PubMed Health⌕ Search

Biomedical subjects

T Wun

Publications and source records attributed to T Wun.

27 records · Page 2Linked to original sources
PubMed1995

Desmopressin stimulates the expression of P-selectin on human platelets in vitro.

Desmopressin (1-desamino-8-D-arginine vasopressin (DDAVP)) is a synthetic analog of arginine vasopressin (AVP) and is useful in the treatment of some bleeding disorders. The mechanism of improved hemostasis in patients with platelet dysfunction is uncertain. Platelet-rich plasma samples from 35 normal subjects were incubated with serial dilutions of DDAVP, AVP, and adenosine diphosphate. The expression of the platelet activation-dependent antigen CD62 (P-selectin) was measured by fluorescent-labeled monoclonal antibody and flow cytometry. DDAVP at concentrations of 1.0 to 1000 nmol/L stimulated significant expression of CD62 on normal platelets in vitro. At a pharmacologic concentration of DDAVP (1 nmol/L), 14.1% (0.6% to 45.4%) (median and range) of platelets expressed CD62. There was a strong correlation between DDAVP-induced and AVP-induced CD62 expression (rs = 0.62, p = 0.0008) but not between DDAVP-induced and ADP-induced expression, suggesting a V1 receptor-mediated mechanism. Preincubation of platelets with a vasopressin V1 receptor antagonist completely inhibited CD62 expression in response to DDAVP. We conclude that DDAVP directly activates platelets by interaction with the platelet V1 receptor in vitro. This finding may partially explain in vivo effects of DDAVP on hemostasis.

Adenosine Diphosphate↗
PubMed1994

Prolonged circulation of activated platelets following plasmapheresis.

The extent and duration of in vivo platelet activation were determined in 12 volunteer donors undergoing automated plasmapheresis. Expression of P-selectin, activated GpIIb/IIIa, and platelet microparticle formation were measured by flow cytometry on peripheral blood samples obtained immediately before and after plasmapheresis and at 24 hour intervals thereafter for up to 3 days. Although no adverse effects were noted in any donor, immediately after apheresis 3-87% of circulating platelets expressed P-selectin; by 48 hours, 0.5-50% expressed P-selectin; and by 72 hours, all donors studied had fewer than 5% P-selectin expression on circulating platelets. Results were similar for the expression of the activated conformation of GpIIb/IIIa. There was a positive correlation with in vitro P-selectin expression in response to ADP in the pre-apheresis sample and the number of platelet microparticles detected in the donor following plasmapheresis. In addition, the percent expression of P-selectin and activated GpIIb/IIIa in response to ADP was reproducible in each individual studied on five separate occasions (CV < or = 8%). Platelets activated during plasmapheresis using an automated device may circulate for at least 48 hours, and pre-plasmapheresis response of platelets to the agonist ADP correlated with platelet microparticle formation post-plasmapheresis.

Adenosine Diphosphate↗
PubMed1992

Clonal remission in aplastic anemia after treatment with antithymocyte globulin.

Aplastic anemia includes a group of disorders characterized by peripheral blood pancytopenia and marrow hypocellularity. The current report describes a patient who is an apparent constitutional mosaic and presented with marrow aplasia. Using cytogenetic analysis of bone marrow, skin, and peripheral T lymphocytes, we demonstrated the clonal nature of this patient's aplastic marrow, and, in addition, identify clonal evolution. The patient was treated with antithymocyte globulin (ATG) and achieved a complete remission, with disappearance of an abnormal evolved clone. This case illustrates that clonal cytogenetic abnormalities do not preclude a response to ATG and that aplastic anemia may be a nonmalignant clonal disorder with clonal evolution.

Aged↗
PubMedDate not supplied

Detection of plasmapheresis-induced platelet activation using monoclonal antibodies.

Twelve volunteer plasma donors were studied so as to determine the extent and duration of in vivo platelet activation caused by automated plasmapheresis. Samples obtained immediately before and after donation were mixed with murine monoclonal antibodies PAC-1 and S12, which bind specifically to activated platelets. Antibody binding on platelets was quantitated by flow cytometry. The change in the mean fluorescence intensity (MFI) (MFI after donation minus MFI before donation) was 61 +/- 23 (confidence interval [CI], 48-75) for PAC-1 and 56 +/- 64 (CI, 19-92) for S12 in plasmapheresis donors, as compared to 0.3 +/- 0.8 (PAC-1; CI, -0.2-0.8) and 0.3 +/- 0.9 (S12: CI, -0.3-0.9) in whole blood donors (p less than 0.05). Additional studies showed circulating activated platelets up to 48 hours after plasmapheresis. In contrast to other data, significant platelet activation was demonstrated following plasmapheresis on an automated machine. None of the donors had clinical complications. Nevertheless, it may be appropriate to delay subsequent plasmapheresis and platelet procurement from such donors until evidence of platelet activation has disappeared.

Antibodies, Monoclonal↗
PubMedDate not supplied

Removal by white cell-reduction filters of activated platelets expressing CD62.

White cell (WBC)-reduction filters that remove more than 99 percent of the WBCs from platelet concentrates are rapidly being introduced into routine use. Using activation-dependent monoclonal antibodies and flow cytometry, platelet activation was evaluated before and after WBC reduction in 10 platelet concentrates prepared manually from whole blood obtained from five male and five female regular volunteer blood donors. In general no significant increases were found in platelet activation markers after WBC reduction using filters. However, if platelets were activated during preparation, increased numbers of platelets were found expressing the activation marker CD62, and this correlated with the decrease in the platelet count after WBC reduction. These observations may explain increased platelet loss following WBC reduction in some platelet components.

Antibodies, Monoclonal↗
PubMedDate not supplied

A phase I study of 90Y-2IT-BAD-Lym-1 in patients with non-Hodgkin's lymphoma.

BACKGROUND: Prior clinical trials proved that all histologic grades of chemotherapy-resistant B-cell non-Hodgkin's lymphoma (NHL) could respond to radio-immunotherapy (RIT) with 131I-Lym-1 and 67Cu-2IT-BAT-Lym-1. This Phase I study was conducted to determine the safety and maximum tolerated dose (MTD) of 90Y-2IT-BAD-Lym-1. METHODS: Lym-1 is a mouse monoclonal antibody that preferentially targets malignant B-lymphocytes. 90Y has beta emissions suitable for therapy but no gamma emissions, therefore, 111In-2IT-BAD-Lym-1 is used for imaging. The macrocyclic chelator, DOTA, bound 90Y tightly to form a stable drug. Patients with chemotherapy-resistant NHL received 90Y-2IT-BAD-Lym-1 at administered doses of: 0.185, 0.278, or 0.370 GBq/m2. RESULTS: Myelotoxicity, especially thrombocytopenia, was dose-limiting. No significant non-hematologic toxicity occurred. Human anti-mouse antibody (HAMA) developed in 3/8 patients. The mean radiation dose to the 33 imaged tumors was 7.0 Gy/GBq. Lung, kidney and liver received mean radiation doses of 1.3, 2.4, and 6.4 Gy/GBq, respectively from 90Y-2IT-BAD-Lym-1. The tumor: body and tumor:bone marrow (by imaging) ratios were 16.4:1 and 5.8:1, respectively. In this Phase I study, 5/8 patients that failed prior chemotherapy had a partial response or stabilization of NHL after RIT. CONCLUSION: The safety and toxicity of 90Y-2IT-BAD-Lym-1 were determined and the MTD was 0.370 GBq/m2, a dose used in 4 patients. 90Y-2IT-BAD-Lym-1 may be useful for future clinical trials because 90Y is readily available and can deliver potent beta emissions to NHL. Bone marrow support however, will be required for further dose escalation.

Adult↗