Heat treatment of BMP-2 depots on implant materials generates an immobilized layer of BMP-2 with pronounced bioactivity

Bone cells seeded directly on depots of bone morphogenetic protein-2 (BMP-2) increase alkaline phosphatase (ALP) expression. Heating of such BMP-2 depots to 100 degrees C augmented the intensity of this local ALP induction. To understand this unexpected finding, we investigated the effect of heat treatment on BMP-2 depots more closely. Using a novel bioassay based on ALP-induction of remote cells, we found that the amount of released bioactive BMP-2 from heat-treated depots decays within days and could be described by an exponential function. From this function, we expected that pre-incubation of BMP-2 depots in culture medium for 4 weeks renders them insufficient to induce ALP. However, preincubated, heat-treated depots still induced maximal ALP, unless treated with the selective BMP-2 inhibitor noggin. Furthermore, heat treatment of BMP-2 depots generated a layer of immunoreactive BMP-2 at the surface of the carrier. In contrast, BMP-2 was washed off completely if heat treatment of adsorbed protein was omitted. Results show that heat treatment generates both a soluble pool of BMP-2 and a material-bound layer of BMP-2 in which the protein is protected against degradation. Therefore, heat treatment appears useful to locally immobilize BMP-2 on various implant surfaces.     

Clinical and molecular characterization of a near fatal case of human babesiosis in Austria

A previously healthy febrile patient with travel history to Nicaragua showed rapid clinical deterioration with hemodynamic shock and anuria. Diagnosis of severe malaria was established based on intra-erythrocytic parasites and antimalarial treatment was initiated. However, upon reevaluation Babesia microti infection was suspected and molecular characterization by polymerase chain reaction and sequence analysis was performed.     

Dissection of stromal and cancer cell-derived signals in melanoma xenografts before and after treatment with DMXAA

Background:

The non-malignant cells of the tumour stroma have a critical role in tumour biology. Studies dissecting the interplay between cancer cells and stromal cells are required to further our understanding of tumour progression and methods of intervention. For proof-of-principle of a multi-modal approach to dissect the differential effects of treatment on cancer cells and stromal cells, we analysed the effects of the stromal-targeting agent 5,6-dimethylxanthenone-4-acetic acid on melanoma xenografts.

Methods:

Flow cytometry and multi-colour immunofluorescence staining was used to analyse leukocyte numbers in xenografts. Murine-specific and human-specific multiplex cytokine panels were used to quantitate cytokines produced by stromal and melanoma cells, respectively. Human and mouse Affymetrix microarrays were used to separately identify melanoma cell-specific and stromal cell-specific gene expression.

Results:

5,6-Dimethylxanthenone-4-acetic acid activated pro-inflammatory signalling pathways and cytokine expression from both stromal and cancer cells, leading to neutrophil accumulation and haemorrhagic necrosis and a delay in tumour re-growth of 26 days in A375 melanoma xenografts.

Conclusion:

5,6-Dimethylxanthenone-4-acetic acid and related analogues may potentially have utility in the treatment of melanoma. The experimental platform used allowed distinction between cancer cells and stromal cells and can be applied to investigate other tumour models and anti-cancer agents.     

38th Annual Meeting of the International Society of Experimental Hematology

The International Society of Experimental Hematology holds its annual meeting every northern summer. This year the meeting comprised of eight plenary sessions with distinguished invited speakers on in vivo imaging and tracking of hematopoietic stem cells (HSCs), HSC niches, epigenetic regulations of stem cells and regulation of stem cell fate, leukemogenesis, and mesenchymal stem cells. The small size of the meeting (300 attendees) permitted excellent discussion and face-to-face contacts between students, junior scientists and experts. Owing to the large number of keynote speakers, this report focuses on the most novel, unpublished data presented during the meeting.     

Association between dopamine D4 receptor (DRD4) gene polymorphisms and novelty-elicited auditory event-related potentials in preschool children

We investigated associations of the exon III repeat and the -521 C/T polymorphisms of the DRD4 gene with novelty-elicited auditory ERP components and behavioral resistance to distraction in 57 healthy, typically developing 6-year-old children. Dopamine-related gene polymorphisms have previously been linked to processes directing focused attention. We did not find associations between the 7-repeat allele or the T.7 haplotype and the early ERP responses suggesting that DRD4 polymorphisms did not affect the detection of novelty. However, the same polymorphisms affected the late negative components (LN1 and LN2). Late negativities elicited by deviant and novel sounds have been regarded as reflecting reorientation after distraction or additional processing of new information. Children carrying the T.7 haplotype had significantly smaller LN1 and LN2 amplitudes. The presence of the T.7 haplotype also significantly enhanced behavioral resistance to distraction. We suggest that less distraction in T.7 carriers led to less reorienting activity (reflected by the LN components). We also speculate that activation of less sensitive and fewer D4 receptors (as with the T.7 haplotype) is less effective in modulating GABAergic inhibitory signaling, which in turn is reflected in smaller LN amplitudes.     

Continuous EEG monitoring in patients with traumatic brain injury reveals a high incidence of epileptiform activity

BACKGROUND: EEG is the only available method for real time monitoring of the brain and is therefore of great interest in the neurointensive care. The present study describes our experiences from implying continuous EEG monitoring as a routine method. We also present EEG patterns observed on patients with traumatic brain injury (TBI). METHODS: Seventy TBI patients requiring neurointensive care were included. Digital EEG was recorded continuously. Five minutes every hour were analysed off-line. RESULTS: Twenty-three patients (33%) developed seizures, 74+/-47 h after trauma. The seizures were brief, responding to phenytoin, or persistent, requiring propofol or barbiturate sedation. Six out of eight patients with persistent seizures had intracerebral contusions. Eighteen patients (26%) displayed focal high frequency activity that proceeded to seizures in eight cases. Twelve patients (17%) developed recurrent paroxysmal delta activity. The patients in the seizure group were significantly older (62+/-12 vs. 28+/-17 years) and more often exposed to low energy trauma (87% vs 22%) compared to the paroxysmal delta pattern group. CONCLUSION: TBI implies high risk for development of epileptiform activity, with a time lag between trauma and seizure onset. TBI patients also displayed other EEG pattern that should be investigated further in order to obtain a better understanding of posttraumatic mechanisms.     

Newborn infants detect the beat in music

To shed light on how humans can learn to understand music, we need to discover what the perceptual capabilities with which infants are born. Beat induction, the detection of a regular pulse in an auditory signal, is considered a fundamental human trait that, arguably, played a decisive role in the origin of music. Theorists are divided on the issue whether this ability is innate or learned. We show that newborn infants develop expectation for the onset of rhythmic cycles (the downbeat), even when it is not marked by stress or other distinguishing spectral features. Omitting the downbeat elicits brain activity associated with violating sensory expectations. Thus, our results strongly support the view that beat perception is innate.     

„Reversibles posteriores Leukenzephalopathiesyndrom“

We report a case of reversible posterior leukoencephalopathy syndrome in a 50-year-old patient with severe untreated hypertension. Recent advances in magnetic resonance imaging (especially diffusion-weighted imaging) allow new pathopysiological insight: it was found that the resulting vasogenic edema was restricted neither to the posterior vascular territories nor to white matter. The apparent diffusion coefficient helps to differentiate between reversible vasogenic edema and cytotoxic edema, the latter indicating irreversible neuronal death.     

Parkinsonism in a population of northern Tanzania: a community-based door-to-door study in combination with a prospective hospital-based evaluation

The prevalence of Parkinson’s disease (PD) in sub-Saharan Africa is still a matter of debate. The few studies that have been conducted have shown prevalences lower than those in the western world. Whether this represents a genuine finding is unclear to date. In northern Tanzania, we have conducted a hospital-based evaluation and a community-based door-to-door study to assess the prevalence of Parkinsonism, including that of PD. Over a period of 8 months, all patients admitted to a mid-size rural hospital were screened for PD. In parallel, 1,569 people aged ≥50 years were recruited from the communities and assessed for PD with standard questions. Sampling was performed according to the method of “multistage cluster sampling.” The questions had previously been tested in a pilot study prior to the survey. People who screened positive were examined by a specialist neurologist. In the hospital, eight of 740 people with neurological diagnoses had Parkinsonism, of whom three patients had a diagnosis of PD. In the community-based study, 18 people answered positively to least one of the 12 screening questions. However, the diagnosis of PD could not be confirmed by further examination in any of them. The prevalence of PD in northern Tanzania was found to be very low. This result would need confirmation in studies with larger populations, ideally of different African ethnicities.