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Biomedical subjects

M Rugge

Publications and source records attributed to M Rugge.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Phenotypic changes in mucin-secreting cells in the ileal neobladder mucosa: a metaplastic or precancerous lesion?].

Colonic metaplasia with shifting from sialo-to sulfomucins was observed in 10/18 patients with ileal orthotopic neobladder; their median follow-up was 59 months. There is a significant statistical relationship (p = 0.002) between Colonic Metaplasia and a follow-up longer than 14 months. Diversion Cancer is nowadays a practical problem and probably urologists will be confronted with it in the future more than at present. A modification of established attitudes as regards urinary diversion in standard situations (i.e., 60 over years old patients with invasive bladder cancer) don't seems, at present, justified, although our study confirms the suspicion that ileal neobladder could be considered theoretically at risk for cancer onset.

Aged↗
PubMed1998

Prompt hepatitis C virus suppression following hepatitis B virus superinfection in chronic untreated hepatitis C.

The natural course of chronic hepatitis C virus infection after hepatitis B virus superinfection is not clear since it is difficult to determine the chronology of the double infections. We report on a case of de novo hepatitis B virus infection in the course of chronic untreated hepatitis C, in which the time of hepatitis B virus infection is actually known. The patient eliminated HCV-RNA, both from serum and from liver tissue, soon after the clinical onset of the acute hepatitis B. Liver histology featured hepatitis with severe portal inflammation and high-grade periportal and intralobular necro-inflammatory lesions. This observation demonstrates that hepatitis C virus replication can be promptly and spontaneously suppressed by acute hepatitis B virus superinfection.

Acute Disease↗
PubMed1997

Hepatic stellate cell immunodetection and cirrhotic evolution of viral hepatitis in liver allografts.

Patients with chronic viral hepatitis are at high risk of developing cirrhosis, but the outcome of the disease in a given patient is unpredictable. Hepatic stellate cells have been demonstrated to be the most important cell type involved in hepatic fibrogenesis, regardless of the cause of the liver injury. The alpha isotype of actin (a phenotypic marker of smooth muscle cells) may be expressed by hepatic stellate cells, reflecting their "activation" to myofibroblast-like cells. The present study aimed to analyze the expression of alpha-smooth muscle actin-positive hepatic stellate cells in liver allografts with recurrent viral hepatitis, and to evaluate whether and how such expression may be related to the outcome of the disease. Using immunohistochemistry and a semi-quantitative scoring system, the expression of a-smooth muscle actin in hepatic stellate cells was analyzed in liver allografts of 17 patients with recurrent viral hepatitis. They included nine patients who developed cirrhosis at the end of follow-up (mean time 23.6 months), and eight patients with no cirrhosis at the end of a comparable follow-up time (mean 30.1 months). In all patients, liver biopsy specimens were obtained between 3 and 6 months (t1) and between 10 and 15 months (t2) after transplantation. Preperfusion biopsy specimens of donor livers served as a baseline (t0). By comparison with the baseline biopsy, an increased number of alpha-smooth muscle actin-expressing hepatic stellate cells was observed in all cases in t1 biopsies. An increase in the amount of alpha-smooth muscle actin-positive hepatic stellate cells in zone 1 at t1 was significantly (P < .006) related to subsequent cirrhotic evolution. In conclusion, in liver allografts with recurrent viral hepatitis, the activation of hepatic stellate cells is an early event. An increased number of alpha-smooth muscle actin-positive hepatic stellate cells in zone 1 may represent an unfavorable event related to cirrhotic evolution.

Actins↗
PubMed1997

bcl-2 and p53 immunophenotypes in pre-invasive, early and advanced oesophageal squamous cancer.

AIMS: An inverse correlation between bcl-2 and p53 expression has been reported in several types of epithelial tumour. The role of bcl-2 and p53 in the development of oesophageal squamous carcinoma has yet to be established. The expression of bcl-2 and p53 proteins has been evaluated in the multistage oesophageal tumorigenesis, which progresses from normal mucosa to dysplasia (squamous intraepithelial lesion, SIL), to invasive early and advanced oesophageal squamous cancer. METHODS AND RESULTS: Sixty-four cases of squamous oesophageal cancer, coexisting with SIL in 18 cases, were immunohistochemically analysed for any overexpression of bcl-2 and p53 proteins. Any association of bcl-2 and p53 protein expression with patient survival was also analysed. We observed bcl-2 expression that decreased significantly during the progression of oesophageal carcinogenesis. A decreasing frequency in the expression of bcl-2 in advanced oesophageal squamous cancer coincided with frequent p53 overexpression. bcl-2 expression was correlated with patient survival by univariate analysis. The association disappeared after adjusting for tumour stage, p53 overexpression showed no association with patient survival by either univariate or multivariate analysis. CONCLUSIONS: The down-regulation of bcl-2 and upregulation of p53 in advanced oesophageal squamous cancer suggest that bcl-2 and p53 proteins may interact in the progression of oesophageal squamous cancer.

Adult↗
PubMed1997

p53 alterations but no human papillomavirus infection in preinvasive and advanced squamous esophageal cancer in Italy.

Geographic differences in exposure to suspected carcinogens have been identified in esophageal carcinogenesis, and both p53 alterations and human papillomavirus (HPV) infection have been reported in esophageal squamous carcinoma (ESC) from high-risk areas, including China and South Africa. The status of p53 alterations and HPV infection in ESC has not been determined in northern Italy, where the incidence of ESC is low. Formalin-fixed paraffin-embedded esophageal samples containing normal, dysplastic, and carcinomatous tissue from 18 patients were examined for p53 protein accumulation with immunohistochemistry, p53 mutation (exons 5-8) with PCR-single-strand conformation polymorphism analysis and DNA sequencing, and HPV infection with PCR using general primers to amplify the L1 gene. Accumulation of p53 protein was observed in both precancerous and carcinomatous lesions. p53 mutations were rare in dysplastic lesions but were detected in 9 of 18 carcinomas, a finding consistent with reports from other geographic areas. Examination of the p53 mutation spectrum revealed no hot spot mutation. In contrast, HPV was not found in any of these 18 cases. This is consistent with the findings from other low ESC risk areas in which HPV infection may not play a crucial role in esophageal oncogenesis, whereas the high risk of ESC in China and South Africa may be attributed to frequent HPV infection.

Aged↗
PubMed1997

Chronic atrophic gastritis and Helicobacter pylori infection in primary biliary cirrhosis: a cross-sectional study with matching.

BACKGROUND/AIMS: Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by exocrine gland impairment. Up to now there have been no reports dealing with gastric mucosa involvement in this autoimmune condition, which is frequently associated with Sjögren's syndrome. The aim of this study was to investigate the morphologic, biochemical and immunological features of the gastric mucosa in PBC. METHODS: A cross-sectional study with matching was performed. Thirty-three PBC patients (30 F, 3 M, mean age 58 years; 17 with stage II-III, and 16 with stage IV disease) and 33 sex- and age-matched dyspeptic controls were included. Six biopsy specimens from the fundus (2), body (2) and antrum (2) were taken from all patients and controls. A serological assessment was performed for each subject, i.e. pepsinogen A (PGA), pepsinogen C (PGC), gastrin (G), and antibodies against Helicobacter pylori (anti-Hp IgG). RESULTS: Endoscopic gastritis was found in 22 PBC patients (66.6%). There was no difference between PBC patients and controls regarding the percentage of subjects with mild, moderate, severe or atrophic gastritis (AG). There was no difference in gastric mucosal involvement between PBC subjects with or without secondary Sjögren's syndrome. A discrepancy was observed in the data obtained with respect to Helicobacter pylori (H. pylori) infection. H. pylori colonization was significantly more frequent in controls than in PBC patients (79% vs 49%, p < 0.002), but anti-Hp IgG were detected in the same percentage in the two groups (90% vs 83% respectively). There was no difference between the two groups in the PGA, PGC, PGA/PGC ratio, or gastrin. Eight PBC patients had esophageal varices. CONCLUSIONS: PBC patients are not characterized by chronic atrophic gastritis. Even though they present chronic gastritis with the same prevalence as dyspeptic controls, and show signs of previous H. pylori infection as frequently as dyspeptic patients, they are actually much less frequently infected. The reasons for this observation are unclear.

Adult↗
PubMed1996

Potential gastrointestinal tumor suppressor locus at the 3p14.2 FRA3B site identified by homozygous deletions in tumor cell lines.

A number of DNA fragments, identified by representational difference analysis, which were homozygously deleted in various cancer cell lines were previously mapped to human chromosomal arms. One of these, BE758-6, which was homozygously deleted in a number of colon carcinoma cell lines, had been mapped to chromosome region 3p. We have further localized the probe to 3p14.2, approximately 350kbp telomeric to the 3p14.2 break of the t(3;8) hereditary renal cell carcinoma chromosome translocation, within or near the 3p14.2 FRA3B, the most common human fragile site. We determined the sizes of the homozygous deletions in a number of cancer cell lines after isolation of a yeast artificial chromosome contig and development of STS markers which fall between D3S1234 and D2S1481, which flank the deletions. Homozygous deletions were observed and sized not only in the cell lines originally reported but also in a number of nasopharyngeal carcinoma cell lines and a gastric carcinoma cell line. About 50% of uncultured stomach and colon carcinomas were then shown to lose heterozygosity for alleles in the same region, with a common region of loss between the D3S1234 and D3S1481 markers. Thus, it is likely that the homozygous deletion observed in these cancer cell lines harbors an important tumor suppressor gene for several tumor types.

Base Sequence↗
PubMed1996

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.

Adult↗
PubMed1996

Loss of heterozygosity for chromosome 11 in adenocarcinoma of the stomach.

Loss of heterozygosity (LOH) at several chromosomal loci is a common feature of the malignant progression of human tumors. In the case of chromosome 11, LOH has been well documented in several types of solid neoplasms, including gastric carcinoma, suggesting the presence of suppressor gene(s) at 11p15 and 11q22-23. Little is currently known about the molecular events occurring during the development of gastric cancer. To define the regions of chromosome 11 involved in gastric cancer progression, we used high-density polymorphic markers to screen for LOH in matched normal and tumor tissue DNA from 60 primary gastric carcinomas. We found that 21% of the tumors showed LOH simultaneously at 11p15 and 11q22-23, 41% had LOH at 11p15, and 30% had LOH at 11q22-23. We confirm that the minimal critical area of LOH for 11p15.5 is the approximately 2-Mb region between loci D11S1318 and D11S988. However, when we analyzed the pattern of LOH according to the country of origin of the patient, LOH for 11q22-23 alone was found only in cases from Italy. The minimal critical region of LOH at 11q22-23 is identical to that identified for other solid tumors, suggesting that the same putative tumor suppressor gene(s) contained within this region is involved in the pathogenesis of several common human tumors.

Adenocarcinoma↗
PubMed1996

Helicobacter pylori in promotion of gastric carcinogenesis.

Gastric atrophy and intestinal metaplasia are considered the earliest phenotypic changes in the cascade of events leading from normal mucosa to intestinal-type gastric cancer, and epidemiological evidence links Helicobacter pylori to gastric epithelial malignancies. To evaluate any causal relationship between bacterial infection and atrophic metaplastic lesions, gastric pathology was histologically and histochemically evaluated in 267 consecutive, nonulcerous, untreated subjects, with attention given the phenotypes of intestinal metaplasia. The prevalence of Helicobacter pylori infection was 61%. Intestinal metaplasia (particularly types II and III) was significantly associated with both Helicobacter pylori detection (chi 2 LR: P < 0.002) and increasing age (chi 2 LR: P < 0.002). Using logistic regression analysis, the development of intestinal metaplasia proved more significantly linked with Helicobacter pylori infection [odds ratio = 4.55 (95% confidence interval: 1.51-13.7)], than with age [odds ratio = 1.03 (95% CI: 1.01-1.06)], with no interaction. In conclusion, Helicobacter pylori can be considered among the major causal agents of mucosal lesions involved in the multistep process of gastric carcinogenesis, justifying any attempt to eradicate this bacterial infection.

Adolescent↗
PubMed1996

Helicobacter pylori infection enhances mucosal interleukin-1 beta, interleukin-6, and the soluble receptor of interleukin-2.

It is thought that Helicobacter pylori colonization of the gastric mucosa might stimulate the production of several cytokines, which might trigger and maintain the gastric inflammation associated with Helicobacter pylori infection. In the present study we evaluated interleukin-1 beta. interleukin-6, and the soluble receptor of interleukin-2 both in mucosal homogenates and in the sera of Helicobacter pylori-infected (39 cases) and uninfected (40 cases) patients to investigate whether there was any relationship between variations in cytokines and (1) the severity of Helicobacter pylori-associated gastritis or (2) CagA-positive Helicobacter pylori strains. Mucosal, but not serum levels of interleukins-1 and -6 and interleukin-2 receptor were significantly higher in infected than uninfected patients. Serum levels of Helicobacter pylori antibodies were significantly higher in infected than uninfected patients. These levels correlated with mucosal interleukin-1 beta. The degree of antral or body inflammatory grade was higher in infected than in uninfected patients; cytokines levels were higher in patients with high-grade gastritis, most of whom were Helicobacter pylori positive. Patients infected with CagA-positive strains also had higher levels of interleukin-1 beta, but not of interleukin-2 receptor or interleukin-6. In conclusion. Helicobacter pylori infection results in a local increase in interleukins-1 beta and -6 and interleukin-2 receptor associated with high-grade mucosal inflammation. Interleukin-1 beta seems to favor anti-Helicobacter pylori antibody production, and mucosal levels are enhanced mainly in patients infected with cytotoxic Helicobacter pylori strains.

Adult↗
PubMed1996

Serum procollagen type III peptide in chronic hepatitis B. Relationship to disease activity and response to interferon-alpha therapy.

The clinical significance of serum procollagen type III peptide, a marker of active fibrogenesis, was evaluated in 110 hepatitis B surface antigen positive patients with chronic hepatitis (32 chronic persistent hepatitis, 60 chronic active hepatitis, and 18 active cirrhosis), selected on the basis of active viral replication and biochemical activity, including 54 cases treated with interferon-alpha. At presentation the procollagen type III peptide level serum was above normal in 48 (44%) of the 110 patients and the median value was significantly higher than that of healthy carriers with normal transaminases and histology (P < 0.000005). Semiquantitative histological evaluation showed a significant correlation between serum procollagen type III peptide levels and necrosis/inflammation in the subgroup of patients with chronic active hepatitis, but no relationship with the score of fibrosis. Among patients treated with interferon-alpha and with increased fibrogenic activity (indicated by high pretreatment serum levels of procollagen type III peptide), peptide levels were significantly decreased when pretreatment levels were compared with those at 12 months after therapy withdrawal, both in responders to interferon (P = 0.022) and non-responders (P = 0.012). However, serum procollagen type III peptide levels normalized in 75% of responders to interferon with sustained serological and histological remission of liver disease, but in only 21% of non-responders (P = 0.02). These results obtained in a well-defined population suggest that serum procollagen type III peptide is a better marker of active fibrogenesis and inflammation than an indicator of the extent of fibrosis, and that interferon may reduce active liver fibrogenesis in chronic hepatitis B independently of its effect on viral replication. However, a consistent proportion (56%) of our chronic hepatitis B patients had normal serum procollagen type III peptide levels at presentation, thus precluding the clinical use of this marker both for diagnosis of liver injury and for monitoring the therapeutic response to interferon.

Adult↗
PubMed1996

Liver stellate cells in chronic viral hepatitis: the effect of interferon therapy.

BACKGROUND/AIMS: Liver stellate cell proliferation and differentiation into myofibroblast-like cells is related to the development of liver fibrosis. Several cytokines, including interferons, regulate liver stellate cell proliferation and phenotypic modulation. Recent studies indicate that human liver stellate cells express the alpha-isotype of actin, specific to smooth muscle cell differentiation. We aimed to evaluate the expression of alpha-smooth muscle actin-positive liver stellate cells in patients with chronic viral hepatitis and to evaluate whether and how such expression can be modified by alpha-interferon treatment. METHODS: Using immunohistochemistry, and a semi-quantitative scoring method, we evaluated alpha-smooth muscle actin expression in liver stellate cells before and after alpha-interferon therapy in a series of liver biopsies from 44 patients with chronic viral hepatitis. RESULTS: Before therapy, a large number of liver stellate cells expressing alpha-smooth muscle actin were present throughout all acinar zones. A significant reduction in alpha-smooth muscle actin expression by liver stellate cells was demonstrated in biopsies performed after suspending the interferon treatment. The drop in the number of alpha-smooth muscle actin-labelled cells after therapy correlated closely with the improvement in the histological index of activity. CONCLUSIONS: The results suggest a specific effect of interferon on liver stellate cells, possibly related to its anti-inflammatory action.

Actins↗
PubMed1996

Increased levels of cathepsin B and L, urokinase-type plasminogen activator and its inhibitor type-1 as an early event in gastric carcinogenesis.

BACKGROUND: Cysteine proteases [cathepsin B (CATB), cathepsin L (CATL)], the serine protease urokinase-type plasminogen activator (UPA) and its inhibitor type-1 (PAI-1) play an important part in cancer invasion. No data are available on the relationship between these proteases and gastric precancerous changes. AIMS: To determine CATB, CATL, UPA, PAI-1 in chronic atrophic gastritis, intestinal metaplasia and gastric epithelial dysplasia, as precancerous changes, and to compare these data with those obtained in gastric cancer. PATIENTS: Endoscopic biopsies were obtained from 12 patients with gastric cancer (cancerous tissue), 33 patients with chronic atrophic gastritis (all with intestinal metaplasia and 12 with dysplasia) and from 47 control subjects, for a total of 92 patients. METHODS: Antigen concentrations were measured using ELISA methods. Immunohistochemistry was performed using monoclonal anti-CATB and anti-PAI-1 antibodies. RESULTS: CATB, CATL, UPA and PAI-1 were significantly higher in chronic atrophic gastritis than in controls (CATB: P < 0.001; CATL: P < 0.005; UPA: P < 0.000001; PAI-1: P < 0.005). The same was observed for cancer. CATB and UPA were significantly higher in chronic atrophic gastritis, with versus without dysplasia (P < 0.05). Dysplastic epithelia showed strong immunoreactivity to PAI-1 and CATB. CONCLUSIONS: Our study demonstrates that cathepsins, UPA and PAI-1 may have a role not only in the process of cancer invasion, but also in the progression of precancerous changes into cancer.

Adult↗
PubMed1996

Gastric antioxidant, nitrites, and mucosal lipoperoxidation in chronic gastritis and Helicobacter pylori infection.

We have evaluated gastric juice pH, nitrites and vitamin C levels, mucosal glutathione, and malondialdehyde, a marker of lipid peroxidation, in patients with chronic gastritis undergoing endoscopy. Patients had chronic gastritis with (n = 28) or without (n = 60) atrophy and/or concomitant Helicobacter pylori infection. Nineteen healthy subjects, without major macroscopic or histologic changes, were included as controls. Ten subjects were studied before and after H. pylori eradication. Vitamin C levels were low in atrophic gastritis (p < 0.006) and H. pylori infection (p < 0.02). Nitrite concentrations and pH were significantly higher in atrophy (p < 0.005 and 0.0001). Glutathione turnover was higher than normal in gastritis, with higher levels of oxidized glutathione (p < 0.02). Gastric malondialdehyde levels were significantly increased by gastritis (p < 0.05) and H. pylori infection (p < 0.05). Overall, more active gastritis coincided with lower vitamin C levels and higher malondialdehyde levels. After H. pylori eradication a drop in mucosal MDA levels was observed (p = 0.04). In summary, chronic gastritis and H. pylori infection correlate with increased free-radical production, reduced gastric vitamin C levels, and increased glutathione turnover. The possible implications of these changes in the pathogenesis of gastric damage and in carcinogenesis are intriguing.

Adult↗