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Biomedical subjects

D Meyer

Publications and source records attributed to D Meyer.

At least 523 records · Page 29Linked to original sources

Platelet membrane glycoproteins implicated in ristocetin-induced aggregation. Studies of the proteins on platelets from patients with Bernard-Soulier syndrome and von Willebrand's disease.

The antibiotic ristocetin only aggregates platelets in the presence of plasma von Willebrand factor. Platelets from patients with Bernard-Soulier syndrome do not aggregate upon addition of ristocetin although, in contrast to von Willebrand's disease, plasma levels of factor VIII complex (factor VIII clotting activity, von Willebrand factor activity, and von Willebrand antigen) are normal. The membrane surface of normal platelets was modified and compared to the surface of platelets from a patient with Bernard-Soulier syndrome in an attempt to identify the receptor involved in von Willebrand factor-ristocetin-induced aggregation. After the incubation of washed normal platelets with a preparation of ristocetin previously shown to contain a proteolytic contaminant, the aggregation response is significantly decreased on addition or normal plasma. Analaysis by gel electrophoresis of such platelets when stained for carbohydrate revealed a decrease in the relative amounts of membrane glycopro-eins. Chymotrypsin-treated normal platelets had less membrane glycoproteins in addition to giving a reduced aggregation response in ristocetin-induced aggregation. Staining of gels for protein and carbohydrate indicated that there was an extensive change in the surface of Bernard-Soulier platelets, whereas those from patients with von Willebrand's disease appeared the same as normal. Platelets from patients were labeled by the lactoperoxidase iodination technique. Not only was the relative intensity of staining of platelet-specific proteins and glycoproteins changed in Bernard-Soulier platelets, but the iodination of the glycoproteins on the membrane surface relative to other membrane constituents was lower. In contrast, platelets from patients with von Willebrand's disease showed a normal exposure of membrane components. These data suggest therefore that membrane glycoproteins may play a functional role in ristocetin-induced aggregation.

Binding Sites↗

Characterization of human anti-factor VIII antibodies purified by immune complex formation.

Anti-factor VIII antibodies from three hemophilia A patients were selectively isolated by immune complex formation and secondary precipitation with polyethylene glycol. These antibodies were characterized as IgG, with only one type of light chains (kappa) and a mixture of IgG3 and IgG4 heavy chains. This finding indicated that stable complexes of factor VIII and homologous anti-factor VIII antibodies could be obtained, and that the immunologic response to the infusion of homologous factor VIII was oligoclonal rather than monoclonal in these patients.

Antibodies↗

The glomerular mesangium in hypertension: a morphometrical comparison of nephrosclerosis with mesangioproliferative glomerulonephritis on renal biopsies.

Glomerular changes were morphometrically studied in renal biopsies of 27 cases of nephrosclerosis showing clinically benign or malignant hypertension and of 15 cases of mild mesangioproliferative glomerulonephritis with hypertension. In nephrosclerosis, there was a mild increase in mesangial matrix without cell proliferation. The degree of the mesangial changes varied little despite a large variation in blood pressure and showed no significant difference between benign and malignant hypertension. In mild mesangioproliferative nephritis with hypertension, mesangial matrix, as well as the number of mesangial cells, showed an increase of varying degree. A quantitative assessment of the mesangium was proved effective in differentiating the glomerular changes in nephrosclerosis from those in mesangioproliferative nephritis with hypertension.

Adult↗

The size of the juxtaglomerular apparatus in glomerulonephritis with the nephrotic syndrome: a morphometrical study of renal biopsies.

The juxtaglomerular apparatus was histoplanimetrically studied in renal biopsies of 65 cases of membranoproliferative glomerulonephritis and 64 cases of minimal proliferative intercapillary glomerulonephritis (MPI) ("minimal changes"). The juxtaglomerular cell complex (JGC complex) consisting of the epithelioid cells (granular cells) and the Goormaghtigh's cells (agranular or lacis cells) was significantly enlarged in the nephrotic syndrome. 10 to 14 days' duration of the nephrotic syndrome was shown to be sufficient to bring about an enlargement of the JGC complex. After a successful treatment of the nephrotic syndrome with steroids, there was no enlargement of the JGC complex. The enlarged JGC complex persisted despite steroid treatment in the steroid-resistant nephrotic syndrome, although a mild suppressive effect of steroids on the size of the JGC complex was observed. There was no significant relationship between hypertension and the size of the JGC complex. Creatinine retention tended to be associated with an enlargement of the JGC complex. The macula densa was not enlarged in the nephrotic syndrome, in contrast to the enlarged JGC complex.

Age Factors↗

Nuclease digestion of synthetase x tRNA complexes.

Phenylalanyl-tRNA and seryl-tRNA synthetase protect strongly though not completely their cognate tRNAs against nuclease attack, as had been shown previously. In an investigation of the mechanism of protection it was demonstrated that the low susceptibility of phenylalanyl-tRNA-synthetase x tRNA-Phe complexes to nucleases is due to free tRNA present in equilibrium with synthetase. The equilibrium can be shifted by an excess of synthetase or by dilution of the complex. It therefore appears that synthetase competes with the nuclease for free tRNA. Degradation of the complex is low, however, because under the conditions of partial digestion the synthetase has a greater affinity for the tRNA than does the nuclease. Fragmented tRNAs, as they are formed during partial nuclease digestion, bind to synthetase to different degrees. tRNA-Phe with a lesion in the dihydrouridine loop binds very poorly whereas a nick in the anticodon loop reduces the strength of binding to a much lesser extent. In a systematic study of the stoichiometry of protection it was confirmed that under standard conditions one phenylalanyl-tRNA synthetase protects one tRNA-Phe and one seryl-tRNA synthetase two tRNA-Ser molecules against nuclease attack. Under certain conditions, however, (concentration of the complex higher than 10 mu-M, or alternately in buffers of low ionic strength) it is observed that phenylalanyl-tRNA synthetase binds up to 1.6 molecules tRNA-Phe. In the serine system, these special conditions do not affect the binding properties of seryl-tRNA synthetase.

Amino Acyl-tRNA Synthetases↗

Cytomegalovirus in tears from patients with normal eyes and with acute cytomegalovirus chorioretinitis.

Cytomegalovirus (CMV) was recovered from the tears in eight of 41 (19.5%) children excreting CMV in their urine or saliva. Tear excretors were all immunosuppressed children with acute lymphocytic leukemia. Three had active CMV chorioretinitis and five did not develop retinal disease in nine to 15 months of observation. To our knowledge this was the first report of the recovery of CMV from tears and of acquired CMV chorioretinitis in children. One patient with active chorioretinitis presented with a disciform elevation of the macula. Therapy with adenine arabinoside (ara-A) or idoxuridine was ineffective in two patients while a third patient treated with ara-Apossibly had a more rapid recovery. However, the significance is uncertain due to the unusual disease presentation and lack of data regarding the nature of cytomegalic inclusion disease chorioretinitis. Areas of retinal calcification were present at autopsy in one patient.

Adult↗

Heterogeneity in biological activity of human factor VIII antibodies.

Antibodies against factor VIII collected from six patients were studied for their effect on factor-VIII coagulant activity, Willebrand factor activity (WF) and factor-VIII-related antigen. The results demonstrate differences between individual antibodies; some acting primarily as anti factor VIII, others inhibiting both after VIII and WF. Differences in effect between plasma and serum indicate that the process of coagulation alters the interaction of these antibodies.

Factor VIII↗

Morphometric studies of the juxtaglomerular apparatus in perimembranous glomerulonephritis.

In 23 cases of perimembranous glomerulonephritis (PGN, membranous nephropathy), the juxtaglomerular cell complex (JGC-complex) in early postmortal (2 cases) and bioptically obtained specimens (21 cases) was investigated quantitatively by planimetry. The results were correlated with the stage of the PGN and the clinical findings. A statistically significant increase in mean size of the JGC-complex was found in perimembranous glomerulonephritis compared with the control group (p smaller than 0.005). Comparing the different morphological stages of PGN, the size of the JGC-complex was increased and the serum creatinine level raised in stages 3 and 4. In hypertensive patients with perimembranous glomerulonephritis, the serum creatinine levels were significantly raised as compared with the normotensive group.

Adolescent↗

Problems in the detection of carriers of haemophilia A.

Factor VIII activity and factor VIII related--or Willebrand--antigen were studied in 49 known carriers of haemophilia A and 31 normal women, and the data were analysed by four statistical approaches. Sixteen per cent of normals and 18% of carriers were misclassified, overlapping with the other group. Although the percentage of carriers detected is higher when taking into account the results of both biological and immunological factor VIII, it is lower than others recently reported, and the discrepancies between the results obtained are discussed.

Factor VIII↗