Angiogenic factor in ocular fluid.
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Biomedical subjects
Publications and source records attributed to J B Weiss.
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Foetal heart rate and tocodynamic monitoring of the uterus was performed in five pregnant patients undergoing urgent or emergency surgery unrelated to their pregnancy. All received general anaesthesia with halothane or enflurane and nitrous oxide. The loss of beat-to-beat variation of the foetal heart rate was observed in all patients under general anaesthesia, and is probably normal for the anaesthetized foetus. Since continuous intraoperative monitoring of foetal heart rate in pregnant patients is technically feasible during peripheral surgery and during many intra-abdominal procedures, attempts should be made to monitor foetal heart rate in all anaesthetized parturients to assure that the anaesthetic is not causing foetal insult. Postoperative monitoring of uterine tone is useful in the diagnosis and treatment of postoperative premature labor.
A major surface antigen of Schistosoma mansoni has been identified and characterized as a glycoprotein of 66,000 molecular weight (Mr) and isoelectric point of 6.2-6.1 (SM66-GP) by use of a monoclonal antibody. The antigen was expressed by schistosome eggs, cercariae, larvae, and adults, and was recognized by sera of schistosome infected hosts. Direct immunofluorescence microscopy showed the antigen was distributed in a uniform pattern on the entire worm surface. Indirect immunofluorescence microscopy revealed that it was present in the parenchymal tissue of immature and mature Fasciola hepatica, in the gut of the mature fluke, and in embryonated fasciola eggs. The cross-reactive F. hepatica epitope recognized was expressed on a polypeptide of Mr 220,000.
The chemical and antigenic composition of a major group of concanavalin A-binding glycoprotein antigens of Schistosoma mansoni eggs was examined by the use of monoclonal antibodies. The individual glycoproteins of this group each displayed a very wide range of apparent m.w. and had isoelectric points of less than 5 when analyzed by two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. These glycoproteins could be chemically labeled with 125Iodine by two different methods and biosynthetically labeled with 35S-methionine during in vitro synthesis by isolated eggs. By using five monoclonal antibodies, the individual egg glycoproteins were shown to share several antigenic determinants when analyzed by radioimmunoprecipitation and solid-phase binding assays. These epitopes were present in a high level, and the degree of expression appeared to be developmentally regulated. In addition, Schistosoma haematobium and Schistosoma japonicum eggs contained antigenically related glycoprotein antigens. Preliminary evidence suggests that the epitopes involve carbohydrate moieties.
Two methods were used to extract angiogenic activity from bovine retina. Both methods initially gave rise to nondialyzable (greater than 10,000 Mr) fractions with angiogenic activity. However, after anion exchange chromatography, 20% of the extracts from one of the two methods (method 2) contained a small molecule with angiogenic activity (Mr 300-600). Alcohol treatment of high molecular mass fractions from both methods also released a low molecular mass angiogenic factor (Mr 300-600). No angiogenic activity was left in the nondialyzable residue. The high molecular mass angiogenic fraction obtained by method 1 after DEAE-cellulose chromatography contained a protein immunologically and electrophoretically identical to bovine serum albumin. The low molecular mass retinal angiogenic factor was able to stimulate microvessel endothelial cell proliferation as well as being positive in the chick chorioallantoic membrane test. The presence of a protein carrier system for a small angiogenesis factor is proposed. This would explain discrepancies in the apparent molecular mass of retinal angiogenic factors described previously.
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The collagens of bovine vitreous-humour and nasal-septum cartilage have been extracted, fractionated and compared. Both tissues show the same heterogeneity of collagen types, consisting of type II, 1 alpha, 2 alpha, 3 alpha and C-PS collagens. The type II collagen of the vitreous humour was significantly more hydroxylated both in the lysine and proline residues than was that of cartilage. C-PS1 collagen, together with higher-Mr forms were present in the vitreous humour, but the higher-Mr forms were not seen in cartilage. Both C-PS1 and C-PS2 were present in vitreous humour and cartilage, but vitreous humour contained three times more of these collagens than did cartilage. Despite the difference in amount, the molar ratio C-PS1/C-PS2 was approx. 1 in both tissues, suggesting that they are components of a larger molecule. The 1 alpha, 2 alpha, 3 alpha collagens were present in the same concentration in both tissues. These three chains co-precipitated on dialysis against phosphate-buffered saline, pH 7.2, in a manner analogous to type V collagen.
Human umbilical vein endothelial cells grew equally well in sera from scleroderma patients and in sera from rheumatic controls. Using two independent methods of assessing cell growth, no evidence of a previously described endothelial cell cytotoxic factor could be found in heat inactivated sera from 23 scleroderma patients. The system used was sensitive in detecting growth inhibition due to five batches of foetal calf serum and low concentrations of homocysteine and 2-mercaptoethanol.
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Protein antigens present in the hepatic lesions of mice infected with Schistosoma mansoni were identified by use of fluorochrome-conjugated monoclonal antibodies. All 26 monoclonal antibodies used in these experiments recognized antigenic determinants expressed by both cercariae and adult worms; 23 of these epitopes were also expressed by S. mansoni eggs. These results suggest considerable antigenic conservation during schistosome development. Two antibodies recognizing determinants absent from the egg nevertheless bound to schistosome antigens in hepatic granulomata; this result suggests that circulating worm antigens were also cleared in these lesions. Fifteen antigens were detected in perivascular spaces 5 weeks after infection, before the appearance of eggs in the liver.
A low-Mr freely dialysable endothelial cell-stimulating angiogenesis factor (ESAF) from conditioned medium of a mouse lymphoma cell line has previously been shown to activate latent skin fibroblast procollagenase. Activation comparable with the maximum that can be achieved with trypsin is obtained with chemically undetectable amounts of the factor. We now show that when even smaller amounts of ESAF are used heparin is able to potentiate its action in this system. The relationship between this activity and the mechanism of angiogenesis, which is itself potentiated by heparin, is discussed.
Vitreous from patients with proliferative diabetic retinopathy contains an angiogenic substance which stimulates the proliferation of blood vessels on the chick chorioallantoic membrane, whereas vitreous from non-diabetics who do not have a proliferative retinopathy does not.
Immunoglobulin allotype markers and HLA-A, HLA-B, and HLA-DR locus antigens were determined in 30 White patients with gluten-sensitive enteropathy and 30 controls matched for age, ethnic background, and geographic origin. All patients lacking HLA-B8 and HLA-DR3 had the IgG (Gm) immunoglobulin heavy-chain phenotype Gm (f;n;b). Thus, in addition to major histocompatibility locus genes, it appears that genes linked to the immunoglobulin heavy-chain allotype locus on chromosome 14 may influence susceptibility in gluten-sensitive enteropathy.
Avascular tumours have the ability to establish a blood supply for themselves by secreting a humoral factor which stimulates their host's endothelial cells to proliferate and to migrate towards the tumour source. The mechanism of action of such a humoral angiogenesis factor is more than that of an endothelial-cell growth factor since it requires an oriented migration of cells towards the tumour. We report here the activation of pure skin-fibroblast procollagenase by a low-molecular-weight angiogenesis factor capable of stimulating endothelial-cell growth in vitro. The activation was observed when either Type I or III collagen was used as substrate. It is suggested that at least one function of angiogenesis factor is to promote limited degradation of the connective tissue through which it passes causing channeling in the matrix along which stimulated endothelial cells may migrate.
Collagen was extracted with neutral salt solution and examined for the presence of type V collagen. A fraction which was insoluble in both 0.02 M Na2HPO4, pH 9.2 and phosphate-buffered saline (PBS) pH 7.2 at 4 degrees C contained both alpha 1(V)- and alpha 2(V)-chains demonstrated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, diethylaminoethyl cellulose ion exchange chromatography, amino acid analysis and segment long spacing (SLS) crystallites. SLS crystallites showed a globular N-terminal extension peptide attached to the type V collagen monomer. Ion exchange chromatography also demonstrated the presence of a third, minor component, which was identified as the alpha 3(V)-chain. In certain extractions, components corresponding to the partially processed procollagen chains of type V collagen were also observed.
Bone metabolism in 21 patients with rheumatoid disease was investigated by measurement of the 24-hour whole body retention (WBR) of 99Tcm methylene diphosphonate (MDP) in parallel with clinical, radiological, and biochemical measurements (urinary excretion of hydroxyproline) of disease activity. Corticosteroid-treated patients of those with other forms of metabolic bone disease were excluded from the study. WBR was increased in the rheumatoid patients as compared with 21 age- and sex-matched controls (p less than 0.05), and there was a significant correlation in the rheumatoid group between WBR and urinary excretion of hydroxyproline (p less than 0.01) and between urinary excretion of hydroxyproline and an articular index (p less than 0.05) and global index (p less than 0.01) of disease activity. The increased WBR of the rheumatoid patients was not explicable by factors such as immobilisation, and the results are interpreted as reflecting an overall increase in bone metabolism which may occur in rheumatoid arthritis as part of the disease process.
A low-molecular-weight freely dialysable angiogenesis factor has been isolated from 49 synovial fluids obtained from patients with various joint diseases. An analysis of disease type and incidence of freely dialysable angiogenesis activity showed that the osteoarthrotic group had a significantly higher incidence than all the other groups (p = 0.0332). Angiogenesis factor has also been detected in a bound form in the retentates of fluids which gave positive results for dialysable factor. The possibility that an imbalance between carrier-bound and free factor may have a causative role in disease is discussed.
Collagens type I, II, III, IV, and V and the minor cartilage collagens, 1 alpha 2 alpha 3 alpha, C-PS 1, and C-PS 2, were purified, antibodies raised, and then used in immunofluorescence studies on bovine nasal cartilage (BNC). Punctate localisation was seen with the type II antibody. However, pretreatment of sections with hyaluronidase to remove the proteoglycan resulted in diffuse staining over all the section with this antibody. Antibodies to 1 alpha 2 alpha 3 alpha, C-PS 1, and C-PS 2 collagens gave no staining on untreated BNC sections, but after treatment with hyaluronidase all 3 antibodies showed as a diffuse 'halo' round each chondrocyte lacuna. Anti-type I, anti-type III, and anti-type IV collagen antibodies did not stain untreated or enzyme treated BNC. Type V collagen antibodies gave a bright ring in the pericellular region of the lacunae of hyaluronidase-treated BNC. This was unexpected, as we could not detect type V collagen biochemically in the same cartilage. Anti-fibronectin antibodies stained areas distant from the chondrocytes, these areas being distinct from those stained by 1 alpha 2 alpha 3 alpha and C-PS antibodies, suggesting that fibronectin is not associated with these collagens in BNC. These results suggest that different collagen types may have different locations within the cartilage matrix, that proteoglycans may inhibit antibody association with collagen, and that fibronectin is normally not associated with all types of collagen.