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Biomedical subjects

J C Mattson

Publications and source records attributed to J C Mattson.

At least 19 recordsLinked to original sources
PubMed1999

Correlation of activated clotting time and activated partial thromboplastin time to plasma heparin concentration.

STUDY OBJECTIVE: To determine the correlation between activated clotting time (ACT) or activated partial thromboplastin time (aPTT) and plasma heparin concentration. DESIGN: Two-phase prospective study. SETTING: University-affiliated community hospital. PATIENTS: Thirty patients receiving continuous-infusion intravenous heparin. INTERVENTIONS: Measurement of ACT, aPTT and plasma heparin concentrations. MEASUREMENTS AND MAIN RESULTS: Linear and log linear correlations were determined between clotting time tests and heparin concentrations. Linear correlations yielded r values of 0.58 for ACT (p=0.008) and 0.89 for aPTT (p=0.0001). Log linear correlations yielded r values of 0.60 for ACT (p=0.005) and 0.88 for aPTT (p=0.0001). A decision analysis was performed to determine possible consequences of dosage adjustments based on either test in relationship to the decision based on plasma heparin concentration. The decision analysis based on ACT disagreed with corresponding decisions based on plasma heparin concentration in 15 of 30 patients; 13 disagreements may have increased the risk of bleeding, and the other 2 may have increased the risk of thrombosis. Decisions based on aPTT disagreed with corresponding decisions based on plasma heparin concentration in 13 of 30 patients; 2 disagreements may have increased the risk of bleeding, and the other 11 may have increased the risk of thrombosis. CONCLUSION: There are significant statistical linear and log linear correlations between both clotting time tests and plasma heparin concentrations, with aPTT showing stronger correlation than ACT. However, decisions regarding heparin therapy based on ACT may increase a patient's risk of bleeding, whereas decisions based on aPTT may increase the risk of thrombus progression or rethrombosis.

Aged↗
PubMed1997

Monitoring platelet glycoprotein IIb/IIIa-fibrin interaction with tissue factor-activated thromboelastography.

Computerized thromboelastography (TEG) was used to study platelet glycoprotein IIb/IIIa function, characterize the consequences of the interaction between polymerizing fibrin and activated platelets, and establish a quantitative assay of platelet function. The ability of platelets to augment the shear elastic modulus of blood clots was measured by TEG under conditions of maximal platelet activation during ex vivo clot formation accelerated by recombinant human tissue factor (TF). Under these conditions, platelets significantly enhance clot strength eightfold (relative to platelet-free fibrin clots). This effect, inhibited by cytochalasin D and c7E3 Fab, appears to be dependent on the transmission of platelet contractile force to fibrin, through glycoprotein IIb/IIIa receptors. The c7E3 Fab dose response of TF-TEG clot strength is identical to results with platelet aggregation induced by the thrombin receptor agonist peptide (50% inhibitory concentration (IC50 = 3.6 microg/ml); adenosine diphosphate-induced aggregation is easier to inhibit (IC50 = 1.2 microg/ml). The results obtained with this system are reproducible (coefficient of variation for clot strength 4%; intraclass correlation coefficient 0.96). As a clinical assay, TF-triggered computerized TEG is easy to perform at the bedside, provides on-line results within 30 minutes, and may offer advantages over conventional measures of platelet function.

Abciximab↗
PubMed1996

bcr gene rearrangement analysis in myeloproliferative disorders other than chronic myelogenous leukemia.

The bcr gene rearrangement resulting from the Philadelphia translocation is diagnostic of chronic myelogenous leukemia (CML) and is considered the hallmark of this myeloproliferative disorder (MPD) at the molecular level. The other MPDs, essential thrombocythemia (ET), polycythemia vera (PV), agnogenic myeloid metaplasia (AMM), and unclassified MPD, share morphologic features with CML, making the diagnosis difficult in cases with considerable morphologic overlap. In such cases, molecular analysis becomes essential for accurate diagnosis. We report results of bcr analysis by Southern hybridization in 37 patients with MPDs other than CML: ET (20 cases), PV (seven cases). unclassified MPD (nine cases), as well as in one case of chronic myelomonocytic leukemia (CMML). bcr negativity ruled out CML in 36 cases, confirming the morphologic diagnosis. In one case diagnosed as ET. bcr gene rearrangement was diagnostic of CML. The correct diagnosis made possible a different therapeutic approach in this young patient and resulted in cure after allogeneic bone marrow transplantation. The existence of such cases makes the use of molecular analysis essential in the evaluation of MPDs, even when the morphologic features do not unequivocally support the diagnosis of CML, as in this patient.

Adult↗
PubMed1995

Discordant morphologic features in bone marrow involvement by malignant lymphomas: use of gene rearrangement patterns for diagnosis.

Discordant morphology between lymph node or extra-nodal site and bone marrow (BM) involvement by non-Hodgkin's malignant lymphoma (NHL) is a common occurrence, causing diagnostic difficulties. Additional diagnostic problems are posed by lymphoid aggregates commonly found in the BM of elderly patients, the age group with the highest incidence of lymphoma. Morphologic features are used to distinguish between benign and malignant lesions but no feature is diagnostic and exceptions are numerous. Immunophenotyping is helpful for detecting B cell monoclonality, but it cannot detect T cell monoclonality. Unique B and T cell gene rearrangement patterns, the molecular "signature" of the lymphoma, can be used to detect monoclonal lymphoid populations. Finding the same rearrangement pattern in the BM as in the primary mass is proof of BM involvement by the same clone of malignant cells. We used B/T and Bcl-2 gene rearrangements to help diagnose cases with discordant morphology between primary site and BM. One hundred and seventy-five specimens, obtained from patients undergoing staging or restaging for NHL, were analyzed for B/T cell and Bcl-2 gene rearrangements by multiple restriction endonuclease digestion and Southern hybridization with 32P labeled JH, JK, CT beta, and Bcl-2 probes. Forty-two specimens (24%) from 24 patients showed discordant morphology: of 13 specimens with atypical lymphoid aggregates, only one had B cell gene rearrangement; of 15 specimens with morphologically benign lymphoid aggregates, one demonstrated B cell gene rearrangement; and of 14 specimens positive for NHL with different morphology than the lymph node, 13 were positive for B cell gene rearrangements. Molecular analysis can aid in the diagnosis of NHL, can establish a "baseline" for detection of recurrence, and is useful in monitoring therapy. These data suggest that it is also a tool for the pathologist in cases of discordant morphology between the primary tumor and BM, and should be strongly considered for each site.

B-Lymphocytes↗
PubMed1995

Separate clones in concomitant multiple myeloma and a second B-cell neoplasm demonstrated by molecular and immunophenotypic analysis.

The occurrence of multiple myeloma (MM) and a second B-cell neoplasm in the same patient is a rare event. We present 2 such patients, and provide evidence to support the presence of separate clones in these coexisting neoplasms. In the first case, MM became evident 14 months after the diagnosis of chronic lymphocytic leukemia (CLL). In past reports, most occurrences of this association, when investigated, have been regarded to be biclonal disease processes; however, with few exceptions, most were documented by immunologic studies alone. To establish the clonality in our case of CLL with MM, we examined both immunophenotypic data obtained by standard two-color flow cytometric analysis, and patterns of immunoglobulin gene rearrangement, using standard Southern analysis and hybridization with 32P-labelled JH and JK probes. This provided evidence for the presence in this patient of two separate monoclonal populations of B cells, manifested as light chain restrictions and gene rearrangements which differed in blood (CLL) and bone marrow (MM) samples. In the second case, MM presented simultaneously with bone marrow lymphocytosis and abnormal peripheral lymphocytes. Clonality studies on blood were not done. Bone marrow B-cell gene rearrangement studies, however, revealed the presence of three bands in the JK blot of significantly different intensities, suggestive of two monoclonal populations. A monoclonal population of small cells with surface B markers and surface IgM was demonstrated by flow cytometry, while a second population of larger cells with intracytoplasmic IgG matching the patient's serum monoclonal protein was detected by immunofluorescence microscopy. The results in these 2 cases expand previous findings of the rare association of MM with a second B-cell neoplasm, and demonstrate the usefulness of molecular diagnostic investigation.

B-Lymphocytes↗
PubMed1995

Effect of resuscitation solutions on the immune status of dogs in hemorrhagic shock.

The purpose of this study is to examine the effects of three different types of fluid resuscitation on the immune system of dogs in hemorrhagic shock. Using a modified Wigger shock model, 18 conditioned male dogs were bled to mean arterial blood pressure of 60 mm Hg for 90 minutes and placed into three groups based on the resuscitative method. Group I: Crystalloid Resuscitation; Group II: Autotransfusion; Group III: Banked Blood. Laboratory methods for immune status evaluation included total lymphocyte count, T4/T8 ratio, total serum immunoglobulins, and immunoglobulin electrophoresis. These values were obtained pre-hemorrhagic shock, just before resuscitation, and subsequently on days 1, 4, and 7. Humoral immunity, represented by total serum immunoglobulin levels (IgA, IgG, IgM), was higher in Groups II and III when compared with group I on all post-resuscitation days. IgA and IgM levels were higher in Group III compared with Groups I and II. IgG level was higher in Group II compared with Groups I and III. Cellular immunity was also affected by transfusion. Total lymphocyte count was increased in Group II on Day 1; however, the three groups were similar with respect to this variable on subsequent days. The absolute T4 helper cell level in Group II was similar to Groups I and III until Day 7, at which time the level became higher in Group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Retrospective DNA analysis using fixed tissue specimens.

The recent explosion of scientific and technical knowledge in the field of molecular biology has allowed us to make important advances in our understanding of the molecular basis of many human diseases. This technology has now entered the clinical laboratory where identification of specific genetic sequences can aid in the precise diagnosis of hematologic and other malignancies, inherited diseases, specific infectious agents, and inherited predisposition to disease. In addition, it can be applied to prenatal diagnosis, paternity testing, identification of minimal residual disease following treatment, and assessment of drug sensitivity or resistance. In many cases in diagnostic pathology, the need for molecular analysis often is not realized until after a critical tissue specimen has been fixed, embedded, and examined microscopically. Thus, there is a clear need for development of techniques that would allow the retrospective study of archival tissues that have been fixed and embedded in paraffin. This review examines in depth those factors which influence the quality of the DNA available from fixed embedded tissues and discusses the usefulness of polymerase chain reaction amplification in obtaining sufficient diagnostically useful DNA from archival specimens. It is hoped that this review will aid the diagnostic pathologist interested in the application of molecular techniques in the retrospective study of fixed embedded tissues.

DNA↗
PubMed1992

Amplification of intermediate-size DNA sequences from formalin and B-5 fixed tissue by polymerase chain reaction.

Retrospective analysis of DNA from paraffin-embedded fixed bone marrow biopsy specimens is possible if preceded by amplification of the DNA sequences of interest by the polymerase chain reaction (PCR). These fixed specimens yield degraded DNA that may not be suitable for direct analysis by conventional digestion and hybridization methods. This limitation is circumvented by PCR amplification and subsequent analysis of the amplified products. The model used in this study is the amplification of a 725 base-pair (bp) beta-globin gene sequence encompassing the sickle-cell anemia point mutation, followed by Cvn I digestion. The beta A beta A, beta A beta S, and beta S beta S genotypes are derived from analysis of the allele-specific digestion patterns. Two fixatives were compared: neutral-buffered formalin and a mercury-based fixative (B-5) routinely used for bone marrow biopsies. DNA extracted from B-5-fixed bone marrow specimens was found to be more degraded than DNA from neutral-buffered, formalin-fixed bone marrow aliquots from the same specimens. PCR amplification of the 725 bp beta-globin gene sequence was successful with DNA from formalin-fixed bone marrow specimens, but not with DNA from B-5-fixed identical specimens. Analysis of the amplified product by Cvn I digestion resulted in correct genotype derivation for all patients, normal controls and positive controls (patients diagnosed with sickle-cell anemia or trait). These results indicate that intermediate-size DNA sequences can be amplified and analyzed when DNA is extracted from formalin-fixed bone marrow specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Sickle Cell↗
PubMed1991

Chronic granulocytic leukemia: reassessment of morphologic and cytogenetic characteristics in Ph1-positive and Ph1-negative cases.

33 cases of chronic granulocytic leukemia (CGL) were reassessed to determine if, by strict morphologic criteria. Philadelphia chromosome (Ph1)-negative CGL exists as a diagnostic entity and if Ph1-positive CGL could be distinguished from Ph1-negative CGL. Cases were reassessed using published criteria and, of 11 Ph1-negative cases, only 4 could be reclassified as myelodysplastic syndromes or undifferentiated chronic myeloproliferative disorder. Of the morphologic parameters evaluated, peripheral blood basophilia and bicytopenia proved to be good discriminators between Ph1-positive and Ph1-negative cases. As a group, Ph1-negative cases were more heterogeneous and tended to have lower hemoglobin, WBC, platelet count and absolute eosinophilia. Chromosomal abnormalities other than Ph1 were seen only in the Ph1-positive cases. Based on these findings, we conclude that Ph1-negative CGL constitutes a heterogeneous group, a subgroup of which is morphologically identical with the Ph1-positive CGL. The parameters that best discriminate between Ph1-positive and Ph1-negative cases are peripheral blood absolute basophilia and bicytopenia.

Adolescent↗
PubMed1991

A comparison of the fibrinogen receptor distribution on adherent platelets using both soluble fibrinogen and fibrinogen immobilized on gold beads.

The distribution of fibrinogen receptors was determined on the surface of adherent platelets using both direct labeling with the ligand fibrinogen which was immobilized on gold particles (Fg-Au) and indirect immunogold (Ig-Au) labeling of bound soluble fibrinogen identified with a rabbit polyclonal anti-fibrinogen antibody. Two distinctly different patterns of labeling were obtained and appeared to depend on whether solid phase fibrinogen (Fg-Au) or soluble phase released fibrinogen were bound to the membrane receptor. The membrane-bound Fg-Au reorganized in patterns that closely mimicked the organization of the underlying cytoskeleton. In approximately 18% of the adherent platelets, Fg-Au was seen in channels or vesicle-like structures lying deep to the platelet surface suggesting internalization into the open canalicular system and/or endocytosis. The labeling pattern obtained when identifying the location of membrane-bound soluble released fibrinogen by Ig-Au was diffuse and lacked the organizational patterns characteristic of Fg-Au. Unlike the Fg-Au probe, early dendritic platelets were heavily labeled by the soluble phase fibrinogen using the Ig-Au technique. Although the label covered the entire exposed platelet membrane in fully spread platelets, labeling over the peripheral web was more dense than that over the intermediate or granulomere zone. The diffuse organization and heavier peripheral distributional pattern of the glycoprotein IIb-IIIa (GP IIb-IIIa) receptor in fixed, adherent platelets, was also seen with the GP IIb-IIIa receptor-specific antibody AP-2. The binding of both the Fg-Au and Ig-Au were inhibited using the tetrapeptide Arg-Gly-Asp-Ser (RGDS) (93% and 98% inhibition, respectively), AP-2 (98% and 97%, respectively) and platelets from patients with Glanzmann's thrombasthenia (GT) (99% and 98%, respectively). The data presented provides the first report that receptor reorganization, following binding of fibrinogen, appears to be related to the state of the ligand. Substrate bound fibrinogen (i.e., Fg-Au or fibrinogen bound to another platelet) induces receptor translocation toward the platelet granulomere in a capping-like phenomenon. On the other hand, the binding of soluble released fibrinogen results in formation of microclusters and short linear arrays in a diffuse distribution but does not induce central movement of receptors. Furthermore, double labeling studies clarify that Fg-Au does not identify all available fibrinogen receptors as many are occupied by soluble released fibrinogen. The data presented provides an interesting new perspective on what constitutes an appropriate ligand-receptor stimulus sufficient to induce receptor reorganization.

Amino Acid Sequence↗
PubMed1990

Polymerase chain reaction: amplification of DNA from fixed tissue.

The polymerase chain reaction (PCR) allows the analysis of DNA from biologic samples containing only nanogram quantities of DNA. We used DNA purified from fresh or frozen peripheral blood (PB) leukocytes and formalin, or B-5 fixed bone marrow aspirate clots (BM). A sequence of the beta-globin gene was amplified via the PCR then hybridized with allele specific oligonucleotide probes for hemoglobin A, S, and C. All DNA preparations, including formalin and B-5 fixed BMs, were successfully amplified; the hybridization of the amplified products resulted in patterns consistent with the hemoglobin phenotype for all patients. PCR can be used on DNA from many sources; retrospective studies using paraffin embedded fixed tissue are possible because extremely small amounts of DNA present in fixed tissue can be successfully amplified.

Adult↗
PubMed1986

Defective contact activation of platelets from dogs with basset hound hereditary thrombopathy.

Basset Hound Hereditary Thrombopathy (BHT) is an autosomally inherited disorder of platelet function characterized by a thrombasthenia-like defect in aggregation but normal clot retraction. Glycoprotein IIb-IIIa (GP IIb-IIIa) is detectable in BHT platelets but may be functionally defective. In order to further characterize this potential model for human Glanzmann's thrombasthenia, contact reactivity of BHT platelets was studied by whole mount electron microscopy. Gel filtered BHT platelets, after 30 minutes of contact activation, attached poorly to a formvar substrate. There was an 8 fold difference in the number of adherent BHT platelets and normal platelets. In addition, contact induced shape change was inhibited when compared to control dogs. Almost 95% of control platelets reached fully dendritic or spread forms after 30 minutes of contact; in contrast only 63.7% of BHT platelets reached this degree of activation. The addition of 8.2 uM ADP to BHT platelets induced nearly a 4 fold increase in the number of spread forms and a 5 fold increase in the number of adherent BHT platelets, but did not cause aggregate formation. Both the defect in adhesion and shape change and the ability of ADP to stimulate both adhesion and contact-induced shape change in BHT platelets are similar to recent observations in our laboratory in patient's with type II Glanzmann's thrombasthenia.

Adenosine Diphosphate↗
PubMed1985

Use of scanning electron microscopy to study structural-functional relationships in normal and diseased platelets.

This paper reviews the contribution of scanning electron microscopy (SEM) to our understanding of platelet physiology and pathology. Observations of platelet shape changes which accompany activation and the ability to visualize and analyze platelet aggregation and adhesion in three dimensions make this experimental medium an important tool in the evaluation of healthy and diseased platelets. While SEM adds a valuable third dimension to the study of morphology and ultrastructure, its greatest contribution is realized when studies are correlated directly with light and/or transmission electron microscopic observations and with studies of functional capacity.

Adenosine Diphosphate↗
PubMed1984

Clinicopathological correlations of disseminated intravascular coagulation in patients with head injury.

To try to define the significance of disseminated intravascular coagulation (DIC) in head-injured patients, we correlated clinical, laboratory, and pathological findings in 16 patients with head injury as their main problem who had DIC, who died within 4 days of injury, and who were examined postmortem. Patients were ranked according to the number of abnormal laboratory screening tests for DIC and the severity of these abnormalities. The most frequently abnormal laboratory tests were the fibrinogen degradation products and fibrinogen, followed in order by the activated partial thromboplastin time, prothrombin time, and thrombin time. The platelet count was the least abnormal value. The patients with the fewest abnormalities had the least abnormal computed tomographic scans. Autopsy reports revealed necrosis and bleeding in the brain and in a number of other organs, particularly the lungs. Microthrombi were not reported in the original autopsy reports. However, when these cases were reevaluated and their slides were stained with an immunoperoxidase technique using rabbit anti-human fibrinogen antiserum, microthrombi were seen frequently. Large microthrombi were more common in patients who had died within less than 24 hours, suggesting a relationship to death or to less time for lysis. In order of frequency, the brain/spinal cord, liver, lungs, kidneys, and pancreas were most commonly affected, and the liver, pituitary gland, pancreas, thymus, brain/spinal cord, large intestine, kidneys, and lungs had the greatest density of microthrombi. Pulmonary dysfunction had been a frequent problem in these patients, which may have been related to the high incidence of microthrombi and bleeding found in the lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Tests↗
PubMed1984

The Bernard-Soulier platelet: I. Correlation of adhesion defects with abnormalities of surface glycoproteins.

Bernard-Soulier disease, an inherited human platelet disorder, is characterized by decreased adhesion of platelets to the subendothelium. A review of the clinical features, laboratory diagnostic features and glycoprotein abnormalities is presented. The glycoprotein composition of platelets from patients with Bernard-Soulier disease was compared with normal using 3H-labeling of surface glycoproteins followed by two-dimensional gel electrophoresis. Decreased amounts of 3H-labeling of glycoprotein IIa as well as absence of the specific surface glycoprotein Ib was observed in Bernard-Soulier platelets. Studies of Bernard-Soulier platelets affords an opportunity to understand the mechanisms of platelet adhesion responses in the interactions of platelets with blood vessels.

Blood Platelet Disorders↗
PubMed1984

The Bernard-Soulier platelet: II. A comparative study of changes in platelet morphology and cytoskeletal architecture following contact activation.

Platelet adhesion is a critical, early event in hemostasis. It is a complex process which involves platelet sticking, activation, granule release, and a series of morphologic changes which appear to enhance contact. The membrane glycoprotein (GP) Ib, which is thought to play an important role in adhesion, is missing in the Bernard Soulier Syndrome (BSS) and platelets in this syndrome have a structural defect which results in giant size on peripheral smear. Correlative SEM/TEM studies on adherent BSS platelets were used to address two questions: 1) Does the absence of GP Ib in BSS platelets result in abnormalities in the morphologic changes which ordinarily accompany adhesion to formvar? and 2) Is the giantism seen in BSS platelets related to or reflected in abnormalities in organization of the cytoskeletons of adherent platelets?

Blood Platelet Disorders↗