Cellular dynamics underlying regeneration of damaged axons differs from initial axon development.

While long-distance regeneration may be limited in mammalian species, it is becoming apparent that damaged mature neurons retain some capacity for attempted regeneration and that the adult CNS is not entirely inhibitory to axon growth. Our investigations show that there are critical intrinsic features of postinjury axonal regeneration that differ from initial axon development, and that these distinct differences may account for the limited and inappropriate regenerative response that currently characterizes the mature CNS. We compared the neurochemical and dynamic characteristics of developing axons to relatively mature regenerating axons, utilizing an in vitro model of axonal transection to long-term cultured rat cortical neurons. Immunolabelling studies revealed that regenerating and developing axons have a similar localization of cytoskeletal proteins, but the tips of regenerating axons, although morphologically similar, were smaller with reduced fillopodial extension, relative to developmental growth cones. Live imaging demonstrated that regenerating axons exhibited significantly less outgrowth than developmental neurites. Furthermore, growth cones of regenerating axons had a significant reduction in pausing, considered vital for interstitial branching and pathfinding, than did developmental growth cones. In addition, unlike developing axons, the regenerating axons were unresponsive to the growth factors BDNF and GDNF. Thus, although similar in their cytoskeletal composition, the growth cones of regenerative sprouts differed from their developmental counterparts in their size, their dynamic behaviour and their ability to respond to critical growth factors. These intrinsic differences may account for the inability of post-traumatic locally sprouting axons to make accurate pathway decisions and successfully respond to trauma.

In vitro testing to diagnose venom allergy and monitor immunotherapy: a placebo-controlled, crossover trial.

BACKGROUND: In people with a history of sting allergy, only prior reaction severity and older age are known to predict subsequent reaction risk. Furthermore, no diagnostic test other than a deliberate sting challenge has been found to identify people in whom venom immunotherapy (VIT) has been unsuccessful. OBJECTIVE: We aimed to assess the utility of a number of in vitro tests to diagnose venom allergy and to monitor immunotherapy. METHODS: During a double-blind randomized placebo-controlled crossover trial of Myrmecia pilosula ant VIT the following venom-specific tests were performed at enrolment, and at completion of treatment prior to a diagnostic sting challenge; leucocyte stimulation index (SI), IL-4 production, IgE RAST, histamine release test (HRT), leukotriene release test (LRT) and basophil activation test (BAT). Intradermal venom skin testing (VST) was also performed at trial entry. RESULTS: Only VST and HRT identified those at risk of sting anaphylaxis in the placebo group. Although IgE RAST, leucocyte SI and IL-4 production, LRT and BAT all correlated well with intradermal VSTs, they did not predict sting challenge outcome. After successful VIT, venom-induced leucocyte IL-4 production tended to fall, whereas IgE RAST increased and a natural decline in HRT reactivity was reversed. A confounding seasonal affect on laboratory results was suspected. CONCLUSION: The HRT warrants further assessment for diagnosis of venom allergy. Uninformative performance of the commercially available LRT and BAT tests may be due to pre-incubation with IL-3. None of the tests evaluated appear to be reliable markers of successful VIT.

The accuracy of physical examination to detect abdominal aortic aneurysm.

BACKGROUND: Abdominal palpation during physical examination is an important means of detecting abdominal aortic aneurysm (AAA), but limited information is available on its accuracy. METHODS: Two hundred subjects (aged 51-88 years), 99 with and 101 without AAA as determined by previous ultrasound, each underwent physical examination of the abdomen by 2 internists who were blinded to each other's findings and to the ultrasound diagnosis. RESULTS: The overall accuracy of abdominal palpation for detecting AAA was as follows: sensitivity, 68% (95% confidence interval [CI], 60%-76%); specificity, 75% (95% CI, 68%-82%); positive likelihood ratio, 2.7 (95% CI, 2.0-3.6); negative likelihood ratio 0.43 (95% CI, 0.33-0.56). Interobserver pair agreement for AAA vs no AAA between the first and second examinations was 77% (kappa = 0.53). Sensitivity increased with AAA diameter, from 61% for AAAs of 3.0 to 3.9 cm, to 69% for AAAs of 4.0 to 4.9 cm, 72% for AAAs of 4.0 cm or larger, and 82% for AAAs of 5.0 cm or larger. Sensitivity in subjects with an abdominal girth less than 100 cm (40-in waistline) was 91% vs 53% for girth of 100 cm or greater (P<.001). When girth was 100 cm or greater and the aorta was palpable, sensitivity was 82%. When girth was less than 100 cm and the AAA was 5.0 cm or larger, sensitivity was 100% (12 examinations). Factors independently associated with correct examination findings included AAA diameter (odds ratio [OR], 1.95 per centimeter increase; 95% CI, 1.06-3.58); abdominal girth (OR, 0.90 per centimeter increase; 95% CI, 0.87-0.94); and the examiner's assessment that the abdomen was not tight (OR, 2.68; 95% CI, 1.17-6.13). CONCLUSIONS: Abdominal palpation has only moderate overall sensitivity for detecting AAA, but appears to be highly sensitive for diagnosis of AAAs large enough to warrant elective intervention in patients who do not have a large girth. Abdominal palpation has good sensitivity even in patients with a large girth if the aorta is palpable.

The Adult Attachment Interview and questionnaires for attachment style, temperament, and memories of parental behavior.

Relations between Adult Attachment Interview (AAI) outcomes and data from questionnaires on attachment style, temperament, and memories of parental caregiving behavior were investigated to examine theoretical and methodological specificity of the AAI. The participants were 83 mothers of 1-year-olds. No differences between the three AAI classifications (autonomous, dismissing, or preoccupied) were found. Correlations between scales yielded few significant relations, with the exception of strong relations between some AAI scales for experiences and self-reported memories of parental behavior. The self-report questionnaires for attachment style and memories of parental behavior were therefore found to be not suitable for obtaining information about attachment working models as assessed by the AAI. Furthermore, attachment working models appear independent of temperament.

Localization of a kinesin-related protein to the central pair apparatus of the Chlamydomonas reinhardtii flagellum.

Affinity-purified polyclonal antibodies raised against the conserved motor domain of Drosophila kinesin (alpha HD) recognized a 110 kDa component of the Chlamydomonas flagellar axoneme. Whole-mount immunogold labeling of splayed axonemes showed the striking localization of this antigen along one of the two microtubules of the central pair apparatus. Interestingly, the alpha HD antigen was also localized along the central axis of mutant axonemes lacking the central pair microtubules. These results suggest that a 110 kDa kinesin-related protein is a structural component of the flagellar central pair apparatus and that it is correctly targeted even in the absence of the central pair microtubules.