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Biomedical subjects

F Marini

Publications and source records attributed to F Marini.

At least 19 recordsLinked to original sources
PubMed2006

Modeling cross correlations within a many-assets market.

A simple model for simulating cross correlations of a many-assets market is discussed. Correlations between assets are initially considered within the context of the well-known one-factor model, in which a driving term common to all stocks is present. The results are compared to those of real market data corresponding to a set of 445 stocks taken from the Standard and Poors 500 index. The model is further extended by introducing a stochastic volatility within each time series using an autoregressive scheme. This artificial market reproduces the empirically observed fat tails in the distribution function of logarithmic price variations and, more important, leads to additional cross correlations between the time series, in better agreement with the real market behavior.

Journal Article↗
PubMed2006

MEN1 family with a novel frameshift mutation.

Multiple endocrine neoplasm type 1 (MEN1) syndrome predisposes to the development of endocrine and non-endocrine tumors with an autosomal dominant pattern of inheritance. Different mutations have been found throughout the gene with a variable phenotype expression. The proband, a Caucasian man, was admitted to our department in 2001, at the age of 51 because of a 1-yr history of diarrhoea and hypertension. He reported a previous intestinal resection for bowel occlusion with a histological diagnosis of unspecified mesenchymal neoplasia. He had also undergone a left adrenalectomy for a large nonfunctioning adrenal adenoma. Subsequently, he had suffered from gastralgia and melena; a gastroduodenoscopy showed an erosive gastritis. His family history was negative for endocrine disorders. On physical examination, multiple abdominal cutaneous lipomas and facial angiofibromas were observed. Biochemical screening revealed a primary hyperparathyroidism and an increase in circulating levels of PRL, chromogranin-A, gastrin and glucagon. The whole body computed tomography (CT) scan, the 111In-octreotide scan and the pituitary magnetic resonance imaging (MRI) did not reveal any abnormality. The presence of small neuroendocrine tumors was suspected by a positron emission tomography uptake in the epigastric region. The endoscopic ultrasound revealed a pancreatic lesion sized 1.1 cm that is under evaluation. Direct DNA sequencing analysis of the proband MEN1 gene revealed the 579delG frameshift mutation in the exon 3. The genetic screening of the family revealed the same mutation in 3 out of 5 offspring. The biochemical screening revealed some features of the MEN1 syndrome in all three of them. In conclusion, a novel frameshift MEN1 mutation was found in kindred with an apparently negative family history. Our experience confirms that MEN1 syndrome is a complex and underestimated condition, unless specifically investigated by trained specialists.

Adult↗
PubMed2005

Genetics and pharmacogenetics of osteoporosis.

Osteoporosis is a skeletal chronic multifactorial disease characterised by abnormal low bone mass and microarchitectural deterioration of bone tissue. This disorder, present in both sexes, related to environmental and genetic factors, is becoming a major public health problem in developed countries. It has a polygenic pattern of inheritance that complicates identification of disease genes [cytokines, calciotropic hormones, sex hormones pathway synthesis and their receptors, bone matrix proteins synthesis genes involved on estrogenic metabolism (CYP19) and LDL receptor-related protein 5 (LRP5) gene]. It is possible to identify associations between candidate genes polymorphisms and disease phenotype in population-based and case-control studies. This could give us promising data for earlier identification of osteoporosis susceptibility and fracture risk. Preventive therapy could be targeted to patients at risk of osteoporosis before fractures occur. Genetic polymorphisms are also starting to be used to predict drug response. A new era of pharmacogenetics represents an interesting prospective to identify the potential individuals to receive customised treatments.

Animals↗
PubMed2004

The Metabolic Syndrome is an independent predictor of cardiovascular disease in Type 2 diabetic subjects. Prospective data from the Verona Diabetes Complications Study.

AIMS: To evaluate the cardiovascular risk associated with the presence of the Metabolic Syndrome in Type 2 diabetic subjects. METHODS: Subjects with the Metabolic Syndrome, defined by WHO criteria, were identified in a large sample of non-insulin-treated Type 2 diabetic patients examined within the Verona Diabetes Complications Study (n = 946). At baseline and after a mean of 4.5 years follow-up, cardiovascular disease (CVD) was assessed by medical history, physical examination, electrocardiogram (ECG) and echo-duplex of carotid and lower limb arteries. Death certificates and medical records of subjects who died during the follow-up were scrutinized in order to identify CVD deaths. In statistical analyses, CVD was considered as an aggregate end-point, including fatal and non-fatal coronary, cerebrovascular and peripheral vascular disease as well as ischaemic ECG abnormalities and vascular lesions at the echo-duplex. RESULTS: The proportion of subjects with the Metabolic Syndrome was very high (92.3%). At the baseline, 31.7% of subjects were coded positive for CVD, which was more prevalent in subjects with the Metabolic Syndrome (32.9 vs. 17.8%, P = 0.005). Among subjects free of CVD at the baseline (n = 559), CVD events during the follow-up were significantly increased in patients with the Metabolic Syndrome as compared with those without it (19.9% vs. 3.9%, P < 0.001). Multiple logistic regression analysis showed that, along with sex, age, smoking and HbA1c, the presence of the Metabolic Syndrome independently predicted prevalent (OR 2.01, P = 0.045) and incident CVD (OR 4.89, P = 0.031). CONCLUSIONS: In Type 2 diabetes, the presence of the Metabolic Syndrome is associated with an almost 5-fold increase in CVD risk.

Aged↗
PubMed2004

Comparison of the efficiency of transduction of leukemic cells by fiber-modified adenoviruses.

Efficient gene transfer with adenoviral type 5 (Ad5) vectors depends on the initial attachment of their fiber, which binds the coxsackie-adenovirus receptor (CAR), and their subsequent internalization, mediated by the interaction of viral penton base with target cell alphav integrins. We previously demonstrated that human leukemic cells lack these receptors and are therefore resistant to Ad5 transduction, limiting efforts to genetically modify these cells. Human leukemic blasts are, however, susceptible to transduction with an adenovector made CAR independent by substitution of a chimeric Ad5/35 fiber [Yotnda et al. (2001). Gene Ther. 8, 930-937]. Other receptors can also be targeted with recombinant ligand moieties incorporated into adenovirus fiber. We have determined which of these fiber-modified adenovectors is most effective at modifying human primary leukemia cells, and lines. We used a replication-incompetent Ad5-beta-gal vector, in which the Ad5 fiber was replaced with fiber from various adenovirus serotypes (Ad35 and Ad11), or modified either with variable length polylysine (K4, K7, K21) or RGD-4C peptide. All the modified fiber vectors transduced primary leukemia cells and cell lines more efficiently than Ad5. Polylysine-substituted Ad5F/K21 and peptide-modified Ad5F/RGD vectors were most effective overall (up to 100% efficiency), whereas Ad5F/RGD was the most effective at transducing B cell acute lymphoblastic leukemia cells (90% efficiency). Ad5F/K21 and Ad5F/RGD should be of value for the genetic modification of human primary leukemia cells.

Adenoviridae↗
PubMed2002

Sevoflurane low-flow anaesthesia: best strategy to reduce Compound A concentration.

BACKGROUND: To define the best strategy to reduce Compound A production in Sevoflurane low-flow anaesthesia by experiments in vitro and in vivo of different absorbers and different anaesthesia machines. METHODS: In vitro Compound A has been measured at 45 degrees C in vitro following Sevoflurane interactions with potassium hydroxide, sodium hydroxide, soda lime, Dragersorb 800 Plus and Amsorb, a new absorber that does not contain sodium or potassium hydroxide. In vivo Compound A concentration in the anaesthesia circuit (inspiratory branch) has been measured using an indirect sampling method through absorber vials (SKC) with active coal granules, during low flows (500 ml/min) general anaesthesia using soda lime, Dragersorb 800 Plus or Amsorb as absorber. Compound A was also measured during low flows (500 ml/min) general anaesthesia using as carbon dioxide absorber soda lime with different anaesthesia machines. RESULTS: In vitro at 45 degrees C Compound A concentration with soda lime and Dragersorb 800 Plus was about 10 times higher than with Amsorb. In vivo the Compound A concentrations in the inspiratory branch of the circuit were lower in the group with Amsorb. CONCLUSION: The Compound A production is minimal with Amsorb as carbon dioxide absorber.

Absorption↗
PubMed2002

Predictors of insulin sensitivity in Type 2 diabetes mellitus.

AIMS: To identify the independent predictors of insulin sensitivity in Type 2 diabetes, and to establish whether isolated Type 2 diabetes (i.e. diabetes without overweight, dyslipidaemia and hypertension) is a condition of insulin resistance. METHODS: We examined 45 patients with non-insulin-treated Type 2 diabetes undergoing a 4-h euglycaemic hyperinsulinaemic clamp (20 mU/m2 per min) combined with 3H-3-D-glucose and 14C-U-glucose infusions and indirect calorimetry. We also examined 1366 patients with non-insulin-treated Type 2 diabetes randomly selected among those attending the Diabetes Clinic and in whom insulin resistance was estimated by Homeostasis Model Assessment (HOMA-IR). RESULTS: In the 45 patients undergoing glucose clamp studies, insulin-mediated total glucose disposal (TGD) was independently and negatively associated with systolic blood pressure (standardized beta coefficient = -0.407, P = 0.003), plasma triglycerides (beta= -0.355, P = 0.007), and HbA1c (beta= -0.350, P = 0.008). The overall variability of TGD explained by these variables was 53%. Overweight diabetic subjects with central fat distribution, hypertension, hypertriglyceridaemia and poor glycometabolic control had insulin-mediated TGD values markedly lower than their lean counterparts without hypertension, with normal triglycerides, and with good glycometabolic control (16 +/- 5 vs. 31 +/- 10 micromol/min per kg lean body mass, P < 0.01). Nevertheless, the latter still were markedly insulin-resistant when compared with sex- and age-matched non-diabetic control subjects (31 +/- 10 vs. 54 +/- 13 micromol/min per kg lean body mass, P < 0.01). In the 1366 Type 2 diabetic patients of the epidemiological study, HOMA-IR value was independently associated with HbA1c (beta = 0.283, P < 0.0001), plasma triglycerides (beta = 0.246, P < 0.0001), body mass index (beta = 0.139, P < 0.001), waist girth (beta = 0.124, P < 0.001) and hypertension (beta = 0.066, P = 0.006). CONCLUSION: Overweight, central fat distribution, dyslipidaemia, hypertension and poor glycometabolic control are strong independent predictors of insulin resistance in Type 2 diabetes. However, reduced insulin sensitivity can be found even when Type 2 diabetes is isolated and well controlled.

Adult↗
PubMed2002

[The vision of welders in France].

PURPOSE: A study was conducted to measure the impact of welding on the vision of welders. METHODOLOGY: This study was conducted in France by the occupational medicine staff of large companies on 1.131 people, namely 850 welders and 281 control subjects. This investigation included two examinations at the beginning and the end of a year. The investigative procedure examined the different welding processes, the percentage of working time spent on welding activity, the length of exposure in years, as well as the medical variables: the optical correction type and history of ocular traumatology. The Visiotest or the Ergovision were used for the visual examination, equipment in common use by occupational medicine departments. RESULTS: The welders were comparatively young (59.53% of them were less than 45 years old). Moreover, for 69.75% of the welders, more than 75% of their activity was devoted to welding. All currently used welding processes were represented, including the modern PLASMA-TIG welding process. No excessive blood alcohol levels were observed in all subjects, but welders did smoke slightly more than the control subjects (40% vs 33%). Self-medication was rather less frequent among the welders, except as regards the use of eye drops, where the proportions were clearly inverted. Optical correction for hyperopia was similar between the two groups; however, as regards myopia, the welders were corrected less often. Lastly, contact lens use was exceptional among the welders. Nearsightedness varied logically with age, but also, inexplicably, with the welding processes. Vision recovery time after exposure to glare was much longer among the welders, except for the PLASMA-TIG processes. No difference was observed in the other parameters of the study. No change in the visual functions studied was noted between the two examinations. DISCUSSION: The examination techniques used showed no impairment of the studied visual functions, probably because companies use protective and preventive eye care methods. Moreover this study is the first to examine the type of welding used by workers and particularly the modern PLASMA-TIG process. The vision recovery time after exposure to glare seems better for the PLASMA-TIG process may be the result of the lower luminous intensity of this process. CONCLUSION: This study was conducted for preventive purposes to contribute to better monitoring of safety and comfort for welding workers and has shown no alteration of the visual function among welders in general.

Adaptation, Ocular↗
PubMed2002

Informing patients about risks and complications of anaesthesia.

BACKGROUND: This study examines the quality of patients' informed consent in patients undergoing minor surgical procedure. Information provided on risks and complications inherent in anaesthesia-care and patients' awareness of specific risks involved in anaesthesia were recorded, and the influence of a questionnaire-form was evaluated. METHODS: This is a prospective controlled study. In the first part (Group I: n=71) social and demographic data, complications and risks communicated to the patient in the preanaesthetic evaluation, as well as patients' satisfaction with the information obtained, were noted. In the second part of the study (Group II: n=201) patients were also asked to answer a questionnaire form concerning their own state of health and their knowledge of risks in anaesthesia. The statistical analysis was conducted using Pearson's Chi square test or t test, and by fitting suitable logistic models. RESULTS: The frequency of the communication of at least one of the risks and complications of anaesthesia has been 43.7% in GI and 59,7% in GII, p=0.019. Patients in class ASA III were informed more (77%, c.i. 59-90) as compared to those in class ASA I-II (52%, c.i. 45-59) (p=0.008); 37% in class ASA I-II and 65% in class ASA III desire the presence of one of their relatives during the preassessment (p=0.016). CONCLUSIONS: Our results indicate that most patients are glad to be informed, even if they are unaware of the risks and complications of anaesthesia. The questionnaire form seems to be an important tool for patient education. Ethical questions are proposed.

Anesthesia↗
PubMed2001

A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia.

The hematopoietic stem cell underlying acute myeloid leukemia (AML) is controversial. Flow cytometry and the DNA-binding dye Hoechst 33342 were previously used to identify a distinct subset of murine hematopoietic stem cells, termed the side population (SP), which rapidly expels Hoechst dye and can reconstitute the bone marrow of lethally irradiated mice. Here, the prevalence and pathogenic role of SP cells in human AML were investigated. Such cells were found in the bone marrow of more than 80% of 61 patients and had a predominant CD34(low/-) immunophenotype. Importantly, they carried cytogenetic markers of AML in all 11 cases of active disease examined and in 2 out of 5 cases in complete hematological remission. Comparison of daunorubicin and mitoxantrone fluorescence emission profiles revealed significantly higher drug efflux from leukemic SP cells than from non-SP cells. Three of 28 SP cell transplants generated overt AML-like disease in nonobese diabetic--severe combined immunodeficient mice. Low but persistent numbers of leukemic SP cells were detected by molecular and immunological assays in half of the remaining mice. Taken together, these findings indicate that SP cells are frequently involved in human AML and may be a target for leukemic transformation. They also suggest a mechanism by which SP cells could escape the effects of cytostatic drugs and might eventually contribute to leukemia relapse. (Blood. 2001;98:1166-1173)

Acute Disease↗
PubMed2001

Autologous antileukemic immune response induced by chronic lymphocytic leukemia B cells expressing the CD40 ligand and interleukin 2 transgenes.

Although the B cells of chronic lymphocytic leukemia (B-CLL cells) express both tumor-specific peptides and major histocompatibility complex (MHC) class I antigens, they lack the capacity for costimulatory signaling, contributing to their protection against host antitumor immunity. To stimulate CLL-specific immune responses, we sought to transfer the human CD40 ligand (hCD40L) gene to B-CLL cells, using an adenoviral vector, in order to upregulate costimulating factors on these cells. Because efficient gene transduction with adenoviral vectors requires the expression of virus receptors on target cells, including the coxsackievirus B-adenovirus receptors (CAR) and alpha(v) integrins, we cocultured B-CLL cells with human embryonic lung fibroblasts (MRC-5 line). This exposure led to increased expression of integrin alpha(v)beta3 on B-CLL cells, which correlated with higher transduction rates. Using this novel prestimulation system, we transduced B-CLL cells with the hCD40L gene. The Ad-hCD40L-infected cells had higher expression of B7 molecules and induced activation of autologous T cells in vitro, but these T cells could not recognize parental leukemic cells. By contrast, an admixture of Ad-hCD40L-positive cells and leukemic cells transduced with the human interleukin 2 (IL-2) gene produced greater T cell activation than did either immunostimulator population alone. Importantly, this combination generated autologous T cells capable of specifically recognizing parental B-CLL cells. These findings suggest that the combined use of genetically modified CD40L-expressing B-CLL cells in combination with IL-2-expressing B-CLL cells may induce therapeutically significant leukemia-specific immune responses.

Adenoviridae↗
PubMed2001

[Sevoflurane in stop-flow interventions. Hemodynamics study].

BACKGROUND: The so called stop-flow operation is based on locoregional perfusion with an antiblastic hypoxic solution of the region invaded by malignant tissue. Cardiocirculatory complications are common, mainly consisting of reduction of cardiac index, increase of arterial pulmonary pressure, systemic vascular resistance and heart rate. Sevoflurane has been used for its stable hemodynamic profile to reduce cardiocirculatory troubles. METHODS: Six patients were submitted to stop-flow operation. General anaesthesia was performed with Sevoflurane 1 MAC in Air/O2. The following parameters were recorded: nitroglycerin infusion m order to maintain the position of the balloon of the catheters, arterial oxygen saturation, end-tidal carbon dioxide, mean arterial pressure, central venous pressure, arterial pulmonary pressure, heart rate and mixed oxygen venous saturation; recordings were performed before stop-flow (T1), during stop-flow (T2) and 10' after reperfusion (T3). RESULTS: Before stop-flow (T1) all the parameters were normal. At T2 heart rate, cardiac index and pulmonary capillary wedge pressure increased whilst mean arterial pressure, systemic vascular resistance and pulmonary vascular resistance decreased. Ten minutes after the end of perfusion (T3) absence of variations in systemic vascular resistance, in pulmonary vascular resistance, in pulmonary capillary wedge pressure, in cardiac index and in mixed oxygen venous saturation were noticed. Heart rate and central venous pressure showed a tendency to decrease. CONCLUSIONS: The hemodynamic profile during stop-flow appears to be stable with general anaesthesia with Sevoflurane.

Aged↗
PubMed2000

Disruption of the developmentally regulated Rev3l gene causes embryonic lethality.

The REV3 gene encodes the catalytic subunit of DNA polymerase (pol) zeta, which can replicate past certain types of DNA lesions [1]. Saccharomyces cerevisiae rev3 mutants are viable and have lower rates of spontaneous and DNA-damage-induced mutagenesis [2]. Reduction in the level of Rev31, the presumed catalytic subunit of mammalian pol zeta, decreased damage-induced mutagenesis in human cell lines [3]. To study the function of mammalian Rev31, we inactivated the gene in mice. Two exons containing conserved DNA polymerase motifs were replaced by a cassette encoding G418 resistance and beta-galactosidase, under the control of the Rev3l promoter. Surprisingly, disruption of Rev3l caused mid-gestation embryonic lethality, with the frequency of Rev3l(-/-) embryos declining markedly between 9.5 and 12.5 days post coitum (dpc). Rev3l(-/-) embryos were smaller than their heterozygous littermates and showed retarded development. Tissues in many areas were disorganised, with significantly reduced cell density. Rev3l expression, traced by beta-galactosidase staining, was first detected during early somitogenesis and gradually expanded to other tissues of mesodermal origin, including extraembryonic membranes. Embryonic death coincided with the period of more widely distributed Rev3l expression. The data demonstrate an essential function for murine Rev31 and suggest that bypass of specific types of DNAlesions by pol zeta is essential for cell viability during embryonic development in mammals.

Animals↗
PubMed1999

Activation of Rad53 kinase in response to DNA damage and its effect in modulating phosphorylation of the lagging strand DNA polymerase.

The Saccharomyces cerevisiae Rad53 protein kinase is required for the execution of checkpoint arrest at multiple stages of the cell cycle. We found that Rad53 autophosphorylation activity depends on in trans phosphorylation mediated by Mec1 and does not require physical association with other proteins. Uncoupling in trans phosphorylation from autophosphorylation using a rad53 kinase-defective mutant results in a dominant-negative checkpoint defect. Activation of Rad53 in response to DNA damage in G(1) requires the Rad9, Mec3, Ddc1, Rad17 and Rad24 checkpoint factors, while this dependence is greatly reduced in S phase cells. Furthermore, during recovery from checkpoint activation, Rad53 activity decreases through a process that does not require protein synthesis. We also found that Rad53 modulates the lagging strand replication apparatus by controlling phosphorylation of the DNA polymerase alpha-primase complex in response to intra-S DNA damage.

Cell Cycle↗
PubMed1999

Effective depletion of alloreactive lymphocytes from peripheral blood mononuclear cell preparations.

BACKGROUND: T cells present in an allogeneic bone marrow transplant may produce graft-versus-host disease but also contribute to immune reconstitution and enhance engraftment. Our aim was to separate alloreactive from nonalloreactive T lymphocytes, by performing a mixed lymphocyte culture (MLC) stimulation of donor cells, followed by selective depletion of activated cells expressing the high-affinity interleukin 2 receptor. We then characterized the resulting depleted cell fraction. METHODS: Donor peripheral blood mononuclear cells were cocultured with irradiated peripheral blood mononuclear cells from HLA-nonidentical recipient stimulators in an MLC. After 3 days, CD25+ lymphocytes (alloreactive cells expressing the alpha chain of the interleukin 2 receptor) were removed by immunomagnetic separation. The depleted donor fraction and untreated cells were then rechallenged in a secondary MLC with the original irradiated stimulator cells or a third party to assess relative alloreactivity. RESULTS: Inhibition of the secondary MLC and of host-specific cytotoxic activities was observed as well as a disappearance of interleukin 2 receptor-positive cells. Alloreactivity against unrelated third-party cells was preserved. Limiting dilution analysis of residual alloantigen-reactive T lymphocytes demonstrated a 1.3 log reduction of antihost reactivity. The depletion largely removed host-specific alloreactive CD4+ cells. CONCLUSIONS: This method reduces alloreactivity while retaining reactivity against third-party targets. This approach may allow therapeutic infusion of T cells after HLA-nonidentical allografts with a reduced capacity to produce graft-versus-host disease.

Blood Component Removal↗
PubMed1999

Allogeneic hematopoietic transplantation as adoptive immunotherapy. Induction of graft-versus-malignancy as primary therapy.

An immune-mediated graft-versus-malignancy effect is important to prevent relapse after allogeneic bone marrow transplant for a range of hematologic malignancies and potentially some solid tumors. Graft-versus-leukemia (GVL) effects as seen in response to donor lymphocyte infusions have been most prominent against indolent malignancies including chronic myelogenous leukemia, chronic lymphocytic leukemia, and low-grade lymphoma. Acute myelogenous leukemia and multiple myeloma may also respond. An alternative strategy for allogeneic transplantation is to avoid the toxicity of high-dose chemoradiotherapy and use a relatively nontoxic, nonablative preparative regimen to achieve engraftment, allowing subsequent infusion of additional donor lymphocytes to mediate GVL. Fludarabine-based nonablative chemotherapy agents, using standard dose combinations, produce moderate myelosuppression but are sufficiently immunosuppressive to allow engraftment of an allogeneic hematopoietic transplant and generation of graft-versus-malignancy effects.

Antigens, Neoplasm↗
PubMed1997

A role for DNA primase in coupling DNA replication to DNA damage response.

The temperature-sensitive yeast DNA primase mutant pri1-M4 fails to execute an early step of DNA replication and exhibits a dominant, allele-specific sensitivity to DNA-damaging agents. pri1-M4 is defective in slowing down the rate of S phase progression and partially delaying the G1-S transition in response to DNA damage. Conversely, the G2 DNA damage response and the S-M checkpoint coupling completion of DNA replication to mitosis are unaffected. The signal transduction pathway leading to Rad53p phosphorylation induced by DNA damage is proficient in pri1-M4, and cell cycle delay caused by Rad53p overexpression is counteracted by the pri1-M4 mutation. Altogether, our results suggest that DNA primase plays an essential role in a subset of the Rad53p-dependent checkpoint pathways controlling cell cycle progression in response to DNA damage.

Blotting, Western↗