Regional differences in D/L aspartic acid ratios in the human mandible as a possible indicator of the bone remodeling rate

In slowly metabolizing tissue such as tooth, bone and ocular lens, D-amino acids converted from L-amino acids accumulate with age and thus reflect the tissue turnover rate. To investigate whether D-amino acids play a role in determining the bone remodeling rate, we measured the accumulation of D-aspartic acid, which has the fastest rate of racemization, in various areas of the mandible. The level of D-aspartic acid was higher in the ramus than in the body (P < 0.01), and within the body, the level was higher in the basal area than in the alveolar area (P < 0.01). Within the alveolar area, the level of D-aspartic acid was higher in the molar region than in the incisal region (P: 0.05-0.01). No correlation was found between the accumulated level of D-aspartic acid with age, because all the specimens were obtained from elderly people with only a few years difference in age. There was also no correlation between D-aspartic acid and sex. In conclusion, we suggest that accumulation of D-aspartic acid in the mandibular bone reflects the differences in remodeling associated with occlusion. The incisal portion of the alveolar area of the mandible (above the mandibular canal), shows the greatest evidence of active remodeling.     

Familial Non-Medullary Thyroid Carcinoma: An Update

Familial thyroid cancer can arise from follicular cells (familial non-medullary thyroid carcinoma (FNMTC)) or from the calcitonin-producing C-cell (familial medullary thyroid carcinoma). This is usually a component of multiple endocrine neoplasias (MEN) IIA or IIB, or as pure familial medullary thyroid carcinoma syndrome. The genetic events in the familial C-cell-derived tumors are known and genotype–phenotype correlations are well established. In contrast, the case for a familial predisposition of non-medullary thyroid carcinoma is only now beginning to emerge. Although the majority of papillary (PTC) and follicular thyroid carcinomas (FTC) are sporadic, familial tumors account for over 5% of cases. The presence of multifocal papillary carcinoma is a common feature of FNMTC. The familial follicular cell-derived tumors or non-medullary thyroid carcinomas encompass a heterogeneous group of diseases, including diverse syndromic-associated tumors and non-syndromic tumors. Based on clinico-pathologic findings, FNMTC is divided into two groups. The first includes familial syndromes characterized by a predominance of non-thyroidal tumors, such as familial adenomatous polyposis (FAP), PTEN hamartoma tumor syndrome (PHTS), Carney complex type 1, and Werner syndrome. The second group includes familial syndromes characterized by a predominance of NMTC, such as pure familial (f) PTC with or without oxyphilia, fPTC with papillary renal cell carcinoma, and fPTC with multinodular goiter. Some characteristic morphologic findings should alert the pathologist of a possible familial cancer syndrome, which may lead to further molecular genetic evaluation.     

Roles of a prostaglandin E-type receptor, EP3, in upregulation of matrix metalloproteinase-9 and vascular endothelial growth factor during enhancement of tumor metastasis

Cyclooxygenase (COX)-2 is known to correlate with poor cancer prognosis and to contribute to tumor metastasis. However, the precise mechanism of this phenomenon remains unknown. We have previously reported that host stromal prostaglandin E₂ (PGE₂)–prostaglandin E2 receptor (EP)3 signaling appears critical for tumor-associated angiogenesis and tumor growth. Here we tested whether the EP3 receptor has a critical role in tumor metastasis. Lewis lung carcinoma (LLC) cells were intravenously injected into WT mice and mice treated with the COX-2 inhibitor NS-398. The nonselective COX inhibitor aspirin reduced lung metastasis, but the COX-1 inhibitor SC560 did not. The expression of matrix metalloproteinases (MMP)-9 and vascular endothelial growth factor (VEGF)-A was suppressed in NS-398-treated mice compared with PBS-treated mice. Lungs containing LLC colonies were markedly reduced in EP3 receptor knockout (EP3^−/−) mice compared with WT mice. The expression of MMP-9 and VEGF-A was downregulated in metastatic lungs of EP3^−/− mice. An immunohistochemical study revealed that MMP-9-expressing endothelial cells were markedly reduced in EP3^−/− mice compared with WT mice. When HUVEC were treated with agonists for EP1, EP2, EP3, or EP4, only the EP3 agonist enhanced MMP-9 expression. These results suggested that EP3 receptor signaling on endothelial cells is essential for the MMP-9 upregulation that enhances tumor metastasis and angiogenesis. An EP3 receptor antagonist may be useful to protect against tumor metastasis. ( Cancer Sci 2009; 100: 2318–2324)     

Predictive factors for overall and progression-free survival,and dissemination in oligodendroglial tumors

The pattern of recurrence and predictive factors for tumor progression, dissemination and survival in oligodendroglial tumors were investigated. 56 consecutive patients with oligodendroglial tumors were retrospectively analyzed to determine the predictive significance of various factors, including World Health Organization grade, loss of chromosomes 1p and 19q, and immunohistochemical features of TP53, O⁶-methylguanine-deoxyribonucleic-acid-methyltransferase, CD44H, nestin, and Ki-67. Eleven patients developed dissemination, and had significantly shorter post-progression survival compared to ten patients with local recurrence. Univariate analysis showed that retention of chromosome 1p or 19q, Ki-67 labeling index ≥ 25%, diffuse expression of nestin, and p53 labeling index ≥ 10% were unfavorable factors for overall, progression-free, and dissemination-free survival. Multivariate analysis showed that Ki-67 labeling index ≥ 25% and diffuse expression of nestin were significant for dissemination-free survival. In conclusion, post-progression survival shows significant differences between patients with local and disseminated recurrence. Ki-67 labeling index and nestin expression pattern are useful markers to predict dissemination.     

Lobular phenotype related to occult-metastatic spread in axillary sentinel node and/or bone marrow in breast carcinoma

To determine whether any histological trait was associated with regional and/or systemic spread of occult tumour cells (OTCs) in small size invasive breast cancer, we compared tumour characteristics, axillary sentinel lymph node (SN) and bone marrow (BM) status in a series of 287 pT1T2 cases.Surgery was the first step of treatment, associated with SN procedure and with BM aspiration for the detection of OTC. SN was histologically classified as negative, metastatic (>2 mm), micro-metastatic (>0.2 mm and ?2 mm) or involved by OTC detected by immunohistochemistry (Ni+, ?0.2 mm). BM specimens were analysed after immunocytochemistry and classified as negative or positive with atypical cytokeratin-positive OTC.Metastasis and micro-metastasis in the SN were correlated with size, grade and vascular invasion. In contrast, presence of OTC in both SN and BM was independent of these parameters but positively associated with lobular type. This correlation was also observed for BM status, which was similarly independent of the tumour characteristics.No association was found between SN status and BM status.Our data indicate that, in the course of breast cancer, OTC spreading is frequent and could be an early event, related to lobular histological type but independent of classical histoprognostic parameters, and that the loco-regional metastatic spread of OTC is not a prerequisite for systemic involvement.     

A case of confusional migraine with transient increased cerebral blood flow

Background

Confusional migraine is a rare type of migraine presenting as an acute confusional state. However, the mechanism of this confusional state remains unclear.

Epithelial Cell Nodules Developing in the Cecum of Irradiated Mice

A method for producing macroscopic epithelial nodules was developed in order to investigate the properties of epithelial stem cells in the large intestine of mice. The cecum was exteriorized and exposed to various doses of X-ray radiation. Numbers of nodules subsequently developing were counted and plotted against radiation dose. From the logarithmic regression line, the susceptibility to irradiation of nodule forming stem cells (NFSC) was determined. The susceptibility of cecal NFSC was comparable to the value reported for jejunal NFSC. Mice of (C57BL/6XDS) F₁-Pgk-1^b/Pgk-1^a that carried X chromosome inactivation mosaicism for the phosphoglycerate kinase gene were used for examination of nodule clonality. Most cecal nodules contained only 1 type of phosphoglycerate kinase, suggesting a monoclonal origin of the nodules. Histochemical studies showed the presence of absorptive epithelial, goblet and entero endocrine cells in 17 day old nodules, implying multipotentiality of the NFSC. In spite of these similarities between cecal and jejunal NFSC, the macroscopic appearance of cecal nodules was quite different from that of jejunal nodules. Only crypt like structures were observed in the former, whereas both crypt like and villus like structures were present in the latter. A comparison between cecal and jejunal nodules may be useful for understanding the morphogenesis of the intestinal mucosa. Acta Pathol Jpn 40: 880–886, 1990.     

Calcification of the portal vein associated with hepatocarcinoma]

We report a patient with alcoholic cirrhosis presenting with ascites, jaundice and malaise. Linear calcifications on the portal area were seen in the plain film of the abdomen. Computed tomography confirmed the presence of calcification of the portal vein wall and discovered lesions highly suggestive of diffuse multinodular hepatocarcinoma. We emphasize the rarity of portal vein calcification in patients with portal hypertension secondary to hepatic cirrhosis and hepatocarcinoma.