Search PubMed⌕ Search

Biomedical subjects

F Wolf

Publications and source records attributed to F Wolf.

At least 37 records · Page 2Linked to original sources

The Rotational Spectrum of OCCCS Revisited.

The rotational spectrum of the linear chain molecule tricarbon oxide sulfide, OCCCS, was recorded at room temperature between 118 and 179 GHz using a new commercial millimeter-wave spectrometer. The observed transitions were analyzed together with hitherto unassigned transitions from measurements between 78 and 118 GHz. About 1900 rotational transitions of OCCCS in the vibrational ground state and in 13 excited bending states could be assigned, the latter including the eighth, ninth, and tenth excited state of the low-lying bending mode nu(7) as well as the second excited state of the bending mode nu(6). Besides the determination of effective constants for these newly identified vibrational states, our data also served to considerably improve the effective constants for some of the bending states already characterized in previous publications. Copyright 2000 Academic Press.

Journal Article↗

Genomic amplification of the human plakophilin 1 gene and detection of a new mutation in ectodermal dysplasia/skin fragility syndrome.

Ectodermal dysplasia/skin fragility syndrome is a recently described autosomal recessive disease affecting skin, nails, and hair (MIM 604536), that results from mutations in plakophilin 1, a structural component of desmosomes. We report a new plakophilin 1 mutation in an affected patient as well as detailing the intron-exon organization of the gene to facilitate future polymerase chain reaction-based mutation screening. Using polymerase chain reaction amplification of genomic DNA, we identified 15 exons spanning approximately 50 kb. Direct sequencing disclosed several nonpathogenic intragenic polymorphisms, as well as a homozygous splice site mutation (1233-2 A-->T; GenBank Z73678) in a 17 y old affected male. The clinical features comprised skin erosions, dystrophic nails, sparse hair, and painful thickening and cracking of palms and soles. Skin biopsy showed negative immunolabeling with an anti-plakophilin 1 antibody and small desmosomes. These results expand the database of plakophilin 1 mutations and demonstrate the importance of this protein in the stabilization of desmosomal adhesion in terminally differentiating keratinocytes.

Adolescent↗

Platelets and cytokines in concert with endothelial activation in patients with peripheral arterial occlusive disease.

We tested the hypothesis whether circulating oncostatin-M (OSM), a cytokine that in vitro promotes fibrinogen biosynthesis and smooth muscle cell proliferation, or soluble CD40 ligand (CD40L; CD154), a leukocyte and platelet surface marker that stimulates endothelial cells, were associated: (a) with fibrinogen and other soluble cell adhesion molecules, such as P-selectin, vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 and platelet-endothelial cell adhesion molecule-1; or (b) with restenosis and platelet activation in 71 patients with peripheral arterial occlusive disease undergoing peripheral angioplasty (PTA). Platelet membrane activation markers (CD62P, CD63, activated GPIIb/IIIa) were immunologically measured at 0, 1, 24 and 48 h, and 3 and 6 months after PTA. Soluble cell adhesion molecules, endothelial markers and various hemostatic variables were measured before PTA. Of the patients, 42.3% developed restenosis within 6 months, defined as a >50% reduction of the lumen at the site of balloon dilatation. Soluble CD40L was not higher in the restenosis group. Interestingly, patients with high CD40L showed significantly higher soluble VCAM-1 (P < 0.01) and thrombomodulin (P < 0.01), as well as trends for higher soluble P- and E-selectin. Platelet activation was found uniformly increased mostly at 1 and 24 h, as well as at 3 and 6 months. OSM was measurable in 53.5% (6.9 +/- 9.4 pg/ml) of the patients and undetectable in the others. No differences in the rate of restenosis was found in these two groups, which did not differ with respect to fibrinogen (3.14 +/- 1.00 versus 3.21 +/- 0.70 g/l), or the other parameters. In conclusion, soluble CD40L is associated with higher endothelial biological markers that might implicate its involvement in endothelial activation. Platelet activation, probably intermittent, might play a significant role through the expression of CD40L as a source of activation signals to the endothelial cells. Free circulating OSM does not seem to correlate directly with fibrinogen or with other acute phase reaction proteins, the synthesis of which it could influence in vitro. This might well not mean, however, that OSM lacks this activity in vivo.

Aged↗

Guess what! SALT - related B-cell lymphoma presenting as a xanthomatous infiltration of the neck.

A 37-year-old man without previous medical history working as a lock keeper was seen in our unit for a progressive painless subcutaneous flesh coloured infiltration of the lower anterior area of the neck growing slowly over 5 months. Clinical cutaneous findings showed a non pruriginous yellowish papulonodular eruption mimicking xanthomas (Figs. 1 and 2). No other clinical abnormalities were found. A cutaneous biopsy specimen was performed. Histopathological examination revealed, under a normal epidermis, a dense lymphoplasmocytoid infiltrate involving the dermis with periadnexal and perivascular reinforcement (Figs. 3 and 4).

Adult↗

[Chicken pox recurrence revealing a renal adenocarcinoma in an adult].

A new episode of chicken pox in adults who had a well documented infection previously is usually observed in immunocompromised individuals. The principal immunodeficiency factors are hematology diseases, acquired immunodeficiency disease and old age. We report here the case of a young woman who after a contaminating contact presented a recurrence of typical chicken pox. Morphological investigations evidenced a right kidney tumor which pathology revealed to be a renal adenocarcinoma. We discuss this pathological association and review cases reported in the literature.

Acyclovir↗

Circulating cell adhesion molecules and endothelial markers before and after transluminal angioplasty in peripheral arterial occlusive disease.

In the present study, the levels of soluble adhesion molecules P- and E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and of other markers of endothelial activation or injury, such as thrombomodulin, von Willebrand factor (vWF), as well as homocysteine, were prospectively investigated in 71 patients (21 women, 50 men, age 68+/-13) with predominantly femoropopliteal peripheral arterial occlusive disease (PAOD, stage II-IV, Fontaine) before and after percutaneous transluminal angioplasty (PTA). Thirty patients (42.3%) developed restenosis within 6 months, defined as a > 50% reduction of the lumen diameter at the site of PTA. At entry in the study, 46% and 58% of all patients had higher than normal levels of soluble P-selectin and VCAM-1, respectively. Thrombomodulin (P < 0.01) measured at entry, was significantly higher in patients who developed late restenosis, with trends for higher values for P-selectin, VCAM-1 and vWF. The relative risks for developing restenosis were 2.41 (CI95%: 1.23-4.75) and 1.54 (CI95%: 0.98-2.72) for thrombomodulin and P-selectin, respectively. Soluble P-selectin and the severity of PAOD (Fontaine stage III/IV) were found to be statistically indicative factors for late restenosis in a logistic regression risk factor analysis with an overall predictive value of 72%. At 6 months, those who developed restenosis had also higher soluble P-selectin (P < 0.01), VCAM-1 (P < 0.05) and a trend for higher thrombomodulin. Homocysteine was elevated in 52% of the patients at entry but neither was it associated with higher restenosis rates nor did it correlate with the levels of thrombomodulin or the other adhesion molecules. These findings indicate that patients with PAOD have to a significant proportion, elevated levels of circulating soluble adhesion molecules and markers of endothelial activation occurring in concert with an ongoing atherosclerotic process.

Aged↗

Expression of the vitamin D receptor, of estrogen and thyroid hormone receptor alpha- and beta-isoforms, and of the androgen receptor in cultures of native mouse bone marrow and of stromal/osteoblastic cells.

Marrow stromal cells mediate the effect of 1alpha,25-dihydroxyvitamin D3 on formation of osteoclast-like cells from undifferentiated hematopoetic precursors in bone marrow. Induction by the vitamin D hormone of multinucleated, calcitonin receptor- and tartrate-resistant acid phosphatase-positive cells in primary mouse bone marrow culture can be modulated by other members of the steroid/thyroid hormone family, such as triiodothyronine, which has a positive effect, as well as 17beta-estradiol and 5alpha-dihydrotestosterone, which both act as inhibitors of osteoclastogenesis. In an attempt to relate these effects of the steroid/thyroid hormones to the presence of their respective nuclear receptors, we studied expression of the vitamin D receptor (VDR), estrogen receptor (ER)-alpha and -beta, thyroid hormone receptor (TR)-alpha and -beta, and androgen receptor (AR) in total bone marrow as well as primary marrow stromal cell cultures. By using reverse-transcriptase-polymerase chain reaction, in both cases amplification products were obtained, which were identified by multiple restriction fragment length analysis as transcripts from mRNA specific for the ligand-binding domains of the VDR, ER-alpha, ER-beta, TR-alpha, TR-beta, and AR. Specific immunostaining by indirect peroxidase labeling revealed that among the various cell types present in bone marrow, the steroid/ thyroid hormone receptors are abundant particularly in marrow stromal cells. In another series of experiments, we extended our survey on receptor expression also to stromal/osteoblastic cell lines. At the mRNA level, the complete repertoire of steroid/thyroid hormone receptors was present in preadipocytic ST2 cells as well as in osteoblastic MC3T3-E1 cells. By immunocytochemical staining of the latter, it became apparent that single cells exhibit wide variations in intensity of specific signals for all the receptors investigated, so that, notably in contrast to primary stromal cells and ST2 cells, MC3T3-E1 display a mosaic pattern of receptor protein expression.

3T3 Cells↗

In vivo stability and metabolism of 99Tcm-labelled anti-CD4 monoclonal antibodies and Fab' fragments.

In a comparative study, the in vivo metabolic profile of 99Tcm-anti-CD4 monoclonal antibodies (MAb) and Fab' fragments (direct thiol-reduction method) was investigated in rats with adjuvant arthritis. Plasma samples were obtained 1, 4 and 15 h following intravenous injection and urine was collected over 15 h. The composition of the radiolabelled molecules was analysed by gel filtration chromatography. The profile of the complete MAb was as follows. (1) Serum: a predominant peak of 150 kDa (complete MAb; approximately 80%); three minor peaks of 125, 100 and 50 kDa (presumably H2L1, H2 and H1 chains; 14%); and two small peaks of approximately 1500 and 300 Da (presumably 99Tcm-glutathione and Cys-99Tcm-Cys; 5%). (2) Urine: minor peaks of 125, 100 and 50 kDa (15%), major peaks of 1500 and 300 Da (50%), and an additional 25-kDa peak (30%). The profile of the Fab' was as follows. (1) Serum: three minor peaks of 150 kDa [conceivably F(ab')2 plus soluble-CD4], 110 kDa [F(ab')2] and 95 kDa (Fab' plus soluble-CD4; together 30%); a predominant peak of 55 kDa (Fab'; 61%); and two minor peaks of 1500 and 300 Da (8%). (2) Urine: predominantly a 55 kDa (16%) and 1500 and 300 Da peaks (74%). Also, the anti-CD4 Fab' showed higher urine excretion and lower plasma levels than the complete anti-CD4 MAb, but still more favourable tissue-to-blood ratios following scintigraphy of the arthritic joints. Thus, the complex metabolic profile of the anti-CD4 Fab' does not appear to interfere with specific targeting of the inflamed synovial membrane.

Animals↗

Theory of ocular dominance pattern formation.

We investigate a general and analytically tractable model for the activity-dependent formation of neuronal connectivity patterns. Previous models are contained as limiting cases. As an important example we analyze the formation of ocular dominance patterns in the visual cortex. A linear stability analysis reveals that the model undergoes a Turing-type instability as a function of interaction range and receptive field size. The phase transitions is of second order. After the linear instability the patterns may reorganize which we analyze in terms of a potential for the dynamics. Our analysis demonstrates that the experimentally observed dependency of ocular dominance patterns on interocular correlations of visual experience during development can emerge according to two generic scenarios: either the system is driven through the phase transition during development thereby selecting and stabilizing the first unstable mode or a primary pattern reorganizes towards larger wavelength according their lower energy. Experimentally observing the time course of ocular dominance pattern formation will decide which scenario is realized in the brain.

Algorithms↗

Linear cutaneous lupus erythematosus in an adult.

We report on a 32-year-old female with a 3-year history of an asymptomatic erythema of the forehead. The lesion had a linear distribution following the lines of Blaschko. Histopathological findings and direct immunofluorescence allowed to establish the diagnosis of cutaneous lupus erythematosus. Treatment with local corticosteroid and antimalarial agents given for 2 months resulted in a complete remission.

Adolescent↗

Effect of gentian violet, corticosteroid and tar preparations in Staphylococcus-aureus-colonized atopic eczema.

BACKGROUND: In atopic eczema (AE), skin colonization with Staphylococcus aureus plays a possible role in the pathophysiology of the disease. METHODS: Thirty-eight patients with AE were screened for their cutaneous colonization with S. aureus. The antibacterial and clinical efficacy of topical therapy with the antiseptic dye gentian violet, a potent glucocorticosteroid or a tar solution (liquor carbonis detergens) was evaluated in vivo in 21 patients with a density of >10(4) CFU/cm(2) and in vitro. Skin sites were treated twice daily for 4 days with the active drug or a corresponding control. Quantification of S. aureus was done daily during therapy as well as 3 days thereafter. The severity of the lesions was rated by a regional SCORAD. RESULTS: In gentian-violet-treated skin, bacterial density decreased significantly in lesional (p < 0.001) and unaffected skin (p < 0. 001). Bacterial densities did not decrease during therapy with glucocorticosteroid or liquor carbonis detergens but dropped afterwards. All therapeutics reduced the severity score, reduction being greatest for the glucocorticosteroid and lowest for liquor carbonis detergens. In vitro, a high antibactericidal efficacy was demonstrated only for gentian violet. CONCLUSIONS: Antibacterial therapy with gentian violet not only reduces S. aureus dramatically, but also reduces the severity of the eczema. Reduction of S. aureus after therapy with glucocorticosteroids and LCD seems to be secondary to improvement of the skin condition.

Administration, Topical↗

Infection chains and evolution rates of hepatitis B virus in cardiac transplant recipients infected nosocomially.

Following an outbreak of hepatitis B virus (HBV) infection amongst immunosuppressed transplant recipients, the complete sequences of the HBV-DNA isolated from nine of the affected patients were determined. The DNA sequences were found to differ from each other by a maximum of three nucleotides and belonged to the same serotype (ayw3). By contrast, the sequences differed by 18 nucleotides from the most similar HBV-DNA sequence published, indicating a common source of infection. The infection chains that have been constructed according to the base differences between the DNAs agreed well with those previously established on the basis of epidemiological data [Drescher et al. (1994) Journal of Hospital Infection 26:81-92]. At least two HBV populations, differing by one or two nucleotides, were detected in four patients, and coexisted for differing periods of time. Mutations of the core and X-peptide were not found. The data were used to calculate evolution rates of HBV DNA, both for HBV persisting within a patient and for infection chains. The rates obtained were of the same order as described previously for immunocompetent patients, indicating that the immunosuppressive medication did not influence the evolution rate. However, the evolution rate was found to decrease with increasing evolution time.

Cross Infection↗

Spontaneous pinwheel annihilation during visual development.

Neurons in the visual cortex respond preferentially to edge-like stimuli of a particular orientation. It is a long-standing hypothesis that orientation selectivity arises during development through the activity-dependent refinement of cortical circuitry. Unambiguous evidence for such a process has, however, remained elusive. Here we argue that, if orientation preferences arise through activity-dependent refinement of initially unselective patterns of synaptic connections, this process should leave distinct signatures in the emerging spatial pattern of preferred orientations. Preferred orientations typically change smoothly and progressively across the cortex. This smooth progression is disrupted at the centres of so-called pinwheels, where neurons exhibiting the whole range of orientation preferences are located in close vicinity. Assuming that orientation selectivity develops through a set of rules that we do not specify, we demonstrate mathematically that the spatial density of pinwheels is rigidly constrained by basic symmetry principles. In particular, the spatial density of pinwheels, which emerge when orientation selectivity is first established, is larger than a model-independent minimal value. As a consequence, lower densities, if observed in adult animals, are predicted to develop through the motion and annihilation of pinwheel pairs.

Models, Biological↗

[Endocrine orbitopathy: comparison of the long-term result and classification after radiotherapy].

BACKGROUND: This study compares 4 classifications in patients with progressive refractory Graves orbitopathy (GO) and examines their prognostic value in long-term follow-up. PATIENTS AND METHODS: From 1984 to 1994, 60 consecutive patients (49 female, 11 male) received 20 Gy (10 x 2 Gy) radiotherapy with 6 MV Linac photons. Ocular symptoms and functional impairment was evaluated according to 4 GO-classification systems: Werner-, modified ATA- and Stanford-Score and Ophthalmopathy-Index (OI) according to Grussendorf. In addition, all patients noted their subjective response on a linear scale (0 to 100%). RESULTS: Improvement was achieved within 1 year after radiotherapy according to the Werner-Score in 28 (47%) patients in > or = 1 symptom category, according to the modified ATA-score in 48 (80%), the Stanford-score in 47 (78%) and the OI-Score in 55 (92%) patients (reduction of > 2 points). The Werner-Score correlated less to the other scores (coefficient r < 0.5) than the other scores among themselves (r approximately 0.9). The ATA-Score improved in the different symptom categories between 47% (stage VI) and 87% (stage V). The OI-Score was reduced by a mean of 6 points. The patients reached a mean subjective improvement of +70 +/- 25%. Acute or chronic side effects were not observed. In multivariate analysis the "male gender" (p = 0.08), a "symptom duration prior to radiotherapy > 1 year" (p = 0.14) and a "high symptom category" (p = 0.11) indicated a negative prognostic trend. CONCLUSIONS: External radiotherapy is effective for severe, progressive GO after pretreatment. A minimum follow-up of at least 12 months and standardized classification and success criteria are required.

Adolescent↗

Epidermal growth factor, vascular endothelial growth factor and progesterone promote placental development in rat whole-embryo culture.

The development and survival of rat embryos in whole-embryo culture is limited by the lack of any maternal blood circulation in a purely fetal placenta. If the resulting placental insufficiency could be overcome for some time by an increase of the placental exchange area, a prolonged culture period would result and facilitate the development of embryos. In the present study, several attempts to stimulate proliferation and growth of the fetal placenta were made by the addition of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and progesterone to the culture medium. Rat embryos were routinely explanted with their embryonic membranes at 10.5 days of gestation. Decidua, parietal yolk sac, Reichert's membrane and the layer of superficial trophoblastic giant cells were removed. The explants were cultured and gassed continuously for 24 h in rotating plastic tubes containing rat serum, diluted to 50% with modified COON's F12 medium. Either of the two growth factors or progesterone were added to each culture tube and a control group was cultured without any factor. After the addition of each of these factors the stimulatory effect on placental growth was assessed by morphometric evaluation of several placental parameters from semithin cross-sections: On adding each of the factors the whole cross-sectional area of the placenta significantly increased, as did the area of the fetal placental mesenchyme. VEGF also increased the area of the trophoblast, and the area of the blood vessels enclosed within the trophoblast, by an average of 9.4% and 23.6%, respectively. Thus, VEGF treatment resulted in a measurable extension of the exchange area of the fetal placenta.

Animals↗

The layout of orientation and ocular dominance domains in area 17 of strabismic cats.

In the primary visual cortex of strabismic cats, the elimination of correlated activity between the two eyes enhances the segregation of the geniculocortical afferents into alternating ocular dominance domains. In addition, both tangential intracortical fibres and neuronal synchronization are severely reduced between neurons activated by different eyes. Consequently, ocular dominance columns belonging to different eyes are functionally rather independent. We wondered whether this would also affect the organization of orientation preference maps. To this end, we visualized the functional architecture of area 17 of strabismic cats with both optical imaging based on intrinsic signals and double labelling of orientation and ocular dominance columns with [14C]2-deoxyglucose and [3H]proline. As expected, monocular iso-orientation domains had a patchy appearance and differed for the two eyes, leading to a clear segregation of the ocular dominance domains. Comparison of 'angle maps' revealed that orientation domains exhibit a pinwheel organization as in normally reared cats. Interestingly, the map of orientation preferences did not show any breaks at the borders between ocular dominance columns: iso-orientation domains were continuous across these borders. In addition, iso-orientation contours tended to cross the borders of adjacent ocular dominance columns at right angles. These data suggest that the basic relations between the layout of orientation maps and ocular dominance columns are not disturbed by artificial decorrelation of binocular input. Therefore in cat area 17, the orientation map does not seem to be modified by experience-dependent changes of thalamic input connections. This suggests the possibility that use-dependent rearrangement of geniculocortical afferents into ocular dominance columns is due to Hebbian modifications whereby postsynaptic responsivity is constrained by the scaffold of the orientation map.

Animals↗

Measuring the quality of diagnostic hypothesis sets for studies of decision support.

Within medical informatics there is widespread interest in computer-based decision support and the evaluation of its impact. It is widely recognized that the measurement of dependent variables, or outcomes, represents the most challenging aspect of this work. This paper describes and reports the reliability and validity of an outcome metric for studies of diagnostic decision support. The results of this study will guide the analytic methods used in our ongoing multi-site study of the effects of decision support on diagnostic reasoning. Our measurement approach conceptualizes the quality of a diagnostic hypothesis set as having two components summed to generate a composite index: a Plausibility Component derived from ratings of each hypothesis in the set, whether correct or incorrect; and a Location Component derived from the location of the correct diagnosis if it appears in the set. The reliability of this metric is determined by the extent of interrater agreement on the plausibility of diagnostic hypotheses. Validity is determined by the extent to which the index generates scores that make sense on inspection (face validity), as well as the extent to which the component scores are non-redundant and discriminate the performance of novices and experts (construct validity). Using data from the pilot and main phases of our ongoing study (n = 124 subjects working 1116 cases), the reliability of our diagnostic quality metric was found to be 0.85-0.88. The metric was found to generate, on inspection, no clearly counterintuitive scores. Using data from the pilot phase of our study (n = 12 subjects working 108 cases), the component scores were moderately correlated (r = 0.68). The composite index, computed by equally weighting both components, was found to discriminate the hypotheses of medical students and attending physicians by 0.97 standard deviation units. Based on these findings, we have adopted this metric for use in our further research exploring the impact of decision support systems on diagnostic reasoning and will make it available to the informatics research community.

Decision Support Systems, Clinical↗