Biomedical subjects

Paul Shanahan

Publications and source records attributed to Paul Shanahan.

8 recordsLinked to original sources

PubMed2006

Post-traumatic stress disorder and diabetes: co-morbidity and outcomes in a male veterans sample.

The purpose of this study was to assess the prevalence and correlates of comorbid diabetes and Post-Traumatic Stress disorder(PTSD)and potential relationships between PTSD and diabetes outcomes. Male patients enrolled in a VA primary care database (N = 73,270) were classified as having diabetes from pharmacy records (N = 14,438) and grouped into those with diagnoses of PTSD with depression (N = 649), PTSD-only (N = 480), Depression-only (N = 1696), Other psychiatric diagnosis (N = 736), or No psychiatric diagnosis (N = 10,877) based on the Purpose of Visit diagnoses in the medical record. Outcomes included glycemic control (HbA1c), cholesterol and triglycerides. Correlates were age, substance use disorder, other psychiatric diagnosis, number of primary care encounters, and medications. The prevalence of comorbid diabetes and PTSD was 8% (n = 1129). Of these, 57% (n = 649) had comorbid depression. Patients with PTSD and depression had higher rates of substance use disorder and higher cholesterol and LDL. Patients with depression had poorer glycemic control. Patients with PTSD and depression weighed more and had higher BMI than patients with neither diagnosis. Thus, male diabetes patients with PTSD and depression may be vulnerable to substance use disorders and to weight/lipid problems that can affect health. Depression is a likely contributor to poor glycemic control. Careful screening for mental health comorbidities is needed for diabetes patients.

Aged↗

PubMed2006

Reduction of intracortical inhibition in soleus muscle during postural activity.

Short-interval intracortical inhibition (SICI) decreases during voluntary contraction of the target muscle. It is unknown whether this effect also occurs with postural contractions. We have compared the effects of voluntary and postural contractions on SICI in the soleus (SOL) muscle. We applied transcranial magnetic stimuli (TMS) in subjects under three tasks: sitting at rest (Rest), sitting while activating the SOL muscle (Voluntary), or standing quietly (Postural). In control trials, we applied suprathreshold TMS to obtain unconditioned motor-evoked potentials (MEPs). In test trials, the same TMS was preceded by a subthreshold TMS at different interstimulus intervals (ISIs), to obtain a conditioned MEP. SICI and intracortical facilitation (ICF) were expressed as the decrease or increase in MEP size relative to unconditioned MEPs. There was significant effect of task in mean SICI or mean ICF in SOL. Mean SICI in SOL was 52% in Rest and decreased to 21% in Voluntary and 15% in Postural. Mean ICF in SOL was 132% and decreased to 113% in Voluntary and to 108% in Postural. Mean SICI in SOL was not different in Voluntary and Postural tasks. There was no effect of task in mean SICI or mean ICF in TA. Our results indicate that decrease of SICI with muscle contraction occurs to a similar extent with tonic voluntary and postural activation, suggesting that those contractions require a similar type of cortical involvement. However, it cannot be excluded that some part of the SICI reduction with muscle contraction depends on changes in segmental excitability.

Adult↗

PubMed2006

Stress, emotion and the heart: tako-tsubo cardiomyopathy.

Tako-tsubo cardiomyopathy is a cardiac syndrome precipitated by profound emotional stress and anxiety, particularly in middle-aged women. It presents as a mimic of acute myocardial infarction, but coronary angiography shows normal coronary arteries and a characteristic left ventriculogram resembling an "octopus pot". The condition seems to have a favourable prognosis. Initially described in Japan, and with many names in the literature, it is being increasingly recognised in the West owing to early coronary angiography and primary coronary intervention, accounting for up to 1 in 30 primary cases of angioplasty in some institutions. A typical case is described, and the clinical features, pathophysiology and management reviewed.

Aged↗

PubMed2003

The ipsilateral human motor cortex can functionally compensate for acute contralateral motor cortex dysfunction.

What promotes motor recovery from stroke? To date, studies of recovery from stroke have shown alterations in function in various cortical areas, including the contralesional (unaffected) motor cortex (M1). However, whether these changes contribute to recovery or are mere epiphenomena remains unclear. We therefore sought evidence that the ipsilateral M1 can compensate for dysfunction of the contralateral M1. We recorded the change in force production during a finger-tapping task in response to acute disruption of M1 function by repetitive transcranial magnetic stimulation (rTMS). Neither control (occipital) nor ipsilateral M1 rTMS lead to a change in tapping force. RTMS over contralateral M1 had a short-lived effect and induced changes in ipsilateral M1 excitability around the time that these behavioral effects abated, consistent with delayed compensation by the ipsilateral M1. Simultaneous bilateral M1 stimulation, designed to prevent compensation by the ipsilateral M1, had a large and prolonged effect on tapping force. This is the first demonstration that the ipsilateral primary motor cortex is capable of functionally significant compensation for focal contralateral cortical dysfunction in the adult human and provides a rational basis for interventional treatments aimed at promoting functional compensation in unaffected cortical areas after stroke.

Biomechanical Phenomena↗

PubMed2003

The endogenous Mus81-Eme1 complex resolves Holliday junctions by a nick and counternick mechanism.

Functional studies strongly suggest that the Mus81-Eme1 complex resolves Holliday junctions (HJs) in fission yeast, but in vitro it preferentially cleaves flexible three-way branched structures that model replication forks or 3' flaps. Here we report that a nicked HJ is the preferred substrate of endogenous and recombinant Mus81-Eme1. Cleavage occurs specifically on the strand that opposes the nick, resulting in resolution of the structure into linear duplex products. Resolving cuts made by the endogenous Mus81-Eme1 complex on an intact HJ are quasi-simultaneous, indicating that Mus81-Eme1 resolves HJs by a nick and counternick mechanism, with a large rate enhancement of the second cut arising from the flexible nature of the nicked HJ intermediate. Recombinant Mus81-Eme1 is ineffective at making the first cut. We also report that HJs accumulate in a DNA polymerase alpha mutant that lacks Mus81, providing further evidence that the Mus81-Eme1 complex targets HJs in vivo.

Cells, Cultured↗

PubMed2003

Fission yeast Mus81.Eme1 Holliday junction resolvase is required for meiotic crossing over but not for gene conversion.

Most models of homologous recombination invoke cleavage of Holliday junctions to explain crossing over. The Mus81.Eme1 endonuclease from fission yeast and humans cleaves Holliday junctions and other branched DNA structures, leaving its physiological substrate uncertain. We report here that Schizosaccharomyces pombe mus81 mutants have normal or elevated frequencies of gene conversion but 20- to 100-fold reduced frequencies of crossing over. Thus, gene conversion and crossing over can be genetically separated, and Mus81 is required for crossing over, supporting the hypothesis that the fission yeast Mus81.Eme1 protein complex resolves Holliday junctions in meiotic cells.

Crossing Over, Genetic↗

PubMed2003

Replication checkpoint kinase Cds1 regulates recombinational repair protein Rad60.

Genome integrity is protected by Cds1 (Chk2), a checkpoint kinase that stabilizes arrested replication forks. How Cds1 accomplishes this task is unknown. We report that Cds1 interacts with Rad60, a protein required for recombinational repair in fission yeast. Cds1 activation triggers Rad60 phosphorylation and nuclear delocalization. A Rad60 mutant that inhibits regulation by Cds1 renders cells specifically sensitive to replication fork arrest. Genetic and biochemical studies indicate that Rad60 functions codependently with Smc5 and Smc6, subunits of an SMC (structural maintenance of chromosomes) complex required for recombinational repair. These studies indicate that regulation of Rad60 is an important part of the replication checkpoint response controlled by Cds1. We propose that control of Rad60 regulates recombination events at stalled forks.

Amino Acid Sequence↗

PubMed2002

CDK phosphorylation of Drc1 regulates DNA replication in fission yeast.

Cyclin-dependent kinases (CDKs) are absolutely required for DNA replication in eukaryotic cells. CDKs are thought to activate one or more replication factors, but the identities of these proteins are unknown. Here we describe fission yeast Drc1, a protein required for DNA replication that is phosphorylated by Cdc2. Drc1 depletion leads to catastrophic mitotic divisions with incompletely replicated DNA, indicating that Drc1 is required for DNA synthesis and S-M replication checkpoint control. Drc1 associates with Cdc2 and is phosphorylated at the onset of S phase when Cdc2 is activated. Mutant Drc1 that lacks CDK phosphorylation sites is nonfunctional and fails to interact with Cut5 replication factor. These data suggest that Cdc2 promotes DNA replication by phosphorylating Drc1 and regulating its association with Cut5.

CDC2 Protein Kinase↗