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G Bertoni

Publications and source records attributed to G Bertoni.

At least 19 recordsLinked 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

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

Cloning and transposon vectors derived from satellite bacteriophage P4 for genetic manipulation of Pseudomonas and other gram-negative bacteria.

We developed transposon and cloning shuttle vectors for genetic manipulation of Pseudomonas and other gram-negative bacteria, exploiting the unique properties and the broad host range of the satellite bacteriophage P4. P4::Tn5 AP-1 and P4::Tn5 AP-2 are suicide transposon vectors which have been used for efficient Tn5 mutagenesis in Pseudomonas putida. pKGB2 is a phasmid vector with a cloning capacity of about 7.5 kb; useful unique cloning sites are SacI and SacII in the streptomycin resistance determinant and PvuI and XhoI in the kanamycin resistance determinant. pKGB4 is a cosmid derived from pKGB2 and carries the additional cloning site SmaI in the kanamycin resistance determinant; its cloning capacity is about 18 kb. These vectors and their recombined derivatives were transferred from Escherichia coli to P. putida by transduction and may be used for other bacterial species susceptible to P4 infection.

Coliphages

Randomized placebo-controlled trial of oral liquid simethicone prior to upper gastrointestinal endoscopy.

It has been suggested that pre-procedural oral simethicone improves visibility in upper GI tract endoscopy. We examined three-hundred-thirty patients referred for upper endoscopy who were randomized and were required to swallow a placebo solution or one of three liquid simethicone solutions 15 min prior to the examination. These solutions contained 65 mg, 65 mg and 195 mg of drug dissolved in 90 ml, 30 ml and 90 ml of water, respectively. Patients treated with both dosages of simethicone revealed significantly less foam and bubbles in both the stomach and the duodenum compared to placebo. Only the 90 ml volume adequately cleared both locations. The reduction of examination time could be found both in patients with an intact stomach and in patients with or without gastric bile reflux, but was most striking in patients with previous gastric resection (examination time being reduced by almost 50% and the need of adjunctive lavage being reduced about 20 fold compared to placebo). In conclusion, pre-procedural oral simethicone should be routinely considered in patients with previous gastric resection. The utility of the drug is less evident in patients with normal gastric anatomy.

Double-Blind Method

Inhibition of Epstein-Barr virus production in P3HR-1 cells by Epstein-Barr virus-seropositive human serum.

The effect of human serum with or without Epstein-Barr virus (EBV) antibodies was characterized on virus production in P3HR-1 cells. Cell culturing with EBV-seropositive sera reduced both production of infectious virus and amounts of virion DNA in the supernatants. EBV DNA was also reduced in the cells. Such reductions in cell-associated EBV DNA depended upon the concentration of seropositive serum and incubation time. Decreased frequencies of productive EBV DNA-replicating cells were observed in cell populations which had reduced levels of cell-associated EBV DNA. The inhibitory effect of seropositive serum was reversed upon switching the cells to medium with seronegative serum. In serial sera of an acute infectious mononucleosis patient the EBV DNA-reducing activity arose in parallel to antibodies against EBV membrane antigen and nuclear antigen. Possible mechanisms were discussed for antibody-mediated inhibition of EBV production.

Antibodies, Viral

Genetic analysis of chromosomal operons involved in degradation of aromatic hydrocarbons in Pseudomonas putida TMB.

The catabolic pathway for the degradation of aromatic hydrocarbons encoded by Pseudomonas putida TMB differs from the TOL plasmid-encoded pathway as far as regulation of the upper pathway is concerned. We found, by analyzing Tn5-induced mutants and by Southern blot hybridization with appropriate probes derived from the TOL plasmid pWW0, that the catabolic genes of strain TMB were located on the bacterial chromosome and not on the 84-kb plasmid harbored by this strain. The catabolic genes of TMB and pWW0 had sequence homology, as shown by Southern blot hybridization, but differed significantly in their restriction patterns. The analysis of the mutants suggests that a regulatory mechanism similar to that present in pWW0 coexists in TMB with a second mode of regulation which is epistatic on the former and that the chromosomal region carrying the catabolic genes is prone to rearrangements and deletions.

Chromosome Mapping

Synthetic peptides to identify antigenic determinants on Epstein-Barr virus gp350/220.

We synthesized three peptides, MA1 - Thr19-Val28(+Tyr) -, MA2 - Ser807-Ala816-, and MA3-Ser718-Glu729(+Tyr) from the sequence of Epstein-Barr virus gp350/220 and immunized rabbits with these peptides. Rabbit antisera to the peptides had antipeptide radioimmunoassay titers of 1:400 for anti-MA1, 1:200 for anti-MA2, and 1:1600 for anti-MA3. The anti-MA1 serum recognized gp350/220 in Western blotting to SDS-electrophoresed proteins from 12-O-tetradecanoylphorbol-13-acetate- and n-butyrate-treated B95-8 cells, but anti-MA2 and MA3 sera did not. None of the sera reacted with gp350/220 by membrane or cytoplasmic immunofluorescence or by immunoprecipitation of Triton X-100 solubilized proteins.

Animals

Isolation and characterization of an ipt gene from the Ti plasmid Bo542.

A 1.9 kb clone of the T-DNA region of the Agrobacterium tumefaciens Ti plasmid Bo542 which exhibited homology to the isopentenyl transferase (ipt) locus of pTiA6 was identified by low stringency DNA hybridization. Introduction of this segment of pTiBo542 DNA into cells of Nicotiana tabacum or N. glauca caused tumor formation in vivo, and allowed hormone independent growth in vitro. Furthermore, this DNA segment complemented ipt mutant strains of A. tumefaciens, restoring their ability to cause tumors on Kalanchöe leaves and tomato stems. The complete DNA sequence of this segment has been determined, revealing an open reading frame homologous to other known Agrobacterium ipt genes.

Alkyl and Aryl Transferases

Intracellular synthesis of Epstein-Barr virus membrane antigen gp350/220. Inhibitory effect of monensin on its expression.

We have defined the intracellular expression and localization of gp350/220, one of the Epstein-Barr virus (EBV) induced membrane antigens, on 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and n-butyrate-treated P3HR-1 cells. 1B6 monoclonal antibody (mAb) immunoprecipitated gp350/220 from [35S]-methionine-labeled cells, as confirmed with other mAbs (2L10, 72A1, and C1), to the same membrane antigen. The appearance of gp350/220 was observed about 14 h after TPA and n-butyrate activation and reached a maximal level at about 48 h. 1B6 mAb membrane immunofluorescence-positive and cytoplasmic fluorescence-positive cells appeared progressively in cell populations at the same frequencies. Cytoplasmic immunofluorescent staining with 1B6 mAb demonstrated a paranuclear complex which was identical to a rhodamine-labeled wheat germ agglutinin-stained pattern which has been ascribed to the Golgi apparatus. We investigated the effect of monensin on gp350/220 expression and processing. Monensin at 10(-7) M significantly inhibited membrane antigen expression in the Golgi apparatus and on the cell surface, but had a negligible effect on synthesis of viral capsid antigen, early antigen, and viral DNA. The inhibition of gp350/220 with monensin was further characterized by the immunoprecipitation of gp350/220 with anti-MA-positive human sera and mAbs. Monensin treatment resulted in the accumulation of a 165-kD molecule which was judged to be a precursor of gp350/220. These results were consistent with the view that the Golgi apparatus plays an important role as a place of synthesis, processing, and maturation of gp350/220.

Antigens, Viral

Hereditary adenomatosis of the colon and rectum: clinical features of eight families from northern Italy.

Adenomatosis coli (or familial polyposis of the large bowel) and related syndromes are relatively rare diseases characterized by an autosomal dominant mode of inheritance. In these diseases, the entire colorectal mucosa is covered by hundreds (often innumerable) polyps of various dimensions. In addition, several extracolonic abnormalities have been reported. In the present study, we describe the clinical features of eight families from northern Italy fulfilling the diagnostic criteria of adenomatosis coli. Information was available on 123 unaffected and 30 affected family members. The most relevant findings of the study can be summarized as follows. 1) Gene frequency was calculated to be between 1:7,300 and 1:19,000. Segregation ratio in affected branches was 0.57, with a gene penetrance of nearly 60% and a male:female ratio of 1.73. 2) Extracolonic manifestations were present in all families and in 15 of 30 affected patients, the most frequent being cutaneous cysts and retinal lesions. No case fulfilling the classical criteria of Gardner syndrome was observed. 3) When the diagnosis of adenomatosis followed the appearance of symptoms, colorectal cancer had usually already developed, whereas no malignant changes were observed in individuals diagnosed in the asymptomatic stage. When colectomy with ileorectal anastomosis was the treatment of choice, polyps tended to recur in the rectal stump, and long-term endoscopic follow-up was necessary. In conclusion, adenomatosis coli may account for a definite proportion of colorectal neoplasms observed in the general population. Taking into consideration the genetic base of the disease, it follows that individuals at risk should be closely monitored for several years. Moreover, clinical investigations should not be limited to the large bowel, but should be extended to the skin, upper digestive tract, fundus oculi, bones, and probably other organs.

Adenomatous Polyposis Coli

Unimpaired membrane dynamics in parathyroid cells in insulin deficient rats.

The responsiveness of parathyroid cells in insulin deficient and short-term diabetic rats was investigated by morphometric analysis. Insulin deficiency was produced by intravenous injection of D-mannoheptulose and short-term (7 days) diabetes mellitus by intraperitoneal application of streptozotocin. Parathyroid glands were stimulated for parathyroid hormone secretion by decreasing the serum calcium concentration through intravenous infusion of EGTA. Parathyroid cells of controls, insulin deficient, and short-term diabetic rats responded to reduced serum calcium by a 45% increase of the cell surface area. This increase is assumed to be the result of the membrane-bound transport of parathyroid hormone from the Golgi complex and secretory granules to the plasma membrane and subsequent exocytic release of parathyroid hormone induced by the low serum calcium concentration. Therefore, the unimpaired increase in the cell surface area of parathyroid cells in insulin deficient and short-term diabetic rats indicates that insulin does not modulate the release of parathyroid hormone. It is also considered likely that synthesis of parathyroid hormone is not suppressed in short-term diabetes but that fat metabolism is disturbed leading to accumulation of lipid vacuoles.

Animals

Inhibition of Epstein-Barr virus (EBV) release from P3HR-1 and B95-8 cell lines by monoclonal antibodies to EBV membrane antigen gp350/220.

Antibody-mediated inhibition of Epstein-Barr virus (EBV) release from the EBV-productive cell lines P3HR-1 and B95-8 was probed with two monoclonal antibodies (MAbs), 72A1 and 2L10, which immunoprecipitated the same EBV membrane antigen (MA) gp350/220 found with the 1B6 MAb with which inhibition of EBV release from P3HR-1 cells was first described. These three MAbs were not equivalent in either MA reactivities or functional effects, reflecting the variable expression of different epitopes of gp350/220. 1B6 recognized MA on P3HR-1 cells, which expressed predominately the gp220 form of MA. 1B6 did not recognize (or barely recognized) a determinant on B95-8 cells. MAbs 2L10 and 72A1 reacted as well with B95-8 cells as they did with P3HR-1 cells. MAbs 1B6 and 2L10 neutralized neither P3HR-1 nor B95-8 virus, but 72A1 neutralized both viruses. MAbs 1B6 and 72A1 inhibited P3HR-1 virus release, as measured by the assay for infectious virus and by DNA hybridization analysis of released virus, but 2L10 had no such activity. 72A1 (but not 1B6) inhibited release of EBV from B95-8 cells. These experiments pointed to the presence of three different epitopes on gp350/220, identified with the respective MAbs and having varying involvement in virus neutralization and virus release inhibition.

Antibodies, Viral