Perineural infiltration of the inferior alveolar nerve in mandibular ameloblastomas.

Our aim was to evaluate the histological association of mandibular solid and multicystic ameloblastoma with the inferior alveolar nerve, both in situ and in segments of the nerve that had been removed separately, to assess the feasibility of preserving the nerve during resection of mandibular ameloblastomas. In this prospective histological examination of 13 resected hemimandibulectomy specimens, we studied the proximity of tumour cells to the inferior alveolar nerve. In group 1 (n=8) this association was examined with the nerve still within the mandibular segment after resection, while in group 2 (n=5) the nerve was removed from the resected tumour and examined separately.

Early management of gunshot injuries to the face in civilian practice.

Background: Gunshot injuries to the face in civilian practice are rarely reported. Potential complications in the Emergency Department can have catastrophic consequences, and inappropriate operative management of the facial soft and skeletal tissues are related to outcome.

Methods: A structured diagnostic and management approach is used in our Trauma Unit to deal with gunshot wounds to the face.

The role of bacterial and non-bacterial toxins in the induction of changes in membrane transport: implications for diarrhea.

Bacterial toxins induce changes in membrane transport which underlie the loss of electrolyte homeostasis associated with diarrhea. Bacterial- and their secreted toxin-types which have been linked with diarrhea include: (a) Vibrio cholerae (cholera toxin, E1 Tor hemolysin and accessory cholera enterotoxin); (b) Escherichia coli (heat stable enterotoxin, heat-labile enterotoxin and colicins); (c) Shigella dysenteriae (shiga-toxin); (d) Clostridium perfringens (C. perfringens enterotoxin, alpha-toxin, beta-toxin and theta-toxin); (e) Clostridium difficile (toxins A and B); (f) Staphylococcus aureus (alpha-haemolysin); (g) Bacillus cereus (cytotoxin K and haemolysin BL); and (h) Aeromonas hydrophila (aerolysin, heat labile cytotoxins and heat stable cytotoxins).

Quinacrine blocks PrP (106-126)-formed channels.

We investigated the action of the acridine derivative, quinacrine (QC), which has been shown to act as a noncompetitive channel inhibitor. The main effects of QC are voltage- and concentration-dependent changes in the kinetics of the prion protein fragment (PrP[106-126])-formed cation channels. The current-voltage relationships show that the maximal current (I) was not affected whereas the physiologically important mean current (I') was reduced as a result of changes in channel kinetics.

Structural properties of Gerstmann-Straussler-Scheinker disease amyloid protein.

Prion protein (PrP) amyloid formation is a central feature of genetic and acquired forms of prion disease such as Gerstmann-Sträussler-Scheinker disease (GSS) and variant Creutzfeldt-Jakob disease. The major component of GSS amyloid is a PrP fragment spanning residues approximately 82-146. To investigate the determinants of the physicochemical properties of this fragment, we synthesized PrP-(82-146) and variants thereof, including entirely and partially scrambled peptides.

Copper modulation of ion channels of PrP[106-126] mutant prion peptide fragments.

We have shown previously that the protease-resistant and neurotoxic prion peptide fragment PrP[106-126] of human PrP incorporates into lipid bilayer membranes to form heterogeneous ion channels, one of which is a Cu(2+)-sensitive fast cation channel. To investigate the role of PrP[106-126]'s hydrophobic core, AGAAAAGA, on its ability to form ion channels and their regulation with Cu(2+), we used the lipid-bilayer technique to examine membrane currents induced as a result of PrP[106-126] (AA/SS) and PrP[106-126] (VVAA/SSSS) interaction with lipid membranes and channel formation. Channel analysis of the mutant (VVAAA/SSS), which has a reduced hydrophobicity due to substitution of hydrophobic residues with the hydrophilic serine residue, showed a significant change in channel activity, which reflects a decrease in the beta-sheet structure, as shown by CD spectroscopy.

Cu2+-induced modification of the kinetics of A beta(1-42) channels.

We found that the amyloid beta peptide A beta(1-42) is capable of interacting with membrane and forming heterogeneous ion channels in the absence of any added Cu2+ or biological redox agents that have been reported to mediate A beta(1-42) toxicity. The A beta(1-42)-formed cation channel was inhibited by Cu2+ in cis solution ([Cu2+]cis) in a voltage- and concentration-dependent manner between 0 and 250 microM. The [Cu2+]cis-induced channel inhibition is fully reversible at low concentrations between 50 and 100 microM [Cu2+]cis and partially reversible at 250 microM [Cu2+]cis.

Channels formed with a mutant prion protein PrP(82-146) homologous to a 7-kDa fragment in diseased brain of GSS patients.

A major prion protein (PrP) mutant that forms amyloid fibrils in the diseased brain of patients with Gerstmann-Sträussler-Scheinker syndrome (GSS) is a fragment of 7 kDa spanning from residues 81-82 to 144-153 of PrP. Analysis of ionic membrane currents, recorded with a lipid bilayer technique, revealed that the wild-type fragment PrP(82-146) WT and the partially scrambled PrP(82-146) (127-146) SC are capable of forming heterogeneous ion channels that are similar to those channels formed with PrP(106-126). In contrast, PrP(82-146) peptides in which the region from residue 106 to 126 had been scrambled (SC) showed a reduction in interaction with lipid membranes and did not form channels.

Prion channel proteins and their role in vacuolation and neurodegenerative diseases.

The prion encephalopathies, which are characterized by neuropathological changes that include vacuolation, astrocytosis, the development of amyloid plaques and neuronal loss, are associated with the conversion of a normal cellular isoform of prion protein (PrP(c)) to an abnormal pathologic scrapie isoform (PrP(Sc)). The use of PrP[106-126] and its isoforms in studies of channels in lipid bilayers has revealed that it forms heterogeneous channels reflecting modifications in the peptide's structure and differences in the properties of the formed oligomeric aggregates and their intermediates. We propose that the accumulation of pathological isoforms of prion are linked to membrane abnormalities and vacuolation in prion diseases.

Ion channel formation and membrane-linked pathologies of misfolded hydrophobic proteins: the role of dangerous unchaperoned molecules.

1. Protein-membrane interaction includes the interaction of proteins with intrinsic receptors and ion transport pathways and with membrane lipids. Several hypothetical interaction models have been reported for peptide-induced membrane destabilization, including hydrophobic clustering, electrostatic interaction, electrostatic followed by hydrophobic interaction, wedge x type incorporation and hydrophobic mismatch.

Heterogeneous amyloid-formed ion channels as a common cytotoxic mechanism: implications for therapeutic strategies against amyloidosis.

The amyloidoses consist of human and animal chronic, progressive, and sometimes fatal diseases that are characterized by the deposition of insoluble proteinaceous amyloid fibrils in various tissues. Despite the biochemical diversity of amyloids, they share certain properties. The amphipathic and the charged nature of many amyloid-forming peptides point to their intrinsic ability to form diverse beta-sheet-based aggregates and channel types in negatively charged membranes.

Mechanisms of prion-induced modifications in membrane transport properties: implications for signal transduction and neurotoxicity.

Prion-related encephalopathies are associated with the conversion of a normal cellular isoform of prion protein (PrP(c)) to an abnormal pathologic scrapie isoform (PrP(Sc)). The conversion of this single polypeptide chain involves a reduction in the alpha-helices and an increase in beta-sheet content. This change in the content ratio of alpha-helices to beta-sheets may explain the diversity in the proposed mechanisms of action.

Channel activity of deamidated isoforms of prion protein fragment 106-126 in planar lipid bilayers.

Using the lipid bilayer technique, we have found that age-related derivatives, PrP[106-126] (L-Asp108) and PrP[106-126] (L-iso-Asp108), of the prion protein fragment 106-126 (PrP[106-126] (Asn108)) form heterogeneous ion channels. The deamidated isoforms, PrP[106-126] (L-Asp108) and PrP[106-126] (L-iso-Asp108), showed no enhanced propensity to form heterogeneous channels compared with PrP[106-126] (Asn108). One of the PrP[106-126] (L-Asp108)- and PrP[106-126] (L-iso-Asp108)-formed channels had three kinetic modes.

Diversity of amyloid beta protein fragment [1-40]-formed channels.

1. The lipid bilayer technique was used to characterize the biophysical and pharmacological properties of several ion channels formed by incorporating amyloid beta protein fragment (AbetaP) 1-40 into lipid membranes. Based on the conductance, kinetics, selectivity, and pharmacological properties, the following AbetaP[1-40]-formed ion channels have been identified: (i) The AbetaP[1-40]-formed "bursting" fast cation channel was characterized by (a) a single channel conductance of 63 pS (250/50 mM KCl cis/trans) at +140 mV.

Mechanisms of amyloid beta protein-induced modification in ion transport systems: implications for neurodegenerative diseases.

1. Alzheimer's disease (AD) is a neurodegenerative disorder that affects the cognitive function of the brain. Pathological changes in AD are characterized by the formation of amyloid plaques and neurofibrillary tangles as well as extensive neuronal loss.

Properties and modulation of alpha human atrial natriuretic peptide (alpha-hANP)-formed ion channels.

Using the lipid bilayer technique we have optimized recording conditions and confirmed that alpha human atrial natriuretic peptide [alpha-hANP(1-28)] forms single ion channels. The single channel currents recorded in 250/50 mM KCl cis/trans chambers show that the ANP-formed channels were heterogeneous, and differed in their conductance, kinetic, and pharmacological properties. The ANP-formed single channels were grouped as: (i) H202- and Ba2+-sensitive channel with fast kinetics; the nonlinear current-voltage (I-V) relationship of this channel had a reversal potential (Erev) of -28.

Protein aggregation and deposition: implications for ion channel formation and membrane damage.

Protein deposition, aggregation, and formation of amyloids are associated with a wide range of pathologies, including several neurodegenerative diseases. Aggregation and deposition are a result of malfunction in protein folding, assembly, and transport, caused by protein mutation and/or changes in the cell environment. The mechanism of protein deposition and aggregation is triggered when the hydrophobic and positively charged regions of the misfolded proteins are exposed.

Prion peptide fragment PrP[106-126] forms distinct cation channel types.

Using the lipid bilayer technique we have optimized the recording conditions and confirmed that PrP[106-126] (KTNMKHMAGAAAAGAVVGGLG) forms single ion channels. Based on the conductance and kinetic parameters of the single channel currents recorded in 250/50 mM KCl cis/trans we have found that the PrP[106-126]-formed heterogeneous cation channels that differ in their conductance and kinetic properties. The most frequently observed PrP[106-126]-formed single cation channels were those of: (a) a GSSH- and TEA-sensitive channel with fast kinetics (n = 47).

Biophysical and molecular properties of annexin-formed channels.

The annexins are water soluble proteins possessing a hydrophilic surface, which belong to a family of proteins which (a) bind ('annex') both calcium and phospholipids, and (b) form voltage-dependent calcium channels within planar lipid bilayers. Annexins types are diverse (94 annexins in 45 species) and they belong to an enormous multigene family that ranges throughout all eukaryotic kingdoms. Although the structure of these proteins is now well known their functional and physiological roles remain largely unknown and circumstantial.

Properties of cytotoxic peptide-formed ion channels.

Cytotoxic peptides are relatively small cationic molecules such as those found 1) in venoms, e.g., melittin in bee, scorpion toxins in scorpion, pilosulin 1 in jumper ant, and lycotoxin I and II in wolf spider; 2) in skin secretions (e.

Temperatures in and around mandibular fractures.

This study measured the temperature in and around mandibular fractures in 20 anaesthetized patients. A fine calibrated thermocouple attached to a digital thermometer was used to measure temperature at the bone surface margin of a mandibular fracture and 5 and 10 mm from the fracture; within the fracture against the bone at 5, 7 and 10 mm depths and at the base of 7 mm deep biopsy cavities 5 and 10 mm distant from the fracture line immediately after biopsy, then 1 and 2 min later. On the surface the temperature was approximately 1 degrees C warmer than at the 5 and 10 mm sites distant from the fracture.

A component of platypus (Ornithorhynchus anatinus) venom forms slow-kinetic cation channels.

The lipid bilayer technique is used to examine the biophysical properties of anion and cation channels frequently formed by platypus (Ornithorhynchus anatinus) venom (OaV). The OaV-formed anion channel in 250/50 mm KCl cis/trans has a maximum conductance of 857 +/- 23 pS (n = 5) in 250/50 mm KCl cis/trans. The current-voltage relationship of this channel shows strong inward rectification.

Hydrogen peroxide inhibits chloride channels of the sarcoplasmic reticulum of skeletal muscle.

Data obtained with the lipid bilayer technique indicate that cis (cytoplasmic) concentration of 4.4-22 mm hydrogen peroxide (H(2)O(2)), is a water-soluble oxidant. [H(2)O(2)](cis) (n = 26) reversibly inhibits the multisubconductance SCl channel of the sarcoplasmic reticulum vesicles from rabbit skeletal muscle.

Calcium dependence of C-type natriuretic peptide-formed fast K(+) channel.

The lipid bilayer technique was used to characterize the Ca(2+) dependence of a fast K(+) channel formed by a synthetic 17-amino acid segment [OaCNP-39-(1-17)] of a 39-amino acid C-type natriuretic peptide (OaCNP-39) found in platypus (Ornithorhynchus anatinus) venom (OaV). The OaCNP-39-(1-17)-formed K(+) channel was reversibly dependent on 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-buffered cis (cytoplasmic) Ca(2+) concentration ([Ca(2+)](cis)). The channel was fully active when [Ca(2+)](cis) was >10(-4) M and trans (luminal) Ca(2+) concentration was 1.

Characterization of a C-type natriuretic peptide (CNP-39)-formed cation-selective channel from platypus (Ornithorhynchus anatinus) venom.

1. The lipid bilayer technique is used to characterize the biophysical and pharmacological properties of a novel, fast, cation-selective channel formed by incorporating platypus (Ornithorhynchus anatinus) venom (OaV) into lipid membranes. 2.