Expression and localization of osteopontin, homing cell adhesion molecule/CD44, and integrin αvß3 in mucoepidermoid carcinoma and acinic cell adenocarcinoma of salivary gland origin.

OBJECTIVE: Osteopontin (OPN) plays a role in tumor progression. This study aimed to determine the expression of OPN, CD44, and integrin αvß3 in pleomorphic adenoma (PA), acinic cell adenocarcinoma (ACA), and mucoepidermoid carcinoma (MEC). STUDY DESIGN: Immunohistochemistry was used to semiquantify the levels of expression of OPN and its receptors in normal salivary glands (NSG) (n = 20), PA (n = 20), ACA (n = 11), and MEC (n = 29). RESULTS: OPN expression was increased in ACA and MEC compared with PA and NSG (median scores, 6, 6, 4, and 4, respectively). CD44 expression was increased in ACA and reduced in MEC and PA compared with NSG (median scores, 8, 4, 3, and 5, respectively). Integrin αvß3 median scores were 5 in ACA, 1 in MEC, and 0 in PA and NSG. CONCLUSIONS: OPN is expressed in salivary gland tumors and is at higher levels in ACA and MEC.

Expression and localization of osteopontin, homing cell adhesion molecule/CD44, and integrin αvß3 in pleomorphic adenoma, polymorphous low-grade adenocarcinoma, and adenoid cystic carcinoma.

OBJECTIVES: Osteopontin (OPN) plays a role in tumor progression. This study aimed to determine the expression of OPN, CD44, and integrin αvß3 in pleomorphic adenoma (PA), polymorphous low-grade adenocarcinoma (PLGA), and adenoid cystic carcinoma (ACC). STUDY DESIGN: Immunohistochemistry was used to semiquantify the level of expression of OPN and its receptors in normal salivary glands (NSG; n = 20), PA (n = 20), PLGA (n = 16), and ACC (n = 22). RESULTS: OPN expression was increased in PLGA and intermediate-/high-grade ACC compared with PA and NSG (median scores, 6, 5, 4, and 4, respectively). CD44 expression was reduced in PA, PLGA, and ACC. OPN expression levels were moderately correlated with CD44 in PLGA. Integrin αvß3 was not expressed in PA and ACC and was seen in only 1 case of PLGA. CONCLUSIONS: OPN is expressed in salivary gland tumors but does not correlate well with CD44 and αvß3.

Nifedipine induces periostin expression in gingival fibroblasts through TGF-beta.

Gingival enlargement is a fibrotic condition that can arise from systemic administration of the dihydropyridine calcium channel blocker nifedipine. Periostin, a transforming growth factor-beta (TGF-ß)-inducible matricellular protein, has been associated with fibrosis in numerous tissues, but its expression has never been examined in nifedipine-influenced gingival enlargement (NIGE). The objective of this study was to assess if periostin up-regulation is associated with NIGE and whether nifedipine induces periostin expression in gingival fibroblasts. In NIGE tissue (n = 6), periostin is overexpressed in the gingival connective tissue compared with healthy control tissue (n = 6). The transcription factor p-SMAD2/3, which is associated with canonical TGF-ß signaling, localizes to the nuclei in both HGFs and oral epithelial cells in NIGE tissues, but not in control healthy tissue. In vitro culture of HGFs with 30 and 100 ng/mL of nifedipine significantly increased periostin mRNA and protein levels, which correlated with increased levels of active TGF-ß and increased phosphorylation and nuclear localization of SMAD3. Blocking of canonical TGF-ß signaling through inhibition of the TGF-ß receptor I with SB431542 significantly reduced nifedipine-induced SMAD3 phosphorylation and periostin expression. Our results demonstrate that nifedipine up-regulates periostin in HGFs in a TGF-ß-dependent manner.

The expression and immunohistochemical localization of periostin in odontogenic tumors of mixed epithelial/mesenchymal origin.

OBJECTIVE: The object of this study was to determine the expression and localization of periostin in the major mixed odontogenic tumors and to correlate any differential staining of the mesenchymal components to the interrelationship of these tumors. STUDY DESIGN: Five ameloblastic fibromas, 8 ameloblastic fibro-odontomas and 10 odontomas were assessed immunohistochemically for periostin staining. Because mesenchymal tissues were consistently present in all studied cases, these tissues were selected for statistical analysis of differential periostin staining. RESULTS: Periostin was variably localized to the mesenchymal component of the tumors as well as to preameloblasts and ameloblasts. Analysis of the mesenchymal staining intensity was statistically significantly different between ameloblastic fibro-odontomas and odontomas (P < .001; Dunn multiple comparisons test). CONCLUSIONS: Our results document periostin staining in human mixed odontogenic tumors. Statistical analysis of differential stromal staining supports the concept that the ameloblastic fibroma is a histogenetically distinct neoplasm as compared to ameloblastic fibro-odontoma and odontoma.

Unusual benign smooth muscle lesions of the tongue: review and report of two cases.

Benign smooth muscle proliferations are relatively rare in the oral cavity. Most are classified as angioleiomyomas, some as hamartomatous growths and a few as cutaneous-type leiomyomas. We present two cases of benign smooth muscle proliferations in the tongue, provide a review, briefly discuss histogenesis and offer a clinico-pathological differential diagnosis.

Human kallikrein 3 (prostate specific antigen) and human kallikrein 5 expression in salivary gland tumors.

The human kallikrein 5 protein (hK5) is expressed in many normal tissues, most notably in skin, breast, salivary gland and esophagus. It has also been shown to be a potential biomarker for breast, ovarian and testicular cancer. Human kallikrein 3 (hK3; prostate-specific antigen) is the most useful marker for adenocarcinoma of the prostate gland. The aim of this study was to determine whether hK3 and hK5 are expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), in order to compare normal with tumor tissues. Pleomorphic adenomas, adenoid cystic carcinomas, polymorphous low-grade adenocarcinomas, acinic cell carcinomas, mucoepidermoid carcinomas and adenocarcinomas not otherwise specified of both minor and major salivary glands were examined. The results of this study indicate that most salivary gland tumors do not show high levels of expression of hK5. Staining was most prominent in keratinizing epithelia in pleomorphic adenomas. hK3 is not expressed in salivary gland tumors.

Human kallikrein 13 expression in salivary gland tumors.

The human kallikrein 13 protein (hK13) is expressed in many normal tissues. Petraki et al have previously described presence of hK13 in salivary gland tissue, localized to duct epithelia and some acinar cells. The aim of this study was to determine whether hK13 is expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), in order to compare normal with tumor tissues. Pleomorphic adenomas (PA), adenoid cystic carcinomas (ACC), polymorphous low grade adenocarcinomas (PLGA), acinic cell carcinomas (ACI), mucoepidermoid carcinomas (MEC) and adenocarcinomas not otherwise specified (ANOS) of both minor and major salivary glands were examined. The results of this study indicate that most salivary gland tumors show high levels of expression of hK13. Overall, staining in PA was significantly less than that seen in normal salivary gland tissue. PLGA, ACC and ANOS each stained significantly more than normal salivary gland tissue while MEC and ACI did not. Ductal cells and cells lining duct-like structures showed a higher intensity of staining than non-ductal cells in most tumors. Tumors which exhibited only non-ductal cells also exhibited cytoplasmic staining. In conclusion, we demonstrate the high expression of hK13 in several common salivary gland tumors.

Peripheral ameloblastic fibroma.

Peripheral ameloblastic fibroma is an exceedingly rare lesion. Only three reports could be found, two of which appeared in the Japanese literature. Here, we report a case of peripheral ameloblastic fibroma occurring in a 5-year-old girl. The diagnosis was made after careful microscopic examination, to exclude other lesions. The lesion was excised and has not recurred 1 year after removal.

Osteopontin expression in salivary gland tumours.

Osteopontin (OPN) is expressed in numerous carcinomas and plays a role in tumour development, invasion and metastasis. This study examines by immunohistochemistry the expression of OPN in normal salivary gland tissue and three types of salivary gland tumour: pleomorphic adenoma (PA), adenoid cystic carcinoma (ACC) and polymorphous low grade adenocarcinoma (PLGA). PAs and PLGAs demonstrated higher levels of OPN than normal salivary gland tissue, while ACC, although showing a trend towards increased OPN, was not significantly different. The results of this study indicate that OPN expression is present in normal salivary gland tissue, and is increased in certain salivary gland tumours, but further investigation is necessary to clarify its role.

Human kallikrein 6 expression in salivary gland tumors.

Human kallikrein 6 (hK6), also known as zyme/protease M/neurosin), is expressed in many normal glandular tissues. The aim of this study was to determine whether hK6 is expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), using an immunohistochemical method. Pleomorphic adenomas (PA), adenoid cystic carcinomas, polymorphous low-grade adenocarcinomas, acinic cell carcinomas, mucoepidermoid carcinomas, and adenocarcinomas not otherwise specified of both minor and major salivary glands were examined. Cells lining duct-like structures and non-duct-like cells were scored. Only in PA of minor salivary gland origin was overall staining higher in duct-like than in non-duct-like cells. In all other tumors exhibiting both types of cells, hK6 staining was similar in both duct-like and non-duct-like cells. Tumors that exhibited non-duct-like cells only also exhibited cytoplasmic staining. Results of this study show that salivary gland tumors express hK6, apparently downregulated in comparison with normal salivary gland tissue, and that this expression is not specific for any of the tumors studied.

The relation between maternal work, ambulatory blood pressure, and pregnancy hypertension.

STUDY OBJECTIVE: The purpose of the study was to determine the relations between maternal work, ambulatory blood pressure in mid-pregnancy, and subsequent pregnancy outcome. DESIGN: Data were studied on 933 healthy normotensive primigravidas who had been enrolled into a study on the predictive value of ambulatory blood pressure measurement performed between 18 and 24 weeks gestation. They were classified into three groups depending on whether they were at work (working group, n=245), not working (not working group, n=289), or normally employed but chose not to work (ENK group, n=399), on the day monitoring was performed. SETTING: The Rotunda Hospital (a large maternity hospital), Dublin, Ireland. MAIN RESULTS: Adjusted for age, body mass index, smoking, drinking, and marital status, women at work had higher mean daytime systolic (p<0.01) and diastolic (p<0.01) and 24 hour systolic pressures (p=0.03) compared with those not working. The rate of subsequent development of pre-eclampsia was significantly higher (odds ratio 4.1, 95% CI 1.1 to 15.2, p=0.03) among those at work compared with those not working. The association between pre-eclampsia and maternal work remained significant (odds ratio 5.5, 95% CI 1.1 to 27.8, p=0.04) even after allowing for the confounding factors of age, smoking, body mass index, and marital status. When daytime systolic and diastolic blood pressure were added to the regression analysis the risk ratios for pre-eclampsia remained high but did not quite reach statistical significance (odds ratio 4.7, 0.90 to 24.8, p=0.066). Birth weight and placental weight were not predicted by work status or blood pressure. CONCLUSIONS: A significant independent relation was found between maternal work and ambulatory blood pressure levels in mid-pregnancy. In addition, it was found that maternal work was significantly associated with the subsequent development of pre-eclampsia

Human vaginal epithelium and the epithelial lining of a cyst model constructed from it: a comparative light microscopic and electron microscopic study.

The light microscopic features and keratin filament distribution of human vaginal epithelium resemble those of buccal mucosa. We used vaginal epithelium to establish a human cyst model in immunodeficient mice. To strengthen the view that this experimental cyst is a suitable model to study mucosal diseases, we compared specific light microscopic and ultra-structural features of vaginal epithelium and the epithelial lining of the cyst. Nineteen cyst walls and 6 specimens of vaginal mucosa, which had been used to establish the cysts, were examined. We counted the number of cell layers of 17 cyst linings and the 6 vaginal specimens. Surface keratinisation was evaluated on sections stained with the Picro-Mallory method. To demonstrate intercellular lamellae and membrane coating granules 2 cyst linings were examined ultra-structurally. The epithelium lining of the cyst wall was thinner than that of vaginal mucosa but the surface keratinisation and ultra-structural features of the intercellular lamellae and membrane coating granules were similar. We concluded that vaginal mucosa is a useful substitute for oral mucosa in the cyst model.

The relationship between increased folate catabolism and the increased requirement for folate in pregnancy.

OBJECTIVES: To estimate the rate of folate catabolism in pregnant and nonpregnant women and to derive the recommended dietary allowance for folate. DESIGN: Prospective, observational study. SETTING: Rotunda Hospital, Dublin. WOMEN: Twenty-four healthy gravid women were studied once during each trimester and postpartum. Twenty-five nonpregnant controls were assessed before and after folic acid supplementation. INTERVENTIONS: Women provided 24-hour urine collections while adhering to a strict dietary regimen containing no exogenous folate catabolites. MAIN OUTCOME MEASURES: Urinary levels of p-acetamidobenzoylglutamate and p-aminobenzoylglutamate were measured by high pressure liquid chromatography. RESULTS: The 24-hour excretion of folate catabolites, expressed as mean [95% CI] folate equivalents in microg) progressively increased during pregnancy. A peak was reached in the third trimester (349.1 microg [308.1 to 390.1]) where the rate was more than twice the rate in the nonpregnant control group (136.4 microg [112.4 to 160.4]) (P < 0.001). Based on our results the recommended dietary allowance for folate in nonpregnant women should be 250 microg and this should rise during pregnancy to 430 microg in the second trimester and 540 microg in the third trimester. CONCLUSIONS: The rate of folate catabolism progressively increases during pregnancy reaching a peak in the third trimester at the time of maximal fetal growth. The increased demand for folate during pregnancy appears to be due to the accelerated breakdown of the vitamin because of its participation in cellular biosynthesis. These results provide a quantitative basis for the current debate on the appropriate recommended dietary allowance for folate in both pregnant and nonpregnant women.

Nitric oxide in the uteroplacental, fetoplacental, and peripheral circulations in preeclampsia.

OBJECTIVE: Altered production of nitric oxide by the vascular endothelium may influence the pathogenesis of preeclampsia. The aim of this study was to measure circulating levels of nitric oxide metabolites (nitrites) in the uteroplacental, fetoplacental, and peripheral circulation of preeclamptic pregnancies compared with normotensive controls. METHODS: Fifteen women with preeclampsia were compared with 16 women with normotensive pregnancies. At cesarean, blood samples were taken from the uterine vein draining the placental site, the umbilical vein, and the antecubital vein after delivery of the baby but before delivery of the placenta. Plasma nitrites were measured using the Greiss reaction after conversion of plasma nitrates to nitrites using nitrate reductase. RESULTS: Nitric oxide metabolites were higher in the uteroplacental (P < .01), fetoplacental (P < .001), and peripheral (P < .02) circulations in samples from preeclamptic pregnancies compared with control pregnancies. In samples from the fetoplacental circulation only, nitric oxide metabolite levels were negatively correlated with gestational age (r = -.489, P < .01) and birth weight (r = -.544, P < .004). Nitric oxide metabolite levels were not significantly correlated with blood pressure, placental weight, or maternal age. CONCLUSION: In established preeclampsia, production of nitric oxide was higher in the uteroplacental, fetoplacental, and peripheral circulation than in normotensive pregnancies. This increase may be part of a compensatory mechanism to offset the pathologic effects of preeclampsia.

Circulating vascular cell adhesion molecule-1 in pre-eclampsia, gestational hypertension, and normal pregnancy: evidence of selective dysregulation of vascular cell adhesion molecule-1 homeostasis in pre-eclampsia.

OBJECTIVE: Our purpose was to investigate circulating levels of vascular cell adhesion molecule-1 in the peripheral and uteroplacental circulations during normotensive and hypertensive pregnancies. STUDY DESIGN: This prospective observational study involved 2 patient groups. Group 1 consisted of 22 women with pre-eclampsia and 30 normotensive women followed up longitudinally through pregnancy and post partum. There were an additional 13 women with established gestational hypertension. Group 2 consisted of 20 women with established pre-eclampsia and 19 normotensive control subjects undergoing cesarean delivery. Plasma levels of vascular cell adhesion molecule-1 were measured in blood drawn from the antecubital vein (group 1) and from both the antecubital and uterine veins (group 2). Data were analyzed by analysis of variance. RESULTS: In group 1 vascular cell adhesion molecule-1 levels did not change significantly throughout normal pregnancy and post partum. Women with established pre-eclampsia had increased vascular cell adhesion molecule-1 levels compared with the normotensive pregnancy group (P = .01). Vascular cell adhesion molecule-1 levels were not elevated in women with established gestational hypertension. In group 2 significantly higher levels of vascular cell adhesion molecule-1 were detected in the uteroplacental (P < .0001) and peripheral (P < .0001) circulations of pre-eclamptic women by comparison with normotensive women. In the pre-eclamptic group there was a tendency toward higher vascular cell adhesion molecule-1 levels in the peripheral circulation than in the uteroplacental circulation (P = .06). In contrast to vascular cell adhesion molecule-1, circulating levels of E-selectin and intercellular adhesion molecule-1, other major leukocyte adhesion molecules expressed by the endothelium, were not different in pre-eclamptic and normotensive pregnancies. CONCLUSION: Established pre-eclampsia is characterized by selective dysregulation of vascular cell adhesion molecule-1 homeostasis. This event is not an early preclinical feature of pre-eclampsia, does not persist post partum, is not a feature of nonproteinuric gestational hypertension, and is not observed with other major leukocyte adhesion molecules. Induction of vascular cell adhesion molecule-1 expression in pre-eclampsia may contribute to leukocyte-mediated tissue injury in this condition or may reflect perturbation of other, previously unrecognized, functions of this molecule in pregnancy.

Hemostasis in the uteroplacental and peripheral circulations in normotensive and pre-eclamptic pregnancies.

OBJECTIVE: Our purpose was to determine the hemostatic changes in the uteroplacental and peripheral circulations in normotensive and pre-eclamptic pregnancies. STUDY DESIGN: This prospective, observational study involved 2 patient groups. Group 1 consisted of 30 normotensive women and 22 women with pre-eclampsia who were followed up longitudinally through pregnancy and post partum. Group 2 consisted of 20 women with established pre-eclampsia and 19 normotensive control subjects, all undergoing cesarean section. Plasma levels of thrombin-antithrombin III complex, soluble fibrin, plasmin-alpha2-antiplasmin complex, and fibrin-degradation product (D-dimer) were measured in blood drawn from the antecubital vein (group 1) and from both the antecubital and uterine veins (group 2). Data were analyzed by analysis of variance. RESULTS: In group 1 levels of thrombin-antithrombin III complex, soluble fibrin, and fibrin-degradation product were significantly higher during normal pregnancy than at 6 weeks post partum. Plasmin-alpha2-antiplasmin complex levels did not change. No differences between the pre-eclamptic and normotensive pregnancy groups were found for any of the hemostatic markers. In group 2 normotensive women undergoing cesarean section, thrombin-antithrombin III complex and soluble fibrin levels were significantly higher in the uterine vein than in the antecubital vein. In group 2 women with pre-eclampsia, thrombin-antithrombin III complex and fibrin-degradation product levels were significantly higher in the uterine vein than in the antecubital vein. In addition, plasmin-alpha2-antiplasmin complex and fibrin-degradation product levels were higher and soluble fibrin levels were lower in the uterine vein in the pre-eclamptic group than in the normotensive group. CONCLUSION: Both the coagulation and fibrinolytic systems are activated during normal pregnancy. Activation of these systems is more marked in the uteroplacental circulation than in the systemic circulation in both normotensive and pre-eclamptic pregnancies. An abnormal pattern of hemostasis occurs in the uteroplacental circulation in pre-eclampsia.

Can 24-hour ambulatory blood pressure measurement predict the development of hypertension in primigravidae?

OBJECTIVE: To assess the role of 24-hour ambulatory blood pressure measurement in the mid-second trimester as a predictive test for the development of hypertension in pregnancy. DESIGN: Prospective intervention. SETTING: The Rotunda Hospital, Dublin. PARTICIPANTS: One thousand one hundred and two healthy primigravid women. INTERVENTION: 24-hour ambulatory blood pressure measurement at 18 to 24 weeks of gestation. MAIN OUTCOME MEASURES: The development of pre-eclampsia or gestational hypertension. RESULTS: A total of 1048 women had sufficient readings to be included in the final analysis. Of these, 23 (2.2%) developed pre-eclampsia, 64 (6.1%) developed gestational hypertension and 961 (91.7%) remained normotensive. Significantly higher ambulatory blood pressures were recorded in both the pre-eclamptic and gestational hypertensive group compared with the normotensive group. In addition, the gestational hypertensive group had significantly higher clinically measured blood pressure compared with the normotensive group. There were no differences between the pre-eclamptic and the gestational hypertensive group for any of the blood pressure parameters analysed. The best overall predictor for pre-eclampsia was 24-hour mean diastolic pressure which using a cutoff level of 71 mmHg gave a test with a sensitivity of only 22% and a positive predictive value of 15%. CONCLUSION: Because the absolute differences are small and the overlap between the hypertensive and normotensive groups large, ambulatory blood pressure measurement, in a healthy primigravid population, between 18 and 24 weeks of gestation is not a useful predictor of hypertension.