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Biomedical subjects

D Wagner

Publications and source records attributed to D Wagner.

At least 109 records · Page 6Linked to original sources

Chromophore-bearing NH2-terminal domains of phytochromes A and B determine their photosensory specificity and differential light lability.

In early seedling development, far-red-light-induced deetiolation is mediated primarily by phytochrome A (phyA), whereas red-light-induced deetiolation is mediated primarily by phytochrome B (phyB). To map the molecular determinants responsible for this photosensory specificity, we tested the activities of two reciprocal phyA/phyB chimeras in diagnostic light regimes using overexpression in transgenic Arabidopsis. Although previous data have shown that the NH2-terminal halves of phyA and phyB each separately lack normal activity, fusion of the NH2-terminal half of phyA to the COOH-terminal half of phyB (phyAB) and the reciprocal fusion (phyBA) resulted in biologically active phytochromes. The behavior of these two chimeras in red and far-red light indicates: (i) that the NH2-terminal halves of phyA and phyB determine their respective photosensory specificities; (ii) that the COOH-terminal halves of the two photoreceptors are necessary for regulatory activity but are reciprocally inter-changeable and thus carry functionally equivalent determinants; and (iii) that the NH2-terminal halves of phyA and phyB carry determinants that direct the differential light lability of the two molecules. The present findings suggest that the contrasting photosensory information gathered by phyA and phyB through their NH2-terminal halves may be transduced to downstream signaling components through a common biochemical mechanism involving the regulatory activity of the COOH-terminal domains of the photoreceptors.

Amino Acid Sequence↗

Control of rod retinomotor movements in teleost retinae: the role of dopamine in mediating light-dependent and circadian signals.

In the retinae of lower vertebrates, several morphological changes, including photomechanical movements of rods, cones and pigment epithelium, occur during light and dark adaptation. We studied the contribution of exogenous and endogenous circadian control mechanisms to rod retinomotor movements in the teleost retina and their dependence on an intact dopaminergic system. Blue acara (Aequidens pulcher) were kept under a 12:12 h light/dark cycle. One population of fish remained untreated; another population was treated with 6-hydroxy-dopamine, selectively to destroy dopaminergic cells. Rod positions were determined in semi-thin radial sections. During the normal light/dark cycle, rods were elongated during the day and contracted at night. Rod retinomotor movements persisted during two cycles of continuous darkness. Expected light levels of rod positions were reduced by about 40% in comparison with normal light phases. Adaptation-dependent retinomotor movements and movements driven by an endogenous circadian clock also occurred in dopamine-depleted retinae. No statistically significant differences were observed between dopamine-containing and dopamine-depleted retinae. We conclude that rod retinomotor movements in teleost retinae are controlled by light and by an endogenous circadian clock. Dopamine plays no essential role in the light-dependent and endogenous control of rod retinomotor movements.

Animals↗

Mutational analysis of phytochrome B identifies a small COOH-terminal-domain region critical for regulatory activity.

Overexpression of phytochrome B (phyB) in transgenic Arabidopsis results in enhanced deetiolation in red light. To define domains of phyB functionally important for its regulatory activity, we performed chemical mutagenesis of a phyB-overexpressing line and screened for phenotypic revertants in red light. Four phyB-transgene-linked revertants that retain parental levels of full-length, dimeric, and spectrally normal overexpressed phyB were identified among 101 red-light-specific revertants. All carry single amino acid substitutions in the transgene-encoded phyB that reduce activity by 40- to 1000-fold compared to the nonmutagenized parent. The data indicate that the mutant molecules are fully active in photosignal perception but defective in the regulatory activity responsible for signal transfer to downstream components. All four mutations fall within a 62-residue region in the COOH-terminal domain of phyB, with two independent mutations occurring in a single amino acid, Gly-767. Accumulating evidence indicates that the identified region is a critical determinant in the regulatory function of both phyB and phyA.

Amino Acid Sequence↗

Phytochromes: photosensory perception and signal transduction.

The phytochrome family of photoreceptors monitors the light environment and dictates patterns of gene expression that enable the plant to optimize growth and development in accordance with prevailing conditions. The enduring challenge is to define the biochemical mechanism of phytochrome action and to dissect the signaling circuitry by which the photoreceptor molecules relay sensory information to the genes they regulate. Evidence indicates that individual phytochromes have specialized photosensory functions. The amino-terminal domain of the molecule determines this photosensory specificity, whereas a short segment in the carboxyl-terminal domain is critical for signal transfer to downstream components. Heterotrimeric GTP-binding proteins, calcium-calmodulin, cyclic guanosine 5'-phosphate, and the COP-DET-FUS class of master regulators are implicated as signaling intermediates in phototransduction.

Photoreceptor Cells↗

Efficacy trial of topically administered interferon gamma-1 beta gel in comparison to laser treatment in cervical intraepithelial neoplasia.

OBJECTIVE: Dose dependent response of cervical intraepithelial neoplasia (CIN) to topically administered interferon (IFN) gamma was assessed and compared with conventional laser therapy. PATIENT AND METHODS: 33 women were included in a randomized phase II trial which was double blinded for IFN dosages. Twenty-four patients received IFN gamma-1 beta gel and a control group of nine patients was treated with laser surgery. 18 patients had smears suggesting CIN II and 15 patients had smears suggesting CIN III. The response was assessed 6 months after starting of IFN gamma-1 beta treatment or having laser surgery. RESULTS: Topical IFN gamma-1 beta treatment gave a cure rate of 42% independent of IFN dosage as compared to an 89% cure rate with laser therapy (P = 0.02). Patients with CIN II responded better compared with patients with CIN III. Current smokers showed a significantly lower cure rate whereas use of oral contraceptives (OC) did not influence response. High viral load with high risk types of human papillomaviruses (HPV) was associated with a better response.

Administration, Intravaginal↗

Threshold of tactile sensitivity perceived with dental endosseous implants and natural teeth.

The aim of this study was to determine the threshold of tactile perception of endosseous dental implants and to assess the relative difference of that threshold between implants and teeth. Twenty-two subjects with implants of the ITI Dental Implant System were included in the study. All implants served as abutments for single tooth crowns and had been in function for a minimum of 1 year. A strain gauge glued to the shaft of an amalgam plugger served as a force sensor. It transformed the elastic deformation exerted onto the shaft into an electronic signal for recording. By use of the amalgam plugger, a continuously increasing force was exercised on the implants or teeth until the first sensation of touch was indicated by the patient. Statistical analysis revealed threshold values for the implants ranging from 13.2 to 189.4 g (1 g = 0.01 N) (mean 100.6; SD 47.7), while a range of 1.2 to 26.2 g (mean 11.5; SD 11.5) was found for control teeth. Thus, the mean threshold values for implants were 8.75 times higher than for teeth. This difference was highly statistically significant. A general linear models procedure was applied to determine the influence of patient age, jaw, implant position and the threshold values of teeth on the measurements obtained for implants. Only gender and the threshold values for contralateral teeth had a significant influence. These 2 parameters together explained 27% of the variability in threshold measurements. It is concluded that a more than 8-fold higher threshold value for tactile perception exists for implants compared with teeth.

Adolescent↗

Flowering responses to altered expression of phytochrome in mutants and transgenic lines of Arabidopsis thaliana (L.) Heynh.

The long-day plant Arabidopsis thaliana (L.) Heynh. flowers early in response to brief end-of-day (EOD) exposures to far-red light (FR) following a fluorescent short day of 8 h. FR promotion of flowering was nullified by subsequent brief red light (R) EOD exposure, indicating phytochrome involvement. The EOD response to R or FR is a robust measure of phytochrome action. Along with their wild-type (WT) parents, mutants deficient in either phytochrome A or B responded similarly to the EOD treatments. Thus, neither phytochrome A nor B exclusively regulated flowering, although phytochrome B controlled hypocotyl elongation. Perhaps a third phytochrome species is important for the EOD responses of the mutants and/or their flowering is regulated by the amount of the FR-absorbing form of phytochrome, irrespective of the phytochrome species. Overexpression of phytochrome A or phytochrome B resulted in differing photoperiod and EOD responses among the genotypes. The day-neutral overexpressor of phytochrome A had an EOD response similar to all of the mutants and WTs, whereas R EOD exposure promoted flowering in the overexpressor of phytochrome B and FR EOD exposure inhibited this promotion. The comparisons between relative flowering times and leaf numbers at flowering of the over-expressors and their WTs were not consistent across photoperiods and light treatments, although both phytochromes A and B contributed to regulating flowering of the transgenic plants.

Arabidopsis↗

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Germany↗

Medical student knowledge levels and performance in doing HIV risk assessment.

The primary purpose of the study was to develop and evaluate a training program for medical students in sexual history-taking and HIV risk assessment. Sexual-history-taking performance was evaluated in the semester subsequent to the one in which the students received the instruction. An additional purpose of the study was to determine whether students, following participation in a sexual-history training program, would take a sexual history when course instructions did not explicitly direct her/him to do so but the patient presented with HIV risk factors. A final goal was to find out whether direct participation in, versus only observation of, sexual-history interviews would improve performance. Adequate performance on measurement on knowledge and skills was defined as above 75% correct on content examinations and satisfactory performance of the sexual history. Results showed that, when course instruction directed students to take a sexual history, performance was excellent. When students were not specifically directed to take a sexual history, but the patient had an HIV risk factor, performance was not as consistent. Following participation in the training program, student attitudes about the importance of taking a sexual history were very positive. Finally, when a student conducted a sexual-history interview him/herself, compared with viewing other students taking a history, he/she showed no significant improvement in examination performance.

Clinical Competence↗

Quantitative X-ray microanalysis of P, Ca, and S in the mucus secretory granules of the cryofixed frog palate epithelium.

In respiratory epithelium, the mucus is densely packed inside the secretory granules (SG) of secretory cells (SC) before being released by exocytosis in the airway lumen. We have previously shown that the frog palate is a representative model of respiratory epithelium and that rapid cryofixation is a very effective technique in preserving the integrity of the mucus SG. The concentration of phosphorus (P), sulphur (S), and calcium (Ca) were analysed inside the SG of the SC of frog palate after quick freezing, cryosubstitution, and embedding in Lowicryl resin at low temperature. The experiments were carried out using X-ray microanalysis conducted with energy dispersive spectrometry (EDS) at 100 kV. The quantitation was carried out using the continuum method with reference to Agar standards. The cryofixation permitted us to distinguish two types of SG depending on whether they were electron dense (serous cells) or electron-lucent (mucous cells). A significant (P < 0.001) difference in the S concentration was observed between the individual serous (239 +/- 79 mmol.kg-1) and the mucous SG (161 +/- 48 mmol.kg-1). No significant difference could be identified in the Ca concentration between the two SG phenotypes. In the serous SG, the P content was high (41 +/- 17 mmol.kg-1) compared with the mucous SG where it was not measurable. The comparison of the three element concentrations in each type of secretory cells showed that significant differences in concentration of S and Ca concentration could be observed from one SC cell to another.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Liposomal doxorubicin in AIDS-related Kaposi's sarcoma: long-term experiences.

Treatment of AIDS-related Kaposi's sarcoma with cytotoxic chemotherapy is limited by toxicities of the various agents. Liposomal doxorubicin is a new treatment option for patients with Kaposi's sarcoma with potentially reduced toxicity. Three AIDS patients with different stages of tumor risk were enrolled in a study evaluating the safety and efficacy of liposomal doxorubicin at a dose of 10-20 mg/m2 every 2-4 weeks. Maximal duration of treatment was 86 weeks with a cumulative dose of 560 mg/m2. Criteria proposed by the AIDS Clinical Trials Group were used to define tumor stages and response to therapy. All patients showed partial responses after 40-100 mg/m2 total dose with reduction of tumor-associated edema and flattening of more than 50% of previously nodular or plaque-like lesions. One patient showed progressive disease after discontinuation of treatment for 8 weeks; Kaposi's sarcoma responded again partially on retreatment. Progression was also seen in one patient after dose reduction due to granulocytopenia and again during treatment of active cytomegalovirus retinitis. Serial measurements of cutaneous target lesion surface area did not indicate response. Increases in surface area, however, correlated with progressive disease. Toxicities included moderate leukopenia, aphthous stomatitis, and transient alopecia. Liposomal doxorubicin may well be valuable for long-term treatment of AIDS-associated Kaposi's sarcoma, especially in patients with extensive disease. However, controlled comparison with conventional treatment regimens is mandatory.

Acquired Immunodeficiency Syndrome↗

Hepatitis B vaccination of immunosuppressed heart transplant recipients with the vaccine Hepa Gene 3 containing pre-S1, pre-S2, and S gene products.

The antibody response of immunosuppressed heart transplant recipients to vaccination with the hepatitis B (HB) virus vaccine Hepa Gene 3 (HG-3), containing HB virus pre-S1, pre-S2, and S gene products, was examined. Three heart transplant recipients who had been vaccinated preoperatively against HB responded well to the vaccination. Five of 38 patients (13.2%) vaccinated postoperatively before HG-3 vaccination with the second-generation vaccine Gen-H-B-Vax-D (37 without and 1 with detectable anti-HBs response) and 3 of 24 (12.5%) without previous HB vaccination developed protective anti-HBs titers (greater than 10 U/l) after immunization with the HG-3 vaccine. The low response rate (8/62, 12.9%) found for postoperatively vaccinated patients indicates that heart transplant recipients should be vaccinated against HB before immunosuppressive medication.

Adult↗

Nosocomial hepatitis B virus infections in cardiac transplant recipients transmitted during transvenous endomyocardial biopsy.

Between March 1986 and September 1990, 67 of 243 cardiac transplant recipients in outpatient care at our clinic became hepatitis B virus surface antigen (HBsAg) positive after operation. The HBsAg of 63 patients belonged to the subtype ay, suggesting a common source of infection. These 63 cases and 103 controls with negative hepatitis B virus (HBV) serology were studied in order to analyse the outbreak. The sources of infection were patients who were chronic HBsAg carriers. Infection was transmitted at the time of endomyocardial biopsy, if performed on the same day and in the same room after biopsy of an HBsAg positive patient. The most likely mode of HBV transmission was droplet contamination of instruments and/or medication vials used for subsequent patients. Performing biopsies on HBsAg positive and negative patients in separate rooms resulted in the termination of the outbreak.

Adult↗

Pattern of endothelin immunostaining during rejection episodes after kidney transplantation.

A pathophysiological role for endothelin (ET), one of the most potent vasoconstrictor peptides, has been suggested in ATN and during kidney allograft rejection. As ET is known to have predominantly local effects, we investigated intrarenal ET content in 82 kidney transplant biopsies and 10 normal control kidneys. ET-immunostaining, using a polyclonal anti-ET-1 antibody was investigated in 4 intrarenal vascular beds (glomeruli, capillaries, arterioles, arteries) and in tubular epithelium. Normal kidneys showed a strong staining of endothelial cells in all vessels and of tubular epithelium. In biopsies with signs for acute vascular rejection a marked decrease in ET staining intensity was seen. In contrast, normal staining similar to control kidneys was detected in interstitial rejection and in ATN. The presence of chronic CyA toxicity, however, lead to a significant reduction of endothelial ET staining. Neither mean doses nor trough levels of CyA correlated closely with the immunostaining findings. Plasma big-ET levels were elevated during vascular rejection, but not in interstitial rejection and ATN. This study demonstrates a significant reduction of ET immunostaining in intrarenal vascular endothelium of kidney transplant biopsies showing signs of endothelial damage. In vascular allograft rejection these changes are often associated with a concomitant rise in plasma ET levels. Our findings support a postulated role of ET in vascular rejection and during CyA toxicity and show that endothelial damage, independent of its genesis, can lead to a reduction of intrarenal ET content.

Adult↗