Final Cone Research Articles

Learning effect of dark adaptation among normal subjects

To examine and quantify any change in the dark adaptation (DA) function of normal subjects due to learning effect on test-retest. Sixteen normal subjects (12 women, four men) whose ages ranged between 24 and 52years (mean 34.6 ± 6.7years) were studied. The interval period between test and retest ranged between 0.92 and 2.37months (mean 1.38 ± 0.40months). DA was measured with a Goldmann-Weekers (GW) dark adaptometer, and subjects were pre-adapted using a light intensity of 2,700cd/m(2) Ganzfeld background for 5 minutes. Exponential non-linear regression analysis was used to determine seven parameters of DA function. These were time of cone-rod break, cone and rod final thresholds, and magnitude of change and time constant of the cone and rod limbs. The mean cone-rod break time with 95% confidence intervals (CI) was 0.098 (CI: -0.527, 0.330) minutes faster on retest (p = 0.630)). Fourteen of the 16 subjects demonstrated an increase or 'worsening' of their final cone and rod thresholds on the second visit. The mean final threshold differences on retest for the cone limb was 0.105 (CI: 0.032, 0.179) log cd/m(2) (p = 0.008) and 0.093 (CI: -0.039, 0.225,) log cd/m(2) (p = 0.155) for the rod limb. The magnitude of change for the cone limb was 0.016 (CI: -0.122, 0.155) log cd/m(2) (p = 0.805) and -0.196 (CI: -0.435, 0.827) log cd/m2 (p = 0.518) for the rod limb, while the time constant on retest for the cone limb was -0.021 (CI: -0.128, 0.169) minutes, (p = 0.770) and 0.276 (CI: -0.424, 0.976) minutes (p = 0.410) for the rod limb. None of the DA parameters that were examined demonstrated a learning effect of clinical significance between test and retest. None of the changes in mean from test to retest for the seven parameters were found to be statistically significant, and the changes were clinically negligible. Therefore, any change among patients that may occur in dark adaptation between a visit interval may be considered real, and not due to the effect of learning.

Automatic Determination of the Conic Coronal Mass Ejection Model Parameters

Characterization of the three-dimensional structure of solar transients using incomplete plane of sky data is a difficult problem whose solutions have potential for societal benefit in terms of space weather applications. In this paper transients are characterized in three dimensions by means of conic coronal mass ejection (CME) approximation. A novel method for the automatic determination of cone model parameters from observed halo CMEs is introduced. The method uses both standard image processing techniques to extract the CME mass from white-light coronagraph images and a novel inversion routine providing the final cone parameters. A bootstrap technique is used to provide model parameter distributions. When combined with heliospheric modeling, the cone model parameter distributions will provide direct means for ensemble predictions of transient propagation in the heliosphere.

Should Unsatisfactory Colposcopy Necessitate Treatment of Cervical Intraepithelial Neoplasia 1?

To evaluate the prevalence of cervical intraepithelial neoplasia (CIN) 2 or worse among women undergoing cone biopsy for CIN 1, stratified by colposcopic adequacy. A cross-sectional cohort study was performed using a colposcopic database of 3,004 women seen between August 1999 and December 2005. Data collected included demographic information, indications for treatment, adequacy of colposcopic examination, and final cone pathology. A satisfactory colposcopy was defined as being able to define the entire squamocolumnar junction and visualize all lesions in their entirety. Descriptive statistics and crude and adjusted odds ratios with 95% confidence intervals were calculated. Of the 440 cone biopsies, 50 (11%) were done for CIN 1, of which 9 (18%) demonstrated CIN 2 or worse, and 23 (46%) were done in the setting of unsatisfactory colposcopy. Compared with women with satisfactory colposcopy, women with unsatisfactory colposcopy were more likely to be older (median age = 33 vs 25 years, p = .01) and to have CIN 1 on endocervical sampling (5/22 [22%] vs 0, p < .01). Persistent (18 months or more) CIN 1 was more commonly encountered in women with satisfactory colposcopy (21/27 [78%] vs 7/23 [30%], p < .01). Women with unsatisfactory colposcopic examinations were at decreased risk of CIN 2+ on final pathology compared with women with satisfactory examinations (1/23 [4%] vs 8/27 [30%], odds ratios = 0.08, 95% confidence intervals = 0.01-0.95). Women with unsatisfactory colposcopy and CIN 1 are unlikely to have high-grade cervical neoplasia on final pathology. For this subset of women, conservative management is preferable to immediate treatment.

Differentiation of cones in cultured rabbit retina: effects of retinal pigment epithelial cell-conditioned medium

This study was aimed at investigating the postnatal differentiation of cone photoreceptors in the rabbit retina in an organotypic explant culture system. Both short wavelength (S) and middle wavelength (M) cone opsins were expressed in culture but M cones appeared only in retinal explants from the dorsal half of the eye. Stimulating the explants with retinal pigment epithelial cell (RPE) conditioned medium resulted in a suppression of opsin expression despite of an increase of the number of presumptive peanut agglutinin-labeled cones. These results suggest that at birth the immature cones are largely undetermined in terms of their final cone identity although some positional information (‘dorsal’ vs. ‘ventral’ retina) is present. Furthermore, factors from RPE may inhibit as well as stimulate different steps of cone cell differentiation.

Condition for adiabatic passage in the earth’s-field NMR technique

The equation of motion d M / dt=γ M × B (t) is solved for the case B (t)= j B p (t)+ k B e . The field B e is a small static field, typically the earth’s field. The field B p( t) decays exponentially toward zero with time constant T. This decay is produced by an overdamped switching transient that occurs near the end of the rapid cutoff of the coil current used to polarize the sample. It is assumed that B p is initially large compared to B e, and that magnetization M is initially along the resultant field B. Exact solutions are obtained numerically for several decay time constants of B p, and the motion of M is depicted graphically. It is found that for adiabatic passage, the final cone angle β of the precession in field B e is related to the decay time constant of B p by β=2e −(π/2) ω e T . This is confirmed by measurements of the amplitudes of the ensuing free-precession signals for various decay rates of B p. Near-perfect adiabatic passage (magnetization aligned within 2° of the earth’s field) can be achieved for time constants T⩾2.6/ ω e. For the case of sudden passage, an approximate analytic solution is developed by linearizing the equation of motion in the laboratory frame of reference. For the adiabatic case, an approximate analytic solution is obtained by linearizing the equation of motion in a rotating frame of reference that follows the resultant field B = B p + B e .

Effects of fenretinide (4-HPR) on dark adaptation.

To assess the alterations in dark adaptation induced by low (200 mg/d) doses of fenretinide (4-HPR), to assess whether these effects were cumulative and whether they were reversible, and to attempt to elucidate the mechanism underlying the changes in night vision. Case series. Outpatient eye clinic. Twenty-two women enrolled in a breast cancer chemoprevention trial, and 18 normal control subjects. Measurements of absolute luminance thresholds during dark adaptation. Parameters of an exponential model of the dark-adaptation function before, during, and after administration of fenretinide. The most conspicuous effect of fenretinide on dark adaptation was a significant delay in the timing of the rod-cone break (P<.001). A minimal elevation of the final cone threshold was also observed. These effects were reversible after fenretinide therapy was discontinued and did not seem to be cumulative. An inverse relationship between delay of the rod-cone break and plasma retinol concentration was found. The dose of fenretinide used in this study produced clearly measurable, but not severe, changes in night vision, which were rarely symptomatic.

Fabrication and characterization of optical-fiber nanoprobes for scanning near-field optical microscopy

The current scanning near-field optical microscopy has been developed with optical-fiber probes obtained by use of either laser-heated pulling or chemical etching. For high-resolution near-field imaging, the detected signal is rapidly attenuated as the aperture size of the probe decreases. It is thus important to fabricate probes optimized for both spot size and optical transmission. We present a two-step fabrication that allowed us to achieve an improved performance of the optical-fiber probes. Initially, a CO(2) laser-heated pulling was used to produce a parabolic transitional taper ending with a top thin filament. Then, a rapid chemical etching with 50% buffered hydrofluoric acid was used to remove the thin filament and to result in a final conical tip on the top of the parabolic transitional taper. Systematically, we obtained optical-fiber nanoprobes with the apex size as small as 10 nm and the final cone angle varying from 15 degrees to 80 degrees . It was found that the optical transmission efficiency increases rapidly as the taper angle increases from 15 degrees to 50 degrees , but a further increase in the taper angle gives rise to important broadening of the spot size. Finally, the fabricated nanoprobes were used in photon-scanning tunneling microscopy, which allowed observation of etched double lines and grating structures with periods as small as 200 nm.

Cutaneous Melanoma-Associated Retinopathy

Purpose: To define further the syndrome of cutaneous melanoma-associated retinopathy, of which only five affected patients have been reported previously. Methods: Three men with melanoma-associated retinopathy were examined and studied electrophysiologically. Two were studied in detail psychophysically. Results: Visual symptoms consisted of flickering black and white spots, shimmering patches of colors, and night blindness. The onset was acute and nonprogressive. Reduced amplitudes were observed in the flash electroretinographic b-wave and the pattern electroretinogram. Color vision, contrast sensitivity, and light- and dark-adapted perimetric sensitivities were abnormal. In one patient, the rate of dark adaptation was normal with elevated final cone and rod thresholds. Conclusions: Melanoma-associated retinopathy is a paraneoplastic syndrome distinct from cancer-associated retinopathy with a different visual prognosis. It may preferentially affect men.

Cutaneous Melanoma-associated Retinopathy

To define further the syndrome of cutaneous melanoma-associated retinopathy, of which only five affected patients have been reported previously. Three men with melanoma-associated retinopathy were examined and studied electrophysiologically. Two were studied in detail psychophysically. Visual symptoms consisted of flickering black and white spots, shimmering patches of colors, and night blindness. The onset was acute and nonprogressive. Reduced amplitudes were observed in the flash electroretinographic b-wave and the pattern electroretinogram. Color vision, contrast sensitivity, and light- and dark-adapted perimetric sensitivities were abnormal. In one patient, the rate of dark adaptation was normal with elevated final cone and rod thresholds. Melanoma-associated retinopathy is a paraneoplastic syndrome distinct from cancer-associated retinopathy with a different visual prognosis. It may preferentially affect men.

ALTERED MONONUCLEAR CELL IMMUNE RESPONSE IN WOMEN EXPOSED TO DES IN UTERO

In utero diethylstilbestrol (DES) exposure results in long term reproductive consequences. Preliminary evidence suggests a link between prenatal DES exposure and long term alterations in the immune system. To further test this hypothesis, we compared the phytohemaglutinin (PHA) and concavlin A (con A) induced blastogenic response of mononuclear cell in prenatally exposed women (n=13) to age matched non DES exposed women (n=9). 15 ml. of whole blood obtained during the early follicular phase of cycling women were heparinized, diluted 1:2, layered over ficoll-paqun density gradient. The mononuclear cells were washed X 3 (10%, R.P.M.I. 1640). Aliquots (final cone, of 5 × 105ml). Either PHA (7.5ug-1ug/ml) or Con-A were added to each well. After 48 hours of incubation at 37° C the cells were pulsed with 1 Cμ-thymidine(H-Td), reincubated for 18 hours, harvested, counted, and a geometric mean of 3 determinations obtained.Results: Decreasing H-Td proliferation responses paralleled declining mitogen concentrations both with PHA and Con-A. Con-A showed no significantly different response in cells from DES subjects compared to controls. In contrast, PHA responses were greater in DES subjects (p<.005 2 way ANOVA).These data indicate long lasting effects on the immune system in DES exposed women. Such lasting effects on the immune system may be accounted for by a genomic mechanism altering the cellular responses in daughter cells throughout the reproductive years.

Cytobrush in Evaluation of Cervical Dysplasia

203 patients suspected of having dysplasia were evaluated by colposcopy, cytologic smear including cytobrush, endocervical curettage, biopsy and conization. The results obtained on the basis of the final cone suggested that directed biopsies and cytological smear by spatula and cytobrush more accurately define the dysplastic lesion than do biopsies and endocervical curettage. Conization seemed necessary for the evaluation of the cervical lesion in patients revealing non-classified dysplasia at successive examinations.

Cytobrush in Evaluation of Cervical Dysplasia: Is Cervical Curettage Necessary?

203 patients suspected of having dysplasia were evaluated by colposcopy, cytologic smear including cytobrush, endocervical curettage, biopsy and conization. The results obtained on the basis of the final cone suggested that directed biopsies and cytological smear by spatula and cytobrush more accurately define the dysplastic lesion than do biopsies and endocervical curettage. Conization seemed necessary for the evaluation of the cervical lesion in patients revealing non-classified dysplasia at successive examinations.

Autosomal Dominant Congenital Stationary Night Blindness and Normal Fundus With an Electronegative Electroretinogram

We studied three members of three successive generations of a family with autosomal dominant congenital stationary night blindness and normal fundi. Psychophysical studies on two members showed normal final cone thresholds and mildly increased rod thresholds. Full-field electroretinograms on all three members showed normal photopic b-wave amplitudes and implicit times. Under scotopic conditions, the rod response was absent, and with a bright flash stimulus, there was a normal a-wave with no b-wave. This electronegative dark-adapted electroretinogram resembled the Schubert-Bornschein type seen in congenital stationary blindness, which has been seen only in autosomal and X-linked recessive pedigrees.

Spin re-orientation transition and high field magnetostriction in ErFe 10V 2

A.C. initial magnetic susceptibility measurements on the intermetallic compound ErFe 10V 2 show the presence of a spin re-orientation transition from axis to cone which commences at 60K and culminates in a final cone magnetic structure of some 45 degrees to the c-axis at 4.2K. The axis to cone transition has been accounted for in a crystalline electric field-exchange model with inclusion of crystal field terms up to 4th order. The anisotropic and volume magnetostrictions have been measured in pulsed magnetic fields of up to 12 Tesla down to 77K. Both the anisotropic and volume magnetostrictions are found to be small at low temperatures. The volume magnetostriction increases with increasing temperature.

The Measurement of Platelet Aggregation and ATP-Release in Mice with Liver Damage Induced by Carbon Tetrachloride (CCl4) Using a Whole Blood Aggregometer

Time course change in platelet function on liver damaged mice was studied by a whole blood aggregometer. The liver damaged animals were produced by single and multiple injections (p.o.) of 20% CCI4 in olive oil to ddY mice (6 weeks). Platelet aggregation and ATP-release were induced with collagen (final cone, of 2 μg/ml), ADP (final cone, of 20 μM) and arachidonic acid (AA: final cone, of 100 μM). After a single injection of CCl4, platelet counts increased at 5 and 1 2 hr, and then they decreased from 24 to 1 20 hr. Multiple injections of CCl4 resulted in a significant increase in platelet counts. A single injection of CCl4 suppressed aggregation by collagen at 24 and 48 hr and diminished the rate of ATP-release from 12 to 48 hr. AA-induced platelet aggregation was depressed at 48 hr, and ATP-release was also diminished from 24 to 72 hr after a single injection. ADP-induced platelet aggregation was decreased 24 and 48 hr after a single injection and at 48 hr after multiple injections, while, the rate of ATP-release by ADP was significantly increased after single and multiple injections. These changes in platelet functions might be consistent with our original report on the alterations in coagulative and fibrinolytic activities with CCl4-induced liver injury.

Cone adaptation in age-related maculopathy.

Cone adaptation was measured in patients with age-related maculopathy (ARM) and age-matched controls. A red stimulus was used to selectively bias responses toward cone function and adaptation was measured 5, 10, 20, and 40 degrees eccentric to fixation. The ARM patients' thresholds were elevated by 1 log unit at 5 and 10 degrees, with the threshold difference reducing to 0.5 log units at 40 degrees. Curves of the form log (threshold luminance) = ae-bt + c (where t is time and a, b, and c are constants) were fitted to each adaptation curve; a procedure involving differentiation of the above equation was used to estimate the constant parameters. Time constants of cone recovery (1/b) were derived for each fitted curve. No significant difference was found between the time constants of the two test groups. Our data suggest that cone adaptation is significantly affected in patients with ARM, with raised cone thresholds occurring for areas well into the peripheral retina. We suggest that the effect is mediated by a reduction in the number of functional cones, which elevates the final cone thresholds without altering the adaptation time constant. Our findings imply that age-related "maculopathy" may not be confined to the macular area, and that early signs of the degeneration may be present in the peripheral retina even when central acuity is normal.

Heme synthetase in Trypanosoma cruzi

1. 1. Heme-synthetase (Heme-S) has been studied in the epimastigote form of T. cruzi (Tulahuen and Y strains). 2. 2. The enzyme is confined to the “mitochondrial” fraction (sedimented at 30,000 g). 3. 3. Activity was dependent on protein and time of cell storage. 4. 4. Enzymic proto- and meso-heme formation was inhibited up to 40 and 72% respectively by Triton X-100. 5. 5. The optimum pH was 7.2 for protoheme and 7.5 for mesoheme formation. 6. 6. Heme-S reached its maximum when the concentration values were 37; 35 and 32 μM for proto-, meso-, and deuteroporphyrin, respectively. The activity is several times higher when mesoporphyrin is used as substrate. 7. 7. At a final cone of 100 μM Fe 2+ and Zn 2+ ions enhanced activity 200–400%. Cu 2+ and Co 2+ had no effect, while Mn 2+ and Mg 2+ were highly inhibitory. A combination of Fe 2+ and Zn 2+ at varying concentrations still showed great activation. However, at a fixed level of Fe 2+, Cu 2+ was changed into a strong inhibitor. 8. 8. We propose that, if it can be demonstrated that T. cruzi cannot multiply when protoheme is replaced by mesoheme, administration of mesoporphyrin would then greatly affect replication of T. cruzi. Furthermore, the addition of certain metals, such as Cu 2+ to T. cruzi cultures might specifically inhibit the parasite enzyme opening the possibility of selectively destroying the hemoflagellate without affecting the host.

714 AMINO-ACID (AA) INDUCED REDUCTION OF BILE FLOW IS INDEPENDENT OF TAUROCHOLATE (TC) TRANSPORT

Studies in vivo and in perfused rat liver have reported AA induced decrease in bile flow, but conflicting effects on bile salt transport. We studied the effect of a synthetic AA solution (Aminosyn) on bile flow and TC transport in the isolated perfused rat liver. After a 30 min bile collection period, livers of 12 male Sprague-Dawley rats were perfused with KRB buffer, 2 gm% albumin and .1 gm% dextrose in a recirculating oxygenated system for eight 15 min intervals. 14C-TC was continuously infused at 0.25 uM/min. After the initial four 15 min intervals (Period 1), 0.25 gm AA (final cone. 0.1 gm%) was added to the perfusate of six rats (for Period 2). There was no difference between experimental and control rats in weight, pre-perfusion bile flow rate, O2 consumption, perfusion pressure or flow rate. After initial stabilization, 14C TC secretion and bile flow rate were measured.CONCLUSIONS: 1) Physiologic portal vein concentrations of AA persistently decrease bile flow rate. 2) Initial TC secretion rate is transiently decreased by AA (P<.05, data not shown) but returns to control levels without concomitant recovery of bile flow rate. 3) Steady state TC secretion rate is unchanged by AA. 4) These results suggest that AA influence bile water flux via mechanisms unrelated to bile salt transport.

Decolorization and Degradation Products of the Melanoidins by Hydrogen Peroxide

Nondialyzable melanoidins prepared from a glucose–glycine system were incubated with glucose oxidase under optimal conditions and then the melanoidins were decolorized to 65%. The decolorization of melanoidins by glucose oxidase may be mainly caused by hydrogen peroxide produced from the enzyme-substrate reaction. Therefore, oxidative decomposition and decolorization of melanoidins were tried using hydrogen peroxide. Melanoidins were treated with hydrogen peroxide (final cone. 6.72%) under neutral (pH 7.0) and alkaline (pH 10.0) conditions at 37°C for 28 hr. Melanoidins were decolorized to 64% and 97%, respectively the under above optimum conditions. The mean molecular weight of melanoidins decreased from 5,300 to 3,500 after hydrogen peroxide treatment. The major components in the ether-soluble fraction obtained from melanoidins by oxidative degradation of alkaline hydrogen peroxide were identified as 2-methyl-2,4-pentanediol, N,N-dimethylacetamide, phenol, acetic acid, oxalic acid, methylpropanedioic acid, propanedioic acid, 2-furancarboxylic acid, butanedioic acid, 2-hydroxypropanoic acid, 2,5-furandicarboxylic aicd and 5-(hydroxymethyl)-2-furancarboxylic acid. On the other hand, the major degradation product in aqueous fraction was identified as glycine, and glycine was produced in 1.73% yield per nondialyzable melanoidin.

Decolorization and degradation products of the melanoidins by hydrogen peroxide.

Nondialyzable melanoidins prepared from a glucose-glycine system were incubated with glucose oxidase under optimal conditions and then the melanoidins were decolorized to 65%. The decolorization of melanoidins by glucose oxidase may be mainly caused by hydrogen peroxide produced from the enzyme-substrate reaction. Therefore, oxidative decomposition and decolorization of melanoidins were tried using hydrogen peroxide. Melanoidins were treated with hydrogen peroxide (final cone. 6.72%) under neutral (pH 7.0) and alkaline (pH 10.0) conditions at 37°C for 28hr. Melanoidins were decolorized to 64% and 97%, respectively the under above optimum conditions. The mean molecular weight of melanoidins decreased from 5, 300 to 3, 500 after hydrogen peroxide treatment. The major components in the ether-soluble fraction obtained from melanoidins by oxidative degradation of alkaline hydrogen peroxide were identified as 2- methyl-2, 4-pentanediol, Af, 7V-dimethylacetamide, phenol, acetic acid, oxalic acid, methylpropanedioic acid, propanedioic acid, 2-furancarboxylic acid, butanedioic acid, 2-hydroxypropanoic acid, 2, 5-furandicarboxylic aicd and 5-(hydroxymethyl)-2-furancarboxylic acid. On the other hand, the major degradation product in aqueous fraction was identified as glycine, and glycine was produced in 1.73% yield per nondialyzable melanoidin.