Sensitivity of young rats to nicotine exposure: Physiological and biochemical parameters.

This work has investigated the effects of prolonged exposure of young rats to nicotine on some physiological and biochemical parameters. Wistar male rats (30 days old) were treated (s.c.) with saline or nicotine 5mg/kg/day for 28 or 56 days. They received five injections (1mg/kg) per day (8, 10, 12:00 a.m., 2 and 4:00 p.m.) on the dark period of the cycle. Nicotine exposure for 56 days reduced body and liver weights. Moreover, nicotine exposure for 28 or 56 days decreased the hepatic glycogen but not blood glucose levels. The activities of blood and hepatic PBG-synthase, and blood and cerebral acetylcholinesterase were not affected by in vivo exposure. However, these activities were inhibited by nicotine in vitro. Results show that although high levels of plasma cotinine were found in both intervals of exposures, the parameters here analyzed were not affected by prolonged nicotine exposure except the storage of glucose, and body and liver weights.

Primary carcinoid tumor of the cystic and common bile ducts.

We report a case of primary carcinoid tumor arising at the confluence of the cystic and common bile ducts. The patient was a 64-year-old woman who developed a sudden onset of biliary colic and jaundice. Computerized tomography and nuclear magnetic resonance showed a mass lesion close to the head of the pancreas. At laparotomy a nodular lesion was found at the confluence of the cystic and common bile ducts. Microscopic observation revealed a type B-C carcinoid (Soga's classification) with positive immunoreactivity to chromogranin and cytokeratin. The presence of neurosecretory intracytoplasmic granules was demonstrated by electron microscopy. Flow cytometry showed diploid DNA content of the neoplastic cells with less than 5% of the nuclei in the S-phase region.

A coordinated proto-oncogene expression characterizes MCF 247 murine leukemia virus-induced T-cell lymphomas irrespectively of proviral insertion affecting myc loci.

Proto-oncogene transcriptional activation was analyzed in a group of MCF 247 MuLv-induced T-cell lymphomas to identify transformation-specific gene activations and determine whether the proviral insertion near a myc gene could promote a peculiar mechanism of transformation through a differential proto-oncogene expression pattern. Of the six lymphomas analyzed, three showed the MCF 247 provirus integrated within the N-myc locus, one carried the provirus integrated near c-myc, whereas for the remaining two, no evidence of proviral integrations in any of the known myc loci was obtained. Independently of the integrative events, the pattern of proto-oncogene expression was almost identical in all six lymphomas. These findings seem to rule out the existence of a peculiar pathway of transformation associated with the proviral insertion near a myc locus. Moreover, the transcription pattern observed was qualitatively identical to that displayed by normal thymocytes; only quantitative differences in c- or N-myc, c-myb and Ha-ras were observed. These results suggest that the T-cell proto-oncogene activation program is not qualitatively affected by the transforming event(s).

Efficiency of different polyacrylic acid concentrations on the smear layer, after ART technique, by Scanning Electron Microscopy (SEM).

AIM: To assess the efficiency of different polyacrylic acid concentrations on the removal of the smear layer after caries removal with hand and rotary instruments in affected dentine of primary teeth. STUDY DESIGN: In vitro study. METHODS: Six exfoliated primary molars with carious lesions were divided into two groups for caries removal: (1) hand instrument or (2) low speed bur. Each tooth was cut into four pieces. One piece assigned as control surface and the other three surfaces were actively treated with either 40% Fuji IXGP Liquid (GC America), or 40% Fuji IXGP Liquid diluted with water, and 25% Ketac Molar(TM) Conditioner (3M-ESPE). Surfaces were prepared for scanning electron microscopy (SEM). All images were submitted to an analysis by an experienced SEM professional, regarding presence or absence of smear layer and dentinal demineralization pattern. Chi-squared test was carried out (5% significance). RESULTS: There was no difference concerning the presence of a smear layer in relation to the method of caries removal, and 40% Fuji IXGP diluted with water causes a higher demineralization when compared with the control group of teeth (p=0.01). CONCLUSION: Treatments with polyacrylic acid are indicated prior to glass ionomer cement application in primary teeth.

Social "status" and biological "status": a comparison of grave goods and skeletal indicators from Pontecagnano.

Comparison of funerary treatment and skeletal biology can be very informative about the interplay of social status and meanings and actual life conditions in ancient communities, but such comparison is rarely done, due in part to the disciplinary separation of bioanthropology and social archaeology in many archaeological traditions. In this paper, we analyze relations between skeletal pathologies and grave goods in a sample of 94 individuals from Pontecagnano (Salerno, Italy, seventh-third centuries BC). The results show that the relationship between health, activity, and social status as expressed in grave goods was complex. Some biological indicators considered typical of "stress" or biological status (enamel hypoplasia, cribra orbitalia, adult stature) bore no relation to social status. Other indicators, particularly those of activity and stress in adult life (trauma, Schmorl's nodes, periostitis), covaried with grave assemblage and help to outline a possible division of labor. As this analysis shows, when skeletal and archaeological data are used in conjunction, the result is a deeper picture of the social and economic life of the community than can be obtained from either source.

Establishment and characterization of a leukemic murine cell line derived from MCF 247 MuLV-induced T-cell lymphoma.

Understanding of the leukemic evolution of human non-Hodgkin's lymphomas is hindered by the lack of appropriate animal models. For this purpose, a highly leukemic cell line NQ22, derived from a MCF 247 murine leukemia virus (MuLV)-induced murine T-cell lymphoma, was established, and its preliminary characterization is described. The NQ22 cell line is easily transplantable subcutaneously (s.c.) into syngeneic AKR mice exhibiting early peripheral blood invasion and widespread dissemination with a leukemic pattern of infiltration. Such peculiar in vivo behavior is a stable phenotypic feature, probably determined genetically. Biological and differentiation characteristics of the NQ22 cell line were analyzed and compared to those of other non-leukemic T-lymphoma lines. In addition, no evidence of possible involvement of plasminogen activator (PA) enzymes and of their inhibitors (PAI) in the spreading ability of NQ22 cells was observed.

Gastric epithelial dysplasia. How clinicopathologic background relates to management.

BACKGROUND: Gastric epithelial dysplasia (GED) in metaplastic mucosa is considered the most advanced preinvasive lesion in the multistep morphogenesis of intestinal-type gastric cancer (GC). The rate of GED's evolution into GC is still under debate and probably is related to pathologic and clinical parameters other than the dysplasia itself. The aim of this study was to evaluate whether clinical aspects (sex and age) and/or morphologic variables (GED grade, coexisting atrophic gastritis) are relevant to the outcome of dysplasia, with a view toward initiating the establishment of a rational follow-up protocol for practical GED management. METHODS: Ninety-three patients harboring GED (G1: 56, G2:34, G3:18) were followed for more than 12 months according to a previously-agreed protocol. Regression, progression, or evolution into GC were detected for each grade of GED. Multivariate analysis was used to check the independence of clinical and pathologic variables in the progression of GED into more severe dysplastic lesions and/or as risk factors for evolution into GC. RESULTS: Age, male sex, GED grade and grade of coexisting atrophic gastritis proved independent risk factors for GED progression, with no significant interactions. Only GED grade (G2 and G3) was significantly associated with carcinomatous evolution. In G1-GED, age and the grade of coexisting atrophy proved to be independent risk factors for carcinomatous evolution. CONCLUSIONS: In G1-GED, more stringent follow-up should be recommended for older patients with coexisting high grade atrophic gastritis; stringent follow-up is always mandatory for G2-GED; and a surgical approach is justified in G3-GED.

Gastric epithelial dysplasia in the natural history of gastric cancer: a multicenter prospective follow-up study. Interdisciplinary Group on Gastric Epithelial Dysplasia.

BACKGROUND/AIMS: Because the precancerous significance of gastric epithelial dysplasia (GED) is still under debate, this study attempts to ascertain whether a prospective follow-up of GED can contribute to clarifying its clinical and pathological relationships with gastric cancer (GC). METHODS: One hundred twelve patients with mild (G1), moderate (G2), and severe (G3) GED or diagnosed as indefinite for dysplasia were prospectively followed up with a standardized endoscopic and bioptic protocol. RESULTS: Evaluation of GED outcome refers only to 93 patients with a follow-up period longer than 12 months. Regression of dysplasia was documented in 36%, 27%, and 0% of G1, G2, and G3 GED cases, respectively. Progression to more severe dysplasia or evolution into GC was detected in 21%, 33%, and 57% of G1, G2, and G3 GED cases, respectively. Evolution into GC was documented for all grades of dysplasia and correlated significantly with high-grade atrophic gastritis. A high prevalence of early GC (86.9%) was also observed. CONCLUSIONS: GED is a pre-invasive lesion, and carcinomatous evolution increases proportionally with its histological grade. Bioptical follow-up is mandatory for all histological grades of GED and significantly increases the likelihood of GC being detected in its early stages.

Pathology and ploidy in the prognosis of gastric cancer with no extranodal metastasis.

BACKGROUND: The prognostic relevance of morphology in advanced gastric cancer is well known. Data on tumor cell DNA content are still inadequate and contradictory. METHODS: Morphologic parameters and DNA ploidy were evaluated in 76 gastric cancer patients with no extranodal metastases (Stage I, 10 cases; Stage II, 20 cases; and Stage III, 46 cases), using formalin-fixed paraffin-embedded tissue. All cases were followed for at least 6 years after surgery or until death. RESULTS: Among the potential prognostic factors analyzed by Mantel-Cox and generalized Wilcoxon statistics, male sex (P = 0.02), cardiac location of neoplasia (P = 0.02), deeper infiltration of the gastric wall (P = 0.001), vascular neoplastic invasion (P = 0.006), metastatic lymph nodes (P = 0.001), pathologic stage (P = 0.0001), and aneuploidy (P = 0.01) were significantly associated with lower survival rate. Testing of all of the above-mentioned variables by the Cox stepwise multiple regression model disclosed that factors independently associated with survival were stage (P = 0.0001), ploidy (P = 0.0006), and vascular carcinomatous invasion (P = 0.01). CONCLUSIONS: In gastric cancer with no extranodal metastases, DNA ploidy was found to be the most significant prognostic parameter after pathologic stage.

Nuclear DNA content and pathology in radically treated pancreatic carcinoma. The prognostic significance of DNA ploidy, histology and nuclear grade.

BACKGROUND: Nuclear DNA content and pathology are considered to be prognostically relevant in several solid tumors, but controversial findings have emerged in pancreatic carcinoma (PC). Histopathology and DNA ploidy were each correlated with survival in radically treated PC to ascertain the hierarchy of their prognostic significance. METHODS: DNA ploidy was assessed by flow cytometry (FC) in neoplastic tissue samples from 60 patients with PC who were followed until death. Representative neoplastic areas were obtained by microdissection from archival paraffin embedded material (excluding any carcinoma with a coefficient of variation of the G0/G1 peak higher than 8%). Histologic data and FC patterns were related to prognostic behavior using univariate multivariate statistical analysis. RESULTS: Aneuploid cancers were detected in 39 of 60 patients. Univariate analysis showed that histologic grade, nuclear grade, and ploidy were significantly related to prognosis. On multivariate analysis, only histologic grade and DNA ploidy (diploid vs. aneuploid) were significant with significant interaction. CONCLUSIONS: The prognostic value of pathology and ploidy was demonstrated in patients treated radically for PC. As in other tumors characterized by a short survival, the clinical usefulness of any prognostic parameters is somewhat limited. However, the significant relationship between prognosis and DNA ploidy might be of interest in a cost-benefit analysis for selecting patients in whom an attempt at radical surgical treatment or adjunctive chemotherapy may be justified.

Hepatoblastoma: DNA nuclear content, proliferative indices, and pathology.

Hepatoblastoma (HB) is the most frequent malignant liver tumor in infancy, and both its biological features and its prognostic behavior are still under investigation. DNA content and proliferative activity of the tumor have been considered as biological parameters related to the tumor's aggressiveness. The present study attempts to investigate the possible association between histologic subtype, DNA content, and proliferative indices in HB. DNA content and the proportion of cells in the S-phase were assessed by flow cytometry in 34 cases of HB (14 prior to chemotherapy, 20 after chemotherapy), using formalin-fixed, paraffin-embedded archival samples. The proliferative cell nuclear antigen (PCNA) labeling index was also evaluated by immunohistochemistry, and both the flow cytometry (FC) and the immunohistochemical data were correlated with tumor pathology. A significant association was found between histological type, DNA content and the percentage of cells in the S-phase, with aneuploidy and the highest proportions of S-phase cells significantly associated with embryonal tumors. The PCNA labeling index was found to be significantly higher in embryonal than in fetal phenotype. The biological heterogeneity of HB is Confirmed by the different nuclear content of the fetal (diploid) and embryonal (aneuploid) epithelial components of the tumor, also ruling out the likelihood of fetal (diploid) clones deriving from the embryonal (aneuploid) neoplastic cells. Since the highly proliferative neoplastic clones (i.e., embryonal) are thought to be more sensitive to antimitotic drugs, further studies are indicated to determine the relationship between ploidy, proliferative indices and chemoresponsiveness.