tbuckley/cabot-search huggingface dataset:
Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria
Authors: Yuumi Nakamura, Naotomo Kambe, Megumu Saito, Ryuta Nishikomori, Yun-Gi Kim, Makoto Murakami, Gabriel Núñez, Hiroyuki Matsue
Journal: The Journal of Experimental Medicine (2009)

Urticarial rash observed in cryopyrin-associated periodic syndrome (CAPS) caused by nucleotide-binding oligomerization domain–leucine-rich repeats containing pyrin domain 3 (NLRP3) mutations is effectively suppressed by anti–interleukin (IL)-1 treatment, suggesting a pathophysiological role of IL-1β in the skin. However, the cellular mechanisms regulating IL-1β production in the skin of CAPS patients remain unclear. We identified mast cells (MCs) as the main cell population responsible for IL-1β production in the skin of CAPS patients. Unlike normal MCs that required stimulation with proinflammatory stimuli for IL-1β production, resident MCs from CAPS patients constitutively produced IL-1β. Primary MCs expressed inflammasome components and secreted IL-1β via NLRP3 and apoptosis-associated speck-like protein containing a caspase recruitment domain when stimulated with microbial stimuli known to activate caspase-1. Furthermore, MCs expressing disease-associated but not wild-type NLRP3 secreted IL-1β and induced neutrophil migration and vascular leakage, the histological hallmarks of urticarial rash, when transplanted into mouse skin. Our findings implicate MCs as IL-1β producers in the skin and mediators of histamine-independent urticaria through the NLRP3 inflammasome.
Inhibition of pinacidil induced IK(ATP) in heart by changes in extracellular pH
Authors: W.-M. Kwok, R. S Kass
Journal: Cardiovascular Research (1994)

Objective: The aim was to determine whether extracellular protons influence the activation of ATP sensitive potassium channels (KATP) in heart by the drug pinacidil. Methods: Single channel and whole cell currents were measured in enzymatically dispersed guinea pig ventricular myocytes with patch clamp procedures. ATP sensitive potassium channel activity was induced by pinacidil in whole cell experiments and either by lowering cytoplasmic ATP or pinacidil in membrane patch experiments. Results: Extracellular acidification inhibited and extracellular alkalisation potentiated ATP sensitive potassium channel currents (IK(ATP) induced by pinacidil under whole cell conditions. In membrane patches. IK(ATP) induced by low cytoplasmic ATP (1 mM) was not sensitive to changes in extracellular pH, but IK(ATP) induced by cytoplasmic application of pinacidil was inhibited by extracellular acidification. Conclusions: Interactions between protons and pinacidil drug molecules underlie the pH dependent changes in IK(ATP) induced by pinacidil. Based on the kinetics of pH dependent changes in pinacidil induced channel activity in inside-out membrane patches, our data suggest that the important inhibitory site of action of this drug is located on the extracellular side of the cell membrane. Cardiovascular Research 1994:28:836-840
Sampling methods III
Authors: P. Sedgwick
Journal: BMJ (2011)

A randomised controlled trial investigated whether physical activity in preschool children (under 5 years) reduced obesity. The active intervention was an enhanced physical activity programme plus health education, whereas the control treatment was no intervention. All preschool nurseries in Glasgow were invited to participate.1

Each nursery was categorised by three characteristics thought to affect the intervention and the study outcomes. These characteristics were type of nursery (school, class, extended day, private sector), size of nursery (area and number of children), and socioeconomic status of the area. For each set of preschool nurseries with the same characteristics, two were randomly selected from those that agreed to participate, one of which was randomly allocated to active intervention and the other to control. In total, the trial investigated 36 preschool nurseries. …
Effects of inosine on glycolysis and contracture during myocardial ischemia.
Authors: E D Lewandowski, D L Johnston, R Roberts
Journal: Circulation Research (1991)

The effects of inosine (INO) on substrate metabolism and rigor formation in ischemic myocardium were examined in isolated rabbit hearts. Metabolite content was assessed in tissue extracts by chemical analysis and in the whole heart by 13C and 31P nuclear magnetic resonance spectroscopy. In ischemic hearts metabolizing either [3-13C]pyruvate or [1-13C]glucose, 1 mM INO increased both total and 13C-labeled alanine content; lactate content was unaffected. At 3 minutes of ischemia, tissue alanine was 1.81 +/- 0.11 microM/g wet wt (mean +/- SEM) in hearts perfused with pyruvate+INO versus 1.23 +/- 0.15 microM/g wet wt in hearts perfused with pyruvate alone (p less than 0.05). INO reduced tissue glycogen during ischemia in pyruvate-perfused hearts. Tissue alanine content in ischemic hearts that were supplied glucose+INO (1.29 +/- 0.13 microM/g wet wt) was greater than in ischemic hearts supplied glucose alone (0.65 +/- 0.14 microM/g wet wt). Alanine was found to originate from pyruvate and was a glycolytic end product in glucose-perfused hearts. INO raised the [3-13C]alanine/[3-13C]lactate ratio in ischemic, intact hearts (glucose = 0.24 +/- 0.07 versus glucose+INO = 0.60 +/- 0.09; pyruvate = 0.49 +/- 0.08 versus pyruvate+INO = 0.89 +/- 0.08). At 7 minutes of ischemia, ATP content fell to 70 +/- 3% with glucose+INO versus 58 +/- 5% with glucose alone. Rigor (stone heart) was delayed from 14.7 +/- 1.3 to 23.2 +/- 1.6 minutes with INO. INO did not change ATP content in ischemic hearts that were supplied pyruvate but delayed rigor (pyruvate = 9.9 +/- 1.2 minutes; pyruvate+INO = 15.6 +/- 1.0 minutes), possibly at the expense of glycogen. Supplemental glucose improved the effectiveness of INO with pyruvate to preserve ATP (pyruvate+glucose = 42 +/- 6%; pyruvate+glucose+INO = 72 +/- 6%) and further delayed rigor (pyruvate+glucose = 13.3 +/- 1.5 minutes; pyruvate+glucose+INO = 20.3 +/- 1.8 minutes). Glucose metabolism supported improved energetic and contractile states in ischemic hearts treated with INO. Thus, cardioprotection of the ischemic heart by INO was associated with preservation of functional integrity and improved energy production due to increased glycolytic activity. Activation of glycolysis in the presence of INO was accommodated by augmented alanine production without the additional accumulation of lactate.
Histopathologic analysis of transjugular intrahepatic portosystemic shunts
Authors: H Ducoin, J El-Khoury, H Rousseau, K Barange, J Peron, M Pierragi, J Rumeau, J Pascal, J Vinel, F Joffre
Journal: Hepatology (1997)

This prospective study was undertaken in 17 patients treated with 22 transjugular intrahepatic portosystemic shunt (TIPS) procedures and aimed to evaluate the nature and causes of short- and long-term shunt abnormalities. Specimens were collected after autopsy in 6 patients and after liver transplantation in 11 patients; the time from shunting ranging from 4 to 385 days. During the first 2 weeks the shunt surface was covered by poorly organized fibrin platelet clots that were mixed with inflammatory and red blood cells. Thereafter, a pseudointima developed, initially made of loose granulation tissue that was formed by edema, myofibroblasts, neo-capillaries, collagen fibers, and inflammatory cells. This pseudo-intima extended with time as the myofibroblasts increased in number, as the collagen fibers thickened, and as the inflammatory cells grew more scarce. Its thickness ranged from 50 to 3,500 microm, the maximal values being observed in the middle of the shunt. The shunt was obstructed by a clot in 4 patients (18%). In 7 shunts (31.8%) the pseudo-intima was thicker than 1,000 microm and was referred to as hyperplastic pseudo-intima. It showed more dense inflammatory infiltrate and anarchic deposition of more scarce collagen fibers. Pseudo-intima hyperplasia was associated with previously diagnosed thrombosis, which had been treated by dilatation in 2 cases and by biliary deposits in 3 cases, while it remained unexplained in 2 cases. Accordingly, this study confirms the following: 1) that early TIPS obstruction results from thrombosis; 2) that 2 weeks after insertion, the stent is covered by a smooth pseudo-intima; 3) that thereafter, pseudo-intimal hyperplasia is the main cause of TIPS stenosis or occlusion; and 4) that biliary secretions and previous thrombosis could be important triggering mechanisms for this pseudo-intima overgrowth.
Immunoelectronmicroscopic examination of early lesions in histamine induced immune complex vasculitis in man
Authors: HELMUT H. WOLFF, W. MACIEJEWSKI, R. SCHERER, O. BRAUN-FALCO
Journal: British Journal of Dermatology (1978)

In 4 cases of allergic vasculitis circulating immune complexes (IC) were demonstrated. Spontaneous and histamine induced vascular changes were studied by immunofluorescence microscopy. The early events in IC vasculitis were investigated at the ultrastructural level by immunoelectronmicroscopy using the peroxidase-antiperoxidase multistep technique. Our findings support the concept that human IC vasculitis is triggered by the deposition of circulating IC in the walls of postcapillary venules between endothelial cells, pericytes and the layers of the basal lamina. Tissue destruction is only secondary due to local complement activation and the release of lysosomal enzymes from chemotactically attracted leukocytes.
Abstract 1519: Identification and functional analysis of genes involved in cholesterol metabolism that are upregulated in prostate cancer stroma.
Authors: Shingo Ashida, Chiaki Kawada, Keiji Inoue, Taro Shuin
Journal: Cancer Research (2013)

Abstract Recent studies have highlighted tumor microenvironment as important in carcinogenesis and progression. Especially in prostate cancer (PC), it has been suggested that tumor microenvironment plays an important role in progression, acquisition of androgen independence, and distant metastasis. However, little is known about the genetic basis of human PC microenvironment. To clarify the mechanism of PC progression and metastasis, we investigated cross-interaction of PC epithelial cells and stromal cells by analyzing genome-wide gene expression profiles. We hypothesized that PC cells could affect on stromal cells to change their characteristics into so-called cancer-associated fibroblasts (CAFs), which might contribute to cancer invasion and metastasis. We identified genes that were up-regulated in PC stroma by analyzing gene expression profiles of normal human prostate stromal cells (PrSC) co-cultured with human PC cells (LNCaP), which included some genes involved in cholesterol metabolism, such as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). HMGCR is the rate-limiting enzyme for cholesterol synthesis and the pharmalogical target for statins. We confirmed the overexpression of HMGCR in PC stroma by immunohistochemistry. Then we knocked down endogenous HMGCR in PC cells by small interfering RNA, which resulted in the significant reduction of PC cell viability. In contrast, HMGCR overexpression stimulated PC cell growth. These results provide clues to the molecular mechanisms underlying PC invasion and metastasis, and suggest candidate genes the products of which might serve as molecular targets for the treatment of PC. Citation Format: Shingo Ashida, Chiaki Kawada, Keiji Inoue, Taro Shuin. Identification and functional analysis of genes involved in cholesterol metabolism that are upregulated in prostate cancer stroma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1519. doi:10.1158/1538-7445.AM2013-1519
Unexpected Demonstration of Superior Vena Caval Obstruction in Third Trimester Lung Imaging
Authors: BEVERLY A. TROMBLEY, CAROL S. MARCUS, TIMOTHY KOCI
Journal: Clinical Nuclear Medicine (1988)

A large focus of liver activity was seen after the injection of Tc-99m macroaggregated albumin (MAA) in a pregnant patient thought to have pulmonary embolism (PE). The correct diagnosis of superior vena caval (SVC) obstruction led to an immediate cesarian section, CT of the chest and abdomen, open lung biopsy of a mediastinal mass, and radiation therapy for the lymphoma with pericardial invasion, all within 24 hours of presentation. The next day, an in vitro labeled Tc-99m red blood cell (RBC) angiogram was performed, which documented collateral flow from the SVC obstruction to the abdomen and filling of the right ventricle via the liver, presumably through reopened channels of the umbilical vein.
Study busts myth of "metabolically healthy" obesity
Authors: S. Mayor
Journal: BMJ (2013)

Obese people are at a greater risk of death and cardiovascular events even without metabolic abnormalities than people in the normal weight range, warns a study that questions the belief that it’s possible to be healthy despite being seriously overweight.1

The systematic review and meta-analysis included observational studies published between 1950 and 2013 that evaluated mortality from all causes or cardiovascular events by body mass index and metabolic status, defined by components of the metabolic syndrome such as glucose tolerance and …
Massive haemoptysis as the presenting symptom in mitral stenosis.
Authors: A Scarlat, G Bodner, M Liron
Journal: Thorax (1986)

Mitral stenosis is a well known cause of haemoptysis, but a severe, sudden pulmonary haemorrhage is a rare presenting symptom in a hitherto symptom free person. Case reportA 25 year old man had no prior symptoms and had been engaged in sport until a week before admission to hospital, when he had a "mild cold" with cough and one episode of chills.On the day of admission, after coitus, he had suddenly started to cough and expectorated large amounts of blood.On admission to hospital he was severely dyspnoeic and during three hours he expectorated about 1000 ml of bright red blood without clots.The blood pressure was 120/70 mm Hg, pulse rate 120/min, and respiratory rate 50/min.The rectal temperature was 39.5 C. The apex beat was normal in location but accentuated.No cardiac murmurs were found.Crackles and wheezes were heard over the lower halves of both lungs.The rest of the physical examination revealed no abnormality.The haemoglobin was 10.4 g/dl with 18 x I09 leucocytes/l.Arterial blood analysis showed a mild respiratory alkalosis (pH 7.44, oxygen tension 86 mm Hg (l1.5 kPa), carbon dioxide tension 29 mm Hg (3.9 kPa)).Sputum obtained after the haemoptysis had ceased showed Gram positive cocci and leucocytes on microscopic exam- ination.Sputum cultures yielded mixed normal flora.Blood cultures examined later were negative.The electro- cardiogram showed sinus tachycardia with incomplete right bundle branch block and a QRS axis of + 1100.The P waves
Gonococcal Proctitis in a Married Woman
Authors: Nicholas J. Fiumara
Journal: JAMA (1977)

ABOUT 3 million persons in this country acquire gonorrhea each year, according to the US Public Health Service. Many writers have called attention to the increasing problem of gonococcal proctitis in women, especially in those who have cervical gonorrhea.<sup>1-3</sup>The sexual gymnastics of contemporary society make it mandatory for physicians to be aware not only of the many routes of infection, but also of the probable sites involved. <h3>Report of a Case</h3> One Monday morning, an internist from a local hospital asked me to see a married couple whom he had treated for gonorrhea two months earlier. The husband had a recurrence of a purulent urethral discharge and a positive gonococcal smear. He denied vehemently any extramarital exposures. The wife, whom the physician had not examined that morning, just as vehemently protested her innocence. The couple insisted that the discharge could not be of a gonococcal nature, and if
Screening for Sickle-cell Disease
Authors: F. F. Casale
Journal: BMJ (1974)

SIR,-Your leading article (21 September, p. 701) highlights the problems of Negro patients who may have repeated screening tests for sickle-cell disease.Now that the existence of sickle-cell disease in Britain has been recognized and well publicized I feel that the need for screening should be put in the right per- spective on a par with other potentially dangerous problems associated with anaes- thesia and surgery.It is advisable to perform routine screening for haemoglobinopathies on hospital attendance, but should the absence of a sickle-cell test in fit and nonanaemic adults and older children of possible Negro descent be a contraindication to general anaesthesia?This is certainly not the practice anywhere in Africa.The sutgestion that medical cards be carried by these patients is the obvious solution, but logically medical cards should be advisable for most patients and should include not only haemoglobinopathies but other relevant information, such as blood group, drug allergy, therapy with steroids, anticoagulants, etc. for the same reasons as suggesved in the article.
Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow)
Authors: Antonio P. Beltrami, Daniela Cesselli, Natascha Bergamin, Patrizia Marcon, Silvia Rigo, Elisa Puppato, Federica D'Aurizio, Roberto Verardo, Silvano Piazza, Angela Pignatelli, Alessandra Poz, Umberto Baccarani, Daniela Damiani, Renato Fanin, Laura Mariuzzi, Nicoletta Finato, Paola Masolini, Silvia Burelli, Ottorino Belluzzi, Claudio Schneider, Carlo A. Beltrami
Journal: Blood (2007)
3D Porous Chitosan–Alginate Scaffolds: A New Matrix for Studying Prostate Cancer Cell–Lymphocyte Interactions In Vitro
Authors: Stephen J. Florczyk, Gang Liu, Forrest M. Kievit, Allison M. Lewis, Jennifer D. Wu, Miqin Zhang
Journal: Advanced Healthcare Materials (2012)

Abstract The treatment of castration‐resistant prostate cancer (CRPC) remains palliative. Immunotherapy offers a potentially effective therapy for CRPC; however, its advancement into the clinic has been slow, in part because of the lack of representative in vitro tumor models that resemble the in vivo tumor microenvironment for studying interactions of CRPC cells with immune cells and other potential therapeutics. This study evaluates the use of 3D porous chitosan–alginate (CA) scaffolds for culturing human prostate cancer (PCa) cells and studying tumor cell interaction with human peripheral blood lymphocytes (PBLs) ex vivo. CA scaffolds and Matrigel matrix samples support in vitro tumor spheroid formation over 15 d of culture, and CA scaffolds support live‐cell fluorescence imaging with confocal microscopy using stably transfected PCa cells for 55 d. PCa cells grown in Matrigel matrix and CA scaffolds for 15 d are co‐cultured with PBLs for 2 and 6 d in vitro and evaluated with scanning electron microscopy (SEM), immunohistochemistry (IHC), and flow cytometry. Both the Matrigel matrix and CA scaffolds support interaction of PBLs with PCa tumors, with CA scaffolds providing a more robust platform for subsequent analyses. This study demonstrates the use of 3D natural polymer scaffolds as a tissue culture model for supporting long‐term analysis of interaction of prostate cancer tumor cells with immune cells, providing an in vitro platform for rapid immunotherapy development.
Abstract 3522: A Phase 0 microdosing trial to identify chemoresistance: From bench to bedside
Authors: Sisi Wang, Miaoling He, Tao Li, Ralph de Vere White, Primo N. Lara, David Gandara, Philip C. Mack, Kenneth Turteltaub, Paul T. Henderson, Chong-xian Pan
Journal: Cancer Research (2010)

Abstract BACKGROUND: DNA damage is the critical step in cancer cell response to platinum (Pt) chemotherapy. We hypothesize that low levels of Pt-induced DNA damage are predictive of chemoresistance. Accelerator mass spectrometry (AMS) is an ultrasensitive method for measuring radiocarbon. By measuring 14C bound to DNA, AMS can detect carboplatin-induced DNA damage after patients receive one subtoxic microdose of 14C-labeled carboplatin. METHODS: Cancer cells and mice bearing tumor xenografts were treated with one microdose (1/100th of the therapeutic dose) or one therapeutic dose of [14C]carboplatin. Carboplatin-DNA adducts and other relevant parameters such as drug influx/efflux, intracellular drug inactivation, and repair of DNA damage, were measured and correlated with response to chemotherapy. RESULTS: AMS detected Pt-DNA damage when cancer cells and mice with tumor xenografts were exposed to one subtoxic microdose of [14C]carboplatin. The levels of microdose-induced DNA damage were linearly proportional to the DNA damage caused by the therapeutic drug dose (R2=0.92, p&amp;lt;0.001); and these levels of DNA damage correlated with chemoresistance. Low DNA damage predicts chemoresistance. Measuring drug uptake/efflux, intracellular inactivation and DNA repair allowed insight into some resistance mechanisms. A Phase 0 microdosing trial has been designed to study patients with non-small cell lung cancer or bladder cancer who are scheduled to receive Pt-based chemotherapy. One subtoxic microdose of 14C-carboplatin will be administered to these patients before biopsy. Pt-induced DNA damage and repair in left-over tumor biopsy specimens and other relevant parameters will be measured and correlated with the response and toxicity of chemotherapy. Molecular analysis of genes such as ERCC1 and RRM1 will be analyzed and compared with this Phase 0 results. CONCLUSION: The levels of DNA damage induced by nontoxic microdosing carboplatin can potentially predict chemoresistance in patients. A phase 0 microdosing trial is under the IRB review to identify chemoresistance and determine the underlying resistant mechanisms for personalized therapy before patients receive toxic Pt chemotherapy. 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 3522.
Ebun Willie Robert Gorham Priddy
Authors: E. Luke
Journal: BMJ (2003)

Former consultant obstetrician and gynaecologist Freetown, Sierra Leone (b Victoria, Cameroon, 1926; q Leeds 1956; FRCOG, FWACS), died from carcinomatosis following stomach cancer on 25 August 2003.​2003.




Figure 1




Bill Priddy won a prestigious state scholarship to study medicine at Leeds University. Following his house jobs he returned to Freetown in 1965 as medical superintendent in charge of Bo Government Hospital, the second largest in Sierra Leone. In 1967 he obtained the MRCOG in Leeds. On his return to Freetown he was appointed specialist in obstetrics and gynaecology and a tutor in the Department of Clinical Studies, Connaught Hospital, Freetown. The apogee of his career was his appointment as consultant in obstetrics and gynaecology to the Ministry of Health, Sierra Leone. Predeceased by his wife, Betty, he leaves his second wife, Sento; five children; and 11 grandchildren.