Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0272170 (SDS)
 50,377 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new type II variant form of von Willebrand's disease has been recognized in a mother and daughter who have bleeding manifestations typical of von Willebrand's disease. Laboratory findings include consistently prolonged bleeding times, with normal levels of factor VIII procoagulant and antigen, but decreased ristocetin cofactor activity. Electrophoresis in SDS 1.5% agarose gel and reaction with 125I-labeled anti-factor VIII-related antigen rabbit IgG, followed by autoradiography, revealed that both plasma and platelets lack the large multimers of factor VIII-related antigen. In 2.5% gel, the propositus plasma lacked the normal "triplet" pattern. In 3.0% gel, a 5-band pattern was observed in normal, type IIA, and type IIB plasma, whereas type IIC plasma revealed a 2-band pattern. The patient's plasma revealed a 4-band pattern distinctly different from normal or other type II variants. We suggest that this new variant be labeled type IID, until a more appropriate nomenclature is developed.
 ...
PMID:A new variant of dominant type II von Willebrand's disease with aberrant multimeric pattern of factor VIII-related antigen (type IID). 642 51

In seven patients with acquired von Willebrand's disease (AvWD) associated with lymphoproliferative disorders or benign monoclonal gammopathies, the platelet contents of von Willebrand factor antigen and ristocetin cofactor (vWF:Ag and vWF:RiCof, respectively) were normal. All the multimers of vWF:Ag could be seen in the 1.6% SDS-agarose gel electrophoresis patterns of plasma and platelet lysates. Infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) augmented plasma levels of vWF:Ag and vWF:RiCof of all patients and corrected prolonged bleeding times (BT). However, compared with patients with congenital vWD type I and comparable degrees of baseline abnormalities treated in the same way, vWF:Ag and vWF:RiCof were increased less and cleared more rapidly from plasma and the BT remained normal for a shorter period of time. These studies provide evidence that these AvWD patients have qualitatively normal vWF in plasma, but at lower concentrations, that vWF in platelets is normal both qualitatively and quantitatively, and that cellular vWF can be rapidly released into plasma by DDAVP to correct the hemostatic abnormalities. However, vWF is removed rapidly from plasma, making the correction more transient than in congenital vWD type I.
 ...
PMID:Studies of the pathophysiology of acquired von Willebrand's disease in seven patients with lymphoproliferative disorders or benign monoclonal gammopathies. 643 75

Monolayers of cultured human umbilical vein endothelial cells were exposed to 17 beta-estradiol and compared to control cultures with respect to levels of von Willebrand factor (vWF) released into the media after 3-5 days of incubation. The amount of functional vWF activity was assessed by ristocetin-induced platelet aggregation and by a radioreceptor platelet assay. vWF antigen was quantitated by immunoassay. The DNA content of each monolayer was determined fluorometrically and used as a measure of cell number. By all assays, vWF levels in the media from the estradiol-treated endothelial cells were reproducibly and significantly higher when compared with control values. The amount of vWF produced by the cultured endothelial cells showed a dose-response effect to the estradiol added to the media. The estradiol-treated cells produced approximately 1.3 +/- 0.30 micrograms vWF/ml/micrograms DNA at 2 ng estradiol/ml, compared with control cultures that produced 0.75 +/- 0.16 microgram vWF/ml/micrograms DNA (p less than 0.001). The estradiol-treated monolayers consistently contained slightly greater amounts of DNA than control cultures: 2.0 +/- 0.10 micrograms versus 1.7 +/- 0.12 micrograms DNA (p less than 0.001). By multivariant analysis, however, the differences in cell number could only account for less than or equal to 10% of the elevation in the level of vWF that occurred in response to estradiol. By SDS-agarose electrophoresis and radioimmunoblotting, the vWF within the cytosol of the endothelial cells was found to possess a multimeric pattern similar to that found for either purified plasma vWF or vWF released into media overlying endothelial cell cultures. Our studies indicate that estrogen directly stimulates endothelial cells to increase their rate of production of vWF and, in addition, causes a slight increase in endothelial cell replication. These data may bear on the observation that administration of estrogen to some women with von Willebrand's disease causes an increase in their functional levels of vWF.
 ...
PMID:Estrogen stimulates von Willebrand factor production by cultured endothelial cells. 660 57

Patterns of VIIIR:AG in the plasma and its fractions, cryoprecipitate and cryosupernatant, from various types of von Willebrand's disease (vWd) were observed by SDS 1.5% polyacrylamide gel electrophoresis - cross immunoelectrophoresis (SDS PAGE - CIE). VIIIR:AG in normal cryoprecipitate showed several precipitin peaks which correspond to molecular weights ranging from 8 X 10(5) to 1 X 10(7) daltons and are similar to those in normal plasma. Normal cryosupernatant VIIIR:AG gave smaller molecular weights from 8 X 10(5) to 2 X 10(6) daltons. VIIIR:AG in the plasma and cryoprecipitate from 2 patients with classical vWd gave low precipitin peaks with molecular weights in normal range. VIIIR:AG from 2 patients with subgroup A variant which showed fast anodal migration on the conventional CIE, presented 3 peaks with molecular weight of 8 X 10(5) to 3 X 10(6) which are similar to those in normal cryosupernatant. VIIIR:AG from 2 patients with subgroup B variant which showed normal migration on the CIE, gave normal patterns through all fractions.
 ...
PMID:Heterogeneity of molecular size of factor VIII/von Willebrand factor in von Willbrand's disease. 679 40

Type I von Willebrand's disease (vWd) is characterized by a concomitant decrease in plasma of von Willebrand factor antigen (vWf:Ag) and vWf ristocetin cofactor activity (vWf:RCoF), associated with the presence of all-size multimers. As a rule, there is no evidence of intrinsic abnormality in vWf. We describe a family with type I vWd with an abnormal plasma vWf multimer pattern. Analysis of plasma vWf multimeric structure by short-SDS-agarose gel electrophoresis showed an abnormal banding pattern for each vWf oligomer, which was organized as a doublet instead of the normal triplet. The electrophoretic mobility of each component appeared to be normal. Multimeric analysis on a long gel showed all the bands that were detectable in normal subjects, but unlike normals the fast moving satellite stained as the major component. The platelet vWf multimer pattern was normal. The infusion of DDAVP normalized vWf:Ag, vWf:RCoF and VIII:C, but not the abnormal multimer pattern observed on both short- and long-gel electrophoresis. The return of factor VIII/vWf complex to the baseline condition was more rapid than that observed in normal subjects or classic type I vWd patients. Analysis of the subunit fragments in the patients' plasma vWf demonstrated a relatively greater proportion, compared to the normal counterpart, of a 115(140)-kD fragment, which derives from the aminoterminal region of the mature molecule; in contrast, no intact subunit was detectable. These findings indicate a new, previously unreported, variant of type I vWd, which is characterized by plasma vWf oligomers organized as doublets, instead of triplets. The reduced post-DDAVP half-life, and the abnormal subunit fragments of vWf, suggest a molecule characterized by an increased susceptibility to proteolytic degradation. As a result, the decrease in circulating vWf levels may be due to an instability of the abnormal vWf, rather than, or in addition to, a decrease in its synthesis.
 ...
PMID:A new variant of von Willebrand's disease (type I Padua): doublet-organized plasma von Willebrand factor oligomers in the presence of all size multimers. 789 Feb 68

Diagnosis of von Willebrand's disease (vWD) requires quantitation of von Willebrand factor (vWF) in plasma plus qualitative assessment of the vWF multimers according to molecular size ranges. Characterization of vWF multimeric size distributions is typically done using sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE) followed by immunoblotting in the gel with radiolabeled antibody against vWF and autoradiographic exposure. We applied a western blot technique to vWF multimeric analysis. It included SDS-AGE, electroblotting onto a membrane, and chemiluminescent detection using rabbit anti-human vWF as primary antibody and goat anti-rabbit IgG as secondary antibody conjugated with horseradish peroxidase. Using this method, 18 to 20 vWF multimers were regularly resolved in normal plasma with exposure times of 2 to 4 sec compared to 4 hr or longer by autoradiography. Sensitivity of detection was at least 4-fold enhanced by chemiluminescence compared to radiolabel. Specificity of the assay was confirmed by analysis of plasma samples known to be deficient to different degrees in the larger vWF multimers. The chemiluminographic assay for vWF multimers is superior to the autoradiographic one because it is more sensitive, avoids use of radioactivity, and has shorter total assay time (under 2 days versus five radiolabel).
 ...
PMID:Chemiluminographic detection of von Willebrand factor multimeric composition. 827 55

This report describes studies investigating the use of a collagen binding assay to improve the laboratory monitoring of desmopressin (DDAVP) therapy in patients with von Willebrand's disease (vWD). We evaluated the response of seven patients with vWD (four type I, three type IIA) to DDAVP, administered using a standard protocol, by assessing levels of von Willebrand factor (vWF) and factor VIII, as well as performing skin bleeding times (SBT) prior to, and at sequential time points following, DDAVP administration. The study employed the following assays: von Willebrand factor antigen assay (vWF:Ag; determined by ELISA); a novel functionally based collagen binding assay (CBA; determined by ELISA); ristocetin cofactor assay (RCof; determined by platelet aggregometry); von Willebrand factor multimer analysis (using SDS-agarose gels); factor VIII coagulant (FVIIIC; determined by clotting assay); and factor VIII antigen (FVIIICAG; determined by ELISA). All patients showed an initial incremental increase in vWF/FVIII levels using all assays above, and some showed some correction in SBT. Although the absolute levels of vWF/FVIII antigen or activity varied between patients, the CBA was found to provide consistently the greatest proportional incremental increases (i.e., -fold) compared to baseline (pre-DDAVP) levels. Accordingly, we consistently observed an increase in the CBA to vWF:Ag ratio for all patients evaluated. This supplements previous findings that have suggested a unique ability of our CBA procedure to bind preferentially to higher molecular weight (i.e., more functionally active) forms of vWF. We therefore propose that the use of the above test combination (e.g., vWF:Ag plus CBA) may provide the basis for more accurate estimation of a patient's functional responsiveness to DDAVP therapy in future studies.
 ...
PMID:von Willebrand's disease: use of collagen binding assay provides potential improvement to laboratory monitoring of desmopressin (DDAVP) therapy. 829 90

This is the first case of variant von Willebrand disease (vWD) with defective binding of von Willebrand factor (vWF) to factor VIII (F.VIII) to be diagnosed in Japan. An 8-year-old Japanese girl, who had had recurrent episodes of subcutaneous hematomas, showed a prolonged A-PTT, low F.VIII (F.VIII:C 4 U/dl, FVIII:Ag 4 U/dl), and normal level of vWF (RCof 80 U/dl, vWF:Ag 60 U/dl). The patient's vWF-multimeric structure on SDS agarose gel electrophoresis was similar to that in normal subjects. A F.VIII binding assay was performed, as described by Nishino et al. (1989). F.VIII binding (y) of vWF was expressed as a function of the amount of immobilized vWF (x) on the wells of a polystyrene plate. Regression lines from normal subjects and the patient had a high correlation coefficient. F.VIII binding capacity was estimated by the slope of the regression lines. The slope for normal subjects showed y = 0.002 + 0.653x, while, in contrast, the slope for the patient showed y = 0.005 + 0.009x, indicating that the capacity of vWF from the patient to bind F.VIII was markedly decreased. Exons 18-20 of the vWF gene, covering the first 132 amino acids of mature vWF subunit from the patient, were sequenced, using the PCR amplification method. A point mutation C-->T at codon 816 in exon 19, predicting a substitution of Trp for Arg(53), was characterized; this was inherited by the patient from her mother.
 ...
PMID:Variant von Willebrand disease with defective binding to factor VIII: the first case from Japan. 849 94

A model for the in vivo clearance of normal and mutant forms of human von Willebrand factor (vWF) has been established using catheterized rats. vWF clearance rates in rat plasma were determined by quantitation of reduced vWF subunits on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and multimeric vWF was analyzed using nondenaturing SDS-agarose gels. Normal vWF derived from human umbilical vein endothelial cells displayed a biphasic pattern of clearance, with half times of 35 minutes (T 1/2 a; SD 15. min.) and 245 minutes (T 1/2 b; SD 76. min.); metabolic clearance rate = 0.65%/minute. High molecular weight multimers of vWF were cleared more rapidly than dimeric vWF. vWF containing the S1613P mutation found in some type 2A von Willebrand disease (vWD) patients was observed to undergo proteolysis in vivo resulting in a reduction of high molecular weight vWF and concomitant appearance of rapidly-migrating satellite species, although the overall clearance rate of vWF antigen was similar to wild type vWF. These results provide direct in vivo evidence that the S1613P mutation causes the characteristic type 2A vWD phenotype. Full-length recombinant vWF produced from transfected Chinese hamster ovary cells was cleared at a similar rate to endothelial cell-derived vWF, and recombinant vWF devoid of O-linked carbohydrates was cleared significantly faster. vWF devoid of sulfate was cleared at a similar rate as wild type vWF, indicating the sulfate moiety of vWF does not regulate in vivo clearance. This animal model should prove useful in subsequent in vivo analysis of additional forms of vWD and in the development of protease inhibitor therapy for 2A vWD.
 ...
PMID:Clearance of normal and type 2A von Willebrand factor in the rat. 878 25

In order to provide patients with von Willebrand disease a factor VIII (FVIII)/von Willebrand factor (vWF) concentrate of reproducible quality, an SDS-agarose gel electrophoresis method has been established to determine the content of the high molecular weight multimers (band 11 and higher) of vWF. This method has been used to characterize the content of high molecular weight vWF multimers in Humate P/Haemate P, a commercial FVIII/vWF concentrate. The average content of high molecular weight vWF multimers of 47 batches of Humate P/Haemate P has been determined to be 84.1% of the corresponding bands in normal human plasma. Use of this multimer analysis method for the characterization of five further commercial products revealed clear differences with respect to the high molecular weight vWF multimer content. Furthermore, there is a linear correlation (r2 = 0.73) between the content of high molecular weight vWF multimers and the specific activity of vWF (determined as vWF:RCoF/vWF:Ag). The method described here for analysis of the content of high molecular weight vWF multimers is a reliable and reproducible method to characterize this class of factor concentrates with respect to vWF multimer composition.
 ...
PMID:Characterization of factor VIII/von Willebrand factor concentrates using a modified method of von Willebrand factor multimer analysis. 1002 15


<< Previous 1 2 3 4 5 Next >>