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Biomedical subjects

G Bertoni

Publications and source records attributed to G Bertoni.

At least 73 records · Page 4Linked to original sources

First observation of microadenomas in the ileal mucosa of patients with familial adenomatous polyposis and colectomies.

BACKGROUND & AIMS: Little data are available on the type and prevalence of mucosal changes involved in the development of ileal adenomas in patients with familial adenomatous polyposis who have undergone colectomy. However, colonic metaplasia of the ileal epithelium is thought to be an important step in the development of such adenomas. METHODS: Retrograde endoscopy and biopsy of the distal ileum were performed in 17 affected patients who underwent total colectomy or proctocolectomy 3-184.1 months (mean, 80.3 +/- 13.9 months) before the study. RESULTS: Macroscopic ileal polyps were identified in 14 (82.4%) patients. All polyps were sessile and 1-5 mm in size. Histological analysis showed adenomas in 9 (52.9%) patients and lymphoid hyperplasia or inflammation in the others. In 1 patient, an area of colonic-type metaplasia of the ileal mucosa was found close to an adenoma. However, in 5 (29.4%) patients, random biopsy specimens of the normal-appearing mucosa showed foci of abnormal crypts in the absence of metaplasia, with histological appearance similar to the findings described in dysplastic aberrant crypt foci of the colon. Such lesions, previously observed only in colorectal mucosa and referred to as microadenomas or oligocryptal adenomas, are considered putative preneoplastic abnormalities. CONCLUSIONS: Although the hypothesized sequence normal ileal mucosa leading to colonic-type metaplasia leading to adenoma cannot be excluded, our findings support the sequence normal ileal mucosa leading to microadenoma leading to gross adenoma and possibly cancer as the main histogenetic pathway, as already suggested for the large bowel.

Adenoma↗

Antibody responses to Epstein-Barr virus, human herpesvirus 6 and human herpesvirus 7 in patients with chronic fatigue syndrome.

To test for an association between chronic fatigue syndrome (CFS) and infections with Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7), antibodies to these viruses were tested in the serum from three groups of individuals: (1) 10 CFS patients with chronic fatigue beginning with a clinical pattern of acute infectious mononucleosis [IM; true chronic IM (CIM)]; (2) 10 CFS patients whose illness did not start with acute IM (non-CIM), and (3) healthy controls. High EBV antibody titers were demonstrated in most patients. Antibodies to ZEBRA, a product of the immediate early EBV gene BZLF1, were detected in the serum of CFS patients at a higher frequency than in healthy controls. Antibody titers to HHV-6 and HHV-7 were also higher in the patients with CFS than in the controls. These results are consistent with the view that CFS patients may have reactivations of EBV, HHV-6 and HHV-7.

Adult↗

Clinical and biologic features of adenomatosis coli in Northern Italy.

BACKGROUND: Familial adenomatous polyposis (FAP) is a hereditary disease characterized by more than 100 adenomas scattered in the large bowel and by various extracolonic manifestations. We proposed a) to establish the frequency of the disorder in Northern Italy, b) to describe the most relevant clinical findings, and c) in a subgroup of 21 patients (from 8 families), to evaluate the spectrum of mutations of the APC gene. METHODS AND RESULTS: Patients with FAP diagnosed between 1961 and 1991 were referred to our Study Group from surgery and gastroenterology units of the region Emilia-Romagna. The incidence of FAP was in the order of 1 in 16,500, with about a third of patients being 'single' cases. Colorectal malignancies were present in 75.6% of symptomatic patients but absent in most (93.75%) of the asymptomatic family members ('call-up' individuals). Gastric, duodenal, and jejunal adenomas were found in 8.2%, 30.6% and 53.3% of the investigated patients, respectively. Congenital hypertrophy of the retinal pigment epithelium and occult jaw lesions were seen in 64.7% and 39.5% of FAP patients but only in 0.5% and 2.5% of a matched, by age and sex, control population. These two clinical markers had a specificity of 99% and 97%, although their sensitivity was 64% and 39%. Finally, mutations of the APC gene were detected in 6 families (16 affected individuals) of the 8 families (21 affected individuals) tested; no correlation could be found between genotype and phenotype. CONCLUSIONS: This study confirms that early diagnosis is essential for an appropriate management of FAP patients, although this aim remains elusive in single cases. High-risk individuals are ideal candidates for APC gene mutation analysis, which should be offered to all first-degree relatives of affected patients.

Adenomatous Polyposis Coli↗

Antibody reactivity to the immunodominant epitopes of the caprine arthritis-encephalitis virus gp38 transmembrane protein associates with the development of arthritis.

High titers of antibodies to caprine arthritis-encephalitis virus (CAEV) envelope (Env) glycoproteins are found in infected goats developing a progressive arthritis. In order to identify linear B epitopes of the CAEV Env, which may be involved in the immunopathology of arthritis, we constructed a lambda gt11 Env expression library. By combining library screening with sera from naturally infected Swiss goats with an enzyme immunoassay with overlapping peptides (pepscan), four group-specific epitopes could be precisely defined in the transmembrane envelope proteins: TM1 to TM4, including a conserved structure (TM3) that corresponds to the immunodominant epitope of human immunodeficiency virus type 1 and other lentiviruses. A panel of 190 CAEV naturally infected goat serum samples, obtained from animals with defined clinical status, was tested for reactivity to synthetic peptides corresponding to the TM epitopes in an enzyme-linked immunosorbent assay. Antibody reactivity to two epitopes was highly associated (TM3, P = 0.002, and TM4, P < 0.001) with the presence of clinically detectable arthritis. Such an association is absent for anti-Gag antibody. Antibodies to the immunodominant structures of the TM glycoprotein could thus have an important role in the immunopathogenic process leading to disease.

Amino Acid Sequence↗

Oral isosorbide-5-mononitrate reduces the rebleeding rate during the course of injection sclerotherapy for esophageal varices.

A double-blind, multicenter trial was carried out to assess the effectiveness of isosorbide-5-mononitrate in preventing recurrent variceal hemorrhage during the course of endoscopic sclerotherapy. Seventy-six patients with their first bleeding episode from esophageal varices were randomly allocated, after initial control of hemorrhage, to groups receiving either 50 mg/day oral isosorbide-5-mononitrate retard (37 patients) or an identical placebo (39 patients) until variceal eradication. Sclerotherapy was performed at weekly intervals, and varices were intra- and para-variceally injected with 1% polidocanol until eradication. If rebleeding occurred, additional sclerotherapy was performed. Four (10.8%) patients rebled in the isosorbide group, compared with 15 (38.4%) in the placebo group (p = 0.01). The total number of rebleeding episodes was also significantly lower in the isosorbide group (5 versus 19, p = 0.043), whereas comparison between major versus minor rebleedings was not significant. The median transfusion requirement per bleeding episode was not significantly different in the two groups, although the cumulative number of blood units transfused was over threefold greater (22 versus 70) in the placebo group. Two (5.4%) deaths occurred among isosorbide-treated patients and nine (17.9%) among placebo patients (NS). The number of sclerotherapy sessions and the time required to obtain variceal eradication were also comparable in the two groups. Finally, the nitrovasodilator was well tolerated, requiring withdrawal for severe headache in only one patient. In conclusion, isosorbide-5-mononitrate reduces the rebleeding rate and the number of rebleeding episodes before variceal eradication in patients treated with sclerotherapy.

Administration, Oral↗

[Variations in the antibiotic sensitivity of bacterial strains after contact with the metals used for the construction of prosthetic implants].

The antibiotic sensitivity of 19 Gram-positive bacterial strains (11 Staphylococcus aureus and 8 Staphylococcus epidermidis) and 16 Gram-negative strains (8 Escherichia coli and 8 Proteus species) was evaluated after contact with stainless steel and with some metals compounding the alloys used for prosthetic devices. The hypothesis was that the resistance to antibiotic therapy of infections associated with prosthetic implants is also due to a modification in the sensitivity of microorganisms. The results, compared to those obtained from control tests, showed only slight variations in the antibiotic sensitivity of the strains put in contact with the metals. In Gram-positive strains, after contact with metals, the increase in sensitivity occurred more frequently than the reduction. In Gram-negative strains, the decrease in sensitivity was more frequent than the increase. Proteus strains showed sensitivity variations more frequently than Escherichia coli strains. Titanium and nickel induced the highest number of variations, both in Gram-positive and Gram-negative strains.

Anti-Bacterial Agents↗

Ectopic sebaceous glands in the esophagus: report of three new cases and review of the literature.

Ectopic sebaceous glands in the esophagus are a very rare anomaly which have, until now, been described in only 14 living individuals. We describe here the macroscopic, pathological, and clinical features of three new endoscopically diagnosed cases of this benign condition. One of the three patients showed a very high number of lesions (more than 100) distributed throughout the esophagus. A review of the existing literature is presented and the possible pathogenetic mechanisms involved are discussed.

Adult↗

Improved bioassay for the detection of porcine tumor necrosis factor using a homologous cell line: PK(15).

Close similarities of various physiological parameters makes the pig one of the preferred animal models for the study of human diseases, especially those involving the cardiovascular system. Unfortunately, the use of pig models to study diseases such as viral hemorrhagic fevers and endotoxic shock syndrome have been hampered by the lack of the necessary immunological tools to measure important immunoregulatory cytokines such as tumor necrosis factor (TNF). Here we describe a TNF-bioassay which is based on the porcine kidney cell line PK(15). Compared to the widely used murine fibroblastoid cell line L929, the PK(15) cell line displays a 100-1000-fold higher sensitivity for porcine TNF-alpha, a higher sensitivity for human TNF-alpha, and a slightly lower sensitivity for murine TNF-alpha. Using a PK(15) bioassay we can detect recombinant TNF-alpha as well as cytotoxic activity in the supernatants of lipopolysaccharide (LPS)-activated porcine monocytes at high dilutions. This suggests that the sensitivity of the test should permit the detection of TNF in biological specimens such as pig serum.

Animals↗

Expression of BCL-2 protein enhances the survival of mouse fibrosarcoid cells in tumor necrosis factor-mediated cytotoxicity.

Tumor necrosis factor (TNF) kills some types of tumor cells in vitro and participates in tumor elimination in vivo. TNF has been shown to kill cells by altering their mitochondria structurally and functionally. The oncogene BCL-2 codes for a protein located in the inner membrane of mitochondria which is able to inhibit the commitment to cell death in various cell types. We have therefore investigated whether TNF-mediated killing of the cell line L929 could be modulated by expression of the protein BCL-2. We report here that L929 cells transfected with a BCL-2 expression vector have an increased survival compared to wild type cells after TNF challenge. The protective effect is greatest at moderate TNF concentrations and is still significant at concentrations that killed 100% of wild type cells. The action of BCL-2 is selective inasmuch as cells are not protected against other cytotoxic agents blocking various mitochondrial functions. We show that cells expressing BCL-2 have a higher mitochondrial membrane potential (delta psi) than wild type cells. The increase in delta psi could be linked with the enhanced survival of cells after TNF challenge. Indeed, we found that treatment of wild type L929 cells with the ionophore nigericin, which increases delta psi, protects them even at high TNF concentrations.

Animals↗

A novel early antigen associated with Epstein-Barr virus productive cycle.

A murine monoclonal antibody (mAb) 92A recognized a 48-kilodalton Epstein-Barr virus (EBV) early antigen (EA). The mAb stained nuclei of EBV-activated P3HR-1, B95-8 and Akata cells in a distinctive, microgranular immunofluorescence pattern. The 92A antigen was sensitive to methanol-fixation. Expression of the 92A antigen in those cells paralleled diffuse (EA-D) and restricted (EA-R) components of EA, and viral DNA (vDNA) replication. Phosphonoacetic acid did not inhibit expression of the 92A antigen. The colocalization of 92A antigen, EA-D, and vDNA was observed in viral replication compartments of B95-8 cells. On the other hand, in P3HR-1 virus-superinfected Raji cells the percentages of 92A antigen-positive cells were at much lower levels than were EA-D and -R positive cells. Immunofluorescence staining with 92A mAb was blocked by pretreatment with EBV-positive human sera, but not with EBV-negative sera. We conclude that 92A mAb recognizes a novel EA which may function in vDNA replication.

Animals↗

Antioxidant vitamins or lactulose for the prevention of the recurrence of colorectal adenomas. Colorectal Cancer Study Group of the University of Modena and the Health Care District 16.

Colonic adenomas represent the natural precursor lesions of most colorectal cancers. The treatment of choice is endoscopic polypectomy. However, after endoscopic removal, polyps recur in a large fraction of cases. Thus, we evaluated the effect of antioxidant vitamins or lactulose on the recurrence rate of adenomatous polyps. After polypectomy, 255 individuals were randomized into three groups. Group 1 was given vitamin A (30,000 IU/day), vitamin C (1 g/day), and vitamin E (70 mg/day); Group 2 was given lactulose (20 g/day); Group 3 received no treatment. Forty-six subjects had to be excluded because the histologic diagnosis was not consistent with adenoma. The remaining 209 individuals were included in the analysis according to the "intention to treat" criterion, though 34 did not adhere to the scheduled treatment or were lost during the follow-up. Subjects were followed at regular intervals for an average of 18 months. Polyps recurring before one year from index colonoscopy were considered missed by the endoscopist. In the 209 evaluable subjects, the percentages of recurrence of adenomas were 5.7 percent, 14.7 percent, and 35.9 percent in the vitamins, lactulose, and untreated groups, respectively. The fraction of subjects remaining free of adenomas, estimated by Kaplan-Meier survival curves, was significantly different among the three groups (log-rank chi-squared = 17.138; P < 0.001). Using Cox's regression analysis, treatment was the only variable that significantly contributed to the model (regression coefficient = 0.905; P < 0.001). In conclusion, either antioxidant vitamins or, to a lesser extent, lactulose lower the recurrence rate of adenomas of the large bowel and can be proposed as chemopreventive agents, at least in high-risk individuals.

Adenoma↗

Generalized juvenile polyposis with mixed pattern and gastric cancer.

Generalized gastrointestinal juvenile polyposis is a rare form of diffuse polyposis in which cancer infrequently develops. A clinical case is described in which gastric polyps showed a variety of histological features, including both in situ and invasive adenocarcinoma. Many mixed lesions were observed, confirming a morphological sequence already documented in colorectal tumorigenesis but still undefined in gastric tumors. The patient seems strongly predisposed to gastric cancer, presumably on a genetic basis, because he developed a malignancy in a hyperplastic juvenile polyp, usually not considered a precancerous lesion. There is no doubt that cases like this may be important for accurate genetic evaluation and biological characterization.

Adenocarcinoma↗

Cloning and expression in mammalian cells of porcine tumor necrosis factor alpha: examination of biological properties.

We have cloned a full length complementary DNA (cDNA) of the porcine tumor necrosis factor alpha (pTNF-alpha) gene and expressed it in porcine and murine cells. Total RNA obtained from lipopolysaccharide (LPS) stimulated porcine peripheral blood mononuclear cells was reverse transcribed with a specific antisense pTNF-alpha primer to generate a single stranded cDNA which was subsequently amplified by the polymerase chain reaction utilizing an additional pTNF-alpha specific sense primer. The resulting double stranded cDNA was introduced into the pBMGNeo expression vector and transfected by electroporation in porcine (PK(15)) and murine (L929) cell lines. TNF-alpha bioactivity was detected in the supernatant of the transfected cells using a standard L929 bioassay or a PK(15) bioassay. The activity was zinc inducible as expected for a gene controlled by a metallothionein promoter. The bioactivity was not lowered by an anti-mouse TNF-alpha antiserum neutralizing murine, but not human TNF-alpha and a broad immunoreactive band of 17-19 kD was detected using an anti-mouse TNF-alpha serum suitable for immunoblotting. This newly developed tool will allow us to investigate the role of TNF-alpha in pathogenesis of viral infections and gram-negative sepsis.

Animals↗

Expression and characterization of bioactive recombinant ovine TNF-alpha: some species specificity in cytotoxic response to TNF.

We have expressed and partially purified recombinant ovine tumour necrosis factor alpha (rovTNF-alpha) using a yeast Ty, virus like particle, expression system. RovTNF-alpha is at least as active as recombinant human TNF-alpha (rhTNF-alpha) in two different bio-assays performed on ovine material, whilst approximately 1000-fold more rovrTNF-alpha than rhTNF-alpha is required to induce the same level of cytotoxicity in TNF-sensitive murine cell lines L929 and WEHI 164 clone 13. When cytotoxic assays are performed on the porcine TNF sensitive cell line PK(15)-1512, rovTNF-alpha shows about 2 logs greater activity than on murine cells, whilst rhTNF-alpha is about 1 log more active. A monoclonal antibody, raised against rovTNF-alpha, has been used to demonstrate the presence of nanogram amounts of an appropriately sized glycoprotein to be native ovine TNF-alpha in supernants of LPS stimulated ovine alveolar macrophages. These samples show no detectable cytotoxicity to L929 cells, although they show activity attributable to TNF-alpha (through neutralization by a polyclonal antiserum raised to rovTNF-alpha) in an assay on ovine material. The relative lack of activity on murine cells helps to explain previous reports of inability to assay native ovine TNF-alpha using these cells, in spite of their routine use to assay TNF-alpha from several other species. The sequence features in ovine TNF-alpha which might reduce its affinity for the murine TNF type 1 receptor are discussed.

Amino Acid Sequence↗

Jejunal polyps in familial adenomatous polyposis assessed by push-type endoscopy.

Cancer of the upper gastrointestinal tract is a leading cause of death in patients with familial adenomatous polyposis who have previously undergone total colectomy. The prevalence and the degenerative risk of gastric and duodenal adenomas has been well documented, but little is known about the occurrence of jejunal polyps in these patients. We evaluated 21 (16 affected and five high-risk) subjects in nine families prospectively in order to assess the frequency of polyps in the upper jejunum. With the push-type technique, it has been possible to insert a standard gastroduodenoscope or a longer fiberscope 15-80 cm beyond the ligament of Treitz. Eight out of 16 (50%) affected patients and none of the nonaffected subjects had polyps. All lesions were adenomas, including a 4-cm tubulovillous adenoma with severe dysplasia, and were almost exclusively located in the first 20 cm of jejunum. The depth of insertion obtained with gastroduodenoscopes was significantly smaller than that obtained with longer endoscopes (pediatric colonoscope or experimental enteroscope). However, the jejunal area thought to be at the highest risk of adenoma (the proximal 20 cm) was usually investigated even with standard 105-cm long gastroduodenoscopes. This study confirms that the upper jejunum has a high prevalence of adenomas in patients affected by familial adenomatous polyposis and that proximal jejunoscopy is a worthwhile, not excessively uncomfortable procedure that should be added to the usual follow-up protocols.

Adenomatous Polyposis Coli↗

A new protector device for safe endoscopic removal of sharp gastroesophageal foreign bodies in infants.

The accidental ingestion of sharp foreign bodies into the upper-gastrointestinal tract is not uncommon in children. Endoscopic extraction of these objects poses technical difficulties, and a number of dangerous complications can occur. We present two cases of successful retrieval of large, sharp gastroesophageal foreign bodies in small children using a new, commercially available endoscopic end protector hood that prevents exposure of the esophageal and pharyngeal wall to injuries and laceration by the foreign body. This device is simple to use, versatile, and effective and advances the safe endoscopic removal of a variety of gastroesophageal foreign bodies in pediatric patients.

Child, Preschool↗

Morphometric analysis of parathyroids in hypophysectomized rats in normocalcaemic and short-term induced hypocalcaemic conditions.

The ultrastructure of parathyroid glands of hypophysectomized rats in normo- and hypocalcaemic conditions was qualitatively and quantitatively analysed. Parathyroid glands of both intact and hypophysectomized rats comprised cells of similar shape and staining intensity and of an equal number of cells in mitosis. Cell volume was not affected but the surface area of plasma membrane, RER and Golgi complex was increased in parathyroid cells after hypophysectomy. Parathyroid cells of both intact and hypophysectomized rats responded to hypocalcaemia by a drastic increase in surface area of the plasma membrane and a decrease in surface area of the Golgi complex. Since RER, Golgi complex and plasma membrane are concerned with secretion of parathyroid hormone, the data suggest that (1) the pituitary has either no effect on parathyroid cells, or a possibly stimulating effect can be compensated after hypophysectomy, or the pituitary even has a suppressive effect on parathyroid cells, and (2) the responsiveness of parathyroid cells to changes in serum calcium is unimpaired after hypophysectomy.

Animals↗