In situ localization of cell synthesis and proliferation in periodontitis gingiva and tonsillar tissue

OBJECTIVE: Previous work indicates that large numbers of B and T cells accumulate in the periodontal soft tissues although we know little about cellular synthetic activity and proliferation at this site. The aim of this study was to examine lymphocytic cell synthetic activity and proliferation in periodontitis gingiva and compare this to a known site of leucocyte proliferation, namely the oro-pharyngeal tonsils. MATERIALS AND METHODS: Messenger RNA (mRNA) and 285 ribosomal RNA (285 rRNA) expressing cells in formalin-fixed/paraffin-embedded gingival and tonsillar tissue sections were detected by in situ hybridisation (ISH) using poly-deoxyribothymidine and 28S probes respectively. In addition S-phase proliferating and cycling cells were also detected by ISH with histone probes and by Ki-67 immunohistochemistry. Ten gingival biopsy samples were obtained from adult periodontitis patients and five tonsillar biopsies from tonsillectomy patients. RESULTS: Both mRNA and 28S rRNA-expressing cells were detected in all the samples tested. Plasma cells showed the strongest signal for the two probes and slight to moderate staining could be seen in epithelium, fibroblasts and endothelial cells. In contrast, gingival lymphocytes were either weakly stained or were unstained for these probes of synthetic activity. In tonsils, most lymphocytes in germinal centres showed moderate staining and mantol zone cells were much more weakly stained. In gingival samples, histone mRNA-expressing and cycling (Ki-67) cells were detected in 4/10, 10/10 cases respectively. These positive cells were mainly basal and suprabasal epithelial cells and a few mononuclear cells, whereas most germinal centre lymphocytes (B cells) were positive for this probe. The number of Ki67 positive cells was greater than histone mRNA bearing cells both in gingiva and tonsillar tissue. In contrast, mantol zone cells (mainly T cells) were sparsely stained by probes of cell proliferation. CONCLUSION: These results indicate that local proliferation of B cells does not occur in periodontitis gingiva in contrast with tonsillar tissue, although plasma cells showed strong synthetic activity in both tissues. T cells did not appear to proliferate greatly nor undergo active synthesis in either of these tissues. These findings substantiate previous hypotheses that specific leucocytes predominate in the gingival tissue through selective homing rather than by local proliferation.     

MGA3 A New Paradigm for Assessing Health-Related Quality of Life: A Social-Clinical Model

The objectives of this study were to confirm the factorial validity of a health-related quality of life (HRQL) instrument (Functional Assessment of Cancer Therapy), establish equivalence of the HRQL instrument across three racial/ethnic groups, and examine the impact of social and clinical factors on HRQL in diverse cancer patients.
METHODS: Data used in this study were supplied by three Eastern Cooperative Oncology Group (ECOG) data collection sites. A total of 911 patients with complete data were included in the cross-sectional analyses. This study includes seven exogenous (observed) variables (age, socio-economic status, living arrangement, gender, race/ethnicity, disease stage, and performance status) and one exogenous latent variable (spiritual beliefs). The multivariate analyses include exploratory factor analysis, confirmatory factor analysis, and structural equation modeling.
RESULTS: The construct validity of a commonly used HRQL instrument has been demonstrated in this study sample. The results indicate that HRQL is a multidimensional construct, which is composed of the dimensions of physical well-being, social well-being, emotional well-being, and functional well-being. The HRQL measurement model is universally applicable, irrespective of race and/or ethnicity, and the factor loadings are the same across the three groups. The findings indicate that one's "spiritual beliefs," a social factor, is the most significant determinant of HRQL followed by a clinical attribute, performance status.
CONCLUSION: HRQL assessment plays a crucial role in health services research and clinical practice. It is hoped that this research has furthered the discussion on the social and clinical determinants of HRQL. The application of a HRQL instrument using confirmatory factor analysis in multiple racial/ethnic groups in this study has demonstrated a new methodological approach to validation research.     

Malignant vulvar melanoma: colposcopic evaluation and review of the literature. A case report

Because of the rarity of this kind of vulvar neoplasia, the diagnostic difficulties (clinical and histopathological) conditioning the therapeutic approach and the missing iconographical material, we report a case of vulvar melanoma seen at the Department of Obstetrics and Gynecology of the University of L'Aquila in April 2001, together with a review of the literature. Owing to radical vulvectomy and bilateral inguinal lymphadenectomy with the Byron three-incision approach the histological report was: epithelioid cell apigmented melanoma radially spreading (MMSS), a tumor-free margin of at least 1.7 cm with sufficient lympholitic infiltration.     

Role of HSP90, CDC37, and CRM1 as modulators of P16(INK4A) activity in rat liver carcinogenesis and human liver cancer

Current evidence indicates that neoplastic nodules induced in liver of Brown Norway (BN) rats genetically resistant to hepatocarcinogenesis are not prone to evolve into hepatocellular carcinoma. We show that BN rats subjected to diethylnitrosamine/2-acetylaminofluorene/partial hepatectomy treatment with a "resistant hepatocyte" protocol displayed higher number of glutathione-S-transferase 7-7(+) hepatocytes when compared with susceptible Fisher 344 (F344) rats, both during and at the end of 2-acetylaminofluorene treatment. However, DNA synthesis declined in BN but not F344 rats after completion of reparative growth. Upregulation of p16(INK4A), Hsp90, and Cdc37 genes; an increase in Cdc37-Cdk4 complexes; and a decrease in p16(INK4A)-Cdk4 complexes occurred in preneoplastic liver, nodules, and hepatocellular carcinoma of F344 rats. These parameters did not change significantly in BN rats. E2f4 was equally expressed in the lesions of both strains, but Crm1 expression and levels of E2f4-Crm1 complex were higher in F344 rats. Marked upregulation of P16(INK4A) was associated with moderate overexpression of HSP90, CDC37, E2F4, and CRM1 in human hepatocellular carcinomas with a better prognosis. In contrast, strong induction of HSP90, CDC37, and E2F4 was paralleled by P16(INK4A) downregulation and high levels of HSP90-CDK4 and CDC37-CDK4 complexes in hepatocellular carcinomas with poorer prognosis. CDC37 downregulation by small interfering RNA inhibited in vitro growth of HepG2 cells. In conclusion, our findings underline the role of Hsp90/Cdc37 and E2f4/Crm1 systems in the acquisition of a susceptible or resistant carcinogenic phenotype. The results also suggest that protection by CDC37 and CRM1 against growth restraint by P16(INK4A) influences the prognosis of human hepatocellular carcinoma.     

Long-term dehydroepiandrosterone and 16alpha-fluoro-5-androsten-17-one administration enhances DNA synthesis and induces expression of c-fos and c-Ha-ras in a selected population of preneoplastic lesions in liver of diethylnitrosamine-initiated rats

Dehydroepiandrosterone (DHEA) inhibits glucose 6-phosphate dehydrogenase (G6PD) activity and growth of preneoplastic lesions in various tissues, but its administration may also enhance tumorigenesis by genotoxic carcinogens. We have investigated in single preneoplastic liver lesions, induced in diethylnitrosamine-initiated rats by the resistant hepatocyte protocol, the mechanisms underlying these opposite DHEA effects. Administration of DHEA (0.45% in the diet) for 10 and 26 weeks and of its analog 16alpha-fluoro-5-androsten-17-one (FA, 0.25%) for 10 weeks, starting 4 weeks after initiation, induced an apparent decrease in the number of glutathione S:-transferase (placental) (GST-P)-positive lesions and an increase in lesion volume. DHEA administration for 38 weeks enhanced hepatocellular carcinoma multiplicity. Depending on the rise in the number of slowly growing, remodeling GST-P-positive lesions induced by DHEA and FA, overall DNA synthesis decreased slightly in these lesions at 14 weeks, but increased in uniform lesions. Labeling index (LI) in single uniform lesions at 14 weeks ranged between very low (not different from normal liver) to high (>10-fold normal liver). DHEA and FA induced broad increases in lesions with a high LI, which showed a higher number of cells overexpressing c-Ha-ras and/or c-fos than those with a lower LI. High G6PD activity was inhibited by DHEA and FA in only approximately 50% of preneoplastic lesions. These data indicate selection in rats subjected to long-term DHEA and FA treatments of a subpopulation of GST-P-positive cells with high growth and progression potentials. Overall effects of these compounds depends on the relative numbers of lesions in which inhibition of DNA synthesis can counteract their transforming effect.     

Superior vena caval placement of a Kimray-Greenfield filter

Kimray-Greenfield filters placed in the inferior vena cava have been shown effective for prophylaxis against pulmonary embolism from lower extremity or pelvic thrombi. Percutaneous filter placement in the superior vena cava is described in a patient with pulmonary embolism and upper extremity thrombosis in whom anticoagulative therapy was contraindicated.