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Biomedical subjects

Margaret Rennels

Publications and source records attributed to Margaret Rennels.

7 recordsLinked to original sources
PubMed2006

Analysis of reversions in the 5'-untranslated region of attenuated poliovirus after sequential administration of inactivated and oral poliovirus vaccines.

Replication of Sabin strains used in oral poliovirus vaccine (OPV) in the intestines of vaccine recipients leads to reversions that increase virus neurovirulence. Previously, a small study reported that prior immunization with inactivated poliovirus vaccine (IPV) resulted in faster accumulation of revertant virus, thus potentially increasing the risk of vaccine-associated paralytic poliomyelitis. We studied the impact that prior immunization with IPV and OPV has on shedding of revertant virus by healthy infants. By polymerase chain reaction (PCR), we amplified full-length poliovirus genomes directly from stool specimens from unimmunized infants and from infants previously immunized with IPV or OPV. The amplicons were used to quantify reversions in the 5'-untranslated region, using oligonucleotide microarray hybridization. Nearly all 140 samples that were PCR positive contained varying amounts of revertants of all 3 poliovirus serotypes. Polioviruses of Sabin types 2 and 3 reverted more easily than those of type 1. Prior vaccination with IPV did not increase the proportion of revertants after OPV administration.

DNA, Viral↗
PubMed2005

Effect of different vaccination schedules on excretion of oral poliovirus vaccine strains.

Inactivated poliovirus vaccine (IPV) is believed to induce significantly lower mucosal immunity than oral poliovirus vaccine (OPV). Most of the data supporting this were generated before enhanced IPV (eIPV) was introduced. Excretion of poliovirus by OPV recipients can be used to assess intestinal immunity. We studied polymerase chain reaction amplification of viral complementary DNA from the stool of children vaccinated with either OPV alone or eIPV. Of first-time OPV recipients, 92% excreted virus after 1 week, and 81% excreted virus after 3 weeks. Prior vaccination with OPV reduced the number to 22% and shortened the duration of virus excretion (to 5% after 3 weeks). Two doses of IPV reduced the number of poliovirus-positive 1-week samples (to 76%), the duration of shedding (to 37% at 3 weeks), and the quantity of excreted virus. This suggests that IPV-vaccinated communities are partially protected from the spread of poliovirus. Further enhancement of IPV potency may lead to even higher levels of mucosal immunity.

DNA, Complementary↗
PubMed2004

An array microscope for ultrarapid virtual slide processing and telepathology. Design, fabrication, and validation study.

This paper describes the design and fabrication of a novel array microscope for the first ultrarapid virtual slide processor (DMetrix DX-40 digital slide scanner). The array microscope optics consists of a stack of three 80-element 10 x 8-lenslet arrays, constituting a "lenslet array ensemble." The lenslet array ensemble is positioned over a glass slide. Uniquely shaped lenses in each of the lenslet arrays, arranged perpendicular to the glass slide constitute a single "miniaturized microscope." A high-pixel-density image sensor is attached to the top of the lenslet array ensemble. In operation, the lenslet array ensemble is transported by a motorized mechanism relative to the long axis of a glass slide. Each of the 80 miniaturized microscopes has a lateral field of view of 250 microns. The microscopes of each row of the array are offset from the microscopes in other rows. Scanning a glass slide with the array microscope produces seamless two-dimensional image data of the entire slide, that is, a virtual slide. The optical system has a numerical aperture of N.A.= 0.65, scans slides at a rate of 3 mm per second, and accrues up to 3,000 images per second from each of the 80 miniaturized microscopes. In the ultrarapid virtual slide processing cycle, the time for image acquisition takes 58 seconds for a 2.25 cm2 tissue section. An automatic slide loader enables the scanner to process up to 40 slides per hour without operator intervention. Slide scanning and image processing are done concurrently so that post-scan processing is eliminated. A virtual slide can be viewed over the Internet immediately after the scanning is complete. A validation study compared the diagnostic accuracy of pathologist case readers using array microscopy (with images viewed as virtual slides) and conventional light microscopy. Four senior pathologists diagnosed 30 breast surgical pathology cases each using both imaging modes, but on separate occasions. Of 120 case reads by array microscopy, there were 3 incorrect diagnoses, all of which were made on difficult cases with equivocal diagnoses by light microscopy. There was a strong correlation between array microscopy vs. "truth" diagnoses based on surgical pathology reports. The kappa statistic for the array microscopy vs. truth was 0.96, which is highly significant (z=10.33, p <0.001). There was no statistically significant difference between rates of agreement with truth between array microscopy and light microscopy (z=0.134, p >0.05). Array microscopy and light microscopy did not differ significantly with respect to the number/percent of correct decisions rendered (t=0.552, p=0.6376) or equivocal decisions rendered (t=2.449, p=0.0917). Pathologists rated 95.8% of array microscopy virtual slide images as good or excellent. None were rated as poor. The mean viewing time for a DMetrix virtual slide was 1.16 minutes. The DMetrix virtual slide processor has been found to reduce the virtual slide processing cycle more than 10 fold, as compared with other virtual slide systems reported to date. The virtual slide images are of high quality and suitable for diagnostic pathology, second opinions, expert opinions, clinical trials, education, and research.

Equipment Design↗
PubMed2004

Dosage escalation, safety and immunogenicity study of four dosages of a tetravalent meninogococcal polysaccharide diphtheria toxoid conjugate vaccine in infants.

BACKGROUND: Young children have the highest incidence of meningococcal infection. Approximately 50% of disease in United States children less than 2 years of age is caused by serogroups C and Y. In the developing world, serogroups A and W-135 cause outbreaks and epidemics of infection. METHODS: Three groups of 30 infants were enrolled. The first group of infants was given 3 doses of a quadrivalent (group A, C, Y, W-135) polysaccharide meningococcal vaccine conjugated to diphtheria toxoid (MCV-4) at a dosage of 1 microg of each serogroup polysaccharide. The second group of infants was given MCV-4 at a dosage of 4 microg, and the last group of children received a 10-microg dosage. Vaccinations were given at 2, 4 and 6 months of age.A subset of these children was vaccinated at 15 to 18 months of age with licensed meningococcal polysaccharide (A, C, Y, W-135) vaccine. Serum bactericidal antibody (SBA) titers were measured with baby rabbit complement. RESULTS: The proportion of infants with local reactions increased significantly with increasing dosages after Injection 1 and 3. Approximately 1 month after completion of the primary series, the proportion of infants with an SBA titer > or = 1/8 ranged from 54 to 92%, depending on the serogroup and dose of polysaccharide contained in the vaccine. The SBA geometric mean titer varied from 17.4 to 101.6. There was no statistically significant difference between the SBA responses among the 3 dosage groups. After vaccination with polysaccharide vaccine at 15 to 18 months of age, mean fold increases in SBA of 4.9 to 170.3 were observed, suggesting an anamnestic response. CONCLUSIONS: MCV-4 appears to have a reactogenicity profile acceptable to parents and health care providers. It was only modestly immunogenic in infants, but it appeared to prime the immune system of the majority of infants given three doses in infancy. There is no statistically significant immunologic advantage conferred by increasing the dosage beyond 4 microg/ml, and local reactions are more frequent after the 10-microg/ml dosage.

Antibodies, Bacterial↗
PubMed2003

FOXC2 haploinsufficient mice are a model for human autosomal dominant lymphedema-distichiasis syndrome.

Lymphedema-distichiasis (LD) (OMIM 153400) is a rare autosomal-dominant condition characterized by pubertal onset of lower limb lymphedema and an aberrant second row of eyelashes arising from the meibomian glands. In some patients cardiac, skeletal and other defects coexist. We previously identified inactivating, nonsense and frameshift mutations in the forkhead transcription factor FOXC2 in affected members of LD families. To further delineate the relationship of FOXC2 deficiency to the clinical (and lymphangiodysplastic) phenotype in this syndrome, we performed dynamic lymphatic imaging and immunohistochemical examination of lymphatic tissues in mice heterozygous (+/-) for a targeted disruption of Foxc2. Adult heterozygote mice characteristically exhibited a generalized lymphatic vessel and lymph node hyper plasia and rarely exhibited hindlimb swelling. Retrograde lymph flow through apparently incompetent interlymphangion valves into the mesenteric nodes, intestinal wall and liver was also observed. In addition, Foxc2 +/- mice uniformly displayed distichiasis. We conclude that Foxc2 haploinsufficient mice mimic closely the distinctive lymphatic and ocular phenotype of LD patients. Furthermore, the craniofacial, cardiovascular and skeletal abnormalities sometimes associated with LD have previously been shown to be fully penetrant in homozygous Foxc2 null mice. This Foxc2 mutant mouse thus provides an ideal model for exploring molecular mechanisms and physiologic events in mesenchymal differentiation associated with lymphatic growth and development and the clinical abnormalities seen in human LD syndrome.

Animals↗