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D Meyer

Publications and source records attributed to D Meyer.

At least 217 records · Page 12Linked to original sources
PubMed1997

Physical, chemical and biological evaluations of CMD-A2-Gd-DOTA. A new paramagnetic dextran polymer.

PURPOSE: We investigated the synthesis and physical, chemical and biological characterisation of a carboxymethyl-dextran polymer substituted with the paramagnetic macrocyclic complex Gd-DOTA using an amino spacer. MATERIAL AND METHODS: The product was synthesised in 4 steps. Using rigorous purification conditions in each step, a polymer was obtained, i.e. CMD-A2-Gd-DOTA, whose polydispersity profile was comparable to the initial dextran (I = 1.66-Mw = 50.5 kDa). Approximately 22% of the glucose groups were replaced by Gd-DOTA and 39% were replaced by carboxyl groups. The paramagnetic efficacy of the polymer was 3 times higher than Gd-DOTA alone, which suggests that the injected doses of Gd(III) can be reduced. The vascular residence time of the polymer was measured in rats and rabbits, showing that the pharmacokinetics of the product is similar whatever the dose. Forty-five percent of the product was excreted in urine after 24 h and 1.64% was found in the liver. No acute toxicity was observed at the maximum dose injected (> 5 mmol Gd/kg) and the general biocompatibility of the product tested in vitro was comparable to that of Gd-DOTA. RESULTS AND CONCLUSION: These results show the advantages of using paramagnetic macrocyclic complexes in the synthesis of macromolecules to preserve biological stability, in contrast with linear chelates. Additional studies will be carried out to demonstrate the benefits of this type of product, particularly in functional imaging.

Animals↗
PubMed1997

Ets-1 and Ets-2 proto-oncogenes exhibit differential and restricted expression patterns during Xenopus laevis oogenesis and embryogenesis.

Xenopus XI-ets-1 and XI-ets-2 are maternally expressed. From late oogenesis to early embryogenesis their transcripts are localized to the animal pole and the intermediate zone, suggesting a function in the differentiation of animal blastomeres and future mesoderm. Their presence at the level of germ plasm suggests also a role in the differentiation of the germinal lineage. Both zygotic genes are expressed ubiquitously beginning at MBT, and then restricted to a circumblastoporal collar. In neurula and tailbud stages, ets-1 and ets-2 transcripts are detected in neural crest cells and their derivatives. Specific transcription can also be observed for ets-1 in the hemangioblastic precursors, in endothelial cells of the forming heart and blood vessels. Ets-2 is itself specifically expressed in the putative pronephros and in the forming pronephric tubules and extending pronephric duct. Like another member of the ets-gene family (XI-fli), both genes are transcribed in regions of the embryo undergoing important morphogenetic modifications, especially in migrating cells and/or along their migration pathways. We postulate that these genes orchestrate modifications of cellular adhesion. Changes in the expression of cadherins and integrins repertories would be consistent with such a role and could account for the phenotypes we reported earlier for XI-fli overexpression. Such a role would be critical for tumor cell dissemination, in addition to the one already ascribed to ets-1 in the expression of proteases specific for the extracellular matrix.

Animals↗
PubMed1997

The CrmA- and TPCK-sensitive pathways that trigger oligonucleosome-sized DNA fragmentation in camptothecin-induced apoptosis: relation to caspase activation and high molecular weight DNA fragmentation.

Abstract: In human B lymphoma Namalwa variant cells expressing the serpin-like CrmA protein, the kinetics of oligonucleosome-sized DNA fragmentation was retarded compared with that of control Namalwa cells following camptothecin treatment. However, no difference in the kinetics of high molecular weight DNA fragmentation was observed between the two lines after camptothecin treatment. Similar delay and inhibition of the oligonucleosome-sized DNA fragmentation was observed in human B lymphoma Namalwa and monocytic-like leukemia U-937 cells coincubated in the presence of various concentrations of N-tosyl-L-phenylalanyl chloromethylketone and camptothecin. The effect of N-tosyl-L-phenylalanyl chloromethylketone was similar to that of CrmA and did not prevent the appearance of high molecular weight DNA fragments. Similar suppression of camptothecin-induced internucleosomal DNA fragmentation was also observed in a cell-free system when cytosolic extracts obtained from camptothecin-treated Namalwa and U-937 cells were coincubated with untreated nuclei in the presence of N-tosyl-L-phenylalanyl chloromethylketone. Furthermore, N-tosyl-L-phenylalanyl chloromethylketone had no significant effects on caspase-3-like activities in camptothecin-treated Namalwa and U-937 cells. Hydrolysis of Ac-Asp-Glu-Val-Asp-amino-4-methylcoumarin, a fluorogenic substrate with caspase-3-like activities, was detected in extracts prepared from camptothecin-treated Namalwa and U-937 cells with no apparent difference in the time courses of caspase-3-like activation in the absence or presence of N-tosyl-L-phenylalanyl chloromethylketone. Similarly, N-tosyl-L-phenylalanyl chloromethylketone was a weak inhibitor of caspase-3-like activities in vitro. Taken together, these observations suggest that the pathway sensitive to N-tosyl-L-phenylalanyl chloromethylketone is involved in camptothecin-induced oligonucleosome-sized DNA fragmentation. Furthermore, inhibition of this pathway had no effect on caspase-3-like activation and on the occurrence of high molecular weight DNA fragmentation.

Apoptosis↗
PubMed1997

Detection by denaturing gradient gel electrophoresis of an Arg1689Cys mutation in a Chinese patient with mild hemophilia A.

OBJECTIVE: To detect gene defects of factor VIII (F VIII) in Chinese hemophilia A patients. METHODS: 3' end of exon 14 of F VIII gene from a mild hemophilia A patient of Chinese origin was amplified by polymerase chain reaction (PCR) and identified mutations by denaturing gradient gel electrophoresis (DGGE) combining with direct sequencing. RESULTS: An upward shift band was detected by DGGE in W381. Direct sequencing demonstrated a C to T transition resulting in substitution of Arg1689Cys within a thrombin activation site of mature F VIII protein, which created a unique a thrombin activation site of mature F VIII protein, which created a unique PstI site in amplified fragment of F VIII. CONCLUSIONS: The association of PCR and DGGE can detect a single base substitution; the Arg1689Cys mutation that inhibited activation of F VIII by thrombin is a molecular defect associated with hemophilia A in W381.

Adolescent↗
PubMed1996

[Drug-induced taste disorders].

Taste disorders may have diverse uncomfortable consequences such as reduced quality of life, weight loss and possibly professional disability. The sense of taste depends on many factors. Thus various conditions may cause taste disorders, drugs being one of them. The list of drugs being able to cause taste disorders as adverse drug reaction is long and there are many such cases reported to the Swiss Drug Monitoring Center (SANZ). The possibility of an unwanted side effect should be taken into account if a patient complains about taste disorders, such as reduced or changed sense of taste.

Adult↗
PubMed1996

Presence of autoantibodies to interleukin-8 or neutrophil-activating peptide-2 in patients with heparin-associated thrombocytopenia.

Eighty-seven patients with heparin-associated thrombocytopenia (HAT) showed either a positive heparin platelet aggregometry test result and/or the presence of antibodies to heparin-platelet factor 4 (H-PF4) complexes by enzyme-linked immunosorbent assay (ELISA). Fifteen of these patients lacked antibodies to H-PF4, and plasma from these patients was analyzed for the presence of antibodies to PF4-related chemokines, Neutrophil-activating peptide-2 (NAP-2) and interleukin-8 (IL-8). Of these 15 patients, 6 showed antibodies to IL-8 and 3 to the platelet basic protein (PBP)-derived protein, NAP-2. Antibodies to IL-8 and NAP-2 were not observed in control patients (n = 38), patients with HAT and H-PF4 autoantibodies (n = 72), patients with autoimmune diseases (n = 21), or patients with non-HAT thrombocytopenia (n = 30). Five of these nine patients with anti-IL-8 or anti-NAP-2 developed thrombosis during heparin treatment, which is not statistically different from the patients with H-PF4 antibodies. The existence of autoantibodies to IL-8 and NAP-2 in HAT patients highlights the significance of chemokines in the pathogenesis of HAT. The contribution of heparin in vitro was minimal in patients with anti-IL-8 and anti-NAP-2 antibodies, suggesting a biologic difference from the majority of patients with HAT and anti-PF4 antibodies. It may be that antibodies to IL-8 and NAP-2 have weaker affinity for heparin and that the ELISA system may not reflect in vivo heparin-chemokine complex formation. Alternatively, antichemokine autoantibodies may predate heparin exposure, and the role of heparin in initiating HAT may be to mobilize the chemokines and to target them to platelets, neutrophils, or endothelial cells. Subsequent chemokine-binding autoantibodies then lead to cell activation resulting in thrombocytopenia and thrombosis.

Adult↗
PubMed1996

Scott syndrome, characterized by impaired transmembrane migration of procoagulant phosphatidylserine and hemorrhagic complications, is an inherited disorder.

An as yet single family with a bleeding history is shown to present the characteristic lack of membrane expression of procoagulant phospholipids observed in Scott syndrome. Low prothrombin consumption in the serum of the propositus, a 71-year-old woman, and two of her children was the sole abnormal hemostasis parameter. The degree of exposure of procoagulant phospholipids, chiefly phosphatidylserine, was reduced in stimulated platelets, erythrocytes and Epstein-Barr virus-infected B lymphocytes. The data are compatible with homozygous status of the propositus and heterozygous status of her children. Scott syndrome appears to be transmitted as an autosomal recessive trait reflecting the deletion or mutation of a putative outward phosphatidylserine translocase. The detailed knowledge of this transporter could have an impact in membrane physiology.

Aged↗
PubMed1996

Generation of antibodies to heparin-PF4 complexes without thrombocytopenia in patients treated with unfractionated or low-molecular-weight heparin.

The incidence of antibodies to heparin-PF4 complexes (H-PF4) has been evaluated in patients who were under heparin therapy for more than 7 days: 109 patients treated with unfractionated heparin (UH) and 100 patients with low-molecular-weight heparin (LMWH). The presence of antibodies was identified in 17% of the former group and 8% of the latter. In both the UH and the LMWH groups, IgM antibodies were found in all but four patients who showed IgA antibodies. IgG isotypes were only detected in five patients and were consistently associated to either IgM or IgA antibodies. The follow-up of H-PF4 antibodies in 76 patients treated with UH from 1 to > or = 12 days showed a relationship between the incidence of antibodies and the duration of therapy. Despite the presence of anti-H-PF4 antibodies there was no thrombocytopenia (<150 10(9)/L) in the patients. A significant drop of platelets requiring the discontinuation of heparin was observed, however, in three patients, but their platelet count consistently remained >150 10(9)/L. Our study demonstrates that the induction of antibodies to H-PF4 is a frequent phenomenon in patients treated with UH or with LMWH. The absence of thrombocytopenia and of clinical complications in these patients demonstrates that other conditions must be associated with H-PF4 antibodies for inducing type II HIT: optimal concentrations of heparin and PF4 in the blood circulation to allow the formation of macromolecular H-PF4 complexes, presence of activated platelets that present an increased binding of H-PF4 complexes, increased expression of FcgammaRIIA receptors, or presence of their H 131 phenotype. We conclude that the measurement of antibodies to H-PF4 complexes allows the detection of heparin-treated patients at risk of developing type II HIT.

Autoimmune Diseases↗
PubMed1996

Treatment outcome and dose-response relationship in infants younger than 1 year treated for retinoblastoma with primary irradiation.

Thirty-three infants ( < 1 year at diagnosis) were treated for retinoblastoma with primary irradiation at St. Jude Children's Research Hospital (SJCRH) between 1963 and June 1992. Staging of the 44 treated eyes was as follows: Reese-Ellsworth (R-E) Groups I (n = 20), Group II (n = 9), Group III (n = 6), Group IV (n = 2), Group V (n = 7). Irradiation was delivered using either a single anterior field (31 eyes) or lens-sparing techniques (13 eyes). Total doses ranged from 21-45 Gy (median = 36 Gy) in fractions of 150-180 cGy (n = 34) or > 180 cGy (n = 10). One child died of metastatic disease at 42 months. Three patients have developed second malignant neoplasms; two have succumbed at 88 and 125 months post-RB diagnosis; the remaining patients are alive at 6-259 months postdiagnosis (median follow-up = 127 months). Local control with irradiation alone and supplemented cryotherapy given within 2 months (n = 2) was maintained in 29 eyes, with no statistical difference seen for total doses < or = 36 Gy (21/8 eyes) vs. > 36 Gy (8/16). Of 15 eyes that required salvage therapy, tumor control has been maintained in 13. Enucleation was required for four patients, two with recurrent retinoblastoma and one with a phthisical eye. Cataract formation was documented in 23 eyes (87.5%) treated with lens-sparing techniques developed cataract. At last follow-up, 23 of 30 patients tested (77%) had visual acuity of 20/100 or better. This experience confirms early observations in that doses > or = 36 Gy do not appear to improve local control with irradiation alone in infants ( < 365 days) with retinoblastoma.

Cryotherapy↗
PubMed1996

Molecular basis of von Willebrand disease.

von Willebrand disease (vWD), the most common congenital bleeding disorder in man, is related to quantitative and/or qualitative abnormalities of von Willebrand factor (vWF), a protein necessary for platelet-vessel wall interactions and for carrying factor VIII. Distinct abnormalities of vWF are responsible for the three main types of vWD. Types 1 and 3 are defined by a quantitative defect of vWF whereas type 2, comprising subtypes 2A, 2B, 2M and 2N, refers to patients with a qualitative defect of vWF. Recent progress in the molecular biology of vWF has led to the identification of the molecular basis of vWD in a significant number of patients. Type 2A is characterized by a decreased platelet-dependent function of vWF and includes subtypes IIA and IIC. In all the cases of subtype IIA, aa substitutions have been identified in the A2 domain of vWF which contains a proteolytic site. In the rare subtype IIC, some aa substitutions or insertion have been found within the propeptide of vWF. In type 2B, defined by an increased affinity of vWF for platelet GPIb, various aa substitutions or insertions have been localized within the A1 domain containing binding sites for GPIb, collagen, heparin and sulfatides. In type 2N, characterized by a defective binding of vWF to factor VIII, several aa substitutions have been identified within the factor VIII-binding domain in the N-terminal part of vWF. The identification of gene defects is difficult in types 1 and 3 of vWD. Whereas various abnormalities (gross, partial or point deletions, point insertions, nonsense mutations) have been shown to be at the origin of the quantitative vWF defect in type 3, the molecular basis of type 1 is still unknown in most cases. A data base of gene defects in vWD has been recently established. Its updating may contribute to consider a future classification of vWD based on the nature of the gene defect. Furthermore, the characterization of mutations in vWD presents a more fundamental interest in providing further insight into the structure-function relationship and the synthesis of vWF.

Amino Acid Sequence↗
PubMed1996

Impaired IgG-dependent anaphylaxis and Arthus reaction in Fc gamma RIII (CD16) deficient mice.

The family of receptors for IgG (Fc gamma R) plays an essential role in antibody-mediated effector functions of the immune system. However, the specific contribution of each of the Fc gamma R classes to in vivo immune reactions is still unclear. Here, we demonstrate that mice deficient for the ligand-binding alpha chain of Fc gamma RIII lack NK cell-mediated antibody-dependent cytotoxicity and phagocytosis of IgG1-coated particles by macrophages. Strikingly, these mice lack IgG-mediated mast cell degranulation, are resistant to IgG-dependent passive cutaneous anaphylaxis, and exhibit an impaired Arthus reaction. These results indicate a prominent role for Fc gamma RIII in inflammatory and anaphylactic responses, making this receptor a potential target in immunotherapy.

Animals↗
PubMed1996

Pathogenicity of IgA and/or IgM antibodies to heparin-PF4 complexes in patients with heparin-induced thrombocytopenia.

Antibodies to heparin-PF4 (H-PF4) complexes have been tested and isotyped in 38 patients who developed severe heparin-induced thrombocytopenia (type II HIT). All patients had a platelet count <120x10(9)/1 or a reduction of > 30% of the initial value, occurring at least 5d after the onset of heparin. Thrombocytopenia, which rapidly reversed following the withdrawal of heparin, was associated with thrombosis in nine patients. Although IgG isotypes were found in most cases (n=26), the presence of only IgM and/or IgA was observed in 12 patients, including three cases showing a thrombotic complication. Our results indicate that type II HIT may be induced by IgA and /or IgM anti-H-PF4 antibodies even in the absence of IgG isotypes. This finding demonstrates that platelet Fc receptors (FcgammaRII) are not necessarily involved in the pathogenicity of heparin-dependent antibodies and emphasizes the major role of platelet PF4 receptors. The increased expression of the latter following a slight activation by thrombin, and the subsequent binding of IgM and IgA antibodies to H-PF4 on the platelet surface, may directly trigger platelet activation aggregation and thrombosis. Alternatively, thrombocytopenia could be indirectly induced through the mediation of neutrophils, monocytes and lymphocytes which expose receptors for IgA (FcalphaR) or IgM FcmuR). IgM-platelet complexes may also bind and activate complement, leading to platelet activation or destruction. Moreover, the reactivity of the antibodies with glycosaminoglycans-PF4 complexes present on the endothelial surface could also induce endothelial lesions and promote procoagulant activity and predisposition to thrombosis.

Adult↗
PubMed1996

Multiple founder haplotypes of mitochondrial DNA in Amerindians revealed by RFLP and sequencing.

The mitochondrial DNA (mtDNA) of 139 individuals from eight tribes which belong to four linguistic groups of the Brazilian Amazon Region was studied both by RFLP and by sequencing of the D-loop region. RFLP analysis showed that 41 haplotypes (29%) belonged to haplogroup A, 39 (28%) to haplogroup B, 38 (27%) to haplogroup C, 19 (14%) to haplogroup D, and 2 (< 2%) could not be assigned to any of the four haplogroups. Among the 92 individuals analyzed by direct sequencing of the D-loop region, we observed 43 different haplotypes defined by 48 polymorphic points, while one haplotype could not be assigned to any of the clusters previously described. Joint analysis of data obtained by RFLP and by sequencing of mtDNA demonstrated that, regardless of the method of analysis, the mtDNA haplotypes of contemporary Amerindians cluster into four groups, similar to those previously described, even though 7% of the total sample or 12% of the haplotypes have discrepancies between results obtained by RFLP and sequencing. In addition to supporting the prevalence of four major haplogroups among contemporary Amerindians, our data are compatible with multiple founder haplotypes in each haplogroup, based on: i) a high prevalence of unusual haplotypes: ii) presence of multiple polymorphic sites shared by different haplogroups; iii) relative differences in nucleotide diversity based on RFLP or sequencing within the different haplogroups.

Base Sequence↗
PubMed1996

Bacterial gastroenteritis among hospitalized patients in a Danish County, 1991-93.

BACKGROUND: Denmark has in recent years experienced an increase in the number of bacterial gastrointestinal infections. METHODS: We have reviewed patients hospitalized with culture-confirmed bacterial gastroenteritis in Roskilde County during 1991-93. RESULTS: Two hundred and seven patients were included; 68 were children (< 15 years). The microorganism isolated was Salmonella in 61% of the cases, Campylobacter in 20% and Yersinia enterocolitica in 13%. Ninety-three per cent of the patients had diarrhea, 74% had fever (> 38 degrees C), and 66% abdominal pain. Blood in stools was most frequent in patients infected with Campylobacter. Leukocytosis was rare. Twenty-four patients had bacteremia. Reactive arthritis occurred in 4.8%. Three patients died, all infected with zoonotic Salmonella types. Three stool cultures were made for 115 patients, and in 73% all 3 cultures were positive. CONCLUSIONS: Bacterial gastroenteritis requiring hospitalization affects mainly children and young adults. Infections due to zoonotic Salmonella types were more severe than Campylobacter and Y. enterocolitica gastroenteritis. It seems necessary to make at least three stool cultures to secure a bacteriologic diagnosis.

Adolescent↗