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G Schubiger

Publications and source records attributed to G Schubiger.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1993

Dynamic changes in microtubule configuration correlate with nuclear migration in the preblastoderm Drosophila embryo.

Drosophila embryogenesis is initiated by a series of syncytial mitotic divisions. The first nine of these divisions are internal, and are accompanied by two temporally distinct nuclear movements that lead to the formation of a syncytial blastoderm with a uniform monolayer of cortical nuclei. The first of these movements, which we term axial expansion, occurs during division cycles 4-6 and distributes nuclei in a hollow ellipsoid underlying the cortex. This is followed by cortical migration, during cycles 7-10, which places the nuclei in a uniform monolayer at the cortex. Here we report that these two movements differ in their geometry, velocity, cell-cycle dependence, and protein synthesis requirement. We therefore conclude that axial expansion and cortical migration are mechanistically distinct, amplifying a similar conclusion based on pharmacological data (Zalokar and Erk, 1976). We have examined microtubule organization during cortical migration and find that a network of interdigitating microtubules connects the migrating nuclei. These anti-parallel microtubule arrays are observed between migrating nuclei and yolk nuclei located deeper in the embryo. These arrays are present during nuclear movement but break down when the nuclei are not moving. We propose that cortical migration is driven by microtubule-dependent forces that repel adjacent nuclei, leading to an expansion of the nuclear ellipsoid established by axial expansion.

Animals↗
PubMed1993

Vitamin K1 concentration in breast-fed neonates after oral or intramuscular administration of a single dose of a new mixed-micellar preparation of phylloquinone.

The plasma disposition of a new mixed-micellar preparation (KONAKION MM, Roche) of phylloquinone (vitamin K1) has been studied in 25 healthy, fully breast-fed, newborn babies, randomized to receive a single dose of either 1.5 mg i.m. (11 babies) or 3 mg p.o. (14 babies). Venous blood samples were collected at 25 h, 4 days, and 24 days. After p.o. administration, the median plasma phylloquinone concentration increased to 89 ng/ml after 24 h, then decreased to 51 ng/ml after 4 days; the respective concentrations after i.m. injection were 146 ng/ml and 34 ng/ml. The higher plasma phylloquinone level in the i.m. group after 24 h was not statistically significant compared with that of the p.o. group, but the reversed higher concentration in the p.o. group after 4 days was significant (p < 0.01). After 24 days the median plasma phylloquinone had decreased to 0.44 ng/ml (range 0.19-1.44) and 1.05 ng/ml (range 0.37-1.87) in the p.o. and i.m. groups, respectively. There was a significant difference between these plasma concentrations (p < 0.01). They were within or above the reference adult fasting range (0.17-0.68 ng/ml). The narrow range of plasma concentrations at 24 h and 4 days suggests a greater consistency of absorption from this micellar preparation than from other emulsion-based preparations. Further studies are required to assess the long-term protection of a single oral dose against late hemorrhagic disease of the newborn. Until such time, breast-fed babies given this preparation orally should receive (an) additional dose(s).

Administration, Oral↗
PubMed1992

Temporal regulation in the early embryo: is MBT too good to be true?

The question of how early embryonic events are temporally regulated has traditionally been tied to the mid-blastula transition (MBT). This concept has directed the studies in Xenopus and influenced the studies in other organisms. By examining the weaknesses in the concept of MBT, we hope to refocus the study of temporal regulation on the many developmental transitions that do exist and to clear the way for an alternative viewpoint that emphasizes the similarities between developmental processes in different organisms.

Animals↗
PubMed1991

N-acetylglutamate synthetase deficiency: diagnosis, management and follow-up of a rare disorder of ammonia detoxication.

We report the 9-year follow-up of a patient suffering from N-acetylglutamate synthetase deficiency, an urea cycle disorder leading to severe neonatal hyperammonaemia. Hitherto two patients from two families with this inborn error of metabolism had been observed. Our management consisted mainly of a protein-restricted diet and oral treatment with N-carbamylglutamate, an activator of carbamylphosphate synthetase, together with arginine or citrulline. The somatic development was normal whereas a moderate psychomotor retardation was diagnosed. The patient died after an episode of coma and prolonged generalized convulsions at the age of 9.5 years.

Acetyltransferases↗
PubMed1991

Magnetic resonance imaging in infantile encephalopathy with cerebral calcification and leukodystrophy.

Three children, one pair of siblings and a sporadic case, with "infantile (familial) encephalopathy with cerebral calcification and leukodystrophy" are reported. Neuroimaging studies demonstrated extensive bilateral calcifications particularly in paraventricular location and within the cerebral white matter. MRI, performed in two infants, confirmed marked white matter involvement with diffuse delay of myelination. This condition can be added to the growing list of leukodystrophies.

Brain↗
PubMed1991

Temporal regulation of gene expression in the blastoderm Drosophila embryo.

The Drosophila embryo undergoes a developmental transition during cycle 14 when it initiates asynchronous mitotic cycles and markedly increases its rate of zygotic transcription. The nucleo-cytoplasmic ratio has been proposed to be the single factor that temporally regulates this developmental transition. We altered the ratio in the embryo and analyzed the consequences on the cell cycle program and on the transcripts of specific genes. These genes were chosen because their transcripts normally undergo changes in pattern during cycle 14. We found evidence that the nucleo-cytoplasmic ratio is read and interpreted locally to regulate the cell cycle program. Based on the response of the transcripts to changes in the ratio, we found evidence that at least two classes of temporal regulatory mechanisms control these transcripts. We therefore propose two corresponding classes of transcripts: (1) nucleo-cytoplasmic ratio dependent; and (2) nucleo-cytoplasmic ratio independent or time correlated. The temporal regulation of the ratio-independent transcripts may be dependent on developmental time. We conclude that multiple modes of temporal regulation underlie the events of the developmental transition in Drosophila embryogenesis.

Animals↗