Genetic evidence that juvenile nasopharyngeal angiofibroma is an integral FAP tumour.
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Adenomatous Polyposis Coli↗
Biomedical subjects
G Aceto
Publications and source records attributed to G Aceto.
Desmopressin for the treatment of nocturnal bedwetting in patients with neural tube closure defects.
PURPOSE: We evaluated desmopressin (DDAVP) treatment in patients with neuropathic bladder secondary to neural tube closure defects (NTDs) and nocturnal incontinence. MATERIALS AND METHODS: We selected 25 patients, that is 10 males (40%) and 15 females (60%), between ages 7 and 16 years (mean 9.8) with neuropathic bladder secondary to NTDs without a ventricular-peritoneal shunt. All had a low pressure bladder and presented with daytime continence between catheterizations but had persistent nocturnal urine loss 7 nights weekly. They underwent treatment with oral DDAVP according to a certain design, namely an initial dose of 0.2 mg for 3 weeks, which was increased to 0.3 or 0.4 mg for another 3 weeks in nonresponders. The average dose was 0.2 mg. At the effective minimal dose (bedwetting decrease greater than 50%) patients continued for 6 months and then decreased by intervals of 0.05 mg every 2 weeks. In the event of recurrence treatment continued for 1 year. RESULTS: All patients responded to treatment during the nighttime hours except 1 who suspended treatment after 4 weeks. There were no adverse effects from DDAVP. CONCLUSIONS: Treating nocturnal bedwetting with DDAVP in patients with NTDs was effective and safe. Nevertheless, to our knowledge treatment duration has not yet been determined.
Adolescent↗
BRCA1 and BRCA2 mutations in breast/ovarian cancer patients from central Italy.
We report on the screening of the entire BRCA1/BRCA2 coding sequence by SSCP, PTT, and direct sequencing in 68 Italian families with recurrent breast or ovarian cancer. For each investigated proband, the probability of being carrier of a BRCA1/BRCA2 mutation was evaluated using the BRCAPRO software. We detected BRCA1/BRCA2 mutations in 8 patients (11.7%). However, if considering only patients with a carrier probability >10%, the detection rate was 36.8%, confirming the usefulness of the BRCAPRO software. One change (BRCA1 4172insT) was a novel mutation not reported in BIC database.
Adult↗
APC gene mutations and colorectal adenomatosis in familial adenomatous polyposis.
Correlations between germline APC mutation sites and colorectal pathophenotypes, as evaluated by the direct count of adenomas at colectomy, were investigated analysing colectomy specimens from 29 FAP patients carrying one mis-sense (codon 208) and 14 frame-shift or non-sense APC mutations (codons 232, 367, 437, 623, 876, 995, 1061, 1068, 1075, 1112, 1114, 1309, 1324, 1556). The mis-sense mutation at codon 208 was associated with a relatively mild colorectal pathophenotype. The mutation at codon 367, subject to alternative splicing, was associated with attenuated FAP. The mutation at codon 1309 was associated with the profuse colorectal adenomatosis. For 13 mutations, predicted to result in null alleles or truncated APC proteins, we correlated density and distribution of colorectal adenomas with the predicted functional effects of the mutation. The most severe colorectal pathophenotype was significantly associated with the truncating mutation at codon 1309, which is located downstream to the I beta-catenin binding domain but upstream II beta-catenin-binding domain. Mutations between codons 867 and 1114, which affect the I beta-catenin binding domain, as well as mutations occurring in exons 6 and 9, predicted to result in null alleles, were associated with a less severe colorectal pathophenotype. Overall, the highest number of adenomas was detected in the right colon, followed by the left colon, transverse colon sigma and rectum. However, the highest density of adenomas was observed in the left colon, followed by the right colon, sigma, transverse colon and rectum. Colorectal carcinomas, observed in only five patients, were all in the left colon.
Adenoma↗
Unbalanced germ-line expression of hMLH1 and hMSH2 alleles in hereditary nonpolyposis colorectal cancer.
We analyzed the hMLH1 and hMSH2 genes in 30 unrelated hereditary nonpolyposis colorectal cancer (HNPCC) patients using mutational and immunohistochemical analyses combined whenever possible with primer extension assays, designed to estimate hMLH1 and hMSH2 transcript expression in peripheral blood lymphocytes. Single-strand conformational polymorphism screening and PCR-direct sequencing revealed seven hMLH1 and five hMSH2 sequence variants in 14 unrelated HNPCC patients, including three definite pathogenic mutations, four amino acid substitutions of uncertain pathogenic significance, and five polymorphisms. Immunohistochemistry indicated the lack of either hMLH1 or hMSH2 protein expression in tumors from 13 patients, and the absence of both hMLH1 and hMSH2 immunostaining was observed in the tumor from one additional case. The lack of hMLH1 or hMSH2 immunostaining was associated with the presence of microsatellite instability in the corresponding tumor and was also observed in tumors from patients negative for pathogenic mutations by mutational screening. There was a marked unbalance in the allelic expression of either hMLH1 or hMSH2 transcripts in three of eight unrelated HNPCC patients that could be analyzed, although a less marked unbalance was detected in two additional patients. Tumors from patients with germ-line unbalance in hMLH1 or hMSH2 transcript expression did not express the corresponding mismatch repair protein and displayed microsatellite instability. Our results indicate that constitutional alterations in hMLH1 and hMSH2 transcript expression may represent genetic markers for HNPCC carrier status also in cases in which mutational analysis did not detect a definite pathogenic variant. This suggests that transcript deregulation may represent a relevant mode of germ-line inactivation for mismatch repair genes.
Adaptor Proteins, Signal Transducing↗
Nocturnal enuresis can be caused by absorptive hypercalciuria.
OBJECTIVE: The aim of this study was to determine whether nocturnal enuresis (NE) can be caused by absorptive hypercalciuria. MATERIALS AND METHODS: From 1981 to 1995, 406 patients with primary monosymptomatic nocturnal enuresis were studied. Up to 1989 (Group 1), urinary electrolytes and urinary creatinine were not evaluated, but since 1990 (Group 2) these tests have been performed routinely. In doing so, we noticed that in 8 patients in Group 2 and in 13 patients in Group 1 with persistent NE the urinary calcium and the urinary calcium/creatinine ratios were significantly high (p < 0.001). These patients were submitted to Pak's test and parathyroid hormone (PTH) and antidiuretic hormone (ADH) measurements. RESULTS: In all 21 patients, PTH and ADH levels were normal, while the Pak's test showed absorptive hypercalciuria. They were given an appropriate diet. After 3 months, NE had ceased completely in 4 patients (19%); bedwetting episodes diminished and calciuria levels were found to be borderline in the remaining 17. A new urodynamic evaluation showed normal patterns in 12 and detrusor instability (DI) in 5. Patients with DI received oxybutinine: enuresis disappeared in all. The remaining 12 children with persistent NE and normal urodynamic findings and the child with DI and persistent NE empirically received DDAVP; enuresis ceased in all of them within 1 month and calciuria stabilized at normal levels. CONCLUSIONS: This study revealed that absorptive hypercalciuria can be responsible for NE and can be treated with the combination of diet and DDAVP.
Calcium↗
Transcript dosage effect in familial adenomatous polyposis: model offered by two kindreds with exon 9 APC gene mutations.
Analysis of genotype-phenotype correlations in familial adenomatous polyposis (FAP) patients demonstrated that the phenotypic heterogeneity of FAP is partly related to the mutation site. We investigated the molecular basis for the difference in severity of colorectal disease observed comparing FAP patients from two kindreds with neighbouring germline mutations in exon 9 of the APC gene. Patients from one kindred presented with a attenuated form of FAP, characterized by a low number of colorectal adenomas (up to 22). In FAP patients from this kindred, the APC gene mutation was localized at codon 367, in the portion of exon 9 that is alternately spliced. This is expected to result in the splicing-out of the mutation site in a fraction of mRNA molecules and in the residual production of wild-type transcripts from the mutant APC allele. Patients from the other kindred manifested a FAP phenotype characterized by hundreds of colorectal adenomas (320 to > 500). In these patients, the APC gene mutation abolished the donor site of exon 9a, used in both alternately spliced isoforms of the exon. The analysis of the relative levels of mutant and wild-type transcripts in unaffected colonic mucosa demonstrated that the mutant allele was not expressed. The model offered by our FAP patients with neighbouring exon 9 APC mutations supports the view that in addition to the mutation site, the type of mutation and transcript dosage effects contribute to the heterogeneity of disease phenotypes.
Adenomatous Polyposis Coli↗
Transcripts with splicings of exons 15 and 16 of the hMLH1 gene in normal lymphocytes: implications in RNA-based mutation screening of hereditary non-polyposis colorectal cancer.
Germline mutations of the hMLH1 gene are estimated to account for a large fraction of kindreds affected by hereditary non-polyposis colorectal cancer (HNPCC). In a significant number of cases, hMLH1 mutations result in the expression of truncated proteins. We report here two novel alternatively spliced forms of hMLH1 mRNA in normal lymphocytes. One of these novel isoforms lacks the coding region of the gene between codons 557 and 578, corresponding to the entire exon 15. The deletion introduces a frameshift that results in a premature stop signal. The other isoform is characterised by an in-frame deletion spanning codons 578-632, corresponding to loss of the entire exon 16. Further studies are necessary to establish the biological significance of these alternative splicings. The presence of alternatively spliced hMLH1 transcripts that mimic pathogenic mutations should be taken into account in the mutational screening of the hMLH1 gene by reverse transcription-polymerase chain reaction methodologies.
Adaptor Proteins, Signal Transducing↗
Optimized PCR labeling in mutational and microsatellite analysis.
To optimize the labeling and visualization of PCR products we tested different variables, including deoxynucleotide concentration and ratio, dilution of labeled product, number of PCR cycles, and use of one-step or nested labeling protocols. Labeling was achieved using a fixed amount of labeled dATP, whose relative specific activity was varied by adding increasing amounts of cold dATP. Optimal PCR-labeling intensity was reached at dATP concentrations between 0.9 and 7.0 micromol/L, with a peak at 1.8 micromol/L. This concentration corresponded to an optimal ratio between the increase in specific activity and the decrease in DNA yield. Nucleotide imbalances >1:2 were not advantageous. Mutational analysis by single-strand conformational polymorphism (SSCP) was used to validate PCR-labeling protocols. The limiting nucleotide concentrations did not affect SSCP. Clear SSCP patterns were obtained using DNA templates of different sizes derived from several genes. SSCP patterns obtained using one-step or nested PCR-labeling protocols were equivalent and were visualized after overnight exposure, using [alpha35S]dATP as the label. Dilutions of labeled products ranging between 1:10 and 1:2.5 influenced SSCP patterns, and the lowest dilution tested produced better-defined and more-intense signals. Optimized SSCP conditions allowed the detection of novel and previously characterized nucleotide variants. Clear microsatellite typing was also obtained using optimized protocols and [alpha35S]dATP as the label.
Colorectal Neoplasms, Hereditary Nonpolyposis↗
[Prognostic value of neonatal pyelectasia diagnosed in utero].
Sixty-six children (48 male-18 female) with prenatal diagnosis of pyelectasia that was conformed at birth were examined between 1986-1994. All newborns carried out urinalysis and urine culture and performed a renal sonogram to reconfirm the diagnosis at 1 month of age. After 3 month of life the pelvic dilatation was confirmed in 61 patients while 5 showed a complete disappearance, 61 patients underwent micturitional cystography that evidenced 30 renal units (RU) with moderate to severe vesicoureteral reflux. In the patients without reflux, a scintigraphy was carried out with DTPA or MAG 3 and/or IVP and evidenced a functional junctional pathology in 32 RU and an organic junctional pathology in 24 RU, a primary megaureter with pre-vesical stenosis in 6 RU and a pyelo-ureteral complete double system in 4 RU. The patients with organic stenosis or those patients with parenchymal damage due to the vesicoureteral reflux underwent surgical intervention during the 1st year of life while all the remaining patients are continuously monitored to date with biohumoral exams and echography. With these results we can safely confirm the important role of the sonogram in the initial diagnosis of pyelectasia and to its eventual modifications in order to benefit the patients with a nephro-urological pathology and direct them toward a correct follow up.
Dilatation, Pathologic↗
von Willebrand factor and factor XIII in children with Henoch-Schonlein purpura.
levels of von Willebrand factor antigen (vWf:Ag) and factor XIII activity (F XIII) were studied in relation to the severity of clinical symptoms (scored from 0 to 3) and to immunological parameters [IgA, C3, C4, and circulating immune complexes (CIC)] in 16 children (7 males, 9 females, aged 3-11 years) with Henoch-Schonlein purpura (HSP) at presentation. vWf:Ag was increased in 7 patients, F XIII activity was decreased in 6. In all children we found high levels of IgA, while C3 and C4 levels were normal; CIC were elevated in 11. vWf:Ag correlated with clinical score and with IgA and CIC, probably as a result of immune-mediated endothelial cell damage. The haemostatic alterations observed in HSP are important for understanding the pathophysiology of the disease.
Acute Disease↗
Plasminogen activator activities in short-term tissue cultures of benign prostatic hyperplasia and prostatic carcinoma.
The high prevalence of prostatic carcinoma (PRCA) and the limited therapeutic possibilities provide a strong stimulus for exploring new approaches in experimental research that ultimately may lead to improved therapy. Indeed, methods for assessing carcinoma prognosis, such as clinical staging (clinical examination, ultrasound, and plasmatic levels of prostatic acid phosphatase and prostate specific antigen) and histopathological grading according to the Gleason score, usually fail to provide consistent predictive information regarding the clinical outcome of single tumors. Increased plasminogen activator (PA) activities have been associated with high-grade malignancies and with the potential for invasion/metastasis in many tumors. Urokinase-type plasminogen activator (uPA) is present in prostatic secretion, and an increased uPA activity has been noted in human prostatic cell lines with metastatic behavior. Unfortunately, any study of uPA production or gene regulation in primary tumors is complicated by the inherent mixture of host stromal cells, infiltrating macrophages, and subpopulations of tumor cells that may have variable metastatic capacity and ability to synthesize uPA. In short-term tissue culture of prostatic samples, it is possible to grow in vitro cancer prostatic epithelial cells and thus exclude the presence of contaminant cells. We have shown elsewhere that the levels of a type IV collagenase, 92-kDa matrix metalloproteinase, a protease involved in tumor progression and invasion, are increased in PRCA primary cell cultures if compared with benign prostatic hyperplasia (BPH) cell cultures (C. Festuccia et al., manuscript in preparation). Activation of matrix metalloproteinases also can be correlated with uPA expression; therefore we studied the expression of uPA in serum-free culture media of primary cultures of PRCA or BPH tissue samples.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
An adjustment method for spinal cord stimulators based on simplified gait analysis (1).
The use of electrical stimulators, for pain relief, spasticity reduction, and other applications, is greatly increasing; the programming facilities of the new devices extend the application range and allow to reduce the manufacturing costs. On the other side it is necessary to define methodologies and protocols for a custom setting of these devices. This work, although for only one patient, is a proposal for a methodology, based on a simplified gait analysis, for the adjustment of a spinal cord electrical stimulator.
Electric Stimulation Therapy↗
[Antithrombin III in infantile nephrotic syndrome].
In the Nephrotic Syndrome an hypercoagulable state can cause an increased incidence of thromboembolic phenomena and the course of the syndrome. The deficiency of Antithrombin III has been suggested to explain the hypercoagulability. We measured plasma antithrombin concentration (as percentage) in 24 children suffering from N.S. and the values were correlated with serum albumin, proteinuria and Partial Thromboplastin Time (PTT). The results of this study show that plasma Antithrombin III (AT-III) is significantly correlated with serum albumin, with proteinuria and PTT. Moreover plasma AT-III concentration was found to be low particularly when patients relapsed and in 2 children who developed thombophlebitis of the safena vein.
Adolescent↗
[Nifedipine in hypertensive emergencies in children].
Nifedipine is a calcium-antagonist whose principal action is reduction of peripheral resistance. The utilization of nifedipine is still limited in infancy. We have studied the immediate effect on hypertensive blood pressure values of nifedipine administered sublingually in 10 children (3 males and 7 females; aged 6-14 years) with different clinical diagnoses: acute glomerulonephritis (6 cases), lupus erythematosus systemicus (2 cases), membrane proliferative glomerulonephritis (1 case), pyelonephritis secondary to vesico-ureteral reflux (1 case). Nifedipine (0.25-0.50 mg/Kg) lowered systolic and diastolic blood pressure values from 167.5 +/- 19.8 mmHg and 103.5 +/- 18.4 mmHg to 126 +/- 19.8 mmHg and 81.5 +/- 15.1 mmHg, respectively, 30 minutes after administration (p less than 0.001). We propose nifedipine as a simple, effective and safe alternative drug for managing hypertensive emergencies in childhood.
Adolescent↗
[Gallium-67 scintigraphy in pneumoconiosis].
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Adult↗