Papillon-Lefèvre syndrome (PLS) is an autosomal recessive disorder characterised by palmoplantar hyperkeratosis and severe early onset periodontitis that results in the premature loss of the primary and secondary dentitions. A major gene locus for PLS has been mapped to a 2.8 cM interval on chromosome 11q14. Correlation of physical and genetic maps of this interval indicate it includes at least 40 ESTs and six known genes including the lysosomal protease cathepsin C gene (CTSC). The CTSCmessage is expressed at high levels in a variety of immune cells including polymorphonuclear leucocytes, macrophages, and their precursors. By RT-PCR, we found CTSC is also expressed in epithelial regions commonly affected by PLS, including the palms, soles, knees, and oral keratinised gingiva. The 4.7 kbCTSC gene consists of two exons. Sequence analysis of CTSC from subjects affected with PLS from five consanguineous Turkish families identified four different mutations. An exon 1 nonsense mutation (856C→T) introduces a premature stop codon at amino acid 286. Three exon 2 mutations were identified, including a single nucleotide deletion (2692delA) of codon 349 introducing a frameshift and premature termination codon, a 2 bp deletion (2673-2674delCT) that results in introduction of a stop codon at amino acid 343, and a G→A substitution in codon 429 (2931G→A) introducing a premature termination codon. All PLS patients were homozygous for cathepsin C mutations inherited from a common ancestor. Parents and sibs heterozygous for cathepsin C mutations do not show either the palmoplantar hyperkeratosis or severe early onset periodontitis characteristic of PLS. A more complete understanding of the functional physiology of cathepsin C carries significant implications for understanding normal and abnormal skin development and periodontal disease susceptibility.

Of the many palmoplantar keratoderma (PPK) conditions, only Papillon-Lefèvre syndrome (PLS) and Haim-Munk syndrome (HMS) are associated with premature periodontal destruction. Although both PLS and HMS share the cardinal features of PPK and severe periodontitis, a number of additional findings are reported in HMS including arachnodactyly, acro-osteolysis, atrophic changes of the nails, and a radiographic deformity of the fingers. While PLS cases have been identified throughout the world, HMS has only been described among descendants of a religious isolate originally from Cochin, India. Parental consanguinity is a characteristic of many cases of both conditions. Although autosomal recessive transmission of PLS is evident, a more “complex” autosomal recessive pattern of inheritance with phenotypic influences from a closely linked modifying locus has been hypothesised for HMS. Recently, mutations of the cathepsin C gene have been identified as the underlying genetic defect in PLS. To determine if a cathepsin C mutation is also responsible for HMS, we sequenced the gene in affected and unaffected subjects from the Cochin isolate in which both the PLS and HMS phenotypes appear. Here we report identification of a mutation of cathepsin C (exon 6, 2127A→ G) that changes a highly conserved amino acid in the cathepsin C peptide. This mutation segregates with HMS in four nuclear families. Additionally, the existence of a shared common haplotype for genetic loci flanking the cathepsin C gene suggests that affected subjects descended from the Cochin isolate are homozygous for a mutation inherited “identical by descent” from a common ancestor. This finding supports simple autosomal recessive inheritance for HMS in these families. We also report a mutation of the same exon 6CTSC codon (2126C→T) in a Turkish family with classical PLS. These findings provide evidence that PLS and HMS are allelic variants of cathepsin C gene mutations.

We developed a new product called titanium-prepared platelet-rich fibrin (T-PRF). The T-PRF method is based on the hypothesis that titanium may be more effective in activating platelets than the silica activators used with glass tubes in Chouckroun’s leukocyte- and platelet-rich fibrin (L-PRF) method. In this study, we aimed to define the structural characteristics of T-PRF and compare it with L-PRF. Blood samples were collected from 10 healthy male volunteers. The blood samples were drawn using a syringe. Nine milliliters was transferred to a dry glass tube, and 9 mL was transferred to a titanium tube. Half of each clot (i.e., the blood that was clotted using T-PRF or L-PRF) was processed with a scanning electron microscope (SEM). The other half of each clot was processed for fluorescence microscopy analysis and light microscopy analysis. The T-PRF samples seemed to have a highly organized network with continuous integrity compared to the other L-PRF samples. Histomorphometric analysis showed that T-PRF fibrin network covers larger area than L-PRF fibrin network; also fibrin seemed thicker in the T-PRF samples. This is the first human study to define T-PRF as an autogenous leukocyte- and platelet-rich fibrin product. The platelet activation by titanium seems to offer some high characteristics to T-PRF.

Background: Drug‐induced gingival overgrowth is a known side effect of certain chemotherapeutic agents used for the treatment of systemic disorders. The pathogenesis and mechanisms responsible for this condition are not fully understood. This study assesses for the presence and localization of connective tissue growth factor (CTGF) in drug‐induced gingival overgrowth tissues. CTGF immunostaining was compared with sections stained with transforming growth factor (TGF)‐β1 and CD31 antibodies in order to investigate possible pathogenic mechanisms.Methods: Gingival overgrowth samples were obtained from patients undergoing therapy with phenytoin (n = 9), nifedipine (n = 4), cyclosporin A (n = 5), and control tissues from systemically healthy donors (n = 9). Tissue sections were subjected to peroxidase immunohistochemistry and were stained with CTGF and TGF‐β1 polyclonal primary antibodies. Possible relationships between CTGF staining and angiogenesis were also studied using an anti‐CD31 antibody as a marker for endothelial cells. Staining was analyzed by computerassisted quantitative and semiquantitative methodology at 5 defined sites in all samples based on the location of specific landmarks including epithelium and underlying connective tissues.Results: Cellular and extracellular CTGF content in phenytoin gingival overgrowth tissues was significantly (P <0.05) higher compared to the other gingival overgrowth tissues and the controls. Higher CTGF staining in phenytoin gingival overgrowth tissues was accompanied by an increased abundance of fibroblasts and connective tissue fibers. No strong association of CTGF staining with TGF‐β1 or CD31 staining was found.Conclusions: The data from the present study show significantly higher CTGF staining in phenytoin‐induced gingival overgrowth tissues compared to controls, cyclosporin A‐, or nifedipine‐induced gingival overgrowth. Moreover, semiquantitative analyses of histologic samples support the concept that the phenytoin overgrowth tissues are fibrotic. These associations suggest a possible role for CTGF in promoting development of fibrotic lesions in phenytoin‐induced gingival overgrowth. J Periodontol 2001;72:921‐931.

Background: Monocyte chemoattractant protein‐1 (MCP‐1) is a well‐known chemotactic cytokine that regulates mononuclear inflammatory cell recruitment. This recruitment has particular importance in the oral cavity because inflammatory cells will be challenged with periodontopathogenic bacteria during infections. Tumor necrosis factor‐alpha (TNF‐α) is a cytokine that induces bone resorption by stimulating proliferation and differentiation of osteoclasts’ progenitors and also stimulates MCP‐1 expression. The aims of this study were to investigate the presence of MCP‐1 in gingival crevicular fluid (GCF) samples from patients with chronic periodontitis (CP) and aggressive periodontitis (AgP) and to examine the possible correlations between the GCF levels of MCP‐1 and TNF‐α.Methods: Twenty‐five CP, 20 AgP, and 20 healthy control (C) patients were selected for the study. Plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment level (CAL) measurements were recorded from each sampling area. Assays for GCF MCP‐1 and TNF‐α were carried out by an enzyme‐linked immunosorbent assay (ELISA) method.Results: The concentration (nanograms per microliters) and total MCP‐1 and TNF‐α (nanograms per site) were not statistically significant between CP and AgP groups, but total MCP‐1 and TNF‐α was statistically different between CP and C and between AgP and C groups (P <0.001). All clinical parameters were statistically different between CP and C and between AgP and C groups (P <0.001). A positive statistical correlation was detected between the levels of MCP‐1 and TNF‐α, and there was also a positive correlation between all clinical parameters and total MCP‐1 and TNF‐α levels.Conclusions: These results suggest that MCP‐1 could have an important role in the activation and recruitment of inflammatory and immune cells in periodontal diseases, and both AgP and CP patients may have the same pattern of MCP‐1 expression. A strong positive correlation between the GCF levels of MCP‐1 and TNF‐α may account for the mechanism of amplification of inflammatory events in gingival inflammation.