tbuckley/cabot-search huggingface dataset:
Which apparatus for inhaled pentamidine? A comparison of pulmonary deposition via eight nebulisers
Authors: SH Thomas, MJ O'Doherty, CJ Page, TO Nunan, NT Bateman
Journal: European Respiratory Journal (1991)

Aerosolised pentamidine 300 mg in 5 or 6 ml solution was administered via 8 different nebuliser systems to 12 patients with acquired immunodeficiency syndrome. Using 99mTc human serum albumin as an indirect marker for pentamidine, pulmonary, extrapulmonary (gastric and oropharyngeal) and alveolar deposition of pentamidine were measured using a gamma camera. Side effects (visual analogue scales) and changes in lung function associated with each treatment were also quantified. Deposition was completed more rapidly with the ultrasonic than the jet nebulisers. Mean total pulmonary depositions (mg +/- SEM) were Respirgard II, 6.1 +/- 0.5; Centimist, 7.3 +/- 1.0, System 22 Mizer, 14.3 +/- 2.1; System 22 Mizer with particle separator; 4.5 +/- 0.4; System 22 Mizer with Optimist 2, 6.3 +/- 0.9; Fisoneb, 6.0 +/- 1.2; Pentasonic (Portasonic); 4.6 +/- 0.9; Samsonic, 2.9 +/- 0.4. Differences between the nebulisers for peripheral lung and alveolar deposition reflected this pattern. Side effects scores were largest with System 22 Mizer, Pentasonic (Portasonic), and Fisoneb, and these produced the greatest oropharyngeal and gastric deposition. The largest reductions in lung function were associated with System 22 Mizer. A 300 mg dose of pentamidine nebulised via Respirgard II is known to be effective prophylaxis for Pneumocystis carinii pneumonia when given once monthly. Our results show that equivalent pulmonary deposition can be produced by other nebulisers. System 22 Mizer gives over twice the deposition associated with Respirgard II, and used with a pentamidine dose of 150 mg is likely to produce an adequate lung dose for prophylaxis. This nebuliser, however, is associated with more marked side effects.
A National Study of Outcomes among HIV-Infected Kidney Transplant Recipients
Authors: Jayme E. Locke, Shikha Mehta, Rhiannon D. Reed, Paul MacLennan, Allan Massie, Anoma Nellore, Christine Durand, Dorry L. Segev
Journal: Journal of the American Society of Nephrology (2015)

Kidney transplantation is a viable treatment for select patients with HIV and ESRD, but data are lacking regarding long-term outcomes and comparisons with appropriately matched HIV-negative patients. We analyzed data from the Scientific Registry of Transplant Recipients (SRTR; 2002-2011): 510 adult kidney transplant recipients with HIV (median follow-up, 3.8 years) matched 1:10 to HIV-negative controls. Compared with HIV-negative controls, HIV-infected recipients had significantly lower 5-year (75.3% versus 69.2%) and 10-year (54.4% versus 49.8%) post-transplant graft survival (GS) (hazard ratio [HR], 1.37; 95% confidence interval [95% CI], 1.15 to 1.64; P<0.001) that persisted when censoring for death (HR, 1.43; 95% CI, 1.12 to 1.84; P=0.005). However, compared with HIV-negative/hepatitis C virus (HCV)-negative controls, HIV monoinfected recipients had similar 5-year and 10-year GS, whereas HIV/HCV coinfected recipients had worse GS (5-year: 64.0% versus 52.0%, P=0.02; 10-year: 36.2% versus 27.0%, P=0.004 [HR, 1.38; 95% CI, 1.08 to 1.77; P=0.01]). Patient survival (PS) among HIV-infected recipients was 83.5% at 5 years and 51.6% at 10 years and was significantly lower than PS among HIV-negative controls (HR, 1.34; 95% CI, 1.08 to 1.68; P<0.01). However, PS was similar for HIV monoinfected recipients and HIV-negative/HCV-negative controls at both times. HIV/HCV coinfected recipients had worse PS compared with HIV-negative/HCV-infected controls (5-year: 67.0% versus 78.6%, P=0.007; 10-year: 29.3% versus 56.23%, P=0.002 [HR, 1.57; 95% CI, 1.11 to 2.22; P=0.01]). In conclusion, HIV-negative and HIV monoinfected kidney transplant recipients had similar GS and PS, whereas HIV/HCV coinfected recipients had worse outcomes. Although encouraging, these results suggest caution in transplanting coinfected patients.
Monozygotic twinning and IVF/ICSI treatment: a report of 11 cases and review of literature
Authors: N Abusheikha, O Salha, V Sharma, P Brinsden, N Abusheika
Journal: Human Reproduction Update (2000)

Monozygotic twinning is a relatively rare event in in-vivo conception, being estimated to occur in 0.42% of all births. The underlying mechanism for monozygotic twin formation is the division of the embryo early in its development. Separation of cells may theoretically occur before or after inner cell mass formation. In this analysis we report 11 cases of monozygotic twins resulting from IVF or intracytoplasmic sperm injection (ICSI) treatment cycles performed between 1991 and 1998 at St James's University Hospital, Leeds, and Bourn Hall Clinic, Cambridge, UK. Six cases (55%) followed treatment with ICSI and seven cases (64%) were in women aged > or = 35 years. This article also reviews the scientific literature discussing information pertaining to frequency, aetiology and potential complications of the monozygotic twinning phenomenon. We conclude that patients at risk of monozygotic twinning are those aged >35 years of age and those who had artificial opening in the zona pellucida by application of micromanipulation techniques. Women undergoing assisted conception treatment, particularly those with these two risk factors, must be informed of the low but definite risk of monozygotic twinning when counselled regarding the number of embryos to be transferred and chances of multiple births.
Impaired Platelet Production of Nitric Oxide Predicts Presence of Acute Coronary Syndromes
Authors: Jane E. Freedman, Brian Ting, Beth Hankin, Joseph Loscalzo, John F. Keaney, Joseph A. Vita
Journal: Circulation (1998)

Thrombus formation within a coronary vessel is the acute precipitating event in most acute coronary syndromes. Recently, constitutive nitric oxide synthase (cNOS) has been identified in human platelets, and platelet-derived nitric oxide has been shown to inhibit platelet recruitment after aggregation. However, its role in regulating platelet responses under normal or pathologic conditions has not yet been elucidated.We examined nitric oxide (NO) production by platelets isolated from 87 patients undergoing coronary angiography, 37 with stable angina and 50 with unstable angina or a myocardial infarction within 2 weeks. After stimulation with 5 micromol/L ADP, platelet aggregation and NO production were simultaneously measured with an NO-selective microelectrode adapted for use in a standard platelet aggregometer. Mean (+/-SEM) platelet-derived NO production was 1.78+/-0.36 pmol/10(8) and 0.26+/-0.05 pmol/10(8) platelets in coronary patients with stable angina and acute coronary syndromes, respectively (P=0. 0001). By logistic regression analysis, heparin treatment (odds ratio 6.6, CI 1.9 to 22.8, P=0.003), lower platelet-NO production (odds ratio 4.0, CI 1.3 to 11.5, P=0.01), and extent of atherosclerosis (odds ratio 1.5, CI 1.1 to 2.0, P=0.02) were independent predictors of an acute coronary syndrome. In the subset of patients with angiographic evidence of atherosclerosis (n=83), logistic regression demonstrated that platelet NO production (odds ratio 3.9, CI 1.3 to 11.1, P=0.01) and heparin treatment (odds ratio 6.4, CI 1.9 to 22.0, P=0.004) were independent predictors of an acute coronary syndrome, whereas extent of atherosclerosis was not.In summary, aggregating platelets from patients with acute coronary syndromes produce less NO. Since platelet aggregation and thrombus formation are implicated in unstable angina and myocardial infarction, impaired platelet-derived NO production may contribute to the development of acute coronary syndromes.
Genotypic variation in Pneumocystis jirovecii isolates in Britain
Authors: R F Miller
Journal: Thorax (2005)

Pneumocystis jirovecii is the cause of Pneumocystis pneumonia (PCP) in immunosuppressed humans. Asymptomatic colonisation with P jirovecii may occur in patients with minor immunosuppression or chronic lung disease. The aim of this study was to describe the molecular epidemiology of P jirovecii in Britain over a period of 12.5 years.Between January 1989 and July 2001 161 samples of P jirovecii were obtained from patients with PCP (n = 119), patients colonised by P jirovecii (n = 35), and from air spora (n = 6). Genotyping of samples was performed at the mitochondrial large subunit rRNA (mt LSU rRNA).Genotype 1 (38%) was the most frequently identified genotype: genotypes 2 (26.6%), 3 (20.3%), and 4 (5%) were less common. Mixed infection (more than one genotype) was identified in 10% of samples. While genotype 1 was the most frequently detected type in both patients with PCP and those colonised by P jirovecii (38% and 42%, respectively), these groups differed in the relatively lower rate of detection of genotype 4 (2% v 17%) and the higher detection of mixed infection in those with PCP (13% v 3%). Detection of specific genotypes of P jirovecii was associated with the patient's place of residence (p = 0.02). There was no association between specific genotypes and severity of PCP as measured by arterial oxygen tension (p = 0.3).The evidence of clustering of specific genotypes with patient's postcode of residence is consistent with the hypothesis of person to person transmission of P jirovecii via the airborne route. The lack of association between specific mt LSU rRNA genotypes and severity of PCP suggests that this locus is not implicated in the virulence of the organism.
Blood Transfusion in Obstetrics
Authors: G. J. Ryan
Journal: BMJ (1939)

The proposed function of intermediate filaments is to provide a cell type-specific structural framework that maintains cell shape and organelle distribution and mediates signal transduction through its connections with the plasma membrane and the nucleus. Vimentin is the intermediate filament protein expressed in B lymphocytes. Immunocytochemical analysis of the high salt-stable cytoskeletons from B cells stimulated with anti-Ig revealed an increased accumulation of vimentin in the cytoskeleton compared to nontreated controls. This increased accumulation of vimentin in the cytoskeleton was manifested by the organization of vimentin into extensive filamentous arrays (EFA) as viewed in the fluorescent microscope. In contrast to the effects of anti-Ig, activation of B cells with LPS did not induce the organization of vimentin into EFA. This suggested that signals unique to anti-Ig directed EFA formation. Immunocytochemical results were verified by biochemical analysis showing that vimentin was more abundant in isolated cytoskeletons from anti-Ig activated B cells, than cytoskeletons isolated from LPS-activated B cells. These observations established a relationship between increased content of vimentin in the cytoskeleton and the formation of EFA. By testing a wide variety of activating agents, we were able to correlate increased vimentin expression in the cytoskeleton to activating agents that cross-link membrane Ig. It appeared that treatment of B cells with LPS prohibited the induction of EFA by anti-Ig because cotreatment with both anti-Ig and LPS resulted in decreased vimentin accumulation in the cytoskeleton to a level less than that in resting cells. The significance of these results with regard to B cell biology is discussed.
Change in Prevalence of Hearing Loss in US Adolescents
Authors: Josef Shargorodsky, Sharon G Curhan, Gary C Curhan, Roland Eavey
Journal: JAMA (2010)

<h3>Context</h3>Hearing loss is common and, in young persons, can compromise social development, communication skills, and educational achievement.<h3>Objective</h3>To examine the current prevalence of hearing loss in US adolescents and determine whether it has changed over time.<h3>Design</h3>Cross-sectional analyses of US representative demographic and audiometric data from the 1988 through 1994 and 2005 through 2006 time periods.<h3>Setting</h3>The Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994, and NHANES 2005-2006.<h3>Participants</h3>NHANES III examined 2928 participants and NHANES 2005-2006 examined 1771 participants, aged 12 to 19 years.<h3>Main Outcome Measures</h3>We calculated the prevalence of hearing loss in participants aged 12 to 19 years after accounting for the complex survey design. Audiometrically determined hearing loss was categorized as either unilateral or bilateral for low frequency (0.5, 1, and 2 kHz) or high frequency (3, 4, 6, and 8 kHz), and as slight loss (&gt;15 to &lt;25 dB) or mild or greater loss (≥25 dB) according to hearing sensitivity in the worse ear. The prevalence of hearing loss from NHANES 2005-2006 was compared with the prevalence from NHANES III (1988-1994). We also examined the cross-sectional relations between several potential risk factors and hearing loss. Logistic regression was used to calculate multivariate adjusted odds ratios (ORs) and 95% confidence intervals (CIs).<h3>Results</h3>The prevalence of any hearing loss increased significantly from 14.9% (95% CI, 13.0%-16.9%) in 1988-1994 to 19.5% (95% CI, 15.2%-23.8%) in 2005-2006 (P = .02). In 2005-2006, hearing loss was more commonly unilateral (prevalence, 14.0%; 95% CI, 10.4%-17.6%, vs 11.1%; 95% CI, 9.5%-12.8% in 1988-1994; P = .005) and involved the high frequencies (prevalence, 16.4%; 95% CI, 13.2%-19.7%, vs 12.8%; 95% CI, 11.1%-14.5% in 1988-1994; P = .02). Individuals from families below the federal poverty threshold (prevalence, 23.6%; 95% CI, 18.5%-28.7%) had significantly higher odds of hearing loss (multivariate adjusted OR, 1.60; 95% CI, 1.10-2.32) than those above the threshold (prevalence, 18.4%; 95% CI, 13.6%-23.2%).<h3>Conclusion</h3>The prevalence of hearing loss among a sample of US adolescents aged 12 to 19 years was greater in 2005-2006 compared with 1988-1994.
Caspase-1α Is Down-regulated in Human Ovarian Cancer Cells and the Overexpression of Caspase-1α Induces Apoptosis
Authors: Qiang Feng, Peixiang Li, Clara Salamanca, David Huntsman, Peter C.K. Leung, Nelly Auersperg
Journal: Cancer Research (2005)

Abstract Caspase-1 plays a key role in the processing of cytokines and in the apoptosis of neurons and macrophages. Whether it also causes apoptosis of cancer cells has been unclear. In this study, we screened an array of apoptosis-related proteins in ovarian carcinoma cell lines and their tissue of origin, ovarian surface epithelium (OSE). Caspase-1α protein was abundant in OSE and in nontumorigenic OSE with extended but limited life spans (immortalized OSE), but was reduced in the cancer lines A2780 and OVCAR10. By Western blot and immunofluorescence, caspase-1α levels were greatly reduced in six of eight ovarian carcinoma lines compared with OSE. By real-time reverse transcription-PCR, steady-state transcripts of the CASP1 gene were proportional to protein levels. Caspase-1α overexpression caused significant apoptosis, but overexpression of a caspase-1α mutant without catalytic activity did not, confirming that the effect was caspase-1α–specific. Immunofluorescence of caspase-1α and terminal nucleotidyl transferase–mediated dUTP-X nick end labeling colocalization clearly established a link between apoptosis and caspase-1α expression. Caspase-9 and caspase-3 were activated in caspase-1α overexpressing A2780 cells, suggesting involvement of an intrinsic apoptotic pathway. Caspase-1α overexpression did not change the apoptotic effect of cisplatin in A2780 and OVCAR10 cells, suggesting that this agent activates a different pathway. Immunohistochemically, caspase-1 was lower in ovarian serous carcinomas than in OSE. Our study indicates, for the first time, that caspase-1α is proapoptotic in ovarian cancer cells, and raises the possibility that its down-regulation is one of the mechanisms which increase resistance to apoptosis in cancer cells.
1362 THE AVAILABILITY OF DIRECT ACTING ANTIVIRALS (DAA) IN 2012: A FRENCH MODEL-BASED ANALYSIS OF THE INCREASED NUMBER OF PATIENTS TREATED FOR CHRONIC HCV INFECTION
Authors: S. Deufflc-Burban, P. Mathurin, S. Pol, C. Larsen, F. Roudot-Thoraval, J.-C. Desenclos, D. Dhumeaux, Y. Yazdanpanah
Journal: Journal of Hepatology (2011)
Sendai virus-specific T cell clones. V. Induction of a virus-specific response by antiidiotypic antibodies directed against a T helper cell clone.
Authors: H C Ertl, E Homans, S Tournas, R W Finberg
Journal: The Journal of Experimental Medicine (1984)

We used an antiidiotypic antibody directed against a Sendai virus-specific T helper cell clone to stimulate an immune response in vivo. In addition, the antiidiotypic antibody induced T cells that mediated a delayed-type hypersensitivity (DTH) response in several different mouse strains. Induction of the DTH response by the antiidiotypic antibody, in contrast to the DTH responses induced by virus, demonstrated a remarkable lack of H-2 restriction.
Endothelin-1 inhibits the neuronal norepinephrine transporter in hearts of male rats
Authors: J BACKS, E BRESCH, M LUTZ, A KRISTEN, M HAASS
Journal: Cardiovascular Research (2005)

Endothelin-1 (ET-1) potentiates norepinephrine (NE)-induced contractile responses. An impairment of cardiac NE re-uptake by the neuronal NE transporter (NET) contributes to an increased NE net release in failing hearts. We hypothesized that both phenomena are caused by ET-1-mediated inhibition of NET.[3H]-NE-uptake, electrical field stimulation-evoked NE overflow and left ventricular contractility (LV-dp/dt(max)) were measured in isolated perfused rat hearts. NET density on cardiac plasma membranes was determined by [3H]-mazindol binding. Experimental heart failure in rats was induced by transverse aortic constriction (TAC).ET-1 inhibited cardiac [3H]-NE-uptake in a concentration- and time-dependent manner. The endothelin A receptor (ET(A)) antagonist BQ123 but not the endothelin B receptor (ET(B)) antagonist BQ788 abolished ET-1-induced reduction of [3H]-NE-uptake. Likewise, ET-1, but not the ET(B) agonist sarafotoxin S6c, enhanced the stimulated overflow of endogenous NE. In contrast, ET-1 inhibited the stimulated NE overflow during NET blockade (exocytotic NE release) via activation of ET(B). In isovolumically contracting healthy hearts, ET-1 potentiated the NE- but not isoprenaline-induced increase in LV-dp/dt(max). Since isoprenaline is not a NET substrate, the enhanced LV-dp/dt(max) response to NE thus depends on NET. In TAC rats, ET(A) antagonism by darusentan improved both impairment of cardiac [3H]-NE-uptake and reduction of [3H]-mazindol binding sites.ET-1 inhibits cardiac NE re-uptake via ET(A) but attenuates exocytotic NE release via ET(B), resulting in opposite effects on cardiac NE net release. In healthy hearts, ET(A)-mediated inhibition of NE re-uptake exceeds ET(B)-mediated silencing of NE release and potentiates the NE-induced increase in left ventricular contractility. In TAC rats, endogenous ET-1 impairs NE re-uptake and promotes sympathetic overstimulation of failing hearts.
Fluorodeoxyuridine Modulates Cellular Expression of the DNA Base Excision Repair Enzyme Uracil-DNA Glycosylase
Authors: Jennifer A. Fischer, Susan Muller-Weeks, Salvatore J. Caradonna
Journal: Cancer Research (2006)

Abstract The thymidylate synthase inhibitor 5-fluorouracil (5-FU) continues to play a pivotal role in the treatment of cancer. A downstream event of thymidylate synthase inhibition involves the induction of a self-defeating base excision repair process. With the depletion of TTP pools, there is also an increase in dUMP. Metabolism of dUMP to the triphosphate dUTP results in elevated pools of this atypical precursor for DNA synthesis. Under these conditions, there is a destructive cycle of dUMP incorporation into DNA, removal of uracil by the base excision repair enzyme uracil-DNA glycosylase (UDG), and reincorporation of dUMP during the synthesis phase of DNA repair. The end point is DNA strand breaks and loss of DNA integrity, which contributes to cell death. Evidence presented here indicates that both the nuclear and the mitochondrial isoforms of UDG are modulated by FdUrd (and 5-FU) treatment in certain cell lines but not in others. Modulation occurs at the transcriptional and post-translational levels. Under normal conditions, nUDG protein appears in G1 and is degraded during the S to G2 phase transition. The present study provides evidence that, in certain cell lines, FdUrd mediates an atypical turnover of nUDG. Additional data indicate that, for cell lines that do not down-regulate nUDG, small interfering RNA–mediated knockdown of nUDG significantly increases resistance to the cytotoxic effects of FdUrd. Results from these studies show that nUDG is an additional determinant in FdUrd-mediated cytotoxicity and bolster the notion that the self-defeating base excision repair pathway, instigated by elevated dUTP (FdUTP) pools, contributes to the cytotoxic consequences of 5-FU chemotherapy. (Cancer Res 2006; 66(17): 8829-37)
Fetal Microchimerism in Women with Breast Cancer
Authors: Vijayakrishna K. Gadi, J. Lee Nelson
Journal: Cancer Research (2007)

Abstract Fetal microchimerism (FMc) describes long-term persistence of small numbers of fetal-derived allogeneic cells in the mother. Although FMc has been implicated as a mechanism of autoimmune disease, it may confer a beneficial effect with immune surveillance of malignant cells. We hypothesized that allogeneic FMc imparts a protective effect against breast cancer. Two observations provided a rationale for the study hypothesis. First, allogeneic cells convey risk reduction for recurrent malignancy in hematopoietic cell transplantation. Second, reduced risk of breast cancer is well recognized among parous compared with nulliparous women. As an initial test of the hypothesis, we investigated 82 women, 35 with breast cancer and 47 who were healthy, for male DNA in peripheral blood, presumed from a prior pregnancy with a male fetus. The prevalence and levels of male DNA were determined by real-time quantitative PCR for the Y chromosome–specific gene DYS14 in DNA extracted from peripheral blood mononuclear cells. FMc was found significantly more often in healthy women than women with breast cancer (43% versus 14%, respectively). Considering the absence of FMc as a risk factor, the odds ratio was 4.4 [95% confidence intervals (95% CI), 1.34–16.99; P = 0.006]. Restricting analysis to women known to had given birth to a son, the odds ratio was 5.9 (95% CI, 1.26–6.69; P = 0.01). Our findings indicate that allogeneic FMc may contribute to reduction in risk of breast cancer. Further studies are indicated and, if confirmed, extended studies to examine whether allogeneic immune surveillance from FMc is deficient in women with breast cancer. [Cancer Res 2007;67(19):9035–8]
HLA-DRB1*04 may be a marker of severity in giant cell arteritis
Authors: M. A GONZALEZ-GAY
Journal: Annals of the Rheumatic Diseases (2000)

<h3>Abstract</h3> Identification of gene co-expression patterns (gene modules) is widely used for grouping functionally-related genes during transcriptomic data analysis. An organism-wide atlas of high quality fundamental gene modules would provide a powerful tool for unbiased detection of biological signals from gene expression data. Here, using a method of independent component analysis we call DEXICA, we have defined and optimized 209 modules that broadly represent transcriptional wiring of the key experimental organism <i>C. elegans</i>. Interrogation of these modules reveals processes that are activated in long-lived mutants in cases where traditional analyses of differentially-expressed genes fail to do so. Using this resource, users can easily identify active modules in their gene expression data and access detailed descriptions of each module. Additionally, we show that modules can inform the strength of the association between a gene and an annotation (e.g. GO term). Analysis of “module-weighted annotations” improves on several aspects of traditional annotation-enrichment tests and can aid in functional interpretation of poorly annotated genes. Interactive access to the resource is provided at http://genemodules.org/.