Biomedical subjects
Publications and source records attributed to Sreenivas Koka.
This clinical report of a fractured cantilevered substructure bar describes an alternative treatment to the proposed refabrication of the substructure bar and overdenture prosthesis. This report outlines the clinical and laboratory procedures to repair the fractured bar, eliminating the time and expense of fabricating a new bar and prosthesis.
Bisphosphonate chemotherapy is commonly used in the treatment of bone diseases such as osteoporosis, Paget disease, and multiple myeloma and to limit bone pain and hypercalcemia associated with malignant metastatic bone lesions. The introduction of bisphosphonate therapy has improved the quality of life in a vast majority of patients, showing clear medical efficacy. However, since 2003 a growing number of reports have described necrotic bone lesions (osteonecrosis of the jaw [ONJ]) affecting maxillofacial bones in patients who have received chemotherapy with intravenous bisphosphonate therapy. Unfortunately, the development of ONJ has been refractory to conventional treatment modalities. Several treatment options have been proposed for ONJ, most of which focus primarily on conservative management with local irrigation and empirical long-term antibiotic therapy. However, results of treatment have been associated with high failure rates, progression of disease, and continued decline in patients' quality of life. We describe 2 patients in whom primary surgical salvage was performed successfully for ONJ. Our experience indicates that with appropriate technique, primary surgical treatment may offer benefit to selected patients with ONJ.
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The mammalian formin homology domain containing protein FHOD1 influences a variety of cellular events including cell migration, cytoskeletal arrangement, signal transduction, and gene expression. In this paper, we show that Src regulates a variety of FHOD1-associated effects. FHOD1 distribution to lamellipodia was prevented by the absence of Src. However, stress fiber formation induced by a C-terminal truncated form of FHOD1 was unaffected. Gene expression from an SRE-dependent promoter and from the skeletal actin promoter was induced by two truncated forms of FHOD1 and in both instances, inhibition of Src tyrosine kinase activity abrogated induction of gene expression. Furthermore, Src activity was necessary to maintain mRNA levels of FHOD1 itself, and as such, this finding represents the first description of mechanisms involved in the regulation of formin gene expression in mammals. In summary, we have identified Src as a key regulator of FHOD1 biology.
Formin homology 2 domain containing protein (FHOD1), a mammalian formin, regulates cytoskeletal architecture, enhances cell migration, and induces gene expression from the serum response element. In this study, we describe co-precipitation of FHOD1 with components of the ERK MAP kinase pathway while co-precipitation of FHOD1 with p38 MAP kinase and JNK was not observed. In addition, FHOD1 co-localized to lamellipodia with Raf-1 and to stress fibers with MEK. FHOD1-induced gene expression from the serum response element was dependent on ERK MAP kinase activation, and the native skeletal actin promoter were activated by FHOD1 through the SRF site. However, FHOD1-induced stress-fiber formation and gene expression from the skeletal actin promoter was independent of ERK activation. These novel data demonstrate that FHOD1-ERK MAP kinase interaction regulates key aspects of FHOD1 biology.
Inflammatory bone diseases are characterized by the presence of pro-inflammatory cytokines that regulate bone turnover. Osteoprotegerin (OPG) is a soluble osteoblast-derived protein that influences bone resorption by inhibiting osteoclast differentiation and activation. In the present study, we demonstrate that interleukin-1beta and tumor necrosis factor alpha induce OPG mRNA production and OPG secretion by osteoblast-like MG-63 cells. Maximum induction of OPG secretion by either cytokine requires activation of the p38 mitogen activated protein kinase (MAPK) pathway but neither the p42/p44 (ERK) nor the c-Jun N-terminal MAPK pathways. Induction of OPG mRNA by either cytokine is also p38 MAPK dependent. Taken together, these data indicate that cytokine-induced OPG gene expression and protein secretion are differentially regulated by specific MAP kinase signal transduction pathways.
Formin homology-2-domain containing protein 1 (FHOD1) regulates gene transcription, actin-cytoskeleton structure, and cell migration. To gain insight into the mechanisms by which FHOD1 mediates these diverse activities, a yeast-two-hybrid screen was performed to identify FHOD1-binding proteins. Three proteins specifically interacted with the carboxy-terminal two-thirds of FHOD1, which includes the FH1, FH2, and diaphanous activating domains (DAD). The newly identified FHOD1-binding proteins are protein kinase C binding protein 1 (PRKCBP1), cyclophilin B, and an isoform of WASP-interacting SH3-domain protein/diaphanous-interacting protein 1 (WISH/DIP1), named WISH-B. The proline-rich FH1 domain of FHOD1 was sufficient to interact with the central portion of PRKCP1 and full-length cyclophilin B. The FH1 domain also interacted with full-length WISH-B, but the extreme amino-terminus was sufficient to associate with WISH-B as well. WISH-B altered the solubility of FHOD1 in vitro and a truncation mutant containing the amino-terminal 227 residues of WISH-B disrupted FHOD1-induced stress fibers. WISH-B did not affect FHOD1-induced gene transcription through the serum response factor (SRF) recognition site on the skeletal alpha actin promoter (SkA). However, stabilization of F-actin prevented FHOD1 dependent activation of this promoter in presence of high, but not low serum concentrations. Thus, the identification of a new FHOD1-binding protein provides insight into the mechanisms by which FHOD1 regulates actin polymerization and transcription.
Formin-homology-domain-containing proteins interact with Rho-family GTPases and regulate actin cytoskeleton organization and gene transcription. FHOD1 is a member of this family, interacts with Rac1 and induces transcription from the serum response element. In this study, we examined the effects of FHOD1 expression on cytoskeletal organization and function in mammalian cells. FHOD1 proteins were stably expressed in WM35 melanoma cells and NIH-3T3 fibroblasts. Cells expressing full-length FHOD1 demonstrated an elongated phenotype compared with vector-transfected cells and cells expressing a truncated FHOD1 (1-421) that lacks the conserved FH1 and FH2 domains. Full-length FHOD1 co-localized with filamentous actin at cell peripheries. Cells transiently expressing a C-terminal FHOD1 truncation mutant (DeltaC, residues 1-1010), which lacks an autoinhibitory protein-protein interaction domain, displayed prominent stress fibers. FHOD1 (1-421) did not induce stress fibers but localized to membrane ruffles in a manner similar to the full-length protein, indicating that the FH1 and FH2 domains are required for stress fiber appearance. FHOD1 DeltaC (1-1010)-dependent stress fibers were sensitive to dominant-negative RacN17 and the RhoA and ROCK inhibitors, C3 transferase and Y-27632. Stable overexpression of full-length FHOD1 enhanced the migration of WM35 and NIH-3T3 cells to type-I collagen and fibronectin, respectively. Cells expressing FHOD1 (1-421) migrated similar to control cells. Integrin expression and activation were not affected by FHOD1 expression. Moreover, FHOD1 overexpression did not alter integrin usage during adhesion or migration. These data demonstrate that FHOD1 interacts with and regulates the structure of the cytoskeleton and stimulates cell migration in an integrin-independent manner.
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Human immunodeficiency virus type 1 (HIV-1) infection is known to cause neuronal injury and dementia in a significant proportion of patients. However, the mechanism by which HIV-1 mediates its deleterious effects in the brain is poorly defined. The present study was undertaken to investigate the effect of the HIV-1 tat gene on the expression of inducible nitric-oxide synthase (iNOS) in human U373MG astroglial cells and primary astroglia. Expression of the tat gene as RSV-tat but not that of the CAT gene as RSV-CAT in U373MG astroglial cells led to the induction of NO production and the expression of iNOS protein and mRNA. Induction of NO production by recombinant HIV-1 Tat protein and inhibition of RSV-tat-induced NO production by anti-Tat antibodies suggest that RSV-tat-induced production of NO is dependent on Tat and that Tat is secreted from RSV-tat-transfected astroglia. Similar to U373MG astroglial cells, RSV-tat also induced the production of NO in human primary astroglia. The induction of human iNOS promoter-derived luciferase activity by the expression of RSV-tat suggests that RSV-tat induces the transcription of iNOS. To understand the mechanism of induction of iNOS, we investigated the role of NF-kappaB and C/EBPbeta, transcription factors responsible for the induction of iNOS. Activation of NF-kappaB as well as C/EBPbeta by RSV-tat, stimulation of RSV-tat-induced production of NO by the wild type of p65 and C/EBPbeta, and inhibition of RSV-tat-induced production of NO by deltap65, a dominant-negative mutant of p65, and deltaC/EBPbeta, a dominant-negative mutant of C/EBPbeta, suggest that RSV-tat induces iNOS through the activation of NF-kappaB and C/EBPbeta. In addition, we show that extracellular signal-regulated kinase (ERK) but not that p38 mitogen-activated protein kinase (MAPK) is involved in RSV-tat induced production of NO. Interestingly, PD98059, an inhibitor of the ERK pathway, and deltaERK2, a dominant-negative mutant of ERK2, inhibited RSV-tat-induced production of NO through the inhibition of C/EBPbeta but not that of NF-kappaB. This study illustrates a novel role for HIV-1 tat in inducing the expression of iNOS in human astrocytes that may participate in the pathogenesis of HIV-associated dementia.
PURPOSE: The paper presents results of a survey of members of the American College of Prosthodontists (ACP) conducted to determine experiences and practices with dental implants. MATERIALS AND METHODS: Preliminary survey questions regarding the prosthetic and surgical use of dental implants were developed. The master list of questions was distributed to communities of interest to establish the most pertinent items of interest. The final questionnaire was distributed to all members of the ACP living or practicing in the United States and members engaged in the U.S. armed services. Responses were compiled and analyzed to determine correlation of responses using the chi-squared test for count data (level of significance alpha = 0.05). Fisher's exact test was applied to all significant responses. RESULTS: Surveys were distributed to 1815 ACP members. A total of 554 (31%) surveys were completed. On the basis of age distribution of survey respondents, it was determined that the respondents were representative of the ACP membership. The majority of the respondents (82%; CI, 79% to 85%) treat patients with implant-supported prostheses, while 12% (CI, 10% to 15%) surgically place implants. Of those not placing implants, 24% reported a desire to place implants, while 43% of all respondents expressed a desire for an ACP-sponsored course in implant placement. Increased age of the prosthodontist correlated negatively with a desire to place implants (p < 0.0001). Dissatisfaction with implant placement by others correlates with willingness to surgically place implants (p < 0.0001). CONCLUSIONS: Most prosthodontists (82%) use implant-supported prostheses in their practices, but most of the implants are placed by non-prosthodontists. There is general satisfaction with implant placement regardless of the specialty of the practitioner placing the implants. Younger prosthodontists expressed a greater desire to surgically place implants but were not statistically more likely to do so.
The reader of oral and maxillofacial implant literature is challenged to be cognizant of the quality of clinical research data. The large variety of possible study designs utilized by clinical researchers requires the reader to have a fundamental awareness of the advantages, disadvantages, and limitations of commonly utilized study designs. This article aims to provide the reader with information to make an informed decision regarding the quality of a clinical research paper, so that he or she can judge whether the information presented in any given manuscript was obtained in a manner that truly minimizes bias, in the form of systematic or random errors, and whether it warrants serious consideration for clinical decision making. Special consideration is given to scientific literature pertaining to the use of oral and maxillofacial implants. In addition, the reader is presented with a method for placing any single manuscript within a "hierarchy of evidence" enabling an "estimate of confidence" in a particular therapy. By utilizing such methods to appraise the quality of research data, clinicians and patients will be better informed when making treatment-planning decisions.
PURPOSE: This literature review was conducted to evaluate the quality of current evidence of clinical performance provided by American Dental Association-certified dental implant manufacturers and manufacturers with strong market penetration in the United States. The study also compared the clinical performance of different dental implant systems. MATERIALS AND METHODS: A letter was sent to 6 implant manufacturers requesting 10 references each that validated the manufacturer's implant system in a variety of clinical applications. References were reviewed and classified relative to strength of evidence. Data extraction was then performed. Comparisons of implant survival data from 5-year studies were made, and data were pooled to establish an overall 5-year survival rate with confidence intervals (CIs). RESULTS: A total of 69 references were provided by the 6 implant manufacturers (Astra Tech, Centerpulse, Dentsply/Friadent, Implant Innovations, Nobel Biocare, and Straumann) but only 59 articles were available for review. Of those references, most were level-4 (case series) or level-5 (expert opinion) articles. Five-year survival data were extracted from 17 articles demonstrating overlap of CIs from the weighted average of the pooled data from each specific manufacturer; substantial equivalence of all implant systems was demonstrated based upon survival alone at 5 years. When all data were pooled, the 5-year survival rate of 96% (CI: 93% to 98%) was observed for a total of 7,398 implants. DISCUSSION: No obvious differences in implant survival were observed when comparing implant systems. CONCLUSIONS: The evidence supporting implant therapy is generally derived from level-4 case series rather than higher-level cohort or controlled clinical trials. Articles that directly compared different implant systems were not found. Five-year implant survival rates easily exceeded the minimums recommended by the American Dental Association certification program. (More than 50 references.)
In this 2-part review series, the current uses of saliva as a diagnostic fluid are reviewed, first with a focus on known measurements of systemic conditions. In Part 2, the role of saliva to measure bone turnover with a special emphasis on osteoporosis will be discussed.
In this 2-part review series, the current uses of saliva as a diagnostic fluid are reviewed. Part 1 focused on known measurements of systemic conditions. In Part 2, the role of saliva to measure bone turnover with a special emphasis on osteoporosis are discussed.
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