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U Hansen

Publications and source records attributed to U Hansen.

At least 37 records · Page 2Linked to original sources
PubMed1997

Kinetic analysis of Ca2+/K+ selectivity of an ion channel by single-binding-site models.

Current-voltage relationships of a cation channel in the tonoplast of Beta vulgaris, as recorded in solutions with different activities of Ca2+ and K+ (from Johannes & Sanders 1995, J. Membrane Biol. 146:211-224), have been reevaluated for Ca2+/K+ selectivity. Since conversion of reversal voltages to permeability ratios by constant field equations is expected to fail because different ions do not move independently through a channel, the data have been analyzed with kinetic channel models instead. Since recent structural information on K+ channels show one short and predominant constriction, selectivity models with only one binding site are assumed here to reflect this region kinetically. The rigid-pore model with a main binding site between two energy barriers (nine free parameters) had intrinsic problems to describe the observed current-saturation at large (negative) voltages. The alternative, dynamic-pore model uses a selectivity filter in which the binding site alternates its orientation (empty, or occupied by either Ca2+ or K+) between the cytoplasmic side and the luminal side within a fraction of the electrical distance and in a rate-limiting fashion. Fits with this model describe the data well. The fits yield about a 10% electrical distance of the selectivity filter, located about 5% more cytoplasmic than the electrical center. For K+ translocation, reorientation of the unoccupied binding site (with a preference of about 6:5 to face the lumenal side) is rate limiting. For Ca2+, the results show high affinity to the binding site and low translocation rates (<1% of the K+ translocation rate). With the fitted model Ca2+ entry through the open channel has been calculated for physiological conditions. The model predicts a unitary open channel current of about 100 fA which is insensitive to cytoplasmic Ca2+ concentrations (between 0.1 and 1 microM) and which shows little sensitivity to the voltage across the tonoplast.

Binding Sites↗
PubMed1997

Mitogenic stimulation of resting T cells causes rapid phosphorylation of the transcription factor LSF and increased DNA-binding activity.

The mammalian transcription factor LSF (CP2/LBP-1c) binds cellular promoters modulated by cell growth signals. We demonstrate here that LSF-DNA-binding activity is strikingly regulated by induction of cell growth in human peripheral T lymphocytes. Within 15 min of mitogenic stimulation of these cells, the level of LSF-DNA-binding activity increased by a factor of five. The level of LSF protein in the nucleus remained constant throughout this interval. However, a rapid decrease in the electrophoretic mobility of LSF, attributable to phosphorylation, correlated with the increase in DNA-binding activity. pp44 (ERK1) phosphorylated LSF in vitro on the same residue that was phosphorylated in vivo, specifically at amino acid position 291, as indicated by mutant analysis. As direct verification of the causal relationship between phosphorylation and DNA-binding activity, treatment in vitro of LSF with phosphatase both increased the electrophoretic mobility of the protein and decreased LSF-DNA-binding activity. This modulation of LSF-DNA-binding activity as T cells progress from a resting to a replicating state reveals that LSF activity is regulated during cell growth and suggests that LSF regulates growth-responsive promoters.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1997

[Clinical effect of ranitidine in psoriasis. An open prospective study].

We report the results of an open, prospective study of 20 patients with moderate to severe psoriasis (median PASI score: 15.7) treated with oral ranitidine 300 mg twice daily for six months. No other medication was allowed during the study period. The median PASI score was reduced to 14.5, 9.1 and 5.7 after one, three and six months of treatment, respectively (p < 0.00001). A mild to moderate worsening was observed in 15 patients within the first month of treatment, but this was not followed by exclusion from the study, and long-term treatment improved disease status in most patients. Eight patients continued therapy with ranitidine 300 mg twice daily after the study was completed. None of these patients relapsed during a follow-up period of 12-18 months. The results of the present study suggest that ranitidine may be beneficial in the treatment of some patients with psoriasis.

Adult↗
PubMed1997

MR diffusion imaging of human intracranial tumours.

We used MRI for in vivo measurement of brain water self-diffusion in patients with intracranial tumours. The study included 28 patients (12 with high-grade and 3 with low-grade gliomas, 7 with metastases, 5 with meningiomas and 1 with a cerebral abscess). Apparent diffusion coefficients (ADC) were calculated in a single axial slice through the tumours, the sequence was sensitive to diffusion along the cephalocaudal axis. Our main finding was that ADC in contrast-enhancing areas within cerebral metastases was statistically significantly higher than ADC in contrast-enhancing areas in high-grade gliomas (P < or = 0.05). Furthermore, the ADC in oedema surrounding metastases were statistically significantly higher the ADC in oedema around high-grade gliomas (P < or = 0.02). The ADC in patients with meningiomas did not differ significantly from those seen with high-grade gliomas or cerebral metastases. The highest ADC were found within cystic or necrotic tumour areas. In one patient with a cerebral abscess, suspected of having a high-grade glioma, the ADC was similar to that in high-grade gliomas. The finding of higher ADC in cerebral metastases than in high-grade gliomas may be helpful in trying to distinguish between these tumours preoperatively; it suggests increased free extracellular and/or intracellular water fraction in cerebral metastases. The method seems to hold potential for further noninvasive characterisation of intracranial tumours.

Adult↗
PubMed1997

Expression of CuZn- and Mn-superoxide dismutase in human colorectal neoplasms.

Decreased intracellular SOD protein levels and activity have been related with malignancy in the past. To investigate their relevance in the carcinogenetic process in the colon, we determined quantitatively CuZn-SOD and Mn-SOD levels and total SOD activity by histochemical means in human normal colorectal mucosa, adenomas, and carcinomas. Protein levels and activity were significantly decreased in carcinomas. CuZn-SOD protein levels, but not Mn-SOD levels or total SOD activity were related with differentiation grade and to a lesser extent with Dukes stage. Moderately differentiated carcinomas and Dukes stage A carcinomas showed lowest levels. Some carcinomas expressed elevated levels of CuZn-SOD and this was an indication of poor survival. It is concluded that decreased SOD expression is not a prognostic marker and seems to be a secondary phenomenon rather than directly linked with the carcinogenetic process.

Adenocarcinoma↗
PubMed1997

The homogeneity of hidradenitis suppurativa lesions. A histological study of intra-individual variation.

Recent data suggest that hidradenitis suppurative is a disease of the follicle, but the histological homogeneity of findings over time and in different anatomical regions has not been verified. Its description may help towards a better classification of the follicular diseases. Correct classification provides both knowledge by interference and a way of generalizing with respect to the significance of specific findings. The intra-individual variation of hidradenitis was described through classification of specimens taken from patients with multiple simultaneous or consecutive excisions. A total of 51 specimens from 11 patients were examined; of these 30 were from synchronous biopsies, and 21 from consecutive biopsies (range 2 months to 6 years). The majority of specimens (44/51) contained poral occlusion, sinus tracts or cysts. This pattern was present in 50-85% of the specimens from any given patient with hidradenitis. No primary apocrine involvement was seen. Fibrosis occurred often (33/51 specimens), and eccrine involvement was seen more often than apocrine involvement (10 vs 7 specimens). The homogeneous histology of hidradenitis supports its reclassification as a follicular disease. The reproducibility of the findings further suggests that the changes are specific and that hidradenitis is therefore a definite disease entity within the spectrum of follicular diseases. Additional functional studies may help classify hidradenitis more precisely in relation to other follicular diseases.

Adult↗
PubMed1997

Alleviation of histone H1-mediated transcriptional repression and chromatin compaction by the acidic activation region in chromosomal protein HMG-14.

Histone H1 promotes the generation of a condensed, transcriptionally inactive, higher-order chromatin structure. Consequently, histone H1 activity must be antagonized in order to convert chromatin to a transcriptionally competent, more extended structure. Using simian virus 40 minichromosomes as a model system, we now demonstrate that the nonhistone chromosomal protein HMG-14, which is known to preferentially associate with active chromatin, completely alleviates histone H1-mediated inhibition of transcription by RNA polymerase II. HMG-14 also partially disrupts histone H1-dependent compaction of chromatin. Both the transcriptional enhancement and chromatin-unfolding activities of HMG-14 are mediated through its acidic, C-terminal region. Strikingly, transcriptional and structural activities of HMG-14 are maintained upon replacement of the C-terminal fragment by acidic regions from either GAL4 or HMG-2. These data support the model that the acidic C terminus of HMG-14 is involved in unfolding higher-order chromatin structure to facilitate transcriptional activation of mammalian genes.

Amino Acid Sequence↗
PubMed1997

Two evolutionarily conserved repression domains in the Drosophila Kruppel protein differ in activator specificity.

To identify biologically functional regions in the product of the Drosophila melanogaster gene Kruppel, we cloned the Kruppel homolog from Drosophila virilis. Both the previously identified amino (N)-terminal repression region and the DNA-binding region of the D. virilis Kruppel protein are greater than 96% identical to those of the D. melanogaster Kruppel protein, demonstrating a selective pressure to maintain the integrity of each region during 60 million to 80 million years of evolution. An additional region in the carboxyl (C) terminus of Kruppel that was most highly conserved was examined further. A 42-amino-acid stretch within the conserved C-terminal region also encoded a transferable repression domain. The short, C-terminal repression region is a composite of three subregions of distinct amino acid composition, each containing a high proportion of either basic, proline, or acidic residues. Mutagenesis experiments demonstrated, unexpectedly, that the acidic residues contribute to repression function. Both the N-terminal and C-terminal repression regions were tested for the ability to affect transcription mediated by a variety of activator proteins. The N-terminal repression region was able to inhibit transcription in the presence of multiple activators. However, the C-terminal repression region inhibited transcription by only a subset of the activator proteins. The different activator specificities of the two regions suggest that they repress transcription by different mechanisms and may play distinct biological roles during Drosophila development.

Amino Acid Sequence↗
PubMed1996

Mechanisms of eukaryotic transcription: surfaces, complexes, and contexts. (Cold Spring Harbor Cancer Cells Meeting, August 30-September 3, 1995).

As with other biological processes, evolution has resulted in numerous, alternative pathways to achieve regulation of gene expression. In the elaborate series of steps required to transcribe a gene, necessitating assembly and subsequent disassembly of multiple complexes, subtle alterations in specific protein-protein interactions can lead to dramatically different transcriptional consequences.

Animals↗
PubMed1996

Active repression mechanisms of eukaryotic transcription repressors.

Regulators of transcription and, in particular, transcriptional repressors, play central roles in vital biological processes, such as development and the regulation of cell growth. A major class of transcriptional repressors consists of DNA-binding proteins that interact with specific promoter elements and repress transcription via small, portable repression 'domains'. Such transcriptional inhibition, first identified only five years ago, has been termed active repression, because it is not mediated simply by steric hindrance mechanisms. It is unknown how interaction(s) between such a repressor and the RNA polymerase II basal or regulatory transcription machinery can derail the formation or competency of a transcription complex at a promoter. However, the recent progress toward identification of molecular targets suggests several specific mechanisms for achieving active repression.

Amino Acid Sequence↗
PubMed1996

Electron microscopic study of possible sites of ultrafiltration in Lumbricus terrestris (Annelida, Oligochaeta).

Electron microscopic investigations of blood vessels of Lumbricus terrestris (L. terrestris) were conducted to show sites of filtration such as podocytes or irregular fenestrations. The endothelia of the blood vessels consist of myoendothelial cells, chloragocytes and podocytes. The podocytes form large archs over a considerable area of the vessels. Numerous small pedicels are presented on the lumen side and the gaps between adjacent pedicels are bridged by slit membranes. The podocytes are restricted to the front part of the ventral vessel. They are regarded as the structural basis for ultrafiltration. Additionally to the filtration site between ventral vessel and coelomic cavity, a second putative filtration site was found in the front part of the body between intestinal blood sinus and coelomic cavity. The endothelium of the sinus is formed by myoendothelial cells, pedicels and chloragocytes with footlike processes. In such areas the basement membrane is the only continous layer between blood vessel and coelomic cavity. The basement membrane of the blood vessels of L. terrestris is a characteristic association of three layers of different composition and thickness. Possible filtration sites in form of podocytes and irregular fenestrations could be localized at the border between the blood compartment and the coelomic compartment. Presumably the primary urine is formed by ultrafiltration of blood.

Animals↗
PubMed1996

Histology of hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa is traditionally classified as a disease of the apocrine gland. However, different histologic descriptions exist. OBJECTIVE: Our purpose was to describe prospectively the histopathologic characteristics of hidradenitis. METHODS: We systematically described and classified 60 consecutive biopsy specimens from patients with hidradenitis and compared them with 33 specimens from clinically noninvolved regional controls. RESULTS: A heterogeneous histologic picture was found. Apocrine glands were involved in a minority of the 60 specimens, 17 showed poral occlusion, 17 simple folliculitis without poral occlusion, 9 sinus tracts, 6 epithelial cyst, 5 abscess, 3 apocrinitis, 2 diffuse dermal inflammation, and 1 pyogenic granuloma and scarring. Secondary involvement of apocrine glands was found in 12% of all specimens, and secondary involvement of eccrine glands was found in 25%. Sinus tracts were found significantly more often in the presence of poral occlusion or epithelial cysts. Control specimens frequently revealed changes compatible with early stages of follicular involvement. Apocrine glands were observed significantly more often in the axillae than in the groin. CONCLUSION: The clinical picture of hidradenitis suppurativa covers a broad histologic spectrum. This may help explain the therapeutic problems posed by this disease. The disease appears to be predominantly follicular, and apocrine glands appear to be primarily involved in only a minority of axillary lesions.

Abscess↗
PubMed1995

Chemical and physiological characterization of taxa in the Fusarium sambucinum complex.

Forty-one isolates of Fusarium sambucinum sensu lato were screened for production of secondary metabolites in agar cultures. Of 16 strains of F. sambucinum sensu stricto all but two strains produced diacetoxyscirpenol and two unidentified metabolites, TB1 and TB2 respectively. The two remaining F. sambucinum strains produced T-2 toxin, TB1 and TB2. Fusarium venenotum (6 strains) produced diacetoxyscirpenol and an unidentified metabolite BB. Fusarium torulosum (8 strains) produced wortmannin and antibiotic Y. The three species could be differentiated by their pattern of identified and unidentified metabolites detected by agar plug TLC combined with chemical data from HPLC-diode array detection of fungal extracts, and data on growth rates on potato sucrose agar and tannin sucrose agar.

Androstadienes↗
PubMed1995

Systemic high-dose ranitidine in the treatment of psoriasis: an open prospective clinical trial.

We report the results of an open, prospective study on the efficacy of systemic ranitidine in the treatment of psoriasis. Twenty patients suffering from moderate to severe psoriasis were included in the study. The median pretreatment PASI score was 15.7 (range 6.0-24.7). The patients were treated with oral ranitidine 300 mg twice a day for 6 months; no other medication was allowed during the study period. Eighteen patients completed the study. The median PASI score was reduced from 15.7 to 14.5, 9.1 and 5.7, after 1, 3 and 6 months of treatment, respectively (P < 0.00001). A significant reduction in PASI score was evident at 3 months of treatment. A mild to moderate deterioration occurred in 15 patients within the first month of treatment, but this was followed by improvement during prolonged treatment in most patients. No other clinical and/or biochemical side-effects were observed. Eight patients continued therapy with ranitidine after the study was completed, and none of these patients relapsed during a follow-up period of 12-18 months. The results of the present study suggest that ranitidine may be a beneficial and safe treatment for psoriasis. In addition, high-dose, long-term ranitidine treatment appears to be free from severe adverse effects.

Administration, Oral↗
PubMed1995

A TEF-1-independent mechanism for activation of the simian virus 40 (SV40) late promoter by mutant SV40 large T antigens.

Simian virus 40 (SV40) large tumor antigen (T antigen) stimulates the activity of the SV40 late promoter and a number of cellular and other viral promoters. We have characterized the ability of T antigens with mutations in the DNA-binding domain and within the N-terminal 85 residues to activate the SV40 late promoter. T antigens lacking both nonspecific and sequence-specific DNA-binding activities were able to induce the late promoter. Mutations within the N-terminal 85 residues of T antigen diminished activation by less than twofold. Activation by wild-type and most of the mutant T antigens required intact binding sites for the cellular transcription factor TEF-1 in the late promoter. Curiously, two mutants altered in the N-terminal region and an additional mutant altered in the DNA-binding domain activated a late promoter derivative lacking TEF-1 binding sites, indicating the existence of a TEF-1-independent pathway for activation of the late promoter. A consensus binding site for the TATA binding protein, TBP, was created in variants of late promoters either containing or lacking TEF-1 binding sites. Basal expression was increased by the consensus TBP binding site only when TEF-1 binding sites were present, leading to a reduction in the degree of activation by T antigen. However, activation by a mutant T antigen of the promoter lacking TEF-1 sites was unchanged or slightly enhanced by the consensus TBP binding site. These results suggest that some mutant T antigens can stabilize an interaction between TBP and additional factors bound to the late promoter.

Antigens, Polyomavirus Transforming↗
PubMed1994

[Shock and coagulation disorders in systemic mastocytosis].

A 41-year-old man was admitted in circulatory shock of unknown aetiology (systolic pressure 50 mm Hg) and marked reddening of the upper part of the body as well as maculopapular rash over the whole body. After 1500 ml of colloidal solution had been infused the blood pressure rose to a level at which the patient's condition was no longer at risk. He reported having had a similar attack of flushing and circulatory collapse during the last few years, each time after drinking 3-41 of beer. Laboratory tests showed thromboplastin time 56%, partial thromboplastin time 130 s and thrombin time > 180 s. Three hours after admission the coagulation times had further deteriorated, but had become normal within 20 hours. After rest and after a provocation (hot bath) the serum concentrations were: heparin 0.21 U/ml and 0.85 U/ml; histamine 1.9 micrograms/ml and 2.3 micrograms/ml; serotonin 23 micrograms/ml and 38 micrograms/ml. Histological examination of an iliac crest bone marrow biopsy revealed dense collections of mast cells, as seen in systemic mastocytosis. A skin biopsy was diagnostic of urticaria pigmentosa.

Adult↗
PubMed1994

Stimulation of RNA polymerase II elongation by chromosomal protein HMG-14.

The high-mobility group protein 14 (HMG-14) is a non-histone chromosomal protein that is preferentially associated with transcriptionally active chromatin. To assess the effect of HMG-14 on transcription by RNA polymerase II, in vivo-assembled chromatin with elevated amounts of HMG-14 was obtained. Here it is shown that HMG-14 enhanced transcription on chromatin templates but not on DNA templates. This protein stimulated the rate of elongation by RNA polymerase II but not the level of initiation of transcription. These findings suggest that the association of HMG-14 with nucleosomes is part of the cellular process involved in the generation of transcriptionally active chromatin.

Chromatin↗