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Biomedical subjects

F Conti

Publications and source records attributed to F Conti.

At least 37 records · Page 2Linked to original sources
PubMed1990

Pursuing the structure and function of voltage-gated channels.

A cyclical process of experimentation and theoretical analysis is being used to develop increasingly precise models of the structure and functional mechanisms of membrane proteins. Nucleic acid sequences have been determined for several voltage-gated sodium, calcium and potassium channels from invertebrates and vertebrates and from nerve and muscle tissues. Some of these sequences have been altered using site-directed mutagenesis. Properties of channels expressed after injection of normal and altered mRNA into Xenopus oocytes have been analysed by a variety of patch-clamp techniques. Preliminary structural models based on the first sequence information on sodium channels need to be modified to account for a large amount of new data. Here, Robert Guy and Franco Conti present their current view of the activation mechanism and ion selectivity of the voltage-gated channels.

Amino Acid Sequence↗
PubMed1990

Calcitonin gene-related peptide-positive neurons and fibers in the cat dorsal column nuclei.

An antiserum raised against the C-terminal region of rat alpha-calcitonin gene-related peptide has been used to investigate the morphology and topographical distribution of neurons and terminals containing calcitonin gene-related peptide in the cat dorsal column nuclear complex. Calcitonin gene-related peptide-positive fibers and axon terminals were denser in the cuneate nucleus than in the other dorsal column nuclei subdivisions and were observed throughout all rostrocaudal levels. They were densest in the dorsal and ventrolateral portions of the middle cuneate. Immunoreactive neurons were observed only in animals pre-treated with colchicine. In these cases, some calcitonin gene-related peptide-positive neurons were present in the cuneate and in the external cuneate. In double-labeling experiments, visualization of calcitonin gene-related peptide immunoreactivity in dorsal root ganglia neurons was combined with the retrograde transport of colloidal gold-labeled wheat germ agglutinin conjugated to inactive horseradish peroxidase injected in the cuneate nucleus. These experiments show that calcitonin gene-related peptide-positive fibers in the cuneate nucleus originate mostly from C3-C6 medium sized dorsal root ganglia neurons but also from some small and large neurons. These results suggest that calcitonin gene-related peptide-positive fibers may convey sensory information from a wide range of peripheral receptors.

Animals↗
PubMed1990

Substance P-containing projections in the dorsal columns of rats and cats.

Light and electron microscopic immunocytochemical methods were used to study the distribution and the morphology of substance P-positive fibers and axon terminals in the dorsal column nuclei of rats and cats, and to determine whether they are part of an ascending input to these nuclei. In rats, substance P-positive fibers and axon terminals are present throughout the rostrocaudal extent of the dorsal column nuclei. In cats, immunostained fibers and terminals are mostly confined to the ventral region of the caudal and middle portions of these nuclei but they are more homogeneously distributed at rostral levels. In both species, substance P-positive neurons are not present in the same nuclear complex. At the electron microscope level, substance P-positive terminals are small- to medium-sized and dome-shaped; they form asymmetric contacts on dendrites and contain many round, agranular vesicles and sparse dense core vesicles. In double-labeling experiments, visualization of substance P-immunoreactivity in the dorsal root ganglia and dorsal horn of the spinal cord was combined with the retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase or of colloidal gold-labeled wheat germ agglutinin conjugated to enzymatically inactive horseradish peroxidase. These experiments show that substance P-positive axon terminals may originate from both small dorsal root ganglion neurons and from spinodorsal column nuclei neurons in lamina IV. Although quantitative evaluation of the contribution of these two pathways to the substance P innervation of the dorsal column nuclei has not been performed and other sources cannot be discarded on the basis of the present evidence, it is proposed that non-primary afferents to the dorsal column nuclei account for most of the substance P-positive fibers and terminals in the dorsal column nuclei. The experiments support previous findings suggesting that nociceptive input may access the dorsal column nuclei and that this may be mediated, though to a very limited extent, directly by way of small dorsal root ganglion neurons.

Animals↗
PubMed1990

Abscisic acid-induced microheterogeneity in phospholipid vesicles. A fluorescence study.

Changes in the thermal behavior of DMPC (dimyristoyl-L-phosphatidylcholine) and an equimolar mixture of DMPC and DMPE (dimyristoyl-L-phosphatidylethanolamine) induced by the plant hormone abscisic acid (ABA) have been investigated using fluorescent probes. The fluorescence decay of the hydrophobic probe 1,6-diphenyl-1,3,5-hexatriene (DPH) in these vesicles has been measured using frequency-domain fluorometry, and has been analyzed using both models of discrete exponential components and continuous lifetime distributions. In the DMPC vesicles, using the distributional approach, higher center and width values were observed in the presence of abscisic acid (ABA), indicating a decrease in the dielectric constant of the lipid phase that we attribute to a decrease in the water concentration within the bilayer. Moreover, the presence of ABA in the liposomes increased the phospholipid phase transition temperature. The addition of ABA to the DMPC/DMPE mixture strongly increased the microheterogeneity of the system as reported by the FWHM (full-width at half-maximum) of the distributional approach.

Abscisic Acid↗
PubMed1990

[Carcinogenic perianal fistula].

The paper reports a case of anal fistula which led to the formation of a muco-secreting adenocarcinoma. The case is described in the context of other published case reports.

Adenocarcinoma, Mucinous↗
PubMed1990

31P nuclear magnetic resonance spectroscopy study on kidney preservation. Effect of verapamil.

31P NMR spectroscopy has been used to evaluate the usefulness of verapamil, a calcium channel blocker, in preventing ischemic renal damage. Phosphorylated metabolites have been investigated before, during and after 48 hrs of hypothermic storage. The rapidity in adenosine triphosphate resynthesis and the phosphomonoesters and phosphodiesters levels after reperfusion at the end of the storage period (48 hrs), were significantly higher in verapamil-treated kidneys. Phosphomonoesters to inorganic phosphate ratio, during the storage period, is even higher. These findings suggest that verapamil may protect against ischemic renal damage and so it can be useful for renal preservation. Furthermore, it has been shown that 31P NMR spectroscopy puts into evidence the biochemical recovery and allows the assessment of the viability of organs.

Animals↗
PubMed1989

Glutamate-positive neurons and axon terminals in cat sensory cortex: a correlative light and electron microscopic study.

Immunocytochemical methods were used to perform a correlative light and electron microscopic study of neurons and axon terminals immunoreactive to the antiglutamate (Glu) serum of Hepler et al. ('88) in the visual and somatic sensory areas of cats. At the light microscopic level, numerous Glu-positive neurons were found in all layers except layer I of both cortical areas. On the basis of the dendritic staining of Glu-positive cells, two major morphological categories were found: pyramidal cells, which were the most frequent type of immunostained neuron, and multipolar neurons, which were more numerous in layer IV of area 17 than in any other layer. A large number of Glu-positive neurons, however, did not display dendritic labelling and were considered unidentified neurons. Counts of labelled neurons were performed in the striate cortex; approximately 40% were Glu-positive. Numerous lightly stained punctate structures were observed in all cortical layers: the majority of these Glu-positive puncta were in the neuropil. After resectioning the plastic sections for electron microscopy it was observed that: 1) the majority of neurons unidentifiable at light microscopic level were indeed pyramidal neurons except in layer IV of area 17, where many stained cells were probably spiny stellate neurons. Some Glu-positive neurons, however, exhibited clear ultrastructural features of nonspiny nonpyramidal cells; 2) all synaptic contacts made by Glu-positive axon terminals were of the asymmetric type, but not all asymmetric synaptic contacts were labelled. The vast majority of postsynaptic targets of Glu-positive axons were unlabelled dendritic spines and shafts. The present results provide further evidence that Glu (or a closely related compound) is probably the neurotransmitter of numerous excitatory neurons in the neocortex.

Animals↗
PubMed1989

Structural parts involved in activation and inactivation of the sodium channel.

Structure-function relationships of the sodium channel expressed in Xenopus oocytes have been investigated by the combined use of site-directed mutagenesis and patch-clamp recording. This study provides evidence that the positive charges in segment S4 are involved in the voltage-sensing mechanism for activation of the channel and that the region between repeats III and IV is important for its inactivation.

Action Potentials↗
PubMed1989

Quantal charge redistributions accompanying the structural transitions of sodium channels.

Asymmetric displacement currents, Ig, associated with the gating of nerve sodium channels have been recorded in cell-attached macropatches of Xenopus laevis oocytes injected with exogenous mRNA coding for rat-brain-II sodium channels. The Ig properties were found to be similar to those of gating currents previously observed in native nerve preparations. Ig fluctuations were measured in order to ascertain the discreteness of the conformational changes which precede the channel opening. The auto-correlation of the fluctuations is consistent with a shot-like character of the elementary Ig contributions. The variance of the fluctuations indicates that most of the gating-charge movement that accompanies the activation of a single sodium channel occurs in 2 to 3 brief packets, each carrying an equivalent of about 2.3 electron charges.

Animals↗
PubMed1989

Intracellular magnesium blocks sodium outward currents in a voltage- and dose-dependent manner.

Tail currents through Na+ channels have been measured in inside-out patches from Xenopus laevis oocytes injected with cDNA-derived mRNA coding for the rat brain type II Na+ channel. It is shown that intracellular Mg2+ blocks outward currents in a voltage- and dose-dependent manner with a half blocking concentration between 3 and 4 mM at 0 mV and a voltage dependence of e-fold per 49 mV.

Animals↗
PubMed1989

Kidney disease of diabetes mellitus: NIDDK initiatives for the comprehensive study of its natural history, pathogenesis, and prevention.

Kidney disease of diabetes mellitus (KDDM) is the most common single cause of end-stage renal disease in the United States and western Europe. Diabetic patients have increased morbidity and mortality and are more likely to develop renal failure than the general US population. In addition, the 5-year survival of patients with KDDM who are receiving dialytic therapy is less than one-half that of patients without diabetes mellitus. The National Institute of Diabetes and Digestive and Kidney Diseases, in collaboration with public, private, and academic groups, has developed an implementation plan to enhance understanding of the underlying mechanisms in KDDM and to develop strategies to prevent the onset and the progression of KDDM.

Clinical Trials as Topic↗
PubMed1989

Calcitonin gene-related peptide (CGRP)-positive neurons and fibers in the cat periaqueductal grey matter.

The morphology and topographical distribution of neurons and terminals containing calcitonin gene-related peptide (CGRP) immunoreactivity in the cat periaqueductal grey (PAG) were studied using a rabbit antiserum raised against the C-terminal region of rat alpha-CGRP. In normal cats, numerous fibers, but rarely immunoreactive neurons, were observed in the PAG. CGRP-containing fibers showed bouton-like swellings along their length and expanded in terminal clusters of boutons. In many cases, CGRP-positive fibers were also observed in close association with small blood vessels. Immunoreactive fibers were particularly numerous at caudal PAG levels, mostly in its ventrolateral portion. In colchicine-treated cats, the pattern of CGRP-containing fibers was basically unchanged, despite a reduction of both the number of fibers and the intensity of fiber staining; in addition, numerous CGRP-positive neurons were found, mostly in the ventrolateral portion of the caudal PAG. These neurons were fusiform, spheroidal, and triangular in shape. The selective distribution of CGRP-positive elements in the PAG suggests a functional specialization of these neurons in the activation of pain-modulating mechanisms.

Animals↗
PubMed1988

Immunocytochemical evidence for glutamatergic cortico-cortical connections in monkeys.

Retrograde transport of horseradish peroxidase and immunocytochemical visualization of glutamate (Glu) were combined to investigate the neurotransmitter used by cortico-cortical neurons in the first (SI) and second (SII) somatic sensory areas of macaque monkeys. The majority of association and callosal neurons in SI and SII were immunoreactive for an antiGlu serum: evidence was therefore obtained in support of a role for Glu, or a closely related compound, as the synaptic transmitter used by cortico-cortical fibers.

Animals↗
PubMed1988

Demonstration of glutamate-positive axon terminals forming asymmetric synapses in cat neocortex.

Electron microscopic examination of sections immunocytochemically processed with an anti-glutamate serum reveals that many asymmetric synapses in the cat neocortex contain elevated levels of immunodetectable glutamate. These labelled axon terminals are likely to use glutamate as neurotransmitter. Axon terminals forming symmetric contacts were never labelled. Since glutamate is known to exert potent excitatory effects on neocortical neurons, the present finding gives immunocytochemical evidence that asymmetric synapses are excitatory.

Animals↗
PubMed1988

Orientation of the tryptophans responsible for the photoinactivation of nerve sodium channels.

UV irradiation of squid giant axons at wavelengths of 280 or 290 nm produces nearly the same rate of irreversible decrease of sodium currents. The rate of photodeactivation is unaffected by extensive removal of axoplasm with pronase, and it is independent of temperature in the range 5 degrees to 20 degrees C. The photochemical effect appears to be all or nothing. It does not alter the time course and the voltage dependence for activation and inactivation of the residual currents. Similar deactivation rates were produced by irradiations of the same intensity, but linearly polarized either parallel or perpendicular to the axon. The efficiency of the deactivation process is close to that expected if it was caused by the photooxidation of a single tryptophan residue per sodium channel. Owing to the geometry of the preparation the lack of polarization asymmetry suggests that this residue assumes nearly random (or pseudo-random) orientation in the three-dimensional structure of the sodium channel corresponding to the closed state.

Animals↗
PubMed1988

Biological activity of chitosan: ultrastructural study.

Reparative processes are reconstructive phenomena in which cellular elements and extracellular matrix glycoproteins interact to build the injured tissue. Biomaterials can be used to improve or stimulate reconstruction. In the present experimental investigation, tissue repair induced by chitosan, an 86.8% deacetylated poly(GlcNAc), was monitored by morphological analysis. To evaluate its biological role, chitosan was positioned in contact with dura mater or was used as a dura mater substitute. This polysaccharide, having structural characteristics similar to glycosaminoglycans, seems to mimic their functional behaviour. The inductive and stimulatory activity of chitosan on connective tissue-rebuilding is clearly demonstrated, and it is suggested that chitosan could be considered a primer on which a normal tissue architecture is organized.

Animals↗