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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

Use of the activated partial thromboplastin time for heparin monitoring.

The objectives of the present study were to evaluate the relationship between heparin concentration and activated partial thromboplastin time (aPTT) results, define a heparin concentration-derived therapeutic range for each aPTT instrument, compare aPTT- and heparin concentration-guided dosage adjustment decisions, and compare laboratory- and bedside aPTT-guided decisions. In phase 1, 102 blood samples were analyzed for bedside and laboratory aPTTs and heparin concentration (used to establish aPTT therapeutic range). In phase 2, 100 samples were analyzed in the same manner. Correlations for aPTT compared with heparin ranged from 0.36 to 0.82. Dosage adjustment decisions guided by the aPTT agreed with those based on heparin concentration 63% to 80% of the time. Laboratory and bedside aPTT dosage adjustment decisions agreed 59% to 68% of the time. The correlation of aPTT with heparin concentration and agreement between aPTT- and heparin-guided decisions vary with the aPTT instrument. Decisions guided by laboratory aPTT results often disagree with decisions guided by bedside aPTT results.

Aged↗

Hepatosplenic gamma/delta T-cell lymphoma in immunocompromised patients. Report of two cases and review of literature.

We describe 2 male patients in whom hepatosplenic gamma/delta T-cell lymphoma (HSTL) developed 6 and 10 years after renal transplantation. The onset was abrupt with systemic symptoms, cytopenia, and hepatosplenomegaly. The histologic examination of the spleen (case 1), liver, and bone marrow revealed sinusoidal infiltrates of markedly abnormal lymphocytes. The neoplastic cells in these cases were CD2+, CD3+, CD4-, CD5-, CD7+, CD8+, CD16+, CD56+, beta F1-negative, and TIA-1-negative. Both cases displayed clonal rearrangement of the T-cell receptor (TCR) delta gene and the TCR beta gene. The spleen in case 1 was positive for Epstein-Barr virus genome and showed TCR-gamma gene rearrangement by polymerase chain reaction. Isochromosome 7 [i(7)(q10)] was found in each case. Both patients died within 4 months of diagnosis. HSTL has been reported in only 5 renal transplant recipients. HSTL may be relatively more frequent in immunocompromised patients compared with the general population.

Adult↗

Combined factor V Leiden and prothrombin genotyping in patients presenting with thromboembolic episodes.

BACKGROUND: Several genetic defects are associated with increased risk of venous thrombosis. The factor V Leiden (FVL) and prothrombin G20210A mutations are the most frequent causes of inherited thrombophilia. OBJECTIVES: To evaluate combined genotyping for these 2 mutations in patients presenting with thromboembolic episodes and to correlate genotypic findings with clinical characteristics. RESULTS: Blood specimens were collected from 401 patients presenting with thromboembolic disease between January 1998 and September 1998, and genotyping for both FVL and prothrombin mutations was performed. Thirty-two patients (8%) were heterozygous for FVL, 4 (1%) were homozygous for FVL, and 20 (5%) were heterozygous for the prothrombin mutation. Two cases (0.5%) were identified with combined FVL and prothrombin mutations. The most common clinical presentation was lower-extremity deep vein thrombosis with or without pulmonary embolism. Arterial events were rare. The thromboembolic episodes were often precipitated by additional risk factors. Recurrent disease was found in 73.9% of FVL carriers and 52.9% of prothrombin mutation carriers; 52% of the patients with FVL and 50% of prothrombin mutation carriers had a first thrombotic episode before age 45 years. The 2 cases with combined genetic defects demonstrate amplified thrombotic risk. In the first case this was effected in thrombosis at a young age, and recurrence of thrombotic events even in the absence of precipitating factors. A complex interplay between genetic and additional risk factors was seen in the second case. CONCLUSIONS: Identification of both FVL and prothrombin mutations is important in the overall assessment and management of patients with thrombophilia. Detection of these mutations can identify patients at high risk and help evaluate the interaction of genetic and acquired risk factors.

Adult↗

Different heparin lots: Does it matter?

OBJECTIVE: To assess the impact of heparin lot on the correlation between heparin concentration and activated partial thromboplastin time (aPTT), the aPTT therapeutic range, and the heparin level. DESIGN: Retrospective analysis of data from 2 previous studies. SETTING: Teaching institution with 929 beds. PATIENTS: Ninety-five patients receiving heparin with 5 different lots (study 1) and 35 patients receiving heparin with 3 different lots (study 2). MAIN OUTCOME MEASURES: Laboratory-based aPTT and heparin level by anti-factor Xa analysis. Standard heparin curves were created for each lot. Each patient's heparin level was determined off each standard curve. RESULTS: Correlations between heparin concentration and aPTT ranged from 0.87 to 0.89 (study 1) and 0.86 to 0.87 (study 2). Slopes of regression lines were not significantly different. Therapeutic ranges generated from lot-specific heparin levels were similar. Average bias in heparin levels from varying lots ranged from 0.005 to 0.036 units/mL. CONCLUSIONS: The recommendation to reevaluate the aPTT therapeutic range with each new lot of heparin requires further evaluation.

Analysis of Variance↗

Myelodysplastic syndrome at a large tertiary care community hospital: analysis according to the international prognostic scoring system.

The outcome of patients diagnosed myelodysplastic syndromes (MDS) between 1990 and 1997 from William Beaumont Hospital (WBH) was analyzed according to the International Prognostic Scoring System (IPSS) risk categorization. A retrospective study of 195 MDS patients wa s performed. Seventy-nine patients with MDS, in whom a karyotype was obtained and with an adequate follow-up were included in the final analysis. Cases of proliferative CMML (WBC > 12x10(9)/l) were excluded from the study. The overall median survival was 3.1 years, and median survival stratified by IPSS was 3.4, 4.1 and 0.5 years for the INT-1, INT-2 and high risk group and not yet reached for the low risk group. The overall survival by IPSS subcategorization were 6.88, 5.29, 5.30 and 2.12 years for the low, INT-1, INT-2, and high risk groups respectively. Cytogenetics were significant in predicting the overall survival. The IPSS score stratified patients into risk categories for development of AML. The risk of development into AML was 8, 8, 33 and 54% for the low, INT-1, INT-2 and high risk groups, respectively. We conclude that IPSS score can be useful in predicting survival and AML evolution in some MDS patients.

Acute Disease↗

Acute promyelocytic leukemia. From morphology to molecular lesions.

Acute promyelocytic leukemia is a unique subtype of acute myelogenous leukemia characterized by distinct morphologic, cytogenetic, and clinical characteristics. The t(15;17) translocation, which is a hallmark of this disease, results in a transcriptionally active fusion gene-derived from the PML gene from chromosome 15 and the retinoic acid receptor alpha (RARa) gene from chromosome 17. The PML/RARa protein product is responsible for the leukemic phenotype in these patients, but is also able to respond to pharmacologic levels of retinoic acid and induce cell differentiation. Treatment of this leukemia by retinoic acid represents the first example of gene-directed differentiation therapy for acute leukemia and has lead to greater understanding of the pathogenesis of this disease at the molecular level.

Chromosome Aberrations↗

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↗

Lymphoma of the breast. A clinicopathologic study of primary and secondary cases.

BACKGROUND: Primary lymphomas of the breast are rare, accounting for 1.7% to 2.2% of extranodal lymphomas and 0.38% to 0.7% of all non-Hodgkin lymphomas. Although secondary breast lymphomas are also rare, they represent the largest group of metastatic tumors of the breast. OBJECTIVES: To investigate the clinicopathologic and immunophenotypic characteristics of breast lymphomas, the relative frequency of primary and secondary mammary lymphomas, and in selected cases, the role of gene rearrangement analysis in diagnosis and staging of these lymphomas. RESULTS: We conducted a retrospective review of 22 cases of breast lymphoma diagnosed at William Beaumont Hospital, Royal Oak, Mich, during a 30-year period (1963-1994). Eleven of the 22 cases fulfilled the criteria for primary breast lymphoma; these cases represented 0.6% of all non-Hodgkin lymphomas seen in our hospital. Of the 11 cases, 5 were diffuse large B-cell lymphomas, 2 were follicle center lymphomas, 2 were marginal zone B-cell lymphomas (mucosa-associated lymphoid tissue type), 1 was a lymphoplasmacytoid lymphoma, and 1 was a peripheral B-cell neoplasm, unclassified. Using a panel of immunohistochemical stains (CD45RO, CD45RA, CD43, CD3, CD20, CD30, CD68, and HLA-DR), 8 cases demonstrated unequivocal B-cell phenotype and 3 cases had equivocal or weak staining patterns for B-cell markers. We identified no cases of T-cell lymphoma. Of 7 cases that had bone marrow biopsies for staging, 3 were positive morphologically for bone marrow involvement. Molecular analysis of B- and T-cell gene rearrangement was used to exclude bone marrow involvement in one case with bone marrow lymphoid aggregates and to confirm negativity in a case that was morphologically negative. Of the 11 secondary breast lymphomas, 5 were diffuse large B-cell lymphomas; 1 was diffuse large B-cell, primary mediastinal subtype; and 5 were follicle center lymphomas. CONCLUSIONS: Breast lymphomas represented 1.2% of all non-Hodgkin lymphomas in this study; the frequency of primary and secondary cases was equal. In both groups, right breast lesions were predominant, and the most frequent morphologic type was diffuse large B-cell lymphoma. Gene rearrangement analysis is helpful in selected cases to rule out bone marrow involvement, especially in older patients, in whom lymphoid aggregates are common.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗