Perforation of the temporomandibular joint disc: cadaveric anatomical study.

The aim of this human cadaveric study was to investigate the relationship between temporomandibular joint disc perforation and bony changes of the mandibular condyle. Overall, 135 cadaveric mandibles were used (69 male, 66 female; all White). Mean age at death was 78.7 years. Perforation of the disc was investigated. Differences in the area of the perforation according to the different types of bony change (erosion, flattening, osteophyte) were evaluated. Perforation of the disc was observed in 34.8% of all mandibles, occurring unilaterally in 53.2% of cases and bilaterally in 46.8%. The prevalence of perforation was 16.4% in cadavers <80 years old (67 heads) and 52.9% in those ≥80 years old (68 heads) (P < 0.001). Osteophyte formation was always identified along with other bony changes (21.7%) and never in isolation. The area of the perforation was significantly larger in the groups with bony changes (one, two, or three changes) than in the 'no bony change' group. The group with osteophyte formation showed a significantly larger perforated area than the group without osteophyte formation; likewise, the group with flattening showed a significantly larger perforated area than the group without flattening. Osteophytes and flattening are probably secondary bony changes that occur following disc perforation. Based on this study, disc perforation should be suspected when these findings are identified on imaging.

Neural network application in Japanese sign language: distinction of similar Yubimoji gestures.

In a previous paper, the authors built a neural network model to recognize Japanese sign language syllabary or yubimoji. One of the problems encountered in that study was the accurate digital representation and distinction of similar yubimoji gestures, i.e. gestures with the same finger flexure positions but with different hand/finger orientations. This study focuses on these yubimoji gestures. Using data from a glove interface with bend sensors and accelerometers, a neural network was built, trained and tested. The network performed well and good results were obtained.

Variability in organ-specific EGFR mutational spectra in tumour epithelium and stroma may be the biological basis for differential responses to tyrosine kinase inhibitors.

Organ-specific differences in epidermal growth factor receptor (EGFR) mutational spectra and frequencies were found in lung cancer and sporadic and BRCA1/2-related breast cancers. Additionally, we found a high frequency of EGFR mutations in the tumour stroma of these invasive breast carcinomas. Those organ-specific mutational spectra and potential targets in the cancer-associated stroma might influence the efficacy of TKI therapy.

Cortical dysplasia with subcutaneous angioma and dilated dural venous sinuses.

We report a rare case with dilated dural venous sinuses, cortical dysplasia, and a subcutaneous angioma in the forehead. These lesions may be derived from some factors in the certain period of gestation, during which dural venous sinuses dilate due to increased intracranial pool of blood.

The c-Jun NH2-terminal kinase3 (JNK3) gene: genomic structure, chromosomal assignment, and loss of expression in brain tumors.

By examining 19 human cell lines derived from brain tumors for altered expression of expressed sequence tags (ESTs) in chromosomal band 4q21-22, we detected loss of expression, in 10 cell lines, of two sequences, WI6336 and WI7913. Both corresponded to the c-Jun NH2-terminal kinase (JNK) 3. In the present study, genomic cloning revealed that the JNK3 gene consists of 14 exons interrupted by 13 introns; its transcription-initiation site is within exon 3 and the termination codon lies in exon 14. Fluorescence in situ hybridization (FISH) and radiation-hybrid mapping confirmed the gene to 4q21-22. Together with prior evidence that, in JNK3-deficient mice, the JNK3 signaling pathway mediates apoptosis in central nervous tissue, our results suggest that loss of expression of the JNK3 gene may play an important role in the development of brain tumors in humans.

Detection of Epstein-Barr virus DNA and expression of CD30 antigen in primary anaplastic diffuse large B-cell lymphoma of the brain.

We describe a case of primary anaplastic diffuse large-cell lymphoma arising in the central nervous system (CNS). Primary CD30-positive anaplastic diffuse large B-cell lymphoma of the brain is very rarely reported. Given that this tumor is immunohistochemically heterogeneous, polymerase chain reaction (PCR) and Epstein-Barr virus (EBV) analysis of tumor DNA are essential techniques for early and accurate histological diagnosis in these CD30-positive cerebral lymphoma cases. We report an early CD30- and EBV-positive anaplastic diffuse large B-cell lymphoma in the CNS that was diagnosed not only from the immunohistochemical study and MRI findings, but also from the genotype confirmations. This tumor was documented to have EBV episomes of monoclonal origin by PCR analysis of immunoglobulin gene rearrangement.

A mouse model of vascular injury that induces rapid onset of medial cell apoptosis followed by reproducible neointimal hyperplasia.

Genetically modified mice serve as a powerful tool to determine the role of specific molecules in a wide variety of biological phenomena including vascular remodeling. Several models of arterial injury have been proposed to analyze transgenic/knock-out mice, but many questions have been raised about their reproducibility and physiological significance. Here, we report a new mouse model of vascular injury that resembles balloon-angioplasty. A straight spring wire was inserted into the femoral artery via arterioctomy in a small muscular branch. The wire was left in place for one minute to denude and dilate the artery. After the wire was removed, the muscular branch was tied off and the blood flow of the femoral artery was restored. The lumen was enlarged with rapid onset of medial cell apoptosis. While the circumference of the external elastic lamina remained enlarged, the lumen was gradually narrowed by neointimal hyperplasia composed of smooth muscle cells. At 4 weeks, a concentric and homogeneous neointimal lesion was formed reproducibly in the region where the wire had been inserted. Similar exuberant hyperplasia could be induced in all strains examined (C57BL/6J, C3H/HeJ, BALB/c, and 129/SVj). This model may be widely used to study the molecular mechanism of post-angioplasty restenosis at the genetic level.

A family with hydrocephalus as a complication of cerebellar hemangioblastoma: identification of Pro157Leu mutation in the VHL gene.

Various mutations in the VHL gene on chromosome 3p25-26 are responsible for von Hippel-Lindau (VHL) syndrome. We report on a Japanese VHL family in which two of the three affected members developed acute occlusive hydrocephalus that necessitated emergency surgery for ventricular shunt or drainage. Direct sequencing and restriction fragment length polymorphism analysis identified a germline missense mutation, Proline-to-Leucine, caused by a C-to-T transition at the second nucleotide of codon 157.

Allelic loss at 1p34, 13q12, 17p13.3, and 17q21.1 correlates with poor postoperative prognosis in breast cancer.

Allelic losses of tumor suppressor genes (TSGs), or the chromosomal regions harboring them, in tumor DNA may become useful postoperative prognostic indicators. To examine whether specific allelic losses might correlate with postoperative survival in a 5-year prospective follow-up, we tested tumors from a cohort of 264 breast cancer patients for allelic losses of 18 microsatellite markers representing either a known TSG or a region where genetic alterations are frequent in breast tumors. Patients whose tumors had lost an allele at 1p34, 13q12, 17p13.3, or 17q21.1 had significantly higher risks of postoperative mortality than those whose tumors retained both alleles at those loci (at 1p34, a 5-year mortality rate of 29% among patients with losses vs. 7% with retentions, P = 0. 0008; at 13q12, 31% vs. 10%, P = 0.0062; at 17p13.3, 24% vs. 13%, P = 0.026; and at 17q21.1, 31% vs. 13%, P = 0.0047). Furthermore, combined losses at 13q12 and 17p13.3 increased the predicted postoperative mortality risks by a factor of 9.6 (5-year mortality rate of 42% vs. 5% with retentions, P = 0.0001), and combined losses at 1p34 and 17p13.3 raised the predicted postoperative mortality risks by a factor of 8.6 (27% vs. 3%, P = 0.0064). We conclude that allelic losses at these loci can serve as negative prognostic indicators to guide postoperative management of patients. Genes Chromosomes Cancer 26:134-141, 1999.

Somatic mutation of the PTEN/MMAC1 gene in breast cancers with microsatellite instability.

The extent to which microsatellite instability (MI) contributes to the etiology of breast cancer has not been established in any large-scale studies. We examined 528 samples of tumor DNA from patients with primary breast cancer for MI, using 14 polymorphic CA-repeat markers. The frequency of MI in these tumors was unexpectedly low (10/528, 1.9%). The ten MI+ tumors were analyzed for mutations in five potential target genes that contain simple repeat sequences (TGFBIIR, IGF2R, hMSH6, BAX and PTEN/MMAC1). A somatic insertion of an extra adenine in the (A)6 region at codon 321-323 (exon 8) of the PTEN/MMAC1 gene, leading to a frame-shift, was identified in one tumor. This observation represented the first documented instance of PTEN/MMAC1 alteration in a MI+ primary breast cancer.

Analysis of the MEN1 gene in sporadic pituitary adenomas from Japanese patients.

An autosomal-dominant syndrome known as multiple endocrine neoplasia type 1 (MEN1) is characterized by tumors in parathyroid glands, pancreatic endocrine tissues and the anterior pituitary gland. The predisposing gene was identified at 11q13 when germline mutations in the MEN1 gene were detected in affected pedigrees. To investigate a possible role of this gene in tumorigenesis of non-familial pituitary adenomas, we examined 24 sporadic tumors from Japanese patients for loss of heterozygosity (LOH) at the 11q13 region and for somatic mutations in the entire coding region and exon-intron boundaries of MEN1. Although three common sequence variants were detected, none of the tumors exhibited either LOH or somatic mutations of this gene. Our results indicate that inherited and sporadic forms of pituitary adenomas are different in terms of the genetic events that contribute to their development, and that other loci associated with pituitary neoplasia must still be sought.

Frequent allelic loss at the TOC locus on 17q25.1 in primary breast cancers.

Sporadic breast cancers often show allelic losses on the long arm of chromosome 17. Since the BRCA1 gene lies at 17q21.1 and the TOC locus, associated with esophageal cancer, lies at 17q25.1, either gene could be the target of those losses. We examined both loci in 178 primary breast cancers, using microsatellite markers covering the relevant regions of 17q, and observed allelic losses in 97 tumors (55%). Losses were most frequent at markers around the TOC locus (48% at D7S1839 and 43% at D17S1603), where we identified a distinct commonly deleted region within a I -cM interval. Another larger, separate commonly deleted region including the BRCA1 gene was also identified, which exhibited 45% of allelic loss (at D17S934). Allelic loss on 17q was more frequent in tumors of the solid-tubular histologic type (P = 0.0129) and in estrogen-negative and progesterone-negative tumors (P = 0.0281 and 0.0196, respectively). The results indicated that BRCA1 and TOC are independent targets of allelic loss on 17q in primary breast cancers, and that inactivation of the TOC locus in particular may play an important role in the genesis of sporadic breast tumors.

Somatic mutations of the PTEN/MMAC1 gene in fifteen Japanese endometrial cancers: evidence for inactivation of both alleles.

Loss of heterozygosity (LOH) of chromosome 10q is observed in approximately 40% of endometrial cancers. Mutations in PTEN/MMAC1, a gene recently isolated from the 10q23 region, are responsible for two dominantly inherited neoplastic syndromes, Cowden disease and Bannayan-Zonana syndrome. Somatic mutations of this gene have also been detected in sporadic cancers of the brain, prostate and breast. To investigate the potential role of this putative tumor suppressor gene in endometrial carcinogenesis as well, we examined 46 primary endometrial cancers for LOH at the 10q23 region, and for mutations in the entire coding region and exon-intron boundaries of the PTEN/MMAC1 gene. LOH was identified in half of the 38 informative cases, and subtle somatic mutations were detected in 15 tumors (33%). Our results suggest that of the genes studied so far in endometrial carcinomas, PTEN/MMAC1 is the most commonly mutated one, and that inactivation of both copies by allelic loss and/or mutation, a pattern that defines genes as "tumor suppressors," contributes to tumorigenesis in endometrial cancers.