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Biomedical subjects

A Hofer

Publications and source records attributed to A Hofer.

At least 55 records · Page 3Linked to original sources
PubMed1999

Narrowband (311-nm) UV-B therapy for small plaque parapsoriasis and early-stage mycosis fungoides.

BACKGROUND: Broadband UV-B phototherapy has been used for many years in the treatment of small plaque parapsoriasis (SPP) and early-stage mycosis fungoides (MF). Our purpose was to investigate the effect on these diseases of narrowband (311-nm) UV-B therapy, which was recently established for the treatment of psoriasis and found to be more effective than broadband UV-B therapy. OBSERVATIONS: Twenty patients (5 women, 15 men; age range, 39-85 years) with histologically confirmed SPP or early-stage MF were enrolled. Six patients had early-stage MF (patch stage), and 14 had SPP. Treatment with 311-nm UV-B was given 3 to 4 times a week for 5 to 10 weeks. In 19 patients, lesions completely cleared after a mean number of 20 treatments (range, 14-29 treatments) and a mean cumulative UV-B dose of 16.3J/cm2 (range, 7.4-36.4 J/cm2) within a mean time of 6 weeks (range, 5-10 weeks). Biopsy specimens taken immediately after the end of phototherapy showed only sparse inflammatory infiltrates but no signs of SPP or MF. Relapses at cutaneous sites occurred in all patients within a mean time of 6 months (range, 2-15 months). CONCLUSIONS: Narrowband UV-B therapy is an effective short-term treatment modality for clearing SPP and early-stage MF. However, the treatment response did not sustain long-term remission. Further studies are necessary to examine how the clinical response to and follow-up after narrowband UV-B therapy compares with that of established phototherapy modalities in these diseases.

Adult↗
PubMed1999

A new perfusion cell chamber system for determination of heat shock effects by means of video-enhanced microscopy.

A user friendly microscope perfusion chamber which allows real-time observation of individual cells at high magnification has been designed. An integrated multisensor was used to monitor the cell culture conditions. To prove the potential of the system heat shock experiments were performed. By means of video-enhanced contrast microscopy (VECM) the mitochondria morphology of cultured astrocytes was demonstrated to change from a rod-like to an annular shape after heat shock. For further analyses mitochondria were stained on the microscope stage.

Animals↗
PubMed1999

Mitochondrial copper metabolism in yeast: mutational analysis of Sco1p involved in the biogenesis of cytochrome c oxidase.

Saccharomyces cerevisiae Sco1p is believed to be involved in the transfer of copper from the carrier Cox17p to the mitochondrial cytochrome c oxidase subunits 1 and 2. We here report on the results of a mutational analysis of Sco1p. The two cysteine residues of a potential metal-binding motif (CxxxC) are essential for protein function as shown by their substitution by alanines. Chimeras consisting of Sco1p and its homolog S. cerevisiae Sco2p restrict the specificity of Sco1p function to the N-terminal half of the protein. A candidate region for conferring specificity on Sco1p is a stretch of hydrophobic amino acids, which act as a membrane anchor. In line with this suggestion is the result that alterations of individual amino acids within this region impair Sco1p function.

Amino Acid Sequence↗
PubMed1999

Rapid impairment of skeletal muscle glucose transport/phosphorylation by free fatty acids in humans.

The initial effects of free fatty acids (FFAs) on glucose transport/phosphorylation were studied in seven healthy men in the presence of elevated (1.44 +/- 0.16 mmol/l), basal (0.35 +/- 0.06 mmol/l), and low (<0.01 mmol/l; control) plasma FFA concentrations (P < 0.05 between all groups) during euglycemic-hyperinsulinemic clamps. Concentrations of glucose-6-phosphate (G-6-P), inorganic phosphate (Pi), phosphocreatine, ADP, and pH in calf muscle were measured every 3.2 min for 180 min by using 31P nuclear magnetic resonance spectroscopy. Rates of whole-body glucose uptake increased similarly until 140 min but thereafter declined by approximately 20% in the presence of basal and high FFAs (42.8 +/- 3.6 and 41.6 +/- 3.3 vs. control: 52.7 +/- 3.3 micromol x kg(-1) x min(-1), P < 0.05). The rise of intramuscular G-6-P concentrations was already blunted at 45 min of high FFA exposure (184 +/- 17 vs. control: 238 +/- 17 micromol/l, P = 0.008). At 180 min, G-6-P was lower in the presence of both high and basal FFAs (197 +/- 21 and 213 +/- 18 vs. control: 286 +/- 19 micromol/l, P < 0.05). Intramuscular pH decreased by -0.013 +/- 0.001 (P < 0.005) during control but increased by +0.008 +/- 0.002 (P < 0.05) during high FFA exposure, while Pi rose by approximately 0.39 mmol/l (P < 0.005) within 70 min and then slowly decreased in all studies. In conclusion, the lack of an initial peak and the early decline of muscle G-6-P concentrations suggest that even at physiological concentrations, FFAs primarily inhibit glucose transport/phosphorylation, preceding the reduction of whole-body glucose disposal by up to 120 min in humans.

Adenosine Diphosphate↗
PubMed1999

Economic values for meat quality traits in pigs.

The aim for this study was to derive economic values for meat quality traits. Meat quality experts from 10 slaughter and retail companies in Switzerland were asked to give an interview in which they indicated their willingness to pay different prices for carcasses from different quality classes. Economic values for the seven meat quality traits color (L*), drip loss, intramuscular fat content, iodine value, pH1 (45 min after slaughtering), pH2 (24 to 30 h after slaughtering), and proportion of premium cuts were derived from the answers. For each trait, a weighted mean of these economic values was calculated using the number of pigs slaughtered by a company per year as a weighting factor. Population mean and standard deviation of the investigated traits were taken from station test results of Swiss Large White pigs (intramuscular fat content, iodine value, pH1, pH2, and proportion of premium cuts) and from the literature (color and drip loss). Weighted means (range among companies) of economic values per slaughter pig on the basis of one phenotypic standard deviation of the trait in Swiss Francs (SFr.) were -22.92 (0 to -62.46) for color, -10.27 (0 to -43.64) for drip loss, 10.84 (0 to 29.43) for intramuscular fat content, -29.90 (-15.54 to -43.58) for iodine value, 11.50 (.67 to 19.79) for pH1, 0 (0) for pH2, and 10.92 (-2.30 to 33.67) for proportion of premium cuts.

Animals↗
PubMed1998

Allosteric regulation of Trypanosoma brucei ribonucleotide reductase studied in vitro and in vivo.

Trypanosoma brucei is the causative agent for African sleeping sickness. We have made in vitro and in vivo studies on the allosteric regulation of the trypanosome ribonucleotide reductase, a key enzyme in the production of dNTPs needed for DNA synthesis. Results with the isolated recombinant trypanosome ribonucleotide reductase showed that dATP specifically directs pyrimidine ribonucleotide reduction instead of being a general negative effector as in other related ribonucleotide reductases, whereas dTTP and dGTP directed GDP and ADP reduction, respectively. Pool measurements of NDPs, NTPs, and dNTPs in the cultivated bloodstream form of trypanosomes exposed to deoxyribonucleosides or inhibited by hydroxyurea confirmed our in vitro allosteric regulation model of ribonucleotide reductase. Interestingly, the trypanosomes had extremely low CDP and CTP pools, whereas the dCTP pool was comparable with that of other dNTPs. The trypanosome ribonucleotide reductase seems adapted to this situation by having a high affinity for the CDP/UDP-specific effector dATP and a high catalytic efficiency, Kcat/Km, for CDP reduction. Thymidine and deoxyadenosine were readily taken up and phosphorylated to dTTP and dATP, respectively, the latter in a nonsaturating manner. This uncontrolled uptake of deoxyadenosine strongly inhibited trypanosome proliferation, a valuable observation in the search for new trypanocidal nucleoside analogues.

Allosteric Regulation↗
PubMed1998

Long-term follow-up and histological changes of superficial nonmelanoma skin cancers treated with topical delta-aminolevulinic acid photodynamic therapy.

OBJECTIVE: To investigate the immediate and long-term effects of photodynamic therapy with delta-aminolevulinic acid (ALA-PDT) on superficial basal cell carcinomas (BCC) and superficial squamous cell carcinomas (SCC). DESIGN: Retrospective study with 60 months of maximal follow-up. SETTING: University-based hospital in Graz, Austria. PATIENTS: Forty-seven subjects with a total of 95 superficial BCC and 35 superficial SCC. INTERVENTIONS: A compound of 20% delta-aminolevulinic acid was topically applied under an occlusive and light-shielding dressing before exposure to either UV-A or different wave bands of polychromatic visible light (full-spectrum visible light, >515, >570, or >610 nm). MAIN OUTCOME MEASURES: Primary tumor responses and recurrence rates in the long-term follow-up, as well as histological changes associated with ALA-PDT, were studied. RESULTS: The complete primary response rate for all wave bands of light was 86% (82/95) for superficial BCC and 54% (19/35) for superficial SCC. There was no statistically significant difference among the response rates to the different wave bands of light. After a median follow-up of 19 months (range, 3-60 months) for BCC and 8 months (range, 3-47 months) for SCC, the overall recurrence rate was 44% (36/81) and 69% (11/16), respectively. At 36 months after therapy, the projected disease-free rate was 50% (95% confidence interval, 43%-57%) for BCC vs 8% (95% confidence interval, 7%-9%) for SCC (P<.001, log-rank test). Histopathologic studies revealed a significant increase of fibrosis in the dermis after ALA-PDT and appearance of a sharp border between fibrotic and nonfibrotic tissue. In 15 of 16 BCC examined, the border between fibrotic and nonfibrotic tissue was deeper in the dermis than the maximum tumor thickness before therapy (P<.001, Wilcoxon signed rank test). Similar histopathologic observations were made in SCC. CONCLUSIONS: Our study revealed poor long-term cure rates for superficial BCC and SCC treated with topical ALA-PDT and visible light. The histopathologic observations showing remarkable fibrosis in the dermis indicated that the effect of ALA-PDT reached deeper than the initial depth of invasiveness of the neoplastic tissue, suggesting in turn that the poor long-term results of ALA-PDT cannot be explained by insufficient penetration of the therapy effect.

Administration, Topical↗
PubMed1998

Visualization and functional blocking of gap junction hemichannels (connexons) with antibodies against external loop domains in astrocytes.

Astrocytes constitute a metabolically and electrically coupled syncytium which is essential for the regulation of ionic homeostasis of the interstitial brain fluid and for coordinating responses to neuronal activities. The structural avenues that couple individual astrocytes are provided by gap junctions which consist of transmembraneous channels that bridge the extracellular space. Each gap junction channel is composed of two hemichannels (connexons) that dock to each other via their extracellular loops. Here we report on the characterization of external loop antibodies that visualize hemichannels in specific plasma membranes of vital astrocytes. Hemichannels were found to be concentrated on cytoplasmic processes and filopodia of subconfluent cells. Specificity of hemichannel-binding was evaluated by blockage of Lucifer Yellow (LY) dye-transfer and Ca2+ transmission, as well as LY uptake under calcium-deficient conditions. Our data indicate that hemichannels are accessible from the extracytoplasmic side either for direct visualization or functional manipulation. The availability of such a probe will allow in vivo experiments which require selective and/or temporal blocking of gap junctions in animal models.

Animals↗
PubMed1998

In situ observation of living pericytes in rat retinal capillaries.

We observed the retinal capillary pericytes of the rat in situ. Whole retinae were mounted, immediately post vivo, in a special tissue chamber for electronic light microscopy at high magnifications. Under electronic light microscopy the pericytes could be clearly distinguished from the endothelial cells. In addition, the contractile apparatus of the pericytes was demonstrated by immunohistochemistry with alpha-smooth muscle actin. Administration of angiotensin II as well as endothelin into the observation chamber caused a significant decrease of the mean capillary diameter (13 and 16% reduction, respectively) within 90 s. Carbachol, bradykinin, and histamine significantly increased the capillary diameter within 90 s (13, 20, and 18% increase, respectively). This study demonstrates that our method allows the analysis of vasoactive effects on the retinal capillary in situ. We observed that this type of capillary can actively change its diameter.

Actins↗
PubMed1998

Immunohistochemical distribution of connexin 43 in the cartilage of rats and mice.

Using fluorescence immunohistochemistry, the distribution of connexin 43 was examined in hyaline cartilage and in the perichondrium of mouse and rat knee joints. In addition, rat chondrocytes were shown to be coupled in dye transfer studies with Lucifer Yellow. Connexin 43 was detected between chondrocytes in the outer layer of knee joint cartilage, between chondrocytes of the growth plate and between fibrocartilage-like cells at tendon and ligament insertions and in the tendons and ligaments proper. However, in the hyaline cartilage of the hind limbs of mature rats, the degree of connexin 43 immunoreactivity was diminished. These data suggest a possible involvement of connexins in cartilage development.

Aging↗
PubMed1998

Hints of a functional connection between the neuropeptidergic innervation of arteriovenous anastomoses and the appearance of epithelioid cells in the rabbit ear.

Peripheral blood flow can be regulated by specialized vessel segments, the arteriovenous anastomoses. Their wall consists of a relatively thick layer of smooth muscle cells and so-called epithelioid cells. The epithelioid cell is a specialized myogenic cell phenotype expressing nitric oxide synthase. We studied the innervation of the different segments of arteriovenous anastomoses in the rabbit ear using antisera against neuropeptide Y, tyrosine hydroxylase, calcitonin gene-related peptide and substance P, as well as neuron-specific enolase, calbindin D and neurotubulin. The participation was especially examined of neuropeptidergic innervation and a possible morphological connection to the occurrence of epithelioid cells and a paracrine function. The NADPH diaphorase reaction and alpha-smooth muscle actin immunoelectron microscopy served to distinguish epithelioid cells from smooth muscle cells. Using conventional fluorescence microscopy and confocal laser scanning microscopy, we found the most dense innervation pattern of pan-neuronal markers (neurotubulin, neuron-specific enolase), tyrosine hydroxylase-immunoreactive nerve fibres and neuropeptidergic nerve fibres (neuropeptide Y, calcitonin gene-related peptide, substance P) around the intermediate segment in arteriovenous anastomoses, whereas the venous segment was barely marked. Single nerve fibres penetrated into the medial layer and reached the epithelioid cells. Using immunoelectron microscopy, we found intercellular contacts between epithelioid cells, but not the gap junction protein connexin 43. Here, we report for the first time a correlation of the innervation pattern with epithelioid cell type in arteriovenous anastomoses. Our findings suggest that epithelioid cells of the arteriovenous anastomoses are controlled by a dense network of neuropeptidergic nerve fibres in functional connection to their paracrine role as a nitric oxide producer.

Animals↗
PubMed1998

Comparison of phototherapy with near vs. far erythemogenic doses of narrow-band ultraviolet B in patients with psoriasis.

The therapeutic effectiveness of radiation from a 311 nm ultraviolet B (UVB) lamp (Philips TL-01) in a near vs. far erythemogenic therapy regimen was investigated in 13 patients with widespread, symmetrically distributed psoriasis. The patients received UV therapy starting with 70% of the 311 nm minimal erythema dose (MED) on one randomly chosen half of the body and 35% of the 311 nm MED on the other half. Therapy was given three to five times a week, and the UVB dose in both regimens was increased simultaneously in the same relation. For the 11 patients completing the study, the mean psoriasis area and severity index (PASI) score for the near vs. far erythemogenic treatment side was 21.2 vs. 18.5 before therapy (Wilcoxon's test, not significant), 11.8 vs. 14.4 at week 1 (P = 0.003), 8.2 vs. 12.0 at week 2 (P = 0.004), and 6.6 vs. 15.6 at week 3 (P = 0.005). After 3 weeks, a satisfactory response (i.e. improvement of the initial PASI score by more than 75%) was observed in six of 11 patients on the near erythemogenic treatment side vs. three of 11 patients on the far erythemogenic side. However, the definitive median total number of treatments needed to achieve a satisfactory therapy response on the near vs. far erythemogenic sides was 12 vs. 16 (P = 0.022), whereas the definitive median cumulative UV dose was 14.0 vs. 9.1 J/cm2 (P = 0.088), respectively. These results suggest that near erythemogenic 311 nm UVB therapy may clear psoriasis faster than far erythemogenic therapy but that the latter regimen may be equally effective as it requires slightly more treatment sessions at a lower (and possibly less carcinogenic) cumulative UV dose.

Adult↗
PubMed1998

Electronic light microscopy combined with spectrophotometry allows real-time analysis of structures at the subcellular level.

A combination of microscopy (video-enhanced contrast microscopy) and spectrophotometry (which analyses online the spectra from the microscopic picture) is presented. This set-up allows the in vivo microscopic observation of cellular and subcellular structures as well as simultaneous online determination of cellular chromophores. To test our equipment we measured spectra of isolated red blood cells and NG 108-15 cells and correlated these spectra with the corresponding video-enhanced microscopic picture. By labelling specific cell organelles of astrocytes with in vivo fluorescent dyes, we visualized mitochondria and captured the corresponding spectra.

Animals↗