Biomedical subjects

I Ferrer

Publications and source records attributed to I Ferrer.

At least 235 records · Page 13Linked to original sources

PubMed1995

Hereditary spastic paraparesis with dementia, amyotrophy and peripheral neuropathy. A neuropathological study.

Hereditary, probably autosomal recessive, spastic paraparesis in two siblings was associated with dementia of frontal lobe type, amyotrophy and peripheral sensory and motor polyneuropathy. Neuropathological findings correlate with neurological deficits, although neuron loss in the caudate and putamen, substantia nigra, and loss of Purkinje cells were clinically silent. Loss of neurons occurred in all cortical layers of the prefrontal lobe and superior temporal gyrus. Immunohistochemical studies showed reduced parvalbumin immunoreactivity in dendrites, and reduced numbers of calbindin D28k-immunoreactive cells, thus suggesting involvement of cortical local-circuit neurons. Myelin loss, ubiquitin-immunoreactive granular deposits, and nerve fibre degeneration in the white matter of the frontal lobes and corpus callosum were also observed. Cerebral and subcortical white matter abnormalities, together with atrophy of the thalamic dorsomedial complex and anterior nucleus, may have accounted for the development of severe dementia in this patient.

Brain↗

PubMed1995

Clinical, neuropathologic, and genetic studies of a large spinocerebellar ataxia type 1 (SCA1) kindred: (CAG)n expansion and early premonitory signs and symptoms.

We report the clinical, neuropathologic, and genetic studies of a large kindred (family M-ADCA1) with autosomal dominant spinocerebellar ataxia type 1 (SCA1), ascertained in 41 members, with clinical data available in twenty-two. The mean age of onset was 36.3 +/- 6.2 years (ages, 26 to 52), the mean duration of the disease was 15.8 +/- 6.5 years (range, 10 to 28 years), and the mean age at death was 54.1 +/- 9.5 years (ages, 39 to 72). Premonitory signs and symptoms appeared earlier than the usual onset symptoms in many of the clinically unaffected patients who inherited the mutated SCA1 gene. Anticipation was present when we compared the seventh and eighth generations. A more severe course of the disease occurred in offspring of affected males. Neuropathologic examination, performed on three patients, showed the usual findings of SCA1; Golgi and immunocytochemistry studies suggested primary damage of the Purkinje cells. We analyzed the CAG-repeat mutation responsible for the SCA1 phenotype in a total of 41 family members. There was expansion in 19 subjects (10 clinically affected, seven with early signs and symptoms, and two asymptomatic individuals), and all showed heterozygosity, with one allele between 41 and 59 repeats (SCA1 mutation) and the other in the range of 6 to 39 repeats (normal range). The clinical analysis of "at risk" patients with the SCA1 mutation showed that minor signs and symptoms begin before full clinical diagnosis, and these premonitory manifestations can herald full development of SCA1 by years.

Adult↗

PubMed1995

Cytomegalovirus ventriculoencephalitis in AIDS patients.

We report 4 autopsy-proven cases of cytomegalovirus ventriculoencephalitis (CMV-VE) and a further case with dramatic clinical and radiological response to ganciclovir therapy. The diagnoses were based upon clinical features, cerebrospinal fluid (CSF) examination and either brain computerized tomography (CT) or magnetic resonance imaging (MRI), and confirmed by autopsy findings in 4 cases. All patients had previously had an AIDS-defining condition. CMV retinitis was diagnosed in 3 patients, 2 of them before the onset of encephalitis. CMV viremia was present in 4 patients. Examination of CSF demonstrated elevated protein and hypoglycorachia in all cases. CSF culture was negative for CMV in 3 of 3 patients. Periventricular enhancement was detected by MRI in 2 of 3 patients, but in only 1 of 5 patients by CT. Three patients received ganciclovir and 2 patients foscarnet therapy. All 4 patients died. Pathologic examination revealed periventriculitis with ependymal necrosis and CMV intranuclear inclusion bodies all 4 patients. One showed a marked neurological improvement and radiological resolution by MRI after 4 weeks of ganciclovir therapy. We conclude that CMV-VE should be suspected in HIV-infected patients who present with altered neurological status, CMV viremia or retinitis, hypoglycorachia and ventriculitis as demonstrated by MRI. Although more effective therapy is needed, ganciclovir may be beneficial, as shown in one of our patients.

AIDS-Related Opportunistic Infections↗

PubMed1995

Cell death induced by gamma irradiation of developing skeletal muscle.

Newborn Sprague-Dawley rats were exposed to a single dose of 2 Gy gamma rays and killed from 6 h to 5 d later. Increased numbers of dying cells, characterised by their extreme chromatin condensation and often nuclear fragmentation were seen in skeletal muscle 6 h after irradiation. Dying cells decreased to nearly normal values 48 h later. In situ labelling of nuclear DNA fragmentation identified individual cells bearing fragmented DNA. The effects of gamma rays were suppressed following cycloheximide i.p. at a dose of 1 microgram/g body weight given at the time of irradiation. Taken together, the present morphological and pharmacological results suggest that gamma ray induced cell death in skeletal muscle is apoptotic, and that the process is associated with protein synthesis. Finally, proliferating cell nuclear antigen-immunoreactive cells, which were abundant in control rats, decreased in number 48 h after irradiation. However, a marked increase significantly above normal age values was observed at the 5th day, thus suggesting that regeneration occurs following irradiation-induced cell death in developing muscle.

Animals↗

PubMed1994

Ubiquitinated structures in the white matter of the gerbil following chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion was produced in adult gerbils aged 3-6 months following bilateral stenosis of the carotid artery lasting 8 weeks. Animals with no evidence of cerebral infarction were used in the present study. Ubiquitin-immunoreactive free granules in the subcortical cerebral white matter and corpus callosum were observed in five of 12 animals. No similar lesions were found in sham-operated animals, age-matched controls, and gerbils subjected to transient forebrain ischaemia for 20 min and killed at different intervals. These results indicate that diffuse damage of the subcortical white matter may be encountered as the only neuropathological change following chronic hypoperfusion.

Animals↗

PubMed1994

Early 72-kDa heat shock protein induction in microglial cells following focal ischemia in the rat brain.

Focal cerebral ischemia in the adult rat produces induction of 72-kDa heat shock protein (HSP-72) in neurons, glia and endothelial cells. Double antigen immunocytochemistry was carried out to find out whether microglial cells express HSP-72 following 1-h middle cerebral artery (MCA) occlusion. A monoclonal antibody against the CR3 complement receptor (OX-42) specific for microglia was used followed by a monoclonal antibody against HSP-72. Co-localization of these antibodies was seen in cells of the ipsilateral corpus callosum and striatum at 3 h following 1-h MCA occlusion, and in the ipsilateral striatal penumbra, corpus callosum and cortex at 8 h. Results demonstrate that stellate microglial cells show an early response to 1-h MCA occlusion by expressing inducible HSP-72, thus suggesting that microglial cells are sensitive to the ischemic insult.

Animals↗

PubMed1994

Naturally occurring cell death in the developing cerebral cortex of the rat. Evidence of apoptosis-associated internucleosomal DNA fragmentation.

Naturally occurring dead cells in the developing rat neocortex, subcortical white matter and hippocampus, which increase in number during the first postnatal week and decrease thereafter to disappear by the end of the first month, were examined by in situ labeling of nuclear DNA fragmentation. These cells showed peripheral chromatin condensation or extremely dark, often fragmented, nuclei. Southern hybridization following agarose gel electrophoresis of DNA extracted from the developing cortex, but not from adult brain, showed a 'ladder' pattern which is typical of internucleosomal DNA fragmentation. Taken together these results show that naturally occurring cell death (programmed cell death) in the developing cerebral cortex has the morphology of apoptosis and is associated with endonuclease activation.

Aging↗

PubMed1994

Kainic acid inhibits protein amino acid incorporation in select rat brain regions.

Regional incorporation of labelled methionine into proteins was studied with quantitative autoradiography in different regions of the rat brain 2.5 h following systemic kainic acid administration. Labelled protein concentration was found reduced to approximately 40% of control values in the pyramidal cell layer of hippocampus, piriform, entorhinal and perirhinal cortices, ventral lateral septum and mediodorsal thalamic nucleus. These regions showed increased levels of label not incorporated into proteins, indicating that free labelled methionine was available for protein synthesis. Reduction of protein amino acid incorporation in those brain regions selectively affected by kainic acid may be involved in subsequent tissue damage.

Amino Acids↗

PubMed1994

Postnatal development of parvalbumin immunoreactivity in the cerebral cortex of the cat.

Parvalbumin immunoreactivity in the developing neocortex of the cat progresses following specific laminar, areal, and, in a particular area, roughly anteroposterior gradients. Parvalbumin immunoreactivity first occurs in basket cells and later in chandelier neurons. Pyramid-like immunoreactive neurons are also transitorily observed from the second to the third week in layer V of the auditory association-related areas. Parvalbumin-immunoreactive neurons first appear in the primary somatosensory cortex and primary auditory and visual areas, followed by the primary motor and polysensory association areas and, finally, the auditory association areas and cortical areas related to the limbic system. In addition to cortical neurons, three fiber systems are immunolabeled with antiparvalbumin antibodies: thalamocortical, callosal, and ipsilateral corticocortical. Parvalbumin-immunoreactive thalamocortical fibers appear during the first month of postnatal life. Parvalbumin-immunoreactive callosal and ipsilateral corticocortical fibers are seen from the fourth postnatal week onward. Because all parvalbumin-immunoreactive cortical neurons in adulthood are nonpyramidal inhibitory cells, the present findings suggest that a number of ipsilateral corticocortical and callosal connections may be inhibitory.

Aging↗

PubMed1994

Increased expression of bcl-2 immunoreactivity in the developing cerebral cortex of the rat.

Bcl-2 proto-oncogene encodes a protein which may cancel the cell death programme in normal development and experimentally induced conditions. Strong bcl-2 immunoreactivity occurs in the neocortex and hippocampus of the developing rat during the 1st postnatal week. Bcl-2 immunoreactivity rapidly decreases from this age onwards to steady very low levels in adulthood. Since increased expression of bcl-2 immunoreactivity during cortical neurogenesis is coincidental in time with a special vulnerability of cortical neurons to naturally occurring cell death, it is suggested that bcl-2 may have a role in regulating cell death and survival during cortical morphogenesis.

Animals↗

PubMed1994

The development of parvalbumin-immunoreactivity in the neocortex of the mouse.

In the present study the postnatal development of parvalbumin-immunoreactivity was examined in the neocortex of the mouse. Postnatal mice were processed at different developmental stages using a well-characterized monoclonal antibody against parvalbumin, and immunocytochemistry. The first immunoreactive neurons appeared in the first parietal and retrosplenial cortices at postnatal day 10 (P10). From P11 to P12, immunoreactivity emerged in the second parietal, cingular, frontal, hindlimb-forelimb, first temporal, primary and secondary occipital and gustatory cortices, and at P14, parvalbumin-positive cells were present in the remaining regions. In general, parvalbumin-immunoreactivity appeared first in the primary sensory/motor areas, and then in second sensory/motor or associative areas. The maturation of parvalbumin-immunoreactivity, however, was a long-lasting process, which was not completed until adult stages. In all cortical regions, parvalbumin-immunoreactive cells were present first in layer V, from which immunoreactivity expanded to the upper and inner cortical layers at subsequent developmental stages. This pattern of maturation differed from the usual 'inside-out' gradient of neocortical neurogenesis and maturation. At the cellular level, parvalbumin-immunoreactivity appeared first in cell somata, and staining of dendrites and boutons was apparent two days later. From the second postnatal week onwards, an immunoreactive axonal system was observed in the neocortical white matter and the corpus callosum. We conclude that the emergence and maturation of parvalbumin-immunoreactivity in the mouse neocortex shows marked area-specific differences, but proceeds following a similar center-to-outside radial gradient. These features may reflect the acquisition of certain physiological properties by a subset of GABAergic inhibitory neurons.

Animals↗

PubMed1994

Induction of HSP70 mRNA and HSP70 protein in the hippocampus of the developing gerbil following transient forebrain ischemia.

The effects of a 20-min transient episode of forebrain ischemia on the induction of HSP70 mRNA and protein, and the histopathological outcome in the hippocampus of the developing gerbil, were examined at postnatal days (P) 7, 15, 21 and 30 and in adulthood. 4 days after the ischemic episode, P7 gerbils did not show apparent histological abnormalities; however, from P15 onwards, ischemia resulted in necrosis in selected areas of the hippocampus. At P15 and P21, necrosis was observed in the base of the granular cell layer of the dentate gyrus and in the CA3 pyramidal cell layer, whereas at P30 and adult necrosis was apparent in the CA1 pyramidal cell layer. HSP70 mRNA induction was not found in ischemic P7 and P15 gerbils while, from P21 onwards, induction was observed in the dentate gyrus and CA1 pyramidal cell layer. In addition, at P30 and adult, HSP70 mRNA expression was also seen in CA3 pyramidal cell layer. Induction of HSP70 immunoreactivity was not seen at P7 but, from P15 onwards, ischemia induced HSP70 immunoreactivity in different areas: in dentate gyrus granular and molecular layers, from P15 onwards; in CA1 pyramidal cell layer, from P21 onwards; and in CA3 pyramidal cell layer, from P30 onwards. Results show selective age-dependent patterns of vulnerability to ischemia in the gerbil hippocampus which, overall, were not well-correlated to the corresponding HSP70 mRNA and protein induction patterns.

Aging↗

PubMed1994

Parvalbumin immunocytochemistry and calcium deposition in muscle fiber necrosis and subsequent regeneration following intramuscular injection of metoclopramide.

We have studied the sequential change of parvalbumin immunocytochemistry and its correlation with intracellular Ca2+ deposition in an animal model of muscle fiber necrosis and regeneration induced by intramuscular injection of metoclopramide. Twenty-four hours after the drug's injection, extensive muscle fiber necrosis, together with dramatic loss of parvalbumin immunoreactivity and intracellular Ca2+ deposition, was observed. Muscle fiber regeneration began on day 4 after the injection and was complete by the end of the third week. Parvalbumin was not detected in the regenerating fibers, but gradually emerged during the second week as muscle fibers increased in size. It can be suggested that loss of parvalbumin in necrotic fibers is secondary to the loss in integrity of the sarcolemma. Alternatively, loss of parvalbumin in degenerating fibers may impair calcium buffering and act as a contributory factor in the necrotic process. The progressive appearance of parvalbumin immunoreactivity in regenerating fibers parallels that found in normal myogenesis.

Animals↗

PubMed1994

Postnatal development of parvalbumin immunoreactivity in striated muscles of the rat.

The presence of parvalbumin, a calcium-binding protein, has been correlated with the maturation of locomotor activity in developing striated muscle. In the present study, postnatal parvalbumin immunoreactivity is examined in the tibialis anterior, intercostal, diaphragm and intrinsic muscles of the tongue of the rat to gather a better understanding of the different developmental patterns. Parvalbumin immunoreactivity appears in the anterior tibialis muscle by day 4, and reaches an adult checkerboard pattern 2 days later. In contrast, parvalbumin immunoreactivity in the intrinsic muscles of the tongue, and in diaphragm and intercostal muscles, which are active near birth, does not appear until the 2nd week. Therefore, these features suggest that parvalbumin immunoreaction is not exclusively dependent on functional activity. In addition, the finding that differences in parvalbumin expression do not correlate in time with the differentiation of fiber types as judged by myosin ATPase activity, suggests that myosin and parvalbumin might be regulated by different mechanisms.

Adenosine Triphosphatases↗

PubMed1994

Poor correlation between delayed neuronal death induced by transient forebrain ischemia, and immunoreactivity for parvalbumin and calbindin D-28k in developing gerbil hippocampus.

In the normal developing hippocampus of the gerbil, parvalbumin-immunoreactive neurons first appear in the stratum pyramidale of CA3 at postnatal day 15 (P15), and in CA2 and hilus of the dentate gyrus from P21 onwards. Immunoreactive terminals also follow the same sequence from CA3 to CA1 to reach adult patterns by the end of the 1st month. Calbindin D-28k immunoreactivity is seen in the external part of the upper blade of the dentate gyrus at P5, and progresses to the granule cell and molecular layers of the whole gyrus by P15, except for a thin band of immature cells located at the base of the granule cell layer which are calbindin negative. Calbindin immunoreactivity in mossy fibers progresses from the external to the hilar region of CA3 during the same period. A few immunoreactive cells are also found in the stratum radiatum/lacunare of the CA3, but no calbindin-immunoreactive cells are observed in the CA1 and CA2 subfields. The adult pattern of calbindin immunoreactivity is reached at P21. Vulnerability following transient forebrain ischemia for 20 min was examined in the hippocampal formation of gerbils during postnatal development. No cellular damage was seen in animals aged 7 days. Dying cells were observed at the base of the granule cell layer of the dentate gyrus in animals aged 15, 21 and 30 days. Pyramidal cells in the CA3 subfield were also sensitive to ischemia in gerbils aged 15 days, and less frequently in animals aged 21 days. The adult pattern of cellular damage, characterized by selective vulnerability of the CA1 subfield, was seen from day 30 onwards.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Dose-related effects of cycloheximide on delayed neuronal death in the gerbil hippocampus after bilateral transitory forebrain ischemia.

Degeneration of dendrites followed by punctate chromatin condensation in the CA1 area of the hippocampus is a characteristic of delayed neuronal death following bilateral forebrain ischemia. The effects of the protein synthesis inhibitor cycloheximide on delayed neuronal death following 20 min of bilateral forebrain ischemia were examined in the gerbil hippocampus at the 4th day of reperfusion. Low doses of cycloheximide beginning 10 min after ischemia (1.0 microgram/g body weight in saline followed by 1.0 microgram/g every 24 h) reduced the number of dying cells in the CA1 area, whereas high doses (2.0 micrograms/g, followed by 1.0 microgram/g every 12 h) increased the number of dying cells. No effects were seen when a single dose of cycloheximide was injected 1 h before ischemia. These results indicate that the effects of cycloheximide are dose-dependent, low doses reduce, high doses increase cell death. These findings also indirectly suggest that protein synthesis may play a role in the extent of delayed neuronal death. Some involved proteins could be heat shock proteins, which are induced after ischemia and had been correlated with increased resistance to injury. However, changes of heat shock immunoreactivity in the postischemic hippocampus were not seen in the present study following cycloheximide injection.

Animals↗

PubMed1994

Parvalbumin and calbindin-D28k immunocytochemistry in human neocortical epileptic foci.

Serial sections of cortical resection of 30 patients suffering from drug-resistant epilepsy were processed for parvalbumin and calbindin-D28k immunocytochemistry to determine local circuit neuron populations. Our findings indicate that there is not a simple mechanism to explain neocortical epileptic foci. On the basis of the present results it can be suggested that: (1) reduced percentage of local circuit neurons in the vicinity of neoplasms may account for a decreased intracortical inhibition. (2) Abnormal morphology and distribution of local circuit neurons may result in abnormal cortical inhibition in patients with focal cortical dysplasia, and, probably, in other focal migrational disorders, including neuronal nests in the white matter. (3) Increased percentages of immunoreactive local circuit neurons and fibers in focal neocortical necrosis (cavernous angiomas), diffuse hypoxic encephalopathy, and hippocampus in patients with temporal lobe epilepsy due to mesial sclerosis, may play a role in epilepsy. These neurons can be activated by reduced excitatory inputs, or they may establish abnormal synaptic contacts with other inhibitory neurons. (4) Lack of consistent morphologic abnormalities in the neocortex of patients with temporal lobe epilepsy, and in patients with cryptogenetic frontal lobe epilepsy, suggests that electrically abnormal neocortical foci in these cases are probably epiphenomena.

Adolescent↗

PubMed1994

Regional expression of inducible heat shock protein-70 mRNA in the rat brain following administration of convulsant drugs.

Expression of inducible heat shock protein-70 mRNA (hsp-70 mRNA) was studied in the rat brain following systemic administration of different convulsant agents: an L-type voltage-dependent calcium channel agonist, (+/-)-BAY K 8644 (BAY-K); the excitotoxic glutamate agonists kainic acid and N-methyl-D-aspartic acid (NMDA); and the GABAA receptor complex antagonists pentylenetetrazole (PTZ) and lindane (gamma-hexaclorocyclohexane). BAY-K induced minimal hsp-70 mRNA expression in the hippocampus of convulsant rats, localized in the dentate gyrus and the pyramidal cell layer of Ammon's horn. Kainic acid treatment in rats, showing severe limbic convulsions, caused intense expression of hsp-70 mRNA and protein (HSP-70). Expression was localized in select cerebral regions, notably the pyramidal cell layer of the hippocampal CA3 field of Ammon's horn and the piriform cortex, and also the subicular complex and the amygdala, and, to a lesser extent, the entorhinal cortex, the pyramidal cell layer of CA1, several thalamic nuclei, and the parietal cortex. In contrast, systemic administration of NMDA, PTZ or lindane led to no detectable induction of hsp-70 mRNA in the rat brain, despite producing convulsions. Histological examination revealed cell injury only following kainic acid treatment. Damage was most apparent in the piriform and entorhinal cortices, pyramidal cell layer of the CA1 field, and cortical amygdaloid nuclei. BAY-K, NMDA, PTZ and lindane did not lead to any observable histopathological changes. These results show that convulsions of different aetiology do not inevitably induce hsp-70 mRNA expression or cell damage. Intense expression of hsp-70 mRNA was generally associated with regions that later showed variable degrees of nerve cell damage, although hsp-70 mRNA expression was not always predictive of subsequent cell death or survival.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗