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Biomedical subjects

C Santini

Publications and source records attributed to C Santini.

At least 19 recordsLinked to original sources
PubMed2001

Export of Thermus thermophilus alkaline phosphatase via the twin-arginine translocation pathway in Escherichia coli.

The bacterial twin-arginine translocation (Tat) pathway is distinct from the Sec system by its remarkable capacity to export folded enzymes. To address the question whether the two systems are capable of translocating homologous enzymes catalyzing the same reaction, we cloned the tap gene encoding Thermus thermophilus alkaline phosphatase (Tap) and expressed it in Escherichia coli. Unlike the alkaline phosphatase of E. coli, which is translocated through the Sec system and then activated in the periplasm, Tap was exported exclusively via the Tat pathway and active Tap precursor was observed in the cytoplasm. These results demonstrate that two sequence and functional related enzymes are exported by distinct protein transport systems, which may play an integral role in the bacterial adaptation to their environment during the evolution.

Alkaline Phosphatase↗
PubMed2001

Dysphagia in a patient with Wegener's granulomatosis: case report.

Wegener's Granulomatosis is an autoimmune disease characterized by a rare form of systemic vasculitis which can result in damage to vital organs of the body by restricting blood flow to those organs. It affects various systems of the body including the central nervous system and cranial nerves. To our knowledge, there are no previous described cases of oropharyngeal dysphagia in these patients. This paper describes and discusses a case of oropharyngeal dysphagia in a patient with Wegener's Granulomatosis.

Aged↗
PubMed2001

Impairment of cardiac autonomic function in patients with Duchenne muscular dystrophy: relationship to myocardial and respiratory function.

BACKGROUND: Previous studies reported an impairment of nervous autonomic activity in patients with Duchenne muscular dystrophy (DMD). However, the relationship of the autonomic dysfunction to the impairment of cardiac mechanical function and of respiratory failure is not completely understood. METHODS: We evaluated cardiac autonomic function by time- and frequency-domain heart rate variability (HRV) analysis on 24-hour Holter recordings in 60 patients with DMD (16.8 +/- 4.8 years) and 28 healthy control patients (15.2 +/- 4.6 years, P = not significant). The circadian rhythm of R-R interval, low frequency, high frequency, and low-frequency/high-frequency ratio was also assessed. In all patients, left ventricular ejection fraction was measured by 2D echocardiography; respiratory function was assessed by spirometry. RESULTS: All HRV parameters were lower in patients with DMD than in control subjects, with the percentage of differences between adjacent R-R intervals >50 ms (11.6% +/- 8.5% vs 27.3% +/- 14.1%, P =.00001) and high frequency (23.9 +/- 10.3 ms vs 36.1 +/- 12.2 ms, P =.0001) showing the strongest differences. A significant circadian rhythm of HRV variables was present in both groups, but it was considerably flattened in patients with DMD. There was no correlation between left ventricular ejection fraction and HRV indexes except for a weak correlation with high frequency (r = 0.30, P =.02) and with low-frequency to high-frequency ratio (r = -0.29, P <.03). Similarly modest correlations were found between forced vital capacity and high frequency (r = 0.4, P =.007) and low-frequency/high-frequency ratio (r = -0.32, P =.026). Multiple regression analysis did not show any independent predictive variable for the autonomic impairment. CONCLUSIONS: Our data show a marked impairment of cardiac autonomic function in patients with DMD, which appears to mainly involve the parasympathetic branch and appears to have a multifactorial origin.

Adolescent↗
PubMed2001

The role of preoperative Tc-99m HMPAO-labeled leukocyte total-body scans in aortic prosthetic reconstruction.

PURPOSE: This study was performed to evaluate the utility of Tc-99m HMPAO-labeled leukocyte total-body scans (TBLS) for detecting remote septic foci before operation in patients undergoing aortofemoral vascular surgery. MATERIALS AND METHODS: Fifty-eight patients were screened before operation for inflammatory or infective disease, and a clinical score was assigned to each patient. Each patient had TBLSs. The relation between the clinical score and the TBLS result was determined. Patients with positive results of the TBLSs were examined, and the causes of these findings were treated before surgery. RESULTS: Ten of the 58 (17%) patients had a positive result of TBLSs. Of 31 patients with a clinical score of zero, 3 had positive findings of TBLS. No TBLS was positive in the 13 patients with a clinical score of 1. TBLS findings were positive in 7 of 14 of the combined patients with clinical scores of 2, 3, or 4. None of the patients showed signs of prosthetic vascular graft infection during the postoperative follow-up period. CONCLUSIONS: In conclusion, TBLSs can be used before aortofemoral vascular surgery, but only in patients with high clinical scores for inflammatory or infective disease to identify relevant infective foci that could cause vascular graft infection.

Aged↗
PubMed2000

Activation of PPARdelta alters lipid metabolism in db/db mice.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors, which heterodimerize with the retinoid X receptor and bind to peroxisome proliferator response elements in the promoters of regulated genes. Despite the wealth of information available on the function of PPARalpha and PPARgamma, relatively little is known about the most widely expressed PPAR subtype, PPARdelta. Here we show that treatment of insulin resistant db/db mice with the PPARdelta agonist L-165041, at doses that had no effect on either glucose or triglycerides, raised total plasma cholesterol concentrations. The increased cholesterol was primarily associated with high density lipoprotein (HDL) particles, as shown by fast protein liquid chromatography analysis. These data were corroborated by the chemical analysis of the lipoproteins isolated by ultracentrifugation, demonstrating that treatment with L-165041 produced an increase in circulating HDL without major changes in very low or low density lipoproteins. White adipose tissue lipoprotein lipase activity was reduced following treatment with the PPARdelta ligand, but was increased by a PPARgamma agonist. These data suggest both that PPARdelta is involved in the regulation of cholesterol metabolism in db/db mice and that PPARdelta ligands could potentially have therapeutic value.

Acetates↗
PubMed2000

Sternal wound infection revisited.

Sternal wound infections (SWIs) can be subdivided into two types, superficial or deep, that require different treatments. The clinical diagnosis of superficial SWI is normally easy to perform, whereas the involvement of deep tissues is frequently difficult to detect. Therefore, there is a need for an imaging study that permits the assessment of SWIs and is able to distinguish between superficial and deep SWI. The present work was a prospective study aiming to evaluate the role of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) labelled leucocyte scan in SWI management. Twenty-eight patients with suspected SWIs were included in the study. On the basis of clinical examination they were subdivided into three groups: patients with signs of superficial SWI (group 1), patients with signs of superficial SWI and suspected deep infection (group 2) and patients with suspected deep SWI without superficial involvement (group 3). Ten patients previously submitted to median sternotomy, but without suspected SWI, were also included in the study as a control group (group 4). All patients with suspected SWI had bacteriological examinations of wound secretion, if present. In addition 99mTc-HMPAO labelled leucocyte scan was performed in all patients. The patients of groups 1, 2 and 3 were treated on the basis of the clinical signs and microbiological findings, independently of the scintigraphic results. The patients of group 4 did not receive treatment. The final assessment of infection was based on histological and microbiological findings or on long-term clinical follow-up. Sensitivity, specificity, accuracy and positive and negative predictive values for scintigraphic and non-scintigraphic results were calculated. In the diagnosis of superficial and deep SWI, clinical and microbiological examination (combined) yielded, respectively, a sensitivity of 68.7% and 100%, a specificity of 77.3% and 80.8%, an accuracy of 73.7% and 86.8%, a positive predictive value of 68.7% and 70.6% and a negative predictive value of 77.3% and 100%. The scintigraphic results obtained in superficial SWI yielded a sensitivity of 56.2%, a specificity of 90.9%, an accuracy of 76.3%, a positive predictive value of 81.8% and a negative predictive value of 74.1%, while, by contrast, in deep SWI all of these values were 100%. Therefore, one can conclude that 99mTc-HMPAO labelled leucocyte scan permits accurate diagnosis of deep SWI, solving the main clinical problem in this field. In the present study the categorisation of patients without taking into account 99mTc-HMPAO labelled leucocyte planar scan findings caused a non-negligible number of cases of superficial SWI to be treated as though they were deep SWI. This "overestimation" led to unnecessary surgery, increased and prolonged use of antibiotics with more (higher) toxicity and additional expense.

Aged↗
PubMed2000

Transcript imaging of the development of human T helper cells using oligonucleotide arrays.

Many pathological processes, including those causing allergies and autoimmune diseases, are associated with the presence of specialized subsets of T helper cells at the site of inflammation. Understanding the genetic program that controls the functional properties of T helper type 1 (Th1) versus T helper type 2 (Th2) cells may provide insight into the pathophysiology of inflammatory diseases. We compared the gene-expression profiles of human Th1 and Th2 cells using high-density oligonucleotide arrays with the capacity to display transcript levels of 6,000 human genes. Here we analyse the data sets derived from five independent experiments using statistical algorithms. This approach resulted in the identification of 215 differentially expressed genes, encoding proteins involved in transcriptional regulation, apoptosis, proteolysis, and cell adhesion and migration. A subset of these genes was further upregulated by exposure of differentiated Th1 cells to interleukin-12 (IL-12), as confirmed by kinetic PCR analysis, indicating that IL-12 modulates the effector functions of Th1 cells in the absence of antigenic stimulation. Functional assays and in vivo expression of selected genes have validated the biological relevance of our study. Our results provide new insight into the transcriptional program controlling the functional diversity of subsets of T helper cells.

Apoptosis↗
PubMed1999

Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects.

The peroxisome proliferator-activated receptors (PPARs) include three receptor subtypes encoded by separate genes: PPARalpha, PPARdelta, and PPARgamma. PPARgamma has been implicated as a mediator of adipocyte differentiation and the mechanism by which thiazolidinedione drugs exert in vivo insulin sensitization. Here we characterized novel, non-thiazolidinedione agonists for PPARgamma and PPARdelta that were identified by radioligand binding assays. In transient transactivation assays these ligands were agonists of the receptors to which they bind. Protease protection studies showed that ligand binding produced specific alterations in receptor conformation. Both PPARgamma and PPARdelta directly interacted with a nuclear receptor co-activator (CREB-binding protein) in an agonist-dependent manner. Only the PPARgamma agonists were able to promote differentiation of 3T3-L1 preadipocytes. In diabetic db/db mice all PPARgamma agonists were orally active insulin-sensitizing agents producing reductions of elevated plasma glucose and triglyceride concentrations. In contrast, selective in vivo activation of PPARdelta did not significantly affect these parameters. In vivo PPARalpha activation with WY-14653 resulted in reductions in elevated triglyceride levels with minimal effect on hyperglycemia. We conclude that: 1) synthetic non-thiazolidinediones can serve as ligands of PPARgamma and PPARdelta; 2) ligand-dependent activation of PPARdelta involves an apparent conformational change and association of the receptor ligand binding domain with CREB-binding protein; 3) PPARgamma activation (but not PPARdelta or PPARalpha activation) is sufficient to potentiate preadipocyte differentiation; 4) non-thiazolidinedione PPARgamma agonists improve hyperglycemia and hypertriglyceridemia in vivo; 5) although PPARalpha activation is sufficient to affect triglyceride metabolism, PPARdelta activation does not appear to modulate glucose or triglyceride levels.

Adipocytes↗
PubMed1999

Preliminary investigation of voice onset time production in persons with dysphagia.

The purpose of this study was to determine whether voice onset time (VOT) values of persons with dysphagia differed from those of a person with normal swallow function. Five male subjects with dysphagia (average age = 80.6 years) and a control subject (age = 79 years) read 18 consonant-vowel-consonant words in quasi-random order. These syllables began with the voiced and voiceless cognates from the three stop places of articulation (i.e., bilabial, alveolar, and velar). These consonants were followed by the vowels /i/, /a/, and /u/. Digital audio tape recordings were performed and speech was digitized onto disk. Measurements were completed using BLISS software (Mertus J: BLISS User's Manual. Providence: Department of Cognitive and Linguistic Sciences, Brown University, 1989) implemented on a 486 microcomputer. Averages and standard deviations of the VOT measures for the six stop consonants were compared between the two experimental groups. For the dysphagic speakers, average VOT values for voiceless stops were shorter, and there were larger negative VOT values for voiced stops. Standard deviations for the VOT productions pf the dysphagic subjects were smaller. Statistical comparisons showed significant differences between individual dysphagic speakers and the normal control for three of the five subjects. These preliminary data suggest that dysphagia affects the fine motor control required for accurate VOT production in speech.

Aged↗
PubMed1999

Treatment with amantadine potentiated motor learning in a patient with traumatic brain injury of 15 years' duration.

This study sought to determine whether pharmacotherapy with amantadine potentiates motor recovery in an 18-year-old man with traumatic brain injury (TBI) of 15 years' duration. This uncontrolled single-case multiple-baseline design allowed preliminary evaluation of amantadine within the context of standard data-collection procedures on the TBI unit. Measurements tracked speed of wheelchair propulsion, wheelchair transfer, donning shirt, and inserting pegs into holes. Data were collected during a 3-week practice period, followed by a 6-week period of practice plus daily treatment with amantadine. The rate at which performance improved was significantly increased with drug treatment in the wheelchair transfer task. There was a statistically insignificant trend toward improvement in donning shirt. Amantadine did not appear to potentiate recovery in the wheelchair propulsion or peg placement tasks. The results suggest that amantadine facilitates some measures of motor recovery in chronic brain injury. Further trials are warranted to investigate this issue.

Adolescent↗
PubMed1999

[Responsibility of the pharmaceutical industry in health safety].

Under this title will be recalled the responsibilities exerted by the Pharmaceutical Industry in two different fields: in the field of drug production, which has to meet the most rigorous constraints in matter of quality (Good Manufacturing Practices, quality assurance...) under supervision of the pharmaceutical structure; in the field of drug use: after the initial evaluation of the benefit/risk ratio, on which in based the drug registration, it is the responsibility of the Industry to contribute constantly to the good use of medicines and to its optimization (information of health professionals, patient information, pharmacovigilance, and if necessary sanitary safety measures...).

Drug Industry↗
PubMed1998

Efficient display of an HCV cDNA expression library as C-terminal fusion to the capsid protein D of bacteriophage lambda.

We describe the construction and characterization of a hepatitis C virus (HCV) cDNA expression library displayed as a fusion to the carboxy terminus of the capsid protein D of bacteriophage lambda. cDNA inserts were obtained by tagged random-priming of the HCV genome and cloned into a lambda vector from which chimeric phage bearing both wild-type D protein and D fusion products on the capsid surface were produced. The resulting library was affinity-selected with anti-HCV human monoclonal antibodies recognizing linear or conformational epitopes, and human sera from HCV-infected patients. Selection was monitored by immuno-screening experiments, ELISA, and sequence analysis of positive clones. The performance of this library was compared with two additional HCV cDNA display libraries generated as N-terminal fusions to the III and VIII capsid proteins of filamentous phage M13. The results obtained demonstrate the great potential of the lambda display system for constructing complex cDNA libraries for natural ligand discovery.

Antibodies, Monoclonal↗
PubMed1998

In vitro susceptibility of Staphylococcus aureus isolated from blood to currently used antistaphylococcal drugs.

Changes in antibiotic susceptibility was evaluated in 77 consecutive nosocomial clinical isolates of Staphylococcus aureus collected from 1986 to 1994 at the Umberto I Polyclinic of the University of Rome (63 isolates) and from 7 other Roman hospitals (14 isolates). Oxacillin resistance in these isolates increased from 39% during the 1980s to 69% during the 1990s. Significant increases in resistance to ciprofloxacin, clindamycin and rifampicin were observed among oxacillin-resistant strains. No resistance to glycopeptides was observed although both teicoplanin and vancomycin had slightly reduced antistaphylococcal activity.

Anti-Bacterial Agents↗
PubMed1998

In vivo detection of coronary artery anomalies in asymptomatic athletes by echocardiographic screening.

BACKGROUND: Anomalous origin of coronary arteries (AOCA) is a rare congenital disease. Although it may have a benign course, it has been identified as a frequent cause of sports-related sudden death. Unfortunately, in vivo detection of AOCA is not easy, as individuals with this anomaly often are asymptomatic and show no signs of myocardial ischemia. Presently, transthoracic two-dimensional echocardiography (TTE) is the only noninvasive, widely available tool to visualize the ostia and first tracts of coronary arteries. OBJECTIVE: To assess the efficacy of TTE in the screening of AOCA in a large athletic population. STUDY DESIGN: In a prospective study, we assessed the ostia and first tracts of coronary arteries in 3,650 subjects (mean age, 30+/-12 years) practicing different sports at various competitive levels. Subjects underwent a TTE examination in our laboratory for scientific or diagnostic purposes. RESULTS: Technically satisfactory echocardiograms were obtained in 3,504 subjects (96%); a clear visualization of the ostia and first tracts of both coronary arteries was obtained in 3,150 cases (90%). Three asymptomatic athletes (0.09%) were suspected to have an AOCA; two with a right coronary artery origin from the left sinus, and one with a left coronary artery origin from the right sinus. Diagnosis was confirmed by coronary angiography. CONCLUSIONS: Our study indicated that AOCA is rare in asymptomatic athletes. Systematic and accurate exploration of coronary anatomy in athletes referred for a diagnostic TTE examination may be useful in identifying those with AOCA.

Adolescent↗
PubMed1998

Clinical usefulness of technetium-99m-HMPAO-labeled leukocyte scan in prosthetic vascular graft infection.

UNLABELLED: The infection of a prosthetic vascular graft (PVGI), although rare, is the most severe complication in reconstructive vascular surgery. The early diagnosis of this complication reduces the death rate from surgery. Aortofemoral graft infections differ clinically from peripheral graft infections in significant ways. The aim of this article is to evaluate separately the reliability of the 99mTc-HMPAO-labeled leukocyte scan or white blood cell count (WBC) in the early detection of both aortofemoral and peripheral graft infections. METHODS: One hundred sixty-two WBCs were performed on 129 consecutive patients with suspected aortofemoral (122 scans) and peripheral (40 scans) graft infection and in a 12-patient control group. Patients with suspected PVGI were categorized into three groups on the basis of their signs and symptoms on readmission: (a) patients with specific signs of graft infection (Group A); (b) patients with nonspecific signs of graft infection (Group B); and (c) patients with anastomotic aneurysms (Group C). Gram's stains of the perigraft exudate and graft cultures were performed and used as the gold standard in patients who underwent surgery. An 18-mo clinical follow-up was done to assess the presence or absence of graft infection in patients who did not have surgery. RESULTS: In patients with suspected aortofemoral graft infections, the overall sensitivity, specificity and accuracy of WBCs (Groups A, B, C) were 100%, 92.5% and 97.5%, respectively, whereas sensitivity, specificity and accuracy calculated in the patients with nonspecific signs of graft infection (Groups B, C) were 100%, 92.3% and 96.9%, respectively. In patients with suspected peripheral graft infections, sensitivity, specificity and accuracy were 100%. CONCLUSION: The white blood cell scan seems a reliable diagnostic method for early diagnosis of PVGI, and it is more useful in aortofemoral graft infections.

Blood Vessel Prosthesis↗
PubMed1997

Identification of a novel type 1 diabetes-specific epitope by screening phage libraries with sera from pre-diabetic patients.

We used random peptide libraries displayed on phage to search for ligands to insulin dependent diabetes mellitus-related antibodies and were able to identify several candidate disease-related peptides. One of them, clone 92, showed a significant difference in the frequency of reactivity with the sera of patients and normal controls. Human immunoglobulins immunopurified on phage 92 specifically stained the islets on human pancreatic sections. When injected into rabbits, the selected peptide elicited antibodies that also stained human and rat pancreatic sections, with a pattern similar to that observed with immunoglobulins purified from the sera of patients. No reactivity was observed in other tissues. Our results indicate that the peptide identified in this work mimics a novel, diabetes-related self-antigen.

Animals↗