tbuckley/cabot-search huggingface dataset:
Ciliary beat pattern is associated with specific ultrastructural defects in primary ciliary dyskinesia
Authors: M Chilvers
Journal: Journal of Allergy and Clinical Immunology (2003)

The main symptoms of primary ciliary dyskinesia (PCD) are nasal rhinorrhea or blockage and moist-sounding cough. Diagnosis can be difficult and is based on an abnormal ciliary beat frequency, accompanied by specific abnormalities of the ciliary axoneme. It is unknown whether determining ciliary beat pattern related to specific ultrastructural ciliary defects might help in the diagnosis of PCD.We sought to determine ciliary beat pattern and beat frequency (CBF) associated with the 5 common ultrastructural defects responsible for PCD.Nasal brushings were performed on 56 children with PCD. Ciliary movement was recorded using digital high-speed video imaging to assess beat frequency and pattern. Electron microscopy was performed.In patients with an isolated outer dynein arm or with an outer and inner dynein arm defect, 55% and 80% of cilia were immotile, respectively. Cilia that moved were only flickering. Mean CBF (+/- 95% CI) was 2.3 Hz (+/- 1.2) and 0.8 Hz(+/- 0.8), respectively. Cilia with an isolated inner dynein arm or a radial spoke defect had similar beat patterns. Cilia appeared stiff, had a reduced amplitude, and failed to bend along their length. Immotile cilia were present in 10% of cilia with an inner dynein arm defect and in 30% of radial spoke defects. Mean CBF was 9.3 Hz (+/- 2.6) and 6.0 Hz (+/- 3.1), respectively. The ciliary transposition defect produced a large circular beat pattern (mean CBF, 10.7 Hz [+/- 1.1]). No cilia were immotile.Different ultrastructural defects responsible for PCD result in predictable beat patterns. Recognition of these might help in the diagnostic evaluation of patients suspected of having PCD.
A Mouse Model of Renal Tubular Injury of Tyrosinemia Type 1
Authors: MAO-SEN SUN, SHINZABURO HATTORI, SHUJI KUBO, HISATAKA AWATA, ICHIRO MATSUDA, FUMIO ENDO
Journal: Journal of the American Society of Nephrology (2000)

Hereditary tyrosinemia type 1 (HT1) (McKusick 276700), a severe autosomal recessive disorder of tyrosine metabolism, is caused by mutations in the fumarylacetoacetate hydrolase gene Fah (EC 3.7.1.2), which encodes the last enzyme in the tyrosine catabolic pathway. HT1 is characterized by severe progressive liver disease and renal tubular dysfunction. Homozygous disruption of the gene encoding Fah in mice causes neonatal lethality (e.g., lethal Albino deletion c14CoS mice), an event that limits use of this animal as a model for HT1. A new mouse model was developed with two genetic defects, Fah and 4-hydroxyphenylpyruvate dioxygenase (Hpd). The Fah-/- Hpd-/- mice grew normally without evidence of liver and renal disease, and the phenotype is similar to that in Fah+/+ Hpd-/- mice. The renal tubular cells of Fah-/- Hpd-/- mice, particularly proximal tubular cells, underwent rapid apoptosis when homogentisate, the intermediate metabolite between HPD and FAH, was administered to the Fah-/- Hpd-/- mice. Simultaneously, renal tubular function was impaired and Fanconi syndrome occurred. Apoptotic death of renal tubular cells, but not renal dysfunction, was prevented by pretreatment of the animals with YVAD, a specific inhibitor of caspases. In the homogentisate-treated Fah-/- Hpd-/- mice, massive amounts of succinylacetone were excreted into the urine, regardless of treatment with inhibitors. It is suggested that apoptotic death of renal tubular cells, as induced by administration of homogentisate to Fah-/- Hpd-/- mice, was caused by an intrinsic process, and that renal apoptosis and tubular dysfunctions in tubular cells occurred through different pathways. These observations shed light on the pathogenesis of renal tubular injury in subjects with FAH deficiency. These Fah-/- Hpd-/- mice can serve as a model in experiments related to renal tubular damage.
Comparison of nutritional status in two systemic diseases involving respiratory system
Authors: Dominika Mekal, Emilia Swietlik, Anna Doboszynska
Journal: European Respiratory Journal (2013)

The study aimed at assessing and comparing nutritional status and life quality of patients with COPD and systemic scleroderma.  Material and Methods  Examined group included 30 patients with stable COPD and 32 patients with systemic scleroderma.  In all patients, the following parameters were measured: fat mass (FM), fat-free mass (FFM), total body water (TBW), and basal metabolic rate (BMR). Moreover, body mass index (BMI) and fat-free mass index (FFMI) were calculated. In all patients, spirometry and blood gases were measured. COPD patients’ life quality was assessed with St. George’s Respiratory Questionnaire (SGRQ), and in systemic scleroderma patients with SScQLI.  Results  In 13% of COPD patients a normal body weight was noted, in 60% obesity was diagnosed, 27% of patients were overweighed. In the systemic scleroderma, normal body weight was measured in 59%, overweight in 31%, obesity in one patient, and underweight in 2 patients. Mean BMI in COPD patients was 31.3, and 25.3 in patients with systemic scleroderma.  Mean score of the life quality was 57.3 in COPD patients and 35.8 in patients with systemic scleroderma.  Statistically significantly lower was life quality in COPD patients in comparison with systemic scleroderma patients. Mean value of FEV1 was 45.5 in COPD and 86.8 in the systemic scleroderma. In 58% COPD patients body weight significantly increased since the diagnosis, while in 45% of patients with systemic scleroderma remained unchanged. Conclusions  1. Nutritional disorders are more frequent in COPD patients in comparison with those with systemic scleroderma.  2. Life quality is statistically significantly worse in COPD patient that that in patients with systemic scleroderma.
Quantification of Cerebral Perfusion With “Real-Time” Contrast-Enhanced Ultrasound
Authors: Se-Joong Rim, Howard Leong-Poi, Jonathan R. Lindner, Daniel Couture, Dilantha Ellegala, Holland Mason, Marcel Durieux, Neal F. Kassel, Sanjiv Kaul
Journal: Circulation (2001)

No noninvasive technique is currently capable of "real-time" assessment and monitoring of cerebral blood flow (CBF). We hypothesized that cerebral perfusion could be accurately measured and monitored in "real time" with contrast-enhanced ultrasound (CEU).Cerebral perfusion was assessed in 9 dogs through a craniotomy with CEU at baseline and during hypercapnia and hypocapnia while normoxia was maintained. Cerebral microvascular blood volume (A), microbubble velocity (beta), and blood flow (Axbeta) were calculated from time-versus-acoustic intensity relations. Compared with baseline, hypercapnia and hypocapnia significantly increased and decreased CBF, respectively, as measured by CEU. These changes in blood flow were mediated by changes in both A and beta. A good correlation was found between Axbeta derived from CEU and CBF measured by radiolabeled microspheres (y=0.67x-0.04, r=0.91, P<0.001).Changes in both cerebral microvascular blood volume and red blood cell velocity can be accurately assessed with CEU. Thus, CEU has the potential for bedside measurement and monitoring of cerebral perfusion in real time in patients with craniotomies or burr holes.
Toxigenic Corynebacterium ulcerans infection in a veterinary student in London, United Kingdom, May 2010
Authors: J Taylor, M Saavedra-Campos, D Harwood, G Pritchard, N Raphaely, S Kapadia, A Efstratiou, J White, S Balasegaram
Journal: Eurosurveillance (2010)

We report on a case of toxigenic Corynebacterium ulcerans infection in a fully immunised veterinary student, investigated in London, United Kingdom, in May 2010. There was no ongoing transmission in human contacts. Possible animal sources were identified.
Selective Distal Splenorenal Shunt for Bleeding Esophageal Varices
Authors: R B Smith, W D Warren
Journal: Annual Review of Medicine (1975)

The selective distal splenorenal shunt has been shown to be equally as effective as total portal-systemic shunting procedures in the control of variceal hemorrhage and it can now be performed with an equivalent operative mortality. It is superior to other shunts in metabolic aspects and results in a markedly decreased incidence of postoperative hepatic encephalopathy. Massive ascites constitutes a definite contraindication to the selective distal splenorenal anastomosis, but for all other suitable patients this procedure appears to be the optimal method of surgical management at this time.
Elucidating the Basis of Airway Protection By Gastrointestinal Lactobacillus Johnsonii
Authors: Kaitlyn S. Lucey, Kei Fujimura, Marcus Rauch, Ali Faruqi, Douglas Fadrosh, Tine Demoor, Christine Cole Cole Johnson, Homer A. Boushey, Edward M. Zoratti, Dennis Ownby, Nicholas W. Lukacs, Susan V. Lynch
Journal: Journal of Allergy and Clinical Immunology (2014)
Toward a theory of human memory: Data structures and access processes
Authors: Michael S. Humphreys, Janet Wiles, Simon Dennis
Journal: Behavioral and Brain Sciences (1994)

Abstract Starting from Marr's ideas about levels of explanation, a theory of the data structures and access processes in human memory is demonstrated on 10 tasks. Functional characteristics of human memory are captured implementation-independently. Our theory generates a multidimensional task classification subsuming existing classifications such as the distinction between tasks that are implicit versus explicit, data driven versus conceptually driven, and simple associative (two-way bindings) versus higher order (threeway bindings), providing a broad basis for new experiments. The formal language clarifies the binding problem in episodic memory, the role of input pathways in both episodic and semantic (lexical) memory, the importance of the input set in episodic memory, and the ubiquitous calculation of an intersection in theories of episodic and lexical access.
Prevalence of permanent childhood hearing impairment in the United Kingdom and implications for universal neonatal hearing screening: questionnaire based ascertainment study Commentary: Universal newborn hearing screening: implications for coordinating and developing services for deaf and hearing impaired children
Authors: H. M Fortnum, A Q. Summerfield, D. H Marshall, A. C Davis, J. M Bamford, A. Davis, C. Yoshinaga-Itano, S. Hind
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To estimate the prevalence of confirmed permanent childhood hearing impairment and its profile across age and degree of impairment in the United Kingdom. <b>Design:</b> Retrospective total ascertainment through sources in the health and education sectors by postal questionnaire. <b>Setting:</b> Hospital based otology and audiology departments, community health clinics, education services for hearing impaired children. <b>Participants:</b> Children born from 1980 to 1995, resident in United Kingdom in 1998, with permanent childhood hearing impairment (hearing level in the better ear &gt;40 dB averaged over 0.5, 1, 2, and 4 kHz). <b>Main outcome measures:</b> Numbers of cases with date of birth and severity of impairment converted to prevalences for each annual birth cohort (cases/1000 live births) and adjusted for underascertainment. <b>Results:</b> 26 000 notifications ascertained 17 160 individual children. Prevalence rose from 0.91 (95% confidence interval 0.85 to 0.98) for 3 year olds to 1.65 (1.62 to 1.68) for children aged 9-16 years. Adjustment for underascertainment increased estimates to 1.07 (1.03 to 1.12) and 2.05 (2.02 to 2.08). Comparison with previous studies showed that prevalence increases with age, rather than declining with year of birth. <b>Conclusions:</b> Prevalence of confirmed permanent childhood hearing impairment increases until the age of 9 years to a level higher than previously estimated. Relative to current yields of universal neonatal hearing screening in the United Kingdom, which are close to 1/1000 live births, 50-90% more children are diagnosed with permanent childhood hearing impairment by the age of 9 years. Paediatric audiology services must have the capacity to achieve early identification and confirmation of these additional cases. <h3>What is already known on this topic</h3> The prevalence of confirmed permanent childhood hearing impairment (&gt;40 dB HL) in the United Kingdom has been estimated to rise with age to 1.33/1000 live births among children aged 5 years and older It has been predicted that only an additional 16% of children will remain to be detected in the postnatal years, given current yields from universal neonatal hearing screening <h3>What this study adds</h3> The prevalence of confirmed permanent childhood hearing impairment (&gt;40 dB HL) in the United Kingdom has risen with age to at least 1.65/1000 live births (and may be as high as 2.05/1000 live births) among children 9 years of age and older If the current yield from screening is sustained, then an additional 50-90% of children will remain to be detected in the postnatal years
Precursors of T cell growth factor producing cells in the thymus: ontogeny, frequency, and quantitative recovery in a subpopulation of phenotypically mature thymocytes defined by monoclonal antibody GK-1.5.
Authors: R Ceredig, D P Dialynas, F W Fitch, H R MacDonald
Journal: The Journal of Experimental Medicine (1983)

In this report, the ontogeny of precursors of T cell growth factor (TCGF)-producing cells in the mouse thymus was investigated using a recently described limiting dilution microculture system. In agreement with previous studies, in the adult thymus TCGF production by cells stimulated by alloantigens was largely the property of the Lyt-2-negative subpopulation. Furthermore, when Lyt-2-negative cells were stained with monoclonal antibody GK-1.5 and sorted according to fluorescence intensity, all precursors of TCGF-producing cells were quantitatively recovered in the GK-1.5-positive subpopulation. During ontogeny, TCGF production by Lyt-2-negative thymocytes was first detectable on the 19th day of embryonic development at which time the precursor frequency was 1/10th that found in the adult thymus. As in the adult thymus, all precursors of TCGF-producing cells had the GK-1.5-positive, Lyt-2-negative phenotype. In parallel to these functional studies, the ontogeny of GK-1.5+, Lyt-2- cells was investigated. In the adult thymus, 80% of cells expressed both GK-1.5 and Lyt-2 antigens, whereas minor subpopulations of 10% and 5% (corresponding to phenotypically mature thymocytes as defined by cortisone-resistant thymocytes [CRT]) expressed GK-1.5 or Lyt-2 exclusively; 3% of cells expressed neither antigen. During ontogeny, thymocytes expressing both GK-1.5 and Lyt-2 first appeared on the 16th day of embryonic development and their proportion increased rapidly thereafter. Interestingly, the GK-1.5+, Lyt-2- subpopulation first appeared in significant numbers on day 19 in parallel with the appearance of functional TCGF activity. Taken together with our previous studies correlating cytolytic T lymphocyte precursor (CTL-P) activity with the Lyt-2+, GK-1.5- subpopulation, these results further emphasize the strict correlation between functional activity and mature surface phenotype of both embryonic and adult thymocytes.
Effects of Atrial Premature Systoles on Sinus Rhythm in the Rabbit
Authors: HERMAN O. KLEIN, DONALD H. SINGER, BRIAN F. HOFFMAN
Journal: Circulation Research (1973)

Although it is well known that atrial premature depolarizations (APD s ) frequently lead to lengthening of the next cycle (returning cycle), it is usually not appreciated that shortening of the returning cycle (RC) can also occur. Moreover, the mechanism for these alterations is not clearly understood. APD s were therefore electrically induced in rabbit sinoatrial (SA) preparations, and four basic patterns of alteration in the SA nodal rhythm were observed. The type of change depended very much on the timing of the APD in the cycle. The atrial events, more often than not, failed to reflect the underlying SA nodal events. Thus, lengthened atrial RC s occurred in spite of shortened SA nodal RC s . This and other discrepancies indicate that the extracellular records of atrial activity do not faithfully reflect the events within the SA node and that information gathered from them should be interpreted with caution. Timing of the APD in the cycle, antegrade and retrograde SA conduction time, SA nodal action potential characteristics, and shifts in pacemaker sites are important in the determination of the altered SA nodal and atrial responses to APD s .
Randomised controlled trial of mesalazine in IBS
Authors: Giovanni Barbara, Cesare Cremon, Vito Annese, Guido Basilisco, Franco Bazzoli, Massimo Bellini, Antonio Benedetti, Luigi Benini, Fabrizio Bossa, Paola Buldrini, Michele Cicala, Rosario Cuomo, Bastianello Germanà, Paola Molteni, Matteo Neri, Marcello Rodi, Alfredo Saggioro, Maria Lia Scribano, Maurizio Vecchi, Giorgio Zoli, Roberto Corinaldesi, Vincenzo Stanghellini
Journal: Gut (2014)

<h3>Objective</h3> Low-grade intestinal inflammation plays a role in the pathophysiology of IBS. In this trial, we aimed at evaluating the efficacy and safety of mesalazine in patients with IBS. <h3>Design</h3> We conducted a phase 3, multicentre, tertiary setting, randomised, double-blind, placebo-controlled trial in patients with Rome III confirmed IBS. Patients were randomly assigned to either mesalazine, 800 mg, or placebo, three times daily for 12 weeks, and were followed for additional 12 weeks. The primary efficacy endpoint was satisfactory relief of abdominal pain/discomfort for at least half of the weeks of the treatment period. The key secondary endpoint was satisfactory relief of overall IBS symptoms. Supportive analyses were also performed classifying as responders patients with a percentage of affirmative answers of at least 75% or &gt;75% of time. <h3>Results</h3> A total of 185 patients with IBS were enrolled from 21 centres. For the primary endpoint, the responder patients were 68.6% in the mesalazine group versus 67.4% in the placebo group (p=0.870; 95% CI −12.8 to 15.1). In explorative analyses, with the 75% rule or &gt;75% rule, the percentage of responders was greater in the mesalazine group with a difference over placebo of 11.6% (p=0.115; 95% CI −2.7% to 26.0%) and 5.9% (p=0.404; 95% CI −7.8% to 19.4%), respectively, although these differences were not significant. For the key secondary endpoint, overall symptoms improved in the mesalazine group and reached a significant difference of 15.1% versus placebo (p=0.032; 95% CI 1.5% to 28.7%) with the &gt;75% rule. <h3>Conclusions</h3> Mesalazine treatment was not superior than placebo on the study primary endpoint. However, a subgroup of patients with IBS showed a sustained therapy response and benefits from a mesalazine therapy. <h3>Trial registration number</h3> ClincialTrials.gov number, NCT00626288.
Personalized Medicine in Cystic Fibrosis
Authors: John P. Clancy, Manu Jain
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Life expectancy in cystic fibrosis (CF) has improved substantially over the last 75 years, with a median predicted survival now approaching 40 years. This improvement has resulted largely from therapies treating end-organ manifestations. In an effort to develop drugs that would target the underlying defects in the CF transmembrane conductance regulator (CFTR), the Cystic Fibrosis Foundation embarked on a bold initiative in which it established collaborations with biopharmaceutical companies to support early-stage efforts to discover new medicines for CF. This has led to the development and clinical trial testing of several novel drugs targeting specific CFTR mutations. One drug, ivacaftor, was recently approved by the US Food and Drug Administration for the approximately 4% of patients with CF who have the G551D gating mutation. Drugs targeting F508del CFTR and premature termination codons, which would be applicable to 90% of patients with CF, are undergoing clinical trials. The impact of such drugs on CFTR biomarkers, such as sweat chloride and nasal potential difference, suggests that they may reset the clinical trajectory of CF, but their effect on long-term outcomes will remain unknown for many years. Nevertheless, development of CFTR-targeted drugs represents an important milestone in CF, perhaps revolutionizing the care of these patients in a fundamental way.
Cat allergen induces proinflammatory responses by human monocyte‐derived macrophages but not by dendritic cells
Authors: A.‐C. Andersson Lundell, H. Grindebacke, H. Karlsson, U. Seppälä, A. Rudin
Journal: Allergy (2005)

Background: The upper airway mucosa of healthy humans contains a dense network of cells with dendritic morphology of which the majority express a macrophage‐like phenotype (CD14+CD64+CD68+), whereas the smaller population are immature dendritic cells (DC; CD11c+CD14−). Our aim was to study the proinflammatory response of human monocytes and in vitro ‐generated macrophages and DC after contact with cat allergens. Methods: Monocyte‐derived DC and monocyte‐derived macrophages were exposed to cat allergen extract or Escherichia coli . Purified monocytes were stimulated with allergen extracts from cat or house dust mite (HDM) or the major allergenic protein Fel d 1 and induction of proinflammatory cytokines by monocytes was analyzed before and after blocking CD14. Results: We show that cat allergen extract induced tumor necrosis factor (TNF) and interleukin (IL)‐6 production by CD14‐positive macrophages but not by CD14‐negative DC. Moreover, monocytes produced significantly higher levels of TNF in response to cat allergens than in response to HDM allergens. We observed no differences in levels of TNF and IL‐6 from either macrophages or monocytes after exposure to cat allergen when comparing healthy and cat‐allergic individuals. Finally, the proinflammatory cytokine production from monocytes in response to cat allergen extract but not to HDM allergen was significantly reduced by blocking CD14. Conclusion: These results indicate that closely related innate immune cells from the myeloid lineage respond differentially to cat allergen extract and that the pattern‐recognition receptor CD14 might be one of the mediators involved in the inflammatory responses to inhalant allergens.
Tubular epithelial syndecan-1 maintains renal function in murine ischemia/reperfusion and human transplantation
Authors: Johanna W.A.M. Celie, Kiran K. Katta, Saritha Adepu, Wynand B.W.H. Melenhorst, Rogier M. Reijmers, Edith M. Slot, Robert H.J. Beelen, Marcel Spaargaren, Rutger J. Ploeg, Gerjan Navis, Jaap J. Homan van der Heide, Marcory C.R.F. van Dijk, Harry van Goor, Jacob van den Born
Journal: Kidney International (2012)