tbuckley/cabot-search huggingface dataset:
DISTORTION OF THE MALARIAL PARASITE. AN INTERPRETATION OF "PLASMODIUM TENUE" (STEPHENS.)
Authors: Mary R. Lawson
Journal: The Journal of Experimental Medicine (1916)

1. The correct interpretation of the form described by Stephens under the name of Plasmodium tenue is as follows: It is not a new species of parasite or an ameboid form, but a parasite attached to the external surface of red corpuscles and distorted by technique. 2. Evidence against a new species of parasite is: (a) they may be found in all known malarial infections and at any stage in the development of the parasite; and (b) they show evidence of distortion. 3. Evidence against ameboid forms and in favor of parasites distorted by technique is: (a) they may be found in but one of the two cover-slips prepared simultaneously; (b) they may be found in certain definite groups in various parts of a film which otherwise contains normal appearing parasites; (c) in rich infections, containing many disforted forms, they may be found in certain parts of a film, all distorted in one direction, the infected corpuscles and those adjacent to them showing no evidence of injury; and (d) two or more parasites attached to one red corpuscle may be seen to be distorted in one direction, or to have nuclei similarly distorted. 4. Three general types of distorted parasites may be recognized: (a) parasites with nuclei distorted and cytoplasm unaltered or but slightly distorted; (b) parasites with cytoplasm distorted and nuclei intact or but little disturbed; and (c) parasites with both nuclei and cytoplasm slightly or markedly distorted. 5. Red corpuscles to which distorted parasites are attached usually appear to be flattened out with slightly irregular outline, but parasites may be more or less distorted without any apparent change in the infected corpuscle. 6. Parasites with well stained chromatin and faded cytoplasm, or parasites with well stained cytoplasm and faded chromatin, may be found in specimens containing well stained parasites. It is usually possible to restain these specimens bringing out the faded cytoplasm belonging to the well stained chromatin or the lost chromatin belonging to the well stained cytoplasm.
Therapeutic Surgical Division of the Human Conduction System
Authors: Stanley Giannelli
Journal: JAMA (1967)

A 51-year-old woman was severely incapacitated because of intractable supraventricular tachycardias and rheumatic heart disease involving the aortic and mitral valves. The arrhythmias were not prevented by a variety of drug regimens, and over 200 cardioversions were done. It was believed that the arrhythmias had to be positively controlled if valvular surgery was to be successful. At open-heart surgery the aortic and mitral valves were replaced with ball-valve prostheses and the conduction bundle was divided in the region of the atrioventricular (AV) node. Permanent pacemaker leads were attached to the epicardium. Early postoperatively there was complete AV dissociation with a ventricular rate of 60 beats per minute. Later the ventricular rate slowed to 48 and a pacemaker was connected to the implanted leads for permanent ventricular pacing at 75 beats per minute.
Jab1/CSN5 Negatively Regulates p27 and Plays a Role in the Pathogenesis of Nasopharyngeal Carcinoma
Authors: Yunbao Pan, Qingxiu Zhang, Ling Tian, Xin Wang, Xiaohang Fan, Huizhong Zhang, Francois X. Claret, Huiling Yang
Journal: Cancer Research (2012)

Abstract Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus–associated malignancy most common in East Asia and Africa. Aberrant expression of Jab1/CSN5, a negative regulator of the cell-cycle inhibitor p27, is correlated with reduced p27 expression and associated with advanced tumor stage and poor prognosis in several human cancers. In this study, we examined the functional relationship between Jab1 and p27 protein expression in NPC. Immunohistochemical analysis showed an inverse association between Jab1 and p27 in NPC tissue samples, and overexpression of Jab1 correlated with poor survival in patients with NPC. Mechanistically, Jab1 and p27 were found to interact directly in NPC cells, with Jab1 mediating p27 degradation in a proteasome-dependent manner. Knockdown of Jab1 resulted in a remarkable increase in p27 levels and inhibition of cell proliferation, indicating that Jab1 targets p27 for degradation, thereby controlling its stability. Jab1 depletion also enhanced the antitumor effects of cisplatin in NPC cells. Together, our findings suggest that Jab1 overexpression plays an important role in the pathogenesis of NPC through Jab1-mediated p27 degradation. Jab1 therefore represents a novel diagnostic marker and therapeutic target in patients with NPC. Cancer Res; 72(7); 1890–900. ©2012 AACR.
Is sleep related to cancer in murine models of obstructive sleep disorder?
Authors: K.T. Nozoe, S. Tufik, M.L. Andersen
Journal: European Respiratory Journal (2012)

To the Editors:

The recent article by Almendros et al . [1] brings to light an interesting, but yet rarely discussed, relationship: the association between sleep disordered breathing and cancer. Overall, the study found that high-rate intermittent hypoxia (an animal model that mimics obstructive sleep apnoea) contributed to melanoma tumour growth in mice. There was an increase in the size and degree of necrosis, which were, on average, two times higher in mice exposed to intermittent hypoxia compared with the normoxia group. We would like to congratulate the authors for this study and emphasise the relevance of …
The role of inotropic variation in ventricular function during atrial fibrillation
Authors: Robert E. Edmands, Kalman Greenspan, Charles Fisch
Journal: Journal of Clinical Investigation (1970)

A series of experiments were performed upon intact anesthetized dogs to determine the relevance of a variety of hemodynamic variables to the irregular ventricular performance associated with atrial fibrillation. During experimentally induced atrial fibrillation central aortic pulse pressure was measured in relation to the duration of the preceding diastolic interval, the relative degree of cycle-length change, the magnitude of the preceding aortic end-diastolic pressure, the rate of ventricular tension development (at a fixed diastolic tension), and to ventricular end-diastolic pressure. While all of the latter variables bore a significant relation to the chosen parameters of ventricular function, the most linear correlation lay with the rate of ventricular tension development. It has been suggested, as a consequence, that the irregular ventricular performance observed during atrial fibrillation under these experimental conditions, may be more directly related to variation in the inotropic state of the ventricular myocardium than to an expression of the Frank-Starling concept, resulting from variable ventricular filling. The lability of the inotropic or contractile state has in turn been attributed to abrupt cycle-length change effecting inotropic alteration analogous to postextrasystolic potentiation of contractility and, at rapid rates, effecting an alternation of the contractile state.
Rapid drug susceptibility testing of Mycobacterium tuberculosis using conventional solid media
Authors: T Schaberg, B Reichert, T Schulin, H Lode, H Mauch
Journal: European Respiratory Journal (1995)

Radiometric methods for M. tuberculosis drug susceptibility testing yield much faster results than standard techniques; however, these methods require sophisticated equipment and are expensive. We investigated a rapid drug susceptibility testing method for isoniazid, rifampin, ethambutol, streptomycin and pyrazinamide in specimens from 197 patients with pulmonary tuberculosis using a simplified agar-dilution method. Middlebrook 7H11 agar solid medium and microcolony detection were used to test sputum from 64 smear-positive, and from 70 culture-positive but smear-negative patients. Culture-positive material from bronchoscopy, surgical biopsy, pleural fluid or gastric fluid of 63 patients was tested. In 64 smear-positive patients, the median time for final susceptibility results was 11 days (95% confidence interval (95% CI) 10-12 days) compared to 62 days (95% CI 56-66 days) with the standard method. In 133 smear-negative patients, results were available after a median of 35 days (95% CI 32-40 days) in contrast to 72 days (95% CI 62-83 days) with the standard method, regardless of whether or not sputum or other materials were used for primary culture. The rapid method detected all cases of single-drug resistance (n = 20) and multidrug resistance (n = 14) within 13 days (95% CI 9-17 days) in smear-positive patients (n = 8), or within 38 days (95% CI 35-48 days) in smear-negative patients (n = 26). Only one discrepancy was encountered in 985 resistance tests. Moreover, contamination was not observed. Our rapid susceptibility testing method for M. tuberculosis on Middlebrook 7H11 agar is fast, practical and inexpensive. It provides an alternative when more sophisticated techniques are not available or affordable.
Frataxin deficiency in pancreatic islets causes diabetes due to loss of β cell mass
Authors: Michael Ristow, Hindrik Mulder, Doreen Pomplun, Tim J. Schulz, Katrin Müller-Schmehl, Anja Krause, Malin Fex, Hélène Puccio, Jörg Müller, Frank Isken, Joachim Spranger, Dirk Müller-Wieland, Mark A. Magnuson, Matthias Möhlig, Michel Koenig, Andreas F.H. Pfeiffer
Journal: Journal of Clinical Investigation (2003)

Diabetes is caused by an absolute (type 1) or relative (type 2) deficiency of insulin-producing β cells. We have disrupted expression of the mitochondrial protein frataxin selectively in pancreatic β cells. Mice were born healthy but subsequently developed impaired glucose tolerance progressing to overt diabetes mellitus. These observations were explained by impairment of insulin secretion due to a loss of β cell mass in knockout animals. This phenotype was preceded by elevated levels of reactive oxygen species in knockout islets, an increased frequency of apoptosis, and a decreased number of proliferating β cells. Hence, disruption of the frataxin gene in pancreatic β cells causes diabetes following cellular growth arrest and apoptosis, paralleled by an increase in reactive oxygen species in islets. These observations might provide insight into the deterioration of β cell function observed in different subtypes of diabetes in humans.
Prevalence of Bronchial Hyperresponsiveness Among HIV-Infected Men
Authors: CHARLES D. POIRIER, NEIL INHABER, RICHARD G. LALONDE, PIERRE ERNST
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

HIV infection is associated with immune dysregulation primarily affecting T-cell function, whereas asthma is related to excessive T-cell activity. We compared the prevalence of asthma and related conditions among adult seropositive men with the prevalence among men of similar age drawn from the general population. Seropositive men had a significantly more frequent occurrence of wheezing (54.4 versus 21.2%), bronchial hyperresponsiveness (BHR) to methacholine (26.2 versus 14.4%), and an elevated total serum IgE (37.8 versus 25.7%). Differences in BHR were significant only among smokers. Among the seropositive men, FEV1/FVC and an elevated IgE were the principal determinants of BHR. Our results suggest that the frequency of asthma may be underestimated in HIV disease. Furthermore, the frequent occurrence of BHR in HIV-infected men who smoke (30.1%) suggests this group may be especially susceptible to the adverse effects of cigarette smoke.Keywords: asthma; HIV; airway disease; IgE; tobacco smoke
Relationship between Single Nucleotide Polymorphisms and Haplotypes in <i>DPYD</i> and Toxicity and Efficacy of Capecitabine in Advanced Colorectal Cancer
Authors: Maarten J. Deenen, Jolien Tol, Artur M Burylo, Valerie D. Doodeman, Anthonius de Boer, Andrew Vincent, Henk-Jan Guchelaar, Paul H.M. Smits, Jos H. Beijnen, Cornelis J.A. Punt, Jan H.M. Schellens, Annemieke Cats
Journal: Clinical Cancer Research (2011)

To explore the effect of dihydropyrimidine dehydrogenase (DPD) single nucleotide polymorphisms (SNP) and haplotypes on outcome of capecitabine.Germline DNA was available from 568 previously untreated patients with advanced colorectal cancer participating in the CAIRO2 trial, assigned to capecitabine, oxaliplatin, and bevacizumab ± cetuximab. The coding region of dihydropyrimidine dehydrogenase gene (DPYD) was sequenced in 45 cases with grade 3 or more capecitabine-related toxicity and in 100 randomly selected controls (cohort). Most discriminating (P < 0.1) or frequently occurring (>1%) nonsynonymous SNPs were analyzed in all 568 patients. SNPs and haplotypes were associated with toxicity, capecitabine dose modifications, and survival.A total of 29 SNPs were detected in the case-cohort analysis, of which 8 were analyzed in all 568 patients. Of the patients polymorphic for DPYD IVS14+1G>A, 2846A>T, and 1236G>A, 71% (5 of 7), 63% (5 of 8), and 50% (14 of 28) developed grade 3 to 4 diarrhea, respectively, compared with 24% in the overall population. All patients polymorphic for IVS14+1G>A developed any grade 3 to 4 toxicity, including one possibly capecitabine-related death. Because of toxicity, a mean capecitabine dose reduction of 50% was applied in IVS14+1G>A and 25% in 2846A>T variant allele carriers. Patients were categorized into six haplotype groups: one predicted for reduced (10%), and two for increased risks (41% and 33%) for severe diarrhea. Individual SNPs were not associated with overall survival, whereas one haplotype was associated with overall survival [HR (95% CI) = 0.57 (0.35-0.95)].DPYD IVS14+1G>A and 2846A>T predict for severe toxicity to capecitabine, for which patients require dose reductions. Haplotypes assist in selecting patients at risk for toxicity to capecitabine.
mTOR inhibition and levels of the DNA repair protein MGMT in T98G glioblastoma cells
Authors: Sarah Smalley, Anthony J Chalmers, Simon J Morley
Journal: Molecular Cancer (2014)

Glioblastoma multiforme (GBM), the most common and most aggressive type of primary adult brain tumour, responds poorly to conventional treatment. Temozolomide (TMZ) chemotherapy remains the most commonly used treatment, despite a large proportion of tumours displaying TMZ resistance. 60% of GBM tumours have unmethylated MGMT promoter regions, resulting in an overexpression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT), which is responsible for tumour resistance to TMZ chemotherapy. Tumours also often exhibit hyperactive PI3-kinase/mTOR signalling, which enables them to resynthesise proteins quickly. Since MGMT is a suicide protein that is degraded upon binding to and repairing TMZ-induced O6-methylguanine adducts, it has been hypothesized that inhibition of translation via the mTOR signalling pathway could generate a tumour-specific reduction in MGMT protein and increase TMZ sensitivity. MGMT was monitored at the post-transcriptional, translational and protein levels, to determine what effect mTOR inhibition was having on MGMT protein expression in vitro. We show that inhibiting mTOR signalling is indeed associated with acute inhibition of protein synthesis. Western blots show that despite this, relative to loading control proteins, steady state levels of MGMT protein increased and MGMT mRNA was retained in heavy polysomes. Whilst TMZ treatment resulted in maintained MGMT protein levels, concomitant treatment of T98G cells with TMZ and KU0063794 resulted in increased MGMT protein levels without changes in total mRNA levels. These in vitro data suggest that, counterintuitively, mTOR inhibition may not be a useful adjunct to TMZ therapy and that more investigation is needed before applying mTOR inhibitors in a clinical setting.
Rat diaphragm contractility and histopathology are affected differently by low dose treatment with methylprednisolone and deflazacort
Authors: P N Dekhuijzen, G Gayan-Ramirez, A Bisschop, V de Bock, R Dom, R Bouillon, M Decramer
Journal: European Respiratory Journal (1995)

The extent to which treatment with low doses of the nonfluorinated steroid methylprednisolone affects diaphragm contractility and morphology is unknown. In the present study, we compared the effects of equipotent doses of methylprednisolone and deflazacort, an oxazoline derivate of prednisolone with less systemic side-effects on bone structure and carbohydrate metabolism. Twenty six male adult rats were randomized to receive daily saline (control), methylprednisolone 0.4 mg.kg-1 or deflazacort 0.5 mg.kg-1 i.m. Contractile properties and histopathology were measured after a 6 week treatment period. During treatment, body weight increased in control and methylprednisolone-treated animals, but decreased by 4.2 +/- 1.1% (mean +/- SD) in the deflazacort group. Similarly, diaphragm mass in the deflazacort group was decreased compared to control and methylprednisolone groups. Twitch tension and twitch characteristics of isolated diaphragm bundles were similar in the three groups. Maximal tetanic tension was decreased in the deflazacort group. The force-frequency curve of the deflazacort bundles shifted downwards compared to control. Fatigue occurring during this protocol was greatest in the methylprednisolone- and deflazacort-treated animals. Microscopic examination revealed no gross abnormalities in the three groups. Histochemical analysis after staining for myosin adenosine triphosphatase (ATP-ase) showed that in the deflazacort group cross-sectional area of type I, IIa and IIb fibres were decreased. We conclude that low doses of methylprednisolone caused subtle and negligible changes in rat diaphragm contractile properties without affecting fibre dimensions, while deflazacort at an equipotent dose induced generalized fibre atrophy and changes in diaphragm contractility.
Imaging of pneumonia: trends and algorithms
Authors: T. Franquet
Journal: European Respiratory Journal (2001)

Pneumonia is one of the major infectious diseases responsible for significant morbidity and mortality throughout the world. Imaging plays a crucial role in the detection and management of patients with pneumonia. This review article discusses the different imaging methods used in the diagnosis and management of suspected pulmonary infections. The imaging examination should always begin with conventional radiography. When the results of routine radiography are inconclusive, computed tomography is mandatory. A combination of pattern recognition with knowledge of the clinical setting is the best approach to the pulmonary infectious processes. A specific pattern of involvement can suggest a likely diagnosis in many instances. In acquired immune deficiency syndrome patients, diffuse ground-glass and interstitial infiltrates are most commonly present in Pneumocystis carinii pneumonia whereas in the nonimmunosuppressed patients, a segmental lobar infiltrate is suggestive of a bacterial pneumonia. Round pneumonia is most often encountered in children than adults and is most often caused by Streptococcus pneumoniae . Different combinations of parenchymal and pleural abnormalities may be suggestive for additional diagnoses. When an infectious pulmonary process is suspected, knowledge of the varied radiographic manifestations will narrow the differential diagnosis, helping to direct additional diagnostic measures, and serving as an ideal tool for follow-up examinations.
Subunit Composition of Pre–T Cell Receptor Complexes Expressed by Primary Thymocytes: CD3δ Is Physically Associated but Not Functionally Required
Authors: Marc A. Berger, Vibhuti Davé, Michele R. Rhodes, Gayle C. Bosma, Melvin J. Bosma, Dietmar J. Kappes, David L. Wiest
Journal: The Journal of Experimental Medicine (1997)

Maturation of immature CD4−CD8− (DN) thymocytes to the CD4+CD8+ (DP) stage of development is driven by signals transduced through a pre–T cell receptor (TCR) complex, whose hallmark is a novel subunit termed pre-Tα (pTα). However, the precise role of pre-TCRs in mediating the DN to DP transition remains unclear. Moreover, progress in understanding pre-TCR function has been hampered thus far because previous attempts to demonstrate expression of pTα-containing pre-TCRs on the surface of normal thymocytes have been unsuccessful. In this report, we demonstrate for the first time that pTα-containing pre-TCR complexes are expressed at low levels on the surface of primary thymocytes and that these pre-TCR complexes comprise a disulfide-linked pTα–TCR-β heterodimer associated not only with CD3-γ and -ε, as previously reported, but also with ζ and δ. Interestingly, while CD3-δ is associated with the pre-TCR complex, it is not required for pre-TCR function, as evidenced by the generation of normal numbers of DP thymocytes in CD3-δ–deficient mice. The fact that any of the signaling components of the pre-TCR are dispensable for pre-TCR function is indeed surprising, given that few pre-TCR complexes are actually expressed on the surface of primary thymocytes in vivo. Thus, pre-TCRs do not require the full array of TCR-associated signaling subunits (γ, δ, ε, and ζ), possibly because pTα itself possesses signaling capabilities.
Urinary Paraben Concentrations and Ovarian Aging among Women from a Fertility Center
Authors: Kristen W. Smith, Irene Souter, Irene Dimitriadis, Shelley Ehrlich, Paige L. Williams, Antonia M. Calafat, Russ Hauser
Journal: Environmental Health Perspectives (2013)

Parabens are preservatives commonly used in personal care products, pharmaceuticals, and foods. There is documented widespread human exposure to parabens, and some experimental data suggest that they act as estrogenic endocrine disruptors. As far as we are aware, no epidemiologic studies have assessed female reproductive health effects in relation to paraben exposure.We examined the association of urinary paraben concentrations with markers of ovarian reserve in a prospective cohort study of women seeking fertility treatment at Massachusetts General Hospital, Boston, Massachusetts.Measures of ovarian reserve were day-3 follicle-stimulating hormone (FSH), antral follicle count (AFC), and ovarian volume. Paraben concentrations [methylparaben (MP), propylparaben (PP), and butylparaben (BP)] were measured in spot urine samples collected prior to the assessment of outcome measures. We used linear and Poisson regression models to estimate associations of urinary paraben concentrations (in tertiles) with ovarian reserve measures.Of the women enrolled in 2004-2010, 192 had at least one ovarian reserve outcome measured (mean age ± SD, 36.1 ± 4.5 years; range, 21.0-46.7 years). MP and PP were detected in > 99% of urine samples and BP in > 75%. We found a suggestive trend of lower AFC with increasing urinary PP tertiles [mean percent change (95% CI) for tertiles 2 and 3 compared with tertile 1, respectively, were -5.0% (-23.7, 18.4) and -16.3% (-30.8, 1.3); trend p-value (ptrend) = 0.07] as well as higher day-3 FSH with higher urinary PP tertiles [mean change (95% CI) for tertiles 2 and 3 compared with tertile 1 were 1.16 IU/L (-0.26, 2.57) and 1.02 IU/L (-0.40, 2.43); ptrend = 0.16]. We found no consistent evidence of associations between urinary MP or BP and day-3 FSH or AFC, or between urinary MP, PP, or BP and ovarian volume.PP may be associated with diminished ovarian reserve. However, our results require confirmation in further studies.