Cytoskeletal rearrangement by oxidative stress

The cytoskeleton is susceptible to oxidative stress and this occurs prior to membrane blebbing and cell lysis. Vimentin intermediary filaments in rheumatoid synoviocytes are more susceptible than in normal synoviocytes and this may have pathological significance. They are however no more susceptible to heat shock than other cell types.     

Cervical soft tissue imaging using a mobile CBCT scanner with a flat panel detector in comparison with corresponding CT and MRI data sets.

OBJECTIVE: The aim of this study was to evaluate soft tissue image quality of a mobile cone-beam computed tomography (CBCT) scanner with an integrated flat-panel detector. STUDY DESIGN: Eight fresh human cadavers were used in this study. For evaluation of soft tissue visualization, CBCT data sets and corresponding computed tomography (CT) and magnetic resonance imaging (MRI) data sets were acquired. Evaluation was performed with the help of 10 defined cervical anatomical structures. RESULTS: The statistical analysis of the scoring results of 3 examiners revealed the CBCT images to be of inferior quality regarding the visualization of most of the predefined structures. Visualization without a significant difference was found regarding the demarcation of the vertebral bodies and the pyramidal cartilages, the arteriosclerosis of the carotids (compared with CT), and the laryngeal skeleton (compared with MRI). Regarding arteriosclerosis of the carotids compared with MRI, CBCT proved to be superior. CONCLUSIONS: The integration of a flat-panel detector improves soft tissue visualization using a mobile CBCT scanner.     

Clinical indications and perspectives for intraoperative cone-beam computed tomography in oral and maxillofacial surgery.

OBJECTIVES: Intraoperative cone-beam computerized tomography (CBCT) imaging has been introduced in oral and maxillofacial surgery. Using midfacial fractures as the pioneer model, this study describes the spectrum of further promising clinical indications for intraoperative CBCT and a clinical combination with intraoperative navigation. STUDY DESIGN: One hundred seventy-nine patients admitted for surgical treatment of the facial skeleton were included in the study. Intraoperatively, 3-dimensional images were generated with the mobile CBCT scanner Arcadis Orbic 3D, obtained from Siemens Medical Solutions, in a variety of indications. RESULTS: The acquisition of the data sets was uncomplicated, and image quality was sufficient to assess the postoperative result in all cases. In the example of a facial gunshot injury, a navigation system for intraoperative localization of the metal foreign bodies was used.     

Histamine and tryptase modulate asthmatic airway smooth muscle GM-CSF and RANTES release.

Degranulating mast cells are increased in the airway smooth muscle (ASM) of asthmatics, where they may influence ASM function. The aim of the present study was to determine whether histamine and tryptase modulate ASM cell granulocyte-macrophage colony-stimulating factor (GM-CSF) and RANTES (regulated on activation, normal T-cell expressed and secreted) release and also to examine which receptors are involved in this release. Confluent, quiescent ASM cells from asthmatic and nonasthmatic donors were treated with histamine (1 microM-100 microM) with and without histamine receptor antagonist pre-treatment, or the protease-activated receptor (PAR)-2 agonists tryptase (0.5-5 nM) and SLIGKV (100 and 400 microM). The cells were then stimulated with interleukin (IL)-1beta and/or tumour necrosis factor (TNF)-alpha (10 ng.mL(-1)) or left unstimulated for 24 h. Release of GM-CSF and RANTES was determined by ELISA and prostaglandin (PG)E(2) measured by enzyme immunoassay. Neither histamine nor tryptase induced ASM GM-CSF or RANTES secretion. However, histamine increased IL-1beta-induced GM-CSF release and markedly reduced TNF-alpha-induced RANTES release by both asthmatic and nonasthmatic cells to a similar extent, but did not modulate PGE(2) release. All changes involved activation of the histamine H1 receptor as they were partially or fully blocked by chlorpheniramine, but not ranitidine. Tryptase, via its proteolytic activity, also potentiated GM-CSF, but not RANTES, release from asthmatic and nonasthmatic ASM cells induced by both cytokines. PAR-2 involvement in the tryptase potentiation was unlikely because SLIGKV had no effect. In conclusion, mast cells, through histamine and tryptase, may locally modulate airway smooth muscle-induced inflammation in asthma.     

Gonococcal opacity: lectin-like interactions between Opa proteins and lipooligosaccharide.

Previous evidence from our laboratory suggested that the tight intercellular adhesions between the outer membranes of gonococci displaying the opacity colony phenotype occurred because Opa proteins expressed on one gonococcus adhered to the lipooligosaccharide (LOS) of the opposing bacterium (M.S. Blake, p. 51-66, in G. G. Jackson and H. Thomas, ed., The Pathogenesis of Bacterial Infections, 1985, and M. S. Blake and E. C. Gotschlich, p. 377-400, in M. Inouye, ed., Bacterial Outer Membranes as Model Systems, 1986). A noncompetitive inhibition assay used previously to determine the carbohydrate structures recognized by the major hepatic asialoglycoprotein receptor was modified to determine the gonococcal LOS structures that bind Opa proteins (R. T. Lee, Targeted Diagn. Ther. Ser. 4:65-84, 1991). The LOS carbohydrates used in these assays were LOS structures purified from pyocin LOS mutants of Neisseria gonorrhoeae 1291 described by K. C. Dudas and M. A. Apicella (Infect. Immun. 56:499-504, 1988) and further characterized by C. M. John et al. (J. Biol. Chem. 266:19303-19311, 1991). Purified gonococcal Opa proteins were incubated with each of the parent and mutant LOS, and the amount of binding of Opa proteins was measured by a direct enzyme-linked immunosorbent assay using the Opa-specific monoclonal antibody 4B12. The affinities of the Opa proteins for each of the LOS were determined indirectly by measuring the concentrations of Opa proteins that noncompetitively inhibited 50% of the binding of LOS-specific monoclonal antibodies. This concentration is inversely proportional to the affinity of the inhibitor (R. T. Lee, Targeted Diagn. Ther. Ser. 4:65-84, 1991). Our data suggest that the gonococcal Opa proteins tested had the highest affinity for the Gal beta 1-4GlcNAc residue present on the gonococcal lactoneoseries LOS. This affinity was comparable to that reported for the binding of the major hepatic asialoglycoprotein receptor to glycoconjugates containing terminal galactose and N-acetylgalactosamine (R. T. Lee, Targeted Diagn. Ther. Ser. 4:65-84, 1991). After sialylation of the lactoneoseries LOS, presumably on the terminal galactose residue, the interaction with the Opa proteins was ablated. Therefore, the gonococcal Opa-LOS and mammalian epithelial cell asialoglycoprotein receptor-carbohydrate interactions have quite similar specificities.     

INTERACTIONS BETWEEN THE CIRCULATORY EFFECTS OF CENTRAL HYPOVOLAEMIA AND ARTERIAL HYPOXIA IN CONSCIOUS RABBITS

1. Eight conscious rabbits were repeatedly subjected to progressive reduction in central blood volume by gradually inflating a thoracic inferior vena caval-cuff so cardiac index (CI) fell at a constant 8.5% of baseline/min. 2. Caval-cuff inflations were performed after 10 min exposure to 100, 21, 12–14 and 8–10% O₂, with and without the addition of 3–4% CO₂, in randomized order. 3. The haemodynamic response to progressive reduction in central blood volume was biphasic. In Phase I, systemic vascular conductance index (SVCI) fell linearly, supporting mean arterial pressure (MAP). When CI had fallen to a critical level, Phase II occurred in which SVCI rose abruptly, MAP plummeted and respiratory drive progressively increased. 4. During Phase I, there were independent linear relationships between Pao₂ (but not Pao₂) and the rates at which SVCI and MAP changed during the progressive fall of CI. The higher the level of Pao₂, the greater was the rate of fall of SVCI and the less the rate of fall of MAP. 5. There was an inverted U-shaped effect of Pao₂, on the level of CI at which Phase II occurred: (a) during hyperoxia (100% O₂), Phase II occurred later than during normoxia (21% O₂); and (b) across the normoxic and hypoxic gas mixtures (21–8% O₂, with and without added CO₂), there was an independent linear relationship between Pao₂ (but not Pao₂ or Pao₂×Pao₂) and the level of CI at which Phase II occurred. That is, the lower the level of Pao₂, the later was the onset of Phase II. This interaction is best explained by an increased level of central sympathetic vasoconstrictor drive during hypoxia.     

VASOCONSTRICTION IN THE RENAL VASCULAR BED DURING EXERCISE: STUDIES IN CONTROL AND HEART FAILURE RABBITS

1. The effects of graded treadmill exercise on renal blood flow (RBF) were examined in seven rabbits, in which congestive heart failure (CHF) was produced by the administration of doxorubicin, 1 mg/kg, twice weekly for 8 weeks, and in seven controls. A third group of five rabbits underwent doxorubicin treatment with the addition of surgical section of the left renal sympathetic nerve. 2. During submaximal exercise, there was a small reduction in RBF in controls, which was greatly exaggerated in CHF. 3. In both control and heart failure rabbits, there was a precipitous fall in RBF as exercise fatigue developed. 4. Renal sympathectomy ablated these changes in RBF during exercise. 5. It is concluded that in heart failure there is an exaggerated, sympathetically mediated, diversion of blood flow away from the kidney. The onset of exercise fatigue in both normal and heart failure rabbits is accompanied by a marked intensification of this process.     

Atlantoaxial instability in Down's syndrome: clinical and radiological screening

One hundred and thirty children with Down's syndrome were screened for the presence of atlantoaxial instability, using both clinical examination and radiographs of the cervical spine taken in flexion and hyperextension views. Seven children were found to have radiological evidence of atlantoaxial instability, with an atlanto-dens interval greater than 5.0 mm in one or all positions. Although a full clinical history was obtained from the attending parent and each child underwent a complete neurological examination, there were no factors detected which differentiated between those with radiological evidence of atlantoaxial instability and those with a normal atlantodens distance. It is recommended that children with Down's syndrome be screened twice, at the ages of 5-10 years and at 15 years.