PubMed Health⌕ Search

Biomedical subjects

R P Saneto

Publications and source records attributed to R P Saneto.

At least 19 recordsLinked to original sources
PubMed2003

When might hemispheric favouring of epileptiform discharges begin?

PURPOSE: EEG studies based on adult populations report interictal epileptiform discharges (EDS) favour the left hemisphere. It is not clear when favouring becomes apparent as similar paediatric studies have not been performed. METHODS: The authors reviewed 1,579 paediatric EEG interpretations for evidence of hemispheric favouring of focal epileptiform discharges. Analysis focused on first-time EEG results. RESULTS: Right hemispheric favouring of interictal epileptiform discharges occurs in childhood, it remits around 5 years of age whereupon left-sided favouring occurs more frequently (P=0.004, Fisher's Exact). CONCLUSION: Hemispheric vulnerabilities to interictal focal epileptiform activity may display discrete age-related favouring. These findings are discussed in context of normal hemispheric maturation.

Adolescent↗
PubMed2000

Epilepsy surgery in infancy.

Surgery for intractable epilepsy is being offered at progressively younger ages, including infancy. The most common causes of catastrophic epilepsy in very young surgical candidates are focal malformations of cortical development and low-grade tumors. Additional causes include Sturge-Weber syndrome, epidermal nevus syndrome, hemimegalencephaly, and prenatal or perinatal infarction. Many infants manifest with focal seizures, whereas some patients have infantile spasms in the setting of a focal epileptogenic lesion. Video electroencepholography, magnetic resonance imaging, and positron emission tomography are critical investigations to explore surgical options. In small series, the percentage of infants free of seizures after surgery was in the range of 60%. This is similar to that seen after epilepsy surgery in older children, adolescents, and adults. However, larger series with long-term follow up will be important. Furthermore, the extensive procedures required in infants for removal of the epileptogenic developmental lesions entail some risk, and should not be offered in the absence of severe epilepsy. Most infant candidates for epilepsy surgery have significant developmental delay. Few data are available, but anecdotal experience suggests that surgical relief of catastrophic epilepsy may result in resumption of developmental progression. For each infant, the timing of surgery must be carefully considered based on full assessment of the relative risks and benefits, derived from a detailed presurgical evaluation.

Brain↗
PubMed1998

Atypical manifestations of two cases of trisomy 9 syndrome: rethinking development delay.

Trisomy 9 syndrome is characterized by "bulbous" nose, microphthalmia, dislocated limbs, and other anomalies of skeletal, cardiac, genitourinary, and central nervous systems. With the exception of one reported case study, all surviving infants have had severe mental impairment. The prospect of severe mental retardation often overwhelms parents who are faced with prenatal diagnosis of trisomy 9. We report on two new cases of mosaic trisomy 9, both of whom are only mildly developmentally delayed. One patient presented with the distinctive facial appearance, large fontanels, and joint abnormalities. The other had none of the typical congenital abnormalities. However, the patient was found to have a congenital heart defect and hypoplastic left heart syndrome, which to our knowledge has not been reported previously in the trisomy 9 syndrome. When these two patients are added to the published patients with this syndrome, there appears to be a range of manifestations, especially with respect to mental status, which has not fully been recognized.

Abnormalities, Multiple↗
PubMed1996

Acute neurotoxicity of meperidine in an infant.

We report a 6-week-old boy with meperidine neurotoxicity. What distinguished our patient from those previously reported was his minimal exposure to therapeutic doses of meperidine in the setting of normal renal function, and no history of sickle cell anemia, cancer, hepatitis, or cirrhosis. In addition, our patient had no abnormal changes in the electroencephalogram during the event. After only 2 doses of meperidine, he exhibited acute orofacial dyskinesias consisting of tongue thrusting, lip pursing, and facial grimacing combined with prominent flexion of the arms and stiffening of his legs. However, a normal sucking response remained. His symptoms resolved over the next 36 hours and did not respond to naloxone. We believe that this unique presentation of meperidine-induced neurotoxicity may be due to changes in the basal ganglia resulting from perinatal hypoxemia.

Analgesics, Opioid↗
PubMed1990

Expression of beta-nerve growth factor in cultured cells derived from the hypothalamus and cerebral cortex.

Although the synthesis of nerve growth factor (NGF) in brain regions innervated by magnocellular cholinergic neurons of the basal forebrain is well documented, the cell type(s) able to produce NGF in the central nervous system (CNS) remain only partially characterized. Moreover, little is known regarding the ability of brain areas not innervated by magnocellular cholinergic neurons to express NGF protein. The hypothalamus, which controls the endocrine system, is one of such regions. Primary culture of mixed populations of cells from the fetal hypothalamus were used to identify the presence of NGF in this brain area. Immunocytochemistry revealed that hypothalamic oligodendrocytes and a subpopulation of neurons expressed the NGF protein. In contrast, astrocytes were either immunonegative or equivocally stained. To define whether synthesis of NGF is restricted to a particular cell type, cultures of purified astrocytes, oligodendrocyte progenitor (oligoP) cells and neurons were utilized. They were obtained from the neonatal cerebral cortex to ensure an adequate yield of glial cells. Virtually the entire population of cerebral oligoP cells were found to express NGF protein. In contrast, and similar to hypothalamic astrocytes, cerebral type I astrocytes isolated at the same time as oligoP cells exhibited little or no NGF staining. When type I astrocytes were induced to differentiate in the presence of a serumless, chemically defined medium, a subpopulation of the culture became more robustly positive for the NGF protein. Contrasting with these differences in NGF immunoreactivity, Northern analysis of RNA isolated from purified cerebral type I astrocytes, oligoP cells and neurons demonstrated that NGF mRNA was expressed in each of these cell types at approximately the same levels. The results indicate that: (a) when placed in culture, each of the major cell types within the CNS has the capability of transcribing the NGF gene, and (b) despite similar NGF mRNA levels the cellular content of NGF protein is greater in a subpopulation of neurons and in oligodendrocytes than in astrocytes, suggesting differences in NGF post-transcriptional regulation between these cell types. In addition, the presence of NGF in hypothalamic cells suggests that NGF may be involved in the regulation of specific hypothalamic neuronal systems.

Animals↗
PubMed1990

The regulation of proenkephalin expression in a distinct population of glial cells.

The expression of opioid genes was examined in isolated populations of glial cells in primary culture. Northern blot analysis of purified type I astrocytes, oligodendrocytes and mixed oligodendrocyte-type-2-astrocyte lineage cells derived from cerebral cortex demonstrated robust expression of proenkephalin mRNA exclusively in type I astrocytes. The expression of proenkephalin mRNA was stimulated by the beta-adrenergic agonist isoproterenol, and 8-(4-chlorophenyl thio)adenosine 3'-5'-cyclic monophosphate (cpt-cAMP). Both of these compounds regulated a proenkephalin-chloramphenicol acetyltransferase fusion gene transiently transfected into type I astrocytes. HPLC and immunoassay of the cell culture media revealed significant levels of unprocessed proenkephalin secreted by the cell and this secretion was stimulated by isoproterenol and cpt-cAMP. The relatively high levels of proenkephalin expressed suggest that enhanced expression in astrocytes may be important during neural development, in trauma-induced gliosis and in neuroimmune interactions.

Animals↗
PubMed1989

Myelination of axons within cytosine arabinoside treated mouse cerebellar explants by cultured rat oligodendrocytes.

Cell suspensions of cultured purified rat oligodendrocytes prepared by the differential substrate adhesion method were applied to neonatal mouse cerebellar explant cultures in which myelination and oligodendrocyte maturation had been irreversibly inhibited by exposure to cytosine arabinoside. Myelination of Purkinje cell axons within 92% of the host explants was observed 2-5 days after oligodendrocyte application. Ultrastructurally, mature oligodendrocytes and axons surrounded by compact myelin, as well as spherules of compact myelin membranes without axons, were present within the cerebellar explants. It is evident that cultured dissociated purified oligodendrocytes retain the ability to myelinate appropriate axons. Such oligodendrocytes may be hyperreactive with regard to myelin membrane formation, as suggested by the presence of spheres of compact myelin without axons.

Animals↗
PubMed1988

Expression of glial fibrillary acidic protein by differentiated astrocytes is regulated by serum antagonistic factors.

We report here that, in culture, the expression of glial fibrillary acidic protein (GFAP) by astrocytes, as well as their shape (flat-polygonal vs. stellate) can be regulated by 4 serum antagonistic factors. Three of these factors are stimulatory, while the fourth exerts an inhibitory effect upon these astrocytic properties. As suggested by temperature and trypsin treatments, the inhibitory factor is a polypeptide or a protein of 15-35 kDa. The stimulatory factors are smaller: two of them have a mol. wt. between 0.2 and 5 kDa; the third is smaller than 0.2 kDa. Treatments with chloroform/methanol, ammonium sulfate, neuraminidase, and papain, indicate that at least one glycolipid and one glycoprotein are involved. We speculate that, during development, cells from the astrocytic line could be susceptible selectively to one or another of these factors, which would explain their great plasticity.

Animals↗
PubMed1988

Serum contains inducers and repressors of oligodendrocyte differentiation.

An important stage in oligodendrocyte development is the expression of galactocerebroside (GC), the major glycolipid in myelin. Although oligodendrocyte cell lineage and differentiation in vitro have been the object of many studies, to date there is sparse information on the regulation of GC expression in oligodendrocytes already committed to be positive for GC. We report here that GC expression in these cells is controlled by three serum factors. Two of these, possibly a lipoprotein and a mucoprotein, increase GC levels, whereas the third, probably a glycoprotein, exerts an inhibitory effect. The developmental increase of GC in postnatal rat brain cerebral cultures and its induction by serum factors are reversible phenomena. The isolation of the GC-regulatory factors would allow experimental manipulation of impaired GC expression by differentiated oligodendrocytes.

Animals↗
PubMed1987

Interleukin-2 inhibition of oligodendrocyte progenitor cell proliferation depends on expression of the TAC receptor.

Interleukin-2 (IL-2) has been shown to inhibit oligodendrocyte progenitor cell proliferation. Within the immune system, IL-2 biological action is dependent strictly on the expression of the IL-2 receptor. The antibody TAC, which specifically binds the lymphocyte IL-2 receptor, has been shown to also bind oligodendrocyte progenitor cells cultured in a serumless, chemically defined medium. The expression of the TAC antigen was found necessary for IL-2 inhibition of oligodendrocyte progenitor cell proliferation. After IL-2 induced down-regulation of the TAC antigen, the progenitor cell was unresponsive to IL-2, even 72 hr after IL-2 withdrawal. During this unresponsive period, the oligodendrocyte progenitor cell was immunocytochemically negative for the TAC antigen. Thus, in contrast to IL-2 receptors on T-cells, IL-2 does not up-regulate its receptor on oligodendrocyte progenitor cells. However, upon interleukin 1 (IL-1) addition both IL-2 responsiveness and TAC immunocytochemical staining reappeared. These data suggest that IL-2 inhibition of progenitor cell proliferation depends on the expression of the TAC antigen, which can be regulated by IL-1.

Animals↗
PubMed1986

Interleukin 2 mediates the inhibition of oligodendrocyte progenitor cell proliferation in vitro.

In the immune system, T-lymphocyte proliferation depends on interleukin 2 [IL-2 (T-cell growth factor)] interaction with specific receptors. In this study we show that IL-2 can specifically inhibit the proliferation of neonatal rat oligodendrocyte progenitor cells cultured in a serumless, chemically defined medium (oligodendrocyte-defined medium; ODM). IL-2 inhibited both [3H]thymidine incorporation and increase in cell number. Specificity was shown by precipitating IL-2 activity with anti-IL-2 antiserum. Furthermore, growth inhibition depended on the expression of Tac (an anti-IL-2 receptor monoclonal antibody)-positive receptors (IL-2 receptor). When cells were cultured in the presence of IL-2, both Tac-positive staining and growth inhibition were no longer expressed. The addition of interleukin 1 had no effect on [3H]thymidine incorporation or changes in cell number. However, when IL-1 was subsequently added together with IL-2, Tac expression and IL-2-mediated inhibition of cell proliferation was induced. This inhibitory effect was not due to a sensitive subpopulation because greater than 90% of the culture was Tac positive. Taken together, these data show that IL-2 can specifically inhibit oligodendrocyte proliferation and acts via Tac-positive receptors.

Animals↗
PubMed1985

The control of glial populations in brain: changes in astrocyte mitogenic and morphogenic factors in response to injury.

Injury to rat brain induces a 3-10-fold increase in the activity of factors capable of stimulating astrocyte DNA synthesis and cell division in vitro. Maximum mitogenic activity was reached 10-15 days post-lesion in both the tissue surrounding the wound and in the gelfoam filling the wound cavity. Factors capable of transforming the astrocyte morphology from polygonal-flat to fibrous-like (morphogens) could also be observed in brain tissue and showed increased activity beginning at 10 days postlesion. On the other hand, morphogenic activity was very low or absent in gelfoam extracts until 15 days postlesion. Both mitogenic and morphogenic factors were nondiffusible and were partly temperature and trypsin sensitive, i.e. they had the properties of protein-like substances, but seemed different from both epidermal and fibroblast growth factors. As judged by their filtration behavior on Amicon membranes, the molecular weight of mitogens and morphogens ranged from lower than 30,000 to greater than 100,000. Inhibitors of both mitogenic and morphogenic activities with molecular weight lower than 30,000 seemed to be also present in the brain extracts. The factors described here can account for the processes of astrocytosis and astrogliosis observed in vivo in response to CNS injury.

Animals↗
PubMed1985

Characterization of cultured rat oligodendrocytes proliferating in a serum-free, chemically defined medium.

A serumless, chemically defined medium has been developed for the culture of oligodendrocytes isolated from primary neonatal rat cerebral cultures. Combined together, insulin, transferrin, and fibroblast growth factor synergistically induced an essentially homogenous population (95-98%) of cells expressing glycerol-3-phosphate dehydrogenase (EC 1.1.1.8) activity to undergo cell division. Proliferating cels were characterized by several criteria: (i) ultrastructural analysis by transmission electron microscopy identified the cell type as an oligodendrocyte; (ii) biochemical assays showed expression of three oligodendrocyte biochemical markers, induction of both glycerol phosphate dehydrogenase and lactate dehydrogenase (EC 1.1.1.27), and presence of 2',3'-cyclic nucleotide 3'-phosphodiesterase (EC 3.1.4.37); and (iii) immunocytochemical staining showed cultures to be 95-98% positive for glycerol phosphate dehydrogenase, 90% for myelin basic protein, 60-70% for galactocerebroside, and 70% for A2B5. Few cells (less than 5%) stained positive for glial fibrillary acidic protein, and none were detected positive for fibronectin.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1985

Effect of mitogens in various organs and cell culture conditioned media on rat oligodendrocytes.

Extracts prepared from embryonic, neonatal and adult rat brain were examined for the presence of oligodendroglial mitogens. Brain-derived mitogenic activities were found in all developmental stages with specific activity increasing during neonatal development. Extracts from postnatal day 7 contained the highest specific activity. Upon fractionation by molecular weight, each developmental stage expressed a peak of mitogenic activity corresponding to 67,000 daltons. This fraction was able to induce proliferation in cultures grown in serum, serumless chemically defined medium or serum-free medium alone. Neonatal and adult brain extracts had an additional peak of activity at 14,000 daltons. This latter activity was expressed only under serum-supplemented culture conditions. Mitogenic activity was also found in conditioned media from the clonal glioma cell line C6 and primary astrocytes and in extracts derived from neonatal rat liver. These data indicate that a limited range of brain-derived mitogens for oligodendrocytes exist during development and adulthood.

Animals↗
PubMed1982

Glutathione S-transferases of the bovine retina. Evidence that glutathione peroxidase activity is the result of glutathione S-transferase.

We have purified two isoenzymes of glutathione S-transferase from bovine retina to apparent homogeneity through a combination of gel-filtration chromatography, affinity chromatography and isoelectric focusing. The more anionic (pI = 6.34) and less anionic (pI = 6.87) isoenzymes were comparable with respect to kinetic and structural parameters. The Km for both substrates, reduced glutathione and 1-chloro-2,4-dinitrobenzene, bilirubin inhibition of glutathione conjugation to 1-chloro-2,4-dinitrobenzene, 1-chloro-2,4-dinitrobenzene inactivation of enzyme activity and molecular weight were similar. However, pH optimum and energy of activation were found to differ considerably. Retina was found to have no selenium-dependent glutathione peroxidase activity. The total glutathione peroxidase activity fractionated with the transferases in the gel-filtration range of mol.wt. 49000 and expressed activity with only organic hydroperoxides as substrate. Only the more anionic isoenzyme expressed both transferase and peroxidase activity.

Animals↗
PubMed1982

Participation of active oxygen species in 6-hydroxydopamine toxicity to a human neuroblastoma cell line.

Catalase, superoxide dismutase, and dimethylsulfoxide were tested for their ability to prevent the cytotoxic effect of 6-hydroxydopamine (6-OHDA) on the human neuroblastoma line SY5Y. Viability was measured at two time points after 6-OHDA treatment: at 3 hr by means of amino acid incorporation and at 24 hr by trypan blue dye exclusion. Survival of cells treated concomitantly with catalase (50 microgram/ml) and 6-OHDA was at least 90 per cent that of untreated controls. Cells receiving 6-OHDA alone showed less than 30 per cent survival relative to untreated controls. Superoxide dismutase (50 microgram/ml) temporarily protected cells from a high concentration of 60-OHDA. Dimethylsulfoxide treatment increased survival from the control level 24 hr after treatment with 6-OHDA. Two other cell lines (A1B1 human glial cells and CHO fibroblasts) had intermediate and high resistance to the drug, respectively, compared to the low resistance of SY5Y cells. CHO and SY5Y cells had similar responses to 6-OHDA and to H2O2 when tested at twice the molarity of 6-OHDA. Specific activities of three enzymes known to detoxify H2O2 or H2O2-generated organic hydroperoxides (catalase, glutathione S-transferase, and glutathione peroxidase) were compared in the three cell lines. Catalase activity was 2.5 times as high as in A1B1 and CHO cells as in SY5Y cells when expressed as units/mg protein and 7 times as high in units/culture dish. Other enzyme activities showed no correlation to 6-OHDA resistance.

Catalase↗