Showing papers by "University of Bern published in 1993"

Somatostatin receptor scintigraphy with [111In-DTPA-d-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients

Abstract: Various tumours, classically specified as either neuroendocrine or non-neuroendocrine, contain high numbers of somatostatin receptors, which enable in vivo localization of the primary tumour and its metastases by scintigraphy with the radiolabelled somatostatin analogue octreotide. In addition granulomas and autoimmune processes can be visualized because of local accumulation of somatostatin receptor-positive activated mononuclear leucocytes. In many instances a positive scintigram predicts a favourable response to treatment with octreotide. It is tempting to speculate that octreotide labelled with an appropriate radionuclide might be used in cancer therapy. The successful application of radiolabelled octreotide in scintigraphy indicates the possible usefulness of other radiolabelled peptides, either native peptides or derivatives of these, in, for example, nuclear oncology. The small size of these peptides, e.g. bombesin and substance P, is of the utmost importance for a relatively fast blood clearance, thus leading to low background radioactivity. In this way peptides are powerful alternatives to (fragments of) monoclonal antibodies, the application of which to scintigraphic localization of specific cell surface antigen-bearing tumours is plagued by slow blood clearance and, hence, high background levels.

Rapid identification of mycobacteria to the species level by polymerase chain reaction and restriction enzyme analysis.

Abstract: A method for the rapid identification of mycobacteria to the species level was developed on the basis of evaluation by the polymerase chain reaction (PCR) of the gene encoding for the 65-kDa protein. The method involves restriction enzyme analysis of PCR products obtained with primers common to all mycobacteria. Using two restriction enzymes, BstEII and HaeIII, medically relevant and other frequent laboratory isolates were differentiated to the species or subspecies level by PCR-restriction enzyme pattern analysis. PCR-restriction enzyme pattern analysis was performed on isolates (n = 330) from solid and fluid culture media, including BACTEC, or from frozen and lyophilized stocks. The procedure does not involve hybridization steps or the use of radioactivity and can be completed within 1 working day.

Atmospheric carbon dioxide and the ocean

Abstract: The ocean is a significant sink for anthropogenic carbon dioxide, taking up about a third of the emissions arising from fossil-fuel use and tropical deforestation. Increases in the atmospheric carbon dioxide concentration account for most of the remaining emissions, but there still appears to be a 'missing sink' which may be located in the terrestrial biosphere.

Recommendations for standards in transthoracic two-dimensional echocardiography in the dog and cat

Abstract: Recommendations are presented for standardized imaging planes and display conventions for two-dimensional echocardiography in the dog and cat. Three transducer locations ("windows") provide access to consistent imaging planes: the right parasternal location, the left caudal (apical) parasternal location, and the left cranial parasternal location. Recommendations for image display orientations are very similar to those for comparable human cardiac images, with the heart base or cranial aspect of the heart displayed to the examiner's right on the video display. From the right parasternal location, standard views include a long-axis four-chamber view and a long-axis left ventricular outflow view, and short-axis views at the levels of the left ventricular apex, papillary muscles, chordae tendineae, mitral valve, aortic valve, and pulmonary arteries. From the left caudal (apical) location, standard views include long-axis two-chamber and four-chamber views. From the left cranial parasternal location, standard views include a long-axis view of the left ventricular outflow tract and ascending aorta (with variations to image the right atrium and tricuspid valve, and the pulmonary valve and pulmonary artery), and a short-axis view of the aortic root encircled by the right heart. These images are presented by means of idealized line drawings. Adoption of these standards should facilitate consistent performance, recording, teaching, and communicating results of studies obtained by two-dimensional echocardiography.

The protein tyrosine kinase JAK1 complements defects in interferon-α/β and -γ signal transduction

Abstract: We have produced a cell line which lacks the protein tyrosine kinase JAK1 and is completely defective in interferon response. Complementation of this mutant with JAK1 restored the response, establishing the requirement for JAK1 in both the interferon-α/β and -γ signal transduction pathways. The reciprocal interdependence between JAK1 and Tyk2 activities in the interferon-α pathway, and between JAK1 and JAK2 in the interferon-γ pathway, may reflect a requirement for these kinases in the correct assembly of interferon receptor complexes.

Localized ridge augmentation using guided bone regeneration. 1. Surgical procedure in the maxilla.

Abstract: The principle of guided bone regeneration can be applied for localized ridge augmentation in a staged approach. The surgical procedure for the mandible is presented through three case reports. Incision technique and flap design, utilization of autogenous bone grafts as a membrane-supporting device and osteoconductive scaffold, proper placement of barrier membranes and their stabilization with miniscrews, and wound closure are all emphasized. Furthermore, factors essential for achieving predictable results with barrier membranes for localized ridge augmentation and the benefits of combining barrier membranes with autogenous bone grafts are discussed.

Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins

Abstract: Binding of interferons IFN-alpha and IFN-gamma to their cell surface receptors promptly induces tyrosine phosphorylation of latent cytoplasmic transcriptional activators (or Stat proteins, for signal transducers and activators of transcription). Interferon-alpha activates both Stat91 (M(r) 91,000; ref. 1) and Stat113 (M(r) 113,000; ref. 2) whereas IFN-gamma activates only Stat91 (refs 3, 4). The activated proteins then move into the nucleus and directly activate genes induced by IFN-alpha and IFN-gamma. Somatic cell genetics experiments have demonstrated a requirement for tyrosine kinase-2 (Tyk2) in the IFN-alpha response pathway and for Jak2 (ref. 6), a kinase with similar sequence, in the IFN-gamma response pathway. Here we investigate the tyrosine phosphorylation events on Stat and Jak proteins after treatment of cells with IFNs alpha and gamma and with epidermal growth factor (EGF). Stat91 is phosphorylated on Tyr701 after cells are treated with IFN-alpha and EGF, as it was after treatment with IFN-gamma (ref. 8). We find that Jak1 also becomes phosphorylated on tyrosine after cells are treated with these same three ligands, although each ligand is shown to activate at least one other different kinase. Jak1 may therefore be the enzyme that phosphorylates Tyr 701 in Stat91.

Bisphosphonates act on rat bone resorption through the mediation of osteoblasts.

Abstract: Bisphosphonates are generally considered to act on bone resorption by binding to bone mineral and subsequently inhibiting the activity of the osteoclasts which ingest them. This has been supported by the fact that bisphosphonates adsorbed on mineralized tissue inhibit the resorbing activity of isolated osteoclasts in vitro. However, the effectiveness of different bisphosphonates determined in this system does not reflect their relative potencies in vivo. Employing the well-described isolated osteoclast resorption pit assay, with ivory as the resorption substrate, we show here that this lack of correlation prevails only when the bisphosphonates are added to the mineral before addition of osteoclasts, but not when the cells are treated for a short time (5 min) before allowing them to adhere onto ivory. By using this approach with five different bisphosphonates, a stringent correlation of relative potencies was obtained with those found, both in the rat and in the human, in vivo. Furthermore, by using an osteoblastic cell line (CRP 10/30) which is a powerful promoter of osteoclastic resorption in vitro, we obtained evidence that the inhibitory effect of bisphosphonates was the result of an action on osteoblasts rather than on osteoclasts. Thus, in experiments in which the osteoblastic cells were pretreated for 5 min with bisphosphonates and then cocultured with osteoclasts, inhibition of osteoclastic resorbing activity was obtained. Moreover, it was found that this treatment resulted in a decrease of the stimulatory effect found in CRP 10/30-conditioned medium. In conclusion the present study shows that part of the osteoclast inhibiting action of the bisphosphonates is mediated through an action on osteoblasts.

The reproducibility of classification of fractures of the proximal end of the humerus.

Abstract: The radiographs of ninety-five fractures of the proximal end of the humerus were classified with the Neer and the AO/ASIF systems by five orthopaedic surgeons who had a special interest in problems of the shoulder. Without access to their initial interpretations, the same five orthopaedic surgeons reevaluated the same radiographs eight weeks later. Intraobserver and intraobserver reliability were found to be fair or poor for both classification systems. Kappa values for the interobserver reliability were 0.40 for the Neer system and 0.53 for the AO/ASIF system. When the fractures were subclassified, according to the recommendations of the AO/ASIF, into groups and subgroups, reproducibility became progressively worse. Intraobserver reliability showed kappa values of 0.60 and 0.58, respectively. A so-called extended radiographic trauma series, consisting of three perpendicular radiographs, was available for thirty-five fractures; the third perpendicular projection did not significantly improve the reproducibility values for either classification compared with those obtained with only two perpendicular projections. We concluded that neither the Neer nor the AO/ASIF classification of fractures of the proximal end of the humerus is sufficiently reproducible to allow meaningful comparison of similarly classified fractures in different studies.

The role of interleukin-8 in inflammation and mechanisms of regulation.

Abstract: Interleukin-8 (IL-8) is a chemoattractant cytokine produced by a variety of tissue and blood cells. Unlike many other cytokines, it has a distinct target specificity for the neutrophil, with only weak effects on other blood cells. Interleukin-8 attracts and activates neutrophils in inflammatory regions. The importance of neutrophil functions has been recognized in periodontal disease for many years. Neutrophils represent the major population of immigrant cells in periodontitis. In diseases with neutrophil dysfunctions periodontal tissue is lost very rapidly. The response of neutrophils to IL-8 is characterized by migration of the cells, the release of granule enzymes, and other intra- and extracellular changes. Connective tissue constituents are efficiently degraded by neutrophil enzymes, released upon activation. Interleukin-8 is a member of the Interleukin-8 supergene family that includes other small chemotactic peptides with structural homology. It also shares with other cytokines DNA sequence features that suggest common regulatory pathways. In vivo intracutaneous application of IL-8 induces local exudation and a massive, long-lasting accumulation of neutrophils. Though IL-8 plays a role in the cytokine network, its major pathophysiological role lies in affecting neutrophils. This article presents a review of literature on the current knowledge of IL-8, its mechanisms of expression, and the effects it exerts on the neutrophil.

Retinal separation, retinotomy, and macular relocation: II. A surgical approach for age-related macular degeneration?

Abstract: Three cases of age-related maculopathy with severe and recent massive submacular hemorrhage were treated by performing complete vitrectomy. A total retinal detachment was created by infusion of fluid underneath the retina, followed by a peripheral circumferential retinotomy. This allowed access to the subretinal space for removal of blood and membranes and, more importantly, permitted rotation of the retina with relocation of the fovea. Rotations between 30° and 80° were achieved. One patient with 5 months' follow-up had a visual improvement from 1/200 to 20/80 and excyclorotation of images. The other two patients developed proliferative vitreoretinopathy after initially successful rotation. Their retinas were reattached after surgical removal of the membranes and silicone oil tamponade, but visual function remained low. The rationale for this treatment is that relocating the fovea to an area where pigment epithelium is less diseased than in the central area may allow for recovery of some useful vision.

Periodontal regeneration of human intrabony defects. IV. Determinants of healing response.

Abstract: The purpose of this study was to identify factors which might affect the healing response in intrabony defects treated with guided tissue regeneration. Selected sites presented with deep periodontal lesions with 1, 2, and 3 wall combination intrabony component of 6.1 +/- 2.5 mm. The significance of patient, tooth, and defect characteristics and surgical parameters as predictor variables affecting the regenerative outcome before and following the removal of the barrier membrane was assessed. Outcome was measured as tissue gain under the membrane, regenerated probing attachment level (PAL), and bone fill. The total depth of the intrabony component and the radiographic defect angle significantly affected the amount of tissue gain. Seventy-five percent (75%) of the variability of regenerated PAL and bone fill was explained in terms of tissue gain under the membrane, radiographic width of the defect angle, full mouth bleeding score, and presence or absence of flap coverage of the newly formed tissue. Control of the identified predictor variables might improve the extent and predictability of guided tissue regeneration in the treatment of deep intrabony defects.

Poor plasma status of carotene and vitamin C is associated with higher mortality from ischemic heart disease and stroke: Basel Prospective Study.

Abstract: Previous cross-cultural comparisons of the mortality from ischemic heart disease in European communities with associated plasma levels of essential antioxidants have revealed strong inverse correlations for vitamin E and relatively weak correlations for other antioxidants Similarly, in a case-control study in Edinburgh low plasma levels of vitamin E were significantly associated with an increased risk of previously undiagnosed angina pectoris whereas low levels of other essential antioxidants lacked statistical significance The current Basel Prospective Study is particularly well suited to elucidate the impact of antioxidants other than vitamin E In this population (which was recently evaluated regarding cancer mortality) the plasma levels of vitamins E and A are exceptionally high and above the presumed threshold level of risk for ischemic heart disease The present 12-year follow-up of cardiovascular mortality in this study reveals a significantly increased relative risk of ischemic heart disease and stroke at initially low plasma levels of carotene (< 023 mumol/l) and/or vitamin C (< 227 mumol/l), independently of vitamin E and of the classical cardiovascular risk factors Low levels of both carotene and vitamin C increase the risk further, in the case of stroke even with significance for overmultiplicative interaction In conclusion, in cardiovascular disease independent inverse correlations may exist for every major essential antioxidant although the latter can also interact synergistically Therefore future intervention trials of antioxidants in the prevention of ischemic heart disease should primarily test the simultaneous optimization of the status of all principal essential antioxidants

Detection of interstellar pick-up hydrogen in the solar system.

Abstract: Interstellar hydrogen ionized primarily by the solar wind has been detected by the Solar Wind Ion Composition Spectrometer instrument on the Ulysses spacecraft at a distance of 4.8 AUs from the sun. This 'pick-up' hydrogen is identified by its distinct velocity distribution function, which drops abruptly at twice the local solar wind speed. From the measured fluxes of pick-up protons and singly charged helium, the number densities of neutral hydrogen and helium in the distant regions of the solar system are estimated to be 0.077 +/- 0.015 and 0.013 +/- 0.003 per cu cm, respectively.

Tumour necrosis factor-α induces superoxide anion generation in mitochondria of L929 cells

Abstract: Within a few minutes after addition to L929 cells, tumour necrosis factor-alpha (TNF alpha) induced an increase in lucigenin-enhanced chemiluminescence that could be inhibited by superoxide dismutase. The generation of superoxide anion (O2.-) was sensitive to treatment with rotenone, antimycin A and cyanide, indicating that the signal originated from mitochondria. The mechanism of production of O2.- was shown to be independent of ATP synthesis, as uncoupling of this event from mitochondrial electron transport did not alter the generation of O2.- induced by TNF alpha. Chemiluminescence was further dependent on the presence of extracellular calcium, suggesting a role for this cation as a second messenger. This hypothesis was supported by the finding that inhibition of mitochondrial calcium uptake by Ruthenium Red exerted a protective effect on TNF alpha-treated L929 cells. Increased O2.- generation was followed by a marked decrease in mitochondrial dehydrogenase activity and cellular ATP levels, while cell membrane permeability was moderately increased. A role for mitochondrial O2.- generation in TNF alpha cytotoxicity was further supported by the finding that resistant L929 cells had decreased ability to produce O2.- in response to TNF alpha. In addition, we detected a decreased activity of the mitochondrial enzyme succinate dehydrogenase in these cells, suggesting that this component of the respiratory chain might be an important contributor to the TNF alpha-induced generation of O2.-.

Periodontal Regeneration of Human Infrabony Defects. I. Clinical Measures

Abstract: A series of investigations was undertaken to evaluate the extent and predictability of periodontal regeneration with barrier membranes in deep infrabony defects. This study reports the clinical outcomes in terms of probing attachment level (PAL) gains, probing pocket depth (PPD) reduction, and recession (REC) of marginal gingiva. Forty deep 1, 2, and 3-wall combination infrabony defects treated with membranes were evaluated 1 year postoperatively following a strict plaque control regimen (mean plaque score = 6.1%, bleeding score = 4% at 1 year). A PAL gain of 6.1 +/- 2.5 mm along with a PPD reduction of 5.9 +/- 2.5 mm were observed. A PAL gain of 2 mm or more was detected in almost 90% of the treated sites. No site lost attachment. Residual PPD was 3 mm or shallower in 95% of the sites. It is concluded that treatment of deep infrabony defects according to the principles of guided tissue regeneration and a strict plaque control regimen represents an efficacious and predictable treatment alternative.

Prospects for the prevention of free radical disease, regarding cancer and cardiovascular disease

Abstract: Free radicals may be involved in the aetiology of cancer and cardiovascular diseases. In epidemiological studies poor plasma levels of all essential antioxidants are associated with increased relative risks; in particular, low levels of carotene and vitamin E with the risk of cancer and ischemic heart disease, respectively. The studies suggest that for optimal synergistic protection the plasma antioxidant levels should simultaneously exceed the threshold values of 28-30 mumol/l lipid-standardized vitamin E, 40-50 mumol/l vitamin C, 0.4-0.5 mumol/l carotene and 2.2-2.8 mumol/l lipid-standardized vitamin A. However the preventive efficacy of an optional antioxidant status is still to be proven in randomized intervention trials. Although these antioxidant micronutrients may be the primary protective components of vegetable-rich 'preventive' diets, the potentials of other plant components await exploration, eg carotenoids other than beta-carotene, bioflavonoids and oxygen-sensitive B-vitamins.

Direct, automated detection of rifampin-resistant Mycobacterium tuberculosis by polymerase chain reaction and single-strand conformation polymorphism analysis

Abstract: A rapid screening test was recently established for the detection of mutations in the rpoB gene of Mycobacterium tuberculosis, a region identified as the locus for rifampin resistance (Rifr). The detection method involved the amplification by polymerase chain reaction (PCR) of the Rifr region and the identification of mutations by single-strand DNA conformation polymorphism analysis (SSCP) of the amplification products. Experience using two different PCR-SSCP formats for the evaluation of BACTEC cultures and sputum is presented here; the previously described manual procedure for the detection for the detection of radiolabelled amplification products and an automated SSCP by which fluorescein-labelled products were detected on a Pharmacia DNA sequencer apparatus. All 17 different Rifr mutations known to date were consistently detected. PCR-SSCP could be used for the evaluation of minimally grown cultures (BACTEC 12B medium with a growth index of < or = 100) and for direct screening of microscopically positive sputa with greater than 10 organisms per field (magnification, x250). Implementation of this technique could result in rapid detection of rifampin resistance in M. tuberculosis, a marker of multidrug-resistant tuberculosis.

Positive genetic correlation between female preference and preferred male ornament in sticklebacks

Abstract: A NUMBER of population genetics models predict the evolution of male sexual ornaments through female choice1, but their genetic assumptions and predictions have hardly been investigated2,3. A key feature of these models is a positive genetic correlation between male ornaments and female preference for them4. Here I test this prediction at the within-population level with three-spined sticklebacks, Gasterosteus aculeatus, which show conspicuous sexual dichromatisnr. Intense red males are preferred in various situations6–10, but there is great intrapopulational variation in redness both among wild-caught6,10 and among laboratory-bred males11, which is partly environmental6 and may be partly genetic12,13. Also, females show considerable intrapopulational variation in their preference for redder males6,8,9, which is partly environmental8,9. Wild-caught, intense red males and dull males were crossed with a number of females from the same population in a full-sib/half-sib breeding design. Daughters were tested for their preference for more intensely red males, and the sons' coloration was quantified. Both traits showed genetic variation. Also the redness of the sons correlated with the preference for red of their sisters, thus the two traits show positive genetic correlation.

Radiological analysis of normal axial alignment of femur and tibia in view of total knee arthroplasty

Abstract: Alignment of the anatomical and mechanical axes of the lower extremities was analyzed using standardized radiographs in two series of 66 femur and 44 tibia specimens. A new anatomical axis, the distal femoral anatomical axis, was introduced. This axis corresponds to the overall femoral anatomical axis and encloses a valgus angle of 6o with the mechanical axis of the femur. It allows for design of shorter intramedullary guiding instruments that will still be in congruency with true femur geometry. Comparison with computerized calculations of angles on computed tomography scans on a series of 38 bones shows a high precision of measurement on standard radiographs in neutral rotation.

The Influence of Different Factors on in vitro Enamel Erosion

Abstract: The aim of this study was to use two demineralization test methods to analyze the erosive potential of beverages and foodstuffs. In addition, the surface microhardness test and the iodide permeability test were compared. Surface microhardness and iodide permeability were measured before and after exposure. To characterize the beverages and foodstuffs the content of phosphate, calcium and fluoride, pH, the titrable amount of base to pH 5.5 and 7.0 as well as the buffer capacity at pH 5.5 were determined. Sprite light showed the highest significant decrease in surface microhardness (p≤0.05) followed by grapefruit juice, apple juice and salad dressing. The highest significant increase in iodide permeability (p≤0.05) was caused by exposure to grapefruit juice followed by apple juice (Sprite light was not tested). Multiple linear regression analyses revealed that the erosive capacity of different drinks, juices and foodstuffs are statistically significantly associated with their acidity, pH values, phosphate and fluoride contents as well as the baseline surface microhardness or iodide permeability values of the exposed enamel.