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Biomedical subjects

P Erickson

Publications and source records attributed to P Erickson.

At least 19 recordsLinked to original sources

Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt.

We have developed a restriction map of the chromosome 21 breakpoint region involved in t(8;21)(q22;q22.3) acute myelogenous leukemia (AML) and have isolated a genomic junction clone containing chromosome 8 and 21 material. Using probes from these regions, rearrangements have been identified in each of nine cases of t(8;21) AML examined. In addition, we have isolated cDNA clones from a t(8;21) AML cDNA library that contain fused sequences from chromosome 8 and 21. The chromosome 8 component, referred to as ETO (for eight twenty-one), is encoded over a large genomic region, as suggested by the analysis of corresponding yeast artificial chromosomes (YACs). The DNA sequence of the chromosome 21 portion of the fusion transcript is derived from the normal AML1 gene. A striking similarity (67% identity over 387 bp, with a corresponding 69% amino acid identity) was detected between AML1 and the Drosophila segmentation gene, runt. The critical consequence of the translocation is the juxtaposition of 5' sequences of AML1 to 3' sequences of ETO, oriented telomere to centromere on the der(8) chromosome.

Amino Acid Sequence

Characterization of the submicroscopic deletion in the small-cell lung carcinoma (SCLC) cell line U2020.

The small-cell lung carcinoma cell line U2020 contains a submicroscopic, homozygous deletion that removes a chromosomal segment within 3p13-p14, including the locus D3S3. We have sublocalized 49 additional probes to the 3p13-p14.2 region and have identified 7 new DNA markers that arise from within the U2020 deletion. The estimated size of the deletion, based on marker density, is approximately 4-5 megabases (Mb). Including D3S3, 7 of the 8 markers have been linked by pulsed-field gel (PFG) electrophoresis over an area of approximately 2 Mb. Including the one unlinked marker, PFG analysis accounts for about 3 Mb of the region. The U2020 deletion appears confined to the 3p13-p14.2 region and does not include the candidate tumor suppressor gene, protein-tyrosine phosphatase gamma (PTPG).

Carcinoma, Small Cell

Role of visual acuity, stereoacuity, and ocular dominance in monovision patient success.

Monovision (MV) contact lens correction of presbyopia induces substantial reductions in stereoacuity and small reductions in binocular visual acuity (VA). This study examined those effects in a group of successful and a group of unsuccessful MV patients. Compared to performance with a full binocular correction, the unsuccessful group demonstrated significant losses in both functions. These reductions were smaller in the successful group and of marginal statistical significance only for stereoacuity. Laterality of sighting dominance and laterality of distance/near correction had minimal effect on the results.

Adult

Isolation of a yeast artificial chromosome spanning the 8;21 translocation breakpoint t(8;21)(q22;q22.3) in acute myelogenous leukemia.

The 8;21 translocation is one of the most common specific rearrangements in acute myelogenous leukemia. We have identified markers (D21S65 and a Not I boundary clone, Not-42, referred to as probe B) flanking the chromosome 21 translocation breakpoint (21q22.3) that demonstrate physical linkage in normal genomic DNA, by using at least three restriction endonucleases (Not I, Sac II, and BssHII), and that are located not more than 250-280 kilobases apart. Pulsed-field gel analysis of DNA from somatic cell hybrids containing the 8;21 translocation chromosomes demonstrates rearrangement of these markers. A 470-kilobase yeast artificial chromosome, YAC-Not-42, has been isolated that contains both probes. Mapping of lambda subclones constructed from YAC-Not-42 suggests that greater than 95% (25/26 probes tested) of the yeast artificial chromosome DNA is located on the proximal (D21S65) side of the breakpoint. In situ hybridization studies using metaphase chromosomes from five acute myelogenous leukemia patients with the 8;21 translocation confirmed these results and demonstrated the translocation of probe B to the derivative chromosome 8. A chromosome walk of approximately 39 kilobases from probe B has allowed identification of the breakpoint in DNA from a somatic cell hybrid containing the derivative chromosome 8. Since probe B contains conserved DNA sequences and is in close proximity to the translocation breakpoint, it may represent a portion of the involved gene on chromosome 21.

Blotting, Southern

A 2.5-Mb physical map within 3p21.1 spans the breakpoint associated with Greig cephalopolysyndactyly syndrome.

Numerous investigations suggest that one or more genes residing in the p14 to p21 region of human chromosome 3 are critical to the development of neoplastic diseases such as renal cell carcinoma and small-cell lung cancer (SCLC). This region is additionally involved in several interchromosomal translocations, one of which is associated with the developmental disorder Greig cephalopolysyndactyly syndrome. A series of five loci that map in close proximity to the Greig syndrome breakpoint [t(3;7)(p21.1;p13)] at 3p21.1 have been physically linked by pulsed-field gel analysis over a 2.5-Mb region. The probes include ACY1, cA84 (D3S92), cA199 (D3S93), pHF12-32 (D3S2), and MW-Not153 (D3S332). The Greig 3;7 translocation breakpoint was discovered between clones cA199 and MW-Not153, separated by 825 kb. Further analysis revealed comigration of a rearranged fragment detected by MW-Not153 and a chromosome 7 probe previously shown to be in close proximity to the breakpoint (CRI-R944). This latter probe also detects a rearrangement in a second Greig-associated translocation, (6;7)(q27;p13). The physical map resulting from this analysis orders the markers along the chromosome and identifies several locations for CpG islands, likely associated with genes. Although probe pEFD145.1 (D3S32) has been genetically linked to D3S2 (2 cM), physical linkage to the other five loci could not be demonstrated. One of the linked loci, D3S2, has been widely utilized in the analysis of chromosome 3p loss in several malignant diseases. Since expression of ACY1, a housekeeping gene, is specifically reduced in many cases of SCLC, knowledge of its precise chromosomal position and identification of neighboring putative gene loci should facilitate investigation into the mechanism of this reduction.

Cell Line

Isolation and regional mapping of NotI and EagI clones from human chromosome 21.

NotI and EagI boundary libraries were constructed for human chromosome 21. One hundred forty-seven clones were isolated from the somatic cell hybrid 72532X-6 and localized using a hybrid mapping panel. After identification of those clones, which were isolated more than once, as well as those probes derived from a previously unrecognized integrated non-chromosome-21 fragment, 58 individual boundary clones (plus 2 additional NotI-EcoRI clones isolated from a flow-sorted library) were localized to 11 separate regions. The distribution of these probes is highly nonrandom, with 50% of the clones located in the distal band 21q22.3. Two probes, Not50 and Eag101, map to regions in the very proximal long arm which may contain the gene responsible for familial Alzheimer's disease (AD1), and Not50 would appear to be more proximal than D21S16 (E9). Twenty-eight probes map to the region between superoxide dismutase (SOD1) and the ETS2 oncogene, which appears to contain genes responsible for many of the phenotypic features of Down syndrome. Twenty clones contain (GT)n repeats, as determined by hybridization to a CA polymer, and should provide additional highly polymorphic probes. Closure of gaps in the physical linkage map of chromosome 21 should be facilitated by the isolation of these probes, as they identify many of the unmethylated CpG-rich islands that have hindered pulsed-field gel analysis. They will also be useful in identifying a set of genes in proximity to NotI and EagI restriction sites, as well as conserved DNA sequences for comparative mapping studies.

Animals

Sighting dominance and monovision distance binocular fusional ranges.

Clinicians typically apply the distance correction to the dominant sighting eye in fitting presbyopic patients with monovision (MV) contact lenses. We evaluated the effect of this fitting strategy on distance binocular fusional ranges for 23 presbyopic subjects. This sample was composed of successful and unsuccessful MV wearers. Fusional ranges for the two MV fitting possibilities (distance lens on the dominant eye, near lens on the dominant eye) were compared to fusional ranges in which both eyes were fitted with the distance correction. A greater esophoric shift and greater reduction in vergence ranges were demonstrated when the non-dominant eye received the clear image compared to when the dominant eye received the clear image. Successful MV patients demonstrated these effects to a lesser degree than did unsuccessful patients. In general, effects of MV on distance binocular fusional ranges were fewer when successful MV subjects received the clear image in the dominant eye.

Contact Lenses

The effect of monovision lenses on the near-point range of single binocular vision.

Monovision (MV) contact lenses are commonly used to provide optical correction for presbyopia. Based on their review of the literature on fusional mechanisms, Erickson and Schor predicted that monocular blur associated with MV should not be sufficient to disrupt binocular fusion. We found that fusional vergence ranges in presbyopes corrected with MV were not substantially different from those measured under full binocular nearpoint correction. There were small but statistically significant tendencies for the phoria and base-in vergences to be less exo under MV conditions. Comparisons of findings between a group of successfully adapted MV patients and a group of patients who were unsuccessful with MV indicated no significant differences, suggesting that there is no adaptation effect for these performance variables and that these tests are not effective predictors of MV success.

Adaptation, Ocular

Development of a somatic cell hybrid mapping panel and molecular probes for human chromosome 3.

A somatic cell hybrid mapping panel and molecular probes have been developed for human chromosome 3. This panel defines 11 regions for the short and long arms of the chromosome. Four hundred thirty-two probes have been mapped using these hybrids. One hundred thirty-one of these probes were derived from EcoRI and HindIII flow-sorted libraries. The remaining 301 probes were isolated from NotI boundary and random (partial MboI) libraries constructed from a hybrid that provided a relative enrichment in 3p DNA sequences. For some regions of the chromosome, significant differences in the distribution of probes were noted. This was observed for both the unique sequence flow-sorted and NotI probes. These differences are in agreement with previous suggestions that Giemsa light bands are GC-rich, and therefore gene-rich (especially housekeeping genes), and that the Giemsa dark bands may contain DNA that is more highly condensed. The isolation of probes from different types of libraries, or by different screening strategies, appears to reduce deficiencies that might arise from the use of probes derived with a more limited approach. These hybrids and probes should facilitate the construction of physical and genetic linkage maps to identify various disease loci involving chromosome 3.

Animals

Effects of intraocular lens position errors on postoperative refractive error.

Previous theoretical attempts to predict the refractive effects of intraocular lens (IOL) misalignment have resulted in conflicting information. Discrepancies in both the potential magnitude and direction of the refractive changes exist in the literature. This paper provides a detailed description of the mathematical framework required to achieve a valid predictive model and a quantitative analysis of the effects of IOL positional errors. The effects of misalignment are shown to influence the spherical refractive component primarily. Astigmatism related to oblique incidence is generally small. Movement of the IOL away from the retina produces myopia, while movement toward the retina produces hyperopia. It is likely that longitudinal IOL positional errors are a principal component of postoperative refractive errors. Alignment errors, on the other hand, must have generally minor effects on refraction.

Astigmatism

Visual function with presbyopic contact lens correction.

All forms of ophthalmic correction for presbyopia require compromises in viewing flexibility and visual function. The unique effects on vision of contact lenses used in managing presbyopia are especially intriguing and potentially problematic. Bifocal contact lenses produce unique changes in the nature and quality of the retinal image. In monovision (MV) correction, anisometropia is intentionally created by fitting one eye to see clearly at optical infinity and the other eye to see clearly at the near working distance. Our review of the literature indicates that most visual functions are affected by these departures from the conventional optical correction strategies used on nonpresbyopes. Sensory functions such as contrast sensitivity and stereoacuity are affected most, whereas motor functions such as convergence and accommodation are not noticeably impaired. MV appears to produce a more widely acceptable visual compromise than currently available bifocal contact lenses for most patients.

Adaptation, Ocular

Monovision.

Monovision has been a controversial contact lens correction modality for over 30 years. This paper addresses the major issues and concerns and considers them in the light of patient safety, visual efficiency and practitioner liability.

Adaptation, Ocular

A new macula lens.

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Equipment Design

Regional and physical mapping studies characterizing the Greig polysyndactyly 3;7 chromosome translocation, t(3;7)(p21.1;p13).

The Greig polysyndactyly-craniofacial anomalies syndrome is an autosomal dominant disorder involving a gene(s) located in band 7p13. We have isolated and characterized a reciprocal 3;7 chromosome translocation that resulted in the syndrome. We have identified two closely linked (0 cM) conserved DNA sequences (P137/p944B) that flank the translocation breakpoint. A pulsed-filed analysis combined with available genetic linkage information demonstrates that the disorder is linked (2 cM) to the T-gamma receptor locus, lending considerable support to the hypothesis that the mouse mutant extra-toes is the counterpart of the Greig syndrome. We have found no evidence that physically links the EGF receptor to the P137/p944B region, again compatible with mouse linkage relationships. The isolation of the der(3) chromosome from the 3;7 translocation has allowed us to regionally localize probes within the 3p21.1 band. For three probes commonly used in heterozygosity experiments with human cancers involving chromosome 3, we have determined that the order from centromere to telomere is D3S3, D3S2, and DNF15S2. Our pulsed-field studies also demonstrate the utility of band density differences combined with partial digests in evaluating linkage relationships. The P137/p944B probes should be useful in examining other hereditary disorders with phenotypic similarities to the Greig syndrome.

Animals

Using composite health status measures to assess the nation's health.

Research in progress at the National Center for Health Statistics for evaluating the usefulness of composite measures of health status for assessing the nation's health is described. Three measures suitable for use in the general population, the Health Insurance Experiment-Functional Limitations (HIE-FL), the Health Utility Index (HUI), and the Quality of Well-being (QWB) scale, have been mapped to data collected in the 1980 National Health Interview Survey (NHIS). Analysis using current algorithms for making composite function status measures according to the QWB methods suggests that traditional single indicators of health tend to overestimate the level of health by about 10%. When symptoms and problems are added to the composite function score, the overestimate as measured by the single indicator is at least 50%. The authors are continuing to validate these algorithms, to develop similar ones for the HIE-FL and HUI, and to extend the analysis to data collected in 1977, 1979, and 1984. Current results indicate that to realize fully the benefits of composite measures, well-established, valid, and reliable measures of health-related quality of life should be included as part of the regular NHIS data collection procedures.

Activities of Daily Living

Factors influencing vision with rigid gas permeable alternating bifocals.

This study assessed the fitting and visual performance of a rigid, gas permeable (RGP), monocentric, alternating bifocal. Fourteen presbyopic eyes each wore 24 different lenses consisting of all combinations of 2 diameters, 2 segment heights, 2 prism ballasts, and 3 fitting relations. The influence of parameter selection on visual performance and the usefulness of clinical measurements in predicting visual performance were determined statistically by multivariate logistic regression. Our results showed that prism, segment height, and the fitting relation can influence distance and near visual performance. Lens movement, postblink segment positioning, and return time were the most useful measured predictors of visual performance.

Aged

Nursing is at war!

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Conflict, Psychological

Effects of interocular blur suppression ability on monovision task performance.

Suppression of anisometropic blur induced by monovision contact lenses was examined in 18 presbyopic subjects. Suppression ability was quantified by reducing the contrast of a bright test target, viewed by subjects wearing a monovision correction, until the blurred image was suppressed. Subjective success with monovision was evaluated using a patient survey and no correlation to blur suppression ability was found. Objective success was evaluated in terms of performance at three near work tasks, each requiring a different level of stereoscopic localization. A significant correlation was found between card filing performance (requiring a moderate level of stereopsis) and blur suppression ability. Correcting either the dominant or non-dominant eye for near in the monovision correction did not significantly affect blur suppression ability. There was no evidence for adaptation to monovision in terms of increasing blur suppression ability over time.

Adult