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Biomedical subjects

E Ferrari

Publications and source records attributed to E Ferrari.

At least 109 records · Page 6Linked to original sources
PubMed1997

SCH 43478 and analogs: in vitro activity and in vivo efficacy of novel agents for herpesvirus type 2.

SCH 43478 and analogs are a class of non-nucleoside antiviral agents that have potent and selective activity against herpes simplex virus type 2 (HSV-2). The IC50 for these compounds in plaque reduction analysis using Vero cells ranges from 0.8 to 2.0 microg/ml. All compounds have a LC50 > 100 microg/ml in cytotoxicity analysis. Mechanism of action studies suggest that these molecules have an effect on the transactivation of viral immediate early (alpha) gene expression. Time of addition studies indicate that antiviral activity of these analogs is limited to the initial 2-3 h after infection and is not due to inhibition of viral adsorption or penetration. Analysis of HSV protein expression demonstrates that SCH 49286 inhibits the accumulation of viral immediate early (alpha) gene products. SCH 43478 demonstrates statistically significant efficacy (P < 0.05) in the guinea pig genital model of HSV infection. Following subcutaneous administration in a therapeutic treatment regimen, SCH 43478 (90 mg/kg/day) is efficacious in reducing the number and severity of lesions and the neurological complications of acute HSV infection. Thus, SCH 43478 and analogs are anti-herpesvirus agents with a unique mechanism of action.

Adsorption↗
PubMed1997

Indocyanine green angiography in central serous chorioretinopathy. ICG angiography in CSC.

PURPOSE: To analyse images obtained by indocyanine green angiography in central serous chorioretinopathy (CSC). METHODS: Ninety patients affected with CSC were examined using indocyanine green angiography. RESULTS: CSC was detected in 127 of the 180 eyes examined. Leakage points were detected in 99 eyes with fluorescein angiography; in 85 of these eyes, they corresponded to hyperfluorescence with indocyanine green angiography, while a hyperfluorescence of the neuroepithelial detachment was seen in 21 eyes. Areas of choroidal hyperpermeability were seen in all 127 eyes with CSC and in 9 fellow eyes. With ICG angiography, the appearance of pigment epithelial detachments was similar to that previously described (early hyperfluorescence and later hypofluorescence), and was seen in 47 eyes. In 103 eyes, hypofluorescent lesions of various sizes, were detected which became more marked in the later stages. These lesions corresponded to retinal pigment epithelium lesions in fluorescein angiography, mainly hyperfluorescence caused by window defect. We were also able to observe RPE atrophic tracts in 31 eyes. These tracts appeared hyperfluorescent in 11 eyes where a minimal amount of RPE atrophy was present and hypofluorescent in 20 eyes in which the tract had marked RPE atrophy. CONCLUSION: The results obtained confirm the finding of choroidal hyperpermeability and subretinal diffusion of ICG, which indicate involvement of the choroid in CSC. The observation of progressively hypofluorescent lesions corresponding to retinal pigment epithelium alterations suggests that there may be as yet unknown interactions of pigment epithelium and ICG.

Adult↗
PubMed1997

Hyperviscosity and microproteinuria in central obesity: relevance to cardiovascular risk.

OBJECTIVES: To investigate the role of blood rheology changes in the occurrence of glomerular proteinuria in obese patients with central fat distribution. SUBJECTS: Fifty-nine obese out-patients (31 with central and 28 with peripheral body fat distribution) and 24 healthy subjects. MEASUREMENTS: Blood and plasma viscosity (Rotational viscometer CV100 HAAKE), erythrocyte deformability (whole-blood filtration time), fibrinogen (nephelometry), urinary excretion rates of albumin, IgG, transferrin and IgA (nephelometry). RESULTS: Higher blood viscosity (at low and high shear-rates), plasma viscosity, fibrinogen, erythrocyte aggregability and lower erythrocyte deformability were found in patients with central obesity than in patients with peripheral obesity (P < 0.01) and in healthy subjects (P < 0.001). Furthermore an increased urinary excretion rate of albumin (P < 0.001), IgG (P < 0.001), transferrin (P < 0.01) and IgA (P < 0.05) was found in patients with central obesity than in the other two groups. Blood hyperviscosity (at shear-rate 1 s-1 and 1/200 ratio) significantly correlated with the amount of urinary excretion of proteins independently of the other clinical and metabolic variables. CONCLUSIONS: The data demonstrated haemorheologic disorders related to pathologic proteinuria in patients with central obesity. The interaction between these two components may increase the risk of widespread cardiovascular disease.

Adult↗
PubMed1997

Clinical epidemiology of venous thromboembolic disease. Results of a French Multicentre Registry.

OBJECTIVE: Between July 1992 and December 1994, 16 French hospital centres, mainly cardiological, participated in a non-controlled observational study on venous thromboembolic disease. The objective of this survey was to collect data concerning the current status of pulmonary embolism and deep venous thrombosis. PATIENTS: During this period, 547 patients were included: 446 with deep venous thrombosis and 387 with pulmonary embolisms. RESULTS: Mean age of patients was 63 +/- 21 years. There were no significant differences between the sexes. Pulmonary embolism and deep venous thrombosis tended to occur more frequently during the autumn and winter. In 30% of cases, prior deep venous thrombosis or pulmonary embolism was noted. No cause was found for the condition in 47% of cases. Ultrasound (echocardiography and/or venous ultrasound) was the most frequently requested investigation. Intravenous heparin remains the most widely used treatment (76%). Oral anticoagulation was begun before day 3 in less than 31% of cases. Thrombolytic treatment was used in 20% of pulmonary embolism cases, but was rarely prescribed for deep venous thrombosis (2.2%). The hospital recurrence rate (12/547 cases) was fairly low. The search for occult malignancy, performed in 48% of cases, seems to remain one of the major concerns of physicians. The combined pulmonary embolism and deep venous thrombosis mortality rate was 4.4%, while the death rate for pulmonary embolism alone was 6.2%.

Adult↗
PubMed1997

SCH 48973: a potent, broad-spectrum, antienterovirus compound.

SCH 48973 is a novel molecule with potent, selective, antienterovirus activity. In assays of the cytopathic effect against five picornaviruses, SCH 48973 had antiviral activity (50% inhibitory concentrations [IC50s]) of 0.02 to 0.11 microg/ml, with no detectable cytotoxicity at 50 microg/ml. SCH 48973 inhibited 80% of 154 recent human enterovirus isolates at an IC50 of 0.9 microg/ml. The antiviral activity of SCH 48973 is derived from its specific interaction with viral capsid, as confirmed by competition binding studies. The affinity constant (Ki) for SCH 48973 binding to poliovirus was 8.85 x 10(-8) M. In kinetic studies, a maximum of approximately 44 molecules of SCH 48973 were bound to poliovirus capsid. SCH 48973 demonstrated efficacy in a murine poliovirus model of enterovirus disease. SCH 48973 increased the survival of infected mice when it was administered orally at dosages of 3 to 20 mg/kg of body weight/day. Oral administration of SCH 48973 also reduced viral titers in the brains of infected mice. On the basis of its in vitro and in vivo profiles, SCH 48973 represents a potential candidate for therapeutic intervention against enterovirus infections.

Animals↗
PubMed1997

The ECG in pulmonary embolism. Predictive value of negative T waves in precordial leads--80 case reports.

BACKGROUND AND STUDY OBJECTIVE: The value of the ECG for the diagnosis of pulmonary embolism (PE) is debatable. Once the diagnosis of PE has been established, however, the ECG could allow the massive forms to be distinguished. The purpose of our study was to analyze the ECG signs in patients hospitalized for PE in a cardiology unit. DESIGN: Taking a series of 80 consecutive patients hospitalized for PE, we analyzed the ECGs on admission and then during hospitalization. We sought to evaluate changes in ECG signs compared with angiographic and hemodynamic changes in PE. RESULTS: T-wave inversion in the precordial leads is the most common abnormality (68%), and represents the ECG sign best correlated to the severity of the PE. Among those patients with anterior T-wave inversion, 90% had a Miller index over 50% (mean, 60 +/- 8%). Eighty-one percent had a mean pulmonary arterial pressure (PAP) over 30 mm Hg (mean, 37 +/- 8%). This subepicardial ischemic pattern is an even stronger marker of severity when it appears as early as the first day (p < 0.01). Its reversibility is correlated to the changes in PE. After thrombolysis in particular, normalization of repolarization systematically indicates mean Miller and PAP indexes of < 20% and < 20 mm Hg, respectively. CONCLUSIONS: The anterior subepicardial ischemic pattern is the most frequent ECG sign of massive PE. This parameter is easy to obtain and reflects the severity of PE. Its reversibility before the sixth day points to a good outcome or high level of therapeutic efficacy.

Adult↗
PubMed1997

Generation of large libraries of random mutants in Bacillus subtilis by PCR-based plasmid multimerization.

We describe a PCR-based method for the generation of plasmid multimers that can be directly transformed into Bacillus subtilis with very high efficiency. This technique is particularly useful for the generation of large libraries of randomly mutagenized genes, which are required for the optimization of enzymes by directed evolution. We subjected the gene coding for the protease subtilisin to six consecutive rounds of PCR at three different levels of mutagenicity. The resulting 18 populations were cloned using our PCR multimerization protocol, and the mutation frequencies were determined by DNA sequencing. The resulting data demonstrate that the mutation frequency during PCR can be controlled by adding varying concentrations of manganese chloride to the reaction mixture. We observed a bias in the type of base pair changes with A and T being mutated much more frequently than C and G. We determined the fraction of active clones in all populations and found that its natural logarithm is proportional to the average mutation frequency of the populations. These data reveal that a fraction of about 0.27 of all possible mutations leads to the inactivation of the subtilisin gene, which provides a measure for its structural plasticity.

Bacillus subtilis↗
PubMed1997

Changes in endocrine circadian rhythms as markers of physiological and pathological brain aging.

We studied the circadian rhythm of plasma melatonin, growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), and cortisol in 52 mentally healthy old subjects, 35 old demented patients, and 22 clinically healthy young controls. When compared to young controls, the circadian profile of plasma melatonin of old subjects, both demented or not, was clearly flattened, particularly during the night. The selective impairment of nocturnal melatonin secretion was significantly related to both the age and the severity of mental impairment (Mini Mental State Examination [MMSE] score). The PRL and GH circadian profiles were similar in the three groups during the day, but a significant lowering of the values recorded during the night occurred with aging. The impairment of the nocturnal secretion was related to the subjects' age and, for the GH secretory pattern only, also to the MMSE score. The ACTH circadian profile was similar in the three groups studied, even when old subjects exhibited higher ACTH levels throughout the 24 h cycle, compared to young controls. Significantly higher cortisol values at evening- and nighttime occurred in elderly subjects and particularly in the demented group. Both the mean levels and the nadir values of plasma cortisol were positively related to age and negatively to MMSE score. In order to verify the sensitivity of the hypothalamo-pituitary-adrenal (HPA) axis to the steroid feedback, the circadian profile of plasma cortisol was evaluated also after dexamethasone (DXM) administration (1 mg at 23:00 h); the sensitivity of the HPA axis was significantly impaired in old subjects and particularly in the demented ones. These findings suggest that the neuroendocrine alterations already present in physiological aging, due to both anatomical damages and unbalanced central neurotransmitters, are enhanced in senile dementia.

Adrenocorticotropic Hormone↗
PubMed1997

Nephelometry in the clinical assessment of glomerular proteinuria and tubular function in diabetic nephropathy.

Urinary excretion rate and total clearances of albumin, IgG, IgA and alpha 1-microglobulin, together with selectivity index and proteinuria, were determined by computerized nephelometry in 187 IDDM and NIDDM diabetic out-patients and in 39 healthy subjects in order to perform a prompt clinical assessment of diabetic nephropathy. Significant correlations between nephelometric and RIA procedures were demonstrated for the urinary excretion of albumin (p < 0.001) and total IgG (p < 0.001) in diabetic patients and healthy subjects. Nephelometry allowed us to classify diabetic patients in different stages of nephropathy: non nephropathic, normoalbuminuric with hyperfiltration, with incipient (microalbuminuric) and overt nephropathy (macroalbuminuric). Thirty consecutive subjects were analyzed within 1 h from the beginning of the procedure. A normal tubular function was demonstrated in non nephropathic, hyperfiltering and in 34% of microalbuminuric diabetic patients. On the contrary, in 66% of microalbuminuric and in 93% of macroalbuminuric patients alpha 1-microglobulin urinary levels were found above the upper normal limit. Urinary excretion of IgA was significantly increased only in macroalbuminuric diabetic patients (p < 0.001); this marker might therefore characterise the stage of overt nephropathy. Computerized nephelometry can be considered as a prompt, reproducible and high sensitive approach in the clinical evaluation of proteinuria and tubular function in diabetic renal disease.

Adult↗
PubMed1996

Immunoendocrine aspects of anorexia nervosa.

The T-lymphocyte proliferative response to phytohemoagglutinin (PHA) stimulation was the same in 11 anorexic women, 6 restricted (AN-R) and 5 bulimic (AN-B), and in 11 sex- and age-matched controls, in basal conditions and after acute administration of corticotropin-releasing hormone (CRH). Basal plasma levels of ACTH and cortisol were higher in patients than in controls, while beta-endorphin (beta-EP), growth hormone (GH) and prolactin (PRL) concentrations did not differ in the two groups. ACTH and beta-EP responses to CRH stimulation were blunted in patients, while those of cortisol did not differ in the two groups. ACTH, beta-EP and cortisol responses to the dexamethasone suppression test were impaired in 55% of the patients. Baseline T-lymphocyte concentrations of cholecystokinin-8 (CCK-8) and beta-EP were measured in another group of 56 anorexics, 33 restricted and 23 bulimic, and in 24 controls. CCK-8 values were significantly lower and beta-EP values significantly higher in patients than in controls.

Adolescent↗
PubMed1996

A functional Spo0A is required for maximal aprE expression in Bacillus subtilis.

The initiation of sporulation in Bacillus subtilis is under control of the transcriptional factor Spo0A. Most Spo0A mutants fail to initiate the sporulation process and all the sporulation initiated processes such as the synthesis of subtilisin. However, the product of spo0A9V, one of the several spo0A mutants characterized, distinguishes itself in the fact that, while it appears to effectively repress abrB, it fails to activate the spoIIA operon. The aim of this study was to examine the effect of the spo0A9V mutation on aprE expression and we found that in different genetic backgrounds, the spo0A9V mutation has a negative effect on aprE::lacZ expression.

Bacillus subtilis↗
PubMed1996

Chrono-neuroendocrine markers of the aging brain.

The study of the neuroendocrine changes occurring in aging may give information about the CNS functions, and also explain the impaired plasticity of the aged organism. In 16 elderly women and in 14 young controls, the circadian rhythms of plasma melatonin, GH, PRL, ACTH and cortisol, and of oral temperature were simultaneously studied. The plasma cortisol circadian rhythm was also evaluated after DXM administration (1 mg orally at 23:00). The circadian profile of all the bioperiodic functions evaluated was clearly flattened in elderly subjects, and an impairment of the hormonal nocturnal secretion of GH, PRL and melatonin was apparent in elderly subjects when compared to young controls. The plasma ACTH levels throughout the 24-hour cycle were significantly higher in elderly than in young subjects. The cortisol circadian profile exhibited significantly higher values in the evening- and night-time in elderly subjects, compared to young controls; the cortisol nadir values were significantly age-related. A reduction of the sensitivity to DXM inhibition occurred in the elderly group. Both the selective impairment of nocturnal melatonin secretion, and the reduction of hypothalamo-pituitary-adrenal (HPA) sensitivity to steroid feed-back might be considered as markers of aging brain. The neuroendocrine alterations of physiological aging may be ascribable to both the structural and neurochemical changes occurring in the CNS.

Adrenocorticotropic Hormone↗
PubMed1996

Antipicornavirus activity of SCH 47802 and analogs: in vitro and in vivo studies.

SCH 47802 and its derivatives are potent inhibitors of enteroviruses in vitro. The IC50 for SCH 47802 ranges from 0.03 to 10 micrograms/ml when tested against a spectrum of enteroviruses in plaque reduction assays. The compounds have in vitro therapeutic indices of at least 81 based on viral cytopathic effect (CPE) assays. The in vitro activity of SCH 47802 translates into in vivo activity in the murine model of poliovirus encephalitis. In an oral dosing regimen, SCH 47802 protects mice from mortality at 60 mg/kg per day. Consistent with the in vivo efficacy, pharmacokinetic analyses after oral dosing with SCH 47802 demonstrate serum levels of the compound above the in vitro IC50 for poliovirus for at least 4 h. SCH 47802 and its active analogs stabilize poliovirus to thermal inactivation indicating that the compounds bind to the virus capsid. Mechanistic studies with poliovirus indicate that SCH 47802 acts early in viral infection. This series of molecules represents potential candidates for the treatment of human enterovirus infections.

Animals↗
PubMed1996

Aspiration needle biopsy refines preoperative diagnosis of thyroid nodules defined at fine needle aspiration as microfollicular nodule.

The aim of this paper was to verify the hypothesis that large needle biopsy performed preoperatively can refine preoperative fine needle aspiration (FNA) cytological diagnoses of microfollicular nodules. Since 1980 we have been using FNA and aspiration needle biopsy (ANB) (18 or 16 gauge needles) to select for surgery all euthyroid patients with palpable thyroid nodules referred to our department. From 1980 to 1994, 6,124 patients (12% male, 88% female) with thyroid nodules (71% single, 29% multiple) were examined by FNA; 29% of these patients were also examined preoperatively by ANB histology. Of all the nodule patients examined, 371 received a preoperative FNA diagnosis of microfollicular nodule. Two hundred and fifty-four of these nodules (68%) were also examined preoperatively by ANB. Unsatisfactory ANB specimens constituted 17% of cases; pure microfollicular structure was confirmed by ANB in 36% of the nodules; ANB showed the remaining 47% to contain a macrofollicular component, thus suggesting a benign hyperplastic lesion. Twelve nodules which were found to be microfollicular at FNA cytology and micro-macrofollicular at ANB were excised and were subsequently determined as benign at definitive postoperative histology. These data indicate the utility of ANB in refining the preoperative FNA diagnosis of microfollicular nodule and in preoperatively identifying benign hyperplastic mixed micro-macrofollicular lesions which can be followed by observation.

Adult↗
PubMed1996

The ampS-nprE (124 degrees-127 degrees) region of the Bacillus subtilis 168 chromosome: sequencing of a 27 kb segment and identification of several genes in the area.

A stretch of DNA approximately 27 kb in length, adjacent to the nprE gene of Bacillus subtilis, has been sequenced. The sequenced fragment carries a total of 23 ORFs. Of these, 15 could be assigned probable functions based on homologies to characterized genes either in B. subtilis or in other organisms. The sequencing of this region has also allowed us to assign to this area adeC and strB, previously located on the other side of nprE, between nprE and the pyr operon.

Bacillus subtilis↗
PubMed1996

Enzymatic characterization of hepatitis C virus NS3/4A complexes expressed in mammalian cells by using the herpes simplex virus amplicon system.

The hepatitis C virus (HCV) NS3 protein possesses three enzymatic activities: an N-terminal serine protease activity, a C-terminal RNA-stimulated NTPase activity, and an RNA helicase activity. To characterize them, the full-length NS3(631)/4A and three C-terminal truncated proteases (NS3(201)/4A, NS3(181)/4A, and NS3(155)/4A were expressed in mammalian cells with HSV amplicon-defective viruses. Our results revealed that all of the NS3/4A proteins produced in mammalian cells (except NS3(155)/4A) are active in processing both cis and trans cleavage sites. Temperature optimization studies revealed that the protease is more active at temperatures ranging from 4 to 25 degrees C and is completely inactive at 42 degrees C. The RNA-stimulated ATPase activity was characterized with a partially purified NS3(631)/4A fraction and has a higher optimal temperature at 37 to 42 degrees C. The effects of detergents on both NS3 protease and RNA-stimulated ATPase were similar. Nonionic detergents such as Triton X-100, Nonidet P-40 and Tween 20 did not affect the activities, while anionic detergents such as sodium dodecyl sulfate and deoxycholic acid were inhibitory. Zwitterionic detergent such as 3-[(3-cholamidopropyl)- dimethyl-ammoniol-1-propanesulfonate (CHAPS) inhibited protease activity at a concentration of 0.5% (8 mM), which had no effect on ATPase activity. Finally, RNA-unwinding activity was demonstrated in the NS3(631)/4A fraction but not in the similarly purified NS3(181)/4A and NS3(201)/4A fractions. NS(363)/4A unwinds RNA duplexes with 3' but not 5' single-stranded overhangs, suggesting that the NS3 RNA helicase functions in a 3'-to-5' direction.

Adenosine Triphosphatases↗
PubMed1996

Needle aspiration techniques in preoperative selection of patients with thyroid nodules: a long-term study.

PURPOSE: Long-term evaluation of the combination of two needle aspiration techniques (NAT) (fine-needle aspiration [FNA] and aspiration needle biopsy [ANB]) in performing an efficient preoperative selection of palpable thyroid nodules. PATIENTS AND METHODS: Eight years of extensive use of surgery for the detection of thyroid cancer was compared with 12 years of preoperative selection of by NAT. RESULTS: A total of 1,140 operations were performed from 1972 to 1979, and 35 malignant nodules were discovered (3.1%). Five thousand four hundred three patients were examined by NAT from 1980 to 1992; 483 (9%) underwent surgery and 158 malignant nodules were excised. The number of malignant nodules identified by NAT was 166 (eight were not excised) (3.1% of the total population examined). The principal clinical and pathologic features were similar in both groups. ANB yielded a definite benign diagnosis in 88 patients with inadequate FNA findings, it correctly identified four malignant nodules diagnosed as benign by FNA, it showed a macrofollicular component in 115 nodules diagnosed by FNA as microfollicular nodules, and it significantly changed the predictive value of 79 suspicions FNA diagnoses. CONCLUSION: Introduction of NAT reduced the number of operations for palpable thyroid nodules from 143 to 40 per year and increased from four to 13 the number of malignant nodules excised without any change in the overall incidence of malignant nodules. The combination of ANB to FNA significantly contributed to the high and efficient preoperative patient selection, principally by reducing the number of indeterminate or suspicious, as well as false-negative, preoperative FNA diagnoses.

Adolescent↗