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Biomedical subjects

K Fiedler

Publications and source records attributed to K Fiedler.

At least 55 records · Page 3Linked to original sources

[Logistic regression analysis of the influence of residential environment, residential hygiene and life style on the incidence and duration of acute respiratory disease in small children].

659 children aged between 1 and 2 years were examined in respect of the influence of the children's-facility, residential environment, residential hygiene, and way of life, as well as in respect of the influence of selected sociological factors on the number and duration of acute respiratory diseases (ARD). The evaluation of the results by using logistical regressions analysis came--among other things--to following factors, that correlated with a risen morbidity, respectively an extended duration of the illness (> 3 diseases in 6 months; > 20 days in 6 months). Apartments with wet walls, dark and too noisy apartments, children's-rooms with two outside walls, single window pane, outside-wall-gas-heaters, room-air-humidity too low, space for children in day-nurseries < 4 sqm, no carrying out of hardening-steps for the children, wind-influence to the open space of the children's-facility too strong, and shift-working by the mother.

Acute Disease↗

VIP17/MAL, a proteolipid in apical transport vesicles.

VIP17 is a proteolipid enriched in the CHAPS-insoluble complexes from MDCK cells, and a candidate component of the molecular machinery responsible for the sorting and targeting of proteins to the apical surface. Cloning and sequencing of the cDNA encoding the protein revealed that it is the canine homolog of the human and rat MAL proteins. Analysis by immunofluorescence microscopy of epitope-tagged VIP17/MAL expressed transiently in BHK cells and stably in MDCK cells revealed a perinuclear, vesicular, and plasmalemmal staining. In MDCK cells the distribution was mainly in vesicular structures in the apical cytoplasm. These and other results suggest that VIP17/MAL is an important component in vesicular trafficking cycling between the Golgi complex and the apical plasma membrane.

Amino Acid Sequence↗

Cloning and characterization of MVP17: a developmentally regulated myelin protein in oligodendrocytes.

The remarkable quantities of myelin membrane produced by oligodendrocytes has led us to examine the mechanisms involved in the sorting and transport of proteins and lipids during myelinogenesis. Noting that it has been proposed that proteins destined for the apical surface of polarized epithelial cells co-cluster with glycolipid-rich microdomains during sorting and transport from the trans-Golgi network (Simons and van Meer: Biochemistry 27:6197-6202, 1988; Simons and Wandinger-Ness: Cell 62:207-210, 1990), we hypothesized that the glycolipid-rich oligodendrocytes may adopt this mechanism for myelinogenesis. Protein-lipid complexes from oligodendrocytes and myelin were isolated utilizing detergent insolubility and two-dimensional gel electrophoresis. A developmentally regulated protein, MVP17 (myelin vesicular protein of 17 kDa), was identified. Microsequencing of the N-terminal peptide revealed a high homology to human T-cell MAL protein (Alonso and Weissman: Proc Natl Acad Sci USA 84:1997-2001, 1987). The corresponding MVP17 cDNA was isolated from an oligodendrocyte cDNA library. The predicted protein sequence showed 88.9% identity with MAL, and the hydrophobicity profile suggested four transmembrane domains. In vitro translation demonstrated a signal at the deduced Mr of approximately 17 kDa. Northern analyses indicated that MVP17 mRNA expression is restricted to brain and kidney and that this expression is up-regulated in oligodendrocytes and brain during the period of active myelination. These data suggest that MVP17 is involved in myelin biogenesis and/or myelin function.

Amino Acid Sequence↗

Prohibitin, an antiproliferative protein, is localized to mitochondria.

Prohibitin is a ubiquitously expressed protein with antiproliferative properties. When rat prohibitin tagged with a carboxy-terminal c-Myc epitope was expressed in baby hamster kidney cells the protein was targeted to mitochondria. In immunofluorescence microscopy prohibitin colocalized with a mitochondrial marker E3. Immunoelectron microscopy revealed that prohibitin was associated with the periphery of mitochondria. The amino-terminus of prohibitin shares characteristics of the known mitochondrial import signals, and positioning of the tag at the N-terminus causes accumulation of the protein in the cytoplasm. These findings help to direct functional studies on prohibitin and suggest that a mitochondrial protein may act as a tumor suppressor.

Amino Acid Sequence↗

Annexin XIIIb: a novel epithelial specific annexin is implicated in vesicular traffic to the apical plasma membrane.

The sorting of apical and basolateral proteins into vesicular carriers takes place in the trans-Golgi network (TGN) in MDCK cells. We have previously analyzed the protein composition of immunoisolated apical and basolateral transport vesicles and have now identified a component that is highly enriched in apical vesicles. Isolation of the encoding cDNA revealed that this protein, annexin XIIIb, is a new isoform of the epithelial specific annexin XIII sub-family which includes the previously described intestine-specific annexin (annexin XIIIa; Wice, B. M., and J. I. Gordon. 1992. J. Cell Biol. 116:405-422). Annexin XIIIb differs from annexin XIIIa in that it contains a unique insert of 41 amino acids in the NH2 terminus and is exclusively expressed in dog intestine and kidney. Immunofluorescence microscopy demonstrated that annexin XIIIb was localized to the apical plasma membrane and underlying punctate structures. Since annexins have been suggested to play a role in membrane-membrane interactions in exocytosis and endocytosis, we investigated whether annexin XIIIb is involved in delivery to the apical cell surface. To this aim we used permeabilized MDCK cells and a cytosol-dependent in vitro transport assay. Antibodies specific for annexin XIIIb significantly inhibited the transport of influenza virus hemagglutinin from the TGN to the apical plasma membrane while the transport of vesicular stomatitis virus glycoprotein to the basolateral cell surface was unaffected. We propose that annexin XIIIb plays a role in vesicular transport to the apical plasma membrane in MDCK cells.

Amino Acid Sequence↗

VIP36, a novel component of glycolipid rafts and exocytic carrier vesicles in epithelial cells.

In simple epithelial cells, apical and basolateral proteins and lipids in transit to the cell surface are sorted in the trans-Golgi network. We have recently isolated detergent-insoluble complexes from Madin-Darby canine kidney cells that are enriched in glycosphingolipids, apical cargo and a subset of the proteins of the exocytic carrier vesicles. The vesicular proteins are thought to be involved in protein sorting and include VIP21-caveolin. The vesicular protein VIP36 (36 kDa vesicular integral membrane protein) has been purified from a CHAPS-insoluble residue and a cDNA encoding VIP36 has been isolated. The N-terminal 31 kDa luminal/exoplasmic domain of the encoded protein shows homology to leguminous plant lectins. The transiently expressed protein is localized to the Golgi apparatus, endosomal and vesicular structures and the plasma membrane, as predicted for a protein involved in transport between the Golgi and the cell surface. It is diffusely localized on the plasma membrane but can be redistributed by antibody modulation into caveolae and clathrin-coated pits. We speculate that VIP36 binds to sugar residues of glycosphingolipids and/or glycosylphosphatidyl-inositol anchors and might provide a link between the extracellular/luminal face of glycolipid rafts and the cytoplasmic protein segregation machinery.

Amino Acid Sequence↗

Glycosphingolipid-enriched, detergent-insoluble complexes in protein sorting in epithelial cells.

In simple epithelial cells, the delivery of apical and basolateral proteins to the cell surface is mediated by sorting in the trans-Golgi network and transport via separate vesicular carriers. In order to identify the molecular machinery involved in protein sorting, we have recently studied a detergent-insoluble complex in Madin-Darby canine kidney (MDCK) cells, following CHAPS extraction of exocytic carrier vesicles, specifically including the apical marker protein influenza hemagglutinin (HA). Previously, a Triton X-100 insoluble membrane residue that was enriched in glycosylphosphatidylinositol-anchored (GPI) proteins and glycolipids was characterized and implicated in transport to the apical cell surface [Brown, D., & Rose, J. (1991) Cell 68, 533-544]. In this report, the protein compositions of the CHAPS and Triton complexes have been compared by two-dimensional gel analysis. Only a few major membrane proteins are found in the complexes. The protein compositions are qualitatively similar, but differ quantitatively in the individual components. The CHAPS complex is depleted of GPI-linked proteins and retains a minor fraction of lipids similar in composition to that of the Triton X-100 insoluble complex. We propose that in vivo the complexes form part of a sorting platform that mediates protein segregation and delivery to the apical cell surface.

Animals↗

Two pregnancies after in-vitro fertilization with spermatozoa from alloplastic spermatocoeles.

Two case reports describe successful in-vitro fertilization (IVF) of oocytes of two 28-year-old women with epididymal spermatozoa aspirated from alloplastic spermatocoeles of the husbands. Both men suffered from complete ejaculatory failure, which was caused by paraplegia in the first and by radical surgery of an embryonic carcinoma of the testis in the second. Motile spermatozoa were aspirated in the first case 4 months after implantation of the spermatocoele, and in the second at 1 month. For the first couple, IVF treatment led to a singleton pregnancy; the child has since been born. In the second couple, IVF treatment resulted in a twin pregnancy, with intra-uterine abortion of one gestational sac. The resulting singleton pregnancy is still ongoing.

Adult↗

Constructive processes in person cognition.

The notion of constructive memory processes is imported from research on eyewitness memory to the area of social cognition. Mere questioning about the applicability of personality attributes to a target person is shown to affect subsequent memory-based judgements of that person. These constructive influences are to be distinguished, conceptually, from the global notion of priming effects. In Expt 1, the target person was first described as an extravert; afterwards, subjects had to indicate whether either desirable aspects of extraversion (self-confidence) or undesirable aspects (exhibitionism) apply to the target or not. Mere questioning resulted in a congruent judgment bias towards the questioned attributes that did not generalize to a global halo effect. Experiment 2 replicated the basic finding and demonstrated that this phenomenon is independent of a generation effect (i.e. the memory advantage of self-generated inferences). These results are interpreted in terms of (a) a reframing of the categorical distribution representing the information about the target person in memory and (b) a regressive tendency to assume intermediate default values rather than extreme values for questioned attributes under uncertainty. Alternative explanations in terms of demand effects or a conformation bias cannot provide sufficient accounts. The relevance of constructive processes to understanding self-fulfilling prophecies and other phenomena in social interaction is discussed.

Adult↗

Prenatal diagnosis by amniocentesis in 82 pregnancies after in vitro fertilization.

We report on the outcome of 82 amniocenteses (AC) carried out during pregnancies after in vitro fertilization (IVF) from 1-1-1985 to 31-12-1989. The main indication for amniocentesis was a maternal age of greater than or equal to 35 years. In 48 cases, we found an anterior placenta and assumed that this was related to the position in which the uterine embryo transfer was performed. In six pregnancies, we found an abnormal karyotype, including two cases of trisomy 21; the two couples decided for abortion. Four aberrations in the fetal karyotypes were also present in either the mother or the father, the resulting children are healthy. The further course of pregnancies after IVF and AC was characterized by a higher incidence of toxemia, uterine bleeding before the 28th week of gestation, abruptio placentae, and premature deliveries, when compared to the course of pregnancies after spontaneous conception. We believe that these occurrences were not caused by AC, as the incidence was higher in all our pregnancies after IVF (without AC) and has also been reported in pregnancies after ovarian hyperstimulation without IVF. Therefore, we see no reason to renounce AC after IVF. However, the special risks inherent in pregnancies after IVF must always be discussed with the couple.

Adult↗

Mobilization of cognitive resources and the generation effect.

The generation effect refers to the memory advantage of words that have been generated rather than read. Such a read-generate comparison confounds qualitative task differences and raises methodological problems. A revised methodology is proposed circumventing these problems in that the encoding task is held constant and all stimuli have to be generated, but the degree of generativeness (i.e. the amount of cueing) is varied. In Experiment 1, 1, the (refined version of the) generation effect is demonstrated in a within-subjects design; with increasing generation activity left to the subject, free recall performance increases. No effect is obtained for degree of target masking. The same finding is replicated and shown to be independent of self-paced study time when generative activity is manipulated between subjects (Experiment 2) or within subjects (Experiment 3). As all learning trials involve generation, encoding time is controlled statistically, and free recall is used as a measure of memory, this refined generation effect cannot be explained as an artifact of selective attention or elaboration. Rather, generative activity seems to increase the mobilization of cognitive resources. This motivational account is supported by Experiment 4 showing an enhanced generation effect for positive mood.

Adult↗

Charged residues are major determinants of the transmembrane orientation of a signal-anchor sequence.

Uncleaved signal-anchor sequences of membrane proteins inserted into the endoplasmic reticulum initiate the translocation of either the amino-terminal or the carboxyl-terminal polypeptide segment across the bilayer. Which topology is acquired is not determined by the apolar segment of the signal but rather by the hydrophilic sequences flanking it. To study the role of charged residues in determining the membrane topology, the insertion of mutants of the asialoglycoprotein receptor H1, a single-spanning protein with a cytoplasmic amino terminus, was analyzed in transfected COS-7 cells. When the charged amino acids flanking the hydrophobic signal were mutated to residues of opposite charge, half the polypeptides inserted with the inverted orientation. When, in addition, the amino-terminal domain of the mutant protein was truncated, approximately 90% of the polypeptides acquired the inverted topology. The transmembrane orientation appears to be primarily determined by the charges flanking the signal sequence but is modulated by the domains to be translocated.

Amino Acid Sequence↗