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J Sanchez-Ramos

Publications and source records attributed to J Sanchez-Ramos.

51 records · Page 3Linked to original sources
PubMed1990

Toxicity of 1-methyl-4-phenylpyridinium for rat dopaminergic neurons in culture: selectivity and irreversibility.

Cultures of dissociated embryonic rat mesencephalic cells were exposed to 10 microM 1-methyl-4-phenylpyridinium (MPP+), a concentration shown earlier to result in loss of greater than 85% of tyrosine hydroxylase (TH)-positive neurons without affecting the total number of cells observed by phase-contrast microscopy. To characterize better the selectivity of the toxic action of MPP+, other parameters were measured reflecting survival and function of dopaminergic or nondopaminergic neurons. Exposure of cultures to 10 microM MPP+ for 48 h reduced TH activity to 11% of control values without reducing protein levels. [3H]Dopamine uptake was reduced to less than 4% of control values, whereas the uptake of gamma-[3H]aminobutyric acid ([3H]GABA) was not affected in these cultures. This same treatment failed to reduce the number of cholinergic cells visualized in septal cultures and did not affect either choline acetyltransferase activity or high-affinity choline uptake. To assess for possible recovery of dopaminergic neurons, cultures were exposed to 10, 1.0, or 0.1 microM MPP+ for 48 h and then kept for up to 6 days in MPP(+)-free medium. After exposure to 10 microM MPP+, the number of TH-positive neurons, their neurite density, TH activity, and [3H]dopamine uptake remained at constant, reduced levels throughout the period of observation after termination of exposure, whereas GABA uptake remained normal. Treatment with lower concentrations of MPP+, i.e., 1.0 and 0.1 microM, induced less pronounced dopaminergic toxic effects. However, no recovery was seen after posttreatment incubation in toxin-free medium. These findings provide evidence that MPP+ treatment results in highly selective and irreversible toxicity for cultured dopaminergic neurons.

1-Methyl-4-phenylpyridinium↗
PubMed1990

Levodopa-responsive parkinsonism in a patient with Down's syndrome.

We report a patient with Down's syndrome (DS) who developed progressive parkinsonian symptomatology at the age of 43 years. His parkinsonism was responsive to levodopa/carbidopa, but he developed end of dose wearing off. We discuss basal ganglia and dopamine abnormalities in DS and suggest that DS may be associated with parkinsonism.

Activities of Daily Living↗
PubMed1989

A case of post-traumatic tic disorder.

We present the case of a 27-year-old man who developed multiple motor tics following closed head trauma with loss of consciousness. Age of onset, lack of family history of tics, and atypical progression of tic severity and location make it unlikely that the patient had Gilles de la Tourette syndrome. Previous reports of post-traumatic tic syndrome are discussed.

Adult↗
PubMed1989

The role of mitochondrial DNA in Huntington's disease.

Huntington's disease is generally considered to be a late-onset neurodegenerative disorder, which follows a protracted course of deteriorating motor control and cognitive impairment. However, in a minority of cases, the onset of symptoms occurs early in life. A preponderance of the juvenile-onset HD victims have inherited the genetic defect from their fathers. This variation in age of onset, based on the sex of the affected parent, has suggested that maternally inherited genes may influence expression of the disorder. We describe a portion of a large Venezuelan HD pedigree in which both the mother and father of three juvenile-onset HD patients share a common maternal lineage. Scanning of mtDNA from members of this family with 43 restriction endonucleases failed to reveal any differences in the mitochondrial genotype that could account for the difference in age of onset between the affected father and his progeny. Members of a related family with an affected father but no juvenile-onset progeny also appeared to share the same mitochondrial genotype. In addition, the mitochondrial gene products from lymphoblast cell lines of these family members were analyzed on polyacrylamide gels after incubation of cells with [35S]methionine, but no detectable alterations were seen. Taken together, these data suggest that the maternally inherited mitochondrial genome does not play a crucial role in determining in age of onset in HD.

Adolescent↗
PubMed1989

Toxic effects of potential environmental neurotoxins related to 1-methyl-4-phenylpyridinium on cultured rat dopaminergic neurons.

Dopaminergic rat mesencephalic neurons in culture were exposed to a group of potential environmental neurotoxins. These cultures, which contained 0.5 to 1% dopaminergic neurons, were a suitable tool for determining nonselective and selective dopaminergic cytotoxicity. Selective toxicity was quantitated as the concentration which destroyed half of the population of dopaminergic neurons as visualized by tyrosine hydroxylase immunocytochemistry. Nonselective toxicity was defined as the concentration of test drug which destroyed half of the entire population of cultured cells as visualized by phase contrast microscopy. The compounds tested were selected to fulfill two molecular criteria underlying the toxic activity of 1-methyl-4-phenylpyridinium (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toward dopaminergic cells: 1) to be a substrate for the selective uptake system of the dopaminergic neurons and 2) to possess a delocalized positive charge related to their ability to inhibit mitochondrial electron transport. Of a total number of 29 compounds tested, MPP+ and its close derivatives, 2'-methyl-MPP+ and p-amino-MPP+, exhibited highly selective dopaminergic toxicity, hence the requirements for a selective dopaminergic neurotoxin are rather strict.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Trauma as an etiology of parkinsonism: a historical review of the concept.

The relationship between trauma and the development of Parkinson's disease has been an issue in neurology since James Parkinson's initial 1817 essay. This paper will delineate the historical development of the concept of trauma as an etiologic agent in Parkinson's disease and parkinsonism. The strong influence of socioeconomic societal forces in the 1870s with regard to liability laws and the subsequent acceptance in the medical community of the role of peripheral trauma in producing Parkinson's disease is presented. We will also review present-day criteria for assigning head trauma an etiologic role in parkinsonism. The discussion will stress current knowledge regarding trauma and parkinsonism, and it will also review the issues of the possible role of the current litigious society's influence on determining a role for trauma in Parkinson's disease.

Brain Injuries↗
PubMed1988

Delayed-onset dystonia associated with corticospinal tract dysfunction.

We report a young man with delayed-onset dystonia secondary to a cerebral infarction. The infarction was caused by an embolic event at the age of 18 months. Delay to onset of dystonia was 16 years and, prior to the onset of dystonia, the patient had profound corticospinal tract dysfunction manifested by a severe hemiparesis. Computed tomography scan revealed infarction of the lentiform nucleus and precentral gyrus. The profound involvement of the corticospinal tract both clinically and radiologically are features not previously described in symptomatic dystonia and contradict the concept that sparing of the corticospinal tract is an essential feature for the onset of acquired dystonia.

Adult↗
PubMed1987

A double-blind evaluation of ciladopa in Parkinson's disease.

We evaluated 32 patients with Parkinson's disease in a double-blind, parallel group, placebo-controlled study with ciladopa (a troponylpiperazine derivative). The dosages administered were 5 mg b.i.d. and 15 mg b.i.d. Significant improvement was found in the gait scores and in the total disability scores in the high dose group (p less than 0.05). In addition, there was a trend toward improvement, though not significant, in the bradykinesia and rigidity scores in the high dose group and in the disability scores in the low dose group. Four patients in the low dose group and five patients in the high dose group decreased their Sinemet doses while no patients increased their Sinemet dose. There were no adverse effects observed in this study. These findings suggest that ciladopa may be an efficacious agent in Parkinson's disease. The low incidence of adverse effects with this agent suggests that higher doses may be utilized and may prove to be more effective.

Aged↗
PubMed1986

1-Methyl-4-phenylpyridinium (MPP+) but not 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) selectively destroys dopaminergic neurons in cultures of dissociated rat mesencephalic neurons.

Dopaminergic neurons were studied in cultures of dissociated cells from the ventral mesencephalon of fetal rat embryos (gestational day E15-16). After a week of growth, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP+) was added to the growth medium for 24 h. Dopaminergic neurons were then visualized with tyrosine hydroxylase (TH) immunocytochemistry or catecholamine (CA) cytofluorescence. Concentrations of MPTP in the range of 10 to 100 microM obliterated CA fluorescence without affecting the number of TH-positive neurons. At concentrations greater than 100 microM, MPTP decreased the number of TH-positive neurons as well as the number of all other cell types. MPP+ (0.1-10.0 microM) produced a decrease in the number of TH-positive neurons without decreasing the total number of all cell types. The findings indicate that MPP+ but not MPTP is able to selectively destroy rat dopaminergic neurons in our cultures. The selective toxicity of MPP+ for dopaminergic neurons was partially prevented by pretreatment and co-incubation with mazindol (a selective inhibitor of dopamine uptake) but not by desipramine or deprenil, in confirmation of the notion that MPP+ enters dopaminergic neurons by the specific uptake mechanism for dopamine.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1978

An artifact of liquid emulsion autoradiography.

The localization of 3H-opiates in the myenteric plexus of the guinea pig ileum is subject to systematic artifact when stretch preparations of the myenteric plexus are dipped into liquid Kodak NTB-3 emulsion for autoradiography. The cause of the artifact was determined to be a discontinuous distribution, or retraction, of emulsion over plexuses. The apposition of frozen freeze-dried ileal sections to dried photographic emulsion avoids this source of error.

Animals↗
PubMedDate not supplied

Attenuation of age-dependent oxidative damage to DNA and protein in brainstem of Tg Cu/Zn SOD mice.

Age-dependent accumulation of oxidative DNA and protein damage in brainstem and striatum was assessed in normal and transgenic (tg) mice which overexpress human Cu/Zn superoxide dismutase (h-SOD1). A marker of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (oxo8dG), was measured at 3, 12, and 18 months of age in control and tg mice. Cu/Zn SOD, but not MnSOD, activities in brainstems and striata from tg mice were increased compared to controls at all ages. At 18 months, oxo8dG levels were increased by 58% in brainstem and by 21% in striatum of control mice. In the tg mice, brainstem and striatal oxo8dG levels were increased to a lesser extent than in the corresponding controls. Protein oxidation (carbonyl content), was increased by 59% at 18 months in control brainstem, but not in striatum, and the increase was significantly attenuated in the tg mice. In summary, oxidative damage to DNA and protein increased with age in brainstem (and to a lesser extent in striatum), and augmented Cu/Zn SOD activity modified the extent of DNA and protein damage.

8-Hydroxy-2'-Deoxyguanosine↗
PubMedDate not supplied

The X-gal caution in neural transplantation studies.

Cell transplantation into host brain requires a reliable cell marker to trace lineage and location of grafted cells in host tissue. The lacZ gene encodes the bacterial (E. coli) enzyme beta-galactosidase (beta-gal) and is commonly visualized as a blue intracellular precipitate following its incubation with a substrate, "X gal," in an oxidation reaction. LacZ is the "reporter gene" most commonly employed to follow gene expression in neural tissue or to track the fate of transplanted exogenous cells. If the reaction is not performed carefully-with adequate optimization and individualization of various parameters (e.g.. pH, concentration of reagents, addition of chelators, composition of fixatives) and the establishment of various controls--then misleading nonspecific background X-gal positivity can result, leading to the misidentification of cells. Some of this background results from endogenous nonbacterial beta-gal activity in discrete populations of neurons in the mammalian brain; some results from an excessive oxidation reaction. Surprisingly, few articles have empha sized how to recognize and to eliminate these potential confounding artifacts in order to maximize the utility and credibility of this histochemical technique as a cell marker. We briefly review the phenomenon in general, discuss a specific case that illustrates how an insufficiently scrutinized X-gal positivity can be a pitfall in cell transplantation studies, and then provide recommendations for optimizing the specificity and reliability of this histochemical reaction for discerning E. coli beta-gal activity.

Animals↗