Platelets play an important role in hemostasis, thrombosis, and antimicrobial host defense and are also involved in the induction of inflammation, tissue repair, and tumor metastasis. We have previously characterized the platelet aggregation-inducing sialoglycoprotein (Aggrus/gp44) overexpressed on the surface of tumor cells. Because a platelet aggregation-neutralizing 8F11 monoclonal antibody that could specifically recognize Aggrus suppressed tumor-induced platelet aggregation, we have previously purified Aggrus by 8F11-affinity chromatography and found that purified Aggrus possessed the ability to induce aggregation of platelets. Here we show that Aggrus is identical to the T1␣/gp38P/ OTS-8 antigen, the function of which in tumors is unknown. Expression of mouse Aggrus and its human homologue (also known as T1␣-2/gp36) induced platelet aggregation without requiring plasma components. Using the 8F11 antibody, we identified the highly conserved platelet aggregation-stimulating domain with putative O-glycosylated threonine residues as the critical determinant for exhibiting platelet aggregation-inducing capabilities. We compared the expression level of human aggrus mRNA using an array containing 160 cDNA pair samples derived from multiple human tumorigenic and corresponding normal tissues from individual patients. We found that expression level of aggrus was enhanced in most colorectal tumor patients. To confirm the protein expression, we generated anti-human Aggrus polyclonal antibodies. Immunohistochemical analysis revealed that Aggrus expression was frequently up-regulated in colorectal tumors. These results suggest that Aggrus/T1␣ is a newly identified, platelet aggregation-inducing factor expressed in colorectal tumors.Specific glycoproteins expressed on the surface of platelets enable the platelets to adhere to receptors exposed in areas of vascular damage (1). The process of adhesion activates platelet aggregation, leading to the formation of a platelet plug in the vessel wall. Activated platelets also induce the formation of a fibrin clot by carrying coagulation factors and providing a catalytic surface for the major interactions of the coagulation cascade. Because there exists a clear link between atherosclerotic vascular disease, inflammation, tumor metastasis, and thrombosis (1-3), it is important to identify the mechanisms of platelet aggregation that have pathobiologic, prognostic, and treatment-related relevance. Studies on cancer metastasis have shown that some human and animal tumor cells possess platelet aggregation-inducing abilities that correlate with their metastatic potential (2, 3). Interactions between tumor cells and platelets have been considered to facilitate the arrest of tumor cell cluster in the microcirculation with the subsequent formation of experimental metastasis. However, the molecules associated with the tumor-induced platelet aggregation have not yet been identified.We previously established several clones possessing different platelet aggregation-inducing capabilities from ...

No abstract

Shovel shape of upper incisors is a common characteristic in Asian and Native American populations but is rare or absent in African and European populations. Like other common dental traits, genetic polymorphisms involved in the tooth shoveling have not yet been clarified. In ectodysplasin A receptor (EDAR), where dysfunctional mutations cause hypohidrotic ectodermal dysplasia, there is a nonsynonymous-derived variant, 1540C (rs3827760), that has a geographic distribution similar to that of the tooth shoveling. This allele has been recently reported to be associated with Asian-specific hair thickness. We aimed to clarify whether EDAR 1540C is also associated with dental morphology. For this purpose, we measured crown diameters and tooth-shoveling grades and analyzed the correlations between the dental traits and EDAR genotypes in two Japanese populations, inhabitants around Tokyo and in Sakishima Islands. The number of EDAR 1540C alleles in an individual was strongly correlated with the tooth-shoveling grade (p = 7.7 x 10(-10)). The effect of the allele was additive and explained 18.9% of the total variance in the shoveling grade, which corresponds to about one-fourth of the heritability of the trait reported previously. For data reduction of individual-level metric data, we applied a principal-component analysis, which yielded PC1-4, corresponding to four patterns of tooth size; this result implies that multiple factors are involved in dental morphology. The 1540C allele also significantly affected PC1 (p = 4.9 x 10(-3)), which denotes overall tooth size, and PC2 (p = 2.6 x 10(-3)), which denotes the ratio of mesiodistal diameter to buccolingual diameter.

The aim of this study was to develop a simple method using universal primers for species identification based on direct PCR sequencing. Two primer sets were designed based on the conserved regions of the 12S and 16S rRNA loci detected by the comprehensive sequence comparison among 30 mammalian whole mitochondrial genomes. In humans, the expected sizes of PCR products of the 12S and 16S rRNAs were 215 and 244 bp, respectively. Both primer sets successfully amplified the expected PCR products from various kinds of vertebrates including mammals, birds, reptiles, amphibians, and fish, and the sequenced segments contained sufficient nucleotide differences to identify each animal species. A case example of the identification of a piece of buried bone of unknown species is presented, and the species was identified as a pig by this method.

Aggrus (T1α/podoplanin, known as a specific marker for type I alveolar cells or lymphatic endothelial cells) is a transmembrane sialoglycoprotein that aggregates platelets. Previously, we showed that upregulated expression of Aggrus occurs in colorectal tumors or testicular tumors and could be associated with platelet-aggregating activity and metastatic ability. In testicular tumors, Aggrus is specifically expressed in seminoma. The present study investigates Aggrus expression in human primary lung cancer tissues of different types. Microarray analysis demonstrated that aggrus was significantly expressed in squamous cell carcinoma (10/15; 66.7%). Immunohistochemical analysis also showed that the incidence of positive staining in sections of squamous cell carcinoma (7/8; 87.5%) was higher than that in adenocarcinoma (2/13; 15.4%). Furthermore, Aggrus expression was detected in a squamous cell carcinoma cell line, NCI-H226, by real-time PCR. These findings indicated that overexpression of Aggrus occurred in squamous cell carcinoma of the lung. Therefore, Aggrus could be a useful diagnostic marker for squamous cell carcinoma of the lung.