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Biomedical subjects

D Meyer

Publications and source records attributed to D Meyer.

At least 325 records · Page 18Linked to original sources
PubMed1992

Comparison of the primary structure of the functional domains of human and porcine von Willebrand factor that mediate platelet adhesion.

Porcine von Willebrand factor (vWF) directly aggregates human platelets in vitro indicating a conformational difference between the human and porcine molecules. We amplified and directly sequenced 1242 nucleotides of porcine vWF cDNA that encodes functional domains which mediate the binding of vWF to platelets and subendothelium. The deduced amino acid sequence corresponds to residues 473-891 of the human mature vWF subunit and is 79% homologous with the human protein. Significant differences are found in two discontinuous segments thought to be involved in the binding of vWF to platelet glycoprotein Ib. Porcine vWF lacks four contiguous residues in the first segment and has two positively charged arginine residues in the second. Three point mutations associated with human type IIB von Willebrand disease in the first segment of a botrocetin binding site are at the same position as mismatches between the pig and human. The second segment of the botrocetin site is highly conserved while the third segment shows only a 60% homology.

Amino Acid Sequence↗
PubMed1992

Tooth contacts in eccentric mandibular positions and facial morphology.

Correlations between facial morphology and tooth contacts in excursive mandibular positions were studied in 75 men aged 20 to 33 years. The morphology of the dentition was verified on dental casts and the face was measured by use of roentgen cephalometry. No correlation was observed between facial morphology and the number of tooth contacts in the retruded position; however, wide dental arches and jaws displayed many contacts on protrusion. Numerous contacts on the functional side in group function were noted in individuals with a facial morphology associated with distal occlusion, such as Angle class II, division 1. Wide dental arches were associated with multiple functional-side contacts whereas tooth contacts on the nonfunctional side were related to the inclination of the mandible. A "long-face" morphology was related to contacts on the nonfunctional side. There was a negative correlation between the extent of the overbite (vertical overlap) and the number of tooth contacts on the nonfunctional side.

Adult↗
PubMed1992

Defects in type IIA von Willebrand disease: a cysteine 509 to arginine substitution in the mature von Willebrand factor disrupts a disulphide loop involved in the interaction with platelet glycoprotein Ib-IX.

Type IIA von Willebrand disease (vWD) is characterized by the loss of high and intermediate weight multimers of von Willebrand factor (vWF) from plasma. The 3' end of exon 28 in the vWF gene from four type IIA vWD patients was amplified by the polymerase chain reaction, cloned and sequenced. Sequencing identified two potential missense mutations resulting in the amino acid substitutions Arg 834-->Gln and Glu 875-->Lys in the mature vWF subunit within an area of vWF where mutations in type IIA vWD have been reported. Neither of these amino acid substitutions was found in over 100 normal alleles tested by allele specific oligonucleotide hybridization. A polymorphism (Val 802-->Leu) was identified in another patient. Other areas of exon 28 were analysed by denaturing gradient gel electrophoresis (DGGE) and DNA from one patient demonstrated an irregular DGGE pattern on the 5' end of the exon. Sequencing demonstrated an amino acid substitution of an arginine for cysteine at position 509 adjacent to an area of vWF where defects associated with type IIB vWD have been found. This substitution was not found in 100 normal chromosomes tested by restriction enzyme digestion. The Cys 509-->Arg substitution eliminates an intramolecular disulphide bridge formed by Cys 509 and Cys 695 which is important to maintain the configuration of vWF functional domains that interact with platelet glycoprotein Ib-IX.

Arginine↗
PubMed1992

Replacement therapy with virus-inactivated plasma concentrates in von Willebrand disease.

In von Willebrand disease, the goal of treatment is to correct the two laboratory hallmarks of abnormal hemostasis, i.e. the deficiency of factor VIII (FVIII) and the prolonged bleeding time (BT). Since desmopressin (DDAVP) is able to achieve both these goals in the majority of patients, it is the treatment of choice. Some patients, however, are not responsive or become refractory to DDAVP. In these, blood products maintain an important therapeutic role, and there is a need to assess the efficacy of the recently available virus-inactivated plasma concentrates, which contain both FVIII and von Willebrand factor and carry a low risk of transmitting blood-borne viruses. Our survey of the data reported in the literature indicates that all available concentrates are similarly effective in attaining high and sustained levels of FVIII after infusion. Although they often shorten or normalize the prolonged BT, that effect is less uniform. Since concentrates appear efficacious in the majority of clinical situations that require the use of blood products, they should be preferred, because of their greater safety, to cryoprecipitate produced by blood banks, which cannot be virus inactivated.

Bleeding Time↗
PubMed1992

Characterization of an endothelial protein in the developing rabbit kidney.

A new protein (EnPo 1 antigen) abundant on endothelial cells and glomerular podocytes has been characterized by means of the mouse monoclonal antibody EnPo 1. Following electrophoretical separation of rabbit kidney homogenates EnPo 1 recognized a protein with a molecular weight of 110 kDa and an isoelectric point of 5.9 in Western blots. Using immunohistological techniques, the EnPo 1 antigen has been localized in high concentrations on glomerular podocytes of different developmental stages. Furthermore, the EnPo 1 antigen was expressed on endothelial cells of all adult rabbit organs tested so far. Detailed analysis of neonatal rabbit kidney revealed the abundance of EnPo 1 antigen on both differentiated vessels as well as on immature endothelial cells and endothelium of the microvasculature. Thus, for the first time a marker for in situ investigations of angiogenic processes within the mammalian kidney is available. Analysis of kidney cryosections by confocal laser scan microscopy revealed a direct connection between mature and differentiating vessels in the outer kidney cortex. Furthermore, two differentially organized cell populations discriminated by their EnPo 1 binding pattern were localized in the embryonic renal cortex. Morphologically, these cells were not distinguishable from other mesenchymal cells.

Animals↗
PubMed1992

Activation of rat liver perisinusoidal lipocytes by transforming growth factors derived from myofibroblastlike cells. A potential mechanism of self perpetuation in liver fibrogenesis.

Rat liver perisinusoidal lipocytes (PL) cultured on uncoated plastic transform spontaneously within 6-10 d to myofibroblastlike cells (MFBlC). Parallel to the transformation the TGF alpha- and TGF beta 1-mRNA expression increased and was highest in MFBlC. Competitive radioligand binding assays demonstrated that in contrast to untransformed PL the MFBlC synthesize and secrete transforming growth factor (TGF)-alpha (15 fmol/cell per 24 h) and predominantly the latent form of TGF beta 1 (0.2 fmol/cell per 24 h). Medium conditioned by MFBlC (MFBcM) significantly stimulated PL proliferation with little effect on PL proteoglycan synthesis. By transient acidification of the MFBcM, known to activate the latent form of TGF beta 1, the stimulatory effect on PL proteoglycan synthesis was enhanced and furthermore PL transformation (measured by expression of iso-alpha smooth muscle actin and loss of retinylpalmitate) was accelerated. Preincubation of this medium with neutralizing antibodies to TGF beta resulted in (a) the growth inhibitory effect was converted to a growth stimulation and (b) the stimulatory effect on proteoglycan synthesis was abolished. In summary our data indicate that progressive activation of PL on plastic (transformation to MFBlC) leads to an enhanced expression of the TGF alpha- and TGF beta 1-mRNAs and secretion of the corresponding proteins. Medium conditioned by MFBIC stimulates proliferation, transformation, and PG synthesis of untransformed PL. These mechanisms are suggested to be relevant in self perpetuation of liver fibrogenesis.

Adipose Tissue↗
PubMed1992

[Balanced facial hydrophilicity of ioversol: a qualitative approach of hydrophilicity].

Chimiotoxicity of iodinated contrast media is essentially due to non specific hydrophobic interactions with biologic proteins and membranes. These hydrophobic interactions depend both on the whole molecular lipophilicity and on the spatial accessibility of lipophilic molecular areas. Measurements of lipophilicity by partition coefficient, partially take into account the spatial localisation of hydrophilic groups around the lipophilic area due to the 1,3,5-triiodo-benzene. These measurements have to be completed by an accurate knowledge of the three-dimensional localisation of hydrophilic groups to improve the biocompatibility of polyiodinated contrast media. The concept of evenly distributed facial hydrophilicity aims to minimize the accessibility to lipophilic area by a localisation of hydrophilic group on each plan of the benzene ring. The molecular structure of ioversol allows to put this concept in concrete form thanks to a tertiary anilide group which imposes on one hydroxy group to be located on each face of the 1,3,5-triiodo-benzene ring, providing facial hydrophilic protection.

Contrast Media↗
PubMed1992

Effect of combined peribulbar and retrobulbar injection of large volumes of anesthetic agents on the intraocular pressure.

A prospective randomized study was done in 79 patients undergoing elective routine cataract surgery in which the Kelman phacoemulsification technique was used with placement of an intraocular lens. In all the patients anesthesia was induced with both a peribulbar and a retrobulbar injection of a large volume (total 10.5 mL) of local anesthetic. The patients were randomly assigned to receive either the peribulbar (39 patients) (group 1) or the retrobulbar (40 patients) (group 2) injection first. The intraocular pressure (IOP) was measured five times during anesthesia. The mean elevation in IOP immediately after the first injection was 0.4 mm Hg in group 1, compared with 2.0 mm Hg in group 2. Twenty minutes after both injections had been given and a Super Pinky pressure device had been placed on the eye, the mean decrease in IOP from the preoperative value was 3.1 mm Hg in group 1 and 4.8 mm Hg in group 2. We conclude that a combined peribulbar and retrobulbar approach is a safe and effective alternative method of regional anesthesia for cataract surgery.

Aged↗
PubMed1992

Myasthenia gravis-like syndrome induced by topical ophthalmic preparations. A case report.

This case study reports on a 64-year-old female who presented for cataract surgery. She relayed a history of allergic responses to local anesthetics such as xylocaine, but was otherwise in good health. Upon instilling ophthalmic preparations into her eyes during routine ocular examination, she developed general muscular weakness but not other allergic-like symptoms. Further investigation established her myasthenic-like syndrome to be precipitated by an ophthalmic mydriatic preparation. She was able to undergo uneventful cataract surgery and enjoy 20/20 vision postoperatively, with proper management.

Cataract Extraction↗
PubMed1992

Molecular study of von Willebrand disease: identification of potential mutations in patients with type IIA and type IIB.

The defective von Willebrand Factor (vWF) in type IIA von Willebrand disease (vWD) has decreased binding affinity for platelet membrane glycoprotein Ib (GPIb) while in type IIB vWD, the abnormal vWF has increased affinity for this receptor. Segments of exon 28 of the vWF gene were amplified by the polymerase chain reaction and sequenced in two patients with type IIA and two patients with type IIB vWD. One type IIB patient showed an arginine to tryptophan substitution at amino acid residue 543 in the mature vWF and the other patient had a valine to methionine change at residue 553. Including these two new cases, substitutions at residues 543 and 553 now account for more than half of the documented mutations in patients with type IIB vWD. One patient with type IIA vWD showed an isoleucine to threonine change at amino acid 865. This substitution has been reported in another patient with type IIA vWD. The other patient showed a novel proline to serine change at residue 885. The C to T nucleotide transition which causes the amino acid change was not found in over 100 normal chromosomes tested by allele specific oligonucleotide hybridization and was linked to type IIA vWD in the family. This potential mutation is more carboxyterminal in the vWF subunit than other reported mutations in type IIA vWD. It is apparent that mutations associated with type IIA vWD are not as tightly grouped as defects in type IIB vWD, supporting the evidence that the type IIA vWD phenotype is generated by diverse mechanisms.

Base Sequence↗
PubMed1992

South African obstetricians' views on caesarean section.

The widespread increase in the rate of caesarean sections performed in the Western world has become a cause for concern. In this country, two systems of health care exist, one provided by the State and the other based on private practice. A high incidence of caesarean sections has been reported, especially among private practitioners. This study investigated doctors' perceptions of caesarean section practices and explored the availability of facilities which could help to reduce the high caesarean section rate. Questionnaires were mailed to all registered obstetricians. Of these 45.2% (233) responded. Findings indicate that private obstetricians are more likely to perform caesarean sections even though they do have good facilities available to monitor or assess difficult deliveries. Other factors influencing their practice are also explored.

Attitude of Health Personnel↗
PubMed1992

A directed search for mutations in hemophilia A using restriction enzyme analysis and denaturing gradient gel electrophoresis. A study of seven exons in the factor VIII gene of 170 cases.

Genomic DNA from 170 unrelated hemophilia A patients was examined for gene defects in the coding region of the Factor VIII gene. Exons 18, 22-24 and 26 contain a CGA codon for arginine within the recognition sequence for the restriction enzyme Taq I. These five sites were amplified by the polymerase chain reaction and tested for abnormal Taq I restriction patterns. In five cases, the enzyme Taq I failed to digest the amplified fragments. Direct sequencing of the amplified products demonstrated a C to T transition in the coding strand of exons 18, 22 and 24 in three severe hemophilia A patients resulting in TGA termination codons. Two patients showed G to A transition in exons 24 and 26 reflecting a C to T transition in the non-coding strand substituting a glutamine for an arginine. Three deletions involving exon 26 and one exons 23-26 were found in severe hemophiliac patients. In contrast, exons 23 and 24 failed to amplify in one patient with a moderate form of the disease suggesting an in-frame splicing of exons 22 and 25. Exon 8 and the 3' end of exon 14 were analyzed by denaturing gradient gel electrophoresis (DGGE). Two patients with a moderate form of the disease demonstrated an abnormal electrophoretic pattern in exon 8 and sequencing demonstrated missense mutations at codon 372 for arginine within a thrombin activation site. One missense mutation was a C to T transition substituting cysteine for arginine and the other was an infrequent G to C transversion at an adjacent nucleotide changing the same arginine to proline.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1992

Evaluation of peritoneal fluid following intestinal resection and anastomosis in horses.

Postoperative abdominal fluid changes were compared in 2 groups of horses; those undergoing double small-colon resection and anastomosis (n = 10) and those undergoing exploratory celiotomy alone (n = 5). Peritoneal fluid was collected before surgery and on postoperative days 1, 3, 5, and 7. Total and differential nucleated cell counts, RBC numbers, and total protein and fibrinogen concentrations were evaluated. In both groups, all values were significantly higher than normal on the first postoperative day (after small-colon resection and anastomoses, WBC = 130,350 +/- 23,310 cells/microliters, RBC = 7,389,000 +/- 6,234,000 cells/microliters, total protein = 3.63 +/- 0.16 g/dl; after exploratory celiotomy alone, WBC = 166,620 +/- 34,340 cells/microliters, RBC = 295,000 +/- 86,070 cells/microliters, total protein 4.38 +/- 0.54 g/dl). The number of total peritoneal nucleated cells and RBC significantly decreased after the first postoperative day, whereas total protein and fibrinogen concentrations, percent neutrophils, and percent mononuclear cells remained unchanged. None of the values had returned to normal by postoperative day 7 (after small-colon resection and anastomoses, WBC = 45,600 +/- 8,765 cells/microliters, RBC = 95,390 +/- 53,380 cells/microliters, total protein = 4.39 +/- 0.23 g/dl; after exploratory celiotomy alone, WBC = 43,340 +/- 7,746 cells/microliters, RBC = 12,860 +/- 11,790 cells/microliters, total protein = 3.92 +/- 2.20 g/dl.) The resection and anastomosis group had a significantly lower total protein concentration on the first postoperative day and a significantly higher mean total RBC count over the entire 7-day postoperative evaluation than did horses that underwent celiotomy alone. Other values in the 2 groups of horses did not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗
PubMed1991

One experience with 'lower' or 'higher' intensity stressors, respectively enhances or diminishes responsiveness to haloperidol weeks later: implications for understanding drug variability.

This laboratory has previously shown that acute exposure to a variety of brief stressful events can have a very long-lasting influence on subsequent responsiveness to pharmacological and non-pharmacological stressors. In some cases the response to these agents is enhanced, while in others it is diminished: the common denominator being that in each instance the influence of the initial stressor grows stronger with the passage of time. Here, we identify one factor that determines which time-dependent effect is manifest. In 3 separate experiments, male rats were subjected to a single exposure to stressors of either lower or higher intensity and their effects on haloperidol-induced catalepsy and dopamine and dihydroxyphenylacetic acid levels in the nucleus accumbens and medial frontal cortex, measured either 1-2 h or 2 weeks later. The stressors were either environmental (needle jab or 1 h of immobilization), metabolic (200 or 750 mg/kg, i.p. of 2-deoxy-D-glucose), or no effect on haloperidol-induced catalepsy when stressors preceded such behavioral testing by 1-2 h. By contrast, when the interval was 2 weeks, the lower-intensity stressors all increased haloperidol catalepsy, whereas the higher-intensity stressors decreased the same response. In other words, a process that progressed with the passage of time was observed regardless of whether sensitization or diminution of haloperidol's action occurred. In contrast to the uniform bipolar behavioral effects observed, depending on the intensity of the prestressor, the neurochemical findings failed to show any evidence of bipolarity whatever.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

The binding domain of von Willebrand factor to sulfatides is distinct from those interacting with glycoprotein Ib, heparin, and collagen and resides between amino acid residues Leu 512 and Lys 673.

A series of proteolytic fragments of human von Willebrand Factor (vWF) was purified to characterize the functional site that supports its interaction with sulfatides. SpIII, an N-terminal homodimer generated by V-8 protease (amino acids [AA] 1 to 1365), bound to sulfatides in a dose-dependent and saturable way. SpIII also totally inhibited the binding of vWF to sulfatides and SpIII binding was completely abolished by vWF. In contrast, SpII, the complementary C-terminal homodimer (AA 1366 to 2050), did not exhibit any binding affinity for sulfatides. Four purified fragments overlapping the sequence of SpIII were also tested for their ability to interact with sulfatides. An N-terminal monomeric 34-Kd fragment (P34, AA 1 to 272) generated by plasmin, a central monomer (SpI, AA 911 to 1365) produced by digestion with V-8 protease, and a tetrameric fragment III-T2 (comprising a pair of the two sequences AA 273 to 511 and AA 674 to 728) produced by secondary digestion of SpIII with trypsin did not interact with sulfatides. In contrast, a monomeric 39/34-Kd fragment produced by dispase (AA 480 to 718) bound specifically and with a high affinity to sulfatides and totally displaced vWF or SpIII binding. Conversely, binding of the 39/34-Kd species was totally abolished by vWF or SpIII. Thus, a functional site responsible for sulfatide binding was localized between AA 480 and 718 and comparison of the binding properties of the 39/34-Kd and III-T2 fragments indicated that the sequence 512 to 673 is necessary for the binding to sulfatides. Further mapping of this new functional domain of vWF, based on experiments of competitive inhibition of binding by either heparin or monoclonal antibodies directed toward vWF, showed that the site interacting with sulfatides is distinct from those involved in binding to platelet glycoprotein Ib, collagen, or heparin. This finding was confirmed by experiments using synthetic peptides which also indicated that the sequence comprising AA 569 to 584 is part of the sulfatide-binding domain or influences its activity.

Amino Acid Sequence↗
PubMed1991

Duplication of a methionine within the glycoprotein Ib binding domain of von Willebrand factor detected by denaturing gradient gel electrophoresis in a patient with type IIB von Willebrand disease.

von Willebrand disease (vWD) type IIB is characterized by an increased reactivity of von Willebrand factor (vWF) with platelets and a lack of large multimers. Exon 28 of the vWF gene encodes for functional domains involved in the binding of vWF to GPIb, and it is presumed that the defects in type IIB vWD lie within or adjacent to these functional domains. We screened overlapping DNA fragments generated by the polymerase chain reaction (PCR) that spanned the 1,379 bp of exon 28 of a type IIB vWD patient using denaturing gradient gel electrophoresis (DGGE). To increase the power of DGGE to detect base changes, we used the PCR to attach a G + C-rich sequence. In the type IIB patient, a DNA fragment at the 5' end of exon 28 demonstrated homoduplex and heteroduplex complexes after DGGE, a pattern characteristic of heterozygous genes after melting and reannealing during the PCR. Sequencing of the cloned insert from the patient showed a duplication of an ATG in one gene coding for a Met at amino acids 540 to 541 in the mature vWF subunit. This duplication leads to three consecutive methionines in the patient's sequence. The duplicated Met resides within a disulfide bond loop proposed to be important in the function of the GPIb binding domain of vWF. The patient's nephew, who also has type IIB vWD, showed the same duplicated codon, linking the defect to the abnormal phenotype in this family. These nucleotide changes were not found in 100 chromosomes analyzed either by DGGE or hybridization with an allele specific oligonucleotide containing the duplicated ATG codon. In addition, the same oligonucleotide hybridized only to DNA from type IIB vWD individuals and not to DNA from normal members of the family. Therefore, we conclude that this duplicated Met modifies the GPIb binding domain of vWF and causes type IIB vWD in this family.

Base Sequence↗