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Biomedical subjects

N Quinn

Publications and source records attributed to N Quinn.

At least 73 records · Page 4Linked to original sources

Differentiation of multiple system atrophy from idiopathic Parkinson's disease using proton magnetic resonance spectroscopy.

Proton magnetic resonance spectroscopy, localized to the lentiform nucleus, was carried out in 7 patients with the pure or predominantly striatonigral variant (SND) of multiple system atrophy (MSA), 5 patients with the olivopontocerebellar variant of MSA, 9 patients with a clinical diagnosis of idiopathic Parkinson's disease (IPD), and 9 healthy age-matched controls. The MSA group with predominantly striatonigral involvement showed a significant reduction in the N-acetylaspartate (NAA)/creatine ratio (median, 1.19; range, 0.96-2.0; p < 0.02) compared with the NAA/creatine ratio from the control group (median, 1.76; range, 1.61-2.0). In contrast, the IPD group had a normal NAA/creatine ratio (median, 1.82; range, 1.19-2.31; p > 0.05). The NAA/creatine ratio was markedly reduced in 6 of the SND patients and in only 1 IPD patient. The choline/creatine ratio was also significantly lower in the SND group (median, 1.02; range, 0.91-1.23; p < 0.04) compared with the control group (median, 1.22; range, 1.05-1.65). The IPD group showed a normal lentiform choline/creatine ratio (median, 1.13; range, 0.89-1.65; p = 0.25) compared with controls. The olivopontocerebellar group also showed a significant reduction in the NAA/creatine ratio from the lentiform nucleus (median, 1.47; range, 1.22-1.68; p < 0.01) compared with the controls as well as a nonsignificant reduction in the choline/creatine ratio (median, 0.93; range, 0.85-1.27; p < 0.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Multiple system atrophy.

The past year has seen advances in delineating the clinical features, natural history and imaging characteristics of multiple system atrophy. The initiating pathogenetic mechanisms remain unknown. However, any aetiological or pathophysiological hypothesis must consider not only neuronal loss and gliosis but also the recently described characteristic oligodendrolial cytoplasmic inclusions.

Brain↗

Olfactory function in atypical parkinsonian syndromes.

INTRODUCTION: Olfaction is markedly impaired in patients with idiopathic Parkinson's disease (IPD). This deficit contrasts with reports of preserved or only mildly reduced olfaction in patients with atypical parkinsonism. However, the sensitivity and specificity of olfactory function testing in the differential diagnosis of parkinsonian syndromes has not been studied. In addition, olfactory function in patients with corticobasal degeneration (CBD) is unknown. MATERIAL AND METHODS: Using the University of Pennsylvania Smell Identification Test (UPSIT) with a test score ranging from 0 to 40 we studied olfactory function in patients with IPD as well as other parkinsonian syndromes including CBD and progressive supranuclear palsy (PSP). RESULTS: UPSIT scores in 118 patients with IPD, 29 with MSA, 15 with PSP, and 7 patients with CBD, as well as in 123 healthy control subjects revealed a marked impairment in the IPD group in contrast to mild impairment in MSA patients and normal olfaction in PSP and CBD patients. An UPSIT score of 25/40 was associated with a sensitivity of 77% and a specificity of 85% in differentiating IPD from atypical parkinsonism. CONCLUSIONS: These results indicate that olfactory function is differentially impaired or preserved in distinct parkinsonian syndromes and that it might also have some value as a diagnostic pointer. Thus, preserved or mildly impaired olfactory function in a parkinsonian patient is more likely to be related to atypical parkinsonism such as MSA, PSP or CBD, whereas markedly reduced olfaction is more suggestive of IPD.

Adult↗

"Minimal change" multiple system atrophy.

We describe the pathological findings in two patients who developed atypical parkinsonism and autonomic failure, leading to a diagnosis of multiple system atrophy (MSA). Postmortem examination of the brain showed cell loss restricted to substantia nigra and locus coeruleus. However, glial cytoplasmic inclusions (GCIs) were present in both cases. We propose that GCIs are highly suggestive of a pathological diagnosis of MSA in the absence of detectable cell loss outside pigmented brain stem nuclei and that brains from cases of atypical parkinsonism should routinely be examined for their presence.

Adult↗

Asymmetrical pre-synaptic and post-synpatic changes in the striatal dopamine projection in dopa naïve parkinsonism. Diagnostic implications of the D2 receptor status.

Nine L-dopa na ve patients with clinically diagnosed parkinsonism were studied using positron emission tomography with 6-L-[18F]fluorodopa ([18F]dopa, a pre-synaptic tracer) and [11C]raclopride (which binds to D2 receptors). Putamen [18F]dopa uptake was reduced in all patients, confirming a loss of function affecting the nigrostriatal projection. In eight patients the putamen with the lowest [18F]dopa uptake (always contralateral to the clinically most affected side) had the highest [11C]raclopride binding, suggesting upregulation of the post-synaptic D2 receptors. In the ninth patient [11C]raclopride binding was lower in the putamen with the lowest [18F]dopa uptake, indicating an additional post-synaptic deficit. All nine patients were shown to be L-dopa responsive. The subsequent clinical course of the former eight patients has been typical of idiopathic Parkinson's disease, whilst the ninth patient has developed postural hypotension, urinary incontinence and respiratory stridor typical of multiple system atrophy. Reduced [11C]raclopride binding in L-dopa naïve parkinsonian patients might serve as a useful early marker of this condition.

Adult↗

Striatal D2 receptor status in patients with Parkinson's disease, striatonigral degeneration, and progressive supranuclear palsy, measured with 11C-raclopride and positron emission tomography.

Equilibrium striatal: cerebellar 11C-raclopride (RAC) uptake ratios reflect the density of striatal dopamine D2 binding sites. Using positron emission tomographic scanning we have measured striatal RAC uptake in 6 untreated patients with Parkinson's disease (PD), 5 chronically treated patients with PD and a fluctuating response to L-dopa, 10 patients with striatonigral degeneration (SND), and 9 patients with progressive supranuclear palsy (PSP). Regional cerebral blood flow was determined also, with C15O2. Mean striatal: cerebellar RAC uptake was not significantly different from normal in untreated patients with PD, though 2 of these 6 patients showed significantly increased putamen tracer binding. Mean caudate and putamen: cerebellar RAC uptake ratios of the group with PD and a fluctuating response to L-dopa were significantly reduced by 30% and 18%, respectively. The patients with SND had lesser, but significant, 10% and 11% decreases in mean caudate and putamen: cerebellar RAC uptake ratios, respectively, whereas patients with PSP showed 24% and 9% reductions in caudate and putamen: cerebellar RAC binding. Striatal and frontal blood flow were significantly reduced in patients with PSP, but not in patients with PD or SND. In conclusion, striatal D2 binding potential is normal or raised in untreated patients with PD, but reduced in patients with PD and a fluctuating response to L-dopa. Patients with SND and PSP show a decrease in striatal RAC binding, but to a lesser extent than patients with PD and a fluctuating response to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Intravenous boluses and continuous infusions of L-dopa methyl ester in fluctuating patients with Parkinson's disease.

In six patients with Parkinson's disease exhibiting severe "on-off" phenomena, a 200-mg intravenous bolus of either L-DOPA or of its methyl ester were equally effective in reversing motor deficits, although the duration of action of the methyl ester was shorter. There were no marked differences in pharmacokinetic parameters for L-DOPA plasma levels after administration of L-DOPA and the methyl ester. In three patients, optimal infusion rates for the maintenance of mobility were established for L-DOPA and L-DOPA methyl ester. Both drugs were able to maintain patients "on" throughout a 12-h infusion period. However, on average the optimal infusion rate of L-DOPA methyl ester was 2.7 times greater than that for L-DOPA. There was no marked difference in the plasma levels of L-DOPA achieved, but 3-O-methyl DOPA levels increased more after infusion of L-DOPA methyl ester than after infusion of L-DOPA itself. The half-life of elimination and volume of distribution of L-DOPA formed from the methyl ester were markedly increased compared with values obtained after either an intravenous bolus of methyl ester or after an intravenous infusion of L-DOPA itself. An intravenous bolus of L-DOPA methyl ester produces an equivalent magnitude of clinical response to the same dose of L-DOPA. However, higher optimal infusion rates of methyl ester than L-DOPA are required to produce continuous effect. The pharmacokinetic handling of L-DOPA methyl ester given by intravenous infusion may differ from that of L-DOPA when given by the same route.

Aged↗

Cerebellar syndrome in myxoedema revisited: a published case with carcinomatosis and multiple system atrophy at necropsy.

One of six patients in a 1960 paper on "Cerebellar syndrome in myxoedema" was subsequently found to have adenocarcinoma. General post-mortem revealed carcinomatosis and basal pneumonia. Neuropathological examination revealed the changes of multiple system atrophy. The relationship between hypothyroidism, carcinoma, and cerebellar, pontine and striatonigral degeneration is discussed.

Adenocarcinoma↗

Essential tremor.

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Data Collection↗

Reaction times and visuospatial processing in Parkinson's disease.

Three motor reaction time tasks which differed in visuospatial complexity but not in motor demands were completed by a group of Parkinson's disease patients and a group of matched control subjects. Response initiation times increased with visuospatial difficulty, whereas movement times remained within a similar range. The two groups differed in response initiation and movement execution times across all reaction time conditions. However, there was no disproportionate increase in response initiation times between an initial nonspatial condition and more complex visuospatial conditions in Parkinson disease patients, and the patients did not make more errors than control subjects. The results do not give support to the hypothesis of a generalised visuospatial deficit in Parkinson's disease.

Affect↗

Overexpression, purification, and characterization of isochorismate synthase (EntC), the first enzyme involved in the biosynthesis of enterobactin from chorismate.

Isochorismate synthase (EC 5.4.99.6), the entC gene product of Escherichia coli, catalyzes the conversion of chorismate to isochorismate, the first step in the biosynthesis of the powerful iron-chelating agent enterobactin. A sequence-specific deletion method has been used to construct an EntC overproducer, which allows for the purification and characterization of the E. coli isochorismate synthase for the first time. The N-terminal sequence and the subunit molecular weight (43,000) of the polypeptide derived from SDS-polyacrylamide gel electrophoresis agree with those deduced from DNA sequence data. The enzyme is an active monomer with a native molecular weight of 42,000. It was shown that EntC alone is fully capable of catalyzing the interconversion of chorismate and isochorismate in both directions and the associated activity is not affected by EntA of the same biosynthetic pathway as has recently been speculated [Elkins, M. F., & Earhart, C. F. (1988) FEMS Microbiol. Lett. 56, 35; Liu, J., Duncan, K., & Walsh, C.T. (1989) J. Bacteriol. 171, 791; Ozenberger, B. A., Brickman, T.J., & McIntosh, M. A. (1989) J. Bacteriol. 171, 775]. The kinetic constants were determined with Km = 14 microM and kcat = 173 min-1 for chorismate in the forward direction and Km = 5 microM and kcat = 108 min-1 for isochorismate in the backward direction. The equilibrium constant for the reaction derived from the kinetic data is 0.56 with the equilibrium lying toward the side of chorismate, corresponding to a free energy difference of 0.36 kcal/mol between chorismate and isochorismate.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Subcloning of the enterobactin biosynthetic gene entB: expression, purification, characterization, and substrate specificity of isochorismatase.

The Escherichia coli entB gene, coding for the enterobactin biosynthetic enzyme isochorismatase, has been subcloned into the multicopy plasmid pKK223-3 under the control of the tac promoter. The resulting recombinant plasmid pFR1 expresses isochorismatase amounting to over 50% of the total cellular protein. The enzyme has been purified to homogeneity and a convenient assay developed. The enzyme has a Km for isochorismate of 14.7 microM and a turnover number of 600 min-1. By use of 1H NMR spectroscopy, the progress of the reaction was followed with the expected formation of 2,3-dihydro-2,3-dihydroxybenzoate product. Several substrate analogues were also utilized by the enzyme including chorismic acid, the immediate precursor to isochorismic acid in the enterobactin biosynthetic pathway.

Base Sequence↗