5,150 research outputs found
Effectiveness of growth hormone therapy in children with Noonan syndrome
No full textPURPOSE: Recombinant human growth hormone (rhGH) has been used to improve growth in children with Noonan syndrome (NS). This study aimed to investigate the efficacy of rhGH therapy in Korean children with NS. METHODS: Seventeen prepubertal children (10 boys, 7 girls) with NS who received rhGH therapy for at least 3 years between 2008 and 2017 were included. To compare the response, age- and sex-matched children with GH deficiency (GHD; n=31) were included. Height and growth velocity before and during treatment were analyzed. RESULTS: The mean age of NS patients was 6.34+/-2.32 years. After treatment, the height standard deviation score (SDS) increased from -2.93+/-0.81 to -1.51+/-1.00 in patients with NS and from -2.45+/-0.42 to -1.09+/-0.47 in patients with GHD. There were no significant differences in growth velocity or change in height SDS between patients with NS and GHD. Growth velocity in the first year of treatment was higher in patients with PTPN11 mutations than those without PTPN11 mutations, but the change in height SDS was not significantly different between those 2 groups. CONCLUSION: rhGH therapy can increase linear growth in prepubertal children with NS. The growth response between patients with NS and patients with GHD was not significantly different. Furthermore, we observed that lower doses of growth hormone have a similar effect on height compared to previous studies in patients with NS. Our study indicates that rhGH treatment is useful for growth promotion
Identification of rare missense mutations in NOTCH2 and HERC2 associated with familial central precocious puberty via whole-exome sequencing
No full textOBJECTIVE: Genetic factors play a critical role in pubertal progression; however, mutations associated with central precocious puberty (CPP) have been reported only in four genes: KISS1, KISS1R, DLK1, and MKRN3. This study aimed to identify novel, potentially pathogenic variants in patients with familial CPP via whole-exome sequencing (WES).
METHODS: WES analysis was applied in 28 patients (25 girls and three boys) belonging to 14 families, wherein all siblings were diagnosed with CPP. Data analysis aimed to select only very rare variants (minor allele frequency <1%). Nonsense, splice-site, and frameshift variants were considered the most ideal candidate variants. Additionally, non-synonymous missense variants predicted as being deleterious using in silico analysis tools were further considered.
RESULTS: The analysis of exome sequencing data resulted in the identification of rare mutations in two promising candidate genes (NOTCH2 and HERC2) in a family. Siblings with CPP exhibited two heterozygous missense mutations (p. Leu15Phe in NOTCH2 and p. Arg4081His in HERC2). Moreover, their parents without history of CPP had a missense variant in either NOTCH2 or HERC2.
CONCLUSIONS: We identified new candidate genes with potential roles in pubertal development. Digenic inheritance of the two genetic mutations associated with the Notch signaling pathway may have a synergistic effect resulting in CPP
Isolierung und Charakterisierung von Zellwandkomponenten der gram-positiven Bakterienstämme Lysinibacillus sphaericus JG-A12 und JG-B53 und deren Wechselwirkungen mit ausgewählten relevanten Metallen und Metalloiden
No full textDurch die Untersuchungen der vorliegenden Arbeit ist es erfolgreich gelungen die beiden gram-positiven Mikroorganismen Lysinibacillus sphaericus JG-A12 und Lysinibacillus sphaericus JG-B53 unter geregelten und idealen Kultivierungsbedingungen im Bioreaktor in hinreichenden Biomasseausbeuten zu kultivieren. Aus der Biomasse beider Stämme ist es anschließend gelungen, die primären Zellwandkomponenten bestehend aus Membranlipiden, Peptidoglykan mit sekundären Zellwandpolymeren und S-Layer-Proteinen in reiner Form und in guten Ausbeuten zu extrahieren. Diese Zellwandkomponenten wurden dann unter Verwendung von biochemischer und strukturanalytischer Methoden charakterisiert. Dabei ist es erstmals gelungen, die Membranlipide beider genutzter Mikroorganismen in Bezug auf deren Zusammensetzungen der enthalten hydrophoben Fettsäuren und der hydrophilen phosphathaltigen Kopfgruppen zu charakterisieren.
Durch die vergleichend durchgeführten Metallbindungsversuche im Batch-Verfahren konnten Bindungspräferenzen intakter Zellen von Lysinibacillus sphaericus JG-A12 und Lysinibacillus sphaericus JG-B53 und deren isolierten Zellwandkomponenten mit den Metallen As, Au, Cd, Eu, Pb, Pd, Pt bzw. U untersucht werden. Dabei konnten sowohl in den Untersuchungen intakter Zellen und der primären Zellwandbestandteile deutlich höhere Metallsorptionsraten und Metallentfernungseffizienzen für Lysinibacillus sphaericus JG-B53 festgestellt werden als dies bei Lysinibacillus sphaericus JG-A12 nachzuweisen war. Dies macht diesen Stamm für potentielle technische Anwendungen als metallselektives biosorptives Material weitaus interessanter.
Die Untersuchungen der Einzelkomponenten in Suspension lieferten jedoch nur begrenzt Informationen zur Interaktion der Metalle mit den Schichten wie sie unter natürlichen Bedingungen in der Zelle vorkommen. Daher wurden unter Verwendung der QCM-D erstmals die primären Zellwandkomponenten beider Mikroorganismen (S-Layer und Peptidoglykan) sowie von Referenzlipiden an Grenzflächen erfolgreich im nanoskaligen Bereich abgeschieden und online verfolgt. Dadurch war es möglich vereinfachte Einzelschichtsysteme der gram-positiven bakteriellen Zellwand nachzubilden.
In den Untersuchungen konnten stabile Schichten generiert werden, welche vergleichbar zu dem Schichtsystem vitaler Zellen sind. Zusätzlich konnte bei den Abscheidungen der S-Layer-Proteine SlfB und Slp1 der positive Effekt von Polyelektrolytmodifizierungen auf das Rekristallisationsverhalten, die Schichtstabilität und den Bedeckungsgrad auf der technischen Oberfläche aufgezeigt werden. Zur Untersuchung der Metallinteraktion zellulärer Einzelschichtsysteme wurden in dieser Arbeit exemplarisch nach den erfolgreichen Untersuchungen zur Rekristallisation, die S-Layer-Proteine als erste Interaktionsschicht des Gesamtzellsystems mit der QCM-D untersucht. Diese stabilen und intakten Schichten konnten analog zu den Schichtuntersuchungen der reinen biologischen Komponenten und nach den QCM-D Metallinteraktionsstudien mit den S-Layer Strukturen mittels der Rasterkraftmikroskopie (AFM) untersucht und bildgebend dargestellt werden.
In weiteren spektroskopischen Untersuchungen (TRLFS) der Zellwandkomponenten konnten die lumineszierenden Eigenschaften von Europium ausgenutzt werden, um das Metallbindungsverhalten der einzelnen Komponenten als auch des Gesamtsystems der Zellen beider Mikroorganismen zu bestimmen. Somit konnte Europium als spektroskopische Sonde eingesetzt werden um Rückschlüsse die Biomolekül-Metallwechselwirkungen zu ermöglichen. Dabei konnten vor allem mit den beiden oberflächennahen Zellschichten Lösung teilweise sehr starke Metall-Biomolekül-Wechselwirkungen beobachtet werden
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No full textEdition of 10, 9 TI, BAT, 5 AP, 5 CTP (1 white CD, 1 MI, 1 JG, 2 cream CD), PTP (JG), CPGerman Etching Paperblac
Practical management of NSCLC patients with long-term bevacizumab treatment: a report of four cases
No full textGJM Herder,1 H Codrington,2 CD Colder,3 JG Aerts4,51St Antonius Hospital, Nieuwegein, The Netherlands; 2Haga Hospital, The Hague, The Netherlands; 3St Jansdal Hospital, Harderwijk, The Netherlands; 4Amphia Hospital, Breda; 5Erasmus MC Rotterdam, The NetherlandsIntroduction: Previous research showed that the addition of bevacizumab (a monoclonal antibody against vascular endothelial growth factor [VEGF]) to chemotherapy resulted in a significant efficacy benefit in the treatment of selected patients with advanced nonsquamous non–small cell lung cancer (NSCLC). However, the occurrence and management of adverse events (AEs) during long-term maintenance treatment with bevacizumab is not well known.Methods: This report presents a descriptive analysis, including the management of AEs, of four patients with advanced NSCLC, who received a relatively long period of bevacizumab maintenance treatment.Results: In patient 1, a 72-year-old retired man with stage cT2N2M1b NSCLC, the only AE related to bevacizumab was a grade 1 rhinorrhea. Treatment resulted in a stable disease, with duration of response of 38 months. Patient 2 had NSCLC stage cT4N3M1b and developed a cavitation and infection after the first cycle of chemotherapy and bevacizumab, which caused a temporary decrease of her quality of life. Bevacizumab therapy resulted in a partial response, with duration of response of 15 months. A 52-year-old female (patient 3) with stage T2bN2M1a NSCLC is currently under treatment and has so far received 42 cycles of maintenance bevacizumab, with stabilized response (duration of response of 29 months) and no noteworthy AEs. The last patient is a 74-year-old male farmer with NSCLC T1N0M1, whose response has lasted for more than 3 years, with until now, no AEs.Conclusion: Our retrospective findings of these four patients show the long-term efficacy and safety of bevacizumab treatment in a real-life setting.Keywords: lung cancer, non–small cell lung cancer, maintenance treatment, safety managemen
Newspaper (Shut-in Suite XIV)
No full textEdition of 20, 9TI (JG), BAT, 4 AP (1JG), 2 PP (JG), 1 TP, 2 PTP (1 cream CD, 1 wN), CP (JG)Crisbrook Waterleafblac
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No full textEdition of 20, 9 TI (JG), BAT, 4 CTP (3 JG, 1 CD), 3 PTP* (2 CD), CPMagnani Italia(1) yellow (2) black (Same stone as run 1 printed off-register.
Spectroscopic characterization of gold nanoparticles formed by cells and S-layer protein of Bacillus sphaericus JG-A12
No full textAbstract The strain Bacillus sphaericus JG-A12, isolated from a uranium mining waste pile near the town of Johanngeorgenstadt, is capable of selective and reversible accumulation of U, Cu, Pb, Al, and Cd from uranium waste waters. The cells of this strain are enveloped by a surface layer protein (S-layer). The highly regular structure of this S-layer with many pores of identical size offers good binding sites for different kinds of molecules and provides nucleation sites for the formation of metal nanoclusters or minerals. In this study we demonstrate that B. sphaericus JG-A12 cells and their purified S-layer protein were capable to reduce Au to metallic nanoclusters in the presence of reducing agents such as molecular H 2 . The gold nanoparticles were regularly distributed and sized according to the pores of the protein lattice. The metallic nature of the clusters was confirmed by different techniques such as extended X-ray absorption fine structure (EXAFS) spectroscopy, X-ray absorption near edge (XANES) spectroscopy, UV-vis spectroscopy and X-ray powder diffraction (XRD). The size of the gold nanoparticles was estimated to be almost 1 nm. Our results demonstrate that B. sphaericus JG-A12 can be used to prepare gold nanoparticles tailor-made for industrial applications
Coeliac disease: where are we in 2014?
No full textPresents up-to-date information on coeliac disease, with recommendations on whom to test and how to test them, and how to manage patients once they are diagnosed.
Summary
Background
Coeliac disease (CD) is an autoimmune condition affecting at least 1% of the population, many of whom remain undiagnosed. It is characterised by chronic inflammation of the small-intestinal mucosa and triggered by eating gluten. It is challenging to diagnose because of the many and varied ways in which it may present.
Discussion
Primary care practitioners have a crucial role in improving rates of CD diagnosis, and in the ongoing care of patients with CD. A blood test for coeliac-specific antibodies will identify most patients who need to undergo duodenal biopsy to make the diagnosis. Management encompasses supporting patients with adherence to the gluten-free diet and conducting a CD-focused clinical review every 1–2 years
Invariant tori and Lagrange stability of pendulum-type equations
No full textAbstractIn this paper we prove that the pendulum-type equation x″ + g(t, x) = 0 possesses infinitely many invariant tori whenever g(t, x) has zero mean value on the torus T2, where g(t, x) belongs to C∞(T2). This yields the boundedness for solutions of the considered pendulum-type equation and thus leads to an answer to J. Moser's boundedness problem (1973, Ann. of Math. Stud. 77)
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