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Biomedical subjects

A Ferrara

Publications and source records attributed to A Ferrara.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1989

[A method for identification of liver cirrhosis of alcoholic etiology].

There is a significant association between the pro capita alcohol consumption and cirrhosis mortality rate. Cirrhosis usually develops after years of excessive drinking, although in many alcoholic men it never develops, even after decades of drinking. The admission of large amounts of alcohol beverages is very difficult for many patients. This is a serious problem. In order to make easier the diagnosis in those patients, the authors have studied a composed, arbitrary score for alcoholism risk. The diagnosis with only laboratory findings was worse than that with an additional alcoholism risk score, in 48 cirrhotic patients with doubtful history of alcoholic etiology. The alcoholic risk score was based on presence/absence of: 1) car driving or working accidents; 2) familiar or love problems; 3) alcoholic relatives; 4) other alcohol-correlate disease; 5) job type.

Humans↗
PubMed1988

Effectiveness of neonatal transport in New York City in neonates less than 2500 grams--a population study.

In the past two decades, there has been a gradual trend to regionalization of perinatal care, categorization of hospitals and transport services for neonatal health care. The literature alludes to both beneficial and deleterious effects of neonatal transport (T) but no controls such as a matched nontransport (NT) population have been utilized to date. The major goal of this study was to evaluate the effect of neonatal transport from Level I and II high risk less than or equal to 2500 gm. neonates (born in NYC in one calendar year, 1979) compared to a cohort nontransported population matched for hospital of birth, weight, race, sex and risk. All transported less than or equal to 2500 gm. from Level I and II (n = 328) were studied and a stratified random sample of the nontransported (NT) infants less than or equal to 2500 gm. from these same hospitals (n = 2042) was used for comparison. The principle outcome variable was survival. The major conclusion of this study is that in Level I and II hospitals the transport group had a significantly increased survival in infants who were sick (Apgar less than 6) compared to cohorted nontransported controls. Interhospital differences in survival were noted among Level I and II but not seen in the subdivisions of (A) and (B) hospitals.

Demography↗
PubMed1988

Immunization of healthy adults with live attenuated varicella vaccine.

Live attenuated varicella vaccine was administered to healthy varicella-susceptible adults. Of 187 adults immunized with the Oka strain of vaccine, seroconversion to varicella-zoster virus (VZV) occurred in 82% after one dose and in 94% after two doses. Adverse effects were unusual. After immunization, one subject developed mild zoster caused by wild-type virus. Twelve adults developed a mild breakthrough case of chickenpox after exposure to VZV. Protection after household exposure was observed in nine (56%) of 16; however, the illness in all seven patients with breakthrough illness was modified, with an average of only 24 vesicles. Subjects seropositive at household exposure were unlikely to develop a breakthrough illness. Approximately 25% of vaccinees who seroconverted lost detectable antibodies to VZV after vaccination, but even those who became seronegative were partially protected. Varicella vaccine offered significant protection against severe chickenpox in healthy adults.

Adolescent↗
PubMed1988

Pathogenesis of postantibiotic diarrhoea caused by Clostridium difficile: an in vitro study in the rabbit intestine.

To elucidate the pathophysiological changes leading to postantibiotic diarrhoea caused by Clostridium difficile and its cytotoxin, oral ampicillin was given to rabbits, and jejunal, ileal, and caecal segments of those that developed diarrhoea were investigated in vitro. The rabbits that, in response to treatment, harboured Clostridium difficile in their colonic lumen were studied, and the results expressed according to the presence or absence of Clostridium difficile and/or its cytotoxin. Thus, we refer to either CD+ or CD- segments. The influx of glucose, phenylalanine, glycylphenylalanine, and lysine across the brush border of jejunum and ileum of CD+ segments was severely impaired, while only slightly blunted in CD-. No significant change was detected in the influx of glutamic acid in the jejunum of all treated animals and in the CD- ilea. Morphologic damage in ileum and caecum of CD+ was also more evident than in CD-. Transepithelial ion transport across short circuited ileal mucosa (CD+ and CD-) revealed secretory changes in Cl net transport that were more marked in CD-. We conclude that: (1) Clostridium difficile may also colonise the upper intestinal tract, where it induces morphological and functional damage, severely impairing nutrient absorption; and (2) the ileum contributes to the diarrhoea caused by CD even when the micro-organism is confined to the more distal gut by showing moderate impairment of nutrient absorption and marked electrolyte secretion.

Ampicillin↗
PubMed1988

Nizatidine and ranitidine in the short-term treatment of duodenal ulcer: a cooperative double-blind study of once-daily bedtime administration.

The aim of the present study was to assess the clinical efficacy and safety of a new H2-antagonist, nizatidine (N), administered as a single bedtime dose of 300 mg, compared with ranitidine (R) at the same dosage, in the short-term treatment of duodenal ulcer. One hundred forty one patients were included in the study: 70 were treated with N and 71 with R. During the study, three patients were withdrawn for unwanted effects not related to the treatment, and therefore, 69 patients per group were studied. After 4 wk of treatment, 58 patients treated with N (84.1%) and 55 in the group treated with R (77.5%), showed complete endoscopic ulcer healing (p greater than 0.5). The corresponding figure after 8 wk of therapy was 64 (94.2%) and 65 (94.2%) (p greater than 0.5). A similar effect on pain relief was observed: 42% of patients in both groups became asymptomatic after 4 wk. After 8 wk, the percentage rose to 84.2% in the group treated with N and 87.0% in the R group (p greater than 0.5). In both groups, only minor side effects occurred, not requiring drug discontinuation. These data show that nizatidine in a single bedtime dose of 300 mg is as effective and safe as ranitidine at the same dosage, and represents therefore a valid alternative to the usual H2-antagonists.

Adolescent↗
PubMed1988

Bilirubin in cerebrospinal fluid: an indicator of blood-brain barrier disruption in asphyxiated rats.

To evaluate the relationship of serum cerebrospinal fluid (CSF) and brain total bilirubin levels in asphyxia, an experiment was designed with 5 to 6-week-old Sprague-Dawley rats. The rats were randomized into control and experimental groups. All rats received intravenously 30 mg/kg of bilirubin. Four hours later the experimental group was asphyxiated. Forty-eight hours after asphyxiation, the bilirubin concentrations in blood, CSF, and brain were measured in both study groups. Mean CSF and brain bilirubin levels were significantly higher in the experimental compared to the control group; however, mean serum bilirubin levels were not different. Moreover, in the experimental group a significant correlation existed between CSF and brain bilirubin concentrations. In conclusion, an asphyxiatic insult resulted in disruption of both the blood-brain and the blood-CSF barriers.

Animals↗
PubMed1988

Penetration of roxithromycin in bronchial secretions.

Roxithromycin sputum and serum concentrations after administration of therapeutic doses (150 mg in a single dose) were evaluated in six patients. Blood samples and pooled sputum samples were collected at corresponding time intervals up to 24 h after drug administration. Roxithromycin sputum levels were found to be almost always above serum concentrations, the highest sputum levels being 5.85 +/- 2.5 micrograms/ml in the interval ranging from 2 to 4 h after drug administration. Due to its antibacterial spectrum and favourable pharmacokinetic properties, roxithromycin, like other macrolide antibiotics, seems to be particularly indicated in the treatment of respiratory tract infections.

Age Factors↗
PubMed1988

[Influence of posture in respiratory function examination of obese subjects. I. In the healthy subject without ventilation disorders].

On earlier occasions healthy subjects, and chronic bronchopneumopathy patients were subjected to respiratory function tests in different postures using the plethysmographic and helium dilution methods. This protocol was then applied to a series of obese patients without the functional characteristics of alveolar hypoventilation identified in preliminary functional tests. The study revealed: a) non significant differences between plethysmographic and helium dilution findings; b) no significant volumetric differences produced by different postures (standing or squatting) especially as far as Total Lung Capacity is concerned. These results confirm the findings of others (Sharp et al., 1986) that diaphragmatic adjustment to changes in posture is inadequate in the obese even in the absence of hypoventilation.

Adult↗