tbuckley/cabot-search huggingface dataset:
Gene Transfer of p53 to Arthritic Joints Stimulates Synovial Apoptosis and Inhibits Inflammation
Authors: Qingping Yao, Sujing Wang, Joseph C. Glorioso, Christopher H. Evans, Paul D. Robbins, Steven C. Ghivizzani, Thomas J. Oligino
Journal: Molecular Therapy (2001)

Rheumatoid arthritis (RA) is an autoimmune disease that primarily affects joints. During the pathogenesis of rheumatoid arthritis, the synovial lining becomes dramatically thickened and hyperplastic. This highly aggressive tissue invades and destroys articular cartilage and bone. Several lines of evidence suggest that the proliferation of the synovial tissue may be due to disruption in the control of the cell cycle or apoptotic pathways. In particular, mutations in the tumor suppressor protein p53 have been found in synovial tissue from RA joints. We have examined the effects of overexpression of p53 by adenoviral infection in synovial cells in culture and in synovial tissue in vivo in a rabbit model of arthritis. Here we demonstrate that p53 overexpression resulted in significant apoptosis in human and rabbit synovial cells in culture. Furthermore, intraarticular injection of Ad-p53 resulted in extensive and rapid induction of synovial apoptosis in the rabbit knee without affecting cartilage metabolism. Interestingly, a significant reduction in the leukocytic infiltrate was observed within 24 h postinfection of Ad.p53. These results suggest that intraarticular gene transfer of p53 is able to induce synovial apoptosis as well as reduce inflammation and thus may be useful clinically for the treatment of RA.
Delay in Conception for Former 'Pill' Users
Authors: Shai Linn
Journal: JAMA (1982)

Interview data from 3,214 married women having planned pregnancies and singleton deliveries who had no history of fertility treatment and who conceived more than two weeks after cessation of contraception were analyzed. The interval from cessation of contraception to conception was 13 months or greater for 24.8% of prior "pill" users vs 10.6% for former users of all other methods. As compared with former users of other methods, pill users had a notably lower monthly percentage of conceptions for the first three months and somewhat lower percentage from four to ten months. Results were not altered when potential confounding variables were controlled by logistic regression. At least 15 months of unsuccessful trials might be a more appropriate working definition of infertility for previous pill users rather than the 12-month interval generally accepted for this purpose. (<i>JAMA</i>1982;247:629-632)
Tuberculosis among Vietnamese refugees
Authors: S J Phillips
Journal: BMJ (1981)

interesting to know the results.Two points about tuberculosis in Indochinese refugees are worth noting.Experience with Vietnamese refugees in the United States' shows that the infection rate for tuberculosis is exceedingly high.The overall incidence of tuberculosis among the population of Louisiana in 1979 was 16 per 100 000 (ranging from 5/100 000 for white females to 43/100 000 for black males).In a study of 99 321 refugees from Indochina the incidence of tuberculosis was 926/100 000.In another study' of 86 548 Vietnamese refugees 50%/, had positive Mantoux tests, 2975 had active tuberculosis, and 1897 had inactive tuberculo- sis according to chest x-ray examination and sputum examination.The second point to note is that the Myco- bacterium tuberculosis organisms isolated from Vietnamese refugee immigrants showed a very high incidence of resistance to the common anti-tuberculosis drugs.In a study by Byrd et al on tuberculosis in immigrants2 from Korea, Thailand, Japan and the Philippines, Vietnam, and China, the overall incidence of resistance to isoniazid was 58 0, to streptomycin 360), and to p-aminosalicylic acid 14%,, multiple resistance occurring in 36%' of isolates.Those organisms isolated from the Vietnamese showed a still worse pattern of resistance: only 170% of organisms were fully sensitive and 33 0 showed multiple resistance.The figures for resistance to individual drugs were: isoniazid-50 0,) streptomycin-67%, p-aminosalicylic acid-170o.No organisms isolated from the Vietnamese were resistant to either rifampin or ethambutol.
ENZYMES OF THE GLYCOLYTIC PATHWAY IN SKIN..
Authors: P. D. MIER, D. W. K. COTTON
Journal: British Journal of Dermatology (1967)

Journal Article ENZYMES OF THE GLYCOLYTIC PATHWAY IN SKIN.: III. Phosphorylase Get access P. D. MIER, P. D. MIER The Institute of Dermatology. St. John's Hospital for Diseases of the Skin, Homerton Grove, London. E.9 Search for other works by this author on: Oxford Academic Google Scholar D. W. K. COTTON D. W. K. COTTON The Institute of Dermatology. St. John's Hospital for Diseases of the Skin, Homerton Grove, London. E.9 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 79, Issue 3, 1 March 1967, Pages 164–169, https://doi.org/10.1111/j.1365-2133.1967.tb15826.x Published: 01 March 1967
Mechanism of mammalian cell lysis mediated by peptide defensins. Evidence for an initial alteration of the plasma membrane.
Authors: A Lichtenstein
Journal: Journal of Clinical Investigation (1991)

Defensins induce ion channels in model lipid bilayers and permeabilize the membranes of Escherichia coli. We investigated whether similar membrane-active events occur during defensin-mediated cytolysis of tumor cells. Although defensin-treated K562 targets did not release chromium-labeled cytoplasmic components for 5-6 h, they experienced a rapid collapse (within minutes) of the membrane potential, efflux of rubidium, and influx of trypan blue. Defensin treatment also blunted the subsequent acidification response induced by nigericin, thereby further supporting the notion of enhanced transmembrane ion flow during exposure. These initial effects on the plasma membrane were not sufficient for subsequent lysis; a second phase of injury was required which involved the continued presence of defensin. The rapid membrane permeabilization phase was inhibited by azide/2-deoxyglucose, cytochalasin B, and increased concentrations of extracellular potassium and was unaffected by actinomycin-D, cycloheximide, and varying the calcium concentration. In contrast, the second phase was unaffected by cytochalasin B, inhibited by azide/2-deoxyglucose, enhanced by actinomycin D and cycloheximide, and varied with calcium concentration. These results indicate the initial adverse effect of defensins on mammalian cells occurs at the cell membrane. It is possible that the second phase of injury is mediated intracellularly by defensin that has been internalized through this leaky membrane.
T-cell–restricted T-bet overexpression induces aberrant hematopoiesis of myeloid cells and impairs function of macrophages in the lung
Authors: Shoichi Iriguchi, Norihiro Kikuchi, Shin Kaneko, Emiko Noguchi, Yuko Morishima, Masashi Matsuyama, Keigyou Yoh, Satoru Takahashi, Hiromitsu Nakauchi, Yukio Ishii
Journal: Blood (2014)
<i>Pten</i> Deficiency Activates Distinct Downstream Signaling Pathways in a Tissue-Specific Manner
Authors: Lina I. Yoo, David W. Liu, Sandrine Le Vu, Roderick T. Bronson, Hong Wu, Junying Yuan
Journal: Cancer Research (2006)

PTEN deficiency predisposes to a subset of human cancers, but the mechanism that underlies such selectivity is unknown. We have generated a mouse line that conditionally deletes Pten in urogenital epithelium. These mice develop carcinomas at high frequency in the prostate but at relatively low frequency in the bladder, despite early and complete penetrance of hyperplasia in both organs. Cell proliferation is initially high in the bladder of newborn Pten-deficient mice but within days is inhibited by p21 induction. In contrast, proliferation remains elevated in Pten-deficient prostate, where p21 is never induced, suggesting that p21 induction is a bladder-specific compensatory mechanism to inhibit proliferation caused by Pten deletion. Furthermore, the AKT/mammalian target of rapamycin growth pathway, which is highly activated in Pten-deficient prostate, is not activated in bladder epithelium. Our results reveal alternative downstream signaling pathways activated by Pten deficiency that lead to tissue-specific susceptibilities to tumorigenesis.
Seroma formation after breast cancer surgery and its risk factors.
Authors: Y Lin, W Yin, L Zhou, J Lu, G Di, J Wu, Z Shen, Z Shao
Journal: Cancer Research (2009)

Abstract Abstract #4085 Background:. Seroma formation is one of the most common complications after breast cancer surgery including modified radical mastectomy and breast conservative surgery. Our study aims to investigate the risk factors of postoperative seroma in Chinese breast cancer patients.&amp;#x2028; Methods: Clinical data of 158 women who underwent surgerical therapy for breast cancer in our hospital were collected prospectively and all patients were followed up. The risk factors for seroma occurrence were compared between the seroma group and control group using X 2 test or t test, as well as the logistic regression was used as multivariate analysis.&amp;#x2028; Results: Univariate analysis showed that the average age of the seroma group was significantly higher than those without seroma formation(58.71vs51.00, P=0.0019), but the total serum protein and albumin content were lower (68.47g/L vs 72.53g/L, P=0.009 and 40.75g/L vs 42.52g/L,P=0.020, respectively). In seroma group, the drainage volume of the first three days, the total and daily drainage volume were all higher (all p values less than 0.01), as well as drainage duration and hospital stay were longer(8.3d vs 14.4d, P=0.000 and 11.5d vs 23.7d, P=0.000, respectively). Logistic regression showed that older patients (OR=1.080, 95%CI 1.016∼1.148, P=0.013), lower total serum protein content(OR=0.814, 95%CI 0.705∼0.940, P=0.005)and higher drainage volume in d1(OR=1.009, 95%CI 1.001∼1.016, P=0.022) and d3 (OR=1.017, 95%CI 1.005∼1.029, P=0.005) were all independent risk factors for subcutaneous seroma. The daily average drainage curve showed a gradually decreasing trend with a highest collections in the first three days. The seroma group had significantly higher average daily drainage volume( P=0.034) and longer duration (P=0.000).&amp;#x2028; Conclusion:The risk factors of seroma formation after breast cancer surgery are complicated. However in order to prevent its occurrence effectively, the factors including age, nutrition status and daily drainage volume should be taken into consideration. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4085.
Endothelin B receptor–Mediated protection against anoxia-reoxygenation injury in perfused rat liver: Nitric oxide–Dependent and –Independent mechanisms
Authors: Hisashi Taniai, Makoto Suematsu, Tsuneharu Suzuki, Shinji Norimizu, Rio Hori, Yuzuru Ishimura, Yuji Nimura
Journal: Hepatology (2001)

This study aimed to investigate the roles of endothelin (ET) receptors in biliary dysfunction and cell injury in postischemic livers. Rat livers perfused with oxygenated Krebs–Henseleit solution were exposed to reoxygenation following 20–minute hypoxia. The anoxic perfusion decreased bile output and reduced cyclic guanosine monophosphate (cGMP) contents, an index of nitric oxide (NO) generation. Upon reoxygenation, the decreased bile was not fully recovered, and the resistance increased biphasically: an early transient spike accompanied by an elevated release of ET–1 and a rise accompanied by a cGMP elevation in the later period. The initial vasoconstriction appeared to be mediated by both ET A and ET B receptors, as judged by inhibitory effects of their antagonists, BQ–485 and BQ-788, respectively, while the late elevation of the resistance was not attenuated by these reagents, but rather enhanced by the ET B blockade. The BQ–788 treatment attenuated the reoxygenation–induced cGMP elevation and induced bile acid-dependent choleresis. However, such a change upon the ET B blockade coincided with dissociation of a recovery of phospholipids and aggravation of cell injury. The BQ–788-elicited deterioration of reoxygenation–elicited changes was attenuated by NO supplement with S –nitroso– N –acetyl penicillamine. N ω –Nitro–l–arginine methyl ester, an NO synthase inhibitor, mimicked biliary changes elicited by the ET B blockade but without causing notable cell injury. Under these circumstances, coadministration of clotrimazole, an inhibitor of cytochrome P450 mono–oxygenases, elicited the injury comparable with that observed under the ET B blockade. These results suggest that ET B –mediated signaling limits excessive bile acid excretion and plays a protective role against reoxygenation injury through mechanisms involving both NO–dependent and –independent processes.
A novel hypothesis to explain the bronchconstrictor effect of deep inspiration in asthma
Authors: G P Burns
Journal: Thorax (2002)

Background: In healthy subjects deep inspiration transiently dilates the airways, while many asthmatic subjects show bronchoconstriction by a mechanism which is incompletely understood. We hypothesised that the negative intrathoracic pressure associated with deep inspiration occurring in the context of increased leakiness of the airway vasculature may temporarily increase airway oedema and thus reduce luminal diameter in subjects with asthma. Methods: The effects of non-forced deep inspiration and forced deep inspiration through resistance (generating enhanced negative intrathoracic pressure) on specific airway conductance (sGaw) were compared in 10 asthmatic and 11 healthy subjects. Each performed two respiratory manoeuvres: (1) sGaw was measured immediately after three deep inspirations without added resistance, each performed at a predetermined rate (equal to that when performed maximally through resistance); and (2) sGaw was measured immediately after three forced inspirations through resistance. Results: Compared with deep inspiration without added resistance, sGaw was significantly reduced after deep inspiration through resistance in the asthmatic group by a mean (SD) of –13.5 (11.0)% (p=0.003) but was unchanged in the control group (–0.5 (12.4)%, p=0.67). Conclusions: Given the similar time-volume relationship in the two manoeuvres, the reduction in sGaw is unlikely to be due to differences in smooth muscle behaviour. It is suggested that the enhanced negative intrathoracic pressure acting across the airway capillaries increases airway wall oedema and reduces airway calibre. Such a mechanism operational during normal rapid deep inspiration might contribute to bronchoconstriction after deep inspiration in subjects with asthma.
Substrate regulation of the nucleotide pool during regional ischaemia and reperfusion in an isolated rat heart preparation: a phosphorus-31 magnetic resonance spectroscopy analysis
Authors: S A. CAMACHO, W. W PARMLEY, T. L JAMES, H. ABE, S. T WU, E. H BOTVINICK, T. A WATTERS, N. SCHILLER, R. SIEVERS, J. WIKMAN-COFFELT
Journal: Cardiovascular Research (1988)

Isolated rat heart preparations were studied to characterise the alterations in high energy phosphates that occur during reversible regional ischaemia and to determine whether pyruvate, as the sole exogenous energy substrate, would attenuate the ischaemia induced depletion of the nucleotide pool when compared with glucose. Using phosphorus-31 magnetic resonance spectroscopy baseline concentrations of adenosine triphosphate, phosphocreatine, inorganic phosphate, and intracellular pH were compared with values during 30 min of left coronary artery occlusion followed by 30 min of reperfusion. These variables were related to changes in developed pressure, coronary flow, and oxygen consumption. In addition, the total nucleotide pool was evaluated by biochemical analysis of myocardial tissue extracts and coronary effluent. The ischaemic region was characterised by a dye staining technique and cross sectional echocardiographic measurements of regional myocardial wall thinning. In both glucose and pyruvate perfused groups, coronary flow and oxygen consumption decreased to 50-60% of control within 1 min of ischaemia and returned to baseline values with reflow. Developed pressure decreased to 50(9) and 74(8)% (mean(SEM] of control after 30 min of ischaemia in glucose and pyruvate perfused groups respectively. Reperfusion resulted in complete recovery of developed pressure in hearts perfused with pyruvate but not in the glucose group. Glucose perfused hearts had a greater decrease in intracellular pH during ischaemia (7.07(0.01) to 6.36(0.1] than pyruvate perfused hearts (7.06(0.02) to 6.83(0.04]. Reperfusion resulted in a rapid return to baseline intracellular pH in both groups. During ischaemia, adenosine triphosphate values decreased to a greater degree in glucose than in pyruvate perfused hearts (57(4) and 79(5)% of baseline respectively). Thirty minutes of reperfusion did not significantly improve adenosine triphosphate concentrations in either group. Phosphocreatine concentrations decreased to 52(7) and 75(6)% of baseline in glucose and pyruvate perfused groups respectively after the ischaemic period. Reperfusion resulted in normalisation of phosphocreatine values in the pyruvate but not in the glucose perfused group. Biochemical analysis of myocardial tissue extracts confirmed the spectroscopy data and showed that pyruvate inhibits the efflux of adenine nucleotide derivatives. Tissue concentrations of adenosine monophosphate were three times greater and adenosine 50% less after 30 min of ischaemia in the pyruvate perfused group.(ABSTRACT TRUNCATED AT 400 WORDS)
Clinical, histopathologic, and genetic features of pediatric primary myelofibrosis—An entity different from adults
Authors: Melissa R. DeLario, Andrea M. Sheehan, Ramona Ataya, Alison A. Bertuch, Carlos Vega, C. Renee Webb, Dolores Lopez‐Terrada, Lakshmi Venkateswaran
Journal: American Journal of Hematology (2012)

Primary myelofibrosis is a chronic myeloproliferative neoplasm characterized by cytopenias, leukoerythroblastosis, extramedullary hematopoiesis, hepatosplenomegaly and bone marrow fibrosis. Primary myelofibrosis is a rare disorder in adults; children are even less commonly affected by this entity, with the largest pediatric case series reporting on three patients. Most literature suggests spontaneous resolution of myelofibrosis without long term complications in the majority of affected children. We describe the clinical, pathologic, and molecular characteristics and outcomes of nineteen children with primary myelofibrosis treated in our center from 1984 to 2011. Most patients had cytopenia significant enough to require supportive therapy. No child developed malignant transformation and only five of the 19 children (26%) had spontaneous resolution of disease. Sequence analyses for JAK2V617F and MPLW515L mutations were performed on bone marrow samples from 17 and six patients, respectively, and the results were negative. In conclusion, analysis of this large series of pediatric patients with primary myelofibrosis demonstrates distinct clinical, hematologic, bone marrow, and molecular features from adult patients.
A Novel <i>CDC25B</i> Promoter–Based Oncolytic Adenovirus Inhibited Growth of Orthotopic Human Pancreatic Tumors in Different Preclinical Models
Authors: Helga L. Weber, Manuel Gidekel, Santiago Werbajh, Edgardo Salvatierra, Cecilia Rotondaro, Leonardo Sganga, Gabriela Acosta Haab, David T. Curiel, Eduardo G. Cafferata, Osvaldo L. Podhajcer
Journal: Clinical Cancer Research (2015)

We decided to construct a novel oncolytic adenovirus whose replication was driven by the CDC25B promoter for its use in preclinical models of pancreatic cancer.We placed the essential E1A gene under control of the CDC25B promoter. Based on preliminary data, we pseudotyped the adenovirus with a chimeric fiber of serotypes 5/3. We investigated the in vitro lytic effect and the in vivo therapeutic efficacy in combination with gemcitabine on human pancreatic tumor xenografts orthotopically growing in nude mice and in tumors growing in Syrian hamsters. We also assessed biochemical markers of hepatic toxicity and CA19.9 levels.AV25CDC exhibited a strong in vitro lytic effect on pancreatic cancer cells. In vivo administration of AV25CDC combined with gemcitabine in mice harboring subcutaneously growing SW1990 pancreatic tumors almost abrogated tumor growth. Nude mice harboring 15-day-old orthotopic tumors, treated intratumorally or systemically with AV25CDC combined with gemcitabine, exhibited 70% to 80% reduction in tumor size compared with control mice that lasted for at least 60 days. Chemovirotherapy treatment induced a return to normal levels of biochemical parameters of hepatic toxicity; these mice exhibited more than 90% reduction in CA19.9 serum levels compared with control. Chemovirotherapy efficacy was confirmed in mice harboring Mia PaCa-2 tumors and in Syrian hamster harboring HaP-T1 tumors. We observed that viral treatment disrupted tumor architecture and induced an increase in MMP-9 activity that might facilitate gemcitabine penetrability.These data demonstrate that AV25CDC is an effective oncolytic agent candidate for pancreatic cancer chemovirotherapy combination.
Separation of airway and tissue properties by transfer respiratory impedance and thoracic gas volume in reversible airway obstruction
Authors: F Marchal, N Bouaziz, C Baeyert, C Gallina, C Duvivier, R Peslin
Journal: European Respiratory Journal (1996)

The aim of this study was to establish the ability to estimate separate airway and tissue properties from transfer respiratory impedance (Zrs,tr) data in the presence of airway obstruction. Zrs,tr, thoracic gas volume (TGV) and airway resistance (Raw,pleth) were measured in the presence of obstruction and after use of a bronchodilator (BD) in 13 normal or asymptomatic asthmatic adults and 28 children with symptomatic asthma. An analytical approach was used to solve the equations of a simplified variant of DuBois' model, including airway resistance (Raw*) and inertance (Iaw), tissue compliance (Ct) and resistance (Rt) and pulmonary gas compliance (Cg). The equations of the model could not be reliably solved in four children before BD. Mean Raw,pleth was not different from mean Raw* in adults before (mean +/- SEM) (3.4 +/- 0.5 vs 3.1 +/- 0.3 hPa.s.L-1) or after BD (1.4 +/- 0.2 vs 1.8 +/- 0.2 hPa.s.L-1), or in children after BD (2.9 +/- 0.3 vs 3.2 +/- 0.2 hPa.s.L-1, respectively). In children before BD, Raw* was significantly underestimated compared with Raw,pleth (3.8 +/- 0.4 vs 5.4 +/- 0.6 hPa.s.L-1). Overall, a significant positive correlation was found between the difference [Raw,pleth - Raw*] and Raw,pleth (r = 0.82). In adults, BD induced a decrease in Raw* and Rt, an increase in Ct, and no change in Iaw. In children after BD, there was no significant change in Raw* or Ct, whilst Rt decreased and Iaw increased. Taking Raw,pleth as the gold standard, it is concluded that coherent estimation of parameters of DuBois' model may be obtained from combined Zrs,tr and TGV measurements in normal subjects and moderately obstructed adults, but not in children with significant airway obstruction. This seems to be due to the systematic under-estimation of Raw*.