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Biomedical subjects

S Karlsson

Publications and source records attributed to S Karlsson.

At least 235 records · Page 13Linked to original sources
PubMed1986

Promoter sequences required for function of the human gamma globin gene in erythroid cells.

The human gamma- and beta-globin genes are expressed during the fetal and adult developmental periods, respectively. Differences in the sequences of their promoters may be relevant to their developmental regulation. The gamma globin gene promoter was found to be stronger than that of the beta gene. In HeLa cells co-transfected with plasmids containing the two genes, transcripts arising from the gamma promoter accumulated to a level 3-fold higher than those initiated from the beta-promoter. We have recently shown that deletion of the most distal of the conserved elements of the promoter (CACCC) reduces function to 25% of the wild-type, whereas the removal of the proximal of the two duplicated (CCAAT) elements increases promoter function 2- to 4-fold in HeLa cells during transient gene expression. Both the wild-type promoter and the truncation and linker-scanning mutants from which one of the two duplicated "CCAAT' elements had been removed, exhibited regulated expression when stably integrated into chromosomes of mouse erythroleukemia (MEL) cells. Thus, duplication of the "CCAAT' element, the feature by which the gamma promoter differs most strikingly from the beta, is not essential for function in erythroid cells.

Animals↗
PubMed1986

Stable gene transfer and tissue-specific expression of a human globin gene using adenoviral vectors.

Helper-free double recombinant adenoviruses containing a genomic human globin gene and the neomycin resistance gene (neoR) have been constructed. The inserted globin and neoR genes are stable and transcription of two human globin genes (beta and a hybrid gamma-beta gene) is correctly initiated at the respective globin promoter during lytic infection in 293 cells. The neoR gene driven by the SV40 early promoter confers G418 resistance to human fibroblasts and K562 human erythro-leukemia cells transformed with these viruses. Most neoR clones contain the entire recombinant viral genome, including the inserted globin gene, integrated into their chromosomes. Normally, K562 cells express their gamma but not their beta globin genes. The transferred human beta globin gene was not expressed in either K562 cells or fibroblasts. However, the hybrid gamma-beta globin gene was expressed in all K562 clones that contained the gene whereas gamma-beta mRNA was barely detectable in the fibroblasts. This demonstrates tissue-specific expression of the adenovirus-transferred globin gene. Furthermore, the two transferred genes, globin and neoR, which are situated more than 20 kb apart in the viral genome appear to be independently regulated.

Adenoviridae↗
PubMed1986

A clinical evaluation of fixed bridges, 10 years following insertion.

In this long-term clinical study, the condition of extensive fixed bridges was investigated 10 years after cementation. From the records of the Swedish Insurance System (Gothenburg branch) the individuals were randomly selected. All restorative treatment had been performed by private general practitioners. The investigation comprised a total of 238 bridges making 1606 units, 944 abutment and 662 pontics. Seven bridges had been removed and in a further nine cases the bridge had been separated and units removed. Loose retainers were detected at thirty (3%) abutments. In 14.5% of the surfaces a deficiency in marginal adaptation was found. An open margin seemed to be the most serious defect and was often related to caries in contact with the margin of the crown. Caries and fillings in relation to the margin were detected in 8.1% of the surfaces. Porcelain bonded to gold restorations were significantly more often overcontoured in the interproximal space compared with acrylic resin veneer gold bridges. In the investigation the caries status has been also thoroughly reported. Abutment teeth, presumed to be vital, had a prevalence of 10% radiographically visible periapical lesions. Finally, 93.3% of the bridges cemented 10 years prior to the investigation were still in function without any parts being removed.

Adult↗
PubMed1986

Gonadal steroids, gonadotropins and endometrial histology in postmenopausal women with malignant ovarian tumors.

The concentrations of FSH, LH, 17-beta-estradiol (E2), estrone (E1) and progesterone (P) were measured in peripheral and ovarian vein sera obtained at preoperative pelvic angiography from 5 postmenopausal women with malignant ovarian tumors. In 5 others the concentrations of E2, P and testosterone (T) were also measured in ascitic fluid collected at laparotomy. The investigation showed that most of these patients had increased concentrations of E2 and/or E1 and P as well in the peripheral blood. Significant gradients between the ovarian and peripheral vein concentrations were found for E2 and for P. High levels of E2, P and T were found in the ascitic fluid. FSH and LH levels were often lowered in peripheral blood compared with normal menopausal values and a gradient to ovarian tumor venous blood - with lower concentrations in the blood coming from the tumors, was found. Endometrial histology showed signs of steroid stimulation. These cases indicate that malignant ovarian tumors and/or the ovaries harboring them, are often capable of producing different sex steroids. These steroids may be found in the peripheral blood and in the ascitic fluid compartment and therefore may be used as tumor markers. The steroid production is probably not autonomous, but gonadotropin-dependent.

Adult↗
PubMed1985

Transfer of genes into hematopoietic cells using recombinant DNA viruses.

The ability of recombinant DNA viruses to transfer genes into hematopoietic cells has been explored. A recombinant simian virus 40 (SV40) in which the early region had been replaced with the chloramphenicol acetyltransferase (CAT) gene driven by the promoter from Rous sarcoma virus (RSV), was constructed. This virus transferred the CAT gene more efficiently into mouse and human bone marrow cells and into the K562, MEL, and WEHI hematopoietic tissue culture cell lines, than the classical calcium phosphate DNA transfer procedure, as shown by assay for CAT activity 48 hr after infection. Recombinant SV40 virions were also shown to be capable of stably transforming Chinese hamster ovary cells by use of an early region recombinant containing the methotrexate-resistant dihydrofolate reductase (DHFR) gene driven by the RSV promoter. The entire DHFR transcriptional unit could be detected in the genome of transformed cells that were also shown to be resistant to methotrexate. A recombinant adenovirus stock containing the neomycin-resistance gene driven by the SV40 early promoter was used to infect the K562 and MEL hematopoietic cell lines to resistance to the antibiotic G418. Transformation frequency was 10- to 100-fold higher than that obtained with calcium phosphate-precipitated DNA. Most or all of the recombinant adenovirus genome was integrated as 1-3 copies in the transformed cells. These studies show the feasibility of using DNA viruses for introduction of new genetic material into hematopoietic cells.

Acetyltransferases↗
PubMed1985

Cis-acting sequences that affect the expression of the human fetal gamma-globin genes.

We have identified the sequences in the human gamma-globin gene promoter that are required for efficient and accurate transcription by using deletion mutants and in vitro site-directed mutagenesis. More than 131 bp (which include the 'CACA' sequence) upstream from the Cap site, are required for efficient transcription of the gamma-promoter. Furthermore, the 27 bp tandemly duplicated segment including the conserved 'CCAAT' box (represented only once in the beta promoter and required for its function) is not essential for the gamma-promoter, since scanning-linker mutants lacking part or all of the proximal 'CAT' box exhibited a 1.5 to 4.0 fold increase in the promoter function compared to the wild type. These data and the recently described point mutations in the regions of the A gamma and G gamma promoters associated with hereditary persistence of fetal hemoglobin, support the notion that the DNA sequences of the gamma-promoter region should be involved in the developmental regulation of globin genes. Molecular analysis of naturally occuring deletion-mutations in the beta-globin gene cluster leading to increased production of HbF in adult life, showed that irrespective of the nature of the deletions, they exhibit identical clinical and cellular phenotypes on interaction with the beta S gene. Erythroid progenitor cells from these individuals respond in vitro, to the same extent to the modulating effects of exogenous factors such as the 'switching activity' of fetal sheep serum with respect to their pattern of hemoglobin synthesis.

Base Sequence↗
PubMed1984

Clinical, pathologic, and ultrastructural features of situs inversus and immotile-cilia syndrome in a dog.

Situs inversus, rhinitis, and bronchitis were diagnosed in a 7-month-old male Golden Retriever. Electron microscopic examination of tracheal and bronchial biopsy specimens revealed 9% of the cilia with abnormal axonemal pattern and 1.2% with a fibrous ring between the circle of microtubular doublets and the cell membrane. A permanent response to treatment with antibiotics was not obtained and the dog was euthanatized. At necropsy the thoracic and abdominal organs were found to be in reversed position. Microscopic examination revealed evidence of chronic bronchitis as well as cystic and distended distal tubules of the kidneys. Foci of fibrosis were observed in the renal cortex. The diagnosis was immotile-cilia syndrome.

Animals↗