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Biomedical subjects

G Schubiger

Publications and source records attributed to G Schubiger.

At least 55 records · Page 3Linked to original sources

Independent roles of centrosomes and DNA in organizing the Drosophila cytoskeleton.

The early embryonic divisions of Drosophila melanogaster are characterized by rapid, synchronized changes of the nuclei and surrounding cytoskeleton. We report evidence that these changes are carried out by two separately organized systems. DNA was sufficient to cause assembly of nuclear lamina and the formation of nuclear membrane with pore structures. Free centrosomes were correlated with the formation of microtubule, microfilament and spectrin networks in the absence of nuclei. In addition, we found that the morphology of the cytoskeleton associated with the free centrosomes cycled in response to the embryonic cell cycle cues. These observations suggest that the centrosomes may be responsible for the organization of this extensive cytoskeleton. The early divisions may therefore result from the independent cycling of two systems, the nucleus and the surrounding cytoskeleton, that respond separately to the mitotic cues in the embryo and function together to give the synchronized early divisions. The Drosophila embryo has an "intermediate" mitotic system in which the nuclear membrane does not break down completely during mitosis. We speculate that the principles of cytoskeleton organization in this system may be different from those of the Xenopus "open" mitotic system.

Actin Cytoskeleton↗

[Nutrition in the first days of life: how many infants need supplemental food?].

A prospective study of 280 consecutive newborns (birth weight greater than 2500 g) showed that on discharge from hospital 88.5% were fully and 8.6% partly breastfed. Only 8 children (2.9%) were weaned. In the group of the fully breastfed infants, 8.5% received no prelacteal food or fluid, 85.9% received a 10% dextromaltose (DM) solution and in only 5.6% of the children was there additional feeding with an adapted milk formula for some days. This restrictive attitude concerning supplemental feeding involved no observable drawbacks. The increasing incidence of atopic diseases--especially cow's milk allergy, the evolution of which is essentially promoted by the administration of foreign proteins in the first days of life--justifies a feeding policy on these lines. The elimination of bovine proteins in the newborn period is of considerable preventive significance. On the other hand, restriction of water supply (10% DM solution) is not advisable in our opinion.

Bottle Feeding↗

Transient cholestatic hepatitis in a neonate associated with carbamazepine exposure during pregnancy and breast-feeding.

We report a 3-week-old boy with cholestatic hepatitis, most likely due to carbamazepine exposure during pregnancy and breastfeeding. Cholestasis resolved after cessation of nursing. Liver function test results and histological findings were compatible with a drug-induced hepatitis. Other causes were excluded. While carbamazepine-induced hepatitis is well known in children and adults, it has never been described in association with prenatal exposure and/or breast-feeding.

Breast Feeding↗

A genetic switch, based on negative regulation, sharpens stripes in Drosophila embryos.

The pair-rule genes hairy, runt, even-skipped, and fushi tarazu express their mRNAs and proteins in striped patterns in the Drosophila embryo at the blastoderm stage. Previous studies have shown that the generation of these patterns depends upon products of the gap genes and upon interactions between the pair-rule genes themselves. Here we show that blocking protein synthesis induces expression of each of the pair-rule mRNAs in virtually all regions of the embryo. Our observations together with genetic studies carried out in other laboratories suggest that negative feedback between the pair-rule genes plays a key role in striped expression of pair-rule genes. We propose that stable proteins, present in all regions of the embryo, first activate transcription of these pair-rule genes constitutively. Then, various combinations of unstable proteins repress their transcription in a patterned fashion; each stripe of accumulated products of a given pair-rule gene marks a region where it was not repressed. We develop this idea in mathematical form and demonstrate that a network of mutual repression by pair-rule genes can make each blastoderm nucleus into a genetic switch with two stable states. If preexisting gap gene patterns provide initial bias to the blastoderm nuclei, then the "bistable switch behavior" of the nuclei can refine an initially weak spatial bias into a final pattern of sharp stripes.

Animals↗

Extracellular protease production by Drosophila imaginal discs.

We are investigating the role of extracellular proteases in imaginal disc eversion to understand the mechanism that controls cell rearrangements within epithelia. We have identified three cation-dependent neutral proteases released by Drosophila leg discs everting in culture. Serine protease inhibitors block disc eversion and inhibit activity of disc proteases. The pattern of extracellular proteases changes when eversion is blocked with added protease inhibitors. Changes in protease activity occur when released disc proteases are treated with trypsin. Trypsin treatment of intact imaginal discs releases protease and inhibitor activities to the medium, indicating their presence on the cell surface before release. Our results suggest that extracellular proteases are required for imaginal disc morphogenesis and are regulated by more than one mechanism.

Animals↗

Experimental phenocopy of a minute maternal-effect mutation alters blastoderm determination in embryos of Drosophila melanogaster.

Maternal haploinsufficiency for a third chromosome Minute, M(3)i55, lowers rates of protein synthesis by approximately 30% during the syncytial nuclear cycles of early embryogenesis. The maternal effect of Mi55 also produces segmentation defects (denticle belt fusions) in the posterior abdomen of larvae. Furthermore, embryos from Minute mothers show abnormal expression patterns of the segmentation gene fushi tarazu (ftz) at the cellular blastoderm stage of embryogenesis. We developed a computer-aided analysis to describe the deviations in ftz expression which demonstrates that abnormally narrow ftz stripes occur in segment primordia that become fused in the larva. Unexpectedly, an abnormally wide ftz stripe occurs in segment primordia which do not develop abnormally. In addition, Mi55 produces a general narrowing of all ftz- interstripes. We phenocopied the Minute mutation by injecting wild-type embryos with cycloheximide concentrations which decreased protein synthesis rates to levels comparable with those of Minute embryos. Thus, a general decrease in protein synthesis during early embryogenesis leads to abnormal determination of posterior abdominal segment primordia.

Abdomen↗

[Neonatal vitamin K prophylaxis and vitamin k deficiency hemorrhages in Switzerland 1986-1988].

On the basis of an inquiry held in Switzerland in May 1988, over 99% of all newborn receive vitamin K prophylaxis, 59% orally and 41% intramuscularly. In the previous 2 1/2 years, ten cases of bleeding due to vitamin K deficiency had been observed, of which two were inadequately documented. In two children there was early haemorrhage and late haemorrhage in eight. The latter were all exclusively breast-fed and had received oral vitamin K prophylaxis. Seven presented with vitamin K deficiency due to cholestasis or chronic diarrhea. The only "idiopathic" case is insufficiently documented. The advantages and disadvantages of oral and intramuscular prophylaxis are discussed. A definite stand in favour of the one route or the other is not possible at present. However, the continuation of general prophylaxis is undoubtedly necessary.

Female↗

Spatial regulation of engrailed expression in the Drosophila embryo.

Novel patterns of engrailed RNA were observed in early Drosophila embryos injected with cycloheximide, an inhibitor of protein synthesis. From these patterns, we infer that there are several superimposed systems of spatial regulation which in combination localize engrailed expression in the embryo. Activation of engrailed transcription progresses with an anterior-to-posterior polarity. Superimposed are systems of negative regulation that repress expression in the anterior 30% of the embryo and in the interbands between stripes. We suggest that products of known segmentation genes are the repressors that suppress engrailed expression in interbands.

Animals↗

Cytoarchitecture and the patterning of fushi tarazu expression in the Drosophila blastoderm.

In the Drosophila embryo at the blastoderm stage, the segmentation gene fushi tarazu (ftz) is expressed in a seven-banded pattern. The generation of this pattern, like many other segmentation gene expression patterns, coincides with the formation of cell membranes around the blastoderm nuclei. To test the role of cellularization in resolving the banded ftz pattern, we used cytoskeletal inhibitors (colcemid and cytochalasin B) to block cellularization. We found that banded ftz RNA and protein patterns can form without cellular structure. We also tested the importance of rapid degradation of the ftz RNA, using cycloheximide to block degradation. RNA degradation is essential to maintain the banded ftz pattern in a syncytium, but is not required to maintain the pattern in a cellularized embryo. A latticework of cytoskeletal microtubules that forms during cellularization appears to be a key component in localizing the ftz mRNA. We conclude that RNA degradation and cellular structure normally work together to localize ftz RNA to its sites of synthesis.

Animals↗

Segmentally repeated pattern of expression of a cell surface glycoprotein in Drosophila embryos.

We report here that a previously described cell surface antigen (Brower, Smith & Wilcox, 1980) is expressed in a segmentally repeating pattern of stripes in the epidermis and nervous system of segmented Drosophila embryos. We also report that the antigenic activity is found on two closely related cell surface glycoproteins. The pattern of expression of this antigen is reminiscent of the expression of some segmentation genes and is affected by mutation of at least two of these genes, fushi tarazu and paired. Thus these glycoproteins are candidates for cell surface molecules involved in carrying out the patterning processes controlled by segmentation genes.

Animals↗

Repression and turnover pattern fushi tarazu RNA in the early Drosophila embryo.

Embryonic expression of transcripts from the Drosophila gene fushi tarazu (ftz) progresses through a series of spatial patterns, culminating in a seven-banded pattern at the cellular blastoderm stage. We studied the generation of this pattern using inhibitors of RNA synthesis (alpha-amanitin) and protein synthesis (cycloheximide). Injections of alpha-amanitin revealed that ftz RNA turns over extremely rapidly in the embryo, and we think that this may be essential to effect rapid changes in ftz RNA patterns. Injections of cycloheximide added to the normal domains of ftz expression, creating novel expression patterns that were dependent on the time of injection. These novel patterns suggest that two superimposed systems of repression establish the normal, seven-banded pattern of ftz expression. One system sets up a banded pattern over the entire length of the embryo, and the other restricts actual expression to the middle portion of the embryo.

Amanitins↗

[Meningococcal epidemic in a boarding school: a rifampicin-resistant secondary case while under chemoprophylaxis].

An epidemic of meningococcal disease after an influenza outbreak in a community of 49 boys (14-18 years) and 8 adults in a boarding-school is reported. The first patient died with all symptoms of the Waterhouse-Friderichsen syndrome. Several hours later, two other boys developed severe septicemia with meningitis and meningitis respectively. N. meningitidis group B susceptible to penicillin and rifampin was isolated. Within the next 8 hours, chemoprophylaxis with rifampin (600 mg twice daily) was started and maintained for 4 days for the whole community. Throat cultures had not been obtained before prophylaxis. Ten other symptomatic boys were admitted to the hospital and treated by penicillin infusion. The results of blood and cerebrospinal fluid cultures were negative, and treatment was therefore discontinued. Five days after the death of the first boy, another boy died with full-blown Waterhouse-Friderichsen syndrome while on chemoprophylaxis. The neisseriae isolated from this patient were rifampin-resistant. Serological investigations in all patients admitted to hospital revealed the existence of concomitant epidemic infection with influenza A and B in this school. We assume that the viral infection made way for the outbreak of the meningococcal disease and for the high rate of secondary meningococcal infection. Chemoprophylaxis with rifampin should not be continued for longer than 2 to 3 days, otherwise the risk of occurrence of rifampin resistant strains of N. meningitidis increases. Hitherto such strains have rarely been isolated in clinically manifest disease.

Adolescent↗

Parameters controlling transcriptional activation during early Drosophila development.

We studied transcription during the first 14 mitotic cycles of Drosophila development, by gel electrophoresis of RNA pulse-labeled in vivo. Synthesis of rRNA, tRNAs, 5S RNAs, snRNAs, poly(A)+ RNAs, and histone mRNAs is first detectable during cycle 11 or 12. Histone genes are transcribed during S phases, and reach maximal activation in cycle 12, whereas nonhistone genes are transcribed only in G2 periods, and reach maximal activation during late cycle 14. The high transcriptional activity characteristic of cycle 14 can be precociously induced by extending interphase with cycloheximide as early as, but not before, cycle 10. We conclude that all classes of genes become competent for activation during cycle 10, and that subsequent activation is differentially suppressed by functions associated with nuclear division.

Animals↗

Cell cycle control by the nucleo-cytoplasmic ratio in early Drosophila development.

We have studied the role of the nucleo-cytoplasmic ratio in the early development of Drosophila, using mutants and experimental manipulations that alter nuclear density. Haploid embryos produced by either maternal or paternal effect mutations compensate for haploidy by an extra nuclear division during the syncytial blastoderm stage. Decreasing the nucleo-cytoplasmic ratio in wild-type embryos by ligation can cause a similar extra blastoderm division. Conversely, increasing this ratio can cause the omission of a blastoderm division. The duration of mitotic cycles is affected by the nucleo-cytoplasmic ratio four cycles before the terminal blastoderm division. Transcription patterns in haploid embryos indicate that transcriptional activation is not directly controlled by the nucleo-cytoplasmic ratio, but may be an effect of the lengthening of interphase periods.

Animals↗

[Transcutaneous determination of bilirubin in the neonatal department: an analysis of its uses].

2000 newborns were evaluated before and 2000 after the introduction of transcutaneous bilirubinometry, with regard to frequency and methods of bilirubin determination. The number of blood sampling procedures was reduced by 79%. Transcutaneous bilirubinometry proves to be a safe method if correlation curves between the transcutaneous indices and the serum bilirubin of the individual nursery population are used together with set rules as to the indications for the controls by blood sampling (Recommendations of the Swiss Neonatology Group). A charge of sFr. 5.- to 7.- for each transcutaneous bilirubin evaluation is justified with regard to the reduced laboratory investigations.

Bilirubin↗