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Biomedical subjects

M Rossi

Publications and source records attributed to M Rossi.

At least 109 records · Page 6Linked to original sources
PubMed2001

Heterocycle-containing retinoids. Discovery of a novel isoxazole arotinoid possessing potent apoptotic activity in multidrug and drug-induced apoptosis-resistant cells.

In a search for retinoic acid (RA) receptor ligands endowed with potent apoptotic activity, a series of novel arotinoids were prepared. Because the stereochemistry of the C9-alkenyl portion of natural 9-cis-RA and the olefinic moiety of the previously synthesized isoxazole retinoid 4 seems to have particular importance for their apoptotic activity, novel retinoid analogues with a restricted or, vice versa, a larger flexibility in this region were designed and prepared. The new compounds were evaluated in vitro for their ability to activate natural retinoid receptors and for their differentiation-inducing activity. Cytotoxic and apoptotic activities were, in addition, evaluated. In general, these analogues showed low cytotoxicity, with the restricted structures being slightly more active than the more flexible ones. As an exception, however, the isoxazole retinoid 15b proved to be particularly able to induce apoptosis at concentrations <5 microM, showing a higher activity than the classical retinoids such as all-trans-RA, 13-cis-RA, and 9-cis-RA and the previously described synthetic retinoid 4. 15b also exhibited a good affinity for the retinoid receptors. Interestingly, another important property of 15b was its ability to induce apoptosis in the HL60R multidrug-resistant (MDR) cell line, at the same concentration as is effective in HL60. Therefore, 15b represents a new retinoid possessing high apoptotic activity in an MDR cell line. The ability of 15b to act on K562 and HL60R cells suggests that this compound may have important implications in the treatment of different leukemias, and its structure could offer an interesting model for the design of new compounds endowed with apoptotic activity on MDR- and retinoid-resistant malignancies.

Antineoplastic Agents↗
PubMed2001

Suicidal poisoning with barium chloride.

A 49-year-old male pharmacist suffering from depression phoned the emergency services telling of how he had ingested barium chloride. He was found semicomatose in bed and resuscitation attempts were to no avail and he died at the scene. A white plastic container labelled "Barium chloride... Poison", and a book with a writing on a blank page... "give sulphate... SO(4)" were found. At autopsy, 1l of whitish-yellow fluid was found in the stomach. Autopsy barium levels were: blood 9.9mg/l; bile 8.8mg/l; urine 6.3mg/l; gastric 10.0g/l. Cause of death was given as cardiorespiratory arrest due to barium chloride poisoning. The issue of barium toxicity in a variety of itatrogenic and non itatrogenic situation is discussed together with the two only other cases of suicidal barium ingestion, and the feasibility of early intervention at the scene by an emergency team.

Autopsy↗
PubMed2001

Variant Creutzfeldt-Jakob disease in an elderly patient.

We report a case of variant Creutzfeldt-Jakob disease(vCJD) in a 74-year old man in whom diagnosis was made at necropsy. The occurrence of vCJD in an individual in this age group is unlikely to be an isolated event. Doctors need to be aware that vCJD can arise in elderly patients so that appropriate investigations (including magnetic resonance imaging) can be done, and permission for neuropathological necropsy requested, in suspected cases. This case could also have important implications for public health policy decisions and surveillance programmes that target the younger age range of vCJD cases.

Aged↗
PubMed2001

Effects of two-carbon bridge region methoxylation of benztropine: discovery of novel chiral ligands for the dopamine transporter.

6-Methoxylated and 8-oxygenated benztropines were prepared and evaluated for their DAT and SERT activity (binding and uptake inhibition). Methoxylation at the two-carbon bridge of benztropine produced a novel class of potent and selective DAT ligands. An interesting enantioselectivity was also observed for this new class of chiral benztropines. The inactivity of the 8-oxygenated analogues seems to point out that, unlike cocaine and its analogues, interactions of benztropine ligands with DAT may be strongly governed by the nitrogen atom.

Benztropine↗
PubMed2001

Pseudospectral approach to inverse problems in interface dynamics.

An improved scheme for computing coupling parameters of the Kardar-Parisi-Zhang equation from a collection of successive interface profiles is presented. The approach hinges on a spectral representation of this equation. An appropriate discretization based on a Fourier representation is discussed as a by-product of the above scheme. Our method is first tested on profiles generated by a one-dimensional Kardar-Parisi-Zhang equation, where it is shown to reproduce the input parameters very accurately. When applied to microscopic models of growth, it provides the values of the coupling parameters associated with the corresponding continuum equations. This technique compares favorably with previous methods based on real space schemes.

Journal Article↗
PubMed2001

Discontinuation of primary prophylaxis in HIV-infected patients at high risk of Pneumocystis carinii pneumonia: prospective multicentre study.

OBJECTIVES: To assess the safety of discontinuation of primary prophylaxis in HIV-infected patients on antiretroviral combination therapy at high risk of developing Pneumocystis carinii pneumonia. DESIGN: Prospective multicentre study. PATIENTS AND METHODS: The incidence of P. carinii pneumonia after discontinuation of primary prophylaxis was studied in 396 HIV-infected patients on antiretroviral combination therapy who experienced an increase in their CD4 cell count to at least 200 x 10(6)/l and 14% of total lymphocytes; the study population included 191 patients with a history of CD4 cell counts below 100 x 10(6)/l (245 person-years) and 144 patients with plasma HIV RNA above 200 copies/ml (215 person-years). RESULTS: There was one case of Pneumocystis pneumonia, an incidence of 0.18 per 100 person-years [95% confidence interval (CI), 0.005--1.0 per 100 person-years]. No case was diagnosed in groups with low nadir CD4 cell counts (95% CI, 0--1.2 per 100 person-years) or detectable plasma HIV RNA (95% CI, 0--1.4 per 100 person-years). CONCLUSIONS: Discontinuation of primary prophylaxis against Pneumocystis pneumonia is safe in patients who have responded with a sustained increase in their CD4 cell count to antiretroviral combination therapy, irrespective of the CD4 cell count nadir and the viral load at the time of stopping prophylaxis.

Adult↗
PubMed2001

From p63 to p53 across p73.

Most genes are members of a family. It is generally believed that a gene family derives from an ancestral gene by duplication and divergence. The tumor suppressor p53 was a striking exception to this established rule. However, two new p53 homologs, p63 and p73, have recently been described [1-6]. At the sequence level, p63 and p73 are more similar to each other than each is to p53, suggesting the possibility that the ancestral gene is a gene resembling p63/p73, while p53 is phylogenetically younger [1,2].The complexity of the family has also been enriched by the alternatively spliced forms of p63 and p73, which give rise to a complex network of proteins involved in the control of cell proliferation, apoptosis and development [1,2,4,7-9]. In this review we will mainly focus on similarities and differences as well as relationships among p63, p73 and p53.

Animals↗
PubMed2001

Physical interaction with Yes-associated protein enhances p73 transcriptional activity.

Specific protein-protein interactions are involved in a large number of cellular processes and are mainly mediated by structurally and functionally defined domains. Here we report that the nuclear phosphoprotein p73 can engage in a physical association with the Yes-associated protein (YAP). This association occurs under physiological conditions as shown by reciprocal co-immunoprecipitation of complexes from lysates of P19 cells. The WW domain of YAP and the PPPPY motif of p73 are directly involved in the association. Furthermore, as required for ligands to group I WW domains, the terminal tyrosine (Y) of the PPPPY motif of p73 was shown to be essential for the association with YAP. Unlike p73alpha, p73beta, and p63alpha, which bind to YAP, the endogenous as well as exogenously expressed wild-type p53 (wt-p53) and the p73gamma isoform do not interact with YAP. Indeed, we documented that YAP interacts only with those members of the p53 family that have a well conserved PPXY motif, a target sequence for WW domains. Overexpression of YAP causes an increase of p73alpha transcriptional activity. Differential interaction of YAP with members of the p53 family may provide a molecular explanation for their functional divergence in signaling.

Adaptor Proteins, Signal Transducing↗
PubMed2001

A novel member of the bacterial-archaeal regulator family is a nonspecific dna-binding protein and induces positive supercoiling.

In hyperthermophilic Archaea genomic DNA is from relaxed to positively supercoiled in vivo because of the action of the enzyme reverse gyrase, and this peculiarity is believed to be related to stabilization of DNA against denaturation. We report the identification and characterization of Smj12, a novel protein of Sulfolobus solfataricus, which is homologous to members of the so-called Bacterial-Archaeal family of regulators, found in multiple copies in Eubacteria and Archaea. Whereas other members of the family are sequence-specific DNA- binding proteins and have been implicated in transcriptional regulation, Smj12 is a nonspecific DNA-binding protein that stabilizes the double helix and induces positive supercoiling. Smj12 is not abundant, suggesting that it is not a general architectural protein, but rather has a specialized function and/or localization. Smj12 is the first protein with the described features identified in Archaea and might participate in control of superhelicity during DNA transactions.

Amino Acid Sequence↗
PubMed2001

Health risks posed by use of Di-2-ethylhexyl phthalate (DEHP) in PVC medical devices: a critical review.

BACKGROUND: Polyvinyl chloride plastics (PVC), made flexible through the addition of di-2-ethylhexyl phthalate (DEHP), are used in the production of a wide array of medical devices. From the late 1960s, leaching of DEHP from PVC medical devices and ultimate tissue deposition have been documented. METHODS: A critical review of DEHP exposure, metabolism, and toxicity data from human and animals studies was undertaken. A brief analysis of alternatives to DEHP-plasticized PVC for use in medical device manufacture was completed. RESULTS: DEHP leaches in varying concentrations into solutions stored in PVC medical devices. Certain populations, including dialysis patients and hemophiliacs may have long-term exposures to clinically important doses of DEHP, while others, such as neonates and the developing fetus, may have exposures at critical points in development. In vivo and in vitro research links DEHP or its metabolites to a range of adverse effects in the liver, reproductive tract, kidneys, lungs, and heart. Developing animals are particularly susceptible to effects on the reproductive system. Some adverse effects in animal studies occur at levels of exposure experienced by patients in certain clinical settings. DEHP appears to pose a relatively low risk of hepatic cancer in humans. However, given lingering uncertainties about the relevance of the mechanism of action of carcinogenic effects in rodents for humans and interindividual variability, the possibility of DEHP-related carcinogenic responses in humans cannot be ruled out. CONCLUSIONS: The observed toxicity of DEHP and availability of alternatives to many DEHP-containing PVC medical devices presents a compelling argument for moving assertively, but carefully, to the substitution of other materials for PVC in medical devices. The substitution of other materials for PVC would have an added worker and community health benefit of reducing population exposures to DEHP, reducing the creation of dioxin from PVC production and disposal, and reducing risks from vinyl chloride monomer exposure.

Animals↗
PubMed2001

Routine measurements of left and right ventricular output by gated blood pool emission tomography in comparison with thermodilution measurements: a preliminary study.

The aim of this preliminary study was to evaluate the accuracy of left and right ventricular output computed from a semi-automatic processing of tomographic radionuclide ventriculography data (TRVG) in comparison with the conventional thermodilution method. Twenty patients with various heart diseases were prospectively included in the study. Thermodilution and TRVG acquisitions were carried out on the same day for all patients. Analysis of gated blood pool slices was performed using a watershed-based segmentation algorithm. Right and left ventricular output measured by TRVG correlated well with the measurements obtained with thermodilution (r = 0.94 and 0.91 with SEE = 0.38 and 0.46 l/min, respectively, P < 0.001). The limits of agreement for TRVG and thermodilution measurements were -0.78-1.20 l/min for the left ventricle and -0.34-1.16 l/min for the right ventricle. No significant difference was found between the results of TRVG and thermodilution with respect to left ventricular output (P = 0.09). A small but significant difference was found between right ventricular output measured by TRVG and both left ventricular output measured by TRVG (mean difference = 0.17 l/min, P = 0.04) and thermodilution-derived cardiac output (mean difference = 0.41 l/min, P = 0.0001). It is concluded that the watershed-based semi-automatic segmentation of TRVG slices provides non-invasive measurements of right and left ventricular output and stroke volumes at equilibrium, in routine clinical settings. Further studies are necessary to check whether the accuracy of these measurements is good enough to permit correct assessment of intracardiac shunts.

Adult↗
PubMed2001

Pediatric renal transplantation: anesthesia and perioperative complications.

The appropriate choice of anesthesia for patients (pts) undergoing renal transplantation (Ktx) requires minimal toxicity and accurate monitoring for pts at high risk for metabolic, cardiovascular, and respiratory perioperative complications. We evaluated the anesthetic management and postoperative follow-up in pediatric Ktx performed in the last 12 years in our institution. From 1988 to 1999, 75 ASA class II-III pts (45 males, 22 females) younger than 18 years scheduled for Ktx were studied: 49 received a graft from a cadaveric donor (CD) and 26 from a living donor (LD). All pts were treated with dialysis within 24 h before the procedure. Standard monitoring consisted of an electrocardiogram, central venous pressure, non-invasive arterial pressure, pulse oximetry, and inspiratory and expiratory gas analysis. If necessary, an arterial cannula and pediatric pulmonary catheter were introduced. Anesthesia was induced with sodium thiopental, propofol, halothane, or sevoflurane and maintained with isoflurane and/or fentanyl and droperidol in O2:N2O (FiO2 0.4%). As muscle relaxants atracurium or cisatracurium besilate were used, except in allergic pts, in whom vecuronium or rocuronium bromide was administered. Dopamine, 20% mannitol, and furosemide were used to increase diuresis. Continuous morphine and ketoralac infusions were used for postoperative pain relief. The surgical technique was the same in all cases. Complications and renal-function (RF) recovery were evaluated relating to CD and LD using the chi-square test; differences in mean anesthesia and surgical time were evaluated by Student's t-test; survival curves were calculated from the day of Ktx to death or last follow-up and estimated by the Kaplan-Meier method. Values of P below 0.05 were considered significant. Postoperative immunosuppressive therapy was based on cyclosporine together with other conventional drugs. Mean anesthesia time was 228 +/- 65 min. Mean kidney ischemia time for CD was 16.5 +/- 4 h. Four pts (3 CD, 1 LD) died within 72 h postoperatively: 3 due to cardiac failure and 1 to metabolic coma. Six pts showed cardiovascular and 3 had infective complications, all successfully treated. Three pts (2 CD, 1 LD) died within 2 to 12 months after, surgery; 10 (6 CD, 4 LD) had graft failure and are still alive on dialysis; 58 (38 CD, 20 LD) are alive in good health after a mean follow-up of 57.6 +/- 36.6 months (range 12-120 months). Fifteen of 26 pts younger than 12 years (21 CD and 5 LD) recovered RF intraoperatively (10 CD, 5 LD); 1 with CD and 1 with LD showed postoperative graft failure and 2 with CD died within 72 h postoperatively, 22 (18 CD and 4 LD) are alive in good health. This group showed no statistical difference compared to pts older than 12 years. Of 16 pts (15 CD and 1 LD) with body weight (BW) less than 25 kg, 6 showed intraoperative (5 CD, 1 LD) recovery of RF. The 3 deaths were all in CD pts, 2 within 72 h and one 2 months after surgery; only 1 LD had postoperative graft failure. Twelve pts (75%) (12 CD, 80%) are alive in good health. Compared to pts with BW of 25 kg or more, this group showed lower intraoperative recovery of RF (P < or = 0.05). No peri- and postoperative complications occurred in all 26 LD pts (100%). Recent advances in surgery, anesthesia, immunosuppression, and antimicrobial prophylaxis have made Ktx a more predictable procedure even in pediatric pts. For high-risk pts, mortality and morbidity can be controlled by accurate surgical, anesthetic, and postoperative management. Pts younger than 12 years and with BW less than 25 kg are more likely to develop peri- and postoperative complications.

Adolescent↗
PubMed2001

Enzymatic synthesis of oligosaccharides by two glycosyl hydrolases of Sulfolobus solfataricus.

The importance of carbohydrates in a variety of biological functions is the reason that interest has recently increased in these compounds as possible components of therapeutic agents. Thus, the need for a technique allowing the easy synthesis of carbohydrates and glucoconjugates is an emerging challenge for chemists and biologists involved in this field. At present, enzymatic synthesis has resulted in the most promising approach for the production of complex oligosaccharides. In this respect, the enzymological characteristics of the catalysts, in term of regioselectivity, substrate specificity, and operational stability, are of fundamental importance to improve the yields of the process and to widen the repertoire of the available products. Here, two methods of oligosaccharide synthesis performed by a glycosynthase and by an alpha-xylosidase from the hyperthermophilic archaeon Sulfolobus solfataricus are briefly reviewed. The approaches used and the biodiversity of the catalysts together are key features for their possible utilization in the synthesis of oligosaccharides.

Carbohydrate Conformation↗
PubMed2001

Thermoadaptation of a mesophilic hygromycin B phosphotransferase by directed evolution in hyperthermophilic Archaea: selection of a stable genetic marker for DNA transfer into Sulfolobus solfataricus.

A mutated version of the hygromycin B phosphotransferase (hph(mut)) gene from Escherichia coli, isolated by directed evolution at 75 degrees C in transformants of a thermophilic strain of Sulfolobus solfataricus, was characterized with respect to its genetic stability in both the original mesophilic and the new thermophilic hosts. This gene was demonstrated to be able to express the hygromycin B resistance phenotype and to be steadily maintained and propagated also in other, more thermophilic strains of S. solfataricus, i.e., up to 82 degrees C. Furthermore, it may be transferred to S. solfataricus cells by cotransformation with pKMSD48, another extrachromosomal element derived from the virus SSV1 of Sulfolobus shibatae, without any loss of stability and without affecting the replication and infectivity of this viral DNA. The hph(mut) and the wild-type gene products were expressed at higher levels in E. coli and purified by specific affinity chromatography on immobilized hygromycin B. Comparative characterization revealed that the mutant enzyme had acquired significant thermoresistance and displayed higher thermal activity with augmented catalytic efficiency.

Adaptation, Biological↗
PubMed2001

Identification and molecular characterization of an endoglucanase gene, celS, from the extremely thermophilic archaeon Sulfolobus solfataricus.

A genomic region upstream of the alcohol dehydrogenase (Ssadh) gene was cloned and sequenced from a library of Sulfolobus solfataricus MT4 strain. The isolated 4,040-bp DNA fragment revealed an open reading frame (celS), lying in the opposite direction to Ssadh, which showed significant similarity to endo-beta-1,4-glucanases from Pyrococcus furiosus, Thermotoga maritima, and Thermotoga neapolitana. celS was shown to be a functional gene in vivo: a specific celS mRNA was detected by primer extension analysis showing a unique initiation transcription site coinciding with the ATG translation initiation codon. The specific gene product was detected as an extracellular cellulase after enzyme staining by carboxymethyl cellulose (CMC) SDS-PAGE, showing a molecular weight in agreement with that deduced from the open reading frame. Depending on growth conditions, different levels of cellulase activity and specific celS transcript were detected, revealing an inductive effect of CMC and suggesting a repressive role of glucose.

Amino Acid Sequence↗
PubMed2001

Enzymatic synthesis and hydrolysis of xylogluco-oligosaccharides using the first archaeal alpha-xylosidase from Sulfolobus solfataricus.

The first, recently identified, archaeal alpha-xylosidase from Sulfolobus solfataricus (XylS) shows high specificity for hydrolysis of isoprimeverose [alpha-D-xylopyranosyl-(1,6)-D-glucopyranose, (X)], the p-nitrophenyl-beta derivative of isoprimeverose, and xyloglucan oligosaccharides and has transxylosidic activity, forming, in a retaining mode, interesting alpha-xylosides. This article describes the synthesis of isoprimeverose, the disaccharidic repeating unit of xyloglucan, of the p-nitrophenyl-beta derivative of isoprimeverose, and of a trisaccharide based on isoprimeverose that is one of the trisaccharidic building blocks of xyloglucan. A substrate structure-activity relationship is recognized for both the hydrolysis and the synthesis reactions of XylS, it being a biocatalyst (i) active hydrolytically only on X-ending substrates liberating a xylose molecule and (ii) capable of transferring xylose only on the nonreducing end glucose of p-nitrophenyl-(PNP)-beta-D-cellobioside. The compounds synthesized by this enzyme are a starting point for enzymological studies of other new enzymes (i.e., xyloglucanases) for which suitable substrates are difficult to synthesize. This study also allows us to define the chemical characteristics of the xylose-transferring activity of this new archaeal enzyme, contributing to building up a library of different glycosidases with high specific selectivity for oligosaccharide synthesis.

Archaeal Proteins↗
PubMed2001

Passive limb movements improve visual neglect.

Recent studies have reported that left neglect can be ameliorated during active movements of a contralesional limb in the contralesional space. In contrast, a passive left hand movement does not seem to induce an amelioration of neglect, at least when it is associated to simultaneous active right movement (Robertson IH, North N, Neuropsychologia 31 (1993) 293-300). In the present study, we explored the possibility that a complex passive movement, such as abduction and adduction of the arm, is able to reduce neglect also when it is associated to simultaneous active right arm movements. To test this hypothesis neglect patients were required to perform an object cancellation test and a line bisection test by using the right hand, while the left arm was passively moved. Moreover, we verified the possibility that left arm stimulation activates the peripersonal more than the extrapersonal space, with the exception of the condition in which the far space can be reached by a tool that extends peripersonal space in the far space (Farnè A, Làdavas E, Neuroreport 11 (2000) 1645-1649). For this reason, patients were required to perform the tasks in near (70 cm) and in far (140 cm) space by means of a light pen (pointing task) and of a stick (reaching task). When the left arm was passively moved the results showed a significant reduction of neglect with respect to the baseline condition, and the improvement equally affected the near and the far space. A different effect for the near and far space was observed in relation to the task (pointing vs. reaching). In the pointing task, neglect was more severe in the far than in near space; however, this difference disappeared when the patients had to reach objects by means of a stick. In conclusion, the present study shows that the entity of improvement of visual neglect due to a left passive movement is related to the entity of proprioceptive signals specifying left hand position.

Aged↗