tbuckley/cabot-search huggingface dataset:
Is there a biochemical basis for lower oesophageal sphincter (LOS) resting pressure?
Authors: G Zaninotto, L Dalla Libera, S Merigliano, E Ancona
Journal: Gut (1986)

Myosin plays a fundamental role in the contraction of muscle cells.Some structural differences of this protein are related to the different physical properties of muscle -that is, speed of shortening.The typical myosin protein has a molecular weight of 460 000 daltons and is made up of six subunits: two heavy chains (200 000 daltons each) and two pairs of light chains (LC) weighing 15 000-25 000 daltons each (LC1 and LC2).Myosin was extracted from six specimens of human oesophagus in order to find out whether any biochemical differences exist between the oesophageal body and the lower oesophageal sphincter, to account for their different properties.Myosin was examined by two dimensional gel electrophoresis.Peptide mapping of myosin heavy chains was obtained by carrying out enzymatic digestion during the electrophoretic run.A quantitative difference between LC1 of the oesophageal body and the lower oesophageal sphincter was found in the circular fibres, thereby suggesting that two populations of muscle fibres exist in the inner coat of the oesophagus.The presence of more than one type of myosin strongly implies functional differentiation of the two specialised zones.on August 17,
THE BACTERICIDAL ACTION OF SYNTHETIC DETERGENTS
Authors: Zelma Baker, R. W. Harrison, Benjamin F. Miller
Journal: The Journal of Experimental Medicine (1941)

1. The bactericidal action of a number of anionic and cationic synthetic detergents on four Gram-positive and three Gram-negative bacteria has been investigated. 2. Cationic detergents, as a group, were found to exhibit marked bactericidal effects on Gram-positive microorganisms and somewhat less pronounced action on Gram-negative organisms. 3. The anionic detergents were germicidal only against the Gram-positive organisms, and they were considerably less effective than the cationic compounds. Of the anionic detergents, the most active one was an alkyl sulfate derived from a branched-chain, secondary alcohol. 4. Correlations between bactericidal action and inhibition of bacterial metabolism, and also between bactericidal action and chemical structure of the detergents are discussed.
A Comparison of Postprandial and Preprandial Administration of Insulin Aspart in Children and Adolescents With Type 1 Diabetes
Authors: Thomas Danne, Jan Aman, Edith Schober, Dorothee Deiss, Judith L. Jacobsen, Hans Henrik Friberg, Lars Hein Jensen
Journal: Diabetes Care (2003)

The aim of this study was to compare the glycemic control of preprandial versus postprandial injections of the new rapid-acting insulin analogue aspart in children and adolescents with type 1 diabetes.Forty-two children (aged 6-12 years) and 34 adolescents (13-17 years) were randomized to preprandial (immediately before meal start) and postprandial (immediately after a meal or a maximum of 30 min after meal start) treatment with insulin aspart (at least thrice daily) as part of a basal/bolus regimen in a multicenter study with an open labeled, two-period cross-over design (6-week periods). Of this group, 49% were boys, 55% were aged <or=13 years, and duration of diabetes was 4.4 years (range 1.0-9.4).Glycemic control for postprandial treatment was not worse than preprandial treatment as assessed by fructosamine week 0 vs. 6 (mean +/- SD, preprandial 367 +/- 74 vs. 378 +/- 90 micro mol/l; postprandial 383 +/- 83 vs. 385 +/- 77 micro mol/l) and HbA(1c) (preprandial 7.9 +/- 1.3 vs. 8.0 +/- 1.5%; postprandial 8.0 +/- 1.4 vs. 8.3 +/- 1.5%, P = 0.14). The only statistically significant finding from the seven-point blood glucose profiles and derived parameters between preprandial and postprandial treatment was a lower postprandial glucose level 120 min after breakfast (mean +/- SEM, -2.08 +/- 0.74 mmol/l, P = 0.016). The relative risk of hypoglycemia (blood glucose <3.9 mmol/l) preprandially to postprandially was not significantly different (mean 1.1; 95% CI 0.91-1.35; P = 0.31). Overall treatment satisfaction was equally high for both regimens with both patients and parents.Although preprandial administration of insulin aspart is generally preferable, this study shows that in children and adolescents, postprandial administration of insulin aspart is a safe and effective alternative.
Antidepressants and heart disease
Authors: R Farmer, S A Montgomery
Journal: BMJ (1984)

Case 3-A 20 year old man had been treated with penicillamine for severe intention tremor and dysarthria.He responded well but later stopped his medication and his symptoms recurred.Treatment was restarted using penicillamine and zinc sulphate.After two weeks there was no improvement and he had developed severe vomiting.Zinc was stopped and he recovered completely over six months on penicillamine alone.Case 4-A 14 year old girl presented with severe dystonia, frequent painful muscular spasms, dysarthria, and dysphagia.Penicillamine rapidly induced a severe thrombocytopenia and had to be stopped.She was -treated for a year with trientine with no appreciable clinical improvement although the blood and urine copper concentrations im- proved satisfactorily.At the end of a year zinc acetate, 84 mg (50 mol Zn + +) three times a day, was added to her treatment.She made a slow but significant improvement.After six months she was able to attend a school for the physically handicapped although she still used a wheelchair.
A Locus for Adolescent and Adult Onset Familial Focal Segmental Glomerulosclerosis on Chromosome 1q25-31
Authors: HIROYASU TSUKAGUCHI, HENRY YAGER, JOHN DAWBORN, LUIS JOST, JERRY COHLMIA, PATRICIA F. ABREU, APARECIDO B. PEREIRA, MARTIN R. POLLAK
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Focal segmental glomerulosclerosis is a nonspecific renal lesion observed both as a primary (idiopathic) entity and in a secondary form, typically in association with reduced functional renal mass. Familial forms have been observed and two loci for autosomal dominant FSGS have been mapped. This study shows that an adolescent/adult form of recessive FSGS maps to a locus on chromosome 1q25-31, which overlaps with a region previously identified as harboring a locus for an early childhood onset recessive form of nephrotic syndrome ( SRN1 ). Evaluation of a large family demonstrated linkage with a maximum two-point lod score of 3.98 at D1S254 and D1S222 . Lod score calculations support the conclusion of linkage in four of five additional families. Haplotype analysis suggests that this FSGS gene is located in a 19-cM region flanked by D1S416 and D1S413 , of which 6 cM overlaps with SRN1 , suggesting that these distinct clinical subsets of kidney disease may be allelic. These regions may also overlap with the syntenic region of the glomerulosclerosis susceptibility locus in the BUF/Mna rat. Because the presentation of FSGS may be subtle, inherited FSGS may be much more common than generally realized and grossly underestimated because of the absence of clear familial patterns. This result increases the suspicion that polymorphisms at this locus may contribute to sporadic FSGS.
Systemic hypotension and diuresis byL-arginine in cirrhotic patients with ascites: Role of nitric oxide
Authors: Kazuo Tajiri, Happei Miyakawa, Namiki Izumi, Fumiaki Marumo, Chifumi Sato
Journal: Hepatology (1995)

To investigate the role of nitric oxide in renal function and hemodynamics in cirrhotic patients with ascites, L-arginine (30 g in 300 mL of distilled water), a substrate for nitric oxide synthase, was infused into six cirrhotic patients with ascites, and the effects were compared with those of saline infusion. Healthy controls (n = 5) were also studied under the same conditions. In the patients, L-arginine infusion significantly decreased systolic and diastolic blood pressures while markedly increasing urinary flow and urinary sodium excretion; no significant changes were seen with saline infusion. In controls, only diastolic blood pressure was decreased by L-arginine infusion, whereas urinary flow and urinary sodium excretion were increased by both L-arginine and saline infusion. In both groups, a similar increase of plasma atrial natriuretic factor (ANF) was seen with L-arginine and saline infusions; endothelin and catecholamines were not affected by either infusion. In both groups, plasma levels of vasopressin were increased by L-arginine infusion. In the cirrhotic patients, urinary excretions of cyclic guanosine monophosphate (cGMP) and nitrates/nitrites (NOx) were significantly increased by L-arginine infusion, whereas no significant changes were seen with saline infusion. In controls, only the excretion of cGMP was increased by L-arginine infusion. In summary, L-arginine infusion induces diuresis and natriuresis accompanied by increased excretions of cGMP and NOx in cirrhotic patients with ascites. This differs from the response in controls, where the increase in urinary sodium excretion is not accompanied by an increase in markers of increased nitric oxide synthesis.
APC-derived cytokines and T cell polarization in autoimmune inflammation
Authors: Ilona Gutcher, Burkhard Becher
Journal: Journal of Clinical Investigation (2007)

T cell–mediated autoimmune diseases such as multiple sclerosis and rheumatoid arthritis are driven by autoaggressive Th cells. The pathogenicity of such Th cells has, in the past, been considered to be dictated by their cytokine polarization profile. The polarization of such effector T cells relies critically upon the actions of cytokines secreted by APCs. While Th1 polarization has long been associated with the pathogenesis of autoimmune diseases, recent data obtained in gene-targeted mice and the discovery of Th17 cell involvement in autoimmunity conflict with this hypothesis. In light of these recent developments, we discuss in this review the actions of APC-derived cytokines and their emerging roles in T cell polarization in the context of autoimmune inflammatory responses.
Loss of Roquin induces early death and immune deregulation but not autoimmunity
Authors: Arianna Bertossi, Martin Aichinger, Paola Sansonetti, Maciej Lech, Frauke Neff, Martin Pal, F. Thomas Wunderlich, Hans-Joachim Anders, Ludger Klein, Marc Schmidt-Supprian
Journal: The Journal of Experimental Medicine (2011)

The substitution of one amino acid in the Roquin protein by the sanroque mutation induces a dramatic autoimmune syndrome in mice. This is believed to occur through ectopic expression of inducible T cell co-stimulator (ICOS) and unrestrained differentiation of follicular T helper cells, which induce spontaneous germinal center reactions to self-antigens. In this study, we demonstrate that tissue-specific ablation of Roquin in T or B cells, in the entire hematopoietic system, or in epithelial cells of transplanted thymi did not cause autoimmunity. Loss of Roquin induced elevated expression of ICOS through T cell–intrinsic and –extrinsic mechanisms, which itself was not sufficient to break self-tolerance. Instead, ablation of Roquin in the hematopoietic system caused defined changes in immune homeostasis, including the expansion of macrophages, eosinophils, and T cell subsets, most dramatically CD8 effector–like T cells, through cell-autonomous and nonautonomous mechanisms. Germline Roquin deficiency led to perinatal lethality, which was partially rescued on the genetic background of an outbred strain. However, not even complete absence of Roquin resulted in overt self-reactivity, suggesting that the sanroque mutation induces autoimmunity through an as yet unknown mechanism.
Treatment of multidrug-resistant pulmonary tuberculosis with interferon-γ via aerosol
Authors: Rany Condos, William N Rom, Neil W Schluger
Journal: The Lancet (1997)

Background Multidrug-resistant tuberculosis (MDR-TB) is associated with substantial morbidity, despite drug therapy. Interferon-γ, a cytokine produced mainly by CD4 T lymphocytes, can activate alveolar macrophages, important effector cells in host immunity against Mycobacterium tuberculosis. We investigated safety and tolerability of aerosolised interferon-γ in patients with MDR-TB, and assessed its efficacy in terms of sputum-smear grades. Methods We did an open-label trial of aerosol interferon-γ given to five patients with smears and cultures positive for pulmonary MDR-TB, despite documented adherence to therapy. The patients received aerosol interferon-γ 500 μg three times a week for 1 month. Safety and tolerability were assessed, and, as well as routine clinical assessments, sputum samples for smear and culture were collected at entry and weekly. Computed tomography scans of the chest were done at baseline and after therapy ended. Findings Interferon-γ was well tolerated by all patients. In all five, bodyweight stabilised or increased. Sputum acid-fast-bacillus smears became negative in all patients, and the time to positive culture increased (from 17 to 24 days, not significant), which suggested that the mycobacterial burden had decreased. The size of cavitary lesions was reduced in all patients, 2 months after treatment had ended. Interpretation Preliminary data suggest that aerosol interferon-γ is a well-tolerated treatment that may be useful as adjunctive therapy in patients with MDR-TB who are otherwise not responding well to therapy.
Circulating Methylated-<i>DCR2</i>Gene in Serum as an Indicator of Prognosis and Therapeutic Efficacy in Patients with<i>MYCN</i>Nonamplified Neuroblastoma
Authors: Shigeki Yagyu, Takahiro Gotoh, Tomoko Iehara, Mitsuru Miyachi, Yoshiki Katsumi, Satoko Tsubai-Shimizu, Ken Kikuchi, Shinichi Tamura, Kunihiko Tsuchiya, Toshihiko Imamura, Akiko Misawa-Furihata, Tohru Sugimoto, Tadashi Sawada, Hajime Hosoi
Journal: Clinical Cancer Research (2008)

Abstract Background: MYCN amplification (MNA) in neuroblastoma is a strong indicator of poor prognosis. However, some MYCN nonamplified (non-MNA) cases show poor outcomes, and examining the status of the gene requires an operation, which may have surgical complications. Therefore, a new marker is needed to identify cases of non-MNA neuroblastomas with poor prognoses using less risky procedures. Aberrant hypermethylation of the DCR2 promoter has recently been associated with rapidly progressing neuroblastoma. We aimed to develop a noninvasive DCR2 methylation assay for patients with neuroblastoma using serum DNA, which predominantly originates from tumor-released DNA. Methods: Using DNA-based real-time PCR, we simultaneously quantified a methylated-DCR2 specific sequence (M) and a reference sequence (R) located in the promoter region in serum DNA, and evaluated DCR2 methylation status as M/R ratios in 86 patients with neuroblastoma. Results: Serum DCR2 M/R ratios were strongly correlated with those in the tumor (r = 0.67; P = 0.002). DCR2 methylation was associated with stage both in the whole neuroblastoma group and in the non-MNA group (P &amp;lt; 0.001), and DCR2-methylated patients showed significantly poorer 5-year event-free survival in the whole neuroblastoma group (43% versus 84%; P &amp;lt; 0.001), especially in the non-MNA group (12% versus 96%;P &amp;lt; 0.001). Among five DCR2-methylated patients whose clinical courses were followed, serum M/R ratios were close to 0 in the patients in remission, whereas the ratios increased in patients who relapsed. Conclusions: Detection of methylated-DCR2 in serum DNA has promise as a noninvasive assay for predicting prognosis and therapeutic efficacy in neuroblastoma, especially in non-MNA cases. Furthermore, it might be a sensitive marker of tumor recurrence in DCR2-methylated cases.
Long-Term (5-Year) Effects of a Reduced-Fat Diet Intervention in Individuals With Glucose Intolerance
Authors: Boyd A. Swinburn, Patricia A. Metcalf, Sarah J. Ley
Journal: Diabetes Care (2001)

OBJECTIVE—To determine whether reducing dietary fat would reduce body weight and improve long-term glycemia in people with glucose intolerance. RESEARCH DESIGN AND METHODS—A 5-year follow-up of a 1-year randomized controlled trial of a reduced-fat ad libitum diet versus a usual diet. Participants with glucose intolerance (2-h blood glucose 7.0–11.0 mmol/l) were recruited from a Workforce Diabetes Survey. The group that was randomized to a reduced-fat diet participated in monthly small-group education sessions on reduced-fat eating for 1 year. Body weight and glucose tolerance were measured in 136 participants at baseline, 6 months, and 1 year (end of intervention), with follow-up at 2 years (n = 104), 3 years (n = 99), and 5 years (n = 103). RESULTS—Compared with the control group, weight decreased in the reduced-fat–diet group (P &amp;lt; 0.0001); the greatest difference was noted at 1 year (–3.3 kg), diminished at subsequent follow-up (−3.2 kg at 2 years and −1.6 kg at 3 years), and was no longer present by 5 years (1.1 kg). Glucose tolerance also improved in patients on the reduced-fat diet; a lower proportion had type 2 diabetes or impaired glucose tolerance at 1 year (47 vs. 67%, P &amp;lt; 0.05), but in subsequent years, there were no differences between groups. However, the more compliant 50% of the intervention group maintained lower fasting and 2-h glucose at 5 years (P = 0.041 and P = 0.026, respectively) compared with control subjects. CONCLUSIONS—The natural history for people at high risk of developing type 2 diabetes is weight gain and deterioration in glucose tolerance. This process may be ameliorated through adherence to a reduced fat intake.
GeoSentinel Surveillance of Illness in Returned Travelers, 2007–2011
Authors: Karin Leder
Journal: Annals of Internal Medicine (2013)

Chinese translation Background: International travel continues to increase, particularly to Asia and Africa. Clinicians are increasingly likely to be consulted for advice before travel or by ill returned travelers. Objective: To describe typical diseases in returned travelers according to region, travel reason, and patient demographic characteristics; describe the pattern of low-frequency travel-associated diseases; and refine key messages for care before and after travel. Design: Descriptive, using GeoSentinel records. Setting: 53 tropical or travel disease units in 24 countries. Patients: 42 173 ill returned travelers seen between 2007 and 2011. Measurements: Frequencies of demographic characteristics, regions visited, and illnesses reported. Results: Asia (32.6%) and sub-Saharan Africa (26.7%) were the most common regions where illnesses were acquired. Three quarters of travel-related illness was due to gastrointestinal (34.0%), febrile (23.3%), and dermatologic (19.5%) diseases. Only 40.5% of all ill travelers reported pretravel medical visits. The relative frequency of many diseases varied with both travel destination and reason for travel, with travelers visiting friends and relatives in their country of origin having both a disproportionately high burden of serious febrile illness and very low rates of advice before travel (18.3%). Life-threatening diseases, such as Plasmodium falciparum malaria, melioidosis, and African trypanosomiasis, were reported. Limitations: Sentinel surveillance data collected by specialist clinics do not reflect healthy returning travelers or those with mild or self-limited illness. Data cannot be used to infer quantitative risk for illness. Conclusion: Many illnesses may have been preventable with appropriate advice, chemoprophylaxis, or vaccination. Clinicians can use these 5-year GeoSentinel data to help tailor more efficient pretravel preparation strategies and evaluate possible differential diagnoses of ill returned travelers according to destination and reason for travel. Primary Funding Source: Centers for Disease Control and Prevention.
Classification, Functions, and Clinical Relevance of Extracellular Vesicles
Authors: Edwin van der Pol, Anita N. Böing, Paul Harrison, Augueste Sturk, Rienk Nieuwland
Journal: Pharmacological Reviews (2012)

Both eukaryotic and prokaryotic cells release small, phospholipid-enclosed vesicles into their environment. Why do cells release vesicles? Initial studies showed that eukaryotic vesicles are used to remove obsolete cellular molecules. Although this release of vesicles is beneficial to the cell, the vesicles can also be a danger to their environment, for instance in blood, where vesicles can provide a surface supporting coagulation. Evidence is accumulating that vesicles are cargo containers used by eukaryotic cells to exchange biomolecules as transmembrane receptors and genetic information. Because also bacteria communicate to each other via extracellular vesicles, the intercellular communication via extracellular cargo carriers seems to be conserved throughout evolution, and therefore vesicles are likely to be a highly efficient, robust, and economic manner of exchanging information between cells. Furthermore, vesicles protect cells from accumulation of waste or drugs, they contribute to physiology and pathology, and they have a myriad of potential clinical applications, ranging from biomarkers to anticancer therapy. Because vesicles may pass the blood-brain barrier, they can perhaps even be considered naturally occurring liposomes. Unfortunately, pathways of vesicle release and vesicles themselves are also being used by tumors and infectious diseases to facilitate spreading, and to escape from immune surveillance. In this review, the different types, nomenclature, functions, and clinical relevance of vesicles will be discussed.
QUANTITATIVE ASPECTS OF IODINE METABOLISM IN MAN
Authors: DOUGLAS S. RIGGS
Journal: Pharmacological Reviews (1952)

It is perhaps appropriate that this review has ended with a consideration of the conversion ratio. Observation of the conversion ratio requires only the simplest chemical preparation of a sample of plasma, followed by two determinations of radioactivity. Its interpretation has required a rather complicated mathematical analysis, and even this has had to be based upon certain simplifyingassumptions not fully in accord with biological facts. It is easy for observation to outdistance precise interpretation.

Yet there is reason to be satisfied with the progress which has already been made towards an orderly arrangement of the observed facts into a solid foundation of quantitative theory. With so much to build upon, further progress should be rapid. In the reviewer's opinion, future advances are likely to stem chiefly from the simultaneous use of several techniques in the detailed investigation of small groups of patients. In particular, he would urge that studies with radioactive iodine be supplemented by the determination of stable iodine not only in blood but also in urine. Many of the present uncertainties concerning quantitative aspects of iodine metabolism in man might thereby be resolved.
Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort
Authors: Mikael Kuitunen, Kaarina Kukkonen, Kaisu Juntunen-Backman, Riitta Korpela, Tuija Poussa, Tuula Tuure, Tari Haahtela, Erkki Savilahti
Journal: Journal of Allergy and Clinical Immunology (2009)