[Rhinobronchial syndrome].
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Biomedical subjects
Publications and source records attributed to A Ferrara.
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The great importance of knowing the risk factors for breast pathology in order to reveal the risk categories is well known. In many geographical areas breast cancer is the most common female neoplasm. Recent Italian statistics point out that every year 83 women out of 100,000 develop breast cancer and that its incidence is increasing. Every year in Italy 10,000 women die of breast cancer. In our retrospective study 146 women suffering from breast cancer, treated in our Institute from 1970 to 1993, were enrolled. We excluded 4 patients, surgically treated in another Institute and 35 who presented a second or a third gynaecological cancer. We considered age, menarche, parity and menopausal age in all patients in order to evaluate the association of these risk factors with breast cancer development. The average age when neoplasm was first diagnosed was 53.07 years (between 30-84 years), with a 9.4% incidence in patients under 35 years old. In 41.1% of the cases, menarche was present under 12 years and in only 14.1% after 14 years, therefore confirming the reduction of mammary cancer risk in women with late menarche. Twenty one point five per cent of the patients were nulliparous. In our case series no protective factor seemed to be related with 1 or 2 pregnancies (43.9%). The menopausal average age was 50.2, with an average fertile life period of 37.1 years. Our study also considered the location of the primary neoplasia (60.7% in the upper-outer quadrant), the tumor size (3.08 cm average diameter) and the histological type (81.3% ductal form).(ABSTRACT TRUNCATED AT 250 WORDS)
The anal sphincters facilitate fecal continence by maintaining a pressure barrier; whether proximal contractile events influence this barrier is unknown. The aim of this study was to determine whether a relationship exists between anal canal pressures and rectal motor activity. A fully ambulatory system for prolonged pressure recording was developed. In 12 healthy subjects (seven males and five females; mean age, 35 years; range, 22-43 years), a flexible transducer catheter (outside diameter, 4.5 mm) was introduced endoscopically such that sensors were 2, 3, 8, 12, 18, and 24 cm from the anal orifice. Twenty-four-hour spontaneous motor activity was stored in a 2.5-megabyte portable recorder for later transfer to a Microvax II for computerized analysis and display. Mean anal canal pressure was calculated, and rectal motor complexes (RMCs) were characterized. Mean and canal resting pressure was 75 +/- 12 mmHg. During sleep, anal pressures displayed cyclic decreases (mean periodicity, 1.6 hours; range, 1-4 hours), during which the mean +/- SD pressure trough was 15 +/- 4 mmHg (range, 8-21 mmHg). RMCs were identified in all subjects: mean frequency, 16 per 24 hours (range, 12-22 per 24 hours); duration, 15.3 minutes (range, 8-35 minutes); contractile frequency, two to three per minute; mean peak amplitudes, 58 +/- 18 mmHg; and periodicity, 78 +/- 24 minutes (range, 35-265 minutes). Importantly, an RMC was invariably accompanied by a rise in mean anal canal pressure and contractile activity such that pressure in the anal canal was always greater than pressure in the rectum. Anal canal relaxations never occurred during an RMC. Motor activities of the rectum and of the anal canal may be related; the onset of rectal contractions was accompanied by increased resting pressure and contractile activity of the anal canal. This temporal relationship represents an important mechanism preserving fecal continence.
Plasma and platelet levels of excitatory amino acids were measured in 38 psychiatric out-patients and in 19 comparison subjects; the patients had DSM-III-R diagnoses of organic mental disorders (N = 3), mood disorders (N = 15), schizophrenia (N = 13), and anxiety disorders (N = 7). The glutamate plasma levels were significantly higher in the patients with mood disorders than in the comparison group.
Insulin action was investigated in cultured skin fibroblasts from two consanguineous patients with a heterozygous point mutation in the insulin receptor kinase (Arg1152-Gln). In spite of normal binding, Gln1152 insulin receptor exhibited 20% increased basal kinase activity, but significantly reduced insulin-dependent autophosphorylation and kinase activity compared to controls from either weight-matched noninsulin-dependent diabetic patients (n = 4) or normal subjects (n = 5). In fibroblasts from the mutant patients, basal alpha-aminoisobutyric acid and 2-deoxyglucose (2-DG) uptake, cytochalasin-B (CB) plasma membrane binding, and glycogen synthase activity were increased to levels similar to those in maximally insulin-stimulated control cells. No insulin stimulation of these metabolic effects was detected in the mutant cells. In spite of the high basal 2-DG uptake and CB binding and the lack of further insulin response, fibroblasts from the mutant patients responded to 12-O-tetradecanoylphorbol-13-acetate with a further 50% increase in 2-DG uptake and CB binding. The magnitude of the effects of insulin and 12-O-tetradecanoylphorbol-13-acetate in control cells were nearly identical. We conclude that the Gln1152 insulin receptor impairs insulin regulation of metabolic responses in patient cells. Its presence in fibroblasts from the mutant patients appears to be accompanied by an increased pool of glucose transporters.
The data are preliminary findings in order to study the possible pollution of fresh olive oil with Class I Pesticides, often misused by olive farmers, and it's effect on children's health. The oil produced from the olives of 8 farms in a small town of Southern Italy was collected at the mill in 1992, with no previous notice to the farmers, and was analyzed by Head Space Gas Chromatographic technique. The research for organophosphates and chlorinated pesticides was negative. The Kreis test excluded oil rancidity and the index of refraction confirmed the oils being fresh olive oil. The fact that the oil samples resulted free of pesticide residuals, however, might be explained by the unusual season weather not favourable to the olive parasites and the consequent reduced amounts of pesticides used by the farmers. The work will be repeated in 1993 and completed by a dietary semiquantitative questionnaire and epidemiologic evaluations on the children's health.
Three experiments investigated memory for stimulus duration in humans using a modification of a delayed-matching technique previously used to study event memory in pigeons. In a session of 48 discrete trials subjects were presented with a sample stimulus (a 500-Hz tone with mean duration of 400 msec) then a comparison stimulus (the same duration as the sample, or longer or shorter), after a delay that was 1 to 10 sec in Experiments 1 and 2, and 2 to 16 sec in Experiment 3. After the comparison had been presented, subjects judged whether the sample and comparison had the same duration (a YES/NO decision, Experiment 1), or whether the comparison was longer, shorter, or of the same duration as the sample (Experiments 2 and 3). Overall, mean number of correct responses changed little with increases in the delay, but the change of number of correct responses with delay was markedly different on trials in which the sample and comparison were the same, the comparison was shorter, or the comparison was longer. In general, accuracy decline with increasing delay in the first case, remained constant in the second case, and increased when the comparison was longer than the sample. Examination of the types of errors made on the different sorts of trials (Experiment 3) suggested that the data were produced by two mechanisms: (1) subjective shortening of the sample as the delay between sample and comparison increased, and (2) a time-order error to respond that the sample was longer than the comparison. Overall, it appears that humans' working memory for duration exhibits a subjective shortening effect similar to that previously found in pigeons.
Rapamycin (Rm) and FK506 are macrolide antifungal agents that exhibit potent immunosuppressive properties in higher eukaryotes which are mediated through interaction with specific receptor proteins (FKBPs or RBPs, for FK506- and Rm-binding proteins, respectively). These proteins possess peptidyl-prolyl cis-trans isomerase (PPIase) activity in vitro which is inhibited by the binding of Rm and FK506. We previously isolated a gene encoding an RBP from Saccharomyces cerevisiae, and demonstrated that null mutations in this gene (called RBP1) result in a recessive Rm-resistant (RmR) phenotype. We now have cloned the Candida albicans RBP1 gene via complementation of the RmR phenotype in S. cerevisiae. The predicted C. albicans RBP exhibits 61%, 52% and 49% amino acid (aa) sequence identity with RBPs (FKBPs) from S. cerevisiae, Neurospora crassa and human cells (FKBP-12), respectively. Furthermore, several of the aa residues identified as being important for drug binding in human FKBP-12 are conserved within the C. albicans RBP.
Nocturnal incontinence may occur after ileoanal anastomosis and may be related to loss of an effective anal canal pressure barrier during sleep; how pressure and contractions in the proximal bowel influence this barrier is unknown. Our aim was to evaluate the relationship between anal canal pressure and contractions and contractile activity of the pouch in continent subjects after ileal pouch-anal anastomosis (IPAA) and of the rectum in normal controls. A fully ambulatory system for 24-hour pressure recording was used. A flexible transducer catheter was introduced endoscopically so that sensors were at 2, 3, 8, 12, 16, and 24 cm from the anal orifice in 12 healthy controls (7 men, 5 women, mean age: 35 years) and 7 fully continent IPAA patients (4 men, 3 women, mean age: 34 years) more than 12 months postoperatively. Twenty-four hour spontaneous motor activity was stored in a 2.5 megabyte (MB) digital portable recorder. Mean anal canal pressure was calculated, and rectal motor complexes and ileal pouch large pressure waves were characterized. During sleep, resting anal canal pressures were similar in the two groups (72 +/- 12 mm Hg in controls versus 66 +/- 9 mm Hg in IPAA patients [mean +/- standard deviation (SD)], p = NS), but anal canal pressure showed cyclic relaxations (periodicity: 95 +/- 11 min in controls, 54 +/- 18 min in IPAA patients, p less than 0.05), during which the mean pressure trough was 15 +/- 4 mm Hg in controls and 14 +/- 5 mm Hg in IPAA patients (p = NS). In the control patients, during sleep, a mean of six rectal motor complexes were identified (range: 3 to 9). In patients with IPAA, during sleep, a mean of eight large pressure waves per hour were identified (range: 2 to 20). Importantly, in both controls and patients, rectal motor complexes or large pressure waves were always accompanied by rapid return of anal canal pressure from trough to basal values and increased contractile activity. We concluded that, in healthy patients and in continent patients after IPAA, motor activity of the rectum and of the ileal pouch was associated with changes in pressure and contractile activity of the anal canal so that rectal- and neorectal-anal canal pressure gradient, and, in turn, fecal continence were preserved.
The study evaluates whether data concerning drug prescriptions available from the National Health System (NHS) can be used to provide an estimate of the prevalence and pattern of treatment of diabetes in a well defined health district in southern Italy. In Italy virtually all drug prescriptions are obtained through the NHS. For a period of three consecutive months all prescriptions of insulin, hypoglycemic agents and strips for blood and urine testing were monitored in a well defined area near Naples. 2958 cases were thus identified giving a prevalence of drug treated diabetes mellitus of 2.01%; prevalence was higher in females than in males (2.68 vs 1.35%) and increased with age from 0.05% in the age group below 9 years to 13.67 in the age group over 70 years. This case-finding procedure was validated by cross-check with independent sources of cases. To evaluate the sensitivity of the method a list of 820 "known" cases of drug treated diabetes mellitus was obtained from a random sample of local general practitioners (GPs) and diabetic clinics: 73.5% of these cases were also detected through the analysis of drug prescriptions. To evaluate the probability of misclassification a random subsample of 602 cases identified through prescriptions was submitted to the GPs working in the study area, for 517 the diagnosis of diabetes was confirmed, thus yielding a positive predictive value of 85.9%. After correction for sensitivity and probability of misclassification the prevalence of drug treated diabetes in our population was 2.52%. The pattern of prescriptions in this population is also given.(ABSTRACT TRUNCATED AT 250 WORDS)
A population of 103 patients with non-insulin-dependent diabetes mellitus (NIDDM) was screened for mutations in the tyrosine kinase domain of the insulin receptor gene. Patient genomic DNAs corresponding to exons 17-21 of the insulin receptor gene have been amplified by polymerase chain reaction and analyzed by denaturing gradient gel electrophoresis (DGGE). One patient was identified with an altered pattern of mobility of exon 20 in the DGGE assay. Direct sequence of amplified DNA showed a single nucleotide substitution in the codon 1152 (CGG-- greater than CAG), resulting in the replacement of Arg with Gln. Two bands appeared in the sequence of exon 20 of the insulin receptor (nucleotide position 3584), indicating that this patient was heterozygous for the mutation. Insulin binding to intact erythrocytes from the patient was in the normal range. Although autophosphorylation of the purified insulin receptor also seemed normal, its kinase activity toward the exogenous substrate poly Glu:Tyr (4:1) was undetectable. This mutation may impair insulin receptor kinase and contribute to insulin resistance in this patient.
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Cells of Saccharomyces cerevisiae contain a major cytosolic cyclophilin (Cyp)-related peptidyl-prolyl cis-trans isomerase (PPIase) which is the target for cyclosporin A (CsA) cytotoxicity and which is encoded by the CYP1 gene [Haendler et al., Gene 83 (1989) 39-46]. We recently identified a second Cyp-related gene in yeast, CYP2 [Koser et al., Nucleic Acids Res. 18 (1990) 1643] which predicts a protein with a hydrophobic leader sequence. A sequence lacking 33 codons from the 5'-end of the CYP2 open reading frame was generated by the polymerase chain reaction and engineered for expression in Escherichia coli. The corresponding recombinant truncated protein was purified and found to exhibit PPIase activity which was inhibited by CsA. The CYP2 gene is genetically unlinked to CYP1. As with CYP1, genomic disruption of CYP2 had no effect on haploid cell viability. Disruption of all three of the known yeast PPIase-encoding genes [CYP1, CYP2, and RBP1 for rapamycin-binding protein; Koltin et al., Mol. Cell. Biol. 11 (1991) 1718-1723] in the same haploid cell also resulted in no apparent cellular phenotype, suggesting either that none of these enzymes have an essential function or that additional PPIases can compensate for their specific absence. Whereas cells containing a genomic disruption of CYP1 exhibited a CsA-resistant phenotype, genomic disruption of CYP2 had no effect on CsA sensitivity. This suggests that the CYP1 gene product is the primary cellular target for CsA toxicity in yeast. Since both purified Cyps display CsA sensitivity in vitro, our data suggest that Cyp1 and Cyp2 differ in terms of their cellular function and/or localization.
Human interleukin-1 beta (IL-1 beta) is expressed in activated monocytes as a 31-kDa precursor protein which is processed and secreted as a mature, unglycosylated 17-kDa carboxyl-terminal fragment, despite the fact that it contains a potential N-linked glycosylation site near the NH2 terminus (-Asn7-Cys8-Thr9-). cDNA coding for authentic mature IL-1 beta was fused to the signal sequence from the Candida albicans glucoamylase gene, two amino acids downstream from the signal processing site. Upon expression in Saccharomyces cerevisiae, approximately equimolar amounts of N-glycosylated (22 kDa) and unglycosylated (17 kDa) IL-1 beta protein were secreted. The N-glycosylated yeast recombinant IL-1 beta exhibited a 5-7-fold lower specific activity compared to the unglycosylated species. The mechanism responsible for inefficient glycosylation was also studied. We found no differences in secretion kinetics or processing between the two extracellular forms of IL-1 beta. The 17-kDa protein, which was found to lack core sugars, does not result from deglycosylation of the 22-kDa protein in vivo and does not result from saturation of the glycosylation enzymatic machinery through overexpression. Alteration of the uncommon Cys8 residue in the -Asn-X-Ser/Thr-glycosylation site to Ser also had no effect. However, increasing the distance between Asn7 and the signal processing site increased the extent of core N-linked glycosylation, suggesting a reduction in glycosylation efficiency near the NH2 terminus.
In the last years many studies have reported the presence of mutagenic/carcinogenic compounds in treated waters. These substances can be present in raw water, but are also produced during drinking water purification. Mutagens are formed as by-products of chemical reactions between oxidants/disinfectants used in treatments and organic load of the raw water (humic and fulvic acids). The aim of this study was to evaluate the production of mutagenic substances during the main phases of the Po river water treatment ("PO3" plant) in Turin. Water samples (50 litres), collected from February 1989 to August 1990, were concentrated with XAD-2/XAD-8 resins mixture. Extracts were tested for mutagenicity at different doses (1, 2.5, 5 and 10 litres) by Ames Salmonella assay, using TA 100 and TA 98 strains, without microsome fraction (S9). Raw water was rarely mutagenic while, in particular at the highest doses (5 and 10 litres), sometimes showed toxic effect. After ozonation treatment only few samples were mutagenic with TA 100 strain, while 43% of the samples were mutagenic with TA 98. The following treatment of clariflocculation and chlorination with NaClO produced mutagens in 95% of the samples assayed with TA 100 and in 85% of the samples assayed with TA 98. The next GAC/sand filtration step seems to reduce the mutagenic load produced in the previous phases. Finally, drinking water after chlorination with ClO2 showed weak mutagenicity at 1 litre dose (26% and 21% of positive samples with TA 100 and TA 98 respectively) and this effect increased at the higher dosages.(ABSTRACT TRUNCATED AT 250 WORDS)
This study investigated the frequency of periapical lesions following pulpal necrosis in vital teeth used as abutments in periodontal-prosthetic therapy. The study was conducted on a continuative series of 1000 teeth treated at least 2 years before the start of the investigation. 500 teeth were treated by specialist and 500 by general practitioners. The dental records of this sample were stored into a computer, analyzed and compared, and the chi-square index was calculated. Periapical lesions were found in 22.6% of the teeth. Maxillary incisors had the highest number of lesions (36.8%). The percentage of lesions increased as periodontal involvement became more severe (37.2%) with severe involvement as opposed to 18.5% with moderate involvement). The frequency of lesions was lower in the group of teeth treated by specialists than in the group treated by general practitioners (13.8% as opposed to 31.4%).
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