Biomedical subjects
Publications and source records attributed to J Schreiber.
We report on the case of a 77-year old man in whom a lipoma caused occlusion of the lingular bronchus with consecutive dystelectasis. The lipoma was resected via the bronchoscope with a hot snare. The incidence, clinical characteristics and treatment of endobronchial lipomas are described.
We report on the case of a 40-year old patient with extreme neurofibromatosis with severe kyphoskoliosis and deformation of the thorax. The patient died from malignant transformation which occurred multifocally with extensive pulmonary metastases. The well-known thoracic manifestations of neurofibromatosis are reviewed.
The diagnostic value of the lymphocyte transformation test (BeLT) and the intracutaneous skin test with berylliumsulfate was addressed in 13 patients with chronic berylliosis, and 15 individuals with occupational exposure. Additionally, patients with sarcoidosis (n = 21), tuberculosis (n = 14) and healthy controls (n = 25) were tested with BeLT and yielded negative results. In chronic berylliosis the BeLT was positive in 10/13. In 3/13 the BeLT was negative, but the skin test positive. 6/15 exposed individuals exhibited a positive BeLT. The time course of the skin test differed markedly between the individual berylliosis patients. Typical granulomas were present in 4/10 cases. In 9 exposed individuals BeLT tested negative. Additionally, skin tests were negative in 7 exposed patients, however, unspecific skin reactions were observed in 3 cases. The diagnostic value of Beryllium IT requires further investigation. At present, BeLT appears to be a suitable test to prove beryllium sensitisation.
Members of the GCM family of transcription factors contain a DNA binding domain unrelated to any other known DNA binding domain and bind to a DNA sequence motif not recognized by any other known transcription factor. Here we show that positions 2, 3, 6 and 7 of the 5'-ATGCGGGT-3' motif are particularly important for DNA binding and that methylation of several G residues on the upper strand, but not on the lower strand, interfered with binding of GCM proteins. No differences were detected between the DNA binding of Drosophila GCM and mammalian mGCMa. Alanine scan mutagenesis of the DNA binding domain of mGCMa identified the three conserved amino acids K74, C76 and C125 as being essential for DNA binding. Conserved cysteine residues were also found to be important for maintaining the overall integrity of the DNA binding domain and for mediating redox sensitivity of DNA binding. These cysteine residues are arranged in a symmetrical structure that bears no resemblance to other cysteine-containing structures, such as zinc fingers. In agreement with this, DNA binding of mGCMa was not dependent on zinc ions. Our results give insights into the exact nature of the GCM binding sites expected in target genes and point to a role for redox regulation in the function of GCM proteins.
We evaluated the use of a novel three-dimensional ultrasound imaging device in patients with various head and neck lesions. The investigated system was found to be a valuable adjunct to conventional ultrasound in head and neck evaluations. A disadvantage of the three-dimensional system was the need for expensive technical equipment.
We report on the efficiencies of structurally different but well defined multivalent sLex-ligands (di- and trivalent sLex-peptides and sLexbearing liposomes) to block receptor mediated HepG2-cell binding. Using three types of binding assays with distinct receptor accommodations (soluble anti-sLexmonoclonal antibody CSLEX1, immobilized E-selectin, activated HUVECs), we quantified considerable differences of the inhibition efficiencies for the same multivalent sLex-ligands. Compared to the monovalent sLexthe inhibition powers of both (sLex)2-peptides and (sLex)3-peptides were enhanced up to 50-fold for cell binding to the soluble antibody, and that of sLex-liposomes by 7 orders of magnitude. Directed to immobilized E-selectin the inhibition activity was enhanced only 3-fold for (sLex)2-peptides, 10-fold for (sLex)3-peptides but 5 orders of magnitude for sLex-liposomes, respectively. Further decrease of the inhibition efficiencies of glycoligands prepared was observed for cell binding to activated HUVECs. Compared to monovalent sLexwe measured relative efficiencies of 1 for (sLex)2-peptides, of 2 for (sLex)3-peptides but about 20,000 for sLex-liposomes. We concluded that the multivalency of the sLex-ligands prepared is an essential but not sufficient precondition for a high inhibition potency. Additionally, structural properties of the inhibitors determine their binding behavior, which must be considered for the design of potential therapeutic probes.
A 51-year old woman developed hypersensitivity pneumonitis to spinach powder, which is used as a food dye. The diagnosis was confirmed by demonstration of IgG2-antibodies in the patient's serum to distinct bands of spinach extract by Western blotting. Furthermore an exposure test with the natural allergen was positive. Severe disease with fever, chills and dyspnoea developed after inhalation of native spinach powder. Arterial pO2 dropped significantly and pulmonary function tests showed severe restrictive impairment and reduction of diffusion capacity. Leucocyte count and the serum concentrations of the cytokines TNF alpha and IL6 and of the soluble IL2-receptor rose significantly in peripheral blood, whereas the concentration of neopterine did not change. 24 hours after exposure bronchoalveolar lavage showed an increase of neutrophils. In lung parenchyma mononuclear interstitial infiltrates and an epitheloid cell granuloma were seen.
Class III POU proteins are prominent regulators of neural development. Tst-1/Oct6/SCIP, for instance, is essential for terminal differentiation of myelinating Schwann cells in the peripheral nervous system. Although Tst-1/Oct6/SCIP is also expressed in the myelin forming oligodendrocytes of the central nervous system, targeted deletion of Tst-1/Oct6/SCIP failed to reveal a gross alteration of myelination in the central nervous system. To better understand this apparent discrepancy, we examined the expression of POU proteins in both cultured primary oligodendrocytes and in the oligodendrocyte-like CG-4 cell line. These cells expressed Tst-1/Oct6/SCIP, Brn-1, and Brn-2 in significant amounts, indicating that Brn-1 and Brn-2 might have the capacity to compensate loss of Tst-1/Oct6/SCIP. We show that Tst-1/Oct6/SCIP, Brn-1, and Brn-2 were all down-regulated during the early phases of oligodendrocyte development both on RNA and protein level. All three POU proteins exhibited similar DNA binding characteristics. When promoters consisting of a single POU protein-binding site adjacent to a TATA box were used as reporters in transient transfections, Brn-1 proved to be a weaker transcriptional activator than Tst-1/Oct6/SCIP. In agreement with this, we found the transactivation domain of Brn-1, which we mapped between amino acids 119 and 237, significantly weaker than the transactivation domain of Tst-1/Oct6/SCIP. Taken together, our data imply a partial, but not complete redundancy between POU proteins in oligodendrocytes.
OBJECTIVES: To determine the effect of regular prophylactic inhaled corticosteroids on wheezing episodes associated with viral infection in school age children. DESIGN: Randomised, double blind, placebo controlled trial. SETTING: Community based study in Southampton. SUBJECTS: 104 children aged 7 to 9 years who had had wheezing in association with symptoms of upper and lower respiratory tract infection in the preceding 12 months. INTERVENTIONS: After a run in period of 2-6 weeks children were randomly allocated twice daily inhaled beclomethasone dipropionate 200 micrograms or placebo through a Diskhaler for 6 months with a wash out period of 2 months. Children were assessed monthly. MAIN OUTCOME MEASURES: Forced expiratory volume in 1 second (FEV1); bronchial responsiveness to methacholine (PD20); percentage of days with symptoms of upper and lower respiratory tract infection with frequency, severity, and duration of episodes of upper and lower respiratory symptoms and of reduced peak expiratory flow rate. RESULTS: During the treatment period there was a significant increase in mean FEV1 (1.63 v 1.53 1; adjusted difference 0.09 1 (95% confidence interval 0.04 to 0.14); P = 0.001) and methacholine PD20 12.8 v 7.2 mumol/l; adjusted ratio of means 1.7 (1.2 to 2.4); P = 0.007) in children receiving beclomethasone dipropionate compared with placebo. There were, however, no significant differences in the percentage of days with symptoms or in the frequency, severity, or duration of episodes of upper or lower respiratory symptoms or of reduced peak expiratory flow rate during the treatment period between the two groups. CONCLUSIONS: Although lung function is improved with regular beclomethasone dipropionate 400 micrograms/day, this treatment offers no clinically significant benefit in school age children with wheezing episodes associated with viral infection.
Absence or presence of glial cells missing (GCM) in cells of the developing nervous system of Drosophila decides over their future fate as neurons or glia with only those cells turning into glia that express GCM. To understand how GCM exerts its function we performed a detailed structure-function analysis. Using fusions between the DNA binding domain of the yeast GAL4 protein and GCM, we detected a transactivation function within the C-terminal part of GCM. In addition to this transactivation domain we mapped a sequence-specific DNA-binding domain within the N-terminal part of the GCM protein in close proximity to a bipartite nuclear localization signal. Binding site selection assays determined the motif 5'-AT(G/A)CGGGT-3' as the preferred binding site for GCM. Both the lack of homology to known proteins and the novel DNA binding specificity indicate that GCM contained a new type of DNA-binding domain. In transiently transfected cells, GCM also activated transcription from promoters consisting of the newly identified GCM-binding site and a TATA box. Thus, GCM is a novel type of transcription factor involved in early gliogenesis.
Indirect tests of bronchial responsiveness to agents such as adenosine 5'-monophosphate (AMP) or bradykinin might be more specific markers of a therapeutic responses to anti-inflammatory treatment than a test of direct responsiveness to agents such as methacholine. In children selected from the community on the basis of mildly symptomatic wheeze, we compared in a randomized, double-blind study design the effect of 400 micrograms/day of beclomethasone dipropionate (BDP) or placebo on three separate ways of provoking bronchial responsiveness, using methacholine, bradykinin, and AMP as the provoking agents. Following pretreatment bronchial challenges, 29 children received paired monthly methacholine and AMP challenges for 3 months, while for the same period another 33 children received paired monthly methacholine and bradykinin challenges. Compared with placebo-treated subjects, FEV1 increased significantly in the children receiving BDP. This improvement was observed in those randomized to either the AMP challenge or the bradykinin challenge. In children challenged with AMP, the PD20 AMP increased significantly after 1 month and 2 months of BDP therapy when compared with placebo, while under similar conditions the PD20 methacholine was not significantly affected. In children challenged with bradykinin, BDP therapy did not significantly alter either the PD20 bradykinin or PD20 methacholine. We conclude that a bronchial challenge with AMP appears to be a more sensitive predictor of response to anti-inflammatory treatment than either methacholine or bradykinin.
Krox proteins are important regulators of development and terminal differentiation. Using the rat glial progenitor cell line CG-4 as a model system for oligodendrocyte differentiation, we show that on the RNA level Krox-24 is the predominant member of the Krox family in these cells. Similar results were also obtained on the protein level as the major Krox protein from CG-4 cell extracts reacted specifically with an antibody against Krox-24. Whereas Krox-24 RNA and protein were abundant in undifferentiated CG-4 cells, a dramatic decrease in expression was detected after a 3-5-day period of differentiation during which we observed a reciprocal increase in the levels of myelin basic protein expression. Importantly, regulation of Krox-24 expression was very similar in CG-4 cells and primary oligodendrocyte cultures. When expression of Krox-24 in differentiating CG-4 cells was followed on a closer time scale, we observed a sharp and transient increase in Krox-24 RNA, protein, and DNA binding activity immediately after the onset of differentiation followed by an equally rapid decrease. This expression pattern implicates Krox-24 both in maintenance of the undifferentiated state and in the immediate early phase of differentiation of CG-4 cells and possibly oligodendrocytes.
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BACKGROUND: Currently the diagnosis of tumorous lesions of the carotid bifurcation is the domain of magnetic resonance imaging (MRI) and digital subtraction angiography (DSA). So far, colour Doppler imaging (CDI) has not been playing an important part in this field. The aim of this study was to define the diagnostic value of CDI in the evaluation of these tumours related to the big arteries and to compare the different imaging techniques. PATIENTS AND METHODS: 6 female patients with suspected tumours of the carotid bifurcation were examined with CDI. Additionally 5 MRI examinations and 3 preoperative diagnostic DSA examinations were performed in the same patients. Pathologically, there were 4 typical carotid body tumours, 1 neuroma of the sympathetic trunk and 1 multifocal paraganglioma of the neck. RESULTS: In carotid body tumours we found a characteristic broadening of the bifurcation with shifting of the internal carotid artery posteriorly and laterally and of the external carotid artery anteriorly and medially. The highly vascularized tumour is surrounded by the arteries. This combination of ultrasound findings was absent in cases of sympathetic neuroma and multifocal paraganglioma. No additional information was achieved with MRI and DSA. CONCLUSION: CDI and MRI evaluation revealed the same diagnostic value in cases of vascularised tumours of the carotid bifurcation. CDI proved to be as accurate as DSA in the imaging of the big arteries and their relationship to the tumour, as well as of the small tumour feeding vessels. Therefore DSA may be omitted as an invasive diagnostic tool in the diagnosis of carotid body tumours.
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We undertook a study in Albany, New York, to investigate whether volatile organic compounds (VOCs) were measurable in the blood and in the breathing-zone air of people exposed to gasoline fumes and automotive exhaust. We sampled blood of 40 subjects, placed organic vapor badges on 40 subjects, and obtained personal breathing-zone samples from 24 subjects. We limited this analysis to 19 subjects who wore the organic vapor badges for at least 5 h. VOC levels, as determined by the organic vapor badges, were highly correlated with blood levels of these same compounds. Using detection in blood as the gold standard, we found the badges to be more sensitive than conventional charcoal tube samples in detecting low levels of methyl tert-butyl ether (0.60 vs 0.08), toluene (0.95 vs 0.64), and o-xylene (0.85 vs 0.64). In this study, organic vapor badges provided data on VOC exposure that correlated with blood assay results. These organic vapor badges might provide a convenient means of determining human exposure to VOCs in epidemiologic studies.
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