A New Biological Approach To Vital Pulp Therapy

Molecular biology is providing opportunities to develop new strategies or agents for the treatment of a wide variety of diseases. The availability of large amounts of highly purified proteins produced by recombinant DNA techniques is an obvious example. Recent evidence has implicated proteins belonging to the bone morphogenetic protein (BMP) subgroup of the transforming growth factor beta supergene family in tooth formation and dentinogenesis. It has long been known that bone and dentin contain bone morphogenetic protein activity. Recently, recombinant human BMP-2, -4, and -7 (also known as OP-1 ) have been shown to induce reparative dentin formation in experimental models of large direct pulp exposures in permanent teeth. The manner in which these agents act appears unique. New reparative dentin replaces the stimulating agents applied directly to the partially amputated pulp. Hence, the new tissue forms contiguous with, largely superficial to, and not at the expense of the remaining vital pulp tissue. This suggests a therapeutic approach permitting the induction of a predetermined and controlled amount of reparative dentin. Additionally, OP-l has been associated with the formation of reparative dentin after application to a freshly cut but intact layer of dentin. These findings may provide future clinicians with additional options for the treatment of substantially damaged or diseased vital teeth.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66969/2/10.1177_10454411950060030401.pd

BMP-7 gene transfer to inflamed ferret dental pulps

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73343/1/j.1600-0722.2001.00150.x.pd

Transplantation of human pulpal and gingival fibroblasts attached to synthetic scaffolds

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72582/1/j.0909-8836.1999.eos107408.x.pd

Evaluation of bonded boron/epoxy doublers for commercial aircraft aluminum structures

An 18 month laboratory test and stress analysis program was conducted to evaluate bonded boron/epoxy doublers for repairing cracks on aluminum aircraft structures. The objective was to obtain a core body of substantiating data which will support approval for use on commercial transports of a technology that is being widely used by the military. The data showed that the doublers had excellent performance

Mortality in people with dementia, delirium and unspecified cognitive impairment in the general hospital:prospective cohort study of 6724 patients with two years follow-up

Purpose: Cognitive impairment is common in older people admitted to hospital, but the outcomes are generally poorly understood, and previous research has shown inconsistent associations with mortality depending on the type of cognitive impairment examined and duration of follow-up. This study examines mortality in older people with any cognitive impairment during acute hospital admission. Patients and methods: Prospective cohort of 6,724 people aged ≥65 years with a structured cognitive assessment on acute admission were included in this study. Cognitive spectrum disorder (CSD) was defined as delirium alone, known dementia alone, delirium superimposed on known dementia, or unspecified cognitive impairment. Mortality associated with different types of CSD was examined using a non-proportional hazards model with 2-year follow-up. Results: On admission, 35.4% of patients had CSD, of which 52.6% died within 2 years. After adjustment for demographics and comorbidity, delirium alone was associated with increased mortality in the 6 months post-admission (HR =1.45, 95% CI 1.28–1.65) and again after 1 year (HR =1.44, 95% CI 1.17–1.77). Patients with known dementia (alone or with superimposed delirium) had increased mortality only after 3 months from admission (HR =1.85, 95% CI 1.56–2.18 and HR =1.80, 95% CI 1.52–2.14) compared with patients with unspecified cognitive impairment after 6 months (HR =1.55, 95% CI 1.21–1.99). Similar but partially attenuated associations were seen after adjustment for functional ability. Conclusion: Mortality post-admission is high in older people with CSD. Immediate risk is highest in those with delirium, while dementia or unspecified cognitive impairment is associated with medium- to long-term risk. These findings suggest that individuals without dementia who develop delirium are more seriously ill (have required a larger acute insult in order to precipitate delirium) than those with pre-existing brain pathology (dementia). Further research to explain the mortality patterns observed is required in order to translate the findings into clinical care

Bone Morphogenetic Protein-Transduced Human Fibroblasts Convert to Osteoblasts and Form Bone in Vivo

Experimental cell or ex vivo gene therapy for localized bone formation typically uses osteoprogenitor cells propagated from periosteum or bone marrow. Both require bone or marrow biopsies to obtain cells. We have demonstrated that implantation of gingival or dermal fibroblasts transduced with BMP ex vivo, using a recombinant adenovirus (AdCMVBMP) attached to porous biodegradable scaffolds, form bone in vivo. Here we show that BMP-7-transduced fibroblasts suspended in injectable thermoset hydrogels form complete ossicles on subcutaneous injection and repair segmental defects in rat femurs. Bone formation was preceded by an intermediate cartilage stage. To determine the fate of the implanted transduced cells, thermoset hydrogel suspensions of ex vivo BMP-7-transduced or nontransduced fibroblasts were placed in diffusion chambers and implanted to allow development in vivo without direct contact with host cells. Only the BMP-transduced fibroblasts formed bone within the diffusion chambers in vivo, revealing that BMP transduction induces osteoblastic conversion of these cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63216/1/107632702760184709.pd

Gene therapy for bone formation: In vitro and in vivo osteogenic activity of an adenovirus expressing BMP7

Bone morphogenetic proteins (BMPs) are well-established agents for inducing orthotopic and ectopic bone formation. However, their clinical usefulness as regenerative agents may be limited by a short in vivo half-life and low specific activity. BMP gene therapy is an alternative route for exploiting the bone-inductive activity of this class of molecules. To test the feasibility of this approach, we examined the osteogenic activity of AdCMV-BMP7, an adenovirus containing BMP7 cDNA under control of the CMV promoter that was constructed using Cre/ lox recombination (Hardy et al. [1997] J. Virol. 71:1842–1849). Adenovirus vectors were shown to readily infect a wide variety of cell types in vitro including osteoblasts, fibroblasts, and myoblasts. COS7 cells transduced with AdCMV-BMP7 produced high levels of BMP-7 (approximately 0.5 Μg/10 6 cells). Furthermore, transduction of C2C12 murine myoblast cells with AdCMVBMP-7 suppressed the muscle phenotype and induced in vitro osteoblast differentiation. To test its in vivo biological activity, AdCMV-BMP7 was mixed with a bovine bone-derived collagen carrier (10 8 plaque-forming units virus/site) and was implanted into mouse muscle and dermal pouches. In both cases, an ossicle containing cortical and trabecular bone and a clearly defined marrow cavity formed at the site of virus implantation within 4 weeks. These data demonstrate that AdCMV-BMP7 transduced cells produce biologically active BMP-7 both in vitro and in vivo and show that gene therapy by direct viral transduction using a virus/matrix implant may be a viable route for stimulating bone regeneration. J. Cell. Biochem. 78:476–486, 2000. © 2000 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34900/1/12_ftp.pd

Recognizing the same face in different contexts : Testing within-person face recognition in typical development and in autism

Unfamiliar face recognition follows a particularly protracted developmental trajectory and is more likely to be atypical in children with autism than those without autism. There is a paucity of research, however, examining the ability to recognize the same face across multiple naturally varying images. Here, we investigated within-person face recognition in children with and without autism. In Experiment 1, typically developing 6- and 7-year-olds, 8- and 9-year-olds, 10- and 11-year-olds, 12- to 14-year-olds, and adults were given 40 grayscale photographs of two distinct male identities (20 of each face taken at different ages, from different angles, and in different lighting conditions) and were asked to sort them by identity. Children mistook images of the same person as images of different people, subdividing each individual into many perceived identities. Younger children divided images into more perceived identities than adults and also made more misidentification errors (placing two different identities together in the same group) than older children and adults. In Experiment 2, we used the same procedure with 32 cognitively able children with autism. Autistic children reported a similar number of identities and made similar numbers of misidentification errors to a group of typical children of similar age and ability. Fine-grained analysis using matrices revealed marginal group differences in overall performance. We suggest that the immature performance in typical and autistic children could arise from problems extracting the perceptual commonalities from different images of the same person and building stable representations of facial identity

Bullets over ballots: Islamist groups, the state and electoral violence in Egypt and Morocco

This article is concerned with state-sponsored electoral violence in liberalized autocracies. The first section of the paper identifies a number of variables that can help explain the decision calculus of authoritarian incumbents to deploy force against strong electoral challengers. The second section then examines these propositions with reference to Egypt and Morocco. Drawing on recent parliamentary elections in both countries the article questions why, despite facing the challenge of political Islam, the two regimes differed so markedly in their willingness to manipulate the polls by recourse to violence. Whilst the Egyptian authorities decided to abrogate all pretence of peaceful elections in favour of violent repression against the Muslim Brotherhood candidates and sympathizers, no such tactics were deployed by the ruling elite in Morocco. We suggest that three principal factors influenced the regimes' response to this electoral challenge: (1) the centrality of the elected institution to authoritarian survival; (2) the availability of alternative electioneering tools; and (3) the anticipated response of the international community. The article concludes by suggesting that in order to understand better when and how states deploy violence in elections, we need to focus on a more complex set of factors rather than simply on the electoral potency of key opposition challengers or the authoritarian nature of the state