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Biomedical subjects

W J Weiner

Publications and source records attributed to W J Weiner.

At least 19 recordsLinked to original sources
PubMed1992

21-aminosteroids interact with the dopamine transporter to protect against 1-methyl-4-phenylpyridinium-induced neurotoxicity.

U-78518F, a 21-aminosteroid from the novel family of lipid peroxidation inhibitors (lazaroids), increased survival of dopamine (DA) neurons in mesencephalic cell cultures incubated with the neurotoxin 1-methyl-4-phenylpyridinium (MPP+). Protection against DA neuron death occurred with increasing concentrations of U-78518F up to 30 microM. Non-specific toxicity produced with higher concentrations of MPP+ was not affected by the lazaroid. U-78518F inhibited cellular uptake of [3H]MPP+ and [3H]DA, but not that of gamma-[3H]aminobutyric acid. In human striatal membrane preparations, U-78518F competed with [3H]mazindol for binding to the DA transporter, with a calculated Ki value of 10 microM. Two of four lazaroids tested inhibited [3H]DA uptake in the cell culture system. The protective effects of 21-aminosteroids in MPP(+)-induced neurotoxicity are, in part, a function of the interaction of these agents with the DA transporter.

1-Methyl-4-phenylpyridinium↗
PubMed1992

Autonomic dysfunction in men with Parkinson's disease.

Forty-eight men with Parkinson's disease (PD) were interviewed utilizing a questionnaire which evaluated autonomic function. The study population included PD patients (mean age: 65.8 years, mean duration of PD: 8 years) and 32 elderly healthy nonparkinsonian males (mean age: 70.4 years). We found a significantly higher prevalence of the following symptoms of autonomic dysfunction in the parkinsonian patients: erectile dysfunction (60.4 vs. 37.5%), sensation of incomplete bladder emptying (41.6 vs. 15.6%), urgency (45.8 vs. 3.125%), constipation (43.9 vs. 6.25%), dysphagia (22.9 vs. 6.25%) and orthostatic dizziness (21.95 vs. 0%). Eighty-nine percent of parkinsonian patients had at least one of these autonomic symptoms, compared to 43% of control subjects (p less than 0.05). This study is the first comprehensive survey of autonomic symptomatology in PD compared to elderly healthy controls and confirms that autonomic nervous system dysfunction is a pervasive problem in PD. Erectile dysfunction is a significant problem in this patient group and contributes to deterioration in the quality of life.

Aged↗
PubMed1991

Prior history of head trauma in Parkinson's disease.

The purpose of this study was to evaluate the relationship between head trauma and Parkinson's disease (PD). A questionnaire was completed by 97 PD patients (mean age 68.6 years, duration of disease 6.4 years) and 64 spouses acting as controls (mean age 63 years). Thirty-one PD patients reported head trauma before onset of PD (mean 32.3 years earlier), whereas 11 controls reported head injury before completing the survey (mean 26 years earlier) (p less than 0.05). Twenty PD patients and five controls reported head injury associated with alteration or loss of consciousness (p less than 0.05). Injury occurred a mean of 37.7 years before onset of PD and 37.2 years before survey completion in the two groups, respectively. In both of these comparisons we adjusted the frequencies to eliminate sex differences between groups. Comparison of new frequencies showed differences that were not significant. However, a trend toward significance was observed when examining head trauma with alteration of consciousness. Other investigators have reported similar results indicating that previous head trauma may be a risk factor in the etiology of PD. However, recall bias might have an effect on the outcome of these studies and this is discussed. The relationship between head trauma and PD is still tenuous.

Adult↗
PubMed1991

Distribution and number of transferrin receptors in Parkinson's disease and in MPTP-treated mice.

Transferrin is a glycoprotein that functions primarily to deliver iron to the cell. Recent studies suggest that the transferrin receptor mediates the intracellular delivery and transport of iron bound to transferrin in the CNS. Iron-catalyzed free radical generation has been proposed as a possible cause of nigral cell death in Parkinson's disease. Our hypothesis is that abnormal iron handling by the transferrin receptor may contribute to the formation of free radical species which catalyze the lipid peroxidation of nigral cell membranes. We have assessed the number of transferrin receptors on membrane fractions prepared from the human striatum from control subjects and patients with Parkinson's disease. Equilibrium-binding studies demonstrated a reversible, saturable, and high-affinity transferrin binding site (KD = 3 nM) in human brain membranes. Regional binding assays indicate that the number of transferrin receptors in the putamen was reduced significantly in Parkinson's disease. The density of transferrin receptors was unaltered in membranes prepared from the caudate nuclei and the globus pallidus. To address the possibility that transferrin receptors are located on dopaminergic terminals, we have examined the distribution and number of transferrin receptors in the striatum of MPTP-treated mice using in vitro autoradiographic methods. In these experiments, the loss of dopaminergic terminals in the striatum was visualized by differential [3H]mazindol uptake site autoradiography. A marked reduction in the density of both transferrin receptors and [3H]mazindol binding sites was observed in the mouse striatum 7 days post-MPTP treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1991

A retrospective analysis of the effects of anticholinergic medication on memory performance in Parkinson's disease.

We examined the effects of anticholinergic medication on memory function in 113 patients with idiopathic Parkinson's disease (PD). Subjects were divided into three disease duration groups: early, middle, and advanced. The battery consisted of three tasks assessing memory of logical discourse, semantically related words, and figural material. We found no evidence of anticholinergic-induced memory dysfunction in any of the three groups. Analysis of covariance indicated that age was not a significant variable; however, dementia may have influenced the relationship between anticholinergic medication and memory scores. Our results indicate that anticholinergic medication does not uniformly compromise memory function in PD patients.

Aged↗
PubMed1991

Visuospatial impairment in Parkinson's disease.

We explored the nature of the visuospatial deficit in Parkinson's disease (PD) and its progression as a function of disease duration. We compared the performance of 183 patients with idiopathic PD and 90 control subjects matched for age and education on six visuospatial measures. We divided patients into three groups according to the disease duration: early (1 to 4 years), middle (5 to 10 years), and advanced (greater than 10 years). Performance deteriorated in five of the six visuospatial measures, as a function of disease duration. However, the pattern of visuospatial decline depended on whether dementia was present. The results were not influenced by age or anticholinergic medication. These findings support the presence of visuospatial deficits in PD patients, with a changing pattern of impairment related to dementia and progression of the disease.

Aging↗
PubMed1990

Sleep disorders and sleep effect in Parkinson's disease.

It has been suggested that sleep may have a positive effect on morning motor symptoms in Parkinson's disease (PD). We examined this possibility and also looked at common sleep disorders in PD. Seventy-eight PD patients and 43 normal elderly subjects answered a questionnaire. Of the PD patients, 43.6% reported improved motor symptoms in the morning, 37.2% worse, and 19.2% unchanged compared to the rest of the day. No difference was found between morning-better and -worse groups with respect to age, duration or stage of PD; antiparkinsonian medications utilized, and predominant motor symptoms. However, the morning-same group had a shorter duration of PD and less severe disease and required fewer dopaminergic medications. Sleep disorders were seen with equal frequency in the morning-better and -worse groups. Our results suggest that sleep does not have a direct effect on morning motor function. Alterations in morning motor symptomatology probably represent a manifestation of motor fluctuations. Sleep fragmentation and spontaneous daytime dozing occurred much more frequently in PD patients than controls. In addition, nocturnal vocalizations and daytime hallucinations occurred only in the PD group.

Aged↗
PubMed1990

Characterization and distribution of transferrin receptors in the rat brain.

Transferrin receptors were characterized with 125I-ferrotransferrin on membrane fractions prepared from the rodent forebrain. The distribution of transferrin receptors in the rat brain was investigated further by in vitro autoradiography. Saturation binding analysis revealed an apparent single class of sites with a dissociation constant of 2 nM and a binding site density of 15 pmol/g. The Hill coefficient derived from these data was 1.05, indicating the absence of cooperativity and that 125I-ferrotransferrin binds to a single class of sites. Estimates of the kinetically determined KD for forebrain membranes were within the 2-4 nM range, in agreement with the equilibrium measurements. Apotransferrin and ferrotransferrin competitively displaced the binding of 125I-ferrotransferrin, while ferritin, albumin, and cytochrome c failed to compete for the binding site. Ceruloplasmin, the copper transport protein, was a weak inhibitor of 125I-ferrotransferrin binding. Autoradiographic localization studies demonstrate a heterogeneous distribution of transferrin receptors in the rat brain. Transferrin receptor densities were markedly elevated over the cerebral cortex and the hippocampus. Moderate to high 125I-ferrotransferrin binding was also apparent throughout areas involved in motor functions, including the caudate-putamen, the nucleus accumbens, the substantia nigra, the red nucleus, and the cerebellum.

Animals↗
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

Acetaminophen metabolism by cytochrome P450 monooxygenases in Parkinson's disease.

It has been suggested that alterations in the activity of cytochrome P450 monooxygenases may play a role in the pathogenesis of Parkinson's disease, particularly in patients who had onset before the age of 40. We studied the P450-mediated metabolism of acetaminophen to 3-hydroxy-acetaminophen in 26 patients with Parkinson's disease and in 18 control subjects. After subjects ingested 1,000 mg acetaminophen, urine was collected under controlled conditions. Acetaminophen and 3-hydroxy-acetaminophen were measured in the urine using newly developed high-pressure liquid chromatography methods. The ratio of 3-hydroxy-acetaminophen to acetaminophen was calculated for each patient and no significant differences were observed in patients compared with control subjects. Abnormal metabolism was not observed in patients who had onset of Parkinson's disease at or before the age of 40. In addition, no difference in metabolic activity was observed between the patients who were treated with levodopa/carbidopa and those who were not treated. These findings suggest that there are no alterations of P450-mediated metabolism of acetaminophen in patients with Parkinson's disease.

Acetaminophen↗
PubMed1989

Hemichorea-hemiballismus associated with acquired immune deficiency syndrome and cerebral toxoplasmosis.

A young woman had hemichorea-hemiballismus subsequently found to be secondary to a cerebral toxoplasmosis infection complicating human immunodeficiency virus infection. This patient had the sixth reported case of acquired immune deficiency syndrome (AIDS) with hemichorea-hemiballismus, and each has been secondary to cerebral toxoplasmosis. The presence of hemichorea-hemiballismus in a young patient should suggest a diagnosis of AIDS and in particular the diagnosis of secondary cerebral toxoplasmosis. Other movement disorders that occur in AIDS are discussed.

Acquired Immunodeficiency Syndrome↗
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↗