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Biomedical subjects

D Basso

Publications and source records attributed to D Basso.

At least 55 records · Page 3Linked to original sources

Transforming growth factor beta, fibrogenesis and hyperglycemia in patients with chronic pancreatitis.

UNLABELLED: It has been suggested that transforming growth factor beta (TGFb) mediates liver fibrosis, which can be monitored by the serum determination of the N-terminal peptide of type III procollagen (PIIIP) and laminin. Fibrosis is also an important phenomenon in patients with chronic pancreatitis (CP). In 23 patients with CP, 38 with liver cirrhosis (LC) and 20 healthy controls we compared the serum patterns of PIIIP, laminin and TGFb and assessed whether in CP these markers are correlated with exocrine and endocrine function. In patients with LC, PIIIP and laminin levels were significantly higher, whereas TGFb levels were significantly lower than those of controls. In CP patients, no significant variations were found for PIIIP and laminin, although levels were high in 7/23 and in 5/23 patients, respectively. TGFb levels in CP patients were higher than those in LC patients, levels being raised in 6/23 patients. In LC patients an inverse correlation was found between PIIIP and TGFb, whereas in CP patients, a direct correlation was found between TGFb and PIIIP. Moreover, in CP patients, there was also a positive correlation between TGFb and fasting serum glucose levels, while laminin was correlated with PABA test results. IN CONCLUSION: serum biochemical markers of liver fibrosis can be considered of limited value in assessing pancreatic fibrosis; in liver cirrhosis there may be a negative feed-back regulation between TGFb production and the fibrogenetic process; and in chronic pancreatitis TGFb appears to favor fibrosis on the one hand and the development of hyperglycemia on the other.

Adult↗

Measurement of specific immunoglobulin E: intermethod comparison and standardization.

Recently introduced "second-generation" techniques for specific IgE measurement have produced some analytical improvement, offering better clinical sensitivity than previous techniques. The aims of our study were to compare the analytical and clinical performances of four second-generation techniques for allergen-specific IgE measurement in serum and to ascertain whether the new system for reporting quantitative results contributes to greater clinical agreement between findings using the techniques considered. Allergen-specific IgE was measured using the CAP System, CARLA, ENEA, and AlaSTAT, and the findings were compared. A significant disagreement was found between CAP and ENEA for all allergens and between CAP and CARLA for D1 and G5. However, the clinical discrepancies were reduced by selecting method-specific thresholds using ROC analysis. Second-generation techniques enable us to obtain better standardization of results; however, the identification of a specific threshold appears to be a prerequisite for the appropriate clinical interpretation of the test findings.

Adolescent↗

N-terminal peptide of type III procollagen: a possible predictor of colorectal carcinoma recurrence.

BACKGROUND: The first step of colorectal carcinoma spread depends on the ability of the tumor cells to degrade and invade the extracellular matrix (ECM). The objectives of the current study were to evaluate the serum pattern of laminin, C-terminal peptide of Type I (PIP), and N-terminal peptide of Type III (PIIIP) procollagens, markers of ECM synthesis, in the follow-up of patients after resection for colorectal carcinoma and to evaluate their role in predicting local recurrence or metastases. METHODS: A total of 32 patients who had undergone resection for colorectal carcinoma were followed for a median period of 24 months (range, 6-36 months). Every 3 months, laminin, PIP, and PIIIP were measured in the sera together with the tumor markers carcinoembryonic antigen (CEA), CA 19-9, and tissue plasminogen activator (TPA). Twenty-one patients (Group 1) had no signs of recurrence, whereas the remaining 11 (Group 2) developed hepatic (n = 7) or pulmonary (n = 4) metastases. RESULTS: No variations were observed in either group for laminin, CEA, CA 19-9, or TPA, whereas significant increases in PIP and PIIIP were observed in both groups 3 months after surgery. The increase in PIP and PIIIP at the 3-month follow-up was significantly greater in Group 1 than in Group 2. The difference between values at 3 months and basal values enabled a discrimination between Group 1 and Group 2, with a sensitivity of 36% and 91% and a specificity of 71% and 71% for PIP and PIIIP, respectively. CONCLUSIONS: The authors believe PIIIP is useful as an early prognostic indicator of recurrence in the follow-up of patients who have undergone radical resection for colorectal carcinoma.

Adult↗

An unidentified pancreatic cancer cell product alters some intracellular pathways of glucose metabolism in isolated rat hepatocytes.

In this study we assessed whether conditioned media from a human pancreatic cancer cell line (MIA PaCa 2) can interfere with some intracellular pathways involved in glucose metabolism in isolated rat hepatocytes. The hepatocytes, isolated from Male Wistar rats, were incubated with MIA PaCa 2-conditioned or nonconditioned media. Conditioned and nonconditioned hepatocytes were run for 120 min in the presence or absence of insulin (100 mM) and were sampled at fixed time intervals. Supernatant glucose levels decreased to a similar extent over time in both conditioned and nonconditioned hepatocytes, while lactate levels significantly increased in nonconditioned hepatocytes with respect to conditioned hepatocytes. A pyruvate kinase activity increase was observed only in nonconditioned hepatocytes and was biphasic in nature, since this increased activity was detected both after a few and after 30 min following insulin stimulation. The cyclic AMP level increase was significantly higher in conditioned than in nonconditioned hepatocytes. It appears that MIA PaCa 2 cells produce a factor(s) that may interfere with one of the insulin-mediated intracellular pathways of glucose metabolism, namely, glycolysis. This detrimental effect on glycolysis is supported by the blunted rise in lactate concentration in the medium after the glucose challenge. This substance(s) probably transfers its signal inside the target cells, activating the adenylate cyclase pathway. These results support the hypothesis that pancreatic cancer is the cause rather than the consequence of diabetes mellitus.

Animals↗

Helicobacter pylori genotypes influence serum pepsinogen C levels.

BACKGROUND: Infection from Helicobacter pylori significantly influences pepsinogen A (PGA) and C (PGC) levels in serum. Increased PGA and PGC serum levels are observed in H. pylori positive patients, while a significant decrease is observed after eradication. Little is known about the relative role of H. pylori cytotoxic strains in this phenomenon. The aim of our study was to assess the influence of cagA genotype on circulating levels of PGA and PGC. MATERIALS AND METHODS: We studied 81 consecutive H. pylori positive patients, 64 H. pylori negative patients and 18 healthy controls. H. pylori was evaluated histologically in two antral and two body biopsies (Giemsa and/or Warthin Starry staining). Extracted DNA was then submitted for PCR amplification of both the urease A and cagA genes. A serum obtained from each patient before endoscopy was used for specific radioimmunoassay measurement of PGA and PGC. RESULTS: The urease A gene was found in all H. pylori positive patients, the cagA gene was detected in 55 H. pylori positive patients and in none of the H. pylori negative patients. PGA and PGC levels were significantly higher in H. pylori positive than in H. pylori negative patients. A significant association was found between cagA and raised serum PGC levels in patients with antral gastritis but not in patients with peptic ulcer. Serum PGA levels were not affected by cagA. CONCLUSIONS: Our results indicate that cagA positivity may influence the circulating PGC levels, probably because it causes a higher grade of mucosal inflammation.

Adult↗

Serum tumor markers in colorectal cancer staging, grading, and follow-up.

Early diagnosis of colorectal cancer, a frequent neoplasia in industrialized countries, permits curative surgery. In this study we assessed the clinical role of serum tumor markers determination in diagnosing, staging, and grading colorectal cancer; the role of carcinoembryonic antigen (CEA), CA 19-9, tissue polypeptide antigen (TPA) and CA 72-4 in colorectal cancer follow-up was also assessed. In 114 patients with colorectal cancer, the oncofetal antigen CEA was compared with the membrane-associated glycoproteins CA 19-9, CA 242, and CA 72-4 and with the cytokeratins TPA, tissue polypeptide-specific antigen (TPS) and tissue polypeptide monoclonal antigen (TPM). Overall, the most sensitive indices were TPA and TPS (67% and 70%, respectively). Tumor stage influenced the levels of CEA, CA 19-9, and TPA, but not those of TPS, while tumor grade influenced CEA and TPS, but not CA 72-4, TPA, and TPM. TPA was the most sensitive index in identifying early or well-differentiated colorectal cancers. The sensitivity was enhanced when this marker was determined in combination with CEA, in diagnosing both advanced and early colorectal tumors. Seventy-seven patients were followed up after therapy for at least 18 months. CEA was the most sensitive index of recurrence (58%); however, this sensitivity is too low to consider tumor markers useful in colorectal cancer follow-up.

Adult↗

Serum pepsinogen C: a useful marker of Helicobacter pylori eradication?

Medical treatment for Helicobacter pylori (Hp) infection is now recommended in several types of gastroduodenal disease, and its success is usually monitored by hystology. The end-points of our work were to identify the most suitable serum index of Hp eradication among pepsinogen A (PGA), pepsinogen C (PGC), PGA/PGC ratio, gastrin, and IgG anti-Hp (IGG). We studied a total of 289 Hp positive (Giemsa staining) patients, who were treated with 40 mg/day omeprazole (140 cases) or with 480 mg/day bismuth subsalicylate (149 cases) for 4 weeks. All the patients also received 1 g/day metronidazole + 2 g/day amoxycillin for the first 2 weeks of treatment. Two months after the end of therapy, the patient underwent a second endoscopy and Hp histological assessment: the infection was eradicated in 192 and still present in the remaining 97 subjects. Gastrin, PGA, PGC, and IGG were measured before and after therapy. All indices significantly decreased after therapy in eradicated patients, while PGA and gastrin significantly decreased after therapy in both eradicated and noneradicated patients, although in the latter group the variations were less pronounced. We calculated the per cent decrease of the studied indices. PGC, with a decrease of more than 25%, was found to be the most accurate biochemical index. Variation in PGC levels before and after treatment were correlated with corresponding variations in Hp bacterial load. In conclusion, between the different biochemical parameters evaluated, PGC showed the highest clinical efficiency.

Adult↗

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↗

Cytokines may influence tumor growth and spread. An in vitro study in two human cancer cell lines.

Tumor spread may be favored by a reduced production and/or an enhanced degradation of extracellular matrix components (collagen, fibronectin, laminin). Most tumor cell behavior, from growth to spread, may be regulated by cytokines, the exact roles of which, however, are not yet fully understood. We here evaluate the effects of some cytokines (epidermal growth factor, transforming growth factor-beta 1, interleukin-1 alpha, and interleukin-1 beta) on both cell growth and the production of the aminoterminal peptide of type III procollagen, the urokinase plasminogen activator, and the plasminogen activator inhibitor-1 in neoplastic cell lines originating in the pancreas and colon. Cells were stimulated daily with the above cytokines and the aminoterminal peptide of type III procollagen, urokinase plasminogen activator, and plasminogen activator inhibitor-1 were measured in the conditioned media. Epidermal growth factor stimulated cell growth of both cell lines. Transforming growth factor-beta 1 counteracted cell proliferation and stimulated type III procollagen and plasminogen activator inhibitor-1 production only in the colon cancer cell line. Interleukin-1 alpha slightly stimulated cell growth, but inhibited plasminogen activator inhibitor-1 production in both cell lines; interleukin-1 beta did not affect cell growth, but stimulated plasminogen activator inhibitor-1 production by the colon cancer cell line. Our findings suggest that transforming growth factor-beta 1 and interleukin-1 beta may have an antidiffusive effect. These results confirm that cytokine-producing cells have a potential role in stimulating or counteracting tumor growth and spread and also confirm the pivotal role of host-tumor interactions in determining the outcome of a particular neoplasia.

Cell Division↗

Gastric juice polymerase chain reaction: an alternative to histology in the diagnosis of Helicobacter pylori infection.

BACKGROUND: Infection from Helicobacter pylori plays a role in several gastroduodenal diseases. The recent availability of molecular techniques, particularly the polymerase chain reaction (PCR), allows us to detect small amounts of this bacterium. The aims of this study were to compare PCR and histological findings and to ascertain the clinical usefulness of H. pylori PCR identification in different biological samples. MATERIALS AND METHODS: We studied 94 consecutive patients. Saliva, gastric juice, and four antral and four body biopsies were obtained from each patient. H. pylori was evaluated histologically in two antral and two body biopsies (Giemsa or Warthin-Starry stain). After extraction, DNA was submitted for PCR amplification using the two primers HPU1 and HPU2, which amplified a 411-bp product from the urease gene A. RESULTS: Forty-nine patients were H. pylori-positive at histological workup. The sensitivity of PCR was 92% for gastric juice, 73% for antral biopsies, 61% for body biopsies, and 13% for saliva. Of the 45 H. pylori-negative patients at histological assessment, 7 (16%) had positive findings on PCR, mainly when gastric juice was examined. CONCLUSIONS: These results indicate that PCR is as sensitive as histological assessment. We suggest that PCR H. pylori detection in gastric juice is a sensitive method for diagnosing this infection.

Adult↗

Helicobacter pylori serology in patients with chronic gastritis.

OBJECTIVES: Helicobacter pylori (Hp) infection is known to cause several gastroduodenal diseases. In patients with non-ulcer dyspepsia, we assessed the link between Hp infection and gastric mucosal inflammation, as well as the influence of Hp and inflammation on the serum levels of anti-Hp antibodies (IgG), pepsinogen A (PGA), pepsinogen C (PGC), and gastrin. METHODS: Entering the study were 221 patients with non-ulcer dyspepsia, all of whom underwent upper gastrointestinal endoscopy. RESULTS: Of the 221 patients investigated, 135 (61%) were Hp positive. The higher the bacterial load, the worse the associated gastritis, the gastric antrum and body being considered. All of the serological indices studied were found to be influenced by gastritis. Serum IgG satisfactorily discriminated between Hp-positive and Hp-negative subjects, with a sensitivity of 84% and a specificity of 86%. PGC, PGA, and gastrin were less accurate. Only PGC only found to be correlated with Hp load. The product of IgG and PGC improved the diagnostic accuracy of IgG alone. CONCLUSIONS: Hp infection, frequently found in patients with non-ulcer dyspepsia, is associated with gastric mucosal inflammation; of the indices studied, serum IgG and PGC most accurately indicated Hp infection, and their product may be proposed as an aid in diagnosing Hp infection in dyspeptic patients.

Adult↗

[The role of the laboratory in the diagnosis and monitoring of Helicobacter pylori infection].

The diagnosis of Helicobacter pylori infection represents a fundamental step for a correct clinical approach to the patient with gastritis, peptic ulcer or gastric adenocarcinoma or lymphoma. Upper gastrointestinal endoscopy has first to be made in order to obtain gastric juice and mucosal biopsies, where Hp can be found. Two different procedures are recommended to diagnose Hp infection (e.g. urease test and histology or culture). The identification of specific DNA sequences with the polymerase chain reaction represents a sensitive and specific method to diagnose Hp infection. Serum anti Hp antibodies, pepsinogen A and C determination is recommended at diagnosis and during the follow-up to assess the success of therapy.

Chronic Disease↗

Receiver-operating characteristic (ROC) curves: a fundamental tool for improving the clinical usefulness of in vitro IgE tests.

In order to establish the most efficient thresholds for serum allergen-specific IgE measured by the Pharmacia CAP System, a "second-generation" in vitro method, we evaluated results from 89 subjects with suspected inhalant allergies, using receiver-operating characteristic (ROC) curve analysis. Sera samples were analyzed by the Pharmacia CAP System for specific IgE, the choice of allergens to be tested being based upon the symptoms and clinical history of each patient. Results were analyzed by ROC analysis for the five most representative allergens, cat dander (e1), Dermatophagoides pteronyssinus (d1), Lolium perenne (g5), wall pellitory (W19), and wormwood (w5). The areas under the ROC curves were found to be satisfactory, ranging from 0.931 (e1) to 0.974 (g5) when we excluded w5, which had a significantly smaller area (0.81). To establish the most efficient threshold for each allergen, we calculated the clinical sensitivity, specificity, efficiency, and negative and positive predictive values. The thresholds giving a higher diagnostic efficiency were as follows: 0.40 kUa/l for d1, 0.55 kUa/l for g5, 0.50 for e1, 0.65 kUa/l for w19, and 1.00 kUa/l for w5. It is concluded that quantitative reporting of specific IgE measurement has numerous advantages, but the choice of the positive threshold seems to be a prerequisite for obtaining the optimal clinical efficiency. It is also suggested that a specific threshold should be adopted for each allergen.

Adolescent↗

Influence of Helicobacter pylori on tryptase and cathepsin D in peptic ulcer.

We here ascertain whether tryptase (a serine endoprotease released by mast cells) and cathepsin D (CD, a lysosomal hydrolase that seems able to derange the extracellular matrix) play a part in peptic ulcer disease and whether they are linked to Helicobacter pylori (Hp) infection. We studied 13 controls, 25 patients with gastric ulcer, 47 with duodenal ulcer, and 11 with duodenitis. Tryptase and CD were measured in mucosal biopsies (body and antrum of the stomach and duodenum) using IRMA methods. Hp infection was histologically evaluated (Giemsa). Tryptase and CD levels were higher (25%) in patients with active peptic ulcer, whether gastric or duodenal. In Hp-positive patients the CD mucosal content was higher while tryptase mucosal levels were lower than in Hp-negative patients. Tryptase was correlated with gastrin content. CD seems to be mainly related to the phlogistic reaction of the mucosa to Hp infection; tryptase may reflect an indirect link between Hp infection, gastrin release, and the function of mast cells.

Adult↗

Gastrin stimulates gastric mast cells in rabbits.

In a previous study we demonstrated that in human gastric mucosa tryptase was localized only in mast cells and that its levels were correlated with serum gastrin, suggesting a link between gastrin action and mucosal mast cell function. The aim of the present study was to discover whether pentagastrin injection could stimulate gastric mucosal mast cells in rabbits. Ten female rabbits (group S) were injected s.c. with pentagastrin (10 mu g/kg); another group of ten animals (group C) was injected s.c. with an equal volume of saline solution. One hour after the injection the rabbits were sacrificed and their stomachs removed. Antrum (A), corpus (C) and fundus (F) mucosal homogenates were assayed for total protein, tryptase, pepsinogen A (PGA), histamine and gastrin. Histamine tissue levels were significantly lower in group S than in group C in the antrum (Mann-Whitney test: U = 82, P < 0.01) and in the corpus (U = 83, P < 0.005). Tryptase levels were significantly higher in group S than in group C in all gastric areas (antrum: U = 95, P < 0.001; corpus: U = 85, P < 0.005 and fundus: U = 75, P < 0.05). Total protein, PGA and gastrin did not vary significantly between groups. In group C, no significant correlations were found among the five parameters. In group S, corpus tryptase was correlated with fundus tryptase (Spearman's r = 0.831, P < 0.01). The same relationship was observed for histamine (r = 0.672, P < 0.05). In group S, antrum gastrin was inversely correlated with antrum tryptase (r = -0.903, P < 0.001), and with corpus PGA (r = -0.806, P < 0.05). This study demonstrates that bolus pentagastrin administration stimulates gastric mucosal mast cells in the rabbit.

Animals↗