Limited number of immunoglobulin VH regions expressed in the mutant rabbit “Alicia”

A unique feature of rabbit Ig is the presence of V_H region allotypic specificities. In normal rabbits, more than 80% of circulating immunoglobulin molecules bear theV_Ha allotypic specificities, a1, a2 or a3; the remaining 10% to 20% of immunoglobulin molecules lack V_Ha allotypic specificities and are designated V_Ha^?. A mutant rabbit designated Alicia, in contrast, has predominantly serumimmunoglobulin molecules that lack the V_Ha allotypic specificities (Kelus and Weiss, Proc. Natl. Acad. Sci. USA 1986. 83: 4883). To study the nature and molecular complexity of V_Ha^? molecules, we cloned and determined the nucleotide sequence of seven cDNA prepared from splenic RNA of an Alicia rabbit. Six ofthe clones appeared to encode V_Ha^? molecules; the framework regions encoded by these clones were remarkably similar to each other, each having an unusual insertion of four amino acids at position 10. This insertion of four amino acids has beenseen in only 2 of 54 sequenced rabbit V_H genes. The similarity of the sequences of the six V_Ha^? clones to each other and their dissimilarity to most other V_H genes leads us to suggest that the V_Ha^? molecules in Alicia rabbits are derived predominantly from one or a small number of very similar V_H genes. Such preferential utilization of a small number of V_H genes may explain the allelic inheritance of V_H allotypes.     

Top‐down and bottom‐up influences on the left ventral occipito‐temporal cortex during visual word recognition: An analysis of effective connectivity

The functional role of the left ventral occipito‐temporal cortex (vOT) in visual word processing has been studied extensively. A prominent observation is higher activation for unfamiliar but pronounceable letter strings compared to regular words in this region. Some functional accounts have interpreted this finding as driven by top‐down influences (e.g., Dehaene and Cohen [ 2011 ]: Trends Cogn Sci 15:254–262; Price and Devlin [ 2011 ]: Trends Cogn Sci 15:246–253), while others have suggested a difference in bottom‐up processing (e.g., Glezer et al. [ 2009 ]: Neuron 62:199–204; Kronbichler et al. [ 2007 ]: J Cogn Neurosci 19:1584–1594). We used dynamic causal modeling for fMRI data to test bottom‐up and top‐down influences on the left vOT during visual processing of regular words and unfamiliar letter strings. Regular words (e.g., taxi) and unfamiliar letter strings of pseudohomophones (e.g., taksi) were presented in the context of a phonological lexical decision task (i.e., “Does the item sound like a word?”). We found no differences in top‐down signaling, but a strong increase in bottom‐up signaling from the occipital cortex to the left vOT for pseudohomophones compared to words. This finding can be linked to functional accounts which assume that the left vOT contains neurons tuned to complex orthographic features such as morphemes or words [e.g., Dehaene and Cohen [ 2011 ]: Trends Cogn Sci 15:254‐262; Kronbichler et al. [ 2007 ]: J Cogn Neurosci 19:1584–1594]: For words, bottom‐up signals converge onto a matching orthographic representation in the left vOT. For pseudohomophones, the propagated signals do not converge, but (partially) activate multiple orthographic word representations, reflected in increased effective connectivity. Hum Brain Mapp 35:1668–1680, 2014. © 2013 Wiley Periodicals, Inc.     

Influence of residual alveolar bone height on implant stability in the maxilla: an experimental animal study

Aims/Background: Empirically, for implant placement associated with sinus floor augmentation, a minimum of five mm of residual crestal bone height has been recommended in order to achieve sufficient initial implant stability. It has been the aim of the study to test this assumption in an experimental animal trial. Material and methods: In eight mini pigs, three premolars and two molars were removed on one side of the maxilla. Three months later the animals were assigned to four groups of two animals each. A cavity was created at the base of the alveolar process so that the residual bone height was reduced to 2, 4, 6 and 8 mm, respectively. The coronal part of the alveolar crest remained unchanged. An inlay augmentation procedure was carried out using a particulated autogenous bone graft from the iliac crest, and six implants (Xive, diameter 3.8 mm, length 13 mm) were placed. Implant stability was assessed by resonance frequency analysis at the time of implant placement (T0), after 6 months of unloaded healing (T1) and after 6 months of functional loading (T2). Results: During follow‐up, two implants were lost in sites with a residual alveolar bone height of 2 mm. At the time of implant placement, resonance frequencies were 6754.4±268, 6500.3±281.5, 6890.3±255.4 and 7877.9±233.7 Hz for residual bone heights of 2, 4, 6 and 8 mm, respectively. At stage‐two surgery and after 6 months of functional loading, resonance frequencies were 6431.7±290.8, 6351.8±437.6, 6213.4±376.2 and 6826.8±458.9 Hz vs. 6171±437.4, 6047±572.4, 6156.7±272.6 and 6412.8±283.5 Hz. Statistical analysis revealed an association of residual alveolar height and implant stability at T0 and T1 only (P<0.01), while bone height was not found to influence implant survival. Conclusion: The results of the present trial demonstrate an association of alveolar bone height and implant stability at the time of implant placement and stage‐two surgery. Yet the assumption that 5 mm of residual crestal bone height is a relevant threshold for simultaneous implant placement and sinus floor augmentation is not supported from an experimental point of view.     

Hepatic encephalopathy influences high-affinity uptake of transmitter glutamate and aspartate into the hippocampal formation

The present work was carried out to study the influence of ammonia and factors from sera and cerebrospinal fluid (CSF) from patients with different degrees of chronic liver diseases on [³H]D-aspartate (Asp) and [³H]L-glutamate (Glu) high-affinity uptake into the rat hippocampal formation. For comparison, high-affinity uptake of Glu and Asp was determined in human hippocampal brain tissue obtained at autopsy from cirrhotic patients dying in hepatic coma and from control brains free from neurological, psychiatric, or hepatic diseases. Sera and CSF from patients with chronic liver failure and hepatic encephalopathy (HE) were seen to reduce dramatically Glu and Asp uptake into rat hippocampal dendritic layers. A close inverse relationship was found to exist between the level of ammonia in the sera and the inhibition of uptake, both phenomena correlating highly with the extent of liver failure. The present findings, obtained after dilution of sera from patients with HE while maintaining initial ammonium levels, elucidate, however, that ammonia alone cannot account for the reduction in Glu/Asp uptake capacity. The inhibition of Asp uptake into human hippocampal formation of patients dying in hepatic coma was even more pronounced when compared to that found in rat hippocampus incubated in sera and CSF from patients. Glu/Asp uptake into brain tissue is supposed to be an important factor in the pathogenesis of HE accompanying liver dysfunctions.     

Cardiac chamber quantification using magnetic resonance imaging at 7 Tesla—a pilot study

Objectives  

Interest in cardiovascular magnetic resonance (CMR) at 7 T is motivated by the expected increase in spatial and temporal resolution, but the method is technically challenging. We examined the feasibility of cardiac chamber quantification at 7 T.     

Safety and efficacy of eculizumab for the prevention of antibody‐mediated rejection after deceased‐donor kidney transplantation in patients with preformed donor‐specific antibodies

The presence of preformed donor‐specific antibodies in transplant recipients increases the risk of acute antibody‐mediated rejection (AMR). Results of an open‐label single‐arm trial to evaluate the safety and efficacy of eculizumab in preventing acute AMR in recipients of deceased‐donor kidney transplants with preformed donor‐specific antibodies are reported. Participants received eculizumab as follows: 1200 mg immediately before reperfusion; 900 mg on posttransplant days 1, 7, 14, 21, and 28; and 1200 mg at weeks 5, 7, and 9. All patients received thymoglobulin induction therapy and standard maintenance immunosuppression including steroids. The primary end point was treatment failure rate, a composite of biopsy‐proved grade II/III AMR (Banff 2007 criteria), graft loss, death, or loss to follow‐up, within 9 weeks posttransplant. Eighty patients received transplants (48 women); the median age was 52 years (range 24‐70 years). Observed treatment failure rate (8.8%) was significantly lower than expected for standard care (40%; P < .001). By 9 weeks, 3 of 80 patients had experienced AMR, and 4 of 80 had experienced graft loss. At 36 months, graft and patient survival rates were 83.4% and 91.5%, respectively. Eculizumab was well tolerated and no new safety concerns were identified. Eculizumab has the potential to provide prophylaxis against injury caused by acute AMR in such patients (EudraCT 2010‐019631‐35).     

Is bone-cement augmentation of screw-anchor fixation systems superior in unstable femoral neck fractures? A biomechanical cadaveric study

Objectives

Improved fixation techniques with optional use of bone cements for implant augmentation have been developed to enhance stability and reduce complication rates after osteosynthesis of femoral neck fractures. This biomechanical study aimed to evaluate the effect of cement augmentation on implant anchorage and overall performance of screw-anchor fixation systems in unstable femoral neck fractures.

Surgical management of intracranial subependymomas

Background  

Intracranial subependymomas are rare, slow-growing and usually non-invasive tumors. The aim of this study was to analyze our experience with the surgical treatment of intracranial subependymomas.     

Long-term result after femoral head substitution in postinfectious aplasia of the femoral head

Purpose  

This case report presents a new and unique surgical greater trochanter split procedure for reconstructing a hip joint after an infantile hip sepsis with consequent aplasia of the femoral head.