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S Molinari

Publications and source records attributed to S Molinari.

At least 19 recordsLinked to original sources
PubMed2004

The in vivo form of the murine class VI POU protein Emb is larger than that encoded by previously described transcripts.

The class VI POU domain family member known as Emb in the mouse (rat Brn5 or human mPOU/TCFbeta1) is present in vivo as a protein migrating at about 80 kDa on western blots, considerably larger than that predicted (about 42 kDa) from previously cloned coding sequences. By RT-PCR and 5' RACE strategies a full-length Emb sequence, Emb FL, is now identified. Shorter sequences encoding the -COOH terminal, and an -NH(2) terminal isoform, EmbN, were also isolated. Comparisons of Emb coding sequences between species, including the full-length zebra fish, POU(c), are presented, together with a compilation of the multiple transcripts produced by alternative splicing and the presence of different transcriptional start and stop sites, from the Emb gene.

Alternative Splicing↗
PubMed2004

A novel complex regulates cardiac actin gene expression through interaction of Emb, a class VI POU domain protein, MEF2D, and the histone transacetylase p300.

Expression of the mouse cardiac actin gene depends on a distal enhancer (-7 kbp) which has been shown, in transgenic mice, to direct expression to embryonic skeletal muscle. The presence of this distal sequence is also associated with reproducible expression of cardiac actin transgenes. In differentiated skeletal muscle cells, activity of the enhancer is driven by an E box, binding MyoD family members, and by a 3' AT-rich sequence which is in the location of a DNase I-hypersensitive site. This sequence does not bind MEF2 proteins, or other known muscle transcription factors, directly. Oct1 and Emb, a class VI POU domain protein, bind to consensus sites on the DNA, and it is the binding of Emb which is important for activity. Emb binds as a major complex with MEF2D and the histone transacetylase p300. The form of Emb present in this complex and as a major form in muscle cell extracts is longer (80 kDa) than that previously described. These results demonstrate the importance of this novel complex in the transcriptional regulation of the cardiac actin gene and suggest a potential role in chromatin remodeling associated with muscle gene activation.

Acetyltransferases↗
PubMed2001

Prosaposin treatment induces PC12 entry in the S phase of the cell cycle and prevents apoptosis: activation of ERKs and sphingosine kinase.

We report that prosaposin treatment induced extracellular signal-regulated kinases (ERKs) and sphingosine kinase activity, increased DNA synthesis, and prevented cell apoptosis. Prosaposin treatment induced pheochromocytoma cells (PC12) to enter the S phase of the cell cycle; this effect was inhibited by the MEK inhibitor PD98059, indicating that prosaposin-induced ERK phosphorylation is required for stimulation of DNA synthesis. The prosaposin effect was also inhibited by pertussis toxin, indicating that the prosaposin receptor is a G-protein-coupled receptor. Prosaposin rescued PC12 cells from apoptosis induced by staurosporine or ceramide. Sphingosine kinase activity was increased by prosaposin treatment. We propose that this effect is a mechanism underlying the proliferative and anti-apoptotic functions of prosaposin. Prosaposin appears to be a key regulatory factor in the ceramide-S-1-P rheostat, which regulates cell fate.

Adrenal Gland Neoplasms↗
PubMed2001

The nuclear localization domain of the MEF2 family of transcription factors shows member-specific features and mediates the nuclear import of histone deacetylase 4.

Targeting of myocyte enhancer binding factor 2 (MEF2) proteins to the nucleus depends on a C-terminal bipartite nuclear localization signal (NLS). By expression of green fluorescent protein (GFP)/MEF2 fusion proteins in transfected myoblasts, we show that MEF2C contains an additional 13 amino acids domain, located immediately upstream of the NLS, which contributes to its nuclear retention. We also show that the NLS present in MEF2 proteins is required for efficient nuclear localization of histone deacetylase 4 (HDAC4). In muscle cells, transfected HDAC4 is largely cytoplasmic or, to a lesser extent, pancellular. Co-transfection of either MEF2A or MEF2C causes HDAC4 to accumulate in the nucleus in association with MEF2. This effect strongly depends on MEF2 NLS; it also requires the specific interaction of HDAC4 with MEF2, since the isolated NLS is not sufficient for targeting HDAC4 to the nucleus and other nuclear proteins, such as NF-Y, cannot substitute MEF2. Therefore, we demonstrate that HDAC4, different from HDAC5, is mainly a cytoplasmic resident protein, requiring a trans-acting NLS for nuclear localization. The physiological implications of MEF2 carrying its own inhibitor to the nucleus are discussed.

Active Transport, Cell Nucleus↗
PubMed2000

Is SIB or BNP better than MMSE in discriminating the cognitive performance of severely impaired elderly patients?

The sensitivity of the Mini Mental State Evaluation (MMSE) in severely impaired patients is reduced by a floor effect and limited score range. The Severe Impairment Battery (SIB) and Preliminary Neuropsychological Battery (BNP) may be valid alternatives. We studied a group of 37 severely compromised elderly inpatients to investigate the usefulness of these two test batteries as alternatives to the MMSE. Both proved reliable, but only the SIB had a wider distribution of results with respect to the MMSE in the lower score range. The BNP, that might be thought easier to perform being a simple verification task, could actually not be completed by the most compromised patients. The SIB seems better able than the MMSE to provide cognitive profile in the three diagnostic categories into which patients were subdivided (Psychogeriatric, Psychorganic, Mentally Retarded). We conclude that it may be useful to test patients with the SIB when they yield a MMSE score lower than 10-12 points.

Journal Article↗
PubMed1998

Sensitization to green coffee beans and work-related allergic symptoms in coffee workers.

BACKGROUND: Occupational respiratory allergy to green coffee beans (GCB) and to castor beans (CB) was studied in 112 workers in a modern coffee manufacturing plant of Trieste (Italy), where the process is completely automatic, the environmental conditions are good and where exposure to CB can be considered absent because since 1970, only new sacks have been used for coffee transportation. METHODS: All subjects were interviewed by a trained doctor using a questionnaire to investigate allergic symptoms and predisposing factors. Sensitization to GCB and to common allergens (pollens, molds, house dust mites) were evaluated by the skin-prick test. The serum of subjects with a positive skin-prick test to CGB or who had symptoms at work was tested for specific IgE (RAST) for GCB and CB. Lung function was evaluated by a Ponigraph spirometer. RESULTS: Sensitization to GCB was found in 25.8% of green coffee workers (31 cases), in 2.7% of roasted coffee workers (37 cases) and in 4.5% of the clerks (44 cases), p < 0.01. The evaluation of IgE specific for CB gave positive results only in 3 of 10 subjects sensitized to GCB. A total of 20% of GCB workers (6 cases) complained of work-related respiratory symptoms (asthma and/or rhinitis) compared with only one subject in the roasted coffee group and one in the control group (p < 0.01). Asthma was reported by 2/31 of the green coffee workers and by 1/44 of roasted coffee workers. CONCLUSIONS: There was a significant correlation between sensitization to GCB and work related symptoms (p < 0.01), common allergic symptoms (p < 0.05) and atopy by prick test (< 0.01). These results point to the need to evaluate atopic status in workers and identify the most susceptible subjects, with the aim of informing them of their at-risk status and monitoring their progress. This makes it possible to diagnose sooner those symptoms possibly indicative of a work-related disease, because even in presence of good environmental conditions and even when symptoms are mild, it is almost always the atopic subjects who are affected.

Adult↗
PubMed1998

Picture naming and progression of Alzheimer's disease: an analysis of error types.

Seven patients affected by Dementia of the Alzheimer Type (DAT) took part in a longitudinal study aimed at assessing the qualitative and quantitative evolution of picture naming impairment. The follow-up lasted 6-36 months and the patients were examined at intervals of 6 months or longer. We found that the absolute number of lexical-semantic errors tended to be constant or to rise slightly until an advanced stage of DAT severity was reached. However, the proportion of errors of the lexical-semantic type in relation to the overall number of errors showed a decline as the disease progressed, with empty and unrelated responses being increasingly observed. Visual errors were generally a minority; they were produced in different proportions for each patient but did not vary greatly over time. For the observed patients, the proportion of lexical and semantic errors was inversely related to the overall naming performance, following a negative logarithmic function. This finding was replicated analysing cross-sectional data from another 24 DAT patients who were given the same naming task.

Aged↗
PubMed1998

[Percutaneous needle biopsy guided with computerized tomography of the chest. Personal experience with 1,605 cases].

INTRODUCTION: Fine-needle aspiration biopsy (FNAB) plays an important role in the diagnosis of lung diseases. We report the results of 1605 CT-guided chest biopsies performed September, 1992, to December, 1997, and introduce a new method for specimen storage and handling. MATERIALS AND METHODS: A lubricated flexible connection was placed between the needle and the syringe to cushion the improper movements transmitted on the needle by the operator during aspiration. 22-G needles were most frequently used. The pathologist's report included not only the presence/absence of tumor cells, but also the presence of suspicious/questionable cells, which latter finding led to another biopsy in 152 cases. RESULTS: 64.7% of the lesions were < or = 3 cm and 55.5% were < or = 2 cm. Pneumothorax occurred in 16.0% of cases and it required a chest tube in 5.0%. The specimens were not smeared on a slide but kept in a test tube and quickly sent to the pathologist. 84.3% of the specimens were adequate for diagnosis and special care was given to typifying microcytoma/non-microcytoma histotypes, because treatment is different. 1003 of 1313 cases (76.38%) were true positives, 192 (14.2%) true negatives, 101 (7.69%) false negatives and 17 (1.92%) false positives. Sensitivity was 90.85%, specificity 91.86% and diagnostic accuracy 91.01%. The positive and the negative predictive values were 98.3% and 65.5%, respectively. CONCLUSIONS: The use of a 60 mL syringe with a flexible connection reduces the rate of complications (eg, pneumothorax, bleeding) and also the biopsy time. It also improved the sampling accuracy, cushioning any possible inappropriate movement by the operator, and finally improved the material aspiration thanks to better vacuum than with the 20-30 mL syringes which are usually placed into biopsy guns.

Adolescent↗
PubMed1997

Liver function alterations in synthetic leather workers exposed to dimethylformamide.

A cross-sectional study of the prevalence of chronic liver function alterations was performed in 75 workers employed in a synthetic leather factory, exposed to dimethylformamide (DMF) air concentrations below threshold limit values (30 mg/m3). Biological monitoring among workers revealed acceptable urine levels of monomethylformamide (NMF) on average, but the very wide range indicated that occasional overexposure was possible. The worker survey showed a high percentage of disulfiram-like symptoms (50%) and liver function abnormalities (22.7%), compared with a demographically similar group of unexposed workers. Covariance analysis (ANCOVA) revealed that enzyme levels were significantly higher in exposed workers than in controls after data were corrected for age, alcohol consumption, body mass index, and cholesterol levels. The authors conclude that DMF can cause liver diseases even if air TLVs are respected, because accidental contact with liquid DMF can significantly increase DMF uptake. In this situation, air monitoring is no longer sufficient to evaluate worker exposure.

Adult↗
PubMed1997

Prolonged therapy with ACE inhibitors induces a regression of left ventricular hypertrophy of dialyzed uremic patients independently from hypotensive effects.

Left ventricular hypertrophy (LVH), which frequently occurs in chronic uremia, may be due in part to factors other than arterial hypertension, chronic anemia, and/or other well-known loading conditions inherent to the uremic state. Angiotensin-converting enzyme (ACE) inhibitors may be able to reverse LVH by mechanisms independent of their antihypertensive effects. In this study, 18 subjects free of arterial hypertension or severe anemia were selected from 170 chronically hemodialyzed uremic patients after fulfilling the criterion of a supranormal left ventricular mass (LVM). Ten subjects agreed to undergo treatment with 2.5 to 20 mg lisinopril every other day over a period of 2 years, during which annual determinations of the LVM by echocardiography and of the 24-hour blood pressure with a portable device were carried out. Eight patients unwilling to undergo the treatment served as controls. The average resting left ventricular mass index (LVMi) of the overall group was 178 +/- 30 g/m2 body surface area (+/- SD), and did not differ between the two subgroups. Lisinopril treatment significantly decreased the LVM of eight of 10 treated subjects and actually even completely normalized it in three. The LVM of the untreated group remained unchanged. Systolic and diastolic blood pressures were 138 +/- 5 mm Hg and 78 +/- 6 mm Hg in the treated group and 133 +/- 9 mm Hg and 75 +/- 4 mm Hg in the untreated group, respectively (P = NS), and did not vary over the following 2 years. This study indicates that a mild degree of LVH, which is seemingly independent of arterial blood pressure load, does exist in a tight subset of uremic patients. This study also demonstrates that this type of LVH is apparently nonprogressive. ACE inhibitors given at doses not affecting blood pressure are able to reverse it.

Aged↗
PubMed1997

Absence of MEF2 binding to the A/T-rich element in the muscle creatine kinase (MCK) enhancer correlates with lack of early expression of the MCK gene in embryonic mammalian muscle.

During skeletal muscle development, different types of muscle fibers are generated, which express different combinations of muscle-specific gene products. For example, the muscle creatine kinase gene (MCK) is highly expressed in fetal but not embryonic myotubes. We performed transient transfections of CAT reporter constructs, driven by the MCK promoter with variable lengths of 5'-flanking sequence, into primary cultures of embryonic and fetal muscle cells. Reporter activity was observed in fetal but not embryonic muscle cells. We assayed the ability of nuclear extracts prepared from embryonic and fetal muscle and C2C12 myotubes to bind specific regulatory elements in the MCK enhancer. The profile of DNA/protein complexes resulting from electrophoretic mobility shift assays was qualitatively the same with all extracts used when the oligonucleotide probes represented the MCK-E-box, MHox site, CArG-box, and AP2 site. In contrast, no binding activity to the MEF2 site was observed with embryonic nuclear extract. Interestingly, MEF2 mRNAs and proteins were detected in both fetal and embryonic muscle, with the exception of the MEF2D1b isoform, which is restricted to fetal muscle. Furthermore, we found that protein phosphatase inhibitors included in the preparation of embryonic nuclear extracts or added to the medium of transfected embryonic myotubes can restore MEF2 DNA binding activity, as well as reporter activity driven by the MCK promoter and partial transcriptional activation of the endogenous MCK gene. We propose that phosphorylation of MEF2 regulates its activity and represents an important aspect of the mechanism controlling stage-specific transcription during skeletal myogenesis.

Alkaline Phosphatase↗
PubMed1996

Deficits in memory and hippocampal long-term potentiation in mice with reduced calbindin D28K expression.

The influx of calcium into the postsynaptic neuron is likely to be an important event in memory formation. Among the mechanisms that nerve cells may use to alter the time course or size of a spike of intracellular calcium are cytosolic calcium binding or "buffering" proteins. To consider the role in memory formation of one of these proteins, calbindin D28K, which is abundant in many neurons, including the CA1 pyramidal cells of the hippocampus, transgenic mice deficient in calbindin D28K have been created. These mice show selective impairments in spatial learning paradigms and fail to maintain long-term potentiation. These results suggest a role for calbindin D28K protein in temporally extending a neuronal calcium signal, allowing the activation of calcium-dependent intracellular signaling pathways underlying memory function.

Animals↗
PubMed1996

The diagnostic value of imaging the patient with dizziness. A Bayesian approach.

BACKGROUND: Imaging studies are routinely used in the evaluation of patients with dizziness. A principal concern of the ordering physician is to rule out a cerebellopontine angle (CPA) mass. The incidence of such masses in patients presenting with dizziness is quite low, however, raising the question of the value of imaging this population. OBJECTIVE: To calculate the probability, using Bayes theorem, that a given patient with dizziness has a CPA mass. DESIGN: Meta-analysis of epidemiological data on CPA masses and of studies reporting the incidence of otologic symptoms in patients with these masses. We also conducted a study of consecutive patients with dizziness to determine the frequency of asymmetric hearing loss in this population. These data were combined in applications of Bayes theorem to calculate disease probabilities. RESULTS: The probability that a patient with dizziness has a CPA mass is 0.0004, indicating that 2500 imaging studies would have to be performed to identify 1 CPA mass. If patients with subjectively normal hearing are investigated (ie, those with isolated dizziness), the probability is 0.000107, indicating that 9307 scans would have to be performed to identify 1 CPA mass. If the search is restricted to those patients with dizziness and asymmetric hearing loss (the patients usually felt to be high risk), the probability is 0.00156, indicating that 638 scans would have to be performed to identify 1 CPA mass. CONCLUSIONS: Even when studying patients with dizziness and asymmetric hearing loss, the probability of identifying a CPA mass is sufficiently low that we do not feel imaging is generally warranted. When faced with a patient with dizziness, we recommend a careful neurologic and otologic examination. If abnormalities are detected on examination that suggest central nervous system disease or invasive otologic disease, imaging should be pursued as appropriate. In cases of acute vertigo, if the patient is at high risk for cerebrovascular disease by virtue of age and additional risk factors, imaging should probably be pursued. For the remainder of patients, if progression of hearing loss is not documented, we do not believe imaging is warranted. Progressive hearing loss with abnormal speech reception thresholds probably warrants a magnetic resonance imaging scan of the internal auditory canals.

Aged↗
PubMed1995

Serum cholesterol concentrations in parasuicide.

OBJECTIVE: To evaluate whether people who have committed parasuicide have low serum cholesterol concentrations. DESIGN: Results of blood tests in subjects admitted to hospital for parasuicide compared with those of a control group of non-suicidal subjects; comparison in subgroup of parasuicide subjects of two sets of blood test results (one set from admission for parasuicide and the other from admission for some other illness). SETTING: General hospital, Ferrara, Italy. SUBJECTS: 331 parasuicide subjects aged 44 (SD 21) years (109 with two sets of blood test results) and 331 controls. MAIN OUTCOME MEASURES: Serum cholesterol concentrations and possible association with parasuicide, considering sex, violence of method of parasuicide, and underlying psychiatric disorder. RESULTS: Lower serum cholesterol concentrations (4.96 (SD 1.16) mmol/l) were found in the parasuicide subjects than in the controls (5.43 (1.30); P < 0.001), regardless of sex and degree of violence of parasuicide method. Both men and women with two sets of blood test results had lower cholesterol concentrations after parasuicide. Linear regression analysis showed that the difference in cholesterol concentrations was significantly related to the length of time between the taking of the two sets of blood samples. CONCLUSION: The study showed low cholesterol concentrations after parasuicide. This finding agrees with previous studies, which suggest an association between low cholesterol concentration and suicide.

Adult↗
PubMed1995

Modeling incidence rate ratio and rate difference: additivity or multiplicativity of human immunodeficiency virus parenteral and sexual transmission among intravenous drug users. Northern Italy Seronegative Drug Addicts Study.

The analysis concerns data from the Northern Italian Seronegative Drug Addicts Study, a multicenter longitudinal study about the incidence of human immunodeficiency virus infection in intravenous drug users from Milan and other areas of northern Italy between 1987 and 1991. Different measures of parenteral and heterosexual exposure effects were estimated by fitting multiplicative models for rate ratio and additive models for both rate ratio and rate difference into a Poisson regression model for grouped cohort data. In areas of high human immunodeficiency virus prevalence among intravenous drug users, the adjusted rate ratio under a multiplicative structure was 6.2 (95% likelihood-based confidence interval (LCI) 2.9-14.4) for parenteral and 2.9 (95% LCI 1.3-6.1) for sexual transmission. Under the additive model, the rate ratio was 7.8 (95% LCI 3.4-20.2) for parenteral and 9.2 (95% LCI 2.2-29.7) for sexual transmission, and the rate difference per 100 person-years was 9.8 (95% LCI 5.3-15.6) for parenteral and 10.5 (95% LCI 1.8-24.2) for sexual transmission (controlled for each other). Because of the small sample size, a clear discrimination between models could not be reached. However, in spite of the greater risk associated with parenteral transmission under a multiplicative model, the additive model suggests that the relative impact of measures aimed at inducing condom use is similar to that which would be obtained by measures aimed at stopping syringe sharing.

Blood-Borne Pathogens↗
PubMed1995

Human transplacental transfer of carbidopa/levodopa.

A paucity of information is available concerning the use of levodopa and carbidopa during pregnancy. Particularly lacking is whether these agents cross the placenta and whether levodopa undergoes metabolism in the fetus. The present study carried out in aborted fetal tissues demonstrates that levodopa crosses the placental barrier and suggests that it may be metabolized in fetal tissues, including the brain and spinal cord. The possibility exists that early exposure to levodopa or dopamine may alter the normal neuronal development in the fetus, and caution in the use of levodopa during pregnancy should be observed.

Antiparkinson Agents↗
PubMed1995

Pre-employment screening among trainee bakers.

OBJECTIVES: To assess the prevalence of atopy in a vocational school so as to evaluate the feasibility of pre-employment screening. METHODS: The prevalence of atopy by family diathesis, prick tests, immunoglobulin E (IgE) concentrations, and personal history of allergic respiratory diseases was investigated in 144 trainee bakers and 81 students on a graphic artists course (mean age 15.4 years). Skin sensitisation to wheat, rye, and barley flours, to alpha amylase, and to storage mites was also evaluated. RESULTS: Personal allergic symptoms were reported by 13.2% of the bakers and 14.7% of the graphic artists and there was a significant association between symptoms and atopy by prick tests (odds ratio (OR) 17.2; 95% confidence interval (95% CI) 5.27-56.4) and by family history (OR 3.11; 95% CI 1.02-9.53). When bakers were grouped according to the presence of allergic symptoms and results of immunological tests, 6.9% had asthma, 6.3% had rhinoconjunctivitis, and a high percentage (28.5%) were without symptoms but scored positive on prick tests or family symptoms. Skin sensitisation to storage mites had similar prevalences (16%) in the two groups of trainees and occurred nearly always in atopic people. Positive skin tests to wheat flour (3.5%), rye (0.7%), and alpha amylase (0.7%) were specific to bakers. CONCLUSIONS: Pre-employment screening is a useful source of medical information and allows for counseling. The presence of asthma, or of another allergic disease in a severe form, is suggested as a criterion for excluding students of a vocational school from training as bakers. Student bakers without allergic symptoms but atopic by other criteria should be informed about their risks of developing occupational asthma, and periodic check ups must be recommended. Screening studies in vocational school provide a better understanding of specificity of skin sensitisation to occupational allergens.

Adolescent↗