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Biomedical subjects

H L Messmore

Publications and source records attributed to H L Messmore.

At least 55 records · Page 3Linked to original sources
PubMed1985

Expression of a monocyte-specific esterase isoenzyme in cases of acute myeloid leukemias.

The carboxylic esterase (E.C. 3.1.1.1) isoenzymes from cases of acute myeloid leukemias were separated by analytical isoelectric focusing on horizontal thin-layer gels. One isoenzyme consisting of one or two components (bands) could be completely and selectively inhibited by addition of 40 mM sodium fluoride (NaF) to the staining bath. The 105 cases were classified into the groups M1-M6 according to the FAB proposals. The NaF-sensitive isoenzyme was not detected in cases of FAB groups M1/2 (acute myeloblastic leukemia without or with maturation), group M3 (acute promyelocytic leukemia) or group M6 (erythroleukemia). Thirty-one out of 33 cases in the FAB group M4 (acute myelomonocytic leukemia) and 9/9 cases in FAB group M5 (acute monocytic leukemia) expressed the NaF-sensitive isoenzyme. The NaF-sensitive isoenzyme was found at different staining intensities; all M5 cases showed the isoenzyme at strong or very strong intensity, whereas most of the M4 cases displayed the isoenzyme at weak, medium or strong staining intensity. The data presented are further evidence that the presence of the NaF-sensitive esterase isoenzyme indicates monocytic involvement or differentiation in cases of myeloid leukemias. The easy and fast to perform method of isoelectric focusing can be used to distinguish the monocytic variants among the acute myeloid leukemias and can supplement the morphological analysis of these cases.

Carboxylic Ester Hydrolases↗
PubMed1985

Studies on the profibrinolytic actions of heparin and its fractions.

Utilizing modified immunochemical methods (ELISA and radioimmunoassay) tissue plasminogen activator, B beta 15-42 RPs and protein C antigen levels were measured in man and a subhuman primate model after subcutaneous and intravenous administration of various low molecular weight heparin fractions. A wide scatter in the data was observed in the t-PA and B beta 15-42 RP levels; however, statistical analysis of the data revealed that certain low molecular weight heparin fractions increased the levels of these endogenous markers of fibrinolysis. No significant alteration in the protein C levels was noted at any time; however, a wide scatter in these data was also evident. The profibrinolytic actions of low molecular weight heparin fractions may be related to the release of t-PA, which is easily measured in plasma. Since it has strong affinity for endogenous sites (thrombus, surface), wide scatter in the data may occur. Physical exercise may also increase the levels. Most of the results reported in our studies represent data on blood samples that were obtained using the simple venipuncture method. We also find that the intravenous administration of the low molecular weight heparin fractions also caused a shortening of the ELT. Since the low molecular weight heparin fractions are heterogeneous in nature, the profibrinolytic actions may be related to one or more of these constituent fragments. Thus, the molecular identity of the profibrinolytic component of low molecular weight fractions remains unknown at this time. Also unknown is if there is a relationship between this effect and anticoagulant activity.

Animals↗
PubMed1984

Diagnostic efficacy of a simple radioimmunoassay test for fibrinogen/fibrin fragments containing the B beta 15-42 sequence.

A simple RIA method for B beta 15-42 RPs has been evaluated in our laboratory to investigate experimental and clinical fibrinolytic states. The assay utilizes bentonite precipitation to remove cross-reacting fibrinogen. Due to the heterogeneity in molecular weights of the B beta RPs, the results are expressed as nanograms per milliliter. The linear range of the assay is 2 to 40 ng/ml, with a capability of detecting up to 200 ng/ml. A special anticoagulant mixture (heparin or EDTA/aprotinin) is required for sample collection. Certain precautions in the care and handling of specimens are also necessary. Increased levels of B beta RPs were observed in the following conditions: malignancy (associated with increased release of tissue plasminogen activators), pancreatitis, liver diseases, pregnancy, and postexercise testing (associated with increased release of tissue plasminogen activators). Increased levels of B beta RPs were also found during thrombolytic therapy, anabolic steroid treatment, prothrombin complex concentrate therapy, blood component therapy, and low molecular weight heparin subcutaneous therapy (associated with an increase in tissue plasminogen activator release). Our studies suggest that B beta RPs are sensitive molecular markers of the endogenous activation of fibrinolytic system and may provide useful diagnostic information on a pathologic process that often remains undetectable by routine laboratory methods.

Evaluation Studies as Topic↗
PubMed1984

Molecular markers of contrast media-induced adverse reactions.

Currently used routine laboratory screening methods are not reliable in the prediction of contrast media-related adverse reactions. Cost-effective laboratory methods for various molecular markers of pathophysiologic activation have now become available. In vitro activation tests in high-risk patients may prove to be useful in the prediction of contrast-induced activation of various adverse reactions. If prior clinical evaluation of a patient suggests an ongoing pathologic process, profiling of the following molecular markers may prove to be useful and helpful in avoiding contrast-induced adverse reactions: Fibrinopeptide A, platelet factor 4, thromboxane B2, 5-HETE, physiologic inhibitors of proteases, B beta 15-42 related peptides, bradykinin/kininogen, and anaphylactozins. In patients suspected of reacting to contrast agents, a small dose of 1 to 5 ml can be injected as a bolus and molecular marker profiling on blood drawn after the infusion may prove to be useful screening tests. Additional clinical studies are needed to prove this. However, this screening test should be performed with extreme caution, since some of the patients are known to react to as little as 1 ml dose. The safety of newly developed nonionic contrast agents can be readily assessed by profiling various molecular markers of adverse reactions, which provide a more reliable and quantitative assessment of contrast-induced adverse reactions. Based on molecular marker profiling, various prophylactic agents can be given to high-risk patients to avoid contrast-induced adverse reactions.

Angiocardiography↗
PubMed1984

Myocardial infarction and severe thromboembolic complications. As seen in an estrogen-dependent transsexual.

An estrogen-dependent genetic-male transsexual had an extensive anterior wall myocardial infarction, despite insignificant coronary artery disease, a subsequent mural thrombosis, and resultant multiple cardioarterial thromboembolic events, despite heparin therapy. With an otherwise lack of cardiac risk factors, the patient was demonstrated to have an antithrombin III deficiency that resolved when conjugated estrogen therapy was withdrawn. Although congenital, plasminogen-activator dysfunction, or heparin-induced etiologies could not be ruled out, we believe this case demonstrated an estrogen-induced-antithrombin III deficiency culminating in thrombotic diathesis. This identifies a previously unrecognized population at risk. Prophylactic and therapeutic considerations are discussed.

Adult↗
PubMed1983

Synthetic peptide substrates in hemostatic testing.

Since the introduction of synthetic chromogenic and fluorogenic peptide substrates from serine proteases, the testing of coagulation has undergone a dramatic conceptual and methodological change. The concept of coagulation profiling has emerged and automated methodologies are being introduced. Synthetic substrate methods for the evaluation of antithrombin-III; progressive antithrombin; plasminogen; antiplasmin; prekallikrein; antikallikrein ; alpha 1-antitrypsin; prothrombin; heparin; platelet factor IV; urokinase; tissue activator of plasminogen; factor assays; amidolytic equivalents of prothrombin time; and partial thromboplastin time have been developed. Studies on antithrombin-III indicate that immunological methods evaluate the total immunoreactive-antithrombin-III (antigenic) level and do not discriminate between functionally active forms and the AT-III serine protease complex. The clinical significance of AT-III measured by immunological methods is highly questionable. The coagulant assays for the measurement of AT-III require purified alpha-thrombin preparations. The noncoagulant forms of thrombin (beta- and gamma-) result in falsely low antithrombin-III quantitation. The molecular heterogeneity in a given thrombin preparation if standardized in terms of its amidolytic activity does not produce any errors in the quantitation of AT-III levels with synthetic peptide methods. None of the immunological methods provide clinically relevant information except in normal plasma where the immunological and functional activities are identical. Analysis of pathologic plasma samples using laser nephelometry, radial immunodiffusion and radioimmunoassay methods revealed that the functional activity of various serine protease inhibitors is greatly reduced but the reduction in the immunological quantities is minimal. Since coagulation proteins are functional, a ratio between their functional activity and absolute protein levels may be a useful parameter. Employing human and bovine thrombin; bovine and human Xa with their respective substrates, the absolute quantitation of heparin is satisfactorily carried out, however, these assays only measure heparin concentrations and do not reflect the overall anticoagulant effect of heparin. Using the synthetic substrates, the value of measuring absolute concentrations of heparin in a patient on heparin therapy is questionable. With the introduction of fluorogenic substrates, the presence of activated coagulation factors may be demonstrated in patients with thrombotic disorders.(ABSTRACT TRUNCATED AT 400 WORDS)

Anticoagulants↗
PubMed1983

Impact of automation on the quantitation of low molecular weight markers of hemostatic defects.

Through in depth studies, the biochemical pathways of hemostasis-related systems have been elucidated in terms of well-defined molecular mechanisms. The interrelationships of coagulation, fibrinolytic, kallikrein-kinin, platelets, prostaglandins, blood vessel, and complement systems are now well understood. Methods are currently developed to quantitate the molecular markers of each of these systems and define the involvement of each in disease and drug-related aberrations. Molecular markers allow for very early detection of disease states well before clinical manifestations are seen or current coagulation methods are affected. Therefore prophylactic or therapeutic treatment can begin before a disease state causes damage. Platelet factor 4 and beta-thromboglobulin are low molecular weight proteins released from the light (alpha) granules of platelets and provide a reliable index of endogenous activation and consumption of platelets. Serotonin and ADP are released during activation from the beta-granules and can be measured by high-performance liquid chromatography. Fibrinopeptide A is a molecular marker of the activation of the coagulation process and provides a useful index of the action of thrombin on fibrinogen. Elevated levels of this peptide are found in patients with hypercoagulable states or a thrombotic tendency. B beta 15-42 peptides are released at the early stages of fibrinolysis and are a useful collective parameter for the measurement of the activation of fibrinolysis. In both the primary and secondary fibrinolytic disorders this peptide is elevated. Circulating kinins provide information on the activation of the kallikrein system and are useful in monitoring coagulation and shock related disorders. Arachidonic acid metabolites, such as thromboxanes and prostacyclins, are products of platelet and vascular endothelium interactions. Their measurement in peripheral blood provides a useful tool to measure the vascular and platelet-related thrombotic defects. Furthermore, antiplatelet therapy can be monitored using these parameters. Numerous other metabolites of arachidonic acid such as the leukotrienes and PAFs also are generated in various immunopathologic disorders associated with hemostatic activation. Unlike the other coagulant tests, the measurement of molecular markers in native blood or plasma samples provides a true picture of the endogenous physiology. Since no activator or additive is added to influence the test, these markers provide the most relevant information on the pathophysiologic condition. Since most of these markers are proteins or low molecular weight products, isotopic and nonisotopic immunoassays, high performance liquid chromatography and fluorometric methods can be used to analyze their levels. Furthermore, multiple panels can be developed to profile various pathologic states.(ABSTRACT TRUNCATED AT 400 WORDS)

Arachidonic Acid↗
PubMed1983

Newer avenues in the monitoring of antithrombotic therapy: the role of automation.

In the future, we may find that antithrombotic therapy provides its major effects other than by Factors Xa and IIa inhibition, in which case a panel of assays may be of clinical use to determine how a given patient is responding to therapy. All methods discussed previously for direct factor assays, global tests, or specific factor inhibition can be modified for synthetic substrates. With instruments such as the IL Multistat III centrifugal analyzer, which has detection capabilities for visible light, fluorescence and light scatter, it will be possible to panel profile synthetic substrate-based assays, immunologic assays (for example, platelet release products or circulating complexes of enzyme-inhibitor, such as thrombin-AT III) and possibly platelet aggregations/luminescence in one rotor. The field of coagulation is rapidly expanding in the development of newer tests to measure newly discovered proteins (protein C), development of new drugs and therapeutic regimens, and incorporating immunologic and enzymologic technologies and clinical chemistry standardization and quality control practices. Throughout this period of growth, automation has been in the forefront and is playing an ever-increasing role in every old and new aspect of coagulation evaluation. We are aware of the advantages that accompany any automated device over manual techniques, so there should be much hope and expectation for the new hemostasis and thrombosis laboratory.

Administration, Oral↗
PubMed1983

Diagnostic efficacy of newer synthetic-substrates methods for assessing coagulation variables: a critical overview.

With the introduction of synthetic substrates, many newer methods have been developed for testing coagulation parameters. Some of these methods are used in clinical settings, and many have been evaluated for their diagnostic efficacy in various coagulation disorders. Clinical chemistry laboratory instrumentation has been used to accommodate these methods. Commercially available kits for antithrombin III, heparin, plasminogen, alpha 2-antiplasmin, and factor X are used by many laboratories. Individual reagents have also become available and are being used to develop assays for routine diagnostic use. The development of suitable standards is rapidly underway, and their availability will facilitate adoption of these methods by hospital laboratories. Many of the synthetic-substrate-based assays that have been introduced for routine diagnostic purposes have been published recently. Here, we provide an overview of the newer amidolytic methods for the measurement of certain coagulation variables.

Anticoagulants↗
PubMed1982

Ionic and non-ionic contrast media interaction with anticoagulant drugs.

Normal and pathologic human plasmas were incubated with radiographic contrast media, heparin, Dextran-40 and saline. Renografin-60 produced a strong anticoagulant effect and the clotting times were significantly prolonged; the addition of heparin resulted in greatly elevated thrombin time. No such prolongation was noted with Dextran-40. P-297, ioxaglic and ioxithalamic acids also showed similar anticoagulant properties. When dogs were injected with contrast media and heparin, the overall anticoagulant effect lasted for more than 6 hours, while contrast media or heparin effect remained for a short period of time. Clinical significance of contrast media interactions with anticoagulant drugs is discussed.

Animals↗