Fulminant endocarditis and disseminated infection caused by carbapenem-resistant Acinetobacter baumannii in a renal-pancreas transplant recipient.

Acinetobacter baumannii is an important cause of healthcare-associated infections, and is particularly problematic among patients who undergo organ transplantation. We describe a case of fulminant sepsis caused by carbapenem-resistant A. baumannii harboring the blaOXA-23 carbapenemase gene and belonging to international clone II. This isolate led to the death of a patient 6 days after simultaneous kidney-pancreas transplantation. Autopsy findings revealed acute mitral valve endocarditis, myocarditis, splenic and renal emboli, peritonitis, and pneumonia. This case highlights the severe nature of certain A. baumannii infections and the vulnerability of transplanted patients to the increasingly intractable "high-risk" clones of multidrug-resistant organisms.

Visual sensitivity: significant within-species variations in a nonhuman primate.

Among squirrel monkeys (Saimiri sciureus) there are significant sex-related differences in visual sensitivity. As measured behaviorally in an increment-thershold task, a sample of males was found to be substantially less sensitive to long-wavelength (640-nanometer) light than a group of females tested in the same way, although the two groups showed no significant differences in sensitivity to a middle-wavelength (540-nanometer) light. The two group also differed on a test designed to measure the effects of chromatic adaptation.

Spectral tuning of pigments underlying red-green color vision.

Variations in the absorption spectra of cone photopigments over the spectral range of about 530 to 562 nanometers are a principal cause of individual differences in human color vision and of differences in color vision within and across other primates. To study the molecular basis of these variations, nucleotide sequences were determined for eight primate photopigment genes. The spectral peaks of the pigments specified by these genes spanned the range from 530 to 562 nanometers. Comparisons of the deduced amino acid sequences of these eight pigments suggest that three amino acid substitutions produce the approximately 30-nanometer difference in spectral peaks of the pigments underlying human red-green color vision, and red shifts of specific magnitudes are produced by replacement of nonpolar with hydroxyl-bearing amino acids at each of the three critical positions.

Functional organization of the second cortical visual area in primates.

The functional organization of the second cortical visual area was examined with three different anatomical markers: 2-[14C]deoxy-D-glucose, cytochrome oxidase, and various myelin stains. All three markers revealed strips running throughout the area, parallel to the cortical surface. The boundaries of these strips provide an anatomical criterion for defining the borders of this extrastriate region. Further, the demonstration of these strips allows a functional and anatomical analysis of modules in the area, just as the recent demonstration of spots in the primary visual cortex has allowed an analysis of modules there. The strips differ structurally and functionally from interstrip regions and these differences are similar to those seen between the spots and the interspot regions in the primary visual cortex. In the macaque the strips and spots differ with regard to binocular organization.

Rod photoreceptors and scotopic vision in ground aquirrels.

Ground squirrel retinas contain a relatively small complement of rods (5--10% of all photoreceptors) which are thought to provide the basis for a weak scotopic visual capacity. In a previous investigation of the California ground squirrel (Spermophilus beecheyi) involving the recording of a retinal gross potential, the electroretinogram (ERG), electrophysiological evidence for a viable scotopic signal could be obtained from some, but not all of the ground squirrels examined. To further pursue the possibility that there is a structural/functional discrepancy in the relationship between rod photoreceptors and scotopic vision in the ground squirrel, several experiments involving electrophysiological, behavioral, and anatomical observations have been conducted. We found that although about one-third of the ERGs recorded from a large sample of California ground squirrels lack those characteristics which would indicate the presence of a viable scotopic signal, the retinas of all the squirrels appear to contain the same small population of rod photoreceptors. Additional experiments on the golden-mantled ground squirrel (Spermophilus lateralis), including behavioral as well as ERG measurements and anatomical observations, lead to this same conclusion.

Scotopic and photopic vision in the California ground squirrel: physiological and anatomical evidence.

The California ground squirrel is a highly diurnal species previously thought to have an all-cone retina. This issue was re-examined in physiological and anatomical experiments. The electroretinogram (ERG) was used to measure the spectral sensitivity of the eye under different conditions of adaptation. The occurrence of a Purkinje shift could be demonstrated, although there was some indication that not all members of this species show such a shift. Spectral sensitivity of the dark-adapted eye of this squirrel is close to that predicted by a typical mammalian rhodopsin. Light adaptation produces a shift in spectral sensitivity to a peak location of about 525 nm. It was shown that two mechanisms having different spectral sensitivities contribute to the photopically recorded ERG. The degree to which these two mechanisms contribute to the ERG was found to be strikingly different from the degree to which the two contribute to visual behavior. Our anatomical results indicate that the retina of the California ground squirrel has two structurally distinct photoreceptors which, on the basis of various criteria, can be classified as cone and rod-like. The rod-like receptors comprise about 6-7% of the total. The two photoreceptor types differ in placement of their inner segments, size of their outer segments, outer segment ultrastructure, and terminal structure and organization.

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.

The effects of prolonged dark exposure on visual thresholds in young and adult rats.

A comparison of electroretinogram (ERG) thresholds measured on rats reared in continuous darkness and under cyclic lighting conditions shows that by 30 days of age the dark-reared animals have achieved significantly lower thresholds than the animals reared under cyclic illumination. Ten days of continuous dark exposure produces this same increase in sensitivity in adult rats reared in cyclic lighting. These changes in sensitivity appear to reflect structural changes occurring within the rod outer segments.

Flicker ERG responses to stimuli parametrically modulated in color space.

PURPOSE: To develop methods for recording human electroretinogram (ERG) responses to stimuli that modulate different classes of cones in various ratios, to draw inferences about the combination of cone signal in early retinal processing. METHODS: Subjects viewed large-field temporal modulations presented on a computer-controlled color monitor. A flicker photometric paradigm was used to equate the ERG response elicited by interleaved reference and test modulations. Test modulations were chosen to stimulate the L- and M-cones in various ratios. Results were obtained from color-normal subjects, dichromats, and an anomalous trichromat. RESULTS: Reliable signals were obtained from all subjects to both L- and M-cone-isolating modulations and to intermediate modulations. Signals from color-defective subjects were predominantly determined by the modulation seen by only one cone type, whereas signals from color-normal subjects were sensitive to both L- and M-cone modulations. For most color-normal subjects, the recorded signal was a linear function of the contrasts seen by the L- and M-cones. There was individual variability in how strongly each cone type contributed to the overall signal. CONCLUSIONS: It is straightforward to record signals to color modulations presented on a CRT by using the flicker photometric ERG. For most observers, signals from L- and M-cones combine linearly. The relative contribution of the two cone classes varies across observers, probably because of individual differences in the relative numbers of L- and M-cones.

Retinoid-binding proteins in cone-dominant retinas.

We identified and localized interphotoreceptor (or interstitial) retinoid-binding protein (IRBP) and cellular retinaldehyde-binding protein (CRALBP) in the cone-dominant retinas of diurnal squirrels. Western blots were prepared from sodium dodecyl sulfate polyacrylamide gels (SDS-PAGE) from whole retina, and from retina proximal and distal to the photoreceptor nuclei. Blots were incubated with purified rabbit IgG's specific for the bovine retinal antigens, and the labeled components were visualized using immunoperoxidase techniques. Anti-bovine IRBP and anti-bovine CRALBP recognized single components on gels of retinal supernatants that corresponded to the electrophoretic migration of the bovine antigens. The component recognized by anti-bovine IRBP on blots of outer retinal proteins (Mr 146,000) was absent on blots of inner retinal proteins. Twelve and 24 hr after intravitreal injection of 3H-L-fucose, electropherograms showed one major peak of radioactivity that coincided with the component recognized by anti-bovine IRBP. By immunoelectron microscopy, anti-bovine CRALBP labeling was restricted to the cytoplasm of both RPE and Muller cells, with light labeling of nuclear euchromatin in both cell types. In contrast, anti-bovine IRBP recognized antigenic sites primarily in the interphotoreceptor space (IPS). Intracellular labeling was limited to occasional granules in the photoreceptor myoids and the apical RPE cytoplasm. Extracellular labeling with anti-bovine IRBP was strongly associated with patches or small clumps of amorphous, electron opaque material distributed throughout the IPS. This material was particularly prominent near the cone outer segment plasma membranes, and was tentatively identified as the residual interphotoreceptor matrix that remained after exposure to the solvents used during tissue processing. In general, the results are consistent with those obtained in rod-dominant species. In addition, they imply that cones as well as rods are responsible for IRBP synthesis in the ground squirrel.

Transgenic mice expressing a functional human photopigment.

PURPOSE: Changes in retinal photopigments represent a fundamental step in the evolution of visual systems, in that addition of new pigment types or alterations in the spectral absorption properties of existing pigments modify visual capacities and thus open new visual worlds. To provide a tool that would allow direct examination of the changes caused by the presence of novel photopigments, this study was designed to determine whether a gene encoding a human cone photopigment introduced into the mouse genome would be expressed in a cone-specific manner and would support phototransduction. METHODS: Mice transgenic for the human long wavelength-sensitive (L) photopigment were generated by microinjection of fertilized mouse eggs. RNA expression in different tissues was monitored by reverse transcription-polymerase chain reaction analysis. Photopigment protein was localized in retinal cross sections and wholemounts by antibody staining. Light transduction of the cone photopigments was assessed by flicker photometric electroretinography (ERG). RESULTS: The human transgene was expressed specifically in the mouse cones in quantities comparable to those of the mouse middle wavelength-sensitive (M) pigment gene. Immunocytochemical analysis showed that the human L pigment was abundantly synthesized in most mouse cones, was translocated to the outer segments, and caused no detectable cone degeneration. Electroretinographic spectral sensitivity analysis showed that the human L pigment was efficient in eliciting an electrical response. The degree of expression of the transgene in the two founders correlated well with the spectral responsivity of the ERG. CONCLUSIONS: The human L photopigment transduces light efficiently in mouse cones, implying that all protein domains necessary for efficient interaction with intracellular transport and signal transduction machineries in mouse cones have been conserved through evolution. The expression of the human L photopigment gene in both classes of cone of the mouse retina indicates that the transgene did not have the regulatory elements necessary for restricting its expression to mouse M cones or that such elements are not recognized in mouse UV-sensitive cones.

Photopigments and colour vision in New World monkeys from the family Atelidae.

Most New World monkeys have an X-chromosome opsin gene polymorphism that produces a variety of different colour vision phenotypes. Howler monkeys (Alouatta), one of the four genera in the family Atelidae lack this polymorphism. Instead, they have acquired uniform trichromatic colour vision similar to that of Old World monkeys, apes and people through opsin gene duplication. In order to determine whether closely related monkeys share this arrangement, spectral sensitivity functions that allow inferences about cone pigments were measured for 56 monkeys from two other Atelid genera, spider monkeys (Ateles) and woolly monkeys (Lagothrix). Unlike howler monkeys, both spider and woolly monkeys are polymorphic for their middle- and long-wavelength cone photopigments. However, they also differ from other polymorphic New World monkeys in having two rather than three possible types of middle- and long-wavelength cone pigments. This feature directly influences the relative numbers of dichromatic and trichromatic monkeys.

Uniformity of colour vision in Old World monkeys.

It is often assumed that all Old World monkeys share the same trichromatic colour vision, but the evidence in support of this conclusion is sparse as only a small fraction of all Old World monkey species have been tested. To address this issue, spectral sensitivity functions were measured in animals from eight species of Old World monkey (five cercopithecine species and three colobine species) using a non-invasive electrophysiological technique. Each of the 25 animals examined had spectrally well-separated middle- and long-wavelength cone pigments. Cone pigments maximally sensitive to short wavelengths were also detected, implying the presence of trichromatic colour vision. Direct comparisons of the spectral sensitivity functions of Old World monkeys suggest there are no significant variations in the spectral positions of the cone pigments underlying the trichromatic colour vision of Old World monkeys.

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.

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.

An ultrastructural study of the effects of mefloquine on malaria parasites.

The ultrastructural changes induced by the administration of a recently developed antimalarial drug, mefloquine, were studied in mice infected with Plasmodium berghei and human erythrocytes infected with P. falciparum in vitro. Pronounced changes which occurred in both experiments comprised swelling of the parasites' food vacuoles with gradual loss of pigment granules, which did not form clumps as occurs with chloroquine. These findings suggest that the malarial parasites' food vacuole is the target of this drug.

Ultrastructural study of the effects of chloroquine and verapamil on Plasmodium falciparum.

Verapamil, a calcium antagonist, has recently been shown to reverse chloroquine resistance in malarial parasites in vitro. We report the first ultrastructural morphological changes associated with this phenomenon using chloroquine-sensitive and -resistant clones of Plasmodium falciparum. While the administration of 6.3 x 10(-8) M chloroquine had little morphological effect on the chloroquine-resistant strain, the combination of chloroquine and verapamil resulted in typical chloroquine-related food vacuolar swelling with increased amounts of granular matrix. Secondary morphological changes included degeneration of nuclei, mitochondria, and other organelles. These effects appeared similar to those in the chloroquine-sensitive strain of P. falciparum treated with chloroquine alone or with the chloroquine/verapamil combination. Furthermore mild food vacuolar changes were seen in a small number of parasites (from both chloroquine-sensitive and -resistant groups) exposed to high concentrations (1 x 10(-4) M) of verapamil alone.

Prospects for trichromatic color vision in male Cebus monkeys.

Polymorphic color vision is characteristic of many species of New World monkey. A fundamental feature of the polymorphism is that male monkeys are routinely dichromatic. A recent paper describes an experiment in which Cebus monkeys were required to discriminate between pairs of Munsell color chips (Pessoa VF, Tavares MCH, Aguiar L, Gomes UR, Tomaz C. Color vision discrimination in the capuchin monkey Cebus apella: evidence for trichromaticity. Behav Brain Res 1997;89:285-288). The results were interpreted as demonstrating trichromatic color vision in male Cebus monkeys. An examination of the literature on Cebus. monkey photopigments and results from a replication of the discrimination experiment conducted with dichromatic human subjects cast doubt on this claim.

Action spectrum of the retinal mechanism mediating nocturnal light-induced suppression of rat pineal gland N-acetyltransferase.

The spectral properties of the retinal mechanism mediating the inhibitory effects of nocturnal light on pineal gland N-acetyltransferase (NAT) activity were determined. Pineal gland NAT activity declined linearly in albino rats exposed to different irradiances of a 460 or 580 nm monochromatic light during the middle of the dark phase of the cycle. The difference in sensitivity to the test lights is that predicted for a photopigment having peak absorbance at 495 nm, suggesting the inhibition of pineal gland N-acetyltransferase activity is mediated by the photopigment found in rat rods.