| 1. |
- Isola, M., et al.
(författare)
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Subcellular distribution of melatonin receptors in human parotid glands
- 2013
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Ingår i: Journal of Anatomy. - : Wiley. - 0021-8782. ; 223:5, s. 519-524
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Tidskriftsartikel (refereegranskat)abstract
- The hormone melatonin influences oral health through a variety of actions, such as anti-inflammatory, anti-oxidant, immunomodulatory and antitumour. Many of these melatonin functions are mediated by a family of membrane receptors expressed in the oral epithelium and salivary glands. Using immunoblotting and immunohistochemistry, recent studies have shown that the melatonin membrane receptors, MT1 and MT2, are present in rat and human salivary glands. To date, no investigation has dealt with the ultrastructural distribution of the melatonin receptors. This was the aim of the present study, using the immunogold method applied to the human parotid gland. Reactivity to MT1 and, with less intensity, to MT2 appeared in the secretory granules of acinar cells and in the cytoplasmic vesicles of both acinar and ductal cells. Plasma membranes were also stained, albeit slightly. The peculiar intracytoplasmic distribution of these receptors may indicate that there is an uptake/transport system for melatonin from the circulation into the saliva.
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| 2. |
- Wadt, K. A. W., et al.
(författare)
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A recurrent germline BAP1 mutation and extension of the BAP1 tumor predisposition spectrum to include basal cell carcinoma
- 2015
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Ingår i: Clinical Genetics. - : Wiley. - 0009-9163. ; 88:3, s. 267-272
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Tidskriftsartikel (refereegranskat)abstract
- We report four previously undescribed families with germline BRCA1-associated protein-1 gene (BAP1) mutations and expand the clinical phenotype of this tumor syndrome. The tumor spectrum in these families is predominantly uveal malignant melanoma (UMM), cutaneous malignant melanoma (CMM) and mesothelioma, as previously reported for germline BAP1 mutations. However, mutation carriers from three new families, and one previously reported family, developed basal cell carcinoma (BCC), thus suggesting inclusion of BCC in the phenotypic spectrum of the BAP1 tumor syndrome. This notion is supported by the finding of loss of BAP1 protein expression by immunochemistry in two BCCs from individuals with germline BAP1 mutations and no loss of BAP1 staining in 53 of sporadic BCCs consistent with somatic mutations and loss of heterozygosity of the gene in the BCCs occurring in mutation carriers. Lastly, we identify the first reported recurrent mutation in BAP1 (p.R60X), which occurred in three families from two different continents. In two of the families, the mutation was inherited from a common founder but it arose independently in the third family.
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| 4. |
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| 5. |
- Loy, F., et al.
(författare)
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The antipsychotic amisulpride: ultrastructural evidence of its secretory activity in salivary glands
- 2014
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Ingår i: Oral Diseases. - : Wiley. - 1354-523X. ; 20:8, s. 796-802
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveAmisulpride is reported to inhibit clozapine-induced sialorrhea. Preclinically, clozapine evokes muscarinic-M1-type-mediated secretion that, however, amisulpride does not reduce. Instead, amisulpride, without causing any overt secretion per se, enhances both nerve- and autonomimetic-evoked salivation by unknown mechanism(s). Hypothesizing that amisulpride prepares the gland for secretion, we looked for ultrastructural events indicating secretory activity in intercellular canaliculi of serous/seromucous cells, that is, density increase in protrusions (reflecting anchored granules) and in microbuds (reflecting recycling membranes and/or vesicle secretion) and decrease in microvilli (reflecting the cytoskeletal re-arrangement related to exocytosis). Material and MethodsRat parotid and submandibular glands were exposed to amisulpride in vivo or in vitro. Glands were processed for transmission electron and scanning electron microscopy and then morphometrically assessed. ResultsCells were packed with secretory granules. The density of protrusions increased in both glands, whereas significant and parallel changes in microvilli and microbuds occurred only in parotid glands, and in vitro. ConclusionsAmisulpride induced ultrastructural signs of secretory activity but to varying extent; in submandibular glands, in contrast to parotid glands, changes were not brought beyond the granular anchoring stage. Amisulpride may provide an overall readiness for secretion that will result in augmented responses to agonists, a phenomenon of potential interest in dry-mouth treatment.
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| 6. |
- Loy, F., et al.
(författare)
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Ultrastructural evidence of a secretory role for melatonin in the human parotid gland
- 2015
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Ingår i: Journal of Physiology and Pharmacology. - 0867-5910. ; 66:6, s. 847-853
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Tidskriftsartikel (refereegranskat)abstract
- In vivo animal studies show that pentagastrin, cholecystokinin and melatonin cause the secretion and synthesis of salivary proteins. Melatonin occurs in large amounts in the gut and is released into the blood on food intake. In vitro experiments suggest that pentagastrin exerts secretory activity in human salivary glands, as judged by ultrastructural changes, reflecting secretion, and an actual protein output. Currently, it is hypothesised that melatonin induces secretory exocytotic events in the human parotid gland. Human parotid tissues were exposed to a high single concentration of melatonin in vitro, processed for high resolution scanning electron microscopy and then assessed morphometrically with the emphasis on the membrane of the intercellular canaliculi, a site of protein secretion. Compared with controls and in terms of density, the melatonin-exposed parotid tissues displayed increases in protrusions (signalling anchored granules) and microbuds (signalling membrane recycling and/or vesicle secretion) and decreases in microvilli (signalling cytoskeletal re-arrangement related to exocytosis), phenomena abolished or very largely reduced by the melatonin receptor blocker, luzindole. In conclusion, acinar serous cells of parotid tissue displayed in vitro exocytotic activity to melatonin, signalling protein secretion. Whether, under physiological conditions, melatonin influences the secretion of human parotid glands remains to be explored, however.
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| 7. |
- Bousquenaud, M., et al.
(författare)
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Obesity promotes the expansion of metastasis-initiating cells in breast cancer
- 2018
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-542X. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is a strong predictor of poor prognosis in breast cancer, especially in postmenopausal women. In particular, tumors in obese patients tend to seed more distant metastases, although the biology behind this observation remains poorly understood. Methods: To elucidate the effects of the obese microenvironment on metastatic spread, we ovariectomized C57BL/6 J female mice and fed them either a regular diet (RD) or a high-fat diet (HFD) to generate a postmenopausal diet-induced obesity model. We then studied tumor progression to metastasis of Py230 and EO771 grafts. We analyzed and phenotyped the RD and HFD tumors and the surrounding adipose tissue by flow cytometry, qPCR, immunohistochemistry (IHC) and western blot. The influence of the microenvironment on tumor cells was assessed by performing cross-transplantation of RD and HFD tumor cells into other RD and HFD mice. The results were analyzed using the unpaired Student t test when comparing two variables, otherwise we used one-way or two-way analysis of variance. The relationship between two variables was calculated using correlation coefficients. Results: Our results show that tumors in obese mice grow faster, are also less vascularized, more hypoxic, of higher grade and enriched in CD11b(+)Ly6G(+) neutrophils. Collectively, this favors induction of the epithelial-to-mesenchymal transition and progression to claudin-low breast cancer, a subtype of triple-negative breast cancer that is enriched in cancer stem cells. Interestingly, transplanting HFD-derived tumor cells in RD mice transfers enhanced tumor growth and lung metastasis formation. Conclusions: These data indicate that a pro-metastatic effect of obesity is acquired by the tumor cells in the primary tumor independently of the microenvironment of the secondary site.
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| 8. |
- Campus, G, et al.
(författare)
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Six months of daily high-dose xylitol in high-risk schoolchildren: a randomized clinical trial on plaque pH and salivary mutans streptococci.
- 2009
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Ingår i: Caries research. - : S. Karger AG. - 1421-976X .- 0008-6568. ; 43:6, s. 455-61
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Tidskriftsartikel (refereegranskat)abstract
- A randomized clinical trial was designed to evaluate the effect of daily high-dose xylitol chewing gum on plaque pH and salivary mutans streptococci (MS) in a sample of schoolchildren at high risk of caries. The study was performed on 204 subjects (acceptance rate 88.3%). Inclusion criteria were: >1 and <4 carious lesions, and a salivary MS concentration >10(5) CFU/ml. Subjects were randomly assigned to the xylitol or control group. Study design included one examination at baseline (t(0)), one after 3 months of chewing (t(1)), one after 6 months of chewing (t(2)) and the last 3 months after the end of chewing period (t(3)). Plaque pH was assessed using the MicroTouch technique, following a sucrose challenge. The area under the curve (AUC(5.7) and AUC(6.2)) was recorded. Whole saliva was collected in sterile vials and MS CFU/ml were counted. Data were analysed using repeated-measures ANOVA. The main result was that plaque acidogenicity was reduced in both groups. The differences between treatments were statistically significant both for plaque pH and MS concentration; the interaction term for treatment and time was statistically significant (p < 0.01). At t(2), the xylitol group children with a salivary MS concentration >10(5) and those with < or =10(5) showed significantly lower AUC(5.7) and AUC(6.2) values than the control group. These results suggest that the long-term use of high-dose non-sucrose chewing gums had beneficial effects on plaque pH, and that this effect was statistically greater when using xylitol chewing gums, both on plaque pH and MS salivary concentration.
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| 10. |
- Fryk, Emanuel, et al.
(författare)
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Hyperinsulinemia and insulin resistance in the obese may develop as part of a homeostatic response to elevated free fatty acids: A mechanistic case-control and a population-based cohort study
- 2021
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Ingår i: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 65
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is commonly accepted that in obesity free fatty acids (FFA) cause insulin resistance and hyperglycemia, which drives hyperinsulinemia. However, hyperinsulinemia is observed in subjects with normoglycaemia and thus the paradigm above should be reevaluated. Methods: We describe two studies: MD-Lipolysis, a case control study investigating the mechanisms of obesity-driven insulin resistance by a systemic metabolic analysis, measurements of adipose tissue lipolysis by microdialysis, and adipose tissue genomics; and POEM, a cohort study used for validating differences in circulating metabolites in relation to adiposity and insulin resistance observed in the MD-Lipolysis study. Findings: In insulin-resistant obese with normal glycaemia from the MD-Lipolysis study, hyperinsulinemia was associated with elevated FFA. Lipolysis, assessed by glycerol release per adipose tissue mass or adipocyte surface, was similar between obese and lean individuals. Adipose tissue from obese subjects showed reduced expression of genes mediating catecholamine-driven lipolysis, lipid storage, and increased expression of genes driving hyperplastic growth. In the POEM study, FFA levels were specifically elevated in obese-overweight subjects with normal fasting glucose and high fasting levels of insulin and C-peptide. Interpretation: In obese subjects with normal glycaemia elevated circulating levels of FFA at fasting are the major metabolic derangement candidate driving fasting hyperinsulinemia. Elevated FFA in obese with normal glycaemia were better explained by increased fat mass rather than by adipose tissue insulin resistance. These results support the idea that hyperinsulinemia and insulin resistance may develop as part of a homeostatic adaptive response to increased adiposity and FFA. (C) 2021 The Author(s). Published by Elsevier B.V.
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