura Renkonen-Sinisalo, Heikki Järvinen, Jan Böhm, Jukka-Pekka Mecklin, Pia Vahteristo, Lauri A. Aaltonen. Novel candidate oncogenes with mutation hot spots in microsatellite unstable colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5193. doi:10.1158/1538-7445.AM2014-5193
Reply to Michael Froehner's Letter to the Editor re: Kenneth G. Nepple, Andrew J. Stephenson, Dorina Kallogjeri, et al. Mortality After Prostate Cancer Treatment with Radical Prostatectomy, External-Beam Radiation Therapy, or Brachytherapy in Men Without Comorbidity. Eur Urol 2013;64:372–8
Authors: Kenneth G. Nepple, Adam S. Kibel
Journal: European Urology (2013)
Benign (Favorable) Types of Brain Tumor
Authors: Gilbert Horrax
Journal: New England Journal of Medicine (1954)

IN 1941 a review of a series of 400 verified brain tumors was made, with certain statistics of useful survival of patients who had what were termed favorable tumors.1 This favorable group at that time represented a little more than half (56 per cent) of the whole number of tumors, and it was found in the follow-up studies that 71 per cent of patients with one of these benign new growths had been able to lead useful lives from one to eight years after the removal of the tumors. This review in reality was little more than a preliminary report, . . .
ADVANCED TETANUS CURED BY INTRATHECAL INJECTION OF ANTITOXIN
Authors: B. Muir
Journal: BMJ (1927)

TETANUS CURED BY INTRATHECAL ANTITOXIN.MEDICALJOURNAL C'as 1.--A iman, aged 57, with severe aniaemia, diagnosed as pr'obably perniiicious.The blood count at the commenicemzenit of treatmenit (September 23rd, .1924)was as follows: Red blood corpuscles 2,600,000, wlhite corpuscles 23,000, haemoglobini 46 -per celnt.Coulnts taken at monitlhly intervals sllowed a gradual imn- pro-emenit, anid the last count, taken in April, 1925, sloowed a dlecrease of whlite blood corpuscles to 9,000 per cubic millimetre.The paticnt whleni last seeni seemed practically nlormal.Another t'-vpe is seen in the following (ase. ('.se C.-A man, aged 35, with nieurastlenia of some years' stanidinig.He was melanicholic, had lost Iiis griip oni life, anid had to give up hiis work.He suffered from in)somnia and loss cf miemory.In this case the whole body was treated for three nlinutites every otlher day, gradually increasel to four and a lhalf nmitnutes.Tllere was marked impr ovemeiit at the enll of two weeks.At tlle enid of a month hie was able to take a fresh
A Multicomponent Intervention To Prevent Major Bleeding Complications in Older Patients Receiving Warfarin
Authors: Rebecca J. Beyth
Journal: Annals of Internal Medicine (2000)

Background: Warfarin is effective in the treatment and prevention of many venous thromboembolic disorders, but it often leads to bleeding. Objective: To develop a multicomponent program of management of warfarin therapy and to determine its effect on the frequency of warfarin-related major bleeding in older patients. Design: Randomized, controlled trial. Setting: University hospital in Cleveland, Ohio. Patients: 325 patients 65 years of age or older who started warfarin therapy during hospitalization. Interventions: Patients were stratified according to baseline risk for major bleeding and were randomly assigned to receive the intervention (n = 163) or usual care (n = 162) by their primary physicians for 6 months. The intervention consisted of patient education about warfarin, training to increase patient participation, self-monitoring of prothrombin time, and guideline-based management of warfarin dosing. Measurements: Major bleeding, death, recurrent venous thromboembolism, and therapeutic control of anticoagulant therapy at 6 months. Results: In an intention-to-treat analysis, major bleeding was more common at 6 months in the usual care group than in the intervention group (cumulative incidence, 12% vs. 5.6%; P = 0.0498, log-rank test). The most frequent site of major bleeding in both groups was the gastrointestinal tract. Death and recurrent venous thromboembolism occurred with similar frequency in both groups at 6 months. Throughout 6 months, the proportion of total treatment time during which the international normalized ratio was within the therapeutic range was higher in the intervention group than in the usual care group (56% vs. 32%; P < 0.001). After 6 months, major bleeding occurred with similar frequencies in the intervention and usual care groups. Conclusions: A multicomponent comprehensive program of warfarin management reduced the frequency of major bleeding in older patients. Although the generalizability and cost-effectiveness of this program remain to be demonstrated, these findings support the premise that efforts to reduce the likelihood of major bleeding will lead to safe and effective use of warfarin therapy in older patients.
THE HISTOLOGICAL DISTRIBUTION OF THE BLOOD GROUP SUBSTANCES IN MAN AS DISCLOSED BY IMMUNOFLUORESCENCE
Authors: Aron E. Szulman
Journal: The Journal of Experimental Medicine (1964)

The ABH antigens have been mapped out in the tissues of embryos and fetuses, 18 to 125 mm crown to rump length, 6 to 14(1/2) weeks ovulation age. Both the H and A,B antigens have the same distribution, and their spatial and temporal parallel obtains in intrauterine as well as extrauterine phases of life. The cell wall antigens are present in their maximal distribution in the youngest specimens available. They outline the endothelium of the cardiovascular system, and the cells of most of the epithelia throughout the body. The exceptions are the liver, the adrenal, and the nervous system, presumed to have lost the epithelial antigens at stages antedating the youngest specimens here described. The antigens of the stratified epithelia (and of the simple epithelia of the renal collecting tubules), together with the endothelial antigens, are permanent and persist into and throughout adult life. All other cell wall antigens disappear at a time characteristic for each organ. The antigenic recession coincides with recognizable steps of morphological advancement and often with assumption of function by the organ concerned; it is completed at about the end of the first trimester of pregnancy. The secretion-borne antigens first appear at the 35 to 40 mm stage (8 weeks ovulation age) in the salivary glands and in the stomach, to be followed in a constant sequence by the rest of the gastrointestinal tract, respiratory system, and pancreas. The secretion of these antigens persists throughout life. The early presence and wide distribution of the cell wall A,B antigens render them likely potential targets for maternal anti-A,B antibodies in heterologous pregnancies; the advent of the water-soluble substances at 8 weeks ovulation age may be providing a buffer shielding the fetal cell wall antigens by mopping up the maternal isoagglutinins.
Abstract 3253: Genetic loci that contribute to aristolochic acid nephropathy and associated upper urothelial cancer
Authors: Thomas A. Rosenquist, Penelope Strockbine, Arthur P. Grollman
Journal: Cancer Research (2010)

Abstract Aristolochic acids (AA) are nitrophenanthrene carboxylic acids found in all Aristolochia species which have been used historically as herbal remedies throughout the world. AA are the suspected causative agent for aristolochic acid nephropathy (AAN), Balkan Endemic Nephropathy (BEN), and so-called Chinese Herb Nephropathy (CHN). Hallmarks of these disease entities are proximal tubule damage and interstitial fibrosis leading to end stage renal disease. At least half of all patients also develop cancers of the upper urothelial tract (UUC). Aristolochic acid-DNA adducts generate signature A:T-&amp;gt;T:A transversions in TP53. Such mutations are rare in sporadic urothelial cancers but predominate in UUC from patients with BEN/AAN/CHN. We have developed a mouse model for AAN that has enabled us to screen for quantitative trait loci (QTL) that increase the susceptibility to AA in mice. Two hundred F2 mice obtained by breeding C57Bl/6J (an AAN-resistant strain) and DBA/2J (an AAN-sensitive strain) were treated with a single dose of AA. Four days later urine was analyzed for markers of kidney function. Mice were then euthanized and tissues were collected for histology and DNA was isolated for analysis of AA-DNA adducts and genotyping. Four QTL were identified; a major QTL, Aanq1(Chr4, 46-71MB), a pair of interacting QTL, Aanq2(Chr3, 116-128MB), and Aanq3 (Chr9, 113-122MB), and a minor QTL that acts additively with Aanq1, Aanq4(Chr6, 124-135MB). Further analyses of the QTL regions and their human orthologs will be presented. The project described was supported by Award Number P01ES004068 from the National Institute of Environmental Health Sciences. 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 3253.
Differential effects of two lots of aroclor 1254: congener-specific analysis and neurochemical end points.
Authors: P R Kodavanti, N Kannan, N Yamashita, E C Derr-Yellin, T R Ward, D E Burgin, H A Tilson, L S Birnbaum
Journal: Environmental Health Perspectives (2001)

Aroclor 1254 is a widely studied commercial polychlorinated biphenyl (PCB) mixture which, by definition, contains 54% chlorine by weight. Recent reports indicate substantial differences in the congener composition among Aroclor lots and hence their biologic effects. We designed the current study to compare the effects of two lots of Aroclor 1254 (lots 6024 and 124-191). We analyzed these two lots for PCB congeners, polychlorinated dibenzofurans (PCDFs), polychlorinated naphthalenes (PCNs), and polychlorinated dibenzodioxins (PCDDs). We used previously established techniques for analyzing intracellular Ca(2+) buffering and protein kinase C (PKC) translocation to test their biologic activity in neuronal preparations. PCB congener-specific analysis indicated that ortho and non-ortho congeners in these two lots varied in their percent contribution. Among all congeners, the percentages of non-ortho congeners (PCBs 77, 81, 126, and 169) were higher in lot 6024 (2.9% of total) than in lot 124-191 (0.02% of total). We detected no dioxins in these two lots (< 2 ppb). Although there are some differences in the congener composition, total PCNs were similar in both lots: 171 ppm in lot 6024 and 155 ppm in lot 124-191. However, total PCDFs were higher in lot 6024 (38.7 ppm) than in lot 124-191 (11.3 ppm). When we tested these two Aroclors on Ca(2+) buffering and PKC translocation in brain preparations, the effects were significantly different. Although lot 124-191 was more potent on PKC translocation than lot 6024, lot 6024 was slightly more active on Ca(2+) buffering than lot 124-191. These effects could not be attributed to the differences in the percentage of non-ortho congeners or PCDFs because they were inactive on these two parameters. The effects could not be attributed to PCNs because the levels were almost similar. The effects seen with two lots of Aroclor 1254 in neuronal cells were also not predicted based on the TCDD toxic equivalents (TEQs), although TEQs predicted the effects on ethoxyresorufin-O-deethylase (EROD) or methoxyresorufin-O-deethylase (MROD) activities. It is possible that the differential effects seen in neuronal cells could be caused by differences in the composition of ortho-congeners in these two mixtures, because PCBs with ortho-lateral substitutions can exhibit different activities on the selected neurochemical end points. Because of these differential effects with different lot numbers, the composition of Aroclor mixtures used in investigations should be disclosed.