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1.
J Laryngol Otol ; 134(3): 197-204, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32114992

ABSTRACT

BACKGROUND: Cold dissection is the most commonly used tonsillectomy technique, with low post-operative haemorrhage rates. Coblation is an alternative technique that may cause less pain, but could have higher post-operative haemorrhage rates. OBJECTIVE: This study evaluated the peri-operative outcomes in paediatric tonsillectomy patients by comparing coblation and cold dissection techniques. METHODS: A systematic review was conducted of all comparative studies of paediatric coblation and cold dissection tonsillectomy, up to December 2018. Any studies with adults were excluded. Outcomes such as pain, operative time, and intra-operative, primary and secondary haemorrhages were recorded. RESULTS: Seven studies contributed to the summative outcome. Coblation tonsillectomy appeared to result in less pain, less intra-operative blood loss (p < 0.01) and a shorter operative time (p < 0.01). There was no significant difference between the two groups for post-operative haemorrhage (p > 0.05). CONCLUSION: The coblation tonsillectomy technique may offer better peri-operative outcomes when compared to cold dissection, and should therefore be offered in paediatric cases, before cold dissection tonsillectomy.


Subject(s)
Cryotherapy/methods , Dissection/methods , Electrocoagulation/methods , Tonsillectomy/methods , Adolescent , Blood Loss, Surgical , Child , Child, Preschool , Female , Humans , Male , Operative Time , Pain, Postoperative/etiology
2.
Cell Death Differ ; 23(7): 1185-97, 2016 07.
Article in English | MEDLINE | ID: mdl-26868910

ABSTRACT

The pseudokinase, MLKL (mixed-lineage kinase domain-like), is the most terminal obligatory component of the necroptosis cell death pathway known. Phosphorylation of the MLKL pseudokinase domain by the protein kinase, receptor interacting protein kinase-3 (RIPK3), is known to be the key step in MLKL activation. This phosphorylation event is believed to trigger a molecular switch, leading to exposure of the N-terminal four-helix bundle (4HB) domain of MLKL, its oligomerization, membrane translocation and ultimately cell death. To examine how well this process is evolutionarily conserved, we analysed the function of MLKL orthologues. Surprisingly, and unlike their mouse, horse and frog counterparts, human, chicken and stickleback 4HB domains were unable to induce cell death when expressed in murine fibroblasts. Forced dimerization of the human MLKL 4HB domain overcame this defect and triggered cell death in human and mouse cell lines. Furthermore, recombinant proteins from mouse, frog, human and chicken MLKL, all of which contained a 4HB domain, permeabilized liposomes, and were most effective on those designed to mimic plasma membrane composition. These studies demonstrate that the membrane-permeabilization function of the 4HB domain is evolutionarily conserved, but reveal that execution of necroptotic death by it relies on additional factors that are poorly conserved even among closely related species.


Subject(s)
Apoptosis , Evolution, Molecular , Protein Kinases/metabolism , Animals , Apoptosis/drug effects , Cell Line , Cell Membrane Permeability/drug effects , Chickens , HT29 Cells , HeLa Cells , Horses , Humans , Liposomes/metabolism , Mice , Necrosis/genetics , Phosphorylation/drug effects , Protein Domains , Protein Kinases/chemistry , Protein Kinases/genetics , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , Recombinant Proteins/biosynthesis , Recombinant Proteins/chemistry , Recombinant Proteins/pharmacology
3.
Cell Death Dis ; 6: e1809, 2015 Jul 09.
Article in English | MEDLINE | ID: mdl-26158515

ABSTRACT

The BH3-only protein Bim is a potent direct activator of the proapoptotic effector protein Bax, but the structural basis for its activity has remained poorly defined. Here we describe the crystal structure of the BimBH3 peptide bound to BaxΔC26 and structure-based mutagenesis studies. Similar to BidBH3, the BimBH3 peptide binds into the cognate surface groove of Bax using the conserved hydrophobic BH3 residues h1-h4. However, the structure and mutagenesis data show that Bim is less reliant compared with Bid on its 'h0' residues for activating Bax and that a single amino-acid difference between Bim and Bid encodes a fivefold difference in Bax-binding potency. Similar to the structures of BidBH3 and BaxBH3 bound to BaxΔC21, the structure of the BimBH3 complex with BaxΔC displays a cavity surrounded by Bax α1, α2, α5 and α8. Our results are consistent with a model in which binding of an activator BH3 domain to the Bax groove initiates separation of its core (α2-α5) and latch (α6-α8) domains, enabling its subsequent dimerisation and the permeabilisation of the mitochondrial outer membrane.


Subject(s)
Apoptosis Regulatory Proteins/chemistry , Membrane Proteins/chemistry , Peptide Fragments/chemistry , Proto-Oncogene Proteins c-bcl-2/chemistry , Proto-Oncogene Proteins/chemistry , bcl-2-Associated X Protein/chemistry , Amino Acid Sequence , Apoptosis Regulatory Proteins/genetics , BH3 Interacting Domain Death Agonist Protein/chemistry , Bcl-2-Like Protein 11 , Binding Sites , Crystallography, X-Ray , Humans , Membrane Proteins/genetics , Mitochondria/chemistry , Mitochondria/metabolism , Models, Molecular , Mutagenesis , Peptide Fragments/genetics , Protein Binding , Protein Conformation , Protein Structure, Tertiary , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-bcl-2/genetics , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolism
4.
Endoscopy ; 35(12): 985-91, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14648408

ABSTRACT

BACKGROUND AND STUDY AIMS: Even in the era of capsule endoscopy, diseases of the small bowel are sometimes difficult to diagnose, and endoscopic treatment is not possible without surgical laparotomy. The new method of carrying out enteroscopy using a double-balloon technique allows not only diagnostic but also therapeutic endoscopic interventions for lesions in the small bowel. Preliminary experience with this new method is reported here. PATIENTS AND METHODS: Between the end of March 2003 and August 2003, eight patients (four women, four men; mean age 59 +/- 23 years, range 20 - 90) with chronic gastrointestinal bleeding or abdominal pain, or both, underwent enteroscopy using the double-balloon technique. Seven of the patients had been suffering from chronic gastrointestinal bleeding for 56 +/- 49 months (range 3 - 120 months, median 48 months). The lowest hemoglobin levels ranged from 3.6 g/dl to 8.6 g/dl (mean 6.7 +/- 1.7 g/dl), and a mean of 7.6 +/- 5.6 (range 1 - 15) blood units had been transfused. Capsule endoscopy was carried out in six patients, revealing angiodysplasias in three, suspected Crohn's disease in one, fresh blood in the small bowel without a lesion in one, and a focal enanthema in another patient. RESULTS: Enteroscopy with the double-balloon technique was carried out using the oral approach in all patients and additionally with the anal approach in four patients. In two patients with multiple angiodysplasias, it was possible to examine the whole small bowel and to treat the angiodysplasias. All of the capsule endoscopy findings were confirmed; a definite bleeding source was found and treated in two patients with unclear bleeding, and in another patient the real bleeding source was found (not angiodysplasia). The enteroscopy system was easy to handle in all cases. No complications occurred. It was possible to carry out the procedure with the patients under sedoanalgesia. CONCLUSIONS: This new enteroscopy system is easy to handle and seems to be safe. Visualization of the whole small bowel is possible using both the oral and anal approaches. Enteroscopy with the double-balloon technique promises to become a standard method for diagnostic and therapeutic endoscopy of the small bowel without surgical laparotomy.


Subject(s)
Abdominal Pain/etiology , Endoscopy, Gastrointestinal/methods , Gastrointestinal Diseases/diagnosis , Gastrointestinal Hemorrhage/etiology , Adult , Aged , Aged, 80 and over , Angiodysplasia/complications , Angiodysplasia/diagnosis , Crohn Disease/complications , Crohn Disease/diagnosis , Female , Humans , Male , Middle Aged
5.
J Photochem Photobiol B ; 56(1): 12-8, 2000 Jun.
Article in English | MEDLINE | ID: mdl-11073311

ABSTRACT

The effect of the incorporation of the major light-harvesting complex of photosystem II (LHCII) to planar bilayer lipid membranes (BLMs) formed from soybean asolectin and unilamellar small liposomes formed from egg-yolk phosphatidylcholine on ion transport across the lipid bilayer has been studied. The specific conductivity of the BLM rises from 5.2 +/- 0.8 x 10(-9) up to 510 x 10(-9) O(-1) cm(-2) upon the incorporation of LHCII. The conductivity of the membrane with LHCII depends upon the ionic strength of the bathing solution and is higher by a factor of five when the KCl concentration increases from 0.02 to 0.22 M. Such a strong effect has not been observed in the same system without LHCII. The liposome model is also applied to analyse the effect of LHCII on the bilayer permeability to protons. Unilamellar liposomes with a diameter less than 50 nm have been prepared, containing (trapped inside) Neutral Red, a pigment sensitive to proton concentration. A gradient of protons on the membrane is generated by the acidification of the liposome suspension and spectral changes of Neutral Red are recorded in time, reflecting the penetration of protons into the internal space of liposomes. Two components of proton permeation across liposome membranes are observed: a fast one (proceeding within seconds) and a slow one (operating on the time scale of minutes). The rate of both components of proton transport across LHCII-containing membranes is higher than for liposomes alone. The enhancement effect of LHCII on the ion transport across the lipid membrane is discussed in terms of aggregation of the pigment-protein complexes. The possible physiological importance of such an effect in controlling ion permeability across the thylakoid membrane is discussed.


Subject(s)
Lipid Bilayers/chemistry , Liposomes/chemistry , Photosynthetic Reaction Center Complex Proteins/metabolism , Electric Conductivity , Electrochemistry , Kinetics , Lipid Bilayers/metabolism , Liposomes/metabolism , Phosphatidylcholines , Phospholipids , Photosynthetic Reaction Center Complex Proteins/chemistry , Photosystem II Protein Complex , Potassium Chloride , Secale/metabolism , Glycine max
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