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Biomedical subjects

C Isaac

Publications and source records attributed to C Isaac.

8 recordsLinked to original sources
PubMed2000

Conserved composition of mammalian box H/ACA and box C/D small nucleolar ribonucleoprotein particles and their interaction with the common factor Nopp140.

Small nucleolar ribonucleoprotein particles (snoRNPs) mainly catalyze the modification of rRNA. The two major classes of snoRNPs, box H/ACA and box C/D, function in the pseudouridylation and 2'-O-methylation, respectively, of specific nucleotides. The emerging view based on studies in yeast is that each class of snoRNPs is composed of a unique set of proteins. Here we present a characterization of mammalian snoRNPs. We show that the previously characterized NAP57 is specific for box H/ACA snoRNPs, whereas the newly identified NAP65, the rat homologue of yeast Nop5/58p, is a component of the box C/D class. Using coimmunoprecipitation experiments, we show that the nucleolar and coiled-body protein Nopp140 interacts with both classes of snoRNPs. This interaction is corroborated in vivo by the exclusive depletion of snoRNP proteins from nucleoli in cells transfected with a dominant negative Nopp140 construct. Interestingly, RNA polymerase I transcription is arrested in nucleoli depleted of snoRNPs, raising the possibility of a feedback mechanism between rRNA modification and transcription. Moreover, the Nopp140-snoRNP interaction appears to be conserved in yeast, because depletion of Srp40p, the yeast Nopp140 homologue, in a conditional lethal strain induces the loss of box H/ACA small nucleolar RNAs. We propose that Nopp140 functions as a chaperone of snoRNPs in yeast and vertebrate cells.

Amino Acid Sequence↗
PubMed1998

Nopp140 functions as a molecular link between the nucleolus and the coiled bodies.

Coiled bodies are small nuclear organelles that are highly enriched in small nuclear RNAs, and that have long been thought to be associated with the nucleolus. Here we use mutational analysis, transient transfections, and the yeast two-hybrid system to show that the nucleolar phosphoprotein Nopp140 functions as a molecular link between the two prominent nuclear organelles. Exogenous Nopp140 accumulated in the nucleolus rapidly, but only after a lag phase in coiled bodies, suggesting a pathway between the two organelles. The expression of partial Nopp140 constructs exerted dominant negative effects on the endogenous Nopp140 by chasing it and other antigens that were common to both organelles out of the nucleolus. The alternating positively and negatively charged repeat domain of Nopp140 was required for targeting to both organelles. In addition, partial Nopp140 constructs caused formation of novel structures in the nucleoplasm and, in the case of the conserved carboxy terminus, led to the dispersal of coiled bodies. As a final link, we identified the coiled body-specific protein p80 coilin in a yeast two-hybrid screen with Nopp140. The interaction of the two proteins was confirmed by coimmunoprecipitation. Taken together, Nopp140 appeared to shuttle between the nucleolus and the coiled bodies, and to chaperone the transport of other molecules.

3T3 Cells↗
PubMed1997

Procalcitonin and C-reactive protein levels in neonatal infections.

In order to assess the potential fo procalcitonin measurement in the management of neonatal sepsis, daily variations in serum procalcitonin (measured by an immunoluminometric assay) were evaluated in 94 control and infected newborn infants in comparison to C-reactive protein (measured by an immunonephelometric method). High levels of procalcitonin correlated with bacterial invasion and showed no discrepancies with C-reactive protein. procalcitonin increased (up to 400 micrograms l-1 and returned to the normal range (< 0.1 microgram l-1) more quickly than C-reactive protein, suggesting that procalcitonin may be an early marker of favourable outcome. Another finding is a significant procalcitonin peak on the first day of life in the control group, independent of any infectious stimulus. In conclusion, procalcitonin seems to be an interesting marker of neonatal sepsis but additional investigations are needed to understand better its mechanism of synthesis in order to determine its clinical usefulness.

Bacterial Infections↗
PubMed1988

Multiple sclerosis: a serial study using MRI in relapsing patients.

Prospective monthly magnetic resonance imaging (MRI) studies were done over 6 months in seven relapsing MS patients. MRI and neurologic evaluations were compared for sensitivity in detecting disease activity. Four patients were clinically stable throughout the study. Three patients had five clinical relapses, two localized to the spinal cord and three to the brainstem. Eighteen new and ten enlarging MRI lesions were seen in five patients. Most lesions were less than 10 mm in diameter. All were clinically silent. Two patients developed major enlarging MRI lesions (seen in three slices) which increased in size over 2 months and then gradually became smaller over 2 months, leaving behind small residual areas of abnormality. There were 36 follow-up scans, 17 of which (47%) showed evidence for increasing activity. Thirteen (36%) of the scans had new lesions, most of them being small. This study shows that MRI evidence for disease activity in MS is much more frequent than is clinical evidence.

Adult↗
PubMed1987

Juvenile sex offenders: development and correction.

This paper addresses the developmental nature of sexually abusive behaviors as they apply to juvenile male sexual offenders. Socialization and sexual victimization are discussed. Three case histories elucidate and support the discussion of the development of victim offending. Significant treatment issues of juvenile male sexual offenders center around the sexual assault cycle which provides a framework for sexual offenders to conceptualize and understand the cognitive, behavioral, psychological, and situational factors which have resulted in their offense(s). Although sexual offenders and sexual offenses are each unique, the sexual assault cycle offers a means of addressing essential commonalities in the treatment of juvenile sexual offenders. Sexual offender specific treatment is viewed as essential for decreasing the risk of further sexual offenses, and thus decreasing the incidence of sexual victimization.

Adolescent↗