The pro-alpha2(XI) collagen gene is expressed in odontoblasts.

Since the dentine is analogous to bone, its extracellular matrix shares many similarities to bone tissues. Similar to the bone, type I collagen is the major organic component in dentine. However, little is known about minor fibrillar collagens, which seem to be co-expressed such as type I or II collagen. The present study examined the gene expression of type V and XI collagens, which play important roles in collagen fibril formation and skeletal morphogenesis, using RT-PCR and in situ hybridization combined with immunohistochemistry. The transcripts of pro-alpha1(XI), pro-alpha2(XI), pro-alpha1(V) and pro-alpha2(V) chains were present, but not pro-alpha3(V) and pro-alpha1(II) chains, of which an overglycosylated variant is pro-alpha3(XI) chain, in mouse incisor tooth, using RT-PCR and in situ hybridization. The pro-alpha2(XI) protein, which is mainly expressed in cartilage, were observed in the odontoblast using a specific polyclonal antibody. Real-time RT-PCR showed that the transcripts of pro-alpha2(XI), pro-alpha1(V) and pro-alpha2(V) were predominant in crown and that of pro-alpha1(XI) in root of the tooth. Finally, the expression of pro-alpha2(XI) was confirmed with an odontoblastic cell line transformed with human telomerase reverse transcriptase (hTERT) both in vitro and in vivo. The data suggest a new subtype of the V/XI collagen molecule containing alpha2(XI) chain.

Genotyping of the cagA gene of Helicobacter pylori on immunohistochemistry with East Asian CagA-specific antibody.

The cytotoxin-associated antigen A (CagA) of Helicobacter pylori prevalent in East Asian countries, where the mortality rate due to gastric cancer is high, has been reported to be structurally different from that in Western countries, where the gastric cancer mortality rate is relatively low. Based on the structural features of the EPIYA motifs located at the carboxyl terminal of the protein, CagA was subdivided into two types: East Asian CagA and Western CagA. A recent study suggested that immunohistochemistry with anti-East Asian-specific antibody (alpha-EAS Ab), which was specifically immunoreactive with East Asian CagA but not with Western CagA, may be useful for diagnosis of the cagA genotype. To further evaluate the value of this diagnostic method in terms of sensitivity, specificity, and accuracy, 143 gastric biopsy specimens with alpha-EAS Ab were analyzed on immunohistochemistry and compared with the sequencing of the cagA gene. It was found that diagnosis of the cagA genotype of H. pylori on immunohistochemistry using the alpha-EAS Ab was highly sensitive (sensitivity 93.2%) and specific (specificity 72.7%), suggesting that immunohistochemical diagnosis of the cagA genotype is useful for diagnosis of the cagA genotype.

The number of microvascular complications is associated with an increased risk for severity of periodontitis in type 2 diabetes patients: Results of a multicenter hospital-based cross-sectional study.

AIMS/INTRODUCTION: To explore the relationships between periodontitis and microvascular complications as well as glycemic control in type 2 diabetes patients. MATERIALS AND METHODS: This multicenter, hospital-based, cross-sectional study included 620 patients with type 2 diabetes. We compared the prevalence and severity of periodontitis between patients with ≥1 microvascular complication and those without microvascular complications. We also compared the prevalence and severity of periodontitis among patients with different degrees of glycemic control. RESULTS: After adjusting for confounding factors, multiple logistic regression analysis showed that the severity of periodontitis was significantly associated with the number of microvascular complications (odds ratio 1.3, 95% confidence interval 1.1-1.6), glycated hemoglobin ≥8.0% (64 mmol/mol; odds ratio 1.6; 95% confidence interval 1.1-2.3), and older age (≥50 years; odds ratio 1.7; 95% confidence interval 1.1-2.6). However, the prevalence of periodontitis was not significantly associated with the number of microvascular complications, but was associated with male sex, high glycated hemoglobin (≥8.0% [64 mmol/mol]), older age (≥40 years), longer duration of diabetes (≥15 years) and fewer teeth (≤25). Furthermore, propensity score matching for age, sex, diabetes duration and glycated hemoglobin showed that the incidence of severe periodontitis was significantly higher among patients with microvascular complications than among those without microvascular complications (P < 0.05). CONCLUSIONS: The number of microvascular complications is a risk factor for more severe periodontitis in patients with type 2 diabetes, whereas poor glycemic control is a risk factor for increased prevalence and severity of periodontitis.

Pro-alpha3(V) collagen chain is expressed in bone and its basic N-terminal peptide adheres to osteosarcoma cells.

The third alpha-chain of type V collagen, alpha3(V) chain, was initially identified in the placenta more than 20 years ago, but was poorly characterized with regard to its expression and function. We generated a specific monoclonal antibody against the N-terminal domain of the pro-alpha3(V) chain and examined gene expression using immunohistochemical methods combined with in situ hybridization. The pro-alpha3(V) chain was seen in funis and amnion, but not chorionic villi and deciduas of mouse placenta. In mouse embryo, the transcripts of the pro-alpha3(V) gene were seen in tissues that were related to bone formation as well as developing muscle and nascent ligament previously reported. However, immunohistochemistry showed that pro-alpha3(V) protein accumulated rather in the developing bone of mouse embryo. On the other hand, the N-terminal globular domain of the pro-alpha3(V) chain has a unique structure that contains a highly basic segment of 23 amino acids. The peptide derived from the basic segment showed a specific adhesive feature to osteosarcoma cells but not to chondrosarcoma cells. The four heparin binding sites in the basic segment equally contribute toward adhesion to the osteosarcoma cells. Our data suggested that N-terminal globular domain of the pro-alpha3(V) chain influence bone formation of osteoblasts through proteoglycan on the cell surface during development or regeneration.

Necessity of screening for multiple primary cancers in patients with esophageal cancer.

This study divided patients with esophageal cancer and multiple primary cancers into two groups, a head and neck cancer (HNC) group and a non-head and neck cancer (NHNC) group. These groups were then evaluated on the basis of clinical and pathological studies. Among 92 patients with esophageal cancer as one of multiple primary cancers, 38 (41.8%) were assigned to the HNC group. The following characteristics distinguished patients in the HNC group from those in the NHNC group: (1) younger age; (2) shorter interval between diagnosis of metachronous cancers; (3) many displayed superficial esophageal cancer. Among the cases in which esophageal cancer was discovered synchronously with head and neck cancer, head and neck cancers were discovered before esophageal cancer; and (4) many patients displayed esophageal dysplasia, and many had multiple esophageal cancers. In the present study, we demonstrated the necessity of screening for multiple primary cancers in patients with esophageal cancer.

Topographic study on nerve-associated lymphatic vessels in the murine craniofacial region by immunohistochemistry and electron microscopy.

The distribution and fine structure of lymphatic vessels associated with nerves was studied by immunohistochemistry in the murine craniofacial region. The tissue sections and blocks were immunostained for LYVE-1, protein gene product 9.5, CD34 and aquaporin-1 to demonstrate the lymphatic vessels, nerves, blood vessels and water channel protein, respectively. Transmission electron microscopic examination was also performed to investigate the relationship between the lymphatics and nerves. In the nasal area, the lymphatics were found in dura mater on the cribriform plate and beneath the nasal mucosa, this supposedly supplying the cerebrospinal fluid drainage route along the olfactory nerves. The proximal portions of the cranial nerves were equipped with the lymphatics in the epineurium. In the distal portions of the nerves, the lymphatics were distributed in close proximity of the perineural sheath, and thus might contribute to maintenance of microenvironment suitable for the nerves by an absorptive activity of the lymphatic endothelial cells. The present findings suggest that the lymphatic system associated with the cranial nerves provides the pathway for transport of cerebrospinal fluid, tissue fluid, and free cells involved in immune response and tumor metastasis in the craniofacial region.

Malignant calcifying epithelial odontogenic tumor of the mandible: report of a case with pulmonary metastasis showing remarkable response to platinum derivatives.

We describe a case of CEOT of the mandible, which underwent malignant transformation and developed metastatic tumors of the lung after repeated local recurrence. The primary tumor revealed typical histological features of benign CEOT showing sheets of polyhedral epithelial cells associated with abundant eosinophilic amyloid-like materials. On the other hand, the locally recurrent tumors had malignant features, such as increased nuclear pleomorphism with frequent mitotic figures and vascular invasion of tumor cells, as well as increased proliferative activity assessed by immunostaining for Ki-67. Chemotherapy was carried out against the pulmonary metastatic lesions, which showed a drastic response after 3 courses of intravenous administration of cisplatin (CDDP). To date, a total of 6 courses of CDDP and 6 courses of nedaplatin (CDGP) have been done, and the remaining pulmonary tumors have been dormant. This suggests that platinum derivatives could be a chemotherapeutic agent of choice against this rare tumor.

Predictive value of laminin-5 and membrane type 1-matrix metalloproteinase expression for cervical lymph node metastasis in T1 and T2 squamous cell carcinomas of the tongue and floor of the mouth.

BACKGROUND: Laminin-5 (Ln-5) cleaved by membrane type 1-matrix metalloproteinase (MT1-MMP) enhances the migration of tumor cells. The purpose of this study was to determine whether or not enhanced expression of both Ln-5 and MT1-MMP was associated with lymph node metastasis in patients with T1 and T2 squamous cell carcinoma (SCC) of the tongue and floor of the mouth. METHODS: By use of biopsy specimens of primary tumors from 57 patients, intratumoral expression of Ln-5 and MT1-MMP was evaluated immunohistochemically and its association with node metastasis analyzed. RESULTS: The tumors were categorized into three groups: Ln-5 focal type/MT1-MMP (-) (group I, n = 14), Ln-5 focal type/ MT1-MMP (+) and Ln-5 diffuse type/MT1-MMP (-) (group II, n = 16), and Ln-5 diffuse type/MT1-MMP (+) (group III, n = 27). The incidence of node metastasis (initial and latent metastases) was two of 14 (14.3%), five of 16 (31.3%), and 15 of 27 (55.6%) in groups I, II, and III, respectively. Multivariate analysis identified tumor thickness (odds ratio, 4.751; p = .0152) and Ln-5/ MT1-MMP expression (odds ratio, 3.795, p = .0304) as independent factors of node metastasis. Moreover, in 35 patients with N0 disease, Ln-5/MT1-MMP expression was the only parameter associated with latent node metastasis (odds ratio, 12.800, p = .0247). CONCLUSION: These results suggest that immunohistochemical evaluation of Ln-5 and MT1-MMP expression is useful for identifying patients with T1 and T2 SCC of the tongue and floor of the mouth who should be treated with elective neck dissection.

Primary neck management among patients with cancer of the oral cavity without clinical nodal metastases: A decision and sensitivity analysis.

BACKGROUND: A standardized neck management strategy for oral cancer patients without clinical nodal metastases remains to be established. Consequently, a decision and sensitivity analysis of two neck management protocols, involving either prophylactic neck dissection or careful observation, was conducted using the Oral Cancer Registry of Kyushu, Japan. METHODS: We calculated probabilities of subclinical nodal metastases and 5-year survival using the registry data. A two-way sensitive analysis was conducted using the probabilities and parameters of the complete nodal metastasis resection rate (x) and a utility rating that describes the health state induced by dissection (y) compared with the neck condition in a careful-observation group. RESULTS: We solved the threshold curve for y and x for the expected utility between the two groups. The results showed that prophylactic neck dissection must guarantee a complete resection of subclinical nodal metastases with no disadvantage to health state to be evaluated as equally satisfactory as careful observation. CONCLUSIONS: Careful observation involving standardized systematic preoperative and postoperative screening of the neck seems preferable to prophylactic neck dissection for oral cancer patients without subclinical nodal metastases.