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Biomedical subjects

A Wedel

Publications and source records attributed to A Wedel.

At least 19 recordsLinked to original sources
PubMed2001

Dentists' perception of risks for molars without antagonists. A questionnaire study of dentists in Sweden.

The aim of this questionnaire study was to investigate dentists' assessment of and the decision making process in a clinical situation with unopposed molar teeth. The questionnaire comprised, besides questions about the dentist's background, a presentation of a clinical situation with a 42-year old male patient who just had lost the left mandibular molars (teeth 36 and 37). A series of questions was provided with multiple choice answers regarding what most probably would occur with the unopposed maxillary molars within a 10-year period, what treatment to propose in such a situation, and indications for the proposed treatment. The questionnaire was sent to a randomly selected group of active members of the Göteborg Dental Society. Two hundred completed questionnaires were returned (response rate 72.5%). The great majority (85%) suggested that marked overeruption of the unopposed molars would occur, whereas 13% believed in minor changes. Almost half of the respondents (47%) proposed to wait and see before any treatment was started, whereas the remaining dentists wanted to perform some therapy as soon as possible or within a specified period of time. The most commonly suggested indications for treatment were risk for overeruption (79%), risk for impaired masticatory function (54%), and risk for development of TMD (50%). Differences in answers were found between female and male dentists, between specialists and general practitioners, and with respect to year of graduation. Most dentists believed that overeruption would occur in spite of the limited knowledge of what will happen to unopposed teeth.

Adult↗
PubMed2000

Role of Stat3 in lipopolysaccharide-induced IL-10 gene expression.

IL-10 is a unique cytokine because it is anti-inflammatory and immunosuppressive. IL-10 is regulated at the level of transcription, but the critical motifs and the relevant transcription factors controlling this gene have remained elusive to date. We now report that a sequence at -120 bp in the human IL-10 promoter binds Stat3 but no other Stat proteins. Mutation of this motif abrogates LPS-induced trans-activation. Overexpression of dominant negative Stat3 suppresses promoter activity, while wild-type Stat3 leads to an enhancement of this activity. Our results show that Stat3, by binding to a single motif in the IL-10 promoter, is controlling expression of the human IL-10 gene.

Cell Line↗
PubMed1999

Role of p52 (NF-kappaB2) in LPS tolerance in a human B cell line.

Cells of the weakly CD14 positive human B cell line RPMI 8226, clone 1, will mobilize NF-kappaB (p50/p65 and p50/p50) proteins and produce TNF mRNA when stimulated with lipopolysaccharide (LPS). When such cells are precultured with a low amount of LPS (50-250 ng/ml) for 3 - 4 days followed by a secondary stimulation with a high dose of LPS (1 microg/ml) then the cytokine expression is strongly reduced, i. e. the cells have become tolerant. Western blot analysis of proteins of the NF-kappaB/rel family demonstrates cytoplasmic p50 and p65 for naive B cells plus a low level of p52. While with tolerance induction the pattern of p50 and p65 proteins remains essentially unchanged, the LPS tolerant 8226 cells show a dramatic increase of both p52 protein and its p100 precursor in the cytosol. This p52 is found strongly upregulated in Western blots of extracts from purified nuclei of tolerant cells. Also, gelshift analysis with the -605 kappaB motif of the human TNF 5'-region shows an additional high mobility complex in LPS tolerant cells -a complex that is supershifted with an anti-p52 antibody. Functional analysis with the -1064 TNF 5'-region in front of the luciferase reporter gene demonstrates that transactivation of the TNF promoter is strongly reduced in tolerant cells. Also, overexpression of p52 will suppress activity of TNF promoter reporter gene constructs. Taken together these data show that tolerance to LPS in the human RPMI 8226 B cell line involves upregulation of the p52 (NF-kappaB2) gene, which appears to be instrumental in the blockade of TNF gene expression.

B-Lymphocytes↗
PubMed1998

Tooth wear and temporomandibular joint morphology in a skull material from the 17th century.

Skeletal remnants from the skulls of 69 subjects from the 17th century have been studied focusing on TMJ morphology and tooth wear. Several of the skulls were damaged and altogether 68 condyles and 28 temporal components of the TMJ, and 97 dentate jaws could be examined. Tooth wear was extensive and most of the first molars in both jaws had lost most of their occlusal morphology. This is remarkable with respect to the fact that the great majority of the subjects had died before the age of 35 years, according to the age determination performed. The TMJs showed frequent remodelling but only rarely deformative changes. The frequent observation of a broken up compact bone layer on the condyle was interpreted as a post-mortem artefact. The results indicate adaptive response of the TMJs to the probably heavy masticatory function but do not support the suggested relationship between tooth wear and TMJ osteoarthrosis.

Age Determination by Teeth↗
PubMed1996

CCAAT/enhancer binding protein is involved in the expression of the tumour necrosis factor gene in human monocytes.

Within the human TNF promoter we have identified two sites at positions -189 and -101 that show C/EBP specific binding of nuclear proteins from cells of the human monocytic line Mono Mac 6. Supershift analysis with anti C/EBP antibodies revealed that the complexes formed consist of both C/EBP alpha and C/EBP beta. When studying reporter constructs with a 5'-deletion series of the TNF promoter in cotransfection experiments with a C/EBP beta expression plasmid, a construct with the -1064 TNF fragment gave 26-fold transactivation, the -630 fragment showed 23-fold transactivation and the -107 fragment (containing the -101 C/EBP binding motif) still gave 16-fold transactivation. Mutagenesis of the -101 site in the -630 construct resulted in a reduction of C/EBP driven transactivation from 26-fold to 7-fold. Finally, when Mono Mac 6 cells were transfected with these constructs, stimulation by LPS induced a 19-fold transactivation in the -630 wild type construct, while the -630 construct carrying the -101 mutation was transactivated only 4-fold. Hence, the data indicate that the -101 C/EBP motif is crucial for TNF gene expression in human monocytes.

CCAAT-Enhancer-Binding Proteins↗
PubMed1995

The bacterial enhancer-binding protein NTRC is a molecular machine: ATP hydrolysis is coupled to transcriptional activation.

NTRC is a prokaryotic enhancer-binding protein that activates transcription by sigma 54-holoenzyme. NTRC has an ATPase activity that is required for transcriptional activation, specifically for isomerization of closed complexes between sigma 54-holoenzyme and a promoter to open complexes. In the absence of ATP hydrolysis, there is known to be a kinetic barrier to open complex formation (i.e., the reaction proceeds so slowly that the polymerase synthesizes essentially no transcripts even from a supercoiled template). We show here that open complex formation is also thermodynamically unfavorable. In the absence of ATP hydrolysis the position of equilibrium between closed and open complexes favors the closed ones. Use of linear templates with a region of heteroduplex around the transcriptional start site--"preopened" templates--does not bypass the requirement for either NTRC or ATP hydrolysis, providing evidence that the rate-limiting step in open complex formation does not lie in DNA strand denaturation per se. These results are in contrast to recent findings regarding the ATP requirement for initiation of transcription by eukaryotic RNA polymerase II; in the latter case, the ATP requirement is circumvented by use of a supercoiled plasmid template or a preopened linear template.

Adenosine Triphosphate↗
PubMed1995

In vitro transcription close to the melting point of DNA: analysis of Thermotoga maritima RNA polymerase-promoter complexes at 75 degrees C using chemical probes.

The interaction of DNA dependent RNA polymerase of the extreme thermophile bacteria Thermotoga maritima with a promoter bearing DNA fragment was investigated in the temperature range from 20 to 85 degrees C. We show that the T. maritima RNA polymerase recognizes and utilizes the Escherichia coli T7 A1 promoter with an efficiency similar to that of the E. coli polymerase. We have investigated the interaction of both polymerases with the same promoter over a wide range of temperatures using hydroxyl radical foot-printing and osmium tetroxide probing. This study revealed that the T. maritima polymerase goes through a series of isomerisation events very similar to the E. coli polymerase, i.e. the closed, intermediate and open complexes, but the transitions themselves occur at radically different temperatures. This indicates that conformational changes in the DNA that accompany initiation of transcription such as promoter melting are determined by the polymerase rather than the DNA sequence.

2,2'-Dipyridyl↗
PubMed1995

The C/EBP family of transcription factors.

The C/EBP proteins form a family of transcription factors with at least seven members. These proteins consist of three structural components which include a C-terminal leucine-zipper, a basic DNA-binding region and a N-terminal transactivating region. Dimerization through the leucine-zipper leads to formation of homo- and heterodimers which then bind with their two basic regions to often non-symmetric DNA-sequences in the promoter/enhancer regions of a variety of genes. Expression of C/EBP is prominent in adipocytes, hepatocytes and monocytes/macrophages, and here these proteins are involved in tissue-specific gene expression. Target genes for C/EBP include those for acute phase response genes in liver cells and for cytokine genes in monocytes/macrophages. Therefore, intervention at the level of C/EBP transcription factors may prove effective in controlling immune response.

Animals↗
PubMed1995

Tolerance to lipopolysaccharide in human blood monocytes.

When monocytes are stimulated with Lipopolysaccharide (LPS), they efficiently produce cytokines like tumor necrosis factor (TNF). Upon secondary stimulation, this response is only minimal, and there is little TNF mRNA transcription, mRNA accumulation, and protein production. Studies with the monocytic cell line Mono Mac 6 have shown that in such tolerant cells the CD14 LPS receptor is still present, and the transcription factor NF-kB is still efficiently mobilized. This NF-kB complex has, however, a different composition, that does not transactivate TNF promoter reportergene constructs. We now show that similar mechanisms apply to primary blood monocytes. After primary stimulation these cells also produce high levels of TNF and then develop tolerance in that upon secondary challenge little TNF is produced. CD14 cell surface expression is unchanged or even increased in tolerant cells and NF-kB mobilization does still occur. The complex mobilized in such tolerant monocytes is, however, composed mainly of high mobility binding proteins. This indicates that p50 homodimers predominate in NF-kB complex of tolerant blood monocytes, similar to what has been reported for Mono Mac 6 cells. The data add to the notion that p50 binding to the cognate -kB DNA motif in the TNF promoter may be responsible for the unresponsiveness in LPS tolerance.

Base Sequence↗
PubMed1994

Tolerance to lipopolysaccharide involves mobilization of nuclear factor kappa B with predominance of p50 homodimers.

Stimulation of the human monocytic cell line Mono Mac 6 with lipopolysaccharide (LPS) leads to rapid and transient expression of cytokines like tumor necrosis factor (TNF). When such cells are precultured for 2 days with a low dose of LPS (20 ng/ml) followed by stimulation with a high dose of LPS (1 microgram/ml), expression of the TNF gene is minimal, i.e. the cells are tolerant. In nuclear run-on analysis, such tolerant cells show only a low degree of transcription, indicating that tolerance operates at or upstream of the transcription level. The CD14 LPS receptor is, however, up-regulated (not down-regulated) in tolerant cells, and LPS can, in fact, still lead to activation of tolerant cells as evidenced by mobilization of the transcription factor nuclear factor kappa B (NF-kappa B). Resolution of the NF-kappa B complex in gel shift analysis shows that the binding protein, mobilized in naive Mono Mac 6 cells, consists mainly of p50-p65 heterodimers, while in tolerant cells, the p50 homodimer is predominant. This increase in p50 homodimers coincides with an increase in p105 mRNA, suggestive of a transcriptional up-regulation of p50. Reporter gene analysis reveals that the NF-kappa B complex mobilized in tolerant cells is functionally inactive in that NF-kappa B-dependent luciferase constructs containing the human immunodeficiency virus long terminal repeat or the TNF 5'-region show only minimal transactivation after LPS stimulation. Similar to Mono Mac 6 cells, primary blood monocytes, when precultured with a low dose of LPS, also become tolerant and produce little TNF after LPS stimulation. The tolerant blood monocytes also up-regulate CD14, and they mobilize NF-kappa B with a predominance of p50 homodimers. Taken together, these results demonstrate that tolerance to LPS is determined by post-receptor mechanisms that involve an altered composition of the NF-kappa B complex.

Antigens, CD↗
PubMed1994

Masticatory function in patients with congenital and acquired maxillofacial defects.

Ninety-eight patients who received prosthodontic treatment for maxillofacial defects were examined clinically and by means of questionnaires and registration of chewing efficiency and occlusal force. Although 30% of the patients stated that they could chew soft food, and one third could not chew the test food (almonds), only 14% said they had a poor chewing ability. The mean occlusal force was small (80 N) but the individual variation was great (median 49 N, maximum 327 N). Despite major defects and poor functional test results, most patients were remarkably well-adapted to their situation and to maxillofacial prosthodontic rehabilitation. Severe signs and symptoms of temporomandibular disorders were rare.

Adolescent↗
PubMed1994

From initiation to elongation: comparison of transcription by prokaryotic and eukaryotic RNA polymerases.

Multisubunit RNA polymerases in prokaryotes and eukaryotes share an evolutionarily conserved core. Here, we compare the processes of promoter recognition, transcription initiation and transcript elongation by human RNA polymerase II and by the RNA polymerase of the eubacterium Escherichia coli. Although these two polymerases have diverged widely in structure, important functions have been conserved, suggesting that the basic mechanisms of RNA transcription are similar in eukaryotes and prokaryotes.

DNA-Directed RNA Polymerases↗
PubMed1993

Pyrrolidine dithiocarbamate inhibits NF-kappa B mobilization and TNF production in human monocytes.

The human TNF promoter contains four potential nuclear factor-kappa B (NF-kappa B)-binding sites, with the strongest binding seen for the -605 motif. Nuclear extracts from unstimulated cells of the human monocytic cell line, Mono Mac 6, contain one specific binding protein (complex II), consistent with a constitutive p50 homodimer. Stimulation of Mono Mac 6 cells with LPS will increase complex II and will strongly induce a second specific complex (complex I), which represents the p50/65 heterodimer. Treatment of Mono Mac 6 cells with pyrrolidine-dithiocarbamate (PDTC) at 300 microM will block the LPS-induced complex I almost completely and will reduce complex II to the constitutive level. Binding activity of other nuclear factors that recognize the SP-1 and c/EBP motifs of the human TNF promoter is not affected by such treatment. Northern blot analysis demonstrates that PDTC treatment will strongly reduce LPS-induced TNF transcripts. Secreted TNF protein as detected in the Wehi 164S/ActD bioassay and in a sandwich immunoassay was similarly reduced by PDTC. Kinetic analyses show that after LPS stimulation, NF-kappa B will peak at 1 h, TNF transcript prevalence at 2 h, and TNF protein at 4 h. PDTC did not shift this response to LPS to a later time, but suppressed NF-kappa B mobilization, TNF transcripts, and TNF protein over the entire 8-h observation period. Analysis of freshly isolated, LPS-stimulated blood monocytes showed a similar blockade of NF-kappa B. Furthermore, in these primary cells, induction of TNF transcripts, as determined by Northern blot analysis and by quantitative polymerase chain reaction, was prevented by PDTC as was TNF protein production. These data show that dithiocarbamates can profoundly affect cytokine expression and suggest that NF-kappa B is involved in LPS-induced TNF gene expression in human monocytes.

Binding Sites↗
PubMed1992

The mouse M-lysozyme gene domain: identification of myeloid and differentiation specific DNasel hypersensitive sites and of a 3'-cis acting regulatory element.

The mouse M-lysozyme gene is exclusively expressed in myeloid cells of the blood system being progressively turned on upon cell differentiation. In this study the mechanism controlling this tissue- and differentiation stage-specific gene expression was analyzed at the level of chromatin structure. A complex pattern consisting of constitutive and differentiation dependent DNasel hypersensitive sites (HSs) was found in a set of various myeloid cell lines, representing different stages of maturity. The chromatin of a lymphoid cell line, which does not express the lysozyme gene, is completely insensitive to DNasel digestion. Chromatin analysis of two multipotent hematopoietic stem cell lines which can be differentiated in vitro to mature myeloid cells confirmed that these identified DNasel HSs are specific for distinct differentiation stages, rather than being a characteristic feature of the cell lines. Additionally, the stem cell studies revealed that the hypersensitivity of the chromatin domain is already established at the multipotent stage. DNA fragments spanning a cell type- and differentiation stage-specific cluster of HSs in the 3' region of the gene showed enhancer activity in all cell types tested. In the light of this lack of specificity, we suggest that cell type-specific modification of the chromatin structure in this region may play a role in determining the binding of a widespread transcription factor, and hence contribute to the time specificity of lysozyme M gene expression.

Animals↗
PubMed1992

A cross-sectional and longitudinal study of craniomandibular dysfunction in an elderly population.

Three cohorts of subjects in their 70s (born in 1901 to 1902, 1906 to 1907, and 1911 to 1912; n = 1,065) were investigated by means of questionnaires and clinical examination. The first cohort was followed to age 83 and the others to age 75. Symptoms of craniomandibular dysfunction were reported less frequently with increasing age. This was especially marked in men. Clinical signs of severe dysfunction were rare, and according to the Helkimo classification they tended to decrease with increasing age. The longitudinal results mainly confirmed the cross-sectional data. The results indicated that there is no increased risk of craniomandibular dysfunction with aging. On the contrary, awareness of such symptoms tended to decrease with aging.

Age Factors↗
PubMed1990

A bacterial enhancer functions to tether a transcriptional activator near a promoter.

The nitrogen regulatory protein NtrC of enteric bacteria activates transcription of the glnA gene by catalyzing isomerization of closed complexes between RNA polymerase and the glnA promoter to open complexes. NtrC binds to sites upstream of glnA that have properties of eukaryotic transcriptional enhancers. NtrC-binding sites were found to facilitate open complex formation when these sites and the glnA promoter were located on different rings of a singly linked catenane, but not when the two rings were decatenated. The results provide evidence that NtrC contacts RNA polymerase-promoter complexes in a process mediated by formation of a DNA loop. NtrC-binding sites serve to tether NtrC near the glnA promoter, thereby increasing the frequency of collisions between NtrC and polymerase-promoter complexes.

Bacterial Proteins↗