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Biomedical subjects

E Scheer

Publications and source records attributed to E Scheer.

At least 19 recordsLinked to original sources

Proximity effect and multiple Andreev reflections in gold atomic contacts.

We investigate the electronic transport properties of gold point contacts with superconducting aluminum leads. The modifications induced by the proximity effect in the quasiparticle density of states at the contact region are measured by tunnel spectroscopy. The theory of transport through multiple Andreev reflections is extended to incorporate these effects and used to determine the number and transmission coefficients of the conduction channels in the contact regime. We find that the smallest contacts, formed by one gold atom between the electrodes, contribute one single channel to the transport with variable transmission T between 0.1 and 1.

Journal Article↗

Identification of hTAF(II)80 delta links apoptotic signaling pathways to transcription factor TFIID function.

Apoptotic cell death is associated with altered levels of mRNA expression, yet the mechanisms that coordinate changes in gene expression with activation of the cell death machinery remain obscure. Here, we report the cloning and characterization of hTAF(II)80 delta, a specialized isoform of the general transcription factor TFIID subunit hTAF(II)80. Several distinct apoptotic stimuli induce the expression and caspase-dependent cleavage of hTAF(II)80 delta. hTAF(II)80 delta, unlike hTAF(II)80, forms a TFIID-like complex lacking hTAF(II)31. Elevated expression of hTAF(II)80 delta in HeLa cells is sufficient to trigger apoptotic cell death and selectively alters cellular transcription, including the induction of the target genes gadd45 and p21. These data define a signaling pathway that couples apoptotic signals to a reprogramming of RNA polymerase II transcription.

Amino Acid Sequence↗

Mammalian TAF(II)30 is required for cell cycle progression and specific cellular differentiation programmes.

The two alleles of the 30 kDa TATA-binding protein associated factor (TAF(II)30) gene, have been targeted by homologous recombination in murine F9 embryonal carcinoma cells and subsequently disrupted using a Cre recombinase-loxP strategy. The TAF(II)30-null cells are not viable, but are rescued by the expression of human TAF(II)30. Cells lacking TAF(II)30 are blocked in G(1)/G(0) phase of the cell cycle and undergo apoptosis. In agreement with the G(1) arrest phenotype, the expression of cyclin E is impaired and the retinoblastoma protein is hypophosphorylated in the TAF(II)30-null cells. Interestingly, retinoic acid (RA) treatment prevented TAF(II)30-null cell death and induced primitive endodermal differentiation. In contrast, the RA- and cAMP-induced parietal endodermal differentiation was impaired in the TAF(II)30-null cells. Thus, TAF(II)30 is not indispensable for class II gene transcription in general, but seems to be required for the expression of a subset of genes.

Animals↗

Organization and chromosomal localization of the gene (TAF2H) encoding the human TBP-associated factor II 30 (TAFII30).

The basal RNA polymerase II transcription factor, TFIID, is composed of the TATA binding protein (TBP) and 8-13 TBP-associated factors (TAFs) ranging from 250 to 17 kDa. The structure of the human gene encoding the 30-kDa subunit of TFIID, TAF2H, has been determined. The gene consists of five exons (ranging from 66 to 248 bp) and four introns (ranging from 83 to 211 bp). The transcription start site of the mRNA was mapped, and it shares a weak homology to the consensus of known initiator elements. Using in situ hybridization on human metaphase chromosomes, the TAF2H gene has been localized in the 11p15.2-p15.5 region of the human genome.

Amino Acid Sequence↗

Different TBP-associated factors are required for mediating the stimulation of transcription in vitro by the acidic transactivator GAL-VP16 and the two nonacidic activation functions of the estrogen receptor.

The estrogen receptor (ER) contains two nonacidic transcriptional activation functions, AF-1 and AF-2 (formerly TAF-1 and TAF-2). In this study we show that AF-1 and AF-2 are able to stimulate transcription in vitro in a HeLa cell system when fused to the DNA binding domain of the yeast activator GAL4. We also demonstrate that a factor(s) required for the function of the ER AFs is chromatographically separable from a factor(s) necessary for the activity of the acidic activation domain of VP16. Moreover, immunoprecipitation experiments using a monoclonal antibody directed against the TATA box binding protein (TBP) indicate, that these different factors are associated with TBP in distinct TFIID complexes.

Amino Acid Sequence↗

Occupational-type exposure tests and bronchoalveolar lavage analyses in two patients with byssinosis and two asymptomatic cotton workers.

Two workers suffering from stage III byssinosis and claiming for compensation were examined. Bronchial obstruction was present in one case. MEF25-75 values were significantly reduced and bronchial hyperreactivity was present in both subjects. Occupational-type exposure tests with cotton dust resulted in significant decreases in arterial oxygen pressure for more than 2 h and were associated with an obstructive ventilation pattern in one of the patients. Prolonged hypoxemia which is not paralleled by lung function changes is probably typical for byssinosis patients since we have never seen this in inhalative challenge tests with various environmental antigens and other occupational substances including flour dust. No specific IgE or IgG antibodies could be detected. In the two patients a hitherto unknown significant increase in CD23+ lymphocytes and granulocytosis were detected by bronchoalveolar lavage (BAL). Corresponding investigations in two cotton workers without any evidence of byssinosis revealed neither lung function changes after the exposure test nor striking BAL findings. Our results demonstrate the diagnostic value of specific challenge tests and BAL investigations in patients suffering from byssinosis, which is often difficult to diagnose.

Adult↗

Increased incidence of anti-dsDNA autoantibody concentration in sera of workers occupationally exposed to diisocyanates.

Sera of 87 industrial workers with a history of occupational exposition to various diisocyanates, toluene diisocyanate, hexamethylene diisocyanate and methylene-diphenyl diisocyanate were analyzed for antibodies to isocyanate-conjugated human serum albumin and for anti-dsDNA autoantibodies. Ten workers (approx. 11%) were shown to have elevated anti-dsDNA autoantibody concentrations and 13 revealed antibodies to isocyanate-modified human serum albumin. The overlap of both tests being positive was calculated at about 40%. It would seem, therefore, that routine estimation of anti-dsDNA autoantibodies could provide additional useful information for the clinical diagnosis of occupational health impairment due to isocyanate exposure.

Adult↗

[Extensive pulmonary tumor embolisms of anaplastic thyroid gland carcinoma as a rare cause of hemorrhagic pleural effusion in an 88-year-old patient].

An 88 year old woman without substantial previous illness was admitted to hospital because of a rapidly developing dyspnea and thoracic pains. X-Ray, CT scan and ultra sound showed a subdivided pleural effusion of the left side. After a short time a pulmonary infiltrate as well as a contralateral pleural effusion developed. Neither tumor cells nor mycobacteria could be detected in repeated pleural punctions. The general condition of the patient was deteriorating continuously while an antibiotic therapy given in the meantime only led to a temporary recovery. Three weeks later the patient died under the picture of a cardio-respiratory failure. At autopsy the lungs showed parenchymal haemorrhages and multiple infarctions as well as pleural effusions. The above mentioned changes could be explained histologically by tumor embolism of small pulmonary arteries from an anaplastic thyroid carcinoma. The discussion gives a short survey about already published cases of tumor embolism in the lung. PMVC as the diagnostic method of choice is discussed.

Aged↗

Distinct classes of transcriptional activating domains function by different mechanisms.

We have previously shown that the two transcriptional activation functions (TAF-1 and TAF-2) of the human estrogen receptor (hER) have synergistic properties different from one another and from those of acidic activating domains (AADs). Here we compare the transcriptional interference/squelching properties of the hER TAFs with those of the AADs of yeast GAL4 and chimeric GAL-VP16 activators. Our results indicate that AADs interact with a factor(s) that, while required for activation by AADs, is not essential for activation by hER TAFs. In contrast, hER TAFs appear to interact with factors indispensable for mediating both their activation function and that of AADs. Thus, different classes of trans-activators may interact with different factors. In addition, the synergistic and transcriptional interference/squelching properties of the two TAFs of the human glucocorticoid receptor (hGR) indicate that both are composed of acidic and nonacidic activation functions.

Base Sequence↗

The human estrogen receptor has two independent nonacidic transcriptional activation functions.

We have previously reported the presence of a hormone-inducible transcriptional activation function (TAF-2) within the region of the estrogen receptor (ER) that contains the hormone binding domain. We show here that the N-terminal A/B region of the ER contains an independent constitutive activation function (TAF-1) that exhibits cell type specificity since it activates transcription efficiently in chicken embryo fibroblasts, but only poorly in HeLa cells. By analyzing the ability of TAF-1, TAF-2, and the GAL4 and VP16 acidic activating domains (AADs) to homosynergize and heterosynergize with one another and with the factor binding to the upstream element (UE) of the adenovirus 2 major late promoter, we show that the activation properties of TAF-1 and TAF-2 are different and distinct from those of AADs, in agreement with the absence of acidic amino acid stretches in TAF-1 and TAF-2.

Animals↗

Action of substance P and an analogue on blood pressure and avoidance learning in rats with spontaneous hypertension (SHR).

Substance P (SP) and an analogue (Lys-Phe-Ile-Gly-Leu-MetNH2 = EH) were tested in acute experiments on the blood pressure in the intact rat anaesthetized with urethane. A biphasic response, consisting of an initial depressor, followed by a pressor component, was seen. In low concentrations, SP decreases blood pressure, in medium concentrations SP produces a pronounced biphasic response, in high concentrations SP produces only hypertensive reactions. In chronic experiments, SP-peptides act also in different directions. After EH, disorders in avoidance learning were completely eliminated from 10 weeks old spontaneously hypertensive rats (SHR) or conditionally from SHR age 14 or 26 weeks. Elevated blood pressure in SHR aged 26 weeks was reduced by EH. Blood pressure in SHR aged 14 weeks was almost unaffected by EH and blood pressure went up in ten weeks old SHR. SP had a weaker action in comparison with EH. These results are in agreement with the hypothesis proposed by Oehme and co-workers [11-13] that SP can act as a regulatory peptide (="regulide").

Animals↗

Cell walls of Coccidioides immitis: neutral sugars of aqueous alkaline extract polymers.

The neutral sugar components of hydrolysates of the alkali-soluble and -insoluble fractions of an acid-extracted Coccidioides immitis mycelial cell wall preparation were examined by gas-liquid chromatography. The alkali-soluble fraction was separated into a neutral water-soluble (46% carbohydrate) and a neutral water-insoluble fraction (6% carbohydrate). Glucose was the major neutral sugar constituent of all fractions. Mannose appeared to be a second major component of the alkali-soluble, water-soluble fraction. 3-O-methylmannose was absent. Small amounts of other sugars, including galactose and pentoses, were tentatively identified. Borohydride reduction before alkaline extraction resulted in retention of almost half of the glucose and variable amounts of other components in the alkaline residue, indicating that solubilization of cell wall polymers by alkaline extraction results in significant degradation of the native cell wall polymers.

Cell Fractionation↗

[Inhibition of 3-H-noradrenalin uptake in synaptosomes by substance P].

The uptake kinetics of DL-[3H]-norepinephrine into synaptosomes from rat brain hypothalamus can be described as a two stage process with uptake constants of Km = 0.9 micron and Km = 0.06 micron, respectively. Substance P exerts an inhibiting influence on both uptakes. The possible importance of this inhibition for the regulation of noradrenergic transmission is discussed.

Animals↗