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Biomedical subjects

M Hug

Publications and source records attributed to M Hug.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of tracheal tube cuff diameters with internal transverse diameters of the trachea in children.

BACKGROUND: In this study, we evaluated the ratio of the cuff diameters of the Microcuff paediatric tracheal tube (Microcuff PET, Weinheim, Germany) to fluoroscopically measured internal transverse tracheal diameters in children from birth to adolescence. METHODS: With Institutional Ethics Committee approval and parental consent, we measured the internal transverse tracheal diameters from fluoroscopy images in children undergoing cardiac catheterization requiring general anaesthesia with oro-tracheal intubation. Minimal tracheal sealing pressures were assessed at standardized respirator settings. Internal transverse tracheal diameters were compared with cuff diameters at 20 cmH2O cuff pressure. Linear regression analysis was employed to assess the correlation of tracheal diameters with age, height and weight, and to assess the correlation of the cuff/tracheal diameter ratio with sealing pressures. For all tests, P < 0.05 was considered to be statistically significant. RESULTS: One hundred and forty-five patients were studied (62 girls; 83 boys). Transverse tracheal diameters correlated well with age (r = 0.890; P < 0.0001), height (r = 0.900; P < 0.0001) and weight (r = 0.882; P < 0.0001). Tracheal sealing pressures ranged from 4 to 18 cmH2O. The ratio of the tracheal tube cuff diameter to the internal transverse tracheal diameter ranged from 1.06 in tubes with internal diameters of 6.0 and 4.5 mm to 2.01 in a tube with an internal diameter of 3.5 mm (median, 1.43), and did not correlate with tracheal sealing pressures (r = 0.021, P = 0.7999). CONCLUSIONS: The residual diameters of the Microcuff paediatric tracheal tube cuffs were sufficient to cover the measured internal transverse tracheal diameters of children from birth to adolescence. This allowed the internal tracheal mucosal surface to be draped and the trachea to be sealed at very low cuff pressures.

Adolescent↗
PubMed2003

[Percutaneous carotid angioplasty with stent implantation and protection device against embolism--a prospective study of 100 consecutive cases].

BACKGROUND AND OBJECTIVE: Percutaneous transluminal angioplasty and stenting of internal carotid artery stenosis has been increasingly practiced as an alternative to carotid embolectomy, particularly since the development of cerebral protection devices. 100 consecutive elective percutaneous carotid stenting procedures were carried out in our centre. We here present the clinical outcome and follow-up of these patients. PATIENTS AND METHODS: 69 men and 22 women, average age 69 +/- 10 years with symptomatic (41 %) or asymptomatic and progressive (59 %) > 80 % stenosis of the internal carotid artery were treated. There was a high rate of co-morbidity and a high vascular risk. 64 % would have been excluded from the NASCET trial because of one, 31 % because of two or more contraindications. In 84 % of the patients symptomatic coronary artery disease was present, in 13 % a significantly reduced left ventricular function (LVEF < 40 %).Pre- and post-procedure all patients were given aspirin and clopidogrel and examined by an independent neurologist. 99 stents were placed with the use of an embolic protection device (28 times with distal balloon occlusion, 72 times with a filter device).The follow-up period averaged 10.4 +/- 8.2.(1 - 29 months). RESULTS: The angiographic success rate was 99 %. During the procedure transient neurological symptoms were experienced by 4 % of patients (2x TIA,2x PRIND) and a minor stroke resulted in two. In 90 % of the interventions debris was collected from the embolic protection device. The maximum diameter of particles was 311+/-431 (30 - 1850) micro m. There was some correlation between patients' symptoms prior to stent implantation and maximum particle size (p < 0,04),but none with any other angiographic or clinical parameters. The combined endpoint (death and any stroke) after 30 days occurred 5 times (5 %). A subacute stent thrombosis occurred once, restenosis in two patients. CONCLUSION: Carotid artery stenting with use of a distal embolic protection device is a feasible new alternative to carotid endarterectomy. Our results indicate high success rate and low complication rates, even in patients with severe co-morbidity. The results compare well with surgical figures. Our favourable results are supported by data emerging from current randomized multicenter trials and a large therapy registry. However, long-term follow-up will still be required.

Adult↗
PubMed1998

[Progressive cardiomyopathic lentiginosis].

We report on a 30-year-old man with progressive cardiomyopathic lentiginosis. This syndrome is first described by Polani and Moynahan 1972. They distinguish between the earlier described multiple lentigines syndrome, the LEOPARD syndrome (L-entiginosis, E-lectrocardiographic conduction defects, O-cular hypertelorism, P-ulmonary stenosis, A-bnormalities of genitalia, R-etardation of growth, D-eafness) and the progressive cardiomyopathic syndrome. The progressive cardiomyopathic syndrome is characterised by multiple symmetrical lentigines, hypertrophic obstructive cardiomyopathy and retardation of growth. All characteristics were present in our patient with only mild right ventricular hypertrophic cardiomyopathy.

Adult↗
PubMed1997

Mechanisms of developmental regulation in Trypanosoma brucei: a polypyrimidine tract in the 3'-untranslated region of a surface protein mRNA affects RNA abundance and translation.

Salivarian trypanosomes are extracellular parasites of mammals that are transmitted by tsetse flies. The procyclic acidic repetitive proteins (PARPs) are the major surface glycoproteins of the form of Trypanosoma brucei that replicates in the fly. The abundance of PARP mRNA and protein is very strongly regulated, mostly at the post-transcriptional level. The 3'-untranslated regions of two PARP genes are of similar lengths, but are dissimilar in sequence apart from a 16mer stem-loop that stimulates translation and a 26mer polypyrimidine tract. Addition of either of these PARP 3'-untranslated regions immediately downstream of a reporter gene resulted in developmental regulation mimicking that of PARP. We show that the PARP 3'-UTR reduces RNA stability and translation in bloodstream forms and that the 26mer polypyrimidine tract is necessary for both effects.

Animals↗
PubMed1997

Intracellular pH in rat pancreatic ducts.

In order to study the mechanism of H+ and HCO3- transport in a HCO3- secreting epithelium, pancreatic ducts, we have measured the intracellular pH (pHi) in this tissue using the pH sensitive probe BCECF. We found that exposures of ducts to solutions containing acetate/acetic acid or NH4+/NH3 buffers (20 mmol/l) led to pHi changes in accordance with entry of lipid-soluble forms of the buffers, followed by back-regulation of pHi by duct cells. In another type of experiment, changes in extracellular pH of solutions containing HEPES or HCO3-/CO2 buffers led to significant changes in pHi that did not seem to be back-regulated efficiently by duct cells. The sensitivity of pHi to the inhibitor HOE 694 and to changes in Na+ gradients, indicate that the Na+/H+ exchanger is present in this epithelium. Similarly, the sensitivity to Cl- and HCO3- gradients indicated the presence of the Cl-/HCO3- exchanger. Under some conditions, these exchangers can be invoked to regulate cell pH.

Animals↗
PubMed1996

Evidence for a Na+-Ca2+ exchanger in rat pancreatic ducts.

Only recently has it been recognized that intracellular Ca2+ is an important cellular mediator in pancreatic ducts. The aim of the present study was to characterize the Ca2+ efflux pathway in ducts freshly prepared from rat pancreas. Lowering of extracellular Na+ concentration resulted in a significant increase in intracellular Ca2+. This effect was fast, reversible, dependent on the extracellular Na+ concentration and did not correlate with intracellular pH changes. It was abolished in Ca2+-free solutions, indicating that the outwardly directed Na+ gradient was directly coupled to a flufenamate insensitive Ca2+ influx. Removal and reintroduction of extracellular Na+ induced transient hyperpolarization and depolarization of Vm, respectively. Taken together, our data indicate that pancreatic ducts possess an electrogenic Na+-Ca2+ exchanger, which under control conditions is responsible for transporting Ca2+ out of resting duct cells.

Acetates↗
PubMed1996

Transcriptional repression by methylation: cooperativity between a CpG cluster in the promoter and remote CpG-rich regions.

Cytosine methylation of binding sites for transcription factors is a straightforward mechanism to prevent transcription, while data on an indirect mechanism, by methylation outside of the factor binding sites, are still scarce. We have studied the latter effect using a model promoter construct. For this, a 69 bp G + C rich DNA segment with a cluster of 14 CpG sites was inserted between upstream lexA sites and the TATA box. Transcription was measured in transient transfection assays with lexA-VP16 as an activating factor. When the entire plasmid was methylated at all CpGs before transfection, transcription was blocked (to 3% residual activity), whereas transcription was only mildly inhibited (to 60%) by methylation of a control plasmid that lacked the 69 bp CpG cluster. However, the effect could not simply be attributed to methylation of the CpG cluster: neither a methylated CpG cluster in an otherwise methylation-free reporter gene plasmid, nor the methylated plasmid with an unmethylated CpG cluster, inhibited transcription considerably (69% and 44% remaining activity, respectively). The data presented here suggest that a minimal length of methylated DNA in the promoter is required for repression, and imply that concomitant methylation of CpGs in the promoter region and in remote sequences can cooperatively block transcription, without the need to methylate any binding sites for transcription factors. We also note that the cooperation for a negative effect described here bears an analogy to transcriptional activation, where a promoter often cooperates with a remote enhancer.

Base Sequence↗
PubMed1996

Differential sensitivity of zinc finger transcription factors MTF-1, Sp1 and Krox-20 to CpG methylation of their binding sites.

Cytosine methylation at CpG sites is often negatively correlated with mammalian gene activity. Many transcription factors whose DNA binding site contains one or more CpG dinucleotides are no longer able to efficiently bind DNA when the site is methylated. A notable exception is the zinc finger factor Sp1 which binds DNA and activates transcription even when its binding site is methylated. Here we show that two other zinc finger factors, MTF-1 and Krox-20, can also bind to CpG methylated sites. MTF-1 regulates metallothionein gene transcription by binding to a number of metal responsive elements (MREs), and Krox-20 regulates Hox genes during hindbrain segmentation. However, a refined analysis of MTF-1/MRE binding shows that methylation is not tolerated at every binding site: the highest affinity site in the mouse metallothionein I gene, MREd, is unaffected by methylation, while two other MRE sites with CpGs at different positions are rendered partially or completely nonfunctional by methylation. Both methylation sensitive and insensitive factors/binding sites are likely to determine the developmental expression pattern of a gene.

Animals↗
PubMed1995

A transcriptional repressor obtained by alternative translation of a trinucleotide repeat.

Triplet nucleotide repeats are ubiquitous and rapidly evolving sequences in eucaryotic genomes. They are sporadically found in coding regions of transcription regulators where they become translated in different homopolymeric aminoacid (HPAA) stretches, depending on the local frame. Poly(CAG) yields three different HPAAs (poly Gln, Ser or Ala). Current sequence databases indicate a clear bias in the size and frequency of these HPAAs according to the rule: (Gln)n > (Ser)n >> (Ala)n. Aiming to understand the reasons of this bias, we changed the translational reading frame of the highly polymorphic CAG-repeat that normally encodes poly-Gln in the N-terminal portion of the rat glucocorticoid receptor (GR). The GR mutant in which the CAG repeat is translated to poly-Ala (called GR[Ala]) is incapable of transactivation, but maintains competence for hormone binding, nuclear translocation and specific DNA binding. We show that GR desactivation is obtained only when a very precise threshold length of the repeat is reached. GR[Ala] displays a strong negative dominance when tested for transcriptional activation in vivo and may become useful for selective competition of receptor dependent activities in tissue culture cells and transgenic animals. We discuss the implications of our findings for the understanding of the evolutionary behaviour of trinucleotide repeats in coding sequences.

Amino Acid Sequence↗
PubMed1995

Acinar and cellular distribution and mRNA expression of the epidermal growth factor receptor are changed during liver regeneration.

The epidermal growth factor receptor shows acinar heterogeneity with a portal-to-central concentration gradient. Immunohistochemical analysis showed that the strong cytoplasmic staining for epidermal growth factor receptor found in normal hepatocytes disappears over time after partial hepatectomy or sham operation, however, with different time courses. Four hours after surgery, 84.3 +/- 3.5% (mean +/- SD) of the hepatocytes in animals after sham operation showed strong cytoplasmic staining vs. 21.8 +/- 19.0% in animals after partial hepatectomy. After 12 h, the cytoplasmic staining in animals after sham operation was further reduced to 39.0 +/- 22.6% vs. 20.0 +/- 5.5% in animals after partial hepatectomy. At the same time point, we found staining for the epidermal growth factor receptor in nuclei of 21.8 +/- 14.8% and 3.0 +/- 3.9% of the hepatocytes in animals after partial hepatectomy and animals after sham operation, respectively. Northern blot analysis revealed comparable changes in expression of the epidermal growth factor receptor mRNA in animals after partial hepatectomy and in animals after sham operation. No changes were evident in animals after sham operation, however, if the abdominal incisions were shortened. This suggests that at least part of the changes found in animals with sham operation are due to acute phase events and/or surgical stress. In conclusion, partial hepatectomy induces changes in the intracellular and acinar fate of the epidermal growth factor receptor, drives the receptor to the nuclei, and affects the expression of the epidermal growth factor receptor mRNA.

Animals↗
PubMed1994

Effect of cyclodextrins and undigested starch on the loss of chenodeoxycholate in the faeces.

Starch that escapes digestion in the small intestine increases the elimination of chenodeoxycholate and its metabolites in the faeces of both mice and hamsters. In contrast, the elimination of cholate and its metabolites is not increased. In vitro, the affinity of starch for chenodeoxycholate is about 90-fold greater than for cholate. beta-Cyclodextrin, which approximates to one turn of the helical structures formed by the 1,4-linked glucose units of starch, shares these properties. It is proposed that these helical structures in starch act as binding sites for bile salts.

Animals↗
PubMed1994

Transcriptional activation modulated by homopolymeric glutamine and proline stretches.

Many transcription factors contain proline- or glutamine-rich activation domains. Here it is shown that simple homopolymeric stretches of these amino acids can activate transcription when fused to the DNA binding domain of GAL4 factor. In vitro, activity increased with polymer length, whereas in cell transfection assays maximal activity was achieved by 10 to 30 glutamines or about 10 prolines. Similar results were obtained when glutamine stretches were placed within a [GAL4]-VP16 chimeric protein. Because these stretches are encoded by rapidly evolving triplet repeats (microsatellites), they may be the main cause for modulation of transcription factor activity and thus result in subtle or overt genomic effects.

Amino Acid Sequence↗
PubMed1994

Identification of genes encoding zinc finger proteins, non-histone chromosomal HMG protein homologue, and a putative GTP phosphohydrolase in the genome of Chilo iridescent virus.

Five RNA transcripts of about 1.2 to 1.7 kilobases were mapped to a part of the genome of insect iridescent virus type 6 (Chilo iridescent virus; CIV) between genome coordinates 0.832 and 0.856 within the EcoRI DNA fragment F. The nucleotide sequence of this particular region (5702 base pairs) of the CIV genome was determined. The DNA sequence contains a number of perfect direct, inverted, and palindromic repeats including three clusters of tandemly organized repetitive DNA elements located between the nucleotide positions 1534 to 1566, 3720 to 3780, and 4350 to 4450. Eight long open reading frames (ORFs; EF1 to 8) were detected in the sequenced region of the CIV genome. ORF EF1 encodes a putative protein of 221 amino acid residues (aa) that is closely related to eukaryotic nonhistone chromosomal proteins of the high mobility group (HMG) superfamily. Virus encoded homologues of HMG proteins have not been reported so far. The EF2 gene product (145 aa) contains a specific zinc finger motif and belongs to a distinct group of identified and putative zinc finger proteins including a second putative protein (239 aa) of CIV encoded in the EcoRI DNA fragment Y (1984 bp; 0.381 to 0.391 viral map units). The product of EF6 (127 aa) is related to D250 ORF product of African swine fever virus (ASFV) and belongs to the recently described protein family sharing a highly conserved sequence motif with bacterial antimutator GTP phosphohydrolase MutT. Thus the sequenced region of the CIV genome encodes three putative proteins which may be directly involved in the replication and/or transcription of the viral DNA.

Amino Acid Sequence↗
PubMed1994

Effect of ATP, carbachol and other agonists on intracellular calcium activity and membrane voltage of pancreatic ducts.

The pancreatic duct has been regarded as a typical cAMP-regulated epithelium, and our knowledge about its Ca2+ homeostasis is limited. Hence, we studied the regulation of intracellular calcium, [Ca2+]i, in perfused rat pancreatic ducts using the Ca(2+)-sensitive probe fura-2. In some experiments we also measured the basolateral membrane voltage, Vbl, of individual cells. The resting basal [Ca2+]i was relatively high, corresponding to 263 +/- 28 nmol/l, and it decreased rapidly to 106 +/- 28 nmol/l after removal of Ca2+ from the bathing medium (n = 31). Carbachol increased [Ca2+]i in a concentration-dependent manner. At 10 mumol/l the fura-2 fluorescence ratio increased by 0.49 +/- 0.06 (n = 24), corresponding to an increase in [Ca2+]i by 111 +/- 15 nmol/l (n = 17). ATP, added to the basolateral side at 0.1 mmol/l and 1 mmol/l, increased the fluorescence ratio by 0.67 +/- 0.06 and 1.01 +/- 14 (n = 46; 12), corresponding to a [Ca2+]i increase of 136 +/- 22 nmol/l and 294 +/- 73 nmol/l respectively (n = 15; 10). Microelectrode measurements showed that ATP (0.1 mmol/l) hyperpolarized Vbl from -62 +/- 3 mV to -70 +/- 3 mV, an effect which was in some cases only transient (n = 7). This effect of ATP was different from that of carbachol, which depolarized Vbl. Applied together with secretin, ATP delayed the secretin-induced depolarization and prolonged the initial hyperpolarization of Vbl (n = 4). Several other putative agonists of pancreatic HCO3- secretion were also tested for their effects on [Ca2+]i.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1994

Active, interactive, and inactive steroid receptor mutants.

In transient co-transfection assays, there is extensive cross-interaction between glucocorticoid receptor (GR) domains. For example, mutation of the conserved Ile residue at position 484 (rat GR map) to cysteine allows a net separation of transactivation and DNA binding. We also observed that the ligand binding domain plays a key role in cooperative transactivation. Furthermore, some carboxy-located mutations markedly alter the response of GR to agonists and antagonists. Finally, different reading frames of the CAG repeat that normally produces an amino-located poly-Gln repeat profoundly affect GR transactivation without altering DNA or ligand binding. This trans-dominant negative phenotype, seen when the CAG repeat yields a poly-Ala stretch, may turn out to be an excellent tool for functional analysis of GR in transgenic organisms.

Amino Acid Sequence↗
PubMed1994

Factors that bind to RNA polymerase I promoter sequences of Trypanosoma brucei.

The procyclic acidic repetitive protein (procyclin) and variant surface glycoprotein genes of Trypanosoma brucei are transcribed by a polymerase sharing many features with RNA polymerase I. Mutational analyses on the PARP and ribosomal RNA promoters have shown that sequences important for promoter activity are concentrated 20-60 bp upstream of the transcription initiation site. The results of gel mobility shift assays using synthetic oligonucleotides spanning of these regions indicated the presence in trypanosomal extracts of factors capable of binding each promoter in a highly specific fashion. There was no evidence that the PARP, VSG and rRNA promoter fragments bound the same factor.

Animals↗
PubMed1994

Hierarchies of RNA-processing signals in a trypanosome surface antigen mRNA precursor.

Nearly all trypanosome mRNAs are synthesized as polycistronic precursors, from which mature mRNAs are excised by trans splicing and polyadenylation. Polyadenylation of a procyclic acidic repetitive protein (PARP, or procyclin) transcript was studied by transient transfection of constructs bearing a chloramphenicol acetyltransferase gene linked to the PARP intergenic region. Polyadenylation usually occurred at A residues, about 100 bases upstream of a trans-splicing acceptor signal. The wild-type polyadenylation site has a cryptic trans-splicing signal about 100 bp downstream: deletion or inversion of this signal results in polyadenylation at multiple sites, upstream of other cryptic trans-splicing signals. The PARP mRNA precursor appears to contain a hierarchy of possible processing signals, the function of cryptic ones being revealed only when the dominant ones are deleted or moved. Correct polyadenylation can be restored by addition of trans-splicing signals from other loci. The results indicate that polyadenylation is coupled to downstream trans splicing but that the products of the trans-splicing reaction are not necessarily functional mRNAs.

Animals↗