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Biomedical subjects

R Bader

Publications and source records attributed to R Bader.

At least 73 records · Page 4Linked to original sources
PubMed1985

Heterogeneity of type I von Willebrand disease: evidence for a subgroup with an abnormal von Willebrand factor.

Type I von Willebrand disease (vWD) is characterized by equally low plasma concentrations of von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor (RiCof) and by the presence of all vWF multimers in sodium dodecyl sulfate (SDS)-agarose gel electrophoresis. For 17 patients (13 kindreds) diagnosed with these criteria, we have studied the platelet contents of vWF:Ag and RiCof and the changes of these in plasma after DDAVP infusion. Platelet vWF:Ag and RiCof were normal in four kindreds (called "platelet normal" subgroup); following 1-deamino-8-D-arginine vasopressin; plasma vWF:Ag, RiCof and the bleeding time (BT) became normal. In six kindreds, platelet vWF:Ag and RiCof were equally low (platelet low); after DDAVP, plasma vWF:Ag and RiCof remained low, and the BT was prolonged. In three additional kindreds, platelets contained normal concentrations of vWF:Ag, but RiCof was very low (platelet discordant); even though a complete set of multimers was found in plasma and platelets, there was a relatively small amount of large multimers. After DDAVP, plasma vWF:Ag became normal, but RiCof remained low and the BT was very prolonged. These findings demonstrated that there can be an abnormal vWF (RiCof less than vWF:Ag) even in type I vWD, coexisting with a complete set of vWF multimers (platelet discordant); that the abnormal vWF can be shown more clearly in platelets than in plasma or else in plasma after DDAVP infusion; and that DDAVP normalizes the BT only in those patients with normal platelet levels of both vWF:Ag and RiCof (platelet normal).

Autoradiography↗
PubMed1984

Studies of the pathophysiology of acquired von Willebrand's disease in seven patients with lymphoproliferative disorders or benign monoclonal gammopathies.

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.

Adult↗
PubMed1983

Platelets have more than one binding site for von Willebrand factor.

The binding of 125I-von Willebrand factor (125I-vWF) to platelets stimulated by thrombin, ADP, and a combination of ADP + epinephrine (EPI) is specific, saturable, and reversible. Active platelet metabolism and divalent cations are required for binding induced by these stimuli, but not by ristocetin, suggesting the existence of different mechanisms involved in the vWF-platelet interaction. A monoclonal antibody directed against an epitope of membrane glycoprotein (GP) Ib had no effect on the binding of 125I-vWF to normal platelets stimulated by thrombin or a combination of ADP + EPI, but completely blocked ristocetin-induced binding. Binding induced by thrombin to GPIb-blocked platelets was specific. Moreover, thrombin-induced binding of 125I-vWF was increased, rather than decreased, in two patients with the Bernard-Soulier syndrome whose platelets lacked GPIb. Conversely, monoclonal antibodies directed against the GPIIb/IIIa complex had no effect on ristocetin-induced binding of 125I-v-WF to normal platelets, but blocked thrombin- and ADP + EPI-induced binding. To exclude effects mediated by the platelet Fc receptor, a monoclonal IgG directed against an epitope present on human B cells and monocytes, but not expressed on resting or stimulated platelets, was used. It did not affect 125I-vWF binding induced by any of the stimuli. These studies show that platelets have more than one binding site for vWF, and that they may be exposed by different stimuli.

Adenosine Diphosphate↗
PubMed1982

Glanzmann thrombasthenia: deficient binding of von Willebrand factor to thrombin-stimulated platelets.

Glanzmann thrombasthenia is an inherited bleeding disorder characterized by the failure of platelets to aggregate in response to almost all stimuli. However, thrombasthenic platelets will aggregate with bovine and porcine von Willebrand factor (vWF) and will show normal ristocetin-induced binding and aggregation in the presence of human vWF. In contrast, we now report that the specific binding of vWF to the thrombin-stimulated platelets was less than 20% of normal in three patients with Glanzmann thrombasthenia. Analysis of binding isotherms was based on the assumption of one class of binding sites for vWF on the platelet membrane. Double-reciprocal plots were used to calculate maximal binding at saturation and apparent dissociation constant (Kd). In nine normals, 2.82 +/- 0.64 micrograms (+/- SD) of vWF bound to 10(8) platelets at saturation, with Kd (+/- SD) = 3.65 +/- 1.23 micrograms/ml. In two patients with thrombasthenia binding was markedly decreased and did not approach saturation. In the third patient, binding at saturation corresponded to 0.21 micrograms per 10(8) platelets, with Kd = 3.93 micrograms/ml. These findings suggest that mechanisms underlying the vWF-platelet interaction are incompletely reflected in ristocetin-dependent assay systems. Moreover, these results, in addition to those previously reported for fibronectin, suggest that the platelet defect in Glanzmann thrombasthenia is not limited to decreased binding of fibrinogen but involves several glycoproteins that are known to interact with platelets.

Blood Coagulation Factors↗
PubMed1982

Type IIB von Willebrand's disease: differential clearance of endogenous versus transfused large multimer von willebrand factor.

The abnormal multimeric composition of plasma von Willebrand factor in type IIB von Willebrand's disease is transiently corrected after infusion of 1-deamino-[8-D-arginine]-vasopressin. However, the larger multimers released into the circulation disappear more rapidly in these patients than in type I von Willebrand's disease or normals. We demonstrate that the larger multimers of normal von Willebrand factor transfused into a type IIB patient are cleared from the circulation more slowly than multimers of similar size endogenously released from tissue stores. The rate of disappearance of large von Willebrand factor multimers after infusion of cryoprecipitate is similar in IIB, IIA, and severe homozygous-like von Willebrand's disease. Platelets from the IIB patient exhibited normal ristocetin-induced binding of normal von Willebrand factor. However, like normal platelets, they bound IIB von Willebrand factor at lower ristocetin concentrations than required for normal von Willebrand factor. These findings provide evidence that absence of the larger multimers from IIB plasma is related to a molecular abnormality of von Willebrand factor rather than to enhanced affinity of abnormal tissue or cellular binding sites, as is the case in the recently described "pseudo" von Willebrand's disease and "platelet-type" von Willebrand's disease.

Blood Coagulation Factors↗
PubMed1981

Correlations between renal cortical interstitial fibrosis, atrophy of the proximal tubules and impairment of the glomerular filtration rate.

This study has confirmed impairment of the glomerular filtration rate (GFR) (increase of the serum creatinine concentration) by fibrosing processes in the renal cortical interstitium. In addition statistically significant correlations were found between the decrease of the total area of the proximal tubules and of the area of the epithelial cells and both the extent of the renal cortical interstitial fibrosis and the serum creatinine concentration. Further statistically significant positive correlations were observed between the age of the patients and both the grade of interstitial fibrosis and the serum creatinine concentration. No correlation could be established between the age of the patients and the total area of the epithelial cells of the proximal tubules. Pathogenetically it is conceivable that with progressive interstitial fibrosis the tubules become atrophic as a result of malnutrition. The function of these atrophied tubules may be disturbed, the reabsorptive capacity for NaCl impaired and consequently the GFR reduced not only by slowing of the glomerular blood flow secondary to interstitial fibrosis, but also by the tubular-glomerular feedback-mechanism.

Acute Kidney Injury↗
PubMed1980

Structure and function of the kidney in diabetic glomerulosclerosis. Correlations between morphological and functional parameters.

Histological and clinical findings in 103 middle-aged patients suffering from diabetic glomerulosclerosis (gs) (biopsy material) are reported. In diabetic gs (as in other inflammatory and non-inflammatory glomerular disease) a statistically highly significant positive correlation exists between the grade of fibrosis of the renal cortical interstitium and the serum creatinine concentration at the time of biopsy. Rank correlations exist between vessel index and relative cortical interstitial volume on the one hand as well as serum creatinine concentration on the other. Significant differences are also shown to exist between the mean values of the cortical interstitium as well as the serum creatinine concentration and the vessel index in the four grades of diabetic gs. Severe glomerular lesions may be accompanied by a normal serum creatinine concentration, only if the interstitium shows no fibrotic changes. Mild glomerular lesions, when accompanied by an interstitial fibrosis, always have elevated serum creatinine concentrations. The incidence of hypertension, proteinuria, the nephrotic syndrome and hematuria in diabetic gs appears to vary greatly. From the highly significant correlation between the cortical interstitium and the serum creatinine concentration we presume the following: Alterations of the postglomerular vessels by interstitial fibrotic changes result in an increased resistance to renal cortical blood flow with a subsequent reduction of glomerular perfusion. This reduction of the glomerular perfusion may result in a rise of the serum creatinine concentration, independently of the severity of the glomerulosclerosis. It is also conceivable that glomerular function is affected by the malfunctioning atrophic tubules in areas of interstitial fibrosis.

Biopsy↗
PubMed1977

The influence of glomerular and interstitial factors on the serum creatinine concentration in renal amyloidosis.

48 cases of renal amyloidosis (grade I-IV) were investigated morphologically (point-counting method). Statistically significant positive correlations exist between relative interstitial volume and serum creatinine concentration at the time of biopsy. In amyloidosis there are furthermore connections (positive rank correlations) between the extent of glomerular amyloidosis and renal insufficiency, although single cases of grade III show normal serum creatinine concentrations if the interstitium is not enlarged. With regard to interstitial alterations only fibrosis, not amyloid masses, seems to influence renal function, especially in the case of predamaged glomeruli (grade II to IV). The diminished renal function - reduction of the glom. filtr. rate - may be explained in the case of interstitial fibrosis by slowing of renal blood flow caused by a decreasing cross-sectional area of postglomerular vessels. Renal insufficiency seems to depend upon both the glomerular and the interstitial factor, but in grades II-IV the interstitial fibrosis is thought to be of more importance for renal function.

Amyloidosis↗
PubMed1977

Serum creatinine concentration and renal interstitial volume. Analysis of correlations in endocapillary (acute) glomerulonephritis and in moderately severe mesangioproliferative glomerulonephritis.

Renal biopsies of 44 patients with endocapillary acute glomerulonephritis (gn) and 64 patients with moderately severe mesangioproliferative gn were investigated morphometrically (point-counting-method, tubulometry). In both gn's statistically significant positive corrleations between relative interstitial volume and the concentration of serum creatinine at the time of biopsy were found. Despite severe glomerular lesions the serum creatinine concentration is not increased in most cases of endocapillary acute gn, providing the relative interstitial volume is not increased by more than 15%. Increased serum creatinine concentration without a markedly enlared interstitium was found in 11 cases of endocapillary acute gn with clinically and morphologically proven acute renal failure. In these cases the glomerular function is probably impaired by the Thurau-mechanism. In all other patients, especially in those with moderately severe mesangioproliferative gn, the serum creatinine concentration rises with an enlargement of relative interstitial volume. This reduction of renal function may be explained by a decrease to the total cross-sectional area of postglomerular vessesl, caused by interstitial fibrosis. That may possible lead to diminished renal blood flow and glomerular filtration with an increase of the serum creatinine concentration.

Acute Disease↗
PubMed1977

[Iron absorption after oral application of a combination of Fe2+-succinate and multivitamins (author's transl)].

The rate of iron absorption of Fe2+-succinate orally applied with multivitamins, was measured by means of whole-body counter in 45 subjects. The dosage was 330 mg ferrous succinate (115 mg Fe2+). Absorption was generally 4.5% (5.2 mg) in normal subjects, 8.6% (9.9 mg) in subjects with latent iron deficiency, and 29.6% (34 mg) in subjects with manifest iron deficiency. In women taking oral contraceptives and not suffering from iron deficiency, no significant increase in the iron absorption rate was measured.

Administration, Oral↗