Reconstitution of the central and peripheral nervous system during salamander tail regeneration

We show that after tail amputation in Ambystoma mexicanum (Axolotl) the correct number and spacing of dorsal root ganglia are regenerated. By transplantation of spinal cord tissue and nonclonal neurospheres, we show that the central spinal cord represents a source of peripheral nervous system cells. Interestingly, melanophores migrate from preexisting precursors in the skin. Finally, we demonstrate that implantation of a clonally derived spinal cord neurosphere can result in reconstitution of all examined cell types in the regenerating central spinal cord, suggesting derivation of a cell with spinal cord stem cell properties.     

Variation in inflammatory/regulatory cytokines in secondary, tertiary, and quaternary challenges with dengue virus

Abstract. Secondary heterologous dengue infection is a risk factor for severe disease manifestations because of the immune-enhancement phenomenon. Succeeding clinical infections are seldom reported, and the clinical course of tertiary and quaternary dengue infections is not clear. Cuba represents a unique environment to study tertiary/quaternary dengue infections in a population with known clinical and serologic dengue markers and no dengue endemicity. We took advantage of this exceptional epidemiologic condition to study the effect of primary, secondary, tertiary, and quaternary dengue infection exposure on the expression of pro-inflammatory and regulatory cytokines, critical in dengue infection pathogenesis, by using a dengue infection ex vivo model. Whereas secondary exposure induced a high cytokine response, we found a significantly lower expression of tumor necrosis factor-α, interferon-γ, interleukin-10, and tumor growth factor-β after tertiary and quaternary infectious challenge. Significant differences in expression of the cytokines were seen between the dengue immune profiles, suggesting that the sequence in which the immune system encounters serotypes may be important in determining the nature of the immune response to subsequent infections.     

Lymphoid progenitors in normal mouse lymph nodes develop into NK cells and T cells in vitro and in vivo

We have identified a population of normal mouse LN cells, termed LN lymphoid progenitor (LNLP), resembling common lymphoid progenitor (CLP) in the bone marrow. LNLPs lack lineage markers and express CD127, low levels of CD117 (c-Kit), and Sca-1, but lack fms-related tyrosine kinase 3. They efficiently differentiate in vitro into natural killer (NK) cells and T cells, but not mature B cells. LNLPs injected into nonirradiated lymphopenic mice that have no LN develop into mostly splenic T cells with low numbers of NK cells and B cells. When injected into irradiated mice, they generate NK cells and T cells, but not B cells, in the LN. By contrast, bone marrow CLPs develop into mostly B cells with very small numbers of T and NK cells in recipients' spleen and LN. LNLPs have NK and T-cell potentials, but little B-cell potential, and they can develop into NK cells within the LN of normal mice, but their contribution to the T-cell lineage is unknown.     

Comparative developmental biology of the uterus: insights into mechanisms and developmental disruption

The uterus is an essential organ for reproduction in mammals that derives from the Müllerian duct. Despite the importance of the uterus for the fertility and health of women and their offspring, relatively little is known about the hormonal, cellular and molecular mechanisms that regulate development of the Müllerian duct and uterus. This review aims to summarize the hormonal, cellular and molecular mechanisms and pathways governing development of the Müllerian duct and uterus as well as highlight developmental programming effects of endocrine disruptor compounds. Organogenesis, morphogenesis, and functional differentiation of the uterus are complex, multifactorial processes. Disruption of uterine development in the fetus and neonate by genetic defects and exposure to endocrine disruptor compounds can cause infertility and cancer in the adult and their offspring via developmental programming. Clear conservation of some factors and pathways are observed between species; therefore, comparative biology is useful to identify candidate genes and pathways underlying congenital abnormalities in humans.     

Sequelae of a left-sided parietal stroke: Posterior alien hand syndrome

Posterior alien hand syndrome is a new addition to a poorly understood group of movement disorders. Historically, anatomical lesions causing uncontrolled limb movement and a feeling of foreignness were found to be located in the corpus callosum or frontal lobe. Recent case reports, however, demonstrate the typical symptoms of alien hand syndrome with lesions located in the parietal/occipital lobes. Disturbance of normal function in these regions tends to produce less complex motor activity, such as hand levitation, along with a sensory component characterized by feeling of estrangement. We discuss a patient who presented with unusual symptoms following an outpatient procedure and was found to have posterior alien hand syndrome.     

Self-referential processing influences functional activation during cognitive control: an fMRI study

Rostral anterior cingulate cortex (rACC) plays a central role in the pathophysiology of major depressive disorder (MDD). As we reported in our previous study (Wagner et al., 2006), patients with MDD were characterized by an inability to deactivate this region during cognitive processing leading to a compensatory prefrontal hyperactivation. This hyperactivation in rACC may be related to a deficient inhibitory control of negative self-referential processes, which in turn may interfere with cognitive control task execution and the underlying fronto-cingulate network activation. To test this assumption, a functional magnetic resonance imaging study was conducted in 34 healthy subjects. Univariate and functional connectivity analyses in statistical parametric mapping software 8 were used. Self-referential stimuli and the Stroop task were presented in an event-related design. As hypothesized, rACC was specifically engaged during negative self-referential processing (SRP) and was significantly related to the degree of depressive symptoms in participants. BOLD signal in rACC showed increased valence-dependent (negative vs neutral SRP) interaction with BOLD signal in prefrontal and dorsal anterior cingulate regions during Stroop task performance. This result provides strong support for the notion that enhanced rACC interacts with brain regions involved in cognitive control processes and substantiates our previous interpretation of increased rACC and prefrontal activation in patients during Stroop task.     

Subarachnoid haemorrhage WFNS grade V: is maximal treatment worthwhile?

Background

Aneurysmal subarachnoid haemorrhage (SAH) WFNS grade V is commonly known to be associated with high mortality and a very poor prognosis for survivors. Therefore, maximal invasive therapy is frequently delayed until any spontaneous improvement with or without an external ventricular drainage occurs. The aim of the study was to verify possible predictive factors and the probability of a favourable outcome in maximally treated patients.

Methods

One hundred and thirty-eight consecutive patients with WFNS grade V SAH were admitted between 03/2006 and 12/2010. Thirty-five patients died before aggressive therapy could proceed. One hundred and three patients received maximal treatment and were retrospectively evaluated. The outcome was assessed at discharge and in the follow-up with the Glasgow Outcome Scale. Univariate and multivariate linear regression models were performed to find predictors for an unfavourable outcome.

Results

Despite treatment, early mortality was 30 % (n?=?31). At discharge, the rate of both vegetative and severely disabled patients was 27 % (n?=?28). Favourable outcome at discharge was observed in 16 % (n?=?16) of cases, whereas in the follow-up it rose to 26 % (n?=?27). Multivariate full model regression identified intraventricular haematoma (IVH) and increasing age as independently predictive for poor outcome.

Conclusions

Despite treatment, initial mortality and severe disability remain high. Nevertheless, a favourable outcome was achieved in 26 % of aggressively treated patients, rendering the withdrawal of maximal therapy for WFNS grade V SAH patients unacceptable today. In cases of old patients with IVH, the indication for aggressive therapy should be put in place more carefully due to a very poor prognosis.