In recent years, the incidence of cervical adenocarcinoma has increased. The role of human papillomavirus (HPV) infection in cervical carcinoma is well established. The aim of this study was to investigate the possible correlation between the expression of cell cycle-associated proteins and HPV infection in cervical adenocarcinomas. We analyzed the expression of p16, p53, and Ki-67 in 68 cases of in situ and invasive cervical adenocarcinomas by immunohistochemistry. These cases were divided into high and low expression groups based on immunohistochemical staining data. High p16 expression was seen in 29 of 30 (96%) HPV-DNA-positive cases shown to be HPV-DNA positive by polymerase chain reaction (PCR), and in 26 of 27 (96%) cases shown to be HPV-DNA positive by in situ hybridization (ISH) . In 50 cases of stage I b and stage II adenocarcinomas, statistical analysis showed a highly significant differences between the high expression of p16 and the HPV-positivity by ISH (P=0.003) and PCR (P=0.001) . High expression of Ki-67 also showed a strong relation with HPV-Positivity by ISH (P=0.002) . Patients in whom a high expression of p16 was observed had a lower recurrence rate than patients with a low expression of p16 (P=0.028) . Cases with a high expression of Ki-67 showed a better prognosis than those with a low expression of Ki-67 (P=0.024) . P16 and Ki-67 are useful biomarkers for HPV-DNA-positive cervical adenocarcinomas, which are easily monitored by immunohistochemical staining.

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The tumor suppressor gene, maspin inhibits invasion, metastasis, and angiogenesis of cancers. In this study, we examined maspin expression patterns in early lesions of gastric carcinoma and their relevance to disease progression by examining gastric adenoma and early gastric carcinoma (e.g., intramucosal carcinoma and sub-mucosal carcinoma) . Immunohistochemical staining detected maspin expression in adenoma (24 patients), intra-mucosal carcinoma (56 patients), and sub-mucosal carcinoma (57 patients) . While maspin expression was rarely observed in normal mucosa remote from the carcinoma, the percentage of maspin-positive cells in normal mucosa and in intestinal metaplasia adjacent to carcinoma was 93.9%. In the adenoma samples, 96.0% expressed maspin. Although the percentage of tumor cells expressing maspin was as high as 82.1% in intra-mucosal carcinoma and 75.4% in sub-mucosal carcinoma, it was still lower than in intestinal metaplasia and adenoma. Vascular invasion occurred at a significantly lower frequency when maspin expression was detected in the area of sub-mucosal invasion. These results suggested that maspin is involved in gastric carcinoma progression even at an early stage, and that maspin expression in the infiltration area is likely to influence the prognosis.

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The objective of this study was to immunologically and nutritionally evaluate infants with a high risk of atopic disease using a new partially hydrolyzed formula (PHF) . One hundred and fifty neonates with a family history of atopic disease were randomly divided into 2 groups and mother's milk was supplemented with PHF or a conventional milk formula (CMF) . The study period was 6 months after birth and immunology, the presence or absence of allergic symptoms and growth were evaluated. The infants (n=140) were followed for 6 months after birth. The infants were divided into 3 groups ; PHF-mixed nutrition group (PHF group, n=77), CMF-mixed nutrition group (CMF group, n=37), and complete mother's milk nutrition group (MM group, n=26) . No significant differences were noted in the serum total IgE or milk-specific IgE levels at 1 and 6 months of age among the 3 groups. None of the infants was positive for milk-specific IgG4 at 6 months of age in the PHF group, but 8 (22%) and 2 (8%) infants were positive in the CMF and MM groups, respectively. Levels were significantly lower in the PHF group than in the CMF group (P<0.001) . There were no significant differences in the incidences of atopic disease, growth or development among the 3 groups. The rate of appearance of serum milk-specific IgG4 subclass was lower at 6 months after birth in the PHF group than in the CMF group, suggesting that milk antigenicity of PHF was low.

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The aim of this study was to examine the effects of smoking on changes in cardiovascular disease risk factors between childhood and young adulthood. Blood pressure, serum lipoproteins and body mass index were measured in 2258 individuals ; as children in 4 baseline surveys (1974-1977) and as young adults in 3 follow-up surveys (1985-1996), in the biracial community of Bogalusa, Louisiana. Smoking variables were defined as categories based on (1) present smoking status, (2) cumulative smoking volume (pack-years ever smoked), and (3) years since quitting smoking. We found that in heavier smokers there was a significantly greater increase in low-density lipoprotein cholesterol and serum triglycerides, and a decrease in high-density lipoprotein cholesterol. These changes showed appropriate dose-response gradients. The length of time individuals remained smoke-free was related to significantly smaller increases in blood pressure and serum triglycerides (in both sexes), and to an increase in body mass index in males only. These findings support the use of pack-years as an appropriate indicator for evaluation of changes in risk factor variables. The results suggest that even in young adulthood, smoking causes adverse changes in the risk factors for cardiovascular disease, and that quitting smoking earlier brings about beneficial changes.

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Proton pump inhibitors (PPIs) are substituted benzimidazoles, which are unstable at a low pH. We hypothesized that rapid transit of a PPI to the upper small intestine has some benefit in PPI therapy. Mosapride citrate, a 5-hydroxytryptamine 4 receptor (5-HT₄) agonist, has a profound effect on facilitating gastric motility. The aim of this study was to examine the effect of mosapride citrate on the pharmacokinetics of omeprazole. Eleven healthy volunteers were enrolled. After overnight fasting, 20 mg of omeprazole was given orally and plasma samples were obtained before and after 1, 2, 3 and 4 hours of dosing. Two weeks later, 5 mg of masapride citrate was given one hour before administration of 20 mg of omeprazole and plasma samples were obtained at the same time intervals as above. The plasma concentrations of omeprazole were determined by high performance liquid chromatography. Pharmacokinetic parameters, including the peak plasma concentration (Cmax), the time to reach Cmax (Tmax) and the area under the time-concentration curve during four hours of dosing (AUC4) were used for statistical analyses. Data from 10 out of 11 subjects was available. The Tmax was shifted from 2.22±0.44 h (mean±SD) to 1.66±0.50 h by mosapride citrate (P<0.05) . The Cmax increased from 363.5±293.3 ng / ml to 527.4±233.0 ng / ml in the presence of mosapride citrate (P<0.01) . The AUC4 was 632.0±183.3 ng h/ml and 1041.3±450.8 ng h/ml in the absence and presence of mosapride citrate, respectively (P<0.05) . Conclusions. Mosapride citrate beneficially affected pharmacokinetics of omeprazole probably by accelerating gastric motility.

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Protease-activated receptors (PARs) are a family of GTP-binding protein-coupled receptors activated by serine proteases. PAR-2 is distributed throughout the gastrointestinal system including the pancreas and may be involved in the inflammatory process of pancreatitis. It is uncertain whether pancreatic PAR-2 plays a protective or an injurious role in acute pancreatitis. The aim of this study is to elucidate the role of PAR-2 in acute pancreatitis in a rat model. We induced mild pancreatitis by using caerulein to induce acute edematous pancreatitis (AEP) and severe pancreatitis by using DL-ethionine and a protein-deficient meal to induce acute necrotizing pancreatitis (ANP) . Nafamostat mesilate (NM) (3 or 10mg/kg) was injected intraperitoneally to the AEP rats every 12 hours to investigate the effects of protease inhibitor on pancreatitis and PAR-2 activation. Camostat mesilate (CM) (200mg/kg) was orally administered to ANP rats every 24 hours. Immunoreactive PAR-2 was most prominent in ED1-positive macrophages l monocytes in ANP and infiltration of PAR-2-positive macrophages was significantly inhibited by CM (200mg) . PAR-2-positive macrophages / monocytes were observed in AEP. Plasma IL-8 levels increased in ANP and were inhibited by CM. Amylase secretion from acinar cells was elicited in a dose-dependant manner by SLIGRL-NH2, an amino-terminal residue of PAR-2-tethered ligand, indicating that PAR-2 may exist in acinar cells and may mediate amylase secretion. Studies in vivo indicate that the PAR-2 system of macrophages / monocytes is activated and involved in the exacerbation of acute pancreatitis, presumably via release of cytokines such as IL-8. Studies in vitro indicate that PAR-2 may exist in acinar cells in normal rat pancreas and function physiologically.

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