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Biomedical subjects

D Meyer

Publications and source records attributed to D Meyer.

At least 235 records · Page 13Linked to original sources

What men say about pregnancy, birth and parenthood.

Fathers' experiences during their transition to parenthood have been less well documented than those of mothers. This study explored the perceptions of three groups of fathers: fathers were asked to complete a questionnaire covering their experiences during their partner's pregnancy, during antenatal preparation programs or during birth. Fathers in all three groups were asked to respond to a follow-up questionnaire about parenthood. Their views are reported.

Adolescent↗

Stabilization of the hydrophilic sphere of iobitridol, a new nonionic iodinated contrast agent.

The chemotoxicity of iodinated contrast agents is essentially related to the spatial accessibilty of lipophilic and polarizable iodine atoms. This accessibility was examined in iobitridol by HPLC and 1H- and 13C-NMR spectroscopy,taking into account both the static distribution of the hydrophilic groups around the triiodinated benzene ring and in particular the dynamic modulation of this distribution. The aim of this latter parameter is to prevent distortion of the hydrophilic sphere of nonionic agents when faced with a hydrophobic environment. Iobitridol is characterized by 2 tertiary carbamoyl substituents whose high rotation barriers (deltaG*353=27.6 kcal for E/Z-rotation and deltaG*345=17.3 kcal for syn/anti-rotation) stabilize the hydrophilic sphere. The 3rd dihydroxylated anilide substituent does not undergo SMILES rearrangement and provides iobitridol with its even hydrophilic distribution. Iobitridol presents remarkable chemical solubility (>140% m/v) and stability. The iobitridol molecule was specifically designed with the aim of stabilizing the hydrophilic sphere around the triiodinated benzene ring, therefore permanently masking access to the iodine atoms. This new concept represents a further step forward towards the synthesis of new iodinated contrast agents which should be totally inert vis-a-vis biological membranes and proteins.

Chromatography, High Pressure Liquid↗

Overexpression of the Xenopus Xl-fli gene during early embryogenesis leads to anomalies in head and heart development and erythroid differentiation.

The product of the Xl-fli gene, a Xenopus laevis transcription factor of the ets family, specifically expressed in several lineage of migratory cells during Xenopus development (Meyer et al., Int. J. Dev. Biol. 39: 909-919, 1995) was overproduced during Xenopus embryogenesis, upon microinjection of a synthetic transcript in the fertilized egg or in the early embryo. This results in anomalies of the antero-posterior and dorso-ventral polarities, and in tissue differentiation, particularly in the eye- and head cartilage development, as well as erythroid differentiation (absence of erythrocyte differentiation in the circulating blood, often accompanied by ectopic localization of mature erythrocytes, leading to important hemangiomas). Cytological examination reveals at gastrulation the existence of abnormal cells separating the different embryonic layers, suggesting modifications of the cellular adhesion properties. The possible involvement of the fli gene in controlling the dissemination of migratory cells is discussed.

Animals↗

[The risk of needle-stick-injuries during abdominal closure].

A randomized study is being presented, which compares closure of laparotomy with 2 different needles (sharp: HR48, blunt: HR48PP = protect point). Handling and glove perforation rate is to be compared. 400 gloves in 100 laparotomies have been tested. Slightly more effort was reported from the surgeon to perforate the fascia with the blunt needle, but there was also a significantly lower perforation rate in the glove of his non-dominant hand. To avoid a contamination during operation the use of blunt needles has to be recommended.

Abdomen↗

Characterization of recombinant von Willebrand factors mutated on cysteine 509 or 695.

The interacting domain of vWF with platelet GPIb has been shown to overlap the large A1 loop formed by the intra-chain disulfide bond linking Cys 509 to Cys 695. In order to further investigate the role of the conformation of this region, we have expressed in COS-7 cells three mutated full-length recombinant vWFs (rvWFs) in which the substitutions Cys509Gly, Cys509Arg or Cys695Gly have been introduced by site-directed mutagenesis. SDS-agarose gel electrophoresis demonstrated an impaired multimerization of the mutants with undetectable high molecular weight multimers and a decrease of the relative amounts of the intermediate sized multimers. Binding analysis showed that rvWFC509G and rvWFC509R did not interact with botrocetin but spontaneously interacted with GPIb; the latter binding remained unchanged in the presence of ristocetin. This indicates that the substitution of Cys509 by Gly or Arg creates a conformation of vWF that increases its binding to GPIb. In contrast, rvWFC695G which did not react with botrocetin was also unable to interact with GPIb even in the presence of ristocetin, indicating that sequences interacting with GPIb are masked and/or disrupted. In conclusion, the substitution of each of the Cys509 and 695 results in mutant proteins which may be "locked" into active or inactive conformations in regard to the binding to platelet GPIb receptor.

Cysteine↗

Comparison of the 5'-flanking sequences of the human and bovine von Willebrand factor-encoding genes reveals alternation of highly homologous domains with species-specific Alu-type repeats.

von Willebrand factor (vWF), a multimeric glycoprotein important for hemostasis, is specifically synthesized in endothelial cells and in platelet precursors (megakaryocytes). Recent studies from two laboratories, including ours, were published regarding the cell-specific transcription of reporter genes controlled by the human (hu) vWF promoter in transfected bovine (bo) endothelial cells and cells of non-endothelial origins. In order to verify that the regulatory domains previously characterized in the 5' region of hu vWF are also present in bo vWF, we have sequenced 1.9 kb upstream from the cap site, plus five exons. The comparison of human and bovine exons two to five shows homology of 83% at the nucleotide (nt) level and 78% at the deduced amino-acid sequence level. The bovine and human exons one, which are non-coding and span 233 and 250 bp, respectively, are only 64% homologous. In the first exon, potentially involved in endothelial-cell-specific transcription, the binding site for factor Sp1 is present in bo vWF, whereas the GATA sequence is replaced by a GACA sequence. The sequence corresponding to the human basal promoter, located between nt -89 and +19, is well conserved with 82% homology. However, the human TAATTA sequence (at nt -32) considered to be a TATA box, is replaced by TCATTA, and the CCAAT element at nt -18 is replaced by CCTGT. Among domains involved in transcription, the negative regulatory domain located 5' from the core promoter is highly conserved. The bovine sequence upstream from the first intron can be aligned with the human sequence up to nt -656 which is located in a polymorphic poly(GT)18-26 sequence. At this site, the bovine DNA contains an insertion of 523 bp which corresponds to a bovine Alu-type art2 repeat of 331 bp flanked by bovine microsatellites. The art2 sequence is an Alu-type repeat in artiodactyls with at least 100,000 copies in the bovine genome. Upstream from this insertion, 368 bp of the bovine sequence can be aligned with the human counterpart up to a 9-bp element which flanks an human Alu repeat which is absent from the bovine DNA. Upstream of the human Alu insertion and a duplicate of the 9-bp element, the two sequences are again homologous.

Amino Acid Sequence↗

Multiple essential functions of neuregulin in development.

Neuregulin (also called NDF, heregulin, GGF and ARIA) is a member of the EGF family which induces growth and differentiation of epithelial, glial and muscle cells in culture. The biological effects of the factor are mediated by tyrosine kinase receptors. Neuregulin can bind directly to erbB3 and erbB4 and receptor heterodimerization allows neuregulin-dependent activation of erbB2 (refs 1, 2, 5). A targeted mutation in mice reveals multiple essential roles of neuregulin in development. Here we show that neuregulin -/- embryos die during embryogenesis and display heart malformations. In addition, Schwann cell precursors and cranial ganglia fail to develop normally. The phenotype demonstrates that in vivo neuregulin acts locally and frequently in a paracrine manner. All cell types affected by the mutation express either erbB3 or erbB4, indicating that either of these tyrosine kinase receptors can be a component in recognition and transmission of essential neuregulin signals.

Animals↗

Liver resections in Auckland; a retrospective review of patients 1986-91.

AIMS: At a time of subspecialisation throughout medical practice we were interested to review the local experience with regards to elective liver resection. METHOD: A retrospective chart review of all patients undergoing elective liver resection in the Auckland region was performed for the period 1986-91. RESULTS: Over this 6 year period, 30 liver resections were performed, by no less than eight general surgeons. We found little standardisation in either the preoperative work up or the performance of surgery. By international standards a high proportion of patients sustained major complications resulting in long hospital stays. CONCLUSION: We would suggest that such cases should be referred to one or two surgeons working in a team, together with interested radiologists, anaesthetists and oncologists. Only in this way will experience be concentrated; standard protocols be defined; new modalities, eg, intraoperative ultrasound, ultrasonic liver dissection be employed, and postoperative morbidity be reduced. This type of practice should prove to be cost-effective.

Adolescent↗

Angiography contrast agents interact with serine proteinases. The molecular structure of the model system elastase/iohexol.

Pancreatic elastase was co-crystallised with iohexol, a tri-iodo benzenic contrast agent used in angiography analyses. The X-ray analysis of the complex reveals the presence of three molecules of iohexol associated with the proteinase with low occupancy factors. Two iohexol molecules are located in and near the active site of the enzyme and provide a model for explaining the inhibition of the hemostatic system, one of the major and inconvenient side effect associated with these chemicals.

Binding Sites↗

Orbital fractures in children.

OBJECTIVE: To determine if the pattern of orbital fractures may be influenced by the changing craniofacial ratio of the growing child, as the orbit is the boundary between the face and the cranium. DESIGN: Retrospective case series of 40 patients between the ages of 1 year and 16 years with orbital fractures. SETTING: The Albany (NY) Medical Center Hospital, a tertiary level 1 trauma center. OUTCOME MEASURES: The sex, age, site, and mechanism of injury, associated injury, and treatment methods for children admitted to the Albany Medical Center Hospital with orbital fractures between July 1986 and June 1992. RESULTS: Fourteen children had fractures of the orbital roof, 10 children had fractures of the orbital floor, 14 children had mixed fractures, and two children had fractures of the medial wall. The mean age (4.8 +/- 3.3 years) of the 14 patients with roof fractures was significantly less than the mean age (12.0 +/- 4.2 years) of the 26 children with other orbital fractures. Logistic regression demonstrated that the age at which the probability of lower orbital fractures exceeds the probability of orbital roof fractures is 7.1 +/- 1.0 years. Orbital roof fractures had a significantly greater likelihood of associated neurocranial injuries. The need for surgical repair was significantly lower among children with roof fractures as well as among children 7 years of age and younger. CONCLUSIONS: Orbital roof fractures are a type of skull fracture that occur primarily in younger children as a consequence of the proportionally larger cranium and the lack of frontal sinus pneumatization. Lower orbital fractures are a type of facial fracture that occur primarily in older children as a consequence of the increased vulnerability of the face due to growth and the pneumatization of the paranasal sinuses.

Adolescent↗

Recombinant hirudin (HBW 023): biological data of ten patients with severe venous thrombo-embolism.

This study reports on the biological data of ten patients with acute venous thrombo-embolism. They were treated for 5 days with continuous intravenous infusion of a fixed dose (0.05 mg/kg/hr) of a recombinant hirudin (r-H HBW 023 Behringwerke, Germany). The plasma level of r-H (HBW 023), assessed by an anti-factor IIa amidolytic activity, was stable after Day 2 and showed considerable individual variations. It correlated with APTT ratio, suggesting that this test is a reliable tool to monitor therapy. In contrast, thrombin time was constantly over 120 sec (control 15 sec) and consequently was not a useful parameter. Prothrombin time showed a slight, but significant, prolongation, which was correlated with the increase of APTT ratio. There was no bleeding time prolongation, platelet count, or ATIII level decrease. Levels of thrombin-antithrombin III complexes, and D-dimers, which were high in all patients on admission, decreased during the course of the treatment but remained abnormal on Day 5, showing an ongoing hemostasis and fibrinolysis activation: this is consistent with the delayed, but only slightly decreased thrombin generation evidenced by thrombin generation test performed on Day 3. These results suggest that thrombin inhibition by rH-hirudin at this dosage is only partial, which allows the generation of traces of thrombin needed for the feed-back thrombin production generated by factor V and VIII activation.

Adult↗

Use of irradiation for therapy of retinoblastoma in children more than 1 year old: the St. Jude Children's Research Hospital experience and review of literature.

Fifteen children (> 1 year old at diagnosis) were treated for retinoblastoma (RB) with primary irradiation at St. Jude Children's Research Hospital between January 1963 and January 1992. Staging of the 19 treated eyes was as follows: Reese-Ellsworth (R-E) Groups I and II, n = 7; Group III, n = 3; Group IV, n = 1; Group V, n = 7; information on one globe is incomplete. Total dosage ranged from 25 to 45 Gy (median = 40 Gy) in fractions of 170-225 cGy delivered 5 x/week (n = 13) or 225-265 cGy delivered 4 x/week (n = 4 eyes) or x 5/week (n = 2 eyes). Treatment techniques included anterior field (n = 11) or lens-sparing technique (n = 8). One patient has died of progressive central nervous system (CNS) disease at 13 months; one patient succumbed to second malignant neoplasm within the irradiated field at 194 months; the remaining 13 patients remain alive from 27 to 301 months (median = 178 months). Local control with irradiation alone has been maintained in 12 eyes. Four eyes with local recurrence were salvaged using cryotherapy or reirradiation. Enucleation was required for three eyes for progressive disease at 4, 7, and 7 months postirradiation. Cataract formation was documented in nine eyes treated with anterior fields and in one patient treated with lens-sparing technique. At last follow-up, 7 patients had visual acuity of 20/100 or better. Radiation dose of 40 Gy appears to be adequate for local control of early stage RB (R-E Groups I-III and VB whose tumors are R-E Groups I-III) in patients > 1 year old. The results of this limited series which has lengthy follow-up is compared with the results of previously published data in an effort to define the benefits and disadvantages of the different treatment techniques which have been reported in the treatment of RB in children > 1 year old.

Cataract↗

Investigation of the thermal stability of Ni/C multilayers by X-ray methods.

Microstructural properties of Ni/C multilayers prepared by PLD (pulsed laser deposition) have been investigated after heat treatment in vacuum at temperatures in the range of 50 degrees C to 500 degrees C. X-ray diffractometry, X-ray reflectometry, fluorescence EXAFS (extended X-ray absorption fine structure) and HREM (high resolution transmission electron microscopy) have been applied to characterize samples in the initial state and after annealing. The multilayer reflectivity remained unchanged or increased at temperatures below 400 degrees C due to sharpening of the interfaces caused by the formation of alpha-nickel and nickel carbide. The reflectivity decreased at temperatures above 400 degrees C because of the fragmentation of the nickel layers. It can be shown, that both chemical and mechanical driving forces are responsible for the observed modifications of the initial specimen state.

Journal Article↗

Factors controlling growth, motility, and morphogenesis of normal and malignant epithelial cells.

Factors that control epithelial growth, motility, and morphogenesis play important roles in malignancy and in normal development. Here we discuss the molecular nature and the function of two types of molecules that control the development and maintenance of epithelia: Components that regulate epithelial cell adhesion; and soluble factors and their receptors that regulate growth, motility, differentiation, and morphogenesis. In development, the establishment of epithelial cell characteristics and organization is crucially dependent on cell adhesion and the formation of functional adherens junctions. The integrity of adherens junctions is frequently disturbed late in tumor progression, and the resulting loss of epithelial characteristics correlates with the metastatic potential of carcinoma cells. Various soluble factors that induce epithelial growth, motility, or differentiation in cell culture, function via tyrosine kinase receptors. We concentrate here on receptors that are expressed exclusively or predominantly on epithelia, and on ligands that are derived from the mesenchyme. In development, these receptors and their ligands function in mesenchymal-epithelial interactions, which are known to govern growth, morphogenesis, and differentiation of epithelia. During tumor development, mutations or overexpression of the receptors are frequently observed; these alterations contribute to the development and progression of carcinomas.

Animals↗

Intraocular pressure response to combined phacoemulsification and trabeculotomy ab externo versus phacoemulsification alone in primary open-angle glaucoma.

We investigated trabeculotomy ab externo as a means of optimizing intraocular pressure (IOP) control in glaucoma patients having phacoemulsification and implantation of an intraocular lens (IOL). A prospective, randomized, controlled study was performed to evaluate the effect on IOP and the incidence of complications associated with combined phacoemulsification and trabeculotomy ab externo. The study group had the combined procedure, while the control group had only phacoemulsification with IOL implantation. A total of 106 patients were randomized, and the IOP for each group was compared at 3, 6, 12, and 24 months. At two years, the mean IOP reduction was 6.1 mm Hg in the study group and 3.8 mm Hg in the control group (P = .001). There were no complications in the control group. Two complications (2/53 or 3.8%) occurred in the study group: a small tear in Descemet's membrane and a postoperative microhyphema. There was no increase in medication in either the study or control group. Combined phacoemulsification and trabeculotomy ab externo represents an option to lower IOP and potentially reduce the need for pressure-lowering medications in patients with primary open-angle glaucoma and visually significant cataracts.

Aged↗

Stabilization of the hydrophilic sphere of iobitridol, an iodinated contrast agent, as revealed by experimental and computational investigations.

PURPOSE: The regular distribution in space and the stability in time of the hydrophilic sphere surrounding iobitridol were investigated. This is a novel yet important concept in the design of polyiodinated contrast agents since such a sphere is meant to hide their hydrophobic core and thus prevent hydrophobic interactions with biomacromolecules and hence chemotoxicity. METHODS: The methods used were experimental (HPLC, 1H- and 13C-NMR spectroscopy) and computational (calculation of conformational behavior and molecular electrostatic potentials). RESULTS: Iobitridol exists as a mixture of stereoisomers due to hindered rotation around several bonds. High-temperature molecular dynamics established the existence between 0 and 15 kcal/mol of 238 conformers belonging to 14 classes. Most of these conformers have an inaccessible hydrophobic core, and variable temperature molecular dynamics confirmed that the hydrophilic sphere around iobitridol is stable against external disruption. CONCLUSIONS: This study has demonstrated that iobitridol fulfils the physicochemical and structural criteria believed to render a polyiodinated contrast agent inert toward interacting with biomacromolecules.

Chemical Phenomena↗