tbuckley/cabot-search huggingface dataset:
Immunological Aspects of Demyelinating Diseases
Authors: Roland Martin, Henry F. McFarland, Dale E. McFarlin
Journal: Annual Review of Immunology (1992)

Primary demyelination in the central nervous system results from damage to the myelin sheath or oligodendroglia and can be produced by a variety of mechanisms, including metabolic disturbances, toxicities, infection, and autoimmunity. The major human demyelinating disease affecting the central nervous system is multiple sclerosis (MS). Although the etiology of MS is not known, existing data indicate that both genetic and environmental factors contribute to pathogenesis. Experimental allergic encephalomyelitis (EAE) is induced by immunization of genetically susceptible animals with myelin proteins. This is mediated by autoimmune T cells. Characterization of MHC restriction, fine specificity of antigen recognition, and T cell receptor (TCR) usage by encephalitogenic T cells has resulted in highly specific immunotherapies. Both HLA and TCR genes have been linked to susceptibility for MS which is widely believed to be mediated by T cells that recognize an as yet unidentified autoantigen. Because of the advances in the understanding and treatment of EAE, recent research in MS has been focused on the characterization of cellular immune responses against myelin components. The results of these studies are reviewed and the potential implications of these findings for the pathogenesis and future therapy of MS are examined.
Angiotensin Converting Enzyme Genotype and Chronic Allograft Nephropathy in Protocol Biopsies
Authors: Miguel Hueso, Pedro Alía, Francesc Moreso, Violeta Beltrán-Sastre, Luis Riera, Carlota González, Miguel Ángel Navarro, Josep Maria Grinyó, Estanis Navarro, Daniel Serón
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Genotype DD of the angiotensin-converting enzyme (ACE) is not associated with an increased incidence of native renal diseases, although it could modulate progression to renal failure in patients who already display chronic lesions. Because its role in renal allograft degeneration is not well characterized, whether ACE genotype was associated with the prevalence of chronic allograft nephropathy (CAN) was studied, in a group of protocol biopsies from 180 patients, or with the incidence of CAN in 152 patients with at least two sequential biopsies. As a control group, ACE genotype was also studied in 41 donors and 72 healthy subjects. For analyzing the influence of ACE genotype in graft survival, patients were grouped into six categories (II-normal biopsy, ID-normal, DD-normal, II-CAN, ID-CAN and DD-CAN). Finally, relative renal ACE mRNA levels were measured in 67 cases by real-time PCR using the delta threshold cycle method. ACE-DD genotype was more frequent in patients who received a transplant than in control subjects (43.3% versus 30.1%, P = 0.026), but prevalence (DD = 42.7% versus non-DD = 42.2%) or incidence (DD = 24.6% versus non-DD = 29.9%) of CAN was not different regarding recipient ACE genotype. Furthermore, patients with the ACE-DD genotype and CAN had the poorest graft survival (II-normal = 100%, ID-normal = 91%, DD-normal = 84%, II-CAN = 100%, ID-CAN = 66%, and DD-CAN = 36%; P = 0.034) and higher ACE mRNA levels than non-DD and CAN (DD = −3.36 ± 2.35 versus non-DD = −5.65 ± 1.72-fold in ACE copies; P = 0.012). It is concluded that ACE-DD genotype is not associated with an increased prevalence or incidence of CAN but is actually associated with higher ACE mRNA levels and poorer graft survival in patients who already display CAN.
Low Triiodothyronine
Authors: Carmine Zoccali, Giovanni Tripepi, Sebastiano Cutrupi, Patrizia Pizzini, Francesca Mallamaci
Journal: Journal of the American Society of Nephrology (2005)

Because inflammation influences thyroid function, it was hypothesized that low plasma free triiodothyronine (fT3) in ESRD may be an unsuspected expression of the inflammatory state of these patients. This study investigated (1) the steady-state relationship between fT3 and inflammation markers (IL-6 and C-reactive protein) and markers of endothelial activation (intercellular adhesion molecule-1 [ICAM-1] and vascular cellular adhesion molecule-1 [VCAM-1]) in 200 hemodialysis (HD) patients and (2) the effect of intercurrent acute inflammatory/infectious processes on plasma fT3 in a group of 17 patients with chronic kidney disease (CKD). HD patients displayed lower (P < 0.001) plasma fT3 than healthy subjects (n = 31) and clinically euthyroid patients with chronic diseases and normal renal function (n = 262). When HD patients were subdivided into IL-6 tertiles, fT3 was progressively lower across tertile increments (P < 0.001). Accordingly, regression analysis showed strong and inverse associations (P < or = 0.002) between fT3 and IL-6, C-reactive protein, ICAM-1, and VCAM-1, and, with the exception of the ICAM-fT3 relationship, these associations remained highly significant (P < or = 0.004) in multiple regression analyses adjusting for demographic variables, risk factors, and other potential confounders. In patients who had CKD and were studied during intercurrent inflammatory/infectious processes, fT3 was significantly lower (P = 0.008) at the zenith of inflammation than after its resolution. Low circulating fT3 is frequently observed in inflammatory illnesses, and the same association exists in patients with CKD and in ESRD. This association may entail a causal link because fT3 is acutely and reversibly suppressed in patients with CKD during inflammatory processes triggered by intercurrent infections.
Neutrophils Emigrate from Venules by a Transendothelial Cell Pathway in Response to FMLP
Authors: Dian Feng, Janice A. Nagy, Kathryn Pyne, Harold F. Dvorak, Ann M. Dvorak
Journal: The Journal of Experimental Medicine (1998)

Circulating leukocytes are thought to extravasate from venules through open interendothelial junctions. To test this paradigm, we injected N-formyl-methionyl-leucyl-phenylalanine (FMLP) intradermally in guinea pigs, harvesting tissue at 5–60 min. At FMLP-injected sites, venular endothelium developed increased surface wrinkling and variation in thickness. Marginating neutrophils formed contacts with endothelial cells and with other neutrophils, sometimes forming chains of linked leukocytes. Adherent neutrophils projected cytoplasmic processes into the underlying endothelium, especially at points of endothelial thinning. To determine the pathway by which neutrophils transmigrated endothelium, we prepared 27 sets of serial electron microscopic sections. Eleven of these encompassed in their entirety openings through which individual neutrophils traversed venular endothelium; in 10 of the 11 sets, neutrophils followed an entirely transendothelial cell course unrelated to interendothelial junctions, findings that were confirmed by computer-assisted three-dimensional reconstructions. Having crossed endothelium, neutrophils often paused before crossing the basal lamina and underlying pericytes that they also commonly traversed by a transcellular pathway. Thus, in response to FMLP, neutrophils emigrated from cutaneous venules by a transcellular route through both endothelial cells and pericytes. It remains to be determined whether these results can be extended to other inflammatory cells or stimuli or to other vascular beds.
Inference of Genome Duplications from Age Distributions Revisited
Authors: Kevin Vanneste, Yves Van de Peer, Steven Maere
Journal: Molecular Biology and Evolution (2012)

Whole-genome duplications (WGDs), thought to facilitate evolutionary innovations and adaptations, have been uncovered in many phylogenetic lineages. WGDs are frequently inferred from duplicate age distributions, where they manifest themselves as peaks against a small-scale duplication background. However, the interpretation of duplicate age distributions is complicated by the use of KS, the number of synonymous substitutions per synonymous site, as a proxy for the age of paralogs. Two particular concerns are the stochastic nature of synonymous substitutions leading to increasing uncertainty in KS with increasing age since duplication and KS saturation caused by the inability of evolutionary models to fully correct for the occurrence of multiple substitutions at the same site. KS stochasticity is expected to erode the signal of older WGDs, whereas KS saturation may lead to artificial peaks in the distribution. Here, we investigate the consequences of these effects on KS-based age distributions and WGD inference by simulating the evolution of duplicated sequences according to predefined real age distributions and re-estimating the corresponding KS distributions. We show that, although KS estimates can be used for WGD inference far beyond the commonly accepted KS threshold of 1, KS saturation effects can cause artificial peaks at higher ages. Moreover, KS stochasticity and saturation may lead to confounded peaks encompassing multiple WGD events and/or saturation artifacts. We argue that KS effects need to be properly accounted for when inferring WGDs from age distributions and that the failure to do so could lead to false inferences.
Daily exposure to forty percent oxygen causes a decrease in platelet count
Authors: André F. Meintjes, Roy D. Baynes, Geoff G. Rogers, Barry V. Mendelow
Journal: American Journal of Hematology (1988)

A study was undertaken to evaluate a previous observation made in this laboratory that hyperoxic treadmill training is associated with a decrease in the circulating platelet count (PLT). The subjects studied breathed air containing 40% oxygen for 30 min/day, 5 days/week, for 6 weeks, while at rest in the seated position. Such exposure resulted in a consistent fall in PLT between day 1 and day 5 of each week (P less than .01). In addition, there was a progressive decline in PLT over the 6 weeks of exposure to the hyperoxic air, PLT being inversely correlated with the duration of hyperoxic exposure (rs = -0.886, P less than .02). The total decrease in PLT over the 6 weeks was 56 +/- 46 x 10(9) l(-1) (P less than .025). Not surprisingly, these changes were mirrored in the plateletcrit (Pct). The decrease in PLT did not appear to be secondary to either hemodilution or reduced erythropoietic stimulation. The mechanism of production and the biological significance of these changes remain to be elucidated.
HEPATOERYTHROPOIETIC PORPHYRIA: A NEW UROPORPHYRINOGEN DECARBOXYLASE DEFECT OR HOMOZYGOUS PORPHYRIA CUTANEA TARDA?
Authors: G.H. Elder, S.G. Smith, C. Herrero, J.M. Mascaro, M. Lecha, A.M. Muniesa, D.B. Czarnecki, J. Brenan, V. Poulos, R.E. De Salamanca
Journal: The Lancet (1981)
Lentiviral Vectors Efficiently Transduce Quiescent Mature 3T3-L1 Adipocytes
Authors: Françoise Carlotti, Merlijn Bazuine, Tuija Kekarainen, Jurgen Seppen, Philippe Pognonec, J.Antonie Maassen, Rob C Hoeben
Journal: Molecular Therapy (2004)

Obesity is associated with many serious afflictions such as cardiovascular disease, cancer, and diabetes. One of the main cellular systems used to study the underlying physiological and biological processes is the 3T3-L1 preadipocyte differentiation model. However, studies on 3T3-L1 adipocytes are hampered by the fact that genetic modification of mature adipocytes is notoriously difficult. In this report, we evaluated the use of lentivirus-mediated gene transfer into 3T3-L1 mature adipocytes. We demonstrate that quiescent, fully differentiated 3T3-L1 adipocytes as well as 3T3-L1 preadipocytes can be efficiently transduced with HIV-1-derived lentiviral vectors. Upon transduction using LV-PGK-GFP lentiviral vector at 100 ng p24 per 105 cells, more than 95% of the 3T3-L1 adipocytes in the culture expressed the GFP reporter gene. There were no overt signs of toxicity or cytopathogenicity in the cultures. Furthermore, modification of undifferentiated preadipocytes did not affect their capacity to differentiate. In addition, insulin-induced glucose uptake was not affected by the procedure. In contrast, adenoviral-mediated gene transfer into 3T3-L1 adipocytes is associated with marked cytopathogenicity. From these data, we conclude that lentiviral vectors are the gene-transfer system of choice for genetic modification of mature adipocytes. The availability of an efficient vector system may stimulate the use of adipose tissue as a target for gene therapy in obesity and other disorders.
Nitric oxide synthase activity in the splanchnic vasculature of patients with cirrhosis: relationship with hemodynamic disturbances
Authors: Liliana Albornoz, Alicia Motta, Daniel Alvarez, Alejandra Estevez, Juan Carlos Bandi, Lucas McCormack, Juan Matera, Carlos Bonofiglio, Miguel Ciardullo, Eduardo de Santibañes, Marta Gimeno, Adrián Gadano
Journal: Journal of Hepatology (2001)
Full-term Extra-uterine Pregnancy with Living Child
Authors: G. Gushue-Taylor
Journal: BMJ (1942)

I~~~~~~~~~~~~~~~~~~~~~EIA ORA may well tempt the clinician to hazard conservative measures, with most serious consequences unless immediate relief is at hand. Summary of ConclusionsIt may be of service, therefore, to summarize the features of oedema of the glottis complicating measles and to emphasize a few points which may help to distinguish it from laryngeal diphtheria:Its occurrence may be a feature of certain epidemics, when the incidence is probably under 1 %,o.
Weight changes, medical complications, and performance during an Ironman triathlon
Authors: K A Sharwood, M Collins, J H Goedecke, G Wilson, T D Noakes
Journal: British Journal of Sports Medicine (2004)

Background: Subjects exercising without fluid ingestion in desert heat terminated exercise when the total loss in body weight exceeded 7%. It is not known if athletes competing in cooler conditions with free access to fluid terminate exercise at similar levels of weight loss. Objectives: To determine any associations between percentage weight losses during a 224 km Ironman triathlon, serum sodium concentrations and rectal temperatures after the race, and prevalence of medical diagnoses. Methods: Athletes competing in the 2000 and 2001 South African Ironman triathlon were weighed on the day of registration and again immediately before and immediately after the race. Blood pressure and serum sodium concentrations were measured at registration and immediately after the race. Rectal temperatures were also measured after the race, at which time all athletes were medically examined. Athletes were assigned to one of three groups according to percentage weight loss during the race. Results: Body weight was significantly (p&lt;0.0001) reduced after the race in all three groups. Serum sodium concentrations were significantly (p&lt;0.001) higher in athletes with the greatest percentage weight loss. Rectal temperatures were the same in all groups, with only a weak inverse association between temperature and percentage weight loss. There were no significant differences in diagnostic indices of high weight loss or incidence of medical diagnoses between groups. Conclusions: Large changes in body weight during a triathlon were not associated with a greater prevalence of medical complications or higher rectal temperatures but were associated with higher serum sodium concentrations.
Global, regional, and national estimates of pneumonia burden in HIV-infected children in 2010: a meta-analysis and modelling study
Authors: Evropi Theodoratou, David A McAllister, Craig Reed, Davies O Adeloye, Igor Rudan, Lulu M Muhe, Shabir A Madhi, Harry Campbell, Harish Nair
Journal: The Lancet Infectious Diseases (2014)
Lithocholate metabolism during chenotherapy for gallstone dissolution. 1. Serum levels of sulphated and unsulphated lithocholates.
Authors: R N Allan, J L Thistle, A F Hofmann, J A Carter, P Y Yu
Journal: Gut (1976)

Serum levels of total sulphated and total unsulphated lithocholates were each measured by a specific radioimmunoassay in 66 patients ingesting chenodeoxycholic (chenic) acid for gallstone dissoultion and in 35 gallstone patients ingesting either cholic acid or placebo. No changes occurred in serum lithocholate levels in the control groups. In patients ingesting chenic acid, there was a twofold increase in serum levels of total lithocholate, but the percent sulphation (greater than 75%) remained unchanged during chenotherapy. There was no correlation in the chenic acid treated group between serum lithocholate levels and the proportion of lithocholate in biliary bile acids or changes in serum SGOT. The data suggest that there is effective sulphation of lithocholate in such patients; this may explain the lack of hepatotoxicity observed during ingestion of chenic acid.
α-Myosin Heavy Chain
Authors: Elisa Carniel, Matthew R.G. Taylor, Gianfranco Sinagra, Andrea Di Lenarda, Lisa Ku, Pamela R. Fain, Mark M. Boucek, Jean Cavanaugh, Snjezana Miocic, Dobromir Slavov, Sharon L. Graw, Jennie Feiger, Xiao Zhong Zhu, Dmi Dao, Debra A. Ferguson, Michael R. Bristow, Luisa Mestroni
Journal: Circulation (2005)

Background— Mutations in the β-myosin heavy-chain (βMyHC) gene cause hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy. In failing human hearts, downregulation of αMyHC mRNA or protein has been correlated with systolic dysfunction. We hypothesized that mutations in αMyHC could also lead to pleiotropic cardiac phenotypes, including HCM and DCM. Methods and Results— A cohort of 434 subjects, 374 (134 affected, 214 unaffected, 26 unknown) belonging to 69 DCM families and 60 (29 affected, 30 unaffected, 1 unknown) in 21 HCM families, was screened for αMyHC gene ( MYH6 ) mutations. Three heterozygous MYH6 missense mutations were identified in DCM probands (P830L, A1004S, and E1457K; 4.3% of probands). A Q1065H mutation was detected in 1 of 21 HCM probands and was absent in 2 unaffected offspring. All MYH6 mutations were distributed in highly conserved residues, were predicted to change the structure or chemical bonds of αMyHC, and were absent in at least 300 control chromosomes from an ethnically similar population. The DCM carrier phenotype was characterized by late onset, whereas the HCM phenotype was characterized by progression toward dilation, left ventricular dysfunction, and refractory heart failure. Conclusions— This study suggests that mutations in MYH6 may cause a spectrum of phenotypes ranging from DCM to HCM.
CHEMOTHERAPY OF TRYPANOSOME AND SPIROCHETE INFECTIONS
Authors: Louise Pearce, Wade H. Brown
Journal: The Journal of Experimental Medicine (1919)

N-PhenyIglycineamide-p-arsonic acid is an agent of marked therapeutic action in the treatment of experimental trypanosomiasis of mice, rats, and guinea pigs. It possesses an average curative range of from 0.2 to 0.3 gm. per kilo of body weight of the sodium salt against a 24 hour infection in mice and rats produced by several species of pathogenic trypanosomes. Since the lethal dose for mice is from 2 to 2.25 gm. and for rats 0.75 gm. per kilo of body weight, we have curative ratios of 1:8 and 1:3 respectively. The curative dose for guinea pigs is 0.15 gm. per kilo of body weight, thus giving a curative ratio of 1:10. The trypanocidal activity of this compound is relatively rapid in all three animal species, for the peripheral blood is cleared of organisms within 24 hours after its administration, and in addition, the lower limits of the curative range are comparatively sharply defined. Intraperitoneal, intravenous, and subcutaneous routes of administration for all practical purposes may be considered equally efficacious in Tr. brucei infections of mice both as regards the speed of action of the drug and the average curative range. The administration of the drug in therapeutic amounts in all three animal species is not followed by manifestations of organic or functional injury, but, on the contrary, the genera] physical condition of the treated animals shows an immediate and continued marked improvement. The therapeutic activity in trypanosomiasis of mice, rats, and guinea pigs as evidenced by the relative speed and sharpness of action, together with the curative ratio as expressed in fractions of the minimum lethal dose, and the absence of organic injury or functional disturbance following therapeutic doses are significant and characteristic features of the amide of N-phenylglycine-p-arsonic acid.
Estrogen-Plus-Progestin Use and Mammographic Density in Postmenopausal Women: Women's Health Initiative Randomized Trial
Authors: Anne McTiernan, Christopher F. Martin, Jennifer D. Peck, Aaron K. Aragaki, Rowan T. Chlebowski, Etta D. Pisano, C. Y. Wang, Robert L. Brunner, Karen C. Johnson, JoAnn E. Manson, Cora E. Lewis, Jane M. Kotchen, Barbara S. Hulka
Journal: JNCI Journal of the National Cancer Institute (2005)

Increased mammographic density reduces the sensitivity of screening mammography, is associated with increased breast cancer risk, and may be hormone related. We assessed the effect of estrogen-plus-progestin therapy on mammographic density.In a racially and ethnically diverse ancillary study of the Women's Health Initiative, we examined data from 413 postmenopausal women who had been randomly assigned to receive daily combined conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (i.e., progestin; 2.5 mg) (n = 202) or daily placebo (n = 211). We assessed the effect of estrogen plus progestin on measured mammographic percent density and abnormal findings over a 1-year and 2-year period. All tests of statistical significance were two-sided and were based on F tests or t tests from mixed-effects models.Mean mammographic percent density increased by 6.0% at year 1, compared with baseline, in the estrogen-plus-progestin group but decreased by 0.9% in the placebo group (difference = 6.9%, 95% confidence interval [CI] = 5.3% to 8.5%; P < .001). The mean changes in mammographic density persisted but were attenuated slightly after 2 years, with an absolute increase of 4.9% in the estrogen-plus-progestin group and a decrease of 0.8% in the placebo group (difference = 5.7%, 95% CI = 4.3% to 7.3%; P < .001). These effects were consistent across racial/ethnic groups but were higher among women aged 70-79 years in the estrogen-plus-progestin group (mean increase at year 1 = 11.6%) than in the placebo group (mean decrease at year 1 = 0.1%) (difference of the means = 11.7%, 95% CI = 8.2% to 15.4%; P < .001, comparing across age groups). At year 1, women who were adherent to treatment in the estrogen-plus-progestin group had a mean increase in density of 7.7% (95% CI = 5.9% to 9.5%), and women in the placebo group had a mean decrease in density of 1.1% (95% CI = 0.3% to 1.9%). Use of estrogen plus progestin was associated with an increased risk of having an abnormal mammogram at year 1 (relative risk = 3.9, 95% CI = 1.5 to 10.2; P = .003), compared with placebo, that was not explained by an increase in density.Use of up to 2 years of estrogen plus progestin was associated with increases in mammographic density.