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M Moser

Publications and source records attributed to M Moser.

At least 37 records · Page 2Linked to original sources
PubMed2003

Developmental competence of oocytes showing increased cytoplasmic viscosity.

BACKGROUND: The objective of the study was to investigate the developmental fate of oocytes with increased cytoplasmic viscosity as assessed by the persistence of the injection funnel after withdrawal of the ICSI pipette. METHODS: For this purpose, 1008 oocytes showing a characteristic injection funnel during ICSI were subdivided into two groups according to the oocyte's ability to restore its spherical shape within 2-3 min after ICSI. Fertilization and further development was evaluated in both groups. In addition, implantation and pregnancy rates were analysed. RESULTS: In the funnel positive cohort (group 1) significantly fewer oocytes degenerated after injection (P < 0.01) compared with oocytes without persistent funnel (group 2). However, at zygote stage, presence of a halo (P < 0.05) and a optimal pronuclear pattern 0 (P < 0.01) was increased in group 2. In addition, significantly fewer poor quality embryos were found in this group (P < 0.01). The number of good quality blastocysts but not blastocyst formation was increased in group 2 (P < 0.05). This resulted in an increased clinical pregnancy rate if embryos which derived exclusively from funnel negative oocytes were transferred (P < 0.05). CONCLUSIONS: Our data suggest that cytoplasm of higher viscosity delays development up to cleavage stage and impairs optimal development. Injection funnel persistence was found to be a negative prognostic marker of preimplantation development.

Blastocyst↗
PubMed2003

Presence, but not type or degree of extension, of a cytoplasmic halo has a significant influence on preimplantation development and implantation behaviour.

BACKGROUND: Since there is considerable disagreement in grading cytoplasmic haloes, this prospective study was set up to evaluate if certain subtypes of haloes are related to further development. METHODS: Out of a total of 152 patients, 713 zygotes could be checked for the formation of a halo. Where present, haloes were subdivided into concentric (symmetric) and polar (asymmetric) types. In addition, each halo was measured accurately to see if the extension of the halo might influence further development. In parallel, pronuclear patterns were checked. RESULTS: Halo-positive zygotes did not differ from halo-negative ones in terms of embryo quality and blastocyst formation rate. However, quality of blastocysts (assessed by their inner cell mass consistency) was significantly increased (P < 0.001) if a halo appeared at zygote stage. This phenomenon was not related to type of halo or degree of halo. In terms of pronuclear pattern, pattern 0 (0A, 0B) led to significantly more blastocysts (P < 0.001) of better quality (P = 0.002) compared with patterns 1-5. A stepwise logistic regression showed no relationship between different halo types and pronuclear pattern 0. CONCLUSIONS: The present study indicates that any halo has a positive prognostic value on blastocyst quality, irrespective of the fact that it is light or extreme, polar or concentric. In addition, the developmental advantage of pattern 0 is confirmed.

Adult↗
PubMed2002

Signal recognition particle-dependent protein targeting, universal to all kingdoms of life.

The signal recognition particle (SRP) and its membrane-bound receptor represent a ubiquitous protein-targeting device utilized by organisms as different as bacteria and humans, archaea and plants. The unifying concept of SRP-dependent protein targeting is that SRP binds to signal sequences of newly synthesized proteins as they emerge from the ribosome. In eukaryotes this interaction arrests or retards translation elongation until SRP targets the ribosome-nascent chain complexes via the SRP receptor to the translocation channel. Such channels are present in the endoplasmic reticulum of eukaryotic cells, the thylakoids of chloroplasts, or the plasma membrane of prokaryotes. The minimal functional unit of SRP consists of a signal sequence-recognizing protein and a small RNA. The as yet most complex version is the mammalian SRP whose RNA, together with six proteinaceous subunits, undergo an intricate assembly process. The preferential substrates of SRP possess especially hydrophobic signal sequences. Interactions between SRP and its receptor, the ribosome, the signal sequence, and the target membrane are regulated by GTP hydrolysis. SRP-dependent protein targeting in bacteria and chloroplasts slightly deviate from the canonical mechanism found in eukaryotes. Pro- and eukaryotic cells harbour regulatory mechanisms to prevent a malfunction of the SRP pathway.

Animals↗
PubMed2002

[Otorhinolaryngologic diseases and flying].

Physiological and pathological aspects of pressure changes, noise, acceleration, variation of temperature, low humidity, stress and time differences in flight passengers and aircrew are discussed. Typical ear, nose, and throat clinic (ENT)-cases such as tubal function disturbances, barotrauma, hypacusis, sudden hearing loss, tinnitus, acute and chronic middle ear diseases, post ear surgery conditions, hearing aids, vertigo and motion sickness are described. The influence on flying of acute and chronic affections of the paranasal sinuses, nasal septal deviation and allergy are listed. The problem of transport of ENT-incapacitated passengers in commercial aircrafts and ambulance jets are dealt with.

Aerospace Medicine↗
PubMed2002

Prospective hatching of embryos developed from oocytes exhibiting difficult oolemma penetration during ICSI.

BACKGROUND: The hormonal milieu during ovarian stimulation is known to affect oolemma behaviour as well as zona pellucida thickness and structure. This led us to investigate whether a special subgroup of patients with oocytes where penetration of the oolemma is difficult during ICSI may benefit from assisted hatching. METHODS: A total of 77 couples (mean age: 32.9 +/- 4.6 years; range: 22-38) had oocytes that could hardly be penetrated by the ICSI pipette. Nineteen patients underwent two ICSI cycles, giving a total number of 96 cycles, which were randomly split into either the study group (n = 52) or the non-hatching group (n = 44). Hatching was done using a non-contact 1.48 mm wavelength diode laser. Implantation and pregnancy rates were recorded. RESULTS: The pregnancy rate was 36.6% (19/52) in the study group and 13.6% (6/44) in the non-hatching group (P < 0.05). In addition, a higher number (P < 0.05) of embryos implanted in the study group (23/106; 21.7%) than in the non-hatching group (9/92; 9.8%). CONCLUSIONS: Once oolema penetration during ICSI has proven difficult, prospective hatching of embryos considered for transfer may increase their implantation behaviour.

Adult↗
PubMed2002

First polar body morphology and blastocyst formation rate in ICSI patients.

BACKGROUND: It may be beneficial to identify, at a very early stage of development, concepti that will result in viable blastocysts by using a non-invasive technique. METHODS: Homogeneous groups in terms of first polar body (PB) morphology were analysed with regard to fertilization, embryo quality and blastocyst formation. The strategy was to transfer a maximum of two blastocysts with an adequate inner cell mass deriving from oocytes with identical first PBs in order to obtain information about the actual implantation potential. RESULTS: A significant relationship between first PB morphology and embryo quality was found. Fragmentation after 2 days was increased in embryos derived from oocytes with fragmented first PBs (P < 0.05) in comparison with those derived from oocytes with intact PBs. No similar correlation could be demonstrated for fertilization rate. Embryos in the intact first PB group showed an increased rate of blastocyst formation as compared with the fragmented first PB group (P < 0.05). In addition, a significant difference in implantation rate (48.6 versus 22.0%; P < 0.025) and ongoing pregnancy rate (68.4 versus 34.8%; P < 0.05) was observed for the intact versus fragmented groups respectively. CONCLUSION: In conclusion, the current study provides further evidence that preselection at a very early stage may be helpful in identifying a subgroup of preimplantation embryos with a good prognosis to form blastocysts and, consequently, to implant.

Adult↗
PubMed2002

Embryonic lethality caused by apoptosis during gastrulation in mice lacking the gene of the ADP-ribosylation factor-related protein 1.

ADP-ribosylation factor (ARF)-related protein 1 (ARFRP1) is a membrane-associated GTPase with significant similarity to the family of ARFs. We have recently shown that ARFRP1 interacts with the Sec7 domain of the ARF-specific guanine nucleotide exchange factor Sec7-1/cytohesin and inhibits the ARF/Sec7-dependent activation of phospholipase D in a GTP-dependent manner. In order to further analyze the function of ARFRP1, we cloned the mouse Arfrp1 gene and generated Arfrp1 null-mutant mice by gene targeting in embryonic stem cells. Heterozygous Arfrp1 mutants developed normally, whereas homozygosity for the mutant allele led to embryonic lethality. Cultured homozygous Arfrp1 null-mutant blastocysts were indistinguishable from wild-type blastocysts. In vivo, they implanted and formed egg cylinder stage embryos that appeared normal until day 5. Between embryonic days 6 and 7, however, apoptotic cell death of epiblast cells occurred in the embryonic ectoderm during gastrulation, as was shown by histological analysis combined with terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling. Epiblast cells that would normally differentiate to mesodermal cells detached from the ectodermal cell layer and were dispersed into the proamniotic cavity. In contrast, the development of extraembryonic structures appeared unaffected. Our results demonstrate that ARFRP1 is necessary for early embryonic development during gastrulation.

ADP-Ribosylation Factors↗
PubMed2001

LIM-domain protein cysteine- and glycine-rich protein 2 (CRP2) is a novel marker of hepatic stellate cells and binding partner of the protein inhibitor of activated STAT1.

Activation of hepatic stellate cells is considered to be the main step in the development of liver fibrosis, which is characterized by the transition of quiescent vitamin-A-rich cells to proliferative, fibrogenic and contractile myofibroblasts. The identification of regulatory genes during early cell activation and transdifferentiation is essential to extend our knowledge of hepatic fibrogenesis. In liver, the gene CSRP2 is exclusively expressed by stellate cells, whereas no transcripts are detectable in hepatocytes, sinusoidal endothelial cells or Kupffer cells. The early activation of stellate cells induced by platelet-derived growth factor is accompanied by an enhanced expression of CSRP2. During later stages of transdifferentiation, the expression of CSRP2 in these cells is suppressed in vitro and in vivo. The CSRP2-encoded cysteine- and glycine-rich double-LIM-domain protein (CRP)2 is proposed to function as a molecular adapter, arranging two or more as yet unidentified protein constituents into a macromolecular complex. To identify these proteins and assign a cellular function to CRP2, a human cDNA library was screened with full-length CRP2 as bait in a yeast two-hybrid screen. The protein inhibitor of activated STAT1 ('PIAS1') was shown to associate selectively with the C-terminal LIM domain of CRP2. Physical interaction of both proteins in the cellular environment was confirmed by co-localization experiments with confocal laser scanning microscopy and co-immunoprecipitation analysis. These results establish CRP2 as a potential new factor in the JAK/STAT-signalling pathway and suggest that the suppression of CSRP2 might be a prerequisite for the myofibroblastic transition of hepatic stellate cells.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Cytokines regulate the capacity of CD8alpha(+) and CD8alpha(-) dendritic cells to prime Th1/Th2 cells in vivo.

Prior studies have shown that subclasses of dendritic cells (DC) direct the development of distinct Th populations in rodents and in humans. In the mouse, we have recently shown that administration of Ag-pulsed CD8alpha(-) DC induces a Th2-type response, whereas injection of CD8alpha(+) DC leads to Th1 differentiation. To define the DC-derived factors involved in the polarization of Th responses, we injected either subset purified from mice genetically deficient for IFN-gamma, IL-4, IL-12, or IL-10 into wild-type animals. In this work, we report that DC-derived IL-12 and IFN-gamma are required for Th1 priming by CD8alpha(+) DC, whereas IL-10 is required for optimal development of Th2 cells by CD8alpha(-) DC. The level of IL-12 produced by the DC appears to determine the Th1/Th2 balance in vivo. We further show that the function of DC subsets displays some flexibility. Treatment of DC with IL-10 in vitro induces a selective decrease in the viability of CD8alpha(+) DC. Conversely, incubation with IFN-gamma down-regulates the Th2-promoting capacities of CD8alpha(-) DC and increases the Th1-skewing properties of both subsets.

Animals↗
PubMed2001

Induction of AP-2alpha expression by adenoviral infection involves inactivation of the AP-2rep transcriptional corepressor CtBP1.

AP-2 transcription factors execute important functions during embryonic development and malignant transformation. Recently, we have isolated a transcriptional repressor of AP-2alpha expression, the novel Krüppel-related zinc finger protein AP-2rep (Klf12). Here, we show that repression of AP-2alpha transcription by AP-2rep is dependent on an N-terminal PVDLS motif that interacts specifically with the corepressor CtBP1 both in vivo and in vitro. This interaction motif was previously identified in the C-terminal region of the adenoviral oncoprotein E1A. Infection of both HeLa and PA-1 cells with adenovirus type 5 strongly induced AP-2alpha mRNA. Consistently, E1A was necessary and sufficient to mediate up-regulation of AP-2alpha. Transiently transfected wild-type E1A protein activated an AP-2rep sensitive cis-regulatory element of the AP-2alpha promoter, but E1A protein harboring a mutation in the PVDLS motif failed to activate. In summary, we conclude that the adenoviral oncoprotein E1A activates transcription from the endogenous AP-2alpha gene, an effect that involves transcriptional derepression of the AP-2alpha promoter by interaction of E1A with the AP-2rep corepressor CtBP1.

Adenoviridae↗
PubMed2001

Dendritic cell subsets and the regulation of Th1/Th2 responses.

Cells of the dendritic family are suited to perform two distinct functions at two discrete locations. In the peripheral tissues, dendritic cells (DC) act as sentinels for "dangerous" antigens. They then migrate into the lymphoid organ, where they initiate activation of T lymphocytes which are specific for these antigens. During their migration, DC shift from an antigen-capturing mode to a T cell sensitizing mode. In addition to switching on the immune response, subtypes of DC appear to influence the character of T cell differentiation, i.e. the Th1/Th2 balance. We will review the cellular and molecular bases of Th1-Th2 development by DC subsets, and will focus primarily, although not exclusively, on mouse DC.

Animals↗
PubMed2001

4-hydroxynonenal induces apoptosis, NF-kappaB-activation and formation of 8-isoprostane in vascular smooth muscle cells.

Oxidation of lipids is considered a key feature of atherogenesis. Lipid peroxidation products such as oxidized LDL or the bioactive aldehyde 4-hydroxynonenal (HNE) exert mitogenic effects on vascular smooth muscle cells (VSMC). These effects appear to be concentration-dependent since in addition to our previous reports on growth promotion at lower concentrations we here indicate induction of apoptosis in VSMC by 4-hydroxynonenal (HNE) at higher concentrations (100 micromol/L). In a line with HNE's previously documented effects on key mitogenic signaling elements, we also report on activation by this aldehyde of the redox-sensitive transcription factor NF-kappaB, a key regulator of apoptosis: HNE (1.0 micromol/L) induced DNA-binding of NF-kappaB in VSMC. The effect was inhibited by antioxidants, N-acetylcysteine and pyrrolidine dithio-carbamate. HNE caused phosphorylation but not degradation of the inhibitory subunit IkappaB-alpha. HNE itself acts as an oxidant as was investigated with measurements of 8-isoprostane which ranks among the most valuable available biomarkers of lipid peroxidation: HNE (1.0 micromol/L) increased 8-isoprostane levels in VSMC by 4.5-fold (p < 0.05). Compared to the controls, plasma samples from apoEnull mice exhibited elevated levels of 8-isoprostane (40 pg/mL, 3.2-fold increase) and the combined aldehydes HNE and malonaldehyde (1.5 micromol/L, 2.5-fold increase), (p < 0.05, resp). In addition, immunohistochemistry indicated the presence of HNE-protein adducts in atheroscerlotic lesions of apoEnull mice. Thus HNE is present in atherosclerotic tissue at concentrations that are bioactive in vitro. The data further indicate the involvement of the lipid peroxidation product HNE in atherogenesis.

Aldehydes↗
PubMed2001

Embryo fragmentation in vitro and its impact on treatment and pregnancy outcome.

OBJECTIVE: To determine the impact of embryo fragmentation on pregnancy, obstetric, and perinatal outcome. DESIGN: Retrospective analysis of embryo transfers that were homogeneous in regard to the degree of fragmentation. SETTING: Fertility center. PATIENT(S): A cohort of 460 fresh embryo transfers. INTERVENTION(S): A total of 164 pregnancies were analyzed for the incidence of antepartum complications during gestation, obstetric (multiple pregnancy, preterm delivery, cesarean section), and perinatal outcome (sex, birth weight, admission to neonatal intensive care unit, malformations). MAIN OUTCOME MEASURE(S): Implantation and clinical pregnancy rate, obstetric and perinatal outcome. RESULT(S): Embryo fragmentation and number of embryos per transfer showed a significant influence on clinical pregnancy and implantation rate. No such relation was found concerning complications, multiple pregnancy rate, incidence of cesarean section, gestation week, birth weight, and average time at the neonatology. On the other hand, pregnancies derived from bad-quality embryos had a significantly higher rate of malformations. CONCLUSION(S): The higher percentage of malformations found in bad-quality embryos may be due to a higher percentage of apoptotic features and chromosomal disorders. For ethical reasons, the transfer of embryos with >50% fragmentation should be considered only after consultation with the patient.

Adult↗
PubMed2001

[Dendritic cells and the control of the immune response].

Cells of the dendritic family are suited to perform two distinct functions at two discrete locations. In the peripheral tissues, DC act as sentinels for "dangerous" antigens. They then migrate into the lymphoid organ, where they initiate activation of T lymphocytes which are specific for these antigens. During their migration, DC shift from an antigen-capturing-mode to a T cell sensitizing mode. In addition to switching on the immune response, subtypes of DC appear to influence the character of T cell differentiation, i.e. the Th1/Th2 balance.

Animals↗
PubMed2001

Ecarin clotting time but not aPTT correlates with PEG-hirudin plasma activity.

BACKGROUND: Novel antithrombotic agents such as hirudin have shown promise in the therapy of acute coronary syndromes. PEG-hirudin (polyethyleneglycol conjugated hirudin) has been developed to provide a longer plasma half-life and more stable antithrombotic plasma levels. Privious trials indicated a narrow therapeutic window for hirudin and a number of aPTT (activated partial thromboplastin time)-monitored trials investigating hirudin in acute coronary syndromes had to be stopped because of intracranial bleeding complications. OBJECTIVES: The present study evaluates the ecarin clotting time (ECT), a parameter based on the conversion of prothrombin by the snake venom enzyme ecarin, for the monitoring of PEG-hirudin therapy. METHODS: Plasma from either healthy volunteers (n=20) or from patients (n=10) suffering from unstable angina pectoris (UAP) was spiked with increasing PEG-hirudin concentrations. In a prospective randomized clinical trial patients with UAP were treated with intravenous PEG-hirudin or heparin over 72 hours. Patients were randomized to the following treatment groups: (1) heparin control group, n=15; (2) PEG-hirudin low dose (0.1 mg/kg bolus, 0.01 mg/kg/h infusion), n=19; (3) intermediate dose (0.15 mg/kg and 0.015 mg/kg/h), n=17; 4) high-dose (0.2 mg/kg and 0.02 mg/kg/h), n=16. Spiked plasma samples and plasma from UAP patients treated with i.v. PEG-hirudin were analyzed for aPTT, ECT, and PEG-hirudin levels. RESULTS: A linear correlation up to the highest therapeutic concentrations could be observed between PEG-hirudin plasma concentrations and the ECT. This was true for both plasma samples spiked with PEG-hirudin in vitro as well as for samples taken from patients treated with i.v. PEG-hirudin (correlation coefficient 0.9, respect.) In contrast the aPTT did not show a reliable linear correlation to PEG-hirudin concentrations. CONCLUSION: Monitoring of PEG-hirudin therapy by ECT may help to avoid inadequate anticoagulation or overdosing. Thus, the safety and efficacy profile of PEG-hirudin therapy is likely to be enhanced by ECT monitoring.

Angina, Unstable↗