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Biomedical subjects

K L Kaplan

Publications and source records attributed to K L Kaplan.

At least 19 recordsLinked to original sources
PubMed1995

Reduced thrombogenicity of type VI collagen as compared to type I collagen.

Type VI collagen has been recently identified as a major constituent of vascular subendothelium where it serves as a binding site for von Willebrand factor. The present study compares the functional characteristics of type VI collagen with those of type I collagen with respect to platelet aggregating and secretory activities. The differences between the two collagens in platelet aggregation and serotonin and beta-thromboglobulin release were found to be highly significant (p < 0.001, p < 0.0007, p < 0.005 respectively). Our results indicate that under in vitro conditions, type VI collagen stimulates a significantly lesser platelet activation and aggregation response than collagen I, suggesting that type VI collagen may play a role in vivo to limit the platelet thrombotic response following injury to the vascular subendothelium.

Collagen↗
PubMed1991

Anticoagulant effects of nonionic versus ionic contrast media in angiography syringes.

To determine whether nonionic contrast media present a clotting hazard when plastic or glass injection syringes are contaminated with aspirated blood, we evaluated two nonionic (iohexol and iopamidol) and two ionic (ioxaglate and diatrizoate) contrast agents. We used a blood:contrast media ratio of 2 mL:5 mL and ten normal donors, each studied at 10, 20, 30, and 60 minutes, a parallel study of clotting and fibrinopeptide A (FPA) generation in plastic tubes, and life table analysis to estimate more accurately donor-based early clotting probabilities. While ionic contrast media are stronger anticoagulants, both nonionic and ionic media retard clotting in plastic tubes, and clotting in plastic and glass angiography syringes in comparison to saline controls. A clotting probability of 1% for nonionic agents in plastic syringes was not reached until a time (mean +/- SD) of 21.5 +/- 3.2 minutes. This contrasts with a time of 8.7 +/- 2.5 minutes for saline control. With plastic syringes, no clotting at all was observed at 10 and 20 minutes with either class of agents. Neither class of agents hastened the generation of FPA. We found no evidence, therefore, that nonionic agents either cause clots or are procoagulant.

Angiography↗
PubMed1991

Inducible release of an endothelial cell-specific protein.

The authors investigated the release of an endothelial cell-specific protein (E92) by cultured porcine aortic endothelial cell cultures. Under normal culture conditions, endothelial cells released little or no E92 into the culture supernatant. Treatment with thrombin (0.01 to 10 units/ml), endotoxin (0.01 to 10 micrograms/ml), or interleukin-1 (0.01 to 3.0 units/ml), however, caused significant, dose-dependent increases in E92 detectable in the culture supernatants. Time-course experiments showed that maximum release of E92 into cellular supernatants occurred 24 hours after stimulation with all mediators. Parallel experiments used 51Cr-loaded endothelial cells as a measure of lethal cellular injury. None of the mediators caused significant injury at the doses observed to induce release of E92. These results suggest that the release of E92 into the supernatants of cultured endothelial cells is an inducible event. The data also support the hypothesis that detection of E92 antigen in sera from patients with rheumatic disease represents a marker of in vivo vascular endothelial cell activity.

Animals↗
PubMed1991

Detection of circulating endothelial antigen.

In order to determine whether endothelial cell antigens are detectable in serum from patients with rheumatic disease characterized by vascular involvement, we developed an ELISA using a monoclonal antibody directed against a 92,000 molecular weight endothelial cell specific antigen designated E92. Sera were assayed from 191 patients and 34 healthy controls. E92 was undetectable or present in very low concentrations in healthy controls and was elevated in most patients with an active rheumatic disease. Our results indicate that circulating endothelial antigens are present in rheumatic vascular syndromes and may provide a measure of endothelial cell function.

Adolescent↗
PubMed1990

Fibrin and the vessel wall.

Fibrin is a major component of atherosclerotic plaques, and there may also be situations in which intravascular fibrin is formed in contact with the endothelium. The studies to be presented describe the distribution of fibrinogen/fibrin I, fibrin II, and fragments D and D-dimer in normal vessels and atherosclerotic plaques of increasing severity and also describe some functional effects of fibrin on normal endothelium. Immunohistochemical studies using three specific monoclonal antibodies with the avidin-biotin complex immunoperoxidase technique demonstrated that little fibrinogen/fibrin I or fibrin II and no D/D-dimer were detected in normal aortas. In early lesions and in fibrous plaques, fibrinogen/fibrin I and fibrin II were distributed in long threads and around vessel wall cells. D/D-dimer was not seen in early lesions. In advanced plaques all three molecular forms were detected in areas of loose connective tissue, in thrombi, and around cholesterol crystals. Thus increased fibrin formation and degradation may be associated with progression of atherosclerotic disease. Additionally, the presence of fibrin II around vessel wall cells suggests that these cells may be involved in the fbgn to fibrin transition within the vessel wall. The second aspect of the work to be presented concerns effects of fibrin on vascular endothelium. Fibrin formed on the surface of cultured human umbilical vein endothelial cells stimulated production of prostacyclin and tissue plasminogen activator by the cells in a time- and dose-dependent manner. Stimulation of prostacyclin was completely inhibited by indomethacin and partially inhibited by actinomycin D, cycloheximide, and trifluoperazine, while stimulation of t-PA synthesis was completely inhibited by actinomycin D and cycloheximide and partially inhibited by cytochalasin D, vinblastine, and trifluoperazine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Thrombosis in atherogenesis.

This review addresses the question of the involvement of fibrin in the development of atherosclerotic plaques. Numerous studies in the older literature demonstrated the presence of fibrinogen and/or fibrin in plaques, but the techniques that were available (mainly immunochemistry and immunohistochemistry with polyclonal antifibrinogen antibodies) did not clearly distinguish fibrinogen from fibrin or fibrinogen/fibrin degradation products. Some of these studies suggested that the fibrinogen-related protein within lesions resulted from incorporation of thrombi into lesions, while other studies suggested that fibrinogen itself entered the vessel wall. Newer studies by the authors and collaborators used specific antibodies for various fibrinopeptides to quantitate fibrinogen, fibrin I, fibrin II, and fragment X in thrombi and different histologic types of plaques. These studies showed that normal aortas contained fibrinogen and that fatty and fibrous plaques contained fibrinogen, fibrin I, and fibrin II, while complicated plaques contained fibrin II and fragment X, indicating a progression from fibrinogen to fibrin and fibrinogen/fibrin degradation products in parallel with increasing severity of the lesions. Later studies by the authors and collaborators used a sensitive immunohistochemical technique with monoclonal antibodies to demonstrate the distribution of fibrinogen-related antigens. Patterns suggesting incorporation of thrombi were seen, as were patterns suggesting formation of fibrin in association with arterial wall monocyte/macrophages and smooth muscle cells. The data from these various studies suggest the possibility that fibrin formation occurs within the arterial wall and contributes to plaque formation.

Antigens↗
PubMed1989

Immunohistochemical characterization of fibrin(ogen)-related antigens in human tissues using monoclonal antibodies.

A new approach to study the distribution of fibrin(ogen)-related antigens was investigated using three different monoclonal antibodies (MAbs) and the avidin-biotin complex immunoperoxidase technique. MAb I8C6 recognizes B beta 1-42 peptide and can react with either fibrinogen or fibrin I; MAb T2G1 recognizes B beta 15-42 peptide and detects fibrin II but does not cross-react with fibrinogen; MAb GC4 reacts with Fragments D/DD derived from plasmin degradation of fibrinogen or fibrin but not with intact fibrinogen. The method can be applied to frozen or Bouin's fixed paraffin-embedded tissues obtained at biopsy, surgery, and autopsy. The distribution of the three antigens observed with the three MAbs was compared with that obtained with a polyclonal antiserum to fibrinogen and with the more conventional histochemical stains used in pathology to demonstrate fibrin deposits in tissues (Lendrum and PTAH). The staining observed with the three monoclonals clearly detected three different populations of fibrin(ogen)-related antigen in the tissues examined. The staining with MAb T2G1 specifically detected fibrin II with greater sensitivity than did conventional stains. The results of this study suggest that this method allows the molecular form of fibrin(ogen)-related deposits in tissues to be determined and this information may help to elucidate the role of fibrin in various disease states, such as atherosclerosis and renal disease, and in tumor growth and metastasis.

Antibodies, Monoclonal↗
PubMed1987

Blood tests for the detection of thrombosis. Effects of blood flow and location of the sampling site.

Assays are available that allow the careful and wary investigator to use blood samples to derive useful information about hemostatic system activity. In practice the validity of the data will depend in very large part on the care which is taken in sample collection and processing. The particular system being studied profoundly influences the way in which the study should be performed. The details of the interacting issues are not yet resolved, and can only be dealt with as caveats. Finally and most importantly, these assays can not and should not be used to make the diagnosis of thrombosis. We believe that in general their use should be restricted to studies of pathophysiology. They are tools of exquisite sensitivity and specificity that allow us to probe the thrombotic process, and with care and imagination perhaps thrombogenesis itself.

Biocompatible Materials↗
PubMed1987

Immunochemical characterization of fibrinogen, fibrin I, and fibrin II in human thrombi and atherosclerotic lesions.

Arterial thrombi and atherosclerotic lesions were analyzed immunochemically and examined histologically. The extent of in vivo proteolytic cleavage of the amino-terminal end of fibrinogen by thrombin and plasmin was determined and quantitated by specific radioimmunoassays. The samples were treated with cyanogen bromide (CNBr), and the total amount of fibrinogen and fibrin-derived protein was determined as NDSK, the NH2-terminal disulfide knot of fibrinogen. Thrombin-releasable fibrinopeptides A and B were used to quantitate fibrinogen and fibrin I. Previous plasmin cleavage of the B beta chain was inferred from the amount of B beta 1-42 and B beta 15-42 in undigested NDSK. The results obtained in both acute and organized thrombi indicate that approximately 60% of the total protein (as determined by amino acid analysis) was fibrinogen-derived and that 70% to 80% of the fibrinogen-derived material was fibrin II. These findings support the hypothesis that fibrin II as distinct from fibrin I is the predominant component in a thrombus. In samples from normal and atherosclerotic aortas, fibrinogen-derived protein comprised less than 10% of the total protein. Samples from grossly normal aortas contained only fibrinogen and fibrin I. Fibrinogen concentration decreased and fibrin II concentration increased with increasing severity of the lesions, suggesting that increased fibrin II formation is associated with progression of atheromas.

Aorta↗
PubMed1986

Immunologic identification of the cleavage products from the A alpha- and B beta-chains in the early stages of plasmin digestion of fibrinogen.

Fragment X components (Mr 225,000 to 333,000) were distinguished on sodium dodecyl sulfate polyacrylamide gels. Western blotting with monoclonal antibodies to A alpha-chain segments demonstrated that the A alpha-chains of fibrinogen and the largest fragment X components (Mr 285,000-340,000) contained both A alpha 259-276 and A alpha 540-554. Fragment X components of Mr 270,000-285,000 contained A alpha 259-276 but lacked A alpha 540-554, whereas the smallest fragment X components (Mr 225,000-270,000) contained neither A alpha 540-554 nor A alpha 259-276. Studies of the small peptides generated during fragment X formation complemented the studies of the large molecules, by demonstrating peptides containing both A alpha 259-276 and A alpha 540-554 (Mr 41,600-41,800 and Mr 38,700-38,900), peptides containing A alpha 540-554 but not A alpha 259-276 (Mr 20,500-21,000 and Mr 17,300-17,500) and peptides containing only A alpha 259-276 (Mr 23,600-24,000 and Mr 20,500-21,000). Cleavage of B beta 1-42 from the amino terminal ends of the B beta-chains, measured with a specific radioimmunoassay, was linear until 1.6 moles per mole of fibrinogen had been released, and coincided with loss of the central and carboxy terminal A alpha-chain regions, i. e. A alpha 259-276 and A alpha 540-554. Based on present and previously reported data, a model is proposed for the evolution of the heterogeneous group of fragment X derivatives from fibrinogen with the simultaneous release of small peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1986

Plasma levels of platelet secretory proteins.

Platelets contain three types of secretory organelles: the dense granules, the alpha granules, and the lysosomes. Most of the proteins secreted from platelets are stored in the alpha granules, whereas the dense granules contain substances such as adenine nucleotides, serotonin, Ca++, and inorganic pyrophosphate types as well as a heparatinase. Three of the secreted alpha granule proteins have been measured by radioimmunoassay and it has been suggested that levels of these proteins in patient plasmas provide an index of in vivo platelet activation and secretion. These three are beta-thromboglobulin, platelet factor 4, and thrombospondin. In this chapter the chemistry of these proteins will be considered briefly, as will their clearance from the circulation, and then the clinical studies will be reviewed critically. Since radioimmunoassays were developed for these proteins (the first was reported in 1975), there has been a profusion of reports on levels of one or another of these proteins in a wide range of disease states, and these reports have indicated secreted platelet protein levels ranging from normal to grossly elevated in a given disease state. Possible reasons for such variability will be discussed.

Angina, Unstable↗
PubMed1986

The Directive Group: short-term treatment for psychiatric patients with a minimal level of functioning.

This paper describes a three-level interdisciplinary group program for treating patients on a short-term psychiatric inpatient unit. Special emphasis is given to the lowest level group, the Directive Group, which addresses the needs of patients with a minimal level of functioning, a population that is usually neglected in terms of group therapy. The author developed the Directive Group based on her own clinical experience and later refined it using the model of human occupation as a conceptual framework. Therapists have modified and refined the program since its inception in July of 1977. The benefits and limitations of the program are discussed with applications for other health care settings.

Documentation↗
PubMed1986

The expression of endothelial cell surface antigens by AIDS-associated Kaposi's sarcoma. Evidence for a vascular endothelial cell origin.

The authors investigated 19 cases of Kaposi's sarcoma (KS) obtained from patients with the acquired immune deficiency syndrome (AIDS) for their expression of Factor VIII-related antigen (FVIIIRAg), HLA-DR (Ia) antigens, OKM1, and three distinctive vascular, but not lymphatic, endothelial-cell-associated antigens, E92, OKM5, and HCl. Antigen expression was demonstrated by immunoperoxidase staining of cryostat sections. FVIIIRAg is strongly expressed by the cells lining the vascular spaces (VCs) but is absent, weakly or focally, and variably expressed by the spindle cell (SC) component of KS. The VC component of each KS lesion examined strongly expressed E92, moderately expressed HCl, and weakly expressed OKM5. In contrast, the entire SC component of each KS lesion studied strongly expressed E92 and OKM5 and weakly expressed HCl. Neither the VCs nor the SCs expressed OKM1. These studies provide strong and compelling evidence for the vascular endothelial cell histogenesis of both the vascular and spindle cell components of KS, demonstrate the intertumor and intratumor phenotypic heterogeneity of KS, and suggest that monoclonal antibodies OKM5 and anti-E92 are the best currently available immunohistochemical markers for identifying the spindle cell component of AIDS-associated KS in cryostat sections.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Nomenclature of secreted platelet proteins--report of the Working Party on Secreted Platelet Proteins of the Subcommittee on Platelets.

Standard nomenclature for a number of secreted platelet proteins was agreed upon by The Working Party on Secreted Platelet Proteins of the Subcommittee on Platelets. Platelet factor 4 will continue to be used for the molecule with high heparin affinity, subunit molecular weight of 7780, and the described amino acid sequence. beta-Thromboglobulin will be used to designate beta-Thromboglobulin (81 amino acids/subunit, beta-mobility on cellulose-acetate electrophoresis, pI 7), low-affinity platelet factor 4 (85 amino acids/subunit, gamma-mobility on cellulose-acetate electrophoresis, pI 8), and platelet basic protein (94 amino acids/subunit, pI 10) when these are measured immunologically in plasma, but that thromboglobulin with a superscript designation of the pI should be used when assays are conducted on samples after isoelectric focusing, and a subscript amino-terminal amino acid can be added when a purified protein is described. Thrombospondin will continue to be the designation for the high molecular weight trimer that has previously been called thrombospondin or glycoprotein G. Platelet derived growth factor will be used for the group of closely related proteins of molecular weight about 30,000 and isoelectric point about 10.

Animals↗
PubMed1985

The Hermansky-Pudlak syndrome. Report of three cases and review of pathophysiology and management considerations.

Three Puerto Rican siblings with the Hermansky-Pudlak syndrome are described, and the literature on this syndrome is reviewed with regard to clinical factors, pathology, pathophysiology, and management of the disorder. The three patients all manifested oculocutaneous albinism and platelet storage pool disease with a moderate bleeding tendency. The oldest sibling died from restrictive lung disease and another has evidence of reduced functional residual capacity, although he is asymptomatic. None of the patients had evidence of inflammatory bowel disease, which has been reported in some cases. All of the patients had an increased incidence of bacterial infections, and they were anergic. Whether their immunological defect(s) is related to the Hermansky-Pudlak syndrome is not known. Two of the patients were treated with oral vitamin E. Bleeding symptoms in both were markedly reduced, although major changes in platelet aggregation were not seen. Vitamin E therapy did not appear to affect the progression of lung disease in the patient with fatal restrictive lung disease.

Adult↗
PubMed1984

Prostacyclin production by perturbed bovine aortic endothelial cells in culture.

This study reports that endotoxin (Escherichia coli serotype 026:B6) and 12-O-tetradecanoyl-phorbol-13-acetate stimulate cultured bovine aortic endothelial cells to generate prostacyclin. The prostacyclin concentration of the culture medium was measured indirectly by radioimmunoassay for 6-keto-PGF1 alpha. The amount of prostacyclin generated depended on the concentration of endotoxin or phorbol diester. Prostacyclin generation was not immediate, but occurred slowly after a six-hour lag period. The perturbed cells contracted and showed marked shape changes that correlated temporally with the start of enhanced prostacyclin production. Cytochalasins B and D, vinblastine, and colchicine inhibited prostacyclin production, indicating involvement of the cytoskeleton in the cellular response to endotoxin and phorbol diester. The increase in prostacyclin production was prevented by trifluoperazine, an inhibitor of the Ca++-calmodulin system, which is known to be involved in cytoskeletal function. Generation of prostacyclin was inhibited by cycloheximide and actinomycin D, indicating dependence on protein and ribonucleic acid synthesis. It is postulated that exposure to endotoxin or phorbol diester leads, via a series of reactions that involve RNA and protein synthesis and require intact cytoskeletal function, to the generation of toxic active intermediate(s) that stimulate the enzymes necessary for prostacyclin production.

Animals↗