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Biomedical subjects

M Kenna

Publications and source records attributed to M Kenna.

13 recordsLinked to original sources

Intraneuronal ApoE in human visual cortical areas reflects the staging of Alzheimer disease pathology.

Alzheimer disease (AD) is marked by progressive loss of cortical neurons with associated cognitive decline. Multiple genetic and environmental factors likely contribute to this progressive loss. Such genetic factors include the polymorphic locus (APOE) that encodes apolipoprotein E (apoE). In order to investigate a possible correspondence between cellular localization of apoE and the neuropathology of AD, we examined the distribution of apoE-immunoreactive neurons in visual cortical areas with different apparent susceptibility to AD neuropathology (areas 17-primary sensory, 18-secondary sensory, and inferior temporal-association cortex) at different stages of AD pathology as described by Braak and Braak. We found that intraneuronal apoE was present at all these stages, however, only in visual cortical regions known to be vulnerable to AD. In the late stages, the laminar distribution of apoE-immunoreactivity matched the distribution of other markers of AD pathology, especially modified tau. These data support previous findings that intraneuronal apoE in neocortex is common in aged, nondemented controls and demonstrate that it may be more common in regions at risk for AD pathology. Thus, intraneuronal accumulation of apoE may be an attribute of cortical neurons that are more vulnerable to age-related injury with the presence of apoE antedating the classical indices of late-onset AD pathology.

Aged↗

Cochlear implantation in children.

Cochlear implantation in the pediatric population is no longer considered experimental practice since the Food and Drug Administration (FDA) approved the Nucleus 22 Channel cochlear implant in 1990. Today, cochlear implantation is a viable option for selected children with profound hearing loss to achieve potential language development. Not every child is a candidate, however, nor can implantation rectify the underlying cause of deafness or restore normal hearing function. For successful outcomes in proper candidates, rigorous pre-surgical evaluation and screening followed by long-term rehabilitation and education are necessary for both child and family. The close collaboration of an interdisciplinary team is essential throughout the process.

Adolescent↗

An essential yeast gene with homology to the exonuclease-encoding XRN1/KEM1 gene also encodes a protein with exoribonuclease activity.

An essential gene, designated HKE1/RAT1, has been isolated from the yeast Saccharomyces cerevisiae and characterized. The gene encodes a protein of 116 kDa (p116) and has significant homology to another yeast gene (XRN1/KEM1) encoding a related protein (p175) with 5'-->3' exonuclease activity as well as activities involving chromosomal DNA pairing and mechanics. Preliminary analysis of an hke1ts mutant reveals a precipitous decline in the translation of mRNA at the nonpermissive temperature. Sporulation of heterozygous HKE1/hke1::URA3 diploids reveals that this gene, unlike the highly related XRN1/KEM1 gene, is essential for cell viability. Overexpression of the homologous gene product, p175, failed to rescue cells lacking a functional p116. In vitro studies demonstrate that p116 is a protein with 5'-->3' exoribonuclease activity, a major activity of the related p175. An immunoreactive RNase activity of 116 kDa is abolished with antiserum against p116. Both the level of this protein and the RNase activity correlate with HKE1 gene dosage. The RNase activity purifies coincidentally with a previously described 116-kDa RNase having 5'-->3' exoribonuclease activity.

Cloning, Molecular↗

The structure of a primitive kinetochore.

The isolation of yeast centromeres has provided the opportunity to describe the molecular structure of chromosome attachments to the mitotic spindle. Nucleolytic probes of chromatin structure and construction of conditional mutants in centromere function have been used to study the regulation and assembly of centromeres throughout the cell cycle in Saccharomyces cerevisiae.

Base Sequence↗

Cis- and trans-acting factors affecting the structure of yeast centromeres.

The isolation of yeast centromeres has provided the opportunity to describe the molecular structure of chromosome attachments to the mitotic spindle. Nucleolytic probes of chromatin structure and analysis of genetically altered centromeres have been used to determine the primary sequence and positional requirements for assembly of this chromosomal domain into a functional unit. Structural analysis of the centromere in wild-type and mutant strains provides the first indication of specific proteins associated with centromere DNA in vivo.

Centromere↗

Selective excision of the centromere chromatin complex from Saccharomyces cerevisiae.

We have taken advantage of the known structural parameters associated with centromere DNA in vivo to construct a CEN fragment that can be selectively excised from the chromatin DNA with restriction endonucleases. CEN3 DNA is organized in chromatin such that a 220-250-bp region encompassing the elements of centromere homology is resistant to nuclease digestion. Restriction enzyme linkers encoding the Bam HI-recognition site were ligated to a 289 base pair DNA segment that spans the 220-250-bp protected core (Bloom et al., 1984). Replacement of this CEN3-Bam HI linker cassette into a chromosome or plasmid results in formation of a complete structural and functional centromeric unit. A centromere core complex that retains its protected chromatin conformation can be selectively excised from intact nuclei by restriction with the enzyme Bam HI. The centromeric protein-DNA complex is therefore not dependent upon the intact torsional constrains on linear chromosomes for its structural integrity. Isolation of this complex provides a novel approach to characterizing authentic centromeric proteins bound to DNA in their native state.

Cell Nucleus↗

Amplification and elevated expression of c-myc in a chemically induced mouse colon tumor.

The amplification and level of expression of four cellular oncogenes was investigated in dimethylhydrazine-induced Mouse Colon Tumor 36 of Corbett et al. [Corbett, T. H. Griswold, D. P., Jr., Roberts, B. J., Peckham, J. C., and Schabel, F. M., Jr. Cancer (Phila.), 40:2660-2680, 1977], which has been used to evaluate potential chemotherapeutic agents. A 30- to 40-fold amplification of c-myc was observed in the tumor DNA as compared to the DNA of normal colonic mucosa and liver. No changes were observed in the number of copies of c-mos, erbB, or bas. Digestion with three different restriction enzymes demonstrated that there was no major alteration in the genomic structure of c-myc in the amplified DNA. The level of c-myc RNA was 10-fold higher in both the total and polyadenylated RNA from the tumor when compared to RNA from normal colonic mucosa. Probes specific for the three myc exons were used in hybridization experiments and demonstrated that all three exons were present in the amplified DNA and in the mRNA.

Animals↗

Cochlear implants and the deaf child: a nursing perspective.

Cochlear implants are no longer considered new or experimental technology and are available for children with profound sensorineural hearing loss. Pediatric cochlear implantation requires a multidisciplinary team approach with contributions from surgeons, audiologists, speech-language pathologists, psychologists, nurses, special educators, and parents. The decision to perform cochlear implantation in children must be seriously considered. Some in the deaf community voice strong objections to the procedure. Additionally, it requires an enormous commitment on the part of the family and the health care system in both personal and financial terms. The surgery has some risks, and the rehabilitation period is lengthy. Outcomes are variable, and many factors play a role in a child's successful use of implants. Nonetheless, gradual, steady improvement in speech perception, speech production, and language typically occurs. The approach of Children's Hospital in Boston to the assessment, the surgical procedure, and follow-up is detailed here.

Adolescent↗