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Walk-through injuries: glass door facial injuries.

During 1998, 13 patients were treated in the Tel-Aviv Sourasky Medical Center for complex facial soft-tissue injuries caused by passing through large, clear glass doors. All epidemiological details were gathered and analyzed. Of 1,100 soft-tissue facial injury admissions in 1 year, 13 patients had a substantial soft-tissue facial injury after passing through a glass barrier. Nine were injured during leisure time activity, five in a shopping mall, and four in their residence. Interestingly, the authors found a common pattern of facial injuries in all patients. It consisted of large, irregular, composite skin and soft-tissue flaps as well as large, tom, irregular skin lacerations. The nose was injured predominantly, and the injury was particularly complex. Their recommended management of these injuries is a thorough and careful evaluation of flap viability. Surgical management of avulsed, viable flaps includes margin debridement and repositioning. If the flap is narrow enough, it can be debrided and the margins adapted primarily. If viability of part of the flap is in doubt, that part should be debrided and used as a composite graft. When this graft dies, a full-thickness graft is taken from another facial site. The cosmesis of such a graft is better than using the debrided, thin segment as a skin graft that is too thin. The authors emphasize that there is a need to encourage authorities to reinforce regulations relating to injury prevention from architectural glass. The first is to use special glazing, either tempered glass, laminated glass, or both. The other method of improving safety is by indicating glass using decorations or warning stickers, or by making it partly translucent. Unless these regulations are obeyed, fatal or complex trauma may occur.

Adult↗

Vta1p and Vps46p regulate the membrane association and ATPase activity of Vps4p at the yeast multivesicular body.

Previous two-hybrid analysis of the 17 soluble class E Vps yeast proteins revealed that Vps46p/Did2p interacts with Vta1p and the AAA (ATPase associated with a variety of cellular activities) ATPase Vps4p. Here we report that the binding of Vps46p to Vps4p and Vta1p is direct and not mediated by additional proteins, and the binding of Vps46p to Vps4p is ATP independent. Vps46p regulates the membrane association of Vps4p and is required for the interaction of Vta1p with Vps32p/Snf7p of the ESCRT-III complex. Vta1p is a potent activator of Vps4p, stimulating the ATPase activity by 6- to 8-fold. These results reveal functional roles for the Vps46p and Vta1p proteins in regulating the ESCRT complex assembly/disassembly cycle in protein sorting at the yeast late endosome.

Adenosine Triphosphatases↗

Host-guest chemistry of copper(II)-histidine complexes encaged in zeolite Y.

Structural analysis has been carried out on copper(II)-histidine (Cu(2+)/His) complexes after immobilization in the pore system of the zeolites NaY and de-aluminated NaY (DAY). The aim of this study was to determine the geometrical structure of Cu(2+)/His complexes after encaging, to obtain insight into both the effect of the zeolite matrix on the molecular structure and redox properties of the immobilized complexes. In addition to N(2) physisorption and X-ray fluorescence (XRF) analyses, a combination of UV/Vis/NIR, ESR, X-ray absorption (EXAFS and XANES), IR, and Raman spectroscopy was used to obtain complementary information on both the first coordination shell of the copper ion and the orientation of the coordinating His ligands. It was demonstrated that two complexes (A and B) are formed, of which the absolute and relative abundance depends on the Cu(2+)/His concentration in the ion-exchange solution and on the Si/Al ratio of the zeolite material. In complex A, one His ligand coordinates in a tridentate facial-like manner through N(am), N(im), and O(c), a fourth position being occupied by an oxygen atom from a zeolite Brønsted site. In complex B, two His ligands coordinate as bidentate ligands; one histamine-like (N(am), N(im)) and the other one glycine-like (N(am), O(c)). In particular the geometrical structure of complex A differs from the preferred structure of Cu(2+)/His complexes in aqueous solutions; this fact implies that the zeolite host material actively participates in the coordination and orientation of the guest molecules. The tendency for complex A to undergo reduction in inert atmosphere to Cu(1+) (as revealed by dynamic XANES studies) suggests activation of complex A by the interaction with the zeolite material. EXAFS analysis confirms the formation of a distorted four coordinate geometry of complex A, suggesting that the combination of zeolite and one His ligand force the Cu(2+) complex into an activated, entactic state.

Copper↗

Chiral discrimination in cyclodextrin complexes of amino acid derivatives: beta-cyclodextrin/N-acetyl-L-phenylalanine and N-acetyl-D-phenylalanine complexes.

In a systematic study of molecular recognition of amino acid derivatives in solid-state beta-cyclodextrin (beta-CD) complexes, we have determined crystal structures for complexes of beta-cyclodextrin/N-acetyl-L-phenylalanine at 298 and 20 K and for N-acetyl-D-phenylalanine at 298 K. The crystal structures for the N-acetyl-L-phenylalanine complex present disordered inclusion complexes for which the distribution of guest molecules at room temperature is not resolvable; however, they can be located with considerable confidence at low temperature. In contrast, the complex with N-acetyl-D-phenylalanine is well ordered at room temperature. The latter complex presents an example of a complex in this series in which a water molecule is included deeply in the hydrophobic torus of the extended dimer host. In an effort to understand the mechanisms of molecular recognition giving rise to the dramatic differences in crystallographic order in these crystal structures, we have examined the intermolecular interactions in detail and have examined insertion of the enantiomer of the D-complex into the chiral beta-CD complex crystal lattice.

Amino Acids↗

Proximal vascular pedicle preservation for sartorius muscle flap transposition.

BACKGROUND: A variety of muscle flaps have been described to treat complex groin wounds associated with infected and/or exposed femoral vessels or vascular grafts and persistent lymphatic leaks, and for prophylaxis against wound breakdown following inguinal lymphadenectomy. The sartorius muscle flap has several advantages over other muscle flaps: it is immediately adjacent to the groin, it is easy to prepare, and the harvest causes no functional morbidity. Despite these advantages, the flap's reliability has been questioned because of the segmental blood supply to the muscle and the flap's limited arc of rotation. To improve the reliability of the flap, the authors defined the proximal vascular anatomy of the sartorius muscle in 20 human cadavers and assessed the correlation with 20 clinical cases. They describe a technique for the harvest of the sartorius muscle transposition flap that preserves the most proximal pedicle. METHODS: From July of 2000 to January of 2004, 40 sartorius muscles were dissected in 20 human preserved cadavers. During the same time period, 21 sartorius muscle transposition flap procedures were performed in 19 patients for a variety of complex groin wound complications, including infection (n = 10), lymphadenectomy (n = 4), lymphatic leak (n = 3), exposed femoral vessels (n = 3), and high-risk wound (n = 1). The location of the most proximal vascular pedicle with respect to the anterior superior iliac spine was measured in each cadaveric dissection as well as in each clinical case. Outcomes were assessed in the clinical cases with respect to wound healing. RESULTS: The distance between the anterior superior iliac spine and the proximal vessels in the cadaver specimens was 6.6 +/- 1.3 cm (range, 5.0 to 9.5 cm). The distance between the anterior superior iliac spine and the proximal vessels in the clinical patients was 6.2 +/- 0.6 cm (range, 5.5 to 7.5 cm). Patients were followed for an average period of 30 months (range, 5 to 45 months). There were no incidences of partial or total flap necrosis. All wounds healed to completion. CONCLUSIONS: The proximal pedicle of the sartorius muscle is consistently located at 6.5 cm from the anterior superior iliac spine. Preservation of the proximal pedicle during dissection ensures the viability of the sartorius muscle transposition flap for the treatment of complex groin wounds.

Adult↗

Complement-dependent anaphylactic reactions.

The concept of elicitation of reactions of anaphylactic type by non-tissue-fixing antibody, through activation of complement and release of anaphylatoxins by antigen-antibody complexes in vivo, is not clearly defined by published evidence. Experimental data are presented to demonstrate that guinea pig immunoglobulin G2 (noncytotropic) complexed with antigen in vitro elicits dermal reactions in guinea pigs, and that pretreatment of animals with complement-inactivating cobra venom factor diminishes such reactions. The various pathways through which immediate hypersensitive reactions may occur are discussed.

Anaphylaxis↗

Do you see what I see? Interpretations of intentional movement in schizophrenia.

OBJECTIVE: Current literature exploring theory of mind (ToM) abilities in patients with schizophrenia has failed to take into account the dynamic nature of complex social interactions. The aim of this study was to explore symptom specific impairments in theory of mind using a novel, dynamic task. METHODS: Subjects viewed short animations displaying three types of movement; random, goal directed, and socially complex (theory of mind). Verbal descriptions of the animations were obtained from 61 patients with schizophrenia (divided into symptom sub-groups) and 22 healthy comparison subjects and were scored for accuracy, type of response and use of target terms (terms most appropriate to each animation type). RESULTS: Accuracy on all three conditions discriminated behavioural signs (BS), and (to a lesser degree) paranoid subjects, from the other schizophrenia sub-groups (those in remission and those with passivity features) and the controls. Paranoid and BS groups had difficulties with all the animations, yet all symptom sub-groups failed to use the appropriate mentalising language to describe the ToM animations. CONCLUSIONS: In this first exploration of on-line mentalising abilities in schizophrenia, it is suggested that a failure to use appropriate mentalising language may be a trait marker for the disease. The nature of the type of tasks used to assess social cognitive processing in this group needs careful consideration, and tasks tapping into the fluidity of social interactions yield results that differ from previously reported studies.

Adult↗

Hypoxia increases 25-hydroxycholesterol-induced interleukin-8 protein secretion in human macrophages.

Interleukin-8 (IL-8) is a chemotactic factor for T-lymphocytes and smooth muscle cells and may therefore have an important effect in atherogenesis. It is secreted from oxysterol-containing foam cells which have been found in hypoxic zones in atherosclerotic plaques. The aim of this study was to investigate the effect of hypoxia on the secretion of IL-8 by oxysterol-stimulated macrophages. Hypoxia enhances 25-hydroxycholesterol (25-OH-chol)-induced IL-8 secretion in human monocyte-derived macrophages. The effect is most pronounced when macrophages are incubated with low concentrations of 25-OH-chol. Both 25-OH-chol and hypoxia increases the intracellular level of the signalling molecule hydrogen peroxide (H(2)O(2)). This event coincided with an enhanced binding of the transcription factor c-jun to the IL-8 gene promoter and an increased IL-8 mRNA expression in hypoxic macrophages. These observations suggest that similar intracellular signalling pathways are used for both 25-OH-chol-induced IL-8 expression and hypoxia-induced IL-8 expression. Thus, hypoxia in atherosclerotic plaques may increase the secretion of IL-8 from oxysterol-containing foam cells, which subsequently may accelerate the progression of atherosclerosis.

ATP Synthetase Complexes↗

New insights into the coordination chemistry and molecular structure of copper(II) histidine complexes in aqueous solutions.

Aqueous solutions of Cu2+/histidine (his) (1:2) have been analyzed in parallel with infrared, Raman, ultraviolet/visible/near-infrared, electron spin resonance, and X-ray absorption spectroscopy in the pH range from 0 to 10. Comprehensive interpretation of the data has been used to extract complementary structural information in order to determine the relative abundance of the different complexes. The formation of six different, partly coexisting species is proposed. Structural proposals from literature have been unambiguously confirmed, refined, or, in several cases, corrected. At highly acidic conditions, Cu2+ and his are present as free ions, but around pH = 2, coordination starts via the deprotonated carboxylic acid group. This results in the intermediate species Cu2+[H3his+(Oc)] and Cu2+[H3his+(Oc)]2. The coordination via Oc is attended with a drop in the pKa value of the other receptor groups resulting in a concomitant conversion to the bidentates Cu2+[H2his0(Oc,Nam)] and Cu2+[H2his0(Oc,Nam)]2, with the latter being dominant at pH = 3.5. Coordination of the imidazole ring begins around pH = 3 and leads to the formation of the mixed ligand complexes Cu2+[H2his0(Oc,Nam)][Hhis-(Oc,Nam,Nim)] and Cu2+[Hhis-(Nam,Nim)][Hhis-(Oc,Nam,Nim)] around pH = 5. It is demonstrated that coordination of the imidazole ring occurs predominantly via the N(pi) atom. At pH > 7, the double-tridentate ligand complex Cu2+[Hhis-(Oc,Nam,Nim)]2 is the major species with the N atoms in the equatorial plane and the O atoms in the axial position. This complex decomposes at pH > 10 into a copper oxide/hydroxide precipitate. The overall results provide a consistent picture of the mechanism that drives the coordination and complex formation of the Cu2+/his system.

Journal Article↗

Simultaneous visualization of multiple protein interactions in living cells using multicolor fluorescence complementation analysis.

The specificity of biological regulatory mechanisms relies on selective interactions between different proteins in different cell types and in response to different extracellular signals. We describe a bimolecular fluorescence complementation (BiFC) approach for the simultaneous visualization of multiple protein interactions in the same cell. This approach is based on complementation between fragments of fluorescent proteins with different spectral characteristics. We have identified 12 bimolecular fluorescent complexes that correspond to 7 different spectral classes. Bimolecular complex formation between fragments of different fluorescent proteins did not differentially affect the dimerization efficiency of the bZIP domains of Fos and Jun or the subcellular sites of interactions between these domains. Multicolor BiFC enables visualization of interactions between different proteins in the same cell and comparison of the efficiencies of complex formation with alternative interaction partners.

Animals↗

Ribosome binding to and dissociation from translocation sites of the endoplasmic reticulum membrane.

We have addressed how ribosome-nascent chain complexes (RNCs), associated with the signal recognition particle (SRP), can be targeted to Sec61 translocation channels of the endoplasmic reticulum (ER) membrane when all binding sites are occupied by nontranslating ribosomes. These competing ribosomes are known to be bound with high affinity to tetramers of the Sec61 complex. We found that the membrane binding of RNC-SRP complexes does not require or cause the dissociation of prebound nontranslating ribosomes, a process that is extremely slow. SRP and its receptor target RNCs to a free population of Sec61 complex, which associates with nontranslating ribosomes only weakly and is conformationally different from the population of ribosome-bound Sec61 complex. Taking into account recent structural data, we propose a model in which SRP and its receptor target RNCs to a Sec61 subpopulation of monomeric or dimeric state. This could explain how RNC-SRP complexes can overcome the competition by nontranslating ribosomes.

Animals↗

Impact of chronic obstructive pulmonary disease exacerbations on patients and payers.

Chronic obstructive pulmonary disease (COPD) is not only an established major cause of mortality and morbidity but is increasing in worldwide prevalence despite current medical interventions. The natural history of COPD is punctuated by periods of acute symptomatic, physiologic, and functional deterioration or exacerbations. These events are responsible for considerable additional morbidity and mortality and impact on patients' long-term health status. Despite advances in understanding disease mechanisms and in treatment, exacerbations continue to be the major cause of COPD-associated hospitalization, and provision for their management incurs considerable health care costs. Although pharmacologic therapies may improve clinical outcomes, these benefits must be optimized by prompt diagnosis and delivery. This will require improved understanding of this complex disease by physicians and patients alike.

Disease Progression↗

An advanced test of theory of mind: understanding of story characters' thoughts and feelings by able autistic, mentally handicapped, and normal children and adults.

Research has suggested that the core handicaps of autism result from a specific impairment in theory of mind (ToM). However, this account has been challenged by the finding that a minority of autistic subjects pass 1st- and even 2nd-order ToM tests while remaining socially handicapped. In the present study, able autistic subjects who failed ToM tasks, those who passed 1st-order, and those who passed 2nd-order tasks were tested with a battery of more naturalistic and complex stories. Autistic subjects were impaired at providing context-appropriate mental state explanations for the story characters' nonliteral utterances, compared to normal and mentally handicapped controls. Performance on the stories was closely related to performance on standard ToM tasks, but even those autistic subjects who passed all ToM tests showed impairments on the more naturalistic story materials relative to normal adult controls.

Adolescent↗

Solution structure of the B-Myb DNA-binding domain: a possible role for conformational instability of the protein in DNA binding and control of gene expression.

Double- and triple-resonance heteronuclear NMR spectroscopy have been used to determine the high-resolution solution structure of the minimal B-Myb DNA-binding domain (B-MybR2R3) and to characterize the specific complex formed with a synthetic DNA fragment corresponding to the Myb target site on the Myb-regulated gene tom-1. B-MybR2R3 is shown to consist of two independent protein domains (R2 and R3) joined by a short linker, which have strikingly different tertiary structures despite significant sequence similarities. In addition, the C-terminal region of B-Myb R2 is confirmed to have a poorly defined structure, reflecting the existence of multiple conformations in slow to intermediate exchange. This contrasts with the tertiary structure reported for c-MybR2R3, in which both R2 and R3 have the same fold and the C-terminal region of R2 forms a stable, well-defined helix [Ogata, K., et al. (1995) Nat. Struct. Biol. 2, 309-320]. The NMR data suggest there are extensive contacts between B-MybR2R3 and its DNA target site in the complex and are consistent with a significant conformational change in the protein on binding to DNA, with one possibility being the formation of a stable helix in the C-terminal region of R2. In addition, conformational heterogeneity identified in R2 of B-MybR2R3 bound to the tom-1-A target site may play an important role in the control of gene expression by Myb proteins.

Animals↗

Multimers of the fibroblast growth factor (FGF)-FGF receptor-saccharide complex are formed on long oligomers of heparin.

The minimal signalling unit for tyrosine kinase receptors is two protomers dimerized by one or more ligands. However, it is clear that maximal signalling requires the formation of larger complexes of many receptors at discrete foci on the cell surface. The biological interactions that lead to this are likely to be diverse and have system specific components. In the present study, we demonstrate that, in the FGF (fibroblast growth factor)-FGFR (FGF receptor) system, multimers of the minimal complex composed of two FGF1 and two FGFR2 protomers can form on a single chain of the co-receptor heparin. Using size-exclusion chromatography, we show that two complexes can form on heparin chains as small as 16 saccharide units. We also show by MS that discrete complexes containing exactly two copies of the minimal signalling unit are formed. However, the doublet of complexes appears to be less co-operative than the formation of the 2:2:1 FGF1:FGFR2:heparin complex, suggesting that this mechanism is one of a number of weaker interactions that might be involved in the formation of a focal complex on the cell surface.

Animals↗

Identification of multiprotein complexes containing DNA replication factors by native immunoblotting of HeLa cell protein preparations with T-antigen-dependent SV40 DNA replication activity.

Increasing evidence has supported the concept that many of the enzymes and factors involved in the replication of mammalian DNA function together as a multiprotein complex. We have previously reported on the partial purification of a multiprotein form of DNA polymerase from human HeLa cells shown to be fully competent to support origin-specific large T-antigen-dependent simian virus 40 (SV40) DNA replication in vitro. In an attempt to more definitively identify the complex or complexes responsible for DNA replication in vitro, partially purified human HeLa cell protein preparations competent to replicate DNA in vitro were subjected to native polyacrylamide gel electrophoresis and electrophoretically transferred to nitrocellulose. The Native Western blots were probed with a panel of antibodies directed against proteins believed to be required for DNA replication in vitro. Apparent complexes of 620 kDa and 500 kDa were identified by monoclonal antibodies directed against DNA polymerase alpha and DNA polymerase delta, respectively. To detect epitopes possibly unexposed within the native multiprotein complexes, blots were also analyzed following denaturation in situ following treatment with detergent and reducing agent. The epitope or access to the epitope recognized by the monoclonal antibody against DNA polymerase alpha was destroyed by exposure of the blots to denaturing conditions. In contrast, an epitope present on a very large complex of approximately 1000 kDa was recognized by a monoclonal antibody against proliferating cell nuclear antigen only following treatment of the native immunoblots with denaturing agents. Identification of these complexes will allow their further purification, characterization, and elucidation of their role in the replication of DNA.

DNA Replication↗