tbuckley/cabot-search huggingface dataset:
Hydrogen peroxide contrast echocardiography: quantification in vivo of myocardial risk area during coronary occlusion and of the necrotic area remaining after myocardial reperfusion.
Authors: A J Kemper, J E O'Boyle, C A Cohen, A Taylor, A F Parisi
Journal: Circulation (1984)

During sustained coronary occlusion in canine preparations, the extent of regions that fail to show contrast enhancement when imaged by supra-aortic hydrogen peroxide contrast echocardiography (SHPCE) has been shown to correlate well for single cross sections with the extent of malperfused myocardium "at risk" of infarction. In the present study, SHPCE was investigated as a means of determining the fraction of total left ventricular mass at risk during occlusion. Since necrotic tissue has low blood flow even when reperfused, we also investigated the potential of quantitating the extent of infarcted myocardium by measuring the extent of contrast defects seen with SHPCE performed during reperfusion. In 20 dogs the fraction of the left ventricle showing a contrast defect during coronary occlusion correlated well with the fraction of the left ventricular mass "at risk" by an autoradiographic technique (autoradiography = 0.83 echocardiography + 8.6%; r = .89, SEE = 4.5%). SHPCE was also performed after 3 hr of reperfusion following occlusions varying in duration from 60 to 150 min. The fraction of the ventricle showing a contrast defect during reperfusion predicted the infarcted portion of the left ventricle as shown by triphenyl tetrazolium chloride staining (% left ventricle infarcted = 0.81 echocardiography + 3.3%; r = .84, SEE = 5.3%). Observer variability for the fraction of the ventricle showing a contrast defect was excellent during both occlusion and reperfusion. The ratio of the left ventricular extent of contrast-negative regions during reperfusion and occlusion was used to calculate a necrosis-to-risk index in vivo that correlated relatively well with the myocardial necrosis-to-risk ratio determined morphologically (r = .77, SEE = 16%).(ABSTRACT TRUNCATED AT 250 WORDS)
A short-term controlled trial of an adjustable oral appliance for the treatment of mild to moderate obstructive sleep apnoea
Authors: K. A. Ferguson, T. Ono, A. A. Lowe, S. al-Majed, L. L. Love, J. A. Fleetham
Journal: Thorax (1997)

BACKGROUND: Although oral appliances are effective in some patients with obstructive sleep apnoea (OSA), they are not universally effective. A novel anterior mandibular positioner (AMP) has been developed with an adjustable hinge that allows progressive advancement of the mandible. The objective of this prospective crossover study was to compare efficacy, side effects, patient compliance, and preference between AMP and nasal continuous positive airway pressure (nCPAP) in patients with symptomatic mild to moderate OSA. METHODS: Twenty four patients of mean (SD) age 44.0 (10.6) years were recruited with a mean (SD) body mass index of 32.0 (8.2) kg/m2, Epworth sleepiness score 10.7 (3.4), and apnoea/hypopnoea index 26.8 (11.9)/hour. There was a two week wash-in and a two week wash-out period and two treatment periods (AMP and nCPAP) each of four months. Efficacy, side effects, compliance, and preference were evaluated by a questionnaire and home sleep monitoring. RESULTS: One patient dropped out early in the study and three refused to cross over so treatment results are presented on the remaining 20 patients. The apnoea/hypopnoea index (AHI) was lower with nasal CPAP 4.2 (2.2)/hour than with the AMP 13.6 (14.5)/hour (p &lt; 0.01). Eleven of the 20 patients (55%) who used the AMP were treatment successes (reduction of AHI to &lt; 10/hour and relief of symptoms), one (5%) was a compliance failure (unable or unwilling to use the treatment), and eight (40%) were treatment failures (failure to reduce AHI to &lt; 10/hour and/or failure to relieve symptoms). Fourteen of the 20 patients (70%) who used nCPAP were treatment successes, six (30%) were compliance failures, and there were no treatment failures. There was greater patient satisfaction with the AMP (p &lt; 0.01) than with nCPAP but no difference in reported side effects or compliance. CONCLUSIONS: AMP is an effective treatment in some patients with mild to moderate OSA and is associated with greater patient satisfaction than nCPAP.
A human equivalent of mouse B-1 cells?
Authors: Marc Descatoire, Jean-Claude Weill, Claude-Agnès Reynaud, Sandra Weller
Journal: The Journal of Experimental Medicine (2011)

To the Editor: 

In a recent issue of The Journal of Experimental Medicine , [Thomas Rothstein and colleagues][1], a group with long-standing expertise in the field of mouse B1 cells, reported the description of a B1 B cell subset in human blood, a population that has thus far eluded identification
A 67-year-old woman with fever, multiple lung opacities, visual impairment and acute respiratory failure
Authors: Leticia Barbosa Kawano-Dourado, Alexandre de Melo Kawassaki, Vera Luiza Capelozzi, Marcos Soares Tavares, Carmen Sílvia Valente Barbas
Journal: Thorax (2011)

population-based preventive strategies for targeting the relevant molecular pathways. FUTURE STUDIESEvidence from other complex traits suggests that, with larger sample sizes, GWAS will reveal many more loci harbouring common sequence variants underlying respiratory diseases.Other studies will usefully focus on the role of rare sequence variants and structural genomic variants in respiratory disease.Understanding precisely how the molecular pathways highlighted by these genetic studies influence the development and progression of disease, and how they can be modified, provides a major challenge for the coming decade.
Normal regulation of calcitriol production in Gy mice. Evidence for biochemical heterogeneity in the X-linked hypophosphatemic diseases.
Authors: G A Davidai, T Nesbitt, M K Drezner
Journal: Journal of Clinical Investigation (1990)

Phenotypic heterogeneity in X-linked hypophosphatemic rickets (XLH) is ascribed to variable penetrance of the genetic abnormality. However, studies of hypophosphatemic (Hyp) and gyrorotary (Gy) mice indicate that mutations at different loci along the X chromosome may underlie the genetically transmitted hypophosphatemic disorders. Thus, genetic heterogeneity may be a determinant of the phenotypic variability in XLH. To determine if such variance includes biochemical diversity, we examined whether Gy mice, similar to Hyp mice, exhibit abnormal regulation of renal 25-hydroxyvitamin D (25[OH]D)-1 alpha-hydroxylase. Serum phosphorus in Gy (4.7 +/- 0.3 mg/dl) and phosphate (P)-depleted mice (4.9 +/- 0.4) was significantly less than normal (8.4 +/- 0.5). Consistent with P depletion, the Gy mice exhibited enhanced renal 25(OH)D-1 alpha-hydroxylase activity (9.3 +/- 0.6 fmol/mg kidney per min), similar to that of P-depleted normals (9.1 +/- 1.5), but significantly greater than that of controls (3.1 +/- 0.3). Such normal enzyme responsiveness was confirmed upon PTH stimulation (1 IU/h s.c.), which revealed that Gy mice increased renal 1-hydroxylase (59 +/- 7.7) similarly to normals (65 +/- 7.7) and P-depleted animals (58.4 +/- 7.8). Calcitonin administration also enhanced enzyme function comparably in the animal models. Evidence confirming normally responsive calcitriol production in untreated Gy mice included increased serum 1,25-dihydroxyvitamin D levels, gastrointestinal calcium absorption, and urinary calcium. The normally regulated vitamin D metabolism in Gy mice indicates that biochemically diverse disease may result from mutations in the gene family regulating renal P transport and underlying X-linked hypophosphatemia. We suspect such heterogeneity is due to altered P transport at variable segments of the proximal convoluted tubule.
The molecular basis of sperm-oocyte membrane interactions during mammalian fertilization
Authors: Janice P Evans
Journal: Human Reproduction Update (2002)

Gamete membrane interactions begin with adhesion (binding) of the sperm to the oocyte plasma membrane and culminate with fusion of the membranes of the gametes, thus creating the zygote through the union of these two very different cells. This review summarizes the molecular and cell biology of the cell-cell interactions between mammalian gametes. Recent research studies have provided new insights into the complexity of these interactions and into the importance of multimeric molecular networks and optimal membrane order in both sperm and oocytes for successful fertilization. Molecules that will be highlighted include cysteine-rich secretory protein 1 (CRISP1) and ADAMs [fertilin alpha (ADAM1), fertilin beta (ADAM2) and cyritestin (ADAM3)] on sperm, and integrins, CD9, and other integrin-associated proteins on oocytes, as well as other molecules. The characteristics of these gamete molecules are summarized, followed by discussions of the experimental data that provide evidence for their participation in gamete membrane interactions, and also of the specific roles that these molecules might play. Insights from a variety of research areas, including gamete biology, cell adhesion, and membrane fusion, are put together for a tentative model of how sperm-oocyte adhesion and fusion occur. The clinical relevance of correct gamete membrane interactions is also noted.
Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn's disease
Authors: F Costa
Journal: Gut (2005)

<b>Background and aims:</b> The clinical course of inflammatory bowel disease is characterised by a succession of relapses and remissions. The aim of our study was to assess whether the predictive value of faecal calprotectin—a non-invasive marker of intestinal inflammation—for clinical relapse is different in ulcerative colitis (UC) and Crohn's disease (CD). <b>Methods:</b> Seventy nine consecutive patients with a diagnosis of clinically quiescent inflammatory bowel disease (38 CD and 41 UC) were followed for 12 months, undergoing regular clinical evaluations and blood tests. A single stool sample was collected at the beginning of the study from each patient and the calprotectin concentration was assessed by a commercially available enzyme linked immunoassay. <b>Results:</b> In CD, median calprotectin values were 220.1 μg/g (95% confidence interval (CI) 21.7–418.5) in those patients who relapsed during follow up, and 220.5 μg/g (95% CI 53–388) in non-relapsing patients (p = 0.395). In UC, median calprotectin values were 220.6 μg/g (95% CI 86–355.2) and 67 μg/g (95% CI 15–119) in relapsing and non-relapsing patients, respectively (p&lt;0.0001). The multivariate Cox (proportional hazard) regression model, after adjustment for possible confounding variables, showed a twofold and 14-fold increase in the relapse risk, respectively, in those patients with CD and UC in clinical remission who had a faecal calprotectin concentration higher than 150 μg/g. <b>Conclusions:</b> Faecal calprotectin proved to be an even stronger predictor of clinical relapse in UC than in CD, which makes the test a promising non-invasive tool for monitoring and optimising therapy.
Different epitope structures select distinct mutant forms of an antibody variable region for expression during the immune response.
Authors: S Fish, M Fleming, J Sharon, T Manser
Journal: The Journal of Experimental Medicine (1991)

Antibody variable (V) regions that initially differ from one another by only single amino acid residues at VH-D and D-JH segment junctions (termed canonical V regions) can be elicited in strain A/J mice by three different haptens. Among such V regions an amino acid substitution due to somatic mutation is recurrently observed at VH CDR2 position 58, regardless of which of these haptens is used for immunization. This substitution confers upon a canonical V region a generic increase in affinity for all the haptens. Conversely, the type of amino acid substitution at VH position 59 resulting from somatic mutation that is recurrently observed among such V regions changes with the eliciting hapten, in a manner that correlates directly with the cognate affinity increases (or decreases) for hapten conferred by the observed substitutions. This small subregion of VH CDR2 therefore plays a major role in determining both affinity and specificity for antigen. The data confirm that affinity for antigen is of pivotal importance in determining the degree of selection of different mutant forms of a V region. Moreover, during an immune response a sufficiently diverse mutant repertoire can be generated from a single canonical V region to allow adaptation to increase affinity for three different epitopes.
Protein Tyrosine Phosphatases in Autoimmunity
Authors: Torkel Vang, Ana V. Miletic, Yutaka Arimura, Lutz Tautz, Robert C. Rickert, Tomas Mustelin
Journal: Annual Review of Immunology (2008)

Protein tyrosine phosphatases (PTPs) are important regulators of many cellular functions and a growing number of PTPs have been implicated in human disease conditions, such as developmental defects, neoplastic disorders, and immunodeficiency. Here, we review the involvement of PTPs in human autoimmunity. The leading examples include the allelic variant of the lymphoid tyrosine phosphatase (PTPN22), which is associated with multiple autoimmune diseases, and mutations that affect the exon-intron splicing of CD45 (PTPRC). We also find it likely that additional PTPs are involved in susceptibility to autoimmune and inflammatory diseases. Finally, we discuss the possibility that PTPs regulating the immune system may serve as therapeutic targets.
AN APPRAISAL OF THE PERSONALITY TYPES OF THE ADDICT
Authors: ROBERT H. FELIX
Journal: American Journal of Psychiatry (1944)

An attempt has been made to discuss addicts from the standpoint of types set up on the basis of manifestations of personality. It must be remembered, however, that any classification is of value only if it leads to better understanding the patient, which is essential to intelligent therapy. Indefinite or overlapping groupings not only serve no useful purpose, but may obstruct proper therapy. There is a danger in too much insistence on classification, since there is then a tendency to think of addicts in terms of groups or constellations rather than as individuals with individual personalities. At best the personalities of addicts in the same category are only similar; rarely can sweeping statements as to therapy be made on the basis of such groupings. The groups shade into one another and there will always be difficulty in classifying the borderline cases. This should cause us little concern from the therapeutic point of view since the patient should be treated according to the individual findings in any event. Finally, it should be noted that the personality types discussed are not peculiar to addicts alone. Except for normal individuals accidentally addicted, patients who have never used drugs can be found in any psychiatric clinic who would certainly fall into one or the other of the classes enumerated. The addict is not a creature apart from the psychiatric point of view. He differs from other psychiatric cases of the same class chiefly in his presenting symptom. The therapist must ever keep this fact before him, and treatment should be directed accordingly. This must be the first rule in treating the addict.
High Lipoprotein(a) Levels and Small Apolipoprotein(a) Size Prospectively Predict Cardiovascular Events in Dialysis Patients
Authors: Craig J. Longenecker, Michael J. Klag, Santica M. Marcovina, Yong-Mei Liu, Bernard G. Jaar, Neil R. Powe, Nancy E. Fink, Andrew S. Levey, Josef Coresh
Journal: Journal of the American Society of Nephrology (2005)

Lipoprotein(a) [Lp(a)] levels are increased in dialysis patients, suggesting that they may play a role in the elevated atherosclerotic cardiovascular disease (ASCVD) risk in this population. Few prospective studies of Lp(a) level, apolipoprotein(a) [apo(a)] size, and ASCVD have been performed in the dialysis population. An inception cohort of 833 incident dialysis patients were followed prospectively. Baseline Lp(a) was measured by apo(a) size-independent ELISA and apo(a) size by Western blot after SDS-agarose gel electrophoresis. A combined prospective nonfatal and fatal ASCVD end point included myocardial infarction, coronary revascularization, cerebrovascular accident, carotid endarterectomy, peripheral revascularization, gangrene, or limb amputation. Survival analyses were performed with adjustment for baseline demographics, comorbid conditions, ASCVD risk factors, albumin, lipids, and C-reactive protein. Median follow-up was 27.4 mo, with 297 ASCVD events, 130 non-ASCVD deaths, and seven losses to follow-up over 1649 person-years. In multivariate Cox regression models, both high Lp(a) concentration (>/=53 nmol/L) and low molecular weight (LMW) apo(a) isoforms (</=22 Kringle-IV repeats) predicted ASCVD events (relative hazard [RH] = 1.38, P = 0.02; RH = 1.58, P < 0.0005, respectively). In models that included both Lp(a) concentration and apo(a) size, only apo(a) size remained associated with ASCVD. Among those with both LMW apo(a) and Lp(a) level >123 nmol/L, the relative hazard (RH) of ASCVD was 1.73 (P < 0.0005), compared with high molecular weight apo(a) and Lp(a) level <123 nmol/L. No interactions by age, race, gender, diabetes, or ASCVD were present. Both LMW apo(a) size and high Lp(a) level predict ASCVD risk in dialysis patients, but the association of ASCVD with LMW isoforms is stronger than the association with high Lp(a) concentration.
A pilot open trial evaluating the efficacy of low-dose aminopterin in the canine homologue of human atopic dermatitis
Authors: T. Olivry, J.S. Paps, P. Bizikova, K.M. Murphy, H.A. Jackson, J. Zebala
Journal: British Journal of Dermatology (2007)

Journal Article A pilot open trial evaluating the efficacy of low‐dose aminopterin in the canine homologue of human atopic dermatitis Get access T. Olivry, T. Olivry Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, U.S.A.Allergy Core, Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar J.S. Paps, J.S. Paps Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar P. Bizikova, P. Bizikova Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar K.M. Murphy, K.M. Murphy Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar H.A. Jackson, H.A. Jackson Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar J. Zebala J. Zebala Syntrix Biosystems, Auburn, WA, U.S.A. E‐mail: Thierry_Olivry@ncsu.edu Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 157, Issue 5, 1 November 2007, Pages 1040–1042, https://doi.org/10.1111/j.1365-2133.2007.08133.x Published: 01 November 2007
A <i>Leishmania amazonensis</i> ZIP family iron transporter is essential for parasite replication within macrophage phagolysosomes
Authors: Chau Huynh, David L. Sacks, Norma W. Andrews
Journal: The Journal of Experimental Medicine (2006)

Infection of mammalian hosts with Leishmania amazonensis depends on the remarkable ability of these parasites to replicate within macrophage phagolysosomes. A critical adaptation for survival in this harsh environment is an efficient mechanism for gaining access to iron. In this study, we identify and characterize LIT1, a novel L. amazonensis membrane protein with extensive similarity to IRT1, a ZIP family ferrous iron transporter from Arabidopsis thaliana. The ability of LIT1 to promote iron transport was demonstrated after expression in yeast and in L. amazonensis LIT1-null amastigotes. Endogenous LIT1 was only detectable in amastigotes replicating intracellularly, and its intracellular expression was accelerated under conditions predicted to result in iron deprivation. Although L. amazonensis lacking LIT1 grew normally in axenic culture and had no defects differentiating into infective forms, replication within macrophages was abolished. Consistent with an essential role for LIT1 in intracellular growth as amastigotes, Δlit1 parasites were avirulent. After inoculation into highly susceptible mice, no lesions were detected, even after extensive periods of time. Despite the absence of pathology, viable Δlit1 parasites were recovered from the original sites of inoculation, indicating that L. amazonensis can persist in vivo independently of the ability to grow in macrophages. Our findings highlight the essential role played by intracellular iron acquisition in Leishmania virulence and identify this pathway as a promising target for therapeutic intervention.
Growth hormone treatment in growth-retarded adolescents after renal transplant
Authors: A.C.S. Hokken-Koelega, S.M.P.F. de Munck Keizer-Schrama, S.L.S. Drop, E.D. Wolff, T. Stijnen, M.A.J. de Ridder, M.C.J.W. de Jong, R.A. Donckerwolcke, J.W. Groothoff, W.F. Blum
Journal: The Lancet (1994)
Lung research funding in the UK: the British Lung Foundation perspective
Authors: W MACNEE, I M WALDEN
Journal: Thorax (1998)

The British Lung Foundation was launched in 1985 by a group of leading respiratory specialists to fund medical research into the prevention, treatment, alleviation, and cure of all lung diseases and to disseminate the useful results of this research. It remains the only charity supporting research throughout the UK into all aspects of lung disease and relies entirely on voluntary donations for this.

Although lung disease is the second largest cause of mortality in the UK, accounting for one in five deaths, its research funding attracts only 2% of government funding. The demand placed on the British Lung Foundation for research funding is substantial and is increasing every year.

Since 1985 the British Lung Foundation has committed over £10.8 million to research across the whole spectrum of lung diseases. These funds have been raised against strong competition for voluntary donations from other charitable causes, many of which are considered more fashionable and high profile. In terms of fund raising, lung disease is largely unseen. Despite these constraints, the Foundation is proud to have played a part in funding many …