Search PubMed⌕ Search

Biomedical subjects

M Molinari

Publications and source records attributed to M Molinari.

At least 19 recordsLinked to original sources
PubMed2001

Palliative strategies for locally advanced unresectable and metastatic pancreatic cancer.

Technical improvement in perioperative morbidity and mortality with improved long-term survival associated with pancreaticoduodenectomy for patients with pancreatic carcinoma has clearly established a role for this operation when performed with curative intent. Most patients with pancreatic adenocarcinoma will not be candidates for surgical resection of their disease. These patients will experience significant symptoms potentially requiring surgical and nonsurgical palliative interventions to treat unrelieved cancer-associated pain, obstructive jaundice, or the development of GOO. The primary goal for palliative interventions should be to relieve symptoms with minimal morbidity and to maintain or improve the quality of life for patients with an expected limited survival.

Adenocarcinoma↗
PubMed2001

Adaptive mesh refinement techniques for electrical impedance tomography.

Adaptive mesh refinement techniques can be applied to increase the efficiency of electrical impedance tomography reconstruction algorithms by reducing computational and storage cost as well as providing problem-dependent solution structures. A self-adaptive refinement algorithm based on an a posteriori error estimate has been developed and its results are shown in comparison with uniform mesh refinement for a simple head model.

Algorithms↗
PubMed2001

Functional changes of the primary somatosensory cortex in patients with unilateral cerebellar lesions.

Although cerebellar lesions do not cause evident sensory deficits, it has been suggested recently that the cerebellum might play a role in sensory acquisition and discrimination. To determine whether the cerebellum influences the early phases of cortical somatosensory processing, we recorded cortical somatosensory evoked potentials after median nerve stimulation in five patients with unilateral cerebellar damage. We also performed a dipolar source analysis of traces by means of brain electrical source analysis. In all patients, the amplitude of the frontal N24 and parietal P24 components, as well as the strength of the corresponding dipolar sources, were significantly smaller after stimulation of the symptomatic side. These neurophysiological findings indicate that the primary somatosensory cortical processing is altered after contralateral cerebellar damage. They represent the first indication of a possible substrate for the reduction in cerebral blood flow observed in the parietal cortex after cerebellar lesion. Furthermore, the present data allow characterization of the functional influence of the cerebellar input to the primary somatosensory cortex as specifically acting over the inhibitory components of somatosensory processing.

Adult↗
PubMed2001

Eye-hand coordination during reaching. I. Anatomical relationships between parietal and frontal cortex.

The anatomical and physiological substrata of eye-hand coordination during reaching were studied through combined anatomical and physiological techniques. The association connections of parietal areas V6A and PEc, and those of dorso-rostral (F7) and dorso-caudal (F2) premotor cortex were studied in monkeys, after physiological characterization of the parietal regions where retrograde tracers were injected. The results show that parieto-occipital area V6A is reciprocally connected with F7, and receives a smaller projection from F2. Local parietal projections to V6A arise from areas MIP and, to a lesser extent, 7m, PEa and PEC: On the contrary, parietal area PEc is strongly and reciprocally connected with the part of F2 located close to the pre-central dimple (pre-CD). Local parietal projections to PEc come from a distributed network, including PEa, MIP, PEci and, to a lesser extent, 7m, V6A, 7a and MST. Premotor area F7 receives parietal projections mainly from 7m and V6A, and local frontal projections mainly from F2. On the contrary, premotor area F2 in the pre-CD zone receives parietal inputs from PEc and, to a lesser extent, PEci, while in the peri-arcuate zone F2 receives parietal projections from PEa and MIP. Local frontal projections to F2 pre-CD mostly stem from F4, and, to a lesser extent, from F7 and F3, and CMAd; those addressed to peri-arcuate zone of F2 arise mainly from F5 and, to a lesser extent, from F7, F4, dorsal (CMAd) and ventral (CMAv) cingulate motor areas, pre-supplementary (F6) and supplementary (F3) motor areas. The distribution of association cells in both frontal and parietal cortex was characterized through a spectral analysis that revealed an arrangement of these cells in the form of bands, composed of cell clusters, or 'columns'. The reciprocal connections linking parietal and frontal cortex might explain the presence of visually related and eye-position signals in premotor cortex, as well as the influence of information about arm position and movement direction in V6A and PEC: The association connections identified in this study might carry sensory as well motor information that presumably provides a basis for a re-entrant signaling. This might be necessary to match retinal-, eye- and hand-related information underlying eye-hand coordination during reaching.

Animals↗
PubMed2001

Eye-hand coordination during reaching. II. An analysis of the relationships between visuomanual signals in parietal cortex and parieto-frontal association projections.

The relationships between the distribution of visuomanual signals in parietal cortex and that of parieto-frontal projections are the subject of the present study. Single cell recording was performed in areas PEc and V6A, where different anatomical tracers were also injected. The monkeys performed a variety of behavioral tasks, aimed at studying the visual and motor properties of parietal cells, as well as the potential combination of retinal-, eye- and hand-related signals on cell activity. The activity of most cells was related to the direction of movement and the active position of the hand. Many of these reach-related cells were influenced by eye position information. Fewer cells displayed relationships to saccadic eye movements. The activity of most neurons related to a combination of both hand and eye signals. Many cells were also modulated during preparation for hand movement. Light-dark differences of activity were common and interpreted as related to the sight and monitoring of hand motion and/or position in the visual field. Most cells studied were very sensitive to moving visual stimuli and also responded to optic flow stimulation. Visual receptive fields were generally large and extended to the periphery of the visual field. For most neurons, the orientation of the preferred directions computed across different epochs and tasks conditions clustered within a limited sector of space, the field of global tuning. This can be regarded as an ideal frame to combine spatially congruent eye- and hand-related information for different forms of visuomanual behavior. All these properties were common to both PEc and V6A. Retinal, eye- and hand-related activity types, as well as parieto-frontal association cells, were distributed in a periodic fashion across the tangential domain of areas PEc and V6A. These functional and anatomical distributions were characterized and compared through a spectral and coherency analysis, which revealed the existence of a selective 'match' between activity types and parieto-frontal connections. This match depended on where each individual efferent projection was addressed. The results of the present and of the companion study can be relevant for a re-interpretation of optic ataxia as the consequence of the breakdown of the combination of retinal-, eye- and hand-related directional signals within the global tuning fields of parietal neurons.

Animals↗
PubMed2001

[Lung base disease after orthotopic liver transplantation. Functional ultrasonography of the diaphragm and correlated alterations].

PURPOSE: To demonstrate the greater accuracy of B- and M-probe ultrasound (US) compared to traditional examinations in the evaluation of diseases of the lung-base, a frequent localisation of pathology in patients undergoing orthotopic liver transplantation (OLT). MATERIAL AND METHODS: Twenty-one patients, 13 males and 8 females aged 24 to 63, awaiting OLT were examined using the three modalities. B-mode US was performed as a preliminary study to identify the districts of interest and the profile of the diaphragm wall, searching for any related alterations. This was followed by M-mode US, with an approach along the left and right posterior axillary lines during spontaneous and forced maximal expiration, to calculate and document the curve representing diaphragm mobility. All patients were also studied pre- and postoperatively by standard chest X-ray double projections. The parameters evaluated by US were diaphragmatic inspiratory slant and diaphragm range while the standard chest X-ray was used to assess hypoventilation, diaphragm range and pleural effusion. RESULTS: For each parameter considered we obtained the following results: presence or absence of pleural effusion (sensitivity: 100% with US vs 64% with chest X-ray) and diaphragmatic hypomobility with related hypoventilatory phenomena (sensitivity: 85% with US, with 15% false negatives). In 15 cases the chest X-ray revealed a clear elevation of the diaphragm, a finding supported by US in 11 cases. In 7 cases US showed a reduction in the diaphragm range curve without, however, any radiological evidence of any ventilatory dysfunction of the lung base and/or elevation of the corresponding hemidiaphragm. CONCLUSION: Our results suggest that radiology, B-mode US and color Doppler US, which are widely used for monitoring OLT patients, can be usefully integrated by M-mode US to evaluate diaphragmatic mobility both pre- and post-operatively. This method is fast, easy to use and widely available.

Adult↗
PubMed2000

Downregulation of 14-3-3sigma prevents clonal evolution and leads to immortalization of primary human keratinocytes.

In human epidermal keratinocytes, replicative senescence, is determined by a progressive decline of clonogenic and dividing cells. Its timing is controlled by clonal evolution, that is, by the continuous transition from stem cells to transient amplifying cells. We now report that downregulation of 14-3-3sigma, which is specifically expressed in human stratified epithelia, prevents keratinocyte clonal evolution, thereby forcing keratinocytes into the stem cell compartment. This allows primary human keratinocytes to readily escape replicative senescence. 14-3-3sigma-dependent bypass of senescence is accompanied by maintenance of telomerase activity and by downregulation of the p16(INK4a) tumor suppressor gene, hallmarks of keratinocyte immortalization. Taken together, these data therefore suggest that inhibition of a single endogenous gene product fosters immortalization of primary human epithelial cells without the need of exogenous oncogenes and/or oncoviruses.

14-3-3 Proteins↗
PubMed2000

Chaperone selection during glycoprotein translocation into the endoplasmic reticulum.

A variety of molecular chaperones and folding enzymes assist the folding of newly synthesized proteins in the endoplasmic reticulum. Here we investigated why some glycoproteins interact with the molecular chaperone BiP, and others with the calnexin/calreticulin pathway. The folding of Semliki forest virus glycoproteins and influenza hemagglutinin was studied in living cells. The initial choice of chaperone depended on the location of N-linked glycans in the growing nascent chain. Direct interaction with calnexin and calreticulin without prior interaction with BiP occurred if glycans were present within about 50 residues of the protein's NH2-terminus.

Animals↗
PubMed2000

Representation of actions in rats: the role of cerebellum in learning spatial performances by observation.

Experimental evidence demonstrates that cerebellar networks are involved in spatial learning, controlling the acquisition of exploration strategies without blocking motor execution of the task. Action learning by observation has been considered somehow related to motor physiology, because it provides a way of learning performances that is almost as effective as the actual execution of actions. Neuroimaging studies demonstrate that observation of movements performed by others, imagination of actions, and actual execution of motor performances share common neural substrates and that the cerebellum is among these shared areas. The present paper analyzes the effects of observation in learning a spatial task, focusing on the cerebellar role in learning a spatial ability through observation. We allowed normal rats to observe 200 Morris water maze trials performed by companion rats. After this observation training, "observer" rats underwent a hemicerebellectomy and then were tested in the Morris water maze. In spite of the cerebellar lesion, they displayed no spatial defects, exhibiting exploration abilities comparable to controls. When the cerebellar lesion preceded observation training, a complete lack of spatial observational learning was observed. Thus, as demonstrated already for the acquisition of spatial procedures through actual execution, cerebellar circuits appear to play a key role in the acquisition of spatial procedures also through observation. In conclusion, the present results provide strong support for a common neural basis in the observation of actions that are to be reproduced as well as in the actual production of the same actions.

Animals↗
PubMed2000

Pancreatic heterotopia and other uncommon causes of non-malignant biliary obstruction.

The vast majority of patients developing obstructive jaundice will have an underlying malignancy. When the etiology of the obstruction cannot be defined prior to operative intervention, identification of a non-malignant process will occur only subsequent to a major operation. The clinical course of a patient with complete distal common bile duct obstruction as the result of pancreatic heterotopia is discussed. This uncommon diagnosis prompted a review of the literature on this subject enabling this detailed discussion inclusive of the embryology, prevalence and clinical presentations of this entity. Our review further identified a varied group of other non-malignant causes of biliary obstruction that may be mistakenly interpreted to represent biliary or pancreatic malignancy.

Abdominal Pain↗
PubMed2000

Cell cycle checkpoints and their inactivation in human cancer.

Checkpoints are mechanisms that regulate progression through the cell cycle insuring that each step takes place only once and in the right sequence. Mutations of checkpoint proteins are frequent in all types of cancer as defects in cell cycle control can lead to genetic instability. This review will focus on three major areas of cell cycle transition control, with particular attention to the alterations found in human cancer. These areas include the G1/S transition, where most cancer-related defects occur, the G2/M checkpoint and its activation in response to DNA damage, and the spindle checkpoint.

G1 Phase↗
PubMed2000

Human Cdc25 A inactivation in response to S phase inhibition and its role in preventing premature mitosis.

The Cdc25 A phosphatase is required for the G1-S transition of the cell cycle and is overexpressed in human cancers. We found that it is ubiquitylated and rapidly degraded by the proteasome and that its levels increase from G1 until mitosis. By treating cells with the DNA synthesis inhibitor hydroxyurea, Cdc25 A rapidly decreased in abundance, and this was accompanied by an increase in Cdk2 phosphotyrosine content and a decrease in Cdk2 kinase activity. Cdc25 A overexpression altered the ability of cells to arrest in the presence of hydroxyurea, and caused them to undergo premature chromosome condensation. Cdc25 A overexpression could render tumor cells less sensitive to DNA replication checkpoints, thereby contributing to their genomic instability.

Bromodeoxyuridine↗
PubMed2000

Phonological grouping is specifically affected in cerebellar patients: a verbal fluency study.

OBJECTIVES: Recent clinical and functional neuroimaging evidence points towards a cerebellar role in verbal production. At present it is not clear how the cerebellum participates in language production. The aim was to investigate the influence of cerebellar lesions on verbal fluency abilities with specific focus on the verbal searching strategies employed by patients with cerebellar damage. METHODS: Twenty five patients with focal or degenerative cerebellar disease and 14 control subjects were tested in a timed verbal fluency task requiring word production under forced (phonemic or semantic) conditions. To analyse the verbal searching strategy employed, semantic and phonemic cluster analyses were also performed. RESULTS: Performances of cerebellar patients were comparable with those of controls in the semantic task; conversely their performances were significantly impaired when tested in the letter task. Cluster analysis results showed that the verbal fluency impairment is linked to specific damage of phonemically related retrieval strategies. CONCLUSION: Cerebellar damage impairs verbal fluency by specifically affecting phonemic rule performances while sparing semantic rule ones. These findings underline the importance of the cerebellar computing properties in strategy development in the linguistic domain.

Adult↗
PubMed2000

[Computerized tomography assessment of femoral and tibial rotation in total knee prosthesis].

PURPOSE: CT assessment of the axial deviation of the femoral and tibial prosthetic components in total knee arthroplasty. MATERIAL AND METHODS: January to July 1999, seventeen patients, 10 males and 7 females, mean age 66 years (standard deviation +/- 4) were examined after total knee arthroplasty. Exclusion criteria were prosthesis loosening and severe (equal or superior to 7 degrees) varus or valgus deviation. All patients were examined with knee radiography in the standing position completed by axial projections of patella and by CT scanning. We used a modification of Berger technique and carried out comparative CT scans extended lower limbs and acquisitions perpendicular to the mechanical axis of the knee, from the femoral supracondylar region down to the plane crossing the distal end of the tibial prosthetic component. Reference lines were then drawn electronically on given scanning planes to reckon the axial deviation of the femoral and tibial prosthetic components. RESULTS: Six patients, one female and 5 males, with normal rotational values of femoral and tibial prosthetic components presented no clinical symptoms. Eight patients, 4 females and 4 males, with abnormal values presented the following clinical symptoms: medial impingement, (incomplete) dislocation patella, and lateral instability. One female patient with a normal rotational value of femoral prosthetic component and an altered value of tibial prosthetic component presented medial impingement. Finally two patients, one female and one male, were absolutely asymptomatic although the rotational values of the two prosthetic components were beyond the normal range. CONCLUSIONS: Total knee arthroplasty is presently a standard treatment for many conditions involving this joint. There are several possible postoperative complications, namely fractures, dislocations (a)septic loosening and femoropatellar instability. The latter condition is the most frequent complication among implant failures and is caused by bad orientation of the femoral and tibial components on frontal and axial planes. We measured the orientation of the prosthetic components introducing a CT procedure which modifies the uniarticular with four scans introduced by Berger. The new method uses Berger's parameters and the CT study of both joints by means of Helical CT. With a single examination lasting less than 4 minutes and with the patient in a more comfortable position, we can obtain: 1) comparative and simultaneous assessment of the contralateral joint; 2) several scans to better define Berger's parameters and to accomplish measurement of the rotational deviation with higher precision and markedly decreasing the error margin. The analysis of the results confirms the international literature findings and especially the fundamental importance in positioning both prosthetic components within normal values, as emphasized by the relationship between the clinical symptoms and the rotational degree of the femoral and tibial prosthetic components.

Aged↗
PubMed1999

Setting the standards: quality control in the secretory pathway.

A variety of quality control mechanisms operate in the endoplasmic reticulum and in downstream compartments of the secretory pathway to ensure the fidelity and regulation of protein expression during cell life and differentiation. As a rule, only proteins that pass a stringent selection process are transported to their target organelles and compartments. If proper maturation fails, the aberrant products are degraded. Quality control improves folding efficiency by retaining proteins in the special folding environment of the endoplasmic reticulum, and it prevents harmful effects that could be caused by the deployment of incompletely folded or assembled proteins.

Animals↗
PubMed1999

Glycoproteins form mixed disulphides with oxidoreductases during folding in living cells.

The formation of intra- and interchain disulphide bonds constitutes an integral part of the maturation of most secretory and membrane-bound proteins in the endoplasmic reticulum. Evidence indicates that members of the protein disulphide isomerase (PDI) superfamily are part of the machinery needed for proper oxidation and isomerization of disulphide bonds. Models based on in vitro studies predict that the formation of mixed disulphide bonds between oxidoreductase and substrate is intermediate in the generation of the native intrachain disulphide bond in the substrate polypeptide. Whether this is how thiol oxidoreductases work inside the endoplasmic reticulum is not clear. Nor has it been established which of the many members of the PDI superfamily interacts directly with newly synthesized substrate proteins, because transient mixed disulphides have never been observed in the mammalian endoplasmic reticulum during oxidative protein folding. Here we describe the mechanisms involved in co- and post-translational protein oxidation in vivo. We show that the endoplasmic-reticulum-resident oxidoreductases PDI and ERp57 are directly involved in disulphide oxidation and isomerization, and, together with the lectins calnexin and calreticulin, are central in glycoprotein folding in the endoplasmic reticulum of mammalian cells.

Alkylating Agents↗
PubMed1999

Cerebellar contribution to spatial event processing: characterization of procedural learning.

Recently, we demonstrated the prevalent role of cerebellar networks in the acquisition of the procedural components of spatial information by testing hemicerebellectomized (HCbed) rats in a classical spatial task, the Morris water maze (MWM). As procedures used in the water maze are a mixture of different components (that is, general procedures, exploration procedures, direct reaching procedures), for optimally solving a spatial task all procedural components must be opportunely managed. Thus, severely impaired procedural learning of cerebellar origin can be better comprehended by fractionating the procedural facets. To this aim, a two-step water-maze paradigm was employed. Normal rats were first trained to search for a hidden platform moved to a different position in each trial, utilizing a water maze setting in which visual cues were abolished by heavy black curtains surrounding the tank. In this paradigm, normal animals solved the task by using general and exploration procedures, but they could not use direct reaching skills. A subgroup of these pretrained animals was then HCbed and, after recovery from cerebellar lesion, was tested in a water maze with normal environmental cues available, a paradigm in which normal animals develop abilities for reaching the target with very direct trajectories. Pretrained HCbed animals, however, did not display the typical spatial deficits of naive HCbed rats, persisted in exhibiting the scanning strategy learned during pretraining, and never displayed direct reaching skills. In conclusion, cerebellar networks appear to be involved in the acquisition of all procedural facets necessary for shifting behavior within the maze until direct reaching of the platform. The lack of flexibility in changing exploration strategies displayed by pretrained HCbed rats is interpreted by taking into account the well-known cerebellar frontal interplay sculpting a specific cerebellar role in the acquisition of spatial procedural steps.

Animals↗