SI12Lymphocyte Subsets Following Autologous Transfer of CD25 Depleted Leukapheresis Products

The CXCL12/CXCR4 chemokine axis is a well characterized and important chemotactic stimulus/receptor unit that orchestrates the homing and migration of cells to the bone marrow and to ischemic tissues following tissue damage. Here, we demonstrate that the sialomucin, CD164, a regulator of haemopoietic precursor cell adhesion to stroma and entry of primitive CD34⁺CD38^lo/‐ precursor cells into cycle, modulates the migration of CD133⁺ cord blood cells to CXCL12 by associating with the CXCR4 receptor. This was demonstrated by a reduction in CD133⁺ cell migration on fibronectin to CXCL12 (i) by engaging the functional class II glycosylation‐dependent epitope on CD164 with the 103B2/9E10 class II but not the N6B6 class III antibody; and (ii) by RNAi knockdown of CD164 protein levels in CD133⁺ cells. The inhibition of migration was more pronounced in the more primitive CD34⁺CD38^lo/‐ cell subset. Similar studies using the Jurkat cell line confirmed these findings and led to further analyses using alternative chemokines. A direct association between CXCR4 and CD164 was demonstrated by the co‐localisation of CD164 with CXCR4 and VLA‐4 and VLA‐5 at the leading edge of CD133⁺ cells when CXCL12 was presented on fibronectin. This was further supported by immunoprecipitation studies that demonstrate in the absence of CXCL12, CXCR4 is associated only with VLA‐4 and VLA‐5 but on exposure to CXCL12, CD164 is rapidly recruited to the CXCR4 complex. Knock‐down of CD164 using siRNA revealed that signalling through CXCR4 via PKC‐ζ was significantly dampened. Our findings therefore support a novel association between three distinct families of cell surface receptors that regulate both cell migratory and proliferative responses and identify a CD164 as a key regulator of the CXCL12/CXCR4 axis.     

Oculomotor nerve palsy due to thrombosis of a posterior communicating artery aneurysm following diagnostic angiography

We present a patient who developed a painful third nerve galsy two days after angiography had demonstrated a large aneurysm on the P1 segment of the left posterior cerebral artery. CT at this stage demonstrated extensive thrombus within the previously uncomplicated aneurysm. The haemodynamics of this aneurysm resulted in incomplete clearance of contrast medium from its fundus and we posit that this may have promoted thrombus formation. Six months later the aneurysm was shown angiographically to be completely occluded.     

Anaesthetic potency of inhalation agents is independent of membrane microviscosity

The decrease in membrane microviscosity of erythrocyte ghosts in the presence of clinically relevant concentrations of seven inhalation anaesthetic agents was studied using fluorescence polarization anisotropy of the membrane incorporated fluorescent probes 1,6-diphenyl- 1,3,5-hexatriene and 1-[4-trimethylammoniumphenyl]-6-phenyl-1,3,5- hexatriene. All anaesthetic agents produced a dose-dependent decrease in anisotropy of both probes, indicating decreased membrane microviscosity. The reduction in anisotropy measured at the minimum alveolar concentration (ED50) for anaesthesia was related inversely to the anaesthetic potency of the agent and was directly proportional to the hypothetical concentration of agent in the membrane calculated from lipid-water partition coefficients. These findings do not support the hypothesis that volatile anaesthetic agents act by increasing membrane microviscosity of the bulk lipid bilayer to produce anaesthesia.      

Assessment of fetal well-being with magnetic resonance.

The application of magnetic resonance techniques in the assessment of fetal growth, fetal growth patterns and fetal health was assessed. Eighty-four sets of fetal images were obtained using a fast-scan magnetic resonance imaging technique. Measurements were made of fetal subcutaneous fat thickness, uterine cavity length and width, fetal and uterine cross-sectional areas and fetal volume. Fetal area and fetal volume measurements were found to correlate well with birth weight. Measurement of subcutaneous fat thickness may prove to be a means of differentiating between those fetuses who are constitutionally as opposed to pathologically large or small. Thirteen women had additional spectroscopic studies carried out. Twelve of the women had normal pregnancies. One woman had a twin pregnancy in which one twin died. 31P phosphorus spectra were obtained from seven of the normal pregnancies. In the remainder, the depth of the abdominal wall prevented spectra being obtained from the placenta. Differences in phosphorus metabolites were obtained from the placenta of the dead twin compared to those from the healthy pregnancies.     

The amplitude modulation-following response as an audiometric tool.

The amplitude modulation-following response (AMFR) is an auditory scalp-recorded potential, evoked using continuous, amplitude-modulated tones. The current study was designed to explore the audiometric utility of the AMFR by demonstrating the frequency specificity of the response and assessing the relation between behaviorally measured pure-tone thresholds and AMFR detection thresholds. Subjects in this study were six normal-hearing and four hearing-impaired adults. High-pass masking results in the normal hearing subjects demonstrated that the AMFR is associated with a narrow range of activation along the cochlea around the carrier frequency. Frequency-specific results from the hearing-impaired subjects confirmed this finding. Thresholds for the AMFR, defined in spectral terms, were consistent with the behavioral estimates in both the normal and the hearing-impaired subjects.