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Biomedical subjects

F Casagrande

Publications and source records attributed to F Casagrande.

At least 19 recordsLinked to original sources

Measurements of the generalized electric and magnetic polarizabilities of the proton at low Q2 using the virtual-compton-scattering reaction.

The mean square polarizability radii of the proton have been measured for the first time in a virtual-Compton-scattering experiment performed at the MIT-Bates out-of-plane scattering facility. Response functions and polarizabilities obtained from a dispersion analysis of the data at Q2 = 0.057 GeV2/c2 are in agreement with O(p3) heavy baryon chiral perturbation theory. The data support the dominance of mesonic effects in the polarizabilities.

Journal Article↗

Investigation of the conjectured nucleon deformation at low momentum transfer.

We report new precise H(e,e(')p)pi(0) measurements at the Delta(1232) resonance at Q(2)=0.127 (GeV/c)(2) obtained at the MIT-Bates out-of-plane scattering facility which are particularly sensitive to the transverse electric amplitude (E2) of the gamma(*)N-->Delta transition. The new data have been analyzed together with those of earlier measurements to yield precise quadrupole to dipole amplitude ratios: Re(E(3/2)(1+)/M(3/2)(1+))=(-2.3+/-0.3(stat+syst)+/-0.6(model))% and Re(S(3/2)(1+)/M(3/2)(1+))=(-6.1+/-0.2(stat+syst)+/-0.5(model))% for M(3/2)(1+)=(41.4+/-0.3(stat+syst)+/-0.4(model))(10(-3)/m(pi(+))). The derived amplitudes give credence to the conjecture of deformation in hadrons favoring, at low Q2, the dominance of mesonic effects.

Journal Article↗

Prenatal diagnosis of a craniopharyngioma: a new case with radical surgery and review.

CASE REPORT: A case of the antenatal diagnosis of a craniopharyngioma with radical surgery in the neonatal period is reported. REVIEW OF THE LITERATURE: We have reviewed the literature of such cases in an attempt to isolate specific features in this age group and to determine the appropriate management. Only six cases of the truly antenatal diagnosis of craniopharyngiomas have been reported. Diagnosis has resulted from routine ultrasound during pregnancy or from polyhydramnios. Clinically, there is often macrocephaly due to hydrocephalus or a significant-sized tumor. CONCLUSIONS: Management of these rare cases is controversial with high postoperative mortality and significant morbidity, including panhypopituitarism, visual disturbance, and neuropsychological disorders. From the available literature, no conclusions concerning the management can be drawn at present, due to the rarity of early surgical intervention. Our case, despite the lack of important follow-up, seems to confirm the possibility of attempting radical surgery in the neonatal period as a result of advances both in surgical techniques and in neonatal intensive care.

Adult↗

Pharmacological complications of the chronic baclofen infusion in the severe spinal spasticity. Personal experience and review of the literature.

AIM: To evaluate the pharmacological complications and side effects of the chronic intrathecal baclofen infusion in patients suffering from intractable spinal spasticity in our Department as well as in the literature. METHODS: The pharmacological complications and side effects observed at long-term follow-up in 25 patients with chronic intrathecal baclofen infusion are evaluated; the search of the literature complications was carried out in Medline and in Ingenta web sites. RESULTS: We have been able to observe in our series 3 (12%) patients with hypotonia, 2 with impairment on erection (8%) and 1 (4%) with constipation; 5 (20%) patients showed also tolerance but only 1 (4%) needed a ''drug holiday''. In the literature the side effects range from 4% to 16%. Moreover the tolerance is reported from 3% to 15%. The overdose has been reported from 0% to 14%, while the syndrome of withdrawal is reported in 16 patients with 6 fatalities. In our series these two last complications were not observed. CONCLUSIONS: Lethal pharmacological complications are rare and, if promptly diagnosed and treated, are reversible. Side effects of minor importance can impair the patient quality of live and needed to be adjusted to patient's requirements. This kind of therapy should be restricted to specialized centres.

Adult↗

How to measure the phase diffusion dynamics in the micromaser.

We propose a realistic scheme for measuring the micromaser linewidth by monitoring the phase diffusion dynamics of the cavity field. Our strategy consists of exciting an initial coherent state with the same photon number distribution as the micromaser steady-state field, singling out a purely diffusive process in the system dynamics. After the injection of a counterfield, measurements of the population statistics of a probe atom allow us to derive the micromaser linewidth in all ranges of the relevant parameters, establishing experimentally the distinctive features of the micromaser spectrum due to the discreteness of the electromagnetic field.

Journal Article↗

Long-term intrathecal Baclofen infusion in supraspinal spasticity of adulthood.

OBJECTIVE: To evaluate long-term results of chronic intrathecal Baclofen infusion on the spasticity, on the spasms and to evaluate the side-effects of the intrathecal Baclofen in patients with supraspinal spasticity. CLINICAL MATERIALS AND METHODS: Fourteen patients with severe progressive refractory to medical therapy spasticity were evaluated after chronic intrathecal Baclofen infusion performed by implantation of subcutaneous pump. The patients had suffered traumatic or anoxic acquired brain injuries. The clinical evaluation was made using Ashworth Scale (AS) and the Spasm Frequency Scale (SFS). RESULTS: The intrathecal therapy showed a statistically significant improvement of the tone and of the spasms. CONCLUSIONS: The intrathecal infusion of Baclofen seems to be an effective treatment in patients with supraspinal spasticity.

Adolescent↗

Predictive value of ANCA in atypical primary brain localization of Wegener's granulomatosis.

Wegener's Granulomatosis is a necrotizing vasculitis generally involving upper and lower respiratory tract and kidneys. The central nervous system is involved in less than 10% of the patients during the course of the disease and primary involvement is even rarer. We present and discuss the case of a patient with primitive cerebral localization of Wegener's Granulomatosis in which the diagnosis and the beginning of correct therapy were delayed, in spite of a rising c-ANCA titer, due to a misinterpretation of a bioptic specimen. This delay caused renal damage and pulmonary cavitations which needed a long time to recover. This case report suggests that the central nervous system can be the site of a primary localization of Wegener's Granulomatosis even without any other organ involvement. The diagnosis must be made as soon as possible in order to prevent spread to other sites since the disease is usually very aggressive and severe.

Antibodies, Antineutrophil Cytoplasmic↗

Measurement of the elastic magnetic form factor of (3)He at high momentum transfer.

New electron scattering measurements have been made that extend data on the (3)He elastic magnetic form factor up to Q(2) = 42.6 fm(-2). These new data test theoretical conjectures regarding non-nucleonic effects in the three-body system. The very small cross sections, as low as 10(-40) cm(2)/sr, required the use of a high-pressure cryogenic gas target and a detector system with excellent background rejection capability. No existing theoretical calculation satisfactorily accounts for all the available data.

Journal Article↗

Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1.

We have investigated the effects of a series of flavonoids on cell proliferation and cell cycle distribution in human melanoma cells OCM-1. Among the compounds that potently inhibited OCM-1 cell proliferation, we show that the presence of a hydroxyl group at the 3'-position of the ring B in quercetin and luteolin, correlated to a G1 cell cycle arrest while its absence in kaempferol and apigenin correlated to a G2 block. Genistein with a hydroxyl at 5-position of the ring A arrested cells in G2 while daidzein which lacks it, induced an accumulation of cells in G1. We demonstrate that flavonoids, which induced a cell cycle block in G1, inhibited the activity of CDK2 by 40-60%. By contrast, those which caused an accumulation of cells in G2/M were without effect. On the other hand, while quercetin, daidzein and luteolin did not alter the activity of CDK1, kaempferol, apigenin and genistein inhibited this kinase by 50-70%. We demonstrate that the up-regulation of the CDK inhibitors p27(KIP1) and p21(CIP1) is likely responsible for the inhibition of CDK2 while inhibition of CDK1 was rather due to the phosphorylation of the kinase on Tyr15 residue.

CDC2 Protein Kinase↗

Proinflammatory cytokines inhibit secretion in rat bile duct epithelium.

BACKGROUND AND AIMS: Cholestatic disorders often are associated with portal inflammation, but whether or how inflammation contributes to cholestasis is unknown. Thus we studied the effects of proinflammatory cytokines on bile duct epithelia secretory mechanisms. METHODS: Isolated bile duct units (IBDUs) were cultured with interleukin (IL)-6, interferon gamma, tumor necrosis factor (TNF)-alpha, and IL-1 alone or in combination. Ductular secretion was measured using video-optical planimetry. Bicarbonate and Cl(-) transport were assessed microfluorimetric measuring pH(i) (BCECF) and [Cl(-)](i) transients (MEQ). Expression of Cl(-)/HCO(3)(-) exchanger (AE-2), cystic fibrosis transmembrane conductance regulator (CFTR), and the secretin receptor (SR) were assessed by ribonuclease protection assay. Cellular cyclic adenosine monophosphate (cAMP) levels were studied by enzymatic immunoassay. Paracellular permeability was assessed using fluorescein-labeled dextrans (FD) in cholangiocyte monolayers (NRC-1). RESULTS: Although not effective when given alone, each combination of IL-6, interferon gamma, IL-1, and TNF-alpha inhibited secretion in IBDU. Cytokines inhibited cAMP formation, AE-2 activity, and cyclic AMP-dependent Cl(-) efflux, but not that induced by purinergic agonists. AE-2 gene expression was unaffected by proinflammatory cytokines, whereas CFTR and SR expression was increased. In addition, paracellular transit of FD across NRC-1 monolayers was increased. CONCLUSIONS: Inflammatory cytokines inhibit cAMP-dependent fluid secretion in cholangiocytes and impair the barrier functions of biliary epithelia. These changes may represent the molecular mechanisms by which inflammation leads to ductular cholestasis in vivo.

Animals↗

Radiotherapy for a solitary brain metastasis during pregnancy: a method for reducing fetal dose.

A patient presented during the second half of pregnancy with a solitary brain metastasis from lung cancer. This case shows that, using a new patient position, it is possible to shield the fetus efficiently. This new method consisted of whole brain irradiation with parallel pair treatment by lateral fields with the patient in a supine position with maximal neck extension. The dose to the fetus has been considerably reduced (0.3 cGy total dose) compared with previous techniques. The prescribed tumour dose was 30 Gy.

Adult↗

p21CIP1 is dispensable for the G2 arrest caused by genistein in human melanoma cells.

We have investigated the effect of genistein on cell cycle distribution of the human choroidal melanoma cell line OCM-1. We report that this isoflavonoid arrested cells in G2. This effect was correlated with the induction of the CDK inhibitor p21CIP1. However, while CDK1 activity was markedly reduced following genistein treatment, CDK2 activity was not affected. This was in agreement with the absence of G1 arrest that we observed but caused some doubt about the functionality of p21CIP1. Attempts to demonstrate mutation or post-translational modification of p21CIP1 from OCM-1 cells were unsuccessful. In fact, the level of p21CIP1 induced by genistein was shown to be insufficient to cause CDK2 inhibition. The role of p21CIP1 in the inhibition of CDK1 was questionable, as we demonstrated that genistein impaired Tyr15 dephosphorylation of CDK1 and because CDK1-cyclin B1 complexes from treated cells could be reactivated upon exposure to CDC25 phosphatase. Finally, we report that p21CIP1 was not absolutely required for the genistein-induced G2 arrest, as the isoflavone caused at least partial G2 arrest in p21-deficient Rat-1 fibroblasts as well as in p21-/- mouse embryo fibroblasts.

Animals↗

Distinct Chk2 activation pathways are triggered by genistein and DNA-damaging agents in human melanoma cells.

Genistein, a natural isoflavone found in soybeans, exerts a number of biological actions suggesting that it may have a role in cancer prevention. We have previously shown that it potently inhibits OCM-1 melanoma cell proliferation by inducing a G(2) cell cycle arrest. Here we show that genistein exerts this effect by impairing the Cdc25C-dependent Tyr-15 dephosphorylation of Cdk1, as the overexpression of this phosphatase allows the cells to escape G(2) arrest and enter an abnormal chromatin condensation stage. Caffeine totally overrides the genistein-induced G(2) arrest, whereas the block caused by etoposide is not bypassed and that caused by adriamycin is only partially abolished. We also report that genistein activates the checkpoint kinase Chk2 as efficiently as the two genotoxic agents and that caffeine may counteract the activation of Chk2 by genistein but not by etoposide. In contrast, caffeine abolishes the accumulation of p53 caused by all the compounds. Wortmannin does not suppress the Chk2 activation in any situation, suggesting that the ataxia telangiectasia-mutated kinase is not involved in this regulation. Finally, unlike etoposide and adriamycin, genistein induces only a weak response in terms of DNA damage in OCM-1 cells. Taken together, these results suggest that the G(2) checkpoints activated by genistein and the two genotoxic agents involve different pathways.

Caffeine↗

Long-term persistence of low bone density in orthotopic liver transplantation.

We determined bone density and metabolism in 46 patients (35 males, 11 females) who had undergone liver transplantation 1-48 months previously. Twenty-one patients were then followed for the next 24 months. At each visit, blood and urine samples for bone and liver metabolism parameters, as well as spinal and femoral dual-energy X-ray absorptiometry (DXA) scans, were obtained. Basal spinal and femoral density was low (p < 0.001). Patients with pre-transplant cholestatic diseases had lower spinal density than all the other subjects (p <0.05) and the cumulative methylprednisolone intake was an independent negative predictor of total hip density (p < 0.02). At baseline, urinary hydroxyproline and N-telopeptide were at the upper normal level and decreased only after 24 months of follow-up (p < 0.05). During the first year of follow-up, femoral density decreased (p < 0.05) and a partial recovery was observed for both spine and femur after 24 months. After 12 months, femoral bone density was negatively associated with serum cyclosporin A levels (p < 0.005) and cumulative methylprednisolone intake (p < 0.05), while the percent decrease in spinal density after the first 12 months was negatively predicted by mean daily methylprednisolone intake (p < 0.05). In patients with pre-transplant cholestatic diseases, femoral and spinal density increased after the first (p < 0.05) and second year (p < 0.05), respectively. In patients with previous post-necrotic cirrhosis, femoral density decreased after 12 months (p<0.05) and was still lower than baseline after 24 months (p < 0.05). However, at the end of the study the cumulative percentage of femoral neck osteoporosis was 43%. In conclusion, an elevated prevalence of spinal and femoral osteoporosis is present even many years after liver transplantation, with immunosuppressive treatment and pre-transplant liver disease being the most important pathogenetic factors.

Adult↗

Regulation by transforming growth factor-beta 1 of G1 cyclin-dependent kinases in human retinal epithelial cells.

Transforming growth factor beta (TGFbeta) is a potent inhibitor of epithelial cell proliferation, delaying or arresting cell cycle progression in mid-late G1. In long-term life span cells this growth inhibitory action has been attributed to regulatory events on both the levels and activities of G1 cyclin-dependent kinases (CDKs). CDK inhibitors have been shown to play important role in the TGFbeta-induced inhibition of G1 CDKs. In this work, we have investigated the effect of TGFbeta1 on both cell proliferation and G1 CDK activities in primary cultures of human retinal pigment epithelial (RPE) cells. We show that TGFbeta1 exerts a partial inhibitory effect on RPE cell proliferation by causing a significant increase of the RPE cell number in G1. TGFbeta1 induces an up-regulation of the CDK inhibitor p15(INK4B)with its subsequent association to CDK4, and a decline in CDK4 protein level. In parallel, we have observed a decline of p27(KIP1)associated to CDK4 and a significant increase of the inhibitor associated to CDK2. Finally, we show that TGFbeta1 reduces both CDK4 and CDK2 enzymatic activities. The fact that TGFbeta exerts only partial inhibitions on G1 CDKs and cell cycle progression in RPE cells suggests a propensity of these cells to escape from the anti-proliferative action of the cytokine, a phenomenon which could be reinforced during the development of proliferative vitreoretinopathy.

Blotting, Western↗

The monoethylglycinexylidide test for grading of liver cirrhosis.

BACKGROUND: Monoethylglycinexylidide (MEGX) formation following lignocaine injection has recently been proposed as a simple dynamic liver function test based on a single measurement of its serum concentration. AIM: To determine the optimal sampling time for MEGX determination. METHODS: A modelling analysis of lignocaine and MEGX kinetics was performed in seven normals and in four patients with compensated liver cirrhosis; a similar study was performed in 74 cirrhotic patients, divided into two groups according to disease severity (Pugh score). RESULTS: Only the MEGX fractional formation rate (kf) and formation delay (tau) were significantly altered in cirrhotic patients compared to normals: kf = 0.15 +/- 0.03 vs. 0.32 +/- 0.10 min-1 (mean +/- s.d.); tau = 7.7 +/- 2.0 vs. 3.9 +/- 2.9 min-1. A good correlation was found between kf and late (r = 0.82) but not early (r = 0.63) serum MEGX formation, suggesting that late measurements for the clinical MEGX test are preferred. In the second part of our investigation, by discriminant analysis of MEGX test data for 74 cirrhotic patients, the late MEGX concentrations gave the best discrimination between the two classes. In particular, the 60 min MEGX concentration showed the best diagnostic accuracy (81%), sensitivity (75%) and specificity (84%). The association of this with other MEGX parameters, either singly or derived from the whole curve measurements, did not improve the performance of the method. CONCLUSION: The MEGX test, based on a single determination 60 min after lignocaine injection, may be regarded as a simple and sensitive quantitative liver function test.

Adult↗

[Cyclin-dependent kinase inhibitory proteins in normal and transformed choroidal melanocytes].

PURPOSE: Recent studies have demonstrated the close link between oncogenesis and cell cycle machinery. Cyclin dependent kinase inhibitory proteins (Ckis) have been shown to be implicated in cancer progression. We investigated the levels of the different regulatory inhibitory proteins involved in the G1 progression and G1/S in choroidal melanomas. METHODS: Immunoblotting, immunoprecipitation and immunohistochemistry were performed on human choroidal cell lines and human choroïdal tumors. RESULTS: Our findings suggested a lack of expression of Cdk inhibitor p21 in two of three melanoma cell lines and a striking underexpression of p27 in the three transformed cell lines. The p16 level was found to be almost the same in both normal and transformed cells, a loss of p16-Cdk4 interaction was observed in two of the three melanoma cell lines. In immunohistochemistry, nuclear positivity for p16 was observed in six tumors. Nuclear positivity for p21 was observed in five tumors. All of theses tumors had scleral invasion (p = 0.003). Nuclear positivity for p27 was observed in only two tumors. CONCLUSION: Our results demonstrate that immunoreactivity for p16, p21 and p27 could be implicated in progression of melanoma tumors. More cases are required to further clarify this issue.

Cell Cycle↗