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Biomedical subjects

M Cecchini

Publications and source records attributed to M Cecchini.

At least 19 recordsLinked to original sources

A molecular dynamics approach to the structural characterization of amyloid aggregation.

A novel computational approach to the structural analysis of ordered beta-aggregation is presented and validated on three known amyloidogenic polypeptides. The strategy is based on the decomposition of the sequence into overlapping stretches and equilibrium implicit solvent molecular dynamics (MD) simulations of an oligomeric system for each stretch. The structural stability of the in-register parallel aggregates sampled in the implicit solvent runs is further evaluated using explicit water simulations for a subset of the stretches. The beta-aggregation propensity along the sequence of the Alzheimer's amyloid-beta peptide (Abeta(42)) is found to be highly heterogeneous with a maximum in the segment V(12)HHQKLVFFAE(22) and minima at S(8)G(9), G(25)S(26), G(29)A(30), and G(38)V(39), which are turn-like segments. The simulation results suggest that these sites may play a crucial role in determining the aggregation tendency and the fibrillar structure of Abeta(42). Similar findings are obtained for the human amylin, a 37-residue peptide that displays a maximal beta-aggregation propensity at Q(10)RLANFLVHSSNN(22) and two turn-like sites at G(24)A(25) and G(33)S(34). In the third application, the MD approach is used to identify beta-aggregation "hot-spots" within the N-terminal domain of the yeast prion Ure2p (Ure2p(1-94)) and to design a double-point mutant (Ure2p-N4748S(1-94)) with lower beta-aggregation propensity. The change in the aggregation propensity of Ure2p-N4748S(1-94) is verified in vitro using the thioflavin T binding assay.

Amino Acid Sequence↗

Workers' safety in milking premises.

Dairy cattle rearing techniques have evolved, and milking has moved from stalls to specialized premises. A survey was carried out on a representative sample of dairy farms in central Italy to investigate workers' safety in milking premises. Results indicated acceptable sound level and microclimatic conditions, whereas repetitive motion of the upper limbs should be carefully monitored for the possible effects it can induce on the milkers, who were devoid of adequate personal protective equipment (PPE). Floor antislipping characteristics represented a major deficiency in the building material, in spite of its strength and durability.

Adult↗

Replica exchange molecular dynamics simulations of amyloid peptide aggregation.

The replica exchange molecular dynamics (REMD) approach is applied to four oligomeric peptide systems. At physiologically relevant temperature values REMD samples conformation space and aggregation transitions more efficiently than constant temperature molecular dynamics (CTMD). During the aggregation process the energetic and structural properties are essentially the same in REMD and CTMD. A condensation stage toward disordered aggregates precedes the beta-sheet formation. Two order parameters, borrowed from anisotropic fluid analysis, are used to monitor the aggregation process. The order parameters do not depend on the peptide sequence and length and therefore allow to compare the amyloidogenic propensity of different peptides

Amyloid↗

Two genetically related strains of Tuber borchii produce Tilia mycorrhizas with different morphological traits.

Two genetically related strains of Tuber borchii Vittad. (1BO and 43BO) produce mycorrhizas with Tilia platyphyllos Scop. with a different degree of efficiency. The aim of this work was to characterize the morphology of the fungal symbiotic structures in order to examine potential relationships between the anatomical traits of the mycorrhiza, the mycorrhizal capacities of the fungal strains and their effect on the host plants. Some morphological features of mantle hyphae (small size, intense staining, vacuolization, abundance of mitochondria) led to a mantle with morphological features that were isolate-specific. There were unexpected differences, at least under our experimental conditions: 1BO strain mantle cells were larger, less reactive to staining, more highly vacuolated and poorer in mitochondria than those of 43BO. These features were found throughout the mantle in 1BO, while the inner mantle hyphae of 43BO were significantly smaller and more intensely stained than the outer cells. In the 43BO strain there was a positive relation between these features and higher infectivity (evaluated as percentage of mycorrhizal tips) as well as a slightly more effective stimulation of plant growth. These observations suggest that genetically related truffle strains produce mycorrhizas with different morphologies, which may be related to a more efficient response of the host plant to inoculation.

Ascomycota↗

Comparative study and molecular characterization of ectomycorrhizas in Tilia americana and Quercus pubescens with Tuber brumale.

Mycorrhizas of Tuber brumale on Quercus pubescens and Tilia americana were obtained in vitro using micropropagated plantlets. Mycelium pure cultures were used for inoculation. Both the mycelium used for the inoculations, as well as the mycorrhizas which were obtained, were identified using several molecular approaches: analysis of the ITS region, polymerase chain reaction (PCR) specific primers and sequencing. The mycorrhizas were described from a morphological standpoint. Some of their biometric characteristics were different in bass-wood than they were in oak, thus showing the influence of the host plant on several of the morphological features believed to be necessary for the identification of the species. Considering the variability of their morphological characteristics, molecular analysis proved to be a necessary tool for the recognition of the mycorrhizas of Tuber spp.

Ascomycota↗

Heavy metals in atmospheric surrogate dry deposition

This paper describes a methodological approach for the assessment of the amount of surrogate dry deposition of several toxic heavy metals (Cd, Cr, Cu, Ni, Pb, V, Zn) associated with atmospheric particulate matter at ground level. The objectives of the study were twofold: i) the evaluation of several techniques for the digestion of dry deposition samples for trace metal analysis; ii) the comparison of the results from two samplers with different collecting surfaces. A dry solid surface sampler (DRY sampler, Andersen--USA) and a water layer surface sampler (DAS sampler--MTX Italy) were employed. The samples were collected over a one-year period in an urban site of Bologna (northern Italy). A description is given of the complete procedure, from sampling to data elaboration, including sample storage, digestion and analytical methods. According to the results obtained with three different digestion techniques (Teflon bomb, microwave digester and Teflon flask with vapour cooling system), the highest recovery rate was achieved by the Teflon bomb procedure employing an NBS 1648 Standard Reference Material; 90-95% of the elements considered were recovered by dissolution in a pressurized Teflon bomb with an HNO3-HF mixture. Given these results, the technique was adopted for dry deposition sample digestion. On the basis of the amount of heavy metals measured as monthly deposition fluxes (microg/m2), the collecting efficiency of the DAS sampler for a number of elements was found to be as much as two to three times greater than that of the DRY sampler.

Journal Article↗

Natural-killer-stimulatory effect of combined low-dose interleukin-2 and interferon beta in hairy-cell leukemia patients.

The association of low doses of interleukin-2 (IL-2; 5 IU/ml) and interferon beta (IFN beta; 10 IU/ml) induced an additive or synergic stimulatory effect on natural killer (NK) activity (32%) in peripheral blood samples from hairy-cell leukemia patients, both those with active disease and those in remission. The synergic NK stimulatory effect was more commonly found in samples from patients with active disease, while the additive effect was more frequent in the patients in remission. The IL-2/IFN beta combination provoked a nonadditive nonsynergic NK-stimulatory effect in a further 19.8% samples. The targets of the IL-2/IFN beta combination were typical NK cells, as shown by the fact that there was increased cytotoxicity (synergic, additive or nonadditive nonsynergic) against the K562, but not the Daudi cell line in peripheral blood mononuclear cell samples treated with the combination of the two cytokines. When CD16+/CD56+ or CD57+/CD16+/CD56+ cells were removed, the NK-stimulatory effect was lost. The fact that the NK-cell-enhancing activity of the IL-2/IFN beta combination was reduced when Percoll fractions 2 and 3 were used, but still persisted in 66% of tests, may have been due to cytotoxicity being higher in the untreated fractions 2 and 3 than in the untreated unfractionated samples. One of the factors responsible for the NK-stimulatory effect appears to be the capacity of the IL-2/IFN beta combination to trigger an increase in IFN gamma synthesis. If similar experiments give like results in samples from patients suffering from other B-cell lymphoproliferative, or HIV-associated disorders, all of which are characterized by a deficiency in NK activity, it should be possible to use low-dose IL-2/IFN beta to treat these disorders and, perhaps, residual neoplastic disease without exposing the patient to undue toxicity. Further, by testing other combinations one should be able to identify the lowest IL-2 and IFN beta doses that would effectively boost the additive or synergic effect in a greater number of cases.

Antigens, CD↗

Double-blind randomized phase I study on the clinical tolerance and pharmacodynamics of natural and recombinant interferon-beta given intravenously.

The clinical tolerance and biological properties of 6 x 10(6) IU of Chinese hamster glycosylated recombinant interferon-beta (rHuIFN-beta) and natural IFN-beta (Frone) given i.v. were compared in 12 healthy volunteers in a randomized cross-over, double-blind trial. All subjects received a single injection of each type of IFN-beta. Both were well tolerated and provoked similar changes in clinical indices. Serum neopterin (Np) values increased significantly from the 24th to 72nd h post-injection of rHuIFN-beta and Frone. beta 2-Microglobulin (beta 2-M) serum levels were statistically above baseline 24-96 h after rHuIFN-beta, and from the 24th to the 120th h with Frone. Both IFNs provoked a rise in intracellular 2',5'-adenylate (2-5A) levels from the 10th to the 48th h, as well as in Hu-Mx synthesis, which was significant from the 10th to the 96th h. Serum levels of 2-5A, interleukin-1 alpha (IL-1 alpha), and interleukin-1 beta (IL-1 beta) remained unchanged. There were no statistical differences in the changes provoked by the two differently derived IFN-beta in any of the biological parameters studied. Overall, the results of this study indicate that rHuIFN-beta and Frone have similar pharmacodynamics.

2',5'-Oligoadenylate Synthetase↗

Granulocyte colony-stimulating factor crosses the placenta and stimulates fetal rat granulopoiesis.

We studied the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration to pregnant rats upon fetal and neonatal myelopoiesis. Pregnant rats were treated with rhG-CSF twice daily for 2, 4, and 6 days before parturition. rhG-CSF crossed the placenta and reached peak fetal serum concentrations 4 hours after administration. Peak fetal serum levels were 1,000-fold lower than levels detected in the dam. Hematopoietic effects of rhG-CSF were assessed by cytologic analysis of the newborn blood, spleen, bone marrow, thymus, and liver. White blood cell counts were increased twofold to fourfold in newborns. This increase was due to circulating numbers of polymorphonuclear cells (PMN). rhG-CSF induced a myeloid hyperplasia in the newborn marrow consisting of immature and mature myeloid cells in the day-2 and day-4 treated pups. Bone marrow of pups treated for 6 days contained mostly hyper-segmented PMN with little or no increase in myeloid precursors. An increase in the number of postmitotic (PMN, bands, and metamyelocytes) and mitotic (promyeloblasts, myeloblasts, and metamyeloblasts) myeloid cells in the spleen of neonates was observed. No change was detected in splenic lymphocytes or monocytes. No effect of rhG-CSF was noted in the newborn liver or thymus. These results demonstrate that maternally administered rhG-CSF crosses the placenta and specifically induces bone marrow and spleen myelopoiesis in the fetus and neonate. The significant myelopoietic effects of rhG-CSF at low concentrations in the fetus suggest an exquisite degree of developmental sensitivity to this cytokine and may provide enhanced defense mechanisms to the neonate.

Animals↗

Use of a biological extract of Serratia marcescens to decrease doxorubicin-induced myelosuppression in dogs.

Fifteen dogs were given doxorubicin, IV, at a dosage of 30 mg/m2 of body surface. A commercially available biological extract of Serratia marcescens (BESM) was administered SC to 9 of these dogs (0.04 mg/kg of body weight every third day, n = 2; 0.08 mg/kg every other day, n = 2; and 0.08 mg/kg daily, n = 5), beginning the day after administration of doxorubicin, in an attempt to find an optimal dosage and schedule of administration of BESM to reduce the duration and severity of chemotherapy-induced myelosuppression. Nine additional dogs were randomized into 3 groups of 3 dogs to receive 1 of the following dosages of BESM SC: 0.08, 0.16, and 0.32 mg/kg. Serum was harvested immediately prior to treatment and at 2, 4, 6, 8, 12, 24, 48, and 72 hours from this latter group of dogs for subsequent analysis of canine granulocyte colony-stimulating factor (G-CSF) by enzyme immunoassay. Increasing the dosage and schedule of administration of BESM reduced the duration and severity of doxorubicin-induced myelosuppression. Neutrophil counts of the group of dogs given BESM daily at a dosage of 0.08 mg/kg and the controls were evaluated statistically. The neutrophil count increased significantly (P < 0.05) above pretreatment values in BESM-treated dogs after day 7. Median neutrophil counts of the BESM-treated dogs were never significantly lower than pretreatment values, whereas the median counts of the dogs treated with doxorubicin alone were significantly below normal for 6 days (days 7-12).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[An echographic study of left ventricular function in acute myocardial infarct undergoing thrombolysis].

To evaluate the changes of left ventricular diastolic and systolic function and the timing of these changes in the early stages of acute myocardial infarction, serial echocardiograms were performed in 10 male patients (mean age of 56 years) with acute myocardial infarction, undergoing reperfusion by thrombolysis (recombinant tissue plasminogen activator). Echocardiograms were performed before reperfusion and 3, 6, 12, 24, 48, 72 hours, 7 and 14 days after thrombolysis. Significant differences of heart rate, systolic and diastolic blood pressure, left ventricular end diastolic volume, end-systolic volume and ejection fraction were not found. The mean regional wall motion index improved from 1.02 +/- 0.50 to 0.89 +/- 0.51 (p less than 0.05) at 48 hours; to 0.79 +/- 0.46 (p less than 0.01) at 72 hours; to 0.69 +/- 0.43 (p less than 0.001) at 7 days and to 0.61 +/- 0.40 at 14 days (p less than 0.001). The deceleration time decreased from 223 +/- 33 to 169 +/- 30 ms (p less than 0.001) 24 hours after reperfusion without further improvement. E peak velocity and E/A ratio significantly increased at 72 hours, while A peak velocity was not statistically different. A slow and progressive recovery of left ventricular function occurred after thrombolysis in acute myocardial infarction. Left ventricular diastole improves earlier while regional systolic function improves slowly till the hospital discharge.

Aged↗

Production of hemopoietic growth factors by bone tissue and bone cells in culture.

This study was carried out to determine whether bone might be a source of hemopoietic growth factors. Both neonatal murine calvaria and primary cultures of cells isolated from calvaria released, upon stimulation with lipopolysaccharide, an activity that stimulated the growth of the interleukin (IL) 3-dependent cell lines, 32D cl, 123, and NSF 60. Upon gel filtration, this activity eluted with a molecular weight of 30,000 kDa. Further characterization, however, revealed that the major activity in conditioned medium was not IL 3. Activity was absorbed by DEAE-Sephacel at low salt concentration, whereas IL 3 does not adhere. Furthermore, an IL 3-specific antiserum did not neutralize the activity from cells and only partly neutralized the activity generated by whole calvaria. After gel filtration, the 30-kDa activity stimulated the growth of very large colonies in semisolid medium consisting mainly of granulocytes with the remainder being macrophages. No colony types belonging to other hemopoietic lineages were found, indicating, again, that the activity was not identical to IL 3. Subsequently, conditioned medium was fractionated by hydrophobic chromatography on Phenyl-Sepharose CL-4B, yielding two peaks of activity. Neutralization of activity with antisera to granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL 3 and use of colony assays showed that medium conditioned by whole calvaria contained GM-CSF and granulocyte CSF (G-CSF) in similar amounts together with a little IL 3, and medium conditioned with calvaria cells contained GM-CSF and little G-CSF. We conclude that bone releases hemopoietic growth factors that could contribute both to hemopoiesis and to the recruitment of osteoclasts from progenitors resident in the adjacent marrow.

Animals↗

Non-invasive measurement of internal diameter of peripheral arteries during the cardiac cycle.

An ultrasonic device was developed for continuous monitoring of the internal diameter of human peripheral arteries. The diastolic internal diameter of the radial artery measured in 10 supine normotensive subjects averaged 2.36 +/- 0.12 mm (mean +/- s.e.) and the change in diameter during the pulse wave was 0.037 +/- 0.003 mm. It was surprising to find that when the transducer was used to apply pressure on the radial artery, the difference between the systolic and the diastolic diameter was significantly increased while the diastolic diameter was reduced. This method therefore allows continuous, accurate and non-invasive measurement of the internal diameter of the human radial artery.

Arteries↗

Murine osteoblastlike cells and the osteogenic cell MC3T3-E1 release a macrophage colony-stimulating activity in culture.

The osteoclast may be of hematopoietic lineage and as such its development could be regulated by colony-stimulating factors. Since there is much interest as to whether osteoblasts influence bone resorption, we examined whether bone cells produce colony-stimulating activity. Both cells isolated from neonatal calvaria and the osteogenic cell MC3T3-E1 were found to constitutively release a colony-stimulating activity possessing characteristics of a macrophage colony-stimulating factor, as determined by basic biochemical purification and by identity of colonies induced in cultures of bone marrow cells. Release could be increased by the presence of the bone-resorbing agents lipopolysaccharide and 1,25 dihydroxyvitamin D3. We conclude that the osteoblast may contribute to both the processes of osteoclast formation and of hematopoiesis through the secretion of colony-stimulating activity into the adjacent bone marrow.

Animals↗

A model of a single comprehensive mental health service for a catchment area: a community alternative to hospitalization.

The possibility of overcoming the Psychiatric Hospital with a single Community Service consisting of a network of territorial activities for the total population of a defined area is described. An evaluation is made from 1971 to 1983. Handicapped children are treated essentially in the family and normal educational structures. Diagnostic prevalence of more serious cases, modes of treatment, scholastic facilities and rejection of special schools are described. Work methods and community facilities, mean-year incidence and one-year prevalence of patients aged 15 + are examined. The latter convalidates priority towards serious risk situations. Specific rehabilitation and work-reintegration are programmed for handicap and disability patients. Release of long-stay psychiatric patients continues through alternative programmes with housing facilities. By 1985 the Psychiatric Hospital should close down. The population is treated by the C.M.H.S. when hospitalized in the General Hospital where no psychiatric ward exists. Crisis intervention, alternative treatment and hospitalization statistics are described.

Adolescent↗