Inhibitory monoclonal antibody against a (myristylated) small-molecular-weight antigen from Plasmodium falciparum associated with the parasitophorous vacuole membrane.

A small-molecular-weight antigen that occurs in asexual blood stages in synchronized cultures of Plasmodium falciparum was detected by a monoclonal antibody which inhibits parasite growth in vitro. This antigen, QF116, showed a molecular weight of 15,000 in parasite strain FCR-3K+ from The Gambia and 19,000 in strain FCQ-27 from Papua New Guinea. The protein did not show significant glycosylation by galactose or glucosamine labeling but was found to be acylated by myristic acid. By using immunogold labeling and electron microscopy, the location of the antigen could be attributed to the parasitophorous vacuole membrane and to inclusions and vesicles residing within the cytoplasm of the erythrocyte host cell.     

DR.lyp/lyp bone marrow maintains lymphopenia and promotes diabetes in lyp/lyp but not in +/+ recipient DR.lyp BB rats

Lymphopenia is due to a frameshift mutation in Gimap5 on rat chromosome 4 and is linked to type 1 diabetes in the diabetes prone (DP) BB rat. The hypothesis that bone marrow derived cells confer the lymphopenia phenotype was tested by reciprocal bone marrow transplantation in 40-day-old lethally irradiated diabetes resistant (DR) congenic DR.lyp/lyp (lymphopenia and diabetes) and DR.+/+ (no lymphopenia and no diabetes) rats. In two independent series of transplants, all DR.lyp/lyp rats (n=5 and 4) receiving DR.lyp/lyp bone marrow retained lymphopenia and developed insulitis (5/5 and 4/4) as well as diabetes in some (2/5 and 3/4). Both DR.+/+ and DR.lyp/lyp rats receiving DR.+/+ bone marrow cells as well as DR.+/+ rats receiving DR.lyp/lyp bone marrow cells showed no lymphopenia or diabetes. In accordance with earlier studies in non-congenic BB rats, the DR.+/+ rats receiving DR.lyp/lyp bone marrow cells recapitulated an intermediary phenotype rather than the +/+ or lyp/lyp phenotypes. Our data demonstrate that BBDP rat lymphopenia and diabetes are transferred by bone marrow transplantation to syngeneic DR.lyp/lyp but not DR.+/+ recipients. The intermediary recapitulation of DR.lyp/lyp T cells in recipient DR.+/-/+/- rats suggests that radiation resistant +/-/+/- T cells, the Gimap5 mutation in bone marrow cells, or both may not support the development of lymphopenia.     

Elevated Levels of Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinase 1 during the Acute Phase of Kawasaki Disease

Kawasaki disease (KD) is an acute, self-limiting, multisystem vasculitis of unknown etiology affecting infants and young children. Unless treated promptly with high-dose intravenous gamma globulin and aspirin, patients frequently develop coronary aneurysms. Previously, matrix metalloproteinase 9 (MMP-9), which is secreted complexed to tissue inhibitor of metalloproteinase 1 (TIMP-1), has been implicated in abdominal aortic aneurysm formation. Since the clinical and pathological features of KD include inflammation and weakening of blood vessels, we analyzed acute- and convalescent-phase paired plasma or serum samples from 31 KD patients, 7 patients who did not completely meet the criteria for KD, and 26 non-KD controls (9 febrile and 17 afebrile patients) for pro-MMP-9 (92 kDa) enzyme activity by gelatin zymography and for active MMP-9 (83 kDa), pro-MMP-9, and TIMP-1 protein levels by enzyme-linked immunosorbent assay. Statistical analysis was performed by using Student t tests, linear regression, and the Wilcoxon rank-sum test. Markedly elevated pro-MMP-9 enzymatic activity, pro-MMP-9 protein levels, and TIMP-1 protein levels were found during the acute phase of illness in patients with clinically established KD and in patients who were suspected of having KD but did not meet all of the criteria. There was no significant difference in active MMP-9 levels. Furthermore, pro-MMP-9 and TIMP-1 protein levels were significantly elevated among KD patients, compared to those of febrile and afebrile non-KD controls. The significantly elevated pro-MMP-9 enzyme and protein levels during the acute phase of KD may reflect vascular remodeling or an inflammatory response to a microbial agent, suggesting a pathophysiological role for MMP-9 in coronary aneurysm formation.     

Does the amount of exercising muscle alter the aerobic demand of dynamic exercise?

The primary purpose of this study was to determine if the aerobic demand for production of specified power outputs is altered by distribution of work between the arms and legs compared with when all the work is performed by the legs. Because of the important exercise training implications, a secondary purpose of this study was to determine if the exercising muscle mass affects the cardiorespiratory demands at specified rating of perceived exertion (RPE) levels and blood lactate concentrations. Nine healthy adults completed leg cycling and combined arm and leg exercise on an Airdyne using a discontinuous protocol. Repeated measures ANOVA revealed that oxygen uptake for the combined arm and leg exercise averaged 0.04 l·min⁻¹ greater (p<0.05) than for leg cycling at the same external power outputs. However, RPE levels at specified power outputs were lower (p<0.05) with combined arm and leg exercise than leg cycling. At specified RPE levels and blood lactate concentrations, oxygen uptake and heart rate values were higher (p<0.05) for combined arm and leg exercise than leg cycling. From these findings we conclude that: (1) the addition of arm exercise to leg cycling results in a reduction in RPE, but a minimal increase in oxygen consumption to perform a given power output, and (2) if training intensity is established by RPE or blood lactate concentration, use of a muscle mass larger than that used in leg cycling should allow a greater cardiorespiratory training effect.     

Respiratory syncytial virus associated illness in high-risk children and national characterisation of the circulating virus genotype in South Africa.

BACKGROUND: There is limited information about respiratory syncytial virus (RSV) in high-risk children from developing countries or on the genotype characterisation of the circulating virus. OBJECTIVE: To define the proportion of children with RSV associated lower respiratory tract infections (LRTI) that had risk factors for severe disease and to genotype the circulating RSV strains across the country. STUDY DESIGN: A prospective study was performed in four distinct regions. During April 2000-December 2000 (period 1), all children, with LRTI or without underlying high risk factors for severe RSV disease were enrolled. During January to September 2001 (period 2), only children with LRTI with underlying high risk factors were enrolled. Nasopharyngeal aspirates were evaluated for RSV infection using an ELISA test. RSV isolates were also subtyped and genotyped. RESULTS: Fifty three (24%) of 220 children enrolled during period 1 had risk factors for severe RSV disease; in addition to which a further 38 high-risk children were enrolled during 2001. RSV was isolated from 16 (30%) of 53 and 37 (22%) of 167 high-risk and non-high risk children, respectively, P=0.31. High-risk children were more likely to require intensive unit care (25 vs. 2.7%, P=0.02) and were also more likely to be hospitalised for a longer duration (median 7 vs. 5 days, P=0.06) than non high-risk infants. Overall (periods 1 and 2), RSV was isolated from 34 (37.4%) of the 91 high-risk infants enrolled. Among high-risk children, those from whom RSV was isolated were more likely to require hospitalisation (73.5 vs. 54.4%, P=0.07) and admission to an intensive care unit (14.7 vs. 1.8%, P=0.03) than those from whom RSV was not isolated. Of 40 isolates subtyped during period one, 92.5% were subtype A. Further, 27 (83.3%) of 30 subtype A isolates genotyped during period 1 clustered with GA2. CONCLUSION: RSV is an important cause of LRTI among high-risk infants in a developing country such as South Africa. For the season in question, the genotype that was dominant in Johannesburg was isolated throughout the country, suggesting that successful genotypes may have the ability to spread nationwide.     

A scoping Review of tools used to assess patient Complexity in rheumatic disease

ObjectivePatients with rheumatic diseases often have multiple comorbidities which may impact well‐being leading to high psychosocial complexity. This scoping review was undertaken to identify complexity measures/tools used in rheumatology that could help in planning and coordinating care.MethodsMEDLINE, EMBASE and CINAHL were searched from database inception to 14 December 2019 using keywords and Medical Subject Headings for “care coordination”, “complexity” and selected rheumatic diseases and known complexity measures/tools. Articles describing the development or use of complexity measures/tools in patients with adult rheumatologic diagnoses were included regardless of study design. Included articles were evaluated for risk of bias where applicable.ResultsThe search yielded 407 articles, 37 underwent full‐text review and 2 were identified during a hand search with 9 included articles. Only 2 complexity tools used in populations of adult patients with rheumatic disease were identified: the SLENQ and the INTERMED. The SLENQ is a 97‐item patient needs questionnaire developed for patients with systemic lupus (n = 1 study describing tool development) and applied in 5 cross‐sectional studies. Three studies (a practice article, trial and a cross‐sectional study) applied the INTERMED, a clinical interview to ascertain complexity and support coordinated care, in patients with rheumatologic diagnoses.ConclusionsThere is limited information on the use of patient complexity measures/tools in rheumatology. Such tools could be applied to coordinate multidisciplinary care and improve patient experience and outcomes.Patient contributionThis scoping review will be presented to patient research partners involved in co‐designing a future study on patient complexity in rheumatic disease.     

Associations of Sleep With Sedentary Behavior and Physical Activity Patterns Across Pregnancy Trimesters

IntroductionSleep, sedentary behavior, and moderate-to-vigorous physical activity (MVPA) are altered in pregnancy and may affect pregnancy health; however, how these behaviors are associated with each other is unclear.MethodsPregnant women (N = 120) completed the Pittsburgh Sleep Quality Index and wore an activPAL3 micro and ActiGraph GT3X for 7 days in each trimester to assess sleep, sedentary behavior, and MVPA, respectively. Latent trajectories described patterns of sleep duration, efficiency, and quality as well as sedentary behavior and MVPA. Multinomial logistic regression examined associations of sleep patterns with sedentary behavior and MVPA patterns and, in exploratory analyses, with adverse pregnancy outcomes.ResultsTrajectories were identified for sleep duration (consistently short, 20.7% of sample; consistently adequate, 79.3%), efficiency (consistently low, 17.5%; consistently high, 82.5%), and quality (consistently poor, 15.1%; worsening, 23.5%; and consistently good, 61.5%). Compared with those in more optimal sleep groups, women in the short duration, low efficiency, and worsening quality groups had lower odds of being in the moderate and/or high sedentary behavior group (odds ratio range, 0.21–0.31; 95% confidence interval range, 0.09–0.65). Women in the worsening quality group had greater odds of being in the low MVPA group (odds ratio, 2.51; 95% confidence interval, 1.18–5.38). Trends were observed with women in less optimal sleep groups having greater odds of adverse pregnancy outcomes and lower odds of excessive gestational weight gain.ConclusionsLess optimal sleep patterns in pregnancy are associated with less sedentary behavior and MVPA; additional research is needed to confirm associations between sleep and pregnancy outcomes.     

Agreement between proxy- and self-report scores on PROMIS health-related quality of life domains in pediatric burn survivors: a National Institute on Disability,Independent Living,and Rehabilitation Research Burn Model System Study

Quality of Life Research - To examine agreement between pediatric burn survivor self- and caregiver proxy-report on multiple PROMIS domains and examine factors associated with differences between...     

Diminished expression of the α5β1 integrin (fibronectin receptor) by invasive clones of a human follicular thyroid cancer cell line

Altered adhesion plaques have been observed in transformed cell lines and are associated with enhanced metastatic potential. The prototypical adhesion plaque is formed by 51 fibronectin receptors (FnRs) interacting with the cellular actin network. We have found differences in the actin networks of noninvasive (FTC-133) and invasive (FTC-236, FTC-238) clones of a human follicular thyroid cancer cell line. Furthermore, thyroid-stimulating hormone (TSH) induces stress fibers in FTC-133. In order to investigate differences in adhesion plaques, expression of fibronectin (FN) and its receptor by these cells was analyzed. For these studies FTC-133, FTC-236, and FTC-238 were cultured in serum-depleted DME-H21 medium for 24 hours before the addition of TSH 30 mU/ml. No quantitative differences were noted in FN expression on Western blot in either the conditioned medium or cellular extracts. Western blots and immunohistochemical studies indicated that TSH induced secretion of FN only in FTC-133. Flow cytometry with an 5 antibody demonstrated a 52% and 45% reduction (p<0.01) in expression of FnR by FTC-236 and FTC-238, respectively, compared to FTC-133; this finding was supported by immunohistochemistry results. TSH treatment did not alter FnR expression. From these studies, we conclude that invasive clones of FTC decrease their expression of FnRs without changing their expression of FN. Furthermore, TSH treatment may promote FN secretion by FTC-133, although it does not seem to affect FnR or absolute FN expression. The diminished expression of FnR adhesion plaques may enhance metastatic potential in some follicular thyroid cancers.

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Resumen Se han observado placas adhesivas alteradas en líneas celulares transformadas en asociación con un potencial metastásico incrementado. La prototípica placa adhesiva se forma por la interacción de receptores 5-1 con la trama celular de actina. Hemos encontrado diferencias en las tramas de actina en clones no invasivos (FTC-133) e invasivos (FTC-236, FTC-238) de una línea celular de cáncer folicular de tiroides.Además, la TSH induce líneas de estrés en FTC-133. Con el objeto de investigar las diferencias en las placas adhesivas, se hizo el análisis de la expresión de fibronectina (FN) y sus receptores en tales células.Para estos estudios se hizo el cultivo de FTC-133, FTC-236 y FTC-238, en sueros depletados de DME-H21 por 24 horas anteriores a la adición de 30 mU/ml TSH por 24 horas. No se observaron diferencias cuantitativas en la expresion de FN o en el Western blot ni en los medios condicionados ni en los extractos celulares. Los Western blots y los estudios inmunohistoquímicos indicaron que la TSH induce la secreción de FN sólo en FTC-133. La citometría de flujo con un anticuerpo 5 demostró una reducción de 52% y 45% (p<0.01) en la expresión de FnR por FTC-236 y FT-238, respectivamente, en comparación con FTC-133; este hallazgo fue verificado por inmuno-histoquímica. El tratamiento con TSH no alteró la expresón FnR. Con base en estos estudios, es nuestra conclusión que los clones invasivos de FTC disminuyen la expresión de FnR sin cambiar su expresión de FN. Además, el tratamiento con TSH puede promover la secreciòn de FN por FTC-133, aunque no parece afectar la expresión de FnR o la expresión absoluta de FN. Esta expresión disminuída de las placas adhesivas FnR puede incrementar el potencial metastásico en algunos cánceres foliculares de tiroides.

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Résumé On a observé des altérations des plaques d'adhésion dans certaines lignées cellulaires transformées, et celles-ci semblent être associées à un potentiel métastatique augmenté. La plaque d'adhésion prototypique est formée par des récepteurs 51 de fibronectine (FnR) qui agissent sur le réseau cellulaire d'actine. Nous avons trouvé une différence entre les réseaux d'actine des clones noninvasifs (FTC-133) et invasifs (FTC-236, FTC-238) des lignées cellulaires dans le cancer folliculaire de la thyroïde chez l'homme. La TSH induit des fibres de stress dans le FTC-133. Afin d'évaluer les différences dans les plaques d'adhésion, l'expression de la fibronectine (FN) et de son récepteur ont été analysées. Pour ces études, les clones FTC-133, FTC-236 et FTC-238 ont été mis en culture dans le milieu DME-H21 dépourvu en sérum pendant 24 heures avant l'addition de 30 mU/ml de TSH/24 heures. II n'y avait aucune différence quantitative dans l'expression FN sur Western blot que ce soit sur le milieu ainsi conditionné ou sur les extraits cellulaires. Les Western blots et les études immunohistochimiques ont indiqué que la TSH n'induisait la sécrétion de FN que dans la lignée FTC-133. La cytométrie de flux avec l'anticorps 5 a démontré une réduction respectivement de 52% et de 45% (p<0.01) dans l'expression de FnR par les clones FTC-236 et FTC-238, comparé au FTC-133. Cette donnée a été confirmée par l'immunohistochimie. A partir de ces études, nous concluons que les clones d'invasion de FTC diminuent leur expression en FnR sans changer leur expression de FN. De plus, un traitement par la TSH peut induire la sécrétion de FN par le clone FTC-133 alors qu'il ne semble pas influencer le FnR ou l'expression FN. L'expression diminuée des plaques d'adhésion FnR semble potentialiser les métastases dans certains cancers de la thyroïde.