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Biomedical subjects

R B Mandell

Publications and source records attributed to R B Mandell.

At least 19 recordsLinked to original sources
PubMed1999

Radioisotope concentrator gene therapy using the sodium/iodide symporter gene.

We demonstrate a novel method of concentrating radiation for tumor imaging or killing. The rat sodium/iodide symporter gene (rNIS) was cloned into a retroviral vector for transfer into cancer cells to mimic the iodide uptake of thyroid follicular cells. In vitro iodide transport shows that the symporter functions similarly in rNIS-transduced tumor cells and rat thyroid follicular cells. rNIS-transduced and control nontransduced (NV) human A375 melanoma xenografts established in vivo in athymic nude mice were imaged using a gamma camera after i.p. injections of 123I. The rNIS-transduced human A375 melanoma tumors are visually distinguishable from and accumulate significantly more radionuclides than NV tumors. In vitro clonogenic assays confirm efficacy and clearly show that rNIS-transduced A375 human melanoma, BNL.1 ME murine transformed liver, CT26 murine colon carcinoma, and IGROV human ovarian carcinoma can be selectively killed by the induced accumulation of 131I. Thus, NIS-based gene therapy may have both diagnostic and therapeutic applications for cancer.

Adenocarcinoma↗
PubMed1999

Measurement of post-lens tear thickness.

PURPOSE: A method to measure the tear film beneath a soft contact lens, referred to as post-lens tear thickness (PLTT), would have many applications to contact lens research. In this study a noninvasive technique for measuring the PLTT is presented. METHODS: The feasibility of measuring the tear layer by optical pachometry was first assessed using a model eye. The baseline corneal thickness (B) of both eyes of 21 subjects was measured, etafilcon-A ionic disposable soft contact lenses (58% water) were inserted, and the total thickness (T) of the cornea, contact lens, and PLTT were measured. After the pachometry readings the lenses were removed and their center thickness (C) determined. The PLTT was calculated using the equation: PLTT = T-(B+C). Two sets of measurements of T were performed at 15 and 25 minutes after lens insertion. The entire procedure was repeated at a second visit. RESULTS: The pachometry measurements of the small aqueous reservoir between the model eye and the lens closely matched those obtained by direct microscopic measurement. For human PLTT, the mean values (and 95% confidence intervals) for right eyes on visits 1 and 2 were 11 (8, 13) and 12 (10, 15) microm, respectively, and for left eyes were 12 (10, 15) and 11 microm (8, 14) microm, respectively. CONCLUSIONS: It is possible to measure the post-lens tear thickness using optical pachometry. The variability between repeated measurements suggests that with careful sample size planning, the technique is sufficiently precise to be useful in group assessments of PLTT.

Adolescent↗
PubMed1998

Contact lens base curve prediction from videokeratography.

PURPOSE: To assess whether the contact lens to cornea-bearing relationship, as determined from the fluorescein pattern, can be predicted from videokeratography. METHODS: Nineteen non-rigid gas permeable (RGP) lens wearers were each tested for fluorescein patterns with a series of seven RGP contact lenses of different base curves, and compared to a theoretical estimate of the fitting relationship from videokeratography. The experimentally determined alignment lens was then compared to the theoretical alignment (TA) value as determined from the central curvature and eccentricity. RESULTS: The mean difference in lens choice between the TA and experimental alignment (EA) values was -0.01 +/- 0.04 mm and between the simulated keratometric (KA) readings and the EA choice was 0.11 +/- 0.05 mm. CONCLUSION: A knowledge of the eccentricity value from videokeratography allowed a better prediction of the base curve to cornea relationship than was provided by only a central corneal measurement.

Adult↗
PubMed1997

Alignment effects in videokeratography of keratoconus.

PURPOSE: To determine the effects of corneal apex decentration on videokeratography in subjects with keratoconus. We controlled corneal apex decentration by first locating the cone apex position and then shifting the fixation position by known amounts relative to the videokeratograph axis. METHODS: We evaluated the effect of keratoconus apex position on videokeratography by measuring 28 eyes (17 subjects) at 4 corneal positions: the vertex normal, apex, and 1 mm or 2 mm above the apex. RESULTS: When compared to the apex alignment values, the radius of 1 mm (mean difference: 0.27 mm; SD +/- 0.20 mm) and 2 mm (mean difference: 0.82 mm; SD +/- 0.50 mm). The corneal toricity was greater at apex alignment than at the 1 mm (mean: -0.35 D; SD +/- 1.76 D) and 2 mm (mean: 0.62 D; SD +/- 3.23 D) decentrations. CONCLUSIONS: Decentration of the corneal apex in keratoconus produces significant errors in videokeratography when using the standard alignment rather than alignment with the apex. When there is a decentered cone apex, videokeratograph power errors are greater with the standard (sagittal) power map than with the instantaneous (tangential) power map. The standard power map produces values for the apex position that are about 50% too high and values for the apex power that are from 10 to 40% too low. Most cone shapes have significant toricity that is often not detected with standard videokeratograph alignment.

Adolescent↗
PubMed1996

Asymmetric corneal toricity and pseudokeratoconus in videokeratography.

BACKGROUND: The diagnosis of asymmetric corneal toricity in video- keratography is based on the occurrence of an asymmetric bow tie pattern in the corneal map, which is usually attributed to corneal radial asymmetry but can be an artifact produced by misalignment of the videokeratograph with the corneal apex. METHODS: This study determined whether asymmetric bow tie patterns in 16 subjects (ages 24 to 40 years with corneal toricity of 0.37 to 1.50D) could be converted to symmetric bow tie patterns by changing the alignment of the videokeratograph so that it was directed at the corneal apex. RESULTS: In changing from regular to apex alignment the corneal map became more symmetric in 11 eyes, had no change in 3 eyes and increased in 2 eyes. No radius change could be measured centrally, but there were significant changes of greater than 1.00D in the peripheral corneal radii of 8 eyes. CONCLUSIONS: An asymmetric or angled bow tie appearance of a corneal map suggests a decentered apex rather than corneal asymmetry and may lead to a misdiagnosis of the type or magnitude of corneal toricity, keratoconus or other corneal irregularities.

Adult↗
PubMed1995

Location of the major corneal reference points.

INTRODUCTION: The two principal applications of corneal topography are those pertaining to corneal shape, such as contract lens posterior surface design, and those pertaining to corneal power, such as predicting power changes after refractive surgery. Corneal topography measurements for these applications have advantages when related to two major reference points, the corneal apex for shape and the corneal sighting center for power. METHOD: Instantaneous corneal power, toricity, and axis were measured by videokeratography in 20 right eyes using the standard instrument alignment and alignments at each of the 2 major reference points. RESULTS: In comparing the central corneal measurements by videokeratography using the standard alignment to alignment at the corneal sighting center, there were minimal differences of less than 0.50 D for central power, toricity, and axis. In comparing the results for regular alignment to apex alignment there were significant differences for power (greater than 0.50 D) in 5 eyes, toricity in 3 eyes, and axis shifts of greater than 10 degrees in 5 eyes. In comparing the results for the corneal sighting center to apex alignments there were significant differences for power in 4 eyes, toricity in 2 eyes, and axis in 5 eyes. Changes of greater than 1.00 D occurred in the corneal periphery. CONCLUSIONS: In comparing standard videokeratograph alignment to alignment at the corneal sighting center, there were statistically insignificant differences in videokeratography results for corneal power, toricity, and axis. Significantly larger differences were found in comparing standard alignment and alignment at the corneal apex, especially for measurements in the corneal periphery.

Adult↗
PubMed1995

Accuracy of videokeratography for instantaneous radius in keratoconus.

PURPOSE: Present videokeratographs provide corneal radius of curvature measurements in terms of axial (sagittal) radius and, for some instruments, instantaneous (tangential) radius. The EyeSys videokeratograph allows conversion from axial to instantaneous radius based on an algorithm, which assumes a basic corneal shape of elliptical form. METHOD: We tested the accuracy of the EyeSys instantaneous radius algorithm for 29 keratoconic corneas using the criterion that instantaneous radius of the cone apex could be determined accurately by aligning the cone apex with the optic axis of the videokeratoscope. RESULTS: There was a close relation between the instantaneous values obtained from the regular and apex alignments for the 17 eyes with cone apices below 55 D (95% limits of agreement -0.39 to 1.49 D), but not for the 12 eyes above 55 D (95% limits of agreement -4.87 to 6.61 D). The mean distance of the cone position from the center of the map was 1.16 mm for the instantaneous map and 1.59 mm for the axial map. CONCLUSION: Assuming the criterion for accuracy to be the corneal radii found when the videokeratograph was aligned with the cone apex, the instantaneous map for the EyeSys videokeratograph at regular alignment provided reasonably valid measurements for corneas up to 55 D, but large errors existed for some corneas of higher power.

Adolescent↗
PubMed1995

A spline surface algorithm for reconstruction of corneal topography from a videokeratographic reflection pattern.

A videokeratograph quantifies one or more aspects of corneal shape by the computer analysis of a digital image. The image is the reflection formed by illuminating the cornea with a known source pattern. The type of shape information recovered and the accuracy of this information depend upon properties of the computer algorithm used in the analysis. We present a new algorithm that recovers a polynomial spline description of corneal depth.

Algorithms↗
PubMed1995

Shape and refractive powers in corneal topography.

PURPOSE: To compare the relative advantages and disadvantages of four different representations of corneal power--identified as instantaneous, axial, position, and refractive--based on curvature, slope, coordinate position, and focal properties, respectively. METHOD: The four types of corneal power were evaluated by examining their interrelationship for 12 hypothetical corneal shapes chosen to represent the general characteristics of regular, irregular, and surgically altered corneas. RESULTS: There is only a limited association between refractive power and the other three powers, which are based on shape properties. For corneal shapes represented by ellipsoids of low eccentricity (e), refractive power increased as a function of the distance from the reference axis, whereas axial and instantaneous powers were either constant (for e = 0) or decreased, with instantaneous power having the largest decrease. Refractive power decreased for elliptical corneal shapes with eccentricities greater than the reciprocal of the index of refraction, although always decreasing less than the axial or instantaneous power. For various corneal shapes formed by segments of circles (or a polynomial) with large differences in instantaneous power, the refractive power was more closely associated with axial than instantaneous or position powers. CONCLUSIONS: The Purkinje image measurements from videokeratograpy are most closely related to the slope-based axial power because it is slope that determines the direction of reflected rays forming the corneal image. Because of this direct connection, axial power is less sensitive to noise than is refractive, instantaneous, or position power. Present videokeratographs that report axial power provide an approximation of refractive power, but if an exact refractive power is needed it can be calculated easily. Instantaneous power provides the most sensitive measure of local curvature changes, such as those occurring in keratoconus or refractive surgery. There are unique practical applications for each of the four powers.

Cornea↗
PubMed1995

Axial and instantaneous power conversion in corneal topography.

PURPOSE: To determine if a direct relationship exists between the two common measures of corneal topography--axial and instantaneous powers--that are based on corneal slope or curvature, respectively. METHOD: The theoretical relationship between axial and instantaneous powers was derived for unrestricted shapes using equations of basic calculus. RESULTS: It was found that axial power at any point y on the cornea is exactly equal to the average of the instantaneous powers from the axis to point y. CONCLUSIONS: A simple relationship exists between axial and instantaneous powers that is valid for the intersection of any surface by a meridional plane. This provides a practical means for converting between axial and instantaneous powers for clinical applications of corneal topography.

Cornea↗
PubMed1994

Apparent pupil displacement in videokeratography.

With videokeratography, the apparent position of the entrance pupil of some eyes is displaced by up to 0.5 mm from the center of the target ring image or the corneal map. This displacement occurs because of the alignment system and is not affected significantly by the corneal central radius of curvature, peripheral asphericity, or other shape parameters. It is determined primarily by angle lambda between the line of sight and the pupillary axis and is reduced when the real pupil is decentered nasally. The displacement of the entrance pupil position occurs in all commercial videokeratographs and is responsible for the difference in the apparent position of the entrance pupil when observed directly by the examiner's eye, in refractive surgery, and when measured by videokeratography. This difference also demonstrates that the line of sight should represent the primary reference axis for videokeratography and photorefractive surgery rather than the vertex normal or the visual axis.

Cornea↗
PubMed1992

The effect of carboxyl-terminal deletions on the nuclear transport rate of rat hsc70.

Rat brain hsc70 is a constitutively expressed member of the 70-kDa family of heat shock proteins that is capable of bidirectional transport across the nuclear envelope when microinjected into Xenopus oocytes [1]. The objective of this study was to identify domains involved in its bidirectional transport. Limited proteolytic digestion with chymotrypsin generated three major truncated proteins of approximately 67.5, 59.5, and 56.5 kDa. Reactivity with NH2-terminal-specific antibodies showed that carboxyl-terminal fragments were removed. Nuclear uptake studies were performed by microinjecting 125I-labeled proteins into the cytoplasm and determining their subsequent nucleocytoplasmic distribution. The accumulation rates, while faster than bovine serum albumin controls, were inversely related to the size of the truncated proteins and greatly reduced compared to undigested hsc70. Nuclear efflux was assayed by microinjecting labeled proteins directly into oocyte nuclei. The relative efflux rates of the truncated polypeptides were less than the undigested protein, and, as observed for uptake, were inversely related to size. These results indicate that the carboxyl-terminal domain of hsc70 is involved in its bidirectional exchange.

Amino Acid Sequence↗
PubMed1991

Corneal trauma from overnight wear of rigid or soft contact lenses.

To evaluate the mechanical or biochemical insult to the cornea induced by overnight rigid gas permeable (RGP) or soft contact lens (SCL) wear, punctate, stipple staining and corneal blotting were evaluated by biomicroscopy in a group of 23 subjects who participated in a single overnight in-laboratory test session. The soft lens-wearing corneas typically showed greater area of staining along with corneal blotting in comparison to RGP-wearing corneas which showed smaller areas of corneal staining, even in the presence of RGP adherence, and no corneal blotting. We investigated the effect of hypoxia on corneal staining by having subjects wear an RGP lens of Dk = 150 on one eye and a soft lens of Dk = 9 on the fellow eye. Pachometry measurements immediately following eye opening showed an average central corneal swelling of 5 percent for the RGP lens-wearing eye and an average of 11 percent for the SCL-wearing eye. It is likely that the differences in corneal effects of RGP and SCL overnight lens wear are the result of differences in the nature of rigid versus soft contact lens adherence.

Adult↗
PubMed1991

Protein accumulation on disposable extended wear lenses.

We investigated protein accumulation on disposable extended wear contact lenses. Fifteen volunteers were fit with one low water content, non-ionic lens (Bausch & Lomb's SeeQuence) randomly assigned to one eye and a high water content ionic lens (Vistakon's Acuvue) assigned to the fellow eye. During the first 7 weeks of extended wear the lenses were removed weekly for sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of protein deposition, and replacement lenses were inserted. Four subjects completed additional test sessions of 1 minute, 15 minutes, 24 hours, and 1 week extended wear. Lysozyme accumulation, as measured by SDS-PAGE, increased with wearing times up to one week on all Acuvue lenses, but after 24 hours wear lysozyme accumulation did not increase on the SeeQuence lens. Proteins falling into the reported molecular weight ranges of albumin, PMFA, IgG, IgA (sec), lactoferrin and subunits of protein G were evident on all gels at 1 minute of wear, but these protein groups did not have a detectable increase in deposition after 24 hours wear for either the SeeQuence or the Acuvue lenses. In most cases, the protein accumulation evident from SDS-PAGE analysis was not observable by biomicroscopy using standard clinical methods. A few patients reported preference for the initial comfort and vision achieved by the Acuvue lens, but no preference was found after adaptation.

Adult↗
PubMed1990

Identification of two HSP70-related Xenopus oocyte proteins that are capable of recycling across the nuclear envelope.

Two 70-kD polypeptides, B3 and B4, are present in equivalent concentrations in the nucleus and cytoplasm of Xenopus oocytes. The objectives of this study were to determine if they (a) are members of the 70-kD family of heat shock proteins, and (b) recycle between the nuclear and cytoplasmic compartments. Evidence based on high-affinity binding to ATP, cross-reactivity of B3/B4-specific antibodies with rat hsc70, and a comparison of cyanogen bromide cleavage peptide maps with hsc70, verified that B3 and B4 are members of the 70-kD family of heat-shock proteins. Nuclear uptake studies were performed by microinjecting 125I-labeled B3/B4, rat hsc70, and BSA into the cytoplasm of oocytes, and examining their subsequent intracellular distributions. By 6 h postinjection, the nuclear concentration of B3/B4 and hsc70 were approximately 24-fold greater than BSA controls. It was also found that B3/B4-coated gold particles as large as 120A in diameter were able to enter the nucleus by passing through the pores. Nuclear efflux was analyzed by microinjecting the iodinated proteins directly into the oocyte nuclei. 2 h after nuclear injection, at least 46% of the B3/B4 and 60% of the hsc70 were found in the cytoplasmic fractions, compared with less than 10% for the BSA controls. Cell fusion experiments, in which labeled, anucleate oocyte vegetal hemispheres were fused, under oil, with nucleate unlabeled animal hemispheres, demonstrated that cytoplasmic B3 and B4 could enter the nucleus after equilibration was reached, arguing against the existence of separate nuclear and cytoplasmic populations. Collectively, these results show that B3, B4, and rat hsc70 are transported across the nuclear envelope and recycle between the nucleus and cytoplasm.

Amino Acid Sequence↗