PubMed Health⌕ Search

Biomedical subjects

P Carlsson

Publications and source records attributed to P Carlsson.

At least 19 recordsLinked to original sources
PubMed1997

Cloning and characterization of freac-9 (FKHL17), a novel kidney-expressed human forkhead gene that maps to chromosome 1p32-p34.

We describe the cloning of a near full-length cDNA of 4258 nucleotides encoding freac-9 (HGMW-approved symbol FKHL17), a novel human forkhead gene. The 5' untranslated region is unusual since it is very long, 2127 nucleotides, and contains 15 upstream AUG codons. Hybridization to a panel consisting of RNA derived from 50 different tissues showed that freac-9 is transcribed exclusively in the kidney. The kidney-derived cell lines COS-7 and 293 are shown to express freac-9. A combination of fluorescence in situ hybridization and somatic cell hybrids localizes freac-9 to the chromosomal region of 1p32-p34. The conceptual translation product predicts a protein of 372 amino acids with an N-terminal domain rich in acidic amino acids and with a high likelihood of forming an amphipatic helix, a DNA binding forkhead domain, and a C-terminal region that has a high probability of forming an amphipatic beta-sheet. The amino acid sequence of the DNA binding forkhead motif of FREAC-9 is identical to that of another forkhead protein, FREAC-4, whereas 12 substitutions are present at the nucleotide level. There are no similarities in regions outside of the DNA binding domains of FREAC-9 and FREAC-4 and since freac-4 maps to a different chromosome (5q12-q13) it is likely that an evolutionary selection has acted to maintain identical DNA binding domains between these two kidney expressed transcription factors.

Amino Acid Sequence↗
PubMed1997

Chromosome localization, sequence analysis, and expression pattern identify FKHL 18 as a novel human forkhead gene.

The forkhead gene family of transcription factors belongs to the "winged helix" class of DNA-binding proteins. Today over 40 members of this gene family have been identified. Forkhead genes have been shown to be involved in embryonic development, tumorigenesis, and direction of tissue specificity of gene expression. Here we describe a new human forkhead gene called freac-10 (HGMW-approved symbol FKHL 18). A combination of fluorescence in situ hybridization and somatic cell hybrids localizes freac-10 to the chromosomal region of 20q11.1-q11.2. Hybridization to a panel consisting of RNA derived from 50 different tissues shows that freac-10 is transcribed predominantly in the aorta, thus having a unique expression pattern compared with other forkhead genes. Sequence comparison reveals a striking similarity, over the conserved DNA binding region, to a murine forkhead gene-fkh-3. We propose, based on sequence differences in the N- and C-terminal regions of the forkhead domain and a clear difference in expression pattern between freac-10 and fkh-3, that freac-10 represents a novel member of this gene family.

Amino Acid Sequence↗
PubMed1997

Benign prostatic hyperplasia in Sweden 1987 to 1994: changing patterns of treatment, changing patterns of costs.

OBJECTIVES: To assess health care use and costs for benign prostatic hyperplasia (BPH) in Sweden from 1987 to 1994 when minimal invasive procedures, including transurethral microwave therapy (TUMT) and drugs, were introduced, in addition to conventional surgery. METHODS: Cross-sectional annual data on health care utilization based on national information systems and surveys were used for calculation of direct 1994 cost. RESULTS: The total number of men in the age group at risk for BPH was virtually constant, and the total direct health care costs for BPH treatment increased from 1987 to 1992. A slight decrease was evident for the years 1993 and 1994, notwithstanding the introduction of new ambulatory procedures in 1991 and of new drugs in 1992. The number of physician office visits changed little during the study period, although this estimate may be low. TUMT procedures were introduced rapidly but decreased; nevertheless, their share was never more than 3% of total costs. Drug sales were 15-fold those in 1992 and accounted for 12% of the total costs in 1994. Conventional transurethral resection of the prostate (TURP) operations decreased markedly after the introduction of the new treatments. CONCLUSIONS: The new treatments were adopted differently. TUMT procedures decreased as rapidly as they were introduced. Three years after the introduction of the new drugs, drug sales indicated that the number of men receiving drug treatment was greater than the annual number of men receiving TURP operations and TUMT procedures combined. Yet the total costs showed a slight decrease, mainly due to the decreasing numbers of TURP operations.

Aged↗
PubMed1997

How is quality of life in prostate cancer patients influenced by modern treatment? The Wallenberg Symposium.

OBJECTIVES: To identify complications of various forms of treatments for prostate cancer and their influence on patients' quality of life with the ultimate goal of suggesting a Quality of Life Questionnaire specific for prostate cancer for further validation. METHODS: The literature was screened for reports on the more common complications following various forms of therapy for prostate cancer. Frequencies were summarized. The scarce literature reporting on quality of life in prostate cancer was reviewed and conflicting data were discussed and reassessed. Suggested questionnaires used in other studies were critically scrutinized and the various questions recorded. RESULTS: Following radical surgery, impotence and incontinence were the most common complications reducing patients' quality of life. The literature was not uniform with regard to whether loss of sexual function was regarded as a worse complication than loss of urinary control. Following radiotherapy, intestinal problems and sexual dysfunction were the dominating side effects. Quality of life was best preserved in surveillance-only series. Following endocrine therapy, not only impotence and hot flushes were focused upon, but also mental dysfunction and intestinal dysfunction from nonsteroidal antiandrogens, additionally, the importance of effective palliation was highlighted. A Quality of Life Questionnaire should contain general domains relevant to cancer patients, cancer-specific questions, and prostate-cancer-specific questions. The latter group includes: worry for prostate cancer and its prognosis, bone/pelvic pain, lower urinary tract symptoms, urinary incontinence, urinary diversion, bowel function, sexual function, endocrine effects, and satisfaction with medical care for prostate cancer. CONCLUSIONS: A modern trial of prostate cancer treatment should be regarded as insufficient without including a validated Quality of Life Questionnaire.

Costs and Cost Analysis↗
PubMed1997

Surgical outcome and cost-minimisation-analyses of laparoscopic and open hernia repair: a randomised prospective trial with one year follow up.

OBJECTIVE: To compare outcome and costs between laparoscopic and open hernia repair. DESIGN: Prospective randomised study. SETTING: One university and two district hospitals in Sweden. SUBJECTS: 200 men aged 25-75 years. MAIN OUTCOME MEASURES: Operating time, hospital stay, complications, and time to recovery. A cost-minimisation-analysis was used in which the total costs were calculated for a defined period of time for each option. RESULT: The one year follow-up rate was 98%. Mean (SD) operation times in the laparoscopic and open groups were 72 (30) and 62 (25) minutes, respectively (p = 0.009). Hospital stay and complication rates did not differ between the groups. Among employees the mean (SD) periods off work in the laparoscopic and open groups were 10 (8) and 23 (21) days, respectively (p = 0.0001). The mean direct costs of the laparoscopic operation were increased by SEK 4037 (US$ 483) but the savings in indirect costs resulting from earlier return to work were SEK 11392 (US$ 1364). CONCLUSIONS: Laparoscopic hernia repair gave the employed patients faster recovery and return to work, and was the most cost-effective strategy provided that both direct and indirect costs were included.

Adult↗
PubMed1996

Characterization of the human forkhead gene FREAC-4. Evidence for regulation by Wilms' tumor suppressor gene (WT-1) and p53.

We describe the cloning and sequence analysis of a nearly full-length cDNA as well as a corresponding 5.2-kilobase pair genomic fragment encoding FREAC-4, a member of the forkhead family of transcription factors. The cDNA is collinear with respect to the coding region of the intronless genomic clone. The conceptual translation product predicts a protein of 465 amino acids with a hyperacidic amino-terminal end, a DNA binding forkhead domain and a carboxyl-terminal part that is rich in homopolymeric runs of prolines and alanines. The transcription start is identified using an RNase protection assay. A 2.7-kilobase pair genomic DNA fragment, located immediately upstream of the translation start, was fused to a luciferase reporter gene. Significant levels of luciferase activity were detected when this construct was transfected into two kidney-derived cell lines, 293 and COS-7 cells, whereas only background reporter gene expression was observed in a cell line of nonkidney origin. Cotransfections with plasmids expressing WT-1, WTAR (a mutated form of WT-1), p53, and a mutated form of p53 revealed a complex pattern of regulation with a 3-fold induction with WT-1, a 7-fold induction with mutated p53, and a 4-fold repression with wild-type p53. A 5'-promoter deletion series delimits a DNA fragment necessary for WT-1 inducibility in cotransfection experiments. This fragment is shown to contain at least one cis-element that is capable of interacting with recombinant WT-1.

Amino Acid Sequence↗
PubMed1996

Differential activation of lung-specific genes by two forkhead proteins, FREAC-1 and FREAC-2.

We describe the cDNA sequences for two human transcription factors, Forkhead RElated ACtivator (FREAC)-1 and -2, that belong to the forkhead family of eukaryotic DNA binding proteins. FREAC-1 and -2 are encoded by distinct genes, are almost identical within their DNA binding domains and in the COOH termini, but are otherwise divergent. Cotransfections with a reporter carrying FREAC binding sites showed that both proteins are transcriptional activators, and deletions located the activation domains to the COOH-terminal side of the forkhead domains. Expression of FREAC-1 and FREAC-2 is restricted to lung and placenta. We show that the promoters of genes for lung-specific proteins such as pulmonary surfactant proteins A, B, and C (SPA, SPB, and SPC) and the Clara cell 10-kDa protein (CC10) contain potential binding sites for FREAC-1 and FREAC-2. DNaseI footprinting verified that FREAC proteins bind to the predicted sites in the CC10 and SPB promoters. While an SPB promoter construct could be transactivated by both FREAC-1 and FREAC-2, CC10 was only activated by FREAC-1. Efficient activation of CC10 by FREAC-1 is shown to be specific for a lung cell line with Clara cell characteristics (H441) and to involve a region of the FREAC-1 protein unable to activate in other cell types.

Amino Acid Sequence↗
PubMed1996

Linearity of sound transmission through the human skull in vivo.

The linearity of sound propagation through the human skull was investigated. One male subject, equipped with bilateral skin-penetrating titanium fixtures for attachment of bone-anchored hearing aids, was studied thoroughly. Three different methods were used: comparison of the frequency response functions estimated at different signal levels (using stepped sine as well as random noise), comparison of the coherence function at different signal levels (using random noise), and the Hilbert transform of the estimated frequency response function. Frequencies from 0.1 to 10 kHz and signal levels up to 77 dB HL at discrete frequencies were used. No indication of any significant nonlinear behavior was found with the three methods used.

Bone Conduction↗
PubMed1996

An estimate of the life-time cost of surgical treatment of patients with benign prostatic hyperplasia in Sweden.

Two clinical series (n = 96 + 90) and one record-linkage study (n = 492) were used for estimation of the health care utilization for the treatment of BPH patients, mainly by TURP, in Sweden during one year before and 5-7 years after surgery. The total cost for a single patient amounted to ca. 33000 SEK in 1900 prices (5850 USD). Costs for surgery dominated and for a TURP amounted to about 70% of the Total. The costs during one year preoperatively and 5 years postoperatively each amounted to 15% of the total costs. In the present study the outcome of surgery was similar to other reports from the same period. The surgical mortality was 0.4% and the readmission rate because of complications of surgery or manifestations of BPH was 25% after 7 years of observation. Of the patients 11% were reoperated on within 7 years. When transurethral resection of the prostate (TURP) replaced open surgery in Sweden during the 1970's it had several of the attributes of the new methods introduced for treatment of benign prostate hyperplasia (BPH) currently in use. However, the spread of TURP resulted in wider indications for surgery and an increase in the total number of surgical procedures. An important argument for the adoption of the new, less invasive methods for treatment of BPH is the lower cost. To make a fair comparison of the costs of different methods for treatment of BPH the long-term costs have to be included in the calculation.

Aged↗
PubMed1996

Extracorporeal shock-wave lithotripsy of gallbladder stones: an alternative for the selected few.

OBJECTIVE: To define selection criteria for optimal outcome of ESWL with oral litholysis (ursodeoxycholic acid) for gallbladder stones. DESIGN: Prospective study. SETTING: University hospital, Sweden. SUBJECTS: 145 patients with symptomatic gallbladder stones occupying a maximum of half the fasting gallbladder volume and gallbladder opacification at oral cholecystography. MAIN OUTCOME MEASURES: Three-year stone clearance rates in relation to initial stone burden, occurrence of calcified stones, and degree of gallbladder opacification at cholecystography. RESULTS: At all times clearance rates according to life table analysis were significantly higher for patients whose stone volume was < or = 4.2 ml (corresponding to one stone with a diameter of < or = 2.0 cm) (83% at 3 years) than for patients whose stone volume was > 4.2 ml (67% at 3 years), and patients with one stone had significantly higher clearance rates (88% at 3 years) than patients with multiple stones (58% at 3 years). Of all patients treated for gallbladder stones during one year, 25/194 (13%) had a stone volume of < or = 4.2 ml and 16/194 (8%) a solitary stone with volume < or = 4.2 ml. Neither the degree of gallbladder opacification nor the occurrence of calcified stones influenced clearance rates. CONCLUSION: ESWL may be an alternative to surgery in the few patients whose stone volume is roughly 4 ml or less and preferably have only one stone. Gallbladder function and patency of the cystic duct are poorly evaluated by oral cholecystography.

Adult↗
PubMed1995

Chromosomal localization of six human forkhead genes, freac-1 (FKHL5), -3 (FKHL7), -4 (FKHL8), -5 (FKHL9), -6 (FKHL10), and -8 (FKHL12).

The forkhead family of transcription factors has been shown to be involved in the regulation of embryonic development in organisms from Drosophila to humans. Genes encoding forkhead proteins are also emerging as a new class of oncogenes with relevance for human cancer. We have used a combination of fluorescence in situ hybridization and somatic cell hybrids to map the chromosomal localizations of five previously cloned human forkhead genes, freac-1, -3, -4, -5, and -6. (HGMW-approved symbols FKHL5, FKHL7, FKHL8, FKHL9 and FKHL10). We also report the sequence and the chromosomal position of a novel human forkhead gene, freac-8 (FKHL12). The freac genes have been localized to the following positions: freac-1, 16q24; freac-3, 6p25; freac-4, 5q12-q13; freac-5, 9 pericen; freac-6, 5q34, and freac-8, 1p32.

Amino Acid Sequence↗
PubMed1995

Selection of high-affinity binding sites for sequence-specific, DNA binding proteins from random sequence oligonucleotides.

We describe a rapid and sensitive method to isolate sets of high-affinity binding sites for sequence-specific DNA binding proteins. The DNA binding domain of the protein is expressed in Escherichia coli as a fusion with glutathione S-transferase (GST). Binding reactions are set up with total soluble extract from induced bacteria and a double-stranded oligonucleotide for which the central 32 bp have been randomized. To ensure stringent conditions, binding is done in the presence of high levels of poly(dI:C). The GST fusion protein is recovered by the addition of glutathione-Sepharose. Following extensive washing of the Sepharose beads, the bound oligonucleotides are rescued by polymerase chain reaction amplification. The amplified material is used in the next cycle of selection and amplification. Approximately five cycles are needed to obtain a pure population of high-affinity sites, which are then cloned and sequenced. This procedure should be applicable to any sequence-specific DNA binding protein for which the cDNA is available and which can be expressed in bacteria in a functional form.

Base Sequence↗
PubMed1995

Cost-effectiveness analysis in early detection of prostate cancer: an evaluation of six screening strategies in a randomly selected population of 2,400 men.

Based on the findings in an early detection study for prostate cancer [Gustafsson et al.: J Urol 148:1827-1831, 1992] using digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate-specific antigen (PSA), a cost-effectiveness analysis was performed based on 6 screening strategies, namely: 1) DRE of all individuals; 2) TRUS of all individuals; 3) DRE, TRUS, and PSA analysis followed by reexamination of individuals with PSAs > or = 7 ng/ml; 4) DRE of individuals with PSAs of > or = 4 ng/ml; 5) TRUS of individuals with PSAs of > or = 4 ng/ml; 6) DRE and PSA analysis followed by TRUS on individuals with PSAs > or = 4 ng/ml. The detection rates of prostate cancer using these 6 strategies were 2.4%, 3.3%, 3.6%, 2.0%, 2.6%, and 3.2%, respectively. Except for costs per detected cancer, costs were also calculated per detected small cancer (< or = 1.5 cm) and per detected cancer treated for cure. The cost calculations were based on total costs, i.e., direct plus indirect costs. When the 6 strategies were compared, taking into account the detection rate of cancers treated for cure and cost-effectiveness with respect to cancers treated for cure, strategies 1), 2), 3), and 4) were ruled out as less favorable than the remaining 2 strategies. TRUS of individuals with PSAs > or = 4 ng/ml (strategy 5) was the most cost-effective strategy and detected 80% of the cancers actually treated for cure. Screening with DRE and PSA analysis followed by TRUS of individuals with PSAs > or = 4 ng/ml (strategy 6) had a somewhat lower cost-effectiveness, but detected 90% of the cancers treated for cure.

Aged↗