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M L Rossi

Publications and source records attributed to M L Rossi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Nicotinic EPSCs in intact rat ganglia feature depression except if evoked during intermittent postsynaptic depolarization.

The involvement of the postsynaptic membrane potential level in controlling synaptic strength at the ganglionic synapse was studied by recording nicotinic fast synaptic currents (EPSCs) from neurons in the intact, mature rat superior cervical ganglion, using the two-electrode voltage-clamp technique. EPSCs were evoked by 0.05-Hz supramaximal stimulation of the preganglionic sympathetic trunk over long periods; their peak amplitude (or synaptic charge transfer) over time appeared to depend on the potential level of the neuronal membrane where the nicotinic receptors are embedded. EPSC amplitude remained constant (n = 6) only if ACh was released within repeated depolarizing steps of the postganglionic neuron, which constantly varied between -50 and -20 mV in consecutive 10-mV steps, whereas it decreased progressively by 45% (n = 9) within 14 min when the sympathetic neuron was held at constant membrane potential. Synaptic channel activation, channel ionic permeation and depolarization of the membrane in which the nicotinic receptor is localized must occur simultaneously to maintain constant synaptic strength at the ganglionic synapse during low-rate stimulation (0.03-1 Hz). Different posttetanic (20 Hz for 10 s) behaviors were observed depending on the mode of previous stimulation. In the neuron maintained at constant holding potential during low-rate stimulation, the depressed EPSC showed posttetanic potentiation, recovering approximately 23% of the mean pretetanic values (n = 10). The maximum effect was immediate in 40% of the neurons tested and developed over a 3- to 6-min period in the others; thereafter potentiation vanished within 40 min of 0.05-Hz stimulation. In contrast, no statistically significant synaptic potentiation was observed when EPSC amplitudes were kept constant by repeated -50/-20-mV command cycles (n = 12). It is suggested that, under these conditions, posttetanic potentiation could represent an attempt at recovering the synaptic strength lost during inappropriate functioning of the ganglionic synapse.

Acetylcholine↗
PubMed1999

Neutrophil infiltration into human gliomas.

Human gliomas were analysed for the infiltration of neutrophils using immunohistochemistry by staining sections for CD15-positive and myeloperoxidase-positive cells. Over 70% of all glioma samples analysed (n = 105) had significant neutrophil infiltration, but there was a marked and significant correlation between tumour grade and the extent of the neutrophil infiltration. In the low grade tumours only 40-50% had significant infiltration, while in glioblastoma multiforme over 85% of the samples analysed had significant infiltration. Numbers of neutrophils infiltrating glioblastoma multiforme tumours were also greater than in the other tumour groups. Circulating white blood cell counts were elevated above the normal range in all glioma patients, but this elevation was entirely due to increased numbers of circulating neutrophils. Again, the highest numbers of circulating neutrophils were seen in the glioblastoma multiforme patients. These experiments indicate that glioma-derived factors may directly or indirectly affect the number of circulating neutrophils and influence their infiltration into the tumours.

Bone Marrow↗
PubMed1999

Mutation in the PTEN/MMAC1 gene in archival low grade and high grade gliomas.

The PTEN gene, located on 10q23.3, has recently been described as a candidate tumour suppressor gene that may be important in the development of advanced cancers, including gliomas. We have investigated mutation in the PTEN gene by direct sequence analysis of PCR products amplified from samples microdissected from 19 low grade (WHO Grade I and II) and 27 high grade (WHO grade III and IV) archival, formalin-fixed, paraffin-embedded gliomas. Eleven genetic variants in ten tumours have been identified. Eight of these are DNA sequence changes that could affect the encoded protein and were present in 0/2 pilocytic astrocytomas, 0/2 oligoastrocytomas, 0/1 oligodendroglioma, 0/14 astrocytomas, 3/13 (23%) anaplastic astrocytomas and 5/14 (36%) glioblastomas. PTEN mutations were found exclusively in high grade gliomas; this finding was statistically significant. Only two of the PTEN genetic variants have been reported in other studies; two of the genetic changes are in codons in which mutations have not been found previously. The results of this study indicate that mutation in the PTEN gene is present only in histologically more aggressive gliomas, may be associated with the transition from low histological grade to anaplasia, but is absent from the majority of high grade gliomas.

Adolescent↗
PubMed1999

Neurohypophyseal pilocytic astrocytoma invading the skull base.

We describe the clinical presentation, neuroradiological and histological findings of an unusual case of pilocytic astrocytoma of the neurohypophysis, and discuss the related surgical and prognostic issues of this neoplasm which invaded the skull base and the sphenoid sinus. Only four histologically proven cases of such a tumour have been reported in the English literature, and the pathological features and behaviour of this neoplasm still await definition.

Aged↗
PubMed1999

Participation of a chloride conductance in the subthreshold behavior of the rat sympathetic neuron.

The presence of a novel voltage-dependent chloride current, active in the subthreshold range of membrane potential, was detected in the mature and intact rat sympathetic neuron in vitro by using the two-microelectrode voltage-clamp technique. Hyperpolarizing voltage steps applied to a neuron held at -40/-50 mV elicited inward currents, whose initial magnitude displayed a linear instantaneous current-voltage (I-V) relationship; afterward, the currents decayed exponentially with a single voltage-dependent time constant (63.5 s at -40 mV; 10.8 s at -130 mV). The cell input conductance decreased during the command step with the same time course as the current. On returning to the holding potential, the ensuing outward currents were accompanied by a slow increase in input conductance toward the initial values; the inward charge movement during the transient ON response (a mean of 76 nC in 8 neurons stepped from -50 to -90 mV) was completely balanced by outward charge displacement during the OFF response. The chloride movements accompanying voltage modifications were studied by estimating the chloride equilibrium potential (E(Cl)) at different holding potentials from the reversal of GABA evoked currents. [Cl(-)](i) was strongly affected by membrane potential, and at steady state it was systematically higher than expected from passive ion distribution. The transient current was blocked by substitution of isethionate for chloride and by Cl(-) channel blockers (9AC and DIDS). It proved insensitive to K(+) channel blockers, external Cd(2+), intracellular Ca(2+) chelators [bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA)] and reduction of [Na(+)](e). It is concluded that membrane potential shifts elicit a chloride current that reflects readjustment of [Cl(-)](i). The cell input conductance was measured over the -40/-120-mV voltage range, in control medium, and under conditions in which either the chloride or the potassium current was blocked. A mix of chloride, potassium, and leakage conductances was detected at all potentials. The leakage component was voltage independent and constant at approximately 14 nS. Conversely, gCl decreased with hyperpolarization (80 nS at -40 mV, undetectable below -110 mV), whereas gK displayed a maximum at -80 mV (55.3 nS). Thus the ratio gCl/gK continuously varied with membrane polarization (2.72 at -50 mV; 0.33 at -110 mV). These data were forced in a model of the three current components here described, which accurately simulates the behavior observed in the "resting" neuron during membrane migrations in the subthreshold potential range, thereby confirming that active K and Cl conductances contribute to the genesis of membrane potential and possibly to the control of neuronal excitability.

Animals↗
PubMed1998

Evaluation of neuronal loss, astrocytosis and abnormalities of cytoskeletal components of large motor neurons in the human anterior horn in aging.

In order to identify possible morphological changes which occur in the anterior horn of normal individuals during aging, 40 controls with no neurological disease were studied. Brain and spinal cord tissue was processed according to a brain banking protocol. Controls were grouped according to age in 10 year intervals. Serial sections (20 microm) of formalin fixed, paraffin-embedded tissue were obtained, from each cervical, thoracic and lumbar spinal cord segment. Every 5th section (until 2 mm) was stained with haematoxylin and eosin and the numbers of motor neurons in the anterior horn counted at x400 magnification. Descriptive statistical analysis was performed using the SPSS program. Parallel sections (5 microm) of the same spinal segments were immunostained with a panel of antibodies including glial fibrillary acidic protein (GFAP), tau, ubiquitin and two phosphorylated neurofilaments subunits. Significant neuronal loss with aging was found by regression line analysis where three equations were used to calculate the number of motor neurons by age in each spinal segment. In 24/40 cases spheroids were observed and they were more numerous in the lumbar segment. GFAP staining revealed a distinctive cellular pattern in the anterior horn of oldest cases. Large and intensely stained astrocytes were seen in the anterior horn of cases aged over 75 years. The number of astrocytes increased progressively with age up to 70 years. Some of the changes observed in the present study may be the result of a selective vulnerability of large motor neurons to aging which could play an important role in the progression of MND. Most of these changes may also have similar pathophysiological mechanisms.

Adult↗
PubMed1998

Monoclonal antibodies against vascular endothelial antigens expressed in normal human brain.

A panel of monoclonal antibodies reactive with human-brain vessels was raised by immunizing BALB/c mice with homogenate of whole human brain, obtained from temporal lobectomies. Hybridoma supernates were screened by immunohistochemical methods on frozen sections of human brain, liver and spleen and 16 clones were isolated. The pattern of immunoreactivity varied with respect to the type of brain blood vessels predominantly labelled and to tissue specificity. Some antibodies cross-reacted with cow or squirrel monkey forebrain microvessels with an intensity equal to that shown by human brain. The immunoreactivity patterns reflected antigenic heterogeneity among different subsets of vascular endothelial cells in human brain.

Animals↗
PubMed1998

Pathology of choroid plexus papillomas: a review.

Choroid plexus papillomas (CPPs) are rare, usually slow growing neoplasms. Their biological behaviour cannot be predicted in an individual case. Furthermore, the neuropathological diagnosis of these neoplasms is occasionally difficult because light and electron microscopical and immunohistochemical features may overlap with those of other neoplasms localising in the choroid plexus. The aim of this paper is to review the pathological literature (light and electron microscopy (EM) and immunocytochemistry), to provide guidance on current diagnostic tools and criteria and address the identification of 'atypical' CPPs, e.g. those CPPs with histological features indicative of aggressive behaviour, in an attempt to help bridge the diagnostic gap between benign CPPs on the one hand and choroid plexus carcinomas (CPCs) on the other.

Adenocarcinoma↗
PubMed1998

The effects of perilymphatic tonicity on endolymph composition and synaptic activity at the frog semicircular canal.

The effects of changes in perilymphatic tonicity on the semicircular canal were investigated by combining the measurements of transepithelial potential and endolymphatic ionic composition in the isolated frog posterior canal with the electrophysiological assessment of synaptic activity and sensory spike firing at the posterior canal in the isolated intact labyrinth. In the isolated posterior canal, the endolymph was replaced by an endolymph-like solution of known composition, in the presence of basolateral perilymph-like solutions of normal (230 mosmol/kg), reduced (105 mosmol/kg, low NaCl) or increased osmolality (550 mosmol/kg, Na-Gluconate added). Altered perilymphatic tonicity did not produce significant changes in endolymphatic ionic concentrations during up to 5 min. In the presence of hypotonic perilymph, decreased osmolality, K and Cl concentrations were observed at 10 min. In the presence of hypertonic perilymph, the endolymphatic osmolality began to increase at 5 min and by 10 min Na concentration had also significantly increased. On decreasing the tonicity of the external solution an immediate decline was observed in transepithelial potential, whereas hypertonicity produced the opposite effect. In the intact frog labyrinth, mEPSPs and spike potentials were recorded from single fibers of the posterior nerve in normal Ringer's (240 mosmol/kg) as well as in solutions with modified tonicity. Hypotonic solutions consistently decreased and hypertonic solutions consistently increased mEPSP and spike frequencies, independent of the species whose concentration was altered. These effects ensued within 1-2 min after the start of perfusion with the test solutions. In particular, when the tonicity was changed by varying Na concentration the mean mEPSP rate was directly related to osmolality. Size histograms of synaptic potentials were well described by single log-normal distribution functions under all experimental conditions. Hypotonic solutions (105 mosmol/kg) markedly shifted the histograms to the left. Hypertonic solutions (380-550 mosmol/kg, NaCl or Na-Gluconate added) shifted the histograms to the right. Hypertonic solutions obtained by adding sucrose to normal Ringer's solution (final osmolality 550 mosmol/kg) increased mEPSP and spike rates, but did not display appreciable effects on mEPSP size. All effects on spike discharge and on mEPSP rate and size were rapidly reversible. In Ca-free, 10 mM EGTA, Ringer's solution, the sensory discharge was completely abolished and did not recover on making the solution hypertonic. These results indicate that perilymphatic solutions with altered tonicity produce small and slowly ensuing changes in the transepithelial parameters which may indirectly affect the sensory discharge rate, whereas relevant, early and reversible effects occur at the cytoneural junction. In particular, the modulation of mEPSP amplitude appears to be postsynaptic; the presynaptic effect on mEPSP rate of occurrence is presumably linked to local calcium levels, in agreement with previous results indicating that calcium inflow is required to sustain basal transmitter release in this preparation.

Action Potentials↗
PubMed1998

Impact of clinical pathways for total hip replacement: a community-based analysis.

The implementation of clinical pathways for total hip replacement was carried out by five hospitals in the metropolitan area of Syracuse, New York. This process occurred under the leadership of clinical nurse specialists and nurse managers. It was supported by preadmission patient education programs and active physician involvement. The participating hospitals shared utilization quality assurance data and benchmarked with respect to the experience of Sacramento, California, and each others' progress. The effort produced substantial reductions in hospital stays without adverse impacts on quality of care.

Arthroplasty, Replacement, Hip↗
PubMed1998

Synaptic current at the rat ganglionic synapse and its interactions with the neuronal voltage-dependent currents.

The membrane current activated by fast nicotinic excitation of intact and mature rat sympathetic neurons was studied at 37 degrees C, by using the two-microelectrode voltage-clamp technique. The excitatory postsynaptic current (EPSC) was modeled as the difference between two exponentials. A fast time constant (tau2; mean value 0.57 ms), which proves to be virtually voltage-independent, governs the current rise phase and a longer time constant (tau1; range 5.2-6.8 ms in 2 mM Ca2+) describes the current decay and shows a small negative voltage dependence. A mean peak synaptic conductance of 0.58 muS per neuron is measured after activation of the whole presynaptic input in 5 mM Ca2+ external solution (0.40 muS in 2 mM Ca2+). The miniature EPSCs also rise and decay with exponential time constants very similar to those of the compound EPSC recorded at the same voltage. A mean peak conductance of 4.04 nS is estimated for the unitary event. Deconvolution procedures were employed to decompose evoked macrocurrents. It is shown that under appropriate conditions the duration of the driving function describing quantal secretion can be reduced to <1 ms. The shape of the EPSC is accurately mimicked by a complete mathematical model of the sympathetic neuron incorporating the kinetic properties of five different voltage-dependent current types, which were characterized in a previous work. We show that IA channels are opened by depolarizing voltage steps or by synaptic potentials in the subthreshold voltage range, provided that the starting holding voltage is sufficiently negative to remove IA steady-state inactivation (less than -50 mV) and the voltage trajectories are sufficiently large to enter the IA activation range (greater than -65 mV). Under current-clamp conditions, this gives rise to an additional fast component in the early phase of membrane repolarization-in response to voltage pulses-and to a consistent distortion of the excitatory postsynaptic potential (EPSP) time course around its peak-in response to the synaptic signal. When the stimulation initiates an action potential, IA is shown to significantly increase the synaptic threshold conductance (up to a factor of 2 when IA is fully deinactivated), compared with that required when IA is omitted. The voltage dependence of this effect is consistent with the IA steady-state inactivation curve. It is concluded that IA, in addition to speeding up the spike repolarization process, also shunts the excitatory drive and delays or prevents the firing of the neuron action potential.

Action Potentials↗
PubMed1998

In vitro effects of GM-CSF on mature peripheral blood neutrophils.

GM-CSF can play a crucial role in regulating the neutrophil-mediated inflammatory response. This growth factor is a proliferative stimulus for bone marrow neutrophil stem cell precursors and has at least 3 important roles in regulating neutrophil-mediated immunity: a) a direct effect on the proliferation and development of neutrophil progenitors; b) synergistic activity with other haemopoietic growth factors; c) stimulation of the functional activity of mature neutrophils. The production of GM-CSF may be triggered directly by exogenous factors such as antigens and endotoxins, or indirectly through the release of cytokines by a variety of cells including lymphocytes, activated macrophages and endothelial cells exposed to products of mononuclear phagocytes. Such production of GM-CSF may serve to quickly release mature neutrophils from the bone marrow in response to infections. Moreover, enhancement of the function of mature neutrophils may also augment their ability to migrate to infective sites and then phagocytose and kill pathogens. Increased expression of CD11b/CD18 may play a fundamental part in this mechanism because this receptor is essential for the adhesion of neutrophils to the endothelium. Both phagocytosis and oxidative burst activity increase as a result of the action of GM-CSF and the increased expression of complement- and Fc-receptors can augment opsono-phagocytosis. A further level of neutrophil up-regulation occurs by increasing the functional life span of neutrophils by GM-CSF. Thus, by delaying neutrophil apoptosis, GM-CSF greatly extends the time over which neutrophils may function at inflammatory sites. GM-CSF can thus exert a variety of important regulatory controls of neutrophil function during bacterial infections. Both the number and the functional status of neutrophils is highly regulated by GM-CSF. It is also possible that GM-CSF produced within localised sites of acute inflammation or infection may attract, trap and then activate neutrophils within this site.

Annexin A5↗
PubMed1997

Aging and the nigro-striatal pathway.

Aging is associated with a progressive impairment in motor function. This feature, together with the decline in mental function, could be considered as an aging syndrome which may finally compromise the ability of the elderly to maintain an active, independent life-style. In the present paper a wide variety of morphological aspects, which have been classically related to brain aging and others such as cytoskeletal changes, the role of growth factors and molecular changes, will be reviewed focusing on aging of the nigrostriatal pathway. In addition to sharing features of aging common to other structures, it is likely that the nigrostriatal pathway has specific characteristics derived from its particular molecular characteristics and/or from a selective vulnerability to aging. To gain further insight into the aging syndrome, the acquisition of rigorous criteria for selecting control cases is paramount. The improvement of methods for the preservation of human tissue is also crucial.

Aged↗
PubMed1997

Molecular aspects of neuro-oncology.

Detailed understanding of molecular events responsible for brain tumor growth is a prerequisite for the development of effective therapeutic modalities leading to improved prognosis and cure. Advances in molecular biology in the past decades have revolutionized our understanding of cancer, including brain tumors. We have learned that abnormal proliferation, inability of the cells to die and their potential to modify their tissue environment result from accumulation of genetic aberrations. This article reviews genetic mechanisms implicated in the pathogenesis of nervous system tumors, such as unactivation of tumor suppressor and replication error genes, generation of abnormal growth factor loops, alterations of apoptotic pathways and angiogenesis.

Apoptosis↗
PubMed1997

Cerebellar cortex delayed maturation in sudden infant death syndrome.

The cerebellum shows afferent and efferent connections with intrinsic bulbar nuclei and plays an important role in respiration and cardiovascular control. Pathological and neurochemical abnormalities of bulbar nuclei including the arcuate nucleus have been postulated in sudden infant death syndrome (SIDS). Most of these abnormalities have been related to impairment in brain development. The cerebellar cortex has a well-documented evolution from fetal life until infancy; thus, it may be a very good model to assess brain maturation in SIDS. The present study was conducted to investigate changes in the cerebellar cortex in 19 SIDS cases compared with 12 age-related controls using morphological, quantitative, and statistical approaches. Five-microns paraffin sections from the midsagittal cerebellar vermis were stained with hematoxylin and eosin (H&E). Immunohistochemical staining was carried out using a polyclonal antiserum to glial fibrillary acidic protein (GFAP). Each case consisted of a 25-microns parallel paraffin section stained with H&E, where the cerebellar external granular layer (EGL) cell density was obtained in one field magnification (x1,000) using an optical dissector procedure on the basis of a stereological method. A statistically significant high EGL cell density, mostly related to the presence of immature bipolar, elongated neuronal cells of the premigratory zone with hyperchromatic, oval or poor differentiated nuclei, was observed in SIDS. In these cases, EGL expressed immunoreactivity for GFAP mainly in the subpial and the postmitotic zone. These findings demonstrate a delayed or slower decline in the number of EGL neurons in SIDS, suggesting either a prolongation of the growth phase related to postnatal cerebellar foliation or a delay in inward migration. These results suggest that in SIDS there is delayed maturation of the cerebellar cortex/EGL, which may support the hypothesized cardiopulmonary control dysfunction, leading to death in a vulnerable period of postnatal development.

Adult↗
PubMed1997

Prognostic analysis of astrocytic gliomas correlating histological parameters with the proliferating cell nuclear antigen labelling index (PCNA-LI).

Eighty out of 250 cases of astrocytic glioma collected from a practice served by a single clinical team over a 15-year period were studied using a full complement of clinical, follow up, histopathological analysis and proliferating cell nuclear antigen (PCNA) immunostaining for the obtention of the PCNA-labelling index (LI). A statistical evaluation and discriminant analysis were carried out with the aim of clarifying the importance of various parameters as predictors of tumor behaviour. Data are correlated with survival (with a 10-year follow up). A significant correlation with survival was found when histological grouping and the PCNA-LI were studied with the Cox test. Most significant features were histological as detected using classical techniques including histological grading. The utilization of objective values (mitosis, cellular density and necrosis) appears to be useful in grading astrocytic tumors. Our results emphasize the importance of cytological, histological and PCNA-LI parameters as predictors of tumor behaviour.

Adolescent↗
PubMed1996

The effect of clofilium, a K-channel blocker, on the electrogenic K secretion and the sensory discharge at the frog semicircular canal.

Potassium transport by dark cells produces marked K-concentration differences between endo- and perilymphatic fluids in labyrinthine organs and generates the transepithelial potential. The ensuing electrochemical potential for K sustains the transduction current which regulates activity at the cytoneural junction. Clofilium, a compound which is known to block cardiac K channels and to decrease the endocochlear potential, was applied to the endolymphatic side of the isolated frog semicircular canal. The drug abolished the transepithelial potential and increased K outflux from the lumen to the dark cells (or the basolateral perilymph) with no apparent interference with active K secretion. When applied to the perilymphatic side in the intact labyrinth, clofilium reduced the rate of occurrence of miniature excitatory postsynaptic potentials (mEPSPs), both at rest and in response to mechanical stimulation (sinusoidal rotation at 0.1 Hz, 12.5 deg/s2 peak acceleration). This effect may be related to a reduced K-electrochemical unbalance and a decreased transduction current. The drug consistently reduced mEPSP size, although amplitude distributions remained log-normal and time intervals between successive mEPSPs remained exponentially distributed; this suggests a direct effect of clofilium on the postsynaptic membrane, in addition to any possible presynaptic effects. Spike discharge by the afferent fibre was almost completely abolished at rest and responses to mechanical stimulation were reduced by 85-90%. These effects cannot be accounted for by the mild reduction of mEPSP rates and confirm a direct action of clofilium on the afferent postsynaptic terminal.

Animals↗