Decoding and Analysis of the Crown-of-Thorns Starfish Acanthaster planci Genome

Echinoderms are at the base of the deuterostome clade, yet have radial body plans, a watervascular system, and exoskeletons. In order to investigate how genomes control development, I studied the “Crown-of-Thorns Starfish” (COTS) or Acanthaster planci genome. I made four discoveries from sequencing two COTS specimens, one from the Great Barrier Reef, Australia (‘GBR’) and the other from Okinawa, Japan (‘OKI’). Separate 384 megabase (Mb) assemblies containing ~24,500 genes were generated. First, I discovered that both genomes displayed unexpectedly low heterozygosity; reciprocal BLAST alignment of scaffolds longer than 10 kilobases (Kb) revealed 98.8% nucleotide identity, consistent with a single pacific COTS clade undergoing a recent population expansion. Second, although the unique Hox gene order in sea urchins was hypothesized to be related to pentaradial body plans, I discovered that COTS Hox and ParaHox clusters resemble hemichordate and chordate clusters. The COTS Hox cluster shares with sea urchins the transposition of even-skipped (Evx), as well as posterior Hox reorganization. I thus proposed an evolutionary scenario for how shuffling of the Hox cluster in urchins may have arisen. Third, recent studies show that hemichordates possess a deuterostome-specific cluster of transcription factors associated with development of pharyngeal gill slits. Although extant echinoderms do not have pharyngeal gill slits, I found the cluster in the COTS genome, supporting an ancient origin for pharyngeal gill slits as a deuterostome-defining morphological feature. Fourth, using systems biology notation, I mapped COTS candidate genes for 1-methlyadenine (1-MA)-mediated oocyte maturation. This thesis confirms that the high quality of the COTS genome is biologically significant, and amendable to future studies. Although COTS are famous for decimating coral reefs, this thesis shows that COTS can also be used for genomic and evolutionary developmental research.Okinawa Institute of Science and Technology Graduate Universit

2,4-Dinitrophenylhydrazones of 2,4-dihydroxybenzaldehyde, 2,4-dihydroxyacetophenone and 2,4-dihydroxybenzophenone

In 2,4-dihydroxybenzaldehyde 2,4-dinitrophenylhydrazone N,N-dimethylformamide solvate (or 4-[(2,4-dinitrophenyl)-hydrazonomethyl]benzene-1,3-diol N,N-dimethylformamide solvat

Acute nifedipine withdrawal: Consequences of preoperative and late cessation of therapy in patients with prior unstable angina

Reports of acute ischemic events after withdrawal of calcium antagonist therapy in outpatients and during bypass surgery in patients with prior angina at rest prompted the examination of the effect of nifedipine withdrawal in 81 patients who had completed a prospective, double-blind randomized trial of nifedipine versus placebo for rest angina. Thirty-nine patients underwent bypass surgery for uncontrolled angina or left main coronary artery disease. No significant difference between patients withdrawn from nifedipine or placebo was seen in the incidence of perioperative myocardial infarction, hypotension requiring intraaortic balloon counterpulsation, vasopressor or vasodilator requirements or incidence of significant arrhythmias.An additional 42 patients had completed 2 years on a protocol consisting of nitrates and propranolol in addition to nifedipine or placebo. During a mean of 66 hours of continuous monitoring after withdrawal of nifedipine or placebo, heart rate and blood pressure were unchanged. A worsening of previously present angina at rest occurred in five patients who had continued to experience rest angina before drug withdrawal, four of whom were withdrawn from nifedipine. No patient with class I to III angina experienced new onset of rest angina during drug withdrawal. No patient experienced myocardial infarction. There was no significant difference between patients withdrawn from nifedipine or placebo in the duration or frequency of ischemic ST changes on continuous electrocardiographic monitoring, or in duration or positive results of serial exercise treadmill testing.Thus, no early adverse effects of acute nifedipine withdrawal were found in patients with prior rest angina at the time of bypass surgery or in stable patients receiving long-term medical therapy. Patients with continued symptoms of rest angina, however, may experience adverse ischemic events with nifedipine withdrawal

Significant CD4, CD8, and CD19 Lymphopenia in Peripheral Blood of Sarcoidosis Patients Correlates with Severe Disease Manifestations

BACKGROUND: Sarcoidosis is a poorly understood chronic inflammatory condition. Infiltration of affected organs by lymphocytes is characteristic of sarcoidosis, however previous reports suggest that circulating lymphocyte counts are low in some patients with the disease. The goal of this study was to evaluate lymphocyte subsets in peripheral blood in a cohort of sarcoidosis patients to determine the prevalence, severity, and clinical features associated with lymphopenia in major lymphocyte subsets. METHODOLOGY/PRINCIPAL FINDINGS: Lymphocyte subsets in 28 sarcoid patients were analyzed using flow cytometry to determine the percentage of CD4, CD8, and CD19 positive cells. Greater than 50% of patients had abnormally low CD4, CD8, or CD19 counts (p<4x10(-10)). Lymphopenia was profound in some cases, and five of the patients had absolute CD4 counts below 200. CD4, CD8, and CD19 lymphocyte subset counts were significantly correlated (Spearman's rho 0.57, p = 0.0017), and 10 patients had low counts in all three subsets. Patients with severe organ system involvement including neurologic, cardiac, ocular, and advanced pulmonary disease had lower lymphocyte subset counts as a group than those patients with less severe manifestations (CD4 p = 0.0043, CD8 p = 0.026, CD19 p = 0.033). No significant relationships were observed between various medical therapies and lymphocyte counts, and lymphopenia was present in patients who were not receiving any medical therapy. CONCLUSIONS/SIGNIFICANCE: Significant lymphopenia involving CD4, CD8, and CD19 positive cells was common in sarcoidosis patients and correlated with disease severity. Our findings suggest that lymphopenia relates more to disease pathology than medical treatment

Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure

Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure.BackgroundPatients with acute renal failure (ARF) have high morbidity and mortality rates, particularly if they have serious comorbid conditions. Several studies indicate that in rats with ARF caused by ischemia or certain nephrotoxins, insulin-like growth factor-I (IGF-I) enhances the recovery of renal function and suppresses protein catabolism.MethodsOur objective was to determine whether injections of recombinant human IGF-I (rhIGF-I) would enhance the recovery of renal function and is safe in patients with ARF. The study was designed as a randomized, double-blind, placebo-controlled trial in intensive care units in 20 teaching hospitals. Seventy-two patients with ARF were randomized to receive rhIGF-I (35 patients) or placebo (37 patients). The most common causes of ARF in the rhIGF-I and placebo groups were, respectively, sepsis (37 and 35% of patients) and hypotension or hemodynamic shock (42 and 27% of patients). At baseline, the mean (± sd) APACHE II scores in the rhIGF-I and placebo-treated groups were 24 ± 5 and 25 ± 8, respectively. In the rhIGF-I and placebo groups, the mean (median) urine volume and urinary iothalamate clearances (glomerular filtration rate) were 1116 ± 1037 (887) and 1402 ± 1183 (1430)ml/24hr and 6.4 ± 5.9 (4.3) and 8.7 ± 7.2 (4.4)ml/min and did not differ between the two groups. Patients were injected subcutaneously every 12hours with rhIGF-I, 100 μg/kg desirable body weight, or placebo for up to 14days. Injections were started within six days of the onset of ARF. The primary end-point was a change in glomerular filtration rate from baseline. Other end points included changes from baseline in urine volume, creatinine clearance and serum urea, creatinine, albumin and transferrin, frequency of hemodialysis or ultrafiltration, and mortality rate.ResultsDuring the treatment period, which averaged 10.7 ± 4.1 and 10.6 ± 4.5days in the rhIGF-I and placebo groups, there were no differences in the changes from baseline values of the glomerular filtration rate, creatinine clearance, daily urine volume, or serum urea nitrogen, creatinine, albumin or transferrin. In patients who did not receive renal replacement therapy, there was also no significant difference in serum creatinine and urea between the two groups. Twenty patients in the rhIGF-I group and 17 placebo-treated patients underwent dialysis or ultrafiltration. Twelve rhIGF-I–treated patients and 12 placebo-treated patients died during the 28days after the onset of treatment.ConclusionsrhIGF-I does not accelerate the recovery of renal function in ARF patients with substantial comorbidity

Nuggets, Pearls, and Vignettes of Master Heart Failure Clinicians

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73696/1/j.1527-5299.2001.00307.x.pd

Hemichordate genomes and deuterostome origins

Acorn worms, also known as enteropneust (literally, ‘gut-breathing’) hemichordates, are marine invertebrates that share features with echinoderms and chordates. Together, these three phyla comprise the deuterostomes. Here we report the draft genome sequences of two acorn worms, Saccoglossus kowalevskii and Ptychodera flava. By comparing them with diverse bilaterian genomes, we identify shared traits that were probably inherited from the last common deuterostome ancestor, and then explore evolutionary trajectories leading from this ancestor to hemichordates, echinoderms and chordates. The hemichordate genomes exhibit extensive conserved synteny with amphioxus and other bilaterians, and deeply conserved non-coding sequences that are candidates for conserved gene-regulatory elements. Notably, hemichordates possess a deuterostome-specific genomic cluster of four ordered transcription factor genes, the expression of which is associated with the development of pharyngeal ‘gill’ slits, the foremost morphological innovation of early deuterostomes, and is probably central to their filter-feeding lifestyle. Comparative analysis reveals numerous deuterostome-specific gene novelties, including genes found in deuterostomes and marine microbes, but not other animals. The putative functions of these genes can be linked to physiological, metabolic and developmental specializations of the filter-feeding ancestor