Granulocyte colony-stimulating factor supports liver regeneration in a small-for-size liver remnant mouse model

Experimental partial hepatectomy of more than 80% of the liver weight bears an increased mortality in rodents, due to impaired hepatic regeneration in small-for-size liver remnants. Granulocyte colony-stimulating factor (G-CSF) promotes progenitor cell expansion and mobilization and also has immunomodulatory properties. The aim of this study was to determine the effect of systemically administered G-CSF on liver regeneration and animal survival in a small-for-size liver remnant mouse model. Mice were preconditioned daily for 5 days with subcutaneous injections of 5 microg G-CSF or aqua ad injectabile. Subsequently, 83% partial hepatectomy was performed by resecting the median, the left, the caudate, and the right inferior hepatic lobes in all animals. Daily sham or G-CSF injection was continued. Survival was significantly better in G-CSF-treated animals (P < 0.0001). At 36 and 48 h after microsurgical hepatic resection, markers of hepatic proliferation (Ki67, BrdU) were elevated in G-CSF-treated mice compared to sham injected control animals (P < 0.0001) and dry liver weight was increased (P < 0.05). G-CSF conditioning might prove to be useful in patients with small-for-size liver remnants after extended hepatic resections due to primary or secondary liver tumors or in the setting of split liver transplantation.

Differential effect of side of temporal lobe epilepsy on lateralization of hippocampal, temporolateral, and inferior frontal activation patterns during a verbal episodic memory task

The encoding of verbal stimuli elicits left-lateralized activation patterns within the medial temporal lobes in healthy adults. In our study, patients with left- and right-sided temporal lobe epilepsy (LTLE, RTLE) were investigated during the encoding and retrieval of word-pair associates using functional magnetic resonance imaging. Functional asymmetry of activation patterns in hippocampal, inferior frontal, and temporolateral neocortical areas associated with language functions was analyzed. Hippocampal activation patterns in patients with LTLE were more right-lateralized than those in patients with RTLE (P<0.05). There were no group differences with respect to lateralization in frontal or temporolateral regions of interest (ROIs). For both groups, frontal cortical activation patterns were significantly more left-lateralized than hippocampal patterns (P<0.05). For patients with LTLE, there was a strong trend toward a difference in functional asymmetry between the temporolateral and hippocampal ROIs (P=0.059). A graded effect of epileptic activity on laterality of the different regional activation patterns is discussed.

Liver repopulation with bone marrow derived cells improves the metabolic disorder in the Gunn rat

BACKGROUND: Reversible ischaemia/reperfusion (I/R) liver injury has been used to induce engraftment and hepatic parenchymal differentiation of exogenous beta2-microglubulin(-)/Thy1(+) bone marrow derived cells. AIM: To test the ability of this method of hepatic parenchymal repopulation, theoretically applicable to clinical practice, to correct the metabolic disorder in a rat model of congenital hyperbilirubinaemia. METHODS AND RESULTS: Analysis by confocal laser microscopy of fluorescence labelled cells and by immunohistochemistry for beta2-microglubulin, 72 hours after intraportal delivery, showed engraftment of infused cells in liver parenchyma of rats with I/R, but not in control animals with non-injured liver. Transplantation of bone marrow derived cells obtained from GFP-transgenic rats into Lewis rats resulted in the presence of up to 20% of GFP positive hepatocytes in I/R liver lobes after one month. The repopulation rate was proportional to the number of transplanted cells. Infusion of GFP negative bone marrow derived cells into GFP positive transgenic rats resulted in the appearance of GFP negative hepatocytes, suggesting that the main mechanism underlying parenchymal repopulation was differentiation rather than cell fusion. Transplantation of wild type bone marrow derived cells into hyperbilirubinaemic Gunn rats with deficient bilirubin conjugation after I/R damage resulted in 30% decrease in serum bilirubin, the appearance of bilirubin conjugates in bile, and the expression of normal UDP-glucuronyltransferase enzyme evaluated by polymerase chain reaction. CONCLUSIONS: I/R injury induced hepatic parenchymal engraftment and differentiation into hepatocyte-like cells of bone marrow derived cells. Transplantation of bone marrow derived cells from non-affected animals resulted in the partial correction of hyperbilirubinaemia in the Gunn rat.

Emphysema and secondary pneumothorax in young adults smoking cannabis

BACKGROUND: We observed a remarkable increase in the number of young patients who presented with lung emphysema and secondary spontaneous pneumothorax (SSP) at our institution for over a period of 30 months; most of them have a common history of marijuana abuse. STUDY DESIGN: Retrospective case series. METHODS: Seventeen young patients presented with spontaneous pneumothorax with bullous lung emphysema were systematically evaluated over a period of 30 months. All were regular marijuana smokers. Clinical history, chest X-ray, CT-scan, lung function test, and laboratory and histological examinations were assessed. We compared the findings of this group (group I) with the findings of non-marijuana smoking patients (group II) in the same period. The findings of this series were also compared with the findings of 75 patients presented with pneumothorax in a previous period from January 2000 till March 2002 (group III). RESULTS: In group I, there were 17 patients: the median age of the patients was 27 years (range 19-43 years), 16 males and 1 female. All were living in Switzerland. All but one smoked marijuana daily for a mean of 8.8 years and tobacco for 11.8 years. CT-scan showed multiple bullae at the apex or significant bullous emphysema with predominance in the upper lobes only in two patients. Only two patients had reduced forced first second expiratory volume (FEV1) and one reduced vital capacity (VC) below the predicted 50%. This correlated with the subjectively asymptomatic condition of the patients. All but two patients were treated by video-assisted thoracoscopic surgery (VATS) for prevention of relapsing pneumothorax. Histology showed severe lung emphysema, inflammation, and heavily pigmented macrophages. In group II, there were 85 patients: there were 78 males, the median age was 24 years (range 17-40 years), 74 patients smoked tobacco for 13.4 years but no marijuana. CT-scan in 72 patients showed only small bullae at the apex but no significant emphysema; other clinical, laboratory, and histopathological findings showed no significant difference in group I. In group III, there were 75 patients: there were 71 males and 4 females. Mean age was 25 years (range 16-46 years). Six smoked marijuana daily for a mean of 3.2 years, and 62 smoked tobacco for 14 years. CT-scan done in 59 patients showed few small bullae at the apex but no significant lung emphysema. The presence of lung emphysema on CT-scan in group I was significantly different than in groups II and III (p=0.14). No significant difference was found among all groups in the form of clinical, laboratory, and histopathological findings. CONCLUSIONS: In case of emphysema in young individuals, marijuana abuse has to be considered in the differential diagnosis. The period of marijuana smoking seems to play an important role in the development of lung emphysema. This obviously quite frequent condition in young and so far asymptomatic patients will have medical, financial, and ethical impact, as some of these patients may be severely handicapped or even become lung transplant candidates in the future.

Ear acupuncture points in neonates

OBJECTIVE: The aim of this study was to determine the presence and absence of acupuncture ear points in healthy neonates. DESIGN: This was a prospective observational study performed at a university teaching hospital. Subjects: The subjects were healthy neonates. We compared male and female neonates, right and left lobe, term and preterm deliveries, and cesarean sections versus vaginal deliveries. Examinations took place on the fifth day after delivery and were performed by a neuronal pen (SVESA 1070, SVESA GmbH, Munich, Germany). An integrated optical signal detected the ear points that were assigned to the Chinese ear map. MAIN OUTCOME MEASURES: This study looked at the presence and absence of acupuncture ear points in neonates. RESULTS: There were 27 male neonates and 23 female neonates. In 66% of neonates, no points at all were found. We detected 0-4 points on the right lobe and 0-2 points on the left lobe. The psychovegetative rim was the most common point in 26% of all children. No psychic points were detected. No significant differences were found between right and left ear lobes, male and female neonates, or term and preterm deliveries with respect to numbers of points or access of points. Moreover, there were no differences among modes of delivery. CONCLUSIONS: Some ear points in healthy neonates are detectable and not dependent on side of the ear lobe. Females had significantly more acupuncture points. There was an extremely significant difference in the group with 2 active earpoints between cesarean and vaginally delivered neonates. The most important point was the psychovegetative rim and the absence of psychic points in favor of the organ points. Possibly, ear points in neonates could be used for diagnostic and therapeutic options in neonates in the future.

AN EXPERIMENTAL STUDY OF PARTIAL LOW RISK DEPLOYMENT IN A FIXED VEHICLE ENVIRONMENT

This study will look at the passenger air bag (PAB) performance in a fix vehicle environment using Partial Low Risk Deployment (PLRD) as a strategy. This development will follow test methods against actual baseline vehicle data and Federal Motor Vehicle Safety Standards 208 (FMVSS 208). FMVSS 208 states that PAB compliance in vehicle crash testing can be met using one of three deployment methods. The primary method suppresses PAB deployment, with the use of a seat weight sensor or occupant classification sensor (OCS), for three-year old and six-year old occupants including the presence of a child seat. A second method, PLRD allows deployment on all size occupants suppressing only for the presents of a child seat. A third method is Low Risk Deployment (LRD) which allows PAB deployment in all conditions, all statures including any/all child seats. This study outlines a PLRD development solution for achieving FMVSS 208 performance. The results of this study should provide an option for system implementation including opportunities for system efficiency and other considerations. The objective is to achieve performance levels similar too or incrementally better than the baseline vehicles National Crash Assessment Program (NCAP) Star rating. In addition, to define systemic flexibility where restraint features can be added or removed while improving occupant performance consistency to the baseline. A certified vehicles’ air bag system will typically remain in production until the vehicle platform is redesigned. The strategy to enable the PLRD hypothesis will be to first match the baseline out of position occupant performance (OOP) for the three and six-year old requirements. Second, improve the 35mph belted 5th percentile female NCAP star rating over the baseline vehicle. Third establish an equivalent FMVSS 208 certification for the 25mph unbelted 50th percentile male. FMVSS 208 high-speed requirement defines the federal minimum crash performance required for meeting frontal vehicle crash-test compliance. The intent of NCAP 5-Star rating is to provide the consumer with information about crash protection, beyond what is required by federal law. In this study, two vehicles segments were used for testing to compare and contrast to their baseline vehicles performance. Case Study 1 (CS1) used a cross over vehicle platform and Case Study 2 (CS2) used a small vehicle segment platform as their baselines. In each case study, the restraints systems were from different restraint supplier manufactures and each case contained that suppliers approach to PLRD. CS1 incorporated a downsized twins shaped bag, a carryover inflator, standard vents, and a strategic positioned bag diffuser to help disperse the flow of gas to improve OOP. The twin shaped bag with two segregated sections (lobes) to enabled high-speed baseline performance correlation on the HYGE Sled. CS2 used an A-Symmetric (square shape) PAB with standard size vents, including a passive vent, to obtain OOP similar to the baseline. The A-Symmetric shape bag also helped to enabled high-speed baseline performance improvements in HYGE Sled testing in CS2. The anticipated CS1 baseline vehicle-pulse-index (VPI) target was in the range of 65-67. However, actual dynamic vehicle (barrier) testing was overshadowed with the highest crash pulse from the previous tested vehicles with a VPI of 71. The result from the 35mph NCAP Barrier test was a solid 4-Star (4.7 Star) respectfully. In CS2, the vehicle HYGE Sled development VPI range, from the baseline was 61-62 respectively. Actual NCAP test produced a chest deflection result of 26mm versus the anticipated baseline target of 12mm. The initial assessment of this condition was thought to be due to the vehicles significant VPI increase to 67. A subsequent root cause investigation confirmed a data integrity issue due to the instrumentation. In an effort to establish a true vehicle test data point a second NCAP test was performed but faced similar instrumentation issues. As a result, the chest deflect hit the target of 12.1mm; however a femur load spike, similar to the baseline, now skewed the results. With noted level of performance improvement in chest deflection, the NCAP star was assessed as directional for 5-Star capable performance. With an actual rating of 3-Star due to instrumentation, using data extrapolation raised the ratings to 5-Star. In both cases, no structural changes were made to the surrogate vehicle and the results in each case matched their perspective baseline vehicle platforms. These results proved the PLRD is viable for further development and production implementation.

Plasma levels of endothelin-1 after a pulmonary embolism of bone marrow fat

BACKGROUND: During orthopedic surgery, embolization of bone marrow fat can lead to potentially fatal, intra-operative cardiovascular deterioration. Vasoactive mediators may also be released from the bone marrow and contribute to these changes. Increased plasma levels of endothelin-1 (ET-1) have been observed after pulmonary air and thrombo-embolism. The role of ET-1 in the development of acute cardiovascular deterioration as a result of bone marrow fat embolization during vertebroplasty was therefore investigated. METHODS: Bone cement was injected into three lumbar vertebrae of six sheep in order to force bone marrow fat into the circulation. Invasive blood pressures and heart rate were recorded continuously until 60 min after the last injection. Cardiac output, arterial and mixed venous blood gas parameters and plasma ET-1 concentrations were measured at selected time points. Post-mortem, lung biopsies were taken for analysis of intravascular fat. RESULTS: Cement injections resulted in a sudden (within 1 min) and severe increase in pulmonary arterial pressure (>100%). Plasma concentrations of ET-1 started to increase after the second injection, but no significant changes were observed. Intravascular fat and bone marrow cells were present in all lung lobes. CONCLUSION: Cement injections into vertebral bodies elicited fat embolism resulting in subsequent cardiovascular changes that were characterized by an increase in pulmonary arterial pressure. Cardiovascular complications as a result of bone marrow fat embolism should thus be considered in patients undergoing vertebroplasty. No significant changes in ET-1 plasma values were observed. Thus, ET-1 did not contribute to the acute cardiovascular changes after fat embolism.

Sellar fracture followed by sudden death: an autopsy case

The authors describe a case of sellar fracture followed by sudden death. The victim was involved in a wrangle. The autopsy revealed facial damage and sellar fracture and no evidence of cerebral damage, except for a mild subarachnoid hemorrhage in the left parietotemporal regions and undersurface of both frontal lobes. Sellar fracture is a rare and severe entity, associated with serious complications, which is frequently diagnosed postmortem. In any case, death is rarely a direct consequence of the sellar fracture itself and is usually considered to be the result of associated cerebral trauma. This case prompted us to screen the literature on sellar fracture to gain a better understanding of the mechanism of death.

Cosine Lobe Based Relighting from Gradient Illumination Photographs

We present an image-based method for relighting a scene by analytically fitting cosine lobes to the reflectance function at each pixel, based on gradient illumination photographs. Realistic relighting results for many materials are obtained using a single per-pixel cosine lobe obtained from just two color photographs: one under uniform white illumination and the other under colored gradient illumination. For materials with wavelength-dependent scattering, a better fit can be obtained using independent cosine lobes for the red, green, and blue channels, obtained from three achromatic gradient illumination conditions instead of the colored gradient condition. We explore two cosine lobe reflectance functions, both of which allow an analytic fit to the gradient conditions. One is non-zero over half the sphere of lighting directions, which works well for diffuse and specular materials, but fails for materials with broader scattering such as fur. The other is non-zero everywhere, which works well for broadly scattering materials and still produces visually plausible results for diffuse and specular materials. We also perform an approximate diffuse/specular separation of the reflectance, and estimate scene geometry from the recovered photometric normals to produce hard shadows cast by the geometry, while still reconstructing the input photographs exactly.

Differential association of MUC5AC and CLCA1 expression in small cartilaginous airways of RAO-affected and control horses

REASONS FOR PERFORMING STUDY: Airway mucus accumulation is associated with indoor irritant and allergen exposure in horses with recurrent airway obstruction (RAO). Epidermal growth factor receptor (EGFR) and a chloride channel (calcium activated, family member 1; CLCA1) are key signalling molecules involved in mucin gene expression. OBJECTIVES: We hypothesised that exposure to irritants and aeroallergens would lead to increased expression of the mucin gene eqMUC5AC and increased stored mucosubstance in the airways of RAO-affected horses, associated with increased neutrophils and CLCA1 and EGFR mRNA levels. METHODS: We performed quantitative RT-PCR of eqMUC5AC, CLCA1 and EGFR; volume density measurements of intraepithelial mucosubstances; and cytological differentiation of intraluminal inflammatory cells in small cartilaginous airways from cranial left and right and caudal left and right lung lobes of 5 clinically healthy and 5 RAO-affected horses that had been exposed to indoor stable environment for 5 days before euthanasia. RESULTS: Neutrophils were increased in RAO-affected horses compared to clinically healthy controls. EqMUC5AC mRNA levels were positively correlated with both CLCA1 and EGFR mRNA levels in RAO-affected horses but only with CLCA1 in controls. The relationship between eqMUC5AC and CLCA1 differed in the 2 groups of horses with RAO-affected animals overexpressing CLCA1 in relation to eqMUC5AC. CONCLUSIONS: These data implicate CLCA1 as a signalling molecule in the expression of eqMUC5AC in horses but also suggest differential regulation by CLCA1 and EGFR between horses with RAO and those with milder degrees of airway inflammation.

Adult Neurogenesis in Drosophila

Adult neurogenesis has been linked to several cognitive functions and neurological disorders. Description of adult neurogenesis in a model organism like Drosophila could facilitate the genetic study of normal and abnormal neurogenesis in the adult brain. So far, formation of new neurons has not been detected in adult fly brains and hence has been thought to be absent in Drosophila. Here, we used an improved lineage-labeling method to show that, surprisingly, adult neurogenesis occurs in the medulla cortex of the Drosophila optic lobes. We also find that acute brain damage to this region stimulates adult neurogenesis. Finally, we identify a factor induced by acute damage, which is sufficient to specifically activate the proliferation of a cell type with adult neuroblast characteristics. Our results reveal unexpected plasticity in the adult Drosophila brain and describe a unique model for the genetic analysis of adult neurogenesis, plasticity, and brain regeneration.

Denudation rates of small transient catchments controlled by former glaciation: The Hörnli nunatak in the northeastern Swiss Alpine Foreland

Extensive glaciers repeatedly occupied the northern Alpine Foreland during the Pleistocene and left a strongly glacially overprinted low slope landscape. Only few islands appeared as nunataks standing above the surface of the large piedmont glacier lobes. These nunatak areas kept their original shape, manifested in steep catchments with mean slopes up to 33 . Even though not glaciated, these catchments where significantly affected by base-level changes occurring as a consequence of phases of glacier advances and retreats. Both domains, the glacially eroded and non-eroded, are therefore prone to different mechanisms and time-scales of fluvial and colluvial re-adjustment. In this study we investigate these effects by exploring the spatial distribution and magnitude of denudation in the Hörnli region of the eastern Swiss Alpine Foreland in the present Interglacial. The area represents both domains in a relatively small area with largely uniform tectonic, lithologic and climatic conditions. The differences in Holocene andscape evolution are investigated using topographic analyses and catchment-averaged denudation rates derived from 10Be concentrations in fluvial quartz sand. We find that in formerly non-glaciated, fluvially dominated catchments close hillslope-channel coupling prevails and that these catchments yield high average denudation rates of 350 mm/ka. Glacially overprinted catchments yielded catchment-wide denudation rates an order of magnitude lower. These low denudation rates are hypothesized to be the consequence of both (i) a dominance of slow hillslope processes and (ii) admixture of high concentration, pre-LGM glacial sediment. This suggests that a) a careful field investigation must accompany the denudation rate studies and b) that the concept of area-weighted cosmogenic nuclide denudation rates must be considered in light of the predominant catchment processes.

Ataxia due to vertebral hemangiosarcoma with evidence of disseminated disease in a 20-year old Swiss Warmblood mare

A 20-year old Swiss Warmblood mare was referred to the Swiss Institute of Equine Medicine with a history of poor performance, coughing and ataxia and hindlimb weakness which progressed to recumbency. Lung auscultation revealed pronounced wheezing, blood work showed signs of chronic inflammation and increased bone turnover and thoracic ultrasound indicated patchy pulmonary consolidation. Cerebrospinal fluid revealed only mild, unspecific changes allowing exclusion of meningoencephalomyelitis and clinically relevant bleeding. Despite medical treatment and support in a sling the mare did not improve and was euthanized. Necropsy revealed a poorly demarcated, non-encapsulated and invasively growing mass dorsally in the musculature at the level of the forth cervical vertebra (C4) infiltrating the vertebral body and the spinal canal at the level of C1–C2. Multiple nodular, firm masses were present in all lobes of the lung and appeared to be mainly located in vessels. Histologically the masses were composed of spindle cells with marked anisocytosis, anisocaryosis, a high mitotic activity and showed invasive growth. These neoplastic cells stained positive for CD31, an endothelial cell marker, which confirmed diagnosis of a hemangiosarcoma. Definite ante mortem diagnosis of hemangiosarcoma, which is rare in horses, is challenging. Besides the vertebral localization, disseminated, locally invasive and cutaneous forms of hemangiosarcoma exist and can be either acquired or congenital. Prognosis for equine hemangiosarcoma and response to treatment are usually poor and progression of clinical signs is rapid. Vertebral hemangiosarcoma is an uncommon cause of spinal ataxia in horses.

Lobe specific Ca2+-calmodulin nano-domain in neuronal spines: a single molecule level analysis.

Calmodulin (CaM) is a ubiquitous Ca(2+) buffer and second messenger that affects cellular function as diverse as cardiac excitability, synaptic plasticity, and gene transcription. In CA1 pyramidal neurons, CaM regulates two opposing Ca(2+)-dependent processes that underlie memory formation: long-term potentiation (LTP) and long-term depression (LTD). Induction of LTP and LTD require activation of Ca(2+)-CaM-dependent enzymes: Ca(2+)/CaM-dependent kinase II (CaMKII) and calcineurin, respectively. Yet, it remains unclear as to how Ca(2+) and CaM produce these two opposing effects, LTP and LTD. CaM binds 4 Ca(2+) ions: two in its N-terminal lobe and two in its C-terminal lobe. Experimental studies have shown that the N- and C-terminal lobes of CaM have different binding kinetics toward Ca(2+) and its downstream targets. This may suggest that each lobe of CaM differentially responds to Ca(2+) signal patterns. Here, we use a novel event-driven particle-based Monte Carlo simulation and statistical point pattern analysis to explore the spatial and temporal dynamics of lobe-specific Ca(2+)-CaM interaction at the single molecule level. We show that the N-lobe of CaM, but not the C-lobe, exhibits a nano-scale domain of activation that is highly sensitive to the location of Ca(2+) channels, and to the microscopic injection rate of Ca(2+) ions. We also demonstrate that Ca(2+) saturation takes place via two different pathways depending on the Ca(2+) injection rate, one dominated by the N-terminal lobe, and the other one by the C-terminal lobe. Taken together, these results suggest that the two lobes of CaM function as distinct Ca(2+) sensors that can differentially transduce Ca(2+) influx to downstream targets. We discuss a possible role of the N-terminal lobe-specific Ca(2+)-CaM nano-domain in CaMKII activation required for the induction of synaptic plasticity.

Strong-meter and weak-meter rhythm identification in spina bifida meningomyelocele and volumetric parcellation of rhythm-relevant cerebellar regions.

Children with spina bifida meningomyelocele (SBM) are impaired relative to controls in terms of discriminating strong-meter and weak-meter rhythms, so congenital cerebellar dysmorphologies that affect rhythmic movements also disrupt rhythm perception. Cerebellar parcellations in children with SBM showed an abnormal configuration of volume fractions in cerebellar regions important for rhythm function: a smaller inferior-posterior lobe, and larger anterior and superior-posterior lobes.