tbuckley/cabot-search huggingface dataset:
Lateral Gene Transfer and Gene Duplication Played a Key Role in the Evolution of Mastigamoeba balamuthi Hydrogenosomes
Authors: Eva Nývltová, Courtney W. Stairs, Ivan Hrdý, Jakub Rídl, Jan Mach, Jan Pačes, Andrew J. Roger, Jan Tachezy
Journal: Molecular Biology and Evolution (2015)

Lateral gene transfer (LGT) is an important mechanism of evolution for protists adapting to oxygen-poor environments. Specifically, modifications of energy metabolism in anaerobic forms of mitochondria (e.g., hydrogenosomes) are likely to have been associated with gene transfer from prokaryotes. An interesting question is whether the products of transferred genes were directly targeted into the ancestral organelle or initially operated in the cytosol and subsequently acquired organelle-targeting sequences. Here, we identified key enzymes of hydrogenosomal metabolism in the free-living anaerobic amoebozoan Mastigamoeba balamuthi and analyzed their cellular localizations, enzymatic activities, and evolutionary histories. Additionally, we characterized 1) several canonical mitochondrial components including respiratory complex II and the glycine cleavage system, 2) enzymes associated with anaerobic energy metabolism, including an unusual D-lactate dehydrogenase and acetyl CoA synthase, and 3) a sulfate activation pathway. Intriguingly, components of anaerobic energy metabolism are present in at least two gene copies. For each component, one copy possesses an mitochondrial targeting sequence (MTS), whereas the other lacks an MTS, yielding parallel cytosolic and hydrogenosomal extended glycolysis pathways. Experimentally, we confirmed that the organelle targeting of several proteins is fully dependent on the MTS. Phylogenetic analysis of all extended glycolysis components suggested that these components were acquired by LGT. We propose that the transformation from an ancestral organelle to a hydrogenosome in the M. balamuthi lineage involved the lateral acquisition of genes encoding extended glycolysis enzymes that initially operated in the cytosol and that established a parallel hydrogenosomal pathway after gene duplication and MTS acquisition.
Relationship between expression of IgA by Peyer's patch cells and functional IgA memory cells.
Authors: D A Lebman, P M Griffin, J J Cebra
Journal: The Journal of Experimental Medicine (1987)

IgA memory B cells have been operationally defined as precursors that give rise to clones exclusively secreting IgA antibodies upon antigen stimulation in a T-cell dependent splenic fragment culture. B lymphocytes that are sIgA+ account for a small fraction of Peyer's patch lymphocytes, but these can be clearly divided into two subsets. One subset contains the majority of sIgA+ B cells and most of these are in S, G2, or M phase of the cell cycle. These cells are germinal center B cells, as defined by being S kappa low and peanut agglutinin (PNA)high, and contain most of the mRNA alpha. Though these germinal center cells may contain the majority of sIgA+ B cells and may contain precursors for memory cells, preplasma cells, or both, they do not appear to be immediately responsive to stimulation by antigen. Rather, the S kappa high, PNAlow subset of sIgA+ B cells, most of which are in G0 or G1 and have only low levels of mRNA alpha appear to contain most of the clonal precursors that are committed to IgA, i.e., the functional memory cells that give rise to clones exclusively secreting IgA upon stimulation with thymus-dependent antigen in the presence of T cells. There is also a population of Peyer's patch B cells that neither bears detectable sIgA nor has mRNA alpha detectable by cytoplasmic dot blotting but contains a small proportion of the functional IgA memory cells.
Asthma prevalence in adults: good news?
Authors: S K Weiland
Journal: Thorax (2004)

Time trends in asthma prevalence may have levelled off

Few diseases have a relation to age which is as fascinating and complex as for asthma. It is a chronic but not necessarily lifelong condition. The incidence of asthma and wheezing illness peaks in very early childhood, but new incident cases occur throughout life.1–4 In many affected subjects, particularly children, it disappears after some time.2–4 However, in a substantial proportion of cases which have apparently lost the disease it will come back, often after many years.3,4 Another intriguing feature is that the sex ratio changes with age. Most studies show that boys are affected more often by wheezing illnesses than girls, but this sex ratio usually reverses during or shortly after puberty, partly due to a higher incidence in females.5–9

Most studies investigating the relationship between age and asthma have been performed in infants and children and, in fact, different age related phenotypes in childhood have been described which seem to have distinct causes and consequences.2,10 Information on the relation to age in adults is scarce and has often been based on routine data or cross sectional studies.1,6

In this issue of Thorax Chinn and colleagues report the findings of phase II of the European Community Respiratory Health Survey (ECRHS) which involved following more than 11 000 randomly selected adults (participants in ECRHS phase I stage 2 at which time they were aged 20–44 years) for a period of 5–11 …
Characteristics of Psychiatrists Who Perform ECT
Authors: R C Hermann, S L Ettner, R A Dorwart, C W Hoover, E Yeung
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: Use of ECT is highly variable, and previous study has linked its availability to the geographic concentration of psychiatrists. However, less than 8% of all U.S. psychiatrists provide ECT. The authors analyzed the characteristics of psychiatrists who use ECT to understand more fully the variation in its use and how changes in the psychiatric workforce may affect its availability. METHOD: Data from the 1988–1989 Professional Activities Survey were examined to investigate the influence of demographic, training, clinical practice, and geographic characteristics on whether psychiatrists use ECT. RESULTS: Psychiatrists who provided ECT were more likely to be male, to have graduated from a medical school outside the United States, and to have been trained in the 1960s or 1980s rather than the 1970s. They were more likely to provide medications than psychotherapy, to practice at private rather than state and county public hospitals, to treat patients with affective and organic disorders, and to practice in a county containing an academic medical center. CONCLUSIONS: Demographic and training characteristics significantly influence whether a psychiatrist uses ECT. Opposing trends in the U.S. psychiatric workforce could affect the availability of the procedure. Expanding training opportunities for ECT and making education, training, and testing more consistent nationwide could improve clinicians' consensus about ECT and narrow variation in its use. (Am J Psychiatry 1998; 155:889–894)
Validation and Utility of a Self-report Version of PRIME-MD&lt;SUBTITLE&gt;The PHQ Primary Care Study&lt;/SUBTITLE&gt;
Authors: Robert L. Spitzer
Journal: JAMA (1999)

The Primary Care Evaluation of Mental Disorders (PRIME-MD) was developed as a screening instrument but its administration time has limited its clinical usefulness.To determine if the self-administered PRIME-MD Patient Health Questionnaire (PHQ) has validity and utility for diagnosing mental disorders in primary care comparable to the original clinician-administered PRIME-MD.Criterion standard study undertaken between May 1997 and November 1998.Eight primary care clinics in the United States.Of a total of 3000 adult patients (selected by site-specific methods to avoid sampling bias) assessed by 62 primary care physicians (21 general internal medicine, 41 family practice), 585 patients had an interview with a mental health professional within 48 hours of completing the PHQ.Patient Health Questionnaire diagnoses compared with independent diagnoses made by mental health professionals; functional status measures; disability days; health care use; and treatment/referral decisions.A total of 825 (28%) of the 3000 individuals and 170 (29%) of the 585 had a PHQ diagnosis. There was good agreement between PHQ diagnoses and those of independent mental health professionals (for the diagnosis of any 1 or more PHQ disorder, kappa = 0.65; overall accuracy, 85%; sensitivity, 75%; specificity, 90%), similar to the original PRIME-MD. Patients with PHQ diagnoses had more functional impairment, disability days, and health care use than did patients without PHQ diagnoses (for all group main effects, P<.001). The average time required of the physician to review the PHQ was far less than to administer the original PRIME-MD (<3 minutes for 85% vs 16% of the cases). Although 80% of the physicians reported that routine use of the PHQ would be useful, new management actions were initiated or planned for only 117 (32%) of the 363 patients with 1 or more PHQ diagnoses not previously recognized.Our study suggests that the PHQ has diagnostic validity comparable to the original clinician-administered PRIME-MD, and is more efficient to use.
Montelukast improves symptoms of seasonal allergic rhinitis over a 4‐week treatment period
Authors: J. Van Adelsberg, G. Philip, A. J. Pedinoff, E. O. Meltzer, P. H. Ratner, J. Menten, T. F. Reiss
Journal: Allergy (2003)

Background: Proinflammatory mediators such as the cysteinyl leukotrienes are important in the pathophysiology of allergic rhinitis. This study evaluated the efficacy and tolerability of montelukast, a cysteinyl leukotriene receptor antagonist, given once daily in the morning for treatment of seasonal (fall) allergic rhinitis for 4 weeks. Methods: This was a randomized, double‐blind trial with a placebo run‐in and a 4‐week treatment period. Patients ( n = 1079) with a history of allergic rhinitis and a positive skin test to seasonal pollen allergens were assigned to placebo, montelukast 10 mg, or loratadine 10 mg. Symptoms were assessed with a daily diary. Results: Montelukast was more effective than placebo in improving scores for the primary endpoint of daytime nasal symptoms ( P = 0.003) and the secondary endpoints of night‐time, composite, and daytime eye symptoms, patient's and physician's global evaluations of allergic rhinitis, and rhinoconjunctivitis quality‐of‐life ( P ≤ 0.006). The positive control loratadine also improved scores for the primary endpoint ( P ≤ 0.001) and the majority of the secondary endpoints ( P &lt; 0.03). When analyzed by week, the treatment effect of montelukast was more persistent than loratadine over all 4 weeks of treatment. Conclusion: Montelukast provided effective relief of seasonal allergic rhinitis symptoms when given once daily in the morning, showed significant and sustained improvement in symptoms of allergic rhinitis over 4 weeks of treatment, and was well‐tolerated.
Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study
Authors: V Smith, J T Van Praet, B Vandooren, B Van der Cruyssen, J-M Naeyaert, S Decuman, D Elewaut, F De Keyser
Journal: Annals of the Rheumatic Diseases (2008)

Objectives: The safety and potential efficacy of rituximab was examined in diffuse cutaneous systemic sclerosis (dc-SSc). Methods: A 24 week open-label study in which eight patients with dc-SSc received an infusion of 1000 mg rituximab administered at baseline and day 15, together with 100 mg methylprednisolone at each infusion. Assessment included CD19+ peripheral blood lymphocyte number, skin sclerosis score, indices of internal organ functioning, the health assessment questionnaire disability index, the 36-item Short Form health survey and histopathological evaluation of the skin. Results: Ritixumab induced effective B-cell depletion in all patients (&lt;5 CD19+ cells/μl blood). There was a significant change in skin score at week 24 (p&lt;0.001). Also, significant improvements were measured in the dermal hyalinised collagen content (p = 0.014) and dermal myofibroblast numbers (p = 0.011). Two serious adverse events occurred, which were thought to be unrelated to the rituximab treatment. Conclusions: Rituximab appears to be well tolerated and may have potential efficacy for skin disease in dc-SSc. This study is registered with ClinicalTrials.gov, number NCT00379431.
Signal transducer and activator of transcription 3 activation is associated with bladder cancer cell growth and survival
Authors: Chun-Liang Chen, Ling Cen, Jennifer Kohout, Brian Hutzen, Christina Chan, Fu-Chuan Hsieh, Abbey Loy, Victor Huang, Gong Cheng, Jiayuh Lin
Journal: Molecular Cancer (2008)

Constitutive activation of signal transducer and activator of transcription 3 (Stat3) signaling pathway plays an important role in several human cancers. Activation of Stat3 is dependent on the phosphorylation at the tyrosine residue 705 by upstream kinases and subsequent nuclear translocation after dimerization. It remains unclear whether oncogenic Stat3 signaling pathway is involved in the oncogenesis of bladder cancer.We found that elevated Stat3 phosphorylation in 19 of 100 (19%) bladder cancer tissues as well as bladder cancer cell lines, WH, UMUC-3 and 253J. To explore whether Stat3 activation is associated with cell growth and survival of bladder cancer, we targeted the Stat3 signaling pathway in bladder cancer cells using an adenovirus-mediated dominant-negative Stat3 (Y705F) and a small molecule compound, STA-21. Both prohibited cell growth and induction of apoptosis in these bladder cancer cell lines but not in normal bladder smooth muscle cell (BdSMC). The survival inhibition might be mediated through apoptotic caspase 3, 8 and 9 pathways. Moreover, down-regulation of anti-apoptotic genes (Bcl-2, Bcl-xL and survivin) and a cell cycle regulating gene (cyclin D1) was associated with the cell growth inhibition and apoptosis.These results indicated that activation of Stat3 is crucial for bladder cancer cell growth and survival. Therefore, interference of Stat3 signaling pathway emerges as a potential therapeutic approach for bladder cancer.
Immunosuppressive Strategies that are Mediated by Tumor Cells
Authors: Gabriel A. Rabinovich, Dmitry Gabrilovich, Eduardo M. Sotomayor
Journal: Annual Review of Immunology (2006)

Despite major advances in understanding the mechanisms leading to tumor immunity, a number of obstacles hinder the successful translation of mechanistic insights into effective tumor immunotherapy. Such obstacles include the ability of tumors to foster a tolerant microenvironment and the activation of a plethora of immunosuppressive mechanisms, which may act in concert to counteract effective immune responses. Here we discuss different strategies employed by tumors to thwart immune responses, including tumor-induced impairment of antigen presentation, the activation of negative costimulatory signals, and the elaboration of immunosuppressive factors. In addition, we underscore the influence of regulatory cell populations that may contribute to this immunosuppressive network; these include regulatory T cells, natural killer T cells, and distinct subsets of immature and mature dendritic cells. The current wealth of preclinical information promises a future scenario in which the synchronized blockade of immunosuppressive mechanisms may be effective in combination with other conventional strategies to overcome immunological tolerance and promote tumor regression.
Serum amino terminal type III procollagen peptide and serum hyaluronan in rheumatoid arthritis: relation to clinical and serological parameters of inflammation during 8 and 24 months' treatment with levamisole, penicillamine, or azathioprine.
Authors: K Hørslev-Petersen, K.D Bentsen, A Engström-Laurent, P Junker, P Halberg, I Lorenzen
Journal: Annals of the Rheumatic Diseases (1988)

Increased serum levels of the amino terminal type III procollagen peptide and serum hyaluronan were demonstrated in patients with rheumatoid arthritis. In patients with active disease a significant correlation was shown between serum levels of the propeptide and hyaluronan and the clinical signs of synovitis reflecting the extent of synovial inflammation. During recovery the serum propeptide and serum hyaluronan showed a delayed decline as compared with the clinical signs of synovitis and the acute phase protein response. This probably reflects the presence of persistent subclinical chronic inflammation. Normal serum propeptide levels in rheumatoid arthritis were associated with a good prognosis without progression of erosive joint lesions. Azathioprine reduced the number of patients with progression of erosive joint lesions and caused a more marked suppression of the serum propeptide than levamisole and penicillamine.
Acidosis Downregulates Leptin Production from Cultured Adipocytes through a Glucose Transport-Dependent Post-transcriptional Mechanism
Authors: Daniel Teta, Alan Bevington, Jeremy Brown, Izabella Pawluczyk, Kevin Harris, John Walls
Journal: Journal of the American Society of Nephrology (2003)

Metabolic acidosis, a common feature of uremia, has a well documented wasting effect on skeletal muscle. In contrast, the effect of metabolic acidosis on adipose tissue is unknown. Serum levels of the adipocyte hormone leptin have been shown to be lower in acidotic uremic rats when compared with uremic controls. This study investigated the effect of acidosis on leptin protein secretion and leptin gene expression. This was studied in vitro by means of 3T3-L1 cultured adipocytes. Leptin secretion was decreased at an acid pH of 7.1 compared with a control pH of 7.5 (1277 versus 1950 pg/well/48 h, P < 0.05). In contrast, acidosis did not affect leptin mRNA content. Glucose transport was reduced by 39% at pH 7.1 at 24 h, which was comparable in magnitude with the inhibition of leptin secretion at the same pH. The glucose transport inhibitors cytochalasin B (0.5 to 50 micro M) and phloretin (0.05 to 0.25 mM) mimicked the effect of acidosis and reduced leptin secretion in a dose-dependent fashion (P < 0.02). Dose-response curves for the inhibition of glucose uptake showed that decreasing glucose transport to the same extent as with acid was sufficient to drive down leptin secretion, independently of changes of leptin mRNA. Acid decreases leptin secretion from 3T3-L1 adipocytes through a post-transcriptional mechanism via changes in glucose transport. This starvation-like response may be physiologically important in conditions such as uremia to prevent excessive energy expenditure.
Serum concentrations of C reactive protein, α<sub>1</sub>antitrypsin, and complement (C3, C4, C1 esterase inhibitor) before and during the Vuelta a Espańa
Authors: S J Semple, L L Smith, A J McKune, J Hoyos, B Mokgethwa, A F San Juan, A Lucia, A A Wadee
Journal: British Journal of Sports Medicine (2006)

Objectives: To determine serum concentrations of proinflammatory (C reactive protein, complement C3 and C4) and anti-inflammatory (α 1 antitrypsin, C1 esterase inhibitor (C1-INH)) acute phase proteins in elite cyclists before and during a three week cycle tour. Methods: Seventeen professional cyclists participating in the Vuelta a Espańa volunteered for the study. Their mean (SD) physical characteristics were: age 28 (1) years; height 1.7 (0.06) m; weight 65 (7) kg; body fat 7.6 (0.8)%; V o 2 max 75.3 (2.3) ml/kg/min. Venepuncture was performed on each subject 24 hours before the tour began (T0), on day 11 (the first rest day; T1) and day 21 (the second to last stage of the tour; T2). Samples at T1 and T2 were taken about 17 hours after the previous stage. Analysis of variance was used to determine changes over time. Where significance was found, a Tukey post hoc test was performed. Results: C reactive protein concentrations were consistently within the normal range, although there was a 228%, non-significant increase at T1. C3 concentrations fell within the normal range at all times assessed. C4 concentrations before the race were within the normal range and were significantly increased 10 days (T1) into the race. C1-INH concentrations did not change significantly throughout the race. α 1 Antitrypsin concentration before the race was at the lower end of the normal range and was only significantly raised at T2. Conclusions: Although not as pronounced as those reported in marathon/ultramarathon runners, elite cyclists participating in a three week cycle tour experienced increases in selected proinflammatory and anti-inflammatory acute phase proteins, indicating an acute phase/inflammatory response. It is tenable that the increase in α 1 antitrypsin and C1-INH (anti-inflammatory mediators) at T2 served to attenuate the acute phase/inflammatory response. The lower than normal resting concentrations of the acute phase proteins supports the notion that chronic aerobic exercise induces an anti-inflammatory state.
Bryan Moore-Smith
Authors: M. S. P. Phillips
Journal: BMJ (2013)

Leprosy is an infectious disease the principal clinical manifestations of which are anesthetic skin lesions and the development of peripheral neuropathy. The most common renal manifestation in leprosy patients is glomerulonephritis. Both immunofluorescent and electron microscopic studies suggest that the varied glomerular lesions found in these patients are immune complex mediated. Other renal lesions that have been described include amyloidosis, tubulointerstitial disease, acute renal failure, and functional defects in the absence of identifiable histologic abnormalities. In this report, a patient is described who developed the clinical syndrome of rapidly progressive glomerulonephritis. The renal biopsy showed a diffuse endocapillary proliferative process with electron-dense deposits in the glomerular subendothelial and subepithelial spaces. Organisms consistent with Mycobacterium leprae were identified within several of the glomeruli.
The concentration of hydrogen peroxide in exhaled air depends on expiratory flow rate
Authors: M.B. Schleiss, O. Holz, M. Behnke, K. Richter, H Magnussen, R.a Jorres
Journal: European Respiratory Journal (2000)

Hydrogen peroxide (H2O2) is known to be detectable in exhaled air. The present study aimed to determine whether the concentration of exhaled H2O2 depends on expiratory flow rate in order to make inferences on the site of its production within the lung. Breath condensate was collected in cooled Teflon tubes, at three different expiratorv flow rates, in 15 healthy or mild asthmatic subjects. Tests were repeated 2-5 times to assess reproducibility. Mean+/-SEM concentrations of H2O2 at flow rates of 140, 69 and 48 mL.s(-1) were 0.12+/-0.02, 0.19+/-0.02 and 0.32+/-0.03 microM, respectively. These values differed significantly from each other (p&lt;0.001). For comparison, average coefficients of variability within repeated measurements at each of the three flow rates were 68, 62 and 82%, respectively. These data demonstrate that the concentration of exhaled hydrogen peroxide depends on expiratory flow rate. Since flow dependence is an indicator of production within the airways, this result suggests that, to a large extent, the exhaled hydrogen peroxide originates within the airways. However, even under strictly controlled conditions, a high degree of variability persists, which may limit the usefulness of exhaled hydrogen peroxide as a marker of airway inflammation.
ON THE MURMURS OF THE HEART AND GREAT VESSELS
Authors: R. H. Powell
Journal: BMJ (1856)

a aeond examination, I detected another bag of mem- branes, and a second head presentation.On rupturing this bag, a second child was speedily born.On exploring the abdomen with my hand, I could detect another foetus in utero; consequently, I again made an examination per vaginam, and then discovered another bag of membranes entire, and transverse presentation.I then ruptured the membranes a second time, and turned the child.There was but one placenta, and that not an unusually large one.After a short labour of a few hours.the woman was safely delivered of three full grown male children.One lived twelve hours; another, twenty-four; and the last survived three days.This was the woman's first con- finement.