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Biomedical subjects

M Claussen

Publications and source records attributed to M Claussen.

At least 19 recordsLinked to original sources

[Endoscopic ultrasound-guided fine-needle aspiration in pulmonary medicine].

Endoscopic ultrasound-guided fine-needle aspiration has significantly increased the capacity of pulmonary diagnostic procedures. Since this method was introduced, 1212 examinations have been performed at two centres of pulmonary medicine. Data on indications, procedures, findings, diagnostic yield and complications have been recorded. This paper describes the experiences thus gained regarding the possibilities and limitations of the method and assesses the current significance of the technique in pulmonary medicine according to previous studies. In primary diagnosis of mediastinal tissue alterations and in staging of malignant diseases the method offers a low-complication diagnostic measure which has a seminal impact on therapy in many cases, even though in daily practise the diagnostic accuracy of published studies is not always attained.

Biopsy, Fine-Needle↗

Extraction and amplification of authentic DNA from ancient human remains.

A total of 36 ancient human remains from 12 individuals (three tooth/bone samples each) and one sample each of three individuals from the newest time was typed in a blind study using the amelogenin sex test. Prior to this molecular sex determination the sex of the individual was determined morphologically. The success rate of the amelogenin amplifications was >90%. For every individual an unambiguous molecular sex typing result was obtained. Furthermore, the morphological and molecular sex determinations were in accordance with each other, giving evidence for the authenticity and ancient origin of the polymerase chain reaction (PCR) amplifications.

Amelogenin↗

Virulence factors of Enterococcus faecalis and Enterococcus faecium blood culture isolates.

Known and potential virulence factors of enterococcal blood culture isolates were studied using 89 Enterococcus faecalis and 24 Enterococcus faecium isolates. The prevalence of the respective factors was (Enterococcus faecalis vs. Enterococcus faecium): hemolysin 16% vs. 0%, gelatinase 55% vs. 0%, aggregation substance 63% vs. 13%, lipase 35% vs. 4%, hemagglutinin 97% vs. 0%. Deoxyribonuclease was not detected in any isolate. The study showed that hemagglutinin and lipase may represent additional virulence factors of Enterococcus faecalis but not Enterococcus faecium. The significance of these factors in the pathogenesis of enterococcal infection needs to be elucidated in further studies.

Bacterial Proteins↗

Functional modules in ribosomal protein L5 for ribonucleoprotein complex formation and nucleocytoplasmic transport.

Ribosomal protein L5 forms a small, extraribosomal complex with 5 S ribosomal RNA, referred to as the 5 S ribonucleoprotein complex, which shuttles between nucleus and cytoplasm in Xenopus oocytes. Mapping elements in L5 that mediate nuclear protein import defines three separate such activities (L5-nuclear localization sequence (NLS)-1, -2, and -3), which are functional in both oocytes and somatic cells. RNA binding activity involves N-terminal as well as C-terminal elements of L5. In contrast to the full-length protein, none of the individual NLSs carrying L5 fragments are able to allow for the predominating accumulation in the nucleoli that is observed with the full-length protein. The separate L5-NLSs differ in respect to two activities. Firstly, only L5-NLS-1 and -3, not L5-NLS-2, are capable of promoting the nuclear transfer of a heterologous, covalently attached ribonucleoprotein complex. Secondly, only L5-NLS-1 is able to bind strongly to a variety of different import receptors; those that recognize L5-NLS-2 and -3 have yet to be identified.

Amino Acid Sequence↗

The influence of vegetation-atmosphere-ocean interaction on climate during the mid-holocene

Simulations with a synchronously coupled atmosphere-ocean-vegetation model show that changes in vegetation cover during the mid-Holocene, some 6000 years ago, modify and amplify the climate system response to an enhanced seasonal cycle of solar insolation in the Northern Hemisphere both directly (primarily through the changes in surface albedo) and indirectly (through changes in oceanic temperature, sea-ice cover, and oceanic circulation). The model results indicate strong synergistic effects of changes in vegetation cover, ocean temperature, and sea ice at boreal latitudes, but in the subtropics, the atmosphere-vegetation feedback is most important. Moreover, a reduction of the thermohaline circulation in the Atlantic Ocean leads to a warming of the Southern Hemisphere.

Journal Article↗

Biodegradation of phenol and p-cresol by the hyphomycete Scedosporium apiospermum.

A hyphomycete with the ability to utilize phenol and p-cresol as carbon and energy source was isolated from soil and subsequently identified as Scedesporium apiospermum. The identification of degradation metabolites and the detection of the corresponding catabolic enzymes in crude extracts enabled us to propose different pathways for the degradation of both phenol and p-cresol in this organism. Generally, the catabolism proceeded via three different dihydroxylated intermediates (catechol, hydroxyhydroquinone and protocatechuate) which were intradiolically cleaved by the corresponding inducible dioxygenases and further catabolized via the 3-oxoadipate pathway.

Biodegradation, Environmental↗

Leukodystrophy incidence in Germany.

Through a survey of all departments of pediatrics, neurology and neuropathology in Germany, we calculated the incidence of all major forms of leukodystrophy. Only diagnoses based on specific biochemical tests in association with typical findings and/or neuroradiologically proven white matter involvement were accepted. In accordance with these strict criteria, 617 cases of leukodystrophy were found (incidence of all forms: app. 2.0/100,000). Minimal incidence was estimated at 0.8/100,000 for adrenoleukodystrophy/adrenomyeloneuropathy (ALD/AMN), 0.6/100,000 for metachromatic leukodystrophy (MLD), and 0.6/100,000 for Krabbe disease. Thus ALD/AMN is apparently underdiagnosed in Germany. A considerable proportion of leukodystrophies could not be classified in spite of adequate diagnostic procedures in experienced centers.

Adolescent↗

[Intracranial pressure monitoring in patients with severe craniocerebral injury].

After severe head injury intracranial pressure (ICP) must be measured continuously for management to assess and maintain the cerebral perfusion. Therefore in our hospital epidural transducers are used. To prove the efficiency of this method in a 12-month period the clinical courses of 23 patients with intracranial pressure transducers were analysed retrospectively. Eighteen patients survived, 5 of them without residuals, 13 with residuals and 2 remained in coma. In 14 patients secondary rises of intracranial pressure were observed between days 3 and 6 post injury. The mean ICP value of the survivors revealed 25 mm Hg. whereas the expired showed 60 mm Hg. In 17 patients the measurements were considered as reliable, 6 measurements were not reliable, which included 1 of the 5 patients who died. One transduce was displaced, another one showed a hemorrhage at the drill hole. There was no infection.

Adolescent↗

Airway responsiveness to sulfur dioxide in an adult population sample.

We determined the prevalence of airway hyperresponsiveness to sulfur dioxide (SO2) in an adult population sample of 790 subjects 20 to 44 yr of age. Subjects were drawn randomly from the population of Hamburg, Northern Germany, within the framework of the European Community Respiratory Health Survey. In addition, we analyzed the relationship between SO2 responsiveness and a number of risk factors, such as a history of respiratory symptoms, methacholine responsiveness, and atopy derived from skin-prick test results. SO2 inhalation challenges were performed during isocapnic hyperventilation at constant rate (40 L x min(-1), for 3 min) with doubling concentrations of SO2 up to a maximum concentration of 2.0 ppm. If subjects achieved a 20% decrease in FEV1 from baseline during the challenge, they were considered to be hyperresponsive to SO2. The raw prevalence of SO2 hyperresponsiveness within the population sample studied was 3.4% (95% confidence interval [CI]: 2.3 to 5.0%). Adjustment for nonparticipation led to an estimated prevalence of SO2 hyperresponsiveness of 5.4%. Among subjects with hyperresponsiveness to methacholine, 22.4% (95% CI: 20.1 to 25.3) demonstrated hyperresponsiveness to SO2. There was no significant correlation between the degrees of hyperresponsiveness to methacholine and SO2. Predictors of a positive SO2 response were hyperresponsiveness to methacholine (p < 0.0001), a positive history of respiratory symptoms (p < 0.05), and a positive skin-prick test to at least one common allergen (p < 0.05). We conclude from these data that airway hyperresponsiveness to SO2 can be found in about 20 to 25% of subjects within the 20- to 44-yr age range who are hyperresponsive to methacholine.

Adult↗

Proteolysis of insulin-like growth factors (IGF) and IGF binding proteins by cathepsin D.

Various proteinases have been postulated to function in limited proteolysis of insulin-like growth factor binding proteins (IGFBPs) contributing to the regulation of IGF bioavailability. In this study, we report on the in vitro degradation of IGFs and IGFBPs by the purified acidic aspartylprotease cathepsin D that has been shown to proteolyze IGFBP-3. Recombinant human [125I] IGFBP-1 to -5 were processed by cathepsin D to fragments of defined sizes in a concentration dependent manner, whereas IGFBP-6 was not degraded. Ligand blotting revealed that none of the IGFBP-1 or -3 fragments formed by cathepsin D retain their ability to bind IGF. By N-terminal sequence analysis of nonglycosylated IGFBP-3 fragments produced by cathepsin D, at least four different cleavage sites were identified. Some of these cleavage sites were identical or differed by one amino acid from sites used by other IGFBP proteases described. The IGFBP-3 and -4 cleavage sites produced by cathepsin D are located in the nonconserved central region. IGF-I and -II, but not the unrelated platelet-derived growth factor BB, were degraded by cathepsin D in a time and concentration-dependent manner. We speculate that the major functional site of cathepsin D is intracellular and may be involved 1) in the selected clearance either of IGFBP or IGFs via different endocytic pathways or 2) in the general lysosomal inactivation of the IGF system.

Amino Acid Sequence↗

Prevalence of respiratory symptoms, bronchial hyperresponsiveness and atopy among adults: west and east Germany.

The prevalence of respiratory symptoms, atopic sensitization and bronchial hyperresponsiveness was compared in a random sample of adults, 20-44 yrs of age, in two cities in West and East Germany, Hamburg and Erfurt, respectively. There were much higher levels of outdoor air pollution due to sulphur dioxide and suspended particulates in Erfurt, and major differences in living conditions during the last 40 yrs. Within the European Respiratory Health Survey, a short questionnaire was answered by 3,156 (80% response rate) subjects in Hamburg and 3,272 (74%) in Erfurt. A subset of responders to the short questionnaire completed a long questionnaire, spirometry, methacholine or bronchodilator test, skin test, and total and specific immunoglobulin E (IgE) measurements, with a total number of 1,159 participants in Hamburg and 731 in Erfurt. Six out of 8 questions on respiratory symptoms and diagnoses were answered in the affirmative more frequently in Hamburg than in Erfurt. In Hamburg, mean forced expiratory volume in one second (FEV1)% of predicted was 105 vs 107% in Erfurt (p < 0.0001), and bronchial hyperresponsiveness was more frequently observed in Hamburg than in Erfurt (25 vs 19%; p < 0.05). Atopic sensitization was more prevalent in Hamburg than in Erfurt regarding the results of skin tests against grass pollen (24 vs 19%; p < 0.05), birch pollen (19 vs 8%; p < 0.0005), cat (10 vs 2%; p < 0.0005), and Dermatophagoides pteronyssinus (14 vs 10%; p < 0.05). This was reflected by the prevalences of positive specific IgE values, which were higher in Hamburg than in Erfurt for grass (26 vs 20%; p < 0.05), birch (20 vs 10%; p < 0.0005) and cat (12 vs 8%; p < 0.05). In Hamburg, compared to Erfurt, there was: a lower mean number of siblings (p < 0.005); a higher degree of childhood and current exposure to environmental tobacco smoke (p < 0.005); and a higher frequency of fitted carpets and reported mould or mildew inside the house (p < 0.005). Therefore, these data may support the hypothesis that childhood factors and exposure to indoor allergens and irritants may have been more relevant for the development of asthma and atopy than the potential long-term exposure to high concentrations of sulphur dioxide and particulate matter.

Adult↗

Immunohistochemical localization of insulin-like growth factor binding protein-1, -3 and -4 in human fetal tissues and their analysis in media from fetal tissue explants.

The actions of insulin-like growth factor (IGF) II that are important in the regulation of fetal growth and development, are modulated by IGF binding proteins (IGFBPs). We have determined the cellular distribution of IGF-II and IGFBP-1, -3 and -4 in 12-week gestation human fetal tissues using immunocytochemistry. IGF-II immunostaining was found in all organs examined, with strongest immunoreactivity in spinal ganglia, tubular cells of the mesonephros and peri- and epidermal layers of the skin. The immunoreactivity distribution of all IGFBPs was similar to that of IGF-II except lung, hepatic parenchyma, fibrocytes of connective tissue and cells of the growth plate in the cartilage. When conditioned media from skin, liver, lung and kidney explants were analyzed, phosphorylated IGFBP-1 was only detected in liver samples whereas IGFBP-3 was found in all media. Weak immunoreactivity of IGFBP-4 was seen in media from lung tissue. To determine whether proteolytic degradation of IGFBPs were responsible for the different IGFBP levels, cell-free conditioned media were incubated with recombinant human IGFBPs. At neutral pH only proteolysis of IGFBP-4 was observed in media from skin and lung tissue. Upon acidification of the medium samples, IGFBP-1 fragments were formed in skin-derived medium and IGFBP-3 was cleaved by medium from lung and kidney tissue. Acid-activated proteolytic activity against IGFBP-4 was found in the media from lung and liver. These findings suggest that IGFBP proteases may be important in locally defining the concentrations of IGFBPs and contribute to tissue-specific growth response to IGFs.

Antibodies, Monoclonal↗

Proteolysis of IGFBPs by cathepsin D in vitro and in cathepsin D-deficient mice.

Affinity-purified lysosomal protease cathepsin D cleaved recombinant human IGFBP-1 to -5 in fragments of defined sizes, while IGFBP-6 was not degraded. To assess the role of cathepsin D for proteolytic processing of IGFBP in vivo, serum from cathepsin D-deficient mice and conditioned media from cathepsin D-deficient fibroblasts and organ explants were analyzed. No differences for the pattern and level of IGFBPs were detected. When conditioned media from fibroblasts were incubated at acid pH, proteolysis of IGFBP-1 and -4 was observed only in media derived from cathepsin D-expressing cells. Additional experiments showed that the proteolysis of IGFBP-4 is mediated by cathepsin D and not by a protease activated by cathepsin D. The IGFBP-4 degrading activities in media from organ explants from cathepsin D-deficient mice were found to be sensitive to inhibitors of aspartyl and cysteine proteases. The data indicate that different classes of acid pH-dependent proteases can contribute to the regulation of IGFBP-4 abundance.

Animals↗

Regulation of insulin-like growth factor (IGF)-binding protein-6 and mannose 6-phosphate/IGF-II receptor expression in IGF-IL-overexpressing NIH 3T3 cells.

Insulin-like growth factor II (IGF-II)-overexpressing NIH 3T3 cells were used to examine regulation of insulin-like growth factor binding protein (IGFBP) and mannose 6-phosphate (M6P)/IGF-II receptor expression. Ligand blot analysis of conditioned media indicated a predominant IGFBP of 26-28 kilodaltons the abundance of which is 3- to 10-fold higher in media of IGF-II-overexpressing cells. The IGFBP level in control cell medium was increased by incubation in the presence of IGF-II, IGF-I, and mutant IGF-II forms with reduced affinities for IGF-I or M6P/IGF-II receptors. Further proof that IGF-II regulated the IGFBP was obtained by incubation of IGF-II overexpressing cells in the presence of antisense IGF-II oligomers or anti-IGF-II antibodies, which resulted in significant reduction of the IGFBP in conditioned medium. Mouse IGFBP-6 mRNA expression was increased in IGF-II-overexpressing or IGF-II-treated control cells. The IGFBP contained O-linked carbohydrate residues and was recognized by an antiserum to rat IGFBP-6. To determine whether IGFs were influencing proteolytic degradation of IGFBPs, cell-free conditioned media were incubated at 37 C with recombinant human IGFBPs. At neutral pH proteolysis of IGFBP-5 occurred during incubation in conditioned media from control and IGF-II-overexpressing cells. Upon acidification of the medium samples, only the degradation of IGFBP-6 was prevented in IGF-II-overexpressing cell-conditioned medium.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗

Proteolysis of insulin-like growth factor binding protein-5 by pregnancy serum and amniotic fluid.

Incubation of iodinated recombinant human insulin-like growth factor binding protein (rhIGFBP)-5 with pregnancy serum or amniotic fluid resulted in the formation of 22- and 15 kDa fragments. Non-pregnancy serum did not contain IGFBP-5 proteolytic activity. Size fractionation revealed the proteolytic activity both in serum and amniotic fluid in a > 100 kDa fraction which co-eluted in gel filtration with proteins of approx. 200 kDa. The IGFBP-5 protease activity was inhibited by EDTA, phenanthroline and PMSF. The formation of proteolytic fragments was also observed using 125I labeled rhIGFBP-3 and -4 but not with rhIGFBP-1 or -6 as substrate. The data demonstrate that pregnancy serum and amniotic fluid contain a very similar cation-dependent serine protease which degrades IGFBP-3, -4 and -5.

Amniotic Fluid↗