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Biomedical subjects

I Ferrer

Publications and source records attributed to I Ferrer.

At least 253 records · Page 14Linked to original sources

Stereotaxic administration of 1-methyl-4-phenylpyridinium ion (MPP+) decreases striatal fructose 2,6-bisphosphate in rats.

The stereotaxic administration of 1-methyl-4-phenylpyridinium ion (MPP+) into the neostriatum of male rats caused a lesion that resulted in a large dose-dependent loss of striatal fructose 2,6-bisphosphate; initial values were restored 5 days after the treatment. This effect was not protected by systemic administration of MK-801 or by nitroarginine. The content of hexose 6-phosphates and ATP was also reduced by MPP+ treatment, whereas lactate was increased. Biochemical and histological results suggested that MPP+ caused a nonselective cell death, followed by a pronounced astroglial response, parallel to fructose 2,6-bisphosphate recovery. The stereotaxic administration of rotenone showed a different time effect on fructose 2,6-bisphosphate cerebral content, with a significantly faster recovery. These results indicate that cerebral fructose 2,6-bisphosphate may be a sensitive metabolite related to brain damage caused by potent neurotoxins such as MPP+. On the other hand, they show that MPP+ acts in the brain through a quick, strong cytotoxic mechanism, which probably involves mechanisms other than mitochondrial chain blockage.

1-Methyl-4-phenylpyridinium↗

Congenital muscular dystrophy with distinct CNS involvement.

The sixth child of non-consanguineous parents, who had suffered from severe arthrogryposis syndrome and microcephalia, died at the age of two days. Post-mortem study revealed unique morphological brain anomalies characterized by severe cerebral and cerebellar atrophy, focal cerebral mycrogiria and ectopic masses of immature cells in the periventricular region and cerebral white matter; pachygyria was absent. In addition, muscular examination was consistent with severe muscular dystrophy. These findings suggest that new forms of combined cerebral abnormalities and muscular dystrophy of congenital origin can be recognized in isolated cases.

Autopsy↗

Effects of X-irradiation on glial cells in the developing rat brain.

Sprague-Dawley rats were given a single dose of 2 Gy X-rays when 1 or 3 days of age. Dying cells in the germinal layer of the telencephalon reached peak values 6 h after irradiation; dead cells were cleared 48 h later. These effects were almost abolished with the injection of cycloheximide (1 microgram/g body weight) given at the time of irradiation. PCNA-immunoreactive cells (cells in late G1 and S phases of the cell cycle) and PCNA-negative cells were sensitive to X-rays. Long-term effects on glial cell populations in the subcortical white matter of the cingulum were examined in irradiated rats, killed at postnatal day 30 (P30), by means of glial fibrillary acidic protein, vimentin and S-100 immunohistochemistry, as well as with anti-TGF-alpha (transformerly growth factor) antibodies that are used as putative oligodendroglial cell markers in the white matter of rat. The subcortical white matter was reduced in irradiated animals, mainly in rat irradiated at P3, as revealed with myelin basic protein immunohistochemistry. Quantitative studies showed no significant differences in the number of glial cells in animals irradiated at P1 when compared with age-matched controls. However, reduced numbers of vimentin-, S-100-, and TGF-alpha-immunoreactive cells were found in animals irradiated at P3. These features indicate a limited capacity of surviving germinal cells, in animals irradiated at P3, to give rise to normal values of glial cells in the white matter in rat aged 30 days. This limitation mainly affects putative oligodendrocytes and glial cell precursors.

Animals↗

The Purkinje cell in olivopontocerebellar atrophy. A Golgi and immunocytochemical study.

Purkinje cells were examined in three familial cases of olivopontocerebellar atrophy (OPCA) by means of the Golgi method, and neurofilament and calcium-binding protein immunocytochemistry. Reduced dendritic arborizations, as seen with different techniques, early formation of axonal spheroids, and abnormal accumulation of phosphorylated neurofilament epitopes in dendrites, somata and axonal spheroids, together with limited formation of proximal spine-like protrusions were the main changes in Purkinje cells. These lesions are unlikely to be the consequence of anterograde degeneration secondary to olivary atrophy, as postulated by some investigators, but probably represent primary damage to Purkinje cells in patients with OPCA. Reduced dendritic arborizations result in a decrease of receptor sites for parallel fibres and deprive granule cells of their main targets. Abnormal accumulation of neurofilaments in somata, dendrites and axonal spheroids may contribute to an abnormal transport and may impair protein turnover in the distal regions of Purkinje cells.

Adult↗

Parvalbumin immunohistochemistry in denervated skeletal muscle.

Parvalbumin is a calcium-binding protein which, in muscle, is mainly found in type 2B fibres, whereas type 1 fibres lack parvalbumin immunoreactivity. Previous studies have shown that this pattern is highly dependent upon motor neuron innervation and is modified in denervated, cross-reinnervated or chronic low-frequency stimulated muscles. In the present study, we have examined the modifications of parvalbumin immunocytochemistry in the anterior tibialis muscle of the rat at different intervals following section of the sciatic nerve. During the first 2 weeks after denervation, no changes in parvalbumin immunoreactivity were seen, although a global reduction of fibre diameter was observed. Three weeks after denervation, small angulated, strongly parvalbumin-immunoreactive fibres appeared. From the second month onwards, the pattern of parvalbumin immunohistochemistry was characterized by areas composed of small, strongly immunoreactive fibres separated by less atrophic areas displaying a normal chequerboard distribution of parvalbumin immunoreactivity. The increase of parvalbumin-immunoreactivity in denervated and reinnervated muscle, as seen in our study, indicates that important changes in parvalbumin distribution occurs in muscle fibres after denervation. These changes are probably produced in an attempt to bind the free cytosolic calcium which accumulates in denervated fibres, and further reinforces the role of parvalbumin in calcium homeostasis during denervation and reinnervation.

Adenosine Triphosphatases↗

Evidence of nuclear DNA fragmentation following hypoxia-ischemia in the infant rat brain, and transient forebrain ischemia in the adult gerbil.

Wistar rats, eight days old, were subjected to permanent bilateral forebrain ischemia, followed by hypoxia for 15 minutes. A cerebral infarct, mainly involving the cerebral neocortex, hippocampus, amygdala, striatum and subcortical white matter was produced. Neurons and glia showing punctate chromatin condensation and karyorrhectic cells were observed 12 hours after hypoxia-ischemia. Their number increased during the first two days and recruitment of cells with degenerating nuclei occurred until day five. In situ labeling of nuclear DNA fragmentation stained many normal-appearing nuclei, as well as punctate chromatin condensations and nuclear fragments in karyorrhectic cells. Delayed neuronal death in the CA1 area of the hippocampus was observed after 20 minutes of transient forebrain ischemia in the adult gerbil. In situ labeling of nuclear DNA fragmentation demonstrated stained punctate chromatin condensation in a few degenerating cells at 48 hours post-ischemia. Substantial labeling of CA1 neurons occurred in the fourth day. Agarose gel electrophoresis of extracted brain DNA from ischemic infant rats and adult gerbils showed a ladder-type pattern which is typical of nuclear DNA fragmentation into oligonucleosomal fragments (internucleosomal cleavage). These findings suggest that endonuclease(s) activation may play a role in cell death induced by different forms of hypoxia-ischemia.

Animals↗

[Alien limb behavior associated with Alzheimer's disease].

A 48-year-old female developed apraxia, followed by aphasia and dementia. Clinical examination also showed an alien member sign, supranuclear gaze paresis, myoclonus and rigidity on the right arm. The examination of the frontal lobe biopsy showed typical lesions of Alzheimer's disease as the only neuropathological abnormality. The association of this clinical syndrome with Alzheimer's pathology is unusual.

Alzheimer Disease↗

[Dysphagia as the only manifestation of inclusion body myositis].

We report a 72-year-old woman with dysphagia as the only manifestation of inclusion body myositis (IBM). Although electrophysiological examination revealed subclinical abnormalities in limb muscles, dysphagia was the only symptom 4 years after the onset of the disease. Muscle biopsy showed rimmed vacuoles and cytoplasmic inclusions together with lymphocytic inflammation. IBM must be included in the differential diagnosis of isolated dysphagia.

Aged↗

Diarrhea associated with intestinal inflammation increases the potency of mu and delta opioids on the inhibition of gastrointestinal transit in mice.

The aim of the study was to determine the effects of intestinal inflammation induced by croton oil on the antitransit action of systemically administered receptor-specific opioids. Our hypothesis was that inflammation would "sensitize" opioid receptors in peripheral and/or central terminals of myenteric and submucous plexus neurons and enhance the effects of exogenously administered opioids. Diarrhea was induced by p.o. administration of croton oil and was demonstrated by weight loss and increased gastrointestinal transit. Histologically, an increased number of clear vesicles in the cytoplasm of jejunal epithelial cells and enlarged spaces filled with fine granular material in the extravascular compartment were observed. Subcutaneous morphine and fentanyl produced dose-related inhibitions of gastrointestinal transit in saline-treated controls with ED50 values of 1.24 +/- 0.06 and 0.036 +/- 0.010 mg/kg, respectively. In animals with diarrhea, dose-response curves were parallel and shifted to the left with a significant decrease in ED50 values of 2.95 times for morphine and 1.89 for fentanyl. The effects of the delta agonist Tyr-D-Pen-Gly-Phe-D-Pen, but those of U50,488H [trans-3,4-dichloro-N-methyl-N-(2-(1-pyrrolydynil)cyclohexyl) benzeneazetamine] also were increased significantly during diarrhea associated with inflammation. Naloxone (0.1 mg/kg), MR-2266 [(-)-a-5,9-diethyl-2'-hydroxy-2-(3-furylmethyl)-6,7-benzomorphan] (3 mg/kg) and naltrindole (1 mg/kg) antagonized the effects of the receptor-specific opioid agonists used in the study. Our results show that the potency of s.c. mu and delta opioids is increased during inflammation of the gut and that the effect is mediated by the same type of opioid receptors present in the noninflamed tissue. These results support the view that a sensitization of opioid receptors occurs during acute inflammation of the gut.

Amino Acid Sequence↗

[Analytic preoperative control and serum alaninaminotransferase (ALT) activity].

A standard model of analytical preoperative profile does not exist, so we decided to perform a wide profile. In this revision, we studied the utility of determining serum ALT activity in analytical preoperative controls, searching for the causes of its elevation in pediatric patients who would undergo minor surgery. Of the 3,750 patients analysed, 1.57% showed elevated serum ALT activity. Searching for the main cause, we found the following groups: I) patients with diseases unrelated to the surgical procedures that cause elevated serum activity; II) patients on pharmacological treatments which may produce transitory elevations of serum ALT activity, and III) patients with elevated serum ALT activity that has no evident clinical or pharmacological cause. The high incidence of patients with this abnormality justified the inclusion of serum ALT activity in the profile. We conclude that: a) the reasons for this elevation should be investigated, b) pediatricians should consider postponing surgery, and c) resumption of normal serum ALT activity should be monitored.

Adolescent↗

Immunohistochemical localization of transforming growth factor-alpha in choroid plexus of the rat and chicken.

Transforming growth factor-alpha (TGF-alpha) is a polypeptide which binds to epidermal growth factor-receptor (EGF-R) to carry out its function. We have observed strong TGF-alpha immunoreactivity in the developing and adult choroid plexus of the rat and chicken and glial cells of adult rats, by using a well characterized monoclonal antibody and the peroxidase method. Preabsortion of the antibody with the peptide gave negative staining. Since previous studies have shown that EGF-R is localized in several brain regions, but not in the choroid plexus, during development and adulthood, it is suggested that TGF-alpha, synthesized in the choroid plexus and transferred to the cerebrospinal fluid, has a role in brain development. TGF-alpha immunoreactivity found in glial cells, but not in neurons of adult rats, suggests that TGF-alpha in adulthood is also synthetized in the glial cell compartment.

Aging↗

The expression of a neuronal nuclear antigen (Ri) recognized by the human anti-Ri autoantibody in the developing rat nervous system.

Anti-Ri is a human autoantibody that recognizes a neuronal nuclear antigen (Ri) of unknown function. To ascertain the possible role of the Ri antigen in neuronal development, we analysed the pattern of the anti-Ri immunoreactivity in the developing rat nervous system. Neurons of the retina, except the photoreceptors, and central but not peripheral nervous system were anti-Ri-positive. The intensity of the immunoreactivity followed the sequence of neuronal maturation. Germinal cells of the periventricular layer and migrating neuroblasts in the intermediate zone were Ri-negative. These data suggest Ri antigen may play a role in the postmigratory maturation of neurons of the CNS.

Animals↗

Distribution, morphological features, and synaptic connections of parvalbumin- and calbindin D28k-immunoreactive neurons in the human hippocampal formation.

Calcium binding proteins calbindin D28k (CaBP) and parvalbumin (PV) are known to form distinct subpopulations of gamma-aminobutyric acid (GABA)ergic neurons in the rodent hippocampal formation. Light and electron microscopic morphology and connections of these protein-containing neurons are only partly known in the primate hippocampus. In this study, CaBP and PV were localized in neurons of the human hippocampal formation including the subicular complex (prosubiculum, subiculum, and presubiculum) in order to explore to what extent these subpopulations of hippocampal neurons differ in phylogenetically distant species. CaBP immunoreactivity was present in virtually all granule cells of the dentate gyrus and population of in a proportion of pyramidal neurons in the CA1 and CA2 regions. A distinct population of CaBP-positive local circuit neurons was found in all layers of the dentate gyrus and Ammon's horn. Most frequently they were located in the molecular layer of the dentate gyrus and the pyramidal layer of Ammon's horn. In the subicular complex pyramidal neurons were not immunoreactive for CaBP. In the prosubiculum and subiculum immunoreactive nonpyramidal neurons were equally distributed in all layers, whereas in the presubiculum they occurred mainly in the superficial layers. Electron microscopy showed typical somatic and dendritic features of the granule, pyramidal, and local circuit neurons. CaBP-positive mossy fiber terminals in the hilus of the dentate gyrus and terminals of presumed pyramidal neurons of Ammon's horn formed asymmetric synapses with dendrites and spines. CaBP-positive terminals of nonprincipal neurons formed symmetric synapses with dendrites and dendritic spines, but never with somata or axon initial segments. PV was exclusively present in local circuit neurons in both the hippocampal formation and subicular complex. Most of the PV-positive cell bodies were located among or close to the principal cell layers. However, large numbers of immunoreactive neurons were also found in the molecular layer of the dentate gyrus and in strata oriens of Ammon's horn. PV-positive cells were equally distributed in all layers of the subicular complex. Electron microscopy showed the characteristic somatic and dendritic features of local circuit neurons. PV-positive axon terminals formed exclusively symmetric synapses with somata, axon initial segments and dendritic shafts, and in a few cases with dendritic spines. The CaBP- and PV-containing neurons formed similar subpopulations in rodents, monkeys, and humans, although the human hippocampus displayed the largest variability of these immunoreactive neurons in their morphology and location. Calcium binding protein-containing neurons frequently occurred in the molecular layer of the human dentate gyrus and in the stratum lacunosum-moleculare of Ammon's horn.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Parvalbumin-immunoreactive dystrophic neurites and aberrant sprouts in the cerebral cortex of patients with Alzheimer's disease.

Parvalbumin-immunoreactive dystrophic neurites and aberrant terminal sprouts associated with senile plaques, together with preserved density of parvalbumin-immunoreactive neurons, were found in the cerebral cortex of two patients with Alzheimer's disease, one of them familiar, in which a biopsy of the left frontal lobe was carried out for diagnostic and counselling purposes. These findings suggest that, although parvalbumin-immunoreactive cells are relatively resistant to degeneration in Alzheimer's disease, parvalbumin-immunoreactive neuronal processes can degenerate in some cases of Alzheimer's disease.

Aged↗

Parvalbumin-immunoreactive cortical neurons in Creutzfeldt-Jakob disease.

Massive abnormalities of parvalbumin-immunoreactive cortical neurons were observed in the cerebral biopsy samples of 3 patients with Creutzfeldt-Jakob disease. Immunoreactive cells had reduced and short, often fragmented, dendrites, and large numbers of dendritic varicosities were observed. Since parvalbumin-immunoreactive neurons are the most important inhibitory cells in the cerebral cortex, the damage to these neurons may account, in part, for the impaired cortical function, and may play a role in the appearance of myoclonus and electroencephalographic patterns in patients with Creutzfeldt-Jakob disease.

Cerebral Cortex↗

Polyclonal 111In-IgG, 125I-LDL and 125I-endothelin-1 accumulation in experimental arterial wall injury.

To test iodine-125 labelled low-density lipoprotein (125I-LDL), polyclonal indium-111 labelled immunoglobulin G (111In-IgG) and iodine-125 labelled endothelin-1 uptake in metabolically active atheromatous plaques after arterial wall injury, we performed balloon de-endothelialization of carotid arteries or abdominal aortas in 24 New Zealand male rabbits which were fed with a normal diet (n = 14) or a hypercholesterolaemic diet (n = 10) after surgery. Six weeks later the animals were injected with 200 microCi of 125I-LDL and/or with 100 microCi of 111In-IgG or with 9 microCi of 125I-endothelin-1. Forty-eight hours later the animals were sacrificed. Carotid arteries and aortas were removed, counted and fixed for autoradiography and light microscopy examination. Contralateral carotid arteries and thoracic aortas served as controls. Significant 111In-IgG uptake was observed in the injured arteries at autoradiography, with localization mainly in the healing edges, and at well counting. The percentage of the injected dose per gram (%D.inj/g) was 0.0188 +/- 0.06 versus 0.0059 +/- 0.003 in controls (P < 0.05). There was no difference in 111In-IgG uptake between arteries with injury alone and those with active atheroma formation at the site of the injury. Significant 125I-LDL uptake was observed only when lipid deposition was present at light microscopy (%D.inj/g of 0.0024 +/- 0.0005 vs. 0.0010 +/- 0.0003 in controls, P < 0.05). 125I-endothelin-1 accumulation was observed in four of five injured aortas both at autoradiography, with diffuse localization, and at well counting (%D.inj/g of 0.0012 +/- 0.0004 in the abdominal aortas vs 0.0008 +/- 0.0003 in the thoracic aortas).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Postnatal development of parvalbumin and calbindin D28K immunoreactivities in the cerebral cortex of the rat.

Parvalbumin and calbindin D28k immunoreactivities were examined in the neocortex of the rat during postnatal development. Parvalbumin-immunoreactive nonpyramidal neurons first appear in layer V and later in layers VI and IV, and then in II and III. Immunoreactive terminals forming baskets surrounding unlabelled somata appear about 2 days later. The first parvalbumin-immunoreactive neurons appear in the retrosplenial and cingulate cortices, and the rostral region of the primary somatosensory cortex at postnatal days 8 or 9 (P8-P9). These regions are followed by the primary visual, primary auditory and motor cortices at P11. Parvalbumin immunoreactivity appears last in the secondary areas of the sensory regions and association cortices. Adult patterns are reached at the end of the 3rd week. Calbindin D28K-immunoreactive nonpyramidal neurons are found at birth in all cortical layers excepting the molecular layer. The intensity of the immunoreaction increases during the first 8 or 11 days of postnatal life, first in the inner and later in the upper cortical layers, following, therefore, an "inside-out" gradient. Heavily-labelled calbindin D28K-immunoreactive nonpyramidal cells dramatically decrease in number from P11 to P15 due mainly to a decrease of the multipolar subtypes. This suggests that two populations of calbindin D28k-immunoreactive nonpyramidal neurons are produced in the neocortex during postnatal development: one population of neurons transitorily expresses calbindin D28k immunoreactivity; the other population is composed of neurons that are permanently calbindin D28k immunoreactive. In addition to heavily labelled nonpyramidal cells, a band of weakly labelled pyramid-like neurons progressively appears in layers II and III throughout the cerebral cortex, beginning in layer IV in the somatosensory cortex by the end of the 2st week. Adult patterns are reached at the end of the 3rd week. These results indicate that parvalbumin and calbindin D28k immunoreactivities in the cerebral neocortex follow different characteristic patterns during postnatal development. The appearance of parvalbumin immunoreactivity correlates with the appearance of the related functional activity in the different cortical regions, and, probably, with the appearance of inhibitory activity in the neocortex. On the other hand, the early appearance of calbindin D28k immunoreactivity in the neocortex may be related to the early appearance of calbindin immunoreactivity in many other brain regions, and suggests another, as yet unknown, role for this calcium-binding protein during development of the cerebral cortex.

Animals↗