PubMed Health⌕ Search

Biomedical subjects

F Steinberg

Publications and source records attributed to F Steinberg.

At least 37 records · Page 2Linked to original sources
PubMed1992

Vascular patterns of tumors: scanning and transmission electron microscopic studies on human xenografts.

The tumor vascular system plays a significant role both in tumor growth and metastasis as well as in therapy. However, there are comparatively few papers dealing with the morphology and architecture of tumor vascularity. This is inconceivable insofar as structural and architectural parameters determine tumor blood flow. Therefore, the vascular system of eight human tumor lines transplanted onto 121 thymus-aplastic nude mice was studied with light, scanning and transmission electron microscopy as well as microvascular corrosion casting. All tumors show a connective tissue-like capsule with a dense plexus of vessels forming a "vascular envelope". Particularly in early stages, these vessels follow a tortuous course with glomeruloidal arrangement and numerous indications of angiogenic activity. In the tumor centre regular arteries and veins are never to be seen. Instead, all vessels show a capillary wall construction with variations in height and electron densities of the endothelial cells. Changes in vessel diameter, lack of vascular hierarchy, blind ends as well as irregular sinusoidal systems originating from and draining to veins are common features. The vascular densities vary considerably within single tumors. Based on the vascular architecture and wall construction, necroses may occur even in areas with intervascular distances of only 15 microns. No significant differences in vascular architecture of the various cell lines could be observed.

Animals↗
PubMed1991

Radiation-induced changes in lung tissue and development of fibrosis determined by quantitative morphometric methods.

This study presents results of morphometric investigations of mouse lungs after single irradiation. An automatic image analyser was used to monitor pathological changes in morphological structure, especially the size and distribution of collagen fibres, the thickness of the septa and the diameters of alveoli in the lung. Radiation-induced changes in the area of alveoli and septa as well as collagen content were seen 11 weeks after irradiation. A dose-dependent increase in tissue and decrease in alveolar surface as well as a quantifiable increase in radiation oedema were seen. The septa were thickened and the total collagen content increased in a dose-dependent manner. The morphometric methods used here are suitable for determining changes in lung structure, particularly those in collagen content in the early phase of a pathological response after thorax or total body irradiation for conditioning in bone marrow transplantation.

Animals↗
PubMed1990

The vascular architecture of human xenotransplanted tumors: histological, morphometrical, and ultrastructural studies.

This study was designed to examine the vascular system of human xenotransplanted tumors on nude mice with different complementary morphometrical and morphological methods. The vascular system shows a chaotic arrangement. There is an extreme heterogeneity in the vascular distribution and density. Large avascular regions could be identified in several non-necrotic tumors. There was no clear difference in the vascular density between the center and the periphery of the tumors, nor was there any zonal correlation for the distribution of the necrosis. With three-dimensional corrosion casts it could be demonstrated that clusters of vessels were directly beneath areas almost free of vessels. In the center, vessels often form a sinusoidal system with numerous blind ends without clearly discernible endothelial cells. Numerous irregular tumor-cell-lined sinusoids are visible next to endothelial-lined vessels with transmission electron microscopy. With scanning electron microscopy it could be demonstrated that large-calibre endotheliazed vessels were found in the direct vicinity or in the center of non-viable zones. Even large-calibre vessels have a capillary wall structure. Sometimes, a basement membrane cannot be observed at all or only incompletely. There are numerous indications of vascular discontinuities and leaks with a widespread intercellular occurrence of blood cells.

Animals↗
PubMed1990

The vasculature of xenotransplanted human melanomas and sarcomas. 3. Morphometric studies.

Morphometric measurements of xenotransplanted tumors allowed the evaluation of vascular distribution and density. The correlation between these two parameters and the amount of necrosis could be determined. A wide range of vascular densities between different tumors was measured. This extreme heterogeneity of vascular distribution and density was seen in the center as well as in the periphery of single tumors. Large avascular regions were identified in several tumors that were not necrotic. The distribution of the necrosis showed no zonal correlation, either. No correlation was observed between the density of vessels and the amount of necrosis.

Animals↗
PubMed1989

Stomal varices: percutaneous transhepatic embolization.

Peristomal varices occasionally form in patients with chronic liver disease who have surgically created intestinal anastomoses and stomas. Hemorrhage from these varices carries an estimated mortality of 3%-4% per episode, as opposed to the 30%-40% mortality associated with gastroesophageal variceal bleeding. The cases of four patients who underwent transhepatic mesenteric vein catheterization with embolization of stomal varices for recurrent, intractable bleeding are presented. In three of the four patients there was no additional hemorrhage for at least 5 months. One patient was lost to follow-up. There were no complications. Since stomal variceal hemorrhage has a low mortality, transhepatic embolization is presented as a means of hemorrhage control when sclerotherapy fails and when shunt surgery presents an unacceptably high rate of morbidity and mortality relative to the underlying disease.

Aged↗
PubMed1989

The vasculature of xenotransplanted human melanomas and sarcomas on nude mice. I. Vascular corrosion casting studies.

The vascular system of xenotransplanted human melanomas and sarcomas on nude mice was studied by means of microorrosion casting. In summary, the vascular system of xenotransplants can be described in termes of a simply structured system, lacking not only a hierarchy with respect to wall formation but also to vascular distribution. Thus, the vasculature clearly differs from that in normal tissues.

Animals↗
PubMed1989

The vasculature of xenotransplanted human melanomas and sarcomas on nude mice. II. Scanning and transmission electron microscopic studies.

The tumor-inherent vasculature plays a major role with respect to tumor sensitivity to ionizing radiation. Ultrastructural studies of the tumor vasculature are necessary in order to obtain more detailed information on the architecture and structure and on the sites affected by tumor therapy. The vasculature of xenotransplanted human tumors on nude mice was investigated in this study by means of scanning and transmission electron microscopy. Structurally complete, real arteries or veins are neither to be seen in the periphery nor in the center. Large-caliber vessels basically have a capillary wall structure. The endothelial cells show a very alternating height and electron density. Frequently, different cell types and tumor cells themselves are apparently involved in the formation of the vessel wall. The endothelium is characterized by very simple, immature cell contacts. In some tumors, the amount of vessels without or with incomplete endothelium seems to be higher than the number of structurally real capillaries. This has consequences as well for radiotherapy as for hyperthermia and chemotherapy.

Animals↗
PubMed1989

The vascular system of xenotransplanted tumors--scanning electron and light microscopic studies.

A widely used model for investigating basic tumor characteristics and different treatment modalities preclinically is the immune-deficient, athymic nude mouse. This model offers many morphological parallelisms to the clinical situation. The aim of this study is to demonstrate the vascularization pattern of xenotransplanted human melanomas and sarcomas using different methods. Xenotransplanted tumors of 62 congenital thymus-aplastic nude mice were examined ultrastructurally and topographically after corrosion cast and tissue preparation. Quantitative measurements of tumors injected with India ink were carried out to obtain comparable information on the vascular densities in the tumors. Quantitative measurements showed that there is no zonal, topographic arrangement of the vascular densities. Comparisons of the vascular densities in the centers of tumors with the densities in the periphery showed an extreme heterogeneity in tumor vessel distribution, which does not generally support the idea of a better vascularisation in the tumor periphery. Neither in the periphery nor in the center of the tumor regular vessels are to be seen consisting of intimal, medial and adventitial layers. Even the largest peripheral vessels, which often take a tortuous course, consist mainly of an endothelial layer and some perivascular connective tissue only. Areas with high vascular densities could be seen just beneath areas almost free of vessels. Besides endothelial-lined vessels numerous irregular, tumor cell-lined sinusoids are visible both in sarcomas and melanomas. The morphology of the vessels found scanning electron microscopically is generally in agreement with many features described transmission electron microscopically.

Animals↗
PubMed1984

ADP-ribosylation of transducin by pertussis toxin blocks the light-stimulated hydrolysis of GTP and cGMP in retinal photoreceptors.

Cholera toxin and pertussis toxin catalyze ADP-ribosylation of the alpha-subunits of the GTP-binding stimulatory (Ns) and inhibitory (Ni) coupling components, respectively, of adenylate cyclase. Cholera toxin also catalyzes the ADP-ribosylation of transducin, the GTP-binding signal-coupling protein of retinal rod outer segments, and thereby reduces its light-stimulated GTPase activity. We show here that pertussis toxin also ADP-ribosylates transducin. Illumination markedly inhibits the ADP-ribosylation of transducin by pertussis toxin. ADP-ribosylation by this toxin in the dark is also lessened by prior incubation with hydrolysis-resistant GTP analogs. These inhibitory effects indicate that the GDP complex of transducin is the preferred form for ADP-ribosylation by pertussis toxin. Transducin modified by this toxin has a lower affinity for photoexcited rhodopsin than does unmodified transducin. ADP-ribosylation inhibits the light-stimulated GTPase activity of rod outer segments and blocks the signal-coupling activity of transducin in photoactivation of the phosphodiesterase. These and previous results show that cholera and pertussis toxins preferentially ADP-ribosylate the active (GTP-binding) and inactive (GDP-binding) conformations, respectively, of transducin. Correspondingly, ADP-ribosylation by these toxins inhibits GTPase activity by stabilizing transducin in the preferred active (GTP-binding) or inactive (GDP-binding) conformation. The actions of pertussis toxin on retinal rod outer segments provide further evidence for a high degree of homology between retinal transducin and the N proteins of the adenylate cyclase system.

Adenylate Cyclase Toxin↗
PubMed1983

Identification by direct photoaffinity labeling of an altered phosphodiesterase in a mutant S49 lymphoma cell.

Extracts of a mutant S49 lymphoma cell line, termed K30a, hydrolyze cAMP and cGMP at rates much faster than do wild type S49 extracts. This elevated phosphodiesterase activity, called K-PDE, elutes as a single peak of activity on DEAE-cellulose columns (Brothers, V. M., Walker, N., and Bourne, H. R. (1982) J. Biol. Chem. 257, 9349-9355). Direct photoaffinity labeling of K30a extracts with [32P]cGMP results in radiolabeling of a unique polypeptide, not observed in wild type extracts, which migrates in sodium dodecyl sulfate polyacrylamide gels with an Mr = 106,000. The 106-kDa band was identified as the catalytic K-PDE polypeptide based on the following observations: competitive inhibitors and substrates of K-PDE inhibit photolabeling of the 106-kDa band, indicating that [32P] cGMP photolabels the enzyme at its catalytic site; on DEAE-cellulose chromatography the polypeptide that is susceptible to photolabeling co-elutes with K-PDE activity; the 106-kDa band is detectable in extracts of WT X K30a hybrids (where WT denotes wild type) in amounts proportional to the K-PDE activity in the hybrids, but is undetectable in wild type. The hybrid phenotype strongly suggests that the K30a phenotype is not due to mutations that affect either a diffusible regulator of transcription or an enzyme that modifies K-PDE. Although wild type cells contain a minor cGMP phosphodiesterase activity distinct from the major cAMP phosphodiesterase, the wild type cGMP phosphodiesterase is not susceptible to radiolabeling with [32P]cGMP; this rules out the possibility that the K30a phenotype is caused by overexpression of a wild type phosphodiesterase. We conclude that the K30a mutation produced expression of a new species of phosphodiesterase molecule that is not detectably expressed in the parental S49 wild type cell line.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

A convenient method for measuring receptor-cyclase coupling activity in whole blood: application to Duchenne muscular dystrophy.

Activity of the guanine nucleotide-binding regulatory (N protein) component of adenylate cyclase can be measured in extracts of whole blood, using a modification of an assay previously applied to erythrocyte membranes. N protein activities in the blood of three patients with Duchenne muscular dystrophy and eight heterozygous carriers of the disease did not differ significantly from activities measured in blood of seven normal subjects. In contrast, the modified assay showed a 50% deficiency of N protein activity in blood of four patients with pseudohypoparathyroidism, type I, in whom erythrocyte studies had previously demonstrated a comparable degree of N deficiency.

Adenylyl Cyclases↗