Calprotectin release from human neutrophils is induced by Porphyromonas gingivalis lipopolysaccharide via the CD-14-Toll-like receptor-nuclear factor kappaB pathway

OBJECTIVES: Calprotectin is a cytosolic protein with antibacterial action in leukocytes and its level increases in some inflammatory diseases, including periodontal diseases, rheumatoid arthritis and ulcerative colitis. Recently, we found that the lipopolysaccharide of Porphyromonas gingivalis (P-LPS) induced calprotectin release from human neutrophils. P-LPS, a major virulence factor of periodontal pathogens, is known to induce the production and release of inflammatory cytokines through CD14, Toll-like receptor (TLR) and nuclear factor kappaB (NF-kappaB). In the present study, we investigated whether calprotectin release by P-LPS is induced via the CD14-TLR-NF-kappaB pathway and the cellular mechanism of calprotectin release in human neutrophils. MATERIAL AND METHODS: Human neutrophils were isolated from the peripheral blood of healthy donors and pre-incubated in medium containing antibodies against CD14, TLR2 and TLR4, or several inhibitors of NF-kappaB, microtubules and microfilaments, and then incubated with P-LPS. The calprotectin amount in the culture medium was determined using ELISA, and the nuclear extracts from cells were used for the examination of NF-kappaB binding activity using electrophoretic mobility shift assays. RESULTS: P-LPS increased calprotectin release from neutrophils and its induction was inhibited by anti-CD14 and anti-TLR2 antibodies, but not by two anti-TLR4 antibodies. NF-kappaB inhibitors suppressed P-LPS-induced NF-kappaB binding activity and calprotectin release. The inhibitors of microtubule and microfilament polymerization significantly decreased P-LPS-induced calprotectin release. CONCLUSION: These results suggest that calprotectin release is induced by P-LPS via the CD14-TLR2-NF-kappaB signal pathway in human neutrophils and may be dependent on microtubule and microfilament systems.     

Nifedipine induces gingival epithelial hyperplasia in rats through inhibition of apoptosis

BACKGROUND: Nifedipine is used as a long-acting vasodilator; one of its side effects is gingival overgrowth, characterized by an accumulation of collagenous components within the gingival connective tissue and epithelial hyperplasia with elongated, branched rete pegs penetrating into the connective tissue. We investigated the effect of nifedipine on apoptosis of gingival keratinocytes of rats to elucidate the mechanism of nifedipine-induced gingival epithelial hyperplasia. METHODS: Twenty-day-old rats were fed a powdered diet containing or lacking nifedipine for 8 to 30 days. The mandibular gingiva and palatal mucosa were removed on days 8, 15, or 30, and epithelial thickness was examined by light microscopy. In situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was used to examine apoptosis of keratinocytes in the epithelium. In addition, we examined the effects of nifedipine on proliferation of keratinocytes and epithelial cell life on day 8 by 5-bromo-2'-deoxyuridine (BrdU) staining. RESULTS: Microscopic examination showed gingival epithelial hyperplasia in nifedipine-treated rats after day 15. Apoptosis of gingival keratinocytes was seen to be inhibited in nifedipine-treated rats on day 8 and 15. Also, nifedipine did not induce an increase of keratinocyte proliferation activity in terms of the number of cells showing positive staining with BrdU. Prolongation of cell life by nifedipine was observed on day 8 in gingival epithelium through a delay of upward cell movement compared to controls. However, epithelial hyperplasia was not detected in palatal mucosa, and there were no significant differences in apoptotic rates of keratinocytes and cell life between nifedipine-treated rats and control rats. CONCLUSIONS: These results suggest that nifedipine induces epithelial hyperplasia in gingival overgrowth not by an increase in keratinocyte proliferation, but by prolongation of cell life through reduction of apoptosis before epithelial hyperplasia is detectable.     

Abdominal oblique muscle injury at its junction with the thoracolumbar fascia in a high school baseball player presenting with unilateral low back pain

Abdominal oblique muscle injury is characterized by acute pain and localized tenderness over the lateral trunk. This injury is particularly common among throwing athletes, and usually presents as anterolateral abdominal wall pain. Imaging evidence is scarce in regard to whether oblique muscle injury at its junction with the thoracolumbar fascia can instead present with low back pain. A high school baseball player with unilateral low back pain was referred to us with a different diagnosis. Careful palpation and magnetic resonance imaging guided our care, and the patient returned to high-level competition after 7 weeks of conservative treatment, with no report of recurrence in the subsequent 12 months. Oblique muscle injury at its junction with the thoracolumbar fascia should be added to the differential diagnosis for throwing athletes with unilateral low back pain following a torque movement.     

Different patterns of cerebellar abnormality and hypomyelination between POLR3A and POLR3B mutations

Background

Mutations of POLR3A and POLR3B have been reported to cause several allelic hypomyelinating disorders, including hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome). Patients and methods: To clarify the difference in MRI between the two genotypes, we reviewed MRI in three patients with POLR3B mutations, and three with POLR3A mutations. Results: Though small cerebellar hemispheres and vermis are common MRI findings with both types of mutations, MRI in patients with POLR3B mutations revealed smaller cerebellar structures, especially vermis, than those in POLR3A mutations. MRI also showed milder hypomyelination in patients with POLR3B mutations than those with POLR3A mutations, which might explain milder clinical manifestations. Conclusions: MRI findings are distinct between patients with POLR3A and 3B mutations, and can provide important clues for the diagnosis, as these patients sometimes have no clinical symptoms suggesting 4H syndrome.     

Fibrous dysplasia of the maxilla: a case report together with its conventional imaging and dynamic magnetic resonance imaging findings

We previously reported that dynamic contrast-enhanced MRI parameters and time–signal intensity curves (TICs; also known as contrast index curves) are useful for the differential diagnosis of jawbone lesions. In particular, odontogenic fibroma and ossifying fibroma, which possess similar histopathological features (i.e., a mixture of hard and soft tissue components), display unique TIC patterns, and we consider that the TIC patterns of these lesions reflect their hard and soft tissue components. Therefore, fibrous dysplasia, which contains fibrous tissue and immature isolated trabeculae composed of woven bone, is expected to display an interesting TIC. The purpose of this study was to assess the utility of TICs for differentiating between the abovementioned lesions, which have similar histopathological components.     

Metabolic changes in early childhood using LCModel with corrected water scaling method

Purpose:

To examine metabolic changes of the brain in early infancy measured by the LCModel with the water scaling method (LCModel‐WS), and to determine whether the unsuppressed water signal (UWS) on the MR console and the area of the unsuppressed water peak (AUW) in the LCModel can be used to correct metabolite concentrations.

Materials and Methods:

MR spectroscopy was performed on a 1.5 Tesla MR scanner. To determine whether UWS and AUW increases linearly with PD and exp(‐TE/T2), these values were measured using three phantoms with different PD and T2 values. UWS and AUW were also measured (PRESS, TR = 5000 ms, TE = 30 ms, VOI = 4.5 mL) in 57 pediatric controls (aged 2 weeks to 15 years).

Results:

Phantom studies revealed UWS and AUW increases linearly with PD and exp(‐TE/T2). UWS and AUW were high in controls younger than 2 years of age, but gradually decreased to become almost constant after 4 years (UWS = 504 × 10³, AUW = 2.05 × 10⁷). AUW was linearly proportional to UWS in controls. These indicated that metabolite concentrations should be multiplied by the ratio of UWS/504 × 10³ or AUW/2.05 × 10⁷. Age dependent metabolite concentrations corrected by the ratio were obtained.

Conclusion:

Both UWS and AUW can be used to correct metabolite concentrations; these corrections can significantly improve quantification of metabolites' concentration in early childhood. J. Magn. Reson. Imaging 2012;35:174‐180. © 2011 Wiley Periodicals, Inc.