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Biomedical subjects

D A Garber

Publications and source records attributed to D A Garber.

At least 19 recordsLinked to original sources

Expression of CCL20 and granulocyte-macrophage colony-stimulating factor, but not Flt3-L, from modified vaccinia virus ankara enhances antiviral cellular and humoral immune responses.

While modified vaccinia virus Ankara (MVA) is currently in clinical development as a safe vaccine against smallpox and heterologous infectious diseases, its immunogenicity is likely limited due to the inability of the virus to replicate productively in mammalian hosts. In light of recent data demonstrating that vaccinia viruses, including MVA, preferentially infect antigen-presenting cells (APCs) that play crucial roles in generating antiviral immunity, we hypothesized that expression of specific cytokines and chemokines that mediate APC recruitment and activation from recombinant MVA (rMVA) vectors would enhance the immunogenicity of these vectors. To test this hypothesis, we generated rMVAs that express murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), human CCL20/human macrophage inflammatory protein 3alpha (hCCL20/hMIP-3alpha), or human fms-like tyrosine kinase 3 ligand (hFlt3-L), factors predicted to increase levels of dendritic cells (DCs), to recruit DCs to sites of immunization, or to promote maturation of DCs in vivo, respectively. These rMVAs also coexpress the well-characterized, immunodominant lymphocytic choriomeningitis virus nucleoprotein (NP) antigen that enabled sensitive and quantitative assessment of antigen-specific CD8(+) T-cell responses following immunization of BALB/c mice. Our results demonstrate that immunization of mice with rMVAs expressing mGM-CSF or hCCL20, but not hFlt3-L, results in two- to fourfold increases of cellular immune responses directed against vector-encoded antigens and 6- to 17-fold enhancements of MVA-specific antibody titers, compared to those responses elicited by nonadjuvanted rMVA. Of note, cytokine augmentation of cellular immune responses occurs when rMVAs are given as primary immunizations but not when they are used as booster immunizations, suggesting that these APC-modulating proteins, when used as poxvirus-encoded adjuvants, are more effective at stimulating naïve T-cell responses than in promoting recall of preexisting memory T-cell responses. Our results demonstrate that a strategy to express specific genetic adjuvants from rMVA vectors can be successfully applied to enhance the immunogenicity of MVA-based vaccines.

Animals↗

Immediate total tooth replacement.

Successful implant placement at the time of extraction has been documented. Implant placement at the time of extraction was initially performed as a two-stage procedure often with barrier membranes and sophisticated second-stage surgical uncoverings. The authors describe the next generation of this technique, including atraumatic tooth removal with simultaneous root form, implant placement, and temporization at one appointment. This technique of "Immediate Total Tooth Replacement" allows for the maintenance of the bony housing and soft-tissue form that existed before extraction, while at the same time establishing a root form anchor in the bone for an esthetic restoration.

Dental Implantation, Endosseous↗

Persistent elevated expression of cytokine transcripts in ganglia latently infected with herpes simplex virus in the absence of ganglionic replication or reactivation.

Infection of mouse trigeminal ganglia by herpes simplex virus induces cytokine expression that persists long after infectious virus or viral antigens become undetectable. To examine mechanisms underlying this phenomenon, we used a thymidine kinase mutant, dlsptk, which fails to replicate in ganglia and does not reactivate upon ganglionic explant. Using quantitative reverse transcriptase-polymerase chain reaction assays, we found that levels of interferon-gamma and tumor necrosis factor-alpha transcripts in dlsptk-infected ganglia were lower than those in wild type-infected ganglia, but were significantly (eight- to 10-fold) higher than those in mock-infected ganglia from Day 3 to Day 100 postinfection. We also studied latency-associated transcript (LAT) negative mutants that exhibit increased expression of productive cycle transcripts in ganglia. Ganglia infected with these mutants contained levels of cytokine transcripts similar to those in wild type-infected ganglia; any increases in viral antigen expression mediated by the LAT deletion were not accompanied by increased cytokine expression. Thus, neither viral replication, the ability to reactivate, nor LAT expression in ganglia is required for persistent elevated cytokine expression. The results provide indirect evidence that low-level expression of viral productive cycle genes in neurons can provide signals that elicit cytokine expression.

Animals↗

Crown lengthening revisited.

Over the last 37 years, crown-lengthening procedures have been used predictably to restore teeth broken down from caries, trauma, and extensive wear. With crown lengthening, the dentogingival junction is "re-created" at a more apical level on the root to accommodate the junctional epithelium and the connective tissue attachment. Forced eruption can be used in addition, or as an alternative, to tooth lengthening. The authors discuss the indications for tooth lengthening, forced eruption, and orthodontic extrusion, as well as the treatment planning for these procedures.

Crown Lengthening↗

Anterior esthetic considerations when splinting teeth.

There are many techniques for stabilizing and splinting teeth. No matter which restorative technique is chosen, the technical elements of marginal fit, psychologic contour, cleansibility, and occlusion must be met. When the restoration is in the esthetic zone of the oral cavity, there is an additional element of achieving an acceptable cosmetic result. This article presents an overview of concepts to achieve acceptable esthetic results when teeth are joined together.

Cuspid↗

Fifty years of interdisciplinary site development: lessons and guidelines from periodontal prosthesis.

Just as "osseointegration" became synonymous with successful restoration of function in the fully edentulous patient during the 1980s, the term "implant site development" has become intricately associated in the 1990s with the techniques used to achieve esthetic results with implants in the partially edentulous patient. This article explores the roots of the concept of site development within the philosophy and principles of periodontal prosthesis. In addition, the myriad of techniques that are presently collectively referred to as site development are systematically classified into a sequential four-tiered approach that optimizes their efficient application as well as overall success.

Dental Prosthesis↗

Treatment planning 2000: an esthetically oriented revision of the original implant protocol.

Soft and hard tissue ridge deformities are prevalent in areas of tooth loss and trauma and can compromise esthetic outcomes. Only a full understanding of the severity of the dimensional defects, the reconstructive techniques available, and the functional and esthetic needs of the final implant restoration will allow the design of a treatment approach that will achieve the desired outcome. This article emphasizes the synergistic relation of the osseous, gingival, and restorative triad in treatment planning. In addition, a systematic approach to the enhancement of this triad, in the partially edentulous patient, is outlined as part of a revised protocol for achieving optimal esthetics in implant therapy.

Dental Implantation↗

A LAT-associated function reduces productive-cycle gene expression during acute infection of murine sensory neurons with herpes simplex virus type 1.

Herpes simplex virus (HSV) persists in the human population by establishing long-term latent infections followed by periodic reactivation and transmission. Latent infection of sensory neurons is characterized by repression of viral productive-cycle gene expression, with abundant transcription limited to a single locus that encodes the latency-associated transcripts (LATs). We have observed that LAT- deletion mutant viruses express viral productive-cycle genes in greater numbers of murine trigeminal ganglion neurons than LAT+ HSV type 1 at early times during acute infection but show reduced reactivation from latent infection. Thus, a viral function associated with the LAT region exerts an effect at an early stage of neuronal infection to reduce productive-cycle viral gene expression. These results provide the first evidence that the virus plays an active role in down-regulating productive infection during acute infection of sensory neurons. The effect of down-regulation of productive-cycle gene expression during acute infection may contribute to viral evasion from the host immune responses and to reduced cytopathic effects, thereby facilitating neuronal survival and the establishment of latency.

Animals↗

Dentist-monitored bleaching: a discussion of combination and laser bleaching.

The traditional power bleaching and matrix bleaching systems offer many advantages for patients. However, each technique also has some drawbacks. This article recommends a combination approach, which uses the best of both systems. The article also discusses the use of lasers and their possible role in bleaching teeth.

Hot Temperature↗

Securing the position of ceramic veneers in dentistry.

Porcelain laminate veneers have exhibited predictability and, as a result, experienced an incredibly rapid public acceptance with widespread utilization. The introduction of a stronger, leucite-reinforced ceramic system which could be accurately pressed (IPS Empress, Ivoclar Williams, Amherst, NY), presented new avenues for this remarkable treatment modality beyond aesthetic enhancement. Porcelain veneer restorations could be utilized to accurately alter and correct occlusal relationships, and the less abrasive surface of the material offered a distinct advantage in occlusal modifications, such as altering cuspal guidance or vertical dimension. This presentation reviews the history of porcelain veneer restoration and outlines the use of a luting cement (Variolink II, Ivoclar Vivadent, Amherst, NY) for its application.

Aluminum Silicates↗

The esthetic dental implant: letting restoration be the guide.

Dental implants originally were placed according to the availability of supportive bone structures. This article describes a new way of approaching implant placement: envisioning the ideal ultimate restoration and developing the treatment plan- and the implant site-to achieve that goal.

Alveolar Bone Loss↗