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D Meyer

Publications and source records attributed to D Meyer.

At least 253 records · Page 14Linked to original sources
PubMed1995

Sequential requirement of hepatocyte growth factor and neuregulin in the morphogenesis and differentiation of the mammary gland.

We have examined the role of two mesenchymal ligands of epithelial tyrosine kinase receptors in mouse mammary gland morphogenesis. In organ cultures of mammary glands, hepatocyte growth factor (HGF, scatter factor) promoted branching of the ductal trees but inhibited the production of secretory proteins. Neuregulin (NRG, neu differentiation factor) stimulated lobulo-alveolar budding and the production of milk proteins. These functional effects are paralleled by the expression of the two factors in vivo: HGF is produced in mesenchymal cells during ductal branching in the virgin animal; NRG is expressed in the mesenchyme during lobulo-alveolar development at pregnancy. The receptors of HGF and NRG (c-met, c-erbB3, and c-erbB4), which are expressed in the epithelial cells, are not regulated. In organ culture, branching morphogenesis and lobulo-alveolar differentiation of the mammary gland could be abolished by blocking expression of endogenous HGF and NRG by the respective antisense oligonucleotides; in antisense oligonucleotide-treated glands, morphogenesis could again be induced by the addition of recombinant HGF and NRG. We thus show that two major postnatal morphogenic periods of mammary gland development are dependent on sequential mesenchymal-epithelial interactions mediated by HGF and NRG.

Animals↗
PubMed1995

Escherichia coli lacZ strains engineered for detection of frameshift mutations induced by aromatic amines and nitroaromatic compounds.

Escherichia coli lacZ strains CC107-CC111, which detect specific frameshift mutations, were used to study the mutational specificities of 2-nitro-3-methylimidazo[4,5-f] quinoline (NO2-IQ) and rat hepatic S9-activated 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). New constructs were made in which UvrABC-dependent excision repair was eliminated (strains DJ3107-DJ3111), followed by introduction of plasmid pYG219 conferring acetyl CoA:arylamine N-acetyltransferase/acetyl CoA:arylhydroxylamine O-acetyltransferase (NAT/OAT) activity (strains DJ3207-DJ3211). Sensitivity to mutagens was greatly enhanced. The mutational specificity of NO2-IQ was identical to that of the corresponding amine, IQ. The most prominent mutations caused by the two compounds were -2(CGGC) and 1(CG) frameshifts. +1(AT) Frameshifts play a minor role in the pattern of mutational specificity. Induction of all three mutations was similarly influenced by NAT/OAT activation and UvrABC-dependent excision repair. These new tester strains provide an effective tool for the study of aromatic amine mutational specificity and the influences of excision repair and NAT/OAT activation.

Acetyltransferases↗
PubMed1995

Cyclic adenosine monophosphate-dependent mechanisms induce von Willebrand factor expression in the Dami megakaryoblastic cell line.

It has been proposed that cyclic adenosine monophosphate (cAMP) is involved in the differentiation of several cell types and this study analysed whether von Willebrand factor (vWf) synthesis, which is a marker of the megakaryocyte maturation of these cells, would be enhanced by agents acting on cAMP formation. Different compounds known to stimulate cAMP accumulation in cells were used: dibutyryl cAMP (db-cAMP), isobutyl-methylxanthine (IBMX) or pentoxifylline (PTX) and forskolin. Treatments with db-cAMP or IBMX (10-1,000 microM) induced a dose-dependent increase in vWf synthesis. Associations of IBMX with forskolin produced a synergistic enhancement in vWf synthesis. PTX alone did not enhance vWf synthesis but a latent effect was revealed in the presence of forskolin or db-cAMP. The increase in vWf mRNA shown by Northern blot analysis demonstrates that the protein synthesis correlates with the transcript expression after db-cAMP or IBMX treatments. vWf synthesis paralleled the accumulation of cAMP in the cells. Moreover vWf expression induced by combination of IBMX with forskolin was associated with a moderate increase in the percentage of GPIIb/IIIa positive cells and in the ploidy level related to an important inhibition of cell growth. These data provide evidence that agents acting on cAMP metabolism induce vWf synthesis in the Dami megakaryoblastic cells.

1-Methyl-3-isobutylxanthine↗
PubMed1995

A monoclonal antibody (B724) to von Willebrand factor recognizing an epitope within the A1 disulphide loop (Cys509-Cys695) discriminates between type 2A and type 2B von Willebrand disease.

Monoclonal antibody (MoAb) B724 to von Willebrand factor (vWF) completely inhibits its interaction with heparin, sulphatides and botrocetin and consequently botrocetin-induced binding of vWF to platelets. MoAb B724 has no effect on the binding of vWF to collagen or to ristocetin-treated platelets nor on vWF-dependent platelet aggregation induced with ristocetin and asialo-vWF-mediated platelet aggregation. MoAb B724 preferentially recognizes a conformation of native vWF, in solution, or immobilized through a coated antibody. It exhibits a markedly lower affinity for vWF immobilized onto collagen or plastic surfaces. Using proteolytic fragments of vWF, B724 epitope was localized within the 512-673 sequence of the A1 disulphide loop of vWF, MoAb B724 was used as second antibody in a two-site ELISA to test a series of patients with type 1, 2A, 2B and 2N vWD or haemophilia A and recombinant wild type or mutated vWFs. Results were compared with those obtained by control ELISAs performed using polyclonal antibodies. Using MoAb B724, strikingly lower levels of vWFAg were observed in plasma from most patients with type 2B vWD, and in seven out of the eight rvWF mutated close to or within the A1 disulphide loop. Therefore MoAb B724, which interferes with this loop involved in the function of vWF, appears to be a useful tool for rapid screening of conformational changes in this region.

Antibodies, Monoclonal↗
PubMed1995

Characteristics of Actinobacillus actinomycetemcomitans invasion of and adhesion to cultured epithelial cells.

Actinobacillus actinomycetemcomitans (A.a.) is highly implicated in periodontitis. We have developed several in vitro models using the KB oral cell line to examine A.a.-epithelial cell interactions. In support of the use of KB cell line model systems is our finding that A.a. invaded KB and primary gingival cells to the same extent. Invasion is an active event which requires new protein synthesis by both KB and A.a. Like many other intracellular parasites, A.a. invade by receptor-mediated endocytosis. We observed that internalized A.a. were surrounded by foci of actin which had been transported from the periphery of the KB cell. Adhesion of A.a. to KB cells occurred rapidly and stimulated the formation of microvilli. Adhesion is affected by both host factors (saliva, serum, [NaCl]) and culture conditions. Multiple determinants [fimbriae, outer membrane proteins, vesicles, and/or an extracellular amorphous material (ExAmMat)] which are either associated with the A.a. surface or are released into the milieu are involved. We determined that ExAmMat can convey adhesiveness to weakly adherent A.a. and to at least one other oral species (Streptococcus parasanguis).

Adhesins, Bacterial↗
PubMed1995

Second malignant neoplasms in children with retinoblastoma: the St. Jude Children's Research Hospital experience.

A retrospective review of 172 children with primary diagnosis of retinoblastoma (RB) was completed at St. Jude Children's Research Hospital to evaluate the incidence of second malignant neoplasm (SMN) development. Sixty-five patients presented with bilateral RB and 107 with unilateral RB. During follow-up, which ranged from 6 to 340 months (median = 170 months), 6 children (3.5%) developed SMN. All patients who developed SMN presented with bilateral disease (n = 5) or asynchronous bilateral disease (n = 1); two patients had a family history of RB. All had received irradiation. Four patients developed osteogenic sarcoma within this irradiated volume, one developed a basal cell carcinoma in the temporal region (within the irradiation field), and one was diagnosed with a lower extremity Ewing's sarcoma. Time to development of SMN ranged from 125 to 194 months post-irradiation. Initial irradiation total dose ranged between 32 and 45.76 Gy. Three patients were treated with anterior field irradiation and three received lens-sparing techniques (anterior/lateral n = 2, lateral n = 1). At last follow-up, 4/6 patients had died of SMN. The crude incidence is 3.5% with an estimation of risk using the density method of 24% at 20 years for SMN development. The specifics of the treatment associated with these second malignancies and the possible reasons for the reported incidence of SMN will be discussed.

Child↗
PubMed1995

Asynchronous bilateral retinoblastoma: the St. Jude Children's Research Hospital experience.

Between May 1962 and July 1993, 172 children presented at the St. Jude Children's Research Hospital for evaluation and/or treatment of retinoblastoma (RB). Of these, 65 presented with bilateral disease, while 107 had unilateral tumors. Of these 107 patients, nine subsequently developed RB in the unaffected eye. Initial age at diagnosis of these nine patients ranged from 3 weeks to 24 months (median = 2 months); five of the nine had a family history of RB at the time of initial diagnosis and one patient, without a family history of RB, presented with unilateral multiple tumors indicating inheritance of a germinal mutation and increased risk of RB development in the companion eye. Time to development of companion eye RB was 1-61 months postinitial diagnosis. Treatment of the initial eye included enucleation (n = 4), chemotherapy (n = 3), irradiation (n = 7), or a combination of these three modalities. Reese-Ellsworth grouping of the companion eye disease included I A (n = 7), III A (n = 1), and IV A (n = 1). Treatment of the second affected eye included irradiation in seven patients, cryotherapy in four, and chemotherapy in three. No companion eye has required enucleation to date. At last followup, 14/18 eyes remain intact. There have been no cases of metastatic dissemination; however, one patient has developed a second malignant neoplasm outside the field of irradiation. Eight of the nine patients remain alive. This experience reinforces the need for close follow-up of patients diagnosed with unilateral RB, especially those with a family history of RB and those with unilateral multiple tumors.

Child, Preschool↗
PubMed1995

[Combined liver-islet transplantation after epigastric exenteration in carcinoma of Vater's ampulla].

A 44 year old female underwent an upper abdominal exenteration because of an adenocarcinoma of the pancreas with liver metastases (T1 N1 M1). Reconstruction was performed by orthotopic liver transplantation and intraportal islet transplantation. Due to initial non function of the first liver graft, a second liver transplantation was performed. Thereafter, the patient received 375,000 islet equivalents of the primary liver donor in addition to 295,400 islet equivalents of another donor. Six months postoperatively, the patient is off insulin except irregular injections of 4-6 units of insulin to protect her from hyperglycemia after lunch. CT scans of the liver do not show any signs of tumor recurrence. Upper abdominal exenteration with consecutive islet transplantation offers a good method of reconstruction after radical surgery in the upper abdomen. The oncological aspects of the procedure have to be further investigated.

Adenocarcinoma↗
PubMed1995

[Is ion-selective measurement of the liver surface for detection of cell damage suitable?--A study of the rat liver transplantation model].

UNLABELLED: Aim of the study is to detect a reperfusion injury in rat liver transplantation by the Ion-selective Surface-Measurement (OMS). METHODS: Lewis rats served as models for 30 liver transplantations with 1, 6 or 12 hrs of cold ischemia respectively. Directly before, during and after transplantation potassium- and hydrogen-concentrations were measured with the OMS and compared to transaminase values on day 1, 3 and 7 as well as to biopsies on day 3. RESULTS: Transaminase values and histology show ischemic cell injuries correlating to the length of ischemia, whereas potassium- and hydrogen-concentrations on the organ surface do not. CONCLUSIONS: Ischemic cell injury in the rat liver cannot be detected by the Ion-selective Measurement.

Acid-Base Equilibrium↗
PubMed1995

Antibodies to macromolecular platelet factor 4-heparin complexes in heparin-induced thrombocytopenia: a study of 44 cases.

As heparin-PF4 (H-PF4) complexes are the target for antibodies associated to heparin-induced thrombocytopenia (HIT), an ELISA has been developed and optimised for testing antibodies binding to H-PF4. This test was consistently negative in 50 healthy subjects (A492 < 0.3) and 35 patients with other causes of thrombocytopenia (A492 < 0.5). In contrast, 43 out of 44 HIT patients showed antibodies to H-PF4 (A492 = 1.70 +/- 0.81) including 5 patients with a negative platelet aggregation test. In one patient with HIT, antibodies to H-PF4 were already present at day 7, whereas platelet counts dropped < or = 100 x 10(9)/l only at days 11-12. Surprisingly, among 41 patients under heparin for > 7 days, 5 showed antibodies to H-PF4, without HIT. These findings underline the major interest of this ELISA for the early diagnosis of HIT. We also showed that LMWH as well as other sulphated polysaccharides can bind to HIT antibodies in the presence of PF4 and that their reactivity is dependent on the molecular weight and the sulphation grade. The mechanism for HIT involves platelet PF4 receptors which bind the macromolecular H-PF4 complexes formed in the presence of a well defined heparin/PF4 ratio.

Adolescent↗
PubMed1995

[The behavior modifying influence of malpractice--effects on choice of technology].

This article analyses the legal concepts of the professional indemnity of the physician in respect of damage caused by him due to fault or negligence, underlining the problem of legal uncertainty connected therewith. Pointers to the possible financial risk involved are given in a review dealing with the probability of damage, costs that may be incurred by such damage, and professional indemnity insurance premiums. Attention is then directed at the influence these factors can exercise on the behaviour and attitude of the physician in respect of performance of medical services and care and on the choice of treatment methods. The defensive type of medical care and the therapeutic gap are mentioned as examples of such changes.

Attitude of Health Personnel↗
PubMed1995

Structure-function relationship of the A1 domain of von Willebrand factor.

von Willebrand factor (vWF) is a multimeric glycoprotein composed of multiple homologous domains. The A1 domain contains a remarkably large disulfide loop of 185 amino acids (Cys 509-695) which plays a key role in promoting platelet adhesion to the subendothelium. Following the initial binding of the A1 domain to the subendothelium, a conformational change occurs which allows its binding to platelet GPIb. In an attempt to further understand the structure-function relationship of the A1 domain, we analyzed 1) the functional properties of recombinant vWF mutated on either Cys 509 or 695 and 2) the reactivity of a monoclonal antibody (MoAb B724) with vWF conformations interacting with GPIb. Our data underline the crucial role of the 509-695 disulfide bond in the binding of vWF to GPIb and discriminate the specificity of each Cys in this binding. They also indicate that two different conformations of the A1 loop, with high or low affinity for MoAb B724, allow the exposure of its GPIb-binding site. Since the low affinity conformation is observed in type 2B vWF, MoAb B724 appears as a useful tool to probe this type of von Willebrand disease (vWD).

Antibodies, Monoclonal↗
PubMed1995

Whole-mount in situ hybridization reveals the expression of the Xl-Fli gene in several lineages of migrating cells in Xenopus embryos.

The expression of the Xl-Fli gene, which belongs to the ets family of transcription factors, was studied by whole-mount in situ hybridization during Xenopus embryogenesis. Digoxigenin-labeled antisense RNA probes were synthesized by in vitro transcription and used in the hybridization reaction. In addition to expression in territories invaded by neural crest cells reported earlier (Meyer et al., 1993), we observed Xl-Fli gene expression in a number of regions affected by important cellular migrations and/or epithelium<==>mesenchyme transitions: in the endothelial cells of the heart, in blood vessels, along the pronephric duct migration pathway and at the level of hypophysis. The possibility that the FLI protein is involved in the expression of guidance cues and/or modification of the cellular adhesion properties is discussed. A screening of a promoter library with a consensus sequence, bound by the FLI protein with a high affinity, revealed the presence of putative FLI response elements in a number of genes encoding adhesion molecules or components of the extra-cellular matrix.

Animals↗
PubMed1994

Use of a rapid assay of subforms of creatine kinase MB to diagnose or rule out acute myocardial infarction.

BACKGROUND: Ruling out myocardial infarction in patients coming to the emergency room with chest pain is hindered by the lack of a specific early diagnostic marker. Less than 30 percent of patients admitted to coronary care units have infarction, resulting in substantial unnecessary expenditures. We developed a rapid assay of the subforms of creatine kinase MB (CK-MB) and prospectively analyzed its sensitivity and specificity in diagnosing myocardial infarction in the first six hours after the onset of chest pain. METHODS: In 1110 consecutive patients who came to the emergency room with chest pain, blood samples were collected every 30 to 60 minutes until at least 6 hours after the onset of symptoms; in patients who were then admitted to the hospital, samples were collected every 4 hours for up to 48 hours. The samples were analyzed for CK-MB subforms, and the diagnosis of myocardial infarction was confirmed by conventional CK-MB analysis. RESULTS: Of the 1110 patients evaluated, 121 had myocardial infarction. The sensitivity of the assay of CK-MB subforms to detect myocardial infarction in the first six hours after the onset of symptoms was 95.7 per cent, as compared with only 48 percent for the conventional CK-MB assay; the specificity was 93.9 percent among patients hospitalized without myocardial infarction and 96.2 percent among those sent home. Among the patients with myocardial infarction, definitive results of the subform assay were available a mean (+/- SD) of 1.22 +/- 1.17 hours after their arrival in the emergency room. CONCLUSIONS: The assay of CK-MB subforms reliably detected myocardial infarction within the first six hours after the onset of symptoms, and its use could reduce admission to the coronary care unit by 50 to 70 percent, thereby reducing costs.

Biomarkers↗
PubMed1994

Influence of mutations and size of multimers in type II von Willebrand disease upon the function of von Willebrand factor.

We compared the properties of plasma von Willebrand factor (vWF) from normal individuals and from two patients with type IIA (Glu875Lys) and type IIB (duplication of Met 540) von Willebrand disease (vWD) with the corresponding fully multimerized recombinant proteins. We included cryosupernatant from normal human plasma and type IIA plasma (Cys509Arg). Functions of vWF were analyzed by binding assays to platelets in the presence of ristocetin or botrocetin. Parameters of binding (number of binding sites per vWF subunit, and dissociation constant Kd) were quantitatively estimated from the binding isotherms of 125I-botrocetin or glycocalicin to vWF, independently of the size of the multimers. We found that ristocetin- or botrocetin-induced binding to platelets was correlated in all cases with the size of vWF multimers. In the absence of inducer, only type IIB rvWF Met-Met540 spontaneously bound to platelets. No significant difference of binding of purified botrocetin to vWF was found between normal and patients' plasma, or between wild-type rvWF (rvWF-WT) and rvWF-Lys875. In contrast, affinity of botrocetin for type IIB rvWF Met-Met540 was decreased. Botrocetin-induced binding of glycocalicin to vWF from all plasma and cryosupernatant was similar. Compared with rvWF-WT, binding of glycocalicin to rvWF-Lys875 was normal. In contrast, the affinity for type IIB rvWF Met-Met540 was 10-fold greater. Thus, our data suggest that, in the patients tested, the abnormal IIA phenotype results from the lack of large-sized multimers and is independent of the point mutations. In contrast, the type IIB mutation is directly involved by providing a conformation to the vWF subunits that allows the high molecular weight multimers to spontaneously interact with platelet glycoprotein Ib.

Animals↗
PubMed1994

Distinct isoforms of neuregulin are expressed in mesenchymal and neuronal cells during mouse development.

Neuregulin, the putative ligand of the c-neu receptor tyrosine kinase, can induce differentiation or growth of epithelia and other cells. To gain insight into the biological role of this factor, we have analyzed the expression of neuregulin during mouse embryogenesis and in the perinatal animal by a combination of in situ hybridization and RNase protection experiments. We identify sites of expression that correspond to mesenchymal cells of various parenchymal organs. Our finding implies a function of neuregulin as a mesenchymal factor that acts on epithelia. The mesenchymal expression of neuregulin could thus provide a molecular basis for the biological phenomenon of mesenchymal-epithelial interactions. It also has implications on the molecular mechanism by which amplification of c-neu can affect tumor progression of carcinomas. In addition, neuregulin expression is found in neuronal cells during development. We show by RNase protection experiments that distinct isoforms of neuregulin are expressed in the brain. Therefore, our data indicate in vivo a dual role for neuregulin as mesenchymal and neuronal factor.

Animals↗
PubMed1994

Discrepancy between IIA phenotype and IIB genotype in a patient with a variant of von Willebrand disease.

Type IIA and IIB von Willebrand disease (vWD) result from qualitative abnormalities of von Willebrand factor (vWF) characterized by an absence in plasma of high molecular weight vWF multimers and an abnormal reactivity of vWF towards platelet glycoprotein (GP) Ib, which is decreased in type IIA and increased in type IIB. In this report, we describe the case of a patient having a IIA vWD phenotype associated with an intermittent thrombocytopenia atypical in this subtype but observed in type IIB vWD. The patient plasma vWF showed an absence of high molecular weight and intermediate multimers and had a decreased binding capacity to GPIb. The affinity of botrocetin was normal for plasma vWF from the propositus. Analysis of the propositus vWF gene showed the presence of a substitution Val 551 to Phe of the mature vWF subunit. This mutation is localized within a 509-695 disulphide loop of the vWF that plays an important role in the binding to GPIb and is where most of the molecular defects described so far were associated with type-IIB vWD. We have reproduced the Val 551 Phe substitution onto the vWF cDNA, expressed it in COS-7 cells, and performed structural and functional analysis of the mutant recombinant protein (rvWFPhe 551). The rvWFPhe 551 had a normal multimeric structure and showed the capacity to spontaneously interact with GPIb. Botrocetin had a decreased affinity for rvWFPhe 551. In conclusion, the Val 551 Phe mutation modifies the affinity of vWF for platelet GPIb, as does a type IIB mutation, and may be responsible for the thrombocytopenia of the patient and the clearance of the high molecular weight and intermediate-sized multimers of vWF from the plasma. The study of the rvWFPhe 551 has confirmed the discrepancy between the IIA phenotype and the IIB genotype of the patient.

Adolescent↗