tbuckley/cabot-search huggingface dataset:
Action of moguisteine on the activity of tracheobronchial rapidly adapting receptors in the dog
Authors: G Sant'Ambrogio, FB Sant'Ambrogio
Journal: European Respiratory Journal (1998)

We have studied the effects of moguisteine, a new non-narcotic, peripherally acting antitussive compound, on tracheobronchial rapidly adapting irritant receptors (RARs). Experiments were carried out on dogs anaesthetized with a mixture of urethane and alpha-chloralose, paralysed with gallamine, vagotomized and artificially ventilated. Single unit action potentials identified as originating from tracheobronchial RARs were recorded from the peripheral cut end of the right vagus nerve. The activity of these receptors was recorded together with oesophageal pressure and arterial blood pressure. Fourteen RARs were challenged with moguisteine (200 microg x kg[-1] i.v.) in 0.4% dimethylsulphoxide (DMSO) or 0.4% DMSO alone (vehicle). Receptor activity was recorded before (control) and at 2, 5, 10, 15, 20, 30 and 45 min after administration of the challenging compounds. When the results at intervals of 2, 5, 10, 15 and 20 min were averaged for each dog, it was found that moguisteine decreased the mean activity of the 14 receptors to 75% of the control value (p&lt;0.05); the greatest inhibition occurred 10-20 min after moguisteine administration. DMSO did not significantly affect the activity of these endings. Oesophageal pressure, arterial blood pressure and cardiac frequency were not altered during the experimental procedures. The overall results indicate the presence of an inhibitory effect of moguisteine on rapidly adapting irritant receptors that could account for the antitussigenic effect of this compound.
Outcomes in Patients With Diabetes Mellitus Undergoing Percutaneous Coronary Intervention in the Current Era
Authors: Verghese Mathew, Bernard J. Gersh, Brent A. Williams, Warren K. Laskey, James T. Willerson, R. Thomas Tilbury, Barry R. Davis, David R. Holmes
Journal: Circulation (2004)

Diabetes portends an adverse prognosis in patients undergoing percutaneous coronary intervention (PCI). Whether improvements in current clinical practice (stents, IIb/IIIa antagonists) have resulted in substantial improvement of these outcomes remains an issue. The aim of this study was to determine the influence of diabetes on 9-month outcomes of patients undergoing PCI in the current era.The 11 482 patients enrolled in the Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) Trial were stratified according to the presence (n=2694) or absence (n=8798) of diabetes. Diabetic patients were older; were more likely to be female; had a higher proportion of congestive failure, hypertension, prior CABG, and unstable angina; and had higher body mass index and lower ejection fraction than nondiabetic patients (P<0.01 for all comparisons). The degree of multivessel disease was similar between the two groups. American College of Cardiology/American Heart Association type C lesions were more common in diabetic patients (17% versus 15%, P<0.01). Angiographic and procedural success rates and in-hospital events were similar between the two groups. The primary end point of death, myocardial infarction, or target vessel revascularization (TVR) was analyzed as time-to-first event within 9 months of the index PCI. After adjusting for certain baseline characteristics, diabetes was independently associated with death at 9 months (relative risk [RR], 1.87; 95% CI, 1.31 to 2.68, P<0.01) and with an increased likelihood of TVR (RR, 1.27; 95% CI, 1.14 to 1.42, P<0.01), as well as the composite end point of death/myocardial infarction/TVR (RR, 1.26; 95% CI, 1.13 to 1.40, P<0.01).Despite advances in interventional techniques, diabetes remains a significant independent predictor of adverse events in the intermediate term after PCI.
Retinoids in cancer therapy.
Authors: M A Smith, D R Parkinson, B D Cheson, M A Friedman
Journal: Journal of Clinical Oncology (1992)

PURPOSE Recent reports of the dramatic antitumor effect of all-trans retinoic acid (RA) in patients with acute promyelocytic leukemia (APL) have generated renewed enthusiasm for clinical studies of retinoids for oncologic therapeutic indications. Here we provide an overview of relevant aspects of retinoid physiology and molecular biology, review preclinical studies indicating antitumor activity for retinoids, and summarize the current status of clinical investigations of retinoid use for the treatment of adult and pediatric tumors. DESIGN The published literature was reviewed with attention to areas of retinoid research that would shed insight into the oncologic uses of retinoids. RESULTS Retinoids play critical roles during normal fetal development and induce differentiation (and/or growth inhibition) in a variety of tumor-cell lines. Retinoid effects seem to result from changes in gene expression mediated via specific nuclear receptors (termed retinoic acid receptors, RAR-alpha, -beta, and -gamma), and a specific chromosomal translocation involving the RAR-alpha gene occurs in APL patients. In addition to the very high clinical response rate for RA in patients with APL, significant clinical responses have been observed for patients with cutaneous T-cell malignancies, juvenile chronic myelogenous leukemia, and dermatologic malignancies. Additionally, the combination of 13-cis-retinoic acid (cRA) with interferon alpha (IFN alpha) has produced high objective response rates for patients with squamous cell carcinomas of the head and neck and of the cervix. CONCLUSIONS The antitumor activity demonstrated for retinoids (especially RA) alone and in combination with other agents supports the need for targeted phase II trials to define the spectrum of responsive tumors and for laboratory studies to further delineate the biologic mechanisms associated with therapeutic responses. High priority should then be given to phase III trials to delineate optimal strategies for improving outcome by combining retinoid-based treatments with conventional chemotherapy and radiotherapy regimens.
Thrombin receptor expression in rheumatoid and osteoarthritic synovial tissue.
Authors: R Morris, P G Winyard, L F Brass, D R Blake, C J Morris
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To investigate the possibility that synovial cells might respond to thrombin in the inflamed human joint, using immunohistochemical detection of thrombin receptors. METHODS: Frozen sections of synovial membrane from 20 patients with rheumatoid arthritis, 16 with osteoarthritis, and four normal controls were stained using a monoclonal antibody to the human thrombin receptor. Sections were also double stained for both receptors and non-specific esterase. RESULTS: Receptor positive cells were present in rheumatoid synovia, with some cells also staining positively for non-specific esterase. In contrast, both osteoarthritic and normal synovia contained very few cells expressing receptors. CONCLUSIONS: Thrombin may mediate important pathological changes during chronic inflammatory joint disease.
DISSOCIATION OF MICROBIC SPECIES
Authors: Paul H. De Kruif
Journal: The Journal of Experimental Medicine (1921)

Two types of organism have been shown to exist in cultures of the bacillus of rabbit septicemia, recently isolated from spontaneous infections. One, Microbe D, grows diffusely in serum and plain broth, forms rather opaque, fluorescing colonies on serum agar, and is highly virulent for rabbits. These characters are retained throughout many passages in serum or plain broth. The other type, Microbe G, flocculates rapidly in fluid media, forms translucent) bluish colonies with little fluorescence, and exhibits extremely low virulence for rabbits. Like Microbe D, its distinguishing characters persist throughout many passages in artificial media. Two methods for the dissociation of these varieties from the parent culture have been described. The two types are morphologically indistinguishable and possess identical fermentation reactions. Rabbits surviving inoculation with Type G are resistant to multiple lethal doses of Type D. The agglutination reactions bear out this suggestion of the antigenic identity of the varieties. Community of antigenic character is rendered certain by the results of absorption reactions. Microbe D, in contact with immune serum, flocculates well at 55 degrees , but poorly or not at all at 37 degrees C. Microbe G, on the other hand, agglutinates easily at both temperatures. Microbe D, after being carried through twenty-five passages in serum and in plain broth, retains perfectly its characteristics of diffuse growth and of virulence, in the plain as well as in the serum broth.
Capillary C4d Deposition in Kidney Allografts
Authors: Georg A. Bo[Combining Diaeresis]hmig, Markus Exner, Antje Habicht, Martin Schillinger, Ursula Lang, Josef Kletzmayr, Marcus D. Sa[Combining Diaeresis]emann, Walter H. Ho[Combining Diaeresis]rl, Bruno Watschinger, Heinz Regele
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Capillary deposition of the complement split product C4d has been discussed as a marker for antibody-mediated kidney allograft rejection. The relationship between C4d staining and posttransplant alloantibody detection remains to be thoroughly investigated, however. In this study, C4d staining in peritubular capillaries (PTC) and the incidence of alloantibody formation, as detected with sensitive techniques, were evaluated among a cohort of transplant recipients who had undergone biopsies and had not been selected for a specific histologic diagnosis. One hundred thirteen biopsies, obtained from 58 cadaveric kidney transplant recipients, were tested. Serum samples obtained at the time of biopsy were evaluated by flow cytometric crossmatch (FCXM) testing and FlowPRA (One Lambda, Inc., Canoga Park, CA) analysis of anti-HLA panel reactivity. Most biopsies with C4d deposits in PTC (C4dPTC+, n = 21 of 24) were associated with positive posttransplant FCXM results (T and/or B cell FCXM) and/or ≥5% FlowPRA (anti-HLA class I and/or II) reactivity. Approximately 50% of the C4dPTC− biopsies were observed to be associated with donor-specific alloantibodies. Accordingly, high specificity (93%) but low sensitivity (31%) were calculated for capillary C4d staining (with FCXM testing as the standard method). For clinical evaluation, three patient groups were defined, i.e., a group of recipients with positive C4d staining in at least one allograft biopsy (C4dPTC+, n = 16) and two C4dPTC− groups, which were discriminated on the basis of posttransplant FCXM results as C4dPTC−/FCXM+ (n = 22) and C4dPTC−/FCXM− (n = 20) groups. Univariate analyses revealed significant differences between these groups with respect to serum creatinine levels at 12 mo [median, 2.83 mg/dl (interquartile range, 1.93 to 4.2 mg/dl) versus 1.78 mg/dl (1.47 to 2.24 mg/dl) versus 1.59 mg/dl (1.2 to 1.71 mg/dl), P < 0.001]. Of the five immunologic graft losses, four occurred in the C4dPTC+ group and one occurred in the C4dPTC−/FCXM+ group. In a multivariate analysis, C4d positivity was observed to have an independent predictive value for inferior 12-mo graft function (P = 0.02), whereas the observed moderate difference between C4dPTC−/FCXM+ and C4dPTC−/FCXM− recipients did not achieve significance. In conclusion, these data demonstrate that positive C4d staining, which is an independent predictor of kidney graft dysfunction, represents a reliable specific marker for antibody-dependent graft injury.
Fate of Left Ventricular Contraction following Aortocoronary Venous Grafts
Authors: MARTIAL G. BOURASSA, JACQUES LÉSPERANCE, LUCIEN CAMPEAU, JACQUES SALTIEL
Journal: Circulation (1972)

Changes in left ventriclar contraction were studied approximately two weeks and one year after surgery in 87 patients having 131 venous grafts. Nineteen out of 37 or 51% of the ventricular wall motion defects revascularized by patent and intact grafts were improved following surgery. Hypokinesis was improved in 17 out of 24 instances (70%) and a normal contraction was restored in nearly half of the cases. Akinesis was improved in two out of 13 instances (15%). Following inadequate venous grafts, 15 out of 35 or 42% of the normal wall segments and four out of 16 or 25% of the hypokinetic wall segments were worse after surgery and late akinesis was frequent. Aortocoronary bypass surgery is followed by significant improvement as well as deterioration of left ventricular contraction and function. The late result of surgery is determined by the fate of aortocoronary venous grafts.
Ultrasound Measurement of the Fibrous Cap in Symptomatic and Asymptomatic Atheromatous Carotid Plaques
Authors: Gérald Devuyst, Patrick Ruchat, Theodoros Karapanayiotides, Lisa Jonasson, Olivier Cuisinaire, Johannes-Alexander Lobrinus, Marc Pusztaszeri, Askenadios Kalangos, Paul-André Despland, Jean-Philippe Thiran, Julien Bogousslavsky
Journal: Circulation (2005)

Fibrous cap thickness (FCT) is an important determinant of atheroma stability. We evaluated the feasibility and potential clinical implications of measuring the FCT of internal carotid artery plaques with a new ultrasound system based on boundary detection by dynamic programming.We assessed agreement between ultrasound-obtained FCT values and those measured histologically in 20 patients (symptomatic [S]=9, asymptomatic [AS]=11) who underwent carotid endarterectomy for stenosing (>70%) carotid atheromas. We subsequently measured in vivo the FCT of 58 stenosing internal carotid artery plaques (S=22, AS=36) in 54 patients. The accuracy in discriminating symptomatic from asymptomatic plaques was assessed by receiver operating characteristic curves for the minimal, mean, and maximal FCT. Decision FCT thresholds that provided the best correct classification rates were identified. Agreement between ultrasound and histology was excellent, and interobserver variability was small. Ultrasound showed that symptomatic atheromas had thinner fibrous caps (S versus AS, median [95% CI]: minimal FCT=0.42 [0.34 to 0.48] versus 0.50 [0.44 to 0.53] mm, P=0.024; mean FCT=0.58 [0.52 to 0.63] versus 0.79 [0.69 to 0.85] mm, P<0.0001; maximal FCT=0.73 [0.66 to 0.92] versus 1.04 [0.94 to 1.20] mm, P<0.0001). Mean FCT measurement demonstrated the best discriminatory accuracy (area under the curve [95% CI]: minimal 0.74 [0.61 to 0.87]; mean 0.88 [0.79 to 0.97]; maximal 0.82 [0.71 to 0.93]). The decision threshold of 0.65 mm (mean FTC) demonstrated the best correct classification rate (82.8%; positive predictive value 75%, negative predictive value 88.2%).FCT measurement of carotid atheroma with ultrasound is feasible. Discrimination of symptomatic from asymptomatic plaques with mean FCT values is good. Prospective studies should determine whether this ultrasound marker is reliable.
Impaired Sensory Processing as a Basis for Object-Recognition Deficits in Schizophrenia
Authors: G M Doniger, G Silipo, E F Rabinowicz, J G Snodgrass, D C Javitt
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Individuals are able to recognize common objects even when portions of them are obscured from view, reflecting the operation of neural perceptual closure processes. This study evaluates the integrity of object recognition and perceptual closure as a function of sensory and cognitive manipulations. METHOD: Object recognition was examined in 26 subjects with schizophrenia and 23 nonpsychiatric comparison subjects of similar age with a presentation of fragmented pictures by means of the ascending method of limits. The effects of prior exposure to subsets of stimuli and of word prompting were examined in separate testing phases. Demographic and clinical characteristics were evaluated as covariates. RESULTS: Although they had impairments in perceptual closure, schizophrenic patients showed improvement in performance equivalent to that of nonpatient comparison subjects with prior exposure to the pictures (i.e., repetition priming) and with presentation of valid word prompts. A significant correlation was found between impaired performance and the severity of negative symptoms. CONCLUSIONS: The results support models of widespread dysfunction in information processing in patients with schizophrenia involving both sensory and cognitive regions. Perceptual closure is significantly impaired in schizophrenic patients; however, this deficit in sensory precision is dissociated from the effects of higher-order repetition priming and word prompting. Furthermore, this work suggests that deficits in perceptual closure may contribute to the muted world experience of patients with the persistent negative symptoms of schizophrenia.
<i>In vivo</i> Imaging of Tumor Transduced with Bimodal Lentiviral Vector Encoding Human Ferritin and Green Fluorescent Protein on a 1.5T Clinical Magnetic Resonance Scanner
Authors: Hoe Suk Kim, Hye Rim Cho, Seung Hong Choi, Ji Su Woo, Woo Kyung Moon
Journal: Cancer Research (2010)

A combination of reporter genes for magnetic resonance imaging (MRI) and optical imaging can provide an additional level of noninvasive and quantitative information about biological processes occurring in deep tissues. We developed a bimodal lentiviral vector to monitor deep tissue events using MRI to detect myc-tagged human ferritin heavy chain (myc-hFTH) expression and fluorescence imaging to detect green fluorescent protein (GFP) expression. The transgene construct was stably transfected into MCF-7 and F-98 cells. After transplantation of the cells expressing myc-hFTH and GFP into mice or rats, serial MRI and fluorescence imaging were performed with a human wrist coil on a 1.5T MR scanner and optical imaging analyzer for 4 weeks. No cellular toxicity due to overexpression of myc-hFTH and GFP was observed in MTT and trypan blue exclusion assays. Iron accumulation was observed in myc-hFTH cells and tumors by Prussian blue staining and iron binding assays. The myc-hFTH cells and tumors had significantly lower signal intensities in T(2)-weighted MRI than mock-transfected controls (P ≤ 0.05). This is direct evidence that myc-hFTH expression can be visualized noninvasively with a 1.5T clinical MR scanner. This study shows that MRI and fluorescence imaging of transplanted cells at molecular and cellular levels can be performed simultaneously using our bimodal lentiviral vector system. Our techniques can be used to monitor tumor growth, metastasis, and regression during cell and gene-based therapy in deep tissues.
Secular Trends in Nosocomial Infections and Mortality Associated With Noninvasive Ventilation in Patients With Exacerbation of COPD and Pulmonary Edema
Authors: Emmanuelle Girou, Christian Brun-Buisson, Solenne Taillé, François Lemaire, Laurent Brochard
Journal: JAMA (2003)

Randomized controlled trials have shown that the use of noninvasive ventilation (NIV) reduces the need for endotracheal intubation and invasive mechanical ventilation and reduces complication rates and mortality in selected groups of patients. But whether these benefits translate to a clinical setting is unclear.To evaluate longitudinally the routine implementation of NIV and its effect on patients admitted to the intensive care unit (ICU) with acute exacerbation of chronic obstructive pulmonary disease (COPD) or severe cardiogenic pulmonary edema (CPE).Retrospective, observational cohort study using prospectively collected data from January 1, 1994, through December 31, 2001.A 26-bed medical intensive care unit (ICU) of a French university referral hospital.A cohort of 479 consecutive patients ventilated for acute exacerbation of COPD or CPE.The ICU mortality and incidence rates of ICU-acquired infections.A significant increase in NIV use and a concomitant decrease in mortality and ICU-acquired infection rates were observed over the study years. With adjustment for relevant covariates and propensity scores, NIV was identified as an independent factor linked with a reduced risk of death in the cohort (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.18-0.78), whereas a high severity score on admission (OR, 1.05; 95% CI, 1.01-1.10) and the occurrence of a nosocomial infection (OR, 3.08; 95% CI, 1.62-5.84) were independently associated with death. Rates of ICU-acquired pneumonia decreased from 20% in 1994 to 8% in 2001 (P =.04).Implementing routine use of NIV in critically ill patients with acute exacerbation of COPD or severe CPE was associated with improved survival and reduction of nosocomial infections.
Assisted reproduction treatment and epigenetic inheritance
Authors: A.P.A. van Montfoort, L.L.P. Hanssen, P. de Sutter, S. Viville, J.P.M. Geraedts, P. de Boer
Journal: Human Reproduction Update (2012)

The subject of epigenetic risk of assisted reproduction treatment (ART), initiated by reports on an increase of children with the Beckwith–Wiedemann imprinting disorder, is very topical. Hence, there is a growing literature, including mouse studies. In order to gain information on transgenerational epigenetic inheritance and epigenetic effects induced by ART, literature databases were searched for papers on this topic using relevant keywords. At the level of genomic imprinting involving CpG methylation, ART-induced epigenetic defects are convincingly observed in mice, especially for placenta, and seem more frequent than in humans. Data generally provide a warning as to the use of ovulation induction and in vitro culture. In human sperm from compromised spermatogenesis, sequence-specific DNA hypomethylation is observed repeatedly. Transmittance of sperm and oocyte DNA methylation defects is possible but, as deduced from the limited data available, largely prevented by selection of gametes for ART and/or non-viability of the resulting embryos. Some evidence indicates that subfertility itself is a risk factor for imprinting diseases. As in mouse, physiological effects from ART are observed in humans. In the human, indications for a broader target for changes in CpG methylation than imprinted DNA sequences alone have been found. In the mouse, a broader range of CpG sequences has not yet been studied. Also, a multigeneration study of systematic ART on epigenetic parameters is lacking. The field of epigenetic inheritance within the lifespan of an individual and between generations (via mitosis and meiosis, respectively) is growing, driven by the expansion of chromatin research. ART can induce epigenetic variation that might be transmitted to the next generation.
US doctors and patients are split on approval of generic thyroid hormone
Authors: Janice Hopkins Tanne
Journal: BMJ (2004)

Three groups representing 4600 US endocrinologists have said in a public statement that they are “deeply disappointed” that the Food and Drug Administration has approved generic substitutes for brandname levothyroxine. Patient groups have welcomed the news, however, with one group announcing on its website: “The Generics are Coming, The Generics are Coming!!!” (www.thyroid.about.com/od/thyroiddrugtreatments/a/generic.htm).

Levothyroxine is the second most commonly prescribed drug in the United States, with sales worth $1.19bn (£0.64bn; €0.96bn) in 2003. Abbott Laboratories' market leader, Synthroid, had sales of nearly $820m, says IMS Health, a major pharmaceutical information and consulting company. More than 13 million people take the drug.

The American Thyroid Association, the Endocrine Society, and the American Society of Clinical Endocrinologists said: “Small differences between doses—well within the range of formulation differences that might …
Plasma kininogen and kininogen fragments are biomarkers of progressive renal decline in type 1 diabetes
Authors: Michael L. Merchant, Monika A. Niewczas, Linda H. Ficociello, Janice A. Lukenbill, Daniel W. Wilkey, Ming Li, Syed J. Khundmiri, James H. Warram, Andrzej S. Krolewski, Jon B. Klein
Journal: Kidney International (2013)