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Biomedical subjects

E Wagner

Publications and source records attributed to E Wagner.

At least 217 records · Page 12Linked to original sources
PubMed1992

Epidermal growth factor receptor and transforming growth factor alpha expression in human ovarian carcinomas.

The varying tumorbiological behaviour of ovarian carcinomas probably influences operability, response to chemotherapy, being one of the most relevant prognostic factors. Because it is believed that an activation of the epidermal growth factor/transforming growth factor alpha (EGF/TGF alpha) signal pathway could be involved, we analysed the expression of epidermal growth factor receptor (EGFR) and TGF alpha with molecular-chemical, biochemical and immunohistochemical methods in 42 ovarian carcinomas, 4 ovarian metastasis, 2 other malignant ovarian tumours, and in 25 nonmalignant tissues (ovary, myometrium). No major rearrangements or amplification of the EGFR or TGF alpha genes were found. In non-malignant tissues no strong EGFR or TGF alpha signals were detected. TGF alpha is mainly produced by the tumour cells as shown by immunohistochemistry. Four different high molecular weight forms (20-48 kD) were detected in malignant tissues by western blot analysis.

Blotting, Northern↗
PubMed1992

High-efficiency gene transfer mediated by adenovirus coupled to DNA-polylysine complexes.

Employment of recombinant viruses as gene transfer vectors is limited by constraints on the size and functional design of the genetic material to be transferred as well as potential safety hazards deriving from obligatory co-transfer of viral genetic elements. As an alternative strategy that capitalizes on the efficient cellular entry mechanisms of viruses, we have derived adenovirus-polylysine-DNA complexes whereby foreign DNA is transferred bound to the exterior of the virion. This linkage was accomplished utilizing an antibody bridge in which a monoclonal antibody was rendered competent to carry DNA by the attachment of a polylysine residue. Attachment of the antibody-polylysine to the virus was by virtue of the antibody's specificity for the virion. The resulting vector system mediates high-efficiency gene transfer to target cells in vitro. In addition, this vector design allows greatly enhanced flexibility in terms of the size and design of heterologous sequences that can be transferred. Since this strategy selectively exploits viral entry functions, which are independent of viral gene expression, the potential exists to derive vectors that avoid the hazards deriving from transfer of parent virus genome.

Adenoviridae↗
PubMed1992

Pretransplant and posttransplant antibodies in human corneal transplantation.

The purpose of this study was to measure the association between antibody formation and endothelial corneal allograft reactions in 533 consecutive corneal graft recipients. The median follow-up time of these recipients was 732 days. Pretransplant panel-reactive antibodies were not found to be associated with endothelial corneal allograft reactions. Out of 533 recipients, 239 developed posttransplant antibodies during the course of this study. The formation of posttransplant antibodies was frequent in recipients with pretransplant antibodies and in HLA-A,-B-incompatible recipients. Posttransplant antibodies most often appeared within the first six months after transplantation whereas endothelial allograft reactions most often occurred later. Out of 65 recipients who developed PPRA and underwent an allograft reaction, 53 had a PPRA peak prior to, or at about the time of, the allograft reaction. Corneal allograft reaction events diagnosed during the second and third year after surgery were correlated with PPRA formation during the first year after grafting. The 36-month reaction-free survival rate of transplants was estimated at 72% in recipients with PPRA compared with 86% in recipients without PPRA (log rank P value = 0.002). Furthermore, posttransplant antibody formation altered the outcome of corneal allografts in both HLA-A and -B-compatible and -incompatible recipients. These findings suggest that posttransplant antibody development represents a high risk of endothelial corneal allograft reactions.

Antibodies↗
PubMed1992

Effect of bronchial smooth muscle contraction on lung compliance.

Lung compliance is generally considered to represent a blend of surface and tissue forces, and changes in compliance in vivo are commonly used to indicate changes in surface forces. There are, however, theoretical arguments that would allow contraction of airway smooth muscle to affect substantially the elasticity of the lung. In the present study we evaluated the role of conducting airway contraction on lung compliance in vivo by infusing methacholine (MCh) at a constant rate into the bronchial circulation. With a steady-state MCh infusion of 2.4 micrograms/min into the bronchial perfusate (perfusate concentration = 0.7 microM), there was an approximate doubling of lung resistance and a 50% fall in dynamic compliance. There were also significant decreases in chord compliance measured from the quasi-static pressure-volume curves and in total lung capacity and residual volume. When the same infusion rate was administered into the pulmonary artery, no changes in lung mechanics were observed. These results indicate that the conducting airways may have a major role in regulating lung elasticity. This linkage between airway contraction and lung compliance may account for the common observation that pharmacological challenges given to the lung usually result in similar changes in lung compliance and airway conductance. Our results also suggest the possibility that the lung tissue resistance, which dominates the measurement of lung resistance in many species, might in fact reflect the physical properties of conducting airways.

Airway Resistance↗
PubMed1992

On the purported discovery of the bronchial circulation by Leonardo da Vinci.

Among modern physiologists and anatomists, there has been a nearly universal acceptance that Leonardo da Vinci was the first to identify the anatomy of the bronchial circulation. However, because of certain ambiguities in both his anatomic drawing that was supposed to have shown this circulation and the accompanying descriptive text, we questioned whether he really could have been the first to discover this small but important vasculature. To address this question, we set out to repeat Leonardo's dissections in the ox. We reasoned that perhaps the normally tiny bronchial vessels would be considerably more noticeable in this very large species. Our dissections, however, failed to provide any evidence that Leonardo's drawing was that of the bronchial circulation. Furthermore we observed a set of distinct small pulmonary veins to the left upper and right middle lobes that Leonardo, given his lack of understanding of the function of the lung and its circulation, could have easily mistaken for a separate circulation. We thus conclude that Leonardo da Vinci did not describe the anatomy of the bronchial circulation. We believe that the first person to clearly and unequivocally describe the anatomy of this circulation was the Dutch Professor of Anatomy and Botany, Frederich Ruysch.

Anatomy, Artistic↗
PubMed1992

Gene transfer to respiratory epithelial cells via the receptor-mediated endocytosis pathway.

Gene-based therapies for a variety of inherited and acquired pulmonary diseases will require the development of vectors capable of safe and efficient transfer of DNA to the respiratory epithelium. The present study examined the feasibility of delivering DNA to respiratory epithelial cells by the receptor-mediated endocytosis pathway. This strategy employs molecular conjugates consisting of a cognate moiety, in this case human transferrin, covalently linked to a DNA-binding moiety, such as a cationic polyamine. Complexes were formed between transferrin-polylysine conjugates (hTfpL) and plasmid DNA carrying the firefly luciferase reporter gene (pRSVL). The conjugate-DNA complexes were added directly to cells in tissue culture and incubated for 24 h, after which cell lysates were analyzed for luciferase enzyme activity by luminometry. An immortalized human respiratory epithelial cell line (HBE1) treated with the transferrin-polylysine-DNA complexes exhibited luciferase enzyme activity significantly augmented over background levels. This respiratory epithelial cell line exhibited greater susceptibility to gene transfer by the transferrin-polylysine conjugates than did non-respiratory epithelial cell lines known to possess high levels of transferrin receptors. Effective gene transfer was shown to require both the DNA-binding moiety and cognate moiety for the cell surface receptor. Specific internalization of the conjugates by the transferrin pathway was verified by competition for the transferrin receptor. In addition, treatment with agents that either increased transferrin receptor number or decreased lysosomal degradation markedly augmented gene expression mediated by the conjugates. Thus, respiratory epithelial cells possess receptors for transferrin that can be exploited to accomplish gene transfer by the receptor-mediated endocytosis pathway.

Animals↗
PubMed1991

A simple procedure for the preparation of protected 2'-O-methyl or 2'-O-ethyl ribonucleoside-3'-O-phosphoramidites.

Protected 2'-O-methyl and 2'-O-ethyl ribonucleoside-3'-O-phosphoramidites were prepared via alkylation of the ribonucleosides at an early stage in the synthesis. Utilizing a strategy of minimal protection, the alkylation was performed with unprotected cytidine and adenosine, or with O6-protected guanosine and N3,5'-O-protected uridine using methyl or ethyl iodide and sodium hydride. In subsequent steps, the introduction of standard protective groups for oligonucleotide synthesis and the concomitant separation from 3'-O-alkylated isomers was accomplished. A modification of the phosphitylation procedure permitted facile isolation of the desired phosphoramidites which show high coupling efficiencies in oligomer assembly.

Ethane↗
PubMed1991

Adenovirus enhancement of transferrin-polylysine-mediated gene delivery.

Gene transfer may be accomplished by the receptor-mediated endocytosis pathway using transferrin-polylysine conjugates. For some target cells, however, gene transfer by this vector is extremely limited, despite the presence of the appropriate surface receptors, a phenomenon attributed to lysosomal degradation of endosome-internalized conjugate-DNA complexes. To enhance DNA escape from the cell vesicle system and thus augment gene transfer by this route, we have used the capacity of adenoviruses to disrupt endosomes as part of their entry mechanism. Adenoviral infection augmented levels of gene transfer by transferrin-polylysine conjugates in a dose-dependent manner: levels of gene transfer of greater than 2000-fold above baseline were achieved. Use of the adenovirus in this context allowed enhanced levels of gene transfer in a variety of target cells, including cell lines otherwise refractory to gene transfer by transferrin-polylysine conjugates. This augmentation was based on adenoviral-mediated vesicle disruption, a process independent of viral gene expression. Thus, the development of specific mechanisms to effect release from the endosome in combination with gene transfer by the receptor-mediated endocytosis pathway will increase the utility of this delivery system by allowing high levels of gene expression in target cells.

Adenoviridae↗
PubMed1991

2'-O-methyl, 2'-O-ethyl oligoribonucleotides and phosphorothioate oligodeoxyribonucleotides as inhibitors of the in vitro U7 snRNP-dependent mRNA processing event.

We describe the synthesis of 2'-O-methyl, 2'-O-ethyl oligoribonucleotides and phosphorothioate oligodeoxyribonucleotides and demonstrate their utility as inhibitors of the in vitro U7 snRNP-dependent mRNA processing event. These 2'-O-modified compounds were designed to possess the binding affinity of an RNA molecule towards a complementary RNA target with an enhanced stability against nucleases. The 2'-O-methyl and 2'-O-ethyl antisense compounds function as potent inhibitors of the reaction at 1-10 nM, approximately 5-fold more effective than a natural antisense RNA molecule and requiring an approximate 5-fold excess over the target RNA for 80% inhibition of the processing reaction.

Base Sequence↗
PubMed1991

Transferrin-polycation-DNA complexes: the effect of polycations on the structure of the complex and DNA delivery to cells.

We have previously described a gene delivery system based upon the receptor-mediated endocytosis of DNA complexed with transferrin-polycation conjugates. This delivery system has been found to be very effective for both the internalization and the expression of genetic material in cells that have many transferrin receptors. Upon scrutinization of the parameters involved in this method, which we have termed transferrinfection, we note two important features of the process: the polycation in polycation-transferrin conjugates, as expected, serves to attach the transferrin moiety to the DNA and, in addition, the polycation functions to condense the DNA into a doughnut structure. Electron microscopic analysis of a range of poorly active to highly active transferrinfection samples reveals a strong correlation between DNA condensation and cellular DNA uptake. Furthermore, we demonstrate that the transfection activity of the DNA complex can be increased by addition of free polycation as long as a sufficient quantity of polycation-transferrin conjugates remains in the complex to ensure its binding to the cellular receptor.

Amino Acid Sequence↗
PubMed1991

Community-level comparisons between the grocery store environment and individual dietary practices.

BACKGROUND: This article examines the relationship at the community level between individual dietary practice and the grocery store environment. METHODS: Individual dietary practice was measured in 12 communities using a telephone survey to obtain self-reported diet. A protocol was developed to measure two aspects of the grocery store environment in these same 12 communities: the relative availability of healthful (low-fat and high-fiber) products, and the amount of health-education information provided. Comparisons were made between individual and store-level measures at two levels of geographic aggregation: community (typically a county) and zip code within community (n = 34). RESULTS: We found positive and statistically significant correlations at both the community and the zip code level between the availability of healthful products in stores and the reported healthfulness of individual diets. Positive correlations were also found between measures of the amount of health-education material provided by stores and the healthfulness of individual diets, but these correlations did not reach statistical significance. CONCLUSIONS: The results provide support for including measures of the grocery store environment as part of a community-level assessment of dietary behavior.

Adult↗
PubMed1991

[Ultrasonic diagnosis of tumors of the cecum and ascending colon].

The results of preoperative ultrasound investigations were compared with the intraoperative findings in 42 patients (27 women, 15 men) operated on because of tumours of the cecum or colon ascendens. In 34 of 42 patients (i.e. 81%) the tumour could be correctly diagnosed by ultrasound. In 3 cases the investigator was not sure about imaging the tumour. Only in 5 cases (i.e. 12%) the tumour was not identified by ultrasound scanning. 4 out of these 5 patients had attended the hospital to be operated on because of a carcinoma of the rectum and the second carcinoma of the large bowel was found by chance intraoperatively. In 16 patients in whom the diagnosis of a large bowel carcinoma had not been established before, the tumour could be primarily diagnosed by ultrasound.

Adult↗
PubMed1991

High-resolution PET studies in Alzheimer's disease.

Forty-seven patients with probable dementia of the Alzheimer type (DAT) and 30 healthy age-matched controls were scanned using [18F]-2-fluoro-2-deoxy-D-glucose on a Scanditronix PC 1024-7B tomograph (inplane resolution = 6 mm, axial resolution = 10 mm). Patients and controls were scanned in the resting state with their eyes patched and ears occluded. The regional cerebral metabolic rates for glucose (rCMRglc) in most major neocortical and subcortical gray matter regions, and certain metabolic ratios (rCMRglc/ calcarine rCMRglc), quantitatively discriminated even the mildly demented patients from healthy controls. The association neocortices showed metabolic abnormalities that were more severe than those in the sensorimotor and calcarine regions. All demented groups showed significant neuropsychological disturbances when compared to healthy controls. These data demonstrated widespread metabolic disturbances, particularly in the association areas, relatively early in Alzheimer's disease, and more profound involvement with disease progression.

Alzheimer Disease↗
PubMed1990

Effect of gender on glucose utilization rates in healthy humans: a positron emission tomography study.

Positron emission tomography (PET) was used with 18fluorodeoxyglucose to see if gender differences in resting cerebral glucose utilization could be detected. Thirty-two healthy subjects (15 women and 17 men; age range: 21-38 yr) were examined using a high-resolution PET scanner to determine the regional cerebral metabolic rate for glucose (CMRglc) in 65 gray matter regions of interest. Whole brain CMRglc did not differ significantly between the two genders, nor did any of the regional CMRglc values. Only 1 of 65 ratios of regional-to-whole brain CMRglc differed significantly between men and women, which is consistent with chance. These results indicate that there are no differences in resting regional cerebral glucose utilization between young men and women.

Adult↗
PubMed1990

Long-term culture and characterization of human limbal microvascular endothelial cells.

Human limbal explants obtained from 44 eyebank donors were cultured in medium 199 supplemented with 20% fetal bovine serum, vascular endothelial cell growth supplement and heparin. Cells grew abundantly out of the explants. They initially formed a 'cobblestone' patterned monolayer but later exhibited an elongated morphology with growth in parallel bundles. These cells could be passaged at least nine times and were identified throughout the consecutive passages as microvascular endothelial cells by the expression of factor VIII-related antigen, laminin and of the H determinant of ABO blood groups. As expected from vascular endothelial cells, flow cytometric analysis demonstrated a strong expression of class I histocompatibility antigens and a weaker expression of class II antigens. Class II antigen expression was enhanced by culturing the cells in the presence of immune interferon. These cells produced immunoreactive interleukin-1, mainly of the alpha type, under endotoxin stimulation. Limbal microvascular cells could be useful to study corneal angiogenesis. Furthermore, long-term culture of limbal cadaveric tissue can potentially be used to characterize donor-specific immunologic responses in corneal graft recipients.

ABO Blood-Group System↗
PubMed1990

Distressed high utilizers of medical care. DSM-III-R diagnoses and treatment needs.

Among a sample of 767 high utilizers of health care, 51% were identified as distressed by an elevated score on the SCL anxiety and depression scales, the SCL somatization scale, or by their primary-care physician. These distressed high utilizers were found to have a high prevalence of chronic medical problems and significant limitation of activities caused by illness. In the prior year, they made an average of 15 medical visits and 15 telephone calls to the clinic. The Diagnostic Interview Schedule was completed on 119 distressed high utilizers randomly assigned to an intervention group in a controlled trial of psychiatric consultation. The following DSM-III-R disorders were most common: major depression 23.5%, dysthymic disorder 16.8%, generalized anxiety disorder 21.8%, and somatization disorder 20.2%. Two thirds had a lifetime history of major depression. The examination resulted in an improved diagnostic assessment for 40% of intervention patients and a revised treatment plan for 67%.

Adolescent↗