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Biomedical subjects

M Moser

Publications and source records attributed to M Moser.

At least 19 recordsLinked to original sources
PubMed2007

Radiation exposure to the population of Europe following the Chernobyl accident.

On the occasion of the 20th anniversary of the Chernobyl accident an attempt has been made to evaluate the impact of the Chernobyl accident on the global burden of human cancer in Europe. This required the estimation of radiation doses in each of the 40 European countries. Dose estimation was based on the analysis and compilation of data either published in the scientific literature or provided by local experts. Considerable variability has been observed in exposure levels among the European populations. The average individual doses to the thyroid from the intake of (131)I for children aged 1 y were found to vary from approximately 0.01 mGy in Portugal up to 750 mGy in Gomel Oblast (Belarus). Thyroid doses to adults were consistently lower than the doses received by young children. The average individual effective doses from external exposure and ingestion of long-lived radiocaesium accrued in the period 1986-2005 varied from approximately 0 in Portugal to approximately 10 mSv in Gomel Oblast (Belarus) and Bryansk Oblast (Russia). The uncertainties in the dose estimates were subjectively estimated on the basis of the availability and reliability of the radiation data that were used for dose reconstruction in each country.

Adult↗
PubMed2006

Incomplete denudation of oocytes prior to ICSI enhances embryo quality and blastocyst development.

BACKGROUND: Granulosa cells are essential mediators of oocyte maturation and fertilization. Because of the denudation of oocytes in preparation for ICSI, any potential positive effect of surplus cumulus cells (CCs) on further development would be unable to exert further effect. In order to evaluate the actual influence of adhering cumulus cells on further preimplantation development, this prospective study was carried out. METHODS: Sibling cumulus-oocyte complexes for 57 ICSI patients were split into a study group (incomplete denudation, n = 314) and a control group (complete denudation, n = 336). According to the cumulus cell pattern after partial denudation, mature gametes from the study group were further subdivided into type A oocytes, which showed several prominent CC clusters (n = 202), and type B (n = 75), which showed a more homogeneous pattern with CC covering the whole surface of the gamete. RESULTS: In immature oocytes, presence of adhered CCs led to a significant increase in resumption of meiosis (P < 0.01). Fertilization rate (P < 0.05) and ability to cleave (P < 0.01) was impaired in the study group, because of difficulties in ICSI of type B oocytes. By contrast, embryo morphology on days 2 (P < 0.01) and 3 (P < 0.05), as well as blastocyst formation, was better (P < 0.05) in the study group (55 blastocysts out of 88 zygotes) as compared to that in the control group (49/105). CONCLUSION: These data indicate that co-culture of oocytes with attached CCs may enhance preimplantation development.

Blastocyst↗
PubMed2006

Basal level of anti-Müllerian hormone is associated with oocyte quality in stimulated cycles.

BACKGROUND: Serum anti-Müllerian hormone (AMH) levels provide a powerful means for predicting ovarian response, which is reflected not only by the size of the primordial follicle pool but also by the quality of the oocytes. Considering a mutual interdependence between AMH-expressing somatic cells and gametes, this prospective morphological study was set up to evaluate whether extreme AMH levels represent diminished oocyte quality and developmental incompetence. METHODS: A total of 141 consecutive ICSI patients were subdivided into three groups using the 25th and 75th percentiles of the serum AMH levels (cycle day 3). In these three groups, morphology of all oocytes and fertilization rate, embryo quality and blastocyst formation were evaluated, and FSH, LH and estradiol (E(2)) levels were also measured. RESULTS: Cycle cancellation rate was correlated with AMH levels (P < 0.05). AMH groups 1 (<1.66 ng/ml) and 3 (>4.52 ng/ml) showed oocytes of lower quality [dark central granulation, aggregation of smooth endoplasmic reticulum (sER)] compared with the median group 2 (1.66-4.52 ng/ml). Basal serum FSH did not allow for adequate prognosis in terms of gamete appearance. Fertilization and further cleavage up to blastocyst stage was not affected by AMH levels. CONCLUSIONS: AMH seems to be superior to FSH in predicting both oocyte number and quality.

Adult↗
PubMed2006

Evidence for a differential functional regulation of the two beta(3)-integrins alpha(V)beta(3) and alpha(IIb)beta(3).

The functional regulation of integrins is a major determinant of cell adhesion, migration and tissue maintenance. The binding of cytoskeletal proteins to various sites of integrin cytoplasmic domains is a key mechanism of this functional regulation. Expression of recombinant integrin alpha(IIb)beta(3) and alpha(M)beta(2) lacking the GFFKR-region in CHO cells results in constitutively activated integrins. In contrast, CHO cells stably expressing either a GFFKR-deleted alpha(V(del))beta(3) or a FF to AA-substituted alpha(V(AA))beta(3) do not reveal a constitutively activated integrin. Adhesion to immobilized fibrinogen is strongly impaired in alpha(V(del))beta(3) or alpha(V(AA))beta(3)-expressing cells, whereas it is not impaired in alpha(IIb)beta(3) and alpha(M)beta(2), both lacking the GFFKR-region. In a parallel plate flow chamber assay, alpha(V)beta(3)-expressing cells adhere firmly to fibrinogen and spread even at shear rates of 15 to 20 dyn/cm(2), whereas alpha(V(del))beta(3) or alpha(V(AA))beta(3) cells are detached at 15 dyn/cm(2). Actin stress fiber formation and focal adhesion plaques containing alpha(V)beta(3) are observed in alpha(V)beta(3) cells but not in alpha(V(del))beta(3) or alpha(V(AA))beta(3)-expressing cells. As an additional manifestation of impaired outside-in signaling, phosphorylation of pp125(FAK) was reduced in these cells. In summary, we report that the GFFKR-region of the alpha(V)-cytoplasmic domain and in particular two phenylalanines are essential for integrin alpha(V)beta(3) function, especially for outside-in signaling. Our results suggest that the two beta(3)-integrins alpha(IIb)beta(3) and alpha(V)beta(3) are differentially regulated via their GFFKR-region.

Animals↗
PubMed2006

Prolonged asystole provoked by head-up tilt testing.

We describe a patient with a history of neurocardiogenic syncopes who had a positive headup tilt test that resulted in an lasting asystole lasting 34 seconds. However, the previously carried out Schellong test with a 30-min phase of standing showed a normal result. The patient showed typical orthostatic symptoms while tilted at the angle of 75 degrees. Shortly before asystole occurred, heart rate variability showed high frequency bands, indicating vagal stimulation. The pathophysiology of neurocardiogenic syncope (NCS) in context with heart rate variability is discussed. This patient was successfully treated with propranolol. This case shows the utility of a provocative head-up tilt test in establishing the diagnosis of NCS. If the Schellong test is normal, still further examination by tilt-table test is indispensable.

Adult↗
PubMed2005

Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries.

OBJECTIVES: To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures. DESIGN: Multinational retrospective cohort study of cancer mortality. SETTING: Cohorts of workers in the nuclear industry in 15 countries. PARTICIPANTS: 407 391 workers individually monitored for external radiation with a total follow-up of 5.2 million person years. MAIN OUTCOME MEASUREMENTS: Estimates of excess relative risks per sievert (Sv) of radiation dose for mortality from cancers other than leukaemia and from leukaemia excluding chronic lymphocytic leukaemia, the main causes of death considered by radiation protection authorities. RESULTS: The excess relative risk for cancers other than leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of causes of death related or unrelated to smoking indicate that, although confounding by smoking may be present, it is unlikely to explain all of this increased risk. The excess relative risk for leukaemia excluding chronic lymphocytic leukaemia was 1.93 per Sv (< 0 to 8.47). On the basis of these estimates, 1-2% of deaths from cancer among workers in this cohort may be attributable to radiation. CONCLUSIONS: These estimates, from the largest study of nuclear workers ever conducted, are higher than, but statistically compatible with, the risk estimates used for current radiation protection standards. The results suggest that there is a small excess risk of cancer, even at the low doses and dose rates typically received by nuclear workers in this study.

Dose-Response Relationship, Drug↗
PubMed2005

Possible applications of a non-contact 1.48 microm wavelength diode laser in assisted reproduction technologies.

Recently, one laser system has been introduced in IVF fulfilling all safety requirements, while achieving a high standard of reproducibility in terms of ablation diameter. This 1.48 microm wavelength indium-gallium-arsenic-phosphorus (InGaAsP) semiconductor laser offers a variety of laser applications to the embryologist. On the one hand, zona pellucida of oocytes or embryos can be manipulated in order to facilitate ICSI or biopsy and assist hatching, and on the other, spermatozoa may be paralysed or immobilized prior to usage. To conclude, the 1.48 microm diode laser provides a promising tool for the microdissection of subcellular targets. The diode laser stands out due to the rapidity, the simplicity and the safety of the procedure which is supported by healthy offspring after laser application.

Animals↗
PubMed2005

Enhanced blood coagulation and fibrinolysis in mice lacking histidine-rich glycoprotein (HRG).

Histidine-rich glycoprotein (HRG) is a serum protein belonging to the cystatin superfamily. HRG may play a regulatory role in hemostasis and innate immunity. However, this role is uncertain because of a lack of rigorous testing in an animal model. We generated mice lacking the translation start point of exon 1 of the Hrg gene, effectively resulting in a null mutation (Hrg-/-). The mice were viable and fertile but had no HRG in their blood. Antithrombin activity in the plasma of Hrg-/- mice was higher than in the plasma of heterozygous Hrg+/- or wild-type Hrg+/+ mice. The prothrombin time was shorter in Hrg-/- mice than in Hrg+/- and Hrg+/+ mice. Bleeding time after tail tip amputation in Hrg-/- mice was shorter than in Hrg+/+ mice. The spontaneous fibrinolytic activity in clotted blood of Hrg-/- mice was higher than in Hrg+/+ mice. These findings suggest that HRG plays a role as both an anticoagulant and an antifibrinolytic modifier, and may regulate platelet function in vivo.

Animals↗
PubMed2004

Complete oocyte activation failure after ICSI can be overcome by a modified injection technique.

BACKGROUND: Complete fertilization failure after ICSI is a rare event, and it may happen repeatedly even in cases of normal sperm parameters and good ovarian response. In these cycles, alternative ICSI techniques may prove useful. METHODS: Our modified ICSI (mICSI) is characterized by aspiration close to the opposite membrane (the region of the mitochondria with a high inner mitochondrial membrane potential) which is followed by central deposition of the sperm. The method was applied prospectively to ICSI cycles of patients with a history of complete fertilization failure in previous ICSI cycles. In parallel, mICSI was compared with conventional ICSI in terms of further preimplantation development and treatment outcome. RESULTS: In patients with previous ICSI failures using conventional ICSI (no 2Pn zygotes out of 70 oocytes that had been injected) application of mICSI led to adequate fertilization (53.6%) and pregnancy rates (33.3%) (P < 0.001; P < 0.01). In patients without previous failed fertilization, no improvement in the rates of fertilization, blastocyst formation, implantation or clinical pregnancy could be seen. CONCLUSIONS: Our data indicate that the present version of ICSI is a reliable alternative to conventional ICSI. However, although it overcomes oocyte-dependent activation failure, routine application does not improve the overall results.

Adult↗
PubMed2004

Laser-assisted zona pellucida thinning prior to routine ICSI.

BACKGROUND: In MII oocytes showing difficult oolemma breakage, ICSI can cause an increase in the degeneration rate. This may be overcome by laser-assisted ICSI using a 5-10 micro m opening in the zona pellucida for injection. However, such a small opening might impair the hatching process, especially if assisted hatching is applied in addition. In order to prevent this, the present study used routine injection through an area of zona pellucida in which laser zona thinning had been applied, providing for both a reduced mechanical stress to the oocyte and assisted hatching. METHODS: This prospective study involved 100 cycles with 1016 MII oocytes. Conventional ICSI (control group) was compared with a modified laser-assisted ICSI (study group) in sibling oocytes. In the latter group oocytes were injected through an extended area of zona thinning. RESULTS: Degeneration rate was significantly lower in the study group (P < 0.004). There were no differences in fertilization, or formation and quality of blastocysts. In the study group embryo quality on day 2 was significantly better (P = 0.004) and herniation of day 5 blastocysts was increased (P = 0.005). Rates of implantation and pregnancy were not affected. However, on day 3 laser-assisted ICSI proved beneficial (P = 0.038) in terms of clinical pregnancy rate. CONCLUSIONS: The new method combines a less invasive ICSI technique with assisted hatching. Our preliminary data indicate that in addition to an improved oocyte survival, this new approach increases the hatching rate in vitro, which may explain the increase in pregnancy rate, at least in day 3 transfers.

Adult↗
PubMed2004

Characterization and expression pattern of the novel MIA homolog TANGO.

A novel human gene, TANGO, encoding a MIA ('melanoma inhibitory activity') homologous protein was identified by a gene bank search. TANGO, together with the homologous genes MIA, OTOR (FPD, MIAL) and MIA2 define a novel gene family sharing important structural features, significant homology at both the nucleotide and protein level, and similar genomic organization. The four members share 34-45% amino acid identity and 47-59% cDNA sequence identity. TANGO encodes a mature protein of 103 amino acids in addition to a hydrophobic secretory signal sequence. Sequence homology confirms the highly conserved SH3 structure present also in MIA, OTOR and MIA2. Thus, it appears that there are a number of extracellular proteins with SH3-fold like structures. Interestingly, in situ hybridization, RT-PCR and Northern Blots revealed very broad TANGO expression patterns in contrast to the highly restricted expression patterns previously determined for the other members of the MIA gene family. The only cells lacking TANGO expression are cells belonging to the hematopoetic system. High levels of TANGO expression were observed both during embryogenesis and in adult tissues.

Amino Acid Sequence↗
PubMed2004

The fate of dendritic cells in a mouse model of liver ischemia/reperfusion injury.

Ischemia/reperfusion during liver transplantation triggers a complex cascade of inflammatory events that may lead to organ dysfunction. Herein, we investigated the consequences of hepatic ischemia/reperfusion on liver dendritic cells. Liver damage was documented by increased levels of serum alanine aminotransferase and by histopathology showing large areas of hepatocyte cytolysis. MHC class II+ CD45-B220 F4/80 dendritic cells were detected in necrotic areas 20 hours after reperfusion. Dendritic cells freshly isolated from reperfused livers displayed a mature phenotype characterized by upregulated expression of B7 costimulatory molecules; MHC-class II, and CD1d molecules. As shown by real-time PCR, IL-10, and TGF-beta mRNA accumulated in liver dendritic cells isolated after reperfusion, whereas IL-12p40 mRNA levels were decreased and IFN-gamma mRNA levels were unchanged. These results suggest that hepatic ischemia/reperfusion results in maturation of dendritic cells, which preferentially produce inhibitory cytokines.

Alanine Transaminase↗
PubMed2004

Peyronie's disease fibroblasts demonstrate tumorigenicity in the severe combined immunodeficient (SCID) mouse model.

Peyronie's disease is a localized connective tissue disorder, caused by trauma to the erect penis, which results in cellular proliferation and excess extracellular matrix production within the tunica albuginea of the penis. We have previously demonstrated that cells derived from Peyronie's disease plaque tissue demonstrate increased cell growth, increased S-phase on flow cytometry, stabilization and inactivation of p53, and consistent morphologic transformation, all suggesting that these cells are biologically transformed. Severe combined immunodeficient (SCID) mice have been used extensively to study the pathobiology of malignant and benign tissue and cells. This study was undertaken to determine if Peyronie's derived fibroblasts had the potential to demonstrate tumorigenicity in the SCID mouse model, thus confirming their biologically transformed nature. Cultured fibroblasts were derived from three sources, namely, plaque tissue excised from men with Peyronie's disease, tunical tissue excised from young men with congenital penile curvature and neonatal foreskins. BALB/C SCID mice were divided into three groups and each group was inoculated with cultured fibroblasts from each of the three different sources. All animals were evaluated regularly and maintained in isolation for a period of 3 months following inoculation. All SCID mice inoculated with cells derived from Peyronie's disease plaque tissue (n=10) developed subcutaneous nodules at a mean time period of 2.5+/-0.5 months following injection. The mean maximum dimension and weight of the nodules at the time of killing the animal was 1.1+/-0.2 cms and 0.6+/-0.2 g, respectively. Histologically, the nodules were composed of large pleomorphic epithelioid cells with a high mitotic activity, which were negative for cytokeratin but positive for vimentin. None of the SCID mice inoculated with cells cultured from either normal tunica (n=5) or foreskin (n=5) developed subcutaneous nodules. In conclusion, the tumorigenic nature of Peyronie's disease plaque-derived fibroblasts sheds further light on the pathobiologic characteristics of these cells. Specifically, these data confirm that cells cultured from Peyronie's disease plaque are biologically transformed. Future refinement and study of this animal model may permit a more complete understanding of the pathophysiology of Peyronie's disease and fibromatoses in general. Furthermore, such an animal model may, in the future, allow a more ready evaluation of the therapeutic interventions for Peyronie's disease.

Animals↗
PubMed2004

New options for prenatal diagnosis in autosomal recessive polycystic kidney disease by mutation analysis of the PKHD1 gene.

Due to the poor prognosis of severe autosomal recessive polycystic kidney disease (ARPKD), there is a strong demand for prenatal diagnosis (PD). Reliable PD testing is possible by molecular genetic analysis only. Although haplotype-based analysis is feasible in most cases, it is associated with a risk of misdiagnosis in families without pathoanatomically proven diagnosis. Linkage analysis is impossible in families where DNA of the index patient is not available. Direct mutation analysis of the recently identified polycystic kidney and hepatic disease 1 gene opens new options in families to whom a reliable PD cannot be offered on the basis of linkage analysis. We for the first time report two cases with PD based on mutation detection, illustrating the new options for PD in ARPKD.

Consanguinity↗
PubMed2004

Differential capacity of CD8+ alpha or CD8- alpha dendritic cell subsets to prime for eosinophilic airway inflammation in the T-helper type 2-prone milieu of the lung.

BACKGROUND: Different subsets of dendritic cells (DCs), identified in mouse spleen by their differential expression of CD8 alpha, can induce different T-helper (Th) responses after systemic administration. CD8 alpha(-) DCs have been shown to preferentially induce Th type 2 (Th2) responses whereas CD8 alpha(+) DCs induce Th1 responses. OBJECTIVE: To study if these DC subsets can still induce different Th responses in the Th2-prone milieu of the lung and differentially prime for eosinophilic airway inflammation, typical of asthma. METHODS: Donor mice first received daily Flt3L injections to expand DC numbers. Purified CD8 alpha(+) or CD8 alpha(-) splenic DCs were pulsed with ovalbumin (OVA) or phosphate-buffered saline and injected intratracheally into recipient mice in which carboxyfluorescein diacetate succinimidyl ester-labelled OVA-specific T cell receptor transgenic T cells had been injected intravenously 2 days earlier. T cell proliferation and cytokine production of Ag-specific T cells were evaluated in the mediastinal lymph nodes (MLNs) 4 days later. The capacity of both subsets of DCs, to prime for eosinophilic airway inflammation was determined by challenging the mice with OVA aerosol 10 days later. RESULTS: CD8 alpha(-) DCs migrated to the MLN and induced a vigorous proliferative T cell response accompanied by high-level production of IL-4, IL-5, IL-10 and also IFN-gamma during the primary response and during challenge with aerosol, leading to eosinophilic airway inflammation. In the absence of migration to the MLN, CD8 alpha(+) DCs still induced a proliferative response with identical levels of IFN-gamma but reduced Th2 cytokines compared with CD8 alpha(-) DCs, which led to weak eosinophilic airway inflammation upon OVA aerosol challenge. Unpulsed DCs did not induce proliferation or cytokine production in Ag-specific T cells. CONCLUSION: CD8 alpha(-) DCs are superior compared with CD8 alpha(+) DCs in inducing Th2 responses and eosinophilic airway inflammation in the Th2-prone environment of the lung.

Animals↗
PubMed2004

Typical metabolic traits of two Oenococcus oeni strains isolated from Valpolicella wines.

AIMS: Physiological comparison of two indigenous Oenococcus oeni strains, U1 and F3 isolated in the same area (Valpolicella, Italy) in order to select a performant starter for MLF in wine. METHODS AND RESULTS: Growth rate, sugar and malate metabolism in FT80 media at pH 5.3 and 3.5 were analysed. The amount of total protein synthesized and the level of expression of the small Hsp Lo18 were evaluated by radiolabelling and immunodetection experiments after heat (42 degrees C), acid (pH 3.5) and ethanol (12% v/v) stresses. Strain U1 showed significantly lower specific growth rate and growth yield in acid conditions than strain F3. However, strain U1 had a higher malate consumption capacity at pH 3.5 than strain F3, in relation with an higher malolactic activity determined on whole cells. Strain U1 exhibited about half the total protein synthesis level than strain F3, but both strains expressed Lo18 similarly. Evaluation of malolactic fermentation (MLF) performance by microvinification trials was carried out. Strain U1 was able to complete MLF, whereas strain F3 degraded malic acid partially when inoculated in Amarone wine. CONCLUSIONS: Considering its performances in microvinifications experiments, strain U1 could be a good candidate for malolactic starter as an alternative to deficient commercial starters.

Ethanol↗
PubMed2003

Status of oral healthcare in long-term care facilities.

Oral health is a fundamental component in the overall well-being and quality of life for elders living in long-term care facilities. Effective oral care interventions must not only involve recognising the importance of oral health in this population, but giving oral hygiene the same priority as other care practices in long-term care settings.

Aged↗