Antiparkinsonian drugs as potent contributors to nocturnal sleep in patients with Parkinson's disease.

OBJECTIVE: To clarify whether antiparkinsonian drugs contribute to nocturnal sleep disturbances in patients with Parkinson's disease (PD). BACKGROUND: Although the major antiparkinsonian drugs L-dopa and dopamine agonists (DAs) have been found to affect sleep, little is known about the effects of specific drugs on sleep in PD patients. METHODS: The study participants consisted of 112 PD patients (median age 72.5 years [inter-quartile range: IQR 65-79]; mean disease duration 8.44 years [standard deviation: 7.33]; median Hoehn and Yahr stage 3 [IQR 2-3.75]) taking one of three types of non-ergot extended-release DAs (rotigotine 32; pramipexole 44; ropinirole 36) with or without L-dopa (median daily total dosage of antiparkinsonian drugs 525.5 mg [IQR 376.25-658] levodopa equivalent dose [LED]). Participants were assessed using the PD Sleep Scale-2 (PDSS-2). RESULTS: For the whole PD patient cohort, the PDSS-2 sleep disturbance domain score and the scores for item 1 assessing sleep quality and item 8 assessing nocturia were positively correlated with daily total dosage of antiparkinsonian drugs and dosage of L-dopa, but not with the dosage of DAs. Sub-analysis according to DA treatment revealed that DA dosage was not correlated with item 1 or 8 score in any of the subgroups. The LED ratio of rotigotine to the total dosage of antiparkinsonian drugs was inversely correlated with the item 1 score. CONCLUSIONS: These data suggest that antiparkinsonian drugs, in particular L-dopa, adversely affect nocturnal sleep in PD patients, especially in terms of sleep quality and nocturia. Thus, adjusting both the total dosage of antiparkinsonian drugs and the dose-ratio of L-dopa might be key actions for alleviating poor sleep quality in patients with PD. Among DAs, we found a clear positive correlation between the dose-ratio of rotigotine and sleep quality. Thus, partial L-dopa replacement with rotigotine could improve sleep quality in patients with PD.

Light and electron microscopic observations of the reproductive swarmer cells of nassellarian and spumellarian polycystines (Radiolaria).

We observed reproductive swarmer cells of the nassellarian and spumellarian polycystine radiolarians Didymocyrtis ceratospyris, Pterocanium praetextum, Tetrapyle sp., and Triastrum aurivillii using light, scanning and transmission electron microscopy. The swarmer cells had subspherical to ovoid or spindle shapes with two unequal flagella tapered to whip-like ends. The cell size was approximately 2.5-5.5µm long and 1.6-2.2µm wide, which is significantly smaller than that of the collodarian (colonial or naked) polycystine radiolarians. Transmission electron microscopy revealed that the swarmer cells possessed a nucleus, mitochondria with tubular cristae, Golgi body, and small lipid droplets in the cytoplasm; they also had a large vacuole in which a single crystalline inclusion (approx. 1.0-1.5µm) that was probably celestite (SrSO4) was enclosed. The swarmer cells were released directly from the parent cells. At that time, morphological change such as encystment was not observed in the parent cells, and the axopodia remained extended in a period of swarmer reproduction for floating existence. This may have prevented the polycystine swarmers from rapidly sinking down to great depths. Thus, we concluded that the polycystine radiolarians release the swarmer cells into the photic layer in the same way as the symbiotic acantharians.

Gymnoxanthella radiolariae gen. et sp. nov. (Dinophyceae), a dinoflagellate symbiont from solitary polycystine radiolarians.

The symbiotic dinoflagellate Gymnoxanthella radiolariae T. Yuasa et T. Horiguchi gen. et sp. nov. isolated from polycystine radiolarians is described herein based on light, scanning and transmission electron microscopy as well as molecular phylogenetic analyses of SSU and LSU rDNA sequences. Motile cells of G. radiolariae were obtained in culture, and appeared to be unarmored. The cells were 9.1-11.4 µm long and 5.7-9.4 µm wide, and oval to elongate oval in the ventral view. They possessed an counterclockwise horseshoe-shaped apical groove, a nuclear envelope with vesicular chambers, cingulum displacement with one cingulum width, and the nuclear fibrous connective; all of these are characteristics of Gymnodinium sensu stricto (Gymnodinium s.s.). Molecular phylogenetic analyses also indicated that G. radiolariae belongs to the clade of Gymnodinium s.s. However, in our molecular phylogenetic trees, G. radiolariae was distantly related to Gymnodinium fuscum, the type species of Gymnodinium. Based on the consistent morphological, genetic, and ecological divergence of our species with the other genera and species of Gymnodinium s.s., we considered it justified to erect a new, separate genus and species G. radiolariae gen. et sp. nov. As for the peridinioid symbiont of radiolarians, Brandtodinium has been erected as a new genus instead of Zooxanthella, but the name Zooxanthella is still valid. Brandtodinium is a junior synonym of Zooxanthella. Our results suggest that at least two dinoflagellate symbiont species, peridinioid Zooxanthella nutricula and gymnodinioid G. radiolariae, exist in radiolarians, and that they may have been mixed and reported as "Z. nutricula" since the 19th century.

Ultrastructural morphology of the reproductive swarmers of Sphaerozoum punctatum (Huxley) from the East China Sea.

Reproductive swarmers of the polycystine radiolarian Sphaerozoum punctatum (Huxley) collected from the East China Sea were examined using light, scanning and transmission electron microscopy. The swarmer cells were about 8-10 µm in length with a pear-like shape and a conical end with two flagella. A nucleus, mitochondria, Golgi body, lipid droplets and, characteristically, a single, large, vacuole-bound SrSO4 crystal were present in the cytoplasm. Centering on the crystal inclusion, swarmers swam in a rapid rotational movement both clockwise and anticlockwise. Small subunit (SSU) rDNA sequences obtained for the reproductive swarmer cells from S. punctatum show a monophyletic group together with colonial spumellarians and grouped with S. punctatum from Bermuda in the clade. The morphological features and molecular phylogeny of the reproductive swarmers of S. punctatum show evidence of ancestral traits of radiolarians; acantharians and polycystines have a common ancestry. In addition, SrSO4 inclusion of the swarmer cell may be a form of ballast deposited by the swarmer to allow proper positioning in the water column. We hypothesize that radiolarian-affiliated sequences from SSU rDNA clone libraries of marine picoeukaryotes may be derived from the picoplanktonic cells of radiolarians; i.e., small flagellated life stages such as reproductive swarmers or gametes.

Molecular identification of reproductive cells released from Cypassis irregularis Nigrini (Radiolaria).

The mechanisms of the extensive distribution of radiolarian-affiliated sequences from clone libraries of marine picoeukaryotes from deeper water remain poorly understood. Here, we describe an event that could explain this phenomenon. A polycystine radiolarian species, Cypassis irregularis Nigrini, released a large number of pico-size cells under culture conditions. The diameters of the cells averaged ∼3 µm and the 18S rDNA sequences fell within those of typical radiolarian families. This finding suggests that the radiolarian sequences found in the picoeukaryote size fraction from deep water are from swarmers or gametes released for reproduction. Thus, the deep ocean is expected to aid in the widespread dispersal of the genetic material of eukaryotes.

Genome-wide identification and characterization of transcripts translationally regulated by bacterial lipopolysaccharide in macrophage-like J774.1 cells.

Although Escherichia coli LPS is known to elicit various proinflammatory responses in macrophages, its effect on the translational states of transcripts has not yet been explored on a genome-wide scale. To address this, we investigated the mRNA profiles in polysomal and free messenger ribonucleoprotein particle (mRNP) fractions of mouse macrophage-like J774.1 cells, using Affymetrix Mouse Genome 430 2.0 GeneChips. Comparison of the mRNA profiles in total cellular, polysomal, and free mRNP fractions enabled us to identify transcripts that were modulated at the translational level by LPS: among 19,791 transcripts, 115 and 418 were up- and downregulated at 1, 2, or 4 h after LPS stimulation (100 ng/ml) in a translation-dependent manner. Interestingly, gene ontology-based analysis suggested that translation-dependent downregulated genes frequently include those encoding proteins in the mitochondrial respiratory chain. In fact, the mRNA levels of some transcripts for complexes I, IV, and V in the mitochondrial respiratory chain were translationally downregulated, eventually contributing to the decline of their protein levels. Moreover, the amount of metabolically labeled cytochrome oxidase subunit Va in complex IV was decreased without any change of its mRNA level in total cellular fraction after LPS stimulation. Consistently, the total amounts and activities of complexes I and IV were attenuated by LPS stimulation, and the attenuation was independent of nitric oxide. These results demonstrated that translational suppression may play a critical role in the LPS-mediated attenuation of mitochondrial oxidative phosphorylation in a nitric oxide-independent manner in J774.1 cells.

Molecular diversity of alveolates associated with neritic north atlantic radiolarians.

Seven species of polycystine radiolarians and one phaeodarian species were investigated in order to determine the diversity of their associate organisms and their species specificity. Twelve partial 18S ribosomal DNA (rDNA) sequences were obtained showing a high diversity of associates, both within spumellarian and nassellarian radiolarians and among species. Two of the sequences obtained are highly similar to Scrippsiella, a dinoflagellate genus already reported as a symbiont of polycystine radiolarians. Nine of the new 18S rDNA sequences group with various alveolates. Some of these groups include parasites, such as the lethal endoparasite Amoebophrya, while others consist of non-annotated novel organisms found worldwide in various types of marine environments. We also obtained a sequence from a bacillariophytan highly similar to the 18S rDNA of the diatom species Diatoma tenue, which may derive from radiolarian food. Additionally, this is the first study to report on a phaeodarian associate.