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G Schubiger

Publications and source records attributed to G Schubiger.

At least 19 recordsLinked to original sources
PubMed1998

A molecular basis for transdetermination in Drosophila imaginal discs: interactions between wingless and decapentaplegic signaling.

We are investigating how Drosophila imaginal disc cells establish and maintain their appendage-specific determined states. We have previously shown that ectopic expression of wingless (wg) induces leg disc cells to activate expression of the wing marker Vestigial (Vg) and transdetermine to wing cells. Here we show that ectopic wg expression non-cell-autonomously induces Vg expression in leg discs and that activated Armadillo, a cytosolic transducer of the Wg signal, cell-autonomously induces Vg expression in leg discs, indicating that this Vg expression is directly activated by Wg signaling. We find that ubiquitous expression of wg in leg discs can induce only dorsal leg disc cells to express Vg and transdetermine to wing. Dorsal leg disc cells normally express high levels of decapentaplegic (dpp) and its downstream target, optomotor-blind (omb). We find that high levels of dpp expression, which are both necessary and sufficient for dorsal leg development, are required for wg-induced transdetermination. We show that dorsalization of ventral leg disc cells, through targeted expression of either dpp or omb, is sufficient to allow wg to induce Vg expression and wing fate. Thus, dpp and omb promote both dorsal leg cell fate as well as transdetermination-competent leg disc cells. Taken together, our results show that the Wg and Dpp signaling pathways cooperate to induce Vg expression and leg-towing transdetermination. We also show that a specific vg regulatory element, the vg boundary enhancer, is required for transdetermination. We propose that an interaction between Wg and Dpp signaling can explain why leg disc cells transdetermine to wing and that our results have implications for normal leg and wing development.

Animals↗
PubMed1997

Prevention of vitamin K deficiency bleeding: efficacy of different multiple oral dose schedules of vitamin K.

UNLABELLED: There is consensus that late vitamin K deficiency bleeding (VKDB) should be prevented by vitamin K prophylaxis. One single dose of 1 mg vitamin K1 is effective if given i.m. or s.c., but not if given orally. Repeated oral doses might be as effective as the parenteral dose but the optimal dose regimen remains to be established. Different oral dose schedules are presently used in different countries. In Australia, Germany, The Netherlands and Switzerland active surveillance data on late VKDB were collected in a similar manner and failure rates compared. Identical case definitions were used. There were three basic strategies for oral and one for parenteral vitamin K prophylaxis for healthy newborns in the four countries: (1) daily supplementation of low dose vitamin K (25 micrograms) for breast-fed infants (The Netherlands); (2) 3 x 1 mg orally [Australia (January 1993-March 1994) and Germany (December 1992-December 1994)]; (3) 1 mg vitamin K i.m. (Australia since March 1994); and (4) 2 x 2 mg vitamin K (new mixed micellar preparation) (Switzerland). The respective failure rates per 100,000 live births (including cases given all recommended doses and those given incomplete prophylaxis) were for strategy: (1) 0.2 (0-1.3) in The Netherlands; (2) 2.3 (95% CI 1.6-3.4) in Germany and 2.5 (1.1-4.8) in Australia (oral prophylaxis); (3) Australia (i.m. prophylaxis) 0 (0-0.9); and (4) 3.6 (0.7-10.6) in Switzerland. The failure rates for complete prophylaxis only were: strategy (1) 0 (0-0.7) in The Netherlands; (2) 1.8 (1.1-2.8) in Germany and 1.5 (0.5-3.6) in Australia; (3) Australia (i.m.) 0 (0-0.9); and (4) 1.2 (0-6.5) in Switzerland. CONCLUSIONS: The Australian data confirm that three oral doses of 1 mg vitamin K are less effective than i.m. vitamin K prophylaxis. A daily low oral dose of 25 micrograms vitamin K1 following an initial oral dose of 1 mg after birth for exclusively breast-fed infants may be as effective as parenteral vitamin K prophylaxis. The effectiveness of the "mixed-micellar" preparation of vitamin K1 needs further study.

Administration, Oral↗
PubMed1997

UNICEF/WHO baby-friendly hospital initiative: does the use of bottles and pacifiers in the neonatal nursery prevent successful breastfeeding? Neonatal Study Group.

UNLABELLED: To promote breastfeeding, UNICEF/WHO have launched the "baby-friendly hospital initiative" focusing on hospital care routines during delivery and the first days of life. In industrialised countries, two aspects of the initiative have raised controversy: how do restriction of supplemental feedings and ban of bottles and pacifiers affect long-term breastfeeding performance? From ten centres 602 healthy newborns were randomly assigned either to a UNICEF group with restrictive fluid supplements and avoidance of bottles and pacifiers during the first 5 days of life, or to a standard group with conventional feeding practice. Breastfeeding was encouraged in both groups. The main study endpoints were the prevalences of breast-feeding on day 5, and after 2, 4 and 6 months. Of the newborns 46% violated the UNICEF protocol, mostly because of maternal requests to give a pacifier or supplements by bottle. In the standard group, the drop-out rate was 9.7%. No significant differences in breastfeeding frequency and duration could be found: (UNICEF vs standard) day 5: 100% vs 99%; 2 months: 88% vs 88%; 4 months: 75% vs 71%; 6 months: 57% vs 55%. Inclusion of drop-outs due to pacifier use did not alter the results. CONCLUSION: In our study population fluid supplements offered by bottle with or without the use of pacifiers during the first 5 days of life were not associated with a lower frequency or shorter duration of breastfeeding during the first 6 months of life.

Breast Feeding↗
PubMed1997

A vertical (pseudodominant) pattern of inheritance in the autosomal recessive disease primary hyperoxaluria type 1: lack of relationship between genotype, enzymic phenotype, and disease severity.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disease caused by a deficiency of alanine:glyoxylate aminotransferase (encoded by the AGXT gene). Primary hyperoxaluria type 1 is characterized by the elevated urinary excretion of oxalate and glycolate, and the deposition of insoluble calcium oxalate in the renal parenchyma and urinary tract. In the present study, we investigated an unusual family containing four affected individuals in two different generations. Based on our genetic, enzymic, metabolic, and clinical analyses, we have come to the following conclusions. First, although the pattern of inheritance of PH1 is usually horizontal (ie, all patients in the same generation), as expected for an autosomal recessive disease, it can sometimes show a vertical (pseudodominant) pattern of inheritance (ie, patients in more than one generation) due to the segregation within a family of three, rather than two, mutant AGXT alleles. Second, affected members of such a family can manifest very different clinical phenotypes both within and between generations. Although the clinical differences between generations might be at least partly due to differences in AGXT genotype, differences can equally occur within the same generation in individuals who possess the same AGXT genotype. Finally, individuals with PH1 at the level of the AGXT genotype might remain asymptomatic and undiagnosed for many years. The consequences of these findings for the clinical management and genetic counseling of families with PH1 are profound and wide-ranging.

Adolescent↗
PubMed1997

Plasma vitamin K1 and PIVKA-II after oral administration of mixed-micellar or cremophor EL-solubilized preparations of vitamin K1 to normal breast-fed newborns.

BACKGROUND: Vitamin K1 prophylaxis in neonates is required for prevention of vitamin K1 deficiency bleeding. Although intramuscular administration of vitamin K1 is safe, this invasive method is not generally accepted. We therefore examined the pharmacokinetics of two orally administered vitamin K1 preparations in normal, fully breast-fed newborns. METHODS: Within 1 hour of birth, each baby was randomized to a 2 mg dose of either a conventional Cremophor EL-solubilized preparation of vitamin K1 (Konakion drops, F. Hoffmann-La Roche, n = 16), or a new mixed-micellar preparation of vitamin K1 (Konakion MM, F. Hoffmann-La Roche, n = 14). The concentrations of vitamin K1, des-gamma-carboxyprothrombin (PIVKA-II), and total bound bilirubin were measured in plasma samples taken at 24 hours, 4 days, and 24 days after birth. RESULTS: The median concentration of plasma vitamin K1 was higher at all three time points in the group that received the mixed-micellar preparation, but the difference was only significant (p < 0.05) at 4 days. At 24 hours and 4 days, PIVKA-II was detectable in a significantly lower proportions of infants receiving the new mixed-micellar preparation than those receiving the Cremophor EL preparation (21% vs. 75% at 24 hours, p < 0.05 and 14% vs. 50% at 4 days, p < 0.05). None of the infants in the study had detectable PIVKA-II levels 24 days after birth. CONCLUSIONS: Our results suggest that when given orally, the mixed-micellar preparation is superior to the conventional formulation because it increases plasma vitamin K1 concentrations to higher levels, suggesting superior bioavailability, and decreases PIVKA-II concentrations more efficiently, suggesting a faster pharmacodynamic response.

Biological Availability↗
PubMed1996

Activation of transcription in Drosophila embryos is a gradual process mediated by the nucleocytoplasmic ratio.

We have observed that zygotic transcription does not initiate at a single point in Drosophila embryos. Rather, a gene initiates transcription in a few nuclei of a fraction of embryos. During succeeding cycles, the frequency of transcribing embryos, and of nuclei transcribing in those embryos, gradually increases. For the fushi tarazu (ftz) gene, the timing of this process is regulated by the concentration of the maternally loaded, repressing transcription factor tramtrack (ttk). Altering the dose of Ttk protein in embryos shifts the activation of ftz transcription either forward or backward during development but does not effect Krüppel (Kr) activation. We have observed that the transcription of several genes, including ftz, is triggered in embryos at a critical nuclear density; therefore, we suggest that titration of transcription factors like ttk by the nucleocytoplasmic ratio triggers zygotic transcription in Drosophila.

Animals↗
PubMed1996

Ectopic expression of wingless in imaginal discs interferes with decapentaplegic expression and alters cell determination.

We have expressed the segment polarity gene wingless (wg) ectopically in imaginal discs to examine its regulation of both ventral patterning and transdetermination. By experimentally manipulating the amount of Wg protein, we show that different thresholds of Wg activity elicit different outcomes, which are mediated by regulation of decapentaplegic (dpp) expression and result in alterations in the expression of homeotic genes. A high level of Wg activity leads to loss of all dorsal pattern elements and the formation of a complete complement of ventral pattern elements on the dorsal side of legs, and is correlated with repression of dpp expression. wg expression in dorsal cells of each disc also leads to dose-dependent transdetermination in those cells in homologous discs such as the labial, antennal and leg, but not in cells of dorsally located discs. When dpp expression is repressed by high levels of Wg, transdetermination does not occur, confirming that dpp participates with wg to induce transdetermination. These and other experiments suggest that dorsal expression of wg alters disc patterning and disc cell determination by modulating the expression of dpp. The dose-dependent effects of wg on dpp expression, ventralization of dorsal cells and transdetermination support a model in which wg functions as a morphogen in imaginal discs.

Animals↗
PubMed1996

Autonomous and nonautonomous Notch functions for embryonic muscle and epidermis development in Drosophila.

The Notch (N) gene encodes a cell signaling protein that mediates neuronal and epidermal determination in Drosophila embryos. N also regulates several aspects of myogenic development; embryos lacking N function have too many muscle founder cells and fail to properly differentiate somatic muscle. To identify cell-autonomous requirements for Notch function during muscle development, we expressed a Notch minigene in the mesoderm, but not in the ectoderm, of amorphic N-embryos. In these embryos, muscle founder hypertrophy is rescued, indicating that Notch is autonomously required by mesoderm cells to regulate the proper number of muscle founders. However, somatic muscle differentiation is only partially normalized, suggesting that Notch is also required in the ectoderm for proper muscle development. Additionally, mesodermal expression of Notch partially rescues epidermal development in overlying neurogenic ectoderm. This is unexpected, since previous studies suggest that Notch is autonomously required by proneural ectoderm cells for epidermal development. Mesodermal expression of a truncated Notch protein lacking the extracellular domain does not rescue ventral epidermis, suggesting that the extra-cellular domain of Notch can non-autonomously rescue epidermal development across germ layers.

Animals↗
PubMed1995

[Computer-supported patient history: a workplace analysis].

Since 1991, an extensive computer network has been developed and implemented at the Cantonal Hospital of Lucerne. The medical applications include computer aided management of patient charts, medical correspondence, and compilation of diagnosis statistics according to the ICD-9 code. In 1992, the system was introduced as a pilot project in the departments of pediatrics and pediatric surgery of the Lucerne Children's Hospital. This new system has been prospectively evaluated using a workplace analysis. The time taken to complete patient charts and surgical reports was recorded for 14 days before and after the introduction of the computerized system. This analysis was performed for both physicians and secretarial staff. The time delay between the discharge of the patient and the mailing of the discharge letter to the family doctor was also recorded. By conventional means, the average time for the physician to generate a patient chart (26 minutes, n = 119) was slightly lower than the time needed with the computer system (28 minutes, n = 177). However, for a discharge letter, the time needed by the physician was reduced by one third with the computer system and by more than one half for the secretarial staff (32 and 66 minutes conventionally; 22 and 24 minutes respectively with the computer system; p < 0.0001). The time required for the generation of surgical reports was reduced from 17 to 13 minutes per patient and the processing time by secretaries from 37 to 14 minutes. The time delay between the discharge of the patient and the mailing of the discharge letter was reduced by 50% from 7.6 to 3.9 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation Studies as Topic↗
PubMed1995

Genetic characterization of ms (3) K81, a paternal effect gene of Drosophila melanogaster.

The vast majority of known male sterile mutants of Drosophila melanogaster fail to produce mature sperm or mate properly. The ms(3) K81(1) mutation is one of a rare class of male sterile mutations in which sterility is caused by developmental arrest after sperm entry into the egg. Previous studies showed that males homozygous for the K81(1) mutation produce progeny that arrest at either of two developmental stages. Most embryos arrest during early nuclear cycles, whereas the remainder are haploid embryos that arrest at a later stage. This description of the mutant phenotype was based on the analysis of a single allele isolated from a natural population. It was therefore unclear whether this unique paternal effect phenotype reflected the normal function of the gene. The genetic analysis and initial molecular characterization of five new K81 mutations are described here. Hemizygous conditions and heteroallelic combinations of the alleles were associated with male sterility caused by defects in embryogenesis. No other mutant phenotypes were observed. Thus, the K81 gene acted as a strict paternal effect gene. Moreover, the biphasic pattern of developmental arrest was common to all the alleles. These findings strongly suggested that the unusual embryonic phenotype caused by all five new alleles was due to loss of function of the K81+ gene. The K81 gene is therefore the first clear example of a strict paternal effect gene in Drosophila. Based on the embryonic lethal phenotypes, we suggest that the K81+ gene encodes a sperm-specific product that is essential for the male pronucleus to participate in the first few embryonic nuclear divisions.

Alleles↗
PubMed1995

Wingless induces transdetermination in developing Drosophila imaginal discs.

Drosophila imaginal discs, the precursors of the adult fly appendages, have been the subject of intensive developmental studies, particularly on cell determination. Cultured disc fragments are recognized not only for the ability to maintain their determined state through extra cell divisions but also for the ability to transdetermine, or switch to the determined state of a different disc. An understanding of transdetermination at a molecular level will provide further insight into the requirements for maintaining cell determination. We find that ectopic expression of the Drosophila gene wingless induces transdetermination of foreleg imaginal disc cells to wing cells. This transdetermination occurs in foreleg discs of developing larvae without disc fragmentation. The in situ-transdetermining cells localize to the dorsal region of the foreleg disc. This wingless-induced transdetermination event is remarkably similar to the leg-to-wing switch that occurs after leg disc culture. Thus we have identified a new approach to a molecular dissection of transdetermination.

Animals↗
PubMed1995

Ectoderm induces muscle-specific gene expression in Drosophila embryos.

We have inhibited normal cell-cell interactions between mesoderm and ectoderm in wild-type Drosophila embryos, and have assayed the consequences on muscle development. Although most cells in gastrulation-arrested embryos do not differentiate, they express latent germ layer-specific genes appropriate for their position. Mesoderm cells require proximity to ectoderm to express several muscle-specific genes. We show that ventral ectoderm induces mesoderm cells to express nautilus (a MyoD homologue) and to differentiate somatic myofibers, whereas dorsal ectoderm induces mesoderm cells to express visceral and cardiac muscle-specific genes. Our findings suggest that muscle determination in Drosophila is regulated by induction between germ layers during gastrulation.

Animals↗
PubMed1994

[Effect of conjugated PRP vaccines on the incidence of invasive diseases caused by Haemophilus influenzae Type B in childhood].

Prior to the introduction of conjugate vaccines, Haemophilus influenzae type b (Hib) was the leading cause of severe invasive infections in young children, in Switzerland as in other countries. From 1976 to 1990, 150 children were treated for Hib meningitis at the Children's Hospital of Lucerne, corresponding to an annual incidence of 9.2 cases per 100,000 children aged under 15 years. In the same time period, the case fatality rate for meningitis was 4%. 87.3% of the meningitis cases occurred among children aged under 5 years. For this age group an annual incidence of 26.4 cases per 100,000 children was calculated. From 1979 to 1990, 141 children were hospitalized for epiglottitis, corresponding to an annual incidence of 10.9 cases per 100,000 children aged under 15. The introduction of conjugated vaccines resulted in a significant reduction in the frequency of invasive Hib disease. From 1991 to 1992, 9 cases each of meningitis and epiglottitis were observed. In 1993, only one case of meningitis and 2 cases of epiglottitis were seen. For children under 15 years these 21 cases represent annual incidences of 3.2 cases of meningitis and 3.6 cases of epiglottitis per 100,000 children. 2 of 10 meningitis cases occurred in twice vaccinated children under 2 years of age with no signs of immunodeficiency, and another case was seen in a 5-month-old infant vaccinated with only one dose. Assuming a vaccination coverage of 70% among children under 5 during the years 1991 and 1992, the calculated efficacy is 80 to 85% for the vaccine PRP-D in this predominantly affected age group during the period when only this vaccine was available.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

How an actin network might cause fountain streaming and nuclear migration in the syncytial Drosophila embryo.

We show here using time-lapse video tapes that cytoplasmic streaming causes nuclear migration along the anterior-posterior axis (axial expansion) in the early syncytial embryo of Drosophila melanogaster. Using confocal microscopy and labeled phalloidin we explore the distribution of F-actin during axial expansion. We find that a network of F-actin fibers fills the cytoplasm in the embryo. This actin network partially disassembles around the nuclei during axial expansion. Our observations of normal development, fixed embryos, and drug injection experiments indicate that disassembly of the actin network generates cytoplasmic movements. We suggest that the cell cycle regulates disassembly of the actin network, and that this process may be mediated directly or indirectly by the microtubules. The cytoplasmic movements we observe during axial expansion are very similar to fountain streaming in the pseudopod of amoebae, and by analogy with the pseudopod we propose a working hypothesis for axial expansion based on solation-contraction coupling within the actin network.

Actin Cytoskeleton↗
PubMed1993

Egg ligation alters the Bcd protein gradient and segmentation gene expression in embryos of Drosophila.

A concentration gradient of the anterior morphogen Bicoid (Bcd) plays a key role in the specification of cell fates in the early Drosophila embryo. We found that introduction of a membrane barrier across the embryo results in increased levels of Bcd protein on the anterior side of the barrier and decreased levels on the posterior side, consistent with a blockage in the postulated anterior-to-posterior translocation of Bcd protein. The expression patterns of downstream segmentation genes were in large part consistent with their regulation by the Bcd morphogen. However, some aspects of the patterns did not correlate with the altered Bcd distribution, suggesting that other morphogens also regulate the anteroposterior pattern. Our results suggest that axial translocation of morphogens is critical for establishing a well-proportioned body plan.

Animals↗