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Biomedical subjects

A Ferrara

Publications and source records attributed to A Ferrara.

At least 19 recordsLinked to original sources
PubMed1995

Lipoprotein(a) concentrations in non-insulin-dependent diabetes mellitus and borderline hyperglycemia: a population-based study.

The objective of the study was to compare lipoprotein(a) [Lp(a)] concentrations in population-based samples of individuals with non-insulin-dependent diabetes mellitus (NIDDM), borderline hyperglycemia, and normoglycemia. From 2,740 male Italian Telephone Company employees aged 40 to 59 years participating in a health screening, we selected all those with NIDDM (n = 100) plus a random sample of 950 nondiabetic individuals. Diabetes was defined as fasting plasma glucose (FPG) of at least 140 mg/dL or current use of hypoglycemic drugs. Among nondiabetic individuals, 854 were defined as normoglycemic (FPG < 115 mg/dL) and 95 were defined as borderline hyperglycemic (115 < FPG < 140 mg/dL). Lp(a) level was measured on frozen plasma by enzyme-linked immunosorbent assay. Lp(a) concentrations were similar in people with NIDDM, borderline hyperglycemia, and normoglycemia: 11.2 +/- 14, 14.1 +/- 20, and 13.9 +/- 18 mg/dL, respectively (F = 1.03). Accordingly, the proportion of subjects with Lp(a) levels of at least 30 mg/dL was comparable in the three groups (12%, 15%, and 14%; chi 2 = 3.95, P = .41). Results were not confounded by differences in age, body mass index (BMI), waist to hip ratio, plasma lipids, alcohol consumption, physical activity, and use of drugs. Furthermore, within the diabetic group Lp(a) levels were not significantly different for those on diet only versus those on oral agents (10.8 +/- 14.1 v 11.7 +/- 14.7, P = .7) or for people with FPG of at least 180 as compared with people with FPG less than 180 mg/dL (9.9 +/- 12.8 v 11.5 +/- 14.8, P = .5).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Cloning and sequence analysis of a rapamycin-binding protein-encoding gene (RBP1) from Candida albicans.

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.

Amino Acid Sequence↗
PubMed1992

Preservation of continence after ileoanal anastomosis by the coordination of ileal pouch and anal canal motor activity.

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.

Adult↗
PubMed1992

Epidemiology of diabetes mellitus in southern Italy: a case-finding method based on drug prescriptions.

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)

Adolescent↗
PubMed1992

NIDDM associated with mutation in tyrosine kinase domain of insulin receptor gene.

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.

Alleles↗
PubMed1991

The CYP2 gene of Saccharomyces cerevisiae encodes a cyclosporin A-sensitive peptidyl-prolyl cis-trans isomerase with an N-terminal signal sequence.

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.

Amino Acid Isomerases↗
PubMed1991

Secretion of N-glycosylated interleukin-1 beta in Saccharomyces cerevisiae using a leader peptide from Candida albicans. Effect of N-linked glycosylation on biological activity.

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.

Amino Acid Sequence↗
PubMed1991

[Production of mutagenic compounds during the water purification treatment of surface water].

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)

Carcinogenicity Tests↗
PubMed1991

[Pulp necrosis following prosthetic-periodontal treatment of vital teeth].

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%).

Dental Abutments↗
PubMed1990

Effect of cholecystokinin receptor blockade on human lymphocyte proliferation.

Cholecystokinin is a peptide produced by neuroendocrine cells in gut and neurons in brain and gut. Proliferating human peripheral blood mononuclear cells (H-PBMC) also make small amounts of cholecystokinin. Cholecystokinin increases intracellular calcium (Ca2+) in H-PBMC. This can be blocked with L 364, 718, a non-toxic specific cholecystokinin antagonist. Cholecystokinin is a comitogen for H-PBMC and activates H-PBMC in a cyclosporine-resistant fashion. If cholecystokinin is a critical lymphokine, then L 364, 718 should block H-PBMC mitogenesis. H-PBMC from healthy donors were stimulated in vitro with either phytohemagglutinin or anti-CD3 monoclonal antibody. L 364, 718 was not toxic for H-PBMC, yet inhibited mitogenesis at 10(-7), 10(-6), and 10(-5) M. The small amount of cholecystokinin made by H-PBMC may play a critical role in H-PBMC mitogenesis.

Antibodies, Monoclonal↗
PubMed1990

Hypothermia and acidosis worsen coagulopathy in the patient requiring massive transfusion.

Massive transfusion may cause abnormalities of electrolytes, clotting factors, pH, and temperature and may occur in a scenario of refractory coagulopathy and irreversible shock. Identification of correctable variables to improve survival is complicated by the interplay of this pathophysiology. Temperature may be an under-appreciated problem in the genesis of coagulopathy. In vitro studies have demonstrated that platelet function and vascular response are critically temperature-dependent. We reviewed the records of 45 trauma patients without head injury or co-morbid medical illness who required massive transfusions. The mean Injury Severity Score was 55 +/- 6, a mean of 22.5 +/- 5 units of blood was transfused, and mortality was 33%. Nonsurvivors were more likely to have had penetrating injury (88% versus 55%), received more transfusions (26.5 +/- 9 versus 18.6 +/- 1, p less than 0.05), had lower pH (pH 7.04 +/- 0.06 versus 7.18 +/- 0.02, p less than 0.05), had lower core temperature (31 +/- 1 degree C versus 34 +/- 1 degree C, p less than 0.01), and had a higher incidence of clinical coagulopathy (73% versus 23%). Severe hypothermia (temperature less than 34 degrees C) occurred in 80% of the nonsurvivors and in 36% of survivors. Patients who were hypothermic and acidotic developed clinically significant bleeding despite adequate blood, plasma, and platelet replacement. Avoidance or correction of hypothermia may be critical in preventing or correcting coagulopathy in the patient receiving massive transfusion.

Acidosis↗
PubMed1989

Bactericidal activity of meropenem and interactions with other antibiotics.

MICs of meropenem for selected clinical isolates of bacteria were determined. Killing curves were performed on strains of methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staph. aureus (MRSA), methicillin-resistant Staph, epidermidis, Escherichia coli, Klebsiella spp., Enterobacter cloacae, Pseudomonas aeruginosa, Citrobacter freundii and Acinetobacter spp. A reduction of greater than or equal to 3 x log10 in viable cells was observed at 4 and 6 h of exposure to 4 and 8 x MIC, and this was usually maintained at 24 h (with a few exceptions for methicillin-resistant Staph, epidermidis and Ent. cloacae). At the MIC and twice the MIC regrowth tended to occur at 24 h although this varied from strain to strain. The interaction with other antibiotics was determined by the chequerboard technique. Usually an additive or synergistic effect was observed when meropenem or imipenem was used in combination with an aminoglycoside against Gram-negative species, while in a few cases antagonism occurred in combination with beta-lactams. Against Staph, aureus, MRSA and Staph, epidermidis synergism was usually obtained with combinations with teicoplanin or vancomycin and either synergism or addition with combinations with rifampicin, co-trimoxazole or ciprofloxacin.

Anti-Bacterial Agents↗
PubMed1989

[Serum concentration of bile acids and portal hypertension in cirrhotic patients. Possible correlations].

For the detection of mild liver disease (acute viral hepatitis, chronic persistent hepatitis, fatty liver) serum bile acids levels have not proved to be superior to transaminases or other common liver tests with almost similar sensitivity and/or specificity. Indeed it has been possible to show in patients with compensated cirrhosis of the liver that the serum bile acids concentration is related to the degree of intrahepatic shunts and that there was a significant relationship between the fasting serum bile acids and the intrinsic clearance of ICG. Measurement of serum bile acids appear to be more sensitive for detection of cirrhosis than commonly used tests. The elevation of bile acids concentration in cirrhotic patients is thought to result from a reduced hepatic clearance and/or from portosystemic shunting. In order to determine the role of serum bile acid estimation in the indirect assessment of portal hypertension, fasting and two-hour postprandial serum bile acids concentration were measured in 36 patients with liver cirrhosis, classified according to Child-Pugh's criteria. Real time ultrasonography, esophagogastroscopy and static liver scintigraphy of the liver were carried out in all patients. The size of esophageal varices, the portal vein and its related structure, the nuclear criteria were graded according to the common methods. Between the clinical findings, splenomegaly, was noted and graded, though the size of spleen does not correlate well with the level of portal pressure. In our patients a good correlation (p less than 0.001) existed between the two hour postprandial bile acids concentration and ultrasonographic findings of portal hypertension. Fasting serum bile acids (SBA) were significantly higher in severe than in mild liver cirrhosis according to Pugh's criteria (p less than 0.001). In conclusion we think that SBA concentrations have a great prognostic value in assessment of major complications (upper gastrointestinal hemorrhage particularly). The reduced liver blood flow, for intra-and extrahepatic porto-systemic shuntings, is probably the main cause of reduced hepatic clearance of bile acids.

Adult↗