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Biomedical subjects

F Horn

Publications and source records attributed to F Horn.

At least 73 records · Page 4Linked to original sources
PubMed1994

The interleukin-6-activated acute-phase response factor is antigenically and functionally related to members of the signal transducer and activator of transcription (STAT) family.

Interleukin-6 (IL-6), leukemia inhibitory factor, oncostatin M, IL-11, and ciliary neurotropic factor are a family of cytokines and neuronal differentiation factors which bind to composite plasma membrane receptors sharing the signal transducing subunit gp130. We have shown recently that IL-6 and leukemia inhibitory factor rapidly activate a latent cytoplasmic transcription factor, acute-phase response factor (APRF), by tyrosine phosphorylation, which then binds to IL-6 response elements of various IL-6 target genes. Here we demonstrate that APRF is activated by all cytokines acting through gp130 and is detected in a wide variety of cell types, indicating a central role of this transcription factor in gp130-mediated signaling. APRF activation is also observed in vitro upon addition of IL-6 to cell homogenates. Protein tyrosine kinase inhibitors block both the tyrosine phosphorylation and DNA binding of APRF. The factor was purified to homogeneity from rat liver and shown to consist of a single 87-kDa polypeptide, while two forms (89 and 87 kDa) are isolated from human hepatoma cells. As reported earlier, the binding sequence specificity of APRF is shared by gamma interferon (IFN-gamma) activation factor, which is formed by the Stat91 protein. Partial amino acid sequence obtained from purified rat APRF demonstrated that it is likely to be related to Stat91. In fact, an antiserum raised against the amino-terminal portion of Stat91 cross-reacted with APRF, suggesting the relatedness of APRF and Stat91. Altogether, these data indicate that APRF belongs to a growing family of Stat-related proteins and that IFN-gamma and IL-6 use similar signaling pathways to activate IFN-gamma activation factor and APRF, respectively.

3T3 Cells↗
PubMed1994

Scotopic threshold response and scotopic PII in glaucoma.

PURPOSE: The value of the ERG scotopic threshold response (STR), which is known to originate in the proximal retina and of the near-threshold scotopic PII(B-wave), was studied in glaucoma. METHODS: Full-field single flashes were presented under scotopic conditions in two subject groups, a glaucoma group (n = 30) and a normal control group (n = 35). The intensity level for evoking STR was where the maximum response occurs, whereas the intensity level for evoking scotopic PII was where the response begins to appear. RESULTS: The STR is only slightly reduced in glaucoma (P = 0.046), but scotopic PII is significantly diminished (P < 0.0001). CONCLUSIONS: The relatively intact STR in glaucoma suggests that structures responsible for its generation are less damaged in glaucoma than those responsible for scotopic PII.

Dark Adaptation↗
PubMed1993

Utility of the color pattern-electroretinogram (PERG) in glaucoma.

Pattern-onset electroretinograms (PERGs) with red-green color contrast (CC) and green-"black" luminance contrast (LC) stripe patterns (0.3 c/deg) were recorded in a group of 80 control subjects and in a group of 42 patients having glaucomas of varying etiology and severity. The PERG data were correlated with the results of static perimetry and optic disc morphometry. In the glaucoma group the PERG was reduced significantly and by relatively similar amounts with both CC and LC stimuli. A significant correlation of the PERG reduction with visual field loss was found only with the CC, not with the LC PERG. Correlations between PERG amplitudes and neuroretinal rim areas of the optic disk were similar for the LC and for the CC stimulus. The rather poor percentage of correct classification of controls and patients based on the PERG or the optic disc morphometry alone can be improved by two-dimensional discriminant analysis using both CC PERG and papillometry data.

Color Perception↗
PubMed1993

[Simple rapid contrast sensitivity test in diagnosis of glaucoma].

BACKGROUND: Psychophysical tests employing high-frequency stimuli are becoming of increasing value in glaucoma diagnosis. In the present study a simple, quick, and sensitive flicker test is described which can be used as an screening examination for glaucoma. METHOD: A flicker test is described which uses a white sinusoidally flickering light presented at 37.1 Hz in a ganzfeld bowl under photopic conditions (ca 10 cd/m2. Fication is not necessary. The modulation (temporal contrast) of the flicker light is varied in small steps until flicker threshold is reached. The reciprocal of the threshold value represents the temporal contrast sensitivity. The test takes only about 5 min per eye. RESULTS: 69 eyes of 69 normals, 60 eyes of 60 ocular hypertensive (OHT), and 50 eyes of 50 patients with primary open angle glaucoma were statistically evaluated. The validation of the sensitivity in both eyes was 75.6% and the specificity was 85.9%. 41.7% of the OHT patients were classified as pathologic. CONCLUSIONS: Thus, the ganzfeld flicker test is a simple and quick (5 min) additional screening test in glaucoma.

Adult↗
PubMed1993

Acute-phase response factor, a nuclear factor binding to acute-phase response elements, is rapidly activated by interleukin-6 at the posttranslational level.

Interleukin-6 (IL-6) is known to be a major mediator of the acute-phase response in liver. We show here that IL-6 triggers the rapid activation of a nuclear factor, termed acute-phase response factor (APRF), both in rat liver in vivo and in human hepatoma (HepG2) cells in vitro. APRF bound to IL-6 response elements in the 5'-flanking regions of various acute-phase protein genes (e.g., the alpha 2-macroglobulin, fibrinogen, and alpha 1-acid glycoprotein genes). These elements contain a characteristic hexanucleotide motif, CTGGGA, known to be required for the IL-6 responsiveness of these genes. Analysis of the binding specificity of APRF revealed that it is different from NF-IL6 and NF-kappa B, transcription factors known to be regulated by cytokines and involved in the transcriptional regulation of acute-phase protein genes. In HepG2 cells, activation of APRF was observed within minutes after stimulation with IL-6 or leukemia-inhibitory factor and did not require ongoing protein synthesis. Therefore, a preexisting inactive form of APRF is activated by a posttranslational mechanism. We present evidence that this activation occurs in the cytoplasm and that a phosphorylation is involved. These results lead to the conclusions that APRF is an immediate target of the IL-6 signalling cascade and is likely to play a central role in the transcriptional regulation of many IL-6-induced genes.

Acute-Phase Proteins↗
PubMed1992

Alterations of saccadic eye movements in myotonic dystrophy.

Saccadic eye movements were examined by means of infrared reflection oculography in 8 patients having myotonic dystrophy and in 65 control subjects. In 7 patients typical alterations of the saccades could be observed. In comparison with the normal controls the saccades were significantly hypometric, of longer duration, of lower peak velocity, and showed a typical pattern of velocity and acceleration.

Adult↗
PubMed1992

Quantitative assessment of aqueous flare and aqueous 'cells' in pseudoexfoliation syndrome.

We used the laser flare-cell meter to measure aqueous flare and aqueous 'cells' in 38 eyes of 38 patients with pseudoexfoliation, in 36 normal control eyes of 36 subjects, and in 19 eyes of 19 patients with chronic open-angle glaucoma unrelated to pseudoexfoliation. In pseudoexfoliation eyes, both aqueous flare (0.61 +/- 0.55 mg/ml human albumin equivalent) and aqueous 'cells' (mean 10.70, range 0-50.6 cells/0.075 mm3) were significantly higher than in the normal control group (flare 0.15 +/- 0.06 mg/ml, 'cells' 0.43, range 0-2, P less than 0.0001) and in the glaucoma group without pseudoexfoliation (flare 0.19 +/- 0.08 mg/ml, 'cells' 0.80, range 0-2.4, P less than 0.0001 and P less than 0.005). No significant difference could be found between the flare and cell counts of normal eyes and glaucoma eyes without pseudoexfoliation (P greater than 0.09, P greater than 0.05) and between PSX eyes with (18 eyes) and without (20 eyes) open-angle glaucoma (P greater than 0.99, P greater than 0.4). Our findings indicate that the blood-aqueous barrier is impaired in eyes with pseudoexfoliation, and that the laser flare-cell meter may be a useful tool to quantify these changes. These alterations of the blood-aqueous barrier need to be considered in medical therapy and intraocular surgery.

Aged↗
PubMed1992

Tissue-specific gene expression in the pituitary: the glycoprotein hormone alpha-subunit gene is regulated by a gonadotrope-specific protein.

The molecular mechanisms for the development of multiple distinct endocrine cell types in the anterior pituitary have been an area of intensive investigation. Though the homeodomain protein Pit-1/GHF-1 is known to be involved in differentiation of the somatotrope and lactotrope lineages, which produce growth hormone and prolactin, respectively, little is known of the transcriptional regulators important for the gonadotrope cell lineage, which produces the glycoprotein hormones luteinizing hormone and follicle-stimulating hormone. Using transgenic mice and transfection into a novel gonadotrope lineage cell line, we have identified a regulatory element that confers gonadotrope-specific expression to the glycoprotein hormone alpha-subunit gene. A tissue-specific factor that binds to this element is purified and characterized as a 54-kDa protein which is present uniquely in cells of the gonadotrope lineage and is not Pit-1/GHF-1. The human and equine alpha-subunit genes are also expressed in placental cells. However, the previously characterized placental transcription factors designated TSEB and alpha-ACT are not found in the pituitary gonadotrope cells, indicating that independent mechanisms confer expression of these genes in the two different tissues.

Animals↗
PubMed1991

Intracellular responses to gonadotropin-releasing hormone in a clonal cell line of the gonadotrope lineage.

We recently derived a GnRH-responsive pituitary cell line of the gonadotrope lineage (alpha T3-1) by targeted oncogenesis in transgenic mice. Here, we report studies characterizing the GnRH receptors present in these cells and the intracellular responses to GnRH treatment. The receptors in alpha T3-1 cells show specificity for different GnRH analogs, with dissociation constants very similar to those found in normal rat and mouse pituitary. The concentration of receptors is within the range found in normal pituitary. The addition of GnRH or GnRH agonists increases phosphoinositide turnover and protein kinase-C translocation to membranes, and enhances activation of voltage-sensitive calcium channels. However, GnRH does not affect cAMP levels. Analysis of alpha-subunit mRNA levels demonstrated induction by GnRH and phorbol esters. Our results indicate that GnRH initiates a cascade of intracellular events that generate a set of second messengers, one or more of which is involved in the regulation of gene expression. The responses of alpha T3-1 cells to GnRH appear to have characteristics equivalent to those of primary pituitary gonadotropes, indicating the utility of this cell line as a model system for the study of GnRH responses.

Animals↗
PubMed1990

[Luminance contrast and color contrast evoked pattern electroretinogram in normal eyes and in eyes with glaucoma].

Pattern-onset ERGs obtained with color contrast (red-green, blue-yellow) and luminance contrast (green "black") square-wave-stripe patterns (spatial frequency 0.3 c/deg, 32 degree field) were studied in larger groups of normal and glaucomatous (chronic open-angle glaucoma) eyes. Colored stimuli were generated in a two-channel Maxwellian-view system using grating monochromators. In producing isoluminant lights of different colors, the peak latency of the response was used as a criterion. Luminance-contrast responses always have significantly smaller amplitude and shorter peak latency than color-contrast responses. This can be explained by the smaller number and shorter latency of the non-color-coded phasic anglion cells and by the larger number and longer latency of the color-coded tonic cells. Glaucomatous eyes respond with significantly smaller amplitudes at all contrast conditions tested; however, this response reduction is most pronounced with red-green patterns. Peak latencies are not significantly altered in glaucomatous eyes. Since red-green patterns are most appropriate in showing glaucoma damage in the pattern ERG, the largest absolute losses seem to occur among the large red-green antagonistic group of ganglion cells.

Aged↗
PubMed1989

A phorbol ester and phospholipid-activated, calcium-unresponsive protein kinase in mouse epidermis: characterization and separation from protein kinase C.

The phosphorylation of an Mr 82,000 protein (p82) in the Triton X-100 extract of the particulate fraction of mouse epidermis is dependent on the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) or diacylglycerol and phospholipid and, contrary to protein kinase C (PKC)-catalyzed phosphorylation, cannot be activated by calcium plus phospholipid. The novel p82 kinase differs also from PKC in many other respects, such as substrate specificity, turnover rate, and sensitivity to inhibitors. The p82 kinase can be separated from PKC by chromatography on phenyl sepharose and does not react with a polyclonal PKC antiserum. Like PKC, the novel kinase phosphorylates its substrate on threonine and serine, but not on tyrosine. Similar to PKC, the epidermal p82-kinase system is down-modulated after TPA treatment of mouse skin, with a half-life of around 5 h. Down-modulation is also accomplished by the phorbol ester RPA, but not by the Ca2+ ionophore A23187, and it is inhibited by the immunosuppressive agent cyclosporin A. In addition to down-modulation, TPA treatment of the animals activates a phosphatase that dephosphorylates phosphorylated p82 in the extract of the particulate fraction.

Animals↗
PubMed1989

The pattern-evoked electroretinogram (PERG): age-related alterations and changes in glaucoma.

Pattern-onset electroretinograms (PERGs) were studied in 147 normal subjects of different ages (14-79 years) and in 110 eyes of 65 patients with glaucoma or ocular hypertension. The responses showed an increase (P less than 0.001) in peak latency with increasing age and a decrease (P less than 0.001) in amplitude which approximately parallels the loss of ganglion cells estimated by other authors. Many glaucoma eyes showed a loss of the normally present spatial tuning. In the age group above 50 years 50% of the onset responses were significantly diminished and the peak latencies were not significantly different. A negative correlation (P less than 0.001) was found between the size of the PERG and the cup/disc ratio and a positive correlation (P less than 0.001) with the area of the neuroretinal rim of the optic disc. The PERG decreased (P less than 0.01) with increasing visual field losses.

Adolescent↗
PubMed1989

Spatial and spatiotemporal contrast sensitivity of normal and glaucoma eyes.

The spatial contrast sensitivity (CS) to static patterns was tested in the central retina of 156 normal subjects. It showed a decrease above 50 years of age at all spatial frequencies tested which was slightly more pronounced in females than in males. The spatial CS was also studied in 32 glaucoma eyes: Small reductions were found only in the group below 50 but not in eyes of patients above 50. The spatiotemporal CS to phase-reversing patterns was tested in four retinal quadrants of 99 normal subjects. It showed no age dependence in males whereas in females it decreased significantly beyond 50 years at all spatial frequencies tested. The spatiotemporal CS was studied also in 21 glaucoma eyes: Strong losses were again noted only in patients below 50. Spatiotemporal CS losses and perimetric losses were also compared in the four quadrants: For both measures the severest losses were found in the lower nasal and the mildest in the upper temporal quadrant. The spatiotemporal CS test of the peripheral retina seems to be a more powerful tool in glaucoma research than the spatial CS test of the central retina; however, effects of age and gender have to be considered.

Adult↗
PubMed1987

Isoenzyme-specific phosphorylation of cytochromes P-450 and other drug metabolizing enzymes.

A series of fourteen cytochrome P-450 isoenzymes was treated with three different protein kinases and found to divide into isoenzymes phosphorylated by both the cyclic AMP-dependent kinase and the calcium-phospholipid-dependent kinase (P-450 PB 3a and PB 2e), by none of these kinases (P-450 PB 1b, MC 1b, UT 1, and thromboxane synthase), and by either the cyclic AMP-dependent kinase (P-450 LM 2, PB 2d, and PB 3b) or the calcium-phospholipid-dependent kinase (P-450 PB 1a, PB 2a, MC 1a, LM 3c, and LM 4). Other components of the monooxygenase system, cytochrome P-450 reductase, cytochrome b5, cytochrome b5 reductase as well as microsomal epoxide hydrolase, were poor substrates for the kinases employed. On the other hand, glutathione transferases 1-2 and 4-4, but not 3-3, were relatively good substrates for the calcium-phospholipid-dependent kinase.

Animals↗
PubMed1987

Posttranslational modifications of the cytochrome P-450 monooxygenase system.

Two forms of enzymatic posttranslational modifications of the monooxygenase system are described: modification by phosphatase and modification by protein kinase. Phosphatase treatment of microsomes isolated from phenobarbital-pretreated rabbits and rats caused a marked decrease of monooxygenase activity which was paralleled by a comparable decrease of NADPH-cytochrome P-450 reductase activity while the second essential component of the system, cytochrome P-450, remained unaltered. Thus phosphatase attacks monooxygenase via reductase. Protein kinases showed the opposite preference; while cytochrome P-450 was phosphorylated, NADPH-cytochrome P-450 reductase was not. Thus the kinase affects monooxygenase via cytochrome P-450. The phosphorylation of cytochrome P-450 turned out to be a specific reaction observed only with certain cytochrome P-450 isoenzymes and certain protein kinases.

Animals↗