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P Carlsson

Publications and source records attributed to P Carlsson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Solution structure and dynamics of the DNA-binding domain of the adipocyte-transcription factor FREAC-11.

Transcription factors of the forkhead type share a highly conserved DNA-binding domain of about 100 amino acid residues. FREAC-11, expressed in adipocytes, belongs to this class. Here, we report on NMR studies that established the three-dimensional structure of the FREAC-11, DNA-binding domain. Although apparent similarities to the structures of other members within the forkhead family are observed, the structure also reveals some remarkable differences. Along with the complementary dynamics, the data provide insight into the fundamentals of sequence specificity within a highly conserved motif.

Adipose Tissue↗
PubMed2000

A forkhead gene, FoxE3, is essential for lens epithelial proliferation and closure of the lens vesicle.

In the mouse mutant dysgenetic lens (dyl) the lens vesicle fails to separate from the ectoderm, causing a fusion between the lens and the cornea. Lack of a proliferating anterior lens epithelium leads to absence of secondary lens fibers and a dysplastic, cataractic lens. We report the cloning of a gene, FoxE3, encoding a forkhead/winged helix transcription factor, which is expressed in the developing lens from the start of lens placode induction and becomes restricted to the anterior proliferating cells when lens fiber differentiation begins. We show that FoxE3 is colocalized with dyl in the mouse genome, that dyl mice have mutations in the part of FoxE3 encoding the DNA-binding domain, and that these mutations cosegregate with the dyl phenotype. During embryonic development, the primordial lens epithelium is formed in an apparently normal way in dyl mutants. However, instead of the proliferation characteristic of a normal lens epithelium, the posterior of these cells fail to divide and show signs of premature differentiation, whereas the most anterior cells are eliminated by apoptosis. This implies that FoxE3 is essential for closure of the lens vesicle and is a factor that promotes survival and proliferation, while preventing differentiation, in the lens epithelium.

Amino Acid Sequence↗
PubMed2000

Forkhead transcription factor FoxF2 is expressed in mesodermal tissues involved in epithelio-mesenchymal interactions.

The growing family of forkhead transcription factors plays many important roles during embryonic development. In this study we have used in situ hybridization to explore the expression pattern of the forkhead transcription factor gene FoxF2 (FREAC-2, LUN) during mouse and rat embryogenesis, postnatal development, and in adult tissues. We demonstrate that FoxF2 is expressed in the mesenchyme adjacent to the epithelium in alimentary, respiratory, and urinary tracts, similar to FoxF1 (FREAC-1, HFH-8). FoxF2 mRNA was also observed in organs that do not express FoxF1 during embryogenesis, e.g., in the central nervous system, eye, ear, and limb buds. In organs that express both FoxF2 and FoxF1, these transcription factors may have similar functions in epithelio-mesenchymal cross-talk, but the fact that FoxF2 is more widely expressed than FoxF1 suggests that FoxF2 also has an independent role as a developmental regulator.

Age Factors↗
PubMed2000

Preoperative platelet-rich plasmapheresis and hemodilution with an autotransfusion device in total hip replacement surgery.

The effectiveness of both preoperative autologous donation (PAD) and intraoperative autotransfusion (IAT) with an autotransfusion device has recently been questioned. Preoperative apheresis, with separation of concentrated platelet rich-plasma (c-PRP) and erythrocyte concentrate (ERC), represents an aggressive use of the autotransfusion device. Can such a procedure replace PAD in total hip replacement surgery (THR)? Eighty patients undergoing THR were investigated in a prospective and randomized study. Forty patients underwent PAD, and 2 units of ERC + plasma were retrieved within 4 weeks preoperatively. Another 40 patients underwent an immediately preoperative apheresis with a concomitant hemodilution with 4% albumin, retrieving c-PRP (30% of the platelet pool) and 2 units of ERC. Both groups used IAT up to 2 hours postoperatively, with 3% dextran-60 as a plasma substitute according to our standard of care. There were no differences in blood loss, B-hemoglobin or allogeneic transfusions between the groups: 85% of the patients did not receive allogeneic blood. Both apheresis and reinfusion of c-PRP had minor impact on the coagulation parameters. Platelet count increased slightly but significantly (P<0.05) from 154 to 179 x 10(9)/L after the c-PRP at wound closure. Preoperative apheresis with an autotransfusion device, separating platelet-rich plasma and erythrocyte concentrate, is a useful alternative for patients who are unable to utilize the PAD technique for either religious or practical reasons.

Aged↗
PubMed2000

Health technology assessment in Sweden.

Sweden has a welfare system that is based on the fundamental principle that all citizens are entitled to good health and medical care, regardless of where they live or what their economic circumstances are. Health and medical care are considered to be public sector responsibilities. However, there is growing interest in establishing more private alternatives to public care. An important characteristic of the Swedish healthcare system is its decentralization, with a major role for county councils. County councils are now merging into larger administrative units (region). The whole Swedish system is in the process of reform, mainly because of perceptions that it was too rigid and had insufficient patient orientation. An important factor in the reforms is that power in the system will be even more decentralized and will have greater public input. This change is seen as calling for increased central follow-up and evaluation of matters such as social, ethical, and economic aspects. Although the state has decentralized control, it still attempts to control the general direction of the system through regulation, subsidy, recommendations, and guidelines. An important actor in the system is the Swedish Council on Technology Assessment in Health Care (SBU). SBU began in 1987 with assessments of health technologies, but its success has recently led policy makers to extend its coverage to dental care. Health technology assessment is increasingly visible to policy makers, who find it useful in decision making.

Delivery of Health Care↗
PubMed2000

Follow-up of prostate cancer patients by on-demand contacts with a specialist nurse: a randomized study.

OBJECTIVE: The effectiveness of traditional follow-up programs and the intensive search for disease progression in men with prostate cancer have been questioned. The aims of this randomized multi-centre study were to evaluate medical safety, patient satisfaction and resource utilization in an on-demand follow-up by a specialist nurse compared with traditional follow-up by a urologist. MATERIAL AND METHODS: Four hundred consecutively approached men with newly diagnosed or previously known prostate cancer in any stage at three hospitals in Sweden were randomized to follow-up in the nurse group (NG, 200 patients) or the urologist group (UG, 200 patients). In the NG, the nurse contacted the patient by phone every 6 months unless the patient himself initiated the contact. Patient satisfaction was evaluated twice a year via questionnaire. The questionnaire included the validated Hospital Anxiety and Depression Scale (HADS). The costs of all medical interventions and adverse events related to prostate cancer were calculated for all patients. RESULTS: Medical safety, measured as complication frequency and lag time from symptoms to intervention, during the first 3 years of the observation period, was similar in the NG and the UG. The total number of interventions due to symptoms from prostate cancer was also similar in both groups. The analysis of accessibility and the HAD scale showed no significant differences between the groups. The mean outpatient cost (excluding pharmaceutical costs) per patient was lower in the NG compared to the UG, especially among patients without metastases at inclusion (37% lower cost). CONCLUSIONS: Our study indicates that men with prostate cancer can be safely followed up by a specialist nurse. The study results show that this alternative follow-up is cost-effective, especially in men without metastases.

Aged↗
PubMed1999

The kidney-expressed winged helix transcription factor FREAC-4 is regulated by Ets-1. A possible role in kidney development.

In this paper we show that the kidney-expressed winged helix transcription factor FREAC-4 is regulated by Ets-1, another kidney-expressed transcription factor. Through transfection experiments three Ets-1 cis-elements are identified within the first 152 nucleotides upstream of the transcription start in the freac-4 promoter. These sites are confirmed in a DNase I in vitro protection assay using recombinant Ets-1 protein. In cotransfection experiments using an Ets-1 expression vector, the induction of freac-4 reporter gene activity is attenuated approximately 6-fold when the three Ets-1 binding sites are mutated. Furthermore, we demonstrate that overexpression of Ets-1 in the human embryonic kidney cell line 293 is sufficient to increase freac-4 mRNA levels. These results are compatible with the hypothesis that Ets-1 acts as an upstream regulator of FREAC-4 expression during kidney development.

Animals↗
PubMed1999

Transcriptional regulation of pig lactase-phlorizin hydrolase: involvement of HNF-1 and FREACs.

BACKGROUND & AIMS: One-kilobase sequence of the upstream fragment of the pig lactase-phlorizin hydrolase gene has been shown to control small intestinal-specific expression and postweaning decline of lactase-phlorizin hydrolase in transgenic mice. The aim of this study was to identify the regulatory DNA elements and transcription factors controlling lactase-phlorizin hydrolase expression. METHODS: The activity of different lactase-phlorizin hydrolase promoter fragments was investigated by transfection experiments using Caco-2 cells. Electrophoretic mobility shift assays and supershift analyses were used to characterize the interaction between intestinal transcription factors and the identified regulatory elements. RESULTS: Functional analysis revealed three previously undescribed regulatory regions in the lactase-phlorizin hydrolase promoter: a putative enhancer between -894 and -798 binding hepatocyte nuclear factor (HNF)-1 at position -894 to -880; a repressor-binding element between -278 to -264 to which an HNF-3-like factor is able to bind; and an element between -178 to -164 that binds an activating transcription factor. CONCLUSIONS: Identification of three new regulatory regions and HNF-1 and HNF-3-like transcription factor as players in the regulation of lactase-phlorizin hydrolase gene transcription has an impact on the understanding of the molecular mechanisms behind age-dependent, tissue-specific, differentiation-dependent, and regional regulation of expression in the intestine.

Animals↗
PubMed1999

Cost consciousness among anaesthetic staff.

BACKGROUND: Anaesthetists, like all other specialists, need to be aware of the costs of drugs, fluids and disposables commonly used in their clinical practice so that excessive costs and waste can be minimized without compromising patient care or safety. The present study describes cost consciousness among 120 anaesthetic staff members in two Danish anaesthetic departments. METHOD: A prospective study questioning 120 anaesthetic staff members (69 anaesthetic nurses, 35 senior anaesthetists and 16 junior anaesthetists) about the costs of 29 drugs, fluids and disposable used in routine anaesthetic practice. RESULTS: After the study period 107 questionnaires (90%) were available for analysis. Thirty-eight percent of all estimated costs were within 50% of the actual costs and 85% were within 100%. The costs of relatively expensive items such as isoflurane, enflurane, sevoflurane and hydroxyethyl starch were consistently underestimated, whereas cheaper items such as narcotic drugs, endotracheal tubes, intravenous tubing, plastic syringes and Quincke spinal needle were consistently overestimated. In general, the anaesthetic staff overestimated the costs by 69% (range -24% to 270%). The anaesthetic nursing group overestimated the costs by 49% (range -24% to 270%), junior anaesthetists by 94% (range 25% to 226%) and senior anaesthetists by 72% (range -14% to 135%). CONCLUSION: This study shows that the overall consciousness of the costs of anaesthetic drugs, fluids and disposables has to be improved in order to permit the staff to optimize resources.

Anesthesia↗
PubMed1999

Cost-minimisation analysis of laparoscopic and open appendicectomy.

OBJECTIVE: To compare the direct and indirect costs of laparoscopic and open appendicectomy. DESIGN: Randomised study. SETTING: University hospital, Sweden. MAIN OUTCOME MEASURES: Total costs for a defined period of time for each option. RESULTS: 102 patients were randomised and 99 were included in the final analysis. All patients had completely recovered within two months of operation. Disposable extra material used for the laparoscopic operation and longer operating time raised its median cost by SEK 912 and 1785, respectively. The mean duration of hospital stay, period off work (indirect costs), and time to complete recovery did not differ between the groups. CONCLUSION: Laparoscopic appendicectomy has higher direct costs than open operation and is not as cost-effective when the longterm outcome is the same in both groups.

Acute Disease↗
PubMed1998

The two-exon gene of the human forkhead transcription factor FREAC-2 (FKHL6) is located at 6p25.3.

The gene for the human transcription factor forkhead related activator 2 (FREAC-2; HGMW-approved symbol FKHL6) has been characterized and found to consist of two exons separated by an intron of 3.6 kb. The first exon encodes the forkhead DNA-binding domain and one of the transcriptional activation domains, AD2. The second exon contains the coding sequence corresponding to the C-terminal activation domain AD1. The full-length FREAC-2 protein is predicted to be 444 amino acids, which adds 39 amino acids to the previously published partial cDNA sequence. A 2-kb CG island is centered around the 5' end of the FREAC-2 gene. Fluorescence in situ hybridization was used to localize the human FREAC-2 gene to chromosomal position 6p24-p25, and the localization was further refined by radiation hybrid mapping to 6p25.3.

Amino Acid Sequence↗
PubMed1998

FREAC-1 contains a cell-type-specific transcriptional activation domain and is expressed in epithelial-mesenchymal interfaces.

The forkhead transcription factor FREAC-1 is a potent transcriptional activator. We have localized a transcriptional activation domain in the C-terminus of FREAC-1 and another one to a stretch of approximately 60 amino acids in the central part of the protein. While the C-terminal activation domain activates in all cell lines tested, the activation domain in the central part of the protein is functional only in cell lines derived from lung. This cell-type-specific activity is retained when the activation domain is fused to the heterologous DNA binding domain of Gal4. The human FREAC-1 gene was found to consist of two exons separated by an intron of 1.2 kb. Exon 1 encodes the forkhead DNA binding domain and the cell-type-specific activation domain. Exon 2 encodes the general activation domain. The distribution of FREAC-1 expression during embryogenesis was investigated by in situ hybridization. FREAC-1 mRNA was found in mesenchyme in immediate proximity to endodermal epithelia throughout the digestive, urinary, and respiratory tracts. Mesenchyme surrounding the notochord and adjacent to the ectodermal epithelia of the oral cavity and developing teeth also expresses FREAC-1. The pattern of FREAC-1 expression, with highest levels in the mesenchyme next to the epithelium and gradually diminishing as the distance from the epithelium increases, suggests that FREAC-1 expression is a response to epithelial paracrine signaling and that FREAC-1 may play a role in epitheliomesenchymal interactions.

Amino Acid Sequence↗
PubMed1998

The human forkhead protein FREAC-2 contains two functionally redundant activation domains and interacts with TBP and TFIIB.

Forkhead-related activator 2 (FREAC-2) is a human transcription factor expressed in lung and placenta that binds to cis-elements in several lung-specific genes. We have identified the parts of FREAC-2 responsible for trans-activation and found two functionally redundant activation domains on the C-terminal side of the DNA binding forkhead domain. Activation domain 1 consists of the most C-terminal 23 amino acids of FREAC-2 and contains a sequence motif conserved in an activation domain of another forkhead protein, FREAC-1. Activation domain 2 is built up by three synergistic subdomains in the central part of the FREAC-2 protein. FREAC-2 was shown to interact in vitro with TBP and TFIIB. The target site for FREAC-2 on TBP was localized to the N-terminal repeat in the core domain of TBP. TFIIB binds FREAC-2 close to the cleft between its two globular domains. The part of FREAC-2 that binds TBP was mapped to 21 amino acids in the C-terminal end of the forkhead domain. This sequence is well conserved among forkhead proteins, raising the possibility that interaction with TBP may be a general characteristic of this family of transcription factors. Overexpression of TFIIB potentiates activation by FREAC-2 in a manner dependent on the FREAC-2 activation domains. Nuclear localization of FREAC-2 was found to depend on sequences from both ends of the forkhead domain.

Amino Acid Sequence↗
PubMed1998

Resource costing for multinational neurologic clinical trials: methods and results.

We present the results of a multinational resource costing study for a prospective economic evaluation of a new medical technology for treatment of subarachnoid hemorrhage within a clinical trial. The study describes a framework for the collection and analysis of international resource cost data that can contribute to a consistent and accurate intercountry estimation of cost. Of the 15 countries that participated in the clinical trial, we collected cost information in the following seven: Australia, France, Germany, the UK, Italy, Spain, and Sweden. The collection of cost data in these countries was structured through the use of worksheets to provide accurate and efficient cost reporting. We converted total average costs to average variable costs and then aggregated the data to develop study unit costs. When unit costs were unavailable, we developed an index table, based on a market-basket approach, to estimate unit costs. To estimate the cost of a given procedure, the market-basket estimation process required that cost information be available for at least one country. When cost information was unavailable in all countries for a given procedure, we estimated costs using a method based on physician-work and practice-expense resource-based relative value units. Finally, we converted study unit costs to a common currency using purchasing power parity measures. Through this costing exercise we developed a set of unit costs for patient services and per diem hospital services. We conclude by discussing the implications of our costing exercise and suggest guidelines to facilitate more effective multinational costing exercises.

Australia↗
PubMed1998

Economic evaluation of screening for prostate cancer: a randomized population based programme during a 10-year period in Sweden.

Prostate cancer is a growing health problem representing considerable costs. Screening and early curative treatment may reduce morbidity and possibly prevent future escalating costs. However, population screening programmes are generally not well accepted at present due to uncertainty about whether screening for prostate cancer can result in reduced mortality. Evidence from large, randomized, controlled trials is still lacking. The objective of this study was to calculate clinical and economic consequences of general prostate cancer screening based on a limited screening trial in a Swedish community and a decision-tree model. A random selection of 1492 men (50-69 years) were invited to repeated screening in 1987. They have been examined every third year (four rounds). The other 7679 men in the population act as controls. The results show that the total incremental health care costs for prostate cancer will increase by 179 million SEK per year with screening compared to no-screening. The number of detected cases of localized cancer will increase by about 1000, which represents an additional cost of about 158,000 SEK per case. In conclusion, general screening for prostate cancer can be performed with a reasonable cost per detected localized cancer. Information on the long-term effect on life quality and cancer mortality is unknown.

Aged↗