Biochemical analysis of integrin-mediated Shc signaling.
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Animals↗
Biomedical subjects
A Mariotti
Publications and source records attributed to A Mariotti.
BIS-GMA--based resins in dentistry: are they safe?
BACKGROUND: The authors critically surveyed research dealing with the release of resin components from dental composites and the potential of these agents to mimic or disrupt estrogenic cell responses. TYPES OF STUDIES REVIEWED: The studies reviewed included those on synthetic methods used to make bisphenol A glycidyl methacrylate, or BIS-GMA, and the biological effects of this resin in cell culture and animals. The estrogenic effect of bisphenol A was targeted because bisphenol A is present as an impurity in some resins (BIS-GMA) and as a degradation product from other resins (bisphenol A dimethacrylate, or BIS-DMA). RESULTS: The outcomes of this review revealed that short-term administration of BIS-GMA and/or bisphenol A in animals or cell cultures can induce changes in estrogen-sensitive organs or cells. However, considering the dosages and routes of administration and the modest response of estrogen-sensitive target organs, the authors conclude that the short-term risk of estrogenic effects from treatments using bisphenol A-based resins is insignificant. Long-term effects need to be investigated further. CLINICAL IMPLICATIONS: Commonly used dental resins should not be of concern to the general public; however, pharmacological evaluation of dental materials is needed to ensure biologically safe and therapeutically effective substances.
Animals↗
Dental plaque-induced gingival diseases.
Gingival diseases are a diverse family of complex and distinct pathological entities found within the gingiva that are the result of a variety of etiologies. There are several clinical characteristics common to all gingival diseases and these features include clinical signs of inflammation, signs and symptoms that are confined to the gingiva, reversibility of the disease by removing the etiology, the presence of bacterial laden plaque to initiate and/or exacerbate the severity of the disease and a possible role as a precursor for attachment loss around teeth. Defining and classifying gingival diseases has not been an easy task. The tools and methods to identify gingival diseases have varied depending on the criteria used by epidemiologists, researchers, or the practicing clinician. The classification of gingival disease in this review relied upon experimental and/or epidemiological human studies that accurately and reliably assessed an underlying functional derangement that was localized to the gingiva and was reported in a peer-reviewed journal. The classification of gingival diseases that depends on dental plaque to initiate the disease process(es) has been categorized into two groups. The two categories of plaque-induced gingival diseases are those affected by local factors and those that are affected by local factors and modified by specific systemic factors found in the host. In this review, the clinical characteristics of gingival disease associated with plaque, endogenous hormone fluctuations, drugs, systemic diseases, and malnutrition were investigated.
Dental Plaque↗
A requirement for caveolin-1 and associated kinase Fyn in integrin signaling and anchorage-dependent cell growth.
Caveolin-1 functions as a membrane adaptor to link the integrin alpha subunit to the tyrosine kinase Fyn. Upon integrin ligation, Fyn is activated and binds, via its SH3 domain, to Shc. Shc is subsequently phosphorylated at tyrosine 317 and recruits Grb2. This sequence of events is necessary to couple integrins to the Ras-ERK pathway and promote cell cycle progression. These findings reveal an unexpected function of caveolin-1 and Fyn in integrin signaling and anchorage-dependent cell growth.
3T3 Cells↗
The in vivo effects of bisGMA on murine uterine weight, nucleic acids and collagen.
The aim of this investigation was to evaluate the ability of commercial bisGMA to stimulate growth in an estrogen-sensitive target tissue. Adult, female, Swiss-Webster mice were ovariectomized and received either oil, estradiol (100 microg/kg), or one of two bisGMA doses (25 microg/kg or 100 microg/kg). Starting on the day of surgery, the hormone, drug or oil was injected subcutaneously 3 times a week. After 3 wk of treatment, the animals were sacrificed, the uteri removed, weighed and stored at -80 degrees C for biochemical analysis. The uteri from ovariectomized mice receiving high dose (100 microg/kg) bisGMA or estradiol showed a significant increase in normalized wet weight that was 29% and 786%, respectively, greater than the ovariectomized control uterine normalized weights. In the low bisGMA dose (25 microg/kg) group, normalized uterine wet weights were not statistically significant from ovariectomized controls. Biochemical analyses of uterine tissues revealed that estradiol resulted in maintaining DNA content, RNA content, RNA/DNA ratios and collagen content significantly above the ovariectomized control. Neither the low nor high doses of bisGMA stimulated RNA content, DNA content or RNA/DNA ratios above ovariectomized controls. However, the high dose (100 microg/kg) of bisGMA caused a significant increase above ovariectomized controls in uterine collagen content.
Animals↗
Cyclosporin A and hydroxycyclosporine (M-17) affect the secretory phenotype of human gingival fibroblasts.
The responsiveness of human gingival fibroblast populations to cyclosporin A (CsA) and its principal metabolite, hydroxycyclosporine (M17), was evaluated in cell culture. Gingival fibroblasts exhibited a dose-dependent accumulation and bell-shaped distribution of dansylated CsA. A 100-fold excess of non-labeled CsA prevented the accumulation of the fluorescent probe in the fibroblasts. Both CsA (400 ng/ml) and M17 (100 ng/ml) stimulated mean gingival fibroblast cell number to 23.2% and 36.7% above controls, and reduced mean collagen production by 37.7% and 37.4% below controls, respectively; however, neither CsA nor M17 affected mean protein production in comparison to control cultures. Analyses of responses to CsA and M17 by ligand-accumulating and non-accumulating fibroblasts sorted out from the parent cultures did not provide consistent interstrain responses either by cells representing the upper quartile of fluorescence or cells representing the bottom quartiles of fluorescence. These data demonstrate that CsA is accumulated by gingival fibroblasts and that CsA and M17 are potent modulators of gingival fibroblast phenotype.
Adolescent↗
Laboratory principles of implant rehabilitation for fixed prosthesis.
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Dental Prosthesis Design↗
Pharmacologic management of periodontal diseases using systemically administered agents.
Since the establishment of bacteria-laden plaque as a causative agent in gingivitis, the search for specific bacteria that induce different types of periodontitis has generated extensive research. In contrast to many other microbial-induced disorders, the specific periodontal pathogen(s) has not been identified to date. Therefore, the search for an effective systemic agent to prevent the loss of attachment through the selective reduction of known periodontal pathogens has remained elusive. It is not surprising then that antibiotics are not used solely to manage periodontal diseases but rather as an adjunct to the mechanical débridement of root surfaces in select periodontal diseases. Further, the sole use of antibiotics in patients with adult periodontitis (or those who exhibit signs of inflammation but are periodontally stable) has shown little benefit and only increases the chance of microbial resistance to antibiotics. Despite these limitations, considerable progress in antibiotic therapy has delivered regimens that enhance the effectiveness of conventional therapy. In contrast to traditional antimicrobial therapy, new treatment modalities have begun to focus on modulating the responses of host cells to bacteria rather than modulating only the bacteria. Current drugs used to regulate host cells inhibit the cyclooxygenase pathway, reduce the activity of metalloproteinases, or inactivate bone resorptive cells (see Table 1). Although these drugs offer great potential to modulate a variety of mammalian cells, a notable and consequential limitation of these agents is a lack of specificity. Inflammation, bone metabolism, and connective tissue metabolism are two-edged swords; all are necessary for the homeostasis of the tissue, but some or all may also be involved in the pathologic destruction of that same tissue. Hence, drugs that inhibit destruction of the connective tissue in one site of the periodontium also interfere with wound healing at another. As a result of these limitations, the efficacy, safety, and cost-effectiveness of the long-term use of these agents is unknown. Preliminary results of treatment with these drugs are promising, and future generations of host-modulating drugs will provide clinicians with additional agents to help improve the success rate of periodontal treatment for patients. Antibiotics remain an important adjunctive therapy in the treatment of periodontal diseases, and the use of host modulating drugs as supplemental agents in the management of periodontal diseases continues to grow. As more knowledge is gained about the causes of periodontal diseases, new drugs that are potent, effective, site specific, and safe can be delivered at optimal times by simply having the patient take a few tablets. Considering the dramatic progress in the past decade in understanding the cause and pharmacologic management of periodontal diseases, the twenty-first century holds great promise for the development of magic bullets.
Adult↗
Induction of apoptosis by p75 neurotrophin receptor in human neuroblastoma cells.
The low-affinity nerve growth factor receptor p75NTR belongs to a membrane receptor superfamily whose members, in certain cell types, are able to transduce an apoptotic signal. To investigate the effect of p75NTR expression in neuroblastoma cells, we transfected the p75NTR cDNA into SK-N-BE cells, a neuroblastoma cell line that lacks expression of both p75NTR and TrkA. Cell clones expressing elevated levels of p75NTR showed a high degree of cell death by apoptosis, even in serum-supplemented medium. Moreover, the level of apoptosis correlated directly with the expression level of the receptor, indicating that p75NTR could activate the cell death program by itself. Clones expressing p75NTR showed a dramatic increase of cell death when switched into serum-free medium; these cultures rapidly extinguished. This apoptotic effect was greatly inhibited by NGF treatment. Our results support the hypothesis that p75NTR, when it is not bound by NGF, may play a role in neuronal selection during embryonic development and suggest that neuroblastomas may arise from immature neuroblasts that escape programmed cell death. Therefore, the loss of p75NTR expression in developing neural crest cells might be a primary event in the genesis of neuroblastoma.
Apoptosis↗
Molecular preservation and isotopy of Mesolithic human finds from the Ofnet cave (Bavaria, Germany).
Favourable burial conditions and self-limiting decomposition processes led to an extraordinarily well molecular preservation of the Mesolithic human skull finds from the Ofnet cave (district Nördlingen, Bavaria). Beyond the extraction of bone collagen, a selection of serum proteins from bone was identified immunologically. Stable carbon and nitrogen isotope ratios from collagen gave clues to dietary behaviour including nursing practices. Diverging results after the application of biochemical protocols (for protein cleaning) and biophysical methods (for stable isotope analysis) are of particular interest: while the first approach failed to quantitatively eliminate anorganic contaminations, the second left some organic, exogenous residues in the samples. Thus, methods for protein extraction must vary according to problem solution and ultimate aim of the study. Taking this into account, application of invasive methods is also encouraged to rare and valuable skeletal finds.
Blood Proteins↗
Modulation of markers associated with tumor aggressiveness in human breast cancer cell lines by N-(4-hydroxyphenyl) retinamide.
The retinoid N-(hydroxyphenyl) retinamide (4-HPR) appears to be a promising tool for chemoprevention of breast carcinoma, and clinical trials to evaluate its effect are in progress. However, its action on tumor cells has remained largely undefined. We report here that 4-HPR induced apoptosis and/or differentiation in breast cancer cell lines, independent of hormone receptor status and retinoic acid receptor expression, although it was slightly more efficient in inhibiting proliferation of estrogen receptor-positive cells. 4-HPR up-modulated expression of several differentiation markers (class 1 HLA, laminin, and beta 1 integrin chain) and down-regulated expression of molecules associated with tumor progression, including the p185/HER2 oncoprotein, the epidermal growth factor receptor, and the M(r) 67,000 laminin receptor. These data suggest that 4-HPR could exert a beneficial effect by inhibiting cell proliferation and modulating breast tumor aggressiveness.
Anticarcinogenic Agents↗
N-(4-hydroxyphenyl)retinamide: a potent inducer of apoptosis in human neuroblastoma cells.
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Apoptosis↗
Contribution of odd-chain fatty acid oxidation to propionate production in disorders of propionate metabolism.
Whole-body propionate and protein kinetics and energy substrate metabolism were studied in five metronidazole-treated patients with propionic or methylmalonic acidemias by the use of a primed, 4-h constant infusion of [1-13C]propionate and L-[O-2H5]phenylalanine combined with indirect calorimetry. Measurements were performed during fasting and carbohydrate feeding, successively, to assess the contribution of odd-chain fatty acid oxidation to total propionate production. Fat oxidation decreased from 490 +/- 179 to 57 +/- 49 mumol.kg-1.h-1 (P < 0.05) as a result of feeding. Propionate appearance rate was 38.6 +/- 8 mumol.kg-1.h-1 during fasting and decreased to 22.6 +/- 5 mumol.kg-1.h-1 (P < 0.05) on the carbohydrate diet. Precursor amino acid catabolism did not change significantly (22 +/- 5 vs 21.2 +/- 5 mumol.kg-1.h-1), suggesting that the 41% reduction in propionate production observed in response to feeding was related to the suppression of fatty acid oxidation. Therefore, significant therapeutic gains may be expected from the use of diets aimed at reducing lipid oxidation.
Adolescent↗
Sex steroid hormones and cell dynamics in the periodontium.
The biological changes that occur in tissues of the periodontium during puberty, the menstrual cycle, pregnancy, menopause, and oral contraceptive use have heightened interest in the relationship between sex steroid hormones and periodontal health. These clinical observations coupled with tissue specificity of hormone localization, identification of hormone receptors, as well as the metabolism of hormones have strongly suggested that periodontal tissues are targets for androgens, estrogens, and progestins. The etiologies of periodontal endocrinopathies are diverse; nonetheless, periodontal pathologies may be a consequence of the actions and interactions of sex steroid hormones on specific cells found in the periodontium.
Contraceptives, Oral↗
The influence of age on collagen and non-collagen protein production by human gingival epithelial cells.
The effects of donor age on the proliferation and secretory phenotype of cultured human gingival epithelial cells were investigated. Pure cultures of epithelial cells were isolated from human gingiva of old (61-75 yr) and young (18-30 yr) adults and serially cultivated in a serum-free medium at 37 degrees C in humidified air containing 5% CO2. For each experiment, cells were seeded at 150/mm2 and the medium changed every other day. Cell number, collagen and non-collagen protein production and relative collagen synthesis (percentage collagen synthesized) were determined at days 2, 4, 6 and 8. Epithelial strains from old and young adults became confluent by day 8 and there were no differences in their rates of proliferation. Likewise there was no difference in collagen production between the two groups; however, cells from elderly individuals produced significantly less non-collagen protein. Over time the decrease in non-collagen protein production ranged from 56% below the non-collagen protein levels of epithelium from young adults at day 2 to 24% below at day 8. The reduction of non-collagen protein coupled with the unchanged secretion of collagen resulted in a statistically significant increase in relative collagen synthesis by epithelial cells from elderly individuals. These differences in non-collagen protein production and relative collagen synthesis by cultured gingival epithelium of old adults suggest a selective conversion in protein secretion.
Adolescent↗
The extracellular matrix of the periodontium: dynamic and interactive tissues.
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Animals↗
Protein kinases and the androgen-induced proliferation of accessory sex organ smooth muscle.
The possible role of second messenger systems in androgen-dependent smooth muscle proliferation was investigated. Focusing on the hormone-sensitive guinea pig seminal vesicle, we analyzed changes in protein kinase C (PKC) and cAMP-dependent type I and II protein kinases during the androgen-dependent smooth muscle proliferation of puberty, as well as in the transition to the nonproliferative state of the adult. The androgenic sensitivity of the cAMP-dependent type I and II protein kinases and the cAMP-dependent phosphorylations of soluble muscle proteins did not correlate with the qualitative change in the androgenic sensitivity of the prepubertal vs. adult animals. In contrast to the cAMP-dependent protein kinases, regulation of the soluble and particulate forms of PKC corresponded to the androgen-induced smooth muscle proliferation. That is, in the seminal vesicle muscle of prepubertal castrated animals, androgen treatment reduced both the soluble and particulate forms of PKC during the increase in smooth muscle DNA synthesis, and in adult seminal vesicle smooth muscle, which was resistant to androgen-induced proliferation, both forms of the enzyme were resistant to androgenic stimulation. It is concluded that PKC may be a component of an autocrine mitogenic mechanism involved in the coupling and uncoupling of androgen-induced smooth muscle proliferation.
Androgens↗