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A Sailer

Publications and source records attributed to A Sailer.

29 records · Page 2Linked to original sources
PubMed1994

PrP-deficient mice are resistant to scrapie.

Prusiner proposed that the infectious agent of scrapie, the prion, is PrPSc, a modified form of the normal host protein PrPC. Prn-p0/0 mice devoid of PrPC showed normal development and behavior. When inoculated with mouse scrapie prions they remained free of scrapie symptoms for at least 16 months while wild type controls all died within 6 months. Propagation of infectivity in the PrP null mice, if any, was less than 10(-5) that in wild type animals. Surprisingly, heterozygous Prn-p0/+ mice also showed enhanced resistance to scrapie. After introduction of Syrian hamster PrP transgenes, Prn-p0/0 mice became highly susceptible to hamster but not to mouse prions. These experiments show that PrPC, possibly at close to normal levels, is required for the usual susceptibility to scrapie and that lack of homology between incoming prions and the host's PrP genes retards disease.

Animals↗
PubMed1994

High prion and PrPSc levels but delayed onset of disease in scrapie-inoculated mice heterozygous for a disrupted PrP gene.

BACKGROUND: It has been proposed that the prion, the infectious agent of transmissible spongiform encephalopathies, is PrPSc, a post-translationally modified form of the normal host protein PrPC. We showed previously that mice devoid of PrPC (Prn-p0/0) are completely resistant to scrapie. We now report on the unexpected response of heterozygous (Prn-p0/+) mice to scrapie infection. MATERIALS AND METHODS: Prn-p0/+, Prn-p0/0 and Prn-p+/+ mice were obtained from crosses of Prn-p0/+ mice. Mice were inoculated intracerebrally with mouse-adapted scrapie agent and the clinical progression of the disease recorded. Mice were sacrificed at intervals, PrPSc was determined as protease-resistant PrP and the prion titer by the incubation time assay. RESULTS: Prn-p0/+ mice, which have about half the normal level of PrPC in their brains, show enhanced resistance to scrapie, as manifested by a significant delay in onset and progression of clinical disease. However, while in wild type animals an increase in prion titer and PrPSc levels is followed within weeks by scrapie symptoms and death, heterozygous Prn-p0/+ mice remain free of symptoms for many months despite similar levels of scrapie infectivity and PrPSc. CONCLUSIONS: Our findings extend previous reports showing an inverse relationship between PrP expression level and incubation time for scrapie. However, contrary to expectation, overall accumulation of PrPSc and prions to a high level do not necessarily lead to clinical disease. These findings raise the question whether high titers of prion infectivity could also persist for long periods under natural circumstances in the absence of clinical symptoms.

Animals↗
PubMed1993

Mice devoid of PrP are resistant to scrapie.

S.B. Prusiner proposed that the infectious agent of scraple, the prion, is PrPSc, a modified form of the normal host protein PrPC. Prn-p0/0 mice devoid of PrPC showed normal development and behavior. When inoculated with mouse scrapie prions, they remained free of scrapie symptoms for at least 13 months while wild-type controls all died within 6 months. Surprisingly, heterozygous Prn-p0/+ mice also showed enhanced resistance to scrapie. After introduction of Syrian hamster PrP transgenes, Prn-p0/0 mice became highly susceptible to hamster but not to mouse prions. These experiments show that PrPC, possibly at close to normal levels, is required for the usual susceptibility to scrapie and that lack of homology between incoming prions and the host's PrP genes retards disease.

Animals↗
PubMed1992

Interferon regulatory factor-1 (IRF-1) activates the synthetic IRF-1-responsive sequence (GAAAGT)4 in Saccharomyces cerevisiae.

In appropriate mammalian cells, interferon regulatory factor-1 (IRF-1) can activate the virus-responsive element of the IFN-beta promoter (VRE beta") or the synthetic oligonucleotide (GAAAGT)4. The latter contains two copies of the functional equivalent of PRDI, one of the regulatory domains of VRE beta". We prepared yeast strains containing an IRF-1 expression plasmid under the control of the galactose-inducible Gal1 promoter and a reporter plasmid with either (GAAAGT)4, VRE beta", or other test sequences placed upstream of a minimal promoter linked to the beta-galactosidase coding sequence. Upon induction of IRF-1 expression, the (GAAAGT)4-containing promoter was activated, but VRE beta" and all other sequences tested were inactive. Our results showed that IRF-1 belongs to a class of higher eukaryotic transcription factors that can interact with the yeast transcriptional machinery. Our findings also raised the question why the duplicate PRDI-like sequences in (GAAAGT)4 can be activated by IRF-1 synthesized in yeast, but not VRE beta", which also contains at least two PRDI-like sequences.

Base Sequence↗
PubMed1979

[Investigations on combined injuries, 26th communication: investigations on the changes in the state of resistance following sublethal whole-body irradiation (author's transl)].

The risk of a bacterial invasion by pseudomonas, e. coli, proteus, citrobacter and gaffkya via an open skin wound was investigated in combined injured mice (infliction of a skin wound and irradiations). Suspensions of different bacterial strains were applied on the wound and then the lethality was determined. Besides of apathogenic (citrobacter, proteus, gaffkya) and high pathogenic bacteria (e. coli and pseudomonas) an e. coli strain of the 0-Group 81 was found that seems to induce a decrease of lethality even after sublethal whole body irradiation.

Animals↗
PubMedDate not supplied

Vascular endothelial growth factor (VEGF) and VEGF receptors in diabetic nephropathy: expression studies in biopsies of type 2 diabetic patients.

Vascular endothelial growth factor (VEGF) is involved in the pathogenesis of diabetic retinopathy but its role in diabetic nephropathy is only speculative so far. It has been shown that in renal cortex of normal kidneys, glomerular and tubular epithelial cells express VEGF and that VEGF 165 is the predominant isoform. Two VEGF receptors, KDR (kinase domain region) and Flt-1 (fms-like tyrosine kinase) are co-expressed by glomerular and peritubular capillary endothelial cells. However, VEGF and VEGF receptors are predominantly expressed at glomerular level. We recently demonstrated that in type 2 diabetic patients glomerular qualitative and quantitative changes of VEGF mRNA expression are associated with functional and structural renal changes. In the present work we focused on the tubulo-interstitial compartment; by reverse transcription/polymerase chain reaction (RT/PCR) we evaluated the expression of VEGF, KDR, Flt-1 and the relationship between the two main type of VEGF isoforms, VEGF121 and VEGF165 in the tubulo-interstitium of type 2 diabetic patients. Patients were divided in three category on the basis of renal structure pattern: CI, with normal or near normal renal structure; CII, with glomerular and tubulo-interstitial lesions occurring in parallel (typical diabetic nephropathology); CIII, with atypical pattern of renal injury, i.e., more severe tubulo-interstitial and vascular than glomerular changes. Comparison between the two cortical compartments revealed that, both in glomeruli and in tubulo-interstitium. VEGF121 isoform exceed VEGF165 while Flt-1 was significantly lower in glomeruli. CIII patients had the lowest tubulo-interstitial level of VEGF and Flt-1 mRNAs. These results suggest that the transcriptional shifting from VEGF165 to VEGF121 isoform and the unbalanced FIt-1 expression between tubulo-interstitium and glomeruli could be involved in the pathogenesis of diabetic nephropathy. Furthermore, at least in CIII patients, down-regulation of the VEGF-Flt-1 system could be involved in the mechanisms leading to tubulointerstitial diabetic lesions.

Adult↗
PubMedDate not supplied

Differentiation-related p53 protein expression in nondysplastic sinonasal inverted papillomas.

To clarify p53 protein expression in nondysplastic sinonasal inverted papillomas, archived surgical specimens from 19 patients were studied using immunohistochemistry. Staining results were compared between inverted papillomas and adjacent, nonpapillomatous nasal mucosa. Further, immunoreactivity was compared between columnar (respiratory), transitional (cuboidal), and squamous epithelium in inverted papillomas. Positive staining was found in 17 of 19 inverted papillomas (89%). Immunoreactivity involved predominantly basal and parabasal cells and was either comparable or higher in inverted papillomas compared with adjacent mucosa. In 65% of immunoreactive inverted papillomas comparable staining results were seen between columnar (respiratory), transitional (cuboidal), and squamous epithelium. In 35% of p53 protein-positive inverted papillomas, enhanced immunoreactivity was observed in transitional (cuboidal) and squamous epithelium compared with columnar (respiratory) epithelium. Within these cases, immunoreactivity was either comparable or higher in squamous compared with transitional (cuboidal) epithelium. Conclusively, the expression of p53 protein is present in 89% of nondysplastic sinonasal inverted papillomas and also involves the adjacent, nonpapillomatous nasal mucosa. A tendency toward increasing p53 protein expression from nonpapillomatous nasal mucosa to inverted papilloma as well as along the metaplastic process from columnar (respiratory) to transitional (cuboidal) and finally squamous epithelium within inverted papillomas can be postulated.

Adult↗