Biomedical subjects

Mark A Reynolds

Publications and source records attributed to Mark A Reynolds.

8 recordsLinked to original sources

PubMed2003

Immunohistochemical expression of angiogenesis-related markers in oral squamous cell carcinomas with multiple metastatic lymph nodes.

The aim of this study was to evaluate the histopathologic features and the expression of angiogenesis-related markers in primary tumors and metastatic lymph nodes of oral squamous cell carcinomas (SCCs) with multiple lymph node involvement in comparison with oral SCCs without nodal metastasis. The protein levels of the angiogenesis inhibitor endostatin, as well as those of the related molecules collagen XVIII, collagen-binding protein (CBP) 2/heat shock protein (HSP) 47, and cathepsin L, were evaluated by immunohistochemical analysis. Compared with nonmetastatic cases, primary tumors of the metastatic group exhibited significantly decreased protein levels of endostatin and its precursor collagen XVIII. Comparison between primary tumors and positive nodes of the metastatic cases revealed decreased expression of collagen XVIII and CBP2/HSP47 in metastases. Angiogenesis is essential for tumor growth and metastasis; accordingly, the observed differences in the immunohistochemical expression of angiogenesis-related proteins in oral SCC with multiple lymph node involvement may provide an explanation for the increased metastatic potential of these tumors.

Adult↗

PubMed2003

Formation of mucogingival defects associated with intraoral and perioral piercing: case reports.

BACKGROUND: The authors provide clinical findings in five patients wearing oral jewelry to illustrate the risks of experiencing periodontal injury associated with body piercing involving intraoral and perioral sites. They also present a literature review of other adverse dental and medical consequences attributed to oral piercing. CASE DESCRIPTIONS: Five young adult patients with tongue and lip piercing sought dental care. Each patient exhibited some degree of gingival recession and mucogingival defects in proximity of their oral jewelry. Three of these patients had probing depths ranging from 5 to 8 millimeters in the affected areas. CLINICAL IMPLICATIONS: Intraoral and perioral jewelry may be associated with the development of significant mucogingival deformities. Because severe attachment loss can develop even when gingival recession is minimal, it is critical that patients with oral piercing routinely undergo comprehensive periodontal assessment. The authors urge clinicians to educate patients about the potential risks regarding the practice of oral piercing.

Adult↗

PubMed2003

The segmental osteotomy in the management of malposed implants: a case report and literature review.

BACKGROUND: The segmental osteotomy provides an important treatment approach for the correction of skeletal-dental malocclusions that would otherwise be unmanageable with conventional orthodontic care. The combined use of orthodontics and orthognathic surgery also has been adapted for use in the correction of developmental and traumatic deformities. Severely malpositioned implant fixtures may not permit restorative correction even with custom prosthetic appliances. As an alternative to implant removal, which can be associated with significant alveolar destruction, orthognathic surgery may offer a treatment modality to improve fixture alignment, thereby enabling a more favorable esthetic and functional prosthesis. This paper presents a case report and review of the segmental osteotomy procedure. METHODS: A 32-year-old female with congenitally missing maxillary lateral incisors underwent implant surgery for prosthetic replacement of these teeth. Due to severe labial positioning of the implant fixtures, acceptable prosthetic treatment was not possible. A segmental osteotomy procedure was used to reposition the implants. The implants were splinted using a ridged interim suprastructure during the 4-month healing period. An occlusal appliance also was worn during the initial 8 weeks of this healing period. RESULTS: The surgical procedure permitted intrusion and palatal repositioning of the implants. Healing proceeded with no untoward effects. Clinical findings at second-stage surgery were consistent with complete osseous repair and integration of the fixtures. Successful prosthetic treatment was subsequently completed for the patient. CONCLUSION: The segmental osteotomy may provide an alternative treatment to the removal of severely malposed implants or their compromised prosthetic restoration.

Adult↗

PubMed2002

PPARgamma-mediated antineoplastic effect of NSAID sulindac on human oral squamous carcinoma cells.

There is strong evidence that nonsteroidal antiinflammatory drug (NSAID) sulindac may exert a significant antineoplastic effect. The purpose of our study was to explore the effects of sulindac on human oral squamous cell carcinoma (SCCa) cells and to elucidate the underlying molecular mechanisms. The changes that sulindac treatment induced on growth, apoptosis and cell cycle distribution of human oral SCCa cell lines were assessed by cell growth and flow cytometry experiments. Utilizing quantitative RT-PCR and immunocytochemistry, we determined the effect of sulindac treatment on mRNA and protein expression of different sulindac's targets. Also, PPARgamma expression was selectively targeted by antisense oligonucleotide treatment. Both sulfide and sulfone metabolites of sulindac, which differ in the ability to cause COX-2 inhibition, induced a significant dose- and time-dependent cell growth reduction accompanied by increase in apoptosis without concomitant cell cycle arrest. Sulindac treatment also caused upregulation of the protein and mRNA expression levels of COX-2 and PPARs. Treatment with antisense PPARgamma oligonucleotides abolished sulindac's growth inhibitory effect. Our results are consistent with a significant growth inhibitory effect of NSAID sulindac on human oral SCCa cells, which is mediated, at least partially, through induction of apoptosis. We suggest that upregulation of PPARgamma expression and activation may be, at least partially, responsible for sulindac's antiproliferative effect.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2002

Microarray technology GEM microarrays and drug discovery.

Incyte Genomics' GEM Gene Expression Microarray is a proven genomics tool used by a large number of pharmaceutical companies to speed up the drug discovery and development process. The development and integration of this technology, together with Incyte's sequence databases and clone resources, have resulted in GEM microarrays that span approximately 60,000 human genes as well as approximately 60,000 plant, rat, mouse, yeast, and bacterial genes. The technology underlying the use of these arrays and their application to the drug discovery process is highlighted.

Drug Design↗

PubMed2002

Biomarkers predictive of lymph node metastases in oral squamous cell carcinoma.

PURPOSE: The ability of oral squamous cell carcinoma to metastasize to lymph nodes does not always show a relationship with clinical staging. The aim of this study was to attempt to define a trend for predictive histopathologic and/or molecular biomarkers in the development of nodal metastasis by analyzing 2 clinically extreme groups. PATIENTS AND METHODS: Patients with small primary tumors (T1, T2) with lymph node metastasis and patients with large primary tumors (T3, T4) without metastatic disease were identified among 315 consecutive cases of primary oral squamous cell carcinoma. Group comparisons were made with use of a Mann-Whitney test, and associations among the variables were assessed with nonparametric and parametric correlational analyses. RESULTS: The degree of keratinization was significantly less in primary tumors with lymph node metastasis (P < or = .01). The degree of keratinization was significantly associated with nuclear pleomorphism (P =.02), number of mitoses (P =.02), stage of invasion (P =.002), and p53 expression (P =.04), independent of clinical stage of the tumor. Other microscopic features and immunohistochemical markers did not differ significantly between the groups (P >.05). CONCLUSION: These data indicate that there still is no single predictive parameter superior to the degree of keratinization to identify patients at risk for the development of regional metastasis.

Adult↗

PubMed2002

A retrospective case series comparing the use of demineralized freeze-dried bone allograft and freeze-dried bone allograft combined with enamel matrix derivative for the treatment of advanced osseous lesions.

BACKGROUND: Combined regenerative approaches have been used for treating advanced osseous lesions around teeth. The aim of combining treatments is to enhance both clinical predictability and regenerative outcome compared to a monotherapeutic approach. This case series from a private practice reports on the clinical efficacy of an enamel matrix derivative (EMD) combined with either demineralized freeze-dried bone allograft (DFDBA) or freeze-dried bone allograft (FDBA) in the treatment of advanced infrabony lesions. The advanced lesions were veneered by a rapidly formed absorbable polymer barrier of poly(DL-lactide) to enhance graft containment. METHODS: A total of 22 consecutive patients, each contributing one infrabony lesion, are reported. After patients completed presurgical preparation, the infrabony lesions were surgically treated with a combined approach that included root surface treatment with citric acid. The two groups differed in their composite graft; one received DFDBA-EMD (n = 10) and the other received FDBA-EMD (n = 12). Patients followed a stringent postoperative protocol and were evaluated 6 months postsurgery. Clinical outcomes were assessed by changes in clinical attachment level (CAL) and probing depth (PD) from pretreatment. Surgical re-entry of several sites was possible in each group. RESULTS: CAL at pretreatment measured 9.2 +/- 1.3 mm and 9.1 +/- 1.9 mm for DFDBA-EMD and FDBA-EMD groups, respectively, with corresponding PD of 8.4 +/- 1.6 mm and 8.9 +/- 2.0 mm for each group. At 6 months post-treatment, CALs were reduced to 4.7 +/- 1.3 mm and 3.8 +/- 1.0 mm for DFDBA-EMD and FDBA-EMD groups, respectively; with corresponding PD decreased to 3.0 +/- 0.8 mm and 3.2 +/- 1.0 mm. Relative improvements in CAL for the DFDBA-EMD and DFDBA-EMD groups were 49.1% +/- 11.0% and 57.3% +/- 9.4%, respectively (P <0.07). CONCLUSIONS: This case series demonstrates the clinical benefits of using a combined therapeutic approach in which a biologic mediator (EMD) was combined with either DFDBA or FDBA. In this limited case series, a trend was observed towards greater improvement in clinical attachment level gain in advanced infrabony defects when EMD was combined with FDBA as compared to DFDBA. Larger prospective controlled clinical trials are needed to determine if differences exist in the relative efficacy of DFDBA versus FDBA in combination with EMD.

Absorbable Implants↗

PubMedDate not supplied

An efficient binding chemistry for glass polynucleotide microarrays.

A variety of methods have been described for making synthetic polynucleotide microarrays. These include in situ synthesis directly on the array surface, for example, by photolithography or ink-jet printing technologies, and the application of presynthesized polynucleotides that are derivatized with various nucleophiles or electrophiles. In the latter case, a variety of surface chemistries have been developed, and several are available commercially. These chemistries must be compatible with nanoliter-scale volumes of polynucleotide reagents, which contact the array over a small portion of their surface. We reasoned that a three-dimensional polymer coating could potentially offer greater surface contact and higher binding efficiency. Here we describe a polyethylenimine-based coating chemistry that provides exceptional binding and hybridization characteristics. In our preferred process, size-fractionated polyethylenimine polymers are cross-linked onto an aminopropylsilanated glass surface in the presence of cyanuric chloride. The resulting three-dimensional coating binds polynucleotides through a mixture of covalent and noncovalent interactions as evidenced by comparisons between 5'-aminoalkyl modified and unmodified polynucleotides. Binding and hybridization comparisons are presented including analogous two-dimensional electrophilic and electrostatic chemistries.

Algorithms↗