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  • 1
    Publication Date: 1993-09-01
    Description: Recent clinical data have shown that enzyme replacement therapy with macrophage-targeted glucocerebrosidase (GCR) can be effective in treating type 1 Gaucher disease. Sera from 262 patients, repeatedly infused with GCR, were assessed for the presence of antibodies to this therapeutic protein. Patient serum samples obtained at 3-month intervals were assessed by enzyme-linked immunosorbent assay and those with values greater than two standard deviations above the mean value obtained with a pool of normal human sera were further characterized by radioimmunoprecipitation. At the time of these analyses, the duration of patient treatment varied from 3 months to approximately 3 years. Of the 262 patients analyzed, 34 (12.9%) showed IgG antibodies, as confirmed by radioimmunoprecipitation. All patients who seroconverted did so within 1 year of treatment. The predominant antibody developed was the IgG1 subclass. Fourteen patients in the study experienced periodic symptoms suggestive of immediate hypersensitivity. Nine of these 14 patients had antibody to GCR as determined by radioimmunoprecipitation, whereas 5 patients were antibody negative. There was no evidence of the development of IgE antibodies in these 14 patients. The presence of GCR antibodies did not appear to effect efficacy of therapy in any of the patients treated to date.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 2
    Publication Date: 1996-06-01
    Description: Vasoactive intestinal peptide receptor I (VIPRI) expression was examined in megakaryocytes using reverse transcriptase-polymerase chain reaction (RT-PCR). VIPRI protein was characterized in platelet membranes using covalent crosslinking techniques. Human megakaryocytes were isolated from suspension cultures of cord blood and adult bone marrow mononuclear cells using a murine monoclonal antibody to human platelet glycoprotein IIB/IIIA (CD41) and immunomagnetic beads. RT-PCR primers were constructed for the VIP, VIPRI, and VIPRII genes as well as for megakaryocyte specific genes, c-mpl and platelet factor 4 (PF- 4). VIP, VIPRI, c-mpl, and PF-4 were coexpressed in megakaryocyte mRNA. Southern blot analysis confirmed the expression of VIPRI. 125I-VIP was covalently cross-linked to human platelet membranes using the homobifunctional reagent disuccinimidyl suberate, followed by polyacrylamide gel electrophoresis and autoradiography. A 125I-VIP- protein complex of Mr = 50,000 was identified. Labeling of the Mr = 50,000 component was completely abolished by unlabeled VIP, but not by peptide histidine methionine or growth hormone releasing factor, indicating specific binding of VIP to the platelet membranes. Taken together, these results suggest that VIP may have direct effects on megakaryocytopoiesis and support our earlier observations of VIP modulation of platelet aggregation.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 3
    Publication Date: 1993-09-01
    Description: Recent clinical data have shown that enzyme replacement therapy with macrophage-targeted glucocerebrosidase (GCR) can be effective in treating type 1 Gaucher disease. Sera from 262 patients, repeatedly infused with GCR, were assessed for the presence of antibodies to this therapeutic protein. Patient serum samples obtained at 3-month intervals were assessed by enzyme-linked immunosorbent assay and those with values greater than two standard deviations above the mean value obtained with a pool of normal human sera were further characterized by radioimmunoprecipitation. At the time of these analyses, the duration of patient treatment varied from 3 months to approximately 3 years. Of the 262 patients analyzed, 34 (12.9%) showed IgG antibodies, as confirmed by radioimmunoprecipitation. All patients who seroconverted did so within 1 year of treatment. The predominant antibody developed was the IgG1 subclass. Fourteen patients in the study experienced periodic symptoms suggestive of immediate hypersensitivity. Nine of these 14 patients had antibody to GCR as determined by radioimmunoprecipitation, whereas 5 patients were antibody negative. There was no evidence of the development of IgE antibodies in these 14 patients. The presence of GCR antibodies did not appear to effect efficacy of therapy in any of the patients treated to date.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
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