Saliva flow rates and clinical characteristics of patients with burning mouth syndrome: A case-control study.

Burning mouth syndrome (BMS) is a chronic pain condition that most commonly affects postmenopausal women older than 50 years of age. Xerostomia is a common complaint among BMS patients. However, previous studies showed inconsistent findings regarding saliva flow rate reduction.

Age-related heterogeneity in dental caries and associated risk factors in individuals with cystic fibrosis ages 6-20 years: A pilot study.

Background: The literature conflicts regarding dental caries risk in cystic fibrosis (CF) relative to controls.

Methods: Prospective, observational study of age-related heterogeneity in caries rates and potential risk factors in individuals with CF ages 6-20 at a single clinic in Washington state (N=85). Caries rates for enrolled CF participants and historical controls from NHANES were compared using cubic spline regression models.

Oral Sciences PhD Program Enrollment, Graduates, and Placement: 1994 to 2016.

For decades, dental schools in the United States have endured a significant faculty shortage. Studies have determined that the top 2 sources of dental faculty are advanced education programs and private practice. Those who have completed both DDS and PhD training are considered prime candidates for dental faculty positions.

Application of proteomics to graft-versus-host disease: from biomarker discovery to potential clinical applications.

Graft-versus-host disease (GVHD) is a frequent and potentially life-threatening complication that occurs in many patients who undergo hematopoietic stem cell transplantation. In an effort to develop blood and tissue-based biochemical assays for GVHD diagnosis, high throughput proteomic platforms have been widely utilized for the identification and validation of disease biomarkers for both acute and chronic GVHD. Areas covered: This article reviews biomarker research findings on acute and chronic GVHD ascertained by studying peripheral blood, urine and saliva that gives biological information on systemic or localized disease.

Biology of chronic graft--host disease: Immune mechanisms and progress in biomarker discovery.

Chronic graft--host disease (cGVHD) is the leading cause of long-term morbidity and mortality following allogeneic hematopoietic stem cell transplantation. It presents as a chronic inflammatory and sclerotic autoimmune-like condition that most frequently affects the skin, oral mucosa, liver, eyes and gastrointestinal tract. Both clinical and animal studies have shown that multiple T cell subsets including Th1, Th2, Th17, T follicular helper cells and regulatory T-cells play some role in cGVHD development and progression; B cells also play an important role in the disease including the production of antibodies to HY and nuclear antigens that can cause serious tissue damage.

Unstimulated Saliva-Related Caries Risk Factors in Individuals with Cystic Fibrosis: A Cross-Sectional Analysis of Unstimulated Salivary Flow, pH, and Buffering Capacity.

Salivary flow rate, pH, and buffering capacity are associated with dental caries, but studies from the cystic fibrosis (CF) literature are inconclusive regarding these salivary factors and caries. The aim of this study was to evaluate these factors and their associations with dental caries in individuals with CF. Unstimulated whole saliva was collected from individuals aged 6-20 years at Seattle Children's Hospital CF Clinic, USA (n = 83).

Crystal Structure of Human Profilaggrin S100 Domain and Identification of Target Proteins Annexin II, Stratifin, and HSP27.

The fused-type S100 protein profilaggrin and its proteolytic products including filaggrin are important in the formation of a normal epidermal barrier; however, the specific function of the S100 calcium-binding domain in profilaggrin biology is poorly understood. To explore its molecular function, we determined a 2.2 Å-resolution crystal structure of the N-terminal fused-type S100 domain of human profilaggrin with bound calcium ions.

Proteomic analysis of saliva from patients with oral chronic graft-versus-host disease.

Chronic graft-versus-host disease (cGVHD) is an immune-mediated disorder and is the major long-term complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The oral mucosa, including the salivary glands, is affected in the majority of patients with cGVHD; however, at present there is only a limited understanding of disease pathobiology. In this study, we performed a quantitative proteomic analysis of saliva pooled from patients with and without oral cGVHD-cGVHD(+) and cGVHD(-), respectively-using isobaric tags for relative and absolute quantification labeling, followed by tandem mass spectrometry.

Vitamin D represses dentin matrix protein 1 in cementoblasts and osteocytes.

Calcium and phosphorus homeostasis is achieved by interplay among hormones, including 1,25(OH)2D3 (1,25D), parathyroid hormone, and fibroblast growth factor 23 (FGF23), and their interactions with other proteins. For example, mutations in dentin matrix protein 1 (DMP-1) result in increased FGF23 and hypophosphatemic rickets. 1,25D is reported to modulate FGF23; thus, we hypothesized that 1,25D may be involved in modulating DMP-1 in an intermediary step.

Reduced expression of epidermal growth factor receptor, E-cadherin, and occludin in the skin of flaky tail mice is due to filaggrin and loricrin deficiencies.

Disruption of skin barrier function leads to increases in the percutaneous transfer of allergens and the incidence of atopic dermatitis. Flaky tail (Flg(ft)) mice have been used as a model of atopic dermatitis with skin barrier dysfunction. Although Flg(ft) mice are known to have filaggrin mutation, the mechanism responsible for the skin barrier dysfunction that they display needs to be determined, especially for the roles of epidermal adhesion and junction proteins.

Interaction of the profilaggrin N-terminal domain with loricrin in human cultured keratinocytes and epidermis.

The relationship between the two coexpressed differentiation markers, profilaggrin and loricrin, is not clear right now. In this study, we explored the interaction of profilaggrin N-terminal domain (PND) with loricrin in keratinocytes and epidermis. Confocal immunofluorescence microscopic analysis of human epidermis showed that PND colocalized with loricrin.

Caspase-14 is required for filaggrin degradation to natural moisturizing factors in the skin.

Caspase-14 is a protease that is mainly expressed in suprabasal epidermal layers and activated during keratinocyte cornification. Caspase-14-deficient mice display reduced epidermal barrier function and increased sensitivity to UVB radiation. In these mice, profilaggrin, a protein with a pivotal role in skin barrier function, is processed correctly to its functional filaggrin (FLG) repeat unit, but proteolytic FLG fragments accumulate in the epidermis.

Filaggrin genotype in ichthyosis vulgaris predicts abnormalities in epidermal structure and function.

Although it is widely accepted that filaggrin (FLG) deficiency contributes to an abnormal barrier function in ichthyosis vulgaris and atopic dermatitis, the pathomechanism of how FLG deficiency provokes a barrier abnormality in humans is unknown. We report here that the presence of FLG mutations in Caucasians predicts dose-dependent alterations in epidermal permeability barrier function. Although FLG is an intracellular protein, the barrier abnormality occurred solely via a paracellular route in affected stratum corneum.

Association of a genetic polymorphism (-44 C/G SNP) in the human DEFB1 gene with expression and inducibility of multiple beta-defensins in gingival keratinocytes.

Background: Human beta-defensins (hBDs) are antimicrobial peptides with a role in innate immune defense. Our laboratory previously showed that a single nucleotide polymorphism (SNP) in the 5' untranslated region of the hBD1 gene (DEFB1), denoted -44 (rs1800972), is correlated with protection from oral Candida. Because this SNP alters the putative mRNA structure, we hypothesized that it alters hBD1 expression.

A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming.

Loss-of-function mutations in the FLG (filaggrin) gene cause the semidominant keratinizing disorder ichthyosis vulgaris and convey major genetic risk for atopic dermatitis (eczema), eczema-associated asthma and other allergic phenotypes. Several low-frequency FLG null alleles occur in Europeans and Asians, with a cumulative frequency of approximately 9% in Europe. Here we report a 1-bp deletion mutation, 5303delA, analogous to common human FLG mutations, within the murine Flg gene in the spontaneous mouse mutant flaky tail (ft).

Phosphate regulates osteopontin gene transcription.

Extracellular inorganic phosphate (ePi) is a key regulator of cementoblast behavior, both in vivo and in vitro, and results in a marked increase in osteopontin expression in vitro. To examine the molecular mechanisms involved in ePi induction of osteopontin gene expression, we transfected a series of osteopontin promoter-luciferase constructs into OCCM-30 cementoblasts. Our results demonstrate that ePi can directly induce osteopontin gene transcription.

Caspase-14 protects against epidermal UVB photodamage and water loss.

Caspase-14 belongs to a conserved family of aspartate-specific proteinases. Its expression is restricted almost exclusively to the suprabasal layers of the epidermis and the hair follicles. Moreover, the proteolytic activation of caspase-14 is associated with stratum corneum formation, implicating caspase-14 in terminal keratinocyte differentiation and cornification.

Evidence that TRPC4 supports the calcium selective I(CRAC)-like current in human gingival keratinocytes.

We previously demonstrated that high external [Ca(2+)] activated two Ca(2+) currents in human gingival keratinocytes (HGKs): an initial small I(CRAC)-like current and a second large nonspecific cation current (Fatherazi S, Belton CM, Cai S, Zarif S, Goodwin PC, Lamont RJ, Izutsu KT; Pflugers Arch 448:93-104, 2004). It was recently shown that TRPC1, a member of the transient receptor potential protein family, is a component of the store-operated calcium entry mechanism in keratinocytes. To further elucidate the molecular identity of these channels, we investigated the expression of TRPC4 in gingival tissue and in cultured keratinocytes, and the effect of knockdown of TRPC4 expression on the Ca(2+) currents and influx.

Expression and characterization of constitutively active human caspase-14.

Caspase-14 is a cysteine endoproteinase that is expressed in the epidermis and a limited number of other tissues. It is activated during keratinocyte differentiation by zymogen processing, but its precise function is unknown. To obtain caspase-14 for functional studies, we engineered and expressed a constitutively active form of human caspase-14 (Rev-hC14) in Escherichia coli and cultured mammalian cells.

Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris.

Ichthyosis vulgaris (OMIM 146700) is the most common inherited disorder of keratinization and one of the most frequent single-gene disorders in humans. The most widely cited incidence figure is 1 in 250 based on a survey of 6,051 healthy English schoolchildren. We have identified homozygous or compound heterozygous mutations R501X and 2282del4 in the gene encoding filaggrin (FLG) as the cause of moderate or severe ichthyosis vulgaris in 15 kindreds.

Evidence that TRPC1 contributes to calcium-induced differentiation of human keratinocytes.

External calcium ion concentration is a major regulator of epidermal keratinocyte differentiation in vitro and probably also in vivo. Regulation of calcium-induced differentiation changes is proposed to occur via an external calcium-sensing, signaling pathway that utilizes increases in intracellular calcium ion concentration to activate differentiation-related gene expression. Calcium ion release from intracellular stores and calcium ion influx via store-operated calcium-permeable channels are key elements in this proposed signaling pathway; however, the channels involved have not yet been identified.

TRPC channel expression during calcium-induced differentiation of human gingival keratinocytes.

Background: Extracellular calcium is an important regulator of keratinocyte differentiation. An increase in intracellular calcium ion concentration is required for activation of calcium-induced keratinocyte differentiation. The signaling elements in this differentiation response include the calcium sensing receptor, phospholipase C, release of calcium ions from intracellular stores, and store-operated calcium channels.

A search for CDKN2A/p16INK4a mutations in melanocytic nevi from patients with melanoma and spouse controls by use of laser-captured microdissection.

Objective: To determine the frequency at which the CDKN2A coding region is mutated in the atypical nevi of persons with sporadic melanoma.

Design: DNA samples, isolated by laser-captured microdissection of atypical nevi from 10 patients with newly incident cases of sporadic melanoma and their spouses as matched controls, were used as templates for nested polymerase chain reaction amplification of CDKN2A exons 1 and 2.

Results: No point mutations in the coding region of CDKN2A were observed in any of the melanocytic nevi.