Topical tacrolimus for oral cicatricial pemphigoid.
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Administration, Topical↗
Biomedical subjects
J Becker
Publications and source records attributed to J Becker.
Cytologic and DNA-cytometric very early diagnosis of oral cancer.
BACKGROUND: The aim of this study was to evaluate the diagnostic accuracy of exfoliative cytology (EC) and DNA-image cytometry applied to suspicious oral lesions compared with synchronous histology. METHODS: Brush- and scalpel biopsies were obtained from 98 patients with suspicious oral lesions. In cases, in which EC revealed malignant or suspicious cells, nuclear DNA-contents were measured using a TV image analysis system. RESULTS: Among 98 oral lesions both cytological and histological diagnosis showed no sign of malignancy or dysplasia in 75. In 23 cases cytology yielded tumor cell-positive (15), suspicious (four) or doubtful (four) results. DNA-cytometry showed aneuploidy in 19 of these. The comparison between cytological diagnosis combined with DNA-cytometry and biopsy-histology resulted in a sensitivity of 100% and a specificity of 97.4%. CONCLUSION: In conclusion, cytology with DNA-cytometry is a highly sensitive, specific and non-invasive method for the early diagnosis of oral epithelial neoplasia, showing excellent compliance among patients.
Adult↗
The lymphatic vascular system: secondary or primary?
It has generally been accepted that the blood vascular system is primary and the lymphatic vascular system secondary. Diseases of the blood vascular system are the leading cause for mortality and morbidity in developed nations. In contrast, lymphedema is seldom life-threatening and can generally be well-managed by combined physiotherapy. During ontogeny, the blood vessels and the heart develop much earlier than the lymphatic vessels. However, there is growing evidence that the first vascular system occurring during ontogeny and phylogeny has lymphatic functions. Defense mechanisms are crucial for all organisms irrespective of their size. Macrophages precede the emergence of erythrocytes during ontogeny, and their circulation in the hemolymphatic (more accurately, lymphohematic) system of insects, which do not possess erythrocytes, shows that the lymphatic function is primary whereas the nutritive function is secondary, needed only in larger organisms. In molluscs and arthropods, which have an open vascular system, hemocyanin has both oxygen transporting and defense functions. In vertebrates, the early blood vessels have structural characteristics of lymphatics and express the lymphendothelial receptor flt-4 (Vascular Endothelial Growth Factor Receptor-3). Later, flt-4 becomes restricted to the definitive lymphatics, which are either formed from the primary vessels or from mesodermal lymphangioblasts. The primary lymphatic function has become overruled by the nutritive function in blood vessels of larger animals. The circular movement of cells is driven by a blood heart, which, however, is not an unique organ. Lymph hearts are present in lower vertebrates, still develop transiently in birds, and are vestigial in the contractile lymphangion which "circulates" immune cells. We conclude that the definitive lymphatics are perhaps secondary in mammals, but the blood vascular system seems to develop on the basis of an ancestral lymphatic system with lymph hearts.
Animals↗
Response to systemic HIV viral load suppression correlates with psychomotor speed performance.
The authors evaluated the association of a virologic response to highly active antiretroviral therapy, or a subsequent rebound, with performance on two measures of psychomotor speed in HIV-positive subjects. Virologic suppression was associated with improved performance on measures of psychomotor speed, and virologic rebound was associated with psychomotor speed performance decline. Changes in plasma HIV viral load in HIV-positive individuals with cognitive slowing correlate with performance on tests of psychomotor speed.
AIDS Dementia Complex↗
Determination of phosphorus in small amounts of protein samples by ICP-MS.
Inductively coupled plasma mass spectrometry (ICP-MS) is used for phosphorus determination in protein samples. A small amount of solid protein sample (down to 1 micro g) or digest (1-10 micro L) protein solution was denatured in nitric acid and hydrogen peroxide by closed-microvessel microwave digestion. Phosphorus determination was performed with an optimized analytical method using a double-focusing sector field inductively coupled plasma mass spectrometer (ICP-SFMS) and quadrupole-based ICP-MS (ICP-QMS). For quality control of phosphorus determination a certified reference material (CRM), single cell proteins (BCR 273) with a high phosphorus content of 26.8+/-0.4 mg g(-1), was analyzed. For studies on phosphorus determination in proteins while reducing the sample amount as low as possible the homogeneity of CRM BCR 273 was investigated. Relative standard deviation and measurement accuracy in ICP-QMS was within 2%, 3.5%, 11% and 12% when using CRM BCR 273 sample weights of 40 mg, 5 mg, 1 mg and 0.3 mg, respectively. The lowest possible sample weight for an accurate phosphorus analysis in protein samples by ICP-MS is discussed. The analytical method developed was applied for the analysis of homogeneous protein samples in very low amounts [1-100 micro g of solid protein sample, e.g. beta-casein or down to 1 micro L of protein or digest in solution (e.g., tau protein)]. A further reduction of the diluted protein solution volume was achieved by the application of flow injection in ICP-SFMS, which is discussed with reference to real protein digests after protein separation using 2D gel electrophoresis.The detection limits for phosphorus in biological samples were determined by ICP-SFMS down to the ng g(-1) level. The present work discusses the figure of merit for the determination of phosphorus in a small amount of protein sample with ICP-SFMS in comparison to ICP-QMS.
Animals↗
A system for studying genetic changes in Candida albicans during infection.
Candida albicans is a diploid yeast with a dimorphic life history. It exists commensally in many healthy humans but becomes a potent pathogen in immunocompromised hosts. The underlying genetic mechanisms by which C. albicans switches from a commensal to a pathogenic form in the host are not well understood. To study the evolution of virulence in mammalian hosts, we used GAL1 as selectable marker system that allows for both positive and negative selection in selective media. We show that the deletion of one or both copies of GAL1 in the C. albicans genome does not change virulence in a systemic mouse model. We obtained estimates for the frequency of mitotic recombination at the GAL1 locus during systemic infection. Our observations suggest that genetic changes such as mitotic recombination and gene conversion occur at a high enough frequency to be important in the transition of C. albicans from a commensal to a pathogenic organism.
Animals↗
Visually detectable resolution of intraoral dental films.
OBJECTIVES: The visually utilizable resolution of intraoral dental films was examined with the naked eye, with two-fold optical magnification and after digitization using a computer display. METHODS: Agfa Dentus M2, Kodak Ektaspeed Plus and Kodak InSight dental films were exposed with a line pair (lp) test pattern providing frequencies up to 16.6 lp mm(-1). Films were developed at 24 degrees C in a Dürr Periomat machine and at 28 degrees C in a Dürr AC245 machine. Forty dental students evaluated the maximum visually detectable resolution with their naked eye, with an X-ray viewer (providing two-fold magnifying lenses and eliminating disturbing light) and following digitization and monitor display examination. RESULTS: The best detectable resolution was achieved through digitization, reaching a mean of up to 16.5 lp mm(-1). With two-fold magnification, a mean of up to 13.3 lp mm(-1) could be resolved, while only 11.7 lp mm(-1)could be resolved with the naked eye. Unlike the other film types, the resolution of Ektaspeed depended on the processing type when viewing digitized images or when viewing with the naked eye. There was a trend for students above 29 years of age to detect a lower resolution with the naked eye, although they performed comparably with students below 29 years when using the X-ray viewer or viewing digitized images. CONCLUSIONS: Film resolution is utilized best through digitization and secondly using a magnifying lens. With the naked eye, a mean of 11 lp mm(-1) with a broad distribution can be resolved. A magnifying lens is recommended if resolution is important or if the viewer's eyesight is reduced. Compared with E-speed films, Kodak Insight was less dependent on processing conditions.
Adult↗
A comparison of conventional panoramic radiographs with volumetric computed tomography images in the preoperative assessment of impacted mandibular third molars.
PURPOSE: In the present study, we evaluated the geometric, topographic, and anatomic reliability of volumetric computed tomography (VCT) images by comparing conventional panoramic radiographs with reconstructed VCT panoramic and paraxial images before performing third molar surgery. PATIENTS AND METHODS: A total of 6 anatomic sites on 10 patients who showed a topographic relationship between the apices of the third molar root and the mandibular canal were preoperatively assessed by 5 oral surgeons using conventional panoramic radiographs; these were complemented and compared with secondary reconstructed paraxial and panoramic VCT images. RESULTS: The position of the apices in relation to the mandibular canal could be revealed on 94% of VCT reconstructed paraxial images. Assessment of VCT paraxial images could be facilitated by using a toolbar marker in 70% of the paraxial images. In 90% of the paraxial images, it was possible to assess the relationship of the mandibular canal and its adjacent anatomy. The visual grading scores for conventional panoramic images were significantly better on all 7 assessed anatomic sites compared with the reconstructed VCT panoramic images. CONCLUSION: The results showed that the VCT paraxial images gave a significantly clearer perception of the mandibular nerve than conventional panoramic radiographs. However, conventional panoramic radiographs were shown to be better than the VCT reconstructed panoramic images and were therefore an invaluable tool in the "expert-derived" assessment and posed the potential for identifying the need for further VCT diagnostic procedures.
Adult↗
[Effects of a high intensity training program on patients with chronic obstructive airways disease (COAD)].
UNLABELLED: In a controlled/prospective clinical trial we examined 125 patients with moderate COAD, 84 of which performed a high-intensity training program on cycle ergometers. METHODS: All participants (controls n = 39, training-group n = 84, age 48.7 versus 48.1 years, FEV1 62.3 % vs. 63.1 % of predicted) were examined spiroergometrically (ramp protocol, increment 10 W/min), the anaerobic threshold (AT) determined and a training intensity calculated (AT + 40 % of the difference to peak exercise). Training was carried out on cycle ergometers with 5 training units weekly at 40 minutes each. We aimed at a minimum of 22 training units during 4 weeks. RESULTS: Both groups improved in the lung function at rest (FEV1 + 11 % versus + 12 % in the controls). Only for the training group we found a statistically significant improvement in maximum exercise capacity (O2 uptake + 286.4 ml vs. + 72.4 ml, maximum workrate + 20.0 watts vs. + 5.7 W), of the anaerobic threshold (AT improved by 8.4 watts vs. 5.1 W) as well as in the metabolic load (lactate decreased by 1.3 mmol vs. 0.2 mmol, ventilation decreased by 3.8 l/min vs. 2.3 l/min). In most subscales of the SF-36 questionnaire quality of living improved more clearly in the training group, whereas the LAQ questionnaire showed no group-specific differences and no improvement after training. CONCLUSION: We conclude from the result that a high intensity training program can be recommended as a useful and low-risk component in pulmonary rehabilitation programs.
Educational Measurement↗
Association of microbial community composition and activity with lead, chromium, and hydrocarbon contamination.
Microbial community composition and activity were characterized in soil contaminated with lead (Pb), chromium (Cr), and hydrocarbons. Contaminant levels were very heterogeneous and ranged from 50 to 16,700 mg of total petroleum hydrocarbons (TPH) kg of soil(-1), 3 to 3,300 mg of total Cr kg of soil(-1), and 1 to 17,100 mg of Pb kg of soil(-1). Microbial community compositions were estimated from the patterns of phospholipid fatty acids (PLFA); these were considerably different among the 14 soil samples. Statistical analyses suggested that the variation in PLFA was more correlated with soil hydrocarbons than with the levels of Cr and Pb. The metal sensitivity of the microbial community was determined by extracting bacteria from soil and measuring [(3)H]leucine incorporation as a function of metal concentration. Six soil samples collected in the spring of 1999 had IC(50) values (the heavy metal concentrations giving 50% reduction of microbial activity) of approximately 2.5 mM for CrO(4)2- and 0.01 mM for Pb2+. Much higher levels of Pb were required to inhibit [14C]glucose mineralization directly in soils. In microcosm experiments with these samples, microbial biomass and the ratio of microbial biomass to soil organic C were not correlated with the concentrations of hydrocarbons and heavy metals. However, microbial C respiration in samples with a higher level of hydrocarbons differed from the other soils no matter whether complex organic C (alfalfa) was added or not. The ratios of microbial C respiration to microbial biomass differed significantly among the soil samples (P < 0.05) and were relatively high in soils contaminated with hydrocarbons or heavy metals. Our results suggest that the soil microbial community was predominantly affected by hydrocarbons.
Bacteria↗
The wireless monitoring of vital parameters: a design study.
This project shows the way vital parameters can be transmitted and visualized with no connecting cables necessary to the PDA. This was realized using a sensor developed with an integrated Bluetooth interface and a PDA, also equipped with Bluetooth. This radio connection can span up to 10 m, and parameters, such as pulse frequency, oxygen saturation in blood, ECG measurements and plethysmograms, can be transmitted. Using the software introduced in this work, the transmitted measurements can be displayed numerically or graphically on the PDA. The software simultaneously checks for any limits and sends a warning message if these limits are exceeded. All received data are additionally documented.
Computer Graphics↗
CSF antiretroviral drug penetrance and the treatment of HIV-associated psychomotor slowing.
The authors evaluated whether highly active antiretroviral therapy (HAART) with multiple CSF-penetrating drugs results in greater improvement in HIV-associated psychomotor slowing than HAART with a single CSF-penetrating drug. Both groups had improvement in CD4 count, plasma viral load, as well as two tests of psychomotor speed. Comparing the two groups, there were no differences in the mean change for CD4 count, viral load, or any of the neuropsychological tests. Multiple and single CSF-penetrating HAART may be equivalent for treating HIV-associated psychomotor slowing.
Adult↗
Stimulation of nuclear export and inhibition of nuclear import by a Ran mutant deficient in binding to Ran-binding protein 1.
Receptor-mediated nucleocytoplasmic transport is dependent on the GTPase Ran and Ran-binding protein 1 (RanBP1). The acidic C terminus of Ran is required for high affinity interaction between Ran and RanBP1. We found that a novel Ran mutant with four of its five acidic C-terminal amino acids modified to alanine (RanC4A) has an approximately 20-fold reduced affinity for RanBP1. We investigated the effects of RanC4A on nuclear import and export in permeabilized HeLa cells. Although RanC4A promotes accumulation of the nuclear export receptor CRM1 at the cytoplasmic nucleoporin Nup214, it strongly stimulates nuclear export of GFP-NFAT. Since RanC4A exhibits an elevated affinity for CRM1 and other nuclear transport receptors, this suggests that formation of the export complex containing CRM1, Ran-GTP, and substrate is a rate-limiting step in export, not release from Nup214. Conversely, importin alpha/beta-dependent nuclear import of bovine serum albumin, coupled to a classical nuclear localization sequence is strongly inhibited by RanC4A. Inhibition can be reversed by additional importin alpha, which promotes the formation of an importin alpha/beta complex. These results provide physiological evidence that release of Ran-GTP from importin beta by RanBP1 and importin alpha is critical for the recycling of importin beta to a transport-competent state.
Binding Sites↗
[Cell therapy with dendritic cells].
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Antigen-Antibody Complex↗
Treatment of cicatricial pemphigoid with mycophenolate mofetil as a steroid-sparing agent.
BACKGROUND: Cicatricial pemphigoid (CP) is a rare autoimmune bullous disease that affects the skin and mucous membranes. It commonly ends by serious complications such as blindness, stenosis, and stricture formation and is difficult to treat. Mycophenolate mofetil has been reported to be effective in the treatment of pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid either as monotherapy or as a steroid-sparing agent. OBJECTIVE: Our purpose was to evaluate the effectiveness of mycophenolate mofetil as a steroid-sparing agent in treating patients with CP. METHODS: Three patients with CP were treated with mycophenolate mofetil and prednisolone. RESULTS: All 3 patients responded very well to the therapy. None of them showed relapse of the disease for a follow-up period of 6 to 14 months after complete cessation of mycophenolate mofetil and prednisolone. No side effects were seen. CONCLUSION: Mycophenolate mofetil appears to be a safe and effective steroid-sparing agent in the treatment of CP.
Anti-Inflammatory Agents, Non-Steroidal↗
Treatment of neonatal thrombus formation with recombinant tissue plasminogen activator: six years experience and review of the literature.
BACKGROUND: Thrombosis is a relatively rare event in children. However, many conditions in the neonatal period result in an increased risk of thrombus formation. The major risk factor is the indwelling intravascular catheter. Numerous small studies have reported experience of thrombolytic treatment for neonatal thrombotic disease with a wide range of different thrombolytic agents in various forms of administration, dosage, and duration, but no conclusions on the most effective treatment for neonates has been reached. OBJECTIVE: To assess the efficacy and safety of thrombolytic treatment of neonatal catheter related thrombus (CRT) formation with recombinant tissue plasminogen activator (rt-PA). METHOD: Over a six year period, 14 neonates with CRT were treated with the same rt-PA protocol (an initial bolus of 0.7 mg/kg over 30-60 minutes followed by infusion of 0.2 mg/kg/h). RESULTS: Complete clot dissolution was documented in 11 patients, and partial clot lysis in two patients, leading to a patency rate of 94%. In two cases, local bleeding occurred, resulting in treatment failure in one case. Finally, antithrombin III substitution was required in one case. No other complications such as severe bleeding were recognised. CONCLUSION: With the use of close clinical and haematological monitoring on a neonatal intensive care unit combined with serial two dimensional colour echocardiography, the present rt-PA protocol was shown to be a safe and effective method of clot dissolution in neonates.
Anticoagulants↗
Structural and biochemical properties show ARL3-GDP as a distinct GTP binding protein.
BACKGROUND: Based on sequence similarities, Arf-like (ARL) proteins have been assigned to the Arf subfamily of the superfamily of Ras-related GTP binding proteins. They have been identified in several isoforms in a wide variety of species. Their cellular function is unclear, but they are proposed to regulate intracellular transport. RESULTS: The 1.7 A crystal structure of murine ARL3-GDP provides a first insight into the structural features of this subgroup of Ar proteins. The N-terminal extension of ARL3 folds into an elongated loop region that is hydrophobically anchored onto the surface by burying 1440 A2. The features observed suggest that ARL3 releases its N terminus and undergoes a beta sheet register shift upon the binding of GTP. The structure and kinetic experiments with fluorescent mGDP demonstrate that tight GDP (but not GTP) binding is achieved in the absence of a magnesium ion. This is due to a lysine residue in the active site, close to the canonical Mg2+ site found in other GTP binding proteins. This is a distinct feature separating ARL2 and ARL3 from Arf proteins. CONCLUSION: The disturbed magnesium binding site and the independence of GDP coordination from the presence of Mg2+ separate ARL2 and ARL3 from Arf proteins. The D sheet register shift, which is similar to that of Arf, that is observed in the present structure, along with the postulated release of the N-terminal extension and the concomitant exposure of a patch of conserved hydrophobic residues in this region suggest that ARL proteins might be localized to target membranes upon exchange of GDP to GTP. Contrary to the situation in Arf, however, the conformational change to ARL-GTP does not require the presence of membranes and might thus be energetically unfavored. Together with the very low affinity described for the interaction of ARL3 with Mg-GTP, this suggests that ARL protein activation requires the presence of effectors stabilizing the GTP coordination rather than guanine nucleotide exchange factors (GEFs).
ADP-Ribosylation Factor 1↗