Biomedical subjects

C Vindigni

Publications and source records attributed to C Vindigni.

At least 37 records · Page 2Linked to original sources

PubMed1999

Hematopoietic cancer and peptic ulcer: a multicenter case-control study.

Helicobacter pylori has been suggested as a cause of gastric carcinoma and gastric non-Hodgkin's lymphoma (NHL). In a previous cohort study, a relative risk of six for gastric NHL was reported among subjects who tested positive for anti-H.pylori antibodies. The association between peptic ulcer and NHL has been studied in a population-based case-control investigation on hemato-lymphopoietic malignancies in Italy, based on face-to-face interviews to 2671 cases and 1718 controls (refusal rates 10 and 19%, respectively). Subjects who reported a diagnosis of peptic ulcer had a relative risk of 5.6 [95% confidence interval (CI) 3.8-8.0] for gastric NHL, whereas the estimate for non-gastric NHL was 1.3 (1.0-1.6). The association with recent diagnosis of ulcer was stronger, but the odds ratio (OR) was as high as 2.1 (95% CI 1.1-4.2) after >/=20 years since such diagnosis. After exclusion of the last 2 years before the diagnosis of NHL, and of ulcers diagnosed before 1978 (when gastroscopy became common in Italy), the OR was still 5.3 (95% CI 3.0-9.2). We found a strong effect modification by educational level, with ORs for ulcer more elevated in higher social groups. Gender was an effect modifier (OR = 4.1 in males, 9.2 in females; P = 0.03 for heterogeneity). The association with other gastrointestinal pathologies was much lower and statistically not significant. Almost all gastric lymphomas were B-cell NHLs of intermediate grade according to the working formulation; the majority belonged to the mucosa-associated lymphoid tissue (MALT) type. The association with ulcer was much stronger among MALT lymphomas, but only for recent ulcer diagnoses (2-10 years). Our study shows an increased risk for gastric NHL, very similar to the estimate reported in a previous cohort study. The risk was higher among more educated subjects.

Adult↗

PubMed1998

Most Helicobacter pylori-infected patients have specific antibodies, and some also have H. pylori antigens and genomic material in bile: is it a risk factor for gallstone formation?

Bile may contain a 130-kDa protein endowed with aminopeptidase activity and the ability to promote cholesterol crystallisation. As >90% of H. pylori strains have a similar peptidase activity, and half the isolates express a 110- to 140-kDa antigen, the CagA protein, we investigated a possible association between H. pylori infection and gallstones, and the presence in bile samples of factors related to H. pylori that could increase cholesterol crystallization. The prevalence of H. pylori infection was 82.1% in 112 patients with gallstones and 80.3% in 112 controls (NS). Fifteen bile samples out of 23 specimens from infected patients (65.2%) contained anti-CagA antibodies. A approximately 60-kDa antigen only reacting with an anti-CagA antibody was found in five bile samples (21.7%) from 23 infected patients. One bile sample (4.1%) contained ureA and cagA genes of H. pylori. The homology of CagA with the N-terminal sequence of aminopeptidase N was very low. We concluded that the presence of specific antibody to H. pylori in most bile samples tested and of an H. pylori putative antigen in a discrete number of cases may represent factors that increase the risk of gallstone formation.

Antibodies, Bacterial↗

PubMed1998

cagA positive and negative Helicobacter pylori strains are simultaneously present in the stomach of most patients with non-ulcer dyspepsia: relevance to histological damage.

BACKGROUND/AIMS: Infection with Helicobacter pylori strains harbouring the cagA gene (cagA+) is associated with an increased risk of developing peptic ulcer and gastric cancer. The aim of this study was to assess whether H pylori isolates with different cagA status were present in patients with non-ulcer dyspepsia, and whether a variable cagA status is relevant to histological gastric mucosal damage and glandular cell proliferation. METHODS: Well separated H pylori colonies (between 2 and 25) from primary plates, per gastric area, for each of 19 patients with non-ulcer dyspepsia were examined for cagA by hybridisation. Western blotting was used to examine both representative colonies for CagA expression and the patients' sera for antibody response to CagA. Glandular gastric cell proliferation was assessed immunohistochemically. RESULTS: Of the 747 colonies examined, 45.3% were cagA+. All colonies from four patients were cagA+, and all colonies from two patients were cagA-. In 13 patients (68%) both cagA+ and cagA- colonies were found. CagA expression of isolates corresponded to their cagA status. H pylori strains with different CagA molecular masses were present in three patients. Results based on all 19 patients studied showed that the prevalence of cagA+ colonies in areas with mucosal atrophy associated or not with intestinal metaplasia (67.9%) was significantly higher than in normal mucosa (44.7%) and mucosa from patients with chronic gastritis (44.0%) (p < 0.001). High levels of cell proliferation were associated with histological atrophy with or without intestinal metaplasia, but not with the possession of cagA by organisms colonising the same mucosal sites. CONCLUSIONS: Most patients with nonulcer dyspepsia are infected by both cagA+ and cagA- H pylori colonies. The cagA status of infecting organisms may play a role in the development of atrophy and intestinal metaplasia.

Adult↗

PubMed1998

Cell kinetic patterns in early gastric cancer.

Early gastric cancers (EGC) may be subdivided into 2 groups by means of the use of mitotic index, apoptotic index and cell density: EGCs with high cell turnover and low cell density, which show high cell dissociation and, more frequently, lymph node invasion; EGCs with low cell turnover and high cell density. The same parameters discriminate among intestinal type tumors, when separately considered from diffuse ones. No correlation is noted of these 2 groups with transforming growth factor-alpha, epidermal growth factor receptor and p53 expression, gross type, entity of neoangiogenesis, and submucosal invasion.

Apoptosis↗

PubMed1998

New acquisitions in Helicobacter pylori characteristics.

The protection of Helicobacter pylori from the gastric acid exerted by urease is based on an increase of the bacterial periplasmic pH and membrane potential. Ammonia generated from urea induces apoptosis of gastric cells in vitro, and inhibits gastric somatostatin release in animals, which could have consequences on the physiology of digestion in general. The type s1/m1 structure of the vacA gene is associated with the production of high levels of cytotoxin. Strains with m2 region type, formerly considered devoid of toxic activity, are fully toxic when assayed with cell lines other than HeLa cells, which possibly lack receptors for m2 VacA type. The enhanced gastric mucosa damage associated with infection by cytotoxic organisms could be explained by the varying of effects exerted by VacA on target cells: extracellular secretion of acidic hydrolases, cytoskeletal alterations, actin rearrangement, reduction of epidermal growth factor binding to its receptor, inhibition of the stimulation of CD4+ T cells proliferation induced by the antigen presenting cells. Organisms that possess the pathogenicity island cag (cag+) induce an increased inflammation and transduction of signals to the host cells; however, they reduce the apoptosis of colonised cells. The results of an investigation on the possible influence of a variable cagA status on the extension of apoptosis have indicated that this kind of programmed death is disengaged from the possession of cagA by Helicobacter pylori organisms colonising the same gastric areas. It is likely that the whole pathogenic potential of cag+ organisms is far from being completely explored, as suggested by the recent finding that the expression of a bacterial adhesin (called BabA) involved in binding to the blood group antigen Lewis b is associated with the presence of cag.

Animals↗

PubMed1997

Cell proliferation, cell death and angiogenesis in early and advanced gastric cancer of intestinal type.

Mitotic (MI) and apoptotic index (AI), the sum of the 2, i.e., the turnover index (TI), tumor neovascularization (NV) and p53 expression, as well as tumor grading and node status, are evaluated in early and advanced gastric-cancer cases. T1 cases show significantly less frequent lymph-node invasion and lower tumor grade, and, taken together, have significantly lower MI, Al and TI and higher values of NV than the T2-3 cases. However, correlation of the variables shows that the above-mentioned discrimination is due to a minority of T1 cases (11 out of 33), while the majority of them are allocated in the same 95% ellipse of tolerance of the T2-3 cases.

Azure Stains↗

PubMed1997

Therapeutic intragastric vaccination against Helicobacter pylori in mice eradicates an otherwise chronic infection and confers protection against reinfection.

Chronic infection of the gastroduodenal mucosae by the gram-negative spiral bacterium Helicobacter pylori is responsible for chronic active gastritis, peptic ulcers, and gastric cancers such as adenocarcinoma and low-grade gastric B-cell lymphoma. The success of eradication by antibiotic therapy is being rapidly hampered by the increasing occurrence of antibiotic-resistant strains. An attractive alternative approach to combat this infection is represented by the therapeutic use of vaccines. In the present work, we have exploited the mouse model of persistent infection by mouse-adapted H. pylori strains that we have developed to assess the feasibility of the therapeutic use of vaccines against infection. We report that an otherwise chronic H. pylori infection in mice can be successfully eradicated by intragastric vaccination with H. pylori antigens such as recombinant VacA and CagA, which were administered together with a genetically detoxified mutant of the heat-labile enterotoxin of Escherichia coli (referred to as LTK63), in which the serine in position 63 was replaced by a lysine. Moreover, we show that therapeutic vaccination confers efficacious protection against reinfection. These results represent strong evidence of the feasibility of therapeutic use of VacA- or CagA-based vaccine formulations against H. pylori infection in an animal model and give substantial preclinical support to the application of this kind of approach in human clinical trials.

Animals↗

PubMed1997

Intestinal histological and ultrastructural inflammatory changes in spondyloarthropathy and rheumatoid arthritis.

To determine the prevalence of morphologic bowel lesions in patients with inflammatory rheumatic diseases and to better define the interactions between intestinal and articular pathology, 177 patients [39 with reactive arthritis (ReA), 40 with psoriatic arthritis (PsA), 23 with ankylosing spondylitis (AS), 21 with undifferentiated spondyloarthropathy (USpA) and 54 with rheumatoid arthritis (RA)] underwent ileocolonoscopy followed by multiple biopsies of the large bowel and the ileum and ileocecal valve. Biopsies were then examined with light and electron microscopy. During the endoscopic examination various degrees of gut inflammation were observed in 13% of ReA, 5% of PsA, 26% of AS, 14% of USpA and 11% of RA patients. At the histological examination those percentages were respectively 51%, 45%, 48%, 38%, and 15%, and at the electron microscopic examination 76%, 53%, 90%, 60%, and 50%. Our results show that an involvement of the gut is a factor in a large percentage of patients with spondyloarthropathy and, to a lesser extent, with RA. The involvement of the intestine in RA manifests itself mainly in ultrastructural lesions, thus this involvement is not so obvious as in the spondyloarthropathies; however, it could nonetheless play an important role in the etiopathogenesis of this disease.

Adolescent↗

PubMed1996

Incidence rates of leukemias, lymphomas and myelomas in Italy: geographic distribution and NHL histotypes.

The annual incidence of non-Hodgkin's lymphomas is increasing by 3 to 4% in different parts of the developed world, while rates for Hodgkin's disease, myelomas and leukemias are more stable. In the case of this group of malignancies, hypothesis generation on risk factors has been limited by the use of the ICD classification in mortality and incidence statistics. We have computed incidence rates in different Italian areas after careful re-classification of diagnoses, and considering specific histotypes (Working Formulation for NHL, Rye's classification for HD). While no particularly interesting pattern is suggested for Hodgkin's disease (even after considering specific Rye subgroups), multiple myeloma and leukemias, for non-Hodgkin's lymphomas the high rate in one agricultural area (Forli) was mainly due to the A sub-group in the Working Formulation (low-grade). In a heavily industrialized area (Varese), the high incidence rate was at least partly explained by a higher proportion of cases classified in the G sub-group (intermediate grade). Excesses of non-Hodgkin's lymphomas have been observed in populations exposed to phenoxy-acetic-acid herbicides, to insecticides and to organic solvents. One can hypothesize that different risk factors act on different stem cells and induce lymphoid malignancies belonging to different histologic sub-types.

Adult↗

PubMed1995

Cell proliferation patterns and p53 expression in gastric dysplasia.

Gastric dysplasia (high-grade, HGD, and low-grade, LGD) and normal mucosa were tested for anti-p53, anti-Ki-67 and anti-PCNA monoclonal antibodies on paraffin sections, and for relative AgNOR area and number on semithin Epon-Araldite sections. The proliferative compartment in normal mucosa was restricted to the middle layer corresponding to the neck-isthmus region. In LGD and HGD there was an expansion of this compartment to the lower and upper layers of mucosa, and in HGD in particular to the upper layer. p53 was always negative in LGD as well as in normal mucosa, while it was positive in 34 out of 51 cases of HGD. The most discriminant variables between LGD and HGD were relative AgNOR area and the percentages of MIB-1, p53 and PCNA. In p53-positive HGD the highest percentages of PCNA and MIB-1 were in the middle and upper layers (PCNA) or the upper layer (MIB-1), while in p53-negative HGD cases cell proliferation was maximal in the middle layer, although also present in the upper layer. The majority of cases of LGD did not demonstrate cell proliferation in the upper layer, but 5 cases behaved similarly to the p53-negative HGD cases. No significant correlations were found among percentages of MIB-1 and of PCNA and relative AgNOR area and number.

Adenocarcinoma↗

PubMed1995

Primary gastric lymphomas (MALTomas): a nuclear image analysis comparison with lymph node monocytoid B-cells and marginal zones of spleen and Peyer's patches.

Centrocyte-like cells of marginal zones of follicles of gastrointestinal lymphoid tissue, which have their analogous in marginal zone of splenic white pulp and in lymph node monocytoid B-lymphocytes, are thought to be the normal counterpart of lymphomas of MALT (MALTomas). However, the cell population of MALTomas is often polymorphic and also contains cells morphologically different from centrocytes. Since conventional morphologic analysis may not be accurate enough and the phenotype may change in different stages of B-cell lineage, the marginal zone of Peyer's patches (PMZ) and splenic white pulp (SMZ), the lymph node monocytoid B-lymphocytes (ML), 3 nodal monocytoid B-cell lymphomas (L) and 16 gastric MALTomas (M) were studied by means of automated nuclear image analysis for area, irregularity, and chromatin texture assessment. Immunophenotyping on paraffin sections and polymerase chain reaction (PCR) for detecting monoclonality and t(14-18) chromosome breakpoints at DNA levels, on paraffin section extractions, were also done. In 14 MALTomas, clonal Ig heavy chain rearrangement was detected and in none of these were found t(14-18) chromosome breakpoints. The nuclei of the control group (PMZ, SMZ and ML) showed the same morphologic characteristics, ie. size, irregularity, chromatin texture. MALTomas and nodal lymphomas were distributed into 3 clusters: (1) with larger nuclei, light chromatin (euchromatin-richer) (5 MALTomas, 2 nodal lymphomas together with the control group); (2) nuclei with the same area size, but darker (eterochromatin-richer) (6 MALTomas and 1 nodal lymphoma); (3) with smaller and darker nuclei (5 MALTomas). Chromatin textural differences were maintained in the same nuclear size class in the 3 clusters. Only a few MALTomas had nuclear features not significantly different from controls, inter-case and intra-case variability being evident.

B-Lymphocytes↗

PubMed1994

Early gastric cancer: report on 142 patients observed over 13 years.

Between 1977 and 1989, 958 patients were admitted for gastric carcinoma to the Second Department of Surgery, University of Siena, Italy. Of these, 142 (15%) had early gastric cancer. The diagnosis of this form of cancer has increased from 7% in 1977 to 22% in 1989. Following a detailed analysis of the clinical data and diagnostic techniques, it can be concluded that endoscopy is a far better method for diagnosis than x-ray. The data presented in the present paper strongly support this conclusion. Tumors were classified according to the Japanese Research Society Committee on Histological Classification of Gastric Cancer. The five-year survival rate which we have obtained is 89%, slightly lower than that of Japanese authors, but higher than that reported by other western authors. Lesions confined to the mucosa were observed in 75 patients (52.8%) while those involving the submucosa were observed in 67 patients (47.2%), with survival rates of 94 and 85%, respectively. Lymph node involvement was present in 14 cases (9.8%), with primary lymph nodes (N1) in 11 cases (7.7%) and secondary lymph nodes (N2) in three (2.1%). The five-year survival rates, with respect to lymph node involvement, was 57% in the presence of lymph node metastases and 93% in their absence (P < 0.001). The lesions were frequently found to be localized in the lower third of the stomach (106 cases, 74.6%). Patients with such lesions had a survival rate of 93%, a significant difference from those cases with lesions localized in the middle or upper third of the stomach (P < 0.05). The surgical treatment preferred in our Institute, has been subtotal gastrectomy associated with lymphadenectomy R1 and R2, leaving total gastrectomy for lesions localized in the upper third of the stomach.

Adenocarcinoma↗

PubMed1993

Epstein-Barr virus and gastric cancer: data and unanswered questions.

Sixty-five unselected cases of gastric cancer have been analysed for EBV DNA by polymerase chain reaction, in situ hybridization and immunohistochemistry for CD21 antigen expression. Four cases were found EBV-positive by PCR, while ISH yielded positive results in 3 of these cases, demonstrating EBV in the nuclei of cancerous cells. CD21 antigen was expressed in cancerous cells in all 3 ISH-positive cases. All the EBV-positive cancers of the present series were poorly to moderately differentiated adenocarcinomas with prominent lymphoid infiltration. These results are discussed also on the basis of the literature.

Adenocarcinoma↗

PubMed1992

A case-control study of cancer of the nose and paranasal sinuses and occupational exposures.

The association between nasal cancer and various occupations was investigated in a case-control study in the provinces of Verona and Vicenza (northeastern Italy) and Siena (central Italy). Cases of malignant epithelial neoplasm of the nasal cavities and paranasal sinuses diagnosed in the years 1982-1987 in the hospitals of Verona, Legnago, Bussolengo, Vicenza, and Siena comprised the study. Controls were patients admitted to the same hospitals as the cases, with any diagnosis except chronic rhino-sinusal disease and nasal bleeding. Age, gender, residency, and date of admission were taken into account by matching. Cases and controls, or their next of kin, were interviewed or required to fill in a mailed questionnaire; the overall response rate was 70%. Altogether, 78 cases and 254 controls provided information on occupational history. Significantly increased risks were associated (in males) with work in the wood industry (odds ratio [O.R.]: 5.8; 90% confidence interval [C.I.]: (2.2-16) and in the leather industry (6.8; 1.9-25). Textile workers, furnacemen, construction workers, and workers with possible exposure to organic dusts showed increased risks even if statistical significance was not reached.

Adenocarcinoma↗

PubMed1992

A case-control study of cancers of the gastric cardia in Italy.

In a case-control study of gastric cancer (GC) in high-risk and low-risk areas in Italy, 923 GCs were reviewed by one pathologist and classified according to anatomic site. There were 68 (7.4%) cancers occurring in the gastric cardia. Compared to other GCs, cardia cancer tended to occur more often in males (sex ratio 2.8 vs 1.7) and as intestinal or unclassified histologic types. Nutritional factors for cardia tumours resembled those of other GCs, showing inverse associations with the consumption of raw vegetables, citrus and other fresh fruit, and ascorbic acid, and positive associations with the intake of traditional soups and meat, protein and cholesterol, and preference for salty foods. Cigarette smoking and wine consumption were unrelated to cardia cancer risk, and there was only a weak association with total alcohol intake. Cardia tumours showed a greater familial occurrence of GC than did other sites, with a 7-fold increase in risk for those reporting two first-degree relatives with GC. The authors discuss these findings in view of the rising incidence of adenocarcinomas of the cardia and lower oesophagus that has been reported in some western countries.

Adult↗

PubMed1991

N-nitrosoproline excretion in the presence and absence of gastric disease.

N-nitrosoproline (NPRO) excretion, an indicator of endogenous nitrosation, was measured in a group of hospital inpatients who were identified by endoscopy and gastric biopsy as either having gastric lesions or having healthy stomachs. NPRO was assayed in background 24-hour urine samples and samples collected after loading doses of nitrate and L-proline. The presence of gastric lesions was associated with altered gastric pH and concomitant changes in gastric juice nitrate and nitrite concentration. Gastric juice pH increased with increasing severity of gastric disease (P = 0.031) and patients with normal stomachs had a lower gastric pH than those with chronic atrophic gastritis (CAG) (3.0 vs. 6.5, P = 0.017). The changes in gastric juice nitrate concentration were in the reverse direction (P = 0.002 for trend) with normal patients having higher mean levels than CAG patients (12.7 vs. 5.5 micrograms/ml, P less than 0.0001). Nitrite concentration increased with severity of gastric disease but the results were not significant (normal, 82.9 vs. CAG, 223.4 ng/ml, P = 0.069). No association was found between the presence of gastric lesions and increased urinary NPRO excretion. Mutagenic activity was not detected in any of the gastric juice samples.

Adult↗

PubMed1990

Topography-related expression of individual cytokeratins in normal and pathological (non-neoplastic and neoplastic) human oral mucosa.

Recently, regional changes of cytokeratin patterns in human normal non-keratinized or keratinized oral mucosa have been demonstrated and the expression of individual cytokeratin polypeptides in lesions of oral mucosa has been compared with that of normal tissues. In particular, the presence of cytokeratin 19 in the suprabasal cell layers of oral epithelia has been shown to be strongly correlated with premalignancy. In the present study, we describe the results of an immunohistochemical investigation performed using a monoclonal antibody specific for cytokeratin 1 on normal oral mucosa and benign or malignant oral lesions. We show the different distribution of this polypeptide in non-neoplastic lesions from different sites of oral mucosa and describe the presence of cytokeratin 19. Our results are in agreement with the data obtained previously. In the malignant cases we demonstrate that the distribution of the two cytokeratins is characterized by complementary patterns.

Carcinoma, Squamous Cell↗

PubMed1989

The nuclei in cutaneous malignant melanoma, stage I, are smaller in survivors than in non-survivors.

Cutaneous melanoma, stage I, from 35 survivors at 5 year follow-up and 16 non-survivors were studied. Mean nuclear area in the superficial layer was significantly larger than in the deep layer both in survivors and non-survivors, but the ratio between nuclear area in superficial and deep layers (so-called maturation index) did not differ between survivors and non-survivors. In comparison with the survivors, the mean nuclear area of non-survivors was significantly larger both in the superficial (51.1 microns2 vs 43.7 microns2, p less than 0.01) and deep (42.9 microns2 vs 36.4 microns2, p less than 0.05) layer. This points to a general increase in nuclear areas in metastasizing tumors. Furthermore, the coefficient of variation of nuclear area [(standard deviation/mean) x 100] was not different between survivors and non-survivors, either in the superficial or in the deep layer. Inspection of histograms of areas of 1000-2000 nuclei per case in 20 random cases (10 survivors and 10 non-survivors) showed a homogeneous increase in nuclear area in non-survivors. None of the histograms revealed a cell clone with especially large nuclei. These data show that the increased mean nuclear area in non-survivors is due to a homogeneous increase of all nuclei throughout the tumor and not to a special cell clone with large nuclei within nuclei of otherwise normal size. The difference in mean nuclear area in superficial and deep layers indicates that careful selection of nuclei in either of these layers is essential to obtain reproducible and comparable results with interactive morphometry.

Cell Nucleus↗