Role of Mel1/Prdm16 in bone differentiation and morphology.

MEL1 (MDS1/EVI1-like gene 1/PRDM16), a zinc finger protein, is located near the chromosomal breakpoint at 1p36 in human acute myeloid leukemia (AML) cells with the t (1; 3) (p36; q21) translocation. Mel1/Prdm16 is not only a causative gene of leukemia, but also has multiple regulatory functions, such as the regulation of fat metabolism. To investigate the function of Mel1/Prdm16, we generated Mel1/Prdm16-deficient mice, but homozygous deficiency (Mel1/Prdm16-/-) was embryonic lethal at E 11.5. Heterozygous mice showed abnormal cartilage and bone formation in the postnatal skull and long bones, suggesting that Mel1/Prdm16 expression plays an important role in bone development. In osteoblast and chondrocyte cell lines, Mel1/Prdm16 promotes the differentiation of chondrocytes and regulates the differentiation of osteoblasts. Transient repression of the master regulator Runx2 is required for chondrocyte differentiation at an early stage of differentiation. However, in Mel1/Prdm16-suppressed ATDC5 cells, the initial suppression of Runx2 was lacking and its expression was upregulated at the beginning of differentiation, suggesting that chondrogenic differentiation is suppressed in Mel1/Prdm16+/- mesenchymal progenitor cells because Runx2 expression is upregulated during the early stage of differentiation. Thus, the Mel1/Prdm16 gene may be involved in the early repression of Runx2 expression during osteochondral differentiation and promote chondrogenic differentiation.

Distribution of hemokinin-1 in the rat trigeminal ganglion and trigeminal sensory nuclear complex.

OBJECTIVE: A new mammalian tachykinin peptide encoded in a TAC4 gene was identified and designated as hemokinin-1 (HK-1). A representative of the tachykinin peptide family is substance P (SP), and the function of SP has been well characterized as a pain transmitter or modulator, while it is possible that HK-1 is involved in pruriceptive processing, but, as yet, the distribution of HK-1 peptide in the trigeminal sensory system is still unknown. Thus, the aim of the present study was to elucidate the distribution of HK-1, while comparing the expression of SP, in the trigeminal ganglion and trigeminal sensory nuclear complex. DESIGN: The trigeminal ganglion and the brain stem of male SD rats were used in the immunohistochemical study. Since the amino acid sequence in the carboxyl-terminal regions of HK-1 and SP is common, polyclonal antibodies of HK-1 and SP derived from 6 amino acids consisting of amino-terminal regions of these peptides were produced in guinea pig and rabbit, respectively. The immunohistochemical staining of HK-1 and SP was conducted using frozen sections of the trigeminal ganglion and brain stem in rats. RESULTS: Immunohistochemical studies revealed the expression of HK-1 in small- and medium-sized trigeminal ganglion neurons, in the paratrigeminal nucleus, and in lamina I of the trigeminal nucleus caudalis, while there was no immunoreactivity of HK-1 in the trigeminal nucleus principalis, trigeminal nucleus oralis, and trigeminal nucleus interpolaris. CONCLUSION: These findings indicate that HK-1 is a target molecule for treatment of itch in the orofaicial regions.

The role of spinal serotonin receptor and alpha adrenoceptor on the antiallodynic effects induced by intrathecal milnacipran in chronic constriction injury rats.

Milnacipran, a reuptake inhibitor of noradrenaline (NA) and serotonin (5-HT), elicits an antiallodynic effect in rats with neuropathic pain; however, the role of NA and 5-HT receptors in the induction of the antiallodynic effect of milnacipran remains unclear. Thus, we examined the effects of prazosin as an α1 adrenoceptor antagonist, yohimbine as an α2 adrenoceptor antagonist, metergoline as a 5-HT1, 5-HT2 and 5-HT7 receptor antagonist, cyanopindolol as a 5-HT1A/1B receptor antagonist, ketanserin as a 5-HT2 receptor antagonist, and ondansetoron as a 5-HT3 receptor antagonist on the antiallodynic effect of milnacipran in neuropathic rats with chronic constriction injury (CCI). The CCI rats expressed mechanical and thermal allodynia, which was attenuated by intrathecal injection of milnacipran. Yohimbine, but not prazosin, reversed the milnacipran-induced antiallodynic effect. The antiallodynic effect of milnacipran was also reversed by metergoline, ketanserin and ondansetron, while cyanopindolol reversed the antiallodynic effect on mechanical, but not thermal stimulation. Furthermore, c-Fos expression in lamina I/II of the spinal dorsal horn was enhanced by thermal stimulation and the enhanced expression of c-Fos was suppressed by milnacipran. This effect of milnacipran was reversed by yohimbine, metergoline, katanserin and ondansetron, but not prazosin. These results indicate that the effect of milnacipran on mechanical and thermal allodynia and c-Fos expression is elicited through the α2 adrenoceptor, but not α1 adrenoceptor, and 5-HT2 and 5-HT3 receptors; furthermore, the 5-HT1A/1B receptor is involved in mechanical allodynia, but not thermal allodynia.

Risk factors for breakage of biodegradable plate systems after bilateral sagittal split mandibular setback surgery.

The aim of this retrospective study was to evaluate the risk factors associated with breakage of biodegradable plate systems after bilateral sagittal split mandibular setback. We studied 169 Japanese adults (62 men, 107 women; age range 16-53 years) with deformities of the jaw diagnosed as mandibular prognathism. All patients were treated by bilateral sagittal split osteotomy (BSSO) with 2 biodegradable fixation plates and screws at the anterior mandibular ramus. We collected the following data from the medical records and radiological findings: sex; age; degree of setback; presence of asymmetry; presence of open bite; operation; design of the plate; operating time; and blood loss. Multiple logistic regression analysis was used to find the factors that were independently associated with the dependent variable: breakage of the biodegradable plate system. In 10 of the 169 patients (6%) the biodegradable plate system for the BSSO broke. Factors that influenced whether or not the biodegradable plate system fractured were if they were asymmetrical (odds ratio (OR) 5.35; P=0.02) and had an open bite (OR 5.20; P=0.02). Asymmetry or open bite was significantly associated with breaks in the biodegradable plate system. Biodegradable plates should be used only when loading is minimal.

Epidermal choristoma arising on the midline gingiva as a congenital epulis: a case report.

We report an extremely rare case of epidermal choristoma in the midline of the maxillary gingiva. A 2-month-old Japanese boy presented with a polypoid mass in the midline of the maxillary gingiva. The initial clinical diagnosis was congenital epulis. Microscopic examination revealed a granular cell layer and melanin pigmentation within the basal cell layer. Furthermore, sebaceous glands and hair follicles were observed within the connective tissue. The histological diagnosis was therefore epidermal choristoma, based on clinical microscopic observations.

Comparison of material-related complications after bilateral sagittal split mandibular setback surgery: biodegradable versus titanium miniplates.

PURPOSE: The aim of the present prospective study was to compare material-related complications using biodegradable and titanium miniplates after bilateral sagittal split mandibular setback surgery. PATIENTS AND METHODS: The subjects included 200 Japanese adults (67 men and 133 women, age range 18 to 45 years) with jaw deformities diagnosed as mandibular prognathism. All patients were prospectively and consecutively randomized to 2 study groups, receiving biodegradable or titanium fixation plates. Of the 200 patients, 110 underwent bilateral sagittal split ramus osteotomy with a biodegradable fixation plate and 90 underwent bilateral sagittal split ramus osteotomy with a titanium metal plate. The clinical records and radiologic findings of the patients were reviewed, and the incidence of material-related complications was compared. RESULTS: The incidence of postoperative complications and breakage in the biodegradable group was 8.2% (9 cases) and in the titanium group was 3.3% (3 cases). No statistically significant difference in the incidence of complications was found between the 2 groups. Fractures of the biodegradable plate occurred at a significantly greater frequency in patients with asymmetry than in patients without asymmetry. CONCLUSION: Biodegradable plates were reliable with minimal material-related complications. However, the use of biodegradable plates should be recommended for minimally loaded situations.

Reduced syndecan-1 expression is correlated with the histological grade of malignancy at the deep invasive front in oral squamous cell carcinoma.

BACKGROUND: Although many histopathological characteristics of oral squamous cell carcinoma (O-SCC) have been identified as prognostic factors, no factor is completely accurate and unequivocal. This study evaluated the association between the loss of syndecan-1 expression and the histological grade of malignancy at the deep invasive front in O-SCC. METHODS: The expression of syndecan-1 at the invasive tumor front of O-SCC was examined immunohistochemically using archived tissue from 72 cases. The mean age of the patients was 62.5 years (range: 23-90 years) and the male-female ratio was 1.3:1 (41 men, 31 women). There were 26, 24, 11, and 11 cases classified as stages I-IV respectively. The correlation between the intensity of syndecan-1 immunostaining and the clinicopathological factors, especially the histological grade of malignancy at the deep invasive front (invasive front grade) was analyzed. RESULTS: Of the 72 cases, seven (9.7%), 29 (40.3%), 36 (50.0%) showed strong, intermediate, and weak or negative syndecan-1 staining respectively. There were significant differences between syndecan-1 expression and prognosis, differentiation, and pattern of invasion at the deep invasive front. Moreover, the invasive front grade scores, based on the intensity of syndecan-1 staining, were 5.6 +/- 1.0, 8.0 +/- 2.1, and 10.2 +/- 2.3 points with strong, intermediate, and weak or negative intensity respectively; and the difference was significant (P < 0.0001). Patients with intermediate or strong intensity for syndecan-1 had significantly better prognoses than did those with negative or weak intensity (P = 0.0138). CONCLUSION: This study demonstrated that the reduced expression of syndecan-1 seems to be a useful marker of histological malignancy at the deep tumor invasive front and may be a useful prognostic factor in O-SCC.

Analysis of muscle hardness in patients with masticatory myofascial pain.

PURPOSE: The aim of the present study was to access any changes in the muscle hardness of the masseter muscle between normal subjects and patients with myofascial pain during brief sustained isometric contractions at various bite force levels, and to compare muscle hardness, especially in terms of the recovery phase, after a clenching task. MATERIALS AND METHODS: Ten patients with masticatory myofascial pain and 10 age- and weight-matched normal healthy controls participated in this study. First, the hardness of the right masseter muscle was measured at the bite force of 0, 3, 6, and 9 kgf with a hand-held hardness meter. Then, the subjects were requested to exert a 9 kgf-clenching task for 30 seconds. The muscle hardness was again measured at 5, 30, and 120 seconds after the task, and the data obtained were compared with the muscle hardness before the clenching task. RESULTS: The results showed that there was no significant difference between the patients and the normal controls, while the muscle hardness increased with contraction in all subjects. The present findings also showed that the patients had a delayed return to baseline after the clenching task compared with the normal subjects, although an immediate increase after the clenching task was seen in all subjects. CONCLUSION: The results indicated that patients with masticatory myofascial pain have different muscle properties in the recovery phase after contraction, probably because of a slower intramuscular reperfusion.

Measurement of muscle hardness using a hardness meter: application to the masseter and temporal muscles and reproducibility of measurement.

This study was designed to evaluate the intra-examiner and inter-examiner reliability of measurements of masticatory muscle hardness and to confirm that the muscle hardness increases with contraction using a commercially available muscle meter. Twenty healthy asymptomatic female subjects participated in this study. Hardness was expressed as numerical relative values (0-100). First, muscle hardness was measured at a standardized point located in the masseter muscle and temporal muscle in a randomized order by two examiners, and again by one of the same examiners after ten minutes for the reproducibility study. Then the muscle hardness was measured at each point for 0 kgf, 3 kgf, 6 kgf, and 9 kgf levels of bite force. As a result, intraclass correlation coefficient (ICC) analysis revealed good intra-examiner reliability in the masseter muscle (ICC = 0.711), good intra-examiner reliability in the temporal muscle (ICC = 0.643), good inter-examiner reliability in the masseter muscle (ICC = 0.631), and unacceptable inter-examiner reliability in the temporal muscle (ICC = 0.008). Also, our results showed that muscle hardness increased with contraction, and relationships with a slope of 1.229, a y-intercept of 62.513, and a correlation coefficient of 0.448 were observed in the masseter muscle. However, no correlation was found between muscle hardness and bite force in the temporal muscle. The findings indicate that measurement of hardness provides reliable physiological information about the masseter muscle in this setting.