Keloids tend to occur on highly mobile sites with high tension. This study was designed to determine whether body surface areas exposed to large strain during normal activities correlate with areas that show high rates of keloid generation after wounding. Eight adult Japanese volunteers were enrolled to study the skin stretching/contraction rates of nine different body sites. Skin stretching/contraction was measured by marking eight points on each region and measuring the change in location of the marked points after typical movements. The distribution of 1,500 keloids on 483 Japanese patients was mapped. The parietal region and anterior lower leg were associated with the least stretching/contraction, while the suprapubic region had the highest stretching/contraction rate. With regard to keloid distribution, there were 733 on the anterior chest region (48.9%) and 403 on the scapular regions (26.9%). No keloids were reported on the scalp or anterior lower leg. Because these sites are rarely subjected to skin stretching/contraction, it appears that mechanical force is an important trigger that drives keloid generation even in patients who are genetically predisposed to keloids. Thus, mechanotransduction studies are useful for developing clinical approaches that reduce the skin tension around wounds or scars for the prevention and treatment of not only keloids but also hypertrophic scars.

The O-glycan branching enzyme, core2 b-1,6-N-acetylglucosaminyltransferase (C2GnT), forms O-glycans containing an N-acetylglucosamine branch connected to N-acetylgalactosamine (core2 O-glycans) on cell-surface glycoproteins. Here, we report that upregulation of C2GnT is closely correlated with progression of bladder tumours and that C2GnT-expressing bladder tumours use a novel strategy to increase their metastatic potential. Our results showed that C2GnT-expressing bladder tumour cells are highly metastatic due to their high ability to evade NK cell immunity and revealed the molecular mechanism of the immune evasion by C2GnT expression. Engagement of an NK-activating receptor, NKG2D, by its tumour-associated ligand, Major histocompatibility complex class I-related chain A (MICA), is critical to tumour rejection by NK cells. In C2GnT-expressing bladder tumour cells, poly-N-acetyllactosamine was present on core2 O-glycans on MICA, and galectin-3 bound the NKG2D-binding site of MICA through this poly-N-acetyllactosamine. Galectin-3 reduced the affinity of MICA for NKG2D, thereby severely impairing NK cell activation and silencing the NK cells. This new mode of NK cell silencing promotes immune evasion of C2GnT-expressing bladder tumour cells, resulting in tumour metastasis.

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Abstract-Tumor-necrosis factor-␣ (TNF-␣) is a proinflammatory cytokine with a wide variety of biological effects. The most important source of this cytokine is monocytes/macrophages. It is a potent agonist in the activation of endothelial cells; however, the precise role of endothelial cells as a source of TNF-␣ is not known. In the present study, we addressed the possibility that TNF-␣ is produced by cultured human umbilical vein endothelial cells (

The isolation and sequencing of a cDNA clone coding for the entire sequence of pig thymus non-histone protein HMG1 are described. The sequence analysis reveals a complete 2192-nucleotide sequence with a 5'-terminal untranslated region of 11 nucleotides, 642 nucleotides of an open reading frame that encoded 214 amino acids, and a 3'-terminal untranslated region of 1539 nucleotides. The HMG1 protein, deduced from the nucleotide sequence, has a molecular weight of 24,785 and a C-terminal of a continuous run of 30 acidic amino acids, encoded by a simple repeating sequence of (GAN)30. The predicted amino acid sequence is homologous to HMG1, HMG2, and HMG-T sequences from several sources, suggesting that the protein conformation is under evolutionary constraints. Northern blot analysis reveals that another hybridizable RNA species of smaller size is present. Southern blot analyses suggest that pig genome contains several HMG1 gene equivalents.