The PU.1 transcription factor induces cyclin D2 expression in U937 cells.
Explore the source record for details and available documents.
Cyclin D2↗
Biomedical subjects
M Gulisano
Publications and source records attributed to M Gulisano.
Vitamin D receptor gene polymorphism is not associated with psoriasis in the Italian Caucasian population.
Explore the source record for details and available documents.
Gene Frequency↗
Modification of plasma glycosaminoglycans in long distance runners.
BACKGROUND: It is well documented that exercise reduces the risk of thromboembolic disease, possibly by increasing the plasma concentration of anticoagulant-antithrombotic compounds. OBJECTIVES: As plasma glycosaminoglycans (GAGs) play a role in the anticoagulant-antithrombotic potential of plasma, to examine the concentration and profile of these compounds in well trained, long distance runners and sedentary subjects. METHODS: Plasma GAGs were measured in 10 male, long distance runners and 10 sedentary counterparts before and after ergometric tests. GAGs were extracted, purified, and identified by electrophoretic and enzymatic methods, and measured as hexosamine. RESULTS: Plasma GAGs found in sedentary subjects were slow migrating heparan sulphates I and II, keratan sulphate I, and chondroitin 4-6-sulphate. Those found in trained athletes were slow migrating heparan sulphate I, chondroitin 4-6-sulphate (or keratan sulphate I), and fast migrating heparan sulphate. Total plasma concentrations of GAGs were higher in athletes than in sedentary subjects at rest. In sedentary subjects, plasma GAGs did not change after cycle ergometric exercise at 80% of their anaerobic threshold. However, the appearance of a novel band of heparan sulphate migrating faster than fast migrating heparan sulphate was observed in athletes after exercise. CONCLUSIONS: Exercise changes the amount and profile of plasma GAGs; these changes may play a role in protecting subjects who practise aerobic sports against developing cardiovascular disease.
Adult↗
Bio-Alcamid, a novel prosthetic polymer, does not interfere with morphological and functional characteristics of human skin fibroblasts.
Explore the source record for details and available documents.
Acrylic Resins↗
Tangential migration of cells from the basal to the dorsal telencephalic regions in the chick.
The evolutionary relationship between telencephalic regions of the avian and mammalian brains has been a long-standing issue in comparative neuroanatomy. Based on various criteria, a number of homologous regions have been proposed. Recent studies in mammals have shown that basal regions of the telencephalon give rise to neurons that migrate dorsally and populate the cerebral cortex. In the present study we demonstrate that, similar to mammals, neurons from a ventricular region of the palaeo-striatal complex - the dorsal subpallial sulcus - of the chick telencephalon migrate dorsally to populate the developing pallium. Further characterization of these cells revealed that they express the neurotransmitter gamma-aminobutyric acid, but not the calcium-binding protein calbindin. These findings provide evidence that the mouse and chick basal regions are not only homologous in terms of gene expression patterns and connectivity, but they both also contribute inhibitory interneurons to dorsal regions of the developing telencephalon.
Animals↗
Relationship between the calibre of carotid arteries and the configuration of the circle of Willis in healthy older persons.
AIM: Recent papers have pointed out that the severity of brain damage that follows carotid occlusion is largely influenced by the state of integrity and functionality of the circle of Willis. In spite of this, duplex scanning investigation of carotid arteries has traditionally been focused on the assessment of the degree of the stenosis, while other features, such as the calibre of carotid arteries and their possible asymmetry, have often been neglected. The aim of the present paper was to verify, in a cohort of older persons, whether, based on the calibre of internal carotid arteries and their possible asymmetry, abnormalities of the circle of Willis can be predicted. Such information could be used to identify high risk patients in whom the status of the circle of Willis should be investigated by MR angiography. METHODS: We studied 118 healthy older persons with both duplex scanning investigation of carotid arteries and MR angiography of the circle of Willis. RESULTS: We found that the finding of abnormal internal carotid artery calibres was always associated with abnormalities of the precommunicating segments either of the anterior or of the posterior cerebral arteries. Abnormalities of communicating arteries did not affect the calibre of internal carotid arteries, but abnormalities of anterior communicating arteries could always be detected by contralateral common carotid artery compression manoeuvres. CONCLUSION: In conclusion our findings show that, in healthy older persons, duplex scanning investigation of carotid arteries may provide useful information about the integrity and functionality of the circle of Willis. Future studies should confirm our findings in patients with atherosclerotic lesions of internal carotid arteries.
Aged↗
Is the percentage of stenosis of the internal carotid artery a reliable measure of the risk of ischemic stroke? A morphometric study by duplex ultrasound of aortic arch branches in 500 normal adults.
BACKGROUND: The percentage of stenosis has been considered for the last 20 years, and still continues to be, the main criterion of choice between a surgical and a medical treatment of the atherosclerotic lesions of the aortic arch branches, particularly as regards the internal carotid artery. On the other side, it has been demonstrated that the risk of adverse acute cerebrovascular events, besides being related to the characteristics of the plaque, such as softness, subintimal haemorrhage or surface ulcer, is strictly related to the actual residual lumen of the internal carotid artery. The pre-eminent role of the percentage of stenosis in the choice of the treatment, hence, presumes a narrow range of variation of the original calibre of the vessel, yet to be proven. METHODS: Five-hundred normal adults underwent the measurement of the internal calibre of the aortic arch branches by duplex ultrasound in order to find out their actual range of variation. RESULTS: The range of variation of the internal calibre of the aortic arch branches, expressed as the ratio between the maximum and the minimum value found for each vessel, was very wide in all cases (from 180% for the right common carotid artery to 340% for the right vertebral artery). With reference to the internal carotid arteries, the range of variation was 219% for the right internal carotid artery and 241% for the left internal carotid arteries. CONCLUSIONS: Due to the wide range of variation of the original calibre of the aortic arch branches, the percentage of stenosis alone cannot be considered an accurate measure of the severity of the stenosis, and hence a reliable criterion of choice of the treatment.
Adult↗
Collateral circulation in internal carotid artery occlusion. A study by duplex scan and magnetic resonance angiography.
BACKGROUND: Clinical effects of internal carotid artery (ICA) occlusion may range from the absolute absence of symptoms to lethal hemispheric stroke. In this paper symptoms of patients with ICA occlusion have been related to the development of collateral circulation, different types of developed collateral circulation have been assessed, and the degree of sensitivity and specificity of duplex scan has been appraised. METHODS: Forty-eight patients with ICA occlusion or subocclusion, 24 males and 24 females, aged between 50 and 83 years (67.7+/-7.15), underwent duplex scan and magnetic resonance (MR) angiography. Nineteen patients were completely asymptomatic, 20 patients showed permanent neurological symptoms and 9 patients had shown transient symptoms. RESULTS: Twelve patients (25%) did not show any collateral circulation, 29 patients (60%) showed collateral circulation through homolateral external carotid artery branches and 7 patients (15%) showed collateral circulation through other circuits. Of the 20 patients with permanent symptoms only 8 showed collateral circulation. On the contrary, all the 19 asymptomatic patients and the 9 patients with transient symptoms showed collateral circulation. Eventually, duplex scan showed 78% sensitivity, 100%, specificity and 83% diagnostic accuracy. CONCLUSIONS: Our data show: 1) a clear-cut prevalence of collateral circulation through homolateral external carotid artery branches with respect to other possible collateral circulation; 2) an inverse relationship between the development of collateral circulation and the appearance of permanent symptoms; 3) a good diagnostic accuracy of duplex scan in revealing collateral circulation in the case of ICA occlusion.
Aged↗
The circle of Willis in healthy older persons.
BACKGROUND: The current indication for carotid surgery is based upon the percentage of stenosis of the internal carotid artery. This approach shows many limitations, one of which is to presume the anatomical completeness of the circle of Willis in all patients who are evaluated. On the contrary, there is increasing evidence of a great natural variability in the configuration of the circle of Willis. METHODS: The aim of the present paper was to investigate, by magnetic resonance angiography, the variability of the circle of Willis in a cohort of 118 healthy older persons. RESULTS: The circle of Willis showed an entirely complete configuration in 47% of the subjects, a complete configuration of its anterior part in 90% of the subjects, and a complete configuration of its posterior part in 48.5% of the subjects. CONCLUSIONS: These findings confirm the great variability of the circle of Willis even in healthy older persons and suggest that, in indicating carotid surgery, the configuration of the circle of Willis should also be taken into account.
Age Factors↗
Dynamic domains of gene expression in the early avian forebrain.
The expression domains of genes implicated in forebrain patterning often share borders at specific anteroposterior positions. This observation lies at the heart of the prosomeric model, which proposes that such shared borders coincide with proposed compartment boundaries and that specific combinations of genes expressed within each compartment are responsible for its patterning. Thus, genes such as Emx1, Emx2, Pax6, and qin (Bf1) are seen as being responsible for specifying different regions in the forebrain (diencephalon and telencephalon). However, the early expression of these genes, before the appearance of putative compartment boundaries, has not been characterized. In order to determine whether they have stable expression domains before this stage, we have compared mRNA expression of each of the above genes, relative both to one another and to morphological landmarks, in closely staged chick embryos. We find that, between HH stage 8 and HH stage 13, each of the genes has a dynamic spatial and temporal expression pattern. To test for autonomy of gene expression in the prosencephalon, we grafted tissue from this region to more caudal positions in the neural tube and analyzed for expression of Emx1, Emx2, qin, or Pax6. We find that gene expression is autonomous in prosencephalic tissue from as early as HH stage 8. In the case of Emx1, our data suggest that, from as early stage 8, presumptive telencephalic tissue also is committed to express this gene. We propose that early patterning along the anteroposterior axis of the presumptive telencephalon occurs across a field that is subdivided by different combinations of genes, with some overlapping areas, but without either sharp boundaries or stable interfaces between expression domains.
Amino Acid Sequence↗
Otx genes in brain morphogenesis.
Most of the gene candidates for the control of developmental programmes that underlie brain morphogenesis in vertebrates are the homologues of Drosophila genes coding for signalling molecules or transcription factors. Among these, the orthodenticle group includes the Drosophila orthodenticle (otd) and the vertebrate Otx1 and Otx2 genes, which are mostly involved in fundamental processes of anterior neural patterning. These genes encode transcription factors that recognise specific target sequences through the DNA binding properties of the homeodomain. In Drosophila, mutations of otd cause the loss of the anteriormost head neuromere where the gene is transcribed, suggesting that it may act as a segmentation "gap" gene. In mouse embryos, the expression patterns of Otx1 and Otx2 have shown a remarkable similarity with the Drosophila counterpart. This suggested that they could be part of a conserved control system operating in the brain and different from that coded by the HOX complexes controlling the hindbrain and spinal cord. To verify this hypothesis a series of mouse models have been generated in which the functions of the murine genes were: (i) fully inactivated, (ii) replaced with each others, (iii) replaced with the Drosophila otd gene. Otx1-/- mutants suffer from epilepsy and are affected by neurological, hormonal, and sense organ defects. Otx2-/- mice are embryonically lethal, they show gastrulation impairments and fail in specifying anterior neural plate. Analysis of the Otx1-/-; Otx2+/- double mutants has shown that a minimal threshold level of the proteins they encode is required for the correct positioning of the midbrain-hindbrain boundary (MHB). In vivo otd/Otx reciprocal gene replacement experiments have provided evidence of a general functional equivalence among otd, Otx1 and Otx2 in fly and mouse. Altogether these data highlight a crucial role for the Otx genes in specification, regionalization and terminal differentiation of rostral central nervous system (CNS) and lead to hypothesize that modification of their regulatory control may have influenced morphogenesis and evolution of the brain.
Animals↗
Emx1 is a marker for pyramidal neurons of the cerebral cortex.
The homeobox-containing gene, Emx1, a mouse homologue of Drosophila empty spiracles, is specifically expressed in the developing telencephalic cortex. It has been reported that Emx1 transcripts and the protein product are localized in most cells of the cerebral cortex during the process of proliferation, migration, differentiation and maturation. We provide evidence here, based on a multitude of experimental approaches in developing rats, in support of the hypothesis that the expression of this gene is restricted to pyramidal neurons. Specifically, we found that, similar to pyramidal neurons, cells expressing Emx1 are distributed in all cortical layers, except layer I. Using in situ hybridization and immunocytochemistry at the light and electron microscope levels, we have shown that the density, distribution, soma shape and ultrastructural features of these cells were identical to those of pyramidal neurons. Double-labelling experiments confirmed that the vast majority of Emx1-expressing cells also contained glutamate, a marker of pyramidal neurons. We also found that this gene is expressed by most glutamate-containing neurons in dissociated cortical cell cultures and the vast majority of cells in radially arranged clones of pyramidal cells in the cortices of chimeric mice. Thus, the homeobox gene Emx1 can be reliably used as a marker of the pyramidal cell lineage.
Age Factors↗
Cx36 is dynamically expressed during early development of mouse brain and nervous system.
Connexins are structural proteins that are part of the gap junctional channels which couple cells in different tissues. Connexin36 (Cx36) is a new member of the connexin gene family, found to be expressed essentially if not exclusively in neuronal cells in adult CNS of mouse, rat and man. Here we have studied Cx36 expression during murine embryonic development. Cx36 shows a highly dynamic pattern of expression. It is first (E9.5) evident in the forebrain and later its expression expand caudally in the midbrain. At E12.5 its expression correlates with major morphogenetic boundaries in the developing mouse brain, specifically with the dorsoventral telencephalic boundary and the Zona Limitans Intrathalamica. Starting at midgestation (E12.5), it is also expressed in both sympathetic and spinal ganglia, and in two longitudinal stripes along the spinal cord.
Animals↗
Genomic organization and chromosomal localization of the mouse Connexin36 (mCx36) gene.
Connexin36 (Cx36) is a new connexin that was recently cloned in mouse, rat and human. It is highly expressed in neurons of the CNS. To gain insight into the transcriptional regulation of this gene, we have cloned the genomic region containing the entire mCx36 gene and sequenced about 7.6kb around the coding region. The computer analysis of this sequence was helpful in defining putative regulative sequences. Using both 5'-RACE and RNAse protection assay, we have mapped the transcription starting site commonly used in both adult olfactory bulb and brain, in position -479 from the ATG. By 3'-RACE, we defined the polyadenylation site used that is located 1436nt downstream the stop codon. The expected transcript is 2875nt long and is consistent with the 2.9kb transcript found in the same tissues by Northern blot. Finally, we have mapped mCx36 on chromosome 2 in the position F3 in a region that is synthenic to human chromosome 15q14, where the human Cx36 gene has been recently mapped.
Animals↗
Expression of connexin36 mRNA in adult rodent brain.
A new member of the connexin gene family, named Connexin36 (Cx36) has, recently, been identified in rodents and shown to be preferentially, if not exclusively, expressed in neurones of the adult CNS. In this study we present a detailed in situ hybridization analysis of the expression pattern of mouse Connexin 36 (mCx36) mRNA in the adult mouse brain, with particular regards to the correlation of mCx36 expression to specific neuronal cell classes and systems. We found that mCx36 was strongly and widely expressed in the brain, including areas where the presence of gap junctions was never detected before. Quantitative analysis of the hybridization signal indicated varying levels of expression in different areas. In particular mCx36 was highly expressed in the neurones at different levels of the motor pathway, the olfactory pathway, the hippocampus, and areas related to the generation of respiratory rhythm. On the contrary, mCx36 was more heterogeneously expressed in nuclei of the sensory pathways. These findings show that mCx36 is the first connexin specifically expressed in neuronal cells in the adult rodent brain. The profiles of expression clearly indicate that mCx36 might play specific roles within different neuronal systems.
Age Factors↗
Genetic and molecular roles of Otx homeodomain proteins in head development.
Insights into the molecular mechanisms underlying neural development in vertebrates come from the cloning and the functional analysis of genes which are involved in the molecular pathways leading to neural induction, tissue specification and regionalization of the brain. Among them, transcription factors belonging to the orthodenticle family (Otx1, Otx2) play an important role during early and later events required for proper brain development. To better understand their functions, several mouse mutants have been generated by homologous recombination. Their analysis clearly indicates that Otx1 is involved in corticogenesis, sense organ development and pituitary functions, while Otx2 is necessary earlier in development, for the correct anterior neural plate specification and organisation of the primitive streak. A molecular mechanism depending on a precise threshold of OTX proteins is necessary for the correct positioning of the isthmic region and for anterior brain patterning. Finally, vertebrate Otx genes share functional equivalence with the Drosophila homologue otd, indicating that the genetic mechanisms underlying pattern formation in insect and mammalian brain development are evolutionarily conserved.
Animals↗
Signalling from tyrosine kinases in the developing neurons and glia of the mammalian brain.
Explore the source record for details and available documents.
Animals↗
Gemcitabine plus vinorelbine in advanced non-small cell lung cancer: a phase II study of three different doses. Gem Vin Investigators.
Our aim was to study the activity and toxicity of the gemcitabine plus vinorelbine (Gem Vin) combination and to identify the optimal dose. Previously untreated patients aged < 70 years, with stage IV or IIIb (not candidates for radiotherapy) non-small cell lung cancer were eligible. Studied dose-levels of Gem Vin, administered on days 1 and 8 every 3 weeks, were (mg m(-2)): level I = 1000/25; level II = 1200/25; level III = 1000/30; level IV = 1200/30. A feasibility study was performed at each dose-level, followed by a single-stage phase II study. Dose-level IV was unfeasible because of grade 4 neutropenia. Overall, out of 126 patients enrolled in phase II studies, there were one complete and 32 partial responses (response rate 26%: 95% CI 18-34%). Response rates were 27.9%, 21.4% and 29.3% at levels I, II and III, respectively. The treatment was well tolerated. Toxicity was less frequent and severe at level I. Overall median survival was 33 weeks (95% CI 28-40). Descriptive quality of life analysis showed that patients with a worse baseline global health status score tended to drop out of the study earlier than those with a better score. Gem Vin is feasible at different doses. It is sufficiently active and well tolerated. A phase III study to compare the effect on quality of life of Gem Vin (level I) vs cisplatin-based chemotherapy is ongoing.
Adult↗