108 research outputs found
Alteration of the pulmonary surfactant system in full-term infants with hereditary ABCA3 deficiency
No full textRATIONALE: ABCA3 mutations are known to cause fatal surfactant deficiency. OBJECTIVE: We studied ABCA3 protein expression in full-term newborns with unexplained respiratory distress syndrome (URDS) as well as the relevance of ABCA3 mutations for surfactant homeostasis. METHODS: Lung tissue of infants with URDS was analyzed for the expression of ABCA3 in type II pneumocytes. Coding exons of the ABCA3 gene were sequenced. Surfactant protein expression was studied by immunohistochemistry, immunoelectron microscopy, and Western blotting. RESULTS: ABCA3 protein expression was found to be greatly reduced or absent in 10 of 14 infants with URDS. Direct sequencing revealed distinct ABCA3 mutations clustering within vulnerable domains of the ABCA3 protein. A strong expression of precursors of surfactant protein B (pro-SP-B) but only low levels and aggregates of mature surfactant protein B (SP-B) within electron-dense bodies in type II pneumocytes were found. Within the matrix of electron-dense bodies, we detected precursors of SP-C (pro-SP-C) and cathepsin D. SP-A was localized in small intracellular vesicles, but not in electron-dense bodies. SP-A and pro-SP-B were shown to accumulate in the intraalveolar space, whereas mature SP-B and SP-C were reduced or absent, respectively. CONCLUSION: Our data provide evidence that ABCA3 mutations are associated not only with a deficiency of ABCA3 but also with an abnormal processing and routing of SP-B and SP-C, leading to severe alterations of surfactant homeostasis and respiratory distress syndrome. To identify infants with hereditary ABCA3 deficiency, we suggest a combined diagnostic approach including immunohistochemical, ultrastructural, and mutation analysis
Additional file 2: Figure S1. of Categorizing diffuse parenchymal lung disease in children
No full textRoutine work-flow used in the Kids lung register (KLR) to obtain a final working diagnosis and to categorize and subcategorize cases with suspected DPLD (black and red). The work-flow used for re-rating is depicted in red. *reference pathologist was Frank Brasch, **genetical diagnosis was made by Peter Lohse and ***lavage report on surfactant protein analysis, as well as the establishment of the final working diagnosis during routine KLR workflow were done by Matthias Griese. (PDF 176Â kb
Case Report: A rare case of bilateral middle ear tophaceous gout
No full textCamurdan A, Riemann CJ, Brasch F, Todt I. Case Report: A rare case of bilateral middle ear tophaceous gout. Frontiers in Surgery. 2024;11:5 Seiten.
**Introduction**
Hypacusia can be caused by various etiologies; however, hearing loss attributed to gouty tophi remains a rare occurrence. This case report presents, for the first time, a bilateral gouty tophi causing hearing impairment.
**Case presentation**
This report describes a case study involving an 83-year-old Caucasian female patient who presented symptoms of hypacusia, pruritus, and a sensation of pressure in her right ear. A computed tomography scan revealed the presence of non-homogeneous calcified structures in both ears. Following a comprehensive assessment that included pure-tone audiometry and a thorough evaluation of the patient's clinical complaints, a tympanoplasty procedure was initially performed on the right ear. Pathological analysis revealed the presence of gouty tophi. After surgical removal of the tophus, a notable improvement in the patient's hearing threshold was observed. Four months later, a similar surgical intervention was performed on the contralateral ear, achieving a similar positive outcome. The substantial postoperative decrease of bone conduction indicates an inner ear affection by the gout tophi.
**Conclusion**
Gout tophus in both ears is a very rare but possible cause of hypacusia, even in the absence of a pre-existing diagnosis of systemic gout disease. We report a case of gout tophi in both ears as a rare cause of hearing loss.
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Feathers and lime
No full textThe author, Ken Cockburn, is an internationally recognised poet and writer. His first collection of poems was shortlisted for a Saltire award; He established and ran, along with Alec Finlay, pocketbooks which was an award winning series of books of poetry and visual art. This book is a collection of translated poems and features work by Thomas Brasch, Rudolf Bussmann, Christine Marendon, Arne Rautenberg and Tina Stroheker. Other than Brasch, this is the first time work by these poets has appeared in English in book form.</p
Genanalysis in Patients with acute intermittent Porphria
No full textTitel und Inhaltsverzeichnis
1. EINLEITUNG 1
1.1
1.2
1.3 Rückblick
Akute Intermittierende Porphyrie - Übersicht
Fragestellungen 1
3
26
2. PATIENTEN UND METHODEN 27
2.1
2.2 Patienten
Methoden 27
30
3. ERGEBNISSE 41
3.1
3.2
3.3
3.4
3.5 Resultate Methode 1 (DGGE)
Resultate Methode 2 (SEA)
Resultate Methode 3 (EIS)
Familienanalyse
Zusammenfassung der Resultate 41
43
45
46
48
4. DISKUSSION 51
4.1
4.2
4.3
4.4
4.5
4.6 Bedeutung dieser Arbeit
Abwägungen zur AIP-Diagnostik
Abwägung zu den genanalytischen Ansätzen dieser Studie
Erläuterungen zu den Resultaten
Genotyp-Phänotyp-Beziehungen
Liste aller PBGD-Mutationen (Stand 12/2004) (eigene Liste) 51
51
54
55
57
59
5. ZUSAMMENFASSUNG 65
6. REFERENZEN 67
7. LINKS 80
8. VERÖFFENTLICHUNGEN 81Die Akute Intermittierende Porphyrie (AIP) ist eine extrem seltene Erkrankung.
In Deutschland existiert kein zentrales Register für AIP-Patienten und viele
Ärzte sind ungeübt, diese Erkrankung zu erkennen. Nur durch eine
deutschlandweite Publikation über die Akute Intermittierende Porphyrie
(Petrides, 1997) war es möglich, Proben von 20 AIP-Patienten
zusammenzustellen; damit ist diese Arbeit die bisher größte genanalytische
Untersuchung von AIP-Patienten in Deutschland. Bis zu dieser Studie waren die
Genanalysen von drei AIP-Patienten aus Deutschland veröffentlicht worden
(Petrides, 1998; Puy et al., 1998). Bezogen auf alle relevanten
Veröffentlichungen bisher, wurden in dieser Arbeit 20 von 28 (71%) aller in
Deutschland nachgewiesenen PBGD Mutationen identifiziert (Petrides, 1998; Puy
et al., 1998; Gross et al., 1999; Von Brasch et al., 2004). Dabei wurden 11
von 17 Neuentdeckungen von Mutationen des PBGD-Gens in Deutschland gemacht.
Das sind ca. 5% aller seit 1989 veröffentlichten PBGD Mutationen weltweit. Die
Ergebnisse der Genanalyse zeigen außerdem, daß es in Deutschland keine
prädominierenden AIP-Mutationen gibt, wie z.B. in Schweden, sondern daß es
viele verschiedene, private Mutationen gibt. Die Genanalysen wurden mit drei
verschiedenen Ansätzen durchgeführt: Erstens, die Denaturierende-
Gradientengel-Elektrophorese-Analyse mit anschliessender Sequenzierung,
zweitens, die Sequenzielle Exon-Analyse (SEA), d.h. Sequenzierung einzelner
Exons nach Auswahl durch statistische Kriterien und drittens, die Exon-Intron-
Sequenzierung (EIS), d.h. Sequenzierung großer, zusammenhängender Stücke des
PBGD-Gens. Mit allen drei Methoden konnten Mutationen identifiziert werden.
Die dritte Methode, die Exon-Intron-Sequenzierung (EIS) ermöglichte es aber,
eine neue Mutation zu entdecken die in einem Intronbereich lag, der mit den
bisher in der medizinischen Literatur publizierten, genanalytischen Methoden
nicht untersucht worden war. Von den, in dieser Arbeit beschriebenen 11 neu
entdeckten Mutationen, 7 in Intronsequenzen identifiziert worden; 6 davon mit
der EIS-Methode. Damit zeichnet sich diese Methode gegenüber den
vorangegangenen durch ihre hohe Sensitivität aus.Acute intermittent porphyria (AIP) is a rare autosomal dominant disorder with
low penetrance. It is caused by mutations in the porphobilinogen deaminase
(PBG-D) gene that lead to a deficiency of the third enzyme of the heme
biosynthetic pathway. Upon up regulation of heme biosynthesis, an excess of
heme precursors causes clinical symptoms. Because the disease is rare and
symptoms vary, diagnosis is often delayed. In this study three approaches for
PBG-D gene-analysis were used: first, Denaturing Gradient Gel Electrophoresis
(DGGE) followed by sequencing, secondly, selected stepwise sequencing and
thirdly, sequencing extensive parts of the gene. DNA of 20 unrelated
individuals has been screened and 20 different mutations were revealed. Of
these, eleven had not been reported previously. The novel mutations were
identified in intron 1 (33 + 2 T-C), exon 5 (181 G-C), intron 6 (267 61 del 8
bp), intron 7 (345 1 G-C), intron 9 (498 + 15 G-T and 499 13 D-14 bp indel
TGA), intron 13 (825 + 1 G-C and 825 + 2 T-C), exon 15 (962 G-A, 1067 del A
and 1067 1068 ins 5bp). The other nine mutations detected, affected intron 14,
exons 6-10 and exon 12. Avoidance of triggers may prevent clinical
manifestation of the disease. Hence, early identification of AIP gene carriers
is of great importance. To obtain this goal, a diagnostic algorithm is being
suggested and genetic screening was performed in five families, revealing 10
additional AIP gene carriers. A correlation between the genotype and the
phenotype of the disease has not become apparent
Research in medical education - chances and challenges : international conference, 20th - 22nd May 2009, Heidelberg ; congress abstracts
No full textNonspecific Interstitial Pneumonia, Alveolar Proteinosis, and Abnormal Proprotein Trafficking Resulting from a Spontaneous Mutation in the Surfactant Protein C Gene
No full textHuman surfactant protein C (hSP-C1-197) is synthesized as a 197 amino acid proprotein and cleaved to a mature 3.7 kD form. Although interstitial lung disease in patients with mutations of the hSP-C gene is becoming increasingly recognized, the mechanisms linking molecular events with clinical pathogenesis are not fully defined. We describe a full-term infant with respiratory insufficiency associated with a spontaneous heterozygous mutation resulting in a substitution of lysine for glutamic acid at position 66 (= E66K) of the proximal hSP-C COOH flanking propeptide. Lung histology and biochemical studies of the index patient (hSp-C-E66K) revealed nonspecific interstitial pneumonia, increased alveolar total phospholipid lacking phosphatidylglycerol, and increased surfactant protein A. Localization of proSP-C from lung sections prepared from this patient using immunofluorescence and immunogold electron microscopy revealed abnormal proSP-C staining in endosomal-like vesicles of type II cells distinct from SP-B. To evaluate the effect of the E66K substitution on intracellular trafficking of proSP-C, fusion proteins consisting of enhanced green fluorescent protein (EGFP) and hSP-C1-197 (wild type) or mutant hSp-C-E66K were generated and transfected into A549 cells. EGFP/hSP-C1-197 was expressed within CD-63-positive, EEA-1-negative vesicles, whereas EGFP/hSP-C-E66K localized to EEA-1 positive vesicles. The E66K Substitution is representative of a new class of SP-C mutation associated with interstitial lung disease that is diverted from the normal biosynthetic pathway. We propose that, similar to other storage disorders, lung injury results from induction of a toxic gain of function induced by the mutant product that is subject to genetic modifiers and environmental influences.NHLBI NIH HHS [HL 076064, HL-19737, P50-HL56401
Formen und Bedeutung der Weltanschauungsliteratur bei Kurd Lasswitz
No full text1.« Formen und Bedeutung der Weltanschauungsliteratur bei Kurd Lasswitz » in Anna S. Brasch/ Christian Meierhofer (ed.), Weltanschauung und Textproduktion. Beiträge zu einem Verhältnis in der Moderne. Berlin Peter Lang 2020 (Berliner Beiträge zur Wissens- und Wissenschaftsgeschichte, Bd. 18), p. 235-267.International audienceKurd Lasswitz’s fundamental concern was to simultaneously foster the progress of the natural sciences and to protect the legitimacy of religious belief. This contribution will investigate the argumentative, rhetorical, and stylistic means that Lasswitz employs in order to defend his difficult position. In the course of the investigation, the discrepancy between the various texts concerning world-views and his productive activity as a writer will become evident, the latter of which takes up the same themes and topics, yet clearly deviates from them with respect to its tone and goal. The author is constantly concerned with providing a basis for an understanding of the world that depends on natural science and is yet to maintain the rights of ethics and aesthetics for the sake of “progress of the process of culture”
Authorial Self-Consciousness in the Fiction of John Barth
No full textThis thesis deals with .the development of the self-conscious authorial voice in the fiction of John. Barth, especially as this self-consciousness relates to the fictional form in which it is found-realistic, fabular, and metafictional. Each chapter will deal with two of Barth's works, which themselves will also be dealt with chronologically. Chapter I will deal with the authorial self-consciousness in the realist mode, as seen in The Floating Opera and The End of the Road. Chapter II will consider the self-conscious presence of the author-figure in The Sot"':"Weed Factor and Giles Goat-Boy, both of which are attempts to create whole fictional universes, and which indicate in their form the exhaustion of the realist mode for Barth' s purposes. Chapter III will deal with Bartht's metafictional shorter works in Lost in the Funhouse and Chimera, works which take the continual exhaustion of fictional forms as their donnee or subject matter, and which emblematically as well as thematically attempt to describe the dynamics of this exhaustion. Attention will be paid to the last novella "Bellerophoniad," since it stands as Barth's ultimate gesture of exhaustion, culminating and devouring as it does all of Barth's previous fictional corpus. In addition, there is an Appendix containing a glossary of equivalent terms for those found in the allegorical Giles Goat-Boy. This is intended as a short reader's guide, and is by no means exhaustive.Master of Arts (MA
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