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Biomedical subjects

I Ferrer

Publications and source records attributed to I Ferrer.

At least 271 records · Page 15Linked to original sources
PubMed1993

Structure and pathogenesis of cortical nodules induced by prenatal X-irradiation in the rat.

Segmentation of the cerebral cortex with formation of nodules, predominating in the upper cortical levels, was found in the rat after 200 cGy X-ray exposure at embryonic days 15, 17 or 19. Nodules were composed of pyramidal and nonpyramidal neurons occupying normal positions at different levels of the cerebral cortex as revealed with parvalbumin and calbindin D-28k immunocytochemistry. The nodules, which were large in animals irradiated at embryonic day 15 but reduced to groups of a few cells in rats irradiated at embryonic day 19, were separated by low cell density zones. Autoradiographic studies using tritiated methylthymidine injections given to pregnant irradiated rats at different days of gestation further demonstrated a preserved inside-out gradient of cortical neurogenesis in this cortical malformation. Morphological studies of irradiated embryos disclosed that groups of dead cells were separated by patches of preserved cells in the germinal layer 6 h after irradiation. Columns of migrating neuroblasts separated by low cell density zones were seen 24 h later. These features suggest that cortical nodules observed after prenatal X-irradiation were the result of multifocal cell death in vulnerable (at the moment of X-ray exposure) proliferative units of the germinal neuroepithelium, combined with normal neurogenesis and migration of neuroblasts from the preserved germinal zones. These findings also suggest that cell proliferation is not uniform through the germinal layer but occurs synchronously in alternate proliferative units. These proliferative units probably co-generate pyramidal and nonpyramidal cells.

Animals↗
PubMed1993

Radiosensitive populations and recovery in X-ray-induced apoptosis in the developing cerebellum.

Sprague-Dawley rats received a single dose of 2 Gy X-rays at the age of 1 or 3 days and were killed at different intervals. Dying cells with the morphological characteristics of apoptosis appeared in the external and internal granular layers (EGL and IGL) and white matter (WM) of the cerebellum, mainly 3-6 h after irradiation, and decreased thereafter to reach normal values between 48 h and 5 days later. This process was curbed by the injection of cycloheximide at a dose of 1 microgram/g body weight. In addition, the number of mitoses in EGL rapidly decreased after irradiation and did not reach normal values until a few days later. Proliferating cell nuclear antigen (PCNA)-immunoreactive cells, which were chiefly found in EGL but also in IGL and WM, dramatically decreased in number from 3 to 48 h after irradiation. PCNA-immunoreactive cells reappeared and reached age-matched values in the following days. Hu (considered as an early neuronal marker) and vimentin immunocytochemistry disclosed that Hu-nonreactive cells in the upper level of EGL, Hu-immunoreactive cells in the inner level of EGL, Bergmann glia and many astrocytes in WM, as well as many non-typified cells in WM, were radiosensitive populations, whereas Purkinje cells were not. The present results indicate that irradiation at P1 or P3 blocks mitosis in EGL and kills sensitive cells mainly in the late G1 and S phases of the cell cycle, probably by apoptosis through a protein synthesis-mediated process. Radiosensitive cells are germinal cells and neuroblasts in EGL, Bergmann glia, astrocytes in WM, and non-typified cells, probably glial cell precursors, in WM. Surviving cells in EGL and PCNA-immunoreactive cells in other cortical layers and white matter reconstitute the cerebellum following a single dose of X-rays.

Animals↗
PubMed1993

Experimentally induced laminar necrosis, status verrucosus, focal cortical dysplasia reminiscent of microgyria, and porencephaly in the rat.

Different types of cortical malformation were produced, following focal cortical freezing, electrocoagulation, focal cortical aspiration or gentle brushing of uncovered meninges, in newborn or 1- to 3-day-old rats. Malformations included laminar necrosis of the cerebral cortex, status verrucosus, focal cortical dysplasia reminiscent of microgyria, and porencephaly. Similar procedures from postnatal day 4 onwards, at a time when a reactive astrogliosis is possible, produced cavitating infarcts and tissue scars. Cytoarchitectonic studies revealed an abnormal distribution of different types of pyramidal and non-pyramidal neurons in these malformations. These indicated three subtypes of focal cortical dysplasia, which probably depend on different pathogenic mechanisms. Autoradiographic studies with [3H] methylthymidine showed normal positioning of late-generated neuroblasts in the cerebral cortex, thus suggesting preserved migration. The present experimentally induced cortical malformations are useful models of similar cortical abnormalities in humans.

Animals↗
PubMed1993

Experimentally induced cortical malformations in rats.

Different cortical malformations were produced in rats by a single dose of X-rays (200 cGy) given on different days during gestation. These include large cortical ectopic masses after irradiation on day 14; segmentation of the cerebral cortex following irradiation on days 15, 17, 19; and a four-layered "lissencephalic" cortex following irradiation on day 16. Other types of cortical malformation were produced in rats aged 0-2 days by one of the following procedures: focal cortical freezing, focal electrocoagulation, cortical aspiration, and focal brushing of the meninges with a blunt needle covered with cotton. These latter abnormalities include laminar necrosis of layer V, focal cortical dysplasia reminiscent of microgyria, status verrucosus deformis and porencephaly. Experimentally induced cortical malformations in rats can help to increase our understanding of normal and abnormal neurogenesis and organisation of the human cerebral cortex.

Animals↗
PubMed1993

Primary central white matter degeneration in old dogs.

Degeneration of the central white matter is described in old dogs. The presence of ubiquitin-immunoreactive free granules and intracytoplasmic globules in glial cells and macrophages, together with galacerebroside-immunoreactive precipitates and lipofusion storage, point to the likelihood of a primary myelin degeneration with deposits of non-degraded ubiquitin-protein conjugates and complex galactolipids.

Aging↗
PubMed1993

Controlled diet in phenylketonuria may cause serum carnitine deficiency.

Serum carnitine levels may be reduced in patients with phenylketonuria (PKU) owing to low carnitine intake, deficient carnitine synthesis and acylcarnitine production from phenylalanine metabolites. In order to investigate the possible carnitine deficiency we determined serum carnitine in its different forms and the precursors and cofactors involved in its synthesis in a group of patients with PKU or hyperphenylalaninaemia. Free, total and acylcarnitine values were significatively reduced only in PKU patients with Phe-restricted diet which had not been supplemented with carnitine. Acylcarnitine/free carnitine ratio and all the other parameters studied were normal in all patients. We conclude that the low serum carnitine levels in PKU patients with a strict diet are a consequence of the low carnitine intake.

Adolescent↗
PubMed1993

Neuronal ectopic masses induced by prenatal irradiation in the rat.

Ectopic neuronal masses below the subcortical white matter were seen in the brains of postnatal rats after 200 cGy irradiation at embryonic day 14. In contrast with the laminated organisation of the cortex located above the subcortical white matter, the ectopic masses were formed of confluent nodules composed of pyramidal and non-pyramidal neurons distributed at random, with no laminar organisation. Afferent and efferent fibres to/from the ectopic masses running together with fibres passing the subcortical white matter indicated that the ectopic masses were heavily connected to neighbouring structures. Examination of irradiated embryos revealed that the ectopic masses originated from ectopic periventricular rosettes, composed of germinal cells, which were formed shortly after irradiation. Neuronogenesis in these rosettes did not follow an inside-out gradient, as seen in the laminated cortex; however, early-generated neurons predominated in the external regions, whereas late-generated neurons were mainly located in the middle and internal regions of the ectopic masses.

Animals↗
PubMed1993

Paraneoplastic intestinal pseudo-obstruction associated with high titres of Hu autoantibodies.

Anti-Hu autoantibodies in high titres, as revealed with immunocytochemistry and Western blot, were present in a patient with gastrointestinal pseudo-obstruction and small-cell lung cancer (SCLC) bearing the Hu antigen. Marked neuron and nerve fibre loss were found in the myenteric plexus at postmortem. These findings show that neuronopathic Hu-associated gastrointestinal pseudo-obstruction can occur as the only paraneoplastic neurological symptom in patients with SCLC.

Antibodies, Neoplasm↗
PubMed1993

Proto-oncogene c-fos induction in thiamine-deficient encephalopathy. Protective effects of nicardipine on pyrithiamine-induced lesions.

Treatment of rats with the central thiamine antagonist, pyrithiamine, results in severe neurological symptoms such as ataxia and convulsions. Induction of proto-oncogene c-fos expression, often related to seizure activity, has been detected in the brains of thiamine-deficient rats by means of Northern blot analysis and in situ hybridization. Region-selective increases of lactate observed following thiamine deficiency development are largely coincident with histologically vulnerable regions. When thiamine-deficient rats were treated with the calcium channel blocker, nicardipine, lesions associated with thiamine deficiency did not appear and there was no induction of c-fos mRNA expression. This suggests a neurocytoprotective role of nicardipine to neuronal cell damage in thiamine-deficient encephalopathy.

Animals↗
PubMed1993

Fructose-1,6-bisphosphate fails to ameliorate delayed neuronal death in the CA1 area after transient forebrain ischaemia in gerbils.

Fructose-1,6-bisphosphate has been shown to reduce ischaemic-induced brain damage in rabbits and gerbils. In view of these findings, we investigated the effects of fructose-1,6-bisphosphate on delayed neuronal death, following bilateral forebrain ischaemia, in the gerbil hippocampus at the fourth day of reperfusion. We subjected gerbils to bilateral forebrain ischaemia for 20 min. Fructose-1,6-bisphosphate was administered: intraperitoneally at a dose of 1 g/kg in saline in hr before the occlusion or at a dose of 1 g/kg 1 hr before the occlusion and every 24 hr for 3 days; or intraventricularly at a dose of 0.1 g/kg just after the carotid occlusion. No significant differences in the number of dying cells in the CA1 area were found between each group of treated animals when compared with controls. This study suggests that fructose-1,6-bisphosphate, administered according to these three different schedules, fails to ameliorate delayed neuronal death after 20 min of bilateral forebrain ischaemia in the CA1 area of the gerbil hippocampus.

Animals↗
PubMed1993

Chandelier cell axons identified by parvalbumin-immunoreactivity in the normal human temporal cortex and in Alzheimer's disease.

Parvalbumin is a calcium-binding protein which is thought to play a role in neuronal excitability. In the cerebral cortex parvalbumin is largely found in two subsets of GABAergic neurons, the chandelier and basket cells. A distinguishing characteristic of the chandelier cell is that the terminal portions of its axon form short vertical strings of boutons resembling candlesticks, which embrace the initial segment of pyramidal cell axon. In the present study, the terminals of chandelier cells in the human temporal cortex were immunostained with an antibody against parvalbumin. These terminals were found more abundantly in layers II and VI, less frequently in layers III and V, were hardly identified in layer IV, and absent in layer I. The relationship of parvalbumin-immunoreactive terminals and axon initial segments was further evidenced by re-sectioning identified rows of boutons into semithin sections. Electron microscopy of both temporal cortex and the somatosensory region of a biopsy sample revealed that these parvalbumin-positive boutons indeed form symmetric synaptic contacts on the axon initial segments of pyramidal cells. As part of an enquiry into the possibility that these specialized interneurons may be involved in degenerative neurological diseases, the temporal lobes from seven patients with Alzheimer's disease were immunostained for parvalbumin. As in the control brains, the specific terminal portions of chandelier cells were recognized and identified in the temporal cortex by parvalbumin-immunocytochemistry. No major difference from normal brains was found, excepting for a lower density of candlesticks (30-35%) in layer II-III. Since we showed in a previous study [Ferrer et al. (1991) J. neurol. Sci. 106, 135-141] that the number of parvalbumin-immunoreactive somata in the same Alzheimer's disease cases was not decreased, the observed reduction of terminals in layer II suggest that only the terminals of chandelier cells, but not the parent neurons, are decreased in Alzheimer's disease.

Aged↗
PubMed1993

Parvalbumin immunoreactivity in the hippocampus of the gerbil after transient forebrain ischaemia: a qualitative and quantitative sequential study.

Parvalbumin immunoreactivity is examined in the hippocampus of the Mongolian gerbil (Meriones unguiculatus) in controls and in animals subjected to 20 min of forebrain ischaemia produced by bilateral clipping of the carotids. In comparison with other species, the hippocampus of the gerbil is characterized by strong immunoreactivity of the (presumably excitatory) perforant pathway, and weak immunoreactivity (low numbers of neurons and scarce dendritic arbors) in nonpyramidal nerve cells (inhibitory neurons) of the CA1 area. These properties may play some role in the development and maintenance of seizures in this susceptible species. Parvalbumin immunoreactivity is rapidly and ephemerally increased in the hippocampus 15 min after reperfusion. Later on, there is a transitory decrease of parvalbumin immunoreactivity which is followed by an increase 6 h later in the stratum granulare hilus and CA3 area, and not until the first and second days in the CA1 area. This increase significantly surpasses the number of immunoreactive neurons in control animals in CA1 and CA3 from 48 h after reperfusion onwards. The effect is similar using different anaesthetics and does not occur in sham-operated animals. In contrast with these findings, the number of parvalbumin-immunoreactive neurons in the somatosensory cortex is not affected in our model of forebrain ischaemia. On the other hand, GABA-immunoreactive neurons in CA1 are preserved during the first week after reperfusion, although an increase in the number of these cells occurs at the end of this period. Delayed neuronal death occurs in the CA1 area 48 h after ischaemia, and marked reduction in the number of CA1 neurons is found by the end of the first week. Eighty per cent of the remaining cells in CA1 at day 7, and 83% at day 15, are parvalbumin-immunoreactive nonpyramidal neurons in contrast to 3% parvalbumin-immunoreactive cells in control animals. These findings indicate that GABAergic neurons in CA1 are preserved after forebrain ischaemia, and that parvalbumin in CA1 neurons is associated with survival.

Animals↗
PubMed1993

Cyclic changes in pulmonary wedge v waves in dilated cardiomyopathy.

Right and left cardiac catheterization was performed in a 29-year-old male with dilated cardiomyopathy. During the procedure, prominent v waves appeared spontaneously in the pulmonary capillary wedge pressure recording with a simultaneous decrease in left ventricular systolic pressure. Left ventricular angiography showed moderate to severe mitral regurgitation and an ejection fraction of 22%. The right ventricular endomyocardial biopsy revealed histological findings consistent with dilated cardiomyopathy. Cardiac catheterization was repeated 9 months later, after a period of clinical improvement and a reduction in the right and left ventricular filling pressures was documented. The cyclic swings in the pulmonary capillary wedge pressure and in the left ventricular systolic pressure were not observed. Left ventriculography showed mild mitral regurgitation with an ejection fraction of 37%. Right ventricular endomyocardial biopsy documented a reduction in myofibrillar and nuclear hypertrophy. Thus, cyclic changes in pulmonary wedge v waves may be observed in dilated cardiomyopathy. This finding is consistent with cyclic variations in the degree of mitral regurgitation. Disappearance of this factor seems to be related to improvement in left ventricular contractility.

Adult↗
PubMed1993

X-ray-induced cell death in the developing hippocampal complex involves neurons and requires protein synthesis.

Sprague-Dawley rats aged 1 or 15 days were irradiated with a single dose of 200 cGy X-rays and killed at different intervals from 3 to 48 hours (h). Dying cells were recognized by their shrunken and often fragmented nuclei and less damaged cytoplasm in the early stages. On the basis of immunocytochemical markers, dying cells probably represented a heterogeneous population which included neurons and immature cells. In rats aged 1 day the number of dying cells rapidly increased in the hippocampal complex with peak values 6 h after irradiation. This was followed by a gentle decrease to reach normal values 48 h after irradiation. The most severely affected regions were the subplate and the cellular layer of the subiculum, gyrus dentatus and hilus, and the stratum oriens and pyramidale of the hippocampus (CA1 more affected than CA2, and this more affected than CA3). X-ray-induced cell death was abolished with an injection of cycloheximide (2 micrograms/g i.p.) given at the time of irradiation. X-ray-induced cell death was not changed after the intraventricular administration of nerve growth factor (NGF; 10 micrograms in saline) at the time of irradiation. Cell death was not induced by X-irradiation in rats aged 15 days. These results indicate that X-ray-induced cell death in the hippocampal complex of the developing rat is subjected to determinate temporal and regional patterns of vulnerability; it is an active process mediated by protein synthesis but probably not dependent on NGF.

Aging↗
PubMed1993

A four-layered 'lissencephalic' cortex induced by prenatal X-irradiation in the rat.

A four-layered cortex is produced in the dorsal region of the rat brain, after 200 cGy X-irradiation at embryonic day 16. The layer 1 is the molecular layer; layer 2 is the upper cellular layer which is in continuity with normal layers V and VI in the lateral cortex; layer 3 is a sparsely cellular layer; and layer 4 is the inner cellular layer which is composed of neurons normally committed to the upper cortical layers. This failure of neuroblast migration to the upper layers is associated with reduced numbers, and morphological abnormalities, of radial glial cells in the dorsal cortex. This further supports the idea that abnormal interactions between neuroblasts and radial glial cells result in abnormal migratory patterns. Since a similar four-layered organization is found in human lissencephaly type I, the present results bring new data that can serve our better understanding of human cortical malformations.

Abnormalities, Radiation-Induced↗
PubMed1993

Calbindin D-28k and parvalbumin immunoreactivity in the frontal cortex in patients with frontal lobe dementia of non-Alzheimer type associated with amyotrophic lateral sclerosis.

The morphology and distribution of local-circuit neurons (interneurons) were examined, by calbindin D-28k and parvalbumin immunocytochemistry, in the frontal cortex (area 8) in two patients with frontal lobe dementia of non-Alzheimer type associated with classical amyotrophic lateral sclerosis (ALS), and in seven normal cases. The density of calbindin D-28k immunoreactive cells was dramatically reduced in ALS patients, but the density of parvalbumin-immunoreactive neurons was preserved. Decreased density of calbindin D-28k-immunoreactive neurons, which are mainly located in the upper cortical layers, may interfere with the normal processing of cortico-cortical connections, whereas integrity of parvalbumin-immunoreactive cells may be associated with the preservation of the major inhibitory intracortical circuits in patients with frontal lobe dementia.

Adult↗
PubMed1993

Parvalbumin and calbindin D-28K immunoreactivity in central ganglioglioma and dysplastic gangliocytoma of the cerebellum. Report of two cases.

Calbindin D-28K and parvalbumin immunocytochemistry were used in the study of central ganglionic cell tumors. Most neurons in the ganglioglioma were immunoreactive to calbindin D-28K, but a few cells were labeled with antibodies against parvalbumin. In contrast, most cells in dysplastic gangliocytoma of the cerebellum were parvalbumin immunoreactive, but fewer reacted with anti-calbindin antibodies. These latter cells had two or three dendrites with claw-shaped terminals and axons with recurrent collateral branches and varicose terminals filled with strings and buttons. These observations suggest that central ganglionic cell tumors, including dysplastic gangliocytoma of the cerebellum, are composed of neurons which, on the basis of their calcium-binding protein content, have particular metabolic and electrophysiological properties.

Adolescent↗