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Biomedical subjects

F Conti

Publications and source records attributed to F Conti.

At least 19 recordsLinked to original sources
PubMed1992

Numerous SP-positive pyramidal neurons in cat neocortex are glutamate-positive.

An immunocytochemical technique that allows visualization of two antigens in the same neuron was used to verify the possibility that some neocortical pyramidal neurons contain both glutamate (Glu) and substance P (SP) immunoreactivity. The results show that a large fraction of SP-positive pyramidal neurons are also Glu-positive, and indicate that in a small population of cortical neurons a fast excitatory synaptic transmitter and a slow peptidic modulator coexist.

Animals↗
PubMed1992

Substance P-containing pyramidal neurons in the cat somatic sensory cortex.

Light and electron microscopic immunocytochemical methods were used to verify the possibility that neocortical pyramidal neurons in the first somatic sensory cortex of cats contain substance P. At the light microscopic level, substance P-positive neurons accounted for about 3% of all cortical neurons, and the vast majority were nonpyramidal cells. However, 10% of substance P-positive neurons had a large conical cell body, a prominent apical dendrite directed toward the pia, and basal dendrites, thus suggesting they are pyramidal neurons. These neurons were in layers III and V. At the electron microscopic level, the majority of immunoreactive axon terminals formed symmetric synapses, but some substance P-positive axon terminals made asymmetric synapses. Labelled dendritic spines were also present. Combined retrograde transport-immunocytochemical experiments were also carried out to study whether substance P-positive neurons are projection neurons. Colloidal gold-labelled wheat germ agglutinin conjugated to enzymatically inactive horseradish peroxidase was injected either in the first somatic sensory cortex or in the dorsal column nuclei. In the somatic sensory cortex contralateral to the injection sites, a few substance P-positive neurons in layers III and V also contained black granules, indicative of retrograde transport. This indicates that some substance P-positive neurons project to cortical and subcortical targets. We have therefore identified a subpopulation of substance P-positive neurons that have most of the features of pyramidal neurons, are the probable source of immunoreactive axon terminals forming asymmetric synapses on dendritic spines, and project to the contralateral somatic sensory cortex and dorsal column nuclei. These characteristics fulfill the criteria required for classifying a cortical neuron as pyramidal.

Amino Acid Sequence↗
PubMed1992

Treatment of bone metastases with dichloromethylene bisphosphonate.

PURPOSE: The study was undertaken to evaluate the effects of dichloromethylene bisphosphonate (Cl2MDP) on osteolytic and osteoblastic bone lesions from a variety of tumoral primary sites and to investigate the in vivo mechanism underlying the action of this drug. PATIENTS AND METHODS: Seventy-six patients participated in the current study: 59 had predominantly osteolytic lesions and 17 osteoblastic metastases. Sixteen patients had hypercalcemia. All of the patients received 300 mg of Cl2MDP intravenously (IV) for 7 days and then 200 mg of Cl2MDP intramuscularly (IM) for 14 days. Biochemical parameters were measured in the patients before the start of treatment and 3, 7, 14, and 21 days after beginning treatment. After the withdrawal of parenteral Cl2MDP, 59 patients with predominantly osteolytic lesions were then randomized to receive chemotherapy alone (group A, 29 cases) or chemotherapy plus Cl2MDP given at an oral dose of 1,200 mg/d (group B, 30 cases). RESULTS: Serum calcium (Ca), urinary calcium (UCa) phosphate (UPO4), and hydroxyproline (HOP) excretion levels significantly decreased in all patients, whereas no significant changes occurred in serum alkaline phosphatase (AlkPh) and bone Gla-protein (BGP) levels. In 56 patients with painful bone lesions, a progressive analgesic effect was observed mainly between day 7 and day 14. In patients with predominantly osteoblastic metastases, the Cl2MDP treatment led to a more evident hypocalcemia and an increase in both AlkPh and BGP. However, in the majority of these patients the hypocalcemia was corrected by the concurrent use of effective cytotoxic treatments capable of reducing osteoblast stimulation. During 6 months of follow-up, two pathologic fractures occurred in patients of group A, and none occurred in patients of group B. CONCLUSIONS: We conclude that Cl2MDP was effective in patients presenting bone metastases with and without hypercalcemia. Care should be taken particularly in those patients with mixed metastases when the sclerotic component is predominant, as the drug may enhance the possibility of hypocalcemia, which is generally corrected by effective cytotoxic drugs. Therefore, Cl2MDP can be considered a valuable support in the treatment of bone metastases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Use of ultrasonography in morphofunctional evaluation of orthotopic neo-bladder].

Seventeen patients submitted to radical cystectomy and orthotopic bladder replacement according to Reddy's technique were studied at the 1, 3, 6 and 12-month, then annually follow-up by physical examination, intravenous pyelogram, cystourethrography, suprapubic and transrectal ultrasonography and complete urodynamics. Sixteen patients (94%) reported day-time urinary continence and twelve patients (70%) day-time and nocturnal continence. Cysto-manometry showed a mean bladder capacity of 450 cc with a maximal endocavitary pressure of 40 cm. H2O and satisfactory peak flow rate. Vesico-ureteral reflux was never detected at roentgenography. Ultrasonography may be useful in the study of a possible reflux or stenosis of the neovesico-ureteral junction by detecting renal scars or dilatation of the renal cavities. Sovrapubic ultrasonography can quantify the capacity of the neo-bladder (300-600 cc), study its shape, walls and contractions that do not cause the involuntary opening of the neo-bladder neck. Transrectal ultrasonography studies the bladder neck shape and its dynamic function. Residual urine volume never exceeded 50 cc. Ultrasonography demonstrated its effectiveness and reliability and limited the application of more invasive roentgenographic procedures.

Cystectomy↗
PubMed1991

Mapping the site of block by tetrodotoxin and saxitoxin of sodium channel II.

The SS2 and adjacent regions of the 4 internal repeats of sodium channel II were subjected to single mutations involving, mainly, charged amino acid residues. These sodium channel mutants, expressed in Xenopus oocytes by microinjection of cDNA-derived mRNAs, were tested for sensitivity to tetrodotoxin and saxitoxin and for single-channel conductance. The results obtained show that mutations involving 2 clusters of predominantly negatively charged residues, located at equivalent positions in the SS2 segment of the 4 repeats, strongly reduce toxin sensitivity, whereas mutations of adjacent residues exert much smaller or no effects. This suggests that the 2 clusters of residues, probably forming ring structures, take part in the extracellular mouth and/or the pore wall of the sodium channel. This view is further supported by our finding that all mutations reducing net negative charge in these amino acid clusters cause a marked decrease in single-channel conductance.

Action Potentials↗
PubMed1991

Modulation of the free sphingosine levels in Epstein Barr virus transformed human B lymphocytes by phorbol dibutyrate.

The amounts of free sphingosine in Epstein Barr virus transformed B lymphocytes (EBV-B) treated with sphingosine and phorbol-12,13-dibutyrate (PD) has been quantified by high performance liquid chromatography (HPLC). PD treatment did not affect intracellular sphingosine level, while it seems to lessen the removal of this long chain base in sphingosine-treated EBV-B cells. The previous results relative to sphingosine-dependent changes in choline-metabolite levels have to be interpreted on the basis of these results.

B-Lymphocytes↗
PubMed1991

Modulation of human lymphoblastoid B cell line by phorbol ester and sphingosine. A 31P-NMR study.

Changes in phospholipid and energy metabolism in Epstein-Barr Virus transformed B lymphocytes (EBV-B), induced by phorbol 12,13-dibutyrate (PD) and sphingosine (an inhibitor of protein kinase C), have been evaluated by 31P-NMR spectroscopy. The effects of PD and sphingosine on [3H]thymidine incorporation have also been studied. An increase in phosphorylcholine (PCho) levels has been observed in sphingosine and sphingosine + PD treated cells after 30 min of incubation, whereas no change was observed in lymphocytes incubated with PD during the same period. Extracellular choline levels increased in sphingosine treated cells but decreased in PD treated cells. Hence, a sphingosine-dependent hydrolysis of choline-linked phospholipids is suggested. A time-dependent reduction of PCho observed after 120 min PD incubation is consistent with an increase of the synthesis of choline-linked phospholipids.

B-Lymphocytes↗
PubMed1991

Competitive blockage of the sodium channel by intracellular magnesium ions in central mammalian neurones.

The aim of this study was to determine from macroscopic current analysis how intracellular magnesium ions, Mgi2+, interfere with sodium channels of mammalian neurones. It is reported here that permeation across the sodium channel is voltage- and concentration-dependently reduced by Mgi2+. This results in a general reduction of sodium membrane conductance and an outward sodium peak current at large positive potentials. 30 mM Mgi2+ leads ot a negative shift of voltage dependence of sodium channel gating parameters, probably due to the surface potential change of the membrane. This shift alone is, however, insufficient to explain the reduction of outward sodium currents. The blockage by Mgi2+ is decreased upon increasing intracellular or extracellular Na+ concentration, which suggests that Mgi2+ interferes with sodium permeation by competitively occupying sodium channels. Using a kinetic model to describe the sodium permeation, the dissociation constant (at zero membrane potential) of Mgi2+ for the sodium channel has been calculated to be 8.65 +/- 1.51 mM, with its binding site located at 0.26 +/- 0.05 electrical distance from the inner membrane. This dissociation constant is smaller than that of Nai+, which is 83.76 +/- 7.60 mM with its binding site located at 0.75 +/- 0.23. The low dissociation constant of Mgi2+ reflects its high affinity for the sodium channel.

Animals↗
PubMed1991

Gating currents of inactivating and non-inactivating potassium channels expressed in Xenopus oocytes.

The Xenopus oocyte expression system in combination with patch-clamp techniques allows the measurement of ionic currents from a single class of genetically engineered ion channels. Ionic currents in the nanoampere range from oocytes injected with cRNA, corresponding to potassium channels, can be recorded in the inside-out patch configuration. These recordings have a high time resolution at low background noise. Substitution of impermeant ions for potassium and blocking of the channel conductance with tetraethylammonium allows the recording of potassium gating currents, Ig, which is hampered in natural excitable cells by the simultaneous presence of sodium channels and a variety of different potassium channels. The "on" transients, Ig(on), are fast and can have amplitudes of up to several tens of pA. Upon repolarization to -100 mV after small depolarizations, "off" gating currents, Ig(off)g, which reverse most of the "on" charge displacement, Q(on), within 1 ms, are readily observed. However, this fast recovery of the gating charge is drastically reduced upon increasing the amplitude of the depolarizing pulse. In contrast to sodium channels, this temporary charge immobilization is complete within a few milliseconds at positive membrane potentials. Furthermore, there seems to be no direct correlation between charge immobilization and inactivation because the same phenomenon occurs for channels that do not inactivate.

Animals↗
PubMed1991

Single point mutations of the sodium channel drastically reduce the pore permeability without preventing its gating.

1. Two mutants of the sodium channel II have been expressed in Xenopus oocytes and have been investigated using the patch-clamp technique. In mutant E387Q the glutamic acid at position 387 has been replaced by glutamine, and in mutant D384N the aspartic acid at position 384 has been replaced by asparagine. 2. Mutant E387Q, previously shown to be resistant to block by tetrodotoxin (Noda et al. 1989), has a single-channel conductance of 4 pS, that can be easily measured only using noise analysis. At variance with the wild-type, the open-channel current-voltage relationship of mutant E387Q is linear over a wide voltage range even under asymmetrical ionic conditions. 3. Mutant D384N has a very low permeability for any of the following ions: Cl-, Na+, K+, Li+, Rb+, Ca2+, Mg2+, NH+4, TMA+, TEA+. However, asymmetric charge movements similar to the gating currents of the Na(+)-selective wild-type are still observed. 4. These results suggest that residues E387 and D384 interact directly with the pathway of the ions permeating the open channel.

Animals↗
PubMed1991

Transient cerebral ischemia in the rat: a study by nuclear magnetic resonance spectroscopy.

The energy state and the levels of metabolites involved in the phospholipid turnover during and following a transient cerebral ischemia have been evaluated with the aids of 31P and 1H nuclear magnetic resonance spectroscopy. Ischemia was induced by electrocoagulation of vertebral arteries in combination with transient occlusion of both common carotid arteries. After 10-min ischemia, the brain energy charge and the levels of high-energy phosphates were reduced, whereas lactic acid levels had undergone an 8-fold increase. Sixty minutes after cerebral blood flow recovery, brain energy charge and levels of high-energy phosphates returned to basal values, whereas lactic acid levels remained persistingly elevated; an increase in phosphocreatine was also observed. At this same time, glycerolphosphorylcholine levels were found to be significantly reduced.

Animals↗
PubMed1991

31P and 1H NMR studies of ethanolamine-linked phosphoglycerides metabolism in human T lymphocytes.

Aqueous and organic extracts of peripheral human T lymphocytes and of T lymphoblastoid cell lines have been examinated by 31P and 1H NMR spectroscopy in order to study the metabolism of ethanolamine (Etn) linked phosphoglycerides. The results show that the Etn concentration in the culture medium determines the composition of Etn-containing metabolites and phospholipids. The effect of phorbol esters, stimulating the synthesis and the breakdown of choline-containing phospholipids has been also studied. A phorbol 12-myristate 13-acetate (PMA) dependent membrane phosphatidylethanolamine hydrolysis, presumably mediated by protein kinase C activity, has been demonstrated.

Cells, Cultured↗
PubMed1990

Aging brain: effect of acetyl-L-carnitine treatment on rat brain energy and phospholipid metabolism. A study by 31P and 1H NMR spectroscopy.

The effects of acetyl-L-carnitine (ALCAR) on metabolites involved in energy and phospholipid metabolism have been evaluated by mean of 31P and 1H NMR spectroscopy on adult (6 months) and old (24 months) rat brains. A significant increase of glycerophosphorylcholin (GroPCho) in aged rat brain has been observed as compared with adult rat brain. No variations in ATP, phosphocreatine (PCr), Cr, lactate, ADP and inorganic phosphate (Pi) levels have been found between aged and adult brains. Treatment with ALCAR caused a significant increase in PCr levels and a decrease in lactate and sugar phosphate in adult and aged rat brain. These results are suggestive of treatment with ALCAR being responsible for a reduction in brain glycolytic flow and for enhancing the utilization of alternative energy sources, such as lipid substrates or ketone bodies. Furthermore, the changes in GroPCho levels observed after treatment with ALCAR may be indicative of a modulating effect on the activity of the enzymes involved in the acylation-re-acylation process of membrane phospholipids.

Acetylcarnitine↗
PubMed1990

Sodium ionic and gating currents in mammalian cells.

Ionic and gating currents from voltage-gated sodium channels were recorded in mouse neuroblastoma cells using the path-clamp technique. Displacement currents were measured from whole-cell recordings. The gating charge displaced during step depolarizations increased with the applied membrane potential and reached saturating levels above 20 mV. Prolonged large depolarizations produced partial immobilization of the gating charge, and only about one third of the displaced charge was quickly reversed upon return to negative holding potentials. The activation and inactivation properties of macroscopic sodium currents were characterized by voltage-clamp analysis of large outside-out patches and the single-channel conductance was estimated from non-stationary noise analysis. The general properties of the sodium channels in mouse neuroblastoma cells are very similar to those previously reported for various preparations of invertebrate and vertebrate nerve cells.

Animals↗