tbuckley/cabot-search huggingface dataset:
STUDIES ON BACILLUS MURISEPTICUS, OR THE ROTLAUF BACILLUS, ISOLATED FROM SWINE IN THE UNITED STATES
Authors: Carl Tenbroeck
Journal: The Journal of Experimental Medicine (1920)

In the United States organisms, which culturally are mouse septicemia or swine erysipelas bacilli, have been isolated from the tonsils of five of sixteen pigs examined. These pigs all had hog-cholera, but it is probable that the bacilli were in the tonsils before they were infected with hog-cholera, and there is no evidence that they played any part in the disease. The distribution of the infection seemed to be restricted as most of the pigs from which the bacilli were obtained came from one litter. As we do not have clinical rotlauf, or swine erysipelas, in this country, as these organisms, in Europe, have been found in a large percentage of apparently normal swine, and as the disease is produced with difficulty by the injection of cultures, the question may be raised whether they are not secondary invaders rather than the primary cause of the disease with which they have been associated, or else whether the resistance of swine on the European continent does not differ from that of our breeds as a result of differences in foods. It is possible that the mouse septicemia bacilli found in this country may differ culturally from those present in animals with swine erysipelas. With this in mind, the carbohydrate reactions, as well as other cultural characters not necessary for the identification of the bacilli isolated, have been studied. The disease produced by the injection of these bacilli into mice and pigeons has been studied and shown to be largely an intracellular process. The organisms are taken up by the endothelial cells lining the veins and capillaries; there they multiply and soon kill the cells. It has also been shown that the only type of cell in the blood stream which contains bacteria is the endothelial leucocyte, and the probabilities are that the free phagocytes have been detached from the lining of the vessels. The disease is acute, and the indications are that in the cells the bacilli find a favorable medium for their growth. While phagocytosis may in general be an immune reaction, in this case it appears to favor the parasite rather than the host.
Angiotensin-Converting Enzyme Inhibition and AT1 Receptor Blockade Modify the Pressure-Natriuresis Relationship by Additive Mechanisms in Rats with Human Renin and Angiotensinogen Genes
Authors: EERO MERVAALA, BASTIAN DEHMEL, VOLKMAR GROSS, ANDREA LIPPOLDT, JÜRGEN BOHLENDER, ANNA FRANCA MILIA, DETLEV GANTEN, FRIEDRICH C. LUFT
Journal: Journal of the American Society of Nephrology (1999)

Abstract. The intrarenal factors responsible for hypertension in double-transgenic rats (dTGR) harboring human renin and human angiotensinogen genes are unclear. The pressure-natriuresis and -diuresis relationships in response to chronic angiotensin-converting enzyme (ACE) inhibition and AT 1 receptor blockade were evaluated. Renal renin-angiotensin and nitric oxide (NO) system gene expression was also investigated. Six-week-old dTGR were treated for 3 wk with submaximal doses of cilazapril (10 mg/kg, orally) or losartan (10 mg/kg, orally) or with the drug combination. In untreated dTGR, pressure-natriuresis relationships were maximally shifted rightward by approximately 70 to 80 mmHg, and both renal blood flow (RBF) and GFR were markedly decreased. Submaximal cilazapril and losartan dosages both decreased systolic BP by 30 mmHg and shifted the pressure-natriuresis curves leftward by 25 to 30 mmHg. Cilazapril increased RBF and GFR to values observed in normotensive control animals but did not significantly affect fractional sodium excretion (FENa) or fractional water excretion (FEH 2 O) curves. In contrast, losartan had no significant effect on RBF or GFR but shifted the FENa and FEH 2 O curves leftward. The cilazapril and losartan combination completely normalized BP and shifted the pressure-natriuresis curves leftward more than did either drug alone. When cilazapril and losartan were administered at higher doses (30 mg/kg, orally), the two drugs equally shifted the pressure-natriuresis curves leftward, by 50 mmHg. Both drugs increased RBF and GFR; however, only losartan shifted FENa and FEH 2 O curves leftward. Human and rat renin and angiotensinogen genes were downregulated in dTGR and were increased by losartan and cilazapril treatments, whereas no changes in the expression of rat ACE and AT 1A receptor genes were observed. Endothelial NO synthase expression was increased by cilazapril but not by losartan. Neither inducible NO synthase nor neural NO synthase gene expression was affected by drug treatments. Therefore, submaximal ACE inhibition enhanced sodium excretion mainly by increasing RBF and GFR, whereas submaximal AT 1 receptor blockade decreased tubular sodium and water reabsorption. The combination of the two drugs produced an additive effect. The ACE inhibitor effects may involve increased endothelial NO synthase expression, perhaps related to the inhibition of bradykinin degradation.
The Molecular Basis of Colon Cancer
Authors: Anil K. Rustgi, Daniel K. Podolsky
Journal: Annual Review of Medicine (1992)

There are approximately 160,000 new cases of colon cancer every year in the United States. Colon carcinoma results from the aggregate effects of multiple genetic alterations. Some genetic alterations may be inherited, while others reflect somatic mutations. The latter may themselves be the indirect result of environmental factors such as diet. It is the total accumulation of these genetic changes, combining the activation of oncogenes with the inactivation of tumor suppressor genes, that is responsible for determining the biologic properties of colon cancer.
Abstract 15020: Ablation of Paroxysmal Atrial Fibrillation Applying an Improved Cryoballoon: is Reduction of Freezing Time Possible?
Authors: Georg Nölker, Stephan Molatta, Frauke Koch, M. Sajid Hossain, Kevin Bullert, Dieter Horstkotte, Klaus-Jürgen Gutleben
Journal: Circulation (2014)

Introduction: Cryoballoon (CB) ablation has been adopted by many centers worldwide for treatment of atrial fibrillation (AF). An improved version of the CB providing homogeneous cooling at its total frontal side has been introduced (Arctic Front Advance™, Medtronic). Hypothesis: We aimed to evaluate whether reduction of cooling times in application of this advanced CB is possible without affecting the outcome. Methods: A total of 94 patients (pts) (44 male, 58 ± 13 years) suffering from paroxysmal AF were prospectively assigned to CB pulmonary vein isolation choosing either 2 x 4 minutes (group 1) or 2 x 3 minutes (group 2) of freezing per vein. In case of pull-down maneuvers 120 s application time at the superior edge was followed by additional freezing of 3 or 4 minutes respectively after pull-down. Follow-up at 3, 6 months completed in all pts. included a clinical visit and a 7-day Holter or a readout of an implanted device for evaluation of AF burden. Results: Groups were well balanced in terms of left atrial size, left ventricular function, concomitant diseases and duration of AF. Total procedure time was reduced from 116±28 to 109±23 minutes (p=n.s.). Freezing time per pt decreased from 38.7±8.2 to 31.2±6.9 minutes (p&lt;0.00001). Fluoroscopy time was similar between the groups (10.3±5.8; 12.1±5.5 min.; p=n.s.). During a follow-up of 6.4±1.8 months recurrence of AF was observed in 11 % of pts in group 1 versus 29 % of pts in group 2 (p=0.04). No major complications occurred in either group. Conclusions: Based on our preliminary findings, reduction of freezing time in CB ablation applying the improved version of the CB catheter seems to increase recurrence of AF. Therefore, it might be advisable to maintain longer freezing times. A prolonged follow-up will be available and presented at the meeting.
Latest developments in the treatment of melanoma: ‘a penicillin moment for cancer’?
Authors: Spyros Retsas
Journal: Journal of the Royal Society of Medicine (2011)

Two papers, each with an accompanying editorial, published recently in the New England Journal of Medicine, shattered the stagnant waters of melanoma therapeutics.1–4

The first1,2 made a bold claim that survival of patients with metastatic melanoma could be improved with treatment with Ipilimumab, a monoclonal antibody that potentiates anti-tumour immunity, despite only a small number of treated patients experiencing a significant resolution of their tumours.

The second paper3,4 claimed instead an audacious 81% response rate resulting in major regression of large tumour volumes achieved with a new drug, Plexxikon (PLX4032 or RG7204), that targets the V600E B-RAF mutation harboured by some patients with metastatic melanoma. Despite such major responses an impact on survival remains at this point uncertain.

These observations for a cancer perceived by many to be refractory to all treatment merit a critical appraisal.
High-density lipoprotein stimulates endothelial cell movement by a mechanism distinct from basic fibroblast growth factor.
Authors: G Murugesan, G Sa, P L Fox
Journal: Circulation Research (1994)

Endothelial cell (EC) migration is a regulatory event in the formation and repair of blood vessels. Although serum contains substantial promigratory activity, the responsible components and especially the role of lipoproteins have not been determined. We examined the effect of plasma high-density lipoprotein (HDL) on the movement of ECs in vitro. Confluent cultures of bovine aortic ECs in serum-free medium were "wounded," and migration was measured after 24 hours. HDL stimulated migration in a concentration-dependent manner with a half-maximal response at 25 to 40 micrograms cholesterol per milliliter and a maximal twofold stimulation at approximately 150 micrograms cholesterol per milliliter. HDL-stimulated migration was not due to cell proliferation, since migration was increased in the presence of hydroxyurea at a concentration that blocked proliferation. At optimal concentrations, HDL was at least as stimulatory as basic fibroblast growth factor (FGF). However, the activity of HDL was not due to contamination by basic FGF, since antibodies to basic FGF did not block HDL-stimulated movement and since the maximum promigratory activities of basic FGF and HDL were additive. These results indicate that HDL and basic FGF may use distinct signaling pathways to initiate EC movement. This possibility was confirmed by results showing that pertussis toxin suppressed basic FGF-stimulated but not HDL-stimulated EC motility and that inhibitors of phospholipase A2, aristolochic acid and ONO-RS-082, also blocked the promigratory activity of basic FGF but had no effect on the activity of HDL.(ABSTRACT TRUNCATED AT 250 WORDS)
Allergic rhinitis and asthma require an integrated management
Authors: Paulo Camargos, Cássio Ibiapina, Laura Lasmar, Álvaro A Cruz
Journal: Thorax (2012)

We read with interest and congratulate the authors de Groot et al for the article on the impact of comorbid allergic rhinitis (AR) on asthma control in children.1 We entirely agree with de Groot and coworkers that despite its high prevalence, surprisingly there are few studies on the effects of treatment of AR in asthmatic children and adolescents.

Considering its high frequency and association with poor control of asthma, among untreated and even treated subjects,2 it is noteworthy that in low–middle income …
Antibodies Neutralizing Hepsin Protease Activity Do Not Impact Cell Growth but Inhibit Invasion of Prostate and Ovarian Tumor Cells in Culture
Authors: Jian-Ai Xuan, Doug Schneider, Pam Toy, Rick Lin, Alicia Newton, Ying Zhu, Silke Finster, David Vogel, Bob Mintzer, Harald Dinter, David Light, Renate Parry, Mark Polokoff, Marc Whitlow, Qingyu Wu, Gordon Parry
Journal: Cancer Research (2006)

Hepsin is a type II transmembrane serine protease that is expressed in normal liver, and at lower levels in kidney, pancreas, and testis. Several studies have shown that hepsin mRNA is significantly elevated in most prostate tumors, as well as a significant fraction of ovarian and renal cell carcinomas and hepatomas. Although the overexpression of mRNA in these tumors has been extensively documented, there has been conflicting literature on whether hepsin plays a role in tumor cell growth and progression. Early literature implied a role for hepsin in human tumor cell proliferation, whereas recent studies with a transgenic mouse model for prostate cancer support a role for hepsin in tumor progression and metastases. To evaluate this issue further, we have expressed an activatable form of hepsin, and have generated a set of monoclonal antibodies that neutralize enzyme activity. The neutralizing antibodies inhibit hepsin enzymatic activity in biochemical and cell-based assays. Selected neutralizing and nonneutralizing antibodies were used in cell-based assays with tumor cells to evaluate the effect of antibodies on tumor cell growth and invasion. Neutralizing antibodies failed to inhibit the growth of prostate, ovarian, and hepatoma cell lines in culture. However, potent inhibitory effects of the antibodies were seen on invasion of ovarian and prostate cells in transwell-based invasion assays. These results support a role for hepsin in tumor cell progression but not in primary tumor growth. Consistent with this, immunohistochemical experiments with a mouse monoclonal antibody reveal progressively increased staining of prostate tumors with advanced disease, and in particular, extensive staining of bone metastatic lesions.
Integration of DNA Copy Number Alterations and Prognostic Gene Expression Signatures in Breast Cancer Patients
Authors: Hugo M. Horlings, Carmen Lai, Dimitry S.A. Nuyten, Hans Halfwerk, Petra Kristel, Erik van Beers, Simon A. Joosse, Christiaan Klijn, Petra M. Nederlof, Marcel J.T. Reinders, Lodewyk F.A. Wessels, Marc J. van de Vijver
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Several prognostic gene expression profiles have been identified in breast cancer. In spite of this progress in prognostic classification, the underlying mechanisms that drive these gene expression patterns remain unknown. Specific genomic alterations, such as copy number alterations, are an important factor in tumor development and progression and are also associated with changes in gene expression. Experimental Design: We carried out array comparative genomic hybridization in 68 human breast carcinomas for which gene expression and clinical data were available. We used a two-class supervised algorithm, Supervised Identification of Regions of Aberration in aCGH data sets, for the identification of regions of chromosomal alterations that are associated with specific sample labeling. Using gene expression data from the same tumors, we identified genes in the altered regions for which the expression level is significantly correlated with the copy number and validated our results in public available data sets. Results: Specific chromosomal aberrations are related to clinicopathologic characteristics and prognostic gene expression signatures. The previously identified poor prognosis, 70-gene expression signature is associated with the gain of 3q26.33-27.1, 8q22.1-24.21, and 17q24.3-25.1; the 70-gene good prognosis profile is associated with the loss at 16q12.1-13 and 16q22.1-24.1; basal-like tumors are associated with the gain of 6p12.3-23, 8q24.21-22, and 10p12.33-14 and losses at 4p15.31, 5q12.3-13.1, 5q33.1, 10q23.33, 12q13.13-3, 15q15.1, and 15q21.1; HER2+ breast show amplification at 17q11.1-12 and 17q21.31-23.2 (including HER2 gene). Conclusions: There is a strong correlation between the different gene expression signatures and underlying genomic changes. These findings help to establish a link between genomic changes and gene expression signatures, enabling a better understanding of the tumor biology that causes poor prognosis. Clin Cancer Res; 16(2); 651–63
End points for pulmonary arterial hypertension: a way backward
Authors: M. Sofia, M. Maniscalco, P. Carratù, O. Resta
Journal: European Respiratory Journal (2004)

restriction does not apply to the occasional marijuana smoker.In conclusion, lung donation after fatal acute poisoning, although difficult, could be considered in selected cases of poisoning by pharmaceutical drugs that are not associated with lung injury and in selected cases of pure carbon monoxide intoxication.Oral ecstasy poisoning, as well as occasional marijuana smoking, do not appear to be an absolute contraindication.
Localization of foetal antigen 2 (FA-2) in foetal and adult human skin
Authors: H. BOJE RASMUSSEN, B. TEISNER, J. CHEMNITZ, J. MOLLER RASMUSSEN, F. BRANDRUP
Journal: British Journal of Dermatology (1989)

Foetal antigen 2 (FA-2) is a connective-tissue-associated antigen isolated from second trimester human amniotic fluid. FA-2 has an α-electrophoretic mobility and is a single-chain molecule with a molecular weight of 26 kDa as determined by polyacrylamide gel electrophoresis (PAGE). Using indirect immunofluorescence and the immunoperoxidase technique, FA-2 was found to be in the lamina densa/ sublamina densa region of the basement membrane zone (BMZ) in adult as well as in foetal skin. FA-2 was found throughout the dermis in foetal skin, whereas in adult skin it was found to be associated with the BMZ and around the blood vessels, hair follicles and eccrine glands. Intracellular FA-2 antigen was demonstrated in proliferating fibroblasts by the indirect immunoperoxidase technique and immunoelectron microscopy of the fibroblasts revealed staining of the antigen in the cisternae of the rough endoplasmatic reticulum at the trans-side of the Golgi complex as well as in vesicles close to the plasma membranes. FA-2, a hitherto undescribed antigen associated with human BMZ, is probably being synthesized by proliferating fibroblasts.
The position of the acid pocket as a major risk factor for acidic reflux in healthy subjects and patients with GORD
Authors: H. Beaumont, R. J Bennink, J. de Jong, G. E Boeckxstaens
Journal: Gut (2009)

<h3>Introduction</h3> Gastro-oesophageal reflux occurs twice as much during transient lower oesophageal sphincter relaxations (TLOSRs) in patients with gastro-oesophageal reflux disease (GORD) compared to healthy volunteers (HVs). Our aim was to assess whether the localisation of the postprandial acid pocket and its interaction with a hiatal hernia (HH) play a role in the occurrence of acidic reflux during TLOSRs. <h3>Methods</h3> Ten HVs and 22 patients with GORD (12 with HH&lt;3 cm (s-HH), 10 with HH≥3 cm (l-HH)) were studied. The squamocolumnar junction and diaphragmatic impression were marked with a radioactively labelled clip. To visualise the acid pocket, <sup>99m</sup>Tc-pertechnetate was injected intravenously and images were acquired up to 2 h postprandial. Concurrently, combined manometry/impedance and four-channel pH-metry were performed, with pH pull-through at multiple time-points. <h3>Results</h3> The rate of TLOSRs and the per cent associated with reflux was comparable between all groups. However, acidic reflux was significantly increased in patients, especially in patients with l-HH. Acid pocket length was significantly enlarged in patients. Moreover, immediately before a TLOSR, the acid pocket was more frequently located within the hiatus or above the diaphragm in patients with GORD (s-HH, 54%; l-HH, 77%) compared to HVs (22% of TLOSRs). Acidic reflux was significantly increased when the acid pocket was located above the diaphragm in all groups compared to a sub-diaphragmatic localisation. <h3>Conclusion</h3> The position of the acid pocket is largely determined by the presence of a HH. Entrapment of the pocket above the diaphragm, especially in patients with l-HH, is a major risk factor underlying the increased occurrence of acidic reflux during a TLOSR in patients with GORD.
Recent Advances in the Management of AIDS-related Opportunistic Infections
Authors: H. Clifford Lane
Journal: Annals of Internal Medicine (1994)

Secondary infections remain the leading cause of death in patients with the acquired immunodeficiency syndrome (AIDS). Dealing with the rapidly evolving spectrum of infectious problems seen in patients with AIDS requires knowledge of current therapeutic and prophylactic strategies. Through an extensive preclinical trials network supported by both industry and government, an increasing number of new agents are being identified and rapidly moved into clinical trials. Several agents are now available to treat diseases caused by Pneumocystis carinii, and corticosteroids have become a useful adjunct to antimicrobial agents in the treatment of P. carinii pneumonia. Although the treatment of toxoplasmosis remains a challenge, alternatives to sulfadiazine and pyrimethamine are now available. Mycobacterial infections, particularly with Mycobacterium tuberculosis, have become an increasing problem for patients with AIDS, and both old and new combination drug regimens are being used. Cytomegalovirus disease, until recently an untreatable problem, can now at least be partially managed with antiviral agents. The use of more complete prophylactic regimens may decrease the morbidity and mortality from opportunistic infections.
Chlamydia pneumoniae seroprevalence in immunocompetent and immunocompromised populations in Milan.
Authors: F Blasi, R Cosentini, M C Schoeller, A Lupo, L Allegra
Journal: Thorax (1993)

BACKGROUND--Chlamydia pneumoniae is drawing increasing attention as an agent of respiratory tract infection. Specific antibody prevalence in western countries is low in preschool children and reaches more than 50% in adults. However, little is known about the prevalence of this infection in immunocompromised subjects such as HIV-I infected patients. The aim of this study was to evaluate the seroprevalence of Chl pneumoniae in immunocompetent and immunocompromised (HIV-1 infected) paediatric and adult populations. METHODS--Between March 1991 and September 1992 764 healthy subjects (421 men and 343 women, age range six months-81 years), 96 HIV-I infected (73 men and 23 women, age range 18-35 years) and 126 HIV-I negative intravenous drug users (92 men and 34 women, age range 18-37 years), and 50 children (23 boys and 27 girls, age range 8-123 months) with vertically transmitted HIV-I infection were studied. For each subject an HIV-I test (ELISA and Western blot) was performed, together with a microimmunofluorescence test for IgG and IgM antibodies to Chl pneumoniae specific antigen (TW-183). RESULTS--In the healthy population a low prevalence (11%) was observed in children under 10 years of age, which increased progressively to 58% in adults over 70 years. In the HIV-I infected population Chl pneumoniae seroprevalence was higher than in immunocompetent controls (children, 26% v 11%; drug users, 60% v 40%). Moreover, in drug users this difference was also observed in comparison with HIV-1 negative intravenous drug users (60% v 33%). CONCLUSIONS--Our data on Chl pneumoniae seroprevalence in a healthy population are consistent with those reported by others in western countries. Moreover, HIV-I infected subjects seem to be at higher risk of developing Chl pneumoniae infections.