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Biomedical subjects

J Eisen

Publications and source records attributed to J Eisen.

15 recordsLinked to original sources

Evolution of sensory complexity recorded in a myxobacterial genome.

Myxobacteria are single-celled, but social, eubacterial predators. Upon starvation they build multicellular fruiting bodies using a developmental program that progressively changes the pattern of cell movement and the repertoire of genes expressed. Development terminates with spore differentiation and is coordinated by both diffusible and cell-bound signals. The growth and development of Myxococcus xanthus is regulated by the integration of multiple signals from outside the cells with physiological signals from within. A collection of M. xanthus cells behaves, in many respects, like a multicellular organism. For these reasons M. xanthus offers unparalleled access to a regulatory network that controls development and that organizes cell movement on surfaces. The genome of M. xanthus is large (9.14 Mb), considerably larger than the other sequenced delta-proteobacteria. We suggest that gene duplication and divergence were major contributors to genomic expansion from its progenitor. More than 1,500 duplications specific to the myxobacterial lineage were identified, representing >15% of the total genes. Genes were not duplicated at random; rather, genes for cell-cell signaling, small molecule sensing, and integrative transcription control were amplified selectively. Families of genes encoding the production of secondary metabolites are overrepresented in the genome but may have been received by horizontal gene transfer and are likely to be important for predation.

Deltaproteobacteria↗

Complete genome sequence of Caulobacter crescentus.

The complete genome sequence of Caulobacter crescentus was determined to be 4,016,942 base pairs in a single circular chromosome encoding 3,767 genes. This organism, which grows in a dilute aquatic environment, coordinates the cell division cycle and multiple cell differentiation events. With the annotated genome sequence, a full description of the genetic network that controls bacterial differentiation, cell growth, and cell cycle progression is within reach. Two-component signal transduction proteins are known to play a significant role in cell cycle progression. Genome analysis revealed that the C. crescentus genome encodes a significantly higher number of these signaling proteins (105) than any bacterial genome sequenced thus far. Another regulatory mechanism involved in cell cycle progression is DNA methylation. The occurrence of the recognition sequence for an essential DNA methylating enzyme that is required for cell cycle regulation is severely limited and shows a bias to intergenic regions. The genome contains multiple clusters of genes encoding proteins essential for survival in a nutrient poor habitat. Included are those involved in chemotaxis, outer membrane channel function, degradation of aromatic ring compounds, and the breakdown of plant-derived carbon sources, in addition to many extracytoplasmic function sigma factors, providing the organism with the ability to respond to a wide range of environmental fluctuations. C. crescentus is, to our knowledge, the first free-living alpha-class proteobacterium to be sequenced and will serve as a foundation for exploring the biology of this group of bacteria, which includes the obligate endosymbiont and human pathogen Rickettsia prowazekii, the plant pathogen Agrobacterium tumefaciens, and the bovine and human pathogen Brucella abortus.

Adaptation, Biological↗

Genome sequences of Chlamydia trachomatis MoPn and Chlamydia pneumoniae AR39.

The genome sequences of Chlamydia trachomatis mouse pneumonitis (MoPn) strain Nigg (1 069 412 nt) and Chlamydia pneumoniae strain AR39 (1 229 853 nt) were determined using a random shotgun strategy. The MoPn genome exhibited a general conservation of gene order and content with the previously sequenced C.trachomatis serovar D. Differences between C.trachomatis strains were focused on an approximately 50 kb 'plasticity zone' near the termination origins. In this region MoPn contained three copies of a novel gene encoding a >3000 amino acid toxin homologous to a predicted toxin from Escherichia coli O157:H7 but had apparently lost the tryptophan biosyntheis genes found in serovar D in this region. The C. pneumoniae AR39 chromosome was >99.9% identical to the previously sequenced C.pneumoniae CWL029 genome, however, comparative analysis identified an invertible DNA segment upstream of the uridine kinase gene which was in different orientations in the two genomes. AR39 also contained a novel 4524 nt circular single-stranded (ss)DNA bacteriophage, the first time a virus has been reported infecting C. pneumoniae. Although the chlamydial genomes were highly conserved, there were intriguing differences in key nucleotide salvage pathways: C.pneumoniae has a uridine kinase gene for dUTP production, MoPn has a uracil phosphororibosyl transferase, while C.trachomatis serovar D contains neither gene. Chromosomal comparison revealed that there had been multiple large inversion events since the species divergence of C.trachomatis and C.pneumoniae, apparently oriented around the axis of the origin of replication and the termination region. The striking synteny of the Chlamydia genomes and prevalence of tandemly duplicated genes are evidence of minimal chromosome rearrangement and foreign gene uptake, presumably owing to the ecological isolation of the obligate intracellular parasites. In the absence of genetic analysis, comparative genomics will continue to provide insight into the virulence mechanisms of these important human pathogens.

Animals↗

Predictors of course in obsessive-compulsive disorder.

Systematic studies of course of illness in obsessive-compulsive disorder (OCD) using standardized diagnostic criteria are relatively rare. In the present study, 100 patients diagnosed with OCD were prospectively followed for up to 5 years. Other comorbid conditions included anxiety disorders (76%), major depressive disorder (33%), and at least one personality disorder (33%), mainly in the anxious cluster. Approximately 20% of patients had full remission and 50% had partial remission during follow-up. Significant predictors of partial remission included being married and having lower global severity scores at intake; the presence of major depression was marginally predictive of poorer course. Adequate serotonergic medication was associated with worse course, but findings are likely spurious. Only marital status and global severity were retained as predictors in a final regression model. Findings are discussed with regard to sample characteristics and similarity to other reports on predictors of course and of treatment outcome.

Adult↗

Does the use of topical lidocaine, epinephrine, and tetracaine solution provide sufficient anesthesia for laceration repair?

OBJECTIVE: To determine: 1) the effectiveness of lidocaine, epinephrine, and tetracaine (LET) solution in eliminating or reducing the pain experienced in suturing superficial lacerations in adult patients; and 2) the effectiveness of LET in reducing the pain of local anesthetic injection. METHODS: A prospective, randomized, double-blind study in which 60 adult patients with superficial lacerations were entered was conducted in the ED of a community-based teaching hospital affiliated with the University of Toronto. Following application of the LET or placebo (sterile water) solution to the laceration, a visual analog pain scale was recorded by the patient upon needle probing of the wound margin. If probing was painless, the laceration was repaired using LET alone. If injection of local anesthetic was required, an additional pain scale was elicited to quantify the attenuation of the pain of injection by the prior application of LET. RESULTS: Pain scale values on needle probing were significantly reduced in the LET group vs the placebo group (medians of 4.0 vs 5.0 cm, respectively; p < 0.05). Only 13 of the 30 patients in the LET group required additional anesthetic, while all 30 patients in the placebo group requested local anesthetic. Pain scale values on injection of local anesthetic were not significantly different between the LET and placebo groups (medians of 3.5 vs 5.0 cm, respectively; p = 0.09), although there was a trend for lower pain scale values for those patients who received LET. No adverse effects were noted after the application of either LET or placebo solution. Follow-up was achieved for 54 of 60 patients with only 1 complication (a wound infection) reported in the LET group. CONCLUSIONS: Significantly fewer patients require an injectable anesthetic when LET is applied. Those who do require an injection may experience less discomfort. These advantages should be balanced against the 20 to 30 minutes necessary for the LET to take effect.

Adult↗

Benzene inhibition of in vitro rabbit reticulocyte haem synthesis at delta aminolaevulinic acid synthetase: reversal of benzene toxicity by pyridoxine.

Benzene (0.113 M) inhibited haem and protein synthesis in rabbit reticulocytes. This inhibition of haem synthesis was found when L-2-[14C]-glycine was used as the radioactive precursor. However, when 4-[14C]delta-aminolaevulinic acid (ALA) was used, there was no significant inhibition. Since ALA measures the haem synthetic pathway beyond the enzyme delta-aminolaevulinic acid synthetase (ALA synthetase), these results suggest that benzene inhibits haem synthesis at or before ALA synthetase. This was confirmed by demonstrating that 1 mM ALA both protected against and reversed the benzene inhibition of reticulocyte protein synthesis. In addition, 1 mM pyridoxine both protected against and reversed the benzene inhibition of reticulocyte protein synthesis. In addition, ImM pyridoxine both protected against and reversed the benzene inhibition of reticulocyte haem and protein synthesis. These results indicate that benzene (or a metabolite) either competes with pyridoxal phosphate at ALA synthetase or competes with pyridoxine for pyridoxal phosphokinase. These results are discussed in terms of their implications for the possible roles of ALA synthetase and the haemin-controlled repressor in benzene-induced aplastic anaemia.

5-Aminolevulinate Synthetase↗

Course of social functioning after remission from panic disorder.

While symptom status and social functioning have been observed to be correlated in many cross-sectional studies, little is known about the time course of change in functioning after a change in diagnostic status. Using data from a large longitudinal study of anxiety disorders, we present analyses of the time course of seven domains of social functioning up to 18 months before and after remission from panic disorder with or without agoraphobia. The effect of remission from panic disorder varies by domain. Four domains show a change in outcome, usually positive, after remission. The presence of major depressive disorder (MDD) affects the course of functioning for two domains. Generalized anxiety disorder (GAD) was observed to have effects on five of seven domains. For some domains there is improvement at approximately the same time as change in diagnostic status, although progressive change was seen in others. The amount of improvement was modest on average, indicating that other factors beyond panic symptoms may limit post-remission improvement in social functioning.

Major Depressive Disorder↗

MR fat suppression technique in the evaluation of normal structures of the knee.

The chopper fat suppression (CFS) pulse sequence, which is a phase sensitive implementation of the Dixon fat suppression method and the spin echo (SE) pulse sequence, was used in the evaluation of anatomic structures of the normal knee using 48 sets of imaging sequences in six volunteers using a repetition time/echo time combination of 1,500/30, 60 ms. A demonstration of the CFS technique in 10 patients with suspected knee pathology is also presented. A semiquantitative grading scale was established to rate anatomic visualization and used to compare CFS and SE pulse sequence techniques. The results in normal subjects demonstrate that hyaline cartilage is significantly better visualized by fat suppression pulse sequence than by conventional SE pulse sequence in the coronal and sagittal planes of imaging (p less than 0.001). The preliminary results from patients studies suggest that CFS imaging may be useful in the evaluation of meniscal tears, in the differentiation of hyaline cartilage from joint fluid, and in the detection of both soft tissue and bone injuries.

Adipose Tissue↗

The relationship of interleukin-1 and immune functions to sleep in humans.

Serial sampling of peripheral blood from six healthy adult male volunteers was performed during daytime waking and nighttime sleeping. In addition, sleep physiology was assessed in all subjects (Ss) and sleep stages scored blind by standard criteria. Samples of plasma were analyzed for cortisol (Co) levels, functional interleukin-1 (IL-1), and interleukin-2 (IL-2) activity. Peripheral blood monocytes (PBM) were assayed to evaluate natural killer (NK) activity and mitogen responsiveness. Dramatic increase in IL-1 activity along with changes in other immune functions occurred during sleep and were related to onset of slow wave sleep.

Adult↗

Comparative genomics and understanding of microbial biology.

The sequences of close to 30 microbial genomes have been completed during the past 5 years, and the sequences of more than 100 genomes should be completed in the next 2 to 4 years. Soon, completed microbial genome sequences will represent a collection of >200,000 predicted coding sequences. While analysis of a single genome provides tremendous biological insights on any given organism, comparative analysis of multiple genomes provides substantially more information on the physiology and evolution of microbial species and expands our ability to better assign putative function to predicted coding sequences.

Bacteria↗