Aversive Conditioning of Spatial Position Sharpens Neural Population-Level Tuning in Visual Cortex and Selectively Alters Alpha-Band Activity.

Processing capabilities for many low-level visual features are experientially malleable, aiding sighted organisms in adapting to dynamic environments. Explicit instructions to attend a specific visual field location influence retinotopic visuocortical activity, amplifying responses to stimuli appearing at cued spatial positions. It remains undetermined both how such prioritization affects surrounding nonprioritized locations, and if a given retinotopic spatial position can attain enhanced cortical representation through experience rather than instruction. The current report examined visuocortical response changes as human observers (N = 51, 19 male) learned, through differential classical conditioning, to associate specific screen locations with aversive outcomes. Using dense-array EEG and pupillometry, we tested the preregistered hypotheses of either sharpening or generalization around an aversively associated location following a single conditioning session. Competing hypotheses tested whether mean response changes would take the form of a Gaussian (generalization) or difference-of-Gaussian (sharpening) distribution over spatial positions, peaking at the viewing location paired with a noxious noise. Occipital 15 Hz steady-state visual evoked potential responses were selectively heightened when viewing aversively paired locations and displayed a nonlinear, difference-of-Gaussian profile across neighboring locations, consistent with suppressive surround modulation of nonprioritized positions. Measures of alpha-band (8-12 Hz) activity were differentially altered in anterior versus posterior locations, while pupil diameter exhibited selectively heightened responses to noise-paired locations but did not evince differences across the nonpaired locations. These results indicate that visuocortical spatial representations are sharpened in response to location-specific aversive conditioning, while top-down influences indexed by alpha-power reduction exhibit posterior generalization and anterior sharpening.SIGNIFICANCE STATEMENT It is increasingly recognized that early visual cortex is not a static processor of physical features, but is instead constantly shaped by perceptual experience. It remains unclear, however, to what extent the cortical representation of many fundamental features, including visual field location, is malleable by experience. Using EEG and an aversive classical conditioning paradigm, we observed sharpening of visuocortical responses to stimuli appearing at aversively associated locations along with location-selective facilitation of response systems indexed by pupil diameter and EEG alpha power. These findings highlight the experience-dependent flexibility of retinotopic spatial representations in visual cortex, opening avenues toward novel treatment targets in disorders of attention and spatial cognition.

Effects of affective content and motivational context on neural gain functions during naturalistic scene perception.

Visual scene processing is modulated by semantic, motivational, and emotional factors, in addition to physical scene statistics. An open question is to what extent those factors affect low-level visual processing. One index of low-level visual processing is the contrast response function (CRF), representing the change in neural or psychophysical gain with increasing stimulus contrast. Here we aimed to (a) establish the use of an electrophysiological technique for assessing CRFs with complex emotional scenes and (b) examine the effects of motivational context and emotional content on CRFs elicited by naturalistic stimuli, including faces and complex scenes (humans, animals). Motivational context varied by expectancy of threat (a noxious noise) versus safety. CRFs were measured in 18 participants by means of sweep steady-state visual evoked potentials. Results showed a facilitation in visuocortical sensitivity (contrast gain) under threat, compared with safe conditions, across all stimulus categories. Facial stimuli prompted heightened neural response gain, compared with scenes. Within the scenes, response gain was smaller for scenes high in emotional arousal, compared with low-arousing scenes, consistent with interference effects of emotional content. These findings support the notion that motivational context alters the contrast sensitivity of cortical tissue, differing from changes in response gain (activation) when visual cues themselves carry motivational/affective relevance.

Effects of Experience on Spatial Frequency Tuning in the Visual System: Behavioral, Visuocortical, and Alpha-band Responses.

Using electrophysiology and a classic fear conditioning paradigm, this work examined adaptive visuocortical changes in spatial frequency tuning in a sample of 50 undergraduate students. High-density EEG was recorded while participants viewed 400 total trials of individually presented Gabor patches of 10 different spatial frequencies. Patches were flickered to produce sweep steady-state visual evoked potentials (ssVEPs) at a temporal frequency of 13.33 Hz, with stimulus contrast ramping up from 0% to 41% Michelson over the course of each 2800-msec trial. During the final 200 trials, a selected range of Gabor stimuli (either the lowest or highest spatial frequencies, manipulated between participants) were paired with an aversive 90-dB white noise auditory stimulus. Changes in spatial frequency tuning from before to after conditioning for paired and unpaired gratings were evaluated at the behavioral and electrophysiological level. Specifically, ssVEP amplitude changes were evaluated for lateral inhibition and generalization trends, whereas change in alpha band (8-12 Hz) activity was tested for a generalization trend across spatial frequencies, using permutation-controlled F contrasts. Overall time courses of the sweep ssVEP amplitude envelope and alpha-band power were orthogonal, and ssVEPs proved insensitive to spatial frequency conditioning. Alpha reduction (blocking) was most pronounced when viewing fear-conditioned spatial frequencies, with blocking decreasing along the gradient of spatial frequencies preceding conditioned frequencies, indicating generalization across spatial frequencies. Results suggest that alpha power reduction-conceptually linked to engagement of attention and alertness/arousal mechanisms-to fear-conditioned stimuli operates independently of low-level spatial frequency processing (indexed by ssVEPs) in primary visual cortex.

Impact of joint status on contraction steadiness of m. quadriceps femoris in people with severe haemophilia.

Impaired contraction steadiness of lower limb muscles affects functional performance and may increase injury risk. We hypothesize that haemophilic arthropathy of the knee and the strength status of quadriceps are relevant factors which compromise a steady contraction. This study addresses the questions if impaired steadiness of the quadriceps is verifiable in people with haemophilia (PWH) and whether a connection between the status of the knee joint and quadriceps strength exists. A total of 157 PWH and 85 controls (C) performed a strength test with a knee extensor device to evaluate their bilateral and unilateral maximal quadriceps strength and steadiness. Isometric steadiness was measured by the coefficient of variation of maximum peak torque (CV-MVIC in %). For classification of the knee joint status the World Federation of Haemophilia (WFH) score was used. Lower steadiness (higher CV values) was found in PWH compared with C during bilateral [PWH vs. C; 0.63 (0.36/1.13) vs. 0.35 (0.15/0.72), median (Q25/Q75) P < 0.001] and unilateral trials [left leg: 0.70 (0.32/1.64) vs. 0.50 (0.23/1.04), P < 0.05; right leg: 0.68 (0.29/1.51) vs. 0.39 (0.18/0.68), P < 0.001]. PWH with a WFH score difference (≥1) between their extremities showed a less steady contraction in the more affected extremity (P < 0.05). More unsteady contractions have also been found in extremities with lower quadriceps strength compared with the contralateral stronger extremities (P < 0.001), whereby the weaker extremities were associated with a worse joint status (P < 0.001). The results of this study verify an impaired ability to realize a steady contraction of quadriceps in PWH and the influence of joint damage and strength on its manifestation.

Reciprocal effects of Interferon-γ and IL-4 on differentiation to osteoclast-like cells by RANKL or LPS.

OBJECTIVE: LPS can induce differentiation to osteoclast-like cells independent of RANKL. In comparison with RANKL, the effects of Th1 and Th2 cytokines on LPS-induced osteoclastogenesis have not been extensively studied. In this study, we investigated the effects of IFN-γ and IL-4 on RANKL- or LPS-induced osteoclastogenesis. MATERIALS AND METHODS: RAW 264.7 cells were induced to differentiate into osteoclast-like cells by RANKL or LPS, in the absence or presence of IFN-γ or IL-4. The number of TRAP-positive, multinucleated (≥ 3 nuclei) cells (MNCs) was counted. mRNA and protein levels of TRAP and cathepsin K were determined by quantitative RT-PCR and Western immunoblot, respectively. Expression of other genes implicated in osteoclast and macrophage differentiation and inflammation was also quantitated and was subsequently assessed in bone marrow-derived macrophages (BMMs). Phagocytic capacity of differentiated RAW264.7 was investigated by the uptake of pHrodo S. aureus bioparticles conjugates. RESULTS: In contrast to the RANKL-treated cell population that gained more macrophage-like properties at the level of gene and protein expression as well as phagocytosis in the presence of IFN-γ or IL-4, the LPS-induced population gained more osteoclast-like properties by the addition of the same factors. CONCLUSION: These data suggest that the adaptive immune system, through either Th1 or Th2 cytokines, is able to modify the differentiation process of osteoclasts in inflammatory situations. Moreover, the study provides an example of different regulation of osteoclast differentiation during physiological and inflammatory conditions.

Measurement of the neutron electric to magnetic form factor ratio at Q2=1.58 GeV2 using the reaction 3He[over →](e[over →],e'n)pp.

A measurement of beam helicity asymmetries in the reaction 3He[over →](e[over →],e'n)pp is performed at the Mainz Microtron in quasielastic kinematics to determine the electric to magnetic form factor ratio of the neutron GEn/GMn at a four-momentum transfer Q2=1.58 GeV2. Longitudinally polarized electrons are scattered on a highly polarized 3He gas target. The scattered electrons are detected with a high-resolution magnetic spectrometer, and the ejected neutrons are detected with a dedicated neutron detector composed of scintillator bars. To reduce systematic errors, data are taken for four different target polarization orientations allowing the determination of GEn/GMn from a double ratio. We find µnGEn/GMn=0.250±0.058(stat)±0.017(syst).

Quadriceps strength, inter-extremity difference (IED) and joint status in adult persons with severe haemophilia in different age stages.

Quadriceps weakness seems to be a hallmark in adult persons with severe haemophilia (PWH). The purpose of this study was to compare PWH and non-haemophilic controls in different age stages with reference to joint status and quadriceps strength. Further aims were to examine the extent of strength-specific inter-extremity-difference (IED) and the prevalence of abnormal IED (AIED). A total of 106 adults with severe haemophilia (H) and 80 controls (C) had undergone an orthopaedic examination for classification of knee and ankle status using the WFH score. Quadriceps strength was evaluated unilaterally as well as bilaterally with a knee extensor device. Each group was divided into four age-related subgroups (HA/CA: 18-29, HB/CB: 30-39, HC/CC: 40-49, HD/CD: 50-70; in years). H presented a worse knee and ankle status than C indicated by higher WFH scores (P < 0.01). Regarding the age-matched subgroups only HB showed higher knee scores than CB (P < 0.05). The ankles were clinically more affected in HB-HD compared with those in age-matched controls (P < 0.05). H showed lower quadriceps strength than C (P < 0.05). In addition, all subgroups of H presented lower strength (HA: 10-17, HB: 19-23, HC: 35-36, HD: 53-61; in%, P < 0.05). IED was higher in H than in C [H: 12.0 (5.3/32.2) vs. C: 7.1 (2.9/10.9); Median (quartiles) in%, P < 0.001] and increased with age in H. We discovered an AIED in 35% of H. These findings highlight the importance for the early implementation of preventive and rehabilitative muscle training programmes in the comprehensive treatment of PWH.

[Analysis of muscle function with kinetic superficial EMG in children with haemophilia - recognizing subclinical changes, establishing individual therapy, quality control]. / Muskelfunktionsmessung mit kinetischem Oberflächen-EMG bei Kindern mit Hämophilie. Erkennung subklinischer Veränderungen, Etablierung individueller Therapie, Qualitätskontrolle.

UNLABELLED: Electromyography (EMG) measures muscle electricity. It depends on muscle contraction and central motor control. Muscles react very sensitive on external signals (e. g. bleeding), The resulting changes can be shown in EMG. PATIENTS, METHODS: A first study included 51 children and young adults from Costa Rica. They underwent a clinical examination and EMG of the hip, knee and ankle joints. Resting muscle tone, maximal isometric contraction and three typical isotonic movements of the joints were measured. First step of analysis was to characterize typical pathogenic changes in the muscles and to find a corresponding physical therapy to minimize these changes. RESULTS: It showed that EMG is a good marker for muscle condition. It helps to individualize therapy and improve effectivity of physical and physiotherapeutic treatment of the locomotive system of children and young adults with hemophilia. It can help to recognize early subclinical changes and to control the outcome of therapeutic modalities.

TGF-beta/extracellular matrix interactions in dentin matrix: a role in regulating sequestration and protection of bioactivity.

TGF-beta isoforms sequestrated in dentin matrix potentially provide a reservoir of bioactive molecules that may influence cell behavior in the dentin-pulp complex following tissue injury. The association of these growth factors with dentin matrix and the influence of such associations on the bioactivity of growth factors are still unclear. We used surface plasmon resonance technology in the BIAcore 3000 system to investigate the binding of TGF-beta isoforms 1 and 3 to purified decorin, biglycan, and EDTA soluble dentin matrix components. TGF-beta isoforms 1 and 3 were immobilized on sensorchips CM4 through amine coupling. For kinetic studies of protein binding, purified decorin and biglycan, isolated EDTA soluble dentin matrix, and dentin matrix immunodepleted of decorin and/or biglycan were injected over TGF-beta isoforms and allowed to interact. Programmed kinetic analysis software provided sensorgrams for each concentration of proteoglycan or dentin matrix extract injected. Purified decorin and biglycan and dentin matrix extract bound to the TGF-beta isoforms. However, the association with TGF-beta3 was much weaker than that with TGF-beta1. After immunoaffinity depletion of the dentin matrix extract, the level of interaction between the dentin matrix extract and TGF-beta was significantly reduced. These results suggest isoform-specific interactions between decorin/biglycan and TGF-beta isoforms 1 and 3, which may explain why TGF-beta3 is not detected in the dentin matrix despite being expressed at higher levels than TGF-beta1 in odontoblasts. These proteoglycans appear to play a significant role in TGF-beta/extracellular matrix interactions and may be important in the sequestration of these growth factors in the dentin matrix.

Bone matrix proteins: isolation and characterization of a novel cell-binding keratan sulfate proteoglycan (osteoadherin) from bovine bone.

A small cell-binding proteoglycan for which we propose the name osteoadherin was extracted from bovine bone with guanidine hydrochloride-containing EDTA. It was purified to homogeneity using a combination of ion-exchange chromatography, hydroxyapatite chromatography, and gel filtration. The Mof the proteoglycan was 85, 000 as determined by SDS-PAGE. The protein is rich in aspartic acid, glutamic acid, and leucine. Two internal octapeptides from the proteoglycan contained the sequences Glu-Ile-Asn-Leu-Ser-His-Asn-Lys and Arg-Asp-Leu-Tyr-Phe-Asn-Lys-Ile. These sequences are not previously described, and support the notion that osteoadherin belongs to the family of leucine-rich repeat proteins. A monospecific antiserum was raised in rabbits. An enzyme-linked immunosorbent assay was developed, and showed the osteoadherin content of bone extracts to be 0.4 mg/g of tissue wet weight, whereas none was found in extracts of various other bovine tissues. Metabolic labeling of primary bovine osteoblasts followed by immunoprecipitation showed the cells to synthesize and secrete the proteoglycan. Digesting the immunoprecipitated osteoadherin with N-glycosidase reduced its apparent size to 47 kD, thus showing the presence of several N-linked oligosaccharides. Digestion with keratanase indicated some of the oligosaccharides to be extended to keratan sulfate chains. In immunohistochemical studies of the bovine fetal rib growth plate, osteoadherin was exclusively identified in the primary bone spongiosa. Osteoadherin binds to hydroxyapatite. A potential function of this proteoglycan is to bind cells, since we showed it to be as efficient as fibronectin in promoting osteoblast attachment in vitro. The binding appears to be mediated by the integrin alphavbeta3, since this was the only integrin isolated by osteoadherin affinity chromatography of surface-iodinated osteoblast extracts.

[Pathomechanisms of organ failure. Mitochondrial dysfunction in sepsis]. / Pathomechanismen des Organversagens. Zelluläre Sauerstoffverwertungsstörung im Rahmen der Sepsis.

Proinflammatory mediators as well as increased formation of reactive oxygen and nitrogen species impair cellular respiration during sepsis. In particular, the highly reactive peroxynitrite irreversibly damages lipids, proteins and nucleic acids and also inhibits enzyme complexes of the respiratory chain. In this way cellular metabolic functions and subsequently organ functions are also impaired. Repair of DNA by poly(ADP-ribose)polymerase consumes large amounts of nicotinamide adenine dinucleotide (NAD+) which leads to cellular NAD+ depletion further promoting inflammation. This article summarizes central aspects of the pathophysiology of mitochondrial dysfunction during sepsis and gives an overview about newly developed strategies which proved effective in experimental studies and may have a potential clinical application in the future.

Evaluation of lower anterior dental changes in patients treated with self-ligating brackets.

The aim of this study was to evaluate and compare changes in linear distance and inclination of lower incisors and canines and intercanine distance after a 30 months orthodontic treatment with self-ligating appliances. Seven patients were treated orthodontically with a Roth prescription passive self-ligating bracket. To perform the measurements and comparisons, CBCT scans were taken before the start of the orthodontic treatment (T1) and after a period of 30 months treatment (T2). The following measurements were performed: (1) the lower incisors and canines inclination in relation to the mandibular plane, (2) intercanine linear distance in millimeters and (3) linear distance in millimeters of the incisal and apical part of lower anterior teeth to a plane (POGM) passing through pogonion point and perpendicular to the mandibular plane. No significant difference were observed between T1 and T2 for canine inclination (p = 0.835), incisors inclination (p = 0.149), canine incisal distance to POGM (p = 0.423) and incisors incisal distance to POGM (p = 0.966), however canine apical distance (p = 0.049) and incisors apical distance (p = 0.002) to POGM was lower at T1 than at T2. The intercanine distance was significantly lower (p = 0.022) at T1 when compared to T2. The use of passive self-ligating brackets in orthodontic treatment to solve 4 mm tooth crowding were able to produce dental arch expansion by bodily tooth movement.

Nucleobindin 1 (NUCB1) is a Golgi-resident marker of neurons.

Nucleobindin 1 (NUCB1; also known as CALNUC or NUC) is a putative DNA- and calcium-binding protein and exhibits significant structural homology with the protein nucleobindin 2 (NUCB2; also known as nesfatin). While NUCB2 has been mapped in detail in the brain and implicated in the hypothalamic control of energy metabolism, no study has to date addressed the presence of NUCB1 in the central nervous system. Here we have explored the expression and distribution of NUCB1 in the rat brain and spinal cord, using RT-PCR, immunofluorescence and in situ hybridization. NUCB1 mRNA and protein was found to be present in all brain regions, extending to the spinal cord and dorsal root ganglia. Double-staining for NUCB1 and NeuN, glial fibrillary acidic protein and myelin basic protein revealed that NUCB1 is exclusively found in neurons, and not in glial or ependymal cells. Notably, NUCB1-immunoreactivity was observed in all neurons examined, making no distinction between previously identified glutamatergic and GABAergic populations, including those that are known not to stain for NeuN. This included the markedly more restricted population of NUCB2-expressing neurons in the brain. The protein was detected in cell somata and proximal dendrites, but not in axons or terminal structures. Further examination of the subcellular distribution of NUCB1 using organelle-specific markers revealed its consistent presence in the Golgi apparatus. These findings identify NUCB1 as a novel pan-neuronal marker. Along with the recent demonstration of broad expression of the protein in endocrine cells, the present results suggest that NUCB1 may play a role in spatiotemporal calcium handling in signaling cells.

The hyalectan degrading ADAMTS-1 enzyme is expressed by osteoblasts and up-regulated at regions of new bone formation.

During bone formation, there are numerous pivotal changes in the interrelationships between osteoblasts and molecules of the extracellular matrix (ECM). Consequently, the mechanisms that underlie the temporal and spatial distribution of ECM molecules in bone are of considerable interest in understanding its formation. A subfamily of a disintegrin and metalloproteinase (ADAMs) has been identified, which contain thrombospondin-like motifs (ADAMTS), and can break down several ECM molecules. Using reversed transcribed PCR, we identified ADAMTS-1, -4 and -5 mRNA expression in cultures of rat osteoblasts treated with ascorbic acid, beta-glycerophosphate and dexamethasone, molecules known to drive osteoblast differentiation. Of these, ADAMTS-1 followed most closely the osteogenic marker osteocalcin during in vitro mineralisation. Consequently, we studied, in detail, protein expression of ADAMTS-1 during in vitro osteogenesis together with ADAMTS-1 immunohistochemistry staining of sections from 2- and 10-day-old rat femur. Western analysis of osteoblast proteins showed ADAMTS-1 products that correspond well with both full-length and furin-processed species. In the ECM laid down by osteoblasts, only the mature secreted protein (approximately 90 kDa) and its accumulation during the later stages of osteogenesis in vitro were noticed. Furthermore, immunostaining with an antibody recognising ADAMTS-1 demonstrated strong expression around mineralised nodules and intense focal staining of putative new areas of nodule formation in vitro. Finally, immunohistochemistry of 2- and 10-day-old rat femur localised ADAMTS-1 protein to regions associated with osteogenesis. These data show that ADAMTS-1 protein accumulates in osteoblast ECM during differentiation. Furthermore, the focalised expression of ADAMTS-1 in regions of osteogenesis, both in vitro and in vivo, implicates this multifunctional protein to be involved in mineralised nodule and bone formation.

Amelotin--a Novel Secreted, Ameloblast-specific Protein.

We aimed to analyze the differential gene expression in various murine dental tissues, expecting to find novel factors that are involved in tooth formation. We here describe the identification of a novel ameloblast-specific gene, amelotin (AMTN), by differential display polymerase chain-reaction (DD-PCR) analysis of microdissected ameloblasts, odontoblasts, dental pulp, and alveolar bone cells of 10-day-old mouse incisors. The conceptually translated protein sequence was unique and showed significant homology only with its human orthologue. The amelotin genes from mouse and human displayed a similar exon-intron structure and were expressed from loci on chromosomes 5 and 4, respectively, which have been associated with various forms of amelogenesis imperfecta. Expression of amelotin mRNA was restricted to maturation-stage ameloblasts in developing murine molars and incisors. Amelotin protein was efficiently secreted from transfected cells in culture. Taken together, our findings suggest that amelotin is a novel factor produced by ameloblasts that plays a critical role in the formation of dental enamel.

Mouse models for extracellular matrix diseases.

Mutations of a number of genes encoding for extracellular matrix (ECM) proteins in mice have provided new insights regarding their role during development and disease. Many mouse strains have helped to verify the link between mutation and disease in humans, and others have produced unexpected phenotypes and identified new functions for ECM proteins. Finally, some null mutations in ECM genes provide no phenotypic alterations in mice, confronting the scientific community with a new challenge to search for their functions. This review lists all mouse strains with spontaneous and experimentally induced mutations in ECM genes. The phenotypes of these mice are discussed in comparison with the human diseases.

Distribution and synthesis of bone sialoprotein in metaphyseal bone of young rats show a distinctly different pattern from that of osteopontin.

Bone sialoprotein (BSP) and osteopontin (OPN) are two phosphorylated and highly glycosylated cell-binding proteins in bone. Both proteins bind to hydroxylapatite. The cell binding is mediated via an Arg-Gly-Asp (RGD) sequence and previous work indicates that both proteins can bind to the vitronectin receptor (alpha v beta 3). The present work shows that a prevailing localization of BSP in metaphyseal bone of the young rat is at the interface between calcified cartilage and bone. Thus BSP shows a conspicuous enrichment in the osteoid laid down by the invading osteoblasts immediately next to the calcified cartilage. Furthermore, the most prominent amount of BSP mRNA was detected in cells at the epiphyseal/metaphyseal border. As opposed to OPN, no prominent accumulation of BSP immunoreactivity was observed at bone surfaces that face cells. Also the synthesis OPN was most pronounced at sites very different from those of BSP. Thus, the most prominent amount of OPN mRNA was observed in cells close to the metaphyseal/diaphyseal border, where osteoclastic bone resorption is particularly active. Indeed, message was often found in cells surrounding osteoclasts without any detectable message. The distinctly different patterns of synthesis and expression of the two proteins indicate different roles in bone turnover at this stage of development. Thus, it appears that BSP has a specific role during the initial phases of bone formation at the cartilage/bone interface. On the other hand, the pattern of OPN synthesis and expression support and extend our previous data showing OPN particularly enriched at attachment sites of osteoclasts resorbing bone.

Radiation dose to the bladder wall from 2-[18F]fluoro-2-deoxy-D-glucose in adult humans.

Accurate determination of the radiation dose to the bladder wall from 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) is important because the bladder is the critical organ in radiotracer studies using 2-[18F]FDG. The radiation dose to the bladder wall from injected 2-[18F]FDG was estimated using both a dynamic bladder model and the conventional MIRD model. The dynamic model takes into account the excretion rate, the varying size of the bladder, the volume at injection, and an estimated bladder time activity curve. Our data from 302 adult subjects in a five-year period indicate that when the bladder is large at the time of injection, the dose to the bladder is greatly reduced. The absorbed dose of the bladder based on the dynamic model for an initial volume of 450 ml is 0.16 +/- 0.06 rad/mCi, while that for an initial volume of 200 ml is calculated to be 0.37 +/- 0.18 rad/mCi. The MIRD model estimates an average value of 0.35 +/- 0.16 rad/mCi for the 302 cases.

Regenerative response to membranous and enchondral lyophilized allogeneic bone in rabbit skull defects.

The regenerative responses of inlays of lyophilized allogeneic bone of membranous (skull) and enchondral (tibia) origin were studied in an experimental cranioplasty model in rabbits. The lyophilized bone particles were also bioassayed for inductive bone production in an orthotopic critical size defect rat model. Three trephined calvarial defects were evaluated in each of 14 adult rabbits. The experimental materials were implanted into two of the defects and the third was left empty for control purposes. The implants disclosed no major structural divergences as assessed by scanning electron microscopy. Healing was evaluated by light microscopy and contact radiography after periods of four and 15 weeks. The lyophilized bone allografts of both embryonic origins displayed a similar fashion of bone regeneration, bone marrow reappearance, and volumetric density of trabecular bone substance and displayed no obvious differences between experimental groups or intervals. The two materials exhibited low osteoinductive potential.