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Biomedical subjects

M Alpern

Publications and source records attributed to M Alpern.

At least 19 recordsLinked to original sources

Dark-light: model for nightblindness from the human rhodopsin Gly-90-->Asp mutation.

A human rhodopsin mutation, Gly-90-->Asp (Gly90Asp), cosegregated with an unusual trait of congenital nightblindness in 22 at-risk members of a large autosomal dominant kindred. Although rhodopsin mutations typically are associated with retinal degeneration, Gly90Asp-affected subjects up to age 33 did not show clinical retinal changes. Absolute threshold for visual perception was elevated nearly 3 logarithmic units in 7 individuals tested (ages 11-64), indicating greatly compromised rod threshold signaling. However, in vivo rhodopsin density was normal. Although the 38-year-old proband could not perceive dim lights, his rod increment threshold function was normal on brighter backgrounds. The impaired rod vision for dim but not bright backgrounds is consistent with a mechanism of increased basal "dark-light" from thermal isomerization equivalent to an increase of > 10(4) over that of wild-type rhodopsin. The Gly90Asp mutation on the second transmembrane helix places an extra negative charge in the opsin pocket; this could contribute to partial deprotonation of the retinal Schiff base and thereby increase photoreceptor noise. In vitro evidence had suggested that transducin is activated by the Gly90Asp mutation in the absence of both the retinal chromophore and light, termed "constitutive activity." The apparent preservation of functioning rods despite extensive and lifelong night-blindness in this kindred is inconsistent with one current hypothesis that chronic rod activation from constitutively active mutant rhodopsin necessarily contributes significantly to photoreceptor demise in human retinal dystrophies.

Adolescent

TMJ biocompatible orthodontic treatment.

The papers summarized here indicate that TMJ dysfunction remains a complicated problem, requiring a multidisciplinary team approach. Psychological stress is an important factor in diagnosis. New concepts of joint function must be considered. The functional anatomy of the TMJ from an arthroscopic perspective should be studied. New treatment methods, such as the polycentric hinge joint articulator, should be considered. And finally, orthodontic diagnosis and treatment conventions need to be modified, from obtaining a complete history, clinical examination, arriving at a diagnosis and obtaining informed consent for treatment that may include psychological counseling, splint therapy, simultaneous fixed orthodontics and splint therapy and possible TMJ arthroscopic surgery for nearly all orthodontic patients.

Arthroscopy

Can computed tomography of the chest stage lung cancer? Yes and no.

To determine the accuracy of computed tomography (CT) of the chest in the staging of lung cancer, we studied 418 patients with primary pulmonary carcinoma between 1979 and 1986. Each had a preoperative scan performed before detailed operative staging. Each CT scan was analyzed for components of the current TNM staging system. Computed tomography sensitivity and specificity for mediastinal lymph node metastasis were 84.4% and 84.1%, with corresponding positive and negative predictive accuracies of 68.7% and 92.9%, respectively. When TNM stages were derived from CT scans, only 190 of 418 (45.4%) completely agreed with operative staging. An additional 53 of 418 (12.7%) predicted the correct stage, although components of the TNM system were incorrect. In 94 of 418 scans (22.5%) CT overestimated the stage, whereas in 81 (19.4%) CT downgraded the stage. Computed tomography suggested metastatic lesions in liver, lung, adrenal gland, bone, or abdominal lymph nodes in 40 of 373 scans (10.7%); only five of 40 (12.5%) had documented metastasis. In summary, CT of the chest cannot accurately stage primary lung carcinoma according to the TNM classification. Because the negative predictive accuracy for mediastinal lymph node metastasis remains high (92.9%), invasive staging can be deferred for definitive thoracotomy when no lymphadenopathy is evident on CT. The high negative predictive accuracy for scans of the chest and upper abdomen makes CT a useful tool for exclusion of metastatic disease.

Adenocarcinoma

Do deviations from radiance-invariance of metameric matches contradict the three pigment theory of foveal trichromacy?

According to the pigment theory of matching, metameric matches result from the equation of the rates of photoisomerizations for each of the three classes of cone pigments excited by the two matched fields. If true, matches are radiance-invariant and additive. Tests of the theory in this paper show small but ubiquitous failures in radiance-invariance due to systematic rather than random errors in matching. A choice between two possible explanations for these systematic errors favors the view that in subjects who deliberately or intuitively search for the middle of the matching range, the errors are due to an asymmetry in the Weber fraction for color (Trezona) at low (but not high) levels of retinal illuminance.

Analysis of Variance

The change in the neutral point of dichromats with change in the angle of incidence of monochromatic light on the retina.

The hypothesis was tested that the change in the perceived color of monochromatic light with change in its angle of incidence on the retina can be accounted for completely by prereceptor factors alone. This was evaluated by measuring the change in the match of a monochromatic light to a fixed (and normally incident) white light as the monochromatic beam changed its traverse through the eye from chief ray to "off-axis" retina incidence at the margin of the exit pupil. Two protanopes and four deuteranopes were tested. In each case, the wavelength of the chief ray at the match was consistently, reliably, and (statistically) significantly larger than that of the match with the "off-axis" beam. The result cannot be accounted for by prereceptor factors alone.

Color Perception

The change in color matches with retinal angle of incidence of the colorimeter beams.

Differences between W.D.W. chromaticities of monochromatic lights obtained with all colorimeter beams incident on the retina "off-axis" and those found for lights striking the retina normally have been studied throughout the visible spectrum on 4 normal trichromats. The results are inconsistent with: (i) the assumption in Weale's theories of the Stiles-Crawford hue shift that the sets of absorption spectra of the visual pigments catching normally and obliquely incident photons are identical, and (ii) "self-screening" explanations for the change in color with angle of incidence on the retina. The color matching functions of a protanomalous trichromat are inconsistent with the hypothesis that the absorption spectra of the visual pigments catching normally incident photons in his retina are those catching obliquely incident photons in the normal retina.

Color Perception

"Self-screening" of rhodopsin in rod outer segments.

Microspectrophotometry (MSP) shows rhodopsin highly concentrated (about 3.0 mmol/l) in rod outer segments (ROS). Calculation of the in vivo absorption spectrum of human rhodopsin from such data reveals a striking failure to agree with the action spectrum of human rod vision. Agreement is good between the spectral distribution of absorption coefficients and the action spectrum, but the "concentration-broadening" (or "self-screening") introduced by the high end on absorbance at this concentration results in a misfit among the largest in the 93 years comparisons of this kind have been made! To deal with this anomaly, it has been suggested that "concentration-broadening" is inappropriate for rhodopsin in rod vision. This proposal was tested by comparing rod action spectra of 15-day-old and adult rats, since the lengths of ROS increase by a factor of about two in maturation. Three lines of evidence are inconsistent with it. Although the conundrum remains unexplained, it cannot be dismissed by supposing "self-screening" inappropriate for night vision.

Aging

A note on the action spectrum of human rod vision.

A template representing the spectral distribution of the absorption coefficients of human rhodopsin was fitted to each of 59 individual action spectra of human rod vision (from one of three populations) by an optimization routine. Curve-fitting parameters included peak wavenumber, optical density at this wavenumber and (for those from the population neither aphakic nor constrained to ages where the standard lens transmissivity curve is supposed valid), density of the latter at the wavenumber of peak lens absorption. The average peak wavenumber of each population differed significantly from that of the other two. Either the standard curve of lens absorption (even with peak lens density as a curve-fitting parameter) is inappropriate for correcting the normal spectrum or the rhodopsins in the retinas of these populations do not all have identical wave-numbers of peak absorbance.

Adolescent

The Stiles-Crawford effect of the second kind (SCII): a review.

The background which led Stiles to the discovery that the color of a monochromatic ray of light varied with its angle of incidence on the retina, and the developments in the subject since 1937 when this discovery was reported are summarized. Stiles's original measurements of the 'hue shift' did not successfully quantify SCII in every part of the spectrum, since it provided only two degrees of freedom while the color changes sometimes require three. Nevertheless, they were the paradigm for most subsequent work for the next quarter of a century. Full quantification of the effect was first obtained by trichromatic matching on Stiles's NPL trichromator almost 25 years after the initial discovery. The phenomena were then also fully described quantitatively with an elaboration of Stiles's original theory ('self-screening' theory), on the assumption that the ordinary laws of additivity are valid for color matches of three primaries striking the retina at one angle of obliquity to a test incident at a different angle. More recent experiments suggest that this initial assumption may not be generally true and that 'self-screening' theory may not generally provide a satisfactory description of the color changes throughout the visible spectrum, even for measurements of the effect obtained under conditions in which the additivity assumption seems to be valid. However, the available data strongly imply that absorptions of photons obliquely incident on foveal cones depend upon spectra clearly different from those upon which absorptions of normally incident photons depend.

Color Perception

Electroretinograms evoked by sinusoidal excitation of human cones.

The amplitude and phase of the fundamental Fourier component of the human electroretinogram (e.r.g.) were recorded with a synchronous detection method under conditions in which each of the three species of cones can be assumed most sensitive in turn. Weber-Fechner behaviour is well established at, or more distal in the retina than, the source of these voltages. Results over the frequency range 7-50 Hz exclude a diffusion model of human flicker perception. The e.r.g. phase vs. frequency plot found with a 'red' test differs from that obtained with a 'green'. The shapes of the e.r.g. field sensitivity action spectra agree with those of the subject's IIj(mu) (j = 3, 4 and 5) mechanisms of Stiles and with in situ measurements of the absorbance spectra of human cone pigments. Threshold phase with each test was independent of background wave-length but, consistent with the results in 3, the phase of the response to the 'red' test (25 Hz) differed significantly from that to the 'green'. If these differences resulted from the absorption of test photons of different colours at different points along the outer segment (independent of cone spectral sensitivity), they would be as clear on dichromats as on trichromats. Results on a protanope are inconsistent with this prediction. We infer that differences in phase are due to the different kinetics of different cone mechanisms and that the e.r.g.s studied here are evoked by exciting only the most sensitive cone mechanism, even though dark-adaptation studies prove that at e.r.g. threshold the test is well above psychophysical threshold for all three cone species. If the inference in 5 is correct, studies of sensitivity across the retina suggest that the spatial distribution of long-, middle- and short-wave-sensitive cones in the human retina differ remarkably.

Dark Adaptation

Factors influencing threshold of the fundamental electrical response to sinusoidal excitation of human photoreceptors.

The amplitude and phase of the fundamental Fourier component of the electroretinogram (e.r.g.) in response to sinusoidally modulated light were studied in the range 7-50 Hz. Sensitivity was best at the lowest frequency. The threshold-frequency relationship divided into two parts. A weak steady background depressed sensitivity of the low, but increased sensitivity of the high, frequency component. At 8 Hz a small test spot was 0.7 log10 units more effective on the most sensitive part of the retina than on the optic disk. On the fovea, it was 0.1-0.2 log10 units less effective than on the disk. The fovea was 0.7 log10 units more sensitive to 25 Hz than the blind spot. Psychophysical and e.r.g. dark-adaptation curves were similar, but the former was 10(4) times more sensitive than the latter. Four sets of experiments examined the possibility that the Fourier component of the e.r.g. response at the modulation frequency of 8 Hz during the 'rod' phase of the e.r.g. dark-adaptation curve arose from excitation of rods alone. The only hint of a possible cone contribution was a very small but systematic increase in phase delay with increase in background wave number found while measuring the field sensitivity action spectrum. No suggestion was found that the fundamental Fourier component of threshold e.r.g. responses at the modulation frequency of 25 Hz was influenced by photons absorbed in rods.

Adult

Classical tritanopia.

1. A subject who has suffered from central serous chorio-retinopathy in his left eye noticed differences in the colour of a given light as perceived by each eye alone. Standard screening tests (colour order and colour matching) indicated a tritan defect in the left eye; the right eye was normal on these tests.2. The subject was dichromatic in his left eye, trichromatic in his right. The left-eye distimulus colour-matching functions, spectral luminosity, and wave-length discrimination functions were indistinguishable from corresponding data for congenital tritanopia. Comparable right-eye data were normal.3. Spectral dichromatic colour matches were invariant under changes of intensity and under addition of a common light to both halves of the field. (Grassmann's laws of linearity are satisfied.)4. Increment threshold versus intensity (t.v.i.) curves for a blue (481.9 nm) test on a yellow background yielded the normal three branches (for Pi(4)(mu), Pi(1)(mu) and Pi(3)(mu) respectively) in the trichromatic eye. In the dichromatic eye a single mechanism was found. It had the field sensitivity of Pi(4)(mu) whether measured with the blue, or with a violet (429.5 nm) test. No trace of Pi(3)(mu) or Pi(1)(mu) was ever discovered in the tritanopic eye. Both are normal in the trichromatic eye.5. The field sensitivities of Pi(4), Pi(5) and Pi(3) of the normal eye are well fitted by linear combinations of the spectral colour-matching functions of the trichromatic eye. Pi(4) and Pi(5) of the dichromatic eye are well fitted by linear combinations of the tritanopic matching functions.6. Colour matches made by the trichromatic eye do not match when viewed by the tritanopic eye, almost certainly because the ocular media of the two eyes have wave-length-dependent differences in absorption. For the largest difference (430 nm) the trichromatic eye transmits about 2.2 times more light than its fellow. When allowance is made for these differences, the field sensitivities of Pi(4) and Pi(5) of the two eyes do not differ. The field sensitivities of Pi(4) and Pi(5) of the normal eye, on the other hand, differ significantly from those of the average spectra obtained on four normal trichromats by Stiles, in a way that cannot be attributed to differences in transmittance of ocular media.7. It is concluded that classical (or acquired) tritanopia is not distinguishable in its manifestations from congenital tritanopia; furthermore, tritanopia can be regarded as a reduced form of normal trichromacy, once allowances are made for absorption of the ocular media and for variations among normal trichromats.8. Despite extensive search no evidence could be uncovered which might exclude the hypothesis that the colour vision in tritanopia depends exclusively upon absorption in only two foveal cone pigments, one long-wave-absorbing and one medium-wave-absorbing.

Adult

Perception of colour in unilateral tritanopia.

The unilateral tritanope described in the previous paper (Alpern, Kitahara & Krantz, 1983) was able to match every narrow-band light presented to his tritanopic eye with lights from a tristimulus colorimeter viewed in the adjacent field by the normal eye. In two regions of the spectrum (called isochromes) physically identical lights appeared identical to the observer's two eyes. One isochrome was close to 'blue' for the normal eye, the other was in the long-wave spectral region seen by the normal eye predominantly as 'red'. Between these isochromes the normal eye required less than spectral purity to match, dropping to near zero purity at 560-570 nm. A mixture of the two isochromes that appeared purple to the normal eye appeared neutral to the tritanopic eye. Hence dichoptic matches grossly violate Grassmann's additivity law. For the normal eye colour naming conformed to typical normal results. For the tritanopic eye the results were coherent with those found by dichoptic matching: the spectrum was divided into two regions by the achromatic neutral band. To the short-wave side, only the colour names 'blue' and 'white' were ever used. To the long-wave side the predominant colour names were 'red' and 'white' with some 'yellow'. Spectral lights appeared neither 'red-blue' nor greenish. Surrounding the test with an annulus either 430 nm, 650 nm, or a mixture of these, fails to induce any greenish appearance, although the achromatic band shifted in the expected directions. It is concluded that there must be exactly three functionally independent, essentially non-linear central codes for colour perception, and that these codes are different from those suggested in existing theories of colour perception.

Adaptation, Physiological

The directional sensitivities of the Stiles' colour mechanisms.

Field sensitivities of the three IIj (j = 3, 4, 5) mechanisms of Stiles were measured for monochromatic backgrounds of different wave numbers (mu)-1 traversing the eye through different points (r) displaced along a horizontal chord through the centre of the entrance pupil. Each mechanism shows an insensitivity to the direction of retinal incidence of short-wave backgrounds not previously described. The spectral densities of the centre-most part of the lens and of the macular pigment were measured on this eye. With reasonable assumptions the former allowed for correction at the receptor level of the directional sensitivity; together with the latter it allowed correction for the spectral sensitivity as well. No correction for the attenuation of the high spatial frequencies of the background as it traversed the pupil at different r was needed. The anomalies of section 2 (above) disappear after correction for losses in the eye media. After these corrections, for every mu and r, the results are well described by the parabola 'tentatively' suggested by Stiles (1939) for each mechanism, allowing only a small amount of variance attributable to experimental imprecision alone. Each mechanism is most sensitive to backgrounds going through essentially the same point of the pupil, independent of background. This result is inconsistent with a qualitative explanation of the 'hue shift' suggested by Safir, Hyams & Philpot (1971). The field sensitivity spectra for backgrounds traversing the pupil at this most effective point and at the 3.5 mm margin, are the data needed to predict this observer's brightness and colour matches of monochromatic lights passing through the entrance pupil at these two points according to a unified theory of the two Stiles-Crawford effects. In the following paper these predictions are quantified and confronted with results of the matching experiments (Alpern, Kitahara & Tamaki, 1982).

Adult