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S Murphy

Publications and source records attributed to S Murphy.

At least 433 records · Page 24Linked to original sources
PubMed1983

Exposure of platelet fibrinogen-binding sites by collagen, arachidonic acid, and ADP: inhibition by a monoclonal antibody to the glycoprotein IIb-IIIa complex.

Following stimulation with adenosine diphosphate (ADP), collagen, or arachidonic acid, unstirred human platelet suspensions bind 125I-fibrinogen in a reaction that reaches completion within 30 min. Scatchard analysis of these binding data reveals two sets of binding sites with all 3 agents: a high affinity site (Kd 0.029-0.045 microM) binding 1000-1600 fibrinogen molecules per platelet, and a lower affinity site (Kd 1.2-2.0 microM) binding 46,000-76,000 fibrinogen molecules per platelet. At a concentration of apyrase that inhibited ADP-induced fibrinogen binding by greater than 85%, fibrinogen binding induced by collagen and arachidonic acid was only partially affected. This suggests that fibrinogen binding induced by collagen or arachidonic acid does not require released ADP. We isolated a monoclonal antibody, B59.2, which precipitated the glycoprotein IIb-IIIa complex from solubilized platelet membranes. Binding of labeled antibody to platelets before or after exposure to ADP, collagen, or arachidonic acid showed a single class of approximately 22,000 binding sites with Kd 0.019 microM. Binding of B59.2 was complete within 1 min and was not inhibited by EDTA. Preincubation of platelet suspensions with a 2.1 microM concentration of B59.2 caused inhibition of secretion and aggregation, but not of thromboxane-B2 synthesis, in response to 1 microgram/ml collagen, 40 microM arachidonic acid, or 4 microM ADP, concentrations of aggregating agents that produced complete aggregation and secretion in the absence of B59.2. At this concentration of B59.2, fibrinogen binding to stimulated platelets was inhibited by approximately 45%-55%. These data demonstrate that collagen and arachidonic acid can expose fibrinogen binding sites independently of released ADP; and that the glycoprotein IIb-IIIa complex is involved in secretion, aggregation, and fibrinogen binding, but not in thromboxane synthesis occurring in response to collagen, arachidonic acid, or ADP.

Adenosine Diphosphate↗
PubMed1983

Exposure of fibrinogen receptors on fresh and stored platelets by ADP and epinephrine as single agents and as a pair.

Platelet concentrates stored at 22 degrees C have a marked decrease in their aggregation response to adenosine diphosphate (ADP) or epinephrine but a normal response to these agents when used as a pair. Since platelet stimulation involves exposure of receptors for fibrinogen, we studied fibrinogen binding to platelets from fresh and stored concentrates. Following stimulation with 10 microM ADP or 20 microM epinephrine, platelet suspensions from fresh concentrates bound 125I-fibrinogen in a reaction that reached completion within 30 min. Significantly less binding occurred in suspensions from platelet concentrates that had been stored for 5 days at 22 degrees C. When stimulated by ADP and epinephrine as a pair (2 microM each), binding of fibrinogen to platelets was complete within 10-15 min and was not significantly decreased in suspensions from stored concentrates. We also investigated the effect of storage on the glycoprotein IIb-IIa complex, thought to be a specific receptor for fibrinogen on the platelet surface. Binding of a monoclonal antibody specific for this complex (B59.2) to platelet suspensions was unaffected by 5 days of storage. Furthermore, B59.2 inhibited aggregation, secretion, and fibrinogen binding of fresh and stored platelets stimulated with the pair of agents just as it did with single agents. We conclude that storage for 5 days at 22 degrees C impairs the exposure of fibrinogen receptors on platelets in response to ADP or epinephrine when used as single agents, without affecting the glycoprotein IIb-IIIa complex quantitatively. The function of the receptor is normal in response to the pair of agents.

Adenosine Diphosphate↗
PubMed1983

Lung defenses against infection: a clinical correlation.

The current state of knowledge of lung defenses has been reviewed. First, mechanical factors such as aerodynamic filtration and mucociliary transport were considered. Then, in general terms, the contributions of alveolar macrophages, neutrophils, lymphocytes, and immunoglobulins, and the roles of complement, antiproteases, lysozyme, and fibronectin were examined. Interactions between these components may regulate their effect. Finally, the responses to five specific microorganisms were reviewed to illustrate different aspects of the lung's defenses. Streptococcus pneumoniae was selected as a representative extracellular bacterial pathogen, Mycobacterium tuberculosis as an intracellular bacterial pathogen, Mycoplasma pneumoniae because it elicits significant humoral and cell-mediated immunity, respiratory syncytial virus as an example of a local viral pathogen, and measles as a viral pathogen that causes generalized disease. It was shown that these responses may not always be beneficial for the host. For each of the five infections, recommendations for improving the outcome were made.

Cilia↗
PubMed1983

Monitoring the entry of new platelets into the circulation after ingestion of aspirin.

There have been reports of a 24-48-hr delay in the recovery of platelet cyclooxygenase activity and platelet function after the ingestion of aspirin. However, these studies employed a single aggregating agent to stimulate enzymatic or functional activity. We investigated the effects of some pairs of aggregating agents on 14 platelet-rich plasmas (PRP) from normal subjects 2 and 4 hr after ingestion of 650 mg aspirin and daily up to 72 hr. We studied platelet aggregation and secretion with a lumiaggregometer and thromboxane-B2 formation by radioimmunoassay. Aggregation and secretion occurred as early as 4 hr after aspirin ingestion in response to combinations of arachidonic acid with epinephrine, collagen, or adenosine diphosphate (ADP). Thromboxane formation was detected as early as 4 hr after ingestion of aspirin in response to 1 mM arachidonic acid in combination with 1 microgram/ml collagen. Up to 72 hr, there was a linear return of thromboxane formation stimulated by this combination, reflecting the entry of new platelets into the circulation. In vitro experiments with mixtures of aspirin-free and aspirin-treated platelets showed that the combination of collagen and arachidonic acid (AA) could produce full aggregation and secretion when only 2.5% of aspirin-free platelets were present. Use of the combination of collagen plus AA demonstrates the early entry into the circulation of platelets originating from megakaryocytes whose cyclooxygenase has not been completely acetylated.

Adenosine Triphosphate↗
PubMed1983

The role of ADP secretion and thromboxane synthesis in factor VIII binding to platelets.

Following stimulation with arachidonic acid, collagen, U-46619 (a stable analogue of prostaglandin endoperoxide/thromboxane-A2), thrombin, or adenosine diphosphate (ADP), unstirred human platelet suspensions bound labeled factor VIII in a reaction that reached equilibrium within 10 min. Apyrase inhibited binding induced by arachidonic acid, collagen, U-46619, and thrombin by less than 40%, but inhibited ADP-induced binding by 95%. Binding to aspirin-treated platelets was normal in response to U-46619, reduced by 60%-70% in response to ADP, collagen, and thrombin, and absent in response to arachidonic acid. Binding in response to U-46619 was not altered by the combination of apyrase and aspirin. Binding of factor VIII was decreased by 90% when 10 mM EDTA was added before each agonist, but it was inhibited less than 30% when EDTA was added following platelet stimulation. We conclude that arachidonic acid, collagen, and thrombin can expose binding sites for factor VIII independently of released ADP; that Ca++ is required for activation but probably not for binding of factor VIII to platelets; and that platelet thromboxane synthesis plays a major role in the binding of factor VIII to platelets induced by thrombin, ADP, or collagen.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1983

Association of the human type C retrovirus with a subset of adult T-cell cancers.

To determine whether the human T-cell lymphoma-leukemia virus (HTLV) is associated with particular cancers, patient sera were surveyed for HTLV-specific antibodies. An association was seen with aggressive cancers of mature T-cells, specifically Japanese adult T-cell leukemia (ATL) and T-cell lymphosarcoma cell leukemia (TLCL), a similar cancer of Caribbean blacks. Ninety to 100% of these patients possessed HTLV-specific antibody. Forty-seven and 20% of relatives of ATL and TLCL patients, respectively, and 12 and 4% of healthy donors from ATL and TLCL endemic areas were also antibody positive. Visceral organ involvement, hypercalcemia, and skin manifestation, features of ATL and TLCL, were often seen in other antibody-positive patients. Childhood cancers, most cutaneous T-cell and all non-T-cell leukemias and lymphomas, myeloid leukemias, Hodgkin's disease, and solid tumors were not associated with HTLV. Healthy United States donors and European patients with non-malignant diseases were antibody negative. HTLV is thus associated with a subtype of adult T-cell leukemia-lymphoma, clustered in viral endemic areas, with apparent racial and geographic predilection.

Adult↗
PubMed1983

Platelet storage at 22 degrees C for transfusion: interrelationship of platelet density and size, medium pH, and viability after in vivo infusion.

Previous studies have suggested that there are two characteristic storage lesions that develop during storage of PC at 22 degrees C with constant agitation in containers constructed from PVC plastic. One occurs only in PC with high platelet count in which there is a fall in pH due to hypoxic conditions within the container. This storage lesion is characterized by an increase in apparent mean volume as determined by Coulter Counter and a change in platelet shape from disc to sphere. The other is observed in PC with low platelet counts; in these, a major pH fall does not occur. Under these conditions, there is a decrease in the apparent mean volume and an increase in the dispersion of the size distribution determined by Coulter Counter. The cause of this storage lesion is uncertain. However, it appears to be more pronounced with some forms of agitation than with others. In the current studies, we have attempted to clarify further the nature of these two storage lesions. We now show that during fall in pH of PC to levels below 6.8, the increase in apparent platelet volume corresponds well with a decrease in platelet density and refractive index, both consistent with cellular swelling due to influx of extracellular fluid. We were previously unable to determine whether this lesion was due to pH fall per se or to the associated hypoxic conditions. In the current study, platelets stored under a nitrogen atmosphere for as long as 7 days show no swelling or shape change when the pH is kept above 6.8, suggesting that the damage is due to pH fall per se. In previous studies of the second storage lesion, which occurs without pH fall, we have found that the increase of the dispersion of the Coulter volume distribution correlates with loss of in vivo viability measured as percent recovery after labelling with chromium-51. In this study, we show that the increase in dispersion results from the presence of a population of abnormally light platelets. Since this light population labels normally with chromium-51, we hypothesize that it contains the cells which fail to circulate after in vivo infusion. In three infusions of thrombocytopenic patients, we support this hypothesis by showing that the abnormal light population does not circulate in vivo and that the dispersion of the apparent volume distribution of the circulating cells is normal.

Blood Platelets↗
PubMed1982

Secretion defect in platelets stored at 4 degrees C.

To understand the functional changes induced by storage, we have examined the adenine nucleotides of platelets stored for 72 hr at 22 degrees C and 4 degrees C. Ten platelet concentrates (PC) were stored at each temperature with five in each group having a final volume of 50 ml and 30 ml. The total ATP and ADP content of platelets decreased following storage in all 4 groups of PC, with the decrease being greater in the PC stored at 22 degrees C than those at 4 degrees C. The mean thrombin secretable ATP + ADP content of platelets from PC stored at 22 degrees C and 4 degrees C were 29.7% and 19.7% of the total content, respectively (p less than 0.001). Thus, cold stored platelets have a higher total content of ATP + ADP but secrete distinctly lesser amounts than 22 degrees C stored platelets. Labeling of the metabolic pool adenylates with 14C-adenine revealed a greater decrease in the adenylate energy charge of the platelets stored at 4 degrees C. The secretion defect demonstrated in cold stored platelets may be related to the inability of these platelets to maintain ATP homeostasis.

Adenosine Diphosphate↗
PubMed1982

Nasopharyngeal carcinoma in American Children: Epstein-Barr virus-specific antibody titers and prognosis.

Seven American juvenile patients with undifferentiated or nonkeratinizing nasopharyngeal carcinoma (NPC) were examined serially for Epstein-Barr virus (EBV)-specific antibody spectra and titers in sera. At diagnosis, all showed antibody patterns characteristic of NPC: i.e., high titers of IgG antibodies to viral capsid antigen (VCA) and to the diffuse (D) component of the early antigen complex. Six patients had IgA antibodies to VCA, and four to the D component. In the patients who responded to therapy with complete and maintained remissions, the IgG antibodies to D and the IgA antibodies to VCA and D decreased to undetectable levels within 12 to 30 months. By contrast, of the four patients who responded only transiently to therapy, three showed substantial increases and one continuously high titers of IgG anti-D and IgA anti-VCA. The increases in antibody titers preceded clinical recognition of recurrent tumors by 1 to 6 months. Three of these patients have died and the fourth is alive with disease. These data indicate that American juvenile NPC does not differ from the adult disease observed anywhere in the World. They reaffirm the potential usefulness of EBV-specific serology in the diagnosis and prognosis of NPC and the monitoring of patients following therapy.

Adolescent↗
PubMed1982

Indications for platelet transfusion in children with acute leukemia.

In an attempt ot determine the indications for platelet transfusion in thrombocytopenic patients, we randomized 56 children with acute leukemia to one of two regimens of platelet transfusion. The prophylactic group received platelets when the platelet count fell below 20,000 per mm3 irrespective of clinical events. The therapeutic group was transfused only when significant bleeding occurred and not for thrombocytopenia alone. The time to first bleeding episode was significantly longer and the number of bleeding episodes were significantly reduced in the prophylactic group. The survival curves of the two groups could not be distinguished from each other. Prior to the last month of life, the total number of days on which bleeding was present was significantly reduced by prophylactic therapy. However, in the terminal phase (last month of life), the duration of bleeding episodes was significantly longer in the prophylactic group. This may have been due to a higher incidence of immunologic refractoriness to platelet transfusion. Because of this terminal bleeding, comparison of the two groups for total number of days on which bleeding was present did not show a significant difference over the entire study period.

Actuarial Analysis↗