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Biomedical subjects

A G Simpson

Publications and source records attributed to A G Simpson.

10 recordsLinked to original sources
PubMed2001

Evolutionary relationships among "jakobid" flagellates as indicated by alpha- and beta-tubulin phylogenies.

Jakobids are free-living, heterotrophic flagellates that might represent early-diverging mitochondrial protists. They share ultrastructural similarities with eukaryotes that occupy basal positions in molecular phylogenies, and their mitochondrial genome architecture is eubacterial-like, suggesting a close affinity with the ancestral alpha-proteobacterial symbiont that gave rise to mitochondria and hydrogenosomes. To elucidate relationships among jakobids and other early-diverging eukaryotic lineages, we characterized alpha- and beta-tubulin genes from four jakobids: Jakoba libera, Jakoba incarcerata, Reclinomonas americana (the "core jakobids"), and Malawimonas jakobiformis. These are the first reports of nuclear genes from these organisms. Phylogenies based on alpha-, beta-, and combined alpha- plus beta-tubulin protein data sets do not support the monophyly of the jakobids. While beta-tubulin and combined alpha- plus beta-tubulin phylogenies showed a sister group relationship between J. libera and R. americana, the two other jakobids, M. jakobiformis and J. incarcerata, had unclear affinities. In all three analyses, J. libera, R. americana, and M. jakobiformis emerged from within a well-supported large "plant-protist" clade that included plants, green algae, cryptophytes, stramenopiles, alveolates, Euglenozoa, Heterolobosea, and several other protist groups, but not animals, fungi, microsporidia, parabasalids, or diplomonads. A preferred branching order within the plant-protist clade was not identified, but there was a tendency for the J. libera-R. americana lineage to group with a clade made up of the heteroloboseid amoeboflagellates and euglenozoan protists. Jakoba incarcerata branched within the plant-protist clade in the beta- and the combined alpha- plus beta-tubulin phylogenies. In alpha- tubulin trees, J. incarcerata occupied an unresolved position, weakly grouping with the animal/fungal/microsporidian group or with amitochondriate parabasalid and diplomonad lineages, depending on the phylogenetic method employed. Tubulin gene phylogenies were in general agreement with mitochondrial gene phylogenies and ultrastructural data in indicating that the "jakobids" may be polyphyletic. Relationships with the putatively deep-branching amitochondriate diplomonads remain uncertain.

Animals↗
PubMed2001

Oxymonads are closely related to the excavate taxon Trimastix.

Despite intensive study in recent years, large-scale eukaryote phylogeny remains poorly resolved. This is particularly problematic among the groups considered to be potential early branches. In many recent systematic schemes for early eukaryotic evolution, the amitochondriate protists oxymonads and Trimastix have figured prominently, having been suggested as members of many of the putative deep-branching higher taxa. However, they have never before been proposed as close relatives of each other. We amplified, cloned, and sequenced small-subunit ribosomal RNA genes from the oxymonad Pyrsonympha and from several Trimastix isolates. Rigorous phylogenetic analyses indicate that these two protist groups are sister taxa and are not clearly related to any currently established eukaryotic lineages. This surprising result has important implications for our understanding of cellular evolution and high-level eukaryotic phylogeny. Given that Trimastix contains small, electron-dense bodies strongly suspected to be derived mitochondria, this study constitutes the best evidence to date that oxymonads are not primitively amitochondriate. Instead, Trimastix and oxymonads may be useful organisms for investigations into the evolution of the secondary amitochondriate condition. All higher taxa involving either oxymonads or Trimastix may require modification or abandonment. Affected groups include four contemporary taxa given the rank of phylum (Metamonada, Loukozoa, Trichozoa, Percolozoa), and the informal excavate taxa. A new "phylum-level" taxon may be warranted for oxymonads and Trimastix.

Animals↗
PubMed1987

Personnel services.

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Personnel Management↗
PubMed1983

Esophageal acid perfusion in coronary artery disease. Induction of myocardial ischemia.

Although coronary artery disease and gastroesophageal reflux disease are common conditions which, therefore, may coexist, it is unknown whether or not the presence of one affects the other. We performed esophageal acid perfusion tests, with concurrent blood pressure, heart rate, and 12-lead electrocardiographic monitoring, in 37 patients, 25 with angiographically documented coronary disease and 12 with normal coronary arteries. Rate-pressure product, an index of myocardial work load, was calculated. In patients with coronary disease who developed chest pain during acid perfusion, rate-pressure product increased from 10.0 +/- 1.0 x 10(3) (mean +/- SEM) basally to 15.2 +/- 1.5 x 10(3) (p less than 0.001), and 3 of 9 patients showed concomitant electrocardiogram evidence of myocardial ischemia. In addition, in coronary disease, 64% of patients with infrequent or absent reflux symptoms by history had positive acid perfusion tests, and 56% of patients with coronary disease who developed pain during esophageal acid perfusion could not distinguish that pain from their usual angina. We conclude that in coronary disease, acid perfusion (and, presumably, gastroesophageal reflux) resulting in chest pain causes rate-pressure product elevation and can induce myocardial ischemia. The presence of esophageal acid sensitivity is not accurately predicted by clinical history in coronary disease, and pain of esophageal origin is often confused with angina.

Angina Pectoris↗
PubMed1981

Radionuclide angiographic assessment of left ventricular function during exercise in patients with a severely reduced ejection fraction.

To study the effect of exercise on left ventricular ejection fraction in patients with congestive cardiomyopathy and the relation of the response to the origin of the myocardial dysfunction, 30 patients with a severely reduced ejection fraction (30 percent or less) were evaluated with radionuclide angiography. Group I consisted of 16 patients with ischemic cardiomyopathy and a mean (+/- standard deviation) resting ejection fraction of 22.3 +/- 6.1 percent. Group II was composed of 14 patients with primary cardiomyopathy and a mean resting ejection fraction of 19.3 +/- 4.7 percent. The mean age, left ventricular end-diastolic pressure, cardiac index and resting left ventricular ejection fraction of Groups I and II were similar; however, the change in the ejection fraction during similar levels of exercise differed significantly. The mean exercise ejection fraction decreased to 16.7 +/- 6.8 percent in Group I, but increased to 24.6 +/- 6.4 percent in Group II (p less than 0.001). Thus, exercise usually results in a directionally opposite change in left ventricular ejection fraction depending on the origin of the congestive cardiomyopathy.

Adult↗
PubMed1980

Role of aminophylline in refractory heart failure: a comparison to the vasodilator sodium nitroprusside, the old and the new.

Aminophylline [(theophylline ethylene diamine (TED)] reportedly improved cardiac hemodynamics by lowering vascular resistances and increasing contractility. TED as used clinically has not been compared to the vasodilator sodium nitroprusside (NP). To assess the relative hemodynamic effects of these two commonly used agents, the following comparison was made. Ten patients with congestive cardiomyopathy in chronic refractory heart failure [New York Heart Association (NYHA) class IV] were studied. All patients demonstrated cardiomegaly by chest x ray and echocardiography (LVd = 6.3 +/- 0.7 cm) and markedly abnormal hemodynamics during baseline observations (see Table I). Hemodynamic measurements at baseline were compared after TED infusion (mean blood level = 16 +/- 12 micrograms/m/TED) and during intravenous NP. No significant changes in heart rate occurred during either therapeutic intervention; a fall in mean arterial pressure of 10 mmHg (p < 0.01) was observed during NP therapy; atrioventricular (AV) block with ventricular fibrillation was successfully treated in one patient after TED. Theophylline ethylene diamine demonstrated no detectable cardiac hemodynamic effects 60--90 min post infusion despite proven blood levels, whereas NP exhibited distinctly beneficial effects in this patient group. Previous studies demonstrating improved hemodynamics occurring with TED have been limited to the time of infusion or within the following 40 min, a time when TED blood levels are maximum and therefore closest to toxicity. The results of this study suggest that TED demonstrates no beneficial hemodynamic effects in refractory heart failure as early as 1 h after infusion despite blood levels in the therapeutic range.

Aged↗
PubMed1978

Kinetoplast RNA of Leishmania tarentolae.

RNA has been isolated from highly purified kinetoplast-mitochondrial fractions of Leishmania tarentolae, and shown to consist of two major species that sediment at 9S and 12S in sucrose and also several additional low molecular weight species which were visualized by gel electrophoresis. The in vivo transcription of 9S and 12S RNAs was inhibited by ethidium bromide and rifampin, and was fairly insensitive to low actinomycin D and camptothecin. The 9S and 12S RNAs were isolated by acrylamide gel electrophoresis or by sedimentation in sucrose. Both RNAs contained approximately 80% A + U and did not contain long stretches of poly(A). The 9S and 12S RNAs were found to hybridize selectively to the maxicircle sequences of the kinetoplast DNA, implying that the maxicircle, and not the minicircle, represents the informational mitochondrial DNA in the kinetoplast.

Animals↗
PubMedDate not supplied

On core jakobids and excavate taxa: the ultrastructure of Jakoba incarcerata.

The cellular organisation of the 'excavate' flagellate Jakoba incarcerata Bernard, Simpson and Patterson 2000 is described. Cells have one nucleus and dictyosome. The putative mitochondria lack cristae. Two flagella (anterior and posterior) insert anterior to the feeding groove. The posterior flagellum bears a dorsal vane. An 'anterior' microtubular root arises against the anterior basal body. Two main microtubular roots, left and right, and a singlet 'root' arise around the posterior basal body and support the groove. Non-microtubular fibres termed 'A', 'B', 'I', and 'composite' associate with the right root. A multilaminar 'C' fibre associates with the left root. The cytoskeleton of J. incarcerata indicates a common ancestry with other excavate taxa (i.e. diplomonads, retortamonads, heteroloboseids, 'core jakobids', Malawimonas, Carpediemonas, and Trimastix). Overall, J. incarcerata is most similar to (other) core jakobids, namely Jakoba libera, Reclinomonas, and Histiona. We regard J. incarcerata as a core jakobid and identify the group by the synapomorphy 'vanes restricted to dorsal side of the posterior flagellum'. The anterior root and position of the B fibre (and presence of dense inclusions in the cartwheels and a conscpicuous singlet root-associated fibre) in J. incarcerata are novel for core jakobids and argue for close relationships with Trimastix and/or Heterolobosea. The C fibre is similar in substructure to the costal fibre of parabasalids and it is possible that the structures are homologous.

Animals↗