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Biomedical subjects

E K Wong

Publications and source records attributed to E K Wong.

16 recordsLinked to original sources

Comparison of natural killer activity of human bone marrow and blood cells in cultures containing IL-2, IL-7 and IL-12.

Previous studies have suggested that autologous bone marrow or mobilized peripheral blood progenitor cell transplants activated by prior culture of the cells in IL-2 may capture some of the beneficial graft-versus-leukemia effects obtained with unmanipulated allogeneic, but not autologous, transplants. To investigate ways of improving this approach,we have compared the ability of two other immunomodulating cytokines, IL-7 and IL-12, either alone or in combination with IL-2, to stimulate human bone marrow cells (BMC) or peripheral blood cells (PBC) to acquire the potential to lyse K562 or Daudi cells. For these studies, we measured the cytotoxic activity of BMC or PBC both before and at the end of their incubation with various cytokine(s) using a standard 51-chromium release assay. Results suggest that IL-2 at optimal concentration induces cytotoxicity significantly higher than IL-7 or IL-12 when tested alone. At optimal concentration, the combination of IL-2 and IL-12 showed a synergistic effect for BMC. Such a synergistic effect could be observed for PBC only when suboptimal concentrations of IL-2 were used. In addition, the ability of the hematopoietic cells to reduce the number of K562 cells remaining at the end of various culture periods in the presence of the cytokines was measured. This was made possible by the use of a G418-resistant K562 cell line which could, in contrast to normal human BMC or PBC, form colonies that wer detectable after 1 week in methylcellulose cultures containing the neomycin analog G418. Normal human PBC, stimulated by either IL-7 or IL-12 alone effectively suppressed K562 proliferation in both of these assays, whereas no activity could be detected when BMC were incubated under the same conditions. On the other hand, cells from both sources displayed anti-leukemic activity when incubated with IL-2 and IL-12 together, although IL-2/IL-12-activated PBC suppressed the growth of co-cultivated K562-neor cells about eight-fold more efficiently than IL-2/IL-12-activated BMC. Cryopreservation and subsequent stimulation of BMC and PBC with cytokines did not cause a significant decrease in cytotoxicity or their ability to inhibit the growth of co-cultivated K562 cells compared to fresh cells. However, the synergistic effect observed with the combination of IL-2/IL-12 was no longer detectable for BMC. These results suggest that (1) PBC are superior to BMC with respect to developing effective natural killer (NK) activity after culture in cytokines and that, (2) the combination of IL-2 and IL-12 may be more effective than IL-2 alone to inhibit proliferation/growth of K562 cells.

Blood Cells

Absorption of fluorescein given under the upper lid.

BACKGROUND: The need for a more efficacious approach to administer topical ocular medications prompted the authors to consider applying conventional eye drops under the upper lid rather than beneath the lower lid. Preliminary observations on patients with glaucoma using a beta-blocker beneath the upper lid suggested a drop in intraocular pressure into the normal range in some previously refractory patients being treated with the same medications. To test this clinical observation, the authors observed if there were any physiologic differences in topical fluorescein absorption into the anterior chamber when given beneath the upper lid versus the lower lid. METHODS: A 5-microliters drop of fluorescein solution was placed under the upper-lid fornix of one eye and under the lower-lid fornix of the other eye in human volunteers, and absorption into the anterior chamber was measured at hourly intervals, for a total of 3 hours. RESULTS: Hotelling T2 multivariate analysis for all 3 hours demonstrates that upper-lid administration of fluorescein results in significantly higher absorption of fluorescein into the anterior chamber than does lower-lid administration (P = 0.0088; for hours 2 and 3, the statistical differences is even more dramatic: P < 0.0044). CONCLUSION: Using conventional eye drops beneath the upper lid, the authors observed increased absorption of fluorescein into the anterior chamber when compared with lower-lid administration. Profuse tearing, especially by younger subjects, significantly and rapidly diminished anterior chamber absorption of fluorescein. It is reasonable to consider further clinical studies to test this new approach to drug delivery.

Absorption

Deformation of orthodontic archwires over time.

Most previous studies of archwire deformation over time (hereafter referred to as "time-dependent deformation of orthodontic wires") have been conducted at a constant room temperature. In the clinical situation however, arch wires are exposed to 37 degrees C as well as to periods of temperature increase when hot foods or fluids are ingested. The effects of the latter on time-dependent behaviour are largely unknown. Since the introduction of direct electric resistance heat treatment to superelastic nickel titanium wires, there have been no reports on its effect on time-dependent deformation. This study investigated the effects of repeated temperature increases (70 degrees C) on stainless steel, nickel titanium and beta titanium wires. The wires were deflected by approximately 3 and 5 mm on two jigs for periods of 1 minute, 1, 7, 14 and 28 days. Permanent deformation was measured optically with a measuring microscope and the amount of time-dependent deformation was calculated. Beta titanium wires demonstrated the greatest amount of time-dependent deformation; followed by non-superelastic nickel titanium, stainless steel, and superelastic nickel titanium. Exposure to repeated temperature (70 degrees C) increases and direct electric resistance heat treatment of superelastic nickel titanium did not affect time-dependent behaviour.

Dental Stress Analysis

Intestinal absorption of dietary fat in patients with multiple sclerosis.

Fat absorption was studied in 24 patients with clinically definite multiple sclerosis and in 36 healthy control subjects. Beta-carotene and vitamin A in their plasma were also measured. This double-blind and randomized study showed no differences between these two populations with regard to the three parameters. We did not find evidence for fat malabsorption in multiple sclerosis.

Adult

A selective mapping algorithm for computer analysis of voided urine cell images.

One of the fundamental targets of the automated image analysis of cytologic preparations is the reduction of computer classification errors due to cells or other objects that do not lend themselves to image segmentation or that have morphologic features that may mislead the cell classification schemes. In prior work from this laboratory, the achievement of this goal was attempted by hierarchical analysis of sequential microscopic objects at high resolution. This paper reports on the successful development and implementation of an automated "selective mapping algorithm" that selects cells at low power for further analysis and eliminates a large proportion of unwanted "objects." The algorithm classifies the objects and extracts appropriate features from a 256 X 240 digital image obtained via a 10 X planachromatic objective. The five-node binary tree classifier used in this triage is described. The algorithm was trained and tested initially on 501 visually classified microscopic "objects," resulting in a correct acceptance rate of 61.3% and correct rejection rate of 81.3%. The selective mapping algorithm was subsequently integrated into the video-based image analysis system constructed at the Montefiore Medical Center for the diagnostic evaluation of sediments of voided urine. The algorithm was then tested on ten cytocentrifuge preparations for a preliminary evaluation of its performance. Up to 100 "objects" per case were selected by the algorithm for further classification by the computer at high power. Of the 810 "objects" selected by the selective mapping algorithm, 344 (42.5%) were classified by the computer at high resolution as cells of diagnostic value ("WELL" cells) and 466 were rejected.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms

An expert system designed as a tutoring tool in cervical cytology: TTCC-1 system.

A knowledge-based intelligent system being developed as a computer-assisted tutoring tool that can be used by teachers and students of cervical cytology is described. This system uses a combination of frames and rules as knowledge representation. Combination data structures called "prototypes" characterize the typical cytoplasmic and nuclear features of classes of cervical cells by using a specific prototype for each hypothesized cell type. A hypothesis-directed approach is used for problem solving. Rules are associated with each prototype or hypothesis. There are two major kinds of rules: deducing rules, used for deducing certainty factors (expressed as degrees of certainty of the hypotheses), and strategy rules, used for guiding the user in reaching a conclusion about the test cell. With an easy-to-use interactive menu, the user inputs a series of sets of qualitative cell features, which the system utilizes at various inference stages and finally arrives at a decision about the cell type.

Cell Biology

First-order Wiener kernel visually evoked potentials obtained from multiple sclerosis patients.

Visually evoked potentials (VEP) were measured in multiple sclerosis patients with five sizes of reversing check stimuli. The VEPs were obtained using random binary sequence triggered check reversals. The random binary sequence was cross-correlated with scalp potential responses to obtain the estimates of the linear response of the system. For each evaluation a series of five VEPs, one for each of five check sizes, was done. A correlation coefficient was calculated to evaluate check size versus amplitude of the major negative wave. A tabulation was made to compare Snellen chart visual acuity with these correlation coefficients. For the eyes with a Snellen acuity of 20/20, 63% of the VEP amplitudes increased as the check size was decreased with correlation coefficients of -0.6 to -1. For the eyes with a Snellen acuity of 20/70 or less the amplitude decreased with the check size decrease, showing a correlation coefficient of +0.6 to +1 in 45% of the evaluations. The check size giving the largest amplitude was also tabulated with respect to the visual acuity, but did not appear to have as strong a relationship to visual acuity.

Evoked Potentials, Visual

Clinical evaluation of the Humphrey automatic refractor.

A new automatic objective refractor was used on healthy adults. In the absence of cycloplegic drugs, spherocylindrical objective refractions performed with the instrument provided 20/20 acuity 96% as often as with standard subjective techniques. No instrument-induced accommodations effects were seen. One hundred percent of instrument spherical findings were repeatable within 0.50 diopters; all cylindrical findings were repeatable within 0.37 D. This result represents a higher level of repeatability than that reported for standard subjective refraction under clinical conditions. In the absence of cycloplegic drugs, the correlation coefficient between the instrument's findings and standard subjective spherical findings was .97 v .98 between two practitioners' subjective refractions. The average difference between cylindrical findings of the instrument and those of an experienced practitioner was 0.04 D larger than the average difference seen between two practitioners using subjective techniques.

Accommodation, Ocular

Erythrocyte membrane 2', 3'-cyclic nucleotide 3'-phosphodiesterase activity in multiple sclerosis.

The specific activities of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase, EC3.1.4.37) in erythrocyte membranes from five patients with active multiple sclerosis (MS) and five normals were compared. The CNPase assay used 2',3'-cyclic NADP as the substrate in an enzyme coupled reaction to produce fluorometrically detectable NADPH. The specific activity of CNPase in the MS and normal groups were 19.2 +/- 2.3 and 28.7 +/- 1.8 mumol/h/mg protein, respectively. The difference was significant with p less than 0.006, based on a one-tailed t-test.

2',3'-Cyclic-Nucleotide Phosphodiesterases

[A hypothesis: multiple sclerosis a systemic disease].

Metallochemical and biochemical studies completed in the Department of Ophthalmology at the University of California, Irvine, offer a new perspective in understanding MS. Low plasma zinc levels were observed in MS patients, and this has been confirmed in laboratories elsewhere in the world. Generalized malabsorption could not be demonstrated in MS patients when using a double-blind, randomized study of 72-hours fecal fat. A double-blind, randomized zinc tolerance test confirmed the low plasma zinc levels in fasting MS patients, but once an oral zinc load had been given, the 7-hour post treatment levels were elevated to that of control patients. Intracellular erythrocyte zinc concentration was measured in controls and in MS patients. The controls had no change over 7 hours despite a large zinc load with consequent elevation in plasma levels. However, MS patients demonstrated a gradual elevation of intracellular zinc concentration over the 7-hour period, with P less than 0.01. Thus, the erythrocyte membranes of controls were able to maintain the zinc gradient between the extracellular and the intracellular compartments, while MS patients were not, suggesting a functional abnormality in plasma membranes outside of central nervous system. Erythrocyte membrane-bound CNP was observed to be abnormality low in MS patients when compared to controls. The study has been confirmed by a different laboratory using a different substrate on MS erythrocytes. The rationale for considering MS as a possible systemic disease is presented.

Carbonic Anhydrases

A study of congenital nystagmus: waveforms.

Eighteen patients with congenital nystagmus were studied with the techniques of electronystagmography and computer analysis. We found several complex wave forms of congenital nystagmus in the primary position of gaze above those of jerk and pendular nystagmus as defined clinically. An etiologic classification of motor fixation defect and sensory fixation defect nystagmus based on waveforms is not justified. Ocular tracking studies demonstrate that the smooth pursuit system is operational in congenital nystagmus and substantiate the belief that the fast component of jerk nystagmus is a corrective movement generated by the saccadic system. Patients with congenital nystagmus are able to produce voluntary saccades with normal velocity-amplitude relationships.

Adolescent

Response to hepatitis B vaccination in a primary care setting: influence of HIV infection, CD4+ lymphocyte count and vaccination schedule.

Factors affecting the response to hepatitis B vaccination in a primary care setting were examined by means of a review of case notes of patients attending 22 sexually transmissible disease services. Where not available from the notes, presence of antibody to hepatitis B surface antigen (anti-HBs) was determined by testing available stored serum. One hundred and ninety-five patients completed a course of 3 injections and had an anti-HBs assay performed. The highest response rate (anti-HBs > or = 10 IU/L) was found in human immunodeficiency virus (HIV)-negative heterosexual women (16 of 17, 94.1%) followed by HIV-negative heterosexual men (11 of 12, 91.7%); HIV-negative homosexual men (105 of 120, 87.5%); and HIV-positive homosexual men (6 of 14, 42.9%). (For HIV-positive vs HIV-negative homosexual men, P = 0.0003). Eleven of 14 (78.6%) homosexual men of unknown HIV status responded to vaccination. There was a trend to lower CD4+ lymphocyte counts among HIV-infected patients who responded to hepatitis B vaccination (mean 482 cells/cm2) when compared to those that did not respond (632 cells) but this difference was not statistically significant (P = 0.330). Neither the type of vaccine (recombinant, plasma-derived or mixed) nor the length of vaccination course (mean 6.2 months; range 2 to 18) affected response. This study confirmed that vaccination against hepatitis B is much less effective in HIV-infected homosexual men and marginally less effective for HIV-negative homosexual men, though the mechanism for this reduced response is uncertain. Reassuringly vaccine response was not affected by common variables in primary care settings such as vaccine type or delays in the vaccine schedule.

Adult