Photopigments and seeing--lessons from natural experiments: the Proctor lecture.
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Animals↗
Biomedical subjects
G H Jacobs
Publications and source records attributed to G H Jacobs.
Multifocal hepatic lesions in AIDS: an unusual presentation of steatosis.
Patients infected with HIV frequently have abnormal results on liver tests, leading to radiographic evaluation for hepatic lesions. The etiology of these lesions in patients infected with HIV is most often secondary to infections or tumors. Occasionally, focal abnormalities in the liver are identified in asymptomatic patients. The etiology and clinical course in this subset of patients are not known. However, because of concerns of tumor, an evaluation is usually warranted. We report an unusual case of multifocal hepatic steatosis presenting as multiple liver lesions in an HIV-positive patient with cutaneous Kaposi's sarcoma. This case emphasizes the importance of obtaining a tissue diagnosis in this patient population.
Acquired Immunodeficiency Syndrome↗
Trichromatic colour vision in New World monkeys.
Trichromatic colour vision depends on the presence of three types of cone photopigment. Trichromacy is the norm for all Old World monkeys, apes and humans, but in several genera of New World monkeys, colour vision is strikingly polymorphic. The difference in colour vision between these New and Old World primates results form differing arrangements of the pigment genes on the X chromosome. In Old World primates the three photopigments required for routine trichromatic colour vision are encoded by two or more X-chromosome pigment genes and an autosomal pigment gene. New World monkeys typically have only one X-chromosome pigment gene; multiple alleles allow different types of dichromatic colour vision and, in female heterozygous at this locus, variant forms of trichromatic colour vision. Here we report that multiple X-chromosome pigment genes and trichromatic colour vision are the norm for one genus of platyrrhine monkey, the howler monkey, Alouatta.
Alouatta↗
Mutations in S-cone pigment genes and the absence of colour vision in two species of nocturnal primate.
Most primates have short-wavelength sensitive (S) cones and one or more types of cone maximally sensitive in the middle to long wavelengths (M/L cones). These multiple cone types provide the basis for colour vision. Earlier experiments established that two species of noctural primate, the owl monkey (Aotus trivirgatus) and the bushbaby (Otolemur crassicaudatus), lack a viable population of S cones. Because the retinas of these species have only a single type of M/L cone, they lack colour vision. Both of these species have an S-cone pigment gene that is highly homologous to the human S-cone pigment gene. Examination of the nucleotide sequences of the S-cone pigment genes reveals that each species has deleterious mutational changes: in comparison to the sequence for the corresponding region of the human gene, exon 4 of the bushbaby S-cone pigment gene has a two nucleotide deletion and a single nucleotide insertion that produces a frame shift and results in the introduction of a stop codon. Exon 1 of the owl monkey S-cone pigment gene likewise contains deletions and insertions that produce a stop codon. The absence of colour vision in both of these nocturnal primates can thus be traced to defects in their S-cone pigment genes.
Amino Acid Sequence↗
Primate photopigments and primate color vision.
The past 15 years have brought much progress in our understanding of several basic features of primate color vision. There has been particular success in cataloging the spectral properties of the cone photopigments found in retinas of a number of primate species and in elucidating the relationship between cone opsin genes and their photopigment products. Direct studies of color vision show that there are several modal patterns of color vision among groupings of primates: (i) Old World monkeys, apes, and humans all enjoy trichromatic color vision, although the former two groups do not seem prone to the polymorphic variations in color vision that are characteristic of people; (ii) most species of New World monkeys are highly polymorphic, with individual animals having any of several types of dichromatic or trichromatic color vision; (iii) less is known about color vision in prosimians, but evidence suggests that at least some diurnal species have dichromatic color vision; and (iv) some nocturnal primates may lack color vision completely. In many cases the photopigments and photopigment gene arrangements underlying these patterns have been revealed and, as a result, hints are emerging about the evolution of color vision among the primates.
Animals↗
ERG measurements of the spectral sensitivity of common chimpanzee (Pan troglodytes).
The spectral sensitivity of the common chimpanzee (Pan troglodytes) was measured with electroretinogram (ERG) flicker photometry. Chromatic adaptation conditions were used to establish the presence of S-, M- and L-cone pigments. Each of 26 chimpanzees showed substantial and approximately equivalent adaptational changes over the middle and long wavelengths implying an absence of any significant polymorphic variations in the M- and L-cone pigments. As inferred from ERG measurements, the S-cone pigment of the chimpanzee has a spectral peak of about 430 nm. Chimpanzee spectral sensitivity measurements were compared to those obtained from equivalently tested normal human trichromats. The spectral sensitivity of the two species is very similar, chimpanzees being slightly more sensitive to short wavelength lights and slightly less sensitive to long wavelength lights than human subjects. Curve-fitting analyses suggest that spectral filtering may be lower in the chimpanzee lens than it is in the human lens, and that the L/M cone ratio is lower in the chimpanzee.
Adaptation, Ocular↗
Electroretinogram flicker photometry and its applications.
The electroretinogram (ERG) has been a traditional tool for the measurement and the analysis of spectral sensitivity. With the appropriate choices of stimulus and measurement conditions, the ERG permits a noninvasive examination of photopigment complement and provides the means for studying the combination of spectral signals at various locations throughout the retina. There are a number of practical problems associated with making spectral measurements with the ERG. One approach to minimizing these problems is to exploit the advantages of a flicker-photometric procedure. We summarize a method used to conduct ERG flicker photometry and illustrate a range of problems to which this technique can be successfully applied.
Electroretinography↗
Genetic basis of photopigment variations in human dichromats.
The spectral sensitivities of the X-encoded pigments in dichromats were studied using the electroretinogram. The action spectra measured for these subjects correspond to four distinctly different X-encoded visual pigments, two different middle-wave pigments spectrally separated by 7 nm and two different long-wave pigments separated by 5 nm. Amino acid sequences were deduced from examination of the genes encoding the pigments. Pairwise comparisons of the opsin structures and pigment spectra confirm and clarify earlier conclusions. Substitutions in exon 5 of the genes produce the spectral difference that separates human X-encoded pigments into middle- and long-wave classes. Polymorphisms in exons 2-4 produce subtypes of pigments that fall within those major classes. Substitution of half of a middle-wave gene with long-wave sequence (exons 1-3) does not shift the middle-wave spectrum. Combined substitutions at positions 230, 233 and 180 produce a 7 nm shift in the in the middle-wave pigment spectrum. Two subtypes of long-wave pigments that differ in the presence of serine or alanine at position 180 and occur in dichromats, deuteranomalous trichromats, and color normals are spectrally separated by 5-7 nm.
Adolescent↗
Electrophysiological measurements of spectral mechanisms in the retinas of two cervids: white-tailed deer (Odocoileus virginianus) and fallow deer (Dama dama).
Electroretinogram (ERG) flicker photometry was used to study the spectral mechanisms in the retinas of white-tailed deer (Odocoileus virginianus) and fallow deer (Dama dama). In addition to having a rod pigment with maximum sensitivity (lambda max) of about 497 nm, both species appear to have two classes of photopic receptors. They share in common a short-wavelength-sensitive cone mechanism having lambda max in the region of 450-460 nm. Each also has a cone having peak sensitivity in the middle wavelengths, but these differ slightly for the two species. In white-tailed deer the lambda max of this cone is about 537 nm; for the fallow deer the average lambda max value for this mechanism was 542 nm. Deer resemble other ungulates and many other types of mammal in having two classes of cone pigment and, thus, the requisite retinal basis for dichromatic color vision.
Animals↗
Effect of corticosteroid therapy on human immunodeficiency virus-associated nephropathy.
PURPOSE: Human immunodeficiency virus-associated nephropathy (HIV-AN) occurs predominantly in blacks and is characterized histologically by focal segmental glomerulosclerosis or mesangial proliferation and a lymphohistiocytic tubulointerstitial infiltrate. Patients manifest heavy proteinuria and, once azotemia occurs, progress rapidly to end-stage renal disease within 2 to 6 months. No treatment has been shown to be useful for HIV-AN. The purpose of this study was to determine the effect of corticosteroid agents on the progression of HIV-AN. PATIENTS AND METHODS: Four consecutive HIV-infected adults with fewer than 200 CD4 cells/microL, moderate to severe renal insufficiency, proteinuria greater than 2 g per 24 hours, and HIV-AN demonstrated by renal biopsy were treated with 60 mg of prednisone daily for 2 to 6 weeks. Patients were followed with respect to serum creatinine level, 24-hour protein excretion, adverse drug reactions, and the occurrence of opportunistic infections. RESULTS: CD4 counts ranged from 30 to 80 cells/microL before therapy with steroids. The mean (+/- SD) pretreatment serum creatine concentration was 9.1 +/- 5.7 mg/dL and decreased to 3.3 +/- 1.8 mg/dL (P < 0.05) after 2 to 6 weeks of corticosteroid therapy. Twenty-four hour protein excretion did not change (5.2 +/- 2.4 g pretreatment versus 4.6 +/- 4.1 g posttreatment). One patient was able to discontinue dialysis after 10 days. Two patients developed Mycobacterium avium-complex infections and steroid-associated psychosis. One of these patients developed a recurrence of genital herpes, and the other developed dermatomal zoster. None of the four required dialysis during a 1.5- to 5.5-month period of follow-up after cessation of steroid treatment. CONCLUSION: In selected patients with HIV-AN, short-term treatment with corticosteroid agents improves renal function and prevents the development of end-stage renal disease during a 1.5- to 5.5-month period of observation, but may be associated with an increased risk of opportunistic infection.
Adult↗
Central nervous system Whipple's disease: relapse during therapy with trimethoprim-sulfamethoxazole and remission with cefixime.
The central nervous system (CNS) is frequently involved in patients with Whipple's disease and is the most common site of disease relapse. Antibiotics such as trimethoprim-sulfamethoxazole (TMP-SMX) that have reliable CNS penetration, are therefore recommended as first-line therapy. We report a patient with Whipple's disease who was treated with TMP-SMX and presented 14 months after initiation of therapy with visual decline and severe headaches. The patient was also treated concurrently with low-dose weekly methotrexate for severe psoriasis. Evaluation by magnetic resonance imaging revealed bilateral posterior white matter abnormalities that pathologically were consistent with Whipple's disease. He was ultimately treated with cefixime, an orally administered third-generation cephalosporin. Visual function improved on this regimen and follow-up magnetic resonance imaging showed regression of the lesions. This case represents the first report of both CNS relapse during therapy with TMP-SMX and successful treatment with cefixime. We also speculate that methotrexate, which impairs cell-mediated immunity, may have contributed to the relapse.
Cefixime↗
Sensitivity to ultraviolet light in the gerbil (Meriones unguiculatus): characteristics and mechanisms.
In earlier electrophysiological experiments on the Mongolian gerbil (Meriones unguiculatus) evidence was obtained to suggest that the retina of this rodent contains only a single type of cone. The cones were found to have peak sensitivity of about 493 nm. Gerbil rods have peak sensitivity of about 500 nm, yielding a Purkinje shift that is small in magnitude and reversed in direction from that conventionally found among mammals. In a series of experiments we extended electrophysiological and behavioral measurements to include UV stimulation and this reveals a second photopic mechanism. Several pieces of evidence suggest this second mechanism is a cone having peak sensitivity of about 360 nm. Results from adaptation experiments show that the sensitivities of the two cone mechanisms can be independently manipulated, and thus they presumably reflect the operation of two types of cone photopigment. The results from behavioral experiments verify that the gerbil UV mechanism provides information that can be used to make visual discriminations based on intensity differences. A test of color vision additionally suggests that the two cone pigments can support some color discriminations.
Adaptation, Ocular↗
Quinine-associated acute interstitial nephritis.
Quinine-induced acute renal failure attributed to the hemolytic-uremic syndrome has been infrequently reported. A case of acute renal failure due to acute interstitial nephritis associated with ingestion of quinine and the subsequent response to steroid therapy is described.
Acute Disease↗
Spectral sensitivity, photopigments, and color vision in the guinea pig (Cavia porcellus).
Behavioral discrimination tests and electroretinogram (ERG) flicker photometry were used to measure spectral sensitivity and to define the spectral mechanisms of the guinea pig (Cavia porcellus). Results from these 2 approaches converge to indicate that guinea pig retinas contain rods with peak sensitivity of about 494 nm and 2 classes of cone having peak sensitivities of about 429 nm and 529 nm. The presence of 2 classes of cones suggests a retinal basis for a color vision capacity. Behavioral tests of color vision were conducted that verified this prediction: Guinea pigs have dichromatic color vision with a spectral neutral point centered at about 480 nm. The cone pigment complement of the guinea pig is different from that known to characterize other rodents.
Animals↗
On the identity of the cone types of the rat retina.
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Animals↗
More than three different cone pigments among people with normal color vision.
A fundamental feature of normal color vision is that red and green lights can be mixed to appear identical with a monochromatic yellow light. Another characteristic of normal color vision is that people often disagree on the amounts of red and green needed in the mixture to exactly match the yellow. Comparison of such color vision differences with photopigment gene differences reveals that a serine/alanine polymorphism at amino acid position 180 of X-encoded pigments can account for this type of color vision variation. This amino acid change shifts the spectrum of the pigment produced by about 6 nm, a value that would predict a larger minimum color vision difference between individuals than is actually observed. This discrepancy can be explained if, counter to the Young-Helmholtz theory as the explanation of trichromacy, many people with normal color vision have more than three spectrally different cone pigments.
Base Sequence↗
Genetic basis of polymorphism in the color vision of platyrrhine monkeys.
It was earlier proposed that the polymorphism of color vision observed in some neotropical monkeys could be accounted for by assuming that these animals have only a single photopigment gene locus on the X-chromosome. Three kinds of evidence have been added to existing data sets in an effort to evaluate the adequacy of the single locus model: (1) photopigment complements of squirrel monkeys (Saimiri sciureus) have been determined using electroretinogram flicker photometry; (2) photopigment pedigrees have been established for several families of squirrel monkey; (3) X-chromosome pigment genes obtained from six dichromatic monkeys (three squirrel monkeys; three tamarins--Saguinus fuscicollis) have been examined to search for sequence polymorphisms at those gene loci believed crucial for spectral tuning. All of these results are in accord with the idea that some species of platyrrhine primate have only a single type of photopigment gene on the X-chromosome.
Animals↗
Photopigments and color vision in the nocturnal monkey, Aotus.
The owl monkey (Aotus trivirgatus) is the only nocturnal monkey. The photopigments of Aotus and the relationship between these photopigments and visual discrimination were examined through (1) an analysis of the flicker photometric electroretinogram (ERG), (2) psychophysical tests of visual sensitivity and color vision, and (3) a search for the presence of the photopigment gene necessary for the production of a short-wavelength sensitive (SWS) photopigment. Both electrophysiological and behavioral measurements indicate that in addition to a rod photopigment the retina of this primate contains only one other photopigment type--a cone pigment having a spectral peak ca 543 nm. Earlier results that suggested these monkeys can make crude color discriminations are interpreted as probably resulting from the joint exploitation of signals from rods and cones. Although Aotus has no functional SWS photopigment, hybridization analysis shows that Aotus has a pigment gene that is highly homologous to the human SWS photopigment gene.
Animals↗