Biomedical subjects
Publications and source records attributed to B Breuer.
Individualized care, resident assessment by a multidisciplinary team, and rehabilitation enhance functional independence in nursing home residents. Creativity in choosing alternatives to restraints was important in successful restraint reduction. Residents free of restraints had higher ADL levels, were more continent, and sustained fewer serious injuries, all of which are important quality of life indicators.
A broad spectrum of very different institutions is confronted with the problem of sexual child abuse. So far, only a few systematic descriptions of institutional interventions and their impact on sexually abused children exist. In this article, first results are presented of a study investigating "individual and institutional reactions on sexual child abuse'. In dealing with this problem legal provisions are of special importance. The results presented are based on data obtained from questionnaires and qualitative interviews with experts (median of vocation experience: 8 years) in two german cities (berlin/cologne). Questionnaires were filled in by 195 experts from the entire institutional spectrum (counselors, clinical centres, youth welfare departments, public prosecutors, courts of justice, police), of whom 40 additionally took part in a detailed interview. This article focuses on the question, how different institutions handle legal provisions. The use of criminal law exemplarily shows the different impact of legal provisions on the interventions of counselors. The close connection between the assessment of legal interventions and counseling concepts could be shown at the example of the allegedly homogeneous group of specific counselors.
Retinoic-acid mediated differentiation of F9 cells is accompanied by an increased transcription of the histone H1zero gene. This increase is an early response after addition of retinoic acid, suggesting a direct effect of the hormone on transcription of the gene. We show now that the promoter of histone H1zero contains a DNA element, localized 531 base-pairs upstream of the cap site, that is composed of a direct repeat of the sequence PuGGTCA separated by eight base-pairs. This element confers retinoic acid responsiveness to a heterologous thymidine kinase promoter in F9 and HeLa cells. Furthermore, the element forms retarded complexes not only with bacterially expressed retinoic acid receptors (RARs) and retinoid X receptors (RXRs), but also with endogenous F9 receptors. Our results suggest therefore that retinoic acid receptors can control the expression of a chromatin structural gene the expression of which is associated with a differentiated phenotype.
The replacement histone H1(0) of the H1 group, known to interact with general transcription factors, has been found associated with transcriptionally repressed chromatin. Transcription of the gene in F9 stem cells is low but can be stimulated by treating the cells with retinoic acid. Using mutant deletions, we now demonstrate that basal level transcription in F9 cells is mediated by an 80 bp DNA fragment, located 430 bp upstream of the TATA box, which does not include the retinoic acid responsive element (RARE) known to bind retinoic acid receptors and stimulate transcription from an heterologous promoter after retinoic acid treatment. By footprinting, DMS interference, site-directed mutagenesis and UV-cross linking techniques we demonstrate that at least two nuclear factors, with MW of 90,000 and 30,000, bind to the 80 bp fragment and that this binding is necessary for transcription. Furthermore, positioning of this fragment upstream of the HSV-tk gene promoter stimulates transcription 2-3 times over control values, far less than the activity observed for this fragment in the homologous promoter, indicating that full activity of this fragment requires sequences located in the proximal part of the promoter.
The objective of this study was to validate reports on the bilaterality status of breast cancer in first-degree relatives of women with a strong family history of the disease; i.e., women with 1) two first-degree relatives who have, or have had, breast cancer; 2) one first- and one second-degree affected relative; or 3) one first-degree relative with diagnosis of breast cancer before the age of 50 years and/or bilateral breast cancer. We were able to obtain hospital records for 94 affected relatives of 83 patients who agreed to participate in the study. The accounts of these women were compared to the bilaterality status indicated in the hospital records of the affected relatives. Inconsistencies that might have been attributed to incomplete medical records were resolved through personal interviews with the participants, and when indicated, with other family members or the physician of the affected relative. Overall, 89.4% (84/94) of the reports validated in this manner were correct. Participants who reported unilateral breast cancer in a first-degree relative were correct 94.4% (68/72) of the time. Similarly, 94.0% (47/50) of the accounts concerning affected living relatives were accurate, regardless of whether the participant had indicated unilateral or bilateral disease. However, participants who reported bilateral breast cancer in a deceased relative were accurate only 61.5% (8/13) of the time. Incorrect reports were associated with misunderstanding of medical terminology, especially if the participant was young at the time of the diagnosis of her relative.
Intravenous immunoglobulins and serum protein solutions are manufactured from human plasma pools of healthy, screened donors. A step-by-step validation of virus removal and/or inactivation was performed for the manufacturing process, which includes cold ethanol fractionation, beta-propiolactone (beta-PL) treatment, UV irradiation, thermal inactivation and other chemical and physical purification steps. The total viral clearance factors achieved for the entire manufacturing process were by several magnitudes greater than the potential virus load of current plasma pools. Human immunodeficiency virus 1 (HIV-1) infectivity was reduced by > 13.4 log for 7S immunoglobulin, > 15.3 log for IGM enriched immunoglobulin and > 16 log for a 5% serum protein solution. In addition, high clearance rate for a broad spectrum of model viruses was demonstrated for all three blood derivatives being > 23.2 to > 27.8 log for pseudo rabies virus (PSR), > 12.3 to > 22.6 log for vesicular stomatitis virus (VSV) and 6.9-10.6 log for simian virus 40 (SV40). For the beta-propiolactone inactivation step Hepatitis C model viruses, e.g. equine arteritis virus (EAV) and bovine viral diarrhoea virus (BVDV) were also investigated.
We have used two classes of double-expression retroviral vectors for the expression of foreign genetic information in embryonal carcinoma cell lines. The splice-vector pM5neo takes advantage of mutated sequences that mediate an LTR-driven expression in F9 EC cells. The second vector (pXT1 type) uses an internal HSV-tk promoter as the control element for the transcription of the second gene. Genomic analysis of DNA from infected F9 cell lines revealed that most of the proviruses have rearranged upon integration into the host genome. This reorganization always included the nonselected gene and is sequence independent, but depends on the selective pressure applied. No retroviral genomic rearrangements were observed in F9 cells infected with pM5 proviruses carrying only the neo resistance gene. On the contrary, gross rearrangements were found in cells infected with parental pXT1 retroviruses. In both vectors the transcriptional activity was very low. A direct correlation between selective pressure, proviral reorganization, and transcription was observed.
Populations vary in consistency of diets. The precision of estimates (E) of nutrient intake depends both on the ratio (R) of intraindividual to interindividual variances, as well as on the number of days of dietary intake recorded (k). We present baseline data from 872 participants in the Trial of Antihypertensive Interventions and Management (TAIM), a randomized clinical trial of diet and drug treatment for mild hypertension. There is wide variation in R among different demographic groups and for different nutrients. This has implications for the ability to estimate the correlations between the nutrient and a physiologic variable such as blood pressure, as well as for power calculations to compare group means on nutrient intake. For example, to achieve the same degree of precision (E = 0.80) in estimating the correlation between sodium intake and blood pressure for whites in New York, 7 days of food records would be required, compared to 2 days for whites in Alabama. Tables are presented indicating within- and between-person variances for different groups and different nutrients. Methods of calculating E, determining k, and calculating samples size are provided. Investigators designing nutritional epidemiologic studies should take into account ratios of intraindividual to interindividual variances of different population subgroups and different nutrients in order to determine the number of daily food records that must be obtained and the sample size for group comparisons.
Basal level transcription of the mouse histone H1(0) gene is mediated by 531 base pairs of the promoter region. Deletion of the most distal upstream 80 bp of this fragment reduces transcription to very low values. By in vitro footprinting we demonstrate now that multiple factors bind to the DNA fragment localized between the 80 bp and the cap nucleotide. In addition to the presence of motifs for the binding of SP1, H1-box, H4TF-2 and TATA-box-factors, other not yet described protein-binding elements were identified. Internal deletions in the wild type promoter enclosing these motifs strongly restrict transcription. Furthermore, when one of these motifs was modified by site-directed mutagenesis a strong impairment of transcription followed. Thus for basal level transcription, in addition to the 80 bp distal fragment, cis-acting elements localized in the 450 bp proximal promoter region are required.
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The charts of 1351 patients undergoing cholecystectomy at our institutions from 1985 through 1989 were reviewed retrospectively to evaluate the indications for and the success of intraoperative cholangiography. A total of 800 patients underwent intraoperative cholangiography. They were divided into two groups based on the absence (CR-) or presence (CR+) of clinical and/or operative criteria suggestive of the existence of common bile duct stones. Intraoperative cholangiography in CR- patients was of limited benefit, being negative (normal) in 95.7%, true-positive (abnormal) in 3.3%, and false-positive in 1%. False-positive intraoperative cholangiography resulted in unnecessary common bile duct explorations. Intraoperative cholangiography in CR+ patients proved useful, avoiding unnecessary common bile duct exploration in 55%. In those select CR+ patients with palpable common bile duct stones or cholangitis, little additional information was gained by the intraoperative cholangiography. We conclude that routine screening intraoperative cholangiography in CR- patients be reconsidered, as should the use of intraoperative cholangiography in CR+ patients with a palpable common bile duct stone or cholangitis. Intraoperative cholangiography in the remainder of CR+ patients proved beneficial and should be continued.
In F9 cells transformed with bovine papillomavirus type 1 (BPV-1) sequences two different phenotypes can be recognized. One cell type shows the characteristics of the parental stem cell line, whereas the other comprises cells with spindle-like morphology that do not adhere to each other, similar to retinoic acid-treated F9 embryonal carcinoma cells. The phenotypically altered cells plate more efficiently than the stem cells, grow well in soft agar and show an extended lifespan in the differentiated stage. Both types of cells contain BPV-1 DNA sequences as episomes, but only the non-stem-like cells have RNA transcripts for the unspliced E5 reading frame as well as for the spliced E6/E4.
A novel large heterodimeric dermatan sulfate proteoglycan with core proteins of 460 and 300 kDa, respectively, had been described as a secretory product of human fetal skin fibroblasts (Breuer et al., J. Biol. Chem. 266, 13224-13232 (1991)). Pulse-chase experiments showed a preferential association of the proteoglycan with the cell membrane. Immunogold labeling indicated its localization in fibrils on the cell surface as well as in fibrillar extensions from the cell body. Immunofluorescence studies yielded a fibrillar and punctate staining pattern which was also seen in cultured human and porcine endothelial cells. Dot-like structures were observed in transformed human keratinocytes. Various immunocytochemical double-labeling experiments indicated a remarkable colocalization of the proteoglycan with fibronectin, laminin, perlecan, and type IV collagen whereas only occasionally a colocalization with chondroitin-6-sulfate was found. No evidence for an enrichment of the proteoglycan in vinculin-containing structures was obtained. These results suggest that the proteoglycan is a widely distributed macromolecule which can associate with basement membrane components. Preliminary findings in rat cornea supported this conclusion.
Human skin fibroblasts express, in addition to versican, a second large chondroitin sulfate/dermatan sulfate proteoglycan, which has been investigated with the aid of a specific antiserum in cultures of fetal fibroblasts. Its core protein, obtained after chondroitin ABC lyase treatment, exhibits an apparent molecular mass of about 740 kDa in the absence of a reducing agent whereas reduction produces two core proteins of 460 and 300 kDa, respectively. Both subunits carry one or very few dermatan sulfate chains of about 20 kDa which are of similar chemical composition irrespective of the type of subunits to which they are attached. Tryptic peptide maps of [35S]methionine-labeled core proteins indicated that both subunits are related neither to each other nor to versican, suggesting that the proteoglycan exists predominantly as a heterodimeric molecule. It is insensitive to collagenase and does not interact with hyaluronan. Pulse-chase experiments suggested that the core proteins are different gene products. Dimerization begins soon after core protein synthesis but requires more than 2 h for completion. Glycosaminoglycan synthesis occurs immediately prior to secretion. A small proportion of both subunits may be secreted in form of a monomeric proteoglycan. The heterodimeric proteoglycan is a major proteoglycan species of fetal fibroblasts. The secreted product represents 10-20% of [35S]methionine and about 5-10% of [35S]sulfate incorporated into secreted proteoglycans.
The teratocarcinoma stem cell line F9 has been widely used as a model for the analysis of molecular mechanisms associated with differentiation. This cell line has been considered to be nullipotent and able to differentiate into endodermal-like derivatives upon treatment with retinoic acid. Nevertheless, under definite culture conditions, F9 cells are able to differentiate into derivatives of all three germ layers. The F9 cells express characteristics of early mouse embryonal cells and possess all repression factors known to be present in cells of the early mouse embryogenesis. Induction of differentiation can be achieved not only by adding chemical agents to the culture medium but also by transfection of several oncogenic sequences. In somatic cell genetic experiments, immortalized, differentiated F9-like cells have been shown to express dominantly genes responsible for the appearance of the differentiated phenotype.
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Human osteosarcoma cells express a 78-kDa proteoglycan core protein to which an asparagine-bound oligosaccharide, O-glycosidically linked oligosaccharides and probably only a single chondroitin 6-sulfate chain of 29-kDa are bound. Prior to O-glycosylation, the N-glycosylated core protein exhibits a mass of 83 kDa. Upon digestion of the secreted proteoglycan with chondroitin ABC lyase a mature core protein with an apparent molecular mass of 106 kDa is obtained. Smaller amounts of core proteins of 101 and 115 kDa can be detected occasionally. The glycosaminoglycan composition and the relative molecular mass of the glycosaminoglycan chain distinguish this proteoglycan, tentatively named proteoglycan 100 (PG-100), from biglycan (small proteoglycan I) and decorin (small proteoglycan II) which are also expressed by osteosarcoma cells. An antiserum against PG-100 shows partial cross-reactivity with decorin, but in contrast to the latter proteoglycan it does not bind to type I collagen fibrils. PG-100 is not a unique product of osteosarcoma cells. It has also been found in the secretions of human skin fibroblasts.