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Biomedical subjects

G H Jacobs

Publications and source records attributed to G H Jacobs.

At least 19 recordsLinked to original sources
PubMed1994

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↗
PubMed1992

Determination of the base recognition positions of zinc fingers from sequence analysis.

The CC/HH zinc finger is a small independently folded DNA recognition motif found in many eukaryotic proteins, which ligates zinc through two cysteine and two histidine ligands. A database of 1340 zinc fingers from 221 proteins has been constructed and a program for analysis of aligned sequences written. This paper describes sequence analysis aimed at determining the amino acid positions that recognize the DNA bases, by comparing two types of sequence variation. Using the idea that long runs of adjacent zinc fingers have arisen from internal gene duplication, the conservation of each position of the finger within the runs was calculated. The conservation of each position of the finger between homologous proteins from different species was also noted. A correlation of the two types of conservation showed clusters of related amino acids. One cluster of three positions was found to be especially variable within long runs, but highly conserved between corresponding fingers of homologous proteins; these positions are predicted to be the base contact positions. They match the amino acid positions that contact the bases in the co-crystal structure determined by Pavletich and Pabo [Science, 240, 809-817 (1991)]. An adjacent cluster of four positions on the plot may also be associated with DNA binding. This analysis shows that the base recognition positions can be identified even in the absence of a known structure for a zinc finger. These results are applicable to zinc fingers where the structure of the complex is unknown, in particular suggesting that the individual finger--DNA interaction seen in the Zif268--DNA structure has been conserved in many zinc finger--DNA interactions.

Amino Acid Sequence↗
PubMed1992

Cone photopigments in nocturnal and diurnal procyonids.

Procyonids are small, New World carnivores distributed among some 6 genera. Electroretinogram (ERG) flicker photometry was used to measure the spectra of the cone photopigments for members of two nocturnal species, the raccoon (Procyon lotor) and the kinkajou (Potos flavus), and a diurnal species, the coati (Nasua nasua). Each of the 3 has a class of cone photopigment with maximum sensitivity in the middle to long wavelengths. The spectral positioning of this cone is different for the three. Whereas the raccoon and kinkajou are monochromatic, the diurnal coati is a dichromat having an additional class of cone photopigment with peak sensitivity close to 433 nm.

Animals↗
PubMed1992

Experimental IgA-IgG nephropathy induced by a viral respiratory pathogen. Dependence on antigen form and immune status.

BACKGROUND: The etiology of IgA nephropathy (IgAN), the most common form of glomerulonephritis in the world, remains an enigma. Episodes of nephritis are frequently preceded by acute viral respiratory syndromes, but few experimental models associated with acute viral infection exist. EXPERIMENTAL DESIGN: An animal model of IgAN involving Sendai virus, a rodent parainfluenza virus similar to many human respiratory viruses, is described. Mice were either naturally infected or chronically mucosally immunized with virus. Immunized mice were then challenged intravenously with various physical forms of antigen to simulate viremia or antigenemia secondary to acute viral exposure. Twenty-four hours after challenge of immunized mice or 10 days after natural infection, mice were sacrificed. Anti-viral antibody titers, glomerular immune deposits, and glomerular function were evaluated. RESULTS: Chronic mucosal immunization of mice with Sendai virus resulted in a vigorous serum IgA (and IgG) anti-viral immune response, associated with comparable degrees of IgA, IgG, IgM, and antigen deposits in the glomeruli of both challenged and unchallenged mice. Only immunized, challenged mice developed significant proteinuria and hematuria. Neither deposits nor glomerular dysfunction was seen in controls. The physical form of antigen was important for altered glomerular function; although immunized mice challenged with either live or dead virions had a high incidence of hematuria, mice challenged with purified viral glycoproteins did not, even though all mice exhibited comparable immune deposits. Significant deposits of C3 were not present and were not required for glomerular injury. Finally, naturally infected mice exhibited a milder form of IgAN without hematuria. CONCLUSIONS: The experimental conditions for acute exposure to a natural viral respiratory pathogen of mice leading to IgAN are described. This model may be useful both to probe infection-related IgAN, and to facilitate the understanding of the various mechanisms responsible for IgAN.

Animals↗
PubMed1991

Retinal receptors in rodents maximally sensitive to ultraviolet light.

High sensitivity to near-ultraviolet light is a fundamental feature of vision in many invertebrates. Among vertebrates there are some amphibians, birds and fishes that are also sensitive to near-ultraviolet wavelengths. This sensitivity can be achieved through a class of cone photoreceptor containing an ultraviolet-sensitive pigment. Although these receptors were thought not to exist in the eyes of mammals, we now report that some rodents have a retinal mechanism that is maximally sensitive to ultraviolet light.

Animals↗
PubMed1991

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.

Amino Acid Sequence↗
PubMed1991

Behavioral and electrophysiological sensitivity to temporally modulated visual stimuli in the ground squirrel.

Behavioral and electrophysiological methods were used to measure sensitivity to flickering lights in a dichromatic species, the California ground squirrel (Spermophilus beecheyi). Discrimination tests were used to determine spectral sensitivity at stimulus frequencies from 5-50 Hz and increment threshold spectral sensitivity. The contributions of retinal mechanisms to these capacities were assessed by recording the responses of optic nerve fibers to temporally modulated monochromatic lights. In the ground squirrel, as in the human, the shape of the spectral-sensitivity function depends on the temporal frequency of the stimulus. Results from single-unit recording show that all of the classes of optic nerve fibers in the ground squirrel are highly phase-locked to the stimulus for modulation rates as high as 50 Hz. Neither the responses of photoreceptors nor any class of optic nerve fiber can singly account for the behavioral results. The electrophysiological results are also counter to models which propose that temporally dependent changes in the spectral sensitivity of spectrally opponent fibers account for the behavior. The temporal resolution of the optic nerve fibers exceeds that of the behaving animal suggesting that retinal mechanisms do not limit behavioral temporal resolution.

Animals↗
PubMed1990

Polymorphism in normal human color vision and its mechanism.

Earlier we reported that Rayleigh matches made by males with normal color vision fall into distinct groups, and proposed that this behavior reflects an X-chromosome linked polymorphism in the spectral positioning of cone pigments (Neitz & Jacobs, 1986). In the present experiments two different color matches were obtained from each of 60 color normal males. Comparisons of the data from these two matches allowed variations in color matching that are produced by individual differences in the spectral positioning of middle and long wavelength cone pigments to be distinguished from color vision variations caused by other factors. Considered together with findings from molecular biology and spectral measurements of individual cone pigments, these results suggest that among color normal humans: (1) there are discrete variations in both middle and long wavelength cone pigments, and (2) most individuals have more than three different cone pigment types.

Color Perception↗
PubMed1990

Discrimination of luminance and chromaticity differences by dichromatic and trichromatic monkeys.

Dichromatic and trichromatic representatives from two genera of platyrrhine monkeys that show widespread color vision polymorphism (Saguinus--tamarins, Saimiri--squirrel monkeys) were tested for their abilities to make increment-threshold and flicker discriminations based on luminance and chromaticity differences. The details of these tests were arranged to attempt to emphasize the relative contributions to visual behavior of non-opponent and spectrally-opponent neural mechanisms. The results indicate that dichromatic and trichromatic monkeys differ only trivially on tests where performance is based on the contributions of non-opponent mechanisms, that the contribution of spectrally opponent mechanisms to the "brightness signal" is very similar in trichromatic and dichromatic monkeys, and that in increment-threshold discriminations where there are both chromaticity and luminance cues some test wavelengths yield superior performance for trichromats while others appear to favor the dichromat.

Animals↗
PubMed1990

Localized fibrous tumors of the pleura: correlation of histopathological, immunohistochemical and ultrastructural features.

The histogenesis of localized fibrous tumor of the pleura (LFTP) is controversial. We studied 12 LFTP's by light microscopy; by immunohistochemical staining for cytokeratin (CK), vimentin, muscle-specific actin, desmin, S-100 protein, epithelial membrane antigen (EMA) and factor VIII; by electron microscopy in 6 tumors; and by lung digestion for asbestos bodies in 4 cases. Three histologic patterns occurred in combination: 1) collagenous, 2) cellular and 3) hypocellular/myxoid. Hemangiopericytoma-like foci were prominent in the cellular areas of 9 tumors. Unusual features included diffuse small cells in 3 tumors, microcystic foci in 2, macrocystic areas in 5 and tumor giant cells in 4 tumors. Neoplastic cells in all patterns stained positively for vimentin and actin in 9 and 4 tumors, respectively, and were negative for all other markers. CK and EMA were identified in mesothelial and epithelial invaginations only. Ultrastructurally, neoplastic cells demonstrated intercellular junctions, intermediate or thin filaments, dense bodies and rough endoplasmic reticulum. Basal lamina was focally present in 5 tumors, while tonofilaments, desmosomes and short microvilli were observed in one case. Our results support the conclusion that LFTP is a neoplasm of the multipotential subserosal cell, and usually expresses mesenchymal (fibroblastic/myofibroblastic) differentiation. Coexpression of mesothelial features is rare. Lung asbestos body quantitation in 4 patients suggests that there is no association between LFTP and asbestos exposure.

Actins↗
PubMed1990

Duplicity theory and ground squirrels: linkages between photoreceptors and visual function.

The presence of rod and cone photoreceptors has traditionally been linked to well-defined classes of visual capacity by the generalization known as duplicity theory. This paper summarizes results obtained from studies of vision and the visual system in ground squirrels (Spermophilus sp.) that reveal instances where structure/function linkages depart from expectations based in duplicity theory. The details of these exceptions are reviewed and their possible mechanisms discussed.

Animals↗
PubMed1989

Analysis of fusion gene and encoded photopigment of colour-blind humans.

In humans, long-wavelength-sensitive and middle-wavelength-sensitive cone pigments are encoded by genes lying in a head-to-tail tandem array on the X chromosome. Deficiencies in red-green colour vision seem to arise from unequal recombination of these normal X-linked genes. In some dichromats this recombination is believed to yield a fusion gene encoding a product with an absorption spectrum similar to that of one or the other of the normal photopigments. Until now, however, such a relationship between the structure of a pigment gene and the spectral properties of its encoded pigment has not been directly shown. We have now sequenced a fusion gene isolated from a red-green colour-blind human and determined the spectral properties of the pigment that it encodes. The absorption spectrum of the photopigment was very similar to that of normal middle-wavelength-sensitive photopigment, even though about half of its DNA coding sequence seems to be derived from a gene encoding normal long-wavelength-sensitive pigment. These results indicate the regions of the X-encoded photopigment apoproteins that are responsible for differences in their spectral tuning, and imply that the striking variations in colour vision among anomalous trichromats of a particular type are not attributable to anomalous pigments with differing spectral peaks.

Adult↗
PubMed1989

Cone monochromacy and a reversed Purkinje shift in the gerbil.

Retinal spectral sensitivity of the gerbil (Meriones unguiculatus) shows that this animal has a unique photoreceptor complement: there is only a single class of cone and the spectrum for these receptors is peak shifted toward the short wavelengths relative to the spectra obtained from rods.

Animals↗
PubMed1989

Color vision in the dog.

The color vision of three domestic dogs was examined in a series of behavioral discrimination experiments. Measurements of increment-threshold spectral sensitivity functions and direct tests of color matching indicate that the dog retina contains two classes of cone photopigment. These two pigments are computed to have spectral peaks of about 429 nm and 555 nm. The results of the color vision tests are all consistent with the conclusion that dogs have dichromatic color vision.

Animals↗
PubMed1989

Spectral sensitivity of cones in an ungulate.

Ungulates have been classified as having arrhythmic eyes in the sense that they contain features appropriate both to diurnal and nocturnal life. The former is typically associated with multiple classes of cones and a color-vision capacity. To see if an arrhythmic animal has these features, the number of cone classes was determined and the spectra of these cones were measured in a common ungulate, the domestic pig (Sus scrofa). Examination with electroretinogram (ERG) flicker photometry revealed the presence of two classes of cones in the pig's eye having average maximum sensitivity (lambda max) at 439 nm and 556 nm, respectively. This ungulate thus has the requisite retinal basis for dichromatic color vision.

Animals↗
PubMed1988

Spectral mechanisms in the tree squirrel retina.

The retina of the gray squirrel (Sciurus carolinensis) contains rods and cones in a ratio of about 2:3. The spectral mechanisms in this retina were examined in behavioral and electrophysiological experiments. Tests of color vision revealed that this animal has a spectral neutral point at about 500 nm and, thus, dichromatic color vision. Recordings made from single optic nerve fibers and results obtained from an analysis of the flicker photometric electroretinogram (ERG) indicated that vision in the gray squirrel is based on three spectral mechanisms. One of these, presumably rod-based, has peak sensitivity at about 502 nm. The other two mechanisms reflect the presence of two classes of cone having average peak sensitivity of about 444 nm and 543 nm.

Animals↗
PubMed1988

Temporal properties of the short-wavelength cone mechanism: comparison of receptor and postreceptor signals in the ground squirrel.

Temporal properties of the short-wavelength cone mechanism of the California ground squirrel (Spermophilus beecheyi), a dichromat, were explored with single light pulses and pulse trains. Both the electroretinogram (ERG) and the isolated PIII component of the retinal gross response were recorded under chromatic adaptation conditions that favored the detection of test lights by either the middle-wavelength mechanism or the short-wavelength mechanism. The ERG b-wave generated by the short-wavelength mechanism was significantly slower than that of the middle-wavelength mechanism, but there was no such difference in the PIII components of the two mechanisms. Analysis of PIII revealed that both cone types respond equally well to flicker at rates at least as high as 46 Hz. Differences in the temporal response properties of these two cone mechanisms must arise largely from post-receptoral interactions.

Action Potentials↗