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Biomedical subjects

D Meyer

Publications and source records attributed to D Meyer.

At least 397 records · Page 22Linked to original sources
PubMed1988

Carrier detection in severe (type III) von Willebrand disease using two intragenic restriction fragment length polymorphisms.

DNA from a family with a female member affected with severe (type III) vWD was analysed using three restriction enzymes and a partial vWF cDNA probe. Two restriction fragment length polymorphisms (RFLPs) detected with the enzymes Bgl II and Xba I proved to be informative in this family. A 36.0 Kb allele demonstrated with the enzyme Xba I was rare in the general population but very important in this family for segregation analysis of the alleles and their association with the putative defective chromosome. The propositus was homozygous for the 36.0 Kb Xba I polymorphic band and heterozygous for the Bgl II polymorphism. She was the only member of the family showing this allelic pattern. The linkage of the alleles could be determined because her mother was homozygous for the 9.0 Kb Bgl II polymorphism but heterozygous for the Xba I polymorphism. The segregation of the alleles could be traced to the proband's son and a niece. The genotypic analysis revealed that her niece could be considered as carrying a defective gene for severe vWD.

Alleles↗
PubMed1988

Haemophilia A in a female: study of a family using intragenic and extragenic restriction site polymorphisms.

Restriction fragment length polymorphisms (RFLPs) were studied in a large Algerian family which includes 6 haemophiliacs and a previously described case of female haemophilia A. The female propositus is 66 years old with a normal karyotype. Her parents are first cousins. Her 3 sons are haemophiliacs and her 3 daughters with affected children are obligate carriers. The proband has an excessive bleeding tendency and markedly reduced levels of F.VIII (VIII C 0.03 U/ml, VIII Ag 0.01 U/ml) with elevated vWF Ag (2.30 U/ml), similar to the levels observed in affected males from the family. Four RFLPs can be identified by Southern blotting after digesting genomic DNA with the restriction enzymes Bcl I, Bgl I, Kpn I/Xba I and Taq I and hybridization with a 647 bp Stu I/Sca I F.VIII genomic probe, a 1.8 Kb EcoRI F.VIII cDNA probe, a 1.0 Kb EcoRI/Sst I fragment of intron 22 and the extragenic probe ST 14, respectively. With these four RFLPs, the propositus was found to be homozygous for the alleles segregating in this family with the abnormal X-chromosome. The carrier status was proven in a granddaughter and excluded in another. In conclusion, this RFLP linkage analysis is another argument to suggest that the propositus, a rare case of female haemophilia, is homozygous for the abnormal gene.

Aged↗
PubMed1988

The human gene for von Willebrand factor. Identification of repetitive Alu sequences 5' to the transcription initiation site.

The region at the 5' end of von Willebrand factor gene was cloned by screening genomic libraries with a partial von Willebrand factor cDNA probe and oligonucleotides complementary to areas of von Willebrand factor mRNA at the extreme 5' end of the untranslated region. The sequence 2158 bp upstream of the transcription initiation site, the first exon and first exon-intron junction is reported. The first exon includes the entire 5' untranslated sequence (250 bp) and the translation initiation codon starts the second exon, suggesting an unusual control mechanism for the cell specific expression of von Willebrand factor. An AT-rich region resembling a TATA box is found 32 bp upstream of the transcription initiation site. At -1030 and -1806 nucleotides 5' of the TATA box are two repetitive Alu sequences of approximately 300 bp. Recombinant events at these Alu sequences could result in some clinical forms of von Willebrand disease involving transcriptional defects.

Base Sequence↗
PubMed1988

A conserved epitope on several human vitamin K-dependent proteins. Location of the antigenic site and influence of metal ions on antibody binding.

A murine monoclonal antibody (designated H-11) produced by injecting mice with purified human protein C was found to bind several human vitamin K-dependent proteins. Using a solid-phase competitive radioimmunoassay with antibody immobilized onto microtiter plates, binding of 125I-labeled protein C to the antibody was inhibited by increasing amounts of protein C, prothrombin, and Factors X and VII over a concentration range of 1 X 10(-8) to 1 X 10(-6) M. Other vitamin K-dependent proteins including Factor IX and protein S did not inhibit or inhibited only at the highest concentration binding of radiolabeled protein C to the immobilized antibody. Chemical treatment of prothrombin with a variety of agents including denaturation by sodium dodecyl sulfate, reduction with mercaptoethanol followed by carboxymethylation with iodoacetic acid, citraconylation of lysine residues, removal of metal ion with EDTA, or heat decarboxylation did not destroy the antigenic site recognized by the antibody as measured by immunoblotting of prothrombin or prothrombin derivative immobilized onto nitrocellulose. Immunoblotting of purified vitamin K-dependent polypeptides with the monoclonal antibody following sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrophoretic transfer to nitrocellulose indicated that the antigenic site was found on the light chains of protein C and Factor X. Chymotrypsin digestion of prothrombin and isolation on QAE-Sephadex of the peptide representing amino-terminal residues 1-44 of prothrombin further localized the antigenic site recognized by the monoclonal antibody to the highly conserved gamma-carboxyglutamic acid-containing domain. The exact location of the antigenic determinant for antibody H-11 was established using synthetic peptides. Antibody H-11 bound specifically to synthetic peptides corresponding to residues 1-12 of Factor VII and 1-22 of protein C. Comparison of protein sequences of bovine and human vitamin K-dependent proteins suggests that the sequence Phe-Leu-Glu-Glu-Xaa-Arg/Lys is required for antibody binding. The glutamic acid residues in this peptide segment are the first 2 gamma-carboxyglutamic acid residues near the amino-terminal end in the native proteins. Increasing concentrations of Ca2+, Mg2+, or Mn2+ partially inhibited binding of 125I-protein C to the antibody in a solid-phase assay system with half-maximal binding observed at divalent metal ion concentrations of 2, 4, and 0.6 mM, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Treatment of promyelocytic leukemia during pregnancy. A case report and review of the literature.

In spite of the fact that acute promyelocytic leukemia during pregnancy is rare and that there is little precedent in the literature for treatment with combined chemotherapeutic agents, the rate of success with current chemotherapeutic regimens is very encouraging. Judging from previous reports and our own experience, it is possible to give combination chemotherapy to pregnant women with AML/APL with the result that mother and infant survive, whereby the incidence of complication is within an acceptable range. No comprehensive studies on life-time teratogenic or carcinogenic effects are available at present.

Adolescent↗
PubMed1988

Effect of sodium chloride and sodium bicarbonate on blood pressure in stroke-prone spontaneously hypertensive rats.

1. To test the hypothesis that NaCl increases blood pressure, while NaHCO3 does not, we measured the effect of an NaHCO3-containing mineral water on blood pressure in stroke-prone spontaneously hypertensive (SHR-SP) and Wistar-Kyoto (WKY) rats. We compared mineral water with equimolar amounts of NaCl and demineralized drinking water in six groups of 20 rats each over 24 weeks. 2. NaCl consistently increased blood pressure in both SHR-SP and WKY compared with demineralized water, while mineral water did not. 3. We studied the possible role of sodium-regulating hormones. Sodium, potassium-dependent adenosine triphosphatase activity was decreased by NaCl and by age, but not by mineral water. The concentration of atrial natriuretic peptide was greater in SHR-SP, but was not influenced by the two regimens. Components of the renin-angiotensin-aldosterone system and 18-hydroxydeoxycorticosterone tended to decrease with NaCl, but not with mineral water. 4. Plasma pH values in the six groups of rats were not different; however, SHR-SP had consistently lower PCO2 and HCO3- values and higher anion gap values than WKY rats. These values were not influence by the two regimens. 5. NaCl elevates blood pressure in SHR-SP while NaHCO3 does not. The changes in hormones regulating sodium homoeostasis suggest that NaCl induces volume expansion while NaHCO3 does not. The effect may be related to influences on renal sodium reabsorption by chloride and bicarbonate. The possible role of increased proton excretory activity in SHR-SP remains to be determined.

Animals↗
PubMed1988

Gd-DOTA, a potential MRI contrast agent. Current status of physicochemical knowledge.

The complex (Gd-DOTA) meglumine has recently been used as an MRI contrast agent in humans. Due to its particularly interesting physicochemical properties, the risk of in vivo dissociation of the complex is reduced. Indeed, as a result of the macrocyclic nature of the DOTA ligand, Gd-DOTA appears very stable, demonstrating a calculated conditional stability constant of 10(22.19) at pH = 7. Other characteristics making Gd-DOTA a positively attractive compound include slow dissociation kinetics inherent in the rigidity of the macrocycle and marked specific affinity of DOTA for gadolinium in comparison with other endogenous ions. Finally, although the relaxivity R1 of Gd-DOTA at 20 MHz appears similar to that of Gd-DTPA, Gd-DOTA demonstrates higher paramagnetic efficacy at low field strength due to greater symmetry of the complex. Such promising properties open up wide prospects for the use of Gd-DOTA in MRI.

Contrast Media↗
PubMed1988

Identification of a CpG mutation in the coagulation factor-IX gene by analysis of amplified DNA sequences.

In a family with no previous bleeding history, the sister of a single, severely affected haemophilia B patient requested carrier detection and prenatal diagnosis. In Southern blots, using Taq I digested DNA and a factor-IX cDNA probe, a normal invariant band at 1.6 kb was missing in the haemophiliac suggesting the loss of the Taq I site at the 5' end of exon h. A 162 bp sequence which includes the suspected mutant region was amplified by the polymerase chain reaction in each DNA. Two oligonucleotide probes were synthesized and differed by only one base pair which substituted a T for C in the normal Taq I recognition sequence. The amplified DNA was dot-blotted and hybridized with the labelled probes. The altered sequence hybridized to DNA from the affected individual, his sister and her fetus and not to DNA from the normals. The mutation, involving the haemophiliac, his mother, his sister and her fetus, transforms a CGA codon that encodes for arginine in the catalytic domain of the protein into a UGA stop codon.

Adult↗
PubMed1988

Testosterone-secreting adrenocortical tumor in a pubertal girl. Case report and review of the literature.

A girl aged 12 years and 10 months presented with deepening of the voice first noted 7 months earlier. Pubertal development was almost completed. The girl had regular monthly menses and no signs of hirsutism, clitoris enlargement or Cushing's disease. Serum testosterone was about threefold above normal, whereas dehydroepiandrosterone was in the upper normal range. The 17-ketosteroids as well as the gas-chromatographically analyzed 5 alpha and 5 beta derivatives of testosterone from urine were slightly increased. Other serum and urinary steroids were normal. Dynamic tests of the endocrine function exhibited inconclusive results. Ultrasonography revealed no ovarian cysts. A small, left-sided adrenal mass was identified by computed axial tomographic scan and removed by surgery. There were no signs of local metastasis nor of vascular extension. The histopathological diagnosis was adrenocortical carcinoma. 5 months after surgery, the preoperatively elevated steroid levels had returned to normal.

Adolescent↗
PubMed1988

Effect of high calcium diet on magnesium, catecholamines, and blood pressure of stroke-prone spontaneously hypertensive rats.

To test the effect of a high dietary calcium intake on blood pressure, we fed stroke-prone spontaneously hypertensive (SHR-SP) and Wistar-Kyoto rats (WKY) diets containing (a) 0.25% Ca/0.08% Mg, (b) 4.0% Ca/0.02% Mg, and (c) 4.0% Ca/0.08% mg, beginning at 6 weeks of age. SHR-SP and WKY rats receiving 4% Ca with the lower Mg content had lower blood pressures, hypomagnesemia, and hypomagnesuria, and grew poorly. SHR-SP receiving 4% Ca and the higher Mg diet had blood pressures no different from those of rats receiving the 0.25% Ca diet, in spite of having lower body weights. Rubidium flux studies in erythrocytes were not influenced by Ca or Mg in the diets. Plasma phosphate values were moderately reduced in rats receiving 4% Ca diets. Epinephrine and norepinephrine values were higher in SHR-SP than in WKY rats. Norepinephrine increased with stress in both strains, independent of diet. Epinephrine values were lower in SHR-SP receiving the 4% Ca diets and showed less of an increase with stress compared to SHR-SP receiving the 0.25% Ca diet. After 26 weeks of diets, SHR-SP and WKY rats were given 0.9% NaCl in their drinking water. NaCl increased blood pressure in SHR-SP irrespective of Ca content of the diet. These data suggest that a high Ca diet influences Mg homeostasis and adrenal medullary function in SHR-SP. Further, SHR-SP appear resistant to any blood pressure lowering effect of Ca irrespective of NaCl intake.

Animals↗
PubMed1988

von Willebrand factor-mediated platelet adhesion to collagen involves platelet membrane glycoprotein IIb-IIIa as well as glycoprotein Ib.

Monoclonal antibodies (MAbs) directed toward distinct functional domains of human von Willebrand factor (vWF) were used to probe the involvement of platelet membrane receptors glycoprotein Ib (GPIb) and glycoprotein IIb-IIIa (GPIIb-IIIa) in vWF-mediated platelet adhesion to collagen in flowing blood. Among nine MAbs to vWF, MAb H9 inhibits binding of vWF to GPIb, MAb 9 blocks binding of vWF to GPIIb-IIIa, and MAbs B200 through B204 inhibit binding of vWF to collagen. Collagen-coated cover slips were exposed to human citrated blood at shear rates varying from 200 to 2600 sec-1 in parallel-plate perfusion chambers. Blood was reconstituted with washed radiolabeled platelets, erythrocytes, and citrated autologous plasma previously incubated with MAb IgG or F(ab')2. Platelet-collagen interactions were estimated by radioactive counting and by quantitative morphometry. Inhibition of 70% of platelet adhesion was observed at a concentration of 20 micrograms/ml MAb 9, similar to that observed with MAbs H9 or B202. The effect of each MAb was dose dependent, and their inhibitory effect on platelet adhesion was also shear rate dependent. Virtually 100% inhibition was observed at 2600 sec-1 shear rate when a mixture of the MAbs (H9 + 9 + B202) was added to reconstituted blood. Thus, blocking three functional domains of vWF virtually abolishes platelet-collagen adhesion at high shear rates, indicating that normal adhesion to collagen is mediated through binding of vWF to collagen and to both platelet membrane GPIb and GPIIb-IIIa.

Adult↗