Biomedical subjects

Kathleen M Shannon

Publications and source records attributed to Kathleen M Shannon.

5 recordsLinked to original sources

PubMed2005

Abundant neuritic inclusions and microvacuolar changes in a case of diffuse Lewy body disease with the A53T mutation in the alpha-synuclein gene.

We report here a case of diffuse Lewy body disease with the A53T mutation in the alpha-synuclein gene. The proband presented at the age of 41 years with parkinsonism that was poorly responsive to levodopa. She subsequently developed cognitive impairment and moderate dementia, and died at the age of 50. Her father, paternal grandfather and uncle were all reported to have suffered from Parkinson's disease. Staining of tissue sections from the proband's brain with hematoxylin-eosin and alpha-synuclein antibodies showed small numbers of Lewy bodies in a few brain regions. This contrasted with large numbers of Lewy neurites and neuroaxonal spheroids in many brain regions. By electron microscopy, Lewy neurites consisted of abnormal filaments and dense granular material. Isolated filaments resembled those previously described in idiopathic Parkinson's disease and dementia with Lewy bodies. They were decorated by antibodies specific for the N and C termini of alpha-synuclein, indicating the presence of the full-length protein. Nucleus accumbens and the lower layers in limbic areas of the cerebral cortex showed prominent vacuolation, with frequent clustering of microvacuoles around Lewy neurites. Nerve cell loss was most extensive in dorsal motor nucleus of the vagus nerve, substantia nigra and nucleus basalis of Meynert. Neurofibrillary tangles and senile plaques were not observed. However, in several brain regions, a few widely scattered tau-positive nerve cell bodies and neurites were present. By electron microscopy, Alzheimer-type paired helical and straight filaments were seen.

Adult↗

PubMed2005

Hemiballismus.

Hemiballismus is the most dramatic movement disorder seen in clinical practice. Its emergence points to a structural lesion or metabolic dysfunction in the region of the subthalamic nucleus, its afferent or efferent pathways, or interconnected deep brain nuclei, usually on the side contralateral to the movements. Any focal process may be to blame, but elderly sufferers generally have had vascular events, whereas the etiology is infectious or inflammatory in younger patients. Severe nonketotic hyperglycemia is another important cause of hemiballismus in the elderly. Hemiballismus patients require treatment both for the underlying etiology of the movement and for the movements themselves. There are no large controlled clinical trials to guide anti-ballismus therapy. However, dopamine receptor blocking agents have an established track record in suppressing choreic and ballistic movements, and are first-line agents for acute treatment. Standard neuroleptics such as haloperidol and perphenazine are started at low doses and titrated as tolerated until the movements are controlled. Atypical antipsychotics such as risperidone and clozapine have been used in small series and may have a reduced risk of extrapyramidal side effects. Catecholamine-depleting agents such as reserpine and tetrabenazine may be considered when long-term therapy is required. Other pharmacologic agents have met with varying success. The course of hemiballismus may be complicated by exhaustion, injury, or metabolic disorders, but with good supportive care, acute survival is good, and long-term survival reflects the prognosis of the underlying etiology. In time, the ballistic movements themselves tend to subside allowing withdrawal of drugs in many cases. When movements persist, stereotactic functional neurosurgical procedures may be considered in good surgical candidates.

Journal Article↗

PubMed2003

A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease.

Thirty-four patients with advanced Parkinson's disease participated in a prospective 24-month double-blind, placebo-controlled trial of fetal nigral transplantation. Patients were randomized to receive bilateral transplantation with one or four donors per side or a placebo procedure. The primary end point was change between baseline and final visits in motor component of the Unified Parkinson's Disease Rating Scale in the practically defined off state. There was no significant overall treatment effect (p = 0.244). Patients in the placebo and one-donor groups deteriorated by 9.4 +/- 4.25 and 3.5 +/- 4.23 points, respectively, whereas those in the four-donor group improved by 0.72 +/- 4.05 points. Pairwise comparisons were not significant, although the four-donor versus placebo groups yielded a p value of 0.096. Stratification based on disease severity showed a treatment effect in milder patients (p = 0.006). Striatal fluorodopa uptake was significantly increased after transplantation in both groups and robust survival of dopamine neurons was observed at postmortem examination. Fifty-six percent of transplanted patients developed dyskinesia that persisted after overnight withdrawal of dopaminergic medication ("off"-medication dyskinesia). Fetal nigral transplantation currently cannot be recommended as a therapy for PD based on these results.

Adult↗

PubMed2002

An R5L tau mutation in a subject with a progressive supranuclear palsy phenotype.

MAPT, the gene encoding tau, was screened for mutations in 96 progressive supranuclear palsy subjects. A point mutation (R5L) was identified in a single progressive supranuclear palsy subject that was not in the other progressive supranuclear palsy subjects or in 96 controls. Functionally, this mutation alters the ability of tau to promote microtubule assembly. Analysis of soluble tau from different brain regions indicates that the mutation does not affect the ratio of tau isoforms synthesized. Aggregated insoluble tau from subcortical regions was predominantly four-repeat tau with no or one amino terminal insert (0N4R and 1N4R). Insoluble tau from cortical regions also contained 1N3R tau. Thus, the R5L mutation causes a progressive supranuclear palsy phenotype, presumably by a gain-of-function mechanism.

Amino Acid Sequence↗

PubMed2002

Serum SP-D is a marker of lung injury in rats.

Pulmonary surfactant protein D (SP-D) is expressed in alveolar type II and bronchiolar epithelial cells and is secreted into alveoli and conducting airways. However, SP-D has also been measured in serum and is increased in patients with acute respiratory distress syndrome, pulmonary fibrosis, and alveolar proteinosis. To demonstrate that SP-D can be measured in rat serum, we instilled rats with keratinocyte growth factor, which produces type II cell hyperplasia and an increase in SP-D in bronchoalveolar lavage fluid (BALF). To evaluate serum SP-D as a biomarker of lung injury, we examined several injury models. In rats treated with 1 unit of bleomycin, serum SP-D was elevated on days 3, 7, 14, and 28 after instillation, and SP-D mRNA was increased in focal areas as detected by in situ hybridization. However, there was no increase in whole lung SP-D mRNA when the expression was normalized to whole lung 18S rRNA. After instillation of 2 units of bleomycin, the serum levels of SP-D were higher, and SP-D was also increased in BALF and lung homogenates. In another model of subacute injury, serum SP-D was increased in rats treated with paraquat plus oxygen. Finally to evaluate acute lung injury, we instilled rats with HCl; SP-D was increased at 4 h after instillation. Our data indicate that serum SP-D may be a useful indicator of lung injury and type II cell hyperplasia in rats.

Animals↗