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Biomedical subjects

P D Swanson

Publications and source records attributed to P D Swanson.

At least 19 recordsLinked to original sources
PubMed2001

A laminated, flex structure for electronic transport and hybridization of DNA.

We have developed the first prototypes of a three-dimensional, electrophoretically driven microlaboratory for the analysis of proteins and DNA. By selecting the appropriate spacing and geometrical configuration, oligonucleotides were transported, in a controlled, rapid fashion, by electrophoresis in free-space. Transport efficiencies over 2 mm distances exceeded 70%. Electrodes of similar design were combined with an electronically addressed DNA hybridization chip to form a fully electrophoretic microlaboratory. In this instance, gold-plated copper electrodes were patterned on a 2 mil thick polyimide substrate. This polyimide layer was stiffened with 20 mil of polyimide to provide support for flip-chip bonding of our standard 100-site Nanochip. This composite structure illustrated three-dimensional transport of target oligonucleotides, through a via in the polyimide, along a series of electrodes and onto the diagnostic chip. Upon reaching the diagnostic chip, electronic hybridization was performed for a competitive reverse dot blot assay. The electronic assay showed a specific to nonspecific ratio in excess of 20:1. These results suggested that this type of structure might be of practical consequence with the development of a microlaboratory for biowarfare applications.

Base Sequence↗
PubMed2000

The EcoRV genetic polymorphism of human monoamine oxidase type A is not associated with Parkinson's disease and does not modify the effect of smoking on Parkinson's disease.

We previously observed an association with Parkinson's (PD), and modification of the effect of smoking on PD, by a polymorphism of the monoamine oxidase B (MAO-B) gene. The A form of monoamine oxidase (MAO-A) shares with MAO-B many characteristics that could be relevant to PD, especially proneuroxicant bioactivation and dopamine metabolism. MAO-A is also inhibited by tobacco smoke, which bears an apparent protective effect on PD. We investigated the possibility that MAO-A genetic variants may also be involved in predisposition to PD and in modification of the effect of smoking. Three-hundred and seventy-one subjects--145 idiopathic PD cases and 226 age/gender-matched controls--were genotyped for the EcoRV polymorphism of MAO-A gene which has been related to increased enzyme activity. MAO-A EcoRV polymorphism was neither significantly associated with PD nor did it modify the inverse relationship with smoking. These results suggest that the EcoRV polymorphism of MAO-A is not an important biomarker of PD risk.

Adult↗
PubMed2000

Genetic polymorphism of dopamine D2 receptors in Parkinson's disease and interactions with cigarette smoking and MAO-B intron 13 polymorphism.

Genetic polymorphisms of dopamine D2 receptors (DRD2) may be susceptibility factors for Parkinson's disease due to their influence on dopamine response and association with cigarette smoking, which is inversely related to risk of Parkinson's disease. Relations of TaqIA and TaqIB DRD2 genotypes with Parkinson's disease were investigated and tested for interactive effects with smoking and the monoamine oxidase B (MAO-B) intron 13 polymorphism previously found to be related to smoking. Study subjects were 152 cases of idiopathic Parkinson's disease and 231 controls. The smoking history of all genotyped subjects was known. Subjects of genotype B12 were more frequent among cases than controls (27% and 23.8%, respectively), and were more frequent among "ever smokers" than "never smokers", among controls (27.8% and 17.2%, respectively), although these associations were not statistically significant. Neither TaqIA or TaqIB genotypes modified the inverse relation of smoking and Parkinson's disease. When genotypes for DRD2 were considered in combination with genotypes for intron 13 of MAO-B, genotype combinations with high risk of Parkinson's disease were found; although the MAO-B/DRD2 interaction did not reach statistical significance after Bonferroni correction for multiple comparisons, these results are suggestive of a possible synergism between MAOB and DRD2 genes with respect to Parkinson's disease.

Adult↗
PubMed2000

Mitochondrial ND1 sequence analysis and association of the T4216C mutation with Parkinson's disease.

Mitochondrial dysfunction originating from mutations in Complex I genes may play a role in the pathogenesis of Parkinson's disease (PD). In this study, the entire ND1 coding sequence was sequenced in 84 newly diagnosed PD cases and 127 age/gender-matched controls. Numerous missense mutations were found at low frequency (<5%), whereas a thymidine to cytosine missense mutation at position 4216 that results in the replacement of tyrosine with histidine was found in 25% of the PD case samples and in 18% of the controls. When calculated according to gender, the 4216 mutation was observed in 26% of the male cases versus 16% of male controls (Odds Ratio [OR] = 1.85; 95% CI = 0.79-4.34). In contrast, females exhibited approximately equal frequencies among cases (22.5%) and controls (21%), yielding an OR of 1.08 (95% C.I. = 0.36-3.22). The findings indicate only a weak association of this genetic variant with PD.

Humans↗
PubMed1999

Dietary factors in Parkinson's disease: the role of food groups and specific foods.

PURPOSE: The association between self-reported past food intake and Parkinson's disease (PD) was investigated in a case-control study of men and women aged 40-89 years. METHODS: Newly diagnosed idiopathic PD cases were ascertained from neurologists, and from outpatient and pharmacy computerized databases, at the Group Health Cooperative (GHC) clinics in the Puget Sound region of Washington state. Control subjects were chosen from the GHC patient roster and had no reported history of diagnosed neurodegenerative disease. Dietary data were obtained from structured questionnaires. RESULTS: An increase in PD risk with increasing intake was noted for foods that contain animal fat and foods containing vitamin D. Intake of fruits, vegetables, meats, bread and cereals, or foods containing vitamins A, C, E, or iron was not significantly related to PD risk. Vitamin use, in general, was also not found to be related to PD risk, although a significant trend of increasing risk of PD was noted for intake of vitamin A supplements. CONCLUSIONS: Although these data support previous findings of no association of past intake with most food groups and PD risk, they confirm an increased risk of PD associated with foods containing animal fat.

Adult↗
PubMed1998

A genetic polymorphism of MAO-B modifies the association of cigarette smoking and Parkinson's disease.

In a population-based case-control study, we found a reversal of the association of cigarette smoking with Parkinson's disease (PD) in relation to the monoamine oxidase B intron 13 genetic polymorphism. A reduced PD risk related to pack-years of smoking was detected for persons with the G allele, whereas an opposite effect was found among persons with the A allele. These results indicate an unexplained interaction between cigarette smoking and this genetic polymorphism.

Adult↗
PubMed1997

Association of a polymorphism in intron 13 of the monoamine oxidase B gene with Parkinson disease.

Monoamine oxidase B (MAO-B) is an enzyme that has relevance for Parkinson disease (PD) because of its roles in catabolizing dopamine and potentially activating exogenous neurotoxicants. A polymorphism of the gene encoding MAO-B has been identified as a single base change (A or G) in intron 13 of the X chromosome. The A allele was previously associated with an approximately twofold risk of PD. The present study compared A and G allele frequencies between newly diagnosed idiopathic PD cases and a control group free of neurodegenerative diseases. All study subjects were Caucasian. Cases were 37 men and 25 women, age 37-80 years; controls were 50 men and 29 women, age 45-82 years. MAO-B genotype was determined by the allele-specific polymerase chain reaction on DNA extracted from peripheral lymphocytes. In complete contrast to previous studies, elevated risks were detected with the G allele. The age-adjusted odds ratio for the G allele in males was 1.87 ((95% confidence interval) 0.78-4.47). Among females the age-adjusted odds ratios were 5.00 ((95% confidence interval) 1.13-22.1) for the GA genotype and 5.60 ((95% confidence interval) 1.01-30.9) for the GG genotype. These findings, although of limited statistical precision, suggest that the G allele of this MAO-B polymorphism may relate to PD risk.

Adult↗
PubMed1996

Selegiline and lymphocyte superoxide dismutase activities in Parkinson's disease.

Superoxide dismutases (SODs) are metalloenzymes that detoxify superoxide radicals, and occur in cytosolic (Cu,Zn-SOD) and mitochondrial (Mn-SOD) forms in multiple tissues, including brain. A neuroprotective effect against oxide stressor exposures may be provided by SOD, although excessive enzyme activity can produce cell injury by formation of hydroxyl radical from hydrogen peroxide. We measured Cu,Zn-SOD and Mn-SOD activities in peripheral lymphocytes of 43 newly diagnosed idiopathic Parkinson's disease (PD) cases and 62 age- and sex-matched controls free of neurodegenerative disorders. Significant excesses of both SOD forms were found among PD cases compared with controls; however, the excesses were found exclusively among PD patients treated with the monoamine oxidase inhibitor selegiline (L-deprenyl). Enzyme-linked immunosorbent assays (ELISAs) confirmed that the activity excesses were due to increased protein rather than more highly reactive enzymes in lymphocytes of PD cases. Our findings clearly indicate the importance of selegiline on measured Cu,Zn-SOD and Mn-SOD activity in peripheral lymphocytes. Characterizing a possible therapeutic value of SOD will require longitudinal assessments of SOD in relation to PD progression.

Antiparkinson Agents↗
PubMed1995

Diagnosis of inherited metabolic disorders affecting the nervous system.

Knowledge of the molecular causes for genetic diseases that affect the nervous system is rapidly expanding. Especially striking has been the finding in several autosomal dominant neurodegenerative disorders that unstable expansions of trinucleotide repeats are responsible for the genetic disorder and that the length of the repeat can be correlated with the age of onset and the severity of symptoms. Phenotypic heterogeneity in many disorders associated with enzyme deficiencies can often be linked to the amount of residual enzyme activity occurring with different gene mutations. Making a specific diagnosis of a neurological disorder associated with genetically determined metabolic defects requires access to a laboratory that can assist in arranging for appropriate testing to be carried out. In some disorders such as the aminoacidurias diagnostic metabolic studies can be performed in hospital clinical chemistry laboratories. In others, such as the lysosomal storage diseases, a laboratory that carries out special lipid analyses and white blood cell enzyme assays will be necessary. DNA mutational analyses are becoming commercially available for diagnosing many disorders such as mitochondrial diseases and those conditions associated with expanded trinucleotide repeats. It may be necessary to contact individual research laboratories when confronted with a disorder that has been newly discovered or that is very rare. A computerised directory of specialised laboratories that perform disease specific testing for genetic disorders should be useful in choosing the appropriate diagnostic or research laboratory.

Humans↗
PubMed1993

DNA deletion associated with hereditary neuropathy with liability to pressure palsies.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that causes episodes of focal demyelinating neuropathy following minor trauma to peripheral nerves. We assign the HNPP locus to chromosome 17p11.2 and demonstrate the presence of a large interstitial deletion associated with this disorder in three unrelated pedigrees. De novo deletion is documented in one pedigree. The deleted region appears uniform in all pedigrees and includes the gene for peripheral myelin protein 22 (PMP-22), suggesting that underexpression of PMP-22 may cause HNPP. The deletion in HNPP spans approximately 1.5 Mb and includes all markers that are known to map within the Charcot-Marie-Tooth neuropathy type 1A (CMT1A) duplication. Furthermore, the breakpoints in HNPP and CMT1A map to the same intervals in 17p11.2, suggesting that these genetic disorders may be the result of reciprocal products of unequal crossover.

Chromosome Mapping↗
PubMed1992

Peripheral blood cell activities of monoamine oxidase B and superoxide dismutase in Parkinson's disease.

Monoamine oxidase type B (MAO-B) and superoxide dismutase (SOD) are two enzyme systems that are potentially relevant to an oxidative stress model of Parkinson's disease (PD) causation. Activities of MAO-B in platelets (nmol/10(8) cells/hr) and total SOD in lymphocytes (U/mg protein) were assayed among 28 cases of idiopathic PD and 22 controls. As anticipated, MAO-B was lowest in PD cases on selegiline (L-deprenyl) therapy (mean 1.10). There was a slight deficit of MAO-B among male cases not taking selegiline compared to controls (3.78 vs. 4.15), but the opposite trend was observed for females (6.18 vs. 4.16). SOD was slightly higher in cases (7.40), than controls (6.81). Excess SOD among PD cases was seen irrespective of gender, age, or selegiline treatment, although none of the differences was statistically significant. Future research on SOD should take advantage of the availability of assays specific for the cytosolic and mitochondrial forms of the enzyme.

Adult↗
PubMed1990

Vaccine-associated paralytic poliomyelitis. Regional case series and review.

We present 10 cases of vaccine-associated paralytic poliomyelitis from Washington State to better acquaint physicians with the signs and symptoms of this condition. Diagnosis may be delayed, and milder cases may be overlooked, owing to the unfamiliarity of physicians with the condition. Based on these 10 cases, a rate of 6.4 cases (recipient plus contact) per million live births is estimated for the period 1966 through 1988 in Washington. This rate is higher than calculated for the nation as a whole. The explantation for this difference is unknown, although several possibilities exist, including case clustering.

Adult↗
PubMed1986

Magnetic resonance imaging in cerebrotendinous xanthomatosis.

In a patient with cerebrotendinous xanthomatosis, magnetic resonance imaging (MRI) revealed findings of demyelination in the cerebral white matter, which was also hypodense on CT. The MRI abnormality seemed to be clinically significant in this patient with progressive dementia and abnormal gait.

Atrophy↗
PubMed1985

Inhibition of brain mitochondrial Ca2+ transport by amiloride analogues.

Rat brain mitochondrial Ca2+ uptake and release were examined in the presence of amiloride (3,5-diamino-6-chloro-N-(diaminomethylene)-pyrazinecarboxamide) and nineteen amiloride analogues. Amiloride, an inhibitor of Na+-Ca2+ exchange in plasmalemma membranes, did not affect energy-dependent Ca2+ uptake, whereas several other analogues were inhibitors. Similarly, amiloride did not alter Ca2+ release in the presence or absence of Na+. However, some analogues were found that stimulated and others that inhibited Ca2+ release. While many of these analogues reduced mitochondrial respiratory control ratios, two analogues were identified which inhibited Ca2+ uptake but did not alter mitochondrial respiratory control. Similarly two analogues were identified which inhibited Ca2+ efflux without affecting respiratory control.

Amiloride↗
PubMed1985

Inhibition of synaptosomal membrane Na+-Ca2+ exchange transport by amiloride and amiloride analogues.

Na+-Ca2+ exchange in rat brain synaptosomal plasmalemma vesicles is reversibly inhibited by amiloride (3,5-diamino-6-chloro-N-(diaminomethylene)pyrazinecarboxamide++ +). This drug (pKa = 8.7) inhibits Na+-dependent Ca2+ uptake more effectively at basic pH values than at neutral pH values, indicating that the positively charged form of amiloride is the active moiety. Twenty amiloride analogues were examined for ability to inhibit Na+-Ca2+ exchange. These studies demonstrate that the 6-chloro group, the 5-amino substituent, and the carbonyl guanidinium moiety are essential for drug inhibition of Na+-Ca2+ exchange. N-Benzyl amiloride derivatives such as 3,5-diamino-6-chloro-N-(benzylamino-aminomethylene)pyrazinecarb oxamide (benzamil) and 3,5-diamino-6-chloro-N-(2-phenethylamino-aminomethylene)p yrazinecarboxamide are more potent inhibitors of Na+-dependent Ca2+ uptake than is amiloride. The amiloride analogue pattern of interaction with the Na+-Ca2+ exchange system is distinct from the inhibition patterns of the epithelial Na+ channel and the Na+-H+ exchange transport system.

Adenosine Triphosphate↗