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Biomedical subjects

A Berti

Publications and source records attributed to A Berti.

At least 19 recordsLinked to original sources
PubMed2000

When far becomes near: remapping of space by tool use.

Far (extrapersonal) and near (peripersonal) spaces are behaviorally defined as the space outside the hand-reaching distance and the space within the hand-reaching distance. Animal and human studies have confirmed this distinction, showing that space is not homogeneously represented in the brain. In this paper we demonstrate that the coding of space as "far" and "near" is not only determined by the hand-reaching distance, but it is also dependent on how the brain represents the extension of the body space. We will show that when the cerebral representation of body space is extended to include objects or tools used by the subject, space previously mapped as far can be remapped as near. Patient P.P., after a right hemisphere stroke, showed a dissociation between near and far spaces in the manifestation of neglect. Indeed, in a line bisection task, neglect was apparent in near space, but not in far space when bisection in the far space was performed with a projection lightpen. However, when in the far space bisection was performed with a stick, used by the patient to reach the line, neglect appeared and was as severe as neglect in the near space. An artificial extension of the patient's body (the stick) caused a remapping of far space as near space.

Aged↗
PubMed1999

Low M(r) phosphotyrosine protein phosphatase activity on fibroblast growth factor receptor is not associated with enzyme translocation.

Fibroblast growth factor receptor (class IV) shares a certain degree of similarity with class III members like platelet-derived growth factor and macrophage-colony-stimulating factor receptors, which, once activated, are substrates of low M(r) phosphotyrosine protein phosphatase. Up until now no phosphotyrosine phosphatase has been shown to act on this receptor in vivo. Here we demonstrate that low M(r) phosphotyrosine protein phosphatase is able to reduce receptor tyrosine phosphorylation and cell proliferation in response to basic fibroblast growth factor. Contrary to what was previously observed for platelet-derived growth factor, during cell stimulation with basic fibroblast growth factor, no enzyme redistribution among cellular compartments is observed.

3T3 Cells↗
PubMed1999

Somatosensory extinction for meaningful objects in a patient with right hemispheric stroke.

Implicit, high level processing of extinguished objects has often been described in the visual modality. In the tactile domain, however, research on this topic is meagre and it is still uncertain whether processing of tactually presented stimuli can be affected by the same attentional disorders as visual stimuli. In this paper we describe a patient, ENM, with visual neglect and light touch extinction who, in a naming task of objects presented in the tactile modality, simultaneously to both hands, showed extinction for left hand objects. He was, nevertheless, able to make above chance Same/Different judgements on the two stimuli. We also tested two neurologically intact subjects who performed the test wearing a ski-glove on the left hand to impair the recognition of left hand objects. In these subjects, Same/Different judgements were at chance level when recognition rate was as low as that found in patient ENM. This happened when either the objects, although sharing the same name were different in shape (conditions Same-Different) or when the two objects were different with respect to the category name but were actually physically similar (conditions Different-Similar). However, when the objects were either identical or completely different, i.e., in a condition where judgement could be based simply on the physical analysis of the object shape (condition Same Identical and Different Dissimilar), their Same/Different judgements were above chance, despite the tactual deficit. Our conclusion was that patient ENM showed implicit recognition of left hand objects, at least in the Same Different and in the Different-Similar conditions, whereas, in the same conditions, normal subjects with an artificial sensory impairment did not. Our results also show that Same/Different judgements may be, in some conditions, less demanding than naming tasks, as suggested by Farah et al. Furthermore, patient ENM performed the test both with uncrossed and crossed hands. We found that extinction always affected the hand contralateral to the brain damage, although there was a tendency for a decrement of the ipsilesional hand performance in the crossed condition. We discuss these findings with reference to the most recent theories on the existence of a body centered spatial frame of reference.

Aged↗
PubMed1998

The low-molecular-weight phosphotyrosine protein phosphatase, when overexpressed, reduces the mitogenic response to macrophage colony-stimulating factor and tyrosine phosphorylation of its receptor.

The interference of low-molecular-weight phosphotyrosine protein phosphatase with the macrophage response to macrophage colony-stimulating factor was investigated. This paper shows that this phosphatase, already known to be involved in platelet-derived growth factor receptor signaling, is physiologically expressed in murine macrophages and dephosphorylates in vitro macrophage colony-stimulating factor receptor molecules immunoprecipitated from macrophage colony-stimulating factor-stimulated macrophages. We obtained the first demonstration that a phosphotyrosine-specific protein phosphatase dephosphorylates the macrophage colony-stimulating factor receptor in vivo and reduces the mitogenic response to macrophage colony-stimulating factor. The data indicate that low-molecular-weight phosphotyrosine protein phosphatase is a negative regulator of macrophage colony-stimulating factor receptor signaling.

3T3 Cells↗
PubMed1998

Different in vitro and in vivo activity of low Mr phosphotyrosine protein phosphatase on epidermal growth factor receptor.

Low Mr phosphotyrosine protein phosphatase is a cytosolic enzyme which dephosphorylates platelet-derived growth factor and insulin receptor in vivo, thus reducing cellular mitogenic response to such growth factors. Following cell stimulation with platelet-derived growth factor the phosphatase undergoes a redistribution from the citosol to the Triton X-100-insoluble fraction where its activity upon the growth factor receptor is intense. Previous research uncovered evidence that low Mr phosphotyrosine protein phosphatase dephosphorylates the epidermal growth factor receptor in vitro. Here we demonstrate that in vivo the enzyme is not active on the phosphorylated epidermal growth factor receptor and it does not influence the mitogenic response of cells. Since the enzyme distribution is not affected by epidermal growth factor stimulation, involvement of a recruitment mechanism in the definition of low Mr phosphotyrosine protein phosphatase substrate specificity is hypothesized.

3T3 Cells↗
PubMed1998

Low molecular weight phosphotyrosine protein phosphatase translocation during cell stimulation with platelet-derived growth factor.

Low Mr phosphotyrosine protein phosphatase (PTP) is a cytosolic enzyme whose activity upon platelet-derived growth factor (PDGF) and insulin receptors has been demonstrated in vivo. In our study we demonstrate that this enzyme, both naturally expressed and overexpressed in NIH/3T3 fibroblasts, translocates from the cytosol to the Triton X-100 insoluble fraction following stimulation with PDGF. It emerges that the phosphorylation of a defined population of PDGF receptors, which is localized in this fraction and seems to be endowed with peculiar features and functions, is particularly affected by low Mr PTP overexpression.

3T3 Cells↗
PubMed1998

Gamma knife radiosurgery for large volume brain tumors: an analysis of acute and chronic toxicity.

Gamma Knife radiosurgery is often used to treat intracranial tumors <4 cm (approximately 13.5 cm3) in mean diameter. Larger lesions are rarely treated because of the expectation that increasing target volume will increase toxicity. We retrospectively analyzed 35 patients with primary or metastatic brain tumors of more than 13.5 cm3 treated with the Gamma Knife. Only 3 (8.5%) patients developed acute clinical toxicity. Nine (25%) patients developed post-Gamma Knife radionecrosis based on imaging studies, with only 3 of these patients (9% of the study population) having clinical progression of symptoms. Necrosis was not found to be related to prescribed dose, treatment volume or number of treated isocenters. We found no undue toxicity from the treatment of large brain tumors with the Gamma Knife.

Acute Disease↗
PubMed1997

Down-regulation of the nm23.h1 gene inhibits cell proliferation.

nm23 gene expression is strictly related to the state of cell growth. The level of its expression parallels the fraction of thymidine-incorporating cells (S-phase cells) in neoplastic mammary tissues and in the synchronously cycling fraction of MCF 1OA cells. nm23.h1 reaches a peak of expression in the S-phase, and is present at very low level during the GO/G1 phase. Two strategies are used to demonstrate the direct involvement of the nm23.h1 gene in the process of cell proliferation. The first consists of transient inhibition of nm23.h1 expression by using anti-sense oligonucleotide treatment; weak inhibitory effect on cell proliferation is observed. The second strategy involves the stable inhibition of nm23.h1 expression by transfection of MCF1OA cells with a plasmid vector expressing the human nm23.h1 anti-sense mRNA. The anti-sense-transfected cells show consistently slower proliferative activity than the control.

Breast↗
PubMed1997

Evidence for glutathione involvement in platelet-derived growth-factor-mediated signal transduction.

Recent studies show that glutathione, while being involved in the well-known physiological processes of amino acid transport and detoxification, can also play a part in cell proliferation events. Cell treatment with l-buthionine sulphoximine, which causes glutathione depletion, is accompanied by a decrease in cell proliferation. At present no precise relationship between this thiol and any critical intermediate of the mitogenic cascade has been proved. In this study, conducted on NIH/3T3 murine fibroblasts, we demonstrate a strict correlation between glutathione levels and platelet-derived growth-factor-receptor activation in response to stimulation and cell proliferation. The receptor autophosphorylation is severely impaired at low glutathione cellular levels. The interaction of glutathione with this growth-factor receptor in vivo, while being rather specific, is complex and may involve both cytosolic and extracellular receptor domains.

3T3 Cells↗
PubMed1997

NM23 gene expression in human breast carcinomas: loss of correlation with cell proliferation in the advanced phase of tumor progression.

NM23 is a protein associated with tumor progression, expressed in all tissues and in human tumors. Reduced expression of NM23.H1 is related to high incidence of lymph node and distant metastasis or to poor prognosis of the patient in several human malignant tumors. In this study we analyze NM23 expression in non-neoplastic mammary tissues surrounding the tumoral lesions, in human mammary carcinomas and in lymph node metastasis. Our analysis shows that NM23.H1 expression is lower in the mammary cells surrounding the tumor than in the tumor itself. In the primary tumors we observed a negative trend between degree of local invasion and level of NM23.H1 expression. A further decrease of NM23.H1 was detected in the invasive tumors that metastasized to axillary lymph nodes and in the metastasis. NM23.H2 was always more highly expressed than NM23.H1, and reduced expression of NM23.H1 but not NM23.H2 was concordant with the presence of lymph node metastasis or local invasiveness of the primary tumor. A positive correlation between NM23.H1 mRNA content and cell growth rate of breast tumor cells has been confirmed. However, this trend was not maintained in cancer cells from tumors that metastasized to axillary lymph nodes and in metastatic cells; in these 2 situations the NM23.H1 mRNA content varied without any relationship to the proliferative rate of the cells. In addition, in comparison with the initial tumor, the metastatic cell population showed a strong decrease of NM23.H1 expression and increased proliferative activity.

Biomarkers, Tumor↗
PubMed1997

Alteration of free calcium levels and acylphosphatase muscular isoenzyme in cultured dystrophic skin fibroblasts.

Levels of free intracellular calcium have been measured on two cell lines of cultured human fibroblasts carrying the genetic lesions occurring in Duchenne and Becker dystrophies. Both cell lines elicited a markedly higher content of the cation (98 nM and 57 nM, respectively) than control fibroblasts (35 nM). Differences toward controls were statistically significant (p < 0.01). Dystrophic fibroblasts were also found to possess a significantly reduced amount by about 50% of muscular acylphosphatase isoenzyme as compared to normal cells. As acylphosphatase was demonstrated to be involved in the regulation of Ca2+-ATPase activity from different sources, a hypothesis was formulated that could explain the disruption of calcium homeostasis as an effect of the altered acylphosphatase activity.

Acid Anhydride Hydrolases↗
PubMed1997

Neglect as a deficit determined by an imbalance between multiple spatial representations.

A previous study on neglect suggested that at least two hand parameters are crucial in producing an amelioration of neglect: the hand (left or right) and the spatial position of the hand (left or right). The improvement observed in perceiving left targets when the left hand acts in the left space can be due either to proprioceptive or to visual cuing. The stimulated left hand located in the left space may act as a powerful visual cue for the enhancement of the left visuo-spatial representation, in the same way as any other visual stimulus presented in the periphery of the visual field. Alternatively, it may be that the perceived hand location (due to the activation of the proprioceptive system) acts as an attentional field able to enhance the representation of the left space. In order to disentangle these two hypotheses, in the present study a naming task was executed by a group of neglect patients and by a control group. The subjects had to name all the objects depicted on a sheet of paper which were reflected on a mirror that inverted right and left space. While doing the naming performance, the subjects passively moved either the right or the left hand, in the left or right space. Stimuli and hand were reflected in the mirror that inverted right and left space and direct view of the stimuli and of the stimulated hand was prevented by a board. The results show that patients were more accurate at naming stimuli reflected in the left side of the mirror when the left hand was located and moved on the left side. In this condition, however, the left hand was seen in the right side of the mirror. It is therefore clear that the better performance was not due to visuo-spatial cuing but to a proprioceptive cuing effect. The results are discussed in terms of the relevance of personal and peripersonal spatial activation in the modulation of extrapersonal visual neglect. The coactivation of different spatial representations seems to be very influential on stimulus coding, thus confirming that spatial awareness is strictly related to the joint activity of multiple brain maps.

Aged↗
PubMed1996

Seventeen copies of the human 37 kDa laminin receptor precursor/p40 ribosome-associated protein gene are processed pseudogenes arisen from retropositional events.

A cDNA coding for a 37 kDa polypeptide has been identified in several species as both the potential precursor of the 67 kDa laminin receptor (37LRP) and a putative ribosome-associated protein (p40). Interestingly, increased expression of this polypeptide (37LRP/p40) is consistently observed in invasive and metastatic cancer cells and is associated with poor prognosis. Southern-blot analysis of human genomic DNA predicted multiple copies of the 37LRP/p40 gene. In this study, we report that the number of copies of this sequence in the human genome is 26 +/- 2. We have sequenced and analyzed 19 genomic clones corresponding to the 37LRP/p40 gene and found that they were all processed pseudogenes. They all lack intronic sequences and show multiple genetic alterations leading in some cases to the appearance of stop codons. Moreover, they all bear characteristic features of retroposons as the presence of a poly(A)-tail at their 3' end and short direct repeated flanking DNA sequences. None of the pseudogenes analyzed present cis-elements in their 5' flanking region such as TATA or GC boxes. Our date reveal that over 50% of the 37LRP/p40 gene copies are pseudogenes most probably generated by retropositional events. The finding of multiple pseudogenes for the 37LRP/p40 suggests that the accumulation of several copies of this gene might have given a survival advantage to the cell in the course of evolution.

Base Sequence↗
PubMed1996

pp60v-src phosphorylates and activates low molecular weight phosphotyrosine-protein phosphatase.

Low M(r) phosphotyrosine-protein phosphatase belongs to the non-receptor cytosolic phosphotyrosine-protein phosphatase subfamily. It has been demonstrated that this enzyme dephosphorylates receptor tyrosine kinases, namely the epidermal growth factor receptor in vitro and the platelet-derived growth factor receptor in vivo. Low M(r) phosphotyrosine-protein phosphatase is constitutively tyrosine-phosphorylated in NIH/3T3 cells transformed by pp60v-src. The same tyrosine kinase, previously immunoprecipitated, phosphorylates this enzyme in vitro as well. Phosphorylation is enhanced using phosphatase inhibitors and phenylarsine oxide-inactivated phosphatase, consistently with the existence of an auto-dephosphorylation process. Intermolecular dephosphorylation is demonstrated adding the active enzyme in a solution containing the inactivated and previously phosphorylated one. This tyrosine phosphorylation correlates with an increase in catalytic activity. Our results provide evidence of a physiological mechanism of low M(r) phosphotyrosine-protein phosphatase activity regulation.

3T3 Cells↗
PubMed1996

Anosognosia for hemiplegia, neglect dyslexia, and drawing neglect: clinical findings and theoretical considerations.

In this paper different models of anosognosia are confronted and data concerning denial behaviors are presented that were collected on a selected population of right brain-damaged patients affected by motor and neglect disorders. Anosognosia for motor impairment and anosognosia for cognitive impairments were found to be dissociated, as well as anosognosia for the upper and lower limb motor impairments. These findings are then discussed in an attempt to choose the more suitable theoretical framework for interpreting the various disorders related to denial of illness.

Aged↗
PubMed1995

Differential modulation of expression of the two acylphosphatase isoenzymes by thyroid hormone.

The modulation of expression of the skeletal muscle and erythrocyte acylphosphatase isoenzymes by thyroid hormone has been investigated. Our results indicate a differential regulation of the two enzymic isoforms by tri-iodothyronine (T3) in K562 cells in culture: an increase in the specific mRNA during T3-stimulation is shown only for the skeletal muscle isoenzyme. A fast and transient T3 induction of the accumulation of the specific mRNA can be observed, reaching a maximum 8 h after hormone treatment and then rapidly decreasing almost to the steady-state level after 24 h. A nuclear run-on assay was performed to explore the mechanisms of this regulation. These studies indicate that T3 induction of skeletal muscle acylphosphatase mRNA is due, at least in part, to a fast and transient increase in the rate of gene transcription, within 4 h after hormone administration. A very rapid decrease is then observed within a further 2 h. T3-dependent accumulation of the mRNA for the skeletal muscle acylphosphatase requires ongoing protein synthesis, as confirmed by inhibition with cycloheximide or puromycin. These findings indicate that the transcriptional regulation of the gene may be indirect.

Acid Anhydride Hydrolases↗
PubMed1995

PDGF receptor as a specific in vivo target for low M(r) phosphotyrosine protein phosphatase.

Low M(r) phosphotyrosine protein phosphatase (LMW-PTP) is a 18 kDa cytosolic enzyme widely distributed in eukaryotic cells. LMW-PTP catalyses the hydrolysis of phosphotyrosine residues and overexpression of the enzyme in normal and transformed cells inhibits cell proliferation. Site directed mutagenesis, together with crystallographic studies, have contributed to clarify the catalytic mechanism, which involves the active site signature sequence C12XXXXXR18, a main feature of all PTPase family members. In order to identify the LMW-PTP substrate/s we have expressed in NIH-3T3 cells a catalytically inert Cys12 to Ser phosphatase mutant which has preserved its capacity for substrate binding. Overexpression of the mutant phosphatase leads to enhanced cell proliferation and serum induced mitogenesis, indicating that the mutation results in the production of a dominant negative protein. Analysis of mutant LMW-PTP expressing cells has enabled us to demonstrate an association between LMW-PTP and platelet derived growth factor receptor that appears to be highly specific. Our data suggest a catalytic action of LMW-PTP on the phosphorylated platelet derived growth factor receptor.

3T3 Cells↗